EXPERIMENTAL
PMR spectra were recorded in DMSO-d on a Bruker DRX500 spectrometer at frequency 500 MHz relative to TMS
6
internal standard. Mass spectra were recorded in a Finnigan Mat. Incos 50 instrument with direct sample introduction at
ionization energy 70 eV. Melting points were determined on a Boetius instrument. TLC was performed on Sorbfil plates with
detection by iodine vapor.
X-ray Structure Analysis. Cell constants and intensities of 3857 independent reflections were measured on a CCD
TM
Xcalibur R diffractometer (Oxford Diffraction) using Cu K -radiation, graphite monochromator, ω/2θ-scanning, and scan
α
°
range 6 ≤ θ ≤ 151.5°. Crystals were monoclinic (0.3 × 0.2 × 0.4 mm), a = 8.833(1), b = 7.596(1), c = 14.834(1)A,
β = 96.79(9)°, V = 988.37(18)A , Z = 2(C H Cl N O ), d
° 3
3
= 1.469 g/cm , space group P2 .
19 18
2
4
4
calc
1
A total of 3462 independent reflections with I > 2σ(I) was used in the calculations. The structure was solved by direct
methods and refined by anisotropic full-matrix least-squares methods for nonhydrogen atoms. H atoms were fixed geometrically
and refined by the riding model. Absorption corrections were applied using multi-scan. The final agreement factors were
2
2
2
R[F > 2σ(F )] = 0.0401, ωR(F ) = 0.1050. Atomic coordinates and geometric parameters were deposited in the Cambridge
Crystallographic Data Centre (CCDC 711612). All calculations were carried out using the SHELXL-97 programs.
2-Bromo-N-(2,6-dichloro-4-nitrophenyl)acetamide (4). A solution of 2,6-dichloro-4-nitroaniline (3.20 g,
0.0155 mol) in DMF (10 mL) was stirred by a magnetic stirrer, treated dropwise at room temperature with bromoacetic acid
bromide (3.17 g, 0.0157 mol), heated with constant stirring at 55–60°C for 3 h, left overnight, and poured into a beaker with
water (100 g) and ice (100 g). The resulting yellowish precipitate was filtered off, washed with water, and dried at 90°C to
afford 2 (4.78 g, 94%), mp 198–200°C (propanol-2), C H BrCl N O . PMR spectrum (500 MHz, DMSO-d , δ, ppm, J/Hz):
8
5
2
2
3
6
4.15 (2H, s, CH ), 8.40 (2H, s, H-Ar), 10.73 (1H, s, N–H).
2
2-Bromo-N-(2,6-dibromo-4-nitrophenyl)acetamide (5) was prepared analogously to 4 from 2,6-dibromo-4-
nitroaniline (5.92 g, 0.02 mol) and bromoacetic acid bromide (4.24 g, 0.021 mol) in 96% yield. Two recrystallizations from
2-propanol:EtOAc (1:1) gave mp 211–212°C, C H Br N O . PMR spectrum (500 MHz, DMSO-d , δ, ppm, J/Hz): 4.17 (2H,
8
5
3
2
3
6
s, CH ), 8.52 (2H, s, H-Ar), 10.62 (1H, s, N–H).
2
2-Bromo-N-(2,6-diiodo-4-nitrophenyl)acetamide (6) was prepared analogously to 4 from 2,6-diiodo-4-nitroaniline
(3.90 g, 0.01 mol) and bromoacetic acid bromide (2.22 g, 0.011 mol) in 91% yield. Recrystallization from 2-propanol:DMF
(1:1) gave mp 225–227°C, C H BrI N O . PMR spectrum (500 MHz, DMSO-d , δ, ppm, J/Hz): 4.15 (2H, s, CH ), 8.63 (2H,
8
5
2
2
3
6
2
s, H-Ar), 10.31 (1H, s, N–H).
N-(2′,6′-Dichloro-4′-nitrophenyl)-2-N-cytisinoacetamide (7). A suspension of 4 (0.71 g, 2.2 mmol) in anhydrous
toluene (10 mL) was treated with triethylamine (0.50 g, 5 mmol) and cytisine (0.42 g, 2.2 mmol) and refluxed with stirring for
3 h. The hot solution was filtered to remove the precipitate of triethylamine hydrobromide, which was washed several times
with hot benzene. The combined mother liquors were evaporated to afford a light-yellow crystalline compound (0.60 g, 63%),
+
mp 214–215°C (benzene:2-propanol, 5:1), C H Cl N O . Mass spectrum (EI, 70 eV, m/z, I , %): 437 (5) [M] , 203 (100),
19 18
2
4
4
rel
146 (27), 58 (98), 42 (43). PMR spectrum (500 MHz, DMSO-d , δ, ppm, J/Hz): 1.77 (2H, dd, J = 12.6, J = 12.7, H-8),
6
8,7
8,9
2.45 (1H, br.s, H-9), 2.60 (2H, m, H-11), 2.96 (1H, m, H-7), 3.06 (2H, m, H-13), 3.17 (2H, dd, J = 15.2, H-14), 3.75 (1H, m,
a,b
H-10a), 3.88 (1H, d, J
= 15.3, H-10e), 6.09 (1H, d, J = 6.8, H-5), 6.14 (1H, d, J = 9.0, H-3), 7.24 (1H, dd, J = 6.8,
10e,10a
5,4 3,4 4,5
J
= 9.0, H-4), 8.37 (2H, s, H-Ar), 9.45 (1H, s, N–H).
4,3
N-(2′,6′-Dibromo-4′-nitrophenyl)-2-N-cytisinoacetamide (8) was prepared analogously to 7 from 5 (1.60 g,
3.8 mmol) and cytisine (0.73 g, 3.8 mmol) in 79% yield. Recrystallization from 2-propanol:hexane (5:1) gave mp 195–197°C,
+
C H Br N O . Mass spectrum (EI, 70 eV, m/z, I , %): 524, 528 (3) [M] , 203 (100), 160 (33), 43 (32). PMR spectrum
19 18
2
4
4
rel
(500 MHz, DMSO-d , δ, ppm, J/Hz): 1.77 (2H, dd, J = 12.6, J = 12.7, H-8), 2.45 (1H, br.s, H-9), 2.61 (2H, m, H-11), 3.01
6
8,7
8,9
(1H, m, H-7), 3.08 (2H, m, H-13), 3.14 (2H, dd, J = 15.1, H-14), 3.77 (1H, m, H-10a), 3.91 (1H, d, J
= 15.2, H-10e),
a,b
10e,10a
6.10 (1H, d, J = 6.7, H-5), 6.13 (1H, d, J = 8.9, H-3), 7.24 (1H, dd, J = 6.7, J = 8.9, H-4), 8.48 (2H, s, H-Ar), 9.42 (1H,
5,4
3,4
4,5
4,3
s, N–H).
N-(2′,6′-Diiodo-4′-nitrophenyl)-2-N-cytisinoacetamide (9) was prepared analogously to 7 from 6 (0.51 g, 1 mmol)
and cytisine (0.19 g, 1 mmol) in 80% yield. Recrystallization from 2-propanol gave mp 241–242°C, C H I N O . Mass
19 18 2
4 4
spectrum (EI, 70 eV, m/z, I , %): 418 (23), 203 (100), 58 (71), 42 (27). PMR spectrum (500 MHz, DMSO-d , δ, ppm, J/Hz):
rel
6
1.80 (2H, dd, J = 12.8, J = 13.1, H-8), 2.45 (1H, br.s, H-9), 2.68 (2H, m, H-11), 3.04 (1H, m, H-7), 3.09 (2H, m, H-13),
8,7
8,9
3.12 (2H, s, H-14), 3.76 (1H, m, H-10a), 3.95 (1H, d, J
= 15.3, H-10e), 6.09 (1H, d, J = 6.3, H-5), 6.11 (1H, d,
10e,10a
5,4
J
= 8.4, H-3), 7.23 (1H, dd, J = 6.3, J = 8.4, H-4), 8.58 (2H, s, H-Ar), 9.30 (1H, s, N–H).
3,4
4,5 4,3
683