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

Chapter 26: Amino Acids, Peptides & Proteins