Preparation and Reactions of Carboxylic Acids

Learning Objectives

1- Synthesis (preparation) of carboxylic acids by:

1.1 Oxidation of primary alcohol

1.2 Carboxylation of Grignard reagents

1.3 Hydrolysis of Nitriles

2-Reactions of carboxylic acids:

2.1 Neutralization

2.2 Reduction

2.3 Alkylation

2.4 Decarboxylation of β-dicarboxylic acids

Acid BaseIt donates hydrogen ions (H+) such as HCl, HNO3

CH3COOH

It accepts hydrogen ions (H+) such as NH3, CH3COO-, OH-

Acid base definitionsFirst Theory : Brønsted–Lowry acid–base theory

Acid + Base conjugate base + conjugate acid

HA + B A- + BA+

CH3COOH + H2O CH3COO- + H3O +

Second theory: Lewis definitions

Acid Base Lewis acid : electron pair

Acceptor Lewis Acids are Electrophilic

Lewis Base: Lone pair Donor Lewis Bases are Nucleophilic

Examples1. All cations are Lewis acids since they are able to accept electrons. (e.g., Cu2+, Fe2+ )

2. An atom, ion, or molecule with an incomplete octet of electrons can act as an Lewis acid (e.g., BF3,

AlF3).

3. Molecules that have multiple bonds between two atoms of different electronegativities (e.g., CO2, SO2)

Examples of lewis base are electron pair donors which include 1. simple anions, such as OH-,

CN-, RCOO- and F-

2. lone-pair containing species, such as H2O, NH3, CO

3. electron rich π-system Lewis bases, such as pyridine and benzene

Electrophile (El) Nucleophile (Nu)

-Electron deficient group accepting an electron pair-It can be neutral or positively charged- It has affinity to bond to a Lewis base or a nucleophile

-Electron rich group donating an electron pair- It can be neutral or negatively charged-It attacks the + charge on electrophile, or bonds to a Lewis acid

Because electrophiles accept electrons, they are Lewis acids

Because nucleophiles donate electrons, they are by definition Lewis bases

Examples : 1. Cations such as H+ and NO+

2. Neutral molecules such as HCl, Cl2 and Br2,

3. Carbon in alkyl halides, acyl halides, and carbonyl compounds

( e.g keton and ester)4. Carbon electrophiles in alkyls

Examples1. Anions, such as Cl-, CN-, and F-

2. lone-pair containing species, such as NH3

3. Carbon nucleophiles in the Grignard reagent (CH3 – MgBr) and organolithium reagent

(CH3 – Li).

4. Oxygen nucleophiles are H2O, OH-, RCOO−,

5. Sulfur nucleophiles: H2S,RSH, RS-

6. Nitrogen nucleophiles include ammonia, azide N3

-, amines, and nitrites.

Chemical group Typeproton (H3O+) electrophilealkyl halide (CH3-Br) electrophilealcohol (CH3-OH) electrophilealdehyde (CH3 - CHO) electrophileketone (CH3 - CO - CH3) electrophileacid chloride (CH3 - CO - Cl) electrophileester (CH3 - CO - OCH3) electrophile

boron trifluoride (BF3) electrophile

thionyl chloride (Cl - SO - Cl) electrophilephosphorous trichloride (PCl3) electrophile

chloride ion (Cl-) nucleophilehydroxide ion (OH-) nucleophilemethoxide ion (CH3O-) nucleophile

cyanide (CN-) nucleophileOrganolithium compound (CH3 - Li) nucleophile

Grignard reagent (CH3 - MgBr) nucleophile

amine (N(CH3)3) nucleophile

phosphine (P(CH3)3) nucleophile

pi bond (H2C = CH2) nucleophile

Common electrophiles and nucleophiles

Solution :a. Bromide ion:  This atom has four lone pairs and a formal negative charge, suggesting it is electron-rich and can therefore function as a nucleophile.  If it has none of the features that would suggest it might behave as an electrophile. b. Ammonium ion: This ion has a formal positive charge, suggesting it is electron-poor and can therefore function as an electrophile.  It has no lone pairs or negative charge, suggesting it will not function as a nucleophile. c. Water: The oxygen atom of water has two lone pairs and a δ - charge (oxygen is more electronegative than hydrogen).  This suggests that water can behave an a nucleophile.  Each hydrogen atom bears a δ + charge, so the molecule can behave as an electrophile as well.  Many molecules can be both nucleophiles and electrophiles.  How they behave depends upon what they react with. For example, if water is reacted with an electrophile, the water will behave as a nucleophile.

Example : Decide if each molecule or ion shown below will react as a nucleophile or electrophile, or both.

Examples of electrophile-electrophile reactions

Leaving Group LG

Examples of Leaving groups

What makes a Good Leaving Group ( LG)?As for acidity, the more stable A- is, the more the equilibrium will favour dissociation, and release of H meaning that HA is more acidic.For the leaving group, the more stable LG- is, the more it favours "leaving“, meaning that the better leaving group LG- is .

It is a group that tends- or favours -to leave with a pair of electronsIt can be neutral ( e.g NH3 & H2O) or anions ( OH-, halides)

Synthesis of Carboxylic acids

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• Carboxylic acids can be prepared by oxidizing primary alcohols or aldehydes. The oxidation of primary alcohols leads to the formation of aldehydes that undergo further oxidation to yield acids.

• The oxidation of ethanol produces ethanoic acid (acetic acid).

OH O O | [O] || [O] ||CH3—CH2 CH3—C—H CH3—C—OH

ethanol ethanal ethanoic acid(ethyl alcohol) (acetaldehyde) (acetic acid)

(1) oxidation of 1o alcohols

CH3CH2CH2CH2-OH + CrO3 CH3CH2CH2COOH n-butyl alcohol butyric acid 1-butanol butanoic acid

CH3 CH3

CH3CHCH2-OH + KMnO4 CH3CHCOOH isobutyl alcohol isobutyric acid2-methyl-1-propanol` 2-methylpropanoic acid

(1) oxidation of 1o alcohols

All strong oxidizing agents (potassium permanganate KMnO4 , potassium dichromate K2Cr2O7, and chromium trioxide CrO₃) can easily oxidize the aldehydes that are formed.

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(2) Carboxylation of Grignard Reagents

Grignard reagents react with carbon dioxide to yield acid salts, which, upon acidification, produce carboxylic acids.

Gringard reagent

Grignard reagents are strong nucleophiles reacting with electrophiles such as carbonyl compoundGrignard Reagents Increase the carbon chain by one carbon.Grignard reagents are also very strong bases and will react with acidic hydrogens (such as alcohols, water, and carboxylic acids).

hydrolysis

Step 1: The nucleophilic C in the Grignard reagent adds to the electrophilic C in the polar carbonyl group, electrons from the C=O move to the electronegative O creating an intermediate magnesium carboxylate complex.

Step 2:

Protonation of the carboxylate oxygen creates the carboxylic acid product from the intermediate complex.

NUCLEOPHILIC ADDITION OF RMgX TO CARBON DIOXIDE

( carbon in Gringard reagent is partly negative and magnesium is partly positive because the C is more elctronegative than Mg)

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Nitriles are compounds which contain cyanide ion CN- attached to a hydrocarbon group (R).

Cyanide ion is an excellent nucleophile and will react with alkyl halides to give nitriles. This reaction involves 2 steps and results in an increase in the length of the carbon chain because of the extra carbon in the -CN group. The nitrile can be hydrolyzed to a carboxylic acid

(3) Hydrolysis of Nitriles

hydrolysis

General Example

nitrile

Step 1. Nitriles are prepared by SN2 (Nucleophilic substitution ) reactions of alkyl halids ( R-X) with Sodium cyanide NaCN

Step 2. Hydrolysis of the nitriles yields a carboxylic acids (-C≡N is converted to –COOH)

Specific Examples

CH3-Br CH3-CN CH3COOH + NH4+

1.

2.

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Learning Check

What alcohol could be used to prepare the following:

1. butanoic acid

2. propanoic acid

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Solution

What alcohol could be used to prepare

the following: [O] [O]

1. butanol butanal butanoic acid

[O] [O]

2. propanol propanal propanoic acid

Reactions of Carboxylic Acids

Carboxylic acids are neutralized by strong bases to give carboxylate salts.

as long as the molecular weight of the acid is not too high, sodium and potassium carboxylate salts are soluble in water

Salts of Carboxylic Acids

1.Neutralization

strongeracid

weakeracid

RCOH + HO– RCO– + H2O

OO

1.Neutralization

salt

Fatty Acids; Carboxylic Acids (R-CO2H) where R

group contains 12-18 carbons.

Soaps/detergents; Salts of long chain fatty acids

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Micelles: substances with polar (hydrophilic) head groups and hydrophobic tail groups form aggregates in water with the carboxylate groups on the outside and nonpolar tails on the inside.

Steric acid

Micelles

CH3(CH2)16C

O

OH + NaOH CH3(CH2)16CO

O

Na+–

+ H2O

polarnonpolar

2.Reduction Reduction to a 1° alcohol

Use strong reducing reagent: LiAlH4.

It reduces carboxylic acid to alcohol.

Reduction to Aldehyde

• Difficult to stop reduction at aldehyde.• Use a more reactive form of the acid (an acid chloride) and a weaker reducing

agent, lithium aluminum tri(tbutoxy)hydride.

benzaldehyde

3.Alkylation to Form Ketones

React 2 equivalents of an organolithium reagent (e.g CH3-Li) with a carboxylic acid to produce keton.

CH2CH3

Benzoic acid Ethyl phenyl ketone

Decarboxylation: is loss of carbon dioxide, Reaction type: Elimination

most carboxylic acids, if heated to a very high temperature, undergo thermal decarboxylation

most carboxylic acids, however, are quite resistant to moderate heat and melt or even boil without decarboxylation

4. Decarboxylation

RH CO2RCOH

OSimple carboxylic acids do not decarboxylate readily

+

150°CCH3COH

O

+ CO2HOCCH2COH

O O

4. Decarboxylation

Carboxylic acids with a carbonyl group at the 3- (or β-) position readily undergo thermal decarboxylation, e.g. derivatives of malonic acid.

The reaction proceeds via a cyclic transition state giving an enol intermediate that tautomerizes to the carbonyl

Step 1: Remember curly arrows flow.... Start at the protonation of the carbonyl, break the O-H bond and form the p bond, break the C-C and make the C=C. Note the concerted nature of this reaction and the cyclic transition state.

Step 2: Tautomerization of the enol of the carboxylic acid leads to the acid product (not shown here).

4. Decarboxylation