# The New International Encyclopædia/Stereo-chemistry

Edition of 1905. See also Stereochemistry on Wikipedia; and the disclaimer.
​STEREO-CHEMISTRY. A branch of chemistry dealing with those cases of isomerism that cannot be explained by the doctrine of the linking of atoms, and explaining those cases on the assumption that the combining forces of an atom act in certain definite directions in space. Isomerism (i.e. the existence of compounds having the same qualitative and quantitative composition and the same molecular weight, yet differing more or less in their properties) and the doctrine of the linking of atoms (the structural theory) have been discussed in the article Carbon Compounds, which should be read in connection with the present sketch.
Optical Isomerism. Most of the cases not explained by the doctrine of the linking of atoms are presented by compounds identical in all their chemical and physical properties except the power of rotating the plane of polarized light. It is well known that this power is possessed by a number of crystalline substances in the solid state, and that every such substance can be obtained in two ‘enantiomorphous’ crystalline forms, rotating the plane of polarized light through equal angles but in opposite directions. But when melted or dissolved such substances usually lose that power completely—which shows that their optical property is peculiar, not to their nature, but to the particular crystalline form which they assume in the solid state. These are not the substances that stereo-chemistry has to deal with: such substances, inasmuch as they lose their difference of optical rotatory power with their crystalline form and are therefore identical in the liquid, gaseous, or dissolved state, cannot be considered as different chemical individuals, and hence cannot form the subject of a theory of chemical compounds. Cases of optical isomerism proper are presented by substances retaining or acquiring their difference of optical rotatory power in the liquid, gaseous, or dissolved state.
In 1874 Le Bel and Van ’t Hoff discovered, independently and almost simultaneously, that all optically active compounds, and only optically active compounds, contain one or more ‘ ​asymetric’ carbon atoms, i.e. carbon atoms directly linked to four atoms or groups of atoms different from one another. The following formulas, containing asymmetric carbon atoms (denoted by an italic C), represent optically active compounds:
| Lactic acids | Malic acids |
| Mandelic acids |||
On the contrary, formulas like that of propionic acid,
which contains no asymmetric carbon atom (i.e. no atom combined with four different atoms or groups), have in no case been found to represent optically active compounds. The relation between the optic rotatory power and the asymmetric carbon atom must therefore form the cornerstone of any explanation of optical isomerism that might be advanced. Altogether three different explanations suggest themselves as possible: (1) the assumption that the four valencies of the carbon atom are unequal and that cases of isomerism may result from different distributions of the four atoms or groups combined with the carbon atom, among its different valencies; (2) the assumption that the atoms or groups combined with the carbon atom are in constant motion around it and that the molecules of optically different compounds may be made up of the same atoms or groups in different motions around the carbon atom; and (3) the assumption that the molecules of different compounds may be made up of the same atoms or groups, similarly linked to the carbon atom, but differently arranged in space around it. The first of these assumptions compels us to recognize the possible existence of isomers that are positively known to be impossible. For instance, if the assumption were correct, two different nitro-methanes would be possible; yet a systematic experimental investigation carried out by Henry showed that nitro-methane can exist in one form only. The second of the above assumptions is altogether incapable of either purely theoretical development or systematic correlation with facts, and must therefore be abandoned. The third assumption, viz. that the difference between optical isomers is due to differences in the configuration of the atoms in their molecules, presents itself, therefore, as the only possible explanation. Furthermore, even this explanation must first of all discard the hypothesis of the arrangement of atoms in a plane. Indeed, were the plane graphical formulas, as we ordinarily write them, true to reality, then, for instance, two methylene chlorides would be possible, the configurations of whose atoms would be represented by the following formulas:
Yet only one methylene chloride is possible. If the valencies of the carbon atom were assumed to be distributed, in the plane, not at equal angles, but, say, as in the symbol
then the number of theoretically possible yet really non-existing isomers would be even greater. Considerations of this nature have led to the conclusion that if optical isomerism is to be explained, it is necessary to assume that the four atoms or groups held by an asymmetric carbon atom are situated at equal distances from the carbon atom and at equal distances from one another—which is equivalent to assuming that the asymmetric atom is situated at the centre of a regular tetrahedron, and the four different atoms or groups held by it are situated at the four corners of the tetrahedron. This, then, is the fundamental hypothesis of stereo-chemistry. Its application to the study of isomerism is very difficult to explain or to grasp without the use of models. A crude but sufficient form of model may be readily made in a few minutes from pasteboard, by cutting out four equal equilateral triangles and fastening them together to form a regular tetrahedron, by means of strips of gummed paper. Small slips of paper of different colors may be used to represent the four different atoms or groups and may be fastened to the corners by means of pins. With the aid of two such models it is easy to demonstrate the following cases: (1) With three slips of paper of one color and one of another color, only one arrangement is possible, which corresponds, for instance, to the fact that only one nitro-methane, ${\ce {CH3(NO2)}}$, can be obtained. (2) With two slips of paper of one color and two of another color, again only one arrangement is possible, which corresponds, for instance, to the fact that only one methylene chloride, ${\ce {CH2Cl2}}$, can be obtained. (3) With two slips of paper of one color, one slip of another color, and one of a third color, again only one arrangement is possible, which corresponds, for instance, to the fact that only one propionic acid, ${\ce {CH2(CH3)(COOH)}}$, can be obtained. (4) With four slips of different colors two different arrangements are possible, which corresponds to the fact that only molecules containing an asymmetric carbon atom, i.e. one linked to four different atoms or groups, can be different in spite of being made up of the same atoms linked together in the same manner. The two models will, in this case, be like an object and its image in a mirror, or like the right hand and the left hand; turn both hands palm downward and it is impossible to superpose them so that the corresponding fingers touch—the thumb of the right hand will touch, not the thumb, but the little finger of the left hand, etc. Thus the models will illustrate the difference between the two optically active lactic acids, malic acids, or mandelic acids (see above); or, in general, any pair of optical isomers whose molecules contain one asymmetric carbon atom. As an instructive example it may be demonstrated, by means of the ​models, why only one acetic acid, ${\ce {CH3(COOH)}}$, is possible; why only one mono-chlor-acetic acid, ${\ce {CH2(Cl)(COOH)}}$, is possible; why only one di-chlor-acetic acid, ${\ce {CHCl2(COOH)}}$, is possible; why only one tri-chlor-acetic acid, ${\ce {CCl3(COOH)}}$), is possible; why two optically isomeric chloro-bromo-acetic acids, ${\ce {{\mathit {C}}(H)(Cl)(Br)(COOH)}}$, are possible; and why two optically isomeric chloro-bromo-fluor-acetic acids, ${\ce {{\mathit {C}}(Cl)(Br)(F)(COOH)}}$, are possible.
As already pointed out above, optical isomers are invariably found to possess precisely the same chemical and physical properties and to differ only with regard to the direction in which they rotate the plane of polarized light. The question now suggests itself, How can such isomers be separated from each other when mixed? This problem is so much the more important because all reactions by which compounds with asymmetric carbon atoms may be produced from compounds containing no such atoms cause the simultaneous production of both optical isomers in precisely equal quantities; so that a separation is required whenever optically active compounds are to be prepared artificially (in nature either one or the other of a pair of optical isomers is often found isolated). Three methods have thus far been found for effecting the separation. First, it is possible, in many cases, and under certain conditions of temperature, to separate the isomers mechanically—in those cases, namely, in which the two crystallize from their solutions separately. In all such cases the two isomers are found to form enantiomorphous crystals. Below, or sometimes above, the point or interval of temperature at which this takes place, the two isomers usually crystallize together, forming a double compound, the so-called ‘racemic’ modification of the given compound. The racemic modification is optically inactive because its two components tend to rotate the plane of polarized light to the same extent in opposite directions. The second method of separating optical isomers is applicable only to acids and bases. If a mixture of two optically isomeric acids is treated with an optically active base, two salts result differing more or less considerably in solubility, and therefore capable of being separated by fractional crystallization. The result is similar when a mixture of two optically active isomeric bases is treated with an optically active acid. Finally, the third method is based on the fact that certain processes of fermentation often destroy one of the optical isomers and leave the other intact. Thus, levo-glucose may be prepared by subjecting to fermentation its mixture with dextro-glucose, the latter alone being affected by the fermentation. The reason of such facts is not yet understood. It has been assumed by some that the living organisms (e.g. Penicillium glaucum) causing fermentation are capable of discriminating, by a sort of instinct, between the isomers, and, while feeding on one, reject the other. But the lifeless enzymes (q.v.) obtained from ferments have been shown to exercise the same action as the ferments themselves; and hence the peculiar action of the latter may be assumed to be due to the purely chemical properties of their enzymes.
Passing now to the consideration of compounds whose molecules contain more than one asymmetric carbon atom, the most important case to be mentioned is that of tartaric acid, ${\ce {(COOH){\mathit {C}}(H)(OH).{\mathit {C}}(H)(OH)(COOH)}}$, with two asymmetric carbons in its molecule. By the use of models like those mentioned above, it is easy to convince one’s self that three different arrangements are possible: (1) a right-handed arrangement of the groups around either of the asymmetric carbons; (2) a left-handed arrangement of the groups around either of the asymmetric carbons; (3) a right-handed arrangement around one, and a left-handed arrangement around the other asymmetric carbon. Corresponding to these are the well-known dextro-rotatory, levo-rotary, and inactive modifications of the acid, the last named being inactive because one-half of its molecule rotates the plane of polarized light to the same extent in one direction as the other half does in the opposite direction. Besides these there is the racemic modification (‘racemic acid’), which is a double compound of the dextro-rotatory and levo-rotatory tartaric acids (q.v.). The compounds containing more than two asymmetric carbon atoms include the sugars (q.v.)—an important class of compounds whose theory could not have been developed, and many of which could hardly have been discovered without the concepts of stereo-chemistry.
Geometrical Isomerism. It may be seen from the preceding paragraphs that the fundamental hypothesis of stereo-chemistry, viz. that the valencies of a carbon atom act symmetrically around it in space, while indispensable for correlating optical isomers, also throws additional light on the phenomena of chemical isomerism proper. Take, for example, again the case of methylene chloride, ${\ce {CH2Cl2}}$. Were optical isomerism unknown and the stereo-chemical hypothesis non-existent, the question as to why only one modification of this compound is possible would be answered by pointing out that the four carbon valencies are identical and that, hydrogen and chlorine atoms being univalent, only one mode of linking the atoms is possible. If it were further asked, “But how do we know that two methylene chlorides might not exist, in whose molecules the atoms are linked similarly, but arranged differently?”—chemists would answer: “Of course, such a state of things is not inconceivable: only in all the innumerable cases thus far discovered, the doctrine of the linking of atoms is sufficient, the number of known isomeric compounds never exceeding the number of possible modes of linking; and so we deem it unnecessary to enter into speculations as to the arrangement of atoms in space.” From the standpoint of stereo-chemistry the answer is thorough: only one methylene chloride is possible, (1) because the four valencies of carbon are identical; (2) because only one mode of linking the atoms is possible; (3) because only one arrangement of the atoms in space is possible, as may be readily demonstrated by the use of tetrahedron models.
It is, therefore, clear that stereo-chemistry not only explains, and hence permits of foreseeing, all possible cases of optical isomerism, but also explains thoroughly why more cases of chemical isomerism than are explained and foretold by the doctrine of the linking of atoms are not possible. But stereo-chemistry has still another important application. Its fundamental hypothesis applied to the so-called ‘unsaturated’ compounds ​(see Carbon Compounds) leads to a clear explanation of cases of isomerism which, again, cannot be explained by the doctrine of atomic linking alone. In the simplest class of unsaturated compounds one carbon atom is united by two valencies to another carbon atom. In stereo-chemistry this means that two carbon tetrahedra have an edge in common, the four atomic groups held by the two carbons being situated at the four free corners of the tetrahedra. Take, for example, the case of two carbon atoms united by a double bond and holding two hydrogen atoms and two carboxyl (${\ce {COOH}}$) groups. In this case the doctrine of the linking of atoms recognizes the possibility of two isomeric modifications, viz.:
| | Methylene-malonic acid |
| and | |
| | Maleic and fumaric acids |
Stereo-chemical doctrine recognizes that with the second of these modes of linking two different arrangements in space are possible, as may be seen from the accompanying diagram, and
| Maleic acid | Fumaric acid |
better still by the use of models. As a matter of fact, three unsaturated acids ${\ce {C3(H2)(COOH)2}}$ are known, viz. methylene-malonic acid characterized by the first of the above modes of linking, and two acids—maleic and fumaric—both characterized by the second mode of atomic linking, and differentiated from each other by the different configuration of their atoms. Optical activity is of course out of question, because none of the molecules under consideration contains an asymmetric carbon atom. But corresponding to the difference in configuration are certain differences in the chemical behavior of maleic and fumaric acids, although the close relationship between the two is indicated by the great readiness with which they are transformed into each other. The most important difference between the two consists in the fact that maleic acid readily forms an anhydride, its two carboxyl groups losing the elements of water and becoming joined together, thus:
| | $-$${\ce {H_2O}}$$=$ | |
| Maleic acid | | Maleic anhydride |
Fumaric acid, on the contrary, has no anhydride of its own. This indicates that in maleic acid the two carboxyl groups must be nearer together than in fumaric acid, and therefore the first of the above two stereo-chemical formulas is assigned to maleic, the second to fumaric acid. See Fumaric and Maleic Acids.
As to compounds with triple bonds in their molecules (see Carbon Compounds), the verdict of stereo-chemistry is that no more isomers are possible than can be foreseen by the doctrine of atomic linking. This, too, may be best demonstrated by means of models.
History. In conclusion it may be mentioned that the optical rotary power of a substance in the non-crystalline state (sugar in solution) was first observed by Biot in 1815. The optically isomeric tartaric acids were thoroughly investigated by Pasteur, who in 1860 discovered the three known methods of separating such isomers (see above). Ten years later Wislicenus studied the isomeric lactic acids, and in a memoir published in 1871 expressed the view that the doctrine of atomic linking was no longer sufficient for the purposes of organic chemistry. Wislicenus’s remark attracted the attention of Van ’t Hoff, who advanced the stereo-chemical theory of optical isomerism in 1874. Meanwhile Le Bel, in Paris, had undertaken to continue the work of Pasteur, and soon independently arrived at the same conclusions as Van ’t Hoff. Remarkably enough, Le Bel’s and Van ’t Hoff's memoirs appeared within one month. The theory of geometrical isomerism was worked out by Van ’t Hoff about 1878. At present stereo-chemistry forms quite an extensive science, and its theories, to which no exception has yet been found in the case of carbon compounds, are being gradually extended also to the compounds of nitrogen. Consult: Wislicenus, Ueber die räumliche Anordnung der Atome, etc. (Leipzig, 1887); Hantzsch, Grundriss der Stereochemie (Breslau, 1893; French trans., Paris, 1896); Van ’t Hoff, Die Lagerung der Atome im Raume (Brunswick, 1894); Bischoff, Handbuch der Stereochemie (Frankfort-am-Main, 1893). Consult also the works on theoretical and organic chemistry recommended in the article Chemistry. See Chemistry; Carbon Compounds; Lactic Acid; Tartaric Acid; Fumaric and Maleic Acids; Valency.