1-(4-Nitrophenyl)-1H-1,2,3-Triazole-4-carbaldehyde: Scalable Synthesis and Its Use in the Preparation of 1-Alkyl-4-Formyl-1,2,3-triazoles

Abstract

1,2,3-Triazole-4-carbaldehydes are useful synthetic intermediates which may play an important role in the discovery of novel applications of the 1,2,3-triazole moiety. In this work, a one-step multigram scale synthesis of 4-formyl-1-(4-nitrophenyl)-1H-1,2,3-triazole (FNPT) as a preferred reagent for the synthesis of 1-alkyl-4-formyltriazoles is described, making use of the commercially available 3-dimethylaminoacrolein and 4-nitrophenyl azide. Next, the earlier reported reaction of FNPT with alkylamines is further explored, and for hexylamine, the one-pot sequential cycloaddition and Cornforth rearrangement is demonstrated. In addition, a useful protocol for the in situ diazotization of 4-nitroaniline is provided. This facilitated the complete hydrolysis of rearranged 4-iminomethyl-1,2,3-triazoles and allowed for the recycling of 4-nitrophenyl azide.

New Thienobenzo/Naphtho-Triazoles as Butyrylcholinesterase Inhibitors: Design, Synthesis and Computational Study

“…New naphtho-triazoles 1 and 2 and thienobenzo-triazoles 3 – 6 were prepared by photocyclization from the corresponding triazolo-stilbenes 1a and 2a and triazolo-thienostilbenes 3a – 6a ( Scheme 1 ). Triazolo-stilbenes 1a and 2a and triazolo-thienostilbenes 3a – 6a , as mixtures of cis - and trans -isomers, were prepared by the Wittig reaction according to the described procedure in moderate to good yields (45–60%) [ 21 , 24 ] and transformed to the new naphtho-triazoles 1 and 2 and thienobenzo-triazoles 3 – 6 as new biological targets ( Scheme 1 ). The Wittig reactions were performed with aryl- and 2-thienyl-phosphonium salts in absolute EtOH, sodium ethoxide, and different triazole aldehydes.…”

New Heterostilbene and Triazole Oximes as Potential CNS-Active and Cholinesterase-Targeted Therapeutics

“…Triazole oximes 1-3 were obtained (in 8-50% of isolated yields) from the triazole nitro aldehyde 24 (Scheme 1) either by direct conversion into an oxime (compound 3) or by conversion of nitro aldehyde in a reaction with amine into new substituted triazole aldehydes 22 and 23, and then by their conversion into an oxime (compounds 1 and 2). This synthesis involves the corresponding starting amines in reaction with triazole nitro aldehyde 24 [18,19] to produce new triazole aldehydes 22, 23 and 25 (see Experimental Section) as starting substrates for the Wittig reaction. Scheme 1.…”

Cholinesterase Inhibitory and Anti-Inflammatory Activity of the Naphtho- and Thienobenzo-Triazole Photoproducts: Experimental and Computational Study

“…New triazolo-stilbenes 1a-7a and triazolo-thienostilbenes 8a-13a (Scheme 1) were prepared by the Wittig reaction from phosphonium bromide and the 1-substituted-1,2,3triazole-4-carbaldehydes, according to the previously described procedure [26]. Wittig reaction provided the new triazolo-stilbenes 1a-7a and triazolo-thienostilbenes 8a-13a as mixtures of cis-and trans-isomers (isolated yields on the mixtures were 42-78%, Scheme 1) which were not separated in this research into pure geometrical isomers but immediately converted into photoproducts, naphtho-triazoles 1-7 and thienobenzo-triazoles 8-13 (Scheme 1) as new biological targets by an intramolecular electrocyclization reaction in high isolated yields (29-60%, Scheme 1).…”

“…Tested thienobenzo-triazoles (14)(15)(16)(17)(18)(19)(20)(21)(22), their non-aromatic analogs (23)(24)(25)(26), and thienobenzo-thiazoles (27)(28)(29)(30)(31) for cholinesterase inhibition [27] and anti-inflammatory activity.…”

“…While the naphthotriazoles did not affect cell viability, for the most potent thienobenzo-triazoles 19, 20, and 26, cell viability reduction was observed at the highest tested concentration. (14)(15)(16)(17)(18)(19)(20)(21)(22), their non-aromatic analogs (23)(24)(25)(26), and thienobenzothiazoles (27)(28)(29)(30)(31) for cholinesterase inhibition [27] and anti-inflammatory activity. Since previously studied thienobenzo/naphtho-triazoles displayed activity toward cholinesterase inhibition, further functionalization and examination of these core units were imposed.…”