摘要:

6 J. CHEM. RESEARCH (S) 1999 A Novel and Efficient Method for the Synthesis of N-Arylsulfonylamino-2-pyridones Galal H. Elgemeie,*a Ahmed H. H. Elghandour,b Hosny A. Alib and Hassan M. Abdel-Azzezb abDepartment of Chemistry Faculty of Science Helwan University Helwan Cairo Egypt Department of Chemistry Faculty of Science Cairo University Beni-suef Cairo Egypt A novel and efficient method for the synthesis of N-arylsulfonylamino-2-pyridones via the reaction of N-cyanoacetohydrazides with ethyl arylidenecyanoacetate derivatives is investigated; N-sulfonated aminopyridines are also prepared from the reaction of N-amino-2-pyridones with arylsulfonyl chlorides. We report here a new one-step synthesis of N-sulfonated aminopyridine derivatives from the reaction of N-cyano- acetoarylsulfonyl hydrazides with ethylarylidenecyanoactate derivatives; the scope and limitation of our procedure for the synthesis of N-alkylated amino-2-pyridone derivatives is also discussed.Recently N-amino-2-pyridones have proved to be useful synthetic intermediates but there are very few synthetic procedures for the preparation of such compounds.1 Recent reports from our laboratory have demonstrated the eectiveness of a variety of N-substituted amino deriva- tives of pyridines and other antimetabolites are anti- neoplastic agents in a number of experimental murine tumour systems.2¡Ó4 Since these compounds have been shown to inhibit the incorporation of thymidine and uridine into DNA and RNA and appear to constitute a new class of HNNC NC NH2 O Ar1 ArSO2Cl NNH2 ¡VH2 Ar1 ArSO2Cl 2 pyridine CN O 11 (ref.13) CN EtOH/Plp. heat O N 1 EtO2C H2N EtO2C H2N NH2 14 Ar 10,11 Ar1 abcd 2a Ph b 4-H3C-C6H4 *To receive any correspondence. antimetabolites it was of interest to evaluate the eects of various structural modications on biological activity. To this end here we report the synthesis of novel N- sulfonylamino derivatives of 2-pyridones. Thus it has been found that cyanoacetohydrazide 1 reacts with arylsulfonyl chloride 2 in pyridine to aord the corresponding N-cyano- acetoarylsulfonylhydrazides 3 in good yields (Chart 1). Compounds 3 reacted with ethyl arylidenecyanoacetate in reuxing pyridine (6 h) to yield the N-arylsulfonylamino-2- pyridones 8. Each structure of 8 was established on the basis of elemental analysis and spectral data. Thus the mass spectrum of 8c was compatible with the molecular formula C20H14N4O4S (M 406) and 1H NMR spectrum contained two broad singlets at d 3.9 and 8.6 assignable to OH and NH groups respectively.The formation of 8 from 3 and 4 is assumed to proceed via addition of the active O Ar1 NC CN Ar1 OEt OS HNO O Ar EtO NH O NH O NH-SO2-Ar 5 EtOH/Plp. heat Ar1 Ar1 CN CN EtO2C N O N O H2N NH-SO NH-SO2-Ar 2-Ar CN NC CN O HO O 2 7 Ar1 NNH2 13 9Ar1 ONH NH 12 1 + 4 Ar1 3 EtO2C H2N NC EtO Ph 4-Cl-C6H4 4-H3CO-C6H4 4-NO2-C6H4 8,9 ghijkl f Ph 4-NO2-C6H4 CN 4 ¡VH2 pyridine/heat 8,9 Ar a Ph Ph b Ph 4-Cl-C6H4 c Ph 4-H3C-C6H4 d Ph 4-H3CO-C6H4 e Ph 4-(H3C)2N-C6H4 Chart 1 J. Chem. Research (S) 1999 6¡Ó7 J. Chem. Research (M) 1999 0141¡Ó0150 Ar1 NC CN pyridine/heat HO N O NH-SO2-Ar ¡VH2 NC CN HO O 6Ar1 NNH-SO2-Ar ArSO2Cl CN NC ¡VH2 HO O 8 Ar1 NNH2 10 Ar1 Ar 4-H3C-C6H4 Ph 4-H3C-C6H4 4-Cl-C6H4 4-H3C-C6H4 4-H3C-C6H4 4-H3C-C6H4 4-H3CO-C6H4 4-H3C-C6H4 4-(H3C)2N-C6H4 4-NO2-C6H4 4-H3C-C6H4Chart 2 methylene group of 3 to the double bond of 4 to give the in- termediate acyclic adduct 5.The Michael adduct 5 was cyclized via ethanol elimination to give the intermediate dihydropyridine derivatives 6 which are oxidized under the reaction conditions to yield the novel N-arylsulfonylamino- 2-pyridone derivatives 8. The course of the reaction between the N-cyanoacetylarylsulfonylhydrazides 3 and 4 prompted us to investigate this reaction between cyanoacetohydrazide 1 and 4 under the same conditions. The products obtained were shown to be formed by the same mechanism as that between 3 and 4 to give the N-amino-2-pyridones 10.5 The structures of compounds 10 were established on the basis of elemental analysis and spectral data.When 10 was stirred with arylsulfonyl chlorides in pyridine at room temperature for 24 h it gave the corresponding N-sulfonated pyridine 8. To investigate the scope of this reaction further we studied the reaction of 3 and 4 under other basic conditions. In con- trast it has been found that 3 reacted with 4 in re�uxing ethanol that contains catalytic amounts of piperidine to yield the corresponding 5-ethoxycarbonyl-N-arylsulfonyl- amino-2-pyridone derivatives 9 in good yields. The struc- J. CHEM. RESEARCH (S) 1999 7 tures of 9 were established and con®rmed for the reaction products on the basis of their elemental analysis and spec- tral data (MS IR and 1H NMR).The analytical data for 9g revealed a molecular formula C22H20N4O5S (Má 452); 1H NMR spectroscopy was used to con®rm this structure for the product. Thus 1H NMR revealed a triplet at d 0.612 assigned to a methyl ester group a quartet at d 3.79 assigned to a CH2 ester group and a broad singlet at d 9.2 assignable to an NH group. The mechanism of the reaction of 3 and 4 under these conditions is assumed to proceed through the formation of the initial acyclic adduct 5 which cyclises to the intermediate 7 and hence to the product 9. The reaction of cyanoacetohydrazide 1 and 4 and piperidine in re�uxing ethanol led to the reported ethyl N-amino-2- pyridone-5-carboxylate 11.5 When 11 was left to react with arylsulfonyl chlorides in pyridine at room temperature for 24 h the corresponding N-arylsulfonylamino-2-pyridones 9 was obtained in good yields.Similar to the behaviour of 3 towards 4 compounds 3 reacted with arylidene derivatives of benzoylacetonitrile (15) in re�uxing pyridine to yield the N-sulfonated pyridines 18 (Chart 2). The structures of 18 were established on the basis of their elemental analysis and spectral data. Thus structure 18i is supported by its mass spectrum which showed a molecular formula C26H18N4O3S (Má 466). 1H NMR spectroscopy was used to con®rm this structure for the products. Thus 1H NMR revealed a multiplet at d 7.35±8.65 assigned to the aromatic protons and a broad singlet at d 11.55 assigned to the NH proton. In summary we have achieved a regiospeci®c synthesis of interesting N-sulfonated aminopyridines by the reaction of cyanosulfonylhydrazides with a,b-unsaturated nitriles. Techniques used IR 1H NMR and mass spectrometry References 13 Charts 2 Received 16th January 1998; Accepted 29th September 1998 Paper E/8/00468D References cited in this synopsis 1 A. Hadi N. Martin C. Seoane and L. J. Soto J. Chem. Soc. 2 G. E. H. Elgemei A. M. Attia O. S. Farag and S. M. Sherif 3 G. E. H. Elgemeie and B. A. W. Hussain Tetrahedron 1994 50 4 G. E. H. Elgemeie A. M. Attia and N. M. Fathy Liebigs Ann. 5 M. R. H. El Moghayar A. A. El-Agamay N. M. Abed and Perkin Trans. 1 1993 1045. J. Chem. Soc. Perkin Trans. 1 1994 1285. 199. Chem. 1994 955. M. K. A. Ibrahim An. Quim. 1983 8

ISSN:0308-2342    

DOI:10.1039/a800468d

出版商:RSC    

年代:1999

数据来源: RSC