CHEM 32 - CHAPTER REVIEW
…. not everything you need toknow, but at least a summary ofthe beginning of what you needto know….
Chapter 14: Delocalized !-Systems
R'
R
Z
R
R'
Z
R R
Z Z
R
Z
R
Z
Z
R
Z
R+
! or Lewis Acid
! or Lewis Acid
+
+
! or Lewis Acid
! or Lewis Acid
+
R'
RZ
R
R'
Z
R'
R
Z
R
R'
Z
R'
R
Z
+
! or Lewis Acid
+
! or Lewis Acid
Chapter 14: Delocalized !-Systems
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]
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 Intermediate Product
R R'
O
H2O
R R'
HO OH
hydrate
“ R”OH, H+
R R'
HO OR"
hemiacetal R R'
R"O OR"
acetal/ketal
“ HOCH2CH2OH, H+ “ OO
R R'
“ NaCN, H+
R R'
HO CN
cyanohydrin
“ NaHSO3
R R'
HO SO3Na
bisulfite adduct
“ H2NR”
R R'
HO NHR"
R R'
NR"
imine
“ HNR*R”
R R'
HO NR*R"
R R'
NR*R"
enamine
“ HONH2
R R'
HO NHOH
R R'
NOH
oxime
“ H2NNHR”
R R'
HO NH-NHR"
R R'
N-NHR"
hydrazone
“
Ph3P CR*R"
O PPh3
RR' R"
R*
oxaphosphetane R R'
R" R*
alkene
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
O
R'
H
R2C C
O
R'
H
! carbon atom of enol is nucleophilic; it attacks
electrophilic reagents
carbonyl group is electro-philic; nucleophilic reagents add to carbonyl group
! proton is relatively
acidic (pKa!20); it can be removed by bases
-Halogenation. Halogens react with
aldehydes and ketones by substitu-
tion; An acid catalyst (or base) in-
creases the rate of enolization
(enolate formation), which is the rate-
O OH O
Br
O
Br Br
CH3CO2H, Br2
determining 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 OBr
O
Br
O
BrBr
HO
OBr
BrBr
H+
NaOH, H2O, Br2
Chapter 18: Enols & Enones
RCH2 R'
OHO
RR'
NaOCH2CH3
RCH2 R'
O
R
R'NaOCH2CH3
RCH2 C
O
R'
(2 equiv)
HOCH2CH3
-H2O
HOCH2CH3
O OLi
H2O
CH3CH2CHO
CH2CH3
O OH
CH2CH3
O OLi
85%(workup)
THF, -78° C
LDA
O O
O
(MVK)
46%
+
NaOCH2CH3,
CH3CH2OH
Chapter 19: Carboxylic Acids
R Cl
O
R O
O O
R R OR'
O
R OH
O
R NH2
O
R O-
O
reactivity
>>>>>
RO OR
O
R2N NR2
O
R2N OR'
O
RO Cl
O
carbamate/urethaneureacarbonatechloroformate
Chapter 19: Carboxylic Acids
Reagents for the interconversion of carboxylic acid derivatives:
R Cl
O
R O
O O
R R OR'
O
R OH
O
R NR2
O
R O
O
R-C!N
R Cl
O
- R O
O
R'OH, py H2O R2NH, py H2O, OH-
-
R O
O O
R - - R'OH, py H2O R2NH, py H2O, OH-
-
R OR"
O
- - R'OH, H+/B-
H2O, H3O+ R2NH H2O, OH-
-
R OH
O
SOCl2 , -H2O R'OH, H+, - DCC, R2NH OH-
-
R NR2
O
- - - H2O, H3O+
- OH-, SOCl2
R O
O
- R Cl
O
- H3O+
- - -
R-C!N
- - R'OH, H+,H2O
H2O, H+
H2O, H+
OH-,
-
Chapter 20: Carboxylic Acids & Mass Spectroscopy
The Hofmann rearrangement involves:
R N
O
nitrenes;
R-N=C=O, isocyanates, and
R
HN OH
Ocarbamic acids
Chapter20:Carboxylic
Acids &
Mass
Spectroscopy
Chemistry of carboxylic acid derivatives:
R Cl
O
R O
O O
R R OR"
O
R OH
O
R NR2
O
R O
O
R-C!N
LAH RCH2OH RCH2OH RCH2OH,
R”OH
RCH2OH RCH2NR2 RCH2OH RCH2NH2
LiAl(Ot-Bu)3H
RCHO RCHO [-] A/B - - RCHO$
DIBAL-H RCH2OH RCH2OH RCHO A/B - - RCHO$
Me2CuLi RCOMe - - A/B - - -
MeNH2 RCONHMe RCONHMe,
RCO2H
RCONHMe,
R”OH
A/B - - -
EtOH RCO2Et RCO2Et,
RCO2H
RCO2Et,
R”OH^
RCO2Et^ [-] - [RCO2Et]*
H2O RCO2H RCO2H RCO2H,
R”OH^
- RCO2H,
R2NH^
- RCO2H,
R2NH^@
MeCO2H (RCO)O-(COMe)
(RCO)O-(COMe),
RCO2H
- (RCO)O-
(COMe)# - A/B -
MeMgBr
RMe2COH RMe2COH,
RCO2H
RMe2COH,
R”OH
A/B - - [-]
MeLi RMe2COH RMe2COH RMe2COH,
R”OH
RCOR’ RMe2COH,
R2NH
RCOMe RCOMe$
*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 nature.
NCH3 O
OCH3
O
Ococaine
Chapter 21: AminesPreparations of amines:
Starting Material Reagent Intermediate Reagent in 2. Step Product
R-X NH3 R-NH3 X R-NH2
R2NH
R3N
R4N+ X-
R-XNK
O
O
N-R
O
O
H2NNH2 R-NH2
R-X NaCN R-CN R-CH2NH2
R-X NaN3 R-N3 R-NH2
Ar-NO2 H2/Pd or Fe/HCl Ar-NH2
R R'
O
R R'
NR"
R R'
HNR"
R NH
O
R'
R
NR"R'
R N
O
R'
R"
R NH2
ONaOBr OH-, H2O
R NH
O
Br R-NH2
RX; OH
R= prim. or sec. alkyl group
H2, Pd or LAH
H2, Pd or LAH
-
R"-NH2 H2, Pd or NaCNBH3
1. NaH2. R"-X LAH
Chapter 22: Chemistry of Benzene Substituents
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
KNH2
benzyne
KNH2
NH2
+
NH2
1 : 1
In arenes with strong electron-withdrawing substituents, substitution occurs via an Addition-
Elimination pathway, and a ne gatively charged, relatively stable intermediate (Meisenheimer
complex) is formed.
X
NuN+
-O
-OMeisenheimer complex
Three distinct mechanisms are generally found in nucleophilic
aromatic substitution reactions:
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
OH
- 2 e-
O
O
Nu-
OH
OH
Nu
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.
OR
O
R'
O
R'
O O
R'
O ONaOR, HOR
R'=OR, C
+
OEt
O
THFOEt
OLi
Ph OEt
O OPhCOClLDA, -78 °C
Chapter 23: Ester Enolates and Acyl Anion Equivalents
Especially important are acetoacetate and malonate building blocks (acetoacetic and malonic ester
syntheses):
OEt
O O
R-X
OEt
O O
OEt
O O
R
R-X
R
O
OEt
O O
XCH2CO2R
RCOX
R
O O
O
O
OH
(1 equiv)
N
SS S
Chapter 24: Carbohydrates
Chapter 24: Carbohydrates
O
HOH2C
HOHO
OH
OH
O
HOH2C
HOHO
OH
OH
HO
OH
OH
CHO
OH
CH2OH
O
H
H
OH
HO
H
H
HO
HOCH2
H
OH
!-D-glucopyranose "-D-glucopyranoseD-glucose in aldehyde form
Emil Fischer (1852-1919)
Chapter 26: Amino Acids, Peptides & Proteins