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Related to Isomerism: optical isomerism, structural isomerism, geometric isomerism, Conformational isomerism
(of chemical compounds), a phenomenon that consists in the existence of substances identical in composition and molecular weight but differing in structure or arrangement of the atoms in space and, therefore, in chemical and physical properties. Such substances are called isomers.
Isomerism was discovered in 1823 by J. von Liebig, who showed that the silver salt of fulminic acid, Ag—O—N=C, and silver isocyanate, Ag—N=C=0, were identical in composition but had completely different properties. The term “isomerism” was proposed in 1830 by J. Berzelius. Isomerism is particularly prevalent among organic compounds. The phenomenon of isomerism was successfully explained by the theory of chemical structure developed in the 1860’s by A.M. Butlerov.
A distinction is made between structural isomerism and spatial isomerism (stereoisomerism). Structural isomers differ in the sequence of interatomic bonds in the molecule; stereoisomers differ in the positions of the atoms in space, with identical sequence of interatomic bonds.
Structural isomerism. Structural isomerism is divided into a number of varieties. Skeletal isomerism is caused by a difference in sequence of the bonds between the carbon atoms forming the skeleton of the molecule. Thus, there can be only one acyclic saturated hydrocarbon with three carbon atoms—propane (I). For hydrocarbons of the same type but with four carbon atoms, there are two forms, n-butane (II) and isobutane (III); and for those with five carbon atoms there are three forms, n-pentane (IV), isopentane (V), and neopentane (VI):
The hydrocarbon C20H42 can have 366,319 isomers.
Position isomers are caused by a difference in position of a reactive group (functional group or substituent), with identical carbon skeletons of the molecules. Thus, there are two isomeric alcohols, n-propyl alcohol (VII) and isopropyl alcohol (VIII), corresponding to propane:
Position isomerism is important among aromatic compounds, because the position of substituents in the benzene ring is the main factor that determines the reactivity of a substance. For example, o-dinitrobenzene (IX) and p-dinitrobenzene (X) react readily with ammonia, but m-dinitrobenzene (XI) does not.
For ethers, sulfides, and amines of the aliphatic series there is a special kind of isomerism, metamerism, which is caused by different positions of the heteroatom in the carbon chain. For example, methyl propyl ether (XII) and diethyl ether (XIII) are metamers:
The term “metamerism” is very rarely used.
Isomerism of unsaturated compounds can be caused by different positions of the multiple bond, such as in butene-1 (XIV) and butene-2 (XV) or vinylacetic (XVI) and crotonic acids (XVII):
In most cases structural isomers combine the features of skeletal and position isomerism, contain different functional groups, and belong to different classes of substances, so that they differ much more than the isomers of compounds of the same type considered above. For example, the following are isomers: propylene (XVIII) and cyclopropane (XIX); ethylene oxide (XX) and ace-taldehyde (XXI); acetone (XXII) and propionaldehyde (XXIII); methyl ether (XXIV) and ethanol (XXV); and allene (XXVI) and methylacetylene (XXVII).
A special form of structural isomerism is tautomerism (equilibrium dynamic isomerism), which is the existence of compounds in two or more isomeric forms that readily undergo
interconversion. Thus, acetoacetic ester exists as an equilibrium mixture of keto (XVIII) and enol (XXIX) forms:
Spatial isomerism. Spatial isomerism is subdivided into two types, geometric isomerism (or cis-trans isomerism) and optical isomerism. Geometric isomerism is peculiar to compounds containing double bonds (C=C, C=N, and so on) and nonaromatic cyclic compounds and is due to the impossibility of free rotation of atoms around a double bond or in a ring. Under such conditions, substituents may be on the same side of the plane of a double bond or ring (cis-position) or on different sides (transposition). The concepts of cis- and trans- usually apply to a pair of identical substituents, and if all the substituents differ, they apply arbitrarily to one of the pairs. Examples of geometric isomers are the two forms of ethylene-1,2-dicarboxylic acid—the cis- form, or maleic acid (XXX), and the trans- form, or fumaric acid (XXXI); others are the cis- and trans- forms (XXXII and XXXIII, respectively) of cyclopropane-1,2-dicarboxylic acid:
The terms syn- and anti- are often used instead of cis- and trans-, respectively, to denote the isomers of compounds with C=N or N=N double bonds. Thus, in the syn-benzaldoxime molecule (XXXIV), the hydrogen on the carbon atom and the hydroxyl on the nitrogen lie on the same side of a plane passing through the C=N bond, whereas in the antt’-benzaldoxime molecule (XXXV), they lie on different sides:
Geomefric isomers usually differ essentially in physical properties (boiling and melting point, solubility, dipole moment, and thermodynamic properties). Properties of geometric isomers— maleic and fumaric acids—are given in Table 1.
Maleic acid (cis-form)
|Table 1. Some physical properties of maleic and fumaric acids|
|Melting point (°C) ...................||130||286|
|Solubility in 100 g of water at 20° (g) ...||78.8||0.7|
|Dissociation constant at 25° (k1) ....||1.7 x 10-2||9.3 x 10~4|
|Heat of combustion|
In the case of unsaturated compounds, cis- forms can become trans- forms, and vice versa; under the action of a small amount of iodine, hydrogen halides, or other reagent, the less stable (labile) form becomes the more stable form, but irradiation with ultraviolet light facilitates the reverse process. Geometric isomers also differ with respect to some chemical properties. Maleic acid, in which the carboxyl groups are spatially close, readily forms maleic anhydride:
whereas fumaric acid does not yield an anhydride.
Optical isomerism is characteristic of organic molecules that do not have a plane of symmetry (a plane dividing the molecule into two mirror images) and are not coincident with its mirror image (that is, with a molecule corresponding to the mirror image). Such asymmetrical molecules are optically active—they are capable of rotation of the plane of polarization of light when polarized light passes through a crystal, melt, or solution of the substance.
Crystals of some inorganic substances, such as quartz, are optically active, but in this case the activity results from asymmetry of the crystal lattice and disappears upon passage of the substance into other states of aggregation. The optical isomerism of organic substances depends only on molecular structure and is not associated with the state of aggregation. The Dutch chemist J. van’t Hoff (1874) was the first to propose an explanation of optical activity based on a tetrahedral model of the carbon atom.
Optical activity is most often caused by the presence in a molecule of an asymmetric carbon atom (a carbon atom bound to four different substituents). Lactic acid, CH3CH(OH)COOH (the asymmetric carbon atom is indicated by an asterisk), is an example. According to the tetrahedral model of the carbon atom, substituents are situated at the vertices of a regular tetrahedron, with the carbon atom at the center:
The above formulas show that no spatial rotation of the lactic acid molecule will make it coincide with its mirror image. The two forms of lactic acid are related in the same way as the right and left hands and are called optical antipodes (enantiomers).
Optical antipodes are identical in all physical and chemical properties except optical activity: one form rotates the plane of polarization of light to the left [the 1-form, or ( — )-form]; the other rotates it through the same angle but to the right [the d- form, or ( + )-form]. It is clear that the two forms of the same substance having opposite signs of rotation have mirror-opposed configurations. Identical sign of rotation for different substances does not prove identity of configuration, and substances with opposite signs of rotation can have the same configuration; this is exemplified by levorotatory lactic acid and its dextrorotatory esters.
The symbols L and D, which show the configurational relationship of a given active substance to the L- or D- glyceralde-hyde or to L- or D-glucose, respectively, are used to indicate the genetic link between substances. Levorotatory lactic acid is found to be related to the D- series and is therefore written as D-( —)-lactic acid; the dextrorotatory acid belongs to the L-series and is written as L-(+)-lactic acid.
A mixture of equal amounts of optical antipodes behaves like a separate chemical compound that is devoid of optical activity and differs greatly in physical properties from both of its constituents. Such a substance is called a racemic [the d,l- or (+) form]. In all chemical transformations in which new asymmetric carbon atoms are formed, racemics are always produced, since the probabilities of formation for the dextrorotatory and levorotatory forms are equal.
With compounds of the type abcC—C’’def, which have two asymmetric centers, four isomers are possible, depending on the configurations of the asymmetric atoms C and C”: levo-levo (I), levo-dextro (II), dextro-dextro (III), and dextro-levo (IV):
(where A and B are C’ and C” atoms, respectively).
Forms (I) and (III) and (II) and (IV) are optical antipodes, but forms (I) and (II), (I) and (IV), and (II) and (III) are not, because the configurations of one of their asymmetric centers are opposite, whereas those of the other are identical. Such optical isomers are called diastereoisomers, and they differ markedly with respect to all the most important physical properties. However, if all the substituents at the two asymmetric centers are the same —that is, with compounds of the type abc—C—C”—abc, such as the tartaric acids, HOOCCH(OH)CH(OH)COOH—forms (II) and (IV) will coincide, yielding an optically inactive form (the meso- form), since the optical activity of one center (C) is compensated by equal activity of opposite sign at the other center (C”).
Racemics can be resolved into optical antipodes; reaction with optically active compounds is generally used to achieve this.
Optical activity plays a major role in biological processes. Naturally occurring amino acids, carbohydrates, and alkaloids are optically active.
The optical activity of cyclic compounds is closely associated with geometric isomerism; thus, the trans- form of a disub-stituted cyclic compound, such as (XXXIII), does not coincide with its mirror image.
Chemical methods can be used to determine the relative configuration of a substance (whether it belongs to the D- or L-series). The actual problem of absolute configuration—that is, of the actual location of substituents around an asymmetric center—is solved by physical methods based on data of the dispersion of optical rotation and X-ray diffraction analysis. Optical isomerism may be due not only to the presence of asymmetric atoms but also to asymmetry of the molecule as a whole—as, for example, with substituted allenes and spirans:
In the case of diphenyl derivatives with bulky substituents in the ortho- positions, optical isomers can exist as a result of the difficulty of rotation of the benzene rings:
This particular form of isomerism is called atropoisomerism (it is essentially a special case of rotation isomerism).
Rotation isomerism. Rotation isomerism is caused by limited rotation of atoms or groups of atoms in a molecule around a C—C or other single bond. The geometric forms thus assumed by the molecule are called conformations, and the corresponding structures are called conformers (conformation or rotation isomers). The existence of preferred conformations is associated with the interaction among unbound atoms and groups of atoms. Theoretically a molecule can assume an infinite number of configurations, but usually only a few, energetically feasible ones are realized. For example, of all the possible conformations of ethane, the staggered conformation (a) is energetically most preferred, and the eclipsed conformation (b) is least preferred:
(the staggered conformation has minimum energy, and the eclipsed conformation has maximum energy; for most compounds the staggered conformations are the stable forms). The energy difference between forms (a) and (b) is 11.7 kilojoules per mole (kJ/mole), or 2.8 kilocalories per mole (kcal/mole), which is the energy barrier to rotation around the C—C bond in ethane —that is, the energy necessary for passage from a stable (staggered) conformation to the other conformation. Upon rotation of the CH3 groups through 360° with respect to one another, the ethane molecule assumes each of the conformations three times. In ethane all three stable conformations are identical. For substituted ethanes, such as 1,2-dichloroethane, they are not equivalent (two staggered and one eclipsed conformation are possible). Thus, the trans- conformation (c) is preferred over the skew, or gauche, conformation (d) by 5.02 kJ/mole (1.2 kcal/mole), and the actual difference between the trans- conformation (c) and the eclipsed conformation (e) is 20.93 kJ/mole (5 kcal/mole):
Except in the case of atropoisomerism mentioned above, the energy barriers of conformation transitions are not sufficiently high to make possible the isolation of rotation isomers, but they may be observed by such methods as infrared spectroscopy and nuclear magnetic resonance (often only at low temperatures). Research on the states of conformation is of great importance in studying the physicochemical properties and reactivity of substances.
REFERENCESEliel, E. Stereokhimiia soedinenii ugieroda. Moscow, 1965. (Translated from English.)
Terent’ev, A. P., and V.M. Potapov. Osnovy stereokhimii. Moscow-Leningrad, 1964.
B. L. DIATKIN