| A cyclic ketene acetal is an olefin that is substituted at one end by two electron-donating hetero atoms, like O, N, S, where these heteroatoms are connected together by a chain. Delocalization of the lone pair electrons of the two hetero atoms to the double bond makes the beta-carbon (the exocyclic methylene carbon) electron rich and nucleophilic. A major goal of cyclic ketene acetal chemistry is to provide functionalized cyclic ketene acetal monomers as precursors to polymers of desired properties.;The cyclic ketene-N,O-acetal 3-methyl-2-methylene-oxazolidine, generated in situ from 2-methyl-2-oxazolinium iodide and triethylamine, reacted with aryl isocyanates in refluxing THF to give alpha,alpha-bis( N-arylamido) lactams via the iodide-catalyzed rearrangement of beta,beta--bis( N-arylamido) cyclic ketene-N,O-acetal intermediates. However, similar beta,beta--bis(N-arylamido) cyclic ketene-N,O-acetals having two methyl substituents at C-4, did not rearrange due to hindrance of the iodide attack on C-5.;3,4,4-Trimethyl-2-methylene-oxazolidine reacted with aryl chloroformates to form both mono- and di-aryloxycarbonylation adducts. The two methyl groups at C-4 hindered the alternative polymerization route. 3-Methyl-2-methylene-oxazolidine, which does not have two methyl groups at C-4, underwent cationic polymerization under identical conditions.;Benzoylation of 2-methyl-2-oxazoline with benzoyl chloride gave a ring-opened N,C,O-trisbenzoylation product via O-benzoylation of the N,C-bisbenzoylated intermediate, followed by chloride attack on C-5. The N,C,O-trisbenzoylated product underwent N,O-double debenzoylation by KOH to give the cyclic ketene- N,O-acetal, 2-oxazolidin-2-ylidene-1-phenylethanone. This compound (an ambident nucleophile), upon deprotonation, reacted with benzoyl chloride to give the beta,beta-bisbenzoylated cyclic ketene-N,O-acetal, and reacted with phenyl chloroformate to give a novel heterocycle, [1,3]oxazine-2,4-dione. The benzoylation of 2-methyl-2-oxazine gave a similar ring-opened N,C,O-trisbenzoylation product.;Reactions of 2-methyl-2-oxazoline, 2,4,4-trimethyl-2-oxazoline and 2-methyl-2-thiazoline with trifluoroacetyl anhydride gave C-trifluoroacetylated cyclic ketene-N,O(S)-acetals. However, trifluoroacetylation of 2-methyl-2-oxazine gave the beta,beta-bistrifluoroacetylated cyclic ketene-N,O-acetal.;In summary, a novel iodide-catalyzed rearrangement of beta,beta--bis( N-arylamido)-cyclic ketene-N,O-acetals was found. The [1,3]oxazine-2,4-dione heterocycle synthesized during this research also demonstrates the synthetic potential of cyclic ketene acetal chemistry in pharmaceutical industry. Functionalization of cyclic ketene acetals based on the chemistry developed in this work will find applications in polymer industry. |
