Nucleophilic Addition on α,β-unsaturated carbonyl compounds
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Transcript of Nucleophilic Addition on α,β-unsaturated carbonyl compounds
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Nucleophilic Addition on α,β-unsaturated carbonyl compounds
How it is carried out and the investigation on how different reactants would affect the reaction
Esther Ho
Gownboys
Supervisor: Dr. O W Choroba
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Contents
Abstract P.3
Introduction P.3-7
1. Lewis Acid and Base, HSAB : Nucleophiles – Thiols and Grignard Reagents
2. α,β-unsaturated carbonyl compounds and nucleophile addition with these compounds
3. Conjugation Addition and Michael Addition
Experimental Part P.8-10
Results P.10-11
Discussion P.12-17
Conclusion P.17-18
Appendix P.19-33
I. Butenone + Thiol Reaction GCMS II. Phenyl Butenone + Thiol Reaction GCMS III. Pentenone + Thiol Reaction GCMS IV. Methyl Hexenone + thiol reaction GCMS V. Acrylamide + Thiol Reaction GCMS VI. Acryloyl Chloride + Thiol Reaction GCMS VII. Butenone + Grignard Reaction GCMS VIII. Predicted NMR for Butenone + Thiol Reaction IX. Actual NMR for Butenone + Thiol Reaction
Bibliography P.34
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Abstract
Michael Reaction is a very useful reaction in organic chemistry where it forms useful c-c bonds.
Ultimately a Michael Reaction is a conjugate addition where a nucleophile attacks a C=C double
bond on a α,β-unsaturated carbonyl compounds rather than carrying out what is normally expected, a
1,2-direct addition to the C=O bond. An experiment was carried out to investigate how different
nucleophiles, in this case, a thiol and a Grignard reagent, would affect how the reaction is carried
out. Different α,β-unsaturated carbonyl compounds are also used to investigate how different factors
affect the reaction, including steric hindrance and electron donating properties of different groups. In
the experiment, 3-buten-2-one, 3-penten-2-one and 5-methyl-3-hexen-2-one reacted with the thiol
carrying out a 1,4-addition, while a reaction between 3-buten-2-one and the Grignard reagent gives a
double addition product.
Introduction
1) Lewis Acid and Base, HSAB : Nucleophiles – Thiols and Grignard Reagents
A). Lewis Acid Base Theory and the HSAB Concept
Proposed by Johanness Nicolaus Brønsted and Thomas Martin Lowry in 1923, Brønsted–
Lowry acid–base theory is probably the most well known acid-base theory where it defines acid as a
proton donor, and base as a proton acceptor. However, a more general definition of acids and bases
was proposed by Gilbert Lewis in the same year, where a Lewis Acid is defined as an electron pair
acceptor and a Lewis base as an electron pair donor. A Lewis Acid-Base reaction combines orbitals
to stabilize the pair of electrons.1
Feeling that there is a need to unify inorganic and organic chemistry, Ralph Pearson introduced
the Hard and Soft (Lewis) Acid Base Theory (HSAB Theory/ Pearson Acid Base Concept) in the
early 1960s.2 This theory defines Acids and Bases further, by classifying the Lewis Acids and Bases
further into hard/soft acids or bases. Hard acids form stronger bonds with hard bases, while soft
acids form stronger bonds with soft bases. This can be summarized by hard-likes-hard and soft-likes-
soft. Hard acids have high positive charge and high energy LUMO (Lowest Unoccupied Molecular
Orbitals) while hard bases have high negative charge and low energy HOMO (Highest Occupied
Molecular Orbitals), hence they are able to form a stronger ionic bond. HOMO of the hard acid and
LUMO of the hard base are far apart in energy, so they form an ionic bond with little overlapping of
the orbitals. 3
In contrast, soft acids and bases are bigger ions and molecules. Their orbitals are closer in
energy, and are of higher-energy and more diffused. Hard species are small and hence have little
space for charge diffusions, and they have no means of stabilization. Soft species on the other hand,
have diffused charges (a more diffused charge leads to higher softness), where the charge gets to
spread out more due to large space or resonance. 4
1 Solomons, T.W.Graham: Organic Chemistry, 7th Edition, Wiley, 2000
2 www.wikipedia.com/wiki/HSAB_theory, accessed 17th July 3 Fleming: Molecular Orbitals and Organic Chemical Reactions, student edition, Wiley, 2009 4 www2.trincoll.edu/~tmitzel/chem211fold/classnotes/1126_mon/1126_mon.htm, accessed 24th July
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There is no pure softness or hardness, because bond strength comes from both types of
interactions. So while a reaction between soft bases and acids would dominantly be due to orbitals
overlapping, there would still be a bit of electrostatic attractions between charges.
B). Nucleophiles
Nucleophile means a nucleus-loving species. It is a negatively polarized, electron-rich atom
which forms bond by donating a pair of electrons to a positively polarized, electon-deficient atom. A
nucleophile can be either neutral or negatively charged. As a Lewis Base is defined as an electron
pair donor, by definition, nucleophiles are Lewis bases.
Although nucleophiles are referred as Lewis Bases, nucleophilicity does not necessarily equal
to basicity. Basicity measures the position of equilibrium, while nucleophilicity is measured by the
relative rate of reaction. For example, hydroxide ion is a stronger base than cyanide ion since it has a
greater affinity for a proton, where for is nearly 16, while HCN is near 10, but cyanide ion
is a stronger nucleophile where it reacts more rapidly with an electrophile than hydroxide ion. 5
C). Thiols
Thiols are sulphur analogs of alcohols, where the –SH group is referred to as mercapto, from
the latin word mercurium (“mercury” in english), and captare (“to capture”), because of its ability to
precipitate mercury and other heavy metal ions.6 They have a characteristic appalling odor, where
the smell of one part of ethanethiol in fifty-billion parts of air can be detected by the average human
nose.
While oxyanions are small, highly-charged and have low-energy filled orbitals that they are
classified as hard, thiols are much larger and have high-energy filled orbitals.7 They are hence
classified as soft, and would prefer to attack saturated carbon atoms. Iodide ion is one of the softest
bases because of its size, where it has an absolute hardness ( of 7.4 eV, while thiol ( has
of 8.1eV, which is comparatively very soft comparing to hydroxide ion that has of 12eV. 8
Thiols are among the best nucleophiles to carry out a conjugate addition. As stated in section
1A, attractions between electrophiles and nucleophiles are due to the electrostatic attraction between
positive and negative charges, and orbital overlap between HOMO of the nucleophile and the LUMO
of the electrophile. Whereas the hard acids and bases would dominantly have the electrostatic
attractions, the attraction between soft acids and bases would be the overlap of orbitals. As thiols are
very soft, they are very capable of attacking the also soft C=C site, which makes the conjugate
addition possible to carry out.
D). Grignard Reagents
Grignard reagents are one kind of organometallic reagents, where they are organomagnesium
halides. They are very strong lewis bases, which are capable to combine with weak acids like water
easily. They are also very strong nucleophiles to add to carbonyl compounds. The C=O in carbonyl
compounds are reactive because of the polarization, where the Oxygen is electronegative and leaving
carbon to be partially positive. The carbon is hence able to undergo nucleophilic attack.
5 Fleming: Molecular Orbitals and Organic Chemical Reactions, student edition, Wiley, 2009 6 McMurry: Organic Chemistry, 5th Edition, Brooks/Cole, 2000 7 Clayden,Greeves,Wareen,Wothers: Organic Chemistry, Oxford, 2001 8 Fleming: Molecular Orbitals and Organic Chemical Reactions, student edition, Wiley, 2009
5
The C-Mg bond is polarized as the Magnesium is less electronegative than Carbon. The C-
Mg bond is hence polarized towards the carbon, and the carbon would then attack electrophile as it
is partially positive.
2) α,β-unsaturated carbonyl compounds and nucleophile addition with these compounds
α,β-unsaturated carbonyl compounds are ketones or aldehydes that have a double bond
conjugated with a carbonyl group. The α carbon refers to the carbon atom next to the carbonyl, and
the next carbon is the β carbon.
Normally, an alkene will react with electrophiles because C=C is electron rich and will donate
electron pairs to electrophiles. However with the C=O that gives a conjugated molecule, the
electrons are delocalized over the C=C carbons and the C=O.
As the two double bonds lie in the same geometric plane, the p-orbitals of the two double bond
systems are aligned. These compounds are therefore stabilized by resonance, resulting in the
delocalization of the partial positive charge on the carbonyl carbon.
The carbonyl carbon is hybridized, and forms both a bond and a p bond to
oxygen.9 Since the oxygen is highly electronegative, the carbonyl group is strongly polarized. The
electronegative oxygen atom of the carbonyl withdraws electrons from the β carbon, making the β
carbon more electron-deficient and electrophilic than a normal alkene. The C=C double bond is
therefore relatively electron poor.
Figure 1 and 2 are electrostatic potential diagrams of a ketone and a diene respectively.10
Figure 1 is of 3-butenone (which is a classic Michael Acceptor and is used in the experiment) while
figure 2 is 1,3-butadiene that has two C=C bonds.
The red region in figure 1 shows the high electron density at the O of the C=O bond, and the
blue regions of the lower electron density of the conjugated C=C. Comparatively, the C=C in figure
2 is much more electron-rich.
α,β-unsaturated carbonyl compounds can react with nucleophilic reagents in two different
manners. The first kind is a simple 1,2-addition, where the nucleophile is added across the C=O
bond. The C=O bond is the only bond that takes part in the reaction. The second kind is a
9 McMurry: Organic Chemistry, 5th Edition, Brooks/Cole, 2000 10 diagrams from : http://www.mhhe.com/physsci/chemistry/carey/student/olc/graphics/carey04oc/ref/ch18reactionconjugated.html,
accessed 20th July 2011
Figure 1 Figure 2
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conjugate 1,4-addition, where the nucleophile attacks the end of the conjugated system at the end of
the C=C bond. Both the C=C and C=O bonds take part in this reaction.
3) Conjugate Addition and Michael Addition
The simple addition gives a kinetic product where the reaction proceeds faster but the product
is less stable. The simple addition would proceed faster because although the β carries some positive
charge, the α carbon carries even more (since it is directly bonded to the Oxygen) and so the
electrostatic attraction would encourage the nucleophiles to attack the carbonyl group directly,
instead of attacking the C=C to carry out a conjugate addition. However, the conjugate addition in
contrast gives a more stable compound, where the product is thermodynamically favored. Initially,
the product of a conjugate addition is a resonance-stabilized enolate ion, and it undergoes
protonation on the α carbon to give a saturated ketone or aldehyde.11
After the protonation, the net
effect of the reaction is an addition of the nucleophile to the C=C bond, with the carbonyl group kept
unchanged. Since the strong C=O bond is retained, the product is more stable than the product in a
simple addition where the strong bond is no longer kept. Although the carbonyl group seems to be
unaffected in a conjugate addition, it is crucial to the reaction since the C=C would not be activated
for a nucleophilic addition without the carbonyl group. Generally, the electron-rich C=C bond will
react with electrophiles in addition reaction, instead of carrying out a nucleophilic addition. The
MO of the C=C bond is higher in energy than the of the C=O bond, meaning that the energy is
poor (larger gap) between the C=C and the HOMO of any attacking nucleophile.12
Therefore the
interaction will be weak.
11 McMurry: Organic Chemistry, 5th Edition, Brooks/Cole, 2000 12 Fleming: Molecular Orbitals and Organic Chemical Reactions, student edition, Wiley, 2009
Figure 3 and 4 show the resonance structure of α,β-unsaturated carbonyl compounds. Due to the resonance, the β carbon and the carbonyl carbon both carry a partially positive charge, making a nucleophilic attack possible at these two sites.
Figure 3
Figure 4
7
Defined by and named after American Organic Chemist Arthur Michael, a Michael Addition
is when a nucleophile enolate anion (which can be produced from a conjugate addition) is added to
the β carbon of a α,β-unsaturated carbonyl compound.13
Although it is specified that a Michael
Reaction must involve a enolate ion acting as the Michael donor, a nucleophile can also be called as
a Michael donor, where the reaction will be called as an “Michael-Type Addition”. 14
Hence, a 1,4-
conjugate addition can also be called as a Michael-Type Addition although more precisely Michael
Addition is a specific of the 1,4-addition.
Whether a 1,2-addition or a 1,4-addition carried out depends on 3 different factors. The
conditions of the reaction, the nature of the α,β-unsaturated carbonyl compounds and the type of
nucleophile. 15
Hydroxide, cyanide, hydride and alkyllithium reagents are strong bases that would attack the
carbonyl group. They are all hard bases that would prefer to add to the hard C=O group.16
The
carbonyl carbon has a partial positive charge while the nucleophile is negatively charged. They are
attracted towards each other electrostatically, and the bonds would eventually be broken and formed
due to a favorable lowering in energy.
In the experiment carried out, how the nature of the compounds would affect the reaction was
investigated, by having different groups attached to the C=O and the C=C. How the type of
nucleophile affects the reaction was also examined by having two different nucleophiles, Benzyl
Mercaptan (C6H5-CH2-SH, a thiol) and Methyl-Magnesium Bromide (CH3-MgBr, a Grignard
reagent) and both were used to react against Butenone, which is a typical Michael Acceptor.
Some common Michael Acceptors include Propenal, But-3-en-2one, Ethyl Propenoate
because they have comparatively unreactive C=O group and a small group at the β carbon, making
the C=C electron-deficient enough to be attacked by nucleophiles to undergo a 1,4-addition.
13 http://en.wikipedia.org/wiki/Michael_reaction, accessed 20th July 2011 14 Mather, Viswanathan, Miller, Long: Michael addition reaction in macromolecular design for emerging techcnologies, 2006 15 Clayden,Greeves,Wareen,Wothers: Organic Chemistry, Oxford, 2001 16 Maitland Jones Jr.: Organic Chemistry, 3rd Edition, W.W.Norton, 1997
Figure 5 (a) and (b)
Figure 5(a) and (b) shows how the nucleophilc would attack the carbon in 1,2 and 1,4-direction respectively.
8
Experimental Part
1). Materials
Michael Acceptors Used
1. 3-buten-2-one (99%, Sigma-Aldrich) 2. 4-phenyl-3-buten-2-one (trans-4-phenyl-3-buten-2-one, ≥99%, Sigma-Aldrich) 3. 3-penten-2-one (70%, Sigma-Aldrich) 4. 5-methyl-3-hexen-2-one (technical grade, 80%, Sigma-Aldrich) 5. Acrylamide (≥99% (HPLC), powder, Sigma-Aldrich) 6. Acryloyl Chloride (97%, contains <210 ppm MEHQ as stabilizer, Sigma-Aldrich)
Michael Donors Used
- Benzyl Mercaptan (99%, Sigma-Aldrich)
- MethylMagnesium bromide (1.0M in dibutyl ether, Sigma-Aldirch )
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2). Experimental Procedure
Preparations of the Samples
1. 1.25g of Benzyl Mercaptan (molecular weight: 124.2g) was dissolved in 50 of methanol
to give a Benzyl Mercaptan Solution in methanol of 0.2M.
2. 3-Buten-2-one (70.09g), 4-phenyl-3-buten-2-one (146.19g), Acryl Amide(71.08g), Acryloyl
Chloride(90.51g) had all been dissolved in 50 of methanol to make up solutions of 0.1M.
3. The original 3-penten-2-one (84.12g) used was of 70% purity. Therefore, including the 70%,
0.6g of the original was used to dissolve in 50 of methanol to make up a solution of
0.1M.
4. The original 5-methyl-3-hexen-2-one (112.17g) used was of 80% purity. Including the 80%,
0.7g was used to dissolve in 50 of methanol to make up a solution of 0.1M.
Reaction
1. Thiol Reaction
For the GCMS:
5 of the 0.2M Benzyl Mercaptan was added with 10 of each 0.1M Michael Acceptor.
(mole ratio = 1:1). The mixture was stirred for 60 minutes, and the temperature was initially
20 and increased up to 70 during the process.
For the NMR:
Only the Buten-2-one and thiol reaction product was scanned through the NMR.
5 of the 0.2M Benzyl Mercaptan was added with 10 of the Buten-2-one. Because the
boiling point of the buten-2-one is 34 , the mixture was not heated up.
After 60 minutes, a TCL was taken (using 8 of hexane, and 2 of ethyl acetate) and
shows that all butenone has been used up. The methanol was then distilled out. The product
was then being run through a column using hexane : ethyl acetate ratio of 4:1.
2. Grignard Reaction
3-buten-2-one and 4-phenyl-3-buten-2-one were the only two compounds that were used to
react with MethylMagnesium Bromide.
20 of ether were added with around 7 of MethylMagnesium Bromide and 10 of
the Michael Acceptors. The mixture was then stirred, and gas was evolved. (which should be
Methane.) Seperating funnel was then used to extract the product, ether was used because it
would easily evaporate. Oxygen bump was then used to bump off the ether and give a pure
product.
Some of the product was then dissolved in ethyl acetate, and some was dissolved in ether.
10
3). Instruments Used
TLC Plate:
- DC – Fertigplatten SIL G-25 Pre-Coated TLC Plates, plaques fimines CCM
GCMS:
- ThermoQuest Trace GC-MS, Electron Ionisation Mode.
- Initial Starting Temperature: for 4 minutes, then the temperature was increased at a rate
of 20 /minute, until the temperature reaches 240 , where it was held for 6 minutes and the
total running time is 20 minutes.
- The Samples were injected splitless, at a volume of 1 , where the Column is of Stabilwax
and of 30m x 0.25mm (0.25 film thickness)
- All data was acquired in a full scan mode, where mass ranges from 20-500 m/z. Some data
was with a 5-minute solvent delay, and was analysed using Thermo Xcalibur.
- All samples were diluted by a factor of 100, so sample concentration was 10 .
NMR:
- Brucker 400MHz NMR, Solvent used was CDCl3 (deuteriated chloroform)
Results
Michael Acceptor R1 R2 Reaction with
Thiol (yield %)
Reaction
with
Grignard
Buten-2-one H CH3 ✓ (82%) ✓ 4-Phenyl-3-buten-
2-one
C6H5 CH3 ✗ NA
3-penten-2-one CH3 CH3 ✓ (44%) NA
5-methyl-3-hexen-
2-one
C3H7 CH3 ✓ ( 40%) NA
Acrylamide H NH2 ✗ NA
Acryloyl Chloride H Cl ✗ NA
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1). Butenone + thiol Reaction A). NMR
Protons
A 2.06
B 2.59
C 2.59
D 3.68
E 7.17-7.27
B). GCMS
Pale yellow oil. Peak at 15.34minutes (over a 20minutes period), m/z 194 ], 77[C6H5],
91[C6H5CH2], 123[C6H5CH2S], 137[C6H5CH2SCH2],151[C6H5CH2S(CH2)2]. Yield calculated by
MA=82%.
2). Phenyl Butenone + Thiol
No desirable peak observed for GCMS.
3). Pentenone + Thiol
GCMS: Peak at 14.81 minutes, m/z 208 [ ],77[C6H5], 91[C6H5CH2],
123[C6H5CH2S],135[C6H5CH2SC], 150[C6H5CH2SCCH3]. Yield calculated by MA is 44%.
4). Methyl-Hexenone + Thiol
GCMS: Peak at 15.12 minutes, m/z 236 [ ], 91[C6H5CH2], 123[C6H5CH2S],178
[C6H5CH2SCC3H7], 193[C6H5CH2SCHC3H7CH2]. Yield calculated by MA is around 40%.
5). Acrylamide + Thiol
No desirable peak observed for GCMS.
6). Acryloyl Chloride + Thiol
No desirable peak observed for GCMS.
7). Butenone + Grignard
GCMS: Peak at 7.46minutes, m/z 102 [ ], 29 [H2CCH3], 43[H2CCH3CH2], 55[H2CCH3CH2C],
87[H2CCH3CH2COCH3].
Carbons
A 29.9
B 206.7
C 43.3
D 25.2
E 36.7
F 127.0-138.2 Table 1, 1H NMR chemical shift for Benzyl Mercptan + butenone Reaction
Desired Conjugate addition Product for Benzyl Mercaptan + Butenone Reaction
Table 2, 13C NMR Chemical Shift for Benzyl Mercaptann + Butenone Reaction
12
Discussions
1). Thiol Reaction:
All Michael Acceptors used in this experiment are α,β-unsaturated carbonyl compounds that
have a double bond conjugated with a carbonyl group. The electronegative oxygen would withdraw
electron density from the β carbon and the C=C double bond is therefore more nucleophilic than
normal, hence would be able to react upon a nucleophile. Because of the Benzyl Mercaptan being a
soft nucleophile, it is therefore expected to react on the electron deficient alkene site which is also
soft. Changing the R1 changes the electron density distribution near the C=C, and would affect the
reaction being carried out because the nucleophilic thiol would only affect an electron deficient C=C,
and if the C=C gains electron density, the thiol may attack the C=O instead or there may be no
reaction.
Buten-2-one is used as a standard where the R1 is simply a Hydrogen and R2 is a methyl
group. The different R1 chosen are a methyl group, a propyl group and a phenyl group, where the
sizes are getting bigger. A bigger group is expected to be more electron donating to the C=C, making
it richer in electron density and hence reduce the probability of the nucleophile attacking.
The effect of R2 on the reaction is also examined. The R2 changes from the standard H in
buten-2-one, to NH2 in the Acrylamide and Cl in the Acryloyl Chloride. Acrylamides are usually
good Michael Acceptors as the amide makes the C=O unreactive, making C=C more reactive to act
towards soft nucleophiles and hence a 1,4-addition is expected. The Acryloyl Chloride on the other
hand, should carry out either a direct addition to the C=O bond or a nucleophile substitution where
the –Cl will be replaced. As chloride is electron withdrawing, the α carbon is made more
electrophilic and will be more able to act towards a nucleophile, making a nucleophilic
addition/substitution at the carbonyl much more possible than at the C=C site.
Buten-2-one:
3-buten-2-one is classified as an enone, where the “ene” stands for the C=C bond and the “one”
stands for ketone.17
A reaction is expected to take place because Buten-2-one itself is a good Michael Acceptor. The H
attached to the alkene does not donate much electron density, at the same time the CH3 attached to
the carbonyl does not polarize the α carbon to make it a more electrophilic site. Hence a C=O is not
favored in this compound and there is a big possibility for the thiol to attack the C=C. Because of the
thiol being a soft nucleophile, it would prefer to attack the soft C=C instead of the hard C=O.
In this experiment, buten-2-one is used as a standard, where the other Michael acceptors used is
chosen by changing either the functional group attached to the C=C bond, or the C=O bond.
17 Clayden,Greeves,Wareen,Wothers: Organic Chemistry, Oxford, 2001
Reaction between
thiol and butanone.
13
The buten-2-one is found to have reacted with the thiol as expected. The yield is around 82% under
the thiol:butenone 1:1 ratio.
4-Phenyl-3-Buten-2-one
In the 4-phenyl-3-buten-2-one, the R1 group, the group attached to the C=C is a Phenyl group.
No reaction was carried out between the thiol and the Phenyl-Butenone. With the large phenyl group,
the charges are delocalized throughout the whole compound. The C=C is no longer polar because of
the conjugation. Therefore the nucleophile was not able to attack the C=C as it is now much less
nucleophilic. There was also no addition to the C=O group as the charges are delocalized throughout
the whole compound, there was no specific electron-deficient site for a nucleophilic attack. Hence
there was no reaction at all, neither at the carbonyl or the alkene.
3-Penten-2-one
For the 3-Penten-2-one, a methyl group is now attached to the C=C instead of a H.
The reaction has carried out, and the field is 44%, under a thiol:pentenone 1:1 ratio.
Comparing with the Butenone which gives a 80% yield, the pentenone yield is much less. As the R1
group gets bigger, changing from simply a Hydrogen to a methyl group, the R1 group is now much
more electron donating and donates electron density to the C=C. The C=C is then less electron-
deficient than in the case of the butenone, and a nucleophilic attack is hence less possible. Therefore
the yield was much less than the reaction with the butenone.
5-methyl-3-hexen-2-one
A propyl group is attached to the C=C in the 5-methyl-3-hexen-2-one.
Reaction is carried out, with a yield of nearly 40% under a 1:1 mole ratio.
As the methyl group (as in the case of the pentenone) now changes to a propyl group, it is expected
that the yield would be even less the 44% in the case of the pentenone, since the R1 group is now
even bigger and would hence be even more electron donating. From the result, 5-methyl-3-hexen-2-
one and thiol reaction gives a 39% yield, where there is only a 4% yield difference comparing to the
pentenone. Although the yield calculated might not be very accurate without including calculated
errors, but it confirms the theory that a bigger R1 group would give a more electron rich C=C, which
makes the nucleophilic attack less possible, as compared with the case of the butenone. The steric
hindrance from the larger group at the β carbon also hinders attack from nucleophiles.
delocalized charges throughout the whole compound
14
Acrylamide
A NH2 amide group is attached to the C=O and a Hydrogen is attached to the C=C in the
Acrylamide.
Acrylamide is usually used as a Michael Acceptor and are available commercially.18
However, no
reaction was found to have carried out although a reaction was expected to carry out. In theory, lone
pair from the amide group would shift and form a bond with the carbonyl carbon, leaving the
oxygen negatively charged. The conjugated still exists, where the C=C are still doubly bonded and
the other double bond is the amide group with the α Carbon. Due to this conjugation, the nucleophile
would still have attacked the C=C. However no reaction was observed in the experiment. This might
be due to different reaction conditions (for example, temperature), where the condition used in the
experiment does not favor the reaction to carry out. Also, as there is another new conjugation, this
reaction might take a much longer time than the butenone reaction and not enough time was allowed
for the reaction to carry out.
18 Mather, Viswanathan, Miller, Long: Michael addition reaction in macromolecular design for emerging techcnologies, 2006
Conjugation of Acrylamide
15
Acyloyl Chloride
Reaction between acryloyl chloride and a hard nucleophile would result in a nucleophilic substitution
A Cl group is attached to the C=O and a Hydrogen is attached to the C=C in the Acryloyl Chloride.
No reaction was observed carried out. There are several reasons to explain this. Firstly, the Acryloyl
Chloride might have evaporated during the reaction of heating it up to about , where Acryloyl
Chloride has a boiling point of 75
Also, Chloride ion is a good leaving group, which might allow the thiol to substitute the chloride
instead of carrying out an addition. The thiol would have attacked the electrophilic α carbon (which
was made even more electrophilic by the electron withdrawing chloride group), where (by curly
arrows) the carbonyl bond will shift up to the oxygen, leaving a negatively charged O. As this
intermediate is unstable and chloride being a good leaving group, it would leave and the negative
charge would swing back to form back the double C=O bond. The reason that this was not carried
out might be because of the use of the nucleophile where the thiol being such a soft thiol would not
attack the hard C=O, no matter how reactive the bond is. If the nucleophile used is a hydroxide ion,
by theory it should carry out a substitution where the hydroxide would replace the chloride.
2). Grignard Reaction:
1,2-addition between Grignard Reagent and butenone
16
The Grignard Reagent used in this reaction is MeMg-Br, Methyl Magnesium Bromide. It is
expected to react with the carbonyl group because of the electronegativity of the Oxygen.
Buten-2-one was chosen to react with MethylMagnesium Bromide to compare the effect of
different nucleophiles and proving the HSAB theory. It is found to have reacted with the Grignard
reagent. However although the Grignard reagent is expected to have only reacted with the Carbonyl
group (which is a usual Grignard Reaction), it was found that a double addition has carried out and
the Grignard reagent has attacked both the C=O site and the C=C site.
To explain the double addition, it is interesting to note that another organometallic reagent,
an Organolithium reagent will react with these unsaturated carbonyl compounds exclusively in a 1,2-
addition manner, attacking the C=O site only. It is because R-Li is a hard reactive organometallic
compound as the Lithium is small and the charges are less diffused, it would prefer to add to the hard
Carbonyl carbon, hence a 1,2-addition would carry out dominantly.19
CH3MgBr, might be able to carry out a 1,4 or 1,2-addition, and might also give a mixture of
product for both reactions. The result depends on the structures of the reacting species and the
reaction conditions.20
As Magnesium is larger than Lithium, e the negative charge is able to diffuse
to Mg, making the Grignard Reagent softer than the organolithium reagent. Therefore, other than
attacking the hard C=O, the Grignard Reagent would also be able to react with the soft C=C due to
its softness. As it is still mainly hard, it would also attack the C=O, hence a intermediate between the
two additions is possible to obtain.
Interestingly enough, if Copper(I) is added to the reaction, the Grignard reagent would
undergo dominantly a 1,4-addition. The copper transmetallate the Grignard reagent to give an
organcopper reagent. Organocoppers are softer comparing to Grignard reagents, and would favor an
attack to the soft C=C bond. 21
In the experiment, a double addition has carried out where the Grignard Reagent has added
both to the C=O and the C=C, breaking both bonds.
Although only a mixture of two compounds (one where the thiol is added to the C=O and the
other one added to the C=C) is expected, it is interesting to find the double addition taken place. It
might be possible that the Grignard Reagent was adding to the C=O site first due to the hardness and
electrostatic attraction between the partial charges, but as the Grignard is in excess, it was able to add
to the C=C site as well, giving a double addition product instead of two different products. It might
also be because of the reaction condition carried out.
19 http://cnx.org/context/m15243/latest, accessed 26th July 20 Vollhardt, Schore: Organic Chemistry, Structures and Fuctions, Freeman 21 Clayden,Greeves,Wareen,Wothers: Organic Chemistry, Oxford, 2001
1,4-addition between Grignard and Butenone
17
3). Difference between the Grignard and Thiol reaction with the butenone:
The carbon atom of a carbonyl group is a hard electrophile because it carries a partial positive
charge as of the result of the polarized C=O bond. As hard nucleophiles, Grignard reagent which are
generally hard as they have a high partial charge on the nucleophilic carbon atom, and much harder
than the thiol, would be capable to react with the hard C=O bond. On the other hand, the soft thiol,
would prefer to attack the soft C=C site.
As seen from the results of the two different reactions with the butenone, thiol was obviously
added to the C=C site giving a saturated product, while the Grignard gives a double addition product.
Although the double addition product was not exactly what expected, it confirms that the Grignard
reagent which is harder than the thiol, would also attack the carbonyl, instead of just carrying out a
conjugate addition. This proves that soft-likes-soft and hard-likes-hard. The Double addition in the
case of the Grignard, may also show that a acid-base-interaction is a mixture of electrostatic
interaction and orbital overlapping, to give both the hard acid-base reaction and the soft acid-base
reaction.
4). Other Facts
Interestingly enough, the spectra of many samples give a fragment of m/z 124, which is a
dimer of the thiol. It is because thiols are easily oxidized in air to give disulfides. Hence two
hydrogens would be lost and would give a m/z of 124. During the reaction, or just maybe when the
thiols stay in air, the oxygen oxidize the thiols and give a dimer.
Conclusion
The experiment has demonstrated how different group attached to C=C or C=O respectively
would affect the reaction carried out. When a bigger group is attached to the C=C group, it would be
more electron donating towards the double bond and hence making the alkene more elctron-rich. As
the C=C becomes more electron-rich, a nucleophilic attack becomes less possible as the C=C.
Hence, the 1,4-addition would either be less possible to carry out, or would give a smaller yield. The
steric hindrance from a bigger group also discourages a nucleophilie from attacking, so if the group
attached to C=C is bigger, it is likely to give less products. This can be seen from the big percentage
difference in the reaction for the butenone and the hexenone and pentenone.
While an electron donating group at the C=C discourages the 1,4-addition, an electron
withdrawing group at the C=O, like –Cl, would encourage the 1,2-addition, as the Carbon atom
would be more partially positive and would be more favorable towards a nucleophilic attack. In fact
having a good leaving group like –Cl might actually give a nucleophilic substitution, however this
was not observed in the experiment. Also, as the amide would give another conjugation product, a
1,4-addition should have carried out but it was not observed. These unexpected results might be due
to reaction condition,where temperature and time allowed might not be favorable for these particular
reactions to carry out and hence they did not. These experiments should be carried out again in
different conditions in order to achieve the most desirable result.
The difference between the Grignard reagent and the thiol reaction with the butenone proves
the HSAB theory, where hard-likes-hard and soft-likes-soft. Being a soft nucleophile, the thiol
18
attacks the soft C=C bond, while Grignard reagent being a much harder nucleophile would attack the
C=O bond. It was interesting that Grignard reagent in fact gave a double addition product, which was
not what really expected as the Grignard was supposed to give a mixture of 1,4 and 1,2 products, or
just react in one behavior dominantly. It would be desirable if this reaction is carried out a few more
times and scanning the product through NMR to find out the structure exactly, so more can be
known about the mechanism of how the double addition was carried out.
In conclusion, it was successful to have achieved demonstrating the effects of different
groups at C=C and C=O on the reaction.
19
Appendix
Appendix I : Butenone + -SH GCMS
RT: 4.97 - 19.99
5 6 7 8 9 10 11 12 13 14 15 16 17 18 19
Time (min)
0
5
10
15
20
25
30
35
40
45
50
55
60
65
70
75
80
85
90
95
100
Re
lative
Ab
un
da
nce
RT: 15.34
MA: 420850264
RT: 11.01
MA: 175634804
NL:
6.35E7
TIC MS
9E690E8E
3A0343648
A860B646
1761252
20 40 60 80 100 120 140 160 180 200 220 240
m/z
0
10
20
30
40
50
60
70
80
90
100
0
10
20
30
40
50
60
70
80
90
100
Re
lative
Ab
un
da
nce
103.1131.1
145.1
146.1
77.1
51.143.0
102.0104.3
132.150.0147.276.063.1 138.4110.439.1 115.078.1 153.4
57.7 84.627.2 127.173.0 98.1 154.4 164.9 182.3 197.1 203.7 214.4 248.8236.1226.3
91.0
43.0123.0
194.1
65.0
124.145.0 92.1
122.0
102.039.1136.0
160.177.051.1 63.0 89.0 121.0
195.1125.171.0
27.2 79.1 196.155.0 161.193.3 137.1104.128.2 151.0 175.9 181.0 212.7 219.0 234.3 243.4
NL: 3.60E6
9E690E8E3A0343648A860B6461761
252#706-716 RT: 10.94-11.02 AV: 11
SB: 186 6.66-7.31 , 18.00-18.89 T:
{0,0} + c EI det=350.00 Full ms
[20.00-500.00]
NL: 3.88E6
9E690E8E3A0343648A860B6461761
252#1210-1234 RT: 15.16-15.36 AV:
25 SB: 187 6.66-7.31 , 18.00-18.89 T:
{0,0} + c EI det=350.00 Full ms
[20.00-500.00]
20
Appendix II: Phenyl Butenone + -SH GCMS
RT: 5.08 - 19.99
6 7 8 9 10 11 12 13 14 15 16 17 18 19
Time (min)
0
5
10
15
20
25
30
35
40
45
50
55
60
65
70
75
80
85
90
95
100
Re
lative
Ab
un
da
nce
RT: 13.32
MA: 62554118
RT: 10.59
MA: 45253482
RT: 10.01
MA: 15361530
RT: 17.70
MA: 22127953
RT: 12.85
MA: 43230316
NL:
3.37E7
TIC MS
144724790
6D541578
080825E9
C215351
20 40 60 80 100 120 140 160 180 200 220 240 260 280
m/z
0
10
20
30
40
50
60
70
80
90
100
0
10
20
30
40
50
60
70
80
90
100
Re
lative
Ab
un
da
nce
0
10
20
30
40
50
60
70
80
90
100121.1
77.0
91.075.0 122.1105.0
51.1 78.159.0 152.147.1 92.129.1 106.1 123.4 135.4 214.5179.6 194.2 241.4170.3 272.6 279.5 296.4258.3234.2
91.0
124.0
65.1
92.245.039.1
63.0 77.0125.1121.061.038.1 66.127.1 97.0 136.2 153.2 180.6166.4 259.0215.2 227.9205.6 242.5 292.2189.9 267.2
91.0
65.092.2 181.0 246.045.0 77.039.1 63.0 121.0 248.1152.997.027.1 105.0 165.0 183.3125.1 214.0 283.2207.5 219.6 289.7259.7236.2
NL: 2.21E6
1447247906D541578080825E9C215
351#591-596 RT: 9.99-10.04 AV: 6
SB: 124 8.16-8.78 , 18.57-18.98 T:
{0,0} + c EI det=350.00 Full ms
[20.00-500.00]
NL: 1.78E6
1447247906D541578080825E9C215
351#662-672 RT: 10.59-10.68 AV:
11 SB: 124 8.16-8.78 , 18.57-18.98
T: {0,0} + c EI det=350.00 Full ms
[20.00-500.00]
NL: 2.27E6
1447247906D541578080825E9C215
351#925-941 RT: 12.80-12.94 AV:
17 SB: 124 8.16-8.78 , 18.57-18.98
T: {0,0} + c EI det=350.00 Full ms
[20.00-500.00]
21
20 30 40 50 60 70 80 90 100 110 120 130 140 150 160 170 180 190
m/z
0
10
20
30
40
50
60
70
80
90
100
0
10
20
30
40
50
60
70
80
90
100
Re
lative
Ab
un
da
nce
131.0103.0
145.1
146.1
77.0
51.143.0
101.9
104.2132.1
50.0 147.276.063.039.1 78.152.0 115.091.0 117.127.1 89.038.1 133.473.0 100.9 148.644.1 105.2 155.6 181.2163.7 170.3 191.9 197.1
121.0
91.077.0
122.1
45.0 105.065.0 78.151.1 89.0 92.1 123.139.1 63.0 66.1 110.029.1 133.1 153.0145.0 165.1 178.126.1 192.4 197.1
NL: 2.04E6
1447247906D541578080825E9C215
351#983-991 RT: 13.29-13.36 AV: 9
SB: 124 8.16-8.78 , 18.57-18.98 T:
{0,0} + c EI det=350.00 Full ms
[20.00-500.00]
NL: 1.89E6
1447247906D541578080825E9C215
351#1503-1514 RT: 17.64-17.73 AV:
12 SB: 124 8.16-8.78 , 18.57-18.98 T:
{0,0} + c EI det=350.00 Full ms
[20.00-500.00]
22
Appendix III: Pentenone + -SH GCMS
RT: 5.00 - 19.95
6 7 8 9 10 11 12 13 14 15 16 17 18 19
Time (min)
0
5
10
15
20
25
30
35
40
45
50
55
60
65
70
75
80
85
90
95
100
Re
lative
Ab
un
da
nce
RT: 14.81
MA: 89589067
RT: 7.45
MA: 47406516
RT: 10.59
MA: 14154368
RT: 15.14
MA: 11389524
RT: 13.93
MA: 7132757RT: 10.01
MA: 6880822RT: 6.53
MA: 26594171
14.69
NL:
3.62E7
TIC MS
5E12C93837
784322AB03
0E52B85279
CB_0720201
1115136
20 30 40 50 60 70 80 90 100 110 120 130 140 150 160 170 180 190 200
m/z
0
20
40
60
80
100
0
20
40
60
80
100
0
20
40
60
80
100
Re
lative
Ab
un
da
nce
0
20
40
60
80
10083.0
55.1
98.143.1
39.129.169.0
27.184.153.1
56.151.138.1 99.179.126.1 67.0 89.170.1 106.0
43.1
59.1
101.1
31.1 42.1 84.069.0 86.139.1 75.027.1 60.158.044.1 102.183.0 98.1 115.1
121.0
77.0
91.075.0 122.2105.051.0 78.159.0 89.0 152.047.1 65.039.1 92.129.1 74.027.1 123.1119.0
91.0
124.0
65.092.145.039.1 63.0 77.0 89.051.1 125.1121.038.1 69.027.1 97.0 105.0 136.0
NL: 5.11E5
5E12C93837784322AB030E52B
85279CB_07202011115136#17
9-197 RT: 6.49-6.64 AV: 19 T:
{0,0} + c EI det=350.00 Full ms
[20.00-500.00]
NL: 2.35E6
5E12C93837784322AB030E52B
85279CB_07202011115136#29
2-301 RT: 7.43-7.51 AV: 10 T:
{0,0} + c EI det=350.00 Full ms
[20.00-500.00]
NL: 1.51E6
5E12C93837784322AB030E52B
85279CB_07202011115136#60
0-603 RT: 10.00-10.03 AV: 4 T:
{0,0} + c EI det=350.00 Full ms
[20.00-500.00]
NL: 1.71E6
5E12C93837784322AB030E52B
85279CB_07202011115136#66
9-675 RT: 10.58-10.63 AV: 7 T:
{0,0} + c EI det=350.00 Full ms
[20.00-500.00]
23
20 40 60 80 100 120 140 160 180 200 220 240 260
m/z
0
10
20
30
40
50
60
70
80
90
100
0
10
20
30
40
50
60
70
80
90
100
Re
lative
Ab
un
da
nce
0
10
20
30
40
50
60
70
80
90
10075.0
91.0
194.147.1 65.045.0 76.1 163.059.0 92.131.1 124.0 129.0 196.1117.099.0 226.1
91.0
43.0
123.0
117.1
65.045.0
92.2208.1
39.1124.177.0 89.0 150.059.051.0 135.0 174.1 209.227.1 100.9 165.0 181.1 190.0
91.0
43.0
122.0
123.0
124.065.045.0 99.1164.0 222.139.1 77.057.1 85.129.1 125.1100.1 120.9 149.0 166.1 179.1
NL: 1.12E6
5E12C93837784322AB030E52B
85279CB_07202011115136#106
9-1074 RT: 13.91-13.95 AV: 6 T:
{0,0} + c EI det=350.00 Full ms
[20.00-500.00]
NL: 4.46E6
5E12C93837784322AB030E52B
85279CB_07202011115136#117
5-1179 RT: 14.79-14.83 AV: 5 T:
{0,0} + c EI det=350.00 Full ms
[20.00-500.00]
NL: 9.73E5
5E12C93837784322AB030E52B
85279CB_07202011115136#121
7-1219 RT: 15.14-15.16 AV: 3 T:
{0,0} + c EI det=350.00 Full ms
[20.00-500.00]
24
Appendix IV: Methyl Hexenone + -SH GCMS
RT: 5.00 - 19.95
5 6 7 8 9 10 11 12 13 14 15 16 17 18 19
Time (min)
0
5
10
15
20
25
30
35
40
45
50
55
60
65
70
75
80
85
90
95
100
Re
lative
Ab
un
da
nce
RT: 15.12
MA: 85037762
RT: 8.48
MA: 37888556
RT: 7.73
MA: 31024453RT: 10.23
MA: 15163067
RT: 14.11
MA: 11624928
RT: 12.83
MA: 33642304
10.02
NL:
3.19E7
TIC MS
820453237
F5F4B4D9
CB187BE7
29EDFBD
20 30 40 50 60 70 80 90 100 110 120 130 140 150 160 170 180 190 200
m/z
0
20
40
60
80
100
0
20
40
60
80
100
0
20
40
60
80
100
Re
lative
Ab
un
da
nce
0
20
40
60
80
10043.1
41.1
97.169.1
112.1
39.155.127.1
53.1 79.067.1 70.129.1 98.1 113.258.1 81.050.126.1 95.1 127.1 143.1102.1 159.1138.4 197.6172.4 192.6153.3 182.3
43.1
101.0
59.155.1 87.1
41.1 71.0 129.186.1 112.129.1 45.1 69.1 97.188.183.026.1 114.1 144.1131.1 150.3 159.6 175.9170.1 192.2182.2 200.1
121.1
77.0
91.075.0 122.1105.0
51.1 78.159.0 152.195.147.139.1 65.0 89.0 117.074.029.1 127.1 187.2 199.2155.197.1 143.126.1 135.0 167.1 180.1
43.1
87.1
73.155.158.141.1 75.169.127.1 44.129.1 97.188.159.1 112.0 115.198.1 129.1 141.1 168.6146.1 176.3158.3 191.5183.2 198.3
NL: 6.05E5
820453237F5F4B4D9CB187BE729E
DFBD#324-337 RT: 7.73-7.84 AV: 14
SB: 91 5.29-5.79 , 19.42-19.66 T:
{0,0} + c EI det=350.00 Full ms
[20.00-500.00]
NL: 1.95E6
820453237F5F4B4D9CB187BE729E
DFBD#408-419 RT: 8.43-8.53 AV: 12
SB: 91 5.29-5.79 , 19.42-19.66 T:
{0,0} + c EI det=350.00 Full ms
[20.00-500.00]
NL: 1.04E6
820453237F5F4B4D9CB187BE729E
DFBD#592-602 RT: 9.98-10.07 AV:
11 SB: 91 5.29-5.79 , 19.42-19.66 T:
{0,0} + c EI det=350.00 Full ms
[20.00-500.00]
NL: 8.40E5
820453237F5F4B4D9CB187BE729E
DFBD#616-627 RT: 10.18-10.28 AV:
12 SB: 91 5.29-5.79 , 19.42-19.66 T:
{0,0} + c EI det=350.00 Full ms
[20.00-500.00]
25
40 60 80 100 120 140 160 180 200 220 240 260 280 300
m/z
0
10
20
30
40
50
60
70
80
90
100
0
10
20
30
40
50
60
70
80
90
100
Re
lative
Ab
un
da
nce
0
10
20
30
40
50
60
70
80
90
10091.1
65.092.1 181.1 246.145.0 75.0 77.039.1 63.0 121.097.0 112.1 153.0 182.9125.0 165.0 249.1194.1 213.0 225.1 266.4 286.8 297.5235.5
75.0
91.0
65.047.1 76.1 111.045.1 99.1 222.1124.031.1 137.0 145.1 165.1 191.1179.1 225.2207.1 254.1 293.6280.7269.2
91.0
43.1
145.1
123.0144.0
111.165.0
92.145.041.1 69.1
236.1146.1124.187.0 95.155.127.1 231.3178.0 237.2193.1173.3 202.1 246.4 279.1 295.7269.1
NL: 1.06E6
820453237F5F4B4D9CB187BE729E
DFBD#934-948 RT: 12.85-12.96 AV:
15 SB: 91 5.29-5.79 , 19.42-19.66 T:
{0,0} + c EI det=350.00 Full ms
[20.00-500.00]
NL: 1.20E6
820453237F5F4B4D9CB187BE729E
DFBD#1082-1091 RT: 14.08-14.16
AV: 10 SB: 91 5.29-5.79 , 19.42-19.66
T: {0,0} + c EI det=350.00 Full ms
[20.00-500.00]
NL: 1.67E6
820453237F5F4B4D9CB187BE729E
DFBD#1198-1215 RT: 15.05-15.19
AV: 18 SB: 91 5.29-5.79 , 19.42-19.66
T: {0,0} + c EI det=350.00 Full ms
[20.00-500.00]
26
Appendix V: Acrylamide + -SH GCMS
RT: 0.00 - 20.00
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19
Time (min)
0
5
10
15
20
25
30
35
40
45
50
55
60
65
70
75
80
85
90
95
100
Re
lative
Ab
un
da
nce
RT: 12.26
MA: 27636604
RT: 10.02
MA: 25042058
RT: 10.60
MA: 17294764
RT: 17.72
MA: 16308458
RT: 14.35
MA: 3870847
10.67
9.94
NL:
1.48E7
TIC MS
8A6BC78A
A2834923
B1166626
1A504581
RT: 8.94 - 18.74
9.0 9.5 10.0 10.5 11.0 11.5 12.0 12.5 13.0 13.5 14.0 14.5 15.0 15.5 16.0 16.5 17.0 17.5 18.0 18.5
Time (min)
0
5
10
15
20
25
30
35
40
45
50
55
60
65
70
75
80
85
90
95
100
Re
lative
Ab
un
da
nce
RT: 12.26
MA: 27636604
RT: 10.02
MA: 25042058
RT: 10.60
MA: 17294764
RT: 17.72
MA: 16308458
RT: 14.35
MA: 3870847
RT: 9.94
MA: 2381502
10.67
NL:
1.48E7
TIC MS
8A6BC78A
A2834923
B1166626
1A504581
27
20 30 40 50 60 70 80 90 100 110 120 130 140 150 160 170
m/z
0
20
40
60
80
100
0
20
40
60
80
100
0
20
40
60
80
100
Re
lative
Ab
un
da
nce
0
20
40
60
80
10077.0
106.0
51.1
50.1 78.152.1 107.174.039.138.127.1 63.049.0 79.264.1 112.1 161.6 177.4120.0 171.4133.5 145.984.0
121.1
77.1
91.175.1 122.3105.1
51.1 78.1 152.159.147.1 89.139.1 65.1 92.229.1 74.0 106.2 124.127.1 119.1103.1 135.0 149.1 154.2 176.3168.2
91.0
124.0
65.092.139.1 77.045.0 63.051.1 89.0 125.1121.0105.078.061.038.1 66.1 136.027.1 97.0 108.0 150.4142.3 164.5 168.6159.9 176.2
91.0
124.0
65.092.139.1 63.045.0 77.051.1 89.0 125.1121.078.161.038.1 66.127.1 97.0 108.0 130.1 166.6 178.5142.3 160.3146.2
NL: 2.13E5
8A6BC78AA2834923B11666261A504
581#576-580 RT: 9.92-9.95 AV: 5
SB: 139 7.96-8.56 , 18.85-19.41 T:
{0,0} + c EI det=350.00 Full ms
[20.00-500.00]
NL: 3.53E6
8A6BC78AA2834923B11666261A504
581#586-590 RT: 10.00-10.04 AV: 5
SB: 139 7.96-8.56 , 18.85-19.41 T:
{0,0} + c EI det=350.00 Full ms
[20.00-500.00]
NL: 1.70E6
8A6BC78AA2834923B11666261A504
581#652-659 RT: 10.56-10.62 AV: 8
SB: 139 7.96-8.56 , 18.85-19.41 T:
{0,0} + c EI det=350.00 Full ms
[20.00-500.00]
NL: 1.21E6
8A6BC78AA2834923B11666261A504
581#664-669 RT: 10.67-10.71 AV: 6
SB: 139 7.96-8.56 , 18.85-19.41 T:
{0,0} + c EI det=350.00 Full ms
[20.00-500.00]
20 40 60 80 100 120 140 160 180 200 220 240
m/z
0
10
20
30
40
50
60
70
80
90
100
0
10
20
30
40
50
60
70
80
90
100
Re
lative
Ab
un
da
nce
0
10
20
30
40
50
60
70
80
90
10071.0
44.127.1 55.1
43.1
28.1
72.153.0 69.956.142.1 91.0 124.077.0 92.1 108.0 157.3 192.3147.5 170.2131.8 176.0 227.7201.3 217.1 247.9238.4
91.0
45.0
168.0
65.0
92.1 200.077.039.1 121.063.051.029.1 89.0 169.0105.0 135.066.1 93.1 152.9 203.1 249.3220.2191.0164.1 232.3
121.0
91.077.0122.1
45.0 105.065.0 78.051.0 92.139.1 123.166.0 110.029.1 133.0 213.0 244.1153.0 178.1165.1 197.2191.1 231.4
NL: 2.12E6
8A6BC78AA2834923B11666261A504
581#850-855 RT: 12.24-12.28 AV: 6
SB: 139 7.96-8.56 , 18.85-19.41 T:
{0,0} + c EI det=350.00 Full ms
[20.00-500.00]
NL: 4.60E5
8A6BC78AA2834923B11666261A504
581#1099-1104 RT: 14.34-14.38 AV:
6 SB: 139 7.96-8.56 , 18.85-19.41 T:
{0,0} + c EI det=350.00 Full ms
[20.00-500.00]
NL: 1.97E6
8A6BC78AA2834923B11666261A504
581#1501-1508 RT: 17.70-17.76 AV:
8 SB: 139 7.96-8.56 , 18.85-19.41 T:
{0,0} + c EI det=350.00 Full ms
[20.00-500.00]
28
Appendix VI: Acryloyl Chloride + -SH GCMS
RT: 5.01 - 19.98
6 7 8 9 10 11 12 13 14 15 16 17 18 19
Time (min)
0
5
10
15
20
25
30
35
40
45
50
55
60
65
70
75
80
85
90
95
100
Re
lative
Ab
un
da
nce
RT: 10.60
MA: 76797384
RT: 12.81
MA: 40695426
NL:
3.36E7
TIC MS
5610E6D0
5419440F8
FCB0F642
D1911F9
20 40 60 80 100 120 140 160 180 200 220 240 260 280 300
m/z
0
10
20
30
40
50
60
70
80
90
100
0
10
20
30
40
50
60
70
80
90
100
Re
lative
Ab
un
da
nce
91.0
124.0
65.1
92.145.0
39.1
63.051.0 89.077.0125.162.0
121.078.138.1 61.0 66.1 93.2 107.9 127.2 139.3 151.6 165.2 180.8 214.1 226.4189.1 249.1 271.8 278.2238.0 298.8265.9
91.1
65.092.2 181.1 246.0
45.077.039.1 63.0 121.0 247.1182.2124.1 152.997.0 165.027.1 108.0 214.0193.1 232.0 294.0263.0 269.7
NL: 2.10E6
5610E6D05419440F8FCB0F642D19
11F9#657-672 RT: 10.57-10.70 AV:
16 SB: 139 9.11-9.80 , 17.45-17.92
T: {0,0} + c EI det=350.00 Full ms
[20.00-500.00]
NL: 2.11E6
5610E6D05419440F8FCB0F642D19
11F9#917-935 RT: 12.76-12.91 AV:
19 SB: 139 9.11-9.80 , 17.45-17.92
T: {0,0} + c EI det=350.00 Full ms
[20.00-500.00]
29
Appendix VII: Butenone + Grignard GCMS
RT: 4.97 - 20.00
5 6 7 8 9 10 11 12 13 14 15 16 17 18 19
Time (min)
0
5
10
15
20
25
30
35
40
45
50
55
60
65
70
75
80
85
90
95
100
Re
lative
Ab
un
da
nce
RT: 7.46
MA: 34702254
5.10
5.31
NL:
3.86E7
TIC MS
4019343F2
DF441938
2EBF016A
6AE8F62
4019343F2DF4419382EBF016A6AE8F62 #287-297 RT: 7.42-7.51 AV: 11 SB: 30 17.77-18.00 , 6.04 NL: 1.31E6
T: {0,0} + c EI det=350.00 Full ms [20.00-500.00]
50 100 150 200 250 300 350 400 450 500
m/z
0
5
10
15
20
25
30
35
40
45
50
55
60
65
70
75
80
85
90
95
100
Re
lative
Ab
un
da
nce
43.1
45.1
87.1
71.1
55.175.129.1
102.1
59.1
88.1103.1 122.0 174.5136.5 241.7213.3 323.4183.7 474.2341.7 390.9 492.4447.9266.6 309.6276.1 429.5380.2361.8 403.3166.1
30
Appendix VIII: Predicted NMR for Butenone + thiol Reaction
31
32
Appendix IX: Actual NMR for Butenone + thiol Reaction
33
34
Bibliography
Fleming: Molecular Orbitals and Organic Chemical Reactions, Student Edition, Wiley, 2009
Vollhardt, Shore: Organic Chemistry, Structures and Functions, Freeman
Clayden, Greeves, Wareen, Wothers: Organic Chemistry, Oxford, 2001
Solomons, T.W.Graham: Organic Chemistry, 7th
Edition, Wiley, 2000
McMurry: Organic Chemistry, 5th
Edition, Brooks/Cole, 2000
Jones Jr.: Organic Chemistry, 3rd
Edition, Norton, 1997
Mather, Viswanathan, Miller, Long: Michael Addition reaction in macromolecular design for
emerging technologies, 2006
http://en.wikipedia.org/wiki/HSAB_theory
http://en.wikipedia.org/wiki/Michael_reaction
www2.trincoll.edu/~tmitzel/chem211fold/classnotes/1126_mon/1126_mon.htm
http://www.mhhe.com/physsci/chemistry/carey/student/olc/graphics/carey04oc/ref/ch18reactionconjugated.html
http://cnx.org/context/m15243/latest
Figure 3,5 taken from
http://www.mhhe.com/physsci/chemistry/carey/student/olc/graphics/carey04oc/ref/ch18reactionconjugated.html
Other figures drawn by ChemDraw.