JPH059173A - Production of guanidine derivative, its intermediate thereof and production thereof - Google Patents

Abstract

PURPOSE:To provide compounds useful as an intermediate for synthesis of an insecticide and a mitecide. CONSTITUTION:Compounds of formula I(R is hydrocarbon or acyl; X is electron- attracting group; Y<1> and Y<2> are O or S; A is divalent hydrocarbon), e.g. S- methyl-N-nitro-N-phthaloylisothiourea. The compounds of formula I can be obtained by reacting a compound of formula II with a compound of formula III (Z<1> and Z<2> are halogen, or Z<1> and Z<2> together form O) preferably in the presence of a base (e.g. potassium hydroxide) in a solvent (e.g. acetonitrile) at -50-200 deg.C. The compounds of formula I can be converted into the corresponding quanidine derivatives by reaction with an amine, followed by reaction with a compound of formula R<3>-NH(CH2)n-B (B is homocycle or heterocycle which may be substituted; (n) is 0 or 1; R<3> is H or hydrocarbon).

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a method for producing a guanidine derivative, an intermediate for synthesizing the guanidine derivative, and a method for producing the intermediate. The guanidine derivative is useful as an insecticide and acaricide (Japanese Patent Application No. 1-333372).
No. 1).

[0002]

2. Description of the Related Art Conventionally, N-substituted-N'-nitroisothiourea derivatives and N-monocyclic (methyl) -N'-nitroisothiourea derivatives, which are useful as synthetic intermediates for guanidine derivatives, have been synthesized by the following methods. A method of nitration with sulfuric acid-fuming nitric acid is known [Journal of American Chemical Society (J
individual of American Chemical
al Society), Vol. 76, p. 1877 (1
954)]. However, according to this method, the nitration of isothioureas having an alkyl substituent at the nitrogen atom has a very low yield, and is not satisfactory as a general synthetic method or an industrial production method.

[0003]

In view of the above-mentioned circumstances, the present invention is a technique which can be industrially implemented economically with good yield, and N, which is useful as a synthetic intermediate of a guanidine derivative,
In addition to finding a novel synthetic intermediate for producing an N′-di-substituted isothiourea derivative and an N-cyclic (methyl) -N′-substituted isothiourea derivative, a process for producing the same and an insecticide using the intermediate, It is an object of the present invention to provide a method for producing a novel guanidine derivative which is extremely useful as an acaricide.

[0004]

[Means for Solving the Problems] The inventors of the present invention have diligently studied to solve the above problems, and as a result,

[Chemical 18] [Wherein R is an optionally substituted hydrocarbon group or an acyl group, X is an electron withdrawing group, Y ¹ and Y ² are the same or different and are oxygen or sulfur, and A is optionally substituted. It shows a good divalent hydrocarbon group. The present invention has been completed by discovering that the compound represented by the formula [] is surprisingly highly reactive, and that the cyclic di (thio) acylimide moiety first undergoes a substitution reaction by the amines, and then the RS moiety undergoes a substitution reaction. That is,
The present invention is

(1) A compound of the formula [1],

Equation (2)

[Chemical 19] [In the formula, R and X have the same meanings as described above. ] And a compound represented by

[Chemical 20] [Wherein A, Y ¹ and Y ² have the same meanings as described above, Z ¹ , Z
^2's are the same or different and represent halogen or, together, represent oxygen. ] The compound of the formula [I] characterized by reacting with the compound of the formula

(3) The compound represented by the formula [I] and the formula R ¹ R ² NH [IV] [wherein, R ¹ and R ² are the same or different and are hydrogen or an optionally substituted hydrocarbon group. Or together represent a cyclic amino group with the adjacent nitrogen. ] Reacting with amines or salts thereof represented by the formula:

[Chemical 21] [The symbols in the formula have the same meanings as described above. ] The manufacturing method of the compound or its salt represented by these,

(4) When R ¹ represents a hydrogen atom, the compound represented by the formula [V] obtained by the production method of the above (3) or a salt thereof is optionally acylated, and then the compound represented by the formula R ³ -NH (CH 2) _n-B (VI) wherein, B is a homo- optionally substituted or a heterocyclic group, n represents 0 or 1, R ³ may be hydrogen or substituted Indicates a hydrocarbon group. ] The compound or its salt represented by these are represented, The formula characterized by the above-mentioned.

[Chemical formula 22] [In the formula, R ^1a represents a hydrogen atom, an optionally substituted hydrocarbon group or an acyl group, and other symbols have the same meanings as described above. ] The manufacturing method of the compound or its salt represented by these,

(5) A compound represented by the formula [I] and a compound represented by the formula R ³ —NH (CH ₂ ) nB [VI] [wherein each symbol has the same meaning as defined above]. ] The compound or its salt represented by these are represented, The formula characterized by the above-mentioned.

[Chemical formula 23] [The symbols in the formula have the same meanings as described above. ] The manufacturing method of the compound or its salt represented by these,

(6) When R ³ represents a hydrogen atom, the compound [VII] or a salt thereof obtained by the production method of the above item (5) is optionally acylated, and then the compound of the formula R ¹ R ² NH [IV] [The symbols in the formula have the same meanings as described above. ] Reacting with amines or salts thereof represented by the formula:

[Chemical formula 24] [In the formula, R ^3a represents a hydrogen atom, an optionally substituted hydrocarbon group or an acyl group, and other symbols have the same meanings as described above. ] It is related with the manufacturing method of the compound represented by these, or its salt.

In the above formula, the optionally substituted hydrocarbon group or acyl group of R is, for example, an optionally substituted C _1-10 alkyl group or an optionally substituted C group.
_2-10 alkenyl group, _optionally substituted C
_2-10 alkynyl group, _optionally substituted C
_7-12 aralkyl group, _optionally substituted C
_{1-10 represents} an acyl group or the like. Examples of the C _1-10 alkyl group represented by R include methyl, ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl, n-
Linear alkyl groups such as heptyl, n-octyl, n-decyl, i-propyl, i-butyl, s-butyl, t-butyl, i-pentyl, s-pentyl, t-pentyl, i-
A branched alkyl group such as hexyl, s-hexyl and t-hexyl, and a cyclic alkyl group such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl are used. Examples of the C _2-10 alkenyl group represented by R include vinyl, allyl, 2-butenyl, 1-pentenyl and the like. As the C _2-10 alkynyl group represented by R, for example, 1-ethynyl, propargyl, 2-butynyl, 1-pentynyl group and the like are used. Examples of the C _1-10 acyl group represented by R include straight-chain C _1-10 acyl such as formyl, acetyl, and propionyl, and methylene at the terminal end on the bond side of the alkyl group described above as the C _1-10 alkyl group. An acyl group or the like obtained by substituting the group with a carbonyl group is used. _{Examples of} the C _7-12 aralkyl group represented by R include benzyl, 1-phenethyl, 2-phenethyl and 1
-Naphthylmethyl, 2-naphthylmethyl and the like are used. C _1-10 alkyl group represented by R, C
_2-10 alkenyl group, C _2-10 alkynyl group, C
_{The 1-10} acyl group or C _7-12 aralkyl group may have 1 to 5 identical or different substituents,
Examples of such a substituent include a cycloalkyl group having 3 to 10 carbon atoms such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, etc., such as vinyl, allyl, 2-methylallyl, 2-butenyl, 3-butenyl,
Alkenyl groups having 2 to 10 carbon atoms such as 3-octenyl, for example, alkynyl groups having 2 to 10 carbon atoms such as ethynyl, 2-propynyl, and 3-hexynyl, and 3 to 10 carbon atoms such as cyclopropenyl, cyclopentenyl, and cyclohexenyl. 10 cycloalkenyl groups, nitro, hydroxyl group, mercapto, oxo, thioxo, cyano, carbamoyl, carboxyl, C _1-4 alkoxycarbonyl such as methoxycarbonyl and ethoxycarbonyl, sulfo, such as fluorine, chlorine, bromine and iodine. Halogen, such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, s-butoxy, t
- _{C 1-4} alkoxy butoxy, e.g. _{C 6-10} aryloxy such as phenoxy, such as methylthio, ethylthio, n- propylthio, isopropylthio, n- butylthio, _{C 1-4} alkylthio such as t- butylthio, for example phenylthio _{C 6-10} arylthio etc., for example, methylsulfinyl, _{C 1-4} alkylsulfinyl such as ethylsulfinyl, for example _{C 6-10} arylsulfinyl, such as methyl sulfonyl, such as phenylsulfinyl, _{C 1-4} alkylsulfonyl such as ethylsulfonyl, C _6-10 arylsulfonyl such as phenylsulfonyl, amino, C _2-6 such as acetylamino, propionylamino and the like.
Acylamino, such as methylamino, ethylamino,
Mono- or di-C _1-4 alkylamino such as n-propylamino, isopropylamino, n-butylamino, dimethylamino, cyethylamino, C _3-6 cycloalkylamino such as cyclohexylamino, C ₆ such as anilino, etc. _-10 arylamino, eg C _2-4 acyl such as acetyl, eg C such as benzoyl
_6-10 aryl-carbonyl, such as 2- or 3
-Thienyl, 2- or 3-furyl, 3-, 4- or 5-pyrazolyl, 2-, 4- or 5-thiazolyl, 3
-, 4- or 5-isothiazolyl, 2-, 4- or 5-oxazolyl, 3-, 4- or 5-isoxazolyl, 2-, 4- or 5-imidazolyl, 1, 2, 3
-Or 1,2,4-triazolyl, 1H or 2H-
Tetrazolyl, 2-, 3- or 4-pyridyl, 2-,
Oxygen such as 4- or 5-pyrimidinyl, 3- or 4-pyridazinyl, quinolyl, isoquinolyl and indolyl,
5 to 1 containing 4 heteroatoms selected from sulfur and nitrogen
A 6-membered heterocyclic group or the like is used, and R is an optionally substituted C _7-12 aralkyl group or an optionally substituted C.
_When it is a _1-10 acyl group, for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, s-butyl, t-butyl, pentyl, hexyl,
C1-C15 alkyl groups such as heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, etc., such as phenyl, naphthyl, and other C6-10 aryl groups, such as benzyl, phenylethyl, etc. An aralkyl group having 7 to 10 carbon atoms is used as a substituent. These substituents are, for example, C _6-10 aryl, C _7-10 aralkyl, C
_3-10 cycloalkyl, C _3-10 cycloalkenyl, C _6-10 aryloxy, C _6-10 arylthio, C _6-10 arylsulfinyl, C _6-10 arylsulfonyl, C _6-10 arylamino, heterocyclic group And the like, further halogen, hydroxyl group such as C _1-4 alkyl such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, s-butyl, t-butyl, etc., such as vinyl, allyl, 2- C _2-4 alkenyl such as methylallyl, eg ethynyl,
C _2-4 alkynyl such as 2-propynyl, C _6-10 aryl as described above, C _1-4 alkoxy as described above, phenoxy, C _1-4 alkylthio as described above,
It may be substituted with 1 to 5 phenylthio and the like, and the substituent is C _1-15 alkyl, C _2-10 alkenyl,
C _2-10 alkynyl, C _1-4 alkoxy, C _1-4
Alkylthio, C _1-4 alkylsulfinyl, C
_1-4 alkylsulfonyl, amino, mono- or di-C
_{When it is 1-4} alkylamino, C _3-6 cycloalkylamino, C _6-10 arylamino, etc., it further includes the above-mentioned halogen, hydroxyl group, C _1-4 alkoxy such as methoxy, ethoxy, etc., methylthio, ethylthio, etc. C
₁ to 5 substituents such as _1-4 alkylthio may be substituted.

Preferred examples of R are C _1-4 alkyl groups such as methyl and ethyl, or C such as benzyl.
_{It is a 7-10} aralkyl group.

In the above formula, the optionally substituted divalent hydrocarbon group of A is, for example, an optionally substituted divalent saturated or unsaturated chain hydrocarbon group having 1 to 4 carbon atoms. Or a divalent saturated or unsaturated cyclic hydrocarbon group having 3 to 8 carbon atoms which may be substituted.

Examples of the chain hydrocarbon group include "optionally substituted divalent C _1-4 alkylene or C
" _2-4 alkenylene group" and the like are examples of the cyclic hydrocarbon group such as "formula

[Chemical 25] [In the formula, the ring C represents an optionally substituted saturated or unsaturated C _3-8 cyclic hydrocarbon, and m represents 0 or 1. ] The group represented by], etc.

Examples of the C ring are, for example, "optionally substituted benzene ring or C _3-8 cycloalkane, C
_3-8 cycloalkene "and the like.

[0016] As the divalent _{C 1-4} alkylene group "substituted 2 may be divalent _{C 1-4} alkylene group",
For example,

[Chemical formula 26] Etc. are used. “Divalent C that may be substituted
Examples of the divalent C _2-4 alkenylene group of “ _2-4 alkenylene group” include:

[Chemical 27] Etc. are used.

In addition, "optionally substituted C" of the C ring
_3-8 cycloalkane, C _3-8 cycloalkene "
_{As the 3-8} cycloalkane and C _3-8 cycloalkene, for example, cyclopropane, cyclobutane, cyclopentane, cyclohexane, cycloheptane, cyclooctane, cyclopentene, cyclohexene and the like are used.

The chain hydrocarbon group or cyclic hydrocarbon group represented by A may have 1 to 5 substituents. Examples of such a substituent include halogen such as fluorine atom, chlorine atom, bromine atom and iodine atom, for example, methyl, ethyl, n-propyl, i-propyl, n-butyl, s-butyl, t-butyl and the like. An alkyl group having 1 to 4 carbon atoms, for example, an alkoxy group having 1 to 4 carbon atoms such as methoxy, ethoxy, n-propoxy, n-butoxy, t-butoxy, etc., having 1 to 5 carbon atoms such as acetoxy and propionyloxy. Acyloxy group, for example, methoxycarbonyloxy, ethoxycarbonyloxy, and other C2-5 alkoxycarbonyloxy groups, such as methylthio, ethylthio, i-butylthio, t-butylthio, and other alkylthio groups, such as methylsulfinyl , Ethylsulfinyl, n-propylsulfinyl, i-butyls Carbon atoms such as Finiru 1-4
An alkylsulfinyl group of, for example, methylsulfonyl,
An alkylsulfonyl group having 1 to 4 carbon atoms such as ethylsulfonyl, i-butylsulfonyl and n-butylsulfonyl, and an aralkylthio group having 7 to 12 carbon atoms such as benzylthio and naphthylmethylthio are used.

Preferred examples of A include a phenylene group such as o-phenylene and a C _2-4 alkylene group such as 1,2-ethylene and 1,3-propylene.

In the above formula, Y ¹ and Y ² are the same or different and each represents an oxygen atom or a sulfur atom. A preferred example of Y ¹ and Y ² is an oxygen atom.

In the above formula, the electron withdrawing group represented by X is, for example, cyano, nitro, alkoxycarbonyl (for example, C _1-4 alkoxy-carbonyl such as methoxycarbonyl or ethoxycarbonyl), hydroxycarbonyl, C _6-10. Aryl-oxycarbonyl (eg phenoxycarbonyl etc.), heterocyclic oxycarbonyl (heterocyclic groups such as those mentioned above are used, eg pyridyloxycarbonyl, thienyloxycarbonyl etc.), eg halogen (Cl, Br etc.) etc. Optionally substituted C _1-4 alkylsulfonyl (eg methylsulfonyl, trifluoromethylsulfonyl,
Ethylsulfonyl etc.), sulfamoyl, di-C _1-4
Alkoxyphosphoryl (eg diethoxyphosphoryl etc.), C _1-4 acyl optionally substituted by halogen (Cl, Br etc.) etc. (eg acetyl, trichloroacetyl, trifluoroacetyl etc.), carbamoyl, C _1-4. Alkylsulfonylthiocarbamoyl (eg, methylsulfonylthiocarbamoyl etc.) and the like are used. Preferred electron withdrawing groups are, for example, nitro and the like.

In the above formula, Z ¹ and Z ² are the same or different and each represents a halogen atom such as a fluorine atom, a chlorine atom or a bromine atom, or together represents an oxygen atom.

A preferred example of Z ¹ and Z ² is halogen such as chlorine atom.

In the above formula, the hydrocarbon group of the “optionally substituted hydrocarbon group” represented by R ¹ , R ² , R ³ , R ^1a and R ^3a is, for example, the one as described above for R. (In particular, a C _1-10 alkyl group, a C _2-10 alkenyl group, and a C _2-10 alkynyl group, which are linear,
Those that may be branched or annular are commonly used. ) And the like are used. Further, as the substituent of the “hydrocarbon group which may be substituted”, those mentioned as the substituent in the above description of R and the like can be used. Examples of the cyclic amino group represented by R ¹ and R ² together with the adjacent nitrogen include aziridino, azetidino, pyrrolidino, morpholino and thiomorpholino groups.
The acyl group represented by R ^1a and R ^3a is, for example, the above R
In the above description, those mentioned as the acyl group are used.

R ¹ and R ² , or R ^1a and R ²
Preferred examples of R ¹ R ² N or R ^1a R ² N consisting of a nitrogen atom and an adjacent nitrogen atom include, for example, an unsubstituted amino group, for example, mono-C such as methylamino, ethylamino or propylamino.
_{A 1-4} alkylamino group, for example, a di-C _1-4 alkylamino group such as dimethylamino or ethylmethylamino is used, and R ^1a R ² N is an acylamino group such as a formylamino group or an acetylamino group. Also preferred are N-C _1-2 acyl-N-C _1-4 alkylamino groups such as N, N-formyl-N-methylamiso group and N-acetyl-N-methylamino group. Preferred examples of R ³ and R ^3a are, for example, hydrogen, for example, C _1-4 alkyl groups such as methyl, ethyl, propyl, etc., and for R ^3a , formyl group and acetyl group are also preferred.

In the above formula, B represents an optionally substituted homologous or heterocyclic group. The homologous or heterocyclic group represented by B is a cyclic group containing only the same atom or a cyclic group containing two or more different atoms, and means a cyclic hydrocarbon group or a heterocyclic group. Examples of the cyclic hydrocarbon group represented by B include cyclopropyl, cyclobutyl,
Cyclopentyl, _{C 3-8} cycloalkyl groups such as cyclohexyl, for example Shikuropurobeniru, 1-cyclopentenyl, 1-cyclohexenyl, 2-cyclohexenyl, 1,3-cyclohexadienyl _{C 3-8} cycloalkenyl group enyl and the like, such as phenyl , 1- or 2-naphthyl, 1-, 2- or 9-anthryl, 1-, 2-,
3-, 4- or 9-phenanthryl, 1-, 2-, 4
A C _6-14 aryl group such as 1,5- or 6-azulenyl is used. Preferred cyclic hydrocarbon groups are, for example, aromatic ones, such as C _6-14 aryl groups such as phenyl. As the heterocyclic group represented by B, for example, a hetero atom such as an oxygen atom, a sulfur atom, or a nitrogen atom is 1
A 5- to 8-membered ring group containing 5 to 5 or a condensed ring group thereof is used, and specific examples thereof include 2- or 3-thienyl, 2- or 3-furyl, 2- or 3-pyrrolyl, 2- , 3- or 4-pyridyl, 2-, 4- or 5-oxazolyl, 2-, 4- or 5-thiazolyl,
3-, 4- or 5-pyrazolyl, 2-, 4- or 5
-Imidazolyl, 3-, 4- or 5-isoxazolyl, 3-, 4- or 5-isothiazolyl, 3- or 5- (1,2,4-oxadiazolyl), 1,3,4-
Oxadiazolyl, 3- or 5- (1,2,4-thiadiazolyl), 1,3,4-thiadiazolyl, 4- or 5- (1,2,3-thiadiazolyl), 1,2,5-
Thiadiazolyl, 1,2,3-triazolyl, 1,2,
4-triazolyl, 1H- or 2H-tetrazolyl,
N-oxide-2-, 3- or 4-pyridyl, 2-,
4- or 5-pyrimidinyl, N-oxide-2-, 4
-Or 5-pyrimidinyl, 3- or 4-pyridazinyl, pyrazinyl, N-oxide-2- or 3-pyrazinyl, N-oxide-3- or 4-pyridazinyl, benzofuryl, benzothienyl, benzothiazolyl, benzoxazolyl, triazinyl, Oxotriazinyl,
Tetrazolo [1,5-b] pyridazinyl, triazolo [4,5-b] pyridazinyl, oxoimidazolyl, dioxotriazinyl, pyrrolidinyl, piperidinyl, pyranyl, thiopyranyl, 1,4-oxazinyl, morpholinyl, 1,4-thiazinyl , 1,3-thiazinyl, piberazinyl, benzimidazolyl, quinolyl, isoquinolyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, indolizinyl, quinolidinyl, 1,8
-Naphthyridinyl, purinyl, pteridinyl, dibenzofuranyl, carbazolyl, acridinyl, phenanthridinyl, phenazinyl, phenothiazinyl, phenoxazinyl and the like are used. The preferred heterocyclic group is
For example, it is a 5- or 6-membered nitrogen-containing heterocyclic group such as 2-, 3- or 4-pyridyl, 2-, 4- or 5-thiazolyl. The homologous or heterocyclic group represented by B may have 1 to 5 (preferably 1) the same or different substituents, and such a substituent is, for example, the one described in R above. The same thing is used.

A preferred example of B is, for example, 1 for halogen.
Or a 5- or 6-membered nitrogen-containing heterocyclic group such as pyridyl or thiazolyl which may be substituted with two or the like.

The starting material compound (II) of the present invention can be used, for example, in the Journal of American Chemistry (Journal of American Chem).
Icial Society), Vol. 76, Page 1877 (1954) and the like, or a method similar thereto.

The reaction for converting the compound [II] into the compound [I] of the present invention can be achieved by reacting the compound [II] with the compound [III]. This reaction can be carried out using a suitable solvent. The solvent is not particularly limited as long as it does not react with the reaction substrate, the reaction reagent and the product to give a by-product, but a solvent that dissolves both the reaction substrate and the reaction reagent is preferable. Such solvents include benzene, toluene, aromatic hydrocarbons such as xylene, methyl acetate, ethyl acetate, ethyl formate, esters such as ethyl propionate, acetone, ketones such as methyl ethyl ketone, diethyl ether, dipropyl ether, Ethers such as dibutyl ether, tetrahydrofuran, dioxane, nitriles such as acetonitrile and propionitrile, acid amides such as dimethylformamide and dimethylacetamide, sulfoxides such as dimethyl sulfoxide, sulfones such as sulfolane, and hexamethylphosphole. Phosphoramides such as amides, dichloromethane, chloroform, 1,2-dichloroethane, halogenated hydrocarbons such as carbon tetrachloride, aromatic amines such as pyridine, picoline, lutidine, quinoline, and mixtures thereof. Solvent, further a mixed solvent of these with water is used. Of these, pyridine, α-picoline, pyridines such as 2,6-lutidine, nitriles such as acetonitrile, and halogenated hydrocarbons such as chloroform and dichloromethane are particularly preferable.

For the purpose of promoting the reaction and reducing the amount of by-products, good results may be obtained by allowing a base to coexist or act before and after the reaction. Examples of the base in such a case include sodium hydride, sodium,
For example sodium ethylate, natrimethylate,
Alkali metal alcoholates such as potassium tert-butoxide, organic bases such as triethylamine, diisopropylethylamine, pyridine, N, N-dimethylaniline, such as potassium carbonate, sodium carbonate, sodium hydroxide, potassium hydroxide, sodium hydrogen carbonate,
An inorganic base such as potassium hydrogen carbonate can be used.
The amount of the base used is not particularly limited as long as it does not adversely affect the reaction, and a large excess amount can also be used as a solvent as in the case of pyridine, for example.

The amount of [III] used as a reaction reagent is 1 to 5 times, preferably 1 to 2.5 times, the molar amount of [II].

The temperature used in the reaction is usually -50 to 20.
It is 0 ° C., preferably −30 to 50 ° C. The reaction time is generally 0.1 to 24 hours, preferably 0.1 to 1
It's 0 hours. The obtained compound [I] is separated or purified by a means known per se, for example, concentration, reduced pressure concentration, liquid conversion, phase transfer, solvent extraction, distillation, crystallization, recrystallization, chromatography or the like, or a reaction mixture. It may be used as it is as a raw material for the next reaction.

The di (thio) carboxylic acid derivative [III] used in the above step is often a known compound, but if necessary, for example, “The Chemistry of Acid Derivatives Part 1 (The Ch
emissary of acid derivativ
es, Part 1) ”, JOHN WILEY & S
ONS (1979), Chapter 7, "The Chemistry of Acid Derivatives Part 2 (The c
hemistry of acidderivativ
es Part 2) ", JOHN WILEY &
Sons (1979), Chapter 11, or “The Chemistry of Acyll Horizon” (The Chemi)
“Stry of acyl halides)”, JO
The synthesis can be carried out by the method described in HNWILEY & SONS (1972), Chapter 2 or the like, or a method analogous thereto.

[I] → [V] and [I] → [VII]
Each reaction can be achieved by reacting [I] with an amine represented by [IV] or a salt thereof, or an amino cyclic compound represented by [VI] or a salt thereof.
This reaction can be carried out using a suitable solvent. The solvent is not particularly limited as long as it does not react with the reaction substrate, the reaction reagent, and the product to give a by-product, but a solvent that dissolves both the reaction substrate and the reaction reagent is preferable. Examples of such a solvent include aliphatic hydrocarbons such as pentane, hexane, heptane and petroleum ether, aromatic hydrocarbons such as benzene, toluene and xylene, esters such as methyl acetate, ethyl acetate, ethyl formate and ethyl propionate. , Ketones such as acetone and methyl ethyl ketone, ethers such as diethyl ether, dipropyl ether, dibutyl ether, tetrahydrofuran and dioxane, methanol, ethanol, propanol,
Alcohols such as butanol, acetonitrile, nitriles such as propionitrile, acid amides such as dimethylformamide and dimethylacetamide, sulfoxides such as dimethylsulfoxide, sulfones such as sulfolane,
Phosphoric acid amides such as hexamethylphosphoramide, dichloromethane, chloroform, 1,2-dichloroethane,
Halogenated hydrocarbons such as carbon tetrachloride, aromatic amines such as pyridine, picoline, lutidine, quinoline, mixed solvents thereof, and mixed solvents of these and water are used.

Compound (IV) used as a reaction reagent
The amount of the salt or the compound [VI] or the salt thereof may be 1 to 2 times the molar amount of the compound [I], but an excess amount of the compound (IV) or the salt thereof is bisamino. Since the body may be by-produced, it is preferable to use a molar amount of 1 to 1.3 times, The temperature used for the reaction is usually -50 to 100 ° C, preferably -30 to 50 ° C. The reaction time is generally 0.
It is 1 to 24 hours, preferably 0.1 to 10 hours. The obtained compound [V] or compound [VII] or a salt thereof is known per se, for example, concentration, concentration under reduced pressure, liquid conversion, solvent transfer, solvent extraction, distillation, crystallization, recrystallization, chromatography and the like. After separation and purification by, or the reaction mixture as it is may be used as a raw material for the next reaction.

The amines [I
V] or a salt thereof is, for example, “Survey of Organic Synthesis (Survey of Organic Synthesis)”.
icSyntheses) ”, Wiley-Inter
Science (1970), Chapter 8 and the like, or a method analogous thereto, and the amino cyclic compound [VI] or a salt thereof is, for example, "organic
Functional Group Preparations (O
electronic Functional Group Pr
) "Academic Pres
s, Volume 1, Chapter 13 (1968), Volume 3, Volume 1
It can be synthesized by the method described in Chapter 0 (1972) and JP-A-2-171 or the like or a method analogous thereto.

[V] → [VIII] and [VII] →
The respective reactions of (IX) are the same as those of compound [V] or [VII], in which R ¹ and R ³ each represent a hydrogen atom,
If necessary, it can be acylated and then reacted with (IV) or [VI] .Reaction reagents used in such an acylation reaction include known acids such as formic acid, formic acid acetic anhydride, and formylimidazole. Formylating agent,
Known acylating agents such as acetyl chloride and acetic anhydride are used.

This reaction can be carried out using a suitable solvent. The solvent is not particularly limited as long as it does not react with the reaction substrate, the reaction reagent and the product to give a by-product, but a solvent that dissolves both the reaction substrate and the reaction reagent is preferable. Such solvents include benzene, toluene, aromatic hydrocarbons such as xylene, methyl acetate, ethyl acetate, ethyl formate, esters such as ethyl propionate, acetone, ketones such as methyl ethyl ketone, diethyl ether, dipropyl ether, Ethers such as dibutyl ether, tetrahydrofuran, dioxane, nitriles such as acetonitrile and propionitrile, acid amides such as dimethylformamide and dimeracetamide, sulfoxides such as dimethyl sulfoxide, sulfones such as sulfolane, and hexamethylphosphor Phosphoramides such as amides, dichloromethane, chloroform, 1,2-dichloroethane, halogenated hydrocarbons such as carbon tetrachloride, aromatic amines such as pyridine, picoline, lutidine, quinoline, and mixtures thereof. Solvent,
Further, a mixed solvent of these and water is used. Of these, pyridine, α-picoline, pyridines such as 2,6-lutidine, nitriles such as acetonitrile, and halogenated hydrocarbons such as chloroform and dichloromethane are particularly preferable.

For the purpose of promoting the reaction and reducing the amount of by-products, good results may be obtained by allowing a base to coexist or act before and after the reaction. Examples of the base in such a case include sodium hydride, sodium,
For example sodium ethylate, sodium methylate,
Alkali metal alcoholates such as potassium tert-butoxide, organic bases such as triethylamine, diisopropylethylamine, pyridine, N, N-dimethylaniline, such as potassium carbonate, sodium carbonate, sodium hydroxide, potassium hydroxide, sodium hydrogen carbonate,
An inorganic base such as potassium hydrogen carbonate can be used.
The amount of the base used is not particularly limited as long as it does not adversely affect the reaction, and a large excess amount can also be used as a solvent as in the case of pyridine, for example.

The amount of acylating agent used in the reaction is
The amount is 1 to 5 times, and preferably 1 to 2.5 times the molar amount of [V] or [VII].

The temperature used in the reaction is usually -50 to 20.
It is 0 ° C., preferably −30 to 50 ° C. The reaction time is generally 0.1 to 24 hours, preferably 0.1 to 1
It's 0 hours. The obtained compound is a means known per se,
For example, concentration, vacuum concentration, liquid conversion, phase transfer, solvent extraction,
After separation and purification by distillation, crystallization, recrystallization, chromatography or the like, the reaction mixture may be directly used as a starting material for the next reaction.

In the reaction [V] → [VIII], RS of the compound [V] or a salt thereof is, for example, C _1-4 alkylthio such as methylthio or C _7-10 such as benzylthio.
Aralkylthio and the like are particularly preferable. Compound [VI] or a salt thereof is about 0.8 in comparison with compound [V] or a salt thereof.
It is preferable to use about 2.0 to 2.0 equivalents, but about 2.0 to 20 equivalents may be used if the reaction is not hindered.

The reaction may be carried out without solvent, but it is usually carried out in a suitable solvent. Examples of such a solvent include water, methanol, ethanol, n-propanol,
Alcohols such as isopropanol, benzene, toluene, aromatic hydrocarbons such as xylene, dichloromethane,
Halogenated hydrocarbons such as chloroform, saturated hydrocarbons such as hexane, heptane, cyclohexane, ethers such as diethyl ether, tetrahydrofuran, dioxane, ketones such as acetone, nitriles such as acetonitrile, sulfoxides such as dimethyl sulfoxide. Kind,
Acid amides such as N, N-dimethylformamide, esters such as ethyl acetate, and carboxylic acids such as acetic acid and propyroic acid are used. These solvents may be used alone or, if necessary, two or more kinds may be mixed and used in an appropriate ratio, for example, in a ratio of 1: 1 to 1:10. If the reaction mixture is not in homogeneous phase, for example triethylbenzylammonium chloride,
The reaction may be carried out in the presence of a quaternary ammonium salt such as tri-n-octylmethylammonium chloride, trimethyldecylammonium chloride or tetramethylammonium bromide, or a phase transfer catalyst such as crown ethers.

In this reaction, 0.01 to 1 of a base or a metal salt is used.
It may be promoted by adding 0 equivalent, preferably 0.1 to 3 equivalent. Examples of such a base include sodium hydrogen carbonate, potassium hydrogen carbonate, sodium carbonate, potassium carbonate, sodium hydroxide, potassium hydroxide, calcium hydroxide, phenyl lithium, butyl lithium, sodium hydride, potassium hydride, sodium methoxide. , Inorganic bases such as sodium ethoxide, sodium metal, and metal potassium, such as triethylamine, tributylamine, N, N-dimethylaniline, pyridine, lutidine, collidine, 4- (dimethylamino) pyridine, D
An organic base such as BU (1,8-diazabicyclo [5,4,0] undecene-7) can be used. The organic base may be used as a solvent itself. Further, as the metal salt, for example, copper salts such as copper chloride, copper bromide, copper acetate, copper sulfate, and mercury salts such as mercury chloride, mercury nitrate, and mercury acetate can be used.

The reaction temperature of this reaction is usually from -20 to 150.
The reaction temperature is usually 10 minutes to 50 hours, preferably 0 to 100 ° C. and 1 to 20 hours, respectively.

RS in the reaction [VII] → [IX]
Of [V] → [VIII]
The same as described in the reaction of.

[I] → [V] and [I] → [VII]
In each reaction of

[Chemical 28] An imide compound represented by is by-produced. [V] or [VII] and the imide compound can often be separated by a known means such as chromatography. However, when the separation is difficult, the reaction mixture is dissolved in a basic aqueous solution and gradually neutralized with an acid. However, the imide compound is decomposed into a di (thio) carboxylic acid monoamide derivative or the like by a method of separately precipitating [V], [VII] and the imide compound or by stirring in a basic aqueous solution. It is also possible to separate them by a method of mixing and precipitating [V] or [VII]. Examples of the base used in this separation method include inorganic bases such as sodium carbonate, potassium carbonate, sodium hydroxide, potassium hydroxide and calcium hydroxide, such as triethylamine, tributylamine, N, N-dimethylaniline, pyridine and lutidine. , Collidine, 4- (dimethylamino) pyridine, DBU (1,8-diazabicyclo [5,4,0] undecene-7), and other organic bases can be used.
Examples of the acid used for the neutralization of the separation method include hydrochloric acid, hydrobromic acid, hydroiodic acid, phosphoric acid, sulfuric acid,
An inorganic acid such as perchloric acid, for example, an organic acid such as formic acid, acetic acid, tartaric acid, malic acid, citric acid, oxalic acid, succinic acid, benzoic acid, picric acid, p-toluenesulfonic acid can be used.

Further, the separation method is [I] → [V] →
It can also be used as a method for separating [VIII] or [IX] and an imide compound after carrying out a two-step reaction such as [VIII] or [I] → [VII] → (IX].

The resulting compound [VIII] or (I
X] or a salt thereof is known per se, for example, concentration,
It can be isolated and purified by concentration under reduced pressure, liquid conversion, phase transfer, solvent extraction, crystallization, recrystallization, chromatography and the like.

In some cases, the compounds [I] and / or [V] and / or [VII] are the desired compounds [VII].
I] and / or [IX] can be converted after being isolated temporarily or as it is in the reaction solution.

The compounds [VIII] and / or (IX) are converted to the starting materials [II] and [II] via the compound [I].
I] can be obtained without purification and / or isolation of intermediates.

The guanidine derivative thus obtained [VI
II] or [IX] is obtained as a free compound, for example, hydrochloric acid, hydrobromic acid, hydroiodic acid, phosphoric acid,
Inorganic acids such as sulfuric acid and perchloric acid, for example, salts with organic acids such as formic acid, acetic acid, tartaric acid, malic acid, citric acid, oxalic acid, succinic acid, benzoic acid, picric acid, p-toluenesulfonic acid, etc. Can be converted according to.

When R ³ (or R ^3a ) is hydrogen and when R ¹ (or R ^1a ) or R ² is hydrogen, a metal salt such as sodium salt, potassium salt or lithium salt is prepared by a conventional method. , A triethylammonium salt, a tetrabutylammonium salt and the like, and a salt with an organic base can be converted.

When it is obtained in the form of a salt, it can be converted into a free compound by a conventional method. As the salts of the compounds [IV], [V], [VI] and [VII], for example, the salts as mentioned in the above [VIII] or [IX] may be used.

The guanidine derivative [VIII] or [IX] or a salt thereof produces cis and trans stereoisomers with respect to the position of the X group, and R ³ (or R ^3a ) is hydrogen and R ¹ ( Alternatively, when R ^1a ) or R ² is hydrogen, a tautomer is theoretically produced, and any of these isomers is a compound of the present invention [VIII].
Alternatively, it is included in [IX] or a salt thereof.

[Chemical 29]

The guanidine derivative [VIII] or [IX] and its salt are effective in controlling hygienic pests and animal and plant parasitic insects, and are strong by direct contact with insects such as direct spraying on the animal and plant parasitic on the insect pests. It has an insecticidal action, but as a more characteristic property, the drug is a root,
This is because once the plant absorbs it from the leaves, stems, etc., and then the insect sucks, chews, or comes into contact with the plant, it exerts a strong insecticidal action. Such properties are
It is advantageous for combating biting insects. In addition, the compounds [VIII], [IX] and salts thereof have a low phytotoxicity to plants and a low toxicity to fish.
It has both safe and advantageous properties as a pest control agent for gardening, especially for agriculture.

Guanidine derivatives [VIII] and [IX]
Or, when using the salt as an insecticide, a general pesticide can take a form, that is, a compound [VIII],
[IX] or one or more kinds of salts thereof are dissolved or dispersed in a suitable liquid carrier or mixed or adsorbed with a suitable solid carrier depending on the purpose of use, and emulsion, oil, wettable powder, powder It is used as a dosage form for granules, tablets, sprays, ointments and the like. These formulations can be formulated, if necessary, with emulsifiers, suspensions, spreading agents, penetrants, wetting agents, mucilages,
Stabilizers and the like may be added, and they can be prepared by a method known per se.

The content ratio of the active ingredient in the insecticide varies depending on the purpose of use, but an emulsion, a wettable powder or the like is preferably about 10 to 90% by weight, and an oil or powder is 0.1 to 90% by weight.
About 10% by weight is suitable, and 1-20% by weight is suitable as the granule, but these concentrations may be appropriately changed depending on the purpose of use. Emulsions, wettable powders, etc. may be diluted appropriately with water before use (eg 100 to 100,
000 times) and spray.

The liquid carrier (solvent) used is, for example, water, alcohols (eg, methyl alcohol, ethyl alcohol, n-propyl alcohol, isopropyl alcohol, ethylene glycol, etc.), ketones (eg, acetone, methyl ethyl ketone, etc.). , Ethers (eg dioxane, tetrahydrofuran, ethylene glycol monomethyl ether, diethylene glycol monomethyl ether, propylene glycol monomethyl ether etc.), aliphatic hydrocarbons (eg kerosene, kerosene, fuel oil, machine oil etc.), aromatic hydrocarbons Classes (eg benzene, toluene, xylene, solvent naphtha, methylnaphthalene etc.), halogenated hydrocarbons (eg dichloromethane, chloroform, carbon tetrachloride etc.) Acid amides (e.g. dimethylformamide, dimethyl acetamide), esters (e.g., ethyl acetate, butyl acetate, fatty acid glycerol ester), a nitrile (e.g. acetonitrile, propionitrile, etc.) solvent suitable,
These can be appropriately used by mixing one kind or two kinds or more in an appropriate ratio.

As the solid carrier (diluting / extending agent), vegetable powder (eg soybean powder, tobacco powder, wheat flour, wood powder, etc.), mineral powder (eg kaolin, bentonite, clay such as acid clay, talc) Powder, talc such as wax stone powder, diatomaceous earth, silica such as mica powder, etc., alumina, sulfur powder, activated carbon, etc. are used, and one kind or two or more kinds thereof are appropriately mixed and used. be able to.

Examples of the ointment base include polyethylene glycol, pectin, polyhydric alcohol esters of higher fatty acids such as glyceryl monostearate, cellulose derivatives such as methyl cellulose, sodium alginate, bentonite, higher alcohols such as glycerin. Polyhydric alcohol, petrolatum, white petrolatum, liquid paraffin, lard, various vegetable oils, lanolin, dehydrated lanolin, hardened oil, resins and the like, or one or more kinds thereof, or various surfactants shown below are added. Those obtained are appropriately used.

As the surfactant used as an emulsifier, a spreading agent, a penetrating agent, a dispersant, etc., if necessary, soaps, polyoxyethylene alkylaryl ethers [eg, Neugen ^R , E A 142 ( E ・ A14
2 ^R ); manufactured by Dai-ichi Kogyo Seiyaku Co., Ltd., Nonal ^R ; manufactured by Toho Kagaku Co., Ltd.], alkylsulfates [eg, Emar 10 ^R ,
Emal 40 ^R; manufactured by Kao Corp.], alkylsulfonic acid salts [eg, Neogen ^R, NEOGEN ^{T R;} Dai-ichi Kogyo Seiyaku Co., Ltd., Neoperex; manufactured by Kao Corporation], polyethylene glycol ethers [e.g. , Nonipol 85 ^R , nonipol 100 ^R , nonipol 160 ^R ; manufactured by Sanyo Kasei Co., Ltd., polyhydric alcohol esters [eg, Tween 20 ^R , Tween 80 ^R ; manufactured by Kao Co., Ltd.] A system surfactant is used as appropriate.

Further, a guanidine derivative [VIII],
[IX] or a salt thereof and, for example, other kinds of insecticides (pyrethroid insecticides, organophosphorus insecticides, carbamate insecticides, natural insecticides, etc.), acaricides, nematicides, herbicides, plant hormones Agents, plant growth regulators, bactericides (eg copper bactericides, organic chlorine bactericides, organic sulfur bactericides, phenolic bactericides, etc.), synergists, attractants, repellents, pigments, fertilizers, etc. It is also possible to mix and use appropriately.

Guanidine derivatives [VIII], (IX)
Insecticides containing or (and) salts thereof are specifically, for example, the turtle ( Eurydema rugosum ), the rice stink bug ( Scotinophala lurid).
a ), Rabbit bug ( Riptortus cla)
Vatus ), Nasigumbai ( Stephanitis )
nashi ), Japanese planehopper ( Laodelfa )
x striatellus ), brown planthopper ( Ni
laparvata lugens ), Green leafhopper ( Nephotettix cincticep )
s ), Japanese scale insect ( Unaspis yano)
Nensis ), soybean aphid ( Aphis gl)
ycinees ), aphid aphid ( Lipap)
his erysimi ), Japanese radish aphid ( Br
helicopterous pests such as E. cinebrassicae ) and cotton aphid ( Aphis gossypii ), for example, Spodoptera ( Spodoptera)
itura ), diamondback moth ( Plutella xylos )
tella ), Pieris rap ( Pieris rap )
ae crucivora ), Nikameiga ( Chilo
suppressalis), Tamanagin'uwaba (A
utographa nigrisigna ), tobacco moth ( Helicoverpa assulta ), armyworm ( Pseudaletia separat )
a ), Spodoptera frugiperda ( Mamestra brassica )
e ), Apple cockroach ( Adoxophies)
orana fasciata ), cotton bollworm ( N
otarcha derogata ), Cnaphalocross medinali
s ), potato moth ( Phthorimaea ope)
rculella ) and other pests of the order Lepidoptera, for example, Epilachna viginio
ctopuncata , urchin beetle ( Aulaco
phora femoralis ), Phyllotreta striolata , Olema oryzae , Weevil ( Echinocnemus squameu )
s ) and other beetle pests such as the housefly ( Musca d)
omestica ), Culex pipiens ( Culex pipe )
iens pallens ), cattle fly ( Tabanu )
s trigonus ), onion fly ( Delia )
antiqua ), fly ( Delia platu )
Ra ) and other dipteran pests, such as the locust locust ( Loc)
usta migratoria ), Kera ( Gryll )
Orthoptera pests such as Otalpa africana ), such as the German cockroach ( Blattella germ)
anica ), Black cockroach ( Periplaneta )
cockroaches pests such as fuliginosa , for example, Tetranychus urtica
e ), citrus red mite ( Panychus citr )
i ), Kanzawa no Mite ( Tetranychus ka )
nzawai), carmine spider mite (Tetranych
us cinnabarinus ), apple spider mite ( P
anonychus ulmi ), citrus rust mite ( A
pests such as culops pelekassi ),
For example, rice pineapple ( Aphelencho)
It is particularly effective for controlling nematodes such as ides besseyi ).

The insecticide thus obtained is a safe and excellent pesticide with very little toxicity. Then, the insecticide of the present invention can be used in the same manner as conventional insecticides, and as a result, it can exhibit superior effects as compared with conventional products. For example, the insecticide of the present invention can be used for target pests by, for example, seedling raising box treatment, crop foliage application, insect body application, paddy field underwater application or soil application. And the application amount, the application time, application place,
It can be varied over a wide range depending on the application method, etc., but generally 0.3 g to 0.1 g of the active ingredient (guanidine derivative [VIII] or / and its salt) per hectare.
It is desirable to apply 3,000 g, preferably 50 to 1,000 g. When the insecticide of the present invention is a wettable powder, the final concentration of the active ingredient is 0.1 to 0.1.
It may be used by diluting it in the range of 1,000 ppm, preferably 10 to 500 ppm.

[0066]

The present invention will be described in more detail with reference to examples, but the present invention should not be construed as being limited to these examples.

Elution by column chromatography in Examples and Reference Examples was carried out by TLC (Thin Layer C).
(chromatography, thin layer chromatography). In TLC observation, as a TLC plate, Kieselgel 60F ₂₅₄ (70 to 230 mesh) manufactured by Merck Co., Ltd.
Was used as a developing solvent, and a solvent used as an elution solvent in column chromatography was used as a developing solvent, and a UV detector was used as a detection method. As the silica gel for the column, Kieselgel 60 (70 to 230 mesh) also manufactured by Merck was used.
The NMR spectrum shows proton NMR, using tetramethylsilane as an internal standard, VARIANEM3
90 (90MHZ) type or Hitachi R-600 (60
MHZ) type spectrometer and measure all δ values by pp
Indicated by m. When a mixed solvent is used as the developing solvent, the numerical value shown in parentheses is the volume mixing ratio of each solvent.

The abbreviations used in the following Examples and Table 1 have the following meanings.

Me: methyl group, Et: ethyl group, Ph:
Phenyl group, S: singlet, br: broad (wide), d: doublet, t: triplet, q: quartet, m: multiplet, dd: doublet doublet, J: coupling constant, Hz: Hertz, CDCl.
₃ : Deuterated chloroform, DMSO-d ₆ : Deuterated DMSO,
%: Wt%, mp: melting point Also, room temperature is about 15 to
Means 25 ° C.

Example 1 5 g of S-methyl-N-nitroisothiourea and 7 of pyridine
0 ml of the mixture was ice-cooled, and 14.5 g of phthaloyl chloride was added dropwise over 30 minutes. After stirring for 10 minutes under ice cooling,
The crystals were poured into ice-cooled dilute hydrochloric acid (concentrated hydrochloric acid 100 ml, water 500 ml), and the resulting crystals were collected by filtration. 50ml EtO to this
Recrystallization was carried out by adding H to obtain 8.0 g of S-methyl-N-nitro-N'-phthaloylisothiourea as white needle crystals. mp 138 to 140 ° C. ¹ H NMR (CDCl ₃ ): 8.10 to 7.80 (4
H. m), 2.64 (3H, s).

Example 2 A mixture of 2 g of S-methyl-N-nitro-N'-phthaloylisothiourea and 20 ml of acetonitrile was ice-cooled to 5
-Aminomethyl-2-chlorothiazole 1.1 g 10
Dropped in minutes. After stirring under ice cooling for 30 minutes, the mixture was concentrated, and the residue was purified by column chromatography (developing solvent; chloroform-ethanol (20: 1)),
Obtained 1.93 g of N- (2-chloro-5-thiazolylmethyl) -S-methyl-N'-nitroisothiourea as a pale yellow powder. mp 162.5 to 165 ° C. ¹ H-NMR (DMSO-d ₆ ): 9.20 to 8.60.
(1H.br), 7.53 (1H, s), 4.72 (2
H, d, J = 5.0 Hz), 2.44 (3H, s).

Example 3 A mixture of 300 mg of S-methyl-N-nitro-N'-phthaloylisothiourea and 10 ml of acetonitrile was ice-cooled, and 150 mg of benzylamine was added dropwise over 10 minutes.
After stirring under ice-cooling for 15 minutes, the mixture was concentrated, the residue was purified by column chromatography (developing solvent; n-hexane-ethyl acetate (1: 1)), and 248 mg of N-benzyl-S-methyl- N'-nitroisothiourea was obtained as a white powder. mP 77-80 ° C. ¹ H-NMR (DMSO-d ₆ ): 10.20-8.2
0 (1H.br), 7.32 (4H, s), 4.64
(2H, s), 2.46 (3H, s).

Example 4 N- (2-chloro-5-thiazolylmethyl) -S-methyl-N'-nitroisothiourea 1 g, acetonitrile 3
To 0 ml of the mixture, 349 mg of a 40% methylamine methanol solution was added dropwise at room temperature over 5 minutes. After stirring for 1.5 hours, the white precipitate formed was filtered off and dried to 410 mg.
N- (2-chloro-5-thiazolylmethyl) -N'-
Methyl-N "-Nitcoguanidine (Compound No. 14)
Was obtained as a white powder. The mother liquor collected by filtration was concentrated, 20 ml of ethanol was added, the mixture was stirred well, and the crystals were collected by filtration to obtain 330 mg of compound No. 14 (mP 172-17
3 ° C.) was obtained. When this product was recrystallized from acetonitrile, it showed mP 173-174 ° C. ¹ H-NMR (DMSO-d ₆ ): 9.15 to 8.75
(1H.br), 7.58 (1H, s), 8.25-
7.90 (1H, br), 4.51 (2H, d, J =
5.0Hz), 2.84 (3H, d, J = 5.0H
z).

Example 5 A mixture of 10 g of S-methyl-N-nitro-N'-phthaloylisothiourea and 100 ml of acetonitrile was ice-cooled to give 2-chloro-5- (aminomethyl) thiazole.
6g was dripped in 10 minutes. After stirring for 30 minutes under ice cooling, the temperature was returned to room temperature, and 3.5 g of a 40% methylamine methanol solution was added dropwise over 5 minutes. After stirring for 1.5 hours, the mixture was concentrated to obtain 14.9 g of a mixture of N- (2-chloro-5-thiazolylmethyl) -N'-methyl-N "-nitroguanidine (Compound No. 14) and phthalimide as a white powder. This was dissolved in an aqueous solution of potassium hydroxide (8.5 g of potassium hydroxide, 80 ml of water), stirred at room temperature for 1 hour, then cooled with ice, and 8 ml of concentrated hydrochloric acid was added little by little. After stirring, the resulting crystals were collected by filtration,
When dried, 8.8 g of Compound No. Only 14 was obtained as a pale yellow powder. This product has the compound and melting point obtained in Example 4,
The Rf values of NMR, IR and TLC were in agreement.

Example 6 To a mixture of 600 mg of N- (2-chloro-5-thiazolylmethyl) -S-methyl-N'-nitroisothiourea and 20 ml of acetonitrile was added dropwise 252 mg of a 50% aqueous dimethylamine solution at room temperature. After stirring at room temperature for 2 hours,
The mixture was concentrated, 20 ml of ethanol was added to the residue, and the mixture was stirred well. The crystals were collected by filtration and dried to obtain 350 mg of N- (2-chloro-5-thiazolylmethyl) -N ', N'-dimethyl-N "-nitroguanidine (Compound No. 17) as a white powder. Mother liquor is concentrated and ethanol 5 ml
Was added and the mixture was stirred well, and the crystals were collected by filtration, dried, and further 1
20 mg of compound No. 17 (mp 154-159)
C) was obtained. When this product is recrystallized from acetonitrile,
mp 164-166 ° C. ¹ H-NMR (DMSO-d ₆ ): 8.70 to 8.35.
(1H, br) 7.51 (1H, s) 4.53 (2H,
br) 3.00 (6H, s).

Example 7 A mixture of 0.5 g of S-methyl-N-nitroisothiourea, 1.5 g of potassium carbonate and 30 ml of acetonitrile was ice-cooled, and 1.5 g of succinic acid chloride was added dropwise over 2 minutes. After stirring under ice-cooling for 1 hour, the mixture was further stirred at room temperature for 30 hours.
Stir for minutes. The insoluble material was collected by filtration, the solvent was evaporated, the residue was dissolved in chloroform, washed with aqueous sodium hydrogen carbonate, dried over anhydrous magnesium sulfate and concentrated. The residue was purified by column chromatography [developing solvent; chloroform-ethanol (10: 1)] to obtain 0.28 g of S-methyl-N-nitro-N'-succinylisothiourea as a white powder. mP 114-115 ° C ¹ H-NMR (CDCl ₃ ): 2.90 (4H, s);
2.60 (3H, s).

Example 8 A mixture of 210 mg of S-methyl-N-nitro-N'-succinylisothiourea and 10 ml of acetonitrile was ice-cooled to give 160 m of 5-aminomethyl-2-chlorothiazole.
g was added dropwise over 30 seconds. After stirring for 10 minutes under ice-cooling, the solvent was distilled off, 12 ml of water was added to the residue for washing, and crystals were collected by filtration. Air dry this to 220 mg N
-(2-Chloro-5-thiazolylmethyl) -S-methyl-N'-nitroisothiourea was obtained as a yellow powder. This product is the compound obtained in Example 2 and melting point, NMR, IR, TL
The Rf values of C matched.

Example 9 A mixture of 0.5 g of S-methyl-N-nitroisothiourea, 1.03 g of potassium carbonate and 10 ml of acetonitrile was ice-cooled, and 1.65 g of glutaric chloride was added dropwise over 2 minutes. After stirring for 1 hour under ice cooling, the mixture was further stirred at room temperature for 1 hour. The insoluble material was filtered off, the solvent was distilled off, and the residue was purified by column chromatography [developing solvent: chloroform-ethanol (10: 1)] to obtain 0.22 g of N-glutaryl-S-methyl-N'-nitroisothiourea. Obtained as a white powder. _{^{mP 147~149 ℃ 1 H-NMR (}} CDCl 3): 2.70 (t, 4H),
2.60 (s, 3H), 1.70-2.30 (m, 2
H).

Example 10 A mixture of 0.18 g of N-glutaryl-S-methyl-N'-nitroisothiourea and 10 ml of acetonitrile was ice-cooled and 0.1 g of 5-aminomethyl-2-chlorothiazole was added.
Was dripped. After stirring under ice cooling for 30 minutes, the mixture was stirred at room temperature for 1 hour. After distilling off the solvent, column chromatography [developing solvent: chloroform-ethanol (1
0: 1)] to obtain 170 mg of N- (2-chloro-5-thiazolylmethyl) -S-methyl-N'-nitroisothiourea as a white powder. This product is Example 2
The melting point, Rf value of NMR, IR, and TLC of the compound obtained in 1. matched.

Example 11 0.5 g of S-methyl-N-nitroisothiourea, 2.06 g of potassium carbonate, 30 ml of acetonitrile, 1 ml of water
The mixture was cooled with ice, and 1.55 g of cis-1,2-cyclohexanedicarboxylic acid chloride was added dropwise over 1 minute.
After stirring under ice cooling for 20 minutes, the mixture was stirred at room temperature for 1 hour. 30 ml of water and 30 ml of chloroform were added to the reaction mixture, and the layers were separated. The aqueous layer was extracted with 100 ml of chloroform. The organic layers were combined, dried and concentrated, and the residue was purified by column chromatography [developing solvent; chloroform-ethanol (10: 1)] to 270 m.
g of N- (cyclohexane-cis-1,2-dicarbonyl) -S-methyl-N'-nitroisothiourea was obtained as a white powder. _{^{mp 112~113 ℃ 1 H-NMR (}} CDCl 3): 2.90-3.20
(M, 2H), 2.60 (s, 3H), 1.30-2.
10 (m, 8H).

Example 12 N- (Cyclohexane-cis-1,2-dicarbonyl) -S-methyl-N'-nitroisothiourea 370 m
The mixture of g and 10 ml of acetonitrile was ice-cooled, and 223 mg of 5-aminomethyl-2-chlorothiazole was added dropwise. After stirring under ice cooling for 30 minutes, the mixture was stirred at room temperature for 1 hour. After distilling off the solvent, column chromatography [developing solvent: chloroform-ethanol (10:
1)] and 170 mg of N- (2-chloro-
5-Thiazolylmethyl) -S-methyl-N'-nitroisothiourea was obtained as a white powder. This product had the same melting point, Rf value of NMR, IR, and TLC as those of the compound obtained in Example 2.

Example 13 A mixture of 0.5 g of S-methyl-N-nitroisothiourea and 20 ml of pyridine was heated to 62 ° C., and a solution of 1.27 g of diglycolic acid dichloride in 2 ml of acetonitrile was added dropwise over 1 minute. After heating and stirring for 80 minutes, the reaction mixture was diluted with hydrochloric acid (concentrated hydrochloric acid 50 ml, water 50 ml, ice 20 g).
And extracted with 90 ml of chloroform. The chloroform layer was washed with 30 ml of sodium bicarbonate water and dried over magnesium sulfate. A small amount of ethyl acetate was added to the oily substance obtained by concentration and the mixture was stirred, and crystals were precipitated, which were collected by filtration and 440 mg of S-methyl-N-nitro-N '-(2,
2'-Oxydiacetyl) isothiourea was obtained as white crystals. mp 132-134 ° C. ¹ H-NMR (CDCl ₃ ): 4.40 (s, 4H),
2.65 (s, 3H).

Example 14 S-Methyl-N-nitro-N '-(2,2'-oxydiacetyl) isothiourea 90 mg, chloroform 9 ml
The mixture was cooled with ice, and a solution of 5-aminomethyl-2-chlorothiazole (100 mg) in chloroform (0.5 ml) was added dropwise. After stirring for 20 minutes under ice cooling and 50 minutes at room temperature, water 1
5 ml and 15 ml of chloroform were added for liquid separation, and the aqueous layer was extracted with 50 ml of chloroform. The obtained organic layers were combined and the solvent was distilled off, followed by purification by column chromatography [developing solvent: chloroform-ethanol (10: 1)] to obtain 30 mg of N- (2-chloro-5-thiazolylmethyl) -S-methyl. -N'-nitroisothiourea was obtained as a white powder. This product had the same melting point, Rf value of NMR, IR, and TLC as those of the compound obtained in Example 2.

Example 15 While a mixture of 1 g of S-methyl-N-nitroisothiourea, 6.15 g of potassium carbonate and 100 ml of acetonitrile was stirred at room temperature, 2.7 g of adipic acid dichloride was added dropwise over 5 minutes. After stirring for 2 hours, the formed crystals were collected by filtration, washed with a small amount of acetonitrile and washed with 470
Obtained mg of N-adipoyl-S-methyl-N'-nitroisothiourea as white crystals. mp 193-194
_{^{℃ 1 H-NMR (CDCl 3}} ): 3.00-2.20
(M, 4H), 2.40 (s, 3H), 2.00-1.
40 (m, 4H)

Example 16 To a mixture of 300 mg of S-methyl-N-nitro-N'-succinylisothiourea and 5 ml of acetonitrile, (6
-Chloro-3-pyridyl) methyl ethylamine 236
mg was added dropwise under ice cooling. After stirring at room temperature for 13 hours, the mixture was concentrated and the residue was dissolved in 100 ml of ethyl acetate to give 50 m.
It was washed twice with 1 l of water. The organic layer was concentrated to give 350 mg of N- (6-chloro-3-pyridylmethyl) -N-ethyl-S-methyl-N'-nitroisothiourea as a light brown oil. ¹ H-NMR (CDCl ₃ ): 8.33 (1 H, b
r), 7.73 (1H, dd, J = 9.0Hz, 2.5
Hz), 7.36 (1H, d, J = 9.0 Hz), 4.
83 (2H, s), 3.65 (2H, q), 2.57
(3H, s), 1.29 (3H, t).

Example 17 In a mixture of 300 mg of S-methyl-N-nitro-N'-succinylisothiourea and 5 ml of acetonitrile, (6
197 mg of -chloro-3-pyridyl) methylamine was added dropwise under ice cooling. After stirring under ice-cooling for 1 hour, the mixture was concentrated, 30 ml of water was added to the residue, and the mixture was stirred well. The crystals were collected by filtration and dried to give 360 mg of N- (6-chloro-3-pyridylmethyl) -S-methyl. -N'-nitroisothiourea was obtained. mp 140-141.5 ° C. ¹ H-NMR (CDCl ₃ + DMSO-d ₆ ): 9.6
0 to 8.90 (1H, br), 8.40 (1H, b
r), 7.78 (1H, dd, J = 9, 0 Hz, 2.5
Hz), 7.33 (1H, d, J = 9.0 Hz), 4.
63 (2H, s), 2.48 (3H, s).

Example 18 N- (2-chloro-5-thiazolylmethyl) -S-methyl-N'-nitroisothiourea 1 g, potassium carbonate 56
0 mg, cuprous chloride 400 mg, acetonitrile 12 m
610 mg of 5-aminomethyl-2-chlorothiazole was added to the mixture of 1 and stirred under reflux for 1 hour. After the reaction, the mixture was concentrated, water was added to the obtained solid, and the mixture was well stirred, then filtered, and purified by column chromatography [developing solvent; dichloromethane-methanol (10: 1)].
191 mg of N, N'-bis (2-chloro-5-thiazolylmethyl) -N "-nitroguanidine (Compound No.
39) was obtained as a white powder. mp 217 to 218 ° C. ¹ H-NMR (DMSO-d ₆ ): 8.95 (2H, b
r), 7.59 (2H, s), 4.60 (4H, b
r).

Example 19 N- (2-chloro-5-thiazolylmethyl) -S-methyl-N'-nitroisothiourea 1 g, acetic anhydride 1.15
A mixture of g and 25 ml of pyridine was stirred at room temperature for 3 hours. The reaction mixture was treated with an aqueous hydrochloric acid solution (concentrated hydrochloric acid 20 ml, water 50
ml and ice 10 g), and the layers were separated. The aqueous layer was extracted with 120 ml of chloroform, the obtained organic layers were combined, dried over magnesium sulfate, and concentrated to give 1.15 g of N-acetyl-N- (2-chloro-5-thiazolylmethyl)-.
S-methyl-N'-nitroisothiourea was obtained as a brown oil. mp 77-78 ° C. ¹ H-NMR (CDCl ₃ ): 7.50 (s, 1H),
4.80 (s, 2H), 2.52 (s, 3H), 2.2
6 (s, 3H).

Next, a mixture of 0.5 g of the obtained compound and 7 ml of chloroform was stirred at -15 ° C. while stirring 130 mg of a 40% methylamine methanol solution in 3 ml of chloroform.
The solution was added dropwise. The mixture was stirred for 2 hours while gradually raising the temperature, concentrated, and purified by column chromatography [developing solvent; chloroform-ethanol (10: 1)] to prepare 1
80 mg of N-acetyl-N- (2-Cucoro-5-thiazolylmethyl) -N'-methyl-N "-nitroguanidine (Compound No. 38) was obtained as a white powder.mp 105-106 ° C ¹ H-NMR. (CDCl ₃ ): 7.50 (1H, s),
4.90 (2H, s), 3.05 (3H, s), 2.2
5 (3H, s).

Example 20 To a mixture of 20 g of S-methyl-N-nitro-N'-phthaloylisothiourea and 300 ml of toluene, a 40% methylamine methanol solution was added dropwise at -7 ° C over 30 minutes. After stirring at -7 ° C for 30 minutes, the resulting crystals were collected by filtration and air-dried to obtain 19.7 g of white crystals. The toluene in the filtrate was concentrated to obtain another 2.7 g of yellow crystals. These crystals were combined and dissolved in an aqueous potassium hydroxide solution (potassium hydroxide 16.9 g, water 160 ml), stirred at room temperature for 1 hour, then ice-cooled, and concentrated hydrochloric acid 16 ml was slowly added dropwise. After stirring for 10 minutes under ice cooling, the resulting crystals were collected by filtration and dried to give 9.8 g of N, S-dimethyl-.
N'-nitroisothiourea was obtained as a pale yellow powder. mp 150-152 ° C. ¹ H-NMR (DMSO-d ₆ ): 8.30-8.95.
(Br, 1H), 2.94 (S, 3H, NMe), 2.
44 (S, 3H, SMe).

Example 21 500 m of N, S-dimethyl-N'-nitroisothiourea
g, potassium carbonate 695 mg, acetonitrile 10 ml
To this mixture was added 376 mg of acetic anhydride at room temperature. After stirring at room temperature for 5 hours, 10 ml of 2N hydrochloric acid was added to 40 m.
It was extracted with 1 l of dichloromethane. The organic layer was washed with saturated aqueous sodium hydrogen carbonate, dried over magnesium sulfate, and concentrated to give N-acetyl-N, S-dimethyl-N'-nitroisothiourea (600 mg) as white crystals. mp 4
0-41 ° C. ¹ H-NMR (CDCl ₃ ): 2.23 (3H, s),
2.52 (3H, s), 3.17 (3H, s).

Then, to a mixture of 300 mg of the obtained compound and 5 ml of dichloromethane, 241 mg of 5-aminomethyl-2-chlorothiazole was dissolved in 1 ml of dichloromethane and added dropwise at -10 ° C. After stirring at -10 ° C for 2 hours, 10 ml of 2N hydrochloric acid was added, the organic layer was separated, dried over magnesium sulfate and concentrated to give 430 mg of a colorless oil. This was dissolved in 5 ml of toluene, 5 ml of n-hexane was added, and the mixture was stirred well to form a white precipitate. It is filtered off, dried and 260 mg of N-acetyl-N '-(2-chloro-5-thiazolylmethyl) -N.
- methyl -N "- nitroguanidine as a white powder _{^{.mp 105~108 ℃ 1 H-NMR (}} CDCl 3): 9.35 (br, 1H)
7.53 (s, 1H) 4.57 (s, 2H) 3.08
(S, 3H) 2.11 (s, 3H).

Example 22 To a mixture of N- (6-chloro-3-pyridylmethyl) -S-methyl-N, -nitroisothiourea (1.3 g) and acetonitrile (10 ml) was added pyridine (1.6 g) and acetyl chloride (0.1 g). 79 g was added dropwise under ice cooling. Under ice cooling 1
After stirring for an hour, the mixture was returned to room temperature and stirred for 2 hours. After concentrating, pouring 50 ml of ether and 5 ml of 2N hydrochloric acid, after liquid separation, the organic layer was dried over magnesium sulfate and concentrated to give 1.6 g of N-acetyl-N- (6-chloro-3- as a red oily substance.
Pyridylmethyl) -S-methyl-N'-nitroisothiourea was obtained. ¹ H-NMR (CDCl ₃ ): 8.39 (d, 1H, J
= 2.0 Hz), 7.72 (dd, 1H, J = 8.0H
z, 2.0 Hz), 7.31 (d, 1H, J = 8.0H
z), 4.75 (s, 2H), 2.50 (s, 3H),
2.28 (s, 3H).

Next, 0.39 g of a 40% methylamine methanol solution was added dropwise to a mixture of the obtained compound (1.6 g) and acetonitrile (10 ml) at -5 ° C. 3 at -3 ° C
After stirring for 0 minutes, the mixture was concentrated, and the obtained yellow oil was subjected to column chromatography [developing solvent: chloroform-ethanol (20: 1)] to give 0.65 g of N-acetyl-.
N- (6-chloro-3-pyridylmethyl) -N, -methyl-N "-nitroguanidine was obtained as a white powder.
_{^{p 124~125 ℃ 1 H-NMR (}} CDCl 3): 9.20 (br, 1
H), 8.32 (d, 1H, J = 2.0 Hz), 7.7
5 (dd, 1H, J = 2.0 Hz, 8.0 Hz), 7.
30 (d, 1H, J = 8.0 Hz), 4.78 (s, 2)
H), 2.98 (d, 3H, J = 5.0 Hz), 2.2
1 (s, 3H).

Reference Example 1 Compound No. 1 obtained in Example 19 180 mg of 38,
190 ml of acetic anhydride at room temperature in a mixture of 5 ml of viridine.
g was added. After stirring at room temperature for 80 minutes, the reaction mixture was poured into an aqueous hydrochloric acid solution (concentrated hydrochloric acid 20 ml, water 50 ml) and separated. The aqueous layer was extracted with 90 ml of chloroform, and the organic layers were combined and dried over magnesium sulfate. After concentration, the product was purified by column chromatography [developing solvent; chloroform-ethanol (10: 1)] to obtain 130 mg of N, N'-diacetyl-N- (2-chloro-5-thiazolylmethyl) -N'-methyl-. N ″ -nitroguanidine was obtained as a white powder.mp 72-74 ° C. ¹ H-NMR (CDCl ₃ ): 7.50 (1H, s),
5.00 (1H, br), 3.20 (1H, br),
2.37 (3H, br), 2.20 (3H, br). According to the production methods of Examples 1 to 22 and the present invention, the following table-
The compound shown in 1 was obtained. The compounds obtained in the above Examples are shown in Table-1.

[0096]

[Table 1]

[0097]

[Table 2]

[0098]

[Table 3]

[0099]

[Table 4]

A) ¹ HNMR (CDCl ₃ ): 3.0
0 (3H, d, J = 4Hz), 4.53 (2H, d, J
= 6 Hz), 6.76 (1H, br.s), 7.46
(1H, d, J = 8Hz), 7.67 (1H, dd, J
= 8.3 Hz), 8.20 (1H, d, J = 3 Hz),
8.83 (1H, br.s). b) ¹ HNMR (CDCl ₃ ): 1.26 (3H,
t, J = 7 Hz), 2.98 (3H, d, J = 2H)
z), 3.47 (2H, q, J = 7Hz), 4.70.
(2H, s), 7.50 (1H, s), 7.96 (1
H, br. s). c) ¹ HNMR (CDCl ₃ ): 3.00 (3H,
d, J = 4 Hz), 3.09 (3H, s), 4.69
(2H, s), 7.50 (1H, s), 8.00 (1
H, br. s). d) ¹ HNMR (CDCl ₃ ): 1.23 (6H,
t, J = 7 Hz), 3.46 (4H, q, J = 7.2H)
z), 4.60 (2H, br.s), 7.44 (1H,
s), 8.30 (1H, br.s). e) ¹ HNMR (CDCl ₃ ): 3.11 (6H,
s), 4.42 (2H, d, J = 6Hz), 6.86
(1H, s), 7.07 (1H, t, J = 60Hz),
7.78 (1H, br.t, J = 6Hz). f) ¹ HNMR (DMSO-d ₆ ): 9.70-9.
00 (1H, br), 8.68 (1H, s), 7.55
(1H, s), 4.95 (2H, s), 2.93 (3
H, d, J = 4Hz)

[0101]

INDUSTRIAL APPLICABILITY The present invention provides a production method advantageous for industrially mass-producing a novel guanidine derivative having excellent insecticidal activity or a salt thereof.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁵ Identification code Internal reference number FI Technical display location C07C 335/40 8619-4H 335/42 8619-4H C07D 209/48 213/36 6701-4C 213 / 61 6701-4C 239/26 7038-4C 277/28 7019-4C 277/32 7019-4C 307/66 7729-4C 333/36 7729-4C C07F 9/572 Z 7106-4H // A01N 47/28 8930- 4H 102 8930-4H

Claims (7)

[Claims] 1. The formula: [Wherein R is an optionally substituted hydrocarbon group or an acyl group, X is an electron withdrawing group, Y ¹ and Y ² are the same or different and are oxygen or sulfur, and A is optionally substituted. It shows a good divalent hydrocarbon group. ] The compound represented by these. 2. The formula: [In the formula, R represents an optionally substituted hydrocarbon group or an acyl group, and X represents an electron-withdrawing group. ] And a compound of the formula: [Wherein A is an optionally substituted divalent hydrocarbon group, Y ¹ and Y ² are the same or different and are oxygen or sulfur, and Z ¹ and Z ² are the same or different and are halogen or Together they show oxygen. ] It is characterized by reacting with a compound represented by: [Wherein R is an optionally substituted hydrocarbon group or an acyl group, X is an electron withdrawing group, Y ¹ and Y ² are the same or different and are oxygen or sulfur, and A is optionally substituted. It shows a good divalent hydrocarbon group. ] The manufacturing method of the compound represented by these. 3. The formula: [Wherein R is an optionally substituted hydrocarbon group or an acyl group, X is an electron withdrawing group, Y ¹ and Y ² are the same or different and are oxygen or sulfur, and A is optionally substituted. It shows a good divalent hydrocarbon group. And a compound represented by the formula: R ¹ R ² NH [wherein R ¹ and R ² are the same or different and each is hydrogen or an optionally substituted hydrocarbon group, or together is a cyclic amino group together with an adjacent nitrogen. Indicates. ] Reaction with an amine or a salt thereof represented by the formula: [The symbols in the formula have the same meanings as described above. ] The manufacturing method of the compound or its salt represented by these. 4. The formula: [Wherein R is an optionally substituted hydrocarbon group or an acyl group, X is an electron withdrawing group, Y ¹ and Y ² are the same or different and are oxygen or sulfur, and A is optionally substituted. It shows a good divalent hydrocarbon group. And a compound represented by the formula: R ¹ R ² NH [wherein R ¹ and R ² are the same or different and each is hydrogen or an optionally substituted hydrocarbon group, or together is a cyclic amino group together with an adjacent nitrogen. Indicates. ] The amine obtained by reacting with an amine or a salt thereof represented by the following formula: [The symbols in the formula have the same meanings as described above. ] When R ¹ represents a hydrogen atom, the compound represented by the following formula is optionally acylated, and then R ³ -NH (CH ₂ ) n-B [wherein B is substituted and Is a homo or heterocyclic group, n is 0 or 1, and R ³ is hydrogen or an optionally substituted hydrocarbon group. ] The compound represented by the formula or a salt thereof is reacted with the compound represented by the formula: [In the formula, B, n and R ³ are as defined above, R ^1a is a hydrogen atom, an optionally substituted hydrocarbon group or an acyl group, and other symbols are as defined above. ] The manufacturing method of the compound or its salt represented by these. 5. The formula: [Wherein R is an optionally substituted hydrocarbon group or an acyl group, X is an electron withdrawing group, Y ¹ and Y ² are the same or different and are oxygen or sulfur, and A is optionally substituted. It shows a good divalent hydrocarbon group. And a compound represented by the formula: R ³ —NH (CH ₂ ) nB [wherein B is an optionally substituted homolog or heterocyclic group, n is 0 or 1, R ³ is hydrogen or The hydrocarbon group which may be substituted is shown. ] The compound represented by the formula or a salt thereof is reacted with the compound represented by the formula: [The symbols in the formula have the same meanings as described above. ] The manufacturing method of the compound or its salt represented by these. 6. The formula: [Wherein R is an optionally substituted hydrocarbon group or an acyl group, X is an electron withdrawing group, Y ¹ and Y ² are the same or different and are oxygen or sulfur, and A is optionally substituted. It shows a good divalent hydrocarbon group. And a compound represented by the formula: R ³ —NH (CH ₂ ) nB [wherein B is an optionally substituted homolog or heterocyclic group, n is 0 or 1, R ³ is hydrogen or The hydrocarbon group which may be substituted is shown. ] The compound of the formula: [The symbols in the formula have the same meanings as described above. ] When R ³ represents a hydrogen atom, the compound represented by the following formula is optionally acylated, and then the compound of the formula R ¹ R ² NH [in the formula, R ¹ and R ² are the same or different from each other and are hydrogen. Or, it represents a hydrocarbon group which may be substituted or together represents a cyclic amino group together with an adjacent nitrogen. ] The compound represented by the formula: [In the formula, R ¹ and R ² are as defined above, R ^3a is a hydrogen atom, an optionally substituted hydrocarbon group or an acyl group, and other symbols are as defined above. ] The manufacturing method of the compound or its salt represented by these. 7. The formula: [R represents a hydrocarbon group or an acyl group which may be substituted, and X represents an electron withdrawing group. ] And a compound of the formula: [Wherein A is an optionally substituted divalent hydrocarbon group, Y ¹ and Y ² are the same or different and are oxygen or sulfur, and Z ¹ and Z ² are the same or different and are halogen or Together they show oxygen. A compound represented by the formula: R ¹ R ² NH [wherein R ¹ and R ² are the same or different and each represents a hydrogen atom or an optionally substituted hydrocarbon group, or Together they represent a cyclic amino group with the adjacent nitrogen. ] In reacting the amine or a salt thereof, later R ^1, if needed next is optionally acylated When hydrogen formula ^{R 3 -NH (CH 2) n} -B wherein , B represents an optionally substituted homologous or heterocyclic group, n represents 0 or 1, and R ³ represents hydrogen or an optionally substituted hydrocarbon group. Compounds represented by] or is reacted with a salt thereof, or wherein ^{R 3 -NH (CH 2) n} -B [wherein each symbol is as defined above. ] When it is reacted with a compound represented by the formula or a salt thereof, and then optionally acylated when R ³ represents a hydrogen atom, the compound is of the formula R ¹ R ² NH [wherein each symbol is as defined above]. Is. ] Reaction with an amine or a salt thereof represented by the formula: [In the formula, R, X, R ¹ , R ² , R ³ , B and n are as defined above, and R ^1a and R ^{3a each} independently represent hydrogen, an optionally substituted hydrocarbon group or an acyl group. As shown, or additionally R ^1a and R ² may together represent a cyclic amino group with the adjacent nitrogen. ] The manufacturing method of the compound or its salt represented by these.