CA1154023A - Process for preparing imidazole derivative - Google Patents
Process for preparing imidazole derivativeInfo
- Publication number
- CA1154023A CA1154023A CA000368285A CA368285A CA1154023A CA 1154023 A CA1154023 A CA 1154023A CA 000368285 A CA000368285 A CA 000368285A CA 368285 A CA368285 A CA 368285A CA 1154023 A CA1154023 A CA 1154023A
- Authority
- CA
- Canada
- Prior art keywords
- formula
- thiomethyl
- quaternary
- preparing
- methyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 7
- 150000002460 imidazoles Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 11
- 125000005843 halogen group Chemical group 0.000 claims abstract description 5
- 150000003839 salts Chemical class 0.000 claims abstract description 5
- 239000002253 acid Substances 0.000 claims abstract description 4
- 150000004714 phosphonium salts Chemical group 0.000 claims abstract description 4
- 125000001453 quaternary ammonium group Chemical group 0.000 claims abstract description 4
- 239000007864 aqueous solution Substances 0.000 claims abstract description 3
- 239000002585 base Substances 0.000 claims abstract description 3
- 125000001246 bromo group Chemical group Br* 0.000 claims abstract description 3
- 125000001309 chloro group Chemical group Cl* 0.000 claims abstract description 3
- 239000012074 organic phase Substances 0.000 claims abstract description 3
- 239000003444 phase transfer catalyst Substances 0.000 claims abstract description 3
- JEOZNMMOIBLWLV-UHFFFAOYSA-N 2-[(5-methyl-1h-imidazol-4-yl)methylsulfanyl]ethanamine Chemical compound CC=1N=CNC=1CSCCN JEOZNMMOIBLWLV-UHFFFAOYSA-N 0.000 claims abstract 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical group [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract 2
- 229910052783 alkali metal Chemical group 0.000 claims abstract 2
- 150000001340 alkali metals Chemical group 0.000 claims abstract 2
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract 2
- 239000001257 hydrogen Substances 0.000 claims abstract 2
- 238000000034 method Methods 0.000 claims description 10
- HTZCNXWZYVXIMZ-UHFFFAOYSA-M benzyl(triethyl)azanium;chloride Chemical compound [Cl-].CC[N+](CC)(CC)CC1=CC=CC=C1 HTZCNXWZYVXIMZ-UHFFFAOYSA-M 0.000 claims description 9
- 238000006243 chemical reaction Methods 0.000 claims description 9
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 6
- 239000000243 solution Substances 0.000 claims description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 4
- XKBGEWXEAPTVCK-UHFFFAOYSA-M methyltrioctylammonium chloride Chemical compound [Cl-].CCCCCCCC[N+](C)(CCCCCCCC)CCCCCCCC XKBGEWXEAPTVCK-UHFFFAOYSA-M 0.000 claims description 4
- 150000001298 alcohols Chemical class 0.000 claims description 2
- 239000003960 organic solvent Substances 0.000 claims description 2
- RYVBINGWVJJDPU-UHFFFAOYSA-M tributyl(hexadecyl)phosphanium;bromide Chemical compound [Br-].CCCCCCCCCCCCCCCC[P+](CCCC)(CCCC)CCCC RYVBINGWVJJDPU-UHFFFAOYSA-M 0.000 claims description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 description 5
- 125000000066 S-methyl group Chemical group [H]C([H])([H])S* 0.000 description 4
- RAXXELZNTBOGNW-UHFFFAOYSA-N 1H-imidazole Chemical class C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- VKPPFDPXZWFDFA-UHFFFAOYSA-N 2-chloroethanamine Chemical compound NCCCl VKPPFDPXZWFDFA-UHFFFAOYSA-N 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- UFULAYFCSOUIOV-UHFFFAOYSA-N cysteamine Chemical compound NCCS UFULAYFCSOUIOV-UHFFFAOYSA-N 0.000 description 3
- 229960003151 mercaptamine Drugs 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- -1 5-methyl-4-imidazolyl Chemical group 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- AXJZCJSXNZZMDU-UHFFFAOYSA-N (5-methyl-1h-imidazol-4-yl)methanol Chemical group CC=1N=CNC=1CO AXJZCJSXNZZMDU-UHFFFAOYSA-N 0.000 description 1
- ZOHLKTFCEUOOOQ-UHFFFAOYSA-N 4-(methoxymethyl)-5-methyl-1h-imidazole Chemical compound COCC=1N=CNC=1C ZOHLKTFCEUOOOQ-UHFFFAOYSA-N 0.000 description 1
- MLLYSQGRMFTIIZ-UHFFFAOYSA-N 5-(methylsulfanylmethyl)-1h-imidazole Chemical compound CSCC1=CN=CN1 MLLYSQGRMFTIIZ-UHFFFAOYSA-N 0.000 description 1
- 102000003710 Histamine H2 Receptors Human genes 0.000 description 1
- 108090000050 Histamine H2 Receptors Proteins 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- 238000005903 acid hydrolysis reaction Methods 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- USFRYJRPHFMVBZ-UHFFFAOYSA-M benzyl(triphenyl)phosphanium;chloride Chemical compound [Cl-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(C=1C=CC=CC=1)CC1=CC=CC=C1 USFRYJRPHFMVBZ-UHFFFAOYSA-M 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 238000006698 hydrazinolysis reaction Methods 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 125000005543 phthalimide group Chemical group 0.000 description 1
- 239000003495 polar organic solvent Substances 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- HYHCSLBZRBJJCH-UHFFFAOYSA-M sodium hydrosulfide Chemical compound [Na+].[SH-] HYHCSLBZRBJJCH-UHFFFAOYSA-M 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 230000003407 synthetizing effect Effects 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- NNENFOSYDBTCBO-UHFFFAOYSA-M tributyl(hexadecyl)phosphanium;chloride Chemical compound [Cl-].CCCCCCCCCCCCCCCC[P+](CCCC)(CCCC)CCCC NNENFOSYDBTCBO-UHFFFAOYSA-M 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/64—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Catalysts (AREA)
Abstract
Abstract of the Disclosure The present invention relates to a novel process for preparing 4-[(2-aminoethyl)thiomethyl]-5-methyl imidazole of the formula I
and its acid addition salts, characterized as a process for preparing 4-[(2-aminoethyl)thiomethyl]-5-methyl imidazole of the formula and its acid addition salts, characterized in that a compound of the formula
and its acid addition salts, characterized as a process for preparing 4-[(2-aminoethyl)thiomethyl]-5-methyl imidazole of the formula and its acid addition salts, characterized in that a compound of the formula
Description
~540~
A PROCESS FOR PREPARING IMIDAZOLE DERIVATIVE
The present invention relates to a novel process for preparing 4- ~(2-aminoethyl)thiomethyl~-5-methyl imidazole of the formula 3 ¦ - ~ CH2SC~2CH2NH2 HN
and its acid addition salts~
4-~(2-aminoethyl)thiomethyl~-5-methyl imidazole is an important intermediate in the preparation of pharmacologically active com-pounds, such as N-cyano-N'-me~hyl-N"-~2-[(5-methyl-4-imidazolyl)-methylthio]ethyl3-guanidine, which acts as an active histamine antagonist on H2 receptors and is known under the generic name of "cimetidin". The intermediate and processes for the preparation thereof were disclo.sed and described for the first time in the British patent 1,338,169.
The known and described processes arelbased on the reaction of 4-halomethyl-, 4-hydroxymethyl- or 4-methoxymethyl-5-methyl imidazole or its hydrohalide of the ormula CH3 ~ _ I CH2Q
H ~ N
wherein Q represents a halogen, a hydroxy of a methoxy group, with cysteamine or its hydrohalogenide.
,~
l~S9~ 3 When Q represents a halogen, the reaction is carried out in a basic medium, e.g. in the prssence of sodium ethoxyde or sodium hydroxydeO
Since cysteamine is a primary amine, it is necessary to protect the amino group, ~.g. with a phthalimide group, which is removed after completion of the reaction by acid hydrolysis or hydrazinoly-sis. When Q represents a hydroxy or a methoxy group, the reaction is carried out in an acidic medium in the presence of a 48~ aqueous HBr solution or in glacial acetic acid. The yields of these re-actions are between 70 and 90 ~, the reaction times from 10 to 18 hours and the reaction temperature from 100 to 120C.
The aim of the present invention is to provide a process for pre-paring 4-~(2-aminoethyl)thiomethyl~-5-methyl imidazole with high yields, short reaction times and at room temperature, which would make it possible that the final product I is isolated easily and with high purity.
The aim is achieved by selective alkylation of 4(5)-thiomethyl-5(4)-me~hyl imidazole of the formula CH3 1- ¦ 2 H
HN ~ ~ N
with a 2-haloethylamine, wherein halo means chloro or bromo, at room temperature in a system consisting of a 50 % aqueous solution of a strong base and an organic phase using quaternary ammonium or quaternary phosphonium salts as phase transfer catalysts. As catalysts there can be used e.g. methyltricaprylyl ammonium chloride, benzyltriethyl ammonium chloride, benzyltriphenyl phosphonium chloride, hexadecyltributyl phosphonium bromide etc.
A PROCESS FOR PREPARING IMIDAZOLE DERIVATIVE
The present invention relates to a novel process for preparing 4- ~(2-aminoethyl)thiomethyl~-5-methyl imidazole of the formula 3 ¦ - ~ CH2SC~2CH2NH2 HN
and its acid addition salts~
4-~(2-aminoethyl)thiomethyl~-5-methyl imidazole is an important intermediate in the preparation of pharmacologically active com-pounds, such as N-cyano-N'-me~hyl-N"-~2-[(5-methyl-4-imidazolyl)-methylthio]ethyl3-guanidine, which acts as an active histamine antagonist on H2 receptors and is known under the generic name of "cimetidin". The intermediate and processes for the preparation thereof were disclo.sed and described for the first time in the British patent 1,338,169.
The known and described processes arelbased on the reaction of 4-halomethyl-, 4-hydroxymethyl- or 4-methoxymethyl-5-methyl imidazole or its hydrohalide of the ormula CH3 ~ _ I CH2Q
H ~ N
wherein Q represents a halogen, a hydroxy of a methoxy group, with cysteamine or its hydrohalogenide.
,~
l~S9~ 3 When Q represents a halogen, the reaction is carried out in a basic medium, e.g. in the prssence of sodium ethoxyde or sodium hydroxydeO
Since cysteamine is a primary amine, it is necessary to protect the amino group, ~.g. with a phthalimide group, which is removed after completion of the reaction by acid hydrolysis or hydrazinoly-sis. When Q represents a hydroxy or a methoxy group, the reaction is carried out in an acidic medium in the presence of a 48~ aqueous HBr solution or in glacial acetic acid. The yields of these re-actions are between 70 and 90 ~, the reaction times from 10 to 18 hours and the reaction temperature from 100 to 120C.
The aim of the present invention is to provide a process for pre-paring 4-~(2-aminoethyl)thiomethyl~-5-methyl imidazole with high yields, short reaction times and at room temperature, which would make it possible that the final product I is isolated easily and with high purity.
The aim is achieved by selective alkylation of 4(5)-thiomethyl-5(4)-me~hyl imidazole of the formula CH3 1- ¦ 2 H
HN ~ ~ N
with a 2-haloethylamine, wherein halo means chloro or bromo, at room temperature in a system consisting of a 50 % aqueous solution of a strong base and an organic phase using quaternary ammonium or quaternary phosphonium salts as phase transfer catalysts. As catalysts there can be used e.g. methyltricaprylyl ammonium chloride, benzyltriethyl ammonium chloride, benzyltriphenyl phosphonium chloride, hexadecyltributyl phosphonium bromide etc.
2 -i ~i54()2;~
Another advantage of the process of the invention over knownprocesses for synthetizing 4-[(2-aminoethyl)-thiomethyl~-5-methyl imidazole i5 that the use of cysteamine hydrohalide is avoided.
Instead of this expensive chemical, a 2-haloethylamine, preferably 2-chloroethylamine, which is a cheaper and readily available com-pound, is used. Furthermore, there is no need for a preliminary protection of the amino group in this compound.
As organic solvents there can be used polar organic solvents in which the starting reactant is soluble, such as lower alcohols, acetonitrile and the like. The yields of the final compound of the formula I are extraordinarily high and amount to 85 to 90 % of the theoretical yield.
The starting 4(5?-thiomethyl-5(4)-methyl imidazole and the process-es for preparing the same are disclosed in our Belgian patent 875 845.
Since thiols are not very stable compounds, the reactions are preferably carried out in an inert atmosphere.
In an alternative method an alkali mercaptide of 5(4)-methyl-4(5)-thiomethyl imidazole, which is a stable compound, is used as the starting substance. The reaction conditions are similar to those of the previous case.
The invention is illustrated but not limited by the following Examples.
Example 1 S-methyl-4-thiomethyl imidazole (6.4 g, 0.05 mole) is dissolved in t`-~
. ' ',' 1154(;~
ethanol (80 ml). Thereto a 50 % aqueous NaOH solution (10 ml) is added, followed by the addition of hexadecyltributyl phosphonium chloride (1.16 g, 0.0025 mole) and stirring for 10 minutes in an inert atmosphere at room temperature. Over a period of 15 minutes, a solution of 2-chloroethylamine (4.0 g) in ethanol (30 ml) is added and the resùlting mixture is stirred for 30 minutes at room temperature and then for 30 more minutes at 50C. The solvent is removed by evaporation and the residue is extracted with isopropan-ol.
The inorganic salts are filtered off and hydrogen chloride is pass-ed into the isopropanolic solution until pH 1 is reached.
The reaction mixture is evaporated to dryness and the residue is recrystallized from ethanol. There is obtained 3-C(2-aminoethyl) thiomethyl]-5-methyl imidaæole (10.9 g, 89.3 %) in the form of its dihydrochloride, mnp. 189-191C.
ExamPle 2 The procedure of the previous Example is followed, using, however, benzyltriethyl ammonium chloride (TEBA, 580 mg, 2.5 mmole) as the catalyst. There are obtained 10.8 g (88 %) of the desired com-pound.
Example 3 The procedure of Example 1 is followed, using, however, tricaprylyl-methyl ammonium chloride (Aliquat 336, 1.04 g, 2.5 mmole) as the catalyst. There are obtained 10.9 g (89.3 %) of the desired compound.
~1~46) '~
5-methyl-4-thiomethyl imidazole (1.5 g, 0.01 mole) in ~he form of its sodium mercaptide is dissolved in water (20 ml). Thereto benzyltriethyl ammonium chloride (70 mg, 0.3 mmole) is added. The resulting solution is stirred for 10 minutes at room temperature.
Over a period of 10 minutes 2-chloroethylamine (8.0 g) in ethanol (8 ml) is added dropwise to the reaction mixture. The reaction mixture is stirred for 1.5 hours at room temperature, evaporated to dryness and the rest of the procedure of Example 1 is followed.
There are obtained 2.2 g (90.3 %) of the desired compound, m.p.
190-1~2C.
Another advantage of the process of the invention over knownprocesses for synthetizing 4-[(2-aminoethyl)-thiomethyl~-5-methyl imidazole i5 that the use of cysteamine hydrohalide is avoided.
Instead of this expensive chemical, a 2-haloethylamine, preferably 2-chloroethylamine, which is a cheaper and readily available com-pound, is used. Furthermore, there is no need for a preliminary protection of the amino group in this compound.
As organic solvents there can be used polar organic solvents in which the starting reactant is soluble, such as lower alcohols, acetonitrile and the like. The yields of the final compound of the formula I are extraordinarily high and amount to 85 to 90 % of the theoretical yield.
The starting 4(5?-thiomethyl-5(4)-methyl imidazole and the process-es for preparing the same are disclosed in our Belgian patent 875 845.
Since thiols are not very stable compounds, the reactions are preferably carried out in an inert atmosphere.
In an alternative method an alkali mercaptide of 5(4)-methyl-4(5)-thiomethyl imidazole, which is a stable compound, is used as the starting substance. The reaction conditions are similar to those of the previous case.
The invention is illustrated but not limited by the following Examples.
Example 1 S-methyl-4-thiomethyl imidazole (6.4 g, 0.05 mole) is dissolved in t`-~
. ' ',' 1154(;~
ethanol (80 ml). Thereto a 50 % aqueous NaOH solution (10 ml) is added, followed by the addition of hexadecyltributyl phosphonium chloride (1.16 g, 0.0025 mole) and stirring for 10 minutes in an inert atmosphere at room temperature. Over a period of 15 minutes, a solution of 2-chloroethylamine (4.0 g) in ethanol (30 ml) is added and the resùlting mixture is stirred for 30 minutes at room temperature and then for 30 more minutes at 50C. The solvent is removed by evaporation and the residue is extracted with isopropan-ol.
The inorganic salts are filtered off and hydrogen chloride is pass-ed into the isopropanolic solution until pH 1 is reached.
The reaction mixture is evaporated to dryness and the residue is recrystallized from ethanol. There is obtained 3-C(2-aminoethyl) thiomethyl]-5-methyl imidaæole (10.9 g, 89.3 %) in the form of its dihydrochloride, mnp. 189-191C.
ExamPle 2 The procedure of the previous Example is followed, using, however, benzyltriethyl ammonium chloride (TEBA, 580 mg, 2.5 mmole) as the catalyst. There are obtained 10.8 g (88 %) of the desired com-pound.
Example 3 The procedure of Example 1 is followed, using, however, tricaprylyl-methyl ammonium chloride (Aliquat 336, 1.04 g, 2.5 mmole) as the catalyst. There are obtained 10.9 g (89.3 %) of the desired compound.
~1~46) '~
5-methyl-4-thiomethyl imidazole (1.5 g, 0.01 mole) in ~he form of its sodium mercaptide is dissolved in water (20 ml). Thereto benzyltriethyl ammonium chloride (70 mg, 0.3 mmole) is added. The resulting solution is stirred for 10 minutes at room temperature.
Over a period of 10 minutes 2-chloroethylamine (8.0 g) in ethanol (8 ml) is added dropwise to the reaction mixture. The reaction mixture is stirred for 1.5 hours at room temperature, evaporated to dryness and the rest of the procedure of Example 1 is followed.
There are obtained 2.2 g (90.3 %) of the desired compound, m.p.
190-1~2C.
Claims (4)
OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. A process for preparing 4-[(2-aminoethyl)thiomethyl]-5-methyl imidazole of the formula and its acid addition salts, characterized in that a compound of the formula, wherein M represents hydrogen or an alkali metal, is reacted with a 2-haloethylamine, wherein halo represents chloro or bromo, in a system consisting of an aqueous solution of a strong base and of an organic phase, at room temperature in the presence of quaternary ammonium or quaternary phosphon-ium salts as phase transfer catalysts.
2. A process according to claim 1, characterized in that methyl-tricaprylyl ammonium chloride, hexadecyltributyl phosphonium bromide, benzyltriethyl ammonium chloride are used as quater-nary ammonium or quaternary phosphonium salts.
3. A process according to claim 1, characterized in that the reaction is carried out in the presence of a 50 % aqueous sodium hydroxyde solution.
4. A process according to claim 1, characterized in that the reaction is carried out in the presence of lower alcohols or acetonitrile as organic solvents.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| YUP80/80 | 1980-01-14 | ||
| YU80/80A YU41689B (en) | 1980-01-14 | 1980-01-14 | Process for preparing imidazole derivatives |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1154023A true CA1154023A (en) | 1983-09-20 |
Family
ID=25548243
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000368285A Expired CA1154023A (en) | 1980-01-14 | 1981-01-12 | Process for preparing imidazole derivative |
Country Status (10)
| Country | Link |
|---|---|
| JP (1) | JPS56127361A (en) |
| CA (1) | CA1154023A (en) |
| CS (1) | CS214847B2 (en) |
| FI (1) | FI804056L (en) |
| HU (1) | HU187289B (en) |
| NO (1) | NO810083L (en) |
| PL (1) | PL129291B1 (en) |
| SE (1) | SE8100127L (en) |
| SU (1) | SU969159A3 (en) |
| YU (1) | YU41689B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS58188860A (en) * | 1982-04-27 | 1983-11-04 | Fujimoto Seiyaku Kk | Preparation of imidazole derivative |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5440547A (en) * | 1977-09-07 | 1979-03-30 | Seikosha Kk | Device for adjusting output frequency of frequency divider |
| IL56265A (en) * | 1977-12-28 | 1982-08-31 | Om Lab Sa | Process for preparing imidazolyl methylthio guanidine derivatives and a novel intermediate therefor |
-
1980
- 1980-01-14 YU YU80/80A patent/YU41689B/en unknown
- 1980-12-30 FI FI804056A patent/FI804056L/en not_active Application Discontinuation
-
1981
- 1981-01-12 NO NO810083A patent/NO810083L/en unknown
- 1981-01-12 PL PL1981229185A patent/PL129291B1/en unknown
- 1981-01-12 CA CA000368285A patent/CA1154023A/en not_active Expired
- 1981-01-12 CS CS81233A patent/CS214847B2/en unknown
- 1981-01-12 SE SE8100127A patent/SE8100127L/en not_active Application Discontinuation
- 1981-01-13 SU SU813230706A patent/SU969159A3/en active
- 1981-01-13 JP JP275181A patent/JPS56127361A/en active Pending
- 1981-01-13 HU HU8171A patent/HU187289B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| JPS56127361A (en) | 1981-10-06 |
| YU8080A (en) | 1983-10-31 |
| FI804056L (en) | 1981-07-15 |
| SE8100127L (en) | 1981-07-15 |
| SU969159A3 (en) | 1982-10-23 |
| YU41689B (en) | 1987-12-31 |
| HU187289B (en) | 1985-12-28 |
| PL129291B1 (en) | 1984-04-30 |
| CS214847B2 (en) | 1982-06-25 |
| PL229185A1 (en) | 1981-09-18 |
| NO810083L (en) | 1981-07-15 |
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