Ethyl malonate ester

Ethylmalonic Acid.—Like acetoacetic ester (see p. 83), diethylmalonate contains the gioup CO.CHj.CO. By the action of sodium or sodium alroholate, the hydrogen atoms of the methylene group are successively replaceable by sodium. The sodium atoms are in turn replaceable by alkyl or acyl groups. Thus, in the present preparation, ethyl malonic ester is obtained by the action of ethyl iodide on the monosodium compound. If this substance be treated with a second molecule of sodium alcoholate and a second molecule of alkyl iodide, a second radical would be in roduced, and a compound formed of the general formula... 

The ethyl malonic ester (10 gms.) is hydrolysed by boiling for an hour on the water-bath with strong aqueous potash containing 15 gms. of potash. The product is treated with moderately strong hydrochloric acid till neutral, and the acid is then precipitated as the calcium salt by adding a concentrated solution of calcium chloride. The salt is filtered and decomposed by strong hydrochloric acid and the free ethyl malonic acid extracted with ether. The ether extract deposits crystals on evaporation, and these may be recrystallised from a small quantity of boiling water. Colourless prisms, m.p, 111 5°, Yield, about 5 gms. 

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... 

Sodium malonic ester Ethyl malonic ester... 

Weems, on electrolyzing the sodium salt of methylmalonic ester in alcoholic solution, obtained dimethyl-etharie-tetracarboxylic ester ethyl-malonic ester yielded diethyl-etkane-tetracarboxylic ester and aceto-acetic ester was changed to diacetyl-succinic ester. 

When an ethanolic solution of the sodium derivative of ethyl malonate is. shaken with a solution of iodine, the latter withdraws the sodium, and the ethyl malonate residues link together in pairs to give the tetra-ethyl ester of... 

Ethane tetracarboxylic ethyl ester can be regarded as composed of two malonic ester residues, each acting as a mono-alkyl substituent to the other. The two remaining hydrogen atoms therefore still retain acidic properties, and consequently the ester gives with sodium ethoxide a di-sodium derivative. 

Extremely dry (or super-dry ) ethyl alcohol. The yields in several organic preparations e.g., malonic ester syntheses, reduction with sodium and ethyl alcohol, veronal synthesis) are considerably improved by the use of alcohol of 99-8 per cent, purity or higher. This very high grade ethyl alcohol may be prepared in several ways from commercial absolute alcohol or from the product of dehydration of rectified spirit with quicklime (see under 4). 

Where R and R are identical, the dialkylmalonic ester may be prepared in one operation by treating 1 mol of ethyl malonate with 2 mots each of sodium ethoxide and the alkyl halide (usually bromide or iodide). 

Remove the ether using the apparatus shown in Fig. II, 13, 4 except that a 200 ml. Claisen flask replaces the distilling flask depicted in the diagram. Distil the residual ester vmder diminished pressure (Fig. II, 20, 1) and collect the ethyl malonate at 92-94°/16 mm. The yield is 105 g. 

The addition of active methylene compounds (ethyl malonate, ethyl aoeto-acetate, ethyl plienylacetate, nltromethane, acrylonitrile, etc.) to the aP-double bond of a conjugated unsaturated ketone, ester or nitrile In the presence of a basic catalyst (sodium ethoxide, piperidine, diethylamiiie, etc.) is known as the Michael reaction or Michael addition. The reaction may be illustrated by the addition of ethyl malonate to ethyl fumarate in the presence of sodium ethoxide hydrolysis and decarboxylation of the addendum (ethyl propane-1 1 2 3-tetracarboxylate) yields trlcarballylic acid ... 

Compounds which dissolve in concentrated sulphuric acid may be further subdivided into those which are soluble in syrupy phosphoric acid (A) and those which are insoluble in this solvent (B) in general, dissolution takes place without the production of appreciable heat or colour. Those in class A include alcohols, esters, aldehydes, methyl ketones and cyclic ketones provided that they contain less than nine carbon atoms. The solubility limit is somewhat lower than this for ethers thus re-propyl ether dissolves in 85 per cent, phosphoric acid but re-butyl ether and anisole do not. Ethyl benzoate and ethyl malonate are insoluble. 

Alcohols, esters (but not ethyl benzoate, ethyl malonate or ethyl oxalate), aldehydes, methyl ketones and cyclic ketones containing less than nine carbon atoms as well as ethers containing less than seven carbon atoms are soluble in 85 p>er cent, phosphoric acid. 

Hydrogenolysis of the diallyl alkylmalonate 757 with formic acid in boiling dioxane affords the monocarboxylic acid 758. Allyl ethyl malonates are converted into ethyl carboxylates[471]. The malonic allyl ester TV-allylimide 759 undergoes smooth deallylation in refluxing dioxane to give the simple imide 760(472]. The allyl cyanoacetate 761 undergoes smooth decarboxylation to give... 

The properties of diethyl malonate that make the malonic ester synthesis a useful procedure are the same as those responsible for the synthetic value of ethyl acetoacetate The hydrogens at C 2 of diethyl malonate are relatively acidic and one is readily removed on treatment with sodium ethoxide... 

The most convenient synthesis of 6-hydroxy-2-pyridones is by the condensation of a P-ketoester, eg, ethyl acetoacetate, with an active methylene compound, eg, malonic ester, cyanoacetic ester, and an amine. The amine can be omitted if an acetamide is used and in some cases this modification results in a higher yield. 

These compounds yield, on hydrolysis, the free acids, which, like all acids containing two carbo.xyl groups attached to the same carbon atom, lose COj on heating. Thus, ethyl malonic acid yields butyric acid. In this way the synthesis of monobasic acids may be readily effected. Malonic ester, moreover, may be used in the preparation of cyclic compounds as well as of tetrabasic and also dibasic acids of the malonic acid series ( Perkin). To give one illustration malonic ester, and ethylene bromide in presence of sodium alcoholate, yield triniethyleiic dicarbo.xylic ester and tetramethylene tetracarbo.xylic ester. The first reaction takes place in two steps,... 

The rate of the alkylation reaction depends on the enolate concentration, since it proceeds by a SN2-mechanism. If the concentration of the enolate is low, various competitive side-reactions may take place. As expected, among those are E2-eliminations by reaction of the alkyl halide 2 with base. A second alkylation may take place with mono-alkylated product already formed, to yield a -alkylated malonic ester however such a reaction is generally slower than the alkylation of unsubstituted starting material by a factor of about 10. The monoalkylation is in most cases easy to control. Dialkylated malonic esters with different alkyl substituents—e.g. ethyl and isopropyl—can be prepared by a step by step reaction sequence ... 

Ethyl Malonate.—Ethyl malonate is not a member of the parafiinoid acid esters, but is sufficiently nearly related to this series to be included here as a matter of convenience. It is of considerable value in modifying flower odours, having a more or less characteristic apple odour, but of a much sweeter type than the valerianic ester perfume. It is an oil of specific gravity 1 068, and boils at 198°. 

Anschutz 1 treated aceto-salicylic chloride with sodium-malonic ester, with the formation of ethyl acetate and y3-hydroxy-coumarin-alpha-car-hoxylic ethyl ester—... 

Ethyl 3-oxobutanoate, commonly called ethyl acetoacetate or ace tome tic ester, is much like malonic ester in that its ct hydrogens are flanked by two carbonyl groups. It is therefore readily converted into its enolate ion, which can be alkylated by reaction with an alkyl halide. A second alkylation can also be carried out if desired, since acetoacetic ester has two acidic a hydrogens. 

A more general method for preparation ofa-amino acids is the amidotnalmatesynthesis, a straightforward extension of the malonic ester synthesis (Section 22.7). The reaction begins with conversion of diethyl acetamidomalonate into an eno-late ion by treatment with base, followed by S 2 alkylation with a primary alkyl halide. Hydrolysis of both the amide protecting group and the esters occurs when the alkylated product is warmed with aqueous acid, and decarboxylation then takes place to vield an a-amino acid. For example aspartic acid can be prepared from, ethyl bromoacetate, BrCh CCHEt ... 

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