Acidity and basicity of organic compounds:

(1)

Development of Complex Curricula for Molecular Bionics and Infobionics Programs within a consortial* framework**

Consortium leader

PETER PAZMANY CATHOLIC UNIVERSITY

Consortium members

SEMMELWEIS UNIVERSITY, DIALOG CAMPUS PUBLISHER

The Project has been realised with the support of the European Union and has been co-financed by the European Social Fund ***

**Molekuláris bionika és Infobionika Szakok tananyagának komplex fejlesztése konzorciumi keretben

***A projekt az Európai Unió támogatásával, az Európai Szociális Alap társfinanszírozásával valósul meg.

PETER PAZMANY CATHOLIC UNIVERSITY SEMMELWEIS

UNIVERSITY

(2)

Organic and Biochemistry

Acidity and basicity of organic compounds:

donating and accepting proton and beyond

(Szerves és Biokémia )

(Szerves vegyületek aciditása, bázicitása: protont adni és kapni, s ezen túl)

semmelweis-egyetem.hu

Compiled by dr. Péter Mátyus

with contribution by dr. Gábor Krajsovszky

Formatted by dr.Balázs Balogh

(3)

Acid-base theory I.

(summary)

- Brøensted theory:

acid: proton donor base: proton acceptor every acid has a conjugate base every base has a conjugate acid

- Lewis theory (1916)

acid: electron pair acceptor base: electron pair donor

A H

+

^B ^A

+

^{B H}

acid₁ base₂ base₁ acid₂

+

B A B A

BH₃

+

^(CH³⁾²^N

+

^N(H³^C)³ ^BF³

(5)

Acid-base theory II. (summary)

Thermodynamical parameters:

concentration of water ~ is constant

[ ][ ]

[ ^H ^H Ô Ô ][ ] ^HA Â

K

2

- eq 3

=

+ (complete equilibrium constant)

+ ^HA + ^A

^-

O

H

₂

H

₃

O

⁺

(pseudo equilibrium constant) characterization of acidic strength

[ ][ ]

[ ] ^HA ^A

K H

- a

=

+

K_a = K_eq [H₂O] pK_a = - log K_a if: K_eq = 1 K_a = [H₂O] = 55.56 pK_a = - log [H₂O] = - 1.745

(6)

Acid-base theory III. (summary)

Weak acids:

Strong acids:

K_eq << 1, K_a << [H₂O]

pK_a >> - log [H₂O]

pK_a >> - 1.75

e.g., CH₃COOH pK_a 4.76 CH₃CH₂OH pK_a 16 K_eq << 1, K_a >> [H₂O]

pK_a << - log [H₂O]

pK_a << - 1.75

e.g., HCl pK_a -7

Cl CCOOH pK 16

(7)

R C O O

H Na O H R C O

O

Na H O H

Stronger acid pK_a = 3-5

Stronger base Weaker base Weaker acid pK_a = 15.7

C O

O H Na O H C O

O

H O H Na

Insoluble in water Soluble in water

R NH₂ H O H H

Cl R N H

H H

Cl O H

H Stronger base Stronger acid

pK_a= 1.74

Weaker acid pK_a = 9-10

Weaker base

(8)

(CH₃)₃CO H H tert-butyl (CH₃)₃CO H₂ alcohol

Stronger acid pK_a = 18

Stronger base (from NaH)

Weaker base Weaker acid pK_a = 35 CH₃CH₂O H H ethyl alcohol CH₃CH₂O H₂ Stronger acid

pK_a = 16

Stronger base (from NaH)

Weaker base Weaker acid pK_a = 35

R C C H NH₂

Stronger base (from NaNH₂)

liquid

NH₃ R C C NH₃

H C C H NH₂

Stronger base (from NaNH₂)

liquid

NH₃ H C C NH₃

H O H NH₂ H O NH₃

Stronger acid pK_a = 15.7

Stronger base Weaker base Weaker acid pK_a = 38

(9)

Acid-base theory IV. (summary)

Trends:

Acidity

1. C-H < N-H < O-H < F-H

electronegativity 2. HF < HCl < HBr < Hi

3. ClCH₂COOH < Cl₂CHCOOH

inductive effect 4. ClCH₂COOH < FCH₂COOH

5. R-CH₂OH < R-COOH resonance effect 6. sp³ < sp² < sp hybridisation

Organic compounds

RH < ROH < RSH < ArOH < ArSH < RCOOH < RSO₂OH

(10)

Acid-base theory V. (summary)

Basic strength

pK_a also defines the strength of the conjugate base of an acid.

The higher the pK_a value of the conjugate acid is, the stronger the base is.

Malodinitrile is a stronger acid, than methanol;

methoxide anion is a stronger base, than the conjugated basis of malodinitrile

H⁺

+

N C CH₂ C N N C CH₂ C N

H⁺

+

C

H₃ O^- C

H₃ OH

pK_a ≈ 11

pK_a ~ 15

(11)

An acid A reacts with any base, the conjugate acid of which is weaker than the acid A.

Acid-base theory VI. (summary)

E.g.,

+ ^{N C} ^CH

²

^{C N}

N C CH

₂

C N

+

C

H

₃

O

^-

C

H

₃

OH

(12)

Acid-base theory VII. (summary)

Extreme values (records)

- Superacids (Prof. George Oláh) Brønsted + Lewis acids

H₀ scale for pH-s < 0 [-H₀]

HF + SbF₅ -H₀ ~ 20-30 - The weakest acids: R-H (alkanes)

E.g.,

H⁺

+

C

H₃ CH₂^- CH₂ H

C H₃

(13)

Proton sponges

2

bis(dimethylamino)-fluorene a very strong base

Unfavorable interaction between the non-bonding electron pairs of the nitrogens is relieved on protonation.

Protonation: the disadvantageous interaction is relieved, and moreover, there is a stabilising H-bond.

Results

3

N,N-dimethylaniline

pK_a (conj. acid): 2 >10 3 = ca. 5

2

N C H₃

C H₃

N

CH₃ CH₃

N₊ C H₃

C H₃

N

CH₃ CH₃

H N

C

H₃ CH₃

(14)

1. Mark electronic effect of the heteroatom in the following compounds.

Explain A/ acidity B/ basicity of these compounds according to the electronic effects.

H₃C CH₂ CH₂ OH H₃C CH CH OH

A/

a) b)

a) H₃C CH₂ CH₂ NH₂ H₃C CH CH NH₂ b)

B/

(15)

2. Make increasing acidity order of the following compounds (in aqueous solutions):

(16)

3. Make increasing basicity order of the following compounds (in aqueous solutions):

CH

₃

CH

₂

NH

₂

NH H

₃

C

H

₃

C

N H

₃

C H

₃

C H

₃

C

I. II. III. IV.

N CH

₃

CH

₃

H

₃

C CH

₃

HO

(17)

4. Suggest reaction conditions for the following reactions:

A/ alkylation of malononitrile by methyl iodide;

B/ preparation of sodium methanolate from methanol.

A/

B/

N C CH

₂

C N alkilezés

I. CH

₃

OH II.

alkylation

Acidity and basicity of organic compounds:

Organic and Biochemistry

Acidity and basicity of organic compounds:

donating and accepting proton and beyond

Compiled by dr. Péter Mátyus

with contribution by dr. Gábor Krajsovszky

Formatted by dr.Balázs Balogh

Table of Contents

Acid-base theory I.

(summary)

+

+

+

+

+

Acid-base theory II. (summary)

[ ][ ]

[ H H O O ][ ] HA A

K

=

+ HA + A

O

H

H

O

[ ][ ]

[ ] HA A

K H

=

Acid-base theory III. (summary)

Acid-base theory IV. (summary)

Acid-base theory V. (summary)

+

+

Acid-base theory VI. (summary)

+ N C CH

C N

N C CH

C N

+

C

H

O

C

H

OH

Acid-base theory VII. (summary)

E.g.,

+

Proton sponges

CH

CH

NH

NH H

C

H

C

N H

C H

C H

C

I. II. III. IV.

N CH

CH

H

C CH

HO

A/

B/

N C CH

C N alkilezés

I.

CH

OH II.

[ ^H ^H Ô Ô ][ ] ^HA Â

+ ^HA + ^A

[ ] ^HA ^A

+ ^{N C} ^CH

^{C N}