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Thermal cyclization of a 2-isocyanoacetamide; 5-(1-pyrrolidinyl)oxazole

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Submitted Apr 18, 2020, published Apr 19, 2020
Stephen Habay (sahabay@salisbury.edu), Abhishek Purohit (apurohit1@gulls.salisbury.edu), Jeffrey Benner (jbenner1@gulls.salisbury.edu)
A contribution from Habay Group
Reaction Scheme: Thermal cyclization of a 2-isocyanoacetamide

Chemicals Used

2-isocyano-N-pyrrolidinylacetamide 833

Procedure

Solid 2-isocyano-N-pyrrolidinylacetamide (5.92 g, 42.8 mmol) was added to a dry 25-mL RBF containing a magnetic stir bar. The flask was fitted with a U-shaped vacuum distilling adapter connected to a 25 mL receiving flask (see apparatus setup image). The reaction flask was immersed in an oil bath and heated, under vacuum (0.5 mm Hg), to a bath temperature of 160-165 °C for 20 h. The collected distillate, containing product and trace starting material, was rapidly vacuum distilled (vapor temp of 55-65 °C) into a dry 10-mL RBF to obtain pure 5-(1-pyrrolidinyl)oxazole (2.41 g, 17.4 mmol) as a clear colorless liquid (41 %).

Author's Comments

  • It is important to NOT use a water-cooled condenser for this distillation, as condensate can solidify in the condenser and block the flow of vapor. We experimented with short-path and Kugelrohr-type condensers, but found the U-shaped condenser to work best.
  • All joints were sealed with vacuum grease and a high temperature-compatible heating fluid was used in the oil bath. 
  • The condenser can be insulated with aluminum foil to increase efficiency.
  • The solid starting material begins to melt at a bath temperature of 80 °C, at which point the stir bar will spin freely.
  • The condenser was cleaned and dried prior to the second distillation.

Data

1H-NMR (400 MHz, CDCl3): δ  7.38 (s, 1H), 5.82 (s, 1H), 3.27 (t, 4H), 1.98 (t, 4H) ppm.

Lead Reference

Chupp, J.P.; Leschinsky, K.L. Heterocycles from Substituted Amides. VII (1,2). Oxazoles from 2-Isocyanoacetamides. J. Hetercyclic Chem., 1980, 17, 705-709.

Supplementary Information

1H NMR spectrum (1H NMR spectrum.pdf)
Apparatus image (apparatus image.JPG)

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Get structure file (.cdx, .sk2, .mol)

Keywords: amides, cyclization, heterocyclic compounds, thermal