Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
2001-12-03
2002-06-11
McKane, Joseph K. (Department: 1626)
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
active
06403803
ABSTRACT:
BACKGROUND OF THE INVENTION
The invention relates to a process for working up reaction mixtures comprising 5-aminomethyl-2-chlorothiazole and bis(2-chlorothiazolyl-5-methyl)amine and further relates to bis(2-chlorothiazolyl-5-methyl)amine and its salts.
5-Aminomethyl-2-chlorothiazole (also called AMCT below) is a precursor for the preparation of insecticides and therefore an industrially important intermediate. From EP-A 446,913 and DE-A 196 53 586, it is known that AMCT can be prepared by reacting 5-chloromethyl-2-chloro-thiazole (also called CCMT below) with ammonia according to the
The AMCT is usually separated off from the reaction mixture formed during the conversion by distillation or extraction. In this connection, the multiple pH-controlled extraction with dichloromethane (see examples of DE-A 196 535 86) has proven particularly successful. However, the use of methylene chloride is undesirable on an industrial scale since it is readily volatile and possibly carcinogenic (category C3). Furthermore, an up to six-fold extraction on an industrial scale is associated with considerable expenditure; for reasons of cost and environmental protection, the solvent must be recovered and purified, which in turn is associated with expenditure.
In some instances, the AMCT crude product must, as described in EP-A 446,913, be purified in addition by preparative chromatography. However, the need for preparative chromatography considerably reduces the economic attractiveness of the overall process.
Added to this is the fact that the residues that form during the work-up process of the prior art have not hitherto been passed to a material further processing operation.
The object of the present invention was therefore to provide an improved process for working up reaction mixtures comprising 5-amino-methyl-2-chlorothiazole, which can be obtained by reacting 5-chloro-methyl-2-chlorothiazole with ammonia.
Surprisingly, we have now found that during the reaction of 5-chloromethyl-2-chlorothiazole with ammonia, apart from the desired product AMCT as main by-product, bis(2-chlorothiazolyl-5-methyl)amine (bis-CTMA) of the general formula (II) forms
and that a significantly improved work-up of such reaction mixtures is possible by separating this bis-CTMA in the form of its salts.
SUMMARY OF THE INVENTION
The invention provides a process for working up reaction mixtures comprising 5-aminomethyl-2-chlorothiazole and bis(2-chlorothiazolyl-5-methyl)amine obtained by reacting 5-chloromethyl-2-chlorothiazole with ammonia comprising
(1) separating off any ammonia present in the reaction mixture,
(2) admixing the resultant reaction mixture with an amount of water and an amount of an inorganic acid HX such that at least 85% of the total amount of the bis(2-chlorothiazolyl-5-methyl)amine salt thereby formed precipitates and at least 85% of the total amount of the 5-aminomethyl-2-chlorothiazole salt thereby formed remains in solution, and
(3) separating off the precipitated bis(2-chlorothiazolyl-5-methyl)amine salt.
The invention further provides bis(2-chlorothiazolyl-5-methyl)amine of the general formula (II)
and salts thereof.
In this connection, preference is given primarily to the chloride and the sulfate of bis-CTMA.
DETAILED DESCRIPTION OF THE INVENTION
If the reaction mixture from the preceding conversion of 5-chloro-methyl-2-chlorothiazole with ammonia that is to be used in the process according to the invention still contains excess ammonia, the excess ammonia is first separated from the reaction mixture. This is usually carried out by distillation. In the same way, it is also possible to separate any organic solvent still present in the reaction mixture.
The reaction mixture is then admixed with an amount of water and an amount of an inorganic acid HX such that at least 85% (preferably at least 90%) of the total amount of the secondary ammonium salt of bis-CTMA formed precipitates out, while at least 85% (preferably at least 90%) of the total amount of the primary ammonium salt of AMCT formed remain in solution.
As inorganic acid HX, it is possible to use, for example, HCI, H
2
SO
4
, H
3
PO
4
, or HBr, preference being given to using HCI or H
2
SO
4
. The inorganic acid is expediently used in the form of aqueous solutions of customary concentrations that either are available commercially or else can be readily prepared by dilution of a concentrated form.
The required amount of water and the required amount of acid can be easily determined by the person skilled in the art. Preferably, a total amount of water (i.e., including the water that enters into the reaction mixture via the inorganic acid used) of 60 to 200 ml(preferably 100 to 150 ml of water) is added to the reaction mixture per mole of CCMT, or 55 to 180 ml (preferably 90 to 135 ml) of water, based on the total molar amount of amino thiazoles AMCT and bis-CTMA formed.
It is also possible to carry out the process using an up to 30% molar strength deficit or excess of the inorganic acid, based on the total amount of amino thiazoles AMCT and bis-CTMA formed. Preference is given to carrying out the process using 80 to 100 molar % of inorganic acid, based on the total amount of amino thiazoles AMCT and bis-CTMA formed. In this connection, a pH of 0 to 3 (preferably of 1 to 2) is set. As the reaction temperature, a temperature in the range from 10 to 40° C. (preferably 25 to 30° C.) has proven successful.
During the stirring of the reaction mixture, the salts of the amines AMCT and bis-CTMA form; in the case of the preferred use of HCI, the hydrochloride forms. Here, at least 85% (preferably at least 90%) of the secondary ammonium salt formed precipitates out, while at least 85% (preferably at least 90%) of the primary ammonium salt remains in the mother liquor in high purity, as determined by HPLC.
The solubilities of the ammonium salts of AMCT and bis-CTMA can be influenced within certain limits by adjusting the pH, by adding salts (such as, for example, NaCI or NH
4
CI) or else by adjusting the temperature. Such methods of adjusting solubility are familiar to the average person skilled in the art. In particular, the addition of NaCI in an amount of 10% by weight of the total water phase has proven successful.
The precipitated-out ammonium salt of bis-CTMA can be separated from the reaction mixture virtually completely by filtration, centrifugation, or other mechanical separation methods. The losses of AMCT during this separation are very low and do not impair the economic feasibility of the process.
The salt of bis-CTMA obtained during the separation as residue can be after-washed, for example, with water, dilute hydrochloric acid, NaCI solution, or NH
4
CI solution. The washing solutions that form in the process can be combined with the reaction mixture that has been freed from the bis-CTMA and that contains the AMCT in order to obtain an optimum AMCT yield. Should an even more extensive purification of the bis-CTMA be desired, this is possible, for example, by extraction, chromatography, crystallization, or recrystallization.
An acidic, aqueous solution of the ammonium salt of AMCT is obtained, which can either be further used directly in the next reaction stage or else can be further purified and isolated by known methods (such as evaporation and subsequent recrystallization or extraction, or purification by adsorption etc.). Such a purification is preferred if it is desirable to obtain a product of AMCT that is largely free from inorganic salts or if it is not the salt, but the free base AMCT that is desired.
This varying behavior in the solubility of the ammonium salts of AMCT and bis-CTMA is hitherto unknown, could not have been foreseen, and permits an advantageous work-up of the reaction mixtures used. Using the process according to the invention, bis-CTMA has been found and isolated for the first time.
Bis(2-chlorothiazolyl-5-methyl)amine and its salts, particularly the HCI salt and the hydrate of this HCI salt, can be used as intermediate for the preparation of crop protection compositions, of pharmaceuticals, and of textile d
Anderson Rebecca
Bayer Aktiengesellschaft
Gil Joseph C.
Henderson Richardson E. L.
McKane Joseph K.
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