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. 

One can extend the strategy employed in the Reissert-Henze reaction to nucleophiles other than cyanide. Phosphorus-based systems were employed in the... 

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. 

Reinforcing materials, 20 455t Reissert compounds, 22 185, 186, 201 Reissert-Henze reaction, 22 99 Relationships, as an aspect of the technical service function, 24 348 Relative abundance, 25 648, 649-650 Relative atomic ratios, determination of, 24 93-94... 

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 work described in the next section on the family of Reissert reactions might provide a clue to the direction of future work with these interesting phosphorus derivatives of pyridine. The reactions discussed above bear direct comparison with the Reissert-Kaufmann (Scheme 106), Feely-Beavers-Tani (equations 113 and 114) and Reissert (Schemes 107-110) reactions. An analogue of the Reissert-Henze reaction has yet to be reported. 

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... 

Table 19 Reaction of Af-Oxides with Cyanide Ions Reissert-Henze Reactions... 

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. 

Reissert compounds have been prepared from compounds (21) and (23) using either trimethylsilyl cyanide or potassium cyanide as the cyanating agents. Yields ranged from 57% to 71 % <84JHCl 119, 86JHC545). The N-oxides of some thieno[2,3-6]pyridine derivatives, as shown in Equation (8), have been used in the Reissert-Henze reaction to produce cyano-substituted products <83JHC213>. 

Even poor nucleophiles such as the amides 46 can react with azines in the presence of alkynes as activating agents [59, 60]. Various nucleophiles (including alkoxides, thiols, amines and nitrogen heterocycles) were recently employed in a related process with Ai-oxide azaindoles (Reissert-Henze reaction. Scheme 10). In the process, the oxygen is alkylated with dimethyl sulfate and, after the nucleophilic attack, methanol is released to aromatize the initial adduct [61,62]. Following similar mechanistic trends, V-heteroatom-activated azines afford the corresponding substituted adducts. Likewise, W-tosylated isoquinoline [63, 64] and W-fluoropyridinium salts [65] are also reactive substrates in Reissert-Henze type processes. 

Modified conditions have been developed for the preparation of cyanoheteroarenes from hetero-arene Woxides by the Reissert-Henze reaction, using TMSCN and DBU (Equation (9)). DBU as base is much more productive than triethylamine, which gave only 37% yield in 180 minutes compared to 76% in 40 minutes for the example shown <92H(33)2l l >. The use of tri- -butyltin cyanide with benzoyl chloride for the preparation of Reissert compounds when applied to phthalazine gave... 

TABLE 1 Reissert-Henze Reaction with Triazole 11... 

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