Methyl Pentanoic Acid

CH3CH2CH(CH3)CH(C02K)2 + 2C2H5OH CH3CH2CH(CH3)CH(C02K)2 + H2SO4 -  

Submitted by E. B. Vliet, C. S. Marvel, and C. M. Hsueh. Checked by Henry Gilman and R. E. Brown. 

A solution of 200 g. (3.57 moles) of potassium hydroxide (Note 1) in 200 cc. of water is placed in a 2-1. round-bottom flask fitted with a reflux condenser, a mechanical stirrer and a separatory funnel. The stirrer is started and to the hot solution 200 g. (0.92 mole) of ethyl sec.-butylmalonate (Note 2) is added slowly. The solution refluxes gently due to the heat of saponification. After all of the sec.-butylmalonic ester has been added, the solution is refluxed gently for two hours. The solution is diluted with 200 cc. of water and 200 cc. of liquid is then distilled from the solution. This is done in order to remove all of the alcohol formed during the saponification (Note 3). 

The solution is allowed to cool and a cold solution of 320 g. (3.3 moles) of concentrated sulphuric acid (Note 4) in 450 cc. of water is added through the separatory funnel. This should be done slowly and with stirring in order to prevent foaming. The solution becomes hot and may reflux spontaneously. After all of the sulfuric acid has been added the solution is refluxed for about three hours. A layer of organic acid appears and the reflux condenser is replaced by an automatic separator (Org. 

68) (Note 5). The solution is distilled with the separator, and the aqueous portion is returned to the distilling flask. This operation is continued until practically all of the organic acid has been driven over. This requires from ten to fifteen hours. At the end, about 100 cc. of water is collected in the separator and extracted with ether in order to remove the dissolved acid (Note 6). The ether is distilled and the crude acid is mixed with an equal volume of dry benzene (Note 7) and distilled through a fractionating column (Org. Syn. i, 40). Benzene and water distil first and then the 3-methyl pentanoic acid distils at 193-i96°/743 mm. The yield is 66-69 g- (62—65 per cent of the theoretical amount) (Note 8). 

Sodium hydroxide is unsatisfactory for this saponification because an organic sodium salt separates, yielding a semi-solid mass. 

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Benzyl cyanide is first reacted with 2-butylbromide in the presence of sodium amide to give 2-phenyl-3-methylvaleronitrile which is hydrolyzed by sulfuric acid to give 3-methyl-2-phenyl-pentanoic acid. 24 g of 2-phenyl-3-methyl-pentanoic acid are heated for one hour at 175° to 185°C with 30 g of 2-diethylaminoethanol and 0.5 g of sodium methylate. The excess diethyl-aminoethanol is removed in vacuo, the residue is dissolved in 300 cc of 2 N-acetic acid, the acid solution is shaken with ether and made alkaline with concentrated potassium carbonate solution and ice. The ether solution Is washed with water, dried with sodium sulfate and evaporated. The residue is distilled under high vacuum, yielding 20 to 21 g of the basic ester (60% of the theoretical) is obtained, the ester boiling at 98° to 100°C at a pressure of 0.03 mm. The hydrochloride of the ester melts at 112° to 113°C and the methobromide at 100° to 101°C. 

An independent proof of this finding was recently obtained by Ciardelli, Benedetti, Pieroni and Pino (23, 24) who prepared an atactic poly-(S)-4-xnethyl-1-hexene having [M] >5 = +190 from a poly-(S)-4-methyl-l-hexyne having an optical purity of about 89.5% as demonstrated by the optical purity of (S)-3-methyl-pentanoic acid obtained by ozonization of the unsaturated polymer. The rotatory power of the polymer thus prepared is very near to the rotatory power of the non crystallizable poly-(S)-4-methyl-l-hexene obtained from a monomer having a 93% optical purity (see Table 8). 

The ethyl sec,-butylmalonate was prepared from sec-butyl bromide and malonic ester according to the general method described in Org. Syn. 4, n. The yield of ester boiling at i24-i32°/28 mm. was 80-81 per cent of the theoretical amount. The yields of 3-methyl pentanoic acid given in this procedure were obtained with this grade of ester. 

Methyl oxalate, 10, 70 3-Methyl pentanoic acid, 11, 76 Myristyl alcohol, 10, 64... 

This amino acid, as the name indicates, is isomeric with leucine. It is the alpha-anmno derivative of another of the isomeric six carbon acids, viz., 3-methyl pentanoic acid. 

Methyl pentanoic acid has always been prepared by heating ec.-butyl malonic acid. ... 

Mevalonic acid [(MVA, (/f)-3,5-dihydroxy-3-methyl-pentanoic acid, hiochic acid]. 

Figure 2 Chemical structures of representative fluorinated amino acids 3,3,3-trifluoroalanine (Tfa), 2-amino-4,4,4-trifluorobutyric acid (Atb), 4,4-difluoroethylglycine (Dfeg), 4,4,4-trifluorovaline (Tfv), 5,5,5-trifluoroleucine (Tfl), 5,5,5,5, 5, 5 -hexafluoroleucine (Hfl), 2-amino-3-trifluoromethylpentanoic acid (3Tfl), 2-amino-5,5,5-trifluoro-3-methyl pentanoic acid (5Tfi), 5,5,5, 5 -tetrafluoroleucine (Qfl), pentafluorophenylalanine (Pff), 2,3,4,5-tetrafluorophenylalanine (o-Qff), and 2,3,5,5-tetrafluorophenylalanine (p-Qff).

Complete cleavage of the macromolecules to low molecular weight products can be achieved easily when double bonds are present in the main chain. Thus in the case of poly-l-alkynes low molecular weight carboxylic acids can be obtained by ozonolysis accordingly by oxidative cleavage of poly-( S )-4-methyl-l-hexyne, optically active 3-methyl-pentanoic acid was obtained with the same optical purity as the starting 4-methyl-l-hexyne [27] (Scheme 1). 

Hmpa 3-hydroxy-3-methyl-pentanoic acid - Lac lactic acid - Pla 3-phenyllactic acid - Pval phenylvaline... 

C9H15 N02 2-cyano-3-methyl-pentanoic acid ethyl ester ... 

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