A Publication
of Reliable Methods
for the Preparation
of Organic Compounds
Annual Volume
Org. Synth. 1955, 35, 34
DOI: 10.15227/orgsyn.035.0034
[Pyrimidine, 2-chloro-]
Submitted by Irving C. Kogon, Ronald Minin, and C. G. Overberger1.
Checked by Charles C. Price and T. L. V. Ulbricht.
1. Procedure
Caution! This procedure should be carried out in a good hood.
In a 3-l. three-necked round-bottomed flask fitted with a stirrer and a low-temperature thermometer is placed 500 ml. of concentrated hydrochloric acid (6.0 moles), and the solution is cooled to 0°. To the cooled solution, 142 g. (1.5 moles) of 2-aminopyrimidine (Note 1) is added portionwise with stirring until a homogeneous solution is obtained. The solution is cooled to −15° (Note 2), and a 500-ml. dropping funnel is fitted to the flask. A cold solution of 207 g. (3.0 moles) of sodium nitrite in 375 ml. of water is then added dropwise with stirring over a period of 55 minutes, the reaction temperature being maintained at −15° to −10° (Note 3). The solution is stirred an additional hour, and the temperature is allowed to rise to −5°. The mixture is then carefully neutralized to about pH 7 with a 30% solution of sodium hydroxide (about 3.0 moles), care being taken not to allow the temperature to rise above 0° (Note 4). The solid which forms, consisting of 2-chloropyrimidine and sodium chloride, is collected by filtration and washed thoroughly with ether to dissolve all the 2-chloropyrimidine. The cold solution is extracted with four 75-ml. portions of ether (Note 5). The combined extracts are dried over anhydrous sodium sulfate, the solvent is removed, and the residue is recrystallized from isopentane to give white crystals of 2-chloropyrimidine. The yield is 44–46 g. (26–27%), m.p. 64.5–65.5°.
2. Notes
1. Purchased from the Matheson, Coleman and Bell Company, Norwood, Ohio.
2. Cooling below −15° causes the mixture to solidify.
3. Care should be exercised since at this point nitrogen oxides are being evolved. Addition should be started cautiously, as there tends to be a rapid initial rise in temperature.
4. Yields are appreciably reduced if the temperature is allowed to rise above 0°.
5. Filtration and extraction should be performed immediately or extensive decomposition occurs.
3. Discussion
2-Chloropyrimidine has been prepared by Howard2 and by Sperber, Papa, Schwenk, Sherlock, and Fricano3 by a similar procedure. The compound also has been obtained from 2-hydroxypyrimidine hydrochloride by treatment with a mixture of phosphorus pentachloride and phosphorus oxychloride4 or by treatment with phosphorus oxychloride alone.5 The present procedure has been published.6
This preparation is referenced from:

References and Notes
  1. Polytechnic Institute of Brooklyn, Brooklyn 2, New York.
  2. Howard, U. S. pat. 2,477,409 [C. A., 43, 8105 (1949)].
  3. Sperber, Papa, Schwenk, Sherlock, and Fricano, J. Am. Chem. Soc., 73, 5752 (1951).
  4. Matsukawa and Ohta, J. Pharm. Soc. Japan, 69, 491 (1949) [C. A., 44, 3456 (1950)].
  5. Copenhaver and Kleinschmidt, Brit. pat. 663,302 [C. A., 46, 10212 (1952)].
  6. Overberger and Kogon, J. Am. Chem. Soc., 76, 1065 (1954).

Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)

nitrogen oxides

hydrochloric acid (7647-01-0)

ether (60-29-7)

sodium hydroxide (1310-73-2)

phosphorus pentachloride (10026-13-8)

sodium chloride (7647-14-5)

sodium sulfate (7757-82-6)

sodium nitrite (7632-00-0)

Phosphorus Oxychloride (21295-50-1)

isopentane (78-78-4)

Pyrimidine, 2-chloro- (1722-12-9)

2-aminopyrimidine (109-12-6)

2-hydroxypyrimidine hydrochloride (38353-09-2)