KR800001148B1 - Method for preparing 4,5-dichloroimidazole-2-carboxylic acid derivative - Google Patents

Abstract

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Description

Method for preparing 4,5-dichloroimidazole-2-carboxylic acid derivative

The present invention relates to a process for the preparation of the 4,5-dichloroimidazole-2-carboxylic acid derivative of the following structural formula (I) useful as an insecticide.

그룹은 헤테로 원자와 결합하는 3개의 결합을 갖는 탄소원자를 나타낸다. 살충제란 식물이나 동물에 대한 해충을 이들이 해를 끼치고 있는 곳으로부터 제거하는데 사용되는 약이다.In the above structural formula

A group represents a carbon atom having three bonds bonded to a hetero atom. Insecticides are drugs used to remove pests against plants and animals from where they are causing harm.

It is known that benzimidazole-2-carboxylic acids such as benzimidazole-2-carboxylic acid nitrile have herbicidal action (Netherlands Patent No. 7,004,376). However, the melting of these compounds is not satisfactory, especially when used at low concentrations.

It has been found that the compounds of the present invention have insecticidal action.

The compounds according to the invention are reacted with 4,5-dichloro-2-dichloromethylene-imidazole of formula (II) in the presence of a nucleophilic reagent of formula (II), optionally in the presence of an acid binder and / or water, or a reaction product. Is treated with water and optionally the reaction product is prepared by converting these to salts with a base.

양이온으로서 여기에서 R은 수소 또는 알킬, 아릴, 사이클로 알킬 또는 아르알킬그룹을 나타내며 2 또는 3개의 R 부위는 5-또는 6-원을 환을 형성하며 또는 R¹⁰은 C_1-18-알킬 또는C_3-12-알케닐[이들은 어느것이든 임의로 염소, 불소, 룹롬, 아실옥시로 치환될 수 있으면 여기서 아실은 지방족, 지환족 또는 방향족 카록실산이나 구조식

의 기 C_1-4알콕시, C_1-4알콕시-C_1∼4-알콕시, 페녹시 또는 나프톡시(이들은 어느것이든 임의로 할로겐, C_1-4알킬, CF₃또는 NO₂등으로 치환된다)C_1-4-알킬메르캅토(임의로 할로겐이나 C_1-4알킬에 의해 임의 치환된 페닐로 치환된다)아릴 메르캅토 아릴설포닐 또는 아릴 설포닐(이들중 어느것이나 C_1-4-알킬 또는 할로겐으로 치환될 수 있다.)Z in the above formula represents halogen, azide group or -0-R ¹⁰ or -SR ¹⁰ group and R ¹⁰ is hydrogen, metal cation or

As a cation wherein R represents hydrogen or an alkyl, aryl, cycloalkyl or aralkyl group and two or three R moieties form a 5- or 6-membered ring or R ¹⁰ is C _1-18 -alkyl or C _3-12 -alkenyl [these may be optionally substituted with chlorine, fluorine, chlorom, acyloxy where acyl is aliphatic, cycloaliphatic or aromatic carboxylic acid or structural formula

Groups C _1-4 alkoxy, C _1-4 alkoxy-C _1-4 -alkoxy, phenoxy or naphthoxy, which are optionally substituted with halogen, C _1-4 alkyl, CF ₃ or NO _2, etc. _1-4 -alkylmercapto (optionally substituted with halogen or phenyl optionally substituted by C _1-4 alkyl) Aryl mercapto arylsulfonyl or aryl sulfonyl (any of which is C _1-4 -alkyl or halogen May be substituted.)

의 그룹을 나타내며 여기서 R¹¹과 R¹²는 서로 같거나 다른 것으로서 각각 수소, C_1~12알킬 또는 C_3~8-알케닐[이들은 임의로염소, 불소, 브롬, OH, C_1-4-알콕시, 페녹시(이것은 임의로 C_1-4-알킬, 할로겐 또는 C_1-4-알콕시로 치환될 수 있다), 아실옥시기

C_1-4-알킬메르캅토(임의로 페닐로 치환될 수 있다),페닐 메르캅토(임의로 할로겐 또는 C_1-4알킬로 치환된다),-CN,-COOH,-CONH₂,-CONH(C_1-4-알킬),-CON(C_1-4-알킬)₂,-CONH -아릴 또는 아릴(아릴 그룹은 입의로 할로겐, C_1-4-알킬, CF₃, C_1-4-알콕시 또는 NO₂등으로 치환된 페닐 또는 나프틸이다), 사이클로펜틸,사이클로헥실, 5-또는 6-원복소환 또는

그룹이며 여기서 R¹¹은 상기 언급한 기중 하나 나타낸다.]C _1-4 alkyl sulfonyl, acylamino or diacylamino where acyl represents an aliphatic, cycloaliphatic, araliphatic, aromatic or cyclocyclic carboxylic acid or carboxylic acid or thiocarboxylic acid derivative), CN, carboxylic acid ester Or a cycloalkyl having a ring of 5 to 6 carbon atoms, phenyl (optionally substituted with halogen C _1-4 -alkyl or C _1-4 -alkoxy) or 5- or 6-membered heterocycle], C _3-12 -Alkynyl, cycloalkyl having 3 to 6 carbon atoms (optionally halogen, C _1-4 -alkoxy or C _1-4 alkyl) or phenyl or naphthyl, which may be optionally C _1-4 -alkyl, 1 to C Polyhalogenoalkyl, halogen, C _1-4 -alkoxy, phenoxy or phenyl mercapto of 4 (whichever is optionally halogen, C _1-4 -alkyl, CF ₃ , C _1-4 -alkoxy or NO ₂ ) C _1-4 -alkyl mercapto, C _1-4 -alkylsulfonyl, alkoxy carbonyl, aminocarbonyl C N, NO ₂ or mono- or dialkyl amino having 1 to 4 carbon atoms for each alkyl group; or Z is

Wherein R ¹¹ and R ¹² are the same as or different from each other and are hydrogen, C _1-12 alkyl or C _3-8 -alkenyl [these are optionally chlorine, fluorine, bromine, OH, C _1-4 -alkoxy, phenoxy (which is optionally C _1-4 - alkyl, halogen or C _1-4 - may be substituted with alkoxy), an acyloxy group

C _1-4 -alkyl mercapto (optionally substituted with phenyl), phenyl mercapto (optionally substituted with halogen or C _1-4 alkyl), -CN, -COOH, -CONH ₂ , -CONH (C _{1 -4} -alkyl), -CON (C _1-4 -alkyl) ₂ , -CONH -aryl or aryl (aryl groups are optionally halogen, C _1-4 -alkyl, CF ₃ , C _1-4 -alkoxy or Phenyl or naphthyl substituted with NO ₂ or the like), cyclopentyl, cyclohexyl, 5- or 6-membered heterocycle or

And R ¹¹ represents one of the aforementioned groups.]

의 아실 그룹을 나타내며 R¹³은 수소, C_1-12알킬, 또는 C_2-8알케닐[이들은 임의로 할로겐, C_1-4-알콕시, 페녹시(그자신이 임의로 할로겐, 메틸 또는 NO₂에 의해 치환), C_1-4알킬 메르캅토, 페닐메르캅토(그자신이 임의로 할로겐이나 메틸로 치환됨), 또는 페닐(그 자신이 임의로 할로겐이나 C_1-4알킬로 치환됨)등으로 치환될 수 있다], C_1-4알키닐, 탄소수 3 내지 8환을 가진 사이클로알킬, 페닐 또는 나프틸(이 둘중 어느것이든 임의로 할로겐, C_1-4알콕시, C_1-4알킬,CF₃또는 NO₂에 의해 치환될 수 있다.) 또는 O,S 또는 N등의 복소원자를 함유하는 5- 또는 6-원 복소환을 나타내며 [R¹⁴는 구조식

의 그룹을 나타내며 여기서 R¹⁴는 C_1-12알킬, C_3-12알케닐 또는 C3-12아키닐]이들은 각각 임의로 할로겐, 알콕시,페닐(그자신이 임의로 할로겐 또는 C_1-4킬킬로 치활됨) O,S 또는 N을 함유한 탄소수 5 또는 6의 환을 가진 사이클로 알킬로 치환될 수 있다. 탄소수 5 또는 6의 환을 가진 사이클로알킬(임의로 C_1-4알킬로 치환됨) 또는 페닐이나 나프닐(이 들중 어느것이든 임의로 할로겐, C_1-4알킬, CF₃, C_1-4알콕시, C_1-4알킬 메르캅토, NO₂, 또는 CN으로 치환됨)을 나타내며 또는 R¹²구조식

그룹을 나타내며 여기서 R¹⁵들은 서로 같거나 다르며 수소, C_1-12알킬 또는 C_3-8알케닐(이들중 어느 것이든 임의로 할로겐, C_1-4알킬,CF₃, C_1-4알콕시로 치환됨), 페닐(임의로 할로겐, C_1-4-알킬, CF₃, C_1-4-알콕시, C_1-4알킬 메르캅토 또는 NO₂로 치환), 탄소수 5 또는 6의 환을 가진 사이클로 알킬 또는 -SO₂-R의 설포닐 그룹을 나탸내며 여기서 R⁸은 C_1-12알킬(임의로 염소나 불소에 의해 치환됨) 페닐(임의로 염소, C_1-4알킬, C_1-4알콕시, CF₃또는 NO₂치환됨) 또는 2급 아민그룹을 나타내며 또는 R¹²구조식

의 그룹을 나타내며 여기서 R⁵와 R⁶는 서로 같거나 다른 기로서 수소, C_1-4알킬(이것은 임의로, 할로겐이나, C_1-4알킬로 임의 치환된 페닐에 의해 치환될 수 있다), 페닐(임의로 할로겐, NO₂, C_1-4알킬, C_1-4알콕시 또는 CF₃에 의해 치환됨) 또는 구조식

의 그룹을 나타내며 여기서 R⁷은 수소, C_1-4킬킬 또는 C_2-8알케닐[이들중 어느것이든 할로겐, 니트로, C_1-4알킬 메르캅토, 페닐메르캅토(임의로 할로겐 또는 C_1-4알킬로 치환됨), 페닐(임의로 할로겐 또는 C_1-4알킬로 치환됨) 또는 탄소수 5 또는 6의 환을 가진 사이클로알킬에 의해 치환될 수 있다.]C _1-4 -alkynyl (optionally substituted with tenyl, cyclohexyl or cyclopentyl), C _4-2 -cycloalkyl (optionally substituted with C _1-4 -alkyl or CF ₃ ) or aryl preferably phenyl, or naph As til they are C _1-4 alkyl, C _1-4 -halogeno alkyl, halogen, C _1-4 alkoxy, acetyl, aryloxy or aryl mercapto (halogen, C _1-4 -alkyl, CF ₃ , C _{1- 4} alkoxy or C _1-4 alkyl mercapto), C _1-4 -alkylmer capto, C _1-4 -alkylsulfonyl, alkoxy carbonyl, aminocarbonyl, CN, NO ₂ , 5- or 6-membered heterocycles containing mono-C _1-4 -alkylamino, di (C _1-4 alkyl) amino, C _1-4 -halogenoalkyl mercapto or S, O or N heteroatoms Or R ¹¹ and R ¹² together with the N atom to which they are attached form a heterocycle containing one or more heteroatoms such as O, S and N, or R ¹¹ is OH, C _1-4 -alkoxy (Optionally substituted with phenyl) The formula

R ¹³ represents hydrogen, C _1-12 alkyl, or C _2-8 alkenyl [these are optionally halogen, C _1-4 -alkoxy, phenoxy (which is optionally optionally halogen, methyl or NO ₂ Substitution), C _1-4 alkyl mercapto, phenylmercapto (which is optionally substituted with halogen or methyl), or phenyl (which is optionally substituted with halogen or C _1-4 alkyl) C _1-4 alkynyl, cycloalkyl having 3 to 8 carbon atoms, phenyl or naphthyl (both of which are optionally halogen, C _1-4 alkoxy, C _1-4 alkyl, CF ₃ or NO ₂ ) Or a 5- or 6-membered heterocycle containing a hetero atom such as O, S or N. [R ¹⁴ is a structural formula

Wherein R ¹⁴ is C _1-12 alkyl, C _3-12 alkenyl or C _3-12 akynyl], each of which is optionally halogen, alkoxy, phenyl (which itself is optionally halogen or C _1-4 kilky) ) May be substituted with cycloalkyl having a ring of 5 or 6 carbon atoms containing O, S or N. Cycloalkyl having a ring of 5 or 6 carbon atoms (optionally substituted with C _1-4 alkyl) or phenyl or naphthyl (any of which is optionally halogen, C _1-4 alkyl, CF ₃ , C _1-4 alkoxy, Substituted with C _1-4 alkyl mercapto, NO ₂ , or CN) or R ¹²

Wherein R ^{15 is} the same as or different from each other and is hydrogen, C _1-12 alkyl or C _3-8 alkenyl (any of which is optionally substituted with halogen, C _1-4 alkyl, CF ₃ , C _1-4 alkoxy) Phenyl (optionally substituted with halogen, C _1-4 -alkyl, CF ₃ , C _1-4 -alkoxy, C _1-4 alkyl mercapto or NO ₂ ), cycloalkyl having a ring of 5 or 6 carbon atoms, or Represents a sulfonyl group of -SO ₂ -R, wherein R ⁸ is C _1-12 alkyl (optionally substituted by chlorine or fluorine) phenyl (optionally chlorine, C _1-4 alkyl, C _1-4 alkoxy, CF ₃ Or NO ₂ substituted) or a secondary amine group or R ¹²

Wherein R ⁵ and R ⁶ are the same or different groups as hydrogen, C _1-4 alkyl (which may be optionally substituted by phenyl optionally substituted with halogen or C _1-4 alkyl), phenyl (Optionally substituted by halogen, NO ₂ , C _1-4 alkyl, C _1-4 alkoxy or CF ₃ ) or structural formula

Wherein R ⁷ represents hydrogen, C _1-4 kiloalkyl or C _2-8 alkenyl [any of which is halogen, nitro, C _1-4 alkyl mercapto, phenylmercapto (optionally halogen or C _1-4 Substituted with alkyl), phenyl (optionally substituted with halogen or C _1-4 alkyl) or cycloalkyl having a ring of 5 or 6 carbon atoms.]

의 그룹을 나타내며 여기서 R²⁷부위는 서로 같거나 다르며 수소, C₁-₁₂알킬 또는 C_1-4알케닐(이들중 어느것이든 임의로 할로겐, C_1-4알콕시 또는 그 자신이 C_1-4알킬이나 할로겐으로 임의 치환된 페닐에 의해 치환될 수 있다)탄소수 5 또는 6의 환을 가진 사이클로 알킬 또는 페닐(이들은 할로겐, C_1-4알킬, C_1-4알콕시, C_1-4알킬 메르캅토, CF₃또는 NO₂에 의해 치환될 수 있다)을 나타내며 또는 R⁵및/ 또는 R⁶가 -SO₂-R⁸그룹을 나타내고 여기서 R⁸은 상기에서와 같거나 또는 R⁵와 R⁶가 함께 구조식

의 그룹을 나타내면 여기서 R⁹는 서로 같거나 다른 기로서 각각 C_1-12알킬(임의로 OH, C_1-4알콕시, COOH 또는 COO(C_1-4알킬)로 치환된다), 탄소수 5 또는 6의 환을 가진 사이클로알킬 알킬 부위의 탄소수가 1내지 4인 페닐 알킬 또는 나프틸 알킬(페닐 또는 나프틸 부위는 임의로 할로겐, NO₂, C_1-4알킬, 또는 C_1-4알콕시로 치환된다), 페닐 또는 나프틸 (이들중 어느것이든 임의로 OH, 할로겐, NO₂, C_1-4알킬, C_1-4알콕시, C_1-4알킬메르캅토 또는 CF₃으로 치환된다) 또는 복소원자로서 O,S 또는 N을 포함하는 5-또는 6-원 복소환을 나타내거나 또는 두 R⁹가 인접한 탄소원자와 함께 카보사이클릭환 또는 복소환을 형성하며 또는 두 R⁹중 하나가 수소를 나타내거나 또는 R⁵와 R⁶가 인접한 N원자와 함께 O,S 또는 N을 복소원자로서 함유하는 5- 또는 6-원 복소환을 형성할 수 있다.By ₈ alkynyl, cycloalkyl, phenyl or naphthyl (or whichever of them optionally halogen, C _1-4 alkyl, C _{1-4 al} koksi, CF ₃ or NO ₂ with a ring having 3 to 6 - C ₂ substituted), O, S or N to represent a group of 5-or 6-membered heterocyclic ring or a formula -OR ²⁶ or -SR ²⁶ containing heterocyclic atoms, where R ²⁶ is C ₁ - ₁₂ alkyl, C ₃ - ₁₂ Al alkenyl or C ₃ - ₁₂ alkenyl group [which of these whatever may be optionally substituted with halogen, C _1-4 alkoxy, phenyl (which is a halogen or alkyl, can be substituted by cyclohexyl, putil, thienyl or pyridyl ], C ₃ - ₆ cycloalkyl, or phenyl or naphthyl group represents an (optionally halogen, or whichever of the C _1-4 alkyl, C _1-4 which may be substituted with alkoxy or a nitro group), or R ⁷ is

Denotes a group wherein the R portion ²⁷ is different from or equal to each other hydrogen, C ₁ - ₁₂ alkyl, or C _1-4 alkenyl or (whichever of those optionally halogen, C _1-4 alkoxy or C _1-4 alkyl or they are May be substituted by phenyl optionally substituted with halogen; cycloalkyl or phenyl having a ring of 5 or 6 carbon atoms (these are halogen, C _1-4 alkyl, C _1-4 alkoxy, C _1-4 alkyl mercapto, CF ₃ or NO ₂ ) or R ⁵ and / or R ⁶ represents a -SO ₂ -R ⁸ group wherein R ⁸ is as above or R ⁵ and R ⁶ together

Where R ⁹ is the same or different group as each other C _1-12 alkyl (optionally substituted with OH, C _1-4 alkoxy, COOH or COO (C _1-4 alkyl)), having 5 or 6 carbon atoms Phenyl alkyl or naphthyl alkyl of 1 to 4 carbon atoms of a cycloalkyl alkyl moiety having a ring (the phenyl or naphthyl moiety is optionally substituted with halogen, NO ₂ , C _1-4 alkyl, or C _1-4 alkoxy), Phenyl or naphthyl (any of which is optionally substituted with OH, halogen, NO ₂ , C _1-4 alkyl, C _1-4 alkoxy, C _1-4 alkylmercapto or CF ₃ ) or O, S as a heteroatom Or a 5- or 6-membered heterocycle comprising N or two R ⁹ form a carbocyclic ring or a heterocycle with adjacent carbon atoms or one of the two R ⁹ represents hydrogen or R ⁵ O and R ⁶ together with the N atom is adjacent, S, or a 5-or 6-membered form a heterocyclic ring containing N as a heteroatom Can.

Among the compounds of the formula (I), preferred are as follows.

Compounds of formula (I) wherein X, Y and Z each independently represent a halogen (especially chlorine or fluorine) or one of the groups -SR ¹ , -OR ² , or -SR ²

Wherein R ₁ is a saturated or unsaturated aliphatic or cycloaliphatic hydrocarbon group, in particular 1 to 12 carbon atoms (optionally C _1-4 -alkoxy, C _1-4 alkylmercapto or aryl, aryloxy or arylkercapto (as aryl group) Is preferably phenyl or naphthyl and optionally substituted with halogen, C _1-4 -alkyl, CF ₃ or C _1-4 alkoxy), or alkoxycarbonyl, aminocarbonyl, in particular having a ring of 5 to 6 carbon atoms An alicyclic group or a heterocycle, especially a 5- or 6-membered heterocyclic group containing O, S or N).

R ² is aryl, in particular phenyl or naphthyl (the aryl group optionally being C _1-4 alkyl, C _1-4 polyfluoroalkyl, in particular CF ₃ , halogen, C _1-4 -alkoxy, or aryloxy or arylmercapto (Aryl group is preferably phenyl or naphthyl optionally substituted with halogen, C _1-4 -alkyl, CF ₃ , C _1-4 -alkoxy, NO ₂ or C _1-4 alkyl mercapto) or C _1-4 Aryl group R ₂ is substituted with -alkyl mercapto, C _1-4 -alkylsulfonyl, alkoxycarbonyl, aminocarbonyl, CN, NO ₂ or especially dialkylamino having from 1 to 4 carbon atoms per alkyl group. It may also contain a fused alicyclic ring or a heterocycle.

Still other preferred compounds of formula (I) are as follows.

In the structural formula

X and Y together represent oxygen, sulfur or = NR ³ group.

Wherein R ³ is hydrogen, OH or C ₁ - ₁₂ - alkyl (the alkyl group is a halogen, OH, C _1-4 - alkoxy, or aryloxy, especially phenoxy (an aryloxy group is C _1-4 - alkyl, such as chlorine or Optionally substituted with halogen), or C _1-4 -alkyl mercapto, benzylmercapto, COOH, CONH ₂ , CONH-alkyl, CON (alkyl) ₂ or CONH-aryl (aryl group is preferably phenyl or naphthyl, Optionally substituted by halogen C _1-4 -alkyl, in particular methyl, trifluoromethyl, C _1-4 alkoxy or nitro) or cycloalkyl having a ring of 5 or 6 carbon atoms (optionally substituted by C _1-4 -alkyl) It is) or O, represents the optionally substituted) by a 5-or 6-membered heterocyclic ring containing S or N, or C ₃ - ₈ - alkenyl group (halogen or C _1-4 - is optionally substituted by alkoxy) , C ₃ - ₁₂ - alkynyl (aryl, especially phenyl), the aryl groups are halogen, C _1-4 - alkyl, trifluoromethyl, C _1-4 - alkoxy, or your Furnace is optionally substituted), or optionally substituted with cycloalkyl having a carbon number of 5 to 6 ring), cycloalkyl having a carbon number of 4 to 8 ring (C _1-4 under-containing alkyl, CF ₃ or a fused phenyl ring, Optionally substituted), aryl (especially optionally substituted phenyl or naphthyl) or a 5- or 6-membered heterocyclic structure containing O, S or N, or R ³ represents an OR ₄ group Indicates.

here

그룹을 나타내며R ⁴ is C _1-4 -alkyl, aralkyl (especially benzyl) or

Represents a group

R ⁷ is hydrogen or C ₁ - ₁₂ - alkyl or C ₂ - ₈ alkenyl (each halogen, especially chlorine, nitro, C _1-4 alkyl or aryl mercapto mercapto, especially phenyl mercapto (aryl mercapto group, a halogen or Optionally substituted with C _1-4 -alkyl), or aryl, in particular phenyl (aryl groups are optionally substituted with halogen or C _1-4 -alkyl) or cycloalkyl having a ring having 5 to 6 carbon atoms ), Or

R ⁷ is C _2-8 -arginyl, cycloalkyl or aryl having 3 to 6 carbon atoms, in particular phenyl or naphthyl (halogen, C _1-4 -alkyl, C _1-4 alkoxy, CF ₃ or NO ₂ Optionally substituted) or a 5- or 6-membered heterocycle containing O, S or N or a structure of -OR ²⁶ or -SR ²⁶

R ²⁷ is C _1-12 -alkyl, C _3-12 -alkynyl or C _3-12 -alkynyl (halogen, C _1-4 -alkoxy or phenyl (optionally substituted with halogen or C _1-4 -alkyl) Or optionally substituted with 5- or 6-membered heterocyclic structures containing cycloalkyl, in particular cyclohexyl, or O, S or N, in particular furyl, thienyl or pyridyl) or C _3-6- Cycloalkyl or aryl, preferably phenyl or naphthyl (optionally substituted with halogen, C _1-4 -alkyl, C _1-4 -alkoxy or nitro) or

그룹을 나타낸다.R ⁷ is

Represents a group.

그룹을 나타낼 수 있다. 여기서 R⁵및 R⁶는 서로 동일하거나 또는 다른 것으로서 각각 수소, C_1-4-카킬(아릴, 특히 페닐에 의하여 임의로 치환되며 아릴 치환체는 임의로 할로겐 또는 C_1-4-알킬, 특히 메틸로 치환된다), 아릴, 특히 페닐(아릴 그룹은 임의로 할로겐, NO₂, C_1-4-알킬, 특히 메틸, C_1-4-알콕시 또는 CF₃로 치환된다) 또는

을 의미한다.Wherein the R ²⁷ moiety can be substituted by hydrogen or C _1-12 -alkyl or C _3-8 -alkenyl (halogen, C _1-4 -alkoxy or aryl, in particular phenyl, respectively) Aryl groups may be optionally substituted with halogen or C _1-4 -alkyl or cycloalkyl or aryl having a ring having 5 to 6 carbon atoms, in particular phenyl (the aryl group being halogen, C _1-4 -alkyl, C _1-4 -alkoxy, C _1-4 -alkylmercapto, CF ₃ or NO ₂ may be optionally substituted). In contrast, R ³

It can represent a group. Wherein R ⁵ and R ⁶ are the same as or different from each other and are each optionally substituted with hydrogen, C _1-4 -cakyl (aryl, in particular phenyl and the aryl substituents are optionally substituted with halogen or C _1-4 -alkyl, especially methyl ), Aryl, in particular phenyl (aryl groups are optionally substituted with halogen, NO ₂ , C _1-4 -alkyl, especially methyl, C _1-4 -alkoxy or CF ₃ ) or

Means.

그룹을 나타낸다.Wherein R ⁷ is as above, or R ⁵ and / or R ⁶ represents a -SO ₂ -R ⁸ group wherein R ⁸ is C _1-12 -alkyl (optionally substituted with halogen, in particular chlorine or fluorine) or Aryl, in particular phenyl (aryl group is optionally substituted with halogen, in particular chlorine, C _1-4 -alkyl, C _1-4 alkoxy, CF ₃ or NO ₂ ) or a secondary amino group, or R ⁵ And R ⁶ together

Represents a group.

Wherein the R ⁹ moieties, if identical or different, each have C _1-12 -alkyl (optionally substituted with OH, C _1-4 -alkoxy, COOH or COO (C _1-4 -alkyl)), a ring having 5 to 6 carbon atoms Cycloalkyl, aralkyl having 1 to 4 carbon atoms in the alkyl moiety, preferably phenyl or naphthyl, optionally substituted with halogen NO ₂ , C _1-4 -alkyl or C _1-4 -alkoxy ), Aryl, in particular phenyl or naphthyl (aryl groups are optionally substituted with OH, halogen, NO ₂ , C _1-4 -alkyl, C _1-4 alkoxy, C _1-4 -alkylmercapto or CF ₃ ) or A 5- or 6-membered heterocyclic structure containing O, S or N or two R ⁹ groups may combine with adjacent carbon atoms to form a carbocyclic ring or heterocycle, or one of R ⁹ groups may represent hydrogen If or

R ⁵ and R ⁶ together with adjacent N atoms form a 5-membered 6-membered heterocyclic structure containing at least one heteroatom such as O, N or S.

Preferred compounds of the structural formula (I) also include the following ones.

Z represents a -OR ¹⁰ or -SR ¹⁰ group, wherein R ¹⁰ is hydrogen, a salt forming ion, where O or a bond between S and R ¹⁰ does not represent a covalent bond, but rather a salt formation, in particular a metal cation or It represents an ammonium cation NR ₄ ^+. Where R represents the above meaning or

래디칼이다) 또는 알콕시 특히 탄소수 1내지 4개의 알콕시, 알콕시 알킬렌-옥시, 알릴옥시, 특히 페녹시 또는 나프톡시(아릴옥시 그룹은 임의적으로 할로겐, C_1-4알킬, CF₃또는 NO₂로 치환된다), 알킬 메르캅토, 특히 탄소수 1내지 4의 알킬메르캅트(임의의 아릴, 특히 페닐로 치환되면 페닐은 C_1-4-알킬 또는 할로겐으로 임의로 치환된다), 또는 아릴메르캅토, 아릴설피닐 또는 아릴설포닐(각각 임의로 C_1-4-알킬 또는 할로겐으로 임의로 치환된다) 또는 알킬설포닐 특히 탄소수 1내지 4의 알킬설포닐, 아실아미노 또는 디아실아미노(아실기는 지방족, 지환족, 아르알리파틱, 방향족 또는 복소환성 카르복실산이거나 또는 탄산 도는 티오탄산 유도체의 기이다), 또는 CN, 카르복실산 에스테르기, 특히 탄소수 5내지 6인 환을 갖는 사이클로알킬, 또는 아릴, 특히 페닐(임의적으로 할로겐, C_1-4-알킬 또는 C_1-4-알콕시로 치환된다) 또는 O,S 또는 N을 함유하는 5원 또는 6원 복소환 구조로 치환 된다)을 나타내거나 또는R ¹⁰ is alkyl or alkenyl, in particular C _1-18 -alkyl and C _3-12 -alkenyl halogen, in particular chlorine, fluorine or bromine, OH or acyloxy, wherein the acyl group is aliphatic, substituted, araliparic or Groups or heterocyclic carboxylic acids of aromatic carboxylic acids, in particular

Radicals) or alkoxy, especially alkoxy, alkoxy alkylene-oxy, allyloxy, especially phenoxy or naphthoxy (aryloxy groups optionally substituted with halogen, C _1-4 alkyl, CF ₃ or NO ₂ ) Alkyl mercapto, in particular alkyl mercaps having 1 to 4 carbon atoms (substituted with any aryl, especially phenyl, the phenyl is optionally substituted with C _1-4 -alkyl or halogen), or arylmercapto, arylsulfinyl Or arylsulfonyl (optionally each optionally substituted with C _1-4 -alkyl or halogen) or alkylsulfonyl, in particular alkylsulfonyl, acylamino or diacylamino having 1 to 4 carbon atoms (acyl groups being aliphatic, cycloaliphatic, arali Particulate, aromatic or heterocyclic carboxylic acid or carbonic acid or thiocarbonate derivative), or CN, cycloalkyl having a carboxylic ester group, in particular a ring having 5 to 6 carbon atoms, or aryl, particularly Phenyl is substituted with the indicated 5-or 6-membered heterocyclic structure containing (optionally halogen, C _1-4 - - alkyl or C _1-4 alkoxy is optionally substituted with) or O, S or N), or

R ¹⁰ is alkynyl, in particular alkynyl having 3 to 12 carbon atoms, cycloalkyl especially cycloalkyl having a ring having 3 to 6 carbon atoms (cycloalkyl groups being optionally substituted with halogen, C _1-4 -alkyl or C _1-4 alkoxy Or aryl, in particular phenyl or naphthyl aryl groups, may optionally be C _1-4 -alkyl, polyhalogeno (C _1-4 -alkyl), especially CF ₃ , halogen, C _{1 -4} -alkoxy, aryloxy or aryl mercapto (particularly phenoxy or halogen, C _1-4 -alkyl, CF ₃ , C _1-4 -alkoxy or phenylmercapto optionally substituted with NO ₂ ) C _1-4 -Alicyclic substituted or fused with alkyl mercapto, C _1-4 alkylsulfonyl, alkoxycarbonyl, aminocarbonyl, CN, NN ₂ or monoalkyl amino or in particular dialkyl amino having 1 to 4 carbon atoms per alkyl moiety It contains a group or a heterocyclic group.

래디칼이다), 알킬메르캅토, 특히 C_1-4-알킬 메르캅토(알킬 메르캅토 그룹은 임의적으로 아릴, 특히 페닐로 치환된다) 또는 아릴 메르캅토, 특히 페닐 메르캅토(아릴 메르캅토는 임의적으로 할로겐 또는 C_1-4-알킬로 치환된다) 또는CN, COOH, COOR, CONH₂,CONH(C_1-4)-알킬), CON(C_1-4-알알), 또는 CONH 아릴(여기서 아릴은 페닐 또는 나프틸(임의로 할로겐, C_1-4-알킬, CF₃, C_1-4-알콕시 또는 NO₂로 치환된다)를 나타내는 것이 바람직하다), 또는 특히 탄소수 5내지 12인환을 가지는 사이클로알킬, 또는 O,S 또는 N을 함유하는 5원 또는 6원 복소환 구조, 또는 다음 구조식의 그룹으로 치환된다(R¹¹-N′-아실) 여기서 R₁₁은 상술한 바와 같고, 아실은 지방족, 지환족, 아르알리파틱 또는 방향족 카르복실산기 또는 복소환성 카르복실산, 특히

래디칼을 나타낸다.In contrast, Z can represent a S˝-N'-R ¹² group wherein R ¹¹ and R ¹² are the same or different, respectively, in particular alkyl having 1 to 12 carbon atoms, or especially alkenyl having 3 to 8 carbon atoms, optionally Halogen, in particular chlorine, fluorine or bromine, alkoxy, in particular C _1-4 -alkoxy, or aryloxy in particular phenoxy (aryloxy groups are optionally substituted with C _1-4 -alkyl, halogen or C _1-4 -alkoxy) Or acyloxy, wherein the acyloxy group is an aliphatic, cycloaliphatic, araliphalic or aromatic carboxylic acid or a radical, in particular of a heterocyclic carboxylic acid,

Radicals), alkyl mercapto, in particular C _1-4 -alkyl mercapto (alkyl mercapto groups are optionally substituted with aryl, in particular phenyl) or aryl mercapto, in particular phenyl mercapto (aryl mercapto is optionally halogen Or substituted with C _1-4 -alkyl) or CN, COOH, COOR, CONH ₂ , CONH (C _1-4 ) -alkyl), CON (C _1-4 -al), or CONH aryl, where aryl is phenyl Or naphthyl (preferably substituted with halogen, C _1-4 -alkyl, CF ₃ , C _1-4 -alkoxy or NO ₂ ), or especially cycloalkyl having a ring of 5 to 12 carbon atoms, or A 5- or 6-membered heterocyclic structure containing O, S or N, or a group of the following structural formula (R ¹¹ -N'-acyl) where R ₁₁ is as defined above and acyl is aliphatic, alicyclic, Araliphatic or aromatic carboxylic acid groups or heterocyclic carboxylic acids, in particular

Represents a radical.

R ¹¹ and R ¹² represent, in particular, alkynyl having 3 to 12 carbon atoms (optionally substituted with aryl, in particular substituted with phenyl or cycloalkyl, in particular with 5 to 6 ring carbon atoms) or especially rings having 4 to 8 carbon atoms Cycloalkyl having or optionally substituted with C _1-4 -alkyl, CF ₃ , C _1-4 -alkenyl or C _1-4 -alkyl and optionally containing fused aromatic or cycloaliphatic rings Or a heterocyclic structure, in particular a 5- or 6-membered heterocyclic structure containing S, O or N, and may be optionally substituted if it can contain a fused alicyclic ring or an aromatic ring or an additional heterocycle.

R ¹¹ or R ¹² is also optionally substituted if it represents aryl, preferably phenyl or naphthyl.

Substituents possible as the aforementioned groups include C _1-4 -alkyl, C _1-4 -halogenoalkyl, in particular CF ₃ , halogen, C _1-4 -alkoxy and halogenated alkoxy, acetyl or aryl having 1 to 4 carbon atoms Oxy or aryl mercapto and the like (aryl is optionally substituted with halogen, C _1-4 -alkyl, CF ₃ , C _1-4 -alkoxy, NO ₂ or C _1-4 -alkyl mercapto, especially as phenyl or naphthyl) Can be.

Other substituents include C _1-4 -alkylmercapto and halogenated alkyl mercaptos of 1 to 4 carbon atoms, C _1-4 -alkyl sulfonyl, alkoxycarbonyl, aminocarbonyl, CN, NO ₂ and each If it is mono alkylamino, dialkylamino, etc. which have 1-4 carbon atoms per alkyl site | part, an aryl group may contain the fused alicyclic ring or heterocycle. R ₁₁ and R ₁₂ together with adjacent N atoms form a 3 to 7 membered heterocycle, and the bicyclic ring may be optionally substituted as long as it may contain a heteroatom which is O, S or N and optionally substituted fused aromatic ring or heterocycle. It may contain.

을 나타낼 수 있다.R ₁₂ is in addition to OH, alkoxy, in particular C _1-4 -alkoxy (alkoxy group is optionally substituted with aryl, in particular optionally substituted phenyl), or acyl group

Can be represented.

R ₁₃ is hydrogen or alkyl, in particular C _1-12 -alkyl, or alkenyl, in particular C _2-8 -alkenyl [each optionally halogen, C _1-4 alkoxy, azoleoxy (particularly optionally halogen, methyl or NO ₂₎ Phenoxy), alkyl mercapto, in particular C _1-4 -alkyl mercapto, aryl mercapto (especially phenyl mercapto optionally substituted with halogen or methyl) or aryl (especially substituted with halogen or alkyl) Phenyl)], alkynyl, in particular C _2-8 -alkynyl, in particular cycloalkyl, aryl having a ring having 3 to 6 carbon atoms, in particular phenyl or naphthyl (aryl groups are optionally halogen, C _1-4 -alkoxy, C _1-4 - alkyl, CF _3, is replaced by a NO _2), or a bicyclic heterocyclic structure, especially a 5-or 6-wonbok recalled structure O, S or N-containing, or optionally cycloaliphatic cycloalkyl ahromi ticks, or fusion It may contain a heterocyclic group.

R ¹² may represent a carboxylic ester group.

In the structural formula

R ₁₄ is the same as above

R ₁₂ represents a carboxylic acid amide group of the following structural formula

In the structural formula

R ¹⁵ is as above. here

R ⁸ is as above. or

R ¹² may represent an R ⁵ -N′-R ⁶ group.

In the structural formula

R ⁵ and R ⁶ are as described above.

When X and Y represent = NR ³ , R ³ , they combine with Z and adjacent carbon atoms to form a heterocyclic structure, one of the following structural formulas.

In the above structural formula

R ¹⁶ moieties are the same or different, hydrogen, C _1-4 -alkyl,

C _1-4 -halogenoalkyl (especially C1 or Br as halogen)

C _1-4 -alkoxy or aryloxy, especially phenoxy, in which the aryl group is optionally substituted with halogen, C _1-4 -alkyl, C _1-4 alkoxy or NO ₂

Q represents an O, S or -N'-R ¹⁸ group.

In the structural formula

R ¹⁸ is hydrogen, C _1-6 - appear to produce (phenyl substituted with alkyl or NO _2, especially optionally C1, C _1-4 - - alkoxy, C _1-4) alkyl, cycloalkyl, benzyl or aryl.

R ¹⁹ is hydrogen or alkyl, in particular C _1-12 alkyl [alkyl is optionally C _1-4 -alkoxy, aryloxy (especially phenoxy optionally substituted with methyl or halogen), C _1-4 -alkyl mercapto, Aryl mercapto (especially phenyl mercapto optionally substituted with methyl or halogen) or aryl (especially phenyl or naphthyl optionally substituted with C _1-4 -alkyl, C _1-4 -alkoxy or halogen)] Cycloalkyl having a ring represented or especially having from 5 to 6 carbon atoms (cycloalkyl group optionally substituted with C _1-4 -alkyl or halogen), aryl especially phenyl or naphthyl (aryl group optionally being C _1-4 -alkoxy , Substituted with C _1-4 -alkylmercapto or NO ₂ , a heterocyclic structure, in particular an alicyclic, cycloaromatic or heterocyclic group containing or optionally fused O, S or N (particularly may be optionally substituted with halogen) 5 elements containing 6-membered heterocyclic structure, alkoxy, in particular C _1-4 -alkoxy, allyloxy, in particular phenoxy (aryloxy groups are optionally halogen, C _1-4 -alkyl, CF ₃ , C _1-4 -alkoxy, C _{1 -4} -alkyl mercapto, C _1-4 -alkylsulfonyl, NO ₂ , CN, COO (C _1-4 -alkyl), CONH ₂ or N (C _1-4 -alkyl) is substituted), alkylmer Capto, in particular C _1-12 -alkylmercapto (substituted with C _1-4 -alkoxy, cycloalkyl, in particular cyclohexyl, or aryl in particular chlorine, nitro methoxy or optionally substituted), or amino (optionally) C _1-12 -alkyl, cycloalkyl, aralkyl, or aryl, in particular benzyl or phenyl (optionally substituted with halogen, aryl, CF ₃ , NO ₂ or C _1-4 -alkyl merkito), or optionally two Rings, preferably aromatic rings, are fused onto the aforementioned heterocyclic structures.

P represents O or S

Z represents an azide group.

X, Y and Z represent nitrile groups with adjacent carbon atoms.

Preferred compounds of the formula (I) are as follows.

X and Y represent = N-aryl,

Z is a halogen, alkoxy, alkyl mercapto, aryloxy, aryl mercapto, -NH-aryl radical or R ¹¹ -N'-R ¹² radical. Wherein R ¹¹ and R ¹² are the same as or different as described above.

Particular preference is given to compounds in which X, Y and Z independently represent fluorine, chlorine, optionally phenoxy, or mercapto.

The following compounds are also particularly preferred.

X and Y represent oxygen

Z represents OH, N ₃ or OR ¹⁰ .

기를 나타낸다.R ¹⁰ represents alkyl having 1 to 12 carbon atoms (optionally substituted with chlorine, OH, CN, C _1-4 -alkoxy, C _1-2 -alkyleneoxy or phenyl) or cyclohexyl or alkenyl or 3 Alkynyl, a carbon atom. Or Z is

Group.

R ¹¹ and R ¹² are independently hydrogen, C _1-12 -alkyl (optionally substituted with CN, OH, CONH ₂ , COOH, phenyl, or N-4, 5-dichloroimidazole-2-carboxamide) , Cyclohexyl, alkenyl or alkynyl or aryl having 3 to 6 carbon atoms, in particular optionally substituted phenyl or naphthyl [possible substituents are C _1-4 -alkyl, C _1-4 -halogenoalkyl, especially CF ₃ , Halogen, C _1-4 -alkoxy, and C _1-4 -halogeno alkoxy, acetyl or aryl mercapto, in particular aryl is phenyl or naphthyl (optionally halogen, C _1-4 -alkyl, CF ₃ , C _{1 -4} -alkoxy, NO _{2 or} C _1-4 -alkyl mercapto); and other substituents include C _1-4 -alkylmercapto and C _1-4 -alkylsulfonyl, alkoxycarbonyl , Aminocarbonyl, CN, NO ₂ and in particular monoalkylamino and dialkylamino having 1 to 4 carbon atoms in each alkyl group; The aryl group may contain a fused alicyclic ring heterocycle.], Or R ¹¹ and R ¹² together with adjacent nitrogen atoms form a 5- to 7-membered heterocycle optionally containing N or O atoms.

래디칼을 나타낸다.R ¹¹ and R ¹² are CHO or

Represents a radical.

기를 나타낼 수 있다.Wherein R ¹⁴ represents C _1-4 -alkyl or

Can be represented.

기를 나타낸다.The R ₁₅ moieties independently of each other represent hydrogen, C _1-4 -alkyl or phenyl, or

Group.

기를 형성한다.R ⁵ and R ⁶ are each independently hydrogen phenyl COCCI ₃ or COOC ₂ H ₅ or an adjacent nitrogen atom

Form a group.

The R ⁹ moieties independently represent phenyl, each substituted by hydrogen, C _1-4 -alkyl or optionally OH.

Another preferred compound is as follows.

X and Y are oxygen,

Z represents SR ¹⁰ ,

(R ¹⁰ represents C _1-4 -alkyl, in particular methyl.)

Further preferred compounds are as follows.

X and Y represent sulfur

Z represents methylmercapto and amino

X and Y represent = NR ³ group,

R ³ represents hydrogen, OH, C _1-4 -Dalkyl, benzoyloxy or pyridyl or aryl, in particular phenyl or naphthyl, which may be optionally substituted.

[Possible substituents include C _1-4 -alkyl, C _1-4 -halogenoalcals, in particular CF ₃ , halogen, C _1-4 -alkoxy and C _1-4 -halogenoalkoxy, acetyl or aryloxy or aryl mer Preferred as capto are aryl or phenyl or naphthyl (optionally substituted with halogen, C _1-4 -alkyl, CF ₃ , C _1-4 -alkoxy, NO ₂ or C _1-4 -alkylmercapto), and the like. . Substituents other than C _1-4 -alkyl mercapto, C _1-4 -halogeno alkyl mercapto, C _1-4 -alkyl sulfonyl, alkoxy carbonyl, aminocarbonyl, CN, NO ₂ , and monoalkyl Amino and especially dialkyl amino in which the alkyl group has 1 to 4 carbon atoms.

을 나타낸다.Aryl groups may contain fused alicyclic or heterocycles; and Z is alkoxy, chlorine or arylmercapto, in particular phenylmercapto optionally substituted with C1 or C _1-4 -alkyl, having 1 to 4 carbon atoms Preferably represents or

Indicates.

Wherein R ¹¹ and R ¹² are each independently hydrogen, C _1-4 -alkyl, pyridyl or aryl, in particular phenyl (optionally C _1-4 -alkyl, halogen, C _1-4 -halogenoalkyl, C _1-4 -Alkoxy, C _1-4 -alkyl mercapto, C _1-4 -halogenoalkyl mercapto or halogenoalkoxy).

Preference is given to compounds in which X, Y and Z together with adjacent nitrogen atoms represent oxazole, thiazole, amidazole, oxadiazole, thiadiazole or 1,2,4-triazolone groups. These groups may contain fused benzene rings and are also optionally substituted with amino or alkyl or phenyl or phenoxy (optionally substituted with NO ₂ ), or furyl, or pyridyl or thiazole (optionally substituted with chlorine). Can be.

Furthermore, salts with the following cations are particularly preferred: sodium or NR ₄

Where R is independently of each other hydrogen, 1-4 carbon atoms are alkyl (optionally substituted with hydroxyl)

Or benzyl and two R's combine to form a morpholine ring or three R's combine with each other to form a pyridine ring.

Particular preference is given to compounds of the formula (I) which form groups.

4,5-dichloro imidazole 2-carboxylic acid derivatives of the following structural formulas are also preferred.

In the above structural formula

W represents an O, S or = N-aryl group

When W represents = N-aryl group

Z represents halogen, alkoxy, alkyl mercapto, aryloxy, aryl mercapto, -NH- aryl group or R ¹¹ -N'-R ¹² .

R ¹¹ or R ¹² has the same meaning as it is different.

If W represents O or S

Z represents an -NH- aryl group.

Preparation of 4,5-dichloroimidazole-2-carboxylic acid derivatives according to the present invention uses 4,5-dichloro-2-dichloro methylene imidazole of formula (II) as a starting material and the compound has been described It is not. 4,5-Dichloro-2-dichloromethylene-imidazole (II) is a 2,4,5-trichloro-2-trichloromethyl-2H-imidazole (V) (e.g. of 2-methyl-imidazole Obtained by chlorination) is obtained by heating with a red phosphorus or other reducing agent, for example cuprous chloride.

This process is filed with the German Patent Office.

Keron, which is a dimer of 4,5-dichloroidamidazole-2-carboxylic acid of formula (IV), which can be used as an intermediate, can be obtained by hydrolyzing compound (II) according to the following scheme (a).

Compound (IV) elevates 1: 1 adducts of (b) compound (II) with lower aliphatic carboxylic acid dialkylamides, preferably N, N-dimeltylformamide, having the following fictional structural formula: Obtained by an advantageous method of cleaving at a temperature, preferably 50 ° to 100 ° C. The reaction is preferably carried out in an inert nonpolar solvent such as petroleum ether or carbon tetrahydro chloride.

In this case, it is advantageous to directly cut the addition compound produced in the in situ to generate the compound of formula (IV).

Another method for preparing compound (IV) is prepared by reacting (c) 4,5-dichloro-imidazole-2-carboxylic acid of formula (XI) with an inorganic acid halide, preferably thionyl chloride.

This reaction is preferably carried out in an excess of acid chloride as a solvent at a temperature of 0 ° C. and the boiling point of acid chloride, and compound (IV) is separated by distillation of the excess acid chloride.

X, Y and Z are chlorine or fluorine, and at least one of these radicals represents a compound of formula (I) (formulas IIIa, b, c) which represents fluorine with hydrogen anhydride and / or optionally metal fluoride React with compound (II) or (III). This reaction is carried out in stages:

It is preferable to perform reaction in a hydrocarbon or an excess hydrofluoric acid as a solvent. The reaction temperature is 0 ° C to 200 ° C, preferably 0 ° C to 50 ° C for the compound of formula (IIIa), and 20 ° to 150 ° for the compounds of formulas (IIIb) and (IIIc).

2-trichloromethyl-4,5-dichloro-imidazole (III) may be substituted with an acid binder to prepare a compound of formula (I) wherein X, Y and Z represent -SR ',-OR ² and -SR ² . In presence of phenol, mercaptan or thiophenol.

The reaction process for phenol or methyl mercaptan as a reactant is, for example, as follows.

These reactions are carried out in inert solvents such as hydrocarbons, ethers or ketones. The acid binder used is preferably an alkali metal oxide, hydroxide or carbonate, alkaline earth metal oxide, hydroxide or carbonate, or tertiary amines. However, if alkali metal phenolate, mercaptide or thiophenolate or alkaline earth metal phenolate can be used in the reaction, it can be reacted without further addition of an acid binder. The reaction can also be carried out in the presence of water using an aqueous alkali solution as the acid aqueous solution and can be reacted in a water miscible solvent or a two-phase water insoluble solvent. The reaction temperature can be varied in a wide range, for example -20 ° C to 150 ° C. It is preferable to perform reaction in 0-100 degreeC.

The meanings of R ¹ and R ^{2 in} the structural formulas (IX) and (X) have already been defined above. Particular preference is given to compounds in which R ¹ is methyl and compounds in which R ² is optionally substituted with Cl.

The compound of formula (I) wherein X and Y represent an oxygen atom and Z represents an OH group, namely 4,5-dichloro-imidazole-2-carboxylic acid, is acid hydrolyzed to the compound of formula (II) or (III). Can be prepared.

The reaction proceeds in the following way.

Inorganic acids diluted with water, for example 5 to 90% sulfuric acid or 5 to 35% hydrochloric acid, or organic carboxylic acids or anhydrides thereof containing water as formic acid, acetic acid, hydroxyl or benzoic acid as a reaction medium for supplying water Can be used. When anhydrous organic carboxylic acid is used as the hydrolytic agent, the reaction can be carried out in the presence of a salt of these acids, for example a mixture of acetic acid and sodium acetate.

The reaction is carried out at a temperature between 0 ° and 150 ° C, preferably between 20 ° and 120 ° C.

However, hydrolysis only with water is most convenient. To this end, the compounds of formula (II) or (III) are sufficiently heated to their boiling point until a clear solution is obtained in excess water species. When cooled, the carboxylic acid of structural formula (XI) crystallizes.

The methods used to convert 4,5-dichloro-imidazole-2-carboxylic acids to these salts of formula (XII) or (IIX) are conventional to convert organic carboxylic acids or NH-acid compounds to their salts. React with ammonia or primary, secondary or tertiary amines used. Another method is to react the metal salt of the carboxylic acid with an inorganic salt of the anion which, together with the cation originally bound to the carboxylic acid, forms a poorly soluble salt.

This reaction is preferably carried out in water or alcohol or a mixture thereof. The reaction with ammonia and amine can be carried out in an organic solvent which is inert to the amine.

The amine salts of carboxylic acids are also obtained by reacting compounds of formulas (II) and (III) with at least 3 or quaternary tertiary amines in the presence of water, for example according to the following scheme.

This reaction is carried out at 0 ° to 100 ° C, preferably at 20 ° to 70 ° C. In general, the aminehydrochlorides formed at the same time can be separated because the amine salt of the carboxylic acid is more poorly soluble in water.

Salts of formula (XII) which are primary aliphatic amines can be readily prepared from the compounds of formulas (II) and (III) in the same reactor in the liquid medium. For this purpose the amine / water mixture is first acidified (preferably with hydrochloric acid) and then preferably heated to 80 ° to 110 ° C. together with the compound of formula II or III. The reaction medium is preferably weakly alkaline with bicarbonate to precipitate the desired salt.

Compounds of formula (I), in which X and Y together represent oxygen and Z represents an OR ¹⁰ (formula VI) group, react the compound of formula (II), (III) or (VI) with an appropriate aliphatic or cycloaliphatic alcohol. Manufacture.

R ¹⁰ optionally represents alkyl or cycloalkyl, alkenyl or alkynyl.

When methanol and the compounds of formulas (II) and (III) are used as reactants, the reaction process can be represented by the following method.

As can be seen in the scheme, 2 moles of alcohol are required per mole of compound (II) or (III). The reaction is carried out with an excess of alcohol or an inert solvent such as aliphatic and aromatic hydrocarbons and halogenated hydrocarbons such as benzine, carbon tetrachloride, toluene or chlorobenzene, or ethers such as diethyl ether, dibutyl ether, tetra hydrofuran Or in dioxane. The reaction is carried out over a wide range of temperatures, 0 ° to 120 ° C., preferably 15 ° to 100 ° C. In general, the reaction product is liberated by removing excess solvent and the alkylchloride formed during the reaction simply by distillation.

Acid binders such as alkali metal oxides, hydroxides and carbonates, alkaline earth metal oxides, hydroxides and carbonates and tertiary amines can be added to the stoichiometric amount to bind the hydrogen chloride released during the reaction.

When ketone, a dimer of glycol and the compound of formula (VI), is used as a starting material, the reaction is as follows.

The reaction of the ketone, the dimer of Structural Formula (VI), with an alcoholic reactive statement is carried out in an inert solvent such as aliphatic and aromatic hydrocarbons, halogenated hydrocarbons, ring-opening and cyclic ethers, ketones, dimethylformamide or dimeltylsulfo oxide, or Alternatively, alcohol used as a reactant may be used as a solvent. To be fully converted, at least 2 moles of alcohol are required per mole of compound (VI). The reaction temperature is from 0 ° to 200 ° C., preferably from 15 ° C. to the boiling point of the solvent or alcohol used.

In this case, the R ¹⁰ groups in the formula (VI) are as follows:

Alkyl, hydroxyl, acyloxy (acyl is aliphatic, cycloaliphatic, araliphatic, aromatic or heterocyclic carboxylic acids, among others which may be substituted by alkyl or halogen, in particular chlorine and bromine, having 1 to 18 carbon atoms) In particular, the following group is shown.

Alkoxy (C ₁ -C ₄ ), alkoxyalkyleneoxy (particularly having a C ₂ chain between oxygen atoms), aryloxy (optionally substituted with halogen, methyl or nitro), alkyl mercapto (C ₁ -C ₄ ), Benzyl mercapto (optionally substituted in the aryl group by chlorine), aryl mercapto in particular phenylmercapto (optionally substituted in the phenyl group by chlorine or methyl), acylamino (acyl is aliphatic, araliphatic alicyclic, aromatic Or heterocyclic carboxylic acids, in particular, the following groups),

CN, carboxylic ester group, cycloalkyl having a ring of 5 to 6 carbon atoms, aryl in particular N, O or S as phenyl or naphthyl or a hetero atom optionally substituted by C1, OH ₃ or C _1-4 -alkoxy Cycloalkyl with a 5- or 6-ring containing, optionally substituted with C _1-4 -alkyl or may contain a fused ring.

Carboxylic acid esters of the compounds of formula (VI) with tertiary alcohols, for example, in the presence of a solvent such as dioxane, where appropriate, under catalysts such as sulfuric acid, strong acids such as perchloric acid, and bronfluoride etherates From carboxylic acids and alkenes of formula (XI), in particular isobutylene or iso amylene.

See: Dioxane (“Houben-Weyl”, 4th dedition, 1952, voume Ⅷ, page 534 and “Methodieum Chimicum”, 1975, volume V, page 652).

The process used to prepare the compound of formula (I) wherein X and Y are oxygen atoms and Z is OR ¹⁰ (formula (VI)), wherein R ¹⁰ represents optionally substituted aryl, is as follows.

(a) The compound of formula (II) or (III) is reacted with at least one equivalent of phenol in the presence of at least two or three molar equivalents of an acid binder and water. If phenol is used as the reactant, the reaction is

The reaction can be carried out in water as the reaction medium, in an alcohol such as methanol or ethanol, a ketone such as acetone, or in a water miscible solvent such as an ether such as tetrahydrofuran or dioxane, or an aliphatic or aromatic hydrocarbon or halogenation. It can be performed in a two-phase solvent system using the hydrocarbon as a solvent. As can be seen in the scheme, at least one or two moles of water and two or three moles of acid binder are required. It is preferable to use alkali metal hydroxides and carbonates and alkaline earth metal hydroxides and carbonates as acid binders. The reaction temperature varies between -10 ° and 100 ° C., preferably between 50 ° and 60 ° C. (b) 2-triaryloxymethyl-4,5-dichloro-imidazole of formula (VIII) is partially saponified under basic medium. In the preparation of phenyl ester, the following reaction procedure is used.

The reaction is carried out in the presence of at least 1 molar water and at least 2 molar equivalents of strong bases, preferably alkali metal hydroxides or carbonates and alkaline earth metal hydroxides or carbonates, and water-miscible solvents such as alcohols, acetone, dioxane and tetrahydrofuran At the same time as a solubilizer.

The reaction temperature is between 0 ° and 100 ° C and preferably between 15 ° and 75 ° C.

In this case R ¹⁰ is optionally halogen, alkyl (C ₁ -C ₄ ), CF ₃ , alkoxy (C ₁ -C ₄ ), alkylmercapto (C ₁ -C ₄ ), alkylsulfonyl (C ₁ -C ₄ ), Alkoxycarbonyl, cyano or nitro substituted phenyl or naphthyl.

Particular preference is given to compounds in which R ¹⁰ is phenyl or nitrophenyl.

The compound of formula (I) wherein X and Y represent an oxygen atom and Z represents an SR ¹⁰ (formula) group is required as 4,5-dichloro-imidazole-2-thiocarboxamide (VIIVIII) (starting material). The preparation of 4,5-dichloro-imidazole-thiocarboxamide has been described), which is prepared by the conversion of an alkylating agent to a salt of the corresponding imino-thioether followed by hydrolysis in neutral or acidic medium. When methyl iodide is used as the reactant, for example, the reaction takes the following steps.

Alkylating agents used include alkyl halides, dialkyl sulfates, alkyl sulfonic acid esters and materials that can be used conventionally for this purpose. The first reaction step is carried out in a solvent which is usually anhydrous.

Aromatic hydrocarbons, nitromethane, alcohols, ketones, ring-opening and cyclic ethers are particularly suitable. The reaction temperature is between 0 ° and 120 ° C., preferably between 20 ° and 100 ° C.

The second step of the reaction is preferably reacted using at least the same amount of water and an excess of water as the reaction medium, and the inorganic acid may be added until the pH value of 1 is reached. Addition of solvents that can be mixed with water is possible but usually not necessary.

In formula (I), R ¹⁰ is an alkyl group having 1 to 12 carbon atoms, hydroxyl, (C ₁ -C ₄ ) -alkoxy, (C ₁ -C ₄ ) -alkylmercapto, cyano, carboxylic acid ester, carbo An alkyl group which may be substituted with voxamide and phenyl, an alkyl group optionally substituted with chlorine, nitro, methoxy or methyl, or an alkenyl group or an alkynyl group having 3 to 12 carbon atoms.

However, particular preference is given to compounds in which R ¹⁰ is methyl. The process used to prepare the compound of formula (I) wherein X and Y together represent an oxygen atom and Z represents an optionally substituted amino group (structure VIII)

(a) The compounds of formulas (II) and (III) are reacted with hydrohalides of primary or secondary amines and the resulting imide-chloride type compounds are hydrolyzed.

The reaction using dimeltylamine hydrochlorine is as follows.

The first step of the reaction is carried out in an aprotic solvent. Cyclic ethers such as tetrahydrofuran and dioxane are particularly suitable solvents. The reaction temperature is 50 ° to 200 ° C, and 70 ° to 120 ° C is preferred. Subsequent hydrolysis reactions can be carried out by reacting with water with or without freeing the intermediate in advance. The free hydrogen chloride need not be bound and the presence of an equivalent acid binder, such as an alkali metal oxide, hydroxide or carbonate or alkaline earth metal oxide, hydroxide or carbonate or tertiary amine, for neutralizing this compound is not harmful. The hydrolysis reaction is from 0 ° to 100 ° C, preferably from 10 ° to 70 ° C.

In order to produce 4,5-dichloro-imidazole-2-carboxylic acid amide of highly steric hindrance, for example diisopropylamine, the first step of the reaction is to use the freeamine itself instead of hydrohalide. React.

The reaction process involves at least 2 molar amounts of the compound of formula (II) or (III) having high steric hindrance in an inert solvent such as hydrocarbon, chlorinated hydrocarbon, ring-opened or cyclic ether or ketone or in lower alcohol. At least one mole of secondary amine to which an acid binder such as a higher amine or at least equimolar amount of alkali metal carbonate or alkaline earth metal carbonate or tertiary amine is added, and preferably at a temperature of -10 ° to 120 ° C, preferably 0 ° to 75 ° C. After the reaction is carried out in the solvent, the solvent is removed, and at least an equimolar amount of mole and optionally the inorganic or organic acid binder required for neutralization are added to the reaction mole.

It is preferable to make it react at 90 degreeC or more in reaction with aromatic amine. The reaction process can be expressed as follows.

The reaction can be carried out using a suitable diluent. The reaction is preferably carried out at least in the presence of 1 mole of salt ginseng per mole of aniline. The reaction temperature varies in a relatively wide range but is preferably at least 90 ° C, preferably between 90 ° and 150 ° C. The reaction can be carried out under normal pressure as well as under pressure.

Furthermore, the compound of formula (XVII) is obtained by proceeding to a reactor containing an amine and subsequently separating the imide-chloride of formula (XIV) as an intermediate by two stages of hydrolysis.

If 4,5-dichloroimidazole-2-carboxylic acid N- (2,6-dichlorophenyl) -imide-chloride is hydrolyzed only as an imide-chloride of formula (XIV), the reaction proceeds as follows. Can be represented as:

Concentrated sulfuric acid is preferred as the hydrolysis agent, but can be hydrolyzed with other conventional hydrolytic agents such as formic acid or concentrated acid. The reaction temperature varies in a relatively wide range and generally proceeds at room temperature.

The reaction can be carried out under normal pressure as well as under pressure.

The imide-chloride of formula (XIV) is obtained by reacting 4,5-dchloro-2-dichloromethylene-imidazole of formula (II) with an equivalent amount of amine of formula (XV) at a temperature below about 90 ° C. do. When using 4,5-dichloro-2-dichloromethyleneimidazole of formula (II) and an equivalent molar amount of amine of formula (XV), for example, 2,6-dichloroaniline, the reaction is carried out at a reaction temperature of 90 ° C. or lower. The process can be represented by the following scheme.

The reaction can be carried out using a suitable diluent. Preferred diluent is water. The reaction can be carried out in the presence of at least one mole of hydrochloric acid per mole of aniline. The reaction temperature varies in a relatively wide range, but is generally 90 ° C. or lower, preferably 40 ° C. to 70 ° C. The reaction can be carried out under pressure as well as normal pressure. The imide-chloride of formula (XIV) obtained from this reaction can be used as starting material for the preparation of other compounds of the present destruction.

(b) In addition, the compound of formula (XVII) is obtained by deacylating 4,5-dichloro-imidazole-2-carboxylic acid N-formylamide of formula (XIX).

The reaction with 4,5-dichloro-imidazole-2-carboxylic acid N-formyl-isopropylamide is for example as follows.

Modified inorganic acids or organic carboxylic acids such as formic acid or oxalic acid, or concentrated inorganic acids such as, for example, dark sulfur phase, are used as hydrolysing agents.

The reaction temperature is from 10 ° C. to 150 ° C., preferably from 20 ° C. to 100 ° C. depending on the hydrolysis agent.

4,5-Dichloro-imidazole-2-carboxylic acid-N-formyl-amide (formula (XIX)) required as a precursor is obtained by reacting a compound of formula (II) with at least 2 moles of formic acid amide. It is preferable.

This reaction can be carried out in the presence of a solvent or without a solvent. Examples of solvents that may be used include aliphatic and aromatic hydrocarbons and halogenated hydrocarbons, ring-opening and cyclic ethers or aliphatic nitriles such as, for example, acetonitrile and the like, and water may also be used. The reaction temperature is -10 ° to 110 ° C when reacted under anhydrous conditions. If water is present, the reaction temperature is between -10 ° and + 10 ° C.

The reaction of compound (II) with N-isopropyl-formamide is as follows, for example.

For this reaction the compound of formula (II) is obtained directly at a reaction temperature of 50 ° to 150 ° C., preferably at 80 ° to 120 ° C. when at least 1 mole of water is added per mole.

The 4,5-dichloro-imidazole-2-carboxylic acid N-acylamide of the structural formula (XXI) in which the α-carbon atom phase of the acyl group does not contain a hydrogen atom may be prepared by a similar method.

The first step of the reaction is carried out in the same solvent and at the same concentration as indicated above. The second reaction step adds at least equimolar amounts of water to a non-free intermediate product at a temperature between 0 ° and 100 ° C., preferably between 10 ° and 50 ° C.

R ¹³ in formula (XXI) is a CO-carbon bonded radical containing no hydrogen atoms on the α-carbon atom and in particular a tertiary alkyl group having 4 to 12 carbon atoms and an α-alkyl-substituted vinyl group having 3 to 8 carbon atoms. , An alkynyl group having 2 to 8 carbon atoms, an α-substituted cycloalkyl group having a ring having 3 to 6 carbon atoms, and also an aryl group, especially optionally halogen, alkyl (C ₁ -C ₄ ), 0-alkyl (C _1- C ₄ ), CF ₃ , or 5- or representing phenyl or naphthyl substituted with NO ₂ or containing a carbocycle ring or other heterocycle containing or fused with oxygen, sulfur and / or nitrogen in the ring; A six-membered heterocyclic group is shown.

(c) The compound of formula (XVII) is a structural formula obtained from aliphatic, araliphatic or cycloaliphatic carboxylic acid amides containing at least one hydrogen atom in the carbon atom at the α-position of the compound of formula (II) and the carbonyl group Obtained by hydrolysis of the product of (XXIII).

R ²⁰ and R ²¹ in formula (XXII) each represent hydrogen, an alkyl group (C ₁ -C ₄ ) or an aryl group, or R ²⁰ and R ²¹ represent a tetramethylene or pentamethylene group. It can be prepared by a simple method of reacting a compound with a carboxylic acid amide.

Suitable carboxylic acid amides are all substances derived from primary amines and especially aliphatic, araliphatic, cycloaliphatic and aromatic amines. The carboxylic acid couple of these carboxylic acid amides should contain at least one hydrogen atom on the carbon atom in the α-position relative to the carbonyl group. Thus, for example, suitable reactants are amides of acetic acid, propionic acid, butyric acid, isobutyric acid, phenylacetic acid and cyclohexane, carboxylic acid.

At least equimolar amounts of reactants are used but carboxylic acid amides may be used in excess as the reaction medium. The reaction can be carried out in an inert diluent, but is preferably carried out without solvent. The reaction temperature is 0 ° to 150 ° C and 20 ° to 100 ° C is preferred.

This reaction can be carried out using a compound in which a carboxylic acid group and an amine group are bound together in a ring form, that is, a lactam.

In this case, 4,5-dichloro-imidazole-2-carboxylic acid amide of the formula (XXIV) in which the alkyl group of the amide group is substituted by the carboxyl group is obtained by hydrolyzing the intermediate (XXIII).

N is 3, 4 or 5 in the above formula.

Examples of lactams that may be used include pyrrolidone, valerolactam and caprolactam. Corresponding reaction conditions are described above. (d) The compound of formula (XVII) can be obtained by cleaving the 4,5-dichloro-idamizol-2-oil-urea of formula (XXVI). Cleavage is carried out by the action and hydrolysis of the salt.

For example, using 4,5-dichloro-amidazoloyl-1,3-dimethyl-urea, the reaction follows the following procedure.

The cleavage by the action of heat is carried out in the absence of a diluent to melt or in a high melting point solvent such as chlorobenzene, mesitylene or tetralin. The reaction temperature is between 100 ° and 250 ° C.

The hydrolysis reaction is carried out with concentrated inorganic acids, for example concentrated sulfuric acid or phosphoric acid or concentrated formic acid. The reaction temperature is between 50 ° and 150 ° C.

The 4,5-dichloro-imidazole-urea corresponding to the structural formula (XXV) or (XXVI) required as a precursor is a mono- or 1,3-disubstituted urea or a compound of formulas (II) and (III), respectively Obtained by reaction with urea. For example, the reaction with monosubstituted urea follows this procedure.

The reaction with 1,3-disubstituted urea follows this procedure.

The preparation is prepared by reacting a compound of formula (II) or (III) with at least two molar amounts of the corresponding urea. This reaction can be carried out without solvent or in an inert organic solvent such as dioxane or water, for example. The reaction temperature is 0 ° to 120 ° C and 20 ° to 100 ° C is preferred.

In the structural formulas (XXVI) and (XXVII), R ¹⁵ has the meaning defined above. Preferably R ¹⁵ is hydrogen or an alkyl group having 1 to 12 carbon atoms or substituted with 0-alkyl (C ₁ -C ₄ ), phenyl (optionally substituted with halogen or C ₁ -C ₄ -alkyl), cyclopentyl or cyclohexyl An alkenyl group having 3 to 8 carbon atoms, or a panyl group (optionally halogen, C ₁ -C ₄ -alkyl, CF ₃ , 0-alkyl and S-alkyl (C ₁ -C ₄ ) or NO ₂ Is substituted).

(e) The compound of formula (XVII) may also be 4,5-dichloro-imidazole-2-thiocarboxylic acid S-alkyl ester (formula VII)) or 4,5-dichloro-imidazole-carboxylic acid aryl ester (Formula (VI)) can be obtained by reacting with ammonia or primary or secondary amines.

The reaction of 4,5-dichloro-imidazole-2-thio-carboxylic acid-S-methylester or 4,5-dichloro-imidazole-2-carboxylic acid phenylester with dimethylamine follows the procedure below. .

The reaction is preferably carried out in a solvent. Suitable solvents are water, alcohols, ring-opened and cyclic ethers, ketones, aliphatic and aromatic hydrocarbons, dimethylformamide, dimethylsulfoxide and the like. Suitable 4,5-dichloro-imidazole-2-thiocarboxylic acid S-alkylesters are alkylesters and benzylesters and suitable 4,5-dichloro-amidazole-carboxylic acid arylesters contain the required arylester groups. It is ester. Since the phenol part of these compounds is removed again, it is preferable to use a phenyl ester which is not substituted.

Primary or secondary amines are used in at least molar amounts, but it is advantageous to add an excess molar amount (eg in the case of volatile amines). The reaction temperature is -20 ° to + 120 ° C and 20 ° to 75 ° C is preferred. The preparation of 4,5-dichloro-imidazole-2-thiocarboxylcarboxylic acid alkyl ester and the preparation of 4,5-dichloro-imidazole-2-carboxylic acid aryl ester have already been described herein. (f) The compound of formula (XVII) can be obtained by reacting a ketone which is a dimer of 4,5-dichloro-imidazole-2-carboxylic acid of formula (IV) with ammonia or a primary or secondary amine.

For example, the reaction of dimethylamine is as follows.

The reaction is preferably carried out in a solvent. Examples of suitable solvents are hydrocarbons, alcohols, ring-opened and cyclic ethers, ketones, dimethylformamide and dimethyl sulfoxide. The reaction temperature is -10 ° to + 150 ° C and the reaction is preferably carried out at 0 ° C to 100 ° C.

R ¹¹ and R ¹² in the formulas (XVIII), (XIX), (XX), (XXI), (XXIJ) and (XXV) are as defined above. Wherein R ¹¹ and R ¹² represent hydrogen or an alkyl group having 1 to 12 carbon atoms or halogen (fluorine, chlorine or bromine), hydroxyl, alkyl (C ₁ -C ₄ ), 0-aryl (optionally C ₁ -C _4- Substituted by alkyl, halogen or C ₁ -C ₄ -alkoxy), S-alkyl (C ₁ -C ₄ ), S-benzyl, S-aryl (optionally substituted by chlorine or methyl with aryl), carboxyl, carboxamide , Cyano, aryl (preferably phenyl and naphthyl optionally substituted with halogen, methyl, CF ₃ , 0-alkyl (C ₁ -C ₄ ) or NO ₂ ) or cycloalkyl (ring having 5 to 6 carbon atoms) Or 3 to 12 representing a 5 or 6 membered heterocycle containing oxygen, sulfur and / or nitrogen as a heteroatom or optionally substituted with (substitutable) phenyl or cycloalkyl (C ₅ -C ₆ ) It indicates the carbon atom design alkynyl, or optionally alkyl (C ₅ -C ₆₎ which may contain an optionally substituted or fused ring carboxylic acid, having 4 It represents a cycloalkyl group having an alicyclic ring, or a 5-angle or 6-angle heterocyclic group which may contain a carboxyl ring or a heterocycle fused by containing oxygen, sulfur and / or nitrogen as a hetero atom. . Or R ¹¹ and R ¹² together with the nitrogen atom to which they are attached may form a ring of three to seven angles in addition to a nitrogen atom which may contain heteroatoms such as oxygen, sulfur or nitrogen and fused carboxyl rings. have.

The preparation of the compounds of the formulas (XXVII) and (XXVIIa) has already been described (of the 4,5-dichloro-imidazole-2-carboxylic acid amides of the formulas (XIX), (XXI), (XXV) and (XXVI) Compared with the recipe).

R ¹³ in the formula represents hydrogen or an optionally substituted organic radical and R ¹⁵ represents alkyl or aryl.

그룹(R¹⁴는 알킬 또는 아릴을 나타낸다)인 화합물은 같은 방법으로 제조할 수 있다. 이목적을 위하여 카르바민산 에스테르를 구조식(Ⅱ) 또는 (Ⅲ)의 화합물과 반응시킨다.R ¹²

Compounds which are a group (R ¹⁴ represents alkyl or aryl) can be prepared in the same manner. For this purpose, the carbamic acid ester is reacted with the compound of formula II or III.

If N-monosubstituted carbamic acid is used, a compound of the amide-chloride type is obtained in the first step and then hydrolyzed.

When N-methyl-carbamic acid phenylester is used as starting material, for example, the reaction proceeds according to the following reaction formula.

The reaction of the first stage is carried out at an temperature between 50 and 150 ° C. in an aprotic solvent, preferably a cyclic ether such as dioxane or tetrahydrofuran. The next second step is done with at least molar amount of water; And diluents such as alcohols, ketones or cyclic ethers may be present.

Hydrogen chloride liberated during the hydrolysis reaction can be bound by addition of a molar amount of base such as alkali metal oxides, hydroxides or carbonates or tertiary amines but this is usually not necessary. The reaction temperature is 0 ° to 100 ° C and 20 ° to 70 ° C is preferred.

When N-substituted carbamic acid esters are used, the reaction process can be controlled such that N- (4,5-dichloro-idamizol-2-yl-carbamic acid ester (XXXI) is formed in the first stage reaction. In this case the second mole of carbamic acid ester is used as a “hydrolysis” agent for intermediates corresponding to formula (XXIX).

When carbamic acid ethyl ester is used as starting material, the reaction proceeds as follows.

According to this scheme, at least 2 moles, preferably 2-3 moles of carbamic acid ester are reacted with the compound of formula II. Preference is given to cyclic esters such as dioxane and tetrahydrofuran as the reaction medium. The reaction temperature is from 20 ° to the boiling point of the solvent.

R ¹¹ has already been defined for the structural formula (XXX). The R ¹⁴ group is an alkynyl, alkoxy (C ₁ -C ₄ ), aryl, preferably phenyl (halogen or C ₁ -C ₄ -alkyl) alkyl group having 1 to 12 carbon atoms or 3 to 12 carbon atoms which may each be substituted with halogen Cycloalkyl group or an allyl group, optionally substituted with halogen, alkyl (C ₁ -C ₄ ), CF ₃ , 0-alkyl (C _1). -C _4), S- alkyl _{(C 1 -C 4), NO} 2 , or cyano, denotes a furnace, optionally substituted phenyl, naphthyl and the like.

The process used to prepare the compound of the formula R ¹¹ is hydrogen and R ¹² is the sulfonyl group SO ₂ -R ⁸ (formula (XXXI) is 4,5-dichloro-2-dichloromethylene-imidazole (II) Is reacted with an alkyl-metal salt of N-substituted sulfonamide R ⁶ -SO ₂ -NH ₂ and water.

The reaction can be carried out either alone or simultaneously with a solvent which can be mixed with water, such as acetone, dioxane or tetrahydrofuran and optionally acid binders such as alkali metal oxides, hydroxides or carbonates, alkaline earth metal oxides, hydroxides or carbonates or tertiary amines. In presence. The reaction temperature is 0 ° to 100 ° C, preferably 20 ° to 100 ° C.

R ⁸ has the meaning described above and preferably represents an alkyl group having 1 to 4 carbon atoms optionally substituted with chlorine or fluorine, or optionally with halogen, methyl, C ₁ -C ₄ -alkoxy, CF ₃ or nitro Substituted phenyl or a secondary aano group.

Several processes showing the preparation of the 4,5-dichloro-imidazole-2-carboxylic acid amide of the formula (XVII) include hydroxyl amino groups (structure (XXXII)) in which X and Y are oxygen atoms and Z is optionally substituted. It can be used to prepare the compound of the structural formula (I) shown. For example, the corresponding process (e) comprises phenylester or S-methylthio-ester of 4,5-dichloro-imidazole-2-carboxylic acid with hydroxylamine or O-alkyl or N, O-di Can be reacted with alkyl derivatives.

For hydroxylamine itself, for example 4,5-dichloro-imidazole-2-hydroxyamic acid is obtained by this method. The reaction conditions are the same as described in process (e) for the corresponding carboxylic acid amide. R ¹¹ and R ²³ in formula (XXXII) preferably represent hydrogen or a lower (C _1-4 ) -alkyl group, benzyl group or cyclohexyl group. The alkyl and aralkyl groups corresponding to R ¹¹ and R ²³ subsequently react 4,5-dichloro-imidazole-2-hydroxyamic acid (R ¹¹ and R ²³ = H) with the alkylating agent, preferably in an alkaline medium. Can be introduced into the molecule.

Several processes for the preparation of 4,5-dichloro-imidazole-2-carboxylic acid amide have been described in which X and Y represent an oxygen atom and Z represents a hydrazino group (formula (XXXIII) optionally substituted) It can be used to prepare the compound of I). Particular preference is given to the process of reacting the 4,5-dichloro-imidazole-2-carboxylic acid alkyl ester with the corresponding hydrazine.

Reaction with 4,5-dichloro-imidazole-2-carboxylic acid methyl ester with unsubstituted hydrazine (as hydrate) affords 4,5-dichloro-imidazole-2-carboxylic acid hydrazine (XXXIIIa). .

The reaction is generally carried out by reacting a 4,5-dichloro-imidazole-2-carboxylic acid alkyl ester in a solvent with at least molar amount of hydrazine or substituted hydrazine. Suitable solvents are aliphatic light aromatic hydrocarbons, ring-opening and cyclic netters, alcohols and the like, and water may also be used. Since hydrazine is a strong base, the reaction product is obtained in the form of a hydrazinium salt (this salt is formed in the acidic ring-nitrogen of the imidazole group) when more than a certain amount of a particular hydrazine is used. Free hydrazine can be obtained by acidifying this salt. The reaction temperature is 0 ° to 120 ° C and 20 ° to 100 ° C is preferred.

R ¹¹ , R ⁵ and R ⁶ in formula (XXXIII) are hydrogen or an alkyl group having 1 to 4 carbon atoms, a benzyl group optionally substituted with halogen or methyl, or optionally halogen, nitro, methyl, alkoxy (C ₁ -C ₄ ) Or a phenyl group substituted with CF ₃ .

R ⁵ and R ⁶ may be bonded to a nitrogen atom bonded thereto and optionally a hetero atom such as oxygen, sulfur or nitrogen to form a five- or six-membered ring.

The carboxylic acid hydrazine of the structural formula (XXXIII) in which at least one of R ⁵ and R ⁶ represents a hydrogen atom can be further reacted according to a known process.

Some possible reactions using 4,5-dichloro-imidazole-2-carboxylic acid as an example are described as follows.

(a ') Preferably react with aldehydes or ketones under acidic catalysts, if appropriate in an organic solvent.

The R ⁹ moiety in formula (XXXIV) is an alkyl group (C ₁ -C ₁₂ ), optionally substituted with OH, O-alkyl (C ₁ -C ₄ ) or COOH or COO-alkyl (C ₁ -C ₄ ), or in a ring Cycloalkyl groups having 5 or 6 carbon atoms, aralkyl groups having 1 to 4 carbon atoms in the alkyl chain and aralkyl groups optionally substituted with aryl groups with halogen, nitro, alkyl (C _1-4 ) or alkoxy (C _1-4 ) Or an aryl group, preferably phenyl or naphthyl, optionally substituted with OH-haloken, nitro, alkyl (C _1-4 ), alkoxy (C _1-4 ), alkyl mercapto (C _1-4 ) or CF ₃ Or a 5- or 6-membered heterocyclic group having oxygen, sulfur or nitrogen in the ring and both R ⁹ groups can form a cyclic, heterocyclic ring.

(b ') Reaction with carboxylic acid chloride in the presence of an acid binder in water or organic solvent or with carboxylic anhydride in the presence of an inert solvent or without an inert solvent.

In formula (XXXV), R ⁷ is hydrogen or an alkyl group having 1 to 12 carbon atoms or optionally phenoxy optionally substituted with haloken, O-alkyl (C _1-4 ), O-aryl, especially haloken, methyl, or Nitro, or S-alkyl (C _1-4 ), S-aryl (optionally substituted with chlorine or methyl), or phenyl (optionally substituted with haloken) or alkyl (C _1-4 ), or 2 Alkyl having from 8 to 8 carbon atoms, cycloalkyl having 3 to 6 ring carbon atoms, an aryl group, haloken, O-alkyl (C _1-4 ), S-alkyl (C _1-4 ), alkyl (C _{1) -4} ), 5- or 6-membered phenyl or naphthyl or ring optionally substituted with CF ₃ or NO ₂ , containing oxygen, sulfur and / or nitrogen and which may contain a carboxyl or addition heterocyclic ring deposited The original heterocyclic group is shown.

It is reacted with the (thi) carboxylic acid ester chloride in the organic solvent in the presence of the (c ′) acid binder.

In formula (XXXVI), R ²⁶ is preferably an alkyl group having 1 to 12 carbon atoms, a 3 to 12 alkenyl group or an alkynyl group having 3 to 12 carbon atoms which may be optionally substituted with halokenes, alkoxy (C ₁ -C ₄ ), Phenyl (optionally substituted with C _1-4 -alkyl or haloken), cyclohexyl, furyl, thienyl or pyridi, or a cycloalkyl or aryl group which is 5 to 6 ring carbon atoms, preferably Phenyl or naphthyl, alkyl (C ₁ -C ₄ ), O-alkyl (C ₁ -C ₄ ) or nitro substituted with haloken.

In the presence of the (d ') acid binder, it is preferably reacted with (thio) carbamic acid chloride in an organic solvent.

Or preferably reacted with isocyanate or isothiocyanate in an organic solvent.

R ²⁷ in the formulas (XXX ') and (XXX') is hydrogen or an alkyl group having 1 to 12 carbon atoms or an alkenyl group having 3 to 8 carbon atoms which may be substituted with haloken, O-alkyl (C ₁ -C ₄ ), or Cycloalkyl groups which represent phenyl (optionally substituted with haloken or alkyl (C ₁ -C ₄ )) or have rings having 5 or 6 carbon atoms or optionally haloken, alkyl (C ₁ -C ₄ ), O-alkyl ( Phenyl group substituted with C ₁ -C ₄ ), S-alkyl (C ₁ -C ₄ ), CF ₃ , or NO ₂ .

(e ′) Preferably, the organic solvent is reacted with sulfonic acid chloride and sulfamic acid chloride in the presence of an acid binder.

In the formula (XXXIX), R ⁸ represents an alkyl group having 1 to 12 carbon atoms and optionally substituted with chlorine or fluorine, or optionally chlorine, alkyl (C ₁ -C ₄ ), O-alkyl (C ₁ -C4) , Phenyl or naphthyl substituted with CF ₃ or NO ₂ , or R ⁸ represents a secondary amino group. The compound of formula (I), wherein X and Y represent an oxygen atom and Z represents an azide group, that is, 4,5-dichloro-imidazole-2-carboxylic acid azide (formula (XL)) is nitrous acid or its lower One of the esters can be prepared by reacting with 4,5-dichloro-imidazole-2-carboxylic acid hydrazide (XXXIII). The reaction process with nitrous acid itself is as follows.

The reaction is carried out in water or lower alcohol at a temperature of -20 ° to + 50 ° C, preferably at 0 ° to 20 ° C.

Alternatively, the (XL) compound can be prepared by reacting 4,5-dichloro-2-dichloromethylene-imidazole (II) with a saline solution of hydrazophosphoric acid.

The reaction can be carried out in water or in a solvent which can be mixed with water, for example dioxane, tetrahydrofuran or acetone. The reaction temperature is between 0 ° and 100 ° C., preferably between 0 ° and 50 ° C.

To prepare a compound of formula (I) wherein X and Y represent sulfur atoms and Z represents a SR ¹⁰ (structure (XLI)) group, compound (II) or (III) is first reacted with a salt of hydrogen sulfide to A salt of 5-dichloro imidazole-2-dithio carboxylic acid (XLII) is obtained and then reacted with an alkylating agent.

R ¹⁰ in the structural formula preferably represents an alkyl group having 1 to 6 carbon atoms, an alkenyl group or alkynyl group having 3 to 5 carbon atoms, a cyclohexyl group or a benzyl group optionally substituted with chlorine or methyl.

When sodium hydrogen sulfite and methyl iodide are used as reactants, for example, the reaction is as follows.

It is preferable to use alkali metal hydrogen sulfide or alkaline earth metal hydrogen sulfide for the first stage of reaction. The solvent used is water or lower alcohols or mixtures thereof. The reaction temperature is -20 ° to 100 ° C and preferably 0 ° to 70 ° C. Salts corresponding to formula (XLII) can be separated by evaporation of the solvent. However, these salts can, in general, be converted to the dithio carboxylic acid esters corresponding to formula (XLI) by reaction with the second stage alkylating agent without purification as described above.

Alkyl halides, alkenyl halides, alkynyl halides, cycloalkyl halides or aralkyl halides or suitable dialkyl sulfates or sulfonic acid alkyl esters are commonly known as the alkylating agents used.

In general, the reaction is carried out first with alkali metal chlorides or alkaline earth metal chlorides formed during the reaction, optionally leading to (XLI), in the same reaction medium from which the salt of the formula (XLII) is produced, preferably in a mixture with lower alcohols or water. Do this after separating and removing. The reaction temperature is from 0 ° to 100 ° C.

In order to prepare a compound of formula (I) wherein X and Y together represent a sulfur atom and Z represents an amino group (structure (XLIII)), 4,5-dichloro-imidazole-2-carboxylic acid natril (L) was prepared. React with hydrogen sulfide.

All processes known in the literature for the conversion of carboxylic acid nitriles to the corresponding thiamides can be used for this purpose. For example, the process involves reacting nitrile (L) with excess hydrogen sulfide in pyridine as a solvent at 20 ° to 50 ° C. in the presence of an equimolar amount of a strong basic amine (eg triethylamine).

A compound of formula (I) wherein X and Y together represent a sulfur atom and Z represents an amino group substituted with Z or an optionally substituted hardrazino group (Formula XLIV) is 4,5-dichloro-amidazole-2-dithio Carboxylic acid esters can be obtained by reacting with primary or secondary amines, hydroxylamines or hydrazines.

In the formula (XLIV), R ¹¹ and R ¹² refer to the groups shown in the case of the formulas (XVII) (XXXII) and (XXXIII). It is preferable to advance reaction using the ratio of equimolar amount. Solvents used are hydrocarbons, alcohols, ring-opening and cyclic esters and water, or water and mixtures of the above-mentioned organic solvents and the like. The reaction temperature is 0 ° to 150 ° C and preferably 15 ° to 100 ° C.

The compound of formula (I), in which X and Y together represent an amino group and Z represents an alkoxy group, is stable in the form of a salt, like conventional imino-carboxylic acid esters. Imino-carboxylic acid ester. The 4,5-dichloro-idamizol-2-imino-carboxylic acid ester (XLV) is used to form an alcohol in the presence of an inorganic acid that is strong against the 4,5-dichloro-idamizol-2-carboxylic acid nitrile of the formula (L). Obtained by reaction.

The alcohols used are saturated or unsaturated aliphatic, cycloaliphatic or araliphatic alcohols and hydrochloric acid, preferably hydrochloric acid, is used as the inorganic acid.

The reaction can be carried out in this solvent with a specific alcohol as a solvent and can be carried out with a stoichiometric amount of alcohol in a solvent such as a hydrocarbon or a ring-opening or cyclic ether. The reaction temperature is -20 ° to 100 ° C, preferably 0 ° C to 50 ° C.

Compounds of formula (I), wherein X and Y represent substituted imino groups, are obtained by reacting the imide-chloride of formula (XIV) with a compound of general structure Z-H.

4,5-Dichloro-imidazole-2-carboxylic acid N- (2,6-dichlorophenyl) -imide-chloride is used as the imide-chloride of formula (XIV) and 4-chloro-thiophenol is formula ZH When used as a compound of half the process is as follows.

The reaction can be carried out using a suitable weighting agent. In particular water can be used as a suitable weighting agent. The reaction can also be carried out in the presence of a suitable acid binder. Examples of acid binders that can be used include alkali metal hydroxides such as sodium hydroxide or potassium hydroxide.

The reaction temperature varies over a wide range and generally the reaction is carried out between 10 ° and 100 ° C.

The reactants are used in equimolar amounts except when the Z-H compound acts simultaneously as an acid binder due to its basicity. In this case, the compound of the structural formula Z-H can be used in excess to react. In general, the reaction is carried out under normal pressure.

A compound of formula (I), wherein X and Y are substituted together and Z represents a monosubstituted imino group (structure (XLIV)), acts as a primary amine on compound (II) or (III) Manufactures:

In the formula (XLVI), R ¹¹ has the meanings defined above but does not represent hydrogen.

During the reaction, 2 moles of hydrogen chloride (from scheme (II)) or 3 moles (from scheme (III)) are produced.

This reaction can be carried out using 4 or 5 moles of amine used in the reaction instead of 2 moles stoichiometrically required. However, corresponding amounts of alkali metal carbonate, alkaline earth metal carbonate or tertiary amine can be used as the acid binder. As a rule, the reaction is carried out in a solvent. Suitable solvents may be hydrocarbons, alcohols, ring-openings and cyclic ethers as well as water. When water and alcohol are used as the solvent, it is desirable to ensure that excess amine is always present during the reaction to avoid side reactions. The reaction temperature is -20 ° to 150 ° C and 0 ° to 100 ° C is preferred.

A compound of formula (I) wherein X and Y represent a hydroxy amino group and Z represents an amino group, namely 4,5-dichloro-imidazole-2-carboxylic acid amide-oxime (formula (XLVII)) is 4, Prepared by addition reaction of hydroxyl amine to 5-dichloro-imidazole-2-carboxynonitrile (L):

This reaction is preferably carried out in water or lower alcohols or in mixtures thereof. Hydroxylamine is used at least in equimolar amounts. The reaction temperature is 0 ° to 100 ° C and preferably 15 ° to 75 ° C.

Derivatives bound to the -NH ₂ or -NOH group of the amidoxime group can be prepared from compound (XLVII). Alkylation, for example, in an alkaline medium produces 0-alkyl-amide-oxime (XLVII) and for example acylation produces O-acyl-amide-oxime (IL) together with carboxylic acid halides or halogeno carboxylic acid derivatives. (IL)

The groups R ⁴ and R ⁷ in the formulas (XLVIII) and (IL) have the meanings given above.

The compound of formula (I) wherein X, Y and Z together represent a nitrogen atom, i.e. 4,5-dichloro-imidazole-2-carboxylic acid nitrile of formula (L), contains at least 3 or 4 moles of ammonia Prepared by acting on the compound of (II) or (III), respectively:

The compound of formula (L) is obtained in high yield without substantial side reactions when ammonia is present in the sulfur phase excess in the reaction. That is, the reaction process of adding the compound of formula (II) or (III) to the already added ammonia is preferable.

Ammonia can itself be used as a solvent, which means that the reaction is carried out in liquid ammonia.

Alternatively, ammonia solutions are used which are mixed with cyclic ethers such as dioxane or tetrahydrofuran or lower alcohols or water, or mixtures thereof. When the reaction is carried out in lower alcohol, water or a mixture thereof, the reaction temperature is preferably -20 ° to + 50 ° C, preferably 0 ° to 25 ° C. The nitrile of formula (L) is obtained in the form of its water-soluble ammonium salt in the process, and can be obtained in the free form of a dichloride salt in sufficient amount by adding an inorganic acid.

Compounds of formula (I) in which two or three of X, Y and Z combine with at least one heteroatom, preferably oxygen, sulfur or nitrogen, to form a five-membered ring, are taken from the related 1,4-position to the acyl group. A reactant containing two hydrogen atoms which may be substituted is prepared by acting on a compound of formula (II) or (III).

Examples of the compound which can be produced by this method include the following.

(a) a compound having a 5-membered ring containing an oxygen atom and a nitrogen atom:

In alkanol R ¹⁶ is _{(C 1 -C 4) - -} 2- amino-alkyl, (C ₁ - ₄₎ - preferably represents hydrogen or alkoxy.

The T moiety in the 2-amino-phenol or formula (LII) is the same or different as the group containing halogen, alkyl (C ₁ -C ₄ ), O-alkyl (C ₁ -C ₄ ), NO ₂ or CF ₃ .

n means an integer of 1 to 4.

(b) Mixtures having five-membered rings containing sulfur and nitrogen atoms:

R ₁₆ in 2-mercapto-alkylamine has the meaning given above.

T and n in the 2-amino-thiophenol are as described above.

(C) Mixtures with five membered rings containing two nitrogen atoms:

For 1,2-diamino-alkanes

R ¹⁶ has the same meaning as described above,

R ¹⁶ is hydrogen, (C ₁ -C ₆ ) -alkyl, (C ₅ -C ₆ ) -cycloalkyl, optionally chlorine, (C ₁ -C ₄ ) -alkoxy, (C ₁ -C ₄ ) -alkyl or NO Benzyl or phenyl substituted with ₂ ;

In 1,2-phenylene-diamine, T and n have the meaning mentioned above.

(d) Mixtures having five-membered rings containing oxygen atoms and two nitrogen atoms are prepared from carboxylic acid hydrazides, carboxylic acid hydrazides, carboxylic acid esters or thiocarbamic acid esters or thiocarbamic acid S-esters. It is prepared as follows.

(e) Mixtures having 5-membered rings containing sulfur atoms and two nitrogen atoms are prepared from thiocarboxylic acid hydrazides, dithiocarbazine esters or thiosemicarbazides.

(f) A compound having a five-membered ring containing three nitrogen atoms is prepared from amidrazone, O-alkyl-semicarbazide, S-alkyl-thiosemicarbado, and aminoanidan.

(g) Compound (LX) is prepared from semicarbazide.

R ¹⁸ in the formulas (LVII), (LVIII), (LIX) and (LX) has the meanings given above.

R ¹⁹ is preferably hydrogen or alkyl (C ₁ -C ₁₂ ) optionally substituted with (C ₁ -C ₄ ) -alkoxy, phenoxy (optionally substituted with methyl or halogen), (C ₁ -C ₄ ) -alkyl-mercapto, mercapto-phenyl (optionally methyl, (C ₁ -C ₄₎ - or a halogen-substituted), or phenyl or naphthyl tarp (optionally methyl, (C ₁ -C ₄₎ - substituted with alkoxy or downward Gen Or cycloalkyl having 5 to 6 carbon atoms, optionally substituted with (C ₁ -C ₄ ) -alkyl:

Phenyl or naphthyl optionally substituted with hydrogen, (C ₁ -C ₄ ) -alkyl, CF ₃ , (C ₁ -C ₄ ) -alkoxy, (C ₁ -C ₄ ) alkylmercapto or NO ₂ ; 5- or 6-membered heterocyclic groups containing oxygen, sulfur and / or nitrogen as a hetero atom and which may contain fused or cyclic or additional heterocycles; Alkoxy having 1 to 12 carbon atoms; Optionally halogen, (C ₁ -C ₄ ) -alkyl, CF ₃ , (C ₁ -C ₄ ) -alkoxy, (C ₁ -C ₄ ) -alkylmercapto, (C ₁ -C ₄ ) -alkylsulfonyl, Phenyl substituted with NO ₂ or CN; Saturated or unsaturated alkyl mercapto containing 1 to 12 carbon atoms and optionally substituted with (C ₁ -C ₄ ) -alkoxy or phenyl (optionally substituted with chlorine, nitro, methyl or methoxy); Optionally (C ₁ -C ₁₂ ) -alkyl, (C ₅ -C ₆ ) -cycloalkyl, benzyl or phenyl (optionally halogen, C ₁ -C ₄ ) -alkyl, CF ₃ , NO ₂ , (C ₁ -C ₄ ) -Alkoxy or (substituted by (C ₁ -C ₄ ) -alkyl mercapto).

The reactions (a)-(g) are carried out by reacting compound (II) or (III) with at least equimolar amounts of supported reactants. Other substances may be added, for example the reactive component may be free of solvents or in organic solvents such as hydrocarbons (for example toluene or chlorobenzene), cyclic ethers (for example dioxane or tetrahydrofuran) or dimethyloxide. The reaction can be reacted with each other until the hydrogen chloride evaporation is completed.

These reactions are carried out at a temperature of 0 ° to 250 ° C, preferably 20 ° to 220 ° C.

However, if the reaction can be carried out by adding an acid binder, a double molar amount is used when compound (II) is used, and a triple molar amount is used when compound (III) is used. Suitable acid binders are: alkali metal oxides, hydroxides and carbonates and alkaline earth metal oxides, hydroxides and carbonates, as well as tertiary amines such as pyridine, triethylamine and N, N-diethylaniline and the like. The reaction temperature is -20 ° to + 120 ° C and 0 ° to 70 ° C is preferred.

However, 4,5-dichloro-imidazole substituted at the 2-position with a heterocyclic group is obtained by further reacting the second products of (II) and (III). For example, 2-thiazoro-4,5-dichloro-imidazole (LXI) is reacted by reacting 4,5-dichloro-imidazole-2-thiocarboxylic acid amide (XLIII) with a -halogeno-carbonyl compound. Make;

The process is the same as already described in the literature for other thiazole derivatives which react the reactants in water or in organic solvents such as hydrocarbons, alcohols, ethers, dimethylformamide, acetonitrile and the like, preferably in equimolar amounts. To promote the reaction, base metals such as alkali metal metal oxides, hydroxides and carbonates and alkaline earth metal oxides, hydrogen halides such as hydroxides and carbonates or tertiary amines such as triethylamine, N, N-dimethyl-aniline or pyridine Can be added. The reaction temperature is 0 ° to 150 ° C and 15 ° to 100 ° C is preferred.

In structural formula (LXI)

R ¹⁷ is hydrogen, alkyl (C ₁ -C ₁₂ ), cycloalkyl or aralkyl having a ring having 5 to 6 carbon atoms or optionally halogen, methyl, OH O-alkyl (C ₁ -C ₄ ), S-alkyl (C ₁ -C ₄ ) or NO ₂ represents an aryl substituted with an aryl moiety.

Both groups of R ¹⁷ may be bonded to each other to form a 5- or 6-membered carboxyl ring or a heterocycle.

The active compound according to the present invention has a broader herbicidal action and is superior to the benzimidazole-2-carboxylic acid derivative. The active compound is effective in both pre-germination and post-germination treatment. If this active compound is used as a total herbicide, post-germination use is preferred, whereas if these compounds are used to selectively control weeds, it is preferable to use it as a germination pretreatment. The amount of active compound used varies over a wide range. This inherently depends on the desired effect. Generally, 0.1 to 25 kg / mm 3 and 0.25 to 10 kg / mm 3 are preferred.

The compounds are suitable for controlling weeds in cereals, cotton and corn and as selective herbicides. It can also be used as a total herbicide when used in large quantities. The use to selectively control weeds and as a total herbicide depends largely on the dosage.

The active compounds according to the invention affect plant growth and can therefore be used as deciduous, desiccant, broadleaf plants, herbicides, germination inhibitors and in particular herbicides. In a broad sense weeds are all plants that grow in areas where they are not needed. The use of the compounds according to the invention when used as total herbicides or as selective herbicides depends.

The active compound according to the present invention can be used, for example with respect to the following plants.

Mustard (Sniapis), Rapidi, Galiun, Stellaria, Medriearia, Anthemis, Glinsoga, Chinopodium, Nettle, Urica, Senceio, Chinenopodium, Pursula (Portulaca), Xanthium, Plum (Lonvolvalus), Morning Glory (Ipomoea), Polygonum, Sesbonia, Ambrosia, Sirbro Cirsium, Cardaus, Bonchus, Solanum, Rorippa, Rotala, Lindernia, Lamium, Purslane Dipotent plants such as Veronica, Viola, Galeopsis, Popaver, and Centaurea;

Gossypium, Glycine, Beet, Carrot (Daucus), Bean (Phaseouls), Pea (Pisum), Potato (Soℓanum), Linum, Ipomoea, Vicia ), Dicotyledonous plants such as Tobacco (NIcotiana), Tomato (Lycopersicon), Parachute (Arachis), Cabbage (Brassica), Lactuca, Cucumis, and Cuburbita; Echinochloa, Setaria, Panicum, Digitavia, Phoeum, Poa, Fostuca, Eleasine, Brachiaria, Lolium, Bromus, Oat, Avena, Cyperas, Sorghum, Agroyron, Cynodon, Stiletto Monocharia, Fimbristylis, Sagittaria, Elecocharis, Scirpus, Puspalum, Ischaemum, Sphenoclea Monocotyledonous weeds such as Dicreloetenium, Whitefish (Aggrostis), Alopecu-rus, and Apera;

Rice (Oryzae), Corn (Zea), Wheat (Triticum), Barley (Hordeum), Oats (Avena), Rye (Secale), Sugar Cane (Sorghum), Millet (Panicum), Beet (Saccharum), Pineapple (Ananas) ), Monocotyledonous plants such as asparagus and onion (Allium).

However, the use of the active compounds according to the present invention can be used in other ways as usual in other plants as long as they are not limited to these plants or the indicated plants.

Depending on the concentration, the compound can be used, for example, for controlling weeds such as industrial land and railroads, and roads and forests. Similarly, the compounds can be used to control weeds in perennial plantations such as plantings, arboretums, orchards, vineyards, citrus plantations, chestnut plantations, banana plantations, coffee plantations, black tea plantations, rubber plantations, oil palm plantations, and hop plantations. It is used to selectively control weeds of annual crops.

The active compounds according to the invention can be mixed with the active compounds with other herbicidal action in preparations to achieve a wide range of actions depending on the intended use. In particular the active compounds described below and other representative active compound groups are suitable for mixing.

2,3,6-trichloro benzoic acid and salts thereof,

2,3,5,6, -tetrachloro benzoic acid and salts thereof,

3-nitro-2,5-dichloro benzoic acid and salts thereof,

3-amino2,5-dichloro benzoic acid and salts thereof,

2-methoxy-3,6-dichlorobenzophosphoric acid and salts thereof,

2-methoxy3,5,6-dichlorobenzophosphoric acid and salts thereof,

2,6-dichloro-thiobenzamide,

2,6-dichlorobenzonitrile,

2,4-dichloro phenoxyacetic acid and salts and esters thereof,

2,4,5-trichloro phenoxy acetic acid and salts and esters thereof,

2-methyl-4-chlorophenoxy acetic acid and salts and esters thereof,

2 (2,4-dichlorophenoxy) -propionic acid, 2- (2-methyl-4-chloro phenoxy-propionic acid and 2- (2,4,5-trichloro phenoxy) -propionic acid and salts thereof and Esters, 4- (2,4-dichloro phenoxy) -butyric acid and salts and esters thereof, 4- (2-methyl-4-chloro phenoxy) -butyric acid and salts and esters thereof, 2,3,6- Trichloro phenyl acetic acid and its salts and 4-amino-3,5,6-trichloro picolinic acid.

Trichloro acetic acid and salts thereof 2,2-dichloro-propionic acid and salts thereof, 2-chloro-N, N-diallylacetic acid amidedinitro cresol and dinitro-butylphenol and salts thereof

3-phenyl-1,1-dimethyl urea, 3- (4'-chlorophenyl) -1,1-dimeltyl-urea, 3- (3 ', 4'-dichlorophenyl) -1,1-dimethyl-urea , 3- (3 ′, 4′-dichlorophenyl) -1,1-urea, 3- (3 ′, 4′-dichloro phenyl) -1,1,3trimethyl-urea, 3- (4′-chlorophenyl -1-methoxy-methyl-urea,

3- (3′-trifluoro methyl-phenyl) -1,1-dimethyl-urea,

3- (3 ′, 4′-trifluoro methyl-phenyl) -1-methoxy-1-methyl urea,

(3- (4′-bromophenyl) -1-methoxy-1-methyl-urea, 3- (3 ′, 4′-dichlorophenyl) -3-methoxy-dimethyl-urea, 3- (4 ′ -Glo-phenoxyphenyl) 1,1-dimethyl urea, N-cycloolyl-N, N-dimethyl-urea 3 () benzthiazol-2-yl) -1,3-dimethyl urea, 3- (3 -Chloro-4-methylphenyl) -1,1-dimethylurea.

N, N-di- (n-propyl) -Sn-propyl-thiocarbamic acid ester, N-ethyl-N- (n-butyl) -Sn-propyl-thio carbamic acid ester, N, N-di- ( n-propyl) -S-ethyl-thiocarbamic acid ester, N-phenyl-O-isopropyl-carbamic acid ester, N- (m-chlorophenyl) -O-isopropyl-carbamic acid ester, N- (3 ' , 4'-dichlorophenyl) -O-methyl-carbamic acid ester, N- (m-chlorophenyl) -O- (4-chloro-butyn-2-yl) -carbamic acid ester, N- (3'-methylphenyl ) -O- (3-methoxy-carbonylaminophenyl) -carbamic acid ester and N, N-diisopropyl-thiocarbamic acid 2,3,3-trichloroalkyl ester

3-cyclohexyl-5,6-trimethylene-uracil, 5-bromo-3-secondary-butyl-6-methyl-uracil, 3,6-dioxo-1,2,3,6-tetrahydropyri Chopped, 4-amino-5-chloro-1-6-pyrizone. 2-Chloro-4-ethylamino-6-isopropylamino-S-triazine, 2-chloro 4,6-bis- (methoxypropylamino) -S-triazine, 2-methoxy-4,6- Bis- (isopropylamino) -S-triazine, 2-diethyl amino-4-isopropyl-acetamido-6-methoxy-S-triazine, 2-isopropylamino-4-methoxy-propyl Amino-6-methylthio-S-triazine, 2-methylthio-4,6-bis- (isopropylamino) -S-triazine, 2-chloro-4,6-bis- (ethylamino) -S -Triazine, 2-methyllio-4,6-bis- (ethylamino) -S-triazine-2-methoxy-4-ethylamino-6-isopropylamino-S-triazine, 2-methylthio 4-ethylamino-6-isopropylamino-S-triazine, 2-methoxy-4,6-bis- (ethylamino) -S-triazine and 2-chloro-4,6-bis- (iso Propylamino) -S-triazine.

N, N-diethyl-2,4-dinitro-6-trifluoromethyl-1,3-phenylene-diamine, N, N-di-n-propyl-2, 6-dinitro-4-tri Fluoromethyl-aniline, 4'-nitro-2,4-dichloro-diphenyl ester, 3,4-dichlorophenyl-propion amide and 2 ', 6'-diethyl-N- (methoxymethyl) -2- Chloroacetanilide,

The compounds according to the invention exhibit potent bactericidal and bactericidal effects. These compounds do not damage crops at the concentrations necessary to control fungal bacteria. For this reason, it is suitable for use as a plant protection agent for controlling fungi and bacteria. Among fungicides, fungicides control Plasnoclio phoromycetes, Oomycetes, Hytridiomycetes, Zygomycetes, Ascomycetes, Basidio-mycetes, and Deuteromycetes. Used to.

Other active compounds of the present invention have a wide range of action and can be used for seed transmission pathogens as well as fungi that infect plants in the ground or plants in the soil.

The active compounds according to the invention are particularly useful in the case of Pyocera leucotricha of apples, as well as Pyocera leucotricha of apples, and of rice, in the case of rice, as well as rust and co-rust of cereals caused by Puccinia species. Pyricularia oryzae and Pellicularia sasskii have a high effect against fungal pathogens. With respect to above-ground plants, the compounds are effective against Botrytis species, Srptoria species, Helminthosphorium species and Sercospora species.

The active compounds according to the present invention are seedling diseases, rhizome disease, and species of Fusarium, Rhizoctonia species, Verticillium eggs against plant pathogens attached to seeds or caused by soil. It is particularly effective against phytopathogenic fungi that cause seed quality, such as Verticillum alboatrum and Ppialophora cinerescens.

The active compounds according to the present invention are resistant to plants on farmland necessary to control fungal and bacterial pathogens.

The active compounds are useful for controlling cropland and forest lands and marine animal sea breezes, especially insects or arachnids and nematodes. These compounds are effective against sensitive and resistant species or for all species or growth stages.

The above pests are as follows.

Isopoda River, for example Oniscus asellus, Armadillium-ium rulhare, Porcellio scaber, Diplooda river, For example, Braniulus gutlulatus, Chilopoda rivers, for example Geophilus carpop-hagus and Scufigera species, Symphla ) Rivers, for example Scutigerella immaculata; Thysanura, for example Lepisma saccharina, Collembola, for example Onychiurus armatus, Orthoptera includes, for example, the wingwheel (Blattagermanica), the acheta americana, the Leucophaue maderae, the wheel (Blattella grermanica), and the Acheta domesticus. , Glylotalpa SPP, Locusta Migratoria migrat orides, Melanopus differentiali, and Schistocerca gregaria, Dermaptera, for example Porpicula auricularia; Isoptera includes, for example, Reticulitermes SPP .; Anoplura, for example Phylloxera vastatrix Pemphogus spp., Pedicurus humanus corporis, Haematopinus spp. .), And Cinognathus spp., Mallophaga, for example Tricodectes spp., And Damalinea spp .; For Thysanoptera, for example Hercinoth femorarilips and Thrips tabaci felling, for example, Eurygaster SPP. Dysdercus intermedius, Piesma quadrata, Cimex lectularius, Rhodnius prolixus and Triatoma spp .; Homoptera includes, for example, Aleurides brassicae, Bemisia tabaci, Triareurodes vaporariorum, and Aphids gossyppi. ), Brevcoryne brassicae, Cryptomyzus ribis, Doralis fabae, Dolris pomi, Eriosoma lanigerum, Peach powder aphid Hyalopteros arundinis, Black aphid subspecies (Myzus SPP.), Porodon dendrobium (Phoroden), Rhopalosiphum, Empoascax spp., Lecanium corni Cyszethiao Sassetia oleae, Laodelphax striatellus, Nilapparvata lugens, Aonidiella aurantii, Aspidoptera, Powdered pod beetle subspecies (Pseudococcus SPP.) And Fusilla subspecies (Psylla SPP.); Lepidoptera includes, for example, Peptinophora gossypiella, Bupalus piniarius, Cheima tobia brumatu, Licholcollis blancardella. , Apple moth (Hyponomeuta padella), Chinese cabbage moth (Plutella maculipennis), tent moth (Malacisima neustria), patterned white moth (Euproctis chysorrhoea), Lmanantria spp. ), Phyllocnistis citrella, Agrotis SPP., Moth (Euxoa SPP.), Fetia SPP., Earias insulana, Heliotis subspecies SPP.), Laphygma exigua, Mamestra brassicae, Panolis flammea, Prodenia litura, Spodoptera SPP. , T Tricholisiani, Carpocapsa pomonella, Pieris SPP. Chilo SPP. Pyraustra nubilalis Ephestia knhniella ), Galleria mellinella, Cacocia poana, Cadua reticulana, Choristoneura fumiferana, Clysia ambiguella, Ho Mona magnanima: (Homona magnanima), and Tortrix virdana;

Coleoptera includes, for example, Anobium punctatum, Rhizopertha dominica, Bruchidius obtectus, Acanthos Celides of Techtis, etc. Hilotrupes bajulus, Agelasticaalni, Leptinotaesa decemlineata, Phaedon cochleariae, Diabrotica SPP. ), Psylliodes Chrysocephala, Epilakna Varivestis, Atomaria SPP., Oryzaephilus surinamensis, Antonomis subspecies Sitophilus SPP., Otiorrhynochus sulcatus, Cosmopolites sordidus, Cerrorhynchus assi milis, Htpera positica, Permestes subspecies (Permestes SPP.), Trigoderma subspecies (Trogoderma spp.), Anthrenus subspecies (Athgenus spp.), Atenagen subspecies (Attagenus spp. Lyctus SPP., Megegethes aebeus, Ptnus SPP., Niptus hololeucus, Gibbium pyslloides, Tribolium, Tenebrio molitor, Agriotes SPP., Conoderus SPP., Melontaron melononta, Ampilonolsti Amphimallon sostitalis, and Costelytra zealandica ,; Hymenptera includes, for example, Diprion subspecies (Diprion SPP.), Hoplocampa subspecies, Lasius SPP., Monomorium pharaonis, and Vespa subspecies. .);

Dipteria, for example Aedes subspecies (Aedes SPP.), Anopheles subspecies (Anopheles SPP.), Curex subspecies (Culex SPP.), Drosophila melanogaster, Housefly subspecies (Musca SPP. ), Baby Flies subspecies (Fannia SPP.), Califora erythrocephola, Lucilia SPP., Chrysomyia spp., Cuterebra spp., Gastrophijus spp., Hypopobosca spp., Stomoxya spp., Destrus spp., Hypoderma spp., Taba Tabanus SPP., Tannia SPP., Vibol hortulanus, Oscinella frit, Porbia spp., Pegomia hisosiami (Peogomyia hyoscyami), Ceratitis capitata, Dacus oleae, and Tipra Tipula paludosa; Siphonaptera includes, for example, Xenopsylla cheopis, and Ceratophyllus SPP .; Arachnida includes, for example, Sxorina, and Latrodetus macrans; Acarina, for example, Acarus Siro, Argas SPP., Ornithodoros SPP., Dermanyssus gallinae, Erio Eriophyes ribis, Phyllocoptruta oleivora, Buphillus spp., Rhipicephalus spp., Amblyomma spp., Hyaloma Hyalomma SPP., Ixodes SPP., Psoropts SPP., Choriopte SPP., Saroptes SPP., Tarsonnemus subspecies ( Tarsonenus SPP.), Breyobia praetiosa, Panonychous SPP. And Tetranycus SPP., And plant parasitic nematodes are Prattylenchus SPP., Radophorus Radopholussimlis, Stem nematode (Ditylenchus sipsaci), and nematode nematode (Tylench) ulus semi-penetrans, Hetero-dera SPP, Black Nematode (Meloidogyne SPP.), Chrysanthemum Leaf Nematode (Aphlenchoides SPP.), Longidorus SPP., Xiphonema SPP. .), And Teicochodorus SPP.

Synthetic compounds according to the present invention can be converted into conventional formulations such as solutions, emulsions, suspensions, powders, pasta preparations and granules. These preparations can be made by known methods of mixing the active compound with an extender, i.e., a weight or carrier or optional, of liquid or solid or liquefied gaseous with a deactivating agent, i.

When water is used as the weighting agent, for example, an organic solvent can be used as a cosolvent.

Liquid diluents or carriers include aromatic hydrocarbons such as xylene, toluene, benzene or alkyl naphthalene, chlorinated aromatic or aliphatic hydrocarbons such as chlorobenzene, chloroethylene or methylene chloride, aliphatic hydrocarbons such as cyclohexane or paraffin, eg inorganic O-ring fractions. Alcohols such as glycols, butanes, as well as esters and ethers thereof, ketones such as acetone, methyl ethyl ketone, methyl isoburyl ketone or cyclohexane, or water such as dimethylformamide, dimethylsulfoxide or acetonitrile Preference is given to using strong polar solvents.

An extender or carrier of a liquefied gaseous means an aerosol spray such as a liquid that is a gaseous at normal temperature and pressure, for example a halogenated hydrocarbon, such as furion.

Solid weights or carriers include ground natural minerals such as kaolin, clay, talc, choke, quartz, attapulkit, montmorillonite, or diatomaceous earth or ground synthetic synthetic minerals such as highly dispersed silicic acid, alumina or silicate Preference is given to using.

Preferred examples of emulsifiers and foaming agents are polyoxyethylene-fatty acid esters such as alkylarylpoly glycol esters, alkylsulfonates and arylsulfonates, as well as nonionic and anionic emulsifiers such as albumin hydrolysis products, and the like. Sulfite waste liquor and methylcellulose.

The active compounds according to the invention can be prepared by mixing with other active compounds such as fungicides, insecticides and acaricides.

The formulations generally contain from 0.1 to 95% by weight of the active compound and preferably from 0.5 to 90 percent. The active compounds can be used in the form of preparations in commercially useful forms or in useful forms prepared from these preparations. The amount of active compound used in commercially useful formulations varies. The concentration of the active compound is generally preferably 0.0000001 to 100%. The active compound is appropriately formulated and used by conventional methods.

In particular, when used as a foliar fungicide, the concentration of the active compound varies in a wide range. These are generally 0.1 to 0.00001 weight percent (%), with 0.05 to 0.00001% being preferred.

In the case of treatment with seeds, the active compound is generally used in an amount of 0.001 to 50 g, preferably 0.01 to 10 g per kg of seed.

In soil treatment, the amount of active compound is used in the range of 1 to 1,000 g, preferably 10 to 200 g, per cubic meter of soil.

When used against pests that damage health and pests, chemical compounds have a turbid residual effect on wood or clay and have a high stability for alkalinizing lime substrates.

A nematode, a shellfish killing agent, a bactericidal or herbicidal composition according to the present invention may be prepared by mixing the active ingredient compound of the present invention with a solid or liquefied gaseous weight or carrier, or including a surfactant, or a liquid weight or Mix with the carrier.

The present invention is also characterized in that it is used in the form of a mixture of the present invention itself or a mixture of the active ingredient with a weight agent and a carrier on the host of beetle, nematode, fungus or weeds. Or weed control method.

The present invention also protects crops by using the compounds of the present invention alone or in the form of compositions mixed with a weight or carrier before and / or during the growth of the crop. It will be appreciated by the present invention conventional methods of enhancing crop yields.

The insecticidal, acaricide, bactericidal and herbicidal action of the compounds according to the invention can be explained by the following biological test examples, and the active compounds according to the invention have each been identified as various corresponding preparation examples.

Known comparative compounds are represented by the following letters.

Example A

Post-germination treatment test

Solvent: 5 parts by weight of acetone

Emulsifiers: To prepare a suitable formulation of 1 part by weight of an alkylaryl polyglycol ether active compound, 1 part by weight of the active compound is mixed with this amount of solvent, the amount of emulsifier is added and the concentrate is diluted with water to the desired concentration.

Test plants 5 to 15 cm in height are sprayed into the preparation of the active compound by application of the amount of the active compound per unit area indicated in the table and thinly. The concentration of the sparse liquid is selected so that the amount of the active compound specified in the table can be used 2,000 liters of water per hectare.

Crop damage after 3 weeks is expressed as percent damage compared to untreated control plants.

0% = no damage (such as untreated control plants)

100% = damages all.

Active compounds, dosages and results are shown in the following table.

TABLE A

Example B

Pre-germination Treatment Test

Solvent: 5 parts by weight of acetone

Emulsifier: To prepare 1 part by weight of an alkyl aryl polyglycol ether active compound into a suitable formulation, 1 part by weight of the active compound is mixed with this amount of solvent and the amount of emulsifier is added to dilute this concentrate with water to the desired concentration.

Seeds of the test plants are sown in soil and sprayed with the preparation of the active compound 24 hours later.

It is convenient to keep a certain amount of water per unit area.

The concentration of the active compound in the formulation is irrelevant only to determine the amount of active compound used per unit area.

After 3 weeks, the percent damage is determined by comparing the degree of damage of the plant to the untreated control.

0% = no damage (such as untreated control plants)

100% = damages all.

Active compounds, dosages and results are shown in the following table.

TABLE B

Example C

Paper liquor treatment test / grain rust / protection

(Foliar damage bacteria)

To prepare a suitable formulation of the active compound, 0.25 parts by weight of 25 parts by weight of dimethylformamide and 0.06 parts by weight of emulsifier W are added and 975 parts by weight of water are added. Dilute the concentrate with water to the desired concentration of the spray.

To test for protective action, the wheat crop, an adiabatic strain of the Michigan amber strain, is inoculated with a suspension of Puccinia vecondita uredospoa suspended in 0.1% liquid agar. After drying the spore suspension, the prepared active compound is left in the greenhouse for 24 hours at 20 ° C. and 100% relative humidity for spraying and incubating until the drop drops.

After 10 days of breeding at 20 ° C. and 80-90% air humidity, the rust lesions on crops are evaluated. Leaf infection was evaluated by dividing by 1 to 9 indices. 1 indicates a 100% effect, 3 indicates a very high effect, 5 indicates a moderate effect 9 has no effect.

The active compounds, the concentrations of the active compounds in the spray solution and the degree of infection can be seen in the table below.

Example D

Mycelial growth test

Nutritional medium used: 20 parts by weight of agar-agar

200 parts by weight of potato juice

5 parts by weight of malt

15 parts by weight of dextrose

5 parts by weight of peptone

2 parts by weight of NA ₂ HPO ₄

0.3 parts by weight of CA (NO ₃ ) ₂

Solvent Mixing Ratio of Nutritional Medium: 2 parts by weight of solvent mixture

100 parts of Baby Nutrition Medium

Composition of the solvent mixture: 0.19 parts by weight of DMF or acetone

0.01 part by weight of emulsifier (alkyl, polyglycol ether)

1.80 parts by weight of water

The amount of active compound needed to bring the concentration of the desired active compound in the nutrient medium is mixed with the mixture in this amount of solvent.

The concentrate is thoroughly mixed with the liquid nutrient medium (cooled at 42 ° C.) and poured into a petri dish 9 cm in diameter. Fix the control preparation without addition of the formulation.

When cooling and solidifying the nutrient medium, the plates are inoculated with the species described in the table and incubated at 21 ° C. It is evaluated after 4 to 10 days depending on the growth rate. In the evaluation, the radial growth of mycelium on the treated nutrient medium is compared with the growth on the control nutrient medium.

The fungus used the following values to assess growth.

1 = no growth of bacteria

3 = very strong growth inhibition

5 = moderate growth inhibition

7 = Slightly inhibited growth

9 = growth equal to no treatment control

Active compounds, active compound concentrations and results are shown in the following table.

TABLE D

Example E

Phaedan Larva Test

Solvent: 3 parts by weight of dimethylformamide

Emulsifier: 1 part by weight of alkylaryl polychol ether

To prepare a suitable formulation of the active compound, 1 part by weight of the active compound is mixed with the above amount of solvent containing the above amount of emulsifier and the concentrate is diluted with water to the desired concentration.

Cabbage leaves (Brassica Oleracea) are moistened with a preparation of the active compound and then infected with reporter aphid larvae (Phaedon cochleariae).

After incubation for a period of time, the extent of infection is determined in percent.

100% means that all grass larvae have been killed, and 0% means that aphid larvae are not killed.

The active compounds, their concentrations, the timing of evaluation and the results are shown in the following table.

TABLE E

Example F

Plutella Test

Solvent: 3 parts by weight of dimethylformamide

Emulsifier: parts by weight of alkyl aryl polyglycol ether

To make a suitable formulation of the active compound, 1 part by weight of the active compound is mixed with the above amount of solvent containing this amount of emulsifier and the concentrate is diluted with water to the desired concentration.

Cabbage leaves (Brassica oleracea) are sprayed with a preparation of the active compound until they are moistened, and then infected with a caterpillar (plitella maeclipennis) with a lozenge-patterned back.

The degree of death was expressed as a percentage after incubation for a period of time: 100% means that all caterpillars were killed and 0% means that the caterpillars were not killed.

The active compounds, their concentrations, the timing of evaluation and the results are shown in the following table.

TABLE F

Example G

Tetranychus test (resistance)

Solvent: 3 parts by weight of dimethylformamide

Emulsifier: 1 part by weight of alkylaryl polyglycol ether

To make a suitable formulation of the active compound, 1 part by weight of the active compound is mixed with this amount of solvent and the amount of emulsifier and the concentrate is diluted with water to the desired concentration.

The two-point arachnid mite mucosa is sprayed with a preparation of the active compound until it is moistened on the soybean crop (Phaseolus vulgaeis) infected with mite (Tetranychus urticae).

After a period of time, the degree of death was expressed as a percentage. 100% means that all of the solvent of the arachnid is killed and 0% means that the mite of the arachnid is not killed.

The active compounds, their concentrations, the timing of evaluation and the results can be found in the following table.

TABLE G

Example H

Phytophthora test (tomato) / protection

Solvent: 4.7 wt% acetone

Emulsifier: 0.3 parts by weight of alkylaryl polyglycol ether

Water: 95 parts by weight

The amount of active compound necessary to bring the desired concentration in the spray liquid is mixed with this amount of solvent and the concentrate is diluted with this amount of water containing the additive. Spray young tomato crops 2-4 rows with spray until wet. This crop is left in the greenhouse for 24 hours at 20 ° C. and 70% relative atmospheric humidity.

The tomato crops are then inoculated with a liquid spore suspension of Phytoghthora infestans.

The crops are left in a wet room at 100% atmospheric humidity and 18-20 ° C. After 5 days the infection of the tomato crop is determined. Evaluation data are expressed as percent infection. 0% means no infection and 100% means that the crop is fully infected.

The active compounds, their concentrations and the results can be found in the following table.

TABLE H

Example I

Lean Treatment Test / Grain Rust / Protection (Side Damage)

To prepare the active compound in small amounts, 0.25 part by weight of the active compound is dissolved in 25 parts by weight of dimethylformamide and 0.66 parts by weight of an alkylaryl polyglycol ether emulsifier and 975 parts by weight of water is added. The concentrate is diluted with water to a sparging solution of the desired final concentration.

To test for control, young wheat, a Michigan amber variety, is inoculated with a solution of quniccia recondita uredo spoa suspended in 0.1% strength agar. After drying the spore suspension, the prepared active compound is left in the greenhouse for 24 hours at 20 ° C. and 100% relative humidity to spray and incubate until dew drops are produced.

The crops are incubated at 20 ° C. and 20-90% atmospheric humidity for 10 days to assess the rust symptoms present in the crops. The extent of infection is expressed as percent infection relative to untreated control plants. 0% indicates no infection and 100% indicates infection to the same extent as untreated controls. The more effective the active compound, the lower the degree of rust infection.

The active compounds, the concentrations of the active compounds in the spray solution and the degree of infection are shown in the following table.

The process according to the invention is illustrated by the following preparation examples.

Example 1

Anhydrous hydrogen chloride is passed through a solution in which 218 g (0.1 mol) of 4,5-dichloro-2-tachloro-methylene-imidazole is dissolved in about 2 liters of anhydrous toluene until precipitation (at least 1 mol) formation is complete. After cooling (addition reaction with hydrogen chloride is exothermic), it is filtered and dried to yield 235 g (89% of theory) of 4,5-dichloro-2-trichloromethyl-imidazole having a melting point of 201 ° C. (decomposition). .

Example 2

25 g of 4,5-2-dichloromethylene-imidazole was dissolved in 100 ml HF, and maintained at 100 ° C. in an autoclave and stirred for 4 hours. After cooling and depressurizing, the excess HF is distilled off. The residue is taken up in ether and washed briefly with cold water twice, then dehydrated with sodium sulfate and the solvent is removed.

Recrystallization once with toluene / washing benzine yields 4,5-dichloro-2-dichloro-fluoromethyl idamidazole. Melting Point: 172 ° C (Decomposition)

Example 3

380 g of 4,5-dichloro-2-trichloromethyl-imidazole are first placed in a fluorinated autocrabo and then 400 ml of HF is injected at 0 ° C. Seal the autoclave and inject Cl ₂ as a fill gas under a pressure of about 2 atmospheres.

The mixture is heated to 100 ° C. over 1 hour and raised to 140 ° C. over 2 hours. This temperature is maintained for 3½ hours.

As HCℓ is produced, the pressure drops and the pressure drops to 20 bar through the condenser using a calibration valve. After cooling and depressurization, the remaining HF is distilled off and the residue is dissolved in tetrahydrofuran and the solution is mixed with NaF and shaken. Filtration and distillation of the solvent gave 4,5-dichloro-2-trifluoromethyl-imidazole having a melting point of 186 to 188 ° C.

Example 4

25.5 g (0.075 mol) of 4,5-dichloro-2-trichloromethyl-imidazole at 10 to 15 ° C with vigorous stirring, 28.2 g (3 mol) of phenol, 27.3 g (0.3 mol) of concentrated sodium hydroxide solution and dioxane In small amounts to 200 ml of the mixture. The reaction mixture was further stirred at room temperature for 2 more acids, and then 1 liter of water was added thereto. The separated crystals are filtered off and dried. Yield: 25 g (78% of theory) | 4,5-Dichloro-2-tris- (4-dichlorophenoxy) -methyl-imidazole is obtained. Melting Point: 192-194 ° C. (Ethyl Acetate)

Example 5

4-chlorobenzene was used instead of phenol to convert 4,5-dichloro-2-tris- (4-dichlorophenoxy) -methyl-imidazole of the structural formula.

Obtained in the same manner. Melting Point: 220-222 ° C (butanol)

Example 6

Pass 9.2 g (0.4 mol) of sodium in 300 ml of ethanol until the methyl mercaptan solution is saturated. 25.4 g (0.1 mol) of 4,5-dichloro-2-triro-methyl-imidazole are added to this solution in small portions at 0-5 ° C. When the mixture is stirred at room temperature for 2 hours or more, sodium chloride is separated and the filtrate is evaporated in vacuo. The residue is dissolved in 300 ml of water and the mixture is acidified with hydrochloric acid. The separated crystals are filtered off, washed with water and dried. 4,5-Dichloro-2-tris (methyl-merto) -methyl-imidazole having a melting point of 175 to 177 ° C. (toluene) is obtained.

Example 7

50 g (0.23 mol) of 4,5-dichloro-2-dichloromethylene-imidazole is boiled with 250 ml of water for 5-10 minutes to tongue the colorless solution. After cooling, the colorless crystals of 4,5-dichloro-imidazole-3-carboxylic acid monohydrate were separated. It dissolves at 180 ° C. (decomposes by decarbonate to form the known 4,5-dichloro-imidazole. Yield: 35 g (80% of theory). 4,5-dichloro-2-methyl-imidazole Compound is obtained.

Example 8

40 g (0.44 mole) of 50% strength hydrochloric acid in concentrated hydrochloric acid was added until the acid reaction was completed, and then the mixture was obtained with 21.8 g (0.1 mole) of 4,5-dichloro-2-dichloro-methylene-imidazole. Boil briefly until lost. After cooling the solution is weakly alkaline with sodium bicarbonate. The precipitate formed is filtered off, washed with water and dried. In this manner, 14 g of ethyl amine salt (62% of theory) of 4,5-dichloro-imidazole-2-carboxylic acid having a melting point of 290 ° C is obtained. The product can be recrystallized from water as long needles.

Example 9

The isopropyl amine salt of 4,5-dichloro-imidazole-2-carboxylic acid having a melting point of> 290 ° C is obtained by the same method as in Example 8.

Example 10

560 g (2.56 mole) of 4,5 dichloro-2-dichloromethylene-imidazole was slowly added to 1 kg (13.2 mole) of glycol monomethyl ether while stirring while cooling slightly to maintain the temperature of the exothermic reaction at 80 to 100 ° C. The compound is then evaporated and dried in vacuo. In this way 4,5-dichloro-imidazole-2-carboxylic acid methoxyethyl ester is obtained in good yield. Melting point 130 ℃

4,5-dichloro-2-trichloromethyl-imidazole is used instead of 4,5-dichloro-2-dichloromethyl-imidazole to obtain the same compound, in which case the reaction mixture is continuously Heat to 90-100 ° C.

The 4,5-dichloro-imidazole-2-carboxylic acid ester of the following structural formula is obtained in the same manner.

TABLE 1

Example 41

Stirring and about 10 to 65 ml of a cyclohexane sulfuric acid in a mixture of 130 g (0.65 ml) of 4,5-dichloro-imidazole-2-carboxylic acid monohydrate (see Example No. 7 for the preparation thereof) and 1.3 L of dioxane Droplets were added dropwise while cooling to 20 ° C. The isobutylene gas is then passed through the reaction mixture at room temperature for about 12 hours. After being left overnight, excess dissolved isobutylene and dioxane are removed in vacuo at room temperature and the residue is placed in about 5 l of ice water. The precipitate formed is filtered and sebenha then dried with water to give 43 g (28% of theory) of 4,5-dichloro-imidazole-2-carboxylic acid tert-butylester.

The melting point is 180 deg.

Example 42

9.4 g (0.1 mol) of phenol and 25.4 g (0.1 mol) of 4,5-dichloro-2-trichlormethyl-imidazole are dissolved in 150 ml of tetrahydrofuran. 27 g (about 0.3 mol) of concentrated sodium hydroxide solution are inexpensive to the solution at 0 to 5 ° C with vigorous stirring. The mixture is stirred for 1 hour while cooling, and then further stirred at room temperature for 1 hour. Then 1 liter of water is added and the mixture is acidified with hydrochloric acid, and the separated crystals are filtered. Washing with water and drying gave 11.2 g (43.5% of theory) of 4,5-dichloro-imidazole-2-carboxylic acid phenylhydro. Melting point 102 to 103 ° C (in toluene)

Example 43

Using 4-nitro-phenol instead of phenyl to obtain 4,5-dichloro-imidazole-2-carboxylic acid 4-nitrophenyl ester of the following structural formula having a melting point of 216 to 218 ° (in ethanol) in the same manner as above. do.

Example 44

19.6 g (0.1 mol 0) of methyl 4,5-dichloro-imidazole-2-thiocarboxylic acid amide and 17 g (0.12 mol 0) of methyl iodide are dissolved in 150 ml of dioxane and boiled under reflux for 3 hours. The filtrate was filtered off and the solution was evaporated in air, the residue was stirred with a solution of approximately 50% strength hydrochloric acid, the product was filtered off, washed with water and dried to form 4,5- at a melting point of 162 to 164 ° C. 63% of 13.5 g 9 theory of dichloro-imidazole-2-thiocarboxylic acid S-methylhydro) are obtained.

Example 45

24 g (0.2 mol) of 3-methylaminopropionitrile hydrochloride was added to a solution of 21.8 g (0.1 mol) of 4,5-dichlor-2-dichloromethylene-imidazole in 100 ml of dioxane, followed by stirring the mixture. Heat to reflux for 2 hours. After cooling, the product was precipitated with water, filtered, washed with water and dried to give 16.5 g of 4,5-dichloro-imidazole-2-carboxylic acid N- (2-cyanoethyl) -N-methylamide (Theoretical 67 %) Is obtained. Melting point 184 ° C. (in acetonitrile) The 4,5-dichloro-imidazole-2-carboxamide of the following structure can be obtained in a similar manner.

TABLE 2

Example 50

25.4 g (0.1 mol) of 4,5-dichlor-2-trichloromethyl-idamidazole are added to a mixture of 30.3 g (0.3 mol) of diisopropylamine and 150 ml of methanol in small portions at 0? 5 占 폚. The mixture is stirred at room temperature for at least 1 hour, then 150 ml of water is added and the mixture is stirred at room temperature for 1 hour. The mixture is acidified with hydrochloric acid and then cooled with ice. The separated crystals were filtered, washed with water and dried to give 16.5 g (62.5% of theory) of 4,5-dichloro-imidazole-2-carboxylic acid diisopropiamide. Melting point 133 to 135 ° C (cleaning benzine)

Example 51

(a) 654 g (3 mol) of fine powdered 4,5-dichloro-2-dichloromethylene-imidazole was first added to a mixture of 783 g (9 mol) of isopropylformamide, 162 g (9 mol) of water and 3 liters of acetonitrile. A small amount is added over 1 hour with stirring and cooling to 0 ° C.

The clear solution is then poured into about 15 kg ice water. The resulting white precipitate was filtered, washed with water and dried to give 630 g (84% of theory) of 4,5-dichlor-imidazole-2-carboxylic acid-N-formyl-isopropylamide having a melting point of 142 ° C. To obtain. The same result can be obtained without adding water.

(b) 21.8 g (0.1 mol) of fine powdered 4,5-dichloro-2-dichloro-methylene-imidazole was partially added to 87 g (1 mol) of isopropyl-formamide while stirring to bring the reaction mixture to about 40-50. Warmed to ° C. After the exothermic reaction is complete, the reaction mixture is placed in excess ice water. A viscous precipitate is formed first, which is left for 1 hour and then solidified. After filtration, washing with water and drying yields 23 g of material, which is generally the same as the product of (a). Melting Point Approximately 132-137 DEG C. The poorly soluble second component can be separated and fractionated crystallized in acetonitrile to separate the product of (a) having a melting point of 142 DEG C in pure form.

(c) When the process of (b) was carried out at a reaction temperature of about 100 ° C., it was observed that there was no substantial change in the composition of the product as compared to (b).

The 4,5-dichloro-diimid-2-carboxylic acid N-formyl-amide of the following structural formula can be obtained by a similar method.

TABLE 4

Example 62

(a) From 4,5-dichloro-imidazole-2-carboxylic acid N-formyl-isopropyl amide (Example 51), 4,5-dichlor- imidazole-2-carboxylic acid N-form 25 g (0.1 mol) of mill-isopropylamine are stirred with 200 ml of concentrated sulfuric acid at 50-70 ° C. for 15 minutes. After cooling, the mixture was poured into ice, the product was filtered, washed with water until neutral and dried to 16 g of 4,5-dichloro-imidazole-2-carboxylic acid isopropylamide having a melting point of 150 ° C (72% of theory). ).

(b) From 4,5-dichloro-2-dichloromethylene-imidazolic acid (single container identification)

654 g (3 mol) of fine powdered 4,5-dichloro-2-dichlormethylene-imidazole was partially added to a mixture of 783 g (9 mol) of isopropyl formamide and 162 g (9 mol) of water with slight stirring. do. The reaction temperature at this time is raised to about 75 ℃. The reaction mixture is further heated to about 90 to 110 ° C. for 1/2 hour. After cooling, the product is precipitated in water, filtered, washed with water and dried to yield 566 g (85% of theory) of 4,5-dichloro-imidazole-2-carboxylic acid isopropylamide having a melting point of 150 ° C.

The 4,5-dichloro-imidazole-2-carboxylic acid amide of the following structural formula can be obtained by a similar method.

TABLE 5

Example 76

10 g (0.043 mol) of the cyclic reaction product of the formula

100 ml of concentrated sulfuric acid is reacted for about 5 minutes between 60 and 80 캜. After cooling, the mixture was poured into ice, the product was filtered, diluted with water until neutral and dried to give 6 g of 4,5-dichloro-imidazole-2-carboxylic acid ethylamide having a melting point of 146 ° C (67% of theory). To obtain.

The starting material of formula 76a used in Example 75 may be prepared by the following method. 21.8 g (0.1 mol) of fine powder 4,5-dichloro-2-dichlor-methylene-imidazole is added to 87 g (1 mol) of N-ethyl-acetamide with stirring. The temperature of the exothermic reaction at this time is raised to about 50 ° C. After cooling, the product was precipitated with water, filtered, washed with water and dried to give 14 g (60% of theory) of the bicyclic compound of formula 76a having a melting point of 155 ° C. Munic needle acicular crystals are obtained from hexane.

In a similar manner, N-methyl-acetamide may be used as a starting material to obtain a bicyclic compound having the following structure having a melting point of 194 ° C.

Similar to the above example, this compound is saponified with concentrated lead sulfate to give 4,5-dichloro-imidazole-2-carboxylic acid methyl amide. Melting Point 240 ° C (Example No. 64)

Example 77

Tricyclic compound 20 (0.087 mol) of the formula

The mixture of 100 ml of formic anhydride is heated under reflux for 2 hours. After cooling the mixture, the product was filtered, washed with water and dried to 19 g of 4,5-dichloro-imidazole-2-carboxylic acid 3-carboxy-n-propylamide having a melting point of 285 ° C. (82% of theory). ). Further 3 g of carboxylic acid is obtained when the formic acid filtrate is heated under reflux for 6 hours.

The tricyclic starting material is heated with 10 times sulfuric acid at 100 ° C. for 15 minutes, then the mixture is cooled, poured on ice and separated by conventional methods to give the same compound as above.

The 4,5-dichloro imidazole-2-carboxylic acid W-carboxy-n-alkylamide of the following structural formula can be obtained by a similar method.

TABLE 6

The tricyclic starting materials used in Examples 77-79 can be prepared by the following method.

21.8 g (0.1 mole) of fine powdered 4,5-dichloro-2-dichloromethylene-imidazole is added in small portions to a mixture of 25 g (0.3 mole) of pyridone and 125 ml of dioxane.

The reaction temperature at this time is raised to about 50 ℃.

The mixture is heated to about 90 ° C. in a short time, then cooled and poured into water. The product is filtered, washed with water and dried to give 17 g (74% of theory) of the tricyclic compound of the above formula having a melting point of 230 ° C.

The same compound is obtained when 4,5-dichloro-2-trichloromethyl-imidazole is used as starting material.

Structural formulas 78a (melting point: 230 ° C.) and structural formulas 79a (melting point: 168 ° C.) can be obtained in a similar manner using δ-valerolactam and ε-caprolactam as starting materials, respectively.

Example 80

21.8 g (0.1 mol) of 4,5-dichloro-2-trichloromethylene-imidazole solution was added to a solution of 15 g (0.11 mol) of N-methyl-benzamide in 100 ml of dioxane.

The next compound is heated to boiling point in a short time and added to ice water. The first precipitated oil becomes a solid after several hours. The product was filtered off, washed with water and dried to give 6.0 g of N-benzoyl-N-methyl-4,5-dichloro-imidazole-2-carboxylic acid amide having a melting point of 168 ° C. (in acetonitrile) (20% of theory). To obtain.

Example 81

21.8 g (0.1 mol) of 4,5-dichloro-2-trichloromethyl-imidazole are added to a suspension in which 15 g (0.25) of urea is dissolved in 100 ml of dioxane, and the mixture is heated to a boiling point in a short time while stirring.

After cooling, the mixture is poured into water, the product is filtered off, washed with water and dried to 18 g (67% of theory) of 4,5-dichloro-imidazole-2-oil-urea (crystallized with 1/2 mole of dioxane). To obtain. Melting Point:> 290 °

Crystalline dioxane can be removed in vacuo at about 140 ° C. and can also be removed by boiling in ethanol in a short time.

Substituted imidazoloyl ureas of the following structure can be obtained in a similar manner.

TABLE 7

Example 85

21.8 g (0.1 mol) of 4,5-dichloro-2-trichloromethylene-imidazole was added to a solution in which 26 g (0.22 mol) of N, N'-diethylurea was dissolved in 150 ml of water, followed by stirring at 100 ° C. Heat. After cooling, the product was filtered, washed with moles and dried to yield 18.5 g (66% of theory) of 4,5-dichloro-imidazole-2-oil-N, N-diethylurea having a melting point of 159 ° C.

1 part by weight of the reaction product was boiled with about 10 parts by weight of formic anhydride for 1 hour, the formic acid was removed under vacuum and the residue was recrystallized from acetonitrile to give a melting point of 146 ° C. (Example No. 6) 4,5- Dichloro-imidazole-2-carboxylic acid N-ethylamide is obtained in high yield.

Example 86

The compound is obtained by the same method as the procedure of Example No. 85. Melting Point 205 ° C. The reaction product is cleaved immediately upon attempting to recrystallize in boiling acetonitrile to give 4,5-dichloroimidazole-2-carboxylic acid N-methyl amide having a melting point of 240 ° C. (Example 64).

Example 87

21.1 g (0.1 mol) of 4,5-dichloro-imidazole-2-thiocarboxylic acid-S-methyl ester and a solution of 11 g (0.25 mol) of dimethylamine in 100 ml of mol are boiled under reflux for 3 hours. . The solution is filtered, cooled and acidified. The separated crystals are filtered, washed with water and dried to yield 9 g (43% of theory) of 4,5-dichloro-imidazole-2-carboxylic acid dimethyl amide. Melting point 244-246 ° C. (in toluene) (see Example 46)

Example 88

The gaseous dimethylamine was passed through a suspension of 10.0 g (0.0306 mol) of dimer ketone of the formula (IV) in 100 ml of dimethylformamide until a clear, virtually colorless solution was formed. Was evaporated to dryness in vacuo and the residue was recrystallized from chlorobenzene to give 11.5 g (90% of theory) of 4,5-dichloro-imidazole-2-carboxylic acid N, N-dimethylformamide having a melting point of 245 ° C. do.

The 4,5-dichloro-imidazole-2-carboxamide of the following structural formula can also be obtained by a method similar to the above.

TABLE 8

Example 106

Compounds of the following structure can also be obtained from ethylene diamine in a similar manner.

Melting Point: 290 ° C (In Ethanol)

Example 107

A solution of 10.0 g (0.306 mol) of dimer ketone of the formula (IV) in 100 ml of glycol was heated to about 150 ° C. until a clear solution was formed, and then excess glycol was removed under vacuum in a rotary evaporator to melt it. 13 g (14% of theory) of 4,5-dichloro-imidazole-2-carboxylic acid 2-hydroxyethyl ester at 170 ° C are obtained.

Colorless crystals are obtained from acetonitrile.

The dimer ketones used in Examples 88-107 can be prepared by the following method.

(a) 40 g (0.55 mol) of dimethylformamide is dissolved in 100 ml (0.46 mol) of 4,5-dechloro-2-dichloromethylene-imidazole in 1 L of petroleum ether (boiling point of about 60 DEG C) and boiled in about 10 Dropping over a minute separates the precipitate. After cooling, the petroleum ether was decanted, the precipitate was stirred with acetone, the product was filtered off, washed with acetone until the acetone used was pale yellow, and 41 g of the dimer ketone of the above formula (55% of theory) had a melting point> Obtained as a pale yellow powder at 290 ° C.

(b) A mixture of 500 g of 4,5-dichloroimidazole-2-carboxylic acid monohydrate (see Example No. 7 for its preparation) and 1.8 L of thionyl chloride is stirred at reflux for about 75 ° C. for 24 hours. After cooling, the product is filtered, washed with a small amount of thionyl chloride and then with petroleum ether and dried to give 362 g (89% of theory) of the dimer ketone of the above formula in the form of a pale yellow powder having a melting point of> 290 ° C. This is the same as the product prepared in (a).

Example 108

A solution of 20 g (0.225 mol) of carbamic acid ethyl ester and 21.8 g (0.1 mol) of 4,5-dichloro-2-dichloro-methyleneimidazole in 50 ml of dioxane was heated to boiling (about 115 ° C.) in a short time. do. After cooling, the product was precipitated with water, filtered, washed with water and dried to give 15 g of N- (4,5-dichloro imidazole-2-oil) -carbamic acid ethyl ester having a melting point of 208 ° C. (in acetonitrile). 60%) is obtained.

Example 109

N- (4,5-dichloro-imidazole-2-yl) -carbamic acid methyl ester having a melting point of 247 ° C. (in ethanol) is obtained by a similar method as in Example 108

Example 10

A solution of 21.8 g (0.1 mol) of 4,5-dichloro-2-dichloromethylene-imidazole in 20 ml of dioxane was dissolved in a suspension of 22 g (0.114 mol) of sodium salt of P-toluene-sulfonamide in 200 ml of water. After stirring, the mixture is heated to the boiling point in a short time and the product is filtered while the mixture remains at the boiling point. The precipitate is dried and recrystallized with acetonitrile or toluene to give 14 g (42% of theory) of N- (4-methylphenylsulfonyl) -4,5-dichloroimiazole-2-carboxylic acid amide having a melting point of 238 ° C.

Example 111

20.9 g (0.1 mol) of 4,5-dichloro-imidazole-2-carboxylic acid ethyl ester are added in small portions with stirring to a mixture of 15 g (0.3 mol) of hydrazine hydrate and 100 ml of ethanol at room temperature. Boiling for 2 hours and cooling the mixture precipitates the hydrazine salt of 4,5-dichloro-imidazole-2-carboxylic acid hydrazide. It is filtered, suspended in 100 ml of water, and diluted with sodium hydroxide solution to form a solution. The solution is acidified with acetic acid. The separated crystals are filtered, washed with water and dried to afford 11 g (56.5% of theory) of 4,5-dichloro-imidazole-2-carboxylic acid hydrazide. Melting Point 210 ° C. to 211 ° C. (ethanol)

Example 112

21.1 g (0.1 mol) of 4,5-dichloro-imidazole-2-thiocarboxylic acid S-methyl ester and 10.8 g (0.1 mol) of phenylhydrazine in 150 ml of ethanol are boiled together. The cooled reaction mixture was mixed with 500 ml of water, and the separated crystals were filtered, dried, and 4,5-dichloro-imidazole-2 carboxylic acid N′-phenyl-hydra having a melting point of 229 to 230 ° C. (in ethyl acetate). 13.5 g (50 ° C. of theory) of zayed are obtained.

Example 113

19.5 g (0.1 mol) of 4,5-dichloro-imidazole-2-carboxylic acid hydrazide and 7.2 g (0.1 mol) of isobutyraldehyde were boiled under reflux for 3 hours while adding 1 ml of concentrated hydrochloric acid in 150 ml of ethanol. The solvent is then distilled off to give 4,5-dichloro-imidazole-2-oil-isobutyirohydrazone in quantitative yield. Melting point 172-174 캜 (in toluene)

Example 114

The use of equimolar amounts of salicylic aldehyde instead of isobutyr aldehyde yields the corresponding hydrazone of the following structural formula.

Melting Point: 300 ° C (Glycol Monomethyl Ether)

Example 115

19.5 g (0.1 mol) of 4,5-dichloro-imidazole-2-carboxylic acid hydrazide and 10.1 g (0.1 mol) of triethylamine were added to 150 ml of dioxane, followed by 18.2 g of trichloro acetyl chloride (0.1 Mole) is added dropwise to the mixture with stirring at 10-15 ° C. The mixture was stirred at room temperature for at least 2 hours, 500 ml of water was added, and the separated crystals were filtered to give 26.2 g (77% of theory) of N- (4,5-dichloroimidazol-2-yl) -N´α´. Trichloroacetyl 'hydrazine is obtained. Melting Point 192-192 ℃ (Ethyl Acetate)

Example 116

Using animal equivalent of chloroformic acid ethyl ester instead of trichloroacetyl chloride, N ′-(4,5-dichloro-imidazole-2-oil) -carbazic acid ethyl ester of the following structural formula was obtained according to a method similar to the above. do.

Melting Point: 235 ~ 237 ℃ (butanol)

Example 117

(a) 19.5 g (0.1 mol) of 4,5-dichloro-imidazole-2-carboxylic acid hydrazide is dissolved in 150 ml of 5% strength hydrochloric acid solution. A solution of 7 g of sodium nitrite (0.1 moles of DIR) in a small amount of water is added dropwise at 0? 5 占 폚 with vigorous stirring. The mixture is stirred at the same temperature for at least 1 hour, filtered and the crystals are washed with water and dried at room temperature. The yield of 4,5-dichloro-imidazole-2-carboxylic acid azide is substantially quantitative. Mark the structure with spectra and mass spectra. This compound is heated at 175 ° C without melting.

(b) A solution of 218 g (1.0 mol) of 4,5-dichloro-2-dichloromethylene-imidazole in 250 ml of dioxane was dissolved in 80 ml (1.23 mol) of sodium azide in 1 L of water, Add dropwise over about 20 minutes between 10 and 30 ° C. The product is filtered, washed with water and dried to give 196 g (95% of theory) of the same 4,5-dichloro-imidazole-2-carboxylic acid azide as the product prepared in (a).

Example 118

25.45 g (0.1 mol) of 4,5-dichloro-2-trichloromethyl-imidazole is added in small portions at room temperature with vigorous stirring in a solution of 24 g (0.5 mol) of sodium hydroxide dissolved in 150 ml of methanol and saturated with hydrogen sulfide. The mixture is stirred at room temperature for at least 2 hours and further at 50 ° C. for 2 hours. The separated sodium chloride is filtered and 14.29 g (0.1 mol) of methyl iodide is added dropwise to the filtrate. The mixture is stirred for 1 hour more at room temperature, then for 1 hour at 40-45 ° C. and evaporated in vacuo. After dissolving camppumul in water, the solution was acidified and the separated crystals were filtered, washed with water and dried to give 19.7 g (80% of theory) of 4,5-dichloro-imidazole-2-dithiocarboxylic acid methyl. Obtain an ester. Melting Point: 122 to 124 ° C (Benzene for Cleaning)

Example 119

16.2 g (0.1 mol) of 4,5--dichloro-imidazole-2-carboxylic acid nitrile was dissolved in 125 ml of pyridine, 10.1 g (0.1 mol) of triethylamine was added, and anhydrous hydrogen sulfide was first passed at room temperature for 5 hours. Next check Raise the temperature to 50 ° C. The reaction mixture is evaporated in vacuo and the residue is taken up in water, the solution is acidified with hydrochloric acid and the precipitated crystals are filtered off. The crude product contains a small amount of atom and is recrystallized with dilute aqueous sodium hydroxide solution to liberate, filter and acidify again to give 16.2 g (82.5% of theory) of 4,5-dichloro-imidazole-2-thio-carboxylic acid. Obtain amide. Melting point 171-173 ° C. (in toluene)

Example 120

16.2 g (0.1 mol) of 4,5-dichloro-imidazole-2-carboxylic acid nitrile are suspended in 150 ml of methanol. Anhydrous hydrogen chloride is passed at 10-15 ° C. until the suspension is saturated. The insoluble material was filtered off and the filtrate was evaporated in vacuo and the residue was pressed onto clay and dried in a dasher on KOH to give 13 g (56.5% of theory) of 4,5-dichloro-imidazole-2-iminokar. Acid methyl ester hydrochloride is obtained. Melting Point: 250 ℃

Example 121

21.8 g (0.1 mol) of 4,5-dichloro-2-dichloromethylene-imidazole was added to 73 g (0.5 mol) of 50% strength aqueous tert-burylamine while stirring, and the reaction mixture was then heated to about 80 ° C. After cooling, the product was precipitated in water, filtered, washed with water and dried to give 24 g of 4,5-dichloro-imidazole-2-capric acid N, N'-tert-burylamine (80% of theory). This product is a dense pale yellow crystal with a melting point of 169 ° C. (in ethanol / water).

4,5-Dichloro-imidazole-2-carboxylic acid amidine of the following structural formula can be obtained by a similar method.

TABLE 9

Example 125

A mixture of 18.8 g (0.2 mol) of α-amino-pyridine was cooled in a solution of 25.4 g (0.1 mol) of 4,5-dichloro-2-trichloromethyl-imidazole in 200 ml of dioxane while cooling at 10 to 15 ° C. Add it down. The mixture is stirred at room temperature for at least 2 hours and 1 liter of water is added to make the resulting mixture slightly acidic with acetic acid. The separated crystals were filtered off, washed with water and dried to give 25.3 g of 4,5-dichloro-imidazole-carboxylic acid N, N'-di-pyrid-2-yl-amidine (77% of theory). To obtain. Melting point 199 to 200 ° C (from ethyl acetate ligroin)

C ₁₄ H ₁ 0Cl ₂ N ₆ (333.2) calculated: 21.3% Cl. 25.24% N

Found: 20.8%, 25%

Example 126

16.2 (0.1 mol) of 4,5-dichloro-imidazole-2-carboxylic acid natrile is suspended in 120 ml of ethanol. 8 g (0.115 mole) of hydroxyl ammonium chloride is added and 14 g of calcium carbonate are added in small portions. The mixture is heated to the boiling point and boiled until no more CO ₂ gas is released. Components such as salts are filtered off and washed with ethanol and the filtrate is evaporated in vacuo. The residue is recrystallized from ethyl acetate to give 12.2 g (63% of theory) of 4,5-dichloro-imidazole-2-carbamide-oxime. Melting Point 270-275 ℃

C ₄ H ₄ Cl ₂ N ₄ O (195.0) Calculated: 36.36% Cl, 28.74% N

Found: 36.9 28.3

Example 127

19.5 g (0.1 mol) of 4,5-dichloro-imidazole-2-carbamide-oxime and 10.1 g (0.1 mol) of triethylamine are dissolved in 150 ml of dioxane. 14.05 g (0.1 mol) of benzoyl chloride is added dropwise to this solution at 15 to 20 ° C. The mixture is stirred at room temperature for at least 1 hour and at 50 ° C for 2 hours, and then added to 500 ml of water. The separated crystalline is filtered, washed with water and dried to give 18 g (60.2% of theory) of 4,5-dichloro-imidazole-2-carbamide-O-benzoyl-oxime. Melting point 177-178 degreeC (from toluene)

Example 128

시간 이상 교반시킨다. 불용성 성분을 여과 제거하고 여액을 진공중에서 증발시킨다. 결합된 잔류물을 뜨거운 물에 용해시킨다. 반응생성물은 묽은 염산으로 산성화됨에 따라서 침전된다. 이 생성물을 여과하고 물로 세척하여 건조시킨다.25.4 g (0.1 mol) of 4,5-dichloro-2-trichloromethyl-imidazole was added to a small amount of vigorous stirring with cooling on 200 ml of ethanol saturated with ammonia. Mixture DFM at 50 ℃

Stir for at least hour. Insoluble components are filtered off and the filtrate is evaporated in vacuo. The combined residue is dissolved in hot water. The reaction product precipitates as it is acidified with dilute hydrochloric acid. This product is filtered off, washed with water and dried.

Yield: 14.6 g (90% of theory) Melting point: 187 to 189 ° C (from toluene)

Example 129

10.9 g (0.1 mol) of 2-aminophenol and 40.4 g (0.4 mol) of triethylamine are dissolved in 200 ml of dioxane. 25.4 g (0.1 mol) of 4,5-dichloro-2-trichloromethyl-imidazole are added little by little while cooling to 15-20 degreeC. The mixture was stirred at room temperature for at least 1/2 hour and at 60-70 ° C. for 2 hours. The reaction mixture is then added to 1 L of water, acidified with diluted hydrochloric acid and the precipitate is filtered off. It is washed with water and dried to give 12 g (47.2% of theory) of 2- (4,5-dichloro-imidazol-2-yl) -benzoxazole. Melting point 196-198 ° C (from ethanol)

Example 130

In the same process, using 10.8 g (0.1 mol) of phenylenediamine instead of 2-aminophenyl, 2- (4,5-dichloro-imidazol-2-yl) benzimidazole of the following structural formula [melting point: 300 ° C ( From butanol).

Example 131

In a similar manner, 6 g (0.1 mole) of ethylenediamine in place of 2-aminophenol was used to form 2- (4,5-dichloro-imidazol-2-yl) -imidazoline [melting point 260 ° C. (ethyl acetate) Ligroin)].

Example 132

21.8 g (0.1 mol) of 4,5-dichloro-2-dichloromethylene-imidazole was added to 300 ml of dioxane and 3,4-dichloro-isothiazole-5-carboxylic acid hydrazide (melting point: 156 ° C; 3, 23.5 g (0.11 mol) of 4-dichloro-isothiazole-5-carboxylic acid prepared by the conventional method described in US Pat. No. 3,341,547 are added to the dissolved solution with stirring.

The reaction mixture is warmed to about 50 ° C. and at the same time a large volumetric charge is separated. After brief heating to 100 ° C., the mixture is cooled, the precipitate is filtered off, washed with dioxane and dried. In this way, 33 g (84% of theory) of the experimental C ₈ H ₂ Cl ₅ N ₅ OS and intermediate product which is one of the tautomers of the following structural formula are obtained.

The intermediate is dissolved at 205 ° C. while releasing HCl and then solidified again. It is converted to an oxidazole derivative of the above structural formula, which is dissolved at 226 ° C. during this process.

The same oxidazole derivatives are used in place of dioxane when reacting at temperatures from 200 to 250 ° C. in high boiling solvents such as 1,2,4-trichlorobenzene or 1-chloronaphthalene, "One pot process".

The imidazole ox diazoles of the following structural formula can be obtained in a similar manner.

TABLE 10

Example 137

To a solution of 25.4 g (0.1 mol) of 4,5-dichloro-2-drichloromethyl-imidazole in which 16.7 G (0.11 mol 0) of carbazic acid phenyl ester was dissolved in 200 ml of dioxane was added in small portions at room temperature. After the reaction is completed, the mixture is gradually heated to the boiling point and boiled under reflux for at least 2 hours, it is cooled at room temperature and 20.2 g (0.2 mol) of triethylamine are added dropwise The mixture is stirred at 50 ° C. for at least 2 hours and the insoluble components are After filtration, the filtrate is evaporated under vacuum The residue is treated with water, the product is filtered off, washed with water and dried to give 2- (4,5-dichloro-imidazol-2-yl) -5-phenoxy-1 21.5 g (72.5% of theory) of 3,4-oxadiazole are obtained.

Melting Point: 109 ° C (from Toluene)

Example 138

9.1 g (0.1 mole) of thiosemi carbazide and 40.4 g (0.4 mole) of triethylamine are added to 200 ml of ethanol until a clear solution is formed and stirred. 25.4 g (0.1 mol) of 4,5-dichloro-2-trichloromethyl-imidazole are added to the solution in small portions at 0 to 5 ° C while stirring. The mixture is stirred for 1 hour or more while cooling, and stirred at room temperature for 1 hour at 50 ° C for 1 hour. After cooling the amine-hydrochloride is filtered off and the filtrate is evaporated in vacuo. The residue is treated with water, the mixture is acidified with hydrochloric acid, the product is filtered off, washed with water and dried to give 2- (4,5-dichloro-imidazol-2-yl) -5-amino-1,3,4-thia 18 g (76.5% of theory) of sol are obtained.

Melting point: 147 ° C. (decomposition) (from ethyl acetate ligroin)

Example 139

In the same process, 3- (4,5-dichloroimidazol-2-yl)-in the following structure using semicarbazide-hydrochloride in place of thiosemicarbazide in the presence of a 5-fold molar amount of triethyl amine 1,2,4-triazol-5-one is obtained.

Melting point: 176 to 178 ° C (from ethyl acetate ligoin)

Example 140

19.6 g (0.1 mol) of 4,5-dichloro-imidazole-2-thiocarboxylic acid amide and 15.5 g 90.1 mol of W-chloro-acetophenone) are dissolved in 200 ml of acetonitrile.

30 g of calcium carbonate are added and the mixture is gradually heated to the boiling point. After boiling for 5 hours, the insoluble components are filtered off and the filtrate is evaporated in vacuo. Combined residue is added to water. Hydrochloric acid is then added until a weak acid reaction is obtained. The insoluble material is filtered off, washed with water and dried. Yield: 18 g (16% of theory; melting point 159 to 160 ° C. (from washing benzene)

Example 141

In the same manner as in Example 118, 2- (4,5-dichloro-imidazol-2-yl (-4-tert-butyl-) using bromopinacholine (17.9 g) instead of chloro-acetphenone was used. 21 g (76% of theory) of thiazole are obtained.

Melting point 157-158 ° C. (from washing benzine)

Example 142

16.2 g (0.1 mol) of 4,5-dichloro-imidazole-2-carboxylic acid nitrile are dissolved in 150 ml of ethanol while warming. To this solution is added a solution of 2.3 g (0.1 mol) of sodium dissolved in a small amount of ethanol. After brief stirring the solution is evaporated in vacuo. Water soluble sodium salt is obtained in high yield. Melting Point: ＞ 250 ℃

Example 143

22.3 g (0.1 mol) of 4,5-dichloro-imidazole-2-carboxylic acid isopropyl ester are dissolved in 150 ml of toluene while warming the liver. To this solution was added 10.1 g (0.1 mol) of triethylamine.

The mixture is stirred at room temperature for 1/2 hour, cooled to 0 ° C. and the crystalline product is filtered off and dried to give a water soluble triethyl ammonium salt in high yield. Melting Point:> 250 ℃

[Examples 144 to 150]

16.2 g (0.1 mol) of 4,5-dichloro-imidazole-2-carboxylic acid natril is dissolved in 150 ml of ethanol. To this solution is added 0.1 mole of amine and then the solvent is evaporated off in vacuo to give the amine salt as a high yield residue.

Example 151

16.2 g (0.1 mol) of 2,5-dichloroaniline and 10.1 g (0.1 mol) of triethylamine were dissolved in 10.9 g (0.05 mol) of 4,5-dichloro-2-dichloro-methylene-imidazole in 50 ml of dioxane. The solution is added at about 20 ° C. The mixture was then simply heated to about 100 ° C. and cooled, then the product was precipitated in water, filtered, washed with water and dried to give 4,5-dichloro-imidazole-2-carboxylic acid N, N-di- (2, 22 g (94% of theory) of 5-dichlorophenyl) amidine are obtained. Melting point 212 degrees Celsius (from toluene)

4,5-Dichloro-imidazole-2-carboxylic acid N, N-diarylamidine of the following structural formula can be obtained by a similar method.

TABLE 11

Example 174

16.3 g (0.05 mole) of a dimer ketone of the formula (IV) dissolved in 100 ml of dimethylformamide was mixed with 14 g (0.11 mole) of 2,4-difluoroaniline. The solution is formed by heating to 145-155 ° C. for 5 minutes. After cooling, the product was precipitated in water, filtered, washed with water and dried to give 24 g of 4,5-dichloro-imidazole-2-carboxylic acid N- (2,4-difluorophenyl) -amide (83 of theory). %) Is obtained.

Melting Point 290 ° C (O-dichlorobenzene)

Example 175

21.8 g (0.1 mol) of fine powdered 4,5-dichloro-2-dichloromethylene-imidazole, 16 g (0.125 mol) of 2-chloro-aniline, fine powder, 100 ml of water and 15 g of 37% strength hydrochloric acid solution (about 0.15) Molar) is added at room temperature with stirring and the mixture is heated at about 100 < 0 > C for 1 hour. After cooling the solution, the product was filtered, washed with water and dried to give 21.5 g (75% of theory) of 4,5-dichloro imidazole-2-carboxylic acid 2-dichloro-anilide having a melting point of 244 ° C. This material is crystallized colorless to benzene or 1,2-dichlorobenzene. The same compound can be obtained using 4,5-dichloro-2-trichloromethyl-imidazole as starting material.

In the same manner as in the above two examples, 4,5-dichloro-imidazole-2-carboxylic acid anilide of the following structural formula can be obtained.

TABLE 12

Example 215

A solution of 109 g (0.5 mol) of 4,5-dichloro-2-dichloroethylene-imidazole in 125 ml of dioxane was added to a mixture of 500 ml of fine powder of 2,6-dichloroaniline, 500 ml of water, and 75 g of 37% aqueous hydrochloric acid solution, ranging from 55 to 55. Add dropwise over about 10-15 minutes with stirring at 60 ° C. After stirring for about 2 hours, the product was filtered, washed with water and dried to give 4,5-dichloro-imidazole-2-carboxylic acid N- (2,6-dichlorophenyl) -imide-chloride 159 g 9 theory of 72 %) Is obtained. The long needle at melting point 200 ° C is crystallized from acetonitrile or chloroform.

The 4,5-dichloro-imidazole-2-carboxylic acid N-aryl-imidechloride of the following structure can be obtained by a similar method.

TABLE 13

Example 217

25 g (0.73 mol) of 4,5-dichloro-imidazole-2-carboxylic acid N- (2,6-dichlorophenyl) -amide-chloride (refer to Example 215 for recipe) with 125 g of concentrated sulfuric acid for about 5 hours Stir. The mixture is placed on ice and the product is filtered off, washed with water until neutral and dried to give 18.5 g (78% of theory) of 4,5-dichloro-imidazole-2-carboxylic acid 2,6-dichloro anilide. .

Melting point 206 ° C (from acetonitrile)

Example 218

34.4 g (0.1 mol) of fine powdered 4,5-dichloro-imidazole-2-carboxylic acid N- (26, -diclophenyl) -imide-chloride (see Example 215) in 500 ml of water 19 g (0.12 mol) of 3-trifluoromethyl-aniline are added to the dissolved solution and the mixture is heated with stirring at 100 ° C. for 5-10 minutes. After cooling the resulting product was washed with water and dried to give 4,5-dichloro-imidazole-2-carboxylic acid N- (2,6-dichlorophenyl) -N '-(3-trifluoromethylphenyl)- 46 g (98% of theory) of amidine are obtained.

Amidine of the following structural formula can be obtained by a similar method.

TABLE 14

Example 232

20 g (0.06 mol) of fine powdered 4,5-dichloro-amidazole-2-carboxylic acid N- (2,6-dichlorophenyl) imide-chloride (see Example No. 215) was stirred in concentrated ammonia solution. While adding. After further stirring for 1 hour the product was filtered, washed with water and dried to give 15 g of 4,5-dichloro-imidazole-2-carboxylic acid N- (2,6-dichlorophenyl) -amidine (77% of theory). ). Melting point 270 ° C. (from acetonitrile)

Example 233

4, -5-dichloro-imidazole-2-carboxylic acid N- (2,6-dichlorophenyl) -imide-chloride (Example No. 216) 17.2 in which 7.5 g of dialrylamine was dissolved in 200 ml of dioxane It is added to g (0.05 mol) solution at 20-30 degreeC.

After further stirring for 1 hour, the product is precipitated in water, neutralized with dilute hydrochloric acid, filtered, washed with water and dried to give 4,5-dichloro-imidayl-2-carboxylic acid N- (2,6-dichloro- 18.5 g (97% of theory) of phenyl) -N ', N'-diethyl-amidine are obtained.

Melting point 175 ° C. (from acetonitrile)

Example 234

34.4 g (0.1 mol) of fine powdered 4,5-dichloro-imidazole-2-carboxylic acid N- (2,6-dichlorophenyl) -imide chloride (see Example 215) in 400 ml of methanol After further stirring at a solution of 10 g (0.18 mol) of dissolved calium hydroxide at 20 ° C. for about 1 hour, the product was precipitated in water, neutralized with dilute hydrochloric acid, filtered, washed with water and dried to give 4,5-dichloro- 26 g (77% of theory) of imidazole-2-carboxylic acid (2,6-dichlorophenylimido) -methyl ester are obtained. Melting point: 203 ° C (from benzene)

Example 235

17.2 g (0.05 mol) of fine powdered 4,5-dichloro-imidazole-2-carboxylic acid N- (2,6-dichlorophenyl) -imide chloride (see Example No. 215) for 200 ml of water To a solution of 9 g (0.062 mol) of 4-chloro-thiophenol and 4 g (0.071 mol) of potassium hydroxide dissolved in the solution was added with stirring at 20 to 25 ° C. After further stirring at 20-25 ° C. for 5 hours, the product was filtered, washed with water and dried to give 4,5-dichloro-imidazole-2-carboxylic acid (2,6-dichlorophenyl-imido)-(4- Chlorophenyl) thioester 18 g (80% of theory) are obtained. Melting point 190 ° C. (from small amount of acetonitrile)

[Examples 236 to 238]

The following compounds can be prepared by the same process as described in Example 142.

TABLE 15

Claims (1)

4,5-dichloro-2-dichloromethyl imidazole of formula (II) is reacted with a nucleophilic reagent of formula HZ to form a 4,5-dichloro-imidazole-2-carboxylic acid derivative of formula (I) How to prepare a salt.

In the above structural formula

Represents a carbon atom having three bonds with a heteroatom, and Z represents a halogen, an azide group or -O-R¹⁰Or -O-R¹⁰R represents a group¹⁰Silver hydrogen, metal cations or -NR₄ ⁺As a cation wherein R represents hydrogen or an alkyl, aryl, cycloalkyl or aralkyl group and two or three R moieties form a 5- or 6-membered ring and R¹⁰Silver c_One-₁₈-Alkyl or C₃-₁₂Alkenyls [any of which may be optionally substituted with chlorine, fluorine, bromine, acyloxy, wherein acyl is an aliphatic, cycloaliphatic or aromatic carboxylic acid or

Flag, C_One-₄Alkoxy, C_One-₄-Alkoxy-C_One-₄Alkoxy, phenoxy or naphthoxy (whichever is optionally halogen, C_One-₄-Alkyl, CF₃Or NO₂Arylmercapto, arylsulfonyl or arylsulfonyl (any of which is C)_One-₄-May be substituted with alkyl or halogen), C_One-₄Alkylsulfonyl, acylamino or diacylamino, where acyl represents an aliphatic, substituted, araliphatic, aromatic or heterocyclic carboxylic acid or carboxylic acid or thiocarboxylic acid derivative), CN, carboxylic ester group, C 5 to C 5 Cycloalkyl having 6 rings, phenyl (optionally halogen, C_One-₄-Alkyl or C_One-₄-Substituted by alkoxy) or 5- or 6-membered heterocycle] C₃-₁₂Alkynyl, cycloalkyl having a ring of 3 to 6 carbon atoms (optionally halogen, C_One-₄-Alkoxy or C_One-₄-Alkyl) or phenyl or naphthyl [these are optionally C_One-₄-Alkyl, polyhalogenoalkyl of 1 to 4 carbon atoms, halogen, C_One-₄-Alkoxy phenoxy or phenylmercapto, which are optionally halogen, C_1-4Alkyl, CF₃, C_1-4Alkoxy or NO₂May be substituted) C_One-₄Alkyl mercapto, C_One-₄Alkylsulfonyl, alkoxycarbonyl, aminocarbonyl, CN, NO₂Or mono- or dialkyl amino having 1 to 4 carbon atoms for each alkyl group, or Z is

Represents a group of where R¹¹And R¹²Are the same or different and each hydrogen, C_One-₁₂-Alkyl or C₃-₈Alkenyl [these are optionally chlorine, bromine fluorine, OH, C_One-₄Alkoxy, phenoxy (this is optionally C_One-₄Alkyl, halogen or C_One-₄-May be substituted with alkoxy), acyloxy group

C_One-₄-Alkylmercapto (optionally substituted with phenyl), phenylmercapto (optionally halogen or C_One-₄Alkyl), -CN, -COOH, -CONH₂, -CONH (C_One-₄-Alkyl), -CON (C_One-₄-Alkyl)₂, -CONH-aryl or aryl (aryl groups are optionally halogen, C_One-₄-Alkyl, CF₃, C_One-₄-Alkoxy or NO₂Phenyl or naphthyl), cyclopentyl, cyclohexyl, 5- or 6-membered heterocycle, or

Group where R¹¹Represents one of the aforementioned groups.] C₃-₁₂Alkynyl (optionally substituted with phenyl, cyclohexyl or cyclopentyl), C₄-₈Cycloalkyl (optionally alkyl or CF₃Or aryl, preferably phenyl, or napryl, these are C_One-₄Alkyl, C_One-₄-Halogenoalkyl, halogen, C_One-₄-Alkoxy, acetyl, aryloxy or arylpercapto (halogen, C_One-₄-Alkyl, CF₃, C_One-₄Alkoxy or C_One-₄Alkylmercapto may be substituted) C_One-₄Alkyl mercapto, C_One-₄Alkylsulfonyl, alkoxycarbonyl, aminocarbonyl, CN NO₂Mono-C_One-₄-Alkylamino, di (C_One-₄Alkyl) amino, C_One-₄-Form a multi-ring containing one or more heteroatoms such as halogenoalkyl mercapto or S, O and N, or R¹²Is OH, C_One-₄Alkoxy (optionally substituted with phenyl) or structural formula

Represents an acyl group of R¹³Silver hydrogen, C_1-12Alkyl or C_2-8Alkenyl [these are optionally halogen, C_One-₄Alkoxy, phenoxy (which is optionally halogen, methyl or NO₂Substituted by), C_One-₄Alkyl mercapto, phenyl mercapto (which is optionally substituted with halogen or methyl), or phenyl (which is optionally halogen or C)_One-₄Substituted with alkyl), and the like] C_2-8Alkynyl, cycloalkyl having 3 to 8 carbon atoms, phenyl or naphthyl (any of which is optionally halogen C_One-₄Alkoxy, C_One-₄Alkyl CF₃Or NO₂Or a 5- or 6-membered heterocycle containing a hetero atom such as O, S or N, and R¹²Is a structural formula

Represents a group of where R¹⁴C_1-12Alkyl, C_One-₄Alkenyl or C₃-₁₂Alkynyl [these are each optionally halogen, C_One-₄Alkoxy, phenyl (optionally itself halogen or C_One-₄Substituted with an alkyl) cycloalkyl having a ring of 5 or 6 carbon atoms containing O, S or N. Cycloalkyl having a ring of 5 or 6 carbon atoms (optionally C_One-₄Substituted with alkyl) or phenyl or naphthyl (either of which is optionally halogen, C_One-₄Alkyl, CF₃, C_One-₄Alkoxy, C_One-₄Alkyl mercapto, NO₂Or substituted with CN) or R¹²constitutional formula

Group, where R¹⁵Are the same or different and hydrogen, C_One-₁₂Alkyl or C₃-₈Alkenyl (any of these optionally halogen, C_One-₃Alkyl, CF₃, C_One-₄-Substituted by alkoxy), phenyl (optionally halogen C_One-₄Alkoxy, C_One-₄Alkyl mercapto or NO₂), Cycloalkyl or -SO with 5 or 6 carbon atoms₂-R⁸Represents a sulfonyl group of⁸Silver c_One-₁₂Alkyl (optionally substituted by chlorine or fluorine), phenyl (optionally chlorine, C_One-₄Alkyl, C_One-₄Alkoxy, CF₃Or NO₂Or a secondary amine group or R¹²Is a structural formula

Represents a group of where R⁷Wow R⁶Is hydrogen or C as the same or different group._One-₄Alkyl (this is optionally halogen or C_One-₄Or phenyl optionally substituted with alkyl), phenyl (optionally halogen, NO₂, C_One-₄Alkyl, C_One-₄Alkoxy or CF₃Substituted by) or a structural formula

Represents a group of where R⁷Silver hydrogen C_One-₁₂Alkyl or C₂-₈Alkenyl [any of these is halogen, nitro, C_One-₄Alkyl mercapto, phenyl mercapto (optionally halogen or C_One-₄-Substituted with alkyl), phenyl (optionally halogen or C)_One-₄-Or substituted by cycloalkyl having a ring of 5 or 6 carbon atoms;₂-₈Alkynyl, cycloalkyl having 3 to 6 carbon atoms, phenyl or naphthyl (both of which are optionally halogen C_One-₄Alkyl, C_One-₄-Alkoxy CF₃Or NO₂Substituted by), 5- or 6-membered heterocycle containing O, S or N as a hetero atom or a structural formula -OR²⁶Or -SR²⁶Represents a group of where R²⁶Silver c_One-₁₂Alkyl, C₃-₁₂Alkynyl [both of which are optionally halogen, C_One-₄-Alkoxy, phenyl (this is halogen or C_One-₄May be substituted with alkyl), cyclohexyl, furyl, thienyl or pyridyl], C₃-₆Cycloalkyl, or phenyl or naphthyl (any of these optionally halogen, C_One-₄Alkyl, C_One-₄-Alkoxy or nitro); or R⁷Silver r^{27 ′}-N-R²⁷Represents a group of where R²⁷Silver sites are the same or different, hydrogen, C_1-12Alkyl or C_3-8Alkenyl (any of these optionally halogen, C_1-4Alkyl C_1-4Alkoxy, C_1-4Alkyl mercapto, CF₃Or NO₂Can be substituted by) or R⁵And / or R⁶-OS₂-R⁸Represents a group where R⁸Is the same as above or R⁵R⁶Structural formula with autumn

Represents a group of where R⁹Are the same or different groups, each C_1-12Alkyl (optionally OH, C_1-4Alkoxy, COOH or COO (C_1-4Alkyl)), cycloalkyl having 5 or 6 carbon atoms, phenylalkyl or naphthylalkyl having 1 to 4 carbon atoms at the alkyl site (the phenyl or naphthyl moiety is optionally halogen, NO₂C_1-4Alkyl or C_1-4Substituted by alkoxy), phenyl or naphthyl (either of which is optionally OH, halogen, NO_2,C_1-4Alkyl, C_1-4Alkoxy, C_1-4Alkyl mercapto or CF₃Or a 5- or 6-heterocycle including O, S or N as a hetero atom, or both R⁹Form a carbocyclic ring or a heterocyclic ring with adjacent carbon atoms, or R⁹Either represents hydrogen, or R⁵And R⁶Together with adjacent N atoms can form a 5- or 6-membered heterocycle containing O, S or N as a hetero atom.