Conformational Analysis(redirected from Conformational isomerism)
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conformational analysis[kän·fər′mā·shən·əl ə′nal·ə·səs]
a branch of stereochemistry that studies the conformations of molecules and their relations to the physical and chemical properties of substances. The Dutch chemist J. H. Van’t Hoff based the stereochemical hypothesis he formulated (1874–75) on two principal postulates: (1) the valences of the saturated carbon atom are oriented in space toward the vertices of the tetrahedrons, and (2) the atoms or groups of atoms (substituents) in the molecule can freely rotate about single bonds without breaking them (unlike double bonds whose rigidity causes the formation of geometric isomers). Subsequently, the tetrahedral model of the carbon atom was confirmed by direct X-ray analysis. The supposition regarding the free rotation about single bonds was subjected to review, since it had been established that rotation about single bonds is not entirely “free”; during such rotation, energetically unequal geometric forms—conformations—or rotational isomers, some of which are energetically more favorable than others, emerge. Most of the molecules exist primarily in one or several stable (preferred) conformations. Energy barriers, which separate different conformations of the same substance, are usually equal to 20.9–62.7 kilojoules per mole (5–15 kilocalories per mole); individual conformations are constantly converting into one another. The investigations conducted by the British chemist D. Barton on the conformations in the cyclohexane series were of singular importance; Barton also introduced the term “conformational analysis” (1950).
In the paraffin hydrocarbon series, the necessity of conformational analysis is already evident in the case of ethane, which has two possible conformations: eclipsed (or even) and staggered (or odd). These are formed during the rotation of one methyl group with respect to another (Figure 1).
In an even ethane conformation, the hydrogen atoms are arranged closer together (“lined up behind one another”) and, consequently, the repulsion between them is stronger. Therefore the energy of the conformation is at a maximum (12.5 kilojoules per mole [3 kilocalories per mole] greater than the energy of the odd conformation). The molecule tends to pass from this energetically unfavorable state into one that is more stable (that is, into the odd conformation), with the hydrogen atoms arranged as far apart from one another as possible. In this more favorable position, rotation about the C—C bond is somewhat hindered.
Substituents with a greater bulk than hydrogen cannot occupy the even (eclipsed) positions. Therefore, as in the case of butane, CH4—CH2—CH2—CH3, only three odd conformations should be examined (Figure 2), the most favorable being the trans conformation. The number of possible conformations that the molecule can assume increases rapidly with an increase in the length of the carbon chain and the emergence of substituents. In general, the most favorable conformations are those in which the bulky substituents are arranged at maximum distances from one another (as in the trans conformation of butane). However, if an electrostatic attraction or hydrogen bond should occur between the substituents, then the skew, or gauche, conformation may
prove to be more convenient, for example, as in ethylene chlorhydrine, HOCH2—CH2C1 (Figure 3).
The nature of chemical transformations in a substance frequently depends on the conformation of its molecules. For example, the debromination of 2,3-dibromobutane with metallic zinc is possible only in a trans position of the reacting bromine atoms. Therefore, two diastereomers of 2,3-dibromobutane yield geometrically isomeric olefins (Figure 4).
Conformational representations are highly important in explaining the properties of cyclic compounds, especially in the series derived from cyclohexane. The last primarily occurs in the chair form, which is particularly favorable since the valency angles are not distorted and the conformations along all the C—C bonds are odd (Figure 5). The remaining two valence bonds of each ring carbon atom are either oriented perpendicularly to the ring (axial bonds—a) or are directed along its periphery (equatorial bonds—e). The equatorial distribution of substituents is more favorable. For example, at room temperature, the conformational equilibrium of chlorocyclohexane e:a = 70:30. When the temperature is lowered to - 150°C, the interconversion rate is sharply reduced; under these conditions it is possible to isolate the pure e-form of chlorocyclohexane. A conformational analysis of the cyclohexane ring enables one, for example, to understand the reason why both cis- and trans- cyclohexane-1,2-dicarboxylic acid can form an anhydride (in both cases the dihedral angle between the bonds leading to the COOH groups is 60°).
In addition to chemical methods, physical methods are also widely used in conformational analysis, particularly the nuclear magnetic resonance method. The data obtained on the conformations of organic compounds serve as an important basis for the interpretation and prediction of the properties of the compounds. Conformational representations have assumed great importance in the chemistry of synthetic and natural macromolecular compounds, as well as in the field of physiologically active substances.
REFERENCESKonformatsionnyi analiz. Moscow, 1969. (Translated from English.)
Eliel, E. Osnovy stereokhimii. Moscow, 1971. (Translated from English.)
Terent’ev, A. P., and V. M. Potapov. Osnovy stereokhimii. Moscow-Leningrad, 1964.
V. M. POTAPOV