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ÖZET Gerilimli yedi ve altı üyeli siklik allenlerin sentezi için yeni bir sentetik yöntem geliştirildi. Bu maksatla, ailen öncüleri olan 2-bromo-3-trimetilsilil- siklohepten (150) ve 2-boromo-3-trimetilsililsiklohekzen (151) bilinen yöntemlerin uygulanmasıyla sentezlendi. SiMeq SiMeo Br SiMe3 150 151 152 150 ve 151'in florür bazlarıyla eliminasyonu 1,2-sikloheptadien (42) ve 1,2-siklohekzadien'i (43) verdi. Bu allenler DBI ile [4+2] Diels-Alder katılmasıyla yakalandılar. 1,2-Siklopentadien'in (44) sentezi için çıkış bileşiği olan 2-bromo-3-trimetilsililsiklopenten (152), florür bazları ile her hangi eliminasyon reaksiyonu vermedi. >v 43I I 1,2-siklopentadien'in (44) bir türevini sentezlemek için 1- fenilsiklopenten (190), bilinen bir yöntemle sentezlendi. 190 bileşiğinin hidroborasyonu 2-fenilsiklopentanol'u (196) verdi. 196'nın Cr03 ile yükseltgenmesiyle 2-fenilsiklopentanon (197) elde edildi. 2-fenil-1-iyodosiklopenten (155) ve 3-fenil-2-iyo- dosiklopenten (156); keton 197'nin hidrazinhidrat, iyot ve NEt3 ile muamele edilmesiyle elde edildiler. 1 55'in t-BuOK ile elimi- nasyonu beklenen 1-fenil-1,2-siklopentadien (114) yerine 1-fenil- siklopenten (190) ve 1,2-difenilsiklopeten'i (214) verdi. 156'nın t-BuOK ile eliminasyonu, 155'e izomerizasyonla sonuçlandı. 190 Ph 196 cr 197 155 156 ör 214 Ill SUMMARY A new synthetic methodology was developed for the synthesis of seven and six-membered strained cyclic allenes. For this purpose, alien precursors 2-bromo-3-trimethylsilylcyc- loheptene (150) and 2-bromo-3-trimethylsilylcyclohexene (151) were synthesized by means of the known methods. SiMe, SiMe, SiMe 150 151 152 Fluorid base-eliminations of 150 and 151 gave 1,2-cyclohep- tadiene (42) and 1,2-cyclohexadiene (43). These allenes were trapped with DBI as [4+2] Diels-Alder adduct and characterized. 2- Bromo-3-trimethylsilylcyclopentene (152), the precursor of 1,2- cyclopentadiene (44), did not give the an elimination reactions with flouride bases. >N 43 44IV In order to synthesize a derivative of 1,2-cyclopentadiene (44), 1- phenylclopentene (190) was synthesized by the known methods. Hydroboration of 190 followed by H2O2 oxidation gave 2- phenylcyclopentanole (196). The oxidation of 196 with Cr03 af forded the corresponding ketone, 2-phenylcyclopentanone (197). Ph Ph &° 190 196 197 2-Phenyl-1-iodidecyclopentene (155) and 3-phenyl-2-iodidecyclo- pentene (156) were obtained by means of treatment of ketone 197 with hydrazinehidrate, iodine and NEt3. The base elimination of 155 with t-BuOK at 240°C gave 1-phenylcyclopentene (190) and 1,2-diphenylcyclopentene (214) instead of 1-pheny]-1,2-cyclo- pentadiene (114) desired. The elimination of 156 with t-BuOK was resulted in the izomerization to 155. 155 156 214 173

In this work; the synthesis of the 1,2-Cyclopentadieneand 1, 2-CycloheXadiene was worked on. First, 5,5-Dibromobicyclo2.1.01 •4 pentane was synthesized as the startingcompound. It was seen that 1,2-cyclopentadiene has not fformed from the reaction of 5,5-dibromo-bicyclo 2.1.01 •4pentane with CH3L;- and BuLL2-Bromo-3-trimethylsilylcyclohexene was syn-thesized as astar-ting material for the synthesis of 1,2-cyclohexadiene.It has been seen that 1,2-cyclohexadiene forms from thereaction of 2-bromo-3-trimethylsilylcyclohexene wi th florUrbases. Thus, for the synthesis of cyclic allene a new methodwas improved. 70

WOS: 000408915800013, Carbonic anhydrase (CA; EC 4.2.1.1) is used for remedial purposes for several years, as there is significant focus on expanding more new activators (CAAs) and high affinity inhibitors. Alzheimers disease and other similar ailments such as dementia and vascular dementia with Lewy bodies reduce cholinergic activity in the important areas involved in cognition and memory. Prevalent drugs for the symptomatic therapy of dementia are significant in increasing the associated cholinergic deficiency by inhibiting acetylcholinesterase (AChE). These six-membered carbocycles showed nice inhibitory action against AChE and human carbonic anhydrase (hCA) II and I isoforms. The hCA I, II, and AChE were efficiently inhibited by these molecules, with K-i values in the range of 6.70-35.85nM for hCA I, 18.77-60.84nM for hCA II, and 0.74-4.60 for AChE, respectively.

WOS: 000467327900013, PubMed ID: 30672630, A series of novel indenopyrazole derivatives 2a-j and 3a-j were synthesized from the reaction of 1-(4-(hydroxy(1-oxo-1,3-dihydro-2H-inden-2-ylidene)methyl)phenyl)-3-phenylurea derivatives 1a-j with hydrazine and phenylhydrazine, respectively. The obtained novel indenopyrazoles (2a-j and 3a-j) were evaluated for anticancer activity against HeLa and C6 cell lines. Antiproliferative activity was determined by the BrdU proliferation ELISA assay; 2a, 2b, 2d, 2h, and 3h were found to be the most active compounds. The compounds were also screened for antimicrobial activity, and all compounds showed moderate activity against used microorganisms., Turkiye Bilimsel ve Teknolojik Arastirma Kurumu [114Z634]; Scientific and Technological Research Council of Turkey, Turkiye Bilimsel ve Teknolojik Arastirma Kurumu, Grant/Award Number: 114Z634; The Scientific and Technological Research Council of Turkey

WOS: 000462504500015, A series of novel 1,3,5-trisubstituted pyrazoline derivatives, (3aR,4S,7R,7aS)-2-[4-[1-acetyl-5-(aryl/heteroaryl)-4,5-dihydro-1H-pyrazol-3-yl]phenyl]-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindole-1,3(2H)-diones, were synthesized and evaluated for their antimicrobial and anticancer activities. In addition, the compounds were tested against acetylcholinesterase (AChE) enzyme and two physiologically relevant carbonic anhydrase I and II isozymes (hCA I and II). In this study, inhibition of hCA I and hCA II by the novel synthesized 1,3,5-trisubstituted pyrazolines was impressive, with K-i values in the range of 3.33-7.90nM for hCA I and 2.07-8.47nM for hCA II, while the K-i values of these compounds for AChE were recorded in the range of 9.61-48.42nM, respectively. Two compounds can be investigated as the leader compounds because of their lowest K-i values to make further detailed CA inhibition studies. [GRAPHICS] ., Scientific and Technological Research Council of Turkey (TUBITAK) [111T990], The authors are indebted to The Scientific and Technological Research Council of Turkey (TUBITAK Project No: 111T990) for financial supports.

WOS: 000383473800006, A series of novel racemic 2-(1,3-diaryl-3-hydroxypropyl)cyclohexan-1-ol derivatives were synthesized from 1,5-diketones. All the synthesized compounds were characterized by spectroscopic methods. The antibacterial activities of obtained chiral 1,5-diols were investigated against four Gram-positive and three Gram-negative bacteria by determining of minimum inhibitory concentrations (MICs) in vitro. Compounds 3b, 3c, and 3d were found to be active against Enterococcus faecalis and Escherichia coli. In addition, compound 3j were found to be moderately active against all tested bacterial strains., Gaziosmanpasa University [BAP-2011/94], The authors are indebted to the Gaziosmanpasa University (Grant BAP-2011/94) for financial support of this work.

WOS: 000425063500008, PubMed ID: 28792233, The new 1-(4-(3-(aryl)acryloyl)phenyl)-1H-pyrrole-2,5-diones (5a-g) were prepared from 4-aminchalcones (3a-g) and screened for biological activities. All compounds (3a-g and 5a-g), except 3d and 3e displayed good cytotoxic activities with IC50 values in the range of 7.06-67.46 mu M. IC50 value of 5-fluorouracil (5-FU) was 90.36 mu M. Moreover, most of compounds 5a-g showed high antibacterial activity with 8-20 mm of inhibition zone (19-25mm of Sulbactam-Cefoperazone (SCF)). In addition, they showed good inhibitory action against acetylcholinesterase (AChE), and human carbonic anhydrase I, and II (hCA I and hCA II) isoforms. Also, these compounds demonstrated effective inhibition profiles with Ki values of 426.47-699.58 nM against hCA I, 214.92-532.21 nM against hCA II, and 70.470-229.42nM against AChE. On the other hand, acetazolamide, clinically used drug, showed a Ki value of 977.77 +/- 227.4nM against CA I, and 904.47 +/- 106.3 nM against CA II, respectively. Also, tacrine inhibited AChE showed a Ki value of 446.56 +/- 58.33 nM., Scientific and Technological Research Council of Turkey [TUBITAK Project] [111T990], The authors are indebted to the Scientific and Technological Research Council of Turkey [TUBITAK Project No. 111T990] for financial supports.

Bu tez çalışmasında yeni bir seri 1,3-benzotiyazol türevlerinin sentezi ve antikanser aktivitelerinin incelenmesi üzerine bir çalışma gerçekleştirildi. Bunun için önce çıkış bileşikleri olan siklobütanon türevleri, norbornen ve norbornadien'e diklorketen katılıp akabinde Zn ile indirgenmesiyle hazırlandı. Siklobütanon türevlerinin benzaldehit türevleri ile reaksiyonundan α,β-doymamış karbonil bileşikleri elde edildi. Son basamakta ise α,β-doymamış karbonil bileşiklerinin, 2-aminobenzotiyol ile reaksiyonundan hedef bileşikleri olan 1,3-benzotiyazol türevleri (2-stirilbisikloalkil-1,3-benzotiyazol) sentezlendi. Sentezlenen tüm bileşikler kromatografik yöntemler ile saflaştırıldı ve yapı analizleri spektroskopik yöntemler (NMR, FT-IR) ile yapıldı. Son olarak sentezlenen bileşiklerin in vitro antikanser aktiviteleri HeLa ve C6 kanser hücrelerine karşı incelendi. Çalışmada pozitif kontrol olarak 5-fluorourasil (5-FU) kullanıldı. Sonuçlara göre bazı bileşiklerin oldukça yüksek antikanser aktiviteye sahip oldukları görülmüştür. In this thesis, a study was conducted on the synthesis of a new series of 1,3-benzothiazole derivatives and the investigation of anticancer activities. For this, cyclobutanone derivatives, the starting compounds, were prepared by dichloroketene to norbornene and norbornadiene followed by reduction with Zn. The reaction of the cyclobutanone derivatives with benzaldehyde derivatives gave. α,β-unsaturated carbonyl compounds. In the last step, 1,3-benzothiazole derivatives (2-styrylbicycloalkyl-1,3-benzothiazole), the target compounds of α,β-unsaturated carbonyl compounds reacted with 2-aminobenzothiol. All synthesized compounds were purified by chromatographic methods and structural analyzes were performed by spectroscopic methods (NMR, FT-IR). Finally, in vitro anti-cancer activities of the synthesized compounds were investigated against HeLa and C6 cancer cells. 5-fluorouracil (5-FU) was used as a positive control in the study. The results show that some compounds have very high anticancer activity. 141

WOS: 000401253900001, PubMed ID: 27780313, Benzothiazepine compounds have a wide range of applications such as antibacterial, antidepressants, anticonvulsants, antihypertensives, antibiotics, antifungal, hypnotic, enzyme inhibitors, antitumor, anticancer and anti-HIV agents. In this study, the synthesis of novel tetralone-based benzothiazepine derivatives (1-16) and their in vitro antibacterial activity and human carbonic anhydrase isoenzymes I and II ( hCA I and II) inhibitory effects were investigated. Both isoenzymes were purified by sepharose-4B-L-tyrosine-sulfanilamide affinity chromatography from fresh human red blood cells. All compounds demonstrated the low nanomolar inhibitory effects on both isoenzymes using esterase activity. Benzothiazepine derivative 2 demonstrated the best hCA I inhibitory effect with Ki value of 18.19 nM. Also, benzothiazepine derivative 7 showed the best hCA II inhibitory effect with Ki value of 11.31 nM. On the other hand, acetazolamide clinically used as CA inhibitor, showed Ki value of 19.92 nM against hCA I and 33.60 nM against hCA II, respectively., Gaziosmanpasa University, Scientific Research Projects Commission [BAP2014/33]; King Saud University, Contract Grant Sponsor: Gaziosmanpasa University, Scientific Research Projects Commission.; Contract Grant Number: BAP2014/33.; Contract Grant Sponsor: King Saud University.

WOS: 000418065300004, Novel 4,5-dihydropyrazole derivatives (3a-i), 3-(4-((3aR,4S,7R,7aS)-1,3-dioxo-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindol-2(3H)-yl)phenyl)-5-phenyl-4,5-dihydro-1H-pyrazole-1-carbothio amide, were obtained by the addition of thiosemicarbazide (2) to the chalcones (1a-i). The addition-cyclization of 2,4-dibromoacetophenone (4) to pyrazole derivatives (3a-i) gave the new pyrazolyl-thiazole derivatives (5a-i), (3aR,4S,7R,7aS)-2-(4-(1-(4-(4-bromophenyl)thiazol-2-yl)-5-phenyl-4,5-dihydro-1H-pyrazol-3-yl)phenyl)-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindole-1,3(2H)-dione. Antibacterial and acetylcholinesterase (AChE) enzyme and human carbonic anhydrase (hCA) I, and II isoform inhibitory activities of the compounds 3a-i and 5a-i were investigated. Some of the compounds showed promising antibacterial activity. In addition, the hCA II and I were effectively inhibited by the lately synthesized derivatives, with K-i values in the range of 18.90 +/- 2.37 -58.25 +/- 13.62nM for hCA II and 5.72 +/- 0.98 -37.67 +/- 5.54nM for hCA I. Also, the K-i parameters of these compounds for AChE were obtained in the range of 25.47 +/- 11.11-255.74 +/- 82.20nM. Also, acetazolamide, clinical molecule, was used as a CA standard inhibitor that showed K-i value of 70.55 +/- 12.30nM against hCA II, and 67.17 +/- 9.1nM against hCA I, and tacrine inhibited AChE showed K-i value of 263.67 +/- 91.95. [GRAPHICS] ., Scientific and Technological Research Council of Turkey (TUBITAK) [111T990], The authors are indebted to The Scientific and Technological Research Council of Turkey (TUBITAK Project No: 111T990) for financial supports.

WOS: 000397808700014, PubMed ID: 28043719, In the present study, a series of new hybrid compounds containing chalcone and methanoisoindole units 7a-n ((3aR,4S,7R,7aS)-2-(4-((E)-3-(3-aryl) acryloyl) phenyl)-3a, 4,7,7a-tetrahydro-1H-4,7-methanoisoin dole-1,3(2H)-dione) were synthesized, characterized and investigated for their anticancer activity against C6 gliocarcinoma cell in rats, and antimicrobial activity against some human pathogen microorganisms. The compounds 7e, 7h, 7j, 7k, 7L and 7n showed very high anticancer activity with the inhibition range of 80.51-97.02% compared to 5-FU. Some of the compounds exhibited anti-microbial activity. Also, they evaluated for inhibition effects against human carbonic anhydrase I, and II isoenzymes (hCA I and II) with Ki values in the range of 405.26-635.68 pM for hCA I, and 245.40-489.60 pM for hCA II, respectively. These results demonstrated that 3aR, 4S, 7R, 7aS)-2-(4-((E)-3-(3-aryl) acryloyl) phenyl)-3a, 4,7,7a-tetrahy dro-1H-4,7-methanoisoindole-1,3(2H)-dione derivatives could be used in different biomedical applications. (C) 2016 Elsevier Inc. All rights reserved.

WOS: 000362369000006, A series of novel 1,2,3,4,6-pentasubstituted-4-hydroxy-cyclohexanes (3a-u) were synthesized from the reaction of aromatic ketones with aromatic aldehydes under mild reaction conditions in good yields. The stereochemistry of the synthesized compounds was established using 1D and 2D-NMR spectra., Gaziosmanpasa University [BAP-2011/94], The authors are indebted to Gaziosmanpasa University (Grant BAP-2011/94) for financial support of this work.

Bu çalışmada; Sivas ve Tokat çiftlik sütleri ve Çamlıbel (Tokat) ve Pazar (Tokat) bölgesi toplama sütlerinden alınan örneklerde, kimyasal ve fizikokimyasal değerlerin (yağ, yağsız kuru madde, yoğunluk, protein, donma noktası, laktoz, iletkenlik), makro ve mikro elementler ile yağ asitleri miktarlarının, çiğ süttekilere göre fabrika tipi pastörizasyon (FTP) (85 oC'de 5 sn ısıtma) ve ev tipi pastörizasyonla (ETP) (kaynatmayla) değişimi incelendi. Kimyasal ve Fizikokimyasal değerler `Milkana Multi Test Ultrasonik Analiz Cihazı`, yağ asitleri Gaz Kromatografisi, makro ve mikro elementler ise ICP ile analiz eildi. Elde edilen sonuçların istatiksel analizleri, SPSS 17 istatistik programı kullanılarak faktöriyel deneme metodu ile yapıldı. Elde edilen sonuçlara ğöre, özellikle Laktoz ve Ca'un miktarlarında her iki pastörizasyon tipinde de azalma gözlenirken, diğer değerlerde çok önemli değişim olmadığı tespit edildi. Bu çalışmada elde edilen sonuçlara göre doymuş ve doymamış yağ asitleri miktarı ısıl işlemlerden etkilendiği görülmüştür. FTP işleminde çiğ süte göre toplam doymuş yağ asitleri miktari artarken toplam doymamış yağ asitleri miktarı da azalmaktadır. In this study, the four different milk samples were received from the Sivas and Tokat livestock and Çamlıbel (Tokat) and Pazar (Tokat) milk collection centres. The change of chemical and physicochemical values (fat, non-fat dry matter, density, protein, freezing point, lactose, conductivity), macro and micro element amounts and fatty acids amounts in these samples with factory-type pasteurization (FTP) (at 85 oC, heating of 5 sec.) and household by pasteurization (ETP) (traditional boiling) were examined and compared with raw milk samples. While chemical and physicochemical values were determined by Milkana Multi-Tester Ultrasonic Analyzer, fatty acids were analyzed by Gas Chromatography and macro and micro elements were measured by ICP. Statistical analysis of the obtained results were performed with SPSS 17 statistical softwarw using tha factorial experiment method. According to obtained results, especially, while the amount of lactose an Ca were decreased in both types of pasteurization, there was no significiant change in the other values. The amount of saturated and unsaturated fatty acids, based on the results obtained in this study was found to be affected by thermal treatment. While the total amount of saturated fatty acids incresed, the total amount of unsaturated fatty acids is reduced in the FTP aplication. 50

WOS: 000417435200011, A series of novel phenylurea containing 2-benzoylindan-1-one derivatives 3a - 3j were synthesized from the reaction of phenylurea-substituted acetophenones 1a - 1j with phthalaldehyde 2 under mild reaction conditions in good yields. All synthesized compounds were characterized by spectroscopic methods. The obtained compounds (3a - 3j) were evaluated for anticancer activity against HeLa and C6 cell lines. Antiproliferative activity was determined by the BrdU proliferation ELISA assay, 3f and 3g were found to be most active compounds. The compounds were also screened for antimicrobial activity and all compounds showed remarkable activity against used microorganisms., Scientific and Technological Research Council of Turkey [TUBITAK-114Z634], The authors are indebted to the The Scientific and Technological Research Council of Turkey (Grant TUBITAK-114Z634) for financial support of this work.

Bu çalışmada, öncelikle tetralon ile farklı benzaldehit türevleri bazik ortamda reaksiyona sokularak ilgili α,β-doymamış karbonil türevleri sentezlendi. Sentezlenen α,β-doymamış karbonil türevlerine Mn(OAc)3 varlığında dimedon katılması ve halkalaşması ile spiro-benzofuran türevleri elde edildi. Sentezlenen bütün bileşikler kromatografik yöntemlerle saflaştırıldıktan sonra spektroskopik metotlar (NMR, IR) kullanılarak yapıları aydınlatıldı. Son aşamada ise sentezlenen spiro-benzofuran türevlerinin insan patojeni 6 mikroorganizmaya karşı biyolojik aktiviteleri test edildi. In this study firstly, α,β-unsaturated carbonyls were synthesized from the treatment of tetralone with corresponding benzaldehyde derivatives in basic medium. Addition of dimedon to synthesized α,β-unsaturated carbonyls in the presence of Mn(OAc)3 and followed cyclization gave to the spiro-benzofuran derivatives. After the purification of the all compounds by chromatographic methods and crystallization their structure determination were using the spectroscopic methods (NMR, IR). Finally, biologically activities of spiro-benzofuran derivatives against six human pathogen microorganism were tested. 114

Bu çalışmanın ilk bölümünde, 16 adet 2-benziliden-3,4-dihidronaftalen-1(2H)-on (3a-ö) türevi 1,2,3,4-tetrahidro-1-naftalon'ün (1) oda koşullarında aromatik aldehitler (3a-ö) ile bazik ortamda muamele edilmesiyle (Claisen-Schmidt kondenzasyonu) % 45-99 arasında değişen verimlerde sentezlendi. Çalışmanın ikinci aşamasında ise elde edilen α,β-doymamış karbonil bileşiklerine 2-aminotiyofenol, etanol içerisinde ve asetik asit katalizörlüğünde reflüs edilerek katıldı. Sonuç olarak, 16 adet yeni tiyazepin türevi (5a-ö) sentezlendi. Sentezlenen tiyazepinler değişik çözücüler kullanılarak (2:1 Eter/Etanol; CH2Cl2/Hekzan) kristallendirildi. Elde edilen tüm bileşiklerin karakterizasyonu 1H-13C-NMR spektroskopisi ve FT-IR spektroskopisi yardımıyla yapıldı. Biyolojik aktivite testleri ise disk-difüzyon yöntemine göre yapıldı. Elde edilen sonuçlarda, sentezlenen bileşiklerin büyük bir çoğunluğunun baktirilere karşı aktif olduğu görüldü. Özellikle C. albicans ATCC 123 bakterisine karşı 5d, 5g, 5m bileşikleri iyi aktiviteye sahip, P. aeruginosa ATCC 9027 bakterisine karşı 5e, 5j bileşiklerinin iyi aktiviteye sahip oldukları belirlendi. In this study firstly, 16 units 2-benzylidene-3,4-dihydronaphthalene-1(2H)-one (3a-ö) derivatives were synthesized from treatment of 1,2,3,4-tetrahydro-1-naphthalone with aromatic aldehydes (2a-ö) (Claisen-Schmidt condensation) in basic medium with yields ranging from %45-99 at room conditions. In second stage of the study, 2-aminothiophenol was added to obtained α,β-unsaturated carbonyls in ethanol and acetic acid catalyst at reflux condition. Consequently, 16 novel thiazepin derivatives (5a-ö) were synthesized. Synthesized thiazepines were crystallized using different solvent systems (2:1 Ether/Ethanol; CH2Cl2/Hexane). Characterization of all the obtained compounds was performed with the aid of 1H-13C spectroscopy and FT-IR spectroscopy. Biological activity tests were performed acccording to the disk-diffusion method. In result obtained, the majority of the compounds synthesized werevfound to be active against bacteria. Especially, compounds 5d, 5g, 5m were determined to have good activity against C. albicans ATCC 123 bacteria, compounds 5e, 5j were determined to have good activity againts P. aeruginosa ATCC 9027 bacteria. 123

Bu çalışmada, 2-(stirilsiklooktil) grubu içeren yeni bir sınıf benzotiyazol türevleri dört basamakta sentezlendi. Bunun için siklookten?e diklor keten katılarak 10,10-diklorobisiklo[6.2.0]dekan-9-on elde edildi ve Zn/Asetik asit yardımıyla indirgenerek başlangıç maddesi olan bisiklo[6.2.0]dekan-9-on sentezlendi. Bisiklo[6.2.0]dekan-9-on, ilgili aldehit türevleri ile bazik ortamda muamele edilerek a,ß-doymamış karbonil bileşikleri sentezlendi. a,ß-Doymamış karbonil bileşikleri, 2-aminobenzotiyazol ile etanol içerisinde p-TsOH varlığında reaksiyona sokularak yeni 2-sübstitüe benzotiyazoller hazırlandı. Sentezlenen benzotiyazol türevleri kromatografik yöntemler ile saflaştırıldı ve spektroskopik metotlar (NMR, IR) kullanılarak yapıları aydınlatıldı ve C6 ve HeLa hücrelerine karşı in vitro anti-tümör aktivite testleri yapıldı.Anahtar Kelimeler: 2-Substitüe Benzotiyazol, Tiyazol, Antikanser, İn vitro, C6, HeLa In this study, a new class of benzothiazole derivatives containing 2-(styrylcyclooctyl) group was synthesized in four steps. Thus, 10,10-dichlorobicyclo[6.2.0]decan-9-one was prepared with addition of ketene to cyclooctene. Reduction of 10,10-dichlorobicyclo[6.2.0]decan-9-one with Zn in acetic acid gave the starting material bicyclo[6.2.0]decan-9-one. Treatment of bicyclo[6.2.0]decan-9-one with the corresponding benzaldehyde derivatives in alkaline medium afforded the a,ß-unsaturated carbonyl compounds. a,ß-unsaturated carbonyl compounds was reacted with 2-aminobenzothiazole and in the presence of p-TsOH in ethanol and prepared the novel 2-substituted benzothiazoles. Synthesized benzothiazole derivatives were purified by chromatographic methods and their structures elucidated using spectroscopic methods (NMR, IR). Finally, in vitro antitumor activities of benzothiazole derivatives were tested against C6 and HeLa cell.Keywords: 2-Substituted Benzothiazole, Thiazole, Anticancer, In vitro, C6, HeLa 92

Bu çalışmada, 2-(stirilsiklopentil) grubu içeren yeni bir sınıf benzotiyazol türevleri dört basamakta sentezlendi. Bunun için siklopenten?e diklor keten katılarak 7,7-diklorobisiklo[3.2.0]heptan-6-on elde edildi ve Zn/Asetik asit yardımıyla indirgenerek başlangıç maddesi olan bisiklo[3.2.0]heptan-6-on sentezlendi. Bisiklo[3.2.0]heptan-6-on, ilgili aldehit türevleri ile bazik ortamda muamele edilerek a,ß-doymamış karbonil bileşikleri sentezlendi. a,ß-Doymamış karbonil bileşikleri, 2-aminobenzotiyazol ile etanol içerisinde p-TsOH varlığında reaksiyona sokularak yeni 2-sübstitüe benzotiyazoller hazırlandı. Sentezlenen benzotiyazol türevleri kromatografik yöntemler ile saflaştırıldı ve spektroskopik metotlar (NMR, IR) kullanılarak yapıları aydınlatıldı ve C6 ve HeLa hücrelerine karşı in vitro anti-tümör aktivite testleri yapıldı.Anahtar Kelimeler: 2-Substitüe Benzotiyazol, Tiyazol, Antikanser, İn vitro, C6, HeLa In this study, a new class of benzothiazole derivatives containing 2-(styrylcyclopentyl) group was synthesized in four steps. Thus, 7,7-dichlorobicyclo[3.2.0]heptan-6-one was prepared with addition of ketene to cyclopentene. Reduction of 7,7-dichlorobicyclo[3.2.0]heptan-6-one with Zn in acetic acid gave the starting material bicyclo[3.2.0]heptan-6-one. Treatment of bicyclo[3.2.0]heptan-6-one with the corresponding benzaldehyde derivatives in alkaline medium afforded the a,ß-unsaturated carbonyl compounds. a,ß-unsaturated carbonyl compounds was reacted with 2-aminobenzothiazole and in the presence of p-TsOH in ethanol and prepared the novel 2-substituted benzothiazoles. Synthesized benzothiazole derivatives were purified by chromatographic methods and their structures elucidated using spectroscopic methods (NMR, IR). Finally, in vitro antitumor activities of benzothiazole derivatives were tested against C6 and HeLa cell.Keywords: 2-Substituted Benzothiazole, Thiazole, Anticancer, In vitro, C6, HeLa 134

Bu çalışmada, fenilizosiyanat türevleri (3a-e) ve 4'-aminoasetofenondan (4) çıkılarak yapılarında kinolin birimi içeren üre türevlerinin sentezi ve antimikrobiyal aktivitelerinin incelenmesi planlandı. Bu sebeple, ilk olarak, çıkış bileşikleri olan beş farklı asetofenon türevi (5a-e) fenilizosiyanat türevleri (3a-e) ve 4'-aminoasetofenonun(4) toluen içerisinde yaklaşık 12 saat reflüks edilmesi ile elde edildi. Çalışmanın ikinci basamağında ise, kalkon (1,3-diaril-2-propen-1-on) iskeletine sahip fenilüre türevleri (7a-u) ilgili asetofenonlar (5a-e) ile benzaldehit türevlerinin (6a-d) MeOH/DMSO içerisinde ve baz varlığında kondenzasyonu ile sentezlendi. Akabinde, kalkon türevlerine (7a-u) bazik ortam ve FTK (Faz transfer katalizörü: tetrabutilamonyum bromür) varlığında siklohekzanonun 1,4-katılmasıyla 1,5-diketon türevleri (8a-u) hazırlandı. Sentez kısmının son aşamasında ise 1,5-diketon türevlerinin (8a-u) etanol içerisinde amonyum asetat (NH4OAc) ile halkalaşması sonucunda hedef bileşiklerinin(9a-u) sentezi tamamlandı. Son olarak, kalkon (7a-u) ve kinolin türevlerinin (9a-u) antimikrobiyal aktiviteleri insan patojeni çeşitli mikroorganizmalara karşı Disk Difüzyon ve Makrodilüsyon teknikleri ile belirlendi.Anahtar Kelimler: Üre, Kinolin, Kalkon, 1,5-Diketon, 5,6,7,8-Tetrahidrokinolin, Antimikrobiyal, Disk difüzyon tekniği, Minimal inhibisyon konsantrasyonu. In this study, the synthesis and investigation of antimicrobial activity of urea derivatives containing quinoline unit starting from phenylisocyanate derivatives (3a-e) and 4?-aminoacetophenone (4) were planned. For this reason, firstly, five different acetophenone derivatives (5a-e) which are starting materials were obtained via refluxing phenylisocyanate derivatives (3a-e) and 4?-aminoacetophenone (4) in tolueneabout 12 hours. In second stage of study, phenylurea derivatives (7a-u) having chalcone(1,3-diaryl-2-propen-1-one) skeleton were synthesized by condensation of corresponding acetophenone (5a-e) and benzaldehyde derivatives (6a-d) in MeOH/DMSO in the presence of base. Followed, 1,5-diketone derivatives (8a-u) wereprepared by 1,4-addition of cyclohexanone to chalcone derivatives (7a-u) in the presence of PTC (Phase transfer catalyst: tetrabutylammonium bromide) in basicmedium. In the last stage of synthesis part, the synthesis of the target compounds (9a-u) were completed by cyclization of 1,5-diketone derivatives (8a-u) with ammoniumacetate (NH4OAc) in ethanol. Finally, the antimicrobial activities of chalcone (7a-u) and quinoline derivaties (9a-u) against the human pathogen different microorganismwere determined with Disc Diffusion and Macrodilution techniques.Key Words: Urea, Quinoline, Chalcone, 1,5-Diketone, 5,6,7,8-Tetrahydroquinoline, Antimicrobial, Disc diffusion assay, Minimal inhibition concentration. 198

Bu çalışmada ilk olarak 1-indanon (1) ile ilgili aromatik aldehitler (2a-e) oda şartlarında, bazik ortamda aldol kondenzasyonu (Claisen-Schmidt) yöntemiyle etkileştirilerek 2-benziliden-2,3-dihidro-1H-inden-1-on (kalkon) türevleri (3a-e)sentezlendi. Çalışmanın ikici aşamasında sentezlenen kalkon türevleri, etanol veyametanol içerisinde, malononitiril ve K2CO3 varlığında 16 saat boyunca reflüks edilmesiyle yeni 2-alkoksi siyanopiridin türevleri (4a-e, 5a-e) elde edildi. Elde edilen kalkon ve siyanopiridin türevleri kromatografik yöntemler ile saflaştırıldıktan sonra spektroskopik metotlar (NMR, IR) kullanılarak yapıları aydınlatıldı. Son olarak,sentezlenen 2-etoksi siyanopiridin türevlerinin (4a-e) antimikrobiyal aktiviteleri beş insan patojeni bakteriye karşı in vitro ortamda test edildi. Bu testlerde, pozitif kontrol olarak Penisilin G ve Seftriakson antibiyotikleri kullanıldı. Test edilen bileşiklerin MİK(minimum inhibisyon konsantrasyonu) değerleri makro dilüsyon metodu kullanılarak belirlendi. In this study, firstly, 2-benzylidene-2,3-dihydro-1H-inden-1-one (chalcone) derivates 3a-e) were synthesized by reacting 1-indanone with aromatic aldehydes (2a-e) with aldol condensation in basic medium (Claisen-Schmidt) method at room conditions. Inthe second stage of the study, new 2-alkoxy cyanopyridine derivatives (4a-e, 5a-e) were obtained, in ethanol or methanol, to reflux for 16 hours in the presence of malononitrileand K2CO3. The structures of obtained chlacone derivatives were characterized using spectroscopic methods (NMR, IR). Finally, antimicrobial activities of synthesized 2-ethoxy cyanopyridine derivates (4a-e) were tested in vitro against five human pathogenic bacteria. Penicillin G and Ceftriaxone antibiotics were used as positive control in these tests. MIC (minimum inhibition concentration) values of tested compounds were determined using macro dilution method. 100

Bu çalışmada öncelikle ilgili aromatik ketonlar (1a-c) ile aromatik aldehitler (2a-c) bazik ortamda etkileştirilerek 1,3-diaril-2-propen-1-on (kalkon) türevleri (3a-e) sentezlendi. 1,3-diaril-2-propen-1-on türevlerine (3a-e) sırasıyla asetilaseton (4), dietilmalonat (5) ve malononitril (6) % 5 mol KOt-Bu ve % 10 mol faz transfer katalizörü varlığında oda koşullarında katılarak (Michael-katılması) 1,5-diketon türevleri (7a-e, 8a-e) ve malononitril türevleri (9a-e) sentezlendi. Asetilaseton katılma türevleri (7a-e) derişik HCl içerisinde ve NH4Cl varlığında reflüks edilerek 3,5-diaril-2-siklohekzenon türevleri (10a-e) elde edilidi. Dietilmalonat katılma türevlerinin (8a-e) NH4Ac varlığında asetik asit/toluen karışımında ve asetik asit/dimetilformamit karışımında reflüks edilmesi ile sırası ile etil 2-okso-4,6-diaril-1,2,3,4-tetrahidropiridin-3-karboksilat türevleri (11a-e) ve 4,6-diaril-3,4-dihidropiridin-2(1H)-on türevleri (12a-e) sentezlendi. Malononitril katılma türevleri (9a-e) etanol içerisinde ve K2CO3 varlığında reflüks edilerek 2-etoksi-4,6-diarilnikotinonitril türevleri (13a-e) elde edildi.Son olarak, sentezlenen hetero halkalı bileşiklerin (11a-e, 12a-e ve 13a-e) antimikrobiyal aktiviteleri beş insan patojeni bakteriye karşı in vitro ortamda test edildi. Bu testlerde, pozitif kontrol olarak Penisilin G ve Seftriakson antibiyotikleri kullanıldı. Test edilen bileşiklerin MİK (minimum inhibisyon konsantrasyonu) değerleri makro dilüsyon metodu kullanılarak belirlendi. In this study firstly, 1,3-diaryl-2-propen-1-one (chalcone) derivatives (3a-e) were synthesized from the treatment of related aromatic ketones (1a-c) with aromatic aldehydes (2a-c) in basic medium. 1,5-Diketone derivatives (7a-e, 8a-e) and malononitril derivatives (9a-e) were synthesized by addition (Michael-addition) of acethylacetone (4), diethylmalonate (5) and malononitrile (6) in the presence of 5% mole KOt-Bu and 10% mole phase transfer catalyst in room temperature respectively. 3,5-diaryl-2-cyclohexenone derivatives (10a-e) were obtained by refluxing of acethylacetone addition derivatives (7a-e) in the presence of concentrated HCl and NH4Cl. Refluxing of diethylmalonate addition derivatives (8a-e) with NH4Ac in acetic acid/ toluene and acetic acid/ dimethylformamide gave the ethyl 2-oxo-4,6-diaryl-1,2,3,4-tetrahydropyridine-3-carboxylate derivatives (11a-e) and 4,6-diaryl-3,4-dihydropyridine-2(1H)-one derivatives (12a-e) respectively. 2-Ethoxy-4,6-diarylnicotinonitrile derivatives (13a-e) were obtained by refluxing of malononitrile addition derivatives (9a-e) in the presence of K2CO3 in ethanol. Finally, antimicrobial activities of synthesized heterocyclic compounds (11a-e, 12a-e and 13a-e) were tested in vitro environment against the human pathogen five bacteria. Penicillin G and Ceftriaxone antibiotics were used as positive control in these tests. MIC (minimum inhibition concentration) values of tested compounds were determined using macro dilution method. 196

Çalışmada ilk olarak siklohekzen'e oda sıcaklığında moleküler brom katılarak trans-1,2-dibrom siklohekzan elde edildi. Dibrom siklohekzan'ın etilenglikol içerisinde ve 160 °C' de KOH ile dehidbrominasyonu sonucu 1,3-siklohekzadien hazırlandı.İkinci aşamada 1,3-siklohekzadien'e maleikanhidrit diklormetan içinde 55 °C'de katılarak (Diels-Alder katılması) 3a,4,7a-tetrahidro-4,7-etano-2-benzofuran-1,3-dion elde edildi.Üçüncü aşamada, 3a,4,7a-tetrahidro-4,7-etano-2-benzofuran-1,3-dion trietilamin varlığında toluen içerisinde 4-aminoasetofenon ile 190 °C'de ıstılarak bisiklo[2.2.2]okten birimi içeren 2-(4-asetofenil)-3a,4,7,7a-tetrahidro-1H-4,7-etanoisoindol-1,3-dion sentezlendi.Çalışmanın son aşamasında, 2-(4-asetofenil)-3a,4,7,7a-tetrahidro-1H-4,7-etanoisoindol-1,3-dion ilgili benzaldehit türevleri ile bazik ortamda muamele edilerek ilgili kalkon türevleri sentezlendi.Elde edilen kalkon türevleri kromatografik yöntemler ile saflaştırıldıktan sonra spektroskopik metotlar (NMR, IR, Kütle) kullanılarak yapıları aydınlatıldı.Anahtar Kelimeler: Bisiklo[2.2.2]okten, Kalkon, Diels-Alder Reaksiyonu, İsoindol- 1,3-dion In this study, firstly, trans-1, 2-dibromocyclohexadiene was obtained by addition of molecular bromine to cyclohexene at room temperature. Dehydrobromination of 1,2-dibromocyclohexane with KOH at 160 °C in ethyleneglicol gave the 1,3-cyclohexadiene.Secondly, 3a,4,7a-tetrahydro-4,7-ethano-2-benzofuran-1,3-dione was synthesized by addition of maleic anhydride to 1,3-cyclohexadiene (Diels-Alder addition) at 55 °C in CH2Cl2.Thirdly, containing bicyclo [2.2.2]octene unit 2-(4-asetofenil)-3a,4,7,7a-tetrahidro-1H-4,7-etanoisoindol-1,3-dion which is starting material was obtained by heating of 3a,4,7a-tetrahydro-4,7-ethano-2-benzofuran-1,3-dion and 4-aminoacetophenone in the presence of triethylamine 190 °C in toluene.At the last stage, chalcone derivatives were prepared by treatment of 2-(4-asetofenil)-3a,4,7,7a-tetrahidro-1H-4,7-etanoisoindol-1,3-dion with corrosponding benzaldehyde derivatives in basic medium.The structures of obtained chlacone derivatives were characterized using the spectroscopic methods (NMR, IR, Mass).Keywords: Bicyclo[2.2.2]octene, Diels-Alder Reaction, Chalcone, Isoindol-1,3-dion 78

Bu projede, ilk olarak furan ve tiyofen halkası içeren kalkon türevleri (6a-ı), ilgili aldehit(5) ve keton türevlerinin (4) sodyum hidroksit varlığında etilalkol içerisinde, oda koşullarında aldol kondenzasyonu yoluyla sentezlendi. İkinci aşamada, sentezlenen kalkon türevlerine oda sıcaklığında aminotiyol'ün katılma reaksiyonları incelendi. Katılma reaksiyonlarında, kalkonun 3 konumunda fenil halkası olduğunda 1,4-katılma ürünleri izole edildi, furan halkası olduğunda direkt olarak halkalaşma ürünleri olan 5,7-disübstitüe-[1,4]-tiyoazepinler elde edildi. In this project, firstly, furan and thiophene ring containing chalcone derivatives were synthesized from the Aldol condensation of corrosponding aldehydes and ketones derivatives in the presence of sodium hydroxide in ethyl alcohol at room temperature.Secondly, addition reactions of aminothiol to chalcone derivatives at room temperature were investigated. In addition reactions, 1,4-additions products were isolated when 3-pozition of chalcone is phenyl ring; the direct cyclization products, 5,7-disübstitüe-[1,4]-tiyoazephine were obtained when 3- position of chalcone is furan ring. 78

Bu çalışmada, öncelikle, 9 adet kalkon türevi (4a-i) ilgili asetofenon (2) ve benzaldehit (3) türevlerinin NaOH varlığında kondenzasyonu sonucu sentezlenerek, yapıları spektroskopik yöntemler yardımıyla aydınlatıldı.Çalışmanın ikinci aşamasında, kalkon türevlerine 2-merkaptoetanol I2 katalizörlüğünde (%10 mol) metilen klorür içerisinde 1,4?katılarak ? -merkapto karbonil bileşikleri (5a-i) yüksek verimle sentezlendi. In this study, firstly, 9 chalcone derivatives (4a-4i) were synthesived by the condensation of corresponding acetophenone (2) and benzaldehyde (3) derivatives in the presence of NaOH. The structures of chalcone derivatives were elucidated using the spectroscopic methods.At the second stage of study, ? -mercaptocarbonyl compounds (5a-i) were obtained by the iodide-catalyzed (%10 mol) 1,4-addition of 2-mercaptoethanol to chalcone derivatives (4a-i) in CH2Cl2 in high yierds. 82

Bu çalışmada, fenol, 2-etoksifenol, pirokatekol, isopropilfenol ve resorsinol gibi fenol türevlerinin aluminyumisopropilat (Al(i-OPr)3) katalizörlüğünde isoeugenol ile reaksiyonundan seçimli olarak orto- pozisyondan alkillenmiş yeni fenol türevleri sentezlendi ve elde edilen bileşiklerin bazı antioksidan özellikleri incelendi.Fenol'ün isoeugenol (1:1) ile reaksiyonu %20 oranında aluminyumisopropilat katalizörlüğünde 140 oC sıcaklıkta azot atmosferi altında 3 saat ısıtılarak yapıldı. Reaksiyondan orto- ve para- alkillenmiş ürünlerin yanı sıra indan türevleri 98 ve 99 elde edildi.Bu reaksiyonların optimum şartlarını belirleyebilmek amacıyla çözücü, katalizör ve reaktantların mol oranlarını içeren bir seri çalışma yapıldı. Bu denemelerde en iyi verim 1 ekivalent isoeugenol, 2 ekivalent fenol ve %20 oranında katalizör kullanılarak çözücüsüz ortamda 140 oC sıcaklıkta azot atmosferi altında 3 saatte yapılan denemede elde edildi. Diğer fenolik bileşiklerin (pirokatekol, etoksi pirokatekol, isopropil fenol ve resorsinol) isoeugenol ile reaksiyonları da aynı şartlarda yapıldı. Fenolden 91 (%79), pirokatekolden iki izomer 92 (%35) ve 93 (%55), resorsinolden 94 (%65), etoksi pirokatekol'den 95 (%40) ve isopropil fenolden 96 (%64) izomeri elde edildi.Çalışmanın ikinci aşamasında, elde edilen yeni orto- alkillenmiş fenol türevlerinin 2,2'-azino-bis(3-etilbenztiyoazolin-6-sülfonik asit) (ABTS) radikal giderme aktivitesi, 1,1-difenil-2-pikril-hidrazil (DPPH.) serbest radikal giderme aktivitesi, süperoksit anyon radikal giderme aktivitesi, ferrik tiyosiyanat metodu ile toplam antioksidan aktivite, toplam indirgeme kuvveti gibi antioksidan aktiviteleri in vitro ortamda incelendi. In this study, the novel phenol compounds (91-99) were synthesized from the regio-selective ortho-alkylation of phenol derivatives such as phenol, 2-ethoxyphenol, pyrocatechol, 2-isopropyl phenol and resorcinol by isoeugenol in the presence of aluminium isopropoxide (Al(i-OPr)3), and some of their antioxidant properties were investigated.The reaction of phenol (2) with isoeugenol (1) (in ratio of 1:1) was carried out using the aluminium isopropoxide (20% mol) as catalyst in solvent free conditions at 140 oC for 3 hours under N2 atmosphere. The reaction gave four products: ortho-alkylated product (91) (25%), para-alkylated product (97) (6%) and indane derivatives (98) (22%) and (99) (9%) arising from isoeugenol.To establish the optimal conditions, we carried out a set of experiments varying the catalyst, solvent and molar ratios of the reagents. The best yield of the ortho-alkylated product 91 (79%) was obtained when 20 mol % of Al(i-OPr)3, 2 equivalent phenol and 1 equivalent isoeugenol were stirred at 140 oC for 3 hours in solvent free conditions.The reaction of isoeugenol with phenol derivatives pyrocatechol, resorcinol, 2-ethoxyphenol and 2-isopropylphenol was carried out under the same conditions. The reactions yielded the compound 91 from phenol, two isomer 92 and 93 from pyrocatechol, 94 from resorcinol, 95 from 2-ethoxyphenol and compound 96 from 2-isopropylphenol.In the second stage of study, the antioxidant properties of new ortho- alkylated phenol derivatives (91-99) were evaluated with in vitro methodologies such as (2,2?-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) ABTS?+ radical scavenging activity, (1,1-diphenyl-2-picryl-hydrazyl) DPPH. free radical scavenging activity, super oxide anion radical (O2.-) scavenging activity, total antioxidant activity by ferric thiocyanate method and total reducing power by sodium ferricyanide reduction method. 132

Hem doğal hemde sentetik olarak elde edilebilen kalkonlar flavonoid ailesine üye bileşikler olup geniş bir biyolojik aktivite spektrumuna sahiptirler. Bu yüzden, son yıllarda kalkon ve türevleri yoğun bir ilgi odağı olmuş ve özellikle biyolojik aktivite üzerine çok sayıda çalışma yapılmıştır.Bu çalışma da ilk olarak; farklı asetofenon türevleri (2a-ö) ve furfural (3) bazik ortamda etkileştirilerek toplam 17 adet kalkon türevinin sentezi gerçekleştirildi.2a-ö 3 4a-öX = o, m, p-Br ; o, m, p-Cl ; o, m, p-OCH3; o, p-OH; o, m, p-NO2, m, p-NH2, p-CH3İkinci kısımda ise sentezlenen kalkon türevlerine (4a-m) tiyofenol'ün (5) baz katalize çözücüsüz ortamda 1,4- katılması (Michael Katılması) tepkimesi sonucunda 14 adet tiyofenol katılma ürünü sentezlendi.4a-m 5 6a-mX = o, m, p-Br ; o, m, p-Cl ; o, m, p-OCH3; o, p-OH; o, m, p-NO2Üçüncü basamakta kalkon türevlerine (4a-j) tiyoglikolik asitin (7) çözücüsüz ortamda baz katalize 1,4- katılması gerçekleştirildi ve 11 adet bileşik elde edildi.4a-j 7 8a-jX = o,m,p-Br ; o,m,p-Cl ; o,m,p-OCH3; o,p-OHDördüncü olarak kalkon türevlerine (4a-j) metiltiyoglikolat (9) CH2Cl2 içerisinde iyot katalizörlüğünde katıldı ve 11 adet bileşik elde edildi.4a-j 9 10a-jX = o, m, p-Br ; o, m, p-Cl ; o, m, p-OCH3; o, p-OHSon basamakta, kalkon türevlerinin ve tiyofenil katılma ürünlerinin biyolojik aktiviteleri, insan patojeni 12 ayrı mikroorganizmaya karşı test edildi. Bu testlerde pozitif kontrol olarak SCF (Sepaferazon / Sulbactam), negatif kontrol olarak ta CH3OH (metanol) kullanıldı ve testler disk-difüzyon yöntemine göre yapıldı.Anahtar kelimeler: Kalkon, tiyofenol, tiyoglikolik asit, metiltiyoglikolat, biyolojikaktivite, insan patojeni mikroorganizma. Chalcones can be obtained as either natural or synthetic are belonging to the flavanoid family and they have largly biological activity. Therefore, many investigations have been done on the chalcone derivatives in last years.In this study, seventeen chalcone derivatives (4a-ö) were firstly synthesized from the treatment of furfural (3) and substitue acetophenones (2a-ö) in the presence of base.2a-ö 3 4a-öX = o, m, p-Br ; o, m, p-Cl ; o, m, p-OCH3; o, p-OH; o, m, p-NO2, m, p-NH2, p-CH3Secondary, thiophene addition products (6a-m) were obtained from the base catalyzed 1,4-addition (Michael Addition) of thiophene (5) to chalcone derivatives (4a-m) under the solvent-free conditions.4a-m 5 6a-mX = o, m, p-Br ; o, m, p-Cl ; o, m, p-OCH3; o, p-OH; o, m, p-NO2In the third stage of study, the base catalyzed 1,4-addition of thioglicolic acid (7) to chalcone derivatives (4a-j) were carried out under the solvent-free conditions and eleven adduct products were yielded in this reaction.4a-j 7 8a-jX = o,m,p-Br ; o,m,p-Cl ; o,m,p-OCH3; o,p-OHFourth, eleven methylthioglycolat (9) adduct products were synthesized by the iodine catalyzed reaction of methylthioglycolat (9) with chalcone derivatives (4a-j) in CH2Cl2 at room temperature for 0.5-3 hours.4a-j 9 10a-jX = o, m, p-Br ; o, m, p-Cl ; o, m, p-OCH3; o, p-OHLastly, the biological activities of chalcone derivatives and products of thiophenol adduct were screened aganist the human pathogen 12 different microorganism. In this tests, SCF (Sepaferazon / Sulbactam) was used as positive control and CH3OH (methanol) was used as negative control, and the tests were done in according to the discs-diffusion method.Keywords: Chalcone, thiophene, thioglicolic acid, methylthioglycolat, biological activitie, human pathogen microorganism 212

Bu çalışmada öncelikle, 2,4-diaril-5,6,7,8-tetrahidrokinolin türevlerinin (6) sentezi için gerekli başlangıç bileşikleri olan kalkon türevleri (3), ilgili asetofenon (1) ve benzaldehit türevlerinin (2) bazik ortamdaki kondenzasyonu sonucu sentezlendi.Projenin ikinci basamağında 1,5-diketon türevlerinin (5) sentezi, ilk basamakta elde edilen kalkon türevlerine (3) siklohekzanon'un (4) bazik ortamda 1,4 katılması sonucu gerçekleştirildi.Çalışmanın sentez kısmının son aşaması olan 2,4-diaril-5,6,7,8-tetrahidrokinolin türevlerinin (6) sentezi ise, ikinci aşamada elde edilen 1,5-diketon türevlerinin (5) asetik asit içerisinde amonyum asetat (NH4OAc) varlığında reflüks edilerek halka kapatma reaksiyonu sonucu gerçekleştirildi.Elde edilen 2,4-diaril-5,6,7,8-tetrahidrokinolin türevlerinin (6) biyolojik aktiviteleri insan patojeni 12 farklı mikroorganizmaya karşı disk difüzyon tekniği ile belirlendi. Bileşiklerin her biri ayrı ayrı metanolde çözülerek 5.2 mg/ml'lik stok çözeltisi hazırlandı. Bu çözeltinin 20 µL'si NA (Nutrient Agar) hazırlanmış petri kaplarında inokülasyonu yapılmış bakteriler üzerine yerleştirilmiş diskler üzerine emdirildi. 18 saatlik süre sonunda diskler etrafında oluşan zonlar (mm cinsinden) ölçüldü.Anahtar Kelimler: Kalkon, 1,5-diketon, kinolin, 2,4-diaril-5,6,7,8-tetrahidrokinolin,antibakteriyel, halka kapatma reaksiyonu, disk difüzyon tekniği. In this study, firstly, chalcone derivatives (3) that is starting compounds for synthesis of 2,4-diaryl-5,6,7,8-tetrahydroquinoline derivatives (6) were synthesized by condensation of corresponding acetophenone (1) and benzaldehyde derivatives (2) in basic condition.In second stage of study, 1,5-diketone derivatives (5) were obtained by 1,4 addition of cyclohexanone (4) to chalcone derivatives (3) in basic condition.The synthesis of 2,4-diaryl-5,6,7,8-tetrahydroquinoline derivatives (6), which is the last stage of synthesis part, was carried out by the ring closing reaction of 1,5-diketone derivatives (5), with amonnium acetat (NH4OAc) in acetic acid.The biological activities of obtained 2,4-diaryl-5,6,7,8-tetrahydroquinoline derivatives (6) were determined against the human pathogen 12 different microorganism with disc diffusion assay. Each of the compounds was dissolved in methanol and 5.2 mg/ml dilution was prepared. 20 µL of this dilution was made absorb on the disk placed on inokulated bacterias in petri container prepared NA (Nutrient Agar), and the zones constituting around the discs was measured end of the 18 hours.Key Words: Chalcone, 1,5-diketone, quinoline, 2,4-diaryl-5,6,7,8-tetrahydroquinoline,antibacterial, ring closing reaction, disc diffusion assay. 180

Kalkonlar flavonoid ailesine üye doğal ya da sentetik bileşiklerdir. Kimyasal olarak, üçkarbonlu bir α, β-doymamış karbonil sistemiyle birbirine bağlanan iki aromatik halkadan(1,3-diaril-2-propen-1-on iskeleti) oluşurlar. Bitkilerden izole edilen ve kimyasal olaraksentezlenen pek çok kalkon türevi geniş bir biyolojik aktiviteye sahiptir. Bu yüzden kalkontürevleri üzerine çok sayıda araştırma yapılmaktadır.Bu çalışmada öncelikle, 11 adet kalkon türevi (12a-j) benzaldehit (15) ve sübstitüeasetofenonların (14a-j) oda sıcaklığında, etanol içerisinde, NaOH ile etkileştirilmesisuretiyle sentezlendiler.OO OCH3 H NaOH, EtOH+25 0C, 3saatXXX = -H, 2-OH, 4-OH, 2-Cl, 3-Cl, 4-Cl, 2-Br, 3-Br, 2-OCH3, 3-OCH3, 4-OCH3Çalışmanın ikinci aşamasında, hetero halkalı ve polifonksiyonel bileşiklerin sentezindeönemli bir ara ürün olan 1,5-diketon türevleri (17a-g), siklohekzanonun (16) sekiz kalkontürevine (12a-g) çözücüsüz ortamda faz transfer katalizörü (% 6 mol) ve KOH (% 6 mol)varlığında, 1,4-katılmasıyla oda sıcaklığında sentezlendi.O O O O% 6 molKOH% 6 mol C6H5N(C2H5)3Cl-+X XX = -H, 2-Cl, 3-Cl, 4-Cl, 2-Br, 2-OCH3, 3-OCH3, 4-OCH3Anahtar Kelimeler: 1,3-diaril-2-propen-1-on, kalkon, α, β-doymamış keton, 1,5-diketon. Chalcones are natural or synthetic compounds belonging to the flavonoid family.Chemically, they consist of two aromatic rings are joined by a three-carbon α, β-unsaturated carbonyl system (1,3-diaril-2-propen-1-on). Both extracted from plants andchemical synthesized most chalcone derivatives have largely biologically active.Therefore, many investigations have been done on the chalcone derivatives.In this study, firstly, eleven chalcone derivatives (12a-j) were synthesized from thebenzaldehyde (15) and substitue acetophenones (14a-j) by treatment with NaOH in ethanolat room temperature.OO OCH3 H NaOH, EtOH+25 0C, 3saatXXX = -H, 2-OH, 4-OH, 2-Cl, 3-Cl, 4-Cl, 2-Br, 3-Br, 2-OCH3, 3-OCH3, 4-OCH3In the second stage of study, 1,5-diketone derivatives (17a-g) which are importantintermediates in the synthesise of heterorings and polyfunctional compounds, synthesizedfrom the 1,4-addition of cyclohexanone (16) to the eight chalcone derivatives (12a-g)under the solvent-free conditions and exist phase transfer catalysis (6% mole) andpotassium hydroxide (6% mole) at room temperature.O O O O% 6 molKOH% 6 mol C6H5N(C2H5)3Cl-+X XX = -H, 2-Cl, 3-Cl, 4-Cl, 2-Br, 2-OCH3, 3-OCH3, 4-OCH3Keywords: 1,3-diaryl-2-propen-1-on, chalcone, α, β-unsaturated ketone, 1,5-diketone. 121

Bu çalışmada, 1-(2-klorosiklohept-1-en-1-il)benzen (48) ve 1-(2-klorosiklohept-2-en-1-il)benzen (49)'den çıkılarak, 1-siklohept-1,2-dien-1-ilbenzen'in (18) sentezi üzerineçalışıldı.Öncelikle, 2-fenilsikloheptanon'un PCl5 ile reaksiyonundan başlangıç bileşikleri olan 48ve 49 sentezlendi.Ph Ph PhO Cl ClPCl5+CCl450 48 49İkinci aşamada, çıkış bileşikleri 48 ve 49'un kapalı tüp ve 1850C'de KOtBu ilereaksiyonları incelendi. Her iki reasiyonda da HCl eliminasyonu ile oluşan 1-siklohept-1,2-dien-1-ilbenzen'in (18) dimerleşme ürünleri olan 51 ve 52 izole edildi.PhClKapali tüp PhKOt-Bu/Benzen1850C48 +Ph PhPhCl 1828Kapali tüp 27KOt-Bu/Benzen1850C49İlave olarak; vinil klorürler 48 ve 49'un aynı şartlarda, DBI varlığında KOtBu ilereaksiyonları araştırıldı. Bu reaksiyonlardan da, 1-siklohept-1,2-dien-1-ilbenzen'in (39)DBI ile [4+2] katılma ürünleri 57 ve 58 izole edildi.PhPhCIKapalı tüp 57OPhKOtBu / Benzen PhDBI,1850C48 PhPhPhCIKapalı tüp 58O18KOtBu / BenzenPhDBI,1850CPh49Anahtar Kelimeler:Allen, dimerleşme, dehidrohalojenasyon, 1-Siklohept-1,2-dien-1-ilbenzen. In this study, the synthesis of 1-cyclohept-1,2-dien-1-ylbenzene (18) from vinyl clorides,1-(2-chlorocyclohept-1-en-1-yl)benzene (48) and 1-(2-chlorocyclohept-2-en-1-yl)benzene (49), was studied.Fistly, the starting compounds, 1-(2-chlorocyclohept-1-en-1-yl)benzene (48) and 1-(2-chlorocyclohept-2-en-1-yl)benzene (49), were synthesized from the reaction of 2-phenylcycloheptanone (50) with PCl5 .Ph Ph PhO Cl ClPCl5+CCl450 48 49Secondly, the reactions of the starting compounds 48 and 49 with KOtBu in sealed tube,at 1850C were examined. [2+2] Dimerization products 51 and 52 of 1-cyclohept-1,2-dien-1-ylbenzene 18 were isolated from the each reactions.PhClSealed tube PhKOt-Bu/Benzene1850C48 +Ph PhPhCl 1828Sealed tube 27KOt-Bu/Benzene1850C49Additionaly; in the same conditions, the reactions of vinyl clorides 48 and 49 withKOtBu in the presence of DBI were investigated. [4+2] Addition products, 57 and 58, of1-cyclohept-1,2-dien-1-ylbenzene (18) with DBI were isolated from the each reactions.PhPhCI57Sealed tube OPhKOtBu / BenzenePhDBI,1850C48 PhPhPhCISealed tube 39 58OKOtBu / Benzene PhDBI,1850C49 PhKey Words:Allene, dimerization, dehydrohalogenation, 1-Cyclohept-1,2-dien-1-ylbenzene. 59

II ÖZET l-FENİLSİKLOHEPTA-l,2-DİEN'İN SENTEZİ VE YAKALANMASI ÜZERİNE ÇALIŞMALAR Yakup BUDAK Gaziosmanpaşa Üniversitesi Fen Bilimleri Enstitüsü Kimya Anabilim Dalı Bu çalışmada, önce l-fenil-l,2-sikloheptadien'in (100) sentezi için çıkış bileşikleri olan 7,7-dibrom-l-fenilbisiklo[4.1.0]heptan (101), 2,3-dibrom-l-fenilsiklohepten (102), 1-iyot- 2-fenilsiklohepten (103) ve 1 -iyot-7-fenilsiklohepten (104) bilinen yöntemlerin uygulanmasıyla sentezlendi. Br Ph Y Ph em 101 102 103 104Ill l-İyot-2-fenilsiklohepten (103) ve l-iyot-7-fenilsiklohepten'in (104) sentezi için sikloheptanon (105) başlangıç maddesi olarak kullanıldı. Sikloheptanon fenilmagnezyum bromür (PhMgBr) ile muamele edilerek 1-fenilsikloheptanol'e (106) dönüştürüldü. 1- Fenilsikloheptanol'den (106) p-TsOH yardımıyla H2O çıkarılarak 1 -fenilsiklohepten (107) elde edildi. 107'nin hidroborasyonu ve oksidasyonunu takiben piridinyumklorokromat (PCC) ile yükseltgenmesiyle 2-fenilsikloheptanon (109) sentezlendi. 2-Fenilsikloheptanon (109) hidrazin hidrat ile izomerik (Syn ve anîî) hidrazon 110'a dönüştürüldü. Hidrazon 110'un I2 ile reaksiyonundan l-iyodo-2-fenilsiklohepten (103) ve l-iyodo-7- fenilsiklohepten (104) izole edildi. Vinil iyodürler 103 ve 104'ün ayrı ayn potasyum tersiyer butoksit (KO/-Bu) ile reaksiyonundan l-fenil-l,2-sikloheptadien'in (100) dimerleşme ürünleri olan 113 ve 114 izole edildi. Yine, 103 ve 104'ün ayrı ayrı difenilizobenzofuran (DBI) varlığında KO-Bu ile 180 °C'de kapalı tüpte yapılan reaksiyonda l-fenil-l,2-sikloheptadien'in (100) katılma ürünleri endo 115 ve exo 116 elde edildi. 1-Fenilsiklohekzen'e (121) hekzan içerisinde dibrom karben katılarak, katılma ürünü 7,7- dibromo-l-fenilbisiklo[4.1.0]heptan'in (101) sentezi gerçekleştirildi. 101'in Aseton / H2O içerisinde Ag^ varlığında ile düzenlenmesiyle 2-bromo-l-fenilsiklohept-2-enol (131) ve 2- bromo-3-fenilsiklohept-2-enol (130) izole edildi. 130'un PBr3 ile reaksiyonu 2,3-dibromo- 1-fenilsiklohepten'i (102) verdi. Bu bileşiğin Zn ile reaksiyonu hedeflenen ailen 100 yerine Wurtz-tipi kenetlenme ürünleri olan 133 ve 134*ü verdi. Ayrıca, karben katılma ürünü 101'in t-BuLi ile reaksiyonundan ailenin dimerleşme ürünleri 113 ve 114'ün yerine insersiyon ürünleri 136 ve 137 elde edildi. Anahtar Kelimeler; Ailen, eliminasyon, izomerizasyon, dehidroiyodinasyon, debrominasyon, insersiyon, karbenoid, Wurtz-tipi kenetlenme, siklo katılma. IV ABSTRACT STUDIES ON SYNTHESIS AND TRAPPING OF l-PHENYLCYCLOHEPT-l,2-DIENE Yakup BUDAK Gaziosmanpaşa University Graduate School of Natural and Applied Science Department of Chemistry Dactorate Thesis 2005, 115 pages Supervisor Jury Jury Jury Jury Assoc. Prof. Dr. Mustafa CEYLAN Prof. Dr. Yavuz TAŞKESENLİGİL Prof. Dr. Adem ÖNAL Prof. Dr. Osman ÇAKMAK Assoc. Prof. Dr. Nurullah SARAÇO?LU In this study, firstly, 7,7-Dibromo-l-phenylbicyclo [4.1.0] heptane (101), 2,3-dibromo-l- phenylcycloheptene (102), l-iyodo-2-phenylcycloheptene (103) and l-iyodo-7- phenylcycloheptene 104, which are precursors at 1 -phenyl- 1,2-cycloheptadien (100) were synthesized using well known methods. 100V Cycloheptanone (105) were used as a starting material for the synthesis of l-iyodo-2- phenylcycloheptene (103) and l-iyodo-7-phenylcycloheptene (104), treatment of cycloheptanone (105) with phenylmagnesium bromide (PhMgBr) gave the 1- phenylcycloheptanol (106). Dehydration of the 1 -phenyl cycloheptanol (106) with p-TsOH afforded the 1 -phenyl cycloheptene(107). Hydroboration of 107 followed by oxidation with PCC yielded 2-phenylcycloheptanone (109), which was converted to the isomeric hydrazone 110 by treatment of hydrazine hydrate. Reaction of the isomeric hydrozone 110 with I2 resulted in the formation of l-iyodo-2-phenylcycloheptene 103 and l-iyodo-7- phenylcycloheptene 104. Dimerization products [2 + 2] at 113 and 114 of 1 -phenyl- 1,2-cycloheptadien (100) were isolated from the reaction of vinyl iodides 103 and 104 with KO/-Bu, seperately at 180 °C in a sealed tube. In addition, the adducts endo 115 and exo izomer 116 of 100 were obtained in from the reaction of 103 and 104 with KO/-Bu seperately in the presence of DBI at 1 80 °C in a sealed tube. In this stage of the study, addition of dibromocarbene to 1-phenylcyclohexene (124) in hexane afforded 7,7-dibromo-l-phenylbicyclo[4.1.0]heptane (101). The rearrangement of (101) in acetone/H20 in the presence of Ag+ ion resulted in the formation of alcohols (130) and (131). 2,3-Dibromo-l-phenylcycloheptene (102) was obtained from the reaction of alcohol 130 with PBr3. Treatment of 102 with activated zinc gave the condensation products 133 and 134 instead of the expected ailene 100. The reaction of carben addition product 101 with t-BuLi gave the insertion products 136 and 137 instead of the dimerization products 113 and 114 of ailene 100. Key Words: Ailene, elimination, isomerization, deiodination, debromination, insertion, carbenoid, Wurtz-like condensation, cycloadduct. 130

ÖZET l-FENİLSÎKLOHEKZA-l,2-DİEN'İN SENTEZİ ÜZERİNE BİR ARAŞTIRMA İrfan ÖZDEMİR Gaziosmanpaşa Üniversitesi Fen Bilimleri Enstitüsü Kimya Anabilim Dalı Yüksek Lisans Tezi 2002,...< sayfa Danışman : Y.Doç. Dr. Mustafa CEYLAN Jüri : Y.Doç. Dr. Mustafa CEYLAN Gerilimli 1,2-siklohekzadienin (4) bir türevini sentezlemek için 1-fenilsiklohekzen (69), bilinen yöntemlerle sentezlendi. 69 bileşiğinin hidroborasyonu ve H2O2 ile yükseltgenmesi 2-fenüsiklohekzanol' ü (70) verdi. 70 'in PCC ile yükseltgenmesi ile 2- fenilsiklohekzanon (71) elde edildi. 2-Fenil-l-iyodosiklohekzen (73) ve 3-fenil-2- iyodosiklohekzen (74); keton 71' in hidrazinyumhidrat, iyot ve Net3 ile muamele edilmesi ile elde edildiler. 73 Bileşiği düşük sıcaklıkta (65-70°C ) t-BuOK ile reaksiyon vermedi. Bununla beraber, 73' ün t-BuOK ile 165°C eliminasyon reaksiyonu verdiği gözlendi. Ayrıca 74' ün- t-BuOK ile reaksiyonu 73'e izomerizasyon ve az miktardada elimasyon ile sonuçlandı. Anahtar kelimeler: Ailen, eliminasyon, izomerizasyon 11 ABSTRACT A RESEARCH ON SYNTHESIS OF 1-PHENYLCYCLOHEX-U-0IENE İrfan ÖZDE M İ R Gaziosmanpaşa University Graduate School of Natural and Applied Science Department of Chemistry Masters Thesis 2002,.».pages Supervisor : AsstProf.Dr.Mustafa CEYLAN Jury : AsstProf. Dr. Mustafa CEYLAN * MMIMU«lttW«ltMtMHtt*«tNM«MWM«i In order to synthesize a phenyl derivative of strained 1,2-cyclohexadiene (4), firsty 1-phenylcyclohexene (69) which is a starting material was synthesized by the known methods. Hydroboration of 69 followed by H2O2 oxidation gave 2-phenylcyclohexanole (70). The oxidation of 70 with PCC afforded the corresponding ketone 2- phenylcyclohexanone (71). 2-Phenyl-l-iodidecyclohexene (73) and 3-phenyl-2- iodidecyclohexene (74) were obtained by means of treatment of ketone 71 with hydraziniumhydrate, iodine andNEt3. The reaction of 73 with t-BuOK at low temparature ( 65-70°C ) did not react. However, the treatment of 73 with t-BuOK at 165°C gave elimation of HI, and the reaction of 74 with t-BuOK was resulted in the isomerization to 73 and the elimination of HI. Key Words; Ailene, elimination, isomeritarion. 45

Bu çalışmada, halkalı ketonlar ve a-metil, fenil sübstitüe halkalı ketonlann PBr5 ile reaksiyonlan ve bu reaksiyona sübstitüentlerin etkisi araştınldı. Bu amaçla, a- fenilsiklohekzanon (65), -heptanon (66), a-metilsiklopentanon (81), -hekzanon (19) ve -heptanon (82) bilinen yöntemler ve bu yöntemlerin modifiye edilmesiyle sentezlendi. Ph 65 Ph ^K^P /n^o ch3 u (y U 66 81 19 82 Siklopentanon (43), -hekzanon (1) ve -heptanon (51)' in PB15 ile reaksiyonlan yüksek verimlerle a- katılma (haloform tipi) ürünlerini (60,61,62) verdi. Bu sonuçlara göre Br atomunun enol üzerinden reaksiyona girdiği tesbit edildi.& 60 O 61 a 62 2-Fenilsiklohekzanon (65) ve -heptanon (66)' nın PBrs ile reaksiyonlarında da 3 unsaturated ketone (90) as a result of HBr elimination reaction. CHa^Br 85,86 87,88 90 Key Words: a-Phenyl ketone, a-Methyl ketone, PBrs, PCls, PCC, Substition Reaction 87

ÖZET l-FENİLSİKLOHEKZA-l,2-DİEN'İN SENTEZİ VE l-(2,3-DİBROMOSİKLOHEKZ -1-EN-1-İL)BENZEN'İN METALİK ÇİNKO İLE REAKSİYONU Yakup BUDAK Gaziosmanpaşa Üniversitesi Fen Bilimleri Enstitüsü Kimya Anabilim Dalı Yüksek Lisans Tezi 1999, 63 sayfa Danışman : Y.Doç. Dr. Mustafa CEYLAN Jüri : Y.Doç. Dr. Mustafa CEYLAN Jüri : Yrd.Doç.Dr. Bülent BÜYÜKKTOAN Jüri : Yrd.Doç.Dr. Hayati SARI Bu çalışmada, ilk olarak siklopentanon (105) PhMgBr ile etkileştirilerek 1-fenil- siklopentanol (106) 'a dönüştürüldü. 106'dan P-TsOH yardımıyla bir mol su elimine edilerek 1-siklopent-l-en-il benzen (109) elde edildi. Alken 109'a dibrom karben katılarak 6,6- dibromo-l-fenilbisiklo[3.1.0]hekzan (110) sentezlendi. 110 bileşiğinin 150 °C 'de l-(2,3- dibromosiklohekz-l-en-il)benzen (116)'e, 180°C 'de ise bifenil (112)'e dönüştüğü gözlendi. Yine 110'un AgN03 ile solvolizi 2-bromo -3-fenil siklohekz -2-en-l-ol (lll)'u verdi. Dibrom 116 'nın Zn ile reaksiyonu beklenen ailen 117'nin yerine Wurtz-tipi iki kenetlenme ürünü verdi. Ayrıca, 116 Zn - asetik asit ve LiAfflU ile indirgenerek l-(2-bromosiklohekz-2-en-l- il)benzen (120) 'ye dönüştürüldü. 120 'nin t-BuOK ile reaksiyonunda elde edilen hidrokarbonun bifenil olduğu ^-NMR ve 13C-NMR analiziyle tesbit edildi. Buda ailen 117'nin oluştuğunun bir işaretidir. Anahtar kelimeler: Allen, solvoliz, wurtz-tipi kenetlenme ABSTRACT 1-PHENYLCYCL0HEX-1,2-DIENE OF SYNTHESIS AND l-(2,3-DIBROMOCYCLOHEX -1- EN-1-YL)BENZENE OF METAL ZINC WITH REACTION Yakup BUDAK Gaziosmanpaşa University Graduate School of Natural and Applied Science Department of Chemistry Masters Thesis 1999 63 pages Supervisor : Asst.Prof.Dr.Mustafa CEYLAN Jury : AsstProf-Dr.Mustafa CEYLAN Jury : AsstProf.Dr. Bülent BÜYÛKKD3AN Jury : AsstProf.Dr.Hayati SARI In this study, at the first time the treatment of cyclopentanon (105) with phenyl- magnesiumbromide (PhMgBr) followed by dehydration with 4-toluenesulfonic acid(P- TsOH) gave the alkene 1-cyclopent-l-en-yl (109). The product 6,6-dibromo-l- phenlybicyclo [3.1.0] hexane (110) was synthesized by the addition of dibromo- carbene to the alkene 109. The rearrengement of 109 whit at different temparetures ( 150 °C and 180 °C) yielded the l-(2,3-dibromocyclohex -1- en-l-yl)benzen (116) and the bifenil 112, respectively., Silver ion-catalyzed solvolysis of 110 gave the 2-bromo-3-phenlycyclohex-2-en-l-ol (111) The reaction of 116 with Zn afforded the two wurtz-like coupling products instead of expected allene 117. The compound l-(2-bromocyclohex-2-en-l-yl)benzene (120) was transformed by the seduction of 116 with Zn- Acetic Acide and LİAIH4. The product which is a hidrocarbon abtained by the reaction of 120 with t-BuOK was determined to be biphenly by 13C NMR Spectralanalysis. This result is a evidence of ailene 117 formation. Key Words: Ailene, solvolysis, wurtz-like coupling 74