MICHELLE HANKEL

Lab 1
Introduction to the Analytical Balance and
C a l i b r a t i o n o f Vo l u m e t r i c G l a s s w a r e
Experimental objective:
Synthesize a phenyl derivative of 3-aminopyridine by the Suzuki coupling reaction and characterization by
NMR
Introduction:
Organometallic complexes are used as catalysts in the industrial production of compounds such as
pharmaceuticals because they are inexpensive. These complexes are good catalysts for many reasons. One
reason is because the metal center of most of these complexes are capable of interacting reactant molecules.
Even if this interaction is minuscule, it can still increase the reactivity of the molecule greatly. Another
reason is because the metal center can also bring together two substrates and enhance the likelihood of
reaction between the substrates. Yet another reason is because a reactive intermediate may be stabilized
by the interaction to the metal center. This leads to a reduction of the activation barrier for the reaction
and facilitates the reaction between two substrates. The catalytic properties of organometallics are due to
the result of the central metal ions ability to change oxidation states and ligand environment in a reversible
manner. Ligands also influences these complexes catalytic ability. Choosing certain ligands may allow for
selectivity in a reaction. Suzuki found that many palladium(0) and palladium(II) compounds are great
catalysts.
Experimental:
In this experiment, we look at the coupling reaction between an arylboronic acid and an arylhalide in the
presence of a palladium-phosphine catalyst. Arylhalides react with arylboronic acid in presence of Pd(0)
and sodium carbonate to form diaryl compounds.

The Suzuki reaction proceeds by oxidative addition of the aromatic halide to the palladium(0) catalyst
which generates the palladium(II) intermediate. The intermediate then undergoes a trans-metallation
with the arylboronate, the product was expelledby reductive elimination, regenerating the palladium(0)
catalyst. Reagent grade chemicals and solvents were used. The 3N HCL and 6N NaOH were prepared by the
lab TA.
Part A
Balanced equation:

Reagents
3-amino-2-chloropyridine

phenylboronic acid

benzaldehyde

Molar Mass (g mol-1)

Mass Required

128.56
1.03g

121.93
1.232g

106.121
1.06

Moles mol

.008

.009

.01

Mole ratio req'd

Pre-Catalyst

Dichlorobis(triphenylphosphine)palladium(II)

Mass Required

20mg

Moles mmol

.28

Product
3-amino-2-phenylpyridine
Molar Mass (g mol-1)

170.211

Observed yield: .98g

Theoretical Yield: .008mol x 170.211g=1.36g
Percent Yield: .98g/1.36g x 100=72%
The limiting reagent in this synthesis is 3-amino-2-chloropyridine
Observations:
The reagents along with 20mL of toluene were added to a 100 mL round bottom flask equipped with a stir
bar. A condenser was added and closed with a septum. The mixture was stirred for 15 minutes at room
temperature. After 15 minutes 20 mg of dichlorobis(triphenylphosphine)palladium(II) as added and the
reaction mixture was stirred for an addition 15 minutes. A solution of sodium carbonate is created by
dissolving 1g in 20mL hot water which is then added to the reaction mixture. The solution is refluxed
overnight. The organic layer turns pink/red in color after approximately 30 minutes, but turned
yellow/brown at completion.
Part B
The reaction mixture is cooled to room temperature. Approximately .1g of Celite is added to the mixture
and it is then filtered and washed with toluene. The precipitate is discarded. The filtrate is placed into a
separatory funnel and allowed to separate into two layers. The aqueous bottom layer is drained and
discarded. The organic layer is washed with 20mL of DI water and the bottom layer is drained and
discarded again. 6mL of 3N HCl is added drop wise to the yellow/brown organic layer. The funnel is gently
shaken for 5-10 minutes. The two layers are allowed to separate. Our desired product is now in the bottom
aqueous layer. It is collected in a beaker and the organic layer is extracted again with another 20mL of
water. The organic layer is discarded. The aqueous layer we saved is put into a clean sep funnel and treated
with 20mL of diethyl ether. 5 mL of 6N NaOH is added and the sep funnel is swirled. As the aqueous layer
is basified the product migrates into the organic layer. The organic layer is saved and the aqueous layer is
extracted again with another 20mL of ether. The organic layer is treated with 2g of anhydrous magnesium
sulfate. The solution is filtered and reduced to a yellow oil by rotary evaporator.
First Extraction:

Second Extraction:

Third Extraction:

Discussion:
The percent yield was decent. Decrease in percent yield may have been caused by spillage or evaporation,
loss transferring between flasks, and during filtering. The experiment went smoothly and no problems
were experienced. The instructions in the lab manual were followed exact.. All reagent grade chemicals and
solvents were used. The glassware was thoroughly cleaned and dried before use. We weighed out or
reagents with extreme care, trying to get as close to the required amounts as possible. The NMRs were
obtained by Dr. Navamoney Arulsamy using the University of Wyomings Brukner Nuclear Magnetic
Resonance machine.
There are many advantages to Suzuki coupling reactions. They can very easily work up the reaction, no
TLC or column chromatography is needed. Only requires a separatory funnel which reduces time and
money required. The reactants are readily available, nontoxic, and air- and water-stable. They react
under mild
conditions and are amenable to a variety of reaction conditions, including the use of aqueous solvents and
substrate supports. The inorganic boron byproducts can be easily removed after completion of the
reaction. Most important of all, the coupling proceeds with high regio- and stereoselectivity, and islittle
affected by steric hindrance. It does not affect other functional groups in the molecule. The two types of
compounds necessary for Suzuki reactions are aromatic halides and aromatic boronic acids. The most
common bases used for this reaction are NaOH and sodium carbonate. Two common solvents used are
toluene and water.
In this reaction Dichlorobis(triphenylphosphine)palladium(II) is our precatalyst. Palladium center
converts between Pd(II) to Pd(0) and back to Pd(II). The active catalyst is palladium with 2triphenylphosphine. The amino group makes the reaction very slow, we activate the compound by adding
benzaldehyde and remove it by adding HCl into the solution.

1H

and 13C NMR

3-amino-2-phenylpyridine
The 1H NMR spectrum measured
contains seven groups, which is what we
expect to see. The peak at 8.1 ppm
appears to be a quartet, I attribute it to
the number four Hs. I believe the doublet
at 7.6ppm is due to the number one H. I
attribute H number two to be the triplet
at approximatelty 7.47ppm. I attribute
the peaks at 7.6 to the H number three. I
believe that the small peak at 7.26ppm is
due to H number seven. I believe the
peak at 3.8 is due to the number six
hydrogens.

For the C NMR, we expect to see nine different

peaks. The peak at 145.2 ppm is due to carbon
number five. The peak at 140.2 ppm is due to
carbon number one. The peak at 140.1 ppm is
due to carbon number four. The peak at
138.8ppm is due to carbon number six. The
peak at 128.9ppm is due to carbon number
nine. The peak at 128.6ppm is due to carbons
number eight. The peak at 128.3ppm is due to
carbons number seven. The peak at 123.2ppm
is due to carbon number two. The peak at
122.8ppm is due to carbon number three.

Questions:
1. What is the active catalyst? How is it produced?
The active catalyst is Pd(PPh3)2.

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PdCl2(PPh3)2 + PhB(OH)2 + Na2CO3 + H2O Pd(PPh3)2 + PhOH + H3BO3 + CO2 + 2NaCl
Phenylboronic acid is converted to the more reactive phenylborate by Na 2CO3. PhB(OH)2 and Na2CO3 are
reacted with PdCl2(PPh3)2 to create the active catalyst.
2. Write a detailed mechanism for the formation of the product accounting for all of the byproducts not
included in the equation above. Label each step in the mechanism.

3.What are the roles of sodium carbonate in the Suzuki coupling reaction? Formation of the palladium
complex, and acceleration of the reductive elimination step by reaction of the alkoxide with the palladium
complex.
4. Speculate what substituent instead of the chloride group in the substrate would lead to faster reaction?
Iodo and bromo are more reactive than chloride, so either or would make the reaction faster.
5.Which is more reactive: PhB(OH)2 or PhB(OH)2O-?
PhB(OH)2
6.Which of the substrates, 2-chloropyridine, 2-iodopyridine, 3-amino-2-iodopyridine or 3-amino-2chloropyridine is the most reactive in Suzuki coupling?

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Iodo, bromo more reactive than chloro. Amino group makes the entire compound less reactive. Due to this
I believe Iodopyridine would be the most reactive.

References:
1. Experiment 5. (2014). In Inorganic Chemistry Laboratory Manual. Copy and Print Center.