Meth-Cohn

O. Meth-Cohn, Org. Chem. Sulphur Selenium Tellurium., 4, 828 (1979). 

There are, however, some crown type compounds which contain no structural feature except the thiophene subunit, and these deserve some comment here. This is especially true since one of these compounds was prepared very early in the history of crown compounds. Ahmed and Meth-Cohn were interested in sulfur analogs of the porphyrin ring system and prepared compound 7 in 1969 by the method shown in Eq. 

The Meth-Cohn quinoline synthesis involves the conversion of acylanilides 1 into 2-chloro-3-substituted quinolines 2 by the action of Vilsmeier s reagent in warmed phosphorus oxychloride (POCI3) as solvent. ... 

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. ... 

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... 

Rajanna et al. also demonstrated dramatic rate enhancements when ultrasonically irradiated Meth-Cohn quinoline syntheses were performed again, deactivated aeetanilides 20 were found to undergo efficient cyclisation in good yield. 

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. 

The Reverse Vilsmeier Approach to the synthesis of quinolinium salts is discussed in Meth-Cohn, O. Taylor, D.L. Tetrahedron 1995, 51, 12869. 

Meth-Cohn, O Narine, B. Tamowski, B. J. Chem. Soc., Perkin Trans. 1 1981, 1520. 

R. A. Abramovitch, Clemson, South Carolina A. T. Balaban, Bucharest, Romania A. J. Boulton, Norwich, England H. Dorn, Berlin-Bohnsdorf, Germany J. Elguero, Madrid, Spain S. Gronowitz, Lund, Sweden E. Lukevics, Riga, Latvia O. Meth-Cohn, Sunderland, England V, I. Minkin, Rostov-on-Don, Russia... 

MI2 O. Meth-Cohn, in Comprehensive Organie Chemistry (D. Barton and... 

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