Of fumaric acid

Racemic acid, ( )-tartaric acid, is a compound of the two active forms. M.p. 273 C (with IHjO), m.p. 205°C (anhydrous). Less soluble in water than (-t-)-tartaric acid. Formed, together with mesotartaric acid, by boiling (4-)-tartaric acid with 30% NaOH solution, or by oxidation of fumaric acid. Potassium hydrogen racemate is very insoluble. 

B. Conversion of maleic acid into fumaric acid. Dissolve 10 g. of maleic acid in 10 ml. of warm water, add 20 ml. of concentrated hydrochloric acid and reflux gently (provide the flask with a reflux condenser) for 30 minutes. Crystals of fumaric acid soon crystaUise out from the hot solution. Allow to cool, filter oflF the fumaric acid, and recrystallise it from hot. A -hydrochloric acid. The m.p. in a sealed capillary tube is 286-287°. 

A small quantity (ca. 3 g.) of fumaric acid may be recovered from the 6ltrate by heating it on a water bath with 15 ml. of concentrated hydrochloric acid, evaporating to about 150 ml., and then cooling with running water. The fumaric acid which separates is recrystallised from N-hydrochloric acid. 

The diethyl fumarate is readily prepared as follows. Reflux a mixture of 146 g. of fumaric acid (Section 111,143), 185 g. (236 ml.) of absolute ethanol, 450 ml. of boizene and 20 g. of concentrated sulphuric acid for 12 hours. Pour into a large volume of water, separate the benzene layer, wash successively with water, saturated lodium bicarbonate solution and water, dry with anhydrous magnesium sulphate, and remove the solvent on a steam bath. Distil the residue and collect the diethyl fumarate at 213-215° the yield is 150 g. 

Optically inactive starting materials can give optically active products only if they are treated with an optically active reagent or if the reaction is catalyzed by an optically active substance The best examples are found m biochemical processes Most bio chemical reactions are catalyzed by enzymes Enzymes are chiral and enantiomerically homogeneous they provide an asymmetric environment m which chemical reaction can take place Ordinarily enzyme catalyzed reactions occur with such a high level of stereo selectivity that one enantiomer of a substance is formed exclusively even when the sub strate is achiral The enzyme fumarase for example catalyzes hydration of the double bond of fumaric acid to malic acid m apples and other fruits Only the S enantiomer of malic acid is formed m this reaction... 

The reaction is reversible and its stereochemical requirements are so pronounced that neither the cis isomer of fumaric acid (maleic acid) nor the R enantiomer of malic acid can serve as a substrate for the fumarase catalyzed hydration-dehydration equilibrium... 

Hydration and Dehydration. Maleic anhydride is hydrolyzed to maleic acid with water at room temperature (68). Fumaric acid is obtained if the hydrolysis is performed at higher temperatures. Catalysts enhance formation of fumaric acid from maleic anhydride hydrolysis through maleic acid isomerization. 

Hydration of fumaric acid proceeds at high temperatures and pressures to give DL-malic acid [6915-15-7], HOOCCH2CHOHCOOH (25). 

Data for the production and sales of maleic anhydride and fumaric acid ia the United States between 1979 and 1992 are shown ia Table 5. Production of maleic anhydride during this time grew - 2% on average per year. Production of fumaric acid has declined during the same period as customers have switched to the less cosdy maleic anhydride when possible. All production of maleic anhydride in the United States in 1992 was from butane-based plants which used fixed-bed reactor technology as shown in Table 6. The number of fumaric acid producers has been reduced considerably since the early 1980s with only two producers left in the United States in 1992 as shown in Table 6. Pfizer shut down its fumaric acid plant at the end of 1993. However, Bartek of Canada will start up an expanded fumaric acid faciUty to supply the North American market for both their own and Huntsman s requirements. 

Albert Szent-Gynrgyi medicine, physiology discoveries ia connection with biological combustion processes, with special reference to vitamin C and catalysis of fumaric acid... 

Fumaric acid is converted to L-malic acid by hydration in the presence of the enzyme fumamse. From the structure of the substrate and the configuration of the product, it is apparent that the hydroxyl group has been added to the si fiice of one of the carbon atoms of the double bond. Each of the trigonal carbon atoms of an alkene has its fiice specified separately. The molecule of fumaric acid shown below is viewed fixjm the re-re fiice. 

Figure 6-18 shows a bell-shaped pH-rate profile for the hydrolysis of monomethyl dihydrogen phosphate. Other examples are the hydrolysis of o-carboxyphenyl hydrogen succinate and the hydration of fumaric acid. ... 

A solution of 3-dimethylsulfamoylphenthiazine (5 g) in anhydrous xylene (100 cc) is heated under reflux for 1 hour with sodamide (0.67 g). 3-(4-methyl-1-piperazinyl)-1 heated under reflux for 5 hours. After treatment of the reaction products, a crude oily base (2.5 g) is obtained after treatment. By the addition of a solution of fumaric acid in ethanol to an ethanolic solution of the base, 3-dimethylsulfamoyl-10-(3-4 -methyl-1 -piperazinylpropyD-phenthiazine diacid fumarate (2.6 g) is obtained, melting point 182°C. The base recrystallized from ethyl acetate melts at about 140°C. 

Fu marie Acid Ozonide. C4H407, a very expl compd, prepd by treating a soln of fumaric acid in methanol, cooled to —60°, with ozone Ref E. Briner D. Franck, Helv 21, 1297—1313 (1938) CA 33,535 (1939)... 

Fumaric acid is used as a flavoring, because it is the sourest tasting of the organic acids. Three parts of fumaric acid are as sour as five parts of citric acid. 

An important problem in emulsified organic-aqueous systems is that of scale-up, which is concerned with the realization of stable emulsions and the separation of phases after the reaction. The use of biphasic membrane systems that contain the enzyme and keep the two phases separated is likely to solve this problem. In the case of 5-naproxen an ee of 92% has been demonstrated without any decay in activity over a period of two weeks of continuous operation. A number of examples of biocatalytic membrane reactors have been provided by Giorno and Drioli (2000) and include the conversion of fumaric acid to L-aspartic acid, L-aspartic acid to L-alanine, and cortexolone to hydrocortisone and prednisolone. 

The enthalpy of decomposition of fumaric acid was determined experimentally -0.925 kJ/g. This value shows its unstable nature that is due to the second carboxyl group. 

For the diester of fumaric acid, EtAlCl2 was the most effective catalyst and the reaction proceeded with more than 90% diastereoselectivity.87... 

Many enzymes have absolute specificity for a substrate and will not attack the molecules with common structural features. The enzyme aspartase, found in many plants and bacteria, is such an enzyme [57], It catalyzes the formation of L-aspartate by reversible addition of ammonia to the double bond of fumaric acid. Aspartase, however, does not take part in the addition of ammonia to any other unsaturated acid requiring specific optical and geometrical characteristics. At the other end of the spectrum are enzymes which do not have specificity for a given substrate and act on many molecules with similar structural characteristics. A good example is the enzyme chymotrypsin, which catalyzes hydrolysis of many different peptides or polypeptides as well as amides and esters. 

Polyanhydrides based on unsaturated and fatty acid-derived monomers are shown in Table III. Poly(fumaric acid) (PFA) was fist synthesized by Domb et al. (1991) by both melt polycondensation and solution polymerization. The copolymer of fumaric acid and sebacic acid (P(FA-SA)) has been synthesized and characterized (Domb et al., 1991 Mathiowitz et al., 1990b). The mucoadhesive properties of this polymer... 

Hydrogen. The Synthesis and Oxidation of Fumaric Acid. J. Amer. chem. Soc. 64, 948 (1942). 

Arnstein, H. R. V., and R. Bentley Acid Oxidation of Fumaric Acid. 

Funke et al. [34] found that on thermal curing of unsaturated polyesters (UP) and styrene the conversion of fumaric acid units decreased with an increase in temperature. A following treatment of all samples at the highest curing temperature used before, had no effect on the conversion of the fumaric acid units. By a temperature increase at an early stage of the copolymerization reaction only the reaction rate could be increased,but the final conversion was the same as that obtained after a longer time at a lower temperature. 

Defects of the Krebs cycle. Fumarase deficiency was reported in children with mitochondrial encephalomyop-athy. Usually, there is developmental delay since early infancy, microcephaly, hypotonia and cerebral atrophy, with death in infancy or early childhood. The laboratory hallmark of the disease is the excretion of large amounts of fumaric acid and, to a lesser extent, succinic acid in the urine. The enzyme defect has been found in muscle, liver and cultured skin fibroblasts [16]. 

But similar oxidation of fumaric acid gives a raceime mixture... 

In addition to the reactions mentioned, ethyl diazoacetate takes part in many condensations with acetylene and ethylene derivatives, when the nitrogen is retained in the molecule. Thus, with esters of fumaric acid, for example, pyrazoline tricarboxylic esters are produced ... 

Carta, E. S. Soccol, C. R. Ramos, L. P. Fontana, J. D. Production of fumaric acid by fermentation of enzymic hydrolyzates derived from cassava bagasse, Bioresour. Technol, 1999, 68, 23-28. 

Figure 3.2b, The effect of pH on the initial rate of hydrogenation of fumaric acid (FA) catalyzed by [RhCl(TPPMS>3] in aqueous solution. [Rh]=5.2 x lO" M, [FA1=0.05 M, 60 C, Hi, 1 bar total pressure. The calculated distribution (a%) of nondissociated (H A) and dissociated (HA , fumaric acid is also shown. Reprinted with permission from Chem. Eur. J. 2001, 7, 193. Copyright (2001) Wiley-VCH Verlag GmbH.

On the other hand, the reaction of the oxazolidone derivative of fumaric acid and butadiene was found to proceed in poor enantioselectivity as compared with the reaction carried out in the presence of excess amounts of the chiral titanium reagent, and the cyclohexenedicarboxylic acid derivative was obtained in 32-45% ee. In order to achieve wide applicability for the catalytic procedure, the reaction conditions were... 

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