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TRANSCRIPT
Rapid Regioselective Oxidations of Secondary Alcohols
with Polymeric DABCO-Bromine Complex (PDB)
Apryl Bronley-DeLancey The University of Tampa Department of Chemistry
What is oxidation?
The outcome of oxidation reactions of alcohols depends on the substituents on the carbinol carbon.
In order for each oxidation step to occur, there must be H on the carbinol carbon.
*http://www.chem.ucalgary.ca/courses/351/Carey/Ch15/ch15-4-6.html
Aldehydes and Ketones
H3CCCH3
O
HCH
O
Formaldehyde Acetone
Aldehydes must have at least one hydrogen bound to the carbonyl carbon.
Ketones have two carbons bound to the carbonyl carbon
•Primary alcohols can be oxidized to aldehydes or further to carboxylic acids. In aqueous media, the carboxylic acid is usually the major product. PCC or PDC, which are used in dichloromethane, allow the oxidation to be stopped at the intermediate aldehyde.
*http://www.chem.ucalgary.ca/courses/351/Carey/Ch15/ch15-4-6.html
•Secondary alcohols can be oxidized to ketones but usually no further •Tertiary alcohols cannot be oxidized (no carbinol C-H)
NBr2
N NBr Br2CH2Cl2, 0o C
+-
Bisquinuclidiniumbromine(I) Bromide"BQBB"
Hypervalent (10 e-) bromine is a good source of "active bromine", a mild oxidant.
Stable, decomposition resistant, yellow/orange solid.
Shown to be somewhat selective in oxidizing 2o alcohols over 1o alcohols
R R
OH
H R H
OH
H+
0.5 eqiv. BQBBCH2Cl2/H2O R R
O
R H
OH
H+
(1) "Selective oxidation of secondary alcohols by bis(quinuclidinium)bromine(I) bromide. A 2-coordinate bromine(I) positive halogen reagent." Blair, L. K.; Bledsoe, R. K.; Burberry, K.; Struss, J. A., Unpublished.(2) Blair, L. K.; Hobbs S.; Bagnoli, N.; Husband, L.; Badika, N. J. Org. Chem. 1992, 57, 1600.
“BQBB” Synthesis and Utility
R H
O
R
R R
O
H RN RR
-H+
+H+ R H
O
R
- RN RR
Br +
R H
O
R
Br
RN RR
RN RR
H Br
Rate of reaction is slow in CH2Cl2; may rely on disassociation of BQBBRN RR
BrRNRR R
N RR
Br +
RNRR
Rates and yields are enhanced by running reactions in biphasic CH2Cl2/H2O
Rates enhanced by adding H+ catalyst (PPTS) or stochiometric amounts of Ag+ (AgBF4).
Oxidations with BQBB
Alcohol Product Cat./ Reagent
Reaction Times
Yield %
2-pentanol 2-pentanone AgBF4 5 min. 90
2,4-dimethyl-3-pentanol
2,4-dimethyl-3-pentanone
AgBF4 5 min. 100
cyclopentanol cyclopentanone PPTS 3 hrs. 97
2-pentanol 2-pentanone PPTS 3 hrs. 95
1-pentanol pentanal AgBF4 5 min. 65
1-octanol octanal AgBF4 5 min. 51
CH2Cl2/H2O (PPTS)CH2Cl2 (AgBF4)
BQBB
R R'H
R R'
OOH
Oxidations with BQBB
Polymeric DABCO Bromine Complex
NN N2 Br2
NBr BrCCl4, 25o C
+
Polymeric DABCO Bromine Complex"PDB"
N N
N
Hypervalent (10 e-) bromine/Br3- is a good source of two equivalents of
"active bromine".
Ionic polymer, stable, decomposition resistant, yellow, insoluble solid.
Shown to be very selective in oxidizing 2o alcohols over 1o alcohols
Reactions are extremely slow (~4-80 hrs.) probably due to poor solubility.
Oxidations required additional DABCO.
Br3-
2-4 equiv. DABCO0.5 equiv. PDB, CH3CN, 25o - 50oC
R R'H R R'
OOH
Alcohol Rxn. Time % Yield Ketone/Aldehyde
% Mass Balance
89 hrs 56% 91%
15.5 hrs 70% 95%
3 hrs 52% 100%
16 hrs 26% 80%
3.2 hrs 10% 81%
3.0 11% 77%
OH
OH
OH
OH
OH
CH3 CH2 CH2 OH5
3 equiv. DABCOCH3CN, 50oCR R'
HR R'
OOH 0.5 equiv. PDB
Blair, L. K.; Baldwin, J.; Smith, W. C. J. Org. Chem., 42, 1816, 1977.
Literature Summary
BQBB reactions involving "catalytic" PPTS employed 1.1 equivalents . in biphasic CH2Cl2/H2O.
BQBB/AgBF4 reactions performed in the absence of H2O.
PDB reactions performed without catalysts or coreagents in the absence of H2O.
PDB reactions required additional amine (DABCO) to aid reaction and remove HBr as reactions progressed.
Explore catalyst loading for BQBB oxidations.
Mimic BQBB reaction conditions for PDB oxidations.
Use 2-pentanol as a basis system, then expand to other alcohols and diols.
Explore the use of chiral amines to construct asymmetric oxidants.
Explore PDB and/or BQBB as oxidants to convert amines to imines and/or aldehydes and ketones.
Research Objectives
Catalyst Loading with BQBB
1.1 equiv. BQBBOH O
PPTS, CH2Cl2/H2O2 hr.
Equiv. Catalyst Recovered Alcohol
% Yield Ketone Mass Balance
1.1 27.8 83.4 111.20.5 29.0 78.2 107.2
0.25 22.8 81.6 104.40.1 26.5 76.7 103.2.01 32.7 75.3 108.00 27.3 77.8 105.1
0 (no H2O) 94.8 7.3 102.1
OHOH
OH
OH
OH
OH
OH
Recovered Alcohol: % Yield Ketone: Mass Balance:
19.9% 94.4% 114.3%
43.7% 21.1% 64.8%
0.0% Quant.*
27.2% 65.5% 92.7%
24.1% 48.0% 72.1%
23.3% 63.6% 86.8%
37.5% 53.5% 91.0%
Recovered Alcohol: % Yield Ketone: Mass Balance:
- Reacts Rapidly - Product May React Further
CH2Cl2/H2O, 25oC
0.55 equiv. PDB
R R'H R R'
OOH
2 hr rxn time
With PDB. . . Just Add Water
OH
OH
OH
OH
OH
OH
Recovered Alcohol: % Yield Ketone: Mass Balance:
4.1% 93.9% 98.0%
0.0% 90.3% 90.3%
8.3% 84.9% 93.2%
0.0% 89.3% 89.3%
0.0% 83.9% 83.9%
3.2% 83.7% 86.9%
Recovered Alcohol: % Yield Ketone: Mass Balance:
CH2Cl2/H2O, 25oC
0.55 equiv. PDB
R R'H R R'
OOH
20 hr. rxn time
20 Hour Oxidations of Secondary Alcohols
CH2Cl2/H2O, 25oC
0.55 equiv. PDB
R HH R H
OOH
OHOH
OHOH
79.9% 8.7% 88.6%
63.3% 28.9% 92.2%
0.0% 97.1% 97.1%
84.3% 7.3% 91.6%
Recovered Alcohol: % Yield Aldehyde: Mass Balance:
2 hr. Oxidations
20 hr. Oxidations
67.1% 26.9% 94.0%
14.2% 85.3% 99.5%
0.0% 91.5% 91.5%
53.8% 44.0% 97.8%
Recovered Alcohol: % Yield Aldehyde: Mass Balance:
Oxidations of Primary Alcohols
OH 0.55 equiv. PDB
CH2Cl2/H2O, 25 oC
15 min.
O
OH0.55 equiv. PDB
CH2Cl2/H2O, 25 oC
15 min.
O
No recovered alcohol! Quantitative after 15 min.?
86.0 % recovered alcohol 9.6% yield
Allylic Alcohols vs. Benzyl Alcohols
Reactivity of Benzyl SystemsPiano stool complexes are common for many oranometallic complexes h5 and h6 examples:
ML
LL M
L LM
LLL M
L L
Could the bromine(I) of PDB and BQBB behave similarly slowing the rate of reaction? For example:
Br
N N
OH
Metallic Bromine?!?!?
Can we synthesize the following complex to verify a previously undiscovered metallic-like behavior of bromine?
BrN NBr-- Na +
BQBB Na+NaH
-H2
+
X-Ray crystallography studies of the cyclopenadienyl-BQBB complex should verify the presence of the first bromine(I) piano stool complex.
Conclusions
BQBB oxidations do not require PPTS catalyst or co-reagents when performed in biphasic CH2Cl2/H2O.
PDB oxidations are much faster in biphasic CH2Cl2/H2O compared to CH3CN/DABCO system.
Rates of oxidation using PDB appear to favor allylic alcohols over benzylic and secondary alcohols. The piano stool complexing phenomenon may explain this behavior.
Oxidations appear to be very sluggish with primary alcohols.
Future Directions
R R'
NH2
H
[O]
R R'
NH
R R'
O
Active bromine complexes have been reported to oxidize amines to ketones or aldehydes. Can the biphasic PDB system acheive this? .
Reports suggest an imine intermediate, yet the imine is not isolated. If this oxidation works, can we stop at the imine?
Asymmetric BQBB-like Oxidants
N
N
TBSO
N
OTBSN
Br
Br -
N
N
TBSO Br22
N NBr2 N N
Br+
-Br
Can we construct asymmetric oxidants using sparteine or cinchona alkaloid derivatives?
Sparteine reaction has been attempted: Very exothermic! Produces a thick . orange semi-solid.
The reaction between quinidine derivative and bromine is low yielding.
None of these asymmetric oxidants have been characterized.
AcknowledgementsMatt DeLancey W. David Barnhart Mike Palmer (Sun Labs) The University of Tampa (Delo Grant) Dr. John Struss Dr. Larry Blair (Berea College)
http://www.staff.livjm.ac.uk/pacfisma/cartlnk.html