JP7743010B2 - Method for producing halocarbonyl compounds - Google Patents

Description

The present invention relates to a method for producing a halocarbonyl compound.

Halocarbonyl compounds are used in a wide range of fields for various applications. 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 such method utilizes the regioselective oxidative cleavage reaction of hydroxyl-containing cyclic compounds such as cycloalkanols having a C(sp ³ )-C(sp ³ ) 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 carrying out a cleavage reaction of a hydroxyl-containing cyclic compound by reacting the hydroxyl-containing cyclic compound with a compound having an N-SCF bond.

Benjamin D. W. Allen, et al., Organic Letters, 2019, 21, 92141-9246 Tengfei Ji, et al., Organic Letters, 2020, 22, 2579-2583

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.

As a result of extensive research into resolving the above-mentioned issues, the inventors discovered that the above-mentioned issues could be resolved by using a specific substance, leading to the completion of the present invention.

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'):
(The cyclic compound represented by the above formula (1) is a compound having a ring A composed of a carbon having a hydroxy group and R ¹ and a divalent hydrocarbon group of 2 to 12 carbon atoms which may have a substituent bonded to the carbon, wherein a carbon constituting the hydrocarbon group may be substituted with nitrogen, oxygen, or sulfur, and wherein R ¹ and the divalent hydrocarbon group of 2 to 12 carbon atoms which may have a substituent may bond to form a ring; in the above formulas (1) and (1'), R ¹ represents hydrogen or a monovalent organic group; R ² represents a divalent hydrocarbon group of 2 to 12 carbon atoms which may have a substituent, wherein a carbon 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):
(In the above formulas (2) to (5) and (2') to (5'), R ¹ has the same meaning as R ¹ in the above formula (1); R ³ to R ⁸ independently represent hydrogen, a halogen group, or a monovalent organic group; X represents a single bond or a divalent hydrocarbon group of 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; W represents a trivalent hydrocarbon group of 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; Y represents a tetravalent hydrocarbon group of 2 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; Z has the same meaning as Z in the above formula (1'); in each formula, R ³ to R ⁸ , X, and Y may be bonded to each other to form a ring; and 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 formulas (2) to (5) has a structure represented by any one of formulas (A-1) to (A-9) below, and a carbon or nitrogen constituting a ring in the structure has hydrogen or a monovalent organic group as a substituent.
(In the above formulas (A-1) to (A-9), R ¹ independently has the same meaning as R ¹ in the above formula (1).)
[5] The method for producing a halocarbonyl compound according to [4], wherein in the compounds having structures represented by formulas (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 light in the reaction step.

The present invention provides a method for producing halocarbonyl compounds in high yields while reducing the amount of halogen cation source used and without the need for expensive oxidizing agents or metal salts that may remain.

The following describes in detail the embodiments of the present invention, but these descriptions are merely 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.

One embodiment of the method for producing a halocarbonyl compound (hereinafter also referred to simply as the "method for producing a halocarbonyl compound") is a method for producing a halocarbonyl compound, which includes a reaction step of electrolytically reacting a cyclic compound represented by the following formula (1) (hereinafter also referred to as the "substrate") 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 formula (1) above is a compound having a ring A composed of a carbon atom having a hydroxy group and ^R1 and a divalent hydrocarbon group of 2 to 12 carbon atoms, which may have a substituent, bonded to the carbon atom, and wherein a carbon atom constituting the hydrocarbon group may be substituted with nitrogen, oxygen, or sulfur, and wherein ^R1 and the divalent hydrocarbon group of 2 to 12 carbon atoms, which may have a substituent, may bond to form a ring; in the formulas (1) and (1'), ^R1 represents hydrogen or a monovalent organic group; ^R2 represents a divalent hydrocarbon group of 2 to 12 carbon atoms, which may have a substituent, and wherein 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.

In this specification, the monovalent organic group refers to 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, an optionally substituted monovalent aromatic heterocyclic group, and the like, and R′, R ^a , R ^b , and R ^c independently represent hydrogen or an optionally substituted alkyl group having 1 to 20 carbon atoms.
In addition, in this specification, the substituent in the expression "may have a substituent" means 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, -NH ₃ , -C(═O)OH, -C(═O)OR', -C(═O)R', -SH, -SiR ^a R ^b R ^c , -BH ₂ , -SeH, a monovalent aliphatic hydrocarbon ring group, a monovalent aromatic hydrocarbon ring group, a monovalent aromatic heterocyclic group, etc., and R', R ^a , R ^b , and R ^c independently represent hydrogen or an alkyl group having 1 to 20 carbon atoms.

<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').

The cyclic compound represented by formula (1) is a compound having a ring A composed of a carbon having a hydroxy group and ^R1 and a divalent hydrocarbon group of 2 to 12 carbon atoms which may have a substituent and is bonded to the carbon, wherein a carbon constituting the hydrocarbon group may be substituted with nitrogen, oxygen, or sulfur, and wherein ^R1 and the divalent hydrocarbon group of 2 to 12 carbon atoms which may have a substituent may bond to form a ring. In addition, an example of a compound having a ring A in which ^R1 and the divalent hydrocarbon group of 2 to 12 carbon atoms which may have a substituent are bonded to each other is 1-adamantanol.
R ¹ in formulas (1) and (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, and from the viewpoint of preventing a side reaction due to unintended bromination of R ¹ , preferably a straight-chain alkyl group such as a methyl group, an ethyl group, a propyl group, or an n-butyl group.
^R2 in formula (1') 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.

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 halide salts described below, Cl, Br, or I are preferred, and Br is particularly preferred.

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, due to its ease of availability and industrial usefulness. It is preferable that the halocarbonyl compounds obtained by electrolytically reacting the cyclic compound are compounds represented by formulas (2') to (5') below, respectively, for the compounds represented by formulas (2) to (5). Specifically, by electrolytically reacting the compounds represented by formulas (2) to (5) below 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.

In the above formulas (2) to (5) and (2') to (5'), R ¹ has the same meaning as R ¹ in the above formula (1), including preferred conditions.
In the above formulas (2) to (5) and (2′) to (5′), R ³ to R ⁸ independently represent 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 from the viewpoint of preventing a side reaction due to unintended bromination of R ³ to R ⁸ , preferably a straight-chain alkyl group 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 a carbon atom 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 a carbon atom 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 the preferred conditions.
In each formula, R ³ to 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.
The hydrocarbon groups in X, Y, and Z may be linear, branched, or have a cyclic structure.

At least one compound selected from the group of compounds represented by formulas (2) to (5) above preferably has a structure represented by formulas (A-1) to (A-9) below, 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.

In the above formulas (A-1) to (A-9), R ¹ has the same meaning as R ¹ in the above formula (1), including preferred conditions.
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 a side reaction of the organic group.

From the standpoint of ease 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.

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 ^R9 is a group selected from an alkyl group having 1 to 12 carbon atoms, a phenyl group, a trihalogenomethyl group, and a cyano group. However, the hydrogen atoms at positions 2 to 5 of the benzene ring of the phenyl group in ^R9 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. More specifically, for example, the compound may be one in which ^R9 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.

The method for producing the cyclic compound represented by formula (1) above is not particularly limited, and it can be produced using known methods, or commercially available products can also be used. Specific production methods include, for example, dissolving a cycloalkanone in a solvent such as tetrahydrofuran, adding an aryl metal halide compound, and then adding an aqueous ammonium chloride solution, extracting with ethyl acetate, and isolating and purifying the organic layer.

<Reaction step>
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.

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, and may be, for example, 0.1 cm ^{or more} and 10,000 ^cm or less in volume, or 0.5 ^cm or more and 1,000 cm or ^less . The material of the reaction vessel is also not particularly limited, and known materials can be used.
The type of electrode is not particularly limited, and for example, gold, platinum, graphite, or the like can be used for the anode (positive electrode), and gold, platinum, zinc, iron, nickel, molybdenum, copper, or the like can be used for the cathode (negative electrode). 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 appropriately selected depending on the reaction vessel used and the volume of the solvent to be reacted. For example, it may be 0.1 ^cm to 5,000 ^cm , or ¹ cm to 1,000 ^cm , or even ¹ cm to 200 ^cm .
The current flowing between the pair of electrodes is not particularly limited, and may be, for example, 0.1 mA/cm ² or more and 1,000 mA/cm ² or less, or 1 mA/cm ² or more and 500 mA/cm ² or less, in terms of current density per unit area.
The total amount of charge 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.

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, and the type and intensity of the light are not particularly limited. 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. The light intensity (radiant intensity, unit: Jm ^- 2s ^-1 ) may be, for example, 0.1 Jm ^- 2s ^-1 or more and 500 Jm ^- 2s ^-1 W or less, or 1 Jm ^- 2s ^-1 W or more and 100 Jm ^- 2s ^-1 W or less. For reference, the radiant intensity of a room illuminated by fluorescent light is 2.2 Jm ^- 2s ^-1 , and 440 Jm ^- 2s ^-1 under direct sunlight at midday.

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 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, even more preferably 5 mol/L or less, and particularly preferably 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.

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 reducing costs 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, and Pu. The content of heavy metals in the solution is preferably 1× ¹⁰ mol/L or less, more preferably 1× ¹⁰ mol/L or less, even more preferably 1× ¹⁰ mol/L or less, and preferably 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.

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 reaction efficiency, it is preferable to use a salt of tetraalkylammonium and a hydrophobic anion. Examples of the hydrophobic anion include organic acid ions such as acetate ion and lactate ion, and borate ions such as tetrafluoroborate and tetraphenylborate. However, from the viewpoint of the performance as a correlation migration catalyst when forming a salt with ammonium, organic acid ions and borate ions are generally used. Specific examples of the ammonium salt include 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.
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.

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, and even more preferably 0.2 or more, and also usually 0.5 or more, preferably 0.6 or more, more preferably 0.8 or more, and 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.

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 _PF6 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.
The water content in the solution is not particularly limited, but from the viewpoint of efficiently proceeding with the reaction, it is usually 1 vol% or more, preferably 5 vol% or more, more preferably 10 vol% or more, even more preferably 15 vol% or more, and particularly preferably 20 vol% or more, and is usually 99 vol% or less, preferably 97 vol% or less, more preferably 95 vol% or less, even more preferably 92 vol% or less, and particularly preferably 90 vol% or less.

The solution may contain components other than the above components (other 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.

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

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 more, preferably 7 or more, more preferably 7.5 or more, and even more preferably 8 or more, and the upper limit of the pH does not need to be particularly set, but is usually 14 or less. The pH can be adjusted by the type and amount of a halide salt, ammonium salt, basic compound, pH adjuster, etc.
The pH of the solution at 25° C. can be measured using a general pH measuring device with a glass electrode.

<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.

(Cyclic compound synthesis step)
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.

(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.

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

<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.

Specific embodiments of the present invention will now be described in more detail using examples, but the present invention is not limited to these examples.

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

<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 30-40 mg of N,N-dimethylacetamide (ultra-dehydrated, Wako Pure Chemical Industries) was added to the crude product, which was then completely dissolved in chloroform-d.
Using an 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-CH ₃ , 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-CH ₂ -CH ₂ - in its partial structure).
In the following Examples 1, 4, 5, and 10 to 12, the yield was determined as the isolation yield of the actual compound.

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

The reaction vessel 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 platinum lead wire attached thereto, and a zinc cathode electrode with a width of 1.0 cm and a height of 5.0 cm.
1-Phenylcyclohexanol (1.0 mmol, 176.3 mg) and magnesium bromide hexahydrate (1.0 mmol, 292.2 mg) as a halide salt were weighed into a reaction vessel, and methyl acetate (1.0 mL) and water (5.0 mL) were added and dissolved. At room temperature and under air, a 25% aqueous solution of tetramethylammonium hydroxide (0.5 mmol, 180 μL) as an ammonium salt was added, after which an electrode was immersed and the reaction vessel was sealed with a rubber stopper. While vigorously stirring using a magnetic stirrer in an ice bath, a constant current of 50 mA was applied, carrying 289.5 coulombs, equivalent to a charge of 3 F/mol. A DC power supply generator (GP050-2, manufactured by Takasago Machinery Co., Ltd.) was used for the application of electricity, and the amount of electricity applied was measured using a coulomb ampere meter (HF-201, manufactured by Hokuto Denko Corporation). The application time was 96 minutes. After applying 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, the solvent was evaporated under reduced pressure, and 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%. The results of structural analysis using ¹ 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 magnesium chloride as a halogen cation source in a molar amount five times that of the hydroxyl group-containing cyclic compound, whereas the production method of the present invention uses magnesium bromide as a halogen cation source in an equimolar amount, achieving a high yield. Furthermore, it has been shown that the reaction can be carried out without using an oxidizing agent or heavy metals that may have an adverse effect on the human body and the environment.

Example 2
An experiment was carried out under the same conditions and with the same procedure 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%.

Example 3
The following procedure was performed using the same electrode reaction vessel as in Example 1. 1-Phenylcyclohexanol (1.0 mmol, 176.3 mg) and tetramethylammonium bromide (1.0 mmol, 154 mg) as a halide salt were weighed into the reaction vessel, and methyl acetate (1.0 mL) and water (5.0 mL) were added to dissolve the contents. 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, after which the electrode was immersed and the reaction vessel was sealed with a rubber stopper. While vigorously stirring the mixture in an ice bath using a magnetic stirrer, a constant current of 50 mA was applied, with a charge of 289.5 coulombs, equivalent to 3 F/mol. A DC power supply generator (GP050-2, manufactured by Takasago Machinery Co., Ltd.) was used for the application of electricity, and the amount of current was measured using a coulomb ampere meter (HF-201, manufactured by Hokuto Denko Corporation). The time required for applying the current was 96 minutes. The current was applied under irradiation with light from a 25 W fluorescent lamp. After applying the current, a saturated aqueous solution of sodium thiosulfate (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 resulting mixture was 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%.

[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 tetrahydrofuran solution (1.5 equivalents, 7.5 mL) was added dropwise at -78°C under an argon stream. 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 obtain 1-phenylcyclopentanol (686.2 mg, 4.23 mmol).

Next, 5-bromo-1-phenylpentan-1-one was synthesized from 1-phenylcyclopentanol using the following reaction:

The experiment was carried out under the same conditions and with the same procedures as in Example 1, except that 1-phenylcyclopentanol (162.2 mg, 1.0 mmol) was used as the substrate and a current (579 coulombs equivalent to 6 F/mol) was applied for approximately 192 minutes 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%. The results of structural analysis using ¹ H-NMR are shown below.
^1H -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)

[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, the prepared 1-bromo-4-t-butylbenzene (3196.8 mg, 15 mmol) in diethyl ether (10 mL) solution was added dropwise, and the mixture was stirred at 35°C for 2 hours. Subsequently, the prepared cyclohexanone (490.7 mg, 5.0 mmol) in diethyl ether (10 mL) solution was added dropwise while cooling in an ice bath, and the mixture was stirred at room temperature for 10 hours. A 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 residue was purified by silica gel column chromatography to obtain 1-(4-t-butylphenyl)cyclohexanol (1092.1 mg, 4.7 mmol, yield 94%).

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

An 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 1-bromo-1-(4-t-butylphenyl)hexan-1-one was 90%. The results of structural analysis using ¹ H-NMR are shown below.
¹ H-NMR (400 MHz, 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)

<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.

<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 yields of the obtained 6-bromo-1-phenylhexan-1-one are also shown in Table 3.

<Experiment 4: Type of substrate, amount of current applied, amount of solvent>
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 stream. 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 obtain 4-t-butyl-1-phenylcyclohexanol (260.9 mg, 1.1 mmol, 22% yield).

Next, 4-(2-bromoethyl)-5,5-dimethyl-1-phenylhexan-1-one was synthesized from 4-t-butyl-1-phenylcyclohexanol using the following reaction:

The experiment was carried out under the same conditions and procedures as in Example 1, except that 4-t-butyl-1-phenylcyclohexanol (232.4 mg, 1.0 mmol) was used as the substrate, and current was applied for approximately 192 minutes (579 coulombs equivalent to 6 F/mol) until the reaction was completed, and 3.0 mL of methyl acetate was used as the solvent, to obtain 4-(2-bromoethyl)-5,5-dimethyl-1-phenylhexan-1-one (280.1 mg, 0.90 mmol).
The yield of 2-bromoethyl)-5,5-dimethyl-1-phenylhexan-1-one was 90%. The results of structural analysis using ¹ H-NMR are shown below.
^1H -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)

<Experiment 5: Substrate type and current amount>
Example 11
The substrate, 1-(4-chlorophenyl)cyclohexanol, was obtained as follows: In a flame-dried 100 mL two-necked flask, magnesium (972.2 mg, 4
100 mmol) and iodine (1 grain) were taken, and diethyl ether (10 mL) was added and the mixture was stirred at room temperature under an argon atmosphere for 30 minutes. Next, the prepared 1-chloro-4-iodobenzene (4769.0 mg, 20 mmol) in diethyl ether (10 mL) solution was added dropwise, and the mixture was stirred at 50°C for 2 hours. Then, while cooling in an ice bath, the prepared cyclohexanone (490.7 mg, 5.0 mmol) in diethyl ether (10 mL) solution was added dropwise, and the mixture was stirred at room temperature for 1 hour, and then at 55°C for 2 hours. The mixture 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, 77% yield).

Next, 1-(4-chlorophenyl)cyclohexanol (210.7 mg, 1 mmol) was used, and the same procedure as in Example 1 was carried out, 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%).
The results of structural analysis using -NMR are shown below.
^1H -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),

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

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 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, yield 71%). The results of structural analysis using ¹ H-NMR are shown below.
¹ H-NMR (400 MHz, 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),

(Comparative Example 1)
The experiment was carried out under the same conditions and procedures as in Example 2, except that an 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%.
Comparison with Example 2 above reveals that the yield is significantly reduced when no ammonium salt is used.

As described above, the present invention provides a method for producing halocarbonyl compounds in high yields while reducing the amount of halogen cation source used and without the need for expensive oxidizing agents or metal salts that may remain.

Claims (7)

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 method for producing a halocarbonyl compound, wherein the content of heavy metals in the solution is 1×10 ⁻⁶ mol/L or less.

(The cyclic compound is a compound in which a carbon atom constituting the ring has hydrogen or a monovalent substituent (provided that R ¹ is not bonded to the divalent hydrocarbon group of the ring); R ¹ represents hydrogen or a monovalent organic group ; the monovalent organic group is 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 , -BH ₂ , -SeH, a monovalent aliphatic hydrocarbon ring group which may have a substituent, a monovalent aromatic hydrocarbon ring group which may have a substituent, or a monovalent aromatic heterocyclic group which may have a substituent; and R′, R ^a , R ^b R ^c independently represents hydrogen or an alkyl group having 1 to 20 carbon atoms which may have a substituent ; R ² represents
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. 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 atoms constituting the ring is an alkyl group having 1 to 12 carbon atoms. The method for producing a halocarbonyl compound according to claim 1 or 2, wherein the solution contains at least an organic solvent or water. The method for producing a halocarbonyl compound according to claim 3, wherein the solution contains an organic solvent and water. 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. 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. The method for producing a halocarbonyl compound according to any one of claims 1 to 6, wherein the reaction step involves irradiating the compound with light to carry out an electrolytic reaction.