2- Methylmaleic anhydride

Citraconic anhydride (or 2-methylmaleic anhydride) is a derivative of maleic anhydride that is even more reversible after acylation than maleylated compounds. At alkaline pH values (pH 7-8) the reagent effectively reacts with amine groups to form amide linkages and a terminal carboxylate. However, at acid pH (3-4), these bonds rapidly hydrolyze to release citraconic acid and free the amine (Figure 1.86) (Dixon and Perham, 1968 Habeeb and Atassi, 1970 Klapper and Klotz, 1972 Shetty and Kinsella, 1980). Thus, citraconic anhydride has been used to temporarily block amine groups while other parts of a molecule are undergoing derivatization. Once the modification is complete, the amines then can be unblocked to create the original structure. 

Itaconic anhydride (2-propen-l,2-dicarboxylic anhydride) [2170-03-8] M 112.1, m 66-68°, 67-68°, 68°, b 139-140°/30mm. Crystd from CHCl3/pet ether. Can be distd under reduced press. Distn at atm press, or prolonged distn causes rearrangement to citraconic anhydride (2-methylmaleic anhydride). If the material (as seen in the IR spectrum) contains much free acid then heat with acetyl chloride or SOCI2, evaporate... 

Methylmaleic anhydride (2.52g, 22.5mmol) was added to l.OM 3-cyclopropylideneprop-l-enyl ethyl ether in DME (25 mL). The flask was flushed with argon and closed. After 24 h at 50°C the solvent was removed completely and the residue purified by chromatography (silica gel). The product was recrystallized from hexane to give 3.24 g (61%) of colorless crystals mp 91 °C. 

Maleic anhydride, 2-methylmaleic anhydride (citraconic anhydride), and 2,3-dimethyImaleic anhydride react with proteins in a manner similar to succinic anhydride, but the products are much more labile to hydrolysis [5,6]. The reaction products of maleic anhydride and amino groups are stable at neutral pH but rapidly hydrolyze when acidified to pH 3.5. This lability increases in the order maleyl < citraconyl < dimethylmaleyl derivatives. Citraconylamides are stable enough to withstand many hours at neutral or alkaline pH s but... 

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