Base-Promoted [3+2] Annulation of Carbodiimides with Diazoacetonitrile for Synthesis of 5-Amino-4-cyano-1,2,3-triazoles

Abstract

1,2,3-Triazoles are a privileged class of heterocycles in medicinal and agrochemical science. Here, we describe the base-promoted [3+2] annulation of carbodiimides with diazoacetonitrile. This reaction protocol permits access to a variety of novel 5-amino-4-cyano-1,2,3-triazoles in a regiospecific manner. Further derivatization is exemplified by a skeletal rearrangement and an N-functionalization of triazole products.

Key words

annulation - triazoles - [3+2] annulation - carbodiimides - diazoacetonitrile

Publication History

Received: 30 October 2023

Accepted after revision: 22 November 2023

Accepted Manuscript online:
22 November 2023

Article published online:
03 January 2024

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• 16 5-Amino-1H-1,2,3-triazole-4-carbonitriles 3a–t; General Procedure An oven-dried rubber-capped Schlenk tube equipped with a magnetic stirrer bar was charged with the appropriate carbodiimide 1 (0.40 mmol, 1.0 equiv) and Cs₂CO₃ (130.3 mg, 0.60 mmol, 1.5 equiv). Diazoacetonitrile (2; 53.6 mg, 0.80 mmol, 2.0 equiv) was dissolved in MeCN (2.0 mL) in a 10 mL round-bottomed flask at 0 °C, and the resulting cooled solution was transferred into the Schlenk tube by using a syringe. The resulting mixture was warmed to rt and stirred for 8 h. It was then diluted with EtOAc (10 mL) and filtered to remove the residue. The residue was rinsed with EtOAc(2 × 5 mL), and the filtrate was concentrated under a vacuum. The residue was purified by column chromatography (silica gel). 1-(4-Methoxyphenyl)-5-[(4-methoxyphenyl)amino]-1H-1,2,3-triazole-4-carbonitrile (3b) Purified by chromatography [silica gel, hexane to hexane–EtOAc (5:1)] to give a purple solid; yield: 115.7 mg (90%); mp 98–99 °C. ¹H NMR (600 MHz, CDCl₃): δ = 7.38 (d, J = 8.8 Hz, 2 H), 7.04 (d, J = 8.7 Hz, 2 H), 7.01 (d, J = 8.8 Hz, 2 H), 6.82 (d, J = 8.8 Hz, 2 H), 6.51 (s, 1 H), 3.82 (s, 3 H), 3.73 (s, 3 H). ¹³C NMR (101 MHz, CDCl₃): δ = 161.1, 158.3, 145.9, 130.1, 126.8, 126.2, 125.5, 115.4, 114.7, 112.2, 103.9, 55.9, 55.6. HRMS (ESI): m/z [M + H]⁺ calcd for C₁₇H₁₆N₅O₂ = 322.1304; found: 322.1310.