DABCO/AcOH Jointly Accelerated Copper(I)-Catalysed Cycloaddition of Azides and Alkynes on Water at Room Temperature

Abstract

An expeditious room temperature protocol for the synthesis of 1,4-disubstituted 1,2,3-triazoles from terminal alkynes and substituted azides has been achieved using the combination of CuSO₄-ascorbate/1,4-diazabicyclo[2.2.2]octane/acetic acid. This expeditious protocol is applicable to aryl, alkyl, and sulfonyl azides. Acetic acid accelerates the protonation of cuprated triazole and thus avoids the possible side reactions. Devoid of acetic acid, the reaction pathway alters to the ketinimine route and results in the formation of sulfonamides.

Key words

CuAAC - DABCO - alkynes - azides - 1,4-disubstituted 1,2,3-triazole

• References and Notes

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• 16 2-Phenyl-N-tosylacetamide (4a) A mixture of CuSO₄·5H₂O (0.03 mmol), sodium ascorbate (0.12 mmol), and DABCO (0.06 mmol) in H₂O (2 mL) was stirred vigorously at r.t. for 5 min. Alkyne 1a (1 mmol) and p-toluenesulfonyl azide (2j, 1 mmol) were added sequentially, and the resultant mixture was stirred until the substrates had been completely consumed (TLC monitoring). The reaction mixture was diluted by adding EtOAc (5 mL) and aq NH₄Cl solution (3 mL), the mixture was stirred for an additional 30 min, and the two layers were separated. The aqueous layer was extracted with EtOAc (2 × 5 mL), the combined organic layers were dried over Na₂SO₄, filtered, and evaporated. The crude product so obtained was purified by recrystallization from EtOH to afford pure 2-phenyl-N-tosylacetamide (4a) as a white solid; yield 0.095 g, 64%; mp 148–149 °C. ¹H NMR (500 MHz, CDCl₃): δ = 7.87 (d, 2 H), 7.81 (br s, 1 H), 7.33 (m, 5 H), 7.14 (d, 2 H) 3.58 (s, 2 H), 2.44 (s, 3 H).