Acta Chim. Slov. 2002, 49, 903-908.
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SIMPLE SYNTHETIC STRATEGY TO INHERENTLY CHIRAL CALIX[4]ARENE BY AN ASYMMETRIC CALIX[4]QUINONE AS A KEY
INTERMEDIATE†
Saeed Taghvaei-Ganjali*, Mehdi Shafai, Morteza Khosravi
Department of Chemistry, Islamic azad University North Tehran Branch, Tehran, Iran, P.O. Box: 19585/936, Fax: +98-21-2944678, e-mail: taghvaei@hotmail.com
†
This paper is dedicated to Prof. Dr. Junes Ipaktschi on occasion of his 62th birthday
Received 29-12-2001
Abstract
A simple procedure is developed to synthesize the cone shaped asymmetrically substituted calix[4]arene 5. The resulting chiral calix[4]arene 5 with two hydroxy groups could be used to build up the chiral calix[4]arene hosts.
Introduction
Calix[4]arenes are receptor molecules useful as enzyme mimics.1-3 However, to
mimic the enantioselective behavior of enzymes, it is necessary to use receptors having chiral cavities.4 Although chiral calix[4]arene derivatives can be obtained by attaching chiral residues at the upper or lower rim5-8 of the calixarene skeleton, recent interest9-11 has been focused on the possibility of synthesizing inherently chiral calix[4]arenes, built up of nonchiral subunits still chiral due to the fact that the calixarene molecule is not planar.
Three strategies have been used for the preparation of inherently chiral calix[4]arenes: a) The fragment condensation. b) Asymmetrical arrangement of different substituents at the lower or upper rim. c) Direct introduction of a substituted at the meta position. The first one is based on stepwise synthesis of asymmetric calixarenes having three or four different phenolic units. In most cases this methodology have serious synthetic problems. The second strategy is based on the regio and stereoselective functionalization of convential calixarenes at the lower or upper rim and molecular asymmetry is introduced after the macrolization step. Meta substituted calixarene have been obtained by shinkai in tricarbonylchromium calixarene. Gutsche reported the 1,4-
S. Taghvaei-Ganjali, M. Shafai, M. Khosravi: Simple synthetic strategy to inherently chiral…
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Acta Chim. Slov. 2002, 49, 903-908.
conjugate addition reaction in calix[4]monoquinones to give asymmetrically meta-substituted calix[4]arene.
Results and discussion
In the present communication we describe a very simple method for the preparation
of asymmetrically, meta-substituted calixarene by direct introduction of a iodine atom at
the meta position of one aryl unit.
t-ai                                                          o                                              o
r~
OH
Op    prO-
Opr
\ /
l2, hio3
HCAc CHjCIj
> t-Bu _f    YOpr     pO
Opr
';Opr      prO------u        ir
Opr
t-Bu + t-Bu
The synthesis was done by oxidation of rigidly cone conformation of calix[4]arene triether 112.Oxidation of 1 by HIO3/I2 affords a mixture of quinone 2 and its iodo substituted 3 (in 3:1 ratio). Reduction of 3 produce 5 in quantitative yeild. 1H-NMR spectroscopy of 5 shows the bridge methylene protons (Ar-CH2-Ar) as four doublet of doublet. Also the 13C-NMR spectrum exhibits a set of 24 peaks for aromatic region indicating the asymmetric structure of 5.
2 or 3
OH
NaBH
EIOH
OH
4        k     t-Bu—('        \)Opr     pO------l>        //
\v     II
I     \                  ,
t-Bu   Or t-Bu—('       N>Opr     pO------L        /)-----t-Bu
\^     II
t-Bu
Experimental
Melting points are taken on a Büchi SMP-20 apparatus and are uncorrected. 1H-NMR and 13C-NMR spectra were recorded on a Bruker AM-400MHz in CDCl3 with
t-Bu
t-Bu
t-Bu
3
1
2
t-Bu
4
5
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Acta Chim. Slov. 2002, 49, 903-908.
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Me4Si as an internal standard. Elemental analyses were carried out on Carlo-Erba-Analysor Model 1104. IR spectra were recorded on Bruker IFS 25 spectrophotometer.
Procedure for the preparation of 2 and 3: To solution of 10 mmol of compound 1 in 50 ml acetic acid and 75 ml CH2Cl2 was added concentrated sulfuric acid (2ml), iodine (5gr 19.6mmol) and HIO3 (2.5gr, 14.2mmol). Then reaction mixture was stirred vigorously at room temperature for 8 h. The resulting dark brown solution was decolorized with Na2S2O5 (100ml of a 10% solution) The organic layer was separated, washed three times with water, dried over Na2SO4 and evaporated to dryness. Crystallization of the crude material from ethanol gave yellow crystals of 2 in 63% yield.
Compound 3 was obtained by column chromatography of the remained liquor after crystallization of using CH2Cl2/n-hexane (1:3) as eluent in 32% yield.
5,11,17-Tri-tert-butyl-26,27,28-tris(propoxy)-calix[4]-25-quinone(2), mp. 214-217 °C; ?H (400 MHz; CDCl3) 0.62[3H, t, CH3], 0.86[6H, t, CH3], 0.87[18H, s, C(CH 3)3], 1.18[9H, s, C(CH 3)3], 1.66 [4H, m, CH2], 1.75[2H, m, CH2], 2.94, 3.99[4H, d of d, J=12.7 Hz, ArCH2Ar], 3.35[4H, s, ArCH2Ar], 3.41[4H, t, OCH2], 3.52[2H, t, OCH2], 6.41[2H, d, J=2.4, ArH], 6.44[2H, s, ArH], 6.68[2H, d, J=2.4, ArH], 6.94[2H, s, ArH]; ?C(100MHz) 9.18, 10.70, 22.16, 23.64, 30.86, 31.34, 31.65, 33.78, 34.02, 35.22, 76.09, 76.35, 77.62, 125.63, 126.36, 127.43, 132.77, 133.47, 135.68, 144.97, 145.61, 146.94, 148.25, 148.88, 149.52, 153.86, 154.12, 186.28, 189.18; M/Z(FD) 733(m+,100%). Anal. calcd for C49H64O5 :C, 80.29%; H, 8.80%; found C, 80.14%; H, 9.21%.
5,11,17-Tri-tert-butyl-24-iodo-26,27,28-tris(propoxy)-calix[4]-25-quinone (3), mp. 177-179 °C; ?H (400 MHz; CDCl3) 0.74[3H, t, CH3], 0.84[3H, t, CH3], 0.89[9H, s, C(CH3)3], 0.91[9H, s, C(CH3)3], 0.94[3H, t, CH3], 1.26[9H, s, C(CH3)3], 1.76[2H, m, CH2], 1.88-1.92[4H, m, CH2], 3.04, 4.10[4H, d of d, J=12.8, ArCH2Ar], 3.32, 4.22[2H, d of d, J=13.6, ArCH2Ar], 3.58, 4.22[2H, d of
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d, J=13.7, ArCH2Ar], 3.30-3.86[6H, m, OCH2], 6.49[1H, d, J=2.4, ArH], 6.53[1H, d, J=2.4, ArH], 6.68[1H, d, J=2.4, ArH], 6.78[1H, s, ArH], 6.83[1H, d, J=2.4, ArH], 7.00[1H, d, J=2.4 ArH], 7.02[1H, d, J=2.4, ArH]; ?C(100 MHz) 9.33, 10.21, 10.69, 21.94, 23.52, 23.57, 31.03, 31.12, 31.33, 31.65, 31.72, 33.79, 33.99, 40.79, 75.61, 76.54, 77.24, 125.19, 125.23 125.50, 126.22, 126.28 126.63, 127.02, 127.29, 131.50, 132.69, 133.02, 135.63, 135.72, 144.97, 144.99, 147.28, 153.87, 153.92, 155.25, 181.29, 183.56; M/Z(FD) 859(m+,100%). Anal. calcd for C49H63O5I :C, 68.51%; H, 7.39; found C, 69.10%; H, 7.54%.
Procedure for the preparation of 4 and 5: To solution of 1.36 mmol of 2 or 3 in 25 ml ethanol, sodium borohydride was added (0.12gr, 3.2 mmol). The reaction mixture was stirred at room temperature until the yellowish solution turned colorless. HCl (10ml, 0.2 N) and 50 ml CH2Cl2 was added. The organic layer was separated, washed with water and NaHCO3 (10% solution), dried over Na2SO4 and evaporated to dryness. The product thus obtained was enough pure for subsequent reactions and could be further purified by crystallization in CH2Cl2/MeOH.
5,11,17-Tri-tert-butyl-23,25-dihydroxy-26,27,28-tris(propoxy)-calix[4]aren (4), mp 205-208 °C; ?H(400 MHz; CDCl3) 0.86[18H, s, C(CH3)3], 0.93[3H, t, CH3], 1.08 [6H, t, CH3], 1.33[9H, s, C(CH3)3], 1.89 [4H, m, CH2], 2.31[2H, m, CH2], 3.16, 4.33[4H, d of d, J=13.3, ArCH2Ar], 3.18, 4.37[4H, d of d, J=12.6, ArCH2Ar], 3.72[4H, t, OCH2], 3.84[2H, t, OCH2], 4.22[1H, s, OH], 4.90[1H, s, OH], 6.52[2H, d, J=2.3, ArH], 6.56[2H, d, J=2.3, ArH], 6.58[2H, s, ArH], 7.12[2H, s, ArH]; ?C(100 MHz) 9.49, 10.66, 10.74, 22.34, 23.30, 23.36, 39.63, 31.02, 31.06, 31.08, 31.28, 31.63 34.09, 34.50, 69.47, 76.31, 77.62, 77.91 113.62 123.31, 124.39, 125.07, 125.21, 125.60, 125.67, 130.37, 130.94, 132.07, 132.15, 132.43, 134.41, 135.84, 136.16, 145.11, 145.53, 145.61, 145.73, 146.77,
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147.83, 151.51, 152.07, 153.78; M/Z(FD) 735(m+,100%). Anal. calcd for C49H66O5 :C, 80.07%; H, 9.05%; found C, 80.19%; H, 9.09%.
5,11,17-Tri-tert-butyl-24-iodo-23,25-dihydroxy-26,27,28-tris(propoxy)-calix[4]aren (5), mp 165 °C ; ?H (400 MHz; CDCl3) 0.81[9H, s, C(CH3)3], 0.86[9H, s, C(CH3)3], 0.94[3H, t, CH3], 1.09 [3H, t, CH3], 1.26[3H, t, CH3], 1.35[9H, s, C(CH3)3], 1.82-1.94 [4H, m, CH2], 2.36[2H, m, CH2], 3.18, 4.29[2H, d of d, J=13.3, ArCH2Ar], 3.21, 4.35[2H, d of d, J=12.3, ArCH2Ar], 3.21, 4.38[2H, d of d, J=12.5, ArCH2Ar], 3.81, 4.53[2H, d of d, J=13.8, ArCH2Ar], 3.67-3.76[4H, m, OCH2], 3.84[2H, m, OCH2], 5.05[1H, s, OH], 5.09[1H, s, OH], 6.51[1H, d, J=2.8, ArH], 6.52[1H, d, J=2.8, ArH], 6.58[1H, d, J=2.3, ArH], 6.65[1H, d, J=2.3, ArH], 6.84[1H, s, ArH], 7.15[2H, s, ArH]; ?C(100 MHz) 9.49, 10.66, 10.74, 22.34, 23.30, 23.36, 39.63, 31.02, 31.06, 31.08, 31.28, 31.63, 34.09, 34.50, 69.47, 76.31, 77.62, 77.91, 113.62, 123.31, 124.39, 125.07, 125.21, 125.60, 125.67, 130.37, 130.94, 132.07, 132.15, 132.43, 134.41, 135.84, 136.16, 145.11, 145.53, 145.61, 145.73, 146.77, 147.83, 151.51, 152.07, 153.78; M/Z(FD) 861(m+,100%). Anal. calcd for C49H65O5I :C, 68.36%; H, 7.61; found C, 68.37%; H,7.82%.
Acknowledgements
Saeed Taghvaei-Ganjali is grateful to the Research Council of Islamic azad
University. Generous support from Prof. Dr. J. Ipaktschi, Institute of Organic Chemistry, Giessen University is highly acknowledged.
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References and Notes
1.    S. Shinkai, Pure & Appl. Chem. 1986, 58, 1523.
2.    V. Bohmer, Angew. Chem. 1995, 107, 785.
3.    M. Gardiner and C. Raston, Coord. Chem. Rev. 1997, 166, 1.
4.    W. Saenger, Angew.Chem. Int. Ed. 1980, 19, 344.
5.    K. Iwamoto, K. Araki and S. Shinkai, J. Org. Chem. 1991, 113 , 2385.
6.    C. D. Gutsche and K. C. Nam, J. Am. Chem. Soc. 1988, 110, 6153.
7.    R. Muthukrishnan and C. D. Gutsche, J. Org. Chem. 1979, 44, 3962.
8.    S. Shinkai, Arimura, T. Arimura and H. Satoh, J. Chem. Soc.; Chem. Commun. 1987,1495.
9.    V. Bohmer, A. Volff, W. Vogt; J. Chem. Soc, Chem. Commun. 1990, 968.
10.  V. Bohmer, A. Volff, W. Vogt; J. Org. Chem. 1990, 55, 5665.
11.  G. Andreetti, V. Bohmer, M. Tabatabai; J. Org. Chem. 1993, 58, 4023.
12.  K. Iwamoto; K. Araki and S. Shinkai, Tetrahedron 1991, 25 , 4325.
Povzetek Razvili smo preprosto metodo za sintezo asimetrično substituiranega kaliks[4]arena 5, ki lahko služi za sintezo kiralnih kaliks[4]arenskih gostiteljev.
S. Taghvaei-Ganjali, M. Shafai, M. Khosravi: Simple synthetic strategy to inherently chiral…