E
D. Sang et al.
Letter
Synlett
(19) Giumanini, A. G.; Drusiani, A.; Plessi, L. J. Org. Chem. 1975, 40,
1844.
(20) Koltunov, K. Y.; Repinskaya, I. B. Russ. J. Org. Chem. 1995, 31,
1723.
eugenol can be explained by the fact that AlI3 is more acidic
then AlCl3 and is more prone to coordinating with the o-
methoxy group. See: Bhatt, M. V.; Babu, J. R. Tetrahedron Lett.
1984, 25, 3497.
(21) Koltunov, K. Y.; Repinskaya, I. B.; Borodkin, I. Russ. J. Org. Chem.
2001, 37, 1534.
(22) Koltunov, K. Y.; Walspurger, S.; Sommer, J. Eur. J. Org. Chem.
2004, 4039.
(28) Zehnter, R.; Gerlach, H. Liebigs Ann. 1995, 2209.
(29) Urata, H.; Hu, N. X.; Maekawa, H.; Fuchikami, T. Tetrahedron
Lett. 1991, 32, 4733.
(30) Baggelaar, M. P.; Huang, Y.; Feringa, B. L.; Dekker, F. J.;
Minnaard, A. J. Bioorg. Med. Chem. 2013, 21, 5271.
(23) Characterization Data
Compound 2: white solid; 62%. Rf = 0.77 (PE–EtOAc = 3:1, v/v).
1H NMR (400 MHz, CDCl3): δ = 6.77 (d, J = 8.0 Hz, 1 H), 6.70 (d,
J = 2.0 Hz, 1 H), 6.61 (dd, J1 = 8.0 Hz, J2 = 2.0 Hz, 1 H), 5.20 (s, 1
H), 5.07 (s, 1 H), 2.47 (t, J = 7.6 Hz, 2 H), 1.58 (sext, J = 7.6 Hz, 2
H), 0.91 (t, J = 7.6 Hz, 3 H). 13C NMR (100 MHz, CDCl3): δ =
143.23, 141.14, 136.09, 120.90, 115.55, 115.19, 37.33, 24.68,
13.78.
(31) Khrimian, A. P.; DeMilo, A. B.; Waters, R. M.; Liquido, N. J.;
Nicholson, J. M. J. Org. Chem. 1994, 59, 8034.
(32) (a) The effectiveness of AlCl3–pyridine is limited in the demeth-
ylation of eugenol, see: ‘Example XXVII’ of ref. 8. (b) It is a sur-
prise that Lange had not extended AlCl3–pyridine to AlBr3-pyri-
dine and AlI3-pyridine while other Lewis acids such as BBr3,
FeCl3, and ZnCl2 had been screened, see ref.
8 and 33.
Compound 3: Purification of 3 by column chromatography was
unsuccessful. It is thermally unstable and decomposed during
an attempted vacuum distillation at above 110 °C. Yellow oil
(contains about 10% of unidentified impurity); 17%. Rf = 0.62
(PE–EtOAc = 3:1, v/v). 1H NMR (400 MHz, CDCl3): δ = 6.87–6.83
(m, 1 H), 6.70–6.66 (m, 2 H), 5.53 (s, 1 H), 5.17 (s, 1 H), 4.30
(sext, J = 6.8 Hz, 1 H), 3.89 (s, 3 H), 3.22 (dd, J1 = 14.0 Hz, J2 = 7.2
Hz,1 H), 2.98 (dd, J1 = 14.0 Hz, J2 = 7.6 Hz, 1 H), 1.88 (d, J = 7.8 Hz,
3 H). 13C NMR (100 MHz, CDCl3): δ = 116.42, 114.48, 131.72,
121.84, 114.37, 111.59, 56.02, 49.22, 29.39, 27.99. ESI-HRMS:
m/z calcd for C10H13O2I: 291.9960; found: 291.9955 [M+].
Compound 4: white solid; 22%. Rf = 0.35 (PE–EtOAc = 3:1, v/v).
1H NMR (400 MHz, CDCl3): δ = 6.79 (d, J = 8.0 Hz, 1 H), 6.71 (d,
J = 2.0 Hz, 1 H), 6.62 (dd, J1 = 8.0 Hz, J2 = 2.0 Hz, 1 H), 6.26 (s, 1
H), 5.17 (s, 1 H), 4.27 (sext, J = 7.2 Hz, 1 H), 3.17 (dd, J1 = 14.0 Hz,
J2 = 7.2 Hz, 1 H), 2.93 (dd, J1 = 14.0 Hz, J2 = 7.2 Hz,1 H), 1.87 (d,
J = 7.2 Hz, 3 H). 13C NMR (100 MHz, CDCl3): δ = 143.3, 142.1,
133.0, 121.7, 116.1, 115.4, 48.7, 29.1, 28.0. MS (EI): m/z (%) =
278 (41) [M+], 151 (100). HRMS (EI): m/z calcd for C9H11O2I:
277.9804; found: 277.9801 [M+].
(c) Hydrogenation and hydrofluorination were observed when
treating eugenol methyl ether with HF–pyridine, see: Khrimian,
A. P.; DeMilo, A. B.; Waters, R. M.; Liquido, N. J.; Nicholson, J. M.
J. Org. Chem. 1994, 59, 8034.
(33) Lange, R. G. J. Org. Chem. 1962, 27, 2037.
(34) General Procedure
To a solution of AlI3 (36.6 mmol, 1.1 equiv) in MeCN (100 mL)
was added dropwise a solution of pyridine (12.2 g, 154.2 mmol,
4.6 equiv) and eugenol (5.4 g, 33.0 mmol). The mixture was
stirred at 80 °C for 18 h. After cooling to room temperature, the
mixture was quenched with aq HCl (2 mol/L, 50 mL), and was
extracted with EtOAc (4 × 50 mL). The combined organic phases
were washed with brine and dried by MgSO4. After evaporation
of solvents by a rotary evaporator, the residue was purified
through flash column chromatography to afford 5 as a white
1
solid (4.9 g, 99%). Rf = 0.46 (PE–EtOAc = 3:1, v/v). H NMR (400
MHz, CDCl3): δ = 6.80 (d, J = 8.0 Hz, 1 H), 6.72 (d, J = 2.0 Hz, 1 H),
6.63 (dd, J1 = 8.0 Hz, J2 = 2.0 Hz, 1 H), 6.10 (br s, 2 H), 5.92 (ddt,
J1 = 17.2 Hz, J2 = 10.4 Hz, J2 = 6.8 Hz, 1 H), 5.05 (dq, J1 = 16.8 Hz,
J2 = 1.6 Hz, 1 H), 5.03 (dq, J1 = 10.0 Hz, J2 = 1.6 Hz, 1 H), 3.26 (d, J
= 6.4 Hz, 1 H). 13C NMR (100 MHz, CDCl3): δ = 143.35, 141.54,
137.65, 133.60, 121.33, 116.09, 115.80, 115.71, 39.50.
(35) Eugenol methyl ether can be exhaustively demethylated by AlI3.
Similarly, 5-allylresorcinol can be prepared by treating 5-allyl-
1,3-dimethoxybenzene with AlI3, see: Coolen, H. K.; Meeuwis, J.
A.; Van Leeuwen, P. W.; Nolte, R. J. J. Am. Chem. Soc. 1995, 117,
11906.
(24) Doyle, M. P.; McOsker, C. C.; West, C. T. J. Org. Chem. 1976, 41,
1393.
(25) Nenitzescu, C. D.; Dragan, A. Ber. Dt. Chem. Ges. 1933, 66, 1892.
(26) Schmerling, L. Ind. Eng. Chem. 1948, 40, 2072.
(27) Treating eugenol with AlCl3 in hexane affords 4-(2-chloropro-
pyl)-2-methoxyphenol and 4-propyl-2-methoxyphenol as two
isolable intermediates, suggesting that hydrogen–halogen
exchange proceeds faster than AlCl3-induced demethylation of
eugenol. The marked difference between AlCl3 and AlI3 toward
(36) Buchanan, D. H.; Takemura, N.; Sy, J. N. O. J. Org. Chem. 1986, 51,
4291.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–E