wwu -- chemistry nucleophilic substitution reactions: reactions and synthetic applications

WWU -- ChemistryWWU -- Chemistry

Nucleophilic Substitution Nucleophilic Substitution Reactions:Reactions:

Reactions and Synthetic Reactions and Synthetic ApplicationsApplications


Assignment for Chapter 12Assignment for Chapter 12 Read Sections 12.0 through 12.4Read Sections 12.0 through 12.4 SKIP Pages 1108 (bottom) through 1112 (Sect. 12.4)SKIP Pages 1108 (bottom) through 1112 (Sect. 12.4) New material on N-bromosuccinimide reactionsNew material on N-bromosuccinimide reactions SKIP Sections 12.5 through 12.6SKIP Sections 12.5 through 12.6 Read Sections 12.7 through 12.8Read Sections 12.7 through 12.8 SKIP Section 12.9SKIP Section 12.9 Read Sections 12.10 through 12.11Read Sections 12.10 through 12.11 SKIP Section 12.12SKIP Section 12.12 Read Sections 12.13 through end of chapterRead Sections 12.13 through end of chapter

ORGANIC NOMENCLATURE: Alcohols and EthersORGANIC NOMENCLATURE: Alcohols and Ethers


Problem AssignmentProblem Assignment

In-Text ProblemsIn-Text Problems– 12-1 through 12-812-1 through 12-8

– 12-12 through 12-2412-12 through 12-24

– 12-27 through 12-3212-27 through 12-32

– 12-34 through 12-3912-34 through 12-39

End-of-Chapter ProblemsEnd-of-Chapter Problems– 40 through 4240 through 42

– 46 through 5446 through 54




General Rules for NomenclatureGeneral Rules for Nomenclature

Choose the longest continuous chain of Choose the longest continuous chain of carbon atoms which carbon atoms which includes the carbon atom includes the carbon atom bearing the functional groupbearing the functional group. This chain will . This chain will identify the parent hydrocarbon.identify the parent hydrocarbon.

Number the parent carbon chain from the end Number the parent carbon chain from the end nearest the functional groupnearest the functional group, irrespective of , irrespective of other substitution. other substitution.

Indicate the substituents by name Indicate the substituents by name andand number. number. Assign a number to the carbon atom bearing Assign a number to the carbon atom bearing the functional group.the functional group.

Combine all parts into one word, using correct Combine all parts into one word, using correct punctuation.punctuation.


General Rules for General Rules for Nomenclature (continued)Nomenclature (continued)

Show the presence of the functional group by Show the presence of the functional group by replacing the replacing the -e-e of the alkane ending of the alkane ending (sometimes the (sometimes the -ane-ane) with the appropriate ) with the appropriate ending for the functional group. Show the ending for the functional group. Show the position of the functional group by inserting a position of the functional group by inserting a number into the name immediately number into the name immediately beforebefore the the name of the parent chain.name of the parent chain.


LOCANT PREFIX N STEM SUFFIX

numbers substituents number -ALK(AN)- ending

Block Diagram for Block Diagram for NomenclatureNomenclature


Nucleophilic SubstitutionNucleophilic Substitution

Nu: + X:+ R X Nu R


Nucleophilic SubstitutionNucleophilic Substitution

+ :Nu + :X:..

..

_R X R Nu

substrate nucleophile product leaving group

chloridebromideiodidehydroxidewateralkoxidesalcoholscyanideaminessulfidesacetylidescarbanionscarboxylates

chloridebromideiodidewateralcoholssulfonatesamines


Assisted Nucleophilic Assisted Nucleophilic SubstitutionSubstitution

+ H Br+ _

+R OH R Br H O H


Assisted SAssisted SNN2: Mechanism2: Mechanism1)

2)

R CH2 O + HH R CH2 O H

H

R CH2 O H

H

Br +slow

Br CH2 R + O

H

H


Assisted SAssisted SNN1: Mechanism1: Mechanism

CH3 C C

CH3

O

C CH3

H

CH3 C C

CH3

O

C CH3

H

H

1)

2)

3)

+ H

CH3 C C

CH3

O

C CH3

H

H

CH3 C C

CH3

OC CH3

H

H+

CH3 C C

CH3

C CH3 + Cl CH3 C C

CH3

C CH3

Cl

slow


Alcohol + Hydrogen HalideAlcohol + Hydrogen Halide

This method is best with tertiary alcoholsThis method is best with tertiary alcohols

This reaction works very slowly with primary This reaction works very slowly with primary and secondary alcohols.and secondary alcohols.

Rearrangements are possible!Rearrangements are possible!


Neopentyl Alcohol Neopentyl Alcohol + Lucas Reagent+ Lucas Reagent

CH3 C CH2

CH3

CH3

O H ZnCl2 CH3 C CH2

CH3

CH3

O H

ZnCl2

CH3 C CH2

CH3

CH3

O H

ZnCl2

1)

2)

3)

4)

5)

+

slowCH3 C CH2

CH3

CH3

O H

ZnCl2

+

CH3 C CH2

CH3

CH3

CH3 C CH2

CH3

CH3

CH3 C CH2

CH3

CH3 + Cl CH3 C CH2

CH3

CH3

H + HO ZnCl2 H2O + ZnCl2

Cl


Alcohols + Phosphorus HalidesAlcohols + Phosphorus Halides

3 + PX3

3 +

heatR OH

R X P OH

OH

OH


Alcohol + Phosphorus HalideAlcohol + Phosphorus Halide

This method is best for primary and This method is best for primary and secondary alcohols.secondary alcohols.

This method is generally unsuccessful with This method is generally unsuccessful with tertiary alcoholstertiary alcohols

Rearrangements do not happen with this Rearrangements do not happen with this method.method.


Preparation of TosylatesPreparation of Tosylates

..:R O

H

CH3SCl

O

O

+

CH3S

O

O

OR..

..

N

+ H Cl

???

p-Toluenesulfonyl chloride "Tosyl chloride"

a p-Toluenesulfonate a "Tosylate"

TsCl

R-OTs


Which Alkyl Halide Should I Which Alkyl Halide Should I Use?Use?

If the halide is a better leaving group, the If the halide is a better leaving group, the reaction will go in higher yield.reaction will go in higher yield.

II-- > Br > Br-- > Cl > Cl--

If the halide is cheaper, the reaction will be If the halide is cheaper, the reaction will be more economical.more economical.

ClCl-- > Br > Br-- > I > I--


Which Alkyl Halide Should I Which Alkyl Halide Should I Use? (Part Two)Use? (Part Two)

Best compromise…Best compromise…

Alkyl bromides!Alkyl bromides!

Exception: For CHException: For CH33—X, use—X, use

Methyl iodideMethyl iodide


Addition of Hydrogen Halides Addition of Hydrogen Halides to Double Bondsto Double Bonds

CH CH2RHX

R CH CH3

X

+ R CH2 CH2

X

major minor

This reaction follows Markovnikov’s Rule

Chapter 8, Section 8.4


Free Radical Halogenation of Free Radical Halogenation of AlkanesAlkanes

R CH2 CH3

X2

lightR CH CH3 R CH2 CH2

+

X X major minor

Chapter 3, Section 3.17


Allylic Halogenation with Allylic Halogenation with NN-Bromosuccinimide-Bromosuccinimide

CH CH2CH2R + N

O

O

BrCCl4

heat, light, orperoxides

CH CH2CHR + N

O

O

H

Br

N-Bromosuccinimide (NBS)


Mechanism – Step 1Mechanism – Step 1

N

O

Br

O

free radical

initiatorN

O

O

+ Br



R CH CH CH2

HBr

R CH CH CH2

BrH++

allylic radical

R CH CH CH2 R CH CH CH2

slow


Mechanism – Mechanism – Step 3Step 3

N

O

Br

O

H Br

N

O

Br

O

BrH

N

O

O

H + Br Br

Succinimide

N

O

O

H



R CH CH CH2

+Br Br

R CH CH CH2

+Br

Br


Halogenation at a Benzylic Halogenation at a Benzylic PositionPosition

+ N

O

O

XCCl4

heat, light, orperoxides

+ N

O

O

H

CH2 R

CH R

XX = Br or Cl


Benzylic Substitution – Benzylic Substitution – Mechanism Step 2Mechanism Step 2

Br

BrH+

+

CH R

H

slowCH R

a benzyl radical


Conversion of Alkyl Halides to Conversion of Alkyl Halides to AlcoholsAlcohols

+ H2O +

+ +

R OH

XR OH

H X R X

R X OH

SN1

SN2


Synthesis of EthersSynthesis of Ethers

+ +R X R O R H X R OH


Williamson Ether SynthesisWilliamson Ether Synthesis

+ + 1/2 H2

..

..:

_

+ +..

..

R OH Na(0)

R O Na+

R O R X R O R X

SN2


General Reaction of EpoxidesGeneral Reaction of Epoxides

: :

Nu:

..:..

..

..

Nu C C O

R

R

R

R

Nu C C OH

R

R

R

R

CR

R

C R

R

O

H+


Under Acidic Conditions…Under Acidic Conditions…

:

Nu:

..

..

+

CR

R

C R

R

O

H

Nu C C OH

R

R

R

R


Reactions of EpoxidesReactions of Epoxides

: :_

+(H )

+

HBr +

:OH..

_

..+

(H )+

H +: :

+

CH2CH2

O

CH2CH2

O

CH2CH2

O

CH2CH2

O

C N N C CH2 CH2 OH

Br CH2 CH2 O H

OH CH2 CH2 OH

H

O

H OH CH2 CH2 O H


More Reactions of EpoxidesMore Reactions of Epoxides

NH3

+

+

R:_

+(H )

+

CH2CH2

O

CH2CH2

O

CH2CH2

O

NH2 CH2 CH2 OH

R NH2R NH CH2 CH2 OH

R CH2 CH2 OH


Reactions of Epoxides in Basic Reactions of Epoxides in Basic MediumMedium

CH CH2

O

R + Nu R CH CH2 Nu

OH


Reactions of Epoxides in Acidic Reactions of Epoxides in Acidic Medium Medium

CH CH2

O

R + Nu R CH CH2 OH

H

Nu


Synthesis of Heliannuol ESynthesis of Heliannuol E

CH3

OCH3

O

CHCH2

CHC

CHCH2

CH3

CH3

O

H CH3

OCH3

O

CHCH2

CHCH2

CHC

OH

CH3

CH3

KOH

DMSO

Hydrolyze to remove methyl group.


Synthesis of Heliannuol CSynthesis of Heliannuol C

CH3

OCH3

O

CHCH2

CHC

CHCH2

CH3

CH3

O

H CH3

OCH3 CH

CHCH2

SnCl4

OC

CH

CH2

CH3

CH3

OH

Hydrolyze to remove methyl group.


Synthesis Problem #1Synthesis Problem #1

OH Br


Outline the MechanismOutline the Mechanism

HBrCH3 C CH CH3

CH3

CH3 OH

CH3 C CH CH3

CH3

Br

CH3


HBr or PBrHBr or PBr33??????

CH CH CH2 Br

CH3 C CH CH3

CH3

CH3 OH

CH3 C CH CH3

CH3

CH3 Br

CH CH CH2 OH



CH O

CH3

CH2 CH3CH3 CH2 Br


Synthesis of MTBESynthesis of MTBE(Methyl (Methyl terttert-Butyl Ether)-Butyl Ether)

CH3 C O CH3

CH3

CH3



CH3 CH CH2 CH3 CH CH2 OH

OH


Reactions of EpoxidesReactions of Epoxides

: :_

+(H )

+

HBr +

:OH..

_

..+

(H )+

H +: :

+

CH2CH2

O

CH2CH2

O

CH2CH2

O

CH2CH2

O

C N N C CH2 CH2 OH

Br CH2 CH2 O H

OH CH2 CH2 OH

H

O

H OH CH2 CH2 O H


More Reactions of EpoxidesMore Reactions of Epoxides

NH3

+

+

R:_

+(H )

+

CH2CH2

O

CH2CH2

O

CH2CH2

O

NH2 CH2 CH2 OH

R NH2R NH CH2 CH2 OH

R CH2 CH2 OH


What are the Products?What are the Products?

+

+_

CH3 C NH2

CH3

CH3

CH3 Cl

CH3 CH2 CH2 Br C N



Starting with alcohols, synthesize:

CH3 CH2 CH2 CH2 C C CH2 CH2 CH3


The Synthesis Problem from The Synthesis Problem from Hell!Hell!

CH3 CH2 CH CH CH3

CH3

OH

CH3 CH2 CH CH CH2

CH3


Try this!Try this!

O CH2

CH2OH

???

Plus any additional needed reagents and solvents


..

..

+

Methionine

ATP

+

+_

S-Adenosylmethionine

(S-Adm)

O

H

OH

H

OH

HH

N N

NN

NH2

CH2OPOPOPOH

O

OH

O

OH

O

OH

OH C CH CH2 CH2 S CH3

O NH2

O

H

OH

H

OH

HH

N N

NN

NH2

CH2SCH3

CH2

CH2

CH

COOH

NH2

O P P

O O

OH OH

P OH

O

OH


+

_

Tyrosine

O2

+

_

DOPA

+

- CO2

+

Dopamine

O2

+

Norepinephrine

(Noradrenaline)

(S-Adm)

Epinephrine

(Adrenaline)

OH CH2 C COO

NH3

H

CH3 R

OH CH C H

NH3

H

OH

OH

OH CH2 C H

NH3

H

OH

OH CH C H

NH2

H

OH

OH

CH3

OH CH2 C COO

NH3

H

OH


Change in Assignment Change in Assignment (August 11, 2004)(August 11, 2004)

Include the following sections:Include the following sections:– 12.912.9– 12.1012.10– 12.1112.11– 12.1412.14– 12.1512.15

wwu -- chemistry nucleophilic substitution reactions: reactions and synthetic applications

Documents

nomenclature slide

mechanism slide

chemistry assignment

chemistry general rules

chemistry allylic halogenation

chemistry problem assignment

methyl iodide slide

chemistry block diagram