Organic Process Research & Development 2003, 7, 1040−1042
Safety Aspects of the Under-Pressure Reaction of Trichloroacetyl Chloride and
Acrylonitrile in the Preparation of 3,5,6-Trichloro-2-pyridinol
H. Fakhraian,* A. Bazaz, and H. Hadj-Ghanbary
Department of Chemistry, Imam Hossein UniVersity, Tehran, Iran
a
Abstract:
Table 1. Proportional Composition (%) of the Reaction
b
Mixture of Trichloroacetyl Chloride and Acrylonitrile
The under-pressure reaction of trichloroacetyl chloride (1) with
acrylonitrile (2) in the preparation of 3,5,6-trichloro-2-pyridinol
becomes explosive in certain circumstances. The studies of the
reaction’s enthalpy, the instability of the 2-chloropropionitrile
Under Pressure Conditions
expt
temp (°C)
2
3
4
5
6
7
8
1
2
3
110
150
180
150
40
31
3
1
1
2
16
25
25
26
15
45
(8), and the observation of the unexpected increase of pressure
26
35
5
29
25
30
have helped us to point out that the above feature is due to the
exothermic nature of the reactions and the HCl released by
the 2-chloropropionitrile decomposition at elevated tempera-
ture. So, controlling the temperature and well-done stirring of
the reaction mixture is very important in large-scale production
to avoid the explosion nature of the reaction.
c
4
20
a
1
b
Based on H NMR spectroscopy. Mol ratio of 2:1 was 1.5, and the reaction
lasted for 5 h. c Experiment was performed in CH
CN as solvent.
3
Nevertheless, the one-pot synthesis of 6 by the catalyzed
reaction of 1 with 2 followed by the hydrolysis of the reaction
mixture is a more attractive method, involving less separation
and purification steps. It can be performed under both
atmospheric and pressure conditions.
Introduction
The CuCl-catalyzed reaction of trichloroacetyl chloride
The reaction lasted for 5 h under pressure conditions
because of the conversion rate dependency on the temper-
ature and the possibility of reaching the elevated temperature
(
1) with acrylonitrile (2) is a well-known procedure for the
1
-5
large-scale production of 3,5,6-trichloropyridin-2-ol (6),
a valuable intermediate for the production of chlorpyrifos
(150 °C) in such conditions. Therefore, the same ac-
(insecticide) and triclopyr (herbicide).
complishment of the reaction under atmospheric pressure
The three-step mechanism (addition, cyclization and
6
would be achieved during 30-40 h.
aromatization) was studied and proposed to prepare 6 in high
yield (Scheme 1). 2,2,4-Trichloro-4-cyanobutanoyl chloride
1
In this contribution, we describe the role of solvent and
temperature on the reaction mixture composition, study the
influence of temperature to increase the pressure during the
reaction, and illustrate the causes of a sudden raise of pressure
in certain circumstances.
(3) was produced under atmospheric pressure using nitrogen
stream. The cyclization of 3 catalyzed by HCl under pressure
has led to 3,3,5,6-tetrachloro-3,4-dihydropyridin-2(1H)-one
(
4), and the hydrolysis of 4 has afforded 6.
The formations of the byproducts during the reaction have
6
Results and Discussion
The CuCl-catalyzed reaction of 1 with 2 was performed
under pressure at 110, 150, and 180 °C during 5 h; the
already been discussed. They have been recognized as 3,3,5-
trichloroglutarimide (7) and 2-chloropropionitrile (8) and
have prevented the possibility of carrying out the under-
pressure reaction with high yield and in safe conditions. The
hydrolysis of 2,3,5,6-tetrachloropyridine (5), formed by the
1
mixture constituents were determined by H NMR spectros-
copy and are outlined in the Table 1. Two byproducts (7
and 8) and three products (4, 5, and 6) are formed at different
levels in four performed experiments. Under pressure condi-
tions, we never observed 3, because the reaction proceeded
to the end of the cyclization step (i.e., formation of 4).
At 110 °C, more than one-third of 2 was left unchanged;
the reaction was halted at the end of the second step, and 4
was formed. At a more elevated temperature (150 °C), the
conversion rate was increased and the reaction was performed
until the end of the aromatization step. The products 5 and
6 were formed approximately at the same amount. At this
stage, 5 was converted to 6 by hydrolysis of the reaction
mixture via mineral base (e.g., NaOH) under pressure
conditions during 2 h at 150 °C.
chlorination of 6 and 7,7,8 has afforded 6.9
*
Corresponding author. Fax: +98-7313938. E-mail: fakhraian@yahoo.com.
(
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The comparison of the results obtained in experiments 2
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1
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Vol. 7, No. 6, 2003 / Organic Process Research & Development
10.1021/op0340558 CCC: $25.00 © 2003 American Chemical Society
Published on Web 07/19/2003