Photoreaction product manufacturing method and manufacturing device

Abstract

Photoreaction products are efficiently produced by flow synthesis using a simple device. [Solution] A photoreaction product is produced by flow synthesis through a reaction process in which a reactant solution containing raw materials is irradiated with light while flowing through a reaction flow path to obtain a reaction solution containing the photoreaction product and unreacted raw materials, and a circulation process in which the reaction solution is returned to the reaction flow path as a new reactant solution and circulated, thereby repeating the reaction process. In the reaction process, the flow rate of the reactant solution may be 50 mm / sec or more in linear velocity. The raw material concentration in the reactant solution may be 100 mM or less. The raw material concentration of a first reactant solution containing starting materials may be 100 mM or less, and new raw materials may be added after the start of the reaction so that the concentration of unreacted raw materials in the reaction solution does not exceed 100 mM. The photoreaction product may be a cyclic compound.

Description

[Technical Field]

[0001] The present invention relates to a method and an apparatus for producing a photoreaction product by flow synthesis. [Background technology]

[0002] Photoreactions (photochemical reactions) are generally conducted using a batch reactor-type photoreactor, which allows the target product to be obtained by irradiating light onto raw materials contained in a flask or other reactor. However, this device has problems such as a decrease in reaction efficiency as the concentration of the reaction solution increases, and a large reactor makes it difficult to irradiate light evenly, and requires a large light source, resulting in low reaction efficiency and energy efficiency.

[0003] Therefore, in order to solve the problems of such batch reactor-type photoreactors, a flow synthesis method using a flow-type photoreactor has been proposed. Specifically, in flow synthesis, the target product is obtained by photoreacting raw materials by irradiating them with light while continuously flowing them through a reaction tube (reaction flow path).

[0004] As an example of such a flow-type photoreaction device, Japanese Patent Laid-Open Publication No. 2007-75682 (Patent Document 1) discloses a flow-type photochemical reaction device comprising a reaction section formed by a light-transmitting flow path, a liquid delivery section for delivering a reactant to the reaction section, a light source section having at least one light source for irradiating the reaction section to cause a photochemical reaction in the reactant in the light-transmitting flow path, and a recovery section for recovering a photochemical reaction product resulting from the photochemical reaction, wherein the reaction section is unitized as a single unit and is detachably attached to the light source section so as to be integral with the light source section. The reaction section is described as comprising a light-transmitting cylindrical body and a light-transmitting tube wound around the outer peripheral surface of the cylindrical body to form a light-transmitting flow path, and the light source section is disposed inside the cylindrical body so as to irradiate the tube from the inner peripheral surface of the cylindrical body through the cylindrical body. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] Japanese Patent Application Laid-Open No. 2007-75682 Summary of the Invention [Problem to be solved by the invention]

[0006] The flow-type photoreactor of Patent Document 1 has improved reaction efficiency and energy efficiency compared to a batch reactor-type photoreactor. However, even with the reactor of Patent Document 1, the reaction efficiency is still insufficient, and in order to improve the yield or shorten the reaction time, it is necessary to increase the size of the reactor, for example, by increasing the length of the flow path.

[0007] Therefore, an object of the present invention is to provide a method for efficiently producing a photoreaction product with high productivity by flow synthesis using a simple apparatus.

[0008] Another object of the present invention is to provide a method for producing a photocyclized product in a short time and in a high yield by flow synthesis using a simple apparatus. [Means for solving the problem]

[0009] As a result of extensive research to achieve the above object, the present inventors have discovered that in flow synthesis, a photoreaction product can be efficiently produced by flow synthesis using a simple device by circulating a reactant solution containing raw materials and subjecting it to photoreaction multiple times, and have completed the present invention.

[0010] That is, the present invention includes the following aspects.

[0011] Aspect [1]: A method for producing a photoreaction product by flow synthesis, a reaction step of irradiating a reactant solution containing raw materials with light while the reactant solution is flowing through a reaction flow channel to obtain a reaction solution containing the photoreaction product and unreacted raw materials; and a circulation step for circulating the reaction liquid back into the reaction flow path as a new reactant liquid, thereby repeating the reaction step.

[0012] Aspect [2]: The production method according to aspect [1], wherein in the reaction step, the flow velocity of the reactant liquid is 50 mm / sec or more in linear velocity.

[0013] Aspect [3]: The method according to aspect [1] or [2], wherein the raw material concentration in the reaction solution is 100 mM or less.

[0014] Aspect [4]: ​​A manufacturing method according to any one of Aspects [1] to [3], wherein the raw material concentration of the first reactant solution containing the starting material is 100 mM or less, and after the start of the reaction, new raw materials are added so that the concentration of unreacted raw materials in the reaction solution does not exceed 100 mM.

[0015] Aspect [5]: The production method according to any one of Aspects [1] to [4], further comprising a purification step of purifying the reaction solution.

[0016] Aspect [6]: The method according to any one of Aspects [1] to [5], wherein the reaction liquid purified in the purification step is returned to the reaction flow path as a new liquid to be reacted.

[0017] Aspect [7]: The method according to any one of Aspects [1] to [6], wherein the photoreaction product is a cyclic compound.

[0018] Aspect [8]: The method according to any one of Aspects [1] to [7], wherein the photoreaction product is a fused polycyclic compound.

[0019] Aspect [9]: A manufacturing apparatus for producing a photoreaction product by flow synthesis, a reaction unit including a light source and a reaction flow path, and configured to irradiate a reaction solution containing raw materials with light while the reaction solution flows through the reaction flow path, thereby obtaining a reaction solution containing the photoreaction product and unreacted raw materials; a circulation line for circulating the reaction liquid back into the reaction flow path as a new reactant liquid to repeat the reaction in the reaction unit; and a liquid delivery means for circulating the reactant liquid.

[0020] Aspect

[10] : The manufacturing apparatus according to aspect [9], wherein in the reaction unit, the reaction flow path is wound spirally around the outer periphery of the light source unit.

[0021] In this specification and claims, the reactant liquid is classified into a first reactant liquid containing starting materials (the reactant liquid that is first subjected to the reaction process), a second reactant liquid containing unreacted materials and photoreaction products (a reaction liquid that has undergone a reaction process and is subjected to the reaction process again), and a third reactant liquid containing unreacted materials, additional materials, and photoreaction products (a reaction liquid that has undergone a reaction process and is further supplemented with new materials and is subjected to the reaction process again), and the term is used to include all of these reactant liquids. [Effects of the Invention]

[0022] In the production method of the present invention, in flow synthesis, the reactant solution containing the raw materials is circulated and subjected to the photoreaction multiple times, so that the photoreaction product can be efficiently produced by flow synthesis using a simple device, and for example, the photoreaction product can be obtained in high yield in a short time. [Brief explanation of the drawings]

[0023] [Figure 1] FIG. 1 is a schematic diagram illustrating an example of an apparatus for producing a photoreaction product according to the present invention. DETAILED DESCRIPTION OF THE INVENTION

[0024] The method for producing a photoreaction product of the present invention includes a reaction step in which a reactant liquid containing at least raw materials is irradiated with light while flowing as a reaction target to obtain a reaction liquid containing a photoreaction product and unreacted raw materials, and a circulation step in which the reaction liquid is re-submitted to the reaction step as a reaction target.

[0025] [Photoreaction products] In the production method of the present invention, a photoreaction product is produced by a photoreaction. Examples of types of photoreaction include a photocyclization reaction, a cis-trans isomerization reaction, a photo-Fries rearrangement reaction, and a photo-Barton reaction. Among these photoreactions, a photocyclization reaction is preferred because the reaction product is highly stable and the yield can be easily improved by repeated photoirradiation.

[0026] (raw materials) The raw material may be a solid raw material or a liquid raw material depending on the type of the target photoreaction product.

[0027] Furthermore, the raw material is not particularly limited as long as it is a compound that can be a substrate for photoreaction, and can be appropriately selected from known photocyclizable compounds depending on the type of the target photoreaction product.For example, in the photocyclization reaction, the raw material for the target photocyclized product can be a raw material that is easily cyclized by light irradiation, such as a raw material having an ethylenically unsaturated bond, a sulfur atom, an oxygen atom, a nitrogen atom, etc.Among these, the raw material for the photocyclized product that is the reaction product in the photocyclization reaction is particularly preferably a raw material having an ethylenically unsaturated bond or a thioether bond.

[0028] Among the raw materials for the photocyclization product, examples of the raw material having an ethylenically unsaturated bond, an aromatic ring, or a thioether bond include compounds represented by the following formula (1).

[0029] [ka]

[0030] (In the formula, Ring Z 1 , ring Z 2 and ring Z 3 each independently represents an aliphatic hydrocarbon ring, an aromatic hydrocarbon ring, a heteroaromatic non-aromatic ring, or a heteroaromatic ring; R 1 , R 2 and R 3 each independently represents a substituent, m1, m2, and m3 independently represent an integer of 0 or more, X 1 and X 2 are independently a substituent R 4 a vinylene group which may have a substituent R 5 represents an arylene group or a sulfur atom which may have (n is an integer of 0 or 1 or greater)

[0031] In the formula (1), ring Z 1 , ring Z 2 and ring Z 3 Examples of the aliphatic hydrocarbon ring represented by the formula (I) include cyclo C rings such as cyclohexane ring and cyclodecane ring. 5-10 Alkane rings; bicycloalkane rings such as decalin ring, norbornane ring, tricyclodecane ring (adamantane ring, etc.); cyclo C such as cyclohexene ring 5-10 alkene rings; bicycloalkene rings or tricycloalkene rings such as norbornene rings, etc. These aliphatic hydrocarbon rings can be used alone or in combination of two or more.

[0032] Ring Z 1 , ring Z 2 and ring Z 3 Examples of the aromatic hydrocarbon ring represented by the formula (I) include monocyclic arene rings such as a benzene ring; condensed polycyclic C rings such as a naphthalene ring, an indene ring, an anthracene ring, and a phenanthrene ring; 10-20 arene rings, such as biphenyl ring, phenylnaphthalene ring, binaphthyl ring, terphenyl ring, and other bi- or terarene rings. These aromatic hydrocarbon rings can be used alone or in combination.

[0033] Ring Z 1 , ring Z 2 and ring Z 3Examples of the heterocyclic non-aromatic ring represented by the formula (I) include nitrogen-containing monocyclic heterocyclic non-aromatic rings such as pyrrolidine ring, imidazoline ring, and piperidine ring; oxygen-containing monocyclic heterocyclic non-aromatic rings such as oxolane ring, dioxolane ring, dioxole ring, tetrahydropyran ring, dioxane ring, and dioxine ring; nitrogen- and oxygen-containing monocyclic heterocyclic non-aromatic rings such as morpholine ring; sulfur-containing monocyclic heterocyclic non-aromatic rings such as dithiolane ring; and nitrogen- and sulfur-containing monocyclic heterocyclic non-aromatic rings such as thiadiazoline ring and thiadiazine ring. These heterocyclic non-aromatic rings can be used alone or in combination of two or more.

[0034] Ring Z 1 , ring Z 2 and ring Z 3 Examples of the heteroaromatic ring represented by the formula (I) include nitrogen-containing monocyclic heteroaromatic rings such as pyrrole ring, imidazole ring, triazole ring, pyrazole ring, pyridine ring, pyrazine ring, and triazine ring; nitrogen-containing fused polycyclic heteroaromatic rings such as pyrimidine ring, pyridazine ring, purine ring, indole ring, isoindole ring, benzimidazole ring, quinoline ring, isoquinoline ring, quinoxaline ring, carbazole ring, phenanthridine ring, acridine ring, and phenanthroline ring; nitrogen-containing polycyclic heteroaromatic rings such as tetrazole ring; oxygen-containing monocyclic heteroaromatic rings such as furan ring and pyran ring; chromene ring, isochrome ring, and the like. Examples of heteroaromatic rings include oxygen-containing fused polycyclic heteroaromatic rings such as a thiophene ring and a xanthene ring; sulfur-containing monocyclic heteroaromatic rings such as a thiophene ring and a thiopyran ring; sulfur-containing fused polycyclic heteroaromatic rings such as a benzothiophene ring, an alkylenedioxythiophene ring and a thianthrene ring; nitrogen- and sulfur-containing monocyclic heteroaromatic rings such as a thiazole ring, a thiadiazole ring, a thiazine ring and a thiadiazine ring; nitrogen- and oxygen-containing monocyclic heteroaromatic rings such as an oxazole ring and a furazan ring; nitrogen- and sulfur-containing fused polycyclic heteroaromatic rings such as a phenothiazine ring; and nitrogen- and oxygen-containing fused polycyclic heteroaromatic rings such as a phenoxazine ring. These heteroaromatic rings can be used alone or in combination.

[0035] Ring Z 1 , ring Z 2 and ring Z 3Among these, aromatic hydrocarbon rings and heteroaromatic rings are preferred from the viewpoint of improving the yield of the photocyclization product, and monocyclic arene rings such as benzene rings and fused polycyclic C rings such as naphthalene rings are also preferred. 10-20 Sulfur-containing monocyclic heteroaromatic rings such as an arene ring or a thiophene ring, and sulfur-containing fused polycyclic heteroaromatic rings such as a benzothiophene ring are more preferred, with a benzene ring, a naphthalene ring, and a thiophene ring being even more preferred, and a thiophene ring being the most preferred from the viewpoints of high reactivity and high stability after photocyclization.

[0036] R 1 , R 2 and R 3 Examples of the substituent represented by the formula (I) include a halogen atom, a hydrocarbon group, an alkoxy group, an acyl group, a nitro group, a cyano group, and a substituted amino group.

[0037] Examples of halogen atoms include fluorine atoms, chlorine atoms, bromine atoms, and iodine atoms.

[0038] Examples of the hydrocarbon group include alkyl groups (e.g., C groups such as methyl, ethyl, propyl, isopropyl, n-butyl, and t-butyl groups). 1-10 alkyl groups, cycloalkyl groups (e.g., cyclopentyl groups, cyclohexyl groups, etc.) 5-10 cycloalkyl groups, aryl groups [e.g., phenyl groups, biphenylyl groups, naphthyl groups, etc.] 6-12 Aryl groups; mono- or tri-C such as methylphenyl (or tolyl), dimethylphenyl (or xylyl) groups 1-4 alkyl-phenyl group, etc.], aralkyl group (e.g., benzyl group, phenethyl group, etc.) 6-10 Aryl-C 1-4 alkyl groups, etc.

[0039] Examples of alkoxy groups include C groups such as methoxy, ethoxy, propoxy, n-butoxy, and t-butoxy. 1-10 Examples include alkoxy groups.

[0040] Acyl groups include C groups such as acetyl groups. 1-6 Examples include alkyl-carbonyl groups.

[0041] The substituted amino group may be a mono- or di-C group such as a monomethylamino group or a dimethylamino group. 1-4 Alkylamino group; mono- or bis(C) such as monoacetylamino group, diacetylamino group 1-4 alkyl-carbonyl)amino groups.

[0042] These substituents may be used alone or in combination. 1 , substituent R 2 and substituent R 3 may be different from each other or may be the same. Among these substituents, C 1-6 C such as alkyl group and methoxy group 1-4 Alkoxy groups are preferred.

[0043] The substitution numbers m1, m2 and m3 are 1 , ring Z 2 and ring Z 3 can be appropriately selected depending on the type of each, and is, for example, an integer of 0 to 6, preferably an integer of 0 to 3, further preferably an integer of 0 to 2, more preferably 0 or 1, and most preferably 0.

[0044] When the numbers of substitutions m1, m2 and m3 are each an integer of 2 or more, two or more substituents R 1 , substituent R 2 and substituent R 3 may be different from each other or may be the same.

[0045] X 1 and X 2 Examples of the arylene group represented by the formula (I) include a 1,2-phenylene group, a 1,2-naphthylene group, a 2,3-naphthylene group, a 2,3-biphenylene group, a 3,4-biphenylene group, etc. Of these, a 1,2-phenylene group is preferred.

[0046] X as a linking group 1 is X 2 may be different from, but are preferably the same.

[0047] R which the vinylene group may have 4 The substituent represented by the formula 1 and R 2 The substituents R may be used singly or in combination of two or more. 4 When is an integer of 2 or more, the two or more substituents may be different or the same. 1-6 Alkyl groups are preferred, most preferably unsubstituted.

[0048] R which the arylene group may have 5 The substituent represented by the formula 1 and R 2 The substituents R may be used singly or in combination of two or more. 5 When is an integer of 2 or more, the two or more substituents may be different or the same. 1-6 Alkyl groups are preferred.

[0049] Ring Z 2 and linking group X 2 The repeating number n of the unit combining and may be an integer of 0 or 1 or more, preferably 0 or an integer of 1 to 3, further preferably 0 or an integer of 1 to 2, more preferably 0 or 1, and most preferably 0. When n is 2 or more, 2 or more Z 2 , R 2 and m2 may be different from each other or may be the same.

[0050] In the formula (1), the linking group X 1 and X 2As the alkyl group, a vinylene group which may have a substituent is preferred, and a vinylene group is most preferred, because it has high reactivity and high stability after photocyclization.

[0051] Examples of the compound represented by the formula (1) include 1,2-bis(thiophen-2-yl)ethene, stilbene, dimethylstilbene, dibromostilbene, and 1-(4-bromophenyl)-2-(thiophen-2-yl)ethene. 1 is a vinylene group and n is 0; X such as 1,2-bis(thiophen-2-yl)benzene 1 is a phenylene group and n is 0; compounds in which X is a phenylene group and n is 0; compounds in which X is a phenylene group and n is 0; 1 is a sulfur atom and n is 0.

[0052] (oxidizing agent) The photoreaction can use a conventional catalyst depending on the type of photoreaction, but the photocyclization reaction is preferably carried out in the presence of an oxidizing agent, which may be an inorganic or organic oxidizing agent.

[0053] Examples of inorganic oxidizing agents include oxygen, ozone, air, halogens (e.g., chlorine, bromine, iodine, etc.), halogen compounds (e.g., metal halide salts such as potassium iodide and iron chloride, etc.), manganese compounds (e.g., manganese oxide; permanganic acids such as potassium permanganate, etc.), inorganic peroxides (e.g., hydrogen peroxide; metal peroxides such as sodium peroxide, barium peroxide, and magnesium peroxide; persulfates such as sodium persulfate, potassium persulfate, and ammonium persulfate, etc.), inorganic acids or salts thereof (e.g., chromic acid, potassium chromate, nitric acid, sodium nitrate, sodium hypochlorite, and sodium metaperiodate, etc.), and metal oxides (e.g., ruthenium oxide and osmium oxide, etc.). These inorganic oxidizing agents can be used alone or in combination.

[0054] Examples of organic oxidizing agents include quinones [dichlorodicyanobenzoquinones such as 2,3,5,6-tetrachloro-p-benzoquinone (chloranil), 2-chloro-5-cyano-p-benzoquinone, 2-chloro-6-cyano-p-benzoquinone, 2,3-dichloro-5-cyano-p-benzoquinone, and 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ)]; 2-chloro-3-cyano-1,4-naphthoquinone, 2-chloro-5-cyano-1,4-naphthoquinone, and 2-chloro-3,5-dicyano- 1,4-naphthoquinone, 2-chloro-3,8-dicyano-1,4-naphthoquinone, 2-bromo-3-cyano-1,4-naphthoquinone, etc.), peracids (performic acid, peracetic acid, perpropionic acid, perbenzoic acid, etc.), peresters (e.g., t-butyl hydroperoxide, cumene hydroperoxide, t-butyl peracetate, etc.), dialkyl peroxides (e.g., di-t-butyl peroxide, etc.), diacyl peroxides (e.g., lauroyl peroxide, benzoyl peroxide, etc.), etc. These organic oxidizing agents can be used alone or in combination of two or more.

[0055] Among these oxidizing agents, halogens such as iodine and bromine, halogen compounds, and quinones are preferred from the viewpoint of improving the yield of the photocyclized product, oxygen, iodine, metal iodide salts such as potassium iodide, metal halides such as iron chloride, and quinones such as chloranil and DDQ are more preferred, and iodine is even more preferred.

[0056] The proportion of the oxidizing agent may be 0.001 mol or more per mol of the raw materials, for example, 0.001 to 10 mol, preferably 0.005 to 5 mol, and more preferably 0.01 to 3 mol. In particular, when an acid scavenger (described later) is not used in the photoreaction, the proportion of the oxidizing agent per mol of the raw materials is, for example, 0.001 to 1 mol, preferably 0.005 to 0.5 mol, more preferably 0.01 to 0.3 mol, more preferably 0.03 to 0.2 mol, and most preferably 0.05 to 0.15 mol. On the other hand, when an acid scavenger (described later) is used in the photoreaction, the proportion of the oxidizing agent per mol of the raw materials is, for example, 0.1 to 10 mol, preferably 0.5 to 8 mol, more preferably 1 to 5 mol, more preferably 1.1 to 3 mol, and most preferably 1.2 to 2.5 mol. If the proportion of the oxidizing agent is too low, the effect of promoting the photocyclization reaction may be reduced, while if the proportion is too high, the raw materials may not be sufficiently irradiated with light, resulting in a reduced photocyclization reaction.

[0057] (acid scavenger) When an oxidizing agent is used in the photoreaction, an acid scavenger may be used to capture the generated acid (e.g., hydrogen iodide, etc.). Conventional acid scavengers can be used as the acid scavenger, and examples thereof include amine compounds, epoxy compounds, carbodiimide compounds, and oxazoline compounds. These acid scavengers can be used alone or in combination. Among these acid scavengers, amine compounds and epoxy compounds are preferred.

[0058] Examples of the amine compound include aliphatic amines (e.g., alkylamines such as ethylamine, propylamine, isobutylamine, diethylamine, isobutylamine, and triethylamine), aromatic amines (e.g., aniline; N-alkylanilines such as N-methylaniline; N,N-dialkylanilines such as N,N-dimethylaniline and N,N-diethylaniline), heterocyclic amines {e.g., pyrrolidines such as pyrrolidine, 1-methylpyrrolidine, and 1-ethylpyrrolidine; pyridine, collidine, lutidine, 4-(dimethylamino)pyridine, 4- Examples of suitable amine compounds include pyridines such as pyrrolidinopyridine, quinoline, imidazoles such as imidazole, 2-methylimidazole, and 2-ethyl-4-methylimidazole, morpholines such as morpholine, 4-methylmorpholine, and 4-ethylmorpholine, piperidines such as piperidine, 1-methylpiperidine, 1-ethylpiperidine, 2,6-dimethylpiperazine, and 1,2,2',6,6'-pentamethylpiperidine, triethylenediamine, 1,5-diazabicyclo[4.3.0]-5-nonene, and 1,8-diazabicyclo[5.4.0]-7-undecene. These amine compounds can be used alone or in combination.

[0059] Examples of epoxy compounds include oxirane compounds [e.g., alkyloxirane compounds such as ethylene oxide, propylene oxide, butylene oxide (1,2-epoxybutane, 2,3-epoxybutane, etc.), pentylene oxide (1,2-epoxypentane, etc.), and hexylene oxide (1,2-epoxyhexane, etc.); aryloxysilane compounds such as 1,2-epoxystyrene and alkyl-1,2-epoxystyrene, etc.]; glycidyl ether compounds (e.g., alkyl glycidyl ethers such as methyl glycidyl ether and ethyl glycidyl ether; aryl glycidyl ethers such as phenyl glycidyl ether and naphthyl glycidyl ether, etc.); alkylene or polyalkylene glycol diglycidyl ethers such as ethylene glycol diglycidyl ether, triethylene glycol diglycidyl ether, and butanediol diglycidyl ether), glycidyl ester compounds (for example, aliphatic glycidyl esters such as glycidyl acrylate and glycidyl methacrylate; alicyclic glycidyl esters such as diglycidyl tetrahydrophthalate and diglycidyl hexahydrophthalate; aromatic glycidyl esters such as glycidyl benzoate and diglycidyl phthalate), and epoxidized vegetable oils (for example, epoxidized soybean oil, epoxidized linseed oil, and epoxidized cottonseed oil). These epoxy compounds can be used alone or in combination.

[0060] Among these acid scavengers, heterocyclic amines such as pyridine and imidazole, and oxirane compounds such as propylene oxide and butylene oxide are preferred, and C oxirane compounds such as propylene oxide and 1,2-epoxybutane (or 1,2-butylene oxide) are also preferred. 2-6 Alkylene oxides are particularly preferred.

[0061] The proportion of the acid scavenger relative to 1 mole of the raw material is, for example, 1 to 1000 moles, preferably 10 to 800 moles, further preferably 20 to 500 moles, even more preferably 30 to 400 moles, and most preferably 50 to 300 moles. If the proportion of the acid scavenger is too low, the effect of promoting the photocyclization reaction may be reduced, whereas if the proportion is too high, the raw material may not be sufficiently irradiated with light, resulting in a reduced photocyclization reaction.

[0062] (solvent) The photoreaction may be carried out in the presence of a solvent, and is preferably carried out in the presence of a solvent, since the concentrations of the raw materials can be adjusted to concentrations appropriate for the photoreaction.

[0063] Examples of the solvent include aliphatic hydrocarbon solvents (e.g., n-hexane, cyclohexane, methylcyclohexane, etc.), aromatic hydrocarbon solvents (e.g., benzene, toluene, xylene, etc.), ether solvents (e.g., diethyl ether, diisopropyl ether, tetrahydrofuran, 2-methyltetrahydrofuran, 4-methyltetrahydropyran, methyl tert-butyl ether, 1,4-dioxane, cyclopentyl methyl ether, etc.), alcohol solvents (e.g., methanol, ethanol, n-propanol, isopropanol, n-butanol, t-butanol, etc.), and the like. Examples of suitable solvents include alcohol, benzyl alcohol, halogenated solvents (e.g., methylene chloride, chloroform, carbon tetrachloride, chlorobenzene, etc.), ester solvents (e.g., ethyl acetate, propyl acetate, butyl acetate, etc.), ketone solvents (e.g., acetone, methyl ethyl ketone, methyl isobutyl ketone, etc.), nitrile solvents (e.g., acetonitrile, propionitrile, butyronitrile, etc.), amide solvents (e.g., N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, etc.), and sulfoxides (e.g., dimethyl sulfoxide, etc.). These solvents can be used alone or in combination of two or more.

[0064] Among these solvents, hydrocarbon solvents, for example, aliphatic hydrocarbon solvents such as cyclohexane, and aromatic hydrocarbon solvents such as toluene, are preferred for the photocyclization reaction. In particular, when the compound represented by the formula (1) is used as a raw material, X 1 and X 2 In the case of a raw material in which X is a vinylene group or an arylene group, an aromatic hydrocarbon solvent is preferred. 1 and X 2 When is a sulfur atom, an aliphatic hydrocarbon solvent is preferred.

[0065] The ratio of the solvent is adjusted to achieve the desired raw material concentration.

[0066] (object) The target photoreaction product is not particularly limited, but is preferably a cyclic compound (photocyclized product) obtained by a photocyclization reaction, and particularly preferably a fused polycyclic compound, because they are highly stable and can be produced efficiently.

[0067] As the fused polycyclic compound, when the raw material is a compound represented by formula (1), a compound represented by the following formula (2) can be produced.

[0068] [ka]

[0069] (In the formula, ring Z 1 , ring Z 2 , ring Z 3 , R 1 , R 2 , R 3 , m1, m2, m3, X 1 , X 2 and n is the same as above)

[0070] The compound represented by the formula (2) is a compound corresponding to the formula (1), and has a ring Z 1 and Ring Z 2 and Ring Z 3 and a linking group X 1 and X 2A ring structure is formed by bridging carbon atoms adjacent to the carbon atom to which is bonded.

[0071] In particular, as the fused polycyclic compound, the raw material is a compound represented by the formula (1), wherein X 1 is the substituent R 4 In the case of a compound in which n is a vinylene group optionally having the formula (2a) and n is 0, a compound represented by the following formula (2a) can be produced.

[0072] [ka]

[0073] (In the formula, R 4 represents a substituent, m4 represents an integer of 0 or 1 to 2, and ring Z 1 , ring Z 3 , R 1 , R 3 , m1, and m3 are the same as above)

[0074] In the compound represented by the formula (2a), the central benzene ring is the ring Z in the formula (1). 1 and ring Z 3 Among the carbon atoms constituting the linking group X 1 A benzene ring is formed by bridging the carbon atoms adjacent to the carbon atom to which R is bonded. 4 As for R 1 , R 2 and R 3 Examples of the substituents include those exemplified in

[0075] As the fused polycyclic compound, the raw material is a compound represented by the formula (1), wherein X 1 is the substituent R 5 In the case of a compound in which n is a 1,2-phenylene group optionally having the formula (2b) and n is 0, a compound represented by the following formula (2b) can be produced.

[0076] [ka]

[0077] (In the formula, R 5 represents a substituent, m5 represents 0 or an integer of 1 to 4, and ring Z 1 , ring Z 3 , R 1 , R 3 , m1, m3 are the same as above)

[0078] In the compound represented by the formula (2b), the ring Z 1 and ring Z 3 The central benzene ring between 1 and ring Z 3 Among the carbon atoms constituting the linking group X 1 A benzene ring is formed by bridging the carbon atoms adjacent to the carbon atom to which R is bonded. 5 As for R 1 , R 2 and R 3 Examples of the substituents include those exemplified in

[0079] As the fused polycyclic compound, the raw material is a compound represented by the formula (1), wherein X 1 In the case of a compound in which is a sulfur atom and n is 0, a compound represented by the following formula (2c) can be produced.

[0080] [ka]

[0081] (In the formula, ring Z 1 , ring Z 3 , R 1 , R 3 , m1 and m3 are the same as above)

[0082] The compound represented by the formula (4) corresponds to the compound represented by the formula (1), and the central thiophene ring is the ring Z in the formula (1). 1 and ring Z 3 Among the carbon atoms constituting the linking group X 1The thiophene ring is formed by bridging the carbon atoms adjacent to the carbon atom to which the sulfur atom is bonded.

[0083] [Introduction process] The production method of the present invention may include the reaction step and the circulation step, but may further include an introduction step for supplying a reaction liquid containing at least the starting materials to the reaction step.

[0084] In the introducing step, the first reactant liquid containing at least the starting material may be subjected to the reaction step described below.

[0085] The first reactant liquid only needs to contain a raw material (liquid raw material or solid raw material) as a starting material, and may be a liquid raw material alone or a mixed liquid containing the raw material and a solvent. Of these, a mixed liquid containing the raw material and a solvent is preferred because it allows adjustment of the raw material concentration in the first reactant liquid. Furthermore, the mixed liquid containing the raw material and a solvent may be a dispersion containing the raw material and a solvent, or may be a solution containing the raw material and a solvent (a solution in which the raw material is dissolved in the solvent). However, a solution containing the raw material and a solvent is particularly preferred because it allows for easier uniform light irradiation and can improve reaction efficiency.

[0086] The concentration of the starting material in the first reaction solution may be 100 mM or less, for example, 1 to 100 mM, preferably 3 to 50 mM, further preferably 5 to 30 mM, more preferably 7 to 20 mM, and most preferably 8 to 15 mM. If the concentration of the starting material is too high, the reaction efficiency may decrease.

[0087] The method for subjecting the first reactant liquid to the reaction step is not particularly limited, and for example, an inlet (flow inlet) may be provided in a reaction unit for photoreacting the raw materials in the reaction step, and the first reactant liquid may be allowed to flow directly into the reaction unit from the inlet using gravity or the like. However, a method in which an inlet line leading to the reaction unit is provided and the first reactant liquid is allowed to flow into the reaction unit via this inlet line is preferred, as this makes it easier to circulate the first reactant liquid within the manufacturing apparatus.

[0088] The introduction line is not particularly limited in shape or material as long as it can deliver the first reactant liquid to the reaction unit, and may be made of an opaque material. From the viewpoint of easily producing an apparatus for producing a photoreaction product, an introduction line formed of the same tube that is continuous with the reaction flow path of the reaction unit described below is preferred.

[0089] After the introduction line has introduced the first reactant liquid into the reaction unit, the introduction line functions as part of a circulation line for returning the reaction liquid produced in the reaction unit back to the reaction unit.

[0090] In the flow synthesis of the present invention, it is necessary to flow the first reactant liquid within the reaction unit and return the reaction liquid produced in the reaction unit to the reaction unit again, so a liquid delivery means is required to deliver the first reactant liquid and the reaction liquid.

[0091] The position of the liquid delivery means is not particularly limited, and it may be provided in the circulation line described below, but if the production apparatus is equipped with an introduction line, it is preferable to provide the liquid delivery means in the introduction line. The liquid delivery means may be continuously driven so that the circulating liquids in the production apparatus, such as the first reactant liquid and the reaction liquid that has undergone the reaction step described below, flow at a predetermined flow rate.

[0092] The liquid delivery means is not particularly limited as long as it can continuously circulate the reactant liquid and the reaction liquid within the production apparatus and deliver the liquid at a predetermined flow rate. Examples of the liquid delivery means include a liquid delivery pump. Examples of the liquid delivery pump include conventional liquid delivery pumps such as a syringe pump, a plunger pump, a diaphragm pump, and a gear pump.

[0093] When the first reactant liquid is delivered from the introduction line to the reaction unit using a liquid delivery means, it is preferable to provide a storage tank unit and store the first reactant liquid in the storage tank unit. When a storage tank unit is provided, the first reactant liquid can be adjusted in the storage tank unit, and the reaction liquid that has passed through the circulation line may be stored in the storage tank unit. Also, when new raw materials (additional raw materials) are added after the first reactant liquid is introduced, the additional raw materials may be supplied to the storage tank unit. The storage tank unit may be provided with a stirring means for stirring the first reactant liquid and the reaction liquid.

[0094] [Reaction process] In the reaction step, a reactant liquid containing at least the raw materials is irradiated with light while flowing to cause a photoreaction, thereby obtaining a reaction liquid containing a photoreaction product and unreacted raw materials.

[0095] In the reaction step, the reactant liquid is either the first reactant liquid prepared in the introduction step, or a reaction liquid (second reactant liquid) obtained by subjecting the first reactant liquid to the reaction step one or more times. That is, in the present invention, the reaction liquid obtained in the reaction step is repeatedly subjected to the reaction step in the circulation step described below, so that in the first reaction step, the starting material corresponds to the reaction target, and in the second and subsequent reaction steps, the unreacted material that was not photoreacted in the reaction step corresponds to the reaction target, and when a new material is added, the additional material also corresponds to the reaction target.

[0096] Such a reaction process is carried out in a reaction unit, in which a reactant liquid is irradiated with light while flowing to cause a photoreaction of the raw materials, thereby obtaining a reaction liquid containing the target substance and unreacted raw materials. The reaction unit has at least a light source unit and a reaction flow path arranged so that light from the light source unit can be irradiated, and the raw material-containing liquid passing through the reaction flow path is irradiated with light, causing the raw materials to photoreact and producing a photoreaction product.

[0097] (Light source part) The light source unit has at least one light source. There are no particular limitations on the light source unit as long as it can irradiate the raw material-containing liquid passing through the reaction channel with light.

[0098] The light source unit may be configured as an integrated unit, with the light source disposed inside a light-transmitting container, and the light source and an outer case (casing) for housing the light source. The outer case of the light source may be formed from a transparent material that can transmit light from the light source, for example, a transparent resin such as an acrylic resin or a fluororesin; glass such as quartz glass or lime soda glass; quartz; or a transparent inorganic material such as magnesium fluoride or calcium fluoride. Furthermore, the reaction unit may be equipped with a temperature regulator, and the outer case may be a water-cooled jacket (casing or cooling pipe) arranged to cover the light source. When the light source unit is equipped with a water-cooled jacket (water jacket) as the outer case, the reaction temperature may be adjusted by supplying cooling water to the water-cooled jacket.

[0099] Examples of light sources include xenon lamps, electrodeless lamps, low-pressure mercury lamps, medium-pressure mercury lamps, high-pressure mercury lamps, ultra-high-pressure mercury lamps, acetylene lamps, light-emitting diodes, and fluorescent lamps. A combination of multiple light sources may be used, or multiple light sources with different wavelengths, intensities, etc. may be combined. The light source can be appropriately selected depending on the type of photoreaction product. In the photocyclization reaction, high-pressure mercury lamps, ultra-high-pressure mercury lamps, and light-emitting diodes are preferred due to their high reactivity, and high-pressure mercury lamps are particularly preferred.

[0100] (Reaction channel) The reaction flow path is not particularly limited as long as it is disposed in a position within the reaction unit where light from the light source can be irradiated and is a continuous, light-transmitting flow path through which the raw material-containing liquid can flow.

[0101] The shape of the reaction flow path is not particularly limited as long as it is a shape that allows the raw material-containing liquid to pass around the light source unit and thereby irradiate the raw material with light. The shape of the reaction flow path may be a cylindrical flow path (ring-shaped in cross section) that covers the light source unit, but a flow path that extends linearly (or fibrously) along the surface of the light source unit (linear flow path) is preferred because it makes it easier to uniformly irradiate the raw material with light while the raw material-containing liquid flows. The linear flow path is not particularly limited as long as it is linear, but can usually be formed using a reaction line such as a tube or hose.

[0102] The cross-sectional shape of the linear flow channel is not particularly limited, and examples thereof include a circle, an approximately circle, an ellipse, a polygon (e.g., a triangle, a rectangle, a hexagon, etc.), etc. Among these cross-sectional shapes, a circle, an approximately circle, and an ellipse are preferred, and a circle is particularly preferred, because the reaction line can be easily bent in a wide range of directions and can be easily disposed in the light source unit.

[0103] The cross-sectional area of ​​the linear flow path is 100 mm 2 It may be less than 0.5 to 100 mm, for example. 2 , preferably 1 to 50 mm 2 , and more preferably 1.5 to 30 mm 2 , more preferably 2 to 10 mm 2 , most preferably 2.5 to 5 mm 2 If the cross-sectional area of ​​the linear flow channel is too large, the reaction efficiency may decrease.

[0104] The length (channel length) of the reaction channel (particularly, a linear channel) may be, for example, 0.1 m or more (particularly, 1 m or more), for example, 0.1 to 100 m, preferably 1 to 50 m, further preferably 3 to 30 m, more preferably 5 to 20 m, and most preferably 7 to 10 m. If the length of the reaction channel is too short, the time for continuous light irradiation will be shortened, which may result in a decrease in reaction efficiency, whereas if it is too long, the production equipment may become large.

[0105] The position of the linear flow path is not particularly limited as long as it is located at a position within the flow path where light can be irradiated. The linear flow path may be located away from the light source unit, but from the viewpoint of ease of installation, it is preferably located along the surface of the light source unit, more preferably the reaction line is wound around the surface of the light source unit, and even more preferably the reaction line is wound spirally around the surface of the light source unit. In the method of winding the reaction line around the surface of the light source unit, the reaction line can be easily formed without gaps on the surface of the light source unit, and the area where the linear flow path can be irradiated with light can be easily enlarged.

[0106] Components for forming reaction flow paths such as reaction lines are made of transparent materials to allow light from a light source to reach the raw materials. Examples of transparent materials include transparent resins such as polyolefin resins, (meth)acrylic resins, polyester resins, polycarbonate resins, polyamide resins, fluororesins, and cellulose derivatives; and transparent inorganic materials such as glass. Among these, transparent resins are preferred because of their high flexibility and ease of manufacturing the production equipment, and fluororesins such as tetrafluoroethylene-hexafluoropropylene copolymer (FEP) are particularly preferred because of their excellent chemical resistance.

[0107] (Reaction conditions) The wavelength of light irradiated in the photoreaction can be selected depending on the type of photoreaction product, and in the photocyclization reaction, it can be selected from the range of about 10 to 800 nm, for example, 100 to 700 nm, preferably 200 to 500 nm, further preferably 250 to 400 nm, more preferably 300 to 380 nm, and most preferably 350 to 370 nm. The light irradiated in the photocyclization reaction may be ultraviolet light.

[0108] The amount of light (especially ultraviolet light) to be irradiated (exposure amount) is not particularly limited, and in the case of a high-pressure mercury lamp, irradiation may be performed using a high-pressure mercury lamp of, for example, 100 W or more, preferably 100 to 1000 W, further preferably 200 to 800 W, and even more preferably 300 to 500 W. If the exposure amount is too small, the reaction efficiency may decrease.

[0109] The reaction temperature for the photoreaction can be selected depending on the type of photoreaction product, and in the case of a photocyclization reaction, it is, for example, -10°C to 100°C, preferably 0 to 80°C, further preferably 5 to 70°C, even more preferably 10 to 60°C, and most preferably 15 to 40°C. If the reaction temperature is too low, the reaction efficiency may decrease, and if it is too high, by-products may be generated, resulting in a decrease in yield. The reaction temperature may be adjusted using a temperature regulator such as the water-cooled jacket.

[0110] In the photocyclization reaction, the flow rate of the reactant solution passing through the reaction channel is, in terms of linear velocity, 10 mm / sec or more (particularly 50 mm / sec or more), for example, 10 to 1000 mm / sec, preferably 30 to 500 mm / sec, more preferably 50 to 300 mm / sec, more preferably 80 to 200 mm / sec, and most preferably 100 to 150 mm / sec, and is, in terms of volumetric flow rate, 1 mL / min or more (particularly 15 mL / min or more), for example, 1 to 100 mL / min, preferably 3 to 80 mL / min, more preferably 5 to 50 mL / min, more preferably 10 to 40 mL / min, and most preferably 15 to 30 mL / min. If the flow rate of the reactant solution is too low, the reaction efficiency may decrease and the reaction time may become longer. As will be shown in the Reference Example in the Examples to be described later, in conventional flow synthesis, it has been common technical knowledge that in order to improve reaction efficiency, a slow flow rate is advantageous in order to sufficiently irradiate the raw materials with light. However, in the production method of the present invention, unexpectedly, by increasing the flow rate, it is possible to shorten the reaction time and improve the reaction efficiency while maintaining a high yield.

[0111] The flow rate of the reactant liquid in the introduction step described above and the flow rate of the reaction liquid in the circulation step described below are not particularly limited, but when a liquid delivery pump is used as the liquid delivery means, the flow rate is usually the same as the flow rate in the reaction step.

[0112] In the photocyclization reaction, the concentration of the raw materials in the reaction solution in the reaction step may be 100 mM or less (particularly 15 mM or less), for example, 1 to 100 mM, preferably 2 to 30 mM, further preferably 3 to 20 mM, more preferably 5 to 15 mM, and most preferably 7 to 13 mM. If the concentration is too high, the reaction time may be prolonged, and the reaction efficiency may decrease. In the present invention, by flowing the reaction solution having such raw material concentrations at the above-mentioned flow rate, the desired photoreaction product (particularly, a photocyclized product) can be obtained in a short time and with high yield. Furthermore, by maintaining the raw material concentrations in the reaction solution at such low concentrations and adding new raw materials in the raw material addition step described below, the desired photoreaction product (particularly, a photocyclized product) can be obtained with higher reaction efficiency.

[0113] [Circulation process] In the circulation process, the reaction solution obtained in the reaction process is returned to the reaction process as a new reactant solution, thereby photoreacting unreacted raw materials that did not completely react in the reaction process, thereby improving the yield of the desired photoreaction product. In conventional flow synthesis, reaction efficiency was improved by increasing the volume or length of the reaction channel or slowing the flow rate to extend the residence time of the reactant solution in the reaction process. In contrast, in the present invention, reaction efficiency can be improved by repeatedly subjecting the reaction solution containing unreacted raw materials and the desired photoreaction product to photoreaction as the reactant solution without increasing the volume or length of the reaction channel or slowing the flow rate. In particular, as described above, in conventional flow synthesis, the flow rate of the reactant was slowed to extend the residence time of the reactant solution. However, in the present invention, production efficiency can be improved by unexpectedly increasing the flow rate of the reactant solution.

[0114] The method for returning the reaction liquid to the reaction process as a new reactant liquid is not particularly limited. For example, a preferred method is to provide a circulation line for returning the reaction liquid containing the target photoreaction product and unreacted raw materials produced in the reaction process to the reaction unit or the introduction line, and to allow the reaction liquid to flow into the reaction unit via this circulation line. When combined with the introduction line, it is preferable to provide a storage tank unit for storing the first reactant liquid containing the starting material and the reaction liquid. When a storage tank unit is provided, both the circulation line and the introduction line are connected to the storage tank unit, and the reaction liquid transported to the storage tank unit via the circulation line is supplied again to the reaction unit as the reaction target via the introduction line. Therefore, after the introduction of the first reactant liquid, the introduction line for introducing the first reactant liquid containing the starting material functions as a circulation line for returning the reaction liquid to the reaction unit via the circulation line.

[0115] In addition, when a storage tank unit is provided, the reaction liquid that has passed through the circulation line may be temporarily stored in the storage tank unit and then supplied to the reaction unit via the introduction line as a new reactant liquid.

[0116] The circulation line is not particularly limited in shape or material as long as it can send the reaction liquid as a new reactant liquid to the reaction unit, storage tank unit, etc., and may be made of an opaque material. From the viewpoint of easily manufacturing an apparatus for producing a photoreaction product, a circulation line formed from the same tube that is continuous with the reaction flow path of the reaction unit is preferred.

[0117] In the production method of the present invention, the cycle (number of cycles) from the reaction step to the circulation step may be one or more and is not particularly limited, but from the viewpoint of improving the reaction efficiency, it is preferably three or more, more preferably five or more, and even more preferably eight or more. In particular, when the photoreaction is a photocyclization reaction, the photocyclized product produced is stable, so that the photocyclized product can be produced in high yield even with a large number of cycles.

[0118] [Analysis process] In the production method of the present invention, although not necessarily required, the progress of the reaction of the photoreaction product in the reaction step may be monitored using an analytical device. A conventional analytical device such as a gas chromatograph can be used as the analytical device. The location and method of installation of the analytical device are not particularly limited, and the reaction solution may be sampled and analyzed from the circulation line, introduction line, storage tank unit, etc., or the analytical device may be installed in the circulation line, introduction line, or storage tank unit for analysis. Of these, installing the analytical device in the circulation line or storage tank unit is preferred, and installing the analytical device in the circulation line is particularly preferred.

[0119] In the analysis step, the progress of the reaction of the photoreaction product can be evaluated, for example, by evaluating the ratio of the target photoreaction product to the raw materials (the ratio of the target photoreaction product to the total amount of the target photoreaction product and the raw materials). This can be used as a basis for determining the end of the reaction, the timing for adding new raw materials (described below), and the timing for purifying the reaction solution (described below). For example, when the ratio calculated from the concentration measured by gas chromatography reaches 98% or more, the reaction can be terminated and the reaction solution recovered. Alternatively, at this point, new raw materials can be added directly to the reaction solution and the reaction can be continued. Furthermore, after purifying the reaction solution at this point, new raw materials can be added and the reaction can be continued.

[0120] In this specification and claims, the ratio calculated from the concentrations measured using gas chromatography (the ratio of the target photoreaction product to the total amount of the target photoreaction product and raw material) is referred to as the raw material conversion rate.

[0121] In this specification and claims, the reaction is considered to be complete when the raw material conversion rate reaches 98% or more.

[0122] [Raw material addition process] In the production method of the present invention, a first reactant liquid containing a starting material is subjected to the reaction step in the introduction step, and the production method may further include a raw material addition step of adding a new raw material (additional raw material) to the introduction line or reaction unit after the first reactant liquid is introduced into the introduction line or reaction unit and the liquid transfer is started. In the production method of the present invention, by providing the raw material addition step, the reaction efficiency of the photoreaction product can be improved.

[0123] The additional raw material may be added in an amount to replenish the raw material consumed in the reaction. Specifically, the additional raw material may be added in an amount such that the raw material concentration in the reactant liquid (first reactant liquid or second reactant liquid) as the reaction target is 100 mM or less, for example, 1 to 100 mM, preferably 3 to 50 mM, further preferably 5 to 30 mM, more preferably 7 to 20 mM, and most preferably 8 to 15 mM. If the raw material concentration exceeds the above range by adding new raw material, the reaction efficiency may decrease.

[0124] The method for adding the additional raw material is not particularly limited as long as the raw material concentration in the reactant solution is adjusted to be within the above range. For example, as described above, the additional raw material may be added to the reaction solution after the reaction has finished and the raw material conversion rate has reached 98% or more, or the additional raw material may be added to the reaction solution in which unreacted raw material remains and the reaction has not finished.

[0125] The additional raw materials may be added, for example, simultaneously with the introduction of the first reactant liquid containing the starting materials or after a predetermined time has elapsed since the introduction, in an amount that replenishes the raw materials consumed in the reaction step. However, from the viewpoint of simple control of the raw material concentration in the reactant liquid, a method of intermittently adding the raw materials after the introduction of the first reactant liquid is preferred, and a method of intermittently adding the raw materials at regular intervals after the introduction of the first reactant liquid is also preferred. For example, after the introduction of the first reactant liquid, the additional raw materials may be added, for example, at intervals of 10 to 60 minutes (preferably at intervals of 20 to 40 minutes, and more preferably at intervals of 25 to 35 minutes). The number of times the additional raw materials are added (excluding the number of times the starting materials are introduced) is, for example, 1 to 12 times, preferably 2 to 10 times, more preferably 3 to 8 times, and more preferably 4 to 6 times.

[0126] The method for introducing the additional raw material is not particularly limited, and the additional raw material may be introduced from an introduction line, a circulation line, or a storage tank unit. However, when the production apparatus has a storage tank unit, it is preferable, from the standpoint of simplicity, to introduce the additional raw material into the storage tank unit and supply (transport) it to the reaction unit via the introduction line by a liquid transport means.

[0127] [Refining process] The production method of the present invention may further include a purification step of purifying the reaction solution obtained in the reaction step.

[0128] In the purification step, the reaction solution obtained in the reaction step may be purified using a porous adsorbent. The porous adsorbent is preferably an inorganic porous adsorbent, such as activated carbon, zeolite, molecular sieves, amorphous silica, silica gel, bentonite, activated alumina, or activated clay. These porous adsorbents can be used alone or in combination.

[0129] Among these porous adsorbents, silica gel is preferred because of its high purification efficiency.

[0130] The average pore size of the porous adsorbent (particularly silica gel) is, for example, 1 to 100 nm, preferably 2 to 50 nm, further preferably 3 to 30 nm, even more preferably 5 to 20 nm, and most preferably 6 to 10 nm. If the pore size is too small, it may be difficult to perform treatment in a short time, and if it is too large, the purification efficiency may decrease.

[0131] In this specification and claims, the average pore size of the porous adsorbent can be measured by a nitrogen-containing adsorption method using nitrogen gas.

[0132] The BET specific surface area of ​​porous adsorbents (especially silica gel) is, for example, 10 to 1000 m 2 / g, preferably 100 to 800m 2 / g, more preferably 200 to 600m 2 / g, more preferably 300 to 550m 2 / g, most preferably 400-500m 2 If the BET specific surface area is too small, the purification efficiency may decrease, whereas if it is too large, it may become difficult to treat in a short time.

[0133] In this specification and claims, the BET specific surface area of ​​the porous adsorbent can be measured by the BET method using nitrogen gas.

[0134] Examples of the shape of the porous adsorbent (particularly silica gel) include spherical (true spherical or approximately spherical), ellipsoidal, polygonal (polygonal pyramidal, cubic, rectangular parallelepiped, etc.), plate-like, rod-like, fibrous, and irregular shapes. These shapes may be the same shape or a combination of different shapes. Of these, spherical is preferred.

[0135] The average particle size of the porous adsorbent (particularly silica gel) is, for example, 1 to 500 μm, preferably 10 to 300 μm, further preferably 30 to 200 μm, even more preferably 50 to 150 μm, and most preferably 80 to 120 μm. If the average particle size is too small, it may be difficult to process in a short time, and if it is too large, the purification efficiency may decrease.

[0136] In this specification and claims, the average particle size of the porous adsorbent can be measured on a volume basis based on the particle size distribution measured using a laser diffraction scattering particle size distribution measuring device.

[0137] In the purification step, in addition to the treatment using such a porous adsorbent, conventional purification means may be used in combination, such as transfer, salting out, distillation, solvent removal, precipitation, crystallization, recrystallization, decantation, extraction, drying, washing, chromatography, etc.

[0138] The reaction liquid obtained in the purification step may be returned to the reaction step as a new reactant liquid. By providing a purification step in the circulation step, it is possible to remove photoreaction products as by-products in addition to the raw materials and catalyst, thereby improving the reaction efficiency of the photoreaction products. When the purified reaction liquid is subjected to the reaction step, the reaction liquid to be purified may be a reaction liquid in which the reaction has terminated with a raw material conversion rate of 98% or more, or it may be a reaction liquid in which unreacted raw materials remain. Furthermore, the reaction liquid obtained in the purification step may contain unreacted raw materials and / or catalyst remaining.

[0139] When a reaction solution containing unreacted raw materials is subjected to a purification step, the raw material conversion rate in the reaction solution may be 50% or more, preferably 60 to 97%, further preferably 70 to 95%, further preferably 80 to 94%, and most preferably 90 to 93%. If the raw material conversion rate is too low, there is a risk of a decrease in reaction efficiency.

[0140] Among these, it is preferable to subject the reaction liquid in which the reaction has been completed with a raw material conversion rate of 98% or more to the purification step, in order to improve the reaction efficiency.

[0141] The reaction solution purified in the purification step may be recovered as the desired photoreaction product as it is, or may be returned to the reaction step as a new reactant solution.

[0142] When returning the purified reaction solution to the reaction step, it may be returned to the reaction step after adding new raw materials, or it may be returned to the reaction step without adding new raw materials. Of these methods, it is preferable to provide a raw material addition step, add new raw materials to the purified reaction solution, and continue the reaction, in order to improve the reaction efficiency.

[0143] When the purified reaction liquid is returned to the reaction step as a new reactant liquid, the purified reaction liquid may be taken out from the circulation line or the storage tank unit and subjected to the purification step intermittently, and then returned to the reaction step, or the purification step may be incorporated into the circulation line to continuously purify the reaction liquid and then returned to the reaction step as is.

[0144] [Photoreaction product manufacturing equipment] The manufacturing apparatus for manufacturing a photoreaction product of the present invention includes a liquid delivery means for introducing a reactant liquid containing at least raw materials into a reaction unit and causing it to flow within the reaction unit, a reaction unit for irradiating the reactant liquid with light while the reactant liquid is flowing to cause a photoreaction of the raw materials, thereby obtaining a reaction liquid containing a photoreaction product and unreacted raw materials, and a circulation line for returning the reaction liquid to the reaction unit and subjecting it to the reaction process again.

[0145] FIG. 1 shows a schematic diagram of an example of an apparatus for producing a photoreaction product according to the present invention.

[0146] In the example of FIG. 1, the manufacturing apparatus 1 includes: a storage tank unit 2 for storing a reactant liquid containing raw materials; an introduction line 3 for introducing the reactant liquid 2a stored in the storage tank unit 2 into the reaction unit 5 from an introduction port 3a; a liquid sending means 4 for sending the reactant liquid 2a to the reaction unit 5 through the introduction line 3 and circulating the reactant liquid 2a within the production apparatus 1; a reaction unit 5 for irradiating the reactant solution 2a introduced through the introduction line 3 with light to cause a photoreaction, thereby obtaining a reaction solution containing a target photoreaction product and unreacted raw materials; a circulation line 6 for returning the reaction liquid to the storage tank unit 2 and introducing it again into the reaction unit 5 via an introduction line 3; The circulation line 6 is provided with an analysis means 7 for evaluating the reaction status of the target photoreaction product.

[0147] The reaction unit 5 is formed of a light source section 5b for irradiating light to the raw materials contained in the reaction liquid 2a to cause a photoreaction, and a reaction line 5a that is wrapped around the outer periphery of the light source section 5b and has a reaction flow path inside. Furthermore, the light source section 5b has a cylindrical light source 5b1, and a water-cooled jacket 5b2 disposed on the outer periphery of the light source 5b1. The reaction temperature in the reaction unit 5 can be adjusted by sending cooling water into the water-cooled jacket 5b2 using a cooling means 5b3.

[0148] The production apparatus of the present invention is not limited to the production apparatus shown in Fig. 1 as long as it includes at least the liquid phase means, the reaction unit, and the circulation line. For example, the production apparatus of the present invention may further include a purification means for purifying the reaction liquid produced in the reaction unit 5. The purification means may be disposed in the circulation line 6, similar to the analysis means 7, or may be disposed separately from the circulation line 6 in order to purify the reaction liquid (reacted liquid 2a) taken out from the circulation line 6 or the storage tank unit 2. [Example]

[0149] The present invention will be described in more detail below based on examples, but the present invention is not limited to these examples. Details of the apparatus used and the evaluation method are shown below.

[0150] [Device] High-pressure mercury lamp: "HL400BH-8" manufactured by Sen Special Light Source Co., Ltd. FEP tube: AS ONE Corporation, inner diameter 2 mm x outer diameter 3 mm x length 820 cm Liquid transfer pump: KNF Corporation "Corrosion-resistant diaphragm metering pump (SIMDOS02) FEM1.02FT.18S" Silica gel: "CHROMATOREX PSQ100B" manufactured by Fuji Silysia Chemical Ltd.

[0151] [GC] The reaction liquid was analyzed using a gas chromatography GC device (Shimadzu Corporation "GC-2010 Plus," column: Agilent J&W DB-5, detector: flame ionization detector (FID)). The column temperature was maintained at 200-290°C for 2 minutes at the start of the measurement, then increased at a rate of 5-10°C per minute until the column temperature reached 250-325°C. The concentrations of the raw materials and target substance in the reaction liquid sampled during or after the flow were measured, and the raw material conversion rate (the ratio of the target substance to the total amount of the raw materials and target substance) was calculated.

[0152] The details of the measurement conditions are as follows.

[0153] In the synthesis of benzodithiophene, the column temperature was maintained at 200°C for 2 minutes at the start of the measurement, and then the temperature was increased at a rate of 5°C per minute until the column temperature reached 250°C.

[0154] In the synthesis of dinaphthothiophene, the column temperature was kept at 290°C for 2 minutes at the start of the measurement, and then the temperature was increased at a rate of 10°C per minute until the column temperature reached 325°C.

[0155] For the synthesis of phenanthrene, 3,6-dimethylphenanthrene, and 8-bromonaphtho[2,1-b]thiophene, the column temperature was kept at 200°C for 2 minutes at the start of the measurement, and then the temperature was increased at 8°C per minute until the column temperature reached 260°C.

[0156] In the synthesis of 3,6-dibromophenanthrene, the column temperature was kept at 240°C for 2 minutes at the start of the measurement, and then the temperature was increased at a rate of 8°C per minute until the column temperature reached 280°C.

[0157] [ 1 H-NMR] To identify the target substance, the sample was dissolved in a heavy solvent (CDCl3) containing tetramethylsilane as an internal standard substance, and a nuclear magnetic resonance spectrometer (JEOL Ltd., "JNM-ECZL400R") was used. 1 H-NMR spectrum was measured.

[0158] [Reference examples 1~4] (Batch Flow Synthesis of Benzodithiophenes)

[0159] [ka]

[0160] A sample solution was prepared by adding 193 mg (1 mmol) of 1,2-bis(thiophen-2-yl)ethene and 7.65 mg (0.03 mmol) of iodine to a 100 mL two-necked spout and dissolving them in 100 mL of toluene.

[0161] An FEP tube was tightly wound spirally around the cooling tube of a high-pressure mercury lamp, and the FEP tube was washed with toluene, after which the toluene was drained. The FEP tube wrapped around the high-pressure mercury lamp was connected to a two-necked spout filled with the sample solution, and flow synthesis was performed while irradiating the sample solution with ultraviolet light (>300 nm) using a liquid delivery pump and varying the flow rate as shown in Table 1. The raw material conversion rate was measured, and the results are shown in Table 1.

[0162] [Table 1]

[0163] As is clear from Table 1, in conventional batch flow synthesis, the raw material conversion rate increased as the flow rate decreased, and the reaction was completed by reducing the volumetric flow rate to 0.5 mL / min.

[0164] [Example 1] (Circulating flow synthesis of benzodithiophene: flow rate 10 mL / min, raw material concentration 10 mM / iodine 0.1 eq) A sample solution was prepared by adding 193 mg (1 mmol) of 1,2-bis(thiophen-2-yl)ethene and 25.5 mg (0.1 mmol) of iodine to a 100 mL three-necked flask and dissolving them in 100 mL of toluene.

[0165] The FEP tube was tightly spirally wrapped around the cooling tube of the high-pressure mercury lamp, washed with toluene, and then the toluene was drained. The FEP tube wrapped around the high-pressure mercury lamp was connected to a three-neck flask filled with the sample solution, and the flow-type production apparatus shown in Figure 1 was assembled using a liquid pump. The sample solution was circulated while irradiating it with ultraviolet light (>300 nm) at a flow rate of 10 mL / min (53 mm / sec). The reaction was monitored by GC and terminated 90 minutes later, when the raw material conversion rate reached 99.6%. The raw material conversion rate was measured over time and the results are shown in Table 2.

[0166] [Table 2]

[0167] Since the flow rate was 10 mL / min for 100 mL of solution, one cycle took 10 minutes. As can be seen from Table 2, the raw material conversion rate was 98% after 60 minutes, which means that the reaction was nearly complete around the 6th cycle.

[0168] After 90 minutes of reaction, the reaction mixture was washed with sodium thiosulfate and water and then salted out. Sodium sulfate was then added to the mixture, which was then dried and concentrated. The concentrate was purified using a silica gel column (approximately 20 cm, hereinafter, unless otherwise specified, this silica gel column was used) using hexane as the developing solvent, and then dried under reduced pressure to obtain 166 mg of solid benzodithiophene (yield 87%).

[0169] [Example 2] (Circulating flow synthesis of benzodithiophene: flow rate 20 mL / min, raw material concentration 10 mM / iodine 0.1 eq) A 100 mL three-necked flask was charged with 193 mg (1 mmol) of 1,2-bis(thiophen-2-yl)ethene and 26.2 mg (0.1 mmol) of iodine, and the mixture was dissolved in 100 mL of toluene to prepare a sample solution.

[0170] A flow-type production apparatus was assembled in the same manner as in Example 1. The sample solution was circulated at a flow rate of 20 mL / min (106 mm / sec) while being irradiated with ultraviolet light (>300 nm). The reaction was monitored by GC and terminated 45 minutes later when the raw material conversion rate reached 99.5%. The results of measuring the raw material conversion rate over time are shown in Table 3.

[0171] [Table 3]

[0172] For a 100 mL solution, the flow rate was 20 mL / min, so one cycle took 5 minutes. As can be seen from Table 3, the raw material conversion rate was 99% after 30 minutes, which means that the reaction was nearly complete around the 6th cycle.

[0173] After 45 minutes of reaction, the reaction mixture was washed with sodium thiosulfate and water, followed by salting out. Sodium sulfate was then added to the mixture, which was then dried and concentrated. The concentrate was purified using a silica gel column with hexane as the developing solvent, and then dried under reduced pressure to obtain 165 mg of solid benzodithiophene (yield 86%).

[0174] As is clear from the results in Table 3, in Example 2, by delivering the sample solution at a flow rate twice as fast as in Example 1, not only did the reaction proceed in a shorter time, but the yield was also comparable. Such results were unexpected for those skilled in the art, considering the results of the Reference Examples and the conventional common technical knowledge that suggested that a reduced flow rate was necessary to improve reaction efficiency in flow synthesis.

[0175] [Example 3] (Circulating flow synthesis of benzodithiophene: flow rate 20 mL / min, raw material concentration 20 mM / iodine 0.1 eq) A 100 mL three-necked flask was charged with 384 mg (2 mmol) of 1,2-bis(thiophen-2-yl)ethene and 51.0 mg (0.2 mmol) of iodine, and the mixture was dissolved in 100 mL of toluene to prepare a sample solution.

[0176] A flow-type production apparatus was assembled in the same manner as in Example 1. The sample solution was circulated at a flow rate of 20 mL / min while irradiating it with ultraviolet light (>300 nm). The reaction was monitored by GC and terminated 60 minutes later when the raw material conversion rate reached 99.4%. In this example, this means that the reaction was nearly completed after 12 cycles. The results of measuring the raw material conversion rate over time are shown in Table 4.

[0177] [Table 4]

[0178] The reaction mixture was washed with sodium thiosulfate and water, followed by salting out. Sodium sulfate was then added to the mixture, which was then dried and concentrated. The concentrate was purified using a silica gel column with hexane as the developing solvent, and then dried under reduced pressure to obtain 316 mg (83% yield) of solid benzodithiophene.

[0179] [Example 4] (Circulating flow synthesis of benzodithiophene: flow rate 20 mL / min, raw material concentration 10 mM x 2 / iodine 0.1 eq) A 100 mL three-necked flask was charged with 193 mg (1 mmol) of 1,2-bis(thiophen-2-yl)ethene and 25.0 mg (0.1 mmol) of iodine, and the mixture was dissolved in 100 mL of toluene to prepare a sample solution.

[0180] A flow-type production apparatus was assembled in the same manner as in Example 1. The sample solution was circulated at a flow rate of 20 mL / min while irradiating it with ultraviolet light (>300 nm). The reaction was monitored by GC, and it was confirmed that the raw material conversion rate reached 99.9% after 45 minutes. The results of measuring the raw material conversion rate over time are shown in Table 5.

[0181] [Table 5]

[0182] As is clear from Table 5, the raw material conversion rate was 99% after 30 minutes, which means that the reaction was nearly completed around the 6th cycle.

[0183] After 45 minutes, the disappearance of the raw material was confirmed. 193 mg (1 mmol) of 1,2-bis(thiophen-2-yl)ethene was then added, and the sample solution was circulated again at a flow rate of 20 mL / min while irradiating the sample solution with UV light (>300 nm). The reaction was monitored by GC, and the reaction was terminated after 45 minutes when the raw material conversion rate reached 99.8%. The results of measuring the raw material conversion rate after adding the raw material are shown in Table 6.

[0184] [Table 6]

[0185] As is clear from Table 6, even after the addition of raw materials, the raw material conversion rate was 99.2% after 30 minutes, which means that the reaction was nearly completed around cycle 6. Since the reaction was also completed in 6 cycles before the addition of raw materials, the reaction was essentially nearly completed in a total of 12 cycles.

[0186] In Table 6, the initial raw material conversion rate is 44% because benzodithiophene exists before the raw material is added.

[0187] After 45 minutes of reaction from the addition of the raw materials, the reaction solution was washed with sodium thiosulfate and water and then salted out. Next, sodium sulfate was added, dried, and concentrated. The concentrate was purified using a silica gel column using hexane as the developing solvent and then dried under reduced pressure to obtain 337 mg (88% yield) of solid benzodithiophene.

[0188] Compared to Example 3, in which the raw material concentration was 20 mM, the yield was slightly improved in Example 4, even though the total amount of raw material was the same and the reaction time was approximately the same. Therefore, comparing Example 3 and Example 4, higher reaction efficiency was observed when the raw material concentration was 10 mM and reacted in two separate reactions than when the raw material concentration was 20 mM.

[0189] [Example 5] (Circulation flow synthesis of benzodithiophene: flow rate 20 mL / min, raw material concentration 30 mM / iodine 0.1 eq) A 100 mL three-necked flask was charged with 577 mg (3 mmol) of 1,2-bis(thiophen-2-yl)ethene and 75.6 mg (0.3 mmol) of iodine, and the mixture was dissolved in 100 mL of toluene to prepare a sample solution.

[0190] A flow-type production apparatus was assembled in the same manner as in Example 1. The sample solution was circulated while irradiating it with ultraviolet light (>300 nm) at a flow rate of 20 mL / min. The reaction was monitored by GC and terminated 90 minutes later when the raw material conversion rate reached 99%. In this example, this means that the reaction was nearly complete around the 18th cycle. The results of measuring the raw material conversion rate over time are shown in Table 7.

[0191] [Table 7]

[0192] The resulting reaction solution was washed with sodium thiosulfate and water, followed by salting out. Next, sodium sulfate was added to the mixture, which was then dried and concentrated. The concentrate was purified using a silica gel column using hexane as the developing solvent, and then dried under reduced pressure to obtain 478 mg of solid benzodithiophene (yield 83%).

[0193] [Example 6] (Circulation flow synthesis of benzodithiophene: flow rate 20 mL / min, raw material concentration 10 mM x 3 / iodine 0.1 eq) A 100 mL three-necked flask was charged with 193 mg (1 mmol) of 1,2-bis(thiophen-2-yl)ethene and 25.0 mg (0.1 mmol) of iodine, and the mixture was dissolved in 100 mL of toluene to prepare a sample solution.

[0194] A flow-type production apparatus was assembled in the same manner as in Example 1. The sample solution was circulated while irradiating it with ultraviolet light (>300 nm) at a flow rate of 20 mL / min. The reaction was monitored by GC. After confirming that the raw material had disappeared after 30 minutes, when the raw material conversion rate reached 99%, 193 mg (1 mmol) of 1,2-bis(thiophen-2-yl)ethene was added, and the sample solution was again circulated while irradiating it with ultraviolet light (>300 nm) at a flow rate of 20 mL / min. After confirming that the raw material had disappeared after 30 minutes, additional raw material was added in the same manner, and the solution was irradiated with light again and circulated (a total of two additional raw material additions).

[0195] The resulting reaction solution was washed with sodium thiosulfate and water, followed by salting out. Next, sodium sulfate was added to the mixture, which was then dried and concentrated. The concentrate was purified using a silica gel column using hexane as the developing solvent, and then dried under reduced pressure to obtain 504 mg (yield 88%) of solid benzodithiophene.

[0196] [Example 7] (Circulation flow synthesis of benzodithiophene: flow rate 20 mL / min, raw material concentration 10 mM x 4 / iodine 0.1 eq) A 100 mL three-necked flask was charged with 193 mg (1 mmol) of 1,2-bis(thiophen-2-yl)ethene and 25.0 mg (0.1 mmol) of iodine, and the mixture was dissolved in 100 mL of toluene to prepare a sample solution.

[0197] A flow-type production apparatus was assembled in the same manner as in Example 1. The sample solution was circulated while irradiating it with ultraviolet light (>300 nm) at a flow rate of 20 mL / min. The reaction was monitored by GC. After confirming that the raw material had disappeared after 30 minutes, when the raw material conversion rate reached 99%, 193 mg (1 mmol) of 1,2-bis(thiophen-2-yl)ethene was added, and the sample solution was again circulated while irradiating it with ultraviolet light (>300 nm) at a flow rate of 20 mL / min. After confirming that the raw material had disappeared after 30 minutes, the process of adding additional raw material, irradiating it with light, and circulating it was repeated two more times (a total of three additions of additional raw material).

[0198] The resulting reaction solution was washed with sodium thiosulfate and water, followed by salting out. Next, sodium sulfate was added to the mixture, which was then dried and concentrated. The concentrate was purified using a silica gel column using hexane as the developing solvent, and then dried under reduced pressure to obtain 657 mg (86% yield) of solid benzodithiophene.

[0199] [Example 8] (Circulating flow synthesis of benzodithiophene: flow rate 20 mL / min, raw material concentration 60 mM / iodine 0.1 eq) A 100 mL three-necked flask was charged with 1.15 g (6 mmol) of 1,2-bis(thiophen-2-yl)ethene and 152 mg (0.6 mmol) of iodine, and the mixture was dissolved in 100 mL of toluene to prepare a sample solution.

[0200] A flow-type production apparatus was assembled in the same manner as in Example 1. The sample solution was circulated while irradiating it with ultraviolet light (>300 nm) at a flow rate of 20 mL / min. The reaction was monitored by GC and terminated 180 minutes later, when the raw material conversion rate reached 99%. In this example, this means that the reaction was nearly completed after 36 cycles. The results of measuring the raw material conversion rate over time are shown in Table 8.

[0201] [Table 8]

[0202] The resulting reaction solution was washed with sodium thiosulfate and water, and then salted out. Next, sodium sulfate was added to the mixture, and the mixture was dried and concentrated. The concentrate was purified using a silica gel column using hexane as a developing solvent, and then dried under reduced pressure to obtain 795 mg (70% yield) of solid benzodithiophene.

[0203] In Example 5, where the raw material concentration was 30 mM, the yield was 83%, but in Example 6, where the raw material concentration was increased to 60 mM, the yield was slightly reduced to 70%.

[0204] [Example 9] (Circulation flow synthesis of benzodithiophene: flow rate 20 mL / min, raw material concentration 10 mM x 6 / iodine 0.1 eq) A 100 mL three-necked flask was charged with 193 mg (1 mmol) of 1,2-bis(thiophen-2-yl)ethene and 25.0 mg (0.1 mmol) of iodine, and the mixture was dissolved in 100 mL of toluene to prepare a sample solution.

[0205] A flow-type production apparatus was assembled in the same manner as in Example 1. The sample solution was circulated while irradiating it with ultraviolet light (>300 nm) at a flow rate of 20 mL / min. The reaction was monitored by gas chromatography. After confirming that the raw material had disappeared after 30 minutes, when the raw material conversion rate reached 99%, 193 mg (1 mmol) of 1,2-bis(thiophen-2-yl)ethene was added, and the sample solution was again circulated while irradiating it with ultraviolet light (>300 nm) at a flow rate of 20 mL / min. After confirming that the raw material had disappeared after 30 minutes, the process of adding additional raw material, irradiating it with light, and circulating it was repeated four more times (a total of five additional raw material additions).

[0206] The resulting reaction solution was washed with sodium thiosulfate and water, and then salted out. Next, sodium sulfate was added to dry the solution, and the solution was concentrated. After concentration, the solution was purified using a silica gel column using hexane as a developing solvent, and then dried under reduced pressure to obtain 478 mg (yield 83%) of solid benzodithiophene.

[0207] The results of Examples 1 to 9 are summarized in Table 9. The reaction times in Table 9 indicate the reaction times at which the raw material conversion rate is 98% or more.

[0208] [Table 9]

[0209] Regarding the reaction times in the production methods of Examples 1 to 9, when the flow rate and raw material concentration were taken into consideration and the time point at which the raw material conversion rate reached 98% or more was compared, the reaction times were approximately the same in all Examples. In particular, as is clear from the comparison between Example 1 and Example 2 as described above, when Example 2 was carried out at a flow rate twice that of Example 1, not only was the reaction time shortened, but the yield was also the same, and the productivity of benzodithiophene was significantly improved.

[0210] On the other hand, it was found that the yield could be improved by adding the raw material in portions.

[0211] Specifically, as is clear from a comparison between Example 3 and Example 4, the yield improved from 83% to 88% by adding the raw material at a concentration of 20 mM in two separate additions (adding the raw material once).

[0212] Furthermore, as is clear from a comparison between Example 5 and Example 6, the yield improved from 83% to 88% by adding the raw material at a concentration of 30 mM in three separate additions (adding the raw material twice).

[0213] Furthermore, as is clear from a comparison between Example 8 and Example 9, the yield was significantly improved from 70% to 90% by adding the raw material at a concentration of 60 mM in six separate additions (adding the raw material five times).

[0214] [Example 10] (Circulating flow synthesis of benzodithiophene: flow rate 20 mL / min, raw material concentration 10 mM x 3 / iodine 0.1 eq, large-volume synthesis) A 2000 mL three-neck flask was charged with 3.00 g (15.6 mmol) of 1,2-bis(thiophen-2-yl)ethene and 0.393 mg (1.55 mmol) of iodine, and the mixture was dissolved in 1500 mL of toluene to obtain a sample solution.

[0215] A flow-type production apparatus was assembled in the same manner as in Example 1. The sample solution was circulated at a flow rate of 20 mL / min while irradiating it with ultraviolet light (>300 nm). The reaction was monitored by GC, and it was confirmed that the raw material conversion rate reached 99.6% after 570 minutes. The results of measuring the raw material conversion rate over time are shown in Table 10.

[0216] [Table 10]

[0217] As is clear from Table 10, the raw material conversion rate was 98.5% after 450 minutes, which means that the reaction was nearly completed around the 90th cycle.

[0218] After 570 minutes, the raw material had disappeared. 3.00 g (15.6 mmol) of 1,2-bis(thiophen-2-yl)ethene was added, and the sample solution was circulated again at a flow rate of 20 mL / min while irradiating the sample solution with UV light (>300 nm). The reaction was monitored by GC, and after 630 minutes, the raw material conversion rate reached 99.3%. The results of measuring the raw material conversion rate over time are shown in Table 11.

[0219] [Table 11]

[0220] As is clear from Table 11, the raw material conversion rate was 98.1% after 480 minutes, which means that the reaction was nearly completed around the 96th cycle.

[0221] After 630 minutes, the raw material had disappeared. 3.00 g (15.6 mmol) of 1,2-bis(thiophen-2-yl)ethene was added, and the sample solution was circulated again at a flow rate of 20 mL / min while irradiating the sample solution with UV light (>300 nm). The reaction was monitored by GC, and after 600 minutes, the raw material conversion rate was confirmed to be 99.5%. The results of measuring the raw material conversion rate over time are shown in Table 12.

[0222] [Table 12]

[0223] As is clear from Table 12, the raw material conversion rate was 98.2% after 420 minutes, which means that the reaction was nearly completed around the 84th cycle.

[0224] The resulting reaction solution was washed with sodium thiosulfate and water, followed by salting out. Next, sodium sulfate was added to the mixture, which was then dried and concentrated. The concentrate was purified using a silica gel column using hexane as the developing solvent, and then dried under reduced pressure to obtain 8.33 g (yield 94%) of solid benzodithiophene.

[0225] Although benzodithiophene was obtained in high yield, as is clear from Tables 10 to 12, once the raw material conversion rate exceeded 90%, the relative concentration of the raw materials decreased, and the reaction progress tended to slow down. The reaction time was 27 hours, and the total reaction time until the raw material conversion rate reached 98% was 22.5 hours. [Example 11] (Recycling flow synthesis of benzodithiophene: flow rate 20 mL / min, raw material concentration 10 mM x 3 / iodine 0.1 eq, large-volume synthesis, purification after each cycle) A 2000 mL three-neck flask was charged with 3.00 g (15.6 mmol) of 1,2-bis(thiophen-2-yl)ethene and 0.393 mg (1.55 mmol) of iodine, and the mixture was dissolved in 1500 mL of toluene to obtain a sample solution.

[0226] A flow-type production apparatus was assembled in the same manner as in Example 1. The sample solution was circulated while irradiating it with UV light (>300 nm) at a flow rate of 20 mL / min. While monitoring the reaction by GC, when the raw material conversion rate reached 90% or more, the sample solution was poured out while irradiating it with UV light at a flow rate of 20 mL / min and filtered through a silica gel column approximately 1 cm in length. After filtration, 3.00 g (15.6 mmol) of 1,2-bis(thiophen-2-yl)ethene was added, and the sample solution was again irradiated with UV light (>300 nm) at a flow rate of 20 mL / min while circulating. When the raw material conversion rate reached 90% or more, additional raw material was added in the same manner, and the solution was again irradiated with light and circulated. Furthermore, when the raw material conversion rate reached 90% or more, a second additional raw material was added in the same manner, and the solution was again irradiated with light and circulated (a total of two additional raw material additions).

[0227] The resulting reaction solution was washed with sodium thiosulfate and water, and then salted out. Next, sodium sulfate was added to dry the solution, and the solution was concentrated. After concentration, the solution was purified using a silica gel column using hexane as a developing solvent, and then dried under reduced pressure to obtain 8.51 g (yield 96%) of solid benzodithiophene.

[0228] Compared to the manufacturing method of Example 10, the yield was slightly improved by stopping the reaction with the starting material earlier and purifying it with a silica gel column. In addition, the reaction time was 18.75 hours, which was significantly shorter than that of Example 10.

[0229] [Example 12] (Circulation flow synthesis of dinaphthothiophene: flow rate 20 mL / min, raw material concentration 1 mM / iodine 0.12 eq, epoxybutane, toluene)

[0230] [ka]

[0231] Into a 100 mL four-neck flask, 28.6 mg (0.1 mmol) of bis(2-naphthyl) sulfide and 30.9 mg (0.12 mmol) of iodine were placed and dissolved in 100 mL of toluene.

[0232] To the resulting solution, 758 mg (10.5 mmol) of 1,2-epoxybutane was added under a nitrogen atmosphere to prepare a sample solution.

[0233] A flow-type production apparatus was assembled in the same manner as in Example 1. The sample solution was circulated at room temperature for 120 minutes while irradiating it with ultraviolet light (>300 nm) at a flow rate of 20 mL / min. Because the color of the iodine had disappeared, 7.46 mg (0.03 mmol) of iodine was added. After the addition, the sample solution was again circulated while irradiating it with ultraviolet light (>300 nm) at a flow rate of 20 mL / min. The color of the iodine disappeared again 30 minutes after the addition. The raw material conversion rate was measured over time, and the results are shown in Table 13.

[0234] [Table 13]

[0235] The resulting reaction solution was washed with sodium thiosulfate and water, and then salted out. Next, sodium sulfate was added to the mixture, and the mixture was dried and concentrated. The concentrate was purified using a silica gel column using hexane as the developing solvent, and then dried under reduced pressure to obtain 20.7 mg (73% yield) of solid dinaphthothiophene.

[0236] [Example 13] (Circulating flow synthesis of dinaphthothiophene: flow rate 20 mL / min, raw material concentration 1 mM / iodine 0.12 eq, epoxybutane, cyclohexane)

[0237] [ka]

[0238] A 100 mL four-neck flask was charged with 28.6 mg (0.100 mmol) of bis(2-naphthyl) sulfide and 30.5 mg (0.12 mmol) of iodine, and the mixture was dissolved in 100 mL of cyclohexane to prepare a sample solution.

[0239] To the resulting solution, 727 mg (10.1 mmol) of 1,2-epoxybutane was added under a nitrogen atmosphere to prepare a sample solution.

[0240] A flow-type production apparatus was assembled in the same manner as in Example 1. The sample solution was circulated at room temperature for 240 minutes while irradiating it with ultraviolet light (>300 nm) at a flow rate of 20 mL / min. The raw material conversion rate was measured over time, and the results are shown in Table 14.

[0241] [Table 14]

[0242] The resulting reaction solution was washed with sodium thiosulfate and water, and then salted out. Next, sodium sulfate was added to the mixture, and the mixture was dried and concentrated. The concentrate was purified using a silica gel column using hexane as a developing solvent, and then dried under reduced pressure to obtain 22.9 mg (81% yield) of solid dinaphthothiophene.

[0243] Compared to Example 12, the yield was improved by using cyclohexane as a solvent.

[0244] [Example 14] (Circulating flow synthesis of phenanthrene: flow rate 20 mL / min, raw material concentration 10 mM / iodine 0.13 eq)

[0245] [ka]

[0246] A 100 mL three-necked flask was charged with 185 mg (1 mmol) of stilbene and 33.2 mg (0.13 mmol) of iodine, and the mixture was dissolved in 100 mL of toluene to prepare a sample solution.

[0247] A flow-type production apparatus was assembled in the same manner as in Example 1. The sample solution was circulated at a flow rate of 20 mL / min while being irradiated with ultraviolet light (>300 nm). The reaction was monitored by GC and terminated 210 minutes later when the raw material conversion rate reached 99.8%.

[0248] The resulting reaction solution was washed with sodium thiosulfate and water, and then salted out. Next, sodium sulfate was added to dry the solution, and the solution was concentrated. After concentration, the solution was purified using a silica gel column using hexane as a developing solvent, and then dried under reduced pressure to obtain 149 mg of solid phenanthrene (yield 81%).

[0249] [Example 15] (Circulation flow synthesis of 3,6-dimethylphenanthrene: flow rate 20 mL / min, raw material concentration 10 mM / iodine 0.1 eq)

[0250] [ka]

[0251] A 100 mL three-necked flask was charged with 208 mg (1 mmol) of dimethylstilbene and 25.3 mg (0.1 mmol) of iodine, and the mixture was dissolved in 100 mL of toluene to prepare a sample solution.

[0252] A flow-type production apparatus was assembled in the same manner as in Example 1. The sample solution was circulated at a flow rate of 20 mL / min while being irradiated with ultraviolet light (>300 nm). The reaction was monitored by GC and terminated 180 minutes later when the raw material conversion rate reached 99.9% or higher.

[0253] The resulting reaction solution was washed with sodium thiosulfate and water, and then salted out. Next, sodium sulfate was added to dry the solution, and the solution was concentrated. After concentration, the solution was purified using a silica gel column using hexane as a developing solvent, and then dried under reduced pressure to obtain 139 mg of solid 3,6-dimethylphenanthrene (yield 67%).

[0254] [Example 16] (Recycling flow synthesis of 3,6-dibromophenanthrene: flow rate 20 mL / min, raw material concentration 10 mM / iodine 0.1 eq)

[0255] [ka]

[0256] A 100 mL three-necked flask was charged with 339 mg (1 mmol) of dibromostilbene and 25.7 mg (0.1 mmol) of iodine, and the mixture was dissolved in 100 mL of toluene to prepare a sample solution.

[0257] A flow-type production apparatus was assembled in the same manner as in Example 1. The sample solution was circulated at a flow rate of 20 mL / min while being irradiated with ultraviolet light (>300 nm). The reaction was monitored by GC and terminated 90 minutes later when the raw material conversion rate reached 99.9%.

[0258] The resulting reaction solution was washed with sodium thiosulfate and water, and then salted out. Next, sodium sulfate was added to dry the solution, and the solution was concentrated. After concentration, the solution was purified using a silica gel column using hexane as a developing solvent, and then dried under reduced pressure to obtain 178 mg (yield 51%) of solid 3,6-dibromophenanthrene.

[0259] [Example 17] (Circulating flow synthesis of 8-bromonaphtho[2,1-b]thiophene: flow rate 20 mL / min, starting material concentration 10 mM / iodine 0.1 eq)

[0260] [ka]

[0261] A 100 mL three-necked flask was charged with 268 mg (1 mmol) of bromophenylthiophenylethene and 24.8 mg (0.1 mmol) of iodine, and the mixture was dissolved in 100 mL of toluene to prepare a sample solution.

[0262] A flow-type production apparatus was assembled in the same manner as in Example 1. The sample solution was circulated at a flow rate of 20 mL / min while being irradiated with ultraviolet light (>300 nm). The reaction was monitored by GC and terminated 120 minutes later when the raw material conversion rate reached 99.9%.

[0263] The resulting reaction solution was washed with sodium thiosulfate and water, followed by salting out. Sodium sulfate was then added to the mixture, which was then dried and concentrated. The concentrate was then purified using a silica gel column with hexane as the developing solvent, and then dried under reduced pressure to obtain 173 mg (65% yield) of solid 8-bromonaphtho[2,1-b]thiophene. [Industrial Applicability]

[0264] The manufacturing method of the present invention can be used as a method for producing photoreaction products manufactured by flow synthesis, and is particularly useful as a method for producing photocyclides. [Explanation of symbols]

[0265] 1… Apparatus for producing photoreaction products 2…Storage tank unit 2a…Reacted liquid 3…Introduction Line 3a...Inlet 4…Means of liquid delivery 5…Reaction Unit 5a... Reaction line 5b…Light source section 5b1…Light source 5b2...Water-cooled jacket 5b3…Cooler 6…Circulation line 7…Analysis means

Claims

1. A method for producing photoreaction products by flow synthesis, A reaction step in which light is irradiated onto a reaction solution containing raw materials while flowing through a reaction channel to obtain a reaction solution containing the photoreaction product and unreacted raw materials, A method for producing a photoreaction product, comprising a circulation step for returning the reaction solution to the reaction channel as a new reactant and circulating it, and repeating the reaction step.

2. The manufacturing method according to claim 1, wherein in the reaction step, the flow rate of the liquid to be reacted is 50 mm / second or more in linear velocity.

3. The manufacturing method according to claim 1 or 2, wherein the concentration of the raw material in the reaction solution is 100 mM or less.

4. The manufacturing method according to claim 1 or 2, wherein the raw material concentration of the first reaction solution containing the starting raw materials is 100 mM or less, and after the start of the reaction, new raw materials are added in a range such that the concentration of unreacted raw materials in the reaction solution does not exceed 100 mM.

5. The manufacturing method according to claim 1 or 2, further comprising a purification step of purifying the reaction solution.

6. The manufacturing method according to claim 5, wherein the reaction solution purified in the purification step is returned to the reaction channel as a new reaction solution.

7. The method for producing the photoreaction product according to claim 1 or 2, wherein the photoreaction product is a cyclic compound.

8. The method for producing the photoreaction product according to claim 1 or 2, wherein the photoreaction product is a condensed polycyclic compound.

9. A manufacturing apparatus for producing photoreaction products by flow synthesis, A reaction unit comprising a light source and a reaction channel, wherein light is irradiated onto a reaction liquid containing raw materials while the reaction channel is flowing, in order to obtain a reaction liquid containing the photoreaction product and unreacted raw materials, A circulation line for returning the reaction solution to the reaction channel as a new reactant and circulating it, and for repeating the reaction in the reaction unit, A manufacturing apparatus including a liquid delivery means for circulating the reaction solution.

10. The manufacturing apparatus according to claim 9, wherein the reaction channel is wound spirally along the outer circumference of the light source in the reaction unit.

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