Phthalimides Hofmann reaction

It is prepared by the action of sodium hydroxide and sodium hypochlorite on phthalimide (Hofmann reaction). When heated with soda lime it gives aniline. 

Anthranilic acid. This substance, the ortho amino derivative of benzoic acid, may be conveniently prepared by the action of sodium hypobromite (or sodium hypochlorite) solution upon phthalimide in alkaline solution at 80°. The ring in phthalimide is opened by hydrolysis to phthalamidic acid and the latter undergoes the Hofmann reaction (compare Section 111,116) ... 

An important application of the Hofmann reaction occurs in the first technical synthesis of indigo and consists in the degradation of phthalimide to anthranilic add. See p. 372. 

For the preparation of anthranilic acid the starting material is phthalimide, the cyclic imide ring of which is opened by alkaline hydrolysis in the first step of the reaction to give the sodium salt of phthalimidic acid (the half amide of phthalic acid). The intermediate undergoes the Hofmann reaction in the manner outlined on p. 783 yielding o-aminobenzoic acid (anthranilic acid). 

The reaction is accomplished by simply heating together phthalic anhydride and ammonium carbonate. Phthalimide then hydrolyzes with potassium hydroxide yielding the potassium salt of phthalamidic acid and this acid amide compound undergoes the Hofmann reaction (pp. 148, 685) with bromine (or chlorine) and potassium hydroxide by which one of the carboxyl groups is replaced by the amino group yielding amino benzoic acid or anthranilic acid. 

Hofmann Reaction.—In the reaction with phthalic acid or anhydride and ammonia the phthalamidic acid may be isolated without going on to phthalimide. In this case the action of potassium hydroxide is simply neutralization and formation of the above salt. The Hofmann reaction with phthalamidic acid may be represented in steps as follows ... 

Since the nitro-add corresponding to the o-amido benzene add is difficult to obtain, and phthalimide is easily prepared, the Hofmann reaction in this case gives a very convenient method of preparation for the amido-add. 

Maxuicu Yieuib of Anthbanujc Acn>s Obtainable from Phthalimides bt the Hofmann Reaction with Alkaune Htpochlortte and Hypobbomite... 

Phenylethylamine has been made by a number of reactions, many of which are unsuitable for preparative purposes. Only the most important methods, from a preparative point of view, are given here. The present method is adapted from that of Adkins,1 which in turn was based upon those of Mignonac,2 von Braun and coworkers,3 and Mailhe.4 Benzyl cyanide has been converted to the amine by catalytic reduction with palladium on charcoal,5 with palladium on barium sulfate,6 and with Adams catalyst 7 by chemical reduction with sodium and alcohol,8 and with zinc dust and mineral acids.9 Hydrocinnamic acid has been converted to the azide and thence by the Curtius rearrangement to /3-phenyl-ethylamine 10 also the Hofmann degradation of hydrocinnamide has been used successfully.11 /3-Nitrostyrene,12 phenylthioaceta-mide,13 and the benzoyl derivative of mandelonitrile 14 all yield /3-phenylethylamine upon reduction. The amine has also been prepared by cleavage of N- (/3-phenylethyl) -phthalimide 15 with hydrazine by the Delepine synthesis from /3-phenylethyl iodide and hexamethylenetetramine 16 by the hydrolysis of the corre-... 

A further important product from phthalimide is anthranilic acid. Hofmann-degradation of phthalimide with sodium hypochlorite produces the sodium salt of anthranilic acid in an exothermic reaction. This salt is transformed into free anthranilic acid by the reaction with sulfuric acid. 

Phthalimides 23 are transformed into a mixture of carbamates 25a and arylamines 25b by reaction with iodobenzene in the presence of /mCPBA and TsOH H20 (Scheme 9) [9]. The suggested mechanism implies the formation of imide-A, -iodane intermediates 24 which undergo alcoholysis followed by Hofmann-type rearrangement to yield 25. 

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