General structure Carboxyl group...SCH 206 Dr. Solomon Derese Carboxylic acids General structure R O...

SCH 206

Dr. Solomon Derese

Carboxylic acidsGeneral structure

R O

O

H

Carboxyl group

Acidic

R= alkyl, alkenyl, alkynyl or aryl

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The word carboxy (for a COOH group) is derived fromcarbonyl (C=O) + hydroxy (OH).

SCH 206

Dr. Solomon Derese

R O

O

H

Carbonyl

Hydroxyl

Structurally related to both carbonyl(aldehydes/ketones) and alcohol functional groups.

As a result their properties are related to thesefunctional groups.

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Structure and Physical Properties of Carboxylic Acids

SCH 206

Dr. Solomon Derese

The properties of carboxylic acids depends on thecarbonyl and the hydroxyl group and theirinteraction.

d

d

Basic site

Nucleophilesattack here

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SCH 206

Dr. Solomon Derese

The carboxyl group is stabilized by resonance relativeto the carbonyl group in aldehydes and ketones, andis therefore, less reactive.For these reasons, many reagents that react with thecarbonyl group of aldehydes and ketones react moreslowly or only in the presence of catalysts whenattacking the carbonyl group of carboxylic acid.

The –OH group is electron donatingthere by making the carbonyl carbonless electrophilic compared to thecarbonyl group of aldehydes andketones, therefore, less reactive.

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SCH 206

Dr. Solomon Derese 21

Just like alcohols, carboxylic acids are stronglyassociated due to hydrogen bonding.

d+

d+d-

d- d+d-

Hydrogen bonding in alcohols

High boiling

The melting and boiling points of carboxylic acids areamong the highest known for comparable weightbecause of extremely strong hydrogen bonding.

Carboxylic acids are similar in some respects to bothaldehydes/ketones and alcohols.

SCH 206

Dr. Solomon Derese

Carboxylic acid dimer

This is because a pair of carboxylic acid moleculesare held together not by one but by two hydrogenbonds and as a result exist as cyclic dimers.

H-bonding

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d-

d+

d+

d- d-

d-

In the liquid state a mixture of hydrogen bondeddimers as well as higher aggregates is present.

SCH 206

Dr. Solomon Derese

Examples

Propyl alcohol

M. Wt = 60

CH3 O

O

H

Acetic acidM. Wt = 60

b.p. = 97°C b.p. = 118ºC

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In aqueous solution hydrogen bonding betweencarboxylic acids is replaced by H-bonding betweencarboxylic acid and water. As a result of thiscarboxylic acids of four or fewer carbon atoms aremiscible in water in all proportions.

SCH 206

Dr. Solomon Derese

Acidity of carboxylic acids

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As their name implies carboxylic acids are acidic.They are the most acidic among compounds thatcontain only carbon, hydrogen and oxygen.Dissociation/Ionization of an acid

Hydrochloric acid (HCl) undergoes 100% ionization. Carboxylic acids are weak acids, for example a 0.1 Msolution of acetic acid in water, is only 1.3 % ionized.

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Bronsted – Lowry’s definition: An acid is a protondonor

O]H][H[RCO]O][H[RCOK

22

32eq

For a dilute aqueous solution, the concentration ofwater is essentially constant (≈55M)

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H][RCO]O][H[RCOO][HKK

2

322eqa

Acidity constant (a measure of the strength of an acid)

Acid strength is defined as the tendency to give up aproton.

aa logKpK The larger the value of pKa, the weaker the acid.Acetic acid for example has a pKa of 4.8. Althoughmuch weaker than mineral acids, carboxylic acids arenevertheless much stronger acids than alcohols. ThepKa of ethanol is for example 16.

The higher the value of Ka, the stronger the acid.

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What determines the strength of acids?

Examples

pKa = 16

pKa = 4.75

Base Conjugate base Conjugate acidAcid

SCH 206

Dr. Solomon Derese

Factors affecting the strength of an acidI. The electronegativity of A in H-AThe more polarized the bond the weaker the bondand stronger the acid.Examples

pKa = 16

pKa = 50

In a covalent single bond between unlike atoms theelectron pair forming the d bond is never sharedequally between the two atoms, it tends to beattracted more towards the more electron negativeatom of the two. This is called the inductive effect.

d+d-

<

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Weak/polar bond

1034 times more acidic!!!

SCH 206

Dr. Solomon Derese

In both ethanol and acetic acid, the O-H bond ispolarized by the greater electronegativity of theoxygen atom.

CH3 CH2 O H CH3 CO

O Hd+d-

<d+d-

<d+

d-

The key to much greater acidity of the acetic acid,is the powerful electron-attracting inductive effectof the carbonyl group (C=O) when compared withthe CH2 group in the corresponding position ofethanol.

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<

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II. Stability of A:- relative to A-H

A. Inductive Effect

The electron attracting inductive effect of thecarbonyl carbon stabilizes the acetate ion byattracting electrons away from the oxygen therebystabilizing the acetate.

In the case of the ethoxide the negative charge islocalized on the oxygen making it very unstable.

d+

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b) Resonance effect

Resonance effect also contribute to the increase acidity ofacetic acid relative to ethanol.

No resonance stabilization

No resonance stabilization

An alcohol dissociates to give an alkoxide ion, in which thenegative charge is localized on a single electronegativeatom.

Resonance leads to stability. Generally speaking, the largerthe number of resonance forms, the more stable asubstance is because electrons are spread out over a largerpart of the molecule and are closer to more nuclei.

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The two resonancestructures are not equivalentand the lower structurerequires charge separation,and therefore unstable.

The two resonancestructures are equivalentand no charge separation

Large resonance stabilizationSmall resonance stabilization

H3C

O

O

HH3C

O

O

This differential stabilization drives the equilibriumforward.

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There is effective delocalization, with consequentstabilization, in the acetate (carboxylate) anion as it hastwo resonance forms of equal energy, and thoughdelocalization can take place in the acetic acid molecule,this involves separation of charges and willconsequently be much less effective as a stabilizinginfluence because the resonance forms are not equal inenergy.The effect of this differential stabilization somewhatdiscourage the recombination of proton with thecarboxylate anion, the equilibrium as a result isdisplaced to the right, and therefore acetic acid is, byorganic acids standard a moderately strong acid.

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Substituent Effects on Acidity of Carboxylic Acids

Any factor that stabilizes the carboxylate anion relativeto the undissociated carboxylic acid will drive theequilibrium forward and results in increased acidity.Conversely, any factor that destabilizes the carboxylaterelative to the undissociated acid will result in decreaseacidity.An electron withdrawing group (EWG) attached to thecarboxyl inductively withdraw electron density, thereby,stabilizing the carboxylate anion and increasing acidity.

Carboxylate anion Undissociated carboxylic acid

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Any effect that result in electron-withdrawal froma negatively charged center is stabilizing effectbecause it spreads the charge and consequentlydecrease the electron density.

pKa = 4.75 2.85 1.48 0.64Acidity

EWG reduces the negativecharge on the carboxylate ionmaking it less reactive/stable.

SCH 206


pKa = 1.68pKa = 2.85

The more electronegative the substituent, the stronger theacid.

F is more electronegative than Cl.pKa = 2.8 2.6

The nitro group is a stronger EWG than Cl.

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Since inductive effects operate through d bondsand are dependent on distance, the effect ofsubstituent decrease as the substituent is movedfurther from the carboxyl.

pKa = 4.52 4.1 2.86

The closer the electron-withdrawing group to COOH,the stronger the acid.

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An electron-donating group (EDG) should haveexactly the opposite effect, destabilizing thecarboxylate anion and decreasing acidity.

pKa = 5.05 4.86 4.88 4.75 3.75

EDG increases the negativecharge on the carboxylate ionmaking it more reactive(unstable).

An alkyl group is a weak Electron Donating Group.

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This is because, the carbon becomes moreelectronegative (EWG) as its “S” character increase.

pKa = 4.75 4.3 4.2 1.8

The hybridization of the group that is directlyattached to the carboxyl group affect its acidity.

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Benzoic acid is astronger acid thanacetic acid. Theacidity ofsubstituted benzoicacid derivativesdepends on the EWnature of thesubstituent and theposition ofattachment.

pKa

Substituent (Y) Ortho Meta Para

H 4.2 4.2 4.2

CH3 3.9 4.3 4.4

F 3.3 3.9 4.1

Cl 2.9 3.8 4.0

CH3O 4.1 4.1 4.5

NO2 2.2 3.5 3.4

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Strong Inductive effect Medium Inductive effect Weak Inductive effect

Resonance effect Resonance effectNo resonance effect

pKa = 2.2 3.5 3.4

Resonance contribution having a positive charge atthe carbon atom bearing the carboxylate anion canbe written for the ortho and para isomers ofnitrobenzoic acid, whereas the nitro group in themeta position exerts primarily an inductive effect.

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This resonancecontributor puts apositive charge onthe carbon atom towhich thecarboxylate ion isbound

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Assignment 19I. Arrange the compounds in each of the following sets in

increasing order of acidities. Give reasons for youranswers.

a) 3-Chloropentanoic acid; 2-Chloropentanoic acid; 4-Chloropentanoic acid; pentanoic acid; 5-Chloropentanoicacid

b) Propanoic acid; 2-Methylpropanoic acid; 2,2-Dimethylpropanoic acid

c) 2-Methoxybutanoic acid; 3-Chlorobutanoic acid; 4-Iodobutanoic acid

d) Benzoic acid; p-Nitrobenzoic acid; p-Methoxybenzoicacid

e) p-Nitrobenzoic acid; Acetic acid; Benzoic acid

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II. Some pKa data for simple dibasic acids are shown. Howcan you account for the fact that the difference betweenthe first and second ionization constants decreases withincreasing distance between the carboxyl groups.

III. The following pKa values have been measured. Explainwhy a hydroxyl group in the para position decreases theacidity while a hydroxyl group in the meta positionincreases the acidity.

Name Structure pKa1 pKa2

Oxalic acid HO2CCO2H 1.2 4.2Succinic acid HO2C(CH2)2CO2H 4.2 5.6Adipic acid HO2C(CH2)4CO2H 4.4 5.4

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IV. Arrange the following compounds in increasingorder of acidity. Explain.

SCH 206

Dr. Solomon Derese

Preparation of carboxylic acidsOxidation

Oxidation of alkylbenzenes

RO

O

H

[O]

R = Alkyl

Most commonly used oxidizing agent are hot:or

CH3

O

O

H

KMnO4 (HOT)

H2O, HEAT

Example

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This show how the aromatic ring is stable. Thebenzene ring is inert to the oxidizing agents.

SCH 206

Dr. Solomon Derese

The mechanism of side chain oxidation is complexand involves the attack on C-H bonds at the positionnext to the aromatic ring to form benzylic radicalintermediates.

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No reaction

SCH 206

Dr. Solomon Derese

KMnO4/NaCr2O7/K2CO3

H2O2, NaOH, H3O

or

i. O3

ii. Ag2O,-OH or

Oxidative cleavage of alkenes

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Oxidation of primary alcohols

RCH2OHR

O

O Hi. KMnO4, -:OH, Heat ii. H3O+

ORCrO3, H2O, H2SO4 (Jones reagent)10

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XR

Na C N SN2

Alkyl halide

Hydrolysis of nitrites

Methyl, primary alkyl halide

This method works with primaryhalides, since competitive E2elimination can occur when secondaryand tertiary halides are used.

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Examples

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Hydrolysis of cyanohydrins

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Mechanism of acid hydrolysis of nitriles

C NR

H

OH

HC NR

H

OH H

OH

H

C NR

H

OH H

OHH

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O C O

Carboxylation of Grignard reagent

In order to use the Grignard method, the alkyl halideused to prepare the Grignard MUST NOT contain anyexposed functional groups that react with a Grignardreagent or inhibit its formation, i. e., OH, NH, SH,C=O, S=O, N=O, C≡CH, C≡N, epoxide.

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II. Which method - Grignard carboxylation or nitrilehydrolysis would you use for each of the followingreactions? Explain your choice.

I. Write the mechanism for basic hydrolysis of nitrile.

Assignment 20

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III. Identify the missing reagents a – f in thefollowing scheme:

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General structure Carboxyl group...SCH 206 Dr. Solomon Derese Carboxylic acids General structure R O...

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