190
Vol. 49, No. 2
Experimental
C18H14N4O2: C, 67.92; H, 4.43; N, 17.60. Found: C, 68.01; H, 4.62; N,
Melting points were measured on a Yanagimoto micro melting points hot 17.81.
stage apparatus and are uncorrected. Infrared spectra (IR) were determined
7-Benzyl-1-butyl-3-phenylxanthine (8) The mixture of 3-phenylxan-
with a Horiba FT-720 spectrometer. Nuclear magnetic resonance spectra thine (7, 200 mg, 0.629 mmol), anhydrous K2CO3 (130 mg, 0.944 mmol) and
(1H-NMR) was recorded on a JEOL EX 90A spectrometer. Chemical shifts n-butyl bromide (129 mg, 0.944 mmol) in DMF (5 ml) was stirred overnight
are quoted in parts per million (ppm) with tetramethyl silane as an internal at 60 °C. The reaction mixture was concentrated in vacuo, the residue was
standard, and coupling constants (J) are given in hertz (Hz). Microanalyses chromatogaraphed on silica gel using CHCl3–MeOH (6 : 1) as an eluent to
were performed in the Micro Analytical Laboratory of this faculty. Yield and give 8 (175.6 mg, 75%). mp 139—140 °C (AcOEt–MeOH). 1H-NMR
physicochemical data of the 6-hydroxyalkylamino-3-phenylxanthines (11a,
(CDCl3) d: 0.96 (3H, t, Jϭ7.5 Hz), 1.21—1.85 (4H, m), 4.06 (2H, t,
b, d, e) and the 4-phenyl[i]condensed-purine (4a, b, d, e) are summarized in Jϭ7.5 z), 7.37—7.61 (10H, m), 7.65 (1H, s). IR (KBr) cmϪ1: 1714, 1672.
Table 2 and 3, respectively.
7-Propyl-3-phenylxanthine (6) To a mixture of 3-phenylxanthine (5,
500 mg, 2.19 mmol) and anhydrous K2CO3 (360 mg, 2.63 mmol) in di-
Anal. Calcd for C22H22N4O2: C, 70.57; H, 5.92; N, 14.96. Found: C, 70.50;
H, 6.04; N, 14.93.
1-Butyl-3-phenylxanthine (9) The mixture of 8 (620 mg, 0.166 mmol)
methylformamide (DMF, 10 ml) was added n-propyl bromide (900 mg, and 20% palladium hydroxide on carbon (600 mg) in MeOH (20 ml) was
5.26 mmol) at 0 °C; the reaction mixture was stirred overnight at room tem- shaken under hydrogen (3 atm) for 3 h. The catalyst was removed and the fil-
perature, then concentrated in vacuo. The residue was chromatogaraphed on trate concentrated in vacuo, and the residue crystallized to yield 9 (450 mg,
1
silica gel using CHCl3–MeOH (20 : 1) as an eluent to give 6 (404.5 mg, 95%). mp 204—205 °C (AcOEt–MeOH). H-NMR (CDCl3) d: 0.98 (3H, t,
1
68%). mp 224—225 °C (AcOEt–MeOH). H-NMR (CDCl3) d: 0.97 (3H, t,
Jϭ7.3 Hz), 1.25—1.90 (4H, m), 4.15 (2H, t, Jϭ7.3 Hz), 7.40—7.61 (5H,
Jϭ7.3 Hz), 1.95 (2H, sext., Jϭ7.3 Hz), 4.26 (2H, t, Jϭ7.3 Hz), 7.37—7.67 m), 7.65 (1H, s), 12.96 (1H, br s). IR (KBr) cmϪ1: 3438, 1748, 171, 1668.
(6H, m), 8.39 (1H, br s). IR (KBr) cmϪ1: 3272, 1712, 1696. Anal. Calcd for Anal. Calcd for C15H16N4O2: C, 63.37; H, 5.67; N, 19.71. Found: C, 61.99;
C14H14N4O2: C, 62.21; H, 5.22; N, 20.73. Found: C, 62.04; H, 5.21; N,
20.34.
H, 5.97; N, 18.41.
7-Acetonyl-3-phenylxanthine (2) The reaction with
9 (200 mg,
7-Benzyl-3-phenylxanthine (7) The reaction with 5 (1 g, 4.38 mmol), 0.704 mmol), K2CO3 (146 mg, 1.06 mmol) and bromo acetone (147 mg,
K2CO3 (0.72 g, 5.26 mmol) and benzyl bromide (0.9 g, 5.26 mmol) under the
1.06 mmol) under the same condition as the preparation of 6 gave 2
(163.2 mg, 68%). mp 167—168 °C (iso-propylether). H-NMR (CDCl3) d:
0.94 (3H, t, Jϭ7.3 Hz), 1.21—1.75 (4H, m), 2.36 (3H, s), 4.01 (2H, t,
1
same condition as the preparation of 6 gave 7 (1.03 g, 74%). mp 238—
1
239 °C. H-NMR (CDCl3) d: 5.49 (2H, s), 7.38—7.48 (10H, m), 7.52 (1H,
s), 8.09 (1H, br s). IR (KBr) cmϪ1: 1730, 1716, 1696. Anal. Calcd for Jϭ7.3 Hz), 5.17 (2H, s), 7.32—7.63 (6H, m). IR (KBr) cmϪ1: 1732, 1706,
Table 2. Physical Properties for Compounds 11 and 4
Analysis (%) Calcd (Found)
Compd. No.
Yield (%)
mp (°C)
Recryst. Solvent
Formula
C
H
N
11a
11b
11d
11e
4a
93
80
82
78
82
76
83
87
205—206
276—277
187—188
Ͼ290
AcOEt–MeOH
MeOH
C16H19N5O2
C13H13N5O2
C17H21N5O2
C14H15N5O2
C16H17N5O
C13H11N5O
C17H19N5O
C14H13N5O
61.33
(61.29)
57.56
(57.40)
62.37
(62.14)
58.94
(58.72)
65.07
(65.26)
61.65
(61.56)
66.00
(65.92)
62.91
6.11
(6.08)
4.83
(4.69)
6.47
(6.52)
5.30
(5.14)
5.80
(5.71)
4.38
(4.60)
6.19
(6.02)
4.90
22.35
(22.58)
25.82
(25.71)
21.39
(21.17)
24.55
(24.48)
23.71
(23.49)
27.65
(27.49)
22.64
(22.50)
26.20
AcOEt–MeOH
MeOH
204—205
Ͼ290
AcOEt–I.P.Ea)
AcOEt–MeOH
AcOEt–I.P.Ea)
AcOEt–MeOH
4b
4d
233—234
Ͼ290
4e
(62.77)
(4.88)
(26.29)
a) iso-propylether.
Table 3. Spectral Data for Compounds 11 and 4
Compd. No.
IR (KBr) cmϪ1
1H-NMR
11aa)
3415, 3282, 1635, 1610
0.95 (3H, t, Jϭ7.3 Hz), 1.85 (2H, sext., Jϭ7.3 Hz), 3.78 (4H, m), 4.35 (2H, t, Jϭ7.3 Hz), 7.29—7.56
(5H, m), 7.83 (1H, s)
3.58 (4H, m), 4.09 (1H, br s), 4.91 (1H, br s), 7.27—7.56 (6H, m), 7.78 (1H, s), 12.23 (1H, br s)
0.82 (3H, t, Jϭ7.3 Hz), 1.60—1.91 (4H, m), 3.49—3.56 (5H, m), 4.28 (2H, t, Jϭ7.3 Hz), 7.23—7.54
(5H, m), 7.84 (1H, s)
2.07 (2H, quint., Jϭ5.6 Hz), 3.40 (2H, t, Jϭ5.6 Hz), 3.87 (2H, t, Jϭ5.6 Hz), 7.37—7.55 (6H, m), 11.52
(1H, br s)
0.96 (3H, t, Jϭ7.3 Hz), 1.94 (2H, sext., Jϭ7.3 Hz), 4.05 (2H, t, Jϭ6.7 Hz), 4.07 (2H, t, Jϭ6.7 Hz), 4.23
(2H, t, Jϭ7.3 Hz), 7.38—7.46 (6H, m)
3.95—3.99 (4H, m), 7.41—7.57 (6H, m)
0.93 (3H, t, Jϭ7.3 Hz), 1.75—2.04 (4H, m), 3.57 (2H, t, Jϭ5.8 Hz), 3.93 (2H, t, Jϭ5.8 Hz), 4.28
(2H, t, Jϭ7.3 Hz), 7.37—7.59 (6H, m)
2.28 (2H, quint., Jϭ5.7 Hz), 3.73 (2H, t, Jϭ5.7 Hz), 4.18 (2H, t, Jϭ5.7 Hz), 6.87 (1H, br s), 7.29—7.80
(1H, s)
11ba)
11da)
3411, 3317, 3257, 1645, 1603
3313, 1631, 1606
11ea)
4ab)
3423, 1699, 1606
1674
4bb)
4db)
3444, 1697, 1685
1672, 1637
4eb)
3429, 1701, 1670
1H-NMR spectra were recorded in a) DMSO-d6 and b) CDCl3.