This week’s schedule:
Section
Wed. evening (Mar. 23)
Ferrocene Expt.
(run colums)
Expt. 16 (prep
clathrate)
Lab notebook
collection
(Expts 4, 5, 15
&intro toGCMS
Fri. afternoon (Mar. 25)
Expt. 13 & 16
Mon. afternoon (Mar. 28)
Expt. 13 & 16
Mon. evening (Mar. 28)
Expt. 13 & 16
Tues. afternoon (Mar. 29)
Expt. 21
Wed. evening (Mar. 30)
Expt. 16 (part
2) & 21
Fri. afternoon (Apr. 1)
Expt. 21
Mon. afternoon (Apr. 4)
Expt. 21
Mon. evening (Apr. 4)
Expt. 21
Tues. afternoon (Apr. 5)
finish 16 & 21
Expt. 21 – Dehyd ration of
Methylcyclohexanols and the Evelyn Effect
Elimation Reactions
Zaitzev’s Rule: When HZ is removed from a
molecule to form an alkene, the hydrogen is
lost preferentially from the carbon with
fewer hydrogens.
I
KOH
CH3CH=CHCH3
+
major
minor
This reaction is regioselective (produces
one regioisomer preferentially over one or
more other possible regioisomers). In most
cases, the thermodynamically most stable
isomer is the major product in such
reactions.
CH3
CH3
NaOEt, EtOH
CH3
100%
no
is formed
Cl
CH(CH3)2
CH(CH3)2
CH(CH3)2
Menthyl chloride
This reaction is an example of the E2
mechanism.
CH3
CH3
CH3
NaOEt, EtOH
78%
+
22%
Cl
CH(CH3)2
neomenthyl
chloride
CH(CH3)2
CH(CH3)2
Zaitzev’s Rule is followed in this case.
Neomenthyl chloride reacts much more
rapidly than menthyl chloride. What do
these results tell us about the reaction
mechanism?
CH3
exists in two chair conformers with one
being much more stable than the other.
Cl
CH(CH3)2
menthyl
chloride
H
iPr
H
H
iPr
H
CH3
H
H
H
Cl
H
H
major conformer
Cl
H
minor conformer
CH3
The chloro group is anti-periplanar to a
hydrogen (a requirement for the E2
mechanism) only in the minor conformer.
Because only the minor conformer reacts,
the reaction rate is quite low and leads to the
formation of only one product.
On the other hand, the major conformer (but
not the minor) of neomenthyl chloride can
react by the E2 mechanism. It can eliminate
via two different pathways.
H
iPr
Cl
H
iPr
H
CH3
H
H
Cl
H
H
OEt
H
major conformer
H
H
CH3
minor conformer
Zaitzev’s Rule is followed since it leads to
the more stable alkene product.
In 1994, Prof. David Todd ( then a chemistry
professor at Pomona College) was distilling
a mixture of 2-methylcyclohexanol and acid
to obtain the alkene products when he was
invited to lunch by the dept. secretary. He
stopped the distillation and went to lunch.
When he returned, he switched receiving
flasks before resuming the distillation. After
working up bo th fractions, he was surprised
to discover the second fraction contained
much less of the expected major product, 1methylcyclohexene than the first. Prof.
Todd named this unexpected result the
“Evelyn Effect” after the dept. secretary.
CH3
CH3
CH3
OH
mixture of
cis and trans
H3PO4
+ H2O
+
1-methyl
cyclohexene
3-methyl
cyclohexene
Up until this point, this reaction had been
considered to be a good exa mple of
Zaitzev’s Rule and the E1 mechanism in
alcohol dehydration reactions.
Closer examination reveals that when 2methylcyclohexanol and phosphoric acid is
distilled, the first 10% of the distillate is
~93% A, while the last 10% is only ~55%
with most of the remainder being B, along
with a trace of C.
CH3
CH3
OH
H3PO4
CH3
+
+
A
CH2
B
C
trace
Previous researchers had reported that cis-2methylcyclohexanol undergoes dehydration
much more rapidly than the trans isomer.
H
H
H
H
H
H
CH3
H
H
H
H
H
OH2
major conformer
cis-2-methylcyclohexene
minor amt B
mainly A
H
OH2
CH3
minor conformer
H
H
H
H
OH2
CH3
OH2
H
H
H
H
H
H
H
H
major conformer
CH3
minor conformer
O
trans-2-methylcyclohexene
B
O
P(OH)2
Trans-2-methylcyclohexanol can react by an
E2 mechanism only through its minor chair
conformer, which leads only to product B.
CH3
CH3
H3PO4
– H2O
OH
mixture of cis
and trans isomers
4-methylcyclohexanol
D
4-methylcyclohexanol would be expected to
produce 4-methylcyclohexene (D) with
either the E2 or E1 mechanisms.
If 4-methylcyclohexanol reacts via an E1
mechanism, are there any other alkene
products that would be expected?
A series of 1,2-hydride shifts can lead to
other carbocation intermediates.
CH3
CH3
CH3
CH3
1,2-H
shift
1,2-H
shift
H
OH2
H
H
In addition to D, it is possible to form
alkenes A and B and possibly, a trace
amount of C.
CH3
CH3
+
+
A
CH2
B
C
If A and B form from 4methylcyclohexanol, what does that tell you
about the reaction mechanism?
CH3
CH3
+
+
H3PO4
– H2O
OH
mixture of cis
and trans isomers
4-methylcyclohexanol
A
CH3
CH3
B
D
If both the E2 and E1 mechanisms are
operating in this reaction, can we say
something about the relative magnitude of
the rate constants, k1 and k2?
Reaction rate = k1[ROH] + k2[ROH][H3PO4]
Working with a partner, your job will be to
verify the existence of the Evelyn Effect for
the dehydration of 2-methylcyclohexanol
(mixture of cis and trans isomers) and to see
if a similar effect occurs with 4methylcyclohexanol (mixture of cis and
trans isomers). Propose a mechanistic
hypothesis to explain your results and
speculate about some possible causes of the
Evelyn Effect.
The lower boiling points of the alkene products relative to the alcohols,
makes it possible to distill over an alkene/water mixture as they form.
The still-head temperature during the
distillation will be lower than the bp of the
pure alkenes. Collect about 8 mL in a
graduated cylinder for the first fraction and
about 6 mL for the second fraction.
Watch the still-head temperature carefully
and stop the distillation when it starts to
drop or the liquid in your distilling flask is
low. If the liquid completely distills and
you see foaming and white fumes, remove
the heat source from your distilling flask
before it forms a black tar that is difficult to
remove from the flask.
Chem 309 - Exp 21
As you know, much of each grade for the experiments in this course depends
on the quality o f your discussion sections, which should always be clear and
concise. The discussion section for Exp 21 is the most challenging of the
semester, and will count for 30 out of the 55 point s. Refer to the book, and
your lecture notes for detailed mechanisms, and remember the following:
 You will work in pairs: each individu al will p erform one acid-catalyzed
dehydration reaction . One member of each pair will use 2methylcyclohex anol as the starting compound, and the other will use 4methylcyclohex anol. Each pair must then analyze the results of BO TH
reactions together by 1H- NMR and discuss their results for both
compounds.
 Each cyclohexanol is a mixture of TWO isomers: 50% cis and 50%
trans.
 There are TWO mechanisms to consider, E1 and E2.
 You and your partner will collect TWO fractions from the distillation.
Experiment 21 describes what the author calls the "Evelyn effect," which
we will define as fraction 1 and 2 having a different ratio of products.
Under the supervision of the TA, measure proton NMR spectra for each
fraction and analyze the integration areas of the vinylic protons. As
soon as you complete this NMR analysis for each fraction and compare
the % composition s, you will easily see if they are different.
The main part of your discussion is to explain the NMR results for each
cyclohexanol mixture in terms of mechanism. For each of the two starting
compounds, you must discuss the follo wing six considerations in the order
listed below. Use subheading s to separate your answers to each question
clearly.
State the percentage of 1-methylcyclohexene for each fraction .
1.
2.
3.
4.
Is there an Evelyn effect?
Is the Zaitsev rule follo wed?
Discuss possible rearrangements, and implic ation s for the mechanism
Discuss reactions of the cis vs. trans compounds, the anti-periplanar
requir ement for E2, and impli cations for the mechanism.
5. Explain the Evelyn effect, where it is observed.
6. Final conclusion: Is the mechanism E1, E2, or both?
How would you use NMR integration to calculate
relative percentages of components in a mixture?
How do you choose which hydrogens to integrate?
The integration areas of isolated hydrogens can be
used to calculate relative percentages of components
in a mixture.
Calculating Percentages using Integration areas
0.95
0.95+0.94
x 100%
=
50%
OR
1.10
1.10+0.90
x 100%
=
55%
Simulated 1H NMR spectrum of 1methylcyclohexene
H
CH3
H
H
H
H
H
6
5
4
H
H H
3
PPM
2
1
0
Simulated 1H NMR spectrum of 3methylcyclohexene
H
H
CH3
H
H
H
H
H
H H
7
6
5
4
3
PPM
2
1
0
Simulated 1H NMR spectrum of 4methylcyclohexene
H
H CH3
H
H
H
H
H
H
H
6
5
4
3
PPM
2
1
0
The second exam will be on Wednesday,
Mar. 30 and will cover experiments 4, 5, 15
and the intro to GCMS expt).
Concepts to understand:
1) ester hydrolysis
2) ester formation from a carboxylic acid
and alcohol – know the mechanisms!
3) interpretation of simple IR and mass
spectra – be able to identify important
fragment peaks in mass spectra or
stretching or bending bands in IR
spectra
4) chromatography p rinciples
a) gas chromatography
b) column chromatography
c) thin-layer chromatography