CHEM 32 - CHAPTER REVIEW
…. not everything you need to
know, but at least a summary of
the beginning of what you need
to know….
Chapter 14: Delocalized !-Systems
Chapter 14:
R
R
Z
Z
! or Lewis Acid
+
Delocalized !-Systems
R
Z
R
! or Lewis Acid
Z
! or Lewis Acid
Z
+
Z
+
R
R
R
R
Z
Z
! or Lewis Acid
+
R'
R'
R
R
Z
Z
! or Lewis Acid
+
R'
R'
R
R
Z
Z
! or Lewis Acid
R
+
Z
R'
R'
Chapter 15: Electrophilic Aromatic Substitution
The main criteria for aromaticity are:
- high chemical stability
- preference of substitution over addition reactions
- ability to sustain an induced ring current ("NMR!)
- meet Hückel' s rule [4n+2]
R'
Chapter 15: Electrophilic Aromatic Substitution
The mechanism of electrophilic aromatic
substitution involves (a) the reaction between
the aromatic ring and the electrophile to yield
a pentadienyl cation intermediate (the complex), and, (b) the loss of a proton from
the pentadienyl cation to r egenerate the
aromatic ring system.
Chapter 16: Substituent Effects on Electrophilic Aromatic Substitution
Chapter 16: Substituent Effects on Electrophilic Aromatic Substitution
Chapter 17: Aldehydes & Ketones
Chapter 17: Aldehydes & Ketones
Reactant
Reagent
O
H2O
R
Intermediate
Product
HO OH
R
R'
“
R”OH, H+
“
HOCH2CH2OH, H+
HO OR"
R
R' hydrate
R"O OR"
R' hemiacetal
R
R' acetal/ketal
“
“
NaCN, H+
“
NaHSO3
“
H2NR”
HO NHR"
“
HNR*R”
HO NR*R"
“
HONH2
HO NHOH
“
H2NNHR”
HO NH-NHR"
O
O
R
R'
HO CN
R
R' cyanohydrin
HO SO3Na
R
R
R
“
R'
R
R
R'
enamine
R
R'
oxime
N-NHR"
R'
R
R'
imine
NOH
R
O PPh3
Ph3P CR*R"
R'
NR*R"
R'
R
bisulfite adduct
NR"
R'
R
R'
R'
hydrazone
R"
R*
R
R'
R*
R"
alkene
oxaphosphetane
The Baeyer-Villiger reaction converts ketones to esters. Migratory aptitude increases in the
series Me < primary alkyl < phenyl, secondary alkyl < tertiary.
Chapter 18: Enols & Enones
R2C
C
H
O
O
R2C
R'
C
R'
H
! proton is relatively
acidic (pKa!20); it can
be removed by bases
! carbon atom of enol
is nucleophilic; it attacks
electrophilic reagents
carbonyl group is electrophilic; nucleophilic reagents
add to carbonyl group
-Halogenation. Halogens react with
aldehydes and ketones by substitution; An acid catalyst (or base) increases the rate of enolization
(enolate formation), which is the ratedetermining step. T he reaction of a
methyl ketone with a halogen in base
is known as the haloform reaction.
Once one of the -H's is replaced by a
halogen atom, the remaining H's a re
more acidic and are more easily
substituted. C,C-bond cleavage is
facilitated by the e--withdrawing effect
of the halogens.
O
CH3CO2H, Br2
O
O
H
O
Br
O
NaOH, H2O, Br2
Br
O
O
Br
O
Br
Br
Br
Br
Br
H
Br
Br
O
+
HO
Chapter 18: Enols & Enones
O
RCH2
C
HO
NaOCH2CH3
R'
HOCH2CH3
(2 equiv)
RCH2
O
R'
R'
R
R'
NaOCH2CH3
HOCH2CH3
-H2O
O
RCH2
R'
R
Li
O
LDA
O
O
CH3CH2CHO
OLi
THF, -78° C
CH2CH3
O
H2O
OH
(workup)
85%
CH2CH3
NaOCH2CH3,
CH3CH2OH
+
46%
O
O
(MVK)
O
Chapter 19: Carboxylic Acids
O
O
O
O
>
R
Cl
R
O
R
O
O
>
>
R
OR'
>
R
OH
R
O
NH2
>
R
reactivity
O
RO
O
O
Cl
chloroformate
RO
OR
carbonate
R2N
O
NR2
urea
R2N
OR'
carbamate/urethane
O
-
Chapter 19: Carboxylic Acids
Reagents for the interconversion of carboxylic acid derivatives:
O
O
O
O
O
O
O
R-C!N
R
Cl
R
O
R
R
OR'
R
OH
R
NR2
R
O
O
O
R
Cl
O
O
-
R
O
R'OH, py
H 2O
R2NH, py
H2O, OH-
-
-
-
R'OH, py
H 2O
R2NH, py
H2O, OH-
-
OR"
-
-
R'OH, H+/B-
H2O, H3O+
R2NH
H2O, OH-
-
OH
SOCl2
-
DCC, R2NH
OH-
-
NR2
-
-
H2O, H3O+
-
O
-
-
H 3 O+
-
R-C!N
-
R'OH, H+,H2O
H2O, H+
H2O, H+
R
O
R
O
R
O
R
, -H2O
R'OH, H+,
O
R
-
O
R
OH-,
SOCl2
O
R
Cl
-
OH-,
-
Chapter 20: Carboxylic Acids & Mass Spectroscopy
O
The Hofmann rearrangement involves:
R
N
R-N=C=O, isocyanates, and
H
N
OH
nitrenes;
R
carbamic acids
O
Chemistry of carboxylic acid derivatives:
Chapter
20:
Carboxylic
Acids &
Mass
Spectroscopy
O
O
O
O
O
O
O
R-C!N
R
LAH
Cl
RCH2 OH
R
O
R
RCH2 OH
R
OR"
RCH2 OH,
R
OH
R
NR2
R
O
RCH2 OH
RCH2 NR2
RCH2 OH
RCH2 NH2
R”OH
LiAl(OtBu)3 H
RCHO
RCHO
[-]
A/B
-
-
RCHO$
DIBAL-H
RCH2 OH
RCH2 OH
RCHO
A/B
-
-
RCHO$
Me2 CuLi
RCOMe
-
-
A/B
-
-
-
MeNH2
RCONHMe
RCONHMe,
RCONHMe,
A/B
-
-
-
RCO2 H
R”OH
RCO2 Et,
RCO2 Et,
RCO2 Et^
[-]
-
[RCO2 Et]*
RCO2 H
R”OH^
RCO2 H
RCO2 H,
-
RCO2 H,
-
EtOH
H2 O
RCO2 Et
RCO2 H
R2 NH^
R”OH^
MeCO2 H
(RCO)O(COMe)
(RCO)O(COMe),
RCO2 H,
R2 NH^@
-
(RCO)O(COMe)#
-
A/B
-
RMe2COH,
RMe2COH,
A/B
-
-
[-]
RCO2 H
R”OH
RMe2COH
RMe2COH,
RCOR’
RMe2COH,
RCOMe
RCOMe$
RCO2 H
MeMgBr
MeLi
RMe2COH
RMe2COH
R”OH
R2 NH
*In the presence of acid and after hydrolysis ; #upon heating; $after hydrolysis;
^with acid; @can be stopped at amide stage.
Chapter 21: Amines
The Mannich reaction is of ten
applied for t he preparation of
functionalized amines, both in
the lab and in natur e .
CH3
N
O
OCH3
O
cocaine
O
Chapter 21: Amines
Preparations of amines:
Starting Material
R-X
R= prim. or
sec. alkyl group
Reagent
Intermediate
NH3
R-NH3 X
O
R-X
Reagent in 2. Step
Product
RX; OH
R-NH2
R2NH
R3N
R4N+ X-
H2NNH2
R-NH2
O
NK
N-R
O
O
R-X
NaCN
R-CN
H2, Pd or LAH
R-CH2NH2
R-X
NaN3
R-N3
H2, Pd or LAH
R-NH2
-
Ar-NH2
Ar-NO2
H2/Pd or Fe/HCl
O
R
R'
R
N
H
1. NaH
2. R"-X
R'
R
R'
N
R"
R'
R"
HN
H2, Pd or
NaCNBH3
R'
R
LAH
R'
N
R"
R
O
O
R
R"
O
O
R
N
R"-NH2
NaOBr
NH2
R
N
H
Br
OH-, H2O
R-NH2
Chapter 22: Chemistry of Benzene Substituents
Three distinct mechanisms are generally found in nucleophilic
aromatic substitution reactions:
Elimination-Addition Mechanism: Benzyne is a reactive intermediate in the Dow phenol synthesis
and other substitution reactions of haloarenes with strong bases. The presence of short-lived
benzyne is implied by the scrambling of the isotope labels obs erved in reactions with labeled
compounds. Alternatively, Diels-Alder reactions can be used to trap benzyne intermediates.
Br
NH2
NH2
KNH2
KNH2
+
1 : 1
benzyne
In arenes with strong electron-withdrawing substituents, substitution occurs via an AdditionElimination pathway, and a ne gatively charged, relatively stable intermediate (Meisenheimer
complex) is formed.
-
O
N+
O
X
Nu
Meisenheimer
complex
Chapter 22: Chemistry of Benzene Substituents
A third route for introducing substituents on arenes with electron-donating
substituents is via oxidation to benzoquinones. Subsequent addition of
nucleophiles leads to rearomatization.
OH
O
OH
- 2 e-
Nu
-
Nu
OH
O
OH
Chapter 23: Ester Enolates and Acyl Anion Equivalents
The Claisen co ndensation is the ester analog of the aldol reaction. Under standard conditions
(sodium alkoxide, alkohol), the equilibrium is shifted to the -dicarbonyl compound as a
consequence of the irreversible enolization to the highly resonance-stabilized dicarbonyl enolate.
O
NaOR, HOR
O
+
OR
O
O
R'
O
O
R'
R'
R'=OR, C
O
LDA, -78 °C
OEt
THF
OLi
OEt
O
PhCOCl
Ph
O
OEt
Chapter 23: Ester Enolates and Acyl Anion Equivalents
Especially important are acetoacetate and malonate building blocks (acetoacetic and malonic ester
syntheses):
O
O
O
O
OEt
O
O
OEt
OEt
XCH2CO2R
R-X
R-X
(1 equiv)
RCOX
O
OH
O
O
O
O
R
R
O
R
S
S
Chapter 24: Carbohydrates
N
S
O
OEt
Chapter 24: Carbohydrates
CHO
OH
HOH2C
HO
HO
O
HO
OH
OH
OH
!-D-glucopyranose
OH
CH2OH
HOCH2
HO
H
OH O
HOH2C
H
H
H
HO
OH
HO
HO
O
OH
OH
H
D-glucose in aldehyde form
Emil Fischer (1852-1919)
Chapter 26: Amino Acids, Peptides & Proteins
"-D-glucopyranose
Chapter 26: Amino Acids, Peptides & Proteins