Research Article Triphenylphosphine Mediated Synthesis of...
Transcript of Research Article Triphenylphosphine Mediated Synthesis of...
Hindawi Publishing CorporationJournal of ChemistryVolume 2013 Article ID 289636 5 pageshttpdxdoiorg1011552013289636
Research ArticleTriphenylphosphine Mediated Synthesis of FunctionalizedBenzo-Fused Coumarins from Some OH Acids and DialkylAcetylene Dicarboxylate
Bita Mohtat1 Semiramis Nahavandian1 Maryam Razaghi1
Saeedeh Farsijani1 and Hoorieh Djahaniani2
1 Chemistry Department Karaj Branch Islamic Azad University PO Box 31485-313 Karaj Iran2 Chemistry Department East Tehtan Branch Islamic Azad University PO Box 163-33955 Tehran Iran
Correspondence should be addressed to Bita Mohtat b mohtatyahoocom
Received 6 February 2013 Accepted 22 July 2013
Academic Editor Silvia Mari
Copyright copy 2013 Bita Mohtat et al This is an open access article distributed under the Creative Commons Attribution Licensewhich permits unrestricted use distribution and reproduction in any medium provided the original work is properly cited
Benzo-fused coumarins are prepared from 4-quinolinol by treatment with PPh3and dialkyl acetylenedicarboxylate Angular
coumarins are prepared from 3-isoquinolinol and 7-hydroxyl coumarine with PPh3and dialkyl acetylenedicarboxylate
1 Introduction
Coumarins comprise a very large class of compoundsfound throughout the plant kingdom [1] The bioactivity ofcoumarin andmore complex related derivatives appears to bebased on the coumarin nucleus [2 3] Coumarin compoundscan display anticancer anticoagulant antimicrobial anti-inflammatory and antioxidant activities [4ndash8]
In addition as an important class of organic heterocyclicdyes coumarin derivatives exhibit unique photochemical andphotophysical properties which render them useful in avariety of applications such as optical brighteners laser dyesnonlinear optical chromophores solar energy collectorsfluorescent labels and probes in biology and medicine andtwo-photon absorption (TPA) materials [9ndash12]
Coumarins have been synthesized by several methods[13ndash18] In the interest of synthesizing new coumarin ringsystems for possible evaluation as biologically active com-pounds we have described a synthesis of carboxymethylcoumarins from 3-hydroxyl pyridine [19] carboxylic systems[19ndash22] we wish to report here the synthesis of some benzo-fused coumarinsThe preparations of coumarins are depictedin Schemes 1 2 and 3
2 Experimental
21 General Compounds 1 2 and Ph3P were obtained from
Fluka and were used without further purification M pElectrothermal-9100 apparatus IR Spectra Shimadzu IR-460 spectrometer 1H- and 13CNMR spectra Bruker DRX-300 AVANCE instrument in CDCl
3at 300 and 75MHz
respectively 120575 in ppm EI-MS (70 eV) Finnigan-MAT-8430mass spectrometer inmz Elemental analyses (C H N) wereperformed with a Heraeus CHN-O-Rapid analyser
22 General Procedure for the Preparation of Compound 3To a stirred solution of 052 g of Ph
3P (2mmoL) and 028 g
1 (2mmoL) in toluene (10mL) was added dropwise a mixtureof 2 (2mmoL) in toluene (2mL) at room temperature over5min The reaction mixture was heated under reflux for24 h The solvent was removed under reduced pressure andthe viscous residue was purified by column chromatography(SiO2 hexaneAcOEt) to afford the pure adducts
Methyl 2-Oxo-2H-pyrano[32-c]quinoline-4-carboxylate (4a)Yellow powder 046 g (90) mp 119ndash121∘C IR (KBr)]maxcm
minus1 1744 (C=O) 1625 (C=N) 1HNMR (300MHzCDCl
3) 120575 408 (s 3H Me) 709 (s 1H CH) 770
2 Journal of Chemistry
N
OH OH
N
abc
2
1 2 3
H
N
O
O
abc
4
4
R R907772
CO2R
CO2RCO2R
CO2R
CO2R
+
Ph3P (15mol-)
Toluene reflux Toluene
MeEt
MeEt
Yield ()
t-Bu t-Bu
200∘C
Scheme 1 Typical procedure for compound 4
N
O
O
ab
MeEt
6 R
N
OH
2
Yield ()7671
5 6
+
RO2C
Ph3P (15mol-)
Toluene reflux
Scheme 2 Procedure for synthesis of compound 6
(t 1H 119869 = 65Hz CH) 788 (t 1H 119869 = 70 CH) 815 (d 1H119869 = 84Hz CH) 845 (d 1H 119869 = 79Hz CH) 971 (s 1HCH) 13CNMR (75MHz CDCl
3) 120575 536 (Me) 1079 (CH)
1177 (CH) 1196 (CH) 1276 (CH) 1293 (C) 1324 (CH) 1417(CH) 1477 (C) 1478 (C) 1489 (C) 1574 (C) 1586 (C=O)1635 (C=O) MS (EI)mz 255 (M+ 98) 227 (57) 196 (84)140 (43) Anal calcd for C
14H9NO4 C 6588 H 355 N 549
Found C 6587 H 357 N 547
Ethyl 2-Oxo-2H-pyrano[32-c]quinoline-4-carboxylate (4b)Yellow powder 041 g (77) mp 128ndash130∘C IR (KBr)]maxcm
minus1 1740 (C=O) 1634 (C=N) 1HNMR (300MHzCDCl
3) 120575 147 (t 3H 119869 = 71HzMe) 454 (q 2H 119869 = 71Hz
OCH2) 709 (s 1H CH) 781 (t 1H 119869 = 73Hz CH) 796
(t 1H 119869 = 69 CH) 814 (d 1H 119869 = 84Hz CH) 843 (d1H 119869 = 83Hz CH) 964 (s 1H CH) 13CNMR (75MHzCDCl
3) 120575 143 (Me) 635 (OCH
2) 1079 (CH) 1177 (CH)
1201 (CH) 1276 (CH) 1293 (C) 1324 (CH) 1417 (CH)1477 (C) 1478 (C) 1489 (C) 1574 (C) 1586 (C=O) 1635(C=O) MS (EI) mz 255 (M+ 98) 196 (72) 196 (69) 154(100) Anal calcd for C
15H11NO4 C 6691 H 412 N 520
Found C 6694 H 411 N 519
Tert-butyl 2-Oxo-2H-pyrano[32-c]quinoline-4-carboxylate(4c) Yellow powder 043 g (72) mp 130ndash132∘C IR (KBr)]maxcm
minus1 1723 (C=O) 1628 (C=N) 1HNMR (300MHzCDCl
3) 120575 170 (s 9H 3Me) 702 (s 1H CH) 780 (t 1H
119869 = 69Hz CH) 795 (t 1H 119869 = 69 CH) 813 (d 1H119869 = 84Hz CH) 842 (d 1H 119869 = 83Hz CH) 960 (s 1H
CH) 13CNMR (75MHz CDCl3) 120575 281 (3Me) 853 (C)
1079 (CH) 1185 (CH) 1195 (CH) 1286 (CH) 1303 (C)1328 (CH) 1417 (CH) 1477 (C) 1488 (C) 1498 (C) 1574(C) 1593 (C=O) 1634 (C=O) MS (EI) mz 255 (M+ 98)269 (86) 196 (48) 57 (100) Anal calcd for C
17H15NO4 C
6868 H 509 N 471 Found 6870 H 508 N 469
Methyl 3-Oxo-3H-pyrano[23-c]isoquinoline-1-carboxylate(6a) Yellow powder 069 g (76) mp 105ndash107∘C IR (KBr)]maxcm
minus1 1733 (C=O) 1651 (C=N) 1HNMR (300MHzCDCl
3) 120575 404 (s 3H Me) 688 (s 1H CH) 755 (t 1H
119869 = 77Hz CH) 767 (t 1H 119869 = 82Hz CH) 770 (d 1H119869 = 81Hz CH) 789 (d 1H 119869 = 81Hz CH) 924 (s 1HCH) 13CNMR (75MHz CDCl
3) 120575 538 (Me) 1103 (C)
1224 (CH) 1230 (CH) 1247 (CH) 1263 (CH) 1271 (CH)1285 (C) 1329 (C) 1402 (CH) 1436 (C) 1581 (C) 1640(C=O) 1664 (C=O) MS (EI)mz 255 (M+ 10) 288 (100)204 (43) 189 (72) 61 (100) Anal calcd for C
14H9NO4 C
6588 H 355 N 549 Found C 6584 H 356 N 547
Ethyl 3-Oxo-3H-pyrano[23-c]isoquinoline-1-carboxylate(6b) Yellow powder 038 g (71) mp 110ndash112∘C IR (KBr)]maxcm
minus1 1739 (C=O) 1636 (C=N) 1HNMR (300MHzCDCl
3) 120575 143 (t 3H 119869 = 71HzMe) 435 (q 2H 119869 = 71Hz
OCH2) 692 (s 1H CH) 747 (t 1H 119869 = 73Hz CH) 750
(t 1H 119869 = 80Hz CH) 766 (d 1H 119869 = 82Hz CH) 770(d 1H 119869 = 85Hz CH) 13CNMR (75MHz CDCl
3) 120575 140
(Me) 619 (OCH2) 1109 (C) 1226 (CH) 1235 (CH) 1251
(CH) 1261 (CH) 1277 (CH) 1287 (C) 1331 (C) 1401 (CH)
Journal of Chemistry 3
MeEt
Yield ()Yield ()
O O
O
ab
8 R
O OH
2
7 8
O O OO OO
a
9 R
9
9082
87
+ +
RO2C
Ph3P (15mol-)
Toluene reflux
CO2R
t-Bu
Scheme 3 Procedure for synthesis of compounds 8 9
1436 (C) 1579 (C) 1646 (C=O) 1660 (C=O) MS (EI) mz296 (M+ 10) 277 (100) 201 (43) 183 (52) 77 (68) Analcalcd for C
15H11NO4 C 6691 H 412 N 520 Found C
6694 H 410 N 521
Methyl 28-Dioxo-2H8H-pyrano[32-g]chromene-4-carboxy-late Yellow powder 050 g (90) mp 135ndash137∘C IR (KBr)]maxcm
minus1 1739 (C=O) 1HNMR (300MHz CDCl3) 120575 412
(s 3H Me) 643 (d 1H 119869 = 96Hz CH) 650 (s 1H CH)728 (d 1H 119869 = 87Hz CH) 766 (d 1H 119869 = 87Hz CH)772 (d 1H 119869 = 96Hz CH) 13CNMR (CDCl
3) 120575ppm 538
(OMe) 1054 (C) 1138 (CH) 1149 (C) 1152 (CH) 1158(CH) 1313 (CH) 1429 (CH) 1433 (C) 1561 (C) 1579 (C)1583 (C=O) 1654 (C=O) 1676 (C=O) MS (EI) mz 272(M+ 30) 258 (100) 231 (46) 146 (100) Anal calcd forC14H8O6 C 6177 H 296 Found C 5596 H 309 N 488
Ethyl 28-Dioxo-2H8H-pyrano[32-g]chromene-4-carboxy-late Yellow powder 038 g (67) mp 139ndash141∘C IR (KBr)]maxcm
minus1 1728 (C=O) 1HNMR (300MHz CDCl3) 120575 143
(t 3H 119869 = 71Hz Me) 435 (q 2H 119869 = 71Hz OCH2) 672
(d 1H 119869 = 96Hz CH) 695 (s 1H CH) 733 (s 1H CH)760 (d 1H 119869 = 96Hz CH) 855 (s 1H CH) 13CNMR(75MHz CDCl
3) 120575 140 (Me) 594 (OCH
2) 1050 (C) 1115
(CH) 1118 (C) 1134 (CH) 1150 (CH) 1317 (CH) 1422(CH) 1437 (C) 1558 (C) 1574 (C) 1613 (C=O) 1659(C=O) 1675 (C=O) MS (EI) mz 314 (M+ 41) 258 (53)231 (65) 170 (24) Anal calcd for C
15H10O6 C 6294 H
352 Found C 6297 H 348
Tert-butyl 28-Dioxo-2H8H-pyrano[32-f]chromene-10-car-boxylate Yellow powder 055 g (87) mp 150ndash152∘C IR(KBr) ]maxcm
minus1 1747 (C=O) 1HNMR (300MHz CDCl3)
120575 165 (s 9H 3Me) 647 (d 1H 119869 = 96Hz CH) 696 (s 1HCH) 730 (s 1H CH) 778 (d 1H 119869 = 96Hz CH) 862 (s1H CH) 13CNMR (75MHz CDCl
3) 120575 293 (3Me) 848 (C)
1052 (C) 1137 (CH) 1166 (C) 1191 (CH) 1273 (CH) 1323(CH) 1422 (CH) 1429 (C) 1559 (C) 1561 (C) 1594 (C=O)1625 (C=O) 1676 (C=O) MS (EI) mz 314 (M+ 41) 277(25) 258 (64) 231 (33) 57 (100) Anal calcd for C
17H14O6
C 6497 H 449 Found C 6495 H 448
3 Result and Discussion
Treatment of 4-hydroxyquinoline 1 with dialkyl acety-lene dicarboxylate 2 and PPh
3in toluene under reflux
afforded dimethyl 2-(4-hydroxy-2-methyl-3-quinolinyl)-2-butenedioate (3) [22] When compound 3 was heated at200ndash205∘C it transformed to methyl 2-oxo-2H-pyrano[32-c]quinoline-4-carboxylate 4 in good yield The analyticaland spectral data of the product agree with the structure 4suggested The products were separated by column chro-matography and identified as 4 based on their elementalanalyses and their IR 1H and 13CNMR spectral dataThe mass spectra of these compounds displayed molecularion peaks at appropriate mz values Its 1HNMR spectrumshowed 3H singlet at 120575 = 408 for only one methoxy groupand a singlet (1H) at 120575 = 709 for methine proton The13CNMR spectrum one carbon appeared for the coumarincarbonyl (120575 = 1586 ppm) and one carbon for the carbonylester moiety (120575 = 1635 ppm) The 1H and 13CNMR spectraof 4b and 4c are similar to those of 4a except for thealkoxy moieties which exhibited characteristic resonanceswith appropriate chemical shifts
Treatment of 3-isoquinolinol 5 with dialkyl acetylenedicarboxylate 2 and PPh
3in refluxing toluene for 24 h and
separation of the reaction mixture by column chromatog-raphy gave methyl 3-oxo-3H-pyrano[23-c]isoquinoline-1-carboxylate 6 in 76 yield (Scheme 3) obviously via areaction sequence similar to that depicted in Scheme 1 Thereaction with di-tert-butyl acetylene dicarboxylate was notdetected because of the bulky group (Scheme 2)
Next we studied the reaction of 7-hydroxy coumarine 7with dialkyl acetylene dicarboxylate and PPh
3in refluxing
toluene which resulted in the formation of the methyl28-dioxo-2H8H-pyrano[32-g]chromene-4-carboxylate 8(Scheme 3) The linear product 9 was detected and isolatedfrom the reaction with di-tert-butyl acetylene dicarboxylatebecause of the bulky group
Mechanistically [13 19] it is conceivable that the reactioninvolves the initial formation of a zwitterionic intermediatebetween Ph
3P and the acetylenic compound and subsequent
protonation of reactive 1 1 adduct followed by electrophilicattack of vinyltriphenylphosphonium cation on the aromatic
4 Journal of Chemistry
N
O
N
H
N
OHO
OMe
H10
4
CO2Me
CO2Me
PPh3+
+
minus
CHCO2MePh3P+
MeO2C
MeO2C
minusPPh3
O
Scheme 4
ring at the ortho position relative to the strong activationgroup The product is presumablyproduced by intramolecu-lar lactonization of the unsaturated diester 10 (Scheme 4)
4 Conclusion
From the above results we conclude that treatment of oxygenatom of the pyran ring belongs to the starting phenolwhile the periselectivity in the construction of this new ringdepends on the higher reactivity of the free o-positions ofthe phenol during the aromatic electrophilic substitutionsequenceThese functionalised coumarinsmay be consideredas potentially useful synthetic intermediates because theypossess atoms with different oxidation states The advantagesof presentmethod are the fact that it performed under neutralcondition and substances are utilized in their basic formwith-out anymodificationThe simplicity of the present proceduremakes it an interesting alternative to other approaches
Acknowledgment
The authors thank the Karaj Branch Islamic Azad Universityfor support of this work
References
[1] R D Murray J Mendez and S A Brown The NaturalCoumarins Occurrence Chemistry and Biochemistry JohnWiley amp Sons 1982
[2] F A Jimenez-Orozco J A Molina-Guarneros N Mendoza-Patino et al ldquoCytostatic activity of coumarin metabolitesand derivatives in the B16- F10 murine melanoma cell linerdquoMelanoma Research vol 9 no 3 pp 243ndash247 1999
[3] G J Finn B Creaven and D A Egan ldquoStudy of the invitro cytotoxic potential of natural and synthetic coumarinderivatives using human normal and neoplastic skin cell linesrdquoMelanoma Research vol 11 no 5 pp 461ndash467 2001
[4] D Yim R P Singh C Agarwal S Lee H Chi and R AgarwalldquoA novel anticancer agent decursin induces G1 arrest and
apoptosis in human prostate carcinoma cellsrdquo Cancer Researchvol 65 no 3 pp 1035ndash1044 2005
[5] M E Riveiro R Vazquez A Moglioni et al ldquoBiochemi-cal mechanisms underlying the pro-apoptotic activity of 78-dihydroxy-4-methylcoumarin in human leukemic cellsrdquo Bio-chemical Pharmacology vol 75 no 3 pp 725ndash736 2008
[6] I Kostova S Raleva P Genova and R Argirova ldquoStructure-activity relationships of synthetic coumarins as HIV-1inhibitorsrdquo Bioinorganic Chemistry and Applications vol2006 Article ID 68274 9 pages 2006
[7] B FGage ldquoPharmacogenetics-based coumarin therapyrdquoHema-tology vol 2006 no 1 pp 467ndash473 2006
[8] D A Ostrov J A Hernandez Prada P E Corsino K AFinton N Le and T C Rowe ldquoDiscovery of novel DNA gyraseinhibitors by high-throughput virtual screeningrdquo AntimicrobialAgents and Chemotherapy vol 51 no 10 pp 3688ndash3698 2007
[9] R M Melavanki R A Kusanur M V Kulakarni and J SKadadevarmath ldquoRole of solvent polarity on the fluorescencequenching of newly synthesized 78-benzo-4-azidomethylcoumarin by aniline in benzene-acetonitrile mixturesrdquo Journalof Luminescence vol 128 no 4 pp 573ndash577 2008
[10] T Z Yu P Zhang Y L Zhao H Zhang J Meng andD W Fan ldquoSynthesis and photoluminescent properties oftwo novel tripodal compounds containing coumarin moietiesrdquoSpectrochimica Acta A vol 73 no 1 pp 168ndash173 2009
[11] H Turki S Abid S Fery-Forgues and R El Gharbi ldquoOpticalproperties of newfluorescent iminocoumarins part 1rdquoDyes andPigments vol 73 no 3 pp 311ndash316 2007
[12] X Li Y X Zhao T Wang M Q Shi and F P WuldquoCoumarin derivatives with enhanced two-photon absorptioncross-sectionsrdquo Dyes and Pigments vol 74 no 1 pp 108ndash1122007
[13] I Yavari R Amiri and M Haghdadi ldquoTriphenyphosphine-mediated efficient synthesis of functionalized 2-OXO-2H-Chromenesrdquo Phosphorus Sulfur and Silicon and the RelatedElements vol 179 no 11 pp 2163ndash2168 2004
[14] E Galariniotou V Fragos A Makri K E Litinas and D NNicolaides ldquoSynthesis of novel pyridocoumarins and benzo-fused 6-azacoumarinsrdquo Tetrahedron vol 63 no 34 pp 8298ndash8304 2007
Journal of Chemistry 5
[15] S D Kudale and M N Deodhar ldquoSynthesis and evaluationof some coumarin containing potential antimicrobial agentsrdquoJournal of Chemistry vol 9 no 4 pp 2493ndash2500 2012
[16] M A Hosny M A Radwan and E A El-Sawy ldquoSynthesis andanticancer activity of some new derivatives of coumarin andquinolinyl mercaptotriazolesrdquo Journal of Chemistry vol 9 no4 pp 1737ndash1745 2012
[17] D Kini andMGhate ldquoSynthesis and oral hypoglycemic activityof 3-[51015840-Methyl-21015840- aryl-31015840-(thiazol-21015840-yl amino) thiazolidin-41015840-one]coumarin Derivativesrdquo Journal of Chemistry vol 8 no1 pp 386ndash390 2011
[18] J L Du L I Li and D H Zhang ldquoUltrasound promotedsynthesis of 3-carboxycoumarins in aqueous mediardquo Journal ofChemistry vol 3 p 1 2006
[19] B Mohtat I Yavari R E Ameri and E Salahia ldquoSynthesisof aza coumarines by nucleophilic addition of acetylenic esterscatalysed by Ph
3PrdquoCroaticaChemicaActa vol 84 no 1 pp 123ndash
126 2011[20] B Mohtat S Azimzadeh H Djahaniani and L Pirhadi ldquoPh
3P
catalyzed synthesis of alkyl 2-(4-oxopyridin-1(4H)-Yl) acrylatesby nucleophilic addition to alkyl propiolatesrdquo South AfricanJournal of Chemistry vol 63 pp 204ndash206 2010
[21] B Mohtat Z N Azar S Nahavandian H Djahanianiand A Ahmadi ldquoSynthesis of dialkyl 2-(4-oxopyridin-1(4H)-yl)dicarboxylates through the reaction of 4-hydroxypyridineand dialkyl acetylenedicarboxylate in the presence of triph-enylphosphinerdquo Journal of the Mexican Chemical Society vol55 no 3 pp 194ndash196 2011
[22] B Mohtat S Nahavandian N Z Azar H Djahaniani andZ Hossaini ldquoTriphenylphosphine-promoted c-vinylation of 4-hydroxyquinolinesrdquo Zeitschrift fur Naturforschung vol 66 no7 pp 700ndash704 2011
Submit your manuscripts athttpwwwhindawicom
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Inorganic ChemistryInternational Journal of
Hindawi Publishing Corporation httpwwwhindawicom Volume 2014
International Journal ofPhotoenergy
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Carbohydrate Chemistry
International Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Chemistry
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Advances in
Physical Chemistry
Hindawi Publishing Corporationhttpwwwhindawicom
Analytical Methods in Chemistry
Journal of
Volume 2014
Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
SpectroscopyInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014
Medicinal ChemistryInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Chromatography Research International
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Applied ChemistryJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Theoretical ChemistryJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Spectroscopy
Analytical ChemistryInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Quantum Chemistry
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Organic Chemistry International
ElectrochemistryInternational Journal of
Hindawi Publishing Corporation httpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
CatalystsJournal of
2 Journal of Chemistry
N
OH OH
N
abc
2
1 2 3
H
N
O
O
abc
4
4
R R907772
CO2R
CO2RCO2R
CO2R
CO2R
+
Ph3P (15mol-)
Toluene reflux Toluene
MeEt
MeEt
Yield ()
t-Bu t-Bu
200∘C
Scheme 1 Typical procedure for compound 4
N
O
O
ab
MeEt
6 R
N
OH
2
Yield ()7671
5 6
+
RO2C
Ph3P (15mol-)
Toluene reflux
Scheme 2 Procedure for synthesis of compound 6
(t 1H 119869 = 65Hz CH) 788 (t 1H 119869 = 70 CH) 815 (d 1H119869 = 84Hz CH) 845 (d 1H 119869 = 79Hz CH) 971 (s 1HCH) 13CNMR (75MHz CDCl
3) 120575 536 (Me) 1079 (CH)
1177 (CH) 1196 (CH) 1276 (CH) 1293 (C) 1324 (CH) 1417(CH) 1477 (C) 1478 (C) 1489 (C) 1574 (C) 1586 (C=O)1635 (C=O) MS (EI)mz 255 (M+ 98) 227 (57) 196 (84)140 (43) Anal calcd for C
14H9NO4 C 6588 H 355 N 549
Found C 6587 H 357 N 547
Ethyl 2-Oxo-2H-pyrano[32-c]quinoline-4-carboxylate (4b)Yellow powder 041 g (77) mp 128ndash130∘C IR (KBr)]maxcm
minus1 1740 (C=O) 1634 (C=N) 1HNMR (300MHzCDCl
3) 120575 147 (t 3H 119869 = 71HzMe) 454 (q 2H 119869 = 71Hz
OCH2) 709 (s 1H CH) 781 (t 1H 119869 = 73Hz CH) 796
(t 1H 119869 = 69 CH) 814 (d 1H 119869 = 84Hz CH) 843 (d1H 119869 = 83Hz CH) 964 (s 1H CH) 13CNMR (75MHzCDCl
3) 120575 143 (Me) 635 (OCH
2) 1079 (CH) 1177 (CH)
1201 (CH) 1276 (CH) 1293 (C) 1324 (CH) 1417 (CH)1477 (C) 1478 (C) 1489 (C) 1574 (C) 1586 (C=O) 1635(C=O) MS (EI) mz 255 (M+ 98) 196 (72) 196 (69) 154(100) Anal calcd for C
15H11NO4 C 6691 H 412 N 520
Found C 6694 H 411 N 519
Tert-butyl 2-Oxo-2H-pyrano[32-c]quinoline-4-carboxylate(4c) Yellow powder 043 g (72) mp 130ndash132∘C IR (KBr)]maxcm
minus1 1723 (C=O) 1628 (C=N) 1HNMR (300MHzCDCl
3) 120575 170 (s 9H 3Me) 702 (s 1H CH) 780 (t 1H
119869 = 69Hz CH) 795 (t 1H 119869 = 69 CH) 813 (d 1H119869 = 84Hz CH) 842 (d 1H 119869 = 83Hz CH) 960 (s 1H
CH) 13CNMR (75MHz CDCl3) 120575 281 (3Me) 853 (C)
1079 (CH) 1185 (CH) 1195 (CH) 1286 (CH) 1303 (C)1328 (CH) 1417 (CH) 1477 (C) 1488 (C) 1498 (C) 1574(C) 1593 (C=O) 1634 (C=O) MS (EI) mz 255 (M+ 98)269 (86) 196 (48) 57 (100) Anal calcd for C
17H15NO4 C
6868 H 509 N 471 Found 6870 H 508 N 469
Methyl 3-Oxo-3H-pyrano[23-c]isoquinoline-1-carboxylate(6a) Yellow powder 069 g (76) mp 105ndash107∘C IR (KBr)]maxcm
minus1 1733 (C=O) 1651 (C=N) 1HNMR (300MHzCDCl
3) 120575 404 (s 3H Me) 688 (s 1H CH) 755 (t 1H
119869 = 77Hz CH) 767 (t 1H 119869 = 82Hz CH) 770 (d 1H119869 = 81Hz CH) 789 (d 1H 119869 = 81Hz CH) 924 (s 1HCH) 13CNMR (75MHz CDCl
3) 120575 538 (Me) 1103 (C)
1224 (CH) 1230 (CH) 1247 (CH) 1263 (CH) 1271 (CH)1285 (C) 1329 (C) 1402 (CH) 1436 (C) 1581 (C) 1640(C=O) 1664 (C=O) MS (EI)mz 255 (M+ 10) 288 (100)204 (43) 189 (72) 61 (100) Anal calcd for C
14H9NO4 C
6588 H 355 N 549 Found C 6584 H 356 N 547
Ethyl 3-Oxo-3H-pyrano[23-c]isoquinoline-1-carboxylate(6b) Yellow powder 038 g (71) mp 110ndash112∘C IR (KBr)]maxcm
minus1 1739 (C=O) 1636 (C=N) 1HNMR (300MHzCDCl
3) 120575 143 (t 3H 119869 = 71HzMe) 435 (q 2H 119869 = 71Hz
OCH2) 692 (s 1H CH) 747 (t 1H 119869 = 73Hz CH) 750
(t 1H 119869 = 80Hz CH) 766 (d 1H 119869 = 82Hz CH) 770(d 1H 119869 = 85Hz CH) 13CNMR (75MHz CDCl
3) 120575 140
(Me) 619 (OCH2) 1109 (C) 1226 (CH) 1235 (CH) 1251
(CH) 1261 (CH) 1277 (CH) 1287 (C) 1331 (C) 1401 (CH)
Journal of Chemistry 3
MeEt
Yield ()Yield ()
O O
O
ab
8 R
O OH
2
7 8
O O OO OO
a
9 R
9
9082
87
+ +
RO2C
Ph3P (15mol-)
Toluene reflux
CO2R
t-Bu
Scheme 3 Procedure for synthesis of compounds 8 9
1436 (C) 1579 (C) 1646 (C=O) 1660 (C=O) MS (EI) mz296 (M+ 10) 277 (100) 201 (43) 183 (52) 77 (68) Analcalcd for C
15H11NO4 C 6691 H 412 N 520 Found C
6694 H 410 N 521
Methyl 28-Dioxo-2H8H-pyrano[32-g]chromene-4-carboxy-late Yellow powder 050 g (90) mp 135ndash137∘C IR (KBr)]maxcm
minus1 1739 (C=O) 1HNMR (300MHz CDCl3) 120575 412
(s 3H Me) 643 (d 1H 119869 = 96Hz CH) 650 (s 1H CH)728 (d 1H 119869 = 87Hz CH) 766 (d 1H 119869 = 87Hz CH)772 (d 1H 119869 = 96Hz CH) 13CNMR (CDCl
3) 120575ppm 538
(OMe) 1054 (C) 1138 (CH) 1149 (C) 1152 (CH) 1158(CH) 1313 (CH) 1429 (CH) 1433 (C) 1561 (C) 1579 (C)1583 (C=O) 1654 (C=O) 1676 (C=O) MS (EI) mz 272(M+ 30) 258 (100) 231 (46) 146 (100) Anal calcd forC14H8O6 C 6177 H 296 Found C 5596 H 309 N 488
Ethyl 28-Dioxo-2H8H-pyrano[32-g]chromene-4-carboxy-late Yellow powder 038 g (67) mp 139ndash141∘C IR (KBr)]maxcm
minus1 1728 (C=O) 1HNMR (300MHz CDCl3) 120575 143
(t 3H 119869 = 71Hz Me) 435 (q 2H 119869 = 71Hz OCH2) 672
(d 1H 119869 = 96Hz CH) 695 (s 1H CH) 733 (s 1H CH)760 (d 1H 119869 = 96Hz CH) 855 (s 1H CH) 13CNMR(75MHz CDCl
3) 120575 140 (Me) 594 (OCH
2) 1050 (C) 1115
(CH) 1118 (C) 1134 (CH) 1150 (CH) 1317 (CH) 1422(CH) 1437 (C) 1558 (C) 1574 (C) 1613 (C=O) 1659(C=O) 1675 (C=O) MS (EI) mz 314 (M+ 41) 258 (53)231 (65) 170 (24) Anal calcd for C
15H10O6 C 6294 H
352 Found C 6297 H 348
Tert-butyl 28-Dioxo-2H8H-pyrano[32-f]chromene-10-car-boxylate Yellow powder 055 g (87) mp 150ndash152∘C IR(KBr) ]maxcm
minus1 1747 (C=O) 1HNMR (300MHz CDCl3)
120575 165 (s 9H 3Me) 647 (d 1H 119869 = 96Hz CH) 696 (s 1HCH) 730 (s 1H CH) 778 (d 1H 119869 = 96Hz CH) 862 (s1H CH) 13CNMR (75MHz CDCl
3) 120575 293 (3Me) 848 (C)
1052 (C) 1137 (CH) 1166 (C) 1191 (CH) 1273 (CH) 1323(CH) 1422 (CH) 1429 (C) 1559 (C) 1561 (C) 1594 (C=O)1625 (C=O) 1676 (C=O) MS (EI) mz 314 (M+ 41) 277(25) 258 (64) 231 (33) 57 (100) Anal calcd for C
17H14O6
C 6497 H 449 Found C 6495 H 448
3 Result and Discussion
Treatment of 4-hydroxyquinoline 1 with dialkyl acety-lene dicarboxylate 2 and PPh
3in toluene under reflux
afforded dimethyl 2-(4-hydroxy-2-methyl-3-quinolinyl)-2-butenedioate (3) [22] When compound 3 was heated at200ndash205∘C it transformed to methyl 2-oxo-2H-pyrano[32-c]quinoline-4-carboxylate 4 in good yield The analyticaland spectral data of the product agree with the structure 4suggested The products were separated by column chro-matography and identified as 4 based on their elementalanalyses and their IR 1H and 13CNMR spectral dataThe mass spectra of these compounds displayed molecularion peaks at appropriate mz values Its 1HNMR spectrumshowed 3H singlet at 120575 = 408 for only one methoxy groupand a singlet (1H) at 120575 = 709 for methine proton The13CNMR spectrum one carbon appeared for the coumarincarbonyl (120575 = 1586 ppm) and one carbon for the carbonylester moiety (120575 = 1635 ppm) The 1H and 13CNMR spectraof 4b and 4c are similar to those of 4a except for thealkoxy moieties which exhibited characteristic resonanceswith appropriate chemical shifts
Treatment of 3-isoquinolinol 5 with dialkyl acetylenedicarboxylate 2 and PPh
3in refluxing toluene for 24 h and
separation of the reaction mixture by column chromatog-raphy gave methyl 3-oxo-3H-pyrano[23-c]isoquinoline-1-carboxylate 6 in 76 yield (Scheme 3) obviously via areaction sequence similar to that depicted in Scheme 1 Thereaction with di-tert-butyl acetylene dicarboxylate was notdetected because of the bulky group (Scheme 2)
Next we studied the reaction of 7-hydroxy coumarine 7with dialkyl acetylene dicarboxylate and PPh
3in refluxing
toluene which resulted in the formation of the methyl28-dioxo-2H8H-pyrano[32-g]chromene-4-carboxylate 8(Scheme 3) The linear product 9 was detected and isolatedfrom the reaction with di-tert-butyl acetylene dicarboxylatebecause of the bulky group
Mechanistically [13 19] it is conceivable that the reactioninvolves the initial formation of a zwitterionic intermediatebetween Ph
3P and the acetylenic compound and subsequent
protonation of reactive 1 1 adduct followed by electrophilicattack of vinyltriphenylphosphonium cation on the aromatic
4 Journal of Chemistry
N
O
N
H
N
OHO
OMe
H10
4
CO2Me
CO2Me
PPh3+
+
minus
CHCO2MePh3P+
MeO2C
MeO2C
minusPPh3
O
Scheme 4
ring at the ortho position relative to the strong activationgroup The product is presumablyproduced by intramolecu-lar lactonization of the unsaturated diester 10 (Scheme 4)
4 Conclusion
From the above results we conclude that treatment of oxygenatom of the pyran ring belongs to the starting phenolwhile the periselectivity in the construction of this new ringdepends on the higher reactivity of the free o-positions ofthe phenol during the aromatic electrophilic substitutionsequenceThese functionalised coumarinsmay be consideredas potentially useful synthetic intermediates because theypossess atoms with different oxidation states The advantagesof presentmethod are the fact that it performed under neutralcondition and substances are utilized in their basic formwith-out anymodificationThe simplicity of the present proceduremakes it an interesting alternative to other approaches
Acknowledgment
The authors thank the Karaj Branch Islamic Azad Universityfor support of this work
References
[1] R D Murray J Mendez and S A Brown The NaturalCoumarins Occurrence Chemistry and Biochemistry JohnWiley amp Sons 1982
[2] F A Jimenez-Orozco J A Molina-Guarneros N Mendoza-Patino et al ldquoCytostatic activity of coumarin metabolitesand derivatives in the B16- F10 murine melanoma cell linerdquoMelanoma Research vol 9 no 3 pp 243ndash247 1999
[3] G J Finn B Creaven and D A Egan ldquoStudy of the invitro cytotoxic potential of natural and synthetic coumarinderivatives using human normal and neoplastic skin cell linesrdquoMelanoma Research vol 11 no 5 pp 461ndash467 2001
[4] D Yim R P Singh C Agarwal S Lee H Chi and R AgarwalldquoA novel anticancer agent decursin induces G1 arrest and
apoptosis in human prostate carcinoma cellsrdquo Cancer Researchvol 65 no 3 pp 1035ndash1044 2005
[5] M E Riveiro R Vazquez A Moglioni et al ldquoBiochemi-cal mechanisms underlying the pro-apoptotic activity of 78-dihydroxy-4-methylcoumarin in human leukemic cellsrdquo Bio-chemical Pharmacology vol 75 no 3 pp 725ndash736 2008
[6] I Kostova S Raleva P Genova and R Argirova ldquoStructure-activity relationships of synthetic coumarins as HIV-1inhibitorsrdquo Bioinorganic Chemistry and Applications vol2006 Article ID 68274 9 pages 2006
[7] B FGage ldquoPharmacogenetics-based coumarin therapyrdquoHema-tology vol 2006 no 1 pp 467ndash473 2006
[8] D A Ostrov J A Hernandez Prada P E Corsino K AFinton N Le and T C Rowe ldquoDiscovery of novel DNA gyraseinhibitors by high-throughput virtual screeningrdquo AntimicrobialAgents and Chemotherapy vol 51 no 10 pp 3688ndash3698 2007
[9] R M Melavanki R A Kusanur M V Kulakarni and J SKadadevarmath ldquoRole of solvent polarity on the fluorescencequenching of newly synthesized 78-benzo-4-azidomethylcoumarin by aniline in benzene-acetonitrile mixturesrdquo Journalof Luminescence vol 128 no 4 pp 573ndash577 2008
[10] T Z Yu P Zhang Y L Zhao H Zhang J Meng andD W Fan ldquoSynthesis and photoluminescent properties oftwo novel tripodal compounds containing coumarin moietiesrdquoSpectrochimica Acta A vol 73 no 1 pp 168ndash173 2009
[11] H Turki S Abid S Fery-Forgues and R El Gharbi ldquoOpticalproperties of newfluorescent iminocoumarins part 1rdquoDyes andPigments vol 73 no 3 pp 311ndash316 2007
[12] X Li Y X Zhao T Wang M Q Shi and F P WuldquoCoumarin derivatives with enhanced two-photon absorptioncross-sectionsrdquo Dyes and Pigments vol 74 no 1 pp 108ndash1122007
[13] I Yavari R Amiri and M Haghdadi ldquoTriphenyphosphine-mediated efficient synthesis of functionalized 2-OXO-2H-Chromenesrdquo Phosphorus Sulfur and Silicon and the RelatedElements vol 179 no 11 pp 2163ndash2168 2004
[14] E Galariniotou V Fragos A Makri K E Litinas and D NNicolaides ldquoSynthesis of novel pyridocoumarins and benzo-fused 6-azacoumarinsrdquo Tetrahedron vol 63 no 34 pp 8298ndash8304 2007
Journal of Chemistry 5
[15] S D Kudale and M N Deodhar ldquoSynthesis and evaluationof some coumarin containing potential antimicrobial agentsrdquoJournal of Chemistry vol 9 no 4 pp 2493ndash2500 2012
[16] M A Hosny M A Radwan and E A El-Sawy ldquoSynthesis andanticancer activity of some new derivatives of coumarin andquinolinyl mercaptotriazolesrdquo Journal of Chemistry vol 9 no4 pp 1737ndash1745 2012
[17] D Kini andMGhate ldquoSynthesis and oral hypoglycemic activityof 3-[51015840-Methyl-21015840- aryl-31015840-(thiazol-21015840-yl amino) thiazolidin-41015840-one]coumarin Derivativesrdquo Journal of Chemistry vol 8 no1 pp 386ndash390 2011
[18] J L Du L I Li and D H Zhang ldquoUltrasound promotedsynthesis of 3-carboxycoumarins in aqueous mediardquo Journal ofChemistry vol 3 p 1 2006
[19] B Mohtat I Yavari R E Ameri and E Salahia ldquoSynthesisof aza coumarines by nucleophilic addition of acetylenic esterscatalysed by Ph
3PrdquoCroaticaChemicaActa vol 84 no 1 pp 123ndash
126 2011[20] B Mohtat S Azimzadeh H Djahaniani and L Pirhadi ldquoPh
3P
catalyzed synthesis of alkyl 2-(4-oxopyridin-1(4H)-Yl) acrylatesby nucleophilic addition to alkyl propiolatesrdquo South AfricanJournal of Chemistry vol 63 pp 204ndash206 2010
[21] B Mohtat Z N Azar S Nahavandian H Djahanianiand A Ahmadi ldquoSynthesis of dialkyl 2-(4-oxopyridin-1(4H)-yl)dicarboxylates through the reaction of 4-hydroxypyridineand dialkyl acetylenedicarboxylate in the presence of triph-enylphosphinerdquo Journal of the Mexican Chemical Society vol55 no 3 pp 194ndash196 2011
[22] B Mohtat S Nahavandian N Z Azar H Djahaniani andZ Hossaini ldquoTriphenylphosphine-promoted c-vinylation of 4-hydroxyquinolinesrdquo Zeitschrift fur Naturforschung vol 66 no7 pp 700ndash704 2011
Submit your manuscripts athttpwwwhindawicom
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Inorganic ChemistryInternational Journal of
Hindawi Publishing Corporation httpwwwhindawicom Volume 2014
International Journal ofPhotoenergy
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Carbohydrate Chemistry
International Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Chemistry
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Advances in
Physical Chemistry
Hindawi Publishing Corporationhttpwwwhindawicom
Analytical Methods in Chemistry
Journal of
Volume 2014
Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
SpectroscopyInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014
Medicinal ChemistryInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Chromatography Research International
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Applied ChemistryJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Theoretical ChemistryJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Spectroscopy
Analytical ChemistryInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Quantum Chemistry
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Organic Chemistry International
ElectrochemistryInternational Journal of
Hindawi Publishing Corporation httpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
CatalystsJournal of
Journal of Chemistry 3
MeEt
Yield ()Yield ()
O O
O
ab
8 R
O OH
2
7 8
O O OO OO
a
9 R
9
9082
87
+ +
RO2C
Ph3P (15mol-)
Toluene reflux
CO2R
t-Bu
Scheme 3 Procedure for synthesis of compounds 8 9
1436 (C) 1579 (C) 1646 (C=O) 1660 (C=O) MS (EI) mz296 (M+ 10) 277 (100) 201 (43) 183 (52) 77 (68) Analcalcd for C
15H11NO4 C 6691 H 412 N 520 Found C
6694 H 410 N 521
Methyl 28-Dioxo-2H8H-pyrano[32-g]chromene-4-carboxy-late Yellow powder 050 g (90) mp 135ndash137∘C IR (KBr)]maxcm
minus1 1739 (C=O) 1HNMR (300MHz CDCl3) 120575 412
(s 3H Me) 643 (d 1H 119869 = 96Hz CH) 650 (s 1H CH)728 (d 1H 119869 = 87Hz CH) 766 (d 1H 119869 = 87Hz CH)772 (d 1H 119869 = 96Hz CH) 13CNMR (CDCl
3) 120575ppm 538
(OMe) 1054 (C) 1138 (CH) 1149 (C) 1152 (CH) 1158(CH) 1313 (CH) 1429 (CH) 1433 (C) 1561 (C) 1579 (C)1583 (C=O) 1654 (C=O) 1676 (C=O) MS (EI) mz 272(M+ 30) 258 (100) 231 (46) 146 (100) Anal calcd forC14H8O6 C 6177 H 296 Found C 5596 H 309 N 488
Ethyl 28-Dioxo-2H8H-pyrano[32-g]chromene-4-carboxy-late Yellow powder 038 g (67) mp 139ndash141∘C IR (KBr)]maxcm
minus1 1728 (C=O) 1HNMR (300MHz CDCl3) 120575 143
(t 3H 119869 = 71Hz Me) 435 (q 2H 119869 = 71Hz OCH2) 672
(d 1H 119869 = 96Hz CH) 695 (s 1H CH) 733 (s 1H CH)760 (d 1H 119869 = 96Hz CH) 855 (s 1H CH) 13CNMR(75MHz CDCl
3) 120575 140 (Me) 594 (OCH
2) 1050 (C) 1115
(CH) 1118 (C) 1134 (CH) 1150 (CH) 1317 (CH) 1422(CH) 1437 (C) 1558 (C) 1574 (C) 1613 (C=O) 1659(C=O) 1675 (C=O) MS (EI) mz 314 (M+ 41) 258 (53)231 (65) 170 (24) Anal calcd for C
15H10O6 C 6294 H
352 Found C 6297 H 348
Tert-butyl 28-Dioxo-2H8H-pyrano[32-f]chromene-10-car-boxylate Yellow powder 055 g (87) mp 150ndash152∘C IR(KBr) ]maxcm
minus1 1747 (C=O) 1HNMR (300MHz CDCl3)
120575 165 (s 9H 3Me) 647 (d 1H 119869 = 96Hz CH) 696 (s 1HCH) 730 (s 1H CH) 778 (d 1H 119869 = 96Hz CH) 862 (s1H CH) 13CNMR (75MHz CDCl
3) 120575 293 (3Me) 848 (C)
1052 (C) 1137 (CH) 1166 (C) 1191 (CH) 1273 (CH) 1323(CH) 1422 (CH) 1429 (C) 1559 (C) 1561 (C) 1594 (C=O)1625 (C=O) 1676 (C=O) MS (EI) mz 314 (M+ 41) 277(25) 258 (64) 231 (33) 57 (100) Anal calcd for C
17H14O6
C 6497 H 449 Found C 6495 H 448
3 Result and Discussion
Treatment of 4-hydroxyquinoline 1 with dialkyl acety-lene dicarboxylate 2 and PPh
3in toluene under reflux
afforded dimethyl 2-(4-hydroxy-2-methyl-3-quinolinyl)-2-butenedioate (3) [22] When compound 3 was heated at200ndash205∘C it transformed to methyl 2-oxo-2H-pyrano[32-c]quinoline-4-carboxylate 4 in good yield The analyticaland spectral data of the product agree with the structure 4suggested The products were separated by column chro-matography and identified as 4 based on their elementalanalyses and their IR 1H and 13CNMR spectral dataThe mass spectra of these compounds displayed molecularion peaks at appropriate mz values Its 1HNMR spectrumshowed 3H singlet at 120575 = 408 for only one methoxy groupand a singlet (1H) at 120575 = 709 for methine proton The13CNMR spectrum one carbon appeared for the coumarincarbonyl (120575 = 1586 ppm) and one carbon for the carbonylester moiety (120575 = 1635 ppm) The 1H and 13CNMR spectraof 4b and 4c are similar to those of 4a except for thealkoxy moieties which exhibited characteristic resonanceswith appropriate chemical shifts
Treatment of 3-isoquinolinol 5 with dialkyl acetylenedicarboxylate 2 and PPh
3in refluxing toluene for 24 h and
separation of the reaction mixture by column chromatog-raphy gave methyl 3-oxo-3H-pyrano[23-c]isoquinoline-1-carboxylate 6 in 76 yield (Scheme 3) obviously via areaction sequence similar to that depicted in Scheme 1 Thereaction with di-tert-butyl acetylene dicarboxylate was notdetected because of the bulky group (Scheme 2)
Next we studied the reaction of 7-hydroxy coumarine 7with dialkyl acetylene dicarboxylate and PPh
3in refluxing
toluene which resulted in the formation of the methyl28-dioxo-2H8H-pyrano[32-g]chromene-4-carboxylate 8(Scheme 3) The linear product 9 was detected and isolatedfrom the reaction with di-tert-butyl acetylene dicarboxylatebecause of the bulky group
Mechanistically [13 19] it is conceivable that the reactioninvolves the initial formation of a zwitterionic intermediatebetween Ph
3P and the acetylenic compound and subsequent
protonation of reactive 1 1 adduct followed by electrophilicattack of vinyltriphenylphosphonium cation on the aromatic
4 Journal of Chemistry
N
O
N
H
N
OHO
OMe
H10
4
CO2Me
CO2Me
PPh3+
+
minus
CHCO2MePh3P+
MeO2C
MeO2C
minusPPh3
O
Scheme 4
ring at the ortho position relative to the strong activationgroup The product is presumablyproduced by intramolecu-lar lactonization of the unsaturated diester 10 (Scheme 4)
4 Conclusion
From the above results we conclude that treatment of oxygenatom of the pyran ring belongs to the starting phenolwhile the periselectivity in the construction of this new ringdepends on the higher reactivity of the free o-positions ofthe phenol during the aromatic electrophilic substitutionsequenceThese functionalised coumarinsmay be consideredas potentially useful synthetic intermediates because theypossess atoms with different oxidation states The advantagesof presentmethod are the fact that it performed under neutralcondition and substances are utilized in their basic formwith-out anymodificationThe simplicity of the present proceduremakes it an interesting alternative to other approaches
Acknowledgment
The authors thank the Karaj Branch Islamic Azad Universityfor support of this work
References
[1] R D Murray J Mendez and S A Brown The NaturalCoumarins Occurrence Chemistry and Biochemistry JohnWiley amp Sons 1982
[2] F A Jimenez-Orozco J A Molina-Guarneros N Mendoza-Patino et al ldquoCytostatic activity of coumarin metabolitesand derivatives in the B16- F10 murine melanoma cell linerdquoMelanoma Research vol 9 no 3 pp 243ndash247 1999
[3] G J Finn B Creaven and D A Egan ldquoStudy of the invitro cytotoxic potential of natural and synthetic coumarinderivatives using human normal and neoplastic skin cell linesrdquoMelanoma Research vol 11 no 5 pp 461ndash467 2001
[4] D Yim R P Singh C Agarwal S Lee H Chi and R AgarwalldquoA novel anticancer agent decursin induces G1 arrest and
apoptosis in human prostate carcinoma cellsrdquo Cancer Researchvol 65 no 3 pp 1035ndash1044 2005
[5] M E Riveiro R Vazquez A Moglioni et al ldquoBiochemi-cal mechanisms underlying the pro-apoptotic activity of 78-dihydroxy-4-methylcoumarin in human leukemic cellsrdquo Bio-chemical Pharmacology vol 75 no 3 pp 725ndash736 2008
[6] I Kostova S Raleva P Genova and R Argirova ldquoStructure-activity relationships of synthetic coumarins as HIV-1inhibitorsrdquo Bioinorganic Chemistry and Applications vol2006 Article ID 68274 9 pages 2006
[7] B FGage ldquoPharmacogenetics-based coumarin therapyrdquoHema-tology vol 2006 no 1 pp 467ndash473 2006
[8] D A Ostrov J A Hernandez Prada P E Corsino K AFinton N Le and T C Rowe ldquoDiscovery of novel DNA gyraseinhibitors by high-throughput virtual screeningrdquo AntimicrobialAgents and Chemotherapy vol 51 no 10 pp 3688ndash3698 2007
[9] R M Melavanki R A Kusanur M V Kulakarni and J SKadadevarmath ldquoRole of solvent polarity on the fluorescencequenching of newly synthesized 78-benzo-4-azidomethylcoumarin by aniline in benzene-acetonitrile mixturesrdquo Journalof Luminescence vol 128 no 4 pp 573ndash577 2008
[10] T Z Yu P Zhang Y L Zhao H Zhang J Meng andD W Fan ldquoSynthesis and photoluminescent properties oftwo novel tripodal compounds containing coumarin moietiesrdquoSpectrochimica Acta A vol 73 no 1 pp 168ndash173 2009
[11] H Turki S Abid S Fery-Forgues and R El Gharbi ldquoOpticalproperties of newfluorescent iminocoumarins part 1rdquoDyes andPigments vol 73 no 3 pp 311ndash316 2007
[12] X Li Y X Zhao T Wang M Q Shi and F P WuldquoCoumarin derivatives with enhanced two-photon absorptioncross-sectionsrdquo Dyes and Pigments vol 74 no 1 pp 108ndash1122007
[13] I Yavari R Amiri and M Haghdadi ldquoTriphenyphosphine-mediated efficient synthesis of functionalized 2-OXO-2H-Chromenesrdquo Phosphorus Sulfur and Silicon and the RelatedElements vol 179 no 11 pp 2163ndash2168 2004
[14] E Galariniotou V Fragos A Makri K E Litinas and D NNicolaides ldquoSynthesis of novel pyridocoumarins and benzo-fused 6-azacoumarinsrdquo Tetrahedron vol 63 no 34 pp 8298ndash8304 2007
Journal of Chemistry 5
[15] S D Kudale and M N Deodhar ldquoSynthesis and evaluationof some coumarin containing potential antimicrobial agentsrdquoJournal of Chemistry vol 9 no 4 pp 2493ndash2500 2012
[16] M A Hosny M A Radwan and E A El-Sawy ldquoSynthesis andanticancer activity of some new derivatives of coumarin andquinolinyl mercaptotriazolesrdquo Journal of Chemistry vol 9 no4 pp 1737ndash1745 2012
[17] D Kini andMGhate ldquoSynthesis and oral hypoglycemic activityof 3-[51015840-Methyl-21015840- aryl-31015840-(thiazol-21015840-yl amino) thiazolidin-41015840-one]coumarin Derivativesrdquo Journal of Chemistry vol 8 no1 pp 386ndash390 2011
[18] J L Du L I Li and D H Zhang ldquoUltrasound promotedsynthesis of 3-carboxycoumarins in aqueous mediardquo Journal ofChemistry vol 3 p 1 2006
[19] B Mohtat I Yavari R E Ameri and E Salahia ldquoSynthesisof aza coumarines by nucleophilic addition of acetylenic esterscatalysed by Ph
3PrdquoCroaticaChemicaActa vol 84 no 1 pp 123ndash
126 2011[20] B Mohtat S Azimzadeh H Djahaniani and L Pirhadi ldquoPh
3P
catalyzed synthesis of alkyl 2-(4-oxopyridin-1(4H)-Yl) acrylatesby nucleophilic addition to alkyl propiolatesrdquo South AfricanJournal of Chemistry vol 63 pp 204ndash206 2010
[21] B Mohtat Z N Azar S Nahavandian H Djahanianiand A Ahmadi ldquoSynthesis of dialkyl 2-(4-oxopyridin-1(4H)-yl)dicarboxylates through the reaction of 4-hydroxypyridineand dialkyl acetylenedicarboxylate in the presence of triph-enylphosphinerdquo Journal of the Mexican Chemical Society vol55 no 3 pp 194ndash196 2011
[22] B Mohtat S Nahavandian N Z Azar H Djahaniani andZ Hossaini ldquoTriphenylphosphine-promoted c-vinylation of 4-hydroxyquinolinesrdquo Zeitschrift fur Naturforschung vol 66 no7 pp 700ndash704 2011
Submit your manuscripts athttpwwwhindawicom
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Inorganic ChemistryInternational Journal of
Hindawi Publishing Corporation httpwwwhindawicom Volume 2014
International Journal ofPhotoenergy
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Carbohydrate Chemistry
International Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Chemistry
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Advances in
Physical Chemistry
Hindawi Publishing Corporationhttpwwwhindawicom
Analytical Methods in Chemistry
Journal of
Volume 2014
Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
SpectroscopyInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014
Medicinal ChemistryInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Chromatography Research International
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Applied ChemistryJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Theoretical ChemistryJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Spectroscopy
Analytical ChemistryInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Quantum Chemistry
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Organic Chemistry International
ElectrochemistryInternational Journal of
Hindawi Publishing Corporation httpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
CatalystsJournal of
4 Journal of Chemistry
N
O
N
H
N
OHO
OMe
H10
4
CO2Me
CO2Me
PPh3+
+
minus
CHCO2MePh3P+
MeO2C
MeO2C
minusPPh3
O
Scheme 4
ring at the ortho position relative to the strong activationgroup The product is presumablyproduced by intramolecu-lar lactonization of the unsaturated diester 10 (Scheme 4)
4 Conclusion
From the above results we conclude that treatment of oxygenatom of the pyran ring belongs to the starting phenolwhile the periselectivity in the construction of this new ringdepends on the higher reactivity of the free o-positions ofthe phenol during the aromatic electrophilic substitutionsequenceThese functionalised coumarinsmay be consideredas potentially useful synthetic intermediates because theypossess atoms with different oxidation states The advantagesof presentmethod are the fact that it performed under neutralcondition and substances are utilized in their basic formwith-out anymodificationThe simplicity of the present proceduremakes it an interesting alternative to other approaches
Acknowledgment
The authors thank the Karaj Branch Islamic Azad Universityfor support of this work
References
[1] R D Murray J Mendez and S A Brown The NaturalCoumarins Occurrence Chemistry and Biochemistry JohnWiley amp Sons 1982
[2] F A Jimenez-Orozco J A Molina-Guarneros N Mendoza-Patino et al ldquoCytostatic activity of coumarin metabolitesand derivatives in the B16- F10 murine melanoma cell linerdquoMelanoma Research vol 9 no 3 pp 243ndash247 1999
[3] G J Finn B Creaven and D A Egan ldquoStudy of the invitro cytotoxic potential of natural and synthetic coumarinderivatives using human normal and neoplastic skin cell linesrdquoMelanoma Research vol 11 no 5 pp 461ndash467 2001
[4] D Yim R P Singh C Agarwal S Lee H Chi and R AgarwalldquoA novel anticancer agent decursin induces G1 arrest and
apoptosis in human prostate carcinoma cellsrdquo Cancer Researchvol 65 no 3 pp 1035ndash1044 2005
[5] M E Riveiro R Vazquez A Moglioni et al ldquoBiochemi-cal mechanisms underlying the pro-apoptotic activity of 78-dihydroxy-4-methylcoumarin in human leukemic cellsrdquo Bio-chemical Pharmacology vol 75 no 3 pp 725ndash736 2008
[6] I Kostova S Raleva P Genova and R Argirova ldquoStructure-activity relationships of synthetic coumarins as HIV-1inhibitorsrdquo Bioinorganic Chemistry and Applications vol2006 Article ID 68274 9 pages 2006
[7] B FGage ldquoPharmacogenetics-based coumarin therapyrdquoHema-tology vol 2006 no 1 pp 467ndash473 2006
[8] D A Ostrov J A Hernandez Prada P E Corsino K AFinton N Le and T C Rowe ldquoDiscovery of novel DNA gyraseinhibitors by high-throughput virtual screeningrdquo AntimicrobialAgents and Chemotherapy vol 51 no 10 pp 3688ndash3698 2007
[9] R M Melavanki R A Kusanur M V Kulakarni and J SKadadevarmath ldquoRole of solvent polarity on the fluorescencequenching of newly synthesized 78-benzo-4-azidomethylcoumarin by aniline in benzene-acetonitrile mixturesrdquo Journalof Luminescence vol 128 no 4 pp 573ndash577 2008
[10] T Z Yu P Zhang Y L Zhao H Zhang J Meng andD W Fan ldquoSynthesis and photoluminescent properties oftwo novel tripodal compounds containing coumarin moietiesrdquoSpectrochimica Acta A vol 73 no 1 pp 168ndash173 2009
[11] H Turki S Abid S Fery-Forgues and R El Gharbi ldquoOpticalproperties of newfluorescent iminocoumarins part 1rdquoDyes andPigments vol 73 no 3 pp 311ndash316 2007
[12] X Li Y X Zhao T Wang M Q Shi and F P WuldquoCoumarin derivatives with enhanced two-photon absorptioncross-sectionsrdquo Dyes and Pigments vol 74 no 1 pp 108ndash1122007
[13] I Yavari R Amiri and M Haghdadi ldquoTriphenyphosphine-mediated efficient synthesis of functionalized 2-OXO-2H-Chromenesrdquo Phosphorus Sulfur and Silicon and the RelatedElements vol 179 no 11 pp 2163ndash2168 2004
[14] E Galariniotou V Fragos A Makri K E Litinas and D NNicolaides ldquoSynthesis of novel pyridocoumarins and benzo-fused 6-azacoumarinsrdquo Tetrahedron vol 63 no 34 pp 8298ndash8304 2007
Journal of Chemistry 5
[15] S D Kudale and M N Deodhar ldquoSynthesis and evaluationof some coumarin containing potential antimicrobial agentsrdquoJournal of Chemistry vol 9 no 4 pp 2493ndash2500 2012
[16] M A Hosny M A Radwan and E A El-Sawy ldquoSynthesis andanticancer activity of some new derivatives of coumarin andquinolinyl mercaptotriazolesrdquo Journal of Chemistry vol 9 no4 pp 1737ndash1745 2012
[17] D Kini andMGhate ldquoSynthesis and oral hypoglycemic activityof 3-[51015840-Methyl-21015840- aryl-31015840-(thiazol-21015840-yl amino) thiazolidin-41015840-one]coumarin Derivativesrdquo Journal of Chemistry vol 8 no1 pp 386ndash390 2011
[18] J L Du L I Li and D H Zhang ldquoUltrasound promotedsynthesis of 3-carboxycoumarins in aqueous mediardquo Journal ofChemistry vol 3 p 1 2006
[19] B Mohtat I Yavari R E Ameri and E Salahia ldquoSynthesisof aza coumarines by nucleophilic addition of acetylenic esterscatalysed by Ph
3PrdquoCroaticaChemicaActa vol 84 no 1 pp 123ndash
126 2011[20] B Mohtat S Azimzadeh H Djahaniani and L Pirhadi ldquoPh
3P
catalyzed synthesis of alkyl 2-(4-oxopyridin-1(4H)-Yl) acrylatesby nucleophilic addition to alkyl propiolatesrdquo South AfricanJournal of Chemistry vol 63 pp 204ndash206 2010
[21] B Mohtat Z N Azar S Nahavandian H Djahanianiand A Ahmadi ldquoSynthesis of dialkyl 2-(4-oxopyridin-1(4H)-yl)dicarboxylates through the reaction of 4-hydroxypyridineand dialkyl acetylenedicarboxylate in the presence of triph-enylphosphinerdquo Journal of the Mexican Chemical Society vol55 no 3 pp 194ndash196 2011
[22] B Mohtat S Nahavandian N Z Azar H Djahaniani andZ Hossaini ldquoTriphenylphosphine-promoted c-vinylation of 4-hydroxyquinolinesrdquo Zeitschrift fur Naturforschung vol 66 no7 pp 700ndash704 2011
Submit your manuscripts athttpwwwhindawicom
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Inorganic ChemistryInternational Journal of
Hindawi Publishing Corporation httpwwwhindawicom Volume 2014
International Journal ofPhotoenergy
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Carbohydrate Chemistry
International Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Chemistry
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Advances in
Physical Chemistry
Hindawi Publishing Corporationhttpwwwhindawicom
Analytical Methods in Chemistry
Journal of
Volume 2014
Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
SpectroscopyInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014
Medicinal ChemistryInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Chromatography Research International
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Applied ChemistryJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Theoretical ChemistryJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Spectroscopy
Analytical ChemistryInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Quantum Chemistry
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Organic Chemistry International
ElectrochemistryInternational Journal of
Hindawi Publishing Corporation httpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
CatalystsJournal of
Journal of Chemistry 5
[15] S D Kudale and M N Deodhar ldquoSynthesis and evaluationof some coumarin containing potential antimicrobial agentsrdquoJournal of Chemistry vol 9 no 4 pp 2493ndash2500 2012
[16] M A Hosny M A Radwan and E A El-Sawy ldquoSynthesis andanticancer activity of some new derivatives of coumarin andquinolinyl mercaptotriazolesrdquo Journal of Chemistry vol 9 no4 pp 1737ndash1745 2012
[17] D Kini andMGhate ldquoSynthesis and oral hypoglycemic activityof 3-[51015840-Methyl-21015840- aryl-31015840-(thiazol-21015840-yl amino) thiazolidin-41015840-one]coumarin Derivativesrdquo Journal of Chemistry vol 8 no1 pp 386ndash390 2011
[18] J L Du L I Li and D H Zhang ldquoUltrasound promotedsynthesis of 3-carboxycoumarins in aqueous mediardquo Journal ofChemistry vol 3 p 1 2006
[19] B Mohtat I Yavari R E Ameri and E Salahia ldquoSynthesisof aza coumarines by nucleophilic addition of acetylenic esterscatalysed by Ph
3PrdquoCroaticaChemicaActa vol 84 no 1 pp 123ndash
126 2011[20] B Mohtat S Azimzadeh H Djahaniani and L Pirhadi ldquoPh
3P
catalyzed synthesis of alkyl 2-(4-oxopyridin-1(4H)-Yl) acrylatesby nucleophilic addition to alkyl propiolatesrdquo South AfricanJournal of Chemistry vol 63 pp 204ndash206 2010
[21] B Mohtat Z N Azar S Nahavandian H Djahanianiand A Ahmadi ldquoSynthesis of dialkyl 2-(4-oxopyridin-1(4H)-yl)dicarboxylates through the reaction of 4-hydroxypyridineand dialkyl acetylenedicarboxylate in the presence of triph-enylphosphinerdquo Journal of the Mexican Chemical Society vol55 no 3 pp 194ndash196 2011
[22] B Mohtat S Nahavandian N Z Azar H Djahaniani andZ Hossaini ldquoTriphenylphosphine-promoted c-vinylation of 4-hydroxyquinolinesrdquo Zeitschrift fur Naturforschung vol 66 no7 pp 700ndash704 2011
Submit your manuscripts athttpwwwhindawicom
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Inorganic ChemistryInternational Journal of
Hindawi Publishing Corporation httpwwwhindawicom Volume 2014
International Journal ofPhotoenergy
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Carbohydrate Chemistry
International Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Chemistry
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Advances in
Physical Chemistry
Hindawi Publishing Corporationhttpwwwhindawicom
Analytical Methods in Chemistry
Journal of
Volume 2014
Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
SpectroscopyInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014
Medicinal ChemistryInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Chromatography Research International
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Applied ChemistryJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Theoretical ChemistryJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Spectroscopy
Analytical ChemistryInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Quantum Chemistry
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Organic Chemistry International
ElectrochemistryInternational Journal of
Hindawi Publishing Corporation httpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
CatalystsJournal of
Submit your manuscripts athttpwwwhindawicom
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Inorganic ChemistryInternational Journal of
Hindawi Publishing Corporation httpwwwhindawicom Volume 2014
International Journal ofPhotoenergy
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Carbohydrate Chemistry
International Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Chemistry
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Advances in
Physical Chemistry
Hindawi Publishing Corporationhttpwwwhindawicom
Analytical Methods in Chemistry
Journal of
Volume 2014
Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
SpectroscopyInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014
Medicinal ChemistryInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Chromatography Research International
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Applied ChemistryJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Theoretical ChemistryJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Spectroscopy
Analytical ChemistryInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Quantum Chemistry
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Organic Chemistry International
ElectrochemistryInternational Journal of
Hindawi Publishing Corporation httpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
CatalystsJournal of