H.-C. Tong, K. R. Reddy, S.-T. Liu
FULL PAPER
3 H, CH3) ppm. 13C NMR (400 MHz, CDCl3): δ = 167.68, 150.64,
147.66, 145.10, 138.01, 135.90, 130.42, 128.98, 123.31, 113.54,
108.19, 52.35, 20.91 ppm. ESI-HRMS (TOF): calcd. for
7.02 (m, 2 H), 5.17 (br., 1 H, OH), 2.66 (t, J = 7.6 Hz, 2 H), 1.73
(m, 2 H), 1.43 (m, 2 H), 0.96 (t, J = 7.6 Hz, 3 H, CH3) ppm. 13C
NMR (400 MHz, CDCl3): δ = 156.07, 143.24, 142.41, 140.77,
137.97, 128.78, 128.68, 127.47, 127.12, 126.94, 118.72, 112.82,
C15H1079Br2NO5 [M
–
H]– 441.8926, found 441.8929.
C15H11Br2NO5 (445.06): calcd. C 40.48, H 2.49; found C 40.17, H 112.72, 35.22, 33.53, 22.32, 13.88 ppm. ESI-HRMS (TOF): calcd.
2.05.
for C22H21O [M – H]– 301.1592, found 301.1595. C22H22O (302.42):
calcd. C 87.38, H 7.33; found C 87.02, H 7.11.
4-Bromo-3-methylphenol (9a):[16] Yield 108.9 mg (97%). 1H NMR
Methyl 3,5-Dibromo-4-hydroxy-2-methyl-6-(p-nitrophenyl)benzoate
(3b):[14] Yield 117.2 mg (68%). 1H NMR (400 MHz, CDCl3): δ =
8.22 (d, J = 8.8 Hz, 2 H), 7.45 (d, J = 8.8 Hz, 2 H), 6.72 (d, J = (400 MHz, CDCl3): δ = 7.34 (d, J = 8.6 Hz, 1 H, Ar-H), 6.71 (d,
2.0 Hz, 1 H), 6.62 (d, J = 2.0 Hz, 1 H), 5.43 (br., 1 H, OH), 3.52
J = 2.9 Hz, 1 H, Ar-H), 6.54 (dd, J = 2.9, 8.6 Hz, 1 H, Ar-H), 5.13
(s, 3 H, OCH3), 2.35 (s, 3 H, CH3) ppm. 13C NMR (400 MHz,
(br., 1 H, OH), 2.31 (s, 3 H, CH3) ppm. 13C NMR (400 MHz,
CDCl3): δ = 169.36, 156.33, 147.61, 147.12, 140.46, 139.16, 128.85, CDCl3): δ = 154.47, 139.13, 132.99, 117.75, 115.46, 114.44,
127.57, 123.42, 117.14, 113.99, 51.81, 20.03 ppm. ESI-HRMS 22.87 ppm. ESI-HRMS (TOF): calcd. for C7H679BrO [M – H]–
(TOF): calcd. for C15H12NO5 [M – H]– 286.0715, found 286.0713.
184.9608; found 184.9603.
4-Bromo-5-isopropyl-2-methylphenol (10a):[17] Yield 133.3 mg
(97%). H NMR (400 MHz, CDCl3): δ = 7.26 (s, 1 H, Ar-H), 6.68
Methyl
3,5-Dibromo-4-hydroxy-6-(p-methoxyphenyl)-2-methyl-
1
benzoate (4a): Yield 242.6 mg (94%), yellow solid, m.p. 126–127 °C.
1H NMR (400 MHz, CDCl3): δ = 7.12 (d, J = 8.8 Hz, 2 H), 6.89
(d, J = 8.8 Hz, 2 H), 3.83 (br., 1 H, OH), 3.80 (s, 3 H, OCH3), 3.44
(s, 3 H, OCH3), 2.35 (s, 3 H, CH3) ppm. 13C NMR (400 MHz,
CDCl3): δ = 168.36, 159.26, 150.13, 139.70, 134.85, 130.63, 130.25,
129.24, 113.32, 111.95, 109.68, 55.13, 52.08, 20.63 ppm. ESI-
HRMS (TOF): calcd. for C16H1379Br2O4 [M – H]– 426.9181, found
426.9184. C16H14Br2O4 (430.09): calcd. C 44.68, H 3.28; found C
44.45, H 2.97.
(s, 1 H, Ar-H), 4.89 (br., 1 H, OH), 3.30 (m, J = 6.9 Hz, 1 H, CH),
2.17 (s, 3 H, CH3), 1.18 (d, J = 6.9 Hz, 6 H, CH3) ppm. 13C NMR
(400 MHz, CDCl3): δ = 153.18, 146.01, 134.33, 123.23, 114.19,
113.16, 32.49, 22.72, 15.01 ppm. ESI-HRMS (TOF): calcd. for
C10H1279BrO [M – H]– 227.0077, found 227.0074.
2,4,6-Tribromobenzene-1,3-diol (11a):[18] Yield 181 mg (87%). 1H
NMR (400 MHz, CDCl3): δ = 7.57 (s, 1 H, ArH), 5.89 (s, 2 H, OH)
ppm. 13C NMR (400 MHz, CDCl3): δ = 149.70, 132.90, 100.29,
98.20 ppm. ESI-HRMS (TOF): calcd. for C6H279Br3O [M – H]–
326.7661, found 326.7656.
Methyl 3,5-Dibromo-6-(p-chlorophenyl)-4-hydroxy-2-methylbenzo-
ate (5a): Yield 258.1 mg (97%), m.p. 130–131 °C. 1H NMR
(400 MHz, CDCl3): δ = 7.35 (d, J = 8.4 Hz, 2 H), 7.14 (d, J =
8.4 Hz, 2 H), 3.94 (br., 1 H, OH), 3.44 (s, 3 H, OCH3), 2.35 (s, 3
H, CH3) ppm. 13C NMR (400 MHz, CDCl3): δ = 168.02, 150.31,
138.79, 136.74, 135.24, 134.25, 130.47, 128.82, 128.24, 112.60,
108.97, 52.17, 20.71 ppm. ESI-HRMS (TOF): calcd. for
1
2-Bromobenzene-1,4-diol (13a):[19] Yield 99.8 mg (88%). H NMR
(400 MHz, [D6]acetone): δ = 6.65 (dd, J = 8, 3 Hz, 1 H), 6.80 (d,
J = 8 Hz, 1 H), 6. 90 (d, J = 3 Hz, 1 H), 8.5 (br., 2 H, OH) ppm.
13C NMR (400 MHz, CDCl3): δ = 151.28, 147.11, 119.2, 117.33,
116.3, 110.5 ppm.
2,4,6-Tribromophenol (14a):[20] Yield 176.6 mg (89%). 1H NMR
(400 MHz, CDCl3): δ = 7.56 (s, 2 H) ppm. 13C NMR (400 MHz,
CDCl3): δ = 148.87, 134.14, 112.59, 110.32 ppm. ESI-HRMS
(TOF): calcd. for C6H379Br3O [M – H]– 327.7734, found 327.7729.
C15H1079Br235ClO3 [M
C15H11Br2ClO3 (434.51): calcd. C 41.46, H 2.55; found C 41.09, H
2.22.
–
H]–, 430.8685, found 430.8686.
Methyl 3,5-Dibromo-4-hydroxy-2,6-dimethylbenzoate (6a): Yield
188.6 mg (93%), white solid, m.p. 140–141 °C: 1H NMR
(400 MHz, CDCl3): δ = 6.20 (br., 1 H, OH), 3.92 (s, 3 H, OCH3),
2.33 (s, 6 H, CH3) ppm. 13C NMR (400 MHz, CDCl3): δ = 169.18,
150.01, 134.55, 128.66, 110.41, 52.51, 20.72 ppm. ESI-HRMS
Gram-Scale Preparation of 10a: A mixture of 10 (1.0 g, 6.67 mmol),
Cu(OAc)2 (48 mg, 0.26 mmol) and LiBr (1.74 g, 20 mmol) in a
solution of CF3COOH (2 g) and CH3CN (4 g) was heated at 80 °C
under O2 (1 atm) overnight, The reaction mixture was poured into
a saturated NaCl solution (10 mL), extracted with CH2Cl2 (2ϫ
20 mL) and dried with MgSO4. After removal of the solvents, the
residue was passed through a short silica gel column. Compound
10a was obtained upon concentration (0.98 g, 97%).
(TOF): calcd. for C10H979Br2O3 [M
334.8922. C10H10Br2O3 (338.00): calcd. C 35.54, H 2.98; found C
35.35, H 2.78.
Methyl 4-Hydroxy-2,6-dimethylbenzoate (6b):[15] Yield 75.7 mg
(70%). H NMR (400 MHz, CDCl3): δ = 6.45 (s, 2 H, ArH), 5.37
–
H]– 334.8918, found
1
Supporting Information (see footnote on the first page of this arti-
cle): NMR spectra of the obtained compounds.
(br., 1 H, OH), 3.84 (s, 3 H, OCH3), 2.24 (s, 6 H, CH3) ppm. 13C
NMR (400 MHz, CDCl3): δ = 170.41, 156.23, 137.92, 125.99,
114.76, 114.47, 51.69, 20.06 ppm. ESI-HRMS (TOF): calcd. for
C10H11O3 [M – H]– 179.0708, found 179.0708.
Acknowledgments
Methyl 4-Hydroxy-2-methyl-6-(thiophen-2-yl)benzoate (7b): Yield
117.7 mg (79%), white solid, m.p. 113–114 °C. 1H NMR
(400 MHz, CDCl3): δ = 7.25–7.23 (m, 1 H), 6.97–6.96 (m, 2 H),
6.71 (d, J = 2.4 Hz, 1 H), 6.57 (d, J = 2.4 Hz, 1 H), 6.17 (br., 1 H,
OH), 3.67 (s, 3 H, OCH3), 2.25 (s, 3 H, CH3) ppm. 13C NMR
(400 MHz, CDCl3): δ = 170.94, 156.30, 141.64, 137.79, 134.12,
127.31, 125.79, 125.76, 125.54, 116.48, 114.38, 52.22, 19.67 ppm.
ESI-HRMS (TOF): calcd. for C13H11O3S [M – H]– 247.0429, found
247.0428. C13H12O3S (248.30): calcd. C 62.88, H 4.87; found C
62.56, H 4.59.
We thank the National Science Council for financial support
(NSC-100-2113-M002-001-MY3).
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[3] Recent reviews: a) S. E. Allen, R. R. Walvoord, R. Padilla-Sali-
nas, M. C. Kozlowski, Chem. Rev. 2013, 113, 6234–6458; b)
K. M. Engle, J.-Q. Yu, J. Org. Chem. 2013, 78, 8927–8955; c)
A. J. Hickman, M. S. Sanford, Nature 2012, 484, 177–185; d)
C. Zhang, C. Tang, N. Jiao, Chem. Soc. Rev. 2012, 41, 3464–
3-(p-Butylphenyl)-5-phenylphenol (8b): Yield 108.9 mg (60%). 1H
NMR (400 MHz, CDCl3): δ = 7.60 (d, J = 6.8 Hz, 2 H), 7.52 (d,
J = 8.4 Hz, 2 H), 7.44–7.34 (m, 4 H), 7.25 (d, J = 8.4 Hz, 2 H),
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