FORMATION OF HETEROCYCLIC COMPOUNDS. PART 11. 173XV III.---Formation cf Heterocyclic Comapouncls. Part11. Actim of Buses on the ad-Dib,.omo-deu.ivatilcesoj' Certcrin Diccwboxylic Acids.By HENRY ROXDEL LE SUEUR and PAUL HAAS.THE action of diethylaniline on aliphatic compounds containingbromine, and more especially on the esters of a-bromo-monocarboxylicacids (Crossley and Le Sueur, Trans., 1899,75, 161 ; 1900, 77, 83),is to remove the elements of hydrogen bromide with the formation ofthe corresponding unsaturated compound :R*CH,-CHBr*CO,Et --+ R*CH:CH*CO,Et.This action bas been regarded as quite a general one, and holds goodin the majority of instances. I n the case of ethyl aS-dibromoadipate,CO,Et*CHBr*[CH,],*CHBr.CO,Et, a compound in which the twobromine atoms are separated from each other by four carbonatoms, the action of diethylaniline is quite different.Here it is truesmall quantities of the unsaturated ester, ethyl muconate,CO,Et*CH:CH*CH:CH*CO,Et,are formed, but by far the main product of the reaction is ethyl1-phenylpyrrolidine - 2 : 5 - dicarboxylate (Le Sueur, Trans., 1909,95, 2'76) :This reaction involves the fission of the two ethyl groups in diethyl-aniline, a change which is generally not easily effected, but that thisactually takes place was proved by the isolation and identification oflarge quantities of ethyl bromide resulting from the above reaction.The action of aniline is quite similar to that of diethylaniline, asis shown by the action of aniline on methyl a6-dibromoadipate whenthe correspondiag pyrrolidine ester is produced.The usual actionof aniline on compounds of this type is to replace thebromine atom bythe group C,H,*NH :CO,Et*CHBr*[CH,],,*CHBr*CO,Et -+This great tendency for the formation of a five-membered ringis further illustrated by the action of alcoholic potassium hydroxide ona6-dibromoadipic acid, whereby cis-tetrahydrof uran-2 : 5-clicarboxy licacid is produced :CO,Et*CH(NHPh)* [ CHJn*CH(NHPh)* C0,Et.CO,H*CHBr* QH, CH( CO,H)*FK,CO,H* CHBr CH , --3. O<CH(CO,H)*CH,174 LE SUEUR AND HAAS:the usual action of alcoholic potassium hydroxide, namely, theremoval of hydrogen bromide and formation OF the correspondingunsaturated compound, only taking place to a small extent, as onlysmall quantities of muconic acid were obtained.I n contrast to the above reaction, we may compare the action ofalcoholic potassium hydroxide on py-dibromoadipic acid,CO,H=CH,* CHBr CHBr CH,*CO,H,whereby Rupe (Amden, lS90, 256, 1) obtained an 85 per cent.yieldof muconic acid. I n the bromo-acid employed by Rupe, the twobromine atoms are attached to adjacent carbon atoms, and there istherefore no possibility of the formation of a five-membxed ring, andso the action is the norinal one. The constitution of muconic acid wasdiscussed by Rupe, who concluded that i t is correctly expressed by theformula CO,H*CH:CH*CEI:CH*CO,H ; this conclusion is fully con-firmed by the facts that the acid is obtained from as-dibromoadipicacid and tho ethyl ester from ethyl a6dibromoadipate as described inthe present communication,In order to ascertain i f cyclic compounds analogous to ethylI-phenylpyrrolidino-2 : 5-dicarboxylate would be obtained from thecorresponding bromo-derivatives of other dicarboxylic acids, the actionof aniline and monoethylaniline on these bromo-derivatives wasinvestigated.The action of aniline on ethyl up-dibromosuccinate has been alreadystudied by Gorodetzky and Hell (Ber., 1888, 21, 1796), who obtainedethyl up-dianilinosuccinate, CO,Et*CH(NHPh)*CH(NHPh).CO,Et, asthe main product, together with a small quantity of a yellow compoundwhich they were unable to identify.I t was thought that this yellowsubstance might be the desired cyclic compound containing the ringsystem C6H6*N<y but this was found not t o be the case, andthe compound was identified as the anil of anilinomaleic acid,C'(Bischoff and Walden, AnnaZen, 1894, 279, 139).The action of monoethylaniline on ethyl up-dibromosuccinate wasnext investigated, and in this case the compound obtained was ethylbromomaleate, CO,Et*CBr:CH*CO,:Et, which was obtained in a 74.2per cent.yield. Ethyl ae-dibromosebacate was then substituted for ethylap-dibromosuccinate, and heated with aniline, when it was found thatno cyclic compound had beon formed, but that the action had followedthe normal course, and ethyl a8-dianilinosebacate,C0,Et * CH(NHPh)* [ CH,],* CH( N HPh) *CO,E t,was obtained.By heating an aqueous solution of the lactonc of dihydroxybutaneFORMATION OF HETEROCYCLlC COMPOUNDS. PART 11.175totracarboxylic acid, Lean (Trans., 1900, 77,110) obtained two isomerictetrahydrofuran-2 : 5-dicarboxylic acids, which he regarded as cis- andtrans-modifications :H H H H H H H CO,HOne of these acids melted at 1%3-125', and the other, whichmelted at 93--95O, formed a hydrate melting at 63-64', but Leandid not establish which of these acids was the cis- and which the trans-var i e tp.I n a former communication (Le Sueur, Trans., 1908, 93, 716),the preparation and identification of two as-dihydroxyadipic acidsmere described, and it was shown that the as-dihydroxyadipic acidmelting at 174' is the meso-acid, and the one melting at 146' is theracemic variety. Corresponding with these two hydroxyadipic acidsare two a6-dibromoadipic acids; of these, the one melting at192-193' is the meso-acid, and the other, which melts at138-139', is the racemic acid (compare Rosenlem, Bey., 1904, 37,Now, when meso-as-dibromoadipic acid is treated with alcoholicpotash, the tetrahydrofuran-2 : 5-dicarboxylic acid obtained is the onemelting at 124-1 2 5 O , and from stereochemicsl considerations it willbe seen that this must be the &-variety :2090).H H/ H H \ / .. \ CO,H-C-C-- C-C-CO,H -\ H H /Br BrH HI3 ,6--6, HIneso-a&Dibromoadipic acid, cis-Tet~xhydrofuran-2 : 5-di-in. p. 192-193". carboxylic acid, m. p. 124;125".L\ H H /Br BrH HRaceniic a&dibromoadipiu acid,m. p. 138-139".tl.nns-Tetl.aliydroruupsn-2 : 5-di-carboxylic acid, 111.p. 93-95".It might be argued that the meso-dibromoadipic acid undersuch severe treatment as the action of boiling alcoholic potash hadundergone intramolecular change, and that the acid resulting from itwas the trans- and not the cis-form. In order to settle this point176 LE SUEUR AND HAAS:\ H H /an aqueous solution of the meso-as-dihydroxyadipic acid was heatedin a sealed tube, when the acid lost a molecule of water and gave thetetrahydrofuran-2 : 5-dicarboxylic acid meltiug a t 124-125' :meso-as-Dihydrosyadipic acid, cis-Tetrahydrofuran-2 : 5-di-m. p. 174". carbosylic acid,ni. p. 1%4-125".Finally, if the furan acid melting a t 124-125" is really the cis-acid, then it should form an anhydride, whereas the trans-acidwould not.I n order to investigate this point, the acid melting at124-125O was boiled for several hours with an excess of acetylchloride, when an anhydride, C6HG04, was obtained. This anhydride,on treatment with water, readily regenerated the acid melting at134--125O, which proves conclusively that the acetyl chloride has notcaused an intramolecular change, and that the anhydride reallycorresponds with the tetrahydrof uran-2 ; 5-dicarboxylic acid meltingat 124-125', which latter acid must therefore be regarded as the cis-modification.It is interesting t o note that the above anhydride is ieomeric withthe dilactone obtained by heating racemic as-dihydroxyadipic acid(Trans., 1908, 93, 721). Both the anhydride and the dilactone areformed by the l o ~ s of two molecules of water from their respectivedihydroxyadipic acids, the former being formed in two stages : (1) theloss of a molecule of water from two hydroxyl groups ; (2) the loss ofH H HI I HO* &CO,H -c*co---- Iy 2 1 2 -- heatedHO*C*CO,HI IH H Hliieso-a&Dihydrosy- cis-Tetrahydrofuran-2 : 5-di- Anhydride,ndipic acid.carboxylic acid. m. 1). 128-129".H HICO,H*&*OH IXeatedalone 1--Co*c- I I-+ 0 [CH,], 0 __- If--I--- b* CO--( Watery 2 1 2li €!IHO*C-CO,HRscemic as-dihydroxy- Dilactone,adipic acid. m. p. 134"FORMATION OF HETEROCYCLIC COMPOUNDS. PART 11. 177a second molecule of water from two carboxyl groups, whereas thedilactone is formed by the loss of two molecules of water, eachmolecule of water arising from one hydroxyl group and one carboxylgroup.Ex P ERIMENT A L.Action of Diethylaniline on Ethyl a6-Di6romoadipccte.Ten grams of ethyl as-dibromoadipate (m.p. 66') and 16 grams ofrecently distilled diethylaniline were placed together in a flask attachedto a reflux air condenser and containing a thermometer, the upper endof the condenser being connected to a U-tube immersed in a freezingmixture. The flask and contents were gradually heated to lSO', atwhich temperature the reaction began, and were maintained at185-195' for three hours. During the heating a volatile liquid wasevolved, and was condensed in the U-tube; the total amount of esterheated in this manner was 80 grams.The volatile liquid, after being dried, weighed 15 grams, and boiledat 3S-38-5O :0.1514 gave 0 3644 AgBr.Br = 72-87,The liquid was therefore ethyl bromide, the boiling point of whichis 38.37'.The contents of the flask partly solidified on cooling, and mere addedto dilute hydrochloric acid and the whole extracted with ether; theethereal solution was washSd, dried, and evaporated, and the residuedistilled under 29 mm. pressure :165-185 "... ............ 11 *5 grams 230-255" ............... 11.0 gramsThe fraction b. p. 165-185' slowly deposited long, flat crystals,which, after filtration and drying, weighed 3.3 grams, and, aftercrystallisstion from light petroleum (b. p. 40-60°), melted at 63-64',and consisted of ethyl muconate, the melting point of which is quotedas 63-64" by Ruhemann and Blackman (Trans., 1890, 57, 374) :C=60.31 ; H=7.24.C,H5Br requires Br = '73.39 per cent.210-22s ...............3 -0 ) ) 1 Undistilled resid tic?... 13.5 ,,0,1760 gave 0.3892 CO, and 0.1148 H,O.C,,H1,O, requires C = 60.60 ; H = 7.07 per cent.The fraction b. p. 230-255' consisted for the most part of ethyl1-phenylpyrrolidine-2 : 5-dicarboxylate, as was shown by the fact thatit yielded I-phenylpgrrolidine-2 : 5-dicarboxylic acid on hydrolysiswith 10 per cent. alcoholic potash. The acid which was precipitatedon acidifying the hydrolysed product with hydrochloric acid was crys-tallised from a mixture of acetone and light petroleum, from which i tseparated in oblong plates, which decomposed with evolution of gas a t249'. A mixture of equal parts of this substance and I-phenyl-VOL.XCVII. 178 LE SUEUR AND HAAS:pyrrolidine-2 : 5-dicarboxylic acid (Trans., 1909, 95, 277) decomposedat the same temperature :0,1684 gave 8.6 C.C. N, (moist) a t 13' and 764 mm.C1,H,,O,N requires N = 5 -9 6 per cent.The undistilled residue consisted of a dark thick syrup, which, afterbeing kept f o r several months, showed no signs of solidifying, and fromwhich no pure substance could be isolated.N = 6.07.Action of Aniline on Methyl as-Dibromoadipute.Eighteen grams of methyl as-dibromoadipate and 18 grams ofaniline were heated together in a flask immersed in boiling water forforty hours, and the product worked up and distilled as describedunder the action of diethylaniline on ethyl as-dibromoadipate (p. 177).That portion of the distillate boiling at 225-230°/32 mm.weighed8 grams, and solidified on cooling. It was crystallised from lightpetroleum, when it was obtained in needles, which melted at 88' andhad all the properties of methyl 1-phenylpyrrolidine-2 : 5-dicarboxylate(Trans., 1909, 95, 277). A mixture of equal parts of these twosubstances melted a t 88'. When hydrolysed by boiling with 10 percent. alcoholic potash, it gave 1-phenylpyrrolidine-2 : 5-dicarboxylicacid, which decomposed and evolved gas at 252'.Action, of Monoethylaniline on Ethyl ap-Dibromosuccinate.The ethyl dibromosuccinate was prepared by heating succinic acidwith amorphous phosphorus and bromine in a sealed tube and esterify-ing the resulting bromo-acid with concentrated sulphuric acid andalcohol (Gorodetzky and Hell, Ber., 1888, 21, 1729).Twenty grams (1 mol.) of ethyl a@-dibromosuccinate and 15 grams(2 mols.) of monoethylaniline were heated together in boiling waterfor thirty-five hours ; the resulting product, which partly solidified oncooling, was extracted with much ether, and the insoluble residue ofmonoethylaniline hydrobromide filtered off.The ethereal filtrate waswell washed with water, dried, and evaporated, and the residue distilledunder 32 mm. pressure, when the whole distilled between 149' and 152'.It was re-distilled, and a portion boiling at 148-149O collected foranalysis :022125 gave Oa2981 CO, and 0*0838 H,O. C = 38.26 ; H = 4.38.0-1864 ,, 0.1400 AgBr. Br = 32.13.C,H,,O,Br requires C = 38.24 ; H = 4.38 ; Br = 31.87 per cent.The above substance is therefore ethyl monobromomaleate, theboiling point of which is given as 143O/30-40 mm.(Anschiitz, Ber,,1879, 12,2284)FORMATIOR OF HETEROCYCLIC COMPOUNDS. PART 11. 179Twenty grams of ethyl dibromosuccinate gave 11-2 grams of thepure ester, which corresponds with 74.2 per cent. of the theoretical,so that this reaction affords a very convenient method for preparingethyl mono bromomaleat e.The interaction of monoethylaniline and ethyl ap-dibromosuccinatewas tried under various conditions, such as heating together thetwo substances in alcoholic solution ; heating together a t 180--200c,but in all cases ethyl monobromomaleate mas the only substanceobtained.Action of Andine on Ethyl ap-Dihrornosuccinate.Ten grams of ethyl up-dibromosuccinate (1 mol.) and 14 grams(5 mols.) of aniline were heated together for two hours in a flaskimmersed in boiling water, The contents of the flask partly solidifiedon cooling, and were treated with a large volume of ether and thecrystalline solid collected. This solid, which consisted chiefly ofaniline hydrobromide, was treated with 80 C.C.of warm water, thesolution cooled, and the undissolved residue (0.8 gram) collected andcrystaliised from alcohol, when it was obtained in glistening needles,which melted at 149' and had all the properties of ethyl a/?-dianilino-succinate, the melting point of which is given as 150' by Gorodetzkyand Hell (Ber., 1888, 21, 1797).The ethereal filtrate, on evaporation, left a residue which showedsigns of decomposition on attempting to distil it under diminishedpressure j it was therefore not distilled, but alcohol was added to itwhen a yellow solid slowly separated.This solid was repeatedlycrystallised, first from acetone and finally from a mixture of chloro-form and light petroleum, when it was obtained i n small needlesmelting a t 230' :N== 10.29. 0.1224 gave 10.8 C.C. N, (moist) at 1 8 . 6 O and 769 mm.CI6Hl2O2N2 requires N = 10.60 per cent,This yellow solid is insoluble in ether, light petroleum, oralcohol, and moderately soluble in boiling chloroform or acetone ;it is therefore identical with the ariilinomaleic anil,obtained by Bischoff and Walden (Eoc. cit.).The yield of the above yellow solid was very small, and manyattempts were made t o increase it, but without any substantial irn-provement.Among these attempts may be mentioned : (1) additionof anhydrous sodium acetate to the mixture of ester and aniline;(2) the substitution of aniline hydrochloride for aniline; (3) theN 1130 LE SUEUR AND HAAS:interaction of the ester and aniline in alcoholic solution in the cold ;(4) the interaction of the ester and aniline in the presence ofpotassium hydroxide; (5) heating the ester and aniline at 190'.Action of Aniline on Ethyl a0-Dibromosebacate.The ethyl a6-dibromosebacate was prepared by the action of bromineon tho acid chloride of sebacic acid, and esterification of the resultingbromo-acid chloride by the interaction of this substance and alcohol.Twenty grams (1 mol.) of ethyl a6-dibromosebacate and 20 grams(4 mols.) of recently distilled aniline were heated together for elevenhours in a flask immersed in boiling water.The resulting solid wastriturated with dilute hydrochloric acid, and the undissolved solid(4.5 grams) collected and washed with water. The hydrochloric acidsolution was diluted with a large volume of water, when a solid wasprecipitated ; the whole was extracted with ether, the ethereal solu-tion washed, dried, and evaporated, when 12.5 grams of solid residuewere obtained. This was added to the above 4.5 grams of undissoivedresidue, and recrystallised from alcohol untoil the melting point wasconstant :0.1304 gave 7.5 C.C.N, (moist) at 18.5' and 756 mm.Ethyl ae-dianilinosebacate,N = 6.58.C,,H&,N, requires N = 6.36 per cent.C0,Et *CH( NHPh)*[CH,],-CH( NHPh) CO,Et,melts at 119*5-120*5°, and crystallises from alcohol in fern-likeaggregates. It is insoluble in water, sparingly soluble in ether,alcohol, or light petroleum, and readily so in chloroform, benzene, oracetone.The alcoholic mother liquors from which the above ester hadcrystallised gave a substance which, after recrystallisation, melted at94-100', and on analysis gave the following results :0.1680 gave 0.4378 CO, and 0.1342 H,O. C = 71-07 ; H = 8.87.0.1734 ,, 9.7 C.C. W, (moist) at 16' and 764 mm. N=6.55.C,6H,,0,N, requires C = 70-90 ; H = 8.18 ; N = 6.36 per cent.This substance is therefore in all probability stereoisomeric wittithe ethyl ad-dianilinosebacnte melting at 1 19*5-120*5°, butrepeated recrystallisation failed to give a substance with a definitemelting point.a0-Dianilinosebc6cic Acid.-Thirty-three grams of ethyl a0-dia nilino-sebacate were added to a solution of 20 grams of potassium hydroxidein 150 C.C.of alcohol containing a few C.C. of water, and the wholeboiled for fire hours. The resulting solution was concentrated to halfits volume, and gradually added to a boiling solution of 25 C.C. conFORMATION OF HETEROCYCLIC COMPOUNDS. PART 11. 181centrated sulphuric acid in 125 C.C. of water, when the anilino-acidwas precipitated in a granular form. If the precipitation is carriedout in the cold, then the acid separates in an amorphous form, inwhich condition it is difficult to manipulate. The acid was collected,washed with water, dried, and boiled with SO C.C. of alcohol in orderto remove any non-hydrolysed ester, filtered, and after drying weighed23 grams.It was crystallised from amyl alcohol, from which itseparated in spherical aggregates of small needles, which melt andevolve gas at 210-213O :0.1254 gave 0.3180 CO, and 0.0868 H,O. C = 69.15 ; H = 7-69.0.1707 ,, 10-6 C.C. N, (moist) at 18' and 765 mm. N= 7.21.C,,H,,O,W, requires C = 68.75 ; H = 7-29 ; N = 7.29 per cent.a0-Dictnnilinosebacic acid,CO,H*CH(NHPh)* [ CH21,* CH( NHPh)*CO,H,is insoluble in water, alcohol, ether, chloroform, light petroleum,benzene, or ethyl acetate, and only sparingly soluble in boiling amylalcohol.The silver salt was obtained as a white precipitate on adding asolution of the sodium salt of the acid to a solution of silver nitrate ;it darkened somewhat readily on drying :0*1510 gave 0.0536 Ag.Methyl a0-dianilinose bacate,Ag= 35.5.c22E2604N2Ag2 requires Ag = 36.1 per cent.CO,Me*CH(NHPh)*[ CH,],*CH(NHPh)*CO,Me,wa0 prepared by the interaction of aniline and methyl at9-dibromo-sebacate, as described for the preparation of the corresponding ethylester.It is insoluble in water, ether, or light petroleum, readilysoluble in benzene or chloroform, and crystallises from alcohol, inwhich it is sparingly soluble, in fern-like aggregates of needles meltinga t 133-136':0.1334 gave '7.9 C.C. N, (moist) a t 19' and 768 rnm.C24H3204N2 requires N = 6.79 per cent.N = 6-88.Action of Alcoholic Potassium Hydroxide on meso-a8-Dib~omoadipicAcid.The meso-a8-dibromoadipic acid was separated from the mixture ofracemic and meso-a8-dibromoadipic acids obtained by the action ofbromine on the acid chloride of adipic acid (Trans., 1908, 93, 718) hyextracting the mixed acids with water and crystallising the insolubleresidue of the meso-acid from formic acid until its melting point wasconstant (Rosenlew, Ber., 1904, 37, 2090).Seven and a-half grams of meso-as-dibromoadipic acid (m.p182 LE SUEUR AND HAAS:192-193O) were dissolved in 15 C.C. of hot alcohol, and the hot solu-tion gradually added to a boiling solution of 10.5 grams of potassiumhydroxide in 60 C.C.of alcohol, A vigorous reaction immediately set in,and the mixture was boiled on the water-bath for fifteen minutes,then allowed to cool, and filtered (filtrate = A). The insoluble residuewas dissolved in 15 C.C. of water, the solution strongly acidified withconcentrated hydrochloric acid, and, after some time, a crystallineprecipitate separated ; this was collected and dissolved in dilutepotassium hydroxide solution, and again precipitated by hydrochloricacid, when it was obtained in a crystalline form. The substance hadall the properties of muconic acid, and decomposed without meltingat 272' :0.1608 gave 0.2966 CO, and 0.0678 H,O.C,H,O, requires C ;= 50.70 ; H = 4.22 per cent.The aqueous filtrate from the muconic acid was evaporated to asmall bulk, and repeatedly extracted with a large volume of ether.The ethereal solution was evaporated without previous washing ordrying, and the residue dried and crystallised from a mixture of ethylacetate and light petroleum, when it was obtained in nodularaggregates melting at 124-125' :C= 50.30; H = 4-68.0.1434 gave 0.2344 CO, and 0.0684 H,O.C,H,05 requires C = 45.00 ; H = 5.00 per cent.The molecular weight was determined by dissolving the acid inwater and titrating with N/10-sodium hydroxide, using phenolphthaleinas indicator :0.2040 required 25.6 C.C.N/lO-NaOH, which corresponds with aC = 44-58 ; H = 5.30.dibasic acid of M.W. = 159.4.A dibasic acid, C6Hs05, requires M.W. = 160.The substance is therefore cis-tetrahydrofuran-2 : 5-dicarboxylicacid,H HCO,H C0,HIt readily chars when heated above its melting point, and itssolubilities in various solvents correspond exactly with those of thetetrahydrofuran-2 : 5-dicarboxylic acid melting a t 123-1 25" obtainedby Lean (Zoc.cit.).The alcoholic filtrate A (see above) was saturated with carbondioxide, and the precipitated potassium hydrogen carbonate collected.The filtrate was evaporated to dryness, the residue dissolved in a verFORMATION OF HETEROCYCLIC COMPOUNDS. PART 11. 183emall quantity of water, and the resulting solution acidified withhydrochloric acid and repeatedly extracted with a large volume of ether.The ethereal solution on evaporation left a small residue, which, aftercrystallisation from ethyl acetate and light petroleum, melted at 1'74'and had all the properties of meso-ai3-dihydroxyadipic acid (Trans,,1908, 93, 723).The aqueous mother liquors from the ether extracts were mixedand evaporated to dryness ; the residue obtained was dried, extractedwith alcohol, and ths alcoholic solution evaporated and the residuecrystallised from ethyl acetate and light petroleum, when a furthersmall quantity of the tetrahydrofuran acid melting at 124-125Owas obtained.The amount of tetrahydrofuran acid obtained corresponded with28 per cent.of the theoretical, and the yield of muconic acid was only14 per cent. of the theoretical.The anirnonium salt was prepared by dissolving the acid in alcoholand saturating the solution with ammonia, when the salt was pre-cipitated ; it was collected, and crystallised by dissolving in a smallquantity of water and adding alcohol and ether, when it separatedout in long, transparent prisms.It is readily soluble in water,sparingly so in alcohol, and insoluble in ether :0.1231, boiled with NaOH, gave 0.0213 NH,. N= 14.24.C,H60,(NH,), requires N = 14.43 per cent.Anhydride of cis-Tetrahydrofuran-2 : 5-dicnrboxylic Acid.Twenty grams of acetyl chloride and 2.8 grams of cis-tetrahydro-furan-2 : 5-dicarboxylic acid were boiled together for sixteen hours ina flask attached to a reflux condenser. The acetyl chloride wasremoved by evaporation in a vacuum over 50 per cent. potassiumhydroxide solution, and the resulting solid spread on a porous plate,when 2.5 grams of solid, melting at 97-105', were obtained, This,on extraction with 15 C.C.of dry chloroform, left 1.5 grams of residuewhich melted at 122O, and consisted of the unchanged acid. Thechloroform extract, on evaporation in a vacuum, gave 0.6 gram of asolid, which was crystallised from dry chloroform and light petroleum,when it was obtained in slender needles :0.1022 gave 0.1876 C 0 2 and 0,0414 H,O.The anhydride of cis-tetrahydrof uran-2 : 5-dicarboxglic acid,C = 50.1 ; H = 4.5.C6H60, requires C=50*7 ; H=4.2 per cent.readily volatilises when heated, even on the water-bath, and yields a1% FORMATION OF HETEROCYCLIC COMPOUNDS. PART 11.sublimate of long needles, which melt a t 128-129'. It is readilysoluble in ethyl acetate, cbloroforrn, ether, or acetone in the cold, andis insoluble in light petroleum.It slowly dissolves in cold water,giving a strongly acid solution, which on evaporation gives the;original cis-tetrahydrofuran-2 : 5 - dicarboxylic acid melting at124-125'. When the anhydride is heated with resorcinol and afew drops of sulphuric acid, and the product poured into a solution ofpotassium hydroxide, a green, fluorescent solution is obtained.cis-Tetrahydrof wan-2 : 5-dicarbox yldiani Zide,>o, yH,*CH( CO*NHPh)CH,*CH( CO*NHPh)mas prepared by boiling the acid (0.2 gram) with a large excess ofaniline (2 grams) for seven hours. The product mas poured intodilute hydrochloric acid, and the precipitated solid collected, dissolvedin alcohol, and the solution decolorised by animal charcoal.The solidwhich separated out on cooling was crystallised from alcohol, when itwas obtained in small, thick plates, melting and decomposing at208-2099 The dianilide is readily soluble in acetone or chloroformin the cold, sparingly soluble in hot benzene or cold alcohol, andinsoluble in water :N-9.51. 0.1176 gave 9.4 C.C. N, (moist) at 12O and 766 mm.CI8H,,O,N2 requires N = 9.03 per cent.Pormation of cis-Tetrahydrofuran-2 : 5-dicarbozylic Acid frommeso-as-Dihydroxyadipic Acid.One gram of meso-as-dihydroxyadipic acid (m. p. 174O), obtained byhydrolysis of the meso-as-dibromoadipic acid melting at 192-193O(Trans., 1908, 93, 719), was dissolved in 5 C.C. of water, and thesolution heated in a sealed tube for three hours at 200O. The solutionwas filtered to remove a small quantity of black solid, and the filtraterepeatedly extracted with a large volume of ether. The etherealsolution on evaporation left 0.2 gram of solid which, after dryingand crystallisation from ethyl acetate and light petroleum, melted at124-1 25O ; this melting point was unaltered by mixing the substancewith an equal quantity of cis-tetrahydrofuran-2 : 5-dicarboxylic acid.The substance readily charred when heated above its melting point,and its solubilities in various solvents were identical with those of thecis-furan acid.Action of AZcohoZic Potassium Iiydroxide on Racemicas- Dibromoadipic AcidThe action of alcoholic potassium hydroxide on the racemic as-dibromoadipic acid (m. p. 138-1 39') was investigated in the hopTHE HALF-LIFE PERIOD OF RADIUM; A CORRECTION. 185of obtaining the t~ans-tetrahydrofuran-~ : 5-dicarboxylic acid. Themethod of procedure was exactly as described for the action ofalcoholic potassium hydroxide on the meso-dibromoadipic acid, andmuconic acid and a trace of the cis-tetrahydrofuran acid were obtained,together with a small quantity of residue which could not be crystal-lised. No such residue was obtained from the action of alcoholicpotassium hydroxide on the meso-dibromoadipic acid, and i t is notimprobable that this residue did contain some of the trctns-tetrahydro-furan acid, which, on account of its solubility and reluctance tocrystallise (Lean, Zoc. cit.), could not be isolated.CHEMICAL LABORATORY,ST. THOMAS’S HOSPITAL,LONDON, S.E