Manka et al.
3a , X ) Br (0.15 g, 73% yield) as a colorless oil: 1H NMR δ
0.86 (t, J ) 7.3 Hz, 6H), 1.48 (sextet, J ) 7.3 Hz, 4H), 2.78-
2.73 (m, 4H), 3.96 (br s, 4H), 7.79 (s, 2H); 13C NMR δ 13.3,
22.8, 38.2, 109.8, 118.6, 129.3, 135.8, 136.3, 141.5; IR 3477 and
146.9, 147.8; IR 1529 and 1350 (NO2) cm-1; EI-MS m/z 433,
431, 429 (M, 0.5:1:0.5), 264 and 262 (100:100). Anal. Calcd for
C
15H13Br2NO2S: C, 41.79; H, 3.04; Br, 37.07; N, 3.25; S, 7.44.
Found: C, 41.88; H, 3.07; Br, 36.95; N, 3.17; S, 7.52.
3378 (N-H), 1602 (CdC) cm-1. Anal. Calcd for C18H20
-
2-Am in o-3,5-d ibr om o-2′-p r op ylth iobip h en yl (9). A mix-
ture of nitrobiphenyl 8 (3.11 g, 7.20 mmol), Zn powder (2.35
g, 36.0 mmol), and AcOH (30 mL) was stirred overnight at
room temperature. The reaction mixture was filtered to remove
solids, and the solids were washed with CH2Cl2. Water was
added to the filtrate, and CH2Cl2 was used to extract the
organic products. Dilute HCl was added at this stage to
dissolve the emulsion. The extract was washed with NaHCO3
solution and dried (Na2SO4), and the solvent was removed. The
yellow oil was purified by column chromatography (CH2Cl2:
hexanes, 2:1) to give amine 9 (2.42 g, 84% yield) as a light
yellow liquid: 1H NMR δ 0.79 (t, J ) 7.3 Hz, 3H), 1.35 (sextet,
J ) 7.3 Hz, 2H), 2.46-2.58 (m, 2H), 3.54 (br s, 2H), 6.74-6.83
(m, 2H), 6.98 (d, J ) 7.6 Hz, 1H), 7.14-7.22 (m, 1H), 7.41 (d,
J ) 2.5 Hz, 1H), 7.82 (d, J ) 2.0 Hz, 1H); 13C NMR δ 13.1,
22.6, 37.8, 115.5, 118.0, 122.5, 126.2, 129.2, 129.8, 130.7, 132.3,
133.2, 135.0, 143.3, 147.3; IR 3471 and 3382 (N-H), 1617 (Cd
C) cm-1; EI-MS, m/z 405, 403, 401 (M, 19:39:20), 326 (100).
Anal. Calcd for C15H15Br2NS: C, 44.91; H, 3.77; Br, 39.84; N,
3.49; S, 7.99. Found: C, 45.00; H, 3.80; Br, 39.75; N, 3.49; S,
7.96.
2-Acetyla m in o-3,3′,5,5′-tetr a br om o-2′-p r op ylth iobip h e-
n yl (10, X ) Br ). A mixture of biphenyl 1a , X ) Br (30 mg,
0.05 mmol) and Ac2O (1 mL) in benzene (5 mL) was refluxed
overnight. Benzene was removed and the residue was purified
by column chromatography (CH2Cl2) to give 10, X ) Br (24
mg, 74% yield) as a brown oil: 1H NMR δ 0.79 (t, J ) 7.3 Hz,
3H), 1.24-1.38 (m, 2H), 1.92 (s, 3H), 2.44-2.62 (m, 2H), 6.92
(s, 1H), 7.34 (d, J ) 1.9 Hz, 1H), 7.42 (d, J ) 1.9 Hz, 1H),
7.83-7.84 (m, 2H); IR 3239 (N-H), 1666 (CdO) cm-1; EI-MS
m/z 601 (M, 4), 43 (100).
Br4N2S2: C, 33.36; H, 3.11; N, 4.32. Found: C; 33.70; H, 3.15;
N, 4.33.
3,3′,5,5′-Tetr a ch lor o-2,2′-d in itr o-6,6′-bis(p r op ylth io)bi-
p h en yl (3b, X ) Cl). A mixture of halide 32 (96 mg, 0.3 mmol),
freshly prepared Cu powder (60 mg, 0.9 mmol), and dry xylenes
(4 mL) was stirred overnight at 130 °C under N2. The reaction
was cooled and flushed through a silica gel plug (CH2Cl2:
hexanes, 1:1). The solvent was removed and the residue was
separated on a silica gel column (CH2Cl2:hexanes, 1:3) to give
3b, X ) Cl (42 mg, 57% yield) as a white solid: mp 130-131
1
°C; H NMR δ 0.93 (t, J ) 7.4 Hz, 6H), 1.58 (sextet, J ) 7.4
Hz, 4H), 2.84 (dt, J 1 ) 11.2 Hz, J 2 ) 7.4 Hz, 2H), 2.96 (dt, J 1
) 11.2 Hz, J 2 ) 7.4 Hz, 2H), 7.73 (s, 2H); 13C NMR δ 13.3,
22.6, 38.1, 126.4, 132.5, 135.2, 137.2, 143.1, 146.3; IR 1537 and
1355 (NO2) cm-1; EI-MS m/z 482 (M - NO2, 73), 369 (100),
367 (98); HRMS (FAB+) calcd for C18H17Cl4N2O4S2 528.9384,
found 528.9380. Anal. Calcd for C18H16Cl4N2O4S2: C, 40.77;
H 3.04; N, 5.28. Found: C, 40.97; H, 3.05; N, 5.32.
2-Am in o-3,5-dibr om o-3′,5′-dich lor o-6-n itr o-2′,6′-bis(pr o-
p ylth io)bip h en yl (4a , X ) Br , X′ ) Cl). A 0.5 M solution of
Br2 in AcOH (4.4 mL, 2.2 mmol) was added dropwise to
aminobiphenyl 48 (431 mg, 1.0 mmol) dissolved in AcOH (5
mL). After 3 h, the mixture was worked up as described for
3a , and the crude product was purified by column chromatog-
raphy (CH2Cl2:hexanes, 3:2) to give 4a , X ) Br, X′ ) Cl (528
mg, 90% yield) as a yellow solid: mp 158-159 °C; 1H NMR δ
0.91 (t, J ) 7.3 Hz, 6H), 1.53 (sextet, J ) 7.3 Hz, 4H), 2.78
(dt, J 1 ) 11.4 Hz, J 2 ) 7.3 Hz, 2H), 2.88 (dt, J 1 ) 11.4 Hz, J 2
) 7.3 Hz, 2H), 4.06 (br s, 2H), 7.67 (s, 1H), 7.78 (s, 1H); 13C
NMR δ 13.3, 22.7, 37.9, 99.6, 110.6, 121.5, 132.4, 135.6, 141.3,
141.8, 143.5, 148.7; IR 3474 and 3373 (N-H), 1612 and 1442
(CdC), 1532 and 1369 (NO2) cm-1. Anal. Calcd for C18H18Br2-
Cl2N2O2S2: C, 36.69; H, 3.08; N, 4.75. Found: C, 36.83; H,
3.06; N, 4.74.
3,5-Dibr om o-2-n it r o-2′-p r op ylt h iob ip h en yl (8). Pow-
dered amine 6 (15.35 g, 41.49 mmol) was slowly added with
stirring to concentrated HCl (100 mL). After 30 min, water
(50 mL) was added, and the resulting suspension was cooled
in an ice bath. A solution of NaNO2 (3.06 g, 44.3 mmol) in
water (20 mL) was added dropwise at a temperature below 5
°C. The resulting green solution was stirred in the ice bath
for 45 min, and then a cold 40% solution of NaOAc was added
to adjust the pH of the solution to 4-5. A few crystals of NiCl2
were added, followed by a solution of EtOCSSK (6.8 g, 42.5
mmol) in water (20 mL). A yellow precipitate immediately
formed, which turned brown as the suspension was slowly
warmed to room temperature. The resulting brown viscous
organic product was dissolved in CH2Cl2. The organic phase
was separated, dried, and flushed through a silica gel plug
(CH2Cl2). The filtrate was evaporated to dryness, and the
resulting crude xanthate 7 was used without further purifica-
tion for the alkylation step.
A solution of NaOH (2.00 g, 50 mmol) in MeOH (100 mL)
was added to the crude xanthate 7, and after 30 min,
1-iodopropane (9.0 mL, 92.3 mmol) was added. The reaction
mixture was stirred for 25 h at 70 °C until no xanthate
remained by GC/MS. Water was added, the organic products
extracted (CH2Cl2), and the extracts dried (Na2SO4), passed
through a silica gel plug (CH2Cl2), and partially decolorized
with charcoal. The solvent was removed leaving 8 (13.78 g,
77% yield based on amine 6) as a brown oil: 1H NMR δ 0.76
(t, J ) 7.3 Hz, 3H), 1.26-1.41 (m, 2H), 2.46 (dt, J 1 ) 12.1 Hz,
J 2 ) 7.2 Hz, 1H), 2.65 (dt, J 1 ) 12.1 Hz, J 2 ) 7.1 Hz, 1H), 7.29
(dd, J 1 ) 7.4 Hz, J 2 ) 1.1 Hz, 1H), 7.37 (d, J ) 8.3 Hz, 1H),
7.54-7.59 (m, 1H), 7.64-7.69 (m, 1H), 7.84 (d, J ) 2.1 Hz,
1H), 8.13 (d, J ) 7.8 Hz, 1H); 13C NMR δ 13.1, 22.5, 37.9, 122.4,
124.4, 129.1, 129.7, 131.0, 132.1, 132.5, 132.9, 133.9, 135.4,
2-Acetyla m in o-3′,5′-d ibr om o-3,5-d iiod o-2′-p r op ylth io-
bip h en yl (10, X ) I). Amine 1a , X ) I (1.00 g, 1.53 mmol)
was dissolved in pyridine (20 mL). Acetyl chloride (1.20 mL,
17 mmol) was added dropwise, immediately forming a pre-
cipitate. After being stirred overnight, the reaction mixture
was passed through a silica gel plug (CH2Cl2), eluent washed
with 1 M HCl, dried, and evaporated to give 2.33 g of a tan
sticky solid. The crude product was purified by column
chromatography (CH2Cl2:hexanes, 2:1) to give 10, X ) I (0.97
1
g, 91% yield) as a white powdery solid: mp 174-175 °C; H
NMR δ 0.79 (t, J ) 7.3 Hz, 3H), 1.24-1.40 (m, 2H), 1.91 (s,
3H), 2.43-2.61 (m, 2H), 6.89 (s, 1H), 7.40 (d, J ) 2.1 Hz, 1H),
7.54 (d, J ) 1.8 Hz, 1H), 7.82 (d, J ) 2.0 Hz, 1H), 8.25 (d, J )
1.6 Hz, 1H); 13C NMR δ 13.1, 22.5, 23.2, 38.1, 92.8, 101.6,
122.7, 131.8, 132.7, 132.9, 135.8, 137.0, 138.9, 141.7, 146.0,
146.8, 167.9; IR (KBr) 3219 (N-H), 1664 (CdO) cm-1. Anal.
Calcd for C17H15Br2I2NOS: C, 29.38; H, 2.18; N, 2.02. Found:
C, 28.85; H, 2.08; N, 1.93.
2-Dia cet yla m in o-3,3′,5,5′-t et r a br om o-2′-p r op ylt h iob i-
p h en yl (11, X ) Br ). 11, X ) Br was obtained quantitaively
as described for for 10, X ) Br, using catalytic amounts of
concentrated H2SO4. An analytically pure sample of 11, X )
Br was obtained by column chromatography (CH2Cl2:hexanes,
2:1): 1H NMR δ 0.98 (t, J ) 7.2 Hz, 3H), 1.61 (sextet, J ) 7.3
Hz, 2H), 2.03 (s, 3H), 2.43 (s, 3H), 2.81-2.93 (m, 2H), 7.27 (s,
1H), 7.44 (s, 1H), 7.85 (s, 1H), 7.90 (s, 1H); 13C NMR δ 13.4,
22.4, 25.4, 26.5, 39.0, 122.2, 122.4, 125.6, 129.7, 131.4, 133.0,
133.8, 135.6, 135.7, 136.5, 142.2, 143.9, 171.0, 173.0; IR 1723
(CdO) cm-1
.
2-Dia ce t yla m in o-3′,5′-d ib r om o-3,5-d iiod o-2′-p r op yl-
th iobip h en yl (11, X ) I). Amine 1a , X ) I (2.24 g, 3.6 mmol)
was dissolved in dry benzene (100 mL). Pyridine (0.60 mL)
was added followed by acetyl chloride (1.8 mL), and the
reaction was stirred overnight at 50 °C. Volatiles were removed
under vacuum. The residue was redissolved in CH2Cl2 and
passed through a silica gel plug. The solvent was evaporated
to yield 2.47 g of a brown oil that was purified by column
9584 J . Org. Chem., Vol. 68, No. 25, 2003