240 JOURNAL OF CHEMICAL RESEARCH 2012
Scheme 3
in water (20 mL). After the mixture was stirred at reflux for 5 h it was
cooled and neutralised with a solution of HCl (1%). Then, the mixture
was extracted with EtOAc and washed twice with water. After drying
over Na2SO4, the solvent was removed under reduced pressure. The
natural bromophenol 1 was the sole product obtained as a pale orange
was hydrolysed by reflux with 0.16M NaOH solution (in diox-
ane–water:1:1 V/V) and was converted (97%) into the natural
bromophenol 1 as the sole product to prove this method’s
effectiveness (Scheme 3).
1
solid (0.164 g, 97%), m.p. 202–205 °C (lit.,24 199.0–199.8 °C). H
Conclusion
NMR (200 MHz, CD3COCD3): δ 8.95 (s, OH, 2H); 8.34 (s, OH, 2H);
6.57 (s, 2H); 4.05 (s, CH2, 2H).25,26
This report includes a concise strategy for the direct synthesis
of acetylated phenols from aryl-methyl ethers. The procedure
combines the BBr3 demethylation of ethers with acetylation of
OH groups. After BBr3 demethylation, acetylated compounds
were produced by the addition of acetic acid instead of water,
methanol or another additional reagent. Thus, an efficient
method was developed to achieve easier purification of natural
phenolic compounds, useful in synthesis, by the functional
group changing, from OMe to OAc in organic solvents under
mild conditions and in a single step.
The author is indebted to Artvin Çoruh University for financial
support of this work.
Electronic Supplementary Information
Found and literature data on melting points and NMR spectra
of the known products together with observed spectra for 20
and 30 have been deposited in the ESI available through stl.
publisher.ingentaconnect.com/content/stl/jcr/supp-data.
Experimental
Received 12 October 2011; accepted 23 February 2012
Paper 1100927 doi: 10.3184/174751912X13324176277811
Published online: 17 April 2012
All chemicals and solvents were commercially available. Column
chromatography was performed on silica gel (SiO2, 60 mesh; Merck).
TLC was performed on E. Merck Silica Gel 60 F254 plate (0.2 mm).
Melting points were determined on a Buchi 530 capillary melting
apparatus and were uncorrected. IR Spectra were obtained from solu-
tions in 0.1-mm cells on Perkin Elmer Spectrum One FT-IR spectrom-
References
1
2
3
4
J.F.W. McOmie and M.L. Watts, Chem. Ind. Lond., 1963, 1658.
J.F.W. McOmie, M.L. Watts and D.E. West, Tetrahedron., 1968, 24, 2289.
R.L. Burwell, Chem. Rev. 1954, 54, 615.
H.S. Lee, T.H. Lee, J.H. Lee, C.S. Chae, S.C. Chung, D.S. Shin, J. Shin and
K.B. Oh, J. Agric. Food Chem., 2007, 55, 6923.
1
eter. H and 13C NMR spectra were recorded on 400 (100)-MHz
Bruker Avance III and Varian Mercury spectrometers and are reported
in δ units with Me4Si as internal standard. Elemental analyses were
carried out on a Leco CHNS-932 analyser (see Electronic Supplemen-
tary Information).
5
6
7
8
9
D.Y. Shi, F. Xu, J. He, L. Jing, J. Li, X. Fan and L.J. Han, Chin. Sci. Bull.,
2008, 53, 2476.
X. Xu, F. Song, S. Wang, S. Li, F. Xiao, J. Zhao, Y. Yang, S. Shang, L. Yang
and J. Shi, J. Nat. Prod., 2004, 67, 1661.
K. Kurata, K. Taniguchii, K. Takashima, I. Hayashi and M. Suzuki,
Phytochemistry., 1997, 45, 485.
K.B. Oh, J.H. Lee, S.C. Chung, J. Shin, H.J. Shin, H.K. Kim and H.S. Lee,
Bioorg. Med. Chem. Lett., 2008, 18, 104.
Acetylation of aryl methyl ethers: general procedure
A solution of bis(3,4-dimethoxyphenyl)methanone (12, 1.00 g, 3.31 mmol)
in CH2Cl2 (30 mL) was cooled to 0 °C and then a solution of BBr3
(2.1 mL, 21.8 mmol) in CH2Cl2 (22.3 mL) was added dropwise under
N2 over 5 minutes. After the cold bath was removed, the mixture was
stirred at RT and under N2 for 1 day. After one day mixing and moni-
toring with TLC, the mixture was cooled to 0 °C and glacial acetic
acid (3.65 g) was added drop by drop over 5 min. After stirring for an
additional 1 h, the mixture was extracted with a cooled Na2CO3 aque-
ous solution (5%) and washed with 0–5 °C water. Then the organic
phase was dried over Na2SO4 and solvent was evaporated. bis(3,4-dia
cetoxyphenyl)methanone (20) was obtained as a white solid (1.23 g,
90%).
Bis(3,4-diacetoxyphenyl)methanone (20): M.p. 192–193 °C. Found:
C, 60.49; H, 4.25. C21H18O9 requires: C, 60.87; H, 4.38%; IR (KBr)
2398, 2073, 1777, 1729, 1663, 1606, 1585, 1501, 1463, 1421, 1372,
1294, 1262, 1200 cm−1; δH (400 MHz, CDCl3) 7.71 (dd, 2H, A part of
AB - system, J = 1.8, 8.4 Hz, aromatic), 7.66 (s, 2H, aromatic), 7.32
(dd, 2H, B part of AB - system, J = 0.7, 8.4 Hz, aromatic), 2.30 (s, 6H,
CH3), 2.29 (s, 6H, CH3); δC (100 MHz, CDCl3) 192.5 (CO), 168.2
(CO, acetate), 168.0 (CO, acetate), 146.0 (C), 142.3 (C), 135.5 (C),
128.7 (C), 125.7 (CH), 123.8 (CH), 20.9 (CH3), 20.8 (CH3).
5,5′-Methylenebis(1,2-diacetoxy-3,4-dibromobenzene) (30): (Crys-
tallised from CH2Cl2/hexane ratio of 2/1 and the product was obtained
as yellow crystals.) M.p. 213–215 °C. Found: C, 34.86; H, 2.26.
C21H16Br4O8 requires: C, 35.23; H, 2.25%; IR (KBr) 1781, 1725, 1634,
1586, 1448, 1429, 1371, 1276, 1199, 1140 cm−1; δH (400 MHz, CDCl3)
6.85 (s, 2H, aromatic), 4.30 (s, 2H, CH2), 2.35 (s, 6H, CH3), 2.26 (s,
6H, CH3); δC (100 MHz, CDCl3) 167.9 (CO, acetate), 167.2 (CO,
acetate), 142.8 (C), 140.9 (C), 138.1 (C), 125.1 (C), 124.1 (CH), 122.6
(C), 45.4 (CH2) 20.8 (CH3), 20.6 (CH3).
N. Xu, X. Fan, X.Yan, X. Li, R. Niu and C.K. Tseng, Phytochemistry, 2003,
62, 1221.
10 H.T. Balaydin, I. Gulcin, A. Menzek, S. Goksu and E. Sahin, J. Enzyme
Inhib. Med. Chem., 2010, 25, 685.
11 X.J. Duan, X.M. Li and B.G. Wang, J. Nat. Prod., 2007, 70, 1210.
12 W. Wang, Y. Okada, H. Shi, Y. Wang and T. Okuyama, J. Nat. Prod., 2005,
68, 620.
13 H.T. Balaydin, H. Soyut, D. Ekinci, S. Goksu, S. Beydemir, A. Menzek and
E. Sahin, J. Enzym. Inhib. Med. Ch., 2012, 27, 43.
14 H.T. Balaydin, Y. Akbaba, A. Menzek, E. Sahin and S. Goksu, Arkivoc.,
2009, XIV, 75.
15 H.T. Balaydin, S. Durdagi, D. Ekinci, M. Senturk, S. Goksu andA. Menzek,
J. Enzym. Inhib. Med. Ch., 2011, doi: 10.3109/14756366.2011.596836.
16 H.T. Balaydin, M. Senturk and A. Menzek, Bioorg. Med. Chem. Lett.,
2012, 22, 1352.
17 Y. Akbaba, H.T. Balaydin, S. Goksu, E. Sahin and A. Menzek, Helv. Chim.
Acta., 2010, 93, 1127.
18 M. Harig, B. Neumann, H.G. Stammler and D. Kuck, Eur. J. Org. Chem.,
2004, 11, 2381.
19 S. Farhadi and S. Panahandehjoo, Eur. J. Chem., 2010, 1, 335.
20 A.K. Chakraborti, J. Org. Chem., 2006, 71, 5785.
21 Y. Aoki, N. Hirai, S. Sakaguchi and Y. Ishii, Tetrahedron., 2005, 61,
10995.
22 W. Bencze, Helv. Chim. Acta, 1956, 39, 923.
23 C. Huang, N. Ghavtadze, B. Chattopadhyay and V. Gevorgyan, J. Am.
Chem. Soc., 2011, 133, 17630.
24 J.Li, S.J. Guo, H. Su, L.J. Han and D.Y. Shi., Chin. Chem. Lett., 2008, 19,
1290.
25 H.T. Balaydin, I. Gulcin, A. Menzek, S. Goksu and E. Sahin, J. Enzyme
Inhib. Med. Chem., 2010, 25, 685.
26 K. Kurata and T. Amiya, Chem. Lett., 1977, 6, 1435.
Hydrolysis of 30: To a solution of 30 (0.220 g, 0.31 mmol) in
dioxane (20 mL) was added a solution of NaOH (0.25 g, 6.25 mmol)