DERIVATIVES OF NORMAL CX LVI. - De riva t ives AND ISO-BUTYRYLPYRUVIC ACIDS. I485 of Normal and iso-Butyivylpyruvic Acids. By ARTHUR LAPWORTH and A. C. OSBORN HANN. THE compounds described in the present communication were prepared during the course of an investigation on theactionof sodium ethoxide and ethyl oxalate on the benzylidene derivatives of certain ketones, a reaction which, in the case of benzylidenemesityl oxide, appeared t o result in the formation of benzaldehyde and oxalyl derivatives, probably of acetone or the original rnesityl oxide. I n order t o obtain further evidence on the point, the interaction of ethyl oxalate and the benzylidene derivatives of some saturated ketones containing the acetyl group was studied, but the experiments did not lead t o the results which were anticipated.The formation of esters of acetylpyruvic acids by the condensation of ketones, containing the acetyl group, with ethyl oxalate has been studied by Claisen and his pupils in the case of acetone, acetophenone, mesityl oxide, &c. (Bey., 1888, 20, 2184, 3189 ; Annulen, 291, 132), and oxalyl derivatives of numerous ketones, esters, and nitriles have been isolated by other chemists. The free ay-diketonic acids obtainable from the ketones of lower molecular weight do not appear to have been prepared, a fact which is perhaps accounted for by the instability of the acids under the conditions which lead t o their formation from the esters, namely, alkaline hydrolysis, as this may result in condensation (Rer., 1890, 22, 3271) or the usual decompositions to which P-diketones are prone.On endeavouring to prepare the free acid from ethyl isobutyryl- pyruvate, me were much struck by the properties of a sparingly soluble compound which was obtained on acidifying the liquid which is formed when the ester is treated with strong potassium hydroxide under certain conditions. Analysis of the compound showed that it contained a small quantity of potassium, and i t was at first supposed to be a condensation product, but further investigation has shown t h a t it is an acid potassium salt containing 1 mol. of potassium isobutyryl- pyruvic acid and 3 mols. of the acid itself. Sodium hydroxide does not yield a similar compound. With normal butyrylpyruvic acid, a sparingly soluble potassium salt is also obtained, but this contains invariably a larger proportion of potassium than in the former instance, and we conclude that it is formed from 1 mol.of the normal salt and 2 mols. of the acid ; as in the first case, the corresponding sodium compound could not be obtained. The properties of these compounds recall the peculiarities of the quadroxalates, and their existence is interesting in the light of1486 LAPWORTH AND HA": DERIVATIVES OF the views expressed byAbegg and Bodlander (Zeit, acnovg. Chem., 1899, 20, 481) as.to the nature of such acid salts, The free acids, obtained by treating solutions of these salts with mineral acids, are very difficult to extract with ether unless the aqueous liquid is first treated with a very considerable proportion of strong sulphuric acid.They could only be isolated as oils, but had all the properties of ay-diketonic acids, whilst the two butyrylpyruvic esters doubtless exist as a mixture of the ketonic and enoEic modifi- cations. We have not yet been able to determine whether ethyl n-butyrylpyruvate is to be represented by the structure CH,E t *CO *CH,*CO*CO,E t, or the alternative one, CH;CO*CHEt~CO*CO,Et, although we believe the former to be the more probable, having regard to the exceptional readiness with which ketones containing the acetyl group afford oxalyl derivatives. EX P E R I M E NT AL. Ethyl isoButyryZpyruwccte, (CH,),CH*UO*CH2*CO*C02*C2H5. A mixture of 20 grams of methyl isopropyl ketone and 40 grams of ethyl oxalate is gradually added to a solution of 5.7 grams of sodium in 70 C.C.of anhydrous alcohol. absolute alcohol " is not sufficiently dry for use in this condensation. The liquid becomes bright yellow in a few moments, and a t the end of two o r three hours sets to a mass of crystals of the sodium derivative of ethyl isobutyryl- pyruvate. The crystals are removed by filtration, washed with a little alcohol, and recrystallised from a mixture of alcohol and ether. The free ester is easily obtained by shaking the sodium compound with dilute hydrochloric acid, and a further quantity may be recovered from the alcoholic mother liquors by shaking these with acidified copper acetate solution and decomposing the resulting crystalline copper derivative. The ester forms a fairly mobile liquid with a faint yellow colour, and may be purified by distillation in a vacuum. It boils with some decomposition a t 230-232' under atmospheric pressure. On analysis : Ordinary 0*3842 gave 0.6067 00, and 0.1954 H,O.C,H,,O, requires C = 58.1 ; H = 705 per cent. The substance shows no signs of crystallising at - 10'. Like other ay-diketonic esters, it dissolves readily in dilute alkalis, yielding solu- tions of a light yellow colour, and forms a number of sparingly soluble metallic derivatives. Dissolved in alcohol, it gives a brilliant, claret-coloured solution on addition of a drop of ferric chloride, It condenses readily with C = 58.3 ; H = 7.6.NORMAL AND ISO-BUTYRYLPYRUVIC ACIDS. 1487 hydrazines, affording sparingly soluble compounds which have not been closely examined. When a drop of piperidine is added to a mixture of the ester and a fatty aldehyde condensation ensues, the temperature rapidly rises, and water separates in a few minutes.The sodium derivative, CyH1304Na, separates from a mixture of alcohol and ether in fine needles. It is somewhat readily soluble in water, b u t less readily so in alcohol, ethyl acetate, acetone, or benzene, and is decomposed by acetic acid forming the free ester. Its solution in water affords characteristic precipitates with solutions of most metallic salts, The crystals probably belong t o the monoclinic system ; in plane polarised light, most of them show oblique extinction; in convergent polarised light, some are seen to have an optic axis emerging perpendicularly through the large faces, and the axial plane is identical with the plane of symmetry.On analysis : 0.1730 gave 0.0588 Nx2S0,. Na= 11.0. C,H,,O,Na requires Na = I1 *O per cent. The copper derivative, (C,H,,O,),Cu, may be obtained from the sodium compound or by shaking the free ester with a saturated solution of copper acetate. It separates from alcohol in bluish-green needles and is soluble in all the usual media with the exception of water. On analysis : Cu= 14.7. (C,H1304),Cu requires Cu = 14.5 per cent. 0.2524 gave 0.0468 CuO. The calcium derivative, (C,H,,O,),Ca, is precipitated in an amorphous form on mixing aqueous solutions of the sodium derivative and calcium chloride. It is practically insoluble in water, but dissolves very readily in ether, ethyl acetate, acetone, or hot alcohol. It separates from the last-named solvent in fine needles.On analysis : 0.3708 gave 0.1272 CaSO,. The barium compound, (CgH1,O,),Bri, closely resembles the calcium 0.2909 gave 0,1344 BaSO,. Ba= 27.2. The cobalt derivati~e,'(C~H~,O,)~Co, is highly characteristic and is formed as a very sparingly soluble yellow precipitate consisting usually of minute needles. It dissolves fairly readily in the usual organic media, and separates in well-formed needles from hot alcohol : Co= 14.1. (C,H130,),Co requires Go = 13.7 per cent. Ca= 10.0. (C9H1,0,),Ca requires Ca = 9.7 per cent. On analysis : derivative in appearance and solubility. (C,H,,O,),Ba requires Ba = 26.9 per cent. 0.3106 gave 0,0594 Co,O,.1488 LAPWORTH AND HA": DERIVATIVES OF The zinc, magnesium, nickel, lead, and aluminium compounds are all sparingly soluble in water, and for the most part crystalline.HydroZgsis.-When ethyl isobutyrylpyruvate is dissolved in excess of somewhat dilute alkali, it is slowly hydrolysed and in thecourse of a few hours addition of a mineral acid causes no precipitate, thus indicat- ing complete hydrolysis; the liquid almost invariably emits an odour of methyl isopropyl ketone, so that the acid formed evidently undergoes further decomposition to a small extent. Extraction of the acidified liquid with organic solvents does not afford any crystalline material, and only a small amount of acid residue is left on evaporating the extracting agent; this may be increased in amount, however, by adding a large excess of strong sulphuric acid to the well-cooled liquid before extraction.Finally, the following method of hydrolysis was employed. The dry sodium derivative of the ester, in amount not exceeding 5 grams, is placed in a mortar, and a 50 per cent. potassium hydroxide solution is added drop by drop while the whole is triturated, until the mixture forms a thick, opaque paste. It is then allowed to remain for not more than one minute (by which time the material has usually assumed the form of a nearly colourless, transparent liquid), diluted with water, and acidified with hydrochloric acid. The liquid deposits a mass of colourless crystals which may be purified by crystallisation from ethyl acetate or by solution in dilute potassium hydroxide and reprecipitation from the filtered liquid by means of hydrochloric acid. The substance melts sharply at 11 1-1 12' ; it is sparingly soluble in cold water, but dissolves readily in dilute alkalis or ammonia.Its aqueous solution is strongly acid and expels carbon dioxide from carbonates. When warmed with water, it is rapidly decomposed, an odour of methyl isopropyl ketone becomes perceptible, and oxalic acid may be detected in the liquid, Its liquid in dilute alkalis has a distinct yellow colour. The crystals of the substance are flat, rhomboidal plates j in con- vergent polarised light,an optic axis of a biaxial figure is seen to emerge obliquely through the large faces. 0.4476 gave 0 0594K,S04. K = 5.9. 0.2651 gave 0.0351 K,SO,. K = 5 9. Three specimens prepared on different occasions were analysed : 0.6482 ,, 0,0856 K,SO,. K = 5.8, C7H,0,K,(C7H,,04), requires K = 5.8 per cent.After admixture with dried and finely divided silica for the purpose 0.1496 gave 0.2771 CO, and 0.0801 H,O. of decomposing any potassium carbonate, (7-50.5 ; H=6.0. C7H,04K,(C7H,,04), requires C = 50.2 ; H = 5.8 per cent.NORMAL AND ISO-BUTPRYLPYKUVIC ACIDS. 1489 Attempts were made to determine the equivalent of the compound by titration against standard sodium hydroxide solution in presence of phenolphthalein; the end reaction, however, was so indefinite as t o render the result worthless. The aqueous solution of the substance gives, on addition of ferric chloride, a deep claret-coloured solution eFactly resembling that which the original ester affords. With copper sulphate, a bright green solution is formed. After neutralisation with cold ammonia, the solution gives no pre- cipitate with calcium chloride until it is boiled, when a copious deposit of calcium oxalate is produced. BenzyZidenemethyZ isoPropyE Xetone, (CH3),CH*GO*CH:CH*C6H5.- A mixture of methyl isopropyl ketone and benzaldehyde in molecular pro- portion, suspended in a 2 per cent.sodium hydroxide solution, is shaken at intervals during a week, and the product afterwards extracted with ether and isolated by fractional distillation under diminished pressure. It boiled with slight decomposition at 284-286' under atmospheric pressure, was an oil with a characteristic odour and showed no tendency t o crystallise at - 15'. On analysis : 0.2476 gave 0.7470 GO, and 0.1770 H20. C,,H,,O requires C = 82.7 ; H = S.0 per cent.The oxinze, C,,H,,ON, was prepared by warming the ketone with dilute alcoholic solution of hydroxylamine hydrochloride and caustic soda, and was precipitated on addition of water as a semi-crystallin'e mass which was purified by crystallisation from light petroleum, It dissolves somewhat readily in the ordinary media with the exception of water, and separates from light petroleum in curved, tooth-shaped crystals which melt at 131-132'. When warmed with dilute hydro- chloric acid, it is rapidly hydrolysed, affording the original benzyl- idene compound boiling at 274-276". C=82*3 ; H= 7.9. On analysis : 0.2268.gave 0.6355 GO, and 0.1690 H,O. C,,H,,ON requires C = 76.2 ; H = 7.9 per cent. The sernicarbazone, C,,H,,:N*NH= CO-NH,, dissolves readily in hot alcohol, acetone, ethyl acetate, benzene, or chloroform, but much less readily in the cold liquids, and is very sparingly soluble in light petrol- eum.It separates from a hot solution in ethyl acetate in the form of rectangular plates or prisms which melt and decompose at 166-167". The substance is easily hydrolysed by means of hot dilute hydrochloric acid. On analysis : C = 76.4 ; H = 8.2. 0.1 787 gave 0.4427 CO, and 0.1 182 H20. C = 67.5 ; H = 7.4. C,,H,70N, requires C = 67.6 ; H = 7.4 per cent. VOL. LXXXI. 5 H1490 DERIVATIVES OF NORMAL AND ISO-BUTYBYLPYRUVIC ACIDS. Eth yZ n-Buty rylpyruvate, CH,* C H, CH, COO CH, CO GO,* C,H, (?) . This substance was prepared from methyl n-propyl ketone by a process exactly similar to that previously employed in making the isomeric ester, but the condensation appears to proceed more slowly than in the latter instance.The ester forms a nearly colourl'ess liquid, which boils and decom- poses at 228-232' under ordinary pressure, and in general exhibits properties which resemble very closely those of the corresponding isobutyryl compound. On analysis : 0,2721 gave 0.5787 00, and 0.1876 H20. CgH1404 requires C = 58.1 ; H = 7-5 per cent. The sodium derivative, C,H,,O,Na, separates from alcohol in long, yellowish needles, and is somewhat readily soluble in water and in most of the ordinary media with the exception of light petroleum. On analysis : C = 58.0 ; H = 7.6. 0.2821 gave 0.0980 Na,S04. C,H,,O,Na requires Na = 11.0 per cent. The copper derivative, ( C,H,,O,),Cu, dissolves in the usual solvents with the exception of water, and forms small, greenish-blue, flattened prisms.Cu= 14.3. (C,HlsO,),Cu requires Cu = 14.5 per cent. Na= 11.3. A specimen crystallised from ethyl acetate was analysed : 0.2705 gave 0.0485 CuO. The calcium and barium derivatives crystallise in white needles from ethyl alcohol. The nickel compound forms pale green needles soluble in ethyl acetate or alcohol ; the cobalt derivative is yellow and crystallises from alcohol. The fmv-ous compound is bluish-purple. Hydrolysis.-When ethyl n-butyrylpyruvate is hydrolysed with strong potassium hydroxide in the mode previously described (p. 1488) and the alkaline liquid is strongly acidified, a sparingly soluble potassium salt is obtained which may be purified by crystallisation from cold ethyl acetate. Unlike the potassium salt of isobutyrylpyruvic acid, however, it forms asbestos-like needles ; these, in polarised light, are seen t o have oblique extinction, the angles varying widely accord- ing to the orientation of the crystals. Three distinct specimens were analysed : 0.7239 gave 0.1188 K,S04. K = 7-4. 0.3493 gave 0.0593 K,SO,. K = 7.6. C7H904K,(C7H,o04), requires K = 716 per cent. C7H,0,K,(CgH1004)1 requires K = 7.6 ; C = 49.2 j H = 5.6 per cent, 0.3647 ,, 0.0640 K2S0,. K = 7.8. 0.2052 gave 0.3676 CO, and 0.1034 H20. C=48.9 ; H=5.6.LAPWORTH AND HA" : MENTHYL PORMYLPHENYLACETATE. 1491 The aqueous solution of the compound, even after neutralisation with ammonia, affords no precipitate with calcium salts until the solution is boiled, when calciunz oxalate is precipitated. On addition of p-nitrophenylhydrazine acetate, a light yellow, microcrystalline precipitate is produced. In general, the chemical properties of this salt closely resemble those of acid potassium isobutyrylpyruvate. CLIEAIICAL DEPARTMENT, T 11 E G 0 LD s M I TH S' INS TIT U T E , NEW CROSS, S.E.