Acids & Bases/ Organic Chemistry

Dr. Ron Rusay

Fall 2012

Chapter 3

Structure and

Bonding

Acids and Bases

Models of Acids and Bases

•Arrhenius: Acids produce H+ & bases produce OH ion in aqueous solutions .•Brønsted-Lowry: Acids are H+ donors & bases are proton acceptors.

•HCl + H2O Cl + H3O+

acid base

Comprehensive TutorialAcid & Base Principles in Organic Chemistry

Highly recommended viewing

http://chemconnections.org/organic/Movies%20Organic/acidsbases.mov

Acid-Base EquilibriumConjugate Acid/Base Pairs

HA(aq) + H2O(l) H3O+(aq) + A(aq) conj conj

acid base acid base•conjugate acid: formed when the proton is transferred to the base.•conjugate base: everything that remains of the acid molecule after a proton is lost.

http://chemconnections.org/organic/Movies%20Org%20Flash/ConjugateAcidBaseActivity.swf

QUESTION: 3.1Aniline, C6H5NH2, was isolated in the 1800s and

began immediate use in the dye industry. What is the formula of the conjugate acid of this base?

A. C6H5NH2+

B. C6H5NH3+

C. C6H5NH–

D. C6H5NH+

E. C6H5NH2

Weak Acids

• Weak acids are only partially ionized in solution.

or

• Ka is the acid dissociation constant.

HA(aq) + H2O(l) H3O+(aq) + A-(aq)

HA(aq) H+(aq) + A-(aq)

[HA]

]][AO[H -3

+=aK [HA]

]][A[H -+=aK

Organic Acids & Bases• Organic acids are weak acids, eg. Acetic

acid.• However, there can be substantial differences

in their relative strengths. What could you use to compare relative acidities?

• Organic bases are weak bases and relate to ammonia.

• However, there can be substantial differences in their relative strengths. What could you use to compare relative basicity?

Conjugates

Ka x Kb = ?

What do pKa and pKb refer to?pKa + pKb = ?

Remember: pH + pOH = pKw

Values for pKb are not commonly found in the reference literature.

Therefore, a comparison of relative basicity is made by using the pKa values of the corresponding conjugate acids.

Strengths of Bases from pKa Values

Which is the stronger acid?

Which is the stronger base?

QUESTION: 3.2

Use information on the table above to determine which of the following bases would have the weakest conjugate acid:

OC6H5–; C2H3O2

–; OCl–; NH3

A. OC6H5–

B. C2H3O2–

C. OCl– D. NH3

QUESTION: 3.3

Use information on the table above to determine the order of increasing base strength for the following bases:

OC6H5–; C2H3O2

–; ClO2–; NH3

A. OC6H5– < NH3 < C2H3O2

– < ClO2–

B. C2H3O2– < ClO2

– < NH3 < OC6H5–

C. ClO2– < C2H3O2

– < NH3 < OC6H5–

D. NH3 < OC6H5– < C2H3O2

– < ClO2–

Acid and Base Equilibria

The equilibrium favors the weaker of the acid vs. its conjugate acid or base vs. its conjugate. Weak wins!

http://chemconnections.org/organic/Movies%20Org%20Flash/acid-base-eq.swf

QUESTION: 3.4

CH3

C ≡ + CH

NH2

p Ka

=26

CH3

C ≡ C

+ NH3

p Ka

=36

CH3

CH3

+

NH2

p Ka

=50

CH3

CH2

+ NH3

CH3

C

O H

O

+ NH3

CH3

C

O

O

+ NH4

+ HCl CH3

OH

p Ka

= 15.5

– – + H Cl H CH3

O

+ HCl CH3

OH Cl + CH3

OH2

p Ka

=36

p Ka

=4.7

p K-a

=–7p K

a=–2.5

p Ka

=9

CH3

C

O H

O

+ NH3

O

+ NH2

p Ka

=36 p Ka

=–6

C H3

C O H2

pKa

< –15

Consider the following equilibria. Identify the weaker of the two: acid vs. its conjugate acid in each reaction. Which reactions favor formation of product?

1.

2.

3.

4.

5.

6.

A. All do: 1-6

B. 1, 4, 5

C. 2, 3, 6

D. 1, 5

E. None do.

Worksheet 5: Acids & Baseshttp://chemconnections.org/organic/chem226/226assign-12.html#Worksheets

Organic Acids & Bases• Organic molecules in context can be considered as

behaving relatively as weak acids or weak bases.• Formal Charge is important in considering which.• Knowing the Formal Charge allows a prediction.• (+) positive atoms behave acid-like, (-) negative

atoms behave base-like.

• This can be used in predicting how molecules will react--- or don’t react, and the products of reactions.

Formal Charge / Acids & BasesElectrophiles / Nucleophiles / Reactivity

CH

3

N

C H

3

C H

3

C H

3

CH3

N

C H3

..

CH

3

N

C H

3

C H

3

O

..

: :

:

CH

3

O

O

: :

..

:

:::

:

H O

..

:

:

C H

3

C H3

CH

3

C

C H

3

C H

3

CH3

C :

CH

3

C H3

C H3

O: :

..

:

H O H

H

:

CH

3

O H

C H3

..

CH3

O

C H2

: :

..

:

CH

3

O

..

:

:

CH3

O

C H3

H

:

C H2

Worksheet 1http://chemconnections.org/organic/chem226/226assign-12.html#Worksheets

Structure and Acid-Base PropertiesImportant factors that effect acidity in binary

compounds, eg HCl (having only two elements):

• Bond Length (shorter = stronger bonds; lower acidity)

• Bond Strength (longer = weaker bonds; higher acidity: more dissociation, more protons [hydronium ions] in solution)

• Bond Polarity (smaller e.n. differences favor higher acidities)

Electronegativity, Charge Density, Bond Polarity and Acid-Base Properties

Explain which is the stronger acid: HBr or HF.

HBr is a stronger acid than HF. The greater the e.n. difference, the more polar the bond, the shorter and stronger the bond, and since it is harder to dissociate (break), the weaker the acid.

Strength of Oxyacids(Three atoms: ternary vs. binary)

Induction or a ”Push-Pull” electronic effect influences the proton, which weakens the oxygen-hydrogen bond. Chlorine (higher e.n.) pulls electrons more

than Iodine (lower e.n.)

QUESTION: 3.5

• Rank 1.0M solutions of HBrO, HIO and HClO in order of increasing acidity.

HBrO , Ka = 2.1 x 10-8

HIO , Ka = 2.3 x 10-11

HClO , Ka = 3.0 x 10-8

A) HBrO < HIO < HClO B) HIO < HBrO < HClO

C) HClO < HBrO < HIO D) HIO < HClO < HBrO

Question: 3.6 True (A) / False (B)

• HBrO4 is a weaker acid than HBrO2.

• HClO2 , Ka = 1.2 x 10-2

• HBrO , Ka = 2.06 x 10-8

• HIO , Ka = 2.3 x 10-11

• HClO , Ka = 3.0 x 10-8

QUESTION: 3.7

• Rank 1.0M solutions of HBrO, HIO and HClO in order of increasing pH

HBrO , Ka = 2.1 x 10-8

HIO , Ka = 2.3 x 10-11

HClO , Ka = 3.0 x 10-8

A) HBrO < HIO < HClO B) HIO < HBrO < HClO

C) HClO < HBrO < HIO D) HIO < HClO < HBrO

QUESTION: 3.8• Use the concept of induction “push-pull”.

Rank the following organic acids in order of decreasing acidity from most acidic to least.

1) Br-CH2COOH 2) I-CH2COOH 3) CH3COOH

• A) 2 > 1 > 3 B) 3 > 2 > 1

• C) 2 > 3 > 1 D) 1 > 2 > 3

QUESTION: 3.9Rank the following acids in order of decreasing

acidity.A) ClCH2COOH B) Cl2CHCOOH

C) Cl3CCOOH D) CH3COOH

1) A > B > C > D 3) C > B > A > D

2) D > C > B > A 4) B > C > A > D

Question: 3.10 True (A) / False (B)

Trichloroacetic acid, Cl3CCOOH, is more acidic than trifluoroacetic acid, F3CCOOH.

• Consider four possible factors (ARIO)* that affect the stabilization of a formal charge.The more effectively a conjugate base can stabilize its formal negative charge the weaker it is as a base. Conceptually, consider that it is done by spreading the negative charge, lowering electron density, and/or by reducing orbital size, which increases electron proximity and attraction to the positive nucleus. These factors make for a weaker base compared to a molecule that cannot affect the charge distribution as well. The corollary is that its parent acid is a stronger acid.

ARIO: The type of Atom that has the formal charge. (A more

electronegative atom is better at stabilizing negative charge.) Resonance (Delocalizing the negative charge makes for a weaker

base.) Induction (“Push-Pull” electronic effects.)

The type of Orbital where the charge resides:

Comparing Acid-Base Strengths

*Professor David Klein, U. of Chicago

Approximate pKa Values of Functional Groups

Professor William Blatchley, Keene State College

Induction

pKa

acetic acid (X = H-) 4.75

butyric acid (X = CH3CH2-) 4.85

chloroacetic acid (X = Cl-) 2.87

4-chlorobutyric acid (X = ClCH2CH2-) 4.52

3-chlorobutyric acid (X = CH3CH2Cl-) 4.05

2-chlorobutyric acid (CH3CH2CHCl-COOH) 2.88

alkyl groups are weakly electron donating

chlorines are electron withdrawing (Note: the proximity of chlorine has an important effect)

Substituent Effects:

“Electron Donating”: Positive effect on pKa, (Weaker Acid) eg. (butyric vs. acetic acid)“Electron Withdrawing”: Negative effect on pKa, (Stronger Acid) eg. chlorine

X-CH2COOH

Using ARIO principles, predict which of the protons in the following structure of acetylsalicylic acid is the most acidic.

Question: 3.11

An Organic Base in ContextErythroxylon spp.

• It is a very valuable plant. The leaves are chewed by indigenous tribes in the Andes to boost their energy.

• It has been used as a psycho-therapeutic, an opthalmic anesthetic and was purportedly used in a popular beverage many years ago that is at the heart of a $20 billion corporation.

• However, both its base and conjugate acid are currently controlled substances under U.S. Federal Regulations: Title 21 secs. 329.1 & 1308.12 (1987).

• Can you name the beverage and the base?

The beverage reportedly produced using the extract of leaves of Erythroxylon coca:

The compound: cocaine, is an organic base: Merck Index,

#2450, 11th ed.: Caution: May be habit forming….

Acid -Base Chemistry(Physical Properties)

• m.p. 98 oC• b.p. (very volatile

> 90 oC)

Solubility: • Water: 1.67 x 10-3

g/mL • CHCl3: 1.43 g/mL

• Ether: 0.29 g/mL What structural feature makes cocaine a base? What simple compound can you relate it to?

“Regular” Cocaine

Conjugate Acid of Cocaine(Physical Properties)

• m.p. >195 oC

Solubility:• Water: 2.5 g/mL • CHCl3: 0.08 g/mL

• Ether: insoluble

What accounts for the differences in solubilities of the base and conjugate acid?

Comparison(Physical Properties)

• m.p. 98 oC• b.p. (very volatile > 90

oC)

Solubility: • Water: 1.67 x 10-3 g/mL • CHCl3: 1.43 g/mL

• Ether: 0.29 g/mL

Crack Cocaine: (Base)

• m.p. >195 oC

Solubility:• Water: 2.5 g/mL • CHCl3: 0.08 g/mL • Ether: insoluble

Regular Cocaine (Conjugate Acid)

http://en.wikipedia.org/wiki/Cocaine

• When bonds break and form, electrons move, and we can show their electron movements with curved arrows.

• Consider the following generic acid/base reaction.

• Each double-headed, curved arrow above shows the movement of two electrons. (A single headed arrow represents a single electron, as in Free Radical Reactions.)

• Viewing all of the curved arrows represents the reaction MECHANISM, which accounts for where the electrons came from, how they moved, and where they wound up.

Curved Arrows in Organic Reactions

Acid -Base Reactions

Acid Base Reactions

QUESTION: 3.12Aniline, C6H5NH2, was isolated in the 1800s and

began immediate use in the dye industry. What is the formula of the species present in a solution of aniline that is at a pH = 2?

A. C6H5NH2+

B. C6H5NH3+

C. C6H5NH–

D. C6H5NH+

E. C6H5NH2

Which form is favored? Acid or Conjugate Base?

• If the pH of the surroundings is < than a compound’s pKa, the compound will exist primarily in its acidic form.

• If the pH of the surroundings is > than a compound’s pKa, the compound will exist primarily in its basic form. • NOTE: Remember that a buffer solution (surroundings)

maintains a nearly constant pH within certain parameters.

€

pH = pKa − logHA[ ]

A−[ ]

Solution effects: The pH of the surroundings (i.e. independent of the acid-conjugate base pH contribution) controls which form is favored, acid or conjugate base, and relates to the following equation.

A weak acid RCO2H, pKa = 5.2

99% acid1% base

90% acid10% base

50% acid50% base

10% acid90% base

1% acid99% base

Aspirin has a pKa of 3.5. In the stomach,

pH ~ 2, what form of aspirin is favored?

QUESTION: 3.13

QUESTIONS from Worksheet:

The pKa of a general anesthetic, sodium pentothal, is 7.4.  If a patient is given sodium pentothal orally instead of iv, will it put the patient to sleep?

What information is needed to answer this fundamental anesthesiology (“gas passer”) question?

A drug has a pKa of 7.8 and is a known teratogen.  If given iv to a pregnant woman whose blood pH is within normal levels, will this drug cross the placenta and affect the baby?

What information is needed to answer this anesthesiology (“gas passer”) question?

Lewis Acids and Bases

• Lewis Acid: electron pair acceptor• Lewis Base: electron pair donor• Example:Al3+ + 6HOHAlOHH63+

Question: 3.14

Select the chemical equation that depicts the correct movement of electrons in the reaction of ammonia with hydrogen chloride.

A) B)

C) D)

Acid-Base ReactionsShowing a reaction with arrows

CH3

SCH3

+ BF3 (CH

3)

2S–BF

3

CH3

+ H2

O

O

CH3

CCH3

+ H3

O

HC ≡ C

+ H2

=C O HC ≡ –C CH2

– O

I

+ CH3

Br ICH3

+ Br

CH3

O

+ CH3

SH CH3

+ OH CH3

S

H2

+ O CH3

CCH3

O H

CH2

=CH2

+ HClCH

2–CH

3 + Cl

C H3

O H2

Worksheet 5: Acids & Baseshttp://chemconnections.org/organic/chem226/226assign-12.html#Worksheets

N

H

OHH+

Base Acid

N

H

OHH+

BaseAcid

CH3

CH3

CH3

CH3

Draw products for the following acid/base reactions, and label the conjugate products.

Acid-Base ReactionsPredicting Products

O

C H3

C

O H

+ HCO3

O

C H3

C

O H

+ AlCl3

B(CH3

)3

+ (CH3

)3

N

+

OH

C O

H3

C

H3

C

+ MgCl2

H2

SO4

+ CH3

OCH3

BF3

+

O

N H3

Worksheet 5: Acids & Baseshttp://chemconnections.org/organic/chem226/226assign-12.html#Worksheets

Predicting if reactions occur and the products if they do

a. HO + Br–CH3 HO–Br + CH

3

HO–CH3

+ Br

b. H–C ≡ + C H2

=C O H – C ≡ C – C H2

- O

H – C ≡ C – O – C H2

NH2

+ –H OCH3

H2

–N OCH3

+ H

H2

– + N H OCH3

+ –HO Br CH3

,c

–H C ≡ + C H2

=C O

NH2

+ –H OCH3

Worksheet 5: Acids & Baseshttp://chemconnections.org/organic/chem226/226assign-12.html#Worksheets

Using pKa values given in the structure below, what is the product of the

following reaction (NH4+/NH3, pKa = 9.3/ pKb = 4.7)?

Consider that the reaction is with 1 mole of each reactant.

A.

B.

C.

D.

Question: 3.15

• A large amount of solvent, which surrounds a substrate, can profoundly affect the substrate’s properties.

• Consider the following solvent and ion–dipole attractions of two different bases, which are both stabilized by the interactions.

• The tert-butoxide ion is sterically hindered, and is not as well solvated

as the ethoxide ion.

“Solvation”: Solvent Effects

QUESTION: 3.16 Which has a lower pKa in water?A) tert-butanol or B) ethanol

An appropriate SOLVENT for an acid/base reaction: Should be able to surround the reactants and facilitate their

collisions, increasing the rate of reaction. Should NOT itself react with the reactants.

Because water can act as an acid or a base, it has a LEVELING EFFECT on strong acids and bases, which are common reactants or intermediates in many organic reactions:

Acids stronger than H3O+ cannot be used in water.

Bases stronger than OH- cannot be used in water.

Choosing a Reaction Solvent

Water would not be an appropriate solvent for the following reaction. WHY?

N+

H

HN+

NaNH2 + H2O → NH3 + NaOH

Which of the following solvents would be the best choice to use in the reaction:

Question: 3.17

O

OHor or

N+

H

HN+

A) CH3COOH B) C) D)