Transcript Direct Conversion of Benzyl Alcohol to Amines via Lewis Acid

Direct Conversion of Benzyl Alcohol
to Amines via Lewis Acid Activation
James Awuah
Amy Hughes
Molly Plemel
Megan Radke
WESTERN WYOMING COMMUNITY COLLEGE
Outline
• Background
• Current Amine Syntheses
– Alkylation
– Gabriel Amine Synthesis
– Azido Reduction
• Proposed Research
• Experimental Conditions/Precedence
• Summary
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Background
• Derivatives of Ammonia
• Can be primary (1°), secondary (2°), or tertiary
H
(3°)
N
• Can be cyclic or acyclic
N
• Form quaternary ammonium salts
H
piperazine
H
N
H
R
N
H
R
N
H
R
N
R
H
H
R
R
ammonia
primary amine
secondary amine
tertiary amine
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Applications
OH
• Pharmaceuticals
NH
– Ephedrine
– Novocaine
– Fentanyl
• Agricultural Sciences
– Herbicides
– Pesticides
ephedrine
O
O
N
H2N
Novocaine
O
HO
H
N
O
P
OH
OH
glyphosate "RoundupTM"
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Applications Continued
• Industry
–
–
–
–
–
Photography developers
Water proofing agents
Fabric softeners
Chelating agents
Metal ligands
• Biological
–
–
–
–
Neurotransmitters
Amino acids
Proteins
Nucleotides
N
N
TMEDA
HO
NH2
HO
Dopamine
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Amine Reagents in Organic Synthesis
Li
Amines are commonly used
as bases and catalysts in
organic reactions.
N
N
N
N
LDA
N
DABCO
DBU
CF3
I
H
DABCO
+
F
dodecane, 130 0C
F
CF3
Sonogashira coupling
Luque, R.; Macquarrie, D. J. Org. Biomol. Chem. 2009, 7, 1627-1632.
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Current Amine Syntheses*
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•
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Alkylation*
Gabriel Amine Synthesis*
Reductive Amination
Alkyl Azide formation/reduction*
Nitrile Reduction
Amide Reduction
Hofmann Rearrangement
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Alkylation
Treatment of an amine with an alkyl halide or
alcohol electrophile resulting in N-C bond formation
• Pros
– Achievable on an industrial scale with select reagents
• Cons
– Direct alkylation with alcohols often require expensive
catalyst(s) and/or harsh conditions
– Low selectivity (over-alkylation)
R
H
N
H
H
R
X
R
N
H
H
R
N
R
H
R
N
R
R
R
N
R
R X
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Harsh Conditions/Expensive Catalyst
OH
NH3
NH3, Catalyst( 0.1 mol%) 135 oC
Reaction requires specialized apparatus, high pressure,
elevated temperature, and long reaction times. Limited
to primary amines.
Cl
N
Ru
P
P
H
O
Ruthenium Catalyst Complex
Gunanathan, C.; Milstein, D. Angew. Chem. 2008, 120, 8789-8792.
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Gabriel Amine Synthesis
Alcohol is converted to alkyl halide, allowed to react
with a metal phthalimide, then hydrolyzed to
provide the amine.
• Pros
– Metal phthalimides are readily available
– Selective (over-alkylation not observed)
• Cons
– General procedure gives only 1° amines
– Several steps required
O
NH
O
1) KOH
2) R-X
3) NaOH
R
NH2
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Amines from Azides
Alkyl halide treated with sodium azide to form an
azido compound. Subsequent reduction provides
the corresponding amine.
• Pros
– Sodium azide is readily available
– Efficient and generally reliable
• Cons
– Limited to 1° amines
– Azides, esp. low MW azides are explosive and impactsensitive
– Multiple steps required
R
X
NaN3
R
N3
LAH
R
NH2
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Direct Amination-Lewis Acid Mediated
Approach
X
N3
reduction
OH
NH2
NH3, Lewis acid
X
hydrolysis
O
N
O
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Experimental Conditions
• Proposal
– Use benzyl alcohol as electrophilic reagent
– Implement ZnI2 as the Lewis acid for preliminary
investigation
– Explore ammonia as well as 1°, 2°, and 3° amines
as nucleophilic reagents
– Vary conditions (solvent, temperature,
concentration, etc.) to maximize conversion.
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Precedence
• Previously published research
– Use of zinc halides and benzylic alcohols
• Previous nucleophiles used in parallel
reactions
R Se
– Thiols
R
selenide
– Alcohols
– Selenols
R'
– Phosphites
O
P
OR
OR
phosphonate
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Periodic Table of the Elements
http://commons.wikimedia.org/wiki/File:Periodic_table_sl.svg
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Characterization
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Thin Layer Chromatography (TLC)
Gas Chromatography (GC)
Infrared Spectroscopy (IR)
Nuclear Magnetic Resonance (NMR)
Mass Spectrometry (MS)
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Summary
• Efficient and direct synthesis of amines
• Proposed Research
– Use of ZnI2 and benzyl alcohol
• No special apparatus required, mild
conditions, inexpensive
• Various methods to check products and
progress
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Acknowledgements
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INBRE
Western Wyoming Community College
Professor Rocky Barney
Audience
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