11,12-dihidroksi-5,7-dimetilkumestan makrohalkalı eter türevinin sentezi ve yapısının aydınlatılması

Abstract

Bu çalışmada; o-dihidroksikumestan ve ayrıca yapısal benzerlik gösteren 6,7-dihidroksi-3,3-dimetil-3,4-dihidro-2H-dibenzofuran-1 -on bileşikleri sentezlenmiştir. Oluşan bu bileşiklerden, belirli katyon ve molekül ile kompleks oluşturma özelliğine sahip makrohalkalıpolieterler ve ayrıca siklik eterler sentezlenmiştir. Bu amaçla; hedeflenen makrohalkalıpolieterler ve siklik eterlerin sentezlenmesi için giriş maddeleri olan 11,12-dihidroksi-5,7-dimetilkumestan (I) ile 6,7-dihidroksi-3,3-dimetil-3,4-dihidro-2H-dibenzofuran-1-on (II) bileşiklerinin sentezlenmesi gereği ortaya çıkmıştır. Bu bileşiklerden 11,12- dihidroksi-5,7-dimetilkumestan oluşturmak için, giriş maddesi olan 5,7-dimetil- 4-hidroksikumarinin (VIII) sentezlenmesi de gerekmiştir. Dolayısıyla önce 5,7-dimetil-4-hidroksikumarin; 3,5-dimetilfenol ile malonikasidin POCI3, ZnCI2 ortamında 60-65 °C'de 35 saat süren siklizasyon reaksiyonu sonunda sentezlenmiştir. Oluşan 5,7-dimetil-4-hidroksikumarin ile katekolün sulu sodyumasetat ve potasyumiyodat ortamında `Wanzlick` kenetlenme reaksiyonu üzerinden 11,12-dihidroksi-5,7-dimetilkumestan, aynı şartlarda katekol ile 5,5-dimetilsiklohekzan-1,3-dion bileşiğinden kumestanla yapısal benzerlik gösteren 6,7-dihidroksi-3,3-dimetil-3,4-dihidro-2H-dibehzofuran-1 -on bileşikleri sentezlenmiş, oluşan bu bileşiklerden önce 1,2-dibromoetan ile sulu I K2C03 ve DMF ortamında 70-75 °C'de 35 saat SN2 mekanizması üzerinden 1 1,1 2-(etilendioksi)-5,7-dimetilkumestan (V) ve6,7-(etilendioksi)-3,3-dimetil-3,4- dihidro-dibenzofuran-1-on (III) siklik eterleri sentezlenmiştir. Aynı metodla trietilenglikolditosilat kullanılarak 11,12-dihidroksi-5,7-dimetilkumestan, ve

In this study, it was planned to prepare macroclylic polyether derivatives of vicinal dihydroxycoumestan and that of similar heterocyclic structure. Two of these compounds are 11,12-dihydroxy-5,7-dimethylcoumestan (I) and 6,7- dihydroxy-3,3-dimethyl-3,4-dihydro-2H-dibenzofurane-1-on (II). These compounds undergo reaction with polyethylenglycoldichloride or polyethylenglycolditosylate in the weak basic DMF/K2CO3/H2O solution affording macrocyclic polyether. 11,12-Dihydroxy-5,7-dimethylcoumestan (I) is of special interst in view of its vicinal phenolic groups, in addition to being a naturally occuring flavonoid. The other compound has also o- dihydroxyphenolic group. For the preparation of 11,12-dihydroxy-5,7- dimethylcoumestan (I) we first started with the synthesis of 5,7-dimethyl-4- hydroxy coumarine. Synthesis was performed by allowing 3,5- dimethylphenole to react with malonicacid in presence of POCI3, ZnCI2 at 60° for 35 hours. 11,12-dihydroxy-5,7-dimethyl coumestane (I) was prepared by the reaction of 5,7-dimethyl-4-hydroxycoumarine (VIII) and catechol in aqueous sodiumacetate/KI03 solution. Recrystallization of the crude product in ethylacetate gave pure required compound. 6,7-Dihydroxy-3,3-dimetyl- 3,4-dihydro-2H-dibenzofurane-1-one was synthesized similarly reacting 5,5- dimethylcyclohexane-1,3-dione with catechol inder the same condition described above. The synthetic strategy for the preparation of ethylendioxy (III, V), 12- Crown-4 (IV-VI) derivatives of 11,12-dihydroxy-5,7-dimethylcoumestan (I) and 6,7-dihydroxy-3,3-dimetyl-3,4-dihydro-2H-dibenzofurane-1-one is based on the substitution reaction with both 1,2-dibromo-ethane and triethyleneglycolditosylate respectively. 5,7-Dimethyl-11,12- dihydroxycoumestano-[15-Crown-5] (VII) was also prepared in the same way described. Above here we used tetraethylenegylicoldichloride instead of tetraethyleneglycolditosylate. These reactions were carried out in DMF and viiaqueous K2CO3 solution at 70-75° for 35 hours. The cooled solution was quenched by the addition of diluted acid and then the volatiles were evaporated at the rotary evaporatior. The residue was extraced with CHCI3 several times. The combined CHCI3 phases were washed with water. Evaporation of the combined organic phases gave the crude product which was purified by column chromatography on silica gel using CHCI3 as eluent. The structures of prepared compounds were determined by IR, 1H-NMR, 13C-NMR. In conclusion, our synthetic route is first applicable example in the synthesis of macrocylicpolyether derivatives of coumestan and related heterocyclic compounds. Consequently, we showed that the vicinal dihydroxycoumestane and some other similar heterocyclic vicinal dihydroxyphenols can be used to obtain their corresponding macrocyclic polyethers. VIII