Cyanide reaction with diazonium compounds

As it is well known, nucleophilic substitution of a C-X bond, one of the key synthetic reactions with aliphatic compounds is severely limited with aromatic derivatives, where it occurs thermally only with electron-withdrawing substituted compounds and/or under severe conditions. Alternatives include time honored reactions involving the phenyl radical generated by decomposition of diazonium salts after a reductive step, such as the Meerwein and the Gomberg-Bachmann reactions, as well as the (often photoinitiated) SrnI reaction, where a (usually weak, e.g. carbon-iodine) bond is cleaved after monoelectronic reduction to give an aryl radical as the active inter-mediate that adds to an enolate, cyanide or other nucleophiles (and thus again with an aryl radical as the key intermediate. Scheme S). ... 

Compared to diazonium salts, diazo compounds are generally much less reactive towards nucleophiles than towards electrophiles. As a result of this azo coupling reactions of diazo compounds are the exception rather than the rule. Electron withdrawing substituents on the diazo carbon increase the reactivity towards nucleophiles. Consequently the ability to undergo azo coupling reactions increases from diazomethane to diazocarbonyl- and 2-diazo-l, 3-dicarbonyl compounds. Among the earliest reactions known were those with cyanide and sulfite ions Tertiary phosphines, as opposed to amines, can form stable addition complexes with diazoalkanes probably due to the ability of phosphorus to stabilize the betaine with its empty d orbitals (6). 

Many aryl nitriles are obtained from diazonium salts by treatment with copper(l) cyanide. Hydroxy and amino nitriles are obtained from addition reactions to carbonyl compounds. 

Nucleophilic substitution reactions may involve several different combinations of charged and uncharged species as reactants. The equations in Scheme 4.1 illustrate the four most common charge types. The most common reactants are neutral halides or sulfonates, as illustrated in Parts A and B of the scheme. These compounds can react with either neutral or anionic nucleophiles. When the nucleophile is the solvent, as in Entries 2 and 3, the reaction is called a solvolysis. Reactions with anionic nucleophiles, as in Entries 4 to 6, are used to introduce a variety of substituents such as cyanide and azide. Entries 7 and 10 show reactions that involve sulfonium ions, in which a neutral sulfide is the leaving group. Entry 8 involves generation of the diphenylmethyl diazonium ion by protonation of diphenyldiazomethane. In this reaction, the leaving... 

Conversion of diazonium compounds to aryl chlorides, bromides, or cyanides is usually accomplished using cuprous salts, and is known as the Sandmeyer reaction. Since a CN group is easily converted to a CO2H group (eq. 10.13), this provides another route to aromatic carboxylic acids. The reaction with KI gives aryl iodides, usually not easily accessible by direct electrophilic iodination. Similarly, direct aromatic fluorination is difficult, but aromatic fluorides can be prepared from diazonium compounds and tetrafluoroboric acid, HBF4. 

Reaction of cyanide with aromatic diazonium compounds (Section 23.8E). 

Diazonium salts (157) (Equation (1)) have been reacted with 2-chloro- 1,3-dicarbonyl compounds yielding heterocycles (158) (50-75%) <82JCS(Pl)989>. In a similar reaction sequence (Scheme 3), salt (157) yielded products (160) and/or (161) with activated methylene compounds <89ZN(B)95i>. The formation of compound (160) involves elimination of a molecule XH, which is usually hydrogen cyanide. 

Diazonium ions react with all known nucleophiles. The addition of hydroxide, alkoxide, cyanide and sulfite ions does not belong to the subject of this review, but the formation of diazoamino compounds (1,3-triazenes) formed with ammonia, primary and secondary amines does. In analogy with the other reactions discussed in this paper, where carbon atoms are the site of attack by diazonium ions (C-coupling), these reactions are called N-coupling reactions. 

A -oxide which is easily reduced to codeine with sulphur dioxide [303]. The 0-methylation of certain Erythrina alkaloids has been carried out in a similar manner [304]. A -Oxidation has also been used to protect tertiary ring nitrogen atoms in heteroaromatic compounds. Protonation of the ring nitrogen atom in 4- (and 2-) aminopyridines renders their diazonium salts very susceptible to hydrolysis, thus they cannot be converted into cyanides by the Sandmeyer reaction. The corresponding TV-oxides may, however, be used in the normal way and the oxide function removed at a later stage, as in the sequence (63) (64) used by Berson and Cohen in studies on ipecac... 

Gatterman reaction ORG CH em 1. Reaction of a phenol or phenol ester, and hydrogen chloride or hydrogen cyanide, i n the presence of a metallic chloride such as aluminum chloride to form, after hydrolysis, an aldehyde. 2. Reaction of an aqueous ethanolic solution of diazonium salts with precipitated copper powder or other reducing agent to form diaryl compounds. gad-3r-man re,ak-sh3n) gaultheria oil See methyl salicylate. g6l thir-e-3, 6il)... 

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