Phthalimide hydrazide

Is the second step of the overall reaction for R=Me (N-methylphthalimide + hydrazine —> phthalimide hydrazide + methylamine) exothermic or endothermic Will higher temperatures accelerate or inhibit the reaction Is the structure drawn above for phthalimide hydrazide its lowest-energy form or are either the imine or diimine tautomers preferred Compare energies for the hydrazide and imine and diimine tautomers. Examine the geometry of phthalimide hydrazide and any low energy tautomer, and draw the Lewis structure(s) that best describes it. Can your Lewis structures account for the energy differences Examine electrostatic potential maps for all three molecules. Which molecule(s) are stablized by favorable electrostatic interactions Which are destabilized Can this help explain the energy differences Elaborate. 

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) ... 

Benzylatnine. Warm an alcoholic suspension of 118-5 g. of finely-powdered benzyl phthalimide with 25 g. of 100 per cent, hydrazine hydrate (CAUTION corrosive liquid) a white, gelatinous precipitate is produced rapidly. Decompose the latter (when its formation appears complete) by heating with excess of hydrochloric acid on a steam bath. Collect the phthalyl hydrazide which separates by suction filtration, and wash it with a little water. Concentrate the filtrate by distillation to remove alcohol, cool, filter from the small amount of precipitated phthalyl hydrazide, render alkaline with excess of sodium hydroxide solution, and extract the liberated benzylamine with ether. Dry the ethereal solution with potassium hydroxide pellets, remove the solvent (compare Fig. //, 13, 4) on a water bath and finally distil the residue. Collect the benzylamine at 185-187° the 3ueld is 50 g. 

The phthalimide anion is a strong nucleophile, displacing a halide or tosylate ion from a good Sn2 substrate. Heating the /V-alkyl phthalimide with hydrazine displaces the primary amine, giving the very stable hydrazide of phthalimide. 

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. 

The modified procedure involves refluxing the N-substituted phthalimide in alcohol with an equivalent quantity of hydrazine hydrate, followed by removal of the alcohol and heating the residue with hydrochloric acid on a steam bath the phthalyl hydrazide produced is filtered off, leaving the amine hydrochloride in solution. The Gabriel synthesis has been employed in the preparation of a wide variety of amino compounds, including aliphatic amines and amino acids it provides an unequivocal synthesis of a pure primary amine. 

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). 

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. 

The cleavage of an Af-alkyl-l,2-benzenedicarboximide (Al-aUcyl phthalimide) is frequently carried out with base or with hydrazine, H2NNH2. The respective products of these two treatments are the 1,2-benzenedicarboxylate A or the hydrazide B. Write mechanisms for these two transformations. (Hint Review Section 20-6.)... 

The N-alkyl phthalimide product can be hydrolyzed with either aqueous acid or base to form phthalic acid and liberate the amine. However, it is difficult to hydrolyze amides (Section 21.5). A more effective method uses hydrazine to form a phthalyl hydrazide by acyl transfer. 

The exclusive product of cyclization of a 1,2-disubstituted acyl hydrazide (101) is the N-substituted phthalimide (102), the structure of which was assigned unambiguously with the aid of n.m.r/ ... 

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