Naftofuran ve naftodioksosin türevlerinin sentezi

Abstract

Bu çalışmada glioksal ve glutardialdehit ' in 2-naf- tol, 2-tiyonaf tol, 2, 7-dihidroksinaf talin, 2, 3-dihidroksi naftalin, 2, 6-dihidroksinaf talin, 1, 5-dihidroksinaf talin ve l-hidroksi-5-metoksinaf talin ile asitli ortamda konden- sasyonu incelenmiştir. Glioksal' in 2-naftol, 2-tiyonaf tol, 2, 7-dihidroksi naftalin, 2,3-dihidroksinaf talin ve l-hidroksi-5-metoksi naftalin ile tepkimesi sonucunda sırasıyla, 7a,14c-dihid- ronaf tofuro [2,l-b]naf t of uran, 7a, 14c-dihidronaf totiyofeno [2, l-b]naf totiyofen, 2, 13-dihidroksi-7a, l4c-dihidronaf to furo [2, 1-b] naf tofuran, 6, 9-dihidroksi-7a, 14c-dihidronaf- tofuro [2, 1-b] naf tofuran ve 4,9-dimetoksi-6b,13a-dihidro naf tofuro [l,2-b] naf tofuran ele geçmiştir. Glutardialdehit ise 2-naftol, 2-tiyonaftol ve 1-hidroksi-5-metoksinaf talin ile tepkimesi sonucunda 8,16-pro- pano-16H-dinafto[2,l-d,g] [l, 3] dioksosin, 8, 16-propano- 16H-dinaf to[2,l-d,g] [1,3Jditiyosin ve 4, 10-dimetoksi-7, 15- propano-7H-dinafto [l,2-d,g] [1, 3] dioksosin bileşiklerini oluşturmuştur. 2,6-Dihidroksinaftalin ve 1, 5-dihidroksinaf talin ile gerçekleştirilen tepkimelerde hem glioksal hem de glu- tardialdehitle beklenen dimerik ürün yerine polimer ele geçmiştir. Yalnız glutardialdehit glioksal 'den farklı o- larak 2, 7-dihidroksinaf talin ile de polimer oluşturmuştur. Ayrıca elde edilen hidroksinaf tofuran bileşikleri üzerinde de tepkimeler gerçekleştirilerek bunların mono ve dimetoksi, asetoksi ile benzoksi türevleri elde edilmiştir. Ürünlerin yapılarının incelenmesinde FTIR, NMR ve kütle spektroskopisi yöntemleri kullanılmıştır. Polimerlerin tanımlanmasında ise viskozite ölçümlerinden yararlanılmıştır.

Naphthopyranonaphthopyran derivatives were synthe sized via the condensation reaction between dimethylol ketones and 2-naphthol in our laboratories previously. OH I CH9 R-C C-CH- i II CH, 0 I l OH + OH f-f -> Similar condensation reaction was carried out by 1,3-dihydroxyacetone with 2-naphthol and it was observed that the product was formed via methyl glyoxal and 2-naphthol- It was suggested that 1, 3-dihydroxyacetone first transformed to methyl glyoxal in acidic media and then reacted with naphthol. HO-CH-C-CH-OH 2 II 2 " 0 \K ?»CH-C-C-H 3 II II 0 0 OH VI In this work, the reaction of dicarbonyl compounds such as glyoxal (ethanedial) and glutardialdehyde (1,5- pentandial) with 2-naphthol, 2-thionaphthol, 2,7-dihydroxy naphthalene, 2, 6-dihydroxynaphthalene, 2,3-dihydroxynaph- thalene, 1, 5-dihydroxynaphthalene and l-hydroxy-5-methoxy naphthalene in acidic media were studied and the resulting products were characterized with FTIR, İH-NMR and mass spectra. In the table. 1, the reaction conditions, yields and structures of products were summerized. Table 1 : The reaction products of dicarbonyl compounds with naphthols. Reaction temperature : 50-60°C Reaction time: 4 h Dicarbonyl Compound Naphthol Compound Structure CHO I CHO OH (I) CHO I CHO SH S^S' (II) CHO I CHO HO OH (III) Vll Dicarbonyl Compound Naphthol Compound Structure CHO I CHO OH OH (IV) CHO I CHO OH CH30 OCH, (V) CHO I CHO HO OH Polymeric product (VI) CHO I CHO OH HO Polymeric product (VII) CHO (CH2)3 CHO OH (VIII) vxii Dicarbonyl Compound Naphthol Compound Structure CHO I (CH2)3 CHO SH (IX) CHO (CH2)3 CHO ch3o OCH, (X) CHO I (CH2)3 CHO HO OH Polymeric product (XI) CHO (CH2)3 I CHO HO OH Polymeric product (XII) CHO I (CH2}3 I 2 3 CHO Polymeric product (XIII) 7 a, 14c-Dihydronaphthof uro [2, 1-b] naphthof uran ( I ) was synthesized by the reaction with glyoxal and 2-naphthol, The product was a mixture of two isomers and these were observed in the.'-H-NMR spectrum. IX (A) (A) isomer has acetal structure and showed two dublets at 5.5 ppm (J=5.9 Hz) and 7.1 ppm (J=6.1 Hz) due to the protons H14c and H7a respectively. But (B) isomer has ether structure and two identical protons (H7a and H14a) because of the symmetry. These protons showed a singlet peak at 5 ppm. The existance of two isomers was not observed in other reactions and only acetal type products were recov ered. In the case of using 2-thionaphthol, the sulphur derivative of this structure was- not produced, but 2-(2- thionaphthalene) [2,l-b]naphthothiophene (II) was obtained. Similarly, 2, 13-dihydroxy-7a, 14c-dihydronaphthof uro [2,l-b]naphthofuran (III), 6,9-dihydroxy-7a,14c-dihydro naphthofuro[2,l-b]naphthofuran (IV) and 4,9-dimethoxy- 6b,13a-dihydronaphthofuro [1,2-b]naphthofuran (V) were syn thesized by the reactions of glyoxal with 2,7-dihydroxy naphthalene, 2, 3-dihydroxynaphthalene and 1 -hydroxyz ine thoxynaphthalene respectively. However, in the case of using 2,6-dihydroxynaphtha- lene and 1,5-dihydroxynaphthalene, dimeric products could not be obtained, instead only polymeric products were formed. Although, these reactions were repeated under the same conditions except naphthol/glyoxal mol ratio was increased 2 to 6, the same polymer formation could not be prevented. The structures of polymers were elucidated by using FTIR, ?LH-NMR spectra and solution viscosity. FTIR spectra showed that the hydroxyl content of the polymers were much higher than the chain end hydroxyls. Furhermore the same result was observed in İH-NMR spectra by calculating the ratio of hydroxyl protons to H14c proton of the acetal structure. From these results, the structure of polymers were proposed as follows. x Glutardialdehyde was also reacted with naphthols. Dimeric products such as 8, 16-propano-16H-dinaphtho [2,l-d,g]j 1,3] dioxocin (VIII), 8, 16-propano-16H-dinaphtho [2, 1-d, g] 1,3] dithiocin (IX) and 4, 10-dimethoxy-7, 15-propano-7H- dinaphtho [1,2-d,g] [l,3] dioxocin (X) were produced from the reactions of glutardialdehyde with 2-naphthol, 2-thio- naphthol and l-hydroxy-5-methoxynaphthalene respectively. Polymeric products (XII and XIII) were obtained by using 2, 6-dihydroxynaphthalene and 1, 5-dihydroxynaphtha- lenes. However in the case of using 2, 7-dihydroxynaphtha- lene, dimeric product could not be obtained, instead only polymeric product (XI) was isolated. The difference between the products of glyoxal and glutardialdehyde with 2, 7-dihydroxynaphthalene was explain ed by the structures of furofuran and dioxocin rings. In furofuran ring which formed by glyoxal, the hydroxyl groups of the compound were in 2 and 13 positions of the naphthofuran structure and close to each other. But in the dioxocin ring which formed by the corresponding dial- dehyde, the hydroxyl groups were in 2 and 14 positions of the structure so that any steric hindrance was elimi nated for polymerization. The polymers containing free hydroxyls were produced as in the case of using glyoxal and the structure of poly mers was proposed as follows. -> n XI Naphthofuronaphthofuran ring is known to have some anti-cancer and anti-AIDS properties, so that some reac tions such as methylation, acetylation and benzoylation were carried out with resulting hydroxy naphthofuran com pounds. In the following table, the reaction reagents and structures of the products were listed. Table 2 : The functional derivatives of hydroxynaphtho furan compounds. Naphthofuran Compound Substitution Reagent Structure och. III (CH3)2S04 CH30 OCH- (XIV) III CHrC-Cl 3 II 0 (XV) xi 1 Naphthofuran Compound Substitution Reagent Structure III <0^-c« II o (XVI) IV CKrC-Cl 3 II 0 CH3-C-O 3 II 0 0-C-CH3,11 0 (XVII) IV <0^ c-ci II 0 (XVIII) As can be seen in the table 2, only the mono deri vatives could be obtained from 2,13-dihydroxy-7a, 14c-di- hydronaphthofuro [2, 1-b] naphthofuran (III) and di deriva tives were obtained from 6,9-dihydroxy-7a,l4c~dihydronaph- thofuro[2, 1-bj naphthofuran (IV). The difference b di derivatives was prob hydroxyl groups of the 2 and 13 positions were the second was prevente tion reactions. Howeve methoxy derivative was may be considered due t etween the ably due to compounds. sterically d as in ace r in the ca obtained wi o smaller s formation of mono and the location of the It was suggested that close enough so that tylation and benzoyla- se of methylation, di- th low yield. This ize of methoxy groups.