Reduction of the Diazo Group

Introduction. When diazonium salts are reduced, they form aryl-hydrazines (RNHNH2), which are regarded as derivatives of hydrazine, H2N.NH2. When a diazonium salt is added to a solution of bisulfite, it forms the diazonium sulfonate, which, when heated, is reduced by the excess bisulfite to phenylhydrazine sulfonate. Addition of hydrochloric acid ves the phenylhydrazine hydrochloride, which is slightly soluble in an excess of hydrochloric acid. These reactions are represented by the following equations  

In order to reduce an orange dye which is formed when the diazonium salt is added to the bisulfite solution, a small amount of zinc and acetic acid is added. To prepare the base, the hydrochloride is treated with excess 30 per cent sodium hydroxide solution, and the oily base is extracted with ether. The ethereal extract is dried and, after removal of ether, is distilled under reduced pressure. Substituted phenylhydrazines, such as p-nitrophcnylhydrazine and p-bromophenylhydrazine, are prepared in the same manner. Arylhydrazines are strong bases forming characteristic salts, which are important reagents in the identification of aldehydes, ketones, and sugars (see preparation of phenylhydrazones and osazones). 

Place the wet crude salt in a beaker, cool by means of running water, and add (using the hood) sufficient solution of 30 per cent sodium hydroxide to decompose the salt and cause the base to rise as an oil to the top. Avoid breathing the fumes given off by phenylhydrazine, as they are very toxic. Cool, and transfer to a separatory funnel, washing the beaker with 20 ml of ether. Extract twice with 50-ml portion of ether, and dry the ethereal solution of the base with solid sodium hydroxide. Transfer the ether solution into a 250-ml Claisen flask and distill off the ether by means of a water bath. Remove the bath, and arrange for distillation under reduced 

Caution Phenylhydrazine is highly poisonous. Wash at once any liquid which has come in contact with the skin first with a 2 per cent acetic acid solution and then with soap and water. 

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Diazotisation of anthranilic acid and immediate reduction of the diazo group is a very simple route to indazolin-3-one. Hydrolysis of the amide unit of isatin, then diazotisation and reduction produces indazole-3-carboxyhc acid adding the diazonium salt solution to the reducing mixture minimizes the formation of byproduct indazolin-3-ones. ... 

Diazo Coupling Reactions. Alkylphenols undergo a coupling reaction with dia2onium salts which is the basis for the preparation of a class of uv light stabilizers for polymers. The interaction of orxv i -nitrobenzenediazonium chloride with 2,4-di-/ r2 -butylphenol results in an azo-coupled product (30). Reduction of the nitro group followed by m situ cyclization affords the benzottiazole (31) (19). 

Aryldiazonium salts, usually obtained from arylamines, undergo replacement of the diazonium group with a variety of nucleophiles to provide advantageous methods for producing aryl halides, cyanides, phenols and arenes by reductive removal of the diazo group. Coupling reaction of aryldiazonium salts with phenols or arylamines give rise to the formation of azo dyes. 

The yield depends upon the molar ratio of hypophosphorous acid to diazonium salt.81,82 If it is assumed that hypophosphorous acid undergoes oxidation to phosphorous acid, then one molecule of hypophosphorous acid mil be required for the reduction of each diazo group. 

On reduction of the nitro-group, and treating with nitrous acid, a diazo-compound is obtained, which with jS-naphthol yields a tertiary azo-compound —... 

Reduction of the carbonyl group in cyclic and acylic 2-diazo- 1,3-diketones (129, 135-137, 143, 146, and 196) with NaBH in aqueous alcoholic solution, followed by hydrolysis of the reaction mixture over wet silica gel, affords the corresponding 3-hydroxy-2-diazoketones (190-195 and 197) in 58-87% yield.85 Steric hindrance at a to the carbonyl decreases the yield of reduced products.85... 

Another side chain attachment pathway takes advantage of the fact that / -ketoesters can be coupled readily with baccatin III (302). The f3-ketoester 8.1.18 was converted to its O-benzyloxime, and then in a key step to the diazo derivative 8.1.19. Reductive hydrolysis of the diazo group gave epimers 8.1.20 and 8.1.21 in a 1 2 ratio, and the major epimer 8.1.21 was successfully converted to taxol using oxazine ring formation to invert the stereochemistry at C-2 (303). 

This correlation (Scheme 13.10) had originally been performed by Leithe,W. Chem. Ber., 1931, (54,2827 by benzoylation of the (-)-l-phenylethylamine, nitration of the aromatic ring of the resulting At-benzoyl derivative, reduction of the nitro group to the amine, diazotization of the amine and conversion of the diazo compound to the phenol. Oxidation of the phenol with chromic anhydride in acetic acid yielded the A -benzoyl derivative of (-F)-alanine—by direct comparison to that compound. 

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