Method for producing halocarbonyl compounds

Abstract

To provide a method for producing a halocarbonyl compound in good yield without requiring an expensive oxidizing agent or a metal salt which is feared to reside, while suppressing an amount of use of a halogen cation source.SOLUTION: There is provided a method for producing a halocarbonyl compound, including a reaction step of electrolytically reacting a cyclic compound represented by the following formula (1) in a solution containing a halide salt and an ammonium salt to obtain a halocarbonyl compound represented by the following formula (1'). The cyclic compound represented by the following formula (1) is a compound having a ring A having a hydroxy group and R1. In the formula (1) or (1'), R1 represents hydrogen or a monovalent organic group; R2 represents an optionally substituted divalent hydrocarbon group having 2 to 12 carbon atoms, and the carbon atoms constituting the hydrocarbon group may be substituted with nitrogen, oxygen, or sulfur; and Z represents a halogen group.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a method for producing a halocarbonyl compound. [Background technology]

[0002] Halocarbonyl compounds are used in a wide range of fields for various purposes. For example, haloketone compounds are used as building blocks for various pharmaceuticals and pharmaceutical candidate compounds. In recent years, methods for producing halocarbonyl compounds have been widely investigated, and one of them is C(sp 3 )-C(sp 3 There is a production method that utilizes the regioselective oxidative cleavage of hydroxyl-containing cyclic compounds, such as cycloalkanols with a hydroxyl bond. This regioselective oxidative cleavage reaction is extremely important in organic synthetic chemistry because it enables diverse transformations of molecular structures. Conventional regioselective oxidative cleavage reactions of hydroxyl-containing cyclic compounds have utilized methods using molecular bromine or visible light. For example, Non-Patent Document 1 discloses a technique for electrochemical decomposition and chlorination of hydroxyl-containing cyclic compounds using a manganese catalyst, and Non-Patent Document 2 discloses a technique for cleaving hydroxyl-containing cyclic compounds by reacting them with a compound having an N-SCF bond. [Prior art documents] [Non-patent literature]

[0003] [Non-Patent Document 1] Benjamin DW Allen, et al., Organic Letters, 2019, 21, 92141-9246 [Non-patent document 2] Tengfei Ji, et al., Organic Letters, 2020, 22, 2579-2583 Summary of the Invention [Problem to be solved by the invention]

[0004] The ring-opening reaction of a hydroxy group-containing cyclic compound described in Non-Patent Documents 1 and 2 above has the problem of requiring a large excess of a halogen cation source, an expensive oxidizing agent, and a metal salt that may remain, and therefore there is room for improvement. Therefore, an object of the present invention is to provide a method for producing a halocarbonyl compound in a high yield while reducing the amount of a halogen cation source used and without requiring an expensive oxidizing agent or a metal salt that may remain. [Means for solving the problem]

[0005] As a result of extensive research into solving the above problems, the present inventors have found that the above problems can be solved by using a specific substance, and have thus completed the present invention.

[0006] That is, the gist of the present invention is as follows. [1] A method for producing a halocarbonyl compound, comprising a reaction step of electrolytically reacting a cyclic compound represented by the following formula (1) in a solution containing a halide salt and an ammonium salt to obtain a halocarbonyl compound represented by the following formula (1'): [ka] (The cyclic compound represented by the above formula (1) has a hydroxy group and R 1 and a divalent hydrocarbon group having 2 to 12 carbon atoms which may have a substituent and is bonded to the carbon, and the carbon constituting the hydrocarbon group may be substituted with nitrogen, oxygen, or sulfur, and R 1 and the divalent hydrocarbon group having 2 to 12 carbon atoms which may have a substituent, to form a ring; in the above formulas (1) and (1'), R 1 represents hydrogen or a monovalent organic group; R 2represents a divalent hydrocarbon group having 2 to 12 carbon atoms which may have a substituent, and a carbon atom constituting the hydrocarbon group may be substituted with nitrogen, oxygen, or sulfur; and Z represents a halogen group. [2] The method for producing a halocarbonyl compound according to [1], wherein the solution further contains a basic compound. [3] The method for producing a halocarbonyl compound according to [1] or [2], wherein the cyclic compound represented by formula (1) is at least one compound selected from the group of compounds represented by the following formulas (2) to (5), and the halocarbonyl compounds obtained by subjecting the cyclic compound to an electrolytic reaction are compounds represented by the following formulas (2') to (5'), respectively, for the compounds represented by the following formulas (2) to (5). [ka] (In the above formulas (2) to (5) and (2') to (5'), R 1 is R in the formula (1). 1 is synonymous with ;R 3 ~R 8 each independently represents hydrogen, a halogen group, or a monovalent organic group; X represents a single bond or a divalent hydrocarbon group having 1 to 9 carbon atoms which may have a substituent; wherein a carbon atom constituting the hydrocarbon group may be substituted with nitrogen, oxygen, or sulfur; W represents a trivalent hydrocarbon group having 1 to 9 carbon atoms which may have a substituent, wherein a carbon atom constituting the hydrocarbon group may be substituted with nitrogen, oxygen, or sulfur; Y represents a tetravalent hydrocarbon group having 2 to 9 carbon atoms which may have a substituent, wherein a carbon atom constituting the hydrocarbon group may be substituted with nitrogen, oxygen, or sulfur; Z has the same meaning as Z in formula (1') above; and in each formula, R 3 ~R 8 , X, and Y may be bonded to each other to form a ring; none of the compounds represented by formulas (2) to (5) and (2') to (5') has adjacent unsaturated bonds.) [4] The method for producing a halocarbonyl compound according to [3], wherein at least one compound selected from the group of compounds represented by the formulas (2) to (5) has a structure represented by any one of the following formulas (A-1) to (A-9), and a carbon or nitrogen constituting a ring in the structure has hydrogen or a monovalent organic group as a substituent. [ka] (In the above formulas (A-1) to (A-9), R 1 are independently R in the formula (1). 1 is equivalent to [5] The method for producing a halocarbonyl compound according to [4], wherein in the compound having a structure represented by any one of the formulae (A-1) to (A-9), the monovalent organic group that may be substituted on the carbon or nitrogen constituting the ring is an alkyl group having 1 to 12 carbon atoms. [6] The method for producing a halocarbonyl compound according to any one of [1] to [5], wherein the solution contains at least an organic solvent or water. [7] The method for producing a halocarbonyl compound according to [6], wherein the solution contains an organic solvent and water. [8] The method for producing a halocarbonyl compound according to any one of [1] to [7], wherein the halide salt is magnesium bromide, magnesium chloride, or magnesium iodide. [9] The method for producing a halocarbonyl compound according to any one of [1] to [8], wherein the basic substance is a hydroxide or a carbonate.

[10] The method for producing a halocarbonyl compound according to any one of [1] to [9], wherein the electrolytic reaction is carried out by irradiating with light in the reaction step. [Effects of the Invention]

[0007] According to the present invention, it is possible to provide a method for producing a halocarbonyl compound in a high yield, while reducing the amount of a halogen cation source used and without requiring an expensive oxidizing agent or a metal salt that may remain. DETAILED DESCRIPTION OF THE INVENTION

[0008] The following describes in detail the embodiments of the present invention, but these descriptions are examples (typical examples) of the embodiments of the present invention, and the present invention is not limited to these contents as long as it does not deviate from the gist of the invention. In this specification, a numerical range expressed using "to" means a range that includes the numerical values ​​written before and after "to" as the lower and upper limits, and "A to B" means A or more and B or less. In addition, in this specification, "plurality" means "two or more." In addition, in this specification, the term "independently" used when describing two or more objects together means that the two or more objects may be the same or different.

[0009] A method for producing a halocarbonyl compound according to one embodiment of the present invention (hereinafter also simply referred to as a "method for producing a halocarbonyl compound") is a method for producing a halocarbonyl compound, which comprises a reaction step of electrolytically reacting a cyclic compound represented by the following formula (1) (hereinafter also referred to as a "substrate") in a solution containing a halide salt and an ammonium salt to obtain a halocarbonyl compound represented by the following formula (1').

[0010] [ka]

[0011] The cyclic compound represented by the above formula (1) contains a hydroxy group and R 1 and a divalent hydrocarbon group having 2 to 12 carbon atoms which may have a substituent and is bonded to the carbon, and the carbon constituting the hydrocarbon group may be substituted with nitrogen, oxygen, or sulfur, and R 1 and the divalent hydrocarbon group having 2 to 12 carbon atoms which may have a substituent, to form a ring; in the above formulas (1) and (1'), R 1 represents hydrogen or a monovalent organic group; R 2represents a divalent hydrocarbon group having 2 to 12 carbon atoms which may have a substituent, and a carbon atom constituting the hydrocarbon group may be substituted with nitrogen, oxygen, or sulfur; and Z represents a halogen group. The divalent hydrocarbon group here may be linear, branched, or have a cyclic structure.

[0012] In this specification, the monovalent organic group refers to an alkyl group having 1 to 20 carbon atoms which may have a substituent, an alkenyl group having 1 to 20 carbon atoms which may have a substituent, an alkynyl group having 1 to 20 carbon atoms which may have a substituent, an alkoxy group having 1 to 20 carbon atoms which may have a substituent, -C≡N, -NR a R b R c , -C(=O)OH, -C(=O)OR', -C(=O)R', -SH, -SiR a R b R c , -BH2, -SeH, an optionally substituted monovalent aliphatic hydrocarbon ring group, an optionally substituted monovalent aromatic hydrocarbon ring group, an optionally substituted monovalent aromatic heterocyclic group, etc., and R', R a , R b , R c are independently hydrogen or an alkyl group having 1 to 20 carbon atoms which may have a substituent. In addition, in this specification, the substituent in the expression "may have a substituent" is a halogen group, an alkyl group having 1 to 20 carbon atoms, an alkenyl group having 1 to 20 carbon atoms, an alkynyl group having 1 to 20 carbon atoms, an alkoxy group having 1 to 20 carbon atoms, -C≡N, -NH3, -C(=O)OH, -C(=O)OR', -C(=O)R', -SH, -SiR a R b R c , -BH2, -SeH, monovalent aliphatic hydrocarbon ring group, monovalent aromatic hydrocarbon ring group, monovalent aromatic heterocyclic group R', R a , R b , R c are each independently hydrogen or an alkyl group having 1 to 20 carbon atoms.

[0013] <Cyclic compounds and halocarbonyl compounds> The cyclic compound represented by the above formula (1) is not particularly limited as long as it has the above structure, and by subjecting the cyclic compound to an electrolytic reaction in the presence of a halide salt and an ammonium salt, a regioselective oxidative cleavage reaction occurs, as shown in the following reaction, to produce a halocarbonyl compound represented by the above formula (1').

[0014] [ka]

[0015] The cyclic compound represented by formula (1) is a compound having a hydroxy group and R 1 and a divalent hydrocarbon group having 2 to 12 carbon atoms which may have a substituent and is bonded to the carbon, and the carbon constituting the hydrocarbon group may be substituted with nitrogen, oxygen, or sulfur, and R 1 and the divalent hydrocarbon group having 2 to 12 carbon atoms which may have a substituent. 1 and the optionally substituted divalent hydrocarbon group having 2 to 12 carbon atoms are bonded to each other, examples of the compound having ring A include 1-adamantanol. R in formulas (1) and (1′) 1 represents hydrogen or a monovalent organic group, and specifically may be hydrogen, or an alkyl group such as a methyl group, an ethyl group, a propyl group, an isopropyl group, an n-butyl group, a t-butyl group, an isobutyl group, a pentyl group, a hexyl group, a heptyl group, an octyl group, or an ethylhexyl group; R 1 From the viewpoint of preventing a side reaction due to unintended bromination to the above, it may preferably be hydrogen or a straight-chain alkyl group such as a methyl group, an ethyl group, a propyl group or an n-butyl group. R in formula (1') 2 represents a divalent hydrocarbon group having 2 to 12 carbon atoms which may have a substituent, and a carbon atom constituting the hydrocarbon group may be substituted with nitrogen, oxygen, or sulfur.

[0016] Z in formula (1') is determined depending on the type of halide salt and may be any of fluorine (F), chlorine (Cl), bromine (Br), or iodine (I). However, in view of the preferred embodiments of the halide salt described below, Z is preferably Cl, Br, or I, and particularly preferably Br.

[0017] The cyclic compound represented by formula (1) above is preferably at least one compound selected from the group of compounds represented by formulas (2) to (5) below, in view of its ease of availability and industrial usefulness, and the halocarbonyl compounds obtained by subjecting the cyclic compound to an electrolytic reaction are preferably compounds represented by formulas (2') to (5') below for the compounds represented by formulas (2) to (5) below. Specifically, by subjecting the compounds represented by formulas (2) to (5) below to an electrolytic reaction in the presence of a halide salt and an ammonium salt, a regioselective oxidative cleavage reaction occurs, producing the halocarbonyl compounds represented by formulas (2') to (5') below, respectively.

[0018] [ka]

[0019] In the above formulas (2) to (5) and (2') to (5'), R 1 R in the formula (1) including the preferred conditions. 1 is synonymous with. In the above formulas (2) to (5) and (2') to (5'), R 3 ~R 8 each independently represents hydrogen or a monovalent organic group, and specifically may be an alkyl group such as a methyl group, an ethyl group, a propyl group, an isopropyl group, an n-butyl group, a t-butyl group, an isobutyl group, a pentyl group, a hexyl group, a heptyl group, an octyl group, or an ethylhexyl group; a cyclic alkyl group having 3 to 12 carbon atoms; an aromatic group such as a phenyl group or a naphthyl group; a carbonyl group, a nitro group, a sulfo group, or a phosphonium group; and R 3 ~R 8From the viewpoint of preventing a side reaction due to unintended bromination to the above, it may preferably be hydrogen or a straight-chain alkyl such as a methyl group, an ethyl group, a propyl group, or an n-butyl group. In the above formulas (2) and (2'), X represents a single bond or a divalent hydrocarbon group having 1 to 9 carbon atoms which may have a substituent, and the carbon atoms constituting the hydrocarbon group may be substituted with nitrogen, oxygen, or sulfur. In the above formulas (2) to (3) and (2') to (3'), W represents a trivalent hydrocarbon group having 1 to 9 carbon atoms which may have a substituent, and a carbon atom constituting the hydrocarbon group may be substituted with nitrogen, oxygen, or sulfur; In the above formulas (5) and (5'), Y represents a tetravalent hydrocarbon group having 2 to 9 carbon atoms which may have a substituent, and the carbon atoms constituting the hydrocarbon group may be substituted with nitrogen, oxygen, or sulfur. In (2') to (5'), Z has the same meaning as Z in the formula (1') above, including suitable conditions. In addition, in each formula, R 3 ~R 8 , X, and Y may be bonded to each other to form a ring. Furthermore, none of the compounds represented by formulas (2) to (5) and (2') to (5') has adjacent unsaturated bonds. Furthermore, the hydrocarbon groups in X, Y, and Z may be straight-chain, may have a branched chain, or may have a cyclic structure.

[0020] At least one compound selected from the group of compounds represented by the above formulas (2) to (5) preferably has a structure represented by the following formulas (A-1) to (A-9), and is a compound in which the carbon or nitrogen constituting the ring in the structure (the ring represented in the formula) has hydrogen or a monovalent organic group as a substituent.

[0021] [ka]

[0022] In the above formulas (A-1) to (A-9), R 1is R in the above formula (1), including the preferred conditions. 1 is synonymous with. In addition, in the compounds having the structures represented by the above formulas (A-1) to (A-7), the monovalent organic group that may be substituted on the carbon or nitrogen constituting the ring represented by the formula is preferably an alkyl group having 1 to 12 carbon atoms, from the viewpoint of preventing a decrease in purity due to side reactions of the organic group.

[0023] From the viewpoints of availability and industrial usefulness, the group of compounds having structures represented by the above formulas (A-1) to (A-9) is preferably the group of compounds represented by (A-1), (A-2), (A-6), or (A-7), and more specifically, the group of compounds represented by the following formulas (B-1) to (B-5) is preferred.

[0024] [ka]

[0025] In the above formulas (B-1) to (B-5), the carbon atoms constituting the rings represented by the formulas may be substituted with an alkyl group having 1 to 12 carbon atoms, and R 9 is a group selected from an alkyl group having 1 to 12 carbon atoms, a phenyl group, a trihalogenomethyl group, and a cyano group. 9 The hydrogen atoms at positions 2 to 5 of the benzene ring of the phenyl group in the formula (I) may be substituted with a methyl group, an ethyl group, a propyl group, a butyl group, a methoxy group, an ethoxy group, a fluorine atom, a chlorine atom, an iodine atom, or a 2-naphthyl group. 9 is a phenyl group, and one of the hydrogen atoms at positions 2 to 5 of the benzene ring of the phenyl group may be substituted with a methyl group, an ethyl group, a propyl group, or a butyl group.

[0026] The method for producing the cyclic compound represented by the above formula (1) is not particularly limited, and it can be produced by using a known method, or a commercially available product can also be used. A specific production method includes, for example, dissolving a cycloalkanone in a solvent such as tetrahydrofuran, adding a halogenated aryl metal compound, further adding an aqueous ammonium chloride solution, extracting with ethyl acetate, and purifying the organic layer.

[0027] <Reaction process> The method for producing a halocarbonyl compound according to this embodiment includes a reaction step of subjecting a cyclic compound represented by the above formula (1) to an electrolytic reaction (hereinafter also simply referred to as "reaction") in a solution containing a halide salt and an ammonium salt to obtain a halocarbonyl compound represented by the above formula (1'). The reaction mode in the reaction step is not particularly limited, but can be carried out under the following conditions.

[0028] The method for carrying out the electrolytic reaction is not particularly limited, and known methods can be applied. For example, the electrolytic reaction can be carried out by using a membrane-less cell as a reaction vessel, placing a solution containing the cyclic compound represented by the above formula (1), a halide salt, and an ammonium salt in the membrane-less cell, immersing a pair of electrodes in the solution, and passing a current between the electrodes. The size of the reaction vessel is not particularly limited. For example, the volume may be 0.1 cm 3 More than 10,000cm 3 It may be less than 0.5cm 3 Over 1,000cm 3 The material is not particularly limited and known materials can be used. The type of electrode is not particularly limited. For example, the anode (cathode) may be made of gold, platinum, or graphite. For the cathode (anode), gold, platinum, zinc, iron, nickel, molybdenum, copper, or the like can be used. Specific combinations of [cathode:anode] include [zinc:platinum], [gold:platinum], [iron:platinum], [nickel:platinum], [copper:platinum], [platinum:platinum], [graphite:platinum], [platinum:graphite], or [graphite:graphite]. In particular, from the viewpoint of improving yield, the combinations of [zinc:platinum], [platinum:platinum], or [graphite:platinum] are preferred, and the combinations of [zinc:platinum] or [platinum:platinum] are more preferred, and the combination of [zinc:platinum] is even more preferred. The area of ​​the electrode is not particularly limited and may be selected appropriately depending on the volume of the reaction vessel and the solvent to be reacted. For example, 2 Over 5,000cm 2 Less than or equal to 1 cm 2 Over 1,000cm 2 It may be less than 1 cm 2 More than 200cm 2 The following may also be used. The current flowing between the pair of electrodes is not particularly limited. For example, the current density per unit area is 0.1 mA / cm. 2 More than 1,000mA / cm 2 It may be less than 1mA / cm 2 More than 500mA / cm 2 The following may also be used. The total charge amount in the electrolytic reaction is not particularly limited, and may be, for example, 96,500 coulombs or more and 500,000 coulombs or less, 110,000 coulombs or more and 400,000 coulombs or less, or 193,000 coulombs or more and 400,000 coulombs or less, per mole of the cyclic compound of this embodiment.

[0029] The reaction temperature is not particularly limited, but from the viewpoint of maintaining the solubility of the substrate in the solvent and suppressing evaporation of the solvent, it is usually -20°C or higher, preferably -10°C or higher, more preferably -5°C or higher, even more preferably -1°C or higher, and particularly preferably 0°C or higher, and is usually 100°C or lower, preferably 80°C or lower, more preferably 60°C or lower, even more preferably 40°C or lower, and particularly preferably 20°C or lower. The reaction time is not particularly limited and can be set appropriately depending on the amount of reaction solution. It is usually 5 minutes or more, preferably 10 minutes or more, more preferably 20 minutes or more, even more preferably 40 minutes or more, and particularly preferably 60 minutes or more, and is usually 1,000 minutes or less, preferably 600 minutes or less, more preferably 300 minutes or less, even more preferably 180 minutes or less, and particularly preferably 120 minutes or less. From the viewpoint of improving the yield of the target substance, the reaction is preferably carried out by irradiating light. The type and intensity of light are not particularly limited, and examples of the type of light that can be used include microwaves, infrared rays, visible light, ultraviolet rays, and X-rays. From the viewpoint of improving the reaction efficiency, it is preferable to use visible light or ultraviolet rays. In addition, the intensity of light (radiant intensity, unit: Jm -2 s -1 ) is, for example, 0.1 Jm -2 s -1 Over 500Jm -2 s -1 It may be less than 1 Jm -2 s -1 W or more, 100Jm -2 s -1 For reference, the radiant intensity of a room illuminated by fluorescent lamps is 2.2 J / m -2 s -1 , 440Jm under direct sunlight at midday -2 s -1 is.

[0030] The solution is not particularly limited as long as it contains at least the cyclic compound represented by the above formula (1), a halide salt, and an ammonium salt, and further contains a solvent, and may also contain other components, particularly a basic compound, from the viewpoint of promoting the reaction. The content of the cyclic compound represented by the above formula (1) in the solution is not particularly limited, but from the viewpoint of efficiently promoting the reaction on the electrode surface, it is usually 0.1 mol / L by weight or more, preferably 1 mol / L or more, more preferably 3 mol / L or more, even more preferably 5 mol / L or more, and particularly preferably 10 mol / L or more, and is usually 10 mol / L or less, preferably 8 mol / L or less, more preferably 6 mol / L or less, and even more preferably 5 mol / L or less. It is preferable that the concentration is 3 mol / L or less, and particularly preferable that the concentration is 3 mol / L or less. The cyclic compound represented by the above formula (1) contained in the solution is not limited to one type, and may contain two or more types.

[0031] The halide salt contained in the solution is not particularly limited as long as it is a salt containing a halogen, and may be an inorganic salt or an organic salt, but from the viewpoint of improving the reaction efficiency, it is preferably an inorganic salt. The type of halogen used in the halide salt is not particularly limited and may be any of F, Cl, Br, or I. From the viewpoint of improving the reaction efficiency, however, Cl, Br, or I is preferred, and Br is particularly preferred. Examples of inorganic salts include halide salts of sodium, potassium, calcium, magnesium, aluminum, zinc, etc., and from the viewpoint of improving reaction efficiency, halide salts of magnesium, sodium, potassium, and calcium are preferred, and magnesium salts are particularly preferred, specifically magnesium bromide, magnesium chloride, and magnesium iodide are preferred. From the viewpoint of cost reduction and safety, it is preferable that the metal element that becomes the cation does not contain a heavy metal. Examples of heavy metals include Fe, Pb, Au, Pt, Ag, Cu, Cr, Cd, Hg, Zn, As, Mn, Co, Ni, Mo, W, Sn, Bi, U, Pu, etc., and the content of heavy metals in the solution is 1×10 -3 mol / L or less, and preferably 1×10 -6 mol / L or less is more preferable, and 1×10 -7 It is more preferable that the concentration is 0 mol / L or less, and it is more preferable that the concentration is substantially 0 mol / L (below the detection limit). Examples of organic salts include salts of tetraalkylammonium, such as tetramethylammonium, tetraethylammonium, and tetrabutylammonium, in which the alkyl group has 1 to 10 carbon atoms, with F, Cl, Br, or I. Specific examples include tetramethylammonium chloride, tetramethylammonium bromide, tetramethylammonium iodide, tetraethylammonium chloride, tetraethylammonium bromide, tetraethylammonium iodide, tetrabutylammonium chloride, tetrabutylammonium bromide, and tetrabutylammonium iodide. The content of the halide salt in the solution is not particularly limited, but from the viewpoint of efficiently proceeding with the reaction, it is usually 0.001 mol / L or more, preferably 0.01 mol / L or more, more preferably 0.1 mol / L or more, even more preferably 0.4 mol / L or more, and particularly preferably 0.8 mol / L or more, and is usually 10 mol / L or less, preferably 6 mol / L or less, more preferably 4 mol / L or less, even more preferably 3 mol / L or less, and particularly preferably 2 mol / L or less. In the solution, the molar ratio of the halide salt to the cyclic compound represented by the above formula (1) is not particularly limited, but from the viewpoint of improving the reaction efficiency, it is usually 0.2 or more, preferably 0.5 or more, more preferably 0.6 or more, even more preferably 0.7 or more, and also usually 0.8 or more, preferably 0.9 or more, more preferably 0.95 or more, even more preferably 1 or more. The halide salt contained in the solution is not limited to one type, and may contain two or more types.

[0032] The solution further contains an ammonium salt as a phase transfer catalyst. A phase transfer catalyst is a substance used to react a water-insoluble organic compound with an organic solvent-insoluble reagent. As used herein, ammonium salt does not include the above-mentioned halide salts. The type of ammonium salt is not particularly limited, but from the viewpoint of improving the reaction efficiency, it is preferable to use a salt of tetraalkylammonium and a hydrophobic anion. The hydrophobic anion may be an organic acid ion such as acetate ion or lactate ion, or a borate ion such as tetrafluoroborate or tetraphenylborate. However, when a salt is formed with ammonium, the correlation between the anion and the salt is different. From the viewpoint of performance as a catalytic converter, organic acid ions and borate ions are generally used. Specific examples of ammonium salts include tetramethylammonium tetrafluoroborate, tetraethylammonium tetrafluoroborate, tetrabutylammonium tetrafluoroborate, tetramethylammonium tetraphenylborate, tetraethylammonium tetraphenylborate, and tetrabutylammonium tetraphenylborate. From the viewpoint of improving reaction efficiency, tetramethylammonium tetrafluoroborate is preferred. Ammonium salts used in phase transfer catalysts are generally salts of tetraalkylammonium and hydrophobic anions. Examples of hydrophobic ions include organic acid ions such as hydroxide ions, acetate ions, and lactate ions, and borate ions such as tetrafluoroborate and tetraphenylborate. From the viewpoint of the performance as a phase transfer catalyst when forming a salt with ammonium, organic acid ions and borate ions are generally used. Specific examples of ammonium salts include tetramethylammonium hydroxide, tetraethylammonium hydroxide, tetrabutylammonium hydroxide, tetramethylammonium tetrafluoroborate, tetraethylammonium tetrafluoroborate, tetrabutylammonium tetrafluoroborate, tetramethylammonium tetraphenylborate, tetraethylammonium tetraphenylborate, and tetrabutylammonium tetraphenylborate. However, from the viewpoint of improving reaction efficiency, tetramethylammonium tetrafluoroborate is preferred. The solution may also contain a phase transfer catalyst other than the above ammonium salts, such as a phosphonium salt. The content of the phase transfer catalyst (particularly ammonium salt) in the solution is not particularly limited, but from the viewpoint of efficiently proceeding with the reaction, it is usually 0.01% by weight or more, preferably 0.05% by weight or more, more preferably 0.1% by weight or more, even more preferably 0.2% by weight or more, and particularly preferably 0.5% by weight or more, and is usually 20% by weight or less, preferably 15% by weight or less, more preferably 10% by weight or less, even more preferably 7% by weight or less, and particularly preferably 5% by weight or less. The phase transfer catalyst contained in the solution is not limited to one type, and may contain two or more types.

[0033] The solution may contain a basic compound, the type of which is not particularly limited, and examples thereof include hydroxides, carbonates, bicarbonates, and nitrates of lithium, sodium, potassium, calcium, and magnesium. However, from the viewpoint of improving reaction efficiency, hydroxides or carbonates are preferred. Specific examples of the basic compound include lithium hydroxide, sodium hydroxide, potassium hydroxide, calcium hydroxide, magnesium hydroxide, lithium carbonate, sodium carbonate, potassium carbonate, calcium carbonate, and magnesium carbonate. Note that the basic compound in this specification does not include the above-mentioned halide salts and ammonium salts. The content of the basic compound in the solution is not particularly limited, but from the viewpoint of efficiently proceeding with the reaction, it is usually 0.01 mol / L or more, preferably 0.05 mol / L or more, more preferably 0.1 mol / L or more, even more preferably 0.15 mol / L or more, and particularly preferably 0.2 mol / L or more, and is usually 3.5 mol / L or less, preferably 3 mol / L or less, more preferably 2.5 mol / L or less, even more preferably 2 mol / L or less, and particularly preferably 1.5 mol / L or less. In the solution, the molar ratio of the basic compound to the cyclic compound represented by the above formula (1) is not particularly limited, but from the viewpoint of improving the reaction efficiency, it is usually 0.01 or more, preferably 0.05 or more, more preferably 0.1 or more, even more preferably 0.2 or more, and usually 0.5 or more, preferably 0.6 or more, more preferably 0.8 or more, even more preferably 1 or more. The basic compound contained in the solution is not limited to one type, and may contain two or more types.

[0034] The type of solvent contained in the solution is not particularly limited, and may be an organic solvent or an inorganic solvent, and one type may be used alone, or two or more types may be used in combination. Examples of the organic solvent include alcohol solvents, ether solvents, ester solvents, ketone solvents, aromatic solvents, nitrile solvents, and chlorine solvents, among which ester solvents, nitrile solvents, and ether solvents are preferred from the viewpoint of improving the reaction efficiency, and ester solvents are particularly preferred. Specific examples of the organic solvent include methyl acetate, ethyl acetate, acetone, tetrahydrofuran, and acetonitrile, among which methyl acetate and ethyl acetate are preferred from the viewpoint of the reaction efficiency. Examples of inorganic solvents include water, nitric acid, ammonia, ionic liquids such as salts of imidazolium cations and PF anions, hydrogen peroxide, carbon disulfide, and carbon tetrachloride. From the viewpoint of improving the stability of the compound in the solution and the reaction efficiency, water and ammonium salts are preferred, and water is particularly preferred. When two or more solvents are used in combination, the solvent preferably contains an organic solvent and water, from the viewpoint of improving the reaction efficiency. The content of the solvent in the solution is not particularly limited, but from the viewpoint of imparting conductivity to the solution and efficiently promoting the reaction, it is usually 5% by weight or more, preferably 10% by weight or more, more preferably 30% by weight or more, even more preferably 40% by weight or more, and particularly preferably 50% by weight or more, and is usually 99.9% by weight or less, preferably 99.5% by weight or less, more preferably 99.0% by weight or less, even more preferably 98.5% by weight or less, and particularly preferably 98% by weight or less. Furthermore, the content of the organic solvent in the solution is not particularly limited, but from the viewpoint of efficiently proceeding with the reaction, it is usually 1% by volume or more, preferably 4% by volume or more, more preferably 6% by volume or more, even more preferably 8% by volume or more, and particularly preferably 10% by volume or more, and is usually 99% by weight or less, preferably 95% by volume or less, more preferably 90% by volume or less, even more preferably 85% by volume or less, and particularly preferably 80% by volume or less. Furthermore, the water content in the solution is not particularly limited, but from the viewpoint of efficiently proceeding with the reaction, it is usually 1% by volume or more, preferably 5% by volume or more, more preferably 10% by volume or more, even more preferably 15% by volume or more, and particularly preferably 20% by volume or more, and is usually 99% by volume or less, preferably 97% by volume or less, more preferably 95% by volume or less, even more preferably 92% by volume or less, and particularly preferably 90% by volume or less.

[0035] The solution may contain components (other components) other than the above components, such as a pH adjuster, which can be used appropriately depending on the types of raw materials used and reaction conditions. Examples of pH adjusters include monosodium dihydrogen phosphate, disodium hydrogen phosphate, potassium dihydrogen phosphate, dipotassium hydrogen phosphate, sodium acetate, potassium acetate, sodium lactate, tris(hydroxymethyl)amine, etc. The pH adjusters referred to here exclude the above-mentioned halide salts, ammonium salts, and basic compounds. Among the above examples, sodium dihydrogen phosphate, disodium hydrogen phosphate, potassium dihydrogen phosphate, disodium hydrogen phosphate, etc., which are not halogenated by reaction, are generally used.

[0036] The components contained in the solution are, for example, 1 The structure can be analyzed by H-NMR, and the yield of the target substance in the reaction can also be evaluated by the same method.

[0037] The pH of the solution at 25°C is not particularly limited, but from the viewpoint of improving the reaction efficiency, it is usually 6 or higher, preferably 7 or higher, more preferably 7.5 or higher, and even more preferably 8 or higher, and although there is no particular need to set an upper limit for the pH, it is usually 14 or lower. The pH can be adjusted by the type and amount of a halide salt, ammonium salt, basic compound, pH adjuster, etc. The pH of a solution at 25°C can be measured using a general pH measuring device with a glass electrode.

[0038] <Other processes> The method for producing a halocarbonyl compound according to this embodiment may include steps other than the reaction steps described above, and an example is shown below.

[0039] (Cyclic compound synthesis process) In the method for producing a halocarbonyl compound according to this embodiment, a step of synthesizing a cyclic compound may be provided before the above-described reaction step. The method for synthesizing the cyclic compound is not particularly limited and can be performed by a known method, for example, by the method shown in the above-described method for producing a cyclic compound.

[0040] (Solution preparation process) The method for producing a halocarbonyl compound according to this embodiment may include a solution preparation step of preparing a solution prior to the reaction step. The method for preparing the solution is not particularly limited, and examples thereof include a method in which raw materials other than the solvent that can be used as described above are weighed, added to a solvent, and dissolved under stirring to obtain a solution.

[0041] Furthermore, when the halocarbonyl compound obtained by the above reaction step is used as a derivative, it may be subjected to further another reaction.

[0042] <Use of halocarbonyl compounds> The halocarbonyl compound obtained by the above-mentioned production method can be used in various fields, and its use is not limited, and it may be used as the compound itself, or may be used as a derivative to produce other compounds. For example, when the halocarbonyl compound is produced as a haloketone compound, it can be used as a building block for various pharmaceuticals and pharmaceutical candidate compounds, etc. [Example]

[0043] Next, specific embodiments of the present invention will be described in more detail with reference to examples, but the present invention is not limited to these examples.

[0044] <Raw materials> In this example, the raw materials listed in Table 1 below were used.

[0045] [Table 1]

[0046] <Yield> In the following Examples 2, 3, 6 to 9 and Comparative Example 1, the yield of the product was measured according to the following method. The product was dried under reduced pressure and the crude product was treated with N,N-dimethylacetamide (ultra Add 30-40 mg of dehydrated water (Wako Pure Chemical Industries), dissolve it completely in chloroform-d, Using NMR (VARIAN Gemini-300 spectrometer manufactured by Gemini Trust Company), 1 H-NMR was measured with a relaxation time of 10 seconds and an accumulation count of 16. The yield was determined from the integral ratio of the area of ​​the NMR peak at 2.94 ppm (N,N-dimethylacetamide, N-CH3, singlet) in the obtained spectrum to the NMR peak characteristic of the product (for example, 3.43 ppm (triplet) when the target product contains Br-CH2-CH2- in its partial structure). In the following Examples 1, 4, 5, and 10 to 12, the yield was determined as the isolation yield when the compound was actually isolated.

[0047] <Experiment 1: Substrate type> [Substrate: 1-phenylcyclohexanol] Example 1 6-Bromo-1-phenylhexan-1-one was synthesized from 1-phenylcyclohexanol by the following reaction.

[0048] [ka]

[0049] The reactor used was a cylindrical membraneless cell with a radius of 1 cm, a height of 10 cm, and a side tube. The electrodes used were a platinum anode electrode with a width of 1.0 cm and a height of 2.0 cm, and a zinc cathode electrode with a width of 1.0 cm and a height of 5.0 cm, both with platinum lead wires attached. A reaction vessel was charged with 1-phenylcyclohexanol (1.0 mmol, 176.3 mg), Magnesium bromide hexahydrate (1.0 mmol, 292.2 mg) was weighed out as a halogenide salt, and dissolved in methyl acetate (1.0 mL) and water (5.0 mL). A 25% aqueous solution of tetramethylammonium hydroxide (0.5 mmol, 180 μL) was added as an ammonium salt at room temperature under an air atmosphere, after which an electrode was immersed and the reaction vessel was sealed with a rubber stopper. A constant current of 50 mA was applied, with a charge of 289.5 coulombs, equivalent to 3 F / mol, while the mixture was vigorously stirred in an ice bath using a magnetic stirrer. A DC power supply was used for the application of the current. A generator (GP050-2, manufactured by Takasago Machinery Co., Ltd.) was used, and the amount of current applied was measured with a coulomb ampere meter (HF-201, manufactured by Hokuto Denko Corporation). The time required for application of current was 96 minutes. After application of current, saturated aqueous sodium thiosulfate solution (3.0 mL) was added, and the mixture was extracted three times with 10 mL of ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The mixture was then purified by silica gel column chromatography to obtain 6-bromo-1-phenylhexan-1-one (236.5 mg, 0.93 mmol). The yield of 6-bromo-1-phenylhexan-1-one was 93%. 1 The results of structural analysis using H-NMR are shown below. 1 H-NMR(400MHz,CHLOROFORM-D)δ7.97-7.95(m,2H),7.58-7.54(m,1H),7.48-7.44(m,2H),3.43(t,J=6.7Hz,2H),3.00(t,J=7.3Hz,2H),1.96-1 .89(m,2H),1.82-1.74(m,2H),1.58-1.50(m,2H) In Non-Patent Document 1, which describes the prior art, the reaction is carried out using 5 times the molar amount of magnesium chloride as a halogen cation source relative to the hydroxyl group-containing cyclic compound, whereas the production method of the present invention uses an equimolar amount of magnesium bromide as a halogen cation source, achieving a high yield. Furthermore, it has been shown that the reaction can be carried out without using oxidizing agents or heavy metals that are of concern for their impact on the human body and the environment.

[0050] Example 2 The experiment was carried out under the same conditions and procedures as in Example 1, except that magnesium bromide hexahydrate was replaced with tetramethylammonium bromide (1.0 mmol, 154 mg), to obtain 6-bromo-1-phenylhexan-1-one (171 mg, 0.67 mmol). The yield of 6-bromo-1-phenylhexan-1-one was 67%.

[0051] Example 3 The following procedure was carried out using the same electrode reaction vessel as in Example 1. 1-phenylcyclohexanol (1.0 mmol, 176.3 mg) and 1-phenylcyclohexanol (1.0 mmol, 176.3 mg) were added to the reaction vessel. Tetramethylammonium tetrafluoroborate (1.0 mmol, 154 mg) was weighed out and dissolved in methyl acetate (1.0 mL) and water (5.0 mL). Magnesium hydroxide (0.25 mmol, 15 mg) as a basic substance and tetramethylammonium tetrafluoroborate (0.2 mmol, 40 mg) as an ammonium salt were added at room temperature under an air atmosphere, and then electrodes were immersed in the reaction vessel, which was then capped with a rubber stopper. The reaction vessel was stirred vigorously in an ice bath using a magnetic stirrer at a constant current of 50 mA, with a charge equivalent to 3 F / mol. A current of 289.5 coulombs was applied. A DC power generator (GP050-2, manufactured by Takasago Machinery Co., Ltd.) was used for the current application, and the current was measured using a coulomb ampere meter (HF-201, manufactured by Hokuto Denko Corporation). The time required for the current application was 96 minutes. The current application was performed under illumination with a 25 W fluorescent lamp. After the current application, saturated aqueous sodium thiosulfate solution (3.0 mL) was added, and the mixture was extracted three times with 10 mL of ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The mixture was then purified by silica gel column chromatography to obtain 6-bromo-1-phenylhexan-1-one (219.3 mg, 0.86 mmol). The yield of 6-bromo-1-phenylhexan-1-one was 86%.

[0052] [Substrate: 1-phenylcyclopentanol] Example 4 First, the substrate, 1-phenylcyclopentanol, was synthesized as follows. In a flame-dried 100 mL round-bottom flask, cyclopentanone (5 mmol, 420.6 mg) was dissolved in 20 mL of tetrahydrofuran. A 1.0 mol / L phenylmagnesium bromide solution in tetrahydrofuran (1.5 equivalents, 7.5 mL) was added dropwise at -78°C under an argon atmosphere. After stirring at room temperature for 10 hours, saturated aqueous ammonium chloride solution (10 mL) was added in an ice bath, and the mixture was extracted three times with ethyl acetate (20 mL). The organic layer was dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The mixture was then purified by silica gel column chromatography to yield 1-phenylcyclopentanol (686.2 mg, 4.23 mmol).

[0053] Next, 5-bromo-1-phenylpentan-1-one was synthesized from 1-phenylcyclopentanol by the following reaction.

[0054] [ka]

[0055] The experiment was carried out under the same conditions and procedures as in Example 1, except that 1-phenylcyclopentanol (162.2 mg, 1.0 mmol) was used as the substrate and the current was applied for approximately 192 minutes (579 coulombs, equivalent to 6 F / mol) until the reaction was completed, to obtain 5-bromo-1-phenylpentan-1-one (198.5 mg, 0.82 mmol). The yield of 1-phenylpentan-1-one was 82%. 1 The results of structural analysis using H-NMR are shown below. 1 H-NMR(400MHz,CHLOROFORM-D)δ7.97-7.95(m ,2H),7.59-7.55(m,1H),7.49-7.45(m,2H),3.46(t,J=6.5Hz,2H),3.02(t,J=6.9Hz,2H),2.01-1.87(m,4H)

[0056] [Substrate: 1-(4-t-butylphenyl)cyclohexanol] Example 5 First, the substrate, 1-(4-t-butylphenyl)cyclohexanol, was synthesized as follows. Magnesium (364.6 mg, 15 mmol) and iodine (1000 mg) were placed in a flame-dried 100 mL two-necked flask, and diethyl ether (10 mL) was added. The mixture was stirred at room temperature under an argon atmosphere for 30 minutes. Next, a solution of 1-bromo-4-t-butylbenzene (3196.8 mg, 15 mmol) in diethyl ether (10 mL) was added dropwise, and the mixture was stirred at 35 °C for 2 hours. Then, a solution of cyclohexanone (490.7 mg, 5.0 mmol) in diethyl ether (10 mL) was added dropwise while cooling in an ice bath, and the mixture was stirred at room temperature for 10 hours. Saturated aqueous ammonium chloride (10 mL) was added in an ice bath, and the mixture was extracted three times with ethyl acetate (20 mL). The organic layer was dried over anhydrous sodium sulfate, the solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography to obtain 1-(4-t-butylphenyl)cyclohexanol (1092.1 mg, 4.7 mmol, yield 94%).

[0057] Next, 6-bromo-1-(4-t-butylphenyl)hexan-1-one was synthesized from 1-(4-t-butylphenyl)cyclohexanol by the following reaction.

[0058] [ka]

[0059] The experiment was carried out under the same conditions and procedures as in Example 1, except that 1-(4-t-butylphenyl)cyclohexanol (232.3 mg, 1 mmol) was used as the substrate and the amount of methyl acetate was changed from 1.0 mL to 2.0 mL, to obtain 6-bromo-1-(4-t-butylphenyl)hexan-1-one (280.1 mg, 0.90 mmol). The yield of 4-bromo-1-(4-t-butylphenyl)hexan-1-one was 90%. 1 The results of structural analysis using H-NMR are shown below. 1 H-NMR(400MHz,CHLOROFORM-D)δ7.89(dt,J=8 .6,1.9Hz,2H),7.46(dt,J=8.8,2.0Hz,2H),3.42(t,J=6.7Hz,2H),2.96(t, J=7.3Hz,2H),1.94-1.87(m,2H),1.56-1.48(m,2H),1.33(s,9H)

[0060] <Experiment 2: Types of electrodes> (Examples 6 and 7) The experiment was carried out under the same conditions and operations as in Example 1, except that the anode and cathode electrodes were used in the combinations shown in Table 2. The yield of the obtained 6-bromo-1-phenylhexan-1-one is also shown in Table 2.

[0061] [Table 2]

[0062] <Experiment 3: Types of Solvents> (Examples 8 and 9) The organic solvents shown in Table 3 were used instead of methyl acetate as the organic solvent, and the experiment was carried out under the same conditions and with the same procedures as in Example 1. The yield of the obtained 6-bromo-1-phenylhexan-1-one is also shown in Table 3.

[0063] [Table 3]

[0064] <Experiment 4: Substrate type, current amount, and solvent amount> Example 10 First, the substrate, 1-(4-t-butylphenyl)cyclohexanol, was synthesized as follows. In a flame-dried 100 mL round-bottom flask, 4-t-butylcyclohexanone (5 mmol, 771.3 mg) was dissolved in 20 mL of tetrahydrofuran. A 1.0 mol / L phenylmagnesium bromide solution in tetrahydrofuran (1.5 equivalents, 7.5 mL) was added dropwise at -78°C under an argon atmosphere. After stirring at room temperature for 10 hours, saturated aqueous ammonium chloride solution (10 mL) was added in an ice bath, and the mixture was extracted three times with ethyl acetate (20 mL). The organic layer was dried over anhydrous sodium sulfate, the solvent was evaporated under reduced pressure, and the mixture was purified by silica gel column chromatography to obtain 4-t-butyl-1-phenylcyclohexanol (260.9 mg, 1.1 mmol, 22% yield).

[0065] Next, 4-(2-bromoethyl)-5,5-dimethyl-1-phenylhexan-1-one was synthesized from 4-t-butyl-1-phenylcyclohexanol by the following reaction.

[0066] [ka]

[0067] The experiment was carried out under the same conditions and procedures as in Example 1, except that 232.4 mg (1.0 mmol) of 4-t-butyl-1-phenylcyclohexanol was used as the substrate, and the current was applied for approximately 192 minutes (579 coulombs, equivalent to 6 F / mol) until the reaction was complete, and 3.0 mL of methyl acetate was used as the solvent. 4-(2-bromoethyl)-5,5-dimethyl-1-phenylhexan-1-one (280.1 mg, 0.90 mmol) was obtained. The yield of 2-bromoethyl)-5,5-dimethyl-1-phenylhexan-1-one was 90%. 1 The results of structural analysis using H-NMR are shown below. 1 H-NMR(400MHz,CHLOROFORM-D)δ7.96-7.94(m ,2H),7.58-7.54(m,1H),7.48-7.44(m,2H),3.52-3.41(m,2H),3.13-2.96(m,2H),2.13-2.05(m,1H) ,2.01-1.93(m,1H),1.67(td,J=14.5,6.5Hz,1H),1.50-1.41(m,1H),1.22-1.16(m,1H),0.91(s,9H)

[0068] <Experiment 5: Substrate type and current amount> Example 11 The substrate, 1-(4-chlorophenyl)cyclohexanol, was obtained as follows. A flame-dried 100 mL two-necked flask was charged with magnesium (972.2 mg, 4 Add diethyl ether (10 mL) and iodine (1 grain), and let it cool at room temperature. The mixture was stirred for 30 minutes under an argon atmosphere. Next, the prepared solution of 1-chloro-4-iodobenzene (4769.0 mg, 20 mmol) in diethyl ether (10 mL) was added dropwise to the mixture, and the mixture was stirred at 50°C for 2 hours. After that, the prepared solution of cyclohexanone (490.7 mg, 5.0 mmol) in diethyl ether (10 mL) was added dropwise while cooling in an ice bath. The mixture was stirred at room temperature for 1 hour and then at 55°C for 2 hours. The temperature was returned to room temperature and stirred for an additional 10 hours. Saturated aqueous ammonium chloride solution (10 mL) was added in an ice bath, and the mixture was extracted three times with ethyl acetate (20 mL). The organic layer was dried over anhydrous sodium sulfate, the solvent was evaporated under reduced pressure, and the mixture was purified by silica gel column chromatography to obtain 1-(4-chlorophenyl)cyclohexanol (806.2 mg, 3.8 mmol, yield 77%).

[0069] [ka]

[0070] Next, the same procedure as in Example 1 was carried out using 1-(4-chlorophenyl)cyclohexanol (210.7 mg, 1 mmol), except that current was applied for approximately 128 minutes (386 coulombs equivalent to 4 F / mol) until the reaction was completed, to obtain 6-bromo-1-(4-chlorophenyl)hexan-1-one (229.1 mg, 0.79 mmol, yield 79%). 1 H The results of structural analysis using -NMR are shown below. 1 H-NMR(400MHz,CHLOROFORM-D)δ7.89-7.86(m ,2H),7.43-7.40(m,2H),3.41(t,J=6.7Hz,2H),2.95(t,J=7.2Hz,2H),1.93-1.86(m,2H),1.78-1.71(m,2H),1.55-1.47(m,2H),

[0071] Example 12 6-Bromo-1-methylhexan-1-one was synthesized from 1-methylcyclohexanol by the following reaction.

[0072] [ka]

[0073] The same procedure as in Example 1 was carried out, except that 1-methylcyclohexanol (114.19 mg, 1.0 mmol) was used as the substrate and the current was applied for approximately 128 minutes (386 coulombs equivalent to 4 F / mol) until the reaction was completed, to obtain 7-bromoheptan-2-one (136.5 mg, 0.71 mmol, 71% yield). 1 Structural analysis using H-NMR is shown below. 1 H-NMR(400MHz,CHLOROFORM-D)δ3.41(t,J=6. 7Hz,2H),2.15(s,3H),1.92-1.82(m,2H),1.65-1.55(m,2H),1.49-1.38(m,2H),

[0074] (Comparative Example 1) The experiment was carried out under the same conditions and procedures as in Example 2, except that ammonium salt (25% aqueous tetramethylammonium hydroxide solution) was not used, to obtain 6-bromo-1-phenylhexan-1-one (89.3 mg, 0.35 mmol). The yield of 6-bromo-1-phenylhexan-1-one was 35%. In comparison with Example 2 above, when no ammonium salt was used, the yield was significantly reduced. I found out that.

[0075] As described above, according to the present invention, it is possible to provide a method for producing a halocarbonyl compound in a high yield while reducing the amount of a halogen cation source used and without requiring an expensive oxidizing agent or a metal salt that may remain.

Claims

1. The method includes a reaction step of electrolytically reacting a cyclic compound having a structure represented by the following formula (A-1) or (A-8) in a solution containing a halide salt and an ammonium salt to obtain a halocarbonyl compound represented by the following formula (1'): the solution contains a basic compound; The content of heavy metals in the solution is 1×10 －６ mol / L or less. 【Chemical 1】 (The cyclic compound is a compound in which the carbon atoms constituting the ring have hydrogen or a monovalent substituent (provided that R １ and the divalent hydrocarbon group of the ring are not bonded to each other; １ represents hydrogen or a monovalent organic group; the monovalent organic group is an optionally substituted alkyl group having 1 to 20 carbon atoms, an optionally substituted alkenyl group having 1 to 20 carbon atoms, an optionally substituted alkynyl group having 1 to 20 carbon atoms, an optionally substituted alkoxy group having 1 to 20 carbon atoms, -C≡N, -NR a R b R c , -C(═O)OH, -C(═O)OR′, -C(═O)R′, -SH, -SiR a R b R c , -BH 2 , -SeH, an optionally substituted monovalent aliphatic hydrocarbon ring group, an optionally substituted monovalent aromatic hydrocarbon ring group, or an optionally substituted monovalent aromatic heterocyclic group; R′, R a , R b , and R c independently represent hydrogen or an optionally substituted alkyl group having 1 to 20 carbon atoms; R ２ teeth, represents an alkylene group having 4 to 5 carbon atoms which may have a substituent, and the halocarbonyl compound represented by the formula (1') is a product corresponding to the cyclic compound; and Z represents a halogen group.

2. 2. The method for producing a halocarbonyl compound according to claim 1, wherein in the cyclic compound, the monovalent organic group that may be substituted on the carbon atom constituting the ring is an alkyl group having 1 to 12 carbon atoms.

3. The method for producing a halocarbonyl compound according to claim 1 or 2, wherein the solution contains at least an organic solvent or water.

4. The method for producing a halocarbonyl compound according to claim 3 , wherein the solution comprises an organic solvent and water.

5. The method for producing a halocarbonyl compound according to any one of claims 1 to 4, wherein the halide salt is magnesium bromide, magnesium chloride, or magnesium iodide.

6. The method for producing a halocarbonyl compound according to any one of claims 1 to 5, wherein the basic compound is a hydroxide or a carbonate.

7. The method for producing a halocarbonyl compound according to any one of claims 1 to 6, wherein the reaction step is carried out by irradiating light to carry out an electrolytic reaction.

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