DE1670750A1 - Process for the preparation of substituted imidazopyridines - Google Patents

Description

PATENT LAWYERS

dr. w. Schalk dipl.-ing. P. Wirth dipl.-ing. G. Dan ν en be rc

DR.V.SCHMIED-KOWARZIK - DR. P.WEINHOLD DR. D. GUDEL

6 FRANKFURT AM MAIN

GK. ESCHENHEIME «STRAfSC 39

B.A. 16 149/65

Fisons Pest Control Limited Hareton, Cambridgeshire England

Process for the preparation of substituted imidazopyridines

(Elimination from P 48 939 IVd / 12 p)

The present invention relates to the production of substi tuated imidazopyridines with physiological effectiveness.

The substituted imidazopyridines (or their salts and functional derivatives of the same) have the formula

10981072185

in which one of the groups Z ¹ , Z ² , 7? and Z ^ a nitrogen f-

2. ^{r represents} 6 atoms and the other three groups represent CR, CR and CR ^, and R represents hydrogen, an alkyl group {e.g. with 1-4 carbon atoms, such as methyl or ethyl group), a substituted alkyl group (e.g. benzyl or Chlorobenzyl group), an aryl or substituted aryl group (e.g. chlorophenyl group) and -CYZR or -COR, where Y and Z are oxygen or sulfur and R is an alkyl group (e.g. with 1-6 carbon atoms, such as methyl, ethyl or propyl), a substituted one Alkyl group (e.g. chloromethyl or bromethyl group), an aryl group (e.g. phenyl or naphthyl group) or substituted aryl group (e.g. tolyl or xylyl group), and R, R ^ and R ^{4 are the} same or different and represent hydrogen, alkyl groups (e.g. with 1-6 carbon atoms * such as methyl, ethyl or propyl groups), hydroxy - ',' alkoxy, (e.g. methoxy, ethoxy or butoxy groups), substituted alkoxy, aryloxy (e.g. phenoxy groups), substituted aryloxy (e.g. chlorophenoxy groups) _t ifitro groups, halogens enes (e.g. chlorine, bromine or fluorine), pseudohalogens (e.g. cyano · * ·, iOhiocyan, isothiocyan or azido groups), substituted alkyl (ζ "Β. Trifluoromethyl, chloromethyl, bromoethyl, trichloromethyl, hydroxymethyl, 2-chloroethyl, 2-hydroxyethyl or 2-. · Methoxyethyl groups), carboxy groups, ester, amide, F-substituted or di-substituted amide, amino, mono- or di-substituted amino groups (e.g. methylamino, dimethylamino, acetylamino, trlfluoroacetylaraino-, benzenesulfonamido, p -iDoluenesulfonamide, methanesulfonamido) thiol, alkylthiol groups or their oxygen-containing derivatives (e.g. -SOR ⁶ or -SOgR ⁶ , where R ^{6 represents} an alkyl group) sulfonic acid and their ester or amide and substituted amide groups (e.g. phenylsulfamyl, ethylsulfamyl -, chloroethyl sulfamyl group) or a heterocyclic ring bonded to the imidazopyridine system via a nitrogen atom

BATH

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and X is a trifluoromethyl or pentafluoroethyl group represents. In one embodiment of the present invention Z ^ is the nitrogen atom * To functional derivatives of the substituted imidazopyxidines include, for example, the Jtf oxides.

A preferred embodiment of the present invention concerns imidazopyridines of the formula:

O G- IL

Il> - »

CC W

-11

in which R ^{11 is} hydrogen or -GOOR ¹ ^ (where R ^{15 is} an alkyl group, for example with 1 - 6 carbon atoms, such as methyl, ethyl or a phenyl group) and

R ¹ - ² , R ¹ ^ and R ¹ ^ for hydrogen, an .Alkylgruppe (for example with 1-6 carbon atoms, such as methyl, ethyl or butyl group) or for a halogen (for example chlorine, bromine or fluorine) .

In a particularly preferred embodiment of the invention the imidazopyridine is 6-chloro-2-trifluoromethylimidazo- (4,5-b) pyridine or its 1 (3) -phenoxycarbonyl derivative.

Salts of the substituted imidazopyridines according to the invention, in which R stands for hydrogen, (optionally quaternary) ammonium salts, metal salts, such as sodium, Potassium, calcium, zinc, copper and magnesium salts and amine salts, such as methylamine, ethylamine, dimethylamine, triethyl

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amine, ethanolamine, triethanolamine and benzylarain salts be. In a "preferred embodiment of the invention the salts are alkali salts. In general, the alkali salts are crystalline, easily soluble in water, pesticides.

The substituted imidazopyridines according to the invention can by reacting a 2,3-diaminopyridine or 3,4-diaminopyridine with trifluoroacetic acid or pentafluoropropionic acid or their functional derivatives, such as the acid chlorides or the amides.

In the case of the reaction with trifluoroacetic acid, this reaction can being represented by the following general formula

TT C - NH ₂

· '+ CF ₃ COOH
3 c-_NH

It can also be a salt of the diamine formula

CLOCK"

with a trihaloacetic acid or a functional Derivative thereof can be reacted in a medium composed of a halide of an inorganic acid. As an inorganic one

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Halide, any liquid inorganic halide such as phosphorus oxychloride, phosphorus trichloride, thionyl chloride and the like can be used. Phosphorus oxychloride is preferably used. The reactants are expediently refluxed together. When the product obtained is a trichloromethyl derivative, it can easily be converted to the corresponding irifluoromethyl derivative by treatment with a metal fluoride such as antimony fluoride.

The substituted imidazopyridines according to the invention, in which R represents the group -COOR ^, can by reaction the corresponding compound in which R is hydrogen, with a chloroformate R ^ OCOCl in the presence a base such as triethylamine. These substituted imidazopyridines can also be reacted an alkali salt of the corresponding imidazopyridine derivative be made with a chloroformate.

2 "3 4. When one of the groups R, R or R is a carboxyl group should, the compound can easily by oxidation of the corresponding Compound in which R, R3 or R. is a methyl group, e.g. with potassium permanganate.

The salts can be converted into aqueous or aqueous-organic solution or suspension with an alkaline compound of the metal, such as the Hydroxyd, or made with the Araln. ' The metal salts can also be produced by methathesis e.g. between the alkali salt of imidazopyridine and a salt of the metal will. Some imidazopyridines are also basic and can form salts with strong acids such as hydrochloric acid.

The substituted imidazopyridines according to the invention have physiological effectiveness. Are these compounds particularly useful as herbicides? however, they can also be found as

167075Q

■ - 6 -

Insecticides, molluscicides or fungicides use. Some of the compounds show, for example, "effectiveness against house flies, Mosquitoes and leaf spider mites.

The substituted imidazopyridines turned out to be special valuable as selective herbicides for use prior to sprouting and are also useful as treating agents after protruding · By some. Cultivation prod ucts the former type of treatment is of greater importance medium can be used.

Many of the salts of the substituted imidazopyridines of the invention are water-soluble and can be used in physiologically active preparations, e.g. in herbicides ,,. as aqueous solutions with or without wetting or dispersing agents, organic Solvents, adhesives and the like, which are usually spray media incorporated for agricultural and allied purposes will be applied, but in general it will it is preferred to use the salts of the substituted imidazopyridines, possibly in conjunction with a wetting agent.

fc The substituted imidazopyridines or their salts can possibly in a solvent immiscible with * water, such as. be dissolved in a high-boiling hydrocarbon, which appropriately contains dissolved emulsifying agents, so that when added to water it is considered self-emulsifiable oil works.

The substituted imidazopyridines or their salts can also with a wetting agent with or without an inert diluent to form a wettable powder that is soluble or dispersible in water, mixed, or they can be mixed with the inert diluent to form a solid or powdered product will. ,

BAD ORiGIMAi

- ■ 10981H / 2186 -

The new connections can also be shared with others physiologically active materials such as herbicides, insecticides, fungicides and molluscicides can be used. It has been found that when blended with other herbicides special advantages are obtained.

The following examples serve to illustrate the invention. Partial and, percentages relate if unless otherwise stated, based on weight.

At game 1 1

A solution of 1,000 parts of 2,3-diaminopyridine in 50 parts of trifluoroacetic acid was heated to reflux for 6 hours, cooled, poured into ice water and a sufficient amount of alkali was added to precipitate a brown solid. The Peststoff mirde filtered off, dried and 15 minutes heated above its Schmelzpunkt.von 150 ⁰ C, after which it again erstarren.ließ "The product was washed with water and dried to give 4" 9 ropes 2-trifluoromethylimidazo (4,5- b) pyridine as a white crystalline received at 245 ⁰ C sublimating Peststoff.

Analysis found: C, 44.78; , H. 2.45; S $ 22.21 >''

(C ₇ H ₄ E ₃ Kr ₃ ) Calculated: C 44.931 H 2.16; F 22 _f 46fi ~

Examples - 2-11

Following the procedure of Example 1, the following imidazo- (4,5-b) pyridine prepared: ■

6-chloro-2-trifluoromethylimidazo (4,5-b) pyridinj white, crystalline pesticide, melting point 304 - 305 ⁰ G.

1Ö9S10 / 218S

- 8 - ■■■ -. ■. '.

6-bromo-2-trifluoromethylimidazo (4,5-b) pyridine; buff-colored solid, melting point 306 - 308 ⁰ C.

6-Bromo-5-methyl-2-trifluoromethylimidazo (4> 5-b) pyridine; pale orange solid, sublimed at 260 ° C-,

6-chloro-5-methyl-2-tr if luormethylimlda zo (4,5-b) pyridine, white solid, melting point 232 ° C.

7-methyl-2-trifluoromethylimidazo (4,5-b) pyriaine, cream £ colored crystals, melting point 226 - 228 ° C.

6-Nitro-2-trifluoromethylimidazo (4,5-b) pyridine, off-white Crystals, melting point 256-258 ° C.

6-bromo-7-methyl-2-trif luormethylimidazo (4,5-b) pyridine, colorless needles, melting point 243-244 ⁰ C.

6-bromo-5,7-dimethyl-2-tr if luormethylimidazo (4,5-b) pyridine, white needles, mp 212- 213 ⁰ C,

7-Methyl-6-nitro-2-trif luormethylimida.zo (4,5-b) pyridine, yellow needles, melting point 179-182 ⁰ C., ·. '

1 (3) - (2,3-dichlorophenyl) -6-nitro-2-trifluoromethylimidazo (4 »5-b) pyridine, cream-colored plates, melting point 171 172 ⁰ C.. ...

Example 12

A solution of 5 * ο parts' 3,4-3) iamino-5-nitropyridine in 38 parts of trifluoroacetic acid was refluxed for 16 hours heated. The mixture was then cooled and the excess acid removed by vacuum distillation. The oily residue was then dissolved in water and partially

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wisely neutralized with alkali. It formed a pale yellow .Niederschlag which is filtered, recrystallized from water and dried at 80 ⁰ C for 6 hours langzur removal of the crystal water to give 3.2 parts of 7-MtrQ-2-trifluoromethylimidazo (4,5-c) pyridine with a melting point of 177-179 ° C.

Analysis found: C 36.22; H 1.30; M $ 24.12 (C ₇ H ₃ P ₃ Xi ₄ O ₃ ) Calcd .: C 35.95; H 1.50; IT $ 24.10

Example 13

A solution of 4.0 parts of 6-bromo-5-methyl-2-trifluoromethylimidazo (4,5-b) pyridine and 2.0 parts of potassium carbonate in 40 parts of dry acetone was stirred with a solution of 1.55 parts of A ' added ethyl chloroformate in 12 parts of dry acetone. The solution was allowed to stand for 2 hours, filtered and the solvent removed in vacuo to give an orange crystalline pest. Recrystallization from petroleum ether (40 60 ⁰ C) to give 3.7 parts of 6-bromo-1 (3) -ethoxycarbonyl-5-methyl-2-trifluoromethylimidazo (4,5-b) pyridin.mit a melting point of -65 - 7O ⁰ C. The yield was 74 $. · '·' ä

Analysis found: C 37.75; H 2.70; Br 22.85; M (C ₁₁ H ₉ BrP ₃ U ₃ O ₂ ): Calculated: C 37.52; H2.58; Br 22.70; N $ 11.93

Examples 14-20

following the procedure of Example 13, the following 1 (3) -carboxy derivatives of imidazo (4 _f 5-b) pyridine were prepared;

6-chloro-1 (3) -ethoxycarbönyl-2-trlfluoromethylimida zo (4,5-b) -pyridine, pale yellow crystals, melting point 123 - 124 ⁰ C.

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6-chloro-1 (3) -phenoxycarbonyl ~ 2-trifluoromethylimidazo (4 »5-b) -pyridiii, pale red crystals, melting point 83-84 ° C.

6-bromo (3) ethoxy carbonyl-2-trifluoromethylimida zo (4,5-b) pyridine, "brown crystals, melting point 163 ° C.

6-Br om-1 (3) -phenoxyearbonyl-2-trif luorme thylimida zo (4,5-b) pyridine, m.p. 87 ⁰ C.

6-chloro-1 (3) -isopropoxycarhonyl-2 * -trifluormethylimidazo- ^ (4J5-b) pyridine, white Peststoff, melting point 72-73 ⁰ C.

5-chloro-6-methyl-1 (3) -isopropoxycarbonyl-2-triffluorine thylimidazo (4,5- "b) pyridine, white Kadeln, melting point 98-99 ⁰ C.

6-chloro-1 (3) - (2 '-chi or ethoxy carbonyl) -2-trifluoromethylimirdazo- (4,5-b) pyridine, colorless threads, melting point 114 116 ⁰ C.

Example 21

14 parts of potassium permanganate were gradually added to a hot solution of 10 parts of 6r-bromo-5-methyl-2-trifluoromethylimidazo (4,5-b) pyridine and 7.5 parts of sodium carbonate in 400 parts of water was refluxed for 2 hours, cooled and filtered The pebble was evaporated to 1/3 of its volume and precipitated 6-bromo-5-oarboxy-2-trifluoromethylimidazo (4,5) pyridine as a fine white plague This was filtered off, dried and recrystallized, giving 7.1 parts of pure 6-bromo-5-carboxy-2-trifluoromethylimidazo (4 »5-b) pyridine, which ^{sublimed at 265 °} C. The yield was 635S.

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Claims (5)

P 16 70 750.9 Fisons Pest Control limited Harston, Cambridgeshire BJU 16 149/65 England Wd / rau Fa tent an e τ> r go 1. Process for the production of optionally substi performed imidazopyridineii of the formula wherein one of the öruppen 2 _f Z, 2 or preferably 2 ¹ "represents a nitrogen atom and the other three S groups for CR ² , CR ⁵ and CR ^ stsnen, and R ¹ for hydrogen, an alkyl, substituted alkyl, aryl -, substituted aryl group, -CYZR ^ or -COR ^, where Y and Z ' ^ Oxygen or sulfur and R ^ is an alkyl, substituted Denote alkyl, aryl or substituted aryl group, and R-, R ^ and R ^ are the same or different are and for hydrogen, alkyl, hydroxy, alkoxy, substituted alkoxy, aryloxy, substituted aryloxy, Nitro, halogen, pseudohalogen, substituted alkyl, carboxy, ester, amide, N-substituted or disubstituted Amide, amino, mono- or disubstituted amino, thiol, alkylthiol groups or their oxygen-containing groups Derivatives, sulfonic acid, their ester, amide or substituted Araid groups or a heterocyclic, are bonded to the imidazopyridine system via a nitrogen atom and X is an iDrifluoromethyl- or 109810/2185 Represents pentafluoroethyl group, characterized in that that he ' - a) an optionally substituted 2,3-diaminopyridine or 3,4-diaminopyridine of the following formula MH ₂ in which Z, Z, Z ^ ₉ Z ^ have the meaning given above, with iDrifluoroacetic acid or pentafluoropropionic acid or a 'functional derivative' of these compounds, b) a salt of an optionally substituted 2,3-diaminopyridine or 3,4-diaminopyridines of the following Pormel in which Z, Z, Z ^, Z and R the above Have meaning with trifluoroacetic acid or a functional derivative of the same in an inorganic halide, c) a salt of a substituted 2,3-diaminopyridine or 3,4-diaminopyridines with trichloroacetic acid, Tribromoacetic acid or triiodoacetic acid or a functional derivative of these compounds in one 109810/2185 ■ converts inorganic halide and the formed 2Dri ~ halomethyl derivative by "treatment with a metal fluoride converted into the corresponding trifluoromethyl derivative. d) compounds prepared according to a) to c) in which R Means hydrogen or an alkali metal, preferably in the presence of a base, reacts with chloroformate, or e) compounds prepared according to a) to d) in which R, R ^ and / or R ^ are CH-, in a manner known per se oxidized, so that COOH groups are formed, f) and optionally in a manner known per se in metal, Amine or quaternary ammonium salts, 2. Imidazopyridines of the general formula Z ² 0-If •. ■ ir 1 Ο "* ι Α in which one of the groups Z, Z, Z ^p and Z ^ is a nitrogen atom and the other three groups CR, CR or CR ⁴ , R for a hydrogen atom, an alkyl, substituted alkyl-aryl or substituted aryl group, -CYZR ⁵ or -COR ⁵ , where Y and Z are an oxygen or sulfur atom and R ^{5 is} an alkyl, substituted alkyl, aryl or substituted aryl group, and R ² , R ⁵ and R ⁴ "can be the same or different and for a hydrogenatora 109810 / 218S. an alkyl, hydroxy, alkoxy, substituted alkoxy, Aryloxy, substituted aryloxy, nitro, halogen, pseudo-halogen, substituted alkyl, carboxy-carboxy ester, Carboxyamide, JS substituted or disubstituted carboxyamide, amino or mono- or disubstituted amino, shiol, alkylthiol group or their oxygen-containing derivatives, sulfonic acid, -ester, -amid and substituted -amidgruppe or a heterocyclic, via a nitrogen atom the ring bound to the imidazopyridine system and X is a trifluoromethyl or pentafluoroethyl group represents, as well as their salts and functional derivatives. 3. imidazopyridine according to claim 8, wherein Ί, represents a nitrogen atom. 4. imidazopyridine of the formula, _R 14 R ¹² --C. C - ¹ R ¹¹ in which R ^{11 stands} for a hydrogen atom or -COOR, where R ¹ ^ means an alkyl or phenyl group, and R, R and R ^ can be the same or different and mean a hydrogen atom, an alkyl group and a halogen atom, as well as their Salsa and functional derivatives. 109810 / 218S B "" QH ". / te ³ - pa 5. The Yerbinätxbgen
pyridla or 109810/7185