Aromatic acids from cyanides

Aromatic Acids.—hs, the cyanides are acid nitriles yielding the acids on hydrolysis, the above reaction gives us a means of passing from primary amines through the diazo compound to the acid nitrile and finally to the corresponding aromatic acid. 

In the aromatic series the direct conversion of acid amides into acid nitriles does not take place readily but the acid itself is made from the acid amide by the reverse process as indicated above, viz., by hydration to the ammonium salt of the acid, which then yields the acid. A related method, however, is used for preparing acids from anilides of formic acid. Aniline being an ammonia compound yields acid-amidelike products with aliphatic acids, e.g. acet anilide, CH3—CO—NH— CeHs (p. 556). Such a compound can not, however, lose water in the same way as the acid amide in the above reaction for the ammonia residue in an anilide contains only one hydrogen. Nevertheless anilides lose water but in a different way. In the case of the anilide of formic acid, i.e. formanilide, H—CO—NH—CeHs, the loss of water results in a compound in which the carbon and nitrogen remain linked to the benzene ring and an iso-cyanide or iso-nitrile is formed. The isonitrile is readily converted into the nitrile and the acid may then be obtained from that. 

C7H10O3 Mr 142.15, has been found in, e.g., lovage and roast coffee. It has a bouillon-like, coffee and lovage aroma, depending on its concentration. It can be synthesized by condensation of 2-oxobutanoic acid (from acrylic aldehyde with acetic anhydride and sodium cyanide, followed by reaction with methanol/hydrochloric acid) with methanol/sodium methylate and subsequent decarbomethoxylation [200]. It is used for aromatization of food. 

The reaction is applicable to almost all aromatic diketones, but in the aliphatic series it is restricte4 to isolated cases.164 When carrying out the benzilic acid rearrangement it is necessary to ensure that the diketone is free from cyanide, because Dilthey and Scheidt165 have shown that in the presence of cyanide ions benzil is cleaved hydrolytically to benzaldehyde and benzoic acid. 

Hydrolyse the substance by heating it under reflux with concentrated alkali (alkyl cyanides) or 70 % sulphuric add (aryl cyanides) for about an hour. Liberate the organic add from the cooled hydrolysate by addition of excess of mineral acid (aliphatic acids) or by careful addition to water (aromatic acids), and identify the product. 

Aromatic nitriles (or aryl cyanides) can be obtained by methods (1) and (3). but not by method (2). In addition, aromatic nitriles can be prepared by two other methods, (a) from the corresponding diazo compound by Sandmeyer s Reaction (p. 189), (b) by fusing the corresponding sulphonic acid (or its salts)... 

The electrophile 4 adds to the aromatic ring to give a cationic intermediate 5. Loss of a proton from 5 and concomitant rearomatization completes the substitution step. Subsequent hydrolysis of the iminium species 2 yields the formylated aromatic product 3. Instead of the highly toxic hydrogen cyanide, zinc cyanide can be used. The hydrogen cyanide is then generated in situ upon reaction with the hydrogen chloride. The zinc chloride, which is thereby formed, then acts as Lewis acid catalyst. 

For the in situ preparation of the required arenediazonium salt from an aryl amine by application of the diazotization reaction, an acid HX is used, that corresponds to the halo substituent X to be introduced onto the aromatic ring. Otherwise—e.g. when using HCl/CuBr—a mixture of aryl chloride and aryl bromide will be obtained. The copper-(l) salt 2 (chloride or bromide) is usually prepared by dissolving the appropriate sodium halide in an aqueous solution of copper-(ll) sulfate and then adding sodium hydrogensulfite to reduce copper-(ll) to copper-(1). Copper-(l) cyanide CuCN can be obtained by treatment of copper-(l) chloride with sodium cyanide. 

Carbon monoxide, hydrogen cyanide, and nitriles also react with aromatic compounds in the presence of strong acids or Friedel-Crafts catalysts to introduce formyl or acyl substituents. The active electrophiles are believed to be dications resulting from diprotonation of CO, HCN, or the nitrile.64 The general outlines of the mechanisms of these reactions are given below. 

Sandmeyer s synthesis of aromatic nitriles is far more elegant than the removal of water from the ammonium salts of carboxylic acids, which latter reaction is also applicable to benzene derivatives. In particular, the former synthesis permits of the preparation of carboxylic acids via the nitriles, and so provides a complete substitute for Kolbe s synthesis (alkyl halide and potassium cyanide), which is inapplicable to aromatic compounds. The simplest example is the conversion of aniline into benzoic add. The converse transformation is Hofmann s degradation (benzamide aniline, see p. 152). 

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