Stereochemistry of Alkanes and Cycloalkanes Chapter 2. Continue Stereochemistry of Alkanes and Cycloalkanes

The Shapes of Molecules The systematic study of the shapes molecules and properties from these shapes is stereochemistry A molecule may assume different shapes, called conformations صورتندی, that result from rotation about a carbon-carbon single bond,that are in equilibrium at room temperature (the conformational isomers are called conformers)

Representing Conformations Representing three dimensional conformers in two dimensions is done with standard types of drawings Sawhorse representations: these view the C-C bond from an oblique angle and indicate spatial orientations by showing all the C-H bonds. Newman projections: these site along a particular C-C bond and represent the two carbon atoms by a single circle. Substituents on the front carbon are represented by lines going to the center of the circle, and substituents on the rear carbon are indicated by lines going to the edge of the circle.

Although there are many possible conformations available to a particular molecule; each molecule will spend most of its time in its most stable conformation. The most stable conformation for any molecule is the one that minimizes the mutual repulsion of bonded electron clouds on adjacent carbons.

2.1 Conformations of Ethane Conformers interconvert rapidly and a structure is an average of conformers Molecular models are three dimensional objects that enable us to visualize conformers

Conformations of Ethane staggered conformation eclipsed conformation

Ethane’s Conformations The most stable conformation of ethane has all six C–H bonds away from each other (staggered) The least stable conformation has all six C–H bonds as close as possible (eclipsed) in a Newman projection – energy due to torsional strain

This increased energy due to eclipsing interactions is called torsional strain and is one kind of strain energy. Torsional strain is due to mutual repulsion between electron clouds as they pass by each other in eclipsed conformers

DG ~ 3 kcal/mol torsional strain (eclipsing strain) lower energy higher energy Ea ~ 3 kcal/mol = barrier to free rotation (but at RT most molecules have KE > Ea so rotation is essentially “free”) krot ~ 106 s-1 3 DG

Ethane’s Conformations

2.2 Conformations of Propane Propane (C3H8) torsional barrier around the carbon–carbon bonds 14 kJ/mol Eclipsed conformer of propane has two ethane-type H–H interactions and an interaction between C–H and C–C bond

Propane conformations

2.3 Conformations of Butane anti conformation has two methyl groups 180° away from each other Rotation around the C2–C3 gives eclipsed conformation Staggered conformation with methyl groups 60° apart is gauche conformation

Conformations of Butane

CH3–CH2–CH2–CH3 I anti (180º) II III gauche (60º) IV V gauche (60º) VI gauche ~ 0.8 kcal higher energy than anti - van der Waals repulsions = steric strain eclipsed: 3 kcal torsional strain + 0.3 kcal each CH3-H eclipse + ~ 3 kcal each CH3-CH3 eclipse

Gauche conformation: steric strain

Eclipsed Conformations of Butane

Conformations of Butane

جمعیت صورت بندی های گوناگون طبق معادله زیر به دست می آید. DG° = -RT ln Keq percentage

DS° = -R ln w , T = 298 K , R = 1.987 cal/mol.K w: Number of states DS° = -R ln 2 = -1.38 cal

at 298 K DG° = DH° - TDS° DG° = -0.8 x 1000 – 298(-1.38) DG° = -388.8 cal= -0.39 kcal DG° = -RT ln Keq Keq = 1.9 at 298 K

1-chloropropane Some experiments show that G conformer is more stable than A in both 1-chloropropane. 1-Durig, J. R.; Godbey, S. E.; Sullivan, J. F. J Chem Phys 1984, 80, 5983. 2- Barnes, A. J.; Evans, M. L.; Hallam, H. E. J Mol Struct 1983, 99, 235.

vdw radii inc. bond length inc

Stability of Cycloalkanes: The Baeyer Strain Theory In 1885, Baeyer proposed a theory to explain the apparent lack of cyclic alkanes having certain ring sizes. More specifically only 5 and 6 membered cycloalkane rings were known but smaller and larger rings could not be prepared. Baeyer theorized that these could not be prepared because their bond angles would necessarily deviate from the preferred sp3 bond angle of 109.5 degrees. This deviation would cause such angle strain that the rings would be too unstable to exist.

2.4 Stability of Cycloalkanes: The Baeyer Strain Theory Baeyer (1885): since (sp3) carbon prefers to have bond angles of approximately 109°, ring sizes other than five and six may be too strained to exist Rings from 3 to 30 C’s do exist but are strained due to bond bending distortions and steric interactions

Compound Structure Angle Strain 109-60=49 90 degrees 109-90=19 Baeyer Bond Angle Angle Strain Cyclopropane 60 degrees 109-60=49 Cyclobutane 90 degrees 109-90=19 Cyclopentane 108 degrees 109-108=1 Cyclohexane 120 degrees 109-120= -11

Angle Strain

Stability of Cycloalkanes Heats of combustion can be used to measure the total amount of energy strain in a compound. The notion here is that the more strained a compound, the higher is its energy content and the more heat delivered per CH2 unit upon combustion to CO2 + H2O. Alkane + O2 CO2 + H2O + Heat

Bayer’s Theory Busted Heats of combustion data indicate that Baeyer's theory was not fully correct. Cyclopropane and cyclobutane are quite strained but cyclopentane is more strained then first predicted while cyclohexane is less strained. For larger rings, there is no regular increase in strain and rings of more than 14 carbons are strain free.   Why was Baeyer's theory incorrect? Baeyer assumed that all cycloalkanes are flat when in fact most adopt a puckered 3-D conformation. Furthermore, he did not consider the contribution of torsional strain to the overall strain energy of a molecule.

2.5 The Nature of Ring Strain Rings larger than 3 atoms are not flat (planar) Cyclic molecules can assume nonplanar conformations to minimize angle strain and torsional strain by ring-puckering Larger rings have many more possible conformations than smaller rings and are more difficult to analyze

° ° poor overlap = bond angle strain 22_499 poor overlap = bond angle strain (i.e., 109.5º sp3 in 60º triangle) No "head-on" overlap of atomic orbitals C 109.5 ° 6 ° C C plus (a) (b) all H’s eclipsed = torsional strain

Summary: Types of Strain Angle strain - expansion or compression of bond angles away from the preferred 109.5 Torsional strain - eclipsing of bonds on neighboring atoms Steric strain - repulsive interactions when two atoms or groups bump in to one another

Torsional Strain

Steric Strain

Strain Energies

2.6 Cyclopropane: An Orbital View 3-membered ring must have planar structure Symmetrical with C–C–C bond angles of 60° Requires that sp3 based bonds are bent (and weakened) All C-H bonds are eclipsed

2.7 Conformations of Cyclobutane and Cyclopentane Cyclobutane has less angle strain than cyclopropane but more torsional strain because of its larger number of ring hydrogens Cyclobutane is slightly bent out of plane - one carbon atom is about 25° above The bend increases angle strain but decreases torsional strain

slightly more angle strain, but less eclipsing strain planar, 90º but all eclipsed “puckered”, 88º slightly more angle strain, but less eclipsing strain

Cyclopentane “envelope” relieves eclipsing planar, 108º Planar cyclopentane would have no angle strain but very high torsional strain Actual conformations of cyclopentane are nonplanar, reducing torsional strain Four carbon atoms are in a plane The fifth carbon atom is above or below the plane – looks like an envelope planar, 108º but all eclipsed “envelope” relieves eclipsing

سیکلو هگزان اطلاعات حاصل از سوختن نشان دهنده تحت فشار نبودن حلقه است. اگر مسطح بود زاویه حلقه 120 می شود. در کنفورمر صندلی زاویه 109.5 وهمه هیدروژن ها نامتقابل هستند. فشار زاویه ای وفشار پیچشی وجود ندارد.

سیکلو هگزان محوری Move this carbon down استوایی Axial Move this carbon up Equatorial

پیکر بندی های سیکلو هگزان محوری Move this carbon down استوایی Axial Move this carbon up Equatorial The equatorial conformer of methyl cyclohexane is more stable than the axial by 7.6 kJ/mol

Bromocyclohexane When bromocyclohexane ring-flips the bromine’s position goes from equatorial to axial and so on At room temperature the ring-flip is very fast and the structure is seen as the weighted average

1,3-Diaxial Interactions Difference between axial and equatorial conformers is due to steric strain caused by 1,3-diaxial interactions Hydrogen atoms of the axial methyl group on C1 are too close to the axial hydrogens three carbons away on C3 and C5, resulting in 7.6 kJ/mol of steric strain

سیکلو هگزان X Strain (kcal/mol) -F 0.12 -Cl 0.25 -Br -OH 0.5 -CH3 0.9 -CH2CH3 0.95 -CH(CH3)2 1.1 -C(CH3)3 2.7 -C6H5 1.5 -COOH 0.7 -CN 0.1

2.12 Boat Cyclohexane Cyclohexane flips through a boat conformation ~29 kJ/mol (7.0 kcal/mol) less stable than chair

boat conformation سیکلو هگزان Less stable than chair cyclohexane due to steric and torsional strain C-2, 3, 5, 6 are in a plane H on C-1 and C-4 approach each other closely enough to produce considerable steric strain Four eclipsed H-pairs on C- 2, 3, 5, 6 produce torsional strain

Conformational Analysis Conformational aspects of six-membered rings Chair-chair inversion by half-chair and twist boat conformations half-chair twist-boat half-chair Half-chair is highest-energy conformer (~ 11 kcal mol-1above energy of chair) two chair forms are degenerate – equally populated at 25 °C

2. 13 Conformational Analysis of Disubstituted Cyclohexanes In disubstituted cyclohexanes the steric effects of both substituents must be taken into account in both conformations There are two isomers of 1,2-dimethylcyclohexane: cis and trans

2.14 Conformational Analysis of Disubstituted Cyclohexanes In the cis isomer, both methyl groups same face of the ring, and compound can exist in two chair conformations Consider the sum of all interactions In cis-1,2, both conformations are equal in energy

Cis-1,2-dimethylcyclohexane

Trans-1,2-Dimethylcyclohexane Methyl groups are on opposite faces of the ring One trans conformation has both methyl groups equatorial and only a gauche butane interaction between methyls (3.8 kJ/mol) and no 1,3-diaxial interactions The ring-flipped conformation has both methyl groups axial with four 1,3-diaxial interactions

Trans-1,2-Dimethylcyclohexane Steric strain of 4  3.8 kJ/mol = 15.2 kJ/mol makes the diaxial conformation 11.4 kJ/mol less favorable than the diequatorial conformation trans-1,2-dimethylcyclohexane will exist almost exclusively (>99%) in the diequatorial conformation

Trans-1,2-Dimethylcyclohexane

Trans-1,2-Dimethylcyclohexane

Axial/Equatorial Relationships

t-Butyl Groups

t-Butyl Groups

t-Butyl Groups

Most stable conformation of Menthol?

Solution:

2.15 Conformations of Polycyclic Molecules Decalin consists of two cyclohexane rings joined to share two carbon atoms (the bridgehead carbons, C1 and C6) and a common bond

Decalin

2.16 Conformations of Polycyclic Molecules Two isomeric forms of decalin: trans fused or cis fused In cis-decalin hydrogen atoms at the bridgehead carbons are on the same face of the rings In trans-decalin, the bridgehead hydrogens are on opposite faces Both compounds can be represented using chair cyclohexane conformations Flips and rotations do not interconvert cis and trans

Cis- and trans- decalins

Steroids

Bicyclic Compounds

Camphor