Fumaric acid derivatives preparation

Pyrrolidines and pyrrolidinones can be synthesized on insoluble supports by intramolecular carbometallation of alkenes (Entry 1, Table 15.4) and by Ugi reaction of support-bound isonitriles with amines and 4-oxo acids (Entry 4, Table 15.4). In Entry 5 in Table 15.4, the pyrrolidinone ring is formed by intramolecular Diels-Alder reaction of a furan with a fumaric acid derivative. 2-Pyrrolidinones have also been prepared by treatment of resin-bound O-mesitylenesulfonyl cyclobutanone oximes with... 

Narasaka reported a highly enantioselective Diels-Alder reaction between isoprene and a fumaric acid derivative 17 using a catalytic amount of a chiral titanium reagent prepared from tartrate-derived chiral 1,4-diol 18 and TiCI2(0-/-Pr)2 [27]. When a stoichiometric amount of the partially resolved chiral diol (25% ee) was used, the corresponding cycloadduct 19 with 83% ee was obtained (Scheme 9.12). In this reaction, white precipitate was formed, which proved to... 

To a suspension of 150 mg of 4 A molecular sieves in 3 mL of toluene, 10 mL of a toluene solution of about 0.07 mmol of the chiral titanium catalyst (prepared by the procedure above) are added and the mixture is cooled to OX. 0.7 mmol of the fumaric acid derivative 1 in 4mL of toluene is added to the mixture, and then 5 mL of hexane and 1 mL of isoprene (3, R1 = CH3) are added. The mixture is stirred overnight at 0 X. pH 7 phosphate buffer is added, and the mixture is worked up as above. 

Unlike lactic acid, mandelic acid (7) occurs in nature only in small amounts and is therefore more expensive. Formerly, it was obtained by resolution of the racemate with a chiral base, such as l-phenylethylamines or ephedrine6, but enantioselective reductions of a-oxo-a-phenylacetic acid by chemical or biochemical methods have become feasible (Section D.2.3.I.). Esters of mandelic acid, e.g.. 8. can be prepared by any convenient esterification technique (see. for example, refs 7 and 46) and have been used for enantioselective protonation reactions (Sections C. and D.2.I.). Similar to the corresponding lactic esters, fumaric acid derivatives 9 are obtained from the mandelic esters and used as chiral dienophiles in diastereoselective Diels Alder reactions (Section D. 1.6.1.1.1.2.2.1.). 

Heating benzoyl azide with ethanol or benzoylhydrazine gave the corresponding urethane (5) or benzoylphenyl semicarbazide (6), respectively. The explosive diacyl azide 8, prepared from fumaric acid-derived 7, underwent double rearrangement in ethanol to the dicarbamate 9. ... 

Arylhydrazines, reaction with MA, 85, 86 Arylhydrazones, reaction with MA, 83 Arylthiosuccinic anhydrides, melting points, 50 Ascaridol, 466 Aspartic acid, 47, 48 synthesis from fumaric acid, 47 Aspartic acid derivatives, preparation with oxizime-MA reaction, 228... 

Technosphere Insulin (TI) inhalation powder is prepared from fumaryl diketopiperazine (FDKP), a diketopiperazine derived from lysine and functionalized with fumaric acid groups on each side arm of the molecule (Fig. 2). 

German name, Trauben-saure, is derived from the word for grapes. It is probable that it does not exist in grapes as racemic acid but that it is formed from the dextro acid as this transformation can easily be effected by the action of acids or even by water alone. When tartaric acid is prepared synthetically from succinic acid, from glyoxal, or from malic, maleic or fumaric acids either racemic acid or meso-tartaric acid is always formed. That is, synthetic reactions result in the formation of an inactive form. The methods of splitting racemic acid into its optically active components has been fully discussed. The sodium-ammonium racemate is the only salt that is of importance. This has been spoken of in connection with the method of splitting racemic acid into its components.. Like the free acid this salt exists, in dilute solution, as equal molecular parts of the dextro and levo forms. Only in concentrated solution does it exist as the racemate itself. 

As is shown in Scheme 6 and Table 1, alkynyl sulfides can be employed in the asymmetric [2-1-2] cycloaddition reaction however, the reactivity of alkynyl sulfides is largely dependent on the substituent at sulfur. A phenyl sulfide, 1-phenylthio-l-hexyne (5e), does not react with 2a, while the alkynyl methyl sulfides 5a-d react smoothly with fumaric and acryUc acid derivatives 2a,c, yielding cyclobutenes 6. Trisubstituted cyclobutenes are prepared in good yield and in almost enantiomerically pure forms with only a catalytic amount of the chiral titanium reagent. For the preparation of tetrasubstituted cyclobutenes, however, an equimolar amount of the chiral titanium is required for the reaction to go to completion. Compared with the ketene dimethyldithioacetal 3a, alkynyl methyl sulfides 5 are less reactive and the reaction between the crotonoyloxazo-lidinone 2b and 5 fails even in the presence of an equimolar amount of the catalyst. 

Thus far, EMRs have been successfully used with macromolecular substrates, as for the saccharification of cellulose11-13 15 26 and protein hydrolysis,19 or with low molecular weight substrates, as for cellobiose hydrolysis9 and L-malic acid production from fumaric acid.20 Bench and large scale plants are already in operation for the preparation of N-acetyl-D,L derivatives from L-amino acids by means of acylase and the production of L-malic acid from fumaric acid by means of fumarase.20 In the case of fumarase, conversions of up to 86% with resolution rates of up to 85% have been attained. 

Two acids are known to which these formulas are assigned. The cis form (formula 1) is given to maleic acid, and the trans form (formula 2) to fumaric acid. The two acids differ markedly in physical properties. Fumaric acid, which occurs somewhat widely distributed in plants, does not melt, but sublimes at about 200°. It is difficultly soluble in water. Maleic acid melts at 130°, is readily soluble in water and is a much stronger acid than fumaric acid (344). Both acids can be prepared by heating malic acid, which is a hydroxyl derivative of succinic acid. If the temperature is kept at between 130° and 150° fumaric acid is obtained when the acid is distilled, the chief product is the anhydride of maleic acid, which is readily converted into the acid by water. The reaction by which fumaric acid is obtained is represented by the equation,—... 

A large number of dibasic acids and anhydrides are used in the preparation of poly(ester amide)s. These include terephthalic acid, phthalic anhydride, isophthalic acid, endic endo-cis bicyclo(2,2,10-5)-heptene-2,3-dicarboxylic] anhydride, hydrogenated endic anhydride, maleic anhydride, fumaric acid, dichloromaleic anhydride, itaconic acid, brassylic acid, dimer acid, adipic acid, sebacic acid, succinic acid, trimeUitic anhydride, pyrromellitic anhydride and ethylenediamine tetraacetic acid (EDTA). However, tri- and poly-functional compounds are used only partially and are combined with bifunctional derivatives, or derivatives of previously prepared multifunctional compounds which are subsequently polymerised with bifunctional compounds. 

The Diels-Alder adduct between levopimaric acid and maleic anhydride, maleopimaric anhydride (Fig. 4.8) and the corresponding diacid are certainly the most important derivatives of this family mainly because of their applications in various domains. Levopimaric acid has also been used in the preparation of other adducts with a wide variety of dienophiles such as fumaric acid, acrylonitrile, acrylic acid, vinyl acetate and tetracyanoethylene [5]. 

Recently, the possible preparation of different stereoisomers by preparative electroreduction at a controlled potential and pH was derived from polarographic data. Thus for a, a -dibromosuccinic acids, the erythro-form of the free add and of its anions is reduced to fumaric acid. On the other hand, the threo-epimer is reduced to the fumaric acid only in an undissodated 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 dibromosuccinic acid are reduced only to the dialkyl ester of fumaric acid—similarly to the undissodated free adds. ... 

Glovsky et al. observed an anticomplementary activity for levopimaric acid (45), a derivative of abietic acid, and prepared a number of synthetic derivatives such as maleopimaric acid (46) and fumaropimaric acid (47), being Diels-Alder substitution products of levopimaric acid v ith maleic anhydride or fumaric acid, respectively [28, 29]. Maleic acid is cis-butenedioic acid, fumaric acid is trans-butenedioic acid. Maleopimaric acid inhibited complement-mediated haemolysis via classical path-way activation (45% inhibition at a concentration of 500 iM), Fumaropimaic acid inhibited in vivo complement-dependent systemic Frossman, cutaneous Frossman, and reverse passive Arthus reactions. These pimaric acid derivatives have already been included in earlier reviews on complement-active compounds [8, 30]. The... 

Fumaric acid can be similarly treated but it reacts less readily than maleic acid. Sulfosuccinate can also be prepared by nucleophilic displacement on bromo or chlorosuccinic acid. However, the ease of addition across the maleic derivatives has made direct addition the method of choice. 

Diester derivatives of maleic and fumaric acid (see Chapter 3) are not easily polymerized. However, they do yield soft, tacky thermoplastics with free-radical generating initiators such as BPO. Diethyl fumarate, for example, polymerizes to an 89% yield of poly (ethyl succinate) when heated in the presence of 2% BPO for 7 Liquid-phase (neat) reaction at high pressure (5000 psi) improves the yield.Polymers of higher softening point and higher molecular weight may be prepared by emulsion-polymerization techniques. 

Ester and ester derivative polymers are biodegradable polymers, and there are a large number of biodegradable hydrogels made of ester prepolymers by cross-linking with monomers such as AM and VP. The ester prepolymers are prepared via condensation reactions between an unsaturated diacid like fumaric acid, itaconic acid, or allylmalonic acid and a diol such as low molecular weight PEG. 

Chromium(II) sulfate is a versatile reagent for the mild reduction of a variety of bonds. Thus aqueous dimethylformamide solutions of this reagent at room temperature couple benzylic halides, reduce aliphatic monohalides to alkanes, convert vicinal dihalides to olefins, convert geminal halides to carben-oids, reduce acetylenes to /raw5-olefins, and reduce a,j3-unsatu-rated esters, acids, and nitriles to the corresponding saturated derivatives. These conditions also reduce aldehydes to alcohols. The reduction of diethyl fumarate described in this preparation illustrates the mildness of the reaction conditions for the reduction of acetylenes and o ,j8-unsaturated esters, acids, and nitriles. 

---