Synthesis of 25,26,27-tris(Ethoxycarbonylmethoxy)-28-(substituted oxy-carbonylmethoxy) calix-4-arene: First example of calix-imidazole/benzimidazole analog

Article abstract of DOI:10.1081/SCC-120015765

Synthesis of calix-imidazole/benzimidazole analog i.e., 25,26, 27-tris-(ethoxycarbonylmethoxy)-28-({2′-phenylcarbamoyl} benzimidazolyloxycarbonylmethoxy) calix-4-arene. 6_a, 25,26,27-tris-(ethoxycarbonylmethoxy)-28-((2″-phenylcarbamoyl} 4′,5′-di

Full text of DOI:10.1081/SCC-120015765

Synthetic Communications
An International Journal for Rapid Communication of Synthetic Organic
Chemistry
ISSN: 0039-7911 (Print) 1532-2432 (Online) Journal homepage: http://www.tandfonline.com/loi/lsyc20
Synthesis of 25,26,27- tris
(Ethoxycarbonylmethoxy)-28-(substituted Oxy-
carbonylmethoxy) Calix-4-arene: First Example of
Calix-imidazole/Benzimidazole Analog
Pratibha Sharma , Ashok Kumar & Anupam Mandloi
To cite this article: Pratibha Sharma , Ashok Kumar & Anupam Mandloi (2003) Synthesis of
25,26,27- tris (Ethoxycarbonylmethoxy)-28-(substituted Oxy-carbonylmethoxy) Calix-4-arene:
First Example of Calix-imidazole/Benzimidazole Analog, Synthetic Communications, 33:3,
373-380, DOI: 10.1081/SCC-120015765
To link to this article: http://dx.doi.org/10.1081/SCC-120015765
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SYNTHETIC COMMUNICATIONSÕ
Vol. 33, No. 3, pp. 373–380, 2003
Synthesis of 25,26,27-
tris(Ethoxycarbonylmethoxy)-28-(substituted
Oxy-carbonylmethoxy) Calix-4-arene:
First Example of Calix-imidazole/
Benzimidazole Analog
*
Pratibha Sharma, Ashok Kumar, and Anupam Mandloi
Institute ofChemical Sciences, Devi Ahilya University,
Indore, M.P., India
ABSTRACT
Synthesis ofcalix-imidazole/benzimidazole analog i.e., 25,26,
27-tris-(ethoxycarbonylmethoxy)-28-({20-phenylcarbamoyl} benzimi-
dazolyloxycarbonylmethoxy) calix-4-arene. 6a, 25,26,27-tris- (ethoxy-
carbonylmethoxy)-28-({200-phenylcarbamoyl} 40,50 -dihydroimidazo-
lyloxy-carbonylmethoxy) calix-4-arene. 6b and 25,26,27-tris-
*Correspondence: Pratibha Sharma, Institute ofChemical Sciences, Devi Ahilya
University, Indore 452 017, M.P., India.
373
DOI: 10.1081/SCC-120015765
Copyright & 2003 by Marcel Dekker, Inc.
0039-7911 (Print); 1532-2432 (Online)
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374Sharma, Kumar, and Mandloi
(ethoxycarbony-methoxy) calix-4-arene 6c have been described.
Structure elucidation explains the interaction ofsubstituted imida-
zole/benzimidazole (1a–c) with calix-4-arene system. Purity ofall the
synthesized products was ascertained on the basis oftheir column
chromatographic resolution on silica gel using chloroform–
ethylacetate (7:3, v/v) as eluent and recrystallization from a mixture
ofchloroform–methanol (1:1, v/v).
INTRODUCTION
Calixarenes are a class ofversatile molecular hosts with growing
[1,2]
applications in the field ofsupramolecular chemistry.
They are
recently rediscovered phenolic macrocyclic compounds which have
immense potential for obtaining molecular receptor[1–5] that are not
only important for recognition of small ions and organic molecules,[6–13]
but are also useful for the design of new drug delivery systems, chro-
mogenic indicators and chemical sensors.[14–15] It has been observed that
calix(n)arene can form complexes in the solid state as well as in the
solution phase.[16–19] The aggregation ofcalix(n)arene to yield molecular
voids and micelle like structures in solution has not been investigated
in detail though some water soluble calixarene sulphonates have
been examined earlier by conductometry.[20] Investigations into the
aggregation ofcalix(n)arenes in non-aqueous solutions have been
reported.[21–22]
In this communication we report herein the synthesis ofthe calix-
imidazole/benzimidazole analog, 25,26,27-tris(ethoxycarbonylmethoxy)-
28-(substituted oxycarbonylmethoxy) calix-4-arene. 6a–c
Substituted imidazole/benzimidazole compound 1a–c have been
synthesized by adding o-phenylenediamine/ethylenediamine in the pre-
[23]
sence ofsulphur to their respective chloroacetyl derivatives
(Sch. 1).
5,11,17,23-tetra-butyl-25,26,27,28-tetrahydroxycalix-4-arene(2) was syn-
thesized by the condensation ofofrmaldehyde with p-(t-butyl)phenol
[1]
in the presence ofsodium hydroxide by the Gutsche’s method.
This (2) was then workup[24] to form 25,26,27-tris(ethoxycarbonyl-
methoxy)-28-(carboxy-methoxy) calix-4-arene (5) (Sch. 2). Compound
(5) was condensed with substituted imidazole/benzimidazole 1a–c
in the presence ofNaH/THF to give the desired calix-imidazole/
benzimidazole 6a–c
.

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Calix-imidazole/Benzimidazole Analog
375
Scheme 1.
Scheme 2.

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376
Sharma, Kumar, and Mandloi
Scheme 3.
EXPERIMENTAL SECTION
General Reaction Procedure
2-(40-Chlorophenylcarbamoyl) benzimidazole (1a): Chloroacetylchlor-
ide (5.6 mL, 0.05 mol) was added to a stirred solution of p-chloroaniline
(I) (0.05 mol) in glacial acetic acid (40.0 mL) at 10ꢀC. The temperature
slowly rose to 28–30ꢀC. This was stirred for 25–30 min. A 60% solution
ofsodium acetate (50.0 mL) was then added and the mixture stirred of r
20 min. The precipitate formed was filtered, washed with water and dried
at 80ꢀC and recrystallized from a mixture of dimethylformamide and
ethanol 3:7 (v/v), in order to obtain N-chloroacetylated derivative (II).
Now, o-phenylenediamine (2.6 g, 0.02 mol) was added portionwise to a
mixture ofII (4.28 g, 0.02 mol) in toluene (60.0 mL) and sulphur (1.28 g,
0.03 mol) at 100ꢀC during 2 h. The reaction mixture was then heated at
100ꢀC under stirring for 4 h and filtered hot. The insoluble solid was
discarded. The filtrate was concentrated to 1/5th volume and cooled to

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Calix-imidazole/Benzimidazole Analog
377
0ꢀC. A gummy precipitate was formed. This was decanted and recrystal-
lized from methanol to give a crystalline precipitate of 1a.
1a: M.p. 230ꢀC, yield 72% (Found: C, 61.62; H, 3.60; N, 15.40. Calc.
for C14H10N3OCl: C, 61.87; H, 3.68; N, 15.46); IR (nujol) cmÀ1: 1600
(aromatic), 1770 (C¼O), 3313 (ÀNH); NMR (CDCl3) ꢀ: 2.5 (4H, CH2
proton), 4.0 (2H, ArNHR proton).
2-(40-Chlorophenylcarbamoyl)-4,5-dihydroimidazole: Chloroacetylchlo-
ride (5.6 mL, 0.05 mol) was added to a stirred solution of p-chloroaniline
(I) (0.05 mol) in glacial acetic acid (40.0 mL) at 10ꢀC. The temperature
slowly rose to 28–30ꢀC. This was stirred for 25–30 min. A 60% solution
ofsodium acetate (50.0 mL) was then added and the mixture stirred ofr
20 min. The precipitate formed was filtered, washed with water and dried
for 20 min. The precipitate formed was filtered, washed with water and
dried at 80ꢀC and recrystallized from a mixture of dimethylform-
amide and ethanol 3:7 (v/v), in order to obtained N-chloroacetylated
derivative (II).
Now, ethylenediamine (0.02 mol) was added portionwise to a mixture
ofII (4.28 g, 0.02 mol) in toluene (60.0 mL) and sulphur (1.28 g, 0.03 mol)
at 100ꢀC during 2 h. The reaction mixture was then heated at 100ꢀC
under stirring for 4 h and filtered hot. The insoluble solid was discarded.
The filtrate was concentrated to 1/5th volume and cooled to 0ꢀC. A
gummy precipitate was formed. This was decanted and recrystallized
from methanol to give a crystalline precipitate of 1b: m.p. 228ꢀC, yield
73% (Found: C, 54.11; H, 3.57; N, 18.91. Calc. for C12H8N3OCl: C,
54.17; H, 3.61; N, 18.96); IR (nujol) cmÀ1: 1600 (aromatic), 17.68
(–C¼O), 3312 (–NH), NMR (CDCl3) ꢀ: 2.4 (4H, CH2 proton), 3.9 (2H,
ArNHR proton).
2-(40-Chlorophenylaminocarbamoyl)-4,5-dihydroimidazole: Scheme 1:
Chloroacetylchloride (5.6 mL, 0.05 mol) was added to a stirred solution
of p-chlorophenylhydrazine[25] (IIb) (0.05 mol) in glacial acetic acid
(40.0 mL) at 10ꢀC. The temperature slowly rose to 28–30ꢀC. This was
stirred for 25–30 min. A 60% solution of sodium acetate (50.0 mL) was
filtered, washed with water and dried at 80ꢀC and recrystallized from a
mixture ofdimethylformamide and ethanol 3:7 (v/v) in order to obtained
N-chloroacetylated derivative (IIb).
Now, ethylenediamine (0.02 mol) was added protionwise to a mixture
ofII (0.02 mol) in toluene (60.0 mL) and sulphur (1.28 g, 0.03 mol) at
b
100ꢀC during 2 h. The reaction mixture was then heated at 100ꢀC under
stirring for 4 h and filtered hot. The insoluble solid was discarded. The
filtrate was concentrated to 1/5th volume and cooled to 0ꢀC. A gummy
precipitate was formed. This was decanted and recrystallized from

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378
Sharma, Kumar, and Mandloi
methanol to give a crystalline precipitate of1 : m.p. 237ꢀC, yield 77%
c
(Found: C, 54.37; H, 4.10; N, 25.40. Calc. for C10H9N4OCl: C, 54.42; H,
4.08; N, 25.39); IR (nujol) cmÀ1: 1590 (atomatic), 1765 (–C¼O), 3312
(–NH); NMR (CDCl3) ꢀ: 2.4 (4H, CH2 proton), 3.9 (2H, ArNHR
proton).
25,26,27-tris(Ethoxycarbonylmethoxy)-28-({20-phenylcarbamoyl}benz
-
imidazolyloxy carbonylmethoxy) calix-4-arene (6a): Scheme 3: To a mix-
0
ture of2-(4 -chlorophenylcarbamoyl) benzimidazole (1a) (1.02 mmol) and
sodium hydride (0.126 g, 1.0 mmol) in dry tetrahydrofuran (20.0 mL), 5
(0.81 g, 1.13 mmol) was added and stirred for 24 h. Removal of solvent
under reduced pressure gave a residue which was dissolved in chloroform
dried (sodium sulphate) and evaporated to yield 6a. It was purified by
column chromatography over silica gel 200 g using chloroform–ethylace-
tate (1:1) as eluent and recrystallized (chloroform–methanol) to give white
needles 6a: m.p. 228ꢀC, yield 42% (Found: C, 68.61; H, 5.25; N, 4.30. Calc.
for C55H51N3O13: C, 68.67; H, 5.30; N, 4.37); IR (Nujol) cmÀ1: 1715
1
(–C¼O); H NMR (CDCl3) ꢀ: 7.25–6.60 (m, 15H, ArH), 6.02 (S, 1H, H–
C¼C).
25,26,27-tris(Ethoxycarbonylmethoxy)-28-({20-phenylcarbamoyl}-40,50-
dihydraimidazolyloxycarbonylmethoxy) calix-4-arene (6b): Scheme 3:
To
a
mixture of2-(4 0-chlorophenylcarbamoyl)-4,5-dihydroimidazole
(1a) (1.02 mmol) and sodium hydride (0.126 g, 1.0 mmol) in dry tetrahy-
drofuran (20.0 mL) 5 (0.81 g, 1.13 mmol) was added and stirred for 24 h.
Removal ofsolvent under reduced pressure gave a residue which was
dissolved in chloroform dried (sodium sulphate) and evaporated to
yield 6b. It was purified by column chromatography over silica gel
200 g using chloroform–ethylacetate (1:1) as eluent and recrystallized
(chloroform–methanol) to give white needles 6b: m.p. 226ꢀC, yield 45%
(Found: C, 67.12; H, 5.28; N, 4.56. Calc. for C51H49N3O13: C, 67.17; H,
5.37; N, 4.61); IR (nujol) cmÀ1: 1710 (–C¼O); 1H NMR (CDCl3) ꢀ:
7.35–6.80 (m, 12H, ArH), 6.0 (S, IH, H–C¼C).
25,26,27-tris(Ethoxycarbonylmethoxy)-28-({20-phenylaminocarbamoyl}-
40,50-dihydraimidazolyloxycarbonylmethoxy) calix-4-arene (6c): Scheme 3:
To a mixture of2-(4 0-chlorophenylaminocarbamoyl)-4,5-dihydroimid-
azole (1c) (1.02 mmol) and sodium hydride (0.126 g, 1.0 mmol) in dry
tetrahydrofuran (20.0 mL), 5 (0.81 g, 1.13 mmol) was added and stirred
for 24 h. Removal of solvent under reduced pressure gave a residue which
was dissolved in chloroform dried (sodium sulphate) and evaporated to
yield 6c. It was purified by column chromatography over silica gel 200 g
using chloroform–ethylacetate (1:1) as eluent and recrystallized (chloro-
form–methanol) to give white needless 6c: m.p. 227ꢀC, yield 44%

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Calix-imidazole/Benzimidazole Analog
379
(Found: C, 67.21; H, 5.42; N, 6.18. Calc. for C51H50N4O13: C, 67.25;
H, 5.49; N, 6.15); IR (nujol) cmÀ1: 1712 (–C¼O); 1H NMR (CDCl3)
ꢀ: 7.33–6.90 (m, 12H, ArH), 6.0 (S, 1H, H–C¼C).
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Received in the Netherlands October 31, 2001