Methyl Ethyl Acetic Acid

Submitted by Henry Gilman and H. H. Parker Checked by H. T. Clarke and M. R. Bremen. 

In a 2-1. three-necked flask, fitted with a mechanical stirrer, condenser, thermometer well, and 500-cc. separatory funnel, is placed 48 g. (2 moles) of magnesium shavings. The shavings are then covered with 200 cc. of anhydrous ether. A solution of 274 g. (2 moles) of secondary butyl bromide (Note 1) in 300 cc. of anhydrous ether is dropped slowly on to the magnesium. Only a small amount should be added before the reaction starts. The well-stirred mixture is allowed to remain at room temperature during the addition which requires from two to three hours. When the secondary butyl bromide has all been added, the reaction is practically complete and further stirring or refluxing is unnecessary. An additional 500 cc. of anhydrous ether is added. 

The reaction flask is then surrounded by an ice and salt mixture, and carbon dioxide is introduced above the surface with stirring. The rate of flow is regulated so that the temperature of the reaction mixture does not rise above +2°. The gas, obtained directly from a cylinder, is dried by passing through two wash bottles containing concentrated sulfuric acid and is admitted to the flask through an entry tube 10 mm. in diameter, at a height 

The reaction mixture is then hydrolyzed in the flask with 25 per cent sulfuric acid (Note 3). Cooling the solution with ice and water permits of rapid hydrolysis without danger of loss of the material through too vigorous refluxing. The mixture is transferred to a 2-1. separatory funnel and the ether layer separated. The water layer is extracted with three 100-cc. portions of ether. The combined ether extracts are washed with 25 per cent sodium hydroxide solution until all of the organic acid is converted to the salt and thus removed (Notes 4 and 5). About 300 cc. of the sodium hydroxide solution is required. 

The alkaline extract is distilled to remove ether and other volatile impurities. It is then acidified with concentrated hydrochloric acid and the acid layer separated. The water layer is distilled from a 2-1. flask until no more oily acid comes over (Note 6). The distillate is saturated with salt and the acid layer separated. This water layer, together with the low-boiling fraction from the acid distillation, is distilled, and the distillate salted out as before. 

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The isomeric valerianic acids have the formula C Hj O.. Normal valerianic acid does not appear to be found in any essential oils. Iso-valerianic acid, (CHg). jCH. CH. COOH, is found in valerian and other oils it is a liquid boiling at 174°, of specific gravity -947. Another isomer, also found in champaca and coffee oils, is methyl-ethyl-acetic acid, (C.,Hg)(CH3). CH. COOH. This is an optically active liquid, boiling at 175°, of specific gravity -941 at 21°. 

Methylene Iodide, 1, 57 7, 90 0-Methyl Esculetin, 4, 45 df-METHYL Ethyl Acetic Acid, 5,75 Methyl formate, 3, 67 a-M ETHYL d-GLUCOSIDE, 6, 64... 

Methyl ethyl Acetic acid ketone ethyl ester... 

The methyl ethyl acetic acid may also be obtained by extraction of the acidified solution with ether. This method is not recommended, as small amounts of alcohol which are invariably present in this solvent, contaminate the product by the formation of the ethyl ester. 

Methylene iodide, I, 57-59 /3-Methyl esculetin, IV, 45-46 (//-Methyl ethyl acetic acid, V, 75-77 Methyl formate, III, 67 Methyl hexyl carbinol, I, 61-66 Methyl iodide, I, 57, 59 5-Methyl isatin, V, 74 Methyl o-nitrobenzoate, III, 72 Methyl m-nitrobenzoate, III, 71-72, 73-Methyl oxalate, V, 60 Methyl Red, II, 47-51... 

Methyl ethyl acetic acid may be prepared from methyl ethyl malonic ester by hydrolysis and subsequent heating of the methyl ethyl malonic acid.1 The yield by this method, in the preparation of large quantities, is about 61 per cent of the theoretical amount based on the malonic ester used. The acid was first prepared by Saur2 from methyl ethyl acetoacetic ester. It has also been made by oxidation of the corresponding aldehyde with chromic acid.3... 

Champaca oil contains henzyl alcohol, linalol, geraniol, esters of methyl-ethyl acetic acid, methyl anthranilate, isoeugenol, henzoic acid, methyl eugenol, and a crystalline body melting at 165 to 166 , of the formula... 

C21H21N3O9 4199-35-3) see Minocycline (/ )-[2-(dimethylamino)-2-oxo-l-[(phenylthio)methyl] ethyl]carbamic acid phenylmethyl ester (C,9H22N20iS 197302-34-4) see Nelfinavir mesylate lV-[3-[3-(dimethylamino)-l-oxo-2-propenylJphenyl]acet-amide... 

Note TLC was performed on silica gel, and the solvents were (1) -bntanol/glacial acetic acid/water (2 1 1, v/v), (IV) isoamyl alcohol/ethy methyl ketone/glacial acetic acid/water (40 40 7 13, v/v), (VII) n-bntanol/2-propanol/water/glacial acetic acid (30 50 10 2, v/v), (VIII) ethyl methyl ketone/acetic acid/methanol (3 1 1, v/v), and (IX) n-bntanol/benzyl alcohol/glacial acetic acid (8 4 3, v/v). 

Acetic acid, methyl ester Acetic acid, ethyl ester Pentanoic acid, methylethyl ester Acetic acid, methylethyl ester Acetic acid, 3-propenyl ester Acetic acid, benzyl ester Oxalic acid, dimethyl ester Oxalic acid, diethyl ester Oxalic acid, fe(l-methylethyl) ester... 

Acetic Acid, Cupric Salt Acetic Acid, Dimethylamide Acetic Acid, Ethyl Ester Acetic Acid, Isobutyl Ester Acetic Acid, Isopropyl Ester Acetic Acid, Methyl Ester Acetic Acid, Nickel (II) Salt Acetic Acid, Propyl Ester Acetic Acid, Sec-Butyl Ester Acetic Acid, Zinc Salt Acetic Aldehyde Acetic Anhydride Acetic Ester Acetic Ether... 

Note Highly polar solvent sweet, ethereal odor soluble in water flammable, burns with a luminous flame highly toxic by ingestion, inhalation and skin absorption miscible with water, methanol, methyl acetate, ethyl acetate, acetone, ethers, acetamide solutions, chloroform, carbon tetrachloride, ethylene chloride, and many unsaturated hydrocarbons immiscible with many saturated hydrocarbons (petroleum fractions) dissolves some inorganic salts such as silver nitrate, lithium nitrate, magnesium bromide incompatible with strong oxidants hydrolyzes in the presence of aqueous bases and strong aqueous acids. Synonyms methyl cyanide, acetic acid nitrile, cyanomethane, ethylnitrile. 

SYNS ACETATE de METHYLE (FRENCH) ACETIC ACID METHYL ESTER DEVOTON ETHYL ESTER ofMONOACETIC ACID METHYLACETAAT (DUTCH)... 

Poiseuille" found for mixtures of ethyl alcohol and water a maximum of viscosity for the proportions C2H6O+3H2O this was confirmed by Graham, who also foimd maxima for aqueous solutions of methyl alcohol, acetic acid, nitric acid, etc., the maximum being proportional to the molecular weight. Wijkander, and Traube, found that the position of the maximum depends oh the temperature for mixtures of water with acetic acid and ethyl alcohol, respectively. 

Ethyl alcohol Methyl alcohol Acetic acid... 

Ethyl ester of methyl aceto acetic acid... 

A soln. of a-ethoxydiphenylacetic acid in methanol electrolyzed (s. Synth. Meth. Sy 299) henzophenone methyl ethyl acetal. Y 74%.—Similarly a-Ethoxyphenylacetic acid henzaldehyde methyl ethyl acetal. Y 71.4%, F. acetals s. B. Wladislaw and A. M. J. Ayres, J. Org. Chem. 27, 281 (1962) electrolysis of -arylthiocarboxylic acids cf. Chem. Ind. 1962, 1868. 

Mix 6 2 ml. (6 4 g.) of pure ethyl acetoacetate and 5 ml. of pure phenylhydrazine in an evaporating-basin of about 75 ml. capacity, add 0 5 ml. of acetic acid and then heat the mixture on a briskly boiling water-bath (preferably in a fume-cupboard) for I hour, occasionally stirring the mixture with a short glass rod. Then allow the heavy yellow syrup to cool somewhat, add 30-40 ml. of ether, and stir the mixture vigorously the syrup may now dissolve and the solution shortly afterwards deposit the crystalline pyrazolone, or at lower temperatures the syrup may solidify directly. Note. If the laboratory has been inoculated by previous preparations, the syrup may solidify whilst still on the water-bath in this case the solid product when cold must be chipped out of the basin, and ground in a mortar with the ether.) Now filter the product at the pump, and wash the solid material thoroughly with ether. Recrystallise the product from a small quantity of a mixture of equal volumes of water and ethanol. The methyl-phenyl-pyrazolone is obtained... 

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