Safe cyano(nitro)methylating reagent—Michael addition of cyano-aci-nitroacetate leading to δ-functionalized α-nitronitriles

Abstract

A practical, convenient, and safe cyano(nitro)methylation method was developed, in which cyano-aci-nitroacetate served as a synthetic equivalent of anionic nitroacetonitrile. A control of the single/double Michael additions was achieved, which enabled the synthesis of unsymmetrical double Michael adducts. Moreover, the Michael adducts can be used as precursors of pyridine and naphthyridine frameworks.

Modular Synthesis of Carbon-Substituted Furoxans via Radical Addition Pathway. Useful Tool for Transformation of Aliphatic Carboxylic Acids Based on “Build-and-Scrap” Strategy

“…The following trifluoromethylsulfonylation gave the 4-(triflyloxy)­furoxan, which was converted to α-nitrocyano compound 28 upon treatment with Pd­(PPh 3 ) 4 . Although multiple steps are required, the mild reaction parameters enable access to a nitrocyanomethyl group, a relatively rare functional group in literatures. , Compounds 29 – 31 , a molecule class of isoxazole and isoxazoline with an adjacent oxime moiety, could be synthesized by heating a mixture of 3e and 1,3-dipolarophile, alkyne, and alkene according to the relevant literature . Isoxazole 32 , lacking the oxime group versus 29 , could be generated from the same starting furoxan 3e by changing the solvent .…”

Nitroacetonitrile and Its Synthetic Equivalents

“…1,68 While NAN enacts 1,2-addition to α,β-unsaturated aldehyde 9, dianion 41d (N-methylpyrrolidinium salt) effects conjugate addition (1,4-addition) to various α,β-unsaturated ketones 48 and esters. 69 This reaction affords distinct products depending on the level of steric hindrance in 48; that is, only single addition proceeds in the case of β-substituted enones 48a, whereas double addition proceeds in the case of enone 48b without a substituent at the β-position to afford double adduct 50 (Scheme 21).…”

“…Double adduct 50 can be converted to naphthyridine 52 upon heating with ammonium acetate (Scheme 22). 69 In this reaction, the formation of intermediate bis(enamine) 51 is a likely first step, whereupon the amino group attacks the cyano group, followed by aromatization accompanied by elimination of nitrous acid and ammonia and by air oxidation to afford 52.…”

Nitroacetonitrile as a versatile precursor in energetic materials synthesis

“…34 Nitroacetonitrile's role as a cyano(nitro)methylation agent is invaluable as it alters compounds' structures to allow for the straightforward conversion into target molecules with numerous functional groups. 35,36 This is possible due to the highly reactive nature of the cyano group, which enables conversion to amino, acyl, and other functional groups 37 and the nitro group's capability of converting into an amino or carbonyl group 35 and the active methylene center's ability to form C-C or N-C bonds. 38,39 Nitroacetonitrile is thermodynamically unstable, and a common practice is to maintain reactions in which it serves as a reagent under 50 C (max).…”