To fumaric acid

Reactions. Mahc acid undergoes many of the characteristic reactions of dibasic acids, monohydric alcohols, and a-hydroxycarboxyUc acids. When heated to 170—180°C, it decomposes to fumaric acid and maleic anhydride which sublimes on further heating (see Maleic anhydride, maleic acid, AND FUMARIC acid). MaUc acid forms two types of condensation products linear malomalic acids and the cycHc dilactone or maUde it does not form an anhydride. 

Maleic and fiimaric acids have physical properties that differ due to the cis and trans configurations about the double bond. Aqueous dissociation constants and solubiUties of the two acids show variations attributable to geometric isomer effects. X-ray diffraction results for maleic acid (16) reveal an intramolecular hydrogen bond that accounts for both the ease of removal of the first carboxyl proton and the smaller dissociation constant for maleic acid compared to fumaric acid. Maleic acid isomerizes to fumaric acid with a derived heat of isomerization of —22.7 kJ/mol (—5.43 kcal/mol) (10). The activation energy for the conversion of maleic to fumaric acid is 66.1 kJ/mol (15.8 kcal/mol) (24). 

Maleic acid can be thermally dehydrated to maleic anhydride (69) or dehydrated through azeotropic distillation. Solvents such as xylenes (70) or dibutyl phthalate [84-74-2] (71) are preferred but conditions must be carefully adjusted to avoid isomerization to fumaric acid. 

Isomerization. Maleic acid is isomerized to fumaric acid by thermal treatment and a variety of catalytic species. Isomerization occurs above the 130 to 140°C melting point range for maleic acid but below 230°C, at which point fumaric acid is dehydrated to maleic anhydride. Derivatives of maleic acid can also be isomerized. Kinetic data are available for both the uncatalyzed (73) and thiourea catalyzed (74) isomerizations of the cis to trans diacids. These data suggest that neither carbonium ion nor succinate intermediates are involved in the isomerization. Rather, conjugate addition imparts sufficient single bond character to afford rotation about the central C—C bond of the diacid (75). 

The presence of a hot spot is known to generate free radicals. Thus, reactions that are initiated by the presence of free radicals can be carried out with less or no catalyst, as has been discovered in the case of isomerization of maleic acid to fumaric acid with an 3 to 16 fold increase in the isomerization rates at reduced catalyst (thiourea) concentrations (Muzumdar, 1988). 

Majumdar S, Pandit AB (1998) Study of catalytic isomerisation of Maleic acid to Fumaric acid Effect of Ultrasound. Ind Chem Engr 40 187-192... 

Elving, Rosenthal, Hayes and Martin 41> studied the electrochemical reduction of bromofumaric acid(27) and bromomaleic acid(28)in aqueous solution over a wide pH range. It was claimed that reduction of 27 proceeds stereo-specifically to fumaric acid, and that reduction of 28 affords mixtures of maleic and fumaric acids. Because of the polar and hydrogen-bonding properties of the carboxyl groups in 27 and 28, the relation of these results to those of Fry and Mitnick l6) is unclear. 

S. Except for oxido-reductases, transferases, and hydrolases, most ligases (enzymes that catalyze bond formation) are entirely substrate specific. Thus, fumarate hydratase (or fumarase) reversibly and stereospecifically adds water to fumaric acid to produce (S)-( — )-malic acid only (8) (Figure 1), and another enzyme, mesaconase, adds water to mesaconic acid to form (+ )-citramalic acid (9) (Figure 2). Although no extensive studies are available, it appears that neither fumarase nor mesaconase will add water stereospecifically to any other a,(3-unsaturated acid. 

The enzyme fumarase catalyses the stereospecific iram -addition of water to fumaric acid giving (5)-malic acid, and the reverse reaction, the rrans-elimination of water from (S )-malic acid ... 

Molecular forms that arise as a result of rotation around freely rotatable bonds are known as conformers. Even small molecules can have different conformations in solution. In the two conformations of succinic acid illustrated opposite, the atoms are arranged in a similar way to fumaric acid and maleic acid. Both forms are possible, although conformation 1 is more favorable due to the greater distance between the COOH groups and therefore occurs more frequently. Biologically active mac-... 

L-aspartic acid by ammonia addition to fumaric acid by aspartase (from E. coli)... 

L-malic acid by addition of water to fumaric acid by fumarase from Brevibacterium... 

The transformation of maleic acid to fumaric acid is accelerated by the presence of colloidal sulphur.2... 

Fumaric Aero Inhibition. Another means of preventing malo-lactic fermentation is to add fumaric acid after alcoholic fermentation is complete (45, 46, 47,48). The inhibition is relative and its extent is dependent on the amount added. The susceptibility to fumaric acid is also dependent on the strain of malo-lactic bacteria tested (49). However, we know of no case where fumaric acid addition at the levels suggested by Cofran and Meyer (45) (about 0.05%) did not delay malo-lactic fermentation under normal winemaking conditions. This includes several experiments from our pilot winery (50). Nevertheless, we have not been hasty to recommend the use of fumaric acid as an inhibitor because 1) of the difficulty in solubilizing the acid in wine 2) we do not know the mechanism of action of its inhibition [Pilone (47, 48) has shown that the bacteria metabolize low levels of fumaric acid to lactic acid but, at inhibitory levels at wine pH, the acid is bactericidal] and 3) of the desirability of minimizing the use of chemical additives. 

Exercise 10-11 Show by projection formulas the stereochemical course you would expect for the acid-catalyzed addition of D20 to fumaric acid to give the deuterated... 

Exercise 10-12 The hydration of fumaric acid catalyzed by fumarase in D20 leads to malic acid with only one C-D bond, which is selectively removed when malic acid is enzymatically reconverted to fumaric acid. The configuration of deuteriomalic acid prepared in this way has been shown to correspond to the following projection formula ... 

Electrosynthesis is useful when the electrode reaction is stereo specific. For example, for a,a -dibromosuccinic acids, the threo form of both the free acid and its anions is reduced to fumaric acid. On the contrary, the erythro epimer is reduced to fumaric acid only in the undissociated form and as a dibasic anion. The univalent anion is at least partly reduced to maleic acid. Both threo and erythro epimers of dialkyl esters of dibro-mosuccinic acid are reduced, similarly to the undissociated free acids, to only the dialkyl ester of fumaric acid (134,135). 

Owing to the commercialization of Aspartame the demand for i-aspartic acid increased steeply. i-Aspartate can be produced by enantioselective addition of ammonia to fumaric acid catalyzed by aspartase (E.C. 4.3.1.1) (Figure 7.17). 

The fact that, though addition of D20 to fumaric acid is reversible, it yields only a monodeuterated malic acid and involves recovery of nndeuterated fumaric acid only, indicates that the addition and elimination steps are stereospecific and that they proceed with the same stereochemistry. The formation of the erythro isomer of... 

With the use of rice bran as a nitrogen source, we studied the effect of phosphate, magnesium, zinc, and iron on fumaric acid production. Although magnesium, zinc, and iron did not cause any effect (Mg2+ trials 1 and 4, Zn2+ trials 1 and 3, Fe2+ trials 1 and 2), phosphate was crucial to fumaric acid production (trials 12 and 16). 

When these are cooked together, maleic anhydride isomerizes to fumaric acid, and they condense to form low-molecular-weight propylene fiimarate phthalate copolyester oligomers. These are mixed with styrene monomer, reinforced by glass fibers, usually extended with low-cost fillers, and cured by peroxide to form rigid strong products which are very resistant to impact and heat (Table 15.20). 

In Escherichia colF and Salmonella typhimurium have been detected enzymes which split iV-[5 amino-l-(5-0-phospho-D-ribofuranosyl)-4-imida-zolecarbonyl]-L-aspartic acid to fumaric acid and 5-amino-4-imidazolecar-boxamide ribonucleotide. 

Since fumaric acid is biodegradable, benzene may be electrochemically degraded only partially to fumaric acid, which is then biodegraded. This process requires fewer electrons (30 vs 9) and thus represents a much lower cost, since biodegradation is normally the cheapest treatment alternative for organic wastes. 

Another instance of a reaction catalyzed by small concentrations of free radicals is the interconversion of geometrical isomers. The cis-trans isomerization of maleic to fumaric acids... 

Scheme 3 Addition of D2O to fumaric acid to form malic acid...

Malonic acid is a classical example of a true competitive inhibitor. Malonic acid inhibits succinic dehydrogenase, which catalyzes the oxidation of succinic acid to fumaric acid, as shown below. 

The enantioselective addition of water to fumaric acid gives malic acid [118]. This highly efficient biocatalytic reaction is catalyzed by a fumarase. Although substrate tolerance of this enzyme is narrow, high enantioselectivities are obtained. 

Now predict the outcome of the addition of bromine to fumaric acid, which is the trans isomer of maleic acid. 

In this case, the meso isomer is formed. For the sake of completeness, we will continue this exercise by adding an unsymmetrical molecule, AB, to fumaric acid. Suggest the stereochemistry of this product. 

L-Malic acid by water addition to fumaric acid Fumarase (Brevibacterium)... 

Chatteijee, S. Pedireddi, V. S. Rao, C. N. R., Unexpected Isomerization of Maleic Acid to Fumaric Acid on Co-crystallization with 4,4 -bipyridine Tetrahedron Lett. 1998, 39, 2843. 

Properties Colorless crystals repulsive astringent taste faint odor. D 1.59, mp 130-131C. Soluble in water, alcohol and acetone very slightly soluble in benzene. At temperatures shghtly higher than its melting point, it is converted partly to fumaric acid. Combustible. 

Catalysts also exhibit selectivity in their initial binding to reactants. Enzymes are well known for their ability to bind selectively to only one member of a pair of stereoisomers. The bound stereoisomer will undergo reaction, and the remaining isomer is inert to the reaction conditions. For example, the enantioselective addition of water to fumaric acid (the E isomer), which yields (.S )-malic acid (equation 9.7), is catalyzed by an enzyme called fumarase. Isomeric maleic acid (the Z isomer) fails to react in the presence of fumarase. 

---