Method for producing 4,6-dichloropyrimidine

Details Method for producing 4,6-dichloropyrimidine Method for producing 4,6-dichloropyrimidine

2001-12-19

2004-11-23

McKenzie, Thomas (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

06822095

ABSTRACT:

The present invention relates to a process for preparing 4,6-dichloropyrimidine from 4-chloro-6-hydroxypyrimidine. 4,6-Dichloropyrimidine is a valuable intermediate for preparing crop protection agents.
A number of processes for preparing 4,6-dichloropyrimidine are known, see, for example, WO96/23776, EP-A-697 406, EP-A-745 593, WO 95/29166, DE-A-19 53 129 and GB 2 325 224. However, these processes always start 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
.
DE-A44 08 404 describes a process for preparing chloropyrimidines, including inter alia 4,6-dichloropyrimidine. Hydroxypyrimidines are generally mentioned as starting material, but not chlorohydroxypyrimidines. According to this reference, furthermore, chlorination is effected with POCl
3
with addition of amines or amine hydrochlorides.
No process for preparing 4,6-dichloropyrimidine starting from 4-chloro-6 hydroxypyrimidine and resulting in the desired product in a simple manner is yet known.
A process for preparing 4,6-dichloropyrimidine which is characterized in that 4-chloro-6-hydroxypyrimidine is reacted with an acid chloride has now been found.
Suitable acid chlorides are organic and inorganic acid chlorides, for example PCl
3
, POCl
3
, PCl
5
, R—PCl
2
, R—PCl
4
, R—POCl
2
and R
3
PCl
2
, where R represents optionally substituted C
6
-C
10
-aryl or optionally substituted C
1
-C
10
-alkyl, acid chlorides of the formula R′—CO—Cl with R′=chlorine, C
1
-C
10
-alkoxy, C
6
-C
10
-aryloxy, —O—CCl
3
, —CO—Cl, C
5
-C
11
-heteroaryloxy with 1 to 3 heteroatoms from the group of N, O and S, where the alkoxy, aryloxy and hetaryloxy radicals may optionally be substituted, and SOCl
2
.
The acid chlorides are active on their own. In particular, no additions of catalysts are necessary, such as amides (for example diethylformamide), amines or organic phosphorus compounds (see EP-A-95 637).
However, it is possible to add such catalysts which are known in principle.
It is also possible to employ mixtures of acid chlorides, but this is not preferred.
It is furthermore possible to generate the required acid chloride in situ. For example, R
3
PCl
2
can be generated from R
3
P and chlorine or from R
3
P═O and a chlorinating agent, for example PCl
3
, phosgene or SOCl
2
.
It is furthermore possible to employ not only isolated 4-chloro-6-hydroxypyrimidine but also a reaction mixture which contains 4-chloro-6-hydroxypyrimidine and originates, for example, from the cleavage of 4-chloro-6-methoxypyridine. The acid chloride to be employed according to the invention can be metered directly into the reaction mixture from the cleavage of 4-chloro-6-methoxypyrimidine.
In general, at least 1 mol of acid chloride per mole of 4-chloro-6-hydroxypyrimidine is employed in the process of the invention. This amount is preferably 1 to 3 mol.
Solvents suitable in principle are those which have no adverse effect on the reaction to be carried out. Examples are aliphatic solvents such as alkanes, cycloalkanes and halogenoalkanes, aromatic solvents such as benzene, xylenes, toluene, chlorobenzenes, benzotrifluoride, p-chlorobenzotrifluoride and anisole, it being possible for the aliphatic and aromatic solvents optionally to be substituted further, nitriles such as acetonitrile and benzonitrile, N-containing solvents such as dimethylformamide, dimethylaceamide, lactams and cyclic ureas, and ethers and polyethers of a wide variety of types. A solvent can be dispensed with if liquid acid chlorides are employed, preferably in excess.
The process of the invention can be carried out, for example, at temperatures in the range 0 to 200° C., preferably at 20 to 175° C., particularly preferably at 30 to 150° C. The pressure is not critical. It can be, for example, 0.1 to 50 bar, preferably 0.5 to 5 bar. Atmospheric pressure is particularly preferred.
The process of the invention can be carried out in various embodiments, for example batchwise, semibatchwise or continuously. One possible procedure is as follows: 4-chloro-6-hydroxypyrimidine is added to an acid chloride with, where appropriate, a solvent. It is then possible to stir at the desired temperature until the conversion to the 4,6-dichloropyrimidine has taken place substantially or completely. It is also possible to meter the acid chloride into 4-chloro-6-hydroxypyrimidine in solution or as suspension. Other procedures are also conceivable.
The working up of the reaction mixture present after the reaction can take place, for example, by extraction of the prepared 4,6-dichloropyrimidine with a solvent and subsequent distillation of the extract. It is also possible to add water to the mixture present after the reaction and then remove 4,6-dichloropyrimidine. It is also possible to distil the complete reaction mixture or firstly carry out a rechlorination with Cl
2
/PCl
3
or PCl
5
and then distil. Other embodiments and possible work ups are also conceivable.
The process of the invention for preparing 4,6-dichloropyrimidine is considerably simpler than the prior art processes. It requires no catalysts or auxiliaries such as amides, organic phosphorus compounds, amines or amine hydrochlorides. It can moreover be carried out without solvent if liquid acid chlorides are used, which greatly simplifies the working up.


REFERENCES:
patent: 5723612 (1998-03-01), Huber et al.
patent: 6608199 (2003-08-01), Doyle et al.
patent: 44 08 404 (1995-09-01), None
patent: 195 31 299 (1997-02-01), None
patent: 196 42 533 (1998-04-01), None
patent: 0 095 637 (1983-12-01), None
patent: 95 637 (1983-12-01), None
patent: 697 406 (1996-02-01), None
patent: 745 593 (1996-12-01), None
patent: 2325224 (1998-11-01), None
patent: 2325224 (1998-11-01), None
patent: 95/29166 (1995-11-01), None
patent: WO 95/29166 (1995-11-01), None
patent: 96/23776 (1996-08-01), None
Pauling, Linus, “General Chemistry, 2ndEd.”, 1953, W.H. Freeman, San Francisco, p. 86.*
Paquette, Leo A. Ed., “Encyclopedia of Reagents for Organic Synthesis, vol. 6”, a995 John Wiley and Sons, New York, p. 1109.*
Dr Rod Beavon, “Rates sometimes fall” Oct. 17, 2003, [online]. London: Westminster School, [retrieved Mar. 17, 2004]. Retreived from the Internet <http://www.rod.beavon.clara.net
itrogenmonoxide.htm>.*
James A. Plambeck, “Termolecular Reactions Are Unlikely” Nov. 16, 1996, [online]. Edmonton, AL: University of Alberta, [retrieved on Mar. 17, 2004]. Retreived from the Internet <http://www.psigate.ac.uk
ewsite/reference/plambeck/chem2/p02156.htm>.*
W. R. Salzman, “Reaction Mechanisms” Mar. 24, 2001, [online]. Tuscon, AZ: University of Arizona, [retrieved on Mar. 17, 2004]. Retreived from the Internet <http://www.chem.arizona.edu/~salzmanr/480a/480ants/reacmech.html>.*
Fred Omega Garces, “Reaction Mechanism Steps of a Reaction” Oct. 16, 2000, [online]. San Diego, CA: Miramar College, [retrieved on Mar. 17, 2004]. Retreived from the Internet <http://www.miramar.sdccd.cc.ca.us/faculty/fgarces/zCourse/Fall2K/Ch201/Ch201Lec/Lectur>.*
Garner, James et al, Heterocyclic Communications, 5(6), 1999, pp. 503-508.*
John D. Roberts and Marjorie C. Caserio, “Basic Principles of Organic Chemistry”, Benjamin, New York, 1964, p 257-259.*
Henry R. Henze, William J. Clegg, Charles W. Smart; J. Org. Chem.; 1952; 17(10); 1320-1327.*
Anonymous: “chlorination of pyrimidines” Research Disclosure Nr. 391, Nov. 1996, Seiten 690-691, XP000680903.
Takao Sakamoto et al.: “Condensed Heteroaromatic Ring Systems VII. Syntheisis of Thienopyridines, Thienopyrimidines, and Furopyridines from o-substituted N-Nheteroarylacetylenes”, Chemical and Pharmaceutical Bulletin, Bd. 34, Nr. 7, 1986, Seiten 2719-2724, XP002066903.
Carroll Temple, Jr., et al.; “Preparation of 2,5-Diamino-4,6-dichloropyrimidine”, Journal of Organic Chemistry, Bd. 40, Nr. 21, 1975, Seiten 3141-3142, XP000566489.
James Garner et al.: “Re

Affiliated with

Also associated with

Rating

Method for producing 4,6-dichloropyrimidine does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Method for producing 4,6-dichloropyrimidine, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Method for producing 4,6-dichloropyrimidine will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-3361411