Alumina-ammonium acetate as an efficient reagent for the one-pot synthesis of cis-2,4,5-triarylimidazolines from aromatic aldehydes

Article abstract of DOI:10.3987/COM-04-10203

A simple, efficient, and new method has been developed for the synthesis of 2,4,5-triarylimidazolines from aldehydes through a one-pot reaction of aldehydes in the presence of alumina-ammonium acetate under solvent-free conditions using microwave irradiation. This method is easy, rapid, one-pot and good to high-yielding reaction for the synthesis of 2,4,5-triarylimidazolines.

Full text of DOI:10.3987/COM-04-10203

HETEROCYCLES, Vol. 65, No. 2, 2005
353
HETEROCYCLES, Vol. 65, No. 2, 2005, pp. 353 - 357
Received, 17th August, 2004, Accepted, 8th December, 2004, Published online, 10th December, 2004
ALUMINA-AMMONIUM ACETATE AS AN
EFFICIENT REAGENT FOR THE ONE-POT
SYNTHESIS OF CIS-2,4,5-TRIARYLIMIDAZOLINES
FROM AROMATIC ALDEHYDES
Babak Kaboudin* and Fariba Saadati
Department of Chemistry, Institute for Advanced Studies in Basic Sciences
(IASBS), Gava Zang, Zanjan 45195-159, Iran
Fax: (+98) 241 4249023
E-mail: kaboudin@iasbs.ac.ir
Abstract – A simple, efficient, and new method has been developed for the
synthesis of 2,4,5-triarylimidazolines from aldehydes through a one-pot reaction
of aldehydes in the presence of alumina-ammonium acetate under solvent–free
conditions using microwave irradiation. This method is easy, rapid, one-pot and
good to high-yielding reaction for the synthesis of 2,4,5-triarylimidazolines.
2,4,5-Triarylimidazolines are good precursors for the synthesis of imidazoles and diarylethylenediamines
that can be used as chiral ligands in asymmetric synthesis.1 The most important method for the synthesis
of 2,4,5-triarylimidazolines is the reaction of aromatic aldehydes with ammonia to give the diimine
compounds, N,N’-bis(arylmethylidene)arylmethanediamines, and followed by heating with strong base to
form triarylimidazolines (Scheme 1).2 Recently, new methods have been reported for the synthesis of
triarylimidazolines using of HMDS in the presence of Lewis acids such as ZnCl2 3 or without any catalyst
under solvent-free conditions using microwave irradiation.4 The application of microwave energy to
accelerate organic reactions is of increasing interest and offers several advantages over conventional
techniques.5 As part of our efforts to explore the utility of mixture of alumina with ammonium acetate for
the synthesis of organic compounds under microwave irradation,6 we report a new method for the
preparation of cis-triarylimidazolines from aldehydes in the presence of a mixture of alumina with
ammonium acetate under solvent-free conditions using microwave irradiation. (Scheme 1, Table 1).
The reaction of benzaldehyde (1a), chosen as a model compound, was studied in the presence of a
mixture of alumina with several ammonium salts. Initially, we carried out the reaction of benzaldehyde in

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HETEROCYCLES, Vol. 65, No. 2, 2005
a mixture of alumina with ammonium acetate under microwave irradiation to afford the corresponding
cis-2,4,5-triphenylimidazoline in 80% yield after 2 min. When this reaction was carried out in methanol
for 3 h it afforded the corresponding cis-2,4,5-triphenylimidazoline in 10% yield. Ammonium formate
(HCO2NH4) was not as effective as ammonium acetate and gave the required product in 35% yield under
microwave irradiation. Other ammonium salts (NH4Cl, NH4Br, NH4PF6, NH4I and NH4NO3) were not
effective and did not give such product.
These results prompted us to extend this process to other aromatic aldehydes. Interestingly, aromatic
aldehydes reacted smoothly in a mixture of alumina with ammonium acetate under microwave irradiation
to produce the corresponding cis-triarylimidazolines in good to excellent yields (Table 1 and Scheme 2).
As shown in Table 1, substituted benzaldehydes in the presence of a mixture of alumina with ammonium
acetate, afforded the desired products in good to high yields (2a-2h). Naphthalenecarbaldehydes also
reacted in the presence of a mixture of alumina with ammonium acetate under microwave irradiation to
give the desired compounds in good yields (2i, 2j). The reactions were clean with no tar formation and
can be carried out in a one-step operation of aldehydes with ammonium acetate for the synthesis of
cis-triarylimidazolines.
Ar
Al2O3/ NH4OAc
MW/2-5 min
NH
Ar
N
ArCHO
Ar
2
1
Scheme 2
Table 1. One-pot Synthesis of cis-triarylimidazolines from aldehydes in the presence of
alumina-supported ammonium acetate under microwave irradiation.
Product
Ar-
Time
Yield
(%)
Product
Ar-
Time
Yield
(%)
53(83)
75
2
a
b
c
1
(min)
2
f
1
(min)
C6H5-4a
2
3
2
4
80(85)
79(82)
78(83)
70(86)
72
p-BrC6H4-4a
m-O2NC6H4-
o-ClC6H4-
α-Naphthyl
β-Naphthyl
3
2
4
5
4
p-MeC6H4-4a
p-ClC6H4-4a
p-MeOC6H4-4a
g
h
i
56
d
e
68
p-(CH3)2CHC6H4- 5
j
76

HETEROCYCLES, Vol. 65, No. 2, 2005
355
In summary, simple work-up, low use of solvents, fast reaction rates, mild reaction conditions, good yields
and the relatively clean reactions with no tar formation make this method an attractive and a useful
contribution to present methodologies.
ACKNOWLEDGMENT
The Institute for Advanced Studies in Basic Sciences (IASBS) is thanked for supporting this work.
EXPERIMENTAL
General: All chemicals were commercial products and distilled or recrystallized before use. All melting
points were obtained by a Buchi 510 and are uncorrected. A commercially available pulse microwave at
2450 MHz (900 W) was used in all experiments. IR spectra were determined using a FT-IR Brucker-Vector
22. NMR spectra were taken with a DMX-500 Bruker Avance instrument with the chemical shifts being
reported as δ ppm and couplings expressed in Hertz. Silica gel column chromatography was carried out
with Silica gel 100 (Merck No. 10184). Merck Silica-gel 60 F254 plates (No. 5744) were used for the
preparative TLC. Aluminiumoxide 90 active acidic (activity stage I) was used for the reactions (Merck No.
1078).
Preparation of cis-Triarylimidazolines:
General Procedure: This solvent-free reaction is operationally simple. 10 Mmol of the reagent was
prepared by the combination of ammonium acetate (0.77 g,10 mmol, finely ground) and alumina (Al2O3,
acidic, 2.5 g) in a mortar and pestle by grinding them together until a fine, homogeneous, powder was
obtained (5-10 min). The aldehyde (9 mmol) was added to this reagent and the mixture was irradiated in a
microwave for 2-5 min using 600 W. (A kitchen-type microwave instrument was used in all experiments).
The mixture was then washed with 200 mL of EtOAc. The solvent was evaporated. Chromatography of the
residue through a plug of silica gel with EtOAc/n-hexane (1:9 to 5:5) and evaporation of the solvent under
reduced pressure gave the pure products in 53-90% yields. All products gave satisfactory spectral data in
accord with the assigned structures and literature reports. 4a For new compounds spectral data are reported
as following:
cis-2,4,5-Tris(p-isopropylphenyl)imidazoline (2e):
1
This imidazoline was prepared in the general way and had mp 222-224°C (ethanol). H-NMR
(CDCl3/TMS-500 MHz): 1.05 (6H, d, J=6.8 Hz), 1.22 (6H, d, J=6.8 Hz), 1.26 (6H, d, J=6.8 Hz), 2.66 (2H,
sep, J=6.8 Hz), 2.89 (1H, sep, J=6.9 Hz), 4.90 (2H, s), 6.57 (4H, d, J=7.9 Hz), 6.78 (4H, d, J=7.9 Hz), 7.46
13
(2H, d, J=8.1 Hz) 8.52 (2H, d, J=8.1 Hz), 10.93 (1H, br); C-NMR (CDCl3/TMS-125.7 MHz): 23.53,
23.66, 23.73, 33.52, 34.03, 65.70, 120.75, 125.56, 127.03, 129.82, 130.66, 132.18, 148.23, 152.82, 165.06;

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HETEROCYCLES, Vol. 65, No. 2, 2005
IR (KBr): 3220 (-NH), 1620 (C=N) cm-1; MS m/z: 424 (M+). Anal. Calcd for C30H36N2. C, 84.90; H, 8.49;
N, 6.60. Found: C, 84.77; H, 8.41; N, 6.80.
cis-2,4,5-Tris(m-nitrophenyl)imidazoline (2g):
1
This imidazoline was prepared in the general way and had mp 130-142° C (ethanol). H-NMR, δH
(CD3SOCD3, TMS): 5.82 (s, 2H), 7.32-7.45 (m, 4H), 7.81-7.89 (m, 5H), 8.44-8.53 (m, 3H), 8.89 (s, 1H);
13C-NMR, δc (CDCl3, TMS): 61.04, 121.99, 122.29, 122.56, 126.07, 129.61, 130.75, 131.46, 134.20,
142.25, 147.50, 148.34, 162.97; IR (KBr): 3379 (-NH), 1610 (C=N) cm-1; MS m/z: 433 (M+). Anal. Calcd
for C21H15N5O6. C, 58.20; H, 3.46; N, 16.16. Found: C, 58.45; H, 3.66; N, 16.32.
cis-2,4,5-Tris(o-chlorophenyl)imidazoline (2h) :
1
This imidazoline was prepared in the general way and had mp 132-134° C (ethanol). H-NMR, δH
(CD3SOCD3, TMS): 6.04 (s, 2H), 6.94-7.01 (m, 4H), 7.09-7.26 (m, 4H), 7.36-7.48 (m, 3H), 7.97 (d, 1H,
J=7.5 Hz) ; 13C-NMR, δc (CDCl3, TMS): 61.79, 123.26, 127.22, 128.26, 129.61, 130.41, 130.66, 130.98,
131.93, 132.03, 132.20, 132.81, 135.15, 164.88; IR (KBr): 3200 (-NH), 1610 (C=N) cm-1; MS m/z: 400
(M+). Anal. Calcd for C21H15 N2Cl3. C, 62.76; H, 3.74; N, 6.97. Found: C, 62.96; H, 3.98; N, 6.97.
cis-2,4,5-Tris(α-naphthyl)imidazoline (2i):
1
This imidazoline was prepared in the general way and had mp 240-242° C (ethanol). H-NMR
(CD3SOCD3/TMS-500 MHz): 6.39 (2H, s), 6.98-7.01 (3H, m), 7.09-7.27 (6H, m), 7.36 (2H, d, J=8.1 Hz),
7.46-7.59 (6H, m), 7.76 (2H, d, J=8.2 Hz), 7.92-7.97 (3H, m), 8.81 (1H, m); 13C-NMR
(CD3SOCD3/TMS-125.7 MHz): 66.6, 125.3, 125.6, 126.0 127.1, 127.6, 127.7, 127.8, 128.1, 128.3, 129.0,
132.7, 132.8, 134.4, 138.4, 164.25; IR (KBr): 3140 (-NH), 1590 (C=N) cm-1; MS m/z: 448 (M+). Anal.
Calcd for C33H24N2. C, 88.39; H, 5.36; N, 6.25. Found: C, 88.22; H, 5.45; N, 6.08.
cis-2,4,5-Tris(β-naphthyl)imidazoline (2j):
1
This imidazoline was prepared in the general way and had mp 208-209°C (ethanol). H-NMR
(CD3SOCD3/TMS-500 MHz): 6.39 (2H, s), 6.92-7.03 (3H, m), 7.06-7.13 (2H, m), 7.14-7.23 (4H, m), 7.33
(2H, d, J=6.9 Hz), 7.46-7.51 (3H, m), 7.55-7.59 (2H, m), 7.76 (2H, d, J=8.5 Hz), 7.92-7.97 (3H, m), 8.82
(1H, m); 13C-NMR (CD3SOCD3/TMS-125.7 MHz): 65.16, 122.98, 124.31, 124.79, 124.86, 124.92, 125.19,
125.50, 126.40, 127.30, 127.36, 127.42, 128.09, 128.56, 130.57, 131.51, 132.85, 133.45, 165.73; IR (KBr):
3412 (-NH), 1620 (C=N) cm-1; MS m/z: 448 (M+). Anal. Calcd for C33H24N2. C, 88.39; H, 5.36; N, 6.25.
Found: C, 88.18; H, 5.48; N, 5.98.
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