70545143 organic II reactions BETA

Facilitator: Chris Lovero

Organic Chemistry II Reactions

Task

Reaction

Symmetrical
ethers through
dehydration of 1o
alcohols

R OH

H2SO4

x2

140oC

O CH3

Cleavage of ethers
byvstrong acids

Notes

R

*cannot be unsymetrical

O R

(you will get mixtures!)

Br

HBr

*can also use HI, HCl,

+

H3C

Br

etc
* vinyl or aryl do not get
cleaved (NO SN2 ON
SP2)

HBr

Br

O

HO
*basically forms

Autoxidation

R
R O

R

O2 (xs)

H

R O

slow

R

+

R O O

MCPBA

CH3

Intramolecular
Williamson

Br

H

EXPLODE!

CH3

*epoxide will form along

O

the more substituted

CH3

alkene

*SN2 like

O

NaOH

OH

peroxides.... which

R

R

CH3

MCPBA

O OH

R

*forms O- that attacks
halogenated C

OH
NaOH

H3C

H3C

O

Cl
Opening of
Epoxides

CH3

CH3
H3O+

O
D

H2O

CH3

D

OH

2)H3O+

*weak Nu are good
*more substituted side
attacked

D
OH

1)-OH

O

OH

*activate the O first

*SN2 like (least subs)
so strong Nu and base

CH3
D
OH

*Grignard reagent and
acetylide anion can
work tooo

1


Facilitator: Chris Lovero

Organic Chemistry II Reactions

Task

Reaction

Free Radical
Halogenation
Expanded

Notes
*Low T: more stable TS

CH3

NBS

hv 0oC

CH3

CH3

*High T: more stable

Br

compound

CH3

NBS
60oC

transition state
CH3

.

CH3

.

CH3

CH3

CH3
CH3

Br
Conjugated
Systems

*Low T: more stable TS

*in this example we will examine the
case of HBr

*High T: more stable
compound

CH2

H2C

*NOTE: If more than one

H3O+

HBr

conjugated system

Br2

possibly exists, examine

the transition states of

HBr / 40oC

HBr / 0oC

H

each one and do the
reactions with the more

H

stable transtion states!

H2C
Br

Br

transition state
+

Diels-Alder
Reaction

D = donating group

+
*1,2 or 1,4 adduct

W = withdraw group

D

heat

+

*know endo rule

D

*Diene and Dienophile
*Know Stereochem

W

W
D

D
heat

+
W

W

*PRACTICE THIS!!!

2


Facilitator: Chris Lovero

Organic Chemistry II Reactions

NOTE: FROM HERE, YOU HAVE TO KNOW YOUR META, ORTHO, AND PARA DIRECTORS
Task

Reaction

Halogenation of
Benzene

Notes
*X = Cl or Br

X

X2, FeX3 or
(I2 / CuCl2)

Nitration of
Benzene

NO2

HNO3

*H2SO4 acts as a
catalyst

H2SO4 heat

Sulfonation
(fuming sulfuric)

SO 3H

SO3 / H2SO4

*REVERSIBLE DUE TO
ENTROPY

heat

SO 3H

+

H2SO 4

+

H2O

*watch rearrangement!

Friedel-Crafts
Alkylation

R

RCl

*no strong deactivators
(no strong W grps)
*no amino groups

AlCl3

*watch for polyalkylation

Friedel-Crafts
Acetylation

O

O

*no strong deactivators
(no strong W grps)

Cl

R

R

*no amino groups

AlCl3

O

Gatterman-Koch
Formation
(forming
benzaldehyde)

Clemmensen
Reduction

CO / HCl

*no strong deactivators
(no strong W grps)

H

*no amino groups

AlCl3 / CuCl

*avoid using this

O
Zn(Hg)

R

HCl

reactant in the presence

R

of alkenes, alkynes,
alcohols and amines.

3


Facilitator: Chris Lovero

Organic Chemistry II Reactions

Task

Reaction

*Do not confuse with

Reduction of Nitro
group into Amino
Group

Zn, Sn, or Fe

W = withdraw group

X = leaving grp (halide)

NH2
*need Strong W groups

Nu = nucleophile

X

ortho and/or para to

Nu

Nu (2eq)

W

W

Clemmenson Red.

HCl

NO2

Nucleophilic
Aromatic

Substitution of Aryl
Halides:

Notes

leaving group.

W

W

heat, pressure

*Nu can be OH-, RO-,

Addition /
Elimination

NH3.

W

*NOTE: If - OCH3 is the

W

Nu, only need 1 eq

X

Nucleophilic
Aromatic
Substitution of Aryl
Halides:
Elimination /
Addition

OH

*occurs when Strong W
group is not O/P

1) NaOH (2eq) / 340oC / 2500 psi

*formation of benzyne

2) H3O+

in mechanism

X

* Nu can be OH-, RO-,

NH2
NaNH2 /

NH2

+

NH3 (l)

NH2.

*will get a mixture (like
second example)

CH3

CH3

CH3

Chlorination of
Benzene

*8 different stereochems

Cl

actually occur

Cl

Cl

3 Cl2 / heat
pressure

*this particular molecule
is the commercial

Cl

Cl

compound Rid
(lice killer)

Cl
Catalytic
Hydrogenation

-

3 H2 / 1000 psi / 100oC
Ru or Rh (Pt,Pd,Ni also)

Birch Reduction

W

W

*withdraw groups ->
sp3

0

D

Na or Li

0

NH3(l) / ROH

*donating groups ->

D

sp2

4


Facilitator: Chris Lovero

Organic Chemistry II Reactions

Task

Reaction

Side Chain Rxn:
Oxidation

Notes
*Can use either reagent

CO2H

(CH2)n

*Does not work for bulky

KMnO4/H2O
O

groups.

OH-/100oC

HO2 C

CO2 H
CO2 H

Na2Cr2O7 / H2SO4

(no rxn)

heat

Halogenation of
side chains

*If aromatic ring is

Cl
CH2CH3

Cl2 / light

activated, use NBS

+
Cl

54%

44%

Br2 (or NBS) / light

instead of Br2
*Pay attention to Temp
(if it's low or high)
*WILL EXPLAIN THIS

Br

BETTER IN CLASS

Nucleophilic Subs
of Benzylic
Halides

major!

*SN1

CH2 Br

CH3OH

*SN1 or SN2 or E2?

+

Depends on conditions!

heat

*Resonance form that

+

does not disrupt the

CH2 OCH3

aromaticity is more
stable

I

NaI

*SN2

Br

acetone
CH3CH2O-

*E2

Na+

Rxns of phenols
similar to alochols

O

NaOH

-

*2nd rxn is Fischer
Estherification
*3rd rxn is only one that

OH

RCO2H

O
O

or RCOCl
PBr3

R

OH

(no rxn)

is different!

5


Facilitator: Chris Lovero

Organic Chemistry II Reactions

Task

Reaction

Oxidation of
Phenols to
Quinones

HO

Notes

*This reaction forms a

Na2Cr2O7

OH

O

H2SO4

Formation of
Salycilic Acid

*Phenoxide anion can

1) NaOH

OH

OH

O

2) CO2
3) H3O

REVIEW:
Oxidation of
alcohols

D-A dienophile!

O

2o alcohols

react with the weak

OH

electrophile because it

+

is so strongly activated.

*any [ox] can be used

Na2CrO7

*KMnO4 and NO3 can

H2SO4 / H2O

OH

be used but they are
harsh.

O

CrO3 / H2SO4 / H2O
acetone / 0oC
(Jones reagent)

PCC
CH2Cl2

H

1o alcohols

PCC

OH

*Only use PCC because
Jones reagent will

O

yield carboxyllic acid

CH2Cl2

REVIEW:
Cleavage of
Alkenes by
Ozonolysis

H3C

CH3

H

O

R

H2O / H2SO4

R

H

R

+

CH3
O

H

2) (CH3)2S

CH3

REVIEW:

Hydration of
Alkynes

H3C

1) O3

H

CH3

*Really know the

R
CH3

HgSO4

HO

1) Sia2BH

R

2) H2O2 / OH-

H

H

mechanism now
and how the enols

O

tautomerize.

R

1

H

H
RCH2

either
reagent

O

OH

mixture of ketones

6


Facilitator: Chris Lovero

Organic Chemistry II Reactions

Task
Dithiane Synthesis
of Aldehydes and
Ketones

Reaction

Notes
*Dithiane will be given

O
1) BuLi

S
H

S

S

2) R - X

H

R

S

R

HgCl2

H

*BuLi =

H3O+

H

CH3(CH2)2CH2-Li
*Halide must be methyl
or 1o

1) BuLi
2) R1 - X

S
R
Ketones from
Carboxylic Acids

O
R

Ketones from
Nitriles

S
R

1

O

H3O+

R

HgCl2

2) H3O

Aldehydes from
Acid Chlorides

*2 eq because first
is used to make salt

+

R

R

1

O

1) R1-MgX

R C N

1

O

1) R1 - Li (2eq)

OH

R

R

2) H3O+

R

1

*lithium aluminum tri(t-butoxy)hydride

LiAlH(OtBu)3

O
R

O

*Rosenmund Reduction

Cl

R

H2 / Pd / BaSO4 / S

H

*Make sure you know

Ketones from
Acid Chlorides

O
R

O

(R1)2CuLi

R

Cl

how to form Gilman

R

Reagent (refer to Corey-

1

House in previous rxn
sheet)

Wittig Reaction:
Ald and Ketones
ONLY

H

*Know how to prep the

H

phosphorous ylide!

H

O

(Ph)3

*trans is more stable

P C

because you want

+

H

bulky groups to be
furthest away from
each other.

H
H

maj

7


Facilitator: Chris Lovero

Organic Chemistry II Reactions

Task
Aldehydes and
Ketones:
Formation of
Cyanohydrins

Reaction

O
R

*Aldehydes or

OH

-

unhindered ketones

CN

H

R C CN

HCN

*will use this as a

H

reagent in the future.

OH

O
H3CH2C

Notes

NaCN

H3CH2C C CN

H+

H

H
*non AQ favors reactant

Aldehydes and
Ketones: Addition
of 1o Amines

O

RNH2

C

Wolf-Kishner
Reaction

*AQ favors product

C N R

H+

*avoid halogens and

O

NH2NH2

other good LGs.

KOH/DMSO

(Use Clemmensen
instead)

Aldehydes and
Ketones: Addition
of 2o Amines

O

(H3C)2N

(CH3)2NH
H3O+

Acetal Formations
"protected
carbonyls"

CH3

OEt
CH3

2(CH3CH2OH)
H+

O

EtO

*aldehyde protected
*easier to just use

OH OH

O

1) OH

+

HO

before ketone because

CH 3

OH /H

it is more reactive

2) CH3MgBr

H

H

3) H3O+

O

O

O

O

-

CH 3

H
O

O

H
O

O

8