Zeolite-catalyzed simple synthesis of different heterocyclic rings, part 2

Article abstract of DOI:10.1002/hc.20036

A simple and environmentally friendly synthesis was developed for the preparation of 2-arylimidazoline derivatives and 2-arylbenzoxazole derivatives using a small pore size zeolite. The similar reaction was not applicable to the preparation of the sulfur-containing analogs cysteamine or 2-aminothiophenol, probably because of a disadvantageous reaction between the zeolite and the thio compound.

Full text of DOI:10.1002/hc.20036

Heteroatom Chemistry
Volume 15, Number 6, 2004
Zeolite-Catalyzed Simple Synthesis
of Different Heterocyclic Rings, Part 2
Adrienn Hegedu¨s, Ilona V´ıgh, and Zolta´n Hell
Department of Organic Chemical Technology, Budapest University of Technology and Economics,
H-1521 Budapest, Hungary
Received 20 May 2004
be recovered from the reaction mixture and reused
ABSTRACT: A simple and environmentally friendly
with good results.
synthesis was developed for the preparation of
During our work with a zeolite-type small pore
2-arylimidazoline derivatives and 2-arylbenzoxazole
size adsorbent, Ersorb-4 (E4), we investigated the
derivatives using a small pore size zeolite. The sim-
cyclization of benzoic acid derivatives with ꢀ-
ilar reaction was not applicable to the preparation
aminoalcohols. We obtained the appropriate oxazo-
of the sulfur-containing analogs cysteamine or 2-
line derivatives 3 in a simple reaction with good yield
aminothiophenol, probably because of a disadvanta-
[1] (Scheme 1).
geous reaction between the zeolite and the thio com-
ꢀ
C
pound. 2004 Wiley Periodicals, Inc. Heteroatom Chem
15:428–431, 2004; Published online in Wiley InterScience
RESULTS AND DISCUSSION
(www.interscience.wiley.com). DOI 10.1002/hc.20036
The 2-arylimidazoline derivatives are important
compounds because of their pharmaceutical activ-
ity [2]. The methods described for their preparation
INTRODUCTION
in the literature are based on the condensation of
ethylenediamine or its salt [3] with benzonitrile in
the presence of ZnCl2 and NH4Cl [4], P2S5 [5], with
ethyl benzoate [6], or with benzoic acid in the pres-
ence of Ph3P and Et3N [7]. Some of these methods
require reagents that are dangerous for the environ-
ment, or during the workup the safe disposal of the
reagents is tedious. Thus, the development of a sim-
ple new method seemed to be useful from the envi-
ronmental point of view, too.
We investigated whether our method devel-
oped for the preparation of oxazolines could be
adapted for the preparation of imidazolines. The
reaction of benzoic acid with ethylenediamine (4)
in the presence of E4 in boiling xylene resulted
in the formation of 2-phenylimidazoline (5a) in
73% yield. For changes of the reaction parameters
insignificant changes in the yield were observed.
Thus, when the reaction was conducted in boiling
toluene, instead of xylene, the yield decreased to 71%
The examination of the applicability of different
mineral-based reagents and catalysts in organic syn-
theses seems to be an important branch of the re-
search work in the preparative organic chemistry
even from the practical point of view. The applica-
tion of solid acids and bases (natural and modified
clay minerals, montmorillonites, zeolites, mixed ox-
ides, layered double hydroxides) is a significant aim
from the environmental point of view, too, since this
way the salt and acid–base contamination of indus-
trial waste waters appearing in the workup of the
reaction mixtures containing liquid acids and bases
could be avoided. In most cases these substances can
For Part one, see Ref. [1].
Correspondence to: Zolta´n Hell; e-mail: zhell@mail.bme.hu.
Contract grant sponsor: Hungarian Research Fund Programs.
Contract grant number: OTKA T 037757.
2004 Wiley Periodicals, Inc.
c
ꢀ
428

Zeolite-Catalyzed Simple Synthesis of Different Heterocyclic Rings, Part 2 429
TABLE 1 Reaction of Ethylenediamine with Aromatic Car-
boxylic Acids 1
R ꢁ
R ꢁꢁ
R ꢁꢁꢁ
Yield (%)
5a
5b
5c
5d
5e
5f
H
Cl
H
H
H
H
H
H
NO2
H
H
H
H
CH3
H
H
H
73
43
71
73
65
73
59
62
CH3
(CH3)3C
CH3O
H
SCHEME 1
5g
5h
OCOCH3
OH
while when the reaction time was reduced to 3 h,
66% of 5a were obtained. The catalyst can be eas-
ily recycled without significant loss of activity (73
and 69% in the first and second experiment, respec-
tively). The reaction of substituted benzoic acids
with ethylenediamine (Scheme 2) also yielded the
appropriate substituted 2-phenylimidazolines with
good yield (see Table 1). No significant substituent
effects were found, and no considerable amount of
by-products was observed.
H
EXPERIMENTAL
All compounds were characterized by 1H NMR spec-
troscopy. Spectra were made on Bruker AW-250
(250 MHz) spectrometer in CDCl3 using TMS as the
internal standard. The spectral and physical data of
the known compunds were identical with those re-
ported in the literature.
The commercial chemicals were purchased from
Merck-Hungary Ltd., except for E4, which is the
product of Erdo´´ke´mia-ker Ltd., Hungary.
Reaction of phenylacetic acid (6) with ethylene-
diamine gave the ꢁ-blocker tolazoline (7) with 69%
yield (Scheme 3).
For the appropriate thiazoline compounds, cys-
teamine (8) was reacted in boiling xylene with ben-
zoic acid, but the expected product was not obtained
even after longer heating. In the reaction under nor-
mal atmospheric conditions, cystamine-bis-amide
(9) was the product, while using Ar atmosphere we
isolated cysteamine amide (10) from the reaction
mixture (Scheme 4) In these reactions cysteamine
destroyed the structure of E4.
We investigated the preparation of the appro-
priate condensed heterocycles, too. Replacing 2-
aminoethanol with o-aminophenol (11) under the
same conditions, the benzoxazole derivatives (12)
were obtained (Scheme 5) with good yield (see Ta-
ble 2), except in case of salicylic acid, where no
product could be isolated. Surprisingly o-phenylene-
diamine (13) and o-aminothiophenol (15) gave only
the monoamides 14 and 16, respectively (Schemes
6 and 7). In the first case the lack of the dehydra-
tion might be explained with solubility problems;
the amide precipitated from the reaction mixture.
In the latter case the thiophenol, similarly to the cys-
teamine, destroyed the zeolite.
Pretreatment of the Catalyst
Before the experiments, a sample of E4 was pow-
dered and heated at 120◦C for 2 h.
Typical Procedure for the Preparation
of 2-Arylimidazolines (5)
A mixture of 1 (5 mmol), ethylenediamine (4)
(5 mmol, 0.3 g, 0.31 mL), and 0.8 g E4 was heated
at 130◦C for 5 h. The solid was then filtered out and
washed with acetone; the filtrate was evaporated and
the residue was characterized.
2-Phenylimidazoline (5a). White solid, mp 149–
151◦C (lit. 147–149◦C [8]). H NMR (CDCI3 ppm):
δ 3.7 (t, 4H, CH2 4.8 (t, 1H, NH), 7.2–7.6 (m, 3H,
Ar), 7.8 (m, 2H, Ar). Anal. Found: C, 73.79; H, 6.81;
1
TABLE 2 Reaction of o-Aminophenol with Aromatic Car-
boxylic Acids 1
R ꢁ
R ꢁꢁ
R ꢁꢁꢁ
Yield (%)
12a
12b
12c
12d
12e
12f
H
Cl
H
H
H
H
H
H
H
H
H
CH3
H
OH
73
64
89
77
75
—
(CH3)3C
H
CH3
H
SCHEME 2

430 Hegedu¨s, V´ıgh, and Hell
SCHEME 3
SCHEME 5
N, 19.28%. Calcd for (C9H10N2): C, 73.94; H, 6.89;
N, 19.16%.
C, 77.01; H, 9.08; N, 13.92%. Calcd for (C13H18N2):
C, 77.18; H, 8.97; N, 13.85%.
2-(4-Chlorophenyl)-imidazoline (5b). Yellowish
1
solid, mp 190–193◦C (lit. 186–187◦C [9]). H NMR
2-(4-Methoxy-3-nitrophenyl)-imidazoline
(5f).
Yellow solid, mp 194–196◦C. 1H NMR (CDCl3, ppm):
δ 3.5 (t, 4H, CH2), 3.9 (s, 3H, CH3), 4.7 (t, 1H, NH),
7.2 (d, 1H, Ar), 7.9 (d, 1H, Ar), 8.3 (s, 1H, Ar).
Anal. Found: C, 54.11; H, 5.19; N, 19.06%. Calcd for
(C10H11N3O3): C, 54.30; H, 5.01; N, 18.99%.
(CDCl3, ppm): δ 3.6 (t, 4H, CH2), 4.8 (t, 1H, NH),
7.2–7.7 (m, 4H, Ar). Anal. Found: C, 59.93; H, 5.21;
N, 15.39%. Calcd for (C9H9N2Cl): C, 59.84; H, 5.02;
N, 15.51%.
2-(2-Methylphenyl)-imidazoline (5c). Yellowish
1
solid, mp 115◦C (lit. 85–86◦C [9]). H NMR (CDCl3,
2-(2-Acetoxyphenyl)-imidazoline (5g). Oil. 1H
NMR (CDCl3, ppm): δ 2.8 (s, 3H, CH3), 3.6 (t, 4H,
CH2), 4.7 (t, 1H, NH), 7.3 (dd, 2H, Ar), 7.8 (d, 1H,
Ar), 8.1 (d, 1H, Ar). Anal. Found: C, 64.81; H, 5.99;
N, 13.58%. Calcd for (C11H12N2O2): C, 64.69; H, 5.92;
N, 13.72%.
ppm): δ 2.3 (s, 3H, CH3), 3.6 (t, 4H, CH2), 4.7 (t, 1H,
NH), 7.0–7.4 (m, 3H, Ar), 7.7 (d, 1H, Ar). Anal. Found:
C, 75.11; H, 7.45; N, 17.51%. Calcd for (C10H12N2): C,
74.97; H, 7.55; N, 17.48%.
2-(4-Methylphenyl)-imidazoline (5d). Yellowish
1
solid, mp 179–181◦C (lit. 178–179◦C [9]). H NMR
2-(2-Hydroxyphenyl)-imidazoline (5h). Yellow-
ish solid, mp 211–212◦C (lit. 214–216◦C [10]). 1H
NMR (CDCl3, ppm): δ 3.7 (dt, 4H, CH2), 4.8 (t, 1H,
NH), 5.4 (s, 1H, OH), 7.1–7.7 (m, 4H, Ar). Anal.
Found: C, 66.81; H, 6.09; N, 17.19%. Calcd for
(C9H10N2O): C, 66.65; H, 6.21; N, 17.27%.
(CDCl3, ppm): δ 2.2 (s, 3H, CH3), 3.7 (t, 4H, CH2),
4.8 (t, 1H, NH), 7.0–7.3 (m, 2H, Ar), 7.8 (dd, 2H,Ar).
Anal. Found: C, 74.82; H, 7.67; N, 17.39%. Calcd for
(C10H12N2): C, 74.97; H, 7.55; N, 17.48%.
2-(4-tert-Butylphenyl)-imidazoline (5e). White
1
solid, mp 191–193◦C. H NMR (CDCl3, ppm): δ 1.3
2-Benzylimidazoline (7). 1H NMR (CDCl3, ppm):
δ 3.6 (m, 6H, CH2), 4.4 (t, 1H, NH), 7.4 (m, 5H, Ar).
Anal. Found: C, 72.81; H, 8.29; N, 18.99%. Calcd for
(C9H12N2): C, 72.94; H, 8.16; N, 18.90%.
(s, 9H, CH3), 3.6 (dt, 4H, CH2), 4.8 (t, 1H, NH),
7.1–7.4 (m, 2H, Ar), 7.8 (dd, 2H, Ar). Anal. Found:
Typical Procedure for the Preparation
of 2-Arylbenzoxazole (12)
A mixture of 1 (5 mmol), o-aminophenol (11)
(5 mmol, 0.55 g) and 0.8 g E4 in xylene was heated
at 130◦C for 5 h. The solid was then filtered out and
washed with acetone; the filtrate was evaporated and
the residue was characterized.
SCHEME 4
SCHEME 6

Zeolite-Catalyzed Simple Synthesis of Different Heterocyclic Rings, Part 2 431
N,Nꢁ-(3,4-Dithia-hexanedityl)-bis-benzamide (9).
Yellow solid, mp 130◦C (lit. 132–133◦C [16]).
N-(2-Mercapto-ethyl)-benzamide (10). Yellow
solid, mp 72◦C (lit. 70–71◦C [17]).
SCHEME 7
N-(2-Aminophenyl)-benzamide (14). Yellowish
solid, mp 148–150◦C (lit. 150–152◦C [18]).
2-Phenylbenzoxazole (12a). Yellowish solid, mp
N-(2-Mercapto-phenyl)-benzamide (15). Yellow
solid, mp 107–108◦C (lit. 109–110◦C [19]).
107◦C (lit. 109–110◦C [11]). 1H NMR (CDCl3, ppm): δ
7.3–7.6 (m, 5H, Ar), 7.8 (dd, 2H, Ar), 8.1 (m, 2H, Ar).
Anal. Found: C, 79.83; H, 4.79; N, 7.25%. Calcd for
(C13H9NO): C, 79.98; H, 4.65; N, 7.17%.
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2-(4-Chlorophenyl)-benzoxazole (12b). Yellow-
ish solid, mp 152◦C (lit. 151–152◦C [12]). 1H
NMR (CDCl3, ppm): δ 7.4–7.6 (m, 4H, Ar), 7.8–8.0
(m, 4H, Ar). Anal. Found: C, 68.07; H, 3.59; N,
6.01%. Calcd for (C13H8NOCl): C, 67.99; H, 3.51;
N, 6.10%.
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2-(4-tert-Butylphenyl)-benzoxazole (12c). Yel-
1
lowish solid, mp 105◦C (lit. 105◦C [13]). H NMR
(CDCl3, ppm): δ 1.2 (s, 9H, CH3), 7.2–7.7 (m, 4H,
Ar), 7.9 (m, 4H, Ar). Anal. Found: C, 81.10; H, 6.89;
N, 5.63%. Calcd for (C17H17NO): C, 81.24; H, 6.82;
N, 5.57%.
2-(2-Methylphenyl)-benzoxazole (12d). Yellow-
1
ish solid, mp 71◦C (lit. 69◦C [14]). H NMR (CDCl3,
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ppm): δ 2.4 (s, 3H, CH3), 7.3–7.5 (m, 5H, Ar), 7.8–
8.0 (m, 3H, Ar). Anal. Found: C, 80.19; H, 5.37;
N, 6.87%. Calcd for (C14H11NO): C, 80.36; H, 5.30;
N, 6.69%.
2-(4-Methylphenyl)-benzoxazole (12e). Yellow-
1
ish solid, mp 117◦C (lit. 116–117◦C [15]). H NMR
(CDCl3, ppm): δ 2.2 (s, 3H, CH3), 7.2–7.7 (m, 4H,
Ar), 8.0 (m, 4H, Ar). Anal. Found: C, 80.17; H, 5.42;
N,6.75%. Calcd for (C14H11NO): C, 80.36; H, 5.30; N,
6.69%.