1,3-difenil-4,5-bis(hidroksiimino)-imidazolidin ve Ni(II), Cu(II), Pd(II), UO2(VI) komplekslerinin sentezi

Abstract

Antitümör etkileri incelenmekte olan vic-dioksimlerle, terapötik etkilerden ötürü kullanım alanı bulan imidazolidin türevleri ayrı ayrı birçok çalışmaya konu olmuştur. Bu iki fonksiyonel gurubun bir arada bulunması halinde, her ikisinin özelliklerini ortak olarak bulundurabilecek yeni bir ligandın sentezi ve geçiş metalleriyle oluşturduğu komplekslerin incelenmesi bu çalışmanın esasını oluşturmaktadır. Bir sekonder amin olan N,,N'-difenilmetandiamin ile dikloroglioksim, aşırı NaHCO3 ihtiva eden etanol çözeltisinde reaksiyona sokulup 5-üyeli heterosiklik imidazolidin halkasının vic-dioksim türevi elde edilmiştir. l,3-difenil-4,5-bis(hidroksiimino)imidazolidin (LH2) ligandının elementel analizi C15H14N4O2 kapalı formülüne çok iyi uymaktadır. Kütle spektrumunda 282 de çıkan moleküler iyona ait pik, ligandın molekül ağırlığını kesin olarak belirlemektedir. 1H-n.m.r. spektrumunda nispeten zayıf olana (10.7 ppm) kaymış olan oksim OH protonlarına ait geniş singlet ve i.r. spektrumunda 3340 ve 2800-2600 cm-1 de çıkan bandlar Lh2'de oksim protonları ile halkadaki N atomları arasında bir H köprüsünün (0-H...N) mevcudiyetini göstermektedir. Anti- formundaki ligandın bu H-köprülerinin yapıya kazandırdığı kararlılıktan ötürü amphi-formuna dönüşümü mümkün olamamaktadır. LH2'nin Ni(II), Co(II), Cu(II), Pd(II) ve U02(VI) metal iyonları ile vermiş olduğu kompleksler izole edilmiş, hepsinde de metal/ligand oranının 1:2 olduğu elementel analiz sonuçlarından anlaşılmıştır. Beşli imidazolidin halkasından ileri gelen gerginlik nedeniyle, vicdioksim gurubunda N...N mesafesi arttığından, nikel(II) kompleksi, beklenilen kare-düzlemsel yapıdaki kırmızı bileşik olmayıp, magnetik susseptibilite ölçümlerinden de anlaşıldığı gibi, tetrahedral N,0-şelatı halindedir. Co( II) kompleksinde iki vig-dioksim gurubu N,N'-şelatı yaparak bir kare düzlem oluşturmakta, i.r. spektrumuyla da belirlenen H2O molekülü kare-piramidin tepesinde yer almaktadır. Magnetik momentinin 3.72 BM olması da bu yapıyı doğrular. LH2'nin Cu(II), Pd(II) ve U02(VI) kompleksleri ise kare düzlemsel yapıdadır. N,N-şelatı oluşumu yanında 0-H...0 köprülerinin de meydana geldiği i.r. spektrum- larında 1760 cm-1de görülen zayıf bending titreşimlerinden anlaşılmıştır. Sonuç olarak, beşli imidazolidin halkasından ötürü 1, 3-difenil-4,5-bis(ihidroksiimino)imidazolidin' in gergin bir yapıya sahip olup, bu özellik nikel(II) ile diğer vic-dioksimlerde olduğu gibi kare-düzlemsel değil, tetrahedral bir kompleks vermesine yol açmıştır. İmidazolidin ve vic-dioksimlerin son yıllarda ilgi çeken terapötik etkileri nedeniyle LH2'nin bu yönden de araştırılması uygun olacaktır.

Anti-dichloroglyoxime and cyanogen-di-N-oxide, which is prepared by treating anti-dichloroglyoxime with alkali, have been used frequently in order to prepare vic-dioxime derivatives. When diamino compounds react with these two reactants heterocyclic or macro-hetero- cyclic dioximes are obtained. The first five-membered heterocyclic vic-dioxime, l,3-diphenyl 1-2-thioxo-4,5-bis (hydroxyimino)-imidazoline, was synthesized by the reaction of diphenylthiourea with cyanogen-di-N-oxide. l,4-diphenyl-1-2, 3-bis(hydroxyimino)-piperazine was obtained similarly through the addition reaction of cyanogen-di-N-oxide with N,N' -diphenyl-ethylenediamine. The square-planar complexes of vic-dioximes with various transition metal ions have been definitely determined. Two hydrogen bridges also adds to the stability of the molecule. In the case of some strained vic-dioximes, the ligand is unable to coordinate through both of the N atoms of the oximes as in the case of βcamphorquinonedioxime. Special features of the transition metal complexes of diaminoglyoxime derivatives attract attentions since Co(II) and Co(III) complexes of the parent compound have been reported. The anti and amphl isomers of vic-dioximes have been also studied since they form N,N or N,0 chelates according to the structure of the ligand. In the present work, we desribe the synthesis of a new five-membered heterocyclic vic-dioxime and its comp lexes with various transition metal ions. 1, 3-Disubstituted derivatives of imidazolidines are(essentially prepared (when a suitably N,N' -disubstituted jethylene diamine is Created with an aldehyde in an inert.solvent. The only reported vic-dioxime derivative of Amidazolidine, namelyj 1, 3-diphenyl 1-2-thioxo-4,5-bis (hydroxyimino)-imidazoline, could have been prepared.from diphenylthiourea with cyanogen-di-N-oxide. Although the rapid hydrolysis of the imidazolidines even in cold, dilute mineral acids jbrings special limitations, the synthesis of 1, 3-diphenyl-4,5-bis(hydroxyimino) -imidazo lidine (LH2) is accomplished under various conditions. Both anti-dichloroglyoxime and cyanogen-di-N-oxide is suitable for this reaction, but the highest yield is obtained when anti-djchloroglyoxime and N,N' -diphenyl- methylenediamine react at room temperature in ethanol with excess NaHCO3 as a buffer. In the 1H-n.m.r, spectrum of LH2, the chemical shift of OH protons appears as a broad single band at relatively low field(10.7 ppm) implying an anti-structure for the vic-dioximes. In the case of amphi-dioximes, the proton of the OH group which is directed towards the N-atom of the other hydroxyimino function participates in an intra molecular H-bonding(0-H...N), so two signals are observed for OH protons. Methylene protons have been also shifted to 6=5.3 ppm as a result of the cyclization. In the i.r. spectrum of LH2, (OH), (C=N) and (N-0) stretches are observed at 3180,1675 and 960 cm-1 respectively. Other than these characteristic vibrations, a broad band about 2800-2600 cm-1 and a narrow band at i 3340 cm-1 imply the presence of N-H and N+ -H groups. Similar i.r. spectra have been also obtained with 1, 3-diphenyl-2-thioxo-4,5-bis(hydroxyimino)-VI imidazoline and l,4-diphenyl 1-2, 3-bis(hydroxyimino)-piperazine. Consequently, the i.r. spectra can be interpereted as the formation of 0-H...N bridges between 0-H groups of oximes and N-atoms of the ring. The non-planar structure of the saturated ring enables this H-bridges. The mass spectrum of LH_ shows molecular ion peak at 282. Ni(II), Co(II), Cu(II), Pd(II), and U02(VI) complexes of LH2 have been isolated; in all these complexes metal/ligand ratio is 1:2. LH2 does not give characteristic red anti-dioxime complex with Ni(II). The pale-yellow color of (LH)2Ni indicates N,0 chelatation as seen in many amphi-dioximes. The strained imidazolidine ring probably prevents the formation of 5-membered NN-chelates with Ni(II). In the case of anti-camphorquinonedionedioxime(Hcqd), the failure to obtain Ni(II) complex has been explained as due to the strained camphor skeleton. The rigid bicyclic skeleton of of Hcqd is thus reponsible for larger N...N distance(3.0A°) Consequently, if the N-Ni-N angle is taken as 80° as in [Ni(dmg)2], the Ni-N distance is expected to be 2.3 A0 which is larger than that the value (1,85 A°) reported for [Ni(dmg)2]. (LH)2Ni complex has a magnetic moment of 3.14 B.M. so the complex is not planar as the various diamagnetic NN-chelated vic-dioximes. In (LH)2Ni, the tetrahedral distortion is accomplished by the 6-membered chelate ring. HO. // \\ V- / N- 0 N.N-X Ni The 1H-n.m.r. spectra of Ni(II) and Co(II), complexes of LH2, are heavily broadened due to the para magnetism, so the chemical shift values can not be strictly idenditified. In the brown Co(II) complex of LH2, the presence of a coordinated water molecule is shown by the broad absorption at 3250 cm-1 and the elemental analysis agrees with this composition. The magnetic moment of Co(LH)2. H2O at 19°C is 3.72 B.M. suggesting a square-pyramidal structure. As is the case for most anti-dioximes, LH2 forms square-planar complexes with Cu(II), Pd(II), and U02(VI). (LH)2Cu is paramagnetic(ueff=1.85) and (LH)2Pd is dia magnetic. In all these three complexes, C=N stretching vibrations are not very much effected from N-metal bond formations. The weak bands at 1760 cm-1 are due to(0-H.. 0)bridges. The characteristic V(0=U=0) vibrations are observed at 900 cm-1 in the i.r. spectrum of (LH)2UO2.In the 1H-n.m.r. spectra of (LH)2Pd and (LH)2U02 in CF3COOH, aromatic (6.8-6 ppm, m) and methylene (4.9 ppm, s) protons have been shifted to lower field. As a result of this work, it may be concluded that 1, 3-diphenyl-4,5-bis(hydroxyimino)-imidazolidine has a strained structure because of the f ive-membered ring. Therefore, a tetrahedral complex is obtained with nickel(II) instead of the usual square-planar vic-dioxime complexes. The therapeutical effects of the ligand should be also investigated since both imidazolidine and vicdioxime groups are hopeful from this point of view.