Post on 06-Jul-2018
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CHAPTER 25: AMINES
GENERAL INFO
EXAMPLES OF AMINES
Fish smell Trimethylamine from decay of
trimethylamine oxide (osmolyte) Decay compound
Serotonin Neurotransmitter, feeling of
happiness
Psilocin Hallucinogenic mushrooms
5-MeO-DMT Psychedelic found in the skin
of Bufo alvarius toad
Mescaline Hallucinogenic in peyote
cactus
Nightshade berries
“Nightlock berries” from the Hunger Games
Deadly Nightshade Contains atropine (+2
related compounds) which cause delirium and
hallucinations
Hemlock plant
Hemlock Contains poison coniine, Used to execute Socrates
(philosopher).
MeNMe
MeO Me
NMe
Medecay H2N
NH2OH
O
H2N
NH2
Lysine (amino acid)
decay
Cadaverine
H2N
NH2
Putrescine
MeN
O
O
Ph
OH
NH
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NOMENCLATURE 1. Common system for simple amines: order alkyl groups alphabetically. “Alkyl alkyl amine”
2. IUPAC: Ending is –amine.
3. Use “N-alkyl” and consider it a substituent for 2˚ and 3˚ amines.
Common: IUPAC:
CHIRALITY1
1 Nitrogen LP inversion: Jones, M., Fleming, S.A., Organic Chemistry, 4th ed., Norton, 2010, pp. 254. Phosphorous chirality: Carey, F.A., Sundberg, R.J., Advanced Organic Chemistry, 4th ed., Kluwer Academic/Plenum Publishing, 2000, pp. 103.
PCH3H P
H3CH
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TRENDS IN BASICITY
WHY ARE AMINES BASIC? Amines are the only mainstream functional group that produce a noticeably basic aqueous solution, which can be verified by litmus paper.
NH3 + H2O
CH3OH + H2O
BASICITY TRENDS
ALKYL VS. ANILINE
CH3CH2NH2
pKb
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HYBRIDIZATION DIFFERENCES
piperidine
pyridine
acetonitrile
pKb
AVAILABILITY CONSIDERATIONS
pyridine
pyrrole
acetamide
pKb
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SUMMARY
Problem: which compound is more basic in each set?
Set A Set B
Set C Set D
APPLICATION: UREA CYCLE
O
OH3N
R
generic amino acid
metabolismO
OH3N
glutamate
NAD+O
OO
OO OO
H2O+ NH3
urea cycle
α-ketoglutarate
H2N NH2
O
urea
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SYNTHESIS OF AMINES
CHALLENGES OF SN2
THROUGH A NITRILE
GABRIEL SYNTHESIS
Concept of “Atom Economy”
One of the tenets of Green Chemistry is the consideration of how many atoms are incorporated into the desired product (in comparison to how many atoms are “wasted”). This idea was proposed by Dr. Barry Trost (American chemist at Stanford). The Gabriel Synthesis is a poor reaction in terms of its atom economy.
I NH3
Siegmund Gabriel (German chemist)
Rxn published in 1887
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REDUCTIVE AMINATION
REACTION + MECHANISM
EXAMPLES
HNO
H
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BREAKING BAD
Pseudoephedrine Methamphetamine (Sudafed, decongestant) (psychostimulant)
“P2P Synthesis”
APPLICATION: BIOSYNTHESIS OF GLUTAMIC ACID
α-ketoglutaric acid
SUMMARY OF SYNTHESES
Synthesize this amine using three different methods:
1. Using a Nitrile
2. Using the Gabriel Synthesis
3. Using a Reductive Amination
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AMINE REACTIONS
ACID-BASE REACTIONS
APPLICATION: LEMON AND FISH
fish smell citric acid (in lemon)
APPLICATION: HYDROCHLORIDE SALTS
Diphenylhydramine-hydrochloride
Antihistamine used for allergies
Cetirizine-dihydrochloride Antihistamine used for allergies
Loperamide Anti-diarrheal
NHHCl HBr
N
+
O
HO
OH O
OHO
OH
NMeMe
Me
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APPLICATION: COCAINE
Free basing; smoking
“Crack” cocaine
→
⟵
Cocaine
Snorting; Injecting
HOFMANN ELIMINATION
Product distribution2
MECHANISM OF Ag2O STEP
EXAMPLES
2 Jones, M., Fleming, S.A., Organic Chemistry, 4th ed., Norton, 2010, pp. 324.
NH2 a. excess CH3I
b. Ag2O, H2O
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HOFMANN ELIMINATION CYCLES What is formed when this amine is treated to 3 “cycles” of Hofmann elimination?
DIAZONIUM SALTS
REACTION + MECHANISM
Nitrosamines (carcinogens) may be formed in the stomach from reaction of nitrites:
N
H
CH3
NaNO2
HClN
CH3
NO
a nitrosamine
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SYNTHESIS PROBLEMS
APPLICATION: DIAZO DYES
Para Red The first azo dye (1880);
used to dye cotton
Methyl Orange pH indicator
Sunset Yellow Food coloring. Chemically similar to a possible carcinogen, so limited usage.
NN OH
NN
OH
H
Cl
NN
OH