Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
2003-03-27
2004-09-07
Stockton, Laura L. (Department: 1626)
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
active
06787654
ABSTRACT:
The invention relates to a process for the preparation of 2-chloro-5-chloromethyl-1,3-thiazole (CCT).
2-Chloro-5-chloromethyl-1,3-thiazole is a valuable intermediate in the preparation of pesticides or pharmaceutical products.
A large number of extremely varied processes for the preparation of CCT are already known from the literature.
For example, EP 0 260 560 and EP 0 446 913 describe the preparation of CCT by reaction of allyl isothiocyanate and of allyl isothiocyanate substituted by a leaving group, respectively, with a chlorinating agent, and EP 0 763 531 describes the reaction of 2-chloroallyl isothiocyanate with a chlorinating agent. Those processes have disadvantages, because, for example in the case of the first variant, a plurality of secondary products are formed so that the CCT prepared has a low degree of purity, and in the case of the second variant the starting material is obtainable only at high cost. Furthermore, a considerable excess of chlorinating agent must be used and the operation must be carried out at a high dilution. In addition, it is necessary to adhere exactly to the reaction temperature and the stable intermediate formed in the course of the reaction has to be converted into the desired end product exothermically in an additional reaction step. As an improvement EP 0 794 180 describes the preparation of CCT from 1,3-dichloropropene and a thiocyanate salt via 3-chloro-1-isothiocyanato-1-propene.
Other variants, for example the process according to EP 0 775 700, according to which CCT is prepared via 2-amino-5-methylthiazole by means of diazotisation and subsequent chlorination, likewise exhibit the disadvantage that CCT is contaminated by a large number of secondary products which can scarcely be removed or can be removed only with great difficulty and with high losses of yield.
The aim of the invention was to provide a new process that enables CCT to be prepared in high purity and high yield.
The invention accordingly relates to a process for the preparation of 2-chloro-5-chloromethyl-1,3-thiazole, wherein allyl isothiocyanate of formula CH
2
═CH—CH
2
—NCS
a) is reacted at from −40° C. to +30° C., in a solvent that is inert under the reaction conditions, with from 1 to 2 mol of a chlorinating agent per mol of allyl isothiocyanate and
b) to the reaction mixture so obtained there is added, at a reaction temperature of from 0° C. to the boiling temperature of the solvent used, from 1 to 5 mol of oxidising agent per mol of allyl isothiocyanate and
c) 2-chloro-5-chloromethyl-1,3-thiazole is isolated from the reaction mixture and
d) is optionally converted by crystallisation into high-purity 2-chloro-5-chloromethyl-1,3-thiazole.
The starting compound used according to the invention for the preparation of CCT is allyl isothiocyanate of formula CH
2
═CH—CH
2
—NCS.
That compound is reacted in step a) with a chlorinating agent.
Chlorinating agents that come into consideration are chlorine and compounds from which chlorine is liberated under the reaction conditions. Examples of such compounds are sulfuryl chloride, PCl
5
, PCl
3
, POCl
3
etc.
The chlorinating agent is used according to the invention in an amount of from 1 to 2 mol per mol of allyl isothiocyanate. Preference is given to the use of from 1 to 1.6 mol and especially from 1 to 1.3 mol of chlorinating agent per mol of allyl isothiocyanate.
The reaction is carried out in a solvent that is inert under the reaction conditions. Suitable solvents are, for example, aliphatic or aromatic hydrocarbons, for example benzene, toluene, hexane, heptane, octane etc., halogenated aliphatic or aromatic hydrocarbons, for example dichloromethane, 1,2-dichloroethane, carbon tetrachloride, 1,1,2,2-tetrachloroethane, trichloromethane and trichloroethane, chlorobenzene, dichlorobenzenes, trichlorobenzene etc., ethers, for example diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, etc., nitriles, for example acetonitrile, propionitrile, etc., amides, for example dimethylformamide, methylpyrrolidone, diethylformamide, etc., sulfoxides, for example dimethyl sulfoxide etc.
Preference is given to halogenated, aliphatic or aromatic solvents from the group dichloromethane, 1,2-dichloroethane, carbon tetrachloride, 1,1,2,2-tetrachloroethane, trichloromethane and trichloroethane, chlorobenzene and dichlorobenzenes.
The reaction temperature is from −40° C. to +30° C., preferably from −30° C. to +10° C. and especially from −20° C. to 0° C.
The reaction mixture is stirred at the appropriate reaction temperature for from a few minutes up to several hours. Stirring is preferably carried out for from about 5 minutes up to 5 hours and especially for from about 20 minutes up to 2 hours.
The reaction of allyl isothiocyanate and chlorinating agent yields an intermediate compound of formula
which is not, however, isolated from the reaction mixture.
The reaction mixture obtained by step a), which contains the above intermediate compound, is immediately after step a) subjected to the following reaction with oxidising agent (step b). For that purpose, in step b) either from 1 to 5 mol of oxidising agent per mol of allyl isothiocyanate are added to the reaction mixture. Suitable oxidising agents are, for example, peroxy acid, for example peracetic acid, m-chloroperbenzoic acid, acid/H
2
O
2
mixtures, inorganic or organic peroxides, for example nickel peroxide, hydroperoxides or quinones, for example dichlorodicyanoquinone.
It is also possible, however, for from 1 to 5 mol of an oxidising agent that acts simultaneously as halogenating agent to be added to the reaction mixture, the oxidation being carried out by halogenation and subsequent dehydrohalogenation. Preferred halogenating agents are chlorinating or brominating compounds, such as Cl
2
, Br
2
, sulfuryl chloride, N-haloimides, for example N-chloro- or N-bromo-succinimide or N-chloro- or N-bromo-phthalimide, or dihalodialkylhydantoins, for example dichlorodimethylhydantoin.
It is preferable to use from 1.2 to 4 mol and especially from 1.8 to 3 mol of oxidising agent or halogenating agent per mol of allyl isothiocyanate.
The oxidising agent or halogenating agent used is preferably a chlorinating or brominating compound and especially N-chloro- or N-bromo-succinimide, N-chloro- or N-bromo-phthalimide and dichlorodimethylhydantoin.
When a halogenating compound is used as oxidising agent, substitution takes place which, for example, is initiated or accelerated by UV light and/or by addition of a suitable initiator. Suitable initiators are customary compounds known from the prior art. They are, for example, peroxides, for example dibenzoyl peroxide, diacetyl peroxide, azo compounds, for example azobisisobutyronitrile, etc.
The initiator is used in an amount of from 0.05 to 10 mol %, preferably from 0.1 to 8 mol % and especially from 0.5 to 5 mol %, based on allyl isothiocyanate.
The oxidising agent and/or the initiator can be added either in one portion or divided into several portions.
The reaction temperature is from 0° C. to the boiling point of the solvent used. The reaction temperature is preferably from 20° C. to the boiling point of the solvent used and especially about from 30 to 80° C.
It is especially advantageous to the purity of the CCT when the reactions according to steps a) and b) are carried out under conditions that are as water-free as possible. This is achieved by the use of absolute solvents and pure allyl isothiocyanate, and if necessary by working under an inert gas atmosphere.
For the isolation and working-up of the CCT prepared, the reaction mixture is optionally first cooled.
When a N-haloimide is used as oxidising agent, precipitated imide is separated off, for example, optionally by filtration. The reaction mixture that remains behind is then rendered basic in order to bind any acids present, such as HCI or HBr. This can be carried out, for example, by washing with, or by adding, suitable bases. Suitable bases are, for example, NaHCO
3
solutions, KHCO
3
solutions, Na
2
CO
3
solutions,
Altreiter Johann
Burger Christian
Krich Sylvia
Zwölfer Birgit
Allen Rose M.
Stockton Laura L.
Syngenta Crop Protection Inc.
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