A. Bhalla, P. Venugopalan, S. S. Bari
FULL PAPER
IR (KBr): νmax = 1739 (C=O) cm–1. C22H19NOS (345.37): calcd. C
76.49, H 5.54, N 4.05; found C 76.31, H 5.43, N 3.99.
CDCl3): δ = 163.0, 156.7, 142.5, 134.0, 130.1, 129.4, 129.1, 126.5,
119.0, 114.4, 106.7, 79.5, 67.5, 58.5, 55.2 ppm. 13C NMR (DEPT
135) (75.5 MHz, CDCl3): δ = 129.4 (+), 129.1 (+), 126.5 (+), 119.0
(+), 114.4 (+), 79.5 (–), 67.5 (+), 58.5 (+), 55.2 (+) ppm. IR (KBr):
˜
trans-3-Benzylthio-3-chloro-1,4-diphenylazetidin-2-one (2c): Yield
0.350 g (53%), white solid flakes, m.p. 147–148 °C (dec.). 1H NMR
(300 MHz, CDCl3): δ = 7.37–7.06 (m, 15 H, ArH), 5.42 (s, 1 H,
C4-H), 4.29 (d, J = 11.4 Hz, 1 H, CHaHbS), 3.99 (d, J = 11.2 Hz, 1
H, CHaHbS) ppm. 13C NMR (75.5 MHz, CDCl3): δ = 160.3, 136.7,
135.5, 131.5 (2), 129.7, 129.5 (2), 129.3 (2), 128.6 (2), 128.5, 127.9
(2), 127.5 (2), 124.8, 117.8 (2), 113.8, 80.7, 71.5, 34.9 ppm. IR
ν
= 1754 (C=O) cm–1. MS (70eV, EI): m/z: 465 (29) [M]+, 316
˜
max
(100), 211 (65), 196 (55), 189 (24), 167 (26), 161 (22), 149 (9), 128
(31), 118 (68), 90 (46), 77 (24), 45 (48). C19H16INO3S (465.29):
calcd. C 49.05, H 3.46, N 3.01; found: C 48.98, H 3.39, N 2.93.
7-Bromomethylene-2-(4-chlorophenyl)-3-phenyl-5-oxa-8-thia-2-aza-
(KBr): ν
= 1769 (C=O) cm–1. C22H18ClNOS (379.89): calcd. C
˜
spiro[3.4]octan-1-one (6d): Yield 0.037 g (69%), colourless, crystal-
max
1
69.56, H 4.77, N 3.69; found: C 69.45, H 4.68, N 3.62.
line solid, m.p. 142–143 °C (dec.). H NMR (300 MHz, CDCl3): δ
= 7.44–7.19 (m, 9 H, ArH), 5.81 (t, 1 H, BrCH), 5.27 (s, 1 H, C3-
H), 4.93 (dd, J = 2.4, 2.4 Hz, 1 H, CHaHbO), 4.84 (dd, J = 2.7,
2.4 Hz, 1 H, CHaHbO) ppm. 13C NMR (75.5 MHz, CDCl3): δ =
163.5, 138.7, 135.2, 133.6, 130.1, 129.7, 129.4, 129.3, 126.5, 118.9,
106.2, 90.6, 76.2, 67.2 ppm. 13C NMR (DEPT 135) (75.5 MHz,
CDCl3): δ = 129.7 (+), 129.4 (+), 129.3 (+), 126.5 (+), 118.9 (+),
cis-3-Benzylthio-1-(4-methoxyphenyl)-4-phenyl-3-(prop-2-ynyloxy)-
azetidin-2-one (3a): Yield 0.040 g (76%), brownish-yellow oil. 1H
NMR (300 MHz, CDCl3): δ = 7.35–6.69 (m, 14 H, ArH), 5.34 (s,
1 H, C4-H), 4.50 (dd, J = 2.4, 2.4 Hz, 1 H, CHaHbO), 4.22 (dd, J
= 2.7, 2.4 Hz, 1 H, CHaHbO), 3.87 (d, J = 12.2 Hz, 1 H, CHaHbS),
3.71 (s, 3 H, OCH3), 3.69 (d, J = 12.2 Hz, 1 H, CHaHbS), 2.47 (t,
1 H, HCϵ) ppm. 13C NMR (75.5 MHz, CDCl3): δ = 161.2, 156.4,
137.4, 133.1, 130.5, 129.2, 128.9, 128.4, 128.1, 127.0, 119.0, 114.4,
98.2, 79.9, 75.4, 67.7, 55.1, 52.8, 32.4 ppm. 13C NMR (DEPT 135)
(75.5 MHz, CDCl3): δ = 129.2 (+), 128.9 (+), 128.4 (+), 128.1 (+),
127.0 (+), 119.0 (+), 114.4 (+), 79.9 (+), 75.4 (+), 67.7 (+), 55.1
90.6 (+), 76.2 (–), 67.2 (+) ppm. IR (KBr): ν
= 1771 (C=O)
˜
max
cm–1. C18H13BrClNO2S (422.71): calcd. C 51.14, H 3.10, N 3.31;
found: C 51.06, H 3.03, N 3.24.
7α-Bromomethyl-2-(4-methoxyphenyl)-3-phenyl-5-oxa-8-thia-2-aza-
spiro[3.4]octan-1-one (8a): Yield 0.022 g (35%), colourless, crystal-
line solid, m.p. 148–149 °C (dec.). Rf (8a) = 0.40, Rf (4a) = 0.45.
1H NMR (400 MHz, CDCl3): δ = 7.39–6.78 (m, 9 H, ArH), 5.24
(s, 1 H, C3-H), 4.52 (dd, J = 1.8, 1.5 Hz, 1 H, CHαHβO), 4.16–
4.12 (m, 1 H, CHαHβO), 3.80–3.74 (m, 1 H, CHβS), 3.74 (s, 3 H,
OCH3), 3.72 (dd, J = 1.8, 1.5 Hz, 1 H, BrCHαHβ), 3.54–3.52 (m, 1
H, BrCHαHβ) ppm. 13C NMR (100 MHz, CDCl3): δ = 164.3,
156.6, 134.5, 130.1, 129.2, 129.1, 126.8, 119.3, 114.5, 103.5, 75.5,
70.0, 55.5, 50.8, 33.1 ppm. 13C NMR (DEPT 135) (100 MHz,
CDCl3): δ = 129.2 (+), 129.1 (+), 126.8 (+), 119.3 (+), 114.5 (+),
75.5 (–), 70.0 (+), 55.5 (+), 50.8 (+), 33.1 (–) ppm. 13C NMR
(DEPT 90) (100 MHz, CDCl3): δ = 129.2 (+), 129.1 (+), 126.8 (+),
(+), 52.8 (–), 32.4 (–) ppm. IR (CHCl ): ν
= 1760 (C=O) cm–1.
˜
3
max
C26H23NO3S (429.51): calcd. C 72.71, H 5.39, N 3.26; found: C
72.67, H 5.33, N 3.29.
cis-3-Benzylthio-1-(4Ј-methoxyphenyl)-4-phenyl-3-(prop-2-enyloxy)-
azetidin-2-one (4a): Yield 0.044 g (84%), yellowish-white solid, m.p.
70–71 °C (dec.). 1H NMR (300 MHz, CDCl3): δ = 7.31–6.70 (m,
14 H, ArH), 5.92–5.81 (m, 1 H, H2C=CH–), 5.37–5.30 (m, 1 H,
CHaHbO), 5.21–5.17 (m, 1 H, CHaHbO), 5.10 (s, 1 H, C4-H), 4.42–
4.35 (m, 1 H, HbHaC=CH–), 4.26–4.19 (m, 1 H, HbHaC=CH–),
3.88 (d, J = 12.3 Hz, 1 H, CHaHbS), 3.70 (s, 3 H, OCH3), 3.66 (d,
J = 12.3 Hz, 1 H, CHaHbS) ppm. 13C NMR (75.5 MHz, CDCl3):
δ = 162.3, 156.3, 137.2, 133.3, 133.2, 132.6, 130.2, 129.1, 128.9,
128.4, 128.2, 127.9, 127.0, 119.0, 117.8, 114.3, 77.2, 68.0, 66.3, 55.4,
32.2, 28.0 ppm. 13C NMR (DEPT 135) (75.5 MHz, CDCl3): δ =
130.2 (+), 129.1 (+), 128.9 (+), 128.4 (+), 128.2 (+), 127.9 (+), 127.0
(+), 119.0 (+), 117.8 (–), 114.3 (+), 68.0 (+), 66.3 (–), 55.4 (+), 32.2
119.3 (+), 114.5 (+), 70.0 (+), 50.8 (+) ppm. IR (KBr): νmax = 1752
˜
(C=O) cm–1. MS (70eV, EI): m/z: 421 (31), 419 (20) [M]+, 272 (100),
271 (97), 211 (75), 196 (57), 167 (17), 121 (28), 118 (78), 90 (25),
88 (19), 77 (21), 73 (44), 44 (33), 41 (97). C19H18NO3BrS (420.30):
C 54.30, H 4.31, N 3.33; found: C 54.23, H 4.25, N 3.29.
(–), 28.0 (+) ppm. IR (CHCl ): ν
= 1762 (C=O) cm–1
.
˜
3
max
7β-Bromomethyl-2-(4-methoxyphenyl)-3-phenyl-5-oxa-8-thia-2-aza-
spiro[3.4]octan-1-one (9a): Yield 0.020 g (32%), yellow oil. Rf (9a)
= 0.40, Rf (4a) = 0.45. 1H NMR (400 MHz, CDCl3): δ = 7.41–6.77
(m, 9 H, ArH), 5.25 (s, 1 H, C3-H), 4.53 (dd, J = 1.8, 1.5 Hz, 1 H,
CHαHβO), 4.40–4.37 (m, 1 H, CHαHβO), 3.83–3.81 (m, 1 H,
CHαS), 3.75–3.74 (m, 1 H, BrCHαHβ), 3.74 (s, 3 H, OCH3), 3.21
(dd, J = 1.8, 1.5 Hz, 1 H, BrCHαHβ) ppm. 13C NMR (100 MHz,
CDCl3): δ = 164.2, 156.6, 135.1, 130.3, 129.1, 126.6, 119.1, 114.4,
104.0, 74.9, 68.2, 55.2, 49.6, 32.9 ppm. 13C NMR (DEPT 135)
(100 MHz, CDCl3): δ = 129.1 (+), 126.6 (+), 119.1 (+), 114.4 (+),
74.9 (–), 68.2 (+), 55.2 (+), 49.6 (+), 32.9 (–) ppm. IR (CHCl3):
C26H25NO3S (431.53): calcd. C 72.36, H 5.83, N 3.24; found: C
72.27, H 5.79, N 3.21.
Preparation of Spiro-β-lactams 5-13. General Procedure: Iodine/bro-
mine (1.2 mmol) was added at room temperature to a stirred solu-
tion of the cis-3-(prop-2-ynyloxy)-β-lactam 3 or the cis-3-(prop-2-
enyloxy)-β-lactam 4 (1.0 mmol) in dry dichloromethane (10 mL).
The reaction mixture was stirred for 4–7 h, the progress of the reac-
tion being monitored by TLC. After TLC indicated complete con-
sumption of the starting substrate, the reaction mixture was poured
into aqueous 5 % Na2S2O3/5 % Na2S2O5 solution (10 mL) and
stirred until the purplish coloration of iodine/reddish coloration
of bromine dissipated. The aqueous mixture was extracted with
dichloromethane (3×10 mL) and the combined organic layer was
washed with brine (2×5 mL) and dried with anhydrous Na2SO4.
After evaporation of the solvent under vacuum, the residue was
purified by column chromatography on silica gel in hexanes/ethyl
acetate (93:7).
ν
˜
max = 1765 (C=O) cm–1. C19H18BrNO3S (420.30): C 54.30, H 4.31,
N 3.33; found: C 54.19, H 4.22, N 3.24.
7α-Bromo-2-(4-methoxyphenyl)-3-phenyl-5-oxa-9-thia-2-azaspiro-
[3.5]nonan-1-one (10a): Yield 0.010 g (16%), white solid flakes, m.p.
146–147 °C (dec.). Rf (10a) = 0.50, Rf (4a) = 0.45. 1H NMR
(400 MHz, CDCl3): δ = 7.33–6.74 (m, 9 H, ArH), 4.90 (s, 1 H, C3-
H), 4.61 (t, 1 H, CHαHβO), 4.34–4.24 (m, 1 H, BrCHβ), 4.20–4.14
(m, 1 H, CHαHβO), 3.90 (t, 1 H, CHαHβS), 3.72 (s, 3 H, OCH3),
2.98–2.92 (m, 1 H, CHαHβS) ppm. 13C NMR (100 MHz, CDCl3):
7-Iodomethylene-2-(4-methoxyphenyl)-3-phenyl-5-oxa-8-thia-2-aza-
spiro[3.4]octan-1-one (5a): Yield 0.044 g (81%), white solid flakes,
m.p. 128–129 °C (dec.). 1H NMR (300 MHz, CDCl3): δ = 7.25– δ = 162.4, 156.5, 132.0, 130.3, 129.4, 128.6, 127.6, 118.9, 114.5,
6.69 (m, 9 H, ArH), 5.74 (t, 1 H, ICH), 5.23 (s, 1 H, C3-H), 4.79
91.4, 71.1, 67.6, 55.2, 43.0, 32.9 ppm. 13C NMR (DEPT 135)
(dd, J = 2.1, 2.4 Hz, 1 H, CHaHbO), 4.75 (dd, J = 2.4, 2.1 Hz, 1
(100 MHz, CDCl3): δ = 129.4 (+), 128.6 (+), 127.6 (+), 118.9 (+),
H, CHaHbO), 3.73 (s, 3 H, OCH3) ppm. 13C NMR (75.5 MHz, 114.5 (+), 71.1 (–), 67.6 (+), 55.2 (+), 43.0 (+), 32.9 (–) ppm. IR
4948
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Eur. J. Org. Chem. 2006, 4943–4950