Organic Process Research & Development 2003, 7, 1071−1076
Evaluation and Optimisation of the Reagent Addition Sequence during the
2
4
Synthesis of Atrazine (6-Chloro-N -ethyl-N -isopropyl-1,3,5-triazine-2,4-diamine)
Using Reaction Calorimetry
Benita Barton, Shawn Gouws, Melissa C. Schaefer, and Bernard Zeelie*
Department of Chemistry, Port Elizabeth Technikon, PriVate Bag X6011, Port Elizabeth 6000, South Africa
Abstract:
produce 1. This step is usually carried out at higher
temperatures (<30 °C).
The sequence of reagent addition and associated heats of
reaction during the synthesis of the important herbicide atrazine
(6-chloro-N2-ethyl-N4-isopropyl-1,3,5-triazine-2,4-diamine) from
cyanuric chloride, isopropylamine, and ethylamine have been
investigated by means of calorimetric and analytical methods.
Sodium hydroxide was used as proton scavenger in this
procedure. The best addition sequence found was the concur-
rent addition of amine and NaOH, keeping the amine in slight
excess at all times. Using this feed sequence, the reaction
becomes feed-controlled, and provided that a proper level of
mixing can be maintained in the reactor, a high degree of
control over reaction selectivity is obtained.
One disadvantage of this process is that several side
reactions may occur during the synthesis of 1, leading to
the formation of a number of unwanted side products. The
major impurities that are formed are propazine, 4 (6-chloro-
N2,N4-diisopropyl-1,3,5-triazine-2,4-diamine, Scheme 2), si-
mazine 5 (6-chloro-N2,N4-diethyl-1,3,5-triazine-2,4-diamine,
Scheme 3), hydroxytriazines 6, 7, and 8 (Scheme 3), and
tris-triazines such as 9 (Scheme 4).
In particular, the presence of impurities 4 and 5 in the
final product (although herbicides in their own right) renders
the atrazine product less effective because of their lower
solubilities, thus emphasizing the importance of a highly
efficient and selective method for the production of high-
grade atrazine.
Introduction
Another disadvantage of the industrial process for the
preparation of 1 is that the selectivity and yield of the product
is not consistent from one batch to the next.
Triazines are the most widely used herbicides in the world
today. Atrazine (1) a 1,3,5-triazine, is a selective systemic
herbicide that is used to control broad-leafed weeds and
perennial grasses in crops such as maize, pineapple, and
sugarcane.1 Although there is some debate as to its toxicity
and impact on the environment, the use of atrazine has
numerous advantages over many other herbicides including
a low risk of crop injury (implying higher crop yields) and
low treatment costs.2 Because of these and other positives,
the world market for atrazine is worth over $400 million at
the user level.1 Industrially, atrazine is produced in a two-
stage reaction of cyanuric chloride 2 with isopropylamine
(IPA) and ethylamine in an alkaline medium as has been
described by Pearlman and Banks3 (Scheme 1). The reaction
is exothermic and is carried out in a two-phased mixture of
water and organic solvent (typically xylene or toluene). The
water acts as a heat sink, as a reactant carrier for the amines
and sodium hydroxide, and as a solvent for the byproduct,
sodium chloride. The organic solvent acts as a solvent/
dispersant for the starting material, organic reagents, inter-
mediates, and reaction product.
The purpose of this study was therefore to investigate and
optimise the reagent addition sequence for the synthesis of
atrazine such that the product may consistently meet technical
specifications by minimising the formation of side products
as far as possible. For this purpose, reaction calorimetry was
used to monitor the rate of reaction (as a function of total
energy released). These results were compared to those
obtained for the chemical analysis [high performance liquid
chromatography (HPLC)] of reaction mixtures to define the
most suitable addition sequence.
In this investigation, power compensation calorimetry was
selected as the most appropriate technique with which to
study this reaction, whereby a constant temperature dif-
ferential (∆T ≈ 10-30 °C) is set up between the reactor
contents (reaction mixture) and the reactor jacket. This is
achieved through the use of an internal heater to heat and
keep the reaction mixture at the desired temperature. The
jacket temperature (controlled via an external heating/cooling
system) is set at the desired lower temperature. The principles
of power compensation calorimetry4,5 are best illustrated by
means of the schematic representation of the experimental
arrangement shown in Figure 1.
The least reactive amine, isopropylamine, is first reacted
with 2 to reduce the occurrence of disubstitution of the
organic substrate. To reduce hydrolysis of 2, the reaction
temperature is kept below 5 °C during this step. In the second
step of the reaction, the intermediate, 2,4-dichloro-6-isopro-
pylamine-1,3,5-triazine, 3, is reacted with ethylamine to
Equation 1 summarises the heat balance around the reactor
at the start of the experiment under steady state (before the
(4) Singh, J. Process Saf. Prog. 1997, 16, 43.
(5) Ullman’s Encyclopedia of Industrial Chemistry, 6th ed.; Wiley-VCH:
ullmann/.
(3) Pearlman, W.; Banks, C. K. J. Am. Chem. Soc. 1948, 70, 3726.
10.1021/op0340715 CCC: $25.00 © 2003 American Chemical Society
Published on Web 10/11/2003
Vol. 7, No. 6, 2003 / Organic Process Research & Development
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