Med Chem Res
was chromatographed on silica gel using ethyl acetate to
1,671 (NHC=O), 1,524 (NO2 assym stretch), 1,484 (C=C),
1,227, 1,123 (C–N), 759 (C–Cl); 1H-NMR (CDCl3) d
(ppm): 3.75(t, 4H, J = 7.84 Hz, –N(CH2CH2Cl)2) 4.12 (s,
2H, –COCH2N), 4.57 (t, 4H, J = 7.82 Hz, –N(CH2
CH2Cl)2), 7.50–7.68 (m, 8H, ArH), 11.26 (br s, 1H,
furnish compounds (5a–f).
2-{N,N-bis(20-chloroethyl)}aminoacetamido-5-
chlorobenzophenone (5a)
exchangeable, –NHCOCH2–); 13C-NMR (CDCl3)
d
Yield = 65 %, brown oil. Rf: 0.68 (chloroform: methanol:
9.5:0.5); IR KBr (cm21): 3,336 (N–H), 3,094, 2,943 (C–H),
1,699 (C=O), 1,685 (NHC=O), 1,486 (C=C), 1,214, 1,120,
1,097 (C–N), 754 (C–Cl); 1H-NMR (CDCl3) d (ppm): 3.05 (t,
4H, J = 8.0 Hz, –N(CH2CH2Cl)2), 3.42 (s, 2H, –COCH2N),
3.63 (t, 4H, J = 7.5 Hz, –N(CH2CH2Cl)2), 7.17–7.55(m, 8H,
ArH), 9.67 (br s, 1H, exchangeable, –NHCOCH2–); 13C-
NMR (CDCl3) d (ppm): 42.8 (2xC-Cl), 56.4 (2xC-N), 58.0
(CH2), 123.4, 125.7, 126.0, 128.4, 129.4, 130.4, 131.2, 132.8,
140.6, 142.8 (Aromatic), 174.0 (–NHC=O), 190.0 (C=O);
TOF MS ES1m/z: 437(M ? H ? Na)?.
(ppm): 43.2 (2xC-Cl), 56.4 (2xC-N), 58.2 (CH2), 122.4,
125.7, 126.8, 128.4, 130.5, 131.2, 132.8, 140.6, 142.8,
147.8 (Aromatic), 168.4 (–NHC=O), 195.0 (C=O); TOF
MS ES1 m/z: 447 (M ? Na)?.
2-{N,N-bis(20-chloroethyl)}aminoacetamido-20-chloro-
5-nitrobenzophenone (5e)
Yield = 52 %, red oil. Rf: 0.52 (ethyl acetate). IR KBr
(cm21): 3,350 (N–H), 3,080, 2,967 (C–H), 1,691 (C=O),
1,672 (NHC=O), 1,526 (NO2 assym stretch), 1,489 (C=C),
1,222, 1,124 (C–N), 758 (C–Cl); 1H-NMR (CDCl3) d
(ppm): 3.75 (t, 4H, J = 8.0 Hz, –N(CH2CH2Cl)2),
4.11 (s, 2H, –COCH2N), 4.55 (t, 4H, J = 8.1 Hz,
–N(CH2CH2Cl)2), 7.20–7.70 (m, 7H, ArH), 11.26 (br s,
1H, exchangeable, –NHCOCH2–); 13C-NMR (CDCl3) d
(ppm): 42.3 (2xC-Cl), 56.4 (2xC-N), 58.3 (CH2), 123.8,
125.7, 126.8, 127.2, 127.9, 128.4, 129.4, 130.4, 131.2,
134.8, 136.0, 152 (Aromatic), 168.0 (–NHC=O), 197.0
(C=O); TOF MS ES1 m/z: 481 (M ? Na)?.
2-{N,N-bis(20-chloroethyl)}aminoacetamido-5,20-
dichlorobenzophenone (5b)
Yield = 68 %, brown oil. Rf: 0.82 (chloroform: methanol:
9.8:0.2). IR KBr (cm21): 3,342 (N–H), 3,088, 2,940 (C–H),
1,694 (C=O), 1,680 (NHC=O), 1,476 (C=C), 1,219, 1,120,
1,086(C–N),756(C–Cl);1H-NMR (CDCl3) d(ppm):3.20(t,
4H, J = 7.6 Hz, –N(CH2CH2Cl)2), 3.70 (s, 2H, –COCH2N),
3.90 (t, 4H, J = 7.8 Hz, –N(CH2CH2Cl)2), 7.20–7.70(m, 7H,
ArH), 12.0 (br s, 1H, exchangeable, –NHCOCH2–); 13C–
NMR (CDCl3) d (ppm): 42.5(2xC-Cl), 56.8 (2xC-N), 58.5
(CH2), 123.2, 125.7, 126.8, 126.4, 127.9, 128.4, 129.4, 130.4,
131.2, 134.8, 140.8, 142.8 (Aromatic), 171.0 (–NHC=O),
197.0 (C=O); TOF MS ES1m/z: 472(M ? H ? Na)?.
2-{N,N-bis(20-chloroethyl)}aminoacetamido-40-chloro-
5-nitrobenzophenone (5f)
Yield = 56 %, red oil. Rf: 0.65 (ethyl acetate). IR KBr
(cm21): 3,354 (N–H), 3,016 (C–H), 1,685 (C=O), 1,677
(NHC=O), 1,521 (NO2 assym stretch), 1,485 (C=C), 1,219,
1,124 (C–N), 754 (C–Cl); 1H-NMR (CDCl3) d (ppm):
3.75(t, 4H, J = 7.84 Hz, –N(CH2CH2Cl)2), 4.12 (s, 2H,
–COCH2N), 4.57 (t, 4H, J = 7.82 Hz, –N(CH2CH2Cl)2),
7.50–7.70 (m, 7H, ArH), 11.38 (br s, 1H, exchangeable,
-NHCOCH2-); 13C-NMR (CDCl3) d (ppm): 42.4 (2xC-Cl),
55.6 (2xC-N), 57.5 (CH2), 122.8, 125.0, 125.8, 128.6,
130.2, 131.2, 137.0, 138.0, 144, 148 (Aromatic), 167.0
(–NHC=O), 195.0 (C=O); TOF MS ES1 m/z: 481
(M ? Na)?.
2-{N,N-bis(20-chloroethyl)}aminoacetamido-5,40-
dichlorobenzophenone (5c)
Yield = 64 %, brown oil. Rf: 0.91 (chloroform:methanol:
9.8:0.2). IR KBr (cm21): 3,345 (N–H), 3,087, 2,950 (C–H),
1,696 (C=O), 1,683 (NHC=O), 1,470 (C=C), 1,216, 1,122,
1,090 (C–N), 754 (C–Cl); 1H-NMR (CDCl3) d (ppm):
3.02(t, 4H, J = 8.2 Hz, –N(CH2CH2Cl)2), 3.45 (s, 2H,
–COCH2N), 3.64 (t, 4H, J = 8.0 Hz, –N(CH2CH2Cl)2),
7.20–8.58 (m, 7H, ArH), 11.27 (br s, 1H, exchangeable,
–NHCOCH2–); 13C-NMR (CDCl3) d (ppm): 42.5 (2xC-Cl),
56.8 (2xC-N), 58.5 (CH2), 123.2, 126.8, 128.4, 129.4, 130.4,
130.8, 131.2, 137.0, 138.0, 142.8 (Aromatic), 167.0
(–NHC=O), 194.0 (C=O); TOF MS ES1m/z: 448(M)?.
NBP alkylation assay
All compounds were checked for their NBP alkylating
activity by procedure mentioned before (Balazs et al.,
1970). Chlorambucil (1.0 mg) was dissolved in 20.0 ml of
95 % EtOH. A 1.0 ml aliquot of this solution was placed in
a 5.0 ml volumetric flask together with 1.0 ml of NBP
solution (3.55 g/50 ml of acetone) and 1.0 ml of buffer
solution (1.0 g of potassium hydrogen phthalate/100 ml of
water). The flask was kept at 85 °C in a water bath for
2-{N,N-bis(20-chloroethyl)}aminoacetamido-5-
nitrobenzophenone (5d)
Yield = 54 %, red oil. Rf: 0.71 (ethyl acetate). IR KBr
(cm21): 3,329 (N–H), 3,091, 2,952 (C–H), 1,689 (C=O),
123