Method for producing ester compounds and acetal compounds, and method for cleaving Boc group

Abstract

To provide a method for producing an ester compound from an alcohol compound and a carboxy compound or by an ester exchange reaction, a method for producing an acetal compound, and a cutting method of a Boc group for deprotection, those method achieved without using an organic solvent solution product of hydrogen chloride or hydrogen chloride gas.SOLUTION: Dichloromethane is irradiated with high-energy light in the presence of oxygen to decompose the dichloromethane. A method for producing an ester compound and an acetal compound and a method for cutting a Boc group for deprotection are achieved by using a decomposition product of the dichloromethane. An example is shown by following reactions.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to a method for producing an ester compound from an alcohol compound and a carboxy compound or by a transesterification reaction without using a hydrogen chloride organic solvent solution product or hydrogen chloride gas, a method for producing an acetal compound without using a hydrogen chloride organic solvent solution product or hydrogen chloride gas, and a method for cleaving and deprotecting a Boc group without using a hydrogen chloride organic solvent solution product or hydrogen chloride gas. [Background technology]

[0002] Classically, ester compounds are synthesized by the Fischer ester synthesis reaction in which a composition containing an alcohol compound and a carboxy compound is heated in the presence of an acid catalyst. In this reaction, hydrochloric acid containing water is sometimes used as the acid catalyst. However, this reaction is an equilibrium reaction in which the hydrolysis reaction of the ester compound also occurs at the same time. Therefore, in order to increase the yield of the ester compound, an organic solvent solution of hydrogen chloride is often used as the acid catalyst to reduce the amount of water in the reaction solution. The same is true when synthesizing an ester compound by a transesterification reaction.

[0003] In addition, while the carbonyl group exhibits electrophilicity, the acetal compound obtained by reacting an alcohol compound with a compound having a carbonyl group has low electrophilicity and low nucleophilicity. Therefore, the carbonyl group may be protected by reacting the carbonyl compound with the alcohol compound in the presence of an acid catalyst. Conversely, the hydroxyl group of 1,2-diol or 1,3-diol may be protected with a carbonyl compound. In this case, the acetal compound becomes a hemiacetal compound in the presence of water, and since hemiacetal compounds are generally unstable and return to acetal compounds or carbonyl compounds, an organic solvent solution of hydrogen chloride is often used as the acid catalyst.

[0004] Furthermore, the Boc group (t-butoxycarbonyl group) is widely used as a protecting group for amino groups and hydroxyl groups. In particular, the Boc group is useful for peptide synthesis because it can be cleaved under strong acidic conditions even in the absence of water without cleaving the ester-type protecting group of the carboxyl group, which is hydrolyzed under acidic conditions. Trifluoroacetic acid is also used to cleave the Boc group, but trifluoroacetic acid is highly toxic. Trifluoroacetic acid is particularly toxic to aquatic animals, so its release into the environment is prohibited. Therefore, an organic solvent solution of hydrogen chloride is often used to cleave the Boc group.

[0005] However, commercially available hydrogen chloride-organic solvent solution products are expensive. Alternatively, hydrogen chloride gas could be used, but because hydrogen chloride gas is highly toxic, there are strict regulations regarding its transportation, storage, and use. For example, to use hydrogen chloride gas safely under conditions stipulated by Japanese law without releasing it into the environment, dedicated auxiliary equipment such as a cylinder cabinet for gas cylinders, an acid-resistant draft chamber, a wet scrubber, and sprinklers for accidents are required.

[0006] Incidentally, the present inventor has developed a technology for generating phosgene by irradiating chloroform with high-energy light in the presence of oxygen and using the generated phosgene safely (Patent Document 1, etc.). The present inventor has also demonstrated that 4-bromoanisole can be obtained by irradiating dibromomethane with high-energy light in the presence of oxygen and then adding anisole (Patent Document 1). In the addition reaction of a bromo group to a benzene ring, mainly bromine (Br 2 ) is used, it is believed that in this reaction dibromomethane is decomposed to produce bromine. [Prior art documents] [Patent documents]

[0007] [Patent Document 1] JP 2013-181028 A Summary of the Invention [Problem to be solved by the invention]

[0008] As described above, hydrogen chloride-organic solvent solutions are mainly used for synthesizing ester compounds and acetal compounds and for cleaving Boc groups, but hydrogen chloride-organic solvent solution products are expensive and it is difficult to use hydrogen chloride gas. Therefore, an object of the present invention is to provide a method for producing an ester compound from an alcohol compound and a carboxy compound or by a transesterification reaction, without using a hydrogen chloride organic solvent solution product or hydrogen chloride gas, a method for producing an acetal compound, without using a hydrogen chloride organic solvent solution product or hydrogen chloride gas, and a method for cleaving and deprotecting a Boc group, without using a hydrogen chloride organic solvent solution product or hydrogen chloride gas. [Means for solving the problem]

[0009] The present inventors have conducted extensive research to solve the above problems, and as a result, have found that by using a decomposition product of dichloromethane obtained by irradiating dichloromethane with high-energy light in the presence of oxygen, it is possible to synthesize ester compounds or acetal compounds and cleave Boc groups in the same manner as in the case of using a hydrogen chloride-organic solvent solution or hydrogen chloride gas, and have thus completed the present invention. The present invention will now be described.

[0010] [1] A method for producing an ester compound, comprising: A step of irradiating dichloromethane with high-energy light in the presence of oxygen to decompose the dichloromethane; and A method comprising the step of reacting a carboxylic acid compound with an alcohol compound in the presence of a decomposition product of dichloromethane. [2] The method according to the above [1], wherein a composition containing dichloromethane and the alcohol compound is irradiated with high-energy light in the presence of oxygen to decompose the dichloromethane, and then the carboxylic acid compound is added. [3] The method according to the above [1], wherein a composition containing dichloromethane, the carboxylic acid compound and the alcohol compound is irradiated with high-energy light in the presence of oxygen.

[0011] [4] A method for producing an ester compound, comprising: the ester compound is an ester compound of a carboxylic acid and an alcohol A, A step of irradiating dichloromethane with high-energy light in the presence of oxygen to decompose the dichloromethane; and A method comprising the step of reacting an ester compound of an alcohol B different from the alcohol A with an alcohol A in the presence of a decomposition product of dichloromethane. [5] The method according to [4] above, comprising irradiating a composition containing dichloromethane, an ester compound of the alcohol B, and the alcohol A with high-energy light in the presence of oxygen.

[0012] [6] A method for producing an acetal compound, comprising: A step of irradiating dichloromethane with high-energy light in the presence of oxygen to decompose the dichloromethane; and A method comprising the step of reacting a carbonyl compound with an alcohol compound in the presence of a decomposition product of dichloromethane.

[0013] [7] A method for deprotecting a compound having an amino group and / or a hydroxyl group protected by a Boc group by cleaving the Boc group, comprising the steps of: A step of irradiating dichloromethane with high-energy light in the presence of oxygen to decompose the dichloromethane; and The method comprises the step of deprotecting the compound by cleaving the Boc group in the presence of a decomposition product of dichloromethane.

[0014] [8] The method according to any one of the above [1] to [7], wherein the high-energy light comprises light having a wavelength of 180 nm or more and 280 nm or less. Effect of the Invention

[0015] According to the method of the present invention, it is possible to carry out the same reactions as those using hydrogen chloride-organic solvent solution or hydrogen chloride gas, such as synthesis of ester compounds and acetal compounds and cleavage of Boc groups, without using hydrogen chloride-organic solvent solution or hydrogen chloride gas. In addition, the decomposition product of dichloromethane used in the method of the present invention can be safely and easily obtained under very simple conditions of irradiating dichloromethane with high-energy light in the presence of oxygen. Therefore, the present invention is industrially very excellent as an alternative method to reactions using expensive hydrogen chloride-organic solvent solution or dangerous hydrogen chloride gas. [Brief description of the drawings]

[0016] [Figure 1] FIG. 1 is a schematic diagram showing an example of the configuration of a reaction apparatus used in the present invention. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0017] In the present invention, dichloromethane is decomposed by irradiating it with high-energy light in the presence of oxygen. The present inventor has previously irradiated chloroform with high-energy light in the presence of oxygen to decompose chloroform and generate mainly phosgene, which is utilized for the production of carbonate compounds and the like. In contrast, in the present invention, when this step is carried out in the coexistence of a carboxylic acid compound and an alcohol compound, an ester compound is obtained as the main product, and the generation of a carbonate compound is not or is hardly confirmed, so that no or little phosgene is generated. In addition, according to the present invention, the esterification reaction, acetalization reaction, and Boc cleavage reaction promoted by an acid catalyst are promoted, so that dichloromethane is decomposed to generate hydrogen chloride, but it is not necessarily clear what kind of compound is the decomposition product of dichloromethane.

[0018] Examples of the oxygen source include air and purified oxygen gas. The purified oxygen gas may be mixed with an inert gas such as nitrogen gas or argon. From the viewpoints of cost and ease of preparation, the oxygen source is preferably air. From the viewpoint of increasing the decomposition efficiency of dichloromethane by light irradiation, the oxygen content in the oxygen source is preferably 15% by volume or more and 100% by volume or less. Even when oxygen gas with an oxygen content of 100% by volume is used, the oxygen content may be controlled within the above range by adjusting the oxygen flow rate into the reaction system. The method of supplying the gas containing oxygen is not particularly limited, and the gas may be supplied into the reaction system from an oxygen cylinder equipped with a flow rate regulator, or may be supplied into the reaction system from an oxygen generator.

[0019] Incidentally, "in the presence of oxygen" may refer to either a state in which dichloromethane or the like is in contact with oxygen, or a state in which oxygen is present in a composition containing dichloromethane. Thus, the reaction according to the present invention may be carried out under a stream of a gas containing oxygen, but from the viewpoint of increasing the reaction yield, it is preferable to supply the gas containing oxygen by bubbling into dichloromethane or a composition containing dichloromethane.

[0020] The amount of the gas containing oxygen is appropriately determined according to the amount of dichloromethane, the shape of the reaction vessel, etc., and the amount of gas supplied to the reaction vessel per minute relative to the dichloromethane present in the reaction vessel is preferably 5 volume times or more. The amount is more preferably 25 volume times or more, and even more preferably 50 volume times or more. The upper limit of the amount is not particularly limited, but is preferably 500 volume times or less, more preferably 250 volume times or less, and particularly preferably 150 volume times or less. In addition, the amount of oxygen supplied to the reaction vessel per minute relative to the dichloromethane present in the reaction vessel is preferably 5 volume times or more and 25 volume times or less. If the gas flow rate is too high, dichloromethane may volatilize, and if it is too low, the reaction may not proceed easily. The supply rate of oxygen can be, for example, 0.1 L / min or more and 10 L / min or less.

[0021] As the high-energy light to be irradiated to dichloromethane or a composition containing dichloromethane, light containing short wavelength light is preferred, light containing ultraviolet light is more preferred, and more specifically light containing light with a wavelength of 180 nm or more and 500 nm or less, and light with a peak wavelength of 180 nm or more and 500 nm or less are preferred. The wavelength of the high-energy light may be appropriately determined, but 400 nm or less is more preferred, and 300 nm or less is even more preferred, and light with a peak wavelength within these ranges is also preferred. When the irradiated light contains light in the above wavelength range, dichloromethane can be efficiently oxidatively photodecomposed. For example, light containing UV-B with a wavelength of 280 nm or more and 315 nm or less and / or UV-C with a wavelength of 180 nm or more and 280 nm or less can be used, and light containing UV-C with a wavelength of 180 nm or more and 280 nm or less is preferred, and light with a peak wavelength within these ranges is also preferred.

[0022] The means of light irradiation is not particularly limited as long as it can irradiate light of the above wavelength, and examples of light sources that include light in this wavelength range include sunlight, low-pressure mercury lamps, medium-pressure mercury lamps, high-pressure mercury lamps, ultra-high-pressure mercury lamps, chemical lamps, black light lamps, metal halide lamps, LED lamps, etc. From the standpoint of reaction efficiency and cost, low-pressure mercury lamps are preferably used.

[0023] The conditions such as the intensity of the irradiated light and the irradiation time may be appropriately set depending on the type and amount of the starting material. For example, the desired light intensity at the shortest distance from the light source to the dichloromethane or the composition containing dichloromethane is 1 mW / cm 2 More than 50mW / cm 2The light irradiation time is preferably 0.5 hours or more and 10 hours or less. The irradiation time is more preferably 1 hour or more, more preferably 2 hours or more, more preferably 6 hours or less, and even more preferably 4 hours or less. The light irradiation mode is not particularly limited, and any mode can be adopted, such as a mode in which light is continuously irradiated from the start of the reaction to the end, a mode in which light irradiation and non-light irradiation are alternately repeated, and a mode in which light is irradiated only for a predetermined time from the start of the reaction. When light irradiation and non-light irradiation are alternately repeated, the decomposition of dichloromethane and the reaction promoted by the dichloromethane decomposition product are alternately performed, so that the reaction may be promoted well. In addition, the shortest distance between the light source and the halogenated methane is preferably 1 m or less, more preferably 50 cm or less, and even more preferably 10 cm or less or 5 cm or less. The lower limit of the shortest distance is not particularly limited, but it may be 0 cm, that is, the light source may be immersed in dichloromethane or a composition containing dichloromethane.

[0024] The temperature during the reaction may be appropriately adjusted, for example, to 0° C. or higher and 50° C. or lower. The temperature is preferably 10° C. or higher, more preferably 20° C. or higher, and is preferably 40° C. or lower, more preferably 30° C. or lower.

[0025] The reaction apparatus that can be used in the method of the present invention includes a reaction vessel equipped with a high-energy light irradiation means. FIG. 1 shows one embodiment of the reaction apparatus that can be used in the method of the present invention. The reaction apparatus shown in FIG. 1 has a light irradiation means 2 in a reaction vessel 1, and the reaction vessel is immersed in a water bath 3 for temperature control. At least dichloromethane is added to the reaction vessel 1, and a gas containing at least oxygen is supplied to the reaction vessel 1, or a gas containing oxygen is bubbled into the reaction liquid of the mixture. The reaction is carried out by irradiating the reaction liquid with high-energy light using the high-energy light irradiation means 2. The high-energy light irradiation means 2 is preferably covered with a jacket 4 made of glass or the like to prevent corrosion due to acids generated by decomposition of dichloromethane. The temperature of the reaction liquid is preferably controlled to a constant or approximately constant temperature using a water bath 3. The reaction liquid may be stirred with a stirrer 5. Since the reaction often involves heat generation, it is preferable to install a cooling tube 6 in the reaction vessel. Even if the generated dichloromethane decomposition product is vaporized by heat, it can be liquefied by the cooling tube 6 and recycled to the reaction liquid. Furthermore, in order to prevent excess dichloromethane and its decomposition products from leaking out of the reaction system, it is preferable to introduce the gas discharged from the reaction vessel 1 into a trap for capturing dichloromethane and its decomposition products.

[0026] Since some alcohol compounds are liquid at room temperature and pressure and can be used as solvents, the decomposition step of dichloromethane may be carried out in the coexistence of an alcohol compound. Examples of the alcohol compound include compounds represented by the formula R 1 (OH) m (In the formula, R 1 represents an m-valent organic group, and m represents an integer of 1 or more and 5 or less.

[0027] R in alcohol compound (I) 1 R represents an m-valent organic group. Monovalent organic groups will be described below as representative examples. 1 As the monovalent organic group, for example, C 1-10 Monovalent aliphatic hydrocarbon group, C 3-10 Monovalent cycloaliphatic hydrocarbon radical, C 6-15Examples of such groups include monovalent aromatic hydrocarbon groups and monovalent organic groups formed by bonding two or more and five or less of these groups.

[0028] "C 1-10 The term "monovalent chain aliphatic hydrocarbon group" refers to a linear or branched monovalent saturated or unsaturated aliphatic hydrocarbon group having 1 to 10 carbon atoms. For example, C 1-10 As the monovalent chain aliphatic hydrocarbon group, C 1-10 Alkyl group, C 2-10 Alkenyl groups, and C 2-10 Mention may be made of alkynyl groups.

[0029] C 1-10 Examples of the alkyl group include methyl, ethyl, n-propyl, isopropyl, n-butyl, 1-methylpropyl, 2-methylpropyl, 1,1-dimethylethyl, 2,2-dimethylethyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, and n-decyl. 1-8 Alkyl group or C 1-6 is an alkyl group, more preferably C 1-4 Alkyl group or C 1-2 It is preferably an alkyl group, and even more preferably methyl.

[0030] C 2-10 Examples of alkenyl groups include ethenyl (vinyl), 1-propenyl, 2-propenyl (allyl), butenyl, hexenyl, octenyl, decenyl, etc. 2-8 alkenyl group, more preferably C 2-6 Alkenyl group or C 2-4 alkenyl groups, even more preferably ethenyl (vinyl) or 2-propenyl (allyl). 2-10 Examples of monohydric alcohol compounds having an alkenyl group include rhodinol, geraniol, nerol, linalool, and geraniol.

[0031] C 2-10Examples of the alkynyl group include ethynyl, propynyl, butynyl, hexynyl, octynyl, and pentadecynyl. 2-8 Alkynyl groups, more preferably C 2-6 Alkynyl group or C 2-4 It is an alkynyl group.

[0032] "C 3-10 The term "monovalent cyclic aliphatic hydrocarbon group" refers to a cyclic monovalent saturated or unsaturated aliphatic hydrocarbon group having 1 to 10 carbon atoms. For example, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkenyl groups, and C 3-10 Cycloalkynyl groups are also included. 3-10 Examples of the cycloalkyl group include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and adamantyl. 3-10 Cycloalkenyl groups include, for example, cyclopropene, cyclobutene, cyclopentadiene, and cyclohexene.

[0033] "C 6-15 The term "monovalent aromatic hydrocarbon group" refers to a monovalent aromatic hydrocarbon group having 6 to 15 carbon atoms. Examples of the monovalent aromatic hydrocarbon group include phenyl, indenyl, naphthyl, biphenyl, phenalenyl, phenanthrenyl, anthracenyl, and the like, and preferably C 6-12 It is a monovalent aromatic hydrocarbon group, more preferably phenyl.

[0034] C 1-10 Monovalent aliphatic hydrocarbon group, C 3-10 Monovalent cyclic aliphatic hydrocarbon radicals, and C 6-15 Examples of the monovalent organic group having two or more and five or less groups selected from monovalent aromatic hydrocarbon groups bonded thereto include C 3-10 Monovalent cycloaliphatic hydrocarbon group -C 1-10 Monovalent aliphatic hydrocarbon group, C 1-10 Monovalent aliphatic hydrocarbon group -C 3-10 Monovalent cycloaliphatic hydrocarbon radical, C 6-15 Monovalent aromatic hydrocarbon radical -C 1-10 Monovalent aliphatic hydrocarbon group, C 1-10Monovalent aliphatic hydrocarbon group -C 6-15 Monovalent aromatic hydrocarbon radicals, C 1-10 Monovalent aliphatic hydrocarbon group -C 3-10 Monovalent cycloaliphatic hydrocarbon group -C 1-10 Monovalent aliphatic hydrocarbon group, C 3-10 Monovalent cycloaliphatic hydrocarbon group -C 1-10 Monovalent aliphatic hydrocarbon group -C 3-10 Monovalent cyclic aliphatic hydrocarbon radicals, and C 1-10 Monovalent aliphatic hydrocarbon group -C 6-15 Monovalent aromatic hydrocarbon radical -C 1-10 Examples of such groups include monovalent chain aliphatic hydrocarbon groups.

[0035] The monovalent organic group in the alcohol compound (I) may be substituted with a substituent. 1-10 The substituent α of the monovalent chain aliphatic hydrocarbon group is, for example, 1-6 Alkoxy groups, halogeno groups, ether groups (-O-), thioether groups (-S-), carbonyl groups (-C(=O)-), and tri(C 1-6 and C 3-10 The substituent β of the monovalent cyclic aliphatic hydrocarbon group is, for example, C 1-6 Alkyl group, C 1-6 Alkoxy groups, halogeno groups, ether groups, thioether groups, carbonyl groups, and tri(C 1-6 and C 6-15 The substituent γ of the monovalent aromatic hydrocarbon group is, for example, C 1-6 Alkyl group, C 1-6 The substituents include one or more selected from an alkoxy group and a halogeno group. The ether group, the thioether group, and the carbonyl group are substituted by being inserted between the carbon atoms of the hydrocarbon chain. 1-6 An example of the alkylsilyl group is a trimethylsilyl group.

[0036] "C 1-6The term "alkyl group" refers to a linear or branched monovalent saturated aliphatic hydrocarbon group having 1 to 6 carbon atoms. Examples include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, s-butyl, t-butyl, n-pentyl, and n-hexyl. 1-4 is an alkyl group, more preferably C 1-2 It is an alkyl group, most preferably methyl.

[0037] "C 1-6 The term "alkoxy group" refers to a linear or branched saturated aliphatic hydrocarbon oxy group having 1 to 6 carbon atoms. Examples include methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, t-butoxy, n-pentoxy, n-hexoxy, and the like, and preferably C 1-4 is an alkoxy group, more preferably C 1-2 It is an alkoxy group.

[0038] The halogeno groups include one or more halogeno groups selected from fluoro, chloro, bromo, and iodo.

[0039] Other R in alcohol compounds (I) 1 The monovalent organic group of the formula R 22 -[-XR 21 -] r - (X represents O or S, preferably O, R 21 is C 2-8 R represents an alkanediyl group. 22 is C 1-6 represents an alkyl group, and r represents an integer of 1 or more and 180 or less.

[0040] R 21 As an example, the ethylene group (-CH 2 CH 2 -), propylene group [-CH(CH 3 )CH 2 -or-CH 2 CH(CH 3 )-], and the tetramethylene group (-CH 2 CH 2CH 2 CH 2 -) are mentioned.

[0041] r is preferably 5 or more, more preferably 10 or more, and even more preferably 20 or more, and is preferably 160 or less, and more preferably 150 or less.

[0042] When m in the alcohol compound (I) is 2 or more, the monovalent organic group is to be read as an m-valent organic group. For example, when m is 2, C 1-10 Alkyl groups are C 1-10 In the alkanediyl group, when m is 3, 1-10 Alkyl groups are C 1-10 The formula R can be read as an alkanetriyl group. 22 -[-XR 21 -] r - is a group of the formula -[-XR 21 -] r --It can be.

[0043] Examples of the alcohol compound (I) in which m is 2 include glycol compounds such as 1,2-ethanediol, 1,2-propanediol, 1,3-propanediol, 1,4-butanediol, diethylene glycol, triethylene glycol, tetraethylene glycol, polyethylene glycol, polypropylene glycol, polytetramethylene ether glycol, and polycarbonate diol; dihydroxybenzene compounds such as catechol and resorcinol; dihydroxyheteroaryl compounds such as 4,6-dihydroxy-2-methylpyrimidine and 3,6-dihydroxy-4-methylpyridazine; bisphenol compounds such as bisphenol A, bisphenol AP, bisphenol B, bisphenol BP, bisphenol E, bisphenol F, bisphenol TMC, and bisphenol Z; and sugar alcohol dehydrates such as isosorbide and isomannide. Examples of the alcohol compound (I) in which m is 3 include glycerin, and examples of the alcohol compound (I) in which m is 4 include erythritol, pentaerythritol, and ribose. Examples of the alcohol compound (I) in which m is 5 or more include sugars such as glucose, galactose, ketose, lactose, and sucrose.

[0044] The amount of the alcohol compound used may be appropriately adjusted, and may be, for example, 1 volume or more and 20 volumes or less relative to the initial amount of dichloromethane.

[0045] The esterification reaction of the carboxylic acid compound is promoted by the addition of a proton to the carboxy group. Therefore, the carboxylic acid compound may be added after the decomposition step of dichloromethane, or the decomposition step of dichloromethane may be carried out in the presence of the carboxylic acid compound. The carboxylic acid compound may be, for example, a compound represented by the formula R 2 (CO 2 H) n (In the formula, R 2 R represents an n-valent organic group, and n represents an integer of 1 to 5.) can be used as the carboxylic acid compound (II). 2 is R in the alcohol compound (I). 1When m and n are the same, R 2 and R 1 may be the same or different from each other.

[0046] The amount of the carboxylic acid compound used may be adjusted appropriately, and may be, for example, 0.5 times or more by mole and 2 times or less by mole per mole of the alcohol compound. For example, the carboxylic acid compound and the alcohol compound that are easier to synthesize or less expensive may be used in greater amounts. The molar ratio is preferably 0.8 times or more by mole, more preferably 0.9 times or more by mole, and more preferably 1.2 times or less by mole, and more preferably 1.1 times or less by mole. In addition, when the alcohol compound is also used as a solvent, the molar ratio of the carboxylic acid compound to 1 mole of the alcohol compound may be 0.01 times or more by mole and 0.1 times or less by mole.

[0047] For example, monocarboxylic acid compounds (II 1 ) and monohydric alcohol compounds (I 1 The esterification reaction according to the present invention using the above-mentioned ester is represented by the following formula:

[0048] [ka] [In the formula, R 1 and R 2 each independently represents a monovalent organic group. In addition, divalent carboxylic acid compounds (II 2 ) and dihydric alcohol compounds (I 2 ) to obtain polyesters by the esterification reaction according to the present invention.

[0049] [ka] [In the formula, R 1 and R 2 each independently represents a divalent organic group.

[0050] Furthermore, for example, monovalent carboxylic acid compounds (II 1 ) and trihydric alcohol compounds (I3 The esterification reaction according to the present invention using the above-mentioned ester is represented by the following formula:

[0051] [ka] [In the formula, R 1 represents a trivalent organic group, and R 2 represents a monovalent organic group.

[0052] The carboxylic acid compound and the alcohol compound may be added after the decomposition step of dichloromethane, or the decomposition step of dichloromethane may be carried out in the coexistence of dichloromethane and a carboxylic acid compound, or the decomposition step of dichloromethane may be carried out in the coexistence of dichloromethane and an alcohol compound, or the decomposition step of dichloromethane may be carried out in the coexistence of dichloromethane, a carboxylic acid compound, and an alcohol compound.

[0053] In addition, after the decomposition step of dichloromethane, the light irradiation and the oxygen supply may be stopped, and then the carboxylic acid compound and the alcohol compound may be reacted. Even after the light irradiation and the oxygen supply are stopped, the decomposition product of dichloromethane remains in the reaction system, so the reaction between the carboxylic acid compound and the alcohol compound is promoted. Furthermore, by stopping the light irradiation and the oxygen supply, further decomposition and volatilization of the decomposition product of dichloromethane may be suppressed.

[0054] The reaction temperature after the light irradiation and oxygen supply are stopped may be the same as the temperature in the decomposition step of dichloromethane, or may be increased to promote the reaction. The reaction temperature after the light irradiation and oxygen supply are stopped may be, for example, 20°C or higher and 120°C or lower. The temperature is preferably 30°C or higher, more preferably 40°C or higher, and is preferably 100°C or lower or 80°C or lower, and more preferably 60°C or lower. Alternatively, the reaction may be carried out under heating reflux conditions.

[0055] The reaction time after the light irradiation and oxygen supply are stopped may be appropriately adjusted within a range in which the reaction proceeds sufficiently, and may be, for example, 1 hour or more and 100 hours or less.

[0056] The present invention can also be applied to transesterification. That is, a dichloromethane decomposition step is performed, and a p-valent ester compound (III) is produced in the presence of the decomposition product of dichloromethane, as shown in the following reaction formula, for example. 1 ) and monohydric alcohol compounds (IV 1 ) to give an ester compound (V 1 ) or a monovalent ester compound (III 2 ) and q-hydric alcohol compounds (IV 2 ) to give an ester compound (V 2 Of course, it is also possible to carry out an ester exchange reaction between a monohydric ester compound and a monohydric alcohol compound.

[0057] [ka] [In the formula, R 3 represents a p-valent organic group, R 4 ~R 7 each independently represents a monovalent organic group, R 8 represents an organic group having a valence of q, p is an integer of 1 to 5, q is an integer of 1 to 5, However, R 4 and R 5 are not the same organic group, R 7 and R 8 are not the same organic group. R in the above reaction formula 3 ~R 8 As for the R in the alcohol compound (I), 1 Among these, organic groups having the same valence can be mentioned.

[0058] The amounts of the ester compound (III) and the alcohol compound (IV) in the transesterification reaction may be appropriately adjusted within a range in which the reaction proceeds well. For example, the amount of the alcohol compound (IV) used relative to the initial amount of dichloromethane may be 1 volumetrically greater or equal to 20 volumetrically less. In addition, with regard to the amount of the ester compound (III), it is preferable to use an excess amount of either the ester compound (III) or the alcohol compound (IV) in order to promote the transesterification reaction. For example, the molar ratio of the ester compound (III) or the alcohol compound (IV) to 1 mole of the other may be 0.01 moles or greater or equal to 0.1 moles or less.

[0059] In the transesterification reaction, the ester compound (III) and the alcohol compound (IV) may also be added after the decomposition step of dichloromethane. Alternatively, the decomposition step of dichloromethane may be carried out in the coexistence of dichloromethane and the ester compound (III), or in the coexistence of dichloromethane and the alcohol compound (IV), or in the coexistence of dichloromethane, the ester compound (III) and the alcohol compound (IV).

[0060] In addition, after the decomposition step of dichloromethane, the light irradiation and oxygen supply may be stopped, and then the ester compound (III) and the alcohol compound (IV) may be reacted. Since the decomposition products of dichloromethane remain in the reaction system even after the light irradiation and oxygen supply are stopped, the reaction between the ester compound (III) and the alcohol compound (IV) is promoted. Furthermore, by stopping the light irradiation and the oxygen supply, further decomposition and volatilization of the decomposition products of dichloromethane may be suppressed.

[0061] The reaction temperature after the light irradiation and oxygen supply are stopped may be the same as the temperature in the decomposition step of dichloromethane, or may be increased to promote the reaction. The reaction temperature after the light irradiation and oxygen supply are stopped may be, for example, 20°C or higher and 120°C or lower. The temperature is preferably 30°C or higher, more preferably 40°C or higher, and is preferably 100°C or lower or 80°C or lower, and more preferably 60°C or lower. Alternatively, the reaction may be carried out under heating reflux conditions.

[0062] The reaction time after the light irradiation and oxygen supply are stopped may be appropriately adjusted within a range in which the reaction proceeds sufficiently, and may be, for example, 1 hour or more and 100 hours or less.

[0063] The present invention can also be applied to a reaction for obtaining an acetal compound from a carbonyl compound and an alcohol compound. That is, a decomposition step of dichloromethane is carried out, and in the presence of the decomposition product of dichloromethane, for example, the carbonyl compound (VI) is reacted with the alcohol compound (VII) as shown in the following reaction formula to produce the acetal compound (VIII). Note that, when 1,2-ethanediol or 1,3-propanediol is used as the alcohol compound as shown in the following formula, a stable 2,5-dioxolane structure or 2,6-dioxane structure is formed.

[0064] [ka] [In the formula, R 9 ~R 11 each independently represents a monovalent organic group, t stands for 2 or 3.]

[0065] R in the above reaction formula 9 ~R 11 Examples of the monovalent organic group include the monovalent organic group in the alcohol compound (I).

[0066] The amounts of the carbonyl compound and the alcohol compound may be appropriately adjusted within a range in which the reaction proceeds well. For example, since the alcohol compound is generally cheaper and may also be used as a solvent, the ratio of the alcohol compound to 1 mole of the carbonyl compound may be set to 2 to 50 moles.

[0067] In the synthesis reaction of an acetal compound, the carbonyl compound and the alcohol compound may be added after the decomposition step of dichloromethane. However, since the activity of the hydroxyl group of the alcohol compound may be increased by the acid catalyst, the decomposition step of dichloromethane may be carried out in the coexistence of dichloromethane and the alcohol compound, or the decomposition step of dichloromethane may be carried out in the coexistence of dichloromethane with the carbonyl compound and the alcohol compound.

[0068] In addition, after the decomposition step of dichloromethane, the light irradiation and oxygen supply may be stopped, and then the carbonyl compound and the alcohol compound may be reacted. Since the decomposition products of dichloromethane remain in the reaction system even after the light irradiation and oxygen supply are stopped, the reaction of the carbonyl compound and the alcohol compound is promoted. In addition, by stopping the light irradiation and oxygen supply, further decomposition and volatilization of the decomposition products of dichloromethane may be suppressed.

[0069] The reaction temperature after the light irradiation and oxygen supply are stopped may be the same as the temperature in the decomposition step of dichloromethane, or may be increased to promote the reaction. The reaction temperature after the light irradiation and oxygen supply are stopped may be, for example, 20°C or higher and 120°C or lower. The temperature is preferably 30°C or higher, more preferably 40°C or higher, and is preferably 100°C or lower or 80°C or lower, and more preferably 60°C or lower. Alternatively, the reaction may be carried out under heating reflux conditions.

[0070] The reaction time after the light irradiation and oxygen supply are stopped may be appropriately adjusted within a range in which the reaction proceeds sufficiently, and may be, for example, 1 hour or more and 100 hours or less.

[0071] The present invention can also be applied to the cleavage of a protecting group, the Boc group. The Boc group is a common protecting group for amino and hydroxyl groups, and can be cleaved under acidic conditions. However, when deprotecting with an acid containing water, such as hydrochloric acid, a protecting group that is cleaved by hydrolysis, such as an ester-based carboxyl protecting group, is cleaved at the same time, and selective deprotection may not be possible. In contrast, according to the present invention, Boc can be selectively protected without the intervention of water. Therefore, the method for cleaving a Boc group according to the present invention is particularly useful for deprotecting amino acids and peptides whose amino and / or hydroxyl groups are protected by a Boc group.

[0072] For example, the deprotection method by cleavage of Boc according to the present invention is shown in the following scheme. [ka] [In the formula, R 12 and R 13 each independently represents a monovalent organic group, R 14 indicates an amino acid side chain group, R 15 OH, OR 16 (In the formula, R 16 represents a protecting group or carrier for the carboxy group), or -[-NH-CHR 17 -C(=O)-] s -R 18 (In the formula, R 17 indicates an amino acid side chain, and R 18 OH, or OR 19 (In the formula, R 19 represents a protecting group for a carboxy group or a carrier, s represents an integer of 1 or more, and when s is an integer of 2 or more, a plurality of R 17 may be the same or different).

[0073] R 12 and R 13 As the monovalent organic group, R in the alcohol compound (I) 1 Among these, the monovalent organic groups may be the same as or different from each other.

[0074] Examples of the carboxy-protecting group include general protecting groups for the carboxy group in amino acids, such as methyl ester, ethyl ester, cyclohexyl ester, phenacyl ester, and allyl ester.

[0075] Examples of supports include supports commonly used in solid-phase peptide synthesis, such as Fmoc-AA-Wang resin, NovaSyn TGA resin, Rink amide PEGA resin, NovaSyn TGR resin, Rink Amide AM resin, Rink Amide AM resin, Rink Amide NovaGel, 2-Chlorotrityl chloride resin, NovaSyn TGT alcohol resin, and Sieber Amide resin.

[0076] Reactive groups contained in the amino acid side groups may be protected with protecting groups commonly used in peptide synthesis.

[0077] In the deprotection method according to the present invention, dichloromethane is irradiated with high-energy light in the presence of oxygen to decompose the dichloromethane, and the decomposition product of dichloromethane is used to cleave the Boc group from a compound having an amino group and / or a hydroxyl group protected by a Boc group (hereinafter referred to as an "amino group / hydroxyl group-containing compound"), thereby deprotecting the amino group / hydroxyl group-containing compound.

[0078] When the amino group / hydroxyl group-containing compound cannot be sufficiently dissolved in dichloromethane alone, a solvent capable of adequately dissolving the amino group / hydroxyl group-containing compound may be used. Examples of such solvents include nitrile-based solvents such as acetonitrile; ether-based solvents such as diethyl ether, methyl ethyl ether, tetrahydrofuran, and dioxane; amide-based solvents such as dimethylformamide and dimethylacetamide; and ketone-based solvents such as acetone and methyl ethyl ketone.

[0079] The amounts of the amino group / hydroxyl group-containing compound, dichloromethane, and solvent may be appropriately adjusted within a range in which the amino group / hydroxyl group-containing compound is sufficiently dissolved, and for example, the amount of the amino group / hydroxyl group-containing compound relative to the total amount of dichloromethane and solvent used may be 1 mg / mL or more and 500 mg / mL or less. The amount is preferably 5 mg / mL or more, more preferably 10 mg / mL or more, even more preferably 20 mg / mL or more, and preferably 200 mg / mL or less, more preferably 100 mg / mL or less, and even more preferably 50 mg / mL or less.

[0080] In the cleavage reaction of the Boc group, the amino group / hydroxyl group-containing compound may be added after the decomposition step of dichloromethane, but dichloromethane may be decomposed in the coexistence of dichloromethane and the amino group / hydroxyl group-containing compound.

[0081] In addition, after the decomposition step of dichloromethane, the light irradiation and oxygen supply may be stopped, and then the cleavage of the Boc group from the amino group / hydroxyl group-containing compound may be continued using the decomposition product of dichloromethane, or the amino group / hydroxyl group-containing compound may be added to perform deprotection. Since the decomposition product of dichloromethane remains in the reaction system even after the light irradiation and oxygen supply are stopped, the cleavage reaction of the Boc group from the amino group / hydroxyl group-containing compound is promoted. Furthermore, the cessation of the light irradiation and oxygen supply may suppress further decomposition and volatilization of the decomposition product of dichloromethane.

[0082] The reaction temperature after the light irradiation and oxygen supply are stopped may be the same as the temperature in the decomposition step of dichloromethane, or may be increased to promote the reaction. The reaction temperature after the light irradiation and oxygen supply are stopped may be, for example, 20°C or higher and 120°C or lower. The temperature is preferably 30°C or higher, more preferably 40°C or higher, and is preferably 100°C or lower or 80°C or lower, and more preferably 60°C or lower. Alternatively, the reaction may be carried out under heating reflux conditions.

[0083] The reaction time after the light irradiation and oxygen supply are stopped may be appropriately adjusted within a range in which the reaction proceeds sufficiently, and may be, for example, 1 hour or more and 100 hours or less.

[0084] In the method of the present invention, a general post-treatment may be carried out after the reaction. For example, the reaction solution may be neutralized by adding an aqueous sodium hydrogen carbonate solution, separated, and the organic phase may be dried with anhydrous magnesium sulfate or anhydrous sodium sulfate, and then concentrated. When the amount of the organic phase is small during separation, a water-insoluble organic solvent such as dichloromethane, chloroform, or ethyl acetate may be added. Alternatively, saturated saline may be used instead of the aqueous sodium hydrogen carbonate solution, or the organic phase may be washed with an aqueous sodium hydrogen carbonate solution, saturated saline solution, water, or the like. The target compound may be further purified from the obtained concentrate by chromatography, recrystallization, or the like.

[0085] Alternatively, when the target compound is a solid at room temperature, a poor solvent such as n-hexane may be added to the reaction solution after the reaction to precipitate the target compound, which may then be collected by filtration, washed with the poor solvent, and dried. The target compound thus obtained may be further purified by chromatography, recrystallization, or the like. EXAMPLES

[0086] The present invention will be described in more detail below with reference to examples. However, the present invention is not limited to the following examples, and it is possible to carry out the present invention by making appropriate modifications within the scope of the above and below-mentioned aims, and all of these modifications are included in the technical scope of the present invention.

[0087] Example 1: Synthesis of methyl acetate [ka] A reaction system was constructed by placing a quartz glass jacket with a diameter of 30 mm inside a cylindrical reaction vessel with a diameter of 42 mm and a capacity of 100 mL, and placing a low-pressure mercury lamp ("UVL20PH-6" manufactured by SEN Light, 20 W, φ24 × 120 mm) inside the quartz glass jacket. A cooler (0 °C) was attached to the cylindrical reaction vessel to re-liquefy the vaporized reaction reagents and solvent. A schematic diagram of the reaction system is shown in Figure 1. The light irradiated from the low-pressure mercury lamp contained UV-C with a wavelength of 254 nm, and the illuminance of the light with a wavelength of 254 nm at a position 5 mm from the tube wall was 6.23 to 9.07 mW / cm. 2 It was. Methanol (20 mL, 494 mmol) and dichloromethane (3.5 mL, 55 mmol) were placed in a reaction vessel and mixed with stirring. While stirring the reaction solution, oxygen gas was bubbled in at 0.5 L / min at 20°C, and the solution was irradiated with high-energy light including UV-C for 3 hours. Next, the irradiation with high-energy light and the supply of oxygen gas were stopped, and acetic acid (0.57 mL, 10 mmol) was added to the sample solution, followed by stirring at 20° C. for 3 hours. The reaction solution 1 H NMR analysis confirmed the formation of methyl acetate in >99% conversion.

[0088] Example 2: Synthesis of methyl nonanoate [ka] Methanol (30 mL, 741 mmol) and dichloromethane (5.3 mL, 82 mmol) were placed in a reaction vessel similar to that of Example 1 and mixed by stirring. While stirring the reaction solution, oxygen gas was bubbled in at 0.5 L / min at 20°C, and high-energy light containing UV-C was irradiated for 3 hours. Next, the irradiation of high-energy light and the supply of oxygen gas were stopped, and nonanoic acid (8.73 mL, 50 mmol) was added to the sample solution, which was then stirred at 50°C for 4 hours. The reaction solution 1 H NMR analysis confirmed the formation of methyl nonanoate in >99% conversion.

[0089] Example 3: Synthesis of 2,2,2-trifluoroethyl acetate [ka] 2,2,2-trifluoroethanol (10 mL, 139 mmol) and dichloromethane (0.96 mL, 15 mmol) were placed in a reaction vessel similar to that of Example 1 and mixed by stirring. While stirring the reaction solution, oxygen gas was bubbled in at 0.5 L / min at 20°C, and high-energy light containing UV-C was irradiated for 3 hours. Next, the irradiation of high-energy light and the supply of oxygen gas were stopped, and acetic acid (0.57 mL, 10 mmol) was added to the sample solution, which was then stirred at 50°C for 6 days. The reaction solution 1 Analysis by 1 H NMR confirmed that 2,2,2-trifluoroethyl acetate was produced in 89% conversion.

[0090] Example 4: Synthesis of 2,2,3,3-tetrafluoro-1-propyl acetate [ka] 2,2,3,3-Tetrafluoro-1-propanol (10 mL, 112 mmol) and dichloromethane (0.8 mL, 12 mmol) were placed in a reaction vessel similar to that of Example 1 and mixed by stirring. While stirring the reaction solution, oxygen gas was bubbled in at 0.5 L / min at 20°C, and high-energy light containing UV-C was irradiated for 3 hours. Next, the irradiation of high-energy light and the supply of oxygen gas were stopped, and acetic acid (0.57 mL, 10 mmol) was added to the sample solution, which was then stirred at 50°C for 4 days. The reaction solution 1 Analysis by 1 H NMR confirmed the formation of 2,2,3,3-tetrafluoro-1-propyl acetate in 82% conversion.

[0091] Example 5: Synthesis of methyl isobutyrate [ka] Methanol (20 mL, 494 mmol) and dichloromethane (3.5 mL, 55 mmol) were placed in a reaction vessel similar to that of Example 1 and mixed by stirring. While stirring the reaction solution, oxygen gas was bubbled in at 0.5 L / min at 20°C, and high-energy light containing UV-C was irradiated for 3 hours. Next, the irradiation of high-energy light and the supply of oxygen gas were stopped, and isobutyric acid (0.93 mL, 10 mmol) was added to the sample solution, which was then stirred at 50°C for 3 hours. The reaction solution 1 Analysis by 1 H NMR confirmed the formation of methyl isobutyrate in >99% conversion.

[0092] Example 6: Synthesis of methyl acetate [ka] Methanol (20 mL, 494 mmol), dichloromethane (3.5 mL, 55 mmol), and acetic acid (0.57 mL, 10 mmol) were placed in a reaction vessel similar to that used in Example 1 and mixed with stirring. While stirring the reaction solution, oxygen gas was bubbled in at 0.5 L / min at 20°C, and high-energy light including UV-C was irradiated for 5 hours. 1 Analysis by 1 H NMR confirmed the formation of methyl acetate in >99% conversion.

[0093] Example 7: Synthesis of methyl benzoate [ka] Methanol (20 mL, 494 mmol), dichloromethane (3.5 mL, 55 mmol), and benzoic acid (1.22 g, 10 mmol) were placed in a reaction vessel similar to that used in Example 1 and mixed with stirring. While stirring the reaction solution, oxygen gas was bubbled in at 20°C at 0.5 L / min, and the solution was irradiated with high-energy light containing UV-C for 7 hours. Next, the irradiation with high-energy light and the supply of oxygen gas were stopped, and the solution was stirred at 50°C for an additional 3 days. 1 Analysis by 1 H NMR confirmed the formation of methyl benzoate in 43% conversion.

[0094] Example 8: Synthesis of methyl acetate by transesterification method [ka] Methanol (20 mL, 494 mmol), dichloromethane (3.5 mL, 55 mmol), and ethyl acetate (0.98 mL, 10 mmol) were placed in a reaction vessel similar to that used in Example 1 and mixed with stirring. While stirring the reaction solution, oxygen gas was bubbled in at 20°C at 0.5 L / min, and the solution was irradiated with high-energy light including UV-C for 5 hours. Next, the irradiation with high-energy light and the supply of oxygen gas were stopped, and the solution was stirred at 50°C for an additional 2 days. 1 Analysis by 1 H NMR confirmed the formation of methyl acetate in 74% conversion.

[0095] Comparative Example 1: Esterification reaction by heating a mixed solution of alcohol and acetic acid [ka] In a 50 mL eggplant flask, the alcohol (20 mL) and acetic acid (0.57 mL, 10 mmol) shown in Table 1 were placed and stirred at 50° C. for 24 hours. 1 When analyzed by H NMR, the conversion rate to the target acetate ester was as shown in Table 1. As shown in the results in Table 1, it became clear that the esterification reaction does not proceed easily by heating alone without a catalyst.

[0096] [Table 1]

[0097] Comparative Example 2: Esterification reaction by heating a mixed solution of methanol and benzoic acid [ka] Methanol (20 mL, 494 mmol) and benzoic acid (1.22 g, 10 mmol) were placed in a 50 mL eggplant-shaped flask and stirred at 50° C. for 24 hours. 1Analysis by 1 H NMR did not confirm the presence of any product.

[0098] Example 9: Deprotection reaction of BOC-protected amino acid [ka] N-(t-butoxycarbonyl)-L-phenylalanine methyl ester (1.4 g, 5 mmol), dichloromethane (30 mL, 468 mmol), and acetonitrile (10 mL) were placed in a reaction vessel similar to that of Example 1 and mixed with stirring. While stirring the reaction solution, oxygen gas was bubbled in at 25°C at 0.5 L / min, and high-energy light including UV-C was irradiated for 4 hours. Next, n-hexane was added to the reaction solution, and a white precipitate was precipitated. The precipitate was collected by suction filtration and dried in vacuum to obtain L-phenylalanine methyl hydrochloride in an isolated yield of 48%.

[0099] Example 10: Synthesis of dimethyl octafluoroadipate [ka] Methanol (20 mL, 520 mmol) and dichloromethane (3.5 mL, 56 mmol) were placed in a reaction vessel similar to that of Example 1 and mixed with stirring. While stirring the reaction solution, oxygen gas was bubbled in at 0.5 L / min at 20°C, and high-energy light including UV-C was irradiated for 3 hours. Octafluoroadipic acid (22 g, 76 mmol) was then added to the reaction solution, and the solution was stirred at 50°C for 2 days. Dichloromethane and water were added to the reaction solution to separate it, the organic phase was dried over anhydrous sodium sulfate, and the solvent was removed using an evaporator. The resulting residue was 1 Analysis by 1 H NMR confirmed that the target compound, dimethyl octafluoroadipate, was produced (yield >99%).

[0100] Example 11: Synthesis of bis[2-(2-methoxyethoxy)ethyl] adipate [ka] Diethylene glycol monomethyl ether (32.4 mL, 330 mmol) and dichloromethane (3.5 mL, 56 mmol) were placed in a reaction vessel similar to that of Example 1 and mixed by stirring. While stirring the reaction solution, oxygen gas was bubbled in at 0.5 L / min at 20°C, and high-energy light including UV-C was irradiated for 3 hours. Next, adipic acid (1.46 g, 10 mmol) was added to the reaction solution, and the mixture was stirred at 50°C for 2 days. Unreacted diethylene glycol monomethyl ether was removed from the reaction solution by vacuum distillation, and dichloromethane and water were added to the residue to separate the liquids, and the organic phase was dried over anhydrous sodium sulfate, the solvent was removed using an evaporator, and the mixture was further vacuum dried at 100°C. The obtained residue was 1 Analysis by H NMR confirmed that the target compound, bis[2-(2-methoxyethoxy)ethyl]adipate, was produced (yield: 56%).

[0101] Example 12: Synthesis of polyester from 1,4-butanediol and adipic acid [ka] 1,4-butanediol (4.5 mL, 50 mmol) and dichloromethane (0.32 mL, 5.6 mmol) were placed in a reaction vessel similar to that of Example 1 and mixed by stirring. While stirring the reaction solution, oxygen gas was bubbled in at 0.5 L / min at 20°C, and high-energy light including UV-C was irradiated for 3 hours. Next, a solution of adipic acid (7.3 g, 50 mmol) dissolved in acetonitrile (20 mL) was added to the reaction solution, and the solution was stirred at 90°C for 2 days. Dichloromethane and water were added to the reaction solution to separate the liquids, the organic phase was dried over anhydrous sodium sulfate, and the solvent was removed using an evaporator. The resulting pale yellow oil was 1 Analysis by 1 H NMR confirmed that the desired polyester was produced (yield: 64%). The polyester thus obtained was analyzed by HPLC to determine the number average molecular weight Mn (polystyrene standard) and the weight average molecular weight Mw. The results are shown in Table 2.

[0102] [Table 2]

[0103] Example 13: Synthesis of polyester from 1,4-butanediol and adipic acid [ka] Tetraethylene glycol (8.7 mL, 50 mmol) and dichloromethane (0.8 mL, 13 mmol) were placed in a reaction vessel similar to that of Example 1 and mixed by stirring. While stirring the reaction solution, oxygen gas was bubbled in at 0.5 L / min at 20°C, and high-energy light including UV-C was irradiated for 3 hours. Next, a solution of adipic acid (7.3 g, 50 mmol) dissolved in 20 mL of acetonitrile was added to the reaction solution, and the solution was stirred at 90°C for 2 days. Dichloromethane and water were added to the reaction solution to separate it, the organic phase was dried over anhydrous sodium sulfate, and the solvent was removed using an evaporator. The resulting pale yellow oil was 1 Analysis by 1 H NMR confirmed that the desired polyester was formed (yield: 44%). The polyester thus obtained was analyzed by HPLC to determine the number average molecular weight Mn (polystyrene standard) and the weight average molecular weight Mw. The results are shown in Table 3.

[0104] [Table 3]

[0105] Example 14: Acetal protection of cyclohexanone [ka] Ethylene glycol (20 mL, 360 mmol) and dichloromethane (2.5 mL, 40 mmol) were placed in a reaction vessel similar to that of Example 1 and mixed with stirring. While stirring the reaction solution, oxygen gas was bubbled in at 20°C at 0.5 L / min, and high-energy light including UV-C was irradiated for 3 hours. Next, cyclohexanone (1.0 mL, 10 mmol) was added to the reaction solution, and the solution was heated to reflux for 3 hours. 1 H NMR analysis confirmed that the desired 1,4-dioxaspiro[4.5]decane had been produced and that the carbonyl group of cyclohexanone had been protected (>99% conversion). [Explanation of symbols]

[0106] 1: reaction vessel, 2: high energy light irradiation means, 3: water bath, 4: Jacket, 5: Stirrer, 6: Cooling tube

Claims

1. 1. A process for producing an ester compound, comprising: A composition containing dichloromethane, a carboxylic acid compound, and an alcohol compound is subjected to a gas flow containing 15% by volume or more and 100% by volume or less of oxygen or the gas is blown therein by bubbling, and the composition is subjected to a UV-C light having a wavelength of 180 nm or more and an intensity of 1 mW / cm 2 Above, 50mW / cm 2 The method includes a step of decomposing dichloromethane by irradiating the dichloromethane with high-energy light for 0.5 hours or more and 10 hours or less, The combination of the carboxylic acid compound and the alcohol compound is represented by the following carboxylic acid compound (II 1 ) and the following alcohol compound (I 1 ), the following carboxylic acid compound (II 2 ) and the following alcohol compound (I 2 ), or the following carboxylic acid compound (II 1 ) and the following alcohol compound (I 3 ). [Formula 1] [In the formula, R 1 and R 2 each independently represents a C 1-10 monovalent chain aliphatic hydrocarbon group optionally substituted with a substituent α, a C 3-10 monovalent cyclic aliphatic hydrocarbon group optionally substituted with a substituent β, a C 6-15 monovalent aromatic hydrocarbon group optionally substituted with a substituent β, a monovalent organic group to which two or more and five or less of these groups are bonded, or a monovalent organic group represented by the formula R 22 -[-X-R 21 -] r - (X represents O or S, and is preferably O, R 21 represents a C 2-8 alkanediyl group, R 22 represents a C 1-6 alkyl group, and r represents an integer of 1 or more and 180 or less), the substituent α represents one or more substituents selected from a C 1-6 alkoxy group, a halogeno group, an ether group, a thioether group, a carbonyl group, and a tri(C 1-6 alkyl)silyl group; The substituent β represents one or more substituents selected from a C 1-6 alkyl group, a C 1-6 alkoxy group, a halogeno group, an ether group, a thioether group, a carbonyl group, and a tri(C 1-6 alkyl)silyl group. [chemical 2] [In the formula, R 1 and R 2 each independently represents a C 1-10 divalent chain aliphatic hydrocarbon group optionally substituted with a substituent α, a C 3-10 divalent cyclic aliphatic hydrocarbon group optionally substituted with a substituent β, a C 6-15 divalent aromatic hydrocarbon group optionally substituted with a substituent β, a divalent organic group to which two or more and five or less of these groups are bonded, or a divalent organic group represented by the formula -[-X-R 21 -] r - (X represents O or S, and is preferably O, R 21 represents a C 2-8 alkanediyl group, and r represents an integer of 1 or more and 180 or less), the substituent α represents one or more substituents selected from a C 1-6 alkoxy group, a halogeno group, an ether group, a thioether group, a carbonyl group, and a tri(C 1-6 alkyl)silyl group; The substituent β represents one or more substituents selected from a C 1-6 alkyl group, a C 1-6 alkoxy group, a halogeno group, an ether group, a thioether group, a carbonyl group, and a tri(C 1-6 alkyl)silyl group. [C3] [In the formula, R 1 represents a C 1-10 trivalent chain aliphatic hydrocarbon group optionally substituted with a substituent α, a C 3-10 trivalent cyclic aliphatic hydrocarbon group optionally substituted with a substituent β, a C 6-15 trivalent aromatic hydrocarbon group optionally substituted with a substituent β, or a trivalent organic group to which two or more and five or less of these groups are bonded, R 2represents a C 1-10 monovalent chain aliphatic hydrocarbon group optionally substituted with a substituent α, a C 3-10 monovalent cyclic aliphatic hydrocarbon group optionally substituted with a substituent β, a C 6-15 monovalent aromatic hydrocarbon group optionally substituted with a substituent β, a monovalent organic group to which two or more and five or less of these groups are bonded, or a monovalent organic group represented by the formula R 22 -[-X-R 21 -] r - (X represents O or S, and is preferably O, R 21 represents a C 2-8 alkanediyl group, R 22 represents a C 1-6 alkyl group, and r represents an integer of 1 or more and 180 or less), the substituent α represents one or more substituents selected from a C 1-6 alkoxy group, a halogeno group, an ether group, a thioether group, a carbonyl group, and a tri(C 1-6 alkyl)silyl group; The substituent β represents one or more substituents selected from a C 1-6 alkyl group, a C 1-6 alkoxy group, a halogeno group, an ether group, a thioether group, a carbonyl group, and a tri(C 1-6 alkyl)silyl group.

2. 1. A process for producing an ester compound, comprising: A gas containing 15% by volume or more and 100% by volume or less of oxygen is blown into a dichloromethane solution of an alcohol compound under a gas flow or by bubbling the gas, and a UV-C light having a wavelength of 180 nm or more and an intensity of 1 mW / cm is blown into the dichloromethane solution of the alcohol compound. 2 Above, 50mW / cm 2 A step of decomposing dichloromethane by irradiating the dichloromethane with high-energy light for 0.5 hours or more and 10 hours or less as follows: The method includes a step of adding a carboxylic acid compound to the dichloromethane solution containing a decomposition product of dichloromethane to react with the carboxylic acid compound, The combination of the carboxylic acid compound and the alcohol compound is represented by the following carboxylic acid compound (II 1 ) and the following alcohol compound (I 1 ), the following carboxylic acid compound (II 2 ) and the following alcohol compound (I 2 ), or the following carboxylic acid compound (II 1 ) and the following alcohol compound (I 3). [C4] [In the formula, R 1 and R 2 each independently represents a C 1-10 monovalent chain aliphatic hydrocarbon group optionally substituted with a substituent α, a C 3-10 monovalent cyclic aliphatic hydrocarbon group optionally substituted with a substituent β, a C 6-15 monovalent aromatic hydrocarbon group optionally substituted with a substituent β, a monovalent organic group to which two or more and five or less of these groups are bonded, or a monovalent organic group represented by the formula R 22 -[-X-R 21 -] r - (X represents O or S, and is preferably O, R 21 represents a C 2-8 alkanediyl group, R 22 represents a C 1-6 alkyl group, and r represents an integer of 1 or more and 180 or less), the substituent α represents one or more substituents selected from a C 1-6 alkoxy group, a halogeno group, an ether group, a thioether group, a carbonyl group, and a tri(C 1-6 alkyl)silyl group; The substituent β represents one or more substituents selected from a C 1-6 alkyl group, a C 1-6 alkoxy group, a halogeno group, an ether group, a thioether group, a carbonyl group, and a tri(C 1-6 alkyl)silyl group. [C5] [In the formula, R 1 and R 2 each independently represents a C 1-10 divalent chain aliphatic hydrocarbon group optionally substituted with a substituent α, a C 3-10 divalent cyclic aliphatic hydrocarbon group optionally substituted with a substituent β, a C 6-15 divalent aromatic hydrocarbon group optionally substituted with a substituent β, a divalent organic group to which two or more and five or less of these groups are bonded, or a divalent organic group represented by the formula -[-X-R 21 -] r - (X represents O or S, and is preferably O, R 21 represents a C 2-8 alkanediyl group, and r represents an integer of 1 or more and 180 or less), the substituent α represents one or more substituents selected from a C 1-6 alkoxy group, a halogeno group, an ether group, a thioether group, a carbonyl group, and a tri(C 1-6 alkyl)silyl group; The substituent β represents one or more substituents selected from a C 1-6 alkyl group, a C 1-6 alkoxy group, a halogeno group, an ether group, a thioether group, a carbonyl group, and a tri(C 1-6 alkyl)silyl group. [C6] [In the formula, R 1 represents a C 1-10 trivalent chain aliphatic hydrocarbon group optionally substituted with a substituent α, a C 3-10 trivalent cyclic aliphatic hydrocarbon group optionally substituted with a substituent β, a C 6-15 trivalent aromatic hydrocarbon group optionally substituted with a substituent β, or a trivalent organic group to which two or more and five or less of these groups are bonded, R 2 represents a C 1-10 monovalent chain aliphatic hydrocarbon group optionally substituted with a substituent α, a C 3-10 monovalent cyclic aliphatic hydrocarbon group optionally substituted with a substituent β, a C 6-15 monovalent aromatic hydrocarbon group optionally substituted with a substituent β, a monovalent organic group to which two or more and five or less of these groups are bonded, or a monovalent organic group represented by the formula R 22 -[-X-R 21 -] r - (X represents O or S, and is preferably O, R 21 represents a C 2-8 alkanediyl group, R 22 represents a C 1-6 alkyl group, and r represents an integer of 1 or more and 180 or less), the substituent α represents one or more substituents selected from a C 1-6 alkoxy group, a halogeno group, an ether group, a thioether group, a carbonyl group, and a tri(C 1-6 alkyl)silyl group; The substituent β represents one or more substituents selected from a C 1-6 alkyl group, a C 1-6 alkoxy group, a halogeno group, an ether group, a thioether group, a carbonyl group, and a tri(C 1-6 alkyl)silyl group.

3. 1. A process for producing an ester compound, comprising: A dichloromethane solution of a carboxylic acid compound and an alcohol compound is subjected to a gas flow containing 15% by volume or more and 100% by volume of oxygen or the gas is blown therein by bubbling, and the gas is irradiated with UV-C having a wavelength of 180 nm or more and an intensity of 1 mW / cm 2 Above, 50mW / cm 2 The method includes a step of decomposing dichloromethane by irradiating the dichloromethane with high-energy light for 0.5 hours or more and 10 hours or less, The combination of the carboxylic acid compound and the alcohol compound is represented by the following carboxylic acid compound (II 1 ) and the following alcohol compound (I 1 ), the following carboxylic acid compound (II 2 ) and the following alcohol compound (I 2 ), or the following carboxylic acid compound (II 1 ) and the following alcohol compound (I 3 ). [C7] [In the formula, R 1 and R 2 each independently represents a C 1-10 monovalent chain aliphatic hydrocarbon group optionally substituted with a substituent α, a C 3-10 monovalent cyclic aliphatic hydrocarbon group optionally substituted with a substituent β, a C 6-15 monovalent aromatic hydrocarbon group optionally substituted with a substituent β, a monovalent organic group to which two or more and five or less of these groups are bonded, or a monovalent organic group represented by the formula R 22 -[-X-R 21 -] r - (X represents O or S, and is preferably O, R 21 represents a C 2-8 alkanediyl group, R 22 represents a C 1-6 alkyl group, and r represents an integer of 1 or more and 180 or less), the substituent α represents one or more substituents selected from a C 1-6 alkoxy group, a halogeno group, an ether group, a thioether group, a carbonyl group, and a tri(C 1-6 alkyl)silyl group; The substituent β represents one or more substituents selected from a C 1-6 alkyl group, a C 1-6 alkoxy group, a halogeno group, an ether group, a thioether group, a carbonyl group, and a tri(C 1-6 alkyl)silyl group. [C8] [In the formula, R 1 and R 2each independently represents a C 1-10 divalent chain aliphatic hydrocarbon group optionally substituted with a substituent α, a C 3-10 divalent cyclic aliphatic hydrocarbon group optionally substituted with a substituent β, a C 6-15 divalent aromatic hydrocarbon group optionally substituted with a substituent β, a divalent organic group to which two or more and five or less of these groups are bonded, or a divalent organic group represented by the formula -[-X-R 21 -] r - (X represents O or S, and is preferably O, R 21 represents a C 2-8 alkanediyl group, and r represents an integer of 1 or more and 180 or less), the substituent α represents one or more substituents selected from a C 1-6 alkoxy group, a halogeno group, an ether group, a thioether group, a carbonyl group, and a tri(C 1-6 alkyl)silyl group; The substituent β represents one or more substituents selected from a C 1-6 alkyl group, a C 1-6 alkoxy group, a halogeno group, an ether group, a thioether group, a carbonyl group, and a tri(C 1-6 alkyl)silyl group. [C9] [In the formula, R 1 represents a C 1-10 trivalent chain aliphatic hydrocarbon group optionally substituted with a substituent α, a C 3-10 trivalent cyclic aliphatic hydrocarbon group optionally substituted with a substituent β, a C 6-15 trivalent aromatic hydrocarbon group optionally substituted with a substituent β, or a trivalent organic group to which two or more and five or less of these groups are bonded, R 2 represents a C 1-10 monovalent chain aliphatic hydrocarbon group optionally substituted with a substituent α, a C 3-10 monovalent cyclic aliphatic hydrocarbon group optionally substituted with a substituent β, a C 6-15 monovalent aromatic hydrocarbon group optionally substituted with a substituent β, a monovalent organic group to which two or more and five or less of these groups are bonded, or a monovalent organic group represented by the formula R 22 -[-X-R 21 -] r - (X represents O or S, and is preferably O, R 21 represents a C 2-8 alkanediyl group, R 22 represents a C 1-6 alkyl group, and r represents an integer of 1 or more and 180 or less), the substituent α represents one or more substituents selected from a C 1-6 alkoxy group, a halogeno group, an ether group, a thioether group, a carbonyl group, and a tri(C 1-6 alkyl)silyl group; The substituent β represents one or more substituents selected from a C 1-6 alkyl group, a C 1-6 alkoxy group, a halogeno group, an ether group, a thioether group, a carbonyl group, and a tri(C 1-6 alkyl)silyl group.

4. 1. A process for producing an ester compound, comprising: the ester compound is an ester compound of a carboxylic acid and an alcohol A, A composition containing dichloromethane, an ester compound of an alcohol B different from the alcohol A, and the alcohol A is subjected to a gas flow containing 15% by volume or more and 100% by volume or less of oxygen or the gas is blown therein by bubbling, and the composition is subjected to a UV-C irradiation having a wavelength of 180 nm or more and an intensity of 1 mW / cm 2 Above, 50mW / cm 2 The method includes a step of decomposing dichloromethane by irradiating the dichloromethane with high-energy light for 0.5 hours or more and 10 hours or less, The combination of the ester compound of the alcohol B and the alcohol A is the following p-valent ester compound (III 1 ) and the following monohydric alcohol compound (IV 1 ), or the following monovalent ester compound (III 2 ) and the following q-valent alcohol compound (IV 2 ). [C10] [In the formula, R 3 represents a C 1-10 p-valent chain aliphatic hydrocarbon group which may be substituted with a substituent α, a C 3-10 p-valent cyclic aliphatic hydrocarbon group which may be substituted with a substituent β, a C 6-15 p-valent aromatic hydrocarbon group which may be substituted with a substituent β, or a p-valent organic group to which two or more and five or less of these groups are bonded; R 4 ~R 7each independently represents a C 1-10 monovalent chain aliphatic hydrocarbon group optionally substituted with a substituent α, a C 3-10 monovalent cyclic aliphatic hydrocarbon group optionally substituted with a substituent β, a C 6-15 monovalent aromatic hydrocarbon group optionally substituted with a substituent β, a monovalent organic group to which two or more and five or less of these groups are bonded, or a monovalent organic group represented by the formula R 22 -[-X-R 21 -] r - (X represents O or S, and is preferably O, R 21 represents a C 2-8 alkanediyl group, R 22 represents a C 1-6 alkyl group, and r represents an integer of 1 or more and 180 or less), R 8 represents a C 1-10 q-valent chain aliphatic hydrocarbon group optionally substituted with a substituent α, a C 3-10 q-valent cyclic aliphatic hydrocarbon group optionally substituted with a substituent β, a C 6-15 q-valent aromatic hydrocarbon group optionally substituted with a substituent β, or a q-valent organic group to which two or more and five or less of these groups are bonded; the substituent α represents one or more substituents selected from a C 1-6 alkoxy group, a halogeno group, an ether group, a thioether group, a carbonyl group, and a tri(C 1-6 alkyl)silyl group; the substituent β represents one or more substituents selected from a C 1-6 alkyl group, a C 1-6 alkoxy group, a halogeno group, an ether group, a thioether group, a carbonyl group, and a tri(C 1-6 alkyl)silyl group; p represents an integer of 1 to 5, q represents an integer of 1 to 5, However, R 4 and R 5 are not the same organic group, R 7 and R 8 are not the same organic group.

5. 1. A process for producing an acetal compound, comprising: A composition containing dichloromethane and an alcohol compound is subjected to a gas flow containing 15% by volume or more and 100% by volume or less of oxygen or the gas is blown therein by bubbling, and the composition is subjected to a UV-C irradiation having a wavelength of 180 nm or more and an intensity of 1 mW / cm 2 Above, 50mW / cm 2 A step of decomposing dichloromethane by irradiating the dichloromethane with high-energy light for 0.5 hours or more and 10 hours or less as follows: The method includes a step of reacting a carbonyl compound in the presence of a decomposition product of dichloromethane, The method is characterized in that the combination of the carbonyl compound and the alcohol compound is the following carbonyl compound (VI) and the following alcohol compound (VII), or the following carbonyl compound (VI) and the following 1,2-ethanediol or 1,3-propanediol. [C11] [In the formula, R 9 ~R 11 each independently represents a C 1-10 monovalent chain aliphatic hydrocarbon group optionally substituted with a substituent α, a C 3-10 monovalent cyclic aliphatic hydrocarbon group optionally substituted with a substituent β, a C 6-15 monovalent aromatic hydrocarbon group optionally substituted with a substituent β, a monovalent organic group to which two or more and five or less of these groups are bonded, or a monovalent organic group represented by the formula R 22 -[-X-R 21 -] r - (X represents O or S, and is preferably O, R 21 represents a C 2-8 alkanediyl group, R 22 represents a C 1-6 alkyl group, and r represents an integer of 1 or more and 180 or less), the substituent α represents one or more substituents selected from a C 1-6 alkoxy group, a halogeno group, an ether group, a thioether group, a carbonyl group, and a tri(C 1-6 alkyl)silyl group; the substituent β represents one or more substituents selected from a C 1-6 alkyl group, a C 1-6 alkoxy group, a halogeno group, an ether group, a thioether group, a carbonyl group, and a tri(C 1-6 alkyl)silyl group; t represents 2 or 3.

6. A method for deprotecting a compound having an amino group and / or a hydroxyl group protected by a Boc group by cleaving the Boc group, comprising the steps of: A composition containing dichloromethane and the compound having an amino group protected by a Boc group is subjected to a gas flow containing 15% by volume or more and 100% by volume of oxygen or the gas is blown therein by bubbling, and the composition is subjected to a UV-C irradiation having a wavelength of 180 nm or more and an intensity of 1 mW / cm 2 Above, 50mW / cm 2 The method includes a step of decomposing dichloromethane by irradiating the dichloromethane with high-energy light for 0.5 hours or more and 10 hours or less, The method, wherein the compound having an amino group and / or a hydroxyl group protected by a Boc group is the following compound (IX), compound (XI) or compound (XIII): [C12] [In the formula, R 12 and R 13 each independently represents a C 1-10 monovalent chain aliphatic hydrocarbon group optionally substituted with a substituent α, a C 3-10 monovalent cyclic aliphatic hydrocarbon group optionally substituted with a substituent β, a C 6-15 monovalent aromatic hydrocarbon group optionally substituted with a substituent β, a monovalent organic group to which two or more and five or less of these groups are bonded, or a monovalent organic group represented by the formula R 22 -[-X-R 21 -] r - (X represents O or S, and is preferably O, R 21 represents a C 2-8 alkanediyl group, R 22 represents a C 1-6 alkyl group, and r represents an integer of 1 or more and 180 or less), the substituent α represents one or more substituents selected from a C 1-6 alkoxy group, a halogeno group, an ether group, a thioether group, a carbonyl group, and a tri(C 1-6 alkyl)silyl group; the substituent β represents one or more substituents selected from a C 1-6 alkyl group, a C 1-6 alkoxy group, a halogeno group, an ether group, a thioether group, a carbonyl group, and a tri(C 1-6 alkyl)silyl group; R 14 indicates an amino acid side chain group, R 15 , OH, OR 16 (In the formula, R 16represents a protecting group for a carboxy group or a carrier), or —[—NH—CHR 17 -C(=O)-] s -R 18 (In the formula, R 17 indicates an amino acid side chain, R 18 is OH or OR 19 (In the formula, R 19 represents a protecting group for a carboxy group or a carrier), s represents an integer of 1 or more, and when s is an integer of 2 or more, a plurality of R 17 may be the same or different).

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