Z. Abood
2010
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journal of kerbala university
Abstract
In this research new1,3-oxazepine derivatives[6-11] were prepared starting from new Schiff bases [4] and [5]. 5,5'-{[3-(Methoxycarbonyl)-4-oxocyclohexa-2,5dienylidene]methylene}bis(2-methoxybenzoate) [2] was prepared by reaction of 5,5'-[(3carboxy-4-oxocyclohexa-2,5-dienylidene)methylene]bis(2-hydroxybenzoic acid) [1] with dimethyl sulphate in presence of anhydrous sodium carbonate in dry acetone. The trihydrazide derivative [3] was obtained from treatment of triester derivative [2] with hydrazine monohydrate in absolute ethanol. Reaction of the trihydrazide derivative [3] with each Furfural and Salicyladehyde, respectively, in presence of glacial acetic acid as catalyst in absolute ethanol resulted the formation of new triimine derivatives [4] and [5], respectively. Treatment of the resulting imines [4] and [5] with each maleic anhydride, phthalic anhydride and 3-nitrophthalic anhydride, respectively, under cycloaddition reactions conditions produced new tri(1,3oxazepine) derivatives [6-8] and [9-11] respectively. These new imines and 1,3-oxazepine derivatives may be used as antibiotics. The structures of all prepared compounds were confirmed by C. H. N. elementary analysis and FT-IR spectra. :ةصلاخلا تايته ريضحت ثحبلا اذه يف نت 3،4 [ذيبذد يرببي يسكوا 6 33 [ذيبذد دريف ذيدااو ييه ] 3 ، ] 5 يضح، ] 5 ، 5' { 4 يرًانو ك ييسكاثره( 3 يسكهالكب ساسكوأ 5,5 ( نسيرلرثه]يبذيرلرٌرباد 5 او)يٌن ييسكاثره 5 يد عت ييه ] 5 ، 5' ( 4 يسكانو ك 3 سكهالكب ساسكوأ 5,5 يبذرلرٌرباد ( ن]يرلرثه 5 [يبو)ٌبلا اه يح ييسكووذره 3 ي يٌا ياب بك يه ] ذيبياوذرالا ييالاا لاايته ميلد ايصحلا نت .ف جلا ىاارسلأا يف ةر هلالا مابداصلا ًانو ك دادان رثولا 4 ةيله اه ييه ] اسلاا يالاا لااته 5 لا ييالاا لاايتولا يد عت ىا .لايل.ولا اً يثبلاا ييف ي يولا يبياوذب الا ه ] ذيبياوذب ا 4 ييه يك يه ] تايته مي.دأ لايل.ولا اً يثبلاا يف ذد سه ه اك يجلثلا [رلخلا اه ح دادان ،يلااالا ملد ،ذب ابذل سل سلاو اوافواعلا [ذيبذد يريوبلاا ييالاا 3 و ] 5 ةيجت ٌلا يٌروبلاا ةيله اه ىع .يلاايالا ميلد ] 3 و ] 5 ذيبوذاًا ،[يرل ولا ذيبوذاًا ييه يك يه ] ،[يييرل ثعلا 4 ييييالاا تايييته لاييي.دا ةيييرتلحلا ةف يييقلاا لاد يييعت حو يييف لايييحت ،يلاايييالا ميييلد ،[يييرل ثعلا ذيييبوذاًاو اب ً ( 4،3 [ذييبذد يرببي ييسكوأ 6 8 و ] 9 33 وااييست ذييو ٍذييه [ذييبذجلا يرببي ييسكولأاو يرييوبلاا تاييته ىا .يلااييالا مييلد ] .ةبارح اد ضوك بك ولا رود بركا ت لاصخف ( ص ٌالا بسً رلحت ةح سان [ ضحولا (C. H. N. .ءا وحلا لاحت ةافلأا ف رحأو Introduction: Pericyclic reaction is concerted processe pass-through a single cyclic transition state structure involving simultaneously breaking and formation of bonds (1) .The kinetic studies for pericyclic reactions showed that the rates of these reactions do not change with changing polarity of the solvent, so these reactions never take place via generation of intermediate (1,2) . The kinetic studies also showed that the rates of these reactions are neither increased in presence of free radicals initiators nor decreased in presence of retardants, so pericyclic reactions never take place via generation of free-radicals (1,2) . A pericyclic reaction includes changing in bonding relationship which occurs as continuous concerted reorganization of electrons, Furthermore the cyclic transition state must correspond to an arrangement of the participating orbitals that can maintain a bonding interaction between the reaction components throughout the course of the reaction (2,3) . 1,3Oxazepine is unsaturated seven-membered hetrocycle containing oxygen atom in position (1), nitrogen atom in position (3) in edition of five carbons Oxazepine derivatives showed various Journal of Kerbala University , Vol. 8 No.1 Scientific . 2010 455 biological activities such as antibacterial (4) and inhibitors for some enzymes action (5) . Some of oxazepine derivatives are used in another applied fields (6) . For a long time, the synthesis of 1,3and 1,4-oxazepine rings was based on two limited classical types of reactions, the first reaction is called Valence-bond isomerization which is carried out via irradiation of polyarylpyridine N-oxides. This irradiation results in ring expansion to 1,3-oxazepine in high yield and some deoxygenation to the parent amines (7) . The second reaction is called Enamines condensation which is carried out by reaction of Erythro 1,2-diphenyl-2phenylaminoethanol with dimethylacetylene dicarboxylate in methanol at room temperature to give a mixture of the Michael adduct and tetrahydro-1,4-oxazepin-7-one (8) . Recently, cycloaddition reaction, which is a type from a pericyclic reactions is used to synthesis of 1,3-oxazepine ring (9-12) . This type of reactions is not limited and gives various 1,3-oxazepine ring derivatives. The type of cycloaddition reaction that used to synthesis of 1,3-oxazepine ring was classified as (2+5) → 7 cycloaddition reaction in which two atoms of imine group as two-membered component was added to five-membered component such as maleic or phthalic anhydrides to give a seven-membered heterocycle (13,14) . Schiff base or imine compounds containing active (C=N-) group. Imines are prepared via acid-catalysed condensation reaction between aromatic aldehydes or ketones and primary amines (1518) . Mechanism of reaction was well known (19) . Due to the great flexibility and diverse structural aspects, a wide range of Schiff bases have been synthesized and their complexation behavior studied (20,21) . Furthermore Schiff bases are reported to show a variety of interesting biological actions, including antibacterial (22) , antifungal (23) , anti mouse hepatitis virus (MHV) (24) , inhibition of herpes simplex virus type 1 (HSV-1) and adenovirus type 5 (Ad 5) (25) , anticancer (26) , anti mosquito larvae (27) and herbicidal activities (28) . Also, Schiff bases are important intermediates for the synthesis of some bioactive compounds such as β-lactams (29) . The target of this research is synthesis of new structures containing more than one bioactive imine group and 1,3-oxazepine ring which probably have some biological activities. Experimental: General 1) The solvents and liquid reagents were purified when it was necessary; the solid materials were also dried under reduced pressure when it was necessary. 2) T.L.C were performed on pre-coated sheets with 0.25 mm layer of Silica Gel GF254 of Merck company, the detection was followed by oxidation with iodine or H2SO4 in ethanol (60%) followed by heating . 3) Evaporating of solvents by using Buchi vacuum rotary evaporator type 160. 4) Melting points (M.P.) were determined by Stuart melting point apparatus. 5) Elemental analysis measured on E.A.300, EuroVector, Italy, 2003-AL-albayt University (Jordan). 6) FT-IR spectra were recorded on FT-IR 8400S, Schimadzu-Spectrophotometer and using KBr discs-kerbala university. Preparation Methods Synthesis of Dimethyl 5,5'-{[3-(methoxycarbonyl)-4-oxocyclohexa-2,5dienylidene]methylene}bis(2-methoxybenzoate) [2] 5,5'-[(3-carboxy-4-oxocyclohexa-2,5-dienylidene)methylene]bis(2-hydroxy-benzoic acid) [1] (2.11g, 0.0050mole) was dissolved in (25mL) of dry acetone, then anhydrous sodium carbonate (0.53g, 0.0050mole) was added and the mixture was left with stirring at room temperature for 20min., then dimethyl sulphate (3.15g, 0.0250mole) was added and the mixture was refluxed with stirring at 50oC for 24hrs., the solvent was then removed by evaporation and the product was extracted from the mixture by addition a solution of saturated sodium Journal of Kerbala University , Vol. 8 No.1 Scientific . 2010 456 bicarbonate in distilled water and ethyl acetate (4×25mL). The organic layer was dried with anhydrous magnesium sulphate and removed by evaporation, recrystallized from ethanol, yield 82%, M.P.190-192oC. Synthesis of 5,5'-{[3-(hydrazinecarbonyl)-4-oxocyclohexa-2,5-dienylidene] methylene}bis(2-methoxybenzohydrazide) [3] Amixture of triester derivative [2] (2g, 0.0040mole) and hydrazine hydrate (0.60g, 0.0120mole) in absolute ethanol (20mL) was refluxed with stirring on water bath at 75oC for 6hrs. The hydrazide was precipitate on cooling, filtered off and recrystallized from ethanol,T.L.C. (ethanol:pet.ether) (1:3), Rf=0.59,yield 78%, M.P.185oC. Synthesis of 5,5'-{[3-(2-(furan-2-ylmethylene)hydrazinecarbonyl)-4-oxocyclohexa-2,5-dienylidene]methylene}bis[N-(furan-2-ylmethylene)-2-methoxybenzohydrazide] [4] Trihydrazide derivative [3] (0.984g, 0.002mole) was dissolved in absolute ethanol (15mL), then Furfural (0.576g, .006mole) containing two drop of glacial acetic acid was dissolved in absolute ethanol (15mL) and then added dropwise. The reaction mixture was refluxed with stirring on water bath at 70oC for 2hrs. Then the mixture was allowed to cool down to room temperature. The coloured precipitate was filtered and washed well with cold ethanol, T.L.C. (ethanol:pet.ether) (1:1), Rf=0.64, yield 77%, M.P. 246-248oC. Synthesis of 5,5'-{[3-(2-(2-hydroxybenzylidene)hydrazinecarbonyl)-4-oxocyclohexa-2,5-dienylidene]methylene}bis[N-(2-hydroxybenzylidene)-2-methoxybenzohydrazide] [5] Trihydrazide derivative [3] (0.984g, 0.002mole) was dissolved in absolute ethanol (15mL), then 2-Hydroxybenzaldehyde (0.732g, 0.006mole) containing two drop of glacial acetic acid was dissolved in absolute ethanol (10mL) and then added dropwise. The reaction mixture was refluxed with stirring on water bath at 70oC for 2hrs. Then the mixture was allowed to cool down to room temperature. The coloured precipitate was filtered and washed well with cold ethanol, T.L.C. (methanol:benzene) (1:2), Rf=0.69,yield 75%, M.P. 260-262oC. Synthesis of 5,5'-{[3-(2-(furan-2-yl)-4,7-dioxo-1,3-oxazepin-3(2H,4H,7H)-yl carbamoyl)-4-oxocyclohexa-2,5-dienylidene]methylene}bis{N-[2-(furan-2-yl)-4,7dioxo-1,3-oxazepin-3(2H,4H,7H)-yl]-2-methoxybenzamide} [6] Schiff base derivative [4] (0.363g, 0.0005mole) and Maleic anhydride (0.147g, 0.0015mole) were dissolved in (20mL) of dry benzene. The reaction mixture was refluxed with stirring on water bath at 75oC for 4hrs., The mixture was then allowed to cool down to room temperatue, the coloured p