Ethyl propane-1,1,2,3-tetracarboxylate

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 ... 

Tricarballylic acid. Place 228 g. (204 ml.) of ethyl propane-1 1 2 3-tetracarboxylate and 240 ml. of 1 1 hydrochloric acid in a 1-litre threenecked flask, fitted with a mechanical stirrer and a fractionating column with condenser set for downward distillation attach a receiver with side tube to the condenser and connect the side tube to a wash bottle containing water. Boil the mixture, with continual stirring, at such a rate that the... 

The residue is then distilled under reduced pressure, when the ethyl propane-1,1,2,3-tetracarboxylate comes over at i82-i84°/8 mm. The yield is 1261-1273 g. (95-96 per cent of the theoretical amount). 

In a 3-I. flask, fitted with a stirrer and a fractionating column with condenser for downward distillation, are placed 912 g. of ethyl propane-1,1,2,3-tetracarboxylate (p. 29) and 950 cc. of a solution of equal volumes of pure concentrated hydrochloric acid and distilled water. A receiver with a side-tube is attached to the condenser this side-tube leads to a water trap. The mixture is boiled, with continual stirring, at such a rate that the alcohol is removed as fast as it is formed, but without undue removal of water from the flask (Note 1). The progress of the reaction can be followed by noting the rate at which carbon dioxide passes through the trap. When the temperature at the head of the column approaches ioo°, the flame is turned down so that very little liquid distils over. Heating is continued until evolution of carbon dioxide ceases (Note 2). 

In the above reaction one molecular proportion of sodium ethoxide is employed this is Michael s original method for conducting the reaction, which is reversible and particularly so under these conditions, and in certain circumstances may lead to apparently abnormal results. With smaller amounts of sodium alkoxide (1/5 mol or so the so-called catal3rtic method) or in the presence of secondary amines, the equilibrium is usually more on the side of the adduct, and good yields of adducts are frequently obtained. An example of the Michael addition of the latter type is to be found in the formation of ethyl propane-1 1 3 3 tetracarboxylate (II) from formaldehyde and ethyl malonate in the presence of diethylamine. Ethyl methylene-malonate (I) is formed intermediately by the simple Knoevenagel reaction and this Is followed by the Michael addition. Acid hydrolysis of (II) gives glutaric acid (III). 

Ethyl propane-1 1 3 3-tetracarboxylate. Cool a mixture of 320 g. (302 ml.) of redistilled diethyl malonate and 80 g. of 40 per cent, formaldehyde solution ( formalin ) contained in a 1-htre round-bottomed flask to 5° by immersion in ice, and add 5 g. (7 ml.) of diethylamine. Keep the mixture at room temperature for 15 hours and then heat under a reflux condenser on a boiling water bath for 6 hours. Separate the aqueous layer, dry the organic layer with anhydrous magnesium sulphate, and distil under reduced pressure. Collect the ethyl 1 1 3 3-tetracarboxylate at 200-215°/20 mm. The yield is 250 g. 

Ethyl Propane-a,a,y,y-tetracarboxylate.—To a mixture of 1600 g. (10 moles, 1510 cc.) of ethyl malonate (Note 1) and 400 g. of 40 per cent formalin (5.3 moles) in a 5-I. round-bottom flask, cooled to 50 by immersion in ice, is added 25 g. (35 cc.) of diethyl-amine. The mixture is then allowed to come to room temperature and remain for fifteen hours, after which the flask is heated under a reflux condenser on a boiling water bath for six hours. The aqueous layer is then separated, and the residue is distilled under reduced pressure (Note 2) from a 3-I. special Claisen flask (Org. Syn. 1,40). The ester distils at i9o-2oo°/i2 mm.(2io-2i5°/2o mm.) The yield (Note 3) is 1000 g. (61 per cent of the theoretical amount). 

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