Reactivity of 2-Halo-2H-azirines
J . Org. Chem., Vol. 67, No. 1, 2002 71
Eth yl 3-p h en ylqu in oxa lin e-2-ca r boxyla te (10a ): yield
13.4, 47.7, 57.8, 63.1, 89.4, 127.1, 128.2, 130.0, 136.2, 161.3,
169.5; MS (EI) m/z 249 (M , 4), 176 (10), 103 (100), 77 (12).
6%; mp 51-52 °C (lit.12 mp 51-53 °C); H NMR (CDCl
1
, 300
+
8
3
MHz) δ 1.18 (3 H, t, J ) 7.1 Hz), 4.34 (2H, q, J ) 7.2 Hz),
.50-7.53 (3H, m, Ph H), 7.72-7.76 (2H, m, Ph H), 7.80-7.90
2H, m, Ar H, H-6 and H-7), 8.18-8.25 (2H, m, Ar H, H-5 and
H-8) [assignment of the aromatic protons made on the basis
Eth yl 2-Am in o-3-p h en yl-5,6-d ih yd r o-2H-[1,4]oxa zin e-
2-ca r boxyla te (20). The 2H-azirine 1a (0.467 g, 1.74 mmol)
was dissolved in DMF (10 mL), and ethanolamine (0.8 g, 13.01
mmol) was added. The reaction mixture was agitated in an
ultrasound bath for 3 h. The solvent was evaporated, and the
residue was dissolved in dichloromethane. The solution was
7
(
1
1
13
of a COSY ( H, H) spectrum]; C NMR (CDCl
3
, 75.5 MHz) δ
1
1
1
3.7 (CH CH ), 62.4 (CH CH ), 128.6 (CH, Ph), 128.7 (CH, Ph),
29.4 and 129.6 (CH, C-5 and C-8), 129.6 (CH, Ph), 130.6 and
31.7 (CH, C-6 and C-7), 137.8 (C), 139.9 (C), 142.3 (C), 145.8
2 3 2 3
washed with water (2 × 20 mL) and dried (MgSO
4
). The
solvent was evaporated, giving 20 (0.254 g, 59%) as a solid:
1
(
CdN), 152.3 (CdN), 166.6 (CO
2
Et) [assignment made on the
mp 69-71 °C; H NMR (CDCl
3
, 300 MHz) δ 1.04 (3H, t, J )
1
13
+
basis of a COSY ( H, C) spectrum]; MS (EI) m/z 278 (M ,
9), 249 (27), 206 (100), 77 (23); HRMS (CI) m/z 279.1141
7.1 Hz), 2.59 (2H, br s), 3.94 (4H, br s), 4.11-4.21 (2H, m),
1
3
2
(
7.33-7.37 (3H, m, Ar H), 7.88-7.91 (2H, m, Ar H); C NMR
(CDCl , 75.5 MHz) δ 13.6, 48.1, 57.6, 62.3, 82.5, 127.6, 128.1,
17 2 3
29.9, 136.4, 163.1, 168.9; HRMS (CI) m/z 249.1241 (C13H N O ,
+
C
17
H
15
N
2
O
2
, [M + H] , 279.1133).
3
1
Meth yl 3-ben zoylqu in oxalin e-2-car boxylate (10b): yield
+
1
[M + H] , 249.1239).
7
3%; mp 98-100 °C; H NMR (CDCl , 300 MHz) δ 3.98 (3H,
3
Cr ysta llogr a p h ic Da ta . The X-ray data were collected on
an Enraf-Nonius CAD-4 single-crystal diffractometer, at 298-
(3) K, using graphite-monochromated Mo KR radiation (λ )
s), 7.49-7.54 (2H, m, Ar H), 7.63-7.67 (1H, m, Ar H), 7.95-
.99 (4H, m, Ar H), 8.19-8.22 (1H, m, Ar H), 8.33-8.36 (1H,
m, Ar H); C NMR (CDCl
30.3, 130.4, 132.1, 132.9, 134.0, 135.3, 141.0, 141.4, 143.0,
52.2, 164.8, 192.4; MS (EI) m/z 292 (M , 13), 233 (39), 105
7
1
3
3
, 75.5 MHz) δ 53.5, 128.7, 129.7,
0
.71073 Å). Intensities were recorded as full profiles of ω-2θ
1
1
(
+
scans. The structures were solved by direct methods as
implemented in SHELXS97 and refined by full-matrix least-
squares using SHELXL97. Examination of the structure with
PLATON16 confirmed the absence of voids in the crystal
structures which might be occupied by solvent molecules.
1
4
+
13 2 3
100), 77 (46); HRMS (CI) m/z 293.0925 (C17H N O , [M + H] ,
1
5
2
93.0926).
Dim eth yl qu in oxa lin e-2,3-d ica r boxyla te (10c): yield
9%; mp 132-133 °C (lit.13 mp 132-133 °C); H NMR (CDCl
1
6
3
(
1
1
+
3
,
Cr ysta l d a ta for 7: C13
dimensions 0.34 × 0.24 × 0.10 mm , monoclinic, P2
9.6956(11) Å, b ) 8.727(3) Å, c ) 15.2982(10) Å, R ) 90°, â )
H N O , M ) 232.28, crystal
16 2 2
00 MHz) δ 4.10 (3 H, s), 7.94-7.97 (2 H, m, Ar H), 8.26-8.29
3
1
3
1
/c, a )
3
2 H, m, Ar H); C NMR (CDCl , 75.5 MHz) δ 53.6, 129.9,
+
32.7, 141.5, 143.9, 165.2; MS (EI) m/z 246 (M , 23), 216 (27),
30 (100), 102 (65); HRMS (CI) m/z 247.0715 (C12 , [M
3
9
3.840(10)°, γ ) 90°, V ) 1291.5(5) Å , Z ) 4, Fcalcd ) 1.195 g
3
11 2 4
H N O
-
-1
+
cm , µ ) 0.082 mm , 2441 reflections measured, 2299
independent, R ) 0.046 (1570 reflections with I > 2σ(I), R
.136 for all reflections, GOF ) 1.037, 186 parameters, non-H
atoms refined anisotropically, H atoms refined as riding,
H] , 247.0718).
w
)
Meth yl 2-m eth ylqu in oxa lin e-3-ca r boxyla te (10d ): yield
0
1
8
0%; mp 82-84 °C (lit.12 mp 79-80 °C); H NMR (CDCl
3
, 300
MHz) δ 2.98 (3 H, s), 4.08 (3 H, s), 7.74-7.78 (1 H, m, Ar H),
-3
residual density +0.26/-0.20 e Å
.
7
8
5
1
1
.81-7.85 (1H, m, Ar H), 8.05-8.07 (1 H, m, Ar H), 8.17-
.20 (1H, m, Ar H); 13C NMR (CDCl
, 75.5 MHz) δ 23.8 (Me),
3.2 (CO Me), 128.6 and 129.9 (CH, C-5 and C-8), 129.9 and
31.9 (CH, C-6 and C-7), 139.9 (C), 142.8 (C), 143.9 (CdN),
53.2 (CdN), 166.0 (CO Me) [assignment made on the basis
Cr ysta l d a ta for 14:
C
22
H
21NO
7
, M ) 411.40, crystal
/n, a )
3
3
dimensions 0.39 × 0.27 × 0.12 mm , monoclinic, P2
1
2
1
9
3.219(2) Å, b ) 9.2485(14) Å, c ) 17.148(4) Å, R ) 90°, â )
3
0.54(2)°, γ ) 90°, V ) 2096.3(7) Å , Z ) 4, Fcalcd ) 1.304 g
2
-3
-1
cm , µ ) 0.098 mm , 3845 reflections measured, 3676
independent, R ) 0.054 (2298 reflections with I > 2σ(I), R
.154 for all reflections, GOF ) 1.183, 274 parameters, one of
1
13
+
of a COSY ( H, C) spectrum]; MS (EI) m/z 202 (M , 45), 144
w
)
(
100), 102 (67), 77 (14), 76 (41); HRMS (CI) m/z 202.0741
0
+
(C
11
H
10
N
2
O
2
, M , 202.0742).
Rea ction of 1a w ith Wa ter . Dieth yl 2-Ben zoyl-5-h y-
d r oxy-4-p h en yl-3-oxa zolin e-2,5-d ica r boxyla t e (14). The
H-azirine 1a (0.52 g, 1.94 mmol) was dissolved in DMF (10
the ethyl groups (atoms C14 and C15) disordered over two
positions with occupancies 0.62(2):0.38(2), non-H atoms refined
anisotropically except for those disordered (C14 and C15),
2
which were refined isotropically, H atoms refined as riding,
mL), and water (60 mg, 3.3 mmol) was added. The reaction
mixture was agitated in an ultrasound bath for 2 days. The
solvent was evaporated, and the residue was subjected to flash
chromatography [with hexanes-ethyl acetate (3:1)], giving 14
-3
residual density +0.32/-0.36 e A
.
Cr ysta l d a ta for 18: C13
H
15NO , M ) 249.26, crystal
4
3
dimensions 0.37 × 0.34 × 0.20 mm , monoclinic, P2
1
/c, a )
1
1
4.155(5) Å, b ) 8.165(2) Å, c ) 11.741(5) Å, R ) 90°, â )
(
0.117 g, 30%) as a solid: mp 100-102 °C (from ethyl ether-
3
09.17(3)°, γ ) 90°, V ) 1281.7(8) Å , Z ) 4, Fcalcd ) 1.292 g
1
hexane); H NMR (CDCl
Hz), 1.11 (3H, t, J ) 7.2 Hz), 1.14 (3H, t, J ) 7.2 Hz), 1.18
(
3
, 300 MHz) δ 0.97 (3H, t, J ) 7.2
-3
-1
cm , µ ) 0.096 mm , 2689 reflections measured, 2238
independent, R ) 0.045 (1016 reflections with I > 2σ(I)), R
0.135 for all reflections, GOF ) 0.986, 165 parameters,
non-H atoms refined anisotropically, H atoms refined as riding,
w
3H, t, J ) 7.2 Hz), 4.05-4.35 (8H, m), 5.08 (1H, br s), 5.21
)
(
1H, br s), 7.39-7.55 (10H, m, Ar H), 7.58-7.62 (2H, m, Ar
1
3
H), 7.96-8.02 (4H, m, Ar H), 8.18-8.26 (4H, m, Ar H);
NMR (CDCl , 75.5 MHz) δ 13.5, 13.7, 62.6, 63.3, 63.5, 63.6,
C
-3
residual density +0.20/-0.20 e Å
.
3
1
1
1
05.2, 105.5, 109.9, 110.2, 128.2, 128.3, 128.4, 128.5, 128.7,
28.8, 129.0, 129.8, 129.9, 132.5, 132.6, 133.6, 133.7, 134.0,
Ack n ow led gm en t. We thank Dr. R. Storr (Univer-
sity of Liverpool, U.K.) for very useful discussions
concerning this project. We thank Dr. Thomas McGrath
65.5, 166.7, 167.3, 167.5, 167.9, 168.1, 188.6, 189.7; MS (CI)
+
m/z 429 [(M + NH
4
) , 4], 412 (37), 307 (56), 290 (100), 208
(Baylor University) for running some of the NMR
7
(21), 105 (11). Anal. Calcd for C22H21NO : C, 64.23; H, 5.14;
spectra. We also thank Chymiotechnon and Funda c¸ a˜ o
para a Ci eˆ ncia e a Tecnologia (Grant POCTI 36137/99)
for financial support.
N, 3.40. Found: C, 63.86; H, 5.25; N, 3.28.
Rea ction s of 1a w ith Eth a n ola m in e. Eth yl 2-Hyd r oxy-
3
-p h en yl-5,6-d ih yd r o-2H-[1,4]oxa zin e-2-ca r boxyla te (18).
The 2H-azirine 1a (0.218 g, 0.81 mmol) was dissolved in DMF
5 mL), and ethanolamine (55 mg, 10% in water, 0.8 mmol)
J O010504V
(
was added. The reaction mixture was stirred at room temper-
ature for 16 h. The solvent was evaporated, and the residue
was subjected to flash chromatography [with hexane-ethyl
acetate (1:2)], giving compound 18 (32 mg, 18%) as a solid.
Alternatively the reaction mixture can be agitated in an
(
12) Hoffman, R. V.; Kim, H.-O.; Wilson, A. L. J . Org. Chem. 1990,
5
5, 2820-2822.
(13) Tamura, Y.; Chun, M. W.; Nishida, H.; Kwon, S.; Ikeda, M.
Chem. Pharm. Bull. 1978, 26, 2866-2873.
14) Sheldrick, G. M. SHELXS97, University of Gottingen, Germany,
997.
(
1
1
ultrasound bath for 4 h, giving compound 18 in 7% yield: mp
(15) Sheldrick, G. M. SHELXL97, University of Gottingen, Germany,
1
7
5-77 °C; H NMR (CDCl
3
, 300 MHz) δ 0.99 (3H, t, J ) 7.1
997.
Hz), 3.95-4.27 (6H, m), 4.52 (1H, s), 7.39-7.44 (3H, m, Ar
H), 7.83-7.86 (2H, m, Ar H); C NMR (CDCl , 75.5 MHz) δ
(16) Spek, A. L. PLATON, University of Utrecht, The Netherlands,
1
3
3
2001.