Synlett 2017; 28(01): 138-142
DOI: 10.1055/s-0035-1588889
letter
© Georg Thieme Verlag Stuttgart · New York

Pyridine Improves Aluminum Triiodide Induced Selective Cleavage of Alkyl o-Hydroxyphenyl Ethers: A Practical and Efficient Procedure for the Preparation of Hydroxychavicol by Demethyl­ation of Eugenol

Dayong Sang
a   Jingchu University of Technology, 33 Xiangshan Road, Jingmen, Hubei 448000, P. R. of China   Email: tianjuan2015@hotmail.com
,
Ming Yao
a   Jingchu University of Technology, 33 Xiangshan Road, Jingmen, Hubei 448000, P. R. of China   Email: tianjuan2015@hotmail.com
,
Juan Tian*
a   Jingchu University of Technology, 33 Xiangshan Road, Jingmen, Hubei 448000, P. R. of China   Email: tianjuan2015@hotmail.com
,
Xiaoman Chen
b   Wuhan Institute of Bioengineering, 1 Hanshi Road, Wuhan, Hubei 430415, P. R. of China
,
Li Li
a   Jingchu University of Technology, 33 Xiangshan Road, Jingmen, Hubei 448000, P. R. of China   Email: tianjuan2015@hotmail.com
,
Hongju Zhan
a   Jingchu University of Technology, 33 Xiangshan Road, Jingmen, Hubei 448000, P. R. of China   Email: tianjuan2015@hotmail.com
,
Linhong You
b   Wuhan Institute of Bioengineering, 1 Hanshi Road, Wuhan, Hubei 430415, P. R. of China
› Author Affiliations
Further Information

Publication History

Received: 14 August 2016

Accepted after revision: 06 September 2016

Publication Date:
29 September 2016 (online)


Abstract

Demethylation of eugenol with aluminum triiodide is complicated by an unexpected hydrogenation side reaction. The hydrogenation proceeds through a cascade deprotonation, hydroiodination, and hydrogen–halogen exchange process, and can be prevented by suppressing the hydroiodination in advance. A practical demethylation procedure is thus developed that delivers hydryoxychavicol in essentially quantitative yield by using pyridine as an additive. The method is selective towards cleaving alkyl o-hydroxyphenyl ethers and is compatible with a variety of functional groups.

 
  • References and Notes

  • 1 Mula S, Banerjee D, Patro BS, Bhattacharya S, Barik A, Bandyopadhyay SK, Chattopadhyay S. Bioorg. Med. Chem. 2008; 16: 2932
  • 2 Amonkar AJ, Nagabhushan M, D'Souza AV, Bhide SV. Food Chem. Toxicol. 1986; 24: 1321
  • 3 Sharma S, Khan IA, Ali I, Ali F, Kumar M, Kumar A, Johri RK, Abdullah ST, Bani S, Pandey A, Suri KA, Gupta BD, Satti NK, Dutt P, Qazi GN. Antimicrob. Agents Chemother. 2009; 53: 216
  • 4 Gundala SR, Yang C, Mukkavilli R, Paranjpe R, Brahmbhatt M, Pannu V, Cheng A, Reid MD, Aneja R. Toxicol. Appl. Pharmacol. 2014; 280: 86
  • 5 Chang MC, Uang BJ, Tsai CY, Wu HL, Lin BR, Lee CS, Chen YJ, Chang CH, Tsai YL, Kao CJ, Jeng JH. Br. J. Pharmacol. 2007; 152: 73
    • 6a Yadav Y, Owens EA, Sharma V, Aneja R, Henary M. Eur. J. Med. Chem. 2014; 75: 1
    • 6b Liu HX, Tan HB, He MT, Li L, Wang YH, Long CL. Tetrahedron 2015; 71: 2369
    • 6c Fache F, Suzan N, Piva O. Tetrahedron 2005; 61: 5261
    • 6d Zhao HP, Brandt GE, Galam L, Matts RL, Blagg BS. J. Bioorg. Med. Chem. Lett. 2011; 21: 2659
    • 6e Bandyopadhyay S, Pal BC, Parasuraman J, Roy S, Chakrabotry JB, Mukherjee IC, Mahato SK, Konar A, Rakshit S, Mandal L, Ganguly D, Paul K, Manna A, Vinayagam J, Pal C. 793 423, 2010
  • 7 Arifin B, Tang DF, Achmadi SS. Indo. J. Chem. 2015; 15: 77
  • 8 Lange RG. US 3256336, 1966
  • 9 Shenoy NR, Choughuley AS. U. J. Agric. Food Chem. 1989; 37: 721
  • 10 Kraft P, Eichenberger W. Eur. J. Org. Chem. 2003; 3735
  • 11 Zhao HP, Brandt GE, Galam L, Matts RL, Blagg BS. J. Bioorg. Med. Chem. Lett. 2011; 21: 2659
  • 12 Bhatt MV, El-Morey SS. Synthesis 1982; 1048
  • 13 Coolen HK. A. C, Meeuwis JA. M, Van Leeuwen PW. N. M, Nolte RJ. M. J. Am. Chem. Soc. 1995; 117: 11906
  • 14 Anderson SG. B. Synthesis 1985; 437
  • 15 For a review on applications of AlI3 and AlI3–TBAI in ether cleavage, see: Tian J, Sang DY. ARKIVOC 2015; (vi): 446
  • 16 Deffieux D, Gossart P, Quideau S. Tetrahedron Lett. 2014; 55: 2455
    • 17a Ozanne A, Pouységu L, Depernet D, Francois B, Quideau S. Org. Lett. 2003; 5: 2903
    • 17b Pouységu L, Sylla T, Garnier T, Rojas LB, Charris J, Deffieux D, Quideau S. Tetrahedron 2010; 66: 5908
  • 18 Nilov DI, Vasilyev AV. Tetrahedron Lett. 2015; 56: 5714
  • 19 Giumanini AG, Drusiani A, Plessi L. J. Org. Chem. 1975; 40: 1844
  • 20 Koltunov KY, Repinskaya IB. Russ. J. Org. Chem. 1995; 31: 1723
  • 21 Koltunov KY, Repinskaya IB, Borodkin I. Russ. J. Org. Chem. 2001; 37: 1534
  • 22 Koltunov KY, Walspurger S, Sommer J. Eur. J. Org. Chem. 2004; 4039
  • 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, J 1 = 8.0 Hz, J 2 = 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. 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, J 1 = 14.0 Hz, J 2 = 7.2 Hz,1 H), 2.98 (dd, J 1 = 14.0 Hz, J 2 = 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, J 1 = 8.0 Hz, J 2 = 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, J 1 = 14.0 Hz, J 2 = 7.2 Hz, 1 H), 2.93 (dd, J 1 = 14.0 Hz, J 2 = 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+].
  • 24 Doyle MP, McOsker CC, West CT. J. Org. Chem. 1976; 41: 1393
  • 25 Nenitzescu CD, 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-chloropropyl)-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 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 MV, Babu JR. Tetrahedron Lett. 1984; 25: 3497
  • 28 Zehnter R, Gerlach H. Liebigs Ann. 1995; 2209
  • 29 Urata H, Hu NX, Maekawa H, Fuchikami T. Tetrahedron Lett. 1991; 32: 4733
  • 30 Baggelaar MP, Huang Y, Feringa BL, Dekker FJ, Minnaard AJ. Bioorg. Med. Chem. 2013; 21: 5271
  • 31 Khrimian AP, DeMilo AB, Waters RM, Liquido NJ, Nicholson JM. J. Org. Chem. 1994; 59: 8034
    • 32a The effectiveness of AlCl3–pyridine is limited in the demethylation of eugenol, see: ‘Example XXVII’ of ref. 8.
    • 32b It is a surprise that Lange had not extended AlCl3–pyridine to AlBr3-pyridine and AlI3-pyridine while other Lewis acids such as BBr3, FeCl3, and ZnCl2 had been screened, see ref. 8 and 33.
    • 32c Hydrogenation and hydrofluorination were observed when treating eugenol methyl ether with HF–pyridine, see: Khrimian AP, DeMilo AB, Waters RM, Liquido NJ, Nicholson JM. J. Org. Chem. 1994; 59: 8034
  • 33 Lange RG. 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 solid (4.9 g, 99%). Rf = 0.46 (PE–EtOAc = 3:1, v/v). 1H 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, J 1 = 8.0 Hz, J 2 = 2.0 Hz, 1 H), 6.10 (br s, 2 H), 5.92 (ddt, J 1 = 17.2 Hz, J 2 = 10.4 Hz, J 2 = 6.8 Hz, 1 H), 5.05 (dq, J 1 = 16.8 Hz, J 2 = 1.6 Hz, 1 H), 5.03 (dq, J 1 = 10.0 Hz, J 2 = 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 HK, Meeuwis JA, Van Leeuwen PW, Nolte RJ. J. Am. Chem. Soc. 1995; 117: 11906
  • 36 Buchanan DH, Takemura N, Sy JN. O. J. Org. Chem. 1986; 51: 4291