5662 Journal of Medicinal Chemistry, 2007, Vol. 50, No. 23
Zhan et al.
Hz), 6.71 (4H, d, J ) 7.8 Hz), 4.31 (4H, s), 3.48 (2H, br), 2.32
(12H, s); 13C NMR (100 MHz, CDCl3) δ 148.44, 134.94, 134.31,
129.53, 117.67, 112.73, 43.70, 16.52. m/z (EI+) calcd for C24H31N2,
344.7; found, 344.5 M+. Anal. Calcd for C24H31N2: C, 83.68; H,
8.19; N, 8.13. Found: C, 83.34; H, 8.09; N, 7.89.
N,N′-Diphenyl-9,10-anthracenedimethanamine (25b). The title
compound was prepared according to general procedure C as a
yellow solid in 98% yield. Rf ) 0.54 (4:1, hexane/ethyl acetate).
1H NMR (400 MHz, CDCl3) δ 8.36 (4H, dd, J ) 7.2 Hz, 3.2 Hz),
7.55 (4H, dd, J ) 7.2 Hz, 3.2 Hz), 7.32 (4H, t, J ) 8.0 Hz), 6.85
(6H, m), 5.20 (4H, s), 3.98 (2H, br); 13C NMR (150 MHz, CDCl3)
δ 148.51, 130.86, 130.53, 129.68, 126.50, 125.13, 118.15, 112.94,
41.34. HRMS calcd for C31H24N2, 388.19395; found, 389.20095
[M + H]+. Anal. Calcd for C31H24N2: C, 86.56; H, 6.23; N, 7.21.
Found: C, 86.35; H, 6.13; N, 6.82.
(0.77 mL, 8.4 mmol), and NaBH(OAc)3 (2.54 g, 12.0 mmol) with
HOAc (0.46 mL, 8.0 mmol), the modified general procedure C
delivered 30a (238.5 mg, 19%) as a pale white solid. Rf ) 0.44
1
(4:1, hexane/ethyl acetate). H NMR (400 MHz, CDCl3) δ 7.32
(4H, s), 7.11 (4H, t, J ) 7.8 Hz), 6.66 (2H, m), 6.52 (4H, m), 4.48
(2H, m), 4.01 (2H, s), 1.52 (3H, s), 1.50 (3H, s); 13C NMR (100
MHz, CDCl3) δ 147.51, 143.93, 143.96, 129.30, 126.35, 117.36,
117.35, 113.43, 53.31, 53.29, 25.01, 24.91. HRMS calcd for
C22H24N2, 316.19395; found, 317.20095 [M + H]+. Anal. Calcd
for C22H24N2: C, 83.50; H, 7.64; N, 8.85. Found: C, 83.05; H,
7.72; N, 8.68.
N,N′-Dimethyl-N,N′-diphenyl-1,4-benzenedimethanamine (30b).
Starting from 1,4-benzenedialdehyde (536.0 mg, 4.0 mmol), N-
methyl-benzenenamine (0.91 mL, 8.4 mmol), and NaBH(OAc)3
(2.54 g, 12.0 mmol), general procedure C delivered the title
compound 30b (1.18 g, 93%) as a pale white solid. Rf ) 0.69 (4:1,
N,N′-Diphenyl-1,3-benzenedimethanamine (25c).54 From m-
phthalaldehyde (536.0 mg, 4.0 mmol), aniline (0.77 mL, 2.1 mmol),
and NaBH(OAc)3 (2.54 g, 12.0 mmol), general procedure C
delivered 22c (1.02 g, 88%) as a pale yellow solid. Rf) 0.57 (4:1,
hexane/ethyl acetate). 1H NMR (400 MHz, CDCl3) δ 7.43 (1H, s),
7.36 (3H, m), 7.23 (4H, m), 6.78 (2H, t, J ) 7.8 Hz), 6.68 (4H, d,
J ) 7.8 Hz), 4.36 (4H, s), 4.07 (2H, s); 13C NMR (100 MHz,
CDCl3) δ 148.26, 140.09, 129.44, 129.03, 126.74, 126.54, 117.77,
113.05, 48.42. m/z (EI+) calcd for C20H20N2, 318.5; found, 318.4.
Anal. Calcd for C20H20N2: C, 83.30; H, 6.99; N, 9.71. Found: C,
83.31; H, 6.95; N, 9.70.
1
hexane/ethyl acetate). H NMR (400 MHz, CDCl3) δ 7.24 (4H,
m), 7.19 (4H, s), 6.75 (6H, m), 4.53 (4H, s), 3.02 (6H, s); 13C NMR
(100 MHz, CDCl3) δ 149.90, 137.83, 129.35, 127.16, 116.69,
112.52, 56.53, 38.69. HRMS calcd for C22H24N2, 316.19395; found,
317.20085 [M + H]+. Anal. Calcd for C22H24N2: C, 83.50; H, 7.64;
N, 8.85. Found: C, 83.36; H, 7.63; N, 8.87.
N,N′-Bis[2-(phenylamino)ethyl]-1,4-benzenedimethanamine
(30c). The title compound was prepared according to general
procedure C as a pale white solid in 56% yield. Rf ) 0.66 (3:1,
CH2Cl2/MeOH). 1H NMR (600 MHz, CDCl3) δ 7.29 (4H, s), 7.18
(4H, t, J ) 5.2 Hz), 6.71 (2H, t, J ) 4.8 Hz), 6.64 (4H, d, J ) 6
Hz), 4.12 (2H, br), 3.81 (4H, s), 3.23 (4H, t, J ) 3.6 Hz), 2.91
(4H, t, J ) 3.6 Hz); 13C NMR (100 MHz, CDCl3) δ 148.64, 139.18,
129.38, 131.36, 117.53, 113.13, 53.49, 48.17, 43.65. mp 42-43
°C. HRMS calcd for C24H30N4, 374.24705; found, 375.25391 [M
+ H]+. A salt form of 30c was prepared as a white solid for the
elemental analysis. Anal. Calcd for C24H30N4‚2HCl: C, 64.42; H,
7.21; N, 12.52. Found: C, 64.32; H, 7.21; N, 12.30.
2,5-Dimethyl-N,N′-diphenyl-1,4-benzenedimethanamine (26a).55
2,5-Bis(chloromethyl)-p-xylene (406.2 mg, 2.0 mmol) and aniline
(0.38 mL, 4.2 mmol) in absolute ethanol (15 mL) with pyridine
(0.81 mL, 10 mmol) were heated to reflux overnight. The solvent
was removed to minimum volume, followed by addition of ethyl
acetate (15 mL). The resulting mixture was washed with brine and
dried over MgSO4. Removal of the solvent gave the crude product
which was purified by column chromatography to give 26a (433.5
mg, 68%) as a pale yellow solid. Rf ) 0.54 (4:1, hexane/ethyl
acetate). 1H NMR (400 MHz, CDCl3) δ 7.21 (6H, m), 6.76 (2H, t,
J ) 7.2 Hz), 6.67 (4H, d, J ) 8.0 Hz), 4.24 (4H, s), 3.90 (2H, br),
2.32 (6H, s); 13C NMR (100 MHz, CDCl3) δ 148.42, 136.25,
134.21, 130.85, 129.50, 117.82, 113.04, 46.44, 18.68. m/z (EI+)
calcd for C22H24N2, 316.5; found, 316.4 M+. Anal. Calcd for
C22H24N2: C, 83.50; H, 7.64; N, 8.85. Found: C, 83.46; H, 7.38;
N, 9.01.
N,N′-Bis(phenylmethyl)-1,4-benzenedimethanamine (30d).57
Starting from 1,4-benzenedialdehyde (536.0 mg, 4.0 mmol), ben-
zenemethanamine (0.92 mL, 8.4 mmol), and NaBH(OAc)3 (2.54
g, 12.0 mmol), general procedure C delivered the title compound
30d (852.8 mg, 67%) as a pale yellow solid. Rf ) 0.69 (ethyl acetate
1
with 2% NH4OH). H NMR (600 MHz, DMSO-d6) δ 7.32 (8H,
m), 7.31 (4H, s), 7.22 (2H, tt, J ) 7.2 Hz, 1.2 Hz), 3.66 (4H, s),
3.65 (4H, s), 2.53 (2H, s); 13C NMR (100 MHz, DMSO-d6) δ
140.44, 139.12, 131.49, 131.33, 131.26, 127.04, 53.24, 53.00.
HRMS calcd for C22H24N2, 316.19395; found. 317.20083 [M +
H]+. Anal. Calcd for C22H24N2: C, 83.50; H, 7.64; N, 8.85.
Found: C, 83.49; H, 7.72; N, 8.80.
N,N′-Diphenyl-1,2-benzenedimethanamine (26b). To a solution
of aniline (1.8 mL, 20 mmol) and pyridine (1.62 mL, 20 mmol) in
absolute ethanol (10 mL) was added dropwise a solution of
o-xylylene dibromide (527.9 mg, 2.0 mmol) in ethanol (10 mL) at
-20 °C. The reaction mixture was stirred at -20 °C for 24 h, at
which point the solvent was removed to minimum volume followed
by addition of ethyl acetate (15 mL). The resulting mixture was
washed with brine and dried over MgSO4. Removal of the solvent
gave the crude product which was purified by column chromatog-
raphy to give 26b (333.5 mg, 58%) as a white solid. Rf ) 0.53
N,N′-Bis(4-cyanylphenyl)-1,4-benzenedimethanamine (31a).
The title compound was prepared according to general procedure
C as a pale white solid in 57% yield. Rf ) 0.25 (1:1, hexane/ethyl
1
acetate). H NMR (400 MHz, DMSO-d6) δ 7.42 (4H, d, J ) 9.2
Hz), 7.29 (4H, s), 7.26 (2H, t, J ) 6.0 Hz), 6.63 (4H, d, J ) 9.2
Hz), 4.30 (4H, d, J ) 6.0 Hz); 13C NMR (100 MHz, DMSO-d6) δ
152.04, 137.68, 133.31, 127.31, 120.54, 112.22, 95.88, 45.41. m/z
(EI+) calcd for C22H18N4, 338.4; found, 338.5 M+. Anal. Calcd for
C22H18N4: C, 78.08; H, 5.36; N, 16.56. Found: C, 77.84; H, 5.38;
N, 16.17.
1
(4:1, hexane/ethyl acetate). H NMR (600 MHz, CDCl3) δ 7.44
(2H, m), 7.30 (2H, m), 7.19 (4H, tt, J ) 6.6 Hz, 1.8 Hz), 6.77 (2H,
t, J ) 7.8 Hz), 6.68 (4H, d, J ) 7.8 Hz), 4.60 (2H, br), 4.40 (4H,
s); 13C NMR (100 MHz, CDCl3) δ 148.13, 137.44, 129.56, 129.51,
131.17, 118.21, 113.41, 46.55. HRMS calcd for C20H20N2, 318.16265;
found, 319.16957 [M + H]+. Anal. Calcd for C20H20N2: C, 83.30;
H, 6.99; N, 9.71. Found: C, 83.32; H, 6.97; N, 9.72.
N,N′-Bis(4-nitrophenyl)-1,4-benzenedimethanamine (31b). The
title compound was prepared according to general procedure C as
a yellow solid in 62% yield. Rf ) 0.24 (1:1, hexane/ethyl acetate).
1H NMR (400 MHz, DMSO-d6) δ 7.97 (4H, d, J ) 9.2 Hz), 7.88
(2H, t, J ) 5.6 Hz), 7.33 (4H, s), 6.66 (4H, d, J ) 9.2 Hz), 4.39
(4H, d, J ) 5.6 Hz); 13C NMR (100 MHz, DMSO-d6) δ 154.40,
137.42, 135.86, 127.42, 126.14, 45.50. HRMS calcd for C20H18N4O4,
378.18231; found, 379.13980 [M + H]+. Anal. Calcd for
C20H18N4O4: C, 63.48; H, 4.79; N, 14.81. Found: C, 63.53; H,
4.91; N, 14.76.
N,N′-Bis(3-fluorophenyl)-1,4-benzenedimethanamine (31g).
The title compound was prepared according to general procedure
C as a white solid in 62% yield. Rf ) 0.35 (4:1, hexane/ethyl
acetate). 1H NMR (400 MHz, CDCl3) δ 7.35 (4H, s), 7.10 (2H, q,
J ) 8.4 Hz), 6.44-6.39 (4H, m), 6.32 (2H, dt, J ) 11.6 Hz, 2.4
N,N′,N′′-Triphenyl-1,3,5-benzenetrimethanamine (29). Start-
ing from trimesoyl chloride, the modified general procedure D
provided the title compound 29 as a pale yellow solid in 80% yield
(2 steps). Rf ) 0.74 (2:1, hexane/ethyl acetate). 1H NMR (400 MHz,
CDCl3) δ 7.31(3H, s); 7.18 (6H, m), 6.74 (3H, tt, J ) 7.2 Hz, 0.8
Hz), 6.63 (6H, m), 4.32 (6H, s), 4.03 (3H, s); 13C NMR (100 MHz,
CDCl3) δ148.24, 140.60, 129.44, 125.66, 117.84, 113.10, 48.42.
m/z (EI+) calcd for C27H27N3 393.5; Found 393.5. Ana. Calcd for
C27H27N3: C, 82.41; H, 6.92; N, 10.68; Found: C, 81.99; H, 6.86;
N, 10.40.
R,R′-Dimethyl-N,N′-diphenyl-1,4-benzenedimethanamine(30a).56
Starting from 1,4-diacetylbenzene (648.8 mg, 4.0 mmol), aniline