Radical generation catalyst, method for producing radical, method for producing oxidation reaction product, drug, and drug for agricultural and livestock products

Abstract

The purpose of the present invention is to provide a radical generation catalyst capable of generating (producing) radicals under mild conditions. In order to achieve the aforementioned purpose, the first radical generation catalyst according to the present invention is characterized by containing at least one substance selected from the group consisting of amino acids, peptides, phospholipids, and salts thereof. The second or third radical generation catalyst according to the present invention is characterized by containing an ammonium salt (excluding peroxydisulfate) having a Lewis acidity of 0.4 eV or more.

Description

[0001] This application is a divisional application based on the Chinese invention patent application with application number: 201880040160.5, application date: June 18, 2018, and invention name: "Free radical generating catalyst, method for producing free radicals, method for producing oxidation reaction products, agents and agents for agricultural and livestock production". Technical Field

[0002] The present invention relates to a free radical generating catalyst, a method for producing free radicals, a method for producing oxidation reaction products, a drug, and a drug for agricultural and livestock production. Background Art

[0003] Free radicals are rich in reactivity and are therefore important chemical species that are widely used. For example, sodium chlorite (NaClO2) is a non-toxic and inexpensive oxidizing agent that is used as a free radical chlorine dioxide (ClO2 · )'s precursor (Non-Patent Documents 1 to 4). Prior art literature Non-patent literature Non-patent document 1: H. Dodgen and H. Taube, J. Am. Chem. Soc., 1949, 71, 2501-2504. Non-patent document 2: JK Leigh, J. Rajput, and D E Richardson, Inorg. Chem., 2014, 53, 6715-6727. Non-patent document 3: CLLatshaw, Tappi, 1994, 163-166. Non-patent literature 4: (a) JJ Leddy, in Riegel's Handbook of Industrial Chemistry, 8 th edn. Ed., JA Kent, Van Nostrand Reinhold Co. Inc, New York, 1983, pp. 212-235; (b) I. Fabian, Coord. Chem. Rev., 2001, 216-217, 449-472. Summary of the invention

[0004] However, in general, a large amount of energy is required to generate free radicals, and therefore, heating to a high temperature is required, which poses problems in terms of cost and reaction control.

[0005] Therefore, the object of the present invention is to provide a free radical generating catalyst capable of generating (manufacturing) free radicals under mild conditions, a method for manufacturing free radicals using the above-mentioned free radical generating catalyst, and a method for manufacturing an oxidation reaction product using the above-mentioned free radical manufacturing method, a drug, and a drug for agricultural and livestock production.

[0006] In order to achieve the above object, the first radical generating catalyst of the present invention is characterized by comprising at least one selected from amino acids, proteins, peptides, phospholipids and salts thereof.

[0007] The second radical generating catalyst of the present invention is characterized in that it comprises an ammonium salt (excluding peroxodisulfate) represented by the following chemical formula (XI), and the Lewis acidity of the ammonium salt is 0.4 eV or more; In non-acidic liquids, catalyzes the generation of free radicals from free radical generating sources; The free radical generating source is at least one selected from halous acid, halite ion and halite salt, In the above chemical formula (XI), R 11 , R 21 , R 31 and R 41 Each is a hydrogen atom or an aromatic ring, or an alkyl group, the alkyl group may contain an ether bond, a carbonyl group, an ester bond or an amide bond, or an aromatic ring, R 11 , R 21 , R 31 and R 41 They can be the same or different. Or, R 11 , R 21 , R 31 and R 41 Two or more of them can be integrated and bonded to N + Together they form a ring structure, which may be a saturated ring structure or an unsaturated ring structure, may be an aromatic ring or a non-aromatic ring, and may or may not have one or more substituents; X - It is an anion (excluding peroxydisulfate).

[0008] The third radical generating catalyst of the present invention is characterized in that it comprises an ammonium salt represented by the following chemical formula (XI), and the Lewis acidity of the ammonium salt is 0.4 eV or more; catalyzing the generation of free radicals from a free radical generating source in the presence of an oxidizing agent; The above oxidant is O2; The free radical generating source is selected from a nitrogen-containing aromatic cation derivative represented by any one of the following formulas (A-1) to (A-8), a 9-substituted acridine represented by the following formula (A-9) ion, quinoline represented by the following formula (I) ionic derivatives, their stereoisomers and tautomers, and at least one of their salts, In the above chemical formula (XI), R 11 , R 21 , R 31 and R 41 Each is a hydrogen atom or an aromatic ring, or an alkyl group, the alkyl group may contain an ether bond, a carbonyl group, an ester bond, an amide bond, or an aromatic ring, R 11 , R 21 , R 31 and R 41 They can be the same or different. Or, R 11 , R 21 , R 31 and R 41 Two or more of them can be integrated and bonded to N + Together they form a ring structure, which may be a saturated ring structure or an unsaturated ring structure, may be an aromatic ring or a non-aromatic ring, and may or may not have one or more substituents; X - It is an anion; In the above formulas (A-1) to (A-8) and (A-9), R is a hydrogen atom or any substituent; Ar is the above electron donating group, which may be one or more, and in the case of multiple electron donating groups, they may be the same or different; The nitrogen-containing aromatic ring forming the nitrogen-containing aromatic cation may have one or more arbitrary substituents other than R and Ar, or may not have one or more arbitrary substituents other than R and Ar; In the above formula (I), R 1 is a hydrogen atom or any substituent; Ar 1 ~Ar 3 Each is a hydrogen atom or the above electron-donating group, which may be the same or different. Ar 1 ~Ar 3At least one of the above-mentioned electron-donating groups is an electron-donating group.

[0009] In addition, hereinafter, the first radical generating catalyst in the present invention, the second radical generating catalyst in the present invention, and the third radical generating catalyst in the present invention may be collectively referred to as "the radical generating catalyst of the present invention".

[0010] In order to achieve the above object, the first method for producing radicals in the present invention is characterized by comprising a mixing step of mixing the radical generating catalyst of the present invention and a radical generating source.

[0011] The method for producing the second radical in the present invention is characterized by comprising: A mixing step of mixing a Lewis acid (excluding peroxodisulfate) having a Lewis acidity of 0.4 eV or more and a free radical generating source; and A reaction step of reacting the Lewis acid with the free radical generating source in a non-acidic liquid; The free radical generating source is at least one selected from halous acid, halite ion and halite salt.

[0012] The method for producing the third radical in the present invention is characterized by comprising: A mixing step of mixing a Lewis acid having a Lewis acidity of 0.4 eV or more, O2, and a free radical generating source; and A reaction step of allowing the Lewis acid, the O2 and the free radical generating source to react in a liquid; The above-mentioned Lewis acid is the third free radical generating catalyst in the present invention; The free radical generating source is selected from a nitrogen-containing aromatic cation derivative represented by any one of the above formulas (A-1) to (A-8), a 9-substituted acridine represented by the above formula (A-9), ion, quinoline represented by the above formula (I) ionic derivatives, their stereoisomers and tautomers, and at least one of their salts.

[0013] The method for producing the fourth radical in the present invention is characterized by comprising: a mixing step of mixing a Lewis acid (excluding peroxodisulfate) having a Lewis acidity of 0.4 eV or more and a radical generating source; and A reaction step of reacting the Lewis acid and the free radical generating source in a liquid; The Lewis acid having a Lewis acidity of 0.4 eV or more contains an inorganic substance; The free radical generating source is at least one selected from halous acid, halite ion and halite salt.

[0014] It should be noted that, hereinafter, the method for producing the first free radical in the present invention, the method for producing the second free radical in the present invention, the method for producing the third free radical in the present invention, and the method for producing the fourth free radical in the present invention are sometimes collectively referred to as the "method for producing free radicals of the present invention."

[0015] In addition, the method for producing an oxidation reaction product of the present invention is a method for producing an oxidation reaction product by oxidizing an oxide, characterized in that it comprises: a free radical production step of producing the free radical by the free radical production method of the present invention; and An oxidation reaction step of causing the oxidized substance to react with an oxidant by the action of the free radicals to generate the oxidation reaction product.

[0016] The medicament of the present invention is characterized by comprising: Free radical generating catalysts and free radical generating sources; The radical generating catalyst is the radical generating catalyst of the present invention.

[0017] The agricultural and livestock medicine of the present invention is characterized by comprising: Free radical generating catalysts and free radical generating sources; The radical generating catalyst is the radical generating catalyst of the present invention. Effects of the Invention

[0018] According to the manufacture method of free radical generation catalyst of the present invention, free radical generator and free radical, can produce (manufacture) free radical under mild condition. As the purposes of the manufacture method of free radical generation catalyst of the present invention, free radical generator and free radical, for example, can be used for the manufacture method of above-mentioned oxidation reaction product of the present invention, but is not particularly limited thereto, can be used for a wide range of purposes. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1 UV+Vis absorption spectra of NaClO2 (5.0 mM) collected at 0, 4, and 16 h after mixing with Sc(OTf)3 (10 mM) in aqueous solution at 298 K. Figure 2 (a) is the reaction of Sc(OTf)3 (10 mM) and NaClO2 (5.0 mM) in aqueous solution (0.20 M acetate buffer pH 2.9) at 298 K. 3+ (ClO2 · ) is the time distribution of UV-Vis absorption at 358 nm. (b) is a quadratic plot. Figure 3(a) is the Sc in the presence of styrene (30-90 mM) in a MeCN / H2O (1:1 v / v) solution at 298 K. 3+ (ClO2 · (a) is the time distribution of UV-Vis absorption at 358 nm for the consumption of styrene. (b) is the curve of pseudo-first-order rate constant and styrene concentration. Figure 4 The following are EPR spectra of MeCN solution measured at 298K. (a) is the spectrum of MeCN solution containing NaClO2 (0.10mM) after reflux at 353K for 1 hour. (b) is the spectrum of MeCN solution containing NaClO2 (0.10mM) and CF3COOH (10mM). (c) is the spectrum of MeCN solution containing NaClO2 (0.10mM) and Sc(OTf)3 (10mM). Figure 5 The bond lengths of the DFT-optimized structures are calculated based on the CAM-B3LYP / 6-311+G(d,p) level theoretical calculations. (a) is ClO2 · , (b) is H + ClO2 · , (c) is Sc 3+ ClO2 · . Figure 6 It means that the product is used in an aqueous MeCN solution (MeCN / H2O 1:1 v / v) at room temperature (25°C). 1 HNMR spectrum of the result of following the reaction of styrene (2.0 mM) with NaClO2 (20 mM). Figure 7 The results show that the CD3CN / D2O (4:1 v / v) mixture containing styrene (66 mM) and NaClO2 (200 mM) was heated at 60 °C (333 K) for 0 h and 25 h. 1 HNMR spectrum. * indicates the peak derived from styrene oxide. Figure 8 The results show that the CD3CN / D2O (1:1 v / v) mixture containing styrene (2.0 mM), NaClO2 (20 mM) and Sc(OTf)3 (30 mM) was mixed at 25°C for 0.6 hours and 17 hours. 1 HNMR spectra. * Marks and The markers are peaks derived from 1-phenylethane-1,2-diol and 2-chloro-1-phenylethanol, respectively. Fig. 9The results show that the concentration of styrene (2.0 mM), NaClO2 (20 mM) and CF3COOD (30 mM) in CD3CN / D2O (1:1 v / v) was 0.5 h and 17 h later. 1 HNMR spectra. * Marks and The markers are the peaks derived from 1-phenylethane-1,2-diol and 2-chloro-1-phenylethanol, respectively. Fig.10 is (a)H + ClO2 · and (b) Sc 3+ ClO2 · A diagram of the spin distribution calculated using the CAM-B3LYP / 6-311+G(d,p) level theory. Fig.11 (a) shows the oxygen saturated solution of tetraphenylporphyrin cobalt (II) complex Co(II)TPP ([CoTPP] = 9.0 × 10 -6 M, [O2] = 13 mM) was added with benzethonium chloride (Bzn + ) is a graph showing the time-dependent changes in the ultraviolet + visible light absorption spectrum of the solution obtained. Fig.11 (b) means Fig.11 (a) is a graph showing the temporal change in the increase of the absorption band at 433 nm. Fig.12 is the optimized Bzn by density functional calculation (B3LYP / 6-31G(d) level) + Diagram of the structure. Fig.13 This is the UV+Vis absorption spectrum of NaClO2 (20 mM) collected after mixing with Sc(OTf)3 (40 mM) in aqueous solution at 298 K. Fig.14 The graphs (a) to (c) show the time-dependent changes in the reaction when 10-methyl-9,10-dihydroacridine (AcrH2) (1.4 mM) and sodium chlorite (NaClO2) (2.8 mM) are added to a mixed solution of deoxyacetonitrile / water (1:1 v / v). Fig.15 (a) and (b) are diagrams showing the preparation and Fig.14 The same mixed solution was then added with Bzn + (0.56 mM) with time. Fig.16 (a) and (b) are diagrams showing the preparation and Fig.15 Changes over time of the reaction when Sc(OTf) 3 (3.0 mM) was further added to the same mixed solution. Fig.17 It is a schematic diagram illustrating the presumed reaction mechanism in the oxidation reaction from AcrH2 to 10-methylacridone. Fig.18 (a) is the UV-visible absorption spectrum tracking the oxidation reaction of triphenylphosphine using NaClO2 and scandium trifluoromethanesulfonate. Fig.18 (b) means Fig.18 (a) is a graph showing the relationship between the initial concentration of Ph3P and the concentration of Ph3P=O generated in the reaction. Fig.19 The results show that the mixture of CD3CN / D2O (1:1 v / v) containing styrene (2.0 mM), NaClO2 (6.0 mM) and Sc(OTf)3 (5.6 mM) was heated to 25 °C after 0 hour and 45 hours in an Ar atmosphere. 1 H NMR spectroscopy. Fig. 20 In acetonitrile, in 9- 10-Methylacridine (Acr + -Mes) perchlorate (Acr + -MesClO4 - ) and oxygen to obtain the oxidation reaction product (benzoic acid) obtained by oxidation reaction of the raw material aromatic compound (benzaldehyde) in the presence of 2-nitrogen and oxygen. Fig.21 Benzethonium chloride [Bzn + Cl - ] and a diagram of the Lewis acids of various metal complexes. Fig. 22 In Fig. 22 The ultraviolet-visible absorption spectrum of (a) shows that triphenylphosphine is converted into triphenylphosphine oxide by time-dependent changes. Fig. 22 In Fig. 22 (b) shows the graph of Sc(OTf)3(Sc 3+ ) with time-dependent changes in the concentration of triphenylphosphine (Ph3P) in the presence and absence of ). Fig.23 It is the ESR spectrum graph of the medicine of Example. Fig.24 It is the ESR spectrum graph of the medicine of Example. Fig.25 It is the ESR spectrum graph of the medicine of Example. Fig.26 It is the ESR spectrum graph of the medicine of Example. Fig. 27 This is a graph showing the inhibitory effect of the drug of the example on ulcerative colitis. Fig.28 It is a graph showing changes in intestinal flora using the pharmaceutical agent of the example. DETAILED DESCRIPTION

[0020] Hereinafter, the present invention will be described in further detail with reference to examples, but the present invention is not limited to the following description.

[0021] [1. Free radical generating catalyst] The use of the first to third free radical generating catalysts in the present invention is not particularly limited, and as mentioned above, for example, they can be used in the method for producing the first free radical in the present invention. In addition, the first to third free radical generating catalysts in the present invention can also be used in the method for producing the second to fourth free radicals in the present invention, for example. In addition, in the method for producing the second to fourth free radicals in the present invention, as mentioned above, a Lewis acid with a Lewis acidity of 0.4 eV or more can be used. It can be considered that the Lewis acid with a Lewis acidity of 0.4 eV or more functions as a free radical generating catalyst. Hereinafter, the term "free radical generating catalyst of the present invention" is not limited to the first to third free radical generating catalysts in the present invention, and also includes the Lewis acid with a Lewis acidity of 0.4 eV or more, unless otherwise specified.

[0022] The free radical generating catalyst of the present invention may be, for example, an organic compound or an inorganic substance. The organic substance may be at least one selected from, for example, ammonium, amino acids, peptides, phospholipids, and salts thereof. The inorganic substance may contain one or both of metal ions and non-metal ions. The metal ions may contain one or both of typical metal ions and transition metal ions. The inorganic substance may be, for example, selected from alkaline earth metal ions, rare earth ions, Sc 3+ , Li + , Fe 2+ , Fe 3+ 、Al 3+ , silicate ions and borate ions. Examples of alkaline earth metal ions include ions of calcium, strontium, barium or radium. More specifically, examples include Ca 2+ , Sr 2+ , Ba 2+ and Ra 2+ In addition, "rare earth" is scandium 21 Sc, Yttrium 39 Y and lanthanum 57 La to Lutetium 71 A general term for 17 elements in total of 15 elements of Lu (lanthanide series). Examples of rare earth ions include trivalent cations corresponding to the above 17 elements.

[0023] In addition, the above-mentioned Lewis acid (including counter ions) can be, for example, at least one selected from CaCl2, MgCl2, FeCl2, FeCl3, AlCl3, AlMeCl2, AlMe2Cl, BF3, BPh3, BMe3, TiCl4, SiF4 and SiCl4. Wherein, "Ph" represents phenyl and "Me" represents methyl.

[0024] In addition, among the radical generating catalysts of the present invention, the radical generating catalyst can be appropriately selected according to the purpose in consideration of the strength of reactivity, the strength of acidity, safety, and the like.

[0025] As a result of the research conducted by the present inventors, it was found that ammonium (especially organic ammonium), amino acids, peptides and phospholipids function as free radical generating catalysts. In addition, as a result of further research conducted by the present inventors, it was found that ammonium, amino acids, peptides and phospholipids that function as free radical generating catalysts sometimes have the property of being Lewis acids. That is, the reason why ammonium, amino acids, peptides and phospholipids function as free radical generating catalysts is not yet clear, and it can be inferred that the reason is that the above-mentioned ammonium, amino acids, peptides and phospholipids have the function of being Lewis acids. In addition, as a result of further research conducted by the present inventors, it was found that free radical generating catalysts include organic compounds having at least one of Lewis acidity and Bronsted acidity. It should be noted that in the present invention, "Lewis acid" refers to, for example, a substance that acts as a Lewis acid on the above-mentioned free radical generating source.

[0026] The Lewis acidity of the radical generating catalyst of the present invention is, for example, 0.4 eV or more, 0.5 eV or more, or 0.6 eV or more. The upper limit of the Lewis acidity is not particularly limited, and is, for example, 20 eV or less. In the present invention, as a criterion for determining whether the Lewis acidity is above or below the above value, for example, the value measured by any of the "Lewis acidity measurement method (1)" or "Lewis acidity measurement method (2)" described later is above or below the above value.

[0027] The Lewis acidity can be measured, for example, by the method described in Ohkubo, K.; Fukuzumi, S. Chem. Eur. J., 2000, 6, 4532, J. AM. CHEM. SOC. 2002, 124, 10270-10271 or J. Org. Chem. 2003, 68, 4720-4726. Specifically, it can be measured by the following “Lewis acidity measurement method (1)”.

[0028] (Determination method of Lewis acidity (1)) For a measurement object (e.g., a cation such as a metal) containing tetraphenylporphyrin cobalt, saturated O2, and Lewis acidity in the following chemical reaction formula (1a), wherein M n+ The UV-visible absorption spectrum of acetonitrile (MeCN) was measured at room temperature. The reaction rate constant (k cat ) to calculate the ΔE value (eV) as an indicator of Lewis acidity. cat The larger the value of , the stronger the Lewis acidity. In addition, the Lewis acidity of an organic compound can also be estimated based on the energy level of the lowest unoccupied orbital (LUMO) calculated by quantum chemical calculation. The larger the positive side value, the stronger the Lewis acidity.

[0029]

[0030] It should be noted that an example of the reaction rate constant of CoTPP and oxygen in the presence of a Lewis acid, which is an indicator of Lewis acidity measured (calculated) by the above-mentioned measurement method, is shown below. cat ,M -2 s -1 The numerical value represented by "" is CoTPP and oxygen in the presence of Lewis acid. The numerical value represented by "LUMO, eV" is the energy level of LUMO. In addition, "benzetonium chloride" means benzethonium chloride, "benzalkonium chloride" means benzalkonium chloride, "tetramethylammonium hexafluorophosphate" means tetramethylammonium hexafluorophosphate, "tetrabutylammonium hexafluorophosphate" means tetrabutylammonium hexafluorophosphate, and "ammoniumhexafluorophosphate" means ammonium hexafluorophosphate.

[0031]

Table tpp

[0032] Furthermore, in the present invention, the Lewis acidity may be measured by using ubiquinone 1 (Q1) instead of oxygen molecule (O2) in the Lewis acidity measurement method (1), and by reducing ubiquinone 1 to generate an anion radical of ubiquinone 1. Such a Lewis acidity measurement method may be hereinafter referred to as "Lewis acidity measurement method (2)". In the Lewis acidity measurement method (2), the measurement may be performed in the same manner as in the Lewis acidity measurement method (1), except that ubiquinone 1 (Q1) is used instead of oxygen molecule (O2). Furthermore, in the Lewis acidity measurement method (2), the reaction rate constant (kcat ) to calculate the ΔE value (eV) as an index of Lewis acidity. The Lewis acidity determination method (2) is described in Ohkubo, K.; Fukuzumi, S. Chem. Eur. J., 2000, 6, 4532, for example. The method described in the document can be followed or used as a standard.

[0033] The above-mentioned Lewis acidity determination method (2) can be performed by measuring the reaction rate constant (k cat ) is carried out. Co Tpp: cobalt(II) tetraphenylporphyrin Q1: Ubiquinone 1 In the above chemical formula (1b), M n+ represents the above-mentioned free radical generating catalyst; CoTPP stands for cobalt(II) tetraphenylporphyrin; Q1 represents ubiquinone 1; [(TPP)Co] + represents the tetraphenylporphyrin cobalt(III) cation; (Q1) ·－ Represents the anionic radical of ubiquinone 1.

[0034] The Lewis acidity of the radical generating catalyst of the present invention is, for example, the reaction rate constant (k cat ), that is, the above reaction rate constant (k cat ) measured value (K obs ) can be, for example, 1.0×10 -5 S -1 Above, 2.0×10 -5 S -1 Above, 3.0×10 -5 S -1 Above, 4.0×10 -5 S -1 Above, 5.0×10 -5 S -1 Above, 6.0×10 -5 S -1 Above, 7.0×10 -5 S -1 Above, 8.0×10 -5 S -1 Above, 9.0×10 -5 S -1 Above, 1.0×10 -4 S-1 Above, 2.0×10 -4 S -1 Above, 3.0×10 -4 S -1 Above, 4.0×10 -4 S -1 Above, 5.0×10 -4 S -1 Above, 6.0×10 -4 S -1 Above, 7.0×10 -4 S -1 Above, 8.0×10 -4 S -1 Above, 9.0×10 -4 S -1 Above, 1.0×10 -3 S -1 Above, 2.0×10 -3 S -1 Above, 3.0×10 -3 S -1 Above, 4.0×10 -3 S -1 Above, 5.0×10 -3 S -1 Above, 6.0×10 -3 S -1 Above, 7.0×10 -3 S -1 Above, 8.0×10 -3 S -1 Above, 9.0×10 -3 S -1 Above, 1.0×10 - 2 S -1 Above, 2.0×10 -2 S -1 Above, 3.0×10 -2 S -1 Above, 4.0×10 -2 S -1 Above, 5.0×10 -2 S -1 Above, 6.0×10 -2 S -1 Above, 7.0×10 -2 S -1 Above, 8.0×10 -2 S -1 Above or 9.0×10 -2 S -1 Above, it can also be 1.0×10 -1 S -1Below, 9.0×10 -2 S -1 Below, 8.0×10 -2 S -1 Below, 7.0×10 -2 S -1 Below, 6.0×10 -2 S -1 Below, 5.0×10 - 2 S -1 Below, 4.0×10 -2 S -1 Below, 3.0×10 -2 S -1 Below, 2.0×10 -2 S -1 Below, 1.0×10 -2 S -1 Below, 9.0×10 -3 S -1 Below, 8.0×10 -3 S -1 Below, 7.0×10 -3 S -1 Below, 6.0×10 -3 S -1 Below, 5.0×10 -3 S -1 Below, 4.0×10 -3 S -1 Below, 3.0×10 -3 S -1 Below, 2.0×10 -3 S -1 Below, 1.0×10 -3 S -1 Below, 9.0×10 -4 S -1 Below, 8.0×10 -4 S -1 Below, 7.0×10 -4 S -1 Below, 6.0×10 -4 S -1 Below, 5.0×10 -4 S -1 Below, 4.0×10 -4 S -1 Below, 3.0×10 -4 S -1 Below, 2.0×10 -4 S -1 Below, 1.0×10 -4 S -1 Below, 9.0×10-5 S -1 Below, 8.0×10 -5 S -1 Below or 7.0×10 -5 S -1 the following.

[0035] In the free radical generating catalyst of the present invention, the ammonium may be, for example, a quaternary ammonium, or a tertiary ammonium, a secondary ammonium, a primary ammonium or an ammonium. In addition, the ammonium is not particularly limited, and may be, for example, a nucleic acid base, or an amino acid or a peptide as described below.

[0036] In addition, in the free radical generating catalyst of the present invention, at least one of the above-mentioned compounds selected from ammonium, amino acids, peptides, phospholipids and their salts (the first free radical generating catalyst of the present invention), or a compound having at least one of Lewis acidity and Bronsted acidity (the second free radical generating catalyst of the present invention) can be, for example, a cationic surfactant or a quaternary ammonium type cationic surfactant. Examples of quaternary ammonium cationic surfactants include benzalkonium chloride, benzethonium chloride, cetylpyridinium chloride, cetyltrimethylammonium bromide, dequalinium chloride, edrophonium chloride, didecyldimethylammonium chloride, tetramethylammonium chloride, tetrabutylammonium chloride, benzyltriethylammonium chloride, oxitropium bromide, carbachol, glycopyrronium, safranin, sinapinic acid, tetraethylammonium bromide, cetyltrimethylammonium bromide, succinylcholine, sphingomyelin, ganglioside GM1, denatonium, trigonelline, neostigmine, paraquat, pyridostigmine, phellodendron, pralidoxime iodide, and chloranil. iodide), betaine, betanin, bethanechol, betalain, lecithin, adenine, guanine, cytosine, thymine, uracil and choline (choline chloride such as benzoylcholine chloride and lauroylcholine chloride hydrate, phosphocholine, acetylcholine, choline, dipalmitoylphosphatidylcholine and choline bitartrate, etc.). In the method for producing free radicals of the present invention, the quaternary ammonium is not limited to surfactants.

[0037] In the radical generating catalyst of the present invention, the ammonium may be, for example, ammonium represented by the following chemical formula (XI).

[0038]

[0039] In the above chemical formula (XI), R 11 , R 21 , R 31 and R41 Each is a hydrogen atom or an aromatic ring, or an alkyl group, the alkyl group may contain an ether bond, a carbonyl group, an ester bond or an amide bond, or an aromatic ring, R 11 , R 21 , R 31 and R 41 They can be the same or different. Or, R 11 , R 21 , R 31 , and R 41 Two or more of them can be integrated and bonded to N + Together they form a ring structure, which may be a saturated ring structure or an unsaturated ring structure, may be an aromatic ring or a non-aromatic ring, and may or may not have one or more substituents; X - is an anion; X - For example, these are anions other than peroxodisulfate. R 11 , R 21 , R 31 and R 41 In the above aromatic ring, there is no particular limitation, for example, it may contain heteroatoms or may not contain heteroatoms, and may have substituents or may not have substituents. As the above aromatic ring containing heteroatoms (heteroaromatic ring), for example, nitrogen-containing aromatic rings, sulfur-containing aromatic rings, oxygen-containing aromatic rings, etc. can be cited. As the above aromatic ring without heteroatoms, for example, benzene rings, naphthalene rings, anthracene rings, phenanthrene rings, etc. can be cited. As heteroaromatic rings, for example, pyridine rings, thiophene rings, and pyrene rings can be cited. For example, the nitrogen-containing aromatic ring may not have a positive charge or may have a positive charge. Examples of the nitrogen-containing aromatic ring having no positive charge include a pyrroline ring, a pyridine ring, a pyridazine ring, a pyrimidine ring, a pyrazine ring, a quinoline ring, an isoquinoline ring, an acridine ring, a 3,4-benzoquinoline ring, a 5,6-benzoquinoline ring, a 6,7-benzoquinoline ring, a 7,8-benzoquinoline ring, a 3,4-benzoisoquinoline ring, a 5,6-benzoisoquinoline ring, a 6,7-benzoisoquinoline ring, and a 7,8-benzoisoquinoline ring. Examples of the nitrogen-containing aromatic ring having a positive charge include a pyrroline ring, a pyridine ring, a pyridazine ring, a pyrimidine ring, a pyrazine ring, a quinoline ring, an isoquinoline ring, an acridine ring, a 3,4-benzoquinoline ring, a 5,6-benzoquinoline ring, a 6,7-benzoquinoline ring, and a 7,8-benzoisoquinoline ring. Cyclic, pyridine Cyclic, pyridazine Cyclic, pyrimidine Cyclic, pyrazine Cyclic, quinoline Cyclic, isoquinoline Cyclic, acridine Cyclic, 3,4-benzoquinoline Cyclic, 5,6-benzoquinoline Cyclic, 6,7-benzoquinoline Cyclic, 7,8-benzoquinoline Cyclic, 3,4-Benzisoquinoline Cyclic, 5,6-Benzisoquinoline Cyclic, 6,7-Benzisoquinoline Cyclic, 7,8-Benzisoquinoline Examples of the oxygen-containing aromatic ring or sulfur-containing aromatic ring include aromatic rings obtained by replacing at least one of the carbon atoms or nitrogen atoms of the above-mentioned heteroatom-free aromatic ring or nitrogen-containing aromatic ring with at least one of an oxygen atom and a sulfur atom. In R 11 , R 21 , R 31 and R 41 In the case where the alkyl group or the aromatic ring has a substituent, the substituent is not particularly limited and is arbitrary, and examples thereof include a sulfo group, a nitro group, and a diazo group.

[0040] The ammonium represented by the above chemical formula (XI) may be, for example, ammonium represented by the following chemical formula (XII).

[0041]

[0042] In the above chemical formula (XII), R 111 is an alkyl group having 5 to 40 carbon atoms, which may contain an ether bond, a keto (carbonyl) group, an ester bond or an amide bond, a substituent group, or an aromatic ring; R 21 and X - The same as the above chemical formula (XI). R 111 In the above, the aromatic ring is not particularly limited, and may or may not contain a heteroatom, and may or may not have a substituent. 111 The specific examples of the aromatic ring are not particularly limited, for example, 11 , R 21 , R 31 and R 41 same. R 111 In the case where the alkyl group or the aromatic ring has a substituent, the substituent is not particularly limited and is arbitrary, for example, 11 , R 21 , R 31 and R 41 same.

[0043] In the above chemical formula (XII), R 21For example, it may be a methyl group or a benzyl group, and one or more hydrogen atoms of the benzyl ring of the benzyl group may be substituted by any substituent or may not be substituted, and the arbitrary substituent may be, for example, an alkyl group, an unsaturated aliphatic hydrocarbon group, an aryl group, a heteroaryl group, a halogen group, a hydroxyl group (-OH), a mercapto group (-SH) or an alkylthio group (-SR, R is an alkyl group).

[0044] The ammonium salt represented by the above chemical formula (XII) may be, for example, ammonium represented by the following chemical formula (XIII).

[0045]

[0046] In the above chemical formula (XIII), R 111 and X - Same as the above chemical formula (XII).

[0047] The ammonium represented by the above chemical formula (XI) may be, for example, an ammonium salt represented by the following chemical formula (XIV).

[0048] In the above chemical formula (XIV), R 100 A cyclic structure may be formed, and the cyclic structure may be a saturated cyclic structure or an unsaturated cyclic structure, may be an aromatic ring or a non-aromatic ring, and may have one or more substituents or may not have one or more substituents; R 11 and X - The same as the above chemical formula (XI).

[0049] The ammonium salt represented by the above chemical formula (XI) may be, for example, an ammonium salt represented by the following chemical formula (XV).

[0050]

[0051] In the above chemical formula (XV), Each Z is CH or N, and may be the same or different. In the case of CH, H may be substituted by a substituent; R 11 and X - The same as the above chemical formula (XI).

[0052] The ammonium salt represented by the above chemical formula (XI) may be, for example, an ammonium salt represented by the following chemical formula (XVI).

[0053]

[0054] In the above chemical formula (XVI), R 101, R 102 , R 103 and R 104 are each a hydrogen atom or a substituent, R 101 , R 102 , R 103 and R 104 They can be the same or different. Or, R 101 , R 102 , R 103 and R 104 Two or more of them can be integrated and bonded to N + Together they form a ring structure, which may be a saturated ring structure or an unsaturated ring structure, may be an aromatic ring or a non-aromatic ring, and may or may not have one or more substituents; Z is CH or N. In the case of CH, H may be substituted by a substituent; R 11 and X - The same as the above chemical formula (XI).

[0055] The ammonium salt represented by the above chemical formula (XI) may be, for example, an ammonium salt represented by the following chemical formula (XVII).

[0056]

[0057] In the above chemical formula (XVII), R 111 ~R 118 are each a hydrogen atom or a substituent, R 111 ~R 118 They can be the same or different. Or, R 111 ~R 118 Two or more of them may be integrated to form a cyclic structure, and the cyclic structure may be an aromatic ring or a non-aromatic ring, and may or may not have one or more substituents; Z is CH or N. In the case of CH, H may be substituted by a substituent; R 11 and X - The same as the above chemical formula (XI).

[0058] The ammonium salt represented by the above chemical formula (XI) can be, for example, at least one selected from benzethonium chloride, benzalkonium chloride, cetyltrimethylammonium chloride, tetramethylammonium chloride, ammonium chloride, methylammonium chloride and tetrabutylammonium chloride. In addition, the ammonium salt represented by the above chemical formula (XII) is particularly preferably benzethonium chloride.

[0059] It should be noted that benzethonium chloride (Bzn + Cl - ) can be represented by the following chemical formula, for example. In addition, benzalkonium chloride can be represented by the above chemical formula (XIII), R 111 is an alkyl group having 8 to 18 carbon atoms, X - A compound of chloride ion.

[0060] In the above chemical formulas (XI), (XII), (XIII), (XIV), (XV), (XVI) and (XVII), X - is any anion and is not particularly limited. - It is not limited to monovalent anions, and may be divalent, trivalent, or any other anion. When the anion has a multivalent charge such as divalent or trivalent, for example, the number of molecules of ammonium (univalent) in the above chemical formulas (XI), (XII), (XIII), (XIV), (XV), (XVI), and (XVII) is the number of molecules of the anion × the number of valence of the anion (for example, when the anion is divalent, the number of molecules of ammonium (univalent) is twice the number of molecules of the anion). - Examples of the ion include halogen ions (fluoride ion, chloride ion, bromide ion, iodide ion), acetate ion, nitrate ion, sulfate ion and the like.

[0061] In the present invention, the free radical generating catalyst is, for example, the above chemical formula (XI), (XII), (XIII), (XIV), (XV), (XVI) and (XVII), but is not limited thereto, and may be ammonium of any structure containing an aromatic ring. The above aromatic ring is not particularly limited, and examples thereof include R 11 , R 21 , R 31 and R 41 The aromatic ring exemplified in .

[0062] In the present invention, the radical generating catalyst may be, for example, a sulfonic acid amine or its ammonium. The sulfonic acid amine refers to, for example, an amine having a sulfonic group (sulfonic acid group) in the molecule. Examples of the sulfonic acid amines include taurine, aminosulfonic acid, 3-amino-4-hydroxy-1-naphthalenesulfonic acid, aminosulfonic acid, p-toluidine-2-sulfonic acid, o-anisidine-5-sulfonic acid, direct blue 14, 3-[N,N-bis(2-hydroxyethyl)amino]-2-hydroxypropanesulfonic acid, 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate, aminomethanesulfonic acid, 3-sulfopropylamine, 2-aminobenzenesulfonic acid, R(+)-3-aminotetrahydrofurantoluene, 4-amino-5-hydroxy-1,7-naphthalene disulfonic acid, N-(2-acetamido)-2-aminoethanesulfonic acid, sodium 4'-amino-3'-methoxyazobenzene-3-sulfonate, lapatinib ditoluenesulfonate, and the like. ditosylate), N-tris(hydroxymethyl)methyl-2-aminoethanesulfonic acid, 8-amino-1,3,6-naphthalenetrisulfonic acid disodium hydrate, 1-aminonaphthalene-2-sulfonic acid, (2S,3S)-3-amino-2-methyl-4-oxo-1-oxetanesulfonic acid, sodium 3-(1-naphthylamino)propanesulfonate, 3-methyl-4-aminobenzenesulfonic acid, sodium 3-cyclohexylamino-2-hydroxypropanesulfonate, N-tris(hydroxymethyl)methyl-2-aminoethanesulfonic acid Sodium, 4-amino-1-naphthalenesulfonic acid, sodium aminosulfonate, tricaine, sodium p-aminobenzenesulfonate, 1,4-phenylenediamine-2-sulfonic acid, p-methoxyaniline-2-sulfonic acid, 6-amino-1-naphthalenesulfonic acid, 3,4-diaminobenzenesulfonic acid, 3-amino-4-chlorobenzenesulfonic acid, 3-[(4-amino-3-methylphenyl)azo]benzenesulfonic acid, 3-amino-4-hydroxy-5-nitrobenzenesulfonic acid, 5-amino-6-hydroxy-3-nitrobenzenesulfonic acid, 4-acetamido-2-aminobenzenesulfonic acid hydrate sulfonic acid, 2-aminophenol-4-sulfonic acid, 1-amino-2-methoxy-5-methyl-4-benzenesulfonic acid, dansyl acid, aminosulfonic acid [(1S,2S,4R)-4-[4-[[(1S)-2,3-dihydro-1H-inden-1-yl]amino]-7H-pyrrolo[2,3-d]pyrimidin-7-yl]-2-hydroxycyclopentyl]methyl ester, 5-sulfo-4'-diethylamino-2,2'-dihydroxyazobenzene, 2-aminonaphthalene-6,8-disulfonic acid, 2-[ Sodium N,N-bis(2-hydroxyethyl)amino]-1-ethanesulfonate, 3-acetyl-2-(methylaminosulfonyl)thiophene, sodium 4-amino-2-chlorotoluene-5-sulfonate, 5-(3-amino-5-oxo-2-pyrazolin-1-yl)-2-phenoxybenzenesulfonic acid, potassium aminosulfonate, p-aminoazobenzenesulfonic acid, 3-[(3-cholamidopropyl)dimethylammonio]-2-hydroxy-1-propanesulfonate, sodium 3-amino-2,7-naphthalene disulfonate, 3-[N,N-bis(hydroxyethyl)amino]-2-hydroxypropanesulfonic acid sodium salt, bis(amidosulfate) cobalt(II), 3-(4-amino-3-methoxyphenylazo)benzenesulfonic acid, nickel(II) sulfamate tetrahydrate, sodium 2,4-diaminobenzenesulfonate, 5-amino-2-chlorotoluene-4-sulfonic acid, 2,5-dichloro-p-aminobenzenesulfonic acid, 4-methylbenzenesulfonic acid, APTS (aminopyrene trisulfonic acid), 4'-aminoazobenzene-3-sulfonic acid, Pontacyl Carmine 2B 2B), p-anisidine-3-sulfonic acid, 4,4'-bis(4-amino-1-naphthylazo)-2,2'-stilbenesulfonic acid, 3-aminonaphthalene-8-hydroxy-4,6-disulfonic acid, sodium 4-amino-1,5-naphthalene disulfonate, sodium 4-aminoazobenzene-4'-sulfonate, 5-amino-2-methylbenzenesulfonic acid, disodium 7-amino-1,3-naphthalene disulfonate, monosodium 4,8-diamino-9,10-dihydro-1,5-dihydroxy-9,10-dioxo-2-anthracenesulfonic acid (ALIZARIN SAFIROL SE), sodium 7-amino-2-naphthalenesulfonate, 6-amino-5-bromopyridine-3-sulfonic acid, 2-aminoethanethiol p-toluenesulfonate, sodium 2-amino-1-naphthalenesulfonate, disodium 6-amino-1,3-naphthalene disulfonate hydrate, N,N,N',N'-tetraethylsulfamide, 5-amino-2-ethoxybenzenesulfonic acid, 3,5-diamino-2,4,6-trimethylbenzenesulfonic acid, 7-amino-1-naphthalenesulfonic acid, Guanidine sulfamate, 2-amino-5-nitrobenzenesulfonic acid, nickel(II) diamide sulfate, disodium 4-amino-4'-nitrostilbene-2,2'-disulfonate, monosodium aniline-2,5-disulfonate, 5-amino-1-naphthol-3-sulfonic acid hydrate, sodium 2,5-dichloro-p-aminobenzenesulfonate, 6-aminohexanoic acid hexyl p-toluenesulfonate, racemic-(R*)-2-(4-chlorophenyl)-3-amino-1-propanesulfonic acid Acid, 2-(N,N-dipropyl)aminoanisole-4-sulfonic acid, 2-amino-4-chlorophenol-6-sulfonic acid, 6-amino-1,3-naphthalene disulfonic acid, 5,10,15,20-tetrakis[4-(trimethylammonium)phenyl]-21H,-23H-porphyrin tetra-p-toluenesulfonate, 5-amino-2-[(4-aminophenyl)amino]benzenesulfonic acid, 4-amino-3-chlorobenzenesulfonic acid, 2-aminobenzenesulfonic acid Phenyl ester, 4-acetylamino-4'-isothiocyanatostilbene-2,2'-disulfonic acid disodium, (S)-3-amino-2-oxetanone p-toluenesulfonate, 5-acetylamino-4-hydroxy-2,7-naphthalene disulfonic acid disodium, 2-phenylamino-5-aminobenzenesulfonic acid, 4-octadecylamino-4-oxo-2-[(sodium oxy)sulfonyl]butane sodium, 3,5-diamino-4-methylbenzenesulfonic acid, etc.

[0063] In the present invention, the free radical generating catalyst may be, for example, a nicotinic amine or its ammonium. The nicotinic amine, for example, refers to an amine having a cyclic structure in the molecule, and the cyclic structure includes a nicotine skeleton. Examples of the nicotinic amine include nicotinamide, alkaloids, and the like.

[0064] In the present invention, the free radical generating catalyst may be, for example, a nitrite-type amine or a nitrite-type ammonium. The nitrite-type amine or the nitrite-type ammonium refers to, for example, a compound obtained by reacting an amine with nitrous acid or a nitrous acid derivative. Examples of the nitrite-type amine or the nitrite-type ammonium include diazo compounds, diazo compounds, Salts, N-nitroso compounds, C-nitroso compounds, etc.

[0065] In the present invention, the above-mentioned ammonium may contain a plurality of ammonium structures (N + ). Furthermore, the above-mentioned ammonium can aggregate multiple molecules through π electron interaction to form dimers or trimers.

[0066] In the present invention, the above-mentioned amino acids are not particularly limited. For example, the above-mentioned amino acids each contain at least one amino group or imino group and a carboxyl group in the molecule. The above-mentioned amino acids may be, for example, α-amino acids, β-amino acids, γ-amino acids, or amino acids other than the above-mentioned amino acids. The above-mentioned amino acids may be, for example, amino acids constituting proteins, and specifically, for example, may be at least one selected from glycine, alanine, valine, leucine, isoleucine, serine, threonine, aspartic acid, glutamic acid, asparagine, glutamine, lysine, hydroxylysine, arginine, cysteine, cystine, methionine, phenylalanine, tyrosine, tryptophan, histidine, proline, and 4-hydroxyproline.

[0067] In the present invention, the peptide is not particularly limited. The peptide may be, for example, a substance obtained by bonding two or more amino acid molecules through a peptide bond. The peptide may be, for example, at least one of oxidized glutathione (GSSG) and reduced glutathione (GSH).

[0068] In the present invention, the above-mentioned phospholipid is not particularly limited. The above-mentioned phospholipid, for example, can be a lipid containing a phosphorus atom in the molecule, for example, a lipid containing a phosphate bond (POC) in the molecule. The above-mentioned phospholipid, for example, can have at least one of an amino group, an imino group, an ammonium group and an iminium group in the molecule, or can have no such groups. The above-mentioned phospholipid, for example, can be at least one selected from phosphatidylserine, phosphatidylcholine, phosphatidic acid, phosphatidylethanolamine, phosphatidylglycerol and cardiolipin.

[0069] The free radical generator of the present invention may include, for example, a Bronsted acid. The acid dissociation constant pK of the Bronsted acid isa For example, it is 5 or more. a The upper limit of is not particularly limited, and is, for example, 50 or less.

[0070] The free radical generating catalyst of the present invention can catalyze the generation of free radicals from a free radical generating source in vitro, for example, or in vivo. The in vivo may be, for example, the human body, or may be the body of an animal other than a human.

[0071] The free radical generating catalyst of the present invention can, for example, catalyze the generation of free radicals from a free radical generating source in a digestive organ. The above-mentioned digestive organ can, for example, be at least one selected from the oral cavity, pharynx, esophagus, stomach, duodenum, small intestine and large intestine. The above-mentioned digestive organ can, for example, be a large intestine. The above-mentioned small intestine can, for example, be at least one selected from the duodenum, jejunum and ileum. The above-mentioned large intestine can, for example, be at least one selected from the cecum, colon and rectum. The free radical generating catalyst of the present invention can, for example, be used for sterilization in the above-mentioned digestive organs, induction of changes in intestinal flora, treatment of ulcerative colitis or suppression of symptoms, etc.

[0072] [2. Method for producing free radicals] Next, the method for producing radicals of the present invention will be described.

[0073] The method for producing free radicals in the present invention is as described above, including a mixing step of mixing the free radical generating catalyst and the free radical generating source of the present invention. The mixture obtained by the above-mentioned mixing step may further contain any substance other than the free radical generating catalyst and the free radical generating source of the present invention, or may not contain the above-mentioned substance. For example, in the above-mentioned mixing step, it is preferred to further mix the solvent from the viewpoint of reactivity, etc. It should be noted that in the present invention, the "solvent" may dissolve the above-mentioned free radical generating catalyst, the free radical generating source, etc., or may not dissolve the above-mentioned substance. For example, after the above-mentioned mixing step, the free radical generating catalyst and the free radical generating source of the present invention may each be in a state of being dissolved in the above-mentioned solvent, or may be in a state of being dispersed or precipitated in the above-mentioned solvent.

[0074] The method for producing free radicals of the present invention includes, for example, a free radical production step of producing free radicals by reacting in the obtained mixture after the above-mentioned mixing step. The above-mentioned mixture, as described above, may be, for example, a solution state, a suspension state, a colloidal state, etc. From the viewpoint of reactivity, the above-mentioned mixture is preferably, for example, a solution state or a colloidal state. In the above-mentioned free radical production step, for example, the above-mentioned mixture may be left alone at room temperature, or the above-mentioned mixture may be heated, irradiated with light, etc. as required. The reaction temperature and reaction time in the above-mentioned free radical production step are not particularly limited, and for example, they may be appropriately set according to the types of reactants (raw materials) and target products, etc. In the case of light irradiation, the wavelength of the irradiation light is not particularly limited, and for example, it may be appropriately set according to the absorption band of the reactants (raw materials), etc. It should be noted that the reaction time and reaction temperature may also be adjusted, for example, by the concentration of the free radical generating catalyst and the free radical generating source of the above-mentioned present invention in the above-mentioned mixture. For example, by increasing the above-mentioned concentration, the reaction time can be shortened, but the present invention is not limited by this description.

[0075] The concentration of the free radical generating catalyst of the present invention is not particularly limited. For the solvent, for example, the reaction mol·L is not particularly limited, and can be appropriately set according to the types of reactants (raw materials) and target products. In addition, the solvent is not particularly limited, and can be water or an organic solvent. As an organic solvent, for example, halogenated solvents such as dichloromethane, chloroform, and carbon tetrachloride, ketones such as acetone, nitrile solvents such as acetonitrile, alcohol solvents such as methanol and ethanol, acetic acid solvents, sulfuric acid solvents, etc. can be cited. These solvents can be used alone or in combination of two or more. The acetic acid solvent and sulfuric acid solvent can, for example, dissolve acetic acid or sulfuric acid in water, and they function as Lewis acids or Bronsted acids while serving as solvents. The type of the solvent can be distinguished and used according to the solubility of the solute (for example, the free radical generating catalyst of the present invention, the free radical generating source, etc.).

[0076] As mentioned above, the method for producing free radicals of the present invention can be reacted by heating, but it is also possible to react and produce free radicals by only irradiating with light without heating or only standing at room temperature without heating or irradiating with light. It should be noted that the definition of "room temperature" is not particularly limited, for example, 5 to 35 ° C. Since heating is not required, the cost of heating by, for example, an electric furnace is not required, and the manufacturing cost of free radicals can be greatly reduced. In addition, since heating is not required, the unpredictable runaway reaction and the accumulation of peroxides caused by, for example, free radical chains can be suppressed, so the safety of the reaction is significantly improved, and the cost can be further reduced. Wherein, these descriptions are illustrative and there is no limitation on the present invention.

[0077] The method for producing free radicals of the present invention may further include, for example, a light irradiation step of irradiating the mixture obtained by the above-mentioned mixing step. And, as mentioned above, the free radicals can be produced by the reaction caused by the above-mentioned light irradiation. With respect to the wavelength of the irradiation light, for example, as mentioned above. The light source is not particularly limited, for example, if the visible light contained in natural light such as sunlight, it can be easily excited. In addition, for example, instead of the above-mentioned natural light, or on this basis, a light source such as a xenon lamp, a halogen lamp, a fluorescent lamp, a mercury lamp, etc. may be appropriately used, or the above-mentioned light source may not be used. In addition, a filter that removes (cuts) wavelengths other than the necessary wavelength may be appropriately used, or the above-mentioned filter may not be used.

[0078] In the method for producing free radicals of the present invention, the free radical generating source may include at least one selected from halogen ions, hypohalite ions, halogen ions, and perhalate ions. The free radical generating source may include chlorite ions, for example. The free radical generating source may include oxyacids or salts thereof (for example, halogen oxyacids or salts thereof). As the oxyacids, for example, boric acid, carbonic acid, orthocarbonic acid, carboxylic acid, silicic acid, nitrous acid, nitric acid, phosphorous acid, phosphoric acid, arsenic acid, sulfurous acid, sulfuric acid, sulfonic acid, sulfinic acid, chromic acid, dichromic acid, and permanganic acid may be cited. Halogen oxyacids may include chlorine oxyacids such as hypochlorous acid, chlorous acid, chloric acid, and perchloric acid; bromine oxyacids such as hypobromous acid, bromous acid, bromic acid, and perbromic acid; and iodine oxyacids such as hypoiodous acid, iodous acid, iodic acid, and periodic acid.

[0079] The free radical generating source can be appropriately selected according to the application, for example, by considering the reactivity strength of the free radical species, etc. For example, hypochlorous acid, which has a strong reactivity, and chlorous acid, which has a slightly more stable reactivity than hypochlorous acid and is easier to control in reaction, can be used according to the purpose.

[0080] In the method for producing free radicals of the present invention, the free radical generating source may include, for example, an electron donor·acceptor linked molecule. The electron donor·acceptor linked molecule is not particularly limited, for example, the electron donor site may be one or more electron donating groups, and the electron acceptor site may be one or more aromatic cations. In this case, the aromatic cation may be a monocyclic ring or a condensed ring, the aromatic ring may contain heteroatoms or may not contain heteroatoms, and may or may not have substituents other than the electron donating groups. In addition, the number of ring constituent atoms of the aromatic ring forming the aromatic cation is not particularly limited, for example, it is a 5- to 26-membered ring.

[0081] The aromatic ring forming the aromatic cation is preferably selected from pyrroline Cyclic, pyridine Cyclic, quinoline Cyclic, isoquinoline Cyclic, acridine Cyclic, 3,4-benzoquinoline Cyclic, 5,6-benzoquinoline Cyclic, 6,7-benzoquinoline Cyclic, 7,8-benzoquinoline Cyclic, 3,4-Benzisoquinoline Cyclic, 5,6-Benzisoquinoline Cyclic, 6,7-Benzisoquinoline Cyclic, 7,8-Benzisoquinoline At least one of the rings obtained by replacing at least one of the carbon atoms constituting the rings with a heteroatom. For example, if acridine Cyclic, benzoquinoline Benzisoquinoline Aromatic cations having a macrocyclic shape (having a large number of π electrons) such as a ring, for example, have an absorption band shifted to the long wavelength side and can also be excited by visible light by having absorption in the visible light region.

[0082] The electron-donating group is preferably at least one selected from a hydrogen atom, an alkyl group and an aromatic ring. In this case, the aromatic ring may further have one or more substituents on the ring, and the substituents may be the same or different in the case of multiple substituents, and the electron-donating group may be the same or different in the case of multiple substituents. In addition, in the electron-donating group in this case, the alkyl group is more preferably a straight-chain or branched alkyl group having 1 to 6 carbon atoms. In addition, in the electron-donating group, the aromatic ring is more preferably at least one selected from a benzene ring, a naphthalene ring, an anthracene ring, a phenanthrene ring, a pyridine ring, a thiophene ring and a pyrene ring. In the electron-donating group, the substituent on the aromatic ring is more preferably at least one selected from an alkyl group, an alkoxy group, a primary amine to a tertiary amine, a carboxylic acid and a carboxylic acid ester. In Ar, the substituent on the aromatic ring is further preferably at least one selected from a straight-chain or branched alkyl group having 1 to 6 carbon atoms, a straight-chain or branched alkoxy group having 1 to 6 carbon atoms, a primary amine to a tertiary amine, a carboxylic acid and a carboxylic acid ester. It should be noted that, among the substituents on the aromatic ring, "carboxylic acid" refers to a carboxyl group or a group having a carboxyl group added to the terminal (e.g., carboxyalkyl, etc.), and "carboxylate" refers to a carboxylate group and an acyloxy group such as an alkoxycarbonyl group and a phenoxycarbonyl group. As the alkyl group in the carboxyalkyl group, for example, a linear or branched alkyl group having 1 to 6 carbon atoms is preferred, and as the alkoxy group in the alkoxycarbonyl group, for example, a linear or branched alkoxy group having 1 to 6 carbon atoms is preferred.

[0083] The electron donating group is further preferably selected from phenyl, o-tolyl, m-tolyl, p-tolyl, 2,3-dimethylphenyl, 2,4-dimethylphenyl, 2,5-dimethylphenyl, 2,6-dimethylphenyl, 3,4-dimethylphenyl, 3,5-dimethylphenyl, 2,3,4-trimethylphenyl, 2,3,5-trimethylphenyl, 2,3,6-trimethylphenyl, At least one of trimethylphenyl (2,4,6-trimethylphenyl) and trimethylphenyl (3,4,5-trimethylphenyl). Among these, from the viewpoint of the life of the electron transfer state (charge separation state), it is particularly preferred It should be noted that The reason why particularly excellent effects are obtained by adding two methyl groups is not clear, but it is considered that, for example, two methyl groups are present at the ortho position. The benzene ring of the base is easily orthogonal to the aromatic ring of the above aromatic cation. There is less hyperconjugation inside the base, etc. However, this is just one example of a mechanism that can be presumed, and the present invention is not limited in any way.

[0084] The electron donor-acceptor linked molecule is preferably a nitrogen-containing aromatic cation derivative represented by any one of the following formulas (A-1) to (A-8), a quinoline represented by the following formula (I), etc., from the viewpoints of the life span of the electron transfer state (charge separation state), the oxidizing ability, the reducing ability, etc. ionic derivatives, their stereoisomers and tautomers, and at least one of their salts.

[0085]

[0086]

[0087] In the above formulas (A-1) to (A-8), R is a hydrogen atom or any substituent; Ar is the above electron donating group, which may be one or more, and in the case of multiple electron donating groups, they may be the same or different; The nitrogen-containing aromatic ring forming the nitrogen-containing aromatic cation may have one or more arbitrary substituents other than R and Ar, or may not have one or more arbitrary substituents other than R and Ar; In the above formula (I), R 1 is a hydrogen atom or any substituent; Ar 1 ~Ar 3 Each is a hydrogen atom or the above electron-donating group, which may be the same or different. Ar 1 ~Ar 3 At least one of the above-mentioned electron-donating groups is an electron-donating group.

[0088] In the above formulas (A-1) to (A-8), R is preferably a hydrogen atom, an alkyl group, a benzyl group, a carboxyalkyl group (an alkyl group having a carboxyl group added to the terminal), an aminoalkyl group (an alkyl group having an amino group added to the terminal), or a polyether chain. R is more preferably a hydrogen atom, a straight or branched alkyl group having 1 to 6 carbon atoms, a benzyl group, a straight or branched alkyl group having 1 to 6 carbon atoms having a carboxyl group added to the terminal, a straight or branched alkyl group having 1 to 6 carbon atoms having an amino group added to the terminal, or a polyethylene glycol (PEG) chain. The PEG chain is an example of the above polyether chain, but the type of the above polyether chain is not limited thereto, and may be any polyether chain. In R, the degree of polymerization of the above polyether chain is not particularly limited, and is, for example, 1 to 100, preferably 1 to 50, and more preferably 1 to 10. When the above polyether chain is a PEG chain, the degree of polymerization is not particularly limited, and is, for example, 1 to 100, preferably 1 to 50, and more preferably 1 to 10.

[0089] The electron donor-acceptor linked molecule is more preferably selected from 9-substituted acridines represented by the following formula (A-9): ions, and at least one of their tautomers and stereoisomers.

[0090]

[0091] In the above formula (A-9), R and Ar are the same as in the above formula (A-1).

[0092] In addition, the electron donor-acceptor linked molecule is particularly preferably a 9- 10-Methylacridine ions. The 9- 10-Methylacridine Ions can generate a long-life electron transfer state (charge separation state) having high oxidizing power and high reducing power by photoexcitation. As the excitation light for the photoexcitation, for example, visible light can be used.

[0093]

[0094] In addition, as the 9-substituted acridine represented by the above formula (A-9) Examples of the ions include the following (A-101) to (A-116) in addition to the above-mentioned (A-10).

[0095]

Table A1

[0096] In addition, the quinoline represented by the above formula (I) In ionic derivatives, R 1For example, a hydrogen atom, an alkyl group, a benzyl group, a carboxyalkyl group (an alkyl group having a carboxyl group added to the terminal), an aminoalkyl group (an alkyl group having an amino group added to the terminal), or a polyether chain is preferred. 1 More preferably, it is, for example, a hydrogen atom, a linear or branched alkyl group having 1 to 6 carbon atoms, a benzyl group, a linear or branched alkyl group having 1 to 6 carbon atoms with a carboxyl group added to the terminal, a linear or branched alkyl group having 1 to 6 carbon atoms with an amino group added to the terminal, or a polyethylene glycol (PEG) chain. The PEG chain is an example of the above-mentioned polyether chain, but the type of the above-mentioned polyether chain is not limited thereto, and any polyether chain may be used. 1 In the embodiment, the degree of polymerization of the polyether chain is not particularly limited, and is, for example, 1 to 100, preferably 1 to 50, and more preferably 1 to 10. When the polyether chain is a PEG chain, the degree of polymerization is not particularly limited, and is, for example, 1 to 100, preferably 1 to 50, and more preferably 1 to 10. 1 ~Ar 3 For example, each is preferably a hydrogen atom, an alkyl group or an aromatic ring, and the alkyl group is more preferably a linear or branched alkyl group having 1 to 6 carbon atoms. 1 ~Ar 3 In the above-mentioned aromatic ring, one or more substituents may be further present on the ring. In the case of a plurality of substituents, the substituents may be the same or different.

[0097] In the above formula (I), Ar 1 ~Ar 3 In the above-mentioned aromatic ring, for example, it is more preferable that the aromatic ring is a benzene ring, a naphthalene ring, an anthracene ring, a phenanthrene ring, a pyridine ring, a thiophene ring or a pyrene ring. 1 ~Ar 3 In the above, the substituent on the aromatic ring is more preferably an alkyl group, an alkoxy group, a primary amine to a tertiary amine, a carboxylic acid or a carboxylic acid ester, and is further preferably a linear or branched alkyl group having 1 to 6 carbon atoms, a linear or branched alkoxy group having 1 to 6 carbon atoms, a primary amine to a tertiary amine, a carboxylic acid or a carboxylic acid ester. The above secondary amine is not particularly limited, and is preferably an alkylamino group, and is more preferably a linear or branched alkylamino group having 1 to 6 carbon atoms. The above tertiary amine is not particularly limited, and is preferably a dialkylamino group, and is more preferably a dialkylamino group having a linear or branched alkyl group having 1 to 6 carbon atoms.

[0098] It should be noted that Ar 1 ~Ar 3 In the substituents on the aromatic rings, "carboxylic acid" refers to a carboxyl group or a group with a carboxyl group added to the terminal (e.g., carboxyalkyl, etc.), and "carboxylate" refers to carboxylate groups such as alkoxycarbonyl and phenoxycarbonyl, and acyloxy groups. The alkyl group in the carboxyalkyl group is preferably, for example, a straight-chain or branched-chain alkyl group having 1 to 6 carbon atoms, and the alkoxy group in the alkoxycarbonyl group is preferably, for example, a straight-chain or branched-chain alkoxy group having 1 to 6 carbon atoms.

[0099] The quinoline represented by the above formula (I) Among the ionic derivatives, from the viewpoints of long life of the charge separation state, high oxidizing power, high reducing power, etc., for example, quinoline represented by any one of the following formulae 1 to 5 is particularly preferred. Ionic derivatives.

[0100]

[0101] In addition to the above compounds 1 to 5, for example, compounds 6 to 36 shown in Tables 2 and 3 below are particularly preferred. In Tables 2 and 3 below, the structures of compounds 6 to 36 are represented by R in the above formula (I): 1 and Ar 1 ~Ar 3 In addition, by referring to the Examples described below, those skilled in the art can easily produce and use Compounds 6 to 36 according to Compounds 1 to 5 without conducting repeated experiments or highly complicated experiments.

[0102]

Table A2

[0103]

Table A3

[0104] The electron donor-acceptor linked molecule can use a commercial product or can be appropriately manufactured (synthesized). In the case of manufacturing, the manufacturing method is not particularly limited, for example, it can be appropriately manufactured by a known manufacturing method or with reference to a known manufacturing method. Specifically, for example, the manufacturing method described in Japanese Patent Gazette No. 5213142 can be used.

[0105] In addition, in the present invention, when there are isomers such as tautomers or stereoisomers (for example, geometric isomers, conformational isomers and optical isomers) in a compound (for example, the above-mentioned ammonium, the above-mentioned amino acid, the above-mentioned peptide, the above-mentioned phospholipid, the above-mentioned electron donor·acceptor linked molecule, etc.), all isomers can be used in the present invention unless otherwise specified. In addition, when a compound (for example, the above-mentioned electron donor·acceptor linked molecule, etc.) can form a salt, the above-mentioned salt can also be used in the present invention unless otherwise specified. The above-mentioned salt may be an acid addition salt or a base addition salt. In addition, the acid forming the above-mentioned acid addition salt may be an inorganic acid or an organic acid, and the base forming the above-mentioned base addition salt may be an inorganic base or an organic base. As the above-mentioned inorganic acid, there is no particular limitation, for example, sulfuric acid, phosphoric acid, hydrofluoric acid, hydrochloric acid, hydrobromic acid, hydroiodic acid, hypofluoric acid, hypochlorous acid, hypobromous acid, hypoiodous acid, fluorous acid, chlorous acid, bromic acid, iodous acid, fluoric acid, chloric acid, bromic acid, iodic acid, perfluoric acid, perchloric acid, perbromic acid and periodic acid can be cited. The above-mentioned organic acid is also not particularly limited, for example, p-toluenesulfonic acid, methanesulfonic acid, oxalic acid, p-bromobenzenesulfonic acid, carbonic acid, succinic acid, citric acid, benzoic acid and acetic acid can be cited. As the above-mentioned inorganic base, there is no particular limitation, for example, ammonium hydroxide, alkali metal hydroxide, alkaline earth metal hydroxide, carbonate and bicarbonate can be cited, more specifically, for example, sodium hydroxide, potassium hydroxide, potassium carbonate, sodium carbonate, sodium bicarbonate, potassium bicarbonate, calcium hydroxide and calcium carbonate can be cited. The above-mentioned organic base is also not particularly limited, for example, ethanolamine, triethylamine and tris (hydroxymethyl) aminomethane can be cited. The method for producing these salts is not particularly limited, and they can be produced, for example, by appropriately adding the above-mentioned acid or base to the above-mentioned compound by a known method.

[0106] In addition, in the present invention, chain substituents (such as alkyl groups, unsaturated aliphatic hydrocarbon groups, etc.) may be straight-chain or branched unless otherwise specified, and the number of carbon atoms is not particularly limited, for example, 1 to 40, 1 to 32, 1 to 24, 1 to 18, 1 to 12, 1 to 6 or 1 to 2 (2 or more in the case of unsaturated hydrocarbon groups). In addition, in the present invention, the number of ring members (the number of atoms constituting the ring) of cyclic groups (such as aryl groups, heteroaryl groups, etc.) is not particularly limited, and may be, for example, 5 to 32, 5 to 24, 6 to 18, 6 to 12 or 6 to 10. In addition, in the case where isomers exist in the substituents, any isomer may be used unless otherwise specified, for example, in the case of abbreviated "naphthyl", it may be 1-naphthyl or 2-naphthyl.

[0107] [3. Method for producing oxidation reaction product] The method for producing the oxidation reaction product of the present invention is as described above. The invention relates to a method for producing an oxidation reaction product by oxidizing an oxide, characterized in that it comprises: a free radical production step of producing the free radical by the free radical production method of the present invention; and An oxidation reaction step of causing the oxidized substance to react with an oxidant by the action of the free radicals to generate the oxidation reaction product.

[0108] The method for producing the oxidation reaction product of the present invention is not particularly limited. For example, in the above-mentioned mixing step, in addition to the free radical generating catalyst and free radical generating source of the present invention, the above-mentioned oxide and the above-mentioned oxidant can be further mixed. At this time, as mentioned above, it is preferred to further mix the solvent. And, in the above-mentioned free radical production step, the above-mentioned oxide and the oxidant can react by the action of the generated free radicals, thereby generating the above-mentioned oxidation reaction product. That is, the above-mentioned oxidation reaction step can be balanced with the above-mentioned free radical production step and carried out simultaneously in the same reaction system. In this case, the concentrations of the above-mentioned oxide and the above-mentioned oxidant are not particularly limited, and relative to the above-mentioned solvent, for example, the reaction mol·L is not particularly limited and can be appropriately set. In addition, for example, when the concentration of the above-mentioned oxide is high, the reaction speed is fast, so it is preferably as high as possible, and the concentration of the above-mentioned oxidant is easy to react, so it is preferably not too high. Among them, this description is an example and does not limit the present invention in any way.

[0109] In the method for producing an oxidation reaction product of the present invention, the free radical can also serve as the oxidant. For example, the free radical generator is an oxyacid, and the free radical generated by the oxyacid can also serve as the oxidant. For example, the free radical generator is a chlorite ion ClO2 - , or the chlorite ClO2 - Free radical ClO2 · The oxidation reaction product is produced by oxidizing the above-mentioned oxide as an oxidizing agent.

[0110] In addition, for example, the free radical and the oxidant may be different. For example, the free radical generator is the electron donor·acceptor linked molecule, and the oxidant is oxygen molecule O2, and the oxidation reaction product can be manufactured by oxidizing the oxide through the action of the free radical of the electron donor·acceptor linked molecule and the oxygen molecule.

[0111] The above-mentioned oxidized substance is not particularly limited, and can be, for example, an organic compound or an inorganic substance. For example, the above-mentioned oxidized substance can be triphenylphosphine Ph3P, and the above-mentioned oxidation reaction product can be triphenylphosphine oxide Ph3P=O. In addition, for example, the above-mentioned oxidized substance can be an olefin, and the above-mentioned oxidation reaction product can contain at least one of an epoxide and a diol.

[0112] The above-mentioned oxidized compound may be, for example, an aromatic compound (hereinafter sometimes referred to as "raw material aromatic compound"). In the present invention, the above-mentioned raw material aromatic compound is not particularly limited. If an electron-donating group is bonded to the aromatic ring of the above-mentioned raw material aromatic compound, it is easy to carry out, for example, an oxidation reaction (including oxidative substitution reaction) of the above-mentioned raw material aromatic compound, so it is preferred. The above-mentioned electron-donating group may be one or more, and is preferably a group with strong electron-donating property. More specifically, the above-mentioned raw material aromatic compound is more preferably covalently bonded to the aromatic ring with a group selected from -OR 100 、-NR 200 2 and Ar 100 At least one substituent in 100 is a hydrogen atom or any substituent, R 100 In the case of multiple R 100 The above R 200 is a hydrogen atom or any substituent, each R 200 They may be the same or different. 100 is aryl, Ar 100 In the case of multiple Ar 100 Can be the same or different.

[0113] The above Ar 100 It may be a group derived from any aromatic ring such as a benzene ring, a naphthalene ring, an anthracene ring, a phenanthrene ring, a pyridine ring, a thiophene ring, a pyrene ring, etc. The aromatic ring may further have one or more substituents on the ring, and the substituents may be the same or different. 100 For example, a phenyl group etc. are mentioned.

[0114] In addition, the above R 100 Preferably, it is at least one selected from a hydrogen atom, an alkyl group, an aryl group and an acyl group. The alkyl group is preferably a straight-chain or branched alkyl group having 1 to 6 carbon atoms, and a methyl group is particularly preferred. The acyl group is preferably a straight-chain or branched acyl group having 1 to 6 carbon atoms. The aryl group is, for example, the same as the Ar 100 The same, for example, is phenyl.

[0115] In addition, the above R 200 Preferably, it is at least one selected from a hydrogen atom, an alkyl group, an aryl group and an acyl group. The alkyl group is preferably a straight-chain or branched alkyl group having 1 to 6 carbon atoms, and a methyl group is particularly preferred. The acyl group is preferably a straight-chain or branched acyl group having 1 to 6 carbon atoms. The aryl group is, for example, the same as the Ar 100 The same as above, for example, is phenyl. 200 2. An amino group substituted with an electron donating substituent such as a dimethylamino group or a diphenylamino group is preferred because of its particularly high electron donating property.

[0116] In addition, the raw material aromatic compound, for example, has a substituent such as an alkyl group covalently bonded to the aromatic ring, and the substituent can be oxidized by the oxidation reaction product generation step. For example, the oxidant contains an oxygen atom, and the raw material aromatic compound contains a methylene group (-CH2-) covalently bonded to the aromatic ring. In the oxidation reaction product generation step, the methylene group (-CH2-) can be oxidized and converted into a carbonyl group (-CO-). In this case, the atom or atomic group bonded to the methylene group and the carbonyl group is not particularly limited, and hydrogen atoms, alkyl groups, aryl groups, etc. can be cited. The alkyl group is preferably a straight chain or branched alkyl group having 1 to 6 carbon atoms. The alkyl group and aryl group can be further substituted by one or more substituents, and the substituents can be the same or different in the case of multiple groups. For example, if hydrogen is bonded to the methylene group, a methyl group (-CH3) is formed, and a formyl group (-CHO) is formed after oxidation. If a methyl group is bonded to the methylene group, an ethyl group (-CH2CH3) is formed, and an acetyl group (-COCH3) is formed after oxidation. If a phenyl group is bonded to the methylene group, a benzyl group (-CH2Ph) is formed, which is oxidized to form a benzoyl group (-COPh). In addition, for example, the substituent group covalently bonded to the aromatic ring (before oxidation) is a formyl group (-CHO), which can be oxidized to form a carboxyl group (-COOH).

[0117] In the method for producing an oxidation reaction product of the present invention, the above-mentioned oxidized substance may be, for example, an olefin, such as an aromatic olefin or an aliphatic olefin. The above-mentioned olefin may be, for example, an olefin represented by the following chemical formula (A1). In addition, the above-mentioned olefin oxidation reaction product is not particularly limited, and may contain at least one of an epoxide and a diol as shown in the following scheme A. In the following chemical formulas (A1), (A2) and (A3), R is each a hydrogen atom or an arbitrary substituent, and each R may be the same or different from each other. The above-mentioned arbitrary substituent is, for example, an alkyl group, an unsaturated aliphatic hydrocarbon group, an aryl group, a heteroaryl group, a halogen, a hydroxyl group (-OH), a mercapto group (-SH) or an alkylthio group (-SR, R is an alkyl group), which may be further substituted with a substituent or may not be substituted. The above-mentioned alkyl group is more preferably a straight-chain or branched alkyl group having 1 to 6 carbon atoms. In addition, the above-mentioned olefin as the oxidized substance may be an olefin containing only one olefin bond (carbon-carbon double bond) or an olefin containing multiple (more than 2) olefin bonds.

[0118]

[0119]

[0120] The olefin, for example, as described above, may be an aromatic olefin. That is, for example, in the chemical formula (A1), at least one of R may be an aromatic ring (aryl or heteroaryl). In addition, the aromatic olefin, for example, as described as the raw material aromatic compound, may be covalently bonded to the aromatic ring to a -OR 100 、-NR 200 2. Ar 100 At least one substituent in .

[0121] In the method for producing an olefin oxidation reaction product of the present invention, the olefin may be at least one selected from ethylene, propylene, styrene and butadiene. In addition, the oxidation reaction product may be at least one selected from epoxide and diol, for example, as described above. Examples thereof are shown in the following schemes A1 to A3. The following schemes A1 to A3 are illustrative, and in the present invention, the oxidation reaction of ethylene, propylene and styrene is not limited thereto.

[0122]

[0123] In the oxidation of olefins (e.g., olefins (A1) of the above scheme A), for example, by adjusting the concentration of at least one of the above Lewis acid and Bronsted acid, the above free radical generating source and the above oxidant, the generated oxidation reaction products can be produced separately. If these concentrations are, for example, low concentrations relative to the above oxidized substance, there is a tendency to easily obtain epoxides, and if they are high concentrations, there is a tendency to easily obtain diols, but the present invention is not limited thereto. In addition, for example, instead of the above concentrations, the generated oxidation reaction products can also be produced separately by the intensity of the reactivity of the free radical species generated by the above free radical generating source. For example, in the case of a weakly reactive free radical species, there is a tendency to easily obtain epoxides, and in the case of a highly reactive free radical species, there is a tendency to easily obtain diols, but the present invention is not limited thereto. It should be noted that the use of the above oxidation reaction products is not particularly limited. For example, in the case where the above oxidized substance (raw material aromatic compound) is styrene, styrene oxide can be used as an adhesive, and diols can be used as fragrances, etc. As described above, the epoxide and the diol are required for different uses. Therefore, if they can be produced separately by controlling the reaction conditions, the present invention can be applied to a wider range of uses.

[0124] [4. Medications] As described above, the agent of the present invention is characterized in that it contains a free radical generating catalyst and a free radical generating source, and the free radical generating catalyst is the free radical generating catalyst of the present invention. In the agent of the present invention, other constitutions and conditions are not particularly limited. It should be noted that the ammonium can also be a substance having at least one of the Lewis acidity and the Bronsted acidity.

[0125] According to the present invention, a drug having high safety and high bactericidal effect can be provided.

[0126] In addition, the drug of the present invention can be used as, for example, a drug for agricultural and livestock production. Hereinafter, the drug of the present invention that can be used as a drug for agricultural and livestock production may be referred to as "the drug for agricultural and livestock production of the present invention".

[0127] The agricultural and livestock medicine of the present invention has high safety and high bactericidal effect. Therefore, the agricultural and livestock medicine of the present invention is widely used for sterilization and deodorization in the agricultural and livestock industry, for example. In addition, the agricultural and livestock medicine of the present invention is not easy to cause corrosion, and even if it is used in metal, it is not easy to cause corrosion. Therefore, the agricultural and livestock medicine of the present invention can be used on objects including metals, for example.

[0128] The agent of the present invention may be, for example, a free radical generating catalyst that catalyzes the generation of free radicals from at least one free radical generating source selected from the group consisting of halous acid, halous acid ion, and halous acid salt.

[0129] In the agent of the present invention, for example, the Lewis acidity of the radical generating catalyst of the present invention is not particularly limited, and as described above, is, for example, 0.4 eV or more, 0.5 eV or more, or 0.6 eV or more, and is, for example, 20 eV or less.

[0130] The medicament of the present invention may be, for example, liquid, solid, or semisolid. In addition, the medicament of the present invention may be acidic or non-acidic, alkaline or non-alkaline, neutral or non-neutral.

[0131] The drug of the present invention may be, for example, a liquid drug, characterized in that: The invention comprises a free radical generating catalyst and at least one selected from a halous acid, a halite ion and a halite salt; The free radical generating catalyst of the present invention is a free radical generating catalyst that catalyzes the generation of free radicals from at least one free radical generating source selected from halous acid, halous acid ion and halous acid salt, and the Lewis acidity of the free radical generating catalyst is 0.4 eV or more; The above-mentioned liquid medicine is non-acidic.

[0132] In the agent of the present invention, the free radical generating source can be appropriately selected according to the application, for example, by considering the intensity of the reactivity of the free radical species. For example, hypochlorous acid, which has a strong reactivity, and chlorous acid, which has a slightly more stable reactivity than hypochlorous acid and whose reaction is easier to control, can be used according to the purpose.

[0133] In the agent of the present invention, the content of the above-mentioned free radical generating source (such as oxyacids, etc.) is not particularly limited, for example, it is 0.01 mass ppm or more, 0.05 mass ppm or more, 0.1 mass ppm or more, 1500 mass ppm or less, 1000 mass ppm or less or 250 mass ppm or less. The above-mentioned free radical generating source (such as oxyacids, etc.) is preferably mixed in the agent at 0.01 to 1500 mass ppm, more preferably 0.05 to 1000 mass ppm, and further preferably 0.1 to 250 mass ppm. It can be considered that the safety of the case with low concentration is high, so the concentration is preferably low. Among them, if it is too low, it may not be possible to obtain a bactericidal effect, etc. From the viewpoint of bactericidal effect, etc., the concentration of the above-mentioned free radical generating source is not particularly limited, and the higher the better.

[0134] In the agent of the present invention, the content of the free radical generating catalyst (such as ammonium, cationic surfactant, etc.) is not particularly limited, for example, 0.01 mass ppm or more, 0.05 mass ppm or more, 0.1 mass ppm or more, 1500 mass ppm or less, 1000 mass ppm or less, 500 mass ppm or less or 250 mass ppm or less. The free radical generating catalyst (such as ammonium, cationic surfactant, etc.) is preferably mixed in the agent at 0.01 to 1500 mass ppm, more preferably 0.05 to 1000 mass ppm, more preferably 0.05 to 500 mass ppm, and further preferably 0.1 to 250 mass ppm. It can be considered that the safety of the case with a low concentration is high, so the concentration is preferably low. Among them, if it is too low, it may not be possible to obtain a bactericidal effect, etc. In addition, from the viewpoint of preventing the bactericidal effect from being unable to be obtained due to micelle formation, the concentration of the free radical generating catalyst is preferably below the micelle critical concentration.

[0135] In the agent of the present invention, the concentration ratio of the radical generating source and the radical generating catalyst in the agent (radical generating source / radical generating catalyst) is not particularly limited and can be appropriately set.

[0136] In addition, the medicament of the present invention may further include other substances. As the above-mentioned other substances, for example, water, organic solvents, pH adjusting agents, buffers, etc. can be cited, and one can be used alone, or two or more (hereinafter the same) can be used. The above-mentioned water is not particularly limited, for example, preferably purified water, ion exchange water or pure water.

[0137] The agent of the present invention preferably contains at least one of water and an organic solvent. It should be noted that in the present invention, the "solvent" can dissolve the free radical generating catalyst, free radical generating source, etc. of the present invention, but it may not dissolve the free radical generating catalyst, free radical generating source, etc. of the present invention. For example, after the above-mentioned mixing step, the free radical generating catalyst and free radical generating source of the present invention can each be in a state of being dissolved in the above-mentioned solvent, or in a state of being dispersed or precipitated in the above-mentioned solvent. In addition, the agent of the present invention preferably uses water as a solvent for the free radical generating catalyst and free radical generating source of the present invention from the viewpoints of safety, cost, etc. As an organic solvent, for example, ketones such as acetone, nitrile solvents such as acetonitrile, alcohol solvents such as ethanol, etc. can be cited, and these solvents can be used alone or in combination of two or more. The type of the above-mentioned solvent can be used, for example, according to the solubility of the solute (for example, the free radical generating catalyst of the present invention, the free radical generating source, etc.).

[0138] The pH of the agent of the present invention is not particularly limited, and may be, for example, 4.0 or more, 4.5 or more, 5.0 or more, 5.5 or more, 6.0 or more, 6.5 or more, 7.0 or more, or 7.5 or more. In addition, the pH of the agent of the present invention may be, for example, 11.5 or less, 11.0 or less, 10.5 or less, 10.0 or less, 9.5 or less, 9.0 or less, 8.5 or less, 8.0 or less, or 7.5 or less.

[0139] The agent of the present invention can be prepared, for example, by mixing the above-mentioned free radical generating source, the above-mentioned free radical generating catalyst, and at least one of the above-mentioned water and organic solvent as required. For example, the agent of the present invention can be obtained as described in the embodiments described later, but is not limited thereto. In addition, in the agent, as described above, other substances other than the free radical generating source and the free radical generating catalyst can be mixed.

[0140] The agricultural and livestock medicine of the present invention preferably contains the above-mentioned water, for example, but may not contain the above-mentioned water. The mixing amount of the above-mentioned water in the above-mentioned agricultural and livestock medicine (water ratio) is not particularly limited. The above-mentioned water ratio can be set to the remainder of other components, for example. In addition, the above-mentioned agricultural and livestock medicine further contains the above-mentioned pH adjuster, buffer, etc. as other substances, for example, or may not contain the above-mentioned pH adjuster, buffer, etc.

[0141] The method of using the agent of the present invention is not particularly limited. For example, it can be used in the same manner as conventional fungicides, etc. Specifically, for example, the agent of the present invention can be sprayed or coated on the object. Specifically, for example, in the case of space deodorization, it can be used by spraying. In the case of use in the oral cavity, it can be made into an aqueous solution for easy gargling or rinsing. In the case of use for the disinfection of pressure sores, it can be coated on the affected area. On the affected areas such as cancer self-destructive wounds (self-destructive sores) and Trichophyton mentagrophytes, it can be infiltrated into absorbent cotton or gauze, etc., and contacted with the affected area. When used for finger disinfection, it can be made into an aqueous solution so that it can penetrate (fold in). Medical instruments, etc. can be spray-coated or immersed in an aqueous solution for cleaning. For the purpose of sterilization / prevention around beds, around tables, door handles, etc., they can also be coated on them.

[0142] (Fungicide) The agent of the present invention can be used as a fungicide, for example. In the past, various substances have been used as fungicides, but the bactericidal effect has been insufficient. There are substances whose bactericidal effect can be improved by increasing the concentration, but there are problems in terms of safety. The fungicide containing the agent of the present invention has a sufficient bactericidal effect even at a low concentration and has high safety.

[0143] (Fungicide for finger disinfection) The agent of the present invention can be used as a fungicide for finger disinfection for disinfecting hands or fingers, etc., for example. The fungicide for finger disinfection containing the agent of the present invention has a sufficient bactericidal effect even at a low concentration and has high safety.

[0144] (Deodorant) The agent of the present invention can be used as a deodorant, for example. Generally, fungicides such as ethanol used as fungicides do not have a deodorizing effect. Although chlorine dioxide has a deodorizing effect, its safety is extremely low. In addition, among other commercially available products, there are substances described as having bactericidal and deodorizing effects. For example, there are products that directly spray the agent on clothes, or spray the agent in rooms, toilets, cars, etc., to produce bactericidal and deodorizing effects. The bactericidal component of such products usually uses quaternary ammonium salts. However, generally used quaternary ammonium salts do not use a free radical generating source (such as an oxygen-containing acid, etc.), so if not set to a high concentration, it is mostly impossible to obtain a sufficient bactericidal effect, and there are problems such as stickiness after use. In addition, quaternary ammonium salts do not have a deodorizing effect, so a deodorizing component is mixed separately. As the deodorizing component, cyclodextrin is usually used, but cyclodextrin does not have the ability to decompose the components that cause odors, and only masks the components that cause odors and cannot remove the odor itself. In contrast, the deodorant containing the agent of the present invention has a high bactericidal effect, for example, and can decompose substances that are the source of odors, for example, and has a high deodorizing effect due to the above-mentioned mechanism of action.

[0145] (Antibacterial agent for metals) The agent of the present invention can be used as an antimicrobial agent for metal, for example. The antimicrobial agent containing the agent of the present invention has high safety, so it can be sprayed or applied on metal products in the kitchen, for example. In addition, the antimicrobial agent containing the agent of the present invention is not easy to cause corrosion, and is not easy to corrode even when used for metal.

[0146] (Oral Care Agent) The drug of the present invention can be used as an oral care agent, for example. The oral care agent containing the drug of the present invention is highly safe and therefore suitable for use in the oral cavity.

[0147] (Acne Treatment) The drug of the present invention can be used as, for example, an acne treatment drug. The acne treatment drug containing the drug of the present invention has high safety and can be applied to the face.

[0148] (Disinfectant for bedsores) The drug of the present invention can be used as a disinfectant for bedsores, for example. The disinfectant for bedsores containing the drug of the present invention is highly safe and can be applied to the body.

[0149] (Fungicide for fungi) The agent of the present invention can be used as a fungicide for disinfecting affected areas caused by fungi such as Trichophyton, for example.

[0150] (Bactericide for water purification) The agent of the present invention can kill bacteria such as Legionella generated in swimming pool water or bath water. It also does not corrode metals and does not generate gas. Therefore, the water purification disinfectant containing the agent of the present invention can be used safely.

[0151] Furthermore, the medicament of the present invention can be used for the following purposes, for example. As mentioned above, the medicament of the present invention is highly safe and has a high bactericidal effect. In addition, the medicament of the present invention can, for example, exert a deodorizing effect, etc. Therefore, the medicament of the present invention is useful, for example, for improving QOL (Quality of Life), etc.

[0152] As described above, the drug of the present invention can be used in the human body by taking advantage of its high safety. More specifically, it can be used for the following purposes, for example. (1) Prevention, treatment, and symptom relief of cystitis (2) Prevention, treatment, and symptom relief of candidiasis (including oral / vaginal washing) (2) Eye drops and eye washes (including use for diseases such as styes) (3) For ear and nose cleaning (otitis media, otitis externa, sinusitis, etc.) (4) Oral cleaning and PMTC (Professional mechanical tooth cleaning). This includes oral cleaning and PMTC for preventing aspiration pneumonia, and oral cleaning and PMTC for improving the QOL (Quality of Life) of the elderly or disabled. (5) Abdominal lavage (including treatment of peritonitis and peritoneal inoculation) (6) Colon cleansing (7) Disinfection and cleaning of skin tissues (8) Finger disinfection and cleaning (9) Disinfection, cleaning and wiping of the affected area (including the wound area) (10) Treatment of allergic dermatitis and other dermatitis (disinfection, cleaning, wiping of affected area, etc.) (11) Disinfection and cleaning of affected areas due to bacterial infection such as whitlow (perionychia), folliculitis, carbuncle, furuncle, etc.

[0153] In addition, the drug of the present invention can be used, for example, for comprehensive measures in the prevention and treatment of infectious diseases. Specifically, for example, as shown below. (1) Prevention of upper respiratory tract infectious diseases (including influenza, SARS, and MERS) (2) Food poisoning prevention (Norovirus, Salmonella, etc.) (3) Vomitus treatment (4) Inactivation of Hepatitis B and C Viruses (5) Prevention, treatment, and symptom relief of ulcerative colitis (6) Mold and fungus countermeasures (i.e., can also be used for countermeasures other than sterilization and virus removal) (7) Prevention, treatment, and symptom relief of oral ulcers (side effects of molecular targeted drugs, etc.) (8) Surgical, pre-operative and post-operative care (including cancer surgery, etc.) (9) Nursing of cancer-affected areas (including oral cavity, breast (Mammo), self-injury wounds, etc.)

[0154] Furthermore, the sterilizing agent of the present invention can be used, for example, for the following purposes by taking advantage of its sterilizing effect and high safety. (1) Denture cleaning (2) Bottle sterilization (3) Disinfection (to prevent infection) and deodorization of daily items that are touched by an unspecified number of people, such as tables and door handles (4) Sterilization and deodorization of public transportation facilities such as trains, airplanes, and buses (5) Comprehensive environmental disinfection in schools, kindergartens, and nurseries (including disinfection of tables, doors, shelves, switches, toys such as building blocks, etc., for infection prevention, etc.) (6) Sterilization of medical equipment (including cleaning and sterilization of the interior and pipelines of artificial dialyzers) (7) Wiping, cleaning, or washing of X-ray, CT, electrocardiogram, and other diagnostic equipment (8) Sterilization of diagnostic and surgical instruments (including metal and resin parts such as surgical knives)

[0155] Furthermore, the agent of the present invention utilizes the decomposition action of proteins and can be used for the following purposes, for example. (1) Contact lens preservation solution (2) Glasses cleaning fluid (3) Ultrasonic cleaning machine (4) Cleaning agent (5) Glass cleaning (including the front windshield)

[0156] Furthermore, the agent of the present invention can be used to deodorize the following odors by utilizing the deodorizing effect, for example. (1) Bad breath (2)Body odor (3) Fecal odor (4) Odors caused by chemicals, gases, etc. (including all odors from factories such as chemical factories and food factories) (5) Garbage related (6) Garbage containing water, garbage dumps, garbage collection trucks, recycling centers, incineration plants (7) Sewer pipe related (8) Pipelines, oil traps and other collection equipment (9) Cigarettes (10) Medical related (including use for the purpose of improving the patient's QOL. In addition, including deodorization of malodor caused by self-healing wounds) (11) Operating Room (12) Ward (13) Environmental odors (feces odor, wastewater) in chicken sheds, pig sheds, cow sheds, etc. (14) Meat Center (Slaughterhouse)

[0157] The medicament of the present invention can be used, for example, in vitro. As described above, the medicament of the present invention has high safety, and therefore can be used, for example, in vivo. The medicament of the present invention can be used, for example, in vivo, and the free radical generating catalyst can catalyze the generation of free radicals from the free radical generating source. The above-mentioned in vivo can be, for example, in the human body, but can also be in the body of an animal other than a human.

[0158] The medicament of the present invention can be used, for example, in the digestive organs. The medicament of the present invention can catalyze the generation of free radicals from the free radical generating source in the digestive organs. The digestive organs can be, for example, at least one selected from the oral cavity, pharynx, esophagus, stomach, duodenum, small intestine and large intestine. The digestive organs can be, for example, large intestine. The small intestine can be, for example, at least one selected from the duodenum, jejunum and ileum. The large intestine can be, for example, at least one selected from the cecum, colon and rectum. The medicament of the present invention can be used, for example, for sterilization in the digestive organs, induction of changes in intestinal flora, treatment of ulcerative colitis or suppression of symptoms, etc.

[0159] The agent of the present invention can be sprayed using, for example, a sprayer, a humidifier, etc. In this case, for example, in addition to the bactericidal effect on the sprayed object, a bactericidal effect and a deodorizing effect on the sprayer, humidifier, etc. can also be obtained. In addition, the agent of the present invention can be used for human use, but is not limited to this, and can also be used for animals other than humans. Specifically, for example, it can be used for deodorization of animals and for the prevention of infectious diseases such as avian influenza / swine flu. In addition, as uses for animals other than humans, for example, the same uses as those listed as the above-mentioned uses for humans (including human bodies) can be cited. Furthermore, as uses for animals other than humans, for example, there is the use as a drug for agricultural and livestock production described below.

[0160] As mentioned above, the agricultural and animal husbandry agent of the present invention is highly safe and has a high bactericidal effect. Therefore, the agricultural and animal husbandry agent can be used as an agricultural agent, an animal husbandry agent, etc. The agricultural agent can be used as an agricultural bactericide, an agricultural antiviral agent, an agricultural deodorant, an agricultural insecticide, an agricultural repellent, an agricultural soil improver, etc. In addition, the animal husbandry agent can be used as an animal husbandry bactericide, an animal husbandry antiviral agent, an animal husbandry deodorant, an animal husbandry insecticide, an animal husbandry repellent, an animal husbandry soil improver, etc. The agricultural and animal husbandry agent can be used for one purpose, or for two or more purposes.

[0161] Examples of the above-mentioned agriculture include rice cultivation and dryland cultivation. Examples of the above-mentioned dryland cultivation include vegetables such as cucumbers, tomatoes, onions, cabbages, and soybeans, potatoes such as potatoes, flowers such as dendrobiums, clematis, and wood fragrance flowers, fruits such as strawberries, and fertilizers. Examples of the above-mentioned livestock industry include industrial animals such as cattle, pigs, and chickens.

[0162] When the agricultural and livestock pesticide of the present invention is used for the above-mentioned rice planting, the agricultural and livestock pesticide can be used as, for example, a fungicide, an insecticide, a repellent, a soil conditioner, and the like. Specifically, for example, by using the agricultural and livestock pesticide when soaking rice seeds, the occurrence of stickiness can be prevented, and the water change operation can be reduced. In addition, for example, by using the agricultural and livestock pesticide when soaking seeds, germinating and sowing, rice blast, sheath blight, rice false smut, rice seedling disease, and the like can be prevented. For example, by spraying the agricultural and livestock pesticide in a rice field, the occurrence of stink bugs, pests, and the like in rice can be prevented. For example, by spraying the agricultural and livestock pesticide when plowing a rice field, the soil can be improved.

[0163] When the agricultural and livestock agent of the present invention is used for the above-mentioned dry land planting, the agricultural and livestock agent can be used as a fungicide, an antiviral agent, a soil conditioner, etc. Specifically, for example, by spraying the agricultural and livestock agent on the leaves of cucumbers, tomatoes or strawberries, powdery mildew, mosaic disease, etc. can be prevented. For example, by spraying the agricultural and livestock agent on the leaves of tomatoes, gray mold, leaf mold, etc. can be prevented. For example, by spraying the agricultural and livestock agent on the leaves of onions, red rust, etc. can be prevented. For example, by spraying the agricultural and livestock agent on the leaves of cabbage, root knot disease, etc. can be prevented. For example, by spraying the agricultural and livestock agent on a potato dry field that has been plowed with a tractor, etc., and plowing it again, continuous cropping obstacles, etc. can be prevented. For example, by immersing seed potatoes in the agricultural and livestock agent, the seed potatoes can be disinfected (sterilized). For example, by spraying the above agricultural and livestock pesticides on potato leaves several times during the period from potato germination to harvest, scab can be prevented. For example, by spraying the above agricultural and livestock pesticides on chrysanthemums, clematis, and wood fragrance flowers, powdery mildew can be prevented.

[0164] When the agricultural and livestock agent of the present invention is used in the above-mentioned livestock industry, the agricultural and livestock agent can be used as, for example, a bactericide, a deodorant, and the like. Specifically, for example, by using the agricultural and livestock agent as an impregnation agent for cattle, mastitis and the like can be prevented. For example, by using the agricultural and livestock agent for a hoof bath for cattle and applying it to the affected part of the hoof disease, hoof disease and the like can be prevented or treated. For example, by spraying the agricultural and livestock agent on cattle using a sprayer, etc., respiratory diseases, foot-and-mouth disease, and the like can be prevented. For example, by spraying the agricultural and livestock agent on cattle sheds, pig sheds, chicken sheds, etc. using a sprayer, etc., deodorization can be achieved. For example, by using the agricultural and livestock agent on eggs, disinfection (sterilization) can be performed.

[0165] The agricultural and livestock agent of the present invention can be sprayed (sprayed) on the above-mentioned object, or it can be applied, or it can be sprayed, or the above-mentioned object can be immersed in the above-mentioned agricultural and livestock agent. Specifically, for example, in the case of deodorizing a space, it can be used by spraying. For affected parts such as hoof disease, for example, it can be impregnated in absorbent cotton or gauze and applied to the affected part. When used for finger disinfection, for example, an aqueous solution can be made so that it can penetrate. Medical instruments and the like can be sprayed or immersed in an aqueous solution for cleaning. In the case of machinery such as automobiles, agricultural machinery, forklifts used in the above-mentioned livestock houses, for example, the above-mentioned agricultural and livestock agent is sprayed on the above-mentioned machinery, or the above-mentioned agricultural and livestock agent is used to clean the above-mentioned machinery. When used as a deodorizing measure for the above-mentioned industrial animals, it can be used, for example, by spraying with a sprayer or the like, or by spraying with a sprayer or the like. In addition, for example, it can be sterilized by applying it to eggs.

[0166] <Fungicides for agriculture and livestock> The agricultural and livestock fungicide of the present invention is characterized in that it contains the agricultural and livestock agent of the present invention. The agricultural and livestock agent of the present invention can be used as a fungicide, for example. In the past, various substances were used as fungicides, but the fungicidal effect was insufficient. There are also substances that can improve the fungicidal effect by increasing the concentration, but there are problems with safety. The agricultural and livestock fungicide containing the agricultural and livestock agent of the present invention has a sufficient fungicidal effect even at a low concentration and is highly safe.

[0167] <Finger disinfectant for agricultural and livestock use> The disinfectant for disinfecting fingers for farm and livestock of the present invention is characterized by comprising the above-mentioned agricultural and livestock agent of the present invention. The agricultural and livestock agent of the present invention can be used as, for example, an agricultural and livestock finger disinfectant for disinfecting hands or fingers. The agricultural and livestock finger disinfectant containing the agricultural and livestock agent of the present invention has a sufficient bactericidal effect even at a low concentration and is highly safe.

[0168] <Deodorant for agricultural and livestock products> The deodorant for agricultural and livestock products of the present invention is characterized in that it contains the agricultural and livestock products agent of the present invention. The agricultural and livestock products agent of the present invention can be used as an agricultural and livestock deodorant, for example. As a conventional bactericidal component, quaternary ammonium salts are generally used. If the quaternary ammonium salt is not set to a certain concentration, a sufficient bactericidal effect cannot be obtained in most cases, and there are problems with safety. In addition, quaternary ammonium salts have no deodorizing effect, so a deodorizing component is mixed separately. As a deodorizing component, cyclodextrin is generally used, but cyclodextrin does not have the ability to decompose components that are the cause of malodor, and only masks the components that are the cause of malodor, and cannot remove the malodor itself. The agricultural and livestock deodorant containing the agricultural and livestock products agent of the present invention, for example, has a high bactericidal effect, and can remove substances that are the source of malodor, and has a high deodorizing effect.

[0169] <Fungicides for agriculture and livestock against fungi> The fungicide for livestock and agricultural production against fungi of the present invention is characterized by comprising the above-mentioned fungicide for livestock and agricultural production of the present invention. The fungicide for livestock and agricultural production against fungi of the present invention can be used as a fungicide for disinfecting affected areas caused by fungi such as Trichophyton, for example.

[0170] <Agricultural and livestock water purifier> The water purifier for agricultural and livestock production of the present invention is characterized in that it contains the above-mentioned agricultural and livestock chemical of the present invention. The water purifier for agricultural and livestock production of the present invention can, for example, sterilize bacteria such as Legionella generated in the water used for agricultural and livestock production. In addition, the agricultural and livestock chemical of the present invention does not corrode metals and does not generate gas. Therefore, the water purifier for agricultural and livestock production containing the agricultural and livestock chemical of the present invention can be used safely. The water purifier for agricultural and livestock production of the present invention can, for example, be used to sterilize bacteria contained in water or to improve water quality. Therefore, the water purifier for agricultural and livestock production of the present invention can also be called, for example, a bactericide for agricultural and livestock water or a water quality improver for agricultural and livestock water.

[0171] <How to use agricultural and livestock drugs> The method for using the agricultural and livestock chemical of the present invention is characterized by comprising a step of contacting an object with the agricultural and livestock chemical of the present invention. According to the method for using the agricultural and livestock chemical of the present invention, for example, the object can be sterilized or deodorized. Example

[0172] Hereinafter, examples of the present invention will be described, but the present invention is not limited to the following examples.

[0173] [Reference Example 1] In this reference example, it was confirmed that styrene can be efficiently dihydroxylated by using scandium trifluoromethanesulfonate and sodium chlorite. Specifically, at room temperature and pressure, a reaction was carried out based on scandium trifluoromethanesulfonate and chlorite (ClO2 - ) can efficiently produce 1-phenylethane-1,2-diol by dihydroxylation of styrene. It has been confirmed that scandium trifluoromethanesulfonate acts as a strong Lewis acid, and the chlorite ion (ClO2 - ) generates chlorine dioxide free radicals (ClO2 · ), while increasing the chlorine dioxide free radical (ClO2 · )'s reactivity.

[0174] In fine or specialty chemistry, the oxidation of olefins to 1,2-diols is an important industrial process for the production of precursors for a wide variety of chemical products, such as resins, pharmaceuticals, dyes, pesticides, and fragrance compositions. Various methods have been reported for the oxidation of olefins to the corresponding epoxides and alcohols, using inorganic metal oxo complexes and heavy metal oxides. VIII O4 is an effective and selective oxidizing agent for the conversion of olefins to 1,2-diols (references 1 to 8). However, the toxicity and sublimation of osmium compounds and their waste are serious problems. Sodium chlorite (NaClO2) is a non-toxic and inexpensive oxidizing agent that can be used as a chlorine dioxide radical (ClO2 · ) and used as a precursor (references 9 to 12 [same as non-patent documents 1 to 4]). It is known that ClO2 · It is a reactive and stable free radical. However, ClO2 · It is a yellow explosive gas at room temperature. · It can be prepared by oxidation of NaClO2 with Cl2 and reaction of potassium chlorate (KClO3) with oxalic acid (Reference 13). The toxicity of Cl2 and ClO3 in these methods is - The explosiveness of ClO2 may become a problem. · The precursor of NaClO2 is used for the epoxidation of olefins. · The oxidizing ability of ClO2 is not enough to oxidize olefins to diols in the absence of acid, so 1,2-diol products cannot be obtained (references 14 to 17). · Activation of the Cl=O double bond is the key for the selective dihydroxylation of olefins in one step.

[0175] In this reference example, the use of scandium trifluoromethanesulfonate [Sc(OTf)3] as a Lewis acid (reference 18) to react with ClO2 · A method for efficiently synthesizing dihydroxylated styrene at room temperature and pressure by activation. The dihydroxylation mechanism is elucidated based on the detection of free radical intermediates using EPR and UV-Vis absorption spectroscopy.

[0176] In the reaction of styrene (2.0 mM) with NaClO2 (20 mM) in an aqueous MeCN solution (MeCN / H2O 1:1 v / v) at room temperature (25°C), dihydroxylation of styrene did not occur (refer to Figure 6 ). It should be explained that Figure 6 Indicates the use 1The above reaction was carried out using CD3CN / D2O (1:1 v / v) as the solvent for HNMR spectroscopy as MeCN / H2O. 1 The results of HNMR tracking of the reaction were as follows: 0.3 hours and 17 hours after the start of the reaction 1 HNMR spectrum. When the temperature was increased to 333K, no dihydroxylation product was formed, but epoxidation ( Figure 7 )(References 14, 19). Figure 7 The results of CD3CN / D2O (4:1 v / v) containing styrene (66 mM) and NaClO2 (200 mM) at 60 °C (333 K) after 0 and 25 hours. 1 HNMR spectrum. * indicates the peak derived from styrene oxide. In contrast, when CF3COOH (30 mM) as a Bronsted acid was added as an additive, no epoxide was formed after 17 hours of mixing. Instead, 1-phenylethane-1,2-diol (1) and 2-chloro-1-phenylethanol (2) were produced in yields of 15% and 69%, respectively [reaction formula (1)]. 1 These compounds were determined by HNMR spectroscopy ( Figure 8 )(References 20). It should be noted that Figure 8 The results show that the CD3CN / D2O (1:1 v / v) mixture containing styrene (2.0 mM), NaClO2 (20 mM) and Sc(OTf)3 (30 mM) was mixed at 25°C for 0.6 hours and 17 hours. 1 HNMR spectra. * Marks and The marks are peaks derived from 1-phenylethane-1,2-diol and 2-chloro-1-phenylethanol, respectively. When a strong Lewis acid, Sc(OTf)3 (30 mM) was used instead of CF3COOH, the yield of diol (1) increased significantly to 51% [see the table of reaction formula (1) below] ( Fig.19 )(References 21). It should be noted that Fig. 9 The results show that the concentration of styrene (2.0 mM), NaClO2 (20 mM) and CF3COOD (30 mM) in CD3CN / D2O (1:1 v / v) was 0.5 h and 17 h later. 1 HNMR spectra. * Marks and The markers are peaks derived from 1-phenylethane-1,2-diol and 2-chloro-1-phenylethanol, respectively.

[0177] UV-Vis absorption spectroscopy was used to clarify the reaction mechanism and detect reactive intermediates. Figure 1As shown, NaClO2 shows an absorption band at 260nm in aqueous solution. This absorption band disappears when Sc(OTf)3 (10mM) is added, and a new absorption band increases at 358nm. This absorption band is based on ClO2 · Identification (attribution) (references 22, 23). In the presence of CF3COOH, the same change in the absorption spectrum can also be observed (reference 24). The time-dependent change of the appearance of the absorption band at 358 nm is shown in Figure 1 . Figure 1 This is the UV + visible absorption spectrum of NaClO2 (5.0 mM) taken at 0, 4 and 16 hours after mixing with Sc(OTf)3 (10 mM) in an aqueous solution at 298K. In this figure, the horizontal axis is wavelength (nm) and the vertical axis is absorbance. In addition, Figure 2 (a) is Figure 1 The same reaction (Sc(OTf)3 (10 mM) and NaClO2 (5.0 mM) in aqueous solution (0.20 M acetate buffer pH 2.9) at 298 K) was carried out to form Sc 3+ (ClO2 · )) of UV-Vis absorption at 358 nm. In this figure, the horizontal axis is time (seconds) and the vertical axis is absorbance at 358 nm. Figure 2 (b) Yes Figure 2 (a) is a secondary plot of the measurement results. Time distribution ( Figure 2 (a)) and secondary drawing ( Figure 2 (b)) is in good agreement. Thus, using Sc(OTf)3 ClO2 · In the formation of bimolecular ClO2 - The rate constant for the dimeric reaction was determined to be 0.16 M from the slope of the straight line. -1 s -1 .

[0178] In the absence of matrix, no attenuation of the absorbance at 358 nm was observed, based on the ClO2 generated from NaClO2 using Sc(OTf)3 in MeCN at 298 K. · . Figure 3 (a) is the Sc in MeCN / H2O (1:1 v / v) solution at 298 K in the presence of styrene (30-90 mM). 3+ (ClO2 · ) is the time distribution of UV-Vis absorption at 358nm consumed by ClO2. In this figure, the horizontal axis is time (seconds) and the vertical axis is ClO2 ·concentration. (b) is a plot of the pseudo-first-order rate constant versus styrene concentration. In the presence of excess styrene, the decay rate follows the pseudo-first-order ( Figure 3 (a)). The pseudo-first-order rate constant (k) observed for the addition of dihydroxy obs ) increases linearly with the increase of styrene concentration ( Figure 3 (b)). ClO2 · The dimeric rate constant for the consumption of styrene was determined to be 1.9 × 10 -2 M -1 s -1 (Reference 25). To clarify the free radical structure, EPR (electronic paramagnetic resonance) measurement was performed. Pure ClO2 was prepared by refluxing a MeCN solution containing NaClO2 at 353K for 1 hour. · After cooling to 298K, the EPR spectrum was measured. As a result, at g = 2.0151 (± 0.0002), four ultrafine lines originating from unpaired electrons of Cl nuclei were confirmed, and characteristic isotropic signals were confirmed at the same time. ( 35 Cl and 37 Cl has I = 3 / 2, and each has the same magnetic moment of 0.821 and 0.683 ( Figure 4 (a)) (Reference 26). The G value changes significantly by adding CF3COOH (g = 2.0106) and Sc(OTf)3 (g = 2.0103) ( Figure 4 (b) and 4(c)). ClO2 · The ultrafine coupling constant of (a(Cl)=16.26G)CF3COOH(15.78G) and Sc(OTf)3(15.56G) decreases in the presence of (a(Cl)=16.26G)CF3COOH(15.78G) and Sc(OTf)3(15.56G) (reference 27). This indicates that: protons and Sc 3+ With ClO2 · bonding, thereby forming H + ClO2 · and Sc 3+ ClO2 · As a reaction intermediate for strongly dihydroxylating styrene (reference 28, etc.).

[0179] like Figure 5 As shown, ClO2 · , H + ClO2 · and Sc 3+ ClO2 ·Density functional theory (DFT) calculations were performed to predict the reaction mechanism for the dihydroxylation. Structural optimization was performed at the DFT CAM-B3LYP / 6-311+G(d,p) level of theoretical calculations. Figure 5 The bond length of the DFT-optimized structure obtained based on theoretical calculations at the CAM-B3LYP / 6-311+G(d,p) level (a) is ClO2 · , (b) is H + ClO2 · , (c) is Sc 3+ ClO2 · .ClO2 · The bond length of the Cl-O double bond is calculated as ( Figure 5 (a)). + ClO2 · In the calculation, the bond length of the Cl-O double bond is ( Figure 5 (b)). Figure 5 (c) represents ClO2 · In comparison, Sc 3 + ClO2 · The bond strength is also significantly weakened The cleavage of the Cl-O bond may generate ClO, a strong oxidant, in the presence of the substrate. · It is beneficial. It should be noted that Fig.10 is (a)H + ClO2 · and (b) Sc 3+ ClO2 · A plot of the spin distribution based on theoretical calculations at the CAM-B3LYP / 6-311+G(d,p) level.

[0180] Based on the above results, ClO2 · The mechanism of the dihydroxylation of styrene is shown in reaction equations (2) to (5) and Scheme 1. The disproportionation reaction of NaClO2 in H + or Sc 3+ occurs in the presence of ClO - and ClO3 - [Reaction formula (2)] (reference 29). ClO - Easy with ClO2 - Then, Cl2O2 is reacted with protons to generate Cl2O2 [reaction equation (3)]. - Reduction, generating ClO2 as a reactive species ·[Reaction (4)] The overall stoichiometric ratio is given in reaction (5). ClO2 · By + and Sc 3+ It is activated by acid bonding. + In the case of , based on DFT calculation (see above), no cleavage of the Cl-O bond occurs. + Oxidation of styrene by addition of ClO2 to the styrene double bond · In contrast, as shown in Scheme 1, by Sc 3+ ClO2 · Homolysis of the complex Sc 3+ Cl-O bond is broken to generate ClO · and Sc 3+ O · , and add to the double bond of styrene, thereby utilizing Sc 3+ The scandium complex is then hydrolyzed to give the final product, diol and Sc 3+ C1O · (Scheme 1). 3+ C1O · Based on a large excess of ClO2 - Sc can be formed in the oxidation of 3+ ClO2 · And reuse. - As shown in reaction formula (2), ClO2 - Addition of Sc to the β-carbon of styrene 3+ ClO2 · The Cl-O bond is broken to form ClO · Two isomers are provided. In the case of bonding to form the beta carbon-ClO, as shown in Scheme 1, a chlorine compound is obtained as a final minor product.

[0181] C1O - +ClO2 - +2H + →Cl2O2+H2O (3) Cl2O2+ClO2 - →2ClO2 · +Cl - (4) 4ClO2 - +2H + →2ClO2 · +ClO3 - +Cl - +H2O (5)

[0182]

[0183] As shown above, according to this reference example, it can be confirmed that ClO2 · As Sc 3+ The Lewis acid in the presence of is an effective dihydroxylation agent for styrene. According to the present invention, a unique dihydroxylation route for olefins without hazardous wastes such as heavy metals can be provided.

[0184] [References, etc.] 1M.Schroeder,Chem.Rev.,1980,80,187-213. 2(a)ENJacobsen,I.Marko,WSMungall,G.Schroeder and KBSharpless,J.Am.Chem.Soc.,1988,110,1968-1970;(b)SGHentges and KBSharpless,J.Am.Chem.Soc.,1980,102,4263-4265. 3W. Yu, Y. Mei, Y. Kang, Z. Hua and Z. Jin, Org. Lett., 2004, 6, 3217-3219. 4(a)AJDelMonte,J.Haller,KNHouuk,KBSharpless,DASingleton,T.Strassner,andAAThomas,J.Am.Chem.Soc.,1997,119,9907-9908.(b)JSMWai,I.Marko,JSSvendsen,MGFinn,ENJacobsen and KB Sharpless, J. Am. Chem. Soc., 1989, 111, 1123-1125. 5(a)S.Kobayashi,M.Endo and S.Nagayama,J.Am.Chem.Soc.,1999,121,11229-11230; (b)S.Kobayashi,T.Ishida and R.Akiyama,Org.Lett.,2001,3,2649-2652. 6H.C.Kolb,P.G.Andersson and K.B.Sharpless,J.Am.Chem.Soc.,1994,116,1278-1291. 7E.J.Corey and M.C.Noe,J.Am.Chem.Soc.,1996,118,11038-11053. 8S.Y.Jonsson,K.Faernegrdh and J.-E.Baeckvall,J.Am.Chem.Soc.,2001,123,1365-1371. 9H.Dodgen and H.Taube,J.Am.Chem.Soc.,1949,71,2501-2504. 10J.K.Leigh,J.Rajput,and D.E.Richardson,Inorg.Chem.,2014,53,6715-6727. 11C.L.Latshaw,Tappi,1994,163-166. 12(a)J.J.Leddy,in Riegel's Handbook of Industrial Chemistry,8 th edn.Ed.,J.A.Kent,Van Nostrand Reinhold Co.Inc,New York,1983,pp.212-235;(b)I.Fabian,Coord.Chem.Rev.,2001,216-217,449-472. 13M.J.Masschelen,J.Am.Works Assoc.,1984,76,70-76. 14X.-L.Geng,Z.Wang,X.-Q.Li,and C.Zhang J.Org.Chem.,2005,70,9610-9613 15A.Jangam and D.E.Richardson,Tetrahedron Lett.,2010,51,6481-6484. 16J.J.Kolar and B.O.Lindgren,Acta Chem.Scand.B,1982,36,599-605. 17B.O.Lindgren,T.Nilsson,Acta Chem.Scand.B,1974,28,847-852. 18(a)S.Fukuzumi and K.Ohkubo,J.Am.Chem.Soc.,2002,124,10270-10271; (b)S.Fukuzumi and K.Ohkubo,Chem.-Eur.J.,2000,6,4532-4535. 19 The epoxidation of styrene (66 mM) with NaClO2 (200 mM) was studied in a MeCN / H2O (4:1 v / v) mixed solution at 333 K (reference 14, etc.). The yield of styrene oxide was 44% and the conversion of styrene was 61%. 20E.V.Bakhmutova-Albert,DWMargerum,JGAuer and BMApplegate,Inorg.Chem.,2008,47,2205-2211. 21 exploit 1 As a result of H NMR confirmation, no styrene epoxide was observed as an intermediate in the reaction using CF3COOH or Sc(OTf)3. 22C. Rav-Acha, E. Choushen (Goldstein) and S. Sarel, Helv. Chim. Acta, 1986, 69, 1728-1733. 23ClO2 · In aqueous solution, it is generated from acetic anhydride and NaClO2 (reference 22). · Exists in protonated form (H + ClO2 · ) possibility. 24W.Masschelein,Ind.Eng.Chem.Prod.Res.Devel.,1967,6,137-142. 25 This value is similar to that of ClO2 · The conversion of styrene to epoxide (1.17×10 -2 M -1 s -1 )(Reference 10) is slightly larger than that. 26(a)T.Ozawa and T.Kwan, Chem.Pharm.Bull.,1983,31,2864-2867; (b)T.Ozawa,T.Trends Org.Chem.,1991,2,51-58. 27 will Sc 3+ ClO2 · and H+ClO2 · The calculated values ​​of the spin distribution are shown in Figure 5 According to this, Sc and H nuclei show no spin density. It means that the EPR spectrum does not show hyperfine splitting originating from Sc (I=7 / 2) or H (I=1 / 2). 28 About Sc 3+ The bonding with the oxo group of the metal oxo complex is as follows: (a)J.Chen,X.Wu,KMDavis,Y.-M.Lee,MSSeo,K.-B.Cho,H.Yoon,YJPark,S.Fukuzumi,YNPushkar and W.Nam,J.Am.Chem.Soc.,2013,135,6388-6391; (b)H.Yoon,Y.-M.Lee,X.Wu,K.-B.Cho,YNPushkar,W.Nam and S. Fukuzumi, J. Am. Chem. Soc., 2013, 135, 9186-9194; (c) S. Fukuzumi, K. Ohkubo, Y.-M. Lee and W. Nam, Chem.-Eur. J., 2015, 21, 17548-17559. 29 About using Sc 3+ For the disproportionation of neutral free radicals, please refer to I. Nakanishi, T. Kawashima, K. Ohkubo, T. Waki, Y. Uto, T. Kamada, T. Ozawa, K. Matsumoto and S. Fukuzumi, S. Chem. Commun., 2014, 50, 814-816.

[0185] [Example 1] In this embodiment, activation of oxygen reduction reaction using benzethonium chloride is performed. Lewis acid has been extensively researched and developed in various organic synthesis reactions. Most of them are devoted to the research of using metal ions or metal complexes as Lewis acid points and the design of ligands around them. In this embodiment, benzethonium chloride is used as an ammonium derivative with strong Lewis acidity, and it is confirmed that it is widely useful in the oxidation reaction of aromatic organic compounds using sodium chlorite.

[0186] In acetonitrile, in the presence of tetraphenylporphyrin cobalt (II) complex Co(II)TPP (TPP = 5,10,15,20-tetraphenylporphyrin) (E ox =0.35V vs SCE) and molecular oxygen (E red =-0.86 V vs SCE), no electron transfer occurs. However, if the oxygen saturated solution ([CoTPP] = 9.0 × 10 -6 M, [O2] = 13 mM) was added with benzethonium chloride (Bzn + )([Bzn + Cl - ]=30mM), the absorption band derived from Co(II)TPP at 411nm was observed to be attenuated, and the absorption band characteristic of Co(III)TPP+ at 433nm with an absorption point was increased ( Fig.11 (a)). It should be noted that Fig.11 (a) is a graph showing the change of the ultraviolet + visible light absorption spectrum of the above solution over time, with the horizontal axis being the wavelength (nm) and the vertical axis being the absorbance. It is believed that the electron transfer reaction from Co(II)TPP to molecular oxygen occurs to generate Co(III)TPP + The time constants of the decay of the absorption band at 411 nm and the increase of the absorption band at 433 nm are almost consistent. According to pseudo-first-order curve fitting, the rate constant is determined to be 9.3×10 -5 s -1 ( Figure 2 (b)). Fig.11 In the graph of (b), the horizontal axis is time and the vertical axis is absorbance. + The concentration showed a linear dependence, and the catalyst migration rate constant (k cat ) is 0.24M -2 s -1 According to previous studies (Ohkubo, K.; Fukuzumi, S. Chem. Eur. J., 2000, 6, 4532), the electron transfer reaction from Co(II)TPP to molecular oxygen is carried out efficiently in the presence of Lewis acids such as metal ions. It is believed that the Bzn used in this study + The Lewis acid catalyzed reaction was also carried out in the case of + The catalytic rate constant (0.24M -2 s -1 ) is slightly lower than lithium perchlorate (0.36) and higher than strontium perchlorate (0.10M -2 s -1) and barium perchlorate (0.051M -2 s -1 ) value. Based on the above results, it can be considered that Bzn + It has strong Lewis acidity. The ΔE value, which is an indicator of Lewis acidity, was determined to be 0.53 eV by using the catalytic rate constant and the method described in the literature. In fact, there are reports that ammonium salts function as Lewis acids, for example, a value greater than that of ammonium hexafluorophosphate (NH4PF6) (0.32 eV) (reference 33, etc.), which confirms that this ammonium salt shows strong Lewis acidity among ammonium salts. It should be noted that Fig.21 In the diagram, benzethonium chloride [Bzn + Cl - ] and the Lewis acidity of various metal complexes. In this figure, the horizontal axis is the above-mentioned ΔE value (eV), and the vertical axis is the logarithm of the rate constant (log (k cat ,M -2 s -1 )).

[0187] Bzn was calculated by density functional theory (B3LYP / 6-31G(d) level) + The structure of is optimized. Fig.12 As shown in this figure, the Mulliken charge and LUMO orbital are localized near the ammonium nitrogen, thus predicting that Bzn + Shows Lewis acidity.

[0188] [Reference Example 2] In this example, the accelerating effect of the disproportionation reaction of NaClO2 by Lewis acid was confirmed.

[0189] As confirmed in Reference Example 1, sodium chlorite (NaClO2) is very stable in a neutral aqueous solution / acetonitrile mixed solution, so no decomposition is observed. If Sc(OTf)3 (40 mM) is added to a 20 mM solution thereof, ClO2 free radicals (ClO2 · )'s characteristic absorption band increases ( Fig.13 ). In this figure, the horizontal axis is wavelength (nm) and the vertical axis is absorbance. The increase of this absorption band is as shown in Reference Example 1 ( Figure 1 ) has been confirmed in the literature, if the concentration of Sc(OTf)3 is reduced, it can be observed as a time-dependent change. Similar studies have been conducted on magnesium ions and lithium ions, etc., which have a Lewis acidity lower than that of scandium ions, and the reaction rate constants have been determined for each. It is known that Lewis acids catalyze various disproportionation reactions. It can be considered that in this reaction, the same mechanism is used to convert ClO2 into 2-chloro-2-nitrogen according to reaction formula (2) of reference example 1. - Disproportionate to ClO- and ClO3 - Then, it can be considered that the generated ClO - In the presence of acid with a large excess of ClO2 - Reaction to provide Cl2O2 (Reaction formula (3) of Reference Example 1). Then, it is believed that Cl2O2 further reacts with ClO2 - The reaction provides ClO2 radicals as active radical species (Reaction formula (4) of Reference Example 1).

[0190] [Example 2] In this example, the use of benzethonium chloride to promote ClO2 radical generation and oxidation reaction was confirmed.

[0191] First, since ClO2 radicals are believed to exhibit strong oxidative activity, 10-methyl-9,10-dihydroacridine (AcrH2) (1.4 mM) and sodium chlorite (NaClO2) (2.8 mM) were added to a mixed solution of deoxyacetonitrile / water (1:1 v / v). In this case, the oxidation reaction of AcrH2 hardly proceeded ( Fig.14 ). Fig.14 The graphs (a) to (c) show the changes over time in the above reaction. Fig.14 In (a), the horizontal axis is wavelength (nm) and the vertical axis is absorbance. Fig.14 (b) is a graph showing the change over time of absorbance at a wavelength of 358 nm, where the horizontal axis represents time (seconds) and the vertical axis represents absorbance. Fig.14 (c) is a graph showing the change over time of absorbance at a wavelength of 387 nm, where the horizontal axis represents time (seconds) and the vertical axis represents absorbance.

[0192] Then, with Fig.14 The mixed solution was prepared in the same way. If Bzn was further added + (0.56 mM), then the oxidation reaction from AcrH2 to 10-methylacridone was carried out ( Fig.15 ). Fig.15 The graphs (a) and (b) show the changes over time in the above reaction. Fig.15 In (a), the horizontal axis is wavelength (nm) and the vertical axis is absorbance. Fig.15 (b) is a graph showing the time-dependent change of absorbance at a wavelength of 387 nm, with the horizontal axis being time (seconds) and the vertical axis being absorbance. Fig.15 As shown in (a) and (b), the 10-methylacridone (λ max =382 nm) with time, it was confirmed that the oxidation (oxidation) reaction of AcrH2 to 10-methylacridone was proceeding.

[0193] In addition, even with Fig.15Similarly, scandium trifluoromethanesulfonate (Sc(OTf)3, 3.0 mM) was further added to the mixed solution, and the oxidation reaction of AcrH2 to 10-methylacridone was also carried out ( Fig.16 ). Fig.16 The graphs (a) and (b) show the changes over time in the above reaction. Fig.16 In (a), the horizontal axis is wavelength (nm) and the vertical axis is absorbance. Fig.16 (b) is a graph showing the time-dependent change of absorbance at a wavelength of 430 nm, with the horizontal axis being time (seconds) and the vertical axis being absorbance. Fig.16 As shown in (a) and (b), the absorption increase derived from 10-methylacridone was observed over time, so it can be confirmed that the oxidation (oxidation) reaction of AcrH2 to 10-methylacridone is proceeding. It is believed that this oxidation reaction is carried out by Fig.17 That is, it can be considered that ClO2 · Acridone is obtained by removing hydrogen from 10-methylacridone and adding oxygen. On the other hand, it is believed that the product after adding oxygen, i.e., ClO · With ClO2 - An electron transfer reaction occurs to provide ClO - and ClO2 · Thus regeneration.

[0194] [Reference Example 3] In this reference example, it was confirmed that the oxidation reaction of the substrate using NaClO2 using Lewis acid is useful for the oxidation reaction from triphenylphosphine to triphenylphosphine oxide. More specifically, it was confirmed that the oxidation reaction from triphenylphosphine to triphenylphosphine oxide using NaClO2 was carried out in the presence and absence of scandium trifluoromethanesulfonate Sc(OTf)3 as Lewis acid, and the Lewis acid promoted the reaction.

[0195] First, the reaction was carried out under the following conditions in the presence or absence of Sc(OTf) 3 at room temperature and pressure (without light irradiation), and the reaction was followed by ultraviolet-visible absorption spectroscopy. Fig. 22 The ultraviolet-visible absorption spectrum of (a) shows the conversion of triphenylphosphine into triphenylphosphine oxide by time-dependent changes. In this figure, the horizontal axis is wavelength (nm) and the vertical axis is absorbance. In addition, Fig. 22 (b) shows the graph of Sc(OTf)3(Sc 3+ ) in the presence and absence of triphenylphosphine (Ph3P) concentration over time. The horizontal axis is time (seconds) and the vertical axis is triphenylphosphine (Ph3P) concentration (mM). As shown in the figure, the reaction rate constant k calculated from the curve is in the absence of Sc 3+ In the case of 9.8×10 -4 S -1In contrast, in Sc 3+ In the presence of -3 S -1 , so it can be confirmed that Sc 3+ (Lewis acid) promotes the reaction. [Ph3P]=0.4mM [NaClO2]=0.4mM Sc(OTf)3=0 or 10 mM 0.12M acetate buffer pH 5.3 MeCN / H2O(4:6)

[0196] In addition, in deoxyacetonitrile MeCN / H2O (0.9ml / 0.1ml), even if triphenylphosphine and NaClO2 (4.0mM) were mixed, the reaction did not proceed at all. If scandium trifluoromethanesulfonate Sc(OTf)3 (30mM) was added thereto, an oxidation product was provided efficiently. The above reaction was carried out at 25°C for 15 minutes at the initial concentration of triphenylphosphine, varying from 1.0mM, 2.0mM, 4.0mM, and 8.0mM. The reaction was followed by the spectral changes of the UV-visible absorption spectrum ( Fig.18 (a)). Fig.18 In (a), the horizontal axis is wavelength (nm) and the vertical axis is absorbance. 3+ The ClO2 radical is generated as an active radical species, and Ph3P is oxidized to Ph3P=O. The stoichiometric ratio is shown in the following reaction formula (6), and it can be confirmed that the reaction proceeds almost quantitatively ( Fig.18 (b)). Fig.18 In (b), the horizontal axis is the initial concentration of Ph3P, and the vertical axis is the concentration of generated Ph3P=O. 2Ph3P+NaClO2 --> 2Ph3P=O+NaCl (6)

[0197] [Reference Example 4] In this reference example, in acetonitrile, in 9- 10-Methylacridine (Acr + -Mes) perchlorate (Acr + -MesClO4 - ) and oxygen, an oxidation reaction of the raw material aromatic compound (benzaldehyde) is carried out to obtain an oxidation reaction product (benzoic acid) ( Fig. 20 ). Reaction in Bzn + Cl - It was carried out in the presence and absence of .

[0198] As the reaction solvent, 0.6 mL of CD3CN saturated with oxygen was used, such as Fig. 20 As shown, add Acr + -MesClO4 - 1mM, benzaldehyde (PhCHO) 5mM, Bzn + Cl - 0 or 1mM, irradiated with 390nm wavelength light by xenon lamp or not. 1 The reaction was followed by HNMR. The results are shown in Fig. 20 In the table, “×” indicates that no reagent was added or no light was irradiated. “○” indicates that light was irradiated. “conversion” is the conversion rate of the raw material aromatic compound (benzaldehyde), and “yield” is the yield of benzoic acid. “time” is the reaction time. Fig. 20 As shown, without adding Bzn + Cl - In the case of adding Bzn + Cl - In the case of , the yield of benzoic acid was 60%, and the conversion rate of benzaldehyde was 63%. + -Mes in Lewis acid (Bzn + Cl - ) is not present, but is less reactive in the presence of a Lewis acid (Bzn + Cl - ) promotes the + -Mes free radicals are generated, forming a powerful reactant.

[0199] [Reference Example 5] In this reference example, the oxidation reaction product of tetraphenylporphyrin cobalt was prepared by the determination method described in the above "Determination method of Lewis acidity", using various ammonium as a free radical generating catalyst and oxygen molecules as a free radical generating source (also serving as an oxidant). That is, tetraphenylporphyrin cobalt, saturated O2 and a Lewis acidity determination object (such as a metal cation, wherein M in the following chemical reaction formula (1a) is represented by n+ The change in the ultraviolet-visible absorption spectrum was measured at room temperature to confirm that CoTPP was obtained as the oxidation reaction product. + .

[0200]

[0201] The above oxidation reaction was carried out using the ammonium compounds shown in the following table as free radical generating catalysts. cat ,M-2 s -1 The numerical value represented by “” is the reaction rate constant of CoTPP and oxygen in the presence of Lewis acid, which is an index of the Lewis acidity of each ammonium. The numerical value represented by “LUMO, eV” is the energy level of LUMO. In addition, “benzetoniumchloride” means benzethonium chloride, “benzalkonium chloride” means benzalkonium chloride, “tetramethylammonium hexafluorophosphate” means tetramethylammonium hexafluorophosphate, “tetrabutylammonium hexafluorophosphate” means tetrabutylammonium hexafluorophosphate, and “ammoniumhexafluorophosphate” means ammonium hexafluorophosphate.

[0202]

Table tpp

[0203] [Examples of Drugs] Next, specific examples of the drug of the present invention are described. However, the drug of the present invention is not limited to the following examples.

[0204] Embodiment 3: Dissolve 5g of sodium chlorite in purified water to make 100mL to obtain a 40,000 ppm sodium chlorite aqueous solution (liquid A). Dissolve 0.1g of benzethonium chloride in 100mL of purified water to make 100mL of a 1000ppm aqueous solution (liquid B). Prepare 0.1M phosphoric acid·NaOH buffer (pH=9.5). Add 20mL of liquid A diluted 10 times and 80mL of buffer to 600mL of purified water at pH7, then add 80mL of liquid B, add purified water to make 800mL, and obtain the agent involved in Example 3. The agent is an aqueous solution containing NaClO2 and benzethonium chloride. The pH of the agent involved in Example 3 manufactured in this way was measured, and the result was 7.5.

[0205] In addition, the NaClO2 concentration was set to 100mM, and the benzethonium chloride concentration was set to 1.0mM. The drug was manufactured in the same manner as the drug involved in Example 3. The drug was sealed in an ESR tube, and the ESR (Electron Spin Resonance) spectrum was measured at -196°C using an electron spin spectrophotometer (JES-ME-LX X-band [trade name] manufactured by JEOL Ltd.), and the generation of chlorine dioxide free radicals was confirmed. It should be noted that ESR and EPR (electronic paramagnetic resonance) have the same meaning. The measured ESR spectrum is shown in Fig.23 As shown in the figure, since a peak indicating the presence of free radicals appears, it can be confirmed that benzethonium chloride (benzethonium chloride), which is ammonium, acts as a free radical generation catalyst for sodium chlorite (NaClO2) to generate chlorine dioxide free radicals.

[0206] Embodiment 4: 5g of sodium chlorite is dissolved in purified water to make 100mL to obtain a 40,000 ppm sodium chlorite aqueous solution. 0.1g of benzethonium chloride is dissolved in 100mL of purified water to make a 1000ppm aqueous solution. The 40,000 ppm sodium chlorite aqueous solution is diluted 40 times to obtain a 1000ppm aqueous solution. 10mL of sodium chlorite aqueous solution and benzethonium chloride aqueous solution are taken respectively, mixed with 80mL of purified water to make a 100ppm aqueous solution to obtain the medicament (comprising NaClO2 and an aqueous solution of benzethonium chloride) involved in Example 4. The medicament of Example 4 thus obtained is measured for pH, and the result is 7.5. In addition, the medicament of Example 4 is carried out in the same manner as the medicament of Example 3, and the ESR spectrum is measured, and the result is the same, that is, benzethonium chloride (benzethonium chloride) plays a role as a free radical generation catalyst to sodium chlorite (NaClO2) to generate chlorine dioxide free radicals.

[0207] Comparative Example 1: A disinfectant containing sodium hypochlorite and water (commercially available product). Comparative Example 2: A bactericidal deodorant containing sodium hypochlorite (commercially available product). Comparative Example 3: A bactericidal deodorant containing hypochlorous acid and water (commercially available product). Comparative Example 4: A bactericidal deodorant containing sodium hypochlorite and water (commercially available product). Comparative Example 5: A bactericidal deodorant containing sodium hypochlorite and water (commercially available product). Comparative Example 6: Sodium chlorite standard solution 1000 ppm (test product).

[0208] Comparative Example 7: 5 g of sodium chlorite (produced by Wako Pure Chemical Industries, Ltd.) was dissolved in 100 mL of purified water to prepare a 40,000 ppm aqueous solution, which was further diluted with purified water to prepare a 100 ppm aqueous solution, thereby obtaining a test product of Comparative Example 7. Comparative Example 8: Benzethonium chloride aqueous solution (test product).

[0209] (Experimental Example 1) In Experimental Example 1, the following bacterial solution was first prepared. Use bacteria: Staphylococcus aureus Escherichia coli MV1184 Bacterial liquid: The bacteria grown in the BHI agar medium were collected with a platinum loop, placed in a BHI liquid medium and shaken. 50 μL of the bacterial solution grown in the BHI liquid medium for one day and night was diluted 190 times with the BHI liquid medium, mixed and stirred to prepare a bacterial solution.

[0210] Using the above bacterial solution, the effect (bactericidal action) was examined in the following manner.

[0211] Use a UV sterilizing lamp to sterilize the microplate (with a lid) for 10 minutes. Then, use a micropipette to inject BHI liquid culture medium, the above-mentioned bacterial solution and the agent involved in Example 3 into each well in turn. After culturing at 37°C for 24 hours, confirm with an enzyme marker and find the MIC (minimum inhibitory concentration). It should be noted that in the control, only the liquid culture medium was confirmed. In addition, 10μL of the culture solution was taken out from the well near the MIC, inoculated in a culture dish, and cultured at 37°C for 24 hours to find the MBC (minimum bactericidal concentration). The results are shown in Table 1.

[0212] The fungicide of Comparative Example 1 was used instead of the agent of Example 3, and the MIC and MBC were determined in the same manner. The results are shown in Table 1.

[0213] The MIC of Staphylococcus aureus was determined in the same manner using the bactericidal and deodorizing agents of Comparative Examples 2 to 5 instead of the agent of Example 3. The results are shown in Table 1.

[0214] The test product of Comparative Example 6 was used instead of the drug of Example 3, and the MIC of Staphylococcus aureus and the MIC and MBC of Escherichia coli were determined in the same manner. The results are shown in Table 1.

[0215]

Table 1

[0216] (Experimental Example 2) The MIC of Escherichia coli was determined in the same manner using the agent of Example 4 or Comparative Example 7 or 8 instead of the agent of Example 3. The results are shown in Table 2.

[0217]

Table 2

[0218] (Experimental Example 3) In Experimental Example 3, first, the following bacterial solution was prepared. Use bacteria: Streptococcus pyogenes Bacterial liquid: The same procedure as in Experimental Example 1 was performed to obtain a bacterial solution.

[0219] The above bacterial solution was used in the same manner as in Experimental Example 1, and the MIC and MBC were determined using the drug according to Example 3. The results are shown in Table 3.

[0220]

Table 3

[0221] (Experimental Example 4) In Experimental Example 4, the following bacterial solution was first prepared. Use bacteria: Streptococcus mutans Bacterial liquid: The bacteria grown in the BHI agar medium were collected with a platinum loop, added to the BHI liquid medium and shaken, and 50 μL of the bacterial solution grown in the BHI liquid medium for one day and night was diluted 190 times with the BHI liquid medium, mixed and stirred to prepare a bacterial solution.

[0222] Using the above bacterial solution, the effect was studied in the following manner.

[0223] Use a micropipette to inject the bacterial liquid into the BHI liquid culture medium added to two test tubes. Add sucrose in a manner to reach 0.2%. Cultivate at 37°C for 18 hours to form a biofilm. Discard the culture medium in the test tube into a beaker and wash twice with PBS. Inject the agent and PBS involved in Example 3 respectively, and shake at 37°C for 30 minutes. Discard the liquid in the test tube into a beaker and wash twice with PBS. Inject BHI liquid culture medium into the test tube and culture at 37°C for 24 hours. Inoculate 10μL of each culture medium into ordinary agar medium and culture at 37°C for 24 hours. Visually confirm the presence or absence of colonies. As a result, no colonies were confirmed in the case of injecting the agent involved in Example 3, but a large number of colonies were confirmed in the case of injecting PBS.

[0224] In order to confirm the effect on the bacterial cells inside the biofilm, the following confirmation test was further performed.

[0225] Use a micropipette to inject bacterial liquid into the BHI liquid culture medium added to the microtube. Add sucrose in a way that reaches 0.2%. Cultivate at 37°C for 18 hours to form a biofilm. Discard the culture medium in the microtube in a beaker and wash it twice with PBS. Inject the agent and PBS involved in Example 3 respectively, and culture (cultivate) at 37°C for 15 minutes and 30 minutes. Discard the liquid in the microtube in a beaker and wash it twice with PBS. Inject BHI liquid culture medium into the test tube, homogenize it, and culture it at 37°C for 24 hours. Inoculate 10μL of each culture medium into ordinary agar medium and culture it at 37°C for 24 hours. Confirm the presence or absence of colonies by visual inspection. As a result, no colonies were confirmed in the case of injecting the agent involved in Example 3, but a large number of colonies were confirmed in the case of injecting PBS. It can be seen from this that the agent involved in Example 3 acts by infiltrating into the biofilm until the inside of the biofilm, showing a bactericidal effect.

[0226] (Experimental Example 5) In Experimental Example 5, the following bacterial species were used, and the agent according to Example 3 was used in the same manner as in Experimental Example 1 to determine MIC and MBC. The results are shown in Table 4. Use bacteria: Bacteria 1 (Porphyromonas gingivalis) Bacteria 2 (Treponema denticola) Bacteria 3 (Tannerella fosythensis) Bacteria 4 (Aggregatibacter actinomycetemcomitans)

[0227]

Table 4

[0228] (Experimental Example 6) For iron, aluminum, tinplate and stainless steel, each test piece (25.4 mm × 25.4 mm) was washed, immersed in a resin container to which the reagent involved in Example 3, a 1.2% aqueous solution of sodium hypochlorite and tap water were added, and the resin container was covered. After each time recorded in Tables 5 and 6, the test piece was taken out onto a non-woven fabric and the condition of the test piece was visually confirmed. Confirmation was performed by taking photos as needed, and in addition, observation was performed under a microscope when changes were difficult to detect. The following criteria were used for evaluation.

[0229] -: No corrosion ±: Rust +: A certain amount of rust ++: Lots of rust +++: Corrosion of metal surface

[0230]

Table 5

[0231]

Table 6

[0232] (Experimental Example 7) Deodorization performance test was conducted in accordance with the Japan Electrical Manufacturers Association standard JEM1467 "Household air purifier". 3 In an acrylic container (1m long × 1m wide × 1m deep), start the stirrer, burn the cigarettes, and fill the container with smoke. After all the cigarettes have been burned, stop the stirrer, start the sprayer, spray the agent involved in Example 3, and measure the concentrations of the three components of ammonia, acetaldehyde and acetic acid in the container at regular intervals for 2 hours to track the concentration changes. Similarly, formaldehyde vapor is injected into the acrylic container, and the formaldehyde concentration in the container is measured at regular intervals for 2 hours to track the concentration changes. It should be noted that the sprayer is operated in 'Manual' mode. In addition, as a control, a blank test without operating the sprayer is carried out. The results are shown in Tables 7 to 10. The determination of the malodorous components is carried out by a detection tube (manufactured by GASTEC), and the detection tube used is shown below.

[0233] Use test tube Ammonia No.3L Acetaldehyde No.92L Acetic acid No.81L Formaldehyde No.91

[0234]

Table 7

[0235]

Table 8

[0236]

Table 9

[0237]

Table 10

[0238] (Experimental Example 8) The deodorizing performance of cigarette odor was measured by spraying the agent involved in Example 3 with a sprayer. First, a cigarette was burned in a room with a width equivalent to 6 tatami mats, so that the smoke filled the room and reached a certain concentration. Next, the sprayer was configured to measure the odor intensity in the room three times: before starting, 1 hour after starting, and 2 hours after starting. The sprayer was configured next to the wall of the room, and the odor was collected at a height of 1m in the center of the room. Two stirring fans were set in the room and set to a continuous stirring state. It should be noted that the sprayer was operated in 'Manual' mode. In addition, as a control, a blank test without operating the sprayer was carried out. The odor intensity was determined in the following manner using the 6-level odor intensity representation method. The results are shown in Table 11.

[0239] The testers (group) who evaluated the odor intensity were set to 6, and the intensity values ​​of each were averaged to calculate the result. The 6-level odor intensity expression is a method of numerically expressing the intensity of odor using human sense of smell. The group that conducted this test was people who had undergone the legal olfactory test and were certified to have normal sense of smell.

[0240] The following numerical values ​​are used as reference in the six-level odor intensity representation system. 0: No odor 1: Very weak odor (detection threshold concentration) 2: Weak odor (perception threshold concentration) 3: Easily detectable odor 4: Strong odor 5: Very strong odor

[0241]

Table 11

[0242] (Experimental Example 9) The agent involved in Example 3 was sprayed using a sprayer, and the removal performance of airborne bacteria (general bacteria and fungi) was measured. First, a sprayer was placed in a room with a width equivalent to 6 tatami mats, and the concentration of airborne bacteria in the air was measured three times: before startup, 1 hour after startup, and 2 hours after startup. The sprayer was placed next to the wall of the room, and the collection of airborne bacteria was set at a height of 1m in the center of the room. Two stirring fans were installed in the room and set to a continuous stirring state. The determination of airborne bacteria was carried out by the filtration capture method using a membrane filter. It should be noted that the sprayer was operated in 'Manual' mode. In addition, as a control, a blank test without starting the sprayer was carried out. The results are shown in Tables 12 and 13.

[0243] Measurement conditions etc. of Experimental Example 9 Filter used: Made by Toyo Filter Paper Co., Ltd., 37mm monitor Air suction volume: 300L (20L per minute for 15 minutes) Medium used: m-TGE Broth liquid medium for general bacteria (manufactured by Toyo Seisakusho) m-Green Y&M Broth liquid culture medium for fungi (manufactured by Toyo Seisakusho) Culture conditions: general bacteria 30℃ 72 hours Fungus 30℃ 5 days

[0244]

Table 12

[0245]

Table 13

[0246] (Experimental Example 10) In Experimental Example 10, the MIC or MBC was determined by using the drug according to Example 3 in the same manner as in Experimental Example 1 except that the following bacterial species were used. The results are shown in Table 14. Use bacteria: Streptococcus mutans Hemolytic Streptococcus Bacillus subtilis Candida albicans

[0247]

Table 14

[0248] (Experimental Example 11) According to the instrumental analysis implementation manual; detector tube method, gas chromatography ((Company) Fiber Evaluation Technology Council Deodorant Processed Fiber Product Certification Standards Approved), a deodorization test was conducted using the agent involved in Example 3. The results are shown in Table 15.

[0249]

Table 15

[0250] (Experimental Example 12) The drug of Example 3 was applied to acne, about 2 mL at a time, multiple times a day, for 14 days. The results showed that the application of the drug led to the cure of acne, confirming that the drug of the present invention is useful as an acne treatment drug.

[0251] Embodiment 5: The agent of Example 5 was manufactured in the same manner as in Example 3 except that half the mass (number of moles) of ammonium chloride (NH4Cl) was used instead of benzethonium chloride as ammonium. The pH of the agent of Example 5 was measured and the result was 7.5. Furthermore, the agent was manufactured in the same manner as in Example 5 except that the concentration of NaClO2 was set to 100 mM and the concentration of ammonium chloride (NH4Cl) was set to 0.5 mM. The ESR spectrum of the agent was measured in the same manner as in Example 3. The measured ESR spectrum is shown in FIG. Fig.24 As shown in the figure, a peak indicating the presence of free radicals appeared, and thus it was confirmed that ammonium chloride (NH4Cl) acted as a free radical generation catalyst on sodium chlorite (NaClO2) to generate chlorine dioxide free radicals.

[0252] Embodiment 6: As ammonium, the same amount (number of moles) of benzalkonium chloride (chemical formula below) was used instead of benzethonium chloride, and the same procedure as in Example 3 was followed to obtain the agent of Example 6. The pH of the agent of Example 6 was measured, and the result was 7.5. Furthermore, the agent was prepared in the same manner as in Example 6, except that the concentration of NaClO2 was set to 100 mM and the concentration of benzalkonium chloride was set to 1.0 mM. The ESR spectrum of the agent was measured in the same manner as in Example 3. The measured ESR spectrum is shown in FIG. Fig.25 As shown in the figure, a peak indicating the presence of free radicals appeared, and thus it was confirmed that benzalkonium chloride, which is ammonium, acted as a free radical generation catalyst on sodium chlorite (NaClO2) to generate chlorine dioxide free radicals.

[0253] Embodiment 7: The same method as in Example 3 was used to obtain the agent of Example 7 except that the same amount (number of moles) of benzyltriethylammonium chloride (chemical formula below) was used instead of benzethonium chloride as ammonium. The pH of the agent of Example 7 was measured and the result was 7.5. Furthermore, the agent was prepared in the same manner as in Example 3 except that the concentration of NaClO2 was set to 100 mM and the concentration of benzyltriethylammonium chloride was set to 1.0 mM. The ESR spectrum of the agent was measured in the same manner as in Example 3. The measured ESR spectrum is shown in FIG. Fig.26 As shown in the figure, a peak indicating the presence of free radicals appeared, and thus it was confirmed that benzyltriethylammonium chloride acted as a free radical generation catalyst on sodium chlorite (NaClO2) to generate chlorine dioxide free radicals.

[0254] Embodiment 8: As ammonium, methylammonium chloride of the same amount (number of moles) was used instead of benzethonium chloride, and the same method as in Example 3 was used to obtain the agent of Example 8. The pH of the agent of Example 8 was measured, and the result was 7.5. Further, the agent was manufactured in the same manner as in Example 3, except that the concentration of NaClO2 was set to 100mM and the concentration of benzyltriethylammonium chloride was set to 1.0mM. The ESR spectrum of the agent was measured in the same manner as in Example 3. As a result, a peak indicating the presence of free radicals appeared, so it was confirmed that methylammonium chloride acted on sodium chlorite (NaClO2) as a free radical generation catalyst to generate chlorine dioxide free radicals.

[0255] [Verification data of Lewis acidity] (1) Measurement conditions As described above, the Lewis acidity of the ammonium salt was measured and calculated by the method described in J. Org. Chem. 2003, 68, 4720-4726. Specifically, as described in J. Org. Chem. 2003, 68, 4720-4726, page 4724, line 21 from the left to page 4724, line 6 from the left, the reaction rate of the oxidation of CoTPP using O2 as a free radical generation source was determined according to page 4725. Figure 6 Lewis acidity ΔE (eV) was calculated from the linear relationship (y=14(ΔE)-8.0) (y is the common logarithm value of the rate constant) provided in the graph.

[0256] (2) Lewis acidity value The values ​​of the Lewis acidity measured and calculated by the method of (1) above are shown below. The values ​​of the Lewis acidity of the four kinds of ammonium in Examples 3 to 7 are shown in Table 16 below. In addition, the values ​​of the Lewis acidity of various other ammoniums are shown in Table 17 below. In addition, the Lewis acidity of pralidoxime iodide (PAM) was measured by the same method except for Tables 16 and 17 below, and the result was 0.60 eV.

[0257]

Table 16

[0258]

Table 17

[0259] (Experimental Example 13) The bactericidal effects were confirmed using the agent of Example 5 containing ammonium chloride, the agent of Example 6 containing benzalkonium chloride, the agent of Example 7 containing benzyltriethylammonium chloride, and the agent of Example 8 containing methylammonium chloride.

[0260] The bactericidal effect was determined in the same manner as in Experimental Example 3 except that an equal amount of an agent containing ammonium chloride and sodium chlorite (Example 5), an agent containing benzalkonium chloride and sodium chlorite (Example 6), or an agent containing benzyltriethylammonium chloride and sodium chlorite (Example 7) was used instead of the agent of Example 3 (the agent containing benzethonium chloride and sodium chlorite). Escherichia coli (Escherichia coli MV1184) was used as the bacterial species. In addition, an aqueous solution containing only ammonium chloride, benzalkonium chloride, benzyltriethylammonium chloride or methylammonium chloride without sodium chlorite (Comparative Example) was used instead of the agent of Example 5, 6, 7 or 8, and the bactericidal effect was determined by the same method.

[0261] (2) Results of determination of bactericidal effect The results of the MIC (minimum inhibitory concentration) measured by the above (1) are shown in the following Table 18

[0262]

Table 18

[0263] As shown in Table 18, when using a drug containing ammonium chloride and sodium chlorite (Example 5), a drug containing benzalkonium chloride and sodium chlorite (Example 6), a drug containing benzyltriethylammonium chloride and sodium chlorite (Example 7), or a drug containing methylammonium chloride and sodium chlorite (Example 8), the bactericidal effect of the drug of the present invention can be confirmed. In contrast, in an aqueous solution containing only ammonium chloride, benzalkonium chloride, benzyltriethylammonium chloride or methylammonium chloride without sodium chlorite, there is no bactericidal effect. It can be confirmed that the chlorine dioxide free radical generated by sodium chlorite through the catalytic action of ammonium chloride, benzalkonium chloride, benzyltriethylammonium chloride or methylammonium chloride has exerted a bactericidal effect.

[0264] (Experimental Example 14: Suppression of symptoms of ulcerative colitis) A pH buffer solution was added to the agent of Example 3 to adjust the pH to 5.35. This agent is hereinafter referred to as "MA-T".

[0265] Next, using a disposable feeding needle (needle diameter (pre-drying needle): 2 mm, tube diameter: 1.18 mm, tube length: 50 mm), C57BL / 6J male mice around 12 weeks old (raised in the animal facility 5-05 of the School of Medicine, Osaka University) were anally administered 150 μl each of MA-T (pH 5.35) or vehicle (water only) 3 days before administration of 2% dextran sulfate sodium aqueous solution (DSS) (MP Biomedicals) and on days 6-8, 10-12, and 14-16 after DSS administration. During this period, 2% DSS was added to the water bottle to allow free drinking. Six days after the start of 2% DSS administration, the mice were replaced with daily water administration (drinking water). Body weight was measured between the 2% DSS drinking period and the subsequent daily water drinking period. The weight loss after DSS administration was analyzed based on the body weight of the mice on the day of the start of 2% DSS administration. Fig. 27 The chart shows the results. Fig. 27 is the male mouse * P<0.05. (t-test) results. The horizontal axis represents the number of days before or after the start of DSS administration, and the vertical axis represents the change in body weight (grams). The ● in the figure represents the excipient administration (drinking water) group, and the ○ represents the MA-T administration group. As shown in the figure, the body weight of the mouse group continued to decrease from the start of 2% DSS administration until the start of MA-T or excipient administration. This suggests that dextran sulfate sodium induced colitis occurred. Thereafter, after the start of 2% DSS administration, if MA-T or excipient administration was started, the body weight in all groups recovered (increased again). This suggests that dextran sulfate sodium induced colitis was suppressed. In addition, the amount of body weight recovery (re-increase) in the MA-T administration group was greater than that in the vehicle administration group. This suggests that dextran sulfate sodium induced colitis was strongly suppressed by MA-T administration compared to excipient administration. That is, through this experimental example, it was confirmed that MA-T has an inhibitory effect on dextran sulfate sodium induced colitis. From this, it can be inferred that MA-T has a bactericidal action (bactericidal effect). This point was further confirmed in Experimental Example 15 described below.

[0266] (Experimental Example 15: Changes in Intestinal Flora) Experimental Example 14( Fig. 27), feces (3 to 5 pieces) of the vehicle-administered group and the MA-T (pH 5.35)-administered group were collected just before DSS administration (on the day of administration start) and 16 days after administration started. After measuring the weight of the feces, RNAlater (RNAlater (ml) = weight of feces (g) × 9) (Invitrogen) was added, and a 10-fold dilution (v / w) of fecal fragments was prepared using a vortex mixer. 200 μl of fecal fragments were transferred to a 2 ml screw-cap microtube, 1 ml of PBS (-) was added, stirred with a vortex mixer, and centrifuged for 5 minutes (4°C, 13,000 × g). The supernatant was removed, 1 ml of PBS (-) was added again, stirred with a vortex mixer, and centrifuged for 5 minutes (4°C, 13,000 × g), and the supernatant was removed. 0.3 g of glass beads (0.1 mm in diameter), 300 μl of Tris-SDS solution (100 mM Tris-HCl, 40 mM EDTA (pH 9.0), 1% SDS), and 500 μl of TE-saturated phenol (nacalai) were added, and the mixture was stirred using FastPrep (5.0 power level, 30 seconds) (MP Biomedicals). After 5 minutes of centrifugation (4°C, 20,000 × g), 400 μl of the supernatant was transferred to a 2 ml screw-cap microtube, and an equal amount of phenol-chloroform-isoamyl alcohol (25:24:1) (nacalai) was added, and the mixture was stirred again using FastPrep (4.0 power level, 45 seconds). After 5 minutes of centrifugation (4°C, 20,000 × g), transfer 250 μl of the supernatant to a 1.5 ml screw-cap microtube, add 25 μl of 3M sodium acetate (pH 5.2) and 300 μl of isopropanol (nacalai), stir with a vortex mixer, and centrifuge for 5 minutes (4°C, 20,000 × g). Remove the supernatant, add 800 μl of 80% ethanol, and centrifuge for 5 minutes (4°C, 20,000 × g). Remove the supernatant, place the tube in a block incubator at 60 degrees and dry for 30 minutes. Add 200 μl of TE (pH 8.0) (nacalai) to dissolve the recovered nucleic acid (DNA). The prepared DNA solution and standard plasmid DNA of intestinal bacteria were used to analyze the number of intestinal bacteria (Blautia cluster, Clostridium coccoides, Bacteroides fragilis) in 1 g of feces by quantitative PCR ((1) 94°C for 5 minutes, (2) 94°C for 20 seconds, (3) 55°C for 20 seconds, (4) 72°C for 50 seconds, (1) 1 cycle / (2) to (4) 45 cycles) (Step One Plus, Applied Biosystems).The primer sets used in the PCR method are shown below. Primer Set: Blautia cluster (Blautella cluster), 5′-gtgaaggaagaagtatctcgg-3′ and 5′-ttggtaaggttcttcgcgtt-3′; Clostridium coccoides ( Clostridium coccum ), 5′-aaatgacgggtacctgactaa-3′ and 5′-ctttgagtttcattcttgcgaa-3′; Bacteroides fragilis (Bacteroides fragilis), 5′-atagcctttcgaaagaagat-3′ and 5′-ccagtatcaactgcaatttta-3′.

[0267] Fig.28 The bar graphs represent the detection counts of the above-mentioned bacteria. In each bar graph, "Day0" represents the day immediately before the administration of DSS (the day the administration starts), and "Day16" represents 16 days after the administration starts. In each bar graph, the bar graph on the left represents the excipient administration group, and the bar graph on the right represents the MA-T administration group. In addition, the vertical axis represents the number of bacteria (Number) per 1 gram (g) of feces. As shown in the figure, it was confirmed that MA-T induced changes in the intestinal flora. That is, it was confirmed that MA-T has a bactericidal effect (bactericidal effect).

[0268] [Examples of agricultural and livestock drugs] Next, specific examples of the agricultural and livestock medicine are described. However, the agricultural and livestock medicine of the present invention is not limited by the following examples. In addition, in the following examples of the present invention, the agricultural and livestock medicine of the examples is sometimes simply referred to as "medicine".

[0269] In the following experimental examples of agricultural and livestock drugs, the drugs of Examples 3 to 4 and Comparative Examples 1 to 8 described above were used as agricultural and livestock drugs.

[0270] (Experimental Example 1 of Agricultural and Livestock Drugs) In Experimental Example 1 of the agricultural and livestock drug, the following bacterial solution was first prepared. Use bacteria: Staphylococcus aureus Escherichia coli MV1184 Bacterial liquid: The bacteria grown in the BHI agar medium were collected with a platinum loop, added to the BHI liquid medium and shaken, and 50 μL of the bacterial solution grown in the BHI liquid medium for one day and night was diluted 190 times with the BHI liquid medium, mixed and stirred to prepare a bacterial solution.

[0271] Using the above bacterial solution, the effect was studied in the following manner.

[0272] Use a UV sterilizing lamp to sterilize the microplate (with a lid) for 10 minutes. Then, use a micropipette to inject the BHI liquid culture medium, bacterial solution and agricultural and livestock drugs involved in Example 3 into each well in turn. After culturing at 37°C for 24 hours, confirm with an ELISA instrument to find the MIC (minimum inhibitory concentration). It should be noted that in the control, only the liquid culture medium was confirmed. In addition, 10 μL of the culture solution was taken out from the well near the MIC, inoculated in a culture dish, and cultured at 37°C for 24 hours to find the MBC (minimum bactericidal concentration). The results are shown in Table 19.

[0273] The MIC and MBC were determined in the same manner using the fungicide of Comparative Example 1 instead of the agricultural and livestock agent of Example 3. The results are shown in Table 19.

[0274] The MIC of Staphylococcus aureus was determined in the same manner using the bactericidal and deodorizing agents of Comparative Examples 2 to 5 instead of the agricultural and livestock agent of Example 3. The results are shown in Table 19.

[0275] The test product according to Comparative Example 6 was used instead of the agricultural and livestock agent according to Example 3, and the MIC of Staphylococcus aureus and the MIC and MBC of Escherichia coli were determined in the same manner. The results are shown in Table 19.

[0276]

Table 19

[0277] (Experimental Example 2 of Agricultural and Livestock Drugs) The MIC of Escherichia coli was determined in the same manner using the agricultural and livestock agent according to Example 4 or Comparative Example 7 or 8 instead of the agricultural and livestock agent according to Example 3. The results are shown in Table 20.

[0278]

Table 20

[0279] (Experimental Example 3 of Agricultural and Livestock Drugs) In Experimental Example 3 of the agricultural and livestock drug, the following bacterial solution was first prepared. Use bacteria: Streptococcus pyogenes Bacterial liquid: The same procedure as in Experimental Example 1 of the agricultural and livestock chemical was carried out to obtain a bacterial liquid.

[0280] The above bacterial solution was used in the same manner as in Experimental Example 1 of the agricultural and livestock chemical, and the MIC and MBC were determined using the agricultural and livestock chemical according to Example 3. The results are shown in Table 21.

[0281]

Table 21

[0282] (Experimental Example 4 of Agricultural and Livestock Drugs) In Experimental Example 4 of the agricultural and livestock drug, the following bacterial solution was first prepared. Use bacteria: Streptococcus mutans Bacterial liquid: The bacteria grown in the BHI agar medium were collected with a platinum loop, added to the BHI liquid medium and shaken, and 50 μL of the bacterial solution grown in the BHI liquid medium for one day and night was diluted 190 times with the BHI liquid medium, mixed and stirred to prepare a bacterial solution.

[0283] Using the above bacterial solution, the effect was studied in the following manner.

[0284] Use a micropipette to inject the bacterial liquid into the BHI liquid culture medium added to two test tubes. Add sucrose in a manner to reach 0.2%. Cultivate at 37°C for 18 hours to form a biofilm. Discard the culture medium in the test tube into a beaker and wash twice with PBS. Inject the agricultural and livestock drugs involved in Example 3 and PBS into each, and shake at 37°C for 30 minutes. Discard the liquid in the test tube into a beaker and wash twice with PBS. Inject BHI liquid culture medium into the test tube and culture at 37°C for 24 hours. Inoculate 10μL of each culture medium into ordinary agar medium and culture at 37°C for 24 hours. Visually confirm the presence or absence of colonies. As a result, no colonies were confirmed in the case of injecting the agricultural and livestock drugs involved in Example 3, but a large number of colonies were confirmed in the case of injecting PBS.

[0285] In order to confirm the effect on the bacteria inside the biofilm, the following confirmation test was further performed.

[0286] Use a micropipette to inject the bacterial liquid into the BHI liquid culture medium added to the microtube for the masher. Add sucrose in a manner to reach 0.2%. Cultivate at 37°C for 18 hours to form a biofilm. Discard the culture medium in the microtube into a beaker and wash twice with PBS. Inject the agricultural and livestock drugs involved in Example 3 and PBS respectively, and culture (cultivate) at 37°C for 15 minutes and 30 minutes. Discard the liquid in the microtube into a beaker and wash twice with PBS. Inject BHI liquid culture medium into the test tube, homogenize, and culture at 37°C for 24 hours. Inoculate 10μL of each culture medium in ordinary agar medium and culture at 37°C for 24 hours. Visually confirm the presence or absence of colonies. As a result, no colonies were confirmed in the case of injecting the agricultural and livestock drugs involved in Example 3, but a large number of colonies were confirmed in the case of injecting PBS. This shows that the agricultural and livestock agent according to Example 3 penetrates into the biofilm and acts inside the biofilm, thereby showing a bactericidal effect.

[0287] (Experimental Example 5 of Agricultural and Livestock Drugs) In Experimental Example 5 of the agricultural and livestock agent, the agricultural and livestock agent according to Example 3 was used in the same manner as in Experimental Example 1 of the agricultural and livestock agent, except that the following bacterial species were used, and the MIC and MBC were determined. The results are shown in Table 22. Use bacteria: Bacteria 1 (Porphyromonas gingivalis) Bacteria 2 (Treponema denticola) Bacteria 3 (Tannerella forsythensis) Bacteria 4 (Aggregatibacter actinomycetemcomitans)

[0288]

Table 22

[0289] (Experimental Example 6 of Agricultural and Livestock Drugs) For iron, aluminum, tinplate and stainless steel, each test piece (25.4 mm × 25.4 mm) was washed, and then immersed in a resin container to which the agricultural and livestock agent involved in Example 3, a 1.2% aqueous solution of sodium hypochlorite and tap water were added, and the resin container was covered. After each time recorded in Tables 23 and 24, the test piece was taken out onto a non-woven fabric and the condition of the test piece was visually confirmed. Confirmation was performed by taking photos as needed, and in addition, observation was performed under a microscope when it was difficult to know the changes. The following criteria were used for evaluation.

[0290] -: No corrosion ±: Rust +: A certain amount of rust ++: Lots of rust +++: Corrosion of metal surface

[0291]

Table 23

[0292]

Table 24

[0293] (Experimental Example 7 of Agricultural and Livestock Drugs) Deodorization performance test was conducted in accordance with the Japan Electrical Manufacturers Association standard JEM1467 "Household air purifier". 3 In an acrylic container (1m long × 1m wide × 1m deep), start the stirrer, burn the cigarettes, and fill the container with smoke. After all the cigarettes are burned, stop the stirrer, start the sprayer, and spray the agricultural and livestock agent involved in Example 3. The concentrations of the three components of ammonia, acetaldehyde and acetic acid in the container are measured at regular intervals for 2 hours, and the concentration changes are tracked. Similarly, formaldehyde vapor is injected into the acrylic container, and the formaldehyde concentration in the container is measured at regular intervals for 2 hours, and the concentration changes are tracked. It should be noted that the sprayer is operated in 'Manual' mode. In addition, as a control, a blank test without operating the sprayer is also carried out. The results are shown in Tables 25 to 28. The determination of the odor components is carried out by a detection tube (manufactured by GASTEC), and the detection tube used is shown below.

[0294] Use test tube Ammonia No.3L Acetaldehyde No.92L Acetic acid No.81L Formaldehyde No.91

[0295]

Table 25

[0296]

Table 26

[0297]

Table 27

[0298]

Table 28

[0299] (Experimental Example 8 of Agricultural and Livestock Drugs) The deodorizing performance of cigarette odor was measured by spraying the agricultural and livestock agent involved in Example 3 using a sprayer. First, a cigarette was burned in a room with a width equivalent to 6 tatami mats, so that the smoke filled the room and reached a certain concentration. Next, the sprayer was configured, and the odor intensity in the room was measured three times: before starting, 1 hour after starting, and 2 hours after starting. The sprayer was configured next to the wall of the room, and the odor was collected at a height of 1m in the center of the room. Two stirring fans were set in the room and set to a continuous stirring state. It should be noted that the sprayer was operated in 'Manual' mode. In addition, as a control, a blank test without operating the sprayer was also carried out. The odor intensity was determined in the following manner using the 6-level odor intensity representation method. The results are shown in Table 29.

[0300] The testers (group) who evaluated the odor intensity were set to 6, and the results were calculated by averaging the intensity values ​​of each person. The 6-level odor intensity expression is a method of numerically expressing the intensity of odors using human sense of smell. The group that conducted this test was people who had undergone a legally required olfactory test and were certified to have a normal sense of smell.

[0301] The following numerical values ​​are used as reference in the six-level odor intensity representation system. 0: No odor 1: Very weak odor (detection threshold concentration) 2: Weak odor (perception threshold concentration) 3: Easily detectable odor 4: Strong odor 5: Very strong odor

[0302]

Table 29

[0303] (Experimental Example 9 of Agricultural and Livestock Drugs) The agricultural and livestock agent involved in Example 3 was sprayed using a sprayer, and the removal performance of airborne bacteria (general bacteria and fungi) was measured. First, a sprayer was placed in a room with a width equivalent to 6 tatami mats, and the concentration of airborne bacteria in the air was measured three times: before startup, 1 hour after startup, and 2 hours after startup. The sprayer was placed next to the wall of the room, and the collection of airborne bacteria was set at a height of 1m in the center of the room. Two stirring fans were set in the room and set to a continuous stirring state. The determination of airborne bacteria was carried out by the filtration capture method using a membrane filter. It should be noted that the sprayer was operated in 'Manual' mode. In addition, as a control, a blank test without starting the sprayer was carried out. The results are shown in Tables 30 and 31.

[0304] Measurement conditions and the like of Experimental Example 9 of agricultural and livestock drugs Filter used: Made by Toyo Filter Paper Co., Ltd., 37mm monitor Air suction volume: 300L (20L per minute for 15 minutes) Medium used: m-TGE Broth liquid medium for general bacteria (manufactured by Toyo Seisakusho) m-Green Y&M Broth liquid culture medium for fungi (manufactured by Toyo Seisakusho) Culture conditions: general bacteria 30℃ 72 hours Fungus 30℃ 5 days

[0305]

Table 30

[0306]

Table 31

[0307] (Experimental Example 10 of Agricultural and Livestock Drugs) In Experimental Example 10 of the agricultural and livestock agent, the MIC or MBC was determined in the same manner as in Experimental Example 1 of the agricultural and livestock agent except that the following bacterial species were used and the agricultural and livestock agent according to Example 3 was used. The results are shown in Table 32. Use bacteria: Streptococcus mutans Hemolytic Streptococcus Bacillus subtilis Methicillin-resistant Staphylococcus aureus (MRSA)

[0308]

Table 32

[0309] (Experimental Example 11 of Agricultural and Livestock Drugs) According to the instrumental analysis implementation manual; detector tube method, gas chromatography ((Company) Fiber Evaluation Technology Council Deodorant Processed Fiber Product Certification Standards Approved), a deodorization test was conducted using the agricultural and livestock agent involved in Example 3. The results are shown in Table 33.

[0310]

Table 33

[0311] (Experimental Example 12 of Agricultural and Livestock Drugs) By administering the agricultural and livestock drug of the present invention to mice, it was confirmed that the agricultural and livestock drug of the present invention has high safety.

[0312] Using the agricultural and livestock medicine of Example 3, an acute oral toxicity test was conducted on mice based on the OECD TG420 acute oral toxicity test (fixed dose method). It should be noted that the above test was conducted by the Japan Food Analysis Center. As a result, the LD50 value of the above agricultural and livestock medicine was 2000 mg / kg or more regardless of male and female. Therefore, it can be seen that the agricultural and livestock medicine of the present invention is very safe.

[0313] (Experimental Example 13 of Agricultural and Livestock Drugs) By administering the agricultural and livestock drug of the present invention to rabbits, it was confirmed that the agricultural and livestock drug of the present invention has high safety.

[0314] Using the agricultural and livestock medicine of Example 3, an eye irritation test was conducted on rabbits based on OECD TG405 acute eye irritation / corrosion. It should be noted that the above test was conducted by the Japan Food Analysis Center. As a result, it can be seen that the irritation of the agricultural and livestock medicine is non-irritating. Therefore, it can be seen that the agricultural and livestock medicine of the present invention is extremely safe.

[0315] (Experimental Example 14 of Agricultural and Livestock Drugs) By administering the agricultural and livestock drug of the present invention to rabbits, it was confirmed that the agricultural and livestock drug of the present invention has high safety.

[0316] The agricultural and livestock medicine of Example 3 was subjected to a primary skin irritation test on rabbits based on OECD TG404 acute skin irritation / corrosion. It should be noted that the above test was conducted by the Japan Food Analysis Center. As a result, it can be seen that the irritation of the agricultural and livestock medicine is a weak irritant. Therefore, it can be seen that the agricultural and livestock medicine of the present invention is very safe.

[0317] (Experimental Example 15 of Agricultural and Livestock Drugs) By administering the agricultural and livestock drug of the present invention to guinea pigs, it was confirmed that the agricultural and livestock drug of the present invention has high safety.

[0318] Using the agricultural and livestock medicine of Example 3, a continuous skin irritation test was conducted by applying the agricultural and livestock medicine to guinea pigs for 14 consecutive days. It should be noted that the above test was conducted by Life Science Research Institute Co., Ltd. As a result, it can be seen that the irritation of the agricultural and livestock medicine is non-irritating. Therefore, it can be seen that the agricultural and livestock medicine of the present invention is very safe.

[0319] (Experimental Example 16 of Agricultural and Livestock Drugs) By administering the agricultural and livestock drug of the present invention to guinea pigs, it was confirmed that the agricultural and livestock drug of the present invention has high safety.

[0320] Using the agricultural and livestock medicine of Example 3, a skin sensitivity test was conducted on guinea pigs by the maximization test method. It should be noted that the above test was conducted by Life Science Research Institute Co., Ltd. As a result, it can be seen that the irritation of the agricultural and livestock medicine does not cause skin sensitivity. Therefore, it can be seen that the agricultural and livestock medicine of the present invention is very safe.

[0321] (Experimental Example 17 of Agricultural and Livestock Drugs) By administering the agricultural and livestock drug of the present invention to humans, it was confirmed that the agricultural and livestock drug of the present invention has high safety.

[0322] By using the agricultural and livestock medicine of Example 3, a patch having absorbed the agricultural and livestock medicine was attached to a human body for 24 hours, thereby conducting a human patch test. It should be noted that the above test was conducted by the Life Science Research Institute Co., Ltd. As a result, it can be seen that the irritation of the agricultural and livestock medicine is non-irritating. Therefore, it can be seen that the agricultural and livestock medicine of the present invention is very safe.

[0323] (Experimental Example 18 of Agricultural and Livestock Drugs) It has been confirmed that the agricultural and livestock agent of the present invention can suppress the occurrence of rice blast.

[0324] Use salt water to select Koshihikari rice seeds, remove floating rice seeds, and thus remove diseased seeds. Then wash the obtained rice seeds with water, drain the water, and put them into a coarse mesh salon bag. Next, prepare a dilution solution (hereinafter also referred to as "200 times solution") of the agricultural and livestock agent of Example 3 above. Next, immerse the rice seeds in the above salon bag in a 200 times solution that is 2 times the weight of the rice seeds for 24 hours. During the above immersion treatment, the water is not changed. After the above immersion, the rice seeds are air-dried, and the rice seeds are immersed again for 6 days. During the above immersion treatment, the water is not changed. Furthermore, the rice seeds after the above immersion treatment are immersed again for 6 days.

[0325] Next, the rice seeds were sown in a seedling raising box, and each seedling raising box was sprayed with 500 mL of the 200-fold solution before raising the seedlings. The obtained seedlings were planted in a rice field and cultivated by conventional methods. In addition, the occurrence of rice blast was confirmed during the cultivation. The control group used rice seeds of "Love at First Sight (ひとめぼれ)" instead of the Koshihikari rice, and was not immersed in the 200-fold solution. The seeds were transplanted to a rice field adjacent to the rice field where the Koshihikari rice was planted. In addition, the same method was used to confirm the occurrence of rice blast.

[0326] As a result, in the rice field treated with the 200-fold dilution, no rice blast was observed. In contrast, rice blast was observed in the control group. From the above results, it can be seen that the agricultural and livestock agent of the present invention can suppress the occurrence of rice blast.

[0327] (Experimental Example 19 of Agricultural and Livestock Drugs) It was confirmed that the agricultural and livestock agent of the present invention can suppress the spread of rice blast.

[0328] When plowing a rice field where rice blast is prevalent, 10 L of a dilution (hereinafter also referred to as "10-fold solution") obtained by diluting the agricultural and livestock agent of Example 3 to 10 times is added to each of the rice fields 10a, and the plowing is performed. Next, the seedlings of the Koshihikari rice of Experimental Example 18 of the agricultural and livestock agent are transplanted into the rice field after the plowing and cultivated. Next, when the occurrence of rice blast is confirmed during the cultivation, the rice blast diseased plants are removed, and 1 L of the 10-fold solution is sprayed around the cultivated rice blast diseased plants in each of the rice fields 10a. The control group uses the seedlings of the control group of Experimental Example 18 of the agricultural and livestock agent instead of the seedlings of the Koshihikari rice of Experimental Example 18 of the agricultural and livestock agent, and neither the 10-fold solution is added nor sprayed in the above field, and is transplanted into a rice field adjacent to the rice field planted with the above Koshihikari rice, and the cultivation is performed in the same manner except that the seedlings are transplanted into a rice field adjacent to the rice field planted with the above Koshihikari rice. Furthermore, it was confirmed whether the rice blast disease occurred in the rice field where the control group was planted in the above cultivation spread to the rice field where the above Koshihikari rice seedlings were planted.

[0329] As a result, the occurrence and spread of rice blast were observed in the rice field planted with the control group. In contrast, in the rice field planted with the Koshihikari rice seedlings, slight rice blast was observed in the upper part of the primary stem about 2 to 3 m away from the rice field planted with the control group, but the spread of rice blast to other parts of the rice field was not observed. From this result, it can be seen that the agricultural and livestock agent of the present invention can inhibit the spread of rice blast.

[0330] (Experimental Example 20 of Agricultural and Livestock Drugs) It was confirmed that the agricultural and livestock agent of the present invention can repel stink bugs or pests.

[0331] In the same manner as in Experimental Example 19 of the agricultural and livestock pesticide, one paddy field owned by 23 farmers was treated, except that the Koshihikari rice seedlings of Experimental Example 18 of the agricultural and livestock pesticide were planted in the paddy field and cultivated. After the cultivation, each farmer was asked about the extent to which stink bugs or pests approached the paddy field compared with previous years.

[0332] As a result, 8 farmers responded that they observed the repelling of stink bugs or pests. This shows that the agricultural and livestock pesticide of the present invention can repel stink bugs or pests.

[0333] [Examples of amino acids, peptides and phospholipids] Hereinafter, examples of amino acids, peptides, and phospholipids will be described.

[0334] [Reference Example 6] By the above-mentioned "Lewis acidity determination method (2)", the reaction rate constants of various amino acids, peptides and phospholipids are determined as follows. It should be noted that in the following table, "L-aspartate" represents L-aspartic acid, "L-glutamate" represents L-glutamic acid, "L-glycine" represents L-glycine, "L-lysine" represents L-lysine, "L-arginine" represents L-arginine, "GSSG" represents oxidized glutathione, "Cys-Cys" represents cystine, "DPPS" represents dipalmitoylphosphatidylserine, "DPPC" represents dipalmitoylphosphatidylcholine, and "adenine" represents adenine. In addition, "K obs ” represents the reaction rate constant (k cat As shown in the following table, all amino acids, peptides and phospholipids were confirmed to show Lewis acidity.

[0335]

Table tpp2

[0336] [Reference Example 7] The Lewis acidity of each of phosphatidylserine, phosphatidylcholine, phosphatidic acid, phosphatidylethanolamine, phosphatidylglycerol, cardiolipin, L-aspartic acid, and L-serine was measured by the "Lewis acidity measurement method (1)" or the "Lewis acidity measurement method (2)". As a result, the Lewis acidity of phosphatidylserine, phosphatidylcholine, and L-aspartic acid was confirmed by both the "Lewis acidity measurement method (1)" and the "Lewis acidity measurement method (2)". The Lewis acidity of phosphatidic acid was confirmed by the "Lewis acidity measurement method (2)". The Lewis acidity of cardiolipin was confirmed by the "Lewis acidity measurement method (1)". Furthermore, the Lewis acidity of ganglioside GM1 and sphingomyelin, which are sphingomyelins (phospholipids), was confirmed by the "Lewis acidity measurement method (2)".

[0337] [Example 9] Chlorine dioxide radicals were produced from chlorous acid or its salt (sodium chlorite) using various amino acids, peptides and phospholipids whose Lewis acidity was measured in Reference Examples 6 and 7. Thus, it was confirmed that the various amino acids, peptides and phospholipids acted as chlorine dioxide radical generation catalysts on chlorous acid or its salt (sodium chlorite).

[0338] [Example 10] The above-mentioned various ammoniums were used in the same manner as in Examples 3 to 8 to prepare the agents. In addition, the above-mentioned various ammoniums were replaced with various amino acids, peptides and phospholipids whose Lewis acids were measured in Reference Examples 6 and 7, and the agents were prepared in the same manner as in Examples 3 to 8. The above-mentioned agents were tested in the same manner as in the experimental examples and the above-mentioned agricultural and livestock agents, and the agents were used to confirm the bactericidal effect.

[0339] The preparation of the above-mentioned agent is carried out in the following manner. First, sodium chlorite is dissolved in purified water to obtain a sodium chlorite aqueous solution (liquid A). On the other hand, each of the above-mentioned ammonium, amino acid, peptide and phospholipid is dissolved in purified water to obtain an aqueous solution (liquid B). Further, a solution A with a concentration of 1mM and a solution B with a concentration of 0.2mM are mixed, or a solution A with a concentration of 5mM and a solution B with a concentration of 1mM are mixed, and further diluted to prepare the agent. The concentration of each of the above-mentioned ammonium, amino acid, peptide or phospholipid in the above-mentioned agent is 12.5 to 20ppm. In addition, the concentration of sodium chlorite in the above-mentioned agent is about 0.14mM to 0.22mM.

[0340] Use bacteria: Escherichia coli MV1184 Bacterial liquid: The bacteria grown in the BHI agar medium were collected with a platinum loop, added to the BHI liquid medium and shaken, and 50 μL of the bacterial solution grown in the BHI liquid medium for one day and night was diluted 190 times with the BHI liquid medium, mixed and stirred to prepare a bacterial solution.

[0341] Using the above bacterial solution, the effect (bactericidal action) was examined in the following manner.

[0342] Use a UV sterilization lamp to sterilize the microplate (with a lid) for 10 minutes. Then, use a micropipette to inject BHI liquid culture medium, the above-mentioned bacterial solution, and the above-mentioned drug into each well in turn. After culturing at 37°C for 24 hours, confirm with an enzyme reader and find the MIC (minimum inhibitory concentration). It should be noted that the control group only confirmed the liquid culture medium. In addition, 10μL of the culture solution was taken out from the well near the MIC, inoculated in a culture dish, and cultured at 37°C for 24 hours to find the MBC (minimum bactericidal concentration). Furthermore, as a control group, only A solution (an aqueous solution containing only sodium chlorite: sodium chlorite concentration 40ppm, about 0.44mM) or only B solution (an aqueous solution containing only the above-mentioned ammonium, amino acids, peptides or phospholipids) was used instead of the above-mentioned drug, and the same method was used to study the effect (bactericidal effect).

[0343] According to the results of the bactericidal study conducted in the above manner, methylammonium chloride, ammonium chloride, tetrabutylammonium chloride, benzethonium chloride and benzalkonium chloride as ammonium; glycine, L-serine, L-aspartic acid and proline as amino acids; oxidized glutathione as peptide; and choline as phospholipid were each confirmed to have a bactericidal action (bactericidal effect).

[0344] On the other hand, when only solution A or only solution B is used, there is no bactericidal action (bactericidal effect). That is, when only sodium chlorite or only the above-mentioned ammonium, amino acid, peptide or phospholipid is contained, no bactericidal action is shown, but when both are present, it is presumed that the above-mentioned ammonium, amino acid, peptide or phospholipid acts on sodium chlorite to generate chlorine dioxide radicals, and the chlorine dioxide radicals show bactericidal action.

[0345] Although the present invention has been described above with reference to the embodiments and examples, the present invention is not limited to the above-described embodiments and examples. Various changes that can be understood by those skilled in the art can be made to the configuration and details of the present invention within the scope of the present invention. Possibility of industrial application

[0346] As shown in the above description, according to the manufacture method of free radical generation catalyst of the present invention and free radical, can produce (manufacture) free radical under mild condition.As the purposes of the manufacture method of free radical generation catalyst of the present invention and free radical, for example, can be used for the manufacture method of above-mentioned oxidation reaction product of the present invention.The manufacture method of oxidation reaction product of the present invention can be applied to the oxidation reaction of various oxides that comprise organic compound and inorganic substance, and its application range is wide.In addition, the purposes of free radical generation catalyst of the present invention and the manufacture method of free radical are not limited to the manufacture method of above-mentioned oxidation reaction product of the present invention, can be used for a wide range of purposes.

[0347] In addition, according to the present invention, a medicament and an agricultural and livestock medicament with high safety and high bactericidal effect can be provided. The use of the medicament and agricultural and livestock medicament of the present invention is not particularly limited, and can be used for a wide range of purposes. The medicament and agricultural and livestock medicament of the present invention are very useful, for example, in the agricultural field, the livestock industry field, etc.

[0348] Item 1. A free radical generating catalyst, characterized in that it contains at least one selected from amino acids, proteins, peptides, phospholipids and salts thereof. Item 2. The free radical generating catalyst according to Item 1, wherein the free radical generating catalyst further comprises ammonium. Item 3. The free radical generating catalyst according to Item 2, wherein the ammonium is an ammonium salt represented by the following chemical formula (XI): In the chemical formula (XI), R 11 , R 21 , R 31 and R 41 Each is a hydrogen atom or an aromatic ring, or an alkyl group, the alkyl group may contain an ether bond, a carbonyl group, an ester bond or an amide bond, or an aromatic ring, R 11 , R 21 , R 31 and R 41 They can be the same or different. Or, R 11 , R 21 , R 31 and R 41 Two or more of them can be integrated and bonded to N + Together they form a ring structure, which may be a saturated ring structure or an unsaturated ring structure, may be an aromatic ring or a non-aromatic ring, and may have one or more substituents or may not have one or more substituents; X - It is an anion, which does not include the peroxodisulfate ion. Item 4. The free radical generating catalyst according to Item 3, wherein the ammonium salt represented by the chemical formula (XI) is an ammonium salt represented by the following chemical formula (XII), In the chemical formula (XII), R 111 is an alkyl group having 5 to 40 carbon atoms, which may contain an ether bond, a keto (carbonyl) group, an ester bond or an amide bond, a substituent group, or an aromatic ring; R 21 and X - The same as the chemical formula (XI). Item 5. The free radical generating catalyst according to Item 4, wherein the ammonium salt represented by the chemical formula (XII) is an ammonium salt represented by the following chemical formula (XIII), In the chemical formula (XIII), R 111 and X - The same as the chemical formula (XII). Item 6. The free radical generating catalyst according to Item 4, wherein the ammonium is at least one selected from benzethonium chloride, benzalkonium chloride, cetyltrimethylammonium chloride, tetramethylammonium chloride, ammonium chloride, methylammonium chloride, tetrabutylammonium chloride, cetylpyridinium chloride, cetyltrimethylammonium bromide, dequalinium chloride, edrophonium chloride, didecyldimethylammonium chloride, benzyltriethylammonium chloride, oxitropium bromide, carbachol, glycopyrrolate, safranin, sinapinic acid, tetraethylammonium bromide, cetyltrimethylammonium bromide, succinylcholine, sphingomyelin, ganglioside GM1, denatonium, trigonelline, neostigmine, paraquat, pyridostigmine, phellodendron, pralidoxime iodide, betaine, betaine, carbamylcholine, betaine, lecithin, adenine, guanine, cytosine, thymine, uracil and choline. Item 7. The free radical generating catalyst according to Item 4, wherein the ammonium salt represented by the chemical formula (XII) is benzethonium chloride. Item 8. The free radical generating catalyst according to Item 3, wherein the ammonium salt represented by the chemical formula (XI) is an ammonium salt represented by the following chemical formula (XIV), In the chemical formula (XIV), R 100 A cyclic structure may be formed, and the cyclic structure may be a saturated cyclic structure or an unsaturated cyclic structure, may be an aromatic ring or a non-aromatic ring, and may have one or more substituents or may not have one or more substituents; R 11 and X- The same as the chemical formula (XI). Item 9. The free radical generating catalyst according to Item 3, wherein the ammonium salt represented by the chemical formula (XI) is an ammonium salt represented by the following chemical formula (XV), In the chemical formula (XV), Each Z is CH or N, and may be the same or different. In the case of CH, H may be substituted by a substituent; R 11 and X - The same as the chemical formula (XI). Item 10. The free radical generating catalyst according to Item 3, wherein the ammonium salt represented by the chemical formula (XI) is an ammonium salt represented by the following chemical formula (XVI), In the chemical formula (XVI), R 101 , R 102 , R 103 and R 104 are each a hydrogen atom or a substituent, R 101 , R 102 , R 103 and R 104 They can be the same or different. Or, R 101 , R 102 , R 103 and R 104 Two or more of them can be integrated and bonded to N + Together they form a ring structure, which may be a saturated ring structure or an unsaturated ring structure, may be an aromatic ring or a non-aromatic ring, and may have one or more substituents or may not have one or more substituents; Z is CH or N. In the case of CH, H may be substituted by a substituent; R 11 and X - The same as the chemical formula (XI). Item 11. The free radical generating catalyst according to Item 3, wherein the ammonium salt represented by the chemical formula (XI) is an ammonium salt represented by the following chemical formula (XVII), In the chemical formula (XVII), R 111 ~R 118 are each a hydrogen atom or a substituent, R 111 ~R 118They can be the same or different. Or, R 111 ~R 118 Two or more of them may be integrated to form a cyclic structure, and the cyclic structure may be an aromatic ring or a non-aromatic ring, and may or may not have one or more substituents; Z is CH or N. In the case of CH, H may be substituted by a substituent; R 11 and X - The same as the chemical formula (XI). Item 12. A free radical generating catalyst according to any one of Items 1 to 11, wherein the amino acid is at least one selected from glycine, alanine, valine, leucine, isoleucine, serine, threonine, aspartic acid, glutamic acid, asparagine, glutamine, lysine, hydroxylysine, arginine, cysteine, cystine, methionine, phenylalanine, tyrosine, tryptophan, histidine, proline and 4-hydroxyproline. Item 13. The free radical generating catalyst according to any one of Items 1 to 12, wherein the peptide is at least one of oxidized glutathione (GSSG) and reduced glutathione (GSH). Item 14. The free radical generating catalyst according to any one of Items 1 to 13, wherein the phospholipid is at least one selected from phosphatidylserine, phosphatidylcholine, phosphatidic acid, phosphatidylethanolamine, phosphatidylglycerol, and cardiolipin. Item 15. The radical generating catalyst according to any one of Items 1 to 14, wherein the radical generating catalyst has a Lewis acidity of 0.4 eV or more. Item 16. The free radical generating catalyst according to any one of Items 1 to 15, wherein the free radical generating catalyst has an acid dissociation constant pK as a Bronsted acid of a 5 or more. Item 17. The radical generating catalyst according to any one of Items 1 to 16, which catalyzes the generation of radicals from a radical generating source in a non-acidic reaction system. Item 18. The radical generating catalyst according to any one of Items 1 to 16, which catalyzes the generation of radicals from a radical generating source in an acidic reaction system. Item 19. The radical generating catalyst according to any one of Items 1 to 18, which catalyzes the generation of radicals from a radical generating source in a liquid. Item 20. The free radical generating catalyst according to any one of Items 1 to 19, which catalyzes the generation of free radicals from a free radical generating source in a living body. Item 21. The free radical generating catalyst according to any one of Items 1 to 20, which catalyzes the generation of free radicals from a free radical generating source in a digestive organ. Item 22. The free radical generating catalyst according to Item 22, wherein the digestive organ is at least one selected from the group consisting of the oral cavity, pharynx, esophagus, stomach, duodenum, small intestine, and large intestine. Item 23. The free radical generating catalyst according to Item 21, wherein the digestive organ is the large intestine. Item 24. The radical generating catalyst according to any one of Items 1 to 23, wherein the radical generating source comprises an oxygen-containing acid. Item 25. A free radical generating catalyst according to Item 24, wherein the oxygen-containing acid is at least one selected from boric acid, carbonic acid, orthocarbonic acid, carboxylic acid, silicic acid, nitrous acid, nitric acid, phosphorous acid, phosphoric acid, arsenic acid, sulfurous acid, sulfuric acid, sulfonic acid, sulfinic acid, chromic acid, dichromic acid, permanganic acid and halogen oxygen-containing acid. Item 26. A free radical generating catalyst according to Item 21, wherein the halogen oxygen-containing acid is at least one selected from hypochlorous acid, chlorous acid, chloric acid, perchloric acid, hypobromous acid, bromous acid, bromic acid, perbromic acid, hypoiodous acid, iodous acid, iodic acid and periodic acid. Item 27. The free radical generating catalyst according to any one of Items 1 to 23, wherein the free radical generating source comprises at least one selected from the group consisting of halogen ions, hypohalite ions, halogenate ions, halide ions, and perhalide ions. Item 28. The free radical generating catalyst according to Item 24, wherein the oxygen-containing acid is a halogen oxygen-containing acid or a salt thereof. Item 29. The free radical generating catalyst according to Item 28, wherein the halogen oxygen-containing acid is a chlorine oxygen-containing acid. Item 30. The free radical generating catalyst according to any one of Items 1 to 19, wherein the free radical generating source comprises a chlorite ion. Item 31. The radical generating catalyst according to any one of Items 1 to 26, wherein the radical generating source comprises an electron donor·acceptor linked molecule. Item 32. The free radical generating catalyst according to Item 31, wherein the electron donor-acceptor linked molecule is a nitrogen-containing aromatic cation derivative represented by any one of the following formulas (A-1) to (A-8), a 9-substituted acridine represented by the following formula (A-9) ion, quinoline represented by the following formula (I) ionic derivatives, their stereoisomers and tautomers, and at least one of their salts, In the formulas (A-1) to (A-8) and (A-9), R is a hydrogen atom or any substituent; Ar is the electron donating group, which may be one or more, and in the case of multiple electron donating groups, they may be the same or different; The nitrogen-containing aromatic ring forming the nitrogen-containing aromatic cation may have one or more arbitrary substituents other than R and Ar, or may not have one or more arbitrary substituents other than R and Ar; In the formula (I), R 1 is a hydrogen atom or any substituent; Ar 1 ~Ar 3 Each is a hydrogen atom or the electron-donating group, which may be the same or different, Ar 1 ~Ar 3 At least one of them is the electron donating group. Item 33. The free radical generating catalyst according to Item 32, wherein the electron donor-acceptor linked molecule is 9- 10-Methylacridine ion, Item 34. A free radical generating catalyst, characterized in that it comprises an ammonium salt represented by the following chemical formula (XI), which does not include peroxydisulfate, and the Lewis acidity of the ammonium salt is greater than 0.4 eV; In non-acidic liquids, catalyzes the generation of free radicals from free radical generating sources; The free radical generating source is at least one selected from halous acid, halite ion and halite salt, In the chemical formula (XI), R 11 , R 21 , R 31 and R 41 Each is a hydrogen atom or an aromatic ring, or an alkyl group, the alkyl group may contain an ether bond, a carbonyl group, an ester bond or an amide bond, or an aromatic ring, R 11 , R 21 , R 31 and R 41 They can be the same or different. Or, R 11 , R 21 , R 31 and R 41 Two or more of them can be integrated and bonded to N+ Together they form a ring structure, which may be a saturated ring structure or an unsaturated ring structure, may be an aromatic ring or a non-aromatic ring, and may have one or more substituents or may not have one or more substituents; X - It is an anion, which does not include the peroxodisulfate ion. Item 35. The free radical generating catalyst according to Item 34, wherein In the ammonium salt represented by the chemical formula (XI), R 11 , R 21 , R 31 and R 41 are each a hydrogen atom or an alkyl group, R 11 , R 21 , R 31 and R 41 Each may be the same or different. Item 36. The radical generating catalyst according to Item 35, wherein the alkyl group is an alkyl group having 1 to 40 carbon atoms. Item 37. The radical generating catalyst according to Item 35, wherein the alkyl group is an alkyl group having 1 to 6 carbon atoms. Item 38. The free radical generating catalyst according to any one of Items 34 to 37, wherein the ammonium salt represented by the chemical formula (XI) is an ammonium salt represented by the following chemical formula (XII), In the chemical formula (XII), R 111 is an alkyl group having 5 to 40 carbon atoms, which may contain an ether bond, a carbonyl group, an ester bond or an amide bond, or an aromatic ring; R 21 and X - The same as the chemical formula (XI). Item 39. A free radical generating catalyst according to Item 34, wherein the ammonium salt represented by the chemical formula (XI) is at least one selected from benzethonium chloride, benzalkonium chloride, hexadecyltrimethylammonium chloride, tetramethylammonium chloride, ammonium chloride, methylammonium chloride, tetrabutylammonium chloride, hexadecylpyridinium chloride, hexadecyltrimethylammonium bromide, dequalinium chloride, edrophonium chloride, didecyldimethylammonium chloride, benzyltriethylammonium chloride, oxitropium bromide, carbachol, glycopyrrolate, safranin, sinapinic acid, tetraethylammonium bromide, hexadecyltrimethylammonium bromide, succinylcholine, sphingomyelin, ganglioside GM1, denatonium, fenugreek alkaloids, neostigmine, paraquat, pyridostigmine, phellodendron, pralidoxime iodide, betaine, betaine, carbachol, lecithin and choline. Item 40. The free radical generating catalyst according to Item 34, wherein the ammonium salt represented by the chemical formula (XI) is an ammonium salt represented by the following chemical formula (XIII), In the chemical formula (XIII), R 111 is an alkyl group having 5 to 40 carbon atoms, X - The same as the chemical formula (XI). Item 41. The free radical generating catalyst according to any one of Items 34 to 40, wherein the ammonium salt is benzethonium chloride. Item 42. The free radical generating catalyst according to Item 34, wherein the ammonium salt represented by the chemical formula (XI) is an ammonium salt represented by the following chemical formula (XIV), In the chemical formula (XIV), R 100 A cyclic structure may be formed, and the cyclic structure may be a saturated cyclic structure or an unsaturated cyclic structure, may be an aromatic ring or a non-aromatic ring, and may have one or more substituents or may not have one or more substituents; R 11 and X - The same as the chemical formula (XI). Item 43. The free radical generating catalyst according to Item 34, wherein the ammonium salt represented by the chemical formula (XI) is an ammonium salt represented by the following chemical formula (XV), In the chemical formula (XV), Each Z is CH or N, and may be the same or different. In the case of CH, H may be substituted by a substituent; R 11 and X - The same as the chemical formula (XI). Item 44. The free radical generating catalyst according to Item 34, wherein the ammonium salt represented by the chemical formula (XI) is an ammonium salt represented by the following chemical formula (XVI), In the chemical formula (XVI), R 101 , R 102 , R 103 and R 104 are each a hydrogen atom or a substituent, R 101 , R 102 , R 103 and R 104They can be the same or different. Or, R 101 , R 102 , R 103 and R 104 Two or more of them can be integrated and bonded to N + Together they form a ring structure, which may be a saturated ring structure or an unsaturated ring structure, may be an aromatic ring or a non-aromatic ring, may have one or more substituents or may not have one or more substituents; Z is CH or N. In the case of CH, H may be substituted by a substituent; R 11 and X - The same as the chemical formula (XI). Item 45. The free radical generating catalyst according to Item 34, wherein the ammonium salt represented by the chemical formula (XI) is an ammonium salt represented by the following chemical formula (XVII), In the chemical formula (XVII), R 111 ~R 118 are each a hydrogen atom or a substituent, R 111 ~R 118 They can be the same or different. Or, R 111 ~R 118 Two or more of them may be integrated to form a cyclic structure, and the cyclic structure may be an aromatic ring or a non-aromatic ring, and may or may not have one or more substituents; Z is CH or N. In the case of CH, H may be substituted by a substituent; R 11 and X - The same as the chemical formula (XI). Item 46. A free radical generating catalyst according to Item 34, wherein the ammonium salt is NH4 + of salt. Item 47. A free radical generating catalyst according to Item 46, wherein the ammonium salt is NH4Cl. Item 48. The free radical generating catalyst according to any one of Items 34 to 38, 40 and 42 to 46, wherein the ammonium salt is a hexafluorophosphate salt of the ammonium. Item 49. The radical generating catalyst according to any one of Items 34 to 48, wherein the halous acid is at least one selected from chlorous acid, bromous acid, and iodous acid. Item 50. The free radical generating catalyst according to any one of Items 34 to 48, wherein the free radical generating source is a chlorite ion. Item 51. A free radical generating catalyst, characterized in that it comprises an ammonium salt represented by the following chemical formula (XI), and the Lewis acidity of the ammonium salt is greater than 0.4 eV; catalyzing the generation of free radicals from a free radical generating source in the presence of an oxidizing agent; The oxidant is O2; The free radical generating source is a nitrogen-containing aromatic cation derivative represented by any one of the following formulas (A-1) to (A-8), a 9-substituted acridine represented by the following formula (A-9): ion, quinoline represented by the following formula (I) ionic derivatives, their stereoisomers and tautomers, and at least one of their salts, In the chemical formula (XI), R 11 , R 21 , R 31 and R 41 Each is a hydrogen atom or an aromatic ring, or an alkyl group, the alkyl group may contain an ether bond, a carbonyl group, an ester bond or an amide bond, or an aromatic ring, R 11 , R 21 , R 31 and R 41 They can be the same or different. Or, R 11 , R 21 , R 31 and R 41 Two or more of them can be integrated and bonded to N + Together they form a ring structure, which may be a saturated ring structure or an unsaturated ring structure, may be an aromatic ring or a non-aromatic ring, and may have one or more substituents or may not have one or more substituents; X - It is an anion; In the formulas (A-1) to (A-8) and (A-9), R is a hydrogen atom or any substituent; Ar is the electron donating group, which may be one or more, and in the case of multiple electron donating groups, they may be the same or different; The nitrogen-containing aromatic ring forming the nitrogen-containing aromatic cation may have one or more arbitrary substituents other than R and Ar, or may not have one or more arbitrary substituents other than R and Ar; In the formula (I), R 1 is a hydrogen atom or any substituent; Ar 1 ~Ar 3 Each is a hydrogen atom or the electron-donating group, which may be the same or different, Ar 1 ~Ar 3 At least one of them is the electron donating group. Item 52. The free radical generating catalyst according to Item 51, wherein In the ammonium salt represented by the chemical formula (XI), R 11 , R 21 , R 31 and R 41 are each a hydrogen atom or an alkyl group, R 11 , R 21 , R 31 and R 41 Each may be the same or different. Item 53. The radical generating catalyst according to Item 52, wherein the alkyl group is an alkyl group having 1 to 40 carbon atoms. Item 54. The radical generating catalyst according to Item 52, wherein the alkyl group is an alkyl group having 1 to 6 carbon atoms. Item 55. The free radical generating catalyst according to any one of Items 51 to 54, wherein the ammonium salt represented by the chemical formula (XI) is an ammonium salt represented by the following chemical formula (XII), In the chemical formula (XII), R 111 is an alkyl group having 5 to 40 carbon atoms, which may contain an ether bond, a carbonyl group, an ester bond or an amide bond, or an aromatic ring; R 21 and X - The same as the chemical formula (XI). Item 56. A free radical generating catalyst according to Item 51, wherein the ammonium salt is at least one selected from benzethonium chloride, benzalkonium chloride, cetyltrimethylammonium chloride, tetramethylammonium chloride, ammonium chloride, methylammonium chloride, tetrabutylammonium chloride, cetylpyridinium chloride, cetyltrimethylammonium bromide, dequalinium chloride, edrophonium chloride, didecyldimethylammonium chloride, benzyltriethylammonium chloride, oxitropium bromide, carbachol, glycopyrrolate, safranin, sinapinic acid, tetraethylammonium bromide, cetyltrimethylammonium bromide, succinylcholine, sphingomyelin, ganglioside GM1, denatonium, fenugreek alkaloids, neostigmine, paraquat, pyridostigmine, phellodendron, pralidoxime iodide, betaine, betaine, carbachol, lecithin and choline. Item 57. The free radical generating catalyst according to Item 51, wherein the ammonium salt represented by the chemical formula (XI) is an ammonium salt represented by the following chemical formula (XIII), In the chemical formula (XIII), R 111 is an alkyl group having 5 to 40 carbon atoms, X - It is an anion. Item 58. The free radical generating catalyst according to any one of Items 51 to 57, wherein the ammonium salt is benzethonium chloride. Item 59. The free radical generating catalyst according to Item 51, wherein the ammonium salt represented by the chemical formula (XI) is an ammonium salt represented by the following chemical formula (XIV), In the chemical formula (XIV), R 100 A cyclic structure may be formed, and the cyclic structure may be a saturated cyclic structure or an unsaturated cyclic structure, may be an aromatic ring or a non-aromatic ring, and may have one or more substituents or may not have one or more substituents; R 11 and X - The same as the chemical formula (XI). Item 60. The free radical generating catalyst according to Item 51, wherein the ammonium salt represented by the chemical formula (XI) is an ammonium salt represented by the following chemical formula (XV), In the chemical formula (XV), Each Z is CH or N, and may be the same or different. In the case of CH, H may be substituted by a substituent; R 11 and X - The same as the chemical formula (XI). Item 61. The free radical generating catalyst according to Item 51, wherein the ammonium salt represented by the chemical formula (XI) is an ammonium salt represented by the following chemical formula (XVI), In the chemical formula (XVI), R 101 , R 102 , R 103 and R 104 are each a hydrogen atom or a substituent, R 101 , R 102 , R 103 and R 104 They can be the same or different. Or, R 101 , R 102 , R 103 and R 104 Two or more of them can be integrated and bonded to N + Together they form a ring structure, which may be a saturated ring structure or an unsaturated ring structure, may be an aromatic ring or a non-aromatic ring, and may or may not have one or more substituents; Z is CH or N. In the case of CH, H may be substituted by a substituent; R 11 and X - The same as the chemical formula (XI). Item 62. The free radical generating catalyst according to Item 51, wherein the ammonium salt represented by the chemical formula (XI) is an ammonium salt represented by the following chemical formula (XVII), In the chemical formula (XVII), R 111 ~R 118 are each a hydrogen atom or a substituent, R 111 ~R 118 They can be the same or different. Or, R 111 ~R 118 Two or more of them may be integrated to form a cyclic structure, and the cyclic structure may be an aromatic ring or a non-aromatic ring, and may or may not have one or more substituents; Z is CH or N. In the case of CH, H may be substituted by a substituent; R 11 and X - The same as the chemical formula (XI). Item 63. A free radical generating catalyst according to Item 51, wherein the ammonium salt is NH4+ of salt. Item 64. A free radical generating catalyst according to Item 63, wherein the ammonium salt is NH4Cl. Item 65. The free radical generating catalyst according to any one of Items 51 to 55, 57 and 59 to 63, wherein the ammonium salt is a hexafluorophosphate salt of the ammonium. Item 66. The free radical generating catalyst according to any one of Items 51 to 65, wherein the free radical generating source is 9- 10-Methylacridine at least one of an ion and a salt thereof, Item 67. The free radical generating catalyst according to any one of Items 1 to 66, characterized in that the reaction rate constant k relative to the following chemical reaction formula (1b) is cat 1.0×10 -5 S -1 , Co Tpp: cobalt(II) tetraphenylporphyrin Q1: Ubiquinone 1 In the chemical formula (1b), M n+ represents the free radical generating catalyst; CoTPP stands for cobalt(II) tetraphenylporphyrin; Q1 represents ubiquinone 1; [(TPP)Co] + represents the tetraphenylporphyrin cobalt(III) cation; (Q1) ·－ Represents the anionic radical of ubiquinone 1. Item 68. A method for producing free radicals, comprising a mixing step of mixing the free radical generating catalyst according to any one of Items 1 to 67 and the free radical generating source. Item 69. The production method according to Item 68, wherein a solvent is further mixed in the mixing step. Item 70. The manufacturing method according to Item 69 or 70, further comprising a light irradiation step of irradiating the mixture obtained by the mixing step with light. Item 71. A method for producing free radicals, comprising: A mixing step of mixing a Lewis acid having a Lewis acidity of 0.4 eV or more and a free radical generating source; and A reaction step of reacting the Lewis acid with the free radical generating source in a non-acidic liquid; The Lewis acid does not include peroxodisulfate, The free radical generating source is at least one selected from halous acid, halite ion and halite salt. Item 72. The production method according to Item 66, wherein the halogenous acid is at least one selected from chlorous acid, bromous acid and iodous acid. Item 73. The manufacturing method according to Item 71 or 72, wherein the free radical generating source is a chlorite ion. Item 74. The method for producing a free radical according to any one of Items 71 to 73, wherein the Lewis acid is the free radical generating catalyst according to any one of Items 34 to 50. Item 75. A method for producing free radicals, comprising: A mixing step of mixing a Lewis acid having a Lewis acidity of 0.4 eV or more, O2, and a free radical generating source; and A reaction step of reacting the Lewis acid, the O2 and the free radical generating source in a liquid; The Lewis acid is a free radical generating catalyst as described in any one of items 51 to 66; The free radical generating source is selected from a nitrogen-containing aromatic cation derivative represented by any one of the formulas (A-1) to (A-8), a 9-substituted acridine represented by the formula (A-9) ion, the quinoline represented by the formula (I) ionic derivatives, their stereoisomers and tautomers, and at least one of their salts. Item 76. The production method according to Item 70, wherein the Lewis acid is the free radical generating catalyst according to Item 66. Item 77. The production method according to any one of Items 71 to 76, wherein a solvent is further mixed in the mixing step. Item 78. The production method according to any one of Items 71 to 77, further comprising a light irradiation step of irradiating the mixture obtained by the mixing step with light. Item 79. A method for producing free radicals, comprising: A mixing step of mixing a Lewis acid having a Lewis acidity of 0.4 eV or more and a free radical generating source; and A reaction step of reacting the Lewis acid and the free radical generating source in a liquid; The Lewis acid does not include peroxodisulfate, The Lewis acid having a Lewis acidity of 0.4 eV or more contains an inorganic substance; The free radical generating source is at least one selected from halous acid, halite ion and halite salt. Item 80. The manufacturing method according to Item 79, wherein the inorganic substance contains metal ions. Item 81. The method according to Item 79, wherein the inorganic substance is selected from alkaline earth metal ions, rare earth ions, Mg 2+ Sc 3+ , Li + , Fe 2+ , Fe 3+ 、Al 3+ , at least one of silicate ions and borate ions. Item 82. A production method according to any one of Items 70 to 73 and 79, wherein the Lewis acid having a Lewis acidity of 0.4 eV or more is at least one selected from AlCl3, AlMeCl2, AlMe2Cl, BF3, BPh3, BMe3, TiCl4, SiF4 and SiCl4. Item 83. The production method according to any one of Items 79 to 82, wherein the halous acid is at least one selected from chlorous acid, bromous acid, and iodous acid. Item 84. The production method according to any one of Items 79 to 83, wherein the free radical generating source is a chlorite ion. Item 85. A method for producing an oxidation reaction product by oxidizing an oxide, characterized in that it comprises: A free radical production step of producing the free radical by the production method described in any one of items 68 to 84; and An oxidation reaction step is to react the oxidized substance with an oxidant by the action of the free radicals to generate the oxidation reaction product. Item 86. The production method according to Item 85, wherein the free radical also serves as the oxidant. Item 87. A pharmaceutical agent, characterized in that it comprises a free radical generating catalyst and a free radical generating source; The radical generating catalyst is the radical generating catalyst described in any one of Items 1 to 67. Item 88. An agent according to Item 87, wherein the free radical generating source comprises an oxygen-containing acid. Item 89. An agent according to Item 88, wherein the oxygen-containing acid is at least one selected from boric acid, carbonic acid, orthocarbonic acid, carboxylic acid, silicic acid, nitrous acid, nitric acid, phosphorous acid, phosphoric acid, arsenic acid, sulfurous acid, sulfuric acid, sulfonic acid, sulfinic acid, chromic acid, dichromic acid, permanganic acid and halogen oxygen-containing acid. Item 90. An agent according to Item 89, wherein the halogen oxygen-containing acid is at least one selected from hypochlorous acid, chlorous acid, chloric acid, perchloric acid, hypobromous acid, bromous acid, bromic acid, perbromic acid, hypoiodous acid, iodous acid, iodic acid and periodic acid. Item 91. An agent according to Item 87, wherein the free radical generating source comprises at least one selected from halogen ions, hypohalite ions, subhalate ions, halide ions and perhalate ions. Item 92. The agent according to Item 88, wherein the oxygen-containing acid is a halogen oxygen-containing acid or a salt thereof. Item 93. The agent according to Item 92, wherein the halogen oxygen-containing acid is a chlorine oxygen-containing acid. Item 94. An agent according to Item 88, wherein the oxygen-containing acid comprises a chlorite ion. Item 95. A liquid agent, characterized in that it contains a free radical generating catalyst and at least one selected from a halous acid, a halite ion and a halite salt; The free radical generating catalyst is the free radical generating catalyst according to any one of items 1 to 30 and 34 to 50, and the Lewis acidity of the free radical generating catalyst is 0.4 eV or more; The liquid medicine is not acidic. Item 96. An agent according to Item 95, wherein the halogenous acid is at least one selected from chlorous acid, bromous acid and iodous acid. Item 97. An agent according to Item 95, wherein the halogenous acid is chlorous acid. Item 98. The agent according to any one of Items 87 to 97, further comprising at least one of water and an organic solvent. Item 99. The agent according to any one of Items 87 to 98, wherein the agent is a fungicide. Item 100. The agent according to any one of Items 87 to 99, wherein the agent is used in vivo. Item 101. The drug according to any one of Items 87 to 100, wherein the drug is used in a digestive organ. Item 102. The agent according to Item 101, wherein the digestive organ is at least one selected from the oral cavity, pharynx, esophagus, stomach, duodenum, small intestine, and large intestine. Item 103. The agent according to Item 101, wherein the digestive organ is the large intestine. Item 104. The agent according to any one of Items 100 to 103, wherein the agent is used for the treatment or symptom suppression of ulcerative colitis. Item 105. The drug according to any one of Items 87 to 104, wherein the drug is an agricultural and livestock drug. Item 106. An agricultural and livestock agent according to Item 105, wherein the agricultural and livestock agent is at least one selected from agricultural fungicides, agricultural antiviral agents, agricultural deodorants, agricultural insecticides, agricultural repellents, agricultural soil improvers, livestock fungicides, livestock antiviral agents, livestock deodorants, livestock insecticides, livestock repellents and livestock soil improvers.

Claims

1. A free radical generating catalyst, characterized in that Contains at least one selected from amino acids, proteins, peptides, phospholipids and salts thereof.

2. The free radical generating catalyst according to claim 1, wherein The free radical generating catalyst further comprises ammonium.

3. The free radical generating catalyst according to claim 2, wherein The ammonium is an ammonium salt represented by the following chemical formula (XI), In the chemical formula (XI), R 11 , R 21 , R 31 and R 41 Each is a hydrogen atom or an aromatic ring, or an alkyl group, the alkyl group may contain an ether bond, a carbonyl group, an ester bond or an amide bond, or an aromatic ring, R 11 , R 21 , R 31 and R 41 They can be the same or different. Or, R 11 , R 21 , R 31 and R 41 Two or more of them can be integrated and bonded to N + Together they form a ring structure, which may be a saturated ring structure or an unsaturated ring structure, may be an aromatic ring or a non-aromatic ring, and may have one or more substituents or may not have one or more substituents; X - It is an anion, which does not include the peroxodisulfate ion.

4. The free radical generating catalyst according to claim 3, wherein The ammonium salt represented by the chemical formula (XI) is an ammonium salt represented by the following chemical formula (XII), In the chemical formula (XII), R 111 is an alkyl group having 5 to 40 carbon atoms, which may contain an ether bond, a keto (carbonyl) group, an ester bond or an amide bond, a substituent group, or an aromatic ring; R 21 and X - The same as the chemical formula (XI).

5. The free radical generating catalyst according to claim 4, wherein The ammonium salt represented by the chemical formula (XII) is an ammonium salt represented by the following chemical formula (XIII), In the chemical formula (XIII), R 111 and X - The same as the chemical formula (XII).

6. The free radical generating catalyst according to claim 4, wherein The ammonium is selected from at least one of benzethonium chloride, benzalkonium chloride, cetyltrimethylammonium chloride, tetramethylammonium chloride, ammonium chloride, methylammonium chloride, tetrabutylammonium chloride, cetylpyridinium chloride, cetyltrimethylammonium bromide, dequalinium chloride, edrophonium chloride, didecyldimethylammonium chloride, benzyltriethylammonium chloride, oxitropium bromide, carbachol, glycopyrrolate, safranin, sinapinic acid, tetraethylammonium bromide, cetyltrimethylammonium bromide, succinylcholine, sphingomyelin, ganglioside GM1, denatonium, trigonelline, neostigmine, paraquat, pyridostigmine, phellodendron, pralidoxime iodide, betaine, betaine, carbachol, betaine red pigment, lecithin, adenine, guanine, cytosine, thymine, uracil and choline.

7. The free radical generating catalyst according to claim 4, wherein The ammonium salt represented by the chemical formula (XII) is benzethonium chloride.

8. The free radical generating catalyst according to claim 3, wherein The ammonium salt represented by the chemical formula (XI) is an ammonium salt represented by the following chemical formula (XIV), In the chemical formula (XIV), R 100 A cyclic structure may be formed, and the cyclic structure may be a saturated cyclic structure or an unsaturated cyclic structure, may be an aromatic ring or a non-aromatic ring, and may have one or more substituents or may not have one or more substituents; R 11 and X - The same as the chemical formula (XI).

9. The free radical generating catalyst according to claim 3, wherein The ammonium salt represented by the chemical formula (XI) is an ammonium salt represented by the following chemical formula (XV), In the chemical formula (XV), Each Z is CH or N, and may be the same or different. In the case of CH, H may be substituted by a substituent; R 11 and X - The same as the chemical formula (XI).

10. The free radical generating catalyst according to claim 3, wherein The ammonium salt represented by the chemical formula (XI) is an ammonium salt represented by the following chemical formula (XVI), In the chemical formula (XVI), R 101 , R 102 , R 103 and R 104 are each a hydrogen atom or a substituent, R 101 , R 102 , R 103 and R 104 They can be the same or different. Or, R 101 , R 102 , R 103 and R 104 Two or more of them can be integrated and bonded to N + Together they form a ring structure, which may be a saturated ring structure or an unsaturated ring structure, may be an aromatic ring or a non-aromatic ring, and may have one or more substituents or may not have one or more substituents; Z is CH or N. In the case of CH, H may be substituted by a substituent; R 11 and X - The same as the chemical formula (XI).

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