Comparitive Study of Microwave and Conventional Synthesis

Int. J. Pharm. Sci. Rev. Res.
, 15(1), 2012; nᵒ 04, 15-22 ISSN 0976 – 044X
Review Article
COMPARATIVE STUDY OF MICROWAVE AND CONVENTIONAL SYNTHESIS

AND PHARMACOLOGICAL ACTIVITY OF PYRIMIDINES: A REVIEW
1 2 3 1
Chandak Shilpa , Sharma Dipak , Sharma Vimukta , Dubey Arti
1
Department of Engineering Chemistry, VITS, Indore, MP, India.
2
Department of Chemical Sciences, Maharaja Ranjit Singh College of Professional Sciences, Indore, MP, India.
3
Principal, B.M. College of Pharmacy, Indore, MP, India.
Accepted on: 02-03-2012; Finalized on: 30-06-2012.

ABSTRACT
Pyrimidine derivatives play a vital role in many biological processes. Pyrimidine ring system is being present in nucleic acids, several
vitamins, coenzymes, uric acid and some marine microorganisms (e.g. Sponge). The nitrogen heterocycles in general and pyrimidines
in particular are found in several biologically active natural products and depict considerable therapeutic potential. Chalcone
derivatives have been prepared by condensation of various substituted aryl aldehydes and acetophenone in alkaline ethanol, while
pyrimidine-2-one derivatives have been prepared by the combination of chalcones and urea under conventional and ultrasonic
conditions. The compound substituted ethyl-1,2,3,6-tetrahydro-4-methyl-2-oxo/thioxo-6-phenyl-1-(4,6-diphenyl-1Himidazolyl-2-
yl)pyrimidine-5-carboxylates have been synthesized by condensing substituted Benzil and enthyl-1-formyl-1,2,3,6-tetrahydro-4-
methyl-6-phenyl-2-oxo/thioxo-pyrimidine-5-carboxylates in the presence of ammonium acetate were dissolved in glacial acetic. The
quinolinylpyrimidine derivatives were prepared by the condensation of quinolinyl chalcones with urea (or thiourea) under basic
conditions by using both conventional and microwave heating. A beneficial ultrasound effect was observed and high yields of the
products were obtained. Characterization and structural elucidation of the products have been done on the basis of chemical,
analytical and spectral analysis. The newly prepared pyrimidine derivatives were screened for antimicrobial activities.
Keywords: Pyrimidine derivatives, Chalcone derivatives, Quinolinylpyrimidine, Antimicrobial, Biginelli compounds,
chemotherapeutic agents.
INTRODUCTION hepatitis B virus replication inhibitors and depict a variety

of other biological effects. Although a large number of
Heterocyclic rings have played an important role in
DHPM derivatives have been prepared in a single-pot
medicinal chemistry, serving as key templates central to
Biginelli multi component reaction10 (MCR) and its
the development of numerous important therapeutic
variants10, very useful and convincing structural variability
agents1. Chalcone derivatives are important starting
of these interesting heterocycles have been achieved
materials for the synthesis of different classes of
through chemical functionalization of all the six positions
heterocyclic compounds such as pyrazolines, thiophenes
around the DHPM core10. The 4-aryl-1, 2, 3, 4-
and pyrimidines, etc. most of these compounds are highly
2 tetrahydropyrimidines has been given the name Biginelli
bioactive and are widely used in pharmaceutics .
compounds. The main interest in Biginelli compounds,
Pyrimidine derivatives have found application in a wide however, is due to the strong antihypertensive activity
8
range of medicinal chemistry because of their diverse exhibited by certain derivatives .
3 3
biological activities, such as anti allergic , antitumor ,
Pyrimidines and fused pyrimidines, being an integral part
antipyretic3 anti-inflammatory3, antiparasitic4, anti
5 5 5 5 of DNA and RNA, play an essential role in several
fungal , antimalarial , antibacterial , antimycotic ,
6 1 7 7 biological processes and have considerable
anticancer , antimicrobial , anti HSV , anti-convulsion
7 pharmacological importance, particularly, the pyrimidine
and anti-viral also these compounds are considered to be
ring can be found in nucleoside, antibiotics,
important for synthetic drugs (e.g. Barbituric acid
Cardiovascular as well as agrochemical and veterinarian
derivatives)8, chemotherapeutic agents (e.g.
products. Pyrimidines present an interesting group of
Sulfadiazine)8 and agricultural chemicals. During a
compounds many of which possess wide-spread
screening effort for antiviral agents, we found that multi
pharmacological properties such as antidepressant,
functionalized tetrahydropyrimidines derivatives bearing
anticon-vulsant activities. Heterocyclic compounds have
bulky C-2 alkyl substituents depict cytostatic activity and
received considerable attention owing to their variety of
inhibit proliferation of murine leukemia, murine
biological activities, especially as inhibitors of PDE5
mammary carcinoma, human T-lymphocyte and human
extracted from human platelets, HIV-1 reverse
cervix carcinoma cells9, 3, 4-Dihydropyrimidin-2-(1H)-ones
transcriptase, human EPK2. Also heterocyclic nitrogen
(DHPMs) and their appropriately functionalized
compounds are indispensable structural units for
derivatives have interesting pharmacological profiles10.
medicinal chemists and used as antibiotics, anthelmintics.
These are potent antihypertensive agents, mitotic kinesin
anti-depressant and anti-inflammatory11.
inhibitors, a1a-adrenergic receptor antagonists, or
International Journal of Pharmaceutical Sciences Review and Research Page 15
Available online at www.globalresearchonline.net
Int. J. Pharm. Sci. Rev. Res., 15(1), 2012; nᵒ 04, 15-22 ISSN 0976 – 044X
Table 1: Pharmacological activities of Pyrimidines 17 N N Antimicrobial

Ref. Pharmacological NH
activity
Structure N S
no. Activity
O O
8 Antimicrobial S N
HN NH CH3
CH O
activity
O
18 Anti-
3 CH 3
CH 3 O
N HN N inflammatory
OR
N NH 2
activity
NC
F
H 3C
12 Antifungal and
Ph Antibacterial
N
activity 19 Antibacterial and
C 2 H 5 OOC
N
N
Ph
O
Antifungal
H 3C N O
H activity
H HN N
O Cl
2 Antibacterial
O
OH N NH activity 20 N OH Antioxidant and
O Antibacterial
N
activity
N O Cl N
Et HS N
11 CH3 Analgesic activity OCH 3

COOEt
N
21 N Antileishmanial
N SH CN activity
N
N
H3CS N
CH3
CH3
11 Anti- N
COOEt
N inflammatory 22 C 6H 5 H Antibacterial and
activity Ph N N S Antifungal
N NHph
activity
N
N C6 H5
CH3
Ph
11 CH3 Anti- O
N
OH
parkinsonism 23 CN Antibacterial and
Ph N Antifungal
activity
N S CONHph activity
NH
Ph
N
C6H 5 Ph
CH3
O
13 Antibacterial and
CN Antibacterial PREPARATION METHODS
HN
activity The chalcones were prepared by the Claisen Schmidt
S N
H condensation using both conventional as well as
N ultrasonic assisted methods (Scheme I) 3.
H
14 O Antimicrobial OH CH3
O
OH O
C CH3
activity CH3
+
HN N O Cl N O Cl
CN OCH Et Et
N 3
Scheme I
S N
H
A series of quinolinylpyrimidine derivatives have been
15 CN Antibacterial and prepared by using both conventional and microwave
Ph N antifungal induced heating. The compounds were prepared by the
activity condensation of quinolinyl chalcones with urea (or
NH
Ph
thiourea) in basic media under prolonged refluxing
C 6H 5 Ph
O conditions or under microwave irradiations (Scheme II)3.
16 NHSO CH 3
Antimicrobial
2
N
activity O
N
N N N NH
OH O OH
O NH2
+ H2N
O
N O Cl N O Cl
Et Et
Scheme II

Table 2: Comparison between microwave-assisted and conventional method of synthesis in terms of yield and time
Microwave Irradiation Conventional Heating
Structure Ref. No.
Time (min) Yield (%) Time (hr.) Yield (%)
HN NH
24 82 6.5 65 3
O
CH3
22 78 6 55 3
HN NH
S
H3C
3
21 80 6 54
HN NH
O
H3C
HN NH
24 76 6 58 3
O
OCH 3
28 78 5.5 60 3
HN NH
O
H3CO
25 75 5.5 61 3
HN NH
O
H3CO OCH3
22 73 5 65 3
HN NH
O
(Me)2N
29 75 5.5 55 3
HN NH
Ph
N
C2 H5COO
N
Ph 8 79 12 64 3
N
H
H3 C N O
H
Ph
NO 2N
C 2H 5COO
N
Ph 8 78 12 64 3
N
H
H 3C N O
H
Cl
Ph
N 3
C2H5COO Ph
8 69 12 62
N N
H
H3C N O
H
OCH 3
Ph
N
C 2H 5COO Ph
8 72 12 65 3
N N
H
H3C N O
H
Ph
N
C 2H 5COO
N
Ph 8 78 12 65 3
N
H
H 3C N S
H
Cl
Ph
N 3
C2 H5COO Ph
8 75 12 63
N N
H
H3 C N S
H


Structure Ref. No.
Ph
N
NO 2
C2 H5 COO
N N
Ph 8 67 12 60 3
H
H3C N S
H
OH O
85 65 6 27 3
N O Cl
Et
OH O
80 72 6 26 3
N O Cl
Me
OH O
N O
85 74 6 38 3
Me
OH O
90 75 6 36 3
N O Cl
Ph
OH O
85 65 6 28 3
N O OMe
Ph
O
N NH
OH
4.5 85 10 40 3
N O Cl
Et
O
N NH
OH
4.5 82 10 39 3
N O Cl
Me
O
N NH
OH
4.0 80 8 38 3
N O
Me
S
N NH
OH
4.0 82 8 38 3
N O Cl
Ph
S
N NH
OH
4.5 85 8 45 3
N O OMe
Ph
H 5 C6
H
Ph N N S
9 80 12 62 23
N
Ph C 6 H5
O
H3 CH4 C6
H
Ph N N S
8.5 87 11 65 23
N
Ph C6H4 CH3
O
H 3COH 4 C6
H
Ph N N S
8.0 91 11 68 23
N
Ph C 6H 4OCH 3
O
ClH4 C6
H
Ph N N S
8.0 90 11.5 65 23
N
Ph C6 H4 Cl
O


Structure Ref. No.
BrH 4C6
H
Ph N N S
8.5 85 12 67 23
N
Ph C 6H 4Br
O
HOH 4 C6
H
Ph N N S
9.0 82 12 60 23
N
Ph C 6H 4 OH
O
O 2NH 4C6
H
Ph N N S
8.0 87 12 70 23
N
Ph C6 H4NO 2
O
Furyl
H
Ph N N S
9 86 11 67 23
N
Ph Furyl
O
Thionyl
H
Ph N N S
8.5 92 11.5 72 23
N
Ph Thionyl
O
Pyridnyl
H
Ph N N S
9.0 80 12 60 23
N
Ph Pyridnyl
O
CN
Ph N
NH
5 75 7 53 24
Ph
C6H5 Ph
CN
Ph N
NH 4.5 78 6.5 54 24
Ph
Ph
CH3C6H4
CN
Ph N
NH 4 81 6.5 57 24
Ph
Ph
CH3OC 6H 4
CN
Ph N
NH 4 87 6 65 24
Ph
ClC 6H 4 Ph
CN
Ph N
NH 4.5 82 6.5 60 24
Ph
BrCH4 Ph
CN
Ph N
NH 5 73 7 52 24
Ph
Ph
OHC 6H 4
CN
Ph N
NH 4.5 85 6.5 63 24
Ph
Ph
No2 C6 H4
CN
Ph N
NH
4 79 6 56 24
Ph
Furyl Ph

Microwave Irradiation Conventional Heating Ref.

Structure
Time (min) Yield (%) Time (hr.) Yield (%) No.
CN
Ph N
NH 4 81 6 58 24
Ph
Ph
Thiodinyl
CN
Ph N
NH 4.5 76 7 56 24
Ph
Ph
Pyridinyl
20 82 5.5 65 24
HN NH
S
CH3
22 78 6 55 24
HN NH
S
CH3
22 80 6 54 24
HN NH
S
H3C
24 76 5.5 58 24
HN NH
S
OCH 3
26 78 6 60 24
HN NH
S
H3 CO
24 75 6 61 24
HN NH
S
H 3CO OCH 3
HN NH
25 73 6.5 65 24
S
(Me)2N
29 75 5.5 55 24
HN NH
R1
Benzil (2.5m mole; 5.25g), ethyl-1-formyl-1, 2, 3, 6-
R1
tetrahydro-4-methy-6-phenyl-2-thioxopyrimidine-5- R2
carboxylate and ammonium acetate were dissolved in C2H5COOH
N
R2
glacial acetic acid. The reaction mixture was subjected to C2H5COOH
Ammonium
acetate / acidic alumina
N
CHO N
microwave irradiation to procedure substituted ethyl 1, 2, N
+ O Microwave irradiation
H3C
N O H
8 - min H
3, 6-tetrahydro-4-methyl-2-oxo/thioxo-6-phenyl-1- (4, 5- H3C N O O
H
diphenyl-1-H-imidazol-2-yl) pyrimidine-5-carboxylate Scheme III
(scheme III)3.
Ph O O
The procedures for the Synthesis of 2-amino-3- C Basic alumina
+H5C6 NH2 C
ethylcarboxylate-4, 5-diphenylpyrroles were followed as: CH CH2
Ph OH Ph
2-amino-2-phenylacetophenones and cyano-ethyl acetate HN C 6H 5
were dissolved in 10 ml of EtOH and the resulting solution
Basic alumina NC CH2 COOEt
was adsorbed over 20g basic alumina or montmorillonite.
The beaker containing reaction mixture was then kept in C6 H 5 H H 5C 6 S
microwave oven in an alumina bath and irradiated for 6-7 N N NH C NH2 Ph COOEt
Ph S
minutes intermittently. Furthermore, synthesis of 2- Basic alumina Ph
thioxo-3, 7-disubstituted-5, 6-diphenyl-pyrrolo [2, 3-d] Ph
N N NH2
C 6H 5
pyrimidin-4(1H)-ones was carried out using conventional O H5 C 6
23
and microwave methods (Scheme IV) . Scheme IV
To produce 3, 4-dihydrobenzo 2, 3-d pyrimidines in dry 3. Ban M., Taquchi H., Katsushima T., Akoki S. and Wantanbe A.,
Synthesis of new calcineurin inhibitors via Pdcatalyzed cross-
media under microwave irradiations by the cyclization of
coupling reactions, Bioorg Med. Chem., 6, (1998) 1057-1067.
1, 3-cyclohexadiene derivatives with formamide under
24 4. Srivastva S.K., Agarwal A., Murthy P.K., Chauhan P. M. S., Agarwal
acidic conditions (Scheme V) .
S. K., Bhaduri A. P., Singh S. N., Fatima N. and Chatterjee R. K.,
Ph O Ph CN Synthesis of several new series of heterocyclo-thiazolidin-arylidine
CN
C Baisic Alumina and thiadiazolyl-azetidines Biological active molecule, J. Med.
+ H2C Chem. 42 (1999) 1667-1672.
CH CN Ph O NH2
Ph OH 5. Katritzky A. R., Regiospecific Synthesis of 4-(2-Oxoalkyl) pyridines,
In Comprehensive Hetrocyclic Chemistry Rees, 25 (1984)
Neutrarl Alumina
6. Dlugosz A. and Dus D., Synthesis and biological studies of some
novel schife and hydra zones darivatives from 8-hydroxy quinoline
moiety, Farmaco, 51 (1996) 367.
7. Afonso A. and Weinstein J., An efficient synthesis and DNA binding

O NH2 O NH2 interaction study of some novel heterocyclic
C CN fusedpyarzolequinolines: A potent antimicrobial agent, Gentles. M.
Ph O
CN J. U.S. US, 5 (1995) 382- 572.
C
H5 C6 Ph Ph 8. 8.Omar Abd El-Fattah, Eman Mostafa Hassan Abbas, Neama
Ph OH H3C Ph Ahmed Mohamed and Sherien I. Abd-Elmoez1, Synthesis and
Ph
Evaluation of Some Tetrahydropyrimidine Derivatives as
Antimicrobial, Australian Journal of Basic and Applied Sciences,
4(1), (2010) 27-36.
Acidic Alumina
9. Singh K., Arora D. and Balzarini J., Regioselective addition reactions
at C-2 of 3,4-dihydropyrimidinones, Tetrahedron, 66 (41), (2010)
8175-8180.
CN 10. Kappe C.O., Iologically active dihydropyrimidones of the Biginelli-

Ph N type – A literature survey, Eur. J. Med. Chem., 35, (2000) 1043-
1052.
NH 11. Saleh A. Bahashwan, Pharmacological Studies of Some Pyrimidino
Ph
C 6H 5 Ph Derivatives, African Journal of Pharmacy and Pharmacology, 5(4)
(2011) 527-531.
Scheme V
12. Ashok K. Rathod, Kulkarni G. B., Synthesis and Characterizations of
CONCLUSION Diphenyl Imidazolylpyrimidines -5-Carboxylates (DPIPC) Derivatives
and their Antifungal and Antibacterial Activity Under Conventional
Pyrimidine and pyrimidine derivatives have proved for and Microwave Irradiation Method, International Journal of
many years to have significant therapeutic potential. They PharmTech Research, 3 (2011) 435-441.
come from a wide variety of natural sources and new 13. Mohamed M.S., Awad S. M. and Ahmed N. M., Synthesis and
pyrimidine derivatives are being discovered or Antimicrobial Activities of New Indolyl-Pyrimidine Derivatives,
synthesized on a regular basis. It is evident from the Journal of Applied Pharmaceutical Science, 01, (2011) 76-80.
research described that pyrimidine and pyrimidine 14. Fathalla O.A., Zeid I.F, Haiba M.E., SolimanA.M., Sh. I. Abd-Elmoez
derivatives are a plentiful source of potential drugs and W.S. El-Serwy, Synthesis, Antibacterial and Anticancer
candidate in relation to its safety and efficacy. New Evaluation of Some Pyrimidine Derivatives, World Journal of
Chemistry, 4 (2009) 127-132.
pyrimidine derivatives have been synthesized using
conventional and microwave heating methodology and 15. Mazaahir Kidwai and Akkal Deo Mishra, An Expeditious Synthesis
of 3, 4-dihydrobenzo 2, 3-d Pyrimidines Using Inorganic Solid
characterized. The advantages in the use of microwave
Supports, J.Serb.Chem.Soc. 69, (2004) 247–254.
methodology are shorter reaction times, higher yields and
simplified work up procedures for the point of 16. Mohammed Abdalla Hussein, Synthesis and Biological Activity of
Some New Heterocyclic Systems Containing Pyrazolo [3,4-
purification of the prepared compound. The combination D]Pyrimidines, Imperial J. Medicinal and Organic Chemistry, 1
of solvent free reaction condition and microwave (2011).
irradiation leads to significantly reduced reaction times,
17. Raafat Soliman, Nargues S. Habib, Alaa A. EL-Tombary, Soad A. M.
enhanced conversions and sometime higher selectivity EL-Hawash, Omaima G. Shaaban, Synthesis of
with several advantages for the eco-friendly approach, Tetrahydrobenzothieno[2,3-d]pyrimidine and
termed as “Green Chemistry”. Tetrahydrobenzothieno[3,2-e]-[1,2,4]triazolo[4,3-c]pyrimidine
Derivatives as Potential Antimicrobial Agents, Sci Pharm., 77,
REFERENCES (2009) 755–773.
1. Javad Safaei Ghomi, Mohammad Ali, Ghasemzadeh, An Efficient 18. Said S.A. and Abdulla M.M., Synthesis and Antiflammatory
Route to The Synthesis of Pyrimidine-2-ones Under ultrasound Activities of Some New Pyridopyridine,Pyridipyrimidine and
Irradiation, Digest Journal of Nanomaterials and Biostructures, 5 Pyridopyrimidotriazine Derivatives, World applied sciencies
(2010) 303-306. journal, 9, (2010) 589-599.
2. Munawar Ali Munawar, Muhammad Azad, Hamid Latif Siddiquia 19. Mutlu Dilsiz Aytemir, Unsal Çalis and Meral Ozalp, Synthesis of
and Faiz-ul-Hassan Nasim, Synthesis and Antimicrobial Studies of Some New 3-Ethyl-6-phenylhexahydro Pyrimidine-2,4-dione
Some Quinolinylpyrimidine Derivatives, Journal of the Chinese Derivatives and Evaluation of Their In Vitro Antimicrobial
Chemical Society, 55 (2008) 394-400. Activities, Journal of Faculty of Pharmacy, 22, (2002) 9-18.

20. Prasenjit Mondal, Soma Jana and Lakshmi Kanta Kanthal, Synthsis 23. Mazaahir Kidwai and Akkal Deo Mishra, An expeditious Synthesis
of Novel Mercapto –Pyrimidine and Amino-Pyrimidine Derivatives of 3,4-dihydrobenzo 2,3-d_Pyrimidines Using Inorganic Solid
of Indoline -2-One as Potential Antioxident and Antibacterial Supports, J.Serb.Chem.Soc.,69, (2004) 247–254.
Agents, The Pharma Research, 3, (2010) 17-26.
24. Javad Safaei Ghomi and Mohammad Ali Ghasemzadeh,
21. Singh D. N., Verma N. and Pathak L.P., Synthesis and Ultrasound-assisted synthesis of dihydropyrimidine-2-thiones, J.
Antileishmanial Activity of Some New Substituted Imidazolo[3,2- Serb. Chem. Soc., 76, (2011) 679–684.
c]pyrimidines and Thieno[2,3-d]pyrimidines, J. Ind. Council Chem.,
27, (2010) 140-144. 25. Kamaljit Singh, Kawaljit Singh, Baojie Wan, Scott Franzblau, Kelly
Chibale and Jan Balzarini, Facile transformation of Biginelli
22. Mishra A. D., Dry Media Synthesis of Novel Pyrrolo-pyrimidines, J. Pyrimidin-2(1H)-ones to Pyrimidines In vitro Evaluation as
Nepal Chem. Soc., 25, (2010). Inhibitors of Mycobacterium Tuberculosis and Modulators of
Cytostatic Activity, European Journal of Medicinal Chemistry, 46,
(2011) 2290-2294.
********************


Comparitive Study of Microwave and Conventional Synthesis

Caricato da

Informazioni sul documento

Descrizione originale:

Titolo originale

Copyright

Formati disponibili

Condividi questo documento

Condividi o incorpora il documento

Opzioni di condivisione

Hai trovato utile questo documento?

Questo contenuto è inappropriato?

Copyright:

Formati disponibili

Comparitive Study of Microwave and Conventional Synthesis

Caricato da

Copyright:

Formati disponibili

Int. J. Pharm. Sci. Rev. Res.

, 15(1), 2012; nᵒ 04, 15-22 ISSN 0976 – 044X

COMPARATIVE STUDY OF MICROWAVE AND CONVENTIONAL SYNTHESIS

Accepted on: 02-03-2012; Finalized on: 30-06-2012.

INTRODUCTION hepatitis B virus replication inhibitors and depict a variety

Table 1: Pharmacological activities of Pyrimidines 17 N N Antimicrobial

11 CH3 Analgesic activity OCH 3

International Journal of Pharmaceutical Sciences Review and Research Page 16

International Journal of Pharmaceutical Sciences Review and Research Page 17

Microwave Irradiation Conventional Heating

International Journal of Pharmaceutical Sciences Review and Research Page 18

Microwave Irradiation Conventional Heating

International Journal of Pharmaceutical Sciences Review and Research Page 19

Microwave Irradiation Conventional Heating Ref.

7. Afonso A. and Weinstein J., An efficient synthesis and DNA binding

CN 10. Kappe C.O., Iologically active dihydropyrimidones of the Biginelli-

International Journal of Pharmaceutical Sciences Review and Research Page 21

International Journal of Pharmaceutical Sciences Review and Research Page 22

Potrebbero piacerti anche