Ing-Manske procedure

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... 

The total synthesis of the insect feeding deterrent peramine was accomplished by D.J. Dumas at du Pont laboratories. The Gabriel synthesis was successfully employed in the last steps of the synthesis. The primary alkyl chloride was treated with potassium phthalimide in DMF at 77-82 °C for 1.5h. The resulting A/-alkylphthalimide was cleaved in high yield using the Ing-Manske procedure. 

Khan, M. N. Suggested Improvement in the Ing-Manske Procedure and Gabriel Synthesis of Primary Amines Kinetic Study on Alkaline Hydrolysis of N-Phthaloylglycine and Acid Hydrolysis of N-(o-Carboxybenzoyl)glycine in Aqueous Organic Solvents. J. Org. Chem. 1996,... 

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. 

A commonly used modification of the Gabriel synthesis is the Ing-Manske procedure.10 Instead of removal of the phthaloyl group with aqueous base or acid, the Ing-Manske modification utilizes hydrazinolysis. It has been used in the synthesis of optically active a-amino acids 17, as illustrated by Guifa and Lingchong.11... 

Cleavage of phthaloyl protective group. The phthaloyl group is not useful for protection of the amino group of penicillins and cephalosporins because hydrazinolysis (Ing-Manske procedure, 1, 442) disrupts the azetidinone ring. Eli Lilly chemists have reported a new method of dephthaloylation that overcomes this difficulty. The phthalimido compound (1) is hydrolyzed by aqueous sodium sulfide to the corresponding phthalamic acid (2), which on dehydration... 

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