Professional Documents
Culture Documents
12 Spring 2003
Lectures #1 & 2, 2/5,7/03
Outline
Discuss General Class Information (Professor Imperiali)
Recitations: Twice a week, beginning second week. Section changes should be made
through the 5.12 website. All changes must be made by Friday 2/14.
Problem Sets: Turn in to TA's box in Chem. Ed. office by 4pm on the due date.
Lowest grade will be dropped. No late work accepted.
Midterms: During class period. Lowest grade will be dropped. No make-up exams.
Vitalism: Belief that a "magic" vital force, present in plants and animals, is necessary for
the synthesis of organic compounds
1789: Antoine Laurent Lavoisier observed that organic compounds are composed
primarily of carbon and hydrogen
O
heat
Pb+NCO NH4+OH NH4+NCO C
H2N NH2
lead ammonium ammonium
cyanate hydroxide cyanate urea
inorganic organic
Why Carbon?
Carbon forms a variety of strong covalent bonds to itself and other atoms.
OH OH
O CH3 CH3
NH2
N NH H CH3 H
N
N N O H H H H
N H H
HO O
DNA Bases Hormones
O
OH OH H H H2N CH C OH
O O
H O
OH H CH 2
H HO H 2N CH C OH
H H HO
H OH
OH CH3
H OH
OH OH H
A. Ionic Bonding
Between atoms of widely different electronegativity (EN>2); usually a metal and
a non-metal; atoms held together by electrostatic attraction, not electron sharing
F + e F H = 78.3 kcal/mol
(electron affinity)
1s22s22pX22pY22pZ1 1s22s22p6 = [Ne]
Instead, each chlorine atom shares one valence electron with carbon so that every
atom has a filled octet.
Cl Cl
C 4 Cl Cl C Cl Cl C Cl
Cl Cl
Kekule Drawing
Each chlorine atom still has three unshared pairs of electrons (lone pairs).
How can you tell how many bonds and how many lone pairs an atom will have?
H 1 1 0
C 4 4 0
N 5 3 1
2nd row
O 6 2 2
F 7 1 3
Second row elements want to be surrounded by eight valence electrons (an octet).
e.g. Nitrogen wants three more electrons (three bonds, one lone pair).
N 3 X X N X X N X
X X
1. Multiple Bonding
Two atoms can share more than one pair of electrons to gain a filled shell
(very common in organic molecules)
2 C 2 H H C C H H C C H triple bond:
3 pairs of electrons
H C C C C N N N O O F
2. Formal Charge
Not all atoms are neutral in a Lewis or Kekule structure
Formal charges help chemists to keep track of the placement of electrons in molecules
Does not indicate that all of the charge is actually localized on one atom
H H
C: F.C. = 4 0 4 = 0
H C O O: F.C. = 6 2 3 = +1
H H
Oxygen is charged. H H
H C O H3C OH2
H H
C C C N N N O O O
not common
C C C N N O
Brevetoxin A (!!)
Assume carbon atoms are at ends of lines and where they meet
Assume enough CH bonds to give each carbon atom four bonds (an octet)
lines H
H
CH4 109.5 dash
C
methane H H
H H H wedge
H
lines: in the plane of the paper
dashes: going back into the paper (away from you)
wedges: coming out of the paper (toward you)
OH OH
H H
H H OH OH
H H
H H
Representing Molecules
Chemists use arrows to represent the motion of electrons within and between molecules.
1. The tail starts at the electrons that are moving (lone pair or bond).
2. The head shows where the electrons end up (lone pair or bond).
(l.p. to bond)
(bond to l.p.)
H
Boron atom is electrophilic (electron-loving).
B
H H
electrophile: electron-poor atom with a low-lying vacant or
6 electrons
easily vacated orbital; wants to accept electrons from a
(wants 2 more)
nucleophile
Formal Charge: N: 5 0 4 = +1
B: 3 0 4 = 1
These structures, called resonance structures, are not real or detectable, but they are a
useful conceptual tool for understanding the reactivity of molecules.
e.g. How can you predict where a nucleophile (such as H2N) will react
with formaldehyde (CH2O)?
O
H2N ?
H H
O O O
H H H H H + H
major minor
The minor resonance structure suggests that the carbon atom is
electron-deficient (electrophilic).
1. Only electrons move! Nuclei and the sigma- (single bond-) framework are
unchanged (Resonance occurs in the pi-system: conjugated lone pairs and pi-bonds).
structures.
6. Lower energy resonance structures contribute most to the overall structure of the
molecule.
10
i) Filled Octets: Second row elements (C, N, O , F) want an octet (filled valence
shell of electrons). Because C is the least electronegative, structures in which C has
6 electrons, 3 bonds and a positive charge are possible (not possible with N, O, F).
N N N
H3C C H3C C H3C C
O O O
A B C
N N
H3C C H3C C
O O
D E
A: follows guidelines
B: violates iii: 2 formal charges
C: violates ii & iii: negative charge on C; 2 formal charges
D: violates i & iii: 6 electrons on C; 2 formal charges
E: violates i & iii: 6 electrons on C; 2 formal charges
minor
11
OH O O O O
H+
pKa 10
phenol
OH O
H+
pKa 17
cyclohexanol
In general, the more resonance structures there are, the greater the stabilization.
1.397
12
Outline
III. Review of Molecular Orbital Theory (Read Chapter 2)
A. Atomic Orbitals (2-1)
B. Sigma-Bonding (2-2A)
C. Pi-Bonding (2-2B)
D. VSEPR Theory (2-4)
IV. Hybridization/LCAO
A. sp Hybridization (2-4A)
B. sp2 Hybridization (2-4B)
C. sp3 Hybridization (2-4C)
1. Rotation of Ethane versus Ethylene (2-3,7,8)
Problem Set #1 Due Today by 4pm
Problem Set #2 Posted: Due Tuesday (2/18/03)
1
A. Atomic Orbitals
The s- and p-orbitals are the most important in organic compounds.
Orbital pictures are actually electron probability clouds.
y y y y
x x x x
z z z z
s pX pY pZ
p-orbitals: two lobes with opposite signs, electrons further from nucleus
)
B. Sigma-Bonding (
Sigma-bonding orbitals are cylindrically symmetrical molecular orbitals.
Electron density is centered along the axis of the bond.
Single bonds are sigma-bonds.
e.g. H2 is the simplest sigma-bond
node
bonding: (+/+ or /) electron
* (anti-bonding) density centered between
nuclei
2
Sigma bonds aren't necessarily between two s-orbitals.
s+p p+p
node node
* *
pX pX pX
s
)
C. Pi-Bonding (
Pi-bonding orbitals are not cylindrically symmetrical.
Electron density is located above and below the axis of the bond.
Double and triple bonds are pi-bonds.
Double bond = +
node
H H
e.g. Ethylene
* H H
H C C H H C C H
H H H H
pY pY
H C C H or H C C H
H H H H
to simplify drawing of orbitals
3
Orbital Overlap
Orbitals must have the correct symmetry to overlap.
Orthogonal orbitals do not overlap.
Good Overlap Orthogonal: No Overlap
s s
s
pY
s px
s pz
px px
px
pY
px pz
pY pY
pz pz pY pz
If all bonding occurred between simple s- and p-orbitals, then all bond
angles would be approximately 90.
Most bond angles in organic molecules are ~109, ~120 and ~180.
~180
H
H
H
~109 H ~120
H
4
Simply...
Di-substituted Tri-substituted Tetra-substituted
linear (180) trigonal planar (120) tetrahedral (109)
Y Y
Y X Y X X Y
Y Y Y Y
180 121.7
H H
109.5 H
H C C H 116.6 C C C H
H H H H
HYBRIDIZATION!
Linus Pauling's Journals: http://osulibrary.orst.edu/specialcollections/rnb/
Why?
Hybrid orbitals are more directional, so they have more effective bonding
interactions.
Second row elements hybridize using their s- and p-orbitals (sp, sp2, sp3).
5
A. sp Hybridization (Linear)
s p 2 sp
two sp-orbitals
180
enhanced e density
in bonding regions
pZ
sp 2 sp-orbitals
X 2 p-orbitals
sp
e.g. Acetylene H C C H
2 H C H C C H
6
B. sp2 Hybridization (Trigonal Planar)
s 2p 3 sp2
109
X
s 3p 4 sp3
C H N H
H H H H
7
Assigning Hybridization to Atoms in a Molecule
(You need to be able to do this!)
H3C C N
a b H
8
Handout #3, 5.12 Spring 2003, 2/12/03
A. Bond Lengths: mostly dependent on atomic size, bond order, and hybridization
Bond Lengths ()
Multiple Bonding: Bond
3 3 3 3 length depends strongly on
sp sp C C 1.54 sp sp C O 1.42
bond order (length: single >
sp2sp2 C C 1.34 sp2sp2 C O 1.22 double > triple)
spsp C C 1.20
Bond Lengths ()
X X X. X.
Data taken from: Advanced Organic Chemistry, 3rd Edition, F. A. Carey and R. J. Sundberg
alkane-sp3
HCH3 48
CH3
alkene-sp2
HCH=CH2 44
CH=CH2
amine
HNH2 38 NH2
hydrogen
HH 35 H
alkyne-sp
HCCH 25 CCH
alcohol
HOCR3 17 OCR3
water
HOH 15.7 OH
thiol
HSR 1011 SR
ammonium
H+NR3 1011 NR3
nitrile (cyanide)
HCN 9.2 CN
phenol
HOAr 811 OAr
carboxylic acid
HOC(O)R 45 OC(O)R
HF 3.17 F
increasing
acidity
yes mirror zero How many two or more mirror yes achiral
achiral plane? stereocenters? plane? (meso)
no no
no one no*
yes yes
chiral chiral
* If you can't find a mirror plane, it doesn't mean that there isn't one. Compare mirror images!
Tricks:
1. Taking the mirror image of a stereocenter switches R and S. This means that, if a molecule is
chiral, switching the R/S configuration of every stereocenter will give you the enantiomer.
2. Exchanging any two groups on a stereocenter switches R and S.
1 1 1 switch 2 switch 2
4 2 2 4 4 2 1 and 2 4 1 1 and 3 4 3
3 3 3 3 1
R S R S R
mirror
Fischer Projections
Useful for comparing stereoisomers with more than one stereocenter.
The Rules:
1. At every intersection, the vertical lines are pointed back (away from you) and the horizontal lines
are pointed up (toward you).
2. Draw the carbon backbone of a molecule as the vertical line with the most highly oxidized carbon
on top.
a) You can think of oxidation as how many bonds carbon has to oxygen. So the ranking goes as
follows: CO2H > (CHO or CRO) > CH2OH > CH3
3. It is legal to rotate Fischer projections by 180 in the plane of the paper.
4. It is not legal to rotate Fischer projections by 90 or out of the plane of the paper.
1 1 1
2 4 2 4
3 4
3 3 2
1 3 1 2 1 switch 1
rotate rotate
2 4 4 2 2 4 3 1 2 4 4 2
180 90 horizontal
3 1 3 4 3 groups 3
Tricks:
1. Exchanging the horizontal substituents on a stereocenter switches R and S.
2. To take the mirror image, just exchange the horizontal substituents at each intersection. If the
molecule is chiral, this will give you the enantiomer.
3. If you can draw a mirror plane through the Fischer projection, then the molecule is achiral.
an atom:
an atom with four different groups attached is a stereocenter
stereocenters are also called chirality centers, asymmetric centers, and stereogenic centers
absolute configuration of a stereocenter is assigned using R/S nomenclature
a molecule:
achiral or chiral (optically active)
achiral molecules that contain stereocenters are called meso compounds
optically active molecules can be labelled (+/) or (d/l)
related molecules:
enantiomers (non-identical mirror images)
diastereomers (any stereoisomers that are not enantiomers)
geometric isomers (a specific type of diastereomer)
samples of molecules:
optically pure (only one enantiomer present in sample)
racemate or racemic mixture (mixture containing equal amounts of each enantiomer)
racemic mixtures are not optically active
mixtures in between optically pure and racemic are described by their optical purity or
enantiomeric excess (see section 5-7 in Wade)
Note: It is important not to confuse experimentally derived labels (+/ or d/l) with
structurally derived labels (R/S). They are not related!
Outline
H heat () or H
H C H Cl Cl H C Cl H Cl
H light (hv) H
H Cl Cl
or hv or hv etc.
H C Cl H C Cl H Cl Cl C Cl H Cl
Cl Cl Cl Cl
H H H
1
1. Mechanism of Radical Chlorination of Methane
(Free-Radical Chain Reaction)
termination step: side-reactions that slow the reaction; usually combination of two
reactive intermediates into one stable molecule
Initiation Step: Cl2 absorbs energy and the bond is homolytically cleaved.
or hv
Cl Cl Cl Cl Cl Cl
chlorine radicals
radical: species with an unpaired electron (usually just draw the unpaired electron)
2
Propagation Steps: The Meat of the Reaction
H H
a) Cl H C H C H Cl
H H
H methyl
radical
H Cl
b) C Cl Cl H C H Cl keeps the
H H chain going
methyl H
radical
Sum: H Cl
H C H Cl Cl H C H H Cl
H H
Cl Cl Cl Cl
H Cl
C Cl H C H
H H
H
H H H H
C C H C C H
H H H H
H H
Termination steps slow down and eventually stop the chain reaction.
3
B. Thermodynamics: energy changes that accompany chemical and physical
transformations
Thermodynamics are used to describe systems that are in their equilibrium state
A B
[products] [B]
Equilibrium Constant: Keq = =
[reactants] [A]
In the Gibbs Free Energy equation, the enthalpy term (H) is generally much larger
than the entropy term (TS). In other words, the change in enthalpy (bond
breaking/bond formation) usually governs the favorability of a reaction.
4
Standard Gibbs Free Energy: G = G at 298K and 1 atm
The 1.4 Rule: At 25 C (298 K), every 1.4 kcal/mol change in G results in a
factor of 10 difference in Keq (useful for estimating conversion of a reaction).
[A] [B]
reaction rate: how fast products appear and reactants disappear (measured
experimentally)
5
The rate constant is dependent on the activation energy and the temperature.
A = Arrhenius prefactor
In this class, we'll also refer to the activation energy of a reaction in terms of
G (free energy of activation).
D. Reaction-Energy Diagrams
A reaction-energy diagram is a plot of the potential energy as reactants are
converted to products (also called a reaction-coordinate diagram); very useful
for understanding thermodynamics and kinetics!
(or G)
The transition state
is state of highest
energy between
reactants reactants and products.
H
(or G) Transition states are
transient (written in
brackets).
6
If more than one product is formed in a reaction, what determines the
ratio of products? It depends on the reaction!
Thermodynamic Control: When the reaction is reversible (reactants and products are
in equilibrium), the reaction is said to be under thermodynamic control, and the
product ratio is determined by the relative energies of the products.
[TS B] transition B
[TS C] state B
A
potential energy
transition C
state C
B +4.2 1 : 1000
GBC +2.8 1 : 100
C +1.4 1 : 10
Kinetic Control: When the products are formed irreversibly, the reaction is said to be
under kinetic control, and the product ratio is determined by the difference in the
activation energies (the difference in the energies of the transition states (G)).
transition B
state B
[TS B]
[TS C] A
transition
potential energy
C
G state C
G product ratio
( G B G C) ([B] : [C])
A +4.2 1 : 1000
+2.8 1 : 100
B
+1.4 1 : 10
C
0 1:1
reaction coordinate
[A] [B] [C]
7
Is there any way to estimate the relative energies of transition states?
Hammond Postulate: Related species that are similar in energy are similar in structure.
The structure of a transition state resembles the structure of the closest stable species.
Endothermic reactions have
close in late transition states.
energy and
potential energy
structure
products In an endothermic reaction,
the transition state is product-
like (close in energy and
G > 0 structure to the product).
In an endothermic reaction,
anything that changes the energy
reactants of the product will also change
the energy of the transition state.
reaction coordinate
Exothermic reactions have
close in early transition states.
energy and
potential energy
structure
reactants In an exothermic reaction, the
transition state is reactant-like
(close in energy and structure to
G < 0 the reactant).
In an exothermic reaction,
anything that changes the energy
products of the reactant will also change the
energy of the transition state.
reaction coordinate
This will come in very handy when we start thinking about radical halogenation reactions!
8
Multi-step reactions have more than one transition state.
The rate-determining
product step is the step with the
highest energy transition
reaction coordinate state.
initiation step:
or hv
Cl Cl Cl Cl H = BDE = 58 kcal/mol
9
It is important that the initiation step involves cleavage of a fairly weak
bond like ClCl.
Other than that, the initiation step is not important in the overall
thermodynamics and kinetics of the reaction. This is because one
initiation step starts a chain that can go through thousands of
propagation cycles.
Propagation Steps:
H H
1) Cl H C H C H Cl
H H
H
break H3CH: H = +104 kcal/mol
step 1: H1 = +1 kcal/mol
H Cl
2) C Cl Cl H C H Cl
H H
methyl H
radical
break ClCl: H = +58 kcal/mol
step 2: H2 = 26 kcal/mol
10
Drawing the Reaction-Energy Diagram:
Ea2
H1 CH3 + Cl2 Experimental Values:
CH4 + Cl (cannot predict)
Ea1 = +4 kcal/mol
Ea2 = +1 kcal/mol
Hoverall H2
11
Chemistry 5.12 Spring 2003, 3/7/03
Handout #8: Lecture 12
Outline
Cl
or hv Cl
Cl Cl
40% 60%
(1) (2)
Propane has two inequivalent types of hydrogens that can be abstracted in the
first propagation step.
The first propagation step determines which product will be formed (1 or 2).
H H H H
Cl H Cl
H H H H H H H
1 radical
H H H
Cl H Cl
Me Me Me Me
2 radical
Primary (1) Carbon: carbon that has only one other carbon attached to it
Secondary (2) Carbon: carbon that has two other carbons attached to it
Tertiary (3) Carbon: carbon that has three other carbons attached to it
H R R
R C H R C H R C H
1 2 3
H H R
Me
Br
Me Br Me
Me Me
Me
Me Me Br
Br
sec-butyl bromide (2) tert-butyl bromide (3)
2. Relative Reactivity
2
H H H H Cl H
H H or hv Cl H H H
Cl Cl
H H H H H H H H H H H H
1 1
1 chloride (40%) 2 chloride (60%)
Why?
Primary:
H H H H form HCl: 103 kcal/mol
H H Cl H H H Cl break 1 CH: +98 kcal/mol
H H H H H H H overall: H = 5 kcal/mol
1 radical
Secondary:
H H H
form HCl: 103 kcal/mol
H H Cl H H H Cl break 2 CH: +95 kcal/mol
H H H H H H H H overall: H = 8 kcal/mol
2 radical
Ea 1 kcal/mol
potential energy
1 Ea
2 Ea
Cl
1 radical + HCl
H = 3 kcal/mol
2 radical + HCl
reaction coordinate
This reaction is under kinetic control, so the product ratio is determined by Ea.
How can you predict the value of Ea?
The energy of a transition state will always depend, to differing extents, on the energies of
the reactants and the products.
In this case, the reactants are the same for both processes (same energy).
The only energy difference is in the products: the 2 radical is lower in energy than the 1
radical.
This means that the transition state leading to formation of the 2 radical is slightly lower in
energy than the transition state leading to formation of the 1 radical.
Br
or hv Br
Br Br
3% 97%
Cl
or hv Cl
Cl Cl
40% 60%
Radical brominations are generally much more selctive than radical halogenations.
Secondary:
H H H
form HBr: 88 kcal/mol
H H Br H H H Br break 2 CH: +95 kcal/mol
H H H H H H H H overall: H = +7 kcal/mol
2 radical
The HBr bond (BDE = 88 kcal/mol) is much weaker than the HCl bond (BDE = 103
kcal/mol).
Ea > 2 kcal/mol
1 radical + HBr
potential energy
H = 3 kcal/mol
2 radical + HBr
Br
reaction coordinate
This diagram looks slightly similar to the one we drew for the chlorination of propane.
In an exothermic reaction, the transition state more closely resembles the reactants.
In an endothermic reaction, the transition state more closely resembles the products.
The 3 kcal/mol energy difference between the 1 and 2 radicals will have the biggest
effect on the transition state energies in the endothermic abstraction with bromine.
This is why radical brominations are more selective than radical chlorinations!
potential energy
H = 3 kcal/mol
Cl 2 radical + HBr
1 radical + HCl
H = 3 kcal/mol
2 radical + HCl
Br
reaction coordinate reaction coordinate
exothermic endothermic
(more selective)
G. RADICAL STABILITY!
Why is it easier to break a 2 CH bond than a 1 CH bond?
It's easier to homolytically cleave a bond when more stable radicals are formed.
Radical Stability:
R H H H
> > >
R R R R R H H H
Tertiary (3) > Secondary (2) > Primary (1) > Methyl
p
R
R
R
sp2
Alkyl groups stabilize electron-deficient radicals by donating electron density in two ways:
induction and hyperconjugation.
CH3
H3C CH3
R H
H
p
H H
H H H H BDE = 98 kcal/mol
H H H H H H H
propane
H H H
H H H H H H BDE = 87 kcal/mol
H H H H H H H
propene allylic radical
H H H
H H
H H H
H
toluene
H H
BDE = 85 kcal/mol H H
benzylic radical
10
H H
H BDE
OKAY: These hydrogens act like
2 96 kcal/mol regular 2 hydrogens.
H H
H H
H H H
HH HH
hv
N Br N H
NBS
O Br O
H Br
O OH OH
Br
N Br N Br Br Br N
released
O O slowly O
11
SN2 SN1
Mechanism: Concerted Two Steps
(Look for carbocation rearrangements.)
E2 E1
Mechanism: Concerted Two Steps
(Look for carbocation rearrangements.)
1
Generic Reaction-Energy Diagrams
Substitution Elimination
X
R RR
+
Nuc X
H RR
R R
B
energy
energy
R
R X
X B
Nuc R
R
R R
R Nuc R
R B H
X
R
energy
Nuc R
B
R
X B
R X R
R
Nuc R R
R
R B H
R Nuc
X R
reaction coordinate (SN1) reaction coordinate (E1)
Bimolecular yes no
Is Nuc/Base strong? What kind of substrate?
Reaction
1
2, 3, or
stabilized 1
Unfavorable
Is Nuc/Base bulky? Reaction
yes
Unimolecular
Reaction
no E2
3
yes
What kind of substrate? mostly E1* Is Nuc/Base bulky?
2
methyl or 1 SN2 + E2 no
* Under conditions that favor a unimolecular reaction (weak nuc/base and polar protic solvent),
mixtures of SN1 and E1 are usually obtained.