2- Mercapto pyrimidines

Abstract This presentation is a brief review on the resnlts of our work on iodine interaction with thioamides, selenoamides and amides. The thioamides, benzothia-zole-2-thione (BZT) (1), 6-n-propyl-2-thiouracil (PTU) (2), 5-chloro-2-mercap-tobenzothiazole (CMBZT) (3), N-methyl-benzothiazole-2-thione (NMBZT) (4), benzimidazole-2-thione (BZIM) (5), thiazolidine-2-thione (TZD) (6), 2-mercapto-pyridine (PYSH) (7), 2-mercapto-nicotinic acid (MNA) (8), 2-mercapto-benzoic acid (MBA) (9) and 2-mercapto-pyrimidine (PMT) (10) react with producing three type of complexes of formulae [(HL)IJ(l2) (HL= thioamide and n= 0, 1), [(HL) [I3 ] and [(HL-L)]+[l3 ]. The interaction of seleno-amides, derived from, 6-n-propyl-2-thiouracil (RSelJ) (R= Me- (11), Et- (12), n-Pr- (13) and i-Pr- (14)) with I, have also been studied and produced the complexes [(RSeU)IJ of spoke structure. These complexes are stable in non-polar solvents, but they decompose in polar solvents, producing dimeric diselenide compounds or undertake deselenation. 

The coordination abilities of A-heterocyclic thiols such as 2-thiopyridine, HSpy (66a), 2-mercapto-pyrimidine, Hspym (66b), or 2-mercaptothiazoline (67) with rhenium centers has already been described for oxorhenium(V) complexes is Section 5.3.2.3.L It has been outlined that ligands with five-membered rings preferably coordinate as monodentate neutral thiones whereas chelate formation is possible for mercaptopyridine or mercaptopyrimidine. Similar complex formation... 

G. Wagner and F. Suss, Uber Glucoside von 2-Hydroxpyrimidin/Pyrimidon-(2) und 2-Mercapto-pyrimidin/Thiopyrimidon-(2), Pharmazie 23 8 (1968). 

In 1995 Schwarz et al.159 described novel heterocyclic structures able to adsorb selectively immunoglobulins. The structures contained sulfur and nitrogen. Reported ligands were 2-mercapto-pyridine,2-mercapto-pyrimidine, and mercapto-thiazoline. These structures were chemically immobilized on silica and agarose beads using epoxy-activated matrices. Binding capacities for silica based material were about 25 mg of IgG per milliliter of resin, while for agarose beads it was about 18 mg/mL. 

Mercapto pyrimidines 82 were synthesized from acetoacetanilide, dihydroxybenzaldehyde, and thiourea, which were readily alkylated with benzyl chloride to afford 2-benzylthio derivatives 83 (Scheme 32). 83 when reacted with different amines in acetic acid furnished 2-amino derivatives 84 (R = Ar), whereas upon reaction with hydrazine hydrate 83 afforded 2-hydrazinyl derivative 84 (R = NH2), which with different aldehydes gave hydrazones 85 (R = 2-furyl, 2-thienyl). Arylidene thiazolidinone 86 was obtained from 84 with carbon disulfide, monochloroacetic acid, and aryl aldehydes, while 84 with ethyl acetoacetate and different aromatic aldehydes provided pyrazoles 87 (Scheme 32) (10MI9). Such tetrasubstituted pyrimidines act as cyclin-dependent kinase (CDK2) inhibitors. 

The molecular weights of the products were within the range of 10 to 10 Da. The product of triphenylantimony dichloride and 4,6-diamino-2-mercapto pyrimidine has a molecular weight of 5.7 x 10 corresponding to a DP of about 1,200. The product from triphenylantimony dichloride and 4,4-diaminodiphenylsulfon is only oligomeric with a molecular weight of 3 x 10 Da corresponding to a DP of 10. 

Heating 5-amino-4-mercapto pyrimidines (61) with formic acid affords the corresponding thiazolo[5,4d]pyrimidines (62) (Scheme 28) (357, 382, 411, 431). 

Figure 6-11. 1 -H-Benzotriazole, 2,5-bis(N-pyridyl)-1,3,4-oxadiazole, cyclohexylammonium benzoate, benzylsulfonylacetic acid, 2,4-diamino-6-mercapto pyrimidine, hydroxamic acid, 3-phenyl-2-propyn-1-ol, dicyclopentadiene dicarboxylic acid.

Since this procedure can be used to replace any sulfur atom in a molecule by a hydrogen, it is not surprising that it has many synthetic uses. Thioketals are converted to the hydrocarbons providing a good method for the removal of a carbonyl group in neutral medium. 57.167 Unsaturated thioketals are desulfurized over deactivated Raney nickel without saturation of the double bond (Eqn. 20.67). Mercapto pyrimidines have been desulfurized in very good yields and sulfonamides converted to amides. 70 Thioethers can be cleaved in preference to benzyl ethers if deactivated Raney nickel is used. 

Zur Cyclisierung von 2,5-Diamino-4-hydroxy-6-mercapto-pyrimidin mit Brom-cyan s. Lit... 

GjHfBrNjS, 5.Brom-4-mercapto-2- thyl> mercapto-pyrimidin 86,13. 

The 5 -Carboxylic acid derivative of 5-fluorouridine has been described.The glucuronide methyl esters of 2-hydroxy- and 2-mercapto-pyriraidine, and of 4-hydroxy- and 4-mercapto-pyrimidine have been prepared by standard methods using pyrimidinols with appropriate sugar derivatives. 

Spectral data of the thiones [e.g. (17a)] and of the zwitterionic structures [e.g. (17b)l have been calculated. The calculations support the results of experimental u.v. analysis in predictions of the most probable tautomeric structures. In general, the thione form is the predominating one. The relevance of zwitterionic structures or at least of polar thione structures is supported by calculations. Zwitterionic structures seem to be important for 3-mercapto-pyridine, and 5-mercapto-pyrimidine, which for valency reasons cannot be written in classical thione form. Attempts to analyse the... 

---