Nucleophilic Addition on ,-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

Contents Abstract Introduction P.3 P.3-7

1. Lewis Acid and Base, HSAB : Nucleophiles Thiols and Grignard Reagents 2. ,-unsaturated carbonyl compounds and nucleophile addition with these compounds 3. Conjugation Addition and Michael Addition

Experimental Part Results Discussion Conclusion Appendix

I. II. III. IV. V. VI. VII. VIII. IX.

P.8-10 P.10-11 P.12-17 P.17-18 P.19-33

Butenone + Thiol Reaction GCMS Phenyl Butenone + Thiol Reaction GCMS Pentenone + Thiol Reaction GCMS Methyl Hexenone + thiol reaction GCMS Acrylamide + Thiol Reaction GCMS Acryloyl Chloride + Thiol Reaction GCMS Butenone + Grignard Reaction GCMS Predicted NMR for Butenone + Thiol Reaction Actual NMR for Butenone + Thiol Reaction

Bibliography

P.34

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 ,-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 ,-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 Brnsted and Thomas Martin Lowry in 1923, Brnsted Lowry acidbase 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-likessoft. 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

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
1

4 www2.trincoll.edu/~tmitzel/chem211fold/classnotes/1126_mon/1126_mon.htm, accessed 24th July

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 8 of 8.1eV, which is comparatively very soft comparing to hydroxide ion that has of 12eV. 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

The C-Mg bond is polarized as the Magnesium is less electronegative than Carbon. The CMg bond is hence polarized towards the carbon, and the carbon would then attack electrophile as it is partially positive. 2) ,-unsaturated carbonyl compounds and nucleophile addition with

these compounds
,-unsaturated carbonyl compounds are ketones or aldehydes that have a double bond conjugated with a carbonyl group. The carbon refers to the carbon atom next to the carbonyl, and the next carbon is the 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 carbon, making the carbon more electron-deficient and electrophilic than a normal alkene. The C=C double bond is therefore relatively electron poor.

Figure 1

Figure 2

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. ,-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

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

Figure 3

Figure 4

Figure 3 and 4 show the resonance structure of ,-unsaturated carbonyl compounds. Due to the resonance, the carbon and the carbonyl carbon both carry a partially positive charge, making a nucleophilic attack possible at these two sites.

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 carries some positive charge, the 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 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 5 (a) and (b)

Figure 5(a) and (b) shows how the nucleophilc would attack the carbon in 1,2 and 1,4direction respectively.

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 carbon of a ,-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 1,4conjugate 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 ,-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 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

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 )

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.

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 4-Phenyl-3-buten2-one 3-penten-2-one 5-methyl-3-hexen2-one Acrylamide Acryloyl Chloride

H C6H5 CH3 C3H7 H H

CH3 CH3 CH3 CH3 NH2 Cl

(82%)

NA NA NA NA NA

(44%) ( 40%)

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1). Butenone + thiol Reaction A). NMR

Desired Conjugate addition Product for Benzyl Mercaptan + Butenone Reaction Protons A B C D E Carbons A B C D E F

2.06 2.59 2.59 3.68 7.17-7.27

Table 1, 1H NMR chemical shift for Benzyl Mercptan + butenone Reaction

29.9 206.7 43.3 25.2 36.7 127.0-138.2

Table 2, 13C NMR Chemical Shift for Benzyl Mercaptann + Butenone Reaction

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 [ 87[H2CCH3CH2COCH3].

], 29 [H2CCH3], 43[H2CCH3CH2], 55[H2CCH3CH2C],

11

Discussions 1). Thiol Reaction:

All Michael Acceptors used in this experiment are ,-unsaturated carbonyl compounds that have a double bond conjugated with a carbonyl group. The electronegative oxygen would withdraw electron density from the 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 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:

Reaction between thiol and butanone.

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 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

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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

delocalized charges throughout the whole compound

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 electrondeficient 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-2one 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 carbon also hinders attack from nucleophiles.

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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.

Conjugation of 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 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

14

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 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

15

1,4-addition between Grignard and Butenone

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 1,2addition 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

16

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

17

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.

18

Appendix
Appendix I : Butenone + -SH GCMS
RT: 4.97 - 19.99 100 95 90 85 80 75 70 65 60 RT: 15.34 MA: 420850264 NL: 6.35E7 TIC MS 9E690E8E 3A0343648 A860B646 1761252

Relative Abundance

RT: 11.01 MA: 175634804

55 50 45 40 35 30 25 20 15 10 5 0 5 6 7 8 9 10 11 12 13 Time (min) 14 15 16 17 18 19

100 90 80 70

103.1

131.1 145.1 146.1

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]

77.1

Relative Abundance

60 50 40 30 20 50.0 10 27.2 0 100 90 80 70 194.1 60 50 40 30 20 10 0 20 40 60 80 100 120 140 m/z 160 39.1 51.1 27.2 28.2 55.0 63.0 71.0 79.1 93.3 104.1 77.0 89.0 102.0 136.0 121.0 125.1 137.1 151.0 161.1 175.9 181.0 180 160.1 195.1 196.1 212.7 219.0 200 220 234.3 243.4 240 45.0 92.1 124.1 122.0 65.0 39.1 63.1 57.7 76.0 73.0 78.1 102.0 43.0 51.1

104.3 110.4 115.0

132.1 138.4

84.6

147.2 153.4 154.4 164.9 182.3 197.1 203.7 214.4 226.3 236.1 248.8 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]

98.1

127.1

91.0

43.0 123.0

19

Appendix II: Phenyl Butenone + -SH GCMS

RT: 5.08 - 19.99 100 95 90 85 80 75 70 65 60
Relative Abundance

RT: 13.32 MA: 62554118

NL: 3.37E7 TIC MS 144724790 6D541578 080825E9 C215351

55 50 45 40 35 30 25 20

RT: 10.59 MA: 45253482

RT: 10.01 MA: 15361530 RT: 17.70 MA: 22127953 RT: 12.85 MA: 43230316

15 10 5 0 6 7 8 9 10 11 12 13 Time (min) 14 15 16 17 18 19

100 90 80 70 60 50 40 30 20 10 29.1 0 100 90 80

Relative Abundance

121.1

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]

77.0 91.0 75.0 47.1 51.1 59.0 78.1 92.1 91.0 105.0 106.1 122.1 123.4 135.4 152.1 170.3 179.6 194.2 214.5 234.2 241.4 258.3 272.6 279.5 296.4 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] 124.0

70 60 50 40 30 20 39.1 45.0 10 0 100 90 80 70 60 50 40 30 20 65.0 10 0 20 27.1 39.1 45.0 40 63.0 60 77.0 80 92.2 97.0 105.0 100 121.0 125.1 120 140 152.9 165.0 160 m/z 181.0 183.3 180 246.0 248.1 259.7 207.5 214.0 219.6 236.2 200 220 240 260 27.1 38.1 63.0 77.0 61.0 66.1 65.1 92.2 97.0 91.0 121.0 125.1 136.2 153.2 166.4 180.6 189.9 205.6 215.2 227.9 242.5 259.0 267.2 292.2

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]

283.2 289.7 280

20

100 90 80 70
Relative Abundance

103.0

131.0

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]

145.1 146.1

77.0 60 50 40 43.0 30 20 10 27.1 0 100 90 80 70 60 50 40 30 20 77.0 10 0 26.1 29.1 20 30 39.1 40 45.0 51.1 50 63.0 60 65.0 66.1 70 78.1 80 89.0 92.1 90 100 105.0 110.0 110 m/z 120 91.0 122.1 123.1 133.1 130 140 145.0 153.0 150 160 165.1 170 178.1 180 192.4 197.1 190 50.0 52.0 44.1 63.0 76.0 73.0 101.9 104.2 39.1 38.1 78.1 89.0 91.0 100.9 105.2 121.0 115.0 117.1 132.1 147.2 148.6 155.6 163.7 170.3 181.2 191.9 197.1 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] 51.1

133.4

21

Appendix III: Pentenone + -SH GCMS

RT: 5.00 - 19.95 100 95 90 85 80 75 70 65 60 RT: 14.81 MA: 89589067 NL: 3.62E7 TIC MS 5E12C93837 784322AB03 0E52B85279 CB_0720201 1115136

Relative Abundance

55 50 45 40 35 30 25 20 15 10 5 0 6 7 8 9 10 11 12 13 Time (min) 14 15 16 17 18 19 RT: 6.53 MA: 26594171 RT: 10.01 MA: 6880822 RT: 13.93 MA: 7132757 RT: 10.59 MA: 14154368 RT: 15.14 MA: 11389524 RT: 7.45 MA: 47406516

14.69

100 55.1 80 60 40 29.1 20 0 100 27.1 26.1 38.1 51.1 43.1 59.1 43.1 39.1 69.0 53.1

83.0

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] 98.1

84.1 56.1 67.0 70.1 79.1 89.1 99.1 106.0 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] 101.1

Relative Abundance

80 60 40 20 0 100 80 60 40 31.1 42.1 39.1 27.1 44.1

58.0

60.1

69.0 75.0

84.0 86.1 83.0

98.1

102.1

115.1 121.0 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]

77.0 20 0 100 80 60 40 20 0 20 27.1 38.1 30 39.1 45.0 51.1 40 50 65.0 63.0 60 69.0 70 77.0 80 89.0 90 92.1 97.0 105.0 100 110 m/z 121.0 120 125.1 130 136.0 140 150 160 170 180 190 200 124.0 27.1 29.1 39.1 47.1 51.0 59.0 65.0 75.0 78.1 74.0 91.0 89.0 105.0 92.1 119.0 122.2 123.1 152.0 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]

91.0

22

100 90 80 70 60 50 40 30 20 10 0 100 90 80 43.0 47.1 65.0 59.0 31.1 45.0

75.0

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]

91.0

76.1

92.1 99.0 117.0 124.0 129.0 91.0

163.0

194.1 196.1

226.1 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]

Relative Abundance

70 60 50 40 30 20 10 27.1 0 100 43.0 90 80 70 60 50 40 30 20 10 0 20 40 60 80 29.1 39.1 45.0 57.1 65.0 77.0 85.1 99.1 39.1 51.0 59.0 77.0 89.0 100.9 91.0 45.0 65.0 92.2

123.0 117.1

208.1 124.1 135.0 150.0 165.0 174.1 181.1 190.0 209.2 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]

122.0 123.0

124.0 125.1 140 m/z 149.0 164.0 166.1 179.1 160 180 200 222.1 220 240 260

100.1 120.9 100 120

23

Appendix IV: Methyl Hexenone + -SH GCMS

RT: 5.00 - 19.95 100 95 90 85 80 75 70 65 60 RT: 15.12 MA: 85037762 NL: 3.19E7 TIC MS 820453237 F5F4B4D9 CB187BE7 29EDFBD

Relative Abundance

55 50 45 40 35 30 25 20 15 10 5 0 5 6 7 8 9 10 11 12 13 Time (min) 14 15 16 17 18 19 RT: 12.83 MA: 33642304 RT: 7.73 MA: 31024453 RT: 8.48 MA: 37888556

RT: 10.23 MA: 15163067 10.02 RT: 14.11 MA: 11624928

100 80 60 40 20 0 100 80 60 40 20 0 100 80 60 40 26.1 29.1 27.1 26.1 29.1

43.1 41.1

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] 112.1

97.1 69.1

39.1 53.1 50.1 43.1

55.1 58.1 67.1

70.1 79.0

81.0

95.1

98.1

102.1

113.2

127.1

138.4 143.1

153.3 159.1

172.4

182.3 192.6 197.6 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]

Relative Abundance

101.0

55.1 41.1 45.1

59.1 69.1 71.0 83.0 87.1 86.1 88.1 97.1 112.1 114.1 121.1 129.1 131.1 144.1 150.3 159.6 170.1 175.9 182.2 192.2 200.1 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]

77.0 20 0 100 80 60 40 20 27.1 29.1 0 20 30 40 50 60 70 80 41.1 44.1 55.1 73.1 69.1 75.1 88.1 97.1 98.1 90 100 112.0 115.1 110 m/z 120 129.1 130 141.1 146.1 140 150 158.3 160 168.6 176.3 183.2 191.5 198.3 170 180 190 200 26.1 29.1 51.1 39.1 47.1 43.1 75.0 78.1 59.0 65.0 74.0 91.0 89.0 105.0 95.1 97.1 122.1 127.1 135.0 143.1

117.0

152.1 155.1 167.1

180.1 187.2

199.2 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]

87.1

58.1 59.1

24

100 90 80 70 60 50 40 30 20 65.0 10 0 100 90 80

Relative Abundance

91.1

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]

39.1 45.0

63.0

75.0 77.0 75.0

92.1 97.0 112.1 121.0 125.0 153.0 165.0

181.1 182.9 194.1

213.0 225.1 235.5

246.1 249.1 266.4

286.8 297.5 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]

70 60 50 40 30 20 10 0 100 90 80 70 60 50 40 30 20 10 0 40 60 80 100 120 140 41.1 27.1 45.0 55.1 65.0 69.1 87.0 95.1 111.1 92.1 124.1 146.1 173.3 178.0 160 m/z 180 193.1 202.1 200 231.3 220 236.1 237.2 246.4 240 269.1 279.1 280 295.7 300 123.0 144.0 145.1 43.1 31.1 45.1 47.1 65.0 76.1 91.0 99.1 111.0 124.0 137.0 145.1 222.1 91.0

165.1

179.1 191.1

207.1

225.2

254.1

269.2 280.7

293.6 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]

260

25

Appendix V: Acrylamide + -SH GCMS

RT: 0.00 - 20.00 100 95 90 85 80 75 70 65 60 RT: 10.60 MA: 17294764 RT: 10.02 MA: 25042058 RT: 12.26 MA: 27636604 NL: 1.48E7 TIC MS 8A6BC78A A2834923 B1166626 1A504581

Relative Abundance

55 50 45 40 35 30 25 10.67 20 15 10 5 0 0 1 2 3 4 5 6 7 8 9 10 Time (min) 11 12 13 14 15 16 17 18 19 9.94 RT: 14.35 MA: 3870847

RT: 17.72 MA: 16308458

RT: 8.94 - 18.74 100 95 90 85 80 75 70 65 60 RT: 10.60 MA: 17294764 RT: 10.02 MA: 25042058 RT: 12.26 MA: 27636604 NL: 1.48E7 TIC MS 8A6BC78A A2834923 B1166626 1A504581

Relative Abundance

55 50 45 40 35 30 25 10.67 20 15 10 5 0 9.0 9.5 10.0 10.5 11.0 11.5 12.0 12.5 13.0 13.5 14.0 Time (min) 14.5 15.0 15.5 16.0 16.5 17.0 17.5 18.0 18.5 RT: 9.94 MA: 2381502 RT: 14.35 MA: 3870847

RT: 17.72 MA: 16308458

26

100 80 60 40 20 27.1 0 100 38.1 39.1 51.1 50.1 52.1 49.0 63.0 64.1

77.0

106.0

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]

78.1 74.0 107.1 79.2 84.0 112.1 120.0 121.1 133.5 145.9 161.6 171.4 177.4 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] 77.1 91.1 75.1

Relative Abundance

80 60 40 20 0 100 80 60 40 20 0 100 80 60 40 20 0 20 27.1 30 38.1 39.1 45.0 40 65.0 51.1 61.0 63.0 50 60 66.1 70 77.0 78.1 89.0 80 90 92.1 97.0 100 m/z 108.0 110 121.0 125.1 130.1 120 130 142.3 146.2 140 150 160.3 166.6 160 170 178.5 124.0 27.1 38.1 39.1 45.0 65.0 51.1 61.0 63.0 66.1 77.0 78.0 89.0 92.1 97.0 105.0 108.0 121.0 125.1 136.0 142.3 150.4 159.9 164.5 168.6 176.2 124.0 27.1 29.1 39.1 47.1 51.1 59.1 65.1

105.1 78.1 89.1 92.2 91.0 103.1 106.2 119.1

122.3 124.1 135.0 149.1 152.1 154.2 168.2 176.3 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]

74.0

91.0

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]

100 90 80 70 60 50 40 30 20 10 0 100 90 80 45.0 28.1 42.1 43.1 27.1 44.1

71.0

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]

55.1

53.0 56.1 69.9 72.1 77.0 91.0 92.1 108.0 91.0

124.0 131.8

147.5 157.3

170.2 176.0

192.3 201.3

217.1

227.7

238.4 247.9 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]

Relative Abundance

70 60 50 40 30 20 10 0 100 90 80 70 60 50 40 30 20 10 0 20 45.0 51.0 29.1 39.1 40 60 65.0 77.0 66.0 78.0 80 91.0 122.1 92.1 105.0 110.0 120 m/z 123.1 133.0 140 153.0 165.1 160 178.1 191.1 197.2 180 200 213.0 220 231.4 244.1 240 29.1 39.1 51.0 65.0 63.0 66.1 77.0 92.1 89.0 93.1 105.0 121.0 121.0 135.0 152.9 164.1 169.0 200.0 191.0 203.1 220.2 232.3 249.3 168.0

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]

100

27

Appendix VI: Acryloyl Chloride + -SH GCMS

RT: 5.01 - 19.98 100 95 90 85 80 75 70 65 60 RT: 10.60 MA: 76797384 NL: 3.36E7 TIC MS 5610E6D0 5419440F8 FCB0F642 D1911F9

Relative Abundance

55 50 45 40 35 30 25 20 15 10 5 0 6 7 8 9 10 11 12 Time (min) 13 14 15 16 17 18 19

RT: 12.81 MA: 40695426

100 90 80 70

91.0

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] 124.0

Relative Abundance

60 50 40 30 20 10 38.1 0 100 90 80 70 60 50 40 30 20 65.0 10 0 20 27.1 39.1 45.0 63.0 60 77.0 80 92.2 97.0 108.0 100 121.0 124.1 120 140 152.9 165.0 160 m/z 181.1 182.2 193.1 180 200 214.0 220 232.0 240 246.0 247.1 263.0 269.7 260 280 294.0 300 39.1 45.0 51.0 63.0 62.0 61.0 77.0 89.0 66.1 78.1 121.0 93.2 107.9 91.1 125.1 127.2 139.3 151.6 165.2 180.8 189.1 214.1 226.4 238.0 249.1 265.9 271.8 278.2 298.8 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] 92.1 65.1

40

28

Appendix VII: Butenone + Grignard GCMS

RT: 4.97 - 20.00 100 95 90 85 80 75 70 65 60 5.10 NL: 3.86E7 TIC MS 4019343F2 DF441938 2EBF016A 6AE8F62

Relative Abundance

55 50 45 40 35 30 25 20 5.31 15 10 5 0 5 6 7 8 9 10 11 12 13 Time (min) 14 15 16 17 18 19 RT: 7.46 MA: 34702254

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] 43.1 100 95 90 85 80 75 70 65 60 45.1

Relative Abundance

55 50 45 40 35 30 25 20 15 10 5 0 50 100 59.1 88.1 103.1 122.0 136.5 166.1 174.5 183.7 150 200 213.3 241.7 250 m/z 266.6 276.1 309.6 323.4 300 341.7 361.8 380.2 390.9 403.3 350 400 429.5 447.9 450 474.2 492.4 500 29.1 55.1

87.1

71.1 75.1 102.1

29

Appendix VIII: Predicted NMR for Butenone + thiol Reaction

30

31

Appendix IX: Actual NMR for Butenone + thiol Reaction

32

33

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/ch18r eactionconjugated.html http://cnx.org/context/m15243/latest
Figure 3,5 taken from

http://www.mhhe.com/physsci/chemistry/carey/student/olc/graphics/carey04oc/ref/ch18r eactionconjugated.html Other figures drawn by ChemDraw.

34