Cyanation, anodic

Zinc octaethylporphin (XXI) may be cyanated anodically at the meso positions via the cation radical by variation of the oxidation potential and the extent of electrolysis, it is possible to obtain optimum yields of mono-, di-, tri-, and tetracyanooctaethylporphyrins [132a],... 

For this class of reactions, only a few examples which proceed with reasonable diastereoselectivity are known. Allylation of a-methoxycarbamate 1, easily obtained as a 1 1 mixture of isomers by anodic oxidation of protected threonine, produces an 83 17 mixture of enantiomers on treatment with trimethyl(2-propcnyl)silanel03. Cyanation with trimcthylsilyl cyanide proceeds less stereoselectively (67 33 93 % yield). 

Scheme 9 Regioselective anodic cyanation of amine (25) by way of an electroauxiliary.

In the same way, a benzodiazepine ring can be obtained after cathodic reduction of an anodically cyanated 2-nitrobenzyl tetrahydroquinoKne (Scheme 79) [115]. 

The anodic cyanation of A-alkyl tertiary cyclic amines can give a mixture of regioisomers as observed in Scheme 109. 

Anodic cyanations of N-substituted pyrrole or 2-methylpyrrole derivatives take place in the a-position to the nitrogen atom (Scheme 111) [209] and at the side chain with 2,5-dimethyl or 2,3,4,5-tetramethylpyrrole derivatives (Scheme 112). 

A silyl group a to the nitrogen atom in tetrahydroisoquinolines and piperidines governs the regiochemistry, leads to an exclusive cyanation at this position, and additionally lowers the oxidation potential compared to the nonsilylated analogs [47]. Anodic cyanation of A-2,2,2-trifluoroethyl... 

In methanolic cyanide, N-substituted pyrroles193 are substituted in the 2-position by a cyano group on anodic oxidation. Methoxylation, which is often observed as a side reaction in the anodic oxidation in methanolic cyanide, was suppressed completely. When N-substituted pyrroles carry a methyl group in the 2- and 5-positions, a side-chain cyanation occurs.193,194... 

The evidence for transient radical-cations from N-substituted indoles has been furnished by the observation of regiocontrolled anodic cyanation of the indole ring.193,194 Substitution in the 2-position dominates, although some 3-substitution takes place. When the 1,2,3-positions of indole were blocked, no cyanation occurred, but the products of anodic oxidation have not been isolated.194... 

The electrochemical oxidation of 2,5-dimethylthiophene in various electrolytes has been investigated (71JOC3673). In non-halide electrolytes such as ammonium nitrate or sodium acetate, the primary anodic process is the oxidation of the thiophene to the cation-radical (159). Loss of a proton, followed by another oxidation and reaction with solvent methanol, leads to the product (160) (Scheme 31). When the electrolyte is methanolic NaCN, however, nuclear cyanation is observed in addition to side-chain methoxylation. Attack by cyanide ion on the cation-radical (159) can take place at either the 2- or the 3-position, leading to the products (161)-(163) (Scheme 32). 

The solubility of the components in the solvent must be sufficient. To improve the solubility, cosolvents can be used. Another possibility is the application of a two-phase system or an emulsion in the presence of phase-transfer catalysts. A two-phase system also has advantages in product isolation and continuous electrolysis procedures. A typical example is the synthesis of p-methoxy benzonitrile by anodic substitution of one methoxy group in 1,4-dimethoxybenzene by the cyanide ion (Eq. 22.21). The homogeneous cyanation system (acetonitrile, tetraethylammonium cyanide) [24] can be efficiently replaced by a phase-transfer system (dichloro-methane, water, sodium cyanide, tetrabutylammonium hydrogen sulfate) [71]. 

In this equation, E normally corresponds to hydrogen but can also be another group, e.g. -OCH3. The denotation E is used to show the interplay between nucleophiles and electrophiles in electroorganic reactions. Thus, due to the oxidative nature of the process, a nucleophile can be used as a reagent in an otherwise impossible substitution reaction. As an example of an anodic substitution process, electrochemical cyanation of an aromatic hydrocarbon can be mentioned ... 

However, this is not always the case. As an example, electrochemical cyanation 5 5-6 of an aromatic compound can be carried out by anodic oxidation in methanol-sodium cyanide (Eq. (16) ). The current yield (the yield of cyanation product based on the amount of... 

Nuclear and side chain substitution in aromatics or substitution of a -hydrogen in alkylamines is — in most cases — best rationalized by postulating radical cations as intermediates. For anodic nuclear substitution of aromatics, especially for acyloxylation, cyanation or bromination a ECnECb3 -mechanism is assumed 37,4 9,50,226,227). jc-oxidation of the aromatic to the radical cation 28, which reacts with a nucleophile Nu, e.g., acetate, cyanide, alkoxide, followed by a second electron transfer and deprotonation (Eq. (98) ) ... 

The anodic cyanation reaction allows the direct installation of cyanide without leaving groups. The cyanide acts in the electrochemical conversion similar to fluoride. After oxidation of the organic substrate the nucleophilic cyanide enters the reaction scene forming a less electron rich product which is deactivated for further anodic conversions. Therefore, the electrochemical cyanation reaction has some significance for aromatic substrates [67] (Scheme 12). 

Scheme 12 Anodic cyanation reaction 4.3.1 Cyanation of Tertiary Amines...

Yoshida K (1979) Regiocontrolled anodic cyanation of nitrogen heterocycles. Pyrroles and indoles. J Am Chem Soc 101 2116-2121... 

SSE with a high enough anodic limit (Table 4). In this way, the direct mechanisms of anodic methoxylation (nos. 3, 11, 19 and 35), and cyanation (nos. 11 and 34) have been established. For chlorination (no. 14) and bromination (no. 15) it remains to be seen whether the cases of the direct mechanism found hitherto can be generalized. 

Compound Anodic cyanation in CH3OH/NaCN at Pt Photolysis of CN /MeOHc Photolysis I—CNd of Diazotization of CN—NH2e ... 

Anodic cyanation has been shown to be a direct process by electrochemical methods in conjunction with the analysis of products from cpe experiments (nos. 11 and 34, Table 8). In addition, cyano radicals can be generated in homogeneous solution, and a comparison of processes initiated by radical cation and cyano radical initiated processes reveals the indiscriminate nature of the latter towards aromatic substrates (cf. also Williams, 1960). This is in contrast to the electrophilic nature of the radical cation process. 

Recently, evidence for the transient ex istence of cation-radicals from simple pyrroles and indoles has been furnished by the observation of anodic regiospecific cyanation of these heterocycles.455 Both heterocycles are preferentially cyanated at the 2-position. Methyl side chains at these positions are also activated to cyanation and deuteration. Indole cation-radicals have been generated by photoionization in an aqueous medium.456 Unsubstituted at N, their lifetime in neutral solution is 10-6sec before they lose the N-proton however, it is longer in more acidic conditions.456 The photophysical properties of indole, its cation-radical, and neutral radical have been the subject of a recent theoretical analysis.457 On anodic oxidation of 2,3-diphenyl indole in acetonitrile, the initially formed cation-radicals dimerize to a product identified, primarily on the basis of 13C NMR, as 3-(5-indolyl)-indolenine (141).458... 

CO2 and N2. Excess chlorine gas (i.e., chlorine which did not form hypochlorite) converted the cyanide to cyanate, which was subsequently oxidized by hypochlorite. Cadmium was precipitated from the water due to an increase in the solution pH. A platinum-plated niobium screen was the anode and a stainless steel screen was used as the cathode. At an applied potential of 6.0 V, resulting in a current of 6.0 A, the cadmium concentration decreased from 17.4mg/dm to 0.01 mg/dm, while the cyanide concentration declined from 54 mg/dm to zero in 80 min of cell operation. 

The only other alkyne the anodic oxidation of which has been studied in detail is diphenylacetylene. Again it is difficult to be certain about the mechanism involved the phenyl group and the triple bond may be electroactive but, because of the conjugation between them, it is probably more rigorous to consider electron transfer from the molecule as a whole. The relevant oxidation potential is apparently 2 V (vs. S.C.E.), the potential employed for anodic cyanation. ... 

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