WO2007083696A1

WO2007083696A1 - Method for production of thiazole-substituted acetonitrile

Info

Publication number: WO2007083696A1
Application number: PCT/JP2007/050685
Authority: WO
Inventors: Yoshiyuki Kusuoka; Hideaki Suzuki; Norio Tanaka
Original assignee: Nissan Chemical Industries, Ltd.
Priority date: 2006-01-18
Filing date: 2007-01-18
Publication date: 2007-07-26
Also published as: JP2009084156A

Abstract

[PROBLEMS] To provide a process for producing a thiazole-substituted acetonitrile compound with good efficiency. [MEANS FOR SOLVING PROBLEMS] Disclosed is a process for producing a thiazole-substituted acetonitrile compound (2) represented by the formula (2). The process comprises the step or reacting a halomethylthiazole compound represented by the formula (1) with potassium cyanide or sodium cyanide under heating in a two-phase system which is composed of an organic solvent immiscible with water and water and contains a phase transfer catalyst: (1) wherein Q represents an unsubstituted or substituted thiazolyl group; and X represents a halogen atom]; and (2) wherein Q is as defined above.

Description

Process for the production of thiazole-substituted acetonitrile

Technical field

[0001] The present invention relates to a method for producing a thiazole-substituted acetonitrile compound useful as an agricultural pharmaceutical intermediate.

Background art

[0002] For the production of heterocyclic substituted acetonitriles, a halomethyl heterocyclic compound is reacted with cyanogen sodium and potassium cyanide in a polar solvent miscible with water such as dimethyl sulfoxide, dimethylformamide, dimethylacetamide, ethanol and methanol. There are widely known examples of the reaction method, or addition of crown ethers such as 18 crown 6 ether, cryptands, and the like to the above-described system. On the other hand, the example in which the above reaction is carried out in a two-phase system of an organic solvent immiscible with water and water, as seen in Non-Patent Document 1, is limited to compounds having a thiophene ring, methylene chloride, aqueous system, phase transfer. There is a system that uses triethyl benzyl diammonium bromide as a catalyst. In addition, as shown in Patent Document 1, an example in which a phase transfer catalyst is used in a two-phase system of a substrate and water without using a solvent for a compound having a thiophene ring is also known. In Patent Document 2, a substrate is a dimethylaminomethyl heterocyclic compound in which a substrate is connected with a heterocycle of a halomethyl compound, and cyanide in a two-phase system of toluene and water is known. Patent Document 3 shows an example in which a phase transfer catalyst is used in a two-phase system of a halomethylimidazole compound with a black mouth form and water. Non-patent documents 2 and 3 have examples of 2-phenyl-4-cyanomethylthiazole using cyanate sodium and ethanol, but industrially, solvent exchange is disadvantageous and the yield is also improved to 81 percent. There is room for. Thus, there is no description of a system in which a halomethylthiazole compound is not miscible with water and is cyanated using a phase transfer catalyst in a two-phase system of an organic solvent and water.

Patent Document 1: International Publication No. 2002Z094806 Pamphlet

Patent Document 2: Japanese Patent Laid-Open No. 52-14764

Patent Document 3: Japanese Patent Laid-Open No. 57-98270

Non-patent literature l: Yaoxue Xuebao 1992, No. 27, No. 4, p. 261 Non-Patent Document 2: Yoichi Bian Journal of Medicinal Chemistry, 1974, No. 9, No. 4, p. 445

Non-Patent Document 3: Journal of American Chemical Society, 1943, 65th, 1667

Disclosure of the invention

Problems to be solved by the invention

[0003] As described above, a simple, efficient and more industrially advantageous production method has not been found for thiazole-substituted acetonitrile compounds useful as an agricultural pharmaceutical intermediate.

Means for solving the problem

[0004] The present inventors have made extensive studies in view of such a situation, and as a result, the halomethylthiazole compound was used in a system in which an organic solvent not mixed with water and a two-phase system of water and a phase transfer catalyst were added. A method characterized by reacting with sodium halide or potassium cyanide under heating was found, and the present invention was completed.

That is, the present invention

(1) Equation (1):

[Chemical 1]

Q― CH ₂ X (1)

[Wherein Q is substituted with G !, may! /, Is a thiazolyl group,

X is a halogen atom,

G is a halogen atom, C 1 -C alkyl group, C—C cyanoalkyl group, halogen atom

1 10 2 4

Or a C C alkyl substituted with a phenyl group which may be substituted with a C C alkyl group.

1 4 1 4 alkyl group, C—C alkyl group, C—C alkyl group, C—C haloalkyl group, C

2 5 2 6 1 6 2

—C haloalkyl group, C—C haloalkyl group, C—C halocycloalkyl group, C

6 2 6 3 6

A C—C cycloalkyl group optionally substituted with a —C alkyl group, a C—C alkoxy group;

1 3 3 6 1 10 Si group, C—C alkoxy group, C—C alkyloxy group, C—C haloalkoxy group

2 6 2 6 1 4 Xoxy group, C—C haloalkoxy group, C—C haloalkyloxy group, C—C Alkylsulfuric group, C—C alkylsulfier group, C—C alkylsulfo group

1 4 1 4

Group, C—C alkylsulfur group, C—C alkylsulfur group, C—C

2 6 2 6 2 Alkylsulfonyl group, C—C alkynylsulfur group, C—C alkynyl group

6 2 6 2 6

Rufyl group, C—C alkynylsulfol group, C—C haloalkylsulfur group

2 6 1 4

Group, C—C haloalkylsulfier group, C—C haloalkylsulfol group, C—C

1 4 1 4 2 Noroanoreke-Noresnolehue-Nole group, C—C haloanoreke-Nolesnorephi-Nore group, C—Chalo

6 2 6 2 6 Anoleke-norethnoreno-nole group, C—C haloanole-norethnolenoe-nore group, C—C noroanore group

2 6 2 6 Quinylsulfuryl group, C—C haloalkynylsulfol group, CHO, NO, CN, O

2 6 2

H, naphthyl group, halogen atom or C—C alkyl group may be substituted.

14

A methoxy group substituted with a ethyl group, a C—C alkoxycarbo group, a C—C alkoxy group

2 5 2 4 Sialkyl group, C C alkyl carbonyl group, C C haloalkyl carbo group,

2 4 2 4

C C alkyl carboxy-oxy group, C C haloalkyl carboxy-oxy group, C

2 5 2 5 3

—C dialkylaminocarboxoxy group, phenyl group optionally substituted by Z, Z

7

A phenoxy group which may be substituted with Z, a benzoyl group which may be substituted with Z, a pyridyl group which may be substituted with Z, a pyridyloxy group which may be substituted with Z, However, a chael group, a methylenedioxy group bonded at an adjacent substitution position, a bonded halomethylenedioxy group bonded at an adjacent substitution position, and N = CT'T ² (where T ¹ and T ² are Each independently H, phenyl, benzyl or C—C alkyl

It may form a 5-membered ring, a 6-membered ring, a 7-membered ring or an 8-membered ring with the carbon atom to which the forces T ¹ and T ² which are 16 groups are bonded. ) Is a substituent arbitrarily selected from the above (provided that when there are two or more substituents, they may be the same or different from each other), and the number of the substituents is 1 or 2 Or a 5-membered ring, 6-membered ring, 7-membered ring or 8-membered ring formed by an alkylene group bonded at adjacent substitution positions,

Z is a halogen atom, C—C alkyl group, C—C haloalkyl group, C—C alkoxy

1 4 1 4 1 4 group, C—C haloalkoxy group, C—C alkylsulfur group, C—C alkyl group

1 4 1 4 1 4

Rufyl group, C—C alkylsulfol group, C—C alkylsulfur group, C

1 4 2 5 2

— C-alkulsulfyl group, C— C-alkylsulfol group, C—C haloal group

5 2 5 1 4 Kill sulfo group, NO, CN, CHO, OH, -NU ^J U ² , phenol group, phenoxy group Or the intermediate force of a c-c alkoxycarbo group.

twenty five

When two or more substituents are present, they may be the same or different from each other. ) And the number of substituents is 1, 2, 3, 4 or 5,

U ¹ and U ² are each independently H, C—C alkyl group, C—C alkyl carbo-

1 6 2 5

A force representing a ruthenium group, a phenol group or a benzyl group, and a 5-, 6-, 7-, or 8-membered ring can be formed together with the carbon atom to which u ¹ and u ² are bonded. Good. ]

Is reacted with cyanide sodium or cyanide potassium in a system that is not mixed with water and that contains a two-phase organic solvent and water and a phase transfer catalyst. Characterize

Formula (2)

[Chemical 2]

Q— CH ₂ CN (2)

(Wherein Q represents the same meaning as described above), a method for producing a thiazole-substituted acetonitrile compound represented by:

[2] A process for producing a thiazole-substituted acetonitrile compound represented by formula (2) according to [1], wherein Q is a 2-furthiazole-4-yl group,

[3] The method for producing a thiazole-substituted acetonitrile compound represented by the formula (2) according to [1], wherein the phase transfer catalyst is tetraptyl ammonium halide, and the reaction solvent is toluene or heptane, and

[4] The Q is a 2-phenylthiazol-4-yl group, the phase transfer catalyst is tetrabutylammonium halide, and the reaction solvent is toluene or heptane. [1] This is a method for producing a thiazole-substituted acetonitrile compound.

The invention's effect

According to the production method of the present invention, a thiazole-substituted acetonitryl compound that is important as an intermediate for producing agricultural medicine can be easily produced in an industrially suitable manner.

BEST MODE FOR CARRYING OUT THE INVENTION In the present invention, Q represents a thiazole-2-yl group, a thiazole-4-yl group or a thiazol-5-yl group.

The halogen atom in the definition of G includes a fluorine atom, a chlorine atom, a bromine atom and an iodine atom, preferably a fluorine atom, a chlorine atom and an iodine atom.

The alkyl group in the definition of G, U ¹ , U ² or Z is a linear or branched alkyl group such as methyl group, ethyl group, n propyl group, isopropyl group, n butyl group, isobutyl group, tert butyl Group, sec butyl group, pentyl 1 group, pentyl 2 group, pentyl 3 group, 2-methylbutyl 1 group, 2-methylbutyl 2 group, 2 methylbutyl 3 group, 3-methylbutyl 1 group, 2, 2 dimethylpropyl 1 group, 1 hexyl, 2 hexyl, 3 hexyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1,1-dimethylbutyl, 1,2 dimethylbutyl, 1,3 dimethyl Butyl group, 2,2 dimethylbutyl group, 2,3 dimethylbutyl group, 3,3 dimethylbutyl group, 1 ethylbutyl group, 2 ethylbutyl group, 1,1,2-trimethyl Rupropyl group, 1, 2, 2-trimethylpropyl group, 1-ethyl-1-methylpropyl group, 1-ethyl-2-methylpropyl group, n-heptyl group, n-octyl group, n-nonyl group, n-undecyl Group, n-dodecyl group, n-tridecyl group, n-tetradecyl group, n pentadecyl group, n-hexadecyl group, n-heptadecyl group, n-octadecyl group, _n- nonadecyl group, _n -icosyl group, etc. Each selected within the specified number of carbon atoms.

The alkenyl group in the definition of G includes a straight-chain or branched alkenyl group such as an etul group, a 1-probe group, a 2-probe group, a 1-butur group, a 2-butur group, and a 3-butyl group. , 1-methyl-2-propellyl group, 2-methyl-2-propellyl group, 1-pentale group, 2-pentale group, 3-pentale group, 4-pentale group, 1-methyl-2-buturel group , 2-Methyl-2-Butyl group, 3-Methyl-2-Butul group, 1-Methyl-3-Butul group, 2-Methyl-3 Butyl group, 3-Methyl-3 Butyl group, 1,1 Dimethyl-2-Butyl group, 1, 2 —Dimethyl-2-propellyl group, 1-ethyl-2-propellyl group, 1-hexyl group, 2-hexyl group, 3-hexyl group, 4 1-hexyl group, 5 hexyl group, 1-methyl-2-pental group, 2-methyl-

2 Pentayl group, 3-Methyl-2 Pentayl group, 4-Methyl-2 Pentayl group, 1-Methyl-3 Pentayl group, 2-Methyl-3 Pentayl group, 3-Methyl-3 Pentayl group, 4-Methyla 3 pent - group, 1-methyl-4 pent - group, 2-methylcarbamoyl Lou ₄ pent - group, _{_3-methyl-4} pent - group, _{_4-methyl-4} pent - group, 1, 1-dimethyl-2 Buteyuru group, 1 , 1-dimethyl-3 butyl group, 1,2 dimethyl-2 butur group, 1,2 dimethyl-3 butur group, 1,3 dimethyl-2-butur group, 1,3 dimethyl-3 butur group, 2,3 dimethyl-2 butur group, 2,3 Dimethyl-3 butyl group, 3,3 Dimethyl-2 butur group, 1-ethyl-2-buturyl group, 1-ethyl-3 butur group, 2-ethyl-2-buturyl group, 2-ethyl-3-butyr group, 1,1,2 trimethyl 2-pro Bale group 1 Echiru 1 over main Chiru 2 Purobe - Le group and the like, Ru is selected each specified range power of the number of carbon atoms.

The alkynyl group in the definition of G includes a ethynyl group, a 1-propynyl group, a 2-propynyl group, a 1-butynyl group, a 2-butynyl group, a 3-butyl group, and a 1-methyl-2 as a linear or branched alkyl group. Propyl group, 1 pentyl group, 2-pentyl group, 3 pentyl group, 4 pentyl group, 1-methyl-2-buturyl group, 1-methyl-3 butyl group, 2-methyl-3 petit group Group, hexyl group, 1-methyl-3-pentyl group, 1-methyl-4 pentyl group, 2-methyl-3 pentyl group, 2-methyl-4 pentyl group, 3-methyl-4 pentyl group Group, 4-methyl-2-pentyl group, 1,1 dimethyl-2-propyl group, 1,1 dimethyl-3-propyl group, 1,2 dimethyl-3 butyl group, 2,2 dimethyl-3 pentyl group Groups, 1-ethyl-2-butyl, 1-ethyl 3-butulyl, 2-ethyl -3 Butul group, etc., each selected from the range of the specified number of carbon atoms.

The haloalkyl group in the definition of G or Z includes a linear or branched haloalkyl group such as a fluoromethyl group, a chloromethyl group, a bromomethyl group, a fluorethyl group, a chloroethyl group, a bromoethyl group, a fluoro- _n -propyl group, and a chloro- _n group. —Propyl group, difluoromethyl group, chlorodifluoromethyl group, trifluoromethyl group, dichloromethyl Group, trichloromethyl group, difluoroethyl group, trifluoroethyl group, trichloroethyl group, chlorodifluoroethyl group, bromodifluoromethyl group, trifluorochloroethyl group, hexafluoro-n-propyl group, chlorobutyl group , Fluorobutyl group, black end-n-pentyl group, fluoro-n-pentyl group, black end n-hexyl group, fluoro-n-hexyl group, etc. .

[0008] C -C cycloalkyl optionally substituted with C -C alkyl group in the definition of G

1 3 3 6

Cyclopropyl group, 1-methylcyclopropyl group, 2, 2, 3, 3, —tetramethylcyclopropyl group, cyclobutyl group, 1-ethylcyclobutyl group, 1 n-butyl cyclobutyl group, cyclopentyl Group, 1-methylcyclopentyl group, cyclohexyl group, 1-methylcyclohexyl group, 4-methylcyclohexyl group and the like.

Optionally substituted with a halogen atom in the definition of G or a C C alkyl group

14

The C—C alkyl group substituted with a phenol group includes a benzyl group and 2-chlorobenzene.

14

Group, 3-bromobenzyl group, 4-chlorobenzyl group, 4-methylbenzyl group, 4-tert-butylbenzyl group, 1-phenylethyl group, 1- (3-chlorophenyl) ethyl group, 2 —Phenyl-ethyl group, 1-methyl-1-phenyl-phenyl group, 1- (4-phenyl) 1-methylethyl group, 1- (3-phenyl)-1-methylethyl group, 1 —Phenylpropyl group, 2-phenylpropyl group, 3-phenylpropyl group, 1-phenylbutyl group, 2-phenylbutyl group, 3-phenylbutyl group, 4-phenolbutyl group, 1-methyl-1-phenol Rupropyl group, 1-methyl-2-phenylpropyl group, 1-methyl-3-phenolpropyl group, 2-methyl-2-phenolpropyl group, 2- (4-chlorophenol) 2-methyl group pill group, 2 -Methyl-2- (3 methylphenol) propyl group.

[0009] The alkoxy group in the definition of G or Z includes a straight chain or branched alkoxy group such as a methoxy group, an ethoxy group, an n propoxy group, an isopropoxy group, an n butoxy group, an isobutoxy group, a sec butoxy group, and a tertiary group. Butoxy group, n-pentyloxy group, 1-methylbutoxy group, 2-methylbutoxy group, 3-methylbutoxy group, 1,1-dimethylpropoxy group, 1,2-dimethylpropoxy group, 2,2-dimethylpropoxy group Xyl group, 1-ethylpropyloxy group, n-hexyloxy group, 1-methylpentylo Xy group, 2-methylpentyloxy group, 3-methylpentyloxy group, 4-methylpentyloxy group, 1,1-dimethylbutoxy group, 1,2-dimethylbutoxy group, 1,3 dimethylbutyloxy group Xy group, 2,2 dimethyl butyloxy group, 2,3 dimethyl butyloxy group, 3,3 dimethyl butyloxy group, 1 ethyl butyloxy group, 2 butyl butyloxy group, 1, 1,2-trimethylpropyl Xyl group, 1, 2, 2, -trimethylpropyloxy group, 1-ethyl-1-methylpropyloxy group, 1-ethyl-2-methylpropyloxy group, n-heptyloxy group, n-octyloxy group, n-noroxy group, n includes a decyloxy group, etc., each selected from a range of the specified number of carbon atoms.

The C 1 -C halocycloalkyl group in the definition of G includes a fluorocyclopropyl group

3 6

, Difunole, rocyclopropinole group, cucyclopropinole group, dichroic cyclopropinole group, 1-methylolene 2,2-dichlorocyclopropinole group, chlorocyclobutinole group, dichlorocyclobutyl group, chlorocyclopentyl group, dichlorocyclopentyl group Chlorocyclohexyl group, dichlorocyclohexyl group, tetrafluorocyclobutyl group and the like.

One Nl ^ U ² in the definition of G or Z includes methylamino group, ethylamino group, n-propylamino group, isopropylamino group, n-butylamino group, isobutylamino group, sec-butylamino group, tertiary butylamino group. , N-pentylamino group, 1-methylbutylamino group, 2-methylbutylamino group, 3-methylbutylamino group, 1,1-dimethylpropylamino group, 1,2-dimethylpropylamino group, 2,2-dimethylpropyl group Amino group, 1-ethylpropylamino group, n-hexylamino group, 1-methylpentylamino group, 2-methylpentylamino group, 3-methylpentylamino group, 4-methylpentylamino group, 1, 1-Dimethylolebutinoreamino group, 1,2 Dimethinolevbutenoreamino group, 1,3 Dimethinolevinoreamino group, 2,2 Dimethinole Butinoreamino group, 2,3 Dimethinolebutinoreamino group, 3,3-Dimethylbutylamino group, 1-Ethylbutylamino group, 2-Ethylbutylamino group, 1,1,2-Trimethylpropylamino 1, 2, 2-trimethylpropylamino group, 1-ethyl 1-methylpropylamino group, 1-ethyl-2-methylpropylamino group, dimethylamino group, jetylamino group, di-n-propylamino group, diisopropylamino group, n—Butylamino group, di-sec Butylamino group, diisobutylamino group, di-n-pentyl Amino group, di-n-hexylamino group, methylethylamino group, methylpropylamino group, methylisopropylamino group, methylbutylamino group, methyl-sec-butylamino group, methylisobutylamino group, methyltertiary Butylamino group, Methylpentylamino group, Methylhexylamino group, Ethylpropylamino group, Ethylisopropylamino group, Ethylbutylamino group, Ethyl sec-Butylamino group, Ethylisobutylamino group, Ethyl Pentylamino group, Ethylhexylamino group, Phenylamino group, Benzylamino group, N-Methylacetamide group, N-Ethylacetamide group, N-Phenylacetamide group, N-acetylethylamide group Each is selected within the range of the specified number of carbon atoms.

The C—C alkoxycarbo group in the definition of G and Z includes methoxycarbo

twenty five

Nyl group, ethoxycarbonyl group, n-propoxycarbonyl group, isopropoxycarbonyl group, n-butoxycarbonyl group, sec-butoxycarbonyl group, isobutoxycarbonyl group, tertiary butoxycarbonyl Groups and the like.

As the C—C haloalkoxy group in the definition of G and Z, C—C straight chain or

1 4 1 4 includes branched haloalkoxy groups, such as fluoromethoxy group, difluoromethoxy group, trifluoromethoxy group, chlorodifluoromethoxy group, bromodifluoromethoxy group, dichlorofluoromethoxy group. Group, chloromethoxy group, dichloromethoxy group, trichloromethoxy group, bromomethoxy group, fluoroethoxy group, black ethoxy group, bromoethoxy group, difluoroethoxy group, trifluoroethoxy group, tetrafluoroethoxy group, pentafluoro group Examples include roethoxy group, trichloroguchi ethoxy group, trifluorochloro ethoxy group, fluoropropoxy group, chloropropoxy group, bromopropoxy group, fluorobutoxy group, chlorobutoxy group, fluoroisopropoxy group, and chloroisopropoxy group. .

The C—C alkyl sulfier group in the definition of G and Z includes methyl sulfi

14

-Butyl group, ethylsulfuryl group, n-propylsulfuryl group, isopropylsulfuryl group, n-butylsulfuryl group, isobutylsulfuryl group, sec-butylsulfuryl group, tertiary butylsulfuryl group Can be mentioned.

As the C—C alkylsulfol group in the definition of G or Z, methylsulfo-

14

Group, ethylsulfol group, n-propylsulfol group, isopropylsulfol group, Examples thereof include n-butylsulfol group, isobutylsulfol group, sec butylsulfol group, and tertiary butylsulfol group.

[0012] The C 1 -C alkoxyalkyl group in the definition of G includes C 1 -C alkoxy-methyl

2 4 1 3

Group, C C alkoxyethyl group, methoxyethoxymethyl group and methoxypropyl group

1 2

And the like.

[0013] The C—C alkyl carbo ol group in the definition of G, U ¹ or U ² includes acetyl

twenty four

Group, propiol group, butanol group, isobutanol group and the like.

The C—C alkylcarbo-loxy group in the definition of G, U ¹ or U ² includes

twenty four

Examples thereof include a thioloxy group, a propio-loxy group, a butanoyloxy group, and an isobutanoyloxy group.

[0014] The C—C haloalkyl carbo group in the definition of G includes a chloroacetyl group,

2 6

Examples thereof include a rifluoroacetyl group, 3, 3, 3-trifluorofluoro group, and pentafluoropropionyl group.

The C—C haloalkylcarboxoxy group in the definition of G includes chloroacetyl

twenty five

Examples include a ruoxy group, a trifluoroacetyloxy group, a 3, 3, 3-trifluoropropio-loxy group, a pentafluoropropionyloxy group, and the like.

As the C—C dialkylaminocarboxoxy group in the definition of G, dimethyla

3 7

Examples thereof include a minocarboxoxy group, a jetylaminocarboxoxy group, and a diisopropylaminocarbonyloxy group.

In the definition of G, substituted with Z !, may! /, As the pyridyl group, may be substituted with Z! 2 pyridyl group, substituted with Z, 3 pyridyl group Or substituted with Z !, may include a 4-pyridyl group, preferably substituted with Z, may be substituted with 2 pyridyl group or Z, may be a 3-pyridyl group More preferably, it is a 2-pyridyl group optionally substituted by Z.

Substituted with Z in the definition of G !, may! /, As a pyridyloxy group, substituted with Z, may be 2 pyridyloxy group, substituted with Z !, may! /, A 3-pyridyloxy group substituted with Z may be a 4-pyridyloxy group.

Substituted with Z in the definition of G !, may! /, As a chaer group, substituted with Z! And an optionally substituted 2 chaer group and an optionally substituted 3 chaer group.

N: ^ ¹ ! ^ In the definition of G means an alkylideneamino group, a benzylideneamino group, an arylideneamino group or a cycloalkyldenamino group, a methylideneamino group, a 4-methyl-2-pentylidenamino group, And cyclopentylideneamino group.

The C—C cyanoalkyl group in the definition of G includes a cyanomethyl group, 2-cyanoe

twenty five

Examples thereof include a til group, a 3-cyanopropyl group, and a 1-cyano-1-methylethyl group.

14

Examples of the methoxy group substituted with a phenyl group include benzyloxy group, 2-chloro benzyloxy group, 3-chloro benzyloxy group, 4-chloro benzyloxy group, 3-methylbenzyloxy group, and 4-tert-butylbenzyl. Examples thereof include an oxy group, a 2,6 difluorine benzoyloxy group, and a 2 fluoro 4-chloro benzyloxy group.

A haloalkylsulfur group in the definition of G or Z includes a C—C straight chain or

1 4 As branched or branched haloalkylthio groups, fluoromethylthio group, chlorodifluoromethylthio group, bromodifluoromethylthio group, trifluoromethylthio group, trichloromethylthio group, 2, 2, 2-trifluoro Examples include a chloroethylthio group, 1,1,2,2-tetrafluoroethylthio group, fluorethylthio group, pentafluoroethylthio group and fluoroisopropylpropyl group.

A haloalkylsulfier group in the definition of G or Z includes a C—C straight chain.

1 4 or branched haloalkynylsulfuryl groups include fluoromethylsulfuryl group, chlorodifluoromethylsulfuryl group, bromodifluoromethylsulfuryl group, trifluoromethylsulfuryl group. Group, trichloromethylsulfuryl group, 2,2,2-trifluoroethylsulfuryl group, 1,1,2,2-tetrafluorosulfuryl group, fluoroethylsulfuryl group, pentafluoro Examples thereof include a loetyl sulfyl group and a fluoroisopropyl sulfiel group.

As the haloalkylsulfonyl group in the definition of G or Z, C—C straight chain or

14 is a branched haloalkylsulfol group such as a fluoromethylsulfol group, a chlorodifluoromethylsulfol group, a bromodifluoromethylsulfol group, or a trifluoromethyl group. Sulfo group, trichloromethyl sulfo group, 2,2,2-trifluoroethyl sulfo group, 1, 1, 2, 2-tetrafluoro ethyl sulfo group, fluoro ethyl sulfo group -Luyl group, pentafluoroethylsulfol group, fluoroisopropylsulfol group and the like.

[0016] The haloalkenyl group in the definition of G includes a C C linear or branched haloalk

twenty four

Examples of the kale group include a 2-cloethyl ether group, a 2-bromoethyl group, and a 2,2-dichloro ether group.

The alkoxy group in the definition of G is a C C linear or branched alkenyl group.

twenty four

Examples of the -loxy group include allyloxy group, 2-propenyloxy group, 2-butenyloxy group, 2-methyl 2-propyloxy group and the like.

As the haloalkoxy group in the definition of G, 3 chloro-2-propyloxy group, 3, 3 dichroic 2 propeloxy group, 4 chloro-2 butyroxy group, 4, 4-dichloro tertuloxy group, 4, 4 -Difluoro-3-butyroxy group and the like.

[0017] The alkenylsulfur group in the definition of G or Z is a C—C straight chain or

2 4 Branched alkylsulfur groups include arylsulfuryl group, 2-propylsulfuryl group, 2-butenylsulfuryl group, 2-methyl-2-propylsulfuryl group, etc. Can be mentioned.

The alkarylsulfier group in the definition of G or Z includes a C—C straight chain or

2 4 Examples of branched alkenylsulfuric groups include arylylsulfuric groups, 2-propylsulfuric groups, 2-butenylsulfuric groups, and 2-methyl-2-propylsulfuric groups. Can be mentioned.

The alkaryl sulfonyl group in the definition of G or Z includes C—C linear or branched

twenty four

Examples of the branched alkenylsulfol group include an arylsulfol group, a 2-probesulfol group, a 2-butenylsulfol group, and a 2-methyl-2-probesulfol group.

[0018] As the haloalkenylsulfur group in the definition of G, C—C linear or branched

twenty four

As a haloalkenylsulfuric group, a 3-chloro double-sulfur group , 4 Chloro 2 -Probenolenophenol group, 3,3 Dichloro 1 -Probenolenophenol group, 4, 4 -Dichloro-3 -butenylsulfur group, 4, 4 -Difluoro 3 —Butulsulfuryl group and the like can be mentioned.

As the haloalkenylsulfier group in the definition of G, C—C linear or branched

twenty four

As a haloalkenylsulfuric group in the form of 3-chloro opening, 2-propylsulfuryl group, 3,3 dichloro-2-probesulfuryl group, 3,3 dichloro-2-propylsulfuryl group, 4-chloro-2 group Examples thereof include a tenenyl sulfiel group, a 4,4-dichloro-3-butenyl sulfyl group, and a 4,4-difluoro-3-butenyl sulfiel group.

As the haloalkenyl group in the definition of G, C C linear or branched

twenty four

As the haloanoreke-noresnorehoninole group, there are three groups of 2-probenolesnorehoninole group, 3,3-dichloro-2 propeninoresnorehoninole group, 4 chloro-2-butenoresnorehoninole group Group, 4,4-dichloro-3-butenylsulfonyl group, 4,4-difluoro-3-butenylsulfonyl group and the like.

The C—C haloalkyl group in the definition of G includes a chloroethyl group and a bromoethyl group.

twenty four

-Lole group, odoethyl group, 3-chloro-1-propyl group, 3-bromo-1-butyl group and the like.

C—C alkyloxy group in the definition of G includes 2-propyloxy group, 2

twenty four

-Butynyloxy group, 1-methyl-2-propyloxy group and the like.

The C—C haloalkyloxy group in the definition of G includes 3

twenty four

-Luoxy group, 3 bromo-2 propyloxy group, 3 chloropropoxy group and the like.

The C—C alkynylsulfuric group in the definition of G is 2-propynylsulfuric

2 6

Examples thereof include a ethyl group, a 2-butylsulfuryl group, and a 1-methyl-2-propynylsulfuric group.

The C—C alkynylsulfier group in the definition of G includes 2-propynylsulfur

2 6

Examples thereof include a ethyl group, a 2-butylsulfier group, and a 1-methyl-2-propynylsulfier group. The C—C alkynylsulfol group in the definition of G is 2-propynylsulfo

2 6

Nyl group, 2-butylsulfol group, 1-methyl-2-propynylsulfol group and the like.

The C—C haloalkynylsulfuric group in the definition of G includes 3

2 6

Examples thereof include propyninoresnophenol group, 3 bromo-2 propyninoresphenol ether group, 3 chloro-2-propylsulfuryl group and the like.

As the C—C haloalkynyl sulfiel group in the definition of G, 3

2 6

Examples thereof include propyninores norefinino group, 3 bromo 2 propynino resno refinino group, 3 odo-2 propynyl sulfier group and the like.

The C—C haloalkynylsulfol group in the definition of G includes 3

2 6

Examples thereof include an oral pinolenoreno-nole group, a 3 bromo-2-propenorenorehoninole group, and a 3-iodo-2-propylsulfol group.

The benzoyl group which may be substituted with Z in the definition of G includes a benzoyl group, a 2-capped benzoyl group, a 3-capped benzoyl group, a 4-capped benzoyl group, a 4-bromobenzoyl group, and a 4-fullyl. Examples thereof include o-benzoyl group, 3-methylbenzoyl group, 4-methylbenzoyl group, 4-tertiarybutylbenzoyl group, and 3,4-dichlorobenzoyl group.

The phenyl group which may be substituted with Z in the definition of G includes a phenyl group, a 2-methylphenol group, a 3-methylphenol group, a 4-methylphenol group, and a 2-chlorophenol. Groups, 3-black mouth group, 4-black mouth group, 4-bromophenol group, 4-fluorophenyl group, 4 tertiary butyl phenol group, 3, 4-dichlorine mouth Examples include a phenol group.

Examples of the phenoxy group which may be substituted with Z in the definition of G include phenoxy group, 2-methylphenoxy group, 3-methylphenoxy group, 4-methylphenoxy group, 2-chlorophenoxy group, 3-chlorophenoxy group, 4-chlorophenoxy group. 4-bromophenoxy group, 4-fluorophenoxy group, 4-tertiarybutyl phenoxy group, 3,4-dichlorophenoxy group, and the like.

In the present invention, the organic solvent immiscible with water is benzene, toluene, xylene, Aromatic hydrocarbons such as ethylbenzene, aliphatic hydrocarbons such as hexane and heptane, and halogenated hydrocarbons such as chloromethylene and 1,2-dichloroethane, preferably aromatic hydrocarbons or aliphatic hydrocarbons Industrially more preferred is toluene or heptane.

[0020] Examples of the phase transfer catalyst include tetramethyl ammonium chloride, tetramethyl ammonium chloride, tetramethyl ammonium chloride, hydroxymethyl tetramethyl ammonium, tetraethyl ammonium chloride, tetraethyl ammonium chloride, tetraethyl ammonium chloride, Tetraethylammonium chloride, tetraethylammonium hydroxide, tetraptylammonium chloride, tetrabutylammonium bromide, tetraptylammonium chloride, tetrabutylammonium hydroxide, trimethylbenzylammonium chloride, trimethylbenzylammumum Mouth amide, trimethylbenzylammozide, trimethylbenzylammohydrate, trietenoleveninoleumumum chloride, trietinolevenorenum momum Ethylbenzylammozide, Triethylbenzylammonium hydroxide, Triethylmethylammonium chloride, Triethylmethylammonium bromide, Triethylmethylammonium chloride, Triethylmethylammonium hydroxide, Trimethyl Ethylammochloride, trimethylethylmombromide, trimethylethylmolybdenum, trimethylethylammonium hydroxide, methyltributylammonium chloride, methyltributylammonium bromide, methyltributylammonium chloride, Methyltributylammonium hydroxide, methyltrioctylammonium chloride, methyltrioctylammonium bromide, methyltrioctylammonium chloride, hydroxy-methyltrioctylammonium , A quaternary ammonium salt such as tetramethylammonium acetate, preferably tetraalkylammonium halide such as tetraptylamumumumide, and more preferably tetrabutylammonium bromide in view of price. It is.

[0021] The amount of the phase transfer catalyst used is preferably from 0.01 to 0.5 equivalent to the raw material halomethylthiazole, more preferably from 0.05 to 0.2 equivalent.

The reaction temperature is preferably 30 ° C or higher and 150 ° C or lower, more preferably 50 ° C or higher and 100 ° C or lower. The amount of the organic solvent used is preferably 1 to 20 parts by weight, more preferably 3 to 10 parts by weight, based on the raw material halomethylthiazole.

The amount of metal cyanide such as sodium cyanide and potassium cyanide used is preferably 0.9 to 1.5 equivalents relative to the raw material halomethylthiazole, more preferably 1.0 to 1.1.

The amount of water used in the reaction is preferably 0.5 to 5 parts by weight based on the raw material halomethylthiazole! /, But is preferably 1 to 3 parts by weight.

The reaction is preferably carried out in an atmosphere of an inert gas such as nitrogen or argon, but industrially, nitrogen is preferred because it is inexpensive.

In the present invention, reaction reagents may be charged all at once, and the temperature may be raised. However, a method such as dropwise addition of an aqueous solution of a phase transfer catalyst and an alkali metal cyanide to an organic solvent or water mixture of heated halomethylthiazole while maintaining the temperature Is also effective.

In the present invention, after the reaction, the aqueous layer is separated and subjected to normal treatment. However, the product can be used in the next step as it is without isolating the product from the organic layer, which is industrially more advantageous. .

Example

EXAMPLES Hereinafter, the present invention will be specifically described with reference to examples, but the present invention is not limited thereto.

Example 1

2-Ferreux 4-Chloromethylthiazole 1. 05 g (5 mmol), toluene 5.25 g (5 parts by weight), cyanobium sodium 0.27 g (5.5 mmol) and water 1.05 g (l parts by weight) ) Was mixed with a mixture of tetraptylammonum bromide 0.32 g (l mmol) at 60 ° C. and reacted for 6 hours. After completion of the reaction, ethyl acetate was added to separate the aqueous layer. Quantitative analysis of the organic layer using high-performance liquid chromatography confirmed the production of 0.95 g of 2-phenyl-4-cyanomethylthiazole (yield 95%).

Example 2

2-Fue-Lou 4-Chloromethylthiazole 1.05 g (5 mmol), heptane 10.5 g (10 parts by weight), cyanobium sodium 0.27 g (5.5 mmol) and water 1.05 g (l part by weight) Mix of A mixture of tetraptyl ammonium bromide (0.16 g, 0.5 mmol) was heated to 50 ° C. and reacted for 6 hours. After completion of the reaction, ethyl acetate was added to separate the aqueous layer. Quantitative analysis of the organic layer using high-speed liquid chromatography confirmed the formation of 0.97 g of 2-ferro-4-cyanomethyl thiazole (yield 96.8%).

Industrial applicability

The present invention is useful as an efficient method for producing a thiazole-substituted acetonitrile compound useful as an intermediate for producing agricultural medicine.

Claims

Claim [1] Formula (1)

[Chemical 1]

Q— CH ₂ X (1)

[Wherein Q is substituted with G and may be a thiazolyl group;

X is a halogen atom,

G is a halogen atom, a C 1 -C alkyl group, a C C cyanoalkyl group, or a halogen atom.

1 10 2 4

1 4 1 4 alkyl group, C—C alkenyl group, C C alkynyl group, C—C haloalkyl group, C

2 5 2 6 1 6 2

-C haloalkenyl group, C—C haloalkynyl group, C—C halocycloalkyl group, C

6 2 6 3 6

A -C cycloalkyl group optionally substituted with a -C alkyl group, c -c alkoxy

1 3 3 6 1 10 Si group, C-C alkenyloxy group, C C alkynyloxy group, C C haloalkoxy

2 6 2 6 1 4 Xoxy group, C—C haloalkenyloxy group, C—C haloalkyloxy group, C—C

2 6 2 6 1 4 Alkylsulfenyl group, C—C alkylsulfinyl group, C—C alkylsulfonyl group

1 4 1 4

Group, C-C alkenylsulfinyl group, C-C alkenylsulfinyl group, C-C

2 6 2 6 2 Alkenylsulfonyl group, C—C alkynylsulfenyl group, C—C anolenoquinoles

6 2 6 2 6

Rufel group, C C alkynylsulfonyl group, c C /, Alkylsulfenyl

2 6 1 4

Group, C—C haloalkylsulfier group, C—C haloalkylsulfonyl group, C—C

1 4 1 4 2 Noroanorekeninolesnore fenenore group, C C Nooanorekeninoresno refininore group, C—C Noro

6 2 6 2 6 Anolekeninores norehoninore group, c -c Noanorequininores norewere / re group, c -c Nonoanore

2 6 2 6 Quinylsulfiel group, C 2 -C haloalkynylsulfonyl group, CHO, NO, CN, O

2 6 2

H, naphthyl group, halogen atom or C-C alkyl group may be substituted.

1

A methoxy group substituted with an phenyl group, a c-C alkoxycarbonyl group,

2 5 C 2 C Alky

4 Sialkyl group, C C alkylcarbonyl group, C C haloalkylcarbonyl group,

2 4 2 4

C C alkylcarbonyloxy group, C C haloalkylcarbonyloxy group, C

2 5 2 5 3

-C dialkylaminocarbonyloxy group, phenyl group optionally substituted by Z, Z

7 A phenoxy group which may be substituted with Z, a benzoyl group which may be substituted with Z, a pyridyl group which may be substituted with Z, a pyridyloxy group which may be substituted with Z, However, a ring group, a methylenedioxy group bonded at an adjacent substitution position, a bonded halomethylenedioxy group bonded at an adjacent substitution position, and —N = CT′T ² (where T ¹ and T ² Each independently represents H, a phenyl group, a benzyl group or a C—C alkyl group.

It may form a 5-membered ring, a 6-membered ring, a 7-membered ring or an 8-membered ring with the carbon atom to which the forces T ¹ and T ² which are 16 groups are bonded. ) Is a substituent arbitrarily selected from the above (provided that when there are two or more substituents, they may be the same or different from each other), and the number of the substituents is one or two. A 5-membered ring, a 6-membered ring, a 7-membered ring or an 8-membered ring formed by an alkylene group bonded to each other at adjacent substitution positions;

Z is a halogen atom, C—C alkyl group, C—C haloalkyl group, C—C alkoxy

1 4 1 4 1 4

Rufyl group, C—C alkylsulfol group, C—C alkylsulfur group, C

1 4 2 5 2

— C-alkulsulfyl group, C— C-alkylsulfol group, C—C haloal group

5 2 5 1 4 Kill sulfo group, NO, CN, CHO, OH, -NU ^J U ² , phenol group, phenoxy group

2

Or C—C alkoxycarbo group medium force Arbitrarily selected substituents (however,

twenty five

When there are two or more substituents, they may be different from each other with the same force. ) And the number of substituents is 1, 2, 3, 4 or 5,

U ¹ and U ² are each independently H, C—C alkyl group, C—C alkyl carbo-

1 6 2 5

Formula (2)

[Chemical 2]

Q—CH CN (2) (Wherein Q represents the same meaning as described above), and a method for producing a thiazole-substituted acetonitrile compound.

[2] The method for producing a thiazole-substituted acetonitrile compound represented by the formula (2) according to claim 1, wherein the Q is a 2-phenylthiazole-4-yl group.

[3] The method for producing a thiazole-substituted acetonitrile compound represented by the formula (2) according to [1], wherein the phase transfer catalyst is tetraptyl ammonium halide and the reaction solvent is toluene or heptane.

[4] The formula (2) according to claim 1, wherein the Q is a 2-phenylthiazol-4-yl group, the phase transfer catalyst is tetrabutylammonum halide, and the reaction solvent is toluene or heptane. A method for producing a thiazole substituted acetonitrile compound.