Fumaric acid Synthesis

Friedel-Crafts synthesis TALEIC ANHYDRIDE, MALEIC ACID AND FUMARIC ACID] (Vol 15)... 

Commercial Synthesis ofR,S-Mahc Acid. The commercial synthesis of R%-mahc acid involves hydration of maleic acid [110-16-7] or fumaric acid [110-17-8] at elevated temperature and pressure. A Japanese patent (33) describing a manufacturing procedure for malic acid claims the direct hydration of maleic acid at 180°C and 1.03—1.21 MPa (150—175 psi). 

Oxidation of n-hutane to maleic anhydride is becoming a major source for this important chemical. Maleic anhydride could also be produced by the catalytic oxidation of n-butenes (Chapter 9) and benzene (Chapter 10). The principal use of maleic anhydride is in the synthesis of unsaturated polyester resins. These resins are used to fabricate glass-fiber reinforced materials. Other uses include fumaric acid, alkyd resins, and pesticides. Maleic acid esters are important plasticizers and lubricants. Maleic anhydride could also be a precursor for 1,4-butanediol (Chapter 9). 

Figure A8.13 Two step enzymatic synthesis of L-alanine from fumaric acid.

The synthesis of highly substituted rigid tricyclic nitrogen heterocycles via a tandem four-component condensation (the Ugi reaction)/intramolecular Diels-Alder reaction was investigated in both solution and solid phase [24]. The Ugi reaction in MeOH (Scheme 4.2) involves the condensation of furylaldehydes 17, benzylamine 18, benzyl isocyanide 19 and maleic or fumaric acid derivatives 20, and provides the triene 21 which immediately undergoes an intramolecular Diels-Alder reaction, affording the cycloadduct 22 in a diastereoisomeric mixture with high yield. 

Figure 4.22 Slurry reactor synthesis of malic acid from fumaric acid applying a batch process followed by precipitation and crystallization...

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

An attempted synthesis of biotin using thiocarbonyl ylide cycloaddition was carried out (131,133,134). The crucial step involves the formation of the tetrahydrothiophene ring by [3 + 2] cycloaddition of a properly substituted thiocarbonyl ylide with a maleic or fumaric acid derivative (Scheme 5.27). As precursors of the thiocarbonyl ylides, compounds 25a, 72, and 73 were used. Further conversion of cycloadducts 74 into biotin (75) required several additional steps including a Curtius rearrangement to replace the carboxylic groups at C(3) and C(4) by amino moieties. 

One of these units is converted into a derivative A so that an enantiomeric mixture is generated which can be resolved in the usual manner. The desired enantiomer is used for the continuation of the synthesis, whereas the undesired one is recycled to the starting meso-compound. An illustration of this method is the synthesis of (/-biotin (9) from fumaric acid via the meso-intermediates 5/6 and the enantiomers 7/8 50. 

By far, the best asymmetric synthesis is done in nature by enzymes7). These have also found industrial application8, e.g. the stereospecific amination of fumaric acid (10) to (S)-aspartic acid (11) ... 

Any reaction in which only one of a set of stereoisomers is formed exclusively or predominantly is called a stereoselective synthesis.184 The same term is used when a mixture of two or more stereoisomers is exclusively or predominantly formed at the expense of other stereoisomers. In a stereospecific reaction, a given isomer leads to one product while another stereoisomer leads to the opposite product. All stereospecific reactions are necessarily stereoselective, but the converse is not true. These terms are best illustrated by examples. Thus, if maleic acid treated with bromine gives the dl pair of 2,3-dibromosuccinic acid while fumaric acid gives the meso isomer (this is the case), the reaction is stereospecific as well as stereoselective because two opposite isomers give two opposite isomers ... 

Reduction -of benzene [BENZENE] (Vol 4) -dehydrogenase-catalyzed [ENZYMES IN ORGANIC SYNTHESIS] (Vol 9) -m dyes manufacture pYES AND DYE INTERMEDIATES] (Vol 8) -of esters pSTERS, ORGANIC] (Vol 9) -maleic anhydride [MALEIC ANHYDRIDE, MALEIC ACID AND FUMARIC ACID] (Vol 15) -microbial transformations [MICROBIAL TRANSFORMATIONS] (Vol 16) -of mtrophenols [AMINOPHENOLS] (Vol 2) -of terphenyls [BIPHENYL AND TERPHENYLS] (Vol 4)... 

Biotin can be produced commercially by using, for starting the synthesis, meso-diamino succinic acid derivative of fumaric acid. 

The commercial synthesis offl.S-malic acid involves hydration of maleic acid or fumaric acid at elevated temperature and pressure. 

Maleic and phthalic anhydrides and fumaric acid are mainly used for polyester resin synthesis. However, dihydric alcohols such as ethylene and propylene glycols, diethylene, dipropylene, triethylene and neopentyl glycols, and hydrided or oxypropylened diphenylolpropane are also used.5 7 Different combinations of dibasic acids with diols allow us to vary the composition and properties of the resulting polyester resins over a wide range. 

Figure 2.3 Cloud point curves of diethanediol-based polyester oligomers (Mn 1 kg mol-1), dissolved in styrene the diacids used for polyester synthesis were (a) fumaric acid, (b) blend of isophthalic and fumaric acid, and (c) isophthalic acid.

Fumaric acid is a naturally occurring sour-tasting compound found in many plants such as Fumaria officinalis L. (Fumariaceae), Boletus scaber Bull. (Boletaceae), and Fames igniaries (Fries) Kickx. (Pluporaceae). It is an essential component for respiration in plant and animal tissues. It is produced by fermentation with mold, such as Rhizopus nigricans, or by chemical synthesis. It is also used in soft drinks and ice cream and as an acidulant along with citric acid. 

Photochemical reaction of bifunctional ketoenamines in CC14 with maleic and fumaric acids and esters can be used for stereoselective synthesis of cis and trans alkyl 7-azabicyclo[2.2.1]heptanecarboxylates in good yield330 (equation 248). 

Akhtar M, Botting NP, Cohen MA Gani D (1987) Enantiospecific Synthesis of 3-Substituted Aspartic Acids via Enzymic Amination of Substituted Fumaric Acids. Tetrahedron 43 5899... 

Some alternative syntheses use malic acid, urea, and PPA (61 SCI 1923) or maleic/fumaric acid, urea, and polyphosphonic acid (PPA) (71S154). The reaction of formylacetate with thiourea is convenient for the synthesis of 2-thiouracil (08JA547 10JA19). Another main synthesis involves the... 

Until now, examples were discussed in which amino acids are produced from mixed organic matter substrates. It is also possible to start with defined chemical compounds. An example is the synthesis of L-alanine from fumaric acid in a two-step reaction. Other examples for a highly selective fermentation are the synthesis of L-Dopa from orthocatechol and of L-tyrosine from phenol. 

Friedel-Crafts, acylation, 307 alkylation, 212 synthesis, 207, 219 Fries rearrangement, 435 F-strain, 456 Fumaric acid, 338 Functional groups, 6 ... 

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