Обучение по природни науки и върхови технологии

2018/6, стр. 922 - 934

SYNTHESIS AND CHARACTERIZATION OF NOVEL HETEROCYCLES WITH ANTICIPATED ANTIMICROBIAL ACTIVITIES FROM PYRANOPYRAZOLE DERIVATIVE

H.M.F. Madkour
Ain Shams University
1566 Abbassia Cairo Egypt
O.E.A. Mostafa
Ain Shams University
1566 Abbassia Cairo Egypt
E.A. El-Bordany
Ain Shams University
1566 Abbassia Cairo Egypt
A.K. El-Ziaty
E-mail: ahm512@sci.asu.edu.eg
Synthetic Organic Chemistry Laboratory
Chemistry Department
Faculty of Science
Ain Shams University
1566 Abbassia Cairo Egypt
M. Nabil
Ain Shams University
1566 Abbassia Cairo Egypt

Резюме: The previously reported 6-amino-4-(4-chlorophenyl)-3-methyl-1,4dihydropyrano [2, 3-c] pyrazole-5-carbonitrile 1 was prepared and utilized as a precursor for novel heterocycles such as Benzoxazinone 4, Pyrazolopyranopyrimidines 8, 9, 12, 13 and 20 tetrazolopyrimidine 15 and triazolopyrimidine 16 with anticipated antimicrobial activity. The structural features of these novel heterocycles were characterized and confirmed by their spectral analysis as well as elemental analyses.

Ключови думи: pyrazolopyranooxazinones; pyranopyrimidines; triazolopyrimidines tetrazolopyrimidines and pyrazolopyranopyrimidinthion

Introduction

In recent years, the pyrazole fused heterocycles such as pyrano[2,3-c] pyrazole derivatives are known to possess diverse biological activities as anticancer (Han et al., 2015),antibacrerial and anti-infalmatoryactivites (Santhosh et al., 2012). The literature survey reveals that numerous condensed pyrazole derivatives have been synthesized and advanced to clinic studies with various biological activities (Duan et al., 2014). Pyrrolo[3,4-c] pyrazol-4(1H)-one derivatives have been reported to exhibitanti BVDV activity (Fargualy et al., 2013). Many substituted pyranopyrazoles are known to possess diverse biological activities as new neuropeptide S receptor antagonists (Batran et al., 2017), antitubercular and antimicrobial (Kamdar et al., 2010), antioxidant (Saundane et al., 2013). The fused pyrimidine derivatives have been constructed and evaluated their antimicrobial activity (Mahmoud et al., 2012; 2013). Bezoxazinones are one of the important ring systems that have drawn the attention for their different biological activities (Gao et al., 2017; Piecyk et al., 2017; Martinand-Lurin et al., 2014).Some pyranotriazolopyrimidine derivatives were synthesized and their antigenotoxic activity were tested in Escherichia coli PQ37 by using the SOS chromotest (Chabcloub, 2007).Based on these findings, it was of interest to synthesis newheterocyclic compounds such as Benzoxazinone 4, Pyrazolopyranopyrimidines 8, 9, 12, 13 and 20 tetrazolopyrimidine 15 and triazolopyrimidine 16 with anticipated antimicrobial activity..

Experimental

All the chemicals that we used in this paper are of high purity and have been purchased from Al-Gomhouria Company - Cairo – Egypt. All melting points were measured on a Gallenkamp electric melting point apparatus and are uncorrected. The infrared spectra were recorded in potassium bromide disks on a PyeUnicam SP-3-300 and Shimdazu FT IR 8101 PC Infrared spectrophotometers. The1HNMR was recorded on a Varian Mercury VX-300 NMR spectrometer. 1HNMR spectra were run at 300 MHz and on a Varian Gemini 200 MHz, Brucker AC-200 MHz using TMS as internal standard in deuterated chloroform (CDC13) or deuterateddimethylsulphoxide (DMSO-d6). Chemical shifts are quoted in δ and were related to that of the solvents. The mass spectra were recorded on a Shimadzu GCMS-QP1OOOEX mass spectrometer at 70 eV. Elemental analyses were carried out at the Microanalytical Center of Cairo University. All the reactions and the purity of the new compounds were followed and cheeked by TLC.

2-((4-(4-chlorophenyl)-5-cyano-3-methyl-1,4-dihydropyrano[2,3-c]pyrazol-6yl)amino)-2-oxoacetylchloride (2)

A mixture of 6-amino-4-(4-chlorophenyl)-3-methyl-1,4-dihydropyrano[2,3c] pyrazole-5-carbonitrile (1) (1.43gm, 0.005 mole) in dry toluene (50 mL) and oxalyl chloride (1 gm, 0.0075 mole) was refluxed on a hot plate for 2 hours, excess toluene and oxalyl chloride was removed under reduced pressure, the formed semisolid was washed three times with dry toluene and evaporated under reduced pressure. The semisolid remains after evaporation was allowed to react directly with the appropriate alcohol or amine in some coming reactions.

2-(2-((4-(4-chlorophenyl)-5-cyano-3-methyl-1,4-dihydropyrano[2,3-c]pyrazol6-yl)amino)-2-oxoacetamido) benzoic acid(3)

A mixture of 2-((4-(4-chlorophenyl)-5-cyano-3-methyl-1,4-dihydropyrano[2,3-c]pyrazol-6-yl)amino)-2-oxoacetyl chloride (2) (1.9 gm, 0.005 mole) and anthranilic acid (1.4 gm, 0.01 mole) was added to dry pyridine (25 mL) and refluxed for 2 hours, the solvent then removed under reduced pressure, the formed solid collected and crystallized from ethanol / acetic acid (drops), to give (3) , as yellow crystals, M.p.: 288-290ºC, yield 60%. Anal. Calcd. for C23H16N5ClO5 (477.9) C, 57.81; H,3.37; N, 14.66; Cl, 7.42. Found: C, 57.73; H, 3.44; N, 14.59; Cl, 7.33. IR (υ/cm-1): 3379, 3266 and 3119 (NH amide and NH pyrazole), 2217 (C≡N), 1681 and 1632 (C=O). MS m/z (%):478 (70.2%), 432 (50%), 353 (62.9%), 254 (52.4%), 239 (100%), 190 (53.2%) and 147 (76.6%). 1HNMR (DMSO-d 6) δ (ppm): 12.77 (s, 2H, NH amide exchangeable with D2O), 10.59 (s, 1H, NH pyrazole exchangeable with D2O), 8.71 (s, 1H, OH carboxylic exchangeable with D2O) 8.10-7.25 (m, 8H, ArH), 4.80 (s, 1H, benzylic H) and 1.87 (1s, 3H, CH3).

4-(4-chlorophenyl)-3-methyl-7-(4-oxo-4H-benzo[d][1,3]oxazin-2-yl)-1H-pyrazolo[4’,3’:5,6] pyrano[2,3-d][1,3] oxazin-5(4H)-one(4)

A mixture of 2-(2-((4-(4-chlorophenyl)-5-cyano-3-methyl1,4-dihydropyrano[2,3-c]pyrazol-6-yl)amino)-2-oxoacetamido)benzoic acid (3) and acetic anhydride (25 mL) are refluxed for 8 hours, the excess anhydride then removed under reduced pressure, the formed solid collected and crystallized from ethanol / acetic acid (drops), to give (4) , as yellow crystals, M.p.:>300ºC, yield 40%. Anal. Calcd. for C23H13N4ClO5 (460.8) C, 59.95; H,2.84; N, 12.16; Cl, 7.69. Found: C, 60.07; H, 2.77; N, 12.26; Cl, 7.60. IR (υ/cm-1): 3268 (NH pyrazole), 1765 (C=O),1628 (C=N). MS m/z (%):461 (61.2%), 322 (92.2%), 246 (100%), 177 (2.91%), 174 (13.6%) and 136 (7.8%) . 1HNMR (DMSO-d6) δ (ppm): 12.69 (s, 1H, NH pyrazole exchangeable with D2O), 8.25-7.32 (m, 8H, ArH), 5.11 (s, 1H, benzylic H) and 1.90 (s, 3H, CH3).

Methyl 2-((4-(4-chlorophenyl)-5-cyano-3-methyl-1,4-dihydropyrano[2,3-c] pyrazol-6-yl)amino) -2-oxoacetate(5) and Ethyl 2-((4-(4-chlorophenyl)-5-cyano-3-methyl-1,4-dihydropyrano [2,3-c]pyrazol-6-yl) amino)-2-oxoacetate(6)

2-((4-(4-chlorophenyl)-5-cyano-3-methyl-1,4-dihydropyrano[2,3-c]pyrazol-6 yl)amino)-2- oxoacetyl chloride (2) (1.9 gm, 0.005 mole) was added to dry methanol and/or dry ethanol (50 mL) and refluxed for 30 minutes , the solvent then removed under reduced pressure, the formed solid collected and crystallized from ethanol / acetic acid (drops), to give (5) , as yellow crystals, M.p.:>300 ºC, yield 75%. Anal. Calcd. for C 17H13N 4ClO4 (372.8) C, 54.78; H, 3.52; N, 15.03; Cl, 9.51. Found: C, 54.71; H, 3.50; N, 14.92; Cl, 9.45. IR (υ/cm 1(ν/cm-1) at: 3373 and 3207 (NH amide and NH pyrazole), 2217 (C≡N), 1723 and 1649 (C=O)MS m/z (%):M∙+ at m/e 372.8 (not observed), 357 (69.5%), 264 (74.7%), 261 (100%), 218 (63.2%) and 96 (25.3%) 1HNMR (DMSO-d6) δ (ppm): 12.21 (s, 1H, NH pyrazole exchangeable with D 2O), 10.25 (s, 1H, NH amide exchangeable with D2O), 7.43-7.17 (m, 4H, ArH), 5.01 (s, 1H, benzylic H), 1.91 and 1.84 (2s, 6H, 2CH 3 )and (6) , as yellow crystals, M.p.:>300 ºC, yield 70%. Anal. Calcd. for C 18H15N4ClO4 (386.8) C, 55.89; H,3.91; N, 14.49; Cl, 9.17. Found: C, 55.94; H, 3.82; N, 14.40; Cl, 9.24.IR (υ/cm -1): 3196 and 3121 (NH amid and NH pyrazole), 2217 (C≡N), 1725 and 1647 (C=O)MS m/z (%):386.8 (not observed), 372 (56.9% relative abundance), 312 (55.9%), 235 (100%), 189 (69.6%) and 120 (26.5%) 1HNMR (DMSO-d6) δ (ppm): 12.24 (s, 1H, NH pyrazole exchangeable with D2 O), 11.0 (s, 1H, NH amide exchangeable with D2O), 7.46-7.20 (m, 4H, ArH), 4.85 (s, 1H, benzylic H), 1.96 (q, 2H, CH2), 1.85 (s, 3H, CH 3pyrazole) and 1.30 (t, 3H, CH 3 ).

4-(4-chlorophenyl)-5-hydroxy-3-methyl-4,8-dihydropyra-zolo[4’,3’:5,6] pyrano[2,3-d] pyrimidin-7(1H)-one (8) and 4-(4-chlorophenyl)-5-hydroxy-3-methyl-4,8- dihydropyrazolo[4’,3’:5,6]pyrano[2,3-d]pyrimidine-7(1H)-thione (9)

A mixture of 6-amino-4-(4-chlorophenyl)-3-methyl-1,4-dihydropyrano[2,3c] pyrazole-5-carboxamide (7) (1.5 gm, 0.005 mole) , urea (0.3gm, 0.005 mole) and / or thiourea (0.4 gm, 0.005 mole) in dry toluene (50 mL)was refluxed on a hot plate for 24 hours. The excess solvent was removed under vacuum; the solid remained was crystallized from ethanol / acetic acid (drops) to give (8) as yellow crystals, M.p.:>300 ºC, yield 70%. Anal. Calcd. for C15H11N4ClO3 (330.7) C, 54.47; H,3.35; N, 16.94; Cl, 10.72. Found: C,54.53; H,3.42; N, 16.87; Cl, 10.79. IR (υ/cm-1): 3308, 3157 (OH & NH), 1729 (C=O), 1655 (C=N) MS m/z (%):331 (1.14%), 246 (2.83) 221 (30.6%) and 111 (1.03%). 1HNMR (DMSO-d6) δ (ppm): 12.15 (s, 1H, NH pyrazole exchangeable with D2O), 7.63-7.18 (m, 4H, ArH), 6.94 (s, 2H, 2OH exchangeable with D2O), 4.63 (s, 1H, benzylic H), 1.79 (s, 3H, CH3). and (9) as yellow crystals, M.p: 224-226 ºC, yield 70%. Anal. Calcd. C15H11N4SClO2 (346.8) C, 51.95; H,3.20; N, 16.16; Cl, 10.22; S,9.25 Found: C,51.87; H, 3.29; N, 16.10; Cl, 10. 30; S,9.17. IR (υ/cm-1): 3340 and 3166 (OH and NH), 1089 (C=S). MS m/z (%):345 (1.26% relative abundance), 268 (34.9) 236 (9.75%), 143 (5.03%). 1HNMR (DMSO-d6) δ (ppm): 11.0 (s, 1H, NH pyrazole exchangeable with D2O), 7.38-7.05 (m, 4H, ArH), 6.92 (s, 2H, SH, OH exchangeable with D2O), 5.06 (s, 1H, benzylic H) and 1.90 (s, 3H, CH3 ).

4-(4-chlorophenyl)-3-methyl-1,4-dihydropyrazolo[4’,3’:5,6]pyrano[2,3-d]pyrimidin-5-ol (10)

A mixture of 4-(4-chlorophenyl)-3-methyl-4,6-dihydropyrazolo[4’,3’:5,6] pyrano[2,3-d] pyramidin5(1H)-one (7) (1.5 gm, 0.005 mole) and formamide (20mL) was refluxed with stirring on a hot plate with magnetic stirrer at 120oC for 2 hours. The reaction mixture was poured after cooling into water and crushed ice; the solid formed was filtered off, washed with cold water and crystallized from dilute ethanol to give (10) as white crystals, M.p.: 236-238 ºC, yield 84%. The structure of 10 has been confirmed by comparison with the previously prepared from the reaction of 7 with formic acid (El-Ziaty et al., 2014).

5-chloro-4-(4-chlorophenyl)-3-methyl-1,4-dihydropyrazolo[4’,3’:5,6] pyrano[2,3-d]pyrimidine (11)

A mixture of well-dried 4-(4-chlorophenyl)-3-methyl-4,6-dihydropyrazolon [4’,3’:5,6] pyrano[2,3-d]pyrimidin-5(1H)-one (10) (1.6 gm, 0.005 mole) and phosphorous oxychloride (20 mL) was refluxed on boiling water bath for 2 hours, after completion the excess phosphorous oxychloride was almost evaporated under reduced pressure, the remained mixture was dded gradually with vigorous stirring to crushed ice, the solid formed was filtered off immediately and washed with cold water, then crystallized from ethanol to give (11) as yellow crystals, M.p: 261264 ºC, yield 40%. Anal. Calcd. C15H10N4Cl2O (333.2) C,54.07; H,3.03; N, 16.82; Cl, 21.28. Found: C,53.95; H,3.10 N, 16.89; Cl, 21.20. IR (υ/cm-1): 3303 (NH), 1650 (C=N) MS m/z (%):332 (7.9%), 293 (7.9%), 261 (8.29%), 166 (1.46%), 165 (0.77%). 1HNMR (DMSO-d6) δ (ppm): 11.0 (s, 1H, NH pyrazole exchangeable with D2O), 7.15-7.06 (m, 5H, 4ArH and pyrimidine H), 4.26 (s, 1H, benzylic H), 1.98 (s, 3H, CH3).

4-(4-chlorophenyl)-5-hydrazinyl-3-methyl-1,4-dihydropyrazolo[4’,3’:5,6] pyrano[2,3-d] pyramidne (12)

A mixture 5-chloro-4-(4-chlorophenyl)-3-methyl-1,4-dihydropyrazolo[4’,3’:5,6]pyrano [2,3-d] pyrimidine (11) (1.7gm, 0.005 mole) in ethanol (50 mL) and hydrazine hydrate (0.3 gm, 0.006 mole) was refluxed on hot plate for 4 hours. After reaction completion the excess ethanol was removed under vacuum to dryness. The solid remained was dissolved in minimum amount of ethanol, then poured into crushed ice, the solid formed was filtered off, washed with cold water and crystallized from ethanol to give (12) as white crystals, M.p.: 222-224 ºC, yield 60%. Anal. Calcd. C15H13N6ClO (328.8) C,54.80; H,3.99; N, 25.56; Cl, 10.78. Found: C,54.71; H,4.07 N, 25.48; Cl, 10.75. IR (υ/cm-1): 3411 and 3257 (NH & NH2), 1666 (NH2 bending). MS m/z (%):329 (13.6%), 206 (1.1) 188 (4.3%), 174 (2.7%) and 126 (13.1%). 1HNMR (DMSO-d6) δ (ppm): 10.2 (s, 1H, NH pyrazole exchangeable with D2O), 7.23-7.21 (m, 4H, ArH), 7.20 (m, 2H, NHNH2 exchangeable with D2O), 7.03 (s, 1H, pyrimidine -H), 6.85 (s, 1H, NHNH2 exchangeable with D2O), 4.27 (s, 1H, benzylic H), 2.11 (s, 3H, CH3).

4-(4-chlorophenyl)-5-ethoxy-3-methyl-1,4-dihydropyra zolo[4’,3’:5,6]pyrano [2,3-d] pyrimidine (13)

A mixture of 5-chloro-4-(4-chlorophenyl)-3-methyl-1,4-dihydropyrazolo[4’,3’:5,6]pyrano [2,3-d]pyrimidine (11) (1.7gm, 0.005 mole) and sodium ethoxide solution (0.5 gm sodium metal dissolved in 30 mL of dry ethanol) was refluxed for 4 hours, the mixture then cooled and neutralized with dilute acetic acid then poured to crushed ice, the formed solid is filtered off and washed with cold water, crystallized from ethanol to give (13) as white crystals, M.p: 239-241 ºC, yield 50%. Anal. Calcd. C17H 15N4ClO2 (342.8) C, 59.57; H,4.41; N, 16.34; Cl, 10.34. Found: C,59.66; H,4.50;N,16.30; Cl, 10.26. IR (υ/cm-1): 3306 (NH),1628 (C=N). MS m/z (%):343 (0.13%), 221 (100%) 222 (15.2%), 206 (0.3%), 140 (3.1%), 139 (3.0%) and 124 (1.0%). 1HNMR (DMSO-d6) δ (ppm): 11.8 (s, 1H, NH pyrazole exchangeable with D2O), 7.3-7.22 (m, 4H, ArH), 7.06 (s, 1H, pyrimidine -H), 4.39 (m, 3H, -CH2CH3 and benzylic H), 2.05 (m, 3H, -CH2CH3), 1.09 (m, 3H, CH3 pyrazole).

11-(4-chlorophenyl)-5,10-dimethyl-8,11-dihydropyrazolo[4’,3’:5,6] pyrano[3,2-e]tetrazolo[1,5-c]pyrimidine (15)

(0.68gm, 0.002 mole) of 4-(4-chlorophenyl)-5-hydrazino-3,7-dimethyl-1,4-dihydropy- razolo[4’,3’:5,6]pyrano[2,3-d] pyrimidine (14) was dissolved in 10 mL concentrated hydrochloric acid and 5 mL acetic acid at 0 oC, the mixture was stirred in ice bath and 10 mL of 5% sodium nitrite was added gradually on 30 minutes interval. After addition completion the mixture was stirred further for another 1 hour at room temperature, and then the mixture was diluted with water and crushed ice. The solid formed was filtered off, washed with cold water and crystallized from dilute ethanol to give (15) as yellow crystals, M.p.: 240-243ºC, yield 65%. Anal. Calcd. C 16H12N7ClO (353.8) C, 54.32; H,3.42; N, 27.72; Cl, 10.02. Found: C,54.40; H,3.33 N, 27.61; Cl, 10.16. IR (υ/cm-1): 3202 (NH) and 1638 (C=N). MS m/z (%):354 (4.2%), 275 (6%), 235 (15.8%), 83 (100%), 110 (14%), 245 (12.4%), 136 (19.6%), 111 (27%), 298 (9%), 256 (23.4%) and 190 (9.4%). 1HNMR (DMSO-d6) δ (ppm): 10.21 (s, 1H, NH pyrazole exchangeable with D2O), 7.43-7.38 (m, 4H, ArH), 4.61 (s, 1H, benzylic H), 2.0 (s, 6H, 2CH3) .

11-(4-chlorophenyl)-5,10-dimethyl-3-phenyl-8,11 dihydropyrazolo[4’,3’:5,6] pyrano[3,2-e][1,2,4]triazolo[4,3-c] pyrimidine (16)

A mixture of 4-(4-chlorophenyl)-5-hydrazino-3,7-dimethyl-1,4-dihydropyrazolo [4’,3’:5,6]pyrano[2,3-d] pyrimidine (14) (0.68gm, 0.002 mole) and benzoyl chloride (0.28 gm, 0.002 mole) in toluene (10 mL) was refluxed on hot plate for 24 hours. After reaction completion the excess toluene was removed under vacuum to dryness. The solid remained was dissolved in minimum amount of ethanol, then poured into water with crushed ice, the solid formed was filtered off, washed with cold water and crystallized from dilute ethanol to give (16) as yellow crystals, M.p.: 179-182ºC, yield 50%. Anal. Calcd. C23 H17N6ClO (428.9)C, 64.41; H,4.00; N, 19.60; Cl, 8.27. Found: C,64.30; H,3.95 N, 19.71; Cl, 8.35. IR (υ/cm -1): 3427 (NH) and 1220(C=N). MS m/z (%):430 (8.7%), 318 (42.9%), 113 (100%), 338 (46.8%), 324 (30.8%), 285 (33.3%), 176 (74%), 304 (13.9%), 238 (47.8%), 203 (28.4%) and 226 (39.7%). 1HNMR (DMSO-d6) δ (ppm): 11.68 (s, 1H, NH pyrazole exchangeable with D2O), 7.93-7.26 (m, 9H, ArH), 4.20 (s, 1H, benzylic H), 2.04 & 2.0 (2s, 6H, 2CH3).

1-acetyl-4-(4-chlorophenyl)-3,7-dimethyl-4,6-dihydro pyrazolo[4’,3’:5,6] pyrano[2,3-d]pyrimidin-5(1H)-one (18)

A mixture of 1-acetyl-4-(4-chlorophenyl)-3,7-dimethyl-1,4-dihydro-5H-pyrazolo[4’,3’:5,6] pyrano[2,3-d][1,3]oxazin-5-one (17) (1.85gm, 0.005 mole) in formamide (20 mL) was refluxed on a hot plate at 120 oC for 2 hours, then the reaction mixture is poured into crushed ice, the solid formed then filtered, dried and crystallized from ethanol to give (18) , as yellow crystals, M.p.:>300 ºC, yield 45%. Anal. Calcd. C 18H15N4 ClO3 (370.8) C, 58.31; H,4.08; N, 15.11; Cl, 9.56. Found: C,58.40; H,3.93 N, 15.03; Cl, 9.16. IR (υ/cm-1): 3406, 3202 (OH and NH) and 1657 (C=O) 1608 (C=N). MS m/z (%): m/e 371 (69.8%), 243 (100%), 328 (13.9%) and 264 (44.2%). 1HNMR (DMSO-d6) δ (ppm): 9.13 (s, 1H, NH pyrimidine exchangeable with D 2O), 7.30-7.18 (m, 4H, ArH), 4.98 (s, 1H, benzylic H), 2.85, 2.27 and 1.91 (3s, 9H, 3CH3) .

N-(1-acetyl-4-(4-chlorophenyl)-5-(hydrazinecarbonyl)-3-methyl-1,4-dihydropyrano[2,3-c]pyrazol-6-yl)acetamide(19)

A mixture of 1-acetyl-4-(4-chlorophenyl)-3,7-dimethyl-1,4-dihydro-5H-pyrazolo[4’,3’:5,6] pyrano[2,3-d][1,3]oxazin-5-one (17) (1.85gm, 0.005 mole) in ethanol (50 mL) and hydrazine hydrate (0.3gm, 0.006 mole) was refluxed on a hot plate for 2 hours, the solid formed on hot is filtered, dried and crystallized from ethanol / acetic acid (drops) to give (19) , as yellow crystals, M.p.:>300 ºC, yield 60%. Anal. Calcd. C18H18N5ClO4 (403.8) C, 53.54; H,4.49; N, 17.34; Cl, 8.87. Found: C,53.30; H,4.83 N, 17.21; Cl, 8.78. IR (υ/cm-1): 3425 and 3273 (NH2), 3199 (NH amide), 1663 and 1610 (C=O) MS m/z (%):404 (69% relative abundance), 264 (76.3%), 153 (100%) and 143 (72.6%) 1HNMR (DMSO-d6) δ (ppm): 9.4 and 9.13 (2s, 2H, 2NH amide exchangeable with D2O), 7.33 (s, 2H, NH2 exchangeable with D2O), 7.31-7.17 (m, 4H, ArH), 4.98 (s, 1H, benzylic H), 2.27, 1.96 and 1.91 (3s, 9H, 3CH3).

Results and discussion

In our continuous interest in the synthesis and evaluation the biological and pharmaceutical activities of heterocyclic compounds (El-Ziaty et al., 2012; 2014; 2016; 2017; Shiba et al., 2008; Abou-Elmagd et al., 2015; Mahmout et al., 2013b; El-Shahawi et al., 2016; El-Shahawi & El-Ziaty, 2017).The previously reported 6-amino-4-(4-chlorophenyl)-3-methyl-1,4-dihydro-pyrano[2,3-c] pyrazole-5-carbonitrile 1 (El-Zitay et al., 2014) was prepared and utilized as building block for novel heterocycles such as benzoxazinone derivative 4 which constructed by acetylation followed by dehydration and cyclization of the amide derivative 3. The structure feature of the benzoxazinone derivative 4 was elucidated from its elemental and spectral analysis such as its I.R spectrum showed no signal corresponding to the cyano group and showed a sharp signal at 1765 cm-1 for the lactonic carbonyl group. The mass spectrum also elucidates the structure of 4, it exhibited the molecular ion peak at 461(61%). The amide derivative 3 was prepared in situ from the reaction of the 2-oxoacetyl chloride derivative 2 with anthranilic acid in dry pyridine as a solvent. It is worth to be mentioned that, the 2-oxoacetyl chloride derivative 2 was prepared by treatment of the enaminonitrile1 with oxalyl chloride and we could not separate it. The structure of 2 was confirmed chemically by esterification with anhydrous alcohol afforded the esters 5, 6, (Scheme 1). The structure of 5,6 were confirmed from the spectral analysis. The I.R. spectrum showed signals at 1723 cm-1and 1725cm-1for the ester carbonyl group. also their 1HNMR showed the signals at 1.96 ppm (q, 2H, CH 2) and 1.30 (t, 3H, CH 3) corresponding to the ethyl group in compound 6.

Partial hydrolysis of the enaminonitile 1 by conc. Sulfuric acid afforded the well-known amid derivative 7, (Ziaty et al., 2014) which allowed reacting with urea and thiourea to give the pyrazolopyranopyrimidinone 8 and pyrazolopyranopyrimidinthion 9, respectivelly.

The amid derivative 7 was allowed to react with formamide to give the reported pyrazolopyranopyrimidine10 which structure was elucidated authentically with the previously prepared from the reaction of 1 with formic acid (El-Shahawi& El-Ziaty, 2017). Chlorination of 10 with a mixture of phosphorous oxychloride and phosphorus pentachloride afforded the chloropyrimidine derivative 11, which utilized as a precursor to the hydrazinopyrimidine12 and the ethoxypyrimidine 13 by reaction with hydrazinhydrate and/or sodethoxide respectivlly.

NNOH3CArHNH2CNAr= 4-ClC6H45 R=CH36 R=C2H51NNOH3CArHNHCNROHNNOH3CArHNHCNOOONNOH3CArHNHCNOONHHOOCOClONNOH3CArH234NOONOOSCHEME 1Ac2OClOOClHOOCNH2dry ToluenedryPyridineR

Aiming to construct novel triazolo and tetrazolopyrimidine derivatives 15 and 16, the enaminonitile derivative 1 was allowed to react with triethylorthacetate followed by hydrazinolysis to give the well-known hydrazinopyrimidine derivative 14 24 (El-Ziaty et al., 2017), [Scheme 2.] Treatment of 14 with nitrous acid afforded the tetrazolopyrimidine derivative 15 which structure was confirmed from the spectral analysis, the I.R spectrum showed no signal for the amino group also1HNMR lacks to the acidic protons of NH2.the mass spectrum also confirms the structure of 15, it exhibited the molecular ion peak at 354 (402%). Benzoylation of 14 by benzoyl chloride afforded the triazolopyrimidine derivative 16which structure was elucidated from the 1HNMR spectra which showed extra 5H arom. at 7.93-7.26 ppm. and the mass spectrum showed the molecular ion peak M+. at 430(8.9%).

Acetylation of the enaminonitle derivative 1 by acetic anhydride afforded the reported pyrazolopyranooxazinone derivative 17 (El-Ziaty et al., 2014). Reaction of the benzoxazinone derivative 17 with formamide gave the corresponding pyrazolopyranopyrimidine derivative 18. The structure feature of 18, was confirmed from the spectral analysis, the I.R. spectrum showed no signal characteristic of the lactonic carbonyl group and shoed the new signal at 1657cm-1 of the cyclic amide carbonyl group. Also the 1 HNMR spectrum showed a strong peak at 9.13ppm for the NH of the pyrimidine moiety. hydrazinolysis of 17 yielded the hydrazide derivative 19 instead of the aminopyrazolopyranopyrimidine19, Scheme 3 the structure of 20 was elucidated from the spectral and elemental analysis.

NNOH3CArHNH2CNNNOH3CArHNNHOHCCOHReflux / 2 hrs. Ar= 4-ClC6H4H2SO4conc. /0oCStirringfor1hNNOH3CArHNH2ONH2HCONH2Reflux/2hrs. NNOH3CArHNHNOHH2NXNH2Reflux/4 hrs. X8 X=O9 X=S1)T.E.O. A2) NH2-NH2NNOH3CArHNNNHNH2141017NaNO2NNOH3CArHNNNNN15NNOH3CArHNNNNPh16NNOH3CArHNNCl11POCl3NNOH3CArHNNNHNH2NNOH3CArHNNOEtNH2-NH2NaOEt1312PhCOClSCHEME 2
NNOH3CArCOCH3NOONNOH3CArCOCH3NNHONNOH3CArCOCH3NH1719COCH3ONHNH2NH2NH220AC2ONNOH3CArHNH2CN1NNOH3CArCOCH3NNONH2XAr= 4-ClC6H418SCHEME 3HCONH2

Conclusion

In conclusion, we have presented novel heterocycles with anticipated biological and pharmaceutical activates from readily available simple raw materials.

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ИМОБИЛИЗИРАНЕНАФРУКТОЗИЛТРАНСФЕРАЗА ВЪРХУКОМПОЗИТНИФИЛМИОТПОЛИМЛЕЧНА КИСЕЛИНА, КСАНТАН И ХИТОЗАН

Илия Илиев, Тонка Василева, Веселин Биволарски, Ася Виранева, Иван Бодуров, Мария Марудова, Теменужка Йовчева

ELECTRICAL IMPEDANCE SPECTROSCOPY OF GRAPHENE-E7 LIQUID-CRYSTAL NANOCOMPOSITE

Todor Vlakhov, Yordan Marinov, Georgi. Hadjichristov, Alexander Petrov

ON THE POSSIBILITY TO ANALYZE AMBIENT NOISERECORDED BYAMOBILEDEVICETHROUGH THE H/V SPECTRAL RATIO TECHNIQUE

Dragomir Gospodinov, Delko Zlatanski, Boyko Ranguelov, Alexander Kandilarov

RHEOLOGICAL PROPERTIES OF BATTER FOR GLUTEN FREE BREAD

G. Zsivanovits, D. Iserliyska, M. Momchilova, M. Marudova

ПОЛУЧАВАНЕ НА ПОЛИЕЛЕКТРОЛИТНИ КОМПЛЕКСИ ОТ ХИТОЗАН И КАЗЕИН

Антоанета Маринова, Теменужка Йовчева, Ася Виранева, Иван Бодуров, Мария Марудова

CHEMILUMINESCENT AND PHOTOMETRIC DETERMINATION OF THE ANTIOXIDANT ACTIVITY OF COCOON EXTRACTS

Y. Evtimova, V. Mihailova, L. A. Atanasova, N. G. Hristova-Avakumova, M. V. Panayotov, V. A. Hadjimitova

ИЗСЛЕДОВАТЕЛСКИ ПРАКТИКУМ

Ивелина Димитрова, Гошо Гоев, Савина Георгиева, Цвета Цанова, Любомира Иванова, Борислав Георгиев

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PARAMETRIC INTERACTION OF OPTICAL PULSES IN NONLINEAR ISOTROPIC MEDIUM

A. Dakova, V. Slavchev, D. Dakova, L. Kovachev

ДЕЙСТВИЕ НА ГАМА-ЛЪЧИТЕ ВЪРХУ ДЕЗОКСИРИБОНУКЛЕИНОВАТА КИСЕЛИНА

Мирела Вачева, Хари Стефанов, Йоана Гвоздейкова, Йорданка Енева

RADIATION PROTECTION

Natasha Ivanova, Bistra Manusheva

СРАВНИТЕЛЕН АНАЛИЗ НА СЪДЪРЖАЩИТЕ СЕ ЕСТЕСТВЕНИ РАДИОНУКЛИДИ В НЕВЕН И ЛАЙКА

Сияна Димова, Цветелина Стефанова, Йорданка Енева, Нина Архангелова

СТАБИЛНОСТ НА ЕМУЛСИИ ОТ ТИПА МАСЛО/ ВОДА С КОНЮГИРАНА ЛИНОЛОВА КИСЕЛИНА

И. Милкова-Томова, Д. Бухалова, К. Николова, И. Алексиева, И. Минчев, Г. Рунтолев

THE EFFECT OF EXTRA VIRGIN OLIVE OIL ON THE HUMAN BODY AND QUALITY CONTROL BY USING OPTICAL METHODS

Carsten Tottmann, Valentin Hedderich, Poli Radusheva, Krastena Nikolova

ИНФРАЧЕРВЕНА ТЕРМОГРАФИЯ ЗА ДИАГНОСТИКА НА ФОКАЛНА ИНФЕКЦИЯ

Рая Грозданова-Узунова, Тодор Узунов, Пепа Узунова

ЕКСПЕРИМЕНТЪТ ПО ПРИЛОЖНА ФИЗИКА И НЕГОВАТА РОЛЯ ПРИ УСВОЯВАНЕТО НА ПРАКТИКО-ПРИЛОЖНИТЕ ЗНАНИЯ ОТ КУРСАНТИТЕ И СТУДЕНТИТЕ

Николай Тодоров Долчинков, Бонка Енчева Караиванова-Долчинкова, Nikolay Dolchinkov, Bonka Karaivanova-Dolchinkova

ЕЛЕКТРИЧНИ СВОЙСТВА НА КОМПОЗИТНИ ФИЛМИ ОТ ПОЛИМЛЕЧНА КИСЕЛИНА

Ася Виранева, Иван Бодуров, Теменужка Йовчева

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PHYSICS IS AN EVER YOUNG SCIENCE

Temenuzhka Yovcheva

ТРИ ИДЕИ ЗА ЕФЕКТИВНО ОБУЧЕНИЕ

Гергана Карафезиева

МАГИЯТА НА ТВОРЧЕСТВОТО КАТО ПЪТ НА ЕСТЕСТВЕНО УЧЕНЕ В УЧЕБНИЯ ПРОЦЕС

Гергана Добрева, Жаклин Жекова, Михаела Чонос

ОБУЧЕНИЕ ПО ПРИРОДНИ НАУКИ ЧРЕЗ МИСЛОВНИ КАРТИ

Виолета Стоянова, Павлина Георгиева

ИГРА НА ДОМИНО В ЧАС ПО ФИЗИКА

Росица Кичукова, Ценка Маринова

ТЪМНАТА МАТЕРИЯ В КЛАСНАТА СТАЯ

Симона Стоянова, Анета Маринова

ПРОБЛЕМИ ПРИ ОБУЧЕНИЕТО ПО ФИЗИКА ВЪВ ВВМУ „Н. Й. ВАПЦАРОВ“

А. Христова, Г. Вангелов, И. Ташев, М. Димидов

ИЗГРАЖДАНЕ НА СИСТЕМА ОТ УЧЕБНИ ИНТЕРНЕТ РЕСУРСИ ПО ФИЗИКА И ОЦЕНКА НА ДИДАКТИЧЕСКАТА ИМ СТОЙНОСТ

Желязка Райкова, Георги Вулджев, Наталия Монева, Нели Комсалова, Айше Наби

ИНОВАЦИИ В БОРБАТА С ТУМОРНИ ОБРАЗУВАНИЯ – ЛЕЧЕНИЕ ЧРЕЗ БРАХИТЕРАПИЯ

Георги Върбанов, Радостин Михайлов, Деница Симеонова, Йорданка Енева

NATURAL RADIONUCLIDES IN DRINKING WATER

Natasha Ivanova, Bistra Manusheva

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АДАПТИРАНЕ НА ОБРАЗОВАНИЕТО ДНЕС ЗА УТРЕШНИЯ ДЕН

И. Панчева, М. Недялкова, П. Петков, Х. Александров, В. Симеонов

INTEGRATED ENGINEERING EDUCATION: THE ROLE OF ANALYSIS OF STUDENTS’ NEEDS

Veselina Kolarski, Dancho Danalev, Senia Terzieva

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ZAGREB CONNECTION INDICES OF \(\mathrm{TiO}_{2}\) NANOTUBES

Sohaib Khalid, Johan Kok, Akbar Ali, Mohsin Bashir

SYNTHESIS OF NEW 3-[(CHROMEN-3-YL) ETHYLIDENEAMINO] -PHENYL] -THIAZOLIDIN-4ONES AND THEIR ANTIBACTERIAL ACTIVITY

Ramiz Hoti, Naser Troni, Hamit Ismaili, Malesore Pllana, Musaj Pacarizi, Veprim Thaçi, Gjyle Mulliqi-Osmani

2017 година
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GEOECOLOGICAL ANALYSIS OF INDUSTRIAL CITIES: ON THE EXAMPLE OF AKTOBE AGGLOMERATION

Zharas Berdenov, Erbolat Mendibaev, Talgat Salihov, Kazhmurat Akhmedenov, Gulshat Ataeva

TECHNOGENESIS OF GEOECOLOGICAL SYSTEMS OF NORTHEN KAZAKHSTAN: PROGRESS, DEVELOPMENT AND EVOLUTION

Kulchichan Dzhanaleyeva, Gulnur Mazhitova, Altyn Zhanguzhina, Zharas Berdenov, Tursynkul Bazarbayeva, Emin Atasoy

Книжка 5
47-А НАЦИОНАЛНА КОНФЕРЕНЦИЯ НА УЧИТЕЛИТЕ ПО ХИМИЯ

В последните години тези традиционни за българското учителство конфе- ренции се организират от Българското дружество по химическо образование и история и философия на химията. То е асоцииран член на Съюза на химици- те в България, който пък е член на Европейската асоциация на химическите и

SYNTHESIS OF TiO 2-M (Cd, Co, Mn) AS A PHOTOCATALYST DEGRADATION OF METHYLENE BLUE DYE

Candra Purnawan, Sayekti Wahyuningsih, Dwita Nur Aisyah

EFFECT OF DIFFERENT CADMIUM CONCENTRATION ON SOME BIOCHEMICAL PARAMETERS IN ‘ISA BROWN’ HYBRID CHICKEN

Imer Haziri, Adem Rama, Fatgzim Latifi, Dorjana Beqiraj-Kalamishi, Ibrahim Mehmeti, Arben Haziri

PHYTOCHEMICAL AND <i>IN VITRO</i> ANTIOXIDANT STUDIES OF <i>PRIMULA VERIS</i> (L.) GROWING WILD IN KOSOVO

Ibrahim Rudhani, Florentina Raci, Hamide Ibrahimi, Arben Mehmeti, Ariana Kameri, Fatmir Faiku, Majlinda Daci, Sevdije Govori, Arben Haziri

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„СИМВОЛНИЯТ КАПИТАЛ“ НА БЪЛГАРСКОТО УЧИЛИЩЕ

Николай Цанков, Веска Гювийска

KINETICS OF PHOTO-ELECTRO-ASSISTED DEGRADATION OF REMAZOL RED 5B

Fitria Rahmawati, Tri Martini, Nina Iswati

ALLELOPATHIC AND IN VITRO ANTICANCER ACTIVITY OF STEVIA AND CHIA

Asya Dragoeva, Vanya Koleva, Zheni Stoyanova, Eli Zayova, Selime Ali

NOVEL HETEROARYLAMINO-CHROMEN-2-ONES AND THEIR ANTIBACTERIAL ACTIVITY

Ramiz Hoti, Naser Troni, Hamit Ismaili, Gjyle Mulliqi-Osmani, Veprim Thaçi

Книжка 3
OPTIMIZATION OF ENGINE OIL FORMULATION USING RESPONSE SURFACE METHODOLOGY AND GENETIC ALGORITHM: A COMPARATIVE STUDY

Behnaz Azmoon, Abolfazl Semnani, Ramin Jaberzadeh Ansari, Hamid Shakoori Langeroodi, Mahboube Shirani, Shima Ghanavati Nasab

CHEMOMETRICASSISTEDSPECTROPHOTOMETRIC ESTIMATION OF LANSOPRAZOLE AND DOMEPERIDONE IN BULK AND COMMERCIAL DOSAGE FORM

Farheen Sami, Shahnaz Majeed, Tengku Azlan Shah Tengku Mohammed, Noor Fatin Amalina Kamaruddin, Mohammad Zulhimi Atan, Syed Amir Javid Bukhari, Namra, Bushra Hasan, Mohammed Tahir Ansari

EVALUATION OF ANTIBACTERIAL ACTIVITY OF DIFFERENT SOLVENT EXTRACTS OF <i>TEUCRIUM CHAMAEDRYS</i> (L. ) GROWING WILD IN KOSOVO

Arben Haziri, Fatmir Faiku, Roze Berisha, Ibrahim Mehmeti, Sevdije Govori, Imer Haziri

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ПРИРОДОНАУЧНАТА ГРАМОТНОСТ НА УЧЕНИЦИТЕ В НАЧАЛОТО НА XXI ВЕК – В ТЪРСЕНЕ НА КОНЦЕПТУАЛНО ЕДИНСТВО

Теодора Коларова, Иса Хаджиали, Мимия Докова, Веселин Александров

COMPUTER SIMULATORS: APPLICATION FOR GRADUATES’ADAPTATION AT OIL AND GAS REFINERIES

Irena O. Dolganova, Igor M. Dolganov, Kseniya A. Vasyuchka

SYNTHESIS OF NEW [(3-NITRO-2-OXO-2H-CHROMEN4-YLAMINO) -PHENYL] -PHENYL-TRIAZOLIDIN-4-ONES AND THEIR ANTIBACTERIAL ACTIVITY

Ramiz Hoti, Hamit Ismaili, Idriz Vehapi, Naser Troni, Gjyle Mulliqi-Osmani, Veprim Thaçi

STABILITY OF RJ-5 FUEL

Lemi Türker, Serhat Variş

A STUDY OF BEGLIKTASH MEGALITHIC COMPLEX

Diana Kjurkchieva, Evgeni Stoykov, Sabin Ivanov, Borislav Borisov, Hristo Hristov, Pencho Kyurkchiev, Dimitar Vladev, Irina Ivanova

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2016 година
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THE EFFECT OF KOH AND KCL ADDITION TO THE DESTILATION OF ETHANOL-WATER MIXTURE

Khoirina Dwi Nugrahaningtyas, Fitria Rahmawati, Avrina Kumalasari

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VOLTAMMERIC SENSOR FOR NITROPHENOLS BASED ON SCREEN-PRINTED ELECTRODE MODIFIED WITH REDUCED GRAPHENE OXIDE

Arsim Maloku, Liridon S. Berisha, Granit Jashari, Eduard Andoni, Tahir Arbneshi

Книжка 3
ИЗСЛЕДВАНЕ НА ПРОФЕСИОНАЛНО-ПЕДАГОГИЧЕСКАТА РЕФЛЕКСИЯ НА УЧИТЕЛЯ ПО БИОЛОГИЯ (ЧАСТ ВТОРА)

Надежда Райчева, Иса Хаджиали, Наташа Цанова, Виктория Нечева

EXISTING NATURE OF SCIENCE TEACHING OF A THAI IN-SERVICE BIOLOGY TEACHER

Wimol Sumranwanich, Sitthipon Art-in, Panee Maneechom, Chokchai Yuenyong

NUTRIENT COMPOSITION OF CUCURBITA MELO GROWING IN KOSOVO

Fatmir Faiku, Arben Haziri, Fatbardh Gashi, Naser Troni

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CONTEXT-BASED CHEMISTRY LAB WORK WITH THE USE OF COMPUTER-ASSISTED LEARNING SYSTEM

N. Y. Stozhko, A. V. Tchernysheva, E.M. Podshivalova, B.I. Bortnik

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ПО ПЪТЯ ON THE ROAD

Б. В. Тошев

INTERDISCIPLINARY PROJECT FOR ENHANCING STUDENTS’ INTEREST IN CHEMISTRY

Stela Georgieva, Petar Todorov, Zlatina Genova, Petia Peneva

2015 година
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COMPLEX SYSTEMS FOR DRUG TRANSPORT ACROSS CELL MEMBRANES

Nikoleta Ivanova, Yana Tsoneva, Nina Ilkova, Anela Ivanova

SURFACE FUNCTIONALIZATION OF SILICA SOL-GEL MICROPARTICLES WITH EUROPIUM COMPLEXES

Nina Danchova, Gulay Ahmed, Michael Bredol, Stoyan Gutzov

INTERFACIAL REORGANIZATION OF MOLECULAR ASSEMBLIES USED AS DRUG DELIVERY SYSTEMS

I. Panaiotov, Tz. Ivanova, K. Balashev, N. Grozev, I. Minkov, K. Mircheva

KINETICS OF THE OSMOTIC PROCESS AND THE POLARIZATION EFFECT

Boryan P. Radoev, Ivan L. Minkov, Emil D. Manev

WETTING BEHAVIOR OF A NATURAL AND A SYNTHETIC THERAPEUTIC PULMONARY SURFACTANTS

Lidia Alexandrova, Michail Nedyalkov, Dimo Platikanov

Книжка 5
TEACHER’S ACCEPTANCE OF STUDENTS WITH DISABILITY

Daniela Dimitrova-Radojchikj, Natasha Chichevska-Jovanova

APPLICATION OF LASER INDUCED BREAKDOWN SPECTROSCOPY AS NONDESDUCTRIVE AND SAFE ANALYSIS METHOD FOR COMPOSITE SOLID PROPELLANTS

Amir Hossein Farhadian, Masoud Kavosh Tehrani, Mohammad Hossein Keshavarz, Seyyed Mohamad Reza Darbany, Mehran Karimi, Amir Hossein Rezayi

THE EFFECT OF DIOCTYLPHTHALATE ON INITIAL PROPERTIES AND FIELD PERFORMANCE OF SOME SEMISYNTHETIC ENGINE OILS

Azadeh Ghasemizadeh, Abolfazl Semnani, Hamid Shakoori Langeroodi, Alireza Nezamzade Ejhieh

QUALITY ASSESSMENT OF RIVER’S WATER OF LUMBARDHI PEJA (KOSOVO)

Fatmir Faiku, Arben Haziri, Fatbardh Gashi, Naser Troni

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БЛАГОДАРЯ ВИ!

Александър Панайотов

ТЕМАТА ВЪГЛЕХИДРАТИ В ПРОГРАМИТЕ ПО ХИМИЯ И БИОЛОГИЯ

Радка Томова, Елена Бояджиева, Миглена Славова, Мариан Николов

BILINGUAL COURSE IN BIOTECHNOLOGY: INTERDISCIPLINARY MODEL1)

V. Kolarski, D. Marinkova, R. Raykova, D. Danalev, S. Terzieva

ХИМИЧНИЯТ ОПИТ – НАУКА И ЗАБАВА

Елица Чорбаджийска, Величка Димитрова, Магдалена Шекерлийска, Галина Бальова, Методийка Ангелова

ЕКОЛОГИЯТА В БЪЛГАРИЯ

Здравка Костова

Книжка 3
SYNTHESIS OF FLUORINATED HYDROXYCINNAMOYL DERIVATIVES OF ANTI-INFLUENZA DRUGS AND THEIR BIOLOGICAL ACTIVITY

Boyka Stoykova, Maya Chochkova, Galya Ivanova, Luchia Mukova, Nadya Nikolova, Lubomira Nikolaeva-Glomb, Pavel Vojtíšek, Tsenka Milkova, Martin Štícha, David Havlíček

SYNTHESIS AND ANTIVIRAL ACTIVITY OF SOME AMINO ACIDS DERIVATIVES OF INFLUENZA VIRUS DRUGS

Radoslav Chayrov, Vesela Veselinova, Vasilka Markova, Luchia Mukova, Angel Galabov, Ivanka Stankova

NEW DERIVATIVES OF OSELTAMIVIR WITH BILE ACIDS

Kiril Chuchkov, Silvia Nakova, Lucia Mukova, Angel Galabov, Ivanka Stankova

MONOHYDROXY FLAVONES. PART III: THE MULLIKEN ANALYSIS

Maria Vakarelska-Popovska, Zhivko Velkov

LEU-ARG ANALOGUES: SYNTHESIS, IR CHARACTERIZATION AND DOCKING STUDIES

Tatyana Dzimbova, Atanas Chapkanov, Tamara Pajpanova

LACTOBACILLUS PLANTARUM AC 11S AS A BIOCATALYST IN MICROBIAL ELECYTOLYSIS CELL

Elitsa Chorbadzhiyska, Yolina Hubenova, Sophia Yankova, Dragomir Yankov, Mario Mitov

STUDYING THE PROCESS OF DEPOSITION OF ANTIMONY WITH CALCIUM CARBONATE

K. B. Omarov, Z. B. Absat, S. K. Aldabergenova, A. B. Siyazova, N. J. Rakhimzhanova, Z. B. Sagindykova

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TEACHING CHEMISTRY AT TECHNICAL UNIVERSITY

Lilyana Nacheva-Skopalik, Milena Koleva

ФОРМИРАЩО ОЦЕНЯВАНЕ PEER INSTRUCTION С ПОМОЩТА НА PLICКERS ТЕХНОЛОГИЯТА

Ивелина Коцева, Мая Гайдарова, Галина Ненчева

VAPOR PRESSURES OF 1-BUTANOL OVER WIDE RANGE OF THEMPERATURES

Javid Safarov, Bahruz Ahmadov, Saleh Mirzayev, Astan Shahverdiyev, Egon Hassel

Книжка 1
РУМЕН ЛЮБОМИРОВ ДОЙЧЕВ (1938 – 1999)

Огнян Димитров, Здравка Костова

NAMING OF CHEMICAL ELEMENTS

Maria Atanassova

2014 година
Книжка 6
LUBRICATION PROPERTIES OF DIFFERENT PENTAERYTHRITOL-OLEIC ACID REACTION PRODUCTS

Abolfazl Semnani, Hamid Shakoori Langeroodi, Mahboube Shirani

ALLELOPATHIC AND CYTOTOXIC ACTIVITY OF ORIGANUM VULGARE SSP. VULGARE GROWING WILD IN BULGARIA

Asya Pencheva Dragoeva, Vanya Petrova Koleva, Zheni Dimitrova Nanova, Mariya Zhivkova Kaschieva, Irina Rumenova Yotova

Книжка 5
GENDER ISSUES OF UKRAINIAN HIGHER EDUCATION

Н.H.Petruchenia, M.I.Vorovka

МНОГОВАРИАЦИОННА СТАТИСТИЧЕСКА ОЦЕНКА НА DREEM – БЪЛГАРИЯ: ВЪЗПРИЕМАНЕ НА ОБРАЗОВАТЕЛНАТА СРЕДА ОТ СТУДЕНТИТЕ В МЕДИЦИНСКИЯ УНИВЕРСИТЕТ – СОФИЯ

Радка Томова, Павлина Гатева, Радка Хаджиолова, Зафер Сабит, Миглена Славова, Гергана Чергарова, Васил Симеонов

MUSSEL BIOADHESIVES: A TOP LESSON FROM NATURE

Saâd Moulay Université Saâd Dahlab de Blida, Algeria

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ЕЛЕКТРОННО ПОМАГАЛO „ОТ АТОМА ДО КОСМОСА“ ЗА УЧЕНИЦИ ОТ Х КЛАС

Силвия Боянова Професионална гимназия „Акад. Сергей П. Корольов“ – Дупница

ЕСЕТО КАТО ИНТЕГРАТИВЕН КОНСТРУКТ – НОРМАТИВЕН, ПРОЦЕСУАЛЕН И ОЦЕНЪЧНО-РЕЗУЛТАТИВЕН АСПЕКТ

Надежда Райчева, Иван Капурдов, Наташа Цанова, Иса Хаджиали, Снежана Томова

44<sup>-ТA</sup> МЕЖДУНАРОДНА ОЛИМПИАДА ПО ХИМИЯ

Донка Ташева, Пенка Василева

ДОЦ. Д.П.Н. АЛЕКСАНДЪР АТАНАСОВ ПАНАЙОТОВ

Наташа Цанова, Иса Хаджиали, Надежда Райчева

COMPUTER ASSISTED LEARNING SYSTEM FOR STUDYING ANALYTICAL CHEMISTRY

N. Y. Stozhko, A. V. Tchernysheva, L.I. Mironova

С РАКЕТНА ГРАНАТА КЪМ МЕСЕЦА: БОРБА С ЕДНА ЛЕДЕНА ЕПОХА В ГОДИНАТА 3000 СЛЕД ХРИСТА. 3.

С РАКЕТНА ГРАНАТА КЪМ МЕСЕЦА:, БОРБА С ЕДНА ЛЕДЕНА ЕПОХА, В ГОДИНАТА 000 СЛЕД ХРИСТА. .

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ВИСША МАТЕМАТИКА ЗА УЧИТЕЛИ, УЧЕНИЦИ И СТУДЕНТИ: ДИФЕРЕНЦИАЛНО СМЯТАНЕ

Б. В. Тошев Българско дружество за химическо образование и история и философия на химията

ВАСИЛ ХРИСТОВ БОЗАРОВ

Пенка Бозарова, Здравка Костова

ЖИВАТА ПРИРОДА

Б. В. Тошев

БИБЛИОГРАФИЯ НА СТАТИИ ЗА МИСКОНЦЕПЦИИТЕ В ОБУЧЕНИЕТО ПО ПРИРОДНИ НАУКИ ВЪВ ВСИЧКИ ОБРАЗОВАТЕЛНИ НИВА

Б. В. Тошев Българско дружество за химическо образование и история и философия на химията

Книжка 2
BOTYU ATANASSOV BOTEV

Zdravka Kostova, Margarita Topashka-Ancheva

CHRONOLOGY OF CHEMICAL ELEMENTS DISCOVERIES

Maria Atanassova, Radoslav Angelov

Книжка 1
КАК ДА МОТИВИРАМЕ УЧЕНИЦИТЕ OT VII КЛАС ДА УЧАТ

Маргарита Бозова, Петко Бозов

ОБРАЗОВАНИЕ ЗА ПРИРОДОНАУЧНА ГРАМОТНОСТ

Адриана Тафрова-Григорова

2013 година
Книжка 6
DIFFERENTIAL TEACHING IN SCHOOL SCIENCE EDUCATION: CONCEPTUAL PRINCIPLES

G. Yuzbasheva Kherson Academy of Continuing Education, Ukraine

АНАЛИЗ НА ПОСТИЖЕНИЯТА НА УЧЕНИЦИТЕ ОТ ШЕСТИ КЛАС ВЪРХУ РАЗДЕЛ „ВЕЩЕСТВА И ТЕХНИТЕ СВОЙСТВА“ ПО „ЧОВЕКЪТ И ПРИРОДАТА“

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