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



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



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



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



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



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



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



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

Organic II Reactions BETA

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