Cyanothioacetamide: a polyfunctional reagent with broad synthetic utility

Abstract

The review integrates and analyzes the published data on the chemical reactivity of α-cyanothioacetamide, a convenient starting compound for the preparation of activated alkenes, functionally substituted pyrans, thiopyrans, pyridines, thiophenes, pyrroles, quinolines, isoquinolines, pyrimidines, thienopyrroles, pyrazolopyridines, pyridothienopyrimidines and pyrimidothienodiazines. The relatively small α-cyanothioacetamide molecule has several reaction centres. Nucleophilic reactions of the methylene group are covered most extensively, including the Thorpe reaction; reactions with diazonium salts, azides, iso(thio)cyanates and nitroso compounds; nucleopilic substitution; Knoevenagel condensation; Michael reaction; and multicomponent syntheses. Separate parts of the review are devoted to nucleophilic reactions involving the thiocarbonyl and amino groups and electrophilic reactions involving thiocarbonyl and nitrile groups. The focus is on the publications of the last 15 years. The bibliography includes 350 references.

The Aminometylation of 4-(Alkylthio)-6-amino-2-oxo(thioxo)-1,2-dihydropyridine-3,5-dicarbonitriles

“…Earlier we reported [4][5][6] the aminomethylation reaction of 6-amino-3,5,-dicyano-2-thioxo(oxo)-1,2-dihydropyridines leading to pyrido [1,2-a We prepared ketenedithioacetals 1 from carbon disulfide and malononitrile by known method [3]. Next, the reaction of the prepared ketendithioacetals 1 with active methylene compoundscyanoacetamide [7][8][9] or cyanothioacetamide [7,10] was performed. The reaction was carried out in i-PrOH in the presence of sodium isopropylate, followed by acidification with hydrochloric acid.…”

A Base‐Controlled Reaction of 2‐Cyanoacetamidines (3,3‐Diaminoacrylonitriles) with Sulfonyl Azides as a Route to Nonaromatic 4‐Methylene‐1,2,3‐triazole‐5‐imines

“…Based on the 1 H– 13 C 2D NMR spectra of 11 we identified the signals of C 4 and C 5 of 1,2,3‐triazole ring at 117–119.5 and 146.1–147.7 ppm, respectively. They are different from those for aromatic 5‐sulfonamido‐1,2,3‐triazole which contain both signals in a narrow range of 131.6–139 ppm,[14a] allowing to exclude the tautomer form A from consideration.…”

“…We propose that the triazenyl anion I1 generated by the addition of sulfonyl azide 2 to the carbanion formed after deprotonation of 1 is a common intermediate of the pathways leading to products 3–14 . The cyclization of anion I1 onto the cyano group leading to triazolidine I2 (route a ), and 1,4‐prototropic shift in I1 leading to diazo compound I6 (route b ) are competitive reactions. Cyclization of diazoimines I6 via heteroelectrocyclic ring closure occurs to give final triazoles 3 .…”

“…It is worth noting that in contrast to the well‐studied 2‐cyanothioacetamides,[11a], the chemistry of their aza analogs, 2‐cyanoacetamidines is poorly described in the literature and their reactions with azides presented in only one report. [15e] It was shown there that the formation of intermediate diazo compounds took place as a result of diazo group transfer (Regitz reaction), which then cyclized to 5‐amino‐1,2,3‐triazole‐4‐carbonitriles (Scheme ).…”

Synthesis of new 2-oxonicotinic acids

“…2-Oxo-1,2-dihydropyridine-3-carboxylic acids are less studied; however, they are of interest as complexing agents [5,6] and as pharmaceuticals [7]. Earlier we described [8] the method for preparation of 5-cyano-6-mercapto-2-oxo-1,2-dihydropyridine-3-carboxylic acid 1 starting from Meldrum's acid 2 (for reviews see [9][10][11][12][13][14]) and cyanothioacetamide 3 [15,16] (Scheme 1).…”