Friedländer喹啉合成反应

此反应是指邻胺基芳基醛或酮与另一分子有α-亚甲基的酮反应得到喹啉的反应。反应中两个底物先缩合，得到的中间体经过酸或碱催化环脱水得到喹啉。

---

反应机理：

最新文献

Rapid and efficient synthesis of poly-substituted quinolines assisted by p-toluene sulphonic acid under solvent-free conditions: comparative study of microwave irradiation versus conventional heating
C.-S. Jia, Z. Zhang, S.-J. Tu, G.-W. Wang, Org. Biomol. Chem., 2006, 4, 104-110.

Molecular iodine: a highly efficient catalyst in the synthesis of quinolines via Friedländer annulation
J. Wu, H.-G. Xia, K. Gao, Org. Biomol. Chem., 2006, 4, 126-129.

Transition-Metal-Free Indirect Friedländer Synthesis of Quinolines from Alcohols
R. Martínez, D. J. Ramón, M. Yus, J. Org. Chem., 2008, 73, 9778-9780.

Silver Phosphotungstate: A Novel and Recyclable Heteropoly Acid for Friedländer Quinoline Synthesis
J. S. Yadav, B. V. S. Reddy, P. Sreedhar, R. S. Rao, K. Nagaiah, Synthesis, 2004, 2381-2385.

Efficient and Rapid Friedlander Synthesis of Functionalized Quinolines Catalyzed by Neodymium(III) Nitrate Hexahydrate
R. Varala, R. Enugala, S. R. Adapa, Synthesis, 2006, 3825-3830.

Ionic Liquid-Promoted Regiospecific Friedlander Annulation: Novel Synthesis of Quinolines and Fused Polycyclic Quinolines
S. S. Palimkar, S. A. Siddiqui, T. Daniel, R. J. Lahoti, K. V. Srinivasan, J. Org. Chem., 2003, 68, 9371-9378.

Synthesis of Quinolines via Friedländer Reaction in Water and under Catalyst-Free Conditions
Q. Shen, L. Wang, J. Yu, M. Liu, J. Qiu, L. Fang, F. Guo, J. Tang, Synthesis, 2012, 44, 389-392.

One-Pot Friedländer Quinoline Synthesis: Scope and Limitations
A.-H. Li, D. J. Beard, H. Coate, A. Honda, M. Kadablbajoo, A. Kleinberg, R. Laufer, K. M. Mulvihill, A. Nigro, P. Rastogi, M. W. Siu, A. G. Steinig, T. Wang, D. Werner, A. P. Crew, M. J. Mulvihill,Synthesis, 2010, 1629-1632.

Highly Regioselective Friedländer Annulations with Unmodified Ketones Employing Novel Amine Catalysts: Syntheses of 2-Substituted Quinolines, 1,8-Naphthyridines, and Related Heterocycles
P. G. Dormer, K. K. Eng, R. N. Farr, G. H. Humphrey, J. C. McWilliams, P. J. Reider, J. W. Sager, R. P. Volante, J. Org. Chem., 2003, 68, 467-477.

Solvent-Free Enantioselective Friedländer Condensation with Wet 1,1′-Binaphthalene-2,2′-diamine-Derived Prolinamides as Organocatalysts
A. Bañón-Caballero, G. Guillena, C. Nájera, J. Org. Chem., 2013, 78, 5349-5356.

编译自：有机化学门户

---

---

---

---

邻氨基芳基醛或酮与另一分子至少含有一个与羰基相连的亚甲基的醛或酮反应得到取代喹啉的反应。此反应可以通过加入酸，碱或加热加速反应。

反应机理：

首先两个分子先发生羟醛缩合，脱水得到α，β-不饱和醛酮，氨基再与羰基进行缩合得到喹啉。

反应实例：

参考文献：

1. Friedländer, P. Ber. Dtsch. Chem. Ges. 1882, 15, 2572. Paul Friedländer

(1857􀀐1923), born in Königsberg, Prussia, apprenticed under Carl Graebe and Adolf

von Baeyer. He was interested in music and was an accomplished pianist.

2. Elderfield, R. C. In Heterocyclic Compounds, Elderfield, R. C., ed.; Wiley & Sons,:

New York, 1952, 4, Quinoline, Isoquinoline and Their Benzo Derivatives, 45–47.

(Review).

3. Jones, G. in Heterocyclic Compounds, Quinolines, vol. 32, 1977; Wiley & Sons: New

York, 181–191. (Review).

4. Cheng, C.-C.; Yan, S.-J. Org. React. 1982, 28, 37. (Review).

5. Shiozawa, A.; Ichikawa, Y.-I.; Komuro, C.; Kurashige, S.; Miyazaki, H.; Yamanaka,

H.; Sakamoto, T. Chem. Pharm. Bull. 1984, 32, 2522.

6. Thummel, R. P. Synlett 1992, 1.

7. Riesgo, E. C.; Jin, X.; Thummel, R. P. J. Org. Chem. 1996, 61, 3017.

8. Mori, T.; Imafuku, K.; Piao, M.-Z.; Fujimori, K. J. Heterocycl. Chem. 1996, 33, 841.

9. Ubeda, J. I.; Villacampa, M.; Avendaño, C. Synthesis 1998, 1176.

10. Bu, X.; Deady, L. W. Synth. Commun. 1999, 29, 4223.

11. Strekowski, L.; Czarny, A.; Lee, H. J. Fluorine Chem. 2000, 104, 281.

12. Chen, J.; Deady, L. W.; Desneves, J.; Kaye, A. J.; Finlay, G. J.; Baguley, B. C.;

Denny, W. A. Bioorg. Med. Chem. 2000, 8, 2461.

13. Gladiali, S.; Chelucci, G.; Mudadu, M. S.; Gastaut, M.-A.; Thummel, R. P. J. Org.

Chem. 2001, 66, 400.

14. Hsiao, Y.; Rivera, N. R.; Yasuda, N.; Hughes, D. L.; Reider, P. J. Org. Lett. 2001, 3,

1101; and 2002, 4, 1243.

15. Henegar, K. E.; Baughman, T. A. J. Heterocycl. Chem. 2003, 40, 601.

16. Dormer, P. G.; Eng, K. K.; Farr, R. N.; Humphrey, G. R.; McWilliams, J. C.; Reider,

P. J.; Sager, J. W.; Volante, R. P. J. Org. Chem. 2003, 68, 467.

17. Pflum, D. A. Friedländer Quinoline Synthesis In Name Reactions in Heterocyclic

Chemistry, Li, J. J.; Corey, E. J., Eds.; Wiley & Sons: Hoboken, NJ, 2005, 411􀀐415.

编译自：Name Reactions （A Collection of Detailed Reaction Mechanisms）, Jie Jack Li, Friedländer quinoline synthesis，page 243-244.