Glycerol based ionic liquid with a boron core: A new highly efficient and reusable promoting medium for the synthesis of quinazolinones

Article abstract of DOI:10.1016/j.molliq.2013.01.013

A highly efficient and environmental benign procedure for the synthesis of 2,3-dihydroquinazolin-4(1H)-ones via the condensation of carbonyl compounds with 2-aminobenzamide using a glycerol based ionic liquid with a boron core as a new and reusable promoting medium is described. A broad range of substrates including aldehydes and ketone were condensed with 2-aminobenzamide. All reactions are completed in short times and the products are obtained in good to excellent yields. The reaction medium could be recycled and reused several times without any loss of efficiency. Moreover, presented procedure has been applied successfully for the synthesis of some novel bis(pyrazolinone) derivatives.

Full text of DOI:10.1016/j.molliq.2013.01.013

Journal of Molecular Liquids 180 (2013) 139–144
Contents lists available at SciVerse ScienceDirect
Journal of Molecular Liquids
journal homepage: www.elsevier.com/locate/molliq
Glycerol based ionic liquid with a boron core: A new highly efficient and reusable
promoting medium for the synthesis of quinazolinones
a
a
Hamid Reza Safaei a, , Mohsen Shekouhy
, Vahid Shafiee , Mansooreh Davoodi
⁎
a,b,⁎⁎
a
Department of Applied Chemistry, Faculty of Science, Shiraz Branch, Islamic Azad University, PO Box 71993-5, Shiraz, Iran
Young Researchers Club, Shiraz Branch, Islamic Azad University, Shiraz, Iran
b
a r t i c l e i n f o
a b s t r a c t
Article history:
A highly efficient and environmental benign procedure for the synthesis of 2,3-dihydroquinazolin-4(1H)-ones
via the condensation of carbonyl compounds with 2-aminobenzamide using a glycerol based ionic liquid with
a boron core as a new and reusable promoting medium is described. A broad range of substrates including alde-
hydes and ketone were condensed with 2-aminobenzamide. All reactions are completed in short times and the
products are obtained in good to excellent yields. The reaction medium could be recycled and reused several
times without any loss of efficiency. Moreover, presented procedure has been applied successfully for the synthe-
sis of some novel bis(pyrazolinone) derivatives.
Received 31 December 2012
Received in revised form 16 January 2013
Accepted 18 January 2013
Available online 8 February 2013
Keywords:
Glycerol
Ionic liquid
© 2013 Elsevier B.V. All rights reserved.
Quinazolinone
2-aminobenzamide
H[Gly2B]
Bis(pyrazolinone)
1. Introduction
Moreover, reductive condensation of 2-nitrobenzamide and alde-
hydes or ketones was also reported in the presence of low valence ti-
One of the most important classes of nitrogen heterocycles is
quinazoline and its derivatives that have recently been evaluated as
antagonists of various biological receptors, such as 5-HT5A related
diseases [1], calcitonin generelated peptide [2], and vasopressin V3
receptors [3]. Between various kinds of quinazoline derivatives,
2-substituted quinazolines show important biological activities such
as anti-inflammatory [4], antihypertensive [5], anticancer [6], antitumor
[7], and antibacterial [8]. Methaqualone (Fig. 1) is an anti-malarial drug
[9a] and currently being used for the assessment of the abuse liability of
sedative hypnotic drugs [9b]. Tiodazosin (Fig. 1), a hybrid of quinazoline
and [1,3,4]-oxadiazole heterocycles has been marketed as antihyper-
tensive agent [9c,d].
Based on the above facts, the synthesis of quinazoline derivatives
is currently of great interest in organic synthesis. The most popular
method for the synthesis of 2-sustituted quinazolines is based on
the condensation of 2-aminobenzamide with aromatic aldehydes cat-
alyzed by NH4Cl, AlCl3/ZnCl2, p-TSA, other Lewis acids, and asymmet-
ric Brönsted acids [10] or one-pot condensation of isatoic anhydride
and amines with aldehydes in organic solvents [11].
tanium [12].
Most of these methods have certain limitations such as tedious
processes, long reaction times, harsh reaction conditions, application
of volatile organic solvents, toxic reagents, non-reusability of the cat-
alyst and low yields of products.
Nowadays, more severe legislation and restrictions are ordained in
order to reduce of the environmental impact of man-made chemicals.
In this context, the ability of ionic liquids (ILs) as new reaction media,
to provide the requirements of environmental sustainability is re-
markable. The most important advantage of ILs is their lack of vapor
pressure relative to the traditional volatile molecular solvents, that
corroborate their efficiency about the incorporation in a sustainable
synthesis [17] (Green Chemistry principle 2) [13]. Moreover, their
low toxicity and limited environmental persistence (Green Chemistry
principles 3 and 10) [13] make them competent solvents for sustain-
able chemical processes. Another feature of ionic liquids is their abil-
ity to be reused many times. Over the last few years, there have been
several reviews published in which ionic liquids occupied a central
theme [14].
Glycerol, an organic liquid molecule that forms from the alkaline
hydrolysis of fats has gained special attention because of its unique
chemical and physical properties. Nowadays, this material is obtained
as a by-product of biodiesel synthesis via the transesterification of
seed oils with methanol. Glycerol is a green and biodegradable com-
pound. Moreover, this material is non-volatile under normal atmo-
spheric pressure and has a high boiling point. Besides, it is a nontoxic
⁎
Corresponding author. Tel.: +98 711 6402715; fax: +98 711 6412488.
⁎⁎ Correspondence to: M. Shekouhy, Department of Applied Chemistry, Faculty of Science,
Shiraz Branch, Islamic Azad University, PO Box 71993-5, Shiraz, Iran. Tel.: +98 711
6402715; fax: +98 711 6412488.
E-mail addresses: hrs@iaushiraz.net (H.R. Safaei), m.shekouhy@gmail.com
(M. Shekouhy).
0167-7322/$ – see front matter © 2013 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.molliq.2013.01.013

140
H.R. Safaei et al. / Journal of Molecular Liquids 180 (2013) 139–144
at 110 °C for 4 h. During this time, the byproduct water was removed
(a)
(b)
by azeotropic distillation. After this time, toluene was evaporated
under reduced pressure and glyceroboric acid was obtained as a color-
less viscous liquid [16].
O
NH2
O
O
N
N
N
N
N
N
N
3.2. General procedure for the synthesis of quinazolinones
S
N
O
2-Aminobenzamide (1 mmol) were added to the mixture of carbonyl
compound (1 mmol) in H[Gly2B] (0.5 g) in a 25 mL pyrex flask
connected to a condenser and the resulted mixture was stirred mag-
netically for the appropriate time (Table 1) at 60 °C. The reactions
were followed by thin layer chromatography (TLC) using hexane/
ethyl acetate (3:1) as a mobile phase. After completion of the reac-
tion, water (20 mL) was added and stirred magnetically for 5 min.
Insoluble crude products were filtered and recrystallized from EtOH.
To recover the H[Gly2B], after the isolation of insoluble products,
water was evaporated, and the remaining viscous liquid was washed
with methyl tert-butyl ether (5 mL) and dried under reduced pressure.
As H[Gly2B] is too hydrophilic, in order for the complete removal of
water, an additional lyophilization step was run. For this, recovered H
[Gly2B] was frozen in liquid nitrogen and lyophilized to near-dryness
over 2 days [20]. (H[Gly2B] was recovered in 98% yield).
O
Fig. 1. Chemical structures of (a) Methaqualone and (b) Tiadazosin.
(LD50 (oral rat)=12,600 mg kg−1) material that is used widely in cos-
metics such as face masks, skin creams, tooth paste etc.
In addition, boron is present in many foods and drinking water sup-
plies. Estimated human consumption of boron in the U.S. diet ranges
from 0.02 mg boron/day to more than 9 mg boron/day with an estimat-
ed average intake of 1.17 mg boron/day for men and 0.96 mg boron/day
for women. Recent evidence has suggested that boron may be an essen-
tial micronutrient. The US EPA considers boric acid to be low in acute tox-
icity based on studies in rats with an oral LD50 of 3450 mg kg−1 for male
rats and 4080 mg kg−1 for female rats.
Considering the biological importance and pharmaceutical appli-
cations of quinazolines and green behaviors of glycerol and impor-
tance of its derivatives in the development of more environmental
benign organic procedures, and along with our previous studies on
the application of glycerol and its derivatives in organic synthesis
[15], herein we report the application of a glycerol based ionic liquid
with a boron core as a highly efficient biodegradable and reusable
promoting medium for the synthesis of quinazolinone derivatives
(Scheme 1).
3.3. Selected spectral data
3.3.1. 1′H,2H-spiro[acenaphthylene-1,2′-quinazoline]-2,4′(3′H)-dione
(compound 3x)
White powder (m.p.=295–297 °C), υmax (KBr):,3470, 3340, 3025,
2960, 1710 cm−1 1H NMR (500 MHz, DMSO-d6): δ (ppm) 6.95–7.03
.
(m, 2H), 7.13 (d, J=7.5 Hz, 1H), 7.47–7.51 (m, 3H), 7.71 (d, J=7.3 Hz,
1H), 7.93 (d, J=8.0 Hz, 2H), 8.09–8.18 (m, 2H), 9.5 (s, 1H), 10.8 (s, 1H).
13C NMR (125 MHz, DMSO-d6): δ (ppm) 104.0, 113.5, 115.8, 116.5,
120.9, 124.8, 125.9, 127.3, 128.8, 128.9, 129.3, 129.9, 131.8, 132.5,
133.1, 143.1, 147.5, 165.9, 198.8. Anal. Calcd for C19H12N2O2: C, 75.99;
H, 4.03; N, 9.33%; found: C, 75.91; H, 4.09; N9.41%.
2. Method and material
Reagents and solvents were purchased from Merck, Fluka or Aldrich.
The IL was prepared according to the reported method [16]. Melting
points were determined in capillary tubes in an electro-thermal C14500
apparatus. The progress of the reaction and the purity of compounds
were monitored by TLC analytical silica gel plates (Merck 60 F250). All
known compounds were identified by comparison of their melting points
and 1H NMR data with those in the authentic samples. The 1H NMR
(500 MHz) and 13C NMR (125 MHz) were run on a Bruker Avance
DPX-250, FT-NMR spectrometer. Chemical shifts are given as a δ value
against tetramethylsylane as the internal standard and J values are
given in Hz. Microanalysis was performed on a Perkin-Elmer 240-B
microanalyzer. All experiments performed in this work were repeated
three times. The yield reported represents the average of the values
obtained for each reaction.
3.3.2. Bis(spiro-quinazoline) (compound 3y)
White powder, mp: >300 °C, υmax (KBr): 3450, 3390, 3020, 2975,
1700, 1650 cm−1. 1H NMR (500 MHz, DMSO-d6): δ (ppm) 1.09 (m, 4H),
1.47 (m, 4H), 6.8 (t, J=7.5 Hz, 2H), 7.08 (d, J=7.5 Hz, 2H), 7.51 (t, J=
7.5 Hz, 2H), 7.76 (d, J=7.5 Hz, 2H), 9.8 (s, 2H), 10.7 (s, 2H). 13C NMR
(125 MHz, DMSO-d6): δ (ppm) 21.8, 81.7, 112.5, 115.7, 116.8, 127.5,
132.9, 147.1, 166.6. Anal. Calcd for C20H20N4O2: C, 68.95; H, 5.79; N,
16.08%; found: C, 69.01; H, 5.83; N, 16.01%.
3.3.3. Ethyl 2-(2-methyl-4-oxo-1,2,3,4-tetrahydroquinazolin-2-yl)acetate
(compound 11a)
White powder, m.p.=227–229 °C, υmax (KBr): 3420, 3395, 3017,
3. Experimental
2950, 1705, 1675 cm−1 1H NMR (500 MHz, DMSO-d6): δ (ppm) 0.97
.
(t, J=7.8 Hz, 3H), 1.12 (s, 3H), 2.56 (d, J=15.5 Hz, 1H), 2.68 (d, J=
15.5 Hz, 1H), 3.71 (m, 2H), 6.83 (t, J=7.3 Hz, 1H), 7.03 (d, J=7.3 Hz,
1H), 7.53 (t, J=7.3 Hz, 1H), 7.76 (d, J=7.3 Hz, 1H), 9.15 (s, 1H),
10.31 (s, 1H). 13C NMR (125 MHz, DMSO-d6): δ (ppm) 14.6, 24.7,
45.5, 62.7, 73.4, 112.1, 116.3, 117.2, 128.5, 132.3, 147.3, 164.3, 171.9.
3.1. General procedure for the synthesis of H[Gly2B]
Boric acid (61.83 g, 1 mol) and glycerol (190 g, 2 mol) were added
to a 1 L flask containing toluene (500 mL) and the mixture was stirred
O
O
O
R1
R2
NH
R1
R2
bis(glycerol)boric acid (H[Gly2B])
60 oC
NH2
+
N
H
NH2
(1)
(2)
(3a-x)
Scheme 1. Synthesis of quinazolinone derivatives using H[Gly2B] as a highly efficient and reusable promoting medium.

H.R. Safaei et al. / Journal of Molecular Liquids 180 (2013) 139–144
141
Table 1
Synthesis of quinazolinone derivatives using H[Gly2B] as a highly efficient, reusable glycerol based promoting medium.
Entry
R1
R2
Time (min)
Yield (%)a
M.P (°C)
Found
Reported
3a
3b
3c
3d
3e
3f
3 g
3 h
3i
C6H5
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
10
10
10
15
10
15
25
25
15
5
90
91
91
90
90
90
89
90
91
92
91
91
90
89
87
90
90
90
91
83
89
90
90
226–228
205–207
198–199
227–228
277–278
228–229
181–182
170–171
207–209
>300
(225–226) [18]
(207–208) [18]
(197–198) [18]
(229–230) [18]
(279–280) [18]
(229–231) [18]
(183–184) [18]
(173–174) [18]
(205–206) [19]
(310–313) [18]
(180–182) [18]
(350–351) [18]
(194–196) [19]
(166–167) [11a]
(187–188) [11e]
(143–144) [19]
(183–184) [19]
(222–224) [19]
(192–195) [19]
(203–205) [19]
258–259 [19]
4-Cl-C6H4
4-Br-C6H4
3-Br-C6H4
4-F-C6H4
4-CH3-C6H4
4-OCH3-C6H4
2-OCH3-C6H4
2-Cl-C6H4
4-NO2-C6H4
3-NO2- C6H4
4-CN-C6H4
4-CF3-C6H4
2-Furyl
2-pyridyl
CH3(CH2)3
CH3
C6H5
CH3(CH2)2
C6H5
3j
3 k
3 l
3 m
3n
3o
3p
3q
3r
3 s
3 t
3u
3v
3w
5
10
5
182–184
>300
193–195
165–166
185–186
145–146
181–182
219–221
191–193
200–203
260–261
219–221
15
25
25
20
25
20
55
30
30
30
CH3
CH3
CH3
C6H5
-CH2CH2CH2CH2-
-CH2CH2CH2CH2CH2-
216–218 [19]
261–263 [21]
3x
30
50
91
87
295–297
–
–
3yb
>300
11a
180
85
227–229
–
11bc
11cb
180
360
71
78
220–221
–
–
>300
a
Isolated yields.
b
c
Reaction conditions: diketone (1 equivalent), 2-aminobenzamide (2 equivalents).
Reaction conditions: diketone (1 equivalent), 2-aminobenzamide (1 equivalents).
Anal. Calcd for C13H16N2O3: C, 62.89; H, 6.50; N, 11.28%; Found: C,
63.95; H, 6.55; N, 11.38%.
4. Results and discussion
In the first step, bis(glycerol)boric acid, H[Gly2B], was synthesized
using the synthetic route described in a recent patent [16]. For this pur-
pose, glycerol was added to the appropriate quantity of boric acid in tol-
uene, and the reaction was allowed to proceed at reflux temperature.
The byproduct water was continuously removed from the reaction by
azeotropic distillation, obtaining a highly viscous uncolored liquid. The
structure of the resulted ionic liquid has been demonstrated with mi-
croanalysis, electrospray ionization mass spectroscopy (ESI-MS) and
IR and its thermal stability is investigated by TG analysis. The mass spec-
trum of H[Gly2B] dissolved in acetonitrile contains a strong peak at m/e
191 attributable to a bis(glycerol)borate, which is shown to be in good
agreement with the results obtained from TG analysis and conventional
elemental analysis. Carbon content of the H[Gly2B] was 29.41% by con-
ventional elemental analysis that is in appropriate agreement with a 1:2
adduct of glycerol and boric acid. The thermal stability of H[Gly2B] was
also investigated using a self-made TG analysis instrument, and the
results are shown in Fig. 2. Fig. 2 shows the thermogram of the sample
at an air flow of 3 mL min−1 and temperature ramp of 2 °C min−1. Fol-
lowing the thermogram, the decrease observed in the slope of the dia-
gram, starting at around 260 °C can be related to the loss of the
covalently bound organic groups.
3.3.4. 2-Methyl-2-(2-oxopropyl)-2,3-dihydroquinazolin-4(1H)-one
(compound 11b)
White powder, m.p.=220–221 °C, υmax (KBr): 3425, 3395, 3020,
2980, 1710, 1685 cm−1 1H NMR (500 MHz, DMSO-d6): δ (ppm) 1.25
.
(s, 3H), 2.46 (s, 3H), 2.76 (d, J=16.0 Hz, 1H), 2.99 (d, J=16.0 Hz,
1H), 6.87 (t, J=7.5 Hz, 1H), 7.03 (d, J=7.5 Hz, 1H), 7.56 (t, J=7.5 Hz,
1H), 7.81 (d, J=7.5 Hz, 1H), 9.31 (s, 1H), 10.04 (s, 1H). 13C NMR
(125 MHz, DMSO-d6): δ (ppm) 23.5, 27.8, 57.9, 68.3, 112.8, 116.6,
117.9, 127.5, 133.1, 146.4, 196.02. Anal. Calcd for C12H14N2O2: C,
66.04; H, 6.47; N, 12.84%; Found: C, 66.11; H, 6.58; N, 12.75%.
3.3.5. 2,2′-Methylenebis(2-methyl-2,3-dihydroquinazolin-4(1H)-one)
(compound 11c)
White powder, m.p.=>300 °C, υmax (KBr): 3440, 3410, 3010,
2950, 1710, 1670 cm−1 1H NMR (500 MHz, DMSO-d6): δ (ppm) 1.89
.
(s, 6H), 2.08 (s, 2H), 6.87 (t, J=7.6 Hz, 2H), 7.08 (d, J=7.5 Hz, 2H),
7.55 (t, J=7.7 Hz, 2H), 7.89 (d, J=7.6 Hz, 2H), 9.16 (s, 2H), 10.23
(s, 2H). 13C NMR (125 MHz, DMSO-d6): δ (ppm) 24.8, 61.3, 67.8, 112.6,
116.5, 117.7, 128.3, 132.9, 146.1, 165.9. Anal. Calcd for C19H20N4O2:
C, 67.84; H, 5.99; N, 16.66%; Found: C, 67.95; H, 6.07; N, 16.72%.

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H.R. Safaei et al. / Journal of Molecular Liquids 180 (2013) 139–144
Fig. 2. TG analysis of H[Gly2B].
HO
tains two peaks in ca. 1:4 ratio at 28.05 and 23.8 ppm respectively.
Based on their illustrations, we suggest that H[Gly2B] is presented in
two forms that are in equilibrium (Scheme 2).
OH
OH
OH
OH
O
O
O
In the next step, to evaluate the efficiency of H[Gly2B] for the synthesis
of quinazolinone derivatives, various kinds of carbonyl compounds were
condensed with 2-aminobenzamide in the presence of H[Gly2B] as a
promoting medium (Scheme 1). For this purpose, 2-aminobenzamide
(1 mmol) were added to the mixture of carbonyl compound (1 mmol)
and H[Gly2B] (0.5 g) and the resulting mixture was stirred at 60 °C. The
obtained results are summarized in Table 1.
O
O
O
HO
OH
H
H
B
B
B
+
O
O
OH
OH
HO
Scheme 2. Two possible structures of H[Gly2B] (for more information see Ref. [17]).
As it can be seen from Table 1, all reactions proceeded efficiently
and the desired products were produced in good to excellent yields in
relatively short reaction times without formation of any side products.
Aromatic aldehydes having electron withdrawing groups (Table 1, en-
tries 3j, 3k, 3l and 3m) reacted at faster rate compared with those that
were substituted with electron releasing groups (Table 1, entries 3f,
As it is shown in Scheme 2 there are two possible coordination
forms between the glycerol and boric acid. Recently Chiappe et al. in-
vestigated the structure of H[Gly2B] based on its 11B and 13C NMR
spectra [17]. The 11B NMR spectrum of H[Gly2B] in dried CD3CN con-
O
O
O
O
O
NH
O
NH
N
(6)
NH
(4)
N
H
H
N
30 min
H
30 min
90%
(3w)
(3u)
89%
O
NH2
NH2
O
O
O
H[Gly2B]
60 o
O
O
C
NH
NH
(7)
(5)
N
H
N
H
30 min
91%
30 min
90%
(3x)
(3v)
O
Scheme 3. The synthesis of spiro-quinazolinones using H[Gly2B] as a highly efficient promoting medium.

H.R. Safaei et al. / Journal of Molecular Liquids 180 (2013) 139–144
143
O
O
O
O
NH
HN
H[Gly2B]
60 oC
NH2
+
50 min
87%
NH2
NH
HN
O
(1)
(8)
(3y)
Scheme 4. The condensation of 2-aminobenzamide (1) and cyclohexane-1,4-dione (8) in
the presence of H[Gly2B] as a highly efficient glycerol based promoting medium.
3g and 3h). Besides, our methodology has been used successfully for
heteroaromatic aldehydes, and corresponding product was obtained
in excellent yields and without any byproduct (Table 1, entries 3n and
3o). As it is clear from the obtained results, presented methodology
can be use in order of aliphatic and aromatic aldehydes as well as
ketones.
We also applied our method for the synthesis of some
spiro-quinozalinones via the condensation of cyclic ketones such as
cyclopentanone (4), cyclohexanone (5), isatin (6) and acenaphthene-
quinone (7) with 2-aminobenzamide (1) in the presence of H[Gly2B]
at 60 °C (Scheme 3).
Graph 1. Reusability of H[Gly2B] in the synthesis of compound (3a).
was added and stirred magnetically for 5 min. Insoluble crude products
were filtered and recrystallized from EtOH. To recover the H[Gly2B],
after the isolation of insoluble products, water was evaporated, and
the remaining viscous liquid was washed with methyl tert-butyl ether
(5 mL) and dried under reduced pressure. As H[Gly2B] is too hydrophil-
ic, in order for the complete removal of water, an additional lyophiliza-
tion step was run. For this, recovered H[Gly2B] was frozen in liquid
nitrogen and lyophilized to near-dryness over 2 days.20 The recovered
H[Gly2B] was reused twelve times for the synthesis of compound (3a)
and no loss of efficiency was observed (Graph 1).
Moreover bis(spiro-quinazolinone) (3y) were synthesized via
the condensation reaction of cyclohexane-1,4-dione (8) and 2-
aminobenzamide (1) in the presence of H[Gly2B] for the first time
(Scheme 4).
Besides, we examined our methodology for the condensation of
2-aminobenzamide with 1,3-dicarbonyl compounds such as ethyl-
acetoacetate (9) and acetylacetone (10) and the obtained results are
shown in Scheme 5.
5. Conclusion
In summary, we have reported a highly efficient and green method
for the synthesis of quinazolinone derivatives using H[Gly2B] as a highly
efficient and reusable glycerol based reaction medium. The method
presented, avoids the use of hazardous catalysts or solvents. The prom-
ising points for the presented methodology are efficiency, generality,
high yield, short reaction time, cleaner reaction profile, ease of product
isolation, simplicity, potential for recycling of the reaction medium, and
finally agreement with the green chemistry protocols, which all make it
a useful and attractive process for the synthesis of quinazolinone de-
rivatives. Moreover, the presented method is applicable for the syn-
thesis of more complex structures such as spiro-quinazolinones and
bis(spiro-quinazolinone)s.
As it is shown in Scheme 5, the condensation reaction between
2-aminobenzamide and enolizable 1,3-dicarbonyl compounds is more
difficult and relatively lower yields were obtained in these cases. Only
product (11b) and trace amounts of (11c) were obtained when
acetylacetone (10) was treated with 1 equivalent of 2-aminobenzamide,
whereas product 11c was the major product when 2 equivalents of
2-aminobenzamide were treated with acetylacetone (10) in the presence
of H[Gly2B] at 60 °C.
The possibility of recycling the reaction medium was examined for
the synthesis of compound (3a) using the reaction between benzal-
dehyde (1 mmol) and 2-aminobenzamide (1) (1 mmol) in H[Gly2B]
(0.5 g) at 60 °C. After completion of the reaction, water (20 mL)
O
O
O
O
O
O
O
OEt
NH
NH
OEt
NH2
(10)
(9)
O
NH
O
NH
NH2
180 min
85%
180 min
71%
(11a)
(11b)
H[Gly2B]
60 oC
O
O
360 min
78%
(10)
H
N
H
N
O
NH
HN
(11c)
O
Scheme 5. The condensation of 2-aminobenzamide with 1,3-dicarbonyl compounds in the presence of H[Gly2B] as a highly efficient promoting medium.

144
H.R. Safaei et al. / Journal of Molecular Liquids 180 (2013) 139–144
(c) P. Salehi, M. Dabiri, M. Baghbanzadeh, M. Bahramnejad, Synthetic Communi-
Acknowledgment
cations 36 (2006) 2287–2292;
(d) J.X. Chen, W.K. Su, H.Y. Wu, M.C. Liu, C. Jin, Green Chemistry 9 (2007)
972–975;
(e) J. Chen, D. Wu, F. He, M. Liu, H. Wu, J. Ding, W. Su, Tetrahedron Letters 49
(2008) 3814–3818;
We appreciate the Islamic Azad University (Shiraz branch) Re-
search Councils for the financial support of this work.
(f) P. Salehi, M. Dabiri, M.A. Zolfigol, M. Baghbanzadeh, Synlett (2005) 1155–1157;
(g) H.L. Yale, Journal of Heterocyclic Chemistry 14 (1977) 1357–1359.
[12] (a) D.Q. Shi, L.C. Rong, J.X. Wang, X.S. Wang, S.J. Tu, H.W. Hu, Chemical Journal of
Chinese Universities 25 (2004) 2051–2054;
References
[1] A. Alanine, L.C. Gobbi, S. Kolczewski, T. Luebbers, J.-U. Peters, L. Steward, U.S. Patent
US 2006293350 A1, 2006; Chem. Abstr. 146 (2006) 100721.
[2] P.V. Chaturvedula, L. Chen, R. Civiello, A.P. Degnan, G.M. Dubowchik, X. Han, X.J.
Jiang, J.E. Macor, G.S. Poindexter, G.O. Tora, G. Luo, U.S. Patent US 2007149503
A1 2007; Chem. Abstr. 147 (2007) 118256.
(b) D.Q. Shi, L.C. Rong, J.X. Wang, Q.Y. Zhuang, X.S. Wang, H.W. Hu, Tetrahedron
Letters 44 (2003) 3199–3201;
(c) D.Q. Shi, C.L. Shi, J.X. Wang, L.C. Rong, Q.Y. Zhuang, X.S. Wang, Journal of
Heterocyclic Chemistry 40 (2005) 173–183;
[3] J. Letourneau, C. Riviello, K.-K. Ho, J.-H. Chan, M. hlmeyer, P. Jokiel, I. Neagu, J.R.
Morphy, S.E. Napier, Chemical Abstracts 145 (2006) 315012, (PCT Int. Appl. WO
2006095014 A1 2006).
[4] V. Alagarsamy, S.V. Raja, K. Dhanabal, Bioorganic & Medicinal Chemistry 15
(2007) 235–241.
[5] V. Alagarsamy, U.S. Pathak, Bioorganic & Medicinal Chemistry 15 (2007) 3457–3462.
[6] V. Murugan, M. Kulkarni, R.M. Anand, E.P. Kumar, B. Suresh, V.M. Reddy, Asian
Journal of Chemistry 18 (2006) 900–906.
[7] A.A.A. Godfrey, Chemical Abstracts 142 (2005) 198095, (PCT Int. Appl. WO
2005012260 A2 2005).
(d) C.L. Yoo, J.C. Fettinger, M.J. Kurth, The Journal of Organic Chemistry 70 (2005)
6941–6943;
(e) D. Shi, J. Wang, L. Rong, Q. Zhuang, S. Tu, H. Hu, Journal of Chemical Research
(2003) 671–673;
(f) G. Bonola, P. Da Re, M.J. Magistretti, E. Massarani, I. Setnikar, Journal of Medicinal
Chemistry 11 (1968) 1136–1139;
(g) D. Shi, G. Dou, Y. Zhou, Synthesis (2008) 2000–2006.
[13] P.T. Anastas, M.M. Kirchhoff, Accounts of Chemical Research 35 (2002) 686–694.
[14] (a) P. Wasserscheid, W. Keim, Angewandte Chemie, International Edition 39
(2000) 3772–3789;
[8] P. Selvam, K. Girija, G. Nagarajan, E. De Clerco, Indian Journal of Pharmaceutical
Sciences 67 (2005) 484–487.
[9] (a) I.K. Kacker, S.H. Zaheer, Journal of the Indian Chemical Society 28 (1951) 344–349;
(b) A.H. Amin, D.R. Mehta, S.S. Samarth, Progress in Drug Research 14 (1970)
218–225;
(b) T. Welton, Chemical Reviews 99 (1999) 2071–2084;
(c) C. Chiappe, D. Pieraccini, Journal of Physical Organic Chemistry 18 (2005)
275–297;
(d) H. Olivier-Bourbigou, L. Magna, Journal of Molecular Catalysis A: Chemical
(2002) 182–183;
(c) R.A. Partyka, R.R. Crenshaw, U.S. Patent 4001238, 1977.
(d) S. Vardan, S. Mookherjee, R. Eich, Clinical Pharmacy and Therapeutics 34
(1983) 290–297.
(e) S.M.S. Chauhan, N. Jain, A. Kumar, S. Chauhan, Tetrahedron 61 (2005) 1015–1060;
(f) J.L. Scott, C. Shahana, R.S. Mohan, Tetrahedron 63 (2007) 2363–2389.
[15] H.R. Safaei, M. Shekouhy, S. Rahmanpoor, A. Shirinfeshan, Green Chemistry 14
(2012) 1696–1704.
[16] S.K. Ahuja, T.W. Smith, European Patent Application EP1310532A1, 2006; U.S.
Patent application US65858161, 2006.
[10] (a) A. Shaabani, A. Maleki, H. Mofakham, Synthetic Communications 38 (2008)
3751–3759;
(b) M. Dabiri, P. Salehi, A.A. Mohammadi, M. Baghbanzadeh, Synthetic Commu-
nications 35 (2005) 279–287;
(c) Y. Gao, U.S. Patent US 6274383 B1, 2001.
[17] C. Chieppe, F. Sgnori, G. Valentini, L. Marchetti, Ch.S. Pomelli, F. Bellina, Journal of
Physical Chemistry B 114 (2010) 5082–5088.
(d) M. Rueping, A.P. Antonchick, E. Sugiono, K. Grenader, Angewandte Chemie,
International Edition 48 (2009) 908–910;
[18] Sh. Rostamizadeh, A.M. Amini, R. Arya, Synthetic Communications 38 (2008)
3567–3576.
(e) H.L. Yale, M. Kalkstein, Journal of Medicinal Chemistry 10 (1967) 334–336.
[11] (a) M. Baghbanzadeh, P. Salehi, M. Dabiri, G. Kozehgarya, Synthesis (2006) 344–348;
(b) M. Dabiri, P. Salehi, S. Otokesh, M. Baghbanzadeh, G. Kozehgarya, A.A.
Mohammadi, Tetrahedron Letters 46 (2005) 6123–6126;
[19] R.A. Bunce, B. Nammalwar, Journal of Heterocyclic Chemistry 48 (2011) 991–997.
[20] P. Cintas, J.L. Luche, Green Chemistry 1 (1999) 115–125.
[21] M. Dabiri, A.A. Mohammadi, H. Qaraat, Monatshefte für Chemie 140 (2009)
401–404.