Key Compounds in Synthesis of Quinoline Derivatives: Synthesis of Bromo, Nitro and Methoxy Quinolines

Osman Çakmak; Salih Ökten

Derleme

Yıl 2021, Cilt: 2 Sayı: 1, 124 - 132, 29.01.2021

Osman Çakmak Salih Ökten

Öz

Destekleyen Kurum

TÜBİTAK TBAG

Proje Numarası

TÜBİTAK Proje no: 112T394 (Temel Bilimler Araştırma Grubu)

Teşekkür

Bu çalışmanın desteklenmesini sağlayan Tübitak'a teşekkür ederiz.

Kaynakça

Agarwal, A. K., Jenekhe, S. A. (1991). New conjugated polyanthrazolines containing thiophene moieties in the main chain, Macromolecules, 24, 6806.
Bergstrom, F. W. (1944). Heterocyclic Nitrogen Compounds. Part IIA. Hexacyclic Compounds: Pyridine, Quinoline, and Isoquinoline, Chem. Rev. 35, 77-277.
Boschelli, D. H., Wang, D. Y., Ye, F., et al. (2001). Synthesis and Src Kinase Inhibitory Activity of a Series of 4-Phenylamino-3-quinolinecarbonitriles, J. Med. Chem. 44, 822-833.
Butler, J. L., Gordon, M. (1975). A Reinvestigation of Known Bromination Reaction of Quinoline, J. Heterocyclic Chem. 12, 1015-1020.
Cheng, C. C., Yan, S. J. (1982). The Friedländer Synthesis of Quinolines. Org. React., 28, 37. Çakmak, O., Ökten, S. (2017). Regioselective bromination: Synthesis of brominated methoxyquinolines, Tetrahedron. 73(36), 5389-5396.
Çakmak, O., Ökten, S. Alımlı, D., et al. (2018). Activation of 6-bromoquinoline by nitration: synthesis of morpholinyl and piperazinyl quinolines. Arkivoc, iii, 362-374.
Çakmak, O., Ökten, S. Alımlı, D., et al. (2020). Novel Piperazine and Morpholine Substituted Quinolines: Selective Synthesis through Activation of 3,6,8-Tribromoquinoline, Characterization and Their Some Metabolic Enzymes Inhibition Potentials. J. Mol. Struc., 1220, 1286662.
Desai, P. K., Desai, P., Machhi, D. et al. (1996). Quinoline derivatives as antitubercular ⁄ antibacterial agents. Indian J. Chem. Sect. B, 35(B), 871.
Ekiz, M., Tutar, A., Ökten, S.et al. (2018). Synthesis, characterization, and SAR of arylated indenoquinoline‐based cholinesterase and carbonic anhydrase inhibitors. Archiv der Pharmazie, 351:9, e1800167.
Eisch, J. J. (1962). Aza-aromatic substitution I. The selective bromination of the quinoline nucleus. J. Org. Chem. 27, 1318-1323.
Kirsch, R., Kleim, J. P., Ries, G., et al. (1997). DE Patent NO: 19,613,591.
Kouznetsov, V. V., Méndez L. Y. V., Gómez C. M. M. (2005). Recent progress in the synthesis of quinolines. Curr. Org. Chem. , 9, 141-161.
Köprülü T. K, Ökten, S., Tekin, Ş. et al. (2019). Biological evaluation of some novel quinolines with different functional groups as anticancer agents. J Biochem Mol Toxicol. 33(3), e22260.
Kress, J. T., Costantino, S. M. (1973). Selective bromination in nitrobezen. a convenient synthesis of 3-bromoquinoline, 4-bromoisoquinoline, and 4-phenly-5-bromopyrimidine. J. Heterocyclic Chem. 10, 409-410.
Manske, R. H. F.; Kukla, M.(1953). The Skraup Synthesis of Quinolines. Org. React., 7, 59.
Muscia, G. C., Bollini, M., Carnevale, J. P. et al. (2006). Microwave-assisted Friedländer synthesis of quinolines derivatives as potential antiparasitic agents. Tetrahedron Lett. 47, 8811.
Jenekhe, S. A., Lu, L., Alam, M. M. (2001). New Conjugated Polymers with Donor−Acceptor Architectures: Synthesis and Photophysics of Carbazole−Quinoline and Phenothiazine−Quinoline Copolymers and Oligomers Exhibiting Large Intramolecular Charge Transfer. Macromolecules, 34, 7315.
Jones, G. (1977). In The Chemistry of Heterocyclic Compounds; Weissberger, A.; Taylor, E.C., Eds.; John Wiley and Sons: Chichester, 32, Part I, 93-318.
Jones, G. (1996). In Comprehensive Heterocyclic Chemistry; Katritzky, A. R., Rees, C. W., Scriven, E. E., Eds., Pergamon Press: Oxford, 5, 167.
Ökten, S., Çakmak, O., Erenler, R. et al. (2013). Simple and Convenient Preparation of Novel 6,8-disubstituted Quinoline Derivatives and Their Promising Anticancer Activities, Turk. J. Chem. 37(6), 896-908.
Ökten, S., Çakmak, O. (2015). Synthesis of Novel Cyano Quinoline Derivatives, Tetrahedron Letters 56(39), 5337–5340.
Ökten, S., Çakmak, O., Saddiqa, A. et al. (2016). Reinvestigation of bromination of 8-substituted quinolines and synthesis of novel phthalonitriles, Org. Commun. 9(4), 82-93.
Ökten, S., Çakmak, O., Tekin, Ş. (2017a). The SAR study of 6,8-disubstituted quinoline derivatives as anti cancer agents. Turk. J. Clin. Lab. 8(4), 152-159.
Ökten, S., Çakmak, O., Tekin, Ş. et al. (2017b). A SAR Study: Evaluation of bromo derivatives of 8-substituted quinolines as novel anticancer agents. Lett. Drug Des. Dis. 14 (12),1415-1424. Ökten, S., Ekiz, M., Tutar, A. et al. (2019). SAR Evaluation of Disubstituted Tacrine Analogues as Promising Cholinesterase and Carbonic Anhydrase Inhibitors. Indian J Pharm. Edu. Res. 53(2), 268-275.
Ökten, S., Aydın Ali, Koçyiğit, Ü. M. et al. (2020). Quinoline-based Promising Anticancer and Antibacterial Agents, and Some Metabolic Enzymes Inhibitors, Archiv der Pharmazie, 353(9), e2000086.
Solomon, V. R.; Lee, H. (2009). Chloroquine and its analogs: A new promise of an old drug for effective and safe cancer therapies. Eur. J. Pharmacol. 625, 220.
Reitsema, R. H. (1948). The Chemistry of 4-Hydroxyquinolines. Chem. Rev. 43, 47. Şahin, A., Çakmak, O., Demirtaş, İ., et al. (2008). Efficient and selective synthesis of quinolines. Tetrahedron, 64 (43), 10068-10074.
Wengryniuk, S. E., Weickgenannt, A., Reiher, C. et al. (2013). Regioselective Bromination of Fused Heterocyclic N-Oxides. Org. Lett. 15, 792- 795.
Zhang, N., Wu, B., Powell, D., et al. (2000). Synthesis and structure-activity relationships of 3-cyano-4-(phenoxyanilino)quinolines as MEK (MAPKK) inhibitors. Bioorg. Med. Chem. Lett, 10, 2825-2828.

Key Compounds in Synthesis of Quinoline Derivatives: Synthesis of Bromo, Nitro and Methoxy Quinolines

Yıl 2021, Cilt: 2 Sayı: 1, 124 - 132, 29.01.2021

Osman Çakmak Salih Ökten

Öz

Amaç: Bu çalışmada, araştırma grubumuz tarafından gerçekleştirilen kinolin çekirdek yapısının brom, metoksi ve nitro grupları ile aktif hale getirilerek, kinolin grubu bileşiklerin hazırlanması üzerine geliştirilen yeni metotlar ve farklı reaksiyon stratejileri rapor edilmektedir.
Gereç ve Yöntem: 1,2,3,4-tetrahidrokinolin bileşiği moleküler bromla etkileştirilerek ve akabinde DDQ ile aromatlaştırılarak bir seri bromo kinolinler hazırlandı. Kinolin bromürler, bakır destekli nükleofilik yer değiştirme reaksiyonları ile siyano ve metoksi kinolin türevlerine dönüştürüldü. Bir sonraki adımda, siyano ve metoksi kinolinler ve 8-sübstitüe (8-hidroksi, 8-metoksi ve 8-aminokinolinler) Br2 ile muamele edilerek bir seri ileri işlevsel kinolin bromürlere dönüştürüldü. Diğer taraftan, bromo ve metoksi kinolinlerin asidik şartlarda nitrolama reaksiyonları incelendi.
Bulgular: Tetrahidrokinolinin bromlanması ve aromatlaştırılması neticesinde mono, di ve tri bromürler elde edilmiştir. Metoksi ve siyano kinolinlerin ileri brominasyonu beklenildiği gibi C-3 konumunda meydana geldiği ayrıca metoksi kinolinlerin C-5 konumundan da brominasyonu gerçekleşebildiği rapor edilmiştir. 8-Sübstitüe kinolinlerin bromlanmasında ise 8-hidroksi ve 8-amino kinolinler C-5, C-7 konumlarında mono ve di bromürleri netice verirken 8-metoksi kinolin ise sadece 5-bromo-8-metoksikinoline dönüştüğü belirlenmiştir. Öte yandan, bromo ve metoksi kinolinlerin nitrolaması yeni bir işlevselliğin önünü açmıştır. Nitro gruplar hem aminokinolinler için öncü bileşikler hem de inaktif olan kinolin halkasına elektronca zengin grupların takılmasını sağlamaktadır.
Sonuç: Sentezlenen bromo kinolin ve tetrahidrokinolinlerin hem nükleofilik hem elektrofilik hem de kenetlenme reaksiyonlarında etkin anahtar bileşikler olduğu ve elde edilen yeni bileşikler de ileri bromlama ve nitrolama rekasiyonları ile işlevsellik kazandırılabilmektedir.

Anahtar Kelimeler

Bromoquinoline, Methoxyquinoline, Nitroquinolines, Bromination, ,2,3,4-Tetrahydroquinoline

Proje Numarası

TÜBİTAK Proje no: 112T394 (Temel Bilimler Araştırma Grubu)

Kaynakça

Agarwal, A. K., Jenekhe, S. A. (1991). New conjugated polyanthrazolines containing thiophene moieties in the main chain, Macromolecules, 24, 6806.
Bergstrom, F. W. (1944). Heterocyclic Nitrogen Compounds. Part IIA. Hexacyclic Compounds: Pyridine, Quinoline, and Isoquinoline, Chem. Rev. 35, 77-277.
Boschelli, D. H., Wang, D. Y., Ye, F., et al. (2001). Synthesis and Src Kinase Inhibitory Activity of a Series of 4-Phenylamino-3-quinolinecarbonitriles, J. Med. Chem. 44, 822-833.
Butler, J. L., Gordon, M. (1975). A Reinvestigation of Known Bromination Reaction of Quinoline, J. Heterocyclic Chem. 12, 1015-1020.
Cheng, C. C., Yan, S. J. (1982). The Friedländer Synthesis of Quinolines. Org. React., 28, 37. Çakmak, O., Ökten, S. (2017). Regioselective bromination: Synthesis of brominated methoxyquinolines, Tetrahedron. 73(36), 5389-5396.
Çakmak, O., Ökten, S. Alımlı, D., et al. (2018). Activation of 6-bromoquinoline by nitration: synthesis of morpholinyl and piperazinyl quinolines. Arkivoc, iii, 362-374.
Çakmak, O., Ökten, S. Alımlı, D., et al. (2020). Novel Piperazine and Morpholine Substituted Quinolines: Selective Synthesis through Activation of 3,6,8-Tribromoquinoline, Characterization and Their Some Metabolic Enzymes Inhibition Potentials. J. Mol. Struc., 1220, 1286662.
Desai, P. K., Desai, P., Machhi, D. et al. (1996). Quinoline derivatives as antitubercular ⁄ antibacterial agents. Indian J. Chem. Sect. B, 35(B), 871.
Ekiz, M., Tutar, A., Ökten, S.et al. (2018). Synthesis, characterization, and SAR of arylated indenoquinoline‐based cholinesterase and carbonic anhydrase inhibitors. Archiv der Pharmazie, 351:9, e1800167.
Eisch, J. J. (1962). Aza-aromatic substitution I. The selective bromination of the quinoline nucleus. J. Org. Chem. 27, 1318-1323.
Kirsch, R., Kleim, J. P., Ries, G., et al. (1997). DE Patent NO: 19,613,591.
Kouznetsov, V. V., Méndez L. Y. V., Gómez C. M. M. (2005). Recent progress in the synthesis of quinolines. Curr. Org. Chem. , 9, 141-161.
Köprülü T. K, Ökten, S., Tekin, Ş. et al. (2019). Biological evaluation of some novel quinolines with different functional groups as anticancer agents. J Biochem Mol Toxicol. 33(3), e22260.
Kress, J. T., Costantino, S. M. (1973). Selective bromination in nitrobezen. a convenient synthesis of 3-bromoquinoline, 4-bromoisoquinoline, and 4-phenly-5-bromopyrimidine. J. Heterocyclic Chem. 10, 409-410.
Manske, R. H. F.; Kukla, M.(1953). The Skraup Synthesis of Quinolines. Org. React., 7, 59.
Muscia, G. C., Bollini, M., Carnevale, J. P. et al. (2006). Microwave-assisted Friedländer synthesis of quinolines derivatives as potential antiparasitic agents. Tetrahedron Lett. 47, 8811.
Jenekhe, S. A., Lu, L., Alam, M. M. (2001). New Conjugated Polymers with Donor−Acceptor Architectures: Synthesis and Photophysics of Carbazole−Quinoline and Phenothiazine−Quinoline Copolymers and Oligomers Exhibiting Large Intramolecular Charge Transfer. Macromolecules, 34, 7315.
Jones, G. (1977). In The Chemistry of Heterocyclic Compounds; Weissberger, A.; Taylor, E.C., Eds.; John Wiley and Sons: Chichester, 32, Part I, 93-318.
Jones, G. (1996). In Comprehensive Heterocyclic Chemistry; Katritzky, A. R., Rees, C. W., Scriven, E. E., Eds., Pergamon Press: Oxford, 5, 167.
Ökten, S., Çakmak, O., Erenler, R. et al. (2013). Simple and Convenient Preparation of Novel 6,8-disubstituted Quinoline Derivatives and Their Promising Anticancer Activities, Turk. J. Chem. 37(6), 896-908.
Ökten, S., Çakmak, O. (2015). Synthesis of Novel Cyano Quinoline Derivatives, Tetrahedron Letters 56(39), 5337–5340.
Ökten, S., Çakmak, O., Saddiqa, A. et al. (2016). Reinvestigation of bromination of 8-substituted quinolines and synthesis of novel phthalonitriles, Org. Commun. 9(4), 82-93.
Ökten, S., Çakmak, O., Tekin, Ş. (2017a). The SAR study of 6,8-disubstituted quinoline derivatives as anti cancer agents. Turk. J. Clin. Lab. 8(4), 152-159.
Ökten, S., Çakmak, O., Tekin, Ş. et al. (2017b). A SAR Study: Evaluation of bromo derivatives of 8-substituted quinolines as novel anticancer agents. Lett. Drug Des. Dis. 14 (12),1415-1424. Ökten, S., Ekiz, M., Tutar, A. et al. (2019). SAR Evaluation of Disubstituted Tacrine Analogues as Promising Cholinesterase and Carbonic Anhydrase Inhibitors. Indian J Pharm. Edu. Res. 53(2), 268-275.
Ökten, S., Aydın Ali, Koçyiğit, Ü. M. et al. (2020). Quinoline-based Promising Anticancer and Antibacterial Agents, and Some Metabolic Enzymes Inhibitors, Archiv der Pharmazie, 353(9), e2000086.
Solomon, V. R.; Lee, H. (2009). Chloroquine and its analogs: A new promise of an old drug for effective and safe cancer therapies. Eur. J. Pharmacol. 625, 220.
Reitsema, R. H. (1948). The Chemistry of 4-Hydroxyquinolines. Chem. Rev. 43, 47. Şahin, A., Çakmak, O., Demirtaş, İ., et al. (2008). Efficient and selective synthesis of quinolines. Tetrahedron, 64 (43), 10068-10074.
Wengryniuk, S. E., Weickgenannt, A., Reiher, C. et al. (2013). Regioselective Bromination of Fused Heterocyclic N-Oxides. Org. Lett. 15, 792- 795.
Zhang, N., Wu, B., Powell, D., et al. (2000). Synthesis and structure-activity relationships of 3-cyano-4-(phenoxyanilino)quinolines as MEK (MAPKK) inhibitors. Bioorg. Med. Chem. Lett, 10, 2825-2828.

Toplam 29 adet kaynakça vardır.

Ayrıntılar

Birincil Dil	Türkçe
Bölüm	Makaleler
Yazarlar	Osman Çakmak Salih Ökten 0000-0001-9656-1803
Proje Numarası	TÜBİTAK Proje no: 112T394 (Temel Bilimler Araştırma Grubu)
Yayımlanma Tarihi	29 Ocak 2021
Gönderilme Tarihi	24 Kasım 2020
Kabul Tarihi	18 Ocak 2021
Yayımlandığı Sayı	Yıl 2021 Cilt: 2 Sayı: 1

Kaynak Göster

APA	Çakmak, O., & Ökten, S. (2021). Key Compounds in Synthesis of Quinoline Derivatives: Synthesis of Bromo, Nitro and Methoxy Quinolines. Turkish Journal of Science and Health, 2(1), 124-132.