Isomers, conformational

Conformational isomers conformers) are different shapes of the same molecule resulting from rotation around a single bond, such as C—C. They are not different compounds (i.e. they have the same physical and chemical properties) and are readily interconvertable (Section 3.2). 

Configurational isomers have the same molecular formula and, although the atoms are joined together in the same way, they are arranged differently in space (with respect to each other). They are not readily interconvertable (Section 3.3). 

The different arrangements of atoms caused by rotation about a single bond are called conformations. A conformational isomer, or conformer, is a compound with a particular conformation. Conformational isomers can be represented by Sawhorse projections or Newman projections. 

Rotation about the C C bond produces two distinctive conformations. 

Staggered conformation - C—H bonds on each carbon atom are as far apart as possible. 

Stereoisomers, on the other hand, are compounds with the same molecular formula, and the same sequence of covalently bonded atoms, but with a different spatial orientation. Two major classes of stereoisomers are recognized, conformational isomers and configurational isomers. 

Conformational isomers, or conformers, interconvert easily by rotation about single bonds. Configurational isomers interconvert only with difficulty and, if they do, usually require bond breaking. We shall study these in turn. 

The staggered conformation is more stable as the C-H bonds are further apart. The energy difference between them (12kJmol 1) is known as the torsional strain. This energy difference is relatively small, and hence there is free rotation about the C-C bond at room temperature. 

S = staggered conformer E = eclipsed conformer T = torsional energy 

The angle between the C-H bonds on the front and back carbon is known as the dihedral (or torsional) angle. 

Exercise 5-4 How many chiral centers are evident in the structure of cholesterol Identify them by the number of the carbon atom. 

Exercise 5-5 The work of the German chemist Wislicenus on hydroxypropanoic acids was influential in the development of van t Hoff s ideas on stereoisomerism. By 1869, Wislicenus had established that there are three isomeric hydroxypropanoic acids, let us call them A, B, and C, of partial structure CzH4(OH)(C02H). Isomer A was isolated from sour milk and Isomer B from a meat extract. Both A and B had the same physical properties, except for optical rotation, wherein A was levorotatory and B was dextrorotatory. Isomer C was not optically active and had considerably different physical and chemical properties from A or B. Work out structures A, B, and C in as much detail as you can from the information given. 

Exercise 5-6 Examine the structures of /3-carotene and vitamin A shown on p. 33 and p. 50 and determine the configuration at each of the double bonds in the chain attached to the ring(s). Are these substances chiral or achiral  

For ethane and its derivatives, the staggered conformations are more stable than the eclipsed conformations. The reason for this in ethane is not 

4This is by no means a trivial amount of energy-the difference in energy between the staggered and eclipsed forms of 1 mole (30 g) of ethane being enough to heat 30 g of water from 0° to 100°. 

A study of the various stable conformations of the guanidine group in cimetidine led to a rethink of the type of bonding which might be taking place at the antagonist site. Up until this point, the favoured theory had been a bidentate hydrogen interaction as shown in Fig. 13.17. 

In order to achieve this kind of bonding, the guanidine group in cimetidine would have to adopt the Z,Z conformation shown in Fig. 13.42. 

Further support for this theory is provided by the weak activity observed for the urea analogue (Fig. 13.32). This compound is known to prefer the Z,Z conformation over the Z,E or E,Z and would therefore be unable to bind to both hydrogen bonding sites. 

For example, the nitropyrrole derivative (Fig. 13.44) has been shown to be the strongest antagonist in the cimetidine series, implying that the E,Z conformation is the active conformation. 

The isocytosine ring (Fig. 13.45) has also been used to lock the guanidine group, limiting the number of conformations available. The ring allows further substitution and development as seen below (Section 13.12.2.). 

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Conformational Isomers. A molecule in a conformation into which its atoms return spontaneously after small displacements is termed a conformer. Different arrangements of atoms that can be converted into one another by rotation about single bonds are called conformational isomers (see Fig. 1.1). A pair of conformational isomers can be but do not have to be mirror images of each other. When they are not mirror images, they are called diastereomers. 

When two different substituents are attached to each carbon atom of the double bond, cis-trans isomers can exist. In the case of c T-2-butene (Fig. 1.11a), both methyl groups are on the same side of the double bond. The other isomer has the methyl groups on opposite sides and is designated as rran5--2-butene (Fig. l.llb). Their physical properties are quite different. Geometric isomerism can also exist in ring systems examples were cited in the previous discussion on conformational isomers. 

The results are critically dependent on the level of theory. However, a stepwise mechanism with closed shell structures along the reaction path was found to be lower in energy than a concerted reaction. An all-cw conformer of 172 is reported to be a transition state rather than an intermediate. Similarities of the conformational isomers of the intermediate 2-butenedithial 172 with the dinitrosoethylenes discussed in Section IV,c are evident. 3,6-Diamino-substituted dithiins are predicted to be more stable in the open-chain bisthioamide structure [95JST51]. The... 

The different arrangements of atoms that result from bond rotation are called conformations, and molecules that have different arrangements are called conformational isomers, or conformers. Unlike constitutional isomers, however, different conformers can t usually be isolated because they interconvert too rapidly. 

Conformational isomers are represented in two ways, as shown in Figure 3.6. A sawhorse representation views the carbon-carbon bond from an oblique angle and indicates spatial orientation by showing all C-Tl bonds. A Newman projection views the carbon-carbon bond directly end-on and represents the two carbon atoms by a circle. Bonds attached to the front carbon are represented by lines to the center of the circle, and bonds attached to the rear carbon are represented by lines to the edge of the circle. 

The molecular formulas of PMs (Table 9.5) obtained by high-resolution mass spectrometry in collaboration with Prof. Y. Kishi, Harvard University, indicate that PMs are formed by the condensation of three molecules of PS and two molecules of methylamine, with the removal of four water molecules. No study has been made on their conformational isomers. 

Li" " and Na+ (preferentially Na" ), but not K", Mg or Ca. Molecules such as these, whose cavities can be occupied only by spherical entities, have been called spherands. Other types are calixarenes (e.g., 22). There is significant hydrogen bonding involving the phenolic OH units in [4]calixarenes, but this diminishes as the size of the cavity increases in larger ring calixarenes. There are also calix[4]-arenes, which have been shown to have conformational isomers (see p. 167) in... 

If two different three-dimensional arrangements in space of the atoms in a molecule are interconvertible merely by free rotation about bonds, they are called conformationsIf they are not interconvertible, they are called configurations Configurations represent isomers that can be separated, as previously discussed in this chapter. Conformations represent conformers, which are rapidly interconvertible and are thus nonseparable. The terms conformational isomer and rotamer are sometimes used instead of conformer . A number of methods have been used to determine conformations. These include X-ray and electron diffraction, IR, Raman, UV, NMR, and microwave spectra, photoelectron spectroscopy, supersonic molecular jet spectroscopy, and optical rotatory dispersion (ORD) and CD measurements. Some of these methods are useful only for solids. It must be kept in mind that the conformation of a molecule in the solid state is not necessarily the same as in solution. Conformations can be calculated by a method called molecular mechanics (p. 178). 

Table 4 Geometrical parameters of two bond lengths data from ref [17]) conformational isomers of gaseous trisulfane (r ...

Fig. 2 Three conformational isomers of the tetrasulfane molecule H2S4 differing by the signs of the torsional angles at the three SS bonds (after [47])...

A peptoid pentamer of five poro-substituted (S)-N-(l-phenylethyl)glycine monomers, which exhibits the characteristic a-helix-like CD spectrum described above, was further analyzed by 2D-NMR [42]. Although this pentamer has a dynamic structure and adopts a family of conformations in methanol solution, 50-60% of the population exists as a right-handed helical conformer, containing all cis-amide bonds (in agreement with modeling studies [3]), with about three residues per turn and a pitch of 6 A. Minor families of conformational isomers arise from cis/trans-amide bond isomerization. Since many peptoid sequences with chiral aromatic side chains share similar CD characteristics with this helical pentamer, the type of CD spectrum described above can be considered to be indicative of the formation of this class of peptoid helix in general. 

Figure 2.25. Energy landscape (BP/DNP) for the Cu ZSM-5 + 2NO- Cu—0 ZSM-5 + N20 reaction, showing all associated spin and conformation isomers calculated for the M5 site. The values are given in kcal x mol-1. The letters S, D and T indicate the singlet, doublet, and triplet states, respectively (after [75]).

Chirality transfer in catalytic asymmetric hydrogenation can be achieved not only by using powerful chiral ligands such as BINAP or DuPhos but also by the formation of a dynamic conformational isomer. The availability of many enantiomerically pure diols allows the production of electron-deficient, bi-dentate phosphate in the form of 27. The backbone O-R -O can define the chirality of the 0-R2-0 in complex 28, hence realizing the chirality transfer.44... 

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