PAPER
Synthesis of 3-Aryl-2H-azirine-2-carboxaldehydes
51
1H NMR (CDCl3): = 1.90 (t, 1 H, J = 5.0 Hz), 2.38 (s, 3 H), 4.35
(m, 2 H), 5.33 (t, 1 H, J = 6.8 Hz), 7.20–7.23 (m, 2 H), 7.26–7.29
(m, 2 H).
dized in a first step) seems to be mandatory for the
cyclization to take place.
13C NMR (CDCl3): = 21.3, 58.3, 117.6, 127.1, 129.5, 131.6,
139.3, 139.4.
EI-MS: m/z (%) = 161 (M+ – 28, 11), 144 (73), 118 (100).
MnO2
N
CHCl3, rt
Ph
N3
Ph
11a
Anal. Calcd for C10H11N3O (189.22): C, 63.48; H, 5.86; N, 22.21.
Found: C, 63.21; H, 5.77; N, 22.18.
Scheme 4 Treatment of -azidostirene with MnO2
(Z)-3-Azido-3-(4-chlorophenyl)prop-2-en-1-ol (8c)
Yield: 51%; mp 53–56 °C (colorless prisms from n-hexane).
In conclusion, we have developed a new approach to 3-
aryl-2H-azirine-2-carboxaldehydes, highly valuable in- IR (nujol): 3314, 2113, 1645, 1491, 1099, 1014, 964, 844, 726, 641
cm–1.
termediates in organic synthesis, which compares favor-
1H NMR (CDCl3): = 1.86 (br s, 1 H), 4.36 (d, 2 H, J = 6.6 Hz),
5.37 (t, 1 H, J = 6.6 Hz), 7.33 (d, 2 H, J = 8.6 Hz), 7.40 (d, 2 H,
J = 8.6 Hz).
13C NMR (CDCl3): = 58.2, 118.9, 128.5, 129.2, 132.9, 135.4,
138.2.
ably with methods previously reported.
MnO2 was purchased from Aldrich (activated, 5 micron, ca. 85%)
and was dried at 120 °C for 24–48 h before use. Melting points were
taken on a Reichert apparatus and are not corrected. IR spectra were
1
EI-MS: m/z (%) = 211 ([M + 2]+, 2), 209 (M+, 5), 140 (30), 138
recorded on a FT-IR Nicolet Impact 400 IR spectrometer. H and
13C NMR spectra were measured on a Bruker AC 200 (1H: 200
MHz, 13C: 50 MHz) or Varian Unity-300 (1H: 300 MHz, 13C: 75
MHz) spectrometer with TMS ( = 0.00) for the 1H and the CDCl3
residual peak ( = 77.1) for the 13C resonances as internal standards.
Mass spectra were obtained using a Hewlett-Packard 5993C spec-
trometer (electron impact technique, 70 eV) and VG Analytical
AUTOSPEC spectrometer (FAB+ technique with an EBE configu-
ration at a 8kV accelerating voltage, a FAB Cs gun operating at
25kV and 3-nitrobenzyl alcohol as a matrix). Elemental analyses
were performed on a Carlo Erba EA 1108-Elemental analyzer.
(100).
Anal. Calcd for C9H8ClN3O (209.63): C, 51.57; H, 3.85; N, 20.04.
Found: C, 51.42; H, 3.75; N, 20.16.
(Z)-3-Azido-3-(4-bromophenyl)prop-2-en-1-ol (8d)
Yield: 31%; yellow oil.
IR (neat): 3429, 2110, 1648, 1487, 1079, 1015, 959, 831 cm–1.
1H NMR (CDCl3): = 2.09 (br s, 1 H), 4.35 (d, 2 H, J = 6.8 Hz),
5.37 (t, 1 H, J = 6.8 Hz), 7.22–7.29 (m, 2 H), 7.52–7.58 (m, 2 H).
13C NMR (CDCl3): = 58.1, 118.9, 123.5, 128.7, 132.1, 133.3,
138.1.
EI-MS: m/z (%) = 227 ([M + 2]+ – 28, 8), 225 (M+ – 28, 8), 210
(Z)-3-Aryl-3-azidoprop-2-en-1-ols 8; General Procedure
A solution of Br2 (1.62 g, 10.1 mmol) in CH2Cl2 (60 mL) was added
dropwise to a solution of the corresponding cinnamyl alcohol 6
(10.1 mmol) in CH2Cl2 (75 mL) at 0 °C, with stirring under N2, at
the rate that the color of Br2 faded continuously. The addition of Br2
requires about 1 h. The solution was stirred for 20 min more at 0 °C
and then, poured into 150 mL of a 5% aq Na2S2O3 solution. The or-
ganic layer was separated and the aqueous phase was extracted with
EtOAc (3 50 mL). The combined organic layers were dried
(MgSO4), filtered, and then concentrated to give the corresponding
erythro-3-aryl-2,3-dibromopropan-1-ol 7, which was used in the
next step without further purification. Thus, a solution of the dibro-
mide 7 (9.3 mmol) in DMSO (10 mL) was added to a suspension of
NaN3 (0.71 g, 11.0 mmol) in the same solvent (20 mL) at 0 °C under
N2 and stirred for 24 h at r.t. At this time, a solution of NaOH (0.51
g, 12.8 mmol) in H2O (10 mL) was added dropwise to the reaction
mixture at 0 °C and stirred for 92 h at the same temperature. The
mixture was poured into H2O (50 mL) and the organic materials
were extracted with EtOAc (3 50 mL). The combined extracts
were washed with H2O and brine, dried (MgSO4), filtered, and then
concentrated to give a residue, which was purified by column chro-
matography eluting with EtOAc–hexanes, 1:3.
(100), 208 (97).
Anal. Calcd for C9H8BrN3O (254.09): C, 42.54; H, 3.17; N, 16.54.
Found: C, 42.18; H, 3.06; N, 16.68.
3-Aryl-2H-azirine-2-carboxaldehydes 1; General Procedure
MnO2 (2.00 g) was added to a solution of the corresponding (Z)-3-
aryl-3-azidoprop-2-en-1-ol 8 (1.0 mmol) in CHCl3 (15 mL). The re-
action mixture was stirred at r.t. until the total disappearance of the
azidoalcohol 8 (TLC on silica gel plate; EtOAc–hexanes, 1:3) (5–
16 h). The crude product was filtered through a pad of Celite and the
residue was washed with CHCl3 (3 10 mL). The filtrate was con-
centrated to give an oily residue which was further purified by silica
gel chromatography eluting with the appropriate mixture of sol-
vents.
3-Phenyl-2H-azirine-2-carboxaldehyde (1a)6
Eluent: EtOAc–hexanes, 1:3; yield: 55% (16 h reaction time); mp
49–50 °C (Lit.6 mp 49–51 °C).
IR (nujol): 1775, 1704, 1121, 1102, 990, 766, 689 cm–1.
1H NMR (CDCl3): = 2.89 (d, 1 H, J = 6.5 Hz), 7.59–7.71 (m, 3 H),
7.90–7.94 (m, 2 H), 8.97 (d, 1 H, J = 6.5 Hz).
(Z)-3-Azido-3-phenylprop-2-en-1-ol (8a)8
Yield: 57% (Lit.8 57%); yellow oil.
IR (neat): 3327, 2113, 1650, 1492, 1025, 966, 711, 704 cm–1.
1H NMR (CDCl3): = 2.30 (br s, 1 H), 4.35 (d, 2 H, J = 6.7 Hz),
5.36 (t, 1 H, J = 6.7 Hz), 7.35–7.40 (m, 5 H).
13C NMR (CDCl3): = 39.0, 122.6, 129.5, 130.6, 134.5, 159.4,
200.0.
3-(4-Methylphenyl)-2H-azirine-2-carboxaldehyde (1b)
Eluent: Et2O–hexanes, 1:9; yield: 52% (5 h reaction time); mp 31–
32 °C (colorless prisms from Et2O–n-pentane at –40 °C).
(Z)-3-Azido-3-(4-methylphenyl)prop-2-en-1-ol (8b)
Yield: 30%; mp 55–56 °C (colorless prisms from Et2O–n-pentane).
IR (nujol): 1772, 1716, 1111, 1093, 966, 820, 765 cm–1.
IR (nujol): 3224, 2113, 1648, 1507, 1025, 1016, 957, 789, 723, 647
cm–1.
Synthesis 2003, No. 1, 49–52 ISSN 0039-7881 © Thieme Stuttgart · New York