Efficient synthesis of (Z)-4-((subst.phenylamino)methylidene)-isoquinoline-1,3(2H,4H)-diones using Eschenmoser coupling reaction

Abstract

Novel synthetic strategy involving the Eschenmoser coupling reaction of 4-bromoisoquinoline-1,3(2H,4H)-diones with substituted thioformanilides, thioacetanilides and thiobenzanilides gave 18 (Z)-4-((subst. phenylamino)-methylidene)isoquinoline-1,3(2H,4H)-diones. The reaction occurs under mild conditions (DMF or MeCN, 25-60 °C) without any base or thiophile and in good yields (43-95 %). Furthermore, for the synthesis of starting thioformanilides carrying basic substituents, a new thioacylation protocol was developed that involves a thioacylating agent formed from CS2 and LiBEt3H.