JP6191325B2 - Method for deuteration of aromatic compounds - Google Patents

Description

  The present invention relates to a method for deuterating an aromatic compound that does not require hydrogen gas or deuterium gas.

  Deuterated (deuterated and tritiated) compounds (deuterated compounds) are considered useful for various purposes. For example, deuterated compounds are very useful for elucidating the reaction mechanism and substance metabolism, and are widely used as labeling compounds. Further, the compounds have stability and properties of the compounds themselves due to their isotope effects. Since it changes, it is said that it is useful also as a pharmaceutical, an agrochemical, an organic electroluminescent material, etc. In addition, it is said to be useful as a labeling compound when investigating absorption, distribution, blood concentration, excretion, metabolism, etc. of pharmaceuticals etc. by animal experiments. Therefore, research using deuterated compounds has been actively conducted in these fields in recent years.

Conventionally, various methods have been used to obtain such a deuterated compound. Among them, deuteration of aromatic rings is difficult, and various studies have been made to obtain it efficiently and industrially. It was. However, in the conventional deuteration reaction of aromatic compounds, the metal catalyst to be used is activated with hydrogen gas or deuterium gas in advance and then deuteration reaction is performed, or deuterium is present in the presence of hydrogen gas or deuterium gas. It was necessary to carry out the reaction. For this reason, the reaction system is required to have hermeticity and the operation is complicated.
As a result of earnest research to solve the above problems, the present inventors have conducted a deuteration reaction of an aromatic compound using a platinum catalyst in the presence of 2-propanol, 2-butanol or 3-pentanol. The present inventors have found that the target compound hydrogen can be efficiently deuterated without previously activating the catalyst with hydrogen gas or deuterium gas and without allowing hydrogen gas or deuterium gas to coexist in the reaction system. The present invention has been completed.

  In the present invention, in the presence of at least one solution selected from 2-propanol, 2-butanol and 3-pentanol and a catalyst selected from a platinum catalyst, a rhodium catalyst and a ruthenium catalyst, deuterated water and a deuterated solvent are used. The present invention relates to a method for deuterating an aromatic compound, which comprises contacting a selected deuterium source with an aromatic compound.

According to the method of the present invention, since hydrogen gas or deuterium gas is not required, the reaction can proceed safely. In addition, since the reaction proceeds even if the temperature does not exceed 100 ° C., the reaction can proceed safely, and it is not necessary to use a pressure-resistant vessel such as an autoclave, and a simple operation is possible.
Furthermore, according to the method of the present invention, it becomes possible to efficiently deuterate hydrogen atoms in an aromatic compound, particularly hydrogen atoms in an aromatic ring. Even if it is an unsubstituted aromatic hydrocarbon, which has been considered difficult to be deuterated, an aromatic hydrocarbon having a fluorine atom as a substituent, or an aromatic heterocyclic ring containing a sulfur atom, the hydrogen atom is deuterated. can do. Moreover, even if the compound has a carbonyl group or a double bond, they are not reduced, and the effect that the hydrogen atom of the target compound can be deuterated is also achieved.

[Catalyst according to the present invention]
Examples of the catalyst according to the present invention include a platinum catalyst, a rhodium catalyst, and a ruthenium catalyst, and among them, a platinum catalyst exhibiting a high deuteration rate is preferable. The catalyst according to the present invention need not be activated in advance with hydrogen gas, deuterium gas, or the like, but may be activated.

  Examples of the platinum catalyst according to the present invention include those in which the valence of the platinum atom is usually 0 to 4, preferably 0 to 2, and more preferably 0. Specifically, for example, platinum metal, platinum compound, A platinum complex etc. are mentioned.

The platinum metal may be the metal itself, or may be one obtained by immobilizing platinum metal on a carrier such as carbon material such as activated carbon, alumina, silica, diatomaceous earth, molecular sieve, silk, or polymer. As the carrier, any carrier known per se used in this field can be used. Specifically, the platinum metal is preferably platinum carbon or platinum alumina, and more preferably platinum carbon.
Examples of the platinum compound include platinum oxide such as platinum dioxide and platinum chloride.
Platinum complexes include 1,5-cyclooctadiene (COD), dibenzylideneacetone (DBA), tricyclohexylphosphine (PCy ₃ ), triethoxyphosphine (P (OEt) ₃ ), tritert-butoxyphosphine (P ( O ^t Bu) ₃ ), bipyridine (BPY), phenanthroline (PHE), triphenylphosphine (PPh ₃ ), 1,2-bis (diphenylphosphino) ethane (DPPE), triphenoxyphosphine (P (OPh) ₃ ) And those having tri-o-tolylphosphine (P (o-tolyl) ₃ ) as a ligand, such as PtCl ₂ (COD), PtCl ₂ (DBA), PtCl ₂ (PCy ₃ ). ₂ , PtCl ₂ (P (OEt) ₃ ) ₂ , PtCl ₂ (P (O ^t Bu) ₃ ) ₂ , PtCl ₂ (BPY), PtCl ₂ (PHE), Pt (PPh ₃ ) ₄ , Pt (COD) ₂ , Pt (DBA) ₂ , Pt (BPY) ₂ , Pt (PHE) _{2 and the} like.

  Among the platinum catalysts, platinum metal and platinum compounds are preferable, among which platinum carbon, platinum alumina, and platinum oxide are preferable, and platinum carbon is more preferable.

  Examples of the rhodium catalyst according to the present invention include those in which the valence of the rhodium atom is usually 0 to 3, preferably 0. Specific examples include rhodium metal, rhodium compounds, and rhodium complexes.

The rhodium metal may be a metal itself or a rhodium metal immobilized on a carrier such as carbon material (carbon) such as activated carbon, alumina, silica, zeolite, molecular sieve, ion exchange resin, polymer, etc. Of these, those fixed to carbon or alumina are preferable, and those supported on carbon are more preferable. As the carrier, any carrier known per se used in this field can be used. Specific examples of the rhodium metal include rhodium carbon.
Examples of the rhodium compound include rhodium oxide, rhodium chloride, and rhodium acetate.
Examples of the rhodium complex include RhCl (PPh ₃ ) ₃ having triphenylphosphine as a ligand.

  Examples of the ruthenium catalyst according to the present invention include those in which the valence of the ruthenium atom is usually 0 to 8, preferably 0. Specific examples include a ruthenium metal, a ruthenium compound, and a ruthenium complex.

The ruthenium metal may be a metal itself, which is fixed on a carrier such as carbon material (carbon) such as activated carbon, alumina, silica, zeolite, molecular sieve, ion exchange resin, polymer, etc. Of these, those fixed to carbon or alumina are preferable, and those supported on carbon are more preferable. As the carrier, any carrier known per se used in this field can be used. Specific examples of the ruthenium metal include ruthenium carbon.
Examples of the ruthenium compound include ruthenium hydroxide, ruthenium dioxide, ruthenium tetroxide, ruthenium chloride, ruthenium acetate and the like.
Examples of the ruthenium complex include RuCl ₂ (PPh ₃ ) ₃ having triphenylphosphine as a ligand.

  The amount of the catalyst according to the present invention varies depending on the type of the catalyst, but is usually 0.1 to 20 mol%, preferably 1 to 10 mol%, more preferably 1 to 5 mol% based on the substrate.

  In the method of the present invention, in addition to the catalyst according to the present invention, a platinum group catalyst (hereinafter sometimes abbreviated as the platinum group catalyst according to the present invention) coexists as a mixed catalyst, that is, platinum, rhodium and ruthenium. The aromatic compound according to the present invention and the deuterium source according to the present invention may be brought into contact with each other as a mixed catalyst of a catalyst selected from the above and a platinum group catalyst other than the catalyst. When the platinum group catalyst is used, the deuteration rate can be further improved. Examples of the platinum group catalyst according to the present invention include a platinum catalyst, a palladium catalyst, a rhodium catalyst, a ruthenium catalyst, a nickel catalyst, and a cobalt catalyst. Any of these catalysts may be used as long as they are known per se. Among these platinum group catalysts, a palladium catalyst is preferable.

  Specific examples of the platinum catalyst, rhodium catalyst, and ruthenium catalyst as the platinum group catalyst according to the present invention are the same as those described for the catalyst according to the present invention, and preferred ones are also the same.

As said palladium catalyst, the valence of a palladium atom is 0-4 valence normally, Preferably it is 0-2 valence, More preferably, it is 0 valence.
Specific examples of the palladium catalyst include palladium hydroxide catalysts such as palladium metal, palladium carbon, and Pd (OH) ₂ , palladium oxide catalysts such as PdO, and halogenated compounds such as PdBr ₂ , PdCl ₂ , and PdI ₂ . Palladium acetate catalysts such as palladium acetate (Pd (OAc) ₂ ), palladium trifluoroacetate (Pd (OCOCF ₃ ) ₂ ), such as acetate bis (triphenylphosphine) palladium [Pd (OAc) ₂ (PPh _{3) 2], Pd (PPh} 3) 4, Pd 2 (dba) 3, Pd (NH 3) 2 Cl 2, Pd (CH 3 CN) 2 Cl 2, dichlorobis (benzonitrile) palladium [Pd _{(PhCN) 2} Cl ₂ ], Pd (PPh ₃ ) (CH ₃ CN) ₂ Cl ₂ palladium metal complex catalysts which are coordinated with a ligand, and the like. Among them, palladium-carbon is preferred.

As said nickel catalyst, the valence of a nickel atom is 0-2 normally, Preferably the valence of 0 is mentioned.
Specific examples of the nickel catalyst include nickel catalysts such as nickel catalysts such as NiCl ₂ and NiO, such as NiCl ₂ (PPh ₃ ) ₂ , Ni (PPh ₃ ) ₄ , Ni (P (OPh) ₃ ) ₄ , Ni (Cod) A nickel catalyst coordinated to a ligand such as _{2 is} exemplified.

As said cobalt catalyst, the valence of a cobalt atom is 0 or 1 valence normally, Preferably a valence is mentioned.
Specific examples of the cobalt metal catalyst include a cobalt metal complex catalyst coordinated to a ligand such as Co (C ₃ H ₅ ) {P (OCH ₃ ) ₃ } ₃ .

  The amount of the platinum group catalyst according to the present invention varies depending on the amount of the catalyst according to the present invention, but is usually 0.5 to 20 mol%, preferably 1 to 10 mol%, more preferably 1 to 5 mol based on 1 mol of the substrate. %.

[Solution according to the present invention]
The solution according to the present invention is at least one selected from 2-propanol, 2-butanol and 3-pentanol. These solutions may be deuterated 2-propanol, deuterated 2-butanol, or deuterated 3-pentanol. When these are used, they can also be used as a deuterium source.

  Since the solution according to the present invention is considered to contribute to the activation of the catalyst according to the present invention, the amount used may be an excess amount relative to the catalyst according to the present invention, for example, according to the present invention. The amount is usually 10 to 2000 mol, preferably 10 to 1000 mol, more preferably 10 to 200 mol, relative to 1 mol of the catalyst. However, since the solution according to the present invention can also be used as a solvent, when the organic solvent according to the present invention which is a cosolvent is not used, the amount used is usually 1 to 100 mL, preferably 1 with respect to 1 mmol of the substrate. -10 mL.

[Deuterium source according to the present invention]
Examples of the deuterium source according to the present invention include heavy water or a deuterated solvent, but heavy water is preferable.

Examples of the deuterated solvent include deuterated 2-propanol (2-propanol-d ₈ , 2-propanol-d ₁ ), deuterated 2-butanol (2-butanol-d ₁₀ , 2- butanol -d _1), deuterated 3- propanol (3-propanol -d _1), and the like.

  The amount of heavy water or deuterated solvent used may be an excess amount relative to the amount of light hydrogen in the substrate (the aromatic compound according to the present invention), for example, relative to the total moles of light hydrogen in the aromatic compound. Usually, it is 10 to 1000 times mol, preferably 10 to 100 times mol.

[Aromatic Compound According to the Present Invention]
The aromatic compound according to the present invention used as a substrate includes (i) a substituted or unsubstituted aromatic hydrocarbon compound, (ii) a substituted or unsubstituted aromatic heterocyclic compound, iii) A compound represented by the general formula [1] having a substituent or unsubstituted.

  Examples of the substituent of the aromatic hydrocarbon compound, the aromatic heterocyclic compound, or the compound represented by the general formula [1] include, for example, an alkyl group having 1 to 6 carbon atoms, an alkenyl group having 2 to 6 carbon atoms, and the number of carbon atoms 1-6 alkoxy groups, C6-C10 aryl groups, hydroxyl groups, amino groups, carboxyl groups, halogeno groups, C2-C7 alkoxycarbonyl groups, C2-C7 alkylcarbonyl groups, C7 -11 arylcarbonyl group, C8-13 arylalkenyl group, C7-13 aryloxyalkyl group, C8-14 arylcarbonyloxyalkyl group, C2-10 alkylaminocarbonyl group , Alkylcarbonylamino group having 2 to 10 carbon atoms, alkylcarbonylalkenyl group having 4 to 7 carbon atoms, alkylcarbonyl having 4 to 7 carbon atoms Alkyl group, C12-20 diarylsilanol group, C6-C10 arylsulfonyl group, C6-C10 arylsulfonyloxy group, C1-C6 alkylsulfonyl group, C1-C6 Examples thereof include an alkylsulfonyloxy group, an alkylphosphorylalkyl group having 2 to 12 carbon atoms, and a heterocyclic group.

(I) A substituted or unsubstituted aromatic hydrocarbon compound The aromatic hydrocarbon compound in the substituted or unsubstituted aromatic hydrocarbon compound according to the present invention includes many rings having 1 to 6 rings. Examples include ring aromatic compounds, and specific examples include benzene, naphthalene, anthracene, naphthacene, pyrene, benzopyrene, and the like. In the aromatic hydrocarbon compound having a substituent, naphthalene or benzene is preferable, and benzene is more preferable. In the unsubstituted aromatic hydrocarbon compound, naphthalene, anthracene, naphthacene, pyrene, benzopyrene and the like are preferable, and naphthalene, anthracene, naphthacene, pyrene and the like are more preferable.

  The alkyl group having 1 to 6 carbon atoms in the substituent of the aromatic hydrocarbon compound may be linear, branched or cyclic, and specifically includes, for example, methyl group, ethyl group, n-propyl group, isopropyl Group, n-butyl group, isobutyl group, sec-butyl group, tert-butyl group, n-pentyl group, isopentyl group, sec-pentyl group, tert-pentyl group, neopentyl group, n-hexyl group, isohexyl group, 3 -Methylpentyl group, 2-methylpentyl group, 1,2-dimethylbutyl group, cyclopropyl group, cyclopentyl group, cyclohexyl group and the like are mentioned. Among them, methyl group, ethyl group, n-propyl group, n-butyl group N-pentyl group, n-hexyl group and the like are preferable, and ethyl group, n-butyl group, n-hexyl group and the like are more preferable.

  The alkenyl group having 2 to 6 carbon atoms in the substituent of the aromatic hydrocarbon compound may be linear, branched, or cyclic, and carbon- in the chain of the above alkyl group having 2 or more carbon atoms. Specific examples include one containing at least one carbon double bond, specifically, for example, vinyl group, allyl group, 1-propenyl group, isopropenyl group, 3-butenyl group, 2-butenyl group, 1- Butenyl group, 1,3-butadienyl group, 4-pentenyl group, 3-pentenyl group, 2-pentenyl group, 1-pentenyl group, 1,3-pentadienyl group, 2,4-pentadienyl group, 1,1-dimethyl- 2-propenyl group, 1-ethyl-2-propenyl group, 1,2-dimethyl-1-propenyl group, 1-methyl-1-butenyl group, 5-hexenyl group, 4-hexenyl group, 2-hexenyl group 1-hexenyl group, 1-cyclopropenyl group, 2-cyclopentenyl group, 2,4-cyclopentadienyl group, 1-cyclohexenyl group, 2-cyclohexenyl group, 3-cyclohexenyl group, etc. , Vinyl group, allyl group, 1-propenyl group and the like are preferable.

  The alkoxy group having 1 to 6 carbon atoms in the substituent of the aromatic hydrocarbon compound may be linear, branched or cyclic, and specifically includes, for example, methoxy group, ethoxy group, propyloxy group, isopropyloxy Group, butoxy group, isobutyloxy group, sec-butyloxy group, tert-butyloxy group, pentyloxy group, neopentyloxy group, hexyloxy group, isohexyloxy group, tert-hexyloxy group, cyclohexyloxy group and the like. Of these, a methoxy group, an isopropyloxy group, and the like are preferable, and a methoxy group is more preferable.

  Specifically as a C6-C10 aryl group in the substituent of an aromatic hydrocarbon compound, a phenyl group, a naphthyl group, etc. are mentioned specifically, Among these, a phenyl group etc. are preferable.

  Examples of the halogeno group in the substituent of the aromatic hydrocarbon compound include a fluoro group, a chloro group, a bromo group, and an iodo group, and a fluoro group and the like are preferable.

  The alkoxycarbonyl group having 2 to 7 carbon atoms in the substituent of the aromatic hydrocarbon compound may be linear, branched or cyclic, and specifically includes, for example, methoxycarbonyl group, ethoxycarbonyl group, propyloxycarbonyl Group, isopropyloxycarbonyl group, butoxycarbonyl group, isobutyloxycarbonyl group, sec-butyloxycarbonyl group, tert-butyloxycarbonyl group, pentyloxycarbonyl group, neopentyloxycarbonyl group, hexyloxycarbonyl group, isohexyloxycarbonyl Group, tert-hexyloxycarbonyl group, cyclohexyloxycarbonyl group and the like, among which ethoxycarbonyl group, propyloxycarbonyl group and the like are preferable.

  The alkylcarbonyl group having 2 to 7 carbon atoms in the substituent of the aromatic hydrocarbon compound may be linear or branched, and specifically includes, for example, a methylcarbonyl group, an ethylcarbonyl group, and an n-propylcarbonyl group. , Isopropylcarbonyl group, n-butylcarbonyl group, isobutylcarbonyl group, sec-butylcarbonyl group, tert-butylcarbonyl group, n-pentylcarbonyl group, isopentylcarbonyl group, sec-pentylcarbonyl group, tert-pentylcarbonyl group, Neopentylcarbonyl group, n-hexylcarbonyl group, isohexylcarbonyl group, 3-methylpentylcarbonyl group, 2-methylpentylcarbonyl group, 1,2-dimethylbutylcarbonyl group, cyclopropylcarbonyl group, cyclopentylcarbonyl Group, cyclohexylcarbonyl group and the like, among which methylcarbonyl group, tert-butylcarbonyl group, n-butylcarbonyl group, n-propylcarbonyl group and the like are preferable.

  Specific examples of the arylcarbonyl group having 7 to 11 carbon atoms in the substituent of the aromatic hydrocarbon compound include a phenylcarbonyl group and a naphthylcarbonyl group, and a phenylcarbonyl group is preferable.

  Specific examples of the arylalkenyl group having 8 to 13 carbon atoms in the substituent of the aromatic hydrocarbon compound include, for example, a phenyl vinyl group, a phenyl allyl group, a phenyl-1-propenyl group, a phenyl isopropenyl group, a phenyl 3- Butenyl group, phenyl-2-butenyl group, phenyl-1-butenyl group, phenyl-1,3-butadienyl group, phenyl-4-pentenyl group, phenyl-3-pentenyl group, phenyl-2-pentenyl group, phenyl-1 -Pentenyl group, phenyl-1,3-pentadienyl group, phenyl-2,4-pentadienyl group, phenyl-1,1-dimethyl-2-propenyl group, phenyl-1-ethyl-2-propenyl group, phenyl-1, 2-dimethyl-1-propenyl group, phenyl-1-methyl-1-butenyl group, phenyl-5 Hexenyl group, phenyl-4-hexenyl group, phenyl-2-hexenyl group, phenyl-1-hexenyl group, phenyl-1-cyclopropenyl group, phenyl-2-cyclopentenyl group, phenyl-2,4-cyclopentadienyl Group, phenyl-1-cyclohexenyl group, phenyl-2-cyclohexenyl group, phenyl-3-cyclohexenyl group, naphthylvinyl group, naphthylallyl group, naphthyl-1-propenyl group, naphthylisopropenyl group, naphthyl-3-butenyl Group, naphthyl-2-butenyl group, naphthyl-1-butenyl group, naphthyl-1,3-butadienyl group, naphthyl-4-pentenyl group, naphthyl-3-pentenyl group, naphthyl-2-pentenyl group, naphthyl-1- Pentenyl group, naphthyl-1,3-pentadienyl group, naphthy -2,4-pentadienyl group, naphthyl-1,1-dimethyl-2-propenyl group, naphthyl-1-ethyl-2-propenyl group, naphthyl-1,2-dimethyl-1-propenyl group, naphthyl-1- Methyl-1-butenyl group, naphthyl-5-hexenyl group, naphthyl-4-hexenyl group, naphthyl-2-hexenyl group, naphthyl-1-hexenyl group, naphthyl-1-cyclopropenyl group, naphthyl-2-cyclopentenyl group Naphthyl-2,4-cyclopentadienyl group, naphthyl-1-cyclohexenyl group, naphthyl-2-cyclohexenyl group, naphthyl-3-cyclohexenyl group, etc., among which phenyl vinyl group, naphthyl vinyl group Etc. are preferable, and a phenyl vinyl group is more preferable.

  As the aryloxyalkyl group having 7 to 13 carbon atoms in the substituent of the aromatic hydrocarbon compound, a phenyloxymethyl group, a phenyloxyethyl group, a phenyloxy-n-propyl group, a phenyloxyisopropyl group, a naphthyloxymethyl group, A naphthyloxyethyl group, a naphthyloxy-n-propyl group, a naphthyloxyisopropyl group, etc. are mentioned, Among them, a phenyloxymethyl group, a naphthyloxymethyl group, etc. are preferable, and a phenyloxymethyl group is more preferable.

  As the arylcarbonyloxyalkyl group having 8 to 14 carbon atoms in the substituent of the aromatic hydrocarbon compound, a phenylcarbonyloxymethyl group, a phenylcarbonyloxyethyl group, a phenylcarbonyloxy-n-propyl group, a phenylcarbonyloxyisopropyl group, A naphthylcarbonyloxymethyl group, a naphthylcarbonyloxyethyl group, a naphthylcarbonyloxy-n-propyl group, a naphthylcarbonyloxyisopropyl group, and the like. Among them, a phenylcarbonyloxymethyl group, a naphthylcarbonyloxymethyl group, and the like are preferable. An oxymethyl group is more preferred.

  Examples of the alkylaminocarbonyl group having 2 to 10 carbon atoms in the substituent of the aromatic hydrocarbon compound include a methylaminocarbonyl group, an ethylaminocarbonyl group, an n-propylaminocarbonyl group, an isopropylaminocarbonyl group, a dimethylaminocarbonyl group, and diethylamino. Examples include a carbonyl group, a di-n-propylaminocarbonyl group, a diisopropylaminocarbonyl group, and an ethylmethylaminocarbonyl group. Among them, a methylaminocarbonyl group and a dimethylaminocarbonyl group are preferable, and a methylaminocarbonyl group is more preferable.

  Examples of the alkylcarbonylamino group having 2 to 10 carbon atoms in the substituent of the aromatic hydrocarbon compound include a methylcarbonylamino group, an ethylcarbonylamino group, an n-propylcarbonylamino group, an isopropylcarbonylamino group, a dimethylcarbonylamino group, diethyl Examples include a carbonylamino group, a di-n-propylcarbonylamino group, a diisopropylcarbonylamino group, an ethylmethylcarbonylamino group, and the like. Among them, a methylcarbonylamino group, a dimethylcarbonylamino group, and the like are preferable, and a methylcarbonylamino group is more preferable. .

  Examples of the alkylcarbonylalkenyl group having 4 to 7 carbon atoms in the substituent of the aromatic hydrocarbon compound include a methylcarbonylvinyl group, a methylcarbonylallyl group, a methylcarbonyl-1-propenyl group, a methylcarbonylisopropenyl group, and an ethylcarbonylvinyl group. , Ethylcarbonylallyl group, ethylcarbonyl-1-propenyl group, ethylcarbonylisopropenyl group, n-propylcarbonylvinyl group, n-propylcarbonylallyl group, n-propylcarbonyl-1-propenyl group, n-propylcarbonylisopropenyl A methylcarbonylvinyl group, an ethylcarbonylvinyl group, and the like are preferable.

  Examples of the alkylcarbonylalkyl group having 4 to 7 carbon atoms in the substituent of the aromatic hydrocarbon compound include a methylcarbonylmethyl group, a methylcarbonylethyl group, a methylcarbonyl-n-propyl group, an ethylcarbonylmethyl group, an ethylcarbonylethyl group, Examples include an ethylcarbonyl-n-propyl group, an n-propylcarbonylmethyl group, an n-propylcarbonylethyl group, an n-propylcarbonyl-n-propyl group, and a methylcarbonylmethyl group and a methylcarbonylethyl group are preferable.

  Examples of the diarylsilanol group having 12 to 20 carbon atoms in the substituent of the aromatic hydrocarbon compound include a diphenylsilanol group, a dianthracenylphenylsilanol group, and an anthracenylphenylsilanol group, and a diphenylsilanol group is preferable.

  Examples of the arylsulfonyl group having 6 to 10 carbon atoms in the substituent of the aromatic hydrocarbon compound include a phenylsulfonyl group and an anthracenylsulfonyl group, and a phenylsulfonyl group is preferable.

  Examples of the arylsulfonyloxy group having 6 to 10 carbon atoms in the substituent of the aromatic hydrocarbon compound include a phenylsulfonyloxy group and an anthracenylsulfonyloxy group, and a phenylsulfonyloxy group is preferable.

  Examples of the alkylsulfonyl group having 1 to 6 carbon atoms in the substituent of the aromatic hydrocarbon compound include methylsulfonyl group, ethylsulfonyl group, n-propylsulfonyl group, n-butylsulfonyl group, tert-butylsulfonyl group, and n-pentyl. A sulfonyl group, n-hexylsulfonyl group, etc. are mentioned, A methylsulfonyl group is preferable.

  Examples of the alkylsulfonyloxy group having 1 to 6 carbon atoms in the substituent of the aromatic hydrocarbon compound include methylsulfonyloxy group, ethylsulfonyloxy group, n-propylsulfonyloxy group, n-butylsulfonyloxy group, tert-butylsulfonyl Examples include an oxy group, an n-pentylsulfonyloxy group, and an n-hexylsulfonyloxy group, and a methylsulfonyloxy group is preferable.

  Examples of the alkylphosphorylalkyl group having 2 to 12 carbon atoms in the substituent of the aromatic hydrocarbon compound include a methylphosphorylmethyl group, a dimethylphosphorylmethyl group, a diethylphosphorylmethyl group, a di-n-propylphosphorylmethyl group, and a diisopropylphosphorylmethyl group. Dimethylphosphorylethyl group, diethylphosphorylethyl group, di-n-propylphosphorylethyl group, diisopropylphosphorylethyl group, dimethylphosphoryl-n-propyl group, diethylphosphoryl-n-propyl group, di-n-propylphosphoryl-n- A propyl group, a diisopropyl phosphoryl-n-propyl group, etc. are mentioned, A dimethyl phosphoryl methyl group, a diethyl phosphoryl methyl group, etc. are preferable.

  As the heterocyclic group in the substituent of the aromatic hydrocarbon compound, a group derived from piperidine, a group derived from pyrrolidine, a group derived from pyrrole, a group derived from furan, a group derived from thiophene, a group derived from imidazole, a group derived from pyrazole, Examples include oxazole-derived groups, isoxazole-derived groups, thiazole-derived groups, isothiazole-derived groups, pyridine-derived groups, and the like. Among them, furan-derived groups, pyridine-derived groups, and the like are preferable.

  Among the above substituents, an alkyl group having 1 to 6 carbon atoms, an alkoxy group having 1 to 6 carbon atoms, an aryl group having 6 to 10 carbon atoms, a hydroxyl group, a carboxyl group, a halogeno group, and an alkoxycarbonyl group having 2 to 7 carbon atoms. , An alkylcarbonyl group having 2 to 7 carbon atoms, an arylcarbonyl group having 7 to 11 carbon atoms, an arylalkenyl group having 8 to 13 carbon atoms, an aryloxyalkyl group having 7 to 13 carbon atoms, and an arylcarbonyl group having 8 to 14 carbon atoms Oxyalkyl group, C2-C10 alkylaminocarbonyl group, C4-C7 alkylcarbonylalkyl, C2-C10 alkylcarbonylamino group, C12-C20 diarylsilanol group, C1-C1 6 alkylsulfonyloxy groups and the like, preferably an alkyl group having 1 to 6 carbon atoms, an aryl group having 6 to 10 carbon atoms, and a hydroxy acid A carboxyl group, an alkylcarbonyl group having 2 to 7 carbon atoms, an arylcarbonyl group having 7 to 11 carbon atoms, an arylalkenyl group having 8 to 13 carbon atoms, an alkylaminocarbonyl group having 2 to 10 carbon atoms, and 4 to 7 carbon atoms. Of these, alkylcarbonylalkyl is more preferred.

  The aromatic hydrocarbon compound having a substituent according to the present invention has at least one of the above-mentioned substituents, specifically, usually 1 to 3, preferably 1 to 2, more preferably 1. . Preferred examples thereof include, for example, methyl group, ethyl group, n-propyl group, n-butyl group, n-pentyl group, n-hexyl group, phenyl group, hydroxyl group, carboxyl group, fluoro group, chloro group, methoxycarbonyl. Group, ethoxycarbonyl group, n-propoxycarbonyl group, methylcarbonyl group, ethylcarbonyl group, n-propylcarbonyl group tert-butylcarbonyl group, n-butylcarbonyl group, phenylcarbonyl group, phenylvinyl group, naphthylvinyl group, phenoxy Methyl group, phenoxyethyl group, phenylcarbonyloxymethyl group, phenylcarbonyloxyethyl group, methylaminocarbonyl group, ethylaminocarbonyl group, methylcarbonylamino group, diphenylsilanol group, methylsulfonyloxy group, ethyls Usually one to three selected from Honiruokishi groups, preferably 1 to 2, more preferably benzene having one substituent.

(Ii) An aromatic heterocyclic compound having a substituent or an unsubstituted aromatic heterocyclic compound and an aromatic heterocyclic compound having a substituent and an unsubstituted aromatic heterocyclic compound include, for example, pyrrole, imidazole, Pyrazole, furan, thiophene, oxazole, isoxazole, thiazole, isothiazole, pyridine, pyrimidine, pyridazine, pyrazine, indole; benzothiazole, benzothiophene, benzimidazole, benzofuran, quinoline, isoquinoline, quinoxaline, chromene, isochromene, coumarin, chromone Phenothiazine, phenoxazine, carbazole, dibenzothiophene, etc., among which furan, indole, carbazole, benzothiophene, benzofuran, coumarin, dibenzothiophene, etc. Masui.

  Examples of the substituent of the aromatic heterocyclic compound having a substituent include the same substituents as those of the aromatic hydrocarbon compound. Among these, an alkyl group having 1 to 6 carbon atoms and an amino group are particularly preferable.

  The aromatic heterocyclic compound having a substituent usually has 1 to 3, preferably 1 to 2, and more preferably 1 substituent. Preferred examples thereof include, for example, ethyl group, n-butyl group, n-hexyl group, phenyl group, hydroxyl group, carboxyl group, methylcarbonyl group, tert-butylcarbonyl group, n-butylcarbonyl group, n-propylcarbonyl group. A furan, an indole, a carbazole having usually 1 to 3, preferably 1 to 2, more preferably 1 substituent selected from a phenylcarbonyl group, a phenylvinyl group, a naphthylvinyl group and a methylaminocarbonyl group, Examples include benzothiophene, benzofuran, dibenzothiophene or coumarin.

(Iii) A compound represented by the general formula [1] having a substituent or unsubstituted

Specific examples of the compound represented by the general formula [1] include those having the following structures:

Of these, the following structures are preferred.

  Examples of the substituent of the compound represented by the general formula [1] having a substituent include the same substituents as those of the aromatic hydrocarbon compound. Among these, an alkyl group having 1 to 6 carbon atoms, an alkylcarbonyl group having 2 to 7 carbon atoms, an aryl group having 6 to 10 carbon atoms, and the like are preferable.

The compound represented by the general formula [1] having a substituent is usually 1 to 3, preferably 1 to 2, more preferably, in the benzene ring or 5 to 6-membered cycloalkane of the general formula [1]. Have one. Preferable specific examples thereof include, for example, the following general formulas [1-1] to [1-9].

(In the above formula, R is ethyl group, n-butyl group, n-hexyl group, phenyl group, hydroxyl group, carboxyl group, methylcarbonyl group, tert-butylcarbonyl group, n-butylcarbonyl group, n-propylcarbonyl group. , A phenylcarbonyl group, a phenylvinyl group, a naphthylvinyl group, a methylaminocarbonyl group, or a phenyl group, and when there are two Rs, each may be independently different). Of these, general formulas [1-1], [1-5], [1-8] and the like are preferable.

[ Organic solvent according to the present invention ]
The organic solvent according to the present invention is used as a co-solvent for the solution according to the present invention. By using these, the solubility of the substrate can be improved, and as a result, the deuteration rate can also be improved. Therefore, the organic solvent is preferably used. In particular, when a substrate having low solubility in the solution according to the present invention is used, it is preferable to select and use an appropriate organic solvent having high solubility of the substrate.

  Examples of the organic solvent include alcohols such as methanol, ethanol, pentanol, and hexanol, n-hexane, n-heptane, n-octane, n-nonane, n-decane, cyclohexane, cycloheptane, cyclooctane, cyclononane, and cyclodecane. Of these, alkane compounds such as toluene and the like are preferable. Among them, alkane compounds in which the solvent itself is hardly oxidized or deuterated are preferable, n-hexane and cyclohexane are more preferable, and cyclohexane is particularly preferable.

  The amount of the organic solvent used may be an amount that can dissolve the substrate, but is usually 1 to 100 mL, preferably 1 to 10 mL, relative to 1 mmol of the substrate. Moreover, 0.1-200 mL is normally used with respect to 1 mL of solutions based on this invention, Preferably 1-100 mL is used.

[Deuteration method of the present invention]
In the deuteration method according to the present invention, in the presence of the solution according to the present invention and the catalyst according to the present invention, a deuterium source and an aromatic compound are contacted to react with each other so that a hydrogen atom in the aromatic compound is deuterated. It is made by making it. Depending on the type of substrate, an organic solvent may be added and reacted.

  The reaction time of the deuteration reaction according to the present invention is usually 1 to 50 hours, preferably 1 to 24 hours, more preferably 2 to 5 hours. The reaction temperature is usually 20 to 100 ° C., preferably 70 to 100 ° C., and the deuteration reaction can proceed even if the temperature does not exceed 100 ° C. as in the conventional deuteration method. The pressure during the reaction may be normal pressure to 1 MPa, but is preferably normal pressure. The deuteration reaction is preferably performed in an inert atmosphere such as an argon atmosphere or a nitrogen atmosphere.

  The deuteration method of the present invention is specifically performed as follows, for example. That is, 1 mmol of the aromatic compound according to the present invention as a substrate and 0.03 mmol of platinum carbon, for example, are mixed in a mixed solution of 4 to 8 mL of 2-propanol, 2-butanol or / and 3-pentanol and 4 to 8 mL of heavy water. In addition, the reaction system is purged with argon and then reacted at 100 ° C. for 1 to 24 hours. As a result, light hydrogen in the aromatic compound as a substrate can be deuterated.

  In the deuteration method of the present invention, it is preferable that all the light hydrogen bonded to the aromatic ring in the aromatic compound is deuterated, but all or part of the light hydrogen in the substituent is deuterated. It may be hydrogenated.

  The present invention will be described more specifically with reference to the following examples. However, the present invention is not limited to these examples.

The deuteration rates in the examples and comparative examples were determined as follows.
That is, after completion of the predetermined reaction, the reaction solution was extracted with ether, the catalyst was filtered, the filtrate was concentrated under reduced pressure, and then an appropriate internal standard substance [durene (1,2,4,5-tetramethylbenzene), benzene , Acetone, acetonitrile, dioxane, dimethyl sulfoxide, dichloromethane, etc.) were added, and ¹ H-NMR, ² H-NMR and Mass spectra were measured for structural analysis. Based on the results, the position of deuterated hydrogen was identified, and the deuteration rate of the hydrogen atom of the reaction substrate was determined.

Examples 1-3. Comparative Examples 1-5. Study of catalyst activation solvent in deuteration reaction

  To a 20 ml test tube, add 38.5 mg (0.25 mmol) of biphenyl, 14.6 mg (0.0075 mmol, 3 mol%) of 10% platinum carbon (Pt / C), 2 ml of the solvent listed in Table 1, and 1 ml of heavy water (55.27 mmol). The reaction system was purged with argon, and stirred at 100 ° C. for 24 hours. The 10% platinum carbon means that 10% platinum is contained in the platinum carbon, and mol% in parentheses is platinum carbon containing 3 mol% platinum with respect to the reaction substrate. Means that. The same applies hereinafter. After completion of the reaction, ether was added, the catalyst was filtered using a membrane filter (Millex-LH 0.45 μm), and the filtrate was extracted with ether. The obtained ether layer was washed with water, dried over sodium sulfate, and concentrated under reduced pressure to quantitatively obtain the desired deuterium compound.

  These results are shown in Table 1. The deuteration rates (1) to (3) represent the hydrogen deuteration rates of the reaction substrates (1) to (3) in the table.

  As is clear from the results in Table 1, only 2-propanol, 2-butanol and 3-pentanol activate the platinum catalyst and perform a deuteration reaction with a high deuteration rate of 75% or more. I found that I can do it.

Examples 4-7. Examination of catalyst activation solvent amount in deuteration of biphenyl

  Biphenyl dehydration reaction was carried out in the same manner as in Example 1 except that the reaction was carried out using a predetermined amount of 2-propanol and heavy water shown in Table 2, and the desired deuterium compound was quantitatively obtained. It was. These results are shown in Table 2. In addition, (1)-(3) in a table | surface represents the deuteration rate of the same position as hydrogen in the biphenyl of Table 1.

  From the results in Table 2, when deuterating 0.25 mmol of biphenyl, 0.5 ml (6.54 mmol; approximately 870 times mol of platinum catalyst) and 1 ml of heavy water (55.27 mmol; relative to the amount of hydrogen in the substrate) It was found that deuteration proceeds at a deuteration rate of 85% or more when used in excess of 22.1 mol).

Examples 8-15. Examination of cosolvent in deuteration of biphenyl

  In Examples 8 to 11, the reaction of biphenyl was performed in the same manner as in Example 5 except that 0.1 ml of 2-propanol and 0.9 ml of the cosolvent shown in Table 3 were used instead of 1 ml of 2-propanol. A deuteration reaction was performed to quantitatively obtain the desired deuterium compound. In Example 12, biphenyl deuteration was carried out in the same manner as in Example 5 except that 0.01 ml of 2-propanol and 0.99 ml of cyclohexane were used instead of 1 ml of 2-propanol. Was obtained quantitatively.

In Examples 13 to 15, instead of 1 ml of 2-propanol, 1 ml of 2-propanol and 9 ml or 3 ml of the cosolvent shown in Table 3 were used, 40 ml instead of 2 ml of heavy water, and 38.5 mg of biphenyl. Instead, deuteration of biphenyl was carried out in the same manner as in Example 5 except that 385 mg (2.5 mmol) was reacted using 146 mg instead of 14.6 mg of 10% platinum carbon (Pt / C). The target deuterium compound was quantitatively obtained.

  These results are shown in Table 3. In addition, (1)-(3) in a table | surface represents the deuteration rate of the same position as hydrogen in the biphenyl of Table 1.

Example 16. Biphenyl deuteration using cyclohexane as co-solvent for 3-pentanol . Biphenyl was prepared in the same manner as in Example 9 except that 0.1 ml of 3-pentanol was used instead of 0.1 ml of 2-propanol. The target deuterium compound was quantitatively obtained.

  The results are shown in Table 3 together with Examples 8-15. In addition, (1)-(3) in a table | surface represents the deuteration rate of the same position as hydrogen in the biphenyl of Table 1.

  From the results of Examples 8 to 15, when various co-solvents shown in Table 3 are used, even if the amount of 2-propanol which is an activation solvent for the platinum catalyst is reduced (Examples 8 to 11 and Examples 13 to 15). Was about 170 times mol with respect to the platinum catalyst and Example 12 was about 17 times mol), indicating that the deuteration reaction proceeds. It was also found that when cyclohexane, which is the least susceptible to deuteration, was used as a cosolvent, the reaction proceeded at a deuteration rate of 90% or higher, and the deuteration rate was higher than when no cosolvent was used. . Furthermore, even when 3-pentanol was used instead of 2-propanol, it was found that when cyclohexane was used as a cosolvent, the deuteration rate was improved compared to the case where no cosolvent was used. .

  When such a co-solvent is used, even a substrate that is difficult to dissolve in 2-propanol or 3-pentanol can be deuterated, so that various reaction substrates can be deuterated.

Examples 17-20. Comparative Example 6 Examination of catalyst species in deuteration of biphenyl

  Biphenyl deuteration was carried out in the same manner as in Example 9 except that the reaction shown in Table 4 was used, and the target deuterium compound was quantitatively obtained. These results are shown in Table 4 together with the results of Example 9. In addition, (1)-(3) in a table | surface represents the deuteration rate of the same position as hydrogen in the biphenyl of Table 1.

  From the results in Table 4, it was found that a platinum catalyst was most effective for this reaction. It was found that the platinum catalyst may or may not be supported on activated carbon or alumina, and the reaction proceeds with a high deuteration rate regardless of whether the valence of platinum metal is 0 or 4. Further, it was found that the deuteration reaction does not proceed with the palladium catalyst, but the reaction proceeds at a moderate deuterium ratio when the rhodium catalyst or the ruthenium catalyst is used.

Example 21. Examination of the amount of platinum catalyst

  Biphenyl was obtained in the same manner as in Example 9, except that 10% platinum carbon (Pt / C) 4.9 mg (1 mol%) was used instead of 10% platinum carbon (Pt / C) 14.6 mg (3 mol%). The target deuterium compound was quantitatively obtained. As a result, the yield was 99%, and the deuteration rate was (1) 25%, (2) 97%, and (3) 97% with respect to the same position as hydrogen in biphenyl in Table 1, respectively.

  From this result, even when the platinum catalyst was reduced to 1 mol% (0.0025 mmol), the meta and para positions of biphenyl [positions (2) and (3)] reacted with a high deuteration rate. Was found to progress.

Examples 22-23. Examination of reaction temperature

  Except that the reaction was carried out at the temperatures and reaction times shown in Table 5, the deuteration reaction of biphenyl was carried out in the same manner as in Example 9 to quantitatively obtain the desired deuterium compound. The results are also shown in Table 5. In addition, (1)-(3) in a table | surface represents the deuteration rate of the same position as hydrogen in the biphenyl of Table 1.

  From the results in Table 5, it was found that the reaction proceeds at a high deuteration rate at the meta and para positions of biphenyl [positions (2) and (3)] even at room temperature.

Examples 24-25. Deuteration reaction with deuterated 2-propanol

Instead of 2 ml of solvent and 1 ml of heavy water, 1 ml of 2-propanol-d ₁ [(CH ₃ ) ₂ CHOD] or 2-propanol-d ₈ [(CD ₃ ) ₂ CDOD] was used at 80 ° C. for 3 hours. Except for carrying out the reaction, the deuteration reaction of biphenyl was carried out in the same manner as in Example 1 to quantitatively obtain the desired deuterium compound.

  These results are shown in Table 6. In addition, (1)-(3) in a table | surface represents the deuteration rate of the same position as hydrogen in the biphenyl of Table 1.

  From the results shown in Table 6, when deuterated 2-propanol is used, deuterated 2-propanol also serves as a deuterium source, and therefore deuterium source such as deuterium does not exist. It was found that the hydrogenation reaction proceeds.

Examples 26-48. Deuteration reaction of various substrates 1

Biphenyl deuteration corresponding to the substrate was carried out in the same manner as in Example 9 except that the substrates shown in Table 7 and Table 8 below were reacted at a predetermined temperature and reaction time.
However, in Example 30, the reaction was conducted in the presence of 10% Pd / C (3 mol%) in addition to 10% Pt / C (3 mol%) as a mixed catalyst. In Example 42, 10% Pt / C (10 mol%) was used instead of 10% Pt / C (3 mol%). In Examples 38, 43, 44 and 46, 10% Pt / C Instead of (3 mol%), 10% Pt / C (15 mol%) was used.

  These results are shown in Tables 7 and 8. The deuteration rate of each hydrogen in Table 7 and Table 8 indicates the deuteration rate of the hydrogen atom at the position of the number appended to the structural formula of each reaction substrate.

* 1 Example 30 10% Pt / C (3 mol%) and 10% Pd / C (3 mol%) used * 2 Example 42 10% Pt / C (10 mol%) used * 3 Example 38 , 43, 44, 46 Use 10% Pt / C (15 mol%)

From the above results, it was found that the deuteration reaction can proceed efficiently in various aromatic compounds although there are variations due to the substrate.
From the results of Examples 29 and 30, it was found that the deuteration rate of the alkyl group portion which is a substituent is improved when the deuteration reaction is carried out in the presence of palladium carbon and platinum carbon. Although palladium carbon does not show catalytic activity in the deuteration reaction (Comparative Example 6), it has been found that the deuteration rate is improved when used as a mixed catalyst.

Examples 49-66. Deuteration reaction of various substrates 2

Using 9 ml of cyclohexane, 1 ml of 2-propanol, 20 ml of heavy water, and 146 mg of 10% platinum carbon (Pt / C), the substrates (2.5 mmol) shown in Table 9 and Table 10 below were reacted at a predetermined temperature and reaction time. The substrate was deuterated in the same manner as in Example 8 except that the above was performed.
However, in Example 64, the amount of 2-propanol used was 0.3 ml.

  These results are shown in Tables 9 and 10. In Tables 9 and 10, the deuteration rate of each hydrogen indicates the deuteration rate of the hydrogen atom at the position of the number appended to the structural formula of each reaction substrate.

* 3 Example 64 Using 0.3 ml of 2-PrOH.

From the above results, it was found that the deuteration reaction can proceed efficiently in various aromatic compounds although there are variations due to the substrate. In particular, the compounds containing sulfur atoms as in Examples 54 to 57 could not be deuterated by the conventional method due to the poisoning action of sulfur atoms, but according to the method of the present invention, deuteration was not possible. I found it going. Also, aromatic compounds having no substituents and aromatic compounds containing fluorine atoms as in Examples 62 to 65 could not be deuterated by the conventional method, but according to the method of the present invention, It was found that deuteration proceeds.
Examples 67-70. Deuteration reaction of various substrates 3

  Substrate deuteration was carried out in the same manner as in Example 9 except that the substrates shown in Table 11 below were reacted at a predetermined temperature and reaction time.

  These results are shown in Table 11. The deuteration rate of each hydrogen in Table 11 indicates the deuteration rate of the hydrogen atom at the position of the number appended to the structural formula of each reaction substrate.

  From the above results, it was found that according to the method of the present invention, even in the case of benzene having a silanol group, a sulfonyl group, a sulfonyloxy group, or a phosphoryl group, deuteration of hydrogen in benzene can be promoted efficiently. . understood

  As described above, according to the method of the present invention, light hydrogen in various aromatic compounds can be deuterated without using hydrogen gas or deuterium gas. Further, unlike the conventional method, deuteration can be achieved without reducing the carbonyl group or the double bond, so that the desired deuterated compound can be easily obtained.

Claims (10)

2-propanol, contact at least one solvent selected from 2-butanol and 3-pentanol, in the presence of platinum catalysts, the heavy hydrogen source and an aromatic compound selected from heavy water and deuterated solvents A method for deuterating an aromatic compound, characterized by comprising: The method according to claim 1, wherein a hydrogen atom of an aromatic ring in the aromatic compound is deuterated. The method of Claim 1 or 2 which makes a deuterium source and an aromatic compound contact at 20-100 degreeC. The method according to claim 1, wherein the platinum catalyst is platinum carbon, platinum alumina, or platinum oxide. Said platinum catalysts, in the presence of different platinum group catalyst with the catalyst, contacting a heavy hydrogen source and an aromatic compound, The method according to any of claims 1-4. The method according to claim 5 , wherein the platinum group catalyst is a platinum catalyst, a palladium catalyst, a rhodium catalyst, a ruthenium catalyst, a nickel catalyst, or a cobalt catalyst. Aromatic compound is an alkyl group having 1 to 6 carbon atoms, an alkoxy group having a carbon number of 1-6, an aryl group having 6 to 10 carbon atoms, a hydroxyl group, an amino group, a carboxyl group, a halogeno group, an alkoxy of 2-7 carbon atoms Carbonyl group, alkyl carbonyl group having 2 to 7 carbon atoms, aryl carbonyl group having 7 to 11 carbon atoms, aryl alkenyl group having 8 to 13 carbon atoms, aryloxyalkyl group having 7 to 13 carbon atoms, and 8 to 14 carbon atoms An arylcarbonyloxyalkyl group, an alkylaminocarbonyl group having 2 to 10 carbon atoms, an alkylcarbonylamino group having 2 to 10 carbon atoms, an alkylcarbonylalkenyl group having 4 to 7 carbon atoms, an alkylcarbonylalkyl group having 4 to 7 carbon atoms, diaryl silanol group having 12 to 20 carbon atoms, an arylsulfonyl group having 6 to 10 carbon atoms, alkylene having a carbon number of 1 to 6 Sulfonyloxy groups, and having 1-2 substituents selected et or alkylphosphoryl alkyl group having 2 to 12 carbon atoms, an aromatic hydrocarbon compound, represented by an aromatic heterocyclic compound, or the following general formula [1] Compound
(Wherein A represents a 5- to 6-membered cycloalkane in which 1 to 3 methylene groups may be substituted with a carbonyl group or / and a group represented by -O-),
Alternatively, the method according to any one of claims 1 to 6 , which is an unsubstituted aromatic hydrocarbon compound, an unsubstituted aromatic heterocyclic compound, or an unsubstituted compound represented by the above general formula [1]. The method according to any one of claims 1 to 7 , wherein the deuterium source is heavy water. Furthermore, the method in any one of Claims 1-8 which uses an organic solvent as a cosolvent . The method according to claim 9 , wherein the organic solvent is selected from alcohols, alkane compounds, and toluene, excluding 2-propanol, 2-butanol and 3-pentanol.