Introduction

The Suzuki- miyaura reaction, also called Suzuki coupling is a transition metal catalyzed reaction to

produce C-C bonds. It was first published in 1981 involving haloarenes and phenyboronic acid. The

Suzuki coupling is compared to stille coupling in that both the reactions have a similar reaction scope

and proceeds through similar mechanistic cycle. Stille reaction, like Suzuki coupling, form C-C bonds

between alkenyls and organotin alkynes. The Suzuki-Miyaura catalytic reaction proceeds via three steps

namely oxidative addition, transmetalation, then reductive elimination. The relative reactivity in the

oxidative addition decreases in the order I, OTf, Br, Cl. This step involves conversion of Pd (0) to Pd (2)

species. According to mechanistic studies oxidative addition involves four isomerization pathways

starting from the cis isomer to more stable Tran’s isomer. The transmetalation stage involves the

transfer of alkyl group from organoborane to palladium complex. Reductive elimination stems from the

cis complex hence the Trans complexes isomerizes to cis isomer. Palladium and nickel catalysts are

broadly employed in Suzuki reaction. For palladium catalyst, it comprises two sections: ligands and

precursors. To boost reactivity and stability, catalysts must develop to be electron rich as well as

spatially bulky, thus affording a high turnover number plus low loading.

Regarding separation and recycling of catalysts, individuals have developed polymer supported

heterogeneous catalysis systems for the Suzuki reaction. Such catalysis have a significant values both in

pharmaceutical plus industrial production following the merit of preventing contamination outside the

ligand residue in products. Ligands are designed with spatially bulky and electron-rich features as the

electron rich ligands can help in the oxidative addition phase. The spatially bulky structure however

increases a metal’s orbital overlapping thus enabling reductive elimination. Ligand can be categorized

into three groups (nitrogen ligands, phosphine ligands, and carbon ligands) based on the atom

coordinated with the metal. Of the three ligands groups, phosphine is the most common palladium

ligand in industry and laboratory. In Suzuki cross coupling, PPh3 was the first plus the commonly used
monodentate phosphine ligand. Other electron rich and bulky phosphine ligands were introduced in the

1990s based on dialkylbiaryl phosphine ligands’s frame skeleton. These ligands facilitated Pd –catalyzed

carbon-carbon, carbon-oxygen, and carbon-nitrogen bond forming processes, plus supporting ligands

for other reactions. Other monodentate phosphine ligands having specific structures like the

monodentate ferrocene phosphine ligand can promote Suzuki cross coupling effectively.

The steps in the Suzuki reaction catalytic cycle influence both stereo and regio- configuration of a

product. The alkyl and alkenyl halides oxidative addition retains configuration of the electrophile

substrate, but benzylic and allylic halides invert the geometry. Such step produces the cis complex that

isomerizes to the Trans complex. Both reductive elimination and transmetallation steps retain the sterio

and radiochemistry established in the first stage.

Br [NiCl2(PCy3)2](1 mol % catalyst),K3PO4 Het

N + (HO) 2 -Het N
N t - amyl alcohol, 80C, 60 mins N

The present experiment provided an opportunity to discuss topics related to organic chemistry. These

topics included and were not limited to the transition metal catalyzed reactions, the Suzuki coupling

mechanism, plus the heterocycles. It also proved an opportunity to address modern topics like

pharmaceutical researches well as the increasing need for green chemistry.

Rationale

The present experiment involves the nickel catalyzed Suzuki reaction to link aromatic fragments

containing heteroatoms. After completing this task, the learners will have familiarized themselves with

the need of green and sustainable chemistry. The use of analytical methods like the NMR spectroscopy

and column chromatography are employed to determine the reaction’s outcome.

Results
 Compound Molecular weight (g/mol) Mass (g)
5 –Bromopyridime 158.98 0.0994
NiCl2 (PCy3)2 640.5 0.0044

K3PO4 212.27 0.6152

Elements present in 5- C H O B N
bromopyridime
Mass of each element 47.12 5.27 31.38 7.07 9.16
Molecular weight of 12 1 16 10 14
elements
Moles (mass/m.wt ) 47.12/12 5.27/2 31.38/16 7.07/10 9.16/14
= 3.927 = 5.27 =3 = 0.707 = 0.6543
Moles (whole number) 6 8 3 1 1
Compound: C6H8O3BN (molecular weight = {(12*6) + (1*8) + (16*3) + (10 *1) + (14*1)} = 152

Mw Req. mass (g) Actual mass A0

(g/mol) (g)
5- bromopyrimidine 0.63 mmol 158.98 0.1002 0.0997 0.0997
NiCl2(PCy3)2 0.0063 mmol 690.46 0.0083 0.0045 0.0051
Unknown boronic acid B 240 mg 0.2400 0.24150
K3PO4 2.84 mmol 212.27 0.6028 0.6207
2-methyl -2- butanol 2.1 mL

Mass of flask : 74.2368g

Mass of flask + product: 75.1923

Mass of product (crude yield): 0.9955g

Mass of stiches + vial+ product: 74.4836 g

Mass of stiches: 0.1604g

Mass of flask: 74.2368g

Yield: 0.0868g = 36%

Discussion

The nickel catalyzed Suzuki reaction using green solvents is described herein. Efforts were made to

render the Trans formation ideal for undergraduate instructional experiments. Several heterocyclic

substrates as well as heterocyclic boronic acids were examined. The experiment control was

implemented in one term of the advanced undergraduate organic chemistry lecture as well as lab course

that consisted of learners majoring in biochemistry and chemistry. They were introduced to cross

coupling reacting like the Suzuki reaction along with the green chemistry. They read the lab manual

which contained experimental details plus background information on green chemistry, cross coupling

as well as heterocycles. The learners completed the prelab work sheet which was made to enable them

comprehend the chemistry, experimental control, plus safety considerations. Completing the prelab to

satisfactory was a mandate for the learners to proceed with the experiment. The leaners were provided

with unknown boronic acid to perform the Suzuki reaction. The primary aspect of this experiment was

reaction set up, monitoring purification, as well as spectroscopic analysis. After carrying out the

experiment, it was easier to isolate the desired product after chromatography. Here, the NMR analysis

was employed to determine the unknown boronic acids including their cross coupled product.

Yields……………………………………..

Loss of product in during the experiment or purification are the primary reasons for the lower yield of

the product. Residual solvent was witnessed in multiple scenarios during the NMR analysis of the

product. Other notable impurities like the unreacted boronic acid were rarely noticed. A post lab

worksheet was employed to help in data analysis as well as further develop on the primary chemical
concepts from this work. Students were exposed to experimental control in the lab where they gained

experience in different methods plus techniques. This included and not limited to reaction set up on a

small scale, reaction analysis using TLC or thin layer chromatography, column chromatography, and

NMR analysis.

Conclusion

A modern protocol suitable for use in the undergraduate instructional lab was developed for the Suzuki

reaction. This experiment’s method was not only straight forward but also exposed biochemist students

to different topics in organic chemistry such as the transition metal catalyzed reactions, the need for

heterocycles in drug recovery as well as green chemistry. The experiment will also enable educators

introduce multiple topics into the undergraduate organic chemistry curriculum, which is often neglected

in the modern undergraduate organic chemistry labs.

Appendices

1. NMR spectrum of the unknown compound

2. TLC chart of the unknown compound