CHM 233

Dr. Stephanopoulos

Final Study Guide

November 30, 2016

Table of Contents (Chronological order)

Chapter
Chapter
Chapter
Chapter
Chapter
Chapter
Chapter
Chapter
Chapter
Chapter
Chapter
Chapter

1: Review of General Chemistry 3

2: Molecular Representations
5
4: Alkane Structure and Nomenclature
11
15: Infrared spectroscopy, Mass spectroscopy
16: Nuclear Magnetic Resonance
16
3: Acids and Bases
17
5: Stereoisomerism 20
6: Chemical reactivity and Mechanism
22
7: Substitution Reactions 25
8: Alkenes and Elimination Reactions 30
9: Addition Reactions of Alkenes 39
11: Radical Reactions 43

14

Chapter 1: Review of general chemistry (Lectures

1,2,start of 3)
1. Lewis dot structures
a. Chemical symbols where the valence electrons are
represented as dots or solid lines
b. Each side of an atom must have one dot before doubling
up.

2. Formal Charge
a. Formal charge = #valence electrons (# non bonding
electrons+1/2 of bonding electrons)

3. Covalent bonds (polar, nonpolar)

a. Based on electronegativity
i. Electronegativity is a measure of the ability of an
atom to attract electrons
b. If the difference in electronegativity is less than 0.5, the
elctrons are considered to be equally shared between the
atoms.
i. Between .5 and 1.7 is a polar covalent bond
ii. Larger than 1.7 is not shared at all

4. VSEPR Theory
a. Valence shell electron pair repulsion VSEPR theory
3

b. This is literally memorizing how the number of bonds vs

lone pairs affect the geometry of an atom

5. Dipole moment and bond polarity

a. Electronegativity differences cause induction
b. Induction results in a dipole moment, because the
electrons are shifting within their orbitals
c. Dipole moments tell us how polar a bond is
d. ionic =ed ; e=electron charge ; d=bond length
e. Ionic character = (actual dipole)/(dipole for ionic bond)
6. Intermolecular forces
a. Attractions between molecule, 3 main types;
i. Dipole dipole interactions
1. Results when polar molecules line up their
opposite charges.
2. In terms of strength, it is weaker than
Hydrogen bonding but stronger than dispersion
forces in small molecules

ii. Hydrogen bonding

1. Only occurs when a hydrogen shares electrons
with a highly electronegative atom (O,N,F).
a. The hydrogen carries a large partial
charge
2. Technically a specific type of dipole-dipole
bonding

iii. Dispersion Forces

1. The constant random motion of the elctrons in
the molecule will sometimes produce an
electron distribution that is not evenly
balanced with the positive charge of the nuclei
2. The greater surface area of a molecule, the
more temporary dipole attractions are possible
a. Explains why more branched molecules
have lower boiling points.

Chapter 2: Molecular representations (Lectures

3,4)
1. Bond-line structures
a. Lines are drawn between atoms to show covalent bonds
b. Atoms are bonded at angles that represent the geometry of the
bond angles
c. Carbon atoms are not labeled, but a carbon is assumed to be at
every corner or endpoint on the zigzag
d. Carbon-Hydrogen bonds are omitted
e. Atoms other than C or H should be labeled with all hydrogen
atoms and lone pairs attached
f. Lone pairs can be omitted, but formal charges must be specified
2. Functional groups
a. Memorization

3. Formal charges
a. Memorization

4. 3D bond-line structures (dash/wedges)

a. Dash: coming out of page
b. Wedge: Going into page
c. line: bond is in plane of page

5. Resonance structures
a. Occurs with delocalized systems.
b. The delocalization of electrons increase stability
i. Minimize electron repulsion
ii. Interact with more nuclei
6. Rules/Patterns for resonance structures
a. Curved arrows show movement of electron pair
i. Arrow starts where the electrons currently are
ii. Arrow ends where electrons are going
iii. Does not show movement of atoms
b. Avoid breaking single bonds with arrows
8

c. Single bonds break but not with resonance

d. Resonance -> overlapping p orbitals; single bonds -> sigma
bonds
e. Never exceed an octet for 2nd row elements
i. Cannot hold more than 8 electrons in the 2nd energy level
(2s, 2p)
1. Nowhere to put extra electrons from arrow
f. Total charge must be conserved in structures

g. 5 Main bonding patterns in which resonance occurs

i. Allylic lone pairs
1. Remember to conserve charge

ii. Allylic positive charge

1. Only one arrow
2. Formal charge is shuttled to different atoms in
molecule
9

iii. Lone pair of electrons adjacent to a positive charge

1. Only one arrow is necessary
2. Not always possible to cancel out charges
3. Nitro group: N already has 4 bonds, so have to push
one bond to make room for incoming electrons

iv. A pi bond between two atoms with different

electronegativity
1. Pi electrons are attracted to the more electronegative
atom
2. Overall structure is weighted average of two
resonance structures
3. Helps understand bond polarity

10

v. Conjugated pi bonds in a ring

1. Each atom must have unhybridized p orbitals that
can overlap
2. Can draw electrons moving clockwise or
counterclockwise
3. No actual motion, structure is average of resonance
structures

vi. Summary

h. Other rules regarding resonance structures

i. Rule 1: Minimize charges
1. Ideally: no charges
2. Charges are okay, but >2 is rare
3. Formal charge generally decreases stability,
especially:
a. +1 charge on electronegative charge
b. -1 charge on low electronegativity charge

11

ii. Rule 2: Electronegative atoms can have a +1 charge but

only if they have an octet
1. Electronegative atom donates electrons to help
neighbor get an octet
2. electrons delocalize between two atoms
iii. Adjacent Carbons with opposite charge: bad
1. Will prefer to form a bond
2. No good driving force for separating charges (both
atoms have same electronegativity)

Chapter 4: Alkane structure and nomenclature

(Lectures 5,6,7)
1. Alkane naming (IUPAC system)
a. IUPAC Naming system
i. Find the parent chain
1. Longest consecutive chain of carbons
2. If two chains exist with same # of carbons, choose
the one with more substituents
3. Once you find the longest carbon chain, name it
4. If a parent is a ring, add the term cyclo- to the alkane
name
a. Rings are often treated as the parent if they
have more carbons than substituents, however
parent chains cannot contain carbons both in
and out of the right
ii. Identify substituents
1. Some substituents have common names that are
used more often than the IUPAC names
iii. Putting the name together
1. Number the carbons in the parent chain
2. If one substituent present, number carbons such that
the substituent has the lowest possible number.
3. With multiple substituents, choose the numbering
scheme that gives the first substituent the lowest
possible number
4. In the case of a tie, choose the numbering scheme
that gives the second substituent the lowest possible
number
5. To assemble the complete name, assign a locant to
each substituent, and list them before the parent
chain name in alphabetical order.
a. A prefix is used if multiple substituents are
identical.
b. Prefixes are not used for alphabetical purposes
(except iso)
12

iv. Naming bicyclic compounds

1. To name a bicyclic compound, include the prefix
bicycle in front of the normal name ending in ane.
2. Label the number of carbons in each bridge,
3. To number the bicycle parent chain, start at a
bridgehead connector first, and number the longest
path first
4. Without violating above rules, give the substituents
the lowest numbers possible

13

2. Constitutional isomers
a. Same molecular formula, different arrangement/connectivity of
atoms
b. Two ways to determine if two molecules are constitutional
isomers
i. See if you can rotate/flip one into the other
ii. Name them! Same name -> same compound

3. Stability of alkanes
a. Stability can be compared by burning the molecules
i. Higher energy -> more stable
ii. change in enthalpy is the heat given off in combustion
4. Conformational analysis of alkanes
a. Newman projections
i. Look directly down the C-C single bond
ii. Front carbon eclipses the back carbon
1. Front carbon is a point
2. Back carbon is a circle
iii. Draw the substituents at 120 degrees from each other
iv. Dihedral angle
1. Angle between Hs on adjacent carbons
2. Different dihedral angles have different stabilities
a. Due to repulsion of electrons in the bonds

14

5. Cycloalkanes
a. cycloalkanes adopt non-flat conformations
b. cyclohexane is the most stable in the chair configuration
c. Other conformations exist but arent as stable such as the boat
or the half chair
6. Substituted cyclohexane conformations
a. Monosubstituted cyclohexane
i. Vast majority of cyclohexane -> chair
ii. When it has enough energy, it flips
iii. Larger substituents prefer to be equatorial
b. Disubstistuted cycloalkane
i. Cis when there are two groups on same side of ring
ii. Trans when two substituents are on opposite sides of a ring

iii. Not constitutional isomers, stereoisomers

Chapter 15: Infrared Spectroscopy, mass

spectrometry (Lectures 7,8)
1. Introduction/Principles of spectroscopy
a. Tells us different properties of a molecule
b. Interaction of light with matter
c. IR energy absorbed depends on the type of bond
d. Three key parameters
i. Wavenumber
1. Where it absorbs
ii. Intensity
1. How much it absorbs
iii. Shape
15

2.

3.

4.
5.

6.

7.

1. Sharp or broad
Wavenumber, intensity, shape of IR spectra
a. Wavenumber
i. Depends on bond strength and masses of atoms bonded
together
ii. We generally only care about the region above 1500 cm-1
iii. Hybridization affects IR vibration
1. Shorter/Stronger bond has a higher wavenumber
iv. Resonance in C=O weakens bond, lowers wavenumber
b. Intensity
i. Depends on bond dipole moment
ii. Completely symmetrical alkene would not give a C=C
signal
iii. Also depends on number of bonds of a given type
c. Shape
i. Depends on the homogeneity of bond
1. More homogeneous -> sharper peak
ii. Mostly important for alcohol signals
1. In a more dilute solution, alcohol bonds are sharper.
iii. Peak shape also due to coupling with bending modes
IR determination of functional groups
a. 1600-1850 cm-1 check for double bonds
b. 2100-2300 cm-1 check for triple bonds
c. 2700-4000 cm-1 check for X-H bonds
d. Analyze wavenumber, intensity, and shape
e. Chart given is on blackboard
Principles of mass spectrometry
a. Measuring the mass of a molecule
b. Compound is vaporized then ionized, and its mass detected
Isotope peaks (M+,(M+1)+,(M+2)+)
a. If (M)+ peak gives odd mass -> odd number of Ns in molecule
and vice versa
b. Isotopes can give you an (M+1)+ peak
c. Chlorine indicates a 33% intensity of (M)+ peak in the (M+2)
peak
d. Bromine indicates a equal (M)+ and (M+2)+ intensity
Fragmentation of alkanes
a. smaller peaks in each group -> loss of H radicals
b. for branched alkanes -> cation forms that has the most number
of substituents
Hydrogen deficiency index and degrees of unsaturation
a. Each degree of unsaturation reduces number of hydrogens by 2
b. Each multiple bond: one degree of unsaturation
c. Each ring: one degree of unsaturation
d. HDI: total degrees of unsaturation
i. HDI = .5(2C+2+N-H-X)
16

Chapter 16: Nuclear Magnetic Resonance (Lectures

9, 10)
1. General principles of NMR
a. Protons and neutrons in a nucleus behave as if they are spinning.
b. If the total number of neutrons and protons is an odd number,
the atoms will have net nuclear spin
c. The spinning charge in the nucleus -> Magnetic moment
i. Magnetic moment creates a magnetic field
ii. This field can align with an external magnetic field
d. The stronger the magnetic field the larger the energy gap
e. The magnetic moment of the electrons generally reduces the
effect of the external field
2. Characteristics of NMR spectra
a. Number of signals
b. Signal location
c. Signal area
d. Signal Shape
3. Equivalent/nonequivalent protons
a. Homotopic protons
i. Can rotate onto eachother without changing the molecule
b. Entantiotopic
i. Have a plane of reflection that makes one the mirror image
of the other
c. If not homotopic or entatiotopic then they are not equivalent
protons
4. Chemical shifts
a. Higher energy protons are downfield while lower energy protons
are upfield
b. Protons are shifted downfield when electronegative atoms cause
deshielding

17

c. Table 16.1 can be used to adjust ppm depending on proximity to

functional groups
5. Integration and multiplicity
a. Integration
i. Area under the peak quantifies the relative number of
protons that give rise to a signal

b. Multiplicity
i. Occurs when there are protons two or three bonds away
that are in different environments
ii. Splitting rules
1. Equivalent protons do not split each other
2. To split, protons must be within a 2 or 3 bond
distance
3. The n+1 rule only applies to protons that are all
equivalent

6.

13

C NMR (Number of Peaks)

a. Number of peaks represents how many chemically distict
carbons there are
18

Chapter 3: Acids and Bases (Lectures 11,12)

1. Bronsted-Lowry definitions
a. Acids donate a proton
i. Results in a conjugate base
b. Bases accept a proton
i. Results in a conjugate acid

2. Curved arrows in mechanisms

a. Curved arrows are used to show when bonds break and form,
when pairs of electrons move
b. Different from resonance arrows since the electrons move.
c. Charge is conserved

3. Quantitative analysis of acidity (pKa)

19

a. Smaller pKa indicates a stronger acid

b. Very big indicates a weak acid
c. To compare, subtract the left pKa value from the right. The value
is a log value

4. Qualitative analysis of acidity (ARIO)

a. The type of atom that carries the charge
i. More electronegative atoms are better at stabilizing charge
b. Resonance
i. Resonance greatly stabilizes a formal negative charge
c. Induction
i. Induction stabilizes a negative charge by spreading it out
d. The type of orbital where the charge resides
i. The type of orbital also can affect the stability of a charge
1. Negative charges are more stable closer with less
hybridized orbitals
e. Exceptions to ARIO

5. Position of acid/base equilibria

20

6. Lewis acid/base definitions

a. Lewis acid accepts and shares an electron pair
b. Lewis base donates and shares an electron pair
c. All bronsted-lowry acids/bases are also lewis acids/bases
i. But the vice versa is not true

Chapter 5: Stereoisomerism (Lectures 13,14)

1. Cis/trans double bonds and ring substituents
a. cis
i. On same side of a double bond
b. trans
i. On opposite sides of a double bond

21

c. Must have same group for cis/trans notation

2. Chirality
a. Four unique substituents bonded to a carbon
b. Not identical to its mirror image

3. Symmetry considerations in chirality

a. If a chirality center can be superimposed onto itself, it is not a
chirality center
4. Cahn-Ingold-Prelog rules
a. Using atomic numbers, prioritize the four groups attached to the
chirality center
b. Arrange the molecule in space so the lowest priority group is
away from you
c. Count the group priorities 1..2..3 to determine whether the order
progresses in a clockwise of counterclockwise direction
i. If there is a tie, move on to the next group of atoms to
figure out which is higher priority.
1. Double bonds count as two single bonds
2. Triple bonds count as three single bonds
d. Clockwise = R and Counterclockwise = S

22

5. Optical activity
a. The degree to which light is rotated depends on the sample
concentration and the path-length of the light
|observed |
100
b. %ee=
| of pure entantiomer|

6. Categories of isomers (enantiomers, diasteremers, meso)

a. Enantiomers
i. Mirror Image
b. Distereomers
i. Not Mirror Image
c. If a molecule has an internal mirror plane, then it is achiral.
i. Half the molecule reflects the other half, canceling out
optical activity
ii. Molecules with an even number of chirality centers and a
mirror plane are considered meso compounds.
iii. Meso compounds have less than the predicted 2N isomers

23

Chapter 6: Chemical reactivity and Mechanism

(Lectures 15,16)
1. Enthalpy, entropy, Gibbs free energy
a. Enthalpy
i. Heat energy exchange between reaction and its
surroundings at constant pressure
ii. Breaking a bond requires the system to absorb energy
iii. Bonds can break homolytically or heterolytically

iv. dH is negative for exothermic reactions

v. dH is positive for endothermic reactions

b. Entropy
i. Measure of the randomness of a system

24

2.
3.

4.

5.

ii. Number of states that a molecules energy can be

distributed over
iii. Three possible types of energy
1. Vibrational
2. Rotational
3. Translational
c. Gibbs Free Energy
i. dG<0 is a spontaneous reaction
ii. dG>0 not spontaneous reaction
1. requires more energy from outside sources
iii. dG = dH-TdS
iv. Side with lower dG is favored for equilibrium
Bond dissociation energy
a. Direct measure of bond strength
b. Breaking a bond requires the system to absorb energy
Equilibrium (relation with dG)
a. The greater the magnitude of dG in an exothermic process, the
more the equilibrium will favor the products
b. Equilibrium is the state with the lowest free energy
Kinetics and rate equations
a. Governed by the rate of molecular collisions
b. 5 factors affect the reaction rate
i. Concentration of reactants
1. As concentration increases, so will the rate
ii. Activation energy
1. Lower Ea means faster rate
iii. Temperature
1. Increasing T increases rate
iv. Geometry and sterics
v. Presence of a catalyst
1. Catalyst increases the rate
c. Rate = k[reactants]
Transition states vs intermediates
a. Transition state occurs at a maximum of dG
i. It cannot be captured or observed directly
b. Intermediates occur at local energy minumums of dG

25

6. Nucleophiles vs electrophiles
a. Nucleophiles love to attack a nucleus
b. Electrophileslove to accept electrons
i. Another name for lewis acid
7. Arrow pushing (four key mechanisms)
a. Nucleophilic attack

b. Loss of a leaving group

c. Proton transfer

26

d. Rearrangements

8. Carbocation rearrangements
a. Carbocations will rearrange to become more stable, and will do
so before a reaction with a nucleophile. The two common types
are shown above

Chapter 7: Substitution reactions (Lectures 17)

1. General principles of substitution reactions
a. One group attacks, and one group leaves
b. Leaving group always takes a pair of electrons with it
c. Criteria for encouraging substitution
i. Electronegative group creates a partial charge to attract
nucleophile
27

ii. Leaving group stabilizes the electrons it leaves with

2. Alkyl halide nomenclature
a. Very similar to alkane naming (IUPAC, chapter 4)
i. Identify and name the parent
ii. Identify and name the substituents
1. Halogens are treated as substituents and receive
names such as fluoro-, chloro-, bromo-, and iodo-.
iii. Number the parent chain and assign a number to each
substituent
iv. Assemble the substituents alphabetically

3. SN2 Mechanism
a. Rate = k[substrate][nucleophile]
b. SN2 is a concerted mechanism, which means that both steps
happen all in one step.
c. Stereospecificity of SN2 Reactions
i. Walden inversion occurs, aka a (S) chiral center
becomes a (R) chiral center
1. This is due to the SN2 process occurring through a
backside attack at the same time as the loss of a
leaving group
d. Structure of the Substrate
i. Methyl halides and primary alkyl halides react most
quickly with nucleophiles, while tertiary alkyl halides are
pretty much unreactive
1. This is due to the increasing amount of energy
required to overcome the activation energy barrier
4. SN1 Mechanism
a. Rate = k[substrate]
i. The rate determining step is the loss of a leaving group,
which is why the concentration nucleophile has no
effect on the rate of the reaction
b. Stereochemistry of SN1 Reactions
i. Since SN1 reactions are stepwise mechanisms, they can
either have a configuration inversion or a retention of
configuration, however there is a slight preference for
the inversion due to ion pairs
1. This produces a racemic mixture, which is 50/50
of both the (R) and (S) chiral centers
28

c. Steps of the SN1 mechanism

i. (optional) Proton transfer turns bad LG into good LG
(sometimes happens after the substitution process)
ii. Loss of a leaving group
iii. (optional) Rearrangement
1. Intermediate rearranged to more stable form,
almost always secondary to tertiary carbocation
iv. Nucleophilic attack
d. Structure of the substrate
i. The reactivity of SN1 is opposite of SN2
1. Methyl is least reactive, while tertiary
carbocations are the most reactive.
2. The potential energy required for the formation
tertiary carbocation is smaller than the potential
energy required for the formation of the
secondary carbocation

5. Hammond Postulate
a. Activation energy is affected by the relative stability of the
intermediate
i. Tertiary>Secondary>Primary>Methyl in terms of
carbocation stability
6. Energy diagrams for substitution reactions
a. Since SN2 occurs in one step, this is represented in the energy
diagram.
b. Since SN1 occurs in two steps, there are two steps on the
energy diagrams as seen above

29

7. Comparing SN2 vs. SN1

a. Four important factors
i. The substrate and stability of carbocations
1. SN2 occurs at a less stable carbocation. Primary
carbocations almost always go through SN2
2. SN1 occurs at more stable carbocations due to the
stepwise process. Tertiary carbocations almost
always go through SN1
3. Resonance stabilizes a carbocation, and makes it
more likely to be a SN1 mechanism.
a. Vinyllic and aryl halides are not stabilized by
resonance however.
b. They have one fewer carbon between
double bond and LG

ii. The strength of the nucleophile

1. Good nucleophiles favor SN2 since the SN1 reaction
does not depend on the nucleophile

30

a. Good nucleophiles have a negative charge

and polarizability, and the smaller a
nucleophile the better.

iii. The quality of the leaving group

1. Both mechanisms require a good electrophile
a. A good electrophile can stabilize a negative
charge through induction or resonance
b. Good electrophiles favor SN1
c. General rule: good leaving groups are
conjugate bases of strong acids.
i. Strong Acids:
1. HCl HI HBr HClO4 HNO3 H2SO4
ii. Their conjugate bases
1. Cl- I- Br- ClO4- NO3- SO4iii. Water is a great leaving group
iv. The solvent
1. To promote SN1 reactions, polar protic solvents can
be used to stabilize the nucleophile, and will allow
the leaving group to leave first by stabilizing the
nucleophile.
2. Polar aprotic solvents do not stabilize nucleophile,
while also lowering the activation energy

31

Chapter 8: Alkenes and Elimination Reactions

(Lectures 18,19)
1. General principles of elimination reactions
a. Elimination often happens in competition with substitution
b. Two main ingredients for substitution
i. Nucleophile and electrophile with a leaving group
ii. A base and an electrophile with a leaving group

32

2. Alkene nomenclature
a. Names using same procedure for alkanes, with little changes
i. Identify parent change, which should include the C=C
double bond
ii. Identify and name substituents
iii. Assign a locant (and prefix if necessary) to each
substituent. Give the C=C double bond the lowest
number possible
iv. List the numbered substituents before the parent name
in alphabetical order. Ignore prefixes (except iso) when
ordering alphabetically
v. The C=C double bond locant is placed either just before
the parent name or just before the ene suffix

3. Stability of alkenes
a. No rotation is allowed to keep the pi bond intact, which results
in the cis and trans forms being different.
b. For cyclic atoms with less than 8 atoms in the ring, only the
cis isomer is stable
33

i. Only cyclooctane is stable with trans

c. Cis and trans only apply when two identical groups on either
end on of the double bond
d. If there are two different groups, E and Z are used
i. AKA Entgegen or Zusamenn
ii. Assign priorities to groups attached to the C=C double
bond
iii. If the high priority groups are on the same side, we call
it Z (like zis) otherwise its E.
iv. Cis isomers are generally less stable than trans
4. The E2 Mechanism
a. Rate = k[base][substrate]
b. Tertiary substrates are unreactive towards SN2 but readily
react by E2

c. Tertiary>Secondary>Primary in terms of reactivity.

i. Activation energy of the tertiary substrate is lower

34

d. Regioselectivity of E2
i. If there are multiple reactive sites on a molecule,
multiple products are possible
ii. There are multiple places where a proton can be
removes
iii. Regioselectivity occurs when one constitutional product
is favored over another
iv. Zaitsev and Hofmann product
1. Zaitsev: More substituted carbon
a. Favored with an unhindered base
b. Thermodynamically favored
2. Hofmann: Less substituted carbon
a. Favored with a hindered base
b. kinetically favored
e. Stereoselectivity of E2
i. Both the transition state and product are more stable for
the trans product.
1. Can be described using the term anti-periplanar.
2. Even though the E isomer is more stable because
it is less sterically hindered, the requirement for
an anti-periplanar transition state can often lead
to the less stable Z isomer

35

5. The E1 Mechanism
a. Analogous to SN1
i. Loss of a leaving group
ii. Elimination through proton transfer
b. Rate = k[substrate] does not depend on the identity or
concentration of the base
i. Loss of the leaving group is the rate determining step
c. Tertiary>Secondary>Primary in terms of reactivity.
d. Energy diagrams for E1 are similar to the SN1 reaction energy
diagrams
e. Regioselectivity of E1
i. E1 reactions generally produce the Zaitsev product
f. Stereoselectivity of E1
i. No requirement for anti-periplanar because the leaving
group has already left

36

6. Energy diagrams for elimination reactions

a. E2 and E1 energy diagrams mirror the energy diagrams for
SN1 and SN2, however in E1 the Zaitsev product is usually at a
lower energy compared to the Hofmann product due to the
carbocation stability
7. Comparing E1, E2, SN1, and SN2
a. Elimination and substitution are always in competition,
sometimes there is one or the other, sometimes it is a mixture
of both mechanisms
b. Predicting the mechanism
i. Is the reagent more likely to be a base or a nucleophile
1. Kinetics control nucleophilicity
2. Thermodynamics control basicity
3. Strength of a nucleophile
a. The more negative a charge, the more
nucleophilic a molecule will be
b. The more polarizable a molecule, the better
a nucleophile it will be
i. Larger atoms are always more
polarizable
c. The less sterically-hindered a molecule is,
the better nucleophile it will be due to the
kinetic effect
4. Strength of a base
a. The strength of a base can be assessed
using the pKa of its conjugate acid. The
lower the pKa of the conjugate, the weaker
the base is.

37

b. If the base is neutral, assess the strength of

its conjugate acid using ARIO
i. A The type of atom that carries the
charge
1. More electronegative atoms are
better at stabilizing charge
ii. R - Resonance greatly stabilizes a
formal negative charge
iii. I - Induction stabilizes a negative
charge by spreading it out
iv. O - The type of orbital can affect the
stability of the charge
1. 2s<sp<sp2<sp3,p

c. reagents that act as nucleophiles only are

either highly polarizable and/or they have
very strong conjugate acids
d. Reagents that act as bases only have either
very low polarizability or are sterically
hindered
e. The stronger the reagent, the more likely it
is to promote SN2 or E2, while weaker
reagents promote E1 or SN1
f. More sterically hindered reagents are more
likely to promote elimination over
substitution
ii. Analyze the substrate and predict the mechanism

38

iii. Consider the relevant regiochemical and stereochemical

requirements.
39

c. Mechanism Hints
i. If a reaction requires heat it usually is SN1 or E1
ii. If a reaction requires acid, it is E1 or SN1
1. Cannot be E2 because E2 requires a good base
iii. If a reaction mentions a solvent, SN2 or SN1
1. Protic Solvents (H2O, CH3OH) favor SN1 by making
the nucleophile weaker
2. Aprotic solvents (DMSO, DMF) favor SN2 by
destabilizing the nucleophile and making it more
reactive.

40

Chapter 9: Addition reactions of alkene (Lectures

21,22)
1. Thermodynamics of addition reactions
a. Addition reactions are at equilibrium
i. H<0 S<0 -TS>0
ii. The signs for elimination are:
1. H>0 S<0 -TS<0
iii. Elimination is favored at higher Ts
2. Markovnikov vs anti-Markovnikov addition
a. Markovnikov addition
i. Halogen atoms tend to add to the more substituted carbon
ii. If a chiral center forms, a racemic mixture of markovnikov
products are formed
b. Anti-Markovnikov addition
i. Depends on mechanism. Opposite of Markovnikov addition
3. Hydrohalogenation
a. Addition of hydrogen and a halogen across a double bond
b. The halogen prefers to go to the more substituted carbon AKA
Markovnikov addition
c. Two step process
i. Proton Transfer
1. Proton transfer is the rate determining step
ii. (optional) rearrangement if a more stable carbocation can
be made
1. They follow same rules as E1 and SN1 reactions
iii. Nucleophilic attack

4. Hydration
a. Addition of water across a double bond
i. H- on one side, HO- on the other side
1. HO- will go to the more substituted carbon,
Markovnikov addition

41

ii. Rate of reaction can be controlled using Le Chateliers

principle
iii. Stereochemistry is controlled by geometry of the
carbocation, the introduction of a chiral center will result in
a racemic mixture.
iv. Three major steps
1. Proton Transfer
2. (optional) rearrangement if a stable cation can be
formed
3. Nucleophilic attack
4. Proton Transfer

5. Oxymercuration-demercuration
a. Just a hydration reaction that always gives the markovnikov
product
i. No possibility for rearrangement due to the lack of a
carbocation

b. The mercurinium ion is a good electrophile that can be easily

attacked by a weak nucleophile like water
6. Hydroboration-oxidation
a. Used if anti-Markovnikov hydration is wanted
b. Achieves syn addition, H- and OH- will always be on the same
side
i. Anti addition is not observed
c. When one or two chirality center is formed, a racemic mixture
will form

42

7. Catalytic hydrogenation
a. Addition of H2 across a C=C double bond
b. If a chirality center is formed, syn addition is observed
c. A catalyst is required to lower the activation energy so it can be
feasible at practical temperatures
i. Catalyst does not affect the spontaneity of the process
ii. Typical catalysts used include metals Pt,Pd,Ni

8. Halogenation
a. Addition of two halogen atoms across a C=C double bond
b. Halogenation occurs with anti addition

9. Halohydrin Formation

43

a. Halohydrins are formed when Br2 and Cl2 are added to an alkene
with water as the solvent
b. The reaction produces the anti addition of a halogen and OH
across a C=C double bond
c. The OH group adds to the more substituted carbon, because
water attacks the carbon that has the larger positive charge

10. Anti-dihydroxylation
a. Occurs when two OH bonds are added across a C=C double
bond
b. Is achieved through a multistep process

c.
11.
a.
b.

Anti product is yielded

Syn-dihydroxylation
OsO4 is used for syn-dihydroxylation
Like other syn additions, the first step adds across the double
bond in a single step
c. Can also be achieved with KMnO4

44

12. Oxidative cleavage with ozone

a. C=C bonds are reactive towards oxidative cleavage
b. The oxygens are added across a double bond, basically splitting
the double bond in half

13. Predicting addition products

a. Analyze the reagents used to determine what groups will be
added across the C=C double bond
b. Determine the Regioselectivity (Markovnikov or antiMarkovnikov)
c. Determine the Stereospecificity (syn or anti addition)

Chapter 11: Radical Reactions (Lecture 23)

All Chapter 11 problems will be from Wileyplus (2-3 at mos)t

1. Introduction to radicals
a. Free radicals form when a bond breaks homolytically

45

i. One electron goes onto each of the two atoms

2. Fishhook arrows
a. Used to indicate the movement of a single electron

3. Radical stability
a. Free radicals can be thought of as sp2
b. Free radicals have no charge, but are unstable.
i. In many ways, they behave like a carbocation
c. Are stabilized by substitution via hyperconjugation

d. Free radical resonance

i. Similar to two-electron resonance structures, but use
fishhook arrows instead.
ii. Resonance stabilizes a radical
iii. Compare allyl anion to allyl radical

46

iv. Vinylic radicals are especially unstable

v. Free radicals do not rearrange

4. Six main radical mechanisms
a. Homolytic cleavage

47

b. Addition to a pi bond

c. Hydrogen abstraction

d. Halogen abstraction

e. Elimination

48

f. Coupling

g. Note the reversibility of the processes

5. Steps in a radical chain reaction

a. Initiation
i. Radicals are created
1. Homolytic cleavage
b. Propagation
i. Radicals are moved from one location to another
1. Addition to a pi bond
2. Hydrogen abstraction
3. Halogen abstraction
4. Elimination
c. Termination
i. Radicals are destroyed
1. Coupling
6. Radical Halogenation
a. Chlorination
i. Both steps are exothermic
b. Bromination
49

i. First step is endothermic

ii. Second step is exothermic
7. Allylic bromination
a. When a C=C bond is present it affects the Regioselectivity of the
reaction
b. When an allylic hydrogen is abstracted it leaves behind an allylic
free radical that is resonance stabilized.
c. Use NBS as a source of bromine radicals
i. Only generates Br radical, does not do addition reactions

8. Anti-Markovnikov hydrohalogenation
a. If a peroxide is present, anti markovnikov addition will occur
i. Due to a radical mechanism, since the O-O bond can break
homolytically

b. The mechanism

50

51