Synthesis and physical organic chemistry of C-nitroso compounds: A study of C-nitroso ketones as selective nitrosonium donors

Aliphatic C-nitroso compounds derived from 1,3-diones function as NO donors by formal transfer of a nitrosonium (NO+) equivalent to a simple thiol. The polar mechanism proceeds by NO transfer from the monomeric form of 1(CH3C(NO)(COCH3)2). Transnitrosation is not rate limiting. Rather, the overall kinetics of NO transfer from these compounds are characterized by rate limiting dissociation from the dimer. Phenyl substituted C-nitrosoketones of the form XC6H4C(NO)(COCH3)2 were considered for studies regarding substituent effects on the kinetics and thermodynamics of dimer-monomer interchange as well as on kinetics of transnitrosation, however calculations at the CBS-QB3 level predict the C-N bond dissociation energies in these compounds to be prohibitively low to allow such studies. Interposition of a methylene group between the benzene ring and the nitroso-bearing carbon gave C-nitroso compounds 5 of the form XC6H 4CH2C(NO)(COCH3)2 for which calculations predict an increase in the C-N bond dissociation energies of 5--6 kcal mol-1 over the phenyl substituted diones. While a clear substituent effect on the dissociation kinetics of dimers 5a--e was observed (rho = 0.346, r2 = 0.998), these molecules decomposed in a solvent dependent manner thus compromising their NO donating potential. The decomposition was not expected in C-nitroso monoketones however all attempts to isolate C-nitroso ketone 13a were unsuccessful: rearrangement and decomposition products were isolated in all cases. C-nitrosoketones of the form XC6H4COC(NO)(CH 3)2 15a--h dissociate to the monomers without rearrangement; conjugation of the carbonyl group with the aromatic ring suppresses oxime ester formation. Nitrosonium transfer from these compounds to 1-heptanethiol is rate limiting however in the case of 15h, substituted with a sulfonyl group, dimer dissociation is rate limiting. A linear correlation was observed between the rate of NO transfer and the Hammett substituent constant for compounds 15a--h (rho = 0.591, r2 = 0.999). The sign and magnitude of the Hammett reactivity constant supports the assertion that transnitrosation proceeds by a polar mechanism. The rates of transnitrosation from 15a--h correlate linearly with the equilibrium acidities of compounds 16a--h. Thus, we have demonstrated that the rate of NO transfer from a carbon acid is inversely proportional to the pKa of the parent carbon acid.;We considered C-nitroso sulfones would also serve as NO donors by transnitrosation to thiols. The sulfonyl group was presumed to be insufficiently electrophilic to allow decomposition via intramolecular rearrangement observed in C nitroso ketones. Unfortunately, all attempts to isolate alpha-nitrososulfones were unsuccessful. Instead, the main products isolated from each nitrosation reaction were oximes. From these observations we concluded that monomeric nitrososulfones decompose via 1,3 C→O sulfonyl migration. To our knowledge this is the first report of such a rearrangement in nitrososulfones.