Chapter 20 Amines

_Nomenclature

_{Primary amines are named in systematic (IUPAC) nomenclature by} replacing the -e of the corresponding parent alkane with -amine

_{In common nomenclature they are named as alkylamines}

_{Simple secondary and tertiary amines are named in common Simple secondary and tertiary amines are named in common}

nomenclature by designating the organic groups separately in front of the word amine

_{In IUPAC nomenclature the substitutent -NH2 is called the amino} group

Chapter 20 3

_{Aryl Amines}

_{Heterocyclic Amines}

_{The important heterocylcic amines have common names}

_{In IUPAC nomenclature the prefixes aza-, diaza- and triaza- are} used to indicate that nitrogen has replaced carbon in the

corresponding hydrocarbon

_{The nitrogen is assigned position 1 and the ring is numbered to give the lowest}

_{Physical Properties and Structure of Amines}

_{Primary and secondary amines can form hydrogen bonds to each}

Chapter 20 5

_{Primary and secondary amines can form hydrogen bonds to each} other and water

_{Tertiary amines cannot form hydrogen bonds to each other but} can form hydrogen bonds to hydrogen bond donors such as water _{Tertiary amines have lower boiling points than primary or}

secondary amines of comparable molecular weights

_{Structure of Amines}

_{The nitrogen atom in an amine is sp}3 _hybridized

_{The three groups and the unshared electron pair around nitrogen result in a}

tetrahedral geometry

_{If only the location of the groups (and not the unshared electron pair) are}

considered, the shape of the amine is trigonal pyramidal

_{Partial negative charge is localized in the region of the nonbonding electrons}

_{It is usually impossible to resolve amine enantiomers that are} chiral at nitrogen because they interconvert rapidly

_{The interconversion occurs through a pyramidalornitrogen inversioninvolving}

_{Quaternary ammonium salts can be resolved into enantiomers}

_{Chiral quaternary ammonium salts cannot undergo nitrogen inversion because}

they lack an unshared electron pair on the nitrogen atom

_{Basicity of Amines: Amine Salts}

_{Amines are weak bases}

_{Relative basicity of amines can be compared in terms of pKa} values for their respective conjugate acids

_{The more basic the amine, the higher the pK}

aof its conjugate acid will be

_{Primary alkyl amines are more basic than ammonia}

_{An alkyl group helps to stabilize the alkylaminium ion resulting from protonation}

_{In the gas phase, basicity in the family of methylamines increases} with increasing methyl substitution

_{More alkyl substitution results in more stabilization of the alkylaminium ion}

_{In aqueous solution, trimethylamine is less basic than dimethyl- or} methylamine

_{An alkylaminium ion in water is solvated and stabilized by hydrogen bonding of}

its hydrogens with water

Chapter 20 9

_{The trimethylaminium ion has only one hydrogen with which to hydrogen bond to}

water

_{The trimethylaminium ion is solvated less well (and therefore stabilized less) than}

_{Basicity of Arylamines}

_{Arylamines are weaker bases than the corresponding nonaromatic} cyclohexylamines

_{The unshared electron pair on nitrogen of an arylamine is}

delocalized to the ortho and para positions of the ring

_{The lone pair is less available for protonation, i.e., it is less basic}

_{Protonation of aniline is also disfavored because a protonated} arylamine has only two resonance forms

_{Basicity of Heterocyclic Amines}

_{Nonaromatic heterocyclic amines have approximately the same} basicity as their acyclic counterparts

Chapter 20 11

_{Amines versus Amides}

_{Amides are much less basic than amines}

_{The pK}

aof a protonated amide is typically about zero

_{One reason for this much lower basicity is that the amide is} greatly stabilized by resonance but the protonated amide is not

_{A more important reason for the weaker basicity of amides is that} the nitrogen lone pair is delocalized to the carbonyl oxygen

_{Amides are actually protonated at the oxygen atom}

_{Aminium Salts and Quaternary Ammonium Salts}

_{Protonation of amines with acids leads to formation of aminium} salts

_{Aminium salts are formed from 1}o_{, 2}o_{or 3}o _{amines and the aminium ion bears at}

least one hydrogen

Chapter 20 13

_{Quaternary ammonium salts have four groups on the nitrogen}

_{Quaternary ammonium halides are not basic because they do not} have an unshared electron pair on nitrogen

_{Solubility of Amines in Aqueous Acid}

_{Many aminium chlorides, bromides, iodides and sulfates are water} soluble

_{Amines which are not soluble in water will often dissolve in dilute aqueous acid}

_{Solubility of amines in dilute acid can be used as a chemical test} to distinguish amines from compounds that are not basic

_{Water-insoluble amines can be separated from water-insoluble}

Chapter 20 15

_{Water-insoluble amines can be separated from water-insoluble} neutral or acidic compounds by virtue of the amine’s solubility in aqueous acid

_{The amine is extracted into aqueous acid}

_{The amine is recovered by making the solution basic and extracting the amine}

into an organic solvent

_{Preparation of Amines}

_{By Nucleophilic Substitution Reactions}

_{Reaction of ammonia with an alkyl halide leads to an aminium salt The salt is treated with base to give the primary amine}

_{The method is limited because multiple alkylations usually occur}

_{Alkylation of Azide Ion followed by Reduction}

_{A primary amine is prepared more efficiently by reaction of azide anion with an}

alkyl halide and subsequent reduction of the alkylazide to the amine

_{The Gabriel Synthesis}

_{Primary amines can also be made cleanly by the Gabriel Synthesis}

_{The first step in the Gabriel synthesis is alkylation of potassium phthalimide Reaction of the N-alkylphthalimide with hydrazine in boiling ethanol gives the}

primary amine

_{Preparation of Aromatic Amines by Reduction of Nitro}

Compounds

_{Aromatic amines can be synthesized by reduction of the} corresponding nitro compound

_{Preparation of Primary, Secondary and Tertiary Amines}

through Reductive Amination

_{Aldehydes and ketones react with ammonia, primary or secondary} amines to yield imines or iminium ions

_{The imines and iminium ions can then be reduced to new primary, secondary or}

tertiary amines, respectively

_{The reduction can be accomplished using catalytic hydrogenation} or a hydride reducing reagent

_NaBH

_{Preparation of Primary, Secondary, or Tertiary Amines}

through Reduction of Nitriles, Oximes, and Amides

_{Reduction of nitriles or oximes yield primary amines}

_{Reduction of amides can yield primary, secondary or tertiary} amines

_{Reduction can be accomplished by using catalytic hydrogenation} or LiAlH₄

_{Reactions of Amines}

_{The lone pair of the amine nitrogen atom accounts for most} chemistry of amines

_{The unshared electron pair can act as a base or as a nucleophile}

_{Reactions of Amines with Sulfonyl Chlorides}

_{Primary and secondary amines react with sulfonyl chlorides to} produce sulfonamides

_{Eliminations Involving Ammonium Compounds}

_{The Hofmann Elimination}

_{An E2-type reaction occurs when a quaternary ammonium} hydroxide is heated

_{An amine is a relatively good leaving group}

Chapter 20 25

_{Hofmann elimination and other elimination reactions of charged} substrates proceed to give the least substituted double bond

_{This is called the Hofmann rule, and the least substituted alkene product is called}

Determining Structure using the Hofmann Elimination

N H

Excess CH₃I

N+

CH₃ CH₃

I

-Ag₂O

Chapter 20 27

Ag₂O

N+ CH₃ CH₃ OH -H N CH₃ CH₃

+H₂O

Using this information, we can work backwards

to determine a structure.

The alkaloid

coniine

_{is isolated from}

hemlock and has the molecular formula

C

H

N. Treatment of coniine with excess

methyl iodide, followed by silver oxide

methyl iodide, followed by silver oxide

and heating gives

N,N

-dimethyl-7-octene-4-amine. Propose a structure for coniine

and show how this reaction gives the

N coniine

Hofmann

N+ H

or N

+

H C₈H₁₇N

Chapter 20 29

N N H H N H N H

coniine H

N excess CH₃I

N+ I- Ag2O

heat