Glutaric acid 2- 4-

Glutaric Acid HOOC—CH2—CHj—CH2—COOH. Pentan-di-oic Acid 

Malonic acid Mono-methyl malonic acid Iso-succinic acid 1 COOH Sucdnic acid 

Succinic acid Mono-methyl succinic acid Pyro-tartaric acid 1 

This new acid, isomeric with mono-methyl succinic acid, pyro-tartaric acid, is known as glutaric acid, or systematically, as 1-5-pen-tan-di-oic acid. 

Synthesis from Propane.—The constitution of glutaric acid as i 5-pentan-di-oic acid is proven by its synthesis from 1-3-di-cyano propane which in turn is prepared from 1-3-di-brom propane, as follows  

Submitted by J. English, Jr., and J. E. Dayan. Checked by Arthur C. Cope and Mark R. Kinter. 

In a 1-1. round-bottomed flask equipped with a reflux condenser are placed 400 ml. of 0.2 N nitric acid (5 ml. of concentrated nitric acid, sp. gr. 1.42, and 395 ml. of water) and 168.3 g. (2 moles) of dihydropyran (Note 1). The mixture is heated on a steam bath or a boiling water bath the yellowish upper layer dissolves suddenly after 25 to 45 minutes of heating. The flask is swirled to aid the dissolution at this time, and the period of heating is extended for an additional 5 to 10 minutes. 

While the hydrolysis of the dihydropyran is taking place, 800 g. (575 ml., 9.25 moles) of concentrated nitric acid (sp. gr. 1.42) is placed in a 2-1. three-necked flask and cooled in an ice-salt bath in a well-ventilated hood. The flask should be equipped with an efficient stirrer, separatory funnel, reflux condenser, and a thermometer. When the temperature of the solution reaches 0°, 5.75 g. of sodium nitrite is added and stirring is continued until most of it has dissolved the solution becomes yellow. 

Dihydropyran is available from the Electrochemicals Department, E. I. du Pont de Nemours and Company, or can be prepared by the dehydration of tetrahydrofurfuryl alcohol.1 

More efficient cooling may shorten the time required for the addition. 

Most of the ether can be recovered by concentrating the solution in a flask attached to a condenser set for distillation. 

The glutaric acid may be directly extracted from the ammonium chloride with benzene, but this is less satisfactory on a small scale than is the procedure given. 

When the benzene solution is chilled to o° or lower, almost all of the glutaric acid separates in the first crop of crystals. 

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 

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Isocroionic acid, -crotonic acid, cis-croionic acid. Colourless needles m.p. 14 C, b.p. 169 C. Prepared by distilling -hydroxy-glutaric acid under reduced pressure. Converted to a-crotonic acid by heating at 180 C, or by the action of bromine and sunlight on an aqueous solution. 

Anhydrides of dibasic acids (succinic or glutaric acid type) may be prepared ... 

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 ... 

In a 2-litre round-bottomed flask, equipped with a double surface condenser, place 60 g. of triniethylene dicyanide (Section 111,114) and 900 g. of 50 per cent, sulphuric acid (by weight). Reflux the mixture for 10 hours and allow to cool. Saturate the solution with ammonium sul phate and extract wit-h four 150 ml. portions of ether dry the ethereal extracts with anhydrous sodium or magnesium sulphate. Distil off the ether on a water bath the residual glutaric acid (69 g.) crystallises on cooling and has m.p. 97-97-5°. Upon recrystalhsation from chloroform, or benzene, or benzene mixed with 10 per cent, by weight of ether, the m.p. is 97 -5-98°. 

An alternative method of separation consists in treating the dry residue several times with a warm mixture of benzene and ether. The residual solid (about 20 g.) is moderately pure succinic acid, m.p. 183-184°. Upon evaporating the benzene - ether extract, and recrystallising the residue from chloroform or from benzene, about 70 g. of glutaric acid, m.p. 95-96°, are obtained. 

In the above reaction one molecular proportion of sodium ethoxide is employed this is Michael s original method for conducting the reaction, which is reversible and particularly so under these conditions, and in certain circumstances may lead to apparently abnormal results. With smaller amounts of sodium alkoxide (1/5 mol or so the so-called catal3rtic method) or in the presence of secondary amines, the equilibrium is usually more on the side of the adduct, and good yields of adducts are frequently obtained. An example of the Michael addition of the latter type is to be found in the formation of ethyl propane-1 1 3 3 tetracarboxylate (II) from formaldehyde and ethyl malonate in the presence of diethylamine. Ethyl methylene-malonate (I) is formed intermediately by the simple Knoevenagel reaction and this Is followed by the Michael addition. Acid hydrolysis of (II) gives glutaric acid (III). 

The last-named reaction provides an excellent method for the preparation of a-substituted glutaric acids the intermediate alkyl (aryl) -2-cyanoethyl-malonate is both hydrolysed and decarboxylated re ily by boiling with an excess of 48 per cent, hydrobromic acid solution. 

Carbonylation of butyrolactone using nickel or cobalt catalysts gives high yields of glutaric acid [110-94-1] (163). 

In addition to its ptincipal use in biocide formulations (94), glutaialdehyde has been used in the film development and leather tanning industries (95). It may be converted to 1,5-pentanediol [111 -29-5J or glutaric acid [110-94-1]. 

Acryhc esters dimerize to give the 2-methylene glutaric acid esters catalyzed by tertiary organic phosphines (37) or organic phosphorous triamides, phosphonous diamides, or phosphinous amides (38). Yields of 75—80% dimer, together with 15—20% trimer, are obtained. Reaction conditions can be varied to obtain high yields of trimer, tetramer, and other polymers. 

Finally, when polyamides containing four or five carbon diacids, ie, succinic acid [110-15-6] and glutaric acid [110-94-1], respectively, are heated, they form cychc imides that cap the amine ends and prevent high molecular weights from being achieved (84). For nylon-x,4, n = 1 and for nylon-x,5, n = 2. 

Pigment retention and drainage additives made with polyamines include polyamines made from ethyleneamines, ethan olamines, and epichl orohydrin (262) ethyleneamines combined with phosphoms-modifted polyamines made by reaction of ethyleneamines with POCl [10025-87-3] (263) and a DETA—glutaric acid polyamide crosslinked with PEG-bis(3-chloro-2-hydroxypropyl) ether (264). Polyamines made from ethyleneamines and EDC are useful flocculating agents (265). 

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). 

Miscellaneous Derivatives. Fimehc acid is used as an intermediate in some pharmaceuticals and in aroma chemicals ethylene brassylate is a synthetic musk (114). Salts of the diacids have shown utUity as surfactants and as corrosion inhibitors. The alkaline, ammonium, or organoamine salts of glutaric acid (115) or C-5—C-16 diacids (116) are useflil as noncorrosive components for antifreeze formulations, as are methylene azelaic acid and its alkah metal salt (117). Salts derived from C-21 diacids are used primarily as surfactants and find apphcation in detergents, fabric softeners, metal working fluids, and lubricants (118). The salts of the unsaturated C-20 diacid also exhibit anticorrosion properties, and the sodium salts of the branched C-20 diacids have the abUity to complex heavy metals from dilute aqueous solutions (88). 

The water solubiUty of glutaric acid fosters its toxicity. Glutaric acid is a known nephrotoxin. Renal failure has been documented ia rabbits adruinistered sodium glutarate subcutaneously (124). Dibasic ester (Du Pont), which contains primarily dimethyl glutarate, has low acute toxicity by inhalation and by ingestion, and is moderately toxic via dermal absorption. The acid is both a dermal and ocular irritant of humans. The ester is a severe skin irritant and may cause a rash ia humans (120). 

A number of examples of enantioselective hydrolysis of diesters (I and 2) of malonic and glutaric acids are given in Table I. 

Chiral 3-substituted glutaric acid monoester (23) can be obtained via Pseuehmonasfiuoreseens hpase-catalyzed nucleophihc ting opening of anhydride (22) by butanol (38). 

Glutaric acid, 2-phthalimido-polymerization, 1, 273 Glutaric anhydride polymers, 1, 313... 

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. 

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