Ethyl benzoylformate

The yellowish solution is transferred to a 3-I. round-bottom wide-neck flask and cooled with running water while 300 cc. of concentrated sulfuric acid is added slowly from a separatory funnel. This acidification process requires thirty minutes and the temperature should not rise much above 25 . The liquid froths and about 30 g. of benzoic acid separates but it is not filtered. Extraction of the reaction mixture with 200 cc. portions of ether until 1500 cc. of extract has been collected is now carried out in a separatory funnel. The ether is distilled on a steam bath from a i-l. round-bottom wide-neck flask connected with a water condenser, the extract being added from a separatory funnel as fast as the ether distils. After most of of the ether has been removed, the heating is continued for an additional half hour. 

The crude liquid acid (about 300 g.) is cooled with running water and 15 cc. of concentrated sulfuric acid is added the clear yellow oil becomes cloudy. The acid is esterified by the method described in Org. Syn. 3, 54, with the following changes all three flasks, the alcohol flask, the trap, and the esterification flask are i-l. round-bottom wide-neck flasks. The alcohol flask and the trap are set on adjacent steam baths. The esterification flask is placed in an oil bath which is heated by a free flame. A safety tube leads from the alcohol flask and dips under 7.5 cm. of mercury contained in a side-arm tube. 

This mercury safety valve avoids all dangers which might result from the development of excess pressure within the system (Note 3). The temperature of the esterification mixture is kept at 105-110° and ethyl alcohol vapor is passed through until 500 cc. of distillate has been collected. This requires about three hours. The distillate consists of alcohol, water, and a little ether. 

The crude ester is cooled, an equal volume of benzene is added, then the free acid is neutralized by shaking with about 250 cc. of a 10 per cent solution of sodium carbonate (Note 4). The benzene solution is poured into 1300 cc. of a saturated solution of sodium bisulfite (about 60 g. of technical sodium bisulfite per 100 cc.), contained in a wide-neck bottle equipped with an efficient stirrer, and the mixture stirred for two and a half hours. The mixture soon warms up a little and becomes semi-solid. It is filtered through a 20-cm. Buchner funnel and carefully washed, first with 200 cc. of a saturated solution of sodium bisulfite, finally with two 150-cc. portions of benzene (Notes 5 and 6). The white pearly flakes of the sodium bisulfite addition product are transferred to a 3-I. round-bottom wide-neck flask equipped with a mechanical stirrer and containing 700 cc. of water, 175 cc. of concentrated sulfuric acid, and 500 cc. of benzene. The flask is heated on a steam bath under a hood, the temperature being kept at 55°, and the mixture is stirred for thirty minutes (Note 7). The solution is then poured into a separatory funnel, the benzene separated and the water layer extracted with a 200-cc. portion of benzene. The combined benzene solution is shaken with excess of 10 per cent sodium carbonate solution to remove free acid and sulfur dioxide (Note 8). The benzene is washed with a little water and then dried over anhydrous potassium carbonate (Note 9). The benzene is distilled at ordinary pressure over a free flame from a 500-cc. Claisen flask, the solution being added from a separatory funnel as fast as the benzene distils. It is advisable to distil the ester under reduced pressure although it can be done under ordinary pressure. The fraction distilling around n8°/5mm., 130710 mm., 138715 mm., 148725 mm., 155735 mm., or 

254V760 mm., is collected. The yield of ethyl benzoylformate is 155-175 g. (35-40 per cent of the theoretical amount). (Note 10). 

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The benzene contains 80 g. of impure ethyl benzoate boiling at 180-260° and containing about 20 per cent of ethyl benzoylformate. In the case of the methyl ester the benzene contains 60 g. of impure methyl benzoate, boiling at 170-250°, and containing about 20 per cent of methyl benzoylformate. 

Ethyl benzoylformate has been prepared by the direct esterification of the acid 1 and by the action of oxides of nitrogen on an alcoholic suspension of indigo.2 The acid has been prepared by many different reactions but the most practical are the hydrolysis of benzoyl cyanide,3 the oxidation of acetophenone 4 and the oxidation of mandelic acid.5... 

Table 41.14 Rhodi um-catalyzed hydrogenation of acetophenone (A) and ethyl benzoylformate (B) [105].

In the same study, redox polymers (223) were prepared that contained pendant viologens (Scheme 108). An active reducing agent was obtained by chemical reduction with dithionite or zinc, electrochemically, or by exposure to light. Utilization of the reduced poly(viologen) (224) as an electron transfer mediator was demonstrated by addition of a catalytic amount of the polymer to a mixture of zinc powder, ethyl benzoylformate (225) and water-acetonitrile (1 5). A quantitative yield of ethyl mandelate (226) was obtained after two days at room temperature (Scheme 109). Without the polymer, no reaction was observed after a month. 

The yield of a-keto ester is best when an aromatic Grignard reagent is used, and the reaction is illustrated by the formation of ethyl benzoylformate (Expt 5.174). 

Amino-2-phenylacetamide (192) and ethyl benzoylformate (193) gave 5-hy-droxy-3,6-diphenyl-2(l //)-pyrazinone (194) (EtONa, EtOH, reflux, 5 h 19%).1386 ... 

Scheme 3.10 Asymmetric hydrogenation of ethyl benzoylformate with a rhodacarborane catalyst...

Ethyl benzoylformate has been purified by extraction from benzene with bisulfite solution and regeneration with sulfuric acid. "... 

Several further reports have appeared on the interaction of tervalent phosphorus isocyanates and a-ketocarboxylic esters, giving (22) (see Organophosphorus Chemistry Vol. 7, p. 126 Vol. 8, p. 107) in the case of ethyl benzoylformate, the isomeric compounds (23) and (24 R =Ph, R = C02Et) are also formed, and the... 

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