We have found O(2)-substituted diazeniumdiolates, compounds of structure R(2)N-N(O)=NOR' that are under development for various possible pharmaceutical uses, to be rather photosensitive. With R = ethyl and R' = methyl, benzyl, or 2-nitrobenzyl, the observed product distributions suggest that two primary pathways are operative. A minor pathway involves the extrusion of nitrous oxide (N(2)O) with simultaneous generation of R(2)N(*) and R'O(*), which may then form amines, aldehydes, and alcohols. The major reaction pathway is an interesting photochemical cleavage of the N=N bond to form a nitrosamine (R(2)NN=O) and an oxygen-substituted nitrene (R'ON). The intermediacy of the O-nitrene was inferred from the production of abundant oxime, via rearrangement of the O-nitrene to a C-nitroso compound (R'ON --> O=NR'), and subsequent tautomerization to the more stable oxime. Involvement of the O-nitrene was confirmed by trapping with 2,3-dimethyl-2-butene to form the aziridine and with oxygen to generate the nitrate ester. 2-Nitro substitution on the benzyl derivative had surprisingly little effect on the reaction course. For each compound examined, minor amounts of nitric oxide (NO), presumably produced by secondary photolysis of the nitrosamine, were observed. Time-resolved infrared experiments provided additional support for the above reaction pathways and confirmed that the nitrosamine is a primary photoproduct. We have also found that the relative contributions of the reaction pathways can be altered in certain derivatives. For example, when R' = 2,4-dinitrophenyl, the contribution of the nitrosamine/O-nitrene-forming pathway was diminished. Pharmacological implications of these results are discussed.

Irradiation of dimethylpyridine vapors (2-5 Torr) at 254 nm results in the formation of two sets of isomerization products. One set, formed in the larger yield, is substantially quenched when the irradiations are carried out in the presence of 15-21 Torr of nitrogen and is not formed when the irradiations are carried out with light of λ > 290 nm. In addition, a second set of reactions, which involve the interconversion of 2,3-and 2,5-dimethylpyridines, is enhanced by the addition of nitrogen, and these reactions are the only photoisomerization reactions observed when the irradiations are carried out with light of λ > 290 nm. In addition to the photoisomerizations, four of the dimethylpyridines also undergo demethylation to yield monomethylpyridines, and 2,6-dimethylpyridine undergoes methylation to yield a trimethylpyridine product. A variety of crossover experiments confirmed that the photoisomerizations are intramolecular. Based on the major phototransposition products, the six dimethylpyridines can be divided into two triads. Interconversion of the three members of each triad results in the major phototransposition products. These intra-triad interconversions are suggested to occur via 2,6-bonding, originating in a vibrationally excited S 2 (π,π*) state of the dimethylpyridine, followed by nitrogen migration and rearomatization. This allows nitrogen to insert within each carbon-carbon bond. Phototransposition of 2,6-dideuterio-3,5-dimethylpyridine to a mixture of 5,6-dideuterio-2,4-dimethylpyridine and 3,4-dideuterio-2,5-dimethylpyridine is consistent with this mechanism. In addition to these intra-triad reactions, 2,5-dimethylpyridine, a member of triad 1, was observed to interconvert with 2,3-dimethylpyridine, a member of triad 2. These inter-triad reactions are suggested to occur via interconverting Dewar pyridine intermediates, formed from the triplet state of the dimethylpyridines. These Dewar pyridine intermediates were also observed by 1 H NMR spectroscopy after irradiation of the dimethylpyridines in CD 3 CN at -30 °C.

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