Organic Chemistry

886 CHAPTER 21 More About Amines • Heterocyclic Compounds

The lone pair is required for inversion: Quaternary ammonium ions—ions with four

bonds to nitrogen and hence no lone pair—do not invert.

Notice that amine inversion takes place through a transition state in which the

nitrogen becomes an nitrogen. The three groups bonded to the nitrogen are

coplanar in the transition state with bond angles of 120°, and the lone pair is in a por-

bital. The “inverted”and “non-inverted”amine molecules are enantiomers, but they

cannot be separated because amine inversion is rapid. The energy required for amine

inversion is approximately (or ), about twice the amount of ener-

gy required for rotation about a carbon–carbon single bond, but still low enough to

allow the enantiomers to interconvert rapidly at room temperature.

21.3 More About the Acid–Base Properties of Amines

Amines are the most common organic bases. We have seen that ammonium ions have

values of about 11 (Section 1.17) and that anilinium ions have values of about

5 (Sections 7.10 and 16.5). The greater acidity of anilinium ions compared with am-

monium ions is due to the greater stability of their conjugate bases as a result of elec-

tron delocalization. Amines have very high values. For example, the of

methylamine is 40.

Saturated heterocycles containing five or more atoms have physical and chemical

properties typical of acyclic compounds that contain the same heteroatom. For exam-

ple, pyrrolidine, piperidine, and morpholine are typical secondary amines, and

N-methylpyrrolidine and quinuclidine are typical tertiary amines. The conjugate acids

of these amines have values expected for ammonium ions. We have seen that the

basicity of amines allows them to be easily separated from other organic compounds

(Chapter 1, Problems 70 and 71).

PROBLEM 2

Why is the of the conjugate acid of morpholine significantly lower than the of the

conjugate acid of piperidine?

pKa pKa

pKa

pKa pKa

pKa pKa

6 kcal>mol 25 kJ>mol

sp^2 sp^2

sp^3

R^2

R^1 N

transition state

amine inversion

R^3

N

R^2

R^3

R^1

N

R^2

R^1 R^3

sp^3

sp^3 sp^2

p orbital

‡

3-D Molecules:

Aziridinium ion; Pyrrolidine;

Piperidine; Morpholine

pKa = 10.8

CH 3 CH 2 CH 2 NH 3

+

pKa = 40

CH 3 NH 2

pKa = 10.9

CH 3

CH 3 NH 2

+

pKa = 11.1

CH 2 CH 3

CH 2 CH 3

CH 3 CH 2 NH

+

pKa = 4.58

+

NH 3

pKa = 5.07

CH 3

+

NH 3

N

HH

NN N

O

N

pyrrolidine

pKa = 11.27

the ammonium ions of: piperidine

pKa = 11.12

morpholine

pKa = 9.28

N-methylpyrrolidine

pKa = 10.32

quinuclidine

pKa = 11.38

HH HH H

H

CH 3

+++ +

+