Name : Timothy Teschler Title : Preparation and Derivatization of Novel Sydnonimines and their Esters Date : August 2007

Some years ago, we reported that 3-phenylsydnone underwent dilithiation to yield the dilithio species, upon treatment with n-butyllithium. Subsequent reactions with electrophiles led to variously substituted aryl sydnones, dependent on the nature of the electrophile employed. Sydnonimines, exocyclic nitrogen analogs of sydnones, exhibit interesting biological properties and, accordingly, it was of value to explore whether or not the dilithiation approach could be extended to such species. In the present work a series of N-6-ethoxycarbonyl-3-arylsydnonimines were synthesized from the corresponding sydnonimine hydrochlorides in moderate yields (22-77%). Attempted dilithiations of N-6-ethoxycarbonyl-3-arylsydnonimines and trapping with iodine proved to be problematic, yielding only the mono substituted (at the 4-position) iodosydnonimine and not the desired disubstituted sydnonimine in a model study with N-6-ethoxycarbonyl-3phenylsydnonimine. The 4-iodo species was extremely unstable, decomposing to the parent sydnonimine on standing or exposure to moisture, however, by careful chromatography, it was possible to isolate the N-6-ethoxycarbonyl-4-iodo-3-phenylsydnonimine in a very low yield (1.6%). Further lithiations with different reagents and substrates led to many unidentified reaction products, none of which appeared to be a sydnonimine. Reactions of N-6-ethoxycarbonyl-3-arylsydnonimines with brominating agents (potassium bromate and N-bromosuccinimide) showed that the preference was for substitution on the sydnonimine ring (yields of the 4-bromo congeners ranged from 32-90%). With the latter, it was discovered that removal of the bromine at the 4-position could be effected cleanly using sodium borohydride. The chlorinating agent potassium chlorate also showed a preference for substitution on the sydnonimine ring, however, other chlorinating agents (N-chlorosuccinimide and (dichloroiodo)benzene) did not effect chlorination on the aryl ring or sydnonimine ring in model studies with N-6-ethoxycarbonyl-3-phenylsydnonimine. Iodinating agents (iodine monochloride, N-iodosuccinimide) did not react with N-6-ethoxycarbonyl-3-phenylsydnonimine in model studies. Sonogashira coupling reactions with N6-ethoxycarbonyl-4-bromo-3-phenylsydnonimine and N-6-ethoxycarbonyl-4-chloro-3-phenylsydnonimine and terminal acetylenes showed that the chlorine at the 4-position could not be exchanged, and the bromine at the 4-position was reduced to the parent sydnonimine.