518 CROSSLEY AND GlLLTNG: : ACTlON OF ETHYL CYANOACETATELV1.-Action of Eth,yZ Cyanoacetate on 5-chlo~o-1 : 1-By ARTHUR WILLIAM CROSSLEY and CHARLES GILLING (Salters’Fellow).IT has been previously shown (Trans., 1909, 95, 19; Proc., 1909,25, 96) that 5-chloro-l : l-dimethyl-A4-cycZohexen-Sone (I) can becondensed with the sodium derivative of ethyl malonate (or sub-stituted ethyl malonates) to form ethyl 1 : l-dimethyl-A4-~ycZohexen-3-one-5-acetate (11) with elimination of a molecule of ethyl car-bonate :dimethyl- A4-cyclohexen- 3 -one.CMe& CH2-C*>CH B, c c1 + NaCR(C02Et), + EtOH =(1.1CMe,<CH2,C>CH CH *CO + CO(OEt), + NaCl2 1ROCK* C0,Et(11.)These condensation products, on hydrolysis, give rise to a seriesof hydroaromatic ketones according to the following scheme, inwhich R=H, Me, or Et; R,=Me, Et, or Pr:CMe2<gEizg>CH + HOH = CMe2<CHi--q>CH CH -CO + CO, + EtOH.I IR*bH*CO,Et R,It was also mentioned (Zoc.cit., Trans., p. 27) that a smallquantity of a nitrogenous substance, melting at 141°, was alwaysformed together with the condensation products of type 11, due tothe presence of ethyl cyanoacetate in the ethyl malonate employed.In continuance of the investigations on the chemical reactivity ofthe chlorine atom in chlorodimethylcyclohexenone, the latter sub-stance was next condensed with the sodium derivative of ethylcyanoacetate, when the substance melting at 141O is formed inabout 75 per cent. of the theoretical quantity. It gives analyticalnumbers agreeing with the formula C,,H,,O,N, and it was at firstthought that the reaction should be formulated on similar lines tothat taking place between ethyl malonate and chlorodimethylcyclo-hexenone :NaCON 5-CHLORO-I : 1-DIMETHYL-A4--CYCLOHEXEN-3-ONE. 519This assumes that in such reactions ethyl malonate and ethylcyanoacet ate behave as if they possessed similar constitutions.Thechemical properties of the condensation product are not, however,in agreement with those which a substance having formula (111)should exhibit ; for whereas ethyl dimethylcyclohexenoneacetate(11) is it perfectly neutral compound containing a ketonic group,as proved by the fact that it readily forms a semicarbazone, thesolution of the ethyl cyanoacetate condensation product in aqueousalcohol has well-marked acidic properties, may be titrated againststandard sodium hydroxide solution, and the neutral solution soobtained gives a green colour with ferric chloride.Moreover, it canbe readily esterified with ethyl alcohol containing 5 per cent. ofsulphuric acid, giving rise to a mixture of two ethyl derivatives,which can be separated by fractional crystallisation, and since theyboth possess the same general formula, the same molecular weight,and yield the same product on hydrolysis, it seems evident that theyare stereoisomeric substances.In a similar way two stereoisomeric methyl derivatives have beenprepared.The substance melting a t 1 4 1 O cannot be hydrolysed by long-continued boiling with an alcoholic solution of potassium hydroxide,probably on account of the stability of the potassium salt formed,but when heated for an hour with concentrated hydrochloric acid,it is converted into 1 : 1 : 3-trimethyl-A4-cycZohexen-3-one (IV), areaction which may be provisionally represented as follows :CMe,<CH220>CH -+ CMe2<CH,--C>CH CH,*CO -3CH2 yCN* CH* C0,Et HO,C*&H*CO,H *(111.)(IV. 1The marked acidic properties of the condensation product (111)of ethyl cyanoacetate and chlorodimethylcyclohexenone cannot beascribed to the presence of the hydrogen atom attached to the carbonatom, marked with an asterisk, situated between the cyanogen andcarbefhoxyl groups.Por, apart from the extreme ease with whichesterification can be effected, it is found that when either of thetwo ethyl derivatives is boiled for an hour with concentratedhydrochloric acid, hydrolysis takes place, and trimethylcydo-hexenone (IV) is produced; whereas if the conc;titution of theoriginal substance is represented by formula 111, the ethy520 CROSSLEY AND QILLING : ACTION OF ETHYL CYANOACETATEderivative (V) would give on hydrolysis 3-propyl-1 : l-dimethyl-cyclohexen-3-one (VI) :A simple explanation of the acidic properties is forthcoming ifit be assumed that the original condensation product (111) under-goes tautomeric change, the ketonic oxygen becoming enolic, andgiving rise t.0 a substance of formula (VII), which on esterification(etherification) would yield (VIII).CN*CH*CO,Et CN*CH*CO,Et(VII.) (VIII.)I n favour of this supposition is the fact that the substancemelting a t 1 4 1 O forms condensation products with aniline andmonomethylaniline.Whilst formula (111) admits of the formationof a compound with elimination, as water, of the ketonic oxygenwith the two hydrogen atoms of the amino-group in the case ofaniline, it does not admit of an analogous reaction in the case ofmethylaniline; but both reactions are easily explained by theadoption of formula (VII). It will be seen that the ethylderivative (VIII) still shows the presence of a hydrogen atomattached to the carbon atom, situated between the cyanogen andcarbethoxyl groups, and it should therefore be possible to introducea second ethyl group into this position by the successive action ofsodium and ethyl iodide. Although attempts were made to accom-plish this end under a variety of conditions, they were alwaysunsuccessful, and this, taken in conjunction with the fact thatformula (VII) does not offer a ready explanation of the formationof two stereoisomeric modifications of the ethyl and methyl ethers,necessitates some other explanation of the reaction being sought.It has been proposed by J.F. Thorpe (Trans., 1900, 77, 925) thatthe formula which most adequately explains the behaviour of thesodium derivative of ethyl cyanoacetate is (IX), and the mechanismof its condensation with unsaturated substances is as follows :CO,Et*CH:CR, + HC(CN):C<ONa OEt = CO,E t *CH2*CR2*C(CN):C<ONa OEt(IX. 1where R may be either an alkyl group or hydrogen.If, as kindly suggested to us by Dr.J. F. Thorpe, this formulfor ethyl cyanoacetate be applied in the reaction under discussion,the following representation is arrived a t :CH*CO '4'CMe2<CH2*C(OH)>CH t- Or CMe2<CH;-C>CH28( CN) 0 CO,E t E CH,--C(CN)*CO,Et(XI.) (X.)and the product would be ethyl 3-hydroxg-1: l-dimethyl-A3-cyclo-hexenylidene-5-cyanoacetate (XI) (ethyl 1 : l-dintethylcyclohexan-3-onylidene-5-cyanoacetate, X).Such a formula appears to account for all the observed propertiesof the substance, for example, the formation of condensationproducts with aniline and methylaniline ; its marked acidic pro-perties, and the formation of two isomeric methyl and ethylderivatives, which would be represented as cis- and trans-modifica-tions :/\C'0,Et CN/\CN C0,EtThe question naturally arisw, Have the two corresponding cis-and t ram-f orms of ethyl hydroxydimethylcyclohexenylidenecyano-acetate been observed? This isexplained by assuming that the two forms (X) and (XI) aretautomeric, and a hydrogen atom is alternating between the twopositions shown, which would preclude the possibility of fixedisomerism. The introduction of an ethyl group into the moleculecauses the cessation of this mobility of the hydrogen atom, andhence fixed isomerism makes its appearance.This idea correspondswith that advanced by J. F. Thorpe (Trans., 1905, 87, 1669) toaccount for the fact that glutaconic acid cannot be isolated incis- and tram-modifications, whereas its dialkyl derivatives, inwhich the double bond becomes fixed, are capable of existing inthe two forms.We take this opportunity of expressing our cordial thanks toMr.E. C. C. Baly and Dr. Tuck, who have examined ethylhydroxydimethylcyclohexenylidenecyanoacetate and its two isomericethyl ethers spectroscopically, and who have been kind enoue;h tomake the annexed diagram and report.The answer is in the negative522 CROSSLEY AND GILLING: ACTION OF ETHYL CYANOACETATE" The absorption spectra of ethyl hydroxydimethylcyclo-hexenylidenecyanoacetate and its two ethyl ethers were examinedin alcoholic solution, and, as can be seen from the diagram, theyshow very persistent bands. The absorption of the two isomericethyl ethers is identical, and exhibits a band with its head atUscilZation frepwicies.21 26 28 3000 32 34 36 38 4OOo 42 44Ethyl elher (both isomcrides).EthyZ hydroxydimcth~lcyclohe~c?a2/1i~enec~a?~oncetnte.9 9 J ? j # an _ I ._ _ _p T ~ S C ~ L C C of soditma ethoxide1/~=3100. The parent substance shows a band with its head a tl/h=2950, whilst in the presence of sodium ethoxide the bandis shifted to 1 / A = 2700. This shift towards the red, on the additionof alkali, is analogous to the case of dimethyldihydroresorcin, whichtherefore affords evidence that labile tautomerism occurs. Sincethe absorption band of the parent substance is nearer to the reON 5-CHLORO-1: 1-DIMETHY L-A4-CYCLOHEXEN-3-ONE. 523than in the case of the two ethyl ethers, the conclusion may a tonce be drawn that the hydrogen atom of the former is labile, whichexplains why the parent substance cannot be resolved into cis-and trans-modifications.That the shift in the absorption, on theaddition of alkali to the parent substance, is due to the presenceof labile tautomerism is proved by the fact that no change isproduced by the addition of alkali to either of the ethyl ethers.”The following considerations also support the conclusion that thesubstance is ethyl hydroxydimethylcyclohexenylidenecyanoacetate.As already mentioned, when chlorodimethylcyclohexenone is con-densed with ethyl malonate (or substituted ethyl malonates), oneof the carbethoxyl groups is always eliminated as ethyl carbonate(see p. 518). Several instances of the production of the lattersubstance in condensation reactions have been recorded, one ofthe most recent being in the interaction of ethyl sodiocyanoacetateand ethyl 1 -cyanocyclopropane-1-carboxylate :vH2>C(CN)*C0,Et + CN*CHNa*CO,Et + EtOH =CH,and Best and Thorpe (Trans., 1909, 95, 693) consider that theelimination of ethyl carbonate is determined, in all such cases, byspatial considerations.The present experiments lend considerablesupport to this view, for, in the first place, the yields of condensationproducts formed from chlorodimethylcy clohexenone and the sub-stituted ethyl malonates diminished rapidly with increasing mole-cular weight, from which it would appear that the overcrowding inthe molecule, caused by the introduction of heavier alkyl groups,renders the formation of the condensation products more and moredifficult.This affords a possible explanation of the reason for the non-acidity of ethyl dimethylcy clohexenoneacetate (XII) and the acidityof ethyl hydroxydimethylcyclohexenylidenecyanoacetate (XIII), forin the initial product of interaction (XIV) of ethyl malonate andchlorodimethylcyclohexenone, the carbon atom marked * may beregarded as overweighted and the molecule overcrowded in theregion occupied by these groups, with the result that ethyl carbonateis eliminated :CMez<CH2-C>CH CH *CO + EtOH = CMe,<CH2-c>CH CH *CO + CO(OEt),2 1 Hb(CO,Et), H2C*C0,E t(XIV.) (XII.)Why, then, does not a similar elimination of ethyl carbonat524 CROSSLEY AND GILLING : ACTION OF ETHYL CYANOACETATEtake place from the condensation product (XV) formed from ethylcyanoacetate and chlorodimethylcy clohexenone ?C(CN)*CO,EtC(CN)*CO,Et(XIII.)In this case the carbon atom marked * is not so weighted asin the substance with formula (XIV), the CN group being muchlighter than a C0,Et group, and hence the wandering of thehydrogen atom attached to this carbon atom into the ring, withformation of ethyl hydroxydimethylcy clohexen y lidenecyanoacetate(XIII), sufficiently reduces the overcrowding to give a stablesubstance.If, however, this hydrogen atom be replaced by a methyl group.as in the condensation of ethyl methylcyanoacetate and chlorodi-methylcyctohexenone, then the carbon atom * (XVI) is again over-weighted, and as a result ethyl carbonate is eliminated:CMe2<Ca2-c>CH CH -GO + EtOH = CO(OEt), + CMe2<E2zg>CH -+2 1 IMe*c( CN) * C0,Et MW CH-CNjrXVI.) (XVII.) CH,*C(OH)>(33CMe2<CH2- 8 Me*C*ClS(XVIII.)But the product so formed (XVII) is still overcrowded, and ithydrogen atom wanders into the ring, giving hydrozydim8etlbyl-cycloh exenyliden epropionit rile (XVIII).In view of these results, it seemed of interest to examine theinteraction of ethyl acetoacetate and chlorodimethylcyctohexenone,when it was found that the product is the same as when usingethyl malonate, that is, ethyl dimethylcyclohexenoneacetate (XIX).Here also the initial condensation product (XX) contains the over-crowded carbon atom, marked with a, *, and as a consequence theacetyl group attached to it is eliminated, by interaction with ethylalcohol, as ethyl acetate, and a hydrogen atom takes its place.The action of acid hydrolysing agents on ethyl hydroxydimethyl-cyclohexenylidenecyanoacetate can now be easily explained.TheC0,Et group (or the CN group) is first converted into C0,ON 5-CHLORO-1: 1-DIMETHYL-A4-CY CLOHEXEN-3-ONE. 525(XXI), and a t once carbon dioxide is evolved, giving a substanceC M e 2 < ~ ~ : ~ ~ > C H + EtOH =kHAc*CO,Et(XX.)CH,*CO,Et + CMe,<cH2-9>CH CH,*CO~ CH,*CO,Et(XIX.)(XXII) which rearranges itself to dimethylcy clohexenoneaceto-nitrile (XXIII) :--+The CN group in the latter compound is then hydrolysed toCO,H, carbon dioxide is eliminated, and trimethylcyclohexenone(XXIV) produced.The acid hydrolysis of the methyl or ethylethers of ethyl hydroxydimethylcyclohexenylidenecyanoacetate takesplace in a similar way, but the action of alkaline hydrolysing agentson these substances is of quite a different nature. When eitherof the two ethyl ethers is heated with an ethyl-alcoholic solution ofpotassium hydroxide, the carbethoxy-group is attacked, yieldinge th o xydime t hylcycloh exen y lid enrecyanoacet i c acid (XXV) , meltinga t 149O, which acid should exist in cis- and trans-forms, correspond-CMe2<CH~-C/CH CH *C(OEt)+(XXV.)ing with the two ethyl esters. These modifications have not,however, been isolated, as no matter which of the two esters ishydrolysed, one and the same product is obtained; and it can onlybe concluded that, under the influence of the hydrolytic agent, theless stable form of the acid is converted into the more stable form,such cases being common among hydroaromatic substances.When either of the methyl esters of ethyl hydroxydimethylcyclo-hexenylidenecyanoacetate is hydrolysed with methyl-alcoholicpotassium hydroxide, m~ethoxydimethylcyclohexenylidenecyano-a c e t i c a c i d (XXVI), melting at 174O, is produced; but when thehydrolysis of the methyl ethers is carried out in ethyl-alcoholicCN*&CO,526 CROSSLEY AND GILLIKG : ACTION OF ETHYL CYANOACETATEsolution, ethoxydimethylcyclohexenylidenecyanoacetic acid (XXV),melting a t 149O, is formed. The ease with which the methyl groupCMe2<CHi CH *C(OM ')>CHCN-C*C02H(X XVI.)is replaced by ethyl is quite remarkable. An exactly similarphenomenon is observed when either form of ethoxydimethylcyclo-hexenylidenecyanoacetate is hydrolysed with methyl-alcoholicpotassium hydroxide, the ethyl group being replaced by methyl,with production of methoxydimethylcyclohexenylidenecyanoaceticacid, melting at 174O. Such replacements of ethyl by methyl andvice versa in esters have been frequently recorded (compare Purdie,Trans., 1885, 47, 855; 1887, 51, 627; 1888, 53, 391; 1891, 59,468). When ethoxydimethylcyclohexenylidenecyanoacetic acid isheated a few degrees above its melting point, carbon dioxide isevolved, and 3-ethoxg-1: l-dirnethyl-b3-cyclohexenylidene-5-aceto-nitrile (XXVII) is formed:EC M ~ , < ~ ~ * ~ ( ~ ~ ~ > G H -+ C M ~ , < ; ~ ~ + C H~!H=CN bH3(XXVII.Although somewhat stable towards alkalis (see page 532), thisnitrile is readily hydrolysed by acids, with formation of trimethyl-cyclohexenone.EX PER I MENTAL.Forty-eight grams (1 mol.) of chlorodimethylcy clohexenone weregradually added to a mixture of 70 grams (2 mols.) of ethylcyanoacetate and 13-8 grams (2 atoms) of sodium dissolved in 170C.C.of absolute alcohol, when a vigorous reaction a t once commenced,and the liquid turned red. After heating in a water-bath for sixhours, the product was poured into water and extracted four timeswith ether." The aqueous alkaline liquid was then acidified withsulphuric acid, extracted four times with ether, and the etherealsolution washed, dried, and evaporated.The solid residue, weigh-ing 51 grams after drying on porous plate, was purified bycrystallisation, first from benzene, then from aqueous methyl alcohol,and analysed :* On evaporating the ether, a residue was obtained, which was proved to consistprincipally of unchanged ethyl cysnoacetate and a resinous product, which yielded asolid, crystallising from methyl alcohol in fine white needles, melting at 57", but intoo small an amount for complete investigationON 5-CHLORO-1: 1-DIMETHYL-A4-CY CLOHEXEN-3-ONE. 5270-1081 gave 0.2637 CO, and 0.0745 H,O. C=66*53; H=7*66.0.2905 N=5.63.C13H17O3N requires C = 66.38 ; H = 7-23 ; N = 5-95 per cent.Ethyl 3-hydroxy-l : l-dimethyl-A~-cyclohexenylidene-5-cyanoacet-ate, I (ethyl 1 : 1-dim e t hylcycloh exan-3-onylidene-5-cyanoac et at e,,, 13-8 C.C.N, (moist) at 13O and 762 mm.(1.1 (11.)II), is easily soluble in the cold in acetone, chloroform, alcohol, orethyl acetate, and crystallises froin benzene or aqueous methylalcohol in fine white, glistening needles, melting a t 141O. It giveswith ferric chloride in alcoholic solution a fine emerald-greencolour, slowly fading to olive-green, a process which is hastened bywarming, and with ferric chloride in neutral solution it forms adark greeneprecipitate. It has a marked acid reaction in aqueoussolution, and can be titrated with potassium hydroxide solution,when it behaves as a monobasic acid:0.2412 required 10.4 C.C.NI10-KOH. Calculated, 10.3 C.C.Found, M.W. = 232. C13H,,03N requires M.W. = 235.The silver salt, prepared in the usual manner, is a yellow,amorphous precipitate, which darkens rapidly on exposure to airand light:0.2618 gave 0'0828 Ag. Ag=31*62.C,,H,,O,NAg requires Ag = 31.58 per cent.Ethyl 3-anilino-1 : l-dim~thyl-A3-cyclohexenyl~dene-5-acetate, pre-pared by heating ethyl hydroxydimethylcyclohexenylidenecyano-acetate with aniline, is readily soluble in acetone, alcohol, or aceticacid, insoluble or only slightly soluble in light petroleum, benzene,or chloroform, and crystallises from methyl alcohol in felted massesof long, feathery, golden-yellow needles, melting at 197O :02006 gave 14.6 C.C. N, (moist) at 6O and 752 mm.C19H2202N, requires N = 9.03 per cent.Et hy I 3-met hylanilino-l : 1-dim e t h yLA3-cycloh exenylidene-5-c yano-acetate was prepared in a similar manner, using methylanilineN=8-77.instead of aniline.transparent, flattened, yellow crystals, melting at 183O :It separates from methyl alcohol in small28 CROSSLET AND OILLING : ACTION OF ETHYL CYANOACEI'AZ E0.2135 gave 15.2 C.C.N, (moist) a t 8O and 764 mm.C2,,H2402N2 requires N = 8.64 per cent.N=8.64.Hydrolysis of Ethyl Hydroxydin~ethylcyclohexenylidenecyano-acetate.Ten grams of the ester were boiled with 100 C.C. of concentratedhydrochloric acid for six hours, when the solid slowly dissolved andan oil separated. The liquid was then diluted with water, extractedwith ether, the ethereal solution washed, dried, and evaporated, andthe residue distilled under a pressure of 23 mm., when nearly thewhole (5.5 grams) distilled at 100-103°.It possessed the charac-teristic odour of trimethylcyclohexenone (b. p. 109O/32 mm., com-pare Trans., 1909, 95, 24), and its identity with this substance wasestablished by preparing from it the oxime, which melted a t 78O,and the semicarbazone, which melted at 193O (N = 21-55 ; C,,H,,ON,requires N=21.54 per cent.). The melting points of the abovederivatives remained unaltered on mixing with an equal quantityof the corresponding substances prepared in the manner previouslydescribed (Zoc. cit.):Esterification of Ethyl Hydroxydim~ethylcyclohexenylidenecyano-acetate.-1. H7ith Methyl Alcohol and SuZphu~ic Acid.Ten grams of the hydroxy-compound were heated on the water-bath with 100 C.C.of a 5 per cent. solution of sulphuric acid inabsolute alcohol for three hours. The whole was then poured intowater, extracted four times with ether, the ethereal solution washedwith a dilute solution of sodium hydroxide to remove traces ofunesterified material, then with water, dried, and evaporated. Thesolid residue (10 grams) was separated by fractional crystallisationfrom light petroleum (b. p. 60-80O) into two isomeric substancesA and B, melting respectively a t 79O and 90°. No very exactfigures can be given as to the relative proportions in which thesetwo esters are formed, but A predominates, probably to the extentof five to six times the amount of B.Ethyl 3-methoxy-1 : l-dimethyl-A3-cyclohexeny~idene-5-cyanoacet-ate (A) separates out first, crystallising very readily in small,CMe,<CH;-- CHo*c(oM$>cH&CN)*CO,E~white, elongated needles, melting at 79O :0.1255 gave 0.3112 CO, and 0.0869 H,O.C=67*62; H=7.69.C,,H,,O,N requires C = 67.47 ; H = 7.63 per cent.The isomeric ester B is contained in the mother liquors of A, andON 5-CHLORO-1 : I -DIMETHYL-AS-CYCLOIIEXEN-3-ONE. 529after repeated crystallisation, separates in thin, white flakes, meltinga t 90°:0.1486 gave 0.2696 CO, and 0-1022 H,O. C = 67.83 ; H = 7.64.Cl4HI9O3N requires C?= 67.47 ; H = 7.63 per cent.2. With Ethyl Alcohol and Sulphuric Acid.Ten grams of the hydroxy-compound were esterified exactly asdescribed above, using ethyl instead of methyl alcohol, when 12.5grams of a mixture of two esters were obtained, which were separatedby fractional crystallisation from methyl alcohol into two sub-stances, A and B, melting respectively a t 106O and 97O.Therelative proportions produced are much the same as in the case ofthe methyl esters, the isomeric form A predominating in amount.Ethyl ethoxy-1 : l-dintethyl-L\3-~yclohexenylidene - 5 - cyanoacetate(A) crystallises from methyl alcohol in small, white needles, orfrom light petroleum (b. p. 60-80O) in clusters of beautifulelongated, prismatic needles, melting at 106O :0.1280 gave 0-3215 CO, and 0-0958 H20.0.3218The molecular weight was determined by the cryoscopic method,C = 68.60 ; H = 8.31.N=5.53.C15H,,03N requires C = 68-44 ; H = 7.98 ; N =5*32 per cent.,, 15.2 C.C.N, (moist) at loo and 744 mm.using benzene as solvent :Found, M.W. = 235. C15H2103N requires M.W. = 263.This ester has also been prepared by the action of ethyl iodide onthe sodium salt of ethyl hydroxydimethylcyclohexenylidenecyano-acetate in alcoholic and in benzene solution; but the amount ofpure material produced was very small, resinous products beingformed, and under the conditions employed it was not foundpossible t o isolate any of the isomeric ester melting a t 97O.The isomeric ester B, obtained from the mother liquors of A,crystallises from methyl alcohol in lustrous, transparent prisms,melting at 97O:0.1035 gave 0.2606 CO, and 0.0758 H20. C=68-66; H=8*14.The molecular weight, determined by the same method as usedin the case of the isomeric ester, was found to be 236.Although the observed values for the molecular weights of thetwo esters do not show as close an agreement with the theoreticalvalue as might be desired, they are nevertheless of the same order,and serve to prove that the isomerism of these two substances isnot due to the formation of complex molecules, but is in allprobability a case of cis- trans-isomerism.C1SH2103N requires C = 68.44 ; I3 = 7.98 per cent530 CROSSLEY AND GIILLlXG : ACTION OF ETHYL CYANOACETATEHydrolysis of Ethyl Methoxydi~methylcyclohexerzylidenecyarzo-acetate.Experiment showed that the same substance (m.p. 174O) was thesole product obtained when either of the esters, melting respectivelya t 79O and 90°, was hydrolysed with methyl-alcoholic potassiumhydroxide, and therefore, for the purpose of investigating thenature of the substance melting at 174O, there was no object in firstseparating the two esters by the tedious process of fractionalcrystallisation. Four grams of the mixture of thc two isomericesters were therefore heated for two hours on the water-bath with3 grams of potassium hydroxide dissolved in 60 C.C.of absolutemethyl alcohol, when the solution was diluted with water andextracted once with ether, to remove any traces of unaltered ester.The aqueous solution was next acidified with sulphuric acid,extracted three times with ether, and the ethereal solution washed,dried, and evaporated.There resulted 3 grams of a solid, whichwas purified by crystallisation from dilute methyl alcohol, andanalysed :0.1380 gave 0.3318 CO, and 0.0841 H20.Cl2Hl5O3N# requires C = 65.16 ; H= 6.78 per cent.3-Methoxy-l : l-d~m.ethyl-A3-cyclohexenylidene-5-cyanoacetic acid,C= 65-57 ; I3 = 6-77.C( CN) -CO,Hcrystallises from dilute methyl alcohol in masses of irregular plates,melting at 174O. A t 179O a steady evolution of carbon dioxideoccurs, with production of methoxydimethylcyclohexenylideneaceto-nitrile (compare the hydrolysis of the corresponding ethoxy-derivative, p. 531).The presence of a methoxyl group in this acid was confirmed bya Zeisel determination :0.2353 gave 0-2424 AgI. OMe=13*6.C12H1503N requires 'OMe = 14.00 per cent.It is interesting to note that when the hydrolysis of ethylmethoxydimethylcyclohexenylidenecyanoacetate is carried out inethyl-alcoholic solution, the methyl of the methoxyl group isreplaced by an ethyl group, the product being ethoxydimethyl-cyclohexenylideneacetic acid, melting a t 149O (compare p.531).Hydrolysis of Ethyl EthoxydimethyZcyclohexerzyZidenecyanoacetate.The following experiments were carried out both with the esterA, melting at 106O, and with the ester B, melting at 97O, and aON 5-CHLORO-1 : 1-DIMETHYL-A4-CYCLOHEXEN-3-ONE. 531the products of hydrolysis are the same, no matter which of thetwo isomerides is employed, the description of the experimentsapplies to either of them.1. TVith fIpdrochlor.ic ,4cid.-Eight and &half grams of the esterwere heated with 100 C.C.of concentrated hydrochloric acid undera reversed condenser for five hours, when, after extracting withether and working up in the usual way, 5 grams of an oil wereobtained, boiling a t 104-10‘7O/ 25 mm. This fraction was identifiedas trimethylcyclohexenone by preparing from it the semicarbazone,which melted a t 193O, and the oxime, which melted at 77-78O.2. With Potassium Hydroxide.-Twenty-four grams of the esterwere heated for two hours on the water-bath with 15 grams ofpotassium hydroxide dissolved in 200 C.C. of ethyl alcohol (ifmethyl alcohol is employed instead of ethyl alcohol, methoxydi-methylcyclohexenylidenecyanoacetic acid is the product), and theproduct worked up as described in the case of ethyl methoxy-dimethylcyclohexenylidenecyanoacetate (see page 530 j, when a solidwas obtained; which was crystallised from aqueous alcohol andanalysed :0.1114 gave 0.2718 CO, and 0.0731 H20.C = 66.54 ; H = 7.29.0.2009 ,, 9.4 C.C. N2 (moist) at 8O and 752 mm. N=5.59.C,,H170,N requires C = 66-38 ; H = 7-23 ; N = 5-95 per cent.3-Ethoxy-1: l-dimethyZ-L\3-cyclohexenyZ~ene-5-cyanoacet~c acid isreadily soluble in all the ordinary organic solvents, except lightC(CN)*CO,Hpetroleum. It crystallises from aqueous methyl or ethyl alcoholin clusters of minute needles, which melt and decompose a t 149O,gas being steadily evolved a t 153O.The molecular weight was determined by titration againststandard potassium hydroxide solution, using phenolphthalein asindicator :0.1901 required 7.92 C.C.fl/lO-KOH. Calculated, 8.09 C.C.Cl,H170,N requires M.W. = 235. Found, M.W. = 240.3-Ethoxy-1: 1-d~m~et?~y~-A3-cycloTtezenyl~dene-5-aceton~tde was pre-pared by heating 5 grams of ethoxydimethylcy clohexenylidene-cyanoacetic acidmelting point ofVOL. XCVII.under diminished pressure. A little above thethe acid, carbon dioxide was given off, and as532 CROSSLEY AND GILLING : ACTION OF ETHYL CYANOACETATEsoon as the evolution had ceased, the residual liquid was distilled,when the whole (3.7 grams) boiled a t 162--164O/18 mm.:0.2272 gave 13-2 C.C. N, (moist) a t 8O and 768 mm.C,,H170N requires N = 7.32 per cent.The pure substance is a colourless, highly refractive, oily liquid,boiling at 163O/18 mm., and possessing an odour of hydrocyanicacid.A Zeisel determination, carried out according to Perkin'smodified method, gave the following result :N=7-10.0.2468 gave 0.2745 AgI. OEt=21.3.C,,H,,ON requires OEt = 23.5 per cent.This result is somewhat low, but various investigators havefound that ethoxyl determinations generally come out from 1 to2 per cent. below the calculated figure.The nitrile is only very slowly attacked by potassium hydroxidein alcoholic solution, giving a small amount of a substancecrystallising from a mixture of chloroform and light petroleum,melting a t 130°, and giving, on analysis, numbers agreeing with aformula C,,H,,O,N. It is probably, theref ore, hydroxydimethyl-cyclohexenylideneacetamide (I), or, as it is devoid of any acidnature, it may be this substance in the isomeric ketonic form (11).CMe,<zE: C(oH)>CH CMe,<CH;-&w CH *CO(1.1 (11.1When heated with concentrated hydrochloric acid, 8.5 grams ofthe nitrile gave 5 grams of a liquid having a camphoraceous odour,and boiling constantly a t 105O/25 mm. This substance wasidentified as trimethylcyclohexenone by preparing the oxime, whichmelted a t 78O, nor was this melting point lowered by admixturewith an equal quantity of the oxime of pure trimethylcyclo-hex en one .H 8 - co N IT, E HC*CO*NH,Action of Ethyl Methylcyanoacetate on Chlorodimethylcyclo-hexenone.Ethyl methylcyanoacetate was prepared by the interaction ofethyl sodiocyanoacetate and methyl iodide, according to the direc-tions of Auwers (dnnalen, 1895, 285, 283).The product, althoughstated by Auwers to be pure (N = 10.93 ; calculated, 11.02 per cent.),boiled for the most part at 190--195O, and subsequent experimentsshowed that it undoubtedly contained considerable amounts ofethyl cyanoacetate and also ethyl dimethylcyanoacetate, which sub-stances, if present in equivaleut amounts, would account for thecorrect value for nitrogen quoted by AuwersON 5-CHLORO-1 : 1-DIMETHY L-A4-CYCLOHEXEN-3-ONE. 533Twenty-four grams of chlorodimethylcyclohexenone were addedto a mixture of 39 grams (2 mols.) of ethyl methylcyanoacetate and7 grams of sodium (2 atoms) dissolved in 42 C.C. of absolute ethylalcohol. After heating on a water-bath for six hours, the reactionmixture was poured into water, extracted four times with ether(aqueous solution =A), the ethereal solution washed, dried,evaporated, and the residual liquid distilled in a current of steam,when all but a negligible quantity of a sticky resin passed over.The distillate, after extraction with ether, etc., yielded 24 gramsof a liquid, which, after repeated fractionation, gave two mainportions of about equal weight, boiling at 126-127O and190-195O, the latter consisting of ethyl methylcyanoacetate.The fraction 126-12707 from its odour and boiling point,appeared to be ethyl carbonate, and its identity with that substancewas established by analysis :0.1406 gave 0.2629 C02 and 0.1068 H,O.C,H,,03 requires C =50*85 ; H = 8-47 per cent.The above-mentioned aqueous alkaline solution A was acidifiedwith sulphuric acid, extracted with ether, and, after working up inthe usual manner, yielded 32 grams of a viscid, oily liquid, which,after some time, partly solidified.The solid (5 grams) wasseparated by spreading on porous plate, and, after crystallisationfrom benzene, melted at 141°, nor was this melting point alteredon mixing with ethyl hydroxydimethylcyclohexenylidenecyano-acetate (see p. 528). The formation of this ester is undoubtedlydue to the unchanged ethyl cyanoacetate contained in the ethylmethylcyanoacetate employed.The oil, recovered from the porous plate by extraction withether, did not further solidify, and could not be distilled, evenunder diminished pressure, without decomposing.It was theref oreesterified by boiling for four hours with 300 C.C. of ethyl alcoholcontaining 5 per cent. of sulphuric acid. The resulting solutionwas worked up as already described, and the residue (18 grams)distilled under 32 mm. pressure, when the following fractions werecollected :C = 50.99 ; H = 8.44.100-150° = 3.7 grams;170-195O = 6.5 grams;150-170° = 0.4 gram ;195-220° = 2.4 grams.The fraction 100-150° consisted principally of ethyl dimethyl-malonate, for on hydrolysis it yielded dimethylmalonic acid, meltingat 193O with evolution of gas :0.1088 gave 0.1824 CO, and 0.0597 H,O.The presence of ethyl dimethylmalonate proves that the originalC =45*72 ; H = 6-10.C,H,O, requires C = 45.45 ; H = 6-06 per cent.N N 534 CROSSLEY AND GILLING : ACTION OF ETHYL CYAKOACETATEethyl methylcyanoacetate must have contained some ethyl dimethyl-cyanoacetate.The fruction 170-195O, on redistillation, passed over as a paleyellow, refractive, oily liquid, and although it did not boil veryconstantly (170-180°/ 27 mm.), analysis and subsequent hydrolysisproved it to consist of 3-ethoxy-1 : l-dimetl~yl-h3-cyclo~~exen ylidene-5-propionitrile :0.1145 gave 0.3178 C02 and 0.0951 H,O.C,,H,,ON requires C = 76.09 ; H = 9.26 per cent.The mechanism of the reaction giving rise to the correspondinghydroxydimethylcyclohexenylidenepropionitrile has been alreadyexplained (see p.524).Seven grams of the above nitrile were heated with 100 C.C. of con-centrated hydrochloric acid for five hours under a reversed con-denser.The product was poured into water, extracted four timeswith ether, the ethereal solution washed first with sodium hydroxidesolution, then with water, dried, evaporated, and the residue(5 grams) distilled, when it boiled constantly a t 119*5O/25 mm.as a colourless, refractive liquid, which proved to be dimethylethyl-cyclohexenone (compare Trans., 1909, 95, 28), the formation ofwhich substance takes place in accordance with the followingscheme :C = 75.70; H =9.23.CMe,<ci+- CH 'c(0E2>CH -+ CMq<cH, CH2*C(oH) c> CH -+I I C H, 80 CN CH,*C* C 0,HCH, *OH,0.1371 gave 0.3952 CO, and 0.1312 H,O.C,,H,,O requires C = 78.94 ; H = 10.53 per cent.The oxime, prepared in the usual manner, is a viscid, oilyliquid, boiling a t 153O/28 mm., and solidifying on cooling toradiating clusters of flattened, transparent needles, melting at43-45O. It is so readily soluble in all the ordinary organicsolvents that it was found to be most easily purified by distillation:C = 78.61 ; H = 10.63.0.1921 gave 14 C.C.N, (moist) at 18O and 763 mm.Cl,H170N requires N = 8-38 per cent.As this oxime has not been previously described, a specimen waamade for the purpose of comparison from pure dimethglethylcyclo-hexenone, obtained in the manner formerly described (Zoc. cit.).N=8.45ON 5-CHLORO-1: I-DIMETHYL-A4-CYCLOHEXEN-3-ONE. 535It was found to possess properties identical with the above-mentioned oxime.After onecrystallisation from benzene, it melted a t 106O, and proved to beethyl ethoxydimethylcyclohexenylidenecyanoacetate (see page 529).It was mentioned on page 533 that when the aqueous alkalineliquid A was acidified with sulphuric acid, 5 grams of ethylhy droxy dimethylc y clo hexen ylidenecyanoacetat e separated, but evi-dently this separation is not a complete one, and the unalteredmaterial is converted into its ethyl ether (M.p. 1 0 6 O ) during theprocess of esterificatiori to which the residue was submitted.The fraction 195-230° solidified after some time.Action of Ethyl Acetoacetate on Chlol.o~~inetlz?/lcyclo~~exenone.Fifty-two grams (2 mols.) of freshly distilled ethyl acetoacetatewere mixed with a solution of 9.2 grams of sodium (2 atoms) in110 C.C. of absolute alcohol, and 32 grams (1 mol.) of chloro-dimethylcyclohexenone added. The resulting red liquid wastransferred to two soda-water bottles, which were securely corked,and then heated in a boiling-water bath fof two hours. Thereaction mixture was poured into water, extracted five times withether, and the ethereal solution washed, dried, and fractionated,using a Young’s rod-and-disk still-head. When the ether hadpassed over, a small quantity of a liquid boiling a t 65-70°(residue = A) was obtained, which, after further purification, wasproved to consist of ethyl acetate,The residue A was distilled in a current of steam to removeunaltered ethyl acetoacetate, and the non-volatile portion extractedthree times with ether, the ethereal solution dried and evaporated,and the residue distilled, when nearly the whole (18 grams) passedover a t 181°/27 mm.:0.1242 gave 0.3106 CO, and 0.0972 H20. C = 68.20 ; H = 8.69.C,zH1803 requires C = 68-57 ; H = 8.57 per cent.These numbers indicated that the substance was ethyl 1: 1-di-methyl-AacycZohexen-3-oned-acetate (Trans., 1909, 95, 23), and theidentity of the two liquids was established by hydrolysing the aboveproduct with alcoholic potassium hydroxide (Zoc. cit.), when ityielded trimethylcycZohexen-3-one, boiling a t 9 9 O / 18 mm., charac-terised by the preparation of its oxime, which melted a t 77-78O.The authors take this opportunity of expressing their thanks tothe Research Fund Committee of the Chemical Society for a grantwhich has, in part, defrayed the expenses of this investigation.RESEARCH LABORATORY, PHARMACEUTICAL SOCIETY,17, BLOOMSBURY SQUARE, W.C