A Simple One-Pot Method for the Preparation of Allyl Azides from Allyl Alcohols Using Triphosgene: Synthesis of N1-Cinnamyl Azetidin-2-ones

Abstract

A simple and efficient one-pot method for the preparation of allyl azides from allyl alcohols using triphosgene and sodium azide is described. An application of cinnamyl azide for the synthesis of various N1-cinnamyl azetidin-2-ones is also described.

Key words

allyl azides - allyl alcohols - azetidin-2-ones - triphosgene

References

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11

Spectral data for cinnamyl azidoformate: colorless oil. IR (CHCl₃): 2175, 2135, 1730, 1500, 1448, 1236, 966 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 4.88 (d, J = 6.0 Hz, 2 H), 6.25-6.35 (m, 1 H), 6.73 (d, J = 16.0 Hz, 1 H), 7.20-7.45 (m, 5 H).

12

Cinnamyl azide (1) and other allyl azides were found to be stable at r.t. but for safety reason they were stored in the refrigerator. [CAUTION: We did not observe any untoward incidence while working with allyl azides. However, the use of hood and safety shield is recommended, as azides are known for their explosive property].

13

Typical Experimental Procedure for the Preparation of Cinnamyl Azide ( 1): To a stirred solution of triphosgene (1.48 g, 5 mmol) in acetone (20 mL) was added a solution of cinnamyl alcohol (1.34 g, 10 mmol) and Et₃N (1.51 g, 15 mmol) at 0 °C. The reaction mixture was stirred for 20 min and then at r.t. for 3 h. It was cooled to 0 °C and sodium azide (1.30 g, 20 mmol) was added in one portion. It was stirred at this temperature for 1 h and kept at r.t. for 12 h. To the reaction mixture H₂O (20 mL) was added and extracted with Et₂O (3 × 20 mL). The organic layer was washed with brine (20 mL) and dried over anhyd Na₂SO₄. The solvent was removed under reduced pressure at r.t. to get pure cinnamyl azide(1) as yellow oil (1.28 g, 80%). [CAUTION: We did not observe any untoward incidence while working with allyl azides. However, the use of hood and safety shield is recommended, as azides are known for their explosive property.] IR (CHCl₃): 2100, 1492, 1448, 1350, 1236, 968 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 3.96 (d, J = 6.0 Hz, 2 H), 6.15-6.35 (m, 1 H), 6.67 (d, J = 17.0 Hz, 1 H), 7.10-7.55 (m, 5 H). MS: m/z (%) = 159 (15) [M⁺], 130 (57), 117 (100), 104 (74).

14

In these cases, N,N-dimethyl carbamoyl azide was obtained as a by-product, which was arising from the reaction of Et₃N, triphosgene and sodium azide with the loss of ethyl group. This reaction will be studied in detail and results will be communicated in future.

16

Typical Experimental Procedure for the Preparation of N -Cinnamyl Azetidin-2-one ( 4a): To a solution of cinnamyl azide (0.318 g, 2 mmol) in toluene (20 mL) was added triphenylphosphine (0.524 g, 2 mmol) and the reaction mixture was refluxed for 6 h. The reaction mixture was cooled to 0 °C and benzaldehyde (0.212 g, 2 mmol) was added to the reaction mixture. It was stirred at r.t. for 12 h. Solvent was removed under reduced pressure and the residue containing imine 3a and triphenylphosphine oxide was dissolved in dry CH₂Cl₂ (20 mL) and directly used for the next reaction without isolation of the imine 3a since it was found to be unstable.
To the above solution of imine in CH₂Cl₂, Et₃N (0.91 g, 9 mmol) was added and the solution was cooled to -15 °C. A solution of benzyloxyacetyl chloride in CH₂Cl₂ (10 mL) was added slowly with stirring in about 30 min and the reaction mixture was allowed to warm up to r.t. and stirred for 18 h. It was washed with H₂O (20 mL), sat. NaHCO₃ solution (20 mL), brine (10 mL) and dried over anhyd Na₂SO₄. Solvent was removed under reduced pressure and the crude product was purified by column chromatography to get white solid β-lactam 4a in 74% yield. White solid, mp 140-141 °C. IR (CHCl₃): 1751 cm^-1. ¹H NMR (200 MHz, CDCl₃): δ = 3.60 (dd, J = 7.8 and 15.1 Hz, 1 H), 4.18 (d, J = 11.2 Hz, 1 H), 4.25 (d, J = 11.2 Hz, 1 H), 4.34-4.41 (m, 1 H), 4.79 (d, J = 4.4 Hz, 1 H), 4.92 (d, J = 4.4 Hz, 1 H), 5.96-6.11 (m, 1 H), 6.39 (d, J = 15.6 Hz, 1 H). 6.94-7.40 (m, 15 H). ¹³C NMR (125 MHz, CDCl₃): δ = 42.1, 61.6, 72.1, 83.6, 122.1, 126.3, 127.7, 127.8, 128.0, 128.1, 128.3, 128.4, 128.5, 134.2, 136.1, 136.3, 166.7. MS: m/z = 369 (M⁺). Anal. Calcd for C₂₅H₂₃NO₂: C, 81.27; H, 6.27; N, 3.79. Found: C, 81.44; H, 6.33; N, 3.67.