An Efficient Route to Ethyl 5‐Alkyl‐ (Aryl)‐1H‐1,2,4‐triazole‐3‐carboxylates

Abstract

An efficient general route to the synthesis of 5‐substituted 1H‐1,2,4‐triazole‐3‐carboxylates was developed. N‐acylamidrazones were obtained from carboxylic acid hydrazides and ethyl thiooxamate or ethyl 2‐ethoxy‐2‐iminoacetate hydrochloride and then were reacted with chloroanhydride of the same carboxylic acid. As the next step, diacylamidrazones were cyclized to 5‐substituted 1H‐1,2,4‐triazole‐3‐carboxylates one pot in mild conditions.

5‐Substituted 1,2,4‐Triazole‐3‐Carboxylates and 5‐Substituted Ribavirin Analogs Synthesis

“…Basic Protocol 1 was developed for the synthesis of ribavirin analog nucleobase synthesis of 5‐substituted 1,2,4‐triazole‐3‐carboxylic acids derivatives. We obtained these compounds as precursors for nucleoside chemical synthesis (Chudinov et al., 2016; Chudinov, Matveev, Zhurilo, Prutkov, & Shvets, 2015) and to assess the possibilities of enzymatic synthesis of these nucleoside analogs using nucleoside phosphorylases (Konstantinova et al., 2013). We are also studying these compounds' antiviral and anticancer activity (Grebenkina, Matveev, & Chudinov, 2020).…”

Expanding the chemical space of 3(5)-functionalized 1,2,4-triazoles

“…Among the methods developed to date for the synthesis of alkyl 1,2,4-triazole-3(5)-carboxylates 1 , the cyclization of β-acylamidrazones 2 is the most common one. Primarily, it proceeds via thermal activation (Scheme 1 , i ) 33 – 39 or under either anhydride- ( ii ) 40 or acyl chloride-promoted ( iii ) 41 , 42 conditions. In its turn, the main synthetic precursor 2 can be obtained in several ways such as acylation with chlorides 4 of alkyl 2-hydrazinyl-2-iminoacetates 3 (Scheme 1 , path a ) 38 , 39 and condensation of acyl hydrazides 5 with alkyl 2-alkoxy-2-iminoacetates 6 (path b ), 35 , 37 , 41 , 42 ethyl 2-amino-2-thioxoacetate ( 7 ) (path c ), 33 , 36 , 41 or alkyl 2-(alkylthio)-2-iminoacetates 8 (path d ).…”

“…Primarily, it proceeds via thermal activation (Scheme 1 , i ) 33 – 39 or under either anhydride- ( ii ) 40 or acyl chloride-promoted ( iii ) 41 , 42 conditions. In its turn, the main synthetic precursor 2 can be obtained in several ways such as acylation with chlorides 4 of alkyl 2-hydrazinyl-2-iminoacetates 3 (Scheme 1 , path a ) 38 , 39 and condensation of acyl hydrazides 5 with alkyl 2-alkoxy-2-iminoacetates 6 (path b ), 35 , 37 , 41 , 42 ethyl 2-amino-2-thioxoacetate ( 7 ) (path c ), 33 , 36 , 41 or alkyl 2-(alkylthio)-2-iminoacetates 8 (path d ). 34 Apart from that, 3-substituted alkyl 1,2,4-triazole-5-carboxylates 1 could be synthesized by reaction of acid chlorides with ethyl β- N -Boc-oxalamidrazone 9 (path e ), 43 thermal induced condensation of thioamides 10 with ethyl 2-hydrazinyl-2-oxoacetate ( 11 ) (path f ), 33 alkyl imidothioates 12 with alkyl 2-hydrazinyl-2-iminoacetates 3 (path g ), 44 , 45 as well as diethyl oxalate with carboximidhydrazides 13 (path h ).…”

“…Physical and spectral data were in accordance with the previously reported. 33 , 34 , 37 , 41 , 44 , 48 …”

“…Ethyl 5-( tert -butyl)-1 H -1,2,4-triazole-3-carboxylate (1e) was synthesized from compound 5e (2.9 g). Yield 3.84 g (78%), white powder, mp 193–195°C (mp 184–186°C 41 ). Physical and spectral data were in accordance with the previously reported.…”