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The Effect of 15-crown-5 ether on the reactivityof a Grignard reagent
Victoria Johnson
Dirt Poor Company
A division of San Jose State University
San Jose, CA 95192December 8, 2008
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Overview of Presentation
• Review of the Grignard Reagent
• Discussion of current experiment
• Results• Conclusions
• Future Work
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Review of the GrignardReagent
Discovered by Victor Grignard in 1900
Won the Nobel Prize in 1912
One of the most important organometallic
Reagents used Used in making new C--C bonds
Over 40,000 papers published usingGrignard Reagents
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Synthesis of a GrignardReagent
RX + Mg(s) R-X Mg(s) R MgX(s)
R
RMgX (soln)
a b
c
d
e
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Side ReactionIn Synthesis of Grignard Reagent
Wurtz Coupling
Addition of carbanionto organohalide
Bromobenzene givesrise to biphenyl
R + RX R 2
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Schlenk Equilibrium
Grignard reagentsexist in two forms
Either form will react
Presence of dioxanepushes equilibrium tothe right
O ODioxane
2RMgX R 2Mg + MgX2
15-crown-5 etherO
O
O
O O
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Reactions involving GrignardReagents
C
O
R R
C
O
R O
R
C
O
R Cl
1. R MgX
2. H+C
R
OH
R
R
R MgX
C
O
R R
1. R MgX
2. H+
C
R R
OH
R
R MgX
C
O
R R
1. R MgX
2. H+C
R R
OH
R
ROH
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Current Experiment:Starting Point
In Presence of bis[2-(N,N-dimethylaminoethyl)] etherreaction stops at formation of ketone
No tertiary alcohol produced
Yields in range of 70 - 90%
Cl
O
R'MgX
THF
O
R'
N
O
N
RR
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Reactivity of Grignard is decreased throughcomplexation with ligand
Tridentate ligands work best
No success with bidentate ligands
Mode of action
N
O
N
Mg
R X
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Synthesis of Ketones
Acid Chlorides areinexpensive to make
Grignardsynthesis/reaction fastand easy
R
OH
R
O
R' R'
PCC
CH2Cl2
R
OH
R
O
R' R'
CrO3
H2SO4
CH3CCl
O
O
AlCl3
Heat
O
H3O+
HgSO4
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Experimental Options
Make ligand and reactwith differentsubstrates
Try “stock” ligand(s)
and react with benzoylchloride, other
substrates
18-crown-6
15-crown-5
O
O
O
O
O
O
O
O
O
O O
18
18-crown-6
15-crown-5
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Procedural Outline
Grignard reagentdivided into twoportions
Allowed to complex for15 minutes at 0 C
Added over 15 minuteperiod to substrate at -
60 C 1:1 ratio
MgBr
THF +15-crown-5at 0 C
THFat 0 C
O
Cl
O
Cl
-60 C
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Results, Expt. 1
White precipitate formed duringcomplexation period
More seen with 15-crown-5 ether GC indicated no formation of product,
though presence of small amount of
biphenyl
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Expt. 1:Analysis
Formation of precipitate: Grignard reagent cancome out of solution at cold temperatures
With 15-crown-5 ether, schlenk equilibriumprobably a factor
Biphenyl likely indicates successful synthesis ofgrigard reagent
Suspect purity of benzoyl choride
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Experimental changes
Litmus test of benzoyl chloride gives acidicresults!
TLC gives two spots
Methyl benzoate chosen as new substrate Less reactive, but able to obtain brand new bottle
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Plan B
Same prodedure asprevious expt.
GC indicates presence
of biphenyl GC aslo indicates very
small amount ofbenzophenone but not
able to confirm by GC-MS
MgBr
THF +15-crown-5at 0 C
THFat 0 C
-60 C
O
OCH3
O
OCH3
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Plan B:analysis
Not making as much Grignard as assumed
Reaction temperature too low Overhandling of Grignard
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Plan C:Final Attempt
No additional THF toGrignard
No pre-chilling of
Grignard reagent 2.3 : 1 ratio of
Grignard to substrate
One set at room temp,
one at 0 C
MgBr
THF +15-crown-5Room Temp
Grignard onlyRoom Temp
O
OCH3
O
OCH3
Grignard onlyRoom Temp
THF +
15-crown-5Room Temp
O
OCH3
O
OCH3
RoomTemp
0 C
RoomTemp
0 C
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QuickTime™and aTIFF (Uncompressed) decompressor
are needed to see this picture.
GC-MS Results:
Grignard with 15-crown-5 etherat room temperature
Triphenylmethanol
QuickTime™ and aTIFF (Uncompressed) decompressor
are needed to see this picture.
Methyl Benzoate
QuickTime™ and aTIFF (Uncompressed) decompressor
are needed to see this picture.
Biphenyl
QuickTime™and aTIFF (Uncompressed) decompressor
are needed to see this picture.
O
Benzophenone
O
O
CH3
OH
Starting Material
desired productunwanted product
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GC-MS Results:
Grignard without ligand at 0 C
QuickTime™ and a
TIFF (Uncompressed) decompressorare needed to see this picture.
O
O
CH3
Methyl BenzoateQuickTime™ and a
TIFF (Uncompressed) decompressorare needed to see this picture.
Biphenyl
QuickTime™ and aTIFF (Uncompressed) decompressor
are needed to see this picture.
QuickTime™ and aTIFF (Uncompres sed) decompressor
are needed to see this picture.
O
Benzophenone
OH
Triphenylmethanol
Starting Material
Starting material
Intermediate productExpected product
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Results
Ratio of Benzophenone to Triphenylmethanol
With crown ether, 0 C - 10 : 0.86
With crown ether, RT - 10 : 1.16
No crown ether, 0 C - 1 : 5.00
No crown ether, - RT 1 : 5.73
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Conclusions
Temperature appears to have effect on yield -more unreacted methyl benzoate at lowertemperatures
Grignard with 15-crown-5 reduces reactivity togive very low yields with methyl benzoate
Does not completely inhibit production of tertiaryalcohol
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Future Work
Obtain fresh benzoyl chloride
Try 18-crown-6 ether
Try to synthesize bis[2-(N,N-dimethylaminoethyl)] ether and work withdifferent substrates
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Thank You
My benchmates: Jamie, Monika, and Anne
Dr. Okuda Dr. Brook
And especially Dr. Straus
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