Ing-Manske reaction

A strong base attacks a cyclic imide to open the imide ring system, which is a modified "Ing-Manske" reaction. Ing, H. Manske, R. J. Chem. Soc. 1926, 2348. 

The best method of preparing hydrazides is by the reaction of hydrazines with esters. Acyl halides and amides may also be reacted with hydrazines. In the case of the Ing-Manske reaction, N-substituted phythalimides are reacted with hydrazine to generate a primary amine and the cyclic phthalhydrazide. 

NOTE JV-/-Butylphthalimide can react with hydrazine hydrate and upon acidification of the reaction mixture t-butylamine is obtained in 89-94% yield [3,4] (an example of the Ing-Manske reaction). 

The reaction of potassium phthalimide 1 with an alkyl halide 2 leads to formation of a N-alkyl phthalimide 3/ which can be cleaved hydrolytically or by reaction with hydrazine (Ing-Manske variant) to yield a primary amine 5. This route owes its importance as a synthetic method to the fact that primary amines are prepared selectively, not contaminated with secondary or tertiary amines. 

The hydrolytic cleavage is usually slow, and requires drastic reaction conditions. A more elegant method is presented by the Ing-Manske procedure, where the A-alkylated imide is treated with hydrazine under milder conditions. In addition to the desired amine 5, the cyclic phthalic hydrazide 6 is then formed ... 

It is obvious that the primary amines formed in this reaction will be uncontaminated by secondary or tertiary amines (unlike 10-44). The reaction is usually rather slow but can be conveniently speeded by the use of a dipolar aprotic solvent such as DMF or with a crown ether. Hydrolysis of the phthalimide, whether acid or base catalyzed (acid catalysis is used far more frequently), is also usually very slow, and better procedures are generally used. A common one is the Ing-Manske procedure,in which the phthalimide is heated with hydrazine in an exchange... 

Phthalimides are relatively stable under both acidic and basic conditions but are easily cleaved by nucleophiles. Its cleavage is often accomplished using hydrazine according to the Ing-Manske procedure of the Gabriel reaction. 

Gabriel condensation, 124-126 Ing-Manske modification, 124-126 Gattermann condensation, 50 Goldberg reaction, 93 Grignard coupling, 14-15,17 Grignatd method, 54-56 Grignard reaction, 31,50, 59,94,176,187, 246-248... 

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