S. Yang et al. / Tetrahedron 63 (2007) 5470–5476
5473
(d, Jc-p¼8.5 Hz), 29.3 (d, Jc-p¼4.3 Hz, 6). Anal. Calcd for
C17H25ClN3O9P: C, 42.38; H, 5.23; N, 8.72; P, 6.43. Found:
C, 42.67; H, 5.22; N, 9.02; P, 6.36%.
4.3.4. 2-[(2-Chloroethyl)(2-hydroxyethyl)amino]-3,5-di-
nitro-N-[2-(tetrahydro-2H-pyran-2-yloxy)ethyl]benz-
amide (12a). From 2-chloro-3,5-dinitro-N-[2-(tetrahydro-
2H-pyran-2-yloxy)ethyl]benzamide6 (11) as a yellow solid
1
4.2.2. tert-Butyl 3-chloro-2,6-dinitrobenzoate (26). A mix-
ture of 3-chloro-2,6-dinitrobenzoic acid11 (3.00 g, 12 mmol),
tert-butyl acetate (20 mL, 150 mmol) and 70% HClO4
(0.8 mL) was stirred at 35 ꢁC for 6 h, then poured into excess
satd aqueous NaHCO3. The mixture was extracted with
CH2Cl2 and the organic phase was washed with satd aqueous
NaHCO3 andwater,driedandevaporatedtodryness.Theresi-
due was crystallised from hexane to give 26 (2.51 g, 68%) as
a white solid: mp 109–110 ꢁC; 1H NMR [(CD3)2SO] d 8.43
(d, J¼8.9 Hz, 1H), 8.22 (d, J¼8.9 Hz, 1H), 1.49 (s, 9H).
Anal. Calcd for C11H11ClN2O6: C, 43.65; H, 3.66; N, 9.26.
Found: C, 43.93; H, 3.68; N, 9.30%.
(97% yield): mp (EtOAc/petroleum ether) 106–108 ꢁC; H
NMR [(CD3)2SO] d 9.07 (t, J¼5.4 Hz, 1H), 8.70 (d,
J¼2.8 Hz, 1H), 8.33 (d, J¼2.8 Hz, 1H), 5.15 (t, J¼5.6 Hz,
1H), 4.62 (t, J¼3.7 Hz, 1H), 3.78 (m, 4H), 3.58–3.43 (m,
8H), 3.14 (m, 2H), 1.80–1.40 (m, 6H); 13C NMR d 165.7,
146.8, 143.7, 139.7, 133.9, 128.4, 123.1, 98.0, 64.8, 61.5,
57.8, 54.3, 53.3, 41.4, 39.5, 30.1, 24.9, 19.1. Anal. Calcd
for C18H25ClN4O8: C, 46.91; H, 5.47; N, 12.16. Found: C,
47.08; H, 5.43; N, 12.21%.
4.3.5. 2-[(2-Bromoethyl)(2-hydroxyethyl)amino]-3,5-di-
nitro-N-[2-(tetrahydro-2H-pyran-2-yloxy)ethyl]benz-
amide (12b). From 11 as a yellow solid (80% yield): mp
(EtOAc/heptane) 121–123 ꢁC; 1H NMR [(CD3)2SO] d 9.06
(t, J¼5.4 Hz, 1H), 8.70 (d, J¼2.8 Hz, 1H), 8.33 (d,
J¼2.8 Hz, 1H), 5.15 (t, J¼5.5 Hz, 1H), 4.62 (t, J¼3.5 Hz,
1H), 3.78 (m, 2H), 3.63–3.43 (m, 10H), 3.15 (m, 2H), 1.80–
1.40 (m, 6H); 13C NMR d 165.7, 146.6, 143.8, 139.8, 134.0,
128.4, 123.0, 98.0, 64.8, 61.5, 57.9, 54.1, 53.4, 39.5, 30.1,
29.8, 24.9, 19.1. Anal. Calcd for C18H25BrN4O8: C, 42.79;
H, 4.99; N, 11.09. Found: C, 42.82; H, 4.96; N, 11.03%.
4.3. Aziridineethanol reaction: general conditions
A slurry of aromatic chloride (1 equiv) and either LiCl
(0.5 equiv), LiBr (17 equiv) or NaI (17 equiv) in solvent (3-
methyl-2-butanone unless otherwise mentioned for specific
products) was cooled to below 5 ꢁC. Aziridineethanol
(2.5 equiv) was added over 10 min to the stirred mixture,
which was kept below 20 ꢁC overnight. Water was added,
and the reaction mixture was extracted three times with
EtOAc. The combined organic layers were washed with
water and with a 10% aqueous solution of the appropriate so-
dium halide, dried and concentrated under reduced pressure.
The concentrate was passed through a short column of silica
gel, eluting with EtOAc/heptane, to provide product. The fol-
lowing compounds were prepared by this method.
4.3.6. 2-[(2-Hydroxyethyl)(2-iodoethyl)amino]-3,5-dini-
tro-N-[2-(tetrahydro-2H-pyran-2-yloxy)ethyl]benz-
amide (12c). From 11 as a yellow foam (63% yield); H
1
NMR (CDCl3) d 8.63 (d, J¼2.8 Hz, 1H), 8.56 (d, J¼
2.8 Hz, 1H), 8.24 (br, 1H), 4.54 (m, 1H), 4.48 (m, 1H),
3.93 (m, 2H), 3.84 (m, 1H), 3.70 (m, 6H), 3.54 (m, 1H),
3.30 (m, 2H), 3.18 (m, 2H), 1.90–1.40 (m, 6H); 13C NMR
d 165.7, 146.7, 144.4, 140.9, 134.5, 129.2, 123.5, 101.6,
67.0, 65.4, 58.0, 55.0, 53.7, 40.7, 31.3, 25.1, 21.2, 0.3;
HRMS (FAB) calcd for C18H26IN4O8 [M+H]+ m/z
553.0795; found 533.0797.
4.3.1. 2-[(2-Chloroethyl)(2-hydroxyethyl)amino]-3,5-di-
nitrobenzamide (9a). From 2-chloro-3,5-dinitrobenz-
amide6 (8) (in THF) as a yellow solid (92% yield): mp
(EtOAc/petroleum ether) 96–100 ꢁC; 1H NMR [(CD3)2SO]
d 8.69 (d, J¼2.8 Hz, 1H), 8.43 (s, 1H), 8.35 (d, J¼2.8 Hz,
1H), 8.10 (s, 1H), 5.15 (t, J¼5.6 Hz, 1H), 3.77 (m, 2H),
3.54 (m, 4H), 3.14 (m, 2H); 13C NMR d 167.6, 146.7,
143.8, 139.7, 134.1, 128.2, 123.1, 57.8, 54.3, 53.6, 41.4.
Anal. Calcd for C11H13ClN4O6$0.5H2O: C, 38.66; H, 4.13;
N, 16.40. Found: C, 38.37; H, 4.42; N, 15.68%.
4.3.7. tert-Butyl 2-[(2-hydroxyethyl)(2-chloroethyl)-
amino]-3,5-dinitrobenzoate (18). From tert-butyl 2-chloro-
3,5-dinitrobenzoate9 (17) (in DMF) as a yellow solid (63%
yield): mp (EtOAc/petroleum ether) 106–107 ꢁC; 1H NMR
[(CD3)2SO] d 8.73 (d, J¼2.8 Hz, 1H), 8.44 (d, J¼2.8 Hz,
1H), 4.58 (t, J¼5.4 Hz, 1H), 3.75 (t, J¼6.7 Hz, 2H), 3.55
(q, J¼5.7 Hz, 2H), 3.46 (t, J¼6.7 Hz, 2H), 3.19 (t, J¼
5.9 Hz, 2H), 1.60 (s, 9H). Anal. Calcd for C15H20ClN3O7:
C, 46.22; H, 5.17; N, 10.78; Cl, 9.10. Found: C, 46.50;
H, 5.23; N, 10.66; Cl, 9.05%.
4.3.2. 2-[(2-Bromoethyl)(2-hydroxyethyl)amino]-3,5-di-
nitrobenzamide (9b). From 8 as a yellow solid (87% yield):
mp (EtOAc/petroleum ether) 138–140 ꢁC; 1H NMR
[(CD3)2SO] d 8.69 (d, J¼2.8 Hz, 1H), 8.43 (s, 1H), 8.35
(d, J¼2.8 Hz, 1H), 8.10 (s, 1H), 5.15 (t, J¼5.6 Hz, 1H),
3.61 (m, 4H), 3.53 (m, 2H), 3.14 (m, 2H); 13C NMR
d 167.6, 146.4, 143.8, 139.8, 134.2, 128.2, 123.0, 57.8,
54.1, 53.6, 29.8. Anal. Calcd for C11H13BrN4O6: C, 35.0;
H, 3.5; N, 14.9. Found: C, 35.0; H, 3.5; N, 14.6%.
4.3.8. 5-[(2-Chloroethyl)(2-hydroxyethyl)amino]-2,4-di-
nitrobenzamide (21a). From 5-chloro-2,4-dinitrobenz-
amide11 (20) (in DMF) as a yellow solid (43% yield): mp
(EtOAc/petroleum ether) 131–134 ꢁC; 1H NMR [(CD3)2SO]
d 8.48 (s, 1H), 8.10 (s, 1H), 7.75 (s, 1H), 7.35 (s, 1H), 4.76
(vbr s, 1H), 3.83 (t, J¼5.9 Hz, 2H), 3.75 (t, J¼5.9 Hz, 2H),
3.56 (t, J¼5.4 Hz, 2H), 3.36 (t, J¼5.5 Hz, 2H); 13C NMR
d 166.3, 147.3, 137.4, 136.9, 135.0, 124.3, 119.8, 58.1, 54.1,
52.5, 41.3. Anal. Calcd for C11H13ClN4O6: C, 39.71; H,
3.94; N, 16.84. Found: C, 39.79; H, 3.95; N, 16.61%.
4.3.3. 2-[(2-Hydroxyethyl)(2-iodoethyl)amino]-3,5-dini-
trobenzamide (9c). From 8 as a yellow solid (70% yield):
mp (EtOAc/petroleum ether) 152–155 ꢁC; 1H NMR
[(CD3)2SO] d 8.69 (d, J¼2.8 Hz, 1H), 8.41 (s, 1H), 8.34
(d, J¼2.8 Hz, 1H), 8.10 (s, 1H), 5.13 (t, J¼5.6 Hz, 1H),
3.53 (m, 4H), 3.35 (m, 2H), 3.13 (m, 2H); 13C NMR
d 167.5, 146.1, 143.8, 139.8, 134.2, 128.2, 123.0, 57.8,
54.8, 53.7, 2.07. Anal. Calcd for C11H13IN4O6: C, 31.15;
H, 3.09; N, 13.21. Found: C, 31.45; H, 2.99; N, 12.91%.
4.3.9. Methyl 3-[(2-chloroethyl)(2-hydroxyethyl)amino]-
2,6-dinitrobenzoate (24a). From methyl 3-chloro-2,6-di-
nitrobenzoate12 (23) (in DMF) as a yellow oil (63% yield);