Ethyl oxalate, reactions

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°. 

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. 

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. 

A thioamide of isonicotinic acid has also shown tuberculostatic activity in the clinic. The additional substitution on the pyridine ring precludes its preparation from simple starting materials. Reaction of ethyl methyl ketone with ethyl oxalate leads to the ester-diketone, 12 (shown as its enol). Condensation of this with cyanoacetamide gives the substituted pyridone, 13, which contains both the ethyl and carboxyl groups in the desired position. The nitrile group is then excised by means of decarboxylative hydrolysis. Treatment of the pyridone (14) with phosphorus oxychloride converts that compound (after exposure to ethanol to take the acid chloride to the ester) to the chloro-pyridine, 15. The halogen is then removed by catalytic reduction (16). The ester at the 4 position is converted to the desired functionality by successive conversion to the amide (17), dehydration to the nitrile (18), and finally addition of hydrogen sulfide. There is thus obtained ethionamide (19)... 

Alkylation of the dihydroxyacetophenone, 44, with epichloro-hydrin results in condensation of two molecules of the phenol with the latent glycerol (45). Reaction of the intermediate with ethyl oxalate affords the chromone ester, 46. Saponification leads to the bronchiodilator cromoglycic acid (47). The agent is usually administered by oral insufflation as its extremely insoluble disodium salt. 

Ethyl Propianyl-Pyruvate 36 grams of methyl ethyl ketone and 73 grams of ethyl oxalate are condensed in the presence of sodium ethylate, the reaction mixture being refluxed in an alcoholic medium. 28 grams of the desired product having a boiling point of 100° to 105°C/6 mm are obtained. 

Ester Condensation.—In a i-l. round-bottomed flask fitted with a reflux condenser equipped with a dropping funnel and a calcium chloride tube is placed a suspension of 6.1 g. (0.27 mole) of powdered sodium (Note 1) in 150 cc. of absolute ether. A solution of 12.6 g. (0.27 mole) of absolute ethyl alcohol (Note 2) and 50 cc. of absolute ether is added, and the mixture allowed to stand overnight to complete the reaction. To the suspension of sodium ethylate, 57 g. (0.39 mole) of ethyl oxalate (Org. Syn. Coll. Vol. 1, 256), diluted with 50 cc. of ether, is added in portions. After the spontaneous reaction subsides, the pale... 

Ethyl benzoylacetate has been prepared by the condensation (by means of sodium ethylate) of ethyl acetate with ethyl benzoate,1 acetophenone with ethyl carbonate,2 and acetophenone with ethyl oxalate, with subsequent heating 3 by treatment of ethyl phenylpropiolate4 or a-bromocinnamic acid 5 with concentrated sulfuric acid, and of ethyl diazoacetate with benzalde-hyde 6 by the condensation of benzene with the monoethyl ester of malonyl monoacid chloride and aluminum chloride,7 of benzoyl chloride with the product of the reaction of magnesium and ethyl chloroacetate in ether,8 of alcohol on benzoylacetimino ethyl... 

Ethylene carbonate, reaction with potassium thiocyanate, 42, 59 Ethylene sulfide, 42, S9 Ethyl formate, reaction with cyclo-hexylamine, 41, 14 Ethyl- -hexylamine, 43, 47 5-(2-Ethylhexyl)-l,2,3,4,5-pentachloro-cyclopentadiene, 43, 93 Ethylhydrazinium hydrogen oxalate,... 

The only known reaction of compound 79 is its reaction with ethanol leading to ethyl oxalate and 3,5-dibenzoyloxadiazole 80 (Scheme 19). Although the structure of 80 was proven both by 13C NMR and by comparison... 

Condensations with alkyl nitrites and nitrates, however, are not so generally applicable as the true ethyl acetoacetate reaction, and the possibility is not excluded that they proceed in another way compounds with mobile hydrogen might first he added to the inorganic part of the ester by means of an aldol condensation. The fact that fluorene, which contains no active double bond at all, combines with ethyl nitrate (as well as with ethyl oxalate) and sodium ethoxide in the same way, yielding oci-nitrofluorene, seems to support this second theory (W. Wislicenus). 

Hofmann amine separation org chem A technique to separate a mixture of primary, secondary, and tertiary amines they are heated with ethyl oxalate there is no reaction with tertiary amines, primary amines form a diamide, and the secondary amines form a monoamide when the reaction mixture is distilled, the mixture is separated into components. haf-mon am,en, sep-3,ra-sh3n ... 

In order to activate the 21 position to halogenation, it is hrst converted to an oxalate. Condensation of the triketone with ethyl oxalate in the presence of alkoxide proceeds preferentially at the 21 position to give (12-2) due to the well-known enhanced reactivity of methyl ketones. Reaction of the crude sodium enolate with bromine leads to the dibromide (12-3), the oxalate moiety being cleaved under the reaction conditions. The Favorskii rearrangement is then used to, in effect, oxidize the 17 position so as to provide a site for the future hydroxyl group. Thus, treatment of (12-3) with an excess of sodium methoxide hrst provides an anion at the 17 position (12-4). This then cyclizes to the transient cyclopropanone (12-5)... 

The above reactions have been illustrated for 2- and 4-alkylpyridines. They generally fail if no heteroatom is a or 7, as in 3-alkylpyridines and 5-alkylpyrimidines. a- and [3-Alkyl groups in pyridine A-oxides are somewhat more reactive than those on the corresponding pyridines. In addition to the reactions already mentioned, 2-picoline 1-oxide undergoes Claisen condensation with ethyl oxalate to yield the pyruvic ester (630) (for the conversion of alkyl substituents in A-oxides into CH,OAc groups see Section 3.2.3.12.5.iv). 

The reaction probably occurs via the acylation of the biguanide followed by cyclization (Scheme 54). The mechanism of the reaction between ethyl oxalate and cyclohexylbiguanide... 

Aryl cyanates react with ammonia to form the bis(iminoethers) (100). These compounds form 1,3,5-triazines by reaction with a further equivalent of the cyanate (Scheme 58) (67AG(E)206). IV-Amidoamidines condense with ethyl oxalate to form 2-amino-1,3,5-triazines (equation 53) (71CPB1789). 

In a 3-I. round-bottom flask, fitted with a reflux condenser, is placed 650 cc. of absolute alcohol (Org. Syn. 5, 56) and to it 46 g. (2 moles) of sodium is added as rapidly as possible without loss of material through the condenser. If all the sodium does not dissolve, heat is applied. To the hot sodium ethylate solution 312 g. (2.1 moles) of ethyl oxalate (Org. Syn. 2, 23 5, 59) is added as rapidly as possible. Then, immediately, 234 g. (2 moles) of benzyl cyanide (Org. Syn. 2, 9) is added. The reaction mixture is allowed to stand overnight. The solution is transferred to a 3-I. beaker and treated with 250-300 cc. of water (Note 1). It is then warmed to 350, and made strongly acid to litmus with concentrated hydrochloric acid. Mechanical stirring is used during the acidification. On cooling to ordinary... 

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... 

To a suspension of 23 g (1.0 mole) of sodium pellets in 800 ml of absolute ether was added 80 ml of a mixture of 86 g (1.0 mole) of y-butyrolactone and 146 g (1.0 mole) of ethyl oxalate. The reaction mixture began to boil gently and was allowed to reflux spontaneously for two hours, after which time the remainder of the butyrolactone and ethyl oxalate mixture was added... 

Harringtonine (107) has been synthesized 170) by the method shown in Scheme 59. Claisen condensation between 283 and ethyl oxalate in the presence of NaH gave 284 which, when heated under reflux with aqueous HC1, was converted to a mixture from which the oxide (285) was isolated. Without purification, 285 was treated with HCl/MeOH to yield 286, saponification of which yielded the unsaturated acid as its sodium salt 287. After conversion to the acid chloride, reaction with cephalotaxine yielded 288. 

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