CA1067099A - Process for the production of substituted benzyl cyanides - Google Patents
Process for the production of substituted benzyl cyanidesInfo
- Publication number
- CA1067099A CA1067099A CA279,035A CA279035A CA1067099A CA 1067099 A CA1067099 A CA 1067099A CA 279035 A CA279035 A CA 279035A CA 1067099 A CA1067099 A CA 1067099A
- Authority
- CA
- Canada
- Prior art keywords
- process according
- formula
- cyanide
- phenyl
- schiff
- 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
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
- C07C213/02—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton by reactions involving the formation of amino groups from compounds containing hydroxy groups or etherified or esterified hydroxy groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
INVENTORS
CTIRAD PODESVA
SILVIO IERA
TITLE
PROCESS FOR THE PRODUCTION OF
SUBSTITUTED BENZYL CYANIDES
ABSTRACT OF THE DISCLOSURE
The present invention provides a process for the production of certain 3-lower alkoxy-4-hydroxybenzyl cyanides in which process the anilino moiety of an N-phenyl-3-lower alkoxy 4-hydroxybenzylamine is replaced with a cyanide group by reaction with an alkali metal cyanide. The substituted benzyl cyanides are useful intermediates in the production of pharmacologically active substituted phenyl acetic acid ester.
CTIRAD PODESVA
SILVIO IERA
TITLE
PROCESS FOR THE PRODUCTION OF
SUBSTITUTED BENZYL CYANIDES
ABSTRACT OF THE DISCLOSURE
The present invention provides a process for the production of certain 3-lower alkoxy-4-hydroxybenzyl cyanides in which process the anilino moiety of an N-phenyl-3-lower alkoxy 4-hydroxybenzylamine is replaced with a cyanide group by reaction with an alkali metal cyanide. The substituted benzyl cyanides are useful intermediates in the production of pharmacologically active substituted phenyl acetic acid ester.
Description
6.30.5553 Can.
~067099 Field of Invention =~ _ The present invention relates to the production of substituted benzyl cyanides, in particular 3-lower alkoxy-4-hydroxy-benzyl cyanides. These compounds are useful intermediates in the production of valuable pharmacologically active compounds, especially various substituted phenyl-acetic acids, for example, those described in U.K. patent No. 906,250 and Canadian patent No. 668,696. The best known of these compounds at the present time is 3-methoxy-4-N,N-diethylcarbamoylmethoxy-phenylacetic acid n-propyl ester, commonly referred to as "propanidid". These compounds are considered to be valuable agents for inducing narcosis; in particular, the compounds are capable of inducing a signifi-cant but relatively brief narcotizing effect which enables a treated subject to make a rapid recovery.
Description of Prior Art There are several known processes for producing 3-lower alkoxy-4-hydroxy benzyl cyanides of the general formula:
HO ~ CH2CN ....................... I
OR
wher~ein R is lower alkyl having at most six carbon atoms.
Of particular importance in the present instance is 3-methoxy-4-hydroxy benzyl cyanide which may be used as an intermediate in the production of propanidid. For example, J.H. Short, D.A. Dunnigan, C.W. Ours, Tetrahedron 29, 1931 (1073 et seq) 3~ teaches the reductive alkylation of vanillin according ~67099 to the following scheme:
~0 ~ CH0 + CH3NH2 + H2 -- ~H ~ CH2NHCH3 + H20 C~30 110 - 130C ~ H0 ~ CHzCN + CH3NH2 In German Offenlegungsschrift 2,457,079 there is a discussion of the above process and the disadvantages associated therewith. In an attempt to overcome the disadvantages, the applicant proposes a novel process comprising reacting an N-alkyl benzylamine of formula:
.
H0 ~ CH2NHR
~ ~ OCH3 wherein R is alkyl, with hydrogen cyanide, either in free form or prepared in situ from sodium cyanide, at a temperature of 100-190C. However, this process also leaves something to be desired since, inter alia, the use of hydrogen cyanide~ in any form, is to be avoided if at all possible.
Description of Invention It has now been found that the desired 3-lower alkoxy-4-hydroxy benzyl cyanides of fonmula I can be prepared without the use of hydrogen cyanide (either free or prepared in situ). More specifically it has now been found that the anilino moiety of certain N-phenyl benzylaminescan be converted to the desired nitri~e by reaction of the N-phenyl benzylamlne with an alkali metal cyanide salt.
In one aspect, the present invention provides a method for the production of 3-lower alkoxy-4-hydroxy benzyl cyanides of the formula:
HO ~ CH2CN .......................... I
OR
by reacting an N-phenyl-3-lower alkoxy-4-hydroxy benzylamine of formula II:
HO ~ CH2NH ~ ......................... II
OR
wherein R is lower alkyl with an alkali metal cyanide in a polar solvent.
After completion of the reaction, an agent, usually a metal salt, which reacts with excess cyanide ions to produce an insoluble cyanide, such as cadmium, cobalt and nickel, salts, for example, the metal chlorides, especially .... . ~, .. . . ...
1067(~99 zinc chloride is added to the reaction mixture, usually in an aqueous solution, this resulting in the formation of an insoluble cyanide precipitate which can easily and conveniently be removed by simple filtration. The organic phase remaining is, if necessary, dried and the organic solvent removed by simple distillation at reduced pressure to leave the desired product as an oil which subsequently crystallizes to form a low melting point solid.
Suitable solvents include polar aprotic solvents such as dimethyl formamide and especially dimethylsulphoxide.
Suitable alkyl metal cyanides are sodium and especially potassium cyanide. The reaction may conveniently be effected at a temperature of from 100-150C, especially from 120-140C.
It has been found very advantageous to effect the reaction between the amine and cyanide under an inert atmosphere, such as nitrogen gas, this reducing or even eliminating any undesirable tendencies of the benzylamine reactant and displaced aniline to degrade.
In an especially preferred embodiment of the present invention 4-hydroxy-3-methoxybenzyl cyanide is produced by reacting N-phenylvanillylamine and potassium cyanide in dimethylsulphoxide under a nitrogen atmosphere at a temperature of from 100-150C, preferably 125-135C.
Subsequently the reaction mixture is treated with an aqueous solution of a salt which forms an insoluble cyanide such as zinc chloride, resulting in the cyanide being precipitated. The precipitate is filtered off and the organic solvent removed by distillation under reduced pressure, giving the desired product being obtained as an oil which subsequently solidifies to form a low melting point solid.
The N-phenyl-3-lower alkoxy-4-hydroxy benzylamines of formula II are known compounds and processes for their production may be found in the literature. One very convenient process for producing such compounds has been found to be as follows:
HO ~ CHO + H2N ~ ............ III
R
H~--CH=N_~ , . . . IV
OR
HO ~ C~-N~ ~ .... II
The reduction of the Schiffs base of formula IV to the desired N-phenylbenzylamine of formula II may be effected by methods presently known in the literature and used in the art. However, the reduction is rapidly and conveniently carried out at below ambient temperatures with a metal hydride such as sodium borohydride. Using this route 1067(~99 alternative hydrogenation procedures using hydrogen and expensive catalysts may thereby be avoided.
In a further aspect, the present invention provides a process for the production of 3-lower alkoxy-4-hydroxy benzyl cyanide of formula I wherein a Schiffs base of formula IV:
HO ~ CH=N ~ ................................. IV
OR
wherein R is lower alkyl is reduced by a metal hydride to form the corresponding N-phenyl benzyiamine of formula II:
which is subsequently converted using an alkali metal cyanide in a polar solvent under an inert atmosphere as described above into the desired benzylcyanide of formula I.
This process is very advantageous for producing the preferred 3-methoxy-4-hydroxybenzyl cyanide since vanillin, the starting material for the production of the Schiffs base of formula IV is readily available at relatively - low cost, generally lower for example than the corresponding alcohol. Therefore, not only is the necessary starting ` material (vanillin) relatively inexpensive and the use of hydrogen cyanide avoided, but the process affords very high yields, conversion of N-phenylvanillylamine to 3-methoxy-4-hydroxy benzyl cyanide and conversion of vanillin to N-phenylvanillylamine occurring in yields approaching 90~
giving an overall yield for the multistep embodiment inherent of the process of about 80~ from the readily available vanillin.
1067Q9g It has not previously been ~nown to replace a substitued amino group of formula -NHR with a cyanide group when R is an aryl group. This provides several advantages: for example, aniline is widely used and readily available at relatively low cost; moreover, it has a high boiling point of 185C
which enables the intermediates of formula IV to be produced in a simple liquid medium reaction at high temperatures such as solvent reflux temperatures with virtually no loss of aniline due to evaporation. Moreover, upon the aniline moiety being displaced by the cyanide moiety the non-volatile aniline produced is not lost but is easily recovered for re-use in the process which not only reduces the operating costs of the process but also reduces or eliminates a potential pollution problem, an advantage which is growing in importance as industry as a whole is being forced to reduce the pollution it generates. In the prior art processes discussed above, the displaced molecule is a lower mono alkylamine which generally have relatively low boiling points and high volatilities. For example, the methylamine displaced in the pror art process as discussed above has a boiling point of about -6C and hence, would not prove recoverable and could not be re-used in the process.
.. . . . ........... . .
Preparation of N-Phenylvanillylamine A mixture of 4.65 gm (0.05 mole) of aniline and 7.4 gm (0.5 mole) of vanillin in 37 ml of isopropylalcohol (water oontent less than 0.2%) (by K.F.) were refluxed for two hours. The resulting solution was cooled to 0-5C and 1.9 gm (0.05 mole) of sodiumborohydride was added in portions over a period of 20 minutesl the temperature being :~Q67099 maintained during that period at 0-5C. The suspension resulting was stirred for one hour at 0-5C following which it was-allowed to warm to 20-25C over a period of one hour.
40 Ml of 20% v/v hydrochloric acid was added slowly at 20-25 in portions (to prevent foaming), the pH dropping to 1-2, following which 3S ml of ammonium hydroxide was added, the Ph rising to 9.5-10. The alcohol was stripped from the mixture under reduced pressure, the distillate being arrested when water commenced to distill. To the oily residue,15 ml of water and 100 ml of toluene were added, ,the organic phase separated, washed with brine and dried.
The toluene distilled off under reduced pressure leaving 9.8 gm (86% of theory) of the desired product as an oily residue.
Preparation of 4-Hydroxy-3-MethoxYbenzylcYanide A mixture of 1.86 gm (0.0286 mole) of potassium cyanide and 6 gm (0.026 mole) of N-phenylvanillylamine in 30 ml of dimethylsulfoxide were heated under nitrogen atmosphere at an internal temperature of 125-130C for 19 hours. The dimethylsulfoxide then removed under a reduced pressure (about 20-25 ml of mercury). The residue was cooled and 60 ml of ,, water added resulting in the formation of a dark solution.
0.2 Gm of Norit A*activated carbon was added and the mixture stirred at a pH of about 11 for 30 minutes and then filtered.
A solution of 1.5 gm (0.0143 mole) of zinc chloride and 6 ml of water was added dropwise to'the mixture at 20-25C, this mixture was stirred for a further 20 minutes at a pH of 7, 30 ml of ethyl acetate then added to the suspension which was stirred for a further 20 minutes. The precipitated zinc cyanide was filtered off and the filter cake washed well with *Trade Mark g 1~67099 ethyl acetate. The organic layer separated, washed with brine and dried. Distillation of the ethyl acetate under reduced pressure left 3.75 gm (88~ of theory) of crude 4-hydroxy-3-methoxy-benzylcyanide as an oil, b.p.(0.2-0.3 mm Hg) 127-132C : redistillation of the oil gave a solid m.pt.
48-S0C.
It should be noted that although zinc cyanide is a solid and relative to reagents such as hydrogen cyanide, easily handled, it is a potentially dangerous compound if ingested, inhaled or if it comes into contact with the skin, therefore, normal precautions for the utilization of such basic reagents should be used during the filtration step.
~067099 Field of Invention =~ _ The present invention relates to the production of substituted benzyl cyanides, in particular 3-lower alkoxy-4-hydroxy-benzyl cyanides. These compounds are useful intermediates in the production of valuable pharmacologically active compounds, especially various substituted phenyl-acetic acids, for example, those described in U.K. patent No. 906,250 and Canadian patent No. 668,696. The best known of these compounds at the present time is 3-methoxy-4-N,N-diethylcarbamoylmethoxy-phenylacetic acid n-propyl ester, commonly referred to as "propanidid". These compounds are considered to be valuable agents for inducing narcosis; in particular, the compounds are capable of inducing a signifi-cant but relatively brief narcotizing effect which enables a treated subject to make a rapid recovery.
Description of Prior Art There are several known processes for producing 3-lower alkoxy-4-hydroxy benzyl cyanides of the general formula:
HO ~ CH2CN ....................... I
OR
wher~ein R is lower alkyl having at most six carbon atoms.
Of particular importance in the present instance is 3-methoxy-4-hydroxy benzyl cyanide which may be used as an intermediate in the production of propanidid. For example, J.H. Short, D.A. Dunnigan, C.W. Ours, Tetrahedron 29, 1931 (1073 et seq) 3~ teaches the reductive alkylation of vanillin according ~67099 to the following scheme:
~0 ~ CH0 + CH3NH2 + H2 -- ~H ~ CH2NHCH3 + H20 C~30 110 - 130C ~ H0 ~ CHzCN + CH3NH2 In German Offenlegungsschrift 2,457,079 there is a discussion of the above process and the disadvantages associated therewith. In an attempt to overcome the disadvantages, the applicant proposes a novel process comprising reacting an N-alkyl benzylamine of formula:
.
H0 ~ CH2NHR
~ ~ OCH3 wherein R is alkyl, with hydrogen cyanide, either in free form or prepared in situ from sodium cyanide, at a temperature of 100-190C. However, this process also leaves something to be desired since, inter alia, the use of hydrogen cyanide~ in any form, is to be avoided if at all possible.
Description of Invention It has now been found that the desired 3-lower alkoxy-4-hydroxy benzyl cyanides of fonmula I can be prepared without the use of hydrogen cyanide (either free or prepared in situ). More specifically it has now been found that the anilino moiety of certain N-phenyl benzylaminescan be converted to the desired nitri~e by reaction of the N-phenyl benzylamlne with an alkali metal cyanide salt.
In one aspect, the present invention provides a method for the production of 3-lower alkoxy-4-hydroxy benzyl cyanides of the formula:
HO ~ CH2CN .......................... I
OR
by reacting an N-phenyl-3-lower alkoxy-4-hydroxy benzylamine of formula II:
HO ~ CH2NH ~ ......................... II
OR
wherein R is lower alkyl with an alkali metal cyanide in a polar solvent.
After completion of the reaction, an agent, usually a metal salt, which reacts with excess cyanide ions to produce an insoluble cyanide, such as cadmium, cobalt and nickel, salts, for example, the metal chlorides, especially .... . ~, .. . . ...
1067(~99 zinc chloride is added to the reaction mixture, usually in an aqueous solution, this resulting in the formation of an insoluble cyanide precipitate which can easily and conveniently be removed by simple filtration. The organic phase remaining is, if necessary, dried and the organic solvent removed by simple distillation at reduced pressure to leave the desired product as an oil which subsequently crystallizes to form a low melting point solid.
Suitable solvents include polar aprotic solvents such as dimethyl formamide and especially dimethylsulphoxide.
Suitable alkyl metal cyanides are sodium and especially potassium cyanide. The reaction may conveniently be effected at a temperature of from 100-150C, especially from 120-140C.
It has been found very advantageous to effect the reaction between the amine and cyanide under an inert atmosphere, such as nitrogen gas, this reducing or even eliminating any undesirable tendencies of the benzylamine reactant and displaced aniline to degrade.
In an especially preferred embodiment of the present invention 4-hydroxy-3-methoxybenzyl cyanide is produced by reacting N-phenylvanillylamine and potassium cyanide in dimethylsulphoxide under a nitrogen atmosphere at a temperature of from 100-150C, preferably 125-135C.
Subsequently the reaction mixture is treated with an aqueous solution of a salt which forms an insoluble cyanide such as zinc chloride, resulting in the cyanide being precipitated. The precipitate is filtered off and the organic solvent removed by distillation under reduced pressure, giving the desired product being obtained as an oil which subsequently solidifies to form a low melting point solid.
The N-phenyl-3-lower alkoxy-4-hydroxy benzylamines of formula II are known compounds and processes for their production may be found in the literature. One very convenient process for producing such compounds has been found to be as follows:
HO ~ CHO + H2N ~ ............ III
R
H~--CH=N_~ , . . . IV
OR
HO ~ C~-N~ ~ .... II
The reduction of the Schiffs base of formula IV to the desired N-phenylbenzylamine of formula II may be effected by methods presently known in the literature and used in the art. However, the reduction is rapidly and conveniently carried out at below ambient temperatures with a metal hydride such as sodium borohydride. Using this route 1067(~99 alternative hydrogenation procedures using hydrogen and expensive catalysts may thereby be avoided.
In a further aspect, the present invention provides a process for the production of 3-lower alkoxy-4-hydroxy benzyl cyanide of formula I wherein a Schiffs base of formula IV:
HO ~ CH=N ~ ................................. IV
OR
wherein R is lower alkyl is reduced by a metal hydride to form the corresponding N-phenyl benzyiamine of formula II:
which is subsequently converted using an alkali metal cyanide in a polar solvent under an inert atmosphere as described above into the desired benzylcyanide of formula I.
This process is very advantageous for producing the preferred 3-methoxy-4-hydroxybenzyl cyanide since vanillin, the starting material for the production of the Schiffs base of formula IV is readily available at relatively - low cost, generally lower for example than the corresponding alcohol. Therefore, not only is the necessary starting ` material (vanillin) relatively inexpensive and the use of hydrogen cyanide avoided, but the process affords very high yields, conversion of N-phenylvanillylamine to 3-methoxy-4-hydroxy benzyl cyanide and conversion of vanillin to N-phenylvanillylamine occurring in yields approaching 90~
giving an overall yield for the multistep embodiment inherent of the process of about 80~ from the readily available vanillin.
1067Q9g It has not previously been ~nown to replace a substitued amino group of formula -NHR with a cyanide group when R is an aryl group. This provides several advantages: for example, aniline is widely used and readily available at relatively low cost; moreover, it has a high boiling point of 185C
which enables the intermediates of formula IV to be produced in a simple liquid medium reaction at high temperatures such as solvent reflux temperatures with virtually no loss of aniline due to evaporation. Moreover, upon the aniline moiety being displaced by the cyanide moiety the non-volatile aniline produced is not lost but is easily recovered for re-use in the process which not only reduces the operating costs of the process but also reduces or eliminates a potential pollution problem, an advantage which is growing in importance as industry as a whole is being forced to reduce the pollution it generates. In the prior art processes discussed above, the displaced molecule is a lower mono alkylamine which generally have relatively low boiling points and high volatilities. For example, the methylamine displaced in the pror art process as discussed above has a boiling point of about -6C and hence, would not prove recoverable and could not be re-used in the process.
.. . . . ........... . .
Preparation of N-Phenylvanillylamine A mixture of 4.65 gm (0.05 mole) of aniline and 7.4 gm (0.5 mole) of vanillin in 37 ml of isopropylalcohol (water oontent less than 0.2%) (by K.F.) were refluxed for two hours. The resulting solution was cooled to 0-5C and 1.9 gm (0.05 mole) of sodiumborohydride was added in portions over a period of 20 minutesl the temperature being :~Q67099 maintained during that period at 0-5C. The suspension resulting was stirred for one hour at 0-5C following which it was-allowed to warm to 20-25C over a period of one hour.
40 Ml of 20% v/v hydrochloric acid was added slowly at 20-25 in portions (to prevent foaming), the pH dropping to 1-2, following which 3S ml of ammonium hydroxide was added, the Ph rising to 9.5-10. The alcohol was stripped from the mixture under reduced pressure, the distillate being arrested when water commenced to distill. To the oily residue,15 ml of water and 100 ml of toluene were added, ,the organic phase separated, washed with brine and dried.
The toluene distilled off under reduced pressure leaving 9.8 gm (86% of theory) of the desired product as an oily residue.
Preparation of 4-Hydroxy-3-MethoxYbenzylcYanide A mixture of 1.86 gm (0.0286 mole) of potassium cyanide and 6 gm (0.026 mole) of N-phenylvanillylamine in 30 ml of dimethylsulfoxide were heated under nitrogen atmosphere at an internal temperature of 125-130C for 19 hours. The dimethylsulfoxide then removed under a reduced pressure (about 20-25 ml of mercury). The residue was cooled and 60 ml of ,, water added resulting in the formation of a dark solution.
0.2 Gm of Norit A*activated carbon was added and the mixture stirred at a pH of about 11 for 30 minutes and then filtered.
A solution of 1.5 gm (0.0143 mole) of zinc chloride and 6 ml of water was added dropwise to'the mixture at 20-25C, this mixture was stirred for a further 20 minutes at a pH of 7, 30 ml of ethyl acetate then added to the suspension which was stirred for a further 20 minutes. The precipitated zinc cyanide was filtered off and the filter cake washed well with *Trade Mark g 1~67099 ethyl acetate. The organic layer separated, washed with brine and dried. Distillation of the ethyl acetate under reduced pressure left 3.75 gm (88~ of theory) of crude 4-hydroxy-3-methoxy-benzylcyanide as an oil, b.p.(0.2-0.3 mm Hg) 127-132C : redistillation of the oil gave a solid m.pt.
48-S0C.
It should be noted that although zinc cyanide is a solid and relative to reagents such as hydrogen cyanide, easily handled, it is a potentially dangerous compound if ingested, inhaled or if it comes into contact with the skin, therefore, normal precautions for the utilization of such basic reagents should be used during the filtration step.
Claims (19)
1. A process for the production of 3-lower alkoxy-4-hydroxy benzyl cyanides of the formula I:
......I
wherein R is lower alkyl;
comprising reacting an N-phenyl 3-lower-alkoxy-4-hydroxy-benzylamine of formula II:
.....II
with an alkali metal cyanide in a polar solvent.
......I
wherein R is lower alkyl;
comprising reacting an N-phenyl 3-lower-alkoxy-4-hydroxy-benzylamine of formula II:
.....II
with an alkali metal cyanide in a polar solvent.
2. Process according to claim 1 wherein the N-phenyl 3-lower alkoxy-4-hydroxybenzylamine of formula II is produced by reducing a Schiff's base of formula IV:
.......IV
wherein R is lower alkyl.
.......IV
wherein R is lower alkyl.
3. Process according to claim 2 wherein the Schiff's base of formula IV is produced by reacting a compound of formula III:
......III
wherein R is lower alkyl;
with aniline.
......III
wherein R is lower alkyl;
with aniline.
4. Process according to claim 1, 2 or 3 wherein the solvent is an aprotic solvent.
5. Process according to claim 1, 2 or 3 wherein the solvent is dimethylformamide.
6. Process as claimed in claim 1, 2 or 3 wherein the reaction between the N-phenyl 3-lower-alkoxy-4-hydroxybenzyl-amine and the alkali metal cyanide is effected under an inert atmosphere.
7. Process as claimed in claim 1, 2 or 3 wherein the reaction between the N phenyl 3-lower alkoxy-4-hydroxybenzyl-amine and the alkali metal cyanide is effected under a nitrogen atmosphere.
8. Process according to claim 1, 2 or 3 wherein the alkali metal cyanide is potassium or sodium cyanide.
9. Process according to claim 2 or 3 wherein the Schiff's base of formula IV is reduced by a metal hydride in an anhydrous medium.
10. Process for the production of 3 methoxy-4-hydroxybenzyl cyanide comprising reacting N-phenyl 3-methoxy-4-hydroxy-benzylamine with an alkali metal cyanide in a polar solvent.
11. Process according to claim 10 wherein a Schiff's base of formula IVa:
.......IVa is reduced to produce the N-phenyl-3-methoxy-4-hydroxybenzylamine.
.......IVa is reduced to produce the N-phenyl-3-methoxy-4-hydroxybenzylamine.
12. Process according to claim 11 where the Schiff's base of formula IVa is produced by reacting vanillin with aniline.
13. Process according to claim 10, 11 or 12 wherein the polar solvent is aprotic.
14. Process according to claim 10, 11 or 12 wherein the polar solvent is dimethylformamide.
15. Process according to claim 10, 11 or 12 wherein the reaction of vanillin with aniline is effected under an inert atmosphere.
16. Process according to claim 10, 11 or 12 wherein the reaction of vanillin with aniline is effected under a nitrogen atmosphere.
17. Process according to claim 10, 11 or 12 wherein the alkali metal cyanide is potassium cyanide.
18. Process according to claim 11 or 12 wherein the Schiff's base is reduced with a metal hydride in an anhydrous medium.
19. Process according to claim 11 or 12 wherein the Schiff's base is reduced with sodium borohydride.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA279,035A CA1067099A (en) | 1977-05-24 | 1977-05-24 | Process for the production of substituted benzyl cyanides |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA279,035A CA1067099A (en) | 1977-05-24 | 1977-05-24 | Process for the production of substituted benzyl cyanides |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1067099A true CA1067099A (en) | 1979-11-27 |
Family
ID=4108721
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA279,035A Expired CA1067099A (en) | 1977-05-24 | 1977-05-24 | Process for the production of substituted benzyl cyanides |
Country Status (1)
| Country | Link |
|---|---|
| CA (1) | CA1067099A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4388250A (en) | 1982-03-15 | 1983-06-14 | Rhone Poulenc Inc. | Process for the preparation of p-hydroxy-benzyl-nitriles and corresponding amines |
-
1977
- 1977-05-24 CA CA279,035A patent/CA1067099A/en not_active Expired
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4388250A (en) | 1982-03-15 | 1983-06-14 | Rhone Poulenc Inc. | Process for the preparation of p-hydroxy-benzyl-nitriles and corresponding amines |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Mueller-Westerhoff et al. | Synthesis of symmetrically and unsymmetrically substituted. alpha.-diones from organometallic reagents and 1, 4-dialkylpiperazine-2, 3-diones | |
| JPWO2003097632A1 (en) | Propanolamine derivative, method for producing 3-N-methylamino-1- (2-thienyl) -1-propanol, and method for producing propanolamine derivative | |
| CA1067099A (en) | Process for the production of substituted benzyl cyanides | |
| CA1235430A (en) | Process for the preparation of basically substituted phenylacetonitriles | |
| DE1543777B2 (en) | Process for the preparation of alpha low alkyl beta (4 hydroxy phenyl) alanines | |
| CA2136885A1 (en) | Process for preparing imidazopyridine derivatives | |
| JPS60252441A (en) | Naphthalene and naphthoquinone derivative | |
| US5583256A (en) | Process for producing 1,3-dialkyl-2-imidazolidinone | |
| JP3175339B2 (en) | Optically active amine compound, its production method, its intermediate and its use | |
| KR100249593B1 (en) | Ethyl-6-formyloxy-4-hexenoate | |
| US4902831A (en) | Preparation of ethylenediamine derivatives | |
| JP3640319B2 (en) | Method for producing benzamide derivative | |
| JP2659587B2 (en) | 4-aziridinyl pyrimidine derivatives and their production | |
| JP2767295B2 (en) | Method for producing indole-3-carbonitrile compound | |
| JP4667589B2 (en) | Method for producing 2,4-dihydroxypyridine | |
| CA2013080C (en) | Process for the synthesis of the n-methyl-3,4-dimethoxyphenylethylamine | |
| EP2240442B1 (en) | Preparation process useful in synthesis of atorvastatin | |
| US5475140A (en) | Process for producing N,N-disubstituted p-phenylenediamine derivative sulfate | |
| JP4004082B2 (en) | Method for producing cyclic nitroguanidine derivatives | |
| JPS6126786B2 (en) | ||
| JPS62249963A (en) | Manufacture of n-(sulfonylmethyl)formaldehydes | |
| US4053511A (en) | Nopinylamines | |
| JP4218310B2 (en) | Process for producing optically active 2-amino-2-phenylethanol and its intermediate | |
| KR900005255B1 (en) | The process for preparation n-(3-(3-(1-pyperidinyl methyl)phenoxy)propyl)acetoxy acetamide | |
| US4376860A (en) | Pyridyl ketone |