CA1042915A - 2-iminomethyl-3',4',5'-trimethoxycinnamic acids and esters thereof, and their production - Google Patents
2-iminomethyl-3',4',5'-trimethoxycinnamic acids and esters thereof, and their productionInfo
- Publication number
- CA1042915A CA1042915A CA208,720A CA208720A CA1042915A CA 1042915 A CA1042915 A CA 1042915A CA 208720 A CA208720 A CA 208720A CA 1042915 A CA1042915 A CA 1042915A
- Authority
- CA
- Canada
- Prior art keywords
- formula
- grams
- iminomethyl
- trimethoxycinnamic
- production
- 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
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/48—Two nitrogen atoms
- C07D239/49—Two nitrogen atoms with an aralkyl radical, or substituted aralkyl radical, attached in position 5, e.g. trimethoprim
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/48—Two nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/50—Three nitrogen atoms
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
ABSTRACT OF THE DISCLOSURE
2-Iminomethyl-3',4',5'-trimethoxycinnamic acids and lower alkyl esters thereof are produced by reducing 3,4,5-tri-methoxybenzylidene cyanoacetic acid, or the corresponding ester thereof, in neutral or alkaline medium preferably in a pyridine base as solvent.
2-Iminomethyl-3',4',5'-trimethoxycinnamic acids and lower alkyl esters thereof are produced by reducing 3,4,5-tri-methoxybenzylidene cyanoacetic acid, or the corresponding ester thereof, in neutral or alkaline medium preferably in a pyridine base as solvent.
Description
Z9~5 This invention relates to 2-iminomethyl-3',4',5'-tri-me-thoxycinnamic acid and esters thereof having the formula CH O
~ COOR
~ I ,, 3 ~ ~ CH = C
\ CH = NH
wherein R is a hydrogen atom or an alkyl group having 1-4 carbon atoms, being useful as intermediates in the produc-tion of 2,4-diamino-5-(3',4',5'-trimethoxybenzyl)-pyrimi-dine. The latter is a known compound, also called trimetho- i prim, and has the formula CH~O
3 ~ CH2 ~ ~ 2 Trimethoprim shows a useful antibacterial and sulphon-amide-potentiating effect.
lo The inven-tion also relates to a process for the pro-duction of the compounds of formula I.
It is known that the ethyl ester of 3,4,5-trimethoxy-benzylidene-cyanoacetic acid having the formula CH O
~ . COOC2H5 3 ~ CH = IC III
~ ..
CN
~ CH30 can be reduced in acid medium to form 3,4,5-trimethoxybenzyl-cyanoacetic acid ethyl ester having the formula CH O
,~ COOC2H5 ; 3 ~~ CH2 - CH IV
.\ CN
-L04~
as a colourless oil, and that the said compound can be con-densed with guanidine to form 2,4-diamino-6-hydroxy-5-(3', ; 4',5'-trimethoxybenzyl)-pyrimidine having the formula CH~0. ~ CH2 ~ ~ ~ 2 which again can be converted into trimethoprim by removal of the 6-hydroxy group.
The said known method is disadvantageous in that re-duction of the compound of formula III yields a compound, formula IV 9 which owing to its physical properties is only very difficultly recovered in an even tolerably pure s-tate.
lo This means that the compound of ~ormula V, which is produced by condensation wi-th guanidine, and/or the trimethoprim pro-duced therefrom, has to be subjected to further cost-adding purifications in order to get a pharmaceutically acceptable product The object of the present invention is to overcome the said disadvantage by providing an intermediate suitable ~or the production o~ trimethoprim, which is easily recovered in a pure state by crystallisation, instead of the compound of formula IV.
It has surprisingly been found that this is possible, when using, as an intermediate in the production of trime-thoprim, hitherto unknown 2-iminomethyl-3',4',5'-trime-th-oxycinnamic acid compounds which according to the inven-tion are characterized in having the formula I, wherein R
is a hydrogen atom or an alkyl group having 1-4 c~rbon atoms.
According to the invention, the compounds of ~ormula I
can be produced under mild conditions, at room temperature, . . . ......
~L~4Z9~5 by reduction in a neutral or alkaline medium of 3,4,5-trimethoxy-benzylidene-cyanoacetic acid or an ester thereof of the formula CH30 ~/ r CH =f II
CN
wherein R is a hydrogen atom or an alkyl group having 1-4 carbon atoms. The resulting compound of formula I can be isolated in crystalline form, and it is recovered in quantitative yield. It is thus extremely pure and will give extremely pure products when used as an intermediate in the production of trimethoprim.
The reduction of the compound of formula II may be carried out in any suitable solvent, such as ethanol, but according to the invention particularly good results are obtained by using pyridine bases, preferably picoline, as a solvent.
Trimethoprim can be produced from the present compounds of formula I by first condensing with guanidine to obtain the formerly mentioned 2.4-diamino-6-hydroxy-5-~3',4',5'-trimethoxy-benzyl)-pyrimidine of formula V, which in known manner is converted into trimethoprim by removing the 6-hydroxy group.
In the following the production and use of the present intermediates is illustrated by some Examples.
Example 1
~ COOR
~ I ,, 3 ~ ~ CH = C
\ CH = NH
wherein R is a hydrogen atom or an alkyl group having 1-4 carbon atoms, being useful as intermediates in the produc-tion of 2,4-diamino-5-(3',4',5'-trimethoxybenzyl)-pyrimi-dine. The latter is a known compound, also called trimetho- i prim, and has the formula CH~O
3 ~ CH2 ~ ~ 2 Trimethoprim shows a useful antibacterial and sulphon-amide-potentiating effect.
lo The inven-tion also relates to a process for the pro-duction of the compounds of formula I.
It is known that the ethyl ester of 3,4,5-trimethoxy-benzylidene-cyanoacetic acid having the formula CH O
~ . COOC2H5 3 ~ CH = IC III
~ ..
CN
~ CH30 can be reduced in acid medium to form 3,4,5-trimethoxybenzyl-cyanoacetic acid ethyl ester having the formula CH O
,~ COOC2H5 ; 3 ~~ CH2 - CH IV
.\ CN
-L04~
as a colourless oil, and that the said compound can be con-densed with guanidine to form 2,4-diamino-6-hydroxy-5-(3', ; 4',5'-trimethoxybenzyl)-pyrimidine having the formula CH~0. ~ CH2 ~ ~ ~ 2 which again can be converted into trimethoprim by removal of the 6-hydroxy group.
The said known method is disadvantageous in that re-duction of the compound of formula III yields a compound, formula IV 9 which owing to its physical properties is only very difficultly recovered in an even tolerably pure s-tate.
lo This means that the compound of ~ormula V, which is produced by condensation wi-th guanidine, and/or the trimethoprim pro-duced therefrom, has to be subjected to further cost-adding purifications in order to get a pharmaceutically acceptable product The object of the present invention is to overcome the said disadvantage by providing an intermediate suitable ~or the production o~ trimethoprim, which is easily recovered in a pure state by crystallisation, instead of the compound of formula IV.
It has surprisingly been found that this is possible, when using, as an intermediate in the production of trime-thoprim, hitherto unknown 2-iminomethyl-3',4',5'-trime-th-oxycinnamic acid compounds which according to the inven-tion are characterized in having the formula I, wherein R
is a hydrogen atom or an alkyl group having 1-4 c~rbon atoms.
According to the invention, the compounds of ~ormula I
can be produced under mild conditions, at room temperature, . . . ......
~L~4Z9~5 by reduction in a neutral or alkaline medium of 3,4,5-trimethoxy-benzylidene-cyanoacetic acid or an ester thereof of the formula CH30 ~/ r CH =f II
CN
wherein R is a hydrogen atom or an alkyl group having 1-4 carbon atoms. The resulting compound of formula I can be isolated in crystalline form, and it is recovered in quantitative yield. It is thus extremely pure and will give extremely pure products when used as an intermediate in the production of trimethoprim.
The reduction of the compound of formula II may be carried out in any suitable solvent, such as ethanol, but according to the invention particularly good results are obtained by using pyridine bases, preferably picoline, as a solvent.
Trimethoprim can be produced from the present compounds of formula I by first condensing with guanidine to obtain the formerly mentioned 2.4-diamino-6-hydroxy-5-~3',4',5'-trimethoxy-benzyl)-pyrimidine of formula V, which in known manner is converted into trimethoprim by removing the 6-hydroxy group.
In the following the production and use of the present intermediates is illustrated by some Examples.
Example 1
2-Iminomethyl-3',4',5'--trimethoxycinnamic acid ethyl ester .
58.2 grams (0.2 mole) of 3,4,5-trimethoxy-benzylidene-cyanoacetic acid ethyl ester and 1 gram of Pd/C ~10%) in -" ~L0~29~s 380 ml of 2-picoline were s-tirred at room temperature under a hydrogen pressure of 10 atmospheres, until no more hydro-gen was consumed, when stirring was continued for further two hours. The catalyst was filtered off, and the picoline was evaporated in va uo. The residue was dissolved in 150 ml of hot ethanol. By cooling, 58.5 grams (100%) of 2-~ino-methyl-3',4',5'-trimethoxycinnamic acid ethyl ester with melting point 48-49C crystallized.
lo Example 2 2-Iminometh~1-3',4',5'-trimethoxycinnamic acid ethyl ester 8,73 grams (0.030 mole) of 3,4,5-trimethoxy-benzylidene-cyanoacetic acid ethyl ester were dissolved in 130 ml o,f an-hydrous e-thanol. There was added 0.1 gram palladium on car-bon (10%), and the mixture was placed in a hydrogenation au-toclave. Hydrogen was supplied to a pressure of 11 atmos-pheres, and the reaction mixture was left with stirring, un-til one equivalent of hydrogen had been consumed, when the reaction stopped. Pouring out of the reaction mixture dis-closed that a white subs-tance had crystallized. The mixture was heated to 50C, resulting in the said white substance dissolvin~; the catalyst was filtered off, and 6.31 grams of the white product crystallized by cooling. Partial evapora-tion of the paren-t lye yielded further 2.29 grams, making a total yield of 8.60 grams, 97.0%. After recrystallization from anhydrous eth~nol, the compound melted at 48-49C.
Use of the intermediate in the production of trimetho-prim is illustra-ted by the following Examples.
Example 3 2,4-Diamino-6-hydrox~-5-(31,4',~5'-trimeth~ybenzyl)~ imidine 42~
To a mixture of 14.7 grams (0.050 mole) of the ethyl ester of 2-iminome-thyl-3',4l,5'-trimethoxycinnamic acid and 4.78 grams (0.050 mole) of guanidine hydrochloride in 150 ml of toluene were added 5.4 grams (0.10 mole) o~ sodium methoxide. The reaction mixture was refluxed for 11 hours.
The toluene was removed in vacuo by suction, and the resi-due was dissolved in dilute aqueous sodium hydroxide. Acetic acid was added to the solution to pH 4-6, resulting in the precipitation of an almost white product. The produc-t was lo removed by filtration, washed with water, and dried7 Yield r 13.2 grams, 86.3%.
r Example 4 a) 6-Chloro-2 4-diamino-5-(3' L4~ ,5'-trimethox;ybenz~ pyri-_idine A mixture of 15.6 grams (0.051 mole) of 2,4-diamino-6-hydroxy-5-(3',4',5'-trimethoxybenzyl)-pyrimidine and 75 mI
of phosphorus oxychloride was heated on a steam bath ~or three hours. Excess of phosphorus oxychloride was removed i in vacuo by filtration with suction. Ice was added to the residue, and potassium carbonate was added to pH 8. The pre- P
cipitated substance was filtered off, washed with water, and dried. Yield 14.1 grams~ 85.2%.
After recrystallization from nitromethane, the compound melted at 218.5-220.5C.
b) 2,4-Diamino-5-(3',4't5'-trimethoxybenzYl)-pyrimidine r ~ 8.11 grams (0.025 mole) of 6-chloro-2,4-diamino-5-(3', It `~ 4',5'-trime-thoxybenzyl)-pyrimidine were suspended in 300 ml of 96% ethanol, and 0.6 gram o~ palladium on carbon (5%) was added. Hydrogen at atmospheric pressure was supplied to the suspension. After consumption of one equivalent of hydrogen, ~ Z~L5 the reaction stopped. The reaction mixture was evaporated almost to dryness, and dilute acetic acid was added. The ca-talyst was removed by filtration. Aqueous sodium hydroxide was added to make the parent lye alkaline, whereby 2,4-dia- ;mino-5-(3',4',5'-trimethoxybenzyl)-pyrimidine precipitated.
The compound was removed by filtration, washed with water, and dried. Yield 6.59 grams, 90.9%.
After recrystallization from ethanol, the compound melted at 200.5-202.0C.
lo f Example 5 a) 6-Chloro-2,4-diamino-5-(3' 4' ~-trimethoxybe midine A mixture of 15.6 grams (0.051 mole) of 2,4-diamino-6-hydroxy-5-(3t,4',5'-trimethoxybenzyl)-pyrimidine and 75 ml of phosphorus oxychloride was heated on a steam bath for I four hours. Excess of phosphorus oxychloride was removed I in vacuo by suction. Ice was added to the residue, and po-tassium carbonate was added to pH 8. The precipitated com-pound was sucked off, washed with water, and dried. Yield 14.9 g, 90.0%. ~
b) 2,4-Diami~o-6-hydrazino-~-(3'~4' ~ l, pyrimidine 16.2 grams (0.050 mole) of 6-chloro-2,4-diamino-5-(3'-4',5'-trimethoxybenzyl)-pyrimidine were suspended in 85 ml of hydrazine hydrate. The mixture was refluxed to dissolve ~' the chlorinated compound. After an hour and a half, the reaction mixture was cooled in ice water and the hydrazino derivative crystallized. The compound was filtered from the parent lye and washed with cold methanol on the filter.
Yield 15.1 grams, 94~. Mel ing point 159-162C.
. . .
~Z~S
c) 2,4-Diam no-5-(3'~4'.5'-trimethox~benzyl)-pyrimidine s 8.0 grams (0.025 mole) of 2,4-diamino-6-hydrazino-5-(3',4',5'-trimethoxybenzyl)-pyrimidine were suspended in 100 ml of water. The mixture was heated to 100C, at which temperature 250 ml of a 0.40 M aqueous solution of CuS04 ~;
were added dropwise during 3/4 hour. After the said addition, -the mixture was cooled, and free Cu, precipitated during the reaction, was filtered off. Ammonia was added to make the parent lye alkaline, resulting in the precipitation of a lo greyish green substance, which was removed by filtration, and aqueous sodium hydroxide was added to the parent lye, whereby a further amount of the greyish green substance was precipitated and also filtered off. The two fractions of substance were recrystallized from H20 and activated carbon to yield 6.2 grams, 85.5%, of 2,4-diamino-5-(3i,4~,5'-tri-methoxybenzyl)-pyrimidine with melting point 199.5-201.5C.
~.
.
58.2 grams (0.2 mole) of 3,4,5-trimethoxy-benzylidene-cyanoacetic acid ethyl ester and 1 gram of Pd/C ~10%) in -" ~L0~29~s 380 ml of 2-picoline were s-tirred at room temperature under a hydrogen pressure of 10 atmospheres, until no more hydro-gen was consumed, when stirring was continued for further two hours. The catalyst was filtered off, and the picoline was evaporated in va uo. The residue was dissolved in 150 ml of hot ethanol. By cooling, 58.5 grams (100%) of 2-~ino-methyl-3',4',5'-trimethoxycinnamic acid ethyl ester with melting point 48-49C crystallized.
lo Example 2 2-Iminometh~1-3',4',5'-trimethoxycinnamic acid ethyl ester 8,73 grams (0.030 mole) of 3,4,5-trimethoxy-benzylidene-cyanoacetic acid ethyl ester were dissolved in 130 ml o,f an-hydrous e-thanol. There was added 0.1 gram palladium on car-bon (10%), and the mixture was placed in a hydrogenation au-toclave. Hydrogen was supplied to a pressure of 11 atmos-pheres, and the reaction mixture was left with stirring, un-til one equivalent of hydrogen had been consumed, when the reaction stopped. Pouring out of the reaction mixture dis-closed that a white subs-tance had crystallized. The mixture was heated to 50C, resulting in the said white substance dissolvin~; the catalyst was filtered off, and 6.31 grams of the white product crystallized by cooling. Partial evapora-tion of the paren-t lye yielded further 2.29 grams, making a total yield of 8.60 grams, 97.0%. After recrystallization from anhydrous eth~nol, the compound melted at 48-49C.
Use of the intermediate in the production of trimetho-prim is illustra-ted by the following Examples.
Example 3 2,4-Diamino-6-hydrox~-5-(31,4',~5'-trimeth~ybenzyl)~ imidine 42~
To a mixture of 14.7 grams (0.050 mole) of the ethyl ester of 2-iminome-thyl-3',4l,5'-trimethoxycinnamic acid and 4.78 grams (0.050 mole) of guanidine hydrochloride in 150 ml of toluene were added 5.4 grams (0.10 mole) o~ sodium methoxide. The reaction mixture was refluxed for 11 hours.
The toluene was removed in vacuo by suction, and the resi-due was dissolved in dilute aqueous sodium hydroxide. Acetic acid was added to the solution to pH 4-6, resulting in the precipitation of an almost white product. The produc-t was lo removed by filtration, washed with water, and dried7 Yield r 13.2 grams, 86.3%.
r Example 4 a) 6-Chloro-2 4-diamino-5-(3' L4~ ,5'-trimethox;ybenz~ pyri-_idine A mixture of 15.6 grams (0.051 mole) of 2,4-diamino-6-hydroxy-5-(3',4',5'-trimethoxybenzyl)-pyrimidine and 75 mI
of phosphorus oxychloride was heated on a steam bath ~or three hours. Excess of phosphorus oxychloride was removed i in vacuo by filtration with suction. Ice was added to the residue, and potassium carbonate was added to pH 8. The pre- P
cipitated substance was filtered off, washed with water, and dried. Yield 14.1 grams~ 85.2%.
After recrystallization from nitromethane, the compound melted at 218.5-220.5C.
b) 2,4-Diamino-5-(3',4't5'-trimethoxybenzYl)-pyrimidine r ~ 8.11 grams (0.025 mole) of 6-chloro-2,4-diamino-5-(3', It `~ 4',5'-trime-thoxybenzyl)-pyrimidine were suspended in 300 ml of 96% ethanol, and 0.6 gram o~ palladium on carbon (5%) was added. Hydrogen at atmospheric pressure was supplied to the suspension. After consumption of one equivalent of hydrogen, ~ Z~L5 the reaction stopped. The reaction mixture was evaporated almost to dryness, and dilute acetic acid was added. The ca-talyst was removed by filtration. Aqueous sodium hydroxide was added to make the parent lye alkaline, whereby 2,4-dia- ;mino-5-(3',4',5'-trimethoxybenzyl)-pyrimidine precipitated.
The compound was removed by filtration, washed with water, and dried. Yield 6.59 grams, 90.9%.
After recrystallization from ethanol, the compound melted at 200.5-202.0C.
lo f Example 5 a) 6-Chloro-2,4-diamino-5-(3' 4' ~-trimethoxybe midine A mixture of 15.6 grams (0.051 mole) of 2,4-diamino-6-hydroxy-5-(3t,4',5'-trimethoxybenzyl)-pyrimidine and 75 ml of phosphorus oxychloride was heated on a steam bath for I four hours. Excess of phosphorus oxychloride was removed I in vacuo by suction. Ice was added to the residue, and po-tassium carbonate was added to pH 8. The precipitated com-pound was sucked off, washed with water, and dried. Yield 14.9 g, 90.0%. ~
b) 2,4-Diami~o-6-hydrazino-~-(3'~4' ~ l, pyrimidine 16.2 grams (0.050 mole) of 6-chloro-2,4-diamino-5-(3'-4',5'-trimethoxybenzyl)-pyrimidine were suspended in 85 ml of hydrazine hydrate. The mixture was refluxed to dissolve ~' the chlorinated compound. After an hour and a half, the reaction mixture was cooled in ice water and the hydrazino derivative crystallized. The compound was filtered from the parent lye and washed with cold methanol on the filter.
Yield 15.1 grams, 94~. Mel ing point 159-162C.
. . .
~Z~S
c) 2,4-Diam no-5-(3'~4'.5'-trimethox~benzyl)-pyrimidine s 8.0 grams (0.025 mole) of 2,4-diamino-6-hydrazino-5-(3',4',5'-trimethoxybenzyl)-pyrimidine were suspended in 100 ml of water. The mixture was heated to 100C, at which temperature 250 ml of a 0.40 M aqueous solution of CuS04 ~;
were added dropwise during 3/4 hour. After the said addition, -the mixture was cooled, and free Cu, precipitated during the reaction, was filtered off. Ammonia was added to make the parent lye alkaline, resulting in the precipitation of a lo greyish green substance, which was removed by filtration, and aqueous sodium hydroxide was added to the parent lye, whereby a further amount of the greyish green substance was precipitated and also filtered off. The two fractions of substance were recrystallized from H20 and activated carbon to yield 6.2 grams, 85.5%, of 2,4-diamino-5-(3i,4~,5'-tri-methoxybenzyl)-pyrimidine with melting point 199.5-201.5C.
~.
.
Claims (4)
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. A process for the production of 2-iminomethyl-3', 4',5'-trimethoxycinnamic acid and esters thereof of the formula I
wherein R is a hydrogen atom or an alkyl group having 1-4 carbon atoms, which comprises reducing 3,4,5-trimethoxybenzylidene-cyanoacetic acid or an ester thereof of the formula II
wherein R is as hereinbefore defined in a neutral or alkaline medium.
wherein R is a hydrogen atom or an alkyl group having 1-4 carbon atoms, which comprises reducing 3,4,5-trimethoxybenzylidene-cyanoacetic acid or an ester thereof of the formula II
wherein R is as hereinbefore defined in a neutral or alkaline medium.
2. A process according to claim 1, characterized in that the reduction is carried out using a pyridine base as a solvent.
3. A process as claimed in claim 2 in which the pyridine base is picoline.
4. A process as claimed in claim 1 in which R is methyl or ethyl.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DK495973A DK495973A (en) | 1973-09-10 | 1973-09-10 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1042915A true CA1042915A (en) | 1978-11-21 |
Family
ID=8138193
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA208,720A Expired CA1042915A (en) | 1973-09-10 | 1974-09-09 | 2-iminomethyl-3',4',5'-trimethoxycinnamic acids and esters thereof, and their production |
Country Status (9)
| Country | Link |
|---|---|
| JP (1) | JPS5076042A (en) |
| AT (1) | AT336581B (en) |
| CA (1) | CA1042915A (en) |
| DE (1) | DE2443079A1 (en) |
| DK (1) | DK495973A (en) |
| GB (1) | GB1442477A (en) |
| HK (1) | HK12478A (en) |
| KE (1) | KE2806A (en) |
| NL (1) | NL7411932A (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP4918716B2 (en) * | 2005-08-03 | 2012-04-18 | セイコーインスツル株式会社 | Hydrogen generation facility and fuel cell system |
-
1973
- 1973-09-10 DK DK495973A patent/DK495973A/da not_active Application Discontinuation
-
1974
- 1974-09-06 GB GB3898374A patent/GB1442477A/en not_active Expired
- 1974-09-09 JP JP10307774A patent/JPS5076042A/ja active Pending
- 1974-09-09 CA CA208,720A patent/CA1042915A/en not_active Expired
- 1974-09-09 AT AT724374A patent/AT336581B/en active
- 1974-09-09 DE DE19742443079 patent/DE2443079A1/en not_active Withdrawn
- 1974-09-09 NL NL7411932A patent/NL7411932A/en not_active Application Discontinuation
-
1977
- 1977-11-29 KE KE280677A patent/KE2806A/en unknown
-
1978
- 1978-03-02 HK HK12478A patent/HK12478A/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| JPS5076042A (en) | 1975-06-21 |
| NL7411932A (en) | 1975-03-12 |
| DE2443079A1 (en) | 1975-03-20 |
| AT336581B (en) | 1977-05-10 |
| KE2806A (en) | 1978-02-17 |
| ATA724374A (en) | 1976-09-15 |
| HK12478A (en) | 1978-03-10 |
| DK495973A (en) | 1975-05-12 |
| GB1442477A (en) | 1976-07-14 |
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