Strain and StabilityChapter 2

- Reactivity of a new molecule-Prediction of the lowest energy conformation of a new molecule--> a rapid evaluation of strains and stabilizing effects

2.1 Thermochemistry of stable molecules (strain and stability)

2.1.1 The concepts of internal stain and relative stability

Strain:

Is typically associated with a conformational distortion or nonoptimal bonding situation

relative to standard organic structures. The reference structure lacks the particular strain.

Internal energy:

It is the energy held or stored within a molecule. Part of this energy can be released when given an outlet such as a chemical reaction.

When a molecule has a higher potential energy (internal energy), it is less stable and/or more strained.

2.1.2 Types of energyGibbs free energy (ΔGo): It is change in ΔGo between two different chemical states that determines the position of equilibrium between these states.

A B←→

R = 4.184 kJ/molΔHo : enthalpy (kcal/mol)ΔSo : entropy (cal/mol·K)

Exergonic, when the Gibbs free energy of B is lower than A, spontaneous conversionEndergonic, when the Gibbs free energy of B is higher than A

Keq is influenced by temperature

Enthalpy (ΔHo): The change in enthalpy is defined as the change in heat between two different compositions of an ensemble of molecules at constant pressure if no work is done.

Exothermic, negative ΔHo

Endotherimic, positive ΔHo

Entropy (ΔSo): is a measure of the disorder of the system. -> degrees of freedom

the more degrees of freedom, the greater the entropy.

There are three different kinds of degrees of freedom: translational, rotational and

vibrational.

Translational and rotational refer to the translation of the molecule throughout space and tumbling of the molecule, respectively.

Vibrational refers to every kind of internal motion of the molecule, such as bond stretches, bond rotations and various forms of bond angle vibrations.

While entropy is certainly important for significant changes in chemical structure (such as cyclization), often when comparing two similar structures, the difference in entropies will be fairly small. Thus, ΔHo is mainly considered in reactions.

2.1.3 Bond dissociation energies

Is defined as ΔHo.

(bond strength)

Homolytic cleavage

A larger BDE implies a less stable radical.

1. F > OH > NH2, the larger the electronegativity difference, the stronger the bond.

2. Shorter bonds are stronger bonds; O-H > N-H> C-H

3. F > Cl > Br > I; move down the periodic table, the valence orbitals of X get progressively larger. The larger orbital size leads to a size mismatch with the carbon valence orbitals, and this weakens the bond by decreasing orbital overlap.

4. Hybridization

C(sp)-H > C(sp2)-H > C(sp3)-H, more s character in a hybrid orbital makes the group

more electronegative and decreases the bond length.

5. Resonance

PhCH2-H (88 kcal/mol) and CH2=CH-CH2-H (86 kcal/mol)

6. O-O bonds of peroxides: generally very weak

2.1.4 An introduction to potential functions and surfaces: bond stretches

X. + Y.

X-YAnharmonic oscillator

Vibrational energy states

E = (n + ½)hv (n=0, ZPE) frequency = v = 1/(2π) √ k/μk = force constantμ = reduced mass, (m1 +m2)/m1m2

Infrared spectroscopy

v = 1/(2π) √ k/μk = force constantμ = reduced mass, (m1 +m2)/m1m2

v = 1/λ = v/c = 1/(2πc) √ k/μWavenumber(cm-1)

frequency

C-C C=C C≡C450-500 cm-1 1617-1640 cm-1 2100-2260 cm-1

C=C-C=O C=O1690 cm-1 1730 cm-1

O O-

+less double character

k

m1 m2Hooke’s law

v = 1/(2π) √ k/μ

1)

3)

2)

wavenumber the largest the lowest middle

O

Cl R

O

MeO R

O

Me R

O-

+Cl R

O-

MeO R+

2.2 Thermochemistry of reactive intermediates2.2.1 Stability vs persistence

1. stable; thermodynamic notion <-> unstable

2. persistent; kinetic notion (kinetically inert) <-> labile (reactive)

참조

1,3-butadiene ethylenemore stable less stable <- extra orbital interaction between C2 and C3more labile less labile

HOMO energy (ethylene)HOMO energy (butadiene) > LUMO energy (ethylene)LUMO energy (butadiene) <

Π

Π*

ψ1

ψ2

ψ3

ψ4

1,3-butadiene ethylene

Stability: determined by the energies of all the filled orbitalsLability (reactivity): must consider the energy of HOMO or LUMO

2.2.2 Radicals

1. BDE; methane > ethane > propane > isobutane <- radical stability 3o > 2o > 1o > methyl

2. Allyl and benzyl radicals -> substantially stabilized (resonance effect)

rotation barrier ~ 15.7 kcal/mol (resonance structure)Allylic radicalIn many cases, radical species are unstable but in some cases there are stable radical species.

Commercially available

2.2.3 Carbocations

Hydride ion affinity (HIA), ΔHo

A larger HIA implies a less stable carbocation.

1. Heteroatom effects

stability: NH2CH2+ > HOCH2

+ > FCH2+

X-CH2+

..+X=CH2

Consider both inductive and resonance effects2. Hybridization effects

stability: sp3 > sp2 > spConsider electronegativity

vinyl cation and phenyl cation: ~287 kcal/mol HIAverse Ethyl cation ~ 273 kcal/mol, propyl cation ~266 kcal/mol HIA

propargyl cation ~270 kcal/mol verse allyl cation ~256 kcal/mol

3. Aromaticity and antiaromaticity

> >stability:

HIA 201 212 258aromatic antiaromaticnon-aromatic

resonance effect

4. Planarity and pyramidalizationCarbocation: planar

Ring constraints prevent the ion from achieving Planarity. But 3o cation

Planar but 2o cation

relatively small difference in HIVs (9 kcal/mol)

Lifetimes of carbocations

3o carbocations: 10-10 s in water2o carbocations: 10-12 s in water

In solution

Carbocations are formed in solution by SbF5 (Olah, 1994, Nobel Prize)

2.2.4 Carbanions

Stability of carbanions is related to pKa values.The smaller pKa value implies a stronger acid.

aromatic

anti-aromatic

2.3 Relationships between structure and energetics-basic conformational analysis

2.3.1 Acyclic systems-torsional potential surfaces

ethane butanerotation barrier: 3kcal/mol

t1/2 = ln2/k

Barrier height

Similar; consider size and bond length

Lower than C-C, lone pair < C-H

Allylic (A1,3) strain

2.3.2 Basic cyclic systems

Cyclic propane

115o larger than H-C-H (106o)

Bent bonds (sp4~sp5)

(sp~sp2)

C-C-C, more p character to reduce bond angle (sp 180o, sp2 120o, sp3 109.5o) -> C-H more s character -> more acidic than alkane C-H

Strain energy of cyclopropane: 27.5 kcal/mol (results from deviation of bond angles from normal values andeclipsing C-H interactions)

Cyclobutane and cyclopentane

puckered conformationsStrain energy: 26.5 kcal/mol

very small barrier(1.45 kcal/mol)

Strain energy: 6.2 kcal/mol

Two forms are very nearly equal in energy and they interconvert very rapidly (the barrier is < 2 kcal/mol)

1’2’

3’

4’

5’

NH

N

N

O

NH2N

O

H (OH)OH

HO

1'2'3'4'

5'

Cyclohexane

Newman projection

A value: ΔGo of two structures (axial and equatorial)

similarconsider size and bond length

Not much difference

H RR

H

RR

Conformational interconversion of cyclohexane

Larger rings

cyclodecane~ 3 kcal/mol more stable

Bicyclic ring systems

spiro: a molecule has two rings and two share only one carbon in common

Strain energy

2.4 Electronic effects

2.4.1 interactions involving π systems

Substitution on alkenes:The more substitution, the more stable; interaction of a filled π(CH3) orbital withthe π* orbital.

steric effect

π*

π(CH3)

Stability, CH2=CH2 < CH2=CHMe < cis-CHMe=CHMe < trans-CHMe=CHMe

< CMe2=CMe2 < CHMe=CMe2

trans-alkenes are more stable than cis-ones.

Hyperconjugation: no-bond resonance

H

HH

H

H+

HH

-

Conformations of substituted alkenes:Eclipsed conformers are more stable than staggered ones.

2 kcal/mol more stable although there is steric hindrance.

HH

eclipsed staggered

filled π(CH3)

filled π filled π

filled π(CH3)

Repulsive interactions between filled π(CH3) and filled π

H

Attractive interaction π∗

filled π(CH3)

Repulsive interactions

C1C2

C3

C2-C3: strengthenedC1-C2:weakened

Allylic (A1,3) strain

H3C R

H

HO CH3

VO(acac)3

tBu-OOHhydroxyl group directing

epoxidation

H3C R

H

HO CH3

O

90%

H3C R

H

HO CH3

O

R = H10%

+

eclipsed; more stable A1,3 strain

H3C R

H

HO CH3

H3C R

CH3

H OHR = CH3; ~90%R = TMS; ~98%

H3C R

OH

H3C H

the most stable conformer

acac: acetoacetate

Carbonyl compounds

1 kcal/mol more stable

1-methylallyl cation

Conjugation

steric effectpreferred

Diels-Alderrxn

5 kcal/mol more stable

Aromaticity

Planar, cyclic, fully conjugated π systems

(4n+2)π electrons: aromatic, 4nπ e-: antiaromatic

Homoaromatic: systems in which a stabilized cyclic conjugated system is formed by bypassing a saturated atom.

Homoaromatic

Ha Hb Ha Hb

6π e- 6π e-

μ = 0.8 D (HBr; 0.828 D)

Aromatic compounds: ring current, downfield shift at 1H NMR spectra

Hdownfield (~7 ppm)

HHH

HHH

HH

H

H

HHH

H

H

H

HH

6H: -3 ppm12H: 9.3 ppm

AntiaromaticityPlanar, cyclic, fully conjugated π systems

4nπ e-

not square but rectangular structure

Cyclobutadiene: antiaromatic

Cyclooctatetraene: non-aromatic nonplanar

Cl SbCl5+ SbCl6-

aromatic

ClSbCl5

extremely slow antiaromatic

H pKa = 16

Ph

Ph

Ph

Ph

Ph

Ph pKa = 50

antiaromatic

aromatic

2.4.2 Effects of multiple heteroatomsBond length effects

The more substitution, the more stable; interaction of a filled π(CH3) orbital withthe π* orbital.

C-O and C-N are shorter than C-C, leading to increased steric strain.C-S is significantly longer than C-C.

OO

Rno 1,3-diaxial interaction

2-position 5-position

Orbital effects

D CA

..D C

A-

+

D: donorslone pair > bonding pairs, F < O < N

A: acceptorsF > O > N

n

σ*

n -> σ* interaction

H3CO Cl

HHO Cl

H3C

HH

CH2FNH2

CH3OCH2Cl

antiperiplanar

one antiperiplanar two antiperiplanar interactions-> more stable conformer

Anomeric effect

Pyranose sugars substituted with an electron-withdrawing group such as halogen oralkoxy at C-1 are often more stable when substituent has an axial orientation rather than an equatorial one.

n -> σ* interaction

O OR

axial

axialequatorial

antiperiplanar

Example)