GB1587258A - Production of substituted guanidines - Google Patents
Production of substituted guanidines Download PDFInfo
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- GB1587258A GB1587258A GB2553377A GB2553377A GB1587258A GB 1587258 A GB1587258 A GB 1587258A GB 2553377 A GB2553377 A GB 2553377A GB 2553377 A GB2553377 A GB 2553377A GB 1587258 A GB1587258 A GB 1587258A
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- thiourea
- salt
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- 150000002357 guanidines Chemical class 0.000 title claims description 22
- 238000004519 manufacturing process Methods 0.000 title claims description 10
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 claims description 27
- 150000001875 compounds Chemical class 0.000 claims description 22
- 150000003839 salts Chemical class 0.000 claims description 21
- 238000000034 method Methods 0.000 claims description 20
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 19
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 claims description 15
- ZRALSGWEFCBTJO-UHFFFAOYSA-N anhydrous guanidine Natural products NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 claims description 15
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 claims description 15
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims description 12
- 125000001424 substituent group Chemical group 0.000 claims description 11
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 9
- 125000000217 alkyl group Chemical group 0.000 claims description 9
- 238000002844 melting Methods 0.000 claims description 9
- 230000008018 melting Effects 0.000 claims description 9
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 claims description 8
- 229910052739 hydrogen Inorganic materials 0.000 claims description 7
- 239000001257 hydrogen Substances 0.000 claims description 7
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
- 150000001412 amines Chemical class 0.000 claims description 5
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 5
- 125000004432 carbon atom Chemical group C* 0.000 claims description 4
- 239000007787 solid Substances 0.000 claims description 4
- VLCDUOXHFNUCKK-UHFFFAOYSA-N N,N'-Dimethylthiourea Chemical compound CNC(=S)NC VLCDUOXHFNUCKK-UHFFFAOYSA-N 0.000 claims description 3
- 230000002378 acidificating effect Effects 0.000 claims description 3
- 230000001590 oxidative effect Effects 0.000 claims description 3
- 125000003884 phenylalkyl group Chemical group 0.000 claims description 3
- 159000000000 sodium salts Chemical class 0.000 claims description 3
- 239000002253 acid Substances 0.000 claims description 2
- 125000004429 atom Chemical group 0.000 claims description 2
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 21
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
- 239000000203 mixture Substances 0.000 description 11
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 8
- 239000007864 aqueous solution Substances 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 8
- 239000002244 precipitate Substances 0.000 description 8
- BDHFUVZGWQCTTF-UHFFFAOYSA-N sulfonic acid Chemical compound OS(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-N 0.000 description 8
- 239000011541 reaction mixture Substances 0.000 description 7
- 229920006395 saturated elastomer Polymers 0.000 description 7
- 235000009518 sodium iodide Nutrition 0.000 description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- CRMWDHWPEFVLOU-UHFFFAOYSA-N n,n'-dimethylmethanimidamide Chemical compound CNC=NC CRMWDHWPEFVLOU-UHFFFAOYSA-N 0.000 description 6
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 238000001816 cooling Methods 0.000 description 3
- KDDNKZCVYQDGKE-UHFFFAOYSA-N (2-chlorophenyl)methanamine Chemical compound NCC1=CC=CC=C1Cl KDDNKZCVYQDGKE-UHFFFAOYSA-N 0.000 description 2
- RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical class S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 description 2
- GKVUQZXKYCDPBJ-UHFFFAOYSA-N N-benzyl-N'-methylmethanimidamide Chemical compound C(C1=CC=CC=C1)NC=NC GKVUQZXKYCDPBJ-UHFFFAOYSA-N 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 2
- 210000005036 nerve Anatomy 0.000 description 2
- 238000007790 scraping Methods 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- HWZWLMPFFGWOIJ-UHFFFAOYSA-N 1,2,3-trimethylguanidine;hydroiodide Chemical compound I.CNC(NC)=NC HWZWLMPFFGWOIJ-UHFFFAOYSA-N 0.000 description 1
- ZILSBZLQGRBMOR-UHFFFAOYSA-N 1,3-benzodioxol-5-ylmethanamine Chemical compound NCC1=CC=C2OCOC2=C1 ZILSBZLQGRBMOR-UHFFFAOYSA-N 0.000 description 1
- IDPURXSQCKYKIJ-UHFFFAOYSA-N 1-(4-methoxyphenyl)methanamine Chemical compound COC1=CC=C(CN)C=C1 IDPURXSQCKYKIJ-UHFFFAOYSA-N 0.000 description 1
- APXOHENTPZBQEO-UHFFFAOYSA-N 1-[(2-chlorophenyl)methyl]-2,3-dimethylguanidine;hydroiodide Chemical compound I.CNC(=NC)NCC1=CC=CC=C1Cl APXOHENTPZBQEO-UHFFFAOYSA-N 0.000 description 1
- OLUXTYJVZZRQAL-UHFFFAOYSA-N 1-[(4-methoxyphenyl)methyl]-2,3-dimethylguanidine hydroiodide Chemical compound I.CN\C(NCc1ccc(OC)cc1)=N/C OLUXTYJVZZRQAL-UHFFFAOYSA-N 0.000 description 1
- IBRUMPJVDPHEFZ-UHFFFAOYSA-N 1-benzyl-2,3-dimethylguanidine;hydroiodide Chemical compound I.CNC(=NC)NCC1=CC=CC=C1 IBRUMPJVDPHEFZ-UHFFFAOYSA-N 0.000 description 1
- GDUBTTXVKWIAKV-UHFFFAOYSA-N 1-benzyl-3-methylthiourea Chemical compound CNC(=S)NCC1=CC=CC=C1 GDUBTTXVKWIAKV-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- -1 S-substituted isothiourea Chemical class 0.000 description 1
- FRAKPEDRQISJEU-UHFFFAOYSA-N [I-].C[N+](=C(N)N)C Chemical compound [I-].C[N+](=C(N)N)C FRAKPEDRQISJEU-UHFFFAOYSA-N 0.000 description 1
- 150000001450 anions Chemical group 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 150000002978 peroxides Chemical class 0.000 description 1
- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 150000003585 thioureas Chemical class 0.000 description 1
- RMUKCGUDVKEQPL-UHFFFAOYSA-K triiodoindigane Chemical compound I[In](I)I RMUKCGUDVKEQPL-UHFFFAOYSA-K 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C277/00—Preparation of guanidine or its derivatives, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups
- C07C277/08—Preparation of guanidine or its derivatives, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups of substituted guanidines
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
(54) PRODUCTION OF SUBSTITUTED GUANIDINES
(71) We, AKTIESELSKABET GEA, a Danish Company, of 89 Holger Danskesvej,
DK-2000 Copenhagen F, Denmark, do hereby declare the invention, for which we pray that a patent may be granted to us, and the method by which it is to be performed, to be particularly described in and by the following statement:
This invention relates to a new process for the production of mono-, di- and trisubstituted guanidines of the formula
wherein each of R1, R2, and R3 is hydrogen, an alkyl group, including cycloalkyl, having 1 to 6 carbon atoms, a phenylalkyl group of not more than 3 carbon atoms in the alkyl part, with the proviso that at least one of R1, R2, and R3 shall be different from hydrogen.
Particularly, the compounds of formula I, wherein one of the substitutents R1, R, and R3 is a benzyl group or a phenylethyl group are known and used therapeutically, because they selectively depress symphatetic nerve function and have little or no effect on the parasymphatetic or central nerve functions, cf. the British Patent Specification No. 973,882.
According to the said specification, the compounds may be prepared by the reaction of ammonia or an ammonia derivative or a salt thereof with a S-substituted isothiourea or a salt thereof, for example as follows:
In this scheme, RJ and R2 are as above defined, R is an alkyl group, generally methyl, X is an anion.
The foully smelling mercaptans formed in this process have to be removed completely, which may prove difficult and any way involves a separate purification process.
In the present process, compounds of the. above formula I are produced easily and in good yields from substituted thloureas without formation of the foully smelling mercaptans of the known process.
Thus, according to the invention, there is provided a process for the production of a substituted guanidine having the general formula I, as defined above, or a salt of a said substituted guanidine, including the stages of oxidizing a thiourea or iso-thiourea,
N,N'-substituted with two of the substituents Rl, R2, and R3, or a salt thereof to form the corresponding formamidine-sulphonic acid, and reacting the formamidine-sulphonic acid with the amine of the third of the substitutents R1, R2, and R3, to yield a compound of formula I or a salt thereof, as illustrated by the following schemes of reaction, wherein Rl, R2, and R3 are as hereinbefore defined.
It will be noted that dependent upon the choice of the substituents Rl, R2, and R3, the process will yield mono-, di-or trisubstituted guanidines. Clearly, if the third of the desired substituents R', R2, and R3 is hydrogen, the formamidine-sulphonic acid produced in the first reaction stage is reacted with ammonia in the second reaction stage.
As illustrated by the schemes of reaction, hydrogen peroxide is the preferred oxidizing agent, because it forms water by the reaction, but other peroxides may be used.
Although the salt of a substituted guanidine of formula I may be prepared starting from the salt of a thiourea or iso-thiourea, preferably such a salt is formed by first making the corresponding substituted guanidine of formula I from a thiourea or iso-thiourea and subsequently reacting the substituted guanidine with a sodium salt under acidic conditions to form the required salt.
Several embodiments of the invention will now be more particularly described, by way of example.
EXAMPLE 1
A. N-Benzyl-N' -methylformamidine sulphonic acid
To a mixture of 100 g of 34.6% hydrogen peroxide (1 mole) and 200 ml of water were added 45 g (0.25 mole) of N-benzyl-N'-methylthiourea in small portions during two hours.
The reaction being exothermic, the temperature of the reaction mixture was kept below 18"C by cooling the reaction vessel in a mixture of ice and water.
After the addition of the thiourea derivative, the reaction mixture was left for two hours without cooling, thus slowly reaching room temperature.
Then, it was again cooled in ice-water, whereby the title compound precipitated as white crystals. The crystals were filtered off and washed with a small volume of cold water and finally with ether. The yield was 44 g (0.19 mole), corresponding to 76% of the theoretical yield. The compound melted at 120-1250C under decomposition.
B. N-Benzyl-N',N", dimethylguanidinium iodide
4.56 g (0.020 mole) of N-benzyl-N'-methylformamidine sulphonic acid, a 24% solution of 15 ml methylamine in water, and 50 ml of water were mixed, and the mixture was refluxed for 6 hours. Excess of methylamine was removed by suction in vacuum, after which the volume of the reaction mixture was 50 ml. The mixture was acidified with concentrated hydrochloric acid to a pH between 1 and 2, after which 10 ml of a saturated aqueous solution of NaI and 5 g of solid NaCI were added. The mixture was then left overnight with stirring to yield a cream-coloured precipitate of the title compound. The precipitate was filtered off and recrystallized from ethanol to yield 3.5 g (0.01148 mole), corresponding to 57.4% of the theoretical yield. The melting point was 192-194"C.
EXAMPLE 2
N-Benzyl-N', N"-dimethylguanidinium iodide
A mixture of 3.0 g (0.0197 mole) of N,N'-dimethylformamidine sulphonic acid (produced from N,N'-dimethylthiourea in similar manner as described in step A of Example 1), 10 ml (0.092 mole) of benzylamine and 60 ml of water were mixed and refluxed for 3 1/2 hours.
Concentrated hydrochloric acid was added to a pH between 1 and 2, and then 10 ml of a saturated aqueous solution of NaI were added. After standing for a short time, an almost white precipitate was formed.
The reaction mixture was cooled for about 2 hours in a mixture of ice and water, when the precipitate, consisting of the title compound, was filtered off and recrystallized from ethanol in a yield of 4.7 g (0.0154 mole) (78%) with melting point 192-194 C.
EXAMPLE 3
N-Benzyl-N' -N"-dimethylguanidinium iodide
A mixture of 12 g of N,N'-dimethylformamidine sulphonic acid, 20 ml of benzylamine and 120 ml of water was stirred overnight at room temperature. The mixture was then acidified to pH 1 with hydrochloric acid, and a saturated aqueous solution of sodium iodide was added. After stirring and cooling for about one hour, the precipitate, consisting of the title compound, was filtered off, washed first with water and then with ether, and finally dried at 30"C. The melting point was 195"C, and the yield was 19 g (79%).
EXAMPLE 4
N, N', N"-trimethylguanidinium iodide
15.2 g (0.10 mole) of N,N'-dimethylformamidine sulphonic acid and 75 ml of a 24% aqueous solution of methylamine were dissolved in 250 ml of water. The mixture was refluxed for 3 hours. The surplus of methylamine was sucked off in vacuum, after which concentrated hydrochloric acid was added to give a pH between 1 and 2. Then, a saturated aqueous solution of sodium iodide was added, resulting in a white precipitate of the title compound. The precipitate was removed by filtration and recrystallized from water as shining white needles. The yield was 18.0 g (0.0786 mole, 78.6%) with melting point above 320"C.
EXAMPLE 5 N, N' -dimethyl-N"- (3, 4-methylened ioxybenzyl) -guanidinium iodide
4.56 g (0.030 mole) of N,N'-dimethylformamidine sulphonic acid and 18.1 g (0.12 mole) of 3,4-methylenedioxybenzylamine were dissolved in 60 ml of water, and the solution was refluxed for 4 1/2 hours. The reaction mixture was then concentrated to a volume of 40 ml, after which concentrated hydrochloric acid was added to give a pH between 1 and 3, and then 25 ml of a saturated aqueous solution of sodium iodide were added. A white crystalline precipitate of the title compound was formed, filtered off and washed with water. The yield was 8.4 g (0.0241 mole) corresponding to 80.3% of the theoretical yield, and the melting point was 211.0-212.0"C.
EXAMPLE 6 N- (2-Chlorobenzyl) -N', N"-dimethylguanidinium iodide
4.56 g (0.030 mole) of N,N'-dimethylformamidine sulphonic acid and 17.0 g (0.12 mole) of 2-chlorobenzylamine were dissolved in 60 ml of water, and the solution was refluxed for 5 1/2 hours. The solution was acidified with concentrated hydrochloric acid to pH 1-3 and then 25 ml of a saturated aqueous solution of sodium iodide were added, whereby a yellow oily substance separated. The reaction mixture was stirred overnight, whereby the separated oil became semi-crystalline. The parent lye was decanted off, and the residue was washed repeatedly with ether, whereby all became crystalline. The substance was recrystallized from water, the solution being purified with active carbon, the title compound again separating as an oil which, however, rapidly became crystalline by scraping. The yield of the cream-coloured compound was 6.7 g (0.0197 mole, 65.7%) with melting point 157.5-158.5"C.
EXAMPLE 7
N, N' -dimethyl-N"- (4-methoxybenzyl) -guanidinium iodide
The procedure of Example 6 was repeated using 16.44 g (0.12 mole) of 4methoxybenzylamine instead of 2-chloro-benzylamine. The title compound, also first separating as an oil, wasfinally recovered as a white substance in a yield of 5.8 g (0.0173 mole, 57.7%) with melting point 162.0-162.5"C.
EXAMPLE 8 N-Cyclohexyl-N'-N"-dimethylguanidinium indium iodide 4.56 g (0.030 mole) of N,N'-dimethylformamidine sulphonic acid and 12.0 g (0.12 mole) of cyclohexylamine were dissolved in 60 ml of water. The mixture was stirred overnight and then concentrated by evaporation to a volume of about 30 ml. The reaction mixture was then acidified with hydrochloric acid to pH 2, after which 10 ml of a saturated aqueous solution of sodium iodide were added. An oily substance separated, which rapidly crystallized when scraping. The solid substance was filtered off and recrystallized from water. The white solid, consisting of the title compound, was recovered in a yield of 3.70 g (0.0125 mole, 41.7%) with melting point 195.5-196.0"C.
In the present specification the terms "alkyl group", including "cycloalkyl group", and "phenyl-alkyl group" are understood to mean the corresponding substituted or unsubstituted groups.
WHAT WE CLAIM IS:
1. A process for the production of a substituted guanidine having the general formula:
wherein each of Rl, R2, R3 is hydrogen, an alkyl group, including a cycloalkyl group having 1 to 6 carbon atoms, or a ehenylalkyl group having from 1 to 3 atoms in the alkyl part, at least one Rl, R2, and R being other than hydrogen, or a salt of a said substituted guanidine, including the stages of oxidizing a thiourea or iso-thiourea, N,N'-substituted with two of the substituents R', R2, and R3, of a salt thereof to form the corresponding formamidine-sulphonic acid, and reacting the formamidine-sulphonic acid with the amine of the third of the substituents Rl, R2, and R3 to yield a compound of formula I or a salt thereof.
2. A process according to Claim 1 for the production of a salt of a substituted guanidine having the general formula I as defined above, in which a thiourea or iso-thiourea,
N,N'- substituted with two of the substituents Rl, R2 and R3 is oxidized to form the corresponding formamidine-sulphonic acid, the latter is reacted with the amine of the third of the substituents Rl, R2 and R3 to yield the corresponding compound of formula I and the compound of formula I is reacted with a sodium salt under acidic conditions to form the required salt of the substituted guanidine of general formula I.
3. A process according to Claim 1 or Claim 2, in which hydrogen peroxide is employed to oxidize the said thiourea or iso-thiourea.
4. A process according to Claim 3, in which N, N'-dimethyl-thiourea is oxidized with hydrogen peroxide, and the resulting N,N'-dimethylformamidine-stilphonic acid is reacted with benzylamine.
5. A process according to Claim 1 for the production of a substituted guanidine of the formula I or a salt thereof, substantially as herein described with reference to the examples.
6. Substituted guanidines of the formula I whenever prepared by a process according to any of the preceding claims.
**WARNING** end of DESC field may overlap start of CLMS **.
Claims (6)
1. A process for the production of a substituted guanidine having the general formula:
wherein each of Rl, R2, R3 is hydrogen, an alkyl group, including a cycloalkyl group having 1 to 6 carbon atoms, or a ehenylalkyl group having from 1 to 3 atoms in the alkyl part, at least one Rl, R2, and R being other than hydrogen, or a salt of a said substituted guanidine, including the stages of oxidizing a thiourea or iso-thiourea, N,N'-substituted with two of the substituents R', R2, and R3, of a salt thereof to form the corresponding formamidine-sulphonic acid, and reacting the formamidine-sulphonic acid with the amine of the third of the substituents Rl, R2, and R3 to yield a compound of formula I or a salt thereof.
2. A process according to Claim 1 for the production of a salt of a substituted guanidine having the general formula I as defined above, in which a thiourea or iso-thiourea,
N,N'- substituted with two of the substituents Rl, R2 and R3 is oxidized to form the corresponding formamidine-sulphonic acid, the latter is reacted with the amine of the third of the substituents Rl, R2 and R3 to yield the corresponding compound of formula I and the compound of formula I is reacted with a sodium salt under acidic conditions to form the required salt of the substituted guanidine of general formula I.
3. A process according to Claim 1 or Claim 2, in which hydrogen peroxide is employed to oxidize the said thiourea or iso-thiourea.
4. A process according to Claim 3, in which N, N'-dimethyl-thiourea is oxidized with hydrogen peroxide, and the resulting N,N'-dimethylformamidine-stilphonic acid is reacted with benzylamine.
5. A process according to Claim 1 for the production of a substituted guanidine of the formula I or a salt thereof, substantially as herein described with reference to the examples.
6. Substituted guanidines of the formula I whenever prepared by a process according to any of the preceding claims.
Priority Applications (8)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB2553377A GB1587258A (en) | 1977-06-17 | 1977-06-17 | Production of substituted guanidines |
| NZ18755778A NZ187557A (en) | 1977-06-17 | 1978-06-13 | Preparation of guanidine derivatives |
| DK265978A DK158977C (en) | 1977-06-17 | 1978-06-14 | PROCEDURE FOR MANUFACTURING SUBSTITUTED GUANIDINES OR SALTS THEREOF |
| JP7157778A JPS5448714A (en) | 1977-06-17 | 1978-06-15 | Manufacture of guanidines having substituent |
| AU37154/78A AU520839B2 (en) | 1977-06-17 | 1978-06-15 | Substituted guanidine froma thio-urea |
| CA305,594A CA1083603A (en) | 1977-06-17 | 1978-06-16 | Production of substituted guanidines. |
| NL7806526A NL187856C (en) | 1977-06-17 | 1978-06-16 | METHOD FOR PREPARING SUBSTITUTED GUANIDINS |
| DE19782826452 DE2826452C2 (en) | 1977-06-17 | 1978-06-16 | Process for the preparation of substituted guanidines |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB2553377A GB1587258A (en) | 1977-06-17 | 1977-06-17 | Production of substituted guanidines |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| GB1587258A true GB1587258A (en) | 1981-04-01 |
Family
ID=10229222
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB2553377A Expired GB1587258A (en) | 1977-06-17 | 1977-06-17 | Production of substituted guanidines |
Country Status (8)
| Country | Link |
|---|---|
| JP (1) | JPS5448714A (en) |
| AU (1) | AU520839B2 (en) |
| CA (1) | CA1083603A (en) |
| DE (1) | DE2826452C2 (en) |
| DK (1) | DK158977C (en) |
| GB (1) | GB1587258A (en) |
| NL (1) | NL187856C (en) |
| NZ (1) | NZ187557A (en) |
Cited By (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0195620A2 (en) * | 1985-03-15 | 1986-09-24 | McNeilab, Inc. | Process for producing guanidines such as linogliride and process for intermediates |
| US4656291A (en) * | 1985-03-15 | 1987-04-07 | Mcneilab, Inc. | Process for producing amidine sulfonic acids |
| US4693850A (en) * | 1985-03-15 | 1987-09-15 | Mcneilab, Inc. | Methane sulfonic acid derivatives |
| EP0260118A1 (en) * | 1986-09-10 | 1988-03-16 | Syntex (U.S.A.) Inc. | Selective amidination of diamines |
| US4781866A (en) * | 1985-03-15 | 1988-11-01 | Mcneilab, Inc. | Process for producing amidine sulfonic acid intermediates for guanidines |
| EP0299533A3 (en) * | 1987-07-17 | 1989-07-19 | The Nutrasweet Company | High potency sweetening agents |
| US4851094A (en) * | 1985-03-15 | 1989-07-25 | Mcneilab, Inc. | Process for producing amidine sulfonic acid intermediates for guanidines |
| EP0351350A1 (en) * | 1988-07-12 | 1990-01-17 | THE NUTRASWEET COMPANY (a Delaware corporation) | High potency sweetening agents |
| US5840972A (en) * | 1993-05-06 | 1998-11-24 | Glaxo Wellcome Inc. | Process for preparing NG -monoalkyl-L-arginine and related compounds |
| US5948939A (en) * | 1986-09-10 | 1999-09-07 | Syntex (U.S.A.) Inc. | Selective amidination of diamines |
| CN102363601A (en) * | 2011-09-20 | 2012-02-29 | 科迈化工股份有限公司 | Method for producing rubber accelerator DGP by using hydrogen peroxide as oxidant |
| CN102363602A (en) * | 2011-09-20 | 2012-02-29 | 科迈化工股份有限公司 | Method for producing vulcanization accelerator DPG with hydrogen peroxide as oxidant |
| CN110407720A (en) * | 2019-08-20 | 2019-11-05 | 西安近代化学研究所 | A kind of catalysis of iodine thiocarbamide desulfurization preparation replaces the synthetic method of guanidine |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6043414U (en) * | 1983-08-29 | 1985-03-27 | 本田技研工業株式会社 | Heater devices for motorcycles, etc. |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB973882A (en) * | 1959-12-23 | 1964-10-28 | Wellcome Found | Benzyl-guanidines,their preparation and pharmaceutical compositions containing them |
-
1977
- 1977-06-17 GB GB2553377A patent/GB1587258A/en not_active Expired
-
1978
- 1978-06-13 NZ NZ18755778A patent/NZ187557A/en unknown
- 1978-06-14 DK DK265978A patent/DK158977C/en active
- 1978-06-15 JP JP7157778A patent/JPS5448714A/en active Granted
- 1978-06-15 AU AU37154/78A patent/AU520839B2/en not_active Expired
- 1978-06-16 DE DE19782826452 patent/DE2826452C2/en not_active Expired
- 1978-06-16 CA CA305,594A patent/CA1083603A/en not_active Expired
- 1978-06-16 NL NL7806526A patent/NL187856C/en not_active IP Right Cessation
Cited By (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4851094A (en) * | 1985-03-15 | 1989-07-25 | Mcneilab, Inc. | Process for producing amidine sulfonic acid intermediates for guanidines |
| US4781866A (en) * | 1985-03-15 | 1988-11-01 | Mcneilab, Inc. | Process for producing amidine sulfonic acid intermediates for guanidines |
| US4656270A (en) * | 1985-03-15 | 1987-04-07 | Mcneilab, Inc. | Process for producing guanidines such as linogliride |
| EP0195620A3 (en) * | 1985-03-15 | 1987-08-19 | McNeilab, Inc. | Process for producing guanidines such as linogliride and process for intermediates |
| EP0195620A2 (en) * | 1985-03-15 | 1986-09-24 | McNeilab, Inc. | Process for producing guanidines such as linogliride and process for intermediates |
| US4693850A (en) * | 1985-03-15 | 1987-09-15 | Mcneilab, Inc. | Methane sulfonic acid derivatives |
| US4656291A (en) * | 1985-03-15 | 1987-04-07 | Mcneilab, Inc. | Process for producing amidine sulfonic acids |
| EP0260118A1 (en) * | 1986-09-10 | 1988-03-16 | Syntex (U.S.A.) Inc. | Selective amidination of diamines |
| US5948939A (en) * | 1986-09-10 | 1999-09-07 | Syntex (U.S.A.) Inc. | Selective amidination of diamines |
| EP0299533A3 (en) * | 1987-07-17 | 1989-07-19 | The Nutrasweet Company | High potency sweetening agents |
| EP0351350A1 (en) * | 1988-07-12 | 1990-01-17 | THE NUTRASWEET COMPANY (a Delaware corporation) | High potency sweetening agents |
| US5840972A (en) * | 1993-05-06 | 1998-11-24 | Glaxo Wellcome Inc. | Process for preparing NG -monoalkyl-L-arginine and related compounds |
| CN102363601A (en) * | 2011-09-20 | 2012-02-29 | 科迈化工股份有限公司 | Method for producing rubber accelerator DGP by using hydrogen peroxide as oxidant |
| CN102363602A (en) * | 2011-09-20 | 2012-02-29 | 科迈化工股份有限公司 | Method for producing vulcanization accelerator DPG with hydrogen peroxide as oxidant |
| CN110407720A (en) * | 2019-08-20 | 2019-11-05 | 西安近代化学研究所 | A kind of catalysis of iodine thiocarbamide desulfurization preparation replaces the synthetic method of guanidine |
| CN110407720B (en) * | 2019-08-20 | 2021-07-27 | 西安近代化学研究所 | Synthetic method for preparing substituted guanidine by desulfurizing thiourea under catalysis of iodine |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS5448714A (en) | 1979-04-17 |
| DK158977B (en) | 1990-08-13 |
| DE2826452C2 (en) | 1987-01-22 |
| AU3715478A (en) | 1979-12-20 |
| NL187856B (en) | 1991-09-02 |
| DE2826452A1 (en) | 1979-01-11 |
| JPS5748106B2 (en) | 1982-10-14 |
| CA1083603A (en) | 1980-08-12 |
| AU520839B2 (en) | 1982-03-04 |
| NL7806526A (en) | 1978-12-19 |
| DK265978A (en) | 1978-12-18 |
| DK158977C (en) | 1991-01-21 |
| NZ187557A (en) | 1980-08-26 |
| NL187856C (en) | 1992-02-03 |
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