Methyl fumarate, preparation

The enzyme aconitase catalyzes the isomerization of citric acid to isocitric acid via the intermediate cis-aconitic acid (Scheme 46), and various attempts have been made to model this reaction. The cobalt Ill) complexes derived from methyl maleate (171) and methyl fumarate (172) have been prepared to study intramolecular attack by coordinated hydroxide on the alkene. Generation of the hydroxo species of the maleic acid complex leads to rapid cyclization to give the... 

Fig. 3.1 Chromatogram of extracted acids as their methyl esters prepared using boron trifluoride/methanol separated on a 3 m (0.0025 m i.d.) stainless-steel column packed with 5 per cent di(ethylene glycol) adipate on Chromosorb W (AW, DMCS, 100-120 mesh) using temperature programming from 60°C to 185°C at 7°C min, with an initial isothermal delay of 6 min and a final delay at 185°C until elution of trimethyl citrate. Peak identifications are 1, position of methyl pyruvate 2, methyl lactate 3, methyl-2,2-dimethoxypropionate 4, dimethyl fumarate 5, dimethyl succinate 6, methyl laurate (internal standard) 7, dimethyl malate 8, trimethyl citrate. (Redrawn with modifications from Hautala and Weaver, 1969)...

With an activated C—C triple bond two successive additions can occur if the intermediate alkene is reactive enough. DMAD and 3,5-dimethylpyrazole give an initiaj fumarate (255) which reacts further at the other end to form regioselectively the succinates (256). On the other hand, methyl ethynyl ketone reacts twice at the same carbon atom with pyrazole to form 1,1-pyrazolylbutanone (258) (68ZC458). The probable intermediate, a pyrazolide vinylogue (257), can be prepared from methyl chlorovinyl ketone and pyrazole, in a reaction which is similar to acetylation (Section 4.04.2.1.3(x)). 

Huisgen et al.165 prepared the methyl pyrido[l,2-u]pyrimidine-2-carboxylate (100) from tetrazolo[5,l-u]pyridine and dimethyl maleate or fumarate at 160 C. The reaction presumably proceeds via the intermediates (97-99). Compound 100 was also obtained from 2-aminopyridine and dimethyl acetylenedicarboxylate. 

Methyl-l-piperazinyl)benzimididazole (5.00 g) prepared as above is dissolved in N,N-dimethylformamide (50 ml) and thereto is added sodium hydride (concentration 50%) (1.50 g) at room temperature, and the mixture is stirred for 30 minutes. To the mixture is added 2-bromoethyl ethyl ether (4.00 g), and the mixture is stirred at 70°C for 10 hours. To the reaction mixture is added water (150 ml), and the mixture is extracted with ethyl acetate. The extract is washed with water, dried over anhydrous magnesium sulfate and then concentrated to give a brown oily substance (5.40 g). The brown oily substance is treated with fumaric acid (3.26 g) in hot ethanol. The crude crystals thus obtained are recrystallized from ethyl acetate-ethanol to give l-[2-(ethoxy)ethyl]-2-(4-methyl-l-piperazinyl)benzimidazole 3/2 fumarate (6.31 g) as colorless plates, melting point 167.5°-168.5°C. Elementary analysis for C22H30N4O7 Calcd. (%) C, 57.13 H, 6.54 N, 12.11 Found (%) C, 57.04 H, 6.44 N, 12.02. 

Preparation of 2-(6-methoxy-3-methyl-indazol-l-yl)-l-methylethylamine fumarate... 

Condensations of chloroacetyl chloride (and similar compounds) with substituted ethylenediamines to give 1,4-disubstituted piperazin-2-ones have been described, and a number of 4-alkyl(or aralkyl)- -arylpiperazin-2-ones has been prepared either by catalytic debenzylation or pyrolytic debenzylation (or demethylation) of I,l-dialkyl(or l,l-diaralkyl)-3-oxo-4-arylpiperazinium halides (1609). 3-Ethoxy-carbonylmethylene-6-methylpiperazin-2-one has been synthesized by the reaction of diethyl acetylenedicarboxylate with propylenediamine (1610), and treatment of diethyl fumarate with propylenediamine has been shown to give 3-ethoxycarbonyl-methyl-6-methylpiperazin-2-one, also prepared from the diethyl ester of N- 2 -hydroxyiminopropyl)aspartic acid (84) (1611). 

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. 

The experimental procedure described here for the preparation of Ru(ti -methyl acrylate)(C0)4 is applicable to a variety of other olefins as manifested by the syntheses of Ru(Ti -olefin)(CO)4 complexes of, for example, dimethyl fumarate, dimethyl maleate, allyl acrylate, methyl vinyl ketone (3-butene-2-one), and acrylonitrile. ... 

Shea and co-workers (109,110) were the first to try this approach. They prepared polymers from the optically active (-)-trans-l,2-cyclobutanedicarboxylic diester 15 and obtained cavities after splitting off the template containing two benzyl alcohols each. To these cavities fumaric acid could be bound. It was reacted with a methylene-transfer reagent [(dimethylamino)methyl-phenyl-oxosulfonium tetrafluoroborate]. The cyclopropanedicarb-... 

In some cases, dicarboxylic acid monomers, which cannot be homopolymer-ized, like itaconic acid (lA) or fumaric acid, may be employed in a formulation. When incorporated into the latex particle, they offer the advantage of introducing two carboxyl groups per molecule of monomer (i.e., increasing the carboxyl loading) for enhanced colloidal stability or to increase the number of reactive sites available. For example. Lock et al. recently [23] studied the role which itaconic acid played in the nucleation of latex particles prepared via the emulsion copolymerization of n-butyl acrylate and methyl acrylate. 

Proteoliposomes containing polysulfide reductase and either hydrogenase or formate dehydrogenase isolated from W. succinogenes do not catalyze polysulfide sulfur respiration unless 8-methyl-menaquinone is present (Table 3). Menaquinone with a side chain consisting of six or four isoprene units, or vitamin Ki served in reconstituting fumarate respiration, but did not replace 8-methyl-menaquinone in polysulfide sulfur respiration. The low activities of polysulfide sulfur respiration observed without added 8-methyl-menaquinone were probably due to the small amounts of this quinone associated with the enzyme preparations used. Maximum activity of polysulfide sulfur respiration required 10 p.mol 8-methyl-menaquinone per gram phospholipid [O. Klimmek and W. Dietrich, unpublished results]. 

Ethoxy-4-methyloxaole has been used to form pyridoxine (MI-286, R = H). With maleic anhydride it gives an adduct that, on treatment with ethanolic hydrogen chloride, forms the products W-287 and XII-288 (R = R - Et) and a monoester (XII-288 R = Et, R = H or R = H, R = Et). The diethyl ester MI-288 is also formed from ethyl maleate or ethyl fumarate and 5-ethoxy-4-methyloxazole. Fumaronitrile and ethoxy-4inethyloxazol ve 4,5-dicyano-2-methyl-3-pyridinol, ° also a known precursor to pyridoxine. 5-Ethoxy 4-irethyloxaolesand 2-butene-1,4-diol give pyridoxine (XII-286, R = H), which is difficult to purify when prepared in this way (assay, 23%). 

Methacrolein dimethylhydrazone adds to acrylic derivatives (ester, nitrile, methyl vinyl ketone) in the absence of solvent, under sonication with pulsed irradiation (Eq. 13).Compounds inaccessible conventionally were prepared in good yields. Direct comparison with thermal conditions is not feasible since the latter were made in solution. From maleic and fumaric esters, the same trans diester forms in 99% yield by sonication for 48 h at 50°C (Eq. 14). The absence of stereospecificity is an argument frequently invoked against a concerted mechanism. With these substrates, relatively long irradiation times are required. 

Preparative Method prepared by the addition of methyl isothiocyanate to acetylenedicarboxylic acid (ethanol, 25 °C) to afford a 6 1 mixture of 2-(methylthio)fumaric and -maleic acids, which are dehydrated by dissolution in thionyl chloride for 1 h at 25 °C, then 7 h at 60 °C. Excess SOCI2 is removed at 120 °C at aspirator pressure, followed by distillation of the residue to afford the crystalline anhydride in 68-77% yield. ... 

Methyl methacrylate-2-ethylhexyl acrylate-MA terpolymers, in the compositional range 40-50 42-52 8, have been prepared in naptha at 130-140 C to obtain coating resins/ Postreaction of the materials with trimethylol-propane, which introduced both hydroxyl and carboxyl sites on the terpolymer backbone, provided reactive moieties for amino-resin crosslinkers. Unsaturated monohydroxy dialkyl maleates and fumarates, such as 2-hydroxyethyl isobutyl fumarate, have also been copolymerized with various acrylate-methacrylate combinations to obtain low-viscosity, heat-hardening, filmforming copolymers.These copolymers may also be crosslinked with amino resins to provide valuable protective coating. 

Tetrahydro-2-furylsuccinic anhydride, MA-tetrahydrofuran adduct, 203 Tetrahydro-2-methyIfuran, MA radical adduct, 203 (Tetrahydro-2-methyl-2-furyl)succinic anhydride, MA-tetrahydro-2-methylfuran adduct, 203 Tetrahydronaphthalene, MA radical adduct, 198 l-(Tetrahydronaphthyl)succinic anhydride, MA-tetrahydronaphthlene adduct, 198 1,1,2,2-Tetrahydroperfluoroalkyl fumarate, grafting on polyethylene, 462 Tetrahydrophthalic anhydride MA copolymerization, 586 preparation, 15... 

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