Chemistry 3719 – Introduction to Organic Chemistry 1
Professor:
Dr. Peter Norris
Office:
6014 Ward Beecher
MTW 4-5 pm
Phone:
(330) 941-1553
Email:
pnorris@ysu.edu
http://dr‐peter‐norris.com
YSU
Chemistry 3719 – Introduction to Organic Chemistry 1
1965
Born Liverpool, Lancashire, England
1986
B.Sc. Chemistry, Salford University, England
1992
Ph.D. Organic Chemistry, Ohio State University
1993-96
Post-doctoral, American University, Wash’n DC
1996-00
Assistant Professor, YSU Chemistry
2000-04
Associate Professor. YSU Chemistry
2004-
Full Professor, YSU Chemistry
____________________________________________________
~50 publications, graduated 37 Masters degree students since 1998
~ $1,000,000 in grant money since 1999
YSU
1
Chemistry 3719 – Introduction to Organic Chemistry 1
Lecture needs:

Carey (7 or 8)

Molecular models

Adobe Acrobat Reader

Web access
Molecular Models
www.darlingmodels.com
YSU
Chemistry 3719 – Introduction to Organic Chemistry 1
Lab needs:

Pavia, Lampman, Kriz & Engel

Goggles

Lab coat

Bound notebook
YSU
2
Chemistry 3719 – Introduction to Organic Chemistry 1
Lab needs:

Pavia, Lampman, Kriz & Engel

Goggles

Lab coat

Bound notebook
Strongly Recommended:

Downloading and installing the ChemDraw software

Free access to anyone with a YSU email address

Useful for drawing chemical structures and spectra

Instructions for download linked to 3719 webpage
YSU
Chemistry 3719 – Introduction to Organic Chemistry 1
Lectures

Structure and nomenclature of compounds and groups

Physical properties and analysis of materials 
Reactivity and transformations with reagents

Importance of organic compounds in other subjects
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3
Chemistry 3719 – Introduction to Organic Chemistry 1
Lectures

Structure and nomenclature of compounds and groups

Physical properties and analysis of materials 
Reactivity and transformations with reagents

Importance of organic compounds in other subjects
Labs

Glassware and equipment used to prepare organics 
Instrumentation used to analyze compounds

Keeping a good notebook of lab preparations
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Chemistry 3719R – Recitation
Objectives

Practice the available problem sets, old exams

Practice the problems from the textbook

Ask questions in a smaller group setting

Encourages students to keep up with material (quizzes)
When: 11-12.10 on Monday, Wednesday
(1 Semester hour, Separate grade to 3719/3719L)
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Student Comments on Chemistry 3719
“Norris is extremely approachable. Study this stuff, ask questions you should
get at least a B in this course.”
YSU
Student Comments on Chemistry 3719
“Norris is extremely approachable. Study this stuff, ask questions you should
get at least a B in this course.”
“O Chem is not supposed to be easy but Norris gives you plenty of practice
problems and multiple ways to get ahold of him if you have questions. Seems
intimidating but is very approachable.”
YSU
5
Student Comments on Chemistry 3719
“Norris is extremely approachable. Study this stuff, ask questions you should
get at least a B in this course.”
“O Chem is not supposed to be easy but Norris gives you plenty of practice
problems and multiple ways to get ahold of him if you have questions. Seems
intimidating but is very approachable.”
“Better off taking Dr. Jackson using Dr. Norris' notes and released exam(s).
Norris is NOT that good as people have said. I ended up teaching myself
everything.“
YSU
Student Comments on Chemistry 3719
“Norris is extremely approachable. Study this stuff, ask questions you should
get at least a B in this course.”
“O Chem is not supposed to be easy but Norris gives you plenty of practice
problems and multiple ways to get ahold of him if you have questions. Seems
intimidating but is very approachable.”
“Better off taking Dr. Jackson using Dr. Norris' notes and released exam(s).
Norris is NOT that good as people have said. I ended up teaching myself
everything.“
“Norris is very open to answer questions during class and opens himself up to
help at all hours of the day and night. If you keep up with the material then you
can do really well.”
YSU
6
Student Comments on Chemistry 3719
“Norris is extremely approachable. Study this stuff, ask questions you should
get at least a B in this course.”
“O Chem is not supposed to be easy but Norris gives you plenty of practice
problems and multiple ways to get ahold of him if you have questions. Seems
intimidating but is very approachable.”
“Better off taking Dr. Jackson using Dr. Norris' notes and released exam(s).
Norris is NOT that good as people have said. I ended up teaching myself
everything.“
“Norris is very open to answer questions during class and opens himself up to
help at all hours of the day and night. If you keep up with the material then you
can do really well.”
“Norris can be a complete #*&%, however he does know what he’s doing”
YSU
Student Comments on Chemistry 3719
“Norris is extremely approachable. Study this stuff, ask questions you should
get at least a B in this course.”
“O Chem is not supposed to be easy but Norris gives you plenty of practice
problems and multiple ways to get ahold of him if you have questions. Seems
intimidating but is very approachable.”
“Better off taking Dr. Jackson using Dr. Norris' notes and released exam(s).
Norris is NOT that good as people have said. I ended up teaching myself
everything.“
“Norris is very open to answer questions during class and opens himself up to
help at all hours of the day and night. If you keep up with the material then you
can do really well.”
“Norris can be a complete #*&%, however he does know what he’s doing”
Work hard and you’ll do well in 3719 and 3720
YSU
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How to Approach Chemistry 3719

Read ahead before class, slides are posted online

Come to class, pay attention, take good notes

Try to understand (not memorize) material and concepts

Ask questions in class, don’t be shy about doing so

Sign up for the recitation class (3719R) and attend

Sign up available tutoring sessions (CSP, grad students)

Do problems daily (book, online exams and worksheets)

Use office hours as often as possible, starting now
Use the tools at your disposal and you will do well;
Leave it until the week of a test and you will probably fail
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What Else To Be Concerned About

Do not, under any circumstance, use a cellphone in class

Texting, emailing, surfing, etc. will get you an F

If you plan on finding a real job or going to graduate/
professional school after YSU then you need to start building
a CV which includes solid references

Professors will refuse to write you letters if they don’t know
who you are, use office hours, introduce yourself

Ask for advice as soon as possible, especially if you are
applying to graduate or professional school

Start being proactive in getting yourself where you want to be
and you’ll improve your chances of getting there
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Chemistry 3719 Online Resources

Webpage – www.dr-peter-norris.com

Syllabus, lab information

Problem sets – practice with important concepts and
reactions

Old exams and (very detailed) answer keys – use them as
guides, do not memorize them
http://dr-peter-norris.com
YSU
Michigan State Online Textbook
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What is Organic Chemistry?
The study of the compounds that contain carbon and the reactions
of those materials (millions known, many millions more possible)
Why a whole year of Organic?
Carbon can bond in multiple ways to form a huge number of different
molecules, and these compounds form the basis of many different
disciplines, e.g.:
Biology (DNA, proteins, carbohydrates, lipids, steroids, etc.)
Medicine and Pharmacy (Aspirin, Taxol, AZT, Lipitor, etc.)
Chemical Engineering (oil, plastics, fine chemicals, materials)
Forensics (biological materials, chemical tests, analytical tools)
YSU
Organic Chemistry – Materials and Uses
chemical
synthesis
New
Materials
materials
chemistry
New
Compounds
Biochemistry
and
Chemical Biology
Nanotech,
Engineering
Proteomics,
Genetics
Pharmacy,
Medicine
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Organic Chemistry – Biology, Pharmacy, Medicine, etc.
OH OH
O
CO2H
OH
AcHN
OH
N-acetylneuraminic acid
O
CO2Et
AcHN
NH3.HPO4
Tamiflu - Giliad/Roche
OH OH
O
CO2H
OH
AcHN
H2N
NH
Relenza - GSK
From Scientific American – www.sciam.com
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Teaching Philosophy – Organic Chemistry is a Language
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Teaching Philosophy – Organic Chemistry is a Language
H
O
O
CH3 C CH2CH3
H+, H2O
CH3 C C CH3
H
H
H
H
O
H
H
O
CH3 C C CH3
H
O
H
H
CH3 C C CH3
O
CH3 C CH2CH3
H
H
H
O
H
H
H
O
CH3 C C CH3
O
CH3 C CH2CH3
H
H
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Chemistry 3719 and 3720
H
C
H
H
H
~1800 : Organic Chemistry : the chemistry of natural
products based on carbon
2013 : Organic Chemistry : “molecular engineering”
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Organic Chemistry Timeline
1807
Berzelius introduces the term “Organic Chemistry” to describe the study of compounds isolated from nature
1828
Wöhler makes urea, the first natural organic compound to be synthesized in the laboratory
1890
Emil Fischer studies the chemistry of proteins, carbohydrates and the nucleic acids ‐ Biochemistry
1950
Woodward and Eschenmoser complete the first total synthesis of Vitamin B12. NMR begins to be useful.
1990
Kishi, Nicolau, Smith, Schreiber, etc. complete total syntheses of compounds such as Brevetoxin B, Taxol, Palytoxin, etc. 2013
Chemical Biology, Molecular Engineering
YSU
Organic Chemistry – Progress
Movassaghi, Tjandra, Qi. JACS, 2009, ASAP
www.totallysynthetic.com/blog YSU
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Organic Chemistry 3719 – Overview

Review of basics from the Periodic Table – trends, organization

Molecular geometry based on VSEPR and hybridization

Acids and bases – definitions, factors in acid/base strength

Chemical kinetics and equilibria – recognizing stability factors

Families of organic molecules – alkanes, alkenes, alkynes, etc.

Naming and structures – organizing compounds within groups

Reactivity of each family when challenged with reagents

Description of how bonds form and break during conversions

Use of various factors to predict products of chemical reactions

Application of principles to produce new compounds/materials
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Chemistry 3719 – Introduction to Organic Chemistry 1
Chemistry 3719
Introduction to Organic
Chemistry
Chapter 1
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Chapter 1 – Chemical Bonding
“Structure determines properties”

Atomic and electronic structure of atoms

Ionic and covalent bonding

Electronegativity and polar covalent bonds

Structures of organic compounds - representations

Resonance within molecules

Shapes of molecules

Molecular orbitals and orbital hybridization
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Chapter 1 – Chemical Bonding
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Chapter 1 – Energy Relationships
G = H - TS

Overall energy within a system relies upon enthalpy (H,
e.g. bond strengths) and entropy (S, e.g. the number of
different species present) factors

Energy relates to “stability” and “reactivity” which will
help determine which reactions or molecular shapes are
viable in Chemistry and Biology

Systems (reactions, individual molecules) will try to
become more stable through changes in constitution
(chemical change) or shape (physical change)

Understanding the concepts of stability/reactivity will be
important in both Organic Chemistry and Biochemistry
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1.1 – Atoms, Electrons, & Orbitals
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1.1 – Atoms, Electrons, & Orbitals
Probability distribution for an s electron
Figure 1.1
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1.1 – Atoms, Electrons, & Orbitals
Boundary surfaces of a 1s and 2s orbital
Figure 1.2
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1.1 – Atoms, Electrons, & Orbitals
Boundary surfaces of the 2p orbitals
Figure 1.3
P orbitals in the same level are
degenerate;
equivalent in size, shape, energy, only
differ by direction projected in space
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1.1 – Atoms, Electrons, & Orbitals
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1.1 – Electronic Structure of Atoms
Atom
Atomic No.
Electronic Structure
H
1
1s1
He
2
1s2
Li
3
1s2 2s1
Be
4
1s2 2s2
B
5
1s2 2s2 2px1
C
6
1s2 2s2 2px1 2py1
N
7
1s2 2s2 2px1 2py1 2pz1
O
8
1s2 2s2 2px2 2py1 2pz1
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1.1 – General Concepts in Electronic Structure

Orbitals higher in energy further they are from nucleus.

Designated by principal quantum number (1, 2, 3, etc.).

Degenerate orbitals (same energy) fill up singly before
they double up (Aufbau).

Maximum of two electrons per orbital, each having
opposite spin (Pauli exclusion principle).

Impossible to know both the speed and location of an
electron at the same time (Heisenberg uncertainty).
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1.2-1.3 – General Concepts in Chemical Bonding
Atoms trying to attain the stable configuration of
a noble (inert) gas - often referred to as the
octet rule
1.2 Ionic Bonding ‐ Electrons Transferred
1.3 Covalent Bonding ‐ Electrons Shared
type of bond that is formed is dictated by the
relative electronegativities of the elements involved
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Electronegativity
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Important Electronegativity Values
H
2.1
Li
1.0
Be
B
2.0
C
2.5
N
3.0
O
3.5
F
4.0
Cl
3.0
Br
2.8
I
2.5
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1.3 – Lewis Dot Structures of Molecules
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1.4 – Double Bonds and Triple Bonds
Double bonds ‐ alkenes
H H
C::C
H H
H
H
C C
H
H
Triple bonds ‐ alkynes
H:C:: :C: H
H C
C H
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1.5 – Polar Covalent Bonds and Electronegativity
H2
HF
CH4
H2O
CH3Cl
Based on electronegativity differences
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1.6 – Formal Charge
Formal Charge = group number
‐ number of bonds
‐ number of unshared electrons
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1.7 – Structural Formulae : Shorthand
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1.8 – Resonance Structures : Electron Delocalization
Table 1.6 – formal rules for resonance
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1.9 – Writing Structures : Constitutional Isomers
Same molecular formula, completely different chemical, physical
and biological/pharmacological properties
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1.10 – Shapes of Organic Molecules
Shapes of molecules are predicted
using VSEPR theory
CH4 is tetrahedral
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1.10 – Shapes of Organic Molecules
Figure 1.9
Table 1.7 – VSEPR and molecular geometry
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1.10 – Shapes of Organic Molecules
Table 1.7
VSEPR
&
Molecular
Geometry
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1.10 – Shapes of Organic Molecules
Trigonal planar geometry of bonds to carbon in H2C=O
Linear geometry of carbon dioxide
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1.11 – Molecular Dipole Moments
Figure 1.7
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1.12 – Curved Arrows : Extremely Important

Curved arrows used to track flow of electrons
in chemical reactions

Consider reaction shown below which
shows the dissociation of A-B
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1.12 – Curved Arrows : Describing Reactions
Many reactions involve both bond breaking
and bond formation.
More than one arrow may be required.
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1.13-1.14 – Acids and Bases : Definitions
Arrhenius
An acid ionizes in water to give protons. A base ionizes in
water to give hydroxide ions.
Brønsted-Lowry
An acid is a proton donor. A base is a proton acceptor.
Lewis
An acid is an electron pair acceptor. A base is an electron
pair donor.
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1.13-1.14 – Acids and Bases : Definitions
Curved arrows are used to describe how
bonds are formed and broken
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Proton Transfer From HBr to Water
Hydronium ion
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Equilibrium Constants for Chemical Reactions
Reactants
Products
Equilibrium Constant (K) = [Products]
[Reactants]
G = H – TS
G = ‐ RTlnK
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Equilibrium Constants for Chemical Reactions
Left-Side
Right-Side
Equilibrium Constant (K) = [Right-Side]
[Left-Side]
G = ‐ RTlnK
K > 1, RHS favoured; K ~ 1, equal; K < 1, LHS favoured
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Equilibrium Constant for Proton Transfer
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Acids and Bases : Arrow Pushing
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Acidity Constants From Text
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Acidity Constants to be Memorized
Need to know by next class:
• pKa = -log10Ka
• Strong Acid = LOW pKa
Weak Acid = HIGH pKa
HI, HCl, HNO3, H3PO4
pKa -10 to -5
H3
O+
Super strong acids
pKa – 1.7
RCO2H
pKa ~ 5
acids
PhOH
pKa ~ 10
get
H2O, ROH
pKa ~ 16
weaker
RCCH (alkynes)
pKa ~ 26
RNH2
pKa ~ 36
Extremely weak
RCH3
pKa ~ 60
Not acidic at all
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1.15 – What Happened to pKb?

A separate “basicity constant” Kb is not necessary

Because of the conjugate relationships in the BrønstedLowry approach, we can examine acid-base reactions
by relying exclusively on pKa values
H
H C H
H
H
H C
H
pKa ~60
Corresponding base
Not at all acidic
Extremely strong
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1.16 – How Structure Affects Acid-Base Strength
pKa
HF
HCl
HBr
HI
3.1
-3.9
-5.8
-10.4
weakest acid
strongest acid
strongest H—X bond
weakest H—X bond
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Inductive Effects
Electronegative groups/atoms remote from the acidic H
can affect the pKa of the acid.
pKa = 16
pKa = 11.3

O–H bond in CF3CH2OH is more polarized by EWG

CF3CH2O- anion is stabilized by EW fluorine atoms
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Resonance Stabilization in Anion
Delocalization of charge in anion (resonance) makes the anion
more stable and thus the conjugate acid more acidic
• e.g. (CH3CO2H > CH3CH2OH):
pKa ~16
pKa ~5
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1.17 – Acid-base Reactions : Equilibria
NaCl
H Cl + NaOH
O
H3C
+
H2O
O
OH
+ NaOH
H3C
ONa
+ H2O
CH3ONa + H2O
CH3OH + NaOH
The equilibrium will lie to the side of the
weaker conjugate base
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1.18 – Lewis Acids and Lewis Bases
Product is a stable substance. It is a liquid with a boiling point
of 126 °C. Of the two reactants, BF3 is a gas and
CH3CH2OCH2CH3 has a boiling point of 34 °C.
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Chapter 2 – Hydrocarbon Frameworks : “Alkanes”
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2.2-2.3 – Chemical Bonding
Figure 2.3 – Valence bond picture for H2
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2.2-2.3 – Chemical Bonding : Two Possibilities
Figure 2.5 – bond and antibond possibilities for H2
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2.4 – Molecular Orbitals by Combining Atomic Orbitals
Figure 2.6 – bond and antibond possibilities for H2
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2.5 – Simple Alkanes : Methane, Ethane, Propane
-160 oC
-89 oC
-42 oC
Figure 2.7 – Low molecular weight alkanes
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2.6 – sp3 Hybridization and Bonding in Methane
Figure 2.9 – Hybridization picture for C in CH4
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2.6 – sp3 Hybridization and Bonding in Methane
Figure 2.10 – Hybrid orbital picture for C in CH4
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2.7 – sp3 Hybridization and Bonding in Ethane
Figure 2.11 – sp3-sp3 interaction in ethane
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2.8 – Isomeric Alkanes : the Butanes
C4H10 n‐butane
C4H10 isobutane
Structural Isomers
Same molecular formula, different
bonding arrangement
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2.9-2.10 – Higher Alkanes : the C5H12 Isomers
C5H12
n‐pentane
C5H12
isopentane
C5H12 neopentane
Structural Isomers
Same molecular formula, different
bonding arrangement
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2.10 – Higher Alkanes : Structural Diversity
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Careful With Drawing Chains
CH3CHCH2CH 3
CH3
CH3
CH 3CH2CHCH3
CH3
CH3CHCH2CH 3
CH 3
CH 2CH2CH 3
CH 3
CH 3
CH3CH2CHCH 3
All the same compound!
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2.11-2.12 – Alkane Nomenclature : Need to Know to C-12
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2.11-2.12 – Alkane Nomenclature : Need to Know to C-12
IUPAC Rules:

Find the longest continuous carbon chain

Identify substituent groups attached to the chain

Number the chain so as to keep numbers small

Write the name in the following format:
Numerical location ‐ [substituent(s)][parent alkane]
e.g. 2,3-dimethylheptane
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2.12 – IUPAC Rules : How to Apply Them
Hexane (IUPAC); n-hexane (common)
2-methylhexane not 5-methylhexane
2,4-dimethylheptane
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2.11-2.12 – Alkane Nomenclature : Need to Know to C-12
Replace -ane ending with -yl
primary (1o)
secondary (2o)
tertiary (3o)
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2.13 – Alkyl Groups : Common Names
propyl group
isopropyl group
t‐butyl group
(1‐methylethyl) (1,1‐dimethylethyl)
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2.14 – Highly Branched Alkanes
4‐ethyloctane
4‐ethyl‐3‐methyloctane
4‐ethyl‐3,5‐dimethyloctane
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2.15 – Cycloalkanes
1,1,3-trimethylcyclohexane
2-ethyl-1,1dimethylcyclopentane
(1,1-dimethylethyl)cycloheptane
(notice the “di” is not involved in
the alphabetization)
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2.16 – Sources of Alkanes and Cycloalkanes
Figure 2.12 – Various fractions obtained from crude oil
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2.17 – Physical Properties of Alkanes
Figure 2.15 – Boiling point versus number of carbons
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2.17 – Physical Properties of Branched Alkanes
Figure 2.16 – How branching has an effect on properties
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2.17 – Physical Properties of Branched Alkanes
Alkane properties:

Generally very insoluble in water (“greasy” or “oily”)

Individual molecules interact via van der Waals forces

These intermolecular forces decrease with branching

Alkanes may be combusted in oxygen:
e.g. CH4 + 2O2
CO2 + 2H2O
H = - 213 kcal
i.e. combustion of hydrocarbons releases energy
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2.18 – Heats of Combustion of Alkanes
Figure 2.17 – Heats of combustion of isomeric alkanes
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2.19 – Oxidation-Reducation in Organic Chemistry
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2.20 – sp2 Hybridization in Ethylene
H
H
C C
H
H
Figure 2.18 – Different representations of ethylene
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2.20 – sp2 Hybridization in Ethylene
Figure 2.19 – Hybrid orbitals required for ethylene
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2.20 – sp2 Hybridization in Ethylene
Figure 2.20
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2.21 – sp Hybridization in Acetylene
Figure 2.22
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2.21 – sp Hybridization in Acetylene
Figure 2.23
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2.22 – Bonding in Water and Ammonia
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Chapter 3 – Conformations of Alkanes and Cycloalkanes
G = H - TS
Energy distribution vs. Temp.
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Conformational Analysis – Towards Structural Biology
Thymidine – incorporated into DNA as “T”
Zidovudine (AZT) – incorporated into
DNA instead of T – stops chain growth
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1
3.1 – Conformational Analysis of Ethane
Since single bonds can rotate around the bond axis, different
conformations are possible - conformational analysis
Figure 3.1 – Different representations of ethane - ChemDraw
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3.1 – Conformational Depictions of Acyclic Molecules
Different 3-D depictions of Ethane
“Wedge/dash”
“Sawhorse”
“Newman”
Rotation around the central C-C bond will cause the hydrogens to
interact - rotamers or conformers
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2
3.1 – Definitions for Using Newman Projections
Gauche
torsion angle 60o
Eclipsed
torsion angle 0o
Anti
torsion angle 180o
Both gauche and anti conformers are staggered
Eclipsed conformers are destabilized by torsional strain
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3.1 – Conformational Analysis of Ethane
Figure 3.4 – Rotation around the C‐C bond of Ethane
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3.2 – Conformational Analysis of Butane
Figure 3.5 – Rotation around the C2‐C3 bond of Butane
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3.3 – Conformations of Higher Alkanes
Anti
(staggered)
Gauche
(staggered)
eclipsed
eclipsed
Applicable for any acyclic molecule
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3.4 – Cycloalkanes : Most Not Planar
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3.5 – Cyclopropane and Cyclobutane
Figure 3.10 – Depictions of Cyclopropane and Cyclobutane
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3.6 – Conformations of Cyclopentane
Figure 3.12 – Important Conformations of Cyclopentane
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3.7 – Conformations of Cyclohexane
Conformationally flexible (without breaking bonds)
Chair
Boat
Chair
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3.7-3.8 – Axial and Equatorial Positions in Cyclohexane
Figures 3.13 & 3.14 – Axial and Equatorial positions in cyclohexane chair and boat conformations
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3.9 – Conformational Inversion : Ring-Flipping
Figure 3.18 – Energetics of the ring-flip
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3.10 – Equilibrium Constants for Ring-Flips
Equilibrium Constant (K) = [Products]
[Reactants]
G = H – TS
G = - RTlnK
YSU
3.10 – Equilibrium Constants for Ring-Flips
Equilibrium Constant (K) = [Right-Side]
[Left-Side]
G = - RTlnK
K > 1, RHS favoured; K ~ 1, equal; K < 1, LHS favoured
YSU
8
3.10 – Analysis of Monosubstituted Cyclohexanes
G = -0.24 Kcal/mol
K = 1.5
YSU
3.10 – Analysis of Monosubstituted Cyclohexanes
G = -7.3 Kcal/mol
K = 19
YSU
9
3.10 – Analysis of Monosubstituted Cyclohexanes
G = -8.6 Kcal/mol
K = 32.3
YSU
3.10 – Analysis of Monosubstituted Cyclohexanes
G = -22.8 Kcal/mol
K = >9999
YSU
10
3.10 – Analysis of Monosubstituted Cyclohexanes
Figure 3.19
YSU
3.11 – Disubstituted Cyclopropanes : Stereoisomers
Figure 3.20
YSU
11
3.11 – Disubstituted Cycloalkanes : Stereoisomers
Cis-1,2-dimethylcyclopropane is less stable than the trans isomer
Cis-1,2-dimethylcyclohexane is less stable than the trans isomer
Cis-1,3-dimethylcyclohexane is more stable than the trans isomer
Cis-1,4-dimethylcyclohexane is less stable than the trans isomer
All based on interactions between
substituents and other groups on the ring
YSU
3.12 – Disubstituted Cyclohexanes : Energy Differences
YSU
12
3.13 – Medium and Large Rings
YSU
Cyclohexanes in Biochemistry
YSU
13
3.14 – Polycyclic Ring Systems
adamantane
YSU
3.14 – Polycyclic Ring Systems : Cholesterol
cholesterol
YSU
14
3.14 – Bicyclic Ring Systems
Bicyclobutane
Bicyclo[2.1.0]pentane
Bicyclo[3.2.0]heptane
Bicyclo[4.1.0]heptane
Bicyclo[2.2.2]octane
Bicyclo[4.2.2]decane
YSU
3.15 – Heterocyclic Compounds
tetrahydrofuran
pyrrolidine
piperidine
indole
YSU
15
3.15 – Heterocyclic Compounds
morphine
librium
ritilin
YSU
3.15 – Heterocyclic in Biological Systems
D‐Glucose
YSU
16
Organic Chemistry : The Functional Group Approach
YSU
Organic Chemistry : The Functional Group Approach
YSU
1
Organic Chemistry : The Functional Group Approach
YSU
Organic Chemistry : The Functional Group Approach
YSU
2
Chapter 4 – Alcohols and Alkyl Halides
Figure 4.2 – Electron density maps of CH3OH and CH3Cl
YSU
Alcohols and Halides in Nature and Medicine
Acetaminophen
Valium
Chloramphenicol YSU
3
Chapter 4 – Alcohols and Alkyl Halides
• Functional class nomenclature
pentyl chloride
cyclohexyl bromide
1-methylethyl iodide
• Substitutive nomenclature
2-bromopentane
3-iodopropane
2-chloro-5-methylheptane
YSU
Chapter 4 – Alcohols and Alkyl Halides
1-pentanol
2-propanol
cyclohexanol
2-pentanol
1-methyl
cyclohexanol
5-methyl-2-heptanol
YSU
4
4.4 – Classes of Alcohols and Alkyl Halides
Primary
(1o)
Secondary
(2o)
Tertiary
(3o)
YSU
4.5 – Bonding in Alcohols and Alkyl Halides
Figure 4.1
YSU
5
4.5 – Bonding in Alcohols and Alkyl Halides
Figure 4.2 – Electron density maps of CH3OH and CH3Cl
YSU
4.6 – Physical Properties : Intermolecular Forces
CH3CH2CH3
CH3CH2F
CH3CH2OH
propane
fluoroethane
ethanol
b.p. -42 oC
-32 oC
78 oC
YSU
6
4.6 – Physical Properties : Intermolecular Forces
Figure 4.4
YSU
4.6 – Physical Properties : Intermolecular Forces
Figure 4.5
YSU
7
4.6 – Physical Properties : Water-solubility of Alcohols
Alkyl halides are generally insoluble in water (useful in lab)
YSU
4.6 – Physical Properties : Water-solubility of Alcohols
Solubility is a balance between polar and non-polar
characteristics
YSU
8
4.6 – Physical Properties : Water-solubility of Alcohols

Cholesterol – non-polar alcohol

Limited solubility in water

Precipitates when to concentrated

Results in gallstones
Biochemistry involves a delicate balance of
“like dissolves like”
YSU
4.7 – Preparation of Alkyl Halides from Alcohols and H-X
Lab Conditions:
YSU
9
4.8 – Mechanism of Alkyl Halide Formation
Mechanism – a description of how bonds are formed and/or broken when
converting starting materials (left hand side) to products (right hand side)

Usually involves solvents and reagents, sometimes catalysts

Curved arrows are used to describe the chemical changes
YSU
4.8 – Reaction of a Tertiary Alcohol with H-Cl
Look for chemical changes – which bonds are formed or broken?

learn the outcome of reaction in order to get going quickly

recognize the nature of the organic substrate (1o, 2o, 3o?)

be aware of the reaction conditions (acidic, basic, neutral?)
YSU
10
4.8 – Reaction of a Tertiary Alcohol with H-Cl
YSU
4.8 – Energetic Description of Mechanism: Protonation
Figure 4.6
YSU
11
4.8 – Energetic Description of Mechanism: Dissociation
Figure 4.7
YSU
4.8 – Energetic Description of Mechanism: Association
Figure 4.9
YSU
12
4.9 – Full Mechanism : Pushing Curved Arrows
YSU
4.9 – Full Mechanism : Showing Energy Changes
Figure 4.11
YSU
13
4.10 – Carbocation Structure and Stability
Figure 4.8
YSU
4.10 – Carbocation Structure and Stability
Figure 4.15
Hyperconjugation – the donation of electron density
from adjacent single bonds
YSU
14
4.10 – Relative Carbocation Stability
Figure 4.12
YSU
4.10 – Relative Carbocation Stability
Related to the stability of the intermediate carbocation:
YSU
15
4.11 – Relative Rates of Reaction with H-X
Figure 4.16
Rate-determining step involves formation of carbocation
YSU
4.12 – Reaction Methyl and 1o Alcohols with H-X : SN2
Same bonds are formed and broken as in 3o case, however;

CH3 and 1o carbon cannot generate a stabilized carbocation

kinetic studies show the rate-determining step is bimolecular

sequence of bond-forming/breaking events must be different
YSU
16
4.12 – Reaction Methyl and 1o Alcohols with H-X : SN2
Alternative pathway for alcohols that
cannot form a good carbocation
YSU
4.12 – Energy Profile for SN2
YSU
17
4.14 – Other Methods for Converting ROH to RX

Convenient way to halogenate a 1o or 2o alcohol

Avoids use of strong acids such as HCl or HBr

Via SN2 mechanism at 1o and CH3 groups
YSU
4.15 – Free Radical Substitution of Alkanes
heterolytic
Possible modes of
bond cleavage
homolytic
YSU
18
4.16 – Free Radical Halogenation of Methane
YSU
4.17 – Structure and Stability of Free Radicals
Figure 4.17 – Bonding models for methyl radical
YSU
19
4.17 – Structure and Stability of Free Radicals

Free radical stability mirrors that of carbocations

Hyperconjugation is the main factor in stability

Experimental evidence that radicals are flat (sp2)
YSU
4.17 – Bond Dissociation Energies (BDE)
YSU
20
4.17 – Bond Dissociation Energies (BDE)
104 58 83.5 103
YSU
4.18 – Mechanism for Free Radical Substitution of Methane
YSU
21
4.18 – Mechanism for Free Radical Substitution of Methane
YSU
4.18 – Mechanism for Free Radical Substitution of Methane
YSU
22
4.18 – Mechanism for Free Radical Substitution of Methane
YSU
4.19 – Free Radical Halogenation of Higher Alkanes
Radical abstraction of H is selective since the stability of the ensuing radical is reflected in the transition state achieved during abstraction.

Cl
H

Cl

CH 2CH 2CH2CH3
H

CHCH2CH3
CH3
Lower energy radical, formed faster
YSU
23
4.19 – Free Radical Halogenation of Higher Alkanes
Figure 4.16
YSU
4.19 – Br Radical is More Selective than Cl Radical
Consider propagation steps – endothermic with Br·, exothermic with Cl·
YSU
24
4.19 – Br Radical is More Selective than Cl Radical
Chlorination – early TS
looks less like radical
Bromination – late TS
looks a lot like radical
YSU
25
Organic Chemistry : The Functional Group Approach
YSU
Organic Chemistry : The Functional Group Approach
YSU
1
Organic Chemistry : The Functional Group Approach
YSU
Chapter 5 – Structure and Preparation of Alkenes
O
OH
Arachidonic acid
Vitamin A
Vinyl chloride
YSU
2
Chapter 5 – Structure and Properties of Alkenes
Double bond - now dealing with sp2 hybrid carbon
Figure 5.1 – Different representations of the C=C motif
YSU
5.1 – Structure and Nomenclature of Alkenes
1-butene
2,3-dimethyl-2butene
1-hexene
6-bromo-3propyl-1-hexene
2-methyl-2-hexene
5-methyl-4-hexen-1-ol
YSU
3
5.1 – Common Alkene Substituents
vinyl
allyl
isopropenyl
Vinyl
chloride
Allyl
chloride
Isopropenyl
chloride
YSU
5.1 – Cycloalkenes : Structure and Nomenclature
Br
Cl
cyclohexene
1-chlorocyclopentene
3-bromocyclooctene
OH
4,4-dimethylcyclononene
(E)-cyclodec-3enol
(Z)-cyclododecene
YSU
4
5.2 – Structure and Bonding in Ethylene
Double bond - now dealing with sp2 hybrid carbon
Figure 5.1 – Different representations of the C=C motif
YSU
5.3-5.4 – Cis/Trans Isomerism in Alkenes
1-butene
2-methylpropene
cis-2-butene
trans-2-butene
cis alkene (Z)
trans alkene – (E)
See Table 5.1 for priority rules
YSU
5
Interconversion of Cis- and Trans-2-butene
YSU
5.5-5.6 – Heats of combustion of isomeric C4H8 alkenes
Figure 5.3
YSU
6
5.5-5.6 – Relative Stabilities of Regioisomeric Alkenes
Generally, the more substituted an alkene, the more stable
Figure 5.2 – Inductive effect of alkyl groups contributing to alkene stability
YSU
Molecular Models of cis-2-Butene and trans-2-Butene
Figure 5.4
YSU
7
5.7 – Cycloalkenes : Trans Not Always More Stable Than Cis
H
H
H
H
Cis-cycloheptene and trans-cycloheptene
C-12 cis and trans ~ equal in energy
YSU
5.8 – Preparation of Alkenes : Elimination Reactions
Involves loss of atoms or groups from adjacent carbons
X often = H; Y = good leaving group
YSU
8
5.8 – Preparation of Alkenes : Elimination Reactions
Involves loss of atoms or groups from adjacent carbons
X often = H; Y = good leaving group
YSU
5.9-5.10 – Zaitsev Rule : Regioselectivity
Dehydration usually results in more highly substituted alkene
being major product - Zaitsev rule (regioselectivity)
YSU
9
5.10 – Zaitsev Rule : Regioselectivity
HO CH3
CH3
CH2
+
H
+
OH
H+
+
YSU
5.11 – Stereoselectivity in Alcohol Dehydration
One stereoisomer is usually favoured in dehydrations
When cis and trans isomers are possible in this reaction and
the more stable isomer is usually formed in higher yield
YSU
10
5.12 – Acid-catalyzed Alcohol Dehydration : E1
YSU
5.13 – Carbocation Rearrangements in E1 Reactions
Secondary cation rearranges to tertiary
YSU
11
5.13 – Orbital Representation of Methyl Migration
Figure 5.6
YSU
5.13 – Hydride Shifts to More Stable Carbocations
H2SO4,
OH
"
H
H
H
H
H
C
C
C
C
H
H
H
H
1- butene
trans-2-butene
cis-2-butene
12%
56%
32%
"
H
H
H
H
C
C
C
C
H
H
H
H
H
YSU
12
5.14 – Dehydrohalogenation : Elimination with loss of H-X
Zaitsev rule followed for regioisomers when a small base
such as NaOCH3, NaOCH2CH3 is used.
Trans usually favoured over cis.
YSU
5.15 – The E2 Mechanism : Bimolecular Elimination

Reaction is concerted

Rate depends on [base][alkyl halide] i.e. Bimolecular - E2

Bond-forming & bond-breaking events all occur at the same time
YSU
13
5.15 – The E2 Mechanism : Bimolecular Elimination
YSU
5.16 – Anti Elimination Faster Than Syn Elimination
YSU
14
Conformations of cis- and trans-4-t-Butylcyclohexylbromide
YSU
Favourable Conformations for Fast Elimination
E2 Elimination usually faster when H and leaving group are
anti periplanar as opposed to syn periplanar.
YSU
15
5.17 – Kinetic Isotope Effects and the E2 Mechanism
The C‐D bond is a little bit
stronger than C‐H
Breaking of C‐D is slower
and, if this occurs in the
R.D.S., a kinetic isotope
effect (k.i.e.) is observed:
k.i.e. = (KH/KD)
Typically 3‐8 if the event occurs in the R.D.S. of a reaction, e.g. E2
YSU
5.18 – Different Halide Elimination Mechanism : E1
CH3CH2OH
+
heat
Br
2-methyl-1-butene
2-methyl-2-butene
25%
75%
CH3CH2OH
H
H
CH3CH2OH
YSU
16
Organic Chemistry : The Functional Group Approach
YSU
Organic Chemistry : The Functional Group Approach
YSU
1
Organic Chemistry : The Functional Group Approach
YSU
Chapter 6 – Addition Reactions of Alkenes
Crixivan® (Indinavir, Merck & Co.) protease inhibitor for HIV YSU
2
Chapter 6 – Addition Reactions of Alkenes
Involves addition of atoms or groups to adjacent carbons X often = H; Y = good nucleophile
Examples of both stepwise and concerted mechanisms
YSU
6.1 – Hydrogenation of Alkenes
Needs a precious metal catalyst such as Pt or Pd
(Not covering Mechanism 6.1)
YSU
3
6.1 – Hydrogenation of Alkenes
YSU
6.2 Heats of Hydrogenation of Isomeric C4H8 Alkenes
(KJ/mol)
Figure 6.1
YSU
4
6.2 – Heats of Hydrogenation of Alkenes
YSU
6.3 – Stereochemistry of Alkene Hydrogenation
H atoms have added to the same face of the alkene ‐ syn addition
YSU
5
6.3 – Stereochemistry of Alkene Hydrogenation
Figure 6.2
YSU
6.4 – Electrophilic Addition of Hydrogen Halides to Alkenes
Stronger acids react faster : H‐I > H‐Br > H‐Cl >> H‐F
Slow step of reaction is protonation to give intermediate carbocation
YSU
6
6.4 – Electrophilic Addition Mechanism
YSU
6.4 – Electrophilic Addition Mechanism
YSU
7
6.5 – Regioselectivity in Electrophilic Addition
Since the reaction involves formation of cations, the major product
arises from the more stablized intermediate carbocation
Markovnikov’s Rule
YSU
6.6 – Mechanistic Basis for Markovnikov's rule
Figure 6.4
YSU
8
6.6 – Examples of H-X Additions to Alkenes
YSU
6.7 – Cation Rearrangements in H-X Addition to Alkenes
2o cation undergoes intramolecular rearrangement
to more stable 3o cation
YSU
9
6.8 – Electrophilic Addition of Sulfuric Acid

Outcome depends upon concentration of H2SO4 used

Sulfonate ester isolated using concentrated H2SO4

Alcohol isolated directly with dilute H2SO4

Markovnikoff Rule applies for nonsymmetrical alkenes
YSU
6.9 – Acid-catalyzed Hydration of Alkenes
Note the Markovnikoff regioselectivity


Reaction is exothermic; products favoured (stronger single bonds vs. pi bond)
Use of catalytic acid can avoid decomposition of more complicated substrates
YSU
10
6.9 – Acid-catalyzed Hydration of Alkenes
YSU
6.9 – Acid-catalyzed Hydration of Alkenes
YSU
11
6.9 – Acid-catalyzed Hydration of Alkenes
Related to relative stabilities of intermediate carbocations
YSU
6.10 – Thermodynamics of Addition-Elimination
If the alkene is less stable, how can this reaction be useful? Recall: G = H ‐ TS
YSU
12
6.10 – Thermodynamics of Addition-Elimination
How do you get one product over the other?

In dehydration (elimination) – remove alkene, run at high temperature

In hydration (addition) – use excess water, run at low temperature

Taking advantage of both Le Châtelier’s principle and G = H ‐ TS
YSU
6.11 – Hydroboration - Oxidation of Alkenes
Addition
Oxidation
YSU
13
6.11 – Hydroboration – Modern Reagents
H
H
B
B
“parachute borane”
H.C. Brown
YSU
6.11 – Hydroboration – Regioselective and Stereoselective
Two possible transition states for concerted addition of H‐BR2
to an unsymmetrical alkene
YSU
14
6.12 – Hydroboration – Regioselective and Stereoselective
Left T.S. is more favourable since it avoids the larger CH3
groups and the BR2 group interacting – results in regioselectivity
YSU
6.12 – Stereochemistry of Hydroboration
Addition of H‐BR2 is a concerted syn addition – evidence for mechanism
YSU
15
6.12 – Stereochemistry of Hydroboration
CH3 H B
CH3
H
NaOH/H2O2
CH3
H
B
OH
Oxidation step retains the stereochemistry from first step
Important evidence for the mechanism being concerted
YSU
6.12 – Stereochemistry of Hydroboration
YSU
16
6.13 – Mechanism of Hydroboration - Oxidation
CH3
H
1. H-BR2, THF
CH3
2. NaOH, H2O2
OH
Step 1 Syn Addition
R
B
R
H
R2B
H
H
H
HH
H
H
H
H
YSU
6.13 – Mechanism of Hydroboration - Oxidation
Step 2 Oxidation
H O O H
-H2O
+
H O O
NaOH
H O O
R2B
H
R2B
O
Na
O H
R2B
O
H
- OH
CH3
CH3
CH3
H
OH
CH3
OH H
then hydrolyze
CH3
YSU
17
6.14-6.16 – Addition of Halogens - Anti addition via cations
No syn addition product formed
Anti addition outcome is easily seen in cycles
Stepwise or concerted mechanism?
YSU
6.14-6.16 – Addition of Halogens - Anti addition via cations
Br Br
Br
or
Br
Br
Br
???
Two possibilities for stepwise mechanism, second explains stereochemistry
YSU
18
6.17 – Addition of “X-OH” : Halohydrin Formation
Br2
Br
in H2O
(- H+)
OH2
Br
OH
Reaction can also result in regioselective outcome:
YSU
6.18 – Free Radical Addition of H-Br to Alkenes
Peroxides = HOOH, ROOR (R = Ph, t‐Bu, etc.)
YSU
19
6.18 – Free Radical Addition of H-Br to Alkenes
YSU
6.19 – Epoxides from Alkenes
Hydrohalogenation followed by intramolecular substitution:
Reaction of an alkene with a peroxy acid:
YSU
20
6.19 – Epoxides : Essential Synthetic Intermediates
Crixivan® (Indinavir, Merck & Co.) protease inhibitor for HIV YSU
6.20 – Ozonolysis of Alkenes : Cleavage of the Double Bond
CH3
CH3
H
H3C
CH3
1. O3
O
O
H
CH3
H3C
O
O
H3C
O
2. Zn, H2O
CH3
H3C
H3C
CH3
O
O
O
H3C
malozonide
ozonide
YSU
21
6.21 – Reactions of Alkenes with Alkenes : Polymerization
H
H
200oC
H
or peroxides
H
ethylene
polyethylene
F
F
FF
FF
FF
F
FF
F
tetrafluoroethylene
CO2CH3
H
FF
FF
teflon
o
200 C
CH3O2C
CO2CH3
CO2CH3
CH3
H
or peroxides
ethylene
plexiglass
YSU
6.21 – Radical Polymerization
YSU
22
Synthesis in Organic Chemistry
Br
OH
H
H
1. B2H6
2. NaOH, H2O2
HBr
peroxides
Br
(also BrOH)
H2, Pd
Br
H
base (E2)
neutral (E1)
H
HBr (addition)
Br2
H+, H2O
H
or hv
Br
H3PO4
or H2SO4
heat
H2O (SN1)
OH
YSU
23
Chapter 7 - Stereochemistry
Enantiomers of bromochlorofluoromethane
Non-superimposable mirror images
Enantiomers
YSU
Biologically-active Chiral Molecules
YSU
1
Chirality in the Pharmacutical Industry
> $100 billion sales worldwide
Account for 32% of total drug sales
YSU
7.2 – The Chirality Center : Stereoisomerism
Carbon atom here is asymmetric
C is a stereogenic center
YSU
2
7.3 – Symmetry in Achiral Structures
Achiral i.e. not chiral
Mirror images of chlorodifluoromethane are superimposable
Figure 7.2
YSU
7.4 – Measurement of Optical Activity
Typical polarimeter setup : []D = 100 x (rotation)/(cell length) x (conc’n)
YSU
3
Which molecules contain chiral (stereogenic) centers?
The stereogenic C must have 4 different groups attached
YSU
7.5 – Absolute and Relative Configuration
Absolute Configuration – Actual arrangement of substituents in space
(+)‐2‐butanol and (‐)‐2‐butanol, but which is which?
Relative Configuration ‐ Configuration relative to another compound.
Pre‐1951, compounds could be related to each other but the absolute configuration was not able to be determined.
YSU
4
7.6 – Nomenclature : Use of the Cahn-Ingold-Prelog System
S enantiomer
R enantiomer
R ‐ Rectus ‐ the clockwise arrangement of groups
S ‐ Sinestre ‐ the counterclockwise arrangement of groups
YSU
7.6 – Nomenclature : Use of the Cahn-Ingold-Prelog System
YSU
5
7.7 – Fischer Projection Formula
Figure 7.5
YSU
7.8 – Enantiomers
• same physical properties except rotation of plane polarized light
• one enantiomer positive rotation (+) other negative rotation (‐)
YSU
6
7.9 – Biologically-active Chiral Molecules
YSU
7.10 – Reactions That Create a Chirality Center
YSU
7
7.11 – Chiral Molecules With Two Chirality Centers
Figure 7.7
YSU
7.11 – Representations of (2R, 3R)-Dihydroxybutanoic acid
Conversion of “zig‐zag” picture to Fischer projection
Figure 7.8
All the same molecule:
(a) and (b) differ only by bond rotation
(b) leads to correct Fischer projection
YSU
8
7.11 – Chiral Molecules With Two Chirality Centers
Important stereochemical labels later, particularly in carbohydrate (sugar) chemistry and biochemistry
YSU
7.11 – Chiral Molecules With Two Chirality Centers
Applies to other cycles, including cyclohexane; increases the molecular diversity possible using simple structures
YSU
9
7.12 – Achiral Molecules With Two Chirality Centers
Figure 7.9
YSU
7.12 – Achiral Molecules : Meso-2,3-butanediol
Figure 7.10
YSU
10
7.13 – Stereogenic Centers in Cholic Acid
Figure 7.11
YSU
7.14 – Reactions That Produce Diastereomers
Figure 7.12
YSU
11
7.15 – Resolution of a Chiral Substance into its Enantiomers
Figure 7.13
YSU
12
Organic Chemistry : The Functional Group Approach
YSU
Organic Chemistry : The Functional Group Approach
YSU
1
Organic Chemistry : The Functional Group Approach
YSU
Chapter 8 – Nucleophilic Substitution at sp3 Carbon
• nucleophile is a Lewis base (electron-pair donor)
• often negatively charged and used as Na+ or K+ salt
• substrate is usually an alkyl halide
YSU
2
8.1 – Functional Group Transformation by SN2
Table 8.1 Examples of Nucleophilic Substitution
Alkoxide ion as nucleophile
gives an ether
• Referred to as the Williamson ether synthesis
• Limited to primary alkyl halides
• Run in solvents such as diethyl ether and THF
YSU
8.1 – Carboxylate Anion as Nucleophile
gives an ester
• Not very useful – carboxylates are poor nucleophiles
• Limited to primary alkyl halides
• Run in solvents such as diethyl ether and THF
• Better ways of forming esters later in 3720
YSU
3
8.1 – Cyanide and Azide Anions as Nucleophile
YSU
8.1 – Halide Anions as Nucleophile : Finkelstein Reaction
• NaI is soluble in acetone, NaCl and NaBr are not
• NaCl and NaBr precipitate from reaction mixture
• Drives equilibrium to iodide (Le Châtelier’s principle)
YSU
4
8.2 – Relative Reactivity of Halide Leaving Groups
• Halides are generally very good leaving groups
• I‐ better than Br‐ which is better than Cl‐
F
Cl
I
Br
F‐ is not used as a leaving group
YSU
8.3 – The SN2 Mechanism of Nucleophilic Substitution
Example:
CH3Cl + HO –
CH3OH + Cl –
rate = k[CH3Cl][HO – ]
inference: rate-determining step is bimolecular
YSU
5
Inversion of Configuration During SN2 Reaction
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Inversion of Configuration During SN2 Reaction
http://www.bluffton.edu/~bergerd/classes/cem221/sn‐e/SN2.gif
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8.4 – Steric Effects in Substitution (SN2) Reactions
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Relative Rates of Reaction of Primary Alkyl Bromides
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Relative Rates of Reaction of Primary Alkyl Bromides
Local steric environment has a dramatic effect on reaction rates
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8.5 – Nucleophiles and Nucleophilicity
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8.6 – The SN1 Reaction Revisited
CH3
Br
H3C
CH3
H2O
CH3
H3C
OH
CH3
Tertiary system ‐ favours SN1 ‐ carbocation possible
Carbocation will be the electrophile
Water will be the nucleophile
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Solvolysis of t-BuBr with Water
Figure 8.5
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8.7 – Relative Rates of Reaction by the SN1 Pathway
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8.8 – Stereochemical Changes in SN1 Reactions
Figure 8.6
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8.9 – Carbocation Rearrangements Also Possible in SN1
• Look for change in the product skeleton relative to substrate.
• Rearrangement (alkyl or hydride shift) to generate a more
stable carbocation.
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8.10 – Choice of Solvent for SN1 is Important
Polar solvents (high dielectric constant) will help
stabilize ionic intermediates
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8.10 – Polar Solvent can Stabilize Transition States
Figure 8.7
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8.10 – Choice of Solvent Important in SN2
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12
Solvation of a Chloride by Ion-dipole
Figure 8.3
Choice of solvent is important for SN2 ‐ polar aprotic
used most often
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8.11 – Substitution vs. Elimination : SN2 vs. E2
NaOCH2CH3
Br
+
CH3CH2OH, 55oC
9%
NaOCH2CH3
Br
91%
+
CH3CH2OH, 55oC
87%
OCH2CH3
OCH2CH3
13%
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8.11 – Substitution vs. Elimination : SN2 vs. E2
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8.12 – Sulfonate Ester Leaving Groups
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14
Organic Chemistry : The Functional Group Approach
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Organic Chemistry : The Functional Group Approach
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1
Organic Chemistry : The Functional Group Approach
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Organic Chemistry : The Functional Group Approach
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2
Chapter 9 – Alkynes : sp Hybrid Carbon
Histrionicotoxin
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Organic Chemistry – Directional Platforms
Tetrahedral
Trigonal planar
Linear
(4 valent)
(4 valent)
(2 valent)
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3
9.1 : Sources of Alkynes – Acetylene (Cracking of Hydrocarbons)
Acetylene (sp,
linear)
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Click Chemistry – Bioorganic Applications
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Click Chemistry – Bioorganic Applications
Bertozzi et. al. U.C. Berkeley
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9.2-9.3 – Nomenclature and Physical Properties
Alkynes are typically non-polar and insoluble in water
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9.4 – Structure and Bonding in Alkynes
Figure 9.2
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9.5 – Acidity of Acetylene and Terminal Alkynes
Choice of base determines extent of deprotonation
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9.6 – Acetylide Anions as Nucleophiles in SN2 Reactions
CH3CH2Br
CH3 C C
Na
CH3 C C CH2CH3
THF
1. NaNH2, THF
Na
1.
CH3 C C
2.
CH3 C C CH3
CH3 C C H
2. CH3Br, THF
Strong base required for complete deprotonation
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9.12 – Addition of H2O to an Alkyne – Hydration
H
O
O
CH3 C CH2CH3
H+, H2O
CH3 C C CH3
H
H
H
H
O
H
H
CH3 C C CH3
H
O
H
CH3 C C CH3
H
O
CH3 C CH2CH3
H
H
O
H
O
H
H
O
CH3 C C CH3
H
O
CH3 C CH2CH3
H
H
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7
9.12 – Keto-Enol Tautomerism
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Chapter 9 – Alkynes
Not covering
9.7 – 9.14
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8
Organic Chemistry : The Functional Group Approach
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Organic Chemistry : The Functional Group Approach
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1
Organic Chemistry : The Functional Group Approach
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Organic Chemistry : The Functional Group Approach
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2
Organic Chemistry : The Functional Group Approach
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Chapter 10 – Conjugation in Dienes and Allylic Systems
Arachidonic acid
Vitamin A
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10.1 – The Allyl Group
Typical Allylic Systems
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10.2 – Allyllic Carbocations
Figure 10.1
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10.3 – SN1 Reactions of Allylic Halides
Allylic system reacts 123 times faster
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10.3 – SN1 Reactions of Allylic Halides
via
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5
10.4 – SN2 Reactions of Allylic Halides
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10.5 – Allylic Free Radicals
Figure 10.2
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10.6 – Radical Halogenation at Allylic Positions is Possible
Usual radical process steps are involved;
Initiation, Propagation and Termination
Intermediate radical is stabilized by resonance
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10.7 – Allylic Anions
Figure 10.4
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10.8 – Classes of Dienes
1,4-pentadiene
1,3-pentadiene
Figure 10.2
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10.9 – Relative Stabilities of Dienes
Figure 10.5
Conjugated diene
~ 15 kJ/mol more
stable
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10.10 – Bonding in Conjugated Dienes
1,4-pentadiene
1,3-pentadiene
Figure 10.2
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10.10 – Conformations of Dienes
Conformers, not isomers
Conformers are interconvertible
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10.10 – Conformations of Dienes
Some trapped
as s-cis
O
Some trapped
as s-trans
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10.10 – Conformations of 1,3-Butadiene
Figure 10.5
The s‐cis and s‐trans
conformers are interconvertible with an ~3.9 kcal/mol barrier
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10.11 – Bonding in 1,2-Propadiene (Allene)
Figure 10.6
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10.11 – Bonding in 1,2-Propadiene (Allene)
Figure 10.6
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10.12 – Preparation of Dienes
Conjugation preferred
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10.13 – Addition of HBr to 1,3-Butadiene
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Thermodynamic versus Kinetic Control
Addition of HBr is reversible so
at higher temps the equilibrium
outcome will favour the more
stable product. Lower temp.
reduces ability of products to
revert to cation so the kinetic
outcome is then favoured.
Figure 10.8
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10.15 – The Diels-Alder Cycloaddition Reaction
R
solvent,
R
or Lewis acid, RT
Diene Dienophile
Lowest unoccupied molecular
orbital of diene
Highest occupied molecular
orbital of dienophile
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10.15 – The Diels-Alder Cycloaddition Reaction
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10.15 – The Diels-Alder Cycloaddition Reaction
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10.15 – The Diels-Alder Cycloaddition Reaction
Total Synthesis of Minfiensine
MacMillan, Jones, Simmons. JACS, 2009; Discussed at www.totallysynthetic.com
Total Synthesis of Vinigrol
Baran, Maimone, Shi, Ashida. JACS, 2009; Discussed at www.totallysynthetic.com
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Chapter 10 – Conjugated Systems
Not covering
10.16
10.17
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15
Organic Chemistry : The Functional Group Approach
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Organic Chemistry : The Functional Group Approach
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1
Organic Chemistry : The Functional Group Approach
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Organic Chemistry : The Functional Group Approach
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2
Organic Chemistry : The Functional Group Approach
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Chapter 11 – Arenes and Aromaticity
O
OH
Ibuprofen
Codeine
Sildenafil
Phenylalanine
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11.1 – Increasing Unsaturation in 6-Membered Rings
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11.2 – Evidence of Structure for Benzene
Kekule (1866) – two rapidly interconverting isomers?
all C‐C bonds are the same length, all H’s are equivalent
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11.2 – Evidence of Structure for Benzene
Robinson (1920) ‐ the two Kekule forms are resonance contributors
all C‐C bonds are the same length, all H’s are equivalent
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11.2 – Evidence of Structure for Benzene
Robinson depiction : “Aromatic Sextet”
all C‐C bonds are the same length, all H’s are equivalent
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11.3 Resonance Energy Estimate from H Hydrogenation
Benzene is a lot more stable than “cyclohexatriene”
3 alkenes + 3 H2 = 360 KJ per mol
Benzene + 3 H2 = 208 KJ per mol
Difference = resonance energy
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11.4 – Representations of Benzene
Figure 11.3
i.e. each carbon experiences the same electron density, the six pi electrons are delocalized over the entire molecule
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11.4 – Molecular Orbitals of Benzene
Figure 11.4
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11.5 – Molecular Orbitals of Benzene
Figure 11.4
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11.6 – Nomenclature of Substituted Benzenes
Many have common names, however IUPAC systematic names often easier to work out
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11.6 – Nomenclature of Disubstituted Benzenes
CH3
Br
F
Br
CH3
NO2
F
NH2
CH3
Br
CH2H3
CH3
CH3
Can use numbering or o, m, p
nomenclature systems
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11.7 – Polycyclic Aromatic Systems
Naphthalene
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11.8 – Physical Properties of Arenes
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11.9 – Physical Properties of Arenes
Chapter 11 : Reactions at the Benzylic position
Chapter 12 : Reactions at the Benzene ring carbons
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Chapter 11 – Arenes and Aromaticity
Not Covering
11.10 The Birch Reduction
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11.11 – Free-Radical Halogenation of Alkylbenzenes
C
H
C
H
H
C H
H
H
H
C H
H
H
H
+
H
H = 91 kcal/mol
+
H
H = 88 kcal/mol
+
H
H = 85 kcal/mol
H
H C H
H C
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11.11 – Free-Radical Halogenation of Alkylbenzenes
H
H
H C H
H C Br
Br2
(+
HBr)
CCl4, 80 oC
71% yield
Figure 11.9
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11.12 – Oxidation of Alkylbenzenes
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11.13-11.14 – Nucleophilic Substitution in Benzylic Halides
SN2 applies with good nucleophiles on 1o and 2o carbons
SN1 applies with weak nucleophiles – good carbocation
E2 competes with more basic nucleophiles on 2o and 3o
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11.15 – Preparation of Alkenylbenzenes
CH3
CH3
CH3 C Br
C
CH2
NaOCH3
CH3OH
CH3
CH3
CH3 C OH
C
CH2
KHSO4
Cl
heat
Cl
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11.16 – Addition to Alkenylbenzenes
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Chapter 11 – Aromatic Systems
Not Covering
11.17
11.18
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11.18-11-23 – Hückel’s Rule
http://redandr.ca/vm3/Heme.jpg
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11.18-11.23 – Hückel’s Rule
Aromatic = 4n+2  electrons and flat  system
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11.18-11.23 – Hückel’s Rule
Figure 11.12
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11.18-11.23 – Aromatic Ions
Cation is relatively easy to form: 4n + 2 = 6
system capable of being flat
Figure 11.13
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11.18-11.23 – Aromatic Ions
pKa of acid is ~16 since anion is aromatic: 4n + 2 = 6
system capable of being flat
Figure 11.14
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11.23 – Heterocyclic Aromatic Compounds
Figure 11.15
..
N
H
pyrrole
N
..
pyridine
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Click Chemistry – Bioorganic Applications
Bertozzi et. al. U.C. Berkeley
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Click Chemistry – Use of Aromatic Conjugation in vivo
Bertozzi et. al. ACS ChemBiol, 2009, 4, 1068-1072
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