Synthesis of 8-Demethyl-8-Formyl Protoporphyrin IX and 8-Demethyl Protoporphyrin IX

SAMBROTTA LUIS; REZZANO IRENE; BUDAIN GRACIELA; FRYDMAN BENJAMIN

TETRAHEDRON

PERGAMON-ELSEVIER SCIENCE LTD

Lugar: Amsterdam; Año: 1989 vol. 45 p. 6645 - 6652

0040-4020

A 8-demethyl-8-formyl-2,4-bis(β-chloroethyl) porphyrin and its 8-demethyl derivative were obtained from the oxidative cyclization of 2,4-bis (β-chloroethyl)-6-(β-ethoxycarbonylethyl)-7-(β-methoxycarbonylethyl)-1′,1,3,5,8-pentamethyl a,c-biladiene dihydrobromide with copper (II) chloride in dimethyl formamide (DMF) in the presence of iodine and air. Under these reaction conditions the cyclization took place at 25°C and the formylporphyrin was obtained in 25% yield together with the C-8 unsubstituted porphyrin which was obtained in 50% yield. The latter could also be obtained in 65% yield by the oxidative cyclization with copper (II) chloride in DMF at 25°C of the β-unsubstituted 1,7-bis (β-chloroethyl)-4-(β-methoxycarbonylethyl)-5-(β-ethoxycarbonylethyl)-1′,2,6,8,8′-pentamethyl-a,c-biladiene dihydrobromide. The formylation attempts at the C-8 unsubstituted position of this porphyrin were however unsuccesful, when either N,N-diisobutyl formamide (Vilsmeier-Haak reaction) or dichloromethyl methyl ether (Friedel Crafts reaction) were used. The title porphyrins were obtained from the aforementioned 2,4-bis(β-chloroethyl) porphyrins by vinylation of the latter with base. 8-Demethyl-8-formyl protoporhyrin IX is a valuable intermediate to probe into the biosynthesis of heme a.