AMINES Dr. Sheppard CHEM 2412 Summer 2015 Klein (2 nd ed.) sections: 23.1, 23.2, 23.3, 23.13, 23.4, 23.5, 23.6, 23.8

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. -NH 2 as a substituent is “amino” Order of precedence of functions

I. Nomenclature (Review) Common name system for amines Name alkyl group(s) List in alphabetical order Add “amine” Examples: StructureName CH 3 CH 2 NHCH 3 (CH 3 CH 2 ) 2 NH

I. Nomenclature (Review) Aromatic amines StructureName

I. Nomenclature (Review) Pyridine If substituted, nitrogen is atom 1 of the ring. Number in direction of other substituents.

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

II. Structure Geometry Hybridization of N? Electron arrangement = tetrahedral Shape = pyramidal Bond angle around N?

II. Structure Amines can be chiral Not easily separated from enantiomer (unless 4° ammonium salt) Nitrogen inversion (pyramidal inversion)

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

13 C-NMR: Atoms bonded to N are deshielded 1 H-NMR: N-H signal shifts around from  N-H signal is usually broad and shows no splitting Hydrogens on carbons adjacent to N at  2-3 III. Spectroscopy of Amines: NMR

1 H-NMR spectrum for 2-ethylaniline 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  -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. H 2 O) Solubility in water Low MW amines are soluble in water Solubility decreases as MW increases Salts of amines are more soluble than neutral amines IV. Physical Properties of Amines

Boiling points Higher than hydrocarbons; lower than alcohols (why?) Tertiary amines lower than primary or secondary Quaternary salts = ionic = very high MP and BP IV. Physical Properties of Amines

Odor Low MW amines = fishy Higher MW amines: IV. Physical Properties of Amines

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 amines are better solvated, but those of tertiary amines are more stable through induction Primary, secondary and tertiary amines are all stronger bases than ammonia Note pK a values for conjugate acid Lower pK a 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) Stabilized by resonance Also loses its aromaticity when protonated (Chapter 18 later this semester), so less basic

V. Basicity of Amines sp-hybridized N’s are less basic than sp 2 -hybridized N’s, which are less basic than sp 3 -hybridized N’s More s-character holds electrons more tightly Electrons are less available/less basic Note pK b values for amine Lower pK b indicates stronger base

VI. Preparation of Amines 1. Reduction of nitriles 2. Reduction of amides

VI. Preparation of Amines 3. Reduction of aromatic nitro groups

VI. Preparation of Amines 4. S N 2 reactions with alkyl halides Often yields multiple substitution products Products can continue to act as nucleophiles

VI. Preparation of Amines 5. Reductive amination (review)

VII. Reactions of Amines 1. Alkylation (S N 2 with alkyl halide) 2. Formation of imine (as in reductive amination) 3. Nucleophilic acyl substitution Product = amide Will see with carboxylic acid derivatives (Chapter 21)