Phthalimide

Preparation

Phthalimide can be prepared by heating phthalic anhydride with aqueous ammonia giving 95-97% yield. Alternatively, it may be prepared by treating the anhydride with ammonium carbonate or urea. It can also be produced by ammoxidation of ortho-xylene.

Uses

Phthalimide is used as a precursor to anthranilic acid, a precursor to azo dyes and saccharin.

Alkyl phthalimides are useful precursors to amines in chemical synthesis, especially in peptide synthesis where they are used "to block both hydrogens and avoid racemization of the substrates". Alkyl halides can be converted to the N-alkylphthalimide:

C₆H₄(CO)₂NH + RX + NaOH → C₆H₄(CO)₂N-R + NaX + H₂O

The amine is commonly liberated using hydrazine:

C₆H₄(CO)₂NR + N₂H₄ → C₆H₄(CO)₂N₂H₂ + RNH₂

Dimethylamine can also be used.

Some examples of Phthalimide drugs include Thalidomide, Amphotalide, Taltrimide & Talmetoprim.

Reactivity

It forms salts upon treatment with bases such as sodium hydroxide. The high acidity of the imido N-H is the result of the pair of flanking electrophilic carbonyl groups. Potassium phthalimide, made by reacting phthalimide with potassium carbonate in water at 100 °C or with potassium hydroxide in absolute ethanol, is used in the Gabriel synthesis of primary amines, such as glycine.

Natural occurrence

Kladnoite is a natural mineral analog of phthalimide. It is very rarely found among a few burning coal fire sites.

Safety

Phthalimide has low acute toxicity with LD50 (rat, oral) of greater than 5000 mg/kg.

General reading (textbooks)

Vollhardt, K. Peter C.; Schore, Neil Eric (2002). Organic Chemistry: Structure and Function (4th ed.). New York: W.H. Freeman. ISBN 978-0-7167-4374-3. 

Finar, Ivor Lionel (1973). Organic Chemistry. 1 (6th ed.). London: Longman. ISBN 0-582-44221-4.