Cohn quinoline synthesis

Conversion of acylanilides into 2-chloro-3-substituted quinolines by the action of Vilsmeier s reagent in warmed phosphorus oxychloride (POCI3) as solvent. 

Meth-Cohn, O. Narine, B. Tamowski, B. Tetrahedron Lett. 1979, 3111. 

Meth-Cohn, O Rhouati, S. Tamowski, B. Robinson, A. J. Chem. Soc., Perkin Trans. 1 1981, 1537. 

Meth-Cohn, O. Tarnowski, B. Adv. Heterocycl. Chem. 1982, 31, 207. (Review). 

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When iV-substituted acylanilides 9 are treated under the same reaction conditions, the corresponding lV-substituted-2-quinolones 10 are isolated in high yields. This reaction was initially misinterpreted, but it has since been demonstrated to follow a similar mechanistic pathway to the Meth-Cohn quinoline synthesis. ... 

In the Meth-Cohn quinoline synthesis, the acetanilide becomes a nucleophile and provides the framework of the quinoline (nitrogen and the 2,3-carbons) and the 4-carbon is derived from the Vilsmeier reagent. The reaction mechanism involves the initial conversion of an acylanilide 1 into an a-iminochloride 11 by the action of POCI3. The a-chloroenamine tautomer 12 is subsequently C-formylated by the Vilsmeier reagent 13 derived from POCI3 and DMF. In examples where acetanilides 1 (r = H) are employed, a second C-formylation of 14 occurs to afford 15 subsequent cyclisation and... 

In a useful extension to the Meth-Cohn quinoline synthesis, pyridoquinolin-2-ones 27 are readily prepared in a one-pot procedure by sequential treatment of an acetanilide 3, firstly with the Vilsmeier reagent from DMF and POCI3 to afford the intermediate 16, which is then further reacted in situ with another secondary amide. ... 

Similarly, W-methyl-D-aspartate (NMDA) antagonists 32 with analgesic activity were prepared, again using the Meth-Cohn quinoline synthesis as the key entry reaction, subsequent functional group manipulation giving the desired target compound. 

Moore, A. J. Meth-Cohn quinoline synthesis In Name Reactions in Heterocycl. Chemistry, Li, J. J. Corey, E. J., Eds. Wiley Sons Hoboken, NJ, 2005, 443—450. (Review). 

The application of Vilsmeier s reagent in acylanilides to produce 2-chloro-3-substituted quinolines is known as the Meth-Cohn quinoline synthesis. 

The Meth-Cohn quinoline synthesis provides a versatile and reliable entry in to 3-substituted 2-chloroquinolines. In several cases, the Meth-Cohn reaction plays a pivotal role for the preparation of biological important compounds as in the synthesis of E-ring modified derivatives of camptothecin or for the syntheses of selected NMDA antagonists with analgesic activity. ... 

The classical Vilsmeier-Haack reaction is one of the most useful general synthetic methods employed for the formylation of various electron rich aromatic, aliphatic and heteroaromatic substrates. However, the scope of the reaction is not restricted to aromatic formylation and the use of the Vilsmeier-Haack reagent provides a facile entry into a large number of heterocyclic systems. In 1978, the group of Meth-Cohn demonstrated a practically simple procedure in which acetanilide 3 (R = H) was efficiently converted into 2-chloro-3-quinolinecarboxaldehyde 4 (R = H) in 68% yield. This type of quinoline synthesis was termed the Vilsmeier Approach by Meth-Cohn. ... 

Ferrous sulfatdhoric acid Skraup-Cohn quinoline ring synthesis... 

Madelung synthesis (indole) 137 Marckwald cleavage, of furans 79 Marckwald synthesis (imidazole) 224 Meth-Cohn synthesis (quinoline) 402 Meyer s oxazoline method 183 Morin reaction 456 Mukaiyama reaction 380 Mukaiyama reagents 53, 380... 

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