ORCHEMII_CarbAcnDerivs

7/28/2019 ORCHEMII_CarbAcnDerivs

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CHAPTER 7CARBOXYLIC ACIDS

AND THEIR DERIVATIVES

Objectives: Determine the namesusing structures and structures

using names, and Describe and explain the properties

Describe, explain and predict the

preparation methods and thereactions of carboxylic acids andtheir derivatives.


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7.1. Structure

R OH

O

R OR'

O

R O

O

R'

O

R NR'2

O

R X

O

Carboxylic Acids Esters Anhydrides

Amides Acid Halides

R, R' = Carbon structuresAmides: R' = H or C structuresX = Halogens: F, Cl, Br, I.


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7.2. Nomenclature Carboxylic Acids: Read 20-2, pg 935

Esters: Read # 21-2A, pg 979

Amides: Read # 21-2B, pg 980

Acid Halides: Read # 21-2D, pg 982

Acid anhydrides: Read # 21-2E, pg983

Spectroscopy: read # 21-4, pg 988


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7.3. Properties a. Physical Properties

* Carboxylic Acids: Read # 20-3, pg

939 Derivatives: Read 21-3, pg 985

b. Spectroscopy

* Carboxylic Acids: Read #20-7, pg949

* Derivatives: Read #21-4, pg 988


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Acidity (Examples)O

OH

O

O(-)(+)Na

+ NaOH -----> + H2O

Ethanoic

acid Sodium ethanoate

O

OH

O

O(-)(+)NH4

+ NH3

Ammonia

Ammonium propanoatePropanoic acid


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Acidity Measurement Acids Ionize in waterRCO2H + H2O --------> RCO2(-) + H3O(+) Measure of acid strength =

Ka = [RCO2-][H3O+] / [RCO2H] = dissociationconstant

of an acid. Ka values are usually small and hard tomeasure

Remedy = pKa = -logKa Examples : acid Ka pKa

acetic 1.8E-5 4.7 (3)oxalic 6.23E-2 1.2 (1)Benzoic 6.5E-5 4.2 (2)


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Substituent Effects on

Acidity Acidity of R-CO2H depends on the

properties of substituent R.

Reference: H-CO2H General Rules

Electron donatingsubstituents

decreasethe acidityElectron withdrawingsubstituents

increasethe acidity


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Acidity (Examples)

OH

O

H

HH

OH

O

Cl

HH

OH

O

Cl

H

Cl

OH

O

Cl

ClCl

OHO OHO

O

OHO

NO2

OHO

NO2

OHO

NO2

pKa = 4.74 pKa = 2.86 pKa = 1.26 pka = 0.64

pKa = 4.19 pKa = 4.46 pKa = 3.47pKa = 3.41 pKa = 2.16


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Acidity (Exercises)Answer questions 20-3 a-c(*), pg 944


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6.4. Preparation a. Carboxylic Acids *1. Oxidation of primary Alcohols Substrate: R-CH2-OH. Reaction site: C carrying the

OH group. Reagent: Oxidizing reagent. Most used:* compounds of Mn(VII). Example: KMnO4* compounds of Cr(VI). Active ingredient: H2CrO4.

Forms:- Na2Cr2O7 in sulfuric acid (Jones Reagent)- Na2Cr2O7 in acetic acid Reaction: oxidation of the reaction site


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Oxidation of primary

Alcohols (Examples)

O

O O

O

R OH

R OH

O

OH ----------> OH

H ------->

KMnO4 H

Jones reagent

H2CrO4

(KMnO4)


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Oxidation of primary

Alcohols (Exercises)Answer Questions 20-35e & g, pg 972


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*2. Carboxylation of

Grignard Reagents Substrate: CO2. Reaction site: C. Reactive

property: electrophilic. Reagents: * R(-)(+)MgX(Grignard reagent) R(-) is a

nucleophile. Binds to C of CO2. Result: acarboxylate anion

*Acid: source of H(+). Provides the H to O

of the carboxylate. Reaction: Nucleophilic addition Product: carboxylic acid


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Carboxylation of Grignard

Reagents (Illustration)O C O

O

O

O

O O

1. R(-)(+)MgX

---------> R OH

(-)R

H3O+

Cl

MgCl(+)Mg

CO2

Cl(+)Mg

O OH

H3O+

2. H3O+

(+)MgX

(-) (-)


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*3. Oxidation of Alkenesand Alkynes

Substrate: Alkene / Alkyne. Rxn site:C=C or CC bond

Reagent: KMnO4, Oxidizing agent,source of O atoms

Products: * Carboxylic acids for the

side of the C=C bond carrying a H* Ketones for the side of the C=C bondwithout a H


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*3. Oxidation of Alkenes /Alkynes (Illustration)

HR3

R1

R2 R1

O

O

H

H

H

R2 R3

R1 O

O

H

R2 R3

O

H O

O

H

H

H

O

O

H

O

KMnO4

KMnO4


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Oxidation of Alkenes /Alkynes (Exercises)

Answer Questions 20-35 D & G, pg 972


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*4. Ozonolysis of alkynes

Substrates: Alkynes. Rxn site: C-Ctriple bond.

Reagents:

* Ozone. Binds the Os to the CC bond.

* Water. Provides the necessary Hs toform the expected carboxylic Acids.


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Ozonolysis of Alkynes (Illustration)

R1 R2 R1R2

O

O

R1 O

O

H R2 O

O

H

O

OH

O

OH

+

+1. O3

2. H2O


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*5. Oxidation of Side-chainsof Aromatic Compounds

Substrates: Alkylated aromaticcompounds

Reagents: Oxidizing agents. Mostcommon: Mn(VII) as in KMnO4 andCr(VI) as in H2CrO4.

Reaction: oxidation of the C next tothe aromatic ring to a CO2H group.

x a on o e c a ns o


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x a on o e-c a ns oAromatic Compounds(Illustration)

R

z

OH

O

z

OH

O

Na2Cr2O7, H2SO4, heat

or KMnO4, H2O, heat

1. KMnO4, KOH/H2O, heat

2. HCl

Z = non-oxidizable substituent in any position on the ring


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Preparation of Carboxylicacids (Exercises)

Answer the following questions:

20-11 a-c, pg 955


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*6. Formation andHydrolysis of Nitriles

Substrates: alkyl halides. Reaction site: Cthat carries the halogen. Reactive property:electrophilic.

Reagents:* compounds of cyanide (CN(-)) ion:

nucleophile. CN(-) replaces the halogen onthe electrophilic site. Result: fomration of a

nitrile* Acidic or basic H2O. Brings O and OH to the

C of the CN group. Result: carboxilic acid.


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Formation and Hydrolysisof Nitriles (Illustration)

R O

O

H

BrCN

O

OH

R-X + Na(+)(-)CN R-CN

H(+)/H2O

or HO(-)/H2O

NaCNH3O(+)


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Formation and Hydrolysisof Nitriles (Exercises)

Answer Questions: 20-35 a & b, pg 972


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b. Preparation of Esters(R-CO-OR)

*1. Fischer esterification

Substrates: R-CO2Hs. Reaction site: C of C=Ogroup. Reactive property: electrophile

Reagents: R-OHs. Nucleophile: O. The O binds tothe C of the C=O group and replaces the OH group.

Reaction conditions: presence of an acid> TheH(+) of the acid help: (1) in making the electrophile

available; (2) removing the OH of the R-CO2H. Reaction: nucleophilic substitution of OH by OR on

the CO2 group.


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Fischer Esterification(General Pathway)

R O

O

H R'O

H

R O

O

R'

R'O

H

R O

O

H

H

R O

O

R'

H

H(+)

H2O+:

:..

..

:(+)

:

(+)

H2O+

- H(+)


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Fischer Esterification(Examples)

O

O

O

O

O

O

O

O

H

+ CH3OH ---->

H2SO4

OH

H

HCl


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Fischer Esterification(Exercises)

Answer questions

* 20-35 j, pg 972

* 21-48 c, pg 1033


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c. Preparation of AcidHalides (R-CO-X)

Substrates: R-CO2H. Rxn site: C ofC=O. Reactive property: electrophile

Reagents: sources of halogens (X).Most common: SOCl2, COCl2

Reaction : Nucleophilic substitution of

OH of R-CO2H by X.


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Preparation of AcidHalides (General Pathway)

R O

OH

R O

Cl

SClCl

O

R O

OH

SO(-)Cl

ClR O

OH

SO

Cl

Cl

:

..

:

..

SO2 HCl+ +

:(+)

.. ..

: :


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7.5. Reactions

a. Carboxylic Acids

Types of reactions:

* Reactions with bases. Result Carboxylic acid salts

* Reactions with nucleophiles. Electrophile: C of C=Ogroup

* Reactions with electrophiles. Nucleophile: O of OHgroup.

*1. Reactions with bases

Read 20-5, pg 944


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*2. Reduction of Carboxylicacids to primary alcohols

Substrate: R-CO-OH Site: C of C=O

Reagents:

* Source of H(-) (the nucleophile). Most common

sources: BH3 (best), LiAlH4. BH3 reacts with C=Ogroup of CO2H preferentially to C=O of Aldehydes /Ketones. H(-) binds to C of C=O group. Result:Aldehyde which react with one more H(-). Ultimateresult: alkoxide

* Acidic watersolution: source of H(+). H(+)sbinds to the alkoxide. Result: primary alcohol

Reduction of Carboxylic acids to


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Reduction of Carboxylic acids toprimary alcohols (GeneralPathway)

R H

O

O

OH OH

1. BH3

2. H3O

+R R

O(-)

O2-

RH

H

H(-)

H(-)

+

H3O+

O

O(-)R

H(-)


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Reduction of Carboxylic acids toprimary alcohols (Examples)

O O

O OH

O

OH OH

1. BH3

2. H3O+

O

OH

1. LiAlH4

2. H3O+


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Reduction of Carboxylic acids toprimary alcohols (Exercises)

Answer questions 20-19 a and c, pg965.


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*3. Conversion of CarboxylicAcids to tertiary alcohols


Reagents: * Sources of C nucleophiles.

Most common:Alkyl lithium (R(-)(+)Li)andGrignard reagents (R(-)(+)MgX).Nucleophiles bind to C of C=O group.

Ultimate result: Tertiary alkoxides.

* Acidic water. Source of H(+). H(+) binds totertiary alkoxide.

Products: Tertiary alcohols


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Conversion to tertiaryalcohols (General Pathway)

O

OH

1. R'(-)(+)MgX

2. H3O+

R

R

O(-)

RR'

R'

R'(-)

H3O+

O

R

R'(-)

OH

R'

R' R'

O

R O(-)R'(-)

H2O+

R'-H+


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Conversion of CarboxylicAcids to Ketones


Reagents: Sources of C nucleophiles.

Most common:Alkyl lithium (R(-)(+)Li)andGrignard reagents (R(-)(+)MgX).Nucleophiles bind to C of C=O group.

Reaction Condition: Use no more that 2

equivalents of reagent.

Products: ketones


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Conversion to Ketones(General Pathway)

O

RR'(-)

O

ROH

R'

O

R O(-)R'(-)

R'-H+


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Conversion to Ketones(Example)

OO

2 CH3Li

OH

Extra exercise: #20-21 a, pg 965


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b. Reactions of CarboxylicAcid Derivatives

*1. Nucleophilic Substitutions Substrates: R-CO-X. X = halogen, OR,

NR2, O-CO-R. Most reactive: acid

halides. Reaction site: C of C=O. Reactiveproperty: electrophile.

Reagents: any nucleophile. Nucleophilereplaces the X on the C=O group.

Products: R-CO-Nu. The high reactivity ofR-CO-X(as a halide)and the wide varietyof nucleophiles lead to a wide variety ofproducts

uc eop c u s u ons o


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uc eop c u s u ons oAcid Halides (GeneralPathway)

O

OH

O

O O

N

O

O

X

O

OHH2O

R R

O

OR'RR'-OH

R'

RR'

(R')2NH

R'

R'


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Nucleophilic Substitutionsof Acid Halides (Examples)

Cl

OO

OH

O

O

O

Cl

OOH

O

O

Cl

O NH2

NH

O



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uc eop c u s u ons oOther Carboxylic AcidDerivatives

Other carboxylic acid derivatives reactsimilarly but less readily compared

to acid halides



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uc eop c u s u ons oCarboxylic Acid Derivatives(Exercises)

Answer to Questions

* 21-48 a & b, pg 1033

* 21-50 a, b, d, g, pg 1035


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a. e uc on o car oxy c


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a. e uc on o car oxy cAcid Derivatives to primaryalcohols

Substrates: R-CO-X Reaction site: C of C=O

Reagents: * Source of H(-) (the nucleophile).Most common sources: LiAlH4 (LAH) . The H(-) binds

C of C=O group. Ultimate result: primaryalkoxides.

*Acidic water. Source of H(+) which binds to thealkoxides.

Products: primary alcohols. Note: Mild reagents: used to form adehydes.

Example: LiAlH(t-butoxide)3 (LTTBAH)


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Reduction to primaryalcohols (General Pathway)

O

OH1. LiAlH4

2. H3O+

R R

O(-)

RH

H

H3O+

O

R

H(-)

X

H

H(-)

d i i


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Reduction to primaryalcohols (Examples)

O

H

O

OH

1. LAH

2. H3O+

ClNote:Aldehydes can be obtained by using mild reducing agents like LiAlH(tBuO)3 (LTTBAH)

O 1. LTTBAH

2. H3O+

Cl

R d i i


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Reduction to primaryalcohols (Exercises)

Answer question 21-50 e & f, pg 1034


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Acid Derivatives to TertiaryAlcohols (Examples)

O OH1.CH3MgBr

2. H3O+

Cl

NOTE: using alkylcuprates instead of grignard reagents produces ketones.Dialky cuprates do not react with esters or anhydrides.

O

Cl

O

(CH3-CH2(-))2(2+)CuLi

H3O+


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Acid Derivatives to TertiaryAlcohols (Exercises)

Answer Questions:

* 21-54 d, pg 1034

* 21-55, pg 1035

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