Methylsuccinic acid

The residue is cooled and dissolved in 171 ml. of nitric acid (sp. gr. 1.4) (Note 3), and the solution is warmed for 30 minutes on the steam bath. It is immediately concentrated to complete dryness under reduced pressure (Note 4). The flask is cooled, 300 ml. of benzene is added, and the mixture is refluxed for a short time to render the cake friable. The benzene is removed by decantation, and the cake is pulverized and extracted six times by refluxing it briefly with 300-ml. portions of ether. The combined benzene and ether extracts are filtered and concentrated to a volume of about 225 ml. In the meantime the residual salts are extracted twice by refluxing them vigorously for a short time with 300-ml. portions of benzene. The benzene solutions are separated by decantation and added to the ether concentrate. The distillation is then continued untO about two-thirds of the benzene has been removed, when the benzene solution is poured into a beaker and allowed to cool. The methylsuccinic acid is collected on a filter and is washed by shaking a suspension of it in 150 ml. of chloroform (Note 5). The yield of air-dried product, melting at 110-111 , amounts to 87-93 g. (66-70%) (Note 6). 

The residue must be dry because methylsuccinic acid is extremely soluble in water. 

Methylsuccinic acid has been prepared by the pyrolysis of tartaric acid from 1,2-dibromopropane or allyl halides by the action of potassium cyanide followed by hydrolysis by reduction of itaconic, citraconic, and mesaconic acids by hydrolysis of ketovalerolactonecarboxylic acid by decarboxylation of 1,1,2-propane tricarboxylic acid by oxidation of /3-methylcyclo-hexanone by fusion of gamboge with alkali by hydrog. nation and condensation of sodium lactate over nickel oxide from acetoacetic ester by successive alkylation with a methyl halide and a monohaloacetic ester by hydrolysis of oi-methyl-o -oxalosuccinic ester or a-methyl-a -acetosuccinic ester by action of hot, concentrated potassium hydroxide upon methyl-succinaldehyde dioxime from the ammonium salt of a-methyl-butyric acid by oxidation with. hydrogen peroxide from /9-methyllevulinic acid by oxidation with dilute nitric acid or hypobromite from /J-methyladipic acid and from the decomposition products of glyceric acid and pyruvic acid. The method described above is a modification of that of Higginbotham and Lapworth. ... 

Figure 4.2. Rotational-energy barriers as a function of substitution. Tbe small barrier ( 2kcal) in ethane (a) is lowered even further ( O.Skcal) if three bonds are tied back by replacing three hydrogen atoms of a methyl group by a triple-bonded carbon, as in methylacetylene (b). The barrier is raised 4.2 kcal) when methyl groups replace the smaller hydrogen atoms, as in neopentane (c). Dipole forces raise the barrier further ( 15 kcal) in methylsuccinic acid (d) (cf. Figure 4.3). Steric hindrance is responsible for the high barrier (> 15 kcal) in the diphenyl derivative (e). (After...

Figure 4.3. Energy versus bond rotation in methylsuccinic acid (schematic). The diagram shows the greater stability of staggered as compared with eclipsed forms, and the effect of size and dipole moment of substituents on the barriers. The slope of the curve at any point represents the force opposing rotation there. ( = energy of activation of rotation.) (After Gordon )...

D. Brownii, Rydb. From this speeies Manske prepared an alkaloida produet which could not be crystallised or converted into crystalline salts, but on alkaline hydrolysis yielded methylsuccinic acid (fine prisms, m.p. 112°), anthranilic acid and a crystalline base, m.p. 120-1°,... 

CggHjgOjN. HjO, m.p. 143°, [a] ° + 53-2° (EtOH), apparently identical with the basic hydrolytic product of lycaconitine (p. 686) from which methyllycaconitine differs in yielding methylsuccinic acid in place of succinic acid on hydrolysis. This established for the first time similarity in constitution between alkaloids of the two closely related Ranunculaceous... 

Methyl desoxyglycyrrhetate 61 Methyidigoxin 104 Methyl glycyrrhetate 61 Methyl iodide reagent 70 N-Methylphenylalanine 89 Methylsuccinic acid 249 Methyl sugars 188... 

Homer and Roder also found that dimethylmaleic acid 112, R = H) and its methyl ester 112, R = CH3) are reduced stereospecifically to meso-2,3-di-methylsuccinic acid and its methyl ester, respectively 113, R = H and CH3)ll7>. 

Heating the reaction for shorter periods gave erratic results. At this point the semisolid mixture can be diluted with 200 ml. of water, extracted with benzene, and the benzene extract fractionally distilled to give ethyl 2,3-dicyano-3-methylpentanoate, b.p. 146.0-147.5° (2.5 mm.), m27d 1.4429 (highly purified ester has b.p. 138.5-141.5° (2 mm.), 25d 1.4432). The overall yield of a-ethyl-a-methylsuccinic acid is decreased by about 5% when the dicyano intermediate is isolated. 

The sol-gel entrapment of the metal complexes [Ru(p-cymene)(BINAP)Cl]Cl and the rhodium complexes formed in situ from the reaction of [Rh(COD)Cl]2 with DlOP and BPPM has been reported by Avnir and coworkers [198]. The metal complexes were entrapped by two different methods the first involved addition of tetramethoxysilane to a THF solution of the metal complex and triethylamine, while the second method was a two-step process in which aqueous NH4OH was added to a solution of HCl, tetramethoxysilane and methanol at pH 1.96 followed by a THF solution of the appropriate metal complex. The gel obtained by each method was then dried, crushed, washed with boiling CH2CI2, sonicated in the same solvent and dried in vacuo at room temperature until constant weight was achieved. Hydrogenation of itaconic acid by these entrapped catalysts afforded near-quantitative yields of methylsuccinic acid with up to 78% e.e. In addition, the catalysts were found to be leach-proof in ethanol and other polar solvents, and could be recycled. 

Anodic oxidation of 1,2-dicarboxylic acids as their alkali metal salts in concentrated aqueous solution gives the alkene with the loss of two molecules of carbon dioxide [125]. Succinic acid affords etltene and methylsuccinic acid ptopene [50]. Allene is obtained from itaconic acid and the isomeric methylmaleic and methyl-fumaric acids give propyne... 

Methyl sorbate and analogous monomers were polymerized in the presence of (/ )-2-methylbutyllithium or of complexes between butyllithium and optically active Lewis bases (329, 330) (see formulas 32 and 33) the polymers show weak optical activity. The prevailing configuration of the — CH(CH3)— group was determined by the sign of rotation of the methylsuccinic acid obtained from the polymer after ozonization. The low optical purity ( = 6%) found is related to the presence of a remarkable stereochemical disorder (115, 116) and to the fact that the chiral agent is active, at least in the case of methylbutyllithium, only in the initiation reaction. 

Nonaka et al. 62) examined the asymmetric reduction of open-chain olefins in the presence of optically active amino acids. In the best case (R)-methylsuccinic acid (23) was formed in 2.4 % and 53 % optical and chemical yields, respectively, from citraconic acid (24) in the presence of (R)-cysteine. 

Methylthiophene has been prepared by the dry fusion of a salt of methylsuccinic acid and phosphorus trisulfide. 4 This reaction was later investigated quite completely in respect to ratio of reactants, rate of heating, carbon dioxide atmosphere, and dilution of reactants with sand.6 An excellent technical method for preparing methylthiophenes has been described which involves a vapor-phase reaction of preheated sulfur with pentanes.6 3-Methylthiophene has also been prepared by adding 50% crude isoprene (amylenes) to molten sulfur at 350°.7... 

IBG isobutyrylglydne, IVG isovalerylglycine, MW Molecular weight, MSA methylsuccinic acid,... 

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