Glutaric acid, oxidation

The oxidation of cyctopentanone (Section 111,73) with dilute nitric acid gives glutaric acid accompanied by some succinic acid the latter is removed as the sparingly-soluble barium salt ... 

Although many variations of the cyclohexane oxidation step have been developed or evaluated, technology for conversion of the intermediate ketone—alcohol mixture to adipic acid is fundamentally the same as originally developed by Du Pont in the early 1940s (98,99). This step is accomplished by oxidation with 40—60% nitric acid in the presence of copper and vanadium catalysts. The reaction proceeds at high rate, and is quite exothermic. Yield of adipic acid is 92—96%, the major by-products being the shorter chain dicarboxytic acids, glutaric and succinic acids,and CO2. Nitric acid is reduced to a combination of NO2, NO, N2O, and N2. Since essentially all commercial adipic acid production arises from nitric acid oxidation, the trace impurities patterns ate similar in the products of most manufacturers. 

Several procedures for making glutaric acid have been described in Organic Syntheses starting with trimethylene cyanide (28), methylene bis (malonic acid) (29), y-butyrolactone (30), and dihydropyran (31). Oxidation of cyclopentane with air at 140° and 2.7 MPa (400 psi) gives cyclopentanone and cyclopentanol, which when oxidized further with nitric acid at 65—75° gives mixtures of glutaric acid and succinic acid (32). 

Glutaric acid is easily and cheaply prepared by oxidation of cyclopentanone cf. Adipic Acid, Coll. Vol. i, 18. The oxidation needs careful control—if it gets out of hand succinic acid results. 

If a-phellandrene be oxidised by potassium permanganate, the principal body resulting is a-oxy-/3-isopropyl glutaric acid. If /3-phellandrene be oxidised, closely related acids result, but if a 1 per cent, solution of permanganate be used and the oxidation effected very carefully in the cold, with the terpene always in excess, a glycol, CjoHjg(OH)2, results, which when dehydrated with dilute sulphuric acid yields tetrahydro-cuminic aldehyde. 

Glutarimides may be regarded as oxidized piperidines, and many drugs containing this moiety are sedatives and anticonvulsants. A spiro derivative, alonimid (105) is such a sedative-hypnotic agent. It can be prepared by K t-butoxide catalyzed biscyano-ethylation of phenylacetonitrile, leading to 101. Alkaline hydrolysis produces tricarboxylic acid 102 which is smoothly Converted to the glutaric acid anhydride (103) with acetic anhydride. Friedel-Crafts... 

Glutarimide has been prepared from glutaric acid and sulfamide 3 or formamide,4 by distillation of ammonium glutarate,6 by hydrolysis of pentanedinitrile with acetic acid,6 and by oxidation of piperidine with hydrogen peroxide.7... 

Organic aerosols formed by gas-phase photochemical reactions of hydrocarbons, ozone, and nitrogen oxides have been identified recently in both urban and rural atmospheres. Aliphatic organic nitrates, such dicarboxylic acids as adipic and glutaric acids, carboxylic acids derived from aromatic hydrocarbons (benzoic and phenylacetic acids) and from terpenes emitted by vegetation, such as pinonic acid from a pinene, have been identified. The most important contribution in this held has been that of Schuetzle et al., who used computer-controlled... 

GABA acts as an inhibitory transmitter in many different CNS pathways. It is subsequently destroyed by a transamination reaction (see Section 15.6) in which the amino group is transferred to 2-oxoglutaric acid, giving glutaric acid and succinic semialdehyde. This also requires PLP as a cofactor. Oxidation of the aldehyde group produces succinic acid, a Krebs cycle intermediate. 

Figure 11.2 shows a cyclohexane oxidation reactor. The further oxidation of the ketone and alcohol to adipic acid is very complex but occurs in good yield, 94%, despite some succinic and glutaric acid by-products being formed because the adipic acid can be preferentially crystallized and centrifuged. 

Structure 187 was proposed for deoxodihydroleontalbinine. Leontalbinine perchlorate could not be reduced, while deoxoleontalbinine perchlorate was reduced by sodium borohydride. This suggested an a,p position of the double bond with respect to the amine nitrogen, which was confirmed by oxidation to glutaric acid, probably via the intermediate product 189 (Scheme 34). Since structure 188 proposed for leontalbinine is correct, structure 187 given to deoxodihydroleontalbinine is incorrect and has to be changed to 190. 

Oxidation of diethyl 2-aUyl-2-hydroxypentanedioate by RnCyaq. Na(IO )/ CHjCN-EtOAc gave triethyl homocitrate and the corresponding lactone [209]. Oxidation of cyclopentene to glutaric acid by RnCyaq. Na(C10)/CCl or CH Cl showed that addition of CHjCN and also NaOH greatly improved yields [210]. Perfluoro alkenes were cleaved by Ru02/IO(OH)j, Na(ClO) or CH COOOH/water-Freon 113 to carboxylic acids CO was also formed or, in the case of perfluoropro-pene, pefluoroacetic acid and COF (Table 3.6) [211]. 

As the hydrolyzed dihydropyran solution cools, it may become cloudy and 5-hydroxyvaleraldehyde may separate as a red liquid. The separation can be avoided by continuing to heat most of the solution while a small part is left in the separatory funnel, but it is not essential, for the yield is not affected by the separation of phases at this point. Oxidation of the pure aldehyde in a similar manner is stated to give a 90% yield of glutaric acid. ... 

Many methods have been mentioned in the literature for the preparation of glutaric acid. Of these, the only methods of preparative interest are the hydrolysis of trimethylene cyanide with acids or alkalies,1 the hydrolysis of methylene dimalonic ester2 or methylene dicyanoacetic ester,3 and the oxidation of cyclopentanone with nitric acid.4 In this country the cheapness of trimethylene glycol makes it the best source for glutaric acid. The method described in the procedure is a modification of that originally described by Reboul.5... 

Dimethyl-D-arabinose has been obtained29 from 3-/J-D-galacto-pyranosyl-D-arabopyranose, obtained by the Wohl-Zempl6n degradation of lactose, by methylation and hydrolysis. Oxidation with nitric acid gave /9-hydroxy-aY-dimethoxy-D-arabo-glutaric acid, the amide of which was the enantiomorph of the product obtained from 2,4-dimethyl-L-arabinose. 

As mentioned in the introduction, trimethyl-L-arabofuranose is frequently found among the products of hydrolysis of methylated polysaccharides. The sugar was first isolated by the methylation of methyl L-arabofuranosides (a/3 mixture) with silver oxide and methyl iodide.46 Oxidation of the free sugar with nitric acid gave a dimethoxyhydroxy-glutaric acid. 

When 2-methyl-iV-tosylpyrrole was exposed to glutaric acid (0.5 equiv) the 3,4-dihydro-2//-pyran-2-one 388 was obtained (Scheme 85) <2004TL9573>. Further oxidation then gave a moderate but unoptimized return of the 27/-pyran-2-one 389. 

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