第六讲 六元杂环化合物的构建

This reaction is also known as the Skraup-Doebner-Von Miller quinoline synthesis, and is named after the Czech chemist Zdenko Hans Skraup (1850-1910), and the Germans (Doebner) (1850-1907) and (1848-1899). When the α,β-unsaturated carbonyl compound is prepared in situ from two carbonyl compounds (via an Aldol condensation), the reaction is known as the Beyer method for quinolines. The reaction is catalyzed by lewis acids such as tin tetrachloride and scandium(III) triflate and bronsted acids such as p-toluenesulfonic acid, perchloric acid, amberlite and iodine.
9. Friedlä nder synthesis
the chemical reaction of 2-aminobenzaldehydes with ketones to form quinoline derivatives.
This reaction has been catalyzed by trifluoroacetic acid, toluenesulfonic acid, iodine, and Lewis acids.
a chemical reaction involving the condensation of unsubstituted anilines (1) with βdiketones (2) to form substituted quinolines (4) after an acid-catalyzed ring closure of an intermediate Schiff base (3).
a chemical reaction whereby an o-acylaminoacetophenone is transformed into two different hydroxyquinolines (products A and B) using hydroxide ion.
8. Pfitzinger reaction
9. Direct Synthesis of Pyridine Derivatives
J. AM. CHEM. SOC. 2007, 129, 10096-10097
10. an alkyne 2 and a ten-fold excess of a nitrile 3 in the presence of a Co catalyst led to the pyridine 4.
A. Kumar, R. A. Maurya, Synlett, 2008, 883-885.
Highly Chemoselective Metal-Free Reduction of Tertiary Amides
J. AM. CHEM. SOC. 2008, 130, 18-19
2. Chichibabin (Pyridine) Synthesis
O E CHO CHO NH3
RCHO NH3
E
RCHO
1.Hantzsch Dihydropyridine (Pyridine) Synthesis
Hantzsch 1,4-dihydropyridine and polyhydroquinoline derivatives were synthesized in excellent yields in aqueous micelles. The reaction is catalyzed by PTSA and strongly accelerated by ultrasonic irradiation.
In this example, nitrobenzene serves as both the solvent and the oxidizing agent. The reaction, which otherwise has a reputation for being violent ("the Chemical Inquisition"), is typically conducted in the presence of ferrous sulfate. Arsenic acid may be used instead of nitrobenzene and the former is better since the reaction is less violent. Reaction mechanism
屠树江 徐州师范大学化学系
王香善 徐州师范大学化学系
Four-Component Domino Reaction Leading to Multifunctionalized Quinazolines
Bo Jiang, Shu-Jiang Tu, Parminder Kaur, Walter Wever, Guigen Li. J. AM. CHEM. SOC. 2009, 131, 11660–11661
4. Krö hnke Pyridine Synthesis
5. Guareschi-Thorpe Condensation
6. Bohlmann-Rahtz Pyridine Synthesis The Bohlmann-Rahtz Pyridine Synthesis allows the generation of substituted pyridines in two steps. Condensation of enamines with ethynylketones leads to an aminodiene intermediate that, after heat-induced E/Z isomerization, undergoes a cyclodehydration to yield 2,3,6-trisubstituted pyridines.
B）以硝基苯为原料 以硝基苯为原料合成喹啉类化合物通常需要将硝基还原为氨基。 Watanabe 等发现在铁络合物（KHFe(CO)4）作用下可以实现类似Friedlander 反应合成喹啉类化合物。在KOH 存在下，以邻硝基苯甲醛和羰基化合物（乙醛， 丙酮和苯乙酮）为原料合成喹啉类化合物，收率分别为33%，55%和17%。KOH 主要为羟醛缩合催化剂，以及与羰基铁反应生成高铁酸盐，而高铁酸盐在反应中 起到还原硝基和环化的作用。
3. Petrenko-Kritschenko Pyridine Synthesis
Formation of piperidones via cyclization of two moles of aldehyde and one mole each of acetonedicarboxylic ester and ammonia or a primary amine
J. Org. Chem. 2006, 71, 6592-6595
3. Doebner reaction
the chemical reaction of an aniline with an aldehyde and pyruvic acid to form quinoline-4-carboxylic acids .
6. Niementowski quinoline synthesis
the chemical reaction of anthranilic acids and ketones (or aldehydes) to form γhydroxyquinoline derivatives
7. Camps quinoline synthesis
Chem. Commun. 2006, 1313.
第二节. 喹啉的合成

Current Organic Chemistry, 2005, 9, 141-161
1. Skraup synthesis
chemical reaction used to synthesize quinolines. It is named after the Czech chemist Zdenko Hans Skraup (1850-1910). In the archetypal Skraup, aniline is heated with sulfuric acid, glycerol, and an oxidizing agent, like nitrobenzene to yield quinoline
Skraup合成喹啉的注意事项： 芳胺与不饱和羰基化合物发生的是Michael加成，而不是Schiff碱； PhNO2是脱氢氧化剂，其它如SnCl4、I2、FeCl3等均是可用的氧化剂； 适量加入HBO3可提高产率，但机理不明 ；
第一步反应十分激烈，操作要小心，加入FeSO4可改善反应状况；
M. C. Bagley, R. Lunn, X. Xiong, Tetrahedron Lett., 2002, 43, 8331-8334.
7. Ciamician-Dennstedt重排
8. 三组分合成
Shi, F.; Tu, S. J.; Fang, F.; Li, T. J. ArkiVoc 2005, part i, 137–142
4. Conrad-Limpach synthesis