2,3 - BİS (hidroksiimino) -1,4,7,10 - tetraaza- (5,6) - (11,12) - dibenzo-siklododeka - 5,11 - dien sentezi ve komplekslerinin incelenmesi

Abstract

Geçiş metalleri ile oluşturdukları komplekslerin ilginç yapıları yanısıra, vic-dioksimler antitümör etkileri konusunda da incelenmektedirler. Daha önce sentezi yapılan bir seri vic-dioksim ligandları ile ilgili çalışmaların bir devamı olarak poliaza makrosiklik yapı üzerinde vic-dioksim grubu taşıyan yeni bir ligandın sentezi gerçekleştirilmiştir. Bu amaçla önce o-nitroklorobenzen ile 1,2-etandiaminin kondensasyonundan 1,2-bis(o-nitrofenilamino) etan hazırlanmış ve bu bileşiğin Pd-aktif karbon (%10) katalizörlüğünde hidrazin hidrat (% 100) ile indirgenmesinden 1,2-bis(o-aminofenilamino) etan elde edilmiştir. Bu diaminin -5°C da aşırı NaHC0 3 varlığında anti-dikloroglioksim ile reaksiyonundan 2,3-bis(hidroksiimino) - 1,4,7,10-tetraaza-(5,6)-(11,12) dibenzo-siklododeka-5,11-dien(LH4 ) elde edilmiştir. Anti-dikloroglioksim ile 1,2-bis(o-aminofenilamino) etan arasındaki reaksiyon da herhangi bir yönlendirici (template) etki söz konusu değildir. Reaksiyon ortamında bulunan aşırı NaHC0₃ oluşan HCl'i nötralize etmek içindir. Alkali metal iyonlarının N- donor ligandlar ile kompleks oluşturma eğilimi zayıf olduğundan, makrosiklik yapı oluşumunda Na+ iyonunun template etkisi beklenemez. Halka teşekkülü için fenil grublarının -NH₂ leri uygun biçimde yönlendirdikleri düşünülebilir. Elementel analiz sonuçları ve spektral veriler makrosiklik yapının oluştuğunu göstermektedir. 1,2-Bis(o-aminofenilamino) etan'ın ¹H-n.m.r. spektrumunda sekander ve primer amin protonlorına ait kimyasal koymalar 4,4 ve 3,5 ppm de görülmektedir. Siklizasyon reaksiyonundan sonra 3,5 ppm deki band kaybolmakta ve 7,5 ppm'de amidik-NH protonlarına ait yeni bir pik ortaya çıkmaktadır. 12,1 ppm deki geniş bir band anti-yapısındaki oksim protonlarına aittir. -NH ve -OH protonlorına ait kimyasal kaymaların D₂O ilavesinden sonra kaybolması bu grubların kesin olarak tanınmasını sağlar. LH₄ ‘ün aromatik ve metilen protonları 6,8-6,2 ve 3,3 ppm'de görülür. LH₄'un karakteristik i.r. bandları 3220 cm(-1) (OH), 1645 cm-(1) (C=N) ve 1015 cm-(1) (NO) de ortaya çıkmaktadır. Bu değerler daha önce diaminoglioksim türevleri için verilen değerlere uyum göstermektedir. Bu ligand da iki oksim grubuna ilaveten mokrosiklik halkada dört tane azot atomu mevcuttur. Bu grublar kısmen veya tamamen kompleks oluşumuna katılabilirler. Cu(II), Co(II), Ni(II), Pd(II) ve U0₂ (VI) ile LH₄ trinükleer kompleksler vermiştir. Bu komplekslerde herbir makrosiklik halka da bir metal iyonu tutulmuş, iki ligand molekülündeki dört aksim grubu üçüncü metal iyonu ile koordinasyona girmiştir. Bu komplekslerin çözünürlükleri az olduğundan ¹H-n.m.r. ölçümleri yapılamamış KBr tabletleri içerisinde alınan i.r. spektrumlarında 0-H ... O deformasyon bandları 1710-1700 cm(-1) gözlenmiştir. Daha yumuşak şartlarda LH₄ ‘ün mono-nukleer Pd(II) kompleksi de izole edilmiştir. DMSO-d₆ da yeterince çözündüğü için ¹H-n.m.r. spektrumu alınabilen bu kompleksin NH, CH₂ ve aromatik protonlara ait kimyasal koyma değerleri ligand da gözlenen değerlere çok yakındır. Daha düşük alana kayan OH piki aksim gruplarının metal iyonu ile koordinasyona girdiğini gösterir. LH₄' ün Zn(II) kompleksinde de metal/ligand oranı 1:1 dir. Bu kompleksde Zn(II), oksimlerden birinin N, diğerinin O atomu üzerinden koordinasyona girer. Tetrahedral yapı için diğer iki koordinasyonu bir klorür iyonu ile bir su molekülü tamamlar.

The transition metal complexes of polyazamacrocyclic ligands have been the subject matter of great interest. In most of the synthethical routes, the template effect of the transition metal ions are the precursers of the cyclization step. In the previous works, we have studied the structures of various transiton metal complexes of diaminoglyoxime. In bis(diominoglyoximato)cobalt(II) diaminoglyoxime, the cobolt atom has a square bipyramidal coordination with the four oxime nitrogens of two cheloting diaminoglyoxime molecules in the basis and amino nitrogens of adjacent complexes ot the apexes, thus forming sort of choins in the lottice. The X-ray structure onolysis of another cobalt complex, tris (diaminoglyoximato)cobolt(III) trichloride has shown that cobalt is octahedrolly coordinated by the bidentate ligands. The octahedral cobalt(III) diaminoglyoxime complexes prepared under SO₂ and NO otmospheres have been investigated by thermal decomposition. The amphi- and anti- stereoisomers and complexes of 1,4- dipheny 1-2, 3-bis(hydroxyimino)-piperazine and 1,3- dipheny 1-2-thioxo-4,5-bis(hydroxyimino)-imidazoline have been isolated and interconversion of anti- and amphi- complexes has been studied. Transition metal complexes of 5,6-dihydrocyclopent [f,g] acenophthylene-1,2-diondioxime, acenophthylene-diondioxime and some new substituted mono-and di-aminoglyoximes have been investigated. The effect of crown ether groups on the complex formation of N,N'-bis(4'benzo[15-crown-5]) diaminoglyoxime have been reported. The macrocyclic vic-dioximes with 2 aza- and 2,3,4, or 5 oxa-groups have been synthesized without any template effect and their complexes have been isolated. In the present work, 1,2-bis(o-nitrophenylamino) ethane has been prepared from o-nitrochlorbenzene and 1,2-ethanediamine. This nitro compound is reduced to the corresponding diamino derivative, 1,2-bis(o-amino-phenylamino)ethane by hydrazine hydrate (% 100) and Pd/active carbon (% 10). The synthesis of 2,3-bis (hydoxyimino)-l,4,7,10 -rtetraaza-(5,6)-(11,12)-dibenzocyclododeca-5,11-diene was realized by the reaction of anti- dichloroglyoxime and 1,2-bis(o-aminophenyamino)ethane in ethanol at -5°C. NaHC0₃ has been used in this reaction in order to neutralize HCl formed during the reaction. Trinuclear complexes of this dioxime with copper(II), nickel(II), cobalt(II), palladium(II), and uranyl(VI) have been isolated. Under mild conditions, mono- nuclear complexes are obtained with palladium(II) and zinc(II). The cyclization reaction between anti-dichloroglyoxime and 1,2-bis(o-aminophenylamino)ethane is essentially untemplated. Solid NaHC0₃ is used in order to neutralize HC1 formed during the reaction. The template effect of Na+ ion in the macrocyclization steps of many polyetheric compounds can not be expected in this case because of the low tendency of alkali metal ions to form complexes with N-donor ligands. For the cyclization step, the bulky phenyl groups should direct -NH₂ groups into the proper positions. The elemental analyses and the spectral data are consistent with the macrocyclic structure. In the ¹H-n.m.r. spectrum of 1,2-bis(o-aminophenyamino)ethone, there are two singlets at 4.4 ppm and 3.5 ppm for secondary and primary amine protons, respectively. After the cyclization reaction, the singlet at 3.5 ppm disappears and a new band at 7.5 ppm which can be assigned to NH protons in the neighborhood of oxime groups comes out. A broad bond at 12.1 ppm is assigned to hydroxy protons of LH₄. This single band for hydroxy protons at lower field is a strong evidence for the anti-form of dioxime group. These NH ond OH protons can be also identified very easily, because of the disappearence of the chemical shifts of both protons on D₂O exchange. The chemical shifts of the aromotic protons and of the methylene protons of LH₄ are in accordance with those of a similar macrocyclic compound, 2,3-bis(hydroxyimino)- 1,4-diaza-7, 10-dioxa-(5,6), (11,12)-dibenzo-cyclododeca-5,11-diene. In the i.r. spectrum of LH₄, (OH) stretching vib-rations are observed at 3220 cm(-1) as a brood absorption. (C=N) and (N-0) stretching vibrations are at 1645 and 1015 cm(-1), respectively; these values are in hormony with the previously reported diaminoglyoxime derivatives. Symmetric and asymmetric CH₂ stretching vibrations are at 2940-2880 cm(-1). This ligand has four nitrogen donor atoms in the macrocylic ring other than two oxime groups. Consequently, oll or some of these donor groups can participate into the complex formotion according to the reoction conditions. The transition metal complexes tetraazamacrocyclic compounds have been investigated exclusively. When all of the NH groups are secondary amines, ionic complexes are obtained. Deprotonation of the ligand might occur when amide protons participate into the complex formation as in the complexes of N,N'-bis(2'-pyridinecarboxamide)-l,2-benzene or N,N'-bis(2-pyridylmethyl)oxamide. LH₄ gives trinuclear complexes with Cu(II), Ni(II), Co(II), Pd(II), and U0₂ (VI). In these complexes one metal ion is trapped in each macrocyle and another metal ion has been coordinated through the N atoms of oxime groups of two ligand molecules. The law solubility of these complexes hindered ¹H-n.m.r. measurements. In the i.r. spectra of these complexes, weak (OH... O) deformation vibrations are observed around 1710-1700cm(-1). In the visible spectra of the complexes, onyl chargetransfer bands are obs Under mild conditions, mononuclear Pd(ll) complex of LH₄ has been isolated. This complex precipitates at room temperature without addition solubility in DMSO is sufficient for of a ¹H-n.m.r.measurements. in the ¹H-n.m.r. spectrum the chemical shifts corresponding to NH, CH₂ , and aromatic protons are observed at frequencies very near to those of the ligand. Only OH band has been shifted to lower field. This shift can be explained as the coordination of metal ion to N-atoms of oxime groups. The elemental analytical results also show the presence of one ligand molecule and two chloride ions for each metal ion. Consequently, a mononuclear complex with 1:1 metal/ligand ratio can be proposed as the copper(ll) complexes of some vic-dioximes. The Zn(ll) complex of LH₄ also has 1:1 metal/ligand ratio. In this complex, two of the four coordination sites of Zn(ll) are occupied by the N atom of one of the oxime groups and O atom of the other oxime group. A chloride ion and a water molecule have been also coordinated to metal ion. The i.r. spectra is consistent with this tetrahedral structure. The interesting property of 2,3-bis(hydroxyimino)- 1,4,7,10-tetraaza-(5,6)-(11,12)-dibenzocyclododeca-5,11-diene (LH₄) is that this ligand coordinates through both aza-groups of macrocycle and oxime groups. Hence, trinuclear complexes of various transition metal ions could have been isolated for the first time. The insolubility of these complexes in common solvents is the only disadvantage, since this deficiency causes difficulty in structure determination. In further researches, solubility of this type of complexes can be improved by odding crown ether groups to the mocrocyclic compouds.