Hydrazides reaction with phthalimides

The independent preparation of potassium phthabmide (from a solution of phthalimide in absolute ethanol and potassium hydroxide in 75 per cent, ethanol) may be avoided in many cases by boiling phthalimide with the halide in the presence of anhydrous potassium carbonate. The N-substituted phthalimide (I) is frequently cleav with difficulty this is often facilitated by reaction with hydrazine hydrate to give an intermediate product, which is easily decomposed by hydrochloric acid to 3deld the insoluble hydrazide of phthaUc acid (II) and the primary amine (III) ... 

Protection of amino groups from nitrous acid by acylation is not always successful, for deacylation may occur during treatment of the esters with hydrazine. Ethyl 2,6-dibenzamidoisonicotinate when treated with hydrazine gives 2,6-diMmnoisonicotinyl hydrazide the ethyl ester of phthalylglycine is similarly cleaved to gly(yl hydrazide and phthalhydrazide, a gener reaction for phthalimides (see p. 381). 

The first step of the Gabriel synthesis, the alkylation of potassium phthalimide with alkyl halides, proceeds via an Sn2 reaction. The second step, the hydrazinolysis of the A/-alkylphthalimide, proceeds by a nucleophilic addition of hydrazine across one of the carbonyl groups of the phthalimide. Subsequently, the following steps occur ringopening then proton-transfer followed by an intramolecular SnAc reaction, another proton-transfer and finally, the breakdown of the tetrahedral intermediate to give the desired primary amine and the side product phthalyl hydrazide. 

Alternatively, the required anhydrous salts may be obtained by reacting a phthalimide with about 2.5 molecular proportions of hydrazine hydrate in boiling ethyl alcohol until all the ammonia formed has been eliminated. From the reaction mixture a precipitate, consisting of the required phthalyl hydrazide salt of hydrazine, separates. Dissociation of the dried salt in the manner hereinbefore described yields the anhydrous hydrazine. 

Two substituted imides, viz. iV-triethylplumbylphthalimide and -tetra-chlorophthalimide, and one substituted hydrazide, viz. iV-triethylplumbyl-phthalohydrazide, have been described in the patent literature as fungicides 114, 115). The imides were prepared from triethyllead hydroxide and phthalimide, or tetrachlorophthalimide in ethanol. iV-triethylplumbyl-phthalohydrazide (or iV-triethyllead-2,3-dihydro-l,4-phthalazinedione as it is called in the patent) was obtained from the reaction between sodium hydroxide, phthalohydrazide, and triethyllead chloride in water. The crude hydrazide is purified by precipitating it in ethanolic solution with water. 

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