Glutaric acid 3-ETHYL-3-METHYL

P-ETHYL-p-METHYLGLUTARIC ACID (Glutaric acid, 3-ethyl-3-methyl-)... 

This synthesis has one rather anomalous application, when a-bromo-isobutyric acid (or its ethyl ester) is heated with silver, some tetramethyl-succinic acid is produced in the ordinary way (B., 23, 297 26, 1458). But there also appears trimethylglutaric acid (A., 292, 220). To explain the unexpected formation of this acid, it has been assumed that a portion of the a-bromoisobutyric acid gives up HBr to form methylacrylic acid. This latter then forms j3-bromoisobutyric acid, and the silver withdraws bromine from the a- and /3 acids, whereby the residues unite to tri-methyl-glutaric acid (B., 22, 48, 60). A similar explanation applies to some other syntheses in which tetramethylsuccinic and trimethylglutaric acids appear together. 

Glutaric acid, 30, 48 i8, 8-dimethyl-, 31, 40 3-ETHYL-3-METHYL-, 36, 28 Glutaric anhydride, ck-phenyl, 30, 81 Glycerol, 32, 72... 

Kompa s Synthesis of Camphoric Acid.— The synthesis of camphoric acid is accomplished by starting with di-ethyl oxalate and condensing it with the di-ethyl ester of di-methyl glutaric acid. 

It is interesting to note that in fermented products the same alcohols always form, even if different sources of nitrogen, but not singular aminoacids, are available. Ketoacids can also be directly reduced to hydroxyacids such as lactic, 2-hydroxy-3-methyl butyric, 2-hydroxy-3-methyl pentanoic, 2-hydroxy-4-methyl pentanoic, 2-hydroxy-3-phenyl propionic and 2-hydroxy glutaric acids. The corresponding ethyl esters can dramatically influence the wine aroma. 

A. N. Dey (174) has described an independent synthesis of the alkaloids. Michael condensation of ethyl 7-ethoxy- or 7-phenoxy-crotonate (LI, R = OEt, R = Et or Ph) with ethyl malonate or cyan-acetate, followed by ethylation and hydrolysis, furnished a mixture of the two racemic forms of the glutaric acid, LII, which were separated by virtue of their different ease of anhydride formation. On treatment with hydrobromic acid, they gave rise to dl-homopilopic acid and dl-homo-isopilopic acid (LIII, R = OH), respectively. Corresponding methyl ketones (LIII, R = Me) were obtained by a similar synthesis from... 

The Michael reaction of nitriles with unsaturated carbonyl compounds was examined using the SA-NEtj catalyst As shown in Table 1.6, the SA-NEtj showed the highest catalytic activity for the Michael reaction of ethyl 2-cyanopropionate with ethyl acrylate to afibrd 2-cyano-2-methyl glutaric acid diethyl ester in 94% yield (entry 1). SiOj-NEtj was much less active under the reaction conditions (entry 2). Neither triethylamine nor sihca-alumina promoted the desired addition reaction (entries 3 and 4). Notably, the reaction scarcely proceeded with the... 

Extension by three carbon atoms is possible with methyl glutarate [183], by the isoprene unit with ethyl 3-methyl adipate [184], by four carbon atoms with methyl adipate [143], by five carbon atoms with methyl pimelate [185] and by six carbon atoms with methyl suberate [186]. A series of branched -fluorocarboxylic acids were prepared by cross-coupling with oo-fluorocarboxylic acids [187]. For further examples see Tables 6, 7. 

The permeability and water uptake of Eudragit RS or RL [chemical name, poly(ethyl acrylate, methyl methacrylate, trimethylammonioethyl methacrylate chloride)], can be influenced by the presence of different counterions in the release medium.It was found that theophylline was released faster from Eudragit RS-coated pellets, when succinic, acetic, glutaric, tartaric, malic, or citric acid are present in the release medium. Increased permeability was explained by the higher hydration of the film, also expressed as the free volume. ... 

Crossed coupling has also been applied to the extension of the carbon chain in fatty acids. Extension by two carbon atoms is achieved with succinate half esters,whereby separation problems can be simplified by using the benzyl half ester.Expansion by the propane unit has been accomplished with methyl glutarate, ° by the isoprene unit with ethyl 3-methyladipate, by four carbons with methyl adipate, by the pentane unit with methyl pimelate, and by six carbon atoms with methyl suberate. 

In the second step, the olefmic ester is sent to another reactor with a new quantity of carbon monoxide and methanol. The operation takes place at high temperature, 185°C, hut at lower pressure (3. IQ6 Pa absolute). Methyl adipate is formed with a molar yield of 75 per cent Methyl glutarate and methyl ethyl succinate are also formed. After purification by distillation, the methyl adipate is hydrolysed to adipic acid. 

This second step yields about 85% of the dimethyl adipate. The main by-products are about 10% dimethyl methyl glutarate, 3% dimethyl ethyl succinate, 1% dimethyl diethyl succinate, and 1% methyl pentanoates. The dimethyl adipate is isolated by distillation and converted to adipic acid by hydrolysis. 

Cyclic j -diketones from ketocarboxylic acid esters. Diethyl a-methyl-a-acetyl-glutarate in dry ether added dropwise with stirring to a suspension of alcohol-free K-ferf-butoxide in dry ether, and refluxed 3 hrs. -> ethyl l-methyl-2,4-dioxocyclohexane-l-carboxylate. Y 70.4%. S. M. Mukherji, R. K. Sharma, and O. P. Vig, Soc. 1958, 4770. 

The main starting material for the majority of syntheses of these compounds is )S-(m-anisyl)ethyl bromide (78), obtained in ten stages from m-aminophenol with an over-all yield of 22% [209]. The successive condensation of the bromide (78) with sodiomalonic ester and the chloride of glutaric semiester led to the keto triester (79), which by cyclization, saponification, and methylation was converted into the bicyclic diester (80) [188, 209]. In another variant, the bromide (78) was condensed with the diester of p -oxo-pimelic acid to form the keto diester (73) from which the diester (80) was again obtained by cyclization, hydrolysis, and methylation [210]. 

Fig. 7.2 Chromatogram of acidic metabolites extracted from the urine of a normal child using DEAE-Sephadex and re-extraction with solvents after ethoxime formation and freeze-drying by reconstitution in water, acidification with hydrochloric acid, saturation with sodium chloride, and solvent extraction with diethyl ether (three times) and ethyl acetate (three times), evaporation of the solvents from the combined extracts using dry nitrogen and trimethylsilylation using the minimum quantity of BSTFA. Separated on 10 per cent OV-101 on HP Chromosorb W (80-100 mesh) by temperature programming from 110°C to 285°C at 4°C min with an initial 5 min isothermal delay. Peak identifications are 1, phenol plus lactate 2, glycollate 3, cresol 4, 3-hydroxyisovalerate 5, benzoate 6, phosphate 7, succinate 8, 3-methyladipate 9, 3-hydroxy-3-methyl-glutarate 10, 4-hydroxyphenylacetate 11, homovanillate plus some aconitate 12, hippurate 13, citrate 14, vanilmandelate 15, n-tetracosane (standard) 16, n-hexacosane (standard).

Fig. 10.19 Chromatogram of organic acids extracted using ethyl acetate from the urine of a patient with 3-hydroxy-3-methylglutaric aciduria and separated as their trimethylsilyl derivatives on 5 per cent SE 52 on Chromosorb W (AW-DMCS, 100-120 mesh) using temperature programming from 75°C to 220°C at 2°C min with initial and final isothermal delays of 10 min. Peak identifications are 1, 3-hydroxyisovalerate 2, hydroxycaproate isomer 3, glutarate 4, 3-methylglutarate 5 and 6, 3-methyl-glutaconate peaks 7, adipate 8, 4-phenylbutyrate (internal standard) 9, 3-hydroxy-3-methylglutarate 10, ascorbate. (Redrawn with modifications from Duran ct. a/., 1978)...

Fig. 11.2 Total ion current chromatogram (Varian MAT 44 GC-MS) of organic acids extracted using ethyl acetate and diethyl ether from the urine of a patient with propionic acidaemia and separated as their trimethylsilyl derivatives on a 25 m SE-54 WCOT capillary column using temperature programming from 70°C to 220°C at 4 C min Peak identifications are 1, lactate 2, 3-hydroxypropionate 3, 3-hydroxybutyrate 4, 2-methyl-3-hydroxybutyrate 5, 3-hydroxyisovalerate 6, 3-hydroxy- -valerate 7, aceto-acetate 8 and 9, 2-methyl-3-hydroxyvalerate 10, 3-oxovalerate 11, 2-methyl-3-oxo-valerate (isomer 1) 12,2-methylacetoacetate 13,2-methyl-3-oxovalerate (isomer 2) 14 propionylglycine 15, glutarate 16, adipate 17, 5-hydroxymethyl-2-furoate 18, 2-hydroxyglutarate 19,3-hydroxy-3-methylglutarate 20,4-hydroxyphenylacetate 21 and 22, methylcitrate 23,4-hydroxyphenyl-lactate 24, palmitate. (Redrawn with modifications from Truscott et al., 1979)...

Fig. 14.7 Chromatogram of organic acids extracted using ethyl acetate and diethyl ether from the urine of a child with Jamaican vomiting sickness, separated as their methyl derivatives (diazomethane) on 5 per cent OV-1 using temperature programming from 70°C to 300°C at 4°C min with a 4 min initial isothermal delay. Peak identifications are 1, 3-hydroxybutyrate plus 3-hydroxyisovalerate (approx. 4 6) 2, ethylmalonate 3, methylsuccinate 4, octanoate 5, glutarate 6, adipate 7, isovalerylglycine 8, 4-octenedioate plus furandicarboxylate 9, suberate (octanedioate) 10, /i-hexanoyl-glycine 11, decenedioate 12, sebacate (decanedioate) 13, hippurate 14, n-pentadecanoate (internal standard) 15, palmitate 16, stearate. (Redrawn with modifications from Tanaka et al, 1976)...

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