Professor David L. Van Vranken 201: Organic Reaction Mechanisms I

Topic 2: Theory

Reading: Ch. 1 of your sophomore textbook I. Fleming Molecular Orbitals and Organic Chemical Reactions, Ch. 2 & 3

Bradley, J. D.; Gerrans, G. C. “Frontier molecular orbitals. A link between kinetics and bonding theory.” J. Chem. Educ. 1973, 50, 463. The Need For Orbitals n Heisenberg said we can't specify the location of n We need orbitals to describe where the pairs of electrons want to be n Orbital phases help us see how one avoids the other, even though they are in the same orbital

n There are three basic types of orbitals 1. Atomic Orbitals 2. Hybrid Atomic Orbitals 3. Molecular Orbitals

Let's review them… 1. Atomic Orbitals - Review n There are four types of atomic orbitals: s, p, d, f n We can rationalize everything in this class using combinations of s and p orbitals n p orbitals are way higher in energy than s orbitals n decreases orbital energy

There’s a spherical inside the 2s orbital, but let’s ignore it. 2. Hybrid Atomic Orbitals - Review n Mixing Rule: When you mix two orbitals, you get two orbitals The reason you get two orbitals is because there are always two arbitrary phasing combinations n Three ways to mix one 2s and three 2p orbitals of 2nd row to give non-bonding orbitals, n

Note: electrons in higher energy orbitals ignore 1s are more reactive

planar n geometry correlates with hybridization (VSEPR .. sp3 p theory). If you could force to be planar, the distortion .. N N would end up in a super high energy p orbital. super nucleophilic 2. Hybrid Atomic Orbitals – Differences in Based on p Character n Assess p character in molecular orbitals corresponding to every bond and every lone pair because it predicts the reactivity of the electrons.

n More p character = more basic and more nucleophilic

n The magnitude of the effect is less pronounced for , which is less reactive overall than . 2. Quantitative Differences in Reactivity based on p Character n More p character in C-H sigma bonds correlates with lower BDE is defined as the Bond Dissociation Energies. (Compare only C-H bonds) energy required for homolysis in a hypothetical reaction:

n BIG Caution: assign hybridization AFTER considering . If you don’t consider resonance then you’re not really thinking about molecular orbitals. 3. Molecular Orbitals – Six Types of “Frontier” Molecular Orbitals n Arrows start from filled orbitals and end on un-filled orbitals. There are six canonical classes of frontier molecular orbitals that are used for . n Commit these canonical orbitals, and their relative energies to memory.

n Since there are only three types of filled FMOs and three types of unfilled FMOs, that means that there are only 3x3= 9 types of non-concerted elementary chemical reactions. We’ll spend the rest of this quarter talking about these nine types of interactions between filled and un-filled orbitals.

n Note that unfilled molecular orbitals are always higher in energy than filled molecular orbitals. (Aufbau principle). 3. Molecular Orbitals - M.O. Interaction Diagrams n Perturbation theory says that you get more orbital Orbital Interaction Energy, (I.E.) by Interaction = Efilled-Eempty mixing MOs that are closer Energy in energy

n M.O. Interaction diagrams are used to graphically depict the energetic consequences that result from perturbation of molecular orbitals through pair-wise mixing.

n If you could predict which filled orbitals are higher in energy and which unfilled orbitals are lower in energy, then you could predict which reactions would be fast and which reactions would be slow. You’ll spend the rest of the quarter practicing those predictions. 3. Molecular Orbitals – FRONTIER Molecular Orbitals n When two reactants interact, every filled orbital in one reactant interacts with every filled orbital in the other reactant. We can quantify that with perturbation theory resulting in a mathematical equation with lots of terms.

n When two reactants interact, most of the orbital interactions are not energetically favorable. H3N H3CBr A complex summation of The summed energy from etc. orbital interactions... orbital interactions usually etc. orbital overlap comes from a single S E -E interaction: between the all MOs filled empty highest occupied molecular LUMO EMO HOMO orbital (HOMO) in one reactant, reduces to... and the lowest unoccupied molecular orbital (LUMO) in the orbital overlap etc. E -E other reactant. The HOMO and etc. HOMO LUMO LUMO are the frontier orbitals. 3. Molecular Orbitals - The Importance of Orbital Overlap n Correct symmetry is required for effective overlap. Graphically, like phases to constructive interactions, but unlike phases lead to destructive interactions.


s s p p p or spn p or spn p p energy lowering no net change n Bredt’s Rule: Bridgehead olefins are unstable

n p orbitals overlap more effectively when they are closer together. Longer bonds are less stable and more nucleophilic

E+ E+ p overlap = p closer p orbitals H C CH -0.285 ev = better overlap 2 2 C C C C EMO C C = more stable b3lyp/6-311+G** HC CH -0.306 ev 1.46 Å 1.20 Å = less reactive pi bond

86% C H mCPBA R 5 11 O C5H11 R

Capon, R. J.; Barrow, R. A. J. Org. Chem. 1998, 63, 75-83 Intrinsic Reactivity of Canonical MOs Used for Arrow-Pushing: l.p., pi bonds, sigma bonds

n Generally the reactivity of lone pairs pi bonds sigma bonds nucleophilic groups used for arrow log 10 21 pushing follows the order: l.p. > pi > N:

sigma. 20

) e

n Electronegativity plays an important g

r a

role in determining nucleophilicity. h

c 15

g n i 11.6 11.5

r 10 10 o

n O: C C g

n You usually won’t have a problem i ( 10 identifying the most reactive pair of s

electrons in a . O





t 2.9 i 5

10 2.7 c

i 10

l 1.6 i 10 C N h C H

p F: 0

o 10

e l

c 0 10-3.7 C C sCC u -3.2

n 10

C O c i C N -5.1

s 10

n i

r C O

t -5

n i 10-8.7 C F -10

Based on MO energies calculated with B3LYP/6-31++G(d,p) versus the LUMO for H3CCH=O. Assumes equal orbital overlap. Intrinsic Reactivity of Canonical MOs Used for Arrow-Pushing n How accurate are the intrinsic reactivitivities of the canonical MOs? Maybe ±105 ???? one functional log n Lot’s of the lower energy FMOs will have similar group reactivity, but usually, it won’t be difficult to identify 15 the most reactive frontier orbital. H 1012.4 C N: ) l.p.

n Remember that generally: l.p. > pi > sigma e H H g

r 10







r o

n 5 2.9

g 10

i H


s C N

Suggest a plausible arrow-pushing mechanism: O

H p H



o 0 sCC


H CH3 t N N i

H C I c

3 i l

S S i h

warm p

o -5

excess and e + l NH2 c

I- u n


c i

s -10 n

i H

r -12.1

t 10

n C N O N i Gabriel, et al. H s H s O s F Chem. Ber. 1890, 2478 -15 lots of MOs w/ similar reactivity The Importance of Hybridization and p Character n More p character = more nucleophilic lone pairs pi bonds sigma bonds log n Less p character = less nucleophilic 1021 N:


) e

n p orbitals overlap more effectively when they g

r a are closer together. h

c 15


Longer bonds are less stable and more n

i 11.5

r 10 o

nucleophilic n C C


i ( 10 8

s 10 O




y t

i 5 2.9 2.7 c

i 10 10 l i N: h C H p 101.4

o C H

e l

c 0 sCC

u n


c 10 i

s N:


i r

t -5

n i 10 -9.3 C H -10 Effect of on the Energy of Frontier Orbitals n Longer bonds are more nucleophilic. n Longer bonds are easier to break.

n That is why: AlH4- is more nucleophilic than BH4- n That is why: SN2 reactions with R—I are faster than SN2 reactions with R-Cl The Effect of Conjugation on the Energy of Filled and Unfilled Frontier Orbitals n Pi conjugation raises the HOMO and lowers the LUMO

n That is why: conjugated non-conjugated

R+ faster than R+

: Nu faster than : Nu

even though more stable than Summary of FMO Trends