N N NH N X Me N NNH2 O Me N NNHCXR O Me N N N O Me N S O Ph O N N O N NPh S O N O O Me N N N N R Me N N Me N N N Ar Me (2n) O O O O O O O O O O O S S Me Ph C6H4NO2-m C6H4NO2- p C6H4OMe- p C6H4Cl- p NH2 NHC6H4NO2-m NHC6H4OMe- p NH2 NHPh a b c d e f g h i j k l n R = CH CHPh 2 X NH 8a 8b R X = O 11 CH CHPh 9 6 NH CH CHPh 7 1 10 N NNHCOCH2Cl O Me CH2(CO2H)2 2 (2h, 2l) Heat H2NCXNH2 (2b) CH3CO2 – NH4 + H2NNHCSNH2 N NNHSO2C6H4Me- p O Me RCXY NaOEt –HY –H2O H+ H2NCMe X = S N N NH R O 2m ClCOCH2Cl 2o ClSO2C6H4Me- p (2g) NaOEt (2a-g) –H2O, 3a-g J.Chem. Research (S), 1997, 154–155 J. Chem. Research (M), 1997, 1041–1063 Synthesis and Biological Evaluation of Some New Fused Quinazoline Derivatives Salah S. Ibrahim, Ali M. Abdel-Halim, Yassien Gabr, Soummaia El-Edfawy and Reda M. Abdel-Rahman* Department of Chemistry, Faculty of Education, Ain-Shams University, Roxy, Cairo, Egypt We report that biologically active fused quinazolines have been synthesized via treatment of 3-(N-acyl/ aroylamino)quinazolin-4(3H)-ones (2) with various nucleophilic reagents; some of the products showed moderate antibacterial activity.The present work describes the synthesis of some new fused quinazolines starting from 3-(N-acyl/aroylamino)-2-methylquinazolin- 4(3H)-ones11 (2) and their antimicrobial activity in order to establish a relation between structure and reactivity. 2-Substituted pyrazolo[5,1-b]quinazolin-9(1H)-ones (3a–g) were obtained by refluxing 2 with sodium ethoxide (Scheme IA).Acylation of 3e followed by treatment with ammonium acetate–acetic acid13 afforded the heterocyclic system 5 (Scheme II). Also, 2-cinnamyl-5-methyl-s-triazolo[2,3-c]quinazoline (6) and 4-(4-chlorophenyl)-2,7-dimethyl[1,2,4,6]tetrazepino[ 2,3-c]quinazoline (7) were isolated from refluxing 2b with ammonium acetate–acetic acid and 2g with acetamidine hydrochloride in sodium ethoxide14 respectively. Investigations of the structure–activity relationships of 2h and 2l indicated that their activities are increased by fusion above their melting points to give 2-hydroxy/sulfanyl- 5-methyl-s-triazolo[1,5-c]quinazolines (8a,b).Interestingly, it was found that 2n on reaction with malonic acid in acetyl chloride15 produced 1-(2-methyl-4-oxoquinazolin-3-yl)-3 p h e n y l - 2 , 3 - d i - h y d r o - 2 - t h i o x o p y r i m i d i n e - 4 , 6 ( 1 H, 5H ) - d i o n e (10) which on refluxing with sodium ethoxide gave the pyrimido[ 3p,4p: 2,3]pyrazolo[5,1-b]quinazolinedione 11.The IR spectrum of 11 showed characteristic absorption bands at vmax 3194 (OH), 1692 (C�O), 2923 (CH2, CH3), 1316 (NCS) and 1109 cmµ1 (C·S). The mass spectrum of 11 showed loss of Ph and H2 to give a base peak at m/z 281. Isomeric structures 12 and 13 were obtained respectively from treatment of 2m with ammonium acetate–acetic acid and the interaction between 1 and chloroacetamide in N,N-dimethylformamide (DMF) (Scheme IB).The structures of 12 and 13 were deduced from their IR spectra which revealed bands at vmax 3404 (OH), 3277, 3130 (NH), 2977, 2871 (CH3, CH2), 1657 (C�O) and 1608 cmµ1 (cyclic C�C). The UV spectrum of 12 showed bands at lmax 320, 306, 266 and 255 nm. Bands of this type are found with all aromatic azo compounds.16 A convenient method for the synthesis of the fully fused quinazolines 17 was deduced from treatment of 2-methyl/ phenyl-4-(arylmethylidene)oxazol-5(4H)-ones (14a,b) with 1 followed by cyclocondensation via hydrazinolysis in basic media.The IR spectrum of 17 showed disappearance of the NH2, NH and C�O absorption bands, indicating the formation of a cyclic structure. 154 J. CHEM. RESEARCH (S), 1997 *To receive any correspondence. Scheme IAN N NH C6H4Cl- p O N N NH C6H4NO2- p O N N NH C6H4OMe- p O N N NH C6H4NO2- p O N N N C6H4Cl- p O N N N C6H4NO2- p O N N N C6H4OMe- p O N N N C6H4NO2- p O COCMe3 COCH2Cl CH2OH CH2 N N N N N C6H4NO2- p HCHO–piperidine–MeOH HCHO–MeOH ClCOCH2Cl ClCOCMe3 5 CH3CO2NH4 H+ 4b 3e 4a 3g 4c 3f 4d O 3e Measurements of the biocidal activity of some of the prepared compounds employing Cup-diffusion techniques17 showed that 16a is the most bactericidal and displays an effect18 equal to that of gentamycin towards E.coli. Techniques used: UV–VIS, IR, 1H NMR and mass spectroscopy; X-ray and elemental analysis References: 17 Table 1: Physical data for new compounds Schemes: 3 Charts: 4 (Fragmentation patterns of compounds 2g, 8a, 11 and 13) Received, 9th January 1996; Accepted 5th November 1996 Paper E/6/00184J References cited in this synopsis 11 P. Mishra, P. N. Gupta and A. K. Shakya, J. Indian Chem Soc., 1991, 68, 618. 14 R. M. Abdel-Rahman, Indian J. Chem., 1988, 27B, 548. 15 M. Seada, R. M. Abdel-Rahman and M. Abdel-Megid, Indian J. Heterocycl. Chem., 1993, 9. 16 O. H. Wheeler and P. H. Gore, J. Org. Chem., 1961, 26, 3298. 17 T. J. Mackie and J. E. MacCartheny, Practical Medical Microbiology, 30th edn., Churchill Livingstone, Edinburgh, London, New York, 1989. 18 S. A. Abdel-Aziz, H. A. Allimony, H. M. El-Shaaer, U. F. Ali and R. M. Abdel-Rahman, Phosphorus, Sulfur Silicon Relat. Elem., 1996, 113, 67. J. CHEM. RESEARCH (S), 1997 155 Scheme IB S