Chemistry 3720 - Organic Chemistry II
Dr. Peter Norris
6014 Ward Beecher
(330) 941-1553
pnorris@ysu.edu
http://www.as.ysu.edu/~pnorris/public_html
Lecture needs:
Carey
Molecular models
Adobe Acrobat
Reader
Web access
Lab needs:
Pavia, Lampman,
Kriz and Engel
Goggles
Lab coat
Bound notebook
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3 7 2 0 We b R e s o u r c e s
http://www.as.ysu.edu/~chemistry
http://www.as.ysu.edu/~pnorris/public_html
(Contains lab and lecture material, problem sets and old exams)
Need the Adobe Acrobat Reader to download printed material, links to the site are on
the web page
Chemistry 3720 page includes practice problems on NMR spectroscopy (Chapter 13)
Message board linked to 3720 home page for asking questions,
especially before exams
http://www.as.ysu.edu/~chem/
http://www.as.ysu.edu/~pnorris/
2
Chemistry Computer Lab
North end of Ward Beecher on the 5th floor
Dell Pentium 4 machines
Hewlett Packard network laserjet printers
Student assistant (?)
All PC’s have MS Office, ChemDraw, ChemSketch, ACD NMR
prediction software, Spartan molecular modeling package,
Netscape Navigator and MS Internet Explorer
Open 9-5 Mon through Fri (see lab door for schedule)
Class Requirements (see s yllabus)
3720 Lecture:
3 term exams, 100 points each
1 Final exam, 200 points
No dropped tests
3720 Lab:
100 points total. Must pass lab (>60%)
in order to pass 3720/3720L
Misconduct:
Any copying or other forms of
cheating will be dealt with severely
Why a year of Organic Chemistry?
Organic
Chemistry
chemical
synthesis
New
Materials
materials
chemistry
New
Compounds
medicinal
chemistry
New
Medicines
Biochemistry
and
Chemical Biology
Nanotech,
Engineering
Proteomics,
Genetics
Pharmacy,
Medicine
3
Chemistry 3719-3720
H
C
H
H
H
~1800 – Organic Chemistry : the chemistry of natural products based
on carbon
2008 – Organic Chemistry : “molecular engineering”
3720 Overview of Chapters
12 Reactions of benzene – electrophilic aromatic substitution
13 Spectroscopy – how do you know what the structure is?
14 C-C bond formation using organometallic compounds
15 Chemistry of alcohols, diols and thiols
16 Chemistry of ethers, epoxides and sulfides
17 Aldehydes and ketones – preparation and uses
18 Enols and enolates in the formation of C-C bonds
19 Carboxylic acids – preparation and uses
20 Nucleophilic acyl substitution
21 Ester enolates – formation and uses in C-C bond formation
22 Chemistry of amines
25 Overview of carbohydrate chemistry
26 Overview of lipid chemistry
27 Overview of amino acid, peptide and protein chemistry
Chapter 12 - Reactions of Benzene - EAS
12.1
Introduction to benzene vs. alkenes
12.2
Mechanistic principles of Electrophilic Aromatic Subsitution
12.3
Nitration of benzene, reduction to aminobenzenes
12.4
Sulfonation of benzene
12.5
Halogenation of benzene
12.6
Friedel-Crafts alkylation of benzene
12.7
Friedel-Crafts alkylation of benzene
12.8
Alkylbenzenes via acylation then reduction
12.9
Rate and regioselectivity in EAS
12.10
Nitration of toluene - rate and regioselectivity
12.11
Nitration of CF3 -benzene - rate and regioselectivity
12.12
Substituent effects in EAS: Activating Substituents
12.13
Substituent effects in EAS: Strongly Deactivating Substituents
12.14
Substituent effects in EAS: Halogens
12.15
Multiple substituent effects in EAS
12.16
Regioselective synthesis of disubstituted aromatic compounds
12.17
12.18
Substitution in Naphthalene
Substitution in heterocyclic aromatic compounds
4
Introduction – Benzene vs. Alkenes
Br Br
Br
no heat
dark
Br
Br Br
no colour change
(no reaction)
no heat
dark
Completely delocalized (6) pi system lends stability (aromatic)
12.2 Mechanistic Principles of EAS
Alkenes react by addition
E
Y
E
E
Y
Y
Benzene reacts by substitution
E
Y
Y
H
E
-H
Y
E
Resonance-stabilized cation
5
General Mechanism of EAS on Benzene
Energy diagram for EAS in benzene
Figure 12.1
Electrophilic Aromatic Substitutions on Benzene
H
HNO 3 , H 2 SO 4
NO 2
12.3 Nitration
H
SO 3H
SO 3 , H 2 SO 4
12.4 Sulfonation
H
Br
Br 2, Fe
12.5 Halogenation
12.6 Friedel-Crafts Alkylation of Benzene
H
CH2CH3
CH3CH2Cl
AlCl3
CH3
H
C CH3
(CH3)3CCl
CH3
AlCl3
H
H3C
Cl
CH3
CH3
C CH3
CH 3
AlCl3
Problems:
Alkyl groups may rearrange during reaction
Products are more reactive than benzene
Uses:
Alkyl benzenes readily oxidized to benzoic acids using KMnO4
6
12.7 Friedel-Crafts Acylation of Benzene
H
O
O
RCCl
C
R
AlCl3
O
H
HC
3
O
O
O
CCH3
CH
3
AlCl3
O
AlCl 3
RCCl
O
RC
R C O
Products react more slowly than benzene - cleaner reaction
No carbocation rearrangements
12.8 Alkylbenzenes via Acylation/Reduction
Zn, HCl
O
C
H H
C
R
(Clemmensen)
R
or
NH2NH2, KOH
heat
(Wolff-Kischner)
O
AlCl3
Cl
Zn, HCl
O
Make the acyl benzene first (clean, high yielding reaction)
Reduce the ketone group down to the methylene (C=O to CH2)
Avoids rearrangement problems, better yields
Aminobenzenes via Nitration/Reduction (not in text)
H
O
N
H
Sn, HCl
N
O
HNO3, H2SO4
NO2
H
Sn, HCl
H
N
H
Make the nitro benzene first, clean high yielding reaction
Reduce the nitro group down to the amine
Difficult to introduce the amino group by other methods
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12.9 Activation and Deactivation by Substituents (Rates)
X
X
HNO 3, H2SO 4
NO2
CF3
0.000025
H
CH3
1.0
25
Relative rates in nitration reaction
now bringing in a second substituent
12.9 Nitration of Toluene vs Nitration of (Trifluoromethyl)benzene
CH3
CH3
HNO3, H2 SO4
CH3
CH3
NO2
+
+
NO2
NO2
63%
3%
34%
CH3 is said to be an ortho/para director (o/p director) - Regioselectivity
CF3
CF3
HNO3, H2SO4
CF3
CF3
NO2
+
+
NO2
NO2
6%
91%
3%
CF3 is said to be a meta director (m director) - Regioselectivity
12.10 Rate and Regioselectivity in Nitration of Toluene
CH3
CH3
HNO3 , H2 SO4
CH3
CH3
NO2
+
+
NO2
NO2
63%
3%
34%
Fig. 12.5 – Energy diagrams for toluene nitration (vs. benzene)
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12.11 Rate and Regioselectivity in Nitration of CF3C6H5
CF3
CF3
HNO3, H2SO4
CF3
CF3
NO2
+
+
NO2
NO2
6%
91%
3%
Fig. 12.6 – Energy diagrams for CF3C6H5 nitration (vs. benzene)
12.12 Substituent Effects – Activating Substituents
General :
all activating groups are o/p directors
halogens are slightly deactivating but are o/p directors
strongly deactivating groups are m directors
Activating Substituents
O
R
HO
alkyl
RO
hydroxyl
RCO
alkoxy
OCH 3
acyloxy
OCH 3
HNO3 , H2 SO4
Example:
OCH 3
NO2
+
NO2
Alkyl groups stabilize carbocation by hyperconjugation
Lone pairs on O (and others like N) stabilize by resonance
12.13 Subst. Effects – Strongly Deactivating Substituents
O
O
O
HC
R C
HO C
aldehyde
ketone
carboxylic acid
O
O
Cl
RO C
C
N
O
HO S
C
ester
acyl chloride
O2 N
O
nitrile
sulfonic acid
NO2
nitro
NO2
Br 2 , Fe
Example:
Br
Second substituent goes meta by default – best carbocation
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12.14 Substituent Effects – Halogens
X
X
X
X = F, Cl, Br
X = F, Cl, Br
Reactivity (i.e. rate) is a balance between inductive effect (EW) and resonance effect
(ED) – larger Cl, Br, I do not push lone pair into pi system as well as F, O, N, which are all
first row (2p)
Example:
Cl
Cl
HNO3, H2 SO4
Cl
Cl
NO2
+
+
NO2
NO2
30%
1%
69%
Regioselectivity - second substituent goes o/p – better carbocations
12.15 Multiple Substituent Effects
CH3
O
H3C
NHCH3
CH3 O
O
O
CH3
NHCH3
Br2, acetic acid
CH 3
Br
AlCl3
Cl
CH3
CH3
Cl
99%
87%
CH3
CH3
CH3
Br
Br2, Fe
NO2
C(CH 3)3
NO2
NO2
CH3
HNO3, H2SO4
C(CH3)3
86%
88%
Interplay between power of directing group and size of substituents
12.16 Regioselective Synthesis of Disubstituted Derivs.
O
O
CH3
O
CH3
CH3
Br
Br
NO2
CO2 H
CH2CH3
Br
NO2
Have to be careful about when to introduce each substituent
Remember – isomers (e.g. o/p mixtures) may be separated
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12.17-12.18 Substitution in Other Aromati c Systems
12.17 Naphthalene
O
CH3
O
O
CH3 CCl
CH3
but not
AlCl3
90%
12.18 Heterocycles
SO3H
SO3, H 2 SO4
N
HgSO4 , 230 o C
O
H3C
N
O
O
CH 3
CH3
O
BF 3
O
O
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