Reaction of Bromo Dipoles with (Z)-4-(Arylmethylene)azol-5-ones. Substrate-Controlled Synthesis of New Bromo-Substituted Heterocyclic Spirans and Unusual N-Benzoyl α-Aminoacids

Abstract

Bromo spirans 6 and 7 and unusual α-aminoacids 8 were prepared as diastereoisomerically pure compounds from bromo ­dipoles and (Z)-4-arylmethyleneazolones.

dipolar cycloadditions - nitrile oxides - nitrile imines - bromoheterocycles

References

1a Foti F. Grassi G. Risitano F. Tetrahedron Lett.  1999,  40:  2605 

1b Foti F. Grassi G. Risitano F. Helv. Chim. Acta  2001,  84:  3313 

2 Caramella P. Grunanger P. In 1,3-Dipolar Cycloaddition Chemistry   Vol. 1:  Padwa A. Wiley-Interscience; New York: 1984.  Chap. 3.

3

Spyrans 6a-c were synthesized from 4-arylmethylene-imidazolones 1 and bromonitrilimine 4 at r.t. by a route analogous to that previously described in ref. [1]

4

Typical procedure for bromonitrile oxide cycloaddition: To a stirred mixture of EtOAc (50 mL) and NaHCO₃ (4.2 g, 50.0 mmol) was added a solution of 2 or 3 (10 mmol) and dibromoformaldoxime [11] (2.7 g, 13.0 mmol) in THF at r.t. The reaction was stirred for ca. 24 h at r.t. After completion of the reaction, the mixture was filtered and evaporated in vacuo. EtOAc was then added to the residue. The residue was washed twice with brine, dried over Na₂SO₄, and the solvent was removed under vacuum. Column chromatography of the residue on silica gel (CHCl₃) gave the indicated products as colorless crystals.

5a Grassi G. Risitano F. Foti F. Cordaro M. Synlett  2001,  812 

5b Risitano F. Grassi G. Foti F. Bruno G. Rotondo A. Heterocycles  2003,  60:  857 

6 Maquestiau A. Van Haverbeke Y. Muller RN. Tetrahedron Lett.  1972,  1147 

7

Selected data. Compound 6a: mp 114-116 °C. IR (nujol): 1758 cm^-1. ¹H NMR (DMSO-d ₆): δ = 5.06 (s, HC-4). ¹³C NMR (DMSO-d ₆): δ = 67.8 (C-4), 92.3 (C-5). MS (EI):
m/z = 444/446 [M⁺]. Compound 6b: mp 119-121 °C. IR (nujol): 1755 cm^-1. ¹H NMR (DMSO-d ₆): δ = 5.05 (s, HC-4). ¹³C NMR (DMSO-d ₆): δ = 67.3 (C-4), 92.4 (C-5). MS (EI): m/z = 458/460 [M⁺]. Compound 7a: mp 190-191 °C. IR (nujol): 1801, 1747 cm^-1. ¹H NMR (DMSO-d ₆): δ = 5.10 (s, HC-4). ¹³C NMR (DMSO-d ₆): δ = 59.2 (C-4), 96.1 (C-5). MS (EI): m/z = 309/311 [M⁺]. Compound 7b: mp 240-242 °C. IR (nujol): 3336, 1796, 1752 cm^-1. ¹H NMR (DMSO-d ₆): δ = 5.01 (s, HC-4). ¹³C NMR (DMSO-d ₆):
δ = 59.0 (C-4), 95.7 (C-5). MS (EI): m/z 340/342 [M⁺]. Compound 7c: mp 264-265 °C. IR (nujol): 1746 cm^-1. ¹H NMR (DMSO-d ₆): δ = 5.11 (HC-4). ¹³C NMR (DMSO-d ₆):
δ = 59.1 (C-4), 96.2 (C-5). MS (EI): m/z = 344-346 [M⁺]. Compound 8a: mp 128-130 °C. IR (nujol): 3485,1709, 1684 cm^-1. ¹H NMR (DMSO-d ₆): δ = 5.55 (s, HC-4). MS (EI): m/z = 338/390 [M⁺]. Compound 8b: mp 164-165 °C. IR (nujol): 3438, 1713, 1698 cm^-1. ¹H NMR (DMSO-d ₆): δ = 3.61 (s, 3 H), 5.55 (s, HC-4). MS (EI): m/z = 418/420 [M⁺].

8a Levy GC. Lichter RL. In ¹⁵N Nuclear Magnetic Resonance Spectroscopy   John Wiley and Sons; New York: 1979.  Chap. 3. p.28 

8b

¹H NMR, ¹³C NMR, and ¹⁵N NMR spectra were recorded with a Bruker ARX 300 spectrometer at 300.13, 75.47, and 30.41 MHz, respectively. The ¹H NMR spectra were calibrated against the residual proton signal of the solvent (CDCl₃: δ = 7.24 ppm), the ¹³C{¹H} NMR spectra against the triplet of the solvent (CDCl₃: δ = 77.0 ppm), and the ¹⁵N{¹H} NMR spectra against external CH₃NO₂ (1v:1v) in CDCl₃ at δ = 379.60 ppm.

9a Faber K. Kappe T. J. Heterocycl. Chem.  1984,  21:  1881 

9b

Selected data for 9: mp 210-211 °C. IR (nujol): 3398, 3243, 3166, 1734, 1698 cm^-1. ¹H NMR (300 MHz, DMSO-d ₆): δ = 7.47 (s, HC-4), 10.83 (s, 1 H). MS (EI):
m/z = 309/311 [M⁺].

10

X-ray data to be submitted to Acta Cryst.

11 Halling K. Thomsen I. Torssell KBG. Liebigs Ann. Chem.  1989,  985