Ethyl oxalate

In a large evaporating dish is placed 252 g. (2 moles) of crystalline oxalic acid. The acid is heated on a steam bath for six to eight hours, with occasional stirring, until all the water of crystallization (72 g.) has been expelled. The oxalic acid which is almost anhydrous (weighing approximately 180 g.), is placed in a 1.5-I. round-bottom flask, A, containing 500 cc. of absolute alcohol and fitted up as shown in Fig. 1. 

The flask A is heated by means of an oil bath maintained at 120-125° (Note 1) the mixed vapors of alcohol and water, passing through the fractionating column, are condensed in D and the moist alcohol is delivered under the surface of the alcohol contained in flask B. In flask B are placed 250 cc. of absolute alcohol and about 200 g. of freshly ignited potassium carbonate. Flask B is heated in an oil bath maintained at about 95-100°. The moist alcohol delivered to the flask B is dried by the potassium carbonate and subsequently returned as vapor under the surface of the liquid in flask A. The tube C, which is open to the air, acts as a safety valve to the otherwise closed system. 

The reaction is run for about five hours. The excess alcohol is then distilled, the residue of ethyl oxalate is distilled under reduced pressure, and the fraction boiling at 98-101°/11 mm. is 

A similar procedure may be used for the preparation of methyl oxalate. Instead of distilling this ester, it is better to cool the solution in an ice bath and separate the crystals of 

The esterification of oxalic acid by the method of Clarke,1 in which carbon tetrachloride is used to remove the water from the esterification mixture, is very satisfactory. However, the above procedure, which is based on the method of Frankland and Aston2 for the preparation of ethyl tartrate, is very easily carried out and the yields are as good as those described by Clarke. 

Prepared by H. T. Clarke and Anne W. Davis. Checked by Roger Adams and W. B. Burnett. 

In a 5-I. flask are placed 1 kg. of crystallized (hydrated) oxalic acid, 1.66 kg. of 95 per cent ethyl alcohol, and 1.33 kg. of 

The mixture in the flask is slowly distilled. As soon as about 500 cc. of the lighter liquid has collected, it is placed in a fractionating apparatus and distilled, the material which boils up to 790 being collected separately. This fraction, which consists principally of alcohol, with a little carbon tetrachloride and moisture, is dried with potassium carbonate and returned to the reaction mixture. The higher fractions are redistilled. 

The above process is continued until the distillate no longer separates into two phases (about twenty-seven hours). The liquid in the flask is then distilled with the use of a column until the temperature of the vapor reaches 85° the residue is then distilled under reduced pressure, and the fraction which boils at io6-io7°/25 mm. is collected. The yield is 920-960 g. of a colorless liquid (80-84 Per cent of the theoretical amount). 

ethyl alcohol and carbon tetrachloride form a ternary mixture boiling at about 61 °. This vapor mixture, on condensation, separates into two phases the heavier liquid consists of carbon tetrachloride and alcohol with only small amounts of water the lighter liquid consists of approximately 65 per cent alcohol, 25 per cent water and 10 per cent carbon tetrachloride. By taking advantage of this fact, it is possible to conduct the esterification at a temperature so low that the ethyl hydrogen oxalate first formed does not decompose into ethyl formate and other products, as is the case when the customary methods of esterification are employed. 

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Carry out this preparation in precisely the same way as the above preparation of oxamide, using 2 ml. (2-4 g.) of benzoyl chloride instead of the ethyl oxalate, and observing the same precautions. Considerably more heat is generated in this reaction therefore hold the cork very securely in position during the shaking. After vigorous shaking for 15 minutes, no trace of oily benzoyl chloride remains. Filter off the fine flakes of benzamide, wash with cold water, and then recrystallise from hot water yield, 1-5 g. Colourless crystals, m.p. 130°. 

Dissolve 0 2 g. of methyl oxalate in 10 ml. of water, add without delay 1 ml. of ammonia (d, o 88o) and shake a fine white precipitate of the insoluble oxamide is produced. A precipitate of oxamide is similarly produced when 2-3 drops of ammonia are added directly to 0 5 ml. of ethyl oxalate. 

Ethyl oxalate is the only liquid ester which gives this rapid separation of the amide, which is therefore characteristic. Methyl and ethyl formate react rapidly with ammonia, but the soluble formamide does not separate methyl succinate gives crystalline succinamide after about I hour s standing, other esters only after a much longer time. The solid esters, other than methyl oxalate, are either soluble in water and remain so when treated with ammonia, or alternatively are insoluble in water and hence clearly not methyl oxalate. 

NOTE. Many esters reduce Fehling s solution on warming. This reduction occurs rapidly with the alkyl esters of many aliphatic acids, but scarcely at all with similar esters of aromatic acids (f.g., ethyl oxalate reduces, but ethyl benzoate does not). Note also that this is a property of the ester itself thus both methyl and ethyl oxalate reduce Fehling s solution very rapidly, whereas neither oxalic acid, nor sodium oxalate, nor a mixture of the alcohol and oxalic acid (or sodium oxalate), reduces the solution. 

Diethyl oxalate. Reflux a mixture of 45 g. of anhydrous oxalic acid (1), 81 g. (102-5 ml.) of absolute ethyl alcohol, 190 ml. of sodium-dried benzene and 30 g. (16-5 ml.) of concentrated sulphuric acid for 24 hours. Work up as for Diethyl Adipate and extract the aqueous laj er with ether distil under atmospheric pressure. The yield of ethyl oxalate, b.p. 182-183°, is 57 g. 

Of the common esters, methyl oxalate (solid, m.p. 54°) and ethyl oxalate (liquid) give amides almost immediately upon shaking with concentrated ammonia solution. The resulting oxamide, m.p. 417°, is valueless as a derivative. The esters may, however, be easily hydrolysed and identified as above. 

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. 

Both 2- and 3-methyl groups in pyrido[2,3-Z ]pyrazines are acylated by ethyl oxalate (71TH21500). They give (preferentially 3-) styryl derivatives with aromatic aldehydes and oximes with pentyl nitrite. 

In a 5-I. round-bottom flask fitted with a reflux condenser, a mechanical stirrer (Note i) and a i-l. separatory funnel, is placed 2800 cc. of absolute ethyl alcohol (Note 2), and to this is added 125 g. (5.4 moles) of sodium over a period of one to two hours. The stirrer is started and the mixture allowed to cool to room temperature (Note 3), and a mixture of 730 g. (5 moles) of ethyl oxalate (Note 4) and 290 g. (5 moles) of acetone (Note 5) is added slowly over a period of two to three hours. At first a white precipitate forms this is followed by a yellow precipitate that darkens as the reaction proceeds and later turns yellow again. The temperature rises to about 40. Toward the end the mixture becomes so thick that stirring is difficult. Stirring is continued for one hour after the addition of the oxalate and acetone mixture. The yellow sodium salt is filtered by suction on two 20-cm. Buchner funnels (Note 6). The reaction flask is rinsed with 200 cc. of absolute ethyl alcohol, which is then used to wash the salt. The filtrate is turbid as a rule, but there is not enough sodium salt in suspension or solution to warrant recovery. 

The ethyl oxalate used was dried over calcium chloride for a week (Org. Syn. 2, 23 5, 59). 

Ethyl acetopyruvate has been prepared only by the condensation of ethyl oxalate and acetone in the presence of sodium ethylated The method given above is based on that of Claisen and Stylosd... 

The stirrer is not necessary until the ethyl oxalate is added. The submitters found the use of a nitrogen atmosphere to be unnecessary. 

The ethyl oxalate was redistilled, and the fraction boiling at 106-107°/25 mm. was used. The ethyl succinate was c.p. material obtained from Eimer and Amend and was used without further purification. 

Ethyl oxalylsuccinate has been prepared by the condensation of ethyl oxalate with ethyl succinate in the presence of sodium ethoxide or of potassium ethoxide. The method described above is somewhat more convenient, and has given a higher yield of a better product, than one based upon sodium ethoxide, submitted by A. E. Martell and R. M. Herbst. 

Muconic acid has been obtained in a variety of ways. The procedures that seem most important from a preparative point of view are by treatment of ethyl o ,5-dibromoadipate with alcoholic potassium hydroxide, by condensation of glyoxal (as the sodium bisulfite addition product) with malonic acid, by heating ethyl l-acetoxy-l,4-dihydromuconate (obtained by condensing ethyl oxalate and ethyl crotonate, acetylating, and reducing),and by oxidation of phenol with peracetic acid. ... 

In a i-l. round-bottomed flask fitted with a reflux condenser protected by a calcium chloride tube 46 g. (2 gram atoms) of sodium is dissolved in 600 cc. of absolute alcohol (Note i). About one hour is required for the addition of the sodium, and another hour for its complete solution. Toward the end of the reaction the flask may be heated with a small smoky flame. While the sodium is being dissolved, the following materials are weighed in dry, stoppered containers 58 g. (r mole) of dry acetone (Note 2), 150 g. (1.03 moles) of freshly distilled ethyl oxalate (Org. Syn. Coll. Vol. i, 256), and 160 g. (i.i moles) of ethyl oxalate. 

Natural chelidonic acid is obtained from the herb celandine Chelidonium majus). The synthesis from ethyl oxalate and acetone was first described by Claisen the process was simplified by Willstatter and Pummerer and further improved by Ruzicka and Fornasir.- The present procedure is modelled after that of the last-mentioned investigators. 

Ethyl ethoxalylpropionate has been prepared by the Claisen condensation of ethyl oxalate with ethyl propionate as above, and by the alkylation of ethyl ethoxalylacetate. ... 

During the preparation of the dihalo-(usually dibromo) 20-ketopregnanes, other reactive sites must be protected (e.g., addition of bromine to the A -double bond, ketal formation with a 3-ketone). An elegant method which avoids such problems has been devised by the Upjohn group in their studies on the conversion of 11-ketoprogesterone to hydrocortisone. The former is reacted with ethyl oxalate at C-2 and C-21, then addition of three moles of bromine gives a 2,21,21-tribromide. Alkaline rearrangement produces the side chain unsaturated acid, and the bromine at C-2 is subsequently removed with zinc. 

In a situation where severe steric hindrance e.g., 16,16-dimethyl-20-keto-pregnanes) prevents enol acetate formation, an alternate scheme has been devised. Condensation of ethyl oxalate at C-21 produces, after hydrolysis, the 21-glyoxylic acid this on treatment with acetic anhydride and a strong acid catalyst such as perchloric acid gives both lactone acetates. 

The reactivity of the methylene group adjacent to the lactam group affords the possibility of a Claisen condensation. Thus, treatment of 2-pyrrolidone or 2-piperidone with ethyl oxalate leads to the J -pyrroline-carboxylic (70) and, d -piperideine-2-carboxylic acids (71), respectively. N-methyl lactams furnish N-methyl derivatives (72,73) (Scheme 3). 

The Reissert procedure involves base-catalyzed condensation of an o-nitrotoluene derivative 1 with an ethyl oxalate (2) which is followed by reductive cyclization to an indole-2-carboxylic acid derivative 4, as illustrated below . ... 

Under basic conditions, the o-nitrotoluene (5) undergoes condensation with ethyl oxalate (2) to provide the a-ketoester 6. After hydrolysis of the ester functional group, the nitro moiety in 7 is then reduced to an amino function, which reacts with the carbonyl group to provide the cyclized intermediate 13. Aromatization of 13 by loss of water gives the indole-2-carboxylic acid (9). 

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