CHEM 0310 Ch 4

The activation barrier separating the most stable chair from the boat forms is

10.8 kcal/mol

Constitutional (or structural) isomers

Constitutional (or structural) isomers are compounds that have the same molecular formula and different connectivity.

Naming a substituted cyclic alkane

In monosubstituted systems, the carbon of attachment is defined as carbon 1 of the ring. For polysubstituted compounds, provide the lowest possible numbering sequence. When two such sequences are possible, the alphabetical order of the substituent names takes precedence.

Disubstituted cycloalkanes can be stereoisomers

In one isomer, the two substituents are positioned on the same face (side) of the ring. Substituents on the same face are called cis. In the other isomer, they are on opposite faces. Substituents on opposite faces are called trans.

equatorial conformer of methylcyclohexane

In the equatorial conformer, the methyl group extends into space away from the remainder of the molecule.

Calculating A-values: Example 7

In this example, the gauche interactions "cancel" out.

ring-fusion carbons

shared carbon atoms

ΔH°comb pattern

ΔH°comb increases by about the same amount with each successive member of the homologous series (about 157 kcal/mol for each additional CH2 moiety).

cycloalkyl radicals

Radicals derived from cycloalkanes by abstraction of a hydrogen atom Substituted cycloalkanes are sometimes named as cycloalkyl derivatives. The smaller unit is treated as a substituent to the larger one. For example, methylcyclopropane (not cyclopropylmethane) and cyclobutylcyclohexane (not cyclohexylclycobutane).

When we measure the actual heats of combustion of these molecules, they turn out to be generally larger in magnitude. What causes this extra energy?

Ring strain

Why is cyclohexane so important?

The cyclohexane ring is one of the most common and important structural units in organic chemistry. Its substituted derivatives exist in many natural products, and an understanding of its conformational mobility is an important aspect of organic chemistry.

Cyclopropane has C - C - C bond angles of 60°, a significant deviation from the "natural" tetrahedral bond angle of 109.5°. How is it possible for three supposedly tetrahedral carbon atoms to maintain a bonding relation at such highly distorted angles?

The figure illustrates the bonding in the strain-free "open cyclopropane," the trimethylene diradical •CH2 CH2 CH2• compared with that in the closed form. The two ends of the trimethylene diradical cannot "reach" far enough to close the ring without "bending" the two C - C bonds already present. However, if all three C - C bonds in adopt a bent configuration (interorbital angle of 104), overlap is sufficient for bond formation. The energy needed to distort the tetrahedral carbons enough to close the ring is called bond-angle strain. The ring strain in cyclopropane is derived from a combination of eclipsing and bond-angle contributions. As a consequence of its structure, cyclopropane has relatively weak C - C bonds [DH° = 65 kcal/mol]. This value is low because breaking the bond opens the ring and relieves ring strain.

is ring structure important?

The majority of organic compounds occurring in nature contain rings. So many fundamental biological functions depend on the chemistry of ring-containing compounds that life as we know it could not exist in their absence.

axial conformer of methylcyclohexane

The methyl substituent is close to the other two axial hydrogens on the same side of the molecule. The distance to these hydrogens is small enough (about 2.7 Å) to result in steric repulsion, another example of transannular strain. Because this effect is due to axial substituents on carbon atoms that have a 1,3-relation (in the drawing, 1,3 and 1,3'), it is called a 1,3-diaxial interaction. This interaction is the same as that resulting in the gauche conformation of butane. Thus, the axial methyl group is gauche to two of the ring carbons (C3 and C3'); when it is in the equatorial position, it is anti to the same nuclei.

ΔH°comb of the cycloalkanes

With this requisite value for ΔH°comb(CH2), we can calculate the expected ΔH°comb of the cycloalkanes (CH2)n -(n x 157.4) kcal/mol

Why is cyclohexane unique?

Within experimental error, cyclohexane is unusual in that it is free of bond-angle or eclipsing strain.

A hypothetical planar cyclohexane

Would suffer from 12 H - H eclipsing interactions and sixfold bond-angle strain (a regular hexagon requires 120° bond angles)

Several enthalpic factors control the stabilities of cyclic molecules

1) deviations from the ideal bond angle of 109.5° for sp3-hybridized carbons 2) forcing atoms into eclipsing orientations 3) making electrons lie off of the internuclear axis 4) enforced remote steric interactions ALL OF THESE ARE DE-STABILIZING

There are two puckered conformations possible for cyclopentane

1) the envelope 2) the half chair There is little difference in energy between them, and the activation barriers for rapid interconversion are extremely low, averaging the positions of all carbons and hydrogens.

Calculating A-values: Example 4

1,2-diequatorial cyclohexanes have a gauche interaction that makes their energy slightly higher than what would be expected. The gauche interaction causes an energetic penalty.

Calculating A-values: Example 5

1,3-diaxial cyclohexanes have a transannular (syn-pentane) interaction that makes their energy higher than what would be expected.

Calculating A-values: Example 6

1,4-interactions can be treated as the sum of the A-values for the substituents. There's no gauche interactions (substituents are far apart). There's no diaxial interactions (substituents are on opposite ends).

Because of these trends, organic chemists have loosely defined four groups of cycloalkanes:

1. Small rings (cyclopropane, cyclobutane) 2. Common rings (cyclopentane, cyclohexane, cycloheptane) 3. Medium rings (from 8- to 12-membered) 4. Large rings (13-membered and larger)

Delta H comb Pattern

A similar calculation for cyclobutane reveals a ring strain of 26.3 kcal/mol (6.6 kcal/mol per CH2 group). In cyclopentane, this effect is much smaller, with the total strain amounting to only 6.5 kcal/mol. Cyclohexane is virtually strain free. Succeeding members of the series again show considerable strain until we reach very large rings.

Naming cycloalkanes

Alkane names are preceded by the prefix cyclo-.

Torsional strain in cyclopropane

All methylene hydrogens are eclipsed, much like the hydrogens in the eclipsed conformation of ethane. The energy of the eclipsed form of ethane is higher than that of the more stable staggered conformation because of eclipsing (torsional) strain. This effect is also present in cyclopropane.

As ring size increases, strain _________

As ring size increases, strain diminishes; cyclohexane can be assembled without distortion or strain.

Calculating A-values: Example 3

B is favored.

cyclohexane is as inert as a straight-chain alkane

Because of its lack of strain

Intermediate form - Twist-boat (Skew-boat) form

Boat cyclohexane is fairly flexible. If one of the C - C bonds is twisted relative to another, this form can be somewhat stabilized by partial removal of the transannular interaction. The new conformation obtained is the twist-boat (skew-boat. The stabilization relative to the boat form amounts to about 1.4 kcal/mol. Two twist-boat forms are possible. They interconvert rapidly, with the boat conformer acting as a transition state.

Cyclobutane - characteristics

Bond-angle strain is considerably reduced relative to that in cyclopropane, although maximum overlap is, again, only possible with the use of bent bonds. The C - C bond strength in cyclobutane also is low (about 63 kcal/mol) because of the release of ring strain on ring opening and the consequences of relatively poor overlap in bent bonds. Cyclobutane is less reactive than cyclopropane but undergoes similar ring-opening processes.

Bridged bicylic molecules

Bridged bicylic molecules have two rings that share 2 nonconsecutive atoms.

ΔH comb of cyclohexane (predicted, actual)

Calculated ΔHcomb (-944.4 kcal/mol) based on a strain-free (CH2)6 model Experimentally determined value (-944.5 kcal/mol) Indeed, the C--C bond strength, DH = 88 kcal/mol is normal

Intermediate form - Boat form

Carbons 1 and 4 are out of the plane in the same direction Less stable than the chair form by 6.9 kcal/mol One reason for this difference is the eclipsing of eight hydrogen atoms at the base of the boat. Another is steric hindrance due to the close proximity of the two inside hydrogens in the boat framework. T he distance between these two hydrogens is only 1.83 Å, small enough to create an energy of repulsion of about 3 kcal/mol. This effect is an example of transannular strain, which is described as strain resulting from steric crowding of two groups across a ring.

Why are cis and trans isomers not conformational isomers?

Cis and trans isomers can be interconverted only by breaking bonds.

Cycloalkanes formula

CnH2n

The properties of the cycloalkanes differ from those of their straight-chain analogs

Compared with the corresponding straight-chain alkanes, the cycloalkanes have higher boiling and melting points as well as higher densities. These differences are due in large part to increased London interactions of the relatively more rigid and more symmetric cyclic systems. In comparing lower cycloalkanes possessing an odd number of carbons with those having an even number, we find a pronounced alternation in their melting points. This phenomenon has been ascribed to differences in crystal packing forces between the two series.

What is the benefit of the chair conformation?

Completely eliminates ring strain by allowing all bond angles to be 109.5° and by placing all peripheral substituents in staggered conformations Eclipsing is completely absent, and the bond angles are very nearly tetrahedral

Larger cycloalkanes

Cyclolkanes with rings larger than that of cyclohexane also have more strain. This strain is due to a combination of bond-angle distortion, partial eclipsing of hydrogens, and transannular steric repulsions. It is not possible for medium-sized rings to relieve all of these strain-producing interactions in a single conformation. Instead, a compromise solution is found in which the molecule equilibrates among several geometries that are very close in energy. One such conformation of cyclodecane, which has a strain energy of 14 kcal/mol, is shown. Essentially strain-free conformations are attainable only for large-sized cycloalkanes, such as cyclotetradecane. In such rings, the carbon chain adopts a structure very similar to that of the straight-chain alkanes, having staggered hydrogens and an all-anti configuration. However, even in these systems, the attachment of substituents usually introduces various amounts of strain. Most cyclic molecules described in this book are not strain free.

Cyclopentane - Summary

Cyclopentane has relatively little ring strain, and its C--C bond strength (DHo = 81 kcal/mol) approaches that in acyclic alkanes. As a consequence, it doesn't show the unusual reactivity of three- or four-membered rings.

Cyclopentane strain

Cyclopentane might be expected to be planar because the angles in a regular pentagon are 108°, close to tetrahedral. However, such a planar arrangement would have ten H - H eclipsing interactions. Cyclopentane adapts an envelope-type conformation that nearly, but not completely, eliminates torsional strain

the first 3 cycloalkanes

Cyclopropane Cyclobutane Cyclohexane

In what other way does cyclopropane accomodate the strain?

Cyclopropane also accommodates the unusual bond angle by placing higher p-character in the orbitals that form the carbon-carbon bonds, meaning that the orbitals that contain the carbon-hydrogen bonds contain higher s-character. One consequence of this hybridization is that cyclopropane C-H bonds are stronger than C-H bonds in acyclic alkanes

Diosgenin - an example of a naturally occurring steroid

Diosgenin is obtained from root extracts of the Mexican yam and used as a starting material for the synthesis of several commercial steroids. Most striking is the number of rings in the compound.

Because of the possibility of structural and cis-trans isomerism, a variety of structural possibilities exist in substituted cycloalkanes

For example, there are eight isomeric bromomethylcyclohexanes (three are shown below), all with different and distinct physical and chemical properties.

Fused bicylcic molecules

Fused bicylcic molecules have two rings that share 2 consecutive atoms.

ring-fusion substituents

Groups attached to ring-fusion carbons

cyclic alkanes (or carbocycles or cycloalkanes)

Hydrocarbons containing single-bonded carbon atoms arranged in rings

1,1-dimethylcyclohexane

In 1,1-dimethylcyclohexane, one methyl group is always equatorial and the other axial. The two chair forms are identical, and hence their energies are equal.

The energy differences between the axial and the equatorial forms of many monosubstituted cyclohexanes have been measured.

In many cases, particularly for alkyl substituents, the energy difference between the two forms increases with the size of the substituent, a direct consequence of increasing unfavorable 1,3-diaxial interactions. This effect is particularly pronounced in (1,1-dimethylethyl)cyclohexane (tert-butylcyclohexane). The energy difference here is so large (about 5 kcal/mol) that very little (about 0.01%) of the axial conformer is present at equilibrium.

trans-1,4-dimethylcyclohexane

On the other hand, the trans isomer can exist in two different chair conformations: one having two axial methyl groups (diaxial) and the other having two equatorial groups (diequatorial).

The chair conformation of cyclohexane

One conformation of cyclohexane, obtained by moving carbons 1 and 4 out of planarity in opposite directions is strain free

What is the value of measuring heat of combustion?

One measure of the stability of a molecule is its heat content. The heat content of an alkane can be estimated by measuring its heat of combustion. The heats of combustion of the cycloalkanes reveal the presence of ring strain.

Cyclobutane

Planar cyclobutane would have even greater torsional strain that cyclopropane because of the greater number of eclipsing interactions. Cyclobutane can pucker to partially alleviate torsional strain, but bond angle strain is still significant. The structure of cyclobutane reveals that this molecule is not planar but puckered, with an approximate bending angle of 26°. The nonplanar structure of the ring, however, is not very rigid. The molecule "flips" rapidly from one puckered conformation to the other. Puckered cyclobutane is a highly dynamic (fluxional) molecule, with a barrier between puckered forms of about 1.5 kcal/mol. Distorting the four-membered ring from planarity is favorable: It partly relieves the strain introduced by the eight eclipsing hydrogens.

cis-1,4-dimethylcyclohexane

Similarly, in cis-1,4-dimethylcyclohexane, both chairs have one axial and one equatorial substituent and are of equal energy.

The chair-conformation model of cyclohexane reveals that the molecule has two types of hydrogens.

Six carbon - hydrogen bonds are nearly parallel to the principal molecular axis and hence are referred to as axial; the other six are nearly perpendicular to the axis and close to the equatorial plane and are therefore called equatorial. Axial substituents have gauche relationships with the ring while equatorial substituents have anti relationships with the ring. Axial substituents have tranaxial (across a ring) steric interactions with other axial substituents while equatorial substituents do not.

Common errors when drawing the chair conformation

Starting with the chair structure on the left, you simply "flip" the CH2 group farthest to the left (C1 in the preceding section) upward through the equatorial plane to generate the boat conformers. If you now return the molecule to the chair form not by a reversal of the movement but by the equally probable alternative — namely, the flipping downward of the opposite CH2 group (C4) — the original sets of axial and equatorial positions have traded places. In other words, cyclohexane undergoes chair - chair interconversions ("flipping") in which all axial hydrogens in one chair become equatorial in the other and vice versa. The activation energy for this process is 10.8 kcal/mol. This value is so low that, at room temperature, the two chair forms interconvert rapidly (approximately 200,000 times per second).

Stereoisomers

Stereoisomers are isomeric molecules that have the same molecular formula and sequence of bonded atoms (constitution), but differ in the three-dimensional orientations of their atoms in space.

Both bond angle strain and torsional strain contribute to the overall strain found in cyclopropane.

The carbon skeleton in cyclopropane is by necessity flat and quite rigid, and bond rotation that might relieve eclipsing strain is very difficult.

ring strain

The reason for ring strain lies in the tetrahedral carbon model. The C - C - C bond angles in cyclopropane (60°) and cyclobutane (90°) differ considerably from the tetrahedral value of 109.5°.

Bond angle strain in cyclopropane

The strain per CH2 group in this molecule is 9.2 kcal/mol.

Chair-Chair Interconversion

The two chair forms shown above are, except for the color coding, identical. We can lift this degeneracy by introducing substituents: Now the chair with a substituent in the equatorial position is different from its conformer, in which the substituent is axial. The preference for one orientation over the other strongly affects the stereochemistry and reactivity of cyclohexanes.

cis-1-fluoro-4-methylcyclohexane

The two groups compete for the equatorial positions and the corresponding ΔG° = -1.45 kcal/mol (-1.70 - 0.25), the larger methyl winning out over the smaller fluorine.

trans-1-fluoro-4-methylcyclohexane

The ΔG° (diaxial ⇌ diequatorial) for trans-1-fluoro-4-methylcyclohexane is - 1.95 kcal/mol (-1.70 for CH3 plus 0.25 for F).

How long do these conformations last?

Thus, the boat cyclohexane is not a normally isolable species, the twist-boat form is present in very small amounts, and the chair form is the major conformer.

Stability of cycloalkanes

To find out whether there is something special about the stability of cycloalkanes, we could compare their heats of combustion with those of the analogous straight-chain alkanes. Such a direct comparison is flawed since the empirical formula of cycloalkanes (CnH2n) differs from that of normal alkanes (CnH2n+2) by two hydrogens.

To predict the more stable conformer...

To predict the more stable conformer of a more highly substituted cyclohexane, the cumulative effect of placing substituents either axially or equatorially must be considered, in addition to their potential mutual 1,3-diaxial or 1,2-gauche interactions. For many cases, we can simply apply the values of Table 4-3 for a prediction.

True or False: Cycloalkanes have their own names under IUPAC rules.

True!

True or False: Cycloalkanes' properties are generally different from those of their acyclic analogs with the same number of carbons.

True!

how do we build cycloalkanes?

We can construct a model of a cycloalkane by removing a hydrogen atom from each terminal carbon of a model of a straight-chain alkane and allowing these carbons to form a bond.

How do we compare cycloalkane and alkane stability?

We can rewrite the formula for cycloalkanes as (CH2)n instead of (CnH2n). If we had an experimental number for the contribution of a "strain-free" CH2 fragment to the ΔH°comb, the corresponding ΔH°comb should be multiples of this number. If it's not, it might signal presence of strain.

Hashed-wedged line structures

We can use hashed-wedged line structures to depict the three-dimensional arrangement of substituted cycloalkanes. The positions of any remaining hydrogens are not always shown.

Requisite value for ΔH°comb(CH2)

When averaged over a large number of alkanes, this value approaches 157.4 kcal/mol, our requisite value for ΔH°comb(CH2)!

Calculating A-values: Example 2

When there are two substituents, it's favorable to have the larger substituent in the equatorial position

conformational isomerism

conformational isomerism is a form of stereoisomerism in which the isomers can be interconverted just by rotations about formally single bonds

The conformational preferences of disubstituted cyclohexanes can be predicted by

drawing the two possible chair conformations and comparing the A-values of the substituents

Cyclohexanes are generally more stable when substituents are in a(n) ___________ orientation

equatorial

t-butyl group

essentially locks the ring in the conformation that places it in an equatorial alignment