Reissert reaction

The Reissert reaction is a reaction names of organic chemistry, the functionalization of six membered Stickstoffaromaten, generally pyridine or benz -fused heterocycles such as quinoline and isoquinoline possible.

Overview reaction

Here, the overall activation and functionalization of the Reissert reaction is seen.

In this reaction, quinoline with a carboxylic acid chloride, here colored in blue and a cyanide nucleophile reacted in green, the Reissert resolved part.

Reaction mechanism

The initial activation of the aromatic compound is usually prepared by reacting the base with an aromatic acid chloride obtained ( both carboxylic acid chlorides and sulphonyl chlorides ). Acylation of the aromatic nitrogen atom is the effect of increasing the electrophilicity of the system, so that the ammonium ion is formed (specifically, pyridinium, quinolinium or isoquinolinium ) can be attacked by the cyanide nucleophile.

This nucleophilic attack leads to dearomatisation of the system to form a diene structure. If a sulfonyl chloride used as activator, the aromatic character of the system under the action of a non-nucleophilic base may be (eg, DBU ) can be restored by intramolecular redox processes. Here, the sulfonyl group ( in the illustrated example, Ts) to the corresponding sulfinic acid reduced (TSH corresponds TolSO2H, para- toluenesulfinic acid ), and obtained as a product of a functionalized derivative with a cyano group. With the use of carboxylic acid chlorides, the cyanated N-acyl- derivative may be deprotonated with a strong base (eg NaH) and be converted by alkylation and trailing alkaline hydrolysis in many other derivatives. It makes use of the acidification of Methinfunktion by the nitrile advantage.

Application

The Reissert reaction is an example for the synthesis of isoquinoline derivatives such as praziquantel.

Reissert -Henze reaction

Like the Reissert reaction itself, the Reissert -Henze reaction allows ( as Reissert Kaufmann reaction known) the synthesis of heterocyclic Cyanoaromaten. In contrast to Reissert reaction but N- oxides are used as starting material. Of pyridine -N- oxides, the reaction is self Reissert mostly unsuccessful, however, exceptions exist ( for example, 4- chloropyridine -N- oxide). The rearomatization, as in the Boekelheide rearrangement achieved similarly by the rupture of the NO bond. To this end, the N- oxide function must first be activated. In the classical protocol serves the alkylation with dialkyl sulfates (See dimethyl sulfate ), but there are also modifications that activation by silylation (See trimethylsilyl ) or phosphorylation enable (See diethylphosphorocyanidate ).