Synthesis of Diazeniumdiolates from the Reactions of Nitric Oxide with Enolates

Abstract

[reaction: see text] Reactions of nitric oxide with enolates derived from aliphatic methyl ketones containing alpha-methylene or alpha-methine groups and with enolates derived from alpha,alpha'-dimethylene or alpha,alpha'-dimethine ketones yield mono- or bis(diazeniumdiolate) products. Diazeniumdiolation occurs in the following order: alpha-methine > alpha-methylene > alpha-methyl. The amount of the base used alters the extent of diazeniumdiolation and the course of the reaction. Mono- and bis(diazeniumdiolate)-substituted methyl ketones are cleaved in the presence of excess base before and after the subsequent diazeniumdiolation of the alpha-methyl group. Similar to the trihalogenated methyl groups in the base-assisted halogenation reactions of methyl ketones, the bis(diazeniumdiolate)-substituted alpha-methylene and alpha-methyl groups act as leaving groups in the presence of excess base. The reaction of nitric oxide with a (approximately 20:80, cis/trans) mixture of 2,6-cyclohexananone yields the cis and trans isomers of 2,6-dimethylcyclohexanone-2,6-bis(diazeniumdiolate) in 12.9% and 57.6% yield. Single-crystal X-ray diffraction data determined for potassium cis-2,6-dimethylcyclohexanone-2,6-bis(diazeniumdiolate), cis-14b, reveal that the N(2)O(2-) substituent is planar with considerable delocalization of a double bond over the anionic four-atom group. Except for one of the diazeniumdiolate products, namely, potassium propanoate 2,2-bis(diazeniumdiolate), 8b, all are stable in neutral and basic aqueous media. Compound 8b slowly decomposes in neutral aqueous solution releasing nitrous oxide and nitric oxide gases but is stable in basic aqueous media. Differential scanning calorimetry data measured for the diazeniumdiolate products indicate that they decompose exothermally with most of them undergoing explosive decomposition at moderately high temperatures (181-274 degrees C).

1,1′-Dimethoxy-3,3′-dimethyl-3,3′-(hexane-1,6-diyl)bis(triazen-2-ium-2-olate): a nitric oxide donor

“…Within the N 2 O 2 À structure, the N1-N2 and N2-O1 bond distances are short (Table 1), indicating extensive charge and double-bond delocalization. The torsion angle and bond lengths are similar to those in other structurally characterized N-or C-diazeniumdiolates (Keefer et al, 2001;Saavedra et al, 1992Saavedra et al, , 2004Arulsamy et al, 2005Arulsamy et al, , 2006. The substituted methyl group on O2 is believed to reduce the negative character from the planar N(O) NO À group, which prevents protonation, thereby increasing the half-life of the diazeniumdiolate structure under physiological conditions (Saavedra et al, 1992).…”

E/Z Oxime Isomerism in PhC(NOH)CN

“…Under these conditions of base, cation, and higher temperature, methanol adds to the nitrile to give an imidate methyl ester that, when protonated, gives nitrous oxide, nitric oxide, and 4 . In prior work, we have found that the products of diazeniumdiolate reactions are often strongly dependent on the identity of the cation used in the base with sodium and potassium cations often giving surprisingly different products and product distributions 13. The origin of this effect relates to the differing solubilities of the intermediate salts and products during the course of the reaction.…”

Nitric Oxide Catalysis of Diazene E/Z Isomerization

“…Although nitric oxide has complicated reactivity patterns that reflect its accessible redox potentials as well as its electrophilicity, 28,42 we have shown that it is a surprisingly robust cis− trans isomerization catalyst. Previous research into its catalytic quality has focused, understandably, on the gas phase, where nitric oxide is most commonly found in the laboratory and in industry.…”