CONJUGATE ADDITION TO ACTIVATED BETA-ARYLACRYLIC ACID DERIVATIVES . THIOLATE ANIONS

The reactions of N-β-(3-indol)acryloylimidazole (1) with N,N-dimethylcysteamine and cysteamine have been investigated. Data are presented and interpreted as compelling evidence for the conjugate addition of thiolate anions to form transient intermediates which undergo a second nucleophilic attack at the carbonyl carbon by a second molecule of thiolate anion, and then, via β elimination, the corresponding β-(3-indol)acryloyl thiolester is formed. When N,N-dimethylcysteamine is the reacting thiol, the final products are the thiolester, S-β-(3-indol)-acryloyl-N,N-dimethylcysteamine, in equilibrium with the corresponding conjugate addition product. When cysteamine is the reacting thiol, the conjugated amide, N-β-(3-indol)acryloylcysteamine, obtains in yields which are pH dependent, although the S to N rearrangement of the thiolester under the same conditions is found to be quantitative. Pathways for these reactions are discussed, and a rationale is offered to explain the observation of conjugate addition by these sulfur nucleophiles vis-á-vis carbonyl attack by oxygen and nitrogen nucleophiles. © 1969, American Chemical Society. All rights reserved.