10.1002/ejoc.201801731
European Journal of Organic Chemistry
COMMUNICATION
in good yields (entry 1 and 2, Table 5). Under similar reaction
conditions, benzaldehyde (1a) reacted readily with L-(+)-diethyl
tartrate (27) to furnish the C2-symmetric benzylidene acetal 30[37]
in very good yield (entry 3, Table 5).
hexane as eluent to furnish benzylidene acetal 11a[23] (3.59 g,
93%) as a colorless liquid.
Acknowledgements
Table 5: Synthesis of optically active acetals catalyzed by Dowex 50WX8 at
room temperature.
We thank DST-SERB (EMR/2016/004040), India, for financial
support and DST-FIST for providing instruments facilities. N.R.R
thanks CSIR-New Delhi for research fellowship.
Keywords: protecting group. benzylidene acetal. solid acid
catalyst. room temperature reaction. water scavenger.
[1] a) T. W. Greene, P. G. M. Wuts, Protective Groups in Organic
Synthesis; John Wiley & Sons: New York, 1999; b) P. J. Kocienski,
Protecting Groups; Georg Thieme Verlag: New York, 1994; c) M.
Schelhaas, H. Waldmann, Angew. Chem. Int. Ed. 1996, 35, 2056-
2083; Angew. Chem. 1996, 108, 2192-2219.
[2] Z. Y. Zhang, C.-H. Wong, In Carbohydrates in Chemistry and Biology;
(Eds.: B. Ernst, G. W. Hart, P. Sinay), Wiley-VCH: Weinheim,
Germany, 2000, p.685.
[3] a) P. J. Garegg, Pure Appl. Chem., 1984, 56, 845; b) S. Hanessian in
Preparative Carbohydrate Chemistry; (Ed.: S. Hanessian), Marcel
Dekker, Inc., New York, 1997, 53-57.
[4] a) S. Hanessian, A. P. A. Staub, Tetrahedron Lett. 1973, 14, 3551-
3554; b) N. Chidambaram, S. Bhat, S. Chandrasekaran, J. Org.
Chem. 1992, 57, 5013-5015; c) F. E. Ziegler, J. S. Tung, J. Org.
Chem. 1991, 56, 6530-6537; d) S. S. Meng, Y. Liang, K. S. Cao, L.
Zou, X. B. Lin, H. Yang, K. N. Houk, W. H. Zheng, J. Am. Chem. Soc.
2014, 136, 12249-12252.
[a] Isolated yield.
[5] a) A. Banerjee, S. Senthilkumar, S. Baskaran. Chem. Eur. J. 2016,
22, 902-906; b) P. S. Kumar, A. Banerjee, S. Baskaran. Angew.
Chem. Int. Ed. 2010, 49, 804-807; Angew. Chem. 2010,122, 816-819;
c) P. S. Kumar, A. Aravind, S. Baskaran, Tetrahedron Lett. 2007, 48,
1175-1178; d) A. Aravind, S. K. Mohanty, T. V. Pratap, S. Baskaran,
Tetrahedron Lett. 2005, 46, 2965-2968.
[6] a) S. Manabe, K. Ishii, Y. Ito, J. Org. Chem. 2007, 72, 6107-6115; b)
S. Jonke, K. G. Liu, R. R. Schmidt, Chem. Eur. J. 2006, 12, 1274-
1290; c) C.‐C. Wang, S.‐Y. Luo, C.‐R. Shie, S.‐C. Hung,
Org. Lett. 2002, 4, 847-849; d) E. Lee, C. M. Park, J. S. Yun, J. Am.
Chem. Soc. 1995, 117, 8017-8018; e) R. Johnsson, M. Ohlin, U.
Ellervik, J. Org. Chem., 2010, 75, 8003-8011.
[7] a) A. Aravind, P. S. Kumar, M. G. Sankar, S. Baskaran, Eur. J. Org.
Chem. 2011, 6980-6988; b) A. Aravind, M. G. Sankar, B. Varghese,
S. Baskaran, J. Org. Chem. 2009, 74, 2858-2861; c) P. S. Kumar, S.
Baskaran, Tetrahedron Lett. 2009, 50, 3489-3492; d) A. Aravind, S.
Baskaran, Tetrahedron Lett. 2005, 46, 743-745; e) V. Balakumar, A.
Aravind, S. Baskaran, Synlett 2004, 04, 647-650.
[8] For benzylidene acetal hydrolysis, see: a) K. S. Kim, Y. H. Song, B.
H. Lee, C. S. Hahn, J. Org. Chem. 1986, 51, 404-407; b) A.
Geetanjali, A. K. Misra, Tetrahedron Lett. 2006, 47, 3653-3658; c) Y.
Niu, N. Wang, X. Cao, X.-S. Ye, Synlett 2007, 13, 2116-2120; d) D.
S. Bose, B. Jayalakshmi, A. V. Narsaiah, Synthesis 2000, 67-68; e)
P. S. Kumar, G. D. K. Kumar, S. Baskaran, Eur. J. Org. Chem. 2008,
6063-6067.
Conclusions
In summary, a simple and metal-free method has been
developed for the efficient synthesis of benzylidene acetal from
functionalized diols at room temperature. The salient features of
this method are, i) this direct method is operationally simple,
scalable and does not require Dean-Stark apparatus; ii) in this
room temperature method, Cl3CCN serves as a reaction medium
as well as water scavenger; iii) the solid acid Dowex 50WX8
catalyst can be readily recovered and recycled; iv) under the
reaction conditions, unsaturated aldehydes reacted smoothly to
furnish the corresponding acetals in very good yields; v) the
carbohydrate substrates and optically active diols reacted readily
to afford the corresponding acetals in good yields and vi) Labile
functional groups, like N-Boc, N-Cbz, -OTBDMS, -OBn, -N3 and
acetonide are found to be stable under the reaction conditions.
Since our room temperature direct acetalization protocol is
simple and efficient, it will find a wide application in organic
synthesis.
[9] a) E. Wenkert, T. E. Goodwin, Synth. Commun. 1977, 7, 409-415; b)
A. F. B. Cameron, J. S. Hunt, J. F. Oughton, P. A. Wilkinson, B. M.
Wilson, J. Chem. Soc. 1953, 3864-3869.
[10] a) A. Clerici, N. Pastori, O. Porta, Tetrahedron 1998, 54, 15679-
15690; b) A. L. Gemal, J.-L. Luche, J. Org. Chem. 1979, 44, 4187-
4189; c) W. W. Zajac, K. J. Byrne, J. Org. Chem. 1970, 35, 3375-
3377; d) M. Kurihara, W. Hakamata, J. Org. Chem. 2003, 68, 3413-
3415; e) S. H. Anderson, H.-S. Uh, Synth. Commun. 1973, 3, 125-
131; f) T. Tsunoda, M. Suzuki, R. Noyori, Tetrahedron Lett. 1980, 21,
1357-1358.
[11] a) B. T. Gregg, K. C. Golden, J. F. Quinn, Tetrahedron 2008, 64,
3287-3295; b) R. Mahrwald, J. Prakt. Chem. 1994, 336, 361-362; c)
H. Firouzabadi, N. Iranpoor, B. Karimi, Synlett 1999, 321-323.
[12] a) C. González-Arellano, S. Deb, R. Luque, Catal. Sci. Technol.,
2014, 4, 4242-4249; b) U. Azzena, M. Carraro, A. D. Mamuye, I.
Murgia, L. Pisano, G. Zedde, Green Chem. 2015, 17, 3281-3284.
[13] A. Piasecki, Tetrahedron 1984, 40, 4893-4896.
[14] S. A. Patwardhan, S. Dev, Synthesis 1974, 348-349.
[15] C.-T. Chen, S.-S. Weng, J.-Q. Kao, C.-C. Lin, M.-D. Jan, Org. Lett.
2005, 7, 3343-3346.
[16] a) R. R. Kale, C. M. McGannon, C. Fuller-Schaefer, D. M. Hatch, M.
J. Flagler, S. D. Gamage, A. A. Weiss, S. S. Iyer, Angew. Chem. Int.
Ed. 2008, 47, 1265-1268; Angew. Chem. 2008, 120, 1285-1288; b) R.
R. Schmidt, J. Michel, Angew. Chem. Int. Ed. 1980, 19, 731-732;
Angew. Chem. 1980, 92, 763-764.
Experimental Section
Gram scale synthesis of compound 11a: To a stirred solution
of pinacol (10) (2.43 g, 20.6 mmol) in Cl3CCN (25 mL) at room
temperature under N2 atmosphere were added benzaldehyde
(1a) (2.0 g, 18.8 mmol) and 50 wt% of DOWEX 50WX8 (1.0 g).
Reaction mixture was stirred for 5h at room temperature. The
catalyst DOWEX was recovered by filtration and washed with
dichloromethane. The combined organic solvent was evaporated
under reduced pressure and the residue was diluted with
dichloromethane (20 mL) and washed successively with water (2
X 20 mL) and brine solution (20 mL). The organic layer was
dried over anhydrous Na2SO4, filtered and concentrated under
reduced pressure. The crude product was purified by column
chromatography over silica gel using 5-10% ethyl acetate-
[17] T. L. Ho, C. M. Wong, J. Org. Chem. 1973, 38, 2241-2242.
This article is protected by copyright. All rights reserved.