ACID and BASES - a Summary

Stefan Svensson 2004

ACID and BASES - a Summary

Brönsted-Lowry : Acids donate protons Bases accept protons

Lewis -acid : Electron pair acceptor Lewis-base: Electron pair donator.

+ H₃O C

O O CH₃

C O

OH

CH₃ + H₂O

Acetic acid ättiksyra

Aniline _NH2 + H₂O _NH3 + OH

[CH₃COOH][H₂O]

K_eq = [H₃O⁺] [CH₃COO^-] Acidity constant Ka:

K_a = K_eq [H₂O] = [H₃O⁺] [CH₃COO^-]

[CH₃COOH] = 1,76 x 10^-5 pK_a = -log K_a =4,76 Ju starkare syra - ju svagare korresponderande bas.

Basstyrkan kan relateras till pKa för dess korresponderande syra.

Ju större pKa värde för korresponderande syra- ju starkare är basen.

Relative strength for some acids and their conjugate bases,

ACID pKa Conj. BASE

Strongest acid HSbF₆ > -12 SbF_6- Weakest base

HCl - 7 Cl-

CH₃COOH 4.8 CH₃COO-

CH₃NH₃+ 10 CH₃NH₂

H₂O 15,7 OH-

(CH₃₎₃COH 18 (CH₃₎₃CO-

NH₃ 33 NH_2-

Weakest acid CH₃CH₃ 50 CH₃CH_2- Strongest base

Ex Lewis acids: BF₃ AlCl₃ TiCl₄ ZnCl₂

HCl, HNO_3, HClO₄ are complete ionised in water and appears to have the same strength (the leveling effect of water)

Factors that influence the acidity of an organic compound H-A

A • The strength of the H-A bond B • The electronegativity of A

C • Factors stabilising A- compared with H-A D • The nature of the solvent

pKa ≈ 16

pKa ≈ 43 CH₃ O H

CH₃ H

OH pKa ≈ 10 RCOOH ^{pKa ≈ 4-5}

Examples

A- Bonding strength to the proton

H-F < H-Cl < H-Br < H-I Increased acidity ⇔

pKa: ^{3,2 -7 -9 -10} decreased bonding strength

F - > Cl - > Br - > I - Increased Basicity H₂O < H₂S < H₂Se Higher acidity OH - > SH - > SeH - Increased Basicity B- Acidity increase with electronegativity

CH₄ < NH₃ < R-OH < HF

Electronegativity affect both polarity and the stability of the anion.

Acidity increase with increased s-character in the hybridisation

CH3-CH3 < _H2C=CH2 < HC≡CH Increased acidity sp3 sp2 sp

pKa: ≈ 50 44 25

Increased s-character binds the electrons closer to the carbon nucleus More s-contribution ⇒ lower energy and higher anion stability

Ex.

pK_a = 33 pK_a = 25

+ NH₃

C C

CH₃ NH₃

+ NH₂

C C

CH₃ H

C Lower pKa for Carboxylic acids than Phenols due to:

Resonance structures of the anion have identical energy The anion contain two electronegative oxygen atoms

pKa ≈ 3,8

H C

O O

H C

O O

H C

O OH

Phenol:

O O

O O O

OH

pKa ≈ 10

The negative charge is spread by electron- withdrawing and thereby stabilising the anion C

CH₂

Cl O

O pK_a

C O CH₂ OH Cl

CH₃CH₂OH C

O OH CH₃

2,9 15,9 4,8

D. Polar solvent with high dielectric constant (ε) have better ability to solvate ions Water is extremely effective as ion solvating medium and is readily polarised, and can thereby stabilise and solvate both cations and anions

The solvent must act as a base otherwise can not acids dissociate.

Ex. HCl is a strong acid in methanol but not in toluene.

ACIDS

Aliphatic acids

Alkyl groups can inductively decrease the acid strength

Compare: acetic acid and formic acid pKa 4,76 versus 3,77

O C

O H

O C

O Me

But often depends differences in relative solvation possibilities of ionisation.

∆Go = -2.303 RT log Keq

∆Go = ∆Ho - Τ∆So and

pKa ∆Go ∆Ho Τ∆So

4,76 6,5 -0,13 - 6,6 Kcal 3,77 5,1 -0,07 - 5,17 Kcal Acetic acid

Formic acid

Low enthalpy The energy required for dissociation of the O-H bond is canceled by the energy evolved in solvating the resultant ions.

Entropy has a greater effect Through solvation of the ions by water molecules is the orderliness increased. Differential solvation of the acid anions makes the acid strength to differ. Formiat ion is stronger solvated.

For other short aliphatic acid (C3-C5) are the differences in pKa small, Minor steric effects may count for the differences (pKa ≈ 4.80 - 5,05)

Hybridisation

Stronger acid pKa

4,88 sp3 4,25 sp2 1,88 sp

HC C COOH

CH₂ CH COOH CH₃ CH₂ COOH

Electrons are drawn closer to unsaturated carbon nucleus - larger s contribution This change the inductive effect from donating to withdrawing when sp3 → sp.

Similar to acidities in the serie: ethane - ethene- ethyne

Substituted aliphatic acids

CH₃ C OH O

CH₂ C OH O

F CH₂ C OH

O

Cl CH₂ C OH

O

Br CH₂ C OH

O I

4,76 2,57 2,86 2,90 3,16

C OH CH

O Cl

Cl C C OH

O Cl Cl

Cl C OH

CH₂ O Cl

2,86 1,25 0,65

Inductive effects ( electron withdrawing, EW) delocalise the negative charge over the whole of the anion. The water can be less ordered to solvate the ions.

The changes in pKa and then free energy is largely due to entropy factor also here.

Entalphy differ only little with different substituent.

The anionic charge gets more concentrated as the EW-substituent is situated further apart ⇒ increased ∆S

Phenols

The Inductive effect falls off with distance from orto > meta > para, but is also combined with mesomeric effect which affect primary at orto- and para-positions.

pKa 9,95 7,23 8,35 7.14 4,01 1,02 C₆H₅OH

o-O₂NC₆H₄OH m-O₂NC₆H₄OH p-O₂NC₆H₄OH 2,4-(O₂N)₂C₆H₄OH 2,4,6-(O₂N)₃C₆H₄OH

O

N

O O

O

N

O O

With more powerful EW groups the negative charge gets delocalised

⇒ decreased ∆S (solvation can be less ordered) ⇒ lower pKa.

C₆H₅OH o-MeC₆H₄OH m-MeC₆H₄OH p-MeC₆H₄OH

pKa 9,95 10,28 10,08 10.19 Methyl

Alkyl groups have only marginal effects.

Aromatic carboxylic acid

Benzoic acid pKa 4,20 is stronger than the saturated acid ( 4,87).

Phenyl as double bond is less electron donating than saturated acids.

pKa of X-C⁶H₄COOH

H Me NO₂ Cl Br OMe OH 4,20 - 2,17 2,94 2,85 4,09 2,98 4,20 4,24 3,45 3,83 3,81 4,09 4,08 4,20 4,34 3,43 3,99 4,00 4,47 4,58

C

N

O O

O O

C

X O O C

X O O

EW-groups increases the acid strength, mesomeric effect may also decrease strength.

HO and MeO- groups may have both inductive (EW) and mesomer effect (ED) depending on position. The effect can give a weaker acid also.

O C O

O H H

O

C O O - H⁺ H

Orto groups may also besides short inductive distance act through space, or as few cases with intra-molecular hydrogen bonding

Again is the ∆S term most important for the pKa value.

Dicarboxylic acids

HOOC-COOH HOOC-CH₂-COOH HOOC-CH₂-CH₂-COOH

pKa 1,23 2,83 4,19 The inductive EW- effect of the second

COOH falls off sharply as the COOH-groups are separated more than one saturated carbon.

Maleic acid has a low pK_a1 compared with fumaric acid due to intra molecular H- bonding, which on the other hand also makes pKa2 higher due to stabilisation.

C C C

C H

O

O O

O

H H H

C C

COOH

HOOC H H

C C C

C H

O

O O O

H H

-H^-

pK_a1= 1,92 pKa2= 6,23 pK_a1= 3,02 pKa2= 4,38 Maleic acid

Fumaric acid

For malic and succinic acid is pK_a2 higher as the first COO- group is Elect. Donating.

As the entropy has a major effect on pKa:s also temperature influences the value of pKa.

BASES

9,25 pKa

The smaller value of pKa for BH⁺ the weaker B is as a base

∆Go ∆Ho Τ∆So

12,6 12,4 0,2 Kcal

Ka = [B] [ H₃O⁺ ] [ BH⁺ ] More convenient to use pKa also for bases

NH₄⁺ +H₂O NH₃ + H₃O⁺

Enthalpy changes are more important than entropy changes.

∆S is low as both sides has the same kind of ions, equally solvated.

Aliphatic bases

NH₃ ^{Me NH}

Me NH₂ Me Me N

Me

Me Et

Et NH

Et NH₂ Et N

Et Et

pKa: 9,25 10,64 10,77 9,80 10,67 10,93 10 88 Alkyl groups on ammonia increases the base strengthThe first one markedly, the second slightly but the third actually decrease base strength.

Not only electron availability on the nitrogen also solvation of the cation must be stabilised. Tertiary amines less easily solvated.

The more hydrogen atoms attached on nitrogen the more powerful solvation via H- bonding between these and water.

N H

H

R H N

H

H R

R N

H

R R R

O₂H H₂O

H₂O

H₂O

H₂O

H₂O

> >

Decreasing stabilisation by solvation

Increasing electron-donating inductive effect on basicity

In solvent where ions are not solvated by H-bonding is the order of base strength the same as the inductive effect of the alkyl groups.

In chlorobensen or gas phase: But NH2 < But2NH < But 3N

EW inductive groups reduce the base strength: Cl, NO2 CF3

F₃C N F₃C F₃C

R C O

NH₂ R C

O

NH₂

C N C

O

O

H acidic H Amide nitrogens are non basis due to mesomeric EW effect (pKa ≈ 0,5).

Pthalimide, with two carbonyls , is acidic and non-basic.

R4N+ OH- as a ion pair has a base strength alike alkali bases

Guanidine has pKa of ≈ 13,6 and protonation gives three exactly equal resonance structures.

Anilines

NH₂ NH₂ NH₂ NH₂ NH₂ H NH₂

H

+

pKa ≈ 4,6 (Compare with cyclohexylamine pKa 10,7)

Unshared electrons on N can interact with the delocalised π-electrons in the ring.

In protonated form is this stabilisation not available.

Ph₂NH pka ≈ 0,8 and Ph3N is not basic at all.

_o-Me-C

6H₄NH₂ m-Me-C₆H₄NH₂ p-Me-C₆H₄NH₂ pKa

4,62 4,38 4,84 4,67 5,15 5,10 C₆H₅NH₂

C₆H₅NHMe C₆H₅NMe₂ Alkyl groups

Alkyl groups do only effect little whatever position, and the main effect on the base strength is the mesomeric stabilisation of the aniline molecule with respect to the cation.

Ex Nitro- hydroxy- and methoxy- substituted anilines.

C₆H₅NH₂

o- - 0,28 m- 2,45 p- 0,98

OMe NH₂

OMe NH₂

MeO-C₆H₄NH₂ HO-C₆H₄NH₂

O₂N-C₆H₄NH₂

4,62 o- 4,72

m- 4,17 p- 5,30

o- 4,49 m- 4,20 p- 5,29 NH₂

N

O O

NH₂

O O

N

Orto position gives greatest effect due to strongest inductive effect but also by direct interaction by steric and H-bonding.

Stronger base

N

O O

N N N

O O

O O

CH₃ CH₃

N

O O

N N N

O O

O O

H H

2,4,6-trinitro-N,N-dimethyl aniline is much more stronger base than N,N-dimethyl- aniline or 2,4,6-trinitro-aniline, because the orto groups inhibit resonance

interaction by steric reason.

Hetrocyclic bases

Pyridine (A) aromatic (sp²) pKa 5,2 less basic than ex. triethylamine (sp³) As nitrogen becomes more multiply bonded its lone pair of electrons is

accommodated in an orbital with more s character., the electron are drawn closer to the nitrogen nucleus. Compare also MeCN pKa ≈ -4,3 (sp).

N N

H

N H

H H

N H

H⁺

N N

N R₃N > > RC

N

N

Base strength Hybridisation

(A) (B) (C)

Pyrrole (B) have aromatic character, the electron pair is incorporated in the aromatic 6 π-system, which gives a weaker base. α-Carbons is more basic.

Pyrrolidine (C) on the other hand have pKa ≈11,3 resembling of diethylamine.