Ritter Reactions. I. Combined Intramolecular Cyclization and Amide Formation

Abstract

1,5-Dimethylenecyclooctane (5) and 7,11-dimethylene-6,7,8,9-tetrahydro-5,9-propano-5H-benzocycloheptene (7) undergo efficient intramolecular cyclization and Ritter reaction in a one-flask procedure. Similarly,11-methylene-5,6,8,9-tetrahydro-5,9-propano-7H-benzocyclohepten-7-one (10) may be converted into cyclic hydroxy amide products. Alternatively, a combined intramolecular cyclization and double Ritter reaction with acetonitrile can be carried out to produce 7,9-bis( acetamido )-6,7,8,9,10,11-hexahydro-5,9:7,11-dimethano-5H-benzocyclononene monohydrate (12) whose crystal structure (C₁₉ H₂₄ N₂ O₂ H₂O,P2₁/ca = 10.477(l), b = 14.595(1), c = 14.493(l) Å, β =127.900(3)º, Z= 4) was determined with a final R = 0.039. Hydrogen-bonded dimeric units of the bis(amide) are surrounded by six water molecules which are involved in three different hydrogen-bonded arrangements. Mixed bis(amide) products may also be produced from (10) via the hydroxy amide, demonstrating that the bis(amide)(12) results from sequential Ritter reactions.