Claims
- 1. A process for the preparation of a compound of the formula: ##STR31## wherein Z is (C.sub.6 -C.sub.10) aryl or (C.sub.6 -C.sub.10) aryl substituted with up to 3 substituents independently selected from the group consisting of fluoro, chloro, bromo, iodo, nitro, cyano, methoxy, ethoxy, methyl, ethyl, propyl, butyl, trihalomethyl, phenyl and benzoyl; R.sup.1 is (C.sub.1 -C.sub.20) alkyl, (C.sub.3 -C.sub.8) cycloalkyl, (C.sub.3 -C.sub.8) alkenyl, (C.sub.5 -C.sub.8) cycloalkenyl, (C.sub.3 -C.sub.6) alkynyl, phenyl, benzyl or phenethyl or phenyl, benzyl or phenethyl substituted with up to three substituents independently selected from the group consisting of fluoro, chloro, bromo, iodo, nitro, cyano, methoxy, ethoxy, methyl, ethyl and trihalomethyl; R.sup.2 and R.sup.3 are independently hydrogen, (C.sub.1 -C.sub.20) alkyl, phenyl, benzyl or phenethyl or phenyl, benzyl or phenethyl substituted with up to three substituents independently selected from the group consisting of fluoro, chloro, bromo, iodo, nitro, cyano, methoxy, ethoxy, methyl, ethyl and trihalomethyl, or when taken together form (C.sub.4 -C.sub.8) cycloalkyl; R.sup.1 and Z when taken together form the group ##STR32## a is 0 to 5; b is 0 to 5; X is halogen; and c is 0 to 2, which comprises reacting
- (I) a molar equivalent of a benzylcyanide of the formula
- Z--CHR.sup.1 CN
- wherein Z and R.sup.1 are as defined above, and
- (II) about a molar equivalent amount of a dihaloalkane of the formula ##STR33## wherein R.sup.2, R.sup.3, a and b are as defined above and Hal is chlorine, bromine or iodine in the presence of
- (1) about a molar equivalent amount of sodium hydride;
- (2) about a molar equivalent amount of a 50% solution of NaOH; or
- (3) a catalytic amount of a quaternary ammonium halide catalyst of the formula ##STR34## wherein R.sup.4, R.sup.5, R.sup.6 and R.sup.7 are independently (C.sub.1 -C.sub.4) alkyl and Hal is as defined above;
- either neat or in an inert solvent, at temperatures from about 20.degree. C. to about 160.degree. C. to form a arylcyanoalkyl halide of the formula ##STR35## then reacting a molar equivalent of said arylcyanoalkylhalide and (III) about a molar equivalent of an imidazole or an alkali metal salt thereof having the formula ##STR36## wherein Q is hydrogen, sodium, potassium or lithium, in the presence of (1), (2) or (3) above.
- 2. A process according to claim 1 which comprises the additional step of preparing the compound of the formula
- Z--CHR.sup.1 CN
- by reacting
- (A) a molar equivalent of a benzyl cyanide of the formula
- Z--CH.sub.2 CN
- wherein Z is as defined in claim 1 above, and
- (B) about a molar equivalent of an alkylating agent of the formula
- R.sup.1 Hal
- wherein
- R.sup.1 is (C.sub.1 -C.sub.20) alkyl, (C.sub.3 -C.sub.8) cycloalkyl, (C.sub.3 -C.sub.6) alkenyl, (C.sub.5 -C.sub.8) cycloalkenyl, (C.sub.3 -C.sub.6) alkynyl, benzyl or phenethyl or benzyl or phenethyl substituted with up to three substituents independently selected from the group consisting of fluoro, chloro, bromo, iodo, nitro, cyano, methoxy, ethoxy, methyl, ethyl and trihalomethyl and Hal is chlorine, bromine or iodine in the presence of
- (1) about a molar equivalent amount of sodium hydride;
- (2) about molar equivalent amount of a 50% aqueous solution of NaOH; or
- (3) a catalytic amount of a quaternary ammonium halide catalyst of the formula ##STR37## wherein R.sup.3, R.sup.5, R.sup.6 and R.sup.7 are independently (C.sub.1 -C.sub.4) alkyl and Hal is as defined above
- either neat or in an appropriate solvent, at temperature from about 20.degree. C. to about 160.degree. C.
- 3. A process according to claim 1 which comprises the additional step of preparing the compound of the formula
- Z--CHR.sup.1 CN
- by reacting
- (A) a molar amount of an arylaldehyde of the formula
- ZCHO
- wherein Z is as defined in claim 1 above, and
- (B) about a molar equivalent of an aryl magnesium halide of the formula
- R.sup.1 MgHal
- wherein R.sup.1 is phenyl or phenyl substituted with up to three substituents independently selected from the group consisting of fluoro, chloro, bromo, iodo, nitro, cyano, methoxy, ethoxy, methyl, ethyl and trihalomethyl
- in an anhydrous ethereal solvent at temperatures from about 20.degree. C. to about 160.degree. C. to give an arylalkylalcohol of the formula
- Z--CH(R.sup.1) OH
- then reacting a molar equivalent of said arylalkylalcohol, and
- (C) about a molar equivalent of a halogenating agent selected from the group consisting of phosphorous tribromide, phosphorous trichloride and thionyl chloride to form an arylalkylhalide; or
- (D) about a molar equivalent of a methane sulfonate to form a methane sulfonate ester
- in an inert solvent at temperatures from about 20.degree. C. to about 160.degree. C. and then reacting
- (E) a molar equivalent of said arylalkylhalide or said methane sulfonate ester and about a molar equivalent of a metal cyanide selected from sodium, potassium or lithium cyanide in an aprotic solvent, at temperatures from about 20.degree. C. to about 160.degree. C.
- 4. A process according to claim 2 wherein Z is phenyl or phenyl substituted with up to two substituents selected from the group consisting of fluoro, chloro, nitro, methoxy and methyl; R.sup.1 is (C.sub.1 14 C.sub.10) alkyl, (C.sub.3 -C.sub.8) cycloalkyl, (C.sub.5 -C.sub.8) cycloalkenyl, (C.sub.3 -C.sub.6) alkenyl, (C.sub.3 -C.sub.6) alkynyl, benzyl or phenethyl or benzyl or phenethyl substituted with up to 2 substituents selected from the group consisting of chloro, nitro, methoxy and methyl; R.sup.2 and R.sup.3 are independently hydrogen, (C.sub.1 -C.sub.10) alkyl or phenyl; and a, b and c are zero.
- 5. A process according to claim 4 which comprises the additional step of extracting the final product from the reaction mixture with an aqueous mineral acid or organic acid solution.
- 6. A process according to claim 5 which comprises the additional step of basifying the aqueous acid extract and isolating the pure product by filtration or by extraction into an organic solvent and alternatively evaporating it to dryness.
- 7. A process for the preparation of a compound of the formula ##STR38## which comprises: (1) reacting a molar equivalent of benzyl cyanide and about a molar equivalent of 1-chlorobutane in the presence of from about 0.01 to about 10% by weight (based on the benzyl cyanide) of tetrabutylammonium bromide and about a molar equivalent of a 50% aqueous NaOH solution (based on the molar equivalents of 1-chlorobutane) at temperatures from about 20.degree. C. to about 160.degree. C. in an inert solvent and isolating the 2-phenyl-hexanenitrile;
- (2) reacting a molar equivalent of said 2-phenylhexanenitrile and about a molar equivalent of dichloromethane in the presence of from about 0.01 to about 10% by weight (based on the 2-phenylhexanenitrile) of tetrabutylammonium bromide and about a molar equivalent of a 50% aqueous NaOH solution (based on the molar equivalent of dichloromethane) at temperatures from about 20.degree. C. to about 160.degree. C. in an inert solvent and isolating the 1-chloro-2-cyano-2-phenylhexane;
- (3) reacting a molar equivalent of said 1-chloro-2-cyano-2-phenylhexane and about a molar equivalent of imidazole, sodium salt at temperatures from about 20.degree. C. to about 160.degree. C. in an inert solvent and isolating the .alpha.-butyl-.alpha.-phenyl-1H-imidazole-1-propanitrile.
- 8. A process according to claim 7 wherein the inert solvents utilized in step (1) is 1-chlorobutane, in step (2) is dichloromethane and in step (3) is dimethylsulfoxide.
- 9. A process according to claim 7 which comprises the additional step of isolating the .alpha.-butyl-.alpha.-phenyl-1H-imidazole-1-propanitrile by stripping off the inert solvent, treating the reaction mixture with water and an aromatic hydrocarbon separating off the aromatic hydrocarbon and extracting it with an aqueous acid then isolating the pure product by basification followed by filtrating or extracting with an aromatic hydrocarbon and stripping to dryness.
- 10. A process according to claim 9 wherein the acid utilized in the aqueous acid extraction is selected from sulfuric, hydrochloric, phosphoric, nitric, oxalic, citric, tartaric, acetic and formic and the base utilized in the basification step is selected from sodium hydroxide, potassium hydroxide, sodium carbonate, sodium bicarbonate, potassium carbonate and potassium bicarbonate.
- 11. A process for the preparation of a compound of the formula ##STR39## which comprises: (1) reacting a molar equivalent amount of benzylcyanide, about a molar equivalent amount of 1-chlorobutane and about a molar equivalent amount of a 50% aqueous solution of NaOH at from about room temperature to about 50.degree. C.;
- (2) then adding to this reaction mixture about a molar equivalent amount of dibromomethane and isolating the 1-chloro-2-cyano-2-phenylhexane;
- (3) then reacting a molar equivalent amount of said 1-chloro-2-cyano-2-phenylhexane and imidazole either neat or with a high boiling solvent at temperatures from about 50.degree. C. to about 180.degree. C. and isolating the .alpha.-butyl-.alpha.-phenyl-1H-imidazole-1-propanitrile.
- 12. A process according to claim 4 which comprises steps A and B1 of claim 2.
- 13. A process according to claim 4 which comprises steps I, II, 3, and III3 of claim 1.
SUMMARY OF THE INVENTION
This application is a continuation-in-part of application Ser. No. 839,877 filed Oct. 6, 1977, Pat. No. 4,143,137 which is a division of application Ser. No. 647,039 filed Jan. 7, 1976, U.S. Pat. No. 4,073,921 granted Feb. 4, 1978 which in turn is a continuation-in-part of application Ser. No. 557,546 filed Mar. 12, 1975 now abandoned.
US Referenced Citations (2)
Number |
Name |
Date |
Kind |
3732242 |
Buchel et al. |
May 1973 |
|
3755412 |
Taranko et al. |
Aug 1973 |
|
Divisions (1)
|
Number |
Date |
Country |
Parent |
647039 |
Jan 1976 |
|
Continuation in Parts (2)
|
Number |
Date |
Country |
Parent |
839877 |
Oct 1977 |
|
Parent |
557546 |
Mar 1975 |
|