A Novel Base‐Solvent Controlled Chemoselective Azide Attack on an Ester Group versus Keto in Alkyl 3‐Substituted 3‐Oxopropanoates: Mechanistic Insights

Abstract

During the exploration of arylazides reactions with alkyl 3‐substituted‐3‐oxopropanoates under the Dimroth reaction conditions (MeONa‐MeOH) azide attack on ester group versus keto was found out in few examples yielding stable 3‐alkyl‐2‐diazo‐3‐oxo‐N‐(aryl)propanamides instead of obvious target 1‐aryl‐5‐alkyl‐1H‐1,2,3‐triazole‐4‐carboxylic acids. The formation of diazocompounds was observed in case of 3‐(4,4‐diethoxymethyl)‐, isopropyl‐, cyclopropyl‐3‐oxopropanoate in the reaction with arylazides, especially, those containing electro‐withdrawing substituents. Influence of the base‐solvent system on diazo products yields was investigated and mechanistic insights of Dimroth reaction were discussed.

Synthesis, crystal structure and Hirshfeld surface analysis of N-(4-chlorophenyl)-5-cyclopropyl-1-(4-methoxyphenyl)-1H-1,2,3-triazole-4-carboxamide

“…1, the 4-methoxyphenyl and 1,2,3-triazole rings are turned relative to each other by 87.77 (7) because of a significant steric hindrance of the cyclopropyl ring relative to the 4-methoxyphenyl substituent [the N1-C9-C11-C13 and N1-C9-C11-C12 torsion angles are 41.2 (4) and À31.6 (4) , respectively]. The above angle between the planes is comparable with that for the bulky 5-(2-phenylhydrazineylidene)methyl analogue [73.3 (2) ; Pokhodylo et al, 2018] but is considerably larger than in the structure of 5-cyclopropyl-1-(3-methoxyphenyl)-1H-1,2,3triazole-4-carboxylic acid [39.1 (2) ] in which the cyclopropyl ring is oriented to the triazole ring (Pokhodylo et al, 2017) or in 5-methyl-1-(4-nitrophenyl)-1H-1,2,3-triazol-4-ylphosphon-ate [45.36 (6) ; Pokhodylo et al, 2020]. In selected 5-free triazoles, 1-(3-bromo-or 4-fluorophenyl)-1H-1,2,3-triazol-4yl)methyl methylphosphonates, this angle is 22.9 (3) and 15.7 (2) , respectively (Pokhodylo, Shyyka et al, 2019).…”

“…In addition to the antitumor studies, 1H-1,2,3-triazole-4-carboxamides exhibit other biological activities such as fungicidal (Wang et al, 2014), antiviral (Krajczyk et al, 2014) and antimicrobial (Jadhav et al, 2017) activities and were found to be inhibitors of the Wnt/catenin signalling pathway (Obianom et al, 2019). It should be noted that the diversity of such compounds can be obtained by amidation of 1H-1,2,3-triazole-4-carboxylic acids prepared by convenient Dimroth synthesis and further modifications (Pokhodylo et al, 2009(Pokhodylo et al, , 2017(Pokhodylo et al, , 2018Pokhodylo, Savka et al, 2010;. Given the considerable interest in such scaffolds for drug discovery, a detailed study of their structural features is relevant and the crystal structure of the title compound, C 19 H 17 ClN 4 O 2 , is described herein.…”

4‐Phosphonated or 4‐Free 1,2,3‐Triazoles: What Controls the Dimroth Reaction of Arylazides with 2‐Oxopropylphosphonates?

“…Recently, we reported that K 2 CO 3 /DMSO is a mild base‐solvent system which provides high selectivity in the reaction of azides with α ‐ketomethylenic compounds and eliminates undesired concurrent processes. Therefore, we adopted K 2 CO 3 in DMSO to test a number of arylazides with diverse substituents.…”

Acylation of 1,1-dichloroethylene by the arylalkanoic acid chlorides: synthesis of 4-chloro-2-naphthols

“…Реакції ацилювання 1,1-дихлоретилену хлорангідридами кислот за типом реакції Фріделя-Крафтса є зручним шляхом синтезу β-трихлорометилкетонів та їх похідних -дихлоровінілкетонів. Такі β-хлорокетони є попередниками широковживаних в органічному синтезі біфункціональних реагентів, зокрема, β-кетоестерів [1], β-кетоортоестерів [2,3] та різноманітних гетероциклічних сполук, таких як хлоропіразоли [4][5][6][7], піримідини [8,9], 1,3-оксазини [10], 1,3-тіазини [11,12], бензо-l,3-тіоли [13] тощо. В тактиці органічного синтезу β-хлорокетони розглядають як синтетичні еквіваленти діелектрофільного синтону + С-С-С + і можуть бути використані для введення в молекулу фрагмента =С-С=C-Cl.…”