An Azido-Hanessian Reaction

Abstract

Benzal acetals have been found to react with iodine azide to provide 2-azidoethyl- or 3-azidopropyl benzoates.

azide - azidonation - radicals - proctection group conversion

References

1a Hanessian S. Carbohydr. Res.  1966,  2:  86 

1b Hanessian S. Plessas NR. J. Org. Chem.  1969,  34:  1035 

1c Failla DL. Hullar TL. Siskin SB. Chem Commun.  1966,  716 

1d Hullar TL. Siskin SB. J. Org. Chem.  1970,  35:  225 

2a Keck GE. Lundquist GD. J. Org. Chem.  1999,  64:  4482 

2b Liu D. Chen R. Hong L. Sofia MJ. Tetrahedron Lett.  1998,  39:  4951 

2c Reddy VD. Franck RW. J. Org. Chem.  1993,  58:  6911 

2d Santoyo Gonzalez F. VargasBerenguel A. Hernandez Mateo F. Garcia Mendoza P. Baer HH. Carbohydr. Res.  1992,  237:  145 

2e Baer HH. Hernandez Mateo F. Siemsen L. Carbohydr. Res.  1990,  195:  225 

3a Glass BD. Goosen A. McCleland CW. J. Chem. Soc., Perkin Trans. 2  1993,  2175 

3b Hai-xia L. Liang-heng X. Nai-ju H. Synth. Commun.  1997,  27:  303 

3c Talekar DG. Joshi PL. Ramaiah P. Rao AS. Indian J. Chem., Sect. B  1986,  25:  145 

4

IN₃ is a potentially explosive compound. We have never encountered any problems, but it is advisable to destroy the reagent after the reaction using Na₂S₂O₃ wash.

5 Viuf C. Bols M. Angew. Chem. Int. Ed.  2001,  40:  623 

6 The 1-monodeuterated analogue of 5 has been reported: Hammerschmidt F. Liebigs Ann. Chem.  1988,  955 

7

A typical reaction to prepare 5 was carried out as follows: To a stirred solution of NaN₃ (107 mg, 1.4 mmol) in dry CH₃CN (3 mL) at -10 °C was added a dry solution of iodine monochloride (101 mg, 0.6 mmol) in CH₃CN (2 mL) through a syringe under nitrogen atmosphere. After stirring 20 min the cooling bath was removed, and 2-phenyl-1,3-dioxolane (45 mg, 0.3 mmol) was added. The mixture was refluxed for 45 min. Upon completion (monitored by TLC), the reaction mixture was cooled to r.t., then CH₂Cl₂ (25 mL) was added, and the solution was washed with 5% Na₂S₂O₃ solution (20 mL). The dried (Na₂SO₄) organic phase was concentrated in vacuo, and the residue was purified by flash chromatography (silica gel, pentane-EtOAc 10:1, R_f = 0.58) to give 2-azidoethyl benzoate 5 (44 mg, 78%) as a colourless oil.

8

Spectral data for 5 (ref. [4] ): ¹H NMR (200 MHz, CDCl₃): δ = 3.61 (t, J = 5 Hz, 2 H, CH₂N), 4.45 (t, J = 5 Hz, 2 H, CH₂O), 7.40-7.52 (m, 3 H, Ar), 8.10 (m, 2 H, Ar); ¹³C NMR (50 MHz, CDCl₃): δ = 50.1 (CH₂N), 63.8 (CH₂O), 128.6, 129.9, 133.4 (Ar), 166.4 (COO); MS (ES): 214.1 [M + Na⁺]. For 7: ¹H NMR: δ = 1.40 (d, J = 6.5 Hz, 3 H, CH₃), 3.38 (dd, J = 6.1, 12.9 Hz, 1 H, HCHN), 3.43 (dd, J = 3.8, 12.9 Hz, 1 H, HCHN), 5.25 (m, 1 H, CHO), 7.50 (m, 3H, Ar), 8.10 (m, 2 H, Ar); ¹³C NMR: δ = 17.6 (CH₃), 55.2 (CH₂N), 70.3 (CH₂O), 128.5, 129.8, 133.3 (Ar), 166.6 (COO); MS (ES): 228.1 [M + Na⁺]. For 8 (ref. [8] ): ¹H NMR: δ = 1.24 (d, J = 6.5 Hz, 3 H, CH₃), 3.82 (m, 1 H, CHN), 4.20 (dd, J = 3.8, 11.4 Hz, 1 H, HCHO), 4.30 (dd, J = 7.4, 11.4 Hz, 1 H, HCHO), 7.50 (m, 3 H, Ar), 8.10 (m, 2 H, Ar). For 10: ¹H NMR: δ = 2.10 (p, 2 H, CH₂), 3.40 (t, J = 7 Hz, 2 H, CH₂N), 4.36 (t, J = 6.3 Hz, 2 H, CH₂O), 7.30-7.60 (m, 3 H, Ar), 8.10 (m, 2 H, Ar). ¹³C NMR: δ = 28.4 (CH₂), 48.4 (CH₂N), 62.0 (CH₂N), 128.6, 129.7, 133.2 (Ar), 166.2 (COO); MS (ES): 228.0 [M + Na⁺]. For 12: ¹H NMR: δ = 2.10 (m, 2 H, CH₂), 3.40 (t, J = 7 Hz, 2 H, CH₂N), 3.80 (s, 3 H, OMe), 4.27 (t, J = 6.3, 2 H, CH₂O), 6.82 (m, 2 H, Ar), 7.90 (m, 2 H, Ar); MS (ES): 258.05 [M + Na⁺]. For 14: ¹H NMR: δ = 3.64 (t, J = 5.1 Hz, 2 H, CH₂N), 4.50 (t, J = 5 Hz, 2 H, CH₂O), 8.20-8.40 (m, 4 H, Ar). ¹³C NMR: δ = 49.9 (CH₂N), 64.6 (CH₂O), 123.8, 127.6, 131.1 (Ar), 164.5 (COO).

9 Bartels B. Hunter R. J. Org. Chem.  1993,  58:  6756 

10 Compound 8 is known: Ariza X. Urpi F. Viladomat C. Vilarrasa J. Tetrahedron Lett.  1998,  39:  9101