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1593 (CC), 1573 (CC), 1501 (NO2) cm−1; HRMS MH+ calcd
and washed with 3 × 25 mL of H2O, brine, then again with H2O to
remove excess DMF. The organic layer was then dried over MgSO4,
and the solvent was removed under reduced pressure. The crude
product was purified by column chromatography using a gradient of
EA/petroleum ether as the eluent to give the desired product 10d as a
red oil (0.065 g, 56%): 1H NMR (300 MHz, CDCl3) δ 7.57 (1H, dd, J
= 8.0, 1.7 Hz), 7.40 (1H, ddd, J = 8.7, 7.2, 1.6 Hz), 7.24 (1H, dd, J =
15.4, 1.4 Hz), 7.21 (1H, dd, J = 14.8, 1.7 Hz), 7.06 (1H, dd, J = 8.1, 1.5
Hz), 7.02−6.87 (6H, m), 6.76 (1H, dd, J = 8.2, 1.7 Hz), 3.77 (2H, t, J
= 8.1 Hz), 3.31 (3H, s), 1.6 (2H, m), 1.29 (2H, m), 0.90 (3H, t, J =
7.4, 7.1 Hz); 13C NMR (75 MHz, CDCl3) δ 146.7, 132.8, 132.3, 131.0,
130.1, 128.4, 128.3, 127.8, 127.5, 126.3, 125.9, 125.8, 124.1, 124.0,
123.7, 120.7, 120.6, 119.1, 49.8, 38.6, 29.0, 20.1, 14.0 IR (CDCl3) 2958
(C−H), 2929 (C−H), 2871 (C−H), 2817 (C−H), 1524 (NO2) cm−1;
HRMS MH+ calcd for C23H25N3O2Cl 410.1630, found 410.1640.
N1-Butyl-N2-(2-fluorophenyl)-N2-methyl-N1-(2-nitrophenyl)-
benzene-1,2-diamine (10e). A solution of the fluoro nitroaryl
derivative 9b (0.102 g, 0.300 mmol) in 2 mL of DMF was added to
KH (0.121 g, 0.910 mmol). Upon addition, the solution went from
orange to deep purple. The mixture was stirred at rt for 10 min. n-
Butyl bromide (0.32 mL, 3.0 mmol) was added dropwise via syringe.
The reaction was heated to 80 °C and stirred until the solution
returned to an orange color 3 h. The reaction was then quenched with
H2O and extracted with 3 × 15 mL DCM. The organic layers were
combined and washed with 3 × 25 mL H2O, with brine and then with
H2O again to remove excess DMF. The organic layer was then dried
over MgSO4, and the solvent was removed under reduced pressure.
The crude product was purified by column chromatography using a
gradient of EA/petroleum ether as the eluent to produce the N1-
for C19H17N3O2F 338.1299, found 338.1306.
N1-Methyl-N2-(2-nitrophenyl)-N1-phenylbenzene-1,2-dia-
mine (9c). Nor-halo aniline derivative 8c (0.163 g, 2.5 mmol), o-
iodonitrobenzene (0.249 g, 2.50 mmol), Pd(dba)2 (0.072 g, 5% mol),
BINAP (0.112 g, 7.5% mol), Cs2CO3 (0.900 g, 2.75 mmol), and 5 mL
of toluene were placed in a pressure tube. The mixture was purged
with argon at rt for 15 min. The pressure tube was then sealed and
placed in a preheated oil bath at 120 °C for 36 h. When TLC showed
consumption of 8c, the reaction mixture was filtered through a pad of
silica gel eluting with 90/10 EA/CH2Cl2. The solvent was removed
under reduced pressure and the resulting product was purified by
column chromatography eluting with 10/90 EA/petroleum ether to
afford the desired dimethyl derivative 9c as a yellow gum (0.163 g,
1
70% yield): H NMR (300 MHz, CDCl3) δ 9.24 (1H, s), 8.08 (1H,
dd, J = 9.9, 1.8 Hz), 7.47−7.43 (1H, m), 7.34−7.20(5H, m), 7.11 (2H,
dt, J = 6.4, 1.0 Hz), 6.74 (2H,ddd, J = 7.5, 7.9, 1.2 Hz), 6.65 (1H, d, J =
1.0 Hz), 6.62 (1H, d, J = 1.0 Hz), 3.23 (3H, s); 13C NMR (75 MHz,
CDCl3) δ 148.6, 142.1, 141.8, 135.6, 135.12, 133.9, 129.0, 127.8,
126.6, 126.0, 125.9, 123.7, 119.1, 117.7, 116.1, 115.1, 39.6; HRMS
MH+ calcd for C19H18N3O2 320.1394, found 320.1394.
N1-(2-Fluorophenyl)-N1,N2-dimethyl-N2-(2-nitrophenyl)-
benzene-1,2-diamine (10b). A solution of fluoro nitroaryl
derivative 9b (0.082 g, 0.24 mmol) in 2 mL of DMF was added to
KH (0.100 g, 0.72 mmol, freshly washed with petroleum ether). Upon
addition, the solution changed color from orange to deep purple. The
mixture was stirred at rt for 10 min, then methyl iodide (1.0 mL, 1.2
mmol) was added dropwise via syringe. Stirring was continued until
the solution became bright yellow in color (2 h). The reaction was
then quenched with H2O and extracted with 3 × 10 mL 90/10 EA/
CH2Cl2. The organic layers were combined and washed with 3 × 20
mL H2O and then brine. The organic layer was dried over Na2SO4,
and the solvent was removed under reduced pressure to give the
desired N1,N2-dimethyl derivative 10b as a yellow solid (0.082 g, 97%
yield): 1H NMR (500 MHz, CDCl3) δ 7.62 (1H, dd, J = 8.2, 1.7 Hz),
7.34 (1H, ddd, J = 8.8, 7.4, 1.9 Hz), 7.1−6.75 (10H, m), 3.22 (3H, s),
3.14 (3H, s); 13C NMR (125 MHz, CDCl3) δ 155.1 (d, J = 148 Hz),
143.0, 143.8, 140.9, 137.6, 132.9, 132.6 (d, J = 25 Hz), 125.9, 125.8,
125.6, 125.1, 125.0, 124.4 (d, J = 2 Hz), 122.1 (d, J = 5 Hz), 121.7,
121.5 (d, J = 2 Hz), 120.0, 116.5 (d, J = 12 Hz), 40.1, 39.2; IR
(CDCl3) 1606 (CC), 1591 (CC), 1568 (CC), 1522 (NO2),
1500 (NO2) cm−1; HRMS (M + H)+ calcd for C20H19N3O2F
352.1456, found 352.1463.
1
methyl-N2-butyl derivative 10e as a red oil (0.063 g, 53%): H NMR
(300 MHz, CDCl3) δ 7.57 (1H, dd, J = 8.1, 1.5 Hz), 7.34 (1H, ddd, J
= 8.7, 7.3, 1.7 Hz), 7.11−6.77 (9H, m), 3.59 (2H, t, J = 15.9, 8.0 Hz),
3.06 (3H, s), 1.65−1.54 (2H, m), 1.30 (2H, s, J = 7.3 Hz), 0.88 (3H, t,
J = 7.3 Hz); 13C NMR (75 MHz, CDCl3) δ 154.4 (d, J = 255 Hz),
141.8, 141.0, 137.5, 132.6, 132.3, 132.0, 130.1, 129.3 (d, J = 30 Hz),
128.3, 127.8, 125.8, 125.6, 125.1, 124.1, 122.6, 121.3, 120.8, 120.3,
116.3 (d, J = 22 Hz), 52.5, 39.2, 29.7, 20.3, 13.9; HRMS MH+ calcd for
C23H25N3O2F 394.1925, found 394.1939.
N1-Butyl-N2-methyl-N1-(2-nitrophenyl)-N2-phenylbenzene-
1,2-diamine (10f). Nitro triaryl compound 9c (735 mg, 2.30 mmol)
was placed in a round-bottom flask, and 12 mL of anhydrous DMF
was added. To that solution was added powdered KOH (593 mg, 10.6
mmol) and the reaction mixture stirred for 10 min at rt. Then, n-butyl
bromide (3.21 g, 23.4 mmol) was added neat, and the reaction mixture
was heated in an 80 °C oil bath for 3 h. The reaction mixture was then
cooled to rt, diluted with 20 mL water, and extracted 3 × with diethyl
ether. The organic extracts were combined, dried over MgSO4, and
filtered and the filtrate concentrated to dryness to give the N-butyl
derivative 10f as a brown oil that was carried on directly without
further purification.
N1,N2-Dimethyl-N1-(2-nitrophenyl)-N2-phenylbenzene-1,2-
diamine (10c). To a solution of aniline 9c (0.163 g, 2.0 mmol) in
DMF (10 mL) at rt was added freshly crushed KOH (0.504 g, 9
mmol). After 10 min, MeI (0.40 mL, 6 mmol) was added to the
stirring mixture dropwise via syringe. Stirring was continued at rt until
TLC showed consumption of the aniline starting material. The
reaction was then quenched with 25 mL deionized water and extracted
with 3 × 30 mL of EA. The organic layers were combined and dried
over MgSO4. The solvent was removed under reduced pressure to
provide the nor-halo N,N′-dimethyl derivative 10c as a brown oil
(0.170 g, 100% yield): 1H NMR (300 MHz, CDCl3) δ 7.59 (1H, dd, J
= 8.2, 1.6 Hz), 7.29−7.15 (3H, m), 7.11−7.04 (4H, m), 6.92 (1H, dt, J
= 7.2, 1.2 Hz), 6.76 (1H, dd, J = 8.2, 1.2 Hz), 6.72 (1H, dt, J = 13.5,
1.2 Hz), 6.34 (1H, d, J = 3.2 Hz), 6.31 (1H, d, J = 1.9 Hz), 3.27 (3H,
s), 2.82 (3H, s); 13C NMR (75 MHz, CDCl3) δ 147.8, 144.1, 143.5,
142.9, 140.1, 132.8, 129.0, 128.4, 126.5, 125.3, 124.7, 124.4, 123.6,
121.5, 117.5, 113.9, 41.2, 38.1; HRMS MH+ calc for C20H20N3O2
334.1550, found 334.1547.
N1-Methyl-N2-(2-(methylamino)phenyl)-N1-phenylbenzene-
1,2-diamine (15c). A round-bottom flask was charged with 30% KH
(187 mg, 1.4 mmol), and the solid was washed under nitrogen
atmosphere with 3 × 5 mL portions of petroleum ether. The solid was
then suspended in 1 mL anhydrous THF and stirred at RT while
diisopropylamine (50.0 μL, 0.356 mmol) was added. Stirring at
ambient temperature was continued for 10 min before N,N′-dimethyl
triaryl derivative 3c (30 mg, 0.10 mmol) was added as a solution in 1
mL of THF. The reaction mixture was then heated and maintained at
reflux for 2 h and then cooled to rt. The reaction mixture was diluted
with water and extracted 2× with ethyl acetate. The organic extracts
were combined, dried over MgSO4, and filtered, and the filtrate was
concentrated to dryness. The residue was dissolved in petroleum ether
and purified by passing the solution through silica gel eluting with
petroleum ether and then with 2% dichloromethane, 10% ether, 88%
petroleum ether. The purified material was concentrated to dryness to
N1-Butyl-N2-(2-chlorophenyl)-N2-methyl-N1-(2-nitrophenyl)-
benzene-1,2-diamine (10d). A solution of chloro N1-methylaniline
derivative 9a9 (0.100 g, 0.28 mmol) in 2 mL of DMF was added to KH
(0.112 g, 0.830 mmol). Upon addition, the solution went from orange
to deep purple. The mixture was stirred at rt for 10 min. n-Butyl
bromide (0.30 mL, 2.8 mmol) was added dropwise via syringe. The
reaction was warmed to 80 °C and stirred until the solution returned
to an orange color (3 h). The reaction was then quenched with H2O
and extracted with 3 × 15 mL EA. The organic layers were combined
1
give the product 15c as a clear gum (26.8 mg, 89%): H NMR (500
MHz, CDCl3) δ 7.23 (2H, t, J = 7.5 Hz), 7.13−7.07 (4H, m), 6.80
(2H, t, J = 7.5 Hz), 6.80 (2H, t, J = 7.5 Hz), 6.71 (2H, t, J = 4 Hz),
6.65 (3H, t, J = 3.0 Hz), 5.51 (1H,s), 4.06 (1H, bs), 3.29 (3H, s), 2.76
H
dx.doi.org/10.1021/jo302795w | J. Org. Chem. XXXX, XXX, XXX−XXX