Molecular iodine: An efficient and environment-friendly catalyst for the synthesis of calix[4]resorcinarenes

Article abstract of DOI:10.1016/j.crci.2013.10.017

Iodine catalyzes the cyclocondensation of various aldehydes with resorcinol to give tetrameric cyclic products, resorcinarenes. Through the reaction of resorcinol with aromatic aldehydes, the product is obtained as a mixture of two isomers, the all-cis is

Full text of DOI:10.1016/j.crci.2013.10.017

C. R. Chimie 17 (2014) 890–893
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Preliminary communication/Communication
Molecular iodine: An efficient and environment-friendly
catalyst for the synthesis of calix[4]resorcinarenes
´
´
`
Iode moleculaire : un catalyseur efficace et ecologique pour la synthese de
´
`
calix[4]resorcinarenes
*
Fatemeh Darvish , Shima Khazraee
Department of Chemistry, Faculty of Science, K.N. Toosi University of Technology, Tehran 15875-4416, Iran
A R T I C L E I N F O
A B S T R A C T
Article history:
Iodine catalyzes the cyclocondensation of various aldehydes with resorcinol to give
tetrameric cyclic products, resorcinarenes. Through the reaction of resorcinol with
aromatic aldehydes, the product is obtained as a mixture of two isomers, the all-cis isomer
(rccc) and the cis-trans-trans isomer (rctt), whereas a single diastereomer, the all-cis, is
formed with aliphatic aldehydes. Besides excellent isolated yields, the use of iodine makes
this procedure simple, convenient, cost-effective and practical.
Received 18 May 2013
Accepted after revision 28 October 2013
Available online 1 July 2014
Keywords:
Calix[4]resorcinarenes
Iodine
ß 2013 Acade´mie des sciences. Published by Elsevier Masson SAS. All rights reserved.
Catalysts
Condensation
Macrocycle
´
´
R E S U M E
L’iode catalyse la cyclo-condensation de divers alde´hydes avec le re´sorcinol afin de
Mots cle´s :
Calix[4]resorcinare`nes
Iode
´
´
´
´
´
`
preparer des produits cycliques tetrameriques appeles resorcinarenes. Les produits
´
´
`
obtenus avec des aldehydes aromatiques presentent deux isomeres (RCCC et RCTT), tandis
Catalyseurs
Condensation
Macrocycle
qu’un seul diaste´re´oisome`re (RCCC) est forme´ avec les alde´hydes aliphatiques. Ainsi, cette
´
nouvelle procedure faisant intervenir l’iode comme catalyseur constitue une nouvelle
´
`
methode simple et rentable pour l’obtention de calix[4]resorcinarenes.
ß 2013 Acade´mie des sciences. Publie´ par Elsevier Masson SAS. Tous droits re´serve´s.
1. Introduction
applied as stationary phases in HPLC [2] and chiral
capillary gas chromatography for the separation of
Calix[4]resorcinarenes (resorcinarenes) are widespread
cyclic tetrameric host compounds for ions, sugars and
organic molecules; as a consequence they are used as
starting materials for a variety of cavitands or other
macrocyclic host molecules[1]. They have also been
positional isomers of substituted benzenes [3]. Further-
more, they can exhibit liquid-crystalline behavior
through the appropriate choice of the R groups on the
resorcinarene [4]. Fig. 1 represents the general procedure
for the formation of calix[4]resorcinarenes by cyclocon-
densation of resorcinol and aldehydes.
a
The most common synthetic method still involves
mineral acid catalysis of this condensation in hot alcohol
solution [5], in which the use of large quantities of
concentrated HCl leads to excessive waste streams that are
*
Corresponding author.
E-mail addresses: darvish@kntu.ac.ir,
darvich_f_m@yahoo.com (F. Darvish).
1631-0748/$ – see front matter ß 2013 Acade´mie des sciences. Published by Elsevier Masson SAS. All rights reserved.
http://dx.doi.org/10.1016/j.crci.2013.10.017

F. Darvish, S. Khazraee / C. R. Chimie 17 (2014) 890–893
891
HO
OH
OH
OH
HO
O
HO
OH
R
R
catalyst
+
R
H
R
R
HO
HO
OH
Fig. 1. Synthesis of calix[4]resorcinarenes by cyclocondensation of resorcinol and aldehydes.
Table 1
environmentally unfriendly and expensive to deal with. A
solvent-free synthesis method of calix[4]resorcinarenes
using p-TsOH as the catalyst has also been reported [6].
This convincing green approach was unsuccessful because
the longer the alkyl chain of the aldehyde, the lower the
reaction yield. Classical Lewis acids like BF3.OEt2, AlCl3 and
SnCl4 have been used only for the synthesis of aromatic
aldehyde-derived resorcinarenes [7]. Unfortunately, this
method has several disadvantages such as the use of large
quantities of these Lewis acids to obtain good yields of the
product and the sensitivity of these catalysts to water,
which results in acidic and metal oxide by-products upon
aqueous work-up. More recently, triflate-based catalysts
such as ytterbium(III) triflate [8] and bismuth(III) triflate
[9] have been introduced for this condensation. Expensive
preparation and corrosive starting material to prepare
triflate salt could be one of the disadvantages of this
method. The use of lanthanide sulfonate [10] and the
microwave-assisted synthesis of resorcinarene in the
presence of HCl and tungstophosphoric acid (TPA) has
also been reported [11]. Therefore, the development of
new synthetic methods would be of special interest.
Molecular iodine as a mild Lewis acid has received
considerable attention as an inexpensive, non-toxic,
readily available and environmentally friendly catalyst
in organic and pharmaceutical syntheses [12]. It is also
highly tolerant to air as well as to moisture. Recent studies
indicate that iodine can be effectively used as a catalyst for
acetylation [13], protections and deprotections, oxida-
tions, three-component synthesis of protected homoallylic
amines [14], direct oxidative conversion of alkyl halides
into nitriles, synthesis of bis(indolyl) methanes [15],
alkylation of active methylene compounds [16], and
synthesis of amidophenol [17]. We now report the utility
of iodine as an efficient catalyst for the condensation of
aldehydes and resorcinol to give the corresponding
resorcinarenes in excellent yields.
The effect of different amounts of iodine for the synthesis of 1a (R = C4H9).
Isolated yield [%]
Iodine [mmol%]
Entry
—
0
5
1
2
3
4
73
80
95
10
20
Conditions: pentanal (1 mmol) and resorcinol (1 mmol) in presence of
different catalytic amounts of catalyst at 80 8C in ethanol for 2 h.
optimize the reaction temperature, the synthesis of
compound 1a was carried out in ethanol at room
temperature, 30, 50, and 78 8C, respectively (Table 2).
We found that below the reflux temperature of ethanol, no
reaction occurred. Therefore, the desired reaction tem-
perature should be 78 8C (Table 2, entry 4).
We carefully analyzed the 1H NMR spectra of 1, 2, 3
(aliphatic) and 4, 5,
reaction of resorcinol with aromatic aldehydes in the
presence of iodine formed a mixture of diastereomers
(Fig. 2). With benzaldehyde, the product was obtained as a
mixture of diastereomers, all-cis (rccc, C4 ) isomer (a) and
the cis-trans-trans (rctt, C2 ) isomer (b). The 1H NMR
spectrum of benzaldehyde-derived resorcinarene showed
one singlet at
and two singlets at
aromatic protons Hin (each 2 H), indicating that the C2
isomer had been produced. An equivalent single resonance
for the four ortho protons of resorcinol rings at = 6.12 and
the four meta protons at = 6.33 were consistent with
those previously reported for the C4 isomer. Other
aromatic aldehydes such as 4-hydroxybenzaldehyde and
4-methoxybenzaldehyde were also tested.
6 (aromatic). The condensation
v
v
d
= 5.37 for the bridge benzylic protons (4 H)
d
= 5.55 and 6.11 for the intra-annular
v
d
d
v
In both cases, the corresponding resorcinarenes were
a mixture of C4 and C2 isomers as well. For the 1H NMR
v
v
Table 2
Optimization of temperature for the synthesis of 1a (R = C4H9).
2. Results and discussion
Isolated yield [%]
Temp. [8C]
Entry
Initially the reaction between pentanal and resorcinol
was used as a model reaction. To optimize the catalyst’s
loading, amounts of 0, 5, 10, and 20 mol% of iodine were
tested, respectively. The results are summarized in Table 1.
A 20 mol% loading of iodine was sufficient to obtain the
best yield of resorcinarene 1a (Table 1, entry 4). To
—
r.t.
30
50
78
1
2
3
4
—
—
95
Conditions: pentanal (1 mmol) and resorcinol (1 mmol) in the presence of
a catalytic amount of catalyst (20 mol%) in ethanol for 2 h.

892
F. Darvish, S. Khazraee / C. R. Chimie 17 (2014) 890–893
HO
HO
OH
OH
OH
OH
OH
OH
HO
HO
HO
HO
O
R
HO
OH
R
R
R
R
I2 (20 mol%)
EtOH/ heat
+
+
R
H
R
R
R
HO
HO
OH
OH
a
b
1 R = C4H9, t = 120 min, Yield = 95%, (1a:1b = 1:0)
2 R = C8H17, t = 95 min, Yield = 86%, (2a:2b = 1:0)
3 R = C9H19, t = 130 min, Yield = 85%, (3a:3b = 1:0)
4 R = Ph, t = 73 min, Yield = 98%, (4a:4b = 3:1)
5 R = 4-OH-Ph, t = 68 min, Yield = 97%, (5a:5b = 1:1)
6 R = 4-CH3O-Ph, t = 70 min, Yield = 97%, (6a:6b =2:1)
Fig. 2. Condensation reaction of resorcinol with aromatic aldehydes in the presence of iodine, affording a mixture of diastereomers.
spectrum of resorcinarene 5, one singlet at
two singlets at = 5.92 and 6.09 indicated the presence of
the rctt isomer, while a single resonance for the four
ortho protons of resorcinol rings at = 6.08 and the four
meta protons at = 6.31 proved the existence of the rccc
configuration. The thermodynamically favored all-cis
isomer (via single resonances at = 6.11 and 6.30)
besides the cis-trans-trans isomer (based on singlet
resonances at = 5.45, 5.55 and 6.11) were clearly
identified in the 1H NMR spectrum of resorcinarene 6.
The ratio of diastereomers after completion of the
reaction (as judged by the disappearance of the starting
materials by TLC) was obtained by integration of the
signals of the benzylic hydrogens of the rccc isomer to
the signals of the benzylic hydrogens of the rctt isomer.
For the resorcinarenes derived from aliphatic substrates,
the tetrameric nature of the products was only that of the
all-cis (rccc) isomer.
d
= 5.42 and
3. Conclusion
d
In summary, we have developed an alternative and
simple method for the preparation of calix[4]resorcinar-
enes in the presence of iodine as a catalyst. The advantages
of this method include reasonable reaction time, the use of
very cheap and easy available catalyst, excellent yields,
and simple workup. The reactions could also be carried out
in air, since iodine is not moisture sensitive. Consequently,
this method has wide scope for further applications.
d
d
d
d
4. Experimental
4.1. General remarks
All the chemicals were purchased from Merck Chemi-
cals and used without further purification. The melting
points were taken in open capillary tubes with an
Electrothermal 9100 Apparatus. FT–IR (KBr) spectra were
recorded on an ABB FT-IR FTLA 2000 spectrometer. 1H NMR
spectra were run on a Bruker DRX-300 (300 MHz) AVANCE
instrument using TMS as an internal standard and DMSO-
Finally, a comparison was made between the synthesis
of resorcinarene 4 and other reported procedures. The
results summarized in Table 3 indicate that the present
procedure is better than all the earlier reported protocols
in terms of availability and cost of the catalyst.
d6 as a solvent. The chemical shifts (d) are reported in ppm
relative to TMS as an internal standard and J values are
given in Hz. 13C spectra were recorded at 75 MHz. Mass
spectra were recorded using a Hewlett Packard 5973 mass
spectrometer.
Table 3
Comparison between various methods and this work for the synthesis of
4aa.
Entry Catalyst
Time
Yield(%) cccc:cttcb Reference
4.2. Typical procedure for the synthesis of resorcinarenes
1
2
3
4
5
6
HCl
[Yb(H2O)9](OTf)3 48 h
11days 83
32:1
1.4:1
1:2c
[5c]
Iodine (20 mol%) was added to a solution of resorcinol
(1 mmol) and of an aldehyde (1 mmol) in 2 mL of absolute
ethanol. The solution was stirred at 78 8C. After a given
period of time, the solution was cooled and poured into
10 mL of an ice-cold saturated sodium thiosulfate aqueous
solution. The resulting precipitate was collected by
filtration and washed with water. The precipate was dried
at 90 8C and identified.
[8]
PTSA
BiCl3
Yb(TOS)3
I2
60 min
75 min 66
[6]
1:1.2
1:1.2
3:1
[9]
24 h
93
[10]
This work
75 min
a
Reaction conditions: benzaldehyde (1 mmol), resorcinol (1 mmol),
ethanol, catalyst.
b
Diastereomeric ratio from 1H NMR.
c
Solvent-free conditions.

F. Darvish, S. Khazraee / C. R. Chimie 17 (2014) 890–893
893
4.2.1. Spectroscopic data of 2,4,8,20-
6.41–6.43 (d, 8H, J = 4.71 Hz, ArH (C4 )), 8.35 (s, 4OH, ArOH
v
tetrabutylpentacyclo[19.3.1.1.1.1]octacosa
1(25),3,5,7(28),9,11,13(27),15,17,19(26),21,23-dodecaene-
4,6,10,12,16,18,22,24-octol (1a)
(C2 ), 8.39 (s, 4OH, ArOH (C2 )), 8.43 (s, 4OH, ArOH (C4 )),
v v v
8.66 (s, 4 OH, ArOH (C2 ), 8.83 s, 4OH, ArOH (C4 )).
v
v
1H NMR (DMSO-d6)
d
(ppm): 0.79 (t, 12H, J = 7.33 Hz,
4.2.6. Spectroscopic data of 2,4,8,20-tetra4-methoxy
phenylpentacyclo[19.3.1.1.1.1]
CH3), 1.08 (m, 8H, CH2CH3), 1.28 (quin, 8H, J = 6.84 Hz,
CH2CH2CH3), 2.01 (q, 8H, J = 6.73, ArCHCH2), 4.19 (t, 4H,
J = 7.69 Hz, methine) 6.13 (s, 4H, ArH, ortho to OH), 7.14 (s,
4H, ArH, meta to OH), 8.85 (s, 8H, 8OH). 13C NMR (DMSO-
octacosa1(25),3,5,7(28),9,11,13(27),15,17,19(26),21,23-
dodecaene 4,6,10,12,16,18,22,24-octol (6a/6b)
3.63 (s, 12 H CH3 (C2 )), 3.70 (s, 12 H CH3 (C4 )), 5.45 (s,
v
v
d6):
d
(ppm) = 14.1, 22.2, 30.1, 32.9, 33.6, 75.5, 102.3, 123.1,
4H, ArCH (C2 )), 5.55 (s, 2H, ArCH (C2 ) ortho to OH), 5.58 (s,
v v
125.0, 151.6. EI–MS, m/z = 712 (M+).
4H, ArCH (C4 )), 6.11 (s, 4H, ArH (C4 ), ortho to OH and 2H,
v v
ArH (C2 ), ortho to OH), 6.28 (s, 2H, ArH (C2 ) meta to OH),
v
v
4.2.2. Spectroscopic data of 2,4,8,20-
6.30 (s, 2H, ArH (C2 ), meta to OH and 4H, ArH (C4 )), 6.43–
v v
tetraoctylpentacyclo[19.3.1.1.1.1]octacosa
1(25),3,5,7(28),9,11,13(27),15,17,19(26),21,23-dodecaene-
4,6,10,12,16,18,22,24-octol (2a)
6.45 (d, 8H, J = 4.71 Hz, ArH (C4 )), 6.49–6.51 (d, 8H,
v
J = 4.8 Hz, ArH (C2 )), 6.53–6.55 (d, 8H, J = 4.8 Hz, ArH (C2 )),
v
v
6.59–6.61 (d, 8H, J = 4.71 Hz, ArH (C4 )), 8.41 (s, 4 OH, ArOH
v
1H NMR (DMSO-d6)
d
(ppm): 0.81 (t, 12H, J = 7.33 Hz,
(C2 ), 8.50 (s, 4 OH, ArOH (C2 ).
v
v
CH3), 1.20 (br, 48H, (CH2)6CH3), 1.96 (br, 8H, J = 6.84 Hz,
CHCH2), 4.23 (t, 4H, J = 7.69 Hz, methine) 6.14 (s, 4H, ArH,
ortho to OH), 7.08 (s, 4H, ArH, meta to OH), 8.85 (s, 8H,
References
8OH). 13C NMR (DMSO-d6):
d (ppm) = 14.0, 22.6, 29.2.2,
22.4, 27.6, 31.6, 31.9, 34.1, 75.5, 102.7, 123.2, 124.8, 151.8.
[1] (a) D.J. Cram, S. Karbach, H.E. Kim, C.B. Knobler, E.F. Maverick, J.L.
Ericson, R.C. Helgeson, J. Am. Chem. Soc. 110 (1988) 2229;
(b) Y. Aoyama, Y. Tanaka, H. Toi, H. Ogoshi, J. Am. Chem. Soc. 110 (1988)
634;
EI–MS, m/z = 938 (M+).
4.2.3. Spectroscopic data of 2,4,8,20-
(c) Y. Aoyama, Y. Tanaka, S. Sugahara, J. Am. Chem. Soc. 111 (1989)
5397;
(d) L.M. Tunstad, J.A. Tucker, E. Dalcanale, J. Weiser, J.A. Bryant, J.C.
Sherman, R.C. Helgeson, C.B. Knobler, D.J. Cram, J. Org. Chem. 54 (1989)
1305;
tetranonylpentacyclo[19.3.1.1.1.1]octacosa
1(25),3,5,7(28),9,11,13(27),15,17,19(26),21,23-dodecaene-
4,6,10,12,16,18,22,24-octol (3a)
1H NMR (DMSO-d6)
d
(ppm): 0.812 (t, 12H, J = 7.33 Hz,
(e) P. Timmerman, W. Verboom, D.N. Reinhoudt, Tetrahedron 52
(1996) 2663.
CH3), 1.20 (br, 56H, (CH2)7CH3), 1.96 (br, 8H, J = 6.84 Hz,
CHCH2), 4.21 (t, 8H, J = 7.69 Hz, methine) 6.15 (s, 4H, ArH,
ortho to OH), 7.06 (s, 4H, ArH, meta to OH), 8.87 (s, 8H,
8OH). 13C NMR (DMSO-d6):
d (ppm) =13.9, 14.1, 20.7, 22.1,
27.8, 28.7, 29.1, 29.2, 31.4, 59.8, 102.3, 122.8, 123.7, 151.7.
EI–MS, m/z = 993 (M+).
[2] O. Pietraszkiewicz, M. Pietraszkiewicz, Pol. J. Chem. 72 (1998) 2418.
[3] (a) K. Kobayashi, Y. Asakawa, Y. Kikuchi, H. Toi, Y. Aoyama, J. Am. Chem.
Soc. 115 (1993) 2648;
(b) L.R. MacGillivray, J.L. Atwood, J. Am. Chem. Soc. 119 (1997) 6931;
(c) K. Murayama, K. Aoki, Chem. Commun. (1998) 607;
(d) L.R. MacGillivray, P.R. Diamento, J.L. Reid, J.A. Ripmeester, Chem.
Commun. (2000) 359;
(e) A.J. Wright, S.E. Matthews, W.B. Fischer, P.B. Beer, Chem. Eur. J. 7
(2001) 3474.
[4] (a) S. Bonsignore, G. Cometti, E. Dalcanale, A. Du Vosel, Liq. Cryst. 8
(1990) 639;
4.2.4. Spectroscopic data of 2,4,8,20-
tetraphenylpentacyclo[19.3.1.1.1.1]octacosa
1(25),3,5,7(28),9,11,13(27),15,17,19(26),21,23-dodecaene-
4,6,10,12,16,18,22,24-octol (4a/4b)
(b) G. Cometti, E. Dalcanale, A. Du Vosel, A.M. Levelut, J. Chem. Soc.
Chem. Commun. (1990) 163;
(c) B.W. Purse, A. Shivanyuk, J. Rebek, Chem. Commun. (2002) 2612.
[5] (a) A.G.S. Ho¨gber, J. Org. Chem. 45 (1980) 4498;
(b) A.G.S. Ho¨gberg, J. Am. Chem. Soc. 102 (1980) 6046;
(c) L.M. Tunstad, J.A. Tucker, E. Dalcanale, J. Wesser, J.A. Brayant, J.C.
Sherman, J. Org. Chem. 54 (1989) 1305.
1H NMR (DMSO-d6)
d (ppm): 5.53(s, 4H, ArCH (C2 )),
v
5.55 (s, 2H, ArH (C2 ) ortho to OH), 5.62(s, 4H, ArCH (C4 )),
v
v
6.11 (s, 2H, ArH (C2 ) ortho to OH) 6.12 (s, 4H, ArH (C4 ),
v
v
ortho to OH), 6.33 (s, 4H, ArH (C4 ), meta to OH), 6.34 (s, 4H,
v
[6] B.A. Roberts, G.W.V. Cave, C.L. Raston, J.L. Scott, Green Chem. 3 (2001)
280.
ArH (C2 ), meta to OH), 6.58–6.60 (m, 8H, ArH (C2 )), 6.72–
v
v
[7] (a) A.D.M. Curtis, Tetrahedron Lett. 38 (1997) 4295;
(b) O.L. Pieroni, N.M. Rodriguez, B.M. Vuano, M.C. Cabaleiro, J. Chem.
Res. Synop. (1994) 188.
6.74 (d, 8H, ArH (C4 )), 6.83 (d, 12 H,, ArH (C2 )), 6.93 (d, 12
v
v
H,, ArH (C4 )), 8.44 (s, 4 OH, ArOH (C2 )), 8.55 (s, 4OH (C2
)
v
v
v
8OH (C4 ), ArOH)
[8] A.G.M. Barrett, D.C. Braddock, J.P. Henschke, E.R. Walker, J. Chem. Soc.
Perkin Trans. 1 (1999) 873.
v
[9] K.E. Peterson, R.C. Smith, R.S. Mohan, Tetrahedron Lett. 44 (2003) 7723.
[10] K. Deleersnyder, H. Mehdi, I.T. Horvath, K. Binnemans, T.N. Parac-Vogt,
Tetrahedron 63 (2007) 9063.
4.2.5. Spectroscopy data 2,4,8,20-tetra4-hydroxy
phenylpentacyclo[19.3.1.1.1.1]
[11] M. Hedidi, S.M. Hamdi, T. Mazari, B. Boutemeur, C. Rabia, F. Chemat, M.
Hamdi, Tetrahedron 62 (2006) 5652.
[12] H. Togo, S. Iida, Synlett 14 (2006) 2159.
[13] N. Deka, D.J. Kalita, R. Borah, J.C. Sarma, J. Org. Chem. 62 (1997) 1563.
[14] P.J. Phukan, Org. Chem. 69 (2004) 4005.
[15] S.J. Ji, S.Y. Wang, Y. Zhang, T.P. Loh, Tetrahedron Lett. 60 (2004) 2051.
[16] W. Roa, A.H.L. Tay, P.J. Goh, J.M.L. Choy, J.K. Ke, P.W.H. Chan, Tetrahe-
dron Lett. 49 (2008) 122.
octacosa1(25),3,5,7(28),9,11,13(27),15,17,19(26),21,23-
dodecaene 4,6,10,12,16,18,22,24-octol (5a/5b)
1H NMR (DMSO-d6)
d (ppm): 5.42 (s, 4H, ArCH (C2 )),
v
5.52 (s, 4H, ArCH (C4 )), 5.92 (s, 2H, ArH (C2 ) ortho to OH),
v
v
6.08 (s, 4H, ArH (C4 ), ortho to OH), 6.02 (s, 2H, ArH (C2
)
v
v
ortho to OH), 6.27 (s, 2H, ArH (C2 ), meta to OH), 6.31 (s, 4H,
v
[17] N.P. Selvam, P.T. Perumal, Tetrahedron 64 (2008) 2972.
ArH (C4 ), meta to OH), 6.33 (s, 2H, ArH (C2 ) meta to OH),
v
v