Secondary Amine/Nitric Oxide Complex Ions, R2N-. O-Functionalization Chemistry

Article abstract of DOI:10.1021/jo00049a017

Alkylation of the R2N^- anion has been studied with the aim of extending the reaction's scope, probing its stereochemistry, and exploring the reactivity of its variously functionalized products.Using the sodium salt of the R = Et ion (1) as the standard starting material, numerous novel products having the structure Et2NR'(2) were isolated from its reaction with alkyl halides, sulfate esters, and oxiranes.In addition to previously described examples in which R' is a simple straight-chain alkyl or benzyl group, new compound types in which R' is hydroxylated, halide-containing, α-methoxylated, and olefinic were prepared.The 2-bromoethyl derivative could be dehydrohalogenated to the O-vinyl compound or further reacted with other nucleophiles such as amines, water, or a second mole of 1 to produce additonal new compound types.Ethylation of 1 appeared to occur exclusively at the terminal oxygen to give Et2NN(O)=NOEt as the only isomer detected; this conclusion regarding the regiochemistry of the reaction conflicts with that found in the previous literature, but its generality was supported by X-ray crystallographic analysis of the Et2NN(O)=NOCH2CH2(NC5H5)⁺Br^- analogue.Hydrolytic decomposition of 2 was slow, even for the O-vinyl and -methoxymethyl derivatives, as reflected in the sluggish loss of the intense chromophore these compounds characteristically show at 225-245 nm (ε (6.5-9) x 10³ M^-1 cm^-1); half-lives at 37 deg C for the latter two compounds were 12 h in 0.1 M HCl and 9 h in 1 M HCl, respectively.N-Nitrosodiethylamine was a frequent byproduct of both the synthesis and hydrolysis of 2.The results should aid the effort to design prodrug derivatives of 1, a compound type which has recently been shown to exhibit useful pharmacological effects.