THE CONDENSATION OF ETHYL ACETOACETATE ETC. 137 XV1.- The Conderbsation of Elhyl Acetoacetate with p-Dirnethylaminobeiualdehyde and Ammonia. By LEONARD ERIC HINKEL and HERBERT WILLIAM CREMER. THIS work was interrupted by the war and as there seems no possibility of it being continued jointly it was considered advisable to place on record such results as were obtained. The investigation arose from a desire t~ study the influence of substituent groups in aliphatic and aromatic aldehydes in Hantzsch’s pyridine condensa-tion. It was thought that the introduction of basic groups would retard it and for this purpose p-dimethylaminobenzaldehyde waa chosen. The condensation was found to take place very slowly even on heating the best results being obtained by allowing the mixture to remain for about one hour a t the ordinary temperature and then heating under pressure for seven to nine hours.The yield of the dihydro-derivative could not be increased by longer heating o r by employing excess of ammonia. The viscous filtrate from the dihydro-compound was subjected to steam distillation but no aldehyde passed over with the steam. The filtrate was soluble in hydrochloric acid and reprecipitated unchanged by alkali. I n all probability the filtrate contained a cyclo-ketone formed by the further condensation of the 1 5-diketone first produced along with the dihydrecompound. The filtrate was not further examined. The dihydro-derivative can also be produced by condensing the aldehyde with ethyl acetoacetate (1 mol.) and ethyl &amino-crotonate (1 mol.).This method was also employed with pdimethylaminobenzaldehyde and also for comparison with benzaldehyde. In the first case the yield was 21.7 per cent., whilst with benzaldehyde it was more than 90 per cent. showing in a striking manner the effect of the p-dimethylamino-group on the condensation. The oxidation of the dihydro-derivative could not be carried out according to the usual method by nitrous fumea. Even at low temperatures brown needle-shaped crystals readily VOL. CXVII. 138 HINEEL AND CREMER THE CONDENSATION OF ETHYL formed which were found to be p-nitrosodimethylaniline nitrate. The readiness with which the p-dimethylaminophenyl group is eliminated is probably due to the influence exerted by the dimethyl-amino-group since it has been shown (Schiff and Puliti Ber.1883, 16 160; Epstein Annulen 1885 231 1) that phenyl- and styryl-dimethyldihydropyridinedicarboxylic esters are readily oxidised by nitrous fumes without elimination of the phenyl or styryl groups. EXPERIMENTAL. E t h y 1 4-p- Dimet h y Zantinophenyl-2 6-dimet h y Z-1 4-dihydro-pyridine-3 5-dicarboxylate, CM6-- NH--CMe CO,Et *E C H ( C6H,*NMe2).;C;'* CO,Et A mixture of 30 grams (1 mol.) of p-dimet.hylaminobenz-aldehyde 52 grams (2 mols.) of ethyl acetoacetate 3.4 grams ( 1 mol.) of ammonia and 70 C.C. of alcohol contqained in a closed flask was allowed to remain for an hour and then heated for nine hours over a rapidly boiling water-bath. Considerable pressure was developed in the flask which was therefore suitably protected against explosion.On cooling about half of the contents of the flask crystalliseld and the crystals were collected and washed with a small quantity of alcohol. The residue was evaporated over a water-bath until viscid and when cold diluted with an equal volume of alcohol; on stirring a small further quantity was obtained the total yield being 40 grams or 53-7 per cent. of the theoretical. The crude yellow crystals were1 purified by crystal-lisations from alcohol acetone and ethyl acetate and were obt'ained finally in nearly colourless fine needles melting a t 158'5O: 0.2452 gave 0.6047 CO and 0.1702 H,O. 0.1617 , 10.8 C.C. N (moist) a t 7-5O and 750 mm. N,=8.0. The ester is very similar to the trimethyl ester prepared by Hantzsch. It is stable to boiling dilute alkali and boiling alcoholic potassium hydroxide slowly acts on it bringing about complete decomposition.When heated witlh concentrated hydrochloric, sulphuric or phosphoric acid the compound is also decomposed, with the elimination of two molecular proportions of carbon dioxide. By virtue of the dimethylamino-group however it possesses basic properties and readily forms sparingly soluble additive compounds with hydrogen chloride and with methyl iodide. C=67.26; H=7-7. C,,H,,O,N requires C = 67-64 ; H = 7.52 ; N = 7-52 per cent ACETOACETATE WITH P-DDIETHYLAMINOBENZALDEHYDE ETC. 139 UorLclerLsatiom of p-Dimethyluminob enzaldehyde Ethyl 9 ceto-ace tat e and Et h y I &,4 minocrotonat e . A mixture of 6 grams (1 mol.) of p-dimethylaminobenzaldehyde, 5-2 grams (1 mol.) of ethyl acetoacetate and 4-5 grams (1 mol.) of ethyl /3-aminocrotonate was heated a t 120° for several hours.After two days the viscous mass was dissolved in an equal volume of hot alcohol and left to crystallise. The product after recrystal-lisation from ethyl acetate was identical with the ester just described the yield being 3'2 grams or 21.7 per cent. of the theoretical. The hydrochloride C2,H,,04N,,HC1 prepared by dissolving the substance in dilute hydrochloric acid separates as a fine white, crystalline powder especially on dilution with water. It was washed with water and alcohol and dried in a vacuum: 0.1827 gave 0-4130 C O and 0.1257 H,O. C=61.6; H=7-63. 0.1613 , 9-4 C.C. N (moist) a t 14O and 751 mm. N=6*85.0.1466 , 0.0527 AgCl. Cl=8.60. C,,H,04N,,HC1 requires C = 61-68 ; H = 7.09 ; N = 6.85 ; C1=8.68 per cent. It melts a t 201° and when heated above its melting point, rapidly decomposes yielding dimethylaniline among the products. Met hiodide C,,H,0,N2,CH31 .-A mixture of the substance with excess of methyl iodide in acetone solution was gently heated for a short time over a water-bat.h. The clear hot liquid was then poured into an evaporating basin and stirred with a glass rod until the mass solidified. The crude methiodide was washed with acetone and purified by crystallisation from hot acetone and finally from ethyl acetate. It melts a t 182-183O: 0.1532 gave 0.2892 CO and 0.897 H,O. C=51*48; H=6*50. C,,H,80,N,,CH31 requires C = 51.36 ; H = 6-05 ; 1 = 24.7 per cent.0.2052 , 0.0952 AgI. 1=25*06. Ethtyl 4-p-Bimethylam.inopheny1-2 6dimethylpyrdine-dicarb oxylate. A mixture of 37.3 grams of the dihydro-ester and 3.2 grams of sublimed sulphur was gently heated at 150O. The mixture melted, and hydrogen sulphide was rapidly evolved the heating being con-tinued until the liquid became clear and free from gas bubbles. When cold the mass solidified and wils dissolved in boiling alcohol, from which it crystallised on cooling. The crude crystals were freed from any uncombined sulphur by dissolving them in excess a 140 QOODSON CONSTITUENTS OF THE of dilute hydrochloric acid and filtering. The ester was precipi-tated as a white flocculent mass from the acid solution by means of sodium carbonate solution. It was washed with water and re-crystallised from alcohol and finally from light petroleum.The yield was almost quantitative. The ester is readily soluble in benzene ether chlorof o m or hot alcohol sparingly so in warm light petroleum and melts at 124-5O: 0.1853 gave 7.65 C.C. N (moist) a t 3O and 778 mm. C,,H,0,N2 require5 N = 7.57 per cent.. HydroZysis.-Fifteen grams of the ester were mixed with 30 grams of potassium hydroxide dissolved in 100 C.C. of alcohol and the mixture was heated to boiling under a reflux condenser for several hours. On cooling the potassium salt separated out in fine crystals which were collected and quickly washed with a little absolute alcohol and dried in a vacuum. A further yield was obtained from the filtrate on concentration. The potassium saltl is yellow and very deliquescent in air changing to a deep yellow mags. It is sparingly soluble in boiling alcohpl. The neutral aqueous solution is deep yellow but the addition of either acid or alkali instantly destroys the colour which can however be restored by the careful neutralisation of the excess of acid or alkali. N=7-65. CHEMICAL DEPARTMENT, KING’S COLLEGE, LONDON. [Received November 23rd 1919.