untitled European Journal of Chemistry 2 (2) (2011) 158‐162 European Journal of Chemistry ISSN 2153‐2249 (Print) / ISSN 2153‐2257 (Online)  2011 EURJCHEM DOI:10.5155/eurjchem.2.2.158‐162.381 European Journal of Chemistry Journal homepage: www.eurjchem.com Synthesis, antifungal activity and semi‐empirical AM1‐MO calculations of some new 4‐oxo‐4H‐chromene derivatives Hafez Mohamed El‐Shaaer, Salah Abdel‐Ghaffar Abdel‐Aziz, Faten Ismail Hanafy, Tarik El‐Sayed Ali* and Ali Zaky El‐Fauomy Department of Chemistry, Faculty of Education, Ain Shams University, Roxy, 11711, Cairo, Egypt *Corresponding author at: Department of Chemistry, Faculty of Education, Ain Shams University, Roxy, 11711, Cairo, Egypt. Tel.: +2.010.3730144; fax: +2022581243. E‐mail address: tarik_elsayed1975@yahoo.com (T.E. Ali). ARTICLE INFORMATION ABSTRACT Received: 01 January 2011 Received in revised form: 06 February 2011 Accepted: 09 February 2011 Online: 30 June 2011 KEYWORDS Some new antifungal agents have been prepared through reaction of 4‐oxo‐4H‐chromene‐3‐ carbaldehydes (1a,b) with some active primary amines (2a‐e) and amides/thioamides (6a‐d) in different conditions. Structures of the products were established on the basis of elemental analysis, IR, 1H NMR, mass spectra and semi‐empirical AM1‐MO calculations. Synthesis Chromone Chromone Derivatives 3‐Formylchromones Antifungal Activity AM1‐MO Calculation 1. Introduction Derivatives of 4H‐1‐benzopyran‐4‐one, also known as 4H‐ chromen‐4‐ones or chromones, belong to an important class of natural oxygen‐containing heterocycles that are widely distributed among many plants [1]. Many natural and synthetic chromone derivatives exhibit various types of biological activities [2] and find use as valuable synthetic intermediates in the preparation of pharmacologically relevant products and new heterocyclic systems [3‐5]. In recent years, 3‐ formylchromones have attracted considerable attention as highly reactive compounds, which can serve as the starting materials in synthesis of a whole series of heterocycles with useful properties due to three strong electrophilic centres (carbon atoms C‐2 and C‐4 of the chromone system and formyl group) [6]. These compounds possess a highly polarized C2‐C3 ‐bond and their reactions with dinucleophiles start predominantly from the attack of the unsubstituted C‐2 atom (1,4‐addition) and are accompanied by pyrone ring opening to form the ‐dicarbonyl intermediate capable of undergoing intramolecular heterocyclizations [7,8]. In continuation to our interest in the chemistry of 4‐oxo‐4H‐chromene‐3‐ carbaldehydes ring system [9‐14], owing to its considerable biological activities. The present work describes the preparation of new systems derived from the reaction of 4‐oxo‐ 4H‐chromene‐3‐carbaldehydes 1a,b with primary amines 2a,e and amide/thioamide derivatives 6a‐d in polar and non‐polar solvents. The antifungal activities for some the prepared compounds were investigated. Also, the AM1 molecular orbital calculations for some new compounds were studied and compared with their experimental 1H NMR values. 2. Experimental 2.1. Instrumentation The melting point was determined in an open capillary tube on a digital Stuart SMP‐3 apparatus. Infrared spectra were measured on Perkin‐Elmer 293 spectrophotometer (cm‐1), using KBr disks. 1H NMR spectra were measured on Gemini‐200 spectrometer (200 MHz), using DMSO‐d6 as a solvent and tetramethylsilane (TMS) (δ) as the internal standard. Mass spectra recorded on a Gas Chromatographic GCMSqp 1000 ex Shimadzu instrument at 70 eV. Elemental microanalyses were performed in microanalysis center at Cairo University. The purity of the synthesized compounds was checked by thin layer chromatography (TLC). 4‐Oxo‐4H‐chromene‐3‐carbaldehydes 1a,b, primary amines 2d‐e and amide 6b‐c were prepared by published methods: 1a,b [15], 2d [16], 2e [17], 6b [18], 6c [19]. 2.2. Synthesis 2.2.1. 3‐(Aryliminomethyl)‐4‐oxo‐4H‐chromenes (3a,d,e) A mixture of 4‐oxo‐4H‐chromene‐3‐carbaldehydes 1a,b (10.00 mmol) and amino compounds namely 1,4‐ phenylenediamine (2a), 4‐amino‐5‐methyl‐3‐thioxo‐1,2,4‐ triazole (2d) and 4‐amino‐6‐methyl‐3‐thioxo‐1,2,4‐triazin‐ 5(2H)‐one (2e) (10.00 mmol) in absolute ethanol or dry benzene (50 cm3) containing of 4‐toluenesulfonic acid (0.01 g) was refluxed for 5 h. The obtained solids were filtered off and crystallized to give 3a,d,e, respectively. El‐Shaaer et al. / European Journal of Chemistry 2 (2) (2011) 158‐162 159 Scheme 1 2.2.2. 3‐(Aryliminomethyl)‐4‐oxo‐4H‐chromenes (3b,c) A mixture of 1a (2.08 g, 10.00 mmol) and 2‐furfurylamine (2b) or 4‐aminoantipyrine (2c) (2.03 g, 10.00 mmol) in dry benzene (50 cm3) containing 4‐toluenesulfonic acid (0.01 g) was refluxed for 5 h. The obtained solids were filtered off and crystallized to give 3b,c, respectively. 2.2.3. 4‐[(2‐(Butylthio)‐6‐methyl‐4‐oxo‐2H‐chromen‐3(4H)‐ ylidene)methylamino]‐1,2‐dihydro‐1,5‐dimethyl‐2‐phenyl‐ pyrazol‐3‐one (4c) A mixture of 3c (3.73 g, 10.00 mmol) and 1‐butanethiol (0.9 g, 10.00 mmol) in dry toluene (50 cm3), was refluxed for 2 h. The solution so obtained was concentrated to half volume. The obtained solid was filtered off and crystallized to give 4c. 2.2.4. 3‐[(Arylamino)methylene]‐2‐ethoxy‐2,3‐dihydro‐6‐ methylchromen‐4‐ones (5b,c) Method A: A mixture of 1a (2.08 g, 10.00 mmol) and 2‐ furfurylamine (2b) or 4‐aminoantipyrine (2c) (10.00 mmol) in absolute ethanol (50 cm3) was refluxed for 5 h. The obtained solids were filtered off and crystallized to give 5b,c, respectively. Method B: A compound 3b,c (3.73 g, 10.00 mmol) were boiled in absolute ethanol (50 cm3) for 5 h. The obtained solids were filtered off and crystallized to give 5b,c, respectively. 2.2.5. 3‐[(Arylamino)methylene]‐2‐ethoxy‐2,3‐dihydro‐6‐ methylchromen‐4‐ones (7a‐c) A mixture of 1a (2.08 g, 10.00 mmol) and amide compounds namely 2‐cyanoacetamide (6a), 4‐chlorobenz‐ ylidene‐semicarbazone (6b) and 2‐amino‐4H‐chromen‐3‐ carboxamide (6c) (10.00 mmol) in absolute ethanol (50 cm3) was refluxed for 5 h. The obtained solids were filtered off and crystallized to give 7a‐c, respectively. 2.2.6. 3‐(N‐Aroylamino‐1‐hydroxymethyl)‐6‐methyl‐ chromen‐4‐ones (8a,c) Equimolar amounts of 1a (2.08 g, 10.00 mmol) and amide derivatives namely 2‐cyanoacetamide (6a), 2‐amino‐4H‐ chromen‐3‐carboxamide (6c) (10.00 mmol) in dry benzene (50 cm3) containing 4‐toulenesulfonic acid (0.01 g) were refluxed for 5 h. The obtained solids were filtered off and crystallized to give 8a,c, respectively. 2.2.7. 1‐(4‐chlorobenzylidene)‐4‐(2‐hydroxy‐6‐methyl‐4‐oxo‐ 2H‐chromen‐3(4H)‐ylidene)methyl)thiosemicarbazide (9d) Equimolar amounts of 1a (2.08 g, 10.00 mmol) and 4‐ chlorobenzylidenethiosemicarbazone (6d) (2.13 g, 10.00 mmol) in dry benzene (50 cm3) containing 4‐toulenesulfonic acid (0.01 g) was refluxed for 5 h. The obtained solid was filtered off and crystallized to give 9d. 160 El‐Shaaer et al. / European Journal of Chemistry 2 (2) (2011) 158‐161 Table 1. Physical properties and mass spectral data of newly prepared compounds. Comp. Formula M.p. (°C) Yield (%) Calc./Found% M. Wt MS, m/z (Ir/%) C H 3a C16H11N2O2Cl 203 ‐205 61 64.33 64.38 3.71 3.54 298.73 ‐ 3b C16H13NO3 201 ‐203 25 71.90 71.64 4.90 4.64 267.29 267 (M+, 28.90%), 186 (31.60), 174 (11.50), 172 (76.20), 160 (7.90), 135 (22.70), 134 (10.8), 109 (3.6), 108 (25.90), 107 (44.4), 91 (100), 82 (9.1), 81 (80.3), 78(15.1), 69 (94.50), 53 (71.8) 3c C22H19N3O3 219 ‐221 45 70.76 70.14 5.13 4.89 373.41 373 (M+, 9.20), 372 (35.60), 371 (92.90), 343 (12.20), 187 (18.60), 186 (100), 160 (57.40), 135 (20.70), 77 (26.60) 3d C14H12N4O2S 223 ‐225 66 55.99 55.63 4.03 4.83 300.34 301 (M+1, 0.23), 300 (M+, 0.44), 186 (40.20), 135 (12.00), 134 (17.91), 115 (100), 91 (13.7), 78 (23.07), 77 (30.13) 3e C15H12N4O3S 229 ‐230 75 54.87 54.51 3.68 3.52 328.35 330 (M+2, 5.60), 329 (M+1, 20.90), 328 (M+, 8.30), 186 (95.1), 160 (9.70), 143 (100), 134 (11.20), 115 (6.90), 102 (7.90), 91 (6.60), 84 (2.70), 52 (2.60) 4c C26H29N3O3S 185 ‐187 31 67.36 67.13 6.30 6.21 463.60 389 (M‐S(CH2)2CH3, 73.5), 373 (29.50), 297 (41.70), 281 (35.10), 214 (6.90), 201 (3.20), 188 (19.40), 187 (7.20), 186 (3.10), 160 (2.40), 121(19.00), 119 (3.90), 91 (2.30), 56 (100) 5b C18H19NO4 87 ‐88 30 68.99 68.84 6.11 5.66 313.35 ‐ 5c C24H25N3O4 197 ‐199 35 68.72 68.52 6.00 5.86 419.48 421 (M+2, 0.35), 391 (0.23), 373 (M‐EtOH, 10.40), 281 (23.02), 203 (44.36), 188 (9.10), 187 (5.08), 121 (10.54), 119 (3.78), 84 (42.09), 83 (15.43), 56 (100) 7a C16H16N2O4 204 ‐205 47 63.99 63.62 5.37 4.98 300.31 ‐ 7b C21H20N3O4Cl 244 ‐246 31 60.94 60.74 4.87 4.69 413.86 371 (M‐HCNO, 13.20), 245 (7.40), 228 (4.10), 186 (67.70), 185 (9.70), 134 (100), 95 (27.70), 91 (8.60), 77 (16.80), 51 (12.20) 7c C23H20N2O5 261 ‐262 40 68.31 68.26 4.98 4.96 404.42 358 (M‐EtOH, 31.2), 189 (100), 188 (2.70), 174 (16.80), 173 (98.90), 172 (13.10), 146 (18.20), 145 (20.30), 118 (29.20), 90 (20.30), 89 (37.00), 88 (5.80), 63 (27.00) 8a C14H12N2O4 222 ‐224 43 61.76 61.55 4.44 4.27 272.26 272 (M+, 3.40), 255 (15.20), 254 (11.80), 229 (24.10), 188 (47.30), 187 (18.90), 186 (100), 160 (13.90), 134 (25.80), 91 (10.60), 78 (11.90), 77 (22.20), 68 (11.90), 53 (6.50) 8c C21H16N2O5 190 ‐192 28 67.02 67.70 4.28 4.56 376.37 ‐ 9d C19H16N3O3SCl 210 ‐213 25 56.78 56.86 4.01 4.09 401.87 406 (M+4, 70.00), 368 (69.41), 338 (4.71), 305 (17.65), 274 (25.29), 260 (35.20), 238 (27.08), 220 (30.00), 203 (54.12), 178 (100), 176 (45.20), 113 (3.53) 3. Results and discussion 3.1. Chemistry Condensation reactions of Equimolar quantities of 4‐oxo‐ 4H‐chromene‐3‐carbaldehydes 1a,b with active primary amines namely, 1,4‐phenylenediamine (2a), 4‐amino‐5‐methyl‐ 3‐thioxo‐1,2,4‐triazole (2d) and 4‐amino‐6‐methyl‐3‐thioxo‐ 1,2,4‐triazin‐5(2H)one (2e) in ethanol and/or dry benzene containing 4‐toluenesulfonic acid as a catalyst yielded 3‐ (aryliminomethyl)‐4‐oxo‐4H‐chromenes 3a,d,e, respectively (Scheme 1). Similarly, reaction of 1a with 2‐furfurylamine (2b) and 4‐aminoantipyrine (2c) in dry benzene containing 4‐toluenesulfonic acid gave 3‐(aryliminomethyl)‐4‐oxo‐4H‐ chromene derivative 3b,c, respectively, but when 1a reacted with 2b,c in boiling ethanol yielded 1,4‐adducts 5b,c, respectively (Scheme 1). Reaction of 3c with nucleophilic reagents gave 1,4‐adducts due to 1,4‐addition of nucleophilic reagent. Thus, reaction of 3c with 1‐butanethiol in dry toluene gave 4c, and when 3b,c were refluxed in absolute ethanol gave 5b,c (Scheme 1). Structure of products 3a‐e, 4c and 5b,c were confirmed by elemental analysis, IR, 1H NMR and mass spectra (Table 1 and 2). The 1,4‐adducts 5b,c were formed by condensation of aldehyde 1a with primary amines 2b,c followed by 1,4‐addition of ethanol as nucleophile. In addition, 1H NMR spectra of 5b,c support the presence of H‐2 hydrogen atom on pyranone system not on pyrone system. The reason for this rather unusual ring‐addition of ethanol to give 1,4‐ adducts 5b,c was the formation of the stable hydrogen‐bonded ketoamine system [20]. On the other hand, condensation of aldehyde 1a with primary amines 2a,d,e gave only condensation products 3a,d,e and not gave 1,4‐adducts with addition of ethanol because the primary amines 2a,d,e are more basic amines in comparison with the amines 2b,c and their basicity are sufficiently to deprotonated the 1,4‐adducts and initiate the elimination of ethanol to give only the condensation products. The behaviour of aldehyde 1a towards amide/thioamide derivatives 6a‐d in polar and nonpolar medium has been studied. Thus, reaction of 1a with cyanoacetamide (6a), 4‐chlorobenzylidenesemicarbazone (6b) and 2‐amino‐4H‐ chromene‐3‐carboxamide (6c) in boiling ethanol afforded the 1,4‐adducts 7a‐c with addition of ethanol [20,21] (Scheme 2) (Table 1 and 2). On the other hand, reaction of aldehyde 1a with 6a,c in dry benzene containing 4‐toluenesulfonic acid as a catalyst afforded 3‐(N‐aroylamino‐1‐hydroxymethyl)‐6‐methyl‐chro‐ men‐4‐ones 8a,c, respectively, while its reaction with 4‐chlorobenzylidene‐thiosemicarbazone 6d under the same condition afforded 1‐(4‐chlorobenzylidene)‐4‐(2‐hydroxy‐6‐ methyl‐4‐oxo‐2H‐chromen‐3(4H)‐ylidene)methyl) thiosemi‐ carbazide (9d) (Scheme 3). Structures of 8a,c and 9d were established by 1H NMR spectra (Table 2). 1H NMR spectra of compounds 8a,c support the presence of OH group on C‐9 of chromone moiety, while for 9d support the presence of OH group on C‐2 of chromanone moiety. 3.2. Molecular orbital calculations The experimental 1H‐NMR spectra results were compared with theoretical data which were obtained from molecular mechanical calculations on the basis of the semi‐empirical AM1 methods of HyperChem 7.5 computer program. The calculated charges on H‐2 and H‐9 hydrogen atoms using AM1‐MO calculation method after geometrical optimization of the structures were compared with experimental 1H NMR δ values for compounds 3a‐9d (Table 3). The calculated charges on H‐2 and H‐9 hydrogen atoms (QH) are linearly related to the measured 1H‐NMR δ values for compounds 3a‐9d from the linear relations δ–NMR(H‐2) = 3.748 + 24.476 (QH‐2), r = 0.99 except (3a, 4c, 5b, 8c) and δ–NMR(H‐9) El‐Shaaer et al. / European Journal of Chemistry 2 (2) (2011) 158‐162 161 Table 2. IR and 1H NMR spectral data of newly prepared compounds. Compound IR, (/cm‐1 ) 1H NMR (DMSO‐d6, ) 3a 1604 (C═N), 1641 (C═O), 3378 (NH2) 6.60 (d, 1H, J7,8 = 6.7 Hz, H‐8), 6.92 ‐7.28 (m, 7H, Ar‐H and H‐9), 7.76 (br s, H‐2), 12.08‐12.15 (br s, 2H, NH2) 3b 3035 (CHarom), 2945 (CHaliph), 1645 (C=Opyrone), 1616 (C=N) ‐ 3c 1619 (C═Opyrone), 1652 (C═Opyrazole) 2.44 (s, 6H, Ar‐CH3), 3.14 (s, 3H, N‐CH3), 7.29‐7.50 (m, 8H, Ar‐H and Ph‐H, H‐9), 8.06 (s, 1H, H‐5), 8.66 (s, 1H, H‐2) 3d 1601 (C═C), 1619 (C═N), 1651 (C═O), 3109 (NH) 2.46 (s, 3H, Ar‐CH3), 2.50 (s, 3H, Ar‐CH3), 7.48‐7.66 (m, 2H, H‐7 and H‐8), 7.93 (s, 1H, H‐5), 8.20 (br s, 1H, H‐9), 8.71 (br s, 1H, H‐2), 11.03 (s, 1H, SH) 3e 1641 (C═Opyrone), 1701 (C═Otriazine), 3173 (NH) 2.20 (s, 3H, Ar‐CH3), 2.47 (s, 3H, Ar‐CH3), 7.64‐7.75 (m, 2H, H‐7 and H‐8), 7.93 (s, 1H, H‐5), 8.76 (s, 1H, H‐9), 9.14 (s, 1H, H‐2), 13.66 (s, 1H, SH) 4c 1640 (C═Opyrone), 1673 (C═Opyrazole), 3114 (NH) 1.17 (t, 3H, CH3), 2.09‐2.73 (m, 13H, CH2CH2 and Ar‐CH3), 3.07‐3.19 (m, 2H, SCH2), 8.06 (ss, 1H, H‐ 2), 7.00 ‐7.80 (m, 6H, Ar‐H and Ph‐H), 7.95 (s, 1H, H‐5), 8.82, 8.98 (ss, 1H, H‐9), 9.62 (s, 1H, NH) 5b 1617 (C═C), 1652 (C═Opyrone), 3254 (NH) 1.06 (m, 3H, CH3 ethoxy), 2.22 (s, 3H, Ar‐CH3), 3.29‐3.60 (m, 2H, CH2 ethoxy), 4.51‐4.77 (m, 2H, N‐ CH2‐furan), 5.94, 5.96 (ss, 1H, H‐2), 6.37 ‐6.47 (m, 3H, furan), 6.80 ‐8.14 (m, 4H, H‐9 and Ar‐H), 9.42 (d, 1H, J9,10 = 3.4 Hz, NH) 5c 1640 (C═Opyrone), 1673 (C═Opyrazole), 3389 (NH) 1.06 (m, 3H, CH3 ethoxy), 2.50 (m, 6H, Ar‐CH3), 3.19 (s, 3H, N‐CH3), 3.86 (br s, 2H, CH2 ethoxy), 6.80 (br s, 1H, H‐2), 7.06‐7.65 (m, 7H, Ar‐H and Ph‐H), 7.95 (s, 1H, H‐5), 8.89 (d, 1H, J9,10 = 3.2 Hz, H‐9), 9.68 (d, 1H, J9,10 = 3.2 Hz, NH) 7a 1616 (C═C), 1658 (C═Opyrone), 1695 (C═Oamide), 2224 (C≡N), 3388 (NH) 1.21 (m, 3H, CH3 ethoxy), 2.42 (s, 3H, Ar‐CH3), 2.88, 2.95 (ss, 2H, CH2CN), 3.69‐3.85 (m, 2H, CH2 ethoxy), 5.15 (br s, 1H, OH enolic), 6.88‐8.00 (m, 5H, H‐2, H‐9 and Ar‐H) 7b 1618 (C═N), 1645 (C═Opyrone), 1695 (C═Oamide), 3443, 3232 (NH, NH) 1.07 (m, 3H, CH3 ethoxy), 2.45 (s, 3H, Ar‐CH3), 3.32 (m, 2H, CH2 ethoxy), 6.53 (br s, 1H, H‐2), 7.42‐8.18 (m, 9H, H‐9, CH=N and Ar‐H), 9.00 (br s, 1H, NH), 10.33 (br s, 1H, NH) 7c 1604 (C═C), 1680 (C═Opyrone), 1716 (C═Oamide), 3150 (NH═C‐), 3390 (NH) 1.10 (t, 3H, CH3 ethoxy), 2.51 (s, 3H, Ar‐CH3), 3.55 ‐3.57 (br s, 2H, CH2 ethoxy), 7.19‐8.09 (m, 10H, H‐2, H‐9 and Ar‐H), 8.52 (s, 1H, NH), 8.88 (s, 1H, NH) 8a 1606 (C═C), 1667 (C═Opyrone), 1695 (C═Oamide), 2264 (C≡N), 3333 (br s, NH, OH) 2.42 (s, 3H, Ar‐CH3), 2.88, 2.95 (ss, 2H, CH2CN), 5.96 (br s, 1H, OH), 7.11‐7.44 (m, 4H, H‐9 and Ar‐ H), 8.53 (s, 1H, H‐2), 10.39 (s, 1H, NH) 8c 1603 (C═N), 1648 (C═Opyrone), 1706 (C═Oamide), 3163 (NH=C‐), 3283 (OH), 3391 (NHamide) 2.47 (s, 3H, Ar‐CH3), 5.90 (br s, 1H, OH), 6.54 (d, 1H, J9,10 = 1.22 Hz, H‐9), 7.10 ‐8.01 (m, 7H, Ar‐H), 8.16 (d, 1H, J5,7 = 0.92 Hz, H‐5), 8.46 (s, 1H, H‐2), 8.93 (s, 1H, NH), 10.02 (br s, 1H, NH) 9d 1616 (C═N), 1645 (C═Opyrone), 3166 (br s, OH), 3388, 3227 (NH, NH) 2.43 (s, 3H, Ar‐CH3), 6.87 (br s, 1H, H‐2), 7.14 (d, 1H, J7,8 = 8.5 Hz, H‐8), 7.36‐8.27 (m, 8H, H‐9, CH=N and Ar‐H), 9.12 (br s, 1H, NH), 11.54 (br s, 1H, NH) Scheme 2 Table 3. Calculated charges on H‐2 and H‐9 hydrogen atoms by AM1‐MO method and their experimental 1H NMR δ values for compounds 3a‐9d. Compound *Q / (experimental δ values in ppm) H ‐2 H ‐9 3a 0.205 (7.76) 0.136 (m)** 3c 0.198 (8.66) 0.172 (m) 3d 0.212 (8.71) 0.160 (8.20) 3e 0.211 (9.14) 0.191 (8.76) 4c 0.126 (8.06) 0.173 (8.90) 5b 0.139 (5.95) 0.168 (m) 5c 0.130 (6.80) 0.175 (8.89) 7a 0.100 (m) 0.204 (m) 7b 0.106 (6.53) 0.203 (m) 7c 0.144 ((m) 0.228 (m) 8a 0.195 (8.53) 0.101 (m) 8c 0.161 (8.46) 0.105 (6.54) 9d 0.133 (6.87) 0.217 (m) *Q = Calculated net hydrogen charges. **m = The proton is multiplet. = 2.975 + 33.65 (QH‐9), r = 0.995 except (3e), where r is regression coefficient. The positive slopes reveal a direct proportionality of the calculated charges on H‐2 and H‐9 hydrogen atoms with measured 1H‐NMR δ values, which support the proposed structures for these compounds. The dependence of 1H NMR shifts on the charge density at H‐9 is more pronounced than that found at H‐2, as indicated from slope values. 3.3. Antifungal activities Some of the newly synthesized compounds were screened for their antifungal activities against three species of fungi, Alternaria alternate, Aspergillus niger and Aspergillus flavipes using disc diffusion method [22]. 162 El‐Shaaer et al. / European Journal of Chemistry 2 (2) (2011) 158‐161 Scheme 3 Activity of each tested compound was compared with that of Flucanazole as the standard (Table 4). Compounds 3a and 4c showed very high activities against the three species of fungi. Compound 9d showed very high activities against Aspergillus niger, while compounds 3c, 3e and 5b showed lower activities against the three species of fungi. Table 4. Antifungal activities data of some the prepared compounds. Compound Diameter of inhibition zone (mm)* Alternaria alternate Aspergillus niger Aspergillus flavipes 3a ++++ ++++ ++++ 3c + + ++ 3e + ++ + 4c ++++ ++++ ++++ 5b ++ +++ ++ 7c + + + 9d +++ ++++ ++ Flucanazole ++++ ++++ ++++ * Very high active = ++++ (inhibition zone > 30 mm), High active = +++ (inhibition zone 21‐30 mm), Moderately active = ++ (inhibition zone 11‐20 mm), Lower active = + (inhibition zone 1‐10 mm). 4. Conclusion Condensation reactions of 4‐oxo‐4H‐chromene‐3‐carb‐ aldehydes 1a,b with active primary amines 2a‐e and amides/thioamides 6a‐d gave condensation products or condensation with 1,4‐addition of the solvent medium depends on the basicity of amine derivatives and polarity of the medium. Acknowledgement We thank Dr. Hala Samir, Department of Biology and Geology, Faculty of Education, Ain Shams University for evaluation of antimicrobial activities for the prepared compounds. References [1]. Ellis, G. P. Chromenes, Chromanones, and Chromones. The Chemistry of Heterocyclic Compounds; Wiley: New York, NY, Vol. 31, 1977. [2]. Horton, D. A.; Bourne, G. T.; Smythe, M. L. Chem. Rev. 2003, 103, 893‐ 930. [3]. Langer, P. Synlett 2007, 7, 1016‐1025. [4]. Ali, T. E.; Abdel‐Aziz, S. A.; El‐Shaaer, H. M.; Hanafy, F. I.; El‐Fauomy A. Z. Phosphorus, Sulfur and Silicon and the Relat. Elem. 2008, 183, 2139‐ 2160. [5]. Ibrahim, A. M.; Ali, T. E. J. Brazilian Chem. Soc. 2010, 2, 1007‐1016. [6]. Ghosh, C. K.; Patra, A. J. Heterocycl. Chem. 2008, 45, 1529‐1547. [7]. Sosnovskikh, V. Y.; Moshkin, V. S.; Kodess, M. I. Tetrahedron 2008, 64, 7877‐7889. [8]. Sosnovskikh, V. Y.; Irgashev, R. A.; Moshkin, V. S.; Kodess, M. I. Russ. Chem. Bull., Intern. Edition 2008, 57, 2146‐2151. [9]. El‐Shaaer, H. M.; Zahradnik, P.; Lacova, M.; Matulova, M. Collect. Czech. Commun. 1994, 59, 1673‐1681. [10]. Melikyan, G. S.; Lacova, M.; Kralova, K.; El‐Shaaer, H. M.; Henselova, M.; Avetisyan, A. A. Chem. Papers 1993, 47, 388‐392. [11]. El‐Shaaer, H. M.; Perjessy, A.; Zahradnik, P.; Lacova, M.; Sustekova, Z. Monatsh. Chem. 1993,124, 539‐548. [12]. Ali, T. E. Phosphorus, Sulfur, Silicon and Relat. Elem. 2007, 182, 1717‐ 1726. [13]. Ali, T. E.; Abdel‐Aziz, S. A.; El‐Shaaer, H. M.; Hanafy, F. I.; El‐Fauomy, A. Z. Turk. J. Chem. 2008, 32, 365‐374. [14]. Lácová, M.; Gašparová, R.; Koiš, P.; Boháč, A.; El‐Shaaer, H. M. Tetrahedron 2010, 66, 1410‐1419. [15]. Nohara, A.; Umetani, T.; Sanno, Y. Tetrahedron 1974, 30(19), 3553‐ 3561. [16]. Hassan, A. Y. Phosphorus, Sulfur, Silicon and the Relat. Elem. 2009, 184, 2759‐2776. [17]. Dornow, A.; Menzel, M. P. Chem. Ber. 1964, 97, 2173‐2178. [18]. Hania, M. M.. E‐Journal of Chemistry 2009, 6(S1), S508‐S514. [19]. Schiemenz, G. P. Chem. Ber. 1962, 95, 483‐486. [20]. Stankovicova, H.; Lacova, M.; Gaplovsky, A.; Chovancova, J.; Pronayova, N. Tetrahedron 2001, 57, 3455‐3464. [21]. Lacova, M.; Stankovicova, H.; Odlerova, Z. Farmaco 1995, 50(12), 885‐ 888. [22]. Rahman, A. U.; Choudhary, M. I.; Thomsen, W. J. Bioassay Techniques for Drug Development, Harwood Academic Publishers: The Netherlands 2001.