CA1264754A - Process for the preparation of substituted pyridines - Google Patents

Abstract

ABSTRACT

Substituted pyridines are prepared by the base and transition metal catalyzed ring closure of substituted 5-oxo-pentane-1-nitriles.

Description

PROCESS FOR THE PREPARATION
OF SUBSTITUTED PYRIDINES

This invention relates to the preparation of substituted pyridines by a base and/or transition metal cataly~ed ring closure of substituted 5-oxo-pentane-1--nitriles.

European Patent application 46735 teaches the preparation of chloropyridines substituted by methyl, trichloromethyl or trifluoromethyl groups by adding the appropriate aldehyde to acrylonitrile, methacylonitrile or ~-trifluoromethacrylonitrile in the presence of a catalyst and cyclizing the resulting intermediate in the presence of hydrogen chloride or a substance which forms hydrogen chloride under the reaction conditions.

This invention provides a process Eor preparing compounds having the formula R1 ~ R3 30,687-F -1-7~4 6~693-339 wherein Rl is C'1-C~ alkyl, phenyl, hydrogen or halogen, preferably C1, Br or F, R2 i5 C1 or Br and R3 is Cl, Br or F, ~hich comprises cyclizing a compound having the formula Rl-f-CH2-C-H
CHO CN
wherein R1, R~ and R~ are as above-defined, in the presence of a catalytic amount of an organic amine base and a transi~ion metal catalyst, the reaction being carried out at a temperature in the range of from 25C to 250C in the presence of an inert polar solvent.
The compounds prepared by the process of this invention are advantageously employed as intermediates in the preparation of compounds having insecticidal and~or herbicidal activity as described, for e~ample, ln European Patent Application ~6735.
The reaction may be carried out at any temperature from about room temperaturer e.g., 25C, to 250C, but is preferably carr ed out at temperatures of 70 to 250C and most preferably at temperatures of 200 to 220C.
Any organic base such as, for example, ethylamine, methylamine and cyclohexylamine may be employed, although iso-propylamine is preferred.
The organometallic catalyst may be any transition metal catalyst, such as, for example, Ni(C12) or CoC12(O3P)2. The preferred catalyst is nickel dichlorobis(triphenylphosphine). The reaction is advantageously 7~

carried out in a suitable inert polar solvent, pre-ferably a nitrile solvent and most preferably acetonitrile.

The invention is further illustrated by the following examples.

Example 1 - Prepara-tion of 2,3-dichloro-5-methylpyridine A solution of 32.343 grams of 2,4-dichloro-4--methyl-5-oxopentanenitril~ in 150 ml of acetonitrile and containing 300 mg of nickel dichlorobis(triphenyl-phosphine~ was pumped through a nickel coil havinga volume of about 30 ml at the rate of 2.0-2.5 ml/minu'ce The solution had been preheated to 200-210C at a pressure of 250 psig (1825 kilopascals) Gas chromatographic (G.C.) analysis showed 90% conversion of aldehyde with a 77% yield of

2,3-dichloro-5-methylpyridine.

Example 2 The above experimen~ was repeated except that 30.908 grams of the oxonitrile were used and

3 ml of isopropylamine were included in the solution in addition to the nickel catalyst. Analysis by G.C. showed a conversion of 94.3% and a yield of 23.9 grams (90.1%).

Example 3 The above experiment was repeated except that 31.7 grams of oxonitrile were used and about 1% by weight (3.1 g) of isopropylamine was employed as the sole catalyst. The yield was 80% by G.C.

30,687-F -3-Example 4 A solution of 32.1 grams of 2,4-dichloro-4--methyl-5-oxopentanenltrile in 250 ml of acetonitrile containing 3 ml of isopropylamine and about 300 mg of nickel dichlorobis(triphenylphosphine) was heated to reflux for 48 hours. The excess acetonitrile was then removed by vacuum distillation and the residue flask--distilled at 85-90C at 5 mm Hg on a Kugelrohr. The yield was ~7.0 grams of 2,3~dichloro-5-methylpyridine (86%) isolated as a white solid.

Example 5 A stock solution containing 30 g of 2,4-dichloro-

-4-methyl-5-oxopentane nitrile in 150 ml of acetonitrile was prepared and aliquots of 15-20 ml were withdrawn and charged into 50-ml Fisher-Porter bottles. The indicated catalysts (20 ~l) were then individually added to separate bottles. The reaction mixtures were then placed in an oil bath preheated to 185C
and allowed to react for the indicated time, after which they were analyzed by gas chromatography. The results were as follows:

PERCENT PERCENT
CATALYST TIMECONVERSION YIELD
The Invention Isopropyl amine ~
2 mg CoCl 6H O 1- 1 hour 88 89 2 mg Trip~eny~phosphine t-Butylamine 45 min. 71 75 Aniline 45 min. 84 80 30 Triethylamine 1 hour 86 74 30,687-~ -4-

Claims (6)

THE EMBODIMENTS OF THE INVENTION IN WHICH AN EXCLUSIVE
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:

1. A process for preparing compounds having the formula wherein R1 is a C1-4 alkyl group, a phenyl group or a hydrogen or halogen atom, R2 is a chlorine or bromine atom and R3 is a fluorine, chlorine or bromine atom which comprises cyclizing a compound having the formula wherein R1, R2 and R3 are as above-defined, in the presence of a catalytic amount of an organic amine base and a transition metal catalyst, the reaction being carried out at a temperature in the range of from 25°C to 250°C in the presence of an inert polar solvent.

2. A process as claimed in claim 1 wherein R1 is a methyl group, and R2 and R3 are both chlorine atoms.

3. A process as claimed in claim 1 wherein R1 is an ethyl group and R2 and R3 are both chlorine atoms.

4. A process as claimed in claim 1, 2 or 3 wherein the organic amine base is methylamine, ethylamine, isopropylamine or cyclohexylamine.

5. A process as claimed in claim 1, 2 or 3 wherein the transition metal catalyst is nickel dichlorobis(triphenyl-phosphine).

6. A process as claimed in claim 1, 2 or 3 wherein the temperature is in the range of from 70° to 250°C.