PROCESS FOR THE PREPARATION OF SUBSTITUTED PYRIDINES

PREPARATION DE PYRIDINES SUBSTITUES

English Abstract

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

Claims

64693-3392
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
<IMG>
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
<IMG>
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
- 5 -

64693-3392
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.
- 6 -

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
12 13
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-

--4--
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-

Representative Drawing