2-鹵-N-取代苯甲醯胺及N-取代胼合成氮、氧雜環化合物的探討

EXPLORATION OF 2-HALOGENATED N-SUBSTITUTED BENZAMIDE AND N-SUBSTITUTED HYDRAZIDES FOR THE SYNTHESIS OF OXYGEN AND NITROGEN HETEROCYCLIC COMPOUNDS

柯帝(TRIMURTULU KOTIPALLI)

指導教授 ： 姚清發

國立臺灣師範大學/理學院/化學系/博士(2016年)

https://doi.org/10.6345/NTNU202204583

摘要

本論文主要可分為兩個章節，第一章可被細分為四個部分，A部分是回顧2-鹵代-N-取代基苯甲醯胺衍生物合成以及配位體促使金屬催化反應或無金屬催化反應等相關報導。B部分探討由簡單易取得的2-碘-N-取代基苯甲醯胺與吲哚衍生物合成出吲哚並[1,2-a]喹唑啉衍生物，反應過程由兩步驟構成，第一步利用2-碘苯甲醯胺衍生物經由烏耳曼反應進行吲哚芳香化反應，第二步則在鈀試劑的催化下進行分子內碳-氫醯胺化，此方法提供一個簡單便利的途徑合成出吲哚並[1,2-a]喹唑啉衍生物。C部分是藉由三氟化硼乙醚作為試劑進行一鍋化環擴張以及碳-碳鍵生成反應合成出10-吲哚基苯並[b,f]氮䓬之衍生物，並適用於多種不同取代基且產率也有不錯的表現。D部分介紹以銅試劑催化2-碘苯甲醯胺衍生物與
多種苯胺、烯丙基胺、肉桂胺等衍生物進行烏耳曼反應，接續分子內碳-氫醯胺化反應合成喹唑啉衍生物。
第二章細分為兩部分，A部分是回顧1,3,4-惡二唑衍生物及1,2,4-三唑衍生物合成的相關文獻報導。B部分介紹一種新穎的方法：利用聯氨前驅物、三氟甲磺酸酐以及2氟吡啶 /吡啶合成出 1,3,4-惡二唑衍生物、1,3,4-惡二唑啉衍生物以及1,2,4-三唑衍生物，我們設計出具位向選擇性開關的取代基/試劑去合成惡二唑啉衍生物(2氟吡啶作為反應物 )、惡二唑衍生物與三唑衍生物( 吡啶作為鹼添加物 )，另外2氟吡啶與 三氟甲磺酸酐開啟一新的活化模式合成出環戊-2,4-二烯衍生物，也就是類似Zincke反應中的 吡啶 環裂解 。

關鍵字

鈀催化 ； 碘化亞銅 ； 吲哚[1,2-a]喹唑啉酮 ； 三氟化硼催化 ； 10-吲哚苯並氮雜 ； 亞銅及銅的鹽類化合物 ； C-N 耦合, C-H 醯胺化 ； 三氟甲磺酸酐和2-氟吡啶/吡啶 ； 透過吡啶環分解進行SNAr反應 ； 自耦合 ； 1,3,4-惡二唑/1,3,4惡二唑啉和1,2,4三唑

並列摘要

The contents of this dissertation is divided into two parts (Part I, Part II). Part Ι is subdivided into four sections i.e. Section A, B, C, D. Section A, illustrates the overview on 2-halo N-substituted benzamide derivatives. this section also described the previous reports and a brief survey on ligand promoted metal or metal free catalyzed reactions for the construction of C-C, C-N, C-O, C-S, CSe, C-Te bond formation reactions by using N-substituted benzamide. Section B, describes the “synthesis of indolo[1,2-a]quinazolinone derivatives via C-N cross coupling reaction followed by C-H amidation by using metal catalysts such as Pd and Cu salts. Section C, deals with the one pot synthesis of 10-indolylbenzo[b,f]azepine derivatives via tandem ring expansion and C-C bond formation under open atmospheric reaction condition mediated BF3.OEt2. Section D, describes an efficient method for the “synthesis of 2,3-disubstitutedquinazolinone derivatives via Ullman coupling followed by intramolecular C-H amidation in the presence of copper catalyst.
Part II is divided into two parts i.e. Section A, B. Section A is about the overview of 1,3,4oxadiazole and 1,2,4-triazole derivatives, classification and synthetic methods. Further, this section also describes the literature survey for the synthesis of 2,5 diaryl or alkyl 1,3,4-oxadiazole and 1,2,4-triazoles. Section B, described a novel protocol for the synthesis of 1,3,4oxadiazoles/1,3,4-oxadiazolines and 1,2,4-triazole derivatives from hydrazide precursor using triflic anhydride and 2F-pyridine/pyridine.

並列關鍵字

Palladium catalysis ； Copper(Ι)iodide ； indolo[1,2-a]quinazolinone ； BF3.OEt2 mediated ； 10-indolylbenzo[b,f]azepine derivatives ； Copper(I) or copper (II) salts ； C-N coupling, C-H amidation ； Triflic anhydride and 2F-pyridine/pyridine ； SNAr reaction followed by pyridinum ring cleavage ； homo coupling ； 1,3,4-oxadiazoles/1,3,4-oxadiazolines and 1,2,4-triazole

參考文獻

I.A.10. References

1. (a) Blaskó, G.; Gula, D. J.; Shamma, M. J. Nat. Prod. 1982, 45, 105; (b)Laboratori Baldacci S. p. A. JP 59046268, 1984 [Chem. Abstr. 1984, 101,54922]. (c) Kato, Y.; Ebiike, H.; Achiwa, K.; Ashizawa, N.; Kurihara, T.; Kobayashi, F. Chem. Pharm. Bull. 1990, 38, 2060. (d) Kato, Y.; Takemoto, M.; Achiwa, K. Chem. Pharm. Bull. 1999, 47, 529. (e) Chang, Z. L.; Zhu, D. Y. In The Alkaloids; Brossi, A., Ed.; Academic Press: New York. 1978, 31, 29. (f) Laboratori Baldacci S. p. A. JP 59046268, Chem. Abstr., 1984, 101, 54922. (g) Chia, Y. C.; Chang, F. R.; Teng, C. M.; Wu, Y. C. J. Nat. Prod. 2000, 63, 1160. (h) Botero Cid, H. M.; Tr¨ankle, C.; Baumann, K.; Pick, R.; Mies-Klomfass, E.; Kostenis, E.; Mohr, K.; Holzgrabe, U. J. Med. Chem. 2000, 43, 2155. (i) Larsen, T. O.; Breinholt, J. J. Nat. Prod. 1999, 62,1182. (j) Lee, J. J.; Kim, H. S.; Lee, J. H.; Hong, Y. S.; Park, Y. J. PCT Int. Appl. WO 2000075124. (k) Glushkov, V. A.; Shklyaev, Y. V. Chem. Heterocycl. Compd. 2001,37, 663. (l) Pettit, G. R.; Meng, Y. H.; Herald, D. L.; Graham, K. A. N.; Pettit, R. K.; Doubek, D. L. J. Nat. Prod. 2003, 66, 1065. (m) Krane, B. D.; Shamma, M. J. Nat. Prod. 1982, 45, 377. (n) Coelho, F.; Veronese, D.; Lopes, E. C. S.; Rossi, R. C. Tetrahedron Lett. 2003, 44, 5731. (o) Heaney, H.; Shuhaibar, K. F. Synlett. 1995, 47. (p) Smist, M.; Kwiecien, H. Curr. Org. Synth. 2014, 11, 676. (q) Duncton, M. A. J. Minisci Reactions: Versatile CH−Functionalizations for Medicinal Chemists. MedChemComm. 2011, 2,1135. (q) Baser, K. H. C. Isolation and Identification of Anisaldehyde and Three Alkaloids from Leaves of Thalictrum minus var. microphyllum. J. Nat. Prod. 1982, 45, 704. (r) Slavík, J.; Slavíková, L. Alkaloids from Papaver setigerum DC. Collect. Czech. Chem. Commun. 1996, 61, 1047. (s) Bentley, K. W. β-Phenylethylamines and the Isoquinoline Alkaloids. Nat. Prod. Rep. 2006, 23, 444.

2. (a) Asensio, J. A.; Gomez-Romero, P. Fuel Cells. 2005, 5, 336. (b) Ishida, J.; Hattori, K.; Yamamoto, H.; Iwashita, A.; Miharab, K.; Matsuoka, N. Bioorg. Med. Chem. Lett. 2005, 15,4221. (c) Carey, J. S.; Laffan, D.; Thomson, C.; Williams, M. T. Org. Biomol.Chem. 2006, 4, 2337. (d) Queguiner, G.; Marsais, F.; Snieckus, V.; Epsztajn, J. Adv. Heterocycl. Chem. 1991,52, 187. (e) Quirk, J.; Thornton, M.; Kirkpatrick, P. Nat.Rev. Drug Discovery. 2003, 2, 769.

3. (a) Weltin, D.; Picard, V.; Aupeix, K.; Varin, M.; Oth, D.; Marchal, J.; Dufour, P.; Bischoff, P. Int. J. Immunopharmacol. 1995, 17,265. (b) Weltin, D.; Holl, V.; Hyun, J. W.; Dufour, P.; Marchal, J.; Bischoff, P. Int. J. Radiat. Biol. 1997, 72, 685. (c) Velik, J.; Baliharova, V.; Fink-Gremmels, J.; Bull, S.; Lamka, J.; Skalova, L. Res. Vet. Sci. 2004, 76, 95. (d) Kar, A. Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)in Medicinal Chemistry, New Age International (P) Ltd. New Delhi, India, 2005, ISBN: 81-224-1565-2. (e) Baggaley, K. H.; English, P. D.; Jennings, L. J. A.; Morgan, B.; Nunn, B.; Tyrrell, A. W. R. J. Med. Chem. 1985, 28, 1661. (f) Leeson, P. D.; Springthorpe, B. Nat. Rev. Drug Discovery 2007,6, 881.

4. (a). Xia, Y.; Yang, Z. Y.; Hour, M. J.; Kuo, S. C.; Xia, P.; Bastow, K. F.; Nakanishi, Y.; Nampoothiri, P.; Hackl, T.; Hamel, E.; Lee, K. H. Antitumor Agents. Part 204: Synthesis and Biological Evaluation of Substituted 2-Aryl Quinazolinones. Bioorg. Med. Chem. Lett. 2001, 11,1193. (b). Eur. Patent 000463, 2005. (c) Holl, V.; Coelho, D.; Weltin, D.; Dufour, P.; Bischoff, P. Anticancer Res. 2000, 20, 3233. (d). Lee, H. S.; Han, D. S.; Won, D. K. Korean J. Pharmacogn. 1990, 21,52. (e). Welch, W. M.; Ewing, F. E.; Huang, J.; Menniti, F. S.; Pagnozzi, M. J.; Kelly, K.; Seymour, P. A.; Guanowsky, V.; Guhan, S.; Guinn, M. R.; Critchett, D.; Lazzaro, J.; Ganong, A. H.; Devries, K. M.; Staigers, T. L.; Chenard, B. L. Bioorg. Med. Chem. Lett. 2001, 11, 177.