Claims
- 1. A process for the preparation of a 3-phenylpyrrole derivative of formula I ##STR12## wherein X is cyano,--CO---R.sub.3, --CO--OR.sub.3 or ##STR13## R.sub.1 and R.sub.2 are each independently of the other hydrogen, C.sub.1 -C.sub.6 alkyl,
- C.sub.1 -C.sub.6 alkoxy, C.sub.1 14 C.sub.6 alkylthio, nitro, cyano, halogen or C.sub.1 -C.sub.6 -haloalkyl, or
- R.sub.1 and R.sub.2, when taken together, are methylenedioxy or difluoromethylenedioxy,
- R.sub.3 is C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 haloalkyl, phenyl or benzyl, or phenyl or benzyl which are each substituted by halogen, methyl, methoxy or methylthio,
- R.sub.4 is hydrogen, C.sub.1 -C.sub.6 haloalkyl, phenyl or benzyl, or phenyl or benzyl which are each substituted by halogen, methyl, methoxy or methylthio, which process comprises
- (a) reacting N-(p-tolylsulfonyl)methyl formamide, in an inert solvent and in the presence of an organic base, with phosphoroxy chloride, mixing the reaction solution with water, separating the aqueous phase of the resultant two-phase mixture, and
- (b) reacting the organic phase containing (p-tolylsulfonyl)methyl isocyanide direct with a compound of formula II ##STR14## wherein X, R.sub.1 and R.sub.2 are as defined for formula I, Y is --CO--NHR.sub.4, --CO--R.sub.5 or --S--R.sub.5, R.sub.5 is C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 haloalkyl, phenyl or benzyl, or phenyl or benzyl which are each substituted by halogen, methyl, methoxy or methylthio, and R.sub.4 is as defined for formula I, in the presence of a base.
- 2. A process according to claim 1, which comprises
- (a) adding the compound of formula II to the solution of (p-tolylsulfonyl)methyl isocyanide, and
- (b) adding the base to the reaction mixture.
- 3. A process according to claim 1, which comprises adding the base in an amount of 2 to 3 mol per mol of compound of formula II in the reaction of (p-tolylsulfonyl)methyl isocyanide with the compound of formula II.
- 4. A process according to claim 1, wherein R.sub.1 and R.sub.2 are each independently of the other hydrogen, halogen, methoxy or methylthio or, when taken together, are methylenedioxy or difluoromethylenedioxy, R.sub.3 and R.sub.5 are independently of each other C.sub.1 -C.sub.4 alkyl or C.sub.1 -C.sub.4 haloalkyl, R.sub.4 is hydrogen, C.sub.1 -C.sub.4 alkyl or C.sub.1 -C.sub.4 haloalkyl, and Y is --CO--NHR.sub.4 or --CO--R.sub.5.
- 5. A process according to claim 1, wherein the compound of formula II is used in an excess of 10 to 20 mol %, based on the amount of (p-tolylsulfonyl)methyl isocyanide.
- 6. A process according to claim 1, wherein (p-tolylsulfonyl)methyl isocyanide and the compound of formula II are used in equimolar amounts.
- 7. A process according to claim 1, wherein the inert solvent is a compound or a mixture of compounds selected from the group of the open chain or cyclic ethers, chloroalkanes, ketones or from the group of the alkyl esters of lower carbonic acids.
- 8. A process according to claim 1, wherein the inert solvent is a compound or a mixture of compounds selected from the group of the open-chain or cyclic ethers or from the group of the chloroalkanes.
- 9. A process according to claim 1, wherein a tertiary amine is used as base in the reaction of N-(p-tolylsulfonyl)methyl formamide with phosphoroxy chloride.
- 10. A process according to claim 1, wherein an oxide, hydride, hydroxide, carbonate, carboxylic acid salt or alcoholate of an alkali metal or alkaline earth metal, a trialkylamine or a pyridine base is used as base for the reaction of the solution of (p-tolylsulfonyl)methyl isocyanide with the compound of formula II.
- 11. A process according to claim 1, wherein the reaction of the compound of formula II with (p-tolylsulfonyl)methyl isocyanide is carried out in the temperature range from -25.degree. to +25.degree. C.
- 12. A process according to claim 1, wherein the reaction of the compound of formula II with (p-tolylsulfonyl)methyl isocyanide is carried out in the temperature range from -10.degree. to +10.degree. C.
- 13. A process according to claim 10, wherein the base is sodium methylate, sodium ethylate, aqueous sodium hydroxide, aqueous potassium hydroxide, sodium carbonate or potassium carbonate.
- 14. A process according to claim 10, wherein the base is used in an amount of 2 to 2.4 mol per mol of compound of formula II.
- 15. A process according to claim 9, wherein the base is triethylamine.
- 16. A process according to claim 1, wherein the inert solvent is dimethoxymethane, 1,2-dimethoxyethane, diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, methylene chloride, chloroform, carbon tetrachloride or acetic acid ethyl ester.
- 17. A process according to claim 1, wherein the inert solvent is dimethoxymethane, 1,2-dimethoxyethane, diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, methylene chloride, chloroform or carbon tetrachloride.
- 18. A process according to claim 1, wherein the inert solvent is dimethoxymethane, 1,2-dimethoxyethane, tetrahydrofuran, dioxane or acetic acid ethyl ester.
- 19. A process according to claim 1, wherein the inert solvent is dimethoxymethane, 1,2-dimethoxyethane, tetrahydrofuran or dioxane.
- 20. A process according to claim 1, wherein the inert solvent is 1,2-dimethoxyethane and the reaction mixture obtained after the reaction of N-(p-tolylsulfonyl)methyl formamide with phosphoroxy chloride is mixed with the 0.5- to 0.7-fold volume of water.
- 21. A process according to claim 1, wherein the inert solvent is dioxane and the reaction mixture obtained from the reaction of N-(p-tolylsulfonyl)methyl formamide with phosphoroxy chloride is mixed with the 0.2- to 0.35-fold volume of water.
- 22. A process according to claim 1, wherein the inert solvent is tetrahydrofuran and the reaction mixture obtained from the reaction of N-(p-tolylsulfonyl)methyl formamide with phosphoroxy chloride is mixed with the 0.3- to 0.8-fold volume of water.
- 23. A process according to claim 1, wherein the inert solvent is dimethoxymethane and the reaction mixture obtained from the reaction of N-(p-tolylsulfonyl)methyl formamide with phosphoroxy chloride is mixed with the 0.3- to 1.2-fold volume of water.
- 24. A process according to claim 1, wherein X is cyano, --CO--OR.sub.3 or --CO--R.sub.3, R.sub.1 and R.sub.2 are each independently of the other hydrogen, chlorine or, when taken together, are methylenedioxy or difluoromethylenedioxy, R.sub.3 is methyl, Y is --CO--NHR.sub.4 or --CO--R.sub.5, R.sub.4 is hydrogen or methyl, and R.sub.5 is methyl or phenyl.
- 25. A process according to claim 1, which comprises
- (a) carrying out the reaction of N-(p-tolylsulfonyl)methyl formamide with phosphoroxy chloride in 1,2-dimethoxyethane in the presence of triethylamine, mixing the reaction mixture with the 0.55- to 0.6-fold volume of water, separating the aqueous phase from the resultant two-phase reaction mixture, and
- (b) reacting the organic phase containing (p-tolylsulfonyl)methyl isocyanide with the equimolar amount of compound of formula II, based on the amount of (p-tolylsulfonyl)methyl isocyanide, in the presence of 2 to 2.4 mol of aqueous sodium hydroxide, based on the compound of formula II, in the temperature range from -10.degree. to +10.degree. C.
- 26. A process according to claim 22, which comprises
- (a) adding the compound of formula II to the solution of (p-tolylsulfonyl)methyl isocyanide, and
- (b) adding aqueous sodium hydroxide to the reaction mixture.
Parent Case Info
This is a continuation-in-part of my application, Ser. No. 283,341, filed Dec. 12, 1988, now abandoned.
US Referenced Citations (3)
Number |
Name |
Date |
Kind |
4680413 |
Genda et al. |
Jul 1987 |
|
4705801 |
Martin et al. |
Nov 1987 |
|
4778901 |
Martin |
Oct 1988 |
|
Foreign Referenced Citations (2)
Number |
Date |
Country |
0324336 |
Jul 1989 |
EPX |
1030571 |
Feb 1986 |
JPX |
Continuation in Parts (1)
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Number |
Date |
Country |
Parent |
283341 |
Dec 1988 |
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