THE OPTICAL ROTATIOK OF MALIC ACID* BY WILDER D. BANCROFT AND H E R B E R T L. D b V I S
Malic acid is regarded as one of the most satisfactory substances to be used in the study of optical activity, and probably only tartaric acid, because of its greater availability, exceeds malic acid in the number of times it has been made the subject of such investigations. The single asymmetric carbon atom of malic acid intrigues with its simplicity and yet' the very large amount of work that has been done on this innocent-appearing substance reveals nearly all the optical idiosyncrasies that can be exhibited by the most complex compound. Under the proper conditions the optical rotation of malic acid changes not only in magnitude but even in sign with change in-its concentration in various solvents, change in the wave-length of light employed, changes in the temperature, and other changes in its environment such as change in solvent or the addition of foreign substances to its solutions. Such marked changes are not peculiar to malic acid but are certainly not t o be T.4BLE C
63.2 45.68 36 .oo 26. j3 20.92
.8; 10.65 Ij
7.52
hLlalic * h i d 11
1
Sodium Malate (a)D
C
M
(a;D
788" 4-0.600
4.93 4.71
+,?.azo t. 3 . 3 . ; 4-2.3; +o 68
4.71 3.41
+I.
8;.76
2.68 1.99 1.56 I .18 0.79 0.j6
+0.003
83.94 76.08 65.54
-0.589 ,050
ji,I4
-I .228
46.78 36,5I 16.56
-1
-2.346 -2.479
4.27
3.68 3.21 2 .62
-0. j 8
- 2 ,
j4
.oj
-4.24
0.93
-6.94
2
expected from a general study of optical activity. I n this paper an explanation of these abnormalities is proposed in terms of malic acid and in such a manner that it' may be extended t,o the discussion of analogous compounds, chief among which is tartaric acid. Of these abnormalities the one most readily studied is the change in rotatory power with dilution of the solutions. It appears to be no mere coincidence that those substances which show marked abnormalities in this property exhibit abnormalities also in other changes of environment and the conclusion seems justified that one explanation may suffice for all these changes of the optical rotatory power under the various conditions. Sumerous investigations have shown the existence and character of the rotation-dilution change of malic acid. One which agrees well with later * This work is part of the programme n o w being carried out a t Cornell University under a grant from the Heckscher Foundation for the Advancement of Research established by August Heckscher at Cornell University.
898
WILDER D. BASCROFT A S D HERBERT L. DAVIS
results, including our own, was that of 1Voringer.l His data for the change in the rotatory power of malic acid with change of concentration is given in comparison with the same data for sodium malate according to Thornsen2 in Table I. I n this table, as elsewhere in this paper, c refers to the number of grams of solute in 100 cc of solution, 31 is the number of mols of solute in 1000 cc of solution, and (a)n is the specific rotation calculated from the relation a, x v (a)D = 1 x c where aD is the observed rotation of the plane of sodium light, 1 is the length of the tube in decimeters, and c is the number of grams of solute contained in the volume u of the solution. Table I shows that ordinary I-malic acid is levorotatory in dilute aqueous solution, its specific rotation decreases with increase in concentration, becoming zero for the D light a t about 34Yc acid; more concentrated solutions are dextrorotatory. The rotation of the sodium salt changes similarly,showing however, both in the dilute and in the concentrated solutions a higher numerical value for the rotation. Various experiments were made by the present authors to verify and extend the existing data for malic acid. The acid used was I-malic acid purchased from the Eastman Kodak Co. and used without further purification. In the presence of potassium hydroxide and uranyl nitrate it showed a specific rotation of -470' under the same conditions as those for which Ralden reported - 465'. Later another sample in the presence of ammonium hydroxide and uranyl nitrate gave -418' as compared with -436' found by Holmberg. There was a small amount of impurity, apparently calcium malate, insoluble in alcohol and in acetone. Several titrations with alkali indicated a purity of about 99.8%. I t melted sharply a t g g O - ~ o o O . To check the data from the previous authors for the rotation-dilution phenomenon, some of the I-malic acid was made up by weight to a concentrated solution and diluted in stages. The rotations were read in a Franz Schmidt and Haensch polarimeter reading t o O.OI', the solution being contained in a 0.947 decimeter tube at room temperature, which was usually The source of illumination was sodium light from a sodium from 2 jo to 30'. carbonate bead on a flat coil of platinum wire in the flame of a Fisher burner. The data for the dilution-rotation run on l-malic acid are; Concentration = 63 . o o Ij.jj 7.87 3 1 . jo aD 0.61' - 0,170 - 0.29' -0.16' - I .94O -2.140 - 0.57O (a)D I . 0 2 O Later in the investigation, when it was thought that the dextrorotation of malic acid might possibly be due to the formation of d-malic acid in the solution, some d-malic acid was prepared by the method of H ~ l m b e r g by ,~
+ +
'2. physik. Chem., 36, 336 (1901). 143, 753 (1887). Ber., 60, a z o j ( 1 9 2 7 ) .
* J. prakt. Chem.,
THE OPTICAL ROTATION OF MALIC ACID
899
hydrolyzing sodium l-chlorosuccinate by small additions of sodium hydroxide so that the solution was always alkaline. The acid was precipitated as the lead salt and freed by hydrogen sulphide. A rotation-dilution run on this acid gave the following data; Concentration = aD ( 4 D
-
42.96 0.16' 0.39'
PI
.48
+ 0.19' + 0.93'
5.37
0.74 + 10.18"
+O.IO"
f 1.77'
+1.96'
The concentration of these solutions was determined by titration with alkali, which seems the preferable method. These data indicate that both forms of malic acid are affected by the dilution changes, passing through a concentration of inactivity and exhibiting in concentrated solutions rotations opposite in sign to those shown in dilute solutions. The salts behave similarly. -4s shown in the data for l-malic acid, the dextrorotation continues to increase with concentration, extrapolating t o about +5.8' for the pure anhydrous acid. Walden fused some Lmalic acid and supercooled it to 17', finding its specific rotation + 5 . z o , in fair agreement with the extrapolated value. Solubility limits the study of tartaric acid somewhat but the dilute solutions are dextrorotatory, concentrated solutions (supersaturated) are levorotatory, and Biot found that fused plates of d-tartaric acid are levorotatory, in complete agreement with the facts for I-malic acid. In contemplation of such data Landolt said;' "Such phenomena may perhaps be explained by the assumption that when between the molecules of an active substance (turpentine) other molecules (alcohol) are interspersed, there results a certain modification of the former in such a way that in every molecule the relative separation of the atoms, their arrangement in space, as well as the kind of atomic movement is somewhat altered. This effect will be more marked the greater the number of inactive particles." The purpose of this paper is to suggest an explanation of this and similar changes in the rotatory power of malic acid. This explanation is that levomalic acid may exist in two tautomeric forms having these formulas, if one wishes to retain normal valences: Form I (Levo-)
Form I1 (Dextro-)
Ho\
Ho\
o=c 1
HO-C
/I
0
HOCH
1
\ i CH
1
HCH
i
COOH
HCH I
COOH "Das optische Drehungverrnogen,"
210
(1898).
900
WILDER D. BANCROFT AND HERBERT L. DAVIS
For reasons to be elaborated later, form I is considered levo-rotatory and form I1 dextrorotatory, the two forms having different rotatory dispersions. Form I is the dilute solution form while form I1 will predominate in concentrated solutions. We realize that this is by no means a new suggestion. As long ago as 1858 Arndtsen suggested for tartaric acid: “If one should imagine two active substances which do not act chemically on one another, of which one turns the plane of polarization to the right, the other to the left, and, in addition, that the rotation of the first increased (with the refrangibility of the light) more readily than that of the other, it is clear that on mixing these substances in certain proportions, one would have combinations similar to those of tartaric acid.” Since the structure and properties of tartaric acid are quite comparable to those of malic acid, any considerations applying to the one should apply a t least qualitatively to the other. I n a number of papers R. de Malleman’ has shown the properties of tartaric acid to be similar to those of malic acid and similarly affected by certain changes and has interpreted his results on the assumption that the variations observed are due to the presence’in solution of two unlike compounds with inverse rotatory powers. Longchambon* has come to a similar conclusion. “Solutions of tartaric acid behave as if they contained two active components, the one dextrorotatory, the other levorotatory and of different dispersive powers; one may suppose in general that the dextrorotatory substance is ordinary tartaric acid, the levorotatory substance may be an isomer, a polymer, an anhydride, an internal ester, etc.” He deduces the properties of these two forms from the properties of the tartaric acid. Among others Astbury and Lowry have contributed to this problem. On the basis of crystallographical measurements, Astbury3 discussed the crystal structure of tartaric acid. He concluded that the four carbon atoms in the tartaric acid molecule in the crystal are in an irregular spiral formation, as are also the four hydroxyl groups although in an opposite sense. The dextrorotatory power of ordinary tartaric acid is associated with the carbon nucleus spiral which alone under all conditions of solution, dilution, hydration, etc. possesses a stability. Such influences as solution, ionization, and solvation would tend to destroy the levorotatory action of the hydroxyl spiral. Lowry4 replies to this that Astbury’s explanation cannot be valid for there is no known relation between the degree of polymerization and the rotatory power of an optically active acid. Astbury’s idea of the persistence of the hydroxyl linkage between molecules of the acid even in dilute solution is of the nature of polymerization and should show as such. Yo data for this can be found. Further Lowry shows that the rotatory power of ethyl tartrate cannot be correlated with its degree of polymerization in the various solvents emlCompt. rend., 173, 474 ( 1 9 2 1 ) . Compt. rend., 178, 951 (1924). 3 Proc. Roy. SOC.,lOZA, 506 (1923). Lowry and Cutter: J. Chem. SOC., 125, 1 4 6 j (1924).
THE OPTICAL ROTATION O F 31.4LIC ACID
901
ployed. This does not meet Astbury on his own ground but will probably satisfy most people. Lowry and Cutter say: “In our opinion the explanation of this phenomenon is to be sought in some intramolecular change of structure or configuration rather than in the intermolecular action between contiguous molecules.” Lowry and Burgess’ had suggested that the hydroxylic hydrogens of tartaric acid and its esters may be coordinated internally with the carbonyl groups as in the formula below, where the hydrogens in question are shown as bivalent. The corresponding co-ordinated formula for malic acid is also given. HOC-0 HOC-0
I : H I : HC-0 I
I :
0-CH
H
:
:
j
HzC
H HC-0
:
I
HOC = 0 Malic Acid
0-COH Tartaric Acid
Lowry has certain lines of evidence which he believes indicate the existence of such hydrogen linkage. Most chemists, however, are not yet ready to admit the possibility of the existence of bivalent hydrogen. Since there is no known way of differentiating between the formula proposed by Lowry and the one here offered, this point may well be left open. Somewhat earlier than those just mentioned was the suggestion of hrmstrong and Walker which is quite similar to this one now made. Clough2 discusses their suggestion in these terms * “Armstrong and Walker suggest four possible formulas for the isodynamic forms of tartaric acid: COOH
COH
I 0/ \CHOH I I1 I CHOH 0 CHOH I \ / CHOH
COOH
I
I:>
I 51 0 . j 31
6.0851 -14.34'
-18.77'
-20.17'
-zo.~o'
0.25
51
-21.54'
Probably no one would claim any ionization for ethyl malate in alcohol and yet these data show that the rotation-dilution change is closely analogous to that of malic acid in water. Again the concentrated solutions lie nearly on a straight line and the most dilute solution exhibits a greater levorotation than the linear relation provides. Other solvents similarly increase the optical rotatory power of ethyl malate. A half-molar solut,ion of the ester in benzene showed, (M)D = - 15.63', and in acetone (M)D = - 24.72'. Further evidence for the inadequacy of the ionization theory here will be found in a study of the effect of added electrolytes on solutions of malic acid and the malates. If a strong acid such as HC1 be added to a weak acid such as malic acid, the first effect will be to repress the ionization of the weak acid. That this is true in the case of malic acid will be shown in the table below where are given the specific rotations of malic acid in various concentrations in the presence of varying amounts of hydrochloric acid.
Effect of HC1 on 1-Malic Acid in Aqueous Solution Malic acid conc 0 2 j M 0 j 51 SI I n water only -3 15' -2 36' --I 65' I n 0 . I Y HC1 -2 20 -I 89' -I 6;" o jXHC1 --I 5:' I oXHC1 -I 26' j N HC1 f z 10' +Z 52' + 3 IO' IOX HCl + 5 67' + 5 98' + 6 93'
2
XI
-0
86"
-0
83'
+ 4 65' (+; 15")
These solutions were prepared by weighing the required amount of 1-malic acid, adding the calulated amount of strong HC1 and diluting t'o the required volume. Thus the solution (a)D = - 1.89' was half molar with respect to malic acid and tenth normal with respect to hydrochloric acid, and gave a reading of aD = - 0 . 1 2 ~ in a 0.94; dm tube. The most stronglydextrorotatory value is extrapolated from a solution 8N with HCl. There are obviously two effects here tending in the same direction. The first is an ordinary repression of the ionization of the malic acid, producing the dextrorotatory form of the molecular acid, and shown in the dilute solutions on addition of small amounts of hydrochloric acid. The ionization constant of malic acid is given as 1 x 1o-I which means that the o.5hI solution will be between I and 2% ionized. For solutions more concentrated than this, the O . I XHC1 has no effect since there is practically no dissociation
WILDER D. BANCROFT AND HERBERT L. DAVIS
916
to be repressed and the acid is not strong enough to have any marked effect on the second change. This second change is the effect of the strong mineral acid to favor the formation of the undissociated dextrorotatory form of malic acid. A little of the mineral acid represses the ionization to the dextro form; a large amount of acid displaces the equilibrium far in favor of the dextro form. This is the effect early reported by Schneiderl who observed that this effect was about ten-fold greater when sulphuric acid was used than when acetic acid was added. The ionization theory is quite inadequate t o explain such large effects. I t may be added that strong sodium hydroxide solutions likewise have a dextrorotatory effect on sodium malate. It is well known that boiling malic acid in the presence of strong acid or alkali dehydrates it to fumaric acid, COOHCH:CHCOOH, but this would result only in a loss of activity and not in a gain of opposite rotation. This effect of hydrochloric acid is not restricted to aqueous solutions but is found also in alcoholic solutions. Thus o.gM solutions of malic acid with increasing amounts of acid showed the following rotations in absolute alcohol.
Effect of HC1 on 0.5 M Malic Acid in Alcohol Normality of HCl I I .8 4 -11 .8z0 -6.46' (&ID - 12.76' -15.85' -8.66" (MID - 1 7 . IO'
7N -0.790 -1.050
The effect of concentration of the malic acid is not so marked, as will be seen in the following solutions which are all I .8Kwith respect to hydrochloric acid.
Effect of Concn. of Malic Acid in 1.8 N HC1 Alcoholic Solutions Concentration of malic acid 0.25M o.5M M (a)D
-12.6"
-11.82~
(M)D
- 16.89'
-15.85'
-10.87' - 14.67'
I n all probability there was some esterification in these solutions but they were all run promptly after being made so that the effect is negligible. They demonstrate that, although alcohol favors the levorotatory form, in alcohol, as in water increasing concentration of malic acid shifts the equilibrium in favor of the dextrorotatory form and that increasing concentrations of hydrogen chloride have the same effect. The levorotatory effect of the alcohol makes it more difficult there to get dextrorotatory solutions but in one case 9 N HC1 caused 0.25 M malic acid in alcohol to show a rotation (M)D = +5.06' which is about 3' lower than a similar aqueous solution would have given. The second effect is the only one to be considered if one uses ethyl malate in alcohol containing increasing amounts of hydrogen chloride.
Effect of HC1 on 0.5 M Diethyl Malate in Alcohol 0 Ii Concentration of HCI ( W D
Ann., 207, 257 (1881).
-zo.7o0
-18.38'
4 N -g.50°
THE OPTICAL ROTATION OF MALIC ACID
917
The hydrogen chloride can not be repressing ionization for there is none. The effect of HC1 on diethyl malate in alcohol is of the same nature as that on malic acid in aqueous solution. I n both solvents addition of HC1 favors the formation of the dextrorotatory, ethylene oxide, form. As hydrogen chloride affects profoundly the structure and rotation of malic acid in solution, so also do various salts affect the malates. This will be shown by the data on the following solutions made by weighing out 0.879 g. I-malic acid, neutralizing this with NaOH and adding the calculated amounts of the respective salts. The solutions were all, therefore, 0.262 M with respect to sodium malate and of various normalities with respect to the salts.
Effect of Salts on Sodium Malate (%ID (MID
Sodium malate K NaCl 3N NaCl 5s NaCl
- 8.82' -7.69' -5.88' -3.39'
- I 5 .7o0 -13.69' -10.46' - 6.04'
NNaBr 3h'NaBr SNXaBr
(a)D -7.46' -5.65" -3.62'
(MID -13.28'
-10.06' - 6.48'
I n this table the effect of each mol of salt is to decrease the specific rotation of sodium malate about one degree. A very extensive investigation of this effect was made by Stubbsl who found that the effect of such salts (in more dilute solutions) was an additive one which could be attributed to the ions separately, the positive and the negative ions falling into series of similar nature to other series known. In order of effectiveness these were; (best) Cs, Rb, K, S a , XH4, Li (least), and (best) I, Br, C1, X03, 1/aS04 (least,), with calcium and barium showing very large effects and zinc and mercury anomalous effects. These effects, Stubbs believed could only be explained by some power of the inactive electrolytes of influencing the asymmetry of the active molecules without entering into combination with them. It seemed probable to him that the mode of influence might be connected with the sensitiveness of the hydroxyl group of malic acid. More recently Darmois2 has made a similar study of the effect of salts on tartaric acid and has reviewed several hypotheses regarding the cause of this influence returning finally to the theory of two forms of tartaric acid which can not a t present be determined. Markedly abnormal is the behavior of the bivalent metallic salts, especially barium and calcium. The chlorides and nitrates of these metals produce about three times the effect of an equivalent amount of the univalent salt. Stubbs comments: "It is very significant that, as appears from the conductivity tables, t h e dissociation of barium nitrate in aqueous solutions is abnormally low; for, whilst barium and calcium chlorides show practically equal degrees of dissociation in N/z solutions, that of barium nitrate is only about five-sixths that of calcium nitrate. A connexion thus appears J. Chem. SOC.,99,2265 (1911). Ann. Phys., 10,70 (1928).
918
WILDER D. BANCROFT AND HERBERT L. DAVIS
to exist between the degree of dissociation of a salt and its influence on the rotation of malic acid. “The most remarkable fact shown by Table IV is the great influence exerted by salts of barium and calcium, especially when it is remembered that in equal equivalent concentrations there is only half an atom of these elements present to one atom of the alkalis.” A table of various bivalent salts leads him to the further conclusion: “It follows that the large influence of barium and calcium salts is not merely dependent on the valency of the metal.” I n general the bivalent salts behave differently from the univalent salts. “A striking illustration is the case of zinc sulphate, where the effect of n = 1/4 (a twenty per cent solution of l-malic acid containing 1/4 equivalent of salt) is actually zero, that when n = l being more than a degree. It thus appears that the first addition of zinc sulphate produces a negative effect, making the solution more levo; and that, as further quantities are added, the influence attains a negative maximum, passes through zero, and becomes positive. The case of mercuric nitrate, if comparable, is more remarkable still. The figures (for n = 1/4, A = -3.36’, and for n = I , A = -3.58”, A being the change in rotation produced) suggest that the initial large negative influence reaches a maximum between the concentrations studied, and that further additions of salt would probably influence the rotation on a dextrosense.” Schneider had shown that while inactivity on dilution in the case of the alkali malat,es entered in fairly concentrated solutions containing from z j to 60% of the salts, the data for barium malate are quite different. Percent barium malate Specific rotation
I
.96
-2.58”
4.99 +4,69O
8.50 +8.ojo
9.38%
S8.18’
This would indicate an inactive solution contained about 3% of barium malate. Hence calcium and barium salts as added to malic acid seem markedly to influence the formation of the dextro (the concentrated solution) form and the same thing is true of the barium malate as such. A similar phenomenon is reported by de Malleman’ for tartaric acid. Additions of concentrated solutions of calcium chloride affect enormously the rotation of d-tartaric acid, diethyl tartrate, (in water and in alcohol) and sodium hydrogen tartrate, making each solut,ion strongly levorotatory, or favoring the concentrated solution form, as it should be remembered that while dilute solutions of tartaric acid are dextrorotory the ethylene oxide form of this acid will be levorotatory. In addition to the changes listed above, malic acid shows several other abnormalities. With rise in temperature a levorotatory solution of malic acid becomes more strongly so, while a dextrorotatory solution may show levorotation at higher temperatures. As was pointed out above, the same is true of the supercooled solid. I t is clear that rise in temperature favors the ‘Compt. rend., 173, 474 (1921).
THE OPTIChL ROTATION OF MALIC A C I D
9’9
formation of the levorotatory form. This form corresponds to the ket,o form in the usual keto-enol tautomerism and rise in temperature usually favors this form. The same situation (with signs reversed) prevails in tartaric acid. Increase in temperature favors the formation of the dilute-solution normal form in both cases. Again this effect is much too large to be explained on the dissociation hypothesis. I t has, therefore, been shown that although malic acid is dissociated as a weak acid this ionization is quite inadequate to explain the numerous abnormalities in the optical rotations of malic acid and its derivat,ives. More attention has been given to this explanation of the phenomena than will be given to the remaining explanations because of the apparent. simplicity of this one and the number of times it has been mentioned in the literature. .Inother popular explanation has been founded on the assumption that in concentrated solutions there are formed dextrorotatory semi-crystalline aggregates of the malic acid molecules. Landolt showed and Lowry‘ has more recently demonstrated that there is no direct relation between the degree of polynierization of a solute and its optical rot,atory power. The work of Lowry indicates that there are solutions of ethyl tartrate in various solvents in which the ester is polymerized increasingly with concentration, and the specific rotation changes but little with change in concentration; while in other solvents freezing-point measurements indicate that there is practically no polymerization, and the rotations change markedly with dilution. Lowry and Cutter believe their facts are in accord with three propositions: * ‘ ( I ) the ester exists in isomeric dextro and levoforms; ( 2 ) the levo form tends to be produced in solvents which favor polymerization; (3) this polymerization, however, usually produces an increased dextrorotation or a decreased levorotation.” I t is clear, then, that for ethyl tartrate polymerization is inadequate, all varieties of relationships being known. The behavior of malic acid is similar. The fact that malic acid crystallizes with difficulties under the best conditions indicates a probable absence of crystal aggregates. Raoult showed that dilute aqueous solutions of malic acid gave a normal lowering of the freezing-point. I n addition to this Nasini and Gennari showed that the freezing point depression of solutions containing up to z 4 . j grams of malic acid in I O O g r a m of water was still normal and indicated no sign of polymerization. Rut there always esists*somesuspicion of molecular weight determinations in such concentrated solutions since the theoretical treatment of such colligative properties as are used is limited in most cases t o the dilute solutions. It was shown by Bancroft that if there is a large positive heat of dilution, the apparent molecular weight will come out smaller than it actually is, so that a polymerization might thus be masked. Rut Thomsen found that the heat of dilution of tartaric acid is negative. We have found the same thing to be true of malic acid. This, therefore establishes the complete validity of the freezing-point dpterniination as indicating no polymerization in aqueous solutions of malic acid showing marked abnormalities in their optical behavior. l
Lowry and Cutter: J. Chem. SOC., 125, 1 4 6 j i I 9 2 4 l .
920
WILDER D. BANCROFT AND HERBERT L. DAVIS
Nasini and Gennari report also that they kept two identical solutions of l-malic acid, one at o°C and one at 8o°C for three hours and then read their rotations a t zo°C. The rotations were the same showing that temperature produced no permanent effect and that to each temperature there corresponds a certain equilibrium state which is attained quickly. The abnormal properties of malic acid can not be explained on the assumption of a formation of hydrates varying with the concentration. Many years ago, Nernstl demonstrated that, according to the mass law, the ratio of hydrated to non-hydrated molecules is independent of the concentration.
A
+ n HzO = A.n HzO.
Since (H20) is constant;
On this basis hydrate formation would not cause the specific rotation of an optically active solute in water to change with dilution. But this demonstration is not so conclusive as it appears, for it leaves out of consideration the relative solubilities of the two forms and is valid only when these are identical. If, as is usually the case, the hydrated form is much more soluble than the non-hydrated form, more of the hydrated form will result from dilution than the above equation provides and that demonstration loses its significance. A similar remark might be made of various other phenomena to which mass law expressions have been applied without due attention being paid to the solubility effects involved. A number of other objections to the hydrate theory were summarized by Nasini and Gennari, who concluded that this hypothesis seems improbable here. Bell had shown that, on solution of tartaric or of malic acids, the temperature changes indicate no hydrate formation; further, in order to explain the complex changes, one must assume a very large number of hydrates and this is not probable, judging from what we know of true and definite hydrates. According to Bell, this hypothesis is inadequate for tartaric acid, since Biot observed for the molten acid the same change in rotatory power with change in temperature which he had already found in the most concentrated solution. The cryoscopic determinations also contradict this theory for, if hydrates form, the molecular depression of the freezing point should vary, decreasing with increase of concentration; actually, it remains very constant. As has been mentioned, the supercooled malic acid changes from levorotation to dextrorotation as the temperature decreases, exactly as do the concentrated solutions of malic acid in water. The malic acid glass can scarcely be undergoing a reversible hydration and dehydration. Likewise malic acid in alcohol behaves on dilution quite as it does in water, showing greater levorotation in the alcoholic solutions. If the non-hydrated form were the dextrorotatory form, the alcoholic solutions should be more dextrorotatory than the aqueous solutions. IZ.physik. Chem.,
11, 345 (1893).
THE OPTICAL R O T S T I O S OF MALIC ACID
92 1
Stubbs considered hydrate formation when he investigated the effect of salts on malic acid, pointing out that hydrate formation either by the salts or the malic acid would be equivalent to a concentration leading to dextrorotation. But the salt effects were too large to be thus explained, for barium chloride a t high concentration gives several times as large a dextrorotation as would be observed in the fused anhydrous malic acid, and salts with the greatest affinity for water (LiCl) actually exert the least influence. R e may conclude therefore, that neither the rotation-dilution changes of malic acid nor the effects of salts can be explained by an assumption of hydrate formation. The formation of a dextrorotatory lactone such as is believed to take place in the case of lactic acid is not a sufficient hypothesis to explain the malic acid rotations. I n the salts and esters the hydrogen of the carboxyl group is replaced, with consequent loss of acidic character and, therefore, loss in capacity to combine with the alcoholic hydroxyl group to form the lactone. Severtheless, the salts and esters exhibit the same large changes in rotation as is shown by malic acid itself. In the case of the salts we can not rule out the possibility of lactone formation from the ion according to a mechanism proposed by Holmberg. G.CO.CH2.CH(OH).CO.D = CO CH2,CH CO.0
LOA
+ OH
But this can surely not take place in alcoholic solutions of the esters. The dextrorotatory form of I-malic acid cannot be d-malic acid itself, formed reversibly by the action of foreign substances or the process of dilution. If d-malic acid could be thus formed, a solution of inactive malic acid containing equivalent amounts of d- and I-malic acids would become dextrorotatory on addition of acids, bases or salts which cause I-malic acid to become less levo- or more dextrorotatory. Hydrochloric acid or sodium hydroxide impart no activity to a solution of dl-malic acid. We are forced to conclude that these inactive substances do not favor the formation of d-malic acid from I-malic; but that they have an equal and opposite effect on the optical antipodes. This will be evident also from a consideration of the rotatory dispersion of malic acid. 3 s is usually the case, the rotation of malic acid depends on the wave-length of light employed. There is a close parallelism between refraction and rotation, and in both light of the shorter wave-length is affected t o the greater extent. This represents normal dispersion. But malic acid and tartaric acids and their common salts and esters possess anomalous dispersion in which their rotations pass through maxima a t certain intermediate wave-lengths instead of increasing regularly. According to the data of Nasini and Gennari, concentrated solutions show a stronger rotation of blue light than of red. With decrease of concentration, dextrorotation of these solutions also decreases, until certain solutions are levorotatory to red light and dextrorotatory to blue light. Inactivity toward dark blue light occurs
022
WILDER D. BAXCROFT .4ND HERBERT L. DAVIS
a t 1 6 7 ~malic acid. At this point the maximum rotation is shown toward yellow light. As dilution continues the solutions once more turn blue light through the largest angle. Such phenomena are usually interpreted as indicating the presence in the solution of two oppositely rotatory substances, each having normal but different dispersions. Lowry' believes this is not necessarily true but it appears to be true in most cases. There are no known cases in which the dispersions of two antipodes are different. It follows from this that a mixture of unequal quantities of two antipodes, might have rotations that vary with the wave-length but there can be no maximum or minimum as make their appearances in malic acid. Further, if d-malic acid could have a different dispersion from 1-malic acid, the dl-malic acid should show some activity. There is no observable activity in the D light) and the possibility seems remote that the antipodes might have the same rotations for the D light and different rotations for all the other wave-lengths. Some General Observations on Tautomerism The treatment outlined in this paper has been based on the assumption that in tautomerisms such as are here postulated, the mobility of the hydrogen atom is greater than that of any other atom or group of atoms. This has been demonstrated in some of the examples cited, in which replacement of the mobile hydrogen by some other atom or group resulted in a compound which showed very much less tendency to tautomeric change, as indicated by the smaller rotation-dilution changes. But this is not necessarily true and a final word of qualification may be added, providing another possible explanation for the same phenomena, and, at the same time, additional proof that what we have t o do with in the malic and tartaric acids is a true case of tautomeric change. Freundlerz prepared several esters of the substituted tartaric acid series in which the alcoholic hydrogens were replaced by acid groups, as for example, diethyl-diacetyltartrate. These esters were examined polarimetrically in various organic solvents which were divided into t'hree principal groups. The first of these solvents appear to have little if any effect on the optical activity of the solute ester, solutions of all concentrations showing practically the same specific rotatory power, and this value being not markedly different from that of the pure liquid ester: this group included acetone, alcohol, and ethylene bromide, The second group of solvents raised the algebraic value of the rotations, acetic acid and carbon disulphide being included here. Finally there was a group of solvents, including benzene, toluene, chloroform, bromoform, and carbon tetrachloride which lowered the specific rotations, in many cases causing the esters, which were nearly all dextrorotatory in the free liquid state, to show levorotation in these solvents. These classifications are not rigid and do depend somewhat upon the character of the esters employed. Freundler accepted the first group of solvents as normal and fulfilling J. Chem. Soc., 1929, 2861. Ann. Chim. Phys., (7) 4, 235 (1895).
T H E OPTICAL ROTATION OF MALIC ACID
923
Biot's law of the constancy of rotation in the absence of any interaction between the solute and the solvent. He was not very successful in his attempt to explain the abnormal rotations on the basis of polymerization or depolymerization of the ester, solvate formation, or a kind of dissociationof theester. It now appears certain that what Freundler was dealing with was actually a variation of the mobility of these acid groups in the various esters and in the various solvents. I n other words, there is in these tartaric acid derivatives a tautomeric change such as has been outlined in this paper for malic acid and its derivatives. It has been demonstrated by the rotations in water that this change is less in the case of the compounds in which the hydrogen is replaced by methyl, ethyl, or propyl groups. It might be presumed that the change would be greater if the hydrogen were replaced by negative groups but the constancy of acetylmalic acid does not agree with this. No definite statement can be made until more experimental work has been done on the related compounds. I n all these compounds there will be in the free state an equilibrium between the normal straight form and the oppositely-rotatory, ethylene oxide., form. Those solvents which have lit'tle or no effect on the rotations must be such that they dissolve the two forms in just about the sameproportions as those in which they occur in the free state. Those solvents in which the normal form is much more soluble than the oxide form will exhibit changes of rotation and the more dilute the solutions, the farther removed will be the specific rotation from that of the solvent-free substance. Those solvents in which the oxide form is more soluble will cause the rotation of the compound to be displaced in the opposite sense algebraically, and the greater the dilution, the greater the abnormality. An example of this is found in tartaric acidwhich shows (for C = 5) : in water [a], = 15.0"; in alcohol-benzene -4.0'. While this aspect of tautomerism, involving groups other than the hydrogen atom, has not been emphasized, there are many instances of it in the literature. Cohen' gives numerous examples of the migration of hydrocarbon radicals from which w e select a few which are relevant. On p. 398 is found; "McKenzie and his co-workers2 have made the interesting observation that certain ap-amino alcohols when acted upon by nitrous acid undergo similar transformations to the semipinacolinic change, which he termed 'semipinacolinic deamination'.
+
(CsHs), C - CH.CSHi
I
1
OH S H ?
Hh-02
---+
('6Hb \C CeHj
- CH,CfiHb
I t will be noticed that in this reaction the amino group is detached and any transference only involves the radicals attached to the carbinol carbon In "Organic Chemistry", 2, (1928). J. Chem. Soc., 123, 79 (1923); 125, 848, 2148 (1924); (19261, j i g . rend., 180, 145;Orekhoff and Foger: i o (1925).
Luce: Compt.
WILDER
924
D.
BANCROFT AND HERBERT L. DAVIS
this way the study of the preferential migration of M e r e n t radicals is determined more easily and accurately. By applying this method it was shown that phenyl migrates more readily than methyl, and naphthyl and anisyl more readily than phenyl.” On p. 404 are found examples of the migration of ethyl groups from ethoxy groups and of acetyl groups. “Claisenl found that isoacetophenone ethyl ether when boiled under pressure changes into phenylpropyl ketone. C3HsC(OC2Hr,) :CH2 + C6Hs.CO.CH2CZHs Isoacetophenone ethyl ester Phenylpropyl ketone He also showed that the acetyl derivative of hydroxycrotonic ester (from acetoacetic ester, acetyl chloride, and pyridine) was transformed by means of potassium carbonate and a little acetoacetic ester, or by sodium acetoacetic ester into diacetoacetic ester.2 CH3 CHI
1
C.OC.OCH3
CO
II I
CH.COCH3
I I
CH
COOCzHs COOCzHs The corresponding alkyl derivatives do not undergo this conversion.” This last statement can not be true. It must mean that the positive I
methyl group migrates from a -COCH3 group less readily than a negative I
I
acetyl group migrates from a similar -C.O.COCHa group. This could have I
been predicted from what h s been said above. Immediately following the above quotation, Cohen continues: “Acetophenone O-ben~oate,~ on the other hand, is converted in much the same way by the action of metallic sodium and a little acetophenone into the sodium compound of dibenzoylmethane.” C~H&O(CO.C~HE,) :CHz * ‘&H~CO~CHz~COCsHs “A reaction of a character eimilar to the foregoing is the conversion of the acetyl derivatives of the polyhydric phenols into acetyl derivatives of the cyclohexanones when heated with zinc chloride.”* CH.COCH3
CH3C0.~~~~(3COCH3
O C A co ---t
0
CH3CO.HC CO.COCH3 Triacetyl phloroglycinol 2
a 4
Ber., 29, 2931 (1896). Ber., 33, 3778 (1900). Claisen and Haase: Ber., 36, 3678 (1903). Heller: Ber., 42, 2736 (1909); 45, 418 (1912).
CH.COCH3
co
Triacetyl cyclohexatrione
T H E OPTICAL ROTATION OF MALIC ACID
925
It is clear, then, that not only hydrogen migrates but also positive or negative groups replacing hydrogen may participate in dynamic isomerism. In the cases considered, it appears that the positive groups migrate less readily and the negative groups more readily than the hydrogen atom. This must, however, depend upon the character of the groups attached to the carbon atoms in question and upon the solvents employed. This effect of the solvent on the ordinary keto-enol tautomerism has been studied extensively, Certain other isomeric changes have likewise been investigated by Dimroth (Cohen, 11, 378). “He determined the relation between the solubilities and the velocity of transformation of phenylhydroxytriazole carboxylic ester and its amino derivatives in a great variety of solvents.’ /C(NHCBH~) >COOC~H~ C6N %COOC,H, HP\’ h- = h\ X = N Yeutral form Acid form
..
