Mercaptopyrimidine

A. 2-Mercaptopyrimidine hydrochloride. Thiourea (61 g., 0.80 mole) and 600 ml. of ethyl alcohol (Note 1) are placed in a 2-1. 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 Buchner 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. 

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 Buchner 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). 

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-... 

The synthesis of 2-substituted pyrimidines from 1,3-dicarbonyl compounds and urea derivatives was first described by Evans2 and was later improved by Hunt, McOmie, and Sayer3 for the preparation of 2-mercapto-4,6-dimethylpyrimidine. Burness4 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 6 6 as well as by the reaction of 2-chloropyrimidine with thiourea 1 or sodium hydrosulfide.8... 

This preparation describes a convenient and general method of synthesis of substituted pyrimidines from compounds containing a /3-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.1 ... 

Malonic acid, amino-, diethyl ester, HYDROCHLORIDE, 40, 24 Malonic acid, bts(hydroxymethyl)-, DIETHYL ETHER, 40, 27 Malonitrile, condensation with tetra-cyanoethylene, 41, 99 2-Mercaptopyrimidine, 43, 6S hydrochloride of, 43, 68 Mercuric oxide in preparation of bromo-cyclopropane, 43, 9 Mesityl isocyanide, 41,103 5-Methallyl-l,2,3,4,5-pentachlorocyclo-pentadiene, 43, 92 Methane, dimesityl-, 43, 57 Methanesiileinyl chloride, 40, 62 Methanesulfonic acid, solvent for making peroxybenzoic acid from benzoic acid, 43, 93... 

Tetraethoxypropane, condensation with thiourea to give 2-mercaptopyrimidine, 43,68... 

Bare Ag electrodes. It is noteworthy that the recently studied electrode processes of organic compounds at pc-Ag electrodes involve mainly biochemically important species. For example, Zeng et al. [278] have investigated the voltammetric behavior of 2-mercaptopyrimidine (MPD) and have found that at appropriate potentials, MPD adsorbs on and interacts with the electrode to form an insoluble silver salt at the surface. The first of two cathodic... 

Hdmmpd = N,N -dimethyl-N,N -bis(2-mercaptoethyl)propylenediamine. b Hmpr = 2-mercaptopyrimidine. c nane = 1,4,7-triazacydononane. 

Cosimelli B, Greco G, Ehlardo M, Novellino E, Da Settimo F, Taliani S, La Motta C, Bellandi M, Tuccinardi T, Martinelli A, Ciampi O, Trincavelli ML (2008) Martini C (2008) derivatives of 4-Amino-6-hydroxy-2-mercaptopyrimidine as novel, potent, and selective A3 adenosine receptor antagonists. J Med Chem 51 1764-1770... 

For the particular case of 2- and 4-mercaptopyridines and 2-mercaptopyrimidines and by means of absorption UV-VIS spectroscopy, Stoyanov and collaborators122 have shown that polar solvents shift the thiol/thione tautomerism towards the thione form, while in dilute solutions of nonpolar solvents the thiol form predominates. However, one of the most significant contributions of this work122 is the observation of self-association. It also favors the thione forms and is followed by quantitative transformation of the thiol form into the corresponding symmetrical disulfides (see Scheme 6). More importantly thione-disulfide process is reversible in water, which can be of some relevance in biological systems. 

HYDROXYLAMINE see HLiMSOO HYDROXYLAMINE NEUTRAL SULFATE see OLSOOO HYDROXYLAAONE SULFATE see OLSOOO HYDROXYLAMINE SULFATE (2 1) see OLSOOO HYDROXYUYWONIUM SULFATE see OLSOOO HYDROXYLATED LECITHIN see HLN700 6-HYDROXY-2-MERCAPTOPYRIMIDINE see TFR250... 

For example, when 2-mercaptopyrimidine and dimethylformamide dimethyl acetal are refluxed for 1 hr. in benzene, 2-methylthiopyrimidine is obtained in 86% yield. 

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