Organic Chemistry
Courtney Eichengreen
courtney.eichengreen@ucdenver.edu
719.321.4187
1
Organic Chemistry I

From atoms to molecules and beyond
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Functional Groups
Bonding and Molecular Structure
Resonance and Isomers
Intermolecular interactions
Hydrocarbons
Substitution and Elimination Reactions
Oxygen Containing Compounds
Amines
2
Lewis Dot Structures

Rules for writing


Find total # valence e1 e- pair = 1 bond; Arrange remaining e- per octet rules


Except: Period 3 can have expanded octet (vacant d orbital
required for hybridization)
Formal Charge



# valence e- (isolated atom) - # valence e- (lewis structure)
Sum of formal charge for each atom is the total charge on
the molecule
ACTUAL charge distribution depends on electronegativity
3
Structural Formulas

Dash Formula
Condensed Formula
Bond-line Formula
Fischer projection
Newman projection
Dash-line-wedge
Ball and stick

All Images courtesy of Exam Krackers
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4
Functional Groups
List #1- Critical for the MCAT
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Alkane
Alkene
Alkyne
Alcohol
Ether
Amine
Aldehyde
Ketone
Carboxylic Acid
Ester
Amide
C-C
C=C
CΞC
R-OH
R-O-R
R-N-R2
R-CHO
R2C=O
RCOOH
RCOOR
RCONH2
5
Functional Groups
List #2- Also Useful
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Alkyl
Halogen
Gem-dihalide
Vic dihalide
Hydroxyl
Alkoxy
Hemiacetal
Hemiketal
Mesyl group
Tosyl group
Carbonyl
Acetal
Acyl
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Anhydride
Aryl
Benzyl
Phenyl
Hydrazine
Hydrazone
Vinyl
Vinylic
Allyl
Nitrile
Epoxide
Enamine
Imine
Nitro
Nitroso
6
7
Bonds

Types:

Ionic
complete transfer of electrons

Covalent
shared electrons

Coordinate covalent
One atom provides both electrons in a
shared pair.

Polar covalent
unequal sharing of electrons

Hydrogen Bonds
bonds between polar molecules
containing H and O, N, or F
8
Covalent Bonds

Sigma s



Between s orbitals
Small, strong, lots of rotation
Pi P


Between p orbitals
Discreet structure, weaker than sigma, no rotation
9
Covalent Bonds
10
Bonds

A.
B.
C.
D.
In the pi bond of an alkene, the electron pair have:
33% p character and are at a lower energy level
than the electron pair in the s bond.
33% p character and are at a higher energy level
than the electron pair in the s bond.
100% p character and are at a lower energy level
than the electron pair in the s bond.
100% p character and are at a higher energy level
than the electron pair in the s bond.
11
Hybridization
12
Hybridization

Remember:

All pi bonds are between P orbitals
“Leftover” P and S orbitals hybridize,
participate in sigma bonds

Ex: H2C=CH2

13
Hybrid Bonds
Suffix
C bonds
Hybridiz
ation
Percent
S:P
Bond
Angle
Bond
Length
Bond
Strength
-ane
-ene
-yne
-yl
14
Hybrid Bonds
Suffix
C bonds
Hybridiz
ation
Percent
Bond
Angleo
Bond
Length
(pm)
Bond
Strength
(kJ/mol)
S:P
-ane
C-C
sp3
25:75
109.5
154
346
-ene
C=C
sp2
33:66
120
134
612
-yne
C=C
sp
50:50
180
120
835
-yl
Side
chain
15
Special Cases – O and N

Know typical bonding for C, N, O

Bond angles in N compounds
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Lone pair occupies more space than sigma bond
Bond angles 107.3
Bond angles in O compounds

Bond angles 104.5
16
For the molecule 1,4 pentadiene, what
type of hybridization is present in
carbons # 1 and # 3 respectively?
A) sp2, sp2
B) sp2, sp3
C) sp3, sp3
D) sp3, sp2
17
VSEPR: molecular geometry
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
valance shell electron pair repulsion
GEOMETRY = Minimize electron repulsion
18
VSEPR
1. Draw the Lewis dot structure
2. Place electron pairs as far apart as possible
then large atoms, then small atoms
3. Name the molecular structure based on the position of the atoms
molecule
Lewis structure
Shape
molecule
Lewis structure
Shape
BeCl2
Linear, sp
SF4
Seesaw
SO3
Trigonal
planar, sp2
ICl3
T shaped
NO2-
Bent
CH4
Tetrahedral, sp3
NH3
Trigonal
Pyramidal
PCl5
Trigonal
bipyramidal,
dsp3
SF6
Octahedral
, d2sp3
IF5
Square Pyramidal
ICl4-
Square
Planar
19
We’ve seen static properties of atoms and molecules…
NOW LET’S MOVE STUFF AROUND!
20
Delocalized e- and Resonance

Resonance forms differ only in location of e


To be a significant resonance form, must be stable
Remember octet rule, and consider formal charge
Real structure = blend of possible resonance
structures, “resonance hybrid”
21
Resonance: Acids and Bases

Conjugate stabilized by RESONANCE

Organic Acids- Presence of positively charged H+



present on a OH such as methyl alcohol
present on a C next to a C=O such as acetone (alpha C)
Organic Bases- Presence of lone pair e to bond to H


Nitrogen containing molecules are most common
Oxygen containing molecules can act as bases w strong acids
22
Stereochemistry

Isomers: same molecular formula, different
spatial arrangements

Different spatial arrangements 
different physical and chemical properties!
23
Stereochemistry: Isomers
CONNECTIVITY
Structural
(constitutional) isomers:
Different connectivity.

C4H10 - Isobutane vs n-butane
Same
connectivity, different spatial arrangement:
Stereoisomers
24
Stereochemistry: Isomers
ROTATION
Conformational
isomers: Different spatial
arrangement of same molecule, but doesn’t require
bond breaking to interconvert!

“rotational” isomers

Chair vs. boat, Staggered vs Eclipsed, Gauche vs Anti
DOES
require bond breaking to interconvert:
configurational isomers
25
Stereochemistry: Isomers
DOUBLE BOND

Geometric isomers: differ in arrangement about a
double bond
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Cis vs. trans
Stereoisomers that are not rotational and have no
double bond: OPTICAL isomers
26
Stereochemistry: Isomers
CHIRAL ARRANGEMENT
Enantiomers:


non-superimposable mirror images
Same physical properties (MP, BP, density, solubility,
etc.) except rotation of light and reactions with other
chiral compounds
Chiral centers that are all opposite each other (R/S)
Diastereomers:
chiral molecules with other than
exactly opposite stereocenters (not mirror images)
27
Stereochemistry: Isomers
What kind of isomers are the two compounds below?
A. Diastereomers
B. Enantiomers
C. Constitutional isomers
D. Geometric Isomers
28
Stereochemistry: Rotating Light
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Enantiomers differ in rotation of plane-polarized light
 Excess of one enantiomer causes rotation:
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Right, clockwise, dextrarotary (d), or +
Left, counterclockwise, levarotary (l), or –
Specific rotation [a] = a / (l*d)

Racemic: 50:50 mixt of enantiomers, NO net rotation

Same as R and S? NO

Meso molecule – NO net rotation, internal symmetry
29
Stereochemistry: Chirality
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R and S:
1. Assign priority by atomic number

If attachments are the same, look at the b atoms
2. Orient lowest priority (#4) away from the observer
3. Draw a circular arrow from 1 to 2 to 3
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R = clockwise
S = counterclockwise
E and Z: Different than cis and trans
 Z= same side of high priority groups
 E=opposite side of high priority groups
30
Now we know everything about what happens WITHIN molecules…
WHAT ABOUT BETWEEN MOLECULES?
31
Intermolecular interactions
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Due to DIPOLE MOMENTS
Charge distribution of bond is unequal
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Induced Dipoles
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Molecule with dipole moment = polar
Molecule without dipole moment = nonpolar
Possible to have nonpolar molecules with polar bonds
Spontaneous dipole moment in nonpolar molecule
Occurs via: polar molecule, ion, or electric field
Instantaneous Dipole

Due to random e- movement
32
Intermolecular interactions
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London Dispersion Forces
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Dipole-dipole interactions
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Between 2 instantaneous dipoles
Dipole-dipole or dipole-induced dipole
Hydrogen Bonds

Strongest dipole-dipole interaction
33
When albuterol is dissolved in water, which of the
following hydrogen-bonded structures does NOT
contribute to its water solubility?
34
The first and simplest class of molecules we
need to get friendly with for Test Day:
HYDROCARBONS
35
IUPAC Naming Conventions
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IUPAC Rules for Alkane Nomenclature
1. Find + name the longest continuous carbon chain.
2. Identify and name groups attached to this chain.
3. Number the chain consecutively, starting at the end
nearest highest priority (oxidation) substituent group.
4. Name the compound listing groups in alphabetical
order, preceded by their number in the compound.
(di, tri, tetra etc., don’t count for alphabetizing).

MCAT secret: on Test Day, you’ll only ever have to
MATCH to the correct name!
36
Hydrocarbons
# of C
Root Name
# of C
Root Name
1
meth
6
hex
2
eth
7
hept
3
prop
8
oct
4
but
9
non
5
pent
10
dec
37
Hydrocarbons
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Saturated: CnH(2n+2)
Unsaturated: one or more pi bonds; each pi bond
decreases # of H by 2
Primary, secondary, tertiary, and quaternary carbons
Know and be able to recognize the following structures
n-butyl
sec-butyl
n-propyl
iso-butyl
tert-butyl
Iso-propyl
38
Alkanes
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Physical Properties:
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Straight chains: MP and BP increase with length
Branched chains:
 BP decreases (less surface area,  vDW forces)
 MP – a little more complicated due to crystal structure
 When compared to the straight chain analog, the straight
chain will have a higher MP than the branched molecule.
BUT, amongst branched molecules, the greater the
branching, the higher the MP.
39
Alkanes-Important Reactions
Pretty Darn Unreactive
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Combustion:
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Alkane + Oxygen + High energy input (fire)
Products: H2O, CO2, Heat
Halogenation
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Initiation with UV light
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Propagation (chain reaction mechanisms)
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Homolytic cleavage of diatomic halogen
Yields a free radical
Halogen radical removes H from alkyl
Yields an alkyl radical, which can make more radicals
Termination

Radical bonds to another radical
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Reactivity of halogens: F > Cl > Br >>> I
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Selectivity of halogens (How selective is the halogen in choosing a position on an alkane):

I > Br > Cl > F
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more electronegative means less selective
Stability of free radicals: more substituted = more stable, so halogenation @ most sub’d C

aryl>>>alkene> 3o > 2o > 1o >methyl
40
Cycloalkanes
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General formula: (CH2)n or CnH2n
Nomenclature: It’s the same!
As MW increases BP increases; MP fluctuates
(crystal stacking with different geometry)
Ring strain in cyclic compounds:


Zero for cyclohexane (All C-C-C bond angles: 111.5°)
Increases as rings become smaller or larger (up to cyclononane)
41
http://www.chem.uh.edu/Courses/Thummel/Chem3331/Notes/Chap3/
Cycloalkanes
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Cyclohexane


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Exist as “chair” and “boat” conformations
Chair conformation preferred because it is at the lowest
energy. (WHY?)
Substituents can occupy axial and equatorial positions.
Axia (6) - perpendicular to the ring
Equatorial (6)- roughly in the plane of the ring

Big substituents prefer to be equatorial – less “crowding”!
When
the ring reverses its conformation, substituents
reverse their relative position
42
Cyclohexanes

In a sample of cis-1,2-dimethylcyclohexane
at room temperature, the methyl groups will:
A.
B.
C.
D.
Both be equatorial whenever the molecule is in the
chair conformation.
Both be axial whenever the molecule is in the chair
conformation.
Alternate between both equatorial and both axial
whenever the molecule is in the chair conformation
Both alternate between equatorial and axial but will
never exist both axial or both equatorial at the same
time
43
Things start getting more exciting once we start substituting H for
more interesting functional groups… so let’s get ready for some
REACTIONS!!
44
Substitutions
Substitution:
one functional group replaces another


Electrophile: wants electrons,
has partial + charge

Nucleophile: donates electrons,
has partial – charge
45
Eliminations
Elimination:
functional group lost, double bond made



Often, a Lewis base is responsible for taking H
leaving behind an extra pair of e- for the =
The opposite of elimination is addition
46
Substitution and Elimination

SN1: substitution, nucleophilic, unimolecular

Mechanism: two-step

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1. spontaneous formation of carbocation (SLOW)
2. Nucleophile attacks carbocation
Kinetics: rate depends only on the substrate, R=k[reactant]
Stereochemistry: racemization of chiral substrates
Favored with weak or bulky Nu, good LG, stable carbocation


Protic solvents stabilize carbocation
Can see carbocation rearrangement
47
Substitution and Elimination

E1: elimination, unimolecular

Mechanism: two-step

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
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1. spontaneous formation of carbocation (SLOW)
2. Base abstracts beta H
Kinetics: rate depends only on the substrate, R=k[reactant]
Favored with good LG, stable carbocation, weak base


Protic solvents stabilize carbocation
Can see carbocation rearrangement
48
Which of the following
carbocations is the most stable?
A
. CH3CH2CH2CH2
B
. CH3CH2CH2CHCH3
C
. (CH3)3C
D
. CH3
49
Substitution and Elimination

SN2: substitution, nucleophilic, bimolecular



Mechanism: CONCERTED
Kinetics: rate depends on substrate+nucleophile, R=k[Nu][E]
Stereochemistry: inversion of configuration


(but watch your R and S!)
Favored with poor LG, small + strong Nu

Polar, APROTIC solvents don’t obstruct Nu
50
Substitution and Elimination

E2: elimination, bimolecular

Mechanism: CONCERTED


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Anti-peri-planar transition state determines stereochemistry
Kinetics: rate depends on substrate+base, R=k[substrate][B]
Favored with strong bulky base


If you see HEAT, think Elimination
E2 reactions often run in solvent of conjugate acid (WHY?)
51
Benzene

A special molecule, a special case of substitution!

Actually, it’s addition and then elimination.

Aromatic molecule, Stabilized by resonance
Undergoes net substitution not addition (WHY?)

Substituents determine subsequent reactivity:

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Electron donating groups activate the ring and are ortho-para directors
Electron withdrawing groups deactivate the ring and are meta directors
Halogens are electron withdrawing BUT are ortho-para directors
52
Benzene: Substituent Effects
53

In what order were the substituents added?
How can you tell?
54
Another class of molecules we need to be familiar with:
OXYGEN-CONTAINING COMPOUNDS
55
Oxygen Containing Compounds
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
Alcohols
Aldehydes and Ketones
Carboxylic Acids
Acid Derivatives
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Acid Chlorides
Anhydrides
Amides
Keto Acids and Esters
56
Alcohols
One of the most common reactions of alcohols is
nucleophilic substitution. Which of the following
are TRUE in regards to SN2 reactions:
Inversion of configuration occurs
Racemic mixture of products results
Reaction rate = k [S][nucleophile]
I.
II.
III.
A.
B.
C.
D.
I only
II only
I and III only
I, II, and III
57
Alcohols

Physical Properties:



Polar
High MP and BP (WHY?)
More substituted = less acidic





(CH3)3COH:
CH3CH2OH:
CH3OH:
pKa = 18.00
pKa = 16.00
pKa = 15.54
Electron withdrawing substituents stabilize alkoxide ion and lower pKa.
 Tert-butyl alcohol:
pKa = 18.00
 Nonafluoro-tert-butyl alcohol: pKa = 5.4
General principles


H bonding
Acidity: weak relative to other O containing compounds
58
Alcohols
Naming



Select longest C chain containing the hydroxyl
group and derive the parent name by
replacing –e ending of the corresponding
alkane with –ol.
Number the chain beginning at the end
nearest the –OH group.
Number the substituents according to their
position on the chain, and write the name
listing the substituents in alphabetical order.
59
Alcohols-Oxidation & Reduction
Oxidation
60
Reduction
Alcohols-Oxidation & Reduction

Common oxidizing and reducing agents

Generally for the MCAT


Oxidizing agents have lots of oxygens
Reducing agents have lots of hydrogens
Oxidizing Agents
K2Cr2O7
KMnO4
H2CrO4
O2
Br2
Reducing Agents
LiAlH4
NaBH4
H2 + Pressure
61
Making Alcohols: reduction
synthesis

Aldehydes, ketones, esters, and acetates can be
reduced to alcohols w strong reducing agents such
as NaBH4 and LiAlH4



Electron donating groups increase the negative charge
on the carbon and make it less susceptible to
nucleophilic attack.
Reactivity: Aldehydes>Ketones>Esters/acetates
Only LiAlH4 is strong enough to reduce esters and acetates
62
Alcohols to Alkylhalides
via a strong acid catalyst

R-OH + HCl  RCl + H20

-OH is converted to a much better leaving group
when protonated by a strong acid


For tertiary alcohols: HCl or HBr
Primary/secondary alcohols are harder, need SOCl2 or
PBr3
63
In the reaction above, if the reagents in the
first step were replaced with LiAlH4, what
product would result?
O
OH
a)
c)

OH
b)
OH
OH
d)
OH
HO
OH
64
Carbonyls
Carbon double bonded to Oxygen





Planar stereochemistry
Partial positive charge on Carbon
(susceptibility to nucleophilic attack)
Aldehydes & Ketones (nucleophilic addition)
Carboxylic Acids (nucleophilic substitution)
Amides
65
Aldehydes and Ketones

Physical properties:





Carbonyl group is polar
Higher BP and MP than alkanes (WHY?)
More water soluble than alkanes (WHY?)
Trigonal planar geometry, reduction yields racemic mixtures
General principles:




Effects of substituents on reactivity of C=O: e- withdrawing increase
the carbocation nature and make the C=O more reactive
Steric hindrance: ketones are less reactive than aldehydes
Acidity of alpha hydrogen: carbanions
a, b unsaturated carbonyls: resonance structures
66
Aldehydes and Ketones
Naming – lalala it’s the same rules!

Naming Aldehydes





Replace terminal –e of corresponding alkane with –al.
Parent chain must contain the –CHO group
The –CHO carbon is C1
When –CHO is attached to a ring, we say “carbaldehyde”
Naming Ketones



Replace terminal –e of corresponding alkane with –one.
Parent chain is longest chain containing ketone
Numbering begins at the end nearest the carbonyl C.
67
Aldehydes and KetonesAcetal and Ketal Formation
nucleophilic addition at C=O bond
68
Aldehydes and Ketones

Keto-enol Tautomerism:

Keto tautomer is preferred (alcohols are more
acidic than aldehydes and ketones).
69
Guanine, the base portion of guanosine, exists as
an equilibrium mixture of the keto and enol forms.
Which of the following structures represents the
enol form of guanine?
70
Aldehydes and Ketonesreactions at adjacent positions

Aldol (aldehyde + alcohol) condensation:

Occurs at the alpha carbon



Pi electrons in enol act as nucleophile
Base catalyzed condensation (removal of H2O)
Can use mixtures of different aldehydes and ketones
71
Aldehydes and Ketones-Oxidation
(Aldehydes  Carboxylic acids)

Aldehydes are easy to oxidize because of the
adjacent hydrogen. In other words, they are good
reducing agents.

Examples used as indicators:




Potassium dichromate (VI): orange to green
Tollens’ reagent (silver mirror test): grey ppt.
Fehlings or benedicts solution (copper solution): blue to red
Ketones (no adjacent H)
are resistant
to oxidation.
72
Aldehydes and Ketones

Organometallic reagents:

Nucleophilic addition of a carbanion to an
aldehyde or ketone to yield an alcohol
73
Carboxylic Acids
General


Electrophilic carbonyl C susceptible to nucleophilic
attack!
Fairly strong acids (compared to other organic
Oxygen containing compounds)


Principles:
Acidity of terminal H increases with EWG, decreases
with EDG – always consider stability of conjugate base
Planar, polar, H bonding
74

Which class of compounds would have a
higher boiling point, Acyl Chlorides or
Carboxylic Acids? Why?
75
Carboxylic Acids
Naming
Carboxylic acids derived from open chain
alkanes are systematically named by
replacing the terminal –e of the
corresponding alkane name with –oic acid.
Compounds that have a –CO2H group
bonded to a ring are named using the suffix
–carboxylic acid.



The –CO2H group is attached to C #1 and is not
itself numbered in the system.
76
Carboxylic Acids-important
reactions

Carboxyl group reactions:

Nucleophilic attack:

Carboxyl groups and their derivatives undergo
nucleophilic substitution.


Aldehydes and Ketones undergo addition (WHY?)
Must contain a good leaving group or a substituent
that can be converted to a good leaving group.
77
Carboxylic Acids-important
reactions

Reduction:


Form a primary alcohol
LiAlH4 is the reducing agent
CH3(CH2)6COOH
LiAlH4
CH3(CH2)6CH2OH
78
Carboxylic Acids-important
reactions

Carboxyl group reactions:

Decarboxylation: know that it happens (-CO2)
79
Carboxylic Acids-important
reactions

Fischer Esterification Reaction:

Alcohol + Carboxylic Acid  Ester + Water


Acid Catalyzed- protonates –OH to H2O (excellent
leaving group)
Alcohol performs nucleophilic attack on carbonyl
carbon
H+
These bonds are
broken
80
Carboxylic Acidsreactions at two positions

Substitution reactions: keto reactions shown,
consider enol reactions
To make >
SOCl2
or PCl3
Heat, -H2O
R'OH, heat,
H+
-
R2NH
heat
HO81
Carboxylic Acidsreactions at two positions

Halogenation: enol tautomer undergoes
halogenation
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Acid Derivatives
Naming

Acid Halides (RCOX)


Acid Anhydrides (RCO2COR’)



Just replace the word acid with anhydride.
 2 acetic acid  acetic anhydride
Unsymmetrical anhydrides are named by citing the two acids
alphabetically.
 Acetic acid + benzoic acid  acetic benzoic anhydride
Esters (RCO2R’)


“-oyl halide” instead of “-oic acid” ex: ethanoyl chloride
Name R’ (on the –O– side) with “-yl”, R (on the =O side) with “-oate”
ex: isopropyl propanoate
Amides (RCONH2)


Just use the suffix “amide”
 Acetic acid  acetamide
If the Nis further substituted, first identify the substituent groups and
then the parent amide. The substituents are preceded by the letter N.
83
 Propanoic acid + methyl amine  N-Methylpropanamide
Acid DerivativesRelative Reactivity



A more reactive acid
derivative can be converted
to a less reactive one, but not
vice versa
Only esters and amides
commonly found in nature.
Acid halides and anhydrides
react rapidly with water and
do not exist in living
organisms
84
85
Acid Derivatives- Reactions of
Derivatives
•Hydrolysis- +water  carboxylic acid
•Alcoholysis- +alcohol  ester
•Aminolysis- +ammonia or amine  amide
•Reduction- + H-  aldehyde or alcohol
•Grignard- + Organometallic  ketone or alcohol
86
Acid Derivatives
Transesterification


Transesterification: exchange alkoxyl group
with ester of another alcohol
Alcohol + Ester  Different Alcohol +
Different Ester
87