Org. Synth. 1963, 43, 68
DOI: 10.15227/orgsyn.043.0068
2-MERCAPTOPYRIMIDINE
[2-Pyrimidinethiol]
Submitted by Donald G. Crosby, Robert V. Berthold, and Herbert E. Johnson
1.
Checked by B. Bellin, J. L. Gibbs, and V. Boekelheide.
1. Procedure
A. 2-Mercaptopyrimidine hydrochloride. Thiourea (61 g., 0.80 mole) and 600 ml. of ethyl alcohol (Note 1) are placed in a 2-l. three-necked flask equipped with a sealed mechanical stirrer, a reflux condenser, and a stopper. The stirrer is started, and 200 ml. of concentrated hydrochloric acid is added in one portion through the open neck. After several minutes, when the warm mixture has become homogeneous, 176 g. (0.80 mole) of commercial-grade 1,1,3,3-tetraethyoxypropane (Note 2) is added rapidly, the open neck is stoppered, and the yellow solution is boiled for about 1 hour with continuous stirring. During this period the reaction mixture darkens in color and the product separates (Note 3).
The reaction mixture is chilled to about 10° by immersing it in an ice bath for about 30 minutes, and the yellow crystalline precipitate is collected on a Büchner funnel. It is then washed with 100 ml. of cold alcohol and air-dried at room temperature. The yield of 2-mercaptopyrimidine hydrochloride is 71–76 g. (60–64%). The product is pure enough for most purposes (Note 4), but it may be recrystallized by dissolving it in 12N hydrochloric acid (10 ml. per gram of solid) at about 75°, filtering the hot solution through glass wool or a sintered glass filter, chilling the filtrate in ice, and collecting the golden-yellow crystals on a sintered glass filter. Recovery is 60–65% (Note 5).
B. 2-Mercaptopyrimidine. Crude 2-mercaptopyrimidine hydrochloride (25 g., 0.17 mole) is suspended in 50 ml. of water in a beaker and stirred rapidly while a 20% aqueous solution of sodium hydroxide (about 27 ml.) is added until the pH of the mixture is 7–8 (Note 6). The precipitated solid is collected on a Büchner funnel and washed on the funnel with 50 ml. of cold water. The damp product is dissolved by heating it in a mixture of 300 ml. of water and 300 ml. of alcohol on the steam bath, and the hot solution is filtered through a fluted paper and allowed to cool slowly to room temperature. The crystals of 2-mercaptopyrimidine are collected, washed with about 50 ml. of the aqueous alcohol, and dried either at room temperature overnight or for several hours in an oven at 110°. The yield is 15–16 g. (80–85%) of yellow needles, m.p. 218–219° (sealed tube).
2. Notes
1.
Either
commercial absolute alcohol or the 95% grade may be used.
2.
1,1,3,3-Tetraethoxypropane is available from Kay-Fries Chemicals, Inc., New York 16, New York, or from Distillation Products Industries, Rochester 3, New York, and may be used without further purification.
3.
Longer boiling does not affect the yield but causes the product to be somewhat dark-colored. A shorter heating period or lack of mechanical stirring decreases the yield.
4.
Electrometric titration shows the purity to be at least 95%. The product does not melt below 300°.
5.
If concentrated
sulfuric acid is substituted for the
hydrochloric acid in the procedure,
2-mercaptopyrimidine bisulfate is obtained in about
50% yield. Recrystallization from aqueous
acetic acid provides the bisulfate as yellow needles, m.p.
186–186.5°. (
Anal. Calcd. for C
4H
6N
2O
4S
2: C, 22.9; H, 2.9. Found: C, 23.1; H, 2.9.)
6.
pH indicator paper may be used, or the solution may be made weakly basic to litmus. Excess base dissolves the product and should be avoided.
3. Discussion
The synthesis of 2-substituted pyrimidines from 1,3-dicarbonyl compounds and
urea derivatives was first described by Evans
2 and was later improved by Hunt, McOmie, and Sayer
3 for the preparation of
2-mercapto-4,6-dimethylpyrimidine. Burness
4 employed
3-ketobutyraldehyde acetal in this procedure to give
2-mercapto-4-methylpyrimidine.
2-Mercaptopyrimidine has been prepared from
1,1,3,3-tetraethoxypropane and
thiourea by variations of this basic method
3,5,6 as well as by the reaction of
2-chloropyrimidine with
thiourea7 or
sodium hydrosulfide.
84. Merits of the Preparation
This preparation describes a convenient and general method of synthesis of substituted pyrimidines from compounds containing a β-dicarbonyl group, either intact or as the corresponding ketal. The usefulness of the
2-mercaptopyrimidines is enhanced by the ease of removal of the mercapto group by desulfurization
9 or oxidation
10 and its replacement by other functional groups.
10
Appendix
Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)
1,1,3,3-tetraethyoxypropane
2-mercaptopyrimidines
ethyl alcohol,
alcohol (64-17-5)
sulfuric acid (7664-93-9)
hydrochloric acid (7647-01-0)
acetic acid (64-19-7)
sodium hydroxide (1310-73-2)
urea (57-13-6)
thiourea (62-56-6)
sodium hydrosulfide
2-Chloropyrimidine (1722-12-9)
2-Mercaptopyrimidine,
2-Pyrimidinethiol (1450-85-7)
2-mercaptopyrimidine hydrochloride
1,1,3,3-Tetraethoxypropane (122-31-6)
2-mercaptopyrimidine bisulfate
2-mercapto-4,6-dimethylpyrimidine (22325-27-5)
3-ketobutyraldehyde acetal
2-mercapto-4-methylpyrimidine
Copyright © 1921-, Organic Syntheses, Inc. All Rights Reserved