6,Introduction to Original Research
6.1,Olefin Epoxidation with Mn(salen) Complexes
Introduction,
Your "advisor" has carefully monitored your progress in 5.301 and believes that you are
ready to move from the technique modules to an actual project,This project will require you to use
many of the skills that you have learned over the past three weeks to address a specific question,In
addition,you and your labmates will learn to work as a research group in order to reach an
ambitious goal in a short period of time,
Overview,(written by your advisor)
Our group has had a longstanding interest in the epoxidation of olefins (eq 1),and would
like to take another look at an important report from a decade ago,Eric Jacobsen (former MIT
Post-doc and current Harvard Professor) showed that Mn(salen) complexes such as 1 are effective
epoxidation catalysts (eq 1),Because Mn(salen) complexes are easy to make,I am interested in
probing the relative reactivity of a series of different Mn(salen) derivatives,A graduate student in
the lab has investigated several Mn(salen) complexes,but I want you and your labmates to complete
a more comprehensive study,So,look over the attached Jacobsen paper,talk to the graduate
student on the project about the reactions you will be running,and be sure to organize your efforts
with your fellow labmates,Let me know what trends you discover,
H R
Epoxidation
H O R
(1)
Reaction
R H R H
Olefin Epoxide
H
3
C
tBu
tBu
1 salen =
(one of Jacobsen's Mn(salen) catalysts) bis(salicylaldehyde)ethylenediamine
N N
O O
Mn
Cl
CH
3
Ph
Ph
N N
O O
37
WARNING NOTICE,The experiments described in these materials are potentially hazardous and require a high level
ofsafety training,special facilities and equipment,and supervision by appropriate individuals,You bear the sole
responsibility,liability,and risk for the implementation of such safety procedures and measures,MIT shall have no
responsibility,liability,or risk for the content or implementation of any of the material presented,Legal Notices
Goals,
Synthesize a new salen complex (eq 2),and obtain a
1
H NMR spectra,
Synthesize the corresponding Mn(salen) complex (eq 3).
Compare isolated yields of the catalyst with your labmates.
Epoxidize stilbene using the published Jacobsen procedure and your catalyst (eq 4).
Determine the conversion of your reaction using
1
H NMR analysis,
Purify your crude reaction mixture by flash column chromatography,and obtain a yield.
Obtain a
1
H NMR spectrum of the pure epoxidation product,
Compare conversions and isolated yields with your labmates.
Use your results to make predictions about the correlation between catalyst structure and
catalyst efficiency,This will help us to plan better catalysts in the future,
Hints from Your Graduate Student Mentor,
1,Making the Salen Ligand (eq 2)
Reactions that you shouldn't try,(I had problems making the Mn(salen) complex with
these ligands.)
1) ethylenediamine + salicylaldehyde
2) trans-diaminocyclohexane + 3,5-di-tert-butyl,2-hydroxybenzaldehyde
3) ethylenediamine + nitrosalicylaldehyde
4) ethylenediamine + chlorosalicylaldehyde
You should aim to make 1.00 g of the Mn(salen) complex,Do your calculations based on
the two reactions proceeding in 70% overall yield,
There will be a large amount of solid produced,so use a large stir bar and fast stirring rate.
Don't forget that after the reaction finishes you'll need to add water to precipitate the
product,so don't start with too small a reaction flask,
When you first isolate the ligands (and later the metal complexes),they will be very wet,so
dry them overnight in your desiccator before you determine their weight,
Note the difference between ethanol and absolute ethanol,
38
OH O
Absolute
Ethanol N N
H
(2)
Reflux,1h
R
H
2
N NH
2
OH HOR
R
R = H,OMe,NO
2
,or Cl
Starting Materials,
Salicylaldehyde Derivatives,Diamines,
OH O OH O OH O OH O
H H H H
H
2
N NH
2
H
2
N NH
2
Cl NO
2
OMe
FW = 156.57 FW = 167.12 FW = 152.15 FW = 122.12 FW = 114.19 FW = 60.10
d = 1.219 d = 1.146 d = 0.951 d = 0.899
2,Making the Mn(salen) Complex (eq 3)
Some of our salen ligands behave a little differently than the ones Jacobsen describes,For
some cases toluene needs to be added to the hot ethanol solution to dissolve the ligand,
After the reaction is complete,it is crucial to cool the solution down to promote the
precipitation of the Mn(salen) complex,It's easiest to put the flask in an ice-bath for about
an hour,then filter the mixture,If no solids form after the ice-bath cooling,it may be
necessary to leave the solution in the fridge overnight,
1,Mn(OAc)
2
·4H
2
O
Air,Ethanol,Reflux,1h
N N N N
(3)
Mn
2,LiCl,Reflux,30 min
O ROH HOR R R O
Cl
39
3,Epoxidizing Stilbene (eq 4)
The best way to get the proper pH for this reaction is to use a pH meter,When it comes
time to do this step,the TAs can show you how to use our meter,
Monitoring this reaction by TLC can be tricky since the organic layer is on the bottom.
The best way to do it is to dip a pipet as deep as possible into the mixture,The liquid drawn
into the pipet by capillary action can then be rinsed into a vial using pentane,The less dense
organic phase will now be present on top of the aqueous phase and will be easy to obtain
using your TLC spotter,Note,we are only using this extravagant dilution procedure
because this is a biphasic solution in dichloromethane,Most homogeneous reaction
solutions (or biphasic mixtures with less dense organic solvents) can be directly spotted
onto TLC plates for analysis,
O
0.5 M Na
2
HPO
4
,Clorox
0.10 equiv,Mn(salen)
CH
2
Cl
2
,0 °C to RT
(4)
40
6.1,Olefin Epoxidation with Mn(salen) Complexes
Introduction,
Your "advisor" has carefully monitored your progress in 5.301 and believes that you are
ready to move from the technique modules to an actual project,This project will require you to use
many of the skills that you have learned over the past three weeks to address a specific question,In
addition,you and your labmates will learn to work as a research group in order to reach an
ambitious goal in a short period of time,
Overview,(written by your advisor)
Our group has had a longstanding interest in the epoxidation of olefins (eq 1),and would
like to take another look at an important report from a decade ago,Eric Jacobsen (former MIT
Post-doc and current Harvard Professor) showed that Mn(salen) complexes such as 1 are effective
epoxidation catalysts (eq 1),Because Mn(salen) complexes are easy to make,I am interested in
probing the relative reactivity of a series of different Mn(salen) derivatives,A graduate student in
the lab has investigated several Mn(salen) complexes,but I want you and your labmates to complete
a more comprehensive study,So,look over the attached Jacobsen paper,talk to the graduate
student on the project about the reactions you will be running,and be sure to organize your efforts
with your fellow labmates,Let me know what trends you discover,
H R
Epoxidation
H O R
(1)
Reaction
R H R H
Olefin Epoxide
H
3
C
tBu
tBu
1 salen =
(one of Jacobsen's Mn(salen) catalysts) bis(salicylaldehyde)ethylenediamine
N N
O O
Mn
Cl
CH
3
Ph
Ph
N N
O O
37
WARNING NOTICE,The experiments described in these materials are potentially hazardous and require a high level
ofsafety training,special facilities and equipment,and supervision by appropriate individuals,You bear the sole
responsibility,liability,and risk for the implementation of such safety procedures and measures,MIT shall have no
responsibility,liability,or risk for the content or implementation of any of the material presented,Legal Notices
Goals,
Synthesize a new salen complex (eq 2),and obtain a
1
H NMR spectra,
Synthesize the corresponding Mn(salen) complex (eq 3).
Compare isolated yields of the catalyst with your labmates.
Epoxidize stilbene using the published Jacobsen procedure and your catalyst (eq 4).
Determine the conversion of your reaction using
1
H NMR analysis,
Purify your crude reaction mixture by flash column chromatography,and obtain a yield.
Obtain a
1
H NMR spectrum of the pure epoxidation product,
Compare conversions and isolated yields with your labmates.
Use your results to make predictions about the correlation between catalyst structure and
catalyst efficiency,This will help us to plan better catalysts in the future,
Hints from Your Graduate Student Mentor,
1,Making the Salen Ligand (eq 2)
Reactions that you shouldn't try,(I had problems making the Mn(salen) complex with
these ligands.)
1) ethylenediamine + salicylaldehyde
2) trans-diaminocyclohexane + 3,5-di-tert-butyl,2-hydroxybenzaldehyde
3) ethylenediamine + nitrosalicylaldehyde
4) ethylenediamine + chlorosalicylaldehyde
You should aim to make 1.00 g of the Mn(salen) complex,Do your calculations based on
the two reactions proceeding in 70% overall yield,
There will be a large amount of solid produced,so use a large stir bar and fast stirring rate.
Don't forget that after the reaction finishes you'll need to add water to precipitate the
product,so don't start with too small a reaction flask,
When you first isolate the ligands (and later the metal complexes),they will be very wet,so
dry them overnight in your desiccator before you determine their weight,
Note the difference between ethanol and absolute ethanol,
38
OH O
Absolute
Ethanol N N
H
(2)
Reflux,1h
R
H
2
N NH
2
OH HOR
R
R = H,OMe,NO
2
,or Cl
Starting Materials,
Salicylaldehyde Derivatives,Diamines,
OH O OH O OH O OH O
H H H H
H
2
N NH
2
H
2
N NH
2
Cl NO
2
OMe
FW = 156.57 FW = 167.12 FW = 152.15 FW = 122.12 FW = 114.19 FW = 60.10
d = 1.219 d = 1.146 d = 0.951 d = 0.899
2,Making the Mn(salen) Complex (eq 3)
Some of our salen ligands behave a little differently than the ones Jacobsen describes,For
some cases toluene needs to be added to the hot ethanol solution to dissolve the ligand,
After the reaction is complete,it is crucial to cool the solution down to promote the
precipitation of the Mn(salen) complex,It's easiest to put the flask in an ice-bath for about
an hour,then filter the mixture,If no solids form after the ice-bath cooling,it may be
necessary to leave the solution in the fridge overnight,
1,Mn(OAc)
2
·4H
2
O
Air,Ethanol,Reflux,1h
N N N N
(3)
Mn
2,LiCl,Reflux,30 min
O ROH HOR R R O
Cl
39
3,Epoxidizing Stilbene (eq 4)
The best way to get the proper pH for this reaction is to use a pH meter,When it comes
time to do this step,the TAs can show you how to use our meter,
Monitoring this reaction by TLC can be tricky since the organic layer is on the bottom.
The best way to do it is to dip a pipet as deep as possible into the mixture,The liquid drawn
into the pipet by capillary action can then be rinsed into a vial using pentane,The less dense
organic phase will now be present on top of the aqueous phase and will be easy to obtain
using your TLC spotter,Note,we are only using this extravagant dilution procedure
because this is a biphasic solution in dichloromethane,Most homogeneous reaction
solutions (or biphasic mixtures with less dense organic solvents) can be directly spotted
onto TLC plates for analysis,
O
0.5 M Na
2
HPO
4
,Clorox
0.10 equiv,Mn(salen)
CH
2
Cl
2
,0 °C to RT
(4)
40
