A practical and efficient synthesis of 2,5-disubstituted-3,5-dihydro- imidazol-4-ones from oxazolones

Article abstract of DOI:10.1080/00397911.2011.581406

An alternative procedure for the synthesis of 2,5-disubstituted-3,5- dihydro-imidazol-4-ones from substituted oxazolones was evaluated. The initial oxazolone ring-opening reaction was examined with a variety of ammonia source compounds followed by the sub

Full text of DOI:10.1080/00397911.2011.581406

This article was downloaded by: [Fondren Library, Rice University ]
On: 08 August 2012, At: 09:08
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered
office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Synthetic Communications: An
International Journal for Rapid
Communication of Synthetic Organic
Chemistry
Publication details, including instructions for authors and
subscription information:
http://www.tandfonline.com/loi/lsyc20
A Practical and Efficient Synthesis
of 2,5-Disubstituted-3,5-dihydro-
imidazol-4-ones from Oxazolones
Flavio Chavez a , Caslin Pavy a , Thomas Williamson a & Thomas
Cleary a
a Pharmaceutical Technical Development Actives (PTDA-FL), Roche
Carolina Inc., Florence, South Carolina, USA
Accepted author version posted online: 12 Jan 2012. Version of
record first published: 18 Jul 2012
To cite this article: Flavio Chavez, Caslin Pavy, Thomas Williamson & Thomas Cleary (2012): A
Practical and Efficient Synthesis of 2,5-Disubstituted-3,5-dihydro-imidazol-4-ones from Oxazolones,
Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic
Chemistry, 42:22, 3321-3327
To link to this article: http://dx.doi.org/10.1080/00397911.2011.581406
PLEASE SCROLL DOWN FOR ARTICLE
Full terms and conditions of use: http://www.tandfonline.com/page/terms-and-conditions
This article may be used for research, teaching, and private study purposes. Any
substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing,
systematic supply, or distribution in any form to anyone is expressly forbidden.
The publisher does not give any warranty express or implied or make any representation
that the contents will be complete or accurate or up to date. The accuracy of any
instructions, formulae, and drug doses should be independently verified with primary
sources. The publisher shall not be liable for any loss, actions, claims, proceedings,
demand, or costs or damages whatsoever or howsoever caused arising directly or
indirectly in connection with or arising out of the use of this material.

Synthetic Communications1, 42: 3321–3327, 2012
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2011.581406
A PRACTICAL AND EFFICIENT SYNTHESIS OF
2,5-DISUBSTITUTED-3,5-DIHYDRO-IMIDAZOL-4-ONES
FROM OXAZOLONES
Flavio Chavez, Caslin Pavy, Thomas Williamson, and
Thomas Cleary
Pharmaceutical Technical Development Actives (PTDA-FL), Roche
Carolina Inc., Florence, South Carolina, USA
GRAPHICAL ABSTRACT
Abstract An alternative procedure for the synthesis of 2,5-disubstituted-3,5-dihydro-
imidazol-4-ones from substituted oxazolones was evaluated. The initial oxazolone ring-
opening reaction was examined with a variety of ammonia source compounds followed by
the subsequent 3,5-dihydro-imidazol-4-one cyclization reaction, which was carried out with
either an organic or inorganic base in aprotic solvents. In this article, we report the results
of an efficient and straightforward procedure for the synthesis of 2,5-disubstituted-3,5-
dihydro-imidazol-4-ones that gives satisfactory yield and quality.
Keywords Azlactone; DBU; Erlenmeyer reaction; imidazolone; oxazolone; potassium
carbonate
INTRODUCTION
Unsaturated 2,5-disubstituted-3,5-dihydro-imidazol-4-ones are interesting
compounds that have shown potential biological applications.[1] Therefore, these het-
erocycles have been the focused target intermediates of several groups in the field of
combinatorial chemistry and drug discovery. The most common approaches to access
these compounds are from oxazolones, glycine ester–imidic acid esters, and other
condensation reactions.[2] As recently reported,[3] ammonium acetate was utilized
as the source of ammonia in the synthesis of 2,5-disubstituted-3,5-dihydro-imidazol-
4-ones using microwave techniques. The document states that the first stage of the
reaction involves the oxazolone 1 ring opening by ammonia to give the carbamoyl
Received April 8, 2011.
Address correspondence to Flavio Chavez, Pharmaceutical Technical Development Actives
(PTDA-FL), Roche Carolina Inc., 6173 East Old Marion Highway, Florence, SC 29506-9330, USA.
E-mail: flavio.chavez_lopez@roche.com
3321

3322
F. CHAVEZ ET AL.
Scheme 1. Synthesis of 2,5-disubstituted-3,5-dihydro-imidazol-4-ones: (a) NH4OAc, graphite, MW 600W.
arylvinyl benzamide intermediate 2, followed by an intramolecular condensation
dehydration reaction to obtain the respective imidazolone 3 (Scheme 1). With this
methodology as background, we attempted to develop an alternative procedure for
the synthesis of these compounds using oxazolones as the starting material, which
are readily available from the improved Erlenmeyer reaction in 2-methyl tetrahydro-
furan (Me–THF).[4] At the same time, we hoped to demonstrate that this procedure
could be suitable for scaling up to supply gram quantities of 3.
RESULTS AND DISCUSSION
To find the best reaction conditions for the oxazolone ring-opening reaction,
several ammonia candidates were tested, including ammonium acetate, formate, sul-
famate, and carbamate (Scheme 2). It was found that the aminolysis reaction pro-
ceeded quickly to completion with ammonium acetate and ammonium carbamate.
However, ammonium formate reacted very slowly, and ammonium sulfamate did
not react at all (Table 1, entries 1–4). Therefore, ammonium acetate and carbamate
were selected to proceed with the next step.
The intramolecular cyclization reaction has been previously reported in reflux-
ing pyridine.[5] We found that running the reaction in Me-THF while using a stronger
organic base, such as diisopropylethylamine (Hunig’s base) or 1,8-diazabicyclo[5.4.0]
undec-7-ene (DBU), was also viable. However, DBU provided better conversion than
Hunig’s base (Table 2, entries 1 and 2).
The cyclization reaction with DBU proceeded faster when using intermediate 2a
from the ring-opening reaction with ammonium carbamate than 2a from ammonium
acetate (Table 2, entries 2 and 3). When the solvent was changed to dimethyiforma-
mide (DMF), the rate of conversion to 3a was greatly increased (1 h vs. 4 h) with the
use of ammonium carbamate (Table 2, entries 4 and 5). In addition, when the cycliza-
tion reaction was examined with potassium carbonate (K2CO3) in dimethylsubfoxide
(DMSO), similar results were obtained.
Scheme 2. Evaluation of reaction conditions for aminolysis and cyclization stages.

2,5-DISUBSTITUTED-3,5-DIHYDRO-IMIDAZOL-4-ONES
3323
Table 1. Evaluation of ammonia source for oxazolone 1a ring opening
Aminolysis reaction
Entry
Ammoniuma
Solvent
Time (h)
Area (%)b
1
2
3
4
Acetate
Me-THF
Me-THF
Me-THF
Me-THF
1
1.5
8
97.3
94.2
90.3
0
Carbamate
Formate
Sulfamate
8
aAmmonia source ¼ 2 equiv.
bConversion by HPLC.
Based on these results, the ammonium carbamate–DBU–DMF procedure was
tested with a variety of substituted oxazolones[4] (Scheme 3). The oxazolone (1a–k),
ammonium carbamate, triethylamine (TEA), and DMF were combined at 55–60 ꢀC,
and after complete aminolysis, the carbamoyl intermediate (2a–k) was treated with
DBU at 90 ꢀC. Upon reaction completion, the mixture was diluted with water to
allow the product to crystallize (Table 3, entries 1–11). The observed aminolysis reac-
tion took 30 min; meanwhile, the imidazolone cyclization reaction took anywhere
from 1 to 3 h. The overall yield ranged from 88 to 97%, with product quality >98
area% [high-performance liquid chromatography (HPLC)]. In a similar way, the
ammonium carbamate–K2CO3–DMSO procedure was carried out with selected oxa-
zolones including a gram-scale run (Table 3, entries 12–17).
Table 2. Organic base and solvent evaluation of imidazolone cyclization reaction
Cyclization reaction
Entry
Ammoniuma
Solvent
Base
Time (h)
Area (%)b
1
2
3
4
5
Acetate
Acetate
Me-THF
Me-THF
Me-THF
DMF
Hunig
DBU
DBU
DBU
DBU
12
12
4
49.6
84.9
92.7
70.6
96.7
Carbamate
Acetate
Carbamate
10
1
DMF
aAmmonium source used for carbamoyl intermediate 2a.
bConversion by HPLC.
Scheme 3. General reaction conditions. Reagents: (a) NH2CO2NH4 in DMF or DMSO; (b) DBU or
K2CO3.

3324
F. CHAVEZ ET AL.
Table 3. General reaction conditions and results of the synthesis of 2,5-
disubstituted-3,5-dihydro-imidazol-4-ones
Reaction time (h)
Isolated
Aminolysisa Cyclizationb yield (%) Imidazolone
Oxazolone
1, Ar¼
Entry
1
2
Ph-
2-Cl-Ph-
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
1.0
0.5
0.5
1
1.5
2
92
90
87
91
94
92
93
88
93
89
93
92
94
93
95
95
94
3a
3b
3c
3d
3e
3f
3
3-NO2-Ph-
4-F-Ph-
4-Br-Ph-
4
1.5
1
5
6
4-MeO-Ph-
4-Me-Ph-
4-NO2-Ph-
2-Thiophenyl-
2-Furanyl-
4-Diphenyl-
Ph-
1.5
1
7
3g
3h
3i
8
1
9
2
10
11
12
13
14
15
16
17
1
3j
1
3k
3a
3b
3c
3e
3i
2c
1c
1c
1c
3c
2c
2-Cl-Ph-
3-NO2-Ph-
4-Br-Ph-
2-Thiophenyl-
2-Furanyl-d
3j
a0.8 mol% of ammonium carbamate.
bDBU as base (0.35 equiv except when noted).
cK2CO3 as base (0.5 equiv).
dScale up run (20 g).
CONCLUSION
We have developed a practical and efficient method for the synthesis of 2,5-
disubstituted-3,5-dihydro-imidazol-4-ones. Ammonium carbamate was an excellent
source of ammonia at the oxazolone ring-opening stage, while the imidazolone cycli-
zation stage was successfully executed using either DBU or potassium carbonate in
an aprotic solvent. Both methods gave satisfactory product yield and quality.
EXPERIMENTAL
All chemicals were purchased from Alfa Aesar, Acros, and=or Aldrich. Melting
points were determined in a Melt-Temp 3.0 Thermo Scientific apparatus at 5 ꢀC=min.
1H NMR and 13C NMR were recorded on a 400-MHz Varian NMR. Reaction
monitoring and product assay were performed on an Agilent Technologies 1200
HPLC instrument.
General DBU Procedure: 2-Phenyl-5-[1-phenylmethylidene]-3,5-
dihydro-imidazol-4-one (3a)
A mixture of oxazolone 1a (3.0 g, 12 mmol), DMF (9 mL), triethylamine (1 g,
10 mmol), and ammonium carbamate (0.75 g, 10 mmol) was heated to 55 ꢀC and held
for 30 min. The reaction was monitored for completion by HPLC. DBU (0.65 g,
4.2 mmol) was added to the solution via syringe, and the temperature was increased

2,5-DISUBSTITUTED-3,5-DIHYDRO-IMIDAZOL-4-ONES
3325
to 90 ꢀC and held for 1 h. Upon reaction completion, which was confirmed by HPLC,
the mixture was cooled to 60–70 ꢀC and water was added dropwise (35 mL) while
keeping the temperature >60 ꢀC. The orange slurry was slowly cooled to 20 ꢀC and
held for 2 h. 2-Phenyl-5-[1-phenylmethylidene]-3,5-dihydro-imidazol-4-one (3a) if
was collected by vacuum filtration and washed with 1:5 methanol=water (5 ꢀC)
followed by water. The product was dried at 55 ꢀC under vacuum for >12 h to give
2.74 g of a yellow solid (91%).
General Potassium Carbonate Procedure: 2-Pheny-5-[1-furan-2-yl-
methylidene]-3,5-dihydro-imidazol-4-one (3j)
A mixture of 4-[1-Furan-2-yl-meth-(Z)-ylidene]2-phenyl-4H-oxazol-5one (1j)
(20 g, 83.6 mmol), ammonium carbamate (5.22 g, 66.9 mmol), and DMSO (84 mL)
was stirred at room temperature. Triethylamine (6.77 g, 66.9 mmol) was added,
and the mixture was slowly heated to 55 ꢀC for a 30 min hold before taking a sample
for HPLC. Potassium carbonate (5.36 g, 41.8 mmol) was added to the dark solution,
and the temperature was increased to 90–93 ꢀC and held for 2 h. Upon reaction com-
pletion, confirmed by HPLC, the mixture was cooled to 60–65 ꢀC, and water was
added dropwise (165 mL) while keeping the temperature >60 ꢀC. The brown slurry
was held at 65 ꢀC for 30 min and then slowly cooled to 20 ꢀC. 2-Phenyl-5-[1-furan-2-
yl-meth-(Z)-ylidene]-3,5-dihydro-imidazol-4-one (3j) if was collected by vacuum fil-
tration and washed with 1:1 ethanol=water (ꢁ10 ꢀC) followed by water. The product
was dried at 65ꢀC under vacuum for >12 h to give 18.8 g of a yellow solid (94%).
Data
2-Phenyl-5-[1-phenyl-meth-(Z)-ylidene]-3,5-dihydro-imidazol-4-one (3a).
1
Mp: found 277–278 ꢀC; lit. 272–273 ꢀC[3]; H NMR (500 MHz, DMSO) d 12.12 (s,
1H), 8.33 (d, J ¼ 7.4, 2H), 8.19 (d, J ¼ 7.1, 2H), 7.66 (t, J ¼ 7.2, 1H), 7.61 (t,
J ¼ 7.3, 2H), 7.50 (t, J ¼ 7.4, 2H), 7.44 (t, J ¼ 7.3, 1H), 7.05 (s, 1H); 13C NMR
(126 MHz, DMSO) d 172.50, 161.36, 140.92, 134.83, 133.02, 132.53, 130.46,
129.49, 129.21, 128.42, 127.87, 125.52.
2-Phenyl-5-[1-(2-chlorophenyl)-meth-(Z)-ylidene]-3,5-dihydro-imidazol-
4-one (3b). Mp: found 262–263 ꢀC; lit. (268–269 ꢀC)[6]; 1H NMR (500 MHz,
DMSO) d 12.27 (s, 1H), 9.05 (d, J ¼ 7.9, 1H), 8.20 (d, J ¼ 7.3, 2H), 7.68 (t, J ¼ 7.3,
1H), 7.64–7.57 (m, 3H), 7.52 (t, J ¼ 7.5, 1H), 7.45 (t, J ¼ 6.9, 1H), 7.30 (s, 1H); 13C
NMR (126 MHz, DMSO) d 172.42, 162.98, 142.27, 135.28, 133.51, 133.41, 132.13,
131.74, 130.23, 129.53, 128.15, 128.10, 128.06, 118.82.
2-Phenyl-5-[1-(3-nitrophenyl)-meth-(Z)-ylidene]-3,5-dihydro-imidazol-4-
1
one (3c). Mp: found 249–250 ꢀC; lit. (261–262 ꢀC)[7]; H NMR (500 MHz, DMSO)
d 12.25 (s, 1H), 9.32 (s, 1H), 8.63 (d, J ¼ 7.8, 1H), 8.23 (d, J ¼ 8.2, 1H), 8.20 (d,
J ¼ 7.1, 2H), 7.76 (t, J ¼ 8.0, 1H), 7.69 (t, J ¼ 7.3, 1H), 7.63 (t, J ¼ 7.3, 2H), 7.16
(s, 1H); 13C NMR (126 MHz, DMSO) d 172.25, 162.94, 148.56, 142.63, 138.30,
136.50, 133.46, 130.58, 129.55, 128.09, 128.03, 126.29, 124.26, 122.35.
2-Phenyl-5-[1-(4-fluorophenyl)-meth-(Z)-ylidene]-3,5-dihydro-imidazol-
1
4-one (3d). Mp: found 274–276 ꢀC; H NMR (500 MHz, DMSO) d 12.11 (s, 1H),

3326
F. CHAVEZ ET AL.
8.40 (dd, J ¼ 5.9, 8.8, 2H), 8.17 (d, J ¼ 7.0, 2H), 7.64 (t, J ¼ 7.3, 1H), 7.60 (d, J ¼ 7.7,
2H), 7.32 (t, J ¼ 8.9, 2H), 7.05 (s, 1H); 13C NMR (126 MHz, DMSO) d 172.43,
164.30, 162.31, 161.42, 140.53, 134.88, 134.82, 133.01, 131.54, 129.46, 128.38,
127.85, 124.27, 116.40, 116.22. Anal. calcd. for C16H11FN2O: C, 72.17; H, 4.16; F,
7.13; O, 6.01; N, 10.52. Found: C, 71.66; H, 3.89; F, 7.37; O, 6.23; N, 10.43.
2-Phenyl-5-[1-(4-bromophenyl)-meth-(Z)-ylidene]-3,5-dihydro-imidazol-
1
4-one (3e). Mp: found 318–321 ꢀC; H NMR (500 MHz, DMSO) d 12.15 (s, 1H),
8.27 (d, J ¼ 8.6, 2H), 8.19 (d, J ¼ 7.1, 2H), 7.70 (d, J ¼ 8.6, 2H), 7.67 (t, J ¼ 7.9,
1H), 7.61 (t, J ¼ 7.4, 2H), 7.02 (s, 1H); 13C NMR (126 MHz, DMSO) d 172.37,
161.82, 141.40, 139.90, 134.23, 134.08, 133.17, 132.24, 129.50, 128.31, 127.95,
123.98. Anal. calcd. for C16H11BrN2O: C, 58.74; H, 3.39; Br, 24.42; O, 4.89; N,
8.56. Found: C, 58.37; H, 3.00; Br, 24.24; O, 5.03; N, 8.42.
2-Phenyl-5-[1-(4-methoxyphenyl)-meth-(Z)-ylidene]-3,5-dihydro-imidazol-
4-one (3f). Mp: found 292–294 ꢀC; lit. (289–290ꢀC)[3]; 1H NMR (500 MHz, DMSO)
d 12.02 (s, 1H), 8.31 (d, J ¼ 8.9, 2H), 8.17 (d, J ¼ 6.7, 2H), 7.63 (t, 1H), 7.60 (t,
J ¼ 7.1, 2H), 7.08 (d, J ¼ 9.0, 2H), 7.02 (s, 1H), 3.85 (s, 3H); 13C NMR (126 MHz,
DMSO) d 172.42, 161.34, 159.92, 139.02, 134.51, 132.67, 129.43, 128.62, 127.64,
127.60, 125.85, 114.89, 55.81.
2-Phenyl-5-[1-(4-methylphenyl)-meth-(Z)-ylidene]-3,5-dihydro-imidazol-
4-one (3g). Mp: found 302–304 ꢀC; lit. (288–289 ꢀC)[3]; 1H NMR (500 MHz,
DMSO) d 12.07 (s, 1H), 8.22 (d, J ¼ 8.2, 2H), 8.17 (d, J ¼ 6.9, 2H), 7.65 (t,
J ¼ 7.2, 1H), 7.60 (t, J ¼ 7.2, 2H), 7.31 (d, J ¼ 8.1, 2H), 7.01 (s, 1H), 2.37 (s, 3H);
13C NMR (126 MHz, DMSO) d 172.47, 160.73, 140.62, 140.21, 132.87, 132.57,
132.14, 129.91, 129.47, 128.51, 127.77, 125.77, 21.70.
2-Phenyl-5-[1-(4-nitrophenyl)-meth-(Z)-ylidene]-3,5-dihydro-imidazol-4-
1
one (3h). Mp: found 303–304 ꢀC; lit. (325–327 ꢀC)[7]; H NMR (500 MHz, DMSO)
d 12.29 (s, 1H), 8.56 (d, J ¼ 9.0, 2H), 8.30 (d, J ¼ 9.0, 2H), 8.23 (d, J ¼ 7.1, 2H), 7.69
(t, J ¼ 7.3, 1H), 7.63 (t, J ¼ 7.5, 2H), 7.11 (s, 1H); 13C NMR (126 MHz, DMSO) d
172.32, 163.70, 147.53, 143.49, 141.39, 133.63, 133.12, 129.53, 128.26, 128.02,
124.15, 121.97.
2-Phenyl-5-[1-thiophen-2-yl-meth-(Z)-ylidene]-3,5-dihydro-imidazol-4-
one (3i). Mp: found 310–311 ꢀC; lit. (291–292 ꢀC)[3]; 1H NMR (500 MHz, DMSO) d
12.07 (s, 1H), 8.17 (d, J ¼ 6.7, 2H), 7.92 (d, J ¼ 5.1, 1H), 7.74 (d, J ¼ 3.6, 1H), 7.66–
7.57 (m, 3H), 7.40 (s, 1H), 7.20 (t, 1H); 13C NMR (126 MHz, DMSO) d 171.55,
159.62, 138.54, 138.43, 135.27, 135.06, 132.80, 129.48, 128.44, 128.17, 127.70, 119.92.
2-Phenyl-5-[1-furan-2-yl-meth-(Z)-ylidene]-3,5-dihydro-imidazol-4-one
1
(3j). Mp: found 263–264 ꢀC; Lit. (266–267 ꢀC)[3]; H NMR (500 MHz, DMSO) d
12.09 (s, 1H), 8.17 (d, J ¼ 7.0, 2H), 7.98 (d, J ¼ 1.7, 1H), 7.64 (t, J ¼ 7.3, 1H), 7.58
(t, J ¼ 4.5, 11.5, 2H), 7.56 (t, 1H), 6.89 (s, 1H), 6.79 (d, J ¼ 3.5, 1H); 13C NMR
(126 MHz, DMSO) d 171.84, 160.49, 151.19, 146.83, 138.39, 132.89, 129.45,
128.40, 127.81, 118.71, 114.21, 112.69.
2-Phenyl-5-[1-biphenyl-4-yl-meth-(Z)-ylidene]-3,5-dihydro-imidazol-4-
1
one (3k). Mp: found 300–302 ꢀC; H NMR (500 MHz, DMSO) d 12.13 (s, 1H), 8.42

2,5-DISUBSTITUTED-3,5-DIHYDRO-IMIDAZOL-4-ONES
3327
(d, j ¼ 8.4, 2H), 8.21 (d, J¼ 6.9, 2H), 7.83 (d, J¼ 8.5, 2H), 7.77 (d, J¼ 7.2, 2H), 7.69–7.59
(m, 3H), 7.51 (t, J¼ 7.7, 2H), 7.41 (t, J¼ 7.3, 1H), 7.09 (s, 1H), 3.32 (s, 2H); 13C NMR
(126 MHz, DMSO) d 172.44, 161.26, 141.76, 140.94, 139.74, 134.04, 133.15, 133.02,
129.52, 129.51, 128.47, 128.45, 127.86, 127.38, 127.20, 125.06. Anal. Calcd. for
C22H16N2O: C, 81.46; H, 4.97; O, 4.93; N, 8.64. Found: C, 80.88; H, 4.70; O, 5.06; N, 8.59.
ACKNOWLEDGMENTS
We express sincere thanks to Stephan Chan for the valuable HPLC=MS data
and Dr. Jodie Brice for her useful comments.
REFERENCES
1. (a) Chan, G. W.; Mong, S.; Hemling, M. E.; Freyer, A. J.; Offen, P. H.; DeBrosse, C. W.;
Sarau, H. M.; Westley, J. W. New leukotriene B4 receptor antagonist: Leucettamine A and
related imidazole alkaloids from the marine sponge Leucetta microraphis. J. Nat. Prod.
1993, 56, 116–121; (b) Gadwood, R. C.; Kamdar, B. V.; Dubray, L. A. C.; Wolfe, M.
L.; Smoth, M. P.; Watt, W.; Mizsak, S. A.; Groppi, V. E. Synthesis and biological activity
of spirocyclic benzopyran imidazolone potassium channel openers. J. Med. Chem. 1993, 36,
1480–1487; (c) Cafieri, F.; Fattorusso, E.; Mangoni, A.; Taglialatela-Scafari, O. Dispaca-
mides, anti-histamine alkaloids from Caribbean Agelas sponges. Tetrahedron Lett. 1996,
37, 3587–3590.
2. (a) Kidwai, A. R.; Devasia, G. M. A new method for the synthesis of amino acids:
Synthesis of amino acids and their derivatives through 2,4-disubstituted 2-imidazolin-
5-ones. J. Org. Chem. 1962, 27, 4527–4531; (b) Shafi, P. M. Quantitative synthesis of
2-aryl-4-arylidene-2-imidazolin-5-ones. Curr. Sci. 1985, 54, 1231–1232; (c) Topuzyan, V.
O.; Arutyunyan, L. G.; Oganesyan. Derivatives of a,b-dehydro amino acids: III. Reaction
of 4-arylmethylidene-4,5-dihydro-1,3-oxazol-5-ones with hexamethyldisilazane. Russ.
J. Org. Chem. 2007, 43, 868–871; (d) Kochetkov, N. K.; Budovskii, E. I.; Khomutov,
R. M.; Karpeiskii, M. M. Cycloserine and related compounds. V: Cyclization of a-benza-
mido-b-arylacrylhydroxamic acids. Zh. Obshch. Khim. 1959, 29, 635–642; (e) Tiksari, A. M.;
Tripathy, P. K.; Mukerjee, A. K. Reactions of some 1,3-diaminonucleophiles with azlac-
tones. J. Chem. Soc. Perkin Trans. 1 1988, 1659–1662.
3. Fozooni, S.; Tikdari, A. M. Microwave-assisted graphite-support synthesis of imidazo-
lones. Catal. Lett. 2008, 120, 303–306.
4. Chavez, F.; Kennedy, N.; Rawalpally, T.; Cleary, T. Catalyzing the Erlenmeyer Plo¨chl
reaction: organic bases versus sodium acetate. Tetrahedron Lett. 2010, 51, 1533–1536.
5. (a) Khan, K. M.; Mughal, U. R.; Ambreen, N.; Samcreen; Perveen, S.; Choudhary, M. I.
Synthesis and leishmanicidal activity of 2,3,4-substituted-5-imidazolones. J. Enzyme Inhib.
Med. Chem. 2010, 25, 29–37; (b) Baldaniya;, B. B. Synthesis, characterization and biologi-
cal activity of 5-arylidene-3-(6,7-dichloro-1,3-benzothiazol-2-yl)-phenyl-3,5-dihydro-4H-
imidazol-4-ones. E-J. Chem. 2010, 7, 81–84; (c) Khan, K. M.; Mughal, U. R.; Khan, S.;
Khan, S.; Perveen, S.; Choudhary, M. I. Synthesis and antibacterial activity of 5-substituted
imidazolones. Lett. Drug Design Discov. 2009, 6, 66–77; (d) Saravanan, S.; Selvan, P. S.;
Gopal, N.; Gupta, J. K.; De, B. Synthesis and antibacterial activity of some imidazole-5-(4-
H)-one derivatives. Arch. Pharm. Chem. Life Sci. 2005, 338, 488–492.
6. Devasia, G. M. A new method for the synthesis of unsaturated 2,4-disubstituted
2-imidazolin-5-ones. Tetrahedron Lett. 1976, 7, 571–572.
7. Devasia, G. M.; Shafi, P. M. A convenient synthesis of unsaturated 2,4-disubstituted
2-imidazolin-5-ones. Indian J. of Chem., Sect. B 1981, 20B, 657–660.