Synthesis and reactions of 4,6,7,8-tetrahydro-5(1H)-cinnolinones

Abstract

Phenacyldimedone, acetonyldimedone and analogues of general structure 1 undergo reaction with hydrazine, alkylhydrazine and phenyl- and 4-nitrophenyl-hydrazines to form 4,6,7,8-tetrahydro-5(1H)-cinnolinones (2) while lb and 2,4-dinitrophenylhydrazine afford the perhydroindole 4b. Tetrahydrocinnolinones 2a, 2e and 2f yield the partially aromatised oximes 7a-c, while the keto acid 13 gives the decarboxylated oxime 14 or the acylnitrone 15. 1-Aminoalkyl- and 1-alkylcinnolinones (2b-d and 2g) form the same oxime 7a with concomitant loss of the 1-substituent presumably through a quaternary salt of the type 9.1,3-Diphenylcinnolinone 2b is transformed under identical conditions to the quaternary salt 10a in addition to two other products 11 and 12. The oximes 7a-c, 14 and the nitrone 15 on treatment with PPA do not yield the ring enlarged Beckmann products, but undergo Semmler-Wolff aromatisation to afford 5-aminocinnolines (19a-d and 20). Compound 19a is also formed from 7a with cone, sulphuric acid or pyridine-phosphorous oxychloride and from 7,8-dihydro-5(1H)-cinnolinone (16) by a Schmidt reaction. Structures 19a-d have been established by deaminating 19c to known 3-phenylcinnoline and by the formation of pyrazolocinnoline 22 from the diazotisation of 19b. While a number of interesting products are obtained from the oxime 7a with a variety of acidic reagents, only phosphorous pentachloride transforms it to the expected pyridazinoazepinone 30. The study has led to a number of unexpected reactions which have been rationalised.