Green and Sustainable Chemistry, 2011, 1, 12-18
doi:10.4236/gsc.2011.11003 Published Online February 2011 (
Copyright © 2011 SciRes. GSC
The Synergy of Combined Use of DMSO and Bronsted
Acid (Ionic Liquid) as a Catalyst
——Part I: Efficient Niementowski synthesis of modified quinazolinones
Muthu Kumaradoss Kathiravan1, Rajeshwar Rajendra Jalnapurkar1, Aparna Surendra Chothe1,
Trupti Sameer Chitre1, Riyaj Shaukat Tamboli2, Kumar V. Srinivasan*3
1Department of Pharmaceutical Chemistry, AISSMS College of Pharmacy, Near RTO Office, Pune, India
2Pharmacy Department, The Maharaja Sayajirao University of Baroda, India
3Division of Orga ni c C hemi st ry, National Chemical Laboratory, Pune, India
Received January 19, 2011; revised February 20, 2011; accepted February 24, 2011
A new rapid and versatile approach using Ionic Liquid/DMSO as a chemical reagent for the synthesis of
fused heterocyclic compounds in a highly efficient way is described. This method offers the advantages of
proceeding in neutral conditions, giving high to excellent isolated yields (83-92%) for Niementowski synthe-
sis with easy workup procedure. The inherent Bronsted acidity of ionic liquid and high polarity of both IL
and DMSO resulted in a significant enhancement in the reaction rate.
Keywords: Ionic Liquids, DMSO, Niementowski
1. Introduction
Rutaecarpine type alkaloids constitute an important class
of indolopyridoquinazolinone heterocycles, which be-
long to the subgroup of quinazoline type alkaloid, be-
longing to Rutaceae family [1]. Rutaecarpine (Figure 1)
shows a variety of pharmacological activities including
antithrombotic [2], vasorelaxant [3], cyclooxygenase
(CoX-2) inhibitor [4,5], thermoregulatory, anti-obesity
[6], as well as effects on the cardiovascular and endocrine
systems [7]. The progress in the studies of rutaecarpine
has been reviewed [8]. Recently numerous thiophene
analogues of rutaecarpine [9] as well as quinazoline have
shown good anticancer activity [10], analgesic [11],
anti-inflammatory [12-14] as well as antiparkinsonims
activity [15]. Bioisosterism is a strategy of medicinal
chemistry for the rational design of new drug, applied
with a lead compound as a special process of molecular
modification [16]. Purine bases and their bioisoteric
analogs were widely used as building block in combina-
torial chemistry. The bioisoteres of purine bases such as
thienopyrimidine and pyridopyrimidine possess wide
range of biological activity such as PDE inhibitory activ-
ity, antiparkinsonism, CNS depressant, analgesic, anti-
inflammatory [17-19] etc.
Since Niementowski’s preparation of 4(3H)-quina-
zolinone by fusing anthranilic acid with formamide [20],
several methods aimed toward the synthesis of modified
quinazolinones have been pursued [21,22]. Recently a
series of 1,3,10,12-tetrasubstituted-8H-pyrido-[2',3':4,5]-
pyrimido[6,1-b]quinazolin-8-ones [23] and tetracyclic
[6,1-b]-quinazolin-7-ones [24] has been reported by
Laddha et al. However the reaction did not go to comple-
tion in our hands as reported by the authors. Each of these
methods has one or more of the following drawbacks. For
instance, the use of expensive and toxic reagents, harsh
reaction conditions, refluxing for a prolonged period of
time, tedious work-ups etc. In addition, the known meth-
ods made use of volatile organic solvents, leading to com-
plex isolation and recovery procedures. Therefore, we
sought to develop a more efficient and convenient method
that avoids these drawbacks and could be used on both
laboratory as well as industrial scale.
Ionic Liquid (ILs) have been widely recognized as an
efficient synthetic tool and its benefit has been well
documented. Ionic liquids have been touted as replace-
ments for traditional molecular solvents in synthesis be-
cause of most of them are nonvolatility, nonflammability,
their stability and ease of recyclability [25]. An extensive
literature describing the diversity of ionic liquids are
available [26]. Recently ionic liquid has been designed
specifically for nucleophilic aromatic substitutions [27].
Very recently we have investigated the synergy of
the combined use of ionic liquid and DMSO in the pro-
portion 0.1:1 to synthesize a variety of esters in re-
markably short reaction times from acyl or alkyl halides
by their reaction with sodium carboxylates in the above
-mentioned mixed solvent medium in the absence of
any added catalyst under ambient conditions [28,29].
Till now there is no reported method for Niemen-
towski’s synthesis using ionic liquids to the best of our
knowledge. We aimed to modify the procedure reported
till now using ionic liquids which can be applicable not
only for fused quinazoline but to a wide range of fused
heterocycles such as substituted thienopyrimidine, pyri-
dothienopyrimidines, triazinoquinazolines as well as
In continuation of our ongoing work on condensed
thienopyrimidines and quinazolines [30,31], we herein
report the fused heterocyclic derivatives of thieno-
pyrimidine and quinazoline as divalent and ring
equivalent isosteres of Rutaecarpine. Hence a series of
novel heterocyclic compounds belonging to thieno-
pyrimidine fused with quinazoline, substituted thio-
phene, pyridothiophene and quinazoline fused with
substituted thiophene, pyridothiophene, quinazoline
were synthesized using ionic liquid and DMSO. We
initiated this study with the goal of expanding the effi-
cacy and efficiency of the methodologies developed by
us using ionic liquids for the synthesis of fused het-
erocycles [32].
2. Result and Discussion
The starting material employed thiophene o-aminoesters,
their subsequent cyclization with formamide and chlori-
nation were done as per our earlier reported method [32].
The latter reaction is either carried out in microwave or by
classical heating using polyphosphoric acid. The next step
involves the reaction of anthranilic acid and condensed
4-chloro-pyrimidine to give the desired products. It is
assumed that formation of products requires an acyl sub-
stitution between the pyrimidine nitrogen and the car-
boxylic acid group.
Figure 1. Structure of rutaecarpine.
All the present synthetic methodology for condensa-
tion reaction have one or the other draw back of lengthy
reaction time, high temperature and in many synthesis
the use of Volatile Organic Compounds (VOC’s) such as
tetrahydrofuran (Scheme 1) which are detrimental to the
environment and solvents that need to be recovered and
recycled completely adding to the economics of the
Our research work devoted to the combined use of
ionic liquid and DMSO in 0.1:1 proportion, we extended
the investigation of this system towards the present syn-
thesis. We have exploited this type of reaction by em-
ploying cyclic iminochlorides in the synthesis of fused
heterocyclic in an attempt to increase the rate of reaction
using ionic liquid.
The reaction was initially carried out in DMSO and
Ionic liquids [bbim]+ Br- independently. However, in
DMSO there was no reaction but in ionic liquid the reac-
tion went to completion in 10 hrs. Using the above sol-
vent mixture conditions DMSO/IL (1:0.1 proportion), the
reaction was completed in just 45-60 min (Scheme 2).
The bronsted acidic IL was responsible for promotion of
the reaction. We have successfully done first cyclization
step using DMSO/IL in 45-60 minutes (Table 1) with
better yields and purity. However the conventional heat-
ing method of cyclization required 8-24 hr for each reac-
tion. It was observed that under similar conditions, the
substrate containing o-amino acids underwent condensa-
tion with cyclic iminochlorides at a faster rate when
compared to o-amino esters. Solvents with hydrogen-
bond accepting properties can interact with the protons
of the acid, increasing the electron density on the nitro-
gen atom and therefore its nucleophilic character. This
increase has been shown when DMSO is used as the
solvent. Ionic liquids as bronsted acid can bond with
sulphonyl oxygen of DMSO and give rise to dimsyl ion.
Dimsyl ion can then interact with amine hydrogen of
anthranilic acid as well as thiophenes resulting in naked
-NH ions. The naked ion is highly reactive giving rise to
the observed reaction.
Thus the use of ionic liquid in synergy with DMSO
was found to accelerate and significantly improved the
yield and reduced the time of the reaction. The synergy
of combined use of IL and DMSO is evident from the
observation that the reaction did not proceed at all either
in DMSO or in [bbim]+Br- individually under similar
Scheme 1
Copyright © 2011 SciRes. GSC
Copyright © 2011 SciRes. GSC
Scheme 2
conditions. This method offers a route to free carboxylic
acid as well as ester condensation. Compared to the re-
ported methods, our method is convenient, safe, and can
be performed under ambient conditions with easy isola-
tion procedures by drowning the reaction mixture into
ice water. The IL could be recovered from the aqueous
filtrate by distillation under reduced pressure. Our par-
ticular important achievement is with respect to reaction
in the last step which took much shorter reaction time
than hitherto reported. The process is amenable to scale
up and can be gainfully employed to synthesize a library
of condensed thienopyrimidines as well as quinazoline
analogues. The overall yield is better than those reported
so far.
3. Conclusion
We have described a new, rapid and a versatile approach
using DMSO and ionic liquid as a chemical catalysts for
the synthesis of fused heterocyclic compounds in a
highly efficient way. Additional work is in progress to
obtain different types of fused heterocycles with various
biological activities.
4. Experimental
The IL [bbim]+Br- is synthesized as per the procedure
reported by us [29]. Typical procedure for the reaction of
cyclic iminochlorides with o-amino acids/esters by the
combination of ionic liquid and DMSO. 3a-j
A mixture of 4-chlorothieno[2,3-d]pyrimidine (0.044
mol), amino acid/ester (0.045 mol) in [bbim]+Br - and
DMSO in 0.1:1 (0.5 g:5 g) proportions was heated at
100oC on oil bath for 45-60 minutes. The progress of the
reaction was monitored by TLC. The reaction mixture
was quenched in ice cold water (30 ml), precipitated
solid was filtered, washed with cold water and air-dried.
The mixture of IL and DMSO was recovered from the
aqueous filtrate by subjecting it to distillation under re-
duced pressure. The product was pure enough (single
spot on TLC) for all practical purposes. However, for
characterization purposes it was further purified by col-
umn chromatography (30% ethylacetate: n-hexane).
do6,1-b]quinazolin-9 -one
3a: δH (400 MHz, CDCl3), 1.83 (4H, m, CH2), 2.63
(2H, t, CH2), 2.82 (2H, t, CH2), 7.39 (4H, m, CH), 7.99
(1H, s, CH); νmax (neat)/cm1: 1692 (C=O), 1591 (C=C),
1546 (C=N), 3057 (C-H aromatic stretch); m/z 307.2
(M+); Calcd. for C17H13N3OS: C, 66.43; H, 4.46; N,
13.45; Found: C, 66.3; H, 4.2; N, 13.7.
3b: δH (400 MHz, CDCl3), 1.61 (8H, m, CH2), 1.87
(4H, t, CH2), 2.89 (2H, t, CH2), 2.03 (2H, t, CH2), 7.93
(1H, s, CH); νmax (neat)/cm1: 1562 (C=N), 1680 (C=O),
1588 (C=C), 3040 (C-H aromatic stretch); m/z 367.4
(M+); Anal. Calcd. for C19H17N3OS2: C, 62.10; H, 4.66;
N, 11.43; Found: C, 62.0; H, 4.7; N, 11.4.
3c: δH (400 MHz, CDCl3), 1.84 (4H, m, CH2), 2.39 (3H,
s, CH3), 2.47 (3H, s, CH3), 2.78 (2H, t, CH2), 2.96 (2H, t,
CH2), 7.80 (1H, s, CH); νmax (neat)/cm1: 1684 (C=O),
1591 (C=C), 1548 (C=N), 3042 (C-H aromatic stretch),
2933 (C-H aliphatic stretch); m/z 343.2 (M+); Anal. Calcd.
for C17H17N3OS2: C, 59.45; H, 4.99; N, 12.23.
3d: δH (400 MHz, CDCl3), 1.88 (4H, m, CH2), 2.57
(3H, s, CH3); 2.71 (3H, s, CH3), 2.63 (2H, t, CH2), 2.82
(2H, t, CH2), 6.92 (1H, s, CH), 7.95 (1H, s, CH); νmax
(neat)/cm1: 1682 (C=O), 1592 (C=C), 1553 (C=N), 3038
(C-H aromatic stretch), 2936 (C-H aliphatic stretch); m/z
394.2 (M+); Anal. Calcd. for C20H18N4OS2: C, 60.89; H,
.60; N, 14.20; Found: C, 60.5; H, 5.1; N, 14.6. 4
Copyright © 2011 SciRes. GSC
Table 1. Ionic liquid and DMSO promoted synthe sis of some novel fused he terocycles (3a-3j).
Ionic liquids
Sr. No Structure Yielda
(%) Mp
(oC) Time
92 212-214 45
85 233-235 60
83 222-224 60
89 282-283 60
91 205-208 45
85 266-268 60
88 245-248 60
90 269-273 60
89 285-288 45
93 297-299 60
3e: δH (400 MHz, CDCl3), 7.07-7.87 (8H, m, CH),
7.89 (1H, s, CH). νmax (neat)/cm1: 1682 (C=O), 1608
(C=C), 3026 (C-H aromatic stretch), 1562 (C=N). m/z
247.1 (M+). Anal. Calcd. for C15H9N3O: C, 72.87; H,
3.67. Found: C, 72.9; H, 3.4; N, 17.2.
3f: δH (400 MHz, CDCl3), 1.81 (4H, m, CH2), 2.68
(2H, t, CH2), 2.86 (2H, t, CH2), 7.33 (4H, m, CH), 7.98
(1H, s, CH); νmax (neat)/cm1: 1706 (C=O), 1605 (C=C),
3007 (C-H aromatic stretch), 1530 (C=N); m/z 307.2
(M+); Anal. Calcd. for C17H13N3OS: C, 66.43; H, 4.26; N,
13.67. Found: C, 66.6; H, 4.5; N, 13.2.
3g: δH (400 MHz, CDCl3), 2.40 (3H, s, CH3), 2.48
(3H, s, CH3), 7.33 (4H, m, CH), 7.95 (1H, s, CH); νmax
(neat)/cm1: 1684 (C=O), 1598 (C=C), 1548 (C=N),
3019 (C-H aromatic stretch), 2940 (C-H aliphatic
stretch); m/z 281.2 (M+). Anal. Calcd. for C15H11N3OS: C,
64.04; H, 3.94; N, 14.94. Found: C, 65.2; H, 3.8; N, 15.1.
10,12-Dimethy-8-thia-5,6a,9,13- tetraaza-indeno(2,1-b)-
3h: δH (400 MHz, CDCl3), 1H NMR (400 MHz,
CDCl3): δ, 2.61 (3H, s, CH3); 2.74 (3H, s, CH3), 6.68
(1H, s, CH), 7.28 (4H, m, CH), 7.86 (1H, s, CH); νmax
(neat)/cm1: 1674 (C=O), 1592 (C=C), 1542 (C=N),
2938 (C-H aliphatic stretch); m/z 307.2 (M+); Anal.
Calcd. for C18H12N4OS: C, 65.04; H, 3.64; N, 16.86,
Found: C, 64.8; H, 3.8; N, 16.3.
1,2-Dimethyl-7H-thieno[2',3 ':4 ,5]pyrimido[6,1-b]qui-
3i: δH (400 MHz, CDCl3), 2.44 (3H, s, CH3), 2.51
Copyright © 2011 SciRes. GSC
(3H, s, CH3), 7.26 (4H, m, CH), 7.88 (1H, s, CH); νmax
(neat)/cm1: 1695 (C=O), 1601 (C=C), 1542 (C=N),
3034 (C-H aromatic stretch), 2938 (C-H aliphatic
stretch); m/z 281.2 (M+); Anal. Calcd. for C15H11N3OS: C,
64.04; H, 3.94; N, 14.94. Found: C, 64.1; H, 4.2; N, 14.7.
3j: δH (400 MHz, CDCl3) δ, 2.41 (3H, s, CH3), 2.48
(3H, s, CH3), 2.65 (3H, s, CH3); 2.72 (3H, s, CH3), 6.42
(1H, s, CH), 7.94 (1H, s, CH); νmax (neat)/cm1: 1690
(C=O), 1610 (C=C), 1554 (C=N), 3018 (C-H aromatic
stretch), 2938 (C-H aliphatic stretch); m/z 366.4 (M+).
Anal. Calcd. for C18H14N4OS2: C, 58.99; H, 3.85; N,
15.29. Found: C, 59.3; H, 3.6; N, 15.4.
5. Acknowledgments
We are grateful to Dr. Mrs. A. R. Madgulkar, Principal,
AISSM’s College of Pharmacy, Pune, for providing us
with the necessary financial support and infrastructure
for carrying out this work.
6. References
[1] Y. Asahina and K. Kashiwaki, “Chemical Constituents of
the Fruits of Evodia Rutaecarpa,” Yakugaku Zasshi, Vol.
405, 1915, pp. 1273-1293.
[2] L. R. Sheu, W. C. Hung, Y. M. Lee and M. H. Yen,
“Mechanism of Inhibition of Platelet Aggregation by Ru-
taecarpine, an Alkaloid Isolated from Evodia Rutae-
carpa,” European Journal of Pharmacology, Vol. 318,
1996, pp. 469-475.
[3] W. F. Chiou, J. F. Liao and C. F. Chen, “Comparative
Study on Vasodilatory Effects of Three Quinazoline Al-
kaloids Isolated from Evodia Rutaecarpa,” Journal of
Natural Products, Vol. 59, 1996, pp. 374-378.
[4] S. Hibino and T. Choshi, “Simple Indole Alkaloids and
Those with a Nonrearranged Monoterpenoid Unit,”
Natural Product Reports, Vol. 18, 2001, pp. 66-87.
[5] T. C. Moon, M. Murakami, I. Kudo, K. H. Son, H. P.
Kim, S. S. Kang and H. W. Chang, “A New Class of
COX-2 Inhibitor, Rutaecarpine from Evodia Rutaecarpa,”
Inflammation Research, Vol. 48, 1999, pp. 621-625.
[6] H. K. Raymond,Sur la Ceto-yobyrine,” Comptes Rendus,
Vol. 226, 1948, pp. 1379-1381.
[7] J. Tames, G. Bujtas, K. Horvath-Dora and O. Clauder,
“Alkaloids Containing the Indolo [2,3-c]-quinazolino-
[3,2-a] Pyridine Skeleton, IV. The Mass Spectra of
Rutaecarpine, Evodiamine and 3,14-Dihydrorutaecarpine,”
Acta Chimica Academiae Scientiarum Hungaricae, Vol.
89, 1976, pp. 85-89.
[8] S. H. Lee, J. K Son, B. S. Jeong, T. C. Jeong, W. C.
Hyeon, E. S. Lee and Y. Jahng, “Progress in the Studies
on Rutaecarpine,” Molecules, Vol. 13, No. 2, 2008, pp.
272-300. doi:10.3390/molecules13020272
[9] A. Hamid, A. Elomrib and A. Daich, “Expedious and
Practical Synthesis of the Bioactive Alkaloids
Rutaecarpine, Euxylophoricine A, Deoxyvasicinone and
Their Heterocyclic Homologues,” Tetrahedron Letters,
Vol. 47, 2006, pp. 1777-1781.
[10] L. M. Yang, S. J Lin, L. C Lin and Y. H. Kuo, “Antitumor
Agents. 2. Synthesis and Cytotoxic Evaluation of
10-bromorutaecarpine,” Chinese Pharmaceutical Journal,
Vol. 51, 1999, pp. 219-225.
[11] H. Miyamatsn, S. Ueno, M. Shimizu, J. Hosono, M.
Tomari, K. Seida, T. Suzuki and J. Wada, “New
Nonsteroidal Antiinflammatory Agent. 3. Analogs of
2-substituted 5-benzothiazoleacetic Acids and Their De-
rivatives,” Journal of Medicinal Chemistry, Vol. 17, 1974,
pp. 491-496. doi:10.1021/jm00251a004
[12] E. Bansal, T. Ram, S. Sharma, M. Tyagi, A. P. Rani, K.
Bajaj, R. Tyagi, B. Goel, V. K. Srivastava, J. N. Gurtu
and A. Kumar,Thiazolidinyl-triazinoquinazolines as
Potent Anti-inflammatory Agents,” Indian Journal of
Chemistry, Vol. 40B, 2001, p. 307.
[13] K. Okumura, T. Oine, Y. Yamada, G. Hayashi, M. Nakama
and T. Nose, “4-Oxo-1,2,3,4-tetrahydroquinazolines. II.
Synthesis of 1-Alkyl- and 1-[2,(Distributed amino) ethyl]-
Journal of Med ic inal Chemistr y, Vol. 11, 1968, pp. 788-792.
[14] K. Ozaki, Y. Yamada, T. Oine, T. Ishizuka and Y.
Iwasawa, “Studies on 4(1H)-Quinazolinones. 5. Synthesis
and Antiinflammatory Activity of 4(1H)-Quinazolinone
Derivatives,” Journal of Medicinal Chemistry, Vol. 28,
1985, pp. 568-576. doi:10.1021/jm50001a006
[15] H. Itahana, T. Kamikubo, E. Nozawa, H. Kaku, M.
Okada, T. Toya and A. Nakamura, PCT International
Application, 2002, WO 2002062803; Chemical Abstracts,
Vol. 137, 2002, p. 169542.
[16] L. M. Lima and E. J. Barreiro, “Bioisosterism: A Useful
Strategy for Molecular Modification and Drug Design,”
Current Medicinal Chemistry, Vol. 12, 2005, pp. 23-49.
[17] S. S. Laddha and S. P. Bhatnagar, “A New Therapeutic
Approach in Parkinson’s Disease: Some Novel Quinazoline
Derivatives as Dual Selective Phosphodiesterase 1
Inhibitors and Anti-inflammatory Agents,” Bioorganic &
Medicinal Chemistry, Vol. 17, 2009, pp. 6796-6802.
[18] M. S. Manhas, S. D. Sharma and S. G. Sharma, “Hetero-
cyclic Compounds. 4. Synthesis and Antiinflammatory
Activity of Some Substituted Thienopyrimidones,” Jour-
nal of Medicinal Chemistry, Vol. 15, 1972, pp. 106-107.
[19] M. J. Kulshreshtha, S. Bhatt, P. Madhuri and N. M.
Khanna, “Synthesis of 2-methyl, 3-aryl or arylalkyl 5,
6-dimethyl or Polymethylene Thieno [2,3-d]-Pyrimidine-
4-ones,” Journal of the Indian Chemical Society, Vol. 58,
No. 10, 1981, p. 982.
[20] S. J. von Niementowski, “Synthesen von Chinazolinver-
bindungen,” Journal für Praktische Chemie, Vol. 51,
1895, pp. 564-572.
[21] D. J. Brown, Quinazolines, Supplement I. Interscience
Publishers, New York, 1996, pp. 1-150. W. L. F. Ar-
marego, In: Fused Pyrimidines; D. J. Brown, Ed.; Inter-
science Publishers, New York, 1967, pp. 89-218.
Copyright © 2011 SciRes. GSC
Copyright © 2011 SciRes. GSC
[22] E. S. Lee, J. G. Park and Y. Jahng, “A Facile Synthesis of
Simple Alkaloids-Synthesis of 2,3-polymethylene-4(3H)-
quinazolinones and Related Alkaloids,” Tetrahedron Let-
ters, Vol. 44, 2003, pp. 1883-1886.
[23] S. S. Laddha and S. P. Bhatnagar, “Efficient Niementowski
Synthesis of Novel 1,3,10,12-tetra- substituted-8H-pyrido-
[2',3':4,5]py rimido[6,1-b]quinazolin-8-ones,” Arkivoc, Vol.
(xvi), 2007, pp. 1-11.
[24] S. S. Laddha and S. P Bhatnagar, “Efficient Niementowski
Synthesis of Novel Derivatives of 1,2,9,11-tetrasub-
one,” Arkivoc, Vol. (xvii), 2008, pp. 212-220.
[25] (a) T. Welton, “Room-Temperature Ionic Liquids. Sol-
vents for Synthesis and Catalysis,” Chemical Reviews,
Vol. 99, 1999, pp. 2071-2083. doi:10.1021/cr980032t
(b) P. Wasserscheid and W. Keim, “Ionic Liquids-New
‘Solutions’ for Transition Metal Catalysis,” Ange-
wandte Chemie International Edition, Vol. 39, 2000, pp.
3772-3789. (c) J. Dupont, R. F. de Souza and P. A. Z.
Suarez, “Ionic Liquid (Molten Salt) Phase Or-
ganometallic Catalysis,” Chemical Reviews, Vol. 102,
2002, pp. 3667-3692. (d) N. Jain, A. Kumar, S. Chau-
han and S. M. S. Chausan, “Chemical and Biochemical
Transformations in Ionic Liquids,” Tetrahedron, Vol.
61, 2005, pp. 1015-1060. doi:10.1016/j.tet.2004.10.070
[26] John S. Wilkes, In: P. Wasserscheid and T. Welton,
Eds., Ionic Liquids in Synthesis, 2nd Edition,
VCH-Wiley, Weinheim, 2007.
[27] I. Newington, J. M. Perez-Arlandis and T. Welton, “Ionic
Liquids as Designer Solvents for Nucleophilic Aromatic
Substitutions,” Organic Letters, Vol. 9, No. 25, 2007, pp.
[28] S. S. Palimkar, S. A. Siddiqui, T. Daniel, R. J. Lahoti and
K. V. Srinivasan, “Ionic Liquid-Promoted Regiospecific
Friedlander Annulation: Novel Synthesis of Quinolines
and Fused Polycyclic Quinolines,” Journal of Organic
Chemistry, Vol. 68, 2003, pp. 9371-9378.
[29] S. N. Dighe, K. S. Jain and K. V. Srinivasan, “A Novel
Synthesis of 1-aryl Tetrazoles Promoted by Employing
the Synergy of the Combined Use of DMSO and an Ionic
Liquid as the Solvent System at Ambient Temperature,”
Tetrahedron Letters, Vol. 50, 2009, pp. 6139-6142.
[30] M. K. Kathiravan, C. J. Shishoo, S. K. Roy, K. R.
Mahadik, S. S. Kadam and K. S. Jain, “Synthesis and An-
tihyperlipidemic Activity of Some Novel Condensed 2-
chloroalkyl-4-chloro/hydroxy-5,6-disubstituted Pyrimidi-
nes,” Arzneimittel-Forschung/Drug Research, Vol. 57,
No. 9, 2007, pp. 599-604.
[31] M. S. Phoujdar, M. K. Kathiravan, J. B. Bariwal, A. K.
Shah and K. S. Jain, “Microwave-based Synthesis of
Novel Thienopyrimidine Bioisosteres of Gefitinib,”
Tetrahedron Letters, Vol. 49, 2008, pp. 1269-1273.
[32] K. S. Jain, J. B. Bariwal, M. S. Phoujdar, R. D. Amrutkar,
M. K. Munde, R. S. Tamboli, S. A. Khedkar, R. H.
Khiste, N. C. Vidyasagar, V. V. Dabholkar and M. K.
Kathiravan, “A Novel Microwave-assisted Green Synthesis
of Condensed 2-substituted-pyrimidin-4(3H)-ones under
Solvent-free Conditions,” Journal of Heterocyclic
Chemistry, Vol. 46, No. 2, 2009, pp. 178-185.