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Cumhurbaşkanı Erdoğan: Bölücü terör örgütü Kürt kardeşlerime artık çektiremeyecek

Cumhurbaşkanı Erdoğan: Bölücü terör örgütü Kürt kardeşlerime artık çektiremeyecek

ANKARA Cumhurbaşkanı ve AK Parti Genel Başkanı Recep Tayyip Erdoğan, AK Parti Diyarbakır 6. Olağan İl Kongresinde konuşuyor. Diyarbakırla aralarına kimsenin girmesine izin vermeyeceklerini belirten Erdoğan, “Bizim Diyarbakır’la olan muhabbetimiz öyle buzdan heykel gibi güneşi görünce eriyen türden değildir. Biz, Diyarbakır’la etle tırnak gibiyiz.” dedi. “Ülkemizde sadece Kürt olduğu için baskı…

[sporunyildizi-blog]

İranlı komutan Ankara’da… Kritik görüşme başlıyor Karargah’da Orgeneral Akar tarafından askeri törenle karşılanan Tümgeneral Bakıri’nin Ankara programı oldukça yoğun. Bakıri’nin Türkiye ziyaretinde öncelikle, “terörle mücadele, bölgesel gelişmeler, savunma alanındaki ikili ilişkiler ve sınır işbirliği” konuları ele alınacak.

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HACK ONLINE EXE CHUG PATROL: READY TO RESCUE - CHUGGINGTON BOOK VIA VPN [IPHONE]

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[omc-juniperpublishers]

Novel Route for Synthesis of Anti - Hyperglycaemic Activity of Thiazolidine 2,4- Dione Derivatives As A Mannich Bases-JuniperPublishers

                   Journal of Chemistry-JuniperPublishers

Abstract

The mannish bases of Thiozolidine 2,4 -dione derivatives has come to lime light due to their multi functional biological activities. Thiazolidine- 2,4- dione is an extensively explored hetero cyclic nucleus for designing of novel agents implicated for a wide variety of pathophysiological conditions, that is, diabetes, diabetic complications ,cancer, arthritis, inflammation, microbial infection, and melanoma. Present work, synthesise quinoline attached imidozoline derivative using (3 +2) cycloaddition via imine of quinoline and TOSMIC. These derivatives were converted to mannich bases of thiozolidine 2,4 one using knoevenagel condensation. The sulfonyl derivatives of thiozolidine 2, 4 -dione were also synthesized and characterized by using alkylation conditions.

Keywords: Imidazole derivatives; Thiozolidine 2,4 one nucleus; TOSMIC; Combi- flash Chromatography

Introduction

Thiazolidine 2,4 dione (TZD) is a vital nucleolus in heterocyclic chemistry. TZD shows multidirectional phamocodynamical activities such as Anti-hyperglycemic (glitazone drugs), anti-cancer, anti microbial, anti-arthritic. Due to multidirectional pathological actions, huge explored research work has been attempted and still efforts under progress for drug candidates. The metabolic disorder of diabetic is now a day's shows major impact on human beings throughout world. The Thiazolidine 2,4-dione (TZD) derivatives act as a drug candidates such as rosiglitagone, pioglitazone, lobigli tazone, enaglitazone, netoglitazone, ozoline, daragletazone, troglitazone etc. TZD derivatives not only confine for treatment of metabolic disorder diabetic, it o shows as an inflammatory agents, and anti- cancer and for treatment of melanoma. Due to importance of TZD, derivatives many scientists have been developed various routes for synthesis. Om silakari et al. developed different TZD derivatives and evolutes their biological activity (Figure 1). Ivanildo Mangueira, da Silva and co workers [1] developed TZD derivatives using Knoevenagel condensation (Figure 2). Boja Poojary and co workers [2] synthesized and characterization of Antimicrobial activity of novel derivatives (Figure 3). Archana Kapoor and Neha Khare [3] synthesized various mannich bases of Antibacterial and antifungal activity of 2,4-thiazolidinedione and rhodanine (Figure 4). Many routes has been developed for synthesis of 2,4thiozolidinone. The Thiazolidine 2,4 dione having many active sites. Thiazolidine 2,4,dione nucleus numbering is given as fallows (Figure 5).

Materials and Methods

All reagents and starting material were procured from commercial sources (Aldrich, Alfa Aesar). Solvents were thoroughly dried before use. THF and toluene were dried using sodium metal and benzophenone.DMF was dried using CaH. The new compounds were fully characterized using Analytical methods like IR, NMR (Bruker). The melting points were recorded using on a (WRS-1A) Digital Melting Point Apparatus without correction. Infrared spectra were taken using an AVATAR 370 FT-IR spectrometer. HNMR, CNMR spectra were recorded with a Bruker spectrometer operating at 400MHz used as a Trimethyl silane reference and values recorded in ppm. The progress of reaction  was monitored using TLC system and I2 spray and KMnO4 TLC strain. The crude compounds were purified using column chromatography (100-200 mesh silica) and Combi-flash chromatography. The hydrogenolysis process was carried out using parr shaker [4-19].

Objective of this Research

lated to develop new synthetic route for preparation of the quinoline containing thiozolidin-4- one attached 1,3, 4 oxa diazole nucleus and thiazolidin-4-one attached benz imidazole and benz thiozole and benzoxazole derivatives and thoroughly characterized. The scaffolds of 2-(8-((5-(4- substituted phenyl)-1,3,4-oxadiazol-2-yl)methoxy) quinolin-5-yl)-3-(4-(trifluoromethyl)phenyl)thiazolidin-4- one(7a-h)weresynthesized and characterized.

Experimental Methods

In this research work, we prepared below compounds and mentioned in step wise manner

a) Step-1: (Z)-N-((8-(benzyloxy)quinolin-5-yl)methylene)-4- (trifluoromethyl)aniline (2)

b) Step-2: 8-(benzyloxy)-5-(1-(4-(trifluoromethyl) phenyl)- 1H-imidazol-5-yl) quinoline (3).

c) Step-3: 5-(1-(4-(trifluoromethyl) phenyl)-1H-imidazol-5- yl) quinolin-8-ol (4).

d) Step-4: 2-((5-(1-(4-(trifluoromethyl) phenyl)-1H-imidazol- 5-yl) quinolin-8-yl) oxy) acetaldehyde (5).

e) Step-5: 5-(5-(1-(4-(trifluoromethyl)phenyl)-1H-imidazol- 5-yl)quinolin-8-oxy)methylene)thiazolidine-2,4-dione (6).

f) Step-6: 3-(Amine substituted methyl)-5-(2-((5-(1-(4- (trifluoromethyl) phenyl]-1H-imidazol-5-yl]quinolin-8-yl]oxy] ethylidene)thiazolidine-2,4-dione (7a-f).

g) Step-7: 3-(sulfonyl-derivatives)-5-(2-((5-(1-(4-(trifluoromethyl) phenyl)-1H-imidazol-5-yl) quinolin-8-yl)oxy)ethylidene)thiazolidine-2,4-dione (8a-f) (Figure 6).

Reaction mechanism for Step 2 (Figure 7)

Step 1: (Z)-N-((8-(benzyloxy) quinolin-5-yl) methylene)-4-(trifluoromethyl) aniline(2)

p class="indent">8-(benzyloxy) quinoline-5-carbaldehyde (10 g, 0.038 mol),4-(trifluoromethyl] aniline (6.5 g, 0.039 mol] in dry toluene ( 100 mL) was added freshly dried molecular sieves and refluxed for 10 h under N

2

atm. The progress of reaction was monitored by TLC. After completion of starting material, toluene was evaporated under vacuum to gave crude residue of Compound- 2 (15 g) as a solid ( white colour). The crude was carried to next step (

Figure 8

).

Step 2 : 8-(benzyloxy)-5-(1-(4-(trifluoromethyl) phenyl)-1H-imidazol-5-yl)quinoline(3)

(Z)-N-((8-(benzyloxy) quinolin-5-yl)methylene)-4-(trifluoromethyl) aniline(2) (15 g, 0.036 mol)was dissolved in Dry DMF (80 mL) and cooled to O °C. To that dried K2CO3 (15 g. 108 mol) and Toluene methyl isocyanide (7.02 g, 0.036 mol) was added and warm to room temperature and stirred for 16h. The progress of reaction was monitored by TLC. After completion, reaction mixture was poured in ice cold water (100 mL) and extracted with EtOAc ( 3 x 100 mL). The organic layer was separated and washed with brine solution, dried over anhydrous Na2SO4, filtered and evaporated under vacuum to give crude residue. The obtained crude product was purified by column chromatography (100-200 mesh silica, Eluent: 80% EtOAc-Pet Ether) isolated 8-(benzyloxy)-5-(1-(4-(trifluoromethyl) phenyl)- 1H-imidazol-5-yl)quinoline(3) (10 g, yield: 64%) as a solid (Pale yellow colour). M.p. 252-255 °C. IR (KBr, cm-1): 3030, 1440, 1520, 1005, 691, 655. HNMR (d6-DMSO, 400 mHz): 5.2 (s, 1H, -CH2), 7.1 (m, 3H), 7.3-7.5 (m, 7H), 7.6-7.7 (m, 4H), 7.85(d, 1H), 8.36(d, 1H), 8.85(d, 1H ) (Figure 9).

Step 3 : 5-(1-(4-(trifluoromethyl)phenyl)-1H-imidazol- 5-yl)quinolin-8-ol (4)

8-(benzyloxy)-5-(1-(4-(trifluoromethyl)phenyl)-1H- imidazol-5-yl)quinoline(3) (10 g, 0.022 mol ) in MeOH (100 mL) was added 5% Palladium hydroxide on carbon (1 g, cat) and hydrozinated at 70 Psi under parr shaker for 3 h at room temperature. The progress of reaction was monitored by TLC. After completion, reaction mixture was filtered on cellite bed and thoroughly washed with MeOH (2 x 75 mL). The MeOH layer were collected and evaperated under vaccum to gave 5-(1-(4-(trifluoromethyl)phenyl)-1H-imidazol-5-yl)quinolin-8- ol (4)(7g, yield : 86%) as a solid (white colour)). M.p. 280-285 °C. IR (KBr, cm-1): 3620, 3014, , 1525, 1050, 691, 620 .1HNMR ( d6-DMSO, 400 mHz) : 6.5 (brs, 1H),7.1 (m, 2H), 7.3 (d, 2H), 7.63 (m, 4H),7.8(d,1H), 8.35(d, 1H), 8.8(d, 1H) (Figure 10).

Step 4 : 2-((5-(1-(4-(trifluoromethyl)phenyl)-1H- imidazol-5-yl)quinolin-8-l)oxy)acetaldehyde (5)

5-(1-(4-(trifluoromethyl) phenyl)-1H-imidazol-5-yl) quinolin-8-ol (4) (7 g, 0.017 mol) in Dry DMF (70 mL) was added K2CO3 (9.7 g, 0.07 mol, 4 eq) and stirred at rt for 30 min. To that a solution of 2-bromo-1,1-dimethoxy ethane( 1.2 eq) in DMF (20 mL) was added drop wise at 0°C and stirred for 5h. The progress of reaction was monitored by TLC. After completion, reaction mixture was filtered on cellite bed and washed with DMF (10 mL). The Reaction mixture was poured in ice cold water (200 mL) and stirred for 20 min. The reaction mixture was acidified aq NaHSO3 solution up to PH-5 and extracted with EtOAc (2 x 200 mL). The aqueous layer was collected and basified up to PH-8 with sat aq NaHCO3 sol. The aqueous layer was extracted with EtOAc (3 x 100 mL). The organic layer were collected and dried over anhydrous Na2SO4, filtered and evaporated under vacuum to gave 2-((5-(1-(4-(trifluoromethyl)phenyl)-1H-imidazol-5- yl)quinolin-8-yl)oxy) acetaldehyde (5) (5g) as a solid( white colour). M.p. 200-205 °C. IR (KBr, cm-1): 3602, 3014, 1712, 1646, 1503, 1050, 691, 644.1HNMR (d6-DMSO, 400 mHz) : 5.2 (s, 2H), 7.1 (m, 2H), 7.3(d, 2H),7.9(d, 1H), 8.36(d, 1H), 8.82(d, 1H), 9.6(s, 1H) (Figure 11).

Step 5: 5-(2-((5-(1-(4-(trifluoromethyl)phenyl)- 1H-imidazol-5-yl)quinolin-8-yl)oxy) ethylidene) thiazolidine-2,4-dione (5)

To a mixture of 2-((5-(1-(4-(trifluoromethyl)phenyl)-1H-imidazol-5-yl)quinolin-8-yl)oxy) acetaldehyde (5) (5g, 0.012 mol), thiazolidine-2,4-dione (1.62 g, 0.013 mol) in EtOH (50 mL) was added piperdine ( 2 mL) and heated at 90 °C for 6 h. The progress of reaction was monitored by TLC. After completion, Reaction mixture was evaporated under vacuum to gave crude residue. The residue was diisolve in water(100 mL) and filtered under vaccum and dried to gave (Z]-5-(2-((5-(1-(4- (trifluoromethyl) phenyl)-1H-imidazol-5-yl)quinolin-8-yl)oxy) ethylidene) thiazolidine-2,4-dione (6) ( 5.5 g, Yield: 88% ) as a solid ( brown colour).M.p:240-243 °C. IR (KBr, cm-1): 3050, 1725, 1650, 1503, 1050, 691, 644.1HNMR ( d6-DMSO, 400 mHz) : 4.6 (dd, 1H), 4.61(dd, 1H), 6.15 (dd, 1H), 7.12 (m, 2H), 7.3 (d, 2H), 7.6-7.65 (m, 4H), 7.9(d, 1H), 8.4(d, 1H), 8.6 (brs, 1H), 8.87 (d, 1H) (Figure 12).

Step 6 : 3-( Amino substituted methyl)-5-(2-((5-(1-(4- (trifluoromethyl)phenyl)-1H-imidazol-5-yl)qumolm- 8-yl)oxy)ethylidene)thiazolidine-2,4-dione &7(a-f)

To a mixture of (Z)-5-(2-((5-(1-(4-(trifluoromethyl) phenyl]- 1H-imidazol-5-yl)quinolin-8-yl)oxy)ethylidene) thiazolidine-2,4- dione (6) ( 500 mg, ), 2o Amine (1.1 eq), Para formal dehyde (3 eq) in EtOH (50 mL) was added Sc(OTf)3 (0.1 eq) and heated for 8 h. The progress of reaction was monitored by TLC. After completion, EtOH was evaporated under vaccum to give crude product. The crude was purified by reverse-phase column chromatography (C18 silica, Eluent: 30% ACN-MeOH-H2O,0.01% TFA) isolated (Z)-3-(Amino substituted methyl)-5-(2-((5- (1-(4-(trifluoromethyl]phenyl]-1H-imidazol-5-yl)quinolin-8-yl) oxy)ethylidene) thiazolidine-2,4-dione &7(a-f). 1H NMR spectra of 7(a-f) was given below Table 1 & Figure 13.

a) 3-((4-oxopiperidin-1-yl)methyl)-5-(2-((5-(1-(4- (trifluoromethyl)phenyl)-1H-imidazol-5-yl)quinolin-8-yl) oxy)ethylidene)thiazolidine-2,4-dione (7a): M.p. 280-283 °C. IR (KBr, cm-1): 3050, 3010, 1720, 1655, 1600, 1320,770,620,. 1HNMR ( d6-DMSO, 400 mHz) : 2.4 (t, 4H), 2.8 (t, 4H), 4.65 (s, 2H,), 4. 68(dd,2H), 4.7 (dd,1H), 5.1(d, 2H), 6.8 (dd, 1H), 7.1 (m, 1H), 7.3 (d, 2H), 7.6 (m, 4H), 8.0 (d, 1H), 8.43 (d, 1H), 8.81(d, 1H). 13CNMR ( d6-DMSO, 400 mHz) : 45, 53, 65, 108, 120, 122, 124, 124.5, 131, 135, 139, 145,150,164, 173, 190.

b) 3-((4-methylpiperazin-1-yl)methyl)-5-(2-((5-(1-(4- (trifluoromethyl)phenyl)-1H-imidazol-5-yl)quinolin-8-yl) oxy)ethylidene)thiazolidine-2,4-dione (7b): M.p. 290-292 °C. IR (KBr, cm-1): 3350, 3050, 1660,1610, 1320,750, 6251HNMR ( d6-DMSO, 400 mHz) : 2.3 (s, 3H), 2.4 (d, 4H), 2.45 (d, 4H), 4.63 (s, 2H,), 4.66 (dd, 1H),4.67 (dd,1H), 6.81 (dd, 1H), 7.1 (m, 2H), 7.32 (d, 2H), 7.6 (m, 4H), 8.03 (d, 1H), 8.44 (d, 1H), 8.81(d, 1H). C-NMR ( d6-DMSO, 400 mHz) : 47, 53, 58, 65, 107, 121, 122, 124, 124.5, 127, 130, 134, 138, 145,150,163, 174.

c) tert-butyl4-((2,4-dioxo-5-(2-((5-(1-(4- (trifluoromethyl)phenyl)-1H-imidazol-5-yl)quinolin-8-yl) oxy)ethylidene)thiazolidin-3-yl)methyl)piperazine-1- carboxylate (7c): M.p. 260-2262 °C. IR (KBr, cm-1): , 3014, 1713, 1650, 1620, 1505, 1310, 1050, 698, 655, HNMR ( d6-DMSO, 400 mHz) : 1.4 (s, 9H ), 2.5 (t, 4H), 3.1(t, 4H), 2.45 (d, 4H), 4.5 (s, 2H,),4.68 (dd, 1H),4.69 (dd,1H), 6.83 (dd, 1H), 7.1 (m, 2H), 7.32 (d, 2H), 7.62 (m, 4H),7.9 (d, 1H), 8.42 (d, 1H), 8.82(d, 1H). 13C-NMR ( d6-DMSO, 400 mHz) : 31, 44, 52, 65, 78, 107, 121, 124, 127, 130, 132, 139, 145,154,162, 174.

d) 3-((4-ethylpiperazin-1-yl)methyl)-5-(2-((5-(1-(4- (trifluoromethyl)phenyl)-1H-imidazol-5-yl)quinolin-8-yl) oxy)ethylidene)thiazolidine-2,4-dione (7d): M.p. 290-292 °C. IR (KBr, cm-1): 3350, 3020, 1680,1620, 1330,750, 6251HNMR ( d6-DMSO, 400 mHz) : 1.2 (t, 3H ), 2.5 (m, 10H), 4.5 (s, 2H,), 4.67(d, 1H), 4.68(d, 1H), 6.80 (dd, 1H), 7.1 (m, 2H), 7.3(d, 2H), 7.62 (m, 4H),7.8 (d, 1H), 8.42 (d, 1H), 8.82(d, 1H). C-NMR ( d6- DMSO, 400 mHz) : 14, 50, 53,58,65, 108, 122, 124, 125, 130, 132, 145,149,165, 174.

e) 3-(morpholinomethyl)-5-(2-((5-(1-(4- (trifluoromethyl)phenyl)-1H-imidazol-5-yl)quinolin-8-yl) oxy)ethylidene)thiazolidine-2,4-dione (7e): M.p. 280-282 °C. IR (KBr, cm-1): 3016, 1720, 1650, 1503, 1300, 1050, 695, 650.1HNMR ( d6-DMSO, 400 mHz) : 2.6 (t, 4H ), 3.7 (t, 4H), 4.5 (s, 2H,), 4.68 (dd, 1H), 4.69 (dd,1H), 6.80 (dd, 1H), 7.15 (m, 2H), 7.25(d, 2H), 7.62 (m, 4H),7.9(d, 1H), 8.38 (d, 1H), 8.89(d, 1H). C-NMR (d6-DMSO, 400 mHz) : 53,65, 66,107, 123, 124, 125, 130, 132, 139, 145,149,164, 178.

f) 3 - (thi o mo rpho lino methyl) - 5 -(2-((5-(1-(4- (trifluoromethyl)phenyl)-1H-imidazol-5-yl)quinolin-8-yl) oxy)ethylidene)thiazolidine-2,4-dione (7f): M.p. 272-275 °C. IR (KBr, cm-1): 3080, 1730, 1645, 1520, 1310, 1125, 670, 660, 1HNMR ( d6-DMSO, 400 mHz) : 2.6 (t, 4H ), 2.8(t, 4H), 4.51 (s, 2H,), 4.66 (dd, 1H),4.67 (dd, 1H), 6.81 (dd, 1H), 7.15 (m, 2H), 7.25(d, 2H), 7.62 (m, 4H),7.9(d, 1H), 8.37 (d, 1H), 8.86(d, 1H). C-NMR ( d6-DMSO, 400 mHz) : 27,58,63, 106, 122,123, 124, 125, 130, 131, 135,139,145,149,164, 174.

Step 7: General procedure for -3-(sulfonyl derivative)- 5-(2-((5-(1-(4-trifluoromethyl)phenyl)-1H-imidazol- 5-yl)quinolin-8-yl)oxy)ethylidene)thiazolidine-2,4- dione (8a-f)

5-(2-((5-(1-(4-(trifluoromethyl)phenyl)-1H-imidazol-5-yl) quinolin-8-yl)oxy)ethylidene) thiazolidine-2,4-dione (500 mg,1.8mmol) in Dry DMF(5 mL) was added NaH (3 eq) at 0 °C under N2 atm and stirred for 1h. To that sulfonyl chloride (1.1 eq) was added and stirred for 5h.The pogress of reaction was monitored by TLC. The reaction mixture was poured in aq sat NaHCO3 and stirred for 15 min. The aq layer was extracted with 10% MeOH-CHCl3 (3x 25 ml) and dried over anhydrous Na2SO4, filtered and evaporated under vaccum to gave crude product. The crude product was purified by Column chromatography (100-200 mesh silica) isolated 3-(sulfonyl derivative)-5-(2-((5- (1-(4-(trifluoromethyl) phenyl)-1H-imidazol-5-yl)quinolin-8-yl) oxy) ethylidene) thiazolidine-2,4-dione (8a-f) (Figure 14 and Table 2).

i. 3-(methylsulfonyl)-5-(2-((5-(1-(4- (trifluoromethyl)phenyl)-1H-imidazol-5-yl)quinolin-8-yl) oxy)ethylidene)thiazolidine-2,4-dione(8a): M.p.280-283°C. IR (KBr, cm-1): 3040, 3025, 1730, 1645,1600, 1320,1070,770,715620,.1HNMR ( d6-DMSO, 400 mHz) : 2.8 (s, 3H), 4.67 (dd, 1H),4.68 (dd,1H), 6.8 (dd, 1H), 7.1 (m, 2H), 7.3(d, 2H), 7.6 (m, 4H),7.8 (d, 1H), 8.4 (d, 1H), 8.81(d, 1H). CNMR ( d6-DMSO, 400 mHz) : 42, 64, 106, 121, 122, 124, 124.5, 126,130, 135, 138,139, 145, 148, 164, 173.

ii. 3-(ethylsulfonyl)-5-(2-((5-(1-(4-(trifluoromethyl) phenyl)-1H-imidazol-5-yl)quinolin-8-yl)oxy)ethylidene) thiazolidine-2,4-dione(8b): M.p.:88-290 °C. IR (KBr, cm-1): 3040, 3025, 1730, 1645,1603, 1325, 1075,772,715 620,.1HNMR ( d6-DMSO, 400 mHz) : 1.3 (t, 3H), 3.45 (q, 2H), 4.65 (dd, 1H),4.67 (dd,1H), 6.8 (dd, 1H), 7.13 (m, 2H), 7.32(d, 2H), 7.65 (m, 4H), 7.8 (d, 1H), 8.41 (d, 1H), 8.82(d, 1H). 13CNMR ( d6-DMSO, 400 mHz) : 10, 52, 63, 106, 121, 122, 124, 124.5, 126,130, 135, 138,139, 145, 148, 164, 173.

iii. 3-tosyl-5-(2-((5-(1-(4-(trifluoromethyl) phenyl)-1H-imidazol-5-yl)quinolin-8-yl)oxy) ethylidene) thiazolidine-2,4-dione(8c): M.p. 300-302 °C. IR (KBr, cm-1):3050, 3030, 1735, 1640,1603, 1325, 1075,770,715 620.1HNMR ( d6-DMSO, 400 mHz) : 2.3 (s, 3H), 4.68 (dd, 1H), 4.69 (dd, 1H), 6.8 (dd, 1H), 7.13 (m, 2H), 7.32(d, 2H),7.4 (d, 2H), 7.65 (m, 4H),7.7 (d, 2H), 7.8 (d, 1H), 8.42 (d, 1H), 8.85(d, 1H). 13CNMR ( d6-DMSO, 400 mHz) : 20, 64, 107, 121, 122, 123, 124, 124.5,126,128, 130,132, 133 135, 138,139, 145, 148, 155, 165, 175.

iv. 3-((4-chlorophenyl)sulfonyl)-5-(2-((5-(1-(4- (trifluoromethyl)phenyl)-1H-imidazol-5-yl)quinolin-8- yl)oxy)ethylidene)thiazolidine-2,4-dione (8d): M.p. 290292 °C. IR (KBr, cm-1): 3070, 3020, 1720, 1620,1530,1325, 1080,770,720, 655.1HNMR ( d6-DMSO, 400 mHz) : 4.68(dd, H), 4.69 (dd, 1H), 6.85 (dd, 1H), 7.15 (m, 2H), 7.28(d, 2H),7.4(d, 2H), 7.63(m, 6H),7.8(d, 2H), 7.95(d, 1H), 8.5 (d, 1H), 8.87(d, 1H). 13CNMR ( d6-DMSO, 400 mHz) : 64, 108, 121, 122, 123, 124,

124.5, 126,128, 130,132, 133 135, 139, 145, 149, 155, 162, 173.

v. 3- ((4-bromophenyl)sulfonyl)-5 - (2- ((5 - (1-(4- (trifluoromethyl)phenyl)-1H-imidazol-5-yl)quinolin-8- yl)oxy)ethylidene)thiazolidine-2,4-dione (8e): M.p. 298300 °C. IR (KBr, cm-1): 3080, 3025, 1720, 1623,1530,1325, 1085,770,725, 655.1HNMR ( d6-DMSO, 400 mHz) : 4.68(dd, 1H), 4.69 (dd,1H), 6.87 (dd, 1H), 7.18 (m, 2H), 7.28(d, 2H),7.6(m, 4H), 7.88(m, 5H), 8.4 (d, 1H), 8.8(d, 1H). 13CNMR (d6-DMSO, 400 mHz): 64.2, 107, 121, 122, 123, 124, 124.5, 126,128, 130,132, 134, 136, 139, 146, 149, 155, 163, 174.

vi. 3 - ((4-nitrophenyl)sulfonyl) - 5 - (2- ((5- (1- (4- (trifluoromethyl)phenyl)-1H-imidazol-5-yl)quinolin-8-yl) oxy)ethylidene)thiazolidine-2,4-dione(8f): M.p. 305-308 °C. IR (KBr, cm-1): 3070, 3028, 1720, 1623,1535, 1400, 1328, 1085,770,730, 655. 1HNMR ( d6-DMSO, 400 mHz) :4.68(dd, 1H),4.6 9(dd, 1H), 6.87 (dd, 1H), 7.18 (m, 2H), 7.28(d, 2H),7.6(m, 4H), 7.8(d, 1H), 8.12 (d, 2H), 8.4 (m, 3H), 8.85(d, 1H). 13CNMR ( d6-DMSO, 400 mHz) : 64.2, 107, 121, 122, 123, 124, 124.5,126,128, 130,132, 134, 136, 139, 142, 146, 149, 151155, 164,174.5.

Conclusion

In this research work we successfully synthesized and characterization, mannich bases of quinoline attached imidazoline thiozolidine 2,4-one derivatives . We are planning to these derivatives check for biological evolution. The biological evolution details will include next journal.

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ŠKODA Motorsport Chef Michal Hrabánek: Saison 2019 mit Fokus auf Kundensport und WRC 2 Pro

› ŠKODA Motorsport startet in der neu geschaffenen WRC 2 Pro-Kategorie der FIA Rallye-Weltmeisterschaft 2019 mit dem ŠKODA FABIA R5 › ŠKODA Motorsport Chef Michal Hrabánek: „Volle Konzentration auf den Kundensport, außerdem wollen wir mit Kalle Rovanperä in der WRC 2 Pro-Kategorie erfolgreich sein“ › ŠKODA verkaufte bis Ende des vergangenen Jahres 252 ŠKODA FABIA R5 an Kunden in aller Welt

Mladá Boleslav – Michal Hrabánek ist seit 2007 als Direktor von ŠKODA Motorsport bei ŠKODA AUTO tätig. Im Interview spricht er über den Start von ŠKODA Motorsport in der WRC 2 Pro-Kategorie, das Kundenprogramm in der Saison 2019 und den modernisierten ŠKODA FABIA R5.

Herr Hrabánek, der ŠKODA FABIA R5 ist zurzeit das erfolgreichste Rallye-Auto seiner Kategorie, was sind die Gründe dafür?

Michal Hrabánek: ŠKODA Motorsport verbessert kontinuierlich die Wettbewerbsfähigkeit des ŠKODA FABIA R5. Wir haben uns zuletzt vorrangig auf die Zuverlässigkeit unseres R5-Rallye-Fahrzeugs konzentriert. Als ein Ergebnis dieser Arbeit fiel in der Saison 2018 keines unserer Werksautos aufgrund eines technischen Defekts aus. Dank der Präsenz unseres Werksteams in der FIA Rallye-Weltmeisterschaft können wir die Erfahrungen sammeln, um unseren FABIA kontinuierlich weiterzuentwickeln und ihn zum besten Rallye-Auto seiner Kategorie zu machen. Die enge Zusammenarbeit zwischen der Technischen Entwicklung bei ŠKODA und den Ingenieuren und Technikern bei ŠKODA Motorsport sowie der Umstand, dass der ŠKODA FABIA R5 unter den gleichen strengen Qualitätsmaßstäben entwickelt wurde, wie sie in der Serienproduktion aller ŠKODA Automobile gelten, sind wichtige Schlüssel zum Erfolg.

Warum engagiert sich ŠKODA in der FIA- Rallye-Weltmeisterschaft 2019 mit einem Werksteam in der WRC 2 Pro-Kategorie?

Michal Hrabánek: Durch die Teilnahme unseres Werksteams an der FIA Rallye-Weltmeisterschaft sind wir näher an unseren Kunden, bekommen unmittelbares Feedback und können direkte Erfahrungen sammeln, die uns bei der Weiterentwicklung des ŠKODA FABIA R5 helfen, der dadurch das beste Rallye-Auto seiner Kategorie ist.

Was ist das Programm von ŠKODA Motorsport in der Saison 2019?

Michal Hrabánek: ŠKODA Motorsport hat seine Strategie neu ausgerichtet. Wir haben bis Ende 2018 exakt 252 Rallye-Fahrzeuge an unsere Kunden in aller Welt verkauft. Daraus resultiert eine große Verantwortung, ihnen den bestmöglichen Service zu bieten. Deshalb genießt unser Kundenprogramm in der Saison 2019 höchste Priorität. Außerdem nehmen wir mit zwei Fahrzeugen an ausgewählten Läufen zur FIA Rallye-Weltmeisterschaft teil. Kalle Rovanperä und Beifahrer Jonne Halttunen wurden in ihrem ersten Jahr in unserem Werksteam Dritte im WRC 2-Championat. Sie treten 2019 in der neuen WRC 2 Pro-Kategorie an. Wir werden außerdem unsere amtierenden WRC 2-Champions Jan Kopecký/Pavel Dresler bei ausgewählten WM-Läufen am Start sehen. Beide werden zudem in der Tschechischen Rallye-Meisterschaft starten, um dort ihren Titel zu verteidigen.

Bei der bevorstehenden Rallye Schweden haben Sie zusätzlich den amtierenden finnischen Meister Eerik Pietarinen für ŠKODA Motorsport in der WRC 2 Pro-Kategorie nominiert. Werden wir 2019 mehr Privatfahrer sehen, die für das Werksteam an den Start gehen?

Michal Hrabánek: Eerik Pietarinen wird vom finnischen ŠKODA Importeur unterstützt und hat sein Talent und seine Klasse bereits mit einem Sieg in der WRC 2-Kategorie bei der Rallye Finnland 2018 bewiesen. Wir verfolgen genau die Fortschritte talentierter ŠKODA Privatfahrer und können uns vorstellen, weitere Talente bei ausgewählten WM-Läufen in unser Werksteam zu integrieren. Das ist ein weiteres Beispiel für unsere neue Strategie, unsere Kunden noch stärker zu unterstützen.

Wie beurteilen Sie die Zukunft der WRC 2 und der neuen Pro-Kategorie?

Michal Hrabánek: Die WRC 2 ist und bleibt eine sehr attraktive Motorsportplattform, wir sehen das auch am stetig steigenden Interesse der Medien weltweit. Der Wettbewerb ist anspruchsvoll, neben ŠKODA bieten Ford, Citroen, Peugeot und Hyundai R5-Fahrzeuge an. Beim vorletzten Lauf der FIA Rallye-Weltmeisterschaft 2018 ging außerdem Volkswagen mit dem neuen Polo R5 an den Start. Außerdem kursieren Gerüchte, dass auch Toyota einen Einstieg plant. Die neue WRC 2 Pro-Kategorie für Werksteams und -fahrer startete bei der Rallye Monte Carlo. Bei der Rallye Schweden werden die Marken ŠKODA, Ford und Citroen um Meisterschaftspunkte kämpfen. Wir unterstützen alle Pläne und Ideen, die den Rallye-Sport nach vorne bringen. Die neue Serie braucht vielleicht noch etwas Zeit, um sich entwickeln zu können.

Wann können Kunden den neuen ŠKODA FABIA R5 bestellen und wann können wir die neue Fahrzeuggeneration im Wettbewerb erleben?

Michal Hrabánek: Der Zeitplan ist noch nicht festgelegt. Das Wichtigste ist für uns, dass unser Rallye-Auto zu 100 Prozent fertig entwickelt ist und sich ohne irgendwelche Kompromisse dem Wettbewerb stellen kann. Eine sorgfältige Entwicklung hat absolute Priorität. Die Homologation ist für Mitte 2019 geplant, so dass der Bestellprozess und die ersten Auslieferungen an Kunden in der zweiten Jahreshälfte starten können. Wir führen bereits eine Liste von Interessenten, die unseren neuen R5 kaufen wollen. Sollte ein Kunde Interesse an einem Fahrzeug der neuen Spezifikation R5 haben, wird er in die Liste aufgenommen. Diese Registrierung bedeutet keine Verpflichtung des Kunden, das Auto abzunehmen, sie dient nur als Reservierung. Sobald wir detailliertere Informationen wie Lieferdatum, technische Spezifikationen und so weiter haben, werden wir unsere Kunden informieren.

Zur Person: Michal Hrabánek ist seit zwölf Jahren Direktor von ŠKODA Motorsport. Zuvor hatte er verschiedene Führungspositionen in der technischen Entwicklung von ŠKODA AUTO sowie im Vertrieb und Marketing inne. Er war verantwortlich für die Entwicklung des erfolgreichen ŠKODA FABIA S2000 und dessen Nachfolger ŠKODA FABIA R5, der zurzeit das erfolgreichste Fahrzeug seiner Kategorie ist. Von 2015 bis 2018 gewann ŠKODA Motorsport unter seiner Regie vier Mal in Folge die Teamwertung in der WRC 2-Kategorie der FIA Rallye-Weltmeisterschaft.

ŠKODA AUTO › wurde in den Pioniertagen des Automobils 1895 gegründet und ist damit eines der weltweit traditionsreichsten Automobilunternehmen. › bietet seinen Kunden aktuell neun Pkw-Modellreihen an: CITIGO, FABIA, RAPID, SCALA, OCTAVIA, KAROQ, KODIAQ sowie KAMIQ und SUPERB. › lieferte 2018 weltweit mehr als 1,25 Millionen Fahrzeuge an Kunden aus. › gehört seit 1991 zum Volkswagen Konzern, einem der global erfolgreichsten Automobilhersteller. ŠKODA AUTO fertigt und entwickelt selbständig im Konzernverbund neben Fahrzeugen auch Komponenten wie Motoren und Getriebe. › unterhält drei Standorte in Tschechien; fertigt in China, Russland, der Slowakei, Algerien und Indien vornehmlich über Konzernpartnerschaften sowie in der Ukraine und Kasachstan mit lokalen Partnern. › beschäftigt mehr als 35.000 Mitarbeiter weltweit und ist in über 100 Märkten aktiv. › treibt im Rahmen der ŠKODA Strategie 2025 die Transformation vom Automobilhersteller zur „Simply Clever Company für beste Mobilitätslösungen“ voran.

Quelle. Die ŠKODA AUTO Deutschland GmbH

ŠKODA Motorsport Chef Michal Hrabánek: Saison 2019 mit Fokus auf Kundensport und WRC 2 Pro ŠKODA Motorsport Chef Michal Hrabánek: Saison 2019 mit Fokus auf Kundensport und WRC 2 Pro › ŠKODA Motorsport startet in der neu geschaffenen WRC 2 Pro-Kategorie der FIA Rallye-Weltmeisterschaft 2019 mit dem ŠKODA FABIA R5…

[netmyname-blog]

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[wisatamalam-blog]

Berburu Spot Foto Terbaik di Bandung !

Kalau mau berburu spot foto terbaik di Bandung di mana ya ? Wisata Bandung memang banyak, nah agar kamu nggak kebingungan kalau mau mendapat foto yang bagus saat wisata di Bandung, berikut ini tempat berburu spot foto terbaik saat mengunjungi tempat wisata di Bandung !

 Trizara Resorts Lembang

Trizara Resort Lembang adalah tempat wisata di Bandung yang memiliki konsep berbaur dengan alam dan mempunyai banyak spot foto bagus. Di sini kamu bisa glamping atau glamour camping, pasti seru. Trizara Resort berlokasi di Jl. Pasirwangi Wetan, Gudangkahuripan, Lembang, Gudangkahuripan, Lembang, Kabupaten Bandung Barat, Jawa Barat. Harga kamarnya mulai 1,3 jutaan.

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The Lodge Maribaya adalah tempat wisata di Bandung yang mempunyai banyak sekali spot foto yang keren banget. Viewnya yang berlatar perbukitan hijau Bandung, bikin feed Instagrammu seger banget ! The Lodge Maribaya berlokasi di Jalan Maribaya No. 149/252, RT. 03 / RW. 15, Babakan Gentong, Cibodas, Lembang, Kabupaten Bandung Barat, Jawa Barat. Harga kamarnya 300 ribuan.

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Tebing Keraton adalah tempat wisata di Bandung yang memiliki spot foto di atas batu tepi tebing, dari spot ini kamu bisa berfoto dengan latar hijaunya hutan dan vegetasi alami lainnya. Tebing Keraton berlokasi di kawasan Taman Hutan Raya Ir. H. Djuanda, Kampung Ciharegem Puncak, Desa Ciburial, Bandung, Jawa Barat. Hargat tiket masuk Tebing Keraton sebesar 10 ribu rupiah.

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Kawah Putih berada adalah tempat wisata di Bandung yang mempunyai banyak spot fotografi yang bagus banget. Kamu bisa foto-foto dengan latar belakang danau kawah yang mengeluarkan asap putih. Kawah putih berlokasi di Jl. Raya Soreang Ciwidey, Sugihmukti, Pasirjambu, Bandung, Jawa Barat. Harga tiket masuk Kawah Putih sebesar 20 ribu rupiah

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Sari Ater Camping Park adalah tempat wisata di Bandung yang menyediakan panorama alam yang keren banget ! Sari Ater Camping Park berlokasi di Jl. Raya Ciater, Ciater, Nagrak, Subang, Kabupaten Subang, Jawa Barat. Harga untuk menginap di sini sebesar 1 jutaan rupiah.

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Amazing Art World adalah tempat wisata di Bandung yang memiliki wahana lukisan-lukisan 3D yang keren. Berfoto di Amazing Art World serasa kamu sedang menjadi bagian dari lukisan 3D. Amazing Art World berlokasi di Jl. Setiabudhi No. 293, Kota Bandung. Harga tiket masuk Amazing Art World :

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Weekday : Rp. 91.000/ orang

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 *Harga tiket tersebut merupakan promo diskon 30% selama soft opening

featured image via Instagram Trizararesort

[yedi24haber]

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[ankarabaskenthaber]

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[yedi24haber]

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[yedi24haber]

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[yedi24haber]

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Cumhurbaşkanlığı Sözcüsü Kalın: PYD-PKK'nın ideolojisini kabul etmeyen binlerce Kürt var

Cumhurbaşkanlığı Sözcüsü Kalın: PYD-PKK'nın ideolojisini kabul etmeyen binlerce Kürt var

ANKARA Cumhurbaşkanlığı Sözcüsü İbrahim Kalın, CNN International’da Christiane Amanpour’un Zeytin Dalı Harekatı ve Suriye’deki duruma ilişkin sorularını yanıtladı.  Zeytin Dalı Harekatı’nın doğrudan ABD tarafından desteklenen güçleri ve bölgedeki Amerikan varlığını hedef aldığı iddiasına ilişkin Kalın, “Biz PYD/YPG’nin DEAŞ ile mücadele adı altında Amerikalılar tarafından desteklenmesi konusunu…

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'Kürt devleti projesinin gerçekleşme şansı imkansız hale geldi'

'Kürt devleti projesinin gerçekleşme şansı imkansız hale geldi'

İSTANBUL – Gülsüm İncekaya Uludağ Üniversitesi İktisadi ve İdari Bilimler Fakültesi (İİBF) Dekanı Prof. Dr. Tayyar Arı, Irak Kürt Bölgesel Yönetimi’nin yaptığı gayrimeşru referandumun ardından yaşanan gelişmelere ilişkin, “Emperyalistlerin amaçları bölgedeki Müslüman halkları birbirine düşman hale getirmek. Özellikle Kuzey Irak denemesi üzerinden yeniden tedavüle sokulan bu projenin gerçekleşme…

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'Suriye'deki Kürt ayrılıkçı gruplar yargılansın'

'Suriye'deki Kürt ayrılıkçı gruplar yargılansın'

ASTANA – SELEN TEMİZER / MUHAMMED ŞEYH YUSUF Suriyeli askeri muhalifler adına 7. Astana görüşmelerine katılan Fatih Hassun, Birleşmiş Milletler (BM) heyetine, İran destekli yabancı terörist unsurların ülkeden çıkarılmasını ve terör örgütü PKK/PYD’nin insan hakları ihlallerinden sorumlu tutulmasını içeren dosyalar sunacaklarını belirtti. Hassun, toplantının gündemine ilişkin AA muhabirine…

[yedi24haber]

'Suriye'deki Kürt ayrılıkçı gruplar yargılansın"

'Suriye'deki Kürt ayrılıkçı gruplar yargılansın"

ASTANA – SELEN TEMİZER / MUHAMMED ŞEYH YUSUF Suriyeli askeri muhalifler adına 7. Astana görüşmelerine katılan Fatih Hassun, Birleşmiş Milletler (BM) heyetine, İran destekli yabancı terörist unsurların ülkeden çıkarılmasını ve terör örgütü PKK/PYD’nin insan hakları ihlallerinden sorumlu tutulmasını içeren dosyalar sunacaklarını belirtti. Hassun, toplantının gündemine ilişkin AA muhabirine…