Domino Addition/N-C Heterocyclization of Azides with Allenyl Magnesium Bromide: Rapid Synthesis of 5-Butynyl-1,2,3-triazoles [1]

Abstract

1,5-Disubstituted 1,2,3-triazoles are formed through a novel domino reaction involving the addition of aromatic azides to an excess of allenylmagnesium bromide with concomitant N-C heterocyclization followed by the addition of another mole of allenylmagnesium species to generate the terminal acetylenic product in moderate to high yields.

allenylmagnesium bromide - azides - 5-but-1,2,3-tri­azoles

References and Notes

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RRL communication No. SCL-6/07.

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In a typical procedure, to a suspension of magnesium turnings (1.6 g, 0.07 mol) in anhyd THF with mercury(II) chloride (10 mg, 0.125 w/w of propargyl bromide) was added propargyl bromide (7.5 mL of an 80 wt% solution in toluene, 0.07 mol) in small portions while stirring the reaction mixture at r.t. (Note: A small crystal of iodine is generally required to promote formation of the Grignard reagent). The mixture was stirred at r.t. for 15 min to give a cloudy light green solution. The allenylmagnesium bromide generated as above was cooled to ambient temperature and to it was added dropwise a solution of p-methoxyphenyl azide (1 g, 0.007 mol) and stirring was continued at ambient temperature for 10 min followed by quenching with an aq NH₄Cl solution (10 mL) and diluting with EtOAc (50 mL). The organic layer was separated and the aqueous layer was extracted with EtOAc (2 × 20 mL). The combined organic layers were dried (anhyd Na₂SO₄) and evaporated under reduced pressure to afford the crude product which was subjected to chromatography (basic aluminum oxide, elution: n-hexane-EtOAc gradient) to afford pure 5-but-3-yn-1-yl-1-(4-methoxyphenyl)-1H-1,2,3-triazole as a brown colored syrupy liquid (1.066 g,70%).
IR: 3293, 2957, 2925, 2855, 1722, 1597, 1546, 1501, 1457, 1253, 1120, 1092, 1069, 917, 765, 693, 650 cm^-1. ¹H NMR (CDCl₃): δ = 2.05 (t, J = 2.5 Hz, 1 H), 2.50 (m, 2 H), 2.90 (t, J = 7.3 Hz, 2 H), 3.92 (s, 3 H), 7.30 (d, J = 8.9 Hz, 2 H), 7.45 (d, J = 8.9 Hz, 2 H ), 7.80 (s, 1 H). ¹³C NMR (500 MHz, CDCl₃): δ = 17.83, 22.97, 55.64, 70.07, 81.81, 114.70, 126.84, 128.79, 132.48, 136.34, 162.51. ESI-MS: m/z = 227 [M⁺], 250 [M + Na]. Anal. Calcd for C₁₃H₁₃N₃O: C, 68.71; H, 5.77; N, 18.49; O, 7.04. Found: C, 68.60; H, 5.81; N, 18.60; O, 6.99.