Niementowski reaction

The Niementowski reaction is a name reaction from organic chemistry. It was first documented in 1895 by the Polish chemist Stefan Niementowski (1876–1925).

Overview reaction

A quinazoline is formed from anthranilic acid and an amide under the action of heat :

General

The Niementowski reaction or Niementowski synthesis is generally understood to mean the formation of quinazoline from anthralic acid and amides. However, the names Niementowski condensation and Niementowski-4-oxochinazoline synthesis are also in use. The reaction not only requires a high temperature in the range of 155–160 ° C, but also a long reaction time of around 4 hours. A higher yield can also be observed with shorter-chain amides such as formamide and acetamide , with longer-chain amides reducing the yield. This ring closure reaction could also be carried out successfully with some anthralic acid derivatives. Similar reactions or ring formations can be found in the Friedländer quinoline synthesisand the Pfitzinger reaction .

Proposed reaction mechanism

In the first step, a nucleophilic addition of the nitrogen of the anthranilic acid to the carbonyl group of the amide takes place. As a result, the nitrogen in 2 becomes positive and the electrons are accordingly flipped over, so that a primary amine is split off in the reaction from 3 to 4 . In the next step, this immediately attacks the carbonyl group of the anthralic acid nucleophilically. under the action of heat, water is split off and the amide 6 is formed. 6 can cyclize by renewed nucleophilic attack on the opposite carbonyl group. The end product 9 is obtained by renewed condensation :

Niementowski quinoline synthesis

A variation of the Niementowski reaction is the Niementowski quinoline synthesis. The anthranilic acid reacts with ketones or aldehydes to form quinoline , even at high temperatures and long reaction times . This reaction was discovered even before the Niementowski-quinazoline reaction. It is very similar to the Friedländer quinoline synthesis, but here the addition of a base as a catalyst is not necessary and there are small differences in a few intermediate steps.

The first two steps are the same as in the Niemtwoski quinoline synthesis. In the third step, however, water is split off instead of a primary amine. An electron shift takes place through an imine-enamine tautomerism , which leads to the reactive intermediate 5 . An electrophilic ring closure now takes place. Via a proton shift, the geminal diol 7 is formed via the intermediate stage 6 , which is only reasonably stable in an aqueous medium. With elimination of water, the quinoline 9 is now formed from 7 via 8 :

literature

• Zerong Wang: Comprehensic Organic Name Reactions and Reagents, Volume 2, Wiley, 2009, pp. 2054-2057, ISBN 978-0-471-70450-8 .
• Bradford P. Mundy, Michael G Ellerd, Frank G. Favaloro Jr.: Name Reactions and reagents in Organic Syntheses, second Edition, Wiley-Interscience, 2005, pp. 259,314 and 462, ISBN 0-471-22854-0 .
• The Merck Index, 9th Edition, Merck & Co., Inc., USS, 1976, ONR-63, ISBN 0911910-26-3 .

Individual evidence

1. ^ Marston Taylor Bogert, August Henry Gotthelf: Journal of the American Chemical Society . tape 22 , 1900, pp. 129–132 , doi : 10.1021 / ja02041a003 .
2. ^ Marston Taylor Bogert, William Flowers Hand: Journal of the American Chemical Society . tape 28 , 1906, pp. 94-104 , doi : 10.1021 / ja01967a012 .
3. ^ Robert C. Elderfield, Thurmond A. Williamson, Walter J. Gensler, Chester B. Kremer: Journal of Organical Chemistry . tape 12 , 1947, pp. 405-421 , doi : 10.1021 / jo01167a007 .
4. ^ Zerong Wang: Comprehensic Organic Name Reactions and Reagents, Volume 2, Wiley, 2009, p. 2055, ISBN 978-0-471-70450-8 .
5. ↑ Bradford P. Mundy, Michael G. Ellerd, Frank G. Favaloro Jr.: Name Reactions and reagents in Organic Syntheses, second Edition, Wiley-Interscience, 2005, p. 314, ISBN 0-471-22854-0 .
6. ↑ S. Niemtowski: European Journal of Inorganic Chemistry . tape 27 , 1894, pp. 1394-1403 , doi : 10.1002 / cber.18940270242 .