Organic compounds -- part of the class 532-570 series – Organic compounds – Nitrogen attached directly or indirectly to the purine ring...
Reexamination Certificate
2002-02-07
2003-02-25
Ford, John M. (Department: 1624)
Organic compounds -- part of the class 532-570 series
Organic compounds
Nitrogen attached directly or indirectly to the purine ring...
Reexamination Certificate
active
06525198
ABSTRACT:
The present invention relates to a method for the preparation of 4,6-dichloropyrimidine from 4-chloro-6-methoxypyrimidine. 4,6-Dichloropyrimidine is a valuable intermediate for the preparation of crop protection agents.
A number of methods for preparing 4,6-dichloropyrimidine are known starting from 4,6-dihydroxypyrimidine.
It is also known (see Res. Discl. n 391, 690-691 (1996)) that 4,6-dichloropyrimidine can be reacted by reacting 4-chloro-6-methoxypyrimidine with a chlorinating agent of the formula R
3
PCl
2
. The chlorinating agent can be employed as such or be prepared in situ from a compound of the formula R
3
P═O and phosgene. It is additionally described therein that 4-chloro-6-methoxypyrimidine does not react with phosphorus oxychloride. The disadvantage of this method is that usually only very incomplete conversion can be achieved and thus 4,6-dichloropyrimidine is obtainable only in low yields and low degrees of purity.
A method for the preparation of 4,6-dichloropyrimidine from 4-chloro-6-methoxypyrimidine has now been found and is characterized in that 4-chloro-6-methoxypyrimidine is reacted with at least one sulphur-containing chlorinating agent selected from the group of SCl
2
, SOCl
2
and SO
2
Cl
2
and in the presence of at least one phosphorus compound of the formula
R
3
P═Y
n
(1),
in which
R represents C
1
-C
10
-alkyl or C
6
-C
10
-aryl, each of which may optionally be substituted by up to 5 identical or different substituents from the group of fluorine, chlorine, bromine, C
1
-C
4
-alkyl and C
1
-C
4
-alkoxy,
Y represents oxygen or sulphur
and
n represents zero or 1.
Preferred sulphur-containing chlorinating agents are SOCl
2
and SO
2
Cl
2
, and preferred phosphorus compounds are triphenylphosphine and triphenylphosphine oxide.
Based on 1 mol of 4-chloro-6-methoxypyrimidine it is possible, for example, to employ at least 1 mol of sulphur-containing chlorinating agent. This amount is preferably 1 to 2 mol.
Based on 1 mol of sulphur-containing chlorinating agent it is possible to employ, for example, 0.01 to 1 mol of phosphorus compounds of the formula (1). This amount is preferably 0.02 to 0.25, particularly preferably 0.05 to 0.1, mol.
The method according to the invention is preferably carried out in the presence of a solvent. Suitable examples are aromatic solvents such as toluene, xylenes, chlorobenzene, dichlorobenzenes, chlorotoluenes, benzonitrile and benzotrifluoride, nitrogen-containing solvents such as N-methylpyrrolidone, dimethylformamide, dimethylacetamide and cyclic ureas and oxygen-containing solvents such as ethers, in particular higher-boiling ethers and polyethers. It is also possible to employ mixtures of solvents.
The method according to the invention can be carried out, for example, at temperatures in the range from 50 to 200° C. 75 to 175° C. are preferred, especially 100 to 150° C.
The pressure is in principle not critical. Only if it is wished to employ solvents which boil below the desired reaction temperature at atmospheric pressure is it indicated to operate under elevated pressure so that the solvent is present at least partly in liquid form.
On the assumption that, at the given temperature, no precursors, products and solvents escape from the reaction vessel, the pressure can be, for example, in the range from 0.1 to 5 bar. The pressure is preferably atmospheric, particularly preferably using a solvent which boils under reflux at the required reaction temperature under atmospheric pressure.
The method of the invention can be carried out batchwise and continuously.
In a preferred embodiment of the method according to the invention, 4-chloro-6-methoxypyrimidine, the phosphorus compound and a solvent are mixed, the mixture is heated to the reaction temperature, and then the sulphur-containing chlorinating agent is metered in, where appropriate in a plurality of portions.
The reaction mixture present after the reaction can be worked up, for example, by distilling it through a column, where appropriate under reduced pressure.
It is possible with the method according to the invention to convert 4-chloro-6-methoxypyrimidine into 4,6-dichloropyrimidine in a simple manner. The conversion takes place virtually completely, in contrast to the prior art. This makes it possible to prepare a product with a high 4,6-dichloropyrimidine content in a simple manner. This is desirable because unreacted 4-chloro-6-methoxypyrimidine can be removed only with difficulty by distillation.
REFERENCES:
patent: 745593 (1996-12-01), None
patent: 95/29166 (1995-11-01), None
“Chlorination of Pyrimidines”, Research Disclosure, GB, Industrial Opportunities Ltd., Havant, Nr. 391, Nov. 1, 1996, Seiten 690-691, XP000680903, ISSN: 0374-4353 in der Anmeldung erwähnt Beispiel 2.
Cramm Günther
Klausener Alexander
Mais Franz-Josef
Steffan Guido
Akorli Godfried R.
Bayer Aktiengesellschaft
Ford John M.
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