Asiklik nitronların bazı dipolsevenlerle 1,3-dipolar halkakatılma reaksiyonlarının incelenmesi
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Date
2006-06-28
Authors
Öztürk, Aylin
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Publisher
Uludağ Üniversitesi
Abstract
Bazı Asiklik Nitronların DMAD ve N-Arilmaleimidlerle 1,3-DipolarHalkakatılma Reaksiyonlarının AraştırılmasıAsiklik nitronların DMAD ile reaksiyonu 2a,c,e olması durumunda kararlı 2,3-dihidroizoksazol-4,5-dikarboksilik asit dimetil esterlerini vermektedir. Fenil halkasının C-3karbonunda elektron salıcı grup taşıyan 4-izoksazolinler parçalanmaya uğrayarak fenilin C-3karbonuna bağlı olarak karşılık gelen aldehitleri ve birbirinden ayrılamayan içinde izokinolininbulunduğu tespit edilen ürün karışımını vermektedir. 2a izoksazolininin oda sıcaklığında metoksit ilereaksiyonu oldukça fonksiyonel 4-hidroksi-1-(metoksi-fenil-metil)-5-okso-2-fenil-2,5-dihidro-1H-pirol-3-karboksilik asit metil esterinin diastereoizomerik karışımını oluşturmaktadır. 2a-ebileşiklerinin propilamin ile regioselektif reaksiyonu izoksazolinlerden 2 daha kararlı olan 5-propilkarbamoil-2,3-dihidroizoksazol-4-karboksilik asit metil esterlerini 3a-e meydana getirmektedir.1a nitronu elektron salıcı sübstitüent taşıyan arilmaleimidler ile endo seçicilik gösterir ve anaürün olarak ekzo ürünü meydana getiren elektron çekici grup taşıyan maleimidlerden daha hızlıreaksiyon verir. N-Fenilmaleimid 13a olması durumunda herhangi bir seçicilik gözlenmez. 1a'nınZnBr2 kompleksinin 12a N-arilmaleimidlerle reaktivitesinin serbest nitrona göre ters olduğu veyöntemin ekzo seçicilikle ilerlediği kanıtlanmıştır. 4-Nitrofenilmaleimidlerin farklı sübstitüe nitronlarile reaksiyonları yüksek verimle karşılık gelen ekzo 2-benzil-3,5-difenil-dihidro-2H-pirol[3,4-d]izoksazol-4,6(5H,6aH)-dionları meydana getirmektedir. Dipolar halkakatılmaların ekzo-endoseçiciliğinin konsantrasyona bağlı olduğu kanıtlanmıştır. Düşük konsantrasyonlarda reaksiyon ekzoseçicilikle ilerlerken daha yüksek konsantrasyonlarda reaksiyonun seçiciliği ortadan kalkmıştır.Reaksiyon karışımına aromatik maddelerin ilave edilmesi reaktanların aromatik halkalarıyla stackingetkileşimi oluşturmaları nedeniyle halkakatılma reaksiyonlarının seçiciliğini ve hızını etkilemektedir.Endo ürün daha önce görülmemiş yapısal özellik göstermektedir. Kimyasal ve spektral kanıtlarhidrojenin bağlı olduğu beş üyeli heterohalka içinde kararlı bir diradikalin oluştuğunu kanıtlamaktadır.Halkakatılma ürünlerinin halkaaçılma reaksiyonları karşılık gelen nitronları oluşturmaktadır. Sekonderaminlerin bulunduğu ortamda halkaaçılma reaksiyonları beklenen amidleri meydana getirmiştir.Tersiyer aminler ise hiçbir şekilde etkili olmamıştır.
Search for the 1,3-Dipolar Cycloaddition Reactions of Acyclic Nitroneswith DMAD and N-ArylmaleimidesAcyclic nitrones 1 were reacted with DMAD to give stable 2,3-dihydroisoxazole-4,5-dicarboxylic acid dimethyl esters in the cases of 2a,c,e. The 4-isoxazolines having electron-donatinggroups on the phenyls at C-3 were shown to undergo unprecedented fragmentation to give thealdehyde corresponding to the phenyl at C-3 and an inseparable mixture containing isoquinoline. Thereaction of isoxazoline 2a with methoxide at room temperature afforded a diastereomeric mixture ofhighly functionalised 4-hydroxy-1-(methoxy-phenyl-methyl)-5-oxo-2-phenyl-2,5-dihydro-1H-pyrrole-3-carboxylic acid methyl ester. Regioselective reaction of compounds 2a-e with propylamine led tocorresponding 5-propylcarbamoyl-2,3-dihydroisoxazole-4-carboxylic acid methyl esters 3a-e whichwere more stable than the parent isoxazoles 2.Nitrone 1a reacts with arylmaleimides 13 having electron-donating substituents endoselectively and faster than with maleimides with electron-withdrawing groups where the mainproducts are the corresponding exo adducts. The process was unselective in the case of N-phenylmaleimide 13a. The reactivity of 1a ZnBr2 complex 12a with N-arylmaleimides was proved tobe reverse of the free nitrone and the process was shown to proceeds exo selectively. The reaction of4-nitrophenylmaleimide with a series of differently substituted nitrones 1a,b,e,i, led predominantly tothe formation of corresponding exo 2-benzyl-3,5-diphenyl-dihydro-2H-pyrrolo[3,4-d]isoxazole-4,6(5H,6aH)-diones in good yields. The exo-endo selectivity of the dipolar cycloaddition was provedto be concentration dependent process . At low concentrations the reaction is exo selective while athigher concentrations the process is unselective. Aromatic substances added to the reaction mixturesaffect rates and the selectivity of the cycloaddition reaction by stacking interactions with the aromaticrings of the reactants. The endo adducts show unprecedented structural features. The spectral andchemical evidences clearly revealed the formation of exclusively stable diradical where the hydrojen isinvolved in a five membered heterocycle. Retrocycloaddition of the cycloadduct produce thecorresponding nitrones. The ring-opening in the presence of secondary amines give expected amides.Tertiary amines did not induce any reaction.
Search for the 1,3-Dipolar Cycloaddition Reactions of Acyclic Nitroneswith DMAD and N-ArylmaleimidesAcyclic nitrones 1 were reacted with DMAD to give stable 2,3-dihydroisoxazole-4,5-dicarboxylic acid dimethyl esters in the cases of 2a,c,e. The 4-isoxazolines having electron-donatinggroups on the phenyls at C-3 were shown to undergo unprecedented fragmentation to give thealdehyde corresponding to the phenyl at C-3 and an inseparable mixture containing isoquinoline. Thereaction of isoxazoline 2a with methoxide at room temperature afforded a diastereomeric mixture ofhighly functionalised 4-hydroxy-1-(methoxy-phenyl-methyl)-5-oxo-2-phenyl-2,5-dihydro-1H-pyrrole-3-carboxylic acid methyl ester. Regioselective reaction of compounds 2a-e with propylamine led tocorresponding 5-propylcarbamoyl-2,3-dihydroisoxazole-4-carboxylic acid methyl esters 3a-e whichwere more stable than the parent isoxazoles 2.Nitrone 1a reacts with arylmaleimides 13 having electron-donating substituents endoselectively and faster than with maleimides with electron-withdrawing groups where the mainproducts are the corresponding exo adducts. The process was unselective in the case of N-phenylmaleimide 13a. The reactivity of 1a ZnBr2 complex 12a with N-arylmaleimides was proved tobe reverse of the free nitrone and the process was shown to proceeds exo selectively. The reaction of4-nitrophenylmaleimide with a series of differently substituted nitrones 1a,b,e,i, led predominantly tothe formation of corresponding exo 2-benzyl-3,5-diphenyl-dihydro-2H-pyrrolo[3,4-d]isoxazole-4,6(5H,6aH)-diones in good yields. The exo-endo selectivity of the dipolar cycloaddition was provedto be concentration dependent process . At low concentrations the reaction is exo selective while athigher concentrations the process is unselective. Aromatic substances added to the reaction mixturesaffect rates and the selectivity of the cycloaddition reaction by stacking interactions with the aromaticrings of the reactants. The endo adducts show unprecedented structural features. The spectral andchemical evidences clearly revealed the formation of exclusively stable diradical where the hydrojen isinvolved in a five membered heterocycle. Retrocycloaddition of the cycloadduct produce thecorresponding nitrones. The ring-opening in the presence of secondary amines give expected amides.Tertiary amines did not induce any reaction.
Description
Keywords
Dipolar halkakatılma, Asiklik nitronlar, 4-izoksazolinler, Pirol türevleri, 1H-pirol-3-karboksilik asit metil esteri, 2-arilpirolidin, DMAD, Seçici amidasyon, π-π stacking, Aromatik etkileşimler, Ekzo-endo seçicilik, Dipolar cycloaddition, Acyclic nitrones, 4-isoxazolines, Pyrrole derivative, 1Hpyrrole- 3-carboxylic acid methyl ester, 2-arylpyrrolidine, Selective amidation, π-π stacking, Aromatic interactions, Exo-endo selectivity
Citation
Öztürk, A. (2006). Asiklik nitronların bazı dipolsevenlerle 1,3-dipolar halkakatılma reaksiyonlarının incelenmesi. Yayınlanmamış yüksek lisans tezi. Uludağ Üniversitesi Fen Bilimleri Enstitüsü.