OPTICALLY ACTIVE DIMETHOXYSUCCINIC ACID. 957 CII.-Optically Active Dirrzethoxysucciizic Acid and its De yivatives. By THOMAS PURDIE, F.R.S., and JAMES C. IRVINE, B.Sc. PREVIOUS papers on the use of silver oxide and alkyl iodide in alkyl- ating the esters of hydroxy-acids have shown that optically active mono- and di-alkyloxysuccinic and alkyloxypropionic acids can be readily obtained from active malic, tartaric, and lactic acids by this method. The alkyloxysuccinic acids mentioned are substances of considerable interest from a stereochemical point of view. Their close relationship to the common hydroxy-acids, which have formed the subject of so much research in this particular field, imparts of itself a special interest to them. Their etheric character protects them from the disturbing effects which the hydroxyl group is known to exercise on optical activity, and unlike most of the acyl derivatives of the hydroxy- acids, they can be examined as free acids or salts i n solution without risk of decomposition. They are endowed with much higher optical activity than the parent acids, and are therefore well adapted for the investigation of problems relating to this property.We have already described various representatives of this class of optically active compounds, but i t is evident that if general conclusions are to be reached on the points raised by their study, more extensive series of them must be examined. The present paper deals with dimethoxysuccinic acid, its methyl, ethyl, and prop91 esters, and some of its metallic salts.Jfetlql d-l)inLetl~o~~succiIaate. The observed rotation of the methyl tartrate used in the prepara. tion of this compound was + 2.82' in the superfused state ( I 3 1, t = 20'), the corresponding value recorded by A. Pictet being 2.84O. On adding the silver oxide (3 mols.) to the solution of the tartrate (1 mol.) in methyl iodide ( 6 mols.), a vigorous action ensued, which had to be moderated by cooling. After heating the mixture for some time on a water-bath, filtering, and distilling off the ether which was used in washing the silver iodide, a liquid was obtained which boiled nearly constantly at 132' under 12 mm. pressure and gave a distillate which crystallised quickly in radiating prisms. The substance, after being recrystallised from ether, melted a t 51°, and gave on analysis : I.C=46*70; H=7.12. 11. C = 4 6 * 5 5 ; H=6*98. C,H,,O, requires C = 46.60 ; H = 6.80 per cent,958 PURDIE AND IRVINE OPTICALLY ACTIVE The compound is readily soluble in water without undergoing per- ceptible hydrolysis, also in alcohol, benzene, or chloroform, and may be conveniently crystallised from carbon disulphide or ether. Unlike methyl tartrate, it cannot be kept superfused, and the rotation of the pure liquid had therefore to be taken at 60'. The result was a= + 93.48', I = 1.001, d 60°/4'= 1.1317, hence [U]T= + S2.52'. I n preparing ethyl diethoxysuccinate from ethyl tartrate (Zoc. cit.), the crude product contains a considerable quantity of a less active compound, which is removed with some difficulty. The reaction between methyl tartrate and methyl iodide, on the other hand, gives an almost quantitative yield of dimetboxysuccinate ; from 45 grams tartrate we obtained 46 grams of the recrystallised substance.The fact that three different preparations showed practically the same specific rotation, namely, + 104*66', 104*47O, and 104.60' in at 10 per cent. benzene solution at 20°, indicates that racemisation does not occur in the course of the chemical action, and this was further con- firmed by finding that fractional cry stallisation produced no appreciable change of activity. Ethyl d-Dimethoxysuccinate. I n preparing the alky loxypropionic esters containing two different alkyl groups (Trans., 1899, 75, 486), it was found that the hydroxyl of the ethereal lactates can be alkylated with silver oxide and alkyl iodide without any interchange with the carboxylic alkyl group occurring. We find that tartaric esters behave similarly, ethyl dimethoxysuccinate being produced by the action of methyl iodide and silver oxide on ethyl tartrate.The ethyl tartrate used in our preparations gave a= + 94110 (I= 1, t=20°), Pictet's value being 9.24'. The proportion of materials and the method of procedure were the same as described above ; the reaction here was apparently less vigorous, and a perceptible quantity of water was produced. From 41 grams of ethyl tartrate we obtained 45.5 grams of a thick, yellowish oil, which boiled at a cearly constant temperature, and gave the rotation a2O0== 95*96O (Z= 1). The methods used in the case of the methyl ester, for assuring ourselves t h a t the action was com- plete, not being available, the product was subjected to further treat- ment with silver oxide and methyl iodide.h second treatment with a third of the quantities of the reagents originally used raised the rotation to 98.66'; after a third similar treatment, the rotation found was 98-47', and after another distillation (b. p. 155' under 25 mm. pressure) 98.61'. The substance was accordingly regarded as pure. Analysis gave : C = 51.33 ; H = 7.82. C,,H,,O, requires C = 5P28 ; H= 7.69 per cent.DIMETHOXYSUCCINIC ACID AND ITS DERIVATIVES. 059 The compound was further identified by analysis of the dried barium salt obtained from it by hydrolysis wibh barium hydroxide, which gave Ba = 43.91, the calculated number for barium dimethoxy- succinate being 43.77, and by the fact that the acid prepared from this barium salt possessed the same activity as that prepared from methyl tartrate in the reaction already described.The ester did not solidify, and was much less soluble in water than the methyl homologue. Specific rotations taken in a 1 dcm. tube gave : d lOo/4'= 1,1055, [ a ] T = + 90*70°. CZ 15°/40=1*1020, [ a ] r = 90.26. d 20°/4'=1.0961, [.IF.= 8 9 - 9 6 . d 60°/40= 1.0556, [ a]F7 = 85.39 . Propyl d- Dinaeth oxgsuccinnte, We are indebted to Mr. E. J. Balfour, who is preparing some of the higher dialkyloxysuccinic esters, for the following data concerning this compound : +90*12O, Z = 1 , d 20°/40=1*0612, [u]$" = +84*92O. u t i O O - - + 82*98O, Z=1, d 60"/4'= 1,0237, [.I:"= + 81.06".d-Dimethoxysuccinic Acid. This acid was prepared from the methyl ester by hydrolysing it with a 10 per cent. aqueous solution of potassium hydroxide, acidifying, and extracting with ether, and also from the methyl and the ethyl esters by hydrolgsing with barium hydroxide and decomposing the crystallised hydrated barium salt with the calculated quantity of sulphuric acid. The latter is the preferable method, as ether does not extract the acid easily from an aqueous solution. The compound is readily soluble in water, alcohol, or acetone, much less so in ether, and is scarcely dissolved by benzene or carbon disulphide. It crystallises from water in small prisms and from acetone in largeplates. Crystals obtained from an aqueous solution, after drying in a vacuum, melted a t 151°, but not very sharply, owing perhaps to slight decomposition.Analysis of the acid, dried a t loo', gave C = 40.26 ; H = 5.77. C,H,,O, requires C = 40.45 ; H = 5.62 per cent. Observations on the rotatory power of the acid in solution are recorded below. The diacyl- and dialkgl-succinic acids in general yield anhydrides readily, and the dialkyloxysuccinic acids might be expected to behave similarly. Our attempts, however, to prepare dimethoxysuccinic960 PURDIE AND IRVINE : OPTICALLY ACTIVE anhydride were not successful. When the dry acid was treated with boiling acetyl chloride, and the excess of the reagent then evaporated, the residual liquid deposited well formed cubes, which melted a t a much lower temperature than the acid, namely, at about 77", and the substance still retained the low melting point after recrystallisation from chloro- form.On recrystallising, however, from boiling ether, needles were obtained which had approximately the same melting point as the acid. The melting point rose in a similar manner on heating the substance at loo", and on letting it stand for some days at the ordinary tem- perature in a vacuum. The low melting point might perhaps be due simply to solvent adhering to the acid, and the subsequent rise to its removal, but the observations suggest the possibility of isomeric change, and we intend to examine the reaction with larger quantities of material. An attempt to convert the acid into anhydride by dis- tilling in a vacuum resulted in complete decomposition.d- Dimethoxysuccinamide. When a concentrated solution of the methyl ester in methyl alcohol was saturated with ammonia, this compound was deposited slowly in the form of a mass of felted needles. After being dried at loo", it was analysed with the following results : I. C = 40.86 ; H = 7-22, 11. C = 40.84 ; H = 7.10 ; N = 16.09. C6H,,0,N, requires C = 40.91 ; H = 6.82 ; N = 15.91 per cent. The substance is insoluble in the ordinary organic solvents, and very sparingly soluble in cold water, but more soluble in boiling water, from which i t crystallises unchanged. As the following observations of its optical activity had consequently to be made on very dilute aqueous solutions, the results are only approximate. c = 0.72, I = 2, a2O0= + 1*36", hence [a]T= + 94.44".The amide was prepared*with the object of obtaining the imide from it by the action of heat, as an examination of this sub- stance, it was thought, would throw some light on the influence of ring formation on optical activity. The amide did not suffer any loss of weight when heated to 160" in an air-bath, but when heated strongly in a test-tube it fused and volatilised with a considerable evolution of ammonia and some charring. By distill- ation in a vacuum on a graphite bath, the substance entirely sublimed without fusion or charring in beautiful needles an inch long, which resembled the original substance in respect of insolubility and difficult fusibility, but showed a considerably higher specific rotation, namely, + 105.9'. A combustion giving -C = 40.80, H = 7-18 per cent.proved,DIMETHOXYSUCCINIC ACID AND ITS DERIVATIVES. 961 however, that the substance was unaltered amide, the high rotation being due probably to the presence of a small quantity of some more active product. Metallic d-Diinethoxysuccinates. The diammonium and ammonium hydrogen salts both crystallise readily, the former in needles, the latter in prisms. The dipotassium salt is very soluble, and was not obtained in definite crystals; the hydrogen potassium salt crystallises in radiating needles. The silver salt is very soluble in water and decomposes when its solution is evaporated, The magnesium salt on evaporating its solution leaves a gum, which solidifies to a glass. The following salts, whose rota- tory powers were observed, were analysed ; the numbers given are the percentages of metal in the dehydrated salt.Disodium Salt.-Feathery aggregates very : oluble in water. Found Na = 20.80 ; calculated 20.72 per cent. Sodium Hgdrgen Salt.-Minute prisms, less soluble than the normal salt, anhydrous at 100". Found, N a = 11.36 ; calculated, 11.50 per cent. Barium Salt.-Well developed, short prisms containing 5 mols. of water of crystallisation; sparingly soluble in water. Loss of water at, 168" ; H,O = 22.27 ; 5H,O requires 22-31. Found, Ba = 43*65,43*72 ; calculated, 43.84 per cent. One hundred C.C. of a n aqueous solution saturated at 20" contained 1.38 grams of anhydrous salt. Calcium SaZt.-Piisms, fairly soluble, containing 2 mols. of water of crystallisation, which are given off entirely only at about 160'.Loss of water; H,O=14*62, 14.22; 2H,O requires 14.28. Found, Ca = 18.55, 18.47 ; calculated, 18.52 per cent. Zinc XaZt.-Aggregates of prisms, containing 2 mols. of water of crystallisation, which are lost a t 160". Loss of water; H,O= 12.88; 2H,O requires 12-98. Found, Zn = 26.71, 27.03 ; calculated, 27.09. A solution saturated at 20" contains about 4.4 per cent. of anhydrous salt . The rotations of the acid and its metallic salts in solution are tabu- lated below. The observations were taken at 20" in a 2 dcm. tube, One or more solutions of each substance were prepared, and the others of different concentration were procured from these by dilution ; in the case of the acid and the sodium hydrogen salt, the quantities used were weighed, and the solutions made up to known volumes at 20°, but i n the case of the other salts, as they could not be dehydrated without a risk of impairing the activity, the concentrations were ascertained by weighing the dry residues left on evaporating known volumes, and controlling the result by estimat.ing the metal by in- cineration.The acid and salts were in general examined in solutions of nearly equivalent strength ; the approximate concentrations with962 PURDIE AND IRVJKE : OPTICALLY ACTIVE respect to anhydrous substance, in terms of a normal solution, are given in the column headed N. Rotatoi*y powers of solutions of d-dimethoxysuccinic acid and its salts. Substance. Acid.. .................... ) ) ....................... , , ....................... ,) ......................,, ....................... ,, ....................... 7 , ....................... Sodium hydrogen salt Disodium salt ........ Barium salt ........... Calcium salt ............ $ 9 3 , 3 , ? ¶ $ 9 7 9 Zinc salt ................. 9 , 9 9 9 9 Discussion of Results. C. 8.9091 3.5595 1.7797 17.5839 8'9104 4'4570 1 -781 2 10.0116 5.0078 2.0000 10 *1755 5.0830 2.0370 1.3775 10.6535 5-3160 2.1350 4-3690 2'1845 1 -0923 0.5461 + 89-29" 91.30 95.80 72.28 74 *74 75.39 76.63 57-03 57'31 58-50 52.68 53-02 54-00 27'22 43.83 46'37 - 5.95 +6'18 17-39 36.62 42-38 + 158'9'' 162.5 170.5 128.7 133.0 134.2 136.4 114'1 114'6 117'0 117.0 117.7 119'9 85'2 91'5 94.7 100.2 - 14.4 + 14'9 42 00 88'4 Ethereal Dirnethoxysuccinates. The ethereal tartrates, like the malates and lactates, exhibit a re- markable rise of optical activity when their alcoholic hydroxyl is slkylated.It seems probable that the alkylation with silver oxide and alkyl iodide is effected by simple substitution, possibly through the formation of an intermediate unstable silver derivative, and it is therefore very unlikely that any inversion of configuration occurs, such as Walden encountered in the interconversion of malic and chloro- succinic acids. As, however, in the opinion of its discoverer (Ber., 1899, 32, 1864), the change of configuration in this case occurs during the hydrolysis of the halogen-succinic acid by silver oxide, and as this re- agent was also used in our method of alkylation, we thought i t well to assure ourselves that no inversion bad taken place, by reconverting the dialkyloxysuccinic acid into tartaric acid.It will be seen in the succeeding paper that by the action of liydriodic acid on dimethoxy- succinic acid &-tartaric acid is produced. The ethereal tartrates and dialkyloxysuccinstes. of similar sign of rotation possess therefore a similar configuration, and the effect of alkylating the tartrates is to largely increase the dextro-rotation, This effect differs in a markedDIMETHOXYSUCCINIC ACID AND ITS DERIVATIVES. 963 degree from that produced by the introduction of acyl groups into the tartrates, which either alters the rotation in the positive sense com- paratively slightly, or more frequently produces an effect in the opposite direction, It is now generally recognised that the influence of substitution on the optical activity of a compound depends more on the chemical nature of the introduced group than on its mass, and that radicles of a like kind cause changes of rotation which are similar with respect to direction, and similar also, in a general sense, quantitatively. This point has been brought forward prominently in recent communications to this Journal by Frankland and his pupils (Trans., 1900, 77, 1108; 1901,79, 511), and by Guye (Trans., 1901, 79, 475).The following data selected chiefly from Frankland's paper (Zoc. cit.), to which we add our own observations on mono- and di-alkyloxysuccinates, will suffice to show the relative effects of the introduction of alkyl and acyl groups into ethyl tartrate and malate. To facilitate the comparison of the two series of compounds, we have halved the molecular rotations of the tartrate derivatives, and have regarded the malic compounds as derived from d-malic acid, the stereo-chemical analogue of d-tartaric acid.~~ ~ ~~ Malic derivatives. Ethyl monoethoxysuccin ate * ......................... Ethyl monome t hoxysuccin ate * ......................... Ethyl bromoacety lmalate.. Ethyl acetylmalate t ........ Ethyl malate t .............. Ethyl benzoylmalate.. ..... Ethyl p-toluylmalate ...... 17" 18 20 , 9 7 9 21 20 - t 121-0" 102.2 69 '9 52.4 20'2 11.4 0.68 Tartaric derivatives. Ethyl diethoxysuccinate : Ethyl dimethoxysuccinatc Ethyl diphenacetyltar- trate.. ....................... Ethyl dimonochloroacetyl~ tartrate ..................... Ethyl diacetyltartrate ......Ethyl tartrate ................ Ethyl dibenzoyltartrate ... Ethyl di-p- toluyl tartra te.. - to. + 122'1" 105.3 39'6 12.8 4.95 7 '93 - 123.6 - 242.2 * Trans., 1895, 67, 979. i- Zeit. physilld. Chena., 1895, 16, 495. $ Trans., 1899, 75, 159. rotation given is probably about 2" too low. A later preparation of this compound shows that the It will be seen that, with respect to their influence on the rotation of both malate and tartrate, the alkyl radicles stand a t the positive, the aromatic acyl groups a t the negative, end of the scale, whilst the fatty acyl groups, including phenacetyl, hold an intermediate position. The effects of the substitution of the hydroxylic hydrogen of the ethereal lactates by alkyl radicles (Trans., 1899, 75, 487), and by benzoyl and acetyl radicles (Proc., 1895, 11: 54), show a similar relation.964 PURDIE AND IRVINE : OPTICALLY ACTIVE Considering the members of the tartaric series as derived from the corresponding rualic compounds by the introduction of OR into the group CH,*CO,Et, it might be supposed that this substitution, occurring not in immediate proximity to the asymmetric carbon atom, would possibly not affect the rotation greatly.The supposition proves, in fact, to be correct with respect to the introduction of the alkyloxy- radicle into the monoalkyloxysuccinate, the dialkyloxysuccinates having, as will be seen, approximately the same rotation as the monoalkyloxysuccinates. The introduction of hydroxyl, on the other hand, into ethyl malate, or of an acyloxy-group into the corresponding acylmalate, produces a marked effect, which shows itself in the rota- tions of the tartrate and its derivatives by a gener.al shifting of the values in the laevo-direction.That is to say, the rotation of the mono- alkyloxysuccinate is scarcely affected by the introduction of a second alkyloxy-group ; the dextro-rotation of the malate is considerably reduced by the introduction of another hydroxyl group, whilst with the acylmalates the effect of the substitution is still greater in the same direction, the slight dextro-rotation, for instance, of the p-toluyl- malate becoming a powerful laevo-rotation in the di-p-toluyltartrate. It is impossible a t present to offer any explanation of this difference in the behaviour of the monoalkyloxysuccinates and acylmalates with respect t o the effect of further substitution ; it may be due either to the difference in the nature of the introduced groups or to the different states of dissymmetry of the parent monosubstituted compounds, or to both causes combined.I n view of recent researches, and more particularly of Frankland’s exhaustive survey of the known homologous series of optically active compounds, which exhibit a maximum rotation (Trans., 1899,75,347), it must be admitted that the attempt to find a relation between Guye’s product of asymmetry and the rotatory powers of compounds has not met with success, and will probably have to be abandoned. Although failure has attended this attempt, the more general form of the original conception put forward by Guye and Crum Brown still survives, and may serve as a guide in research.According to this conception, the measure of rotatory power may still be represented as the product of the differences of each pair of four coefficients, the values of which, however, are conditioned by other factors besides mass, and a pro- gressive variation in the value of one of these may result in the occur- rence of maxima of rotation. Homologous series, therefore, in which the phenomenon of a maximum rotation is found, still deserve particular attention. It will be seen, from our abservations tabulated below, that the specific rotations of the three dimethoxysuccinic esters at 60° show a diatinct maximum at the ethyl term.DIMETHOXYSUCCINIC ACID AND ITS DERIVATIVES. 965 [a]?. [1f]r.[a]:'*- Methyl.. ............ - - 82'5 Ethyl ............... 90.0 210% 85.4 Propyl ............. 84.9 222'4 81.1 hfol. vol. Mol. vol. [MI:'. calculated experi- for 15". mental. 170.0 151'5" 182.0 (60") 199.8 213.7 212.3 (15") 212.5 245.9 2 4 6 9 (20") It mas impossible to take observations on the methyl ester at lower temperatures, but even if the rise of rotation attending the fall of temperature from 60° to 20° were greater for this compound than for the other two, which might be the case, the maximum rotation exhibited by the ethyl term would probably still persist a t 20°, Frankland (Zoc. cit.) concludes, from certain considerations, alluded to below, that the maxima of specific rotation exhibited by the ethereal malates and lactates are probably attributable t o the depression of the rotations of the lower members of the series by molecular association.The maximum exhibited by the dimethoxysuccinates cannot, however, be accounted for in this way. The methyl ester, it is true, according t o Traube's method of caiculating association factors, should be con- siderably associated a t ZOO, as its experimental molecular volume, even at 60' (see the Table), is only just in excess of the value calculated from his constants, which refer to 15', and the ethyl term is little, if a t all, associated a t the lower temperature. It is shown, however, in the succeeding paper (p. 973), that the specific rotation of the methyl ester at 20' in water is 7S.5', and that the substance under these con- ditions has a normal molecular weight ; that is to say, the dissociating solvent, water, lowers the rotation to a value even below that of the pure liquid a t 60°, whilst the rotation of the ethyl compound, i t was found, is little affected by water.Assuming, then, in accordance with prevalent ideas, t h a t associated molecules are present in the pure liquid methyl ester, and that they influence the rotation, their effect would be to raise it, and, consequently, were the methyl compound in the unimolecular condition, the maximum exhibited by the ethyl term would be still more pronounced. The molecular rotations, it will be seen, increase from the methyl term upwards but tend towards a maximum. The completed series would probably present the same phenomena as others in which a maximum occurs, of which Guye and Chavanne's amyl esters of the fatty acids (Bull.Xoc. China., [iii], 1896, 15, 183, 275), Reitter's ethyl acetylmalates (Zeit. phpsikal. Chew., 1901, 36, 164), and Frankland's VOL. LXXIX. 3 u966 PURDIE AND IRVINE : OPTICALLY ACTIVE glycerates and diacetylglycerates (Trans., 1894, 65, 755) are typical, namely, a rise of molecular association to a maximum, which either remains nearly constant or is followed by a more gradual fall. Frankland, in the paper already quoted, suggests that the phenomenon of maximum specific rotation exhibited by certain homologous series is probably attributable to two distinct causes; in the case of the ethereal malates and lactates, the maximum is only apparent, being reasonably explicable as due to the association of the initial terms; in that of the tartrates, glycerates and diacetylglycerates, the maximum cannot be thus accounted for, and is due to some other cause.He is led to this conclusion by the observation that, whilst ethyl malate has a higher specific rotation than methyl malate, the order of the values for the corresponding benzoyl- and toluyl-malates is reversed, this phenomenon being coincident with the fact that the malates, on the evidence of Traube’s method, are associated (the methyl term, however, much more so than the ethyl term) and the acylmalates, referred to, un- associated. He finds similar relations on comparing the malates with Walden’s fatty acylmalates and chlorosuccinates, and concludes that it is not improbable that the real values of [aID for the unimolecular malates diminish in passing up the series from the methyl term.A similar argument and conclusion apply to the lactates. On the other hand, the maximum rotation observable in the tartrates, glycerates, and diacetylglycerates cannot, he thinks, be thus explained, because it is so very pronounced, and because in their substitution compounds, which show little or no evidence of association, the relationship between the rotations of the methyl and ethyl esters is retained. We doubt if the facts really warrant this explanation of the maxima of rotation presented by the malates and lactates. First, with respect to the reversed order of the specific rotations of the initial terms of the series of substituted malates, the reversal in question is not quite general.The decrease of values on ascending the series of fatty acylmalates is so slight and irregular as to be within the limit of experimental error, and the case of the chlorosuc- cinates cannot be cited in support of the hypothesis, if Walden’s views, (Ber., 1899, 32, 1864) published since Frankland’s paper, are correct. In Walden’s opinion, the dextrorota tory chlorosuccinates correspond in configuration to theZ-malates, and ought, therefore, according to the hypo- thesis, to show an increase of rotation with ascent of the series instead of a pronounced decrease which they actually exhibit. Further, we doubt if the assumption on which the hypothesis is based is warranted. It is assumed, namely, that when a series of esters is transformed by sub- stitution into a new aeries, if the supposed disturbing influence of association is absent, the members of the substituted series will present the same order of rotation values as the parent series, each rotationDIMETHOXYSUCCINIC ACID AND ITS DERIVATIVES.967 being simply shifted by a certain amount in the positive or negative direction, as the case may be. This may not, however, hold true, for independently of any effect due to changed degree of association, the substitution may influence the state of dissymmetry of successive members of the series in different degrees and so produce a considerable change in the relation of their rotation values, or even reverse their order from the first term onwards. The dimethoxysuccinates present a case in point. By methylating the tartrates, the maximum specific rotation of the series is displaced from the propyl to the ethyl term, with the result that, although none of the compounds concerned are, according to Traube’s method, affected by association, ethyl dimethoxy- succinate has nevertheless a higher specific rotation than the propyl compound, whilst, of the corresponding tartrates, the prop91 compound has the higher rotation.I n default of more conclusive evidence, we incline t o the view that, although the rotations of the initial terms of the series of malates and lactates may probably be lowered to some extent by molecular associa- tion, the maxima of rotation exhibited by them is attributable to the same causes as those of the tartrates and other series, The discussion of this subject raises the fundamental questions of the influence of molecular association on rotation and of the trust- worthiness of Traube’s method of determining the association factor.In the succeeding paper, it is shown that solvents may’produce marked changes of rotation without any change of association, and that association may be similarly produced without change of rotation ; association evidently does not play a predominant part in the changes of rotation due to solvents, and it is extremelydoubtful if it has much influence in the case of pure liquids. Traube’s method of determining the association factor has not met with general acceptance, and it is doubtful how far its results may be relied on. The association factors of the lower members of a homologous series of esters deter- mined i n this manner are frequently greater than unity, and diminish gradually, on ascending the series, to the latter value; this is inter- preted in discussions on optical activity as indicating gradually decreasing molecular association, but it is commonly ignored that on ascending further i n the series the value of the factor does not remain constant, but continues to decrease steadily, and yet the latter phenomenon is surely equally significant with the former.This decrease can scarcely be held to indicate dissociation, and the more obvious conclusion seems to be that on ascending the series there is a gradual increase of molecular volume in excess of that due to the in- crease of mass, caused, it may be supposed, by a lessening of the internal forces of the liquid.The molecular expansion which accompanies the passage upwards through the lower members of a 3 u 2968 PURDIE AND IRVINE : OPTICALLY ACTIVE series, such as the esters of the hydroxy-acids, is due, no doubt, partly to disgregation of associated molecules, but the expansion evidently does not cease at the term where association is supposed to disappear, but extends indefinitely through the series. This suggests a doubt whether in such series Traube's method can be relied on for ascertain- ing even roughly the degree of association or the point in the series where association ends. T. 8. Patterson's views on the cause of the changes of rotation produced by solution (Trans,, 1901, 79, 167, 477) suggest the ides that the changes of rotation attending the ascent of a homologous series of homogeneous liquids may also be due largely to the lessening of the internal forces, manifested in the abnormal increase of mole- cular volume above referred to.Xolutions of Dimethoxysuccinic Acid and its Xults. The rotation of dimethoxysuccinic acid in aqueous solution is more constant, as was to be expected, than that of tartaric acid; it in- creases with dilution, like ihat of the hydroxy-acid, but the relative increase is much less. Dimethoxysuccinic acid, however, does not exhibit quite such a constant rotation as the monomethoxy-acid (Trans., 1895, 67, 949), and the two acids do not show the quan- titative relation presented by their ethyl esters (p. 969), half the molecular rotation of the former (68.2') being much in excess of that of the latter acid (48.9O).The ion of the former acid, as pointed out below, is also more active than that of the latter. It is worthy of notice that in acetone solutions, on the other hand, in which the rotations of both acids are much raised, the relation in question holds good, the mole- cular rotation of the monomethoxy-acid ( 8 8 9 , Zoc. cit.) approximating to half that of the dimethoxy-acid (85.2'). With respect to the salts, in dilute solution they are dextrorotatory like the acid and its esters, and their rotations increase with dilution. The calcium salt shows a much greater rise with dilution than the normal sodium salt, and the molecular rotations of both barium and calcium salts in dilute solution fall further short of the maximum mole- cular rotation of the sodium salt than the law of Oudemans and Landolt would lead us to expect.The monoalkyloxysuccinates show similar relations (Trans., 1893, 63, 239). According to van 't Hoff this behaviour of the salts of bivalent metals of polybasic acids is probably attributable to the influence of ring formation, as well as to less advanced electrolytic dissociation. This view is supported by the fact that the molecular rotations of the corresponding salts of the monobasic alkyloxypropionic acids (Trans., f899,75. 490), approximate much more closely to the maximum. On the other hand, the remark-DIMETHOXYSUCCINIC ACID AND ITS DERIVATIVES. 969 Normal alkali salt. able behaviour of zinc dimethoxysuccinnato, which even in a 4 per cent.solution is already lavorotatory, is not to be accounted for as van' t Hoff suggests, as the zinc alkyloxypropionates (Zoc. cit.) show a simi- lar abnormally rapid change of rotation with change of concentra- tion. The known low degree of electrolytic dissociation of zinc salts (Zeit. physikal. Chern., 1898, 27, 399), and hydrolytic dissociation are probably the disturbing factors hero. The rotations of aqueous solutions of the mono- and di-alkyloxy- succinic acids and their salts show some further relations which de- serve notice ; these may be seen from the following data abstracted from the present and previous papers (Trans., 1893, 63, 239 ; 1895, 67, 965 ; 1899, 75, 159). The numbers quoted are molecular rota- tions, halved in the case of the dialkyloxysuccinic compounds, and the differences given are the percentage rises of rotation between successive terms in ascending the series.Diff' Mono- and di-alhJoxysuccinnic acids. Monometboxysnccinic .. , Monoethoxysuccinic .. . , . . Monopropyloxysuccinic.. . Dimethoxysuccinic.. . . . . . . . Diethoxysuccinic . , . . , . . . . Acid. 48.9" 52 *7 63 -8 68 -2 68 -5 I- Diff. 7.8" 21.0 Hydrogen alkali salt. 43 '6" 57 .a 69'2 58'5 - - Diff. 32-6" 19-7 - I-- 21.4" 35-9 43-5 59.9 51'4 6723" 21 *2 The ethereal monoalkyloxysuccinates (Trans., 1895,6'7,979) exhibit a rise of molecular rotation in passing from the methoxy- to the corre- sponding ethoxy-compounds ; the esters of the propyloxy-acid have not yet been prepared, but it is probable that the increase will still con- tinue to this term of the series.I n agreement with the esters, the monoalkyloxy-acids, acid salts, and normal salts, as will be seen from the table, show also a rise of molecular rotation on ascending the series. The rise between the ethoxy- and propyloxy-compounds is uniform, namely, 20-21 per cent, whether acids, acid salts, or normal salts are considered, but the relations of the methoxy- to the ethoxy- compounds are quite different, the rise here being much less for the acids (7.8), much greater for the acid salts (32.6), and still greater for the normal salts (67.8). The effect of the methoxy-group, ascompared with that of the higher alkyloxy-radicles, is to raise the rotation of the slightly dissociated acid and to lower the rotation of its ion.This effect of the lowest term of this series of radicles in raising tho rota-970 OPTICALLY ACTIVE DIMETHOXYSUCCINIC ACID. tion of the acid in aqueous solution is of some interest, as it explains similar perplexing relations encountered in the alkyloxypropionates (Trans., 1899, 75, 490; 1898, 73, 874). The following diagram represents the relations of the alkyloxypropionic compounds with respect to the values of their molecular rotations, so far as they have been studied : Methoxy-ion < ethoxy-ion < propyloxy -ion Methoxy-acid > ethoxy-acid (liquid). Methoxy-esters > ethoxy-esters ( ,, ) The difference found between the rotations of the methoxy- and ethoxy-acids in the liquid state was very slight, but in general it may be said that in the case of the undissociated esters and slightly dis- sociated acids, particularly in the presence of water, the methoxyl group has a peculiar effect in raising the optical activity.With respect to the dialkyloxysuccinic compounds, the methoxy- esters are less active than the ethoxy-esters, so far as these have been examined, and it might have been expected that aqueous solutions of the two acids would show the same relation, but here again the pecu- liar effect of the methoxyl group asserts itself, with the result that the acids have nearly the same molecular rotation ; in contradistinction to what might have been expected from the relations of the monoalkyl- oxysuccinic acids, which have been indicated above, the effect of the methoxyl group in raising the rotation extends to the ion of di- methoxysuccinic acid, sodium dimethoxysuccinate having a higher molecular rot ation than the corresponding diet hox y-sal t. In conclusion, we point out a general relation which seems to hold between the hydroxy-acids and the corresponding alkyloxy-acids, which has been alluded to in previous papers (Trans., 1899, 75, 160), and finds further illustration in tartaric and dimethoxysuccinic acids. The molecular rotations of dilute aqueous solutions of the normal d-malates, d-lactates, and d-tartates are much higher in the dextro- sense than those of the corresponding free acids ; in the case of the alkylated derivatives, on the other hand, the rotations of the normal alkali salts are much lower, or, at most, only slightly higher, than those of the free acids; that is to say, the rise of rotation produced by alkyl- ntion tells much more strongly on the hydroxy-acids than on their salts. The known marked influence of hydroxyl groups on the physical properties of compounds, and the great effect of varying concentration on the rotation of aqueous solutions of the hydroxy-acids, suggests that the cause of the general relation just indicated is to be sought for in some peculiarity of the latter acids, which has the effect of lowering their optical activity. We are a t present engaged in an investigation of the higher members (aqueous solution). Methoxy-acid > ethoxya-cid < propyloxy-acid ( ,9 1INFLUENCE OF SOLVENTS ON ROTATORY POWER. 971 of the series of dial kyloxysuccinic acids and their derivatives, which we hope may throw some light on the relations of the members of the group with respect to optical activity. UNITED COLLEGE OF ST. SALVATOR AND ST. LEONARD, UNIVERSITY OF ST. ANDREWS.