Experiment 1 : The Wittig and Suzuki reaction - h. W · Experiment 1 : The Wittig and Suzuki reaction ... alkyl halide to give an ... In this lab you will prepare either a stabilised

7

Experiment 1 : The Wittig and Suzuki reaction

Introduction

The Wittig reaction is named after its discoverer, Georg Wittig, winner of the 1979 Nobel Prize

for Chemistry. It is an effective way of making an alkene carbon–carbon double bond from an

aldehyde or ketone with the help of an organophosphorus intermediate. The Wittig reaction (see also

Clayden, Organic Chemistry, pp. 689 – 693) will be discussed in more detail in Organic Reactions I.

Triphenylphosphine (PPh3) is a good nucleophile and can easily undergo an SN2 reaction with a

primary (or secondary) alkyl halide to give an alkyltriphenylphosphonium salt (1) in high yield.

Deprotonation of the phosphonium salt 1 with a suitable base results in the reactive intermediate 2,

also called an ylide or a phosphorane. You can regard a phosphorane as an organophosphorus

compound with a formal double bond between phosphorus and carbon (2A); its reactivity is best

described by the alternative resonance structure of ylide 2B with a negative charge on carbon which

is stabilised by electron-donation into the d-orbitals of the phosphorus.

2A

PPh3 XR1

R2

X = Cl, Br, I

Ph3PR1

R2

X

HH Ph3PR1

R2

basePh3P

R1

R2

12B

The Wittig reagent 2 reacts with an aldehyde or a ketone to give an alkene. The alkene C=C bond

will always end up exactly where the C=O group was before, and the oxygen atom of the carbonyl

compound is formally replaced by the =CR1R2 part of the phosphorane.

R'R

O

3

Ph3PR1

R2

R = alkyl, aryl or H

OPh3P

R1

R2 RR'

Ph3P O

R1

R2 RR'

4oxaphosphetane

R'

R

R1

R2Ph3P O

The Wittig reaction is very versatile and suitable for making mono-, di- and trisubstituted alkenes.

Tetrasubstituted alkenes cannot be obtained due to steric hindrance. The reaction proceeds via a 4-

membered cyclic intermediate called an oxaphosphetane (4) which is formed by a [2 + 2]

cycloaddition but may occasionally proceed via a betaine-type transition state 3. The other product

of the reaction is triphenylphosphine oxide. The high strength of the P=O double bond is the

thermodynamic driving force behind the Wittig reaction.

In this lab you will prepare either a stabilised or a non-stabilised ylide and investigate whether

Experiment

1

8

there is a preference for forming an E or a Z (trans or cis) alkene or a mixture of the two isomers. A

stabilised ylide results when one of the substituents next to the negatively charged ylide carbon is an

electron-withdrawing group. The fact that you can isolate such an ylide and run an NMR spectrum

already tells you why it is called a “stabilised ylide”.

Unstabilised ylides (where R1 and R2 are alkyl groups or H) normally require strong bases such as

BuLi or PhLi which are not only expensive but also demand special care and attention when working

with them. In Experiment 1C, you will make use of phase transfer catalysis where the phosphonium

salt (itself slightly soluble in organic solvents) helps to drag hydroxide ions (normally not soluble in

nonpolar organic solvents) into the organic phase. There, hydroxide is sufficiently strong to

deprotonate the benzyltriphenylphosphonium salt and generate the ylide.

The Suzuki coupling, also often called the Suzuki-Miyauri cross-coupling, is an example of a Pd-

catalysed coupling reaction (see also Clayden, Organic Chemistry, pp. 1082 – 1087). The 2010 Nobel

Prize in Chemistry was awarded to Richard Heck, Ei-ichi Negishi, and Akira Suzuki, who won it

jointly for their work on palladium-catalyzed cross couplings in organic synthesis.

The Suzuki coupling is a very useful and mild method for making carbon–carbon sigma bonds. In

a Suzuki reaction, an aryl (or vinyl) halide is coupled with a boronic acid Ar-B(OH)2 (or a boronic

ester) in the presence of catalytic amounts of a palladium(0) catalyst which is often generated in situ

from PdCl2 or Pd(OAc)2 and a phosphine (e.g. PPh3). The mechanism involves the oxidative addition

of the aryl halide onto the Pd(0) catalyst, a transmetallation step where the intermediate Pd(II)

complex replaces the boronic acid group of the aryl boronic acid component, and finally a reductive

elimination leading to the product and the regeneration of the Pd(0) catalyst. A simplified mechanism

is shown below. The Suzuki coupling requires a base (e.g. sodium hydroxide, triethylamine, sodium

carbonate, potassium acetate) which is thought to activate the boronic acid to a negatively charged

boronate to aid transmetallation.1

1 This view has been questioned recently and several groups have suggested that the reaction involves a palladium hydroxo complex: B. P. Carrow and J. F. Hartwig, J. Am. Chem. Soc., 2011, 133, 2116.

9

Unlike other organometallic reactions such as the Grignard reaction, the Suzuki coupling does not

require anhydrous conditions and a little water actually helps with the solubilisation of all reactants.

Suzuki reactions also tolerate a wide range of functionality (e.g. carbonyl groups) that would be

incompatible with a Grignard reagent.

Aryl iodides as coupling components are more reactive than aryl bromides, but are also more

expensive. Aryl chlorides have a very low reactivity and need a highly active (and also more difficult

to make) Pd(0) catalyst. Aryl triflates Ar-OSO2CF3 — made from phenols (Ar-OH) and triflic

anhydride = trifluoromethanesulfonic acid anhydride (CF3SO2)2O — are equally suitable coupling

components, especially if the phenol is more readily available than the aryl bromide. The order of

reactivity is: I > OTf > Br >> Cl.

The Suzuki coupling is a very powerful synthetic method for making substituted biphenyls and

other biaryls. This has found a practical application in natural product synthesis and, more recently,

in making a new generation of pharmaceutical drugs containing unsymmetrical biphenyl units and

even light-emitting polymer semiconductors for organic light-emitting diodes (OLEDs). Examples

of pharmaceutical drugs made by the Suzuki reaction are angiotensin II receptor antagonists losartan

and valsartan (for the treatment of high blood pressure). The fungicide boscalid is used for protecting

specialty crops such as apples, cucumbers, roses against fungal diseases. Although the catalyst

appears to be comparatively expensive at a first glance, in an industrial process the Pd is always

recovered and converted back into Pd(OAc)2 or PdCl2.

Boscalid (fungicide)BASF

1000 tonnes/year

Polyfluorene (blue OLED)Dow Chemical &

Cambridge Display Technology Ltd.

NNN N

NH

Valsartan (hypertension treatment)Novartis

4.09 Mrd $ in annual sales

O

CO2H

ClHN O

C8H17 C8H17n

Suzuki couplingSuzuki coupling

Cl

Suzuki coupling

PRE-LAB EXERCISES

a. Watch the following video in preparation of your experiment: Chromatography: Thin-

layer chromatography. Read through Appendix 5 on “Ultraviolet-visible spectroscopy”.

b. Do the pre-lab webtest for Experiment 1 on VISION.

c. Prepare a table of reagents in your lab book.

10 1A Wittig reaction with a stabilised ylide

Safety Notes

(Carbethoxymethyl)triphenylphosphonium chloride, (ethoxycarbonylmethylene)triphenylphosphorane:

Causes skin and serious eye irritation; may cause respiratory irritation; toxic if swallowed.

Sodium hydroxide: Very corrosive: causes severe burns; in case of contact with eyes, rinse immediately with

plenty of water and seek medical advice.

Anthracene-9-carbaldehyde: Not yet tested, treat as harmful.

Methanol: Toxic by inhalation, in contact with skin and if swallowed can cause irreversible

damage to the eyes; highly flammable liquid and vapour.

Petroleum ether: Highly flammable liquid and vapour — make sure there are no naked flames

nearby; vapours may cause drowsiness and dizziness; suspected of damaging fertility or the unborn child; harmful: may

cause lung damage if swallowed; toxic to aquatic organisms.

Ethyl acetate: Highly flammable liquid and vapour; causes serious eye irritation; vapours may cause

drowsiness and dizziness.

Ph3PCH2CO2Et

Cl

NaOHX

OH

1A

Anthracene-9-carbaldehydeC22H22ClO2P

(384.84)C15H10O(206.24)

C22H22BrO2P(429.29)

Bror

To carry out the Wittig reaction

In a conical flask, dissolve 5 mmol of the crude phosphonium salt in ice-cold water (50 mL),

add a drop of phenolphthalein solution, then “titrate” to pH 9 by dispensing 2 M NaOH

solution from a disposable plastic pipette. Collect the precipitate2 by suction filtration, wash

with water and a small (!) amount of methanol, and dry thoroughly for at least 2 days. Record

the yield of X and its melting point.

Suspend anthracene-9-carbaldehyde (0.577 g, 2.8 mmol) in dry methanol (20 mL) in a clean

and dry round-bottom flask. Add 1.0 g of X and continue stirring at room temperature for 30

minutes when you should have obtained a clear solution. Concentrate the solution on a rotary

evaporator. Subsequently, triturate the residue with petroleum ether (20 mL) and stir gently.

2 You may need to scratch the glass to cause crystallisation of the product.

11

Filter the suspension using a Büchner funnel. Rinse the reaction flask with petroleum ether

and filter again (What is the insoluble residue?). Concentrate the filtrate using a rotary

evaporator. Recrystallise the product 1A from methanol.

In addition to the standard characterisation, record a UV-vis spectrum3 (300 – 800 nm) and

check the purity of your product by TLC (petroleum ether/ethyl acetate, 5:1).4

Results & Discussion

Here is an expansion of the 1H NMR spectrum (200 MHz, CDCl3) of the recrystallised product:

(a) Analyse the complete spectroscopic data for your product. The 1H NMR spectrum is also

available online on VISION. Suggest a structure for the product of your Wittig reaction,

including its stereochemistry.

(b) While experiment 1A gives an alkene with exclusively one stereochemistry, compare this

result with the crude product obtained in experiment 1B (you will need to take a look at the 1H NMR spectra on pp. 15 – 16). What conclusions can you draw for the cis/trans selectivity

of the Wittig reaction involving stabilised/non-stabilised ylides?

3 Dissolve 1 mg of product in 20 mL of methanol. No UV-Vis spectrophotometer can measure absorbances greater than 2 accurately, and therefore, if the longest wavelength absorbance turns out too high, take 2 mL of your solution and dilute by a factor of 2, 5 or 10 so that your maximum absorbance between 300 and 400 nm is about 1 to 1.5. 4 Use a UV lamp to detect your TLC spots (it is always a good idea to check your TLC plate before running the TLC that there is enough UV-active compound on it).

6.46.46.66.66.86.87.07.07.27.27.47.47.67.67.87.88.08.08.28.28.48.48.68.612

78.5

5

1736

.88

1294

.79

1686

.22

1720

.64

4.504.50 1.501.50

882.

587

5.4

868.

2

285.

029

2.0

277.

0

889.

7

12 1B Wittig reaction with a "non-stabilised" ylide

Safety Notes

Triphenylphosphine: Harmful if swallowed; may cause an allergic skin reaction; may cause long lasting harmful

effects to aquatic life.

1,4-Bis(chloromethyl)benzene: Harmful if swallowed; causes skin irritation; causes serious eye

irritation; very toxic to aquatic life.

Dimethylformamide (DMF): Flammable liquid and vapour; harmful in contact with skin;

causes serious eye irritation; harmful if inhaled; may damage fertility or the unborn child. Avoid skin contact with

dimethylformamide.

Diethyl ether: Extremely flammable liquid and vapour — make sure there are no naked flames or hot

surfaces nearby as diethyl ether ignites readily even when getting in contact with a heated hotplate; may form explosive

peroxides; harmful if swallowed; vapours may cause drowsiness and dizziness.

p-Xylylenebis(triphenylphosphonium chloride): Irritating to eyes, respiratory system and skin.

Benzaldehyde: Harmful if swallowed.

Sodium ethoxide: Self-heating; may catch fire; causes severe skin burns and eye damage; in case of

contact with eyes, rinse immediately with plenty of water and seek medical advice.

Methylated spirits: Highly flammable liquid and vapour.

Toluene: Highly flammable liquid and vapour; suspected of damaging fertility or the unborn

child; irritating to the skin; harmful: danger of serious damage to health by prolonged exposure through inhalation;

vapours may cause drowsiness and dizziness; harmful: may cause lung damage if swallowed.

Iodine: Harmful in contact with skin and if inhaled; very toxic to aquatic life.

Petroleum ether: Highly flammable liquid and vapour — make sure there are no naked flames

nearby; vapours may cause drowsiness and dizziness; suspected of damaging fertility or the unborn child; harmful: may

cause lung damage if swallowed; toxic to aquatic organisms.



13

PPh3

2 Cl

NaOEt

OH

1B

C18H15P(262.29)

C7H6O(106.12)d 1.044

(68.05)

CH2Cl

CH2Cl

CH2-PPh3

CH2-PPh3

C44H38Cl2P2(699.63)

C8H8Cl2(175.05)

To prepare the phosphonium salt

Reflux a mixture of triphenylphosphine (2.85 g, 11.0 mmol, 2.2 equiv.), 1,4-

bis(chloromethyl)benzene (0.875 g, 5.00 mmol) and DMF (10 mL) for 3 hours using an

isomantle. A crystalline solid should separate after half an hour. Allow the mixture to cool

to room temperature, then cool with an ice–water bath. Filter the crystalline product, wash

with a small amount of DMF followed by diethyl ether, dispose of the filtrate, then apply

suction to the filtered p-xylylenebis(triphenylphosphonium chloride) until the product is dry.

Determine the yield.


Dissolve benzaldehyde (6.5 mmol, 2.6 equiv.) and p-

xylylene-bis(triphenylphosphonium chloride) (1.75 g,

2.5 mmol) in dry ethanol (15 mL). Add a solution of

sodium ethoxide (6.25 mmol, 2.5 equiv.) in dry ethanol

(30 mL) and stir at room temperature for 2 hours. Add

water (ca. 25 mL) and collect the precipitate by suction

filtration. Wash with 60% methylated spirits and air-

dry the product for at least 2 days. Recrystallise the crude product from toluene in the presence

of a trace of iodine. In addition to the standard characterisation, take also a UV-vis spectrum5

of your product (200 – 800 nm) and confirm the purity of your product by TLC (petroleum

ether/ethyl acetate, 5:1).6


Here is an expansion of the 1H NMR spectrum (400 MHz, CD2Cl2) of the recrystallised product:

5 Dissolve 1 mg of product in 20 mL of CH2Cl2. No UV-Vis spectrophotometer can measure absorbances greater than 2 accurately, and therefore, if the longest wavelength absorbance turns out too high, take 2 mL of your solution and dilute by a factor of 2, 5 or 10 so that your maximum absorbance between 300 and 400 nm is about 1 to 1.5. Store your sample out of sunlight, e.g. in the dark in your bench cupboard, since distyrylbenzenes are subject to photooxidation (bleaching) as well as photochemically induced cis/trans isomerisation. 6 Use a UV lamp to detect your TLC spots (it is always a good idea to check your TLC plate before running the TLC that there is enough UV-active compound on it).

14

(a) Analyse the spectroscopic data for your product (the 1H NMR spectra are available on

VISION).

Suggest a structure for the product of your Wittig reaction, including its stereochemistry.

Hint: Two spins coupling to each other will usually give rise to two doublets. We call them

an AX spin system when the signals are far apart, and an AB spin system when they get closer

together. You get an AB system when the chemical shift difference in Hertz ∆ν = νA – νB is

similar in size to the coupling constant JAB (∆ν ≤ 3 × JAB). Spectra of the AB type show small

outer lines (f1 and f4) and large inner lines (f2 and f3) due to a strongly pronounced roofing

effect. Note that, in this higher-order spin system, the chemical shift is no longer at the

geometric centre of the signal but at the “centre of gravity” between lines 1 and 2 for νA, and

between lines 3 and 4 for νB. You will therefore need to calculate the precise chemical shifts.

For this, use the following equations to properly analyse an AB spin system. Don’t forget to

divide the frequency ν values by the NMR frequency (400.13 MHz) to get the chemical shift

values in ppm.

JAB JAB

f1

f2 f3

f4

νZ νBνA

( )( )3241

ffff −−=∆ν

2ZAν∆νν +=

2ZBν∆νν −=

4321ffffJ

AB−=−=

∆ν

15

(b) Compare this with the 1H NMR spectrum (400 MHz, CDCl3) of the crude product:

Hint: A cis-stilbene and a trans-stilbene have not only characteristic coupling constants, but

also show a clear difference in the alkene proton chemical shift.

(c) Experiment 1A gives an alkene with exclusively one stereochemistry (just look at the 1H NMR

spectrum on p. 12). What conclusions can you draw for the cis/trans selectivity of the Wittig

reaction involving stabilised/non-stabilised ylides?

7.7 7.6 7.5 7.4 7.3 7.2 7.1 7.0 6.9 6.8 6.7

CHCl3

X

7.30 7.25 7.20 7.15 7.10 7.05 7.00 6.95 6.90 6.85 6.80 6.75 6.70

X

2706

.4

2672

.6

2684

.826

91.1

2701

.7

2718

.7

2876

.9

2893

.228

95.1

2914

.529

15.9

2928

.329

33.2

16 1C A chemiluminescent Wittig reaction product

Introduction

Chemiluminescence is a process whereby light is produced by an exothermic chemical

reaction instead of heat. Examples of chemiluminescence in Nature are the periodic flashes

of the male firefly and the glow of light produced by some organisms found in the deep of the

ocean. A firefly produces light by the reaction of luciferin with the enzyme luciferase,

adenosine triphosphate and molecular oxygen.

Commercial “light sticks” are also based on a chemiluminescent process. Compound 1C is a

highly fluorescent compound and an example of a typical fluorescer that changes the colour

of the actual chemiluminescent agent. Light sticks are not only used as toys or for

entertainment purposes, but also as emergency lights on life vests, as roadside markers,

underwater or night light sources that don’t require any batteries. They contain cyalumes

which are amongst the most efficient non-enzyme fluorescing substances known, with

fluorescence quantum efficiencies of up to 26%.

In the light-producing reaction, the cyalume gets hydrolysed by the attack of hydrogen

peroxide. The intermediate peroxyoxalate monoester is not stable and cyclises to 1,2-

dioxetanedione upon loss of trichlorophenol, a good leaving group.

H2O2O

O

O

O

Cl

Cl ClCl

ClCl

Cyalume orbis(2,4,6-trichlorophenyl) oxalate

O

O

O

OOH

Cl

ClCl

O

O

O

OOH

ClCl

Cl1,2-dioxetanedione

The high-energy 1,2-dioxetanedione is unstable and decomposes to two molecules of CO2. In

the presence of a fluorescer such as compound 1C it transmits its excess (strain) energy to 1C

whose fluorescence you will ultimately see.

O

O

O

O

1C 2 CO2 1C*

Excited state

hν

2 CO2 1C

Ground state Safety Notes

Benzyltriphenylphosphonium chloride: Causes skin and serious eye irritation; may cause respiratory irritation;

toxic in contact with skin; fatal if swallowed.

Anthracene-9-carbaldehyde: Not yet tested, treat as harmful.

Dichloromethane: Suspected of causing cancer. Do not inhale or ingest.

17

Sodium hydroxide: Very corrosive and causes severe burns; a 50% aqueous NaOH solution is extremely

damaging to eyes and skin — you must wear eye protection and gloves at all times; in case of contact with eyes, rinse

immediately with plenty of water and seek medical advice.

1-Propanol: Highly flammable liquid and vapour; causes serious eye damage; vapours may

cause drowsiness and dizziness.



Ethanol: Highly flammable liquid and vapour.

Bis(2-carbopentyloxy-3,5,6-trichlorophenyl) oxalate, bis[2-(methoxycarbonyl)phenyl] oxalate: Causes skin

irritation; causes eye irritation; may cause respiratory irritation.

Diethyl phthalate: No GHS symbol. Avoid contact with skin and eyes.

Sodium acetate: No GHS symbol.

Hydrogen peroxide: Harmful if swallowed; causes serious eye damage. Wear protective

gloves/protective clothing/eye protection. IF IN EYES: Rinse cautiously with water for several minutes. Remove contact

lenses, if present and easy to do. Continue rinsing.

Ph3P-CH2C6H5

Cl

NaOH

OH

1C

Anthracene-9-carbaldehydeC15H10O(206.24)

C25H22ClP(388.88)

(40.00)

CH2Cl2/H2O


Into a small round-bottomed flask place benzyltriphenylphosphonium chloride (0.97 g),

anthracene-9-carbaldehyde (0.515 g), dichloromethane (3 mL) and a small stirring bar. Clamp

the flask over a magnetic stirrer and stir the mixture vigorously while carefully adding 50%

aqueous hydroxide solution (1.3 mL) dropwise using a graduated plastic pipette. Continue

stirring for 30 minutes. Transfer the mixture to a small separatory funnel, remove the organic

layer and extract the aqueous layer once with dichloromethane (5 mL). Wash the combined

organic layers with brine, then dry over anhydrous CaCl2. Filter and evaporate the solvent on

a rotary evaporator. Recrystallise the crude product from 1-propanol.

In addition to the usual characterisation, take a UV-vis spectrum of your product in ethanol

18

(200 – 800 nm).7 Examine a dilute solution under an ultraviolet lamp. Check the purity of

your product by TLC (petroleum ether/ethyl acetate, 5:1).8

Chemiluminescence

Note: The chlorinated oxalate OX1 is quite expensive and should be used sparingly;

alternatively, use the non-chlorinated oxalate OX2. Work in pairs. Use your purest sample

of fluorescer 1C for this experiment.

Option 1: Mix the following reagents in a standard glass vial: diethyl phthalate (10 mL), your

product from Experiment 1C (3 mg), bis(2-carbopentyloxy-3,5,6-trichlorophenyl) oxalate

OX1 (75 mg) and sodium acetate (100 mg). Then add 30% hydrogen peroxide (0.2 mL) with

a plastic pipette, to initiate the reaction. Try cooling and warming the mixture after initial

mixing (using a cold/warm water bath).

Option 2: In a standard glass vial mix together the following reagents: ethyl acetate (5 mL),

your product from Experiment 1C (3 mg), bis[2-(methoxycarbonyl)phenyl] oxalate OX2 (100

mg) and sodium salicylate (15 mg). The chemiluminescence reaction will start upon addition

of one drop of 30% hydrogen peroxide with a plastic pipette.



7 Dissolve 1 mg of product in 20 mL of dry ethanol. No UV-Vis spectrophotometer can measure absorbances greater than 2 accurately, and therefore, if the longest wavelength absorbance turns out too high, take 2 mL of your solution and dilute by a factor of 2, 5 or 10 so that your maximum absorbance between 300 and 400 nm is about 1 to 1.5. (Make sure that you use absolute ethanol and not methylated spirits for making up your solutions. Why?) 8 Use a UV lamp to detect your TLC spots (it is always a good idea to check your TLC plate before running the TLC that there is enough UV-active compound on it).

19

(a) Analyse the spectroscopic data for your product. The 1H NMR spectrum is also available

through VISION. Suggest a structure for the product of your Wittig reaction, including its

stereochemistry.

(b) Compare the stereochemistry of your product with the “normal” cis/trans selectivity of the

Wittig reaction involving stabilised/non-stabilised ylides (Experiment 1B). Why is

anthracene-9-carbaldehyde much more selective than benzaldehyde? Hint: You will need to

use molecular models (or the interactive 3D models on VISION) for answering this question.

You might also find the following NMR chemical shift data useful for assigning the alkene

proton signals:

(c) Discuss your observations in the chemiluminescence experiment.

1.223.127.242.183.113.00

2187

.8

2090

.2

2106

.7

2312

.623

13.4

2320

.423

22.2

281.

6

2398

.12412

.2

2417

.7

2422

.0

2534

.4

8.5 8.4 8.3 8.2 8.1 8.0 7.9 7.8 7.7 7.6 7.5 7.4 7.3 7.2 7.1 7.0 6.9Chemical Shift (ppm)

20 1D Suzuki reaction

Safety Notes

Phenylboronic acid: Harmful if swallowed. In case of contact, carefully wash exposed parts of the body with

soap and water.

Bromobenzoic acid, iodobenzoic acid, reaction product: Harmful if swallowed; causes skin irritation;

may cause respiratory irritation; causes serious eye irritation.

Sodium carbonate: Causes serious eye irritation.

Palladium acetate/2-amino-4,6-dihydroxypyrimidine catalyst solution (0.25 mM in water): Causes serious

eye damage; avoid contact with skin and eyes.

Hydrochloric acid: Causes burns; irritating to the respiratory system.

Methylated spirits: Highly flammable liquid and vapour.

Pd(OAc)2

1DBOH

OH

C6H7BO2(121.93)

Br

C7H5IO2(248.02)

CO2H

N

NO

O

NH2

2

C7H5BrO2(201.02)

or

Na

Na

This reaction requires you to work on a small scale, just like students do in their final-year or

PhD research project. Use either the bromo- or iodobenzoic acid for this reaction.

Prepare a solution from phenylboronic acid (190 mg, 1.55 mmol), bromobenzoic acid (1.25

mmol), sodium carbonate (3.8 mmol) and water (8 mL). Stir until all components have

dissolved, then add the catalyst solution (0.5 mL) and heat to 70 °C for 30 min.

Leave to cool to room temperature, cool further with an ice bath and carefully acidify with

dilute HCl. Stir for 5 min once all the HCl has been added. Collect the solid and recrystallise

from a mixture of 2 mL of dilute HCl and the minimum amount of methylated spirits.

In addition to the standard characterisation, check the purity of your product by TLC

(methylated spirits) and record also a UV spectrum9 (200 – 400 nm).

9 Dissolve 1 mg of product in 20 mL of dry ethanol. No UV-Vis spectrophotometer can measure absorbances greater than 2 accurately, and therefore, if the longest wavelength absorbance turns out too high, take 2 mL of your solution and dilute by a factor of 2, 5 or 10 so that your maximum absorbance between 300 and 400 nm is about 1 to 1.5. (Make sure

21

Laboratory report


(a) Analyse the spectroscopic data for your product. The full NMR spectrum is also available

online on VISION.

(b) Formulate a detailed catalytic cycle illustrating the formation of the coupling product. Your

proposed mechanism should include:

i) oxidative addition,

ii) transmetallation,

iii) reductive elimination and regeneration of Pd(0) and

iv) a rationale for the amount of base used.

(c) Estimate the turnover10 by calculating the ratio of substrate to catalyst concentration.

(d) What are the benefits of performing the Suzuki reaction in aqueous solution? Compare your

procedure with the approach in the original reports of the Suzuki reaction.

that you use absolute ethanol and not methylated spirits for making up your solutions. Why?)

10 The turnover number (TON) is defined as the total number of moles of product produced per mole of catalyst.

13.5 13.0 12.5 12.0 11.5 11.0 10.5 10.0 9.5 9.0 8.5 8.0 7.5 7.0

8.00 7.90 7.80 7.70 7.60 7.50 7.40

Documents

Experiment 1 : The Wittig and Suzuki reaction - h. W · Experiment 1 : The Wittig and Suzuki reaction ... alkyl halide to give an ... In this lab you will prepare either a stabilised