Amines The organic bases

Categorizing Amines Amines are categorized by the number of alkyl groups attached to nitrogen : 1º (primary amine)RNH 2 2º (secondary amine) R 2 NH 3º (tertiary amine) R 3 N 4º (quaternary amine salt)R 4 N +

Naming simple amines Simple 1º amines are named as “alkylamine”  Examples: methylamine CH 3 NH 2 ethylamine CH 3 CH 2 NH 2 butylamine CH 3 CH 2 CH 2 CH 2 NH 2 Symmetrical 2º or 3º amines are named as “dialkylamine” or “trialkyamine ”  Examples : diethylamine (CH 3 CH 2 ) 2 NH; trimethylamine (CH 3 ) 3 N

Naming more complex amines Amines with more than one type of alkyl group may be named as N-substituted primary amines. The longer alkyl chain determines the base name.  Examples N-methylpropylamine CH 3 NHCH 2 CH 2 CH 3 N,N-dimethylethylamine (CH 3 ) 2 NCH 2 CH 3

Naming more complex amines Amines that have more than one functional group may be named using “amino” as a substituent on the parent molecule.  Examples: 2-aminoethanol H 2 NCH 2 CH 2 OH 4-aminobutanoic acid H 2 NCH 2 CH 2 CH 2 CO 2 H

Heterocyclic amines Some amines have a nitrogen as part of a ring. These generally have common (non-systematic) names, which should be memorized: anilinepyridinepyrimidine pyrrole quinolineindole imidazolebenzimidazole

Structure of amines Amines have an sp 3 hybridized nitrogen In principle, tertiary amines with three different R groups should be chiral (i.e., have a stereocenter). However, rapid pyramidal inversion of the amine nitrogen prevents isolation of the enantiomers except where the nitrogen is part of a ring or has other geometrical constraint. fast

Properties of amines Amines are moderately polar and are capable of hydrogen bonding. Low MW amines (up to about C 5 ) are soluble in water; higher MW amines will dissolve in acidic solution (as their conjugate acid). Many amines have foul odors. Amines are weak bases.

Example of biologically active amines

More biologically active amines…

Basicity of amines Amines are slightly basic. This because they have a lone pair of electrons to donate to a proton. This same feature makes them nucleophiles. Typical amines have K b values = to 10 -4

Basicity of amines… However, instead of measuring an amine’s basicity using the above equilibrium, chemists usually refer to the acidity of the conjugate acid of the amine. The weaker the conjugate acid, the stronger the base strength of the amine. Typical amines have K a values (of their conjugate acids) of to (pK a values of 10 to 11.)

pK a values of conjugate acids of amines CH 3 NH CH 3 CH 2 NH (CH 3 ) 2 NH10.7 (CH 3 CH 2 ) 2 NH10.5 (CH 3 ) 3 N 9.8 (CH 3 CH 2 ) 3 N11.0 All are about the same value. The same substituent effects that stabilize carbocations that are more highly substituted by alkyl groups are offset by diminished stabilization by solvent due to crowding.

Some amines that are weaker bases (conj. acid) Aniline is a weaker base because the lp of electrons is delocalized by resonance into the aromatic ring. Pyridine is weaker because it is an imine (C=N). Pyrrole is much weaker because the lp of electrons is delocalized with the other  electrons to make 6  e-. Therefore, the lp is unavailable to act as a base. aniline pyridine pyrrole pK a =

Substituent Effects on Basicity of Aniline Resonance stabilizes free base, destabilizes its protonated form (see next slide) 2 explanations of weaker basicity of nitroaniline:

Substituent Effects on Basicity of Anilines

An amine that is a stronger base There is one type of amine that is a stronger base: Guanidine is a strong base because its conjugate acid is stabilized by resonance: guanidine pK a = 13.6 (conj. acid) A guanidine group is part of the structure of the amino acid arginine.

Amines are Protonated at Physiological pH Recall the Henderson-Hasselbalch equation: Consider the neurotransmitter dopamine, a typical amine (having a pK a of its conjugate acid = 10.6) in a living cell (buffered at pH = 7.3): That is, the concentration of the protonated amine is 2000x that of the neutral amine! Typical amines are >99.9% protonated at physiological pH.