The Journal of Organic Chemistry
Article
(phenylsulfonylmethyl)benzene (3.70 g, 80%) in a pure form. White
powder; mp 66−67 °C; H NMR (500 MHz, CDCl3) δ 0.89−0.91
32.5, 55.0, 57.4, 74.7, 76.5, 116.9, 122.7, 123.1, 126.5, 127.0, 128.1,
128.6, 128.7, 129.6, 129.7, 133.7, 138.3, 151.4, 151.7; HRMS
(MALDI-TOF) 456.1988 (M+), calcd for C26H32O5S 456.1970.
(iv). Synthesis of 1d. The synthesis of 1d was carried out according
to the procedure described above for 1c. Purification: chromatography
(EtOAc/hexane, 1:3). Yield: 2.62 g, 96%. White powder; mp 94−95
1
(m, 6H), 1.33−1.45 (m, 12H), 1.69−1.73 (m, 2H), 1.78−1.83 (m,
2H), 3.15 (s, br, 1H), 3.65 (t, J = 6.7 Hz, 2H), 3.98 (t, J = 6.5 Hz, 2H),
4.43 (s, 2H), 4.51 (s, 2H), 6.27 (s, 1H), 6.91 (s, 1H), 7.49 (t, J = 7.7
Hz, 2H), 7.63 (t, J = 7.0 Hz, 1H), 7.71 (d, J = 7.7 Hz, 2H); 13C{1H}
NMR (125 MHz, CDCl3) δ 14.1, 22.6, 25.60, 25.64, 29.0, 29.1, 31.5,
31.6, 59.5, 62.7, 68.98, 69.04, 115.0, 116.9, 117.6, 128.8, 129.1, 133.88,
133.94, 137.9, 148.1, 149.6; HRMS (MALDI-TOF) 485.2357 (M +
Na+), calcd for C26H38O5SNa 485.2338.
1
°C; H NMR (500 MHz, CDCl3) δ 1.00−1.05 (m, 6H), 1.50−1.64
(m, 4H), 1.80−1.86 (m, 2H), 1.90−1.96 (m, 2H), 3.98 (t, J = 6.4 Hz,
2H), 4.09 (t, J = 6.7 Hz, 2H), 5.30 (s, 2H), 7.45 (t, J = 8.0 Hz, 2H),
7.58−7.68 (m, 3H), 7.75 (d, J = 7.3 Hz, 2H), 7.98 (d, J = 8.0 Hz, 1H),
8.21 (d, J = 7.9 Hz, 1H), 10.51 (s, 1H); 13C{1H} NMR (125 MHz,
CDCl3) δ 13.9, 14.0, 19.3, 32.2, 32.3, 52.3, 75.6, 78.8, 114,9, 123.4,
123.5, 124.6, 127.8, 128.5, 128.7, 129.2, 129.4, 131.4, 133.4, 139.5,
152.5, 159.1, 192.1; HRMS (MALDI-TOF) 454.1812 (M+), calcd for
C26H30O5S 454.1814.
(iv). Synthesis of 1c. A flask was charged with 1,2-bis(hexyloxy)-4-
hydroxymethyl-5-(phenylsulfonylmethyl)benzene (2.78 g, 6.0 mmol),
MnO2 (5.22 g, 60.0 mmol), and CH2Cl2 (20.0 mL). After the resulting
mixture had been heated at 50 °C overnight, it was cooled to room
temperature and filtered. The filtrate was dried in vacuo, and the
residue was subjected to chromatography (EtOAc/hexane, 1:3) to give
Synthesis of 1e. (i). Synthesis of 2-Cyano-4-fluoro-1-
(phenylsulfonylmethyl)benzene. The synthesis of 2-cyano-4-fluoro-
1-(phenylsulfonylmethyl)benzene was carried out according to the
procedure described above for 1-cyano-2-(phenylsulfonylmethyl)-
benzene. Purification: recrystallization from CH2Cl2/hexane. Yield:
1
1c (2.52 g, 91%) in a pure form. White powder; mp 96−97 °C; H
NMR (500 MHz, CDCl3) δ 0.90−0.94 (m, 6H), 1.34−1.37 (m, 8H),
1.47−1.49 (m, 4H), 1.81−1.87 (m, 4H), 4.00 (t, J = 6.7 Hz, 2H), 4.04
(t, J = 6.4 Hz, 2H), 4.90 (s, 2H), 6.79 (s, 1H), 7.20 (s, 1H), 7.45 (t, J =
7.7 Hz, 2H), 7.60 (t, J = 7.3 Hz, 1H), 7.67 (d, J = 7.3 Hz, 2H), 9.67 (s,
1H); 13C{1H} NMR (125 MHz, CDCl3) δ 14.0, 22.5, 25.5, 25.6, 28.8,
28.9, 31.4, 31.5, 57.2, 69.18, 69.21, 116.1 (d), 116.6 (d), 123.2, 127.5,
128.7, 128.8, 133.8, 137.8, 149.1, 153.1, 189.7; HRMS (MALDI-TOF)
460.2289 (M+), calcd for C26H36O5S 460.2283.
1
1.87 g, 68%. Pale-yellow powder; mp 157−159 °C; H NMR (500
MHz, CDCl3) δ 4.55 (s, 2H), 7.27 (dd, J = 2.8 Hz, J = 8.0 Hz, 1H),
7.35 (dt, J = 2.8 Hz, J = 8.0 Hz, 1H), 7.53 (t, J = 7.6 Hz, 2H), 7.58−
7.61 (m, 1H), 7.67−7.73 (m, 3H); 19F NMR (282 MHz, CDCl3) δ
−91.42 (s, 1F); 13C{1H} NMR (125 MHz, CDCl3) δ 59.5 (t), 115.4
(d), 115.6 (d, JC−F = 9.3 Hz), 119.5 (dd, J = 5.9 Hz, JC−F = 25.1 Hz),
120.6 (dd, J = 3.3 Hz, JC−F = 21.4 Hz), 127.7 (d, JC−F = 4.2 Hz), 128.5,
129.3, 134.2 (d, JC−F = 7.7 Hz), 134.3, 137.1, 161.9 (d, JC−F = 252.7
Hz); HRMS (MALDI-TOF) 298.0343 (M + Na+), calcd for
C14H10FNNaO2S 298.0314.
Synthesis of 1d. (i). Synthesis of 1,4-Dibutoxy-2-methylnaph-
thalene. A flask was charged with 1,4-diacetoxy-2-methylnaphthalene
(2.58 g, 10.0 mmol), NaH (1.06 mg, 44.0 mmol), BuI (7.36 g, 40.0
mmol), HMPA (7.88 g, 44.0 mmol), and THF (30.0 mL) under N2.
After the resulting mixture had been heated at 80 °C for 48 h, it was
cooled to room temperature. After the usual workup with CH2Cl2/
H2O, the solvents were evaporated in vacuo, and the residue was
subjected to chromatography (CH2Cl2/hexane, 1:3) to give 1,4-
dibutoxy-2-methylnaphthalene (2.64 g, 92%) in a pure form. White
(ii). Synthesis of 1e. The synthesis of 1e was carried out according
to the procedure described above for 1a. Purification: chromatography
(EtOAc/CH2Cl2/hexane, 1:2:4). Yield: 723.6 mg, 52%. White powder;
mp 138−140 °C; 1H NMR (300 MHz, CDCl3) δ 4.94 (s, 2H), 7.23−
7.30 (m, 1H), 7.34−7.39 (m, 1H), 7.44−7.50 (m, 3H), 7.60−7.69 (m,
3H), 9.84 (s, 1H); 19F NMR (282 MHz, CDCl3) δ −94.03 (s, 1F);
13C{1H} NMR (75 MHz, CDCl3) δ 56.9 (t), 119.6 (d, JC−F = 22.3
Hz), 120.6 (d, JC−F = 21.4 Hz), 124.7 (d, JC−F = 3.4 Hz), 128.4, 128.9,
134.0, 135.6 (d, JC−F = 7.8 Hz), 136.4 (d, J = 1.2 Hz, JC−F = 5.9 Hz),
137.7, 162.9 (d, JC−F = 251.7 Hz), 190.0 (d); HRMS (MALDI-TOF)
301.0331 (M + Na+), calcd for C14H11FO3SNa 301.0311.
1
powder; mp 36−37 °C; H NMR (500 MHz, CDCl3) δ 1.00−1.04
(m, 6H), 1.56−1.65 (m, 4H), 1.85−1.91 (m, 4H), 2.42 (s, 3H), 3.88
(t, J = 6.7 Hz, 1H), 4.06 (t, J = 6.5 Hz, 1H), 6.58 (s, 1H), 7.39 (t, J =
7.1 Hz, 1H), 7.48 (t, J = 7.0 Hz, 1H), 8.05 (d, J = 8.3 Hz, 1H), 8.22 (d,
J = 8.6 Hz, 1H); 13C{1H} NMR (125 MHz, CDCl3) δ 13.9, 14.1, 16.4,
16.5, 19.5, 31.4, 32.6, 67.9, 73.6, 107.5 (d), 121.5, 122.2, 124.3, 125.3,
125.7, 126.2, 128.9, 145.8, 150.8; HRMS (MALDI-TOF) 286.1935
(M+), calcd for C19H26O2 286.1933.
Synthesis of 1f. (i). Synthesis of Methyl 4-Bromo-2-methyl-
benzoate.27 To a suspension of 4-bromo-2-methylbenzoic acid (10.75
g, 50.0 mmol) and MeOH (60.0 mL) was added dropwise SOCl2
(11.90 g, 100.0 mmol) during the course of 10−15 min at 0 °C, and
the resulting mixture was heated at refluxing temperature overnight
and then cooled to room temperature. After the usual workup with
CH2Cl2/H2O and brine, evaporation of the solvents in vacuo afforded
methyl 4-bromo-2-methylbenzoate (11.45 g, 100%) in a pure form.
( i i ) . S y n t h e s i s o f 1 , 4 - D i b u t o x y - 2 - m e t h y l - 3 -
(phenylsulfonylmethyl)naphthalene. The synthesis of 1,4-dibutoxy-
2-methyl-3-(phenylsulfonylmethyl)naphthalene was carried out ac-
cording to the procedure described above for 6. Purification:
chromatography (EtOAc/hexane, 1:8). Yield: 11.2 g, 85%. White
powder; mp 51−53 °C; 1H NMR (500 MHz, CDCl3) δ 0.97 (t, J = 7.3
Hz, 3H), 1.04 (t, J = 7.6 Hz, 3H), 1.40−1.45 (m, 2H), 1.60−1.69 (m,
4H), 1.88−1.94 (m, 2H), 2.49 (s, 3H), 3.74 (t, J = 6.4 Hz, 2H), 3.90
(t, J = 6.8 Hz, 2H), 7.34−7.41 (m, 3H), 7.49 (dd, J = 1.3 Hz, J = 8.3
Hz, 1H), 7.55 (t, J = 7.4 Hz, 1H), 7.63 (d, J = 8.3 Hz, 2H), 7.74 (d, J =
8.3 Hz, 1H), 8.05 (d, J = 8.6 Hz, 1H); 13C{1H} NMR (125 MHz,
CDCl3) δ 13.38, 13.42, 13.9, 14.0, 19.2, 19.4, 32.4 (d), 55.6, 73.9, 74.6,
118.0, 122.4, 122.6, 125.4, 126.7, 127.2, 128.5, 129.4, 133.4, 138.9,
149.4, 151.4; HRMS (MALDI-TOF) 440.2032 (M+), calcd for
C26H32O4S 440.2021.
(iii). Synthesis of 1,4-Dibutoxy-2-hydroxymethyl-3-
(phenylsulfonylmethyl)naphthalene. The synthesis of 1,4-dibutoxy-
2-hydroxymethyl-3-(phenylsulfonylmethyl)naphthalene was carried
out according to the procedure described above for 1,2-bis-
(hexyloxy)-4-hydroxymethyl-5-(phenylsulfonylmethyl)benzene. Purifi-
cation: chromatography (EtOAc/hexane, 1:3). Yield: 2.19 g, 80%.
Colorless oil; 1H NMR (500 MHz, CDCl3) δ 0.97 (t, J = 7.4 Hz, 3H),
1.06 (t, J = 7.6 Hz, 3H), 1.39−1.46 (m, 2H), 1.61−1.69 (m, 4H),
1.94−2.00 (m, 2H), 3.36 (s, 1H), 3.74 (t, J = 6.1 Hz, 2H), 4.14 (t, J =
6.4 Hz, 2H), 4.82 (s, 2H), 5.01 (s, 2H), 7.40 (t, J = 7.6 Hz, 2H), 7.46
(t, J = 7.1 Hz, 1H), 7.53 (t, J = 7.0 Hz, 1H), 7.59 (t, J = 7.4 Hz, 1H),
7.67 (d, J = 8.2 Hz, 2H), 7.75 (d, J = 8.6 Hz, 1H), 8.11 (t, J = 8.6 Hz,
1H); 13C{1H} NMR (125 MHz, CDCl3) δ 13.9, 14.1, 19.2, 19.4, 32.3,
1
Colorless oil; H NMR (500 MHz, CDCl3) δ 2.57 (s, 3H), 3.88 (s,
3H), 7.36 (d, J = 8.5 Hz, 1H), 7.40 (s, 1H), 7.77 (d, J = 8.6 Hz, 1H);
13C{1H} NMR (75 MHz, CDCl3) δ 21.5 (d), 51.9 (d), 126.6, 128.2,
128.8 (d), 132.1, 134.4 (d), 142.4, 167.1.
(ii). Synthesis of Methyl 4-Bromo-2-(phenylsulfonylmethyl)-
benzoate. A 100 mL flask was charged with methyl 4-bromo-2-
methylbenzoate (4.58 g, 20.0 mmol), NBS (3.74 g, 21.0 mmol), BPO
(484.0 mg, 2.0 mmol), and CCl4 (50.0 mL). After the mixture had
been stirred at 80 °C for 10 min and at 90 °C overnight, it was allowed
to cool to room temperature and filtered. The filtrate was washed with
NaHCO3(aq), dried over MgSO4, and filtered. The solvents were
evaporated in vacuo. To the crude product were added benzenesulfinic
acid sodium salt dihydrate (4.80 g, 24.0 mmol) and DMF (40.0 mL).
After the mixture had been stirred at 80 °C overnight, it was cooled to
room temperature. After the usual workup with water and EtOAc, the
solvents were evaporated in vacuo, and the residue was subjected to
recrystallization from CH2Cl2/hexane to give methyl 4-bromo-2-
(phenylsulfonylmethyl)benzoate (5.24 g, 71%). Pale-yellow powder;
mp 105−107 °C; 1H NMR (500 MHz, CDCl3) δ 3.75 (s, 3H), 5.02 (s,
2H), 7.44 (d, J = 1.9 Hz, 1H), 7.48 (t, J = 7.7 Hz, 2H), 7.55 (dd, J =
1.9 Hz, J = 8.3 Hz, 1H), 7.63 (t, J = 7.3 Hz, 1H), 7.66 (d, J = 7.0 Hz,
11601
dx.doi.org/10.1021/jo502248p | J. Org. Chem. 2014, 79, 11592−11608