CA1237435A - Process for the preparation of substituted benzimidazoles - Google Patents
Process for the preparation of substituted benzimidazolesInfo
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- CA1237435A CA1237435A CA000460703A CA460703A CA1237435A CA 1237435 A CA1237435 A CA 1237435A CA 000460703 A CA000460703 A CA 000460703A CA 460703 A CA460703 A CA 460703A CA 1237435 A CA1237435 A CA 1237435A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
- C07D235/08—Radicals containing only hydrogen and carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
- C07D235/12—Radicals substituted by oxygen atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/18—Benzimidazoles; Hydrogenated benzimidazoles with aryl radicals directly attached in position 2
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Abstract
Case 6-14539/+
Process for the preparation of substituted benzimidazoles Abstract The ruthenium- or rhodium-catalysed reaction of azo-benzenes with tertiary amines containing at least one R-CH2-group, or the ruthenium-catalysed reaction with primary alcohols or their esters with aliphatic carboxylic acids leads to 1-phenyl-2-substituted benzimidazoles.
Process for the preparation of substituted benzimidazoles Abstract The ruthenium- or rhodium-catalysed reaction of azo-benzenes with tertiary amines containing at least one R-CH2-group, or the ruthenium-catalysed reaction with primary alcohols or their esters with aliphatic carboxylic acids leads to 1-phenyl-2-substituted benzimidazoles.
Description
~:37435 6-14539/~
Process for the ereparation of substit d benzimidazoles The present invention relates to a single-stage pro-cess for the preparation of 1,2-substituted benzimidazoles from azobenzenes, a tertiary amine hav;ng at least one R C~2-group or a primary alcohol, or an ester thereof with an al;-phatic carboxylic acid, under the action of a ruthenium and/
or rhodium catalyst.
Sw;ss Patent Specif;cation 478,526 has disclosed that
Process for the ereparation of substit d benzimidazoles The present invention relates to a single-stage pro-cess for the preparation of 1,2-substituted benzimidazoles from azobenzenes, a tertiary amine hav;ng at least one R C~2-group or a primary alcohol, or an ester thereof with an al;-phatic carboxylic acid, under the action of a ruthenium and/
or rhodium catalyst.
Sw;ss Patent Specif;cation 478,526 has disclosed that
2-substituted benzimidazoles, ~hich can aLso be substituted addit;onally in the 1-position, represent outstanding fungi-cides. For preparing this compound, one starting product used is, for example, o-phenylenediamine~ ~hich is reacted ~ith carboxylic ac;d to give the 2-substituted benzimidazolen This process is uneconomical, in particular since some of the starting compounds used are difficult to obtain and are expensive.
The subject of the invention is a process for the preparation of benz;midazoles of the for~ula ~9 ~ C R
R2/ ~7/ \~/ ~ I ) ,, DI/
R ~4~ R
'~
~3'7~3S
;n which R ;s-an al;phat;c or aromat;c hydrocarbon rad;cal or heterocyclic radicalr containing 4 to 8 r;ng atoms and one cr two ;dent;cal or different heteroatoms, wh;ch are unsubstituted or substituted ~y c1-C6-alkyl, C1-C6-alkoxy, C1-C6-alkylthio,cycloalkyl having 3 to 7 ring carbon atoms, phenyl,naphthy~, halogen, hydroxyl, n;tr;lè or amino, and R , R , R , R ~ R , R , R and R independently of one an-other are hydrogen atom, halogen, carboxylate, alkyl, alkoxy, alkylth;o, alkoxyalkyl, cycloalkyl, aryl or aralkyl, or two adjacent groups out of R1, R , R and R or R , R , R and R1 ;n each case represent -CH-CH-CH=CH-, which pro-cess comprises react;ng an azobenzene of the formula Rl\ R9 ~0 ~6 R -~ N=~ R5 (Il) in ~h;ch R1 to R6 and R~ as ~ell as R10 are as defined above, in the presence of a ruthenium or rhodium catalyst or mixtures of such catalysts and at temperatures of at least 120C
~ith a tert;ary amine containing at least one R-CH~ ~roup or, in the presence of a ruthenium catalyst, ~ith a primary aLco-hol or acid ester thereof, of the formula --R ~ CH2 ~ O A (III) ~n which R is as-defined above and A is a hydrogen àtom or à~
a~iphat;c acyt ra~ical, wh;ch ;s un~sùbstitute~ or su~st;~tut~ed -~
by phenyl, halogen, OH, SH or carboxyl. Mixtures of position-;someric benzimidazoles can also be formed in the reactionu An aliphatic hydrocarbon radical R in formula I can be linear or branched alkyl which preferably has 1 to 20, in particular 1 to 12, C atoms and which can be interrupted by hetero-atoms, for example O or S; or it is linear or branched alkenyl having preferably 2 to 20, in particular Z to 12 and especially 2 to 6 C atoms, linear or branched alkynyl having preferably Z to 12, in particular 2 to 6 C atoms, or cytlo-al~kyl having preferably 3 to 10~ in particular 3 to 8 ring carbon atoms. Examples are: methyl, ethyl, propyl, iso-propyl, n-butylO ;sobutyl, tertiary-butyl, penty~O hexylO
, ~ . ~
~37~L3~i heptyl, octyl, nonyl, decyl, dodecyl, hexadecyl, octadecyl, 2-(methoxyethoxy)-ethyl, methylthioethyl, aethenyl, aethynyl, cyclopropyl, cyclobutyL, cyclopentyl, cycLohexyl, cyclo-heptyl and cyclooctyl~
An aromatic hydrocarbon rad;cal R in formula I pre-ferably contains 6 to 16 C atoms and in particular is phenyl or naphthyl.
A heterocycl;c radical R in ~ormula I can be an aro-matic or cycloaliphatic radical. These radicals contain preferably 4 to 8, in particular 4 to 6, r;ng atoms and one or two ident;cal or different hetero-atoms. Examples of hetero-cyclic compounds, from which R is derived, are: pyrrole, pyrroline, pyrrol;d;ne, pyrazole, imidazole~ tetrahydrofuran or dihydrofuran, ~uran, thiophene~ indole~ coumarone, thio-naphthene, oxazole, thiazole, ;sooxazole, ;sothiazole, pyr;dine, pyran, th;opyran, piperid;ne, piperaz;ne, pyrîd-azine, pyrimidine and pyraz;ne.
Examples of suitable substituents for the radical R
are alkyl ha~ing preferably 1 to 6 C atoms, such as methyl~
ethyl, propyl, isopropyl, n-butyl, isobutyl, tert;ary-butyl, pentyl and hexyl, alkoxy and alkylthio having preferably 1 to 6 C atoms, such as methoxy, ethoxy, propoxy~ methylthio and ethylthio, cycloalkyl having preferably 3 to 7 r;ng ~
atoms, such as cyclopropyl, cyclopentyl and cyclohexyl, aryl, such as phenyl or naphthyl, halogen, in particular fLuorine and chlorine, hydroxyl, n;trile and am;no~ ;n part;cular secondary amino having a total of preferably 2 to 1Z C atoms, such as dimethylamino, diethylamino or morpholino.
Of the radicals R1 to R6 as well as R9 and R10, one out of R~ to R3 and R9 and one out of R4 to R6 and R10 ;s in each case preferably a hydrogen atom. ~alogen atoms R1 to R6, R9 and R10 are preferably fluorine, chlorine or bromine. Alkyl R1 to R6 preferably contains 1 to 6, ;n part;cular 1 to 4, C atoms and cycloalkyl preferably contains 5 or 6 r;ng C atoms; aryl has preferably 6 to 12 ~
atoms and ;s in particular phenyl; aralkyl preferably has 7 to 16 C atoms and is in part;cular phenylmethyl or ~-phenyLethyl;
.
~37~35 ~, alkoxy, alkylthio and alkoxyalkyl preferably have 1 to 6 or in the latter, 2 to 6 C atoms and are, for exampleO methoxy, ethoxy, methoxymethyl or methoxyethyl; carboxylate is, for example, a radical of the formula -COOR1, ;n wh;ch R1 is alkyl preferably having 1 to 6 C atoms, cyclohexyl or phenyl.
Tertiary amines containing at least one R-CH2-group are preferably of the formula ~-R
I ~ 8 (IV) ;n which R is as defined above, and R7 and R8 ;ndependently of one another are methyl, ~ -branched alkyl, cycloalkyl, aryl or ~ -branched aralkyl, or R7 and R8 together are trimethylene, tetramethylene or 3-oxapentylene, or R7 and R8 are ident;cal or different R-CH2- groups. Preferably, R7 and R8 are the same as the R-CH2- group. If R7 and/or R8 are different R-CH2- groups~ mixtures of compounds of the formula I with d;fferent radicals R are obtained in the reaction.
C~ -branched alkyl R7 and R8 preferably contains
The subject of the invention is a process for the preparation of benz;midazoles of the for~ula ~9 ~ C R
R2/ ~7/ \~/ ~ I ) ,, DI/
R ~4~ R
'~
~3'7~3S
;n which R ;s-an al;phat;c or aromat;c hydrocarbon rad;cal or heterocyclic radicalr containing 4 to 8 r;ng atoms and one cr two ;dent;cal or different heteroatoms, wh;ch are unsubstituted or substituted ~y c1-C6-alkyl, C1-C6-alkoxy, C1-C6-alkylthio,cycloalkyl having 3 to 7 ring carbon atoms, phenyl,naphthy~, halogen, hydroxyl, n;tr;lè or amino, and R , R , R , R ~ R , R , R and R independently of one an-other are hydrogen atom, halogen, carboxylate, alkyl, alkoxy, alkylth;o, alkoxyalkyl, cycloalkyl, aryl or aralkyl, or two adjacent groups out of R1, R , R and R or R , R , R and R1 ;n each case represent -CH-CH-CH=CH-, which pro-cess comprises react;ng an azobenzene of the formula Rl\ R9 ~0 ~6 R -~ N=~ R5 (Il) in ~h;ch R1 to R6 and R~ as ~ell as R10 are as defined above, in the presence of a ruthenium or rhodium catalyst or mixtures of such catalysts and at temperatures of at least 120C
~ith a tert;ary amine containing at least one R-CH~ ~roup or, in the presence of a ruthenium catalyst, ~ith a primary aLco-hol or acid ester thereof, of the formula --R ~ CH2 ~ O A (III) ~n which R is as-defined above and A is a hydrogen àtom or à~
a~iphat;c acyt ra~ical, wh;ch ;s un~sùbstitute~ or su~st;~tut~ed -~
by phenyl, halogen, OH, SH or carboxyl. Mixtures of position-;someric benzimidazoles can also be formed in the reactionu An aliphatic hydrocarbon radical R in formula I can be linear or branched alkyl which preferably has 1 to 20, in particular 1 to 12, C atoms and which can be interrupted by hetero-atoms, for example O or S; or it is linear or branched alkenyl having preferably 2 to 20, in particular Z to 12 and especially 2 to 6 C atoms, linear or branched alkynyl having preferably Z to 12, in particular 2 to 6 C atoms, or cytlo-al~kyl having preferably 3 to 10~ in particular 3 to 8 ring carbon atoms. Examples are: methyl, ethyl, propyl, iso-propyl, n-butylO ;sobutyl, tertiary-butyl, penty~O hexylO
, ~ . ~
~37~L3~i heptyl, octyl, nonyl, decyl, dodecyl, hexadecyl, octadecyl, 2-(methoxyethoxy)-ethyl, methylthioethyl, aethenyl, aethynyl, cyclopropyl, cyclobutyL, cyclopentyl, cycLohexyl, cyclo-heptyl and cyclooctyl~
An aromatic hydrocarbon rad;cal R in formula I pre-ferably contains 6 to 16 C atoms and in particular is phenyl or naphthyl.
A heterocycl;c radical R in ~ormula I can be an aro-matic or cycloaliphatic radical. These radicals contain preferably 4 to 8, in particular 4 to 6, r;ng atoms and one or two ident;cal or different hetero-atoms. Examples of hetero-cyclic compounds, from which R is derived, are: pyrrole, pyrroline, pyrrol;d;ne, pyrazole, imidazole~ tetrahydrofuran or dihydrofuran, ~uran, thiophene~ indole~ coumarone, thio-naphthene, oxazole, thiazole, ;sooxazole, ;sothiazole, pyr;dine, pyran, th;opyran, piperid;ne, piperaz;ne, pyrîd-azine, pyrimidine and pyraz;ne.
Examples of suitable substituents for the radical R
are alkyl ha~ing preferably 1 to 6 C atoms, such as methyl~
ethyl, propyl, isopropyl, n-butyl, isobutyl, tert;ary-butyl, pentyl and hexyl, alkoxy and alkylthio having preferably 1 to 6 C atoms, such as methoxy, ethoxy, propoxy~ methylthio and ethylthio, cycloalkyl having preferably 3 to 7 r;ng ~
atoms, such as cyclopropyl, cyclopentyl and cyclohexyl, aryl, such as phenyl or naphthyl, halogen, in particular fLuorine and chlorine, hydroxyl, n;trile and am;no~ ;n part;cular secondary amino having a total of preferably 2 to 1Z C atoms, such as dimethylamino, diethylamino or morpholino.
Of the radicals R1 to R6 as well as R9 and R10, one out of R~ to R3 and R9 and one out of R4 to R6 and R10 ;s in each case preferably a hydrogen atom. ~alogen atoms R1 to R6, R9 and R10 are preferably fluorine, chlorine or bromine. Alkyl R1 to R6 preferably contains 1 to 6, ;n part;cular 1 to 4, C atoms and cycloalkyl preferably contains 5 or 6 r;ng C atoms; aryl has preferably 6 to 12 ~
atoms and ;s in particular phenyl; aralkyl preferably has 7 to 16 C atoms and is in part;cular phenylmethyl or ~-phenyLethyl;
.
~37~35 ~, alkoxy, alkylthio and alkoxyalkyl preferably have 1 to 6 or in the latter, 2 to 6 C atoms and are, for exampleO methoxy, ethoxy, methoxymethyl or methoxyethyl; carboxylate is, for example, a radical of the formula -COOR1, ;n wh;ch R1 is alkyl preferably having 1 to 6 C atoms, cyclohexyl or phenyl.
Tertiary amines containing at least one R-CH2-group are preferably of the formula ~-R
I ~ 8 (IV) ;n which R is as defined above, and R7 and R8 ;ndependently of one another are methyl, ~ -branched alkyl, cycloalkyl, aryl or ~ -branched aralkyl, or R7 and R8 together are trimethylene, tetramethylene or 3-oxapentylene, or R7 and R8 are ident;cal or different R-CH2- groups. Preferably, R7 and R8 are the same as the R-CH2- group. If R7 and/or R8 are different R-CH2- groups~ mixtures of compounds of the formula I with d;fferent radicals R are obtained in the reaction.
C~ -branched alkyl R7 and R8 preferably contains
3 to 20, in particular 3 to 12, C atoms. Examples are iso-propyl, ~-methylpropyl and ~ -ethylbutyl. Aryl R7 and R8 preferably conta;ns 6 to 12 C atoms and can, for example, be phenyl or naphthyl. ~ -branched aralkyl R7 and R8 preferably contains 8 to 16 C atoms and can, for example, be ~-phenyl-ethyl, ~ -methyl- ~ -phenylethyl or 1-phenyl~2-ethyl-prop~1-yl.
Cycloalkyl R7 and R8 is especially cyclopentyl and cyclo hexyl. Substituents for R7 and R8 are, for exa~ple~
those described above for R.
The aliphatic acyl radical A in formula III prefer-ably contains 1 to 8, ;n particular 1 - ~, C atoms and can be an aliphatic or cycloaliphatic radical~ Suitable substitu-ents for A are, for example, phenyl~ halogen, in particular fluorine and chlorine, OH~ SH or carboxyl.
Exa~ples of carboxyl;c acids, from which the acyl radical A can be derived, are: formic ac;d~ acetic acid, ~3~ 5 hydroxy acet-ic acid, chloroacetic acid, trichloroacetic acid, propionic acid, butyric acid, phenylacetic acid, cyclopen tanecarboxylic ac;d and cyclohexanecarboxylic acid~
Examples of primary alcohols of the formula III are:
ethanol, n-propanol, n-butanol, ~ -(dimethylamino)-ethanol, ethylene glycol monomethyl ether, diethylene glycol mono-butyl ether, 2-methyl-1-hydroxy-propane, n-hexanol, n-decanol, n-octadecanol, allyl alcohol~ propargyl alcohol, thydroxy-methyl)-cyclopropane, -cyclobutane~ -cyclopentane and -cyclo hexane, (hydroxymethyl)-benzene, (hydroxyme~hyl)-naphthalene, t~ -hydroxyethyl)-benzene, fur~uryl alcohol, thydroxymethyl)-pyrrole or -pyrrol;dine and t ~-hydroxyethyl~-piper;dine.
For reasons of economy, primary alsohols are prefer-red over the esters.
Examples of suitable tertiary amines hav;n~ at least one R-CH2- group are: ethyldimethylamine, diethylmethyl-amine, triethylamine, diphenyl-n-propylamine, phenyldi-n-butylamine, trion-propyalmine, tri-n-butylamine~ tri-t2-methyl)-propylamine, tri-n-pentylamine, tri-n-hexylamine, cyclohexyl-di-n-butylamine, dicyclopentyl-n-propylamine, phenyldibenzylamine, tribenzylamine, tri-~ -phenylethyl~-amine, tri-tcyclohexylmethyl)-amine, dimethyl~tfuranylme~hyl)-amine, ~-ethylmorphoLine, N-(n-propyl)-piperazine and N-tn-butyl)~pyrrolidine.
Examples of suitable azobenzenes are: azobenzene,
Cycloalkyl R7 and R8 is especially cyclopentyl and cyclo hexyl. Substituents for R7 and R8 are, for exa~ple~
those described above for R.
The aliphatic acyl radical A in formula III prefer-ably contains 1 to 8, ;n particular 1 - ~, C atoms and can be an aliphatic or cycloaliphatic radical~ Suitable substitu-ents for A are, for example, phenyl~ halogen, in particular fluorine and chlorine, OH~ SH or carboxyl.
Exa~ples of carboxyl;c acids, from which the acyl radical A can be derived, are: formic ac;d~ acetic acid, ~3~ 5 hydroxy acet-ic acid, chloroacetic acid, trichloroacetic acid, propionic acid, butyric acid, phenylacetic acid, cyclopen tanecarboxylic ac;d and cyclohexanecarboxylic acid~
Examples of primary alcohols of the formula III are:
ethanol, n-propanol, n-butanol, ~ -(dimethylamino)-ethanol, ethylene glycol monomethyl ether, diethylene glycol mono-butyl ether, 2-methyl-1-hydroxy-propane, n-hexanol, n-decanol, n-octadecanol, allyl alcohol~ propargyl alcohol, thydroxy-methyl)-cyclopropane, -cyclobutane~ -cyclopentane and -cyclo hexane, (hydroxymethyl)-benzene, (hydroxyme~hyl)-naphthalene, t~ -hydroxyethyl)-benzene, fur~uryl alcohol, thydroxymethyl)-pyrrole or -pyrrol;dine and t ~-hydroxyethyl~-piper;dine.
For reasons of economy, primary alsohols are prefer-red over the esters.
Examples of suitable tertiary amines hav;n~ at least one R-CH2- group are: ethyldimethylamine, diethylmethyl-amine, triethylamine, diphenyl-n-propylamine, phenyldi-n-butylamine, trion-propyalmine, tri-n-butylamine~ tri-t2-methyl)-propylamine, tri-n-pentylamine, tri-n-hexylamine, cyclohexyl-di-n-butylamine, dicyclopentyl-n-propylamine, phenyldibenzylamine, tribenzylamine, tri-~ -phenylethyl~-amine, tri-tcyclohexylmethyl)-amine, dimethyl~tfuranylme~hyl)-amine, ~-ethylmorphoLine, N-(n-propyl)-piperazine and N-tn-butyl)~pyrrolidine.
Examples of suitable azobenzenes are: azobenzene,
4-methylazobenzene, 4,4'-dimethylazobenzene, 4,3' dimethyl-azobenzene, 4-fluoroazobenzene, 4-fluoro-4'-chloroazobenzene, 3-bromoazobenzene, 4,4'- or 3,4'-dichloroazobenzene, 3,5-di-chloroazobenzene, 3,5-dimethylazobenzene, 3,3'-, 4,4~ and 3,~-diethylazobenzene, 4-methoxyazobenzene, 4-(methoxymethyl)-azobenzene, 4-phenylazobenzene, 3-tmethoxycarbonyl)-azo-benzene, 3-benzylazobenzene, naphthaleneazobenzene, 4,4 difluoroazobenzene, 3,3'-, 5,5' tetramethylazobenzene, 4-chloro 4'-methylazobenzene, 4-~luoro-4'-methylazobenzene, 4-methyl-4'-tethoxycarbonyl)-azoben7ene, 3,5 dichloro-4~-methylazobenzene, 3~3'-dimethylazobenzene and 4-methyl 4-methoxyazobenzene~
~37a~3~
Under the applicable reaction conditions, the azo-ben~ene can also be replaced by corr,esponding N'-phenylated o-phenylenediamines.
The catalysts are preferably used in quantities of .001 to 20 mol %, ;n particular 0~01 to 10 mol ~ and especi-ally 0.0~ to 5 mol ~. These can be heterogeneous catalysts, for example ruthenium on a suitable support material such as carbon, or preferably homogeneous catalysts which are soluble in the reaction mixture. Examples of homogeneous catalysts are compounds of ruthenium or rhodium, in particular their salts of inorganic or organ;c ac;ds, and complex compounds thereof. The complexes can be mononucLear or poLynuclear and they can contain polyfunct;onal, preferably monofunct;onal l;gands. Such ligands are descr;bed, for example~ in Ad-vanced Inorganic Chemistry, 4th Edition, published by Wiley New York (1980), pages 107 to 194. The compounds or com-plexes can be in any oxidation stages of the ruthen;um or rhodium; the preferred oxidation stages are 0~ 1, 2, 3 and 4.
Suitable salts of ruthenium or rhodium are der;ved, for example~ from the following acids: formic acid~ acetic acid, benzoic acid, toluenesulfon;c acid, phosphoric acid, sulfuric acid, perchlor;c acid and hydrofluoric, hydrobromic, hydriodic and in particular hydrochloric acid. The salts can also be used in their hydrated form. Ruthenium trirhloride tr;hydrate and rhodium tr;chloride-trihydrate are particu larly preferred~
Amongst the complexes, those with carbonyl ligands are particularly preferred. Dodecacarbonyl-triruthenium is one example. In a preferred embodiment of the proGess accor-ding to the invention, the carbonyl complexes are formed be-fore or during the reaction from, for example, the abovemen-tioned salts, by carry;ng out the reaction under a pure car-bon monoxide atmosphere or under mixtures of carbon monoxide with an inert blanket gas, for example9 ni~rogen or a rare gas, such as helium or argon.
Further l;gands are compounds with donor atoms, for _ 7 _ ~ ~3~4~
example P~ N, As, Sb, B;, O, S and Se, and anions of or-ganic or ;norganic ac;ds~ Examples are the arsines, sti-b;nes, bismuthines and in particular the phosphines. Further examples of l;gands are fluor;de, brom;de, chloride, iodide~
hydride, the trichloro-tintII) anion, dimethyl sulfoxide, nitrosyl, the acetate anion and the acetonyl acetate anion.
Ligands with tr;valent elements of the fifth ma;n group of the periodic table are ;n part;cular am;nes, phosphines~
ars;nes, st;b;nes and b;smuth;nes, espec;ally those with aryl radicals, for example phenyl which can be substituted by halogen ~F, Cl), C1-C4-alkyl or C1-C4-alkoxy. Further radicals are alkyl having preferably 1 to 12 C atoms, yclo-alkyl, for example cyclohexyl, and aralkyl, for example benzyl~ The phosphines are the preferred ligands from this group. Examples are:
Triphenylphosphine~ tri-~o-toluyl)-phosphine, tri-~p-toluyl)-phosphine, tri-(p-fluorophenyl)-phosphine, tri-tp-methoxyphenyl)-phosphine, tertiary~butyldiphenylphosphine, ~ricyclohexylphosphine, tetraphenyldiphosphine~ triphenyl-amine and tr;phenylstib;ne. Phosphites are also suitableO
in particular those ~ith aryl radicals such as phenyl. Tri-phenyl phosphite is an example. The complexes can conta;n identical or different ligands. Preferably, the compl~xes conta;n phosph;ne ligands and CO l;gands.
The complexes can be added as isolated compounds at the beginn;ng of the reaction. It has proved to be expe-dient to prepare the complexes before the start of the re-action from ruthenium or rhodium compounds ~for example their salts~ by adding the ligand-forming compounds, if appropriate in a CO atmosphere, and then to proceed with the process accord;ng to the invention by adding the reactants.
The ligand-form;ng compounds can be added in equi-molar amounts or in excess~ The molar ratio of the ruthenium or rhodium compounds and the ligands is preferably 10:1~ in particular 6 to 2~
In a preferred embodiment of the process, ruthenium or rhodium compounds~ in particular ~heir halides, are em-~2379L35 -- 8 --ployed as a reactant, if ~ertiary amines having at least one RCH2- group are used, and advantageously the reaction is additionally carried out under a C0 atmosphere.
In a further preferred embodiment of the process, ruthenium complexes, preferably those with phosphine ligands, are employed as reactants, if primary alcohols, or esters thereof, of the formula III are used, the reaction espe-cially being carr;ed out addit;onally under a C0 atmosphere.
It has also proved to be advantageous~ if reactants of the formula III are used, to add a basic compound in addit;on, in order to obtain higher yields. The quantity is pre~erably 0.1 mol %, pre~erably 0.1 to 6û and in particular 0.1 - 20 mol ~ relative to the azobenzene of the formula IIu Examples of suitable basic compounds are primary, secondary and espec;ally tert;ary am;nes, includ;ng those of the formula IV. Amines of the formula IV are preferably added in catalytic quantities, for example in quantities of 0.1 to 2~ mol X, relative to the azobenzene of the formula II. Examples of further amines are methylamine, dimethyl-amine, tr;methylamine~ cyclohexylamine, cyclohPxyldimethyl-amine, morphol;ne, N-methylmorpholine, piperidine~ N-methyl-p;per;dine, pyrrolidine, N-methylpyrroLidine and benzyldi-methylamine.
Further suitable basic compounds are metal salts of carboxylic acids, in part;cular alkal;ne earth metal s~lts~
for example calcium and strontium salts, and especially the alkali metal salts of carboxylic acids. Potassium and in particular sodium and lithium are the preferred alkali metals.
Examples are:
Sod;um bicarbonate~ lithium acetate, lithium pro-pionate, lithium formate, lithium benzoate, sodium acetate and sodium benzoate~
The reactants can be employed in equimolar quanti-ties, or an excess of tertiary amines having at least one RCH2- ~roup or of a primary alcohol or its carboxylic acid ester can be used~ The excess selected can be such that these reactants serve at the same time as the sol~ent~ Of ~23~3~
_ 9 _ course, mixtures of the abovementioned reactants can also be employed.
If equ;molar quantities or a small excess are em-ployed, an inert soLvent ;s advantageously also used. Polar aprotic solvents are part;cularly suitable. N-alkylated ac;d amides are preferred. In view of the reaction tempera-tures, higher-boiling solvents are also preferred, in order to enable the process to be carried out under normal pressure.
Examples of solvents are: hydrocarbons, such as benzene, toluene, chlorobenzene, dichLorobenzene, benzo-nitrile and tetral;n, ac;d esters, such as ethylene carbonate, tr;ethyl phosphate and ethyl benzoate, sulfones, such as tetramethylenesulfone, sulfoxides, such as dimethyl sulfoxide, tertiary amines, such as diphenylmethylam;ne, cyclohexyldi-methylamine and N-methylpiper;d;ne, ethers~ such as d;oxane, d;ethylene glycol dimethyl or diethyl ether and triethylene glycol dimethyl ether, and linear or cycl;c N-alkylated acid am;des, such as tetramethylurea, dimethylformamide, dimethyl-acetamide, d;ethylacetamide, N-methylpyrrolidoneO N--formyl-morpholine, N-~ormylpiperidine and hexamethyl-phosphoric acid triamide. The preferred solvents are diethylformamide, dimethylacetamide~-N-formylmorpholine and in particular te~ra-methylurea and 1,3-dimethyl-2-imidazolidone.
The process is carried out in apparatus conventional for this purpose, by mixing the reactants, the catalys~ and~
if appropriate, a solvent and then heating the react;on mix-ture to the desired reaction temperature. This is prefer-ably 120 to 230C, in particular 15~ to 230C and especially 150 to 200C. The process can be carried out under normal pressure or elevated pressure.
The benzimidazoles of the formula I are isolated in the convent;onal manner, for example by crystallisation or distillation a~ter removal of the solvent.
The process accord;ng to the invention gives, by means of a novel reaction, 1,2-substituted benzimidazoles in good yields and good purity from readily accessible and in-expensive startin~ materials. The 1,2~substituted ben~imi-~3~35 dazoles can be used especially as leaf fung;cides.
The examples wh;ch follow explain the invention in more detail. The yields refer to the azobenzene employed.
Example 1:
12.5 ml of tetramethylurea are init;ally introduced into a reflux apparatus equipped with a thermometer, gas in-let tube and bubble counter. Carbon monoxide under normal pressure is passed through with stirring, and ~.55 9 (25 mmol) of azobenzene, 2.98 ml (1~.5 mmol) of tri-n butylamine and 0.0654 9 ~0.25 mmol) of ruthen;um trichlor;de-tr;hydrate are added. The reaction mixture is heated for 17 hours under reflux (175-177), carbon monoxide being continuously passed through. After removal of the solvent, the mixture is then dist;lLed off in vacuo. This gives 1.64 9 (6.95 mmol) of 1-phenyl~2-n-propylbenzimidazole as a yellow oil, corres-ponding to a yield of 56X of theory, relative to tri-n-butyl-amine, bo;ling point 145-~48/0.2 mm Hg.
Example 2:
The procedure described in Example 1 is repeated, except that 50 ml of tetramethylurea~ 18.2 9 (100 mmol) of azobenzene, 23.86 ml (100 mmol) of tri-n-butylam;ne and 0~2615 9 (1 mmol) of ruthenium trichloride-trihydrate are used. After 8 hours' reflux (175-178), the mixture is worked up as in Example 1. This gives 14.1 g tS9.7 mmol) of 1-phenyl-2-n-propylbenzimidazole as a yellow oilD correspon-ding to a y;eld of 60% of theory.
Examples 3-19:
rhe procedure described in Example 1 is repeated, except that 12.5 ml of solvent, 4~55 g ~25 mmol) of azo-ben2ene, 5.96 ml ~25 mmol) of tri-n-butylamine and 0.0654 9 ~0.25 mmol) of ruthenium trichloride-~rihydra~e are used.
After a reaction period of 6 hours at 170, the yield is determined by gas chromatography. The results are listed in the table.
~;~3~7~3~i Example No. Solvent __ _ Yield 3 Tetramethylurea 39 4 Diethylformamide28 N-Formylmorphol;ne25 6 N-Formylpiperidine14 7 Dimethylacetamide46 8 DiethyLacetamide12 9 N-Methylpyrroli done 19 Hexamethylphosphoric acid triamide 8 11 Sulfolan 22 12 Dimethyl sulfoxide 9 1~ Ethylene carbonate 9 14 Triethyl phosphate 10 ~enzonitrile 7 16 o-Dichlorobenzene26 17 Diethylene glycol ethyl ether 12 18 Tetralin 14 19 Tri-n-butylamine 14 .
* Reflux at 165-167 Examples 20 23:
The procedure described in Example 3 is re-peated, but under reflux conditions and with the volumes of tetramethylurea ~TMU) and reaction times given in the table. The yield is determined by gas chromatography~
~%~
21 12.5 10 67 22 6~25 10 ~ 34 Examples 24 -_26:
The procedure described in Example 3 is repeatedD
except that N-formylmorphol;ne is used as the solvent, and at the temperatures given in the table. The yield is deter-mined by gas chromatography.
3L~37435 Example No. _Temperature tC) Yield (%) 2$ 190 52 . .
Examples 27-28:
The procedure described in Example 21 is repeated, except that the quantities of tri-n-butylam;ne given in the table are employed. The yield is determined by gas chroma-tography.
Example No~ Tri-n-butylamine tmmol) Yield tX) 27 31.25 45 28 3?~5_ _ 45 Examples 29-36:
The procedure described in Example 21 is repeated, except that ;n each case 1 mol X of ruthenium trelative to azobenzene) is used as the catalyst in the form of the com-pounds indicated in the table. To illustrate the effect of carbon monoxide, the experiments are also carried out with argon being passed through instead of carbon monoxide~ The yield is de~ermined by gas chromatography.
Example No. Catalyst Yield ~X) - _ _ _ under C0 Unde_r Ar 29 RuCl3 3 HzO ~7 RuCl~3H20 9 31 RU3tCO)12 32 RU3(CO)12 33 Ru(oAc)2(pph3)2 24 34 RU(oAc)2tpph3)2 CRu2SOAc)4~Cl 58 36 CRu2tOAc)4]Cl 10 Examples 37-44:
The procedure described in Example 21 is repeated~
except that in each case 1 mol X (relati~e to a~obenzene) of the ruthenium compounds and complex formers indicated in the table are used as the catalyst. The yield is determined by gas chromatography.
~3~435i Exarnple No. CataLyst Yield (S~) 37 RuCl2 tDMSO)4 73 38 Ru(acac)3 17 39 RuCl33HzO ~ 2 AsPh3 67 RuCl33H20 + 2 SbPh3 49 41 RuCl33H20 + 2 Pph3 47 42 RuCl33H20 ~ 2 P(Oph)3 66 43 RuCl33H20 ~ Ph2PCH2CH2Pph2 8 44 RuCl33H20 + 2 PMe3 5 Example 45:
The procedure described in Example 21 is repeated, ex-cept that 0.00654 9 S0.025 mmol) of ruthenium trichloride-trihydrate is used. After a reaction time of 24 hours, 0.65 9 t2.75 mmol) of 1-phenyl-2-n-propylbenz;midazole, correspon-ding to a yield of 11% of theory, ;s obtained.
Example 46:
The procedure described in Example 21 is repeated, except that 18.2 9 t100 mmol) of azobenzene, 18~95 ml t100 mmol) of tri-n-propylamine, 0.2615 9 (1 mmol) of ruthenium trichloride-trihydrate and 50 ml of tetramethylurea are used.
After 16 hours under reflux conditions t162-164), the solvent is removed and the product is distilled in vacuo. Th;s gives 6.5 9 t29.3 mmol) of 1-phenyl-2-ethylbenzimidazole as a yellow oil of boiling point 148-15ZC/0.35 mm llg, corres-ponding to a yield of 29% of theory.
The procedure described in Example 46 is repeated, except that 17.33 ml t100 mmol) of n-hexyldimethylamine are used in place of tri-n-propylamine. After 23 hours under reflux conditions, the solvent is removed and the product ;s distilled in vacuo Th;s gives 5.34 9 t2û.~ mmol~ of 1-phenyl-2-n-pentylbenzimidazole as a yello~ oil of boiling point 160-161C~0.6 mm Hg, corresponding to a yield of 20%
of theory~
The procedure described in Example ~6 is repeated, 37~3S
except that 21.0 9 (100 mmol3 of 4,4'-dimethylazobenzene and 18.56 9 (100 mmol) of tr;-n-butylamine are used in place of azobenzene and tri-n-propylamine. After 23 hours under reflux conditions ~178), the solvent is removed and the product is distilled ;n vacuo. It ;s then subjected to chromato-graphy on silica gel in ether and the ether is removed. The product is recrystallised from 100 ml of pentane. This gives 12.5 g (47.3 mmol) of 1-(4'-methylphenyl)-2-n-propyl-6-methylbenzimidazole as white crystals of melting point 88.8C, corresponding to a yield of 47% of theory.
Example 49.
The procedure of Example 47 is repeated, except that 26.95 g (100 mmoL) of tri-n-hexylamine are used in place of n-hexyldimethylamine~ After 8 hours under reflux conditions (1~0C) and working up in accordance ~ith Example 47, this gives 4.45 g (16.9 mmol3 of 1-phenyl-2-n-pentylbenzimidazole as a yellow oil of boiling point 160-161C/O.o mm Hg, cor-responding to a yield of 17X of theory.
Example 50:
The procedure described in Example 48 is repeated, except that 25.1 9 (100 mmol) of 4,4'-dichloroazobenzene are used in place of dimethylazobenzene. After 23 hours under reflux conditions ~180) and distillation as ;n Example 48, the product is recrystallised from 30 ml of n-hexane.
This gives 2.98 g (9.8 mmol~ of 1-(4'-chlorophenyl~-2-n-propyl-6-chlorobenzimidazole as lig~t brown crystals of melting point 100.2C~ corresponding to a yield of 10~ of theory.
Example 51:
The procedure described in Example 48 is repeated, except that 21~8 9 (100 mmol) of 4,4'-difluoroazobenzene are used in place of dimethylazobenzene. After 23 hours under reflux conditions and distillation in accordance ~ith Ex-ample 48, the product is recrystallised from 130 ml oF ~-pentane. This gives 9.17 g ~33.7 mmol) of 1-(4'-fluorophenyl)-2~n-propyl-6~fluorobenzimidazole as white crystals of melt-ing point 75.3C, corresponding to a yield of 34~ of theory.
~37~
Example 52 The procedure described in Example 1 is repeated, except that 11.9 9 (S0 mmol) of 3~3',5~5'-tetramethylazo-benzene, 9.18 g t50 mmol) of tri~n-butylamine, 0.131 9 (D~S
mmol) of ruthenium trichloride-trihydrate and 25 ml of tetra-~ethylurea are used. After 9 hours under reflux conditions (80-181), the solvent is removed and the product is dis tilled in vacuo. Two recrystallisations from 50 ml of n-hexane each time give 3.04 9 (10.~ mmol) of 1-(3',5'-dimethyl)-2-n-propyl-4,6-dimethylbenzimidazole as white crys~als of melting point 118.3C, corresponding to a yield of 21X of theory.
Example 53:
The procedure described in Example 52 is repeated~
except that 11.53 g ~50 mmol) of 4-chloro-4'-methylazoben-zene are used ;n place of tetramethyla20benzene. After 12 hours under reflux conditions tl80C) and d;stillation as in Example 52~ the product is recrystallised tw;ce from 50 ml of n-pentane. This gives 5.0 9 (17.6 mmol) of a mixture of isomers, which consists of 94% of 1-(4'-methylphenyl)-2-n-propyl-6-chlorobenzimidazole and 6% of 1-t4'-chlorophenyl)-2-n-propyl-6-methylbenzimidazole~ as yellow crystals~ corres-ponding to a total yield of 35X of theory. After a further recrystallisation from S0 ml of n-hexane, the pure main iso-mer of the product is obtained as white crystals of melting point 92.9C in 3 yield of 20% of theory.
Example 54:
The procedure described in Example 52 is repeated, except that 10.7 9 ~50 mmol) of 4-fluoro-4'-methylazobenzene are used in place of tetramethylazobenzene~ After 23 hours under reflux conditions (17~-18~C) and distillation in accordance with Example 52, the product is recrys~allised twice from 50 ml of n-pentane. This gives 4.3 9 ~16.1 mmol) of a mixture of isomers, which consists of 71% of 1-~4'-methylphenyl)-2-n-propyl-6-fluorobenzimidazole and 29% of 1-(4'-fluoromethyl)-2-n-propyl-6-methylbenzimidazole, as ~hite crystals, corresponding to a total yield of 32% of - 16 ~237~35 theory~ After a further recrystall;sation from 50 ml of n~hexane, the pure main isomer of the product is obtained as white crystals of melt;ng point 86.7 ;n a yield of 15~ of theory.
ExampLe 55:
The procedure described in Example 52 ;s repeated, except that 13.3 9 t50 mmol) of 4-methyl-4'-ethoxycarbonyl-azobenzene are used in place of tetramethylazobenzene. After 23 hours under reflux conditions (180C) and dist;llation in accordance w;th Example 52~ the product is subjected to chromatography on s;l;ca gel in ether. After removal of the ether, the product ;s recrystallised from 55 ml o~ n-hexane.
This gives 2.27 9 t7.05 mmol) of 1-(4'-methylphenyl)-2-n-propyl-6-ethoxycarbonylbenzimidazole as white crystals of melting point ~0.2C, corresponding to a yield o~ 14% of theory.
Example 56:
The procedure described in Example 1 is repeated, except that ~.5 9 ~36 mmol) of 3,5-dichloro-4'-methylazo-benzene, 6.61 g (36 mmol) of tri-n-butylam;ne, ~.094 9 (0.36 mmol) of ruthenium trichloride-trihydrate and 18 ml of tetra-methylurea are used. After 23 hours under reflux conditions (177-180C), the solvent is removed and the product is d;st;lled ;n vacuo and then recrystallised once from 50 ml of cyclohexane and once from a mixture of 50 ml of hexane and 25 ml of cyclohexane. This gives 2.3 g t7.2 mmol) of 1-t3',5'-dichlorophenyl)-2-n-propyl-6-methylbenzim;dazole as white crystals of melting point 16~.6C~ corresponding to a yield of 20% of theory.
Example 57:
The procedure described in Example 52 is repeated, except that 1~.9 g (50 mmol) of 404'-difluoroazobenzene and 8.15 9 t50 mmol) of dimethyl-t3-phenyl-n-propyl)-amine are used in place of tetramethylazobenzene and tri-n-butylam;ne.
After 22 hours under reflux conditions (18~~) and distil lation in accordance with Example 52, the product is recrys~
tallised twice from 75 ml of n-hexane~ This gives 2.6 9 ~23~3S
(7.8 mmol) of 1-~4'-fluorophenyl)-2-(2-phenylethyL)-6-fluoro-benzimidazole as white crystals of melting point 111.7C, corresponding to a yield of 16~ of theory.
Example 58:
The procedure described in Example 57 is repeated, except that 7.05 9 (50 mmol~ of dimethyl-~cyclohexylmethyl)-amine are used in place of dimethyl-(3-phenyl-n-propyl)-amine. After 22 hours under reflux conditions (175 180C) and distillation in accordance with Example 52, the product is recrystallised twice from 50 ml of pentane. This gives 1.85 9 (5~9 mmol) of 1-(4'-fluorophenyl)-2-cyclohexyl-6-fluoro-benzimidazole as yellow crystals of melting point 115.1C, corresponding to a yield of 12X of theory.
ExampLe 59:
The procedure described in Example 57 is repeated, except that 6.95 9 (50 mmol) of dimethyl-(3-cyclohexenyl-methyl)-amine are used in place of dimethyl-(3-phenyl-n-propyl)-amine. After 23 hours under reflux conditions (17~-180C) and d;stillation in accordance with Example 52, the product is recrystallised once from 100 ml of n-pentane and once from 80 ml of n-pentane. This gives 1.04 g ~3.35 mmol3 of 1-(4'-fluorophenyl)-2-t3-cyclohexenyl)-6-fluorobenzimid~
azole as white crystals of melting point 100.1C, correspond-ing to a yield of 7% of theory.
The procedure described in Example 46 is repeated, except that 21.0 9 ~1~0 mmol) of 4,4'-dimethylazobenzene are used in place of azobenzene. After 72 hours under reflux conditions t161-164C), the product is distilled in accor-dance with Example 46 and then recrystallised from ~0 ml of n-hexane. This gives 10.0 g (40 mmol) of 1-(4'-methylphenyl~-2-ethyl-6-methylbenzimidazole as white crystals of melting point 84.0C~ corresponding to a yield of 40% of theory.
~e~
The procedure described in Example 4O is repeated, except that 19.6 9 (1~0 mmol) of 4-methylazobenzene and 18.56 ~ (100 mmol) of tri-n-butyla~ine are used in place of ~ 237~L35i azobenzene and tri-n-propylamine. After 22 hours under reflux condit;ons (178-180C), 100 ml of 2N hydrochloric ac;d are added to the reaction mixture which is then extrac-ted twice with 100 ml of ether. The aqueous phase is ren-dered alkaline w;th 110 ml of 2N sodium hydroxide solution and extracted three times with 100 ml of ether. After dry-ing of the extract with magnesium sulfate and removal of the ether, the crude product is subjected to chromatography on silica gel in ether. After removal of the ether and distil-lation in ~acuo, the product is recrystallised from 100 ml of n-pentane. This gives 11.1 9 ~44.4 mmol) of a mixture of isomers, ~h;ch cons;sts of 71~ of 1-~4' methylphenyl~-2-n-propylbenzimida~ole and 29% of 1-phenyl-2-n-propyl-6-methyl-benzimidazole, as white crystals, corresponding to a total yield of 44% of theory.
Example 62:
The procedure descr;bed ;n Example 46 is repeated, except that 21.~5 9 ~10n mmol~ of 4-chloroazobenzene are used ;n place of azobenzene. After 8 ho~rs under reflux condit;ons (178C) and workîng-up in accordance ~;th Ex-ample 61, the product is dist;lled once more. This gives 10.~ 9 (38.4 mmol~ of a mixture of isomers, which consists of equal parts of 1-t4'-chLorophenyl)-Z-n-propylbenzimidazole and 1-phenyl-2-n-propyl-6-chlorobenziMidazole, as a yellow oil~ corresponding to a total yield of 38% of theory.
Example 63~
The procedure described in Example 52 is repeatedO
except that 10u5 9 t50 mmol) of 3,3'-d;methylazobenzene are used in place of tetramethylazobenzene~ After 22 hours under reflux cond;tions (179-180C), the product is distilled in accordance with Example 52 and recrystall;sed twice from 50 ml of n-hexane. This gives 3.2 9 (12u1 mmol) of a mix;
ture of ;somer~, which consists of 71% o~ 3'-me~hylphenyl~-2-n-propyl-7-methylbenzimidazole and 29~ of 1-(3'-methyl-phenyl)-2-n-propyl-5 methylbenzimidazole~ as white crystals~
corresponding to a total y;eld of 24~ of theory.
~L~3~3 Example 64:
The procedure described in ExampLe 52 is repeated, excep~ that 11.~ g ~50 mmol) of 4-methyl-4'-methoxya20benzene are used ;n place of tetramethylazobenzenel After 23 hours under reflux conditions ~180C) and d;stillat;on in accor-dance with Example 52, the product is subjected to chroma-tography on s;l;ca gel in ether. After removal of the ether, the product is recrystallised from 50 ml of n-pentane. This g;ves 1.92 9 ~6.9 mmol) of a mix~ure of isomers, which con-s;sts of 80~ of 1-~4'-methoxyphenyl)-2-n-propyl-6-methyl-benzimidazole and 20% of 1-~4'-methylphenyl)-2-n-propyl-6-methoxy-benzimidazoler as white crystals, corresponding to a totaL yield of 14% of theory.
Example 65:
The procedure descr;bed in Example 21 is repeated~
except that 1 g of 5% of ruthenium on active charcoal is used as the catalyst in place of ruthenium trichloride-tri-hydrate. After 8 hours under reflux conditions, this gives 0.3 9 (1.3 mmol) of 1-phenyl-2-n-propylbenzimidazole, cor-responding to a yield o~ 5X of theory.
Example 66:
The procedure described in Example 21 is repeated~
except that 4.60 9 ~25 mmol) of N-phenyl-o-phenylenediamine are used in place of azobenzene. After 4 hours under reflux conditions and after distillat;on, this gives 3~12 9 ~13.2 mmol) of 1~phenyl-2-propylbenzimidazole as a yellow oil, corresponding to a yield of 53% of theoryu Example 67:
The procedure described in Example 21 is repeated, except that 0.0659 9 ~0.25 mmol) of rhodium trichloride tri-hydrate are used in place of ruthenium trichloride-trihydrate~
After 8 hours under reflux conditions, this gives 1.65 9 ~7.0 mmol) of 1-phenyl-2-n propylbenzimida~ole, corresponding to a yield of 28%.
Examples 68-71:
14.8 ml of n-butanol are initially introduced into a pressure tube, and carbon monoxide is passed through with :L~37~L3S
st;rring. 4.55 g (25 mmol) of azobenzene, 2.05 g (25 mmol) of sodium acetate, 0.0654 g (0.25 mmol) of ruthenium tri-chloride-trihydrate and 0.262 9 (1 mmol) of tr;phenylphos-phine are added, and the tube is sealed under carbon monoxide.
After stirring for 8 hours at the temperatures indicated in the table, the 1-phenyl-2-n-propylbenzimidazole formed is determined by gas chromatography.
Example ~o~ Temperature ~C)Yield (%) Examples 72-76:
The procedure described in Example 6~ is repeated~
except that the bases indicated in the table are used~ The yields are determined by gas chromatographyO
Example NQ. Base Yield (%) 72 Sodium benzoate 31 73 Lithium acetate-dihydrate*55 74 Tri-n-butylam;ne 58 N-benzyldimethylamine 69 76 Sodium bicarbonate 20 * 16 mmol Examples 77-80:
The procedure described in Example 73 is repeated~
except that 4.57 ml (5~ mmol) of n-butanol and 12.5 ml of the solvents ind;cated in the table are usedO The yields are determined by gas chromatography.
Example No. Solvent _ Yield (%) 77 N~N dimethylformamide 6 78 N,N-dimethylacetamide 53 79 ~-methylpyrrolidone 64 Tetramethylurea 65 1;~37~L3~;
Examples 81-85:
The procedure described in Example 80 is repeated, except that the quant;ties of tr;phenylphosph;ne ;nd;cated in the table are usedn The y;elds are determ;ned by gas chromatography.
Example No. mmol of tr;phenylphosph;ne_ Yield (X) 82 0.75 63 84 1.25 69 1.5 3~
.. ~ .
Examples 86-90:
The procedure descr;bed ;n Example 83 is repeated~
except that the quantit;es of l;thium acetate-dihydrate in-dicated in the table are used. The yields are determ;ned by gas chromatography.
Example No. mmol of lithium aceta~e-d;hydrate Y;eld ~%) 86 0 ~6 87 1.6 64 8~ 4 65 .
Examples 91-94.
The procedure described in Example 87 ;s repeated, except that the quantities of n-butanol indicated in the table are used. The y;elds are determined by gas chromato-graphy.
Example ND. mmol of n-butanol Yield (X?
~2 5~ 72 93 75 6~
_ 94 125 69 Examples 95-97:
The procedure descr;bed in xarnple 90 ;s repeated, except that 6D86 ml ~75 mmol) of n-butanol and the quantities of ruthenium ~r;chloride-trihydrate and triphenylphosph;ne ~;~3~
(Pph3) indicated in the table are used. The yields are determined by gas chromatography.
Example No. mmol of RuCl3 3H20 mmol of Pph3 Y;eld ~%
00125 0~5 62 96 O.û5 0.2 26 97 _ __ 0 025 _ 0.1 19 Examples 98 107:
The procedure described in Example 95 is repeated~
except that 0.165 9 ~1.6 mmol) of lithium acetate dihydrate is used and the ligands indicated in the table are used in place of triphenylphosphine. The yields are determined by gas chromatography~
Example No. Ligands ~0~5 mmol)Yield ~X) 98 Tris-~o-tolyl)-phosph;ne 36 99 Tr;s-tp-tolyl)-phosphine 58 100 Tris-~p-fluorophenyl)-phosphine 53 101 Tris-(p-methoxyphenylj-phosphine 55 102 Triphenyl phosph;te 6 103 Tris-n~butylphosphine 2 104 t-Butyldiphenylphosphine 41 105 Tricyclohexylphosphine 11 106 Bis-~diphenyLphosphine~-methane*11 107 Bis-~diphenylphosphine)-butane* 8 * 0.25 mmol Examples 108-112:
The procedure described in Example 93 is repeated, except that the quantities of sodium acetate indicated in the table are used in pLace of lith;um acetate-dihydrate.
The yields are determined by gas chromatography.
Example No. mmol of sodium acetate Yield ~%) 108 û.25 21 111 1~25 53 112 __ 2.5 _ _ _ 48__ _ Example 113 25 ml Qf tetramethylurea are initially introduced ~37~3~
into a pressure tube, and carbon monoxide ;s passed through.
9.1 9 (50 mmol) of azobenzene, 10.8 ml t100 mmol) of n-pentyl alcohol, 3.3 9 ~32 mmol) of lith;um acetate-dihydrate, 0.1308 g (0.5 mmol) of ruthenium trichloride-~rihydrate and 0.524 9 (2 mmol) of triphenylphosphine are added. The tube is sealed under carbon monoxide and st;rred for 8 hours at 180C. After removal of the solvent, the product is dis-tilled in vacuo, subjected to chromatography on silica gel in dichloromethane and then recrystallised from 50 ml of pentane. This gives 3.7 9 (14.8 mmol) of 1-phenyl-2-n-butyl-benzimidazole as white crystals of melting point 59.6C, corresp`onding to a yield of 30% of theory.
Example 114:
25 ml of tetramethylurea are initially ;ntroduced into a pressure tube, and carbon monox;de ;s passed through.
9.1 9 ~S0 mmol) of azobenzene, 21.17 ml (150 mmol3 of n-hep-tanol~ 0.123 g (1.5 mmol) of sodium acetate, 0.1308 9 (0.5 mmol) of ruthen;um trichlor;de-trihydrate and 0.524 g (~ mmol) of triphenylphosphine are added, and the tube is sealed under carbon monoxideO After 8 hours at 180C, the solvent is removed and the product is dist;lled in vacuo. It is then subjected to chromatography on silica gel in eth~r and is distilled once more. This gives 5.54 9 (19.9 mmol) of 1-phenyl-2-n-hexylbenzimidazole as a light yellow liqu;d of boiling point 165-168C/0.25 mm Hg, corresponding to a yield of 40X of theory.
Example 115:
The procedure described in Example 113 is repeated, except that 7.91 9 (100 mmol) of hydroxymethylcyclopropane are used in place of n-pentyl alcohol. After 8 hours at 180C, the product is distilled, subjected to chromato-graphy on silica gel in dichloromethane and dist;lled once more in vacuo. This gives 5~2 9 ~Z2~2 mmol) of 1-phenyl-2-cyclopropanylbenzimidazole as a yellow oil of boiling point 146-148C/0.1 mm Hg, corresponding to a yield of 45% of theory.
~ 37~35 Example 116:
The procedure descr;bed in Example 113 is repeated, except that 7.89 ml (100 mmol) of ethylene glycol monomethyl ether are used in place of n-pentyl alcohol. After 8 hours at 180C, the mixture is ~orked up in accordance with Example 113. The product is then recrystallised from 50 ml of n-hexane. This gives 2.8 g (11.8 mmol) of 1 phenyl-2-methoxymethylbenz;midazole as light brown crystals of melt-ing point 70.3C, corresponding to a yield of 24% of theory~
Example 117:
The procedure described in Example 114 is repeated~
except''that 13.0 ml (150 mmol~ of furfuryl alcohol and 0.33 g (3.2 mmol) of l;th;um acetate-dihydrate are used in place of azobenzene and sod;um acetate. After 8 hours at 130, the mixture is distilled as ;n Example 114 and the product ;s recrystall;sed from 100 ml of cyclohexane. Th;s gives 4.3 9 (16.5 mmol) of 1-phenyl-2-(2-furanyl)-benz;midazole as light brown crystals of melt;ng po;nt 12~.9C, corresponding to a y;eld of 33% of theory.
Example 118:
The procedure descr;bed in Example 117 is repeated, except that 15.5 ml (150 mmol) of benzyl alcohol are used in place of furfuryl alcohol. After 8 hours at 180C~ the solvent is removed and the residue is subjected to chromato-graphy on silica gel in ether/d;chloromethane. Two recrys-tall;sat;ons from 100 ml and 150 ml of n hexane give 3.0 g (11.1 mmol) of 1~2-diphenylbenzimidazole as white crystals of melting point 111.7a, corresponding to a yield of 22%
of theory.
Example 119:
30 ml of n-butanol are in;t;ally ;ntroduced ;nto a pressure tube, and carbon monoxide is passed ~hrough. 10.50 g ~50 mmol) of 4,4'-dimethylazobenzene, 4~1 9 (53 mmoi~ of sodium acetate, 0~1308 9 ~0.5 mmol) of ruthenium tr;chloride-tr;hydrate and 0.524 g (2 mmol) of triphenylphosphine are added, and the tube ;s sealed under carbon monox;de at normal pressure. After 8 hours at l~OoC~ the solvent is removed~
~3~79L3~
and the product ;s distilled in vacuo and then recrystallised from 20 ml of n-pentane. This gives 6.6 9 (25 mmol) of 1-(4'-methylphenyl)-2-n-propyl-6-methylbenzimidazole as white crystals of meltin~ point 88.8C, corresponding to a yield of 50~ of theory.
Example 120:
The procedure described in Example 119 is repeated, except that 10.9 g ~50 mmol) of 4,4~-difluoroazobenzene are used in place of dimethylazobenzene~ After 8 hcurs at 180C, the product is distilled as in Example 119 and then recrys-tallised from 30 ml of n-pentane~ This gives 3.71 9 ~13.b mmol) of 1-(4'-fluorophenyl)-2-n-propyl-6-fluorobenzimidazole as yellow crystals of melt;ng point 75.3, correspondlng to a yield of 27% of ~heory.
Example 121:
The procedure described in Example 119 is repeated, except that 12.55 9 t50 mmol) of 4,4'-dichloroazobenzene are used in place of dimethylazobenzene. After 8 hours at 180C, the product is distilled in accordance with Example 11g and subjected to chroma~ography on silica gel in dichloromethane~
After recrystallisation from 50 ml of n-hexane9 this gives 1.2 g t3.9 mmol) of 1-t4'-chlorophenyl)-2-n-propyl-6-chloro benzimidazole as white crystals of melting point 100.2~
corresponding to a yield of ~X of theory.
Example 122:
The procedure described in Example 114 is repeated~
except that 12.55 9 tS0 mmol) of 4,4'-dichloroazobenzene and 11.21 ml ~150 ml) of n-propanol are used in place of azo-benzene and n-heptanol. After 8 hours at 180C and dist;l-lation in accordance with Example 114, the product is recrys~
tallised from a mixture of 100 ml of cyclohexane and 150 ml of n-hexane. This g;ves 4.8 g ~16.5 mmol) of 1 t4'-chloro-phenyl)-2~ethyl-6 chlorobenzimidazole as white crystals of melt;ng point 141.3C, corresponding to a yield of 33% of theory.
Example 123:
The procedure described in Example 114 is repeated, 3L;~37~3~i except that 10.5 9 (50 mmol) of 4,4'-dimethylazobenzene and 11.89 ml (150 mmol) of hydroxymethylcyclopropane are used in place of azobenzene and n-heptanol. After 8 hours at 180C
and distillation in accordance with Example 114, the product is subjected to chromatography on siLica gel in ether and then recrystallised from 50 ml of n-hexaneO This gives ~.02 9 ~23.0 mmol) of 1-(4'-methylphenyl)-2-cyclopropanyl-6-methylbenzimidazole as white crystals of melting point 93.6C, corresponding to a y;eld of 46~ of theory.
Example 124:
.
The procedure described in Example 122 is repeated, except that 9.8 9 (50 mmol) of 4 methylazobenzene are used in place of dichloroazobenzene. After 8 hours at 180C and distillation in accordance with Example 122~ this gives 8.8 g ~37.3 mmol) of a mixture of isomers, which consists of 60%
o~ 1-t4'-methylphenyl)-2-ethylbenzimidazole and 40% of 1-phenyl-2 ethyl-6-methylbenz;midazole, as a yellow Oilf cor~
responding to a total yield of 75% of theoryD
Example 125:
The procedure described in Example 122 is repeated, except that 10.0 g (50 mmol) of 4-fluoroazobenzene are used in place of dichloroazobenzene. After 8 hours at 180C and distillation in accordance with Example 122, this gives 7.9 9 (32.9 mmol) of a mixture of isomers, which consists of 50%
each of 1-~4'-fluorophenyl)-2-ethylbenzimidazole and 1-phenyl-2-ethyl-6-fluorobenzimidazole, as a yellow oil, correspond-ing to a total yield of 66% of theory Example 126~
The procedure described in Example 122 is repeated, except that 10.8 g (50 mmol) of 4-chloroazobenzene are used in place of dichloroazobenzene. After 8 hours at 180C
and distillation in accordance with Example 122~ this gives 3.4 g t1303 mmol) of a mixture of isomers~ wh;ch consists of 53% of 1-~4'-chlorophenyl)-2-ethyl-benzimidazole and 4~ of 1-phenyl-2-ethyl-6-chlorobenzimidazole, as a yellow oil, corresponding to a total yiPld of 27% of theoryO
- 27 - ~ ~37435 Example 127:
The procedure described in Example 122 is repeated, except that 13.05 9 (50 mmol) of 4-bromoazobenzene are used in place of dichloroazobenzene. After ~ hours at 180C and distillation in accordance with Example 122, this gives 3.1 9 (10.3 mmol) of a mixture of isomers, which consists of 43% of 1-(4'-bromophenyl)-2~ethylbenzimidazole and 57% of 1-phenyl-2-ethyl-o-bromobenzimidazole, as a yellow oil~
corresponding to a total yield of 21%~
Example 128:
The procedure described in Example 11~ is repeated, except that 6.0 g (26 mmol) of 3,5,3'-trimethyla~obenzene,
~37a~3~
Under the applicable reaction conditions, the azo-ben~ene can also be replaced by corr,esponding N'-phenylated o-phenylenediamines.
The catalysts are preferably used in quantities of .001 to 20 mol %, ;n particular 0~01 to 10 mol ~ and especi-ally 0.0~ to 5 mol ~. These can be heterogeneous catalysts, for example ruthenium on a suitable support material such as carbon, or preferably homogeneous catalysts which are soluble in the reaction mixture. Examples of homogeneous catalysts are compounds of ruthenium or rhodium, in particular their salts of inorganic or organ;c ac;ds, and complex compounds thereof. The complexes can be mononucLear or poLynuclear and they can contain polyfunct;onal, preferably monofunct;onal l;gands. Such ligands are descr;bed, for example~ in Ad-vanced Inorganic Chemistry, 4th Edition, published by Wiley New York (1980), pages 107 to 194. The compounds or com-plexes can be in any oxidation stages of the ruthen;um or rhodium; the preferred oxidation stages are 0~ 1, 2, 3 and 4.
Suitable salts of ruthenium or rhodium are der;ved, for example~ from the following acids: formic acid~ acetic acid, benzoic acid, toluenesulfon;c acid, phosphoric acid, sulfuric acid, perchlor;c acid and hydrofluoric, hydrobromic, hydriodic and in particular hydrochloric acid. The salts can also be used in their hydrated form. Ruthenium trirhloride tr;hydrate and rhodium tr;chloride-trihydrate are particu larly preferred~
Amongst the complexes, those with carbonyl ligands are particularly preferred. Dodecacarbonyl-triruthenium is one example. In a preferred embodiment of the proGess accor-ding to the invention, the carbonyl complexes are formed be-fore or during the reaction from, for example, the abovemen-tioned salts, by carry;ng out the reaction under a pure car-bon monoxide atmosphere or under mixtures of carbon monoxide with an inert blanket gas, for example9 ni~rogen or a rare gas, such as helium or argon.
Further l;gands are compounds with donor atoms, for _ 7 _ ~ ~3~4~
example P~ N, As, Sb, B;, O, S and Se, and anions of or-ganic or ;norganic ac;ds~ Examples are the arsines, sti-b;nes, bismuthines and in particular the phosphines. Further examples of l;gands are fluor;de, brom;de, chloride, iodide~
hydride, the trichloro-tintII) anion, dimethyl sulfoxide, nitrosyl, the acetate anion and the acetonyl acetate anion.
Ligands with tr;valent elements of the fifth ma;n group of the periodic table are ;n part;cular am;nes, phosphines~
ars;nes, st;b;nes and b;smuth;nes, espec;ally those with aryl radicals, for example phenyl which can be substituted by halogen ~F, Cl), C1-C4-alkyl or C1-C4-alkoxy. Further radicals are alkyl having preferably 1 to 12 C atoms, yclo-alkyl, for example cyclohexyl, and aralkyl, for example benzyl~ The phosphines are the preferred ligands from this group. Examples are:
Triphenylphosphine~ tri-~o-toluyl)-phosphine, tri-~p-toluyl)-phosphine, tri-(p-fluorophenyl)-phosphine, tri-tp-methoxyphenyl)-phosphine, tertiary~butyldiphenylphosphine, ~ricyclohexylphosphine, tetraphenyldiphosphine~ triphenyl-amine and tr;phenylstib;ne. Phosphites are also suitableO
in particular those ~ith aryl radicals such as phenyl. Tri-phenyl phosphite is an example. The complexes can conta;n identical or different ligands. Preferably, the compl~xes conta;n phosph;ne ligands and CO l;gands.
The complexes can be added as isolated compounds at the beginn;ng of the reaction. It has proved to be expe-dient to prepare the complexes before the start of the re-action from ruthenium or rhodium compounds ~for example their salts~ by adding the ligand-forming compounds, if appropriate in a CO atmosphere, and then to proceed with the process accord;ng to the invention by adding the reactants.
The ligand-form;ng compounds can be added in equi-molar amounts or in excess~ The molar ratio of the ruthenium or rhodium compounds and the ligands is preferably 10:1~ in particular 6 to 2~
In a preferred embodiment of the process, ruthenium or rhodium compounds~ in particular ~heir halides, are em-~2379L35 -- 8 --ployed as a reactant, if ~ertiary amines having at least one RCH2- group are used, and advantageously the reaction is additionally carried out under a C0 atmosphere.
In a further preferred embodiment of the process, ruthenium complexes, preferably those with phosphine ligands, are employed as reactants, if primary alcohols, or esters thereof, of the formula III are used, the reaction espe-cially being carr;ed out addit;onally under a C0 atmosphere.
It has also proved to be advantageous~ if reactants of the formula III are used, to add a basic compound in addit;on, in order to obtain higher yields. The quantity is pre~erably 0.1 mol %, pre~erably 0.1 to 6û and in particular 0.1 - 20 mol ~ relative to the azobenzene of the formula IIu Examples of suitable basic compounds are primary, secondary and espec;ally tert;ary am;nes, includ;ng those of the formula IV. Amines of the formula IV are preferably added in catalytic quantities, for example in quantities of 0.1 to 2~ mol X, relative to the azobenzene of the formula II. Examples of further amines are methylamine, dimethyl-amine, tr;methylamine~ cyclohexylamine, cyclohPxyldimethyl-amine, morphol;ne, N-methylmorpholine, piperidine~ N-methyl-p;per;dine, pyrrolidine, N-methylpyrroLidine and benzyldi-methylamine.
Further suitable basic compounds are metal salts of carboxylic acids, in part;cular alkal;ne earth metal s~lts~
for example calcium and strontium salts, and especially the alkali metal salts of carboxylic acids. Potassium and in particular sodium and lithium are the preferred alkali metals.
Examples are:
Sod;um bicarbonate~ lithium acetate, lithium pro-pionate, lithium formate, lithium benzoate, sodium acetate and sodium benzoate~
The reactants can be employed in equimolar quanti-ties, or an excess of tertiary amines having at least one RCH2- ~roup or of a primary alcohol or its carboxylic acid ester can be used~ The excess selected can be such that these reactants serve at the same time as the sol~ent~ Of ~23~3~
_ 9 _ course, mixtures of the abovementioned reactants can also be employed.
If equ;molar quantities or a small excess are em-ployed, an inert soLvent ;s advantageously also used. Polar aprotic solvents are part;cularly suitable. N-alkylated ac;d amides are preferred. In view of the reaction tempera-tures, higher-boiling solvents are also preferred, in order to enable the process to be carried out under normal pressure.
Examples of solvents are: hydrocarbons, such as benzene, toluene, chlorobenzene, dichLorobenzene, benzo-nitrile and tetral;n, ac;d esters, such as ethylene carbonate, tr;ethyl phosphate and ethyl benzoate, sulfones, such as tetramethylenesulfone, sulfoxides, such as dimethyl sulfoxide, tertiary amines, such as diphenylmethylam;ne, cyclohexyldi-methylamine and N-methylpiper;d;ne, ethers~ such as d;oxane, d;ethylene glycol dimethyl or diethyl ether and triethylene glycol dimethyl ether, and linear or cycl;c N-alkylated acid am;des, such as tetramethylurea, dimethylformamide, dimethyl-acetamide, d;ethylacetamide, N-methylpyrrolidoneO N--formyl-morpholine, N-~ormylpiperidine and hexamethyl-phosphoric acid triamide. The preferred solvents are diethylformamide, dimethylacetamide~-N-formylmorpholine and in particular te~ra-methylurea and 1,3-dimethyl-2-imidazolidone.
The process is carried out in apparatus conventional for this purpose, by mixing the reactants, the catalys~ and~
if appropriate, a solvent and then heating the react;on mix-ture to the desired reaction temperature. This is prefer-ably 120 to 230C, in particular 15~ to 230C and especially 150 to 200C. The process can be carried out under normal pressure or elevated pressure.
The benzimidazoles of the formula I are isolated in the convent;onal manner, for example by crystallisation or distillation a~ter removal of the solvent.
The process accord;ng to the invention gives, by means of a novel reaction, 1,2-substituted benzimidazoles in good yields and good purity from readily accessible and in-expensive startin~ materials. The 1,2~substituted ben~imi-~3~35 dazoles can be used especially as leaf fung;cides.
The examples wh;ch follow explain the invention in more detail. The yields refer to the azobenzene employed.
Example 1:
12.5 ml of tetramethylurea are init;ally introduced into a reflux apparatus equipped with a thermometer, gas in-let tube and bubble counter. Carbon monoxide under normal pressure is passed through with stirring, and ~.55 9 (25 mmol) of azobenzene, 2.98 ml (1~.5 mmol) of tri-n butylamine and 0.0654 9 ~0.25 mmol) of ruthen;um trichlor;de-tr;hydrate are added. The reaction mixture is heated for 17 hours under reflux (175-177), carbon monoxide being continuously passed through. After removal of the solvent, the mixture is then dist;lLed off in vacuo. This gives 1.64 9 (6.95 mmol) of 1-phenyl~2-n-propylbenzimidazole as a yellow oil, corres-ponding to a yield of 56X of theory, relative to tri-n-butyl-amine, bo;ling point 145-~48/0.2 mm Hg.
Example 2:
The procedure described in Example 1 is repeated, except that 50 ml of tetramethylurea~ 18.2 9 (100 mmol) of azobenzene, 23.86 ml (100 mmol) of tri-n-butylam;ne and 0~2615 9 (1 mmol) of ruthenium trichloride-trihydrate are used. After 8 hours' reflux (175-178), the mixture is worked up as in Example 1. This gives 14.1 g tS9.7 mmol) of 1-phenyl-2-n-propylbenzimidazole as a yellow oilD correspon-ding to a y;eld of 60% of theory.
Examples 3-19:
rhe procedure described in Example 1 is repeated, except that 12.5 ml of solvent, 4~55 g ~25 mmol) of azo-ben2ene, 5.96 ml ~25 mmol) of tri-n-butylamine and 0.0654 9 ~0.25 mmol) of ruthenium trichloride-~rihydra~e are used.
After a reaction period of 6 hours at 170, the yield is determined by gas chromatography. The results are listed in the table.
~;~3~7~3~i Example No. Solvent __ _ Yield 3 Tetramethylurea 39 4 Diethylformamide28 N-Formylmorphol;ne25 6 N-Formylpiperidine14 7 Dimethylacetamide46 8 DiethyLacetamide12 9 N-Methylpyrroli done 19 Hexamethylphosphoric acid triamide 8 11 Sulfolan 22 12 Dimethyl sulfoxide 9 1~ Ethylene carbonate 9 14 Triethyl phosphate 10 ~enzonitrile 7 16 o-Dichlorobenzene26 17 Diethylene glycol ethyl ether 12 18 Tetralin 14 19 Tri-n-butylamine 14 .
* Reflux at 165-167 Examples 20 23:
The procedure described in Example 3 is re-peated, but under reflux conditions and with the volumes of tetramethylurea ~TMU) and reaction times given in the table. The yield is determined by gas chromatography~
~%~
21 12.5 10 67 22 6~25 10 ~ 34 Examples 24 -_26:
The procedure described in Example 3 is repeatedD
except that N-formylmorphol;ne is used as the solvent, and at the temperatures given in the table. The yield is deter-mined by gas chromatography.
3L~37435 Example No. _Temperature tC) Yield (%) 2$ 190 52 . .
Examples 27-28:
The procedure described in Example 21 is repeated, except that the quantities of tri-n-butylam;ne given in the table are employed. The yield is determined by gas chroma-tography.
Example No~ Tri-n-butylamine tmmol) Yield tX) 27 31.25 45 28 3?~5_ _ 45 Examples 29-36:
The procedure described in Example 21 is repeated, except that ;n each case 1 mol X of ruthenium trelative to azobenzene) is used as the catalyst in the form of the com-pounds indicated in the table. To illustrate the effect of carbon monoxide, the experiments are also carried out with argon being passed through instead of carbon monoxide~ The yield is de~ermined by gas chromatography.
Example No. Catalyst Yield ~X) - _ _ _ under C0 Unde_r Ar 29 RuCl3 3 HzO ~7 RuCl~3H20 9 31 RU3tCO)12 32 RU3(CO)12 33 Ru(oAc)2(pph3)2 24 34 RU(oAc)2tpph3)2 CRu2SOAc)4~Cl 58 36 CRu2tOAc)4]Cl 10 Examples 37-44:
The procedure described in Example 21 is repeated~
except that in each case 1 mol X (relati~e to a~obenzene) of the ruthenium compounds and complex formers indicated in the table are used as the catalyst. The yield is determined by gas chromatography.
~3~435i Exarnple No. CataLyst Yield (S~) 37 RuCl2 tDMSO)4 73 38 Ru(acac)3 17 39 RuCl33HzO ~ 2 AsPh3 67 RuCl33H20 + 2 SbPh3 49 41 RuCl33H20 + 2 Pph3 47 42 RuCl33H20 ~ 2 P(Oph)3 66 43 RuCl33H20 ~ Ph2PCH2CH2Pph2 8 44 RuCl33H20 + 2 PMe3 5 Example 45:
The procedure described in Example 21 is repeated, ex-cept that 0.00654 9 S0.025 mmol) of ruthenium trichloride-trihydrate is used. After a reaction time of 24 hours, 0.65 9 t2.75 mmol) of 1-phenyl-2-n-propylbenz;midazole, correspon-ding to a yield of 11% of theory, ;s obtained.
Example 46:
The procedure described in Example 21 is repeated, except that 18.2 9 t100 mmol) of azobenzene, 18~95 ml t100 mmol) of tri-n-propylamine, 0.2615 9 (1 mmol) of ruthenium trichloride-trihydrate and 50 ml of tetramethylurea are used.
After 16 hours under reflux conditions t162-164), the solvent is removed and the product is distilled in vacuo. Th;s gives 6.5 9 t29.3 mmol) of 1-phenyl-2-ethylbenzimidazole as a yellow oil of boiling point 148-15ZC/0.35 mm llg, corres-ponding to a yield of 29% of theory.
The procedure described in Example 46 is repeated, except that 17.33 ml t100 mmol) of n-hexyldimethylamine are used in place of tri-n-propylamine. After 23 hours under reflux conditions, the solvent is removed and the product ;s distilled in vacuo Th;s gives 5.34 9 t2û.~ mmol~ of 1-phenyl-2-n-pentylbenzimidazole as a yello~ oil of boiling point 160-161C~0.6 mm Hg, corresponding to a yield of 20%
of theory~
The procedure described in Example ~6 is repeated, 37~3S
except that 21.0 9 (100 mmol3 of 4,4'-dimethylazobenzene and 18.56 9 (100 mmol) of tr;-n-butylamine are used in place of azobenzene and tri-n-propylamine. After 23 hours under reflux conditions ~178), the solvent is removed and the product is distilled ;n vacuo. It ;s then subjected to chromato-graphy on silica gel in ether and the ether is removed. The product is recrystallised from 100 ml of pentane. This gives 12.5 g (47.3 mmol) of 1-(4'-methylphenyl)-2-n-propyl-6-methylbenzimidazole as white crystals of melting point 88.8C, corresponding to a yield of 47% of theory.
Example 49.
The procedure of Example 47 is repeated, except that 26.95 g (100 mmoL) of tri-n-hexylamine are used in place of n-hexyldimethylamine~ After 8 hours under reflux conditions (1~0C) and working up in accordance ~ith Example 47, this gives 4.45 g (16.9 mmol3 of 1-phenyl-2-n-pentylbenzimidazole as a yellow oil of boiling point 160-161C/O.o mm Hg, cor-responding to a yield of 17X of theory.
Example 50:
The procedure described in Example 48 is repeated, except that 25.1 9 (100 mmol) of 4,4'-dichloroazobenzene are used in place of dimethylazobenzene. After 23 hours under reflux conditions ~180) and distillation as ;n Example 48, the product is recrystallised from 30 ml of n-hexane.
This gives 2.98 g (9.8 mmol~ of 1-(4'-chlorophenyl~-2-n-propyl-6-chlorobenzimidazole as lig~t brown crystals of melting point 100.2C~ corresponding to a yield of 10~ of theory.
Example 51:
The procedure described in Example 48 is repeated, except that 21~8 9 (100 mmol) of 4,4'-difluoroazobenzene are used in place of dimethylazobenzene. After 23 hours under reflux conditions and distillation in accordance ~ith Ex-ample 48, the product is recrystallised from 130 ml oF ~-pentane. This gives 9.17 g ~33.7 mmol) of 1-(4'-fluorophenyl)-2~n-propyl-6~fluorobenzimidazole as white crystals of melt-ing point 75.3C, corresponding to a yield of 34~ of theory.
~37~
Example 52 The procedure described in Example 1 is repeated, except that 11.9 9 (S0 mmol) of 3~3',5~5'-tetramethylazo-benzene, 9.18 g t50 mmol) of tri~n-butylamine, 0.131 9 (D~S
mmol) of ruthenium trichloride-trihydrate and 25 ml of tetra-~ethylurea are used. After 9 hours under reflux conditions (80-181), the solvent is removed and the product is dis tilled in vacuo. Two recrystallisations from 50 ml of n-hexane each time give 3.04 9 (10.~ mmol) of 1-(3',5'-dimethyl)-2-n-propyl-4,6-dimethylbenzimidazole as white crys~als of melting point 118.3C, corresponding to a yield of 21X of theory.
Example 53:
The procedure described in Example 52 is repeated~
except that 11.53 g ~50 mmol) of 4-chloro-4'-methylazoben-zene are used ;n place of tetramethyla20benzene. After 12 hours under reflux conditions tl80C) and d;stillation as in Example 52~ the product is recrystallised tw;ce from 50 ml of n-pentane. This gives 5.0 9 (17.6 mmol) of a mixture of isomers, which consists of 94% of 1-(4'-methylphenyl)-2-n-propyl-6-chlorobenzimidazole and 6% of 1-t4'-chlorophenyl)-2-n-propyl-6-methylbenzimidazole~ as yellow crystals~ corres-ponding to a total yield of 35X of theory. After a further recrystallisation from S0 ml of n-hexane, the pure main iso-mer of the product is obtained as white crystals of melting point 92.9C in 3 yield of 20% of theory.
Example 54:
The procedure described in Example 52 is repeated, except that 10.7 9 ~50 mmol) of 4-fluoro-4'-methylazobenzene are used in place of tetramethylazobenzene~ After 23 hours under reflux conditions (17~-18~C) and distillation in accordance with Example 52, the product is recrys~allised twice from 50 ml of n-pentane. This gives 4.3 9 ~16.1 mmol) of a mixture of isomers, which consists of 71% of 1-~4'-methylphenyl)-2-n-propyl-6-fluorobenzimidazole and 29% of 1-(4'-fluoromethyl)-2-n-propyl-6-methylbenzimidazole, as ~hite crystals, corresponding to a total yield of 32% of - 16 ~237~35 theory~ After a further recrystall;sation from 50 ml of n~hexane, the pure main isomer of the product is obtained as white crystals of melt;ng point 86.7 ;n a yield of 15~ of theory.
ExampLe 55:
The procedure described in Example 52 ;s repeated, except that 13.3 9 t50 mmol) of 4-methyl-4'-ethoxycarbonyl-azobenzene are used in place of tetramethylazobenzene. After 23 hours under reflux conditions (180C) and dist;llation in accordance w;th Example 52~ the product is subjected to chromatography on s;l;ca gel in ether. After removal of the ether, the product ;s recrystallised from 55 ml o~ n-hexane.
This gives 2.27 9 t7.05 mmol) of 1-(4'-methylphenyl)-2-n-propyl-6-ethoxycarbonylbenzimidazole as white crystals of melting point ~0.2C, corresponding to a yield o~ 14% of theory.
Example 56:
The procedure described in Example 1 is repeated, except that ~.5 9 ~36 mmol) of 3,5-dichloro-4'-methylazo-benzene, 6.61 g (36 mmol) of tri-n-butylam;ne, ~.094 9 (0.36 mmol) of ruthenium trichloride-trihydrate and 18 ml of tetra-methylurea are used. After 23 hours under reflux conditions (177-180C), the solvent is removed and the product is d;st;lled ;n vacuo and then recrystallised once from 50 ml of cyclohexane and once from a mixture of 50 ml of hexane and 25 ml of cyclohexane. This gives 2.3 g t7.2 mmol) of 1-t3',5'-dichlorophenyl)-2-n-propyl-6-methylbenzim;dazole as white crystals of melting point 16~.6C~ corresponding to a yield of 20% of theory.
Example 57:
The procedure described in Example 52 is repeated, except that 1~.9 g (50 mmol) of 404'-difluoroazobenzene and 8.15 9 t50 mmol) of dimethyl-t3-phenyl-n-propyl)-amine are used in place of tetramethylazobenzene and tri-n-butylam;ne.
After 22 hours under reflux conditions (18~~) and distil lation in accordance with Example 52, the product is recrys~
tallised twice from 75 ml of n-hexane~ This gives 2.6 9 ~23~3S
(7.8 mmol) of 1-~4'-fluorophenyl)-2-(2-phenylethyL)-6-fluoro-benzimidazole as white crystals of melting point 111.7C, corresponding to a yield of 16~ of theory.
Example 58:
The procedure described in Example 57 is repeated, except that 7.05 9 (50 mmol~ of dimethyl-~cyclohexylmethyl)-amine are used in place of dimethyl-(3-phenyl-n-propyl)-amine. After 22 hours under reflux conditions (175 180C) and distillation in accordance with Example 52, the product is recrystallised twice from 50 ml of pentane. This gives 1.85 9 (5~9 mmol) of 1-(4'-fluorophenyl)-2-cyclohexyl-6-fluoro-benzimidazole as yellow crystals of melting point 115.1C, corresponding to a yield of 12X of theory.
ExampLe 59:
The procedure described in Example 57 is repeated, except that 6.95 9 (50 mmol) of dimethyl-(3-cyclohexenyl-methyl)-amine are used in place of dimethyl-(3-phenyl-n-propyl)-amine. After 23 hours under reflux conditions (17~-180C) and d;stillation in accordance with Example 52, the product is recrystallised once from 100 ml of n-pentane and once from 80 ml of n-pentane. This gives 1.04 g ~3.35 mmol3 of 1-(4'-fluorophenyl)-2-t3-cyclohexenyl)-6-fluorobenzimid~
azole as white crystals of melting point 100.1C, correspond-ing to a yield of 7% of theory.
The procedure described in Example 46 is repeated, except that 21.0 9 ~1~0 mmol) of 4,4'-dimethylazobenzene are used in place of azobenzene. After 72 hours under reflux conditions t161-164C), the product is distilled in accor-dance with Example 46 and then recrystallised from ~0 ml of n-hexane. This gives 10.0 g (40 mmol) of 1-(4'-methylphenyl~-2-ethyl-6-methylbenzimidazole as white crystals of melting point 84.0C~ corresponding to a yield of 40% of theory.
~e~
The procedure described in Example 4O is repeated, except that 19.6 9 (1~0 mmol) of 4-methylazobenzene and 18.56 ~ (100 mmol) of tri-n-butyla~ine are used in place of ~ 237~L35i azobenzene and tri-n-propylamine. After 22 hours under reflux condit;ons (178-180C), 100 ml of 2N hydrochloric ac;d are added to the reaction mixture which is then extrac-ted twice with 100 ml of ether. The aqueous phase is ren-dered alkaline w;th 110 ml of 2N sodium hydroxide solution and extracted three times with 100 ml of ether. After dry-ing of the extract with magnesium sulfate and removal of the ether, the crude product is subjected to chromatography on silica gel in ether. After removal of the ether and distil-lation in ~acuo, the product is recrystallised from 100 ml of n-pentane. This gives 11.1 9 ~44.4 mmol) of a mixture of isomers, ~h;ch cons;sts of 71~ of 1-~4' methylphenyl~-2-n-propylbenzimida~ole and 29% of 1-phenyl-2-n-propyl-6-methyl-benzimidazole, as white crystals, corresponding to a total yield of 44% of theory.
Example 62:
The procedure descr;bed ;n Example 46 is repeated, except that 21.~5 9 ~10n mmol~ of 4-chloroazobenzene are used ;n place of azobenzene. After 8 ho~rs under reflux condit;ons (178C) and workîng-up in accordance ~;th Ex-ample 61, the product is dist;lled once more. This gives 10.~ 9 (38.4 mmol~ of a mixture of isomers, which consists of equal parts of 1-t4'-chLorophenyl)-Z-n-propylbenzimidazole and 1-phenyl-2-n-propyl-6-chlorobenziMidazole, as a yellow oil~ corresponding to a total yield of 38% of theory.
Example 63~
The procedure described in Example 52 is repeatedO
except that 10u5 9 t50 mmol) of 3,3'-d;methylazobenzene are used in place of tetramethylazobenzene~ After 22 hours under reflux cond;tions (179-180C), the product is distilled in accordance with Example 52 and recrystall;sed twice from 50 ml of n-hexane. This gives 3.2 9 (12u1 mmol) of a mix;
ture of ;somer~, which consists of 71% o~ 3'-me~hylphenyl~-2-n-propyl-7-methylbenzimidazole and 29~ of 1-(3'-methyl-phenyl)-2-n-propyl-5 methylbenzimidazole~ as white crystals~
corresponding to a total y;eld of 24~ of theory.
~L~3~3 Example 64:
The procedure described in ExampLe 52 is repeated, excep~ that 11.~ g ~50 mmol) of 4-methyl-4'-methoxya20benzene are used ;n place of tetramethylazobenzenel After 23 hours under reflux conditions ~180C) and d;stillat;on in accor-dance with Example 52, the product is subjected to chroma-tography on s;l;ca gel in ether. After removal of the ether, the product is recrystallised from 50 ml of n-pentane. This g;ves 1.92 9 ~6.9 mmol) of a mix~ure of isomers, which con-s;sts of 80~ of 1-~4'-methoxyphenyl)-2-n-propyl-6-methyl-benzimidazole and 20% of 1-~4'-methylphenyl)-2-n-propyl-6-methoxy-benzimidazoler as white crystals, corresponding to a totaL yield of 14% of theory.
Example 65:
The procedure descr;bed in Example 21 is repeated~
except that 1 g of 5% of ruthenium on active charcoal is used as the catalyst in place of ruthenium trichloride-tri-hydrate. After 8 hours under reflux conditions, this gives 0.3 9 (1.3 mmol) of 1-phenyl-2-n-propylbenzimidazole, cor-responding to a yield o~ 5X of theory.
Example 66:
The procedure described in Example 21 is repeated~
except that 4.60 9 ~25 mmol) of N-phenyl-o-phenylenediamine are used in place of azobenzene. After 4 hours under reflux conditions and after distillat;on, this gives 3~12 9 ~13.2 mmol) of 1~phenyl-2-propylbenzimidazole as a yellow oil, corresponding to a yield of 53% of theoryu Example 67:
The procedure described in Example 21 is repeated, except that 0.0659 9 ~0.25 mmol) of rhodium trichloride tri-hydrate are used in place of ruthenium trichloride-trihydrate~
After 8 hours under reflux conditions, this gives 1.65 9 ~7.0 mmol) of 1-phenyl-2-n propylbenzimida~ole, corresponding to a yield of 28%.
Examples 68-71:
14.8 ml of n-butanol are initially introduced into a pressure tube, and carbon monoxide is passed through with :L~37~L3S
st;rring. 4.55 g (25 mmol) of azobenzene, 2.05 g (25 mmol) of sodium acetate, 0.0654 g (0.25 mmol) of ruthenium tri-chloride-trihydrate and 0.262 9 (1 mmol) of tr;phenylphos-phine are added, and the tube is sealed under carbon monoxide.
After stirring for 8 hours at the temperatures indicated in the table, the 1-phenyl-2-n-propylbenzimidazole formed is determined by gas chromatography.
Example ~o~ Temperature ~C)Yield (%) Examples 72-76:
The procedure described in Example 6~ is repeated~
except that the bases indicated in the table are used~ The yields are determined by gas chromatographyO
Example NQ. Base Yield (%) 72 Sodium benzoate 31 73 Lithium acetate-dihydrate*55 74 Tri-n-butylam;ne 58 N-benzyldimethylamine 69 76 Sodium bicarbonate 20 * 16 mmol Examples 77-80:
The procedure described in Example 73 is repeated~
except that 4.57 ml (5~ mmol) of n-butanol and 12.5 ml of the solvents ind;cated in the table are usedO The yields are determined by gas chromatography.
Example No. Solvent _ Yield (%) 77 N~N dimethylformamide 6 78 N,N-dimethylacetamide 53 79 ~-methylpyrrolidone 64 Tetramethylurea 65 1;~37~L3~;
Examples 81-85:
The procedure described in Example 80 is repeated, except that the quant;ties of tr;phenylphosph;ne ;nd;cated in the table are usedn The y;elds are determ;ned by gas chromatography.
Example No. mmol of tr;phenylphosph;ne_ Yield (X) 82 0.75 63 84 1.25 69 1.5 3~
.. ~ .
Examples 86-90:
The procedure descr;bed ;n Example 83 is repeated~
except that the quantit;es of l;thium acetate-dihydrate in-dicated in the table are used. The yields are determ;ned by gas chromatography.
Example No. mmol of lithium aceta~e-d;hydrate Y;eld ~%) 86 0 ~6 87 1.6 64 8~ 4 65 .
Examples 91-94.
The procedure described in Example 87 ;s repeated, except that the quantities of n-butanol indicated in the table are used. The y;elds are determined by gas chromato-graphy.
Example ND. mmol of n-butanol Yield (X?
~2 5~ 72 93 75 6~
_ 94 125 69 Examples 95-97:
The procedure descr;bed in xarnple 90 ;s repeated, except that 6D86 ml ~75 mmol) of n-butanol and the quantities of ruthenium ~r;chloride-trihydrate and triphenylphosph;ne ~;~3~
(Pph3) indicated in the table are used. The yields are determined by gas chromatography.
Example No. mmol of RuCl3 3H20 mmol of Pph3 Y;eld ~%
00125 0~5 62 96 O.û5 0.2 26 97 _ __ 0 025 _ 0.1 19 Examples 98 107:
The procedure described in Example 95 is repeated~
except that 0.165 9 ~1.6 mmol) of lithium acetate dihydrate is used and the ligands indicated in the table are used in place of triphenylphosphine. The yields are determined by gas chromatography~
Example No. Ligands ~0~5 mmol)Yield ~X) 98 Tris-~o-tolyl)-phosph;ne 36 99 Tr;s-tp-tolyl)-phosphine 58 100 Tris-~p-fluorophenyl)-phosphine 53 101 Tris-(p-methoxyphenylj-phosphine 55 102 Triphenyl phosph;te 6 103 Tris-n~butylphosphine 2 104 t-Butyldiphenylphosphine 41 105 Tricyclohexylphosphine 11 106 Bis-~diphenyLphosphine~-methane*11 107 Bis-~diphenylphosphine)-butane* 8 * 0.25 mmol Examples 108-112:
The procedure described in Example 93 is repeated, except that the quantities of sodium acetate indicated in the table are used in pLace of lith;um acetate-dihydrate.
The yields are determined by gas chromatography.
Example No. mmol of sodium acetate Yield ~%) 108 û.25 21 111 1~25 53 112 __ 2.5 _ _ _ 48__ _ Example 113 25 ml Qf tetramethylurea are initially introduced ~37~3~
into a pressure tube, and carbon monoxide ;s passed through.
9.1 9 (50 mmol) of azobenzene, 10.8 ml t100 mmol) of n-pentyl alcohol, 3.3 9 ~32 mmol) of lith;um acetate-dihydrate, 0.1308 g (0.5 mmol) of ruthenium trichloride-~rihydrate and 0.524 9 (2 mmol) of triphenylphosphine are added. The tube is sealed under carbon monoxide and st;rred for 8 hours at 180C. After removal of the solvent, the product is dis-tilled in vacuo, subjected to chromatography on silica gel in dichloromethane and then recrystallised from 50 ml of pentane. This gives 3.7 9 (14.8 mmol) of 1-phenyl-2-n-butyl-benzimidazole as white crystals of melting point 59.6C, corresp`onding to a yield of 30% of theory.
Example 114:
25 ml of tetramethylurea are initially ;ntroduced into a pressure tube, and carbon monox;de ;s passed through.
9.1 9 ~S0 mmol) of azobenzene, 21.17 ml (150 mmol3 of n-hep-tanol~ 0.123 g (1.5 mmol) of sodium acetate, 0.1308 9 (0.5 mmol) of ruthen;um trichlor;de-trihydrate and 0.524 g (~ mmol) of triphenylphosphine are added, and the tube is sealed under carbon monoxideO After 8 hours at 180C, the solvent is removed and the product is dist;lled in vacuo. It is then subjected to chromatography on silica gel in eth~r and is distilled once more. This gives 5.54 9 (19.9 mmol) of 1-phenyl-2-n-hexylbenzimidazole as a light yellow liqu;d of boiling point 165-168C/0.25 mm Hg, corresponding to a yield of 40X of theory.
Example 115:
The procedure described in Example 113 is repeated, except that 7.91 9 (100 mmol) of hydroxymethylcyclopropane are used in place of n-pentyl alcohol. After 8 hours at 180C, the product is distilled, subjected to chromato-graphy on silica gel in dichloromethane and dist;lled once more in vacuo. This gives 5~2 9 ~Z2~2 mmol) of 1-phenyl-2-cyclopropanylbenzimidazole as a yellow oil of boiling point 146-148C/0.1 mm Hg, corresponding to a yield of 45% of theory.
~ 37~35 Example 116:
The procedure descr;bed in Example 113 is repeated, except that 7.89 ml (100 mmol) of ethylene glycol monomethyl ether are used in place of n-pentyl alcohol. After 8 hours at 180C, the mixture is ~orked up in accordance with Example 113. The product is then recrystallised from 50 ml of n-hexane. This gives 2.8 g (11.8 mmol) of 1 phenyl-2-methoxymethylbenz;midazole as light brown crystals of melt-ing point 70.3C, corresponding to a yield of 24% of theory~
Example 117:
The procedure described in Example 114 is repeated~
except''that 13.0 ml (150 mmol~ of furfuryl alcohol and 0.33 g (3.2 mmol) of l;th;um acetate-dihydrate are used in place of azobenzene and sod;um acetate. After 8 hours at 130, the mixture is distilled as ;n Example 114 and the product ;s recrystall;sed from 100 ml of cyclohexane. Th;s gives 4.3 9 (16.5 mmol) of 1-phenyl-2-(2-furanyl)-benz;midazole as light brown crystals of melt;ng po;nt 12~.9C, corresponding to a y;eld of 33% of theory.
Example 118:
The procedure descr;bed in Example 117 is repeated, except that 15.5 ml (150 mmol) of benzyl alcohol are used in place of furfuryl alcohol. After 8 hours at 180C~ the solvent is removed and the residue is subjected to chromato-graphy on silica gel in ether/d;chloromethane. Two recrys-tall;sat;ons from 100 ml and 150 ml of n hexane give 3.0 g (11.1 mmol) of 1~2-diphenylbenzimidazole as white crystals of melting point 111.7a, corresponding to a yield of 22%
of theory.
Example 119:
30 ml of n-butanol are in;t;ally ;ntroduced ;nto a pressure tube, and carbon monoxide is passed ~hrough. 10.50 g ~50 mmol) of 4,4'-dimethylazobenzene, 4~1 9 (53 mmoi~ of sodium acetate, 0~1308 9 ~0.5 mmol) of ruthenium tr;chloride-tr;hydrate and 0.524 g (2 mmol) of triphenylphosphine are added, and the tube ;s sealed under carbon monox;de at normal pressure. After 8 hours at l~OoC~ the solvent is removed~
~3~79L3~
and the product ;s distilled in vacuo and then recrystallised from 20 ml of n-pentane. This gives 6.6 9 (25 mmol) of 1-(4'-methylphenyl)-2-n-propyl-6-methylbenzimidazole as white crystals of meltin~ point 88.8C, corresponding to a yield of 50~ of theory.
Example 120:
The procedure described in Example 119 is repeated, except that 10.9 g ~50 mmol) of 4,4~-difluoroazobenzene are used in place of dimethylazobenzene~ After 8 hcurs at 180C, the product is distilled as in Example 119 and then recrys-tallised from 30 ml of n-pentane~ This gives 3.71 9 ~13.b mmol) of 1-(4'-fluorophenyl)-2-n-propyl-6-fluorobenzimidazole as yellow crystals of melt;ng point 75.3, correspondlng to a yield of 27% of ~heory.
Example 121:
The procedure described in Example 119 is repeated, except that 12.55 9 t50 mmol) of 4,4'-dichloroazobenzene are used in place of dimethylazobenzene. After 8 hours at 180C, the product is distilled in accordance with Example 11g and subjected to chroma~ography on silica gel in dichloromethane~
After recrystallisation from 50 ml of n-hexane9 this gives 1.2 g t3.9 mmol) of 1-t4'-chlorophenyl)-2-n-propyl-6-chloro benzimidazole as white crystals of melting point 100.2~
corresponding to a yield of ~X of theory.
Example 122:
The procedure described in Example 114 is repeated~
except that 12.55 9 tS0 mmol) of 4,4'-dichloroazobenzene and 11.21 ml ~150 ml) of n-propanol are used in place of azo-benzene and n-heptanol. After 8 hours at 180C and dist;l-lation in accordance with Example 114, the product is recrys~
tallised from a mixture of 100 ml of cyclohexane and 150 ml of n-hexane. This g;ves 4.8 g ~16.5 mmol) of 1 t4'-chloro-phenyl)-2~ethyl-6 chlorobenzimidazole as white crystals of melt;ng point 141.3C, corresponding to a yield of 33% of theory.
Example 123:
The procedure described in Example 114 is repeated, 3L;~37~3~i except that 10.5 9 (50 mmol) of 4,4'-dimethylazobenzene and 11.89 ml (150 mmol) of hydroxymethylcyclopropane are used in place of azobenzene and n-heptanol. After 8 hours at 180C
and distillation in accordance with Example 114, the product is subjected to chromatography on siLica gel in ether and then recrystallised from 50 ml of n-hexaneO This gives ~.02 9 ~23.0 mmol) of 1-(4'-methylphenyl)-2-cyclopropanyl-6-methylbenzimidazole as white crystals of melting point 93.6C, corresponding to a y;eld of 46~ of theory.
Example 124:
.
The procedure described in Example 122 is repeated, except that 9.8 9 (50 mmol) of 4 methylazobenzene are used in place of dichloroazobenzene. After 8 hours at 180C and distillation in accordance with Example 122~ this gives 8.8 g ~37.3 mmol) of a mixture of isomers, which consists of 60%
o~ 1-t4'-methylphenyl)-2-ethylbenzimidazole and 40% of 1-phenyl-2 ethyl-6-methylbenz;midazole, as a yellow Oilf cor~
responding to a total yield of 75% of theoryD
Example 125:
The procedure described in Example 122 is repeated, except that 10.0 g (50 mmol) of 4-fluoroazobenzene are used in place of dichloroazobenzene. After 8 hours at 180C and distillation in accordance with Example 122, this gives 7.9 9 (32.9 mmol) of a mixture of isomers, which consists of 50%
each of 1-~4'-fluorophenyl)-2-ethylbenzimidazole and 1-phenyl-2-ethyl-6-fluorobenzimidazole, as a yellow oil, correspond-ing to a total yield of 66% of theory Example 126~
The procedure described in Example 122 is repeated, except that 10.8 g (50 mmol) of 4-chloroazobenzene are used in place of dichloroazobenzene. After 8 hours at 180C
and distillation in accordance with Example 122~ this gives 3.4 g t1303 mmol) of a mixture of isomers~ wh;ch consists of 53% of 1-~4'-chlorophenyl)-2-ethyl-benzimidazole and 4~ of 1-phenyl-2-ethyl-6-chlorobenzimidazole, as a yellow oil, corresponding to a total yiPld of 27% of theoryO
- 27 - ~ ~37435 Example 127:
The procedure described in Example 122 is repeated, except that 13.05 9 (50 mmol) of 4-bromoazobenzene are used in place of dichloroazobenzene. After ~ hours at 180C and distillation in accordance with Example 122, this gives 3.1 9 (10.3 mmol) of a mixture of isomers, which consists of 43% of 1-(4'-bromophenyl)-2~ethylbenzimidazole and 57% of 1-phenyl-2-ethyl-o-bromobenzimidazole, as a yellow oil~
corresponding to a total yield of 21%~
Example 128:
The procedure described in Example 11~ is repeated, except that 6.0 g (26 mmol) of 3,5,3'-trimethyla~obenzene,
5.83 ml (78 mmol) of n-propanol, 0.0639 g (û.7~ ~mol) of sodium acetate, 0.068 9 ~0.26 mmol) of ruthen;um tr;chloride-trihydrate~ 0.272 9 (1.04 mmol) of triphenylphosphine and 13 ml of te~ramethylurea are used. After 8 hours at 180C
and distillation in accordance with Example 114, the product is recrystallised from 50 ml of hexane. This gives 2.6 g (9~8 mmol) of a mixture of isomers, which consists of 54% of 1-t4'-methylphenyl)-2-ethyl-5,7-dimethylbenzimidazole and 46% of 1-(3',5'-dimethylphenyl)-2-ethyl-6-methylbenzimidazoLe, as white crystals, corresponding to a total yield of 20% of theory.
Example 1290 The procedure described in Example 122 is repeated, except that 12.1 g (50 mmol) of 3~3'-dime~hoxyazobenzene are used in place of dichloroazobenzene~ After 8 hours at 180C and distillation in accordance with Example 122, the product ;s subjected to chromatography on silica gel ;n d;-chloromethane/ether and once more distîlled in vacuo. This gives 5.4 g (19~1 mmol) of a mixture of isomers, ~hich con-sists of 56% of 1-(3'-methoxyphenyl)-2-ethyl-5-methoxybenz-imidozole and 44% of 1-(3'-methoxyphenyl3~2-ethyl-7-methoxy-benzimidazole, as a yellow oil~ corresponding to a total y;eld of 38% of theory.
Example 130:
The procedure described in Example 122 is repeated~
~3~3S
except that 10.5 9 (50 mmol) of 3,3'-dimethylazobenzene are used in place of dichloroazobenzene. After 8 hours at 180C
and d;stillation in accordance with Example 122, the product is subjected to chromatography on s;lica gel in dichloro-methane/ether and distilled once more. This gives 5~9 9 (23.6 mmol) of a mixture of isomers, which consists of 52%
of 1-t3'-methylphenyl)-2-ethyl-5 methylbenzimidazole and 48X
of 1-(3'-methylphenyl) 2-ethyl-7-methylbenzimidazole~ as a yellow oil, corresponding to a total yield of 47X of theory.
Example 131:
The procedure described ;n Example 122 is repeated, except that 12.55 g tS0 mmol) of 3,3'-dichloroazobenzene are used ;n place of 4,4'-dichloroazobenzene. After 8 hours at 180C and d;stillation in accordance with Example 122, this gives 1.8 9 (6.2 mmol) of a 0ixture of isomers~ which consists of SOX each of 1-t3'-chlorophenyl)-2-ethyl-5-chloro-benzimidazole and 1-t3'-chlorophenyl)-2-ethyl-7-chlorobenz-imidazole, as a yellow o;l, correspondin~ to a total yield of 12% of theory.
Example 132:
The procedure described in Example 114 is repeated, except that 10.5 9 (50 mmol) of 4,4'-dimethylazobenzene and 13.2 ml (150 mmol) of isopentyl alcohol are used in place of azobenzene and n-heptanolO After 8 hours at 180C and distillation in accordance ~ith Example 114, the product is recrystallised from 50 ml of n-pentane. This gives 7~7 g (27.7 mmol) of 1-(4'-methylphenyl~-2-isopropylmethyl-~-methylbenzimidazole as yellow crystals of melting point 65.3C, corresponding to a yield of 5S% of theory.
Example 133:
The procedure described in Example 114 is repeatedr except that 10.5 9 t50 mmol) of 4~4'-dimethylazobenzene and 16.96 ml tl50 mmol) of 2-hydroxymethyltetrahydropyran are used in place of azobenzene and n-heptanol. After 8 hours at 180C and dist;llation ;n accordance with Exanple 114, the product ;s recrystallised from 250 ml of n hexane. This g;ves 4.8 9 (15.7 mmol) of 1-t4/-methylphenyl)~2--(2 tetra-~237~35 hydropyranyl)-6-methylbenzimidazole as white crystals of melting point 134.7C, corresponding to a yield of 33% of theory~
Example 134:
The procedure described in Example 113 is repeated, except that 11.66 ml (100 mmol~ of ethyl L-lactate are used in pLace of n-pentyl alcohol. A-fter 8 hours at 180C and distillation in accordance with Example 113, the product is distilled once more in vacuo. This gives 3.3 g t15.9 mmol) of 1-phenyl-2-methylbenzimidazole as a`yellow oil of boiling point 140C/0.1 mm Hg, corresponding to a yield oF 32% of theory.
Example 135:
The procedure described in Example 113 is repeated, except that 9.78 ml (100 mmol) of ethyl acetate are used in place of n-pentyl alcohol. After 8 hours at 180C, the product is distilled in accordance with Example 113. This gives 4.5 9 (21.6 mmol~ of 1-phenyl-2-methylbenzimidazole as a yellow oil, correspond;ng to a y;eld of 43X of theory.
Example 136:
The procedure described in Example 110 is repeated, except that 0.1905 9 tO.25 mmol) of trichloro-bis-(triphenyl-phosphine)-nitrosylruthen;umtII) is used in place of ruthen-ium tr;chloride-tr;hydrate and tr;phenylphosph;ne. After 8 hours at 180C and workin~-up in accordance with Example 113, th;s g;ves, after d;stillation, 1.26 9 tS.3 mmol) of 1-phenyl-2-n-propylbenz;m;dazole as a yellow ilr corres-pond;ng to a y;eld of 21X of theory.
Example 137:
The procedure descr;bed ;n Example 114 is repeated, except that 12.1 ml t150 mmol~ of ethyl formate are used in place of n-heptanol. After 8 hours at 180C and distilla-tion ;n accordance w;th Example 114, th;s gives 2.45 9 (11.8 mmol) of 1-phenyl-2-methylbenzim;dazole as a yellow o;l, correspond;ng to a y;eld of 23% of theory.
Example 138:
The procedure descr;bed in Example 21 is repeated, ~3~
except that ~.0329 9 (0.1Z5 mmol) cf ruthenium trichloride-trihydrate and 0.03295 9 tO.125 mmol) of rhodium trichloride-trihydrate are used in place of ruthenium trichloride-tri-hydrate. After 8 hours under reflux conditions, the soLvent is removed and the product is distilled in vacuo. rhis gives 3n35 9 (14.2 mmol) of 1-phenyl-2-n-propylbenzimidazole as a yellow oil of boiling point 133-135C/0~1 mm Hg~ cor-responding to a yield of 57% of theorya Example 139:
The procedure described in Example 21 is repeated, except that 12.5 ml of N,N-dimethylacetamide and 0.06~ 9 (0.25 mmol) of rhodium tr;chloride-trihydrate are used in place of tetramethylurea and ruthenium trichloride-trihydra~e.
After 8 hours under reflux conditions (164-165C), this gives 1.0 g (~2 mmol) of 1-phenyl-2-n-propylbenzimidazole, corresponding to a yield of 17% of theory.
Example 140 .
The procedure described ;n Example SO is repeated, except that the batch size is doubled and 0.1318 9 (0.5 mmol) of rhodium trichloride-trihydrate is used in place of ruthen-ium trichloride-trihydrate. After 21 hours under reflux conditions (179-180C) and working-up in accordance ~ith Example SO, this gives 0.72 9 (2.~ mmol) of 1-4'-chlorophenyl)-2-n propyl-6-chLorobenzimidazole, corresponding to a yield of 5% of theory.
Example 141-The procedure described in Example 110 is repeated,except that 4.6 9 t25 mmol) of 2-methylazobenzene are used in place of azobenzene. After 8 hours at 180C, the mix-ture is distilled and the crude product is subjected to chromatography on silica gel in dichloromethane. ~fter re-moval of the solvent, the product is distilled once more~
This gives 1.62 9 ~6~5 mmol) of a mixture of isomers, which consists of 50X each o~ 1-phenyl-2-n-propyl-4-methylben~imid-azole and 1-~2'-methylphenyl)~2~-n-propylbenzimidazole, as a yellow oil, corresponding to a yield of 26% of theory.
- 31 ~237435 Example 14Z:
The procedure described in Example 114 i3 repeated, except that 10.0 9 (50 mmol) of 2-fluoroazobenzene and 13.72 ml (150 mmol) of n-butanol are used in place of azo-benzene and n-heptanol. After 8 hours at 180C and working-up in accordance with Example 141, this gives 3.36 9 (13.2 mmol) of a mixture of isomers, which consists of 31% of 1-phenyl-2-n-propyl-4-fluorobenzimidazole and 69X of 1-t2'-fluorophenyl)-Z-n-propylbenzimidazole, corresponding to a yield of 26X of theory.
Example 143:
The procedure described in Example 142 ;s repeated, except that 10.5 g (50 mmol) of 2,2'-dimethylazobenzene are used ;n place of 2-fluoroazobenzene. After 8 hours at 180C
and work;ng-up ;n accordance with Example 141~ th;s gives
and distillation in accordance with Example 114, the product is recrystallised from 50 ml of hexane. This gives 2.6 g (9~8 mmol) of a mixture of isomers, which consists of 54% of 1-t4'-methylphenyl)-2-ethyl-5,7-dimethylbenzimidazole and 46% of 1-(3',5'-dimethylphenyl)-2-ethyl-6-methylbenzimidazoLe, as white crystals, corresponding to a total yield of 20% of theory.
Example 1290 The procedure described in Example 122 is repeated, except that 12.1 g (50 mmol) of 3~3'-dime~hoxyazobenzene are used in place of dichloroazobenzene~ After 8 hours at 180C and distillation in accordance with Example 122, the product ;s subjected to chromatography on silica gel ;n d;-chloromethane/ether and once more distîlled in vacuo. This gives 5.4 g (19~1 mmol) of a mixture of isomers, ~hich con-sists of 56% of 1-(3'-methoxyphenyl)-2-ethyl-5-methoxybenz-imidozole and 44% of 1-(3'-methoxyphenyl3~2-ethyl-7-methoxy-benzimidazole, as a yellow oil~ corresponding to a total y;eld of 38% of theory.
Example 130:
The procedure described in Example 122 is repeated~
~3~3S
except that 10.5 9 (50 mmol) of 3,3'-dimethylazobenzene are used in place of dichloroazobenzene. After 8 hours at 180C
and d;stillation in accordance with Example 122, the product is subjected to chromatography on s;lica gel in dichloro-methane/ether and distilled once more. This gives 5~9 9 (23.6 mmol) of a mixture of isomers, which consists of 52%
of 1-t3'-methylphenyl)-2-ethyl-5 methylbenzimidazole and 48X
of 1-(3'-methylphenyl) 2-ethyl-7-methylbenzimidazole~ as a yellow oil, corresponding to a total yield of 47X of theory.
Example 131:
The procedure described ;n Example 122 is repeated, except that 12.55 g tS0 mmol) of 3,3'-dichloroazobenzene are used ;n place of 4,4'-dichloroazobenzene. After 8 hours at 180C and d;stillation in accordance with Example 122, this gives 1.8 9 (6.2 mmol) of a 0ixture of isomers~ which consists of SOX each of 1-t3'-chlorophenyl)-2-ethyl-5-chloro-benzimidazole and 1-t3'-chlorophenyl)-2-ethyl-7-chlorobenz-imidazole, as a yellow o;l, correspondin~ to a total yield of 12% of theory.
Example 132:
The procedure described in Example 114 is repeated, except that 10.5 9 (50 mmol) of 4,4'-dimethylazobenzene and 13.2 ml (150 mmol) of isopentyl alcohol are used in place of azobenzene and n-heptanolO After 8 hours at 180C and distillation in accordance ~ith Example 114, the product is recrystallised from 50 ml of n-pentane. This gives 7~7 g (27.7 mmol) of 1-(4'-methylphenyl~-2-isopropylmethyl-~-methylbenzimidazole as yellow crystals of melting point 65.3C, corresponding to a yield of 5S% of theory.
Example 133:
The procedure described in Example 114 is repeatedr except that 10.5 9 t50 mmol) of 4~4'-dimethylazobenzene and 16.96 ml tl50 mmol) of 2-hydroxymethyltetrahydropyran are used in place of azobenzene and n-heptanol. After 8 hours at 180C and dist;llation ;n accordance with Exanple 114, the product ;s recrystallised from 250 ml of n hexane. This g;ves 4.8 9 (15.7 mmol) of 1-t4/-methylphenyl)~2--(2 tetra-~237~35 hydropyranyl)-6-methylbenzimidazole as white crystals of melting point 134.7C, corresponding to a yield of 33% of theory~
Example 134:
The procedure described in Example 113 is repeated, except that 11.66 ml (100 mmol~ of ethyl L-lactate are used in pLace of n-pentyl alcohol. A-fter 8 hours at 180C and distillation in accordance with Example 113, the product is distilled once more in vacuo. This gives 3.3 g t15.9 mmol) of 1-phenyl-2-methylbenzimidazole as a`yellow oil of boiling point 140C/0.1 mm Hg, corresponding to a yield oF 32% of theory.
Example 135:
The procedure described in Example 113 is repeated, except that 9.78 ml (100 mmol) of ethyl acetate are used in place of n-pentyl alcohol. After 8 hours at 180C, the product is distilled in accordance with Example 113. This gives 4.5 9 (21.6 mmol~ of 1-phenyl-2-methylbenzimidazole as a yellow oil, correspond;ng to a y;eld of 43X of theory.
Example 136:
The procedure described in Example 110 is repeated, except that 0.1905 9 tO.25 mmol) of trichloro-bis-(triphenyl-phosphine)-nitrosylruthen;umtII) is used in place of ruthen-ium tr;chloride-tr;hydrate and tr;phenylphosph;ne. After 8 hours at 180C and workin~-up in accordance with Example 113, th;s g;ves, after d;stillation, 1.26 9 tS.3 mmol) of 1-phenyl-2-n-propylbenz;m;dazole as a yellow ilr corres-pond;ng to a y;eld of 21X of theory.
Example 137:
The procedure descr;bed ;n Example 114 is repeated, except that 12.1 ml t150 mmol~ of ethyl formate are used in place of n-heptanol. After 8 hours at 180C and distilla-tion ;n accordance w;th Example 114, th;s gives 2.45 9 (11.8 mmol) of 1-phenyl-2-methylbenzim;dazole as a yellow o;l, correspond;ng to a y;eld of 23% of theory.
Example 138:
The procedure descr;bed in Example 21 is repeated, ~3~
except that ~.0329 9 (0.1Z5 mmol) cf ruthenium trichloride-trihydrate and 0.03295 9 tO.125 mmol) of rhodium trichloride-trihydrate are used in place of ruthenium trichloride-tri-hydrate. After 8 hours under reflux conditions, the soLvent is removed and the product is distilled in vacuo. rhis gives 3n35 9 (14.2 mmol) of 1-phenyl-2-n-propylbenzimidazole as a yellow oil of boiling point 133-135C/0~1 mm Hg~ cor-responding to a yield of 57% of theorya Example 139:
The procedure described in Example 21 is repeated, except that 12.5 ml of N,N-dimethylacetamide and 0.06~ 9 (0.25 mmol) of rhodium tr;chloride-trihydrate are used in place of tetramethylurea and ruthenium trichloride-trihydra~e.
After 8 hours under reflux conditions (164-165C), this gives 1.0 g (~2 mmol) of 1-phenyl-2-n-propylbenzimidazole, corresponding to a yield of 17% of theory.
Example 140 .
The procedure described ;n Example SO is repeated, except that the batch size is doubled and 0.1318 9 (0.5 mmol) of rhodium trichloride-trihydrate is used in place of ruthen-ium trichloride-trihydrate. After 21 hours under reflux conditions (179-180C) and working-up in accordance ~ith Example SO, this gives 0.72 9 (2.~ mmol) of 1-4'-chlorophenyl)-2-n propyl-6-chLorobenzimidazole, corresponding to a yield of 5% of theory.
Example 141-The procedure described in Example 110 is repeated,except that 4.6 9 t25 mmol) of 2-methylazobenzene are used in place of azobenzene. After 8 hours at 180C, the mix-ture is distilled and the crude product is subjected to chromatography on silica gel in dichloromethane. ~fter re-moval of the solvent, the product is distilled once more~
This gives 1.62 9 ~6~5 mmol) of a mixture of isomers, which consists of 50X each o~ 1-phenyl-2-n-propyl-4-methylben~imid-azole and 1-~2'-methylphenyl)~2~-n-propylbenzimidazole, as a yellow oil, corresponding to a yield of 26% of theory.
- 31 ~237435 Example 14Z:
The procedure described in Example 114 i3 repeated, except that 10.0 9 (50 mmol) of 2-fluoroazobenzene and 13.72 ml (150 mmol) of n-butanol are used in place of azo-benzene and n-heptanol. After 8 hours at 180C and working-up in accordance with Example 141, this gives 3.36 9 (13.2 mmol) of a mixture of isomers, which consists of 31% of 1-phenyl-2-n-propyl-4-fluorobenzimidazole and 69X of 1-t2'-fluorophenyl)-Z-n-propylbenzimidazole, corresponding to a yield of 26X of theory.
Example 143:
The procedure described in Example 142 ;s repeated, except that 10.5 g (50 mmol) of 2,2'-dimethylazobenzene are used ;n place of 2-fluoroazobenzene. After 8 hours at 180C
and work;ng-up ;n accordance with Example 141~ th;s gives
6.72 9 (Z6.9 mmol) of 1-t2'-methylphenyl)-2-n-propyl-4-methylbenz;midaYole as a yellow oil of bo;l;ng po;nt 133-135C/0~1 mm Hg, correspond;ng to a yield of 54~ of theory.
Claims (10)
1. A process for the preparation of benzimidazoles of the formula (I), in which R is an aliphatic or aromatic hydrocarbon radical or heterocyclic radical, containing 4 to 8 ring atoms and one or two identical or different heteroatoms, which are unsubstituted or substituted by C1-C6-alkyl, C1-C6-alkoxy, C1-C6-alkylthio, cycloalkyl having 3 to 7 ring carbon atoms, phenyl, naphthyl, halogen, hydroxyl, nitrile or amino, and R1, R2, R3, R4, R5, R6, R9 and R10 independently of one an-other are a hydrogen atom, halogen, carboxylate, alkyl, alkoxy, alkylthio, alkoxyalkyl, cycloalkyl, aryl oraralkyl, or two adjacent groups out of R1, R2, R3 and R9, or R4, R5, R6 and R10 in each case represent -CH=CH-CH=CH- which com-prises reacting an azobenzene of the formula (II) in which R1 to R6 as well as R9 and R10 are as defined above, in the presence of a ruthenium or rhodium catalyst or mixtures of such catalysts and at temperatures of at least 120°C with a tertiary amine containing at least one R-CH2-group or, in the presence of a ruthenium catalyst, with a primary alcohol or acid ester thereof, of the formula R - CH2 - O - A (III) in which R is as defined above and A is a hydrogen atom or an aliphatic acyl radical, which is unsubstituted or substi-tuted by phenyl, halogen, OH, SH or carboxyl.
2. A process according to claim 1, wherein a hydrocarbon radical R is alkyl, alkenyl, alkynyl, cycloalkyl, cyclo-alkenyl or aryl, or a heterocyclic radical R contains a total of 4 to 8 ring atoms and one or two hetero-atoms, said radicals being unsubstituted or substituted as defined in claim 1.
3. A process according to claim 1, wherein an aliphatic acyl radical A contains 1 to 8 C atoms.
4. A process according to claim 1, wherein the azo-benzene of the formula II in the reaction mixture is replaced by an N-phenyl-ortho-phenylenediamine.
5. A process according to claim 1, wherein the tertiary amine is of the formula (IV) in which R is as defined in claim 1 and R7 and R8 indepen-dently of one another are methyl, .alpha. -branched alkyl, cyclo-alkyl, aryl or .alpha. -branched aralkyl, or R7 and R8 together are trimethylene, tetramethylene or 3-oxapentylene, or R7 and R8 are identical or different R-CH2- groups.
6. h process according to claim 1, wherein ruthenium-or rhodium trichloride trihydrate are used as the catalyst.
7. A process according to claim 1, wherein the ruthen-ium and/or rhodium catalyst is employed in a quantity of 00001-20 mol % relative to the azobenzene of the formula II.
8. A process according to claim 1, wherein additionally a basic compound is added if reactants of the formula III are used.
9. A process according to claim 8, wherein the basic compound is a tertiary amine or an alkali metal salt or alkaline earth metal salt of a carboxylic acid.
10. A process according to claim 9, wherein the basic compound is employed in a quantity of 0.1 to 60 mol %, relative to the azobenzene of the formula II.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH4421/83-4 | 1983-08-12 | ||
| CH442183 | 1983-08-12 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1237435A true CA1237435A (en) | 1988-05-31 |
Family
ID=4275824
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000460703A Expired CA1237435A (en) | 1983-08-12 | 1984-08-10 | Process for the preparation of substituted benzimidazoles |
Country Status (4)
| Country | Link |
|---|---|
| EP (1) | EP0138750B1 (en) |
| JP (1) | JPS6058966A (en) |
| CA (1) | CA1237435A (en) |
| DE (1) | DE3465990D1 (en) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2673943B1 (en) * | 1991-03-13 | 1994-02-18 | Roussel Uclaf | NEW IMIDAZOLE DERIVATIVES, THEIR PREPARATION PROCESS, THE NEW INTERMEDIATES OBTAINED, THEIR APPLICATION AS MEDICAMENTS AND THE PHARMACEUTICAL COMPOSITIONS CONTAINING THEM. |
| AU653524B2 (en) * | 1990-06-08 | 1994-10-06 | Roussel-Uclaf | New imidazole derivatives, their preparation process, the new intermediates obtained, their use as medicaments and the pharmaceutical compositions containing them |
| FR2663027B1 (en) * | 1990-06-08 | 1994-12-02 | Roussel Uclaf | NEW IMIDAZOLE DERIVATIVES, THEIR PREPARATION PROCESS, THE NEW INTERMEDIATES OBTAINED, THEIR APPLICATION AS MEDICAMENTS AND THE PHARMACEUTICAL COMPOSITIONS CONTAINING THEM. |
| CN1784388B (en) * | 2003-03-13 | 2012-02-22 | 出光兴产株式会社 | Nitrogen-containing heterocyclic derivative and organic electroluminescent element using same |
| US8036710B2 (en) * | 2004-05-07 | 2011-10-11 | Qualcomm, Incorporated | Power-efficient multi-antenna wireless device |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH478526A (en) * | 1964-08-07 | 1969-09-30 | Merck & Co Inc | Use of benzimidazoles as fungicides |
-
1984
- 1984-08-06 EP EP19840810387 patent/EP0138750B1/en not_active Expired
- 1984-08-06 DE DE8484810387T patent/DE3465990D1/en not_active Expired
- 1984-08-09 JP JP16576384A patent/JPS6058966A/en active Pending
- 1984-08-10 CA CA000460703A patent/CA1237435A/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| EP0138750B1 (en) | 1987-09-09 |
| DE3465990D1 (en) | 1987-10-15 |
| JPS6058966A (en) | 1985-04-05 |
| EP0138750A1 (en) | 1985-04-24 |
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