Displacement thiomethyl group

The early chemistry leading to these derivatives was originally carried out via the 6a-(methylthio) derivative (17) which was prepared by way of a Schiff s base (39). The 6a-thiomethyl group could then be displaced by various nucleophiles giving rise to 6a-methoxy or other 6a-substituted penicillins. A stereo-specific one-step introduction of a methoxy group at C-6 in penicillins provided a simple entry to 6a-methoxy penicillins (40) in yields ranging from 50—62%. 

The sulfur analogue of the Hauser ortho-substitution rearrangement provides access to an arylacet-ic NSAID. Reaction of the aminobenzophenone 176 with ethyl methylthioacetate and tert-butyl hypochlorite gives the intermediate 178. The reaction probably proceeds by way of formation of the S-chlorinated sulfonium derivative 177 displacement on sulfur will lead to the salt 178. Treatment with triethylamine leads initially to the betaine 179. Electrocyelic rearrangement of that transient intermediate leads, after rearomatization, to the homoanthranilic acid 180. Internal ester-amine interchange leads then to indolone 181 [45]. The thiomethyl group is then removed with Raney niekel. Saponifieation of intermediate 182 affords bromfenac (183) [46J. 

Similarly, Cocco and co-workers reported the direct displacement of the thiomethyl group from pyrimidines 52 with hydrazine to produce 53, along with varying amounts of the dihydrazide, a result of the displacement of both the thiomethyl group as well as X (X = alkylamine) <00JHC707>. After optimization, 53 could be produced selectively and then cyclized by heating in butanol to form 54 in excellent yields. 

S-Linked groups. Thiomethyl 43 with hydroxyl amine or hydrazine hydrate affords 45 by displacement of the thiomethyl group (Scheme 8, Section 2.1.1.3 (2006IC1945)). 

Nucleophilic displacement of the thiomethyl group in triazines 30 is described (Scheme 47) [23, 24, 80], This reaction is valuable approach to broad variety of trifluoromethylated triazines. 

Scheme 47 Nucleophilic displacement of the thiomethyl group in triazines 30...

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