Patent GB-791656-A (GB)
Title: Improvements in or relating to the preparation of 5-sulphur-substituted uracils
Filed: 1955-04-20
Abstract: The invention comprises 5-sulphur substituted uracils of the formula: <FORM:0791656/IV (b)/1> (wherein W is hydrogen, halogen, XR or SR1; and in which XR X is C:O, C:S, or C:NH and R is alkyl, aryl or amino, or a substituted derivative thereof; and in which SR1, R1 is an alkyl, aryl or uracil radical or a substituted derivative thereof, and wherein R2 is hydrogen, alkyl, substituted alkyl or carboxyl radical, and R3 is hydrogen or aralkyl or substituted alkyl group) salts thereof, e.g. where W is a metal, particularly sodium or zinc, and a process for the preparation of 5-sulphur substituted uracils by reacting a 5-diazouracil compound either (a) in a mildly acidic medium with a compound having a sulphur atom contained in an enolisable thiocarbonyl group, or (b) under mildly alkaline conditions with a compound containing at least one ionisable divalent sulphur atom. Specified examples of these reagents are sodium disulphide, potassium ethyl xanthate, mercaptans, thiourea, butanethione and thioacetone.  The process may use as starting materials 5-diazouracils which may bear alkyl or substituted alkyl groups at the 1, 3 and/or 6 positions; e.g. the 6-position may be substituted with methyl and carboxyl radicals, and the 1- and 3-positions may bear methyl and carbohydrate radicals; the 2-thio analogues, e.g. 5-diazo-2-thiouracil, may also be used.  The products may be subsequently interconverted, e.g. by oxidation or reduction processes.  In examples: (1)-(3) 5-aminouracil is diazotized in the presence of thiourea, the pH of the resulting solution adjusted to 5-6 and mixture refluxed with more thiourea, when acidification precipitates 5-uracilyl disulphide (bis-5[2,4-dihydroxypyrimidyl]-disulphide); concentration of the mother liquor gives uracil - 5 - isothiouronium chloride (5-2,4 - dihydroxypyrimidyl]isothiouronium chloride); reduction of the disulphide with alkaline glucose yields 5-mercaptouracil; (4) 5-isothiouronium chloride is hydrolysed with sodium hydroxide to 5-mercaptouracil, which on further treatment gives 5-uracilyldisulphide, also prepared (5), by air-oxidizing 5-mercaptouracil in alkaline or boiling aqueous solution; (6) diazotized, 5-aminouracil is added to alkaline sodium disulphide, the mixture acidified, the resulting precipitate boiled with aqueous sodium carbonate and 5-uracilyl disulphide isolated by acidification purified (7), by Soxhlet extraction with water; (8) 5-uracilyl disulphide is reduced with zinc and acetic acid and (9) with glucose and sodium hydroxide; (10) diazotized 5-aminouracil is added to warm aqueous potassium ethyl xanthate and the mixture treated with glucose and KOH yielding 5-mercaptouracil on acidification; (11) subsequent oxidation with iodine in NaOH and treatment with HCl yields 5-uracilyl disulphide; (13) diazotized 5-amino-orotic acid is treated with alkaline sodium sulphide and then acidified giving 5-mercapto-orotic acid; (14) diazotized 5-amino-6-methyluracil is mixed with potassium ethyl xanthate yielding 5-(6-methyluracilyl) ethyl xanthate, which (15), is refluxed with aqueous NaOH yielding 5-mercapto-6-methyluracil; (18) 5-uracilyl disulphide in nitrobenzene is chlorinated to give uracil-5-sulphur chloride; (19) 5-mercaptouracil in hot water is treated with aqueous zinc chloride, when the zinc salt of 5-mercaptouracil precipitates. S-Acetyl-5-mercaptouracil is also mentioned.