On the reduction of 1-aryl-2-oxo-1,2,3,6-tetra-hydro[1,4]diazepino[6,5-b]indole 4-oxides

Abstract

Electrochemical reduction of 1 aryl 2 oxo 1,2,3,6 tetrahydro[1,4]diazepino [6,5 b]indole 4 oxides, 2 oxo 1 phenyl 1,2,3,6 tetrahydro[1,4]diazepino [6,5 b]indole, and 2 oxo 1 phenyl 1,2,3,4,5,6 hexahydro[1,4]diazepino [6,5 b]indole was studied. The results obtained were com pared with previous data for the reduction of 4 oxides with formamidinesulfinic acid. Key words: [1,4]diazepino[6,5 b]indole 4 oxide, formamidinesulfinic acid, electrochemi cal reduction. Recently, 1,2 we have developed a new approach to the synthesis of [1,4]diazepino[6,5 b]indole 4 oxides and studied their reduction with various agents, including formamidinesulfinic acid.Both tetra and hexahydrodiazepinoindoles can be ob tained, depending on the reducing agent. Reduction of cyclic nitrones such as [1,4]diazepino[6,5 b]indole 4 oxides 1 with formamidinesulfinic acid (used for the first time for this purpose) afforded mixtures of tetra hydro (2) and hexahydro[1,4]diazepino[6,5 b]indoles (3) (Scheme 1). It was found that the para substituents R in the phenyl group bound to the N(1) atom noticeably af fect the reaction outcome, although they are very distant from the reactive site. It was demonstrated 1,2 that the reduction of the N(4)=C(5) bond is favored by electron withdrawing substituents but prevented by electron do nating ones. The significant role of the substituent was attributed to the known positive bridging effect 3,4 charac teristic of compounds with two aromatic fragments (here, benzene and indole) bridged by an O, S, or N atom (as in our case). Such aromatic fragments have the tendency toward efficient p-π conjugation. 3,4The reality of this effect in a system containing a 3 aryl aminoindole fragment was proved by our 1 H NMR study 5 of deuterium exchange in 1 acetyl 3 arylaminoindoles (4a,b). The deuterium exchange rate was higher for com pound 4b (R = 4 Cl): its 1 H NMR spectrum recorded in CD 3 COOD immediately upon the dissolution showed no sig nal for the indole C(2)H pro ton. The slower deuterium ex change in indole 4a than in 4b is probably due to the elec tron withdrawing effect of the NO 2 group, which weakens the electron donating effect of the exo NH fragment.Thus, the para substituent R in the phenyl group af fects the electron density at position 2 of the indole sys tem even in 3 arylaminoindoles and we do not find it surprising that this effect extends to the C=N bond at position 2 of the indole fragment in diazepinoindoles 1.The goal of the present work was to compare the re sults obtained by chemical (with formamidinesulfinic acid) and electrochemical reduction of diazepinoindoles 1.The redox properties of N oxides of aromatic hetero cycles, tertiary amines, and azomethine derivatives have been documented. 6,7 The effect of the nature of the sub stituent on the half wave potential (E 1/2 ) of the reduction Scheme 1 R = 4 NO 2 (a), Cl (b)