48 PEHKIN AND THORPE : fl&DIMETEYLGLUTARIC ~I,-$B- Dimethylglutaric Acid und its Derivatives ; Synthesis of cis- and trans- Caronic Acids. By WILLIAM H. PERKIN, jun., and JOCELYN F. THORPE. CARONE, C,,H160, one of the most important ring ketones in the terpene series, is formed when dihydrocarvone hydrobromide is treated with alcoholic potash, hydrogen bromide being eliminated, a decompo- sition which, according to G. Wagner," may be formulated in the following manner. CH- CH, CH* CH, /\ A H2C GO / \ I I H2C H,C CH, = I ( C W , I \ I / \i/ co + HBr. \/ H2C C--CH QH (CHd2CBr CH Dihydrocarvone hydrobromide. Carone. This view of the constitution of carone was considered probable by Baeyer, who, in order to confirm this formula, carried out a number of important experiments on carone, during the course of which he, in conjunction with Ipatieff, investigated the behaviour of this sub- stance on oxidation with permanganate (Bey., 1896, 29, 2796).It was found that, although carone is very stable towards perman- ganate at the ordinary temperature, it is moderately readily oxidised at looo, with formation of two isomeric dibasic acids, C,H,(COOH),, melting at 176' and 2 1 2 O , which were named caronic acids. The former of these, which is produced in much the larger quantity, readily yielded an anhydride melting at 54-56' when boiled with acetyl chloride, but the other acid was not affected by this treatment. * Compare Raeyer (Ber., 1896, 29, 5 and 2796).ACID AND ITS DERIVATIVES. 49 A careful examination of these acids led Baeyer and Ipatieff to the conclusion that the caronic acids were stereoisomeric modifications of dimethyltrimethylenedicarboxylic acid.c(cH3)2 A / \ '('I3[,), /\ COOH. 6-17 -COOH H-Q -C-H, H H COOH bOOH and that these were formed by the oxidation of carone at indicated by the dotted lines in the formula trans-Caronic acid. cis-Caronic acid. CH*CH, the points That these acids have the same structure and are stereoisomeric seemed probable from their behrtviour towards hydrobromic acid at looo, under which conditions both are converted into terebic acid with disruption of the trimethylene ring (Zoc. cit., p. 2801). Br(&CH3)2 GOOH* CH-CH*COOH + HBr = COOH. CH2* CH* COOH (?(cH3)2 + HBr. 0- I = CO CH,. CH* COOH No mention is, however, made of any attempt to convert the one modification into the other.In studying this important work, it seemed to us that it would be most interesting t o find some means of synthesising the caronic acids, and of thus placing their constitution beyond doubt. This was ultimately accomplished in the way described in this paper. Some time since, it was shown by Goodwin and Perkin (Trans., 1896, 69, 1475), that ethylic dimethylacrylate condenses with the sodium derivative of ethylic malonate with formation of ethylic d-imetb y lpropanetricarboxylate, (COOC2H,),CW* C(CH,),* CH,* C00C2H,, and from this, by hydrolysis and elimination of carbon dioxide, pp-di- methylglutaric acid, GOOH* CH2* C(CH,),* CH,* COOH, was prepared. The yield of acid obtained in this way is small, but by substi- VOL. LXXV E50 PERKIN AND THORPE : &?~-DIMETHYLGLUTARRTC tuting ethylic cyanacetate for ebhylic malonate in the condensation with ethylic dimethylacrylate, we now find that the yield of condensation product, which consists of a mixture of some ethylic a-cyano-PP-dimethyG glutarate, COOC,H,* CH(CN)*C(CH,),* CH,.COOC,H,, with much of the hydrogen ethylic salt, COOH. CH(CN)*C(CH,),* CH,. COOC,B ,, is more than 80 per cent. of the theoretical, and, as these ethereal salts, on boiling with 50 per cent. sulphuric acid, are quantitatively converted into PP-dimethylglutaric acid, it is now an easy matter to prepare this acid in quantity. When the anhydride of dimethylglntaric acid is treated with phos- phorus pentabromide and bromine, and the product poured into absolute alcohol, ethylic bromodimethyllglzctarat~, COOC,H,- CHBr* C(CH,),*CH,* COOC,H,, is produced, together with large quantities of the hydrogen ethylic salt of the same acid, COOH.CHBr*C(CH,),* CH,. COOC,H, ; that the latter should be produced in such quantities is certainly remarkable, andra possible explanation of its formation is given in the experi- mental part of this paper. When ethylic bromodimethylglutarate is digested with alcoholic potash, hydrolysis and elimination of hydrogen bromide .takes place simultaneously, and it mixture of acids is ob- tained which, by conversion into the ammonium salts and treatment with alcohol, as recommended by Baeyer and Ipatieff (Zoc. cit., 2978), is easily separated, and found to consist of large quantities of trans- carmic acid, some lactone acid of hydroxydimethylglutaric acid (see below), and traces pf ois-caronic acid.This synthesis of the caronic acids may be represented in the following way. C(CHJ2 /\ gives COOH. UH-CH* COOH. / \ COOC,H,* CHBr OH,* COOC,H5 Hydrogen ethylic bromodimethylglutarate, COOH* CHBr*U(CH,),*CH,* COOC2H5, on treatment with alcoholic potash, is quantitatively converted into trans-caronic acid, apparently without even traces of the cis-modifica- tion being formed. The synthesis of a trimethylene compound in the manner represented above is remarkable, but a few similar cases have been observed, as, for example, in the formation of acetyltrimethylene by the action of alkalis on acetylpropyl bromide, CH,*CO*CH2A(?H2 = UH,* C0*CH<FH2 + HBr. CH,Br CH2 The synthetical caronic acids have been very carefully investigated, and it is shown in the experimental part of this paper that their pro.ACID AND ITS DERIVATIVES, 51 perties agree in a11 respects with those of the acids obtained by Baeyer and Ipatieff from carone, so that there cannot be any doubt as to the identity of the acids produced by these different methods.One additional point of interest has been discovered, namely, 'that tram-caronic acid is converted into the anhydride of ciscaronic acid by the action of acetic anhydride at 220°, a transformation of the tram- into the cia-modification which was required to clearly show that these two acids are stereoisomeric. Furthermore, it is shown in this paper that aqueous sodium car- bonate hydrolyses the hydrogen ethylic salt of bromodimethylglutaric acid, COOH* CHBr*C(CH,),* CH,* COOC,H,, in a manner quite different from alcoholic potash, with formation of the lactone of a-hydroxy- PP-dimethylgh?ark mid, CooH* C'C(CH3)2* CH2, a beautifully c r p b-- 60 talline substance which melts at 112' and is isomeric with the caronic acids.When ethylic bromodimethylglutarafe, COOC,H,* CHBr- C(CH,),* CH,* COOC,HB, is digested with diethylaniline, hydrogen bromide and ethylic bromide are eliminated and an ethereal salt is obtained, which, on examination, has been found to consist of the ethylic salts of tram-caronic acid, and of the lactone of hydroxydimethylglutaric acid. EX PER I M E NTAL. Condensation of Ethyl& DimethyZacryZate with the Xodiuna Derivative of Ethylic Cyanacetate.PP-Dimethylglutaric acid, COOI€*CH,*C(CH,),*CH,* COOH, the acid which is the starting-point in the aynthesis of the caronic aids, was first prepared by Goodwin and Perkin (Trans., 1896, 69, 1476), who obtained it by the following series of reactions. Ethylic dimethylacrylate was, in the first place, digested with the sodium derivative of ethylic malonate in alcoholic solution, when con- densation took place with formation of ethylic dimethylpropanetri- carboxy late, (COOC,H,),CH, + (CH,),C:CH* COOC,H, = (COOC,H,),CH* C( CH,),. CH2-COOC,Hv This ethereal salt, on hydrolysis, yields the corresponding tribarsio acid, which, at 200°, loses carbon dioxide with formation of P/3-dimethyl- glutaric acid, GOOH. CH,* C(CH,),* CH,*COOH, and from this the anhydride is readily prepared by treatment with acetic anhydride.The yield of the original triethylic salt is unfortunately not good, and $ 252 PERKIN AND THOBPE : &~-DIMETHITLGLUTARIC seldom reaches more than 40 per cent. of the theoretical ; indeed, the average yield is scarcely more than 28 per cent. Until quite recently, we have prepared all the dimethylglutaric anhydride required for this research by the method devised by Goodwin and Perkin. A few months since, however, we discovered that the yield may be very greatly im- proved by substituting ethylic cyanacetate for ethylic malonate in the condensation with ethylic dimethylacrylate, the yield of condensation product ,being increased to at least 80 per cent. by this means.* Ethylic a-cyano-#l-dimethylglutarate, COOC2H,: CH(CN)*C(CH,),*CH,* COOC,H,, has been prepared in large quantities by the above proces8, the details of preparation being the following. Sodium (23 grams) is dissolved in alcohol (300 grams), the solution of sodium ethoxide mixed with ethylic cyanacetate (1 13 grams), ethylic dimethyl- acrylate (129 grams) is then added, and the whole heated in a reflux apparatus on the water bath.The sodium derivative of ethylic cyano- acetate, which a t first separates.as a white, crystalline powder, slowly dissolves, and the liquid darkens and gradually sets to an almost solid cake of the sodium derivative of the condensation product, the reaction being finished in about 24 hours. Water is now added, and the oily con- densation product extracted with ether in the usual way; the ethereal solution, after washing with water and drying over calcium chloride, deposits a thick oil which, after two distillations under reduced pres- sure, passes over constantly a t 190' (30 mm.), and consists of pure ethylic cyanodimethylglutarate.0.2614 gave 13.5 C.C. nitrogen at 20' and 750 mm. The yield of this substance produced in the above reaction is about 15 per cent. of the theoretical. The principal product formed in this condensation is the acid ethylic salt of the substance just mentioned, that is, ethylic hydrogen a-cyano-pp- dimeth&Zutwate, COOH- CH(CN) C(CH,),* CH,* COOC,H, ; this is obtained on acidifying the mother liquors of the eondensation product mentioned above and extracting with ether. After thoroughly washing the ethereal solution, drying over calcium chloride and evapo- rating the ether, a thick oil is left, which was not snalysed, since, for reasons stated below, it cannot be purified by distillation, and it showed no signs of crystallising.The yield of this substance formed is no less than 60-70 per cent. of the theoretical. N=5*S0. C12Hl,N0, requires N = 5.81 per cent. * This immensely increased yield is not confined to this condensation, since it has been found that a similar result is obtained when other unsaturated ethereal salts, such as ethylic crotonate, ethylic methylacrylate, &c., are employed, and the products formed in this way are at present being investigated by one of us.ACID AND ITS DERIVATIVES. 53 It is very difficult to understand why this acid ethereal salt should be produced in such large quantities; its formation is certainly not due to the presence of water, as several careful experiments which were made with specially dried alcohol gave, in every case, the same yield, When distilled under ordinary pressures, this acid ethereal salt is readily decomposed, with elimination of carbon dioxide and formation of ethylic y-cyano-P/l-dimethyZhtyrate, CN* CH,* C(CH,),- CH,*COOC,H,, which is a mobile oil distilling without decomposition at 244O.0.2783 gave 21.8 C.C. of nitrogen at 20' and 735 mm. C,H,,O,N requires N = 8-28 pet cent. When digested with concentrated hydrochloric acid in a reflux appa- ratus, it rapidly dissolved, and on cooling and mixing with an equal bulk of water, a mass of crystals separated, which, on examination, was found to consist of the imide of dimethylglutaric acid.N=8*66, This substance is produced by the hydrolysis either of ethylic a-cyanodimeth ylglutarate or hydrogen ethylic cyanodimethylglutarate, the process in the two cases being somewhat differently conducted. When the first or neutral ethylic salt is employed, the pure substance (60 grams) is heated with methyl alcoholic potash (50 grams) for 2 hour#, the solution evaporated until free from alcohol, acidified, and extracted with ether, After evaporating the ether, the residue, which probably consists principally of cyanodimethylglutaric acid, is digested in a reflux apparatus with concentrated hydrochloric acid for 3 hours, when, on evaporating, the whole become4 filled with colourless needles of the imide ; these are collected with the aid of the pump and recrys- tallised from water, In the case of the hydrogen ethylic salt, it is only necessary to boil with an equal volume of concentrated hydro- chloric acid for 3 hours, in order to get directly an almost quantita- tive yield of the imide, care being taken to so moderate the reaction as to avoid loss from the evolution of carbonic anhydride, which is apt to become very vigorous.PP-Dimethylglutarimide crystallises from water in long, colourless needles, which melt a t 144", and a t a higher temperature distil unchanged. It is very sparingly soluble in cold water, readily in hot water, and is almost insoluble in dry ether. 0.3034 gave 26 C.C. nitrogen at 17' and 750 mm. N = 9 *82. C7H,,N02 requires N = 9.93 per cent.58 PERKlN AND THORPE : fl&DIMETB[YLCtLUTARIC This imide is quantitatively converted into PP-dimethylglutaric acid (m.p. 1 0 1 O ) on heating in a closed tube with concentrated hydrochloric acid for 5 hours at 20O0, or by heating with dilute rsulphuric acid (50 per cent.) for 3 hours on a sand bath, the acid being readily obtained from the products of hydrolysis by extraction with ether in the usual may. This anhydride has already been obtained from the acid by treatment with ace& anhydride (Trans., 1896,69,1475), but the process used in the production of the acid and conversion of this into the anhydride has subsequently been much improved, and very large quantities have been prepared for the purposes of this research by the following method, Ethylic cyanodimethylglutarate, as well as the acid ethylic salt, which is always the chief product in the condensation of ethylic cyanoacetate with ethylic dimethylacrylate, are boiled with an equal volume of 50 per cent.sulphuric acid for 12 hours on the sand bath. The exact; end point of the reaction is difficult to determine, owing to the fact that the sulphuric acid converts a large proportion of the dimethyl- glutaric acid into anhydride, and this, like the unhydrolysed ethylic d t ' s , floats on the surface of the aqueous liquid as on oil; we found, however, that 12 hours was sufficient to ensure complete hydrolysis. The product, when cold, is extracted several times with ether, the ether distilled off, and the residue, without further purification, mixed in the same flask with an equal bulk of acetic anhydride, and boiled for 3 hours on a sand bath, using a reflux condenser.After distilling off most of the acetic anhydride under the ordinary pressure, the orude dimethylglutaric anhydride which remains is purified by fractionation under reduced pressure, when almost the whole passes over at 181' (25 mm.) as a colourless oil, which, on cooling, solidifies to a hard, crystalline cake. The yield of pure anhydride obtained in this way was over 90 per cent. of theory calculated from the et hylic cyanodimethylglutarate, or about 73 per cent. calculated from the ethylic cyanoacetate originally used in the condensation. Action of Bromine on Dimetl$gZoctaric Anhydq*ide.--In investigating this reaction, dimethylglutaric anhydride was treated with phosphorus pntsbromide and bromine, and the bromo- or dibromo-acid bromides thus produced were converted into methylic or ethylic salts by the action of methylic or ethylic alcohols.Et h y 1 ic a- b rmo- PP-dime thglgZu t arate, COOC,H,- CHBr*C(CHJ2* CH,- COOC2H5,ACID AND ITS DERIVATIVES. 55 was prepared from dimethylglutaric anhydride (13 grams) by mixing it with phosphorus pentabromide (50 grams), and heating the mixture in a reflax apparatus on the water bath until the reaction was com- plete ; bromine (16 grams) was then gradually added, and a8 soon as the vigorous evolution of hydrogen bromide had ceased the whole was heated on the water bath until colourless, and the product poured into well-cooled absolute alcohol.After being allowed to stand for some hours, water was added, when a heavy oil was precipitated which was extracted with ether, and the ethereal solution, after washing well with sodium carbonate solution, was dried over calcium chloride and evaporated. The nearly colourless heavy oil thus obtained, on fractiona- tion, distilled constantly at 181O (20 mm.), and consisted of pure ethylic bromodimethylglutarate. 0.1820 gave 0.0669 AgBr. Br = 27.23. C1,H,,BrO, requires Br = 27.11 per cent. Hydrogen EthyZic XaZt of a-Bromo-pp-caimethyZgZzctaric Acid, COOH. CHBr*C(CH,),- CH,* COOC,H5. This is precipitated in considerable quantity when hydrochloric acid is added to the sodium carbonate washings obtained as ex- plained in the last paragraph. It is a heavy, colourless oil which distils without decomposition at 240' (35 mm.).0.1932 gave 0.0771 AgBr. C,H,,BrO, requires Br = 29.97 per cent. The formation of this acid ethylic salt in the proportion of about 20 per cent. of the total product of bromination is not due t o the presence of water in the alcohol used, as is shown by the fact that exactly the same amount was formed in an experiment in which extra precautions were taken to eliminate, as far as possible, every trace of water. It seems to us probable that, from the examination of a number of similar cases, some acid bromides have the power of decom- posing alcohol in such a way as to form the free acid and ethylic bromide, thus : R'COBr + HO*C,H, = R*COOH + C,H5Br. It is also possible that the position of the bromine atom may account for the di5culty with which this hydrogen ethylic salt is further etherified, as an experiment which we made with the object of converting the hydrogen ethylic salt into the neutral ethereal salt, by means of alcohol and hydrogen chloride, showed that very little etherifica tion had taken place, Br = 29.80.Methylic a-bromo-PP-~i~ethylgluta~~ate, COOCq* CHBr*C(CH,),* CH,* COOCH,, s obtained when the bromo-acid bromide of dimethylglutaric acid,56 PERKIN AND THORPE : ,!~@-DIMETHYLGLUTARIC prepared as explained above, is poured into well cooled methylio alcohol, It is a mobile liquid boiling at 173' (20 mm.). Laotone of a-Hy&roxy-PP-dimethylglzctccric Acid, COOH*QH* C(CH,),- QH, O--- co This interesting substance, which is isomeric with the caronic acids, was prepared as follows.The hydrogen ethylic salt of bromodimethylglutaric acid (20 grams) wa8 dissolved in dilute sodium carbonate and boiled in a reflux apparatus on a sand bath, care being taken that the solution always had a distinctly alkaline reaction. As soon as a small quantity of the liquid gave no precipitate with hydrochloric acid, the whole was acidified, saturated with ammonium sulphate, and repeatedly extracted with ether ; the dried ethereal solution, when evaporated, gave a hard, crystalline mass which, on being left in contact with porous porcelain for some days, became quite colourless and melted at 80-looo. I n order to purify this crude product, and especially with the object of determining whether it contained any trans-caronic acid (p.59), the lactone was dissolved in a slight excess of ammonia, evaporated on the water bath, and the well dried ammonium salt warmed with absolute alcohol, when the whole dissolved readily, showing that no tram-caronic acid was present. Ether was then added to the alcoholic solution until a slight turbidity wae produced, and the fine, transparent prisms of the pure ammonium salt deposited on standing were collected, washed, and converted into the acid, which was further purified by repeated recrystallisation first from benzene and then from water, Analysis. 0.1643 gave 0.3225 CO, and 0.0932 H,O. C = 53.53 ; H = 6.30. This lactone melts at 112O, and when heated in a small retort distils without change. It is readily soluble in ether, acetone, ethylic acetate, and hot benzene, moderately in chloroform, and almost insoluble in light petroleum.C7H,,0, requires C=53.16 ; H= 6-33 per cent. Action of Alcoholic Potash on Ethylic a-Bromo-&3-dimethylglutwat%. Porrnation of cis- and trans-Caronic Acide. C(CH,), A COOH*CH-CH* COOH. In this interesting experiment, the brom-ethereal salt (1 5 grams) was digested in alcoholic solution with caustic potash (15 grams) forACID AND ITS DERIVATIVES. 57 10 houw, and the product, after being freed from alcohol by evapora- tion on the water bath with the addition of water, was dissolved in water, acidified, and extracted several times with ether. On distilling off the ether, a syrupy mass was obtained, which became partially solid on standing ; this was dissolved in a little water and saturated with hydrogen chloride, when the crystalline solid, which slowly separated after being collected and dried on a porous plate, melted indefinitely between 170° and 200O.This crude substance was dis- solved in ammonia, evaporated to dryness, and the residual solid ammonium salt ground up with cold absolute alcohol; a small quantity passed into solution, but most of it remained undissolved .* The insoluble salt was collected, washed with absolute alcohol, dissolved in a little water, acidified and extracted with ether ; the ethereal solution, on evaporating, deposited a solid acid which even before recrystal€ising melted at 210-21 2O, and after recrystallisiog from water a t 213O. This substance is trans-cmronic acid. The alcoholic filtrate from the insoluble ammonium salt of tram-caronic acid, on being mixed with ether and allowed to stand, deposited a small quantity of crystalline Rolid ; this, after collecting, acidifying, and extracting with ether, yielded an acid melting a t 176O, which, doubt- less, consisted of cis-caronic acid (m.p. 176O), but the quantity was too small for analysis. In this hydrolysis, therefore, both the caronic acids appear to be formed, but the tran8-modification in far larger quantity than the cis-modifi cat ion. On evaporating the solution after the precipitation of the cis- and trans-caronic acids to dryness with ammonia, and dissolving the residue in alcohol, an oily ammonium salt was precipitated on the addition of much ether, which, on long standing, became solid ; from this, on acidifying, a considerable quantity of the lactone of hydroxy- dimethylglutaric acid was obtained, melting a t 112'.Action of Potacsh om the Hydrogen, Ethylic Salt of a-Bromo-PP-dhethpl- glutcvric Acid. This hydrolysis, which gives by far the best yield of trams-caronic acid, was conducted as follows. Equal weights of the brom-ethereal salt and caustic potash were heated together in alcoholic solution in a reflux apparatus for 3 hours, and after evaporating the alcohol, acidifying, and extracting with ether, exactly as explained in the last experiment, a hard, solid, crycltalline cake was obtained; this, on being crystallised once from water, melted at 213O, and consisted of pure trans-caronic acid. On treating this acid and its mother liquors * This salt is th.e acid ammonium salt of trans-csronic acid, and has the formula C,H,,NO, (Baeyer, Ber., 1896, 29, 2800).58 PERKIN AND THORPE : @@-DIMETHYLGLUTARIC with ammonia and alcohol, as explained above, we were not able to extract even traces of the cis-modifioation or of the lactone of hydroxydimethylglutaric acid.It is remarkable that hydrogen ethylic bromodimethylglutarate should behave so differently from the normal ethylic salt on treatment with potash under the same conditions, and that-in the latter case, besides trans-caronic acid and traces of the cis-modification, such con- siderable quantities of the lactone of hydroxydimethylglutaric acid should be produced. The formation of trans-caronic acid from the hydrogen ethylic salt seems to us to prove that this salt has the formula COOH- CHBr-C(CH,),* CH,* COOC,H5, given to it on p.50, and that elimination of hydrogen bromide takes place before hydrolysis. If this ethereal salt had the alternative formula, COOC,H,* CHBr*C(C H,),* CH,* COOH, the elimination of hydrogen bromide would be expected to take place between the bromine atom and the hydrogen atom of the carboxyl group, and the lactone of hydroxydimethylglutaric acid would be formed ; this, however, ia not the case. Action of Diethylaniline on Ethylic BromodimethylgZutcwate.- As it has frequently been found that diethylaniline is a very valuable reagent for removing hydrogen bromide from organic substances, it was thought that interesting results might be obtained if its behaviour were investigated in the present instance.Accordingly, 50 grams of ethylic bromodimethylglutarate was boiled in a reflux apparatus with 75 grams of pure diethylaniline for 2 hours, and after cooling, the nearly solid product was treated with dilute hydrochloric acid, and the oil which separated extracted with ether. The ethereal solution was dried, evaporated, and the residual oil fractionated a great many times, first under reduced and then under the ordinary pressure. It was thus separated into two fractions which boiled at 241' and at about 265-275". The oil boiling at 241', on analysis, gave the following numbers. 0.1345 gave 0.3032 CO, and 0.1087 H,O. C = 61.48 j H = 8.98. C,,H,,O, requires C = 61 -68 ; H = 8.41 per cent. Since this oil, on hydrolysis, yielded tmms-caronic acid, it is evidently the ethereal salt of this acid. The fraction 265-275', which was not analysed, gave, on hydrolysis, the lactone of hydroxydimethylglutaric acid, and is evidently the ethereal salt of this lactonic acid.These two substances were ob- tained in about equal quantities.ACID AND ITS DERLVATIVES. 59 C(CH3h trans-Ccuronic mid, COOH* &)?* COOH. H H The synthetical acid has proper ties identical with those described by Baeyer and Villiger (Bef*., 1896, 29, 2800) as characteristic for the acid from carone. It is sparingly soluble in cold water, but readily in hot water, and separates from its hot solution in prisms which melt at 213O. It is very sparingly soluble in ether, benzene, and cold water, and almost insoluble in chloroform and light petroleum.CvH1,04 requires C = 53.16 ; H = 6-33 per cent. 0.1504 gave 0.2913 CO, and 0.0888 H,O. The silver salt is precipitated as a white, crystalline powder when 0*2660gavo0*2177 CO,, 0*0547H20and0*1538Ag. C = 22.33; H = 2-29; C = 52.82 ; H = 6.56. silver nitrate is added to a neutral solution of the ammonium salt. Ag 3: 57.82. C7H,04Ag, requires C = 22.57 ; H = 2.15 ; Ag = 58.06 per cent. tram-Caronic acid does not give an anhydride when digested with acetic anhydride, but when heated with acetic anhydride at 220' it yields the anhydride of cis-caronic acid (p. 6 1). That it is a saturated acid is shown by the fact that its solution in sodium carbonate does not reduce permanganate. Conversioa of trans-Cwonic Acid into Terebic Acid, 60. CH,* CH- COOH' O--- p%), It was stated in the introduction to this paper that one of the most remarkable reactions of trans- and cis-caronic acid discovered by Baeyer, was the transformation of these acids into terebic acid by the action of hydrobromic acid at looo, and it was consequently of im- portance to show that the synthetical acids behaved in the same manner under the same conditions. About 0.5 gram of pure synthetical tram-caronic acid was heated with about 5 C.C. of concentrated hydrobromic acid (saturated a t Oo) for 5 hours at looo; the hydrobromic acid was then removed by evaporation on the water-bath, and the residue recrystallisedj from water ; the colourless, cubic crystals melting a t 174' thus obtained gave the following numbers on analysis.0.1422 gave 0.2757 CO, and 0.0802 H,O.C = 52.87 ; H = 6.26. C$H1,,O, requires C = 53.16 ; H= 6.33 per cenf,60 ~fl-DIMETEYLCtLUTARIC ACID AND ITS DERIVATIVES. Terebic acid has the same empirical formula and the same melting point as cis-caronic acid, but in other respects these acids possess very different properties, and there can be no doubt that the acid obtained in the above experiment was terebic acid, and not unchanged cis- caronic acid, for the following reasons (compare Baeyer, Ber., 1896, 29, 2799). This acid yields an ammonium salt which differs from the ammonium salt of cis-caronic acid in that, besides having a different crystalline form, its solution in alcohol is not precipitated by ether. It gives, with silver oxide, a silver salt which is readily soluble in water and crystallises in needles, and on boiling with baryta water it yields the characteristic crystalline barium salt of diaterebic acid.Finally, a small quantity heated in a test tube gave the odour of pyroterebic acid, (?(CH3)2 = COOH* OH,* CH:C( CH3), + CO,, O-- bO*CH2* CH* COOH and the residue, dissolved in soda, instantly reduced permanganate, a behaviour not shown by cis-caroniclacid, which, under these conditions, is simply converted into its anhydride, Conversion, of trans-Caronic Acid into cis-Caronic Acid. This conversion, which had not previously been observed, may be readily accomplished in the following way. trans-Caronic acid is mixed with three times its weight of freshly distilled acetic anhydride, and the mixture heated in a sealed tube for 6 hours a t 220'. The dark brown product is then freed from the excess of acetic anhydride by distillation, the residue dissolved in boiling water, digested with animal charcoal, filtered, and evaporated to a small bulk ; on cooling, large, glistening, colourless crystals separate, which melt a t 176', and consist of pure cis-caronic acid.0.1602 gave 0.3108 CO, and 0*0900 H,O. C=52*91 ; H=6*24. C7Hlo04 requires C = 53-16 ; H = 6.33 per cent. / \ cis-Cmonic acid, HC--QH , is very sparingly soluble in cold water, but readily in hot water, and crystallises from water most beautifully in brilliant, glistening plates with bevelled edges. It is sparingly soluble in dry ether and in light petroleum, and practi- cally insoluble in chloroform ; it dissolves readily in sodium carbonate, and this solution does not decolorise permanganate. When heated above its melting point, cis-caronic acid is rapidly ctonverted into it8 6OOH COOHSYNTEESCS OF C@~-TRIMETHY LGLUTARIC ACID, 61 anhydride. The ammonium salt of cia-caronic acid is readily obtained by dissolving the acid in excess of aqueous ammonia and evaporating the solution on a water bath. The crystalline residue differs most sharply from the ammonium salt of the trans-acid in being readily soluble in absolute alcohol ; from its alcoholic solution, it is precipitated by ether in the form of slender needles. When cis-caronic acid is heated with hydrobromic acid, under the conditions given in detail in the corresponding experiment with the truns-acid (p. 59), it is con- verted into terebic acid melting at 174'. It will be seen from this short description of the properties of cis- caronic acid that the synthetical acid is identical with the acid obtained by Baeyer (Zoc. cit.) from carone. /T.*)' Anhydride of cis-Curonic mid, Hq----QH.-This anhydride is Go-0-00 formed either when cis-caronic acid is distilled, or when trans-caronic acid is heated at 220' with acetic anhydride, but it is best prepared by boiling cis-caronic acid with acetyl chloride until hydrochloric acid ceases to be evolved, evaporating, and crystallising the residue from dry ether, when lustrous plates are obtained which melt at 56'. There can be no doubt that this is the anhydride of the &-acid, because it is, as Baeyer found (Zoc. cit., p. 2799), quantitatively con- verted into the acid on boiling with water. The authors wish to state that this research was carried out with the aid of a grant from the Eoyal Society Research Fund, and that they are indebted to Mr. F. H, Lees for making most of the analyses given in this and the succeeding communication. OWENS COLLEGE, M ANCHESTER.