Lectures 2 and 3: Structure and Conformation

Principal topics: Conformational analysis of acyclic hydrocarbons; molecular mechanics and strain; types and classification of ring systems; structure and strain in saturated ring compounds; cyclohexane; axial and equatorial substitutents on cyclohexane rings; some medium and large ring structures; polycyclic structures; bicyclic analogues of cyclohexane; macro(bi)cyclic compounds and host/guest chemistry.

Conformational analysis of acyclic hydrocarbons (V&S 64-72, CGWW 450)

Revision of butane conformations. Energy cost of a single g-butane interaction is about 0.9 kcal/mol, and this provides a useful yardstick for assessing other torsional interactions.

Entropy often favours gauche conformations, because they come in pairs At RT, only 50% of n-hexane molecules would be in the all-anti conformation.

Molecular mechanics and strain

The factorisation of strain energy is the basis of molecular mechanics and this also supplies the right framework to think about strain (C&S A118):-

You should have some knowledge of standard bond lengths (C&S A12), and bond angles (and know how these depend on hybridisation).

Torsion angles (also known as dihedral angles) determine conformation.

Steric effects (M 274) include non-bonding effects, strain, and steric inhibition of conjugation.

Types and Classification of Ring Systems

Monocyclic, bicyclic,...polycyclic

Carbocyclic

Heterocyclic

Alicyclic
(non-aromatic)
discussed here

Aromatic
(see Professor Simpson's Level 2 lectures)

Non-aromatic
discussed here

Heteroaromatic
(see Dr Hart's Level 2 lectures)

Classification by ring size:-

Type of Ring

Number of Ring Atoms

Strain Energy

Types of strain

Small

3-4

High

Ebend,Etorsion

Common

5, 6, (7)

Low

 

Medium

(7), 8-11

Fairly high

Evan der Waals,Etorsion, Ebend

Large
(macrocycles)

12 and over

Low

 

Structure and strain in saturated ring compounds.

The emphasis will be on hydrocarbons, but most points apply to heterocyclic analogues as well (i.e. THF is like cyclopentane).

From the heats of combustion of saturated straight-chain hydrocarbons, an increment of -157.4 kcal/mol per CH2 group can be calculated. Therefore the heat of combustion of a strain-free cyclic hydrocarbon (CH2)n should be -157.4 x n kcal/mol. Experimental heats of combustion are higher that this and the difference is the strain energy (V&S Table 4.2, p.133, CGWW 454).

Revision! Three- to Five- Membered Rings (V&S 134-136, CGWW 456) I will not talk about these in lectures but you must know about them.

Cyclopropane is flat (of course!), so there is not only severe angle strain, but all the bonds are also eclipsed. The bond angle (60o) is smaller that the angle between any orbitals on the carbon atoms (minimum 90o for two pure p orbitals), so the bonds are bent (weak), and carbon uses more p character in the hybrid orbitals making these bonds.

If cyclobutane were flat, all bonds would be eclipsed, so it folds to about 25o; this causes some decrease of bond angles - the structure (like many others) is a compromise.

Cyclopentane is not flat (because of eclipsing!), but rapidly pseudorotating (wriggling) between non-planar forms - envelope and twist (V&S misleadingly call the latter "half-chair").

Cyclohexane (V&S 136-145, CGWW 457)

The chair form of cyclohexane is perfect and is closely related to the diamond lattice.

Learn to draw it if you havenít done so already! (see V&S 140, CGWW 459)

The twist form (also known as twist boat and skew boat) isn't very clearly drawn in V&S. It has three axes of symmetry Ė make a model and see if you can find them!

Cyclohexane shows one sharp line in 1H NMR at room temperature, but this broadens as the temperature is lowered, and the spectrum below -60 ° C is complex with two chemical shifts, d eq and d ax, and four coupling constants, Jgem, Jeq,eq, Jeq,ax, and Jax,ax. From the VT behaviour of the spectrum, the activation energy for chair-to-chair interconversion via the twist form can be found (V&S 139-141). It is actually easier to do this from the spectra of C6H11D or 1,1-difluorocyclohexane. Using other data from calculations, the following picture of the interconversion pathway can be obtained. The transition state preserves an axis of symmetry.

Axial and Equatorial Substitutents on Cyclohexane Rings (V&S 142-5, CGWW 462).

The first rule is that all substituents prefer to go equatorial whenever possible.

If one of the substitutents must go axial for the ring to stay in a chair form, this is usually preferred to forcing the ring into a twist form; but But is an exception.

Conformational free energy differences between having substituents axial or equatorial are known as A values (V&S 143, Table 4-3). A values are normally roughly additive. However this is not true when two groups come close in a 1,3-diaxial interaction (energy cost about 10 kJ/mol); so the conformation of cis-1,3-dimethylcyclohexane shown below is very unfavourable.

The A value for an OH group varies with solvent due to hydrogen bonding (0.52 in non-hydrogen bonding solvents; 0.87 in hydrogen bonding solvents). Hydrogen-bonding may stabilise a 1,3 diaxial form e.g. in 1,3-dihydroxycyclohexane. Lone pairs are smaller than hydrogen; e.g. piperidine has its N-H equatorial.

A values are also not additive when strongly polar groups are involved, e.g. in 2-chlorocyclohexanone and related compounds the axial conformer has less dipole repulsion and is the more stable form (C &S A139). In these cases too, the conformational equilibrium may be solvent-dependent. See also the anomeric effect discussed in lectures 5-6.

Some Medium and Large Ring Structures (C & S A142-4)

Cycloheptane: the chair form has an eclipsed bond and goes to twist chair which is the most stable.

In general, all larger odd-membered rings are complicated, with many possible conformations of similar energy.

Cyclooctane: three basic conformations, BB (diamond lattice, but bad H...H interactions), BC (best), CC or crown (bad torsional angles). All have a trade-off between torsional and non-bonded strain.

Cyclodecane: the BCB form is best and comes from the diamond lattice, but it does have bad transannular interactions between some hydrogen atoms.

18-Crown-6 has a diamond lattice structure when complexed to a potassium ion (C&S A237-8).

Bi- and Poly-cyclic structures

There are three basic ways in which two rings can be joined:-

 

Spiran

Fused

Bridged

No. of atoms common to both rings

1

2

3 or more

Example

Name

Spiro[5.5]undecane

trans-Bicyclo[4.4.0]decane

Bicyclo[3.3.1]nonane

Bicyclic fused and bridged ring systems are named by counting round the bridges between the bridgehead atoms, and listing these in order, with the largest bridge first. Atoms are numbered in the same order, starting at one of the bridgeheads. (N.B. the numbers in the square brackets must add up to two less than the total in the suffix).

Bicyclic Analogues of Cyclohexane

Bicyclo[4.4.0]decane (also called decalin or decahydronaphthalene) has cis- and trans-forms (V&S 146, CGWW 465). The cis-isomer can interconvert between two double-chair forms (which are enantiomers). However, the trans-isomer only has one possible double-chair form. Substitutents may be therefore be forced to be axial.

A few representative poly-cyclic compounds

Propellanes have one bond shared between three rings (C&S A6-7, M134). [1.1.1]Propellane has all C-C bonds to bridgehead carbon in one hemisphere. The central bond is most unusual; there appears to be no excess electron density in it!

Dodecahedrane has very little angle strain but note that all bonds are completely eclipsed, so itís by no means strain-free.

Adamantane has a diamond lattice structure and is the most stable C10H16 hydrocarbon. It is formed by acid-catalysed rearrangement of other C10H16 compounds.

Cryptands are examples of macrobicyclic compounds - they form complexes with metal ions called cryptates. They can also show a novel type of isomerisism: in- and out-bridgeheads. Even larger structures are required to act as host and encapsulate other molecules.

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