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

*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

HO
*basically forms

Autoxidation

R
R O

O2 (xs)

R O

slow

R O O

MCPBA

CH3

Intramolecular
Williamson

Br

EXPLODE!

CH3

*epoxide will form along

the more substituted

CH3

alkene

*SN2 like

NaOH

OH

peroxides.... which

CH3

MCPBA

O OH

*forms O- that attacks

halogenated C

OH
NaOH

H3C

H3C

Cl
Opening of
Epoxides

CH3

CH3
H3O+

O
D

H2O

CH3

OH
OH

OH

2)H3O+

*weak Nu are good

*more substituted side
attacked

1) 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

Facilitator: Chris Lovero

Organic Chemistry II Reactions

Task

Reaction

Free Radical
Halogenation
Expanded

Notes
*Low T: more stable TS

CH3

NBS
o

hv 0 C

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

each one and do the

reactions with the more

stable transtion states!

H2C
Br

Br

transition state
+

Diels-Alder
Reaction

D = donating group

+
*1,2 or 1,4 adduct

W = withdraw group

heat

*know endo rule

*Diene and Dienophile

*Know Stereochem

W
D

D
heat

+
W

*PRACTICE THIS!!!

Facilitator: Chris Lovero

Organic Chemistry II Reactions

NOTE: FROM HERE, YOU HAVE TO KNOW YOUR META, ORTHO, AND PARA DIRECTORS
Task
Reaction
Notes
Halogenation of
Benzene

*X = Cl or Br

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

RCl

*no strong deactivators

(no strong W grps)
*no amino groups

AlCl3

*watch for polyalkylation

Friedel-Crafts
Acetylation

*no strong deactivators

(no strong W grps)

Cl

*no amino groups

AlCl3

Gatterman-Koch
Formation
(forming
benzaldehyde)

Clemmensen
Reduction

CO / HCl

*no strong deactivators

(no strong W grps)

*no amino groups

AlCl3 / CuCl

*avoid using this

O
Zn(Hg)

HCl

reactant in the presence

of alkenes, alkynes,
alcohols and amines.

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

ortho and/or para to

Nu

Nu (2eq)

Clemmenson Red.

HCl

NO2

Nucleophilic
Aromatic
Substitution of Aryl
Halides:

Notes

leaving group.

heat, pressure

*Nu can be OH-, RO-,

Addition /
Elimination

NH3.

*NOTE: If - OCH3 is the

Nu, only need 1 eq

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

* 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

*withdraw groups ->

sp3

Na or Li

NH3(l) / ROH

*donating groups ->

sp2

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

NaI

*SN2

Br

acetone
CH3CH2O-

*E2

Na+

Rxns of phenols
similar to alochols

NaOH

*2nd rxn is Fischer

Estherification
*3rd rxn is only one that

OH

RCO2H

O
O

or RCOCl
PBr3

OH

(no rxn)

is different!

Facilitator: Chris Lovero

Organic Chemistry II Reactions

Task

Reaction

Oxidation of
Phenols to
Quinones

HO

Notes
*This reaction forms a

Na2Cr2O7

OH

D-A dienophile!

H2SO4

Formation of
Salycilic Acid

*Phenoxide anion can

1) NaOH

OH

OH

2) CO2

react with the weak

OH

electrophile because it

3) H3O+

REVIEW:
Oxidation of
alcohols

2o alcohols

is so strongly activated.

*any [ox] can be used

Na2CrO7

*KMnO4 and NO3 can

H2SO4 / H2O

OH

be used but they are

harsh.

CrO3 / H2SO4 / H2O

acetone / 0oC
(Jones reagent)

PCC
CH2Cl2

1o alcohols

PCC

OH

*Only use PCC because

Jones reagent will

yield carboxyllic acid

CH2Cl2

REVIEW:
Cleavage of
Alkenes by
Ozonolysis

H3C

CH3

H2O / H2SO4

CH3
O

2) (CH3)2S

CH3

REVIEW:
Hydration of
Alkynes

H3C

1) O3

CH3

*Really know the

R
CH3

HgSO4

HO

1) Sia2BH

2) H2O2 / OH-

mechanism now
and how the enols

tautomerize.

H
RCH2

either
reagent

OH

mixture of ketones

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

2) R - X

HgCl2

*BuLi =

H3O+

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

H3O+

HgCl2

2) H3O

Aldehydes from
Acid Chlorides

*2 eq because first
is used to make salt

1) R1-MgX

R C N

1) R1 - Li (2eq)

OH

2) H3O+

*lithium aluminum tri(t-butoxy)hydride

LiAlH(OtBu)3

O
R

*Rosenmund Reduction

Cl

H2 / Pd / BaSO4 / S

*Make sure you know

Ketones from
Acid Chlorides

O
R

(R1)2CuLi

Cl

how to form Gilman

Reagent (refer to Corey-

House in previous rxn

sheet)

Wittig Reaction:
Ald and Ketones
ONLY

*Know how to prep the

phosphorous ylide!

(Ph)3

*trans is more stable

P C

because you want

bulky groups to be
furthest away from
each other.

H
H

maj

Facilitator: Chris Lovero

Organic Chemistry II Reactions

Task
Aldehydes and
Ketones:
Formation of
Cyanohydrins

Reaction
O
R

*Aldehydes or

OH

unhindered ketones

CN

R C CN

HCN

*will use this as a

reagent in the future.

OH

O
H3CH2C

Notes

NaCN

H3CH2C C CN

H+

H
*non AQ favors reactant

Aldehydes and
Ketones: Addition
of 1o Amines

RNH2

Wolf-Kishner
Reaction

*AQ favors product

C N R

H+

*avoid halogens and

NH2NH2

other good LGs.

KOH/DMSO

(Use Clemmensen
instead)

Aldehydes and
Ketones: Addition
of 2o Amines

(H3C)2N

(CH3)2NH
H3O+

Acetal Formations
"protected
carbonyls"

CH3

OEt
CH3

2(CH3CH2OH)
H+

EtO

*aldehyde protected
*easier to just use

OH OH

1) OH

HO

before ketone because

CH 3

OH /H

it is more reactive

2) CH3MgBr

3) H3O+

CH 3

H
O

H
O

Ray
Reactions

Tasks
1. Carboxylic
acids to acyl
chlorides

2. Alcohols to
alkyl halides

Notes

SOCL2

1.

OH

CL
SOCL2

R-OH

2.

O
OH

Addition of
Hydrides

R-CL

(COCL)2
CL

O-

1. LiAlH4

Catalytic
Hydrogenation

O
H2, Raney Ni

OH

Additions of 1
Amines (Imines)

*non Aqueous favors

imine

R'NH2

Imine Product
Derivatives

OH

2. H3O+

H+

*Aqueous favors
ketone and amine

R'

Ph-HN
N

N
NH2NHPh/H+

OH

NH2OH/H+

O
NH2NH2/H+

NH2NH-C-NH2/H+

O
N

H
N

NH2

NH2

Additions of 2
Amines
(Enamines)

*follows ZAITSEV'S
RULE

(R)2NH
H3O+

(R)2N

Ray
Reactions

Tasks

Notes

Oxidation of
Aldehydes to
Carboxylic Acids:
Silver Reagents

*KMnO4
or
*CrO3/H2SO4/H2O/acteone
or
*Na2Cr2O7/H2SO4/H2O

O
Ag2O/THF/H2O

OH

OR
O

1. Ag(NH3)2+ OH- (Tollen's Reagent)

CH2OH

CH2OH

2. H+

OH

O
Carboxylation of
Grignard
Reagents

X= halide

O
X

1. Mg / ether
2. CO2 / ether
3. H3O+

OH

2 and 3
MgX

Hydrolysis of
Nitriles

CN

CN

Ester Formation
from Acid
Chlorides

H3O+
heat

OH
O

OHheat

O-

R' OH
R

CL

Amide Formation
from Acid
Chlorides

O
CL

NH3
O

CL

R' NH2

N
H

R'

O
CL

O
R

*1

NH2

Synthesis of
Esters: Fischer
Esterification

R'

R2' NH2

OH

!3

NR2'

1. R'-OH
2. H+

O
R

!2

R'

Ray
Reactions

Tasks
Esterification
with
Diazomethane

Direct Amide
Synthesis

O
OH

*SN2

*Great Yield

CH2N2

OH

Reduction of
Carboxylic Acids

Notes

OCH3

R' NH2

NHR'

OH

H3C
NC

OH
NH2

1. LiAlH4/Et2O
2. H3O+

OR"

1. LiAlH4/Et2O
2. H3O+

H3C

OH

H2NH2C

CH2NH2

*reacts with aldehydes,

ketones, esters, carboxylic
acids, and epoxides (with
H3O+ or H2O)
*BUT nitriles, amides, and
N3 produce R-NH2 (with
H2O)

R'
Diborane
Reduction

R'CH2OH +

NC

*VERY SELECTIVE!

O
1. B2H6 / diglyme
2. H3O+

OH
NH2

H3C

R"OH

H3C

OH
NH2

NC

O
Decarboxylation:
Hunsdiecker
Reaction

1. HgO or Ag2O or Pb(OAC)4

2. heat / Br2 / CCl4

OH

R
Carboxylic Acid
from Acid
Chlorides

O
R

R Br

lose

OH

H2O
Cl

OH

Anhydrides from
Acid Chlorides

O
R

*Carboxylics reacts
faster with B2H6 than
any other functional
group

R'
Cl

OR

O
O

R'

*converts Carboxylic
acids into alkyl
halides with 1 less
carbon

Ray
Reactions

Tasks

Notes

Cyclic Anhydrides

*5,6 member rings are

best

O
O
OH

HO

O
O
Alpha
Halogenation of
Ketone

*X= Cl2 / I2 / Br2

* NO FREAKING
ALDEHYDES

X2 / CH3COOH

*Most SUB
ALKENE:MAJOR
*Least SUB
ALKENE:MINOR

Alpha
Bromination of
Carboxylic Acid:
Hell Volhard
Zelinksy

Aniline with
Nitrous Acid
(HNO2)

1. PBr3 / Br2
2. H2O

OH

*carboxylics do not
enolize under acidic
or basic conditions

O
OH
Br

1. HNO3 / H2SO4

2. Zn, Fe, or Sn / HCl

NH2

NO2

Act.

Cl or Br
3. NaNO2 / HCl

Act.
CuCl
or
CuBr

OH
H3O+/!

KI
1. HBF4
2. !

NCL

CuCN

CN
H3PO2

Ray
Reactions

Tasks
Cyclic Anhydrides

Notes

O
OCH3

CH3OH

OH

O
Synthesis and
Reactions of
Anhydrides

O
R

NaOH

OH

+
R

OH

O
O

OH

OR'

AlCl3

R
O

R' OH

*Friedel Crafts
acylation: NO
DEACTIVATING OR
AMINO GROUPS

O
2x

R
O

O
R

H2O

O
O

O-

O
R Cl

NH3 or R'NH2 or R'2NH

+
NH3

OH

OH

Synthesis and
Reactions of
Esters
R

Cl
R'OH

R"
R"

OH
1. R"MgX or R"Li
2. H3O+

R'OH / H+

+ R'OH

OH

or

+ R'O-

O-

R"OH / H+
xs

O
OR''

O
R"MgX or R"Li

H2O
H+ or OH-

O
R

OR'
1. DIBAH
2. H3O+

R"

1. LiAlH4
2. H3O+

RCH2OH + R'OH

NH3 or
R''NH2 or
R''2NH

NH2

Cyclic Esters

*5,6 membered ring

O
O
HO

H+
OH

Ray
Reactions

Tasks
Cyclic Anhydrides

Notes

O
OH
OH

1.

!
>100C

O
O

2x CH3CO2H

2.

~800C

O
O

3.

O
O

OCH3

CH3OH

OH

Synthesis and
Reactions of
Amides

*rxn 1 reacts ONLY

WITH AMIDES

R
3
2
1

NR2

NR2

NHR

NH2

(1)
1. LiAlH4
2. H2O or H3O+

*rxn 2 nucleophilic
acyl substitution and
get AMINE PRODUCT

NHR
(4)
POCl3 or SOCl2 or P2O5

(3)
Br2 / NaOH / H2O

BASE PRODUCT:

ACID PRODUCT:

NH4

OR

*rxn 3 get AMINE

PRODUCT

*rxn 4 reacts ALL 1"

AMIDES and get
NITRILE PRODUCT

NH2

O-

OH

R C N

NH2

(2)
H2O / Heat
H+ or OH-

1. maleic anhydride

Synthesis and
Reactions of
Nitriles

1. LiAlH4
2. H2O or H3O+

or

LiAlH4

R CH2NH2

H2 / Pt or Ni

R CH2NH2

H2O / Heat
H+ or -OH
BASE PRODUCT:

ACID PRODUCT:

NH4

Haloform
Reaction

O
R

CH3

OH

OR

X2 (xs)
NaOH (xs)

O-

NH3

*REACTS ONLY
WITH METHYL
KETONES

O
R

O-

HCX3

Ray
Reactions

Tasks
Alkylation of
Ketones, Esters,
and Nitriles: LDA

O
H3C

1. LDA
2. CH3CH2Br

CH3

(lithium diisopropyl
amide)

Notes

1.

OH2C C

H3CH2CH2C

CH3

2.

CH3CH2CN

1. LDA
2. CH3Br

1. LDA
2. CH3Br

CN
H3C

O
Ha

CH3
Hb

1. LDA
2. CH3Br

CH3

Ha
MAJOR
(less bulky)

+
O
CH3

Hb
Minor
(more bulky)

1. LDA
2. CH3Br

CN
O

Hydrolysis of
Nitriles
(extended)

R CN

R CN

CH3

CHO

OHH2O

CN
O

NH2
O

H+ (non-aqueous)

OHH2O

CHO

H+ (non-aqueous)

NH2

O-

OH

*Basic conditions:
Carboxolate Anion
watch out for
dimerization.

*Acidic conditions:
must be non-aqueous.
nitrile group unaffected
if H3O+ is utilized.

Ray
Reactions

Tasks
Electrophilic
Aromatic
Substitution of
Aniline

Notes
NH2

NH2
Br

Br2 / H2O

1.

2. NO AMINO NOR
DEACTIVATING

Br

3. EXPLODE !

Br
NH2

O
Cl

2.

NO F.C.

AlCl3
NH2

HNO3 / H2SO4

3.
Add Groups to
Anilines

NH2

NH

Cl

BOOM!

NH
Cl

AlCl3

-OH

/!

O
NH2

Br2 / FeBr3

O
NH
-OH

/!

Br
Hofmann
Elimination

NH2

Br

(MAJOR)

1. CH3I (xs)
2. Ag2O / H2O / !

NH2

* Has to make 3
AMINE and serves as
a LG!
*Least

(minor)

sub
alkene is MAJOR
*Most sub Alkene is
minor

Formation and
Reduction of
Azides

Br
1.

1. NaN3
2. LiAlH4
3. H2O

NH2

N3

2/3

*Forms 1 amines only

Ray
Reactions

Tasks
Hofmann
Rearrangement

Notes

O
X2 / H2O / NaOH
R

NH2

X2 / H2O / NaOH
NH2

R NH2

NH2

O
NH2
lose

Curtius
Rearrangement

O
Cl

1. NaN3
2. H2O / !

NH2

GOOD LUCK ON CH. 22 REACTIONS!

Ti To: Who is Olivia? V.1.0

Alpha
Substitution
Ketone
Halogenation

Acid: any organic acid

i.e acetic acid
Base: any base such
as NaOH or LDA
*Basic condition
cannot form monohalogenated
products.
Intermediate is an
enol, so Zaitsevs rule
applies. More
substituted alkene
will form major
product unless using
Hoffman bases.

Carboxylic
acids
(HellVolhardZelinsky)
1.

Overview:
1. Converts the
acid to an
acid halide
Halogenate through
enol reactions

*In base, no mono substitution. Will saturate. Under acidic condition, the
acid halides hydrolyze to carboxylic acid.

Ti To: Who is Olivia? V.1.0

Alkylation
(Ketone,
Ester, and
Nitriles)

1.Occurs in acid/basic
conditions. In basic
condition, the base
must be strong and
bulky in order to
ensure 100% enol
formation. *Use LDA*
Basic conditions are
more favorable
because enolate
yields are better than
in acidic conditions
2. Alkylation does not
react with aldehydes
in this manner. Refer
to Stork synthesis,
and aldol
condensation.
3. LDA is bulky, attack
least hinder proton.
4.Must have alpha
hydrogen.

Stork
Synthesis

NH
N

acid/base

CH3CH2Br

H2O/H3O+

1. Form
enamine from
ketone, and
aldehydes.
2. Enamine can
attack
R-X (SN2)
Acid halides
3. Hydrolysis

Ti To: Who is Olivia? V.1.0

Alkylation of
beta
dicarbonyls

Can use any base

because alpha proton
is acidic enough due
to di-carbonyls.
Therefore, enol form
predominates.

Condensation
Reactions
Decarboxylation

Aldol
Condensation

Must have at least

one carboxylic acid
group. Only occurs in
acidic condition.
Adding acid to ester
and acid halides will
convert them to
carboxylic acid.
1. Forms betahydroxy
ketones/aldehyde
s
2. Do not want 100%
enolate. Do not
use LDA. Use
weak organic
bases.
3. Mixed Aldols can
be made when
two different
aldehydes are
used because enol
can form from
either.
4. Restriction: Must
have alpha proton
to form enolate
for the
condensation.

Ti To: Who is Olivia? V.1.0

O

Intramolecular
aldol
condensation.

NaOEt/EtOH/Heat

Ha

Hb

HO

Formation of enolate
due at Ha. Forming enolate
at Hb do not form ring
because of ring strain.
Protonation
o-

1.

Readily forms 5
or 6 member
rings. Smaller
rings have
steric
hinderance.
Larger rings are
not like to form
because groups
are farther
away.
2. Requires heat
because we
want an
intramolecular
reaction
instead of
intermolecular
reaction.