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1-Substituted 3-Dimethylaminoprop-2-en-1-ones as BuildingBlocks in Heterocyclic Synthesis: Routes to 6-Aryl- and6-Heteroaryl-2H-pyran-2-ones and 6- and4-Arylpyridin-2(1H)-ones

 

作者: Fatima Al-Omran,  

 

期刊: Journal of Chemical Research, Synopses  (RSC Available online 1997)
卷期: Volume 0, issue 3  

页码: 84-85

 

ISSN:0308-2342

 

年代: 1997

 

DOI:10.1039/a605368h

 

出版商: RSC

 

数据来源: RSC

 

摘要:

R Me O R NMe2 O N O O R¢ DMF, DMA 3 O R O R¢COHN 4 a R = Ph b R = 2-thienyl c R = 2-furyl d R = 2-pyridyl e R = 2-naphthyl f R = pyrrol-2-yl a R = R¢ = Ph b R = 2-thienyl, R¢ = Ph c R = 2-furyl, R¢ = Ph d R = 2-pyridyl, R¢ = Ph e R = 2-naphthyl, R¢ = Ph f R = pyrrol-2-yl, R¢ = Ph g R = Ph, R¢ = Me h R = 2-thienyl, R¢ = Me i R = 2-furyl, R¢ = Me j R = 2-naphthyl, R¢ = Me 8 4a–f 5 R NMe2 CN CN O O NMe2 CN NH2 R NH2 O NC R NMe2 NH O R NC CN R NC NMe 9 10 CN CH2 X X = CN X = CONH2 11 13 12 4a–c 9–13a R = Ph b R = 2-thienyl c R = 2-furyl J.Chem. Research (S), 1997, 84–85 J. Chem. Research (M), 1997, 0601–0615 1-Substituted 3-Dimethylaminoprop-2-en-1-ones as Building Blocks in Heterocyclic Synthesis: Routes to 6-Aryland 6-Heteroaryl-2H-pyran-2-ones and 6- and 4-Arylpyridin- 2(1H)-ones Fatima Al-Omran,* Nouria Al-Awadhi, Mervat Mohammed Abdel Khalik, Kamini Kaul, Abdel Abu EL-Khair and Mohammed Hilmy Elnagdi* Department of Chemistry, Faculty of Science, University of Kuwait, PO Box 5969, Safat 13060, Kuwait Several new 6-substituted-3-acylamino-2H-pyran-2-ones 6a–j have been prepared from the reaction of enaminones 4a–f with N-acyl- and N-benzoyl-glycines; the enaminones 4a–c react with malononitrile in ethanol solution and in the presence of a base to yield amides 11a–c which are converted into 6-aryl-1,2-dihydro-2-oxypyridine-3-carbonitriles 13a–c on reflux in acetic acid.In conjunction with our interest in the synthesis of functionally substituted heteroaromatic compounds as potential pharmaceuticals,7–10 the development of an efficient route for the synthesis of 6-aryl- and 6-heteroaryl-2H-pyran-2-ones as potential anti-HIV agents seemed interesting.Recently Kocevar and co-workers12–14 have described a one-pot synthesis of 3-acylaminopyranones by mixing 1,3-dicarbonyl compounds, triethyl orthoformate or dimethylformamide dimethyl acetal and N-acylglycines with a large excess of acetic anhydride.Since this method seemed the simplest way to synthesise our required compounds we investigated the reaction of hippuric acid, dimethylformamide dimethyl acetal and the methyl ketones 3a–f. However, under these conditions only oily mixtures of products were obtained. We thus decided to modify this synthetic approach by first condensing 3a–f with dimethylformamide dimethyl acetal, utilizing a literature procedure for the synthesis of 4a from 3a15 and reacting the produced 1-substituted 3-dimethylaminoprop- 2-en-1-ones 4a–c,e with N-acylglycines.We found that 4a reacts with hippuric acid in refluxing acetic anhydride to yield a product of molecular formula C18H13NO3 which can be formulated as the oxazolone derivative 7a or the pyranone 8a. Structure 8a was established for this product based on the 1H NMR spectrum which revealed an absence of any signals for sp3 carbons at d 3.0–5.0 but showed two doublets at d 7.16 and 8.22 for the pyranone 5-H and 4-H, respectively.Similarly the reaction of 4b–f with hippuric acid afforded the pyranones 8b–f. When 4a–c,e were refluxed with glycine in the presence of acetic anhydride the pyranones 8g–j were obtained in good yields. It is assumed that acetyl glycine generated in situ is cyclised into 5b which then reacts with 4a–c,e yielding the final isolable 8g–j. The 1H NMR spectra of all compounds 8a–j revealed characteristic doublets for 4-H and 5-H with J=8 Hz. The formation of 8a-j from 4a–f with either N-acylglycines or hippuric acid can thus be considered as an extension of the Kepe pyranone synthesis12–14 to enable the synthesis of 6-aryl- and 6-heteroaryl-pyran- 2-ones.Compounds 4a–c reacted with malononitrile in ethanol and in the presence of a base, affording 1:1 adducts. We first assigned the pyran structures 10a–c for these products, by assuming initial formation of the Michael adducts 9a–c and subsequent cyclization. However, the 1H NMR spectrum for compound 11b, for example, revealed a two-proton doublet at d 5.77 and 7.23 with a J value of 13 Hz which can be only attributed to trans olefinic protons.We therefore considered structures 11a–c for these reaction products. They are assumed to be formed via initial hydrolysis of malononitrile to cyanoacetamide by water present in the solvent. This was followed by condensation of the active methylene group with the carbonyl of compounds 4a–c. Water eliminated in the reaction then hydrolyses a further amount of malononitrile and the reaction can thus proceed to completion.This structure was confirmed by preparing the same reaction products via condensation of cyanoacetamide with 4a–c under the same reaction conditions. Furthermore, compounds 11a–c were converted into the pyridinones 13a–c which were also obtained by hydrolysis of 3 - a r y l - 2 - c y a n o - 5 - d i m e t h y l a m i n o - 2 , 4 - p e n t a - 2 , 4 - d i e n e n i t r i l e s 12a–c by the action of acetic acid–hydrochloric acid mixture.Attempts to prepare 11a–c by direct hydrolysis of 12a–c, recently obtained in our laboratory,21 in ethanol–piperidine for 24 h, failed, thus supporting the assumption that cyanoacetamide and not malononitrile is the reactive species in this reaction. 84 J. CHEM. RESEARCH (S), 1997 *To receive any correspondence.R O NMe2 HN O CN R CN CONH2 14 4a,b NaOEt a R = Ph b R = 2-thienyl In contrast to the observed formation of the pyridinones 13a–c, treatment of 4a,b with cyanoacetamide in sodium ethoxide solution afforded the pyridinones 14a,b.This work was financed by University of Kuwait Research grants SC 055 and SC 071. We are grateful to the general facility projects at the Chemistry Department, Faculty of Science, University of Kuwait, for analytical and spectral measurements. Techniques used: IR, 1H and 13C NMR, mass spectrometry References: 21 Received, 31st July 1996; Accepted, 10th December 1996 Paper E/6/05368H References cited in this synopsis 7 H.Al-Awadhi, F. Al-Omran, M. H. Elnagdi, L. Infants, C. Foces- Foces, N. Jagerovic and J. Elguero, Tetrahedron, 1995, 51, 12 745. 8 M. H. Elnagdi, A. H. Elghandour, M. K. A. Ibrahim and I. S. A. Hafiz, Z. Naturforsch., 1992, 476, 572. 9 F. A. Abou-Shanab, M. H. Elnagdi, F. M. Ali and B. J. Wake- field, J. Chem. Soc., Perkin Trans. 1, 1994, 1449. 10 M. H. Elnagdi and A. W. Erian, Arch. Pharm. (Weinheim, Ger.), 1991, 324, 853. 11 J. D. Hepworth, in Comprehensive Heterocyclic Chemistry, ed. A. R. Katritzky and C. W. Rees, Pergamon Press, Oxford, 1984, vol. 3, pp. 737–883. 12 V. Kepe, M. Kocevar and S. Polance, Heterocycles, 1995, 41, 1299. 13 M. Kocevar, S. Polance, B. Vercek and M. Tisler, Liebigs Ann. Chem., 1990, 501. 14 V. Kepe, M. Kocevar, S. Polance, B. Vercek and M. Tisler, Tetrahedron, 1990, 46, 1081. 15 S. Tseng, J. W. Epstein, H. J. Brbander and G. Francisco, J. Heterocycl. Chem., 1987, 24, 837. 16 A. A. Elagamey, F. M. A. El Taweel, S. Z. A. Sowellium, M. A. Sofan and M. H. Elnagdi, Collect. Czech. Chem. Commun., 1990, 55, ???. 17 M. H. Elnagdi, R. M. Abdel-Motaleb, M. Mustafa, M. F. Zayed and E. M. Kamel, J. Heterocycl. Chem., 1987, 24, 1677. 28 C. P. Dell, T. J. Howe and W. C. Prowe, J. Heterocycl. Chem., 1994, 31, 749. 19 B. J. N. Martin, A. Martinez-Grau and C. Seoane, J. Heterocycl. Chem., 1995, 32, 1381. 20 N. M. Abed, N. S. Ibrahim and M. H. Elnagdi, Z. Naturforsch., 1986, 416, 925. 21 F. Al-Omran, M. M. Abdel Khalik and M. H. Elnagdi, Heteroatom Chem., 1995, 6, 545. J. CHEM. RESEARCH (S), 1997 85

 



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