Medicinal nitro compounds

Abstract

Chapter I of this thesis contains a review of the biological properties of nitro compounds. Included in the discussion are those derivatives which have clinically-useful activity and those of a More experimental nature. Some metabolic transformations of nitro compounds are discussed, and the possibility that the toxicity and mutagenic or carcinogenic activity of these compounds may be initiated by reactive chemical species derived from the nitro group is discussed. The use of infrared spectroscopy as a tool to explore features of the structure of nitro compounds is discussed in Chapter II. The asymmetric and symmetric stretching frequencies of the nitro group in a range of derivatives have been accurately recorded, and the influences of substitution, resonance effects,hydrogen-bonding, dipole moment and solvents examined. The infrared spectra of substituted Q-nitrobenzamides are considerably simplified in the solution phase and it is possible to clearly identify both characteristic absorptions: in the solid phasespectra (KBr) this is not always the case. The infrared spectra of N-methyl-o-nitrobenzamide in chloroform is not modified by the incorporation of the de-oxygenating agent triethylphosphite either when the phosphite is in excess or at elevated temperatures. Under the conditions used no induced polarisation of the nitrogroup was detectable. Photolysis of N-ethyl-o-nitrobenzanilide in ethanol afforded a complex mixture of products, amongst which are included azobenzene-2-carboxylic acid, 2'-hydroxyazobenzene-2-carboxylic acid and O-nitrosobenzoic acid. The same three products were identified in the photolysate of N-methyl-o-nitrobenzanilide. In contrast,no azo compounds were detected following photolysis of 1-(o-nitrobenzoyl)-1,2,3,4-tetrahydroquinoline and only Q-nitrosobenzoic acid was characterised. A mechanism to account for the formation of the aforementioned products is included in Chapter III.The N-oxidation of the hypnotic drug methaqualone has been examined (Chapter IV). Methaqualone-N-oxide proved to be a very elusive compound and a satisfactory synthesis was not achieved: the main oxidation product was 2-nitrobenz-o-toluidide. Contrary to previously published reports 2-nitrobenz-otoluidide could not be detected as a human urinary metabolite of methaqualone.