Unexpected products from the reactions of 6-cyano-, and 6-nitro-3.4-epoxy 3,4-dihydro-2,2-dimethyl-2H-1-benzopyran with azacyclotridecanone

✍ Scribed by Frederick Cassidy; John M Evans; Duncan M Smith; Geoffrey Stemp

• Publisher: Elsevier Science
• Year: 1987
• Tongue: French
• Weight: 173 KB
• Volume: 28
• Category: Article
• ISSN: 0040-4039
• DOI: 10.1016/s0040-4039(00)96136-7

✦ Synopsis

The title reactions furnished the pyran ring cleaved product (3) and the tetracyclic chromene (5), rather than the expected 4-cyclicamido-3hydroxy benzopyrans (l,R=CN and NO2, respectively, n=ll). Mechanisms proposed for these reactions require a strong electron withdrawing group at C(6) in the benzopyran, and a conformationally mobile lactam ring. A key step in the synthesis of the novel anti-hypertensive agent BRL 34915 (1, R=CN, n=3)1,2 involves nucleophilic attack by the anion generated from 2-pyrrolidone (NaH, DMSO, room temperature, under N2, 2-6hrs) on the 3,4_epoxybenzopyran (2, R=CN). As part of a study of the effect of lactam ring size on anti-hypertensive activity in this class of compound, we have investigated the reaction of azacyclotridecanone with epoxides (2, R=H, Cl, CN, or NO2) under the same conditions.

For the epoxides (2, R=H, or Cl), the usual products (1, R=H, or Cl, n=ll) were obtained3. However, the major product from epoxide (2, R=CN) was the unexpected 2, 3,4,5,6,7,8,9,10,11,12,13-dodecahydro-17-hydroxy-1-(2-methyl-l-propenyl)-18-oxo-2,13-methano-1H-2-benzazacyclopentadecine-14carbonitrile (3) together with compound (4) as a minor product3. The only product from epoxide (2, R=NO2) was 4,