Synthesis and Ab Initio Study of Pyrano[2,3-d]pyrimidine Derivatives

Document Type: Research Article


Department of Chemistry, Tehran North Branch, Islamic Azad University, Tehran, P.O. Box 191367-4711 Tehran, I.R. IRAN


Tetrahydrobenzo[b]pyran derivatives 1 were utilized for the synthesis of several new pyrano[2,3-d]pyrimidine derivatives 2. Compound 2 was obtained in the presence of Ac2O/H2SO4 (as a catalyst) and was confirmed by spectroscopic data such as IR, 1H NMR and 13C NMR. Ab initio calculation was carried out to study geometric optimization, thermodynamic parameters, aromaticity and dynamic process of conformational analysis for compound 2.


Main Subjects

[1] Karnik A.V., Kulkarin A.M., Malviya N.J., Mourya B.R., Jadhav B.L., Synthesis and In Vitro Anti-Bacterial Evaluation of Tetracyclic-Ortho-Fused 4H-Naphtho[1',2'-5,6]Pyrano[3,4-d](1,2,3)Selenadiazole and Its Derivatives, European Journal of Medicinal Chemistry., 43, p. 2615 (2008).

[2] Kwak J.H., Kang H.E., Jung J.K., Kim H.J., Cho J., Lee H., Synthesis of 7-Hydroxy-4-Oxo-4H-Chromene- and 7-Hydroxychroman-2-Carboxylic Acid N-Alkyl Amides and Their Antioxidant Activities, Archives of Pharmacal Research.,29, p. 728 (2006).

[3] Su C.R., Yeh S.F., liu C.M., Damu A.G., Kuo T.H., Chiang P.C., Bastow K.F., Lee K.H., Wu T.Sh., Anti-HBV and Cytotoxic Activities of PyranocoumarinDerivativesAnti-HBV and Cytotoxic Activities of Pyranocoumarin Derivatives., Bioorganic Medicinal Chemistry., 17, p. 6137 (2006).

[4] Chen Q., Zhu X., Jiang L., Yang M.L., FU G., Synthesis, Antifungal Activity and CoMFA Analysis of Novel 1,2,4-Triazolo[1,5-a]Pyrimidine Derivatives., European Journal of Medicinal Chemistry., 43, p. 595 (2008).

[5] Cecile G., Douguet D., Huteau V., Gilles M., Helene M.L., Sylvier P., Substituted Benzyl-Pyrimidines Targeting Thymidine Monophosphate Kinase of Mycobacterium Tuberculosis: Synthesis and In Vitro Anti-Mycobacterial Activity., Bioorganic Medicinal Chemistry.,16, p. 6075 (2008).

[6] Lin R., Sigmond G., Johnson P.J., Connolly S.K., Wetter E., Binnun T.V., Hughes W. V., Murray N. B.,Pandey S.J., Mazza M. M., Adams A.R., Pesquera F., Steven A.M., Synthesis and Evaluation of 2,7-diamino-thiazolo[4,5-d] pyrimidine Analogues as Anti-Tumor Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitors., Bioorganic Medicinal Chemistry Letters., 19, p. 2333 (2009).

[7] Deshmukh M.B., Salunkhe S.M., Patil D.R., Anbhule P.V., A Novel and Efficient one Step Synthesis of 2-Amino-5-Cyano-6-Hydroxy-4-Aryl Pyrimidines and Their Anti-Bacterial Activity.,European Journal of Medicinal Chemistry.,44, p. 2651 (2009).

[8] Rashad A.E., Hegab M.I., Adel-Megeid R.E., Fathalla N., Abdel-Megeid F.M.E., Synthesis and Anti-HSV-1 Evaluation of Some Pyrazoles and Fused Pyrazolopyrimidines., European Journal of Medicinal Chemistry., 44, p. 3285 (2009).

[9] Bruno O., Shenone S., Ranise A., Bondavalli F., Fillippelli W., Falcone G., Motola G., Mazzeo F., Antiinflammatory Agents: New Series of N-Substituted Amino Acids with Complex Pyrimidine Structures Endowed with Antiphlogistic Activity., II Farmaco., 54, p. 95 (1999).

[10] Sabry N.M., Mohamad H.M., Kattab E.S.A.E.H., Motlaq S.S., Synthesis of 4H-Chromene, Coumarin, 12H-Chromeno[2,3-d]Pyrimidine Derivatives and Some of Ttheir Antimicrobial and Cytotoxicity Activities., European Journal of Medicinal Chemistry., 46, p. 765 (2011).

[11] Nahas N.M., Adel Hafez A.A., A Simple and Efficient Synthesis of Fused Heterocyclic Quinoline Derivatives., Heterocyclic Communications.,13, p. 381 (2007).

[12] Bigdeli M.A., Moradi Sh., Nemati F., Ab initio Study of Atropisomers of 1,8-di-Pyridine 9H-Fluorene, Dibenzo[b,d]Furan, 9H-Cabazole and Dibenzo [b,d]Thiophene., Journal of Molecular Structure., 860, p. 64 (2008).

[13] Branowska D., Karczmarzyk Z., Rekowski A., Wysocki W., OlenderEwa., Urbanczyk-Lipkowska. Z.,Kalicki P., Structural Characterization of 6,6′-Bis(Substituted)-5,5′-bi-1,2,4-Triazines as Potential N-Heterocyclic Ligands for the Extraction of Nuclear Waste., Journal of Molecular Structure.,979, p. 186 (2010).

[14] Bigdeli M.A., Moradi Sh., Nemati F., Ab-Initio Study of Atropisomers of Some Derivatives of
1,8-Disubstituted Biphenylenes and Naphthalenes
., Journal of Molecular Structure.,807, p. 125 (2007).

[17] Frisch M.J., Trucks G.W., Schlegel H.B., Scuseria G.E., Robb M.A., Cheeseman J.R., Montgomery J.A., Vreven T., Kudin K.N., Burant J.C., Millam J.M., Iyengar S.S., Tomasi J., Barone V., Mennucci B., Cossi M., Scalmani G., Rega N., Petersson G.A., Nakatsuji H., Hada M., Ehara M., Toyota K., Fukuda R., Hasegawa J., Ishida M., Nakajima T., Honda Y., Kitao O., Nakai H., Klene M., Li X., Knox J.E., Hratchian H.P., Cross J.B., Bakken V., Adamo C., Jaramillo J., Gomperts R., Stratmann R.E., Yazyev O., Austin A.J., Cammi R., Pomelli C., Ochterski J.W., Ayala P.Y., Morokuma K., Voth G.A., Salvador P., Dannenberg J.J., Zakrzewski V.G., Dapprich S., Daniels A.D., Strain M.C., Farkas O., Malick D.K., Rabuck A.D., Raghavachari K., Foresman J.B., Ortiz J.V., Cui Q., Baboul A.G., Clifford S., Cioslowski J., Stefanov B.B., Liu G., Liashenko A., Piskorz P., Komaromi I., Martin R. L., Fox, D. J., Keith, T., Al-Laham, M. A., Peng, C. Y., Nanayakkara, A., Challacombe, M., Gill, P. M. W., Johnson, B., Chen, W., Wong, M. W., Gonzalez, C., Pople, J. A., Gaussian Inc., Wallingford CT, (2003).

[18] Buhl M., van Wullen C., Geometries and Electronic Structure of Extractable C90 Fullerenes., Chemical Physics Letters., 247, p. 63 (1995).

[19] Schleyer P.V.R., Maerker C., Dransfeld A., Jiao H., Van EikemaHommea N.J.R., Nucleus- Independent Chemical Shifts: a Simple and Efficient Aromaticity Probe., Journal of American Chemical Society., 118, p. 6317 (1996).

[20] Mobinikhaledi A., Foroughifar N., BodaghiFard M.A., Eco-Friendly and Efficient Synthesis of Pyrano[2,3-d]Pyrimidinone and Tetrahydrobenzo[b] Pyran Derivatives in Water, Synthesis and Reactivity in Inorganic, Metal-Organic and Nano-Metal Chemistry., 40, p. 179 (2010).

[21] Balalaie S., Bararjanian M., Sheikh-Ahmadi M., Hekmat Sh., Salehi P., Diammonium Hydrogen Phosphate; an Efficient and Versatile Catalyst for One-Pot Synthesis of Tetrahydrobenzo[b]Pyran Derivatives in Aqueous Media, Synthetic Communications., 37, p. 1097 (2007).

[22] Jiao H., Schleyer P.V.R., Aromaticity of Pericyclic Reaction Transition Structures: Magnetic Evidence, Journal of Physical Organic Chemistry., 11, p. 655 (1998).

[23] Schleyer P.V.R., Kiran B., Simion D.V., Sorensen T.S.,Does Cr(CO)3Complexation Reduce the Aromaticity of Benzene?., Journal of American Chemical Society., 122, p. 510 (2000).

[24] Badri Z., Pathak Sh., Flieg H., Rashidi-Ranjbar P., Bast R., Marek R., Foroutan-Nejad C., Ruud K., All-Metal Aromaticity: Revisiting the Ring Current Model Among Transition Metal Clusters., Journal of Chemical Theory and Computation., 9, p. 4789 (2013).