Methylthio groups, nucleophilic substitution

Alkylthio groups are replaced in nucleophilic substitutions. Such reactions are easy in cationic derivatives for example, in the 1,2-dithiolylium series (539), substituted cydopen-tadienyl ion gives fulvene derivatives (540) (66AHC(7)39). 2-Methylthio groups in... 

Nucleophilic displacement of the methylthio group of 3 with hydrazine hydrate was carried out using ethanol as the solvent to afford 2-hydrazino-3-substituted quinazolin4(3H)-one 2 (yield 81%, m.p 158-160 C). 

A simple route to unsymmetrically substituted 1,2,4,5-tetrazines is the reaction of triethyl orthoformate (or acetate), or DMFDMA, with S-methylisothiocarbonohydrazide salt (9) in the presence of triethylamine and air. The use of iminium chlorides (10) gives similar products. The methylthio group can be readily displaced by nucleophiles to give other substituted tetrazines [94JOC8284],... 

Methylthio groups in thiazolylium cations are readily substituted by nucleophilic car-banions generated in the medium, this reaction being used in a classical synthesis of merocyanines dyes (Scheme 151). 

Nucleophilic substitution occurs readily in either ring. The bromine at C-3 in the thiazole (113) is substituted by a methoxy group (73CJC1741), and in the uracil derivative (114) it is a 3-methylthio substituent which is replaced by an amino nucleophile (79H(12)485). Aminoly-sis in an activated azine position proceeds in the usual manner as shown for the 6-chloride (115) (70GEP1950990). 

Alkylthio groups are sometimes replaced in nucleophilic substitutions, but such reactions are difficult in most neutral azoles. Thus, 3-alkylthio-l,2,4-thiadiazoles resist the action of aniline at 100C, ammonia at 120C, molten urea, and ammonium acetate. However, hydrazine attacks 3-methylthio-l,2,4-thiadiazole forming 3-amino-l,2,4-triazole 757. 

S-Orthoesters seldom appear in organic synthesis but they do occupy one useful niche. In 1967 Seebach245-246 introduced tris(methylthio)methyhithium as an acyl anion equivalent of a carboxyl group. It was sufficiently stable and nucleophilic to react with a range of electrophiles. For example, nucleophilic substitution of the allylic chloride 121,1, followed by mercury(Il)-mediated hydrolysis of the SS-orthoester intermediate 121,2, gives the p,y-unsaturated car-... 

A rather complex mixture of products, i.e., 99, 100, 93, and 94, was obtained in the reaction of 3-methylthio-6-chloro-l,2,4-triazin-5-carboxa-mide (98) with ammonia (Scheme 60) (85JHC1329). It has been established that either of the nucleofugic groups in 98 are replaced by ammonia to form the 1,2,4-triazines 99 and 100 (Scheme 60). Substitution of the methylthio group at C-3 generates the nucleophilic methylthio anion, which causes a conversion of unreacted 98 into 3,6-dimethylthio-l,2,4-triazine 101. The latter undergoes subsequent reaction with ammonia to produce both isomeric SN products 93 and 94 (Scheme 60, see also Scheme 58). 

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