Regulation and Evaluation of Ring Closing Metathesis by Use of

Grubbs 2nd Generation Catalyst in Various Experimental Conditions

Johnathan Harvell
CHEM 440 L01
Undergraduate of Chemistry, Colorado State University, Fort Collin, CO, 80521, United States
11 December 2015
Introduction
The metathesizing of olefins have been a massive field of research for chemists over the
past few decades, and have resulted in many discoveries along the way. One discovery in
particular was made by Robert Grubbs, who theorized that a well-defined ruthenium carbene
complex would allow potential ring closing metathesis in
olefins that would have consistent percent mass recovery
yields.1 The complex soon became known as Grubbs
catalyst, and is now widely used in laboratories across the
world due to its high effectiveness of performing multiple
metathesis. The most current rendition of the Grubbs
catalyst is of the 2nd generation structure demonstrated in
Figure 1. The ruthenium carbene complex within Grubbs
catalyst is sufficiently tolerable to interactions with
functional groups present within solution, which allows for
a higher reaction selectivity by the use of this catalyst.1
Before the discovery of Grubbs catalyst, a common olefin
metathesis catalyst used was a carbene complex that had a Figure 1: GG2 Structure
molybdenum base; however, due to the range and instability of the molybdenums oxidations
states, the complex was highly likely to bond and react with functional groups, primarily
consisting of alcohols, acids and aldehydes.1 Grubbs overcame this endeavor by allowing the
ruthenium to only maintain one oxidation state within the complex by the inclusion of chloride
ions and electron acceptors such as phosphorous and nitrogen.
 For ring closing metathesis to be
performed by use of the Grubbs catalyst,
the catalyst must come in contact with

Figure 2: General RCM Mechanism Using GG2

two terminal alkene groups to allow the

formation of a new ring to occur. Due to
an excess electron pair on ruthenium and
the metals need to become octahedral, ruthenium will create a covalent bond with one of the
alkene groups, thus causing a four-membered ring intermediate to occur. With the four
membered ring being unstable and the electron affinity of ruthenium, an alkene group is released
into solution as a result. Since the released alkene group is stable in solution, it is less likely to
attack the ring and bond back into the structure. With the complex attached to the olefin, steric
hindrance allows the complex to shift towards the next terminal alkene group. A similar four-
membered ring intermediate is formed; however, the preference of stability in a closed ring
outweighs rutheniums need to be come octahedral, therefore the complex is released from the
structure and the new ring is formed. A general example of the ring closing metathesis (RCM)
mechanism using Grubbs 2nd generation catalyst (GG2) can be seen in Figure 2.
In this experiment, the mechanism of RCM using GG2 was utilized in producing diethyl
cyclopent-3-ene-1,1-dicarboxylate (DCPD) from diethyl diallylmalonate (DDM) and various
changes in procedure were made in each trial by individuals of the experimental group in regards
to age of catalyst, reaction exposure to moisture/atmosphere, and purification method. These
procedural changes and the accumulation of data from the entire experimental group was used to
help develop an optimal procedure and conditions for RCM with GG2 to produce high percent
mass recovery of purified DCPD. In Figure 3, the experimental reaction mechanism of creating
DCPD from DDM using GG2 can be seen.
Experimental Procedure1234
75 L of diethyl diallylmalonate
Figure 3: Experimental RCM of DDM using GG2
(DDM) was placed in a dry, 50 mL round
bottom flask with 20 mL of distilled dichloromethane (DCM), magnetic stir bar, capped with a
rubber septum, and allowed to stir. The flask was degassed for 30 seconds by introduction of
nitrogen gas from a filled balloon attached to a syringe that was injected into the flask via the
rubber septum while using another small syringe needle to maintain an inert atmosphere. 0.012 g
of GG2 was added to the flask mixture with continuous stirring and degassing by the nitrogen
filled balloon. After 15 minutes, reaction was checked by TLC using a AgNO3 coated TLC plate
in a 0.03:1 ether : DCM TLC solvent solution, and spots were visualized by UV light and
KMnO4 stain. If reaction was incomplete according to TLC, the mixture was allowed to stir for
an additional 25 minutes and then rechecked for completeness by TLC. If reaction was
completed according to the TLC plate, 0.24 g of activated carbon was added to the reaction flask
and mixture was allowed to stir at room temperature for an additional 48 hours.
After stirring period was completed, the mixture was filtered into a dry, pre-weighed 50
mL round bottom flask using a fritted funnel with a 1 inch layer of celite for effective separation
of activated carbon from product. Filtrate was concentrated by rotary evaporation and a crude
yield was determined. The crude product was added to 20 mL of non-distilled DCM to prepare
for purification. The product was purified by flash column chromatography using 4 mL of silica
gel, pure hexane wash, and separation was performed by using 30 mL of 5:1 hexane : DCM
mixture. Purified product in produced fractions were isolated by TLC using 5:1 hexane : DCM
TLC solvent and silica coated TLC plates. The isolated fractions were placed in a dry, pre-
weighed 50 mL round bottom flask together and were concentrated by use rotary evaporation.
After the removal of excess solvent, a purification yield of the final product was determined and
was characterized by use of 1H-NMR using CDCl3 solvent.
For the second trial, the same procedure found in trial 1 was performed; however, before
the degassing of the initial reaction using the nitrogen filled balloon was performed, the flask
was allowed to stir without being capped by a rubber septum for ten minutes, which allowed
decent exposure of the reaction mixture to the surrounding atmosphere.
For the third trial, the same procedure found in trial 1 was performed: however, instead of
degassing the initial reaction mixture with nitrogen gas before introducing the activated carbon,
air was pumped directly into the reaction mixture via the same degassing apparatus used in trial 1
for 25 minutes.
Results
In Table 1 and 2, the retention factors of all TLC plates before introduction of the
activated carbon and after purification for each trial performed found in Appendix A can be seen
below:
Table 1: TLC Plate Retention Factors for Initial Reactions of All Trials
Trial # Spot Solute Distance Solvent Distance Retention Factor
(cm) (cm)
1 Product (P) 1.5 3.2 0.47
Co-Spot (C) 2.0 3.2 0.63
Starting (S) 2.4 3.2 0.75
2 Product 2.75 3.2 0.86
Co-Spot 2.75 3.2 0.86
Starting 2.75 3.2 0.86
 3 Product 1.4 3.2 0.44
Co-Spot 1.6 3.2 0.50
Starting 1.7 3.2 0.53

Table 2: TLC Plate Retention Factors for All Trials after Purification
Trial # Spot Solute Distance Solvent Distance Retention Factor
(cm) (cm)
1 Product (P) 2.75 5.3 0.52
1 2.75 5.3 0.52
2 Product 2.75 5.3 0.52
2 2.75 5.3 0.52
3 Product 2.20 5.3 0.42
1 2.20 5.3 0.42
2 2.20 5.3 0.42
In Table 3, the percent mass recoveries for all three trials performed in the experiment
can be seen below:
Table 3: Percent Mass Recoveries for All Experimental Trials
Trial # Pure or Experimental Theoretical Mass Percent Mass
Crude Mass (g) (g) Recovery (%)
1 Crude 0.255 0.071 259.2
Pure 0.077 0.071 108.5
2 Crude 0.273 0.071 284.5
Pure 0.194 0.071 173.2
3 Crude 0.042 0.071 59.15
Pure 0.032 0.071 45.07

In Appendix B, the experimental 1H-NMR for the purified product of trial #1 can be seen
with following spectral peaks: 7.245 ppm (s, i = 1, J = 0, K-H), 5.561 ppm (s, i = 1, J = 0, D-H),
5.262 ppm (s, i = 1, J = 0, G-H), 4.117-4.188 ppm (q, i = 37.8, J = 3, B-H), 2.967 ppm (s, i =
39.1, J = 0, C-H), 2.129 ppm (s, i = 38, J = 0, J-H), 1.184-1.232 ppm (t, E-H [1.232 ppm], A-H
[1.184-1.206 ppm], i = 63.2, J = 2), 0.811-0.932 ppm (q, i = 8.166, J = 3, F-H).
In Appendix C, the experimental 1H-NMR for the purified product of trial #2 can be seen
with the following spectral peaks: 7.245 ppm (s, i = 1, J = 0, K-H), 5.556 ppm (s, i = 7.81, J = 0,
D-H), 5.258 ppm (s, i = 4.54, J = 0, E-H), 4.035-4.184 ppm (qq, i = 29.3, J = 7.335, B-H), 2.964
ppm (s, i = 16.7, J = 0, C-H), 2.123 ppm (s, i = 39.9, J = 0, J-H), 1.995 ppm (s, i = 15.9, J = 0, M-
H), 1.180-1.234 ppm (dt, A-H [1.180-1.204 ppm], F-H [1.210-1.234 ppm], i = 68.6, J = 5.885),
0.783-0.856 ppm (q, i = 24.5, J = 3, G-H)
 In Appendix D, the experimental 1H-NMR for the purified product of trial #3 can be seen
with the following spectral peaks: 7.246 ppm (s, i = 0.153, J = 0, K-H), 5.563 ppm (s, i = 1, J =
0, D-H), 5.268 ppm (s, i = 1.38, J = 0, E-H), 4.125-4.196 ppm (q, i = 2.64, J = 3, B-H), 2.977
ppm (s, i = 2.63, J = 0, C-H), 2.135 ppm (s, i = 4.26, J = 0, J-H), 1.193-1.240 ppm (t, F-H [1.240
ppm], A-H [1.193-1.216 ppm], i = 7.63, J = 0), 0.797-0.869 ppm (q, i = 3.3, J = 0, G-H).
Discussion
In Table 1-2 and Appendix A, it can be found that some of the product (P) spots travelled
the exact same distance as the starting material (S) spots on both the AgNO3 and silica based
TLC plates. With this observation, it can be inferred that not all of the starting material was
consumed by the introduced GG2 and converted to the DCPD before catalyst quenching with the
activated carbon. This inclusion of starting material could allow further impurities to be present
in the 1H-NMR spectrums found in Appendices B-D; an example of a possible impurity can be
found at approximately 1.2 ppm and 4.2 ppm of each spectrum, which can relate to the hydrogen
atoms found on both terminal ether groups in both DDM and DCPD. Due to this overlap in
chemical shift, it is possible that the integration number present at these particular spectral peaks
can be demonstrating the presence of both DDM and DCPD. This impurity would cause similar
error in the calculated percent mass recovery values presented in Table 3. With the additional
mass of the reactant, both calculated yields would be larger in value and would provide error to
the actual mass of the purified DCPD obtained in the experiment. Since DCPD and DDM
reactant have similar structures, it can be inferred that both would be separated from GG2 during
flash column chromatography, but not to an extent to where both are separated from each other.
To obtain more accurate percent mass recovery values, the experiment would need to be
performed again by either an alternate or additional purification technique to allow DDM and
DCPD to be separated. This procedural change would help lower the amount of error in percent
mass recoveries and 1H-NMR inferences.
As seen in Table 3, trial #3 was the only trial to have a loss of yield in purified DCPD
throughout the experiment. Some reasons of this loss can be attributed to the separations
performed through the experiment by both filtration and flash column chromatography. If celite
layer was too deep during initial filtration of the activated carbon, it is possible that some DCPD
may have been kept in the funnel instead of traveling through the reaction flask. Another
possibility is the incorrect isolation of fractions containing purified product or left over DCPD in
column upon performing flash column chromatography. If TLC plates were misread at the time
of identifying DCPD, it is quite possible that some purified product was tossed out with the
waste. If the column was not packed tight enough, it is possible that some of the purified DCPD
could be left in suspension in the silica gel, which would allow some purified DCPD to not make
it to the fractions that were accumulated in the experiment and not be included in the calculations
of percent mass recoveries.
In Appendices B-D, it can be found that spectral peaks J-H (2.13 ppm) and M-H (2.00
ppm) might possibly correlate to the presence of GG2 in the purified product based on the
predicted chemical shifts of certain phenyl group hydrogens found on each ruthenium ligand;
however, it is possible that these peaks could be attributed to the presence of other un-extracted
solvents, such as acetone and CDCl3. For example, acetone has a predicted shift of 2.13 ppm for
each terminal methyl group, which is exactly the same as the peak that is associated with J-H in
Appendices B-D. The presence of acetone could explain why the integration number of the
spectral peaks found at 2.13 ppm are much higher in value and intensity than some of the other
spectral peaks found in each spectrum of Appendices B-D. For the M-H spectral peaks found at
2.00 ppm, no identified reagent could be determined based on the data obtained; however, the
phosphorus phenyl groups on GG2 have predicted chemical shifts ranging from 1.6-2.0 ppm,
thus could be a source of intense M-H spectral peak at 2.00 ppm in Appendix C and D.
In the comparison of experimental data in Appendices B-D to the provided 1H-NMR
spectrums in Appendices E and G, it can be seen that a similar pattern of spectral peaks occur at
peaks of 3.00 ppm and 4.2 ppm due to the similar integration and multiplicity, which can to
related to the presence of DCPD. In Appendix G, a E-H triplet peak at approximately 1.3 ppm
can be seen and be attributed to both the presence of DCPD and DDM in the purified product in
Appendix B-D; however, due to the use of hexanes in purification, it is possible that A-H, E-H,
and F-H found at 1.3 ppm in Appendices B-D only pertain to the presence of excess hexane in
the purified product, or the combination of both hexane and DDM. Since there are no similar
peaks of DDM in both chemical shift and multiplicity found in Appendix G that can be found in
the spectrums of Appendices B-D other than the peak at 2.3 ppm, it can be further inferred that
there is a possibility that no starting material remains in the purified product, and the present
impurities can be attributed to excess solvents that were not separated from solution by both
flash chromatography and rotary evaporation.
With the provided 13C-NMR spectrums in Appendices H and F, it is to be noticed that
there are only seven spectral peaks in the spectrum of Appendix F, while there are eight spectral
peaks in the spectrum of Appendix H. This observation infers that the DCPD product allows for
the presence of one more carbon environment that is not present DDM; due to the ring closing
metathesis of the pentene ring of DDM starting material, an additional carbon environment is
created by the alkene bond of the newly created pentene ring, which is responsible for the
presence of the additional spectral peak at 118.83 ppm in Appendix H and is not seen in
Appendix F.
In Appendix I, the variables evaluated by the team members of the experiment group did
indeed result in a variety of somewhat conflicting data, which could be attributed to the
performance of techniques, contamination, and other sources of error that were present at the
time each team member performed the experiment. With the provided data found in Appendix I,
it was concluded that the following changes could be made to the procedure to optimize percent
mass recovery in the experiment: using non-distilled DCM instead of distilled DCM, using
freshly made GG2, and utilizing recrystallization with ether/hexane along with flash column
chromatography.
With the data presented by Jacob and April in Appendix I, it can be inferred that non-
distilled DCM still yields the same amount of DCPD as distilled DCM, which allows the reaction
to be of low cost and infers that the reaction has low reactivity to the presence of moisture in
solution; however, based on the data presented by Angel, it appears to have the reverse effect on
the solution, which is further validated by the impurity associated with the non-degassing of the
reaction mixture due to the presence of moisture in the atmosphere. In correspondence with the
data obtained in this set of trials, as seen in Table 3, the percent mass recovery values for both
intervals of time that the reaction was exposed to the atmosphere were higher than 100%, which
insinuates that impurities were present and could be possibly attributed from over exposure of
the reaction mixture to moisture in the air. Due to waters high polarity and ability to form
hydrogen bonds, it is possible that water could form complexes with both DDM, DCPD and
GG2 within the reaction mixture causing a hindrance in equilibrium, thus allowing either other
complexes to be formed in solution or the ceasing product formation. With this, it was concluded
that non-distilled DCM can help optimize the reaction in regards to cost, but would still maintain
a constant percent mass recovery as demonstrated in the trials by Jacob and April; however,
degassing of the reaction mixture is still relevant and needs to be performed due to exposure in
the moisture in atmosphere can lead to further impurities and error in data as demonstrated by
data obtained and presented by Angel in Appendix I.
In regards to the age of the catalyst, various observations of the catalysts reactivity in
solution were made by Suryia, David, Kaylen, and Katrina and can be seen in Appendix I. The
most relevant data is present in Katrina and Davids data, which indicates that the 2014 GG2
catalyst had higher reaction yields and less impurities in the final product. With this observation,
it can be inferred that a freshly made GG2 catalyst will have the same reaction productivity or
even better, thus it is concluded that freshly made GG2 catalyst can be used to optimize the
reactions. This is primarily based on the assumption that the selectivity of the ruthenium base
degrades over time and the oxidation state of the metal become harder to control due to the
exposure of the catalyst to oxygen. If the ruthenium base loses its preferred oxidation state, it is
more likely to bond with other functional groups in solution and prevent the production of the
needed product.
For purification, as stated earlier, it is to be noticed that DDM and DCPD cannot be
separated by just flash column chromatography; however, with recrystallization by use of
ether/hexane as demonstrated by Lindsi in Appendix, the final product can be further purified by
removal of any excess solvents and possibly excess DDM. This observation of further
purification of the final product can be attributed to the choice in utilizing ether for
recrystallization. Since both DCM and DCPD have terminal ether groups within their structures,
the two compounds are more likely to achieve a higher solubility in the ether/hexane solution.
With the two soluble in solution, excess solvents can be evaporated out of solution during the
heat process; however, to separate DDM and DCPD in recrystallization, DCPD would need to
have lower solubility than DDM and need to be filtrated out of the recrystallized solution before
DDM precipitated. In this observation, it is concluded that flash column chromatography should
be performed first to remove any excess catalyst and then recrystallized by ether/hexane to
remove any excess solvent and DDM to help optimize the percent mass recovery of purified
DCPD.
The purpose of this experiment was to demonstrate and observe a ring closing metathesis
produced by the introduction of Robert Grubbs 2nd generation ruthenium based catalyst and
evaluate the various effects on that reaction that may be associated with environmental factors or
techniques performed in the experiment. As a result of the experiment, it was found that Grubbs
metathesis of DDM yielded a relatively stable, consistent percent mass recovery, but is hindered
by the presence of impurities invoked by excess solvent or reactant; to help optimize the
procedure used in this experiment, it was found that the use of fresh GG2 catalyst, non-distilled
DCM, and the introduction of a second purification by recrystallization in ether/hexane to be the
most effective based on the data provided by the rest of the experimental group through the trials
that they performed.
References
(1) Fu, G.C.; Nguyen, S.T.; Grubbs, R.H.; J. Am. Chem. Soc., 1993, 115, 9856.
(2) Schepmann, H.G., Mynderese, M.; Journal of Chemical Education, 2010, 87, 721-723.
(3) Cho, J.H.; Kim, B.M.; Organic Letters, 2003, 5, 531-533.
(4) Ahn, Y.M., Yang, K., Georg, G.I.; Organic Letters, 2001, 3, 1411-1413.

Appendix A: TLC Plates of Trial 1-3 Reactions and Purification

Trial 1:

Before Introduction of Activated Carbon After Flash Column Chromatography

Trial 2:
 Before Introduction of Activated Carbon After Flash Column Chromatography

Trial 3:

Before Introduction of Activated Carbon After Flash Column Chromatography

Appendix B: 1H-NMR Spectrum of Trial # 1 Reactions and Separations
Appendix C: 1H-NMR Spectrum for Trial # 2 Reactions and Separations
Appendix D: 1H-NMR Spectrum for Trial # 3 Reactions and Separations
Appendix I: Comprehensive Variable Data Obtained by Team Member Trials
 Variable Team Procedural Impurities Theoretical Product
Member Change Present? Product Amount
Found? Relative
to Trial
#1
Age of Catalyst Suriya 2012 GG2 Yes Yes Constant
2014 GG2 Yes Yes Constant
Purification Jessica Recrystallization Yes Yes Constant
Method w/ Hexanes and
Ethyl Acetate
TEA as Catalyst Yes Yes Constant
Quencher
Reaction Exposure to Angel Non-Distilled Yes Yes Constant
Moisture/Atmosphere DCM / No
Degassing
Non-Distilled Yes Yes Constant
DCM / No
Degassing / 1
mL H2O Added
Purification Method Lindsi Recrystallization No Yes Constant
w/ Ether and
Hexanes
Acetonitrile as Yes Yes Low,
Catalyst catalyst
Quencher no
quenched
Age of Catalyst David 2014 GG2 Yes Yes High
2013 GG2 Yes Yes High
Reaction Exposure to April Non-Distilled No Yes Constant
Moisture/Atmosphere DCM
No Degassing No Yes Constant
Age of Catalyst Katrina 2014 GG2 No Yes Constant
2012 GG2 No Yes Constant
Age of Catalyst Kaylen 2014 GG2 Yes No Low
2012 GG2 Yes Yes Constant
Purification Method Tyler and Recrystallization Yes Yes Low
Mohammad w/ Ethyl Acetate
DMSO as Yes Yes Low
Catalyst
Quencher
Reaction Exposure to Jacob Non-Distilled No Yes Constant
Moisture/Atmosphere DCM
No Degassing Yes Yes Low