Maleic acid monoamide

Z-Maleamic acid (cis-maleic acid monoamide) [557-24-4] M 115.1, m 158-161 , 172-173 (dec), pKes, -2.65. Crystd from EtOH. IRRITANT. 

For the synthesis of sulfosuccinamates, maleic anhydride is reacted with the particular amine needed to give the required maleic acid monoamide, which can then be transformed to the sulfosuccinamate by sulfonation with sodium bisulfate in aqueous solution. The preparation of diamides is similar to that used for preparing diesters. 

The reaction partner of maleic acid anhydride can be changed. Instead of a hydroxyl group a primary or secondary amine can be used. Either monoamides or diamides can be obtained. Simple sulfation as mentioned above closes the reaction series. The variety of sulfosuccinamates (monoamides) and sulfosuccinamides (diamides) is smaller than that of sulfosuccinates. An important use lies in the field of technical applications (Fig. 2). 

The first example of a tandem Ugi-4CR/intramolecular Diels-Alder reaction was reported by Paulvannan at Affimax [95], who obtained precursors for intramolecular Diels-Alder cycloadditions by an Ugi-4CR between furan-2-carboxaldehydes, monoamides or monoesters of fumaric or maleic acids, benzylamine, and benzyl isocyanide. The Ugi-4CR adducts 172 were never isolated since they underwent... 

The BMIs are prepared according to a two-step process based on the reaction of a diamine with maleic anhydride. The first reaction is usually performed at room temperature in an aromatic, or chlorinated, or aprotic solvent. This fast and exothermic reaction leads to the monoamide (so called maleamic acid) of maleic acid. However formation of the monoamide of fumaric acid (trans-isomer) was observed [6] and the formation of the trans-isomer which does not cy-clize, has to be minimized by working at low temperature. 

It has been shown [31] that the presence of hydrophobic groups in polyampholytes can change the equilibrium between the zwitterionic and molecular forms. Alternating copolymers of vinylethyl ether and N,N-diethylaminopropyl-monoamide of maleic acid preferentially exist in the charged form (I) but the replacement of ethyl radicals by two bulky butyl radicals stabilizes the uncharged molecular form (II). 

A similar behavior is observed from competitive dissociations of protonated monoamides of maleic and fumaric acids which lead to the formation of [MH H2O] and [MH NH3] +, respectively. They are accompanied by the presence of NH, although the loss of water corresponds to the base peak from the Z stereochemistry but is of lower abundance from the E isomer. From fumarate monomethyl ester or monoamide, the major pathway for protonated molecule dissociation corresponds to the loss of XH as methanol or ammonia, respectively, which suggests that the modified carboxylic group is the preferred protonation site (Scheme 17.8). Consequently, the favorable loss of water from the Z isomers (not only for maleic acid, but also for the monoester and monoamide derivatives) indicates that the water loss rate constant, via 1,6-H" transfer, is much larger than that occurring from the E isomer which involves either 1,3-H" transfer (a symmetry forbidden process) or a multistep proton migration which is characterized by higher transition state level(s) (Scheme 17.8). 

Amidation. Reaction of maleic anhydride or its isomeric acids with ammonia [7664-41-7] (qv), primary amines (qv), and secondary amines produces mono- or diamides. The monoamide derivative from the reaction of ammonia and maleic anhydride is called maleamic acid [557-24-4] (8). Another monoamide derivative formed from the reaction of aniline [62-53-3] and maleic anhydride is maleanilic acid [555-59-9] (9). 

Monoesters of symmetric dicarboxylic acids can be prepared either by monoesterification of a diacid [1] or by monosaponification of a diester. Dicarboxylic acids which can form five- or six-membered cyclic anhydrides are readily transformed into monoesters via these intermediates, but for diacids which cannot be converted into such cyclic anhydrides monosaponification of diesters seems to be more reliable than selective monoesterification. Monoesters or monoamides of succinic, maleic, glutaric, or related diacids can be rather unstable, because of the dose proximity of a carboxyl group (see Section 3.3). 

---