untitled European Journal of Chemistry 3 (1) (2012) 81‐86 European Journal of Chemistry ISSN 2153‐2249 (Print) / ISSN 2153‐2257 (Online)  2012 EURJCHEM DOI:10.5155/eurjchem.3.1.81‐86.507 European Journal of Chemistry Journal homepage: www.eurjchem.com Reactivity of β‐enamino ester of benzo[f]chromene: One pot synthesis of isolated and heterocycle‐fused derivatives of benzo[f] chromene Eman Abd El‐Rady* and Islam Helmy El‐Azab South Valley University, Faculty of Science, Chemistry Department, Aswan 81528, Egypt *Corresponding author at: South Valley University, Faculty of Science, Chemistry Department, Aswan 81528, Egypt. Tel.: +2.097480446; fax: +2.097480450. E‐mail address: emanelradi@hotmail.com (E.A. El‐Rady). ARTICLE INFORMATION ABSTRACT Received: 22 August 2011 Received in revised form: 27 September 2011 Accepted: 18 October 2011 Online: 31 March 2012 KEYWORDS The formation of isolated and fused benzo[f]chromene derivatives was achieved via reacting ethyl 3‐amino‐1‐phenyl‐1H‐benzo[f]chromene‐2‐carboxylate (1) with some selected reagents under basic conditions. The new compound, ethyl 3‐(dimethylaminomethyleneamino)‐1‐ phenyl‐1H‐benzo[f]chromene‐2‐carboxylate (2) was prepared from compound 1 and N,N‐ dimethyl formamide in presence of phosphorus oxychloride under mild conditions in excellent yield using Vilsmeier reaction. Also, 10‐amino‐12‐phenyl‐9‐sulfanyl‐12H‐benzo[f] chromeno[2,3‐d]pyrimidine‐11(10H)‐one (12), 10‐aryl‐14‐phenyl‐14H‐benzo[f]chromeno [2,3‐d][1,3,4]thiadiazolo[3,2‐a]pyrimidine‐13‐one (15), ethyl 3‐(4‐oxo‐2‐thioxothiazolidin‐3‐ yl)‐1‐phenyl‐1H‐benzo[f]chromene‐2‐carboxylate (18), ethyl 3‐(4‐phenyl‐2‐thioxothiazol‐ 3(2H)‐yl)‐1‐phenyl‐1H‐benzo[f]chromene‐2‐carboxylate (20), ethyl 3‐acetamido‐1‐phenyl‐ 1H‐benzo[f]chromene‐2‐carboxylate (21), and 10‐amino‐9‐methyl‐12‐phenyl‐12H‐benzo[f] chromeno[2,3‐d]pyrimidine‐11(10H)‐one (23) were prepared. The structures of these compounds were established by elemental analysis, IR, MS and NMR spectral analysis. Spectral analysis Elemental analysis Vilsmeier reaction Phosphorus oxychloride Benzo[f]chromeno[2,3‐d]pyrimidine Benzo[f]chromeno[2,3‐d][1,3,4]thiadiazolo[3,2‐ a]pyrimidine 1. Introduction Chromene and fused chromene derivatives are an important class of compounds; they are widely distributed in nature [1]. Among chromene derivatives are biologically interesting compounds showing antimicrobial activities [2‐4], inhibitors of influenza virus silidoses [5,6], compounds with antihypertensive [7] and anti‐allergic activity [8] and hair growth stimulant properties [9]. Also, chromene derivatives were found useful as antiviral [10], antiproliferation agents [11], as sex pheromone [12], with antitumor [13], central nervous system activity [14] and as anti‐HIV agent [15]. Some of their derivatives were utilized in the synthesis of macrocyclic ligands [16]. Due to these interesting properties of chromene derivatives and in continuation of our efforts directed to the synthesis of heterocyclic compounds [17‐20] we wish to report here the results of our investigation on the reactivity of ethyl 3‐amino‐1‐phenyl‐1H‐benzo[f]chromene‐2‐carboxylate (1) in the synthesize of new fused and isolated chromene compounds. 2. Experimental 2.1. Instrumentation Melting points were determined on a Gallenkamp electrothermal melting point apparatus and are uncorrected. IR spectra were recorded from potassium bromide discs using a Bruker Vector 22 FT‐IR spectrophotometer. 1H and 13C NMR spectra were obtained in deuterated dimethyl sulfoxide as solvent at 300 MHz and 75 MHz, respectively, on a Varian Gemini NMR spectrometer using TMS as internal standard. Chemical shifts are reported in δ units (ppm). Mass spectra were recorded on a Hewlett Packard MS‐5988 spectrometer at 70 eV. Elemental analysis was carried out at the Micro analytical Center of Cairo University, Egypt. 2.2. Synthesis 2.2.1. Ethyl 3‐(dimethylaminomethyleneamino)‐1‐phenyl‐ 1H‐benzo[f]chromene‐2‐carboxylate (2) A sample of compound 1 (3.44 g, 0.1 mol) was dissolved in 10 mL of DMF, the reaction mixture was stirred and cooled to 0 oC, and phosphorus oxychloride (0.1 mol, 4 mL) was added slowly. After the addition was complete, the mixture was stirred for one hour and then poured into stirred ice‐water. A saturated solution of sodium hydroxide was added slowly. A solid product was precipitated, collected by filtration, washed with water and crystallized from ethanol (Scheme 1). Colorless crystals (DMF/H2O). Yield: 73 %. M.p.: 220‐222 oC. IR (KBr, νmax, cm‐1): 1698 (CO). 1H NMR (300 MHz, CDCl3, δ, ppm): 1.75 (t, 3H, CH3), 2.47 (s, 6H, 2CH3), 4.52 (q, 2H, CH2), 7.54 (s, 1H, N=CH), 7.57‐7.95 (m, 12H, Ar‐H + CH‐pyran). MS (m/z, (%)): 400 (M+, 25). Anal. calcd. for C25H24N2O3 (400.47): C, 74.98; H, 6.04; N, 7.00. Found: C, 75.08; H, 6.33; N, 7.15%. 2.2.2. 3‐(Phenylaminomethyleneamino)‐1‐phenyl‐1H‐benzo [f]chromene‐2‐carboxylic acid (4) A mixture of 2 (1 mmol), and aniline (1 mmol) in 20 mL of ethanol containing 0.1 mL of piperidine as catalyst was refluxed for 2 hours. The compound formed during reflux was collected by filtration and re‐crystallized from dioxane/H2O to form compound 4 (Scheme 1). Colorless crystals (dioxane/H2O). Yield: 33 %. M.p.: 210‐212 oC. IR (KBr, νmax, cm‐1): 1698 (CO), 3119 (NH). 82 El‐Rady et al. / European Journal of Chemistry 3 (1) (2012) 81‐86 Scheme 1 1H NMR (300 MHz, CDCl3, δ, ppm): 7.72 (d, 1H, N=CH), 7.75 (d, H, NH), 7.76‐7.99 (m, 17H, Ar‐H + CH‐pyran), 11.50 (s, 1H, OH). 13C NMR (75 MHz, CDCl3, δ, ppm): 38.12, 99.12, 116.23, 118.12, 118.23, 120.34, 126.12, 126.14, 126.43, 128.11, 128.23, 128.32, 129.23, 129.32, 138.12, 140.32, 146.21, 151.12, 163.12, 166.23, 170.65. MS (m/z, (%)): 420 (M+, 30). Anal. calcd. for C27H20N2O3 (420.15): C, 77.13; H, 4.79; N, 6.66. Found: C, 77.43; H, 4.95; N, 6.75%. 2.2.3. 10,12‐Diphenyl‐12H‐benzo[f]chromeno[2,3‐d] pyrimidine‐11(10H)‐one (5) A mixture of 2 (1 mmol), and aniline (1 mmol) in 20 mL of pyridine was refluxed for 5 hours. The reaction mixture was concentrated under reduced pressure and the residue triturated with methanol, poured into acidified ice/water and the precipitate formed washed with water thoroughly, dried and crystallized from methanol as buff powder (Scheme 1). Yield: 40 %. M.p.: 180‐182 oC. IR (KBr, νmax, cm‐1): 1698 (CO). 1H NMR (300 MHz, CDCl3, δ, ppm): 7.45 (s, 1H, CH‐pyrimidine), 7.75‐7.97 (m, 17H, Ar‐H + CH‐pyran). MS (m/z, (%)): 402 (M+, 15). Anal. calcd. for C27H18N2O2 (402.44): C, 80.58; H, 4.51; N, 6.96. Found: C, 80.64; H, 4.69; N, 7.02%. 2.3. General procedure for synthesis of compounds (7a,b) A mixture of 2 (1 mmol), and hydrazine hydrate (excess) in 20 mL of dioxane containing 0.1 mL of triethylamine as catalyst was refluxed for 3 hours. The compound formed during reflux was collected by filtration and re‐crystallized from DMF/H2O to form compound 7a. Analogously, compound 2 reacted with phenyl hydrazine to afford compound 7b (Scheme 1). 10‐Amino‐12‐phenyl‐12H‐benzo[f]chromeno[2,3‐d]pyrimi dine‐11(10H)‐one (7a): Colorless crystals (DMF/H2O). Yield: 68 %. M.p.: 280‐282 oC. IR (KBr, νmax, cm‐1): 1699 (CO), 3410‐3415 (NH2). 1H NMR (300 MHz, CDCl3, δ, ppm): 4.69 (s, 2H, NH2), 7.49 (s, 1H, CH‐pyrimidine), 7.76‐7.98 (m, 12H, Ar‐H + CH‐pyran). 13C NMR (75 MHz, CDCl3, δ, ppm): 39.12, 102.12, 118.12, 120.34, 122.12, 123.14, 126.43, 126.71, 128.23, 128.32, 129.23, 129.32, 133.42, 140.22, 143.21, 151.12, 153.12, 166.23. MS (m/z, (%)): 341 (M+, 30). Anal. calcd. for C21H15N3O2 (341.36): C, 73.89; H, 4.43; N, 12.31. Found: C, 73.96; H, 4.59; N, 12.48%. 10‐(Phenylamino)‐12‐phenyl‐12H‐benzo[f]chromeno[2,3‐ d]pyrimidine‐11(10H)‐one (7b): Colorless crystals (DMF/H2O). Yield: 55 %. M.p.: 230‐232 oC. IR (KBr, νmax, cm‐1): 1699 (CO), 3120 (NH). 1H NMR (300 MHz, CDCl3, δ, ppm): 7.50 (s, 1H, CH‐ pyrimidine), 7.79‐8.12 (m, 17H, Ar‐H + CH‐pyran), 10.59 (s, H, NH). MS (m/z, (%)): 417 (M+, 20). Anal. calcd. for C27H19N3O2 (417.46): C, 77.68; H, 4.59; N, 10.07. Found: C, 77.73; H, 4.65; N, 10.15%. 2.3.1. Ethyl 3‐(methylsulfanylthiocarbonylamino)‐1‐phenyl‐ 1H‐benzo[f]chromene‐2‐carboxylate (10) To a vigorously stirred solution of 1 (3.44 g, 0.02 mol) in dimethyl sulfoxide (10 mL) at room temperature, carbon disulfide (1.98 g, 0.02 mol) and aqueous sodium hydroxide (1.2 mL, 20 M solution) were added simultaneously over 30 min, then the mixture was allowed to stir for additional 30 min. Dimethyl sulfate (2.5 g, 0.02 mol) was added drop wise to the reaction mixture with stirring at 5‐10 oC. After further stirring for 2 hours the mixture was poured into ice‐water. The solid so obtained was filtered off, dried and crystallized from ethanol/water (Scheme 2). White powder (EtOH/H2O). Yield: 70 %. M.p.: 110‐112 oC. IR (KBr, νmax, cm‐1): 1320 (C=S), 1699 (CO), 3120 (NH). 1H NMR (300 MHz, CDCl3, δ, ppm): 1.44 (t, 3H, CH3), 4.14 (q, 2H, CH2), 4.74 (s, 3H, SCH3), 7.78‐8.11 (m, 13H, Ar‐H + CH‐pyran + NH). MS (m/z, (%)): 451 (M+, 15). Anal. calcd. for C25H25NO3S2 (451.6): C, 66.49; H, 5.58; N, 3.10. Found: C, 66.57; H, 5.64; N, 3.23%. 2.3.2. Ethyl 1‐phenyl‐1H‐3‐(hydrazinothiocarbonylamino) benzo[f]chromene‐2‐carboxylate (11) A mixture of 10 (1 mmol), and hydrazine hydrate (excess) in 20 mL of ethanol containing 0.1 mL of piperidine as catalyst was stirred at room temperature for 5 minutes. The compound formed was collected by filtration and crystallized from mixture of ethanol and water (3:1) to form compound 11 (Scheme 2). White powder (EtOH/H2O). Yield: 70 %. M.p.: 240‐ 242 oC. IR (KBr, νmax, cm‐1): 1200 (C=S), 1700 (CO), 3130 (NH), 3420 (NH2). El‐Rady et al. / European Journal of Chemistry 3 (1) (2012) 81‐86 83 O NH2 CO2Et Ph O H N CO2Et Ph S SNa O H N CO2Et Ph S SCH3 O H N CO2Et Ph S NH-NH2 O Ph N NO NH2 SH CS2 / NaOH DMS r.tReflux 8 10 1112 N2H4.H2O 1 O Ph 9 DMSO NH S SO -CH3SH-CH3SH, -EtOH Reflux,TEA -EtOH Scheme 2 1H NMR (300 MHz, CDCl3, δ, ppm): 1.47 (t, 3H, CH3), 2.56 (s, 2H, NH2), 4.35 (q, 2H, CH2), 7.78‐8.17 (m, 14H, Ar‐H + CH‐pyran + 2NH). MS (m/z, (%)): 420 ([M+1]+, 16). Anal. calcd. for C23H21N3O3S (419.5): C, 65.85; H, 5.05; N, 10.02. Found: C, 65.99; H, 5.25; N, 10.24%. 2.3.3. 10‐Amino‐12‐phenyl‐9‐sulfanyl‐12H‐benzo[f] chromeno[2,3‐d] pyrimidine‐11(10H)‐one (12) A mixture of 10 (1 mmol) and hydrazine hydrate (excess) in 20 mL of ethanol containing 0.1 mL of piperidine as catalyst was refluxed for 8 hours. The reaction mixture was concentrated under reduced pressure and the residue triturated with methanol, the compound formed was collected by filtration and crystallized from ethanol to form compound 12 (Scheme 2). Colorless crystals (EtOH). Yield: 70 %. M.p.: 155‐157 oC. IR (KBr, νmax, cm‐1): 1700 (CO), 2350 (SH), 3425 (NH2). 1H NMR (300 MHz, CDCl3, δ, ppm): 4.47 (s, 2H, NH2), 7.78‐8.17 (m, 12H, Ar‐H + CH‐pyran), 10.23 (s, 1H, SH). MS (m/z, (%)): 373 (M+, 20). Anal. calcd. for C21H15N3O2S (373.43): C, 67.54; H, 4.05; N, 11.25. Found: C, 67.67; H, 4.23; N, 11.34%. 2.3.4. General procedure for synthesis of compounds (15a,b) Compound 12 (1 mol) in 10 mL acetic acid and benzaldehyde (1.5 mol) was acidified to pH = 5 with dilute HCl, and the reaction mixture was stirred at 150 oC for 15 hours. The solution was allowed to stand overnight, then filtered and the resulting precipitate was washed with 5 % NaHCO3 and water to neutrality and then dried, the resulting product was crystallized from ethanol. Analogously, compound 12 reacted with 4‐chlorobenzaldehyde to afford compound 15b (Scheme 3). 10,14‐Diphenyl‐14H‐benzo[f]chromeno[2,3‐d][1,3,4]thia diazolo[3,2‐a] pyrimidine‐13‐one (15a): Yellow crystals (EtOH). Yield: 55 %. M.p.: 225‐227 oC. IR (KBr, νmax, cm‐1): 1700 (CO). 1H NMR (300 MHz, CDCl3, δ, ppm): 7.78‐8.17 (m, 17H, Ar‐H + CH‐ pyran). MS (m/z, (%)): 459 (M+, 15). Anal. calcd. for C28H17N3O2S (459.52): C, 73.19; H, 3.73; N, 9.14. Found: C, 73.23; H, 3.87 N, 9.35%. 10‐(4‐Chlorophenyl)‐14‐phenyl‐14H‐benzo[f]chromeno[2,3‐ d][1,3,4]thiadiazolo[3,2‐a] pyrimidine‐13‐one (15b): Yellow crystals (EtOH). Yield: 55 %. M.p.: 210‐212 oC. IR (KBr, νmax, cm‐ 1): 1700 (CO). 1H NMR (300 MHz, CDCl3, δ, ppm): 7.75‐8.19 (m, 16H, Ar‐H + CH‐pyran). MS (m/z, (%)): 493 (M+, 40). Anal. calcd. for C28H16ClN3O2S (493.96): C, 68.08; H, 3.26; N, 8.51. Found: C, 68.24; H, 3.39; N, 8.68%. 2.3.5. Ethyl 3‐(4‐oxo‐2‐thioxothiazolidin‐3‐yl)‐1‐phenyl‐1H‐ benzo[f]chromene‐2‐carboxylate (18) To a vigorously stirred solution of 1 (3.44 g, 0.02 mol) in dimethyl formamide (10 mL) at room temperature, carbon disulfide (1.98 g, 0.02 mol) and aqueous potassium hydroxide (1.2 mL, 10 mol solution) were added simultaneously over 30 min. then the mixture was allowed to stir for additional 30 min. Chloroacetic acid (0.02 mol) was added drop wise to the reaction mixture with stirring at 5‐10 oC, and the mixture was further stirred for 2 hours and poured into ice‐water. The solid so obtained was filtered off, dried and crystallized from dioxane/H2O (Scheme 4). Yellow crystals (dioxane/H2O). Yield: 55 %. M.p.: >300 oC. IR (KBr, νmax, cm‐1): 1320 (C=S), 1700 (CO). 84 El‐Rady et al. / European Journal of Chemistry 3 (1) (2012) 81‐86 Scheme 3 O H NPh CO2Et S SK O Ph H N CO2Et S S O OH O Ph CO2Et O NH2 CO2Et Ph O Ph CO2Et N S O SO Ph CO2Et N S S Ph CS2 / KOH 1 16 1719 1820 ClCH2CO2HBrCH2COPh -KCl-KBr -H2O-H2O S S Ph OH H N Scheme 4 1H NMR (300 MHz, CDCl3, δ, ppm): 1.54 (t, 3H, CH3), 4.56 (q, 2H, CH2), 4.32 (s, 2H, thiazolyl CH2), 7.78‐8.23 (m, 12H, Ar‐H + CH‐ pyran). MS (m/z, (%)): 461 (M+, 15). Anal. calcd. for C25H19NO4S2 (461.55): C, 65.06; H, 4.15; N, 3.03. Found: C, 65.21; H, 4.34; N, 3.23%. 2.3.6. Ethyl 3‐(4‐phenyl‐2‐thioxothiazol‐3(2H)‐yl)‐1‐phenyl‐ 1H‐benzo[f]chromene‐2‐carboxylate (20) To a vigorously stirred solution of 1 (3.44 g, 0.02 mol) in dimethyl formamide (10 mL) at room temperature, carbon disulfide (1.98 g, 0.02 mol) and aqueous potassium hydroxide (1.2 mL, 10 M solution) were added simultaneously over 30 min, then the mixture was allowed to stir for additional 30 min. Phenacyl bromide (0.02 mol) was added drop wise to the reaction mixture with stirring at 5‐10 oC. The mixture was further stirred for 2 hours and poured into ice‐water. The solid so obtained was filtered off, dried and crystallized from dioxane/H2O (Scheme 4). Greenish yellow crystals (dioxane/H2O). Yield: 50 %. M.p.: >300 oC. IR (KBr, νmax, cm‐1): 1325 (C=S), 1690 (CO). 1H NMR (300 MHz, CDCl3, δ, ppm): 1.58 (t, 3H, CH3), 4.34 (q, 2H, CH2), 7.78‐8.23 (m, 18H, Ar‐H + CH‐ pyran + CH‐thiazole). MS (m/z, (%)): 508 (M+, 40), 510 (M+2, 9). Anal. calcd. for C30H22NO3S2 (508.63): C, 70.84; H, 4.36; N, 2.75. Found: C, 70.99; H, 4.46; N, 2.91%. 2.3.7. Ethyl 3‐acetamido‐1‐phenyl‐1H‐benzo[f]chromene‐2‐ carboxylate (21) A mixture of 1 (0.004 mol), acetic anhydride (0.012 mol) and zinc dust (0.28 g) was refluxed on water bath for 4 hours with stirring and filtered hot. The resulting clear solution was cooled to room temperature and the solid so obtained was filtered off (Scheme 5). Colorless crystals (dioxane/H2O). Yield: 70 %. M.p.: 120‐122 oC. IR (KBr, νmax, cm‐1): 1695 (CO), 3120 (NH). 1H NMR (300 MHz, CDCl3, δ, ppm): 1.58 (t, 3H, CH3), 2.43 (s, 3H, COCH3), 4.39 (q, 2H, CH2), 7.78‐8.23 (m, 12H, Ar‐H + CH‐ pyran), 10.23 (s, 1H, NH). MS (m/z, (%)): 387 (M+, 30). Anal. calcd. for C24H21NO4 (387.43): C, 74.40; H, 5.46; N, 3.62. Found: C, 74.53; H, 5.59; N, 3.76%. El‐Rady et al. / European Journal of Chemistry 3 (1) (2012) 81‐86 85 O NPh CH3 OH NHO NH2 O NH2 CO2Et Ph O H N CO2Et Ph CH3 O O Ph N NO NH2 CH3 Ac2O N2H4 -H2O 1 21 22 23 Scheme 5 2.3.8. 10‐Amino‐9‐methyl‐12‐phenyl‐12H‐benzo[f] chromeno[2,3‐d]pyrimidine‐11(10H)‐one (23) To a solution of 21 (0.014 mol) in absolute ethanol (10 mL) hydrazine hydrate (80 %, 0.14 mol) was added and the reaction mixture was heated for 3 hours on a water bath. The reaction mixture was cooled to room temperature and the solid so obtained was filtered off as colorless crystals, (dioxane/H2O) (Scheme 5). Yield: 60 %. M.p.: 165‐167 oC. IR (KBr, νmax, cm‐1): 1695 (CO), 3420 (NH2). 1H NMR (300 MHz, CDCl3, δ, ppm): 1.60 (s, 3H, CH3), 2.12 (s, 2H, NH2), 7.78‐8.23 (m, 12H, Ar‐H + CH‐ pyran). MS (m/z, (%)): 355 (M+, 30). Anal. calcd. for C22H17N3O2 (355.39): C, 74.35; H, 4.82; N, 11.82%. Found: C, 74.46; H, 4.99; N, 11.93%. 3. Results and discussion Ethyl 3‐(dimethylaminomethyleneamino)‐1‐phenyl‐1H‐ benzo[f]chromene‐2‐carboxylate (2) was prepared by the reaction of ethyl 3‐amino‐1‐phenyl‐1H‐benzo[f]chromene‐2‐ carboxylate (1) with dimethyl formamide in presence of phosphorus oxychloride, (Scheme 1). The structure of this compound was characterized by IR, 1H NMR, mass spectroscopy and elemental analysis. The 1H NMR showed specifically a singlet at 2.47 ppm for the two methyl groups of the dimethylamino moiety and 7.54 ppm of the formamidine proton and the typical ester absorption pattern. Also, its IR showed disappearance of the amino absorption at 3300‐3400 cm‐1. It is plausible to expect that compound 2 would yield new tetracyclic compounds when reacted with amine derivatives. Thus, treatment of compound 2 with aromatic amine in refluxing ethanol afforded a product which had m/z at 420 which is incompatible with our expectation. So, it was assumed that the reaction proceeded via losing N‐dimethylamine to give the intermediate 3 which underwent hydrolysis rather than cyclization via losing ethanol yielding what we expected as product 5, (Scheme 1). While repeating this reaction in pyridine at reflux for five hours afforded the expected 10,12‐ diphenyl‐12H‐benzo[f]chromeno[2,3‐d]pyrimidine‐11(10H)‐ one 5. Compound 5 formed via losing of N‐dimethylamine to give the intermediate 3 which cyclized through releasing of ethanol. The mass spectroscopy of compound 5 showed m/z at 405 which is compatible with its molecular weight. On the other hand, compound 2 reacted with substituted hydrazine to yield the corresponding chromeno[2,3‐d]pyrimidine derivatives 7a,b via elimination of ethanol from the corresponding intermediate 6 which cyclized via release of ethanol. The IR spectrum of 7a showed absorption bands at 3410‐3415 (NH2) and at 1699 cm‐1 for the CO function. The 1H NMR spectrum of compound 7a showed two singlets at δ 4.69 and 7.49 ppm due to amino and pyrimidino protons, respectively. On the other hand, a solution of compound 1 in dimethyl sulfoxide was treated with carbon disulfide in presence of sodium hydroxide solution. The sodium salt of dithiocarbamic acid 8 was obtained in situ and then methylated with dimethyl sulfate to yield ethyl 3‐(methylsulfanylthiocarbonylamino)‐1‐ phenyl‐1H‐benzo[f]chromene‐2‐carboxylate (10) (Scheme 2). The structure of compound 10 was confirmed by IR, 1H NMR, and mass spectroscopy and elemental analysis. The IR spectrum of compound 10 showed the disappearance of absorption bands characterized for amino function and showed the presence of absorption bands at ν 1320 cm‐1 due to C=S and 3120 cm‐1 due to the NH function. The 1H NMR spectrum of compound 10 showed a singlet at δ 4.74 ppm due to SCH3 protons. However, compound 10 containing several reactive functions represented a good intermediate for further reactions when treated with hydrazine hydrate. So, compound 10 when reacted with hydrazine hydrate in ethanol with stirring at room temperature yielded the open chain thiosemicarbazide derivative 11 via elimination of methylsulfane, while, under reflux in ethanol for 8 hours, it yielded the expected benzo[f]chromeno[2,3‐d]pyrimidine 12 via elimination of methylsulfane and ethanol. Boiling the thiosemicarbazide 11 in ethanol in presence of triethylamine yielded the same compound 12. The IR spectrum of 11 showed the presence of absorption bands at ν 1200 cm‐1 due to C=S, 1700 cm‐1 due to C=O, 3130 cm‐1 due to NH and 3420 cm‐1 due to the NH2 function. The 1H NMR spectrum of compound 11 showed a singlet at δ 2.56 ppm due to the NH2 protons. The MS of 11 showed a peak at m/z 420 ([M+1]+, 16 %). The IR spectrum of 12 showed the presence of absorption bands at ν 1700 cm‐1 due to C=O, 2350 cm‐1 due to SH and 3425 cm‐1 due to the NH2 function. However, the 1H NMR spectrum of compound 12 showed the disappearance of absorption signals characteristic for ester protons and two singlets at δ 4.47 ppm and at 10.23 ppm due to NH2 and SH protons, respectively. The MS of 12 showed a peak at m/z 373 (M+, 20 %). Aimed at the preparation of some new derivatives of β‐ lactones and/or thiazolidinone, compound 12 was allowed to react with benzaldehyde and / or 4‐chlorobenzaldehyde to give the corresponding expected Schiff's base 13. However, the isolated compounds proved to be the new and unexpected compounds 15a,b formed via simultaneous nucleophilic attack of the sulfur atom on the hydrazone carbon with cyclization to the new thiadiazole derivatives 15a,b, as shown in Scheme 3. Furthermore compound 1, when treated with carbon disulfide and potassium hydroxide solution, yielded the soluble potassium salt of dithiocarbamic acid 16 which was further treated in situ with chloroacetic acid and phenacylbromide, respectively, to afford ethyl 3‐(4‐oxo‐2‐thioxothiazolidin‐3‐yl)‐ 1‐phenyl‐1H‐benzo[f]chromene‐2‐carboxylate (18) and ethyl 1‐phenyl‐3‐(4‐phenyl‐2‐thioxothiazol‐3(2H)‐yl)‐1H‐benzo[f] chromene‐2‐carboxylate (20) via release of water from the two corresponding intermediates 17 and 19, respectively (Scheme 4). The structures of compounds 18 and 20 were confirmed by IR, 1H NMR, mass spectroscopy and elemental analysis (see experimental section). Finally, compound 1 was acylated with acetic anhydride yielding the acetyl derivative 21 which easily reacted with hydrazine hydrate to afford the new substituted 10‐amino‐9‐ methyl‐12‐phenyl‐12H‐benzo[f]chromeno[2,3‐d]pyrimidine‐ 86 El‐Rady et al. / European Journal of Chemistry 3 (1) (2012) 81‐86 11(10H)‐one (23) via intermediate 22 which formed from 21 by displacement of ethanol rather than water as shown in Scheme 5. The IR spectrum of 23 showed the presence of absorption band at ν 1710 cm‐1 due to C=O and 3420 cm‐1 due to NH2 function. The 1H NMR spectrum of compound 23 showed two singlets at δ 1.53 and 2.57 ppm due to CH3 and NH2 protons, respectively, with disappearance of absorption pattern of ester protons confirming the proposed rationale of losing ethanol. The MS of 23 showed m/z at 355 (M+, 15 %). References [1]. Curini, M.; Cravotto, G.; Epifano, F.; Giannone, G. Curr. Med. Chem. 2006, 13, 199‐222. [2]. El Agrody, A. M.; Abd El Latif, M. S.; El Hady, N. A.; Fakery, A. 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