Conformational analysis

(kän·fər′mā·shən·əl ə′nal·ə·səs)

(physical chemistry) The determination of the arrangement in space of the constituent atoms of a molecule that may rotate about a single bond.

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The study of the energies and structures of conformations of organic molecules and their chemical and physical properties. Organic molecules are not static entities. The constituent atoms vibrate and groups rotate about the bond axes. See also Stereochemistry.

Linear structures

Rotation about the C-C bond in ethane, for example, results in an infinite number of slightly different structures called conformations; one of these is indicated below. In conformation (1) of ethane, the pairs of C-H bonds on the 1

two carbon atoms reside in a plane, and are termed eclipsed. (The circle represents the front-most carbon atom, and the long bonds those from that carbon atom to the hydrogen atoms. The bonds from the circle represent those bonds from the rearward carbon to its hydrogen atoms.) Conformation (1) is called the eclipsed conformation. In conformation (2), the C-H bonds on one carbon reside between the C-H bonds on the other carbon. Conformation (2) is called the staggered conformation. An infinite number of conformations between (1) and (2) are possible; however, conformations (1) and (2) are of greatest interest because they are the maximum and minimum energy structures. In conformation (1), the electrons in the C-H bonds and the nuclear charges of the hydrogen atoms repel each other, resulting in a higher energy state. In conformation (2), the electrons and hydrogen atoms are at their greatest possible separation and the repulsion is at a minimum. The conversion of (2) to (3) by rotation of one of the methyl groups by 120° requires the input of energy, approximately 3.0 kcal (13 kilojoules) per mole, in order to pass through the eclipsed conformation. This amount is small compared to the thermal energy at room temperature, and the rotation about the C-C bond in ethane occurs at about 10⁹–10¹⁰ times per second. 2

Butane provides a more complicated case. There are two different eclipsed (4 and 6) and two staggered (5 and 7) 4

5 6 7 conformations which are designated by the names below the structures. As the methyl group is larger than a hydrogen atom, (4) is higher in energy than (6), and (5) is higher in energy than (7). As the molecular weight of an alkane increases, the number of molecular conformations (combinations of all possible individual bond conformations) increases dramatically, although the antiperiplanar conformations are always favored.

Cyclic structures

These also exist in various conformations. Cyclopropane, a planar structure, can exist in only one conformation. In cyclobutane, slight twisting about the C-C bonds can occur which relieves some of the C-H eclipsing strain energy. Cyclobutane exists in rapidly interconverting so-called butterfly conformations (8). Cyclopentane exists in two types of 8

nonplanar conformations: the envelope conformation (9) and the half-chair (or twist) conformation (10). The flap atom of (9), 9 10 the atom out of the plane of the other four, can migrate around the ring, as can also the twist in (10). These motions, called pseudorotation, require very little energy, and cyclopentane presents a very complex conformational system.

Cyclohexane exists predominantly in the chair conformation (11), in which all C-C bond conformations are of the staggered type. Interconversion between chair conformations occurs rapidly at room temperature, passing through the high-energy, boat conformation (12). In the chair conformation, there are two 11

distinctly different types of hydrogen atoms; one set oriented perpendicular to the general plane of the ring, called axial (a) hydrogens, and one set oriented parallel to the plane of the ring, called equatorial (e) hydrogens. These hydrogens interchange orientation on chair interconversion. Axial and equatorial hydrogens possess different chemical and physical properties, although at room temperature the interconversion occurs very rapidly (∼10⁵ per second), and it is in general not possible to detect the differences. It is easy to design molecules in which the interconversion is not possible and the differences in properties become readily apparent.

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