Supporting Information
Highly stereoselective synthesis of new aziridines via Baldwin rearrangement
and their potential biological activities
Bhaskar Chakraborty*, Manjit Singh Chhetri & Esmita Chhetri
Organic Chemistry Laboratory, Sikkim Government College, Gangtok, Sikkim-737102, India
E-mail: bhaskargtk@yahoo.com
EXPERIMENTAL
1
H NMR spectra were recorded with a Bruker DRX 300 spectrometer (300 MHz, FT NMR) using TMS as
internal standard.
13
C NMR spectra were recorded on the same instrument at 75 MHz. The coupling
constants (J) are given in Hz. IR spectra were obtained with a Perkin-Elmer RX 1-881 machine as film or as
KBr pellets for all the products. MS spectra were recorded with a Jeol SX-102 (FAB) instrument. All the
reactions were monitored by TLC using 0.25 mm silica gel plates (Merck 60F254 UV indicator) while
column chromatography was performed with silica gel (E.Merck India) 60–200 mesh. All other reagents
and solvents were purified after receiving from commercial suppliers. N-methylhydroxylamine, Nbenzylhydroxylamine were purchased from Aldrich Chemical Company and were used as received. Nphenylhydroxylamine and N-cyclohexylhydroxylamine were prepared following standard methods
available in the literature and have been used for the synthesis of various new isoxazoline derivatives using
ionic liquid as recyclable solvent. Microwave studies were carried out in Discover Bench Mate system
(Make: CEM-USA) producing continuous irradiation at 2445 MHz and infrared control system. Microwave
experiments were carried out in sealed vessels with an effective magnetic stirring and reflux (which avoids
all problems of non homogeneity in temperature). All other reagents and solvents were purified after
receiving from commercial suppliers. Methyl propiolate, Ethyl propiolate, Propiolic acid, Trimethyl
acetylene, Dimethyl acetylene dicarboxylate etc were obtained commercially from Aldrich, Lancaster,
Fluka and from Sigma-Aldrich, Switzerland and were used without purification, unless otherwise indicated.
Characterization of the novel aziridines have been confirmed on the basis of spectral data. The
microorganisms used in this experiment include 15 bacterial strains of both gram positive & gram negative
varieties. These were obtained from Division of Microbiology, Dept of Pharmaceutical Technology,
Jadavpur University, Kolkata, India.
General procedure for isoxazoline synthesis [15] using ionic liquid (Table 1; entry 1):
2,6-difluoro benzaldehyde (1 mmol) and N-benzylhydroxylamine (1 equivalent) were added to [bmim]BF4
(2 mL) in a 10 ml conical flask, mixed thoroughly and stirred at r.t for 2 h. The formation of nitrone was
monitored by TLC (Rf = 0.40). The nitrone was isolated as white crystalline solid (m.p 420C, uncorrected)
1
following the methodology as adopted in the following cycloaddition reactions. As the nitrone decomposes
on keeping at room temperature, in situ reactions were performed with alkynes. Methyl propiolate (1 mmol)
was added at the time of development of nitrone and the reaction mixture was further stirred at room
temperature for an appropriate time (26 min). After completion of reaction, as indicated by TLC (Rf = 0.58;
ethyl acetate:hexane = 1:10), the reaction mixture was washed with diethyl ether (3x10ml). The combined
ether extracts were concentrated in vacuo and the resulting product was directly charged on silica gel
column and eluted with a mixture of ethyl acetate:n-hexane (1:8) to afford pure isoxazoline 2 (Table 1,
entry 1, 93%). The rest of the viscous ionic liquid was further washed with ether and dried at 80 ◦C under
reduced pressure to retain its activity in subsequent runs.
Spectroscopic data for isoxazoline 2 (Table 1, entry 1): (S)-methyl 2-benzyl-3-(2,6-difluorophenyl)-2,3dihydroisoxazole-5-carboxylate; Yellow gummy mass. Yield 93%; Rf = 0.58; IR (KBr): υmax 3010 (m),
2970 (m), 2246 (m), 1740 (s), 1710 (s), 1690 (s), 1474 (s), 1440 (m), 1324 (m), 1176 (s), 782 (s) cm-1; 1H
NMR (CDCl3): δ 7.87 – 7.80 (m, 3H, C6H3F2), 7.68-7.31 (m, 5H, C6H5), 4.24 (d, J = 7.90 Hz, 1H), 4.12 (d,
J = 7.90 Hz, 1H), 3.38 (s, 3H, -COOCH3), 2.68 (s,2H, C6H5CH2); 13C NMR (CDCl3): δ 173.52 (-C=O),
168.52 (-COOCH3), 137.20, 137.04, 136.87, 136.66 (aromatic carbons), 132.77, 132.35, 132.08, 131.78,
130.80, 129.90 (2,6 difluoro phenyl carbons), 36.80 (benzylic carbon), 31.54, 30.44 (aziridine ring
carbons), 19.26 (-COOCH3); FAB - MS (m/z): 331 (M+), 330, 272, 244 (B.P), 218, 113, 87, 59. Anal.
Calcd. for C18H15O3F2N: C, 65.26; H, 4.56; N, 4.22. Found: C, 65.13; H, 4.41; N, 4.15%.
General procedure for the synthesis of aziridine derivatives under microwave irradiation (entry 1,
Table 1):
Isoxazoline 2 (1.5 mmol, 535 mg) was dissolved in acetonitrile (12 mL) and was heated in a sealed vessel at
110 0C during 5 min under microwave irradiation (400 W, temperature-controlled mode). The resulting
reaction mixture was concentrated under vacuum and the crude material was directly purified by column
chromatography (separation of diastereomers) on silica gel (ethyl acetate/hexane) to give the N-substituted
aziridine 3 (Cis isomer; 359.7 mg, 76%) as a yellow gummy mass. Same methodology was adopted for the
synthesis of other aziridine derivatives 3 (Scheme 1, Table 1).
Spectroscopic data of some new aziridine derivatives
Aziridine 3: methyl 2-((2R,3R)-1-benzyl-3-(2,6-difluorophenyl)aziridin-2-yl)-2-oxoacetate (Table 1, entry
1: Cis isomer): Yellow gummy mass. Yield 76%; Rf = 0.66; IR (KBr): υmax 3010 (m), 2970 (m), 2246 (m),
1740 (s), 1710 (s), 1690 (s), 1474 (s), 1440 (m), 1324 (m), 1176 (s), 782 (s) cm-1; 1H NMR (CDCl3): δ 7.87
– 7.80 (m, 3H, C6H3F2), 7.68-7.31 (m, 5H, C6H5), 4.24 (d, J = 7.90 Hz, 1H), 4.12 (d, J = 7.90 Hz, 1H), 3.38
(s, 3H, -COOCH3), 2.68 (s,2H, C6H5CH2);
C NMR (CDCl3): δ 173.52 (-C=O), 168.52 (-COOCH3),
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137.20, 137.04, 136.87, 136.66 (aromatic carbons), 132.77, 132.35, 132.08, 131.78, 130.80, 129.90 (2,6
difluoro phenyl carbons), 36.80 (benzylic carbon), 31.54, 30.44 (aziridine ring carbons), 18.42 (-COOCH3);
2
FAB - MS (m/z): 331 (M+), 330, 272, 244 (B.P), 218, 113, 87, 59. Anal. Calcd. for C18H15O3F2N: C, 65.26;
H, 4.56; N, 4.22. Found: C, 65.13; H, 4.41; N, 4.15%.
Aziridine 3: methyl 2-((2R,3S)-1-benzyl-3-(2,6-difluorophenyl)aziridin-2-yl)-2-oxoacetate (Table 1, entry
1: Trans isomer): Yellow oil. Yield 12%; Rf = 0.60; IR (KBr): υmax 3014 (m), 2976 (m), 2240 (m), 1744 (s),
1710 (s), 1685 (s), 1470 (s), 1440 (m), 1320 (m), 1172 (s), 780 (s) cm-1; 1H NMR (CDCl3): δ 7.80 – 7.72
(m, 3H, C6H3F2), 7.60-7.43 (m, 5H, C6H5), 4.15 (d, J = 4.20 Hz, 1H), 4.06 (d, J = 4.20 Hz, 1H), 3.30 (s,
3H, -COOCH3), 2.70 (s,2H, C6H5CH2); 13C NMR (CDCl3): δ 174.28 (-C=O), 170.40 (-COOCH3), 135.73,
135.60, 135.46, 135.54 (aromatic carbons), 133.69, 133.26, 132.78, 132.45, 132.23, 131.93 (2,6 difluoro
phenyl carbons), 34.55 (benzylic carbon), 32.27, 31.17 (aziridine ring carbons), 18.24 (-COOCH3); FAB MS (m/z): 331 (M+), 330, 272, 244 (B.P), 218, 217, 113, 87, 59. Anal. Calcd. for C18H15O3F2N: C, 65.26; H,
4.56; N, 4.22. Found: C, 65.07; H, 4.36; N, 4.08%.
Aziridine 3: ethyl 2-((2R,3R)-1-benzyl-3-(2,6-difluorophenyl)aziridin-2-yl)-2-oxoacetate (Table 1, entry 2;
Cis isomer): Colourless gummy mass. Yield 71%; Rf = 0.74; IR (KBr): υmax 3016 (m), 2978 (m), 2350 (m),
1744 (s), 1710 (s), 1685 (s), 1470 (s), 1440 (m), 1330 (m), 1220 (s), 780 (s) cm-1; 1H NMR (CDCl3): δ 7.54
– 7.42 (m, 3H, C6H3F2), 7.22-7.08 (m, 5H, C6H5), 4.52 (d, J = 6.96 Hz, 1H), 4.46 (d, J = 6.96 Hz, 1H), 2.68
(s,2H, C6H5CH2), 2.20 (dd, 2H, J = 4.22 Hz, J = 4.26 Hz, -COOCH2CH3), 1.84 (t, 3H, J = 3.80 Hz, COOCH2CH3);
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C NMR (CDCl3): δ 172.28 (-C=O), 169.80 (-COOCH2CH3), 135.60, 135.44, 135.25,
135.06 (aromatic carbons), 129.46, 129.37, 129.22, 129.07, 128.85, 128.60 (2,6 difluoro phenyl carbons),
35.20 (benzylic carbon), 32.76, 31.90 (aziridine ring carbons), 19.56, 18.74 (-COOCH2CH3); FAB - MS
(m/z): 345 (M+), 300, 272, 244, 232 (B.P), 113, 101, 73, 45. Anal. Calcd. for C19H17O3F2N: C, 66.08; H,
4.95; N, 4.05. Found: C, 66.02; H, 4.83; N, 3.95%.
Aziridine 3: ethyl 2-((2R,3S)-1-benzyl-3-(2,6-difluorophenyl)aziridin-2-yl)-2-oxoacetate (Table 1, entry 2;
Trans isomer): Colourless liquid. Yield 14%; Rf = 0.70; IR (KBr): υmax 3026 (m), 2986 (m), 2280 (m), 1748
(s), 1710 (s), 1680 (s), 1480 (s), 1440 (m), 1336 (m), 1235 (s), 788 (s) cm-1; 1H NMR (CDCl3): δ 7.50 –
7.37 (m, 3H, C6H3F2), 7.16-7.03 (m, 5H, C6H5), 4.46 (d, J = 4.16 Hz, 1H), 4.35 (d, J = 4.16 Hz, 1H), 2.54
(s, 2H, C6H5CH2), 2.34 (dd, 2H, J = 3.90 Hz, J = 3.96 Hz, -COOCH2CH3), 1.70 (t, 3H, J = 3.28 Hz, COOCH2CH3);
13
C NMR (CDCl3): δ 170.80 (-C=O), 168.14 (-COOCH2CH3), 134.46, 134.28, 134.20,
134.12 (aromatic carbons), 130.42, 130.26, 130.12, 130.04, 129.55, 129.47 (2,6 difluoro phenyl carbons),
33.66 (benzylic carbon), 30.40, 29.63 (aziridine ring carbons), 19.52, 18.90 (-COOCH2CH3); FAB - MS
(m/z): 345 (M+), 300, 272, 244, 232 (B.P), 231, 113, 101, 73, 45. Anal. Calcd. for C19H17O3F2N: C, 66.08;
H, 4.95; N, 4.05. Found: C, 65.93; H, 4.78; N, 3.88%.
Aziridine 3: 2-((2R,3R)-1-methyl-3-phenylaziridin-2-yl)-2-oxoacetic acid (Table 1, entry 3; Cis isomer):
Milky gummy mass. Yield 72%; Rf = 0.64; IR (KBr): υmax 3030 (s), 2994 (m), 2446 (m), 1740 (s), 1710 (s),
3
1665 (s), 1460 (s), 1430 (m), 1340 (s), 1230 (s), 776 (s) cm-1; 1H NMR (CDCl3): δ 9.80 (s, 1H, COOH),
6.90 – 6.75 (m, 5H, C6H5), 3.96 (d, J = 7.16 Hz, 1H), 3.80 (d, J = 7.16 Hz, 1H), 1.70 (s, 3H, CH3); 13C
NMR (CDCl3): δ 173.80 (-C=O), 170.27 (-COOH), 134.00, 133.94, 134.80, 134.68 (aromatic carbons),
36.50, 34.63 (aziridine ring carbons), 17.69, (-CH3); FAB - MS (m/z): 205 (M+), 190, 188, 160, 131 (B.P),
117, 73, 45. Anal. Calcd. for C11H11O3N: C, 64.36; H, 5.40; N, 6.82. Found: C, 64.28; H, 5.36; N, 6.70%.
Aziridine 3: 2-((2R,3S)-1-methyl-3-phenylaziridin-2-yl)-2-oxoacetic acid (Table 1, entry 3; Trans isomer):
White liquid. Yield 12%; Rf = 0.60; IR (KBr): υmax 3026 (s), 2990 (m), 2450 (m), 1744 (s), 1714 (s), 1662
(s), 1460 (s), 1435 (m), 1340 (s), 1240 (s), 774 (s) cm-1; 1H NMR (CDCl3): δ 9.86 (s, 1H, COOH), 6.86 –
6.77 (m, 5H, C6H5), 3.80 (d, J = 4.50 Hz, 1H), 3.72 (d, J = 4.50 Hz, 1H), 1.78 (s, 3H, CH3); 13C NMR
(CDCl3): δ 172.34 (-C=O), 170.90 (-COOH), 133.00, 132.90, 132.83, 132.77 (aromatic carbons), 35.60,
34.58 (aziridine ring carbons), 18.82, (-CH3); FAB - MS (m/z): 205 (M+), 190, 188, 160, 131 (B.P), 128,
117, 73, 45. Anal. Calcd. for C11H11O3N: C, 64.36; H, 5.40; N, 6.82. Found: C, 64.25; H, 5.30; N, 6.73%.
Aziridine 3: 2,2-dimethyl-1-((2R,3R)-1-methyl-3-phenylaziridin-2-yl)propan-1-one (Table 1, entry 4; Cis
isomer): Colourless liquid. Yield 70%; Rf = 0.58; IR (KBr): υmax 3165 (s), 3130 (m), 2450 (m), 1720 (s),
1660 (s), 1465 (s), 1430 (m), 1125 (s), 788 (s) cm-1; 1H NMR (CDCl3): δ 6.96 – 6.74 (m, 5H, C6H5), 4.18 (d,
J = 6.90 Hz, 1H), 4.06 (d, J = 6.90 Hz, 1H), 1.80 (s, 3H, CH3), 1.22 (s, 9H); 13C NMR (CDCl3): δ 174.10 (C=O), 130.73, 130.58, 130.46, 130.32 (aromatic carbons), 33.70, 32.66 (aziridine ring carbons), 18.54 (CH3), 15.06 (t-butyl carbon), 12.60, 12.54, 12.50 (methyl carbons attached with t-butyl carbon); FAB - MS
(m/z): 217 (M+), 202, 160, 140, 131 (B.P), 85, 77, 57. Anal. Calcd. for C14H19ON: C, 77.37; H, 8.81; N,
6.45. Found: C, 77.28; H, 8.62; N, 6.26%.
Aziridine 3: 2,2-dimethyl-1-((2R,3S)-1-methyl-3-phenylaziridin-2-yl)propan-1-one (Table 1, entry 4;
Trans isomer): Colourless liquid. Yield 14%; Rf = 0.54; IR (KBr): υmax 3160 (s), 3134 (m), 2445 (m), 1725
(s), 1660 (s), 1460 (s), 1432 (m), 1120 (s), 786 (s) cm-1; 1H NMR (CDCl3): δ 7.06 – 6.92 (m, 5H, C6H5),
4.06 (d, J = 4.24 Hz, 1H), 3.94 (d, J = 4.22 Hz, 1H), 1.72 (s, 3H, CH3), 1.20 (s, 9H); 13C NMR (CDCl3): δ
172.82 (-C=O), 131.60, 131.39, 131.14, 130.95 (aromatic carbons), 32.70, 31.49 (aziridine ring carbons),
18.14 (-CH3), 16.20 (t-butyl carbon), 13.68, 13.50, 13.33 (methyl carbons attached with t-butyl carbon);
FAB - MS (m/z): 217 (M+), 202, 160, 139, 132, 131 (B.P), 85, 77, 57. Anal. Calcd. for C14H19ON: C, 77.37;
H, 8.81; N, 6.45. Found: C, 77.20; H, 8.66; N, 6.30%.
Aziridine 3 ((2R,3R)-1-methyl-3-phenylaziridin-2-yl)(trimethylsilyl)methanone (Table 1, entry 5; Cis
isomer): Pale yellow liquid. Yield 71%; Rf = 0.68; IR (KBr): υmax 3140 (s), 3010 (m), 2840 (m), 1710 (s),
1650 (s), 1445 (s), 1400 (m), 1240 (s), 778 (s) cm-1; 1H NMR (CDCl3): δ 6.62 – 6.50 (m, 5H, C6H5), 4.80 (d,
J = 7.26 Hz, 1H), 4.64 (d, J = 7.26 Hz, 1H), 1.69 (s, 3H, CH3), 0.10 (s, 9H); 13C NMR (CDCl3): δ 170.56 (C=O), 129.48, 129.32, 129.20, 129.05 (aromatic carbons), 31.60, 30.32 (aziridine ring carbons), 19.42 (-
4
CH3), 0.10 (trimethyl silyl carbons); FAB - MS (m/z): 233 (M+), 218, 160, 155, 132, 117 (B.P), 77, 55.
Anal. Calcd. for C13H19SiON: C, 66.91; H, 8.20; N, 6.00. Found: C, 66.64; H, 8.16; N, 5.83%.
Aziridine 3 ((2R,3S)-1-methyl-3-phenylaziridin-2-yl)(trimethylsilyl)methanone (Table 1, entry 5; Trans
isomer): Yellow liquid. Yield 11%; Rf = 0.62; IR (KBr): υmax 3152 (s), 3014 (m), 2846 (m), 1710 (s), 1655
(s), 1436 (s), 1410 (m), 1236 (s), 776 (s) cm-1; 1H NMR (CDCl3): δ 6.69 – 6.50 (m, 5H, C6H5), 4.73 (d, J =
3.90 Hz, 1H), 4.60 (d, J = 3.90 Hz, 1H), 1.64 (s, 3H, CH3), 0.10 (s, 9H); 13C NMR (CDCl3): δ 171.96 (C=O), 127.80, 127.75, 127.66, 127.54 (aromatic carbons), 33.58, 31.80 (aziridine ring carbons), 17.63 (CH3), 0.10 (trimethyl silyl carbons); FAB - MS (m/z): 233 (M+), 218, 160, 155, 132, 117 (B.P), 77. Anal.
Calcd. for C13H19SiON: C, 66.91; H, 8.20; N, 6.00. Found: C, 66.61; H, 8.13; N, 5.88%.
Aziridine 3: methyl 2-((2R,3R)-3-(2,6-difluorophenyl)-1-methylaziridin-2-yl)-2-oxoacetate (Table 1, entry
6: Cis isomer): Colourless liquid. Yield 69%; Rf = 0.60; IR (KBr): υmax 3020 (m), 2960 (m), 2240 (m), 1740
(s), 1710 (s), 1680 (s), 1475 (s), 1460 (m), 1320 (m), 1170 (s), 786 (s) cm-1; 1H NMR (CDCl3): δ 7.30 –
7.16 (m, 3H, C6H3F2), 4.54 (d, J = 6.86 Hz, 1H), 4.47 (d, J = 6.86 Hz, 1H), 3.34 (s, 3H, -COOCH3), 1.96
(s,3H, N-CH3); 13C NMR (CDCl3): δ 175.13 (-C=O), 170.22 (-COOCH3), 128.80, 128.65, 128.52, 128.27
(aromatic carbons), 33.70, 32.62 (aziridine ring carbons), 17.80 (-COOCH3), 15.84 (N-CH3); FAB - MS
(m/z): 255 (M+), 240, 196, 168, 167 (B.P), 142, 113, 87, 59. Anal. Calcd. for C12H11O3F2N: C, 56.47; H,
4.34; N, 5.48. Found: C, 56.34; H, 4.30; N, 5.29%.
Aziridine 3: methyl 2-((2R,3S)-3-(2,6-difluorophenyl)-1-methylaziridin-2-yl)-2-oxoacetate (Table 1, entry
6: Trans isomer): Colourless liquid. Yield 13%; Rf = 0.56; IR (KBr): υmax 3016 (m), 2955 (m), 2740 (m),
2440 (m), 1735 (s), 1712 (s), 1685 (s), 1475 (s), 1446 (m), 1330 (m), 1205 (s), 780 (s) cm -1; 1H NMR
(CDCl3): δ 7.06 – 6.87 (m, 3H, C6H3F2), 4.13 (d, J = 4.15 Hz, 1H), 4.06 (d, J = 4.16 Hz, 1H), 3.30 (s, 3H, COOCH3), 2.05 (s,3H, N-CH3); 13C NMR (CDCl3): δ 174.76 (-C=O), 171.57 (-COOCH3), 127.93, 127.80,
127.68, 127.51 (aromatic carbons), 35.06, 33.47 (aziridine ring carbons), 19.73 (-COOCH3), 17.42 (NCH3); FAB - MS (m/z): 255 (M+), 240, 196, 168, 167 (B.P), 142, 141, 113, 87, 59. Anal. Calcd. for
C12H11O3F2N: C, 56.47; H, 4.34; N, 5.48. Found: C, 56.30; H, 4.22; N, 5.31%.
11. Spectroscopic data for aziridine 3 (Table 1, entry 6: Cis isomer): Colourless liquid. Yield 69%; Rf =
0.60; IR (KBr): υmax 3020 (m), 2960 (m), 2240 (m), 1740 (s), 1710 (s), 1680 (s), 1475 (s), 1460 (m), 1320
(m), 1170 (s), 786 (s) cm-1; 1H NMR (CDCl3): δ 7.30 – 7.16 (m, 3H, C6H3F2), 4.54 (d, J = 6.86 Hz, 1H),
4.47 (d, J = 6.86 Hz, 1H), 3.34 (s, 3H, -COOCH3), 1.96 (s,3H, N-CH3); 13C NMR (CDCl3): δ 175.13 (C=O), 170.22 (-COOCH3), 128.80, 128.65, 128.52, 128.27 (aromatic carbons), 33.70, 32.62 (aziridine ring
carbons), 17.80 (-COOCH3), 15.84 (N-CH3); FAB - MS (m/z): 255 (M+), 240, 196, 168, 167 (B.P), 142,
113, 87, 59. Anal. Calcd. for C12H11O3F2N: C, 56.47; H, 4.34; N, 5.48. Found: C, 56.34; H, 4.30; N, 5.29%.
12. Spectroscopic data for aziridine 3 (Table 1, entry 6: Trans isomer): Colourless liquid. Yield 13%; Rf =
0.56; IR (KBr): υmax 3016 (m), 2955 (m), 2740 (m), 2440 (m), 1735 (s), 1712 (s), 1685 (s), 1475 (s), 1446
5
(m), 1330 (m), 1205 (s), 780 (s) cm-1; 1H NMR (CDCl3): δ 7.06 – 6.87 (m, 3H, C6H3F2), 4.13 (d, J = 4.15
Hz, 1H), 4.06 (d, J = 4.16 Hz, 1H), 3.30 (s, 3H, -COOCH3), 2.05 (s,3H, N-CH3);
13
C NMR (CDCl3): δ
174.76 (-C=O), 171.57 (-COOCH3), 127.93, 127.80, 127.68, 127.51 (aromatic carbons), 35.06, 33.47
(aziridine ring carbons), 19.73 (-COOCH3), 17.42 (N-CH3); FAB - MS (m/z): 255 (M+), 240, 196, 168, 167
(B.P), 142, 141, 113, 87, 59. Anal. Calcd. for C12H11O3F2N: C, 56.47; H, 4.34; N, 5.48. Found: C, 56.30; H,
4.22; N, 5.31%.
13. Spectroscopic data for aziridine 3 (Table 1, entry 7: Cis isomer): Gray sticky liquid. Yield 72%; Rf =
0.70; IR (KBr): υmax 3190 (m), 2995 (m), 2310 (m), 1730 (s), 1710 (s), 1685 (s), 1470 (s), 1465 (m), 1320
(m), 1180 (s), 784 (s) cm-1; 1H NMR (CDCl3): δ 7.12 – 7.00 (m, 5H, C6H5), 6.80 – 6.73 (m, 3H, aromatic
protons), 4.27 (d, J = 7.40 Hz, 1H), 4.10 (d, J = 7.40 Hz, 1H), 3.30 (s, 3H, -COOCH3), 2.07 (s, 2H,
CH2C6H5);
C NMR (CDCl3): δ 174.72 (-C=O), 172.53 (-COOCH3), 136.84, 136.42, 136.21, 135.10
13
(aromatic carbons), 131.75, 131.40, 131.26, 131.04 (furan ring carbons), 30.80, 28.47 (aziridine ring
carbons), 23.15 (CH2C6H5), 18.53 (-COOCH3); FAB - MS (m/z): 285 (M+), 226, 218, 197 (B.P), 127, 91,
89, 59. Anal. Calcd. for C16H15O4N: C, 67.35; H, 5.29; N, 4.91. Found: C, 67.29; H, 5.23; N, 4.80%.
15. Spectroscopic data for aziridine 3 (Table 1, entry 7: Trans isomer): Dark gray sticky liquid. Yield 10%;
Rf = 0.64; IR (KBr): υmax 3185 (m), 2990 (m), 2320 (m), 1735 (s), 1712 (s), 1682 (s), 1475 (s), 1462 (m),
1330 (m), 1185 (s), 780 (s) cm-1; 1H NMR (CDCl3): δ 7.16 – 7.05 (m, 5H, C6H5), 6.88 – 6.77 (m, 3H,
aromatic protons), 4.22 (d, J = 3.86 Hz, 1H), 4.04 (d, J = 3.84 Hz, 1H), 3.34 (s, 3H, -COOCH3), 2.00 (s,
2H, CH2C6H5); 13C NMR (CDCl3): δ 173.80 (-C=O), 172.47 (-COOCH3), 132.75, 132.57, 132.52, 132.18
(aromatic carbons), 130.22, 130.16, 130.05, 129.87 (furan ring carbons), 32.90, 30.61 (aziridine ring
carbons), 22.70 (CH2C6H5), 17.88 (-COOCH3); FAB - MS (m/z): 285 (M+), 226, 218, 197 (B.P), 194, 127,
91, 89, 67, 59. Anal. Calcd. for C16H15O4N: C, 67.35; H, 5.29; N, 4.91. Found: C, 67.22; H, 5.16; N, 4.66%.
16. Spectroscopic data for aziridine 3 (Table 1, entry 8; Cis isomer): Pale yellow gummy mass. Yield 70%;
Rf = 0.70; IR (KBr): υmax 3134 (m), 3090 (m), 2260 (m), 1745 (s), 1708 (s), 1680 (s), 1470 (s), 1434 (m),
1320 (m), 1245 (s), 774 (s) cm-1; 1H NMR (CDCl3): δ 7.88 – 7.76 (m, 3H, aromatic protons), 7.54-7.31 (m,
5H, C6H5), 4.17 (d, J = 6.82 Hz, 1H), 4.06 (d, J = 6.82 Hz, 1H), 2.78 (s,2H, C6H5CH2), 2.20 (dd, 2H, J =
3.80 Hz, J = 3.74 Hz, -COOCH2CH3), 1.80 (t, 3H, J = 1.94 Hz, -COOCH2CH3);
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C NMR (CDCl3): δ
170.84 (-C=O), 168.44 (-COOCH2CH3), 134.77, 134.52, 134.43, 134.35 (furan ring carbons), 128.84,
128.70, 128.62, 128.49 (aromatic carbons), 32.64 (benzylic carbon), 34.80, 32.57 (aziridine ring carbons),
17.47, 16.53 (-COOCH2CH3); FAB - MS (m/z): 299 (M+), 232, 226, 222, 197 (B.P), 141, 101, 91. Anal.
Calcd. for C17H17O4N: C, 68.21; H, 5.72; N, 4.68. Found: C, 68.12; H, 5.63; N, 4.50%.
17. Spectroscopic data for aziridine 3 (Table 1, entry 8; Trans isomer): Colourless liquid. Yield 11%; Rf =
0.63; IR (KBr): υmax 3126 (m), 3084 (m), 2265 (m), 1748 (s), 1700 (s), 1680 (s), 1472 (s), 1430 (m), 1330
(m), 1240 (s), 783 (s) cm-1; 1H NMR (CDCl3): δ 7.36 – 7.26 (m, 3H, aromatic protons), 7.11-7.04 (m, 5H,
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C6H5), 4.34 (d, J = 3.66 Hz, 1H), 4.28 (d, J = 3.60 Hz, 1H), 2.74 (s,2H, C6H5CH2), 2.69 (dd, 2H, J = 3.20
Hz, J = 3.20 Hz, -COOCH2CH3), 1.70 (t, 3H, J = 1.48 Hz, -COOCH2CH3); 13C NMR (CDCl3): δ 170.60 (C=O), 167.68 (-COOCH2CH3), 133.50, 133.38, 133.22, 133.12 (furan ring carbons), 128.50, 128.36,
127.87, 127.70 (aromatic carbons), 33.47 (benzylic carbon), 30.83, 30.27 (aziridine ring carbons), 19.05,
18.51 (-COOCH2CH3); FAB - MS (m/z): 299 (M+), 232, 226, 222, 198, 197 (B.P), 141, 101, 91, 67. Anal.
Calcd. for C17H17O4N: C, 68.21; H, 5.72; N, 4.68. Found: C, 68.10; H, 5.56; N, 4.40%.
18. Spectroscopic data for aziridine 3 (Table 1, entry 9; Cis isomer): Colourless liquid. Yield 64%; Rf =
0.62; IR (KBr): υmax 3155 (s), 3134 (s), 2465 (m), 1715 (s), 1660 (s), 1480 (s), 1445 (m), 1200 (s), 772 (s)
cm-1; 1H NMR (CDCl3): δ 6.92 – 6.85 (m, 3H, aromatic protons), 6.60 – 6.44 (m, 5H, C6H5), 4.55 (d, J =
7.48 Hz, 1H), 4.36 (d, J = 7.50 Hz, 1H), 2.14 (s, 2H, CH2C6H5), 1.30 (s, 9H); 13C NMR (CDCl3): δ 173.64
(-C=O), 135.21, 135.10, 134.85, 134.73 (phenyl ring aromatic carbons), 130.60, 130.54, 130.37, 130.23
(furan ring aromatic carbons), 34.50, 33.42 (aziridine ring carbons), 27.30 (-CH2C6H5), 16.07 (t-butyl
carbon), 14.55, 14.32, 14.16 (methyl carbons attached with t-butyl carbon); FAB - MS (m/z): 283 (M+), 226,
215 (B.P), 198, 125, 91, 77, 57. Anal. Calcd. for C18H21O2N: C, 76.29; H, 7.46; N, 4.94. Found: C, 76.20;
H, 7.34; N, 4.80%.
19. Spectroscopic data for aziridine 3 (Table 1, entry 9; Trans isomer): Colourless liquid. Yield 16%; Rf =
0.56; IR (KBr): υmax 3148 (s), 3130 (s), 2460 (m), 1720 (s), 1655 (s), 1484 (s), 1448 (m), 1190 (s), 775 (s)
cm-1; 1H NMR (CDCl3): δ 6.83 – 6.72 (m, 3H, aromatic protons), 6.46 – 6.30 (m, 5H, C6H5), 4.28 (d, J =
4.00 Hz, 1H), 4.16 (d, J = 4.00 Hz, 1H), 2.42 (s, 2H, CH2C6H5), 1.24 (s, 9H); 13C NMR (CDCl3): δ 172.00
(-C=O), 133.70, 133.42, 133.26, 133.18 (phenyl ring aromatic carbons), 131.66, 131.40, 131.36, 131.17
(furan ring aromatic carbons), 36.80, 34.52 (aziridine ring carbons), 24.31 (-CH2C6H5), 19.26 (t-butyl
carbon), 15.28, 14.78, 14.60 (methyl carbons attached with t-butyl carbon); FAB - MS (m/z): 283 (M+), 226,
216, 215 (B.P), 198, 125, 91, 77, 57. Anal. Calcd. for C18H21O2N: C, 76.29; H, 7.46; N, 4.94. Found: C,
76.15; H, 7.26; N, 4.84%.
References
1 (a) Tufariello, J. J. 1,3-Dipolar Cycloaddition Chemistry; Padwa, A., Ed.; Wiley-Interscience: New York,
NY, 1984; Vol. 2, Chapter 9, pp 83–168; (b) Confalone, P. N.; Huie, E. M. Org.
React. 1988, 36, 1–173 (c) Baldwin, S. W.; McFayden, R. B.; Aube, J.; Wilson, J. D. Tetrahedron Lett.
1991, 32, 4431–4434.
2. For reviews on reaction of aziridines, see: (a) Tanner, D. Angew. Chem., Int.Ed.Engl. 1994, 33, 599–619.
(b) Aziridines and Epoxides in Organic Synthesis; Yudin, A. K., Ed.;Wiley-VCH Verlag GmbH & Co.
KGaA, Weinheim, 2006 (c) Padwa, A. in Comprehensive Heterocyclic Chemistry, Vol III, Katritzky, A.R.,
Ed., Elsevier 2008, Vol 18, pp 1-97. (d) Sweeney, J. B. In Science of synthesis; Shaumann, E., Enders, D.,
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Eds; Thieme, Stuttgart, 2009; Vol 40a, Chapter 40.1.5. (e) Schneider, C. Angew. Chem., Int. Ed. Engl.
2009, 48, 2082–2084 (f) Dauban, P.; Malik, G. Angew. Chem., Int. Ed. Engl. 2009, 48, 9026–9029 (g) Lu,
P. Tetrahedron, 2010, 66, 2549–2560.
3. Deshong, P.; Li, W.; Kennington, J.W.; Ammon, H.L.
J.Org.Chem. 1991, 56, 1364-1369.
4. (i) Etiemey, J. P.; Lidstrom, P. Microwave assisted organic synthesis (Blackwell Publishing), 2005 (ii)
Loupy, A. Microwaves in organic synthesis (Wiley-VCH;Weinheim), 2002 (iii) Alvareg, H. M.; Loupy, A.;
Caldron, O.; Periz, E. Tetrahedron, 2006, 62, 2616-2621.
Note : All the Spectra of the aziridine derivatives are available with author.
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