Chapter 19 OCHEM 2

amines

organic derivatives of ammonia with one or more alkyl or aryl groups bonded to the nitrogen atom.

heterocyclic amine

the nitrogen atom is apart of the aliphatic ring or aromatic

cyclohexylamine

primary amine

piperidine

secondary amine

quinuclidine

tertiary amine

Quaternary (4°) ammonium salts

have four alkyl or aryl bonds to a nitrogen atom, the nitrogen atom bears a positive charge

ethylamine

CH3CH2NH2

diisopentylamine

bemzylamine

aziridine

pyrrole

pyrrolidine

N-methyl pyrrolidine

imidazole

indole

pyridine

methyl pyridine

pyrimidine

purine

structure of amines

nitrogen in amines forms 3 sigma bonds and has 1 lone pair, with sp³

amine dipole moments

strongly polar due to hydrogen bonds and the lone pair on nitrogen

amine functions

Bronsted Lowry base and accepts a proton

amine basicity

sp < sp 2 < sp 3

amine solubility

Increasing the number of alkyl groups decreases solvation of ion, so 2° and 3° amines are similar to 1° amines in basicity

amine resonance

Any delocalization of the electron pair weakens the base

less basic than most aliphatic amines.

Aniline is

a very weak base

pyrrole is

amine salt ions

the protonated amine cation and the anion derived from the acid

amine IR N-H

3200-3500

NMR N-H

1-4

C13 N-H

30-50

amine MS

alpha cleavage

EAS Arylamines

Protonation of the amine under acidic conditions converts the group into a strong deactivator, multiple substitution is a problem

EAS Arylamines conditions

excess X2, NaHCO3

excess X2, NaHCO3

EAS Arylamines conditions

EAS w/ excess X2, NaHCO3

tri-substituted X

EAS of Arylamines mechanism

Step 1: Attack takes place at the 3-position.
Step 2: Loss of a proton gives the product.

NAS of Arylamines mechanism

Step 1: Nucleophilic attack at the 2-position (or the 4-position) forms a stabilized
intermediate.
Step 2: Expulsion of the leaving group gives the product

amines + 1 alkyl halides

ammonium halides

direct alkylation

some amine molecules will react once and some twice, giving mixed results

exhaustive alkylation

A mild base (often or dilute NaOH) is added to deprotonate the intermediate alkylated amines and to neutralize
the large quantities of HX formed

Excess ammonia alkylation

10 moles of ammonia with one mole of R—X

Acylation of amines product

amide

mechanism of acylation of amines

Step 1: A nucleophile attacks the strongly electrophilic carbonyl group of the acid
chloride to form a tetrahedral intermediate.
Step 2: The tetrahedral intermediate expels chloride ion.
Step 3: Loss of a proton gives the amide

sulfonamides

amides of sulfonic acid

Hofmann elimination

the elimination of a quaternary ammonium hydroxide in a concerted E2 reaction with amine as the leaving group

Hofmann product

least substituted alkene as the major product

Zaistev product

most substituted alkene as major product

hofmann elimination primary amine product

alkene + amine

hofmann elimination secondary amine product

opened ring alkene + substitution on the nitrogen

Hofmann elimination conditions

amine + -OH under heat

amine + -OH under heat

Hofmann elimination

Zaitsev elimination conditions

sodium methoxide + amine or alkyl halide

primary amine oxidation

oxidize easily, but complex mixtures of products often result

secondary amine oxidation

are easily oxidized to hydroxylamines, side products are often
formed, however, and the yields may be low

tertiary amine oxidation

are oxidized to amine oxides with good yields

common oxidizing agents

H2O2, MCPBA, MnO4-, RCO3H

1° amine + [O]

(R—NHOH) hydroxylamine

2° amine + [O]

(R2—NOH) 2° hydroxylamine

3° amine + [O]

(R3—O-) 3° hydroxylamine

cope elimination

reaction where an amine is oxidized to an intermediate called
an “N-oxide”, which, when heated, acts as the base in an intramolecular E2 elimination reaction to give a new alkene

cope elimination product

least substituted product

primary amines + nitric acid (HNO2) product

dialkyldiazonium salts, that decompose into carbocations and nitrogen

secondary amines + nitrosomium ion (N+)=O product

secondary N-nitrosoamines

Mechanism of Diazotization of primary amine

Part 1: Attack on the nitrosonium ion (a strong electrophile), followed by deprotonation, gives an N-nitrosoamine.
Part 2: A proton transfer (a tautomerism) from nitrogen to oxygen forms a hydroxy group and a second bond.
Part 3: Protonation of the hydroxy group, followed by loss of water, gives the diazonium ion.

Arenediazonium salts

relatively stable in aqueous solutions around 0-10 Celsius

arene diazonium salt

ArN2 + H3O+ warm product

phenols

ArN2 + CuCl product

aryl chlorides

ArN2 + CuBr product

aryl bromides

ArN2 + CuCN product

benzonitriles

ArN2 + HBF4 product

aryl fluorides

ArN2 + KI product

aryl iodides

ArN2 +H3PO2 product

aryl group

deamination

process of removing an amine group (NH2)

ArN2 + AR—H product

azo dyes ( Ar—N==N—Ar )

hydrolysis product

replaces the NH2 group with a hydroxide group

amine hydrolysis conditions

(1) H2SO4, heat, H2O

(1) H2SO4, heat, H2O

amine hydrolysis conditions

Sandmeyer product

replace the amine group (NH2) with Br, Cl, CN

sandmeyer conditions

(1) NaNO2. HCl (2) CuCl

(1) NaNO2. HCl (2) CuCl

sandmeyer conditions

Deamination reaction product

removal of the NH2 group on the compound

deamination reaction conditions

(1) NaNO2, HCL (2) H3PO2

(1) NaNO2, HCL (2) H3PO2

deamination reaction conditions

Diazo coupling product

nitrogen double bond with two rings

Reductive amination

most general synthesis , capable of adding a primary or secondary alkyl group to an amine

Reductive Amination: 1° Amines

LiAlH4 or NaBH3 CN can be used to reduce the oxime

Reductive Amination: 2° Amines

LiAlH4 or NaBH3 CN can be used to reduce the oxime

Reductive Amination: 3° Amines

NaBH(OAc)3 CH3COOH is used to reduce the salt

reduction hydroxylamine to

primary amine

reduction of primary amine to

secondary amine

reduction of a secondary amine to

a tertiary amine

1° Amines by Acylation-reduction

acid chloride + ammonia

2° Amines by Acylation-reduction

acid chloride + primary amine

3° Amines by Acylation-reduction

acid chloride + secondary amine

Gabriel Synthesis

involves reacting a potassium phthalimide with an alkyl halide, followed by hydrolysis or hydrazinolysis to remove the phthaloyl group and yield the desired primary amine

Reduction of Azides

React azide with unhindered 1° or 2° halide or tosylate (SN2) and with reduction yield a primary amine

reduction of nitriles

React nitrile with unhindered 1° or 2° halide or tosylate (SN2) and with reduction yield a primary amine

azide

Azide ion, –N 3 , is a good nucleophile