1298 BONE AND SPRANKLING: RESEARCHES ON THE CXXIV. -Researches on the Alkyl-substituted Succinic Acids. Part III. Dissociation Constants. By WILLIAM A. BONE and CHARLES H. (2. SPRANRLING. IN our last communication (this vol., 654), we showed that the two isopropyl groups in cis- s-diisopropy lsuccinic acid have an extra- ordinary influence upon its dissociation constant, and in discussing the constants of alkyl-substituted succinic acids as a class, we ex-ALKYL-SUBSTITUTED SUCCINIC ACIDS. PART 111. 1299 pressed the opinion that the data then available were not suficient to justify our making any very definite statement as to the factors which determine the magnitudes of the constants in this particular series. The experiments recorded in the present paper, we hope, will go some way towards supplying this deficiency, and, together with previous results, will provide an adequate basis of fact for the discussion of a very difficult question.I n the first place, it seemed desirable to ascertain whether other ' is0 ' groupings have an influence upon the dissociation constant of a succinic acid in any way comparable with that of the two isopropyl groups in cis-s-diisopropylsuccinic acid. We therefore investigated the hitherto unknown s-diisobutylsuccinic acids from this standpoint, and also determined the constants of several new aal-diaIkyl- and tri- alkyl-succinic acids which seemed likely to afford evidence directly bearing on the question a t issue. A full discussion of these and pre- vious results will be found at the end of the paper.A. s-D i i s o but y 1s u c c inic A c i d s. The preparation of these acids involved the following operations : (1.) The preparation of isobutylacetic acid from ethyl malonate and isobutyl bromide, (2.) The bromination of isobutylacetic acid by the Hell-Volhard- Zelinsky method, (3.) The preparation of ethyl P-isobutylcyanosuccinate by the in- teraction of ethyl a-bromoisobutylacetate and the sodium derivative of e thy1 cyanoace t a t e, (4.) The isobutylation of ethyl P-isobutylcyanosuccinate, and the subsequent hydrolysis of the ethyl ap-diisobutylcyanosuccinate so ob- tained. We will briefly describe the later stages of the preparation. Ethyl P-isobutylcyanosuccinate was obtained by heating an alcoholic solution of the sodinm derivative of ethylcyanoacetate with the calcu- lated quantity of ethyI a-bromoisobutylacetate in soda-water bottles to 100' for 24 hours, the details being similar t o those given for the preparation of ethyl PP-dimethylcyanosuccinate (Trans,, 1899, 75, 854).The yield of refractionated oil was 65 per cent. of that theoret- ically possible, it was nearly colourless, had a density d 0'/4' 1.0455, and a refractive index pNa 1.4408. On analysis : 0,1902 gave 0,4253 CO, and 0.1439 H,O. 0.2926 ,, C = 60.99 ; H= 8.41. 14-15 C.C. nitrogen a t 14' and '746 mrn. N=5.71. C,,H2,0,N requires c1= 61.1'7 ; H = S.23 ; N = 5.59 per cent. In order to prove the constitution of the oil, a portion of it was1300 BONE AND SPRANKLING: RESEARCHES ON THE hydrolysed with concentrated hydrochloric acid, when an acid melting at 1079 and in all other respects identical with isobutylsuccinic acid, was obtained.The acid was analysed with the following results : 0,2021 gave 0.4085 CO, and 0.1490 H,O. 0,1329 of the silver salt gave on ignition 0.0739 Ag. C,H,,04Ag, ,, Ag = 55.68 per cent. C=55.11 ; H=8.19. Ag=55*59. C,H,,O, requires C = 55.17 ; H = 8.04 per cent. Ethyl ap-diiso6utyZcyanosuccilzd e was prepared by heating molecular proportions of the sodium derivative of ethyl P-isobutylcyanosuccinate and isobutyl bromide with alcohol in soda-water bottles a t 100' for 24 hours. As the liquid still remained alkaline, more isobutyl bromide was added and the process continued for a second period of 24 hours. The product, isolated in the usual manner, was twice fractionated under reduced pressure. The refractionated oil was very viscous and nearly colourIess ; it boiled at 187-189' under 20 mm.pressure, had a density d 0°/4' 1.0128, and a refractive index pNa 1,4462. On analysis : 0.2103 gave 0.5036 CO, and 0.1790 H,O. 0.2199 ,, 8.7 C.C. nitrogen at 21' and 754 mm. N =4*69. C = 65.31 ; H = 9.46. CI7H2,O,N requires C = 65.59 ; H = 9-32 ; N = 4.50 per cent. The oil mas hydrolysed in two stages, namely, first with alcoholic potash (1 hour) in order to obtain the ap-diisobutylcyanosuccinic acid, which was then boiled for 36 hours with 50 per cent. sulphuric acid on the sand-bath (compare bhis vol., 659). Oily particles of the anhydride of cis-s-diisobutylsuccinic acid separated out during the process, and on cooling crystah of the trans-isomeride appeared in the liquid.The whole was a t once submitted to steam distillation, when the cis-anhydride passed over as a colourless oil, leaving the trans-acid behind ; the separation of the two isomerides was complete. The cis-acid was obtained from the aqueous distillate, and the trams-acid from the residual liquid exactly as described in our previous paper (Zoc. cit., 661). cis-s-DiisobzLtylsuccinic acid is very sparingly soluble in water, and after two or three recrystallisations from that solvent melts a t 97-98'. On analysis : 0.1935 gave 0.4419 CO, and 0.1633 H,O. 0,1867 of the silver salt gave on ignition 0.0907 Ag. C,,H,,O,Ag, ,, Ag = 48.66 per cent. C = 62.30 ; H = 9.38. Ag = 48.57. C12H2204 requires C = 62.60 ; H = 9.56 per cent. The anhydride of this acid, obtained in the usual manner, was a colourless oil boiling at 280-286' under atmospheric pressure ;ALKYL-SUBSTITUTED SUCCINIC ACIDS.PART III. 1 301 with aniline, i t yielded a Ziyuid anilic acid, resembling in this par- ticular cis-s-diisopropylsuccinic acid. The sparingly soluble calcium salt had the composition C,, H,o0,Ca,3H,0. trans-s-Diisobutylswccinic A cid-The crude acid obtained on ex- tracting the residual liquor in the distillation flask melted at 170-180', but after two or three recrystallisations from a mixture of benzene and light petroleum it melted a t 193-195'. That it was now quite free from the cis-isomeride was shown by the fact that treatment with cold acetyl chloride had no effect on its melting point. On analysis : 0.1516 gave 0.3475 CO, and 0.1356 H,O.0.2020 of the silver salt gave on ignition 0.0982 Ag. C = 62.49 ; H = 9.94. Ag = 48.61. C,,H220, requires C -- 62.60 ; H = 9.56 per cent. C,,H200,Ag2 ,, Ag = 48.66 per cent. The acid dissolves on being heated with acetyl chloride, forming a liquid anhydride which, with water, yields the original acid again, and with aniline, a solid anilic acid melting a t 234-135'. Conversion of the trans- into tZle cis-Acid.-The trans-acid is quantitatively converted into the cis-isomeride by heating it in a sealed tube with acetyl chloride or acetic anhydride a t 180', and subsequently converting the cis-anhydride so formed into the acid. On the other hand, we have not been able to effect even a partial conversion of the cis- into the trans-acid, although we heated it in a sealed tube with concentrated hydrochloric acid at 230" for 24 hours.cis-s-Diisoproyylsuccinic acid, we have shown, undergoes no alteration on being heated with hydrochloric acid to 180°, but a t 220-230' is to a very small extent converted into the ti-ans-form. Evidently cis-s-diisobutylsuccinic acid is a still more stable substance. Dissociation Constants.*-The s-diisobutylsuccinic acids are so spar- ingly soluble in water that in neither case were we able to obtain a solution containing the gram-molecule in less than 600 litres. It was therefore necessary to apply a correction for the resistance of the water in each case. The following are the corrected values obtained : cis-s-Diiso6wtylswccinic acid. 21. P V . m. 100k.668.5 157.0 0.45 10 0.0555 1337.0 198-0 0.5648 0.0548 2674.0 241 -5 0.6900 0.0574 K = 0*056. * The determinations of these and all other dissociation constants included in this and our two previous papers were made at a temperature of 25".1302 BONE AND SPRANKLING: RESEARCHES ON THE trans-s-l)iiso62ctyluzLccinic ucicl. V. PV. m. 100k. 1060 134.5 09843 0.0226 2120 172.2 0,4920 0.0224 4240 2 14.5 0.6135 0.0232 These numbers indicate that the two isobutyl groups have no such extraordinary influence on the constant of a succinic acid as the two isopropyl groups have in the case of cis-s-isopropylsuccinic acid. K = 0.0225. B. aal-Me t h y Jpr op y l s u c cini c A c i d s . Ethyl ~ - m e t h y Z - a - ~ o ~ y I c y a n o s u c c ~ ~ c ~ t ~ was prepared by heating an al- coholic solution of the sodium compound of ethyl p-met hylcyanosuccinate (compare Trans., 1899, '75,853) with the calculated quantity of propyl iodide on the water-bath in a reflux apparatus until the liquid became neutral (45 mins.).The propylated oil was extracted as usual and twice refractionated. The yield was 81 per cent, of that theoretically possible. The oil boiled a t 169-171O under 24 mm. pressure, had a density d 0'/4' 1.0501 and a refractive index pNa 1.4428. On analysis : 0.2077 gave 0.4647 CO, and 0.1591 H,O. 0.3122 ,, 15.3 C.C. nitrogen at 19' and 766 mm. N=5*68. C13H2,04N requires C = 61-17 ; H = 8.23 ; N = 5.59 per cent. It was hydrolysed in two stages and the resulting cis- and trans-aal- methylpropylsuccinic acids were separated by steam distillation as described in the preceeding section of this paper.cis-aa-l-Methyl~opyZsucci~ic acid is fairly soluble in water and is best recrystallised from warm benzene. It melts at 92-93', On analysis : C = 61.01 ; H = 8-51. 0,1726 gave 0.3486 CO, and 0.1269 H,O. 0.1 163 of the silver salt on ignition gave 0,0648 Ag. C,H1204Ag, ,, Ag = 55.68 per cent. C=55.09 ; H= 8.17. Ag = 55.70. C,H,,O, requires C = 55.1 7 ; H = 8-04 per cent. The acid gave a liquid anhydride which, with aniline, yielded an anilic acid melting a t 82-84', trans-aa,-Met~yZ~op~lszLcciltic acid is less soluble in water than the cis-isomeride, and after two or three recrystallisations from a mixture of benzene and light petroleum, melts at 158-160'. On analysis : C=55*02; H=8*26. 0.2219 gave 0.447'7 GO, and 0.1659 H,O.0.1972 of the silver salt on ignition gave O o l l O O Ag. C,H,,O,Ag, ,, Ag = 55-68 per cent. Ag=55*78. C,H,,O, requires C = 55.17 ; H= 8.04 per cent.ALRYL-SUBSTITUTED SUCCINIC ACIDS, PART III. 1303 The acid gradually dissolved in warm acetyl chloride forming a liquid anhydride which with water yielded the original acid again, and with aniline an anilic acid melting a t 166-167'. Mutual Conversion of cis- and trans-Acids.-( 1) On heating the cis- acid in a sealed tube with strong hydrochloric acid for 8 hours, a partial conversion into the trans-isomeride occurred. The resulting mixture melted indefinitely between 130' and 150°, and was subse- quently resolved into two portions melting at 92' and 156-158' respectively. (2) The trans-acid was quantitatively converted into the cis-anhy- dride on being heated in a sealed tube with acetic anhydride t o 180" for 6 hours.Dissociation constants.-The following are the values obtained : V. 26.5 53.0 106.0 212.0 V. 55.0 110.0 220.0 440.0 cis-aa,-Methylpropylsuccinic acid. 28.39 0*0Sll 39-18 0.1119 53.31 0.1560 74.70 0-2 135 PV. 112. K= 0.0271. trans-aa,- Methylpropylsuccinic acid. PW. m. 44.42 0.1272 61.04 0.1774 82.03 0.2344 110.3 0.3152 K = 0.0335. 100k. 0.0270 0.0267 0.0272 0,0273 100k. 0.0336 0.0334 0.0333 0.0330 C. aa,-Met?L ylisobuty Zsuccinic Acids. The preparation of these acids from ethyl P-methylcyanosuccinate is so similar to that of the acids already described, that it is hardly necessary for us to give any detailed account of it.Ethyl P-methyl-a-isobutylcyanosuccinate is a colourless oil boiling at 186-188' under 35 mm. pressure, having a density d 0'/4' 1.0528 and a refractive index pNa 1.4446. The two isomeric methylisobutylsuccinic acids obtained on hydro- lysing this oil have properties so similar t,o those of the acids described in the preceding section that we may simply tabulate them as follows : M. p. M. p. Acid. Anhydride. Anilic acid. i!rans-aal-Methylisobutylsuccinic . . . 133' liquid 132--133 cis )) 9 ) ... 88-90' ,, 94-96'I304 BONE AND SPRANKLING : RESEARCHES ON THE Dissociation constccnts.-The following are the values obtained : 21. 34.5 69.0 138.0 276.0 9. 88.9 177.8 355-6 711.2 cis-aa,-MethylisobutylszL.ccin~c acid. 40.08 0-1145 55.73 0.1592 75.18 0.21 48 101.0 0.2885 P V * m.K= 0'0427. trans-aa,-Methylisobutylszcccinic ucid . PV* 592. 47.28 0.1351 64.43 0.1841 87-45 0.2498 116.10 0.3318 K= 0,0236. 100k. 0,0429 0.0427 0.0426 0.0424 100k. 0.0237 0.0234 0.0234 0.0233 D. a a , - A ~ e t ~ y l i s o a m y l s u c c i n i c A c i d s . Dr. Lawrence kindly furnished us with specimens of the cis- and trcms-nal-methylisoamylsuccinic acids described in a recent communi- cation t o the Society (Proc., 1899, 15, 163) ; we obtained the following results for their dissociation constants. cis-Acid, m. p. 93". V. P V. m. 100k. 52.3 46-31 0,1323 0.0385 104.6 63.36 0.1810 0.0382 209-2 86-45 0.2470 0.0387 41864 114.98 0,3284 0.0385 K = 0.0385, trans-Acid, m. p. 141-142'. 9. PV. m. look. 183.4 65.61 0.1875 0.0236 366.8 87.69 0.2535 0.0234 733.6 11S.70 0,3393 0.0238 1467.2 154.7 0.4429 0.0240 K=0.0236.E. Tr ia I k y I-szc bs t i t ut ed Xu c cinic A cid s. Since we are now able to prepare ethyl PP-dimethylcyanosuccinate in large quantities, and as the introduction of a third alkyl radicle into this molecule is an easy matter, we have been able to investigateALKYL-SUBSTITUTED SUCCINIC ACIDS. PART III. 1305 R large number of trialkylsuccinic acids containing two methyl and a third variable radicle. Of these, we prepared the dimethylethyl-, dimethylpropyl-, dimethylisopropyl-, and the dimethylisoainyl-succinic acids, whilst Dr. Lawrence kindly gave us a specimen of dimethyl- isobutyl-succinic acid. The details of the preparation of these acids from ethyl PP-dimethyl- cyanosuccinnte are so similar t o those described under trimethyl- succinic acid in a previous paper (Trans., 1899, 75, 855), that me need not give them; the yields of trialkylated cyanosuccinic esters usually amounted to about 80 per cent.of those theoretically possible. Each oil was hydrolysed by boiling i t with excess of strong hydro- chloric acid in a reflux apparatus until the whole of i t had dissolved. The time required for the process varied with the mass and character of the third alkyl radicle introduced. Thus, whilst ethyl pp-di- methylcyanosuccinate required only 15 hours for complete hydrolysis with strong hydrochloric acid, the trimethyl ester required 40 hours, the dimethylethyl 48 hours, the dimethylpropyl 84 hours, the di- methylisopropyl 96 hours, and the dimethylisoamyl 144 hours under the same conditions.On cooling the liquid in each case, almost the whole of the acid separated as a white, crystalline powder which was afterwards purified by repeated recrystallisation either from strong hydrochloric acid or hot benzene. The only impurity likely to survive this treatment would be a small quantity of as-dimethylsuccinic acid resulting from any unchanged ethyl PP-dimethylcyanosuocinate in the oil hydrolysed; analyses of the acids and their silver salts, however, showed that in no case was it present.* On analysis : aa-Di~LethyLal-ethylsuccinic acid melted at 139 -1 40". 0.1826 gave 0.3684 CO, and 0.1349 H,O. 0,2109 of the silver salt gave on ignition 0.1169 Ag. C,H,,O,Ag, ,, Ag = 56.68 per cent. C = 55.0 ; H = 8.21. Ag=55.44. C,H,,O, requires C = 55.17 ; H = 8.05 per cent.Dissociation constaztt. 21. Pu. ?I&. 100k. 59.2 58.34 0.1667 0.0563 118.4 79.63 0.2275 0.0566 236.8 107.20 0.3063 0.0571 473.6 140.S 0.4023 0,0572 K= 0,0566. aa-DimethyZ-al-~~opyZsuccinic acid melted a t 145". On analysis : * as-Dimethylsuccinic acid, C,H,,O,, contains C = 49'31, H=6*81 per cent. and its silver salt contains Ag=60-00 per cent.1306 BONE AND SPRANKLING: RESEARCHES ON THE 0.2144 gave 0,4512 GO, and 0,1671 H,O. 0,2966 of the silver salt gave on ignition 0.1594 Ag. C,H,,O,Ag, ,, Ag=53.99 per cent. C = 57.40 ; H= 8.66. Ag = 53.72. C,H,,O, requires C = 57.46 ; H = 8.51 per cent. This acid also gave a liquid anhydride and an anilic acid melting at 166--'167'. Dissociation constant. V. PV. m. look. 108.5 78-68 0.2348 0*0601 217.0 105.40 0.301 1 0.0598 434.0 138-50 0.3956 0,0596 868.0 17650 0.5042 0.0591 K= 0.060.aa-Dimeth?/l-a,-isopop,yZsuccinic acid melted at 141 --I 42'. On 0.2072 gave 0,4355 CO, and 0.1620 H,O. 0.3172 of the silver salt gave 0.1680 Ag. analysis : C=57*31 ; H=8*69. Ag=53.69. C,Hl6O4 requires C = 57-46 ; H = 8.51 per cent. C,H,,O,Ag, ,, Ag = 53.99 per cent. The acid forms a liquid anhydride, and an anilk acid melting at 1 9 7 -1 9 9". Dissociation constant. V. P U S m. 100k. 66.1 35-66 0.1019 0.0159 132.2 46.96 0.1 342 0-0157 264.4 63.01 8.1SOO 0.0150 528.8 85-06 0.2430 0.0148 K = 0.0158. aa-Dirnethyl-a,-isobutylsuccinic Acid.-Specimen prepared by Dr. Law- rence. Melting point 143-1 44". Dissociation constant. 2'. P U * ?n. 100k. 273.0 101-4 0.2898 0.0434 546.0 123.3 0.3810 0.0429 1092.0 171.5 0.4900 0,0431 2184.0 223-9 0.6083 0.0432 K = 0.0432.aa-I)imethyl-a,-isoccinylsuccinic acid melted at 143 - 144". On analysis :ALKTL-SUBSTITUTED SUCCINIC ACIDS. PART III, 1307 0.2126 gave 0.4701 CO, and 0.17Sl H,O. 0.1926 of the silver salt gave on ignition 0.0965 Ag. C1,H,,O,Ag, ,, Ag=50*0 per cent. C = 60.31 ; H = 9.31. Ag = 50.1. C,lH,oO, requires C = 60.54 ; H = 9.17 per cent. Dissociation constant. 2.'. 121.2 242.4 484.8 969.6 P U S m. 83-43 0.2384 111.60 0.3189 145.50 0.4157 184.20 0.5263 K= 0,0616. 100k. 0.0616 0.0616 0.0610 0.0603 D i s c u s s i o n of R e s u l t s . The dissociation constants of a very large number of alkyl-substi- tuted succinic acids have now been determined ; in no other series of acids are the data available for a discussion of the connection between the chemical constitution and this characteristic physical constant so complete.On d, priori grounds, me should conclude that the value of the con- stant in this series would be largelyinfluenced by the following fac- tors : (1) The number of the substituting alkyl groups ; (2) their mass and ctiemical structure ; (3) the mutual influence of the two carboxyl groups, largely dependent on the distance between them. With regard to the third factor, it is obvious that the mutual effect of the two carboxyl groups in the molecule must increase the tendency t o ionisation in aqueous solution. As an extreme instance of this effect, we might quote the constant of malonic acid (0.163), which is ninety times as great as that of acetic acid (0*0018).The magnitude of this mutual reinforcement will vary inversely as the distance be- tween the two groups in question, and as there is good reason for believing that in the alkylsuccinic acids this distance decreases with the number of the substituting radicles, we must endeavour to distin- guish between the direct effect of successive substitutions and the accompanying indirect effect due to the approximation of the two carboxyl groups. It has been argued that because the direct observed effect of succes- sive methyl substitutions in the acetic acid series is to lower the value of the constant, it must necessarily be so in every other series, (compare Waiker, this vol., 397) but this contention is based on purely empirical evidence, and is unsupported by any ti priori con- sid eration.It remains now to see how far we can trace the effects of theseMonoethyl ............... 0.0085 Monopropyl ............... 0.00886 Monoisobutyl ............ 0.0088 Monoisoamyl ............ 0.0096 Trimethyl.. ................ 0.0320 Dimethylethyl ............ 0.0566 Dimethylisopropyl ...... 0.0150 Dimethylisobutyl ...... 0.0432ALKYL-SUBSTITUTED SUCCINIC ACIDS. PART III. 1309 Here, again, so long as the variable radicle remains normal an increase in its mass is accompanied by a marked increase in the constant, but this ‘mass’ influence is masked by the opposite effect of the ‘ is0 ’ structure iu the last three acids, and, again, the magnitude of this structural effect depends on the proximity of the ‘ is0 ’ linking to the carbon to which the carboxyl group is attached. We will now tabulate those symmetrically substituted dialkylsuc- chic acids whose constants have been determined.Trans. Cis. s-Dimethyl .............................. 0.01 96 0.01 23 s-Diethyl ............................... 0.0245 0.0201 s-Dipropyl .............................. 0.0250 0.049 s-Diisopropyl ........................... 0.0108 0.230 s-Diisobutyl .............................. 0 *02 2 6 0.056 Again, we find that so long as the two alkyl radicles have a normal structure, the value of the constant increases with their masses in both the cis- and trans-series. On the other hand, just as in the case of the aal-acids when the alkyl groups have an ‘ is0 ’ structure, we observe a ‘ lowering ’ effect in the trans-series and a ‘ raising ’ effect in the corresponding cis-series, these ‘ structural ’ effects being again most marked in the two diisopropyl acids.The conclusion may therefore be drawn that in this series of acids each alkyl group exerts its own influence upon the dissociation con- stant dependent upon its mass and structure. I n the case of normal radiclea, we have simply the effect of ‘ mass’ to consider, an in- crease in the mass of a variable radicle invariably raises the con- stant. The ‘structural’ effect in case of iso-radicles is opposed to that of mass, except in the case of cis-symmetrically substituted dialkyl acids, and its magnitude always depends on the proximity of the ‘ i s o ’ linking to the carbon atom to which the carboxyl group is attached. We have in our previous paper discussed the effects, direct or indirect, of successive alkyl substitutions on the constant of SUC- cinic acid. There can be no doubt as to the observed effects, for the constant of every monoalkylsuccinic acid is greater than that of succinic acid, those of the aal-dialkyl acids are all greater than the highest value observed in the case of the monoalkyl series, and those of the trialkyl acids we have studied are all greater than that of the as-dimethylsuccinic acid from which they are derived. Whether this general effect is direct or indirect is a matter of opinion, but if we consider it indirect, and due to the greater proximity of the two carb- oxyl groups, we have still further to explain why the constant of cis-s-di- isopropylsuccinic acid is so many times greater than that of any other VOL. LXXVII. 4 u1310 PERKIN AND HORSFALL : GENISTEIN. PART 11. cis-8-dialkyl acid, although there are no appreciable differences in their tendencies to anhydride formation. We have pleasure in stating that the greater part of the cost of the materials used in this investigation was defrayed by grants from the Research Fund of the Chemical Society. THE OWENS COLLEGE, M ANCH ESTE R.