ucleophilic a substitution 9...2019/08/08  · chapter 21, carboxylic acid derivatives l9-1 chem 8b,...

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Chapter 21, Carboxylic Acid Derivatives L9-1 CHEM 8B, Lecture 9 Carboxylic Acid Derivatives: Acid Chlorides, Anhydrides, Esters, & Amides - Nomenclature - Nucleophilic Acyl Substitution (NAS) - Addition of Grignards – another combo mechanism (NAS + Nuc Add’n) NUCLEOPHILIC ACYL SUBSTITUTION (NAS) REACTIVITY SERIES (TOWARD NAS) 9 2 I not always 0 LG Hd itonl.ooqfcwfatgi.dk it i ii ROH OR poor LG ROH LG NR not LG HNRz a HNREOKLGR corltkasteact.ve

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Page 1: UCLEOPHILIC A SUBSTITUTION 9...2019/08/08  · Chapter 21, Carboxylic Acid Derivatives L9-1 CHEM 8B, Lecture 9 Carboxylic Acid Derivatives: Acid Chlorides, Anhydrides, Esters, & Amides

Chapter 21, Carboxylic Acid Derivatives

L9-1

CHEM 8B, Lecture 9 Carboxylic Acid Derivatives: Acid Chlorides, Anhydrides, Esters, & Amides - Nomenclature - Nucleophilic Acyl Substitution (NAS) - Addition of Grignards – another combo mechanism (NAS + Nuc Add’n)

NUCLEOPHILIC ACYL SUBSTITUTION (NAS)

REACTIVITY SERIES (TOWARD NAS)

9 2I

not always0 LG Hd

itonl.ooqfcwfatgi.dk

it

i ii

ROH OR poorLG

ROH LG

NR not LGHNRz aHNREOKLGRcorltkasteact.ve

Page 2: UCLEOPHILIC A SUBSTITUTION 9...2019/08/08  · Chapter 21, Carboxylic Acid Derivatives L9-1 CHEM 8B, Lecture 9 Carboxylic Acid Derivatives: Acid Chlorides, Anhydrides, Esters, & Amides

Chapter 21, Carboxylic Acid Derivatives

L9-2

NOMENCLATURE CARBOXYLIC ACIDS NITRILES butanoic acid benzoic acid butanenitrile

ACID CHLORIDES butanoyl chloride benzoyl chloride

ANHYDRIDES butanoic anhydride benzoic anhydride

Butanoic benzoic anhydride ESTERS butyl butanoate butyl benzoate phenyl benzoate

AMIDES Butanamide N-methyl-N-phenylbenzamide

CARBONYL OUTSIDE A RING Cyclopentane carbaldehyde cyclopentane carboxylic acid

methyl cyclopentane carboxylate N-ethyl cyclohexane carboxamide

7 4

NCNO

7 a

symmetric o

whobutyl

IEEE on EIKOphtoph

Effidemide YEH's zoamide

5 I 5 l

ester

of pit 31mF

back 1113

Page 3: UCLEOPHILIC A SUBSTITUTION 9...2019/08/08  · Chapter 21, Carboxylic Acid Derivatives L9-1 CHEM 8B, Lecture 9 Carboxylic Acid Derivatives: Acid Chlorides, Anhydrides, Esters, & Amides

Chapter 21, Carboxylic Acid Derivatives

L9-3

NUCLEOPHILIC ACYL SUBSTITUTION (NAS)

Acidic NAS Mechanism - Fischer Esterification

- Try on your own: Acidic amide hydrolysis

Neutral NAS Mechanism (just add water!) - Acid Chloride Hydrolysis

- Try on your own: ester from acid chloride

OH

O+

HO

H2SO4 (aq)

D O

O+ H2O

5 aI

protofansfer

acidic PT9copyltranslate

fromL8 FT n

Ee i NASI 2

ii ii iig

902 U GPT

H i PiggyB

qii ii

Page 4: UCLEOPHILIC A SUBSTITUTION 9...2019/08/08  · Chapter 21, Carboxylic Acid Derivatives L9-1 CHEM 8B, Lecture 9 Carboxylic Acid Derivatives: Acid Chlorides, Anhydrides, Esters, & Amides

Chapter 21, Carboxylic Acid Derivatives

L9-4

Basic NAS Mechanism - Amides from Acid Chlorides

- Try on your own: Basic hydrolysis of esters

Imagine the possibilities!

Fill in the reagent(s) needed to complete each transformation above.

Cl

O

NaOH

H2NMe

NHMe

O

OH

O

OCH3

O

NHCH3

O

Cl

O

O

O

OH

O

OCH2CH3

O

N(CH3)2

O

O

OH

O

Nucleophilic Acyl SubstitutionReactions

OH

O

OOH O_0

odfqg aHzNMe

jNMe 9

HooIY oµeV o_0

Liter AaoHNMe

H o_O t CHIH0nucrG i eoI

mostreactive

go.fi EreHogreat

H2Ohydrolysis

H2O

CH3OHAtois HOT H2O

CatalystHt orOOHHzNCH3 excess

DCL HNMer H2ODcatalyst

specialreagent amide Ht or00A

more iffy

Page 5: UCLEOPHILIC A SUBSTITUTION 9...2019/08/08  · Chapter 21, Carboxylic Acid Derivatives L9-1 CHEM 8B, Lecture 9 Carboxylic Acid Derivatives: Acid Chlorides, Anhydrides, Esters, & Amides

Chapter 21, Carboxylic Acid Derivatives

L9-5

Adding Grignards & Hydrides to Acid Derivatives

TMT – Chapter 17 – addition to esters

Grignards and LAH add to (almost) all the acid derivatives to make the same product!!!

O

O

ethyl acetate

1. PhMgBr

2. H3O+

1. LiAlH4

2. H3O+

9 to

gy AIG

µ f

pyoaldehyde ketoneµ0

E Eai

NRas

Page 6: UCLEOPHILIC A SUBSTITUTION 9...2019/08/08  · Chapter 21, Carboxylic Acid Derivatives L9-1 CHEM 8B, Lecture 9 Carboxylic Acid Derivatives: Acid Chlorides, Anhydrides, Esters, & Amides

Chapter 21, Carboxylic Acid Derivatives

L9-6

Making Ketones with Mr. Grignard and Mr. Gilman (we missed you)

Ketones from nitriles (Chapter 20)

Ketones from acid chlorides

SUMMARY pilgBr H HO arDuc LAHlings gtfo arXat

ofRacaciR

Page 7: UCLEOPHILIC A SUBSTITUTION 9...2019/08/08  · Chapter 21, Carboxylic Acid Derivatives L9-1 CHEM 8B, Lecture 9 Carboxylic Acid Derivatives: Acid Chlorides, Anhydrides, Esters, & Amides

NAS Try on your ownHE

Huo

racyH2

s joy tHzNHz T

E mme sc i ne siotJmlGoekItii4ester a

Cephile q

Gsc

gNaootnuaE IootcHs0H

G asc