1

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

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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

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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.

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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.

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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

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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.

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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

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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.