Chapter 20: Carboxylic Acids & Nitriles

Carboxylic Acids

C=O + OH on the same carbon

The functional group is:

–CO₂H or –COOH

Carboxylic acids can also be:

• reduced → alcohols

• dehydrated → acid anhydrides

Naming Carboxylic Acids

IUPAC Rules

1. Find longest Carbon chain containing the COOH carbon

2. The carboxylic acid carbon is automatically Carbon #1

3. Change -e to -oic acid

The COOH carbon is always Carbon #1

Carboxylic Acid Properties

Acidic because they can lose H+, the product is a carboxylate ion

When an acid loses H+, the negative charge can be distributed over both Oxygens. The two resonance structures are equivalent. The negative charge can be distributed over both oxygens. The two resonance structures are equivalent.

Result:

The negative charge is spread out —> more stable conjugate base —> more acidic starting molecule.

Acidity Rule

More stable conjugate base = stronger acid

This means that carboxylic acids are much more acidic than alcohols

Carboxylate:

negative charge delocalized over TWO oxygens

Alcohol conjugate base:

negative charge localized on ONE oxygen

Going RIGHT and DOWN generally increases acidity.

Ka and Pka

Higher Ka = stronger acid

pKa is -log ka, so:

Lower pKa = stronger acid

Higher pKa = weaker acid

Carboxylic acid dimers

Two carboxylic acid molecules interact through two hydrogen bonds. This strong association affects physical properties such as boiling point.

Water Solubility

Carboxylic acids can hydrogen bond with water. Short chain acids are relatively soluble. As the carbon chain becomes longer, solubility decreases.

Henderson-HasselBalch Equation

see image

Substituent Effects on Acidity

Substituents can make an acid:

• more acidic

• less acidic

Electron-withdrawing groups (EWGs) increase acidity. (Why?) They pull electron density away and stabilize the negative charge of the conjugate base.

INDUCTIVE EFFECT

EWG → stronger acid

• More electronegative substituent → more acidic

• More EWGs → more acidic

• EWG closer to acidic group → more acidic

An EWG immediately next to COOH has a stronger effect than one farther away.

Resonance Effects of EWG’s

EWGs can also stabilize negative charge through resonance when the structure allows it. This is particularly important with aromatic systems.

Using pKa to identify EWG/EDG

If a substituted benzoic acid has a: LOWER pKa than benzoic acid

The substituent is likely: Electron withdrawing Because it makes the acid stronger.

If pKa is higher: Electron donating, The substituent makes the acid weaker.

Preparing Carboxylic Acids: Oxidation of alkylbenzenes

If you have:

benzene—R

and the benzylic carbon has:

at least ONE H

Strong oxidation can convert the entire side chain into:

benzene—COOH

So:

Alkylbenzene → benzoic acid

Preparing Carboxylic Acids: Oxidation of Primary Alcohols

Primary alcohol:

RCH₂OH

↓

oxidation

↓

aldehyde

↓

further oxidation

↓

carboxylic acid

Reagents: CrO₃/H⁺ & Na₂Cr₂O₇/H⁺

Dess-Martin is not the reagent to use for this final oxidation; its role is stopping at the aldehyde.

Preparing Carboxylic Acids: Oxidation of Aldehydes

RCHO

↓ oxidation

RCOOH

Same important reagents:

CrO₃/H⁺

Na₂Cr₂O₇/H⁺

Preparing Carboxylic Acids: Nitrile Hydrolysis

A nitrile:

R—C≡N

can be hydrolyzed into:

R—COOH

Nitrile → carboxylic acid

The carbon skeleton is maintained.

Preparing Carboxylic Acids: Grignard + CO2

Grignard:

RMgX

reacts with:

CO₂

then acid workup.

Product:

RCOOH

Important:

This adds ONE carbon to the carbon skeleton.

Why?

Because the carbon from CO₂ becomes the carboxyl carbon.

Reactions of Carboxylic Acids

• Carboxylic acid → alcohol, using: LiAlH₄

• Carboxylic acid → acid anhydride, through dehydration.

Carboxylic acids have: RCOOH

The OH is a: poor leaving group

So you often need to activate the OH or convert it into a better leaving group before substitution-type chemistry can occur.

Nitriles

Functional group: –C≡N, Called: Cyano group

The nitrile carbon is electrophilic.

Therefore nitriles can undergo:

Nucleophilic addition

Preparing Nitriles

Alkyl halide → nitrile, Use: CN⁻. This is typically SN2. The carbon from CN becomes part of the molecules, therefore, Nitrile formation adds ONE carbon

Nitrile Hydrolysis

Nitrile → Amide → Carboxylic acid

Carbon skeleton does not change. The same nitrile carbon becomes the carboxyl carbon

Nitrile Reduction

Nitriles can be reduced. Nitrile → Primary amine. The carbon skeleton stays intact.

Nitrile + Grignard

Nitrile:

R—C≡N

reacts with:

R'MgX

The Grignard adds an R group.

After workup:

Ketone

Grignard adds a carbon containing group, giving a larger Carbon skeleton

IR Spec

Carboxylic Acid

C=O:

~1700 cm⁻¹

Strong peak.

But the OH is extremely broad.

Carboxylic acid OH:

~2500–3300 cm⁻¹

Alcohol OH:

~3600–3300 cm⁻¹

Usually broad.

Nitrile IR:

C≡N stretch:

~2200–2250 cm⁻¹

Usually a relatively sharp peak.

1 H NMR Carboxylic acid proton

The COOH proton appears very far downfield: > 11 ppm

summary (pt 1)

1. COOH = carboxylic acid

2. CN = nitrile

3. Lower pKa = stronger acid

4. Higher Ka = stronger acid

5. More stable conjugate base = stronger acid

6. Resonance stabilizes carboxylate

7. EWGs increase acidity

8. Closer EWG = stronger effect

9. pH = pKa → 50% HA / 50% A⁻

10. Alkyl halide + CN⁻ → nitrile

11. Nitrile hydrolysis → carboxylic acid

12. Nitrile hydrolysis keeps carbon skeleton the same

13. Grignard + CO₂ → carboxylic acid ONE carbon larger

14. Nitrile + Grignard → ketone

15. Nitrile reduction → primary amine

summary (pt 2)

Carboxylic acids = RCOOH.

They are acidic because their conjugate base, RCOO⁻, is resonance-stabilized. Lower pKa = stronger acid. Electron-withdrawing groups increase acidity, especially when they are close to COOH. Henderson–Hasselbalch: pH = pKa + log(A⁻/HA), and when pH = pKa, you have 50% HA and 50% A⁻.

Carboxylic acids can be made by strong oxidation of primary alcohols/aldehydes, oxidation of alkylbenzenes, nitrile hydrolysis, or Grignard + CO₂. Grignard + CO₂ adds one carbon.

Nitriles = R–C≡N. Alkyl halide + CN⁻ makes a nitrile and adds one carbon. Nitrile hydrolysis gives a carboxylic acid with the same carbon skeleton. Nitrile reduction gives a primary amine. Nitrile + Grignard gives a ketone with a larger carbon skeleton.

IR: C=O ~1700 cm⁻¹, carboxylic acid OH is very broad ~2500–3300 cm⁻¹, and C≡N is around 2200 cm⁻¹. In ¹H NMR, a signal >11 ppm strongly suggests a carboxylic acid proton.