Quinoline Reissert-Henze reaction

The Reissert-Henze reaction offers a method to prepare cyanopyridines and extends the Reissert and Kaufmann reactions in the quinoline and isoquinoline series. 

Heterocyclic N-oxides such as pyridine, quinoline, or isoquinoline N-oxides can be converted into a mixture of 2- and some 4-cyanopyridines, 2- or 4-cyanoquino-lines, or 1-cyanoisoquinolines, in 40-70% yield, in a Reissert-Henze reaction, by activation of the N-oxide function by O-acylation [1] or O-alkylation [2, 3] followed by treatment with aqueous alkali metal cyanide in H2O or dioxane. 

Benzoylation constitutes the first step of the Reissert and Reissert-Henze reactions of quinoline and quinoline 1-oxides respectively, but as the benzoyl intermediates are rarely isolated this topic will be dealt with in Section 2.05.4.7. Pyridine and quinoline N-oxides react easily with p-toluenesulfonyl chloride in pyridine solution to give a variety of products which closely resemble those from the last two reactions discussed (equations 22 and 23). These belong to a family of reactions that have considerable synthetic potential and much mechanistic interest (B-67MI20501) which will be discussed collectively in Section 2.05.4.5. 

The Reissert-Henze and the Feely-Beavers-Tani reactions are considered together in this section because of their similarity. The former involves cyanation of acyloxy (formed in situ) (Scheme 113), and the latter alkoxy (Scheme 114), quaternary salts. The Reissert-Henze reaction is a facile, fairly general reaction for quinoline and isoquinoline AT-oxides (Table 19) with cyanation occurring a to the ring nitrogen. Certain substituents inhibit reaction, for example a 1-methyl group (equation 125), and others undergo replacement (Scheme 130) (81H(15)98l). Reaction of 1-methylisoquinoline 2-oxide with benzoyl chloride... 

In the Reissert-Henze reaction, quinoline 1-oxide reacts with benzoyl chloride and potassium cyanide to give 2-cyanoquinoline in good yield (Scheme 30). Pyridine 1-oxides undergo the Reissert-Henze reaction readily when the reaction is carried out in non-aqueous medium using PhCOCl-Me3SiCN (Scheme 31). Pyrimidine /V-oxides and pyrazine /V-oxides also undergo Reissert-Henze reactions. 

A -Activation in quinolines (through acylation) and pyridines (through etherification of the respective A-oxides) allows the nucleophilic addition of [ CJcyanide to the position alpha to nitrogen, resulting in the formation of 2-[ C]cyanoquinolines and [2- C]-cyanopyridines (Reissert-Henze reaction). This has been exploited for the preparation of the 2-[ C]cyano derivative 21 in good yield ". ... 

---