Phthalimide is the organic compound with the formula C6H4(CO)2NH. It is the imide derivative of phthalic anhydride. It is a sublimable white solid that is slightly soluble in water but more so upon addition of base. It is used as a precursor to other organic compounds as a masked source of ammonia.

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:

1. C6H4(CO)2NH + RX + NaOH → C6H4(CO)2NR + NaX + H2O

The amine is commonly liberated using hydrazine:

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

Alkyl amines can also be used.

Some examples of phthalimide-containing drugs include thalidomide, amphotalide, taltrimide, talmetoprim, and apremilast. With a trichloromethylthio substituent, a phthalimide-derived fungicide is Folpet.

Reactivity

The high acidity of the imido N-H is the result of the pair of flanking electron-withdrawing carbonyl groups. Both sodium phthalimide and potassium phthalimide are well known. The latter can be made by reaction of phthalimide with potassium carbonate or potassium hydroxide.. The potassium salt is used in the Gabriel synthesis of primary amines.

Preparation

Phthalimide can be prepared by heating phthalic anhydride with alcoholic 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 o-xylene.

Phthalimide can also be prepared from phthalic acid by the following process:

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 (rat, oral) of greater than 5,000mg/kg.

References

General reading