230 JOURNAL OF CHEMICAL RESEARCH 2009
Jꢀ ꢀꢁꢉꢎꢀ+]ꢈꢊꢀꢎꢉꢎꢋ±ꢎꢉꢎꢁꢀꢅPꢊꢀꢎ+ꢈꢊꢀꢎꢉꢎꢂꢀꢅGꢊꢀꢆ+ꢊ Jꢀ ꢀꢁꢉꢎꢀ+]ꢈꢊꢀꢎꢉꢋꢏ±ꢎꢉꢋꢂꢀ
ꢅVHULHVꢀ RIꢀ Pꢊꢀ ꢁ+ꢈꢊꢀ ꢎꢉꢐꢂ±ꢎꢉꢇꢆꢀ ꢅVHULHVꢀ RIꢀ Pꢊꢀ ꢋ+ꢈꢊꢀ ꢋꢉꢍꢏꢀ ꢅVH[WHWꢊꢀ ꢎ+ꢊ
J=7.1Hz),5.13(s,1H),6.76(d,2H,J =8.5Hz),7.03(d,2H,J =8.5Hz).
13C NMR G: 14.1, 22.5, 22.7, 27.7, 29.4, 31.8, 38.6, 39.1, 115.1,
128.0, 140.3, 153.4. Anal. Calcd for C14H22O·C7H5NO: C, 77.50; H,
8.36; N, 4.30. Found: C, 77.67; H, 8.59; N, 4.19%.
4-(3'-Octyl)phenolꢑꢀ %ꢉSꢉꢀ ꢎꢋꢎ±ꢎꢋꢋꢀ&ꢒꢏꢉꢁꢇꢀ PP+Jꢓꢀ PꢉSꢉꢀ ꢎꢎꢐꢉꢇ±
115°C (phenylcarbamate); IR (neat): 3337 cm-1; 1H NMR G: 0.74 (t,
3H, J = 7.4 Hz), 0.83 (t, 3H, Jꢀ ꢀꢁꢉꢏꢀ+]ꢈꢊꢀꢎꢉꢏꢁ±ꢎꢉꢎꢁꢀꢅVHULHVꢀRIꢀPꢊꢀꢋ+ꢈꢊꢀ
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(series of m, 2H), 2.32 (tt, 1H, J = 9.6, 4.8 Hz), 5.12 (s, 1H), 6.76 (d,
2H, J = 8.5 Hz), 6.99 (d, 2H, J = 8.5 Hz); 13C NMR Gꢀ 12.2, 14.1,
22.6, 27.3, 29.9, 32.0, 36.7, 47.0, 115.0, 128.7, 138.4, 153.3. Anal.
Calcd for C14H22O·C7H5NO: C, 77.50; H, 8.36; N, 4.30. Found: C,
77.33; H, 8.57; N, 4.20%.
4-(2'-Methyl-2'-octyl)phenolꢑꢀ %ꢉSꢉꢀ ꢎꢋꢃ±ꢎꢋꢂꢀ&ꢒꢏꢉꢁꢀ PP+Jꢓꢀ PꢉSꢉꢀ
ꢂꢂꢉꢇ±ꢎꢏꢏꢀ&ꢀ ꢅSKHQ\OFDUEDPDWHꢈꢓꢀ ,5ꢀ ꢅQHDWꢈꢑꢀ ꢆꢆꢆꢁꢀ FP-1; 1H NMR
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ꢅVHULHVꢀRIꢀPꢊꢀꢐ+ꢈꢊꢀꢎꢉꢎꢂ±ꢎꢉꢋꢆꢀꢅVHULHVꢀRIꢀPꢊꢀꢋ+ꢈꢊꢀꢎꢉꢋꢇꢀꢅVꢊꢀꢍ+ꢈꢊꢀꢎꢉꢇꢆ±
1.55 (series of m, 2H), 4.68 (s, 1H), 6.76 (d, 2H, J = 8.6 Hz), 7.18 (d,
2H, J = 8.6 Hz); 13C NMR Gꢀ 14.1, 22.7, 24.7, 29.1, 30.0, 31.8, 37.1,
44.8, 114.7, 127.0, 142.2, 153.0. Anal. Calcd for C15H24O·C7H5NO:
C, 77.84; H, 8.61; N, 4.13. Found: C, 77.82; H, 8.83; N, 4.06%.
4-(3'-Methyl-3'-octyl)phenolꢑꢀ %ꢉSꢉꢀ ꢎꢋꢁ±ꢎꢋꢃꢀ&ꢒꢏꢉꢍꢀ PP+Jꢓꢀ
PꢉSꢉꢀꢂꢆ±ꢂꢐꢀ&ꢀꢅSKHQ\OFDUEDPDWHꢈꢓꢀ,5ꢀꢅQHDWꢈꢑꢀꢆꢆꢆꢁꢀFP-1; 1H NMR G:
0.65 (t, 3H, J = 7.4 Hz), 0.82 (t, 3H, J = 7.2 Hz), 0.94 and 1.12 (qdd
each, 1H each, Jꢀ ꢀꢎꢋꢉꢏꢊꢀꢁꢉꢋꢊꢀꢋꢉꢇꢀ+]ꢈꢊꢀꢎꢉꢎꢋ±ꢎꢉꢋꢇꢀꢅVHULHVꢀRIꢀPꢊꢀꢋ+ꢈꢊꢀ
1.21 (s, 3H), 1.22 (sextet, 2H, J = 7.2 Hz), 1.46 and 1.62 (dt each, 1H
each, J = 13.0, 4.0 Hz), 1.52 and 1.67 (dq each, 1H each, J = 13.7,
7.4 Hz), 4.64 (s, 1H), 6.76 (d, 2H, J = 8.6 Hz), 7.12 (d, 2H, J = 8.6 Hz);
13C NMR G: 8.6, 14.1, 22.6, 23.6, 23.9, 32.7, 35.7, 40.4, 43.0, 114.6,
127.6, 140.4, 152.8. Anal. Calcd for C15H24O·C7H5NO: C, 77.84; H,
8.61; N, 4.13. Found: C, 78.04; H, 8.85; N, 4.02%.
obtained in reasonable yield although a much longer reaction
period was required for complete demethylation. Another
drawback may be somewhat laborious extraction workup due
to emulsion formation.
During the past decade, microwave heating has been
employed in
a
wide range of transformations,22 and
microwave-assisted cleavage of methyl phenyl ethers was
previously carried out by using neat methanesulfonic acid23 or
clay as solid acidic catalyst.24
Experimental
All boiling and melting points are uncorrected. IR spectra were
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spectrophotometer. 1H and 13C NMR spectra were recorded using a
Bruker Avance 600 spectrometer at 600 and 150.9 MHz, respectively,
in CDCl3 with tetramethylsilane as internal standard. Elemental
analyses were determined on a Carlo Erba EA1108 instrument
and those of new phenol compounds were conducted as the
phenylcarbamate derivatives. All the products have been previously
described in the literatures except compounds listed.
General procedure for methylation of phenols.
Iodomethane (0.25 mL) was added to
a solution of phenol
(2.0 mmol) in dry THF (20 mL) via a syringe followed by NaHMDS
(1 M, 3.0 mL, 3.0 mmol) under Ar. The mixture was stirred at room
temperature for the period given in Table 1 and then poured into
ice-water. The aqueous solution was extracted with CH2Cl2 (20 mL
+ 2 u 10 mL), and the combined extracts were washed with brine,
dried over MgSO4ꢊꢀ¿OWHUHGꢀDQGꢀFRQFHQWUDWHGꢀXQGHUꢀUHGXFHGꢀSUHVVXUHꢉꢀ
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(hexane: EtOAc 49:1).
O-Methyl-4-(3'-methyl-3'-octyl)phenolꢑꢀ %ꢉSꢉꢀ ꢎꢎꢎ±ꢎꢎꢋꢀ&ꢒꢏꢉꢇꢀ PP
Hg; 1H NMR G: 0.65 (t, 3H, J = 7.4 Hz,), 0.82 (t, 3H, J = 7.1 Hz,),
ꢏꢉꢂꢎ±ꢏꢉꢂꢃꢀꢅPꢊꢀꢎ+ꢈꢊꢀꢎꢉꢎꢋ±ꢎꢉꢋꢇꢀꢅVHULHVꢀRIꢀPꢊꢀꢇ+ꢈꢊꢀꢎꢉꢋꢆꢀꢅVꢊꢀꢆ+ꢈꢊꢀꢎꢉꢐꢁꢀDQGꢀ
1.63 (dt each, 1H each, J = 12.6, 4.1 Hz), 1.53 and 1.68 (dt each, 1H
each, J = 13.8, 7.4 Hz), 3.79 (s, 3H, CH3O), 6.83 (d, 2H, J = 8.7 Hz),
7.18 (d, 2H, J = 8.7 Hz); 13C NMR Gꢀ 8.7, 14.1, 22.6, 23.6, 23.9, 32.7,
35.7, 40.4, 43.0, 55.1 (CH3O), 113.2, 127.4, 140.1, 157.1.
Received 12 December 2008; accepted 23 January 2009
Published online: 29 April 2009
References
1
P.G.H. Wuts and T.W. Greene, Protective groups in organic synthesis,
General procedure for demethylation of methyl phenyl ethers
4th edn., Wiley, Hoboken, NJ, 2007.
Microwave heating was carried out by using a household microwave
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Thus, the upper surface of the microwave oven is drilled a hole, in
which carbon-steel tube (inside diameter 20 mm u length 50 mm)
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oven. An adapter which passed through this choke pipe is connected to
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QLWURJHQꢀJDVꢀZDVꢀEXEEOHGꢀLQWRꢀWKHꢀUHDFWLRQꢀPL[WXUHꢀE\ꢀDꢀ7HÀRQꢀWXEHꢀLQOHWꢀ
to prevent bumping. Reaction temperatures were measured by K type
thermocouple immediately after the end of microwave irradiation.
A mixture of anisole (2.0 mmol) and TMSI (1.0 mL) was irradiated
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concentrated under reduced pressure. Saturated aqueous NH4Cl (2 mL)
was added to the residue and the mixture was extracted with CH2Cl2
(20 mL + 2 u 10 mL). The combined extracts were washed with 20%
aqueous Na2S2O3 (10 mL) followed by brine (2 u 10 mL), dried over
MgSO4ꢊꢀ¿OWHUHGꢀDQGꢀFRQFHQWUDWHGꢀXQGHUꢀUHGXFHGꢀSUHVVXUHꢉꢀ7KHꢀUHVLGXHꢀ
ZDVꢀSXUL¿HGꢀE\ꢀFROXPQꢀFKURPDWRJUDSK\ꢀRQꢀVLOLFDꢀJHOꢀꢅKH[DQHꢑꢀ(W2$Fꢀ
19:1). Samples for elemental analysis were prepared by heating a
mixture of the phenol (0.5 mmol) and phenylisocyanate (66 mg, 0.55
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was chromatographed (hexane: EtOAc 19: 1), and the resulant
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4-(2'-Octyl)phenolꢑꢀ %ꢉSꢉꢀ ꢎꢏꢃꢀ&ꢒꢏꢉꢇꢀ PP+Jꢓꢀ PꢉSꢉꢀ ꢃꢂꢉꢇ±ꢂꢏꢀ&ꢀ
(phenylcarbamate); IR (neat): 3325 cm-1; 1H NMR G: 0.85 (t, 3H,
2
3
G.N. Vyas and N.M. Shah, Org. Synth., Collect., 1963, IV, 836.
5
6
7
8
9
I. Tzukervanik, Zh. Obshch. Khim., 1935, 5, 767.
N.B. Nevrekar, Chem. Ind. (London), 1983, 206.
W. Autenrieth, Chem. Ber., 1907, 39, 4098.
10 J.F.W. McOmie and D.E. West, Org. Synth., Collect., 1973, V, 412.
11 N. Sato, unpublished results.
14 D.R. Baghurst and M.P. Mingos, J. Organomet. Chem., 1990, 384, C57.
15 T. Arai, T. Matsumura and T. Oka, Kagaku to Kyoiku, 1993, 41, 278
(Chem. Abstr., 1993, 119, 48677).
16 J.V. Braun, Liebigs Ann. Chem., 1929, 472, 1.
17 R.L. Huang, J. Chem. Soc., 1954, 3084.
18 J. Michel, Bull. Soc. Chim. Belg., 1939, 48, 105.
19 I. Fleming, Synthesis, 1982, 937.
21 M. Sulzbacher, J. Appl. Chem., 1951, 1, 95.
23 A. Fredriksson and S. Stone-Elander, J. Labelled Compd. Radiopharm.,
2002, 45, 529.
24 P. Ramesh and C. Srividhya, Indian J. Heterocycl. Chem., 2005, 15, 157.