Ch.4 Stereochemistry of Alkanes and Cycloalkanes
stereochemistry: 3-dimensional aspects of molecules
4.1 Conformation of Ethane
conformation: the different arrangements of atoms that result from
rotation about a single bond
conformers: a specific conformation (conformational isomer); same
connections of atoms
H
H
H
C
rotate
H
C
H
H
H
C
H
H
H
H
C
H
Ch.4 Stereochemistry of Alkanes and Cycloalkanes
Sawhorse representation
H
Newman projection
H
C
H
H
back carbon
H
H
H
C
H
H
front carbon
H
H
H
Ch.4 Stereochemistry of Alkanes and Cycloalkanes
Energy barrier for rotation: not perfectly free rotation about σ-bonds
4 kJ/mol (1.0 kcal/mol)
HH
H
H
H
H
H
H
staggered conformation
rotate 60o
4 kJ/mol
H
H
HH
4 kJ/mol
eclipsed conformation
rotational barrier:
12kJ/mol (2.9 kcal/mol)
Ch.4 Stereochemistry of Alkanes and Cycloalkanes
- the 12 kJ/mol (2.9 kcal/mol) of extra energy present in the eclipsed
conformation of ethane is called torsional strain
• Torsional strain is due to repulsion between electron clouds in the
C-H bonds as they pass close by each other in the eclipsed conformer
HH
H
H
HH
eclipsed conformation
Ch.4 Stereochemistry of Alkanes and Cycloalkanes
A graph of potentiol energy versus bond rotation in ethane
HH
HH
H
H
HH
H
H
HH
HH
H
H
HH
240o
120o
HH
360o
Energy
0o
H
H
HH
12 kJ/mol
180o
H
60o
H
300o
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
Ch.4 Stereochemistry of Alkanes and Cycloalkanes
4.2 Conformation of Propane
6 kJ/mol (1.4 kcal/mol)
H3CH
CH3
H
H
H
H
H
staggered conformation
rotate 60o
H
4.0 kJ/mol H
HH
4.0 kJ/mol
eclipsed conformation
rotational barrier:
14 kJ/mol (3.4 kcal/mol)
Ch.4 Stereochemistry of Alkanes and Cycloalkanes
4.3 Conformation of Butane
H
H3C
H
CH3
H
CH3
CH3
H
H
H
H
H
H
CH3
H
H
CH3
H
anti
gauche
anti conformation: two large groups are in the opposite side
eclipsed conformations
gauche conformation: two large groups are 60o apart
Ch.4 Stereochemistry of Alkanes and Cycloalkanes
Eclipsed conformations
6.0 kJ/mol
H3CH
6.0 kJ/mol
H3C
H
HH 4.0 kJ/mol
total cost: 16 kJ/mol (3.8 kcal/mol)
eclipsed
Ch.4 Stereochemistry of Alkanes and Cycloalkanes
Eclipsed conformations
11 kJ/mol (2.6 kcal/mol)
H3CCH3
4.0 kJ/mol
H
H
HH 4.0 kJ/mol
total cost: 19 kJ/mol (4.6 kcal/mol)
least stable eclipsed
Ch.4 Stereochemistry of Alkanes and Cycloalkanes
Gauche conformation: 3.8 kJ/mol (0.9 kcal/mol) unstable due to steric
strain between two methyl groups
3.8 kJ/mol (0.9 kcal/mol)
H
H
H
H
CH3
H
CH3
H
H
H
gauche
H
H
H
H
H
H
- hydrogen atoms on methyl groups interact
steric strain: repulsive interaction that occurs when atoms are too closer
Ch.4 Stereochemistry of Alkanes and Cycloalkanes
CH3
CH3
Four possible
conformations of
n-butane
H
H
H
H3 C
H
H
H
H
H
CH3
gauche
anti
staggered
H3CH
H3 C
H
H3CCH3
HH
eclipsed
H
H
HH
eclipsed
Ch.4 Stereochemistry of Alkanes and Cycloalkanes
Energy
A graph of potentiol energy versus bond rotation in buthane
19 kJ/mol
16 kJ/mol
3.8 kJ/mol
180o
120o
CH3
H
H
CH3
anti
H3C
H
HH
H3C
H
H
H
H
gauche
60o
0o
CH3
H3CH
H
H
60o
H3CCH3
H
H
HH
120o
CH3
H
CH3
H
H
H
gauche
CH3
HCH3
HH
180o
H
H
CH
H 3
H
H
CH3
anti
Ch.4 Stereochemistry of Alkanes and Cycloalkanes
Energy costs for interactions in alkane conformers
HH
4.0 kJ/mol
(1.0 kcal/mol)
torsional strain
H3CH
6.0 kJ/mol
(1.4 kcal/mol)
mostly torsional strain
11 kJ/mol
(2.6 kcal/mol)
H3CCH3
torsional + steric strain
CH3
3.8 kJ/mol
(0.9 kcal/mol)
CH3
steric strain
Ch.4 Stereochemistry of Alkanes and Cycloalkanes
• the most stable conformation of any alkanes has the C-C bonds in staggered
arrangements and large substituents arranged anti to each other
H H
H
H H
H H
H H
H
H
H
H
H H
H H
HH
H
zig-zag conformation
• At room temperature, enough thermal energy is present to cause rotation
around σ-bonds to occur rapidly so that all conformations are in equilibrium.
At any given time, however, a larger percentage of molecules will be found
in a more stable conformation than in a less stable one.
Ch.4 Stereochemistry of Alkanes and Cycloalkanes
Practice
Conformation of 1-chloropropane
Newman projections
H3C
CH3
CH3
H
H
H
Cl
H
H
H
H
Cl
Cl
H
H3CH
H
H
H3CCl
H
Cl
H
H
HH
Ch.4 Stereochemistry of Alkanes and Cycloalkanes
4.4 Stability of Cyclohexanes: The Baeyer Strain Theory
Angle strain (Baeyer strain): the strain induced in a molecule when a
bond angle deviates from the ideal tetrahedral value
bond angles for hypothetical planar cycloalkane structures;
108o
60o
90o
109o (tetrahedral angle)
120o
Ch.4 Stereochemistry of Alkanes and Cycloalkanes
Heat of Combustion of Cycloalkanes
ring strain: total energy of the compound- the energy of a strain-free
reference compound
heat of combustion: the amount of heat released when a compound burns
completely with oxygen
; used for determination of starin energies of cycloalkanes
; the more energy (strained) a compound contains, the more energy (heat)
is released on combistion
(CH2)n +
3n
O2
2
nCO2 + nH2O + heat
Ch.4 Stereochemistry of Alkanes and Cycloalkanes
cycloalkane strain energies, calculated by taking the difference between
cycloalkane heat of combustion per CH2 and acyclic alkane heat of
combustion per CH2, and multiplying by the number of CH2 units in a ring.
Small and medium rings are strained, but cyclohexane ring is strain-free.
• the strain molecules (cyclopropane, cyclobutane) are unstable and
highly reactive
• cyclopentane, cyclohexane are srtain free
• medium rings C7-C13 are srtained: 115-120o
• larger rings are unstrained ≥C14
Ch.4 Stereochemistry of Alkanes and Cycloalkanes
cycloalkane strain energies
Ch.4 Stereochemistry of Alkanes and Cycloalkanes
4.5 The Nature of Ring Strain
• rings are not flat; 3-dimensional conformations
• torsional strain due to eclipsed C-H bonds in ring systems
The conformation of cyclopropane, showing the eclipsing of neighboring
C-H bonds that give rise to torsional strain.
H
H
H
HH
eclipsed
H
HH
eclipsed
H
H
H
H
Ch.4 Stereochemistry of Alkanes and Cycloalkanes
Cycloalkanes adopt their minimum-energy conformation for the
combination of three reasons:
• Angle strain: the strain due to expansion or compression of bond angles
• Torsional strain: the strain due to eclipsing of bonds on neighboring atoms
• Steric strain: the strain due to repulsive interactions when atoms approach
each other too closely
Ch.4 Stereochemistry of Alkanes and Cycloalkanes
4.6 Cyclopropane: An Orbital View
colorless gas (bp= -33 oC); first prepared by reaction of sodium with 1,3dibromopropane
2 Na
Br
+ 2 Na Br
Br
bent bond:
C
C
poor overlap
C
C
C
C
109o
A typical alkane C-C bond
A bent cyclopropane C-C bond
Ch.4 Stereochemistry of Alkanes and Cycloalkanes
4.7 Conformations of Cyclobutane and Cyclopentane
Cyclobutane
less angle strain than cyclopropane but more torsional strain because of its
larger number of ring hydrogens
; total strain of cyclobutane- 110.4 kJ/mol (26.4 kcal/mol)
; total strain of cyclopropane- 115 kJ/mol (27.5 kcal/mol)
; not flat but puckered → increase angle strain but decrease torsional strain
H
H
H
not quite
eclipsed
H
H
H
H
H
H
H
H
H
H
HH
not quite
eclipsed
H
Ch.4 Stereochemistry of Alkanes and Cycloalkanes
Cyclopentane
total strain of cyclopentane- 26.0 kJ/mol (6.2 kcal/mol)
; not planar but envelop conformation
H
H
H
H
envelop
H
H H
H
HH
Ch.4 Stereochemistry of Alkanes and Cycloalkanes
4.8 Conformations of Cyclohexane
• unstrained
chair conformation: bond angle 111.5o (close to the ideal 109.5o
tetrahedral angle)
H
H
H
HH
H
HH
H
H
chair
H
H
H
H
CH2
H
H
CH2
H
H
H
H
all staggered conformation
Ch.4 Stereochemistry of Alkanes and Cycloalkanes
• drawing chair conformation: draw parallel three bonds pairs
this bond is in back
this bond is in front
Ch.4 Stereochemistry of Alkanes and Cycloalkanes
4.9 Axial and Equatorial Bonds
H
H
H
H
HH
H
H
H
H
H
H
H
H
H
H
axial
HH
H
H
top view
H
equatorial
Ch.4 Stereochemistry of Alkanes and Cycloalkanes
4.10 Conformational Mobility of Cyclohexane
ring-flip
the energy barrier for the ring flipping is small: fast ring flipping is
observed ( two conformers are in fast equilibrium)
Ch.4 Stereochemistry of Alkanes and Cycloalkanes
ring flipping
H
Br
H
ring-flip
Br
Ch.4 Stereochemistry of Alkanes and Cycloalkanes
Hax
Ea= 45 kJ/mol
Heq
Heq
chair
Hax
- rapid interconversion at 25 ℃
(Ea= 45 kJ/mol (10.8 kcal/mol), 20 kcal/mol available at 25 ℃)
- Hax and Heq are indistinguishable by 1H NMR at 25 ℃
- at < -70 oC, Hax and Heq are distinguishable by 1H NMR
Ch.4 Stereochemistry of Alkanes and Cycloalkanes
4.11 Conformation of Monosubstituted Cyclohexanes
• two conformers of a monosubstituted cyclohexane are in fast equilibrium
at room temperature but not equally stable
CH3
ring-flip
CH3
∆ E = - RT ln K
Ch.4 Stereochemistry of Alkanes and Cycloalkanes
CH3
CH3
ring-flip
Ch.4 Stereochemistry of Alkanes and Cycloalkanes
A
B
energy barrier vs rate constant
energy barrier
at RT
5 kcal/mol
109 sec-1
10 kcal/mol
105 sec-1
15 kcal/mol
102 sec-1
> 20 kcal/mol
Ch.4 Stereochemistry of Alkanes and Cycloalkanes
A
B
∆ G = - RT ln K
free energy vs % of isomer
free energy
more stable
isomer(%)
1.0 kcal/mol
80%
1.3 kcal/mol
90%
2.3 kcal/mol
98%
4.1 kcal/mol
>99.9%
Ch.4 Stereochemistry of Alkanes and Cycloalkanes
1,3-diaxial interaction: steric strain, butane gauche interaction
H
CH3
7.6 kJ/mol
(1.8 kcal/mol)
H
H
H
CH3
7.6 kJ/mol ~ 95% equatorial methyl preference
Heq
Heq
Hax Hax Hax
Heq
Heq
Hax Hax CH3
Ch.4 Stereochemistry of Alkanes and Cycloalkanes
butane gauche interactions
3.8 kJ/mol
(0.9 kcal/mol)
CH3
butane gauche
H
CH3
H
H
H
H
H
CH3
H
H
CH3
H
H
H
CH3
1,3-diaxial interaction:
butane gauche interaction (x2)
3.8 x 2 = 7.6 kJ/mol
Ch.4 Stereochemistry of Alkanes and Cycloalkanes
Steric Strain in Monosubstituted Cyclohexanes
H
X
H
H
X
R
(kJ/mol)
(kcal/mol)
F
0.5
0.12
Cl
1.0
0.25
Br
1.0
0.25
OH
2.1
0.5
CH3
3.8
0.9
CH2CH3
4.0
0.95
CH(CH3)2
4.6
1.1
C(CH3)3
11.4
2.7
C6H5
6.3
1.5
COOH
2.9
0.7
CN
0.4
0.1
Ch.4 Stereochemistry of Alkanes and Cycloalkanes
4.12 Conformational Analysis of Disubstituted Cyclohexanes
• all steric interactions in both possible chair conformations must be
analyzed
CH3
CH3
CH3
H
H
CH3
H
CH3
H
CH3
1 gauche interaction (3.8 kJ/mol)
2 diaxial interaction (2 x 3.8 kJ/mol)
total strain = 11.4 kJ/mol (2.7 kcal/mol)
Ch.4 Stereochemistry of Alkanes and Cycloalkanes
CH3
CH3
H
H
H
CH3
H
CH3
CH3
H
H
1 gauche interaction
(3.8 kJ/mol)
CH3
4 diaxial interaction
(15.2 kJ/mol)
11.4 kJ/mol more stable
trans-1,2-dimethylcyclohexane will exist almost exclusively
(>99%: 2.7 kcal/mol) in the diequatorial conformation
Ch.4 Stereochemistry of Alkanes and Cycloalkanes
Practice
CH3
Conformation of cyclohexane
CH3 CH3
CH3
CH3
CH3
more stable
CH3
CH3
CH3
CH3
CH3
CH3
equivalent
Ch.4 Stereochemistry of Alkanes and Cycloalkanes
Practice
Conformation of cyclohexanes
Br
Br
Br
more stable
Br
Br
more stable
Br
Ch.4 Stereochemistry of Alkanes and Cycloalkanes
Ch.4 Stereochemistry of Alkanes and Cycloalkanes
4.13 Boat Cyclohexane
H
H
H
H
H
H
H
H
H
H
H
H
boat
rel E = 29 kJ/mol (7.0 kcal/mol)
twist boat
rel E = 23 kJ/mol (5.5 kcal/mol)
Ch.4 Stereochemistry of Alkanes and Cycloalkanes
Ch.4 Stereochemistry of Alkanes and Cycloalkanes
Hax
Ea= 45 kJ/mol
Heq
Heq
chair
Hax
twist boat
half chair
rel E = 45 kJ/mol
rotational
barrier
rel E = 23 kJ/mol
Ch.4 Stereochemistry of Alkanes and Cycloalkanes
4.14 Conformations of Polycyclic Molecules
H
trans-Decalin
0 kcal/mol
H
H
cis-Decalin
+ 2.2 kcal/mol
H
Ch.4 Stereochemistry of Alkanes and Cycloalkanes
Ch.4 Stereochemistry of Alkanes and Cycloalkanes
H
trans-decalin can adopt only
one chair-chair conformation
H
H
H
H
H
cis-decalin can adopt two chair-chair conformations
Ch.4 Stereochemistry of Alkanes and Cycloalkanes
CH3
H
CH3 H
H
H
HO
Cholesterol (a steroid)
CH3
HO
CH3
Ch.4 Stereochemistry of Alkanes and Cycloalkanes
bridgehead carbon: carbon shared by two rings
A 1-carbon bridge
bridgehead carbons
A 2-carbon bridge
Norbornane
(Bicyclo[2.2.1]heptane
O
Camphor
Chemistry @
Work
Molecular
Mechanics
Ch.4
Stereochemistry
of Alkanes
and Cycloalkanes
molecular mechanics: find the minimum energy conformations of
molecules by mathematical calculations
Etotal = Ebond stretching + Eangle strain + Etorsional strain + Evan der Waals
- particularly useful in pharmaceutical research
; search the molecules which complementary fit with the receptor protein
; design the drug molecule and synthesis them