Imide

Physical properties

Being highly polar, imides exhibit good solubility in polar organic solvents. Unlike the structurally related acid anhydrides, they resist hydrolysis and some can even be recrystallized from boiling water.

The N–H center for imides derived from ammonia is acidic and can participate in hydrogen bonding. The N-H group is weakly acidic as indicated in the case of maleimide, with a pKa estimated at 10.

Occurrence and applications

Many high strength or electrically conductive polymers contain imide subunits, i.e., the polyimides. One example is Kapton where the repeat unit consists of two imide groups derived from aromatic tetracarboxylic acids. Another example of polyimides is the polyglutarimide typically made from polymethylmethacrylate (PMMA) and ammonia or a primary amine by aminolysis and cyclization of the PMMA at high temperature and pressure, typically in an extruder. This technique is called reactive extrusion. A commercial polyglutarimide product based on the methylamine derivative of PMMA, called Kamax, was produced by the Rohm and Haas company. The toughness of these materials reflects the rigidity of the imide functional group.

Interest in the bioactivity of imide-containing compounds was sparked by the early discovery of the high bioactivity of the Cycloheximide as an inhibitor of protein biosynthesis in certain organisms. Thalidomide, famous for its adverse effects, is one result of this research. A number of fungicides and herbicides contain the imide functionality. Examples include Captan, which is considered carcinogenic under some conditions, and Procymidone.

In the 21st century new interest arose in thalidomide's immunomodulatory effects, leading to the class of immunomodulators known as immunomodulatory imide drugs (IMiDs).

Preparation

Most common imides are prepared by heating dicarboxylic acids or their anhydrides and ammonia or primary amines. The result is a condensation reaction:

(RCO)₂O + R′NH₂ → (RCO)₂NR′ + H₂O

These reactions proceed via the intermediacy of amides. The intramolecular reaction of a carboxylic acid with an amide is far faster than the intermolecular reaction, which is rarely observed.

They may also be produced via the oxidation of amides, particularly when starting from lactams.

R(CO)NHCH₂R' + 2 [O] → R(CO)N(CO)R' + H₂O

Certain imides can also be prepared in the isoimide-to-imide Mumm rearrangement.

Reactions

For imides derived from ammonia, the N–H center is weakly acidic. Thus, alkali metal salts of imides can be prepared by conventional bases such as potassium hydroxide. The conjugate base of phthalimide is potassium phthalimide. These anion can be alkylated to give N-alkylimides, which in turn can be degraded to release the primary amine. Strong nucleophiles, such as potassium hydroxide or hydrazine are used in the release step.

Treatment of imides with halogens and base gives the N-halo derivatives. Examples that are useful in organic synthesis are N-chlorosuccinimide and N-bromosuccinimide, which respectively serve as sources of "Cl⁺" and "Br⁺" in organic synthesis.

With base followed by acid, cyclic imides open to give amido-acids. Thus, maleamic acid (HO₂CCH=CHC(O)NH₂) is derived from maleimide, succinamic acid (HO₂CCH₂CH₂C(O)NH₂) from succinimide, phthalimidic acid HO₂CC₆H₄C(O)NH₂ from phthalimide.

Related compounds

Organic compounds called carbodiimides have the formula RN=C=NR. They are unrelated to imides.

Acylureas are imides, but where one acyl group is in fact a carbamoyl: R-C(=O)-NH-C(=O)NH₂.

Isoimides

Isoimides are isomeric with imides and have the formula RC(O)OC(NR′)R″. They are often intermediates that convert to the more symmetrical imides. Isoimides upon heating rearrange to imides:

RC(O)OC(NR′)R → [RC(O)]₂NR′