AMINES

Dr. Sheppard

CHEM 2412

Fall 2014

McMurry (8th ed.) sections: 24.2, 24.3, 24.4, 24.6, 24.7,

24.9, 24.10

Amines• Derivatives of ammonia• Neurotransmitters• Medicines• Amino acids, nucleic acids

Amines

I. Nomenclature Review

II. Structure

III. Spectroscopy

IV. Physical Properties

V. Basicity

VI. Preparation

VII. Reactions

I. Nomenclature (Review)

1. Parent chain is longest containing C bonded to –N

2. Change suffix “-e” to “-amine”

3. Number from end closest to –N. Show location of –N.

4. Name/number substituents

5. -NH2 as a substituent is “amino”• Order of precedence of functions

NH2

2-butanamine

CH3 CH2 CH2 CH2 CH CH3

N

CH3 CH3

NH2

2-methyl-1-pentanamine

HO NH2

I. Nomenclature (Review)

• Common name system for amines• Name alkyl group(s)• List in alphabetical order• Add “amine”

• Examples:

Structure Name

CH3CH2NHCH3

(CH3CH2)2NH

I. Nomenclature (Review)• Aromatic amines

Structure Name

NH2

NH2

CH3

NH

CH3

I. Nomenclature (Review)• Pyridine

• If substituted, nitrogen is atom 1 of the ring. Number in direction of other substituents.

N

N

CH3

3-methylpyridine

II. Structure• Classification as 1°, 2°, 3°, 4°

II. Structure• Geometry

• Hybridization of N?• Electron arrangement = tetrahedral• Shape = pyramidal• Bond angle around N?

• Amines can be chiral• Not easily separated form enantiomer (unless 4° ammonium salt)• Nitrogen inversion (pyramidal inversion)

III. Spectroscopy of Amines: IR• Absorption(s) at 3300-3500 cm-1 for N-H

• 13C-NMR: • Atoms bonded to N are deshielded

• 1H-NMR: • N-H signal shifts around from d2-5• N-H signal is usually broad and shows no splitting • Hydrogens on carbons adjacent to N at d2.2-2.6

III. Spectroscopy of Amines: NMR

III. Spectroscopy of Amines: MS• Nitrogen rule: if a molecule has an odd number of nitrogen

atoms, the mass will be an odd number• Odd masses have 1 or 3 nitrogen atoms• Even masses have 0 or 2 nitrogen atoms

• Molecule fragments by carbon bonded to amine• a-cleavage

III. Spectroscopy of Amines: MS• Ex: ethylpropylamine

• Amines are strongly polar• Primary and secondary amines form H-bonds (neat)

• Tertiary amines only accept H-bonds from donor (e.g. H2O)

• Boiling points • Higher than hydrocarbons; lower than alcohols (why?)• Tertiary amines lower than primary or secondary• Quaternary salts = ionic = very high MP and BP

• Solubility• Low MW soluble in water; decreases as MW increases• Salts of amines are more soluble in water than neutral amines

IV. Physical Properties of Amines

• Odor• Low MW amines = fishy• Higher MW amines:

IV. Physical Properties of Amines

H2N NH2

cadaverine

H2N

NH2

putrescine

V. Basicity of Amines• Amines have lone pair on N

• More basic than alcohols (more stable conjugate acid)• More basic than amides (amides stabilized by resonance)

V. Basicity of Amines• Trends in basicity

• Tertiary, secondary, and primary amines are all approximately equal in basicity• Conjugated acids of

primary are better solvated, but those of tertiary amines are more stable through induction

• Primary, secondary and tertiary amines are all stronger bases than ammonia

R N H

H

H

R N H

R

R

Note pKa values for conjugate acidLower pKa indicates weaker base

V. Basicity of Amines• Aromatic amines are weaker

bases than aliphatic amines• Aniline

• Stabilized by resonance• Less basic/nucleophilic

• Pyrrole (a heterocycle)• Loses its aromaticity when protonated

(Chapter 15 later this semester),

so less basic

N

H

N

H

V. Basicity of Amines• sp-hybridized N’s are less basic than sp2-hybridized N’s,

which are less basic than sp3-hybridized N’s• More s-character holds electrons more tightly• Electrons are less available/less basic

CH3 C N

pKb = 24N

pKb = 8.75

N

H

pKb = 2.88

Note pKb values for amineLower pKb indicates stronger base

VI. Preparation of Amines

1. SN2 reactions with alkyl halides

• Often yields multiple substitution products • Products can continue to act as nucleophiles

VI. Preparation of Amines

2. Reduction of nitriles

3. Reduction of amides

VI. Preparation of Amines

4. Reduction of aromatic nitro groups

VI. Preparation of Amines

5. Reductive amination

VII. Reactions of Amines

1. Alkylation (SN2 with alkyl halide)

2. Formation of imine (as in reductive amination)

3. Nucleophilic acyl substitution• Product = amide• Will see in carboxylic acid derivative chapter