Methylglutaric Acid

FIGURE 3.54 3-Methylglutaric acid in D20. (A) at 300 MHz. (B) at 600 MHz. The COOH peak exchanges with the D20 therefore is not shown. 

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P-Methylglutaric acid [626-51-7] M 146.1, m 87 , pK 4.35, pKj 5.44. Crystd from distd water, then dried under vacuum over cone H2SO4. 

B. -Ethyl-fi-methylglutaric acid. A mixture of 280 g. (1.36 moles) of K,a -dicyano- -ethyl- -methylglutarimide (Note 5) and 1.35 1. of 65% (by weight) sulfuric acid is heated under reflux in a 5-1. round-bottomed flask for 8-10 hours (Note 6). The mixture is allowed to cool, and the precipitate is removed by filtration on a sintered glass (or other suitable type) filter. The crude -ethyl-/3-methylglutaric acid is recrystalhzed from water (Note 7). The yield of product is 174-191 g. (73-80%), m.p. 78-80°. 

In taking the melting point of this compound there was still some solid remaining at 200°. The crude imide is satisfactory for conversion to /3-ethyl-/3-methylglutaric acid and need not be dried before hydrolysis. 

AdipoH ire, n. adipocere. -malsaure, /. adi-pomalic acid (o -hydroxy-a methylglutaric acid). 

Three other portions of the molecule which do not fit the polyketide combination pattern (Scheme 7B a,f,n) can be also explained by assuming they are derived from a dicarboxylic acid such as 3-hydroxy-3-methylglutaric acid (Scheme 8b). If that is the case, brevetoxins are a new type of mbced polyketides which are formed by condensation on both ends of dicarboxylic acids (Scheme 8c). In order to prove further the hypothesis, feeding experiments with such putative precursors as succinate, acetoacetate, and propionate are in progress. 

The above method is adapted from the procedure of Day and Thorpe.1 /3-Methylglutaric acid has been prepared by hydrolysis of jS-methylglutaronitrile 2 by condensation of crotonic ester with ethyl sodiocyanoacetate, and with sodiomalonic ester 3 4 and by condensation of acetaldehyde with malonic ester. ... 

B) /3-Methylglutaric Acid.—In a 5-1. flask are placed 400 g. of the amide and 11. of concentrated hydrochloric acid the mixture is warmed on a steam bath until solution is complete, after which it is diluted with 1 1. of water and refluxed for eight hours. The amber-colored solution is saturated with sodium chloride and extracted with five 600-cc. portions of ether. The combined ether extracts are dried for one hour over phosphorus pentoxide, and the solvent is removed by distillation. The residue, crude /3-methylglutaric acid, weighs 238-240 g. (80 per cent of the theoretical amount) and melts at 79-82° with previous softening. This product is recrystallized from about 250 cc. of 10 per cent hydrochloric acid. The recovery is about 90 per cent (Note 4), and the purified product melts at 85-86°. 

There is a very close resemblance between the vinyl polymers and those derived from symmetric monomers like 3-methyloxetane, 38, (80) or from the condensation of 3-methylglutaric acid with ethylene glycol or ethylenediamine. 

Dimerization of methyl crotonate has been carried out with alkaline earth metal oxides as basic catalysts 15). The reaction proceeds by Michael addition, which is initiated by abstraction of an allylic hydrogen of methyl crotonate by the basic site to form the allylic carbanion, which attacks a second methyl crotonate molecule at the jS-position to form a methyl diester of 3-methyl-2-vinylglutaric acid. The diester undergoes a double bond migration to form the final E- and Z- isomers of 3-ethylidene-3-methylglutaric acid dimethyl ester (MEG) (Scheme 22). 

Methylheptanoic acid has been prepared by mixed electrolysis of / -methylglutaric acid monomethyl ester and butyric acid, followed by saponification of the methyl ester,10 and by the mal-onic ester synthesis from 2-bromohexane.11 The present method7 has the advantage of avoiding the use of secondary bromides, which are often difficult to secure entirely pure.12... 

The reduction of acrylic acid was attempted at elevated temperatures. Surprisingly, the reaction was found to yield not only propionic acid, but also the dimer, a-methylglutaric acid. When the reaction was conducted in the absence of hydrogen, the product obtained was 3-methylglutaconic acid, which apparently is the precursor of the saturated dimer formed in a hydrogen atmosphere. Similarly, methacrylic acid yielded a-methylene-y,y-dimethylglutaric acid when heated with cyanocobaltate (II) in the absence of hydrogen. Its structure was established via ozonolysis. Similar dimerizations have been reported for acrylic acid (I, 14), methacrylate ester (7, 11), crotonic acid (13), and its diethylamide (15). 

Hydroxy-3-methylglutaric acid [503-49-1] M 162.1, m 99-102 . Recrystd from ethyl ether/hexane and dried under vac at 60° for 1 h. 

Dimethylamino-6-methoxy-3-methyl-4//-pyran (96a) underwent an acidic hydrolysis with diluted HC1 or TsOH to 2-methylglutaric acid derivatives Me02CCH2CH2CH(Me)C0X with X = MeO or Me2N.144... 

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