Palladium Catalysis the Suzuki Reaction free essay sample

This step cannot occur in the absence of base and the exact mechanism have not been stated. 2 Boron â€Å"ate† complexes ,via forming a quaternization of the boron with a negatively charged base, are mostly frequent seen explanation. 3 An isomerization from trans complex to cis complex is required before the reductive elimination can undergo. The reductive elimination is the final step which gives the desired product and also reproduces the palladium catalyst. The regenerated palladium catalyst would participate in the reaction again to synthesize more products. In experiment, a ligandless palladium catalyst, Pd/C was used which is easier to handle and can be remove by simple filtration. The generalized catalytic cycle shown above is specific to palladium catalyst with ligand, such as triphenylphosphine. The procedure in this experiment could be applied to cross-coupling Suzuki reation of a variety of iodophenols and arylboronic acids, giving the corresponding hydroxybiphenyls . In many cases, the coupling products are obtained quantitatively. We will write a custom essay sample on Palladium Catalysis: the Suzuki Reaction or any similar topic specifically for you Do Not WasteYour Time HIRE WRITER Only 13.90 / page 3 Experiment Modifications were applied in the experiments. The filter paper was washed by 5mL of methanol and transferred the solution into 25mL Erlenmeyer flask since there was a little amount of crude product collected by suction filtration. 5mL of water was added to the solution instead of 10mL. There was no solid left in the flask before heating the solution on steam bath. The flask containing reaction solution was heated on the hot plate to evaporate the excess of methanol after it was cooling in the ice-bath. Due to limit of time, the flask was placed into the fume hood for one week after a few minutes of heating. The final product was obtained after one-week-long methanol evaporating process. Filtered the reaction mixture by suction, a white/greyish solid was collected in the filter paper. Recrystallized this solid, white solids were obtained with a close melting point to that of final product. The NMR spectrum of this solid also showed the aromatic peaks. This solid was suggested as an intermediate of reaction, mostly likely ArOH-Pd-Ar in reductive elimination. Since a ligandless palladium catalyst was used in this reaction, a transformation from trans complex to required cis complecx was unnecessary. The unreacted intermediate may be left on the filter paper. This complex contained two phenyl groups which gave the aromatic peak in NMR spectrum. Because of the presence of the palladium catalyst, this complex cannot be soluble in the reaction solution and precipitate on the filter paper. Due to similar structure and functional groups presented, its measured melting point was close to that of the final product. When added 2M HCl into the filtrate until the entire solution was acidic, white cotton-like product was generated at the bottom of the beaker. A few minutes later, this product turned to be slight tan color. Since the reaction was performed in a basic aqueous media, the reaction was quenched by acidification with diluted HCl to precipitate the coupling product. Filtration would give the crude yield of product. At the beginning of the filtration, white product was collected on the filter paper; however the solid became less and less when adding more acidified filtrate, and washed the product with 10mL of water, only small amount of product was left on the filter paper. This unexpected situation stated that most of the products synthesized were actually soluble in water which was disagreed that the biphenyl-4-ol is insoluble in water. It was also the first indication of undesired product synthesized. Modifications were applied to recrystallization. 5mL methanol was used to wash off the products left on the filter paper. There was no solid precipitated when added 5mL of water into the flask containing reaction solution. When cooled the reaction solution in ice bath after heating on steam bath, there was no product was crystallized. The cooled solution reheated on the steam bath to evaporate excess of methanol. This evaporating process lasted for one week in the fume hood due to limit of time. Backed to the lab, wet product was obtained in the bottom and wall of the flask. The appearance of the product was slight red and mixed with some small spots of white solids. Due to the wetness of product, the melting point was unable to be measured directly. 2mL of methanol was added to the flask which was prepared for further recrystallization process. Since all the products dissolved in the methanol, the reaction solution was heated on the hot plate to evaporate the methanol. The product was regenerated, however, the red color turned to be darker and the white spot tended to show tan color. The appearance of experimental product was totally different from expected light tan color, which was second indicator of undesired product synthesized instead of biphenyl-4-ol. The measured melting point of this product was higher than literature value, which indicated the presence of impurities. Also, it was the third evidence of undesired product synthesized. The yield of product was only 11. 94% that was significant lower than high efficient yield from literature. This low yield was resulted from many aspects. The reaction condition in literature is halophenol (1mmol), phenylboronic aicd (1mmol), potassium carbonate (3mmol), Pd/C (3mg, 0. 3mol%) in 10mL of water at 50? for 12 hours, giving great than 99% yield. 3 Sakural et al3, they also demonstrates that when 0. 3mol% of Pd/C supended in aqueous potassium carbonate solution, was treated with stoichiometric amounts of 3-iodophenol and phenyboronic acid, the yield of 3-hydroxybiphenyl were 30%, 64%, 88%, 97% and 97% with quenching after 3, 6, 9, 12 and 24 hours. From their works, the reaction time plays an important role in yielding. Since limit of time during our experiment, the acidification was directly followed the second suction filtration. Insufficient reaction time gave the relatively low yield of our product. Since the yield of product was significant low, the amount of methanol added according to the lab manual was always excess, which became a barrier for the products to be precipitated from reaction solution. Thus, the evaporation process of methanol lasted for one-week-long. To improve this experiment, a longer reaction should be considered. As mentioned before, the experimental produce may not be the desired biphenyl-4-ol. It can be proved by the appearance of the product and deviation of measure melting point. Since there were no reagents or intermediate showing red color, the identification of the final product required further detection, such as chromatography, mass relationship and NMR spectrometry. Possible deviation may arise from improper operation and side product in the reaction. The possible side products would not be discussed here since it was beyond current level of knowledge. The Suzuki reaction is important in organic chemistry since it can achieve a numerous of organic transformation. It has some general advantages: can be conducted under mild reaction condition; can use common organoboronic acids; inorganic by-products are easily removed from reaction mixture,;it is stereoslective reaction; it is less toxic than other competitive method (since boronic acid are environmentally safer and less toxic than organostannanes, in our case, the palladium-charcoal is a ligandless catalyst which is convenient and environmentally friendly); the reaction can take place in the presence of other functional groups (which means protecting group is not always necessary). Even the Sukuzi cross coupling is versatile, there are still some shortcomings: aryl chlorides react slowly; sp3-hybridized alkyl halides sometimes show no reactivity; in the absence of the base, multiple side reactions are possible. 3 Other kind of palladium-catalyzed cross coupling reactions, such as the Stille cross-coupling, Kumada coupling, Sonogashira coupling and the Heck reaction are also important in organic transformation. Here are some vital synthetic applications: synthesis of Myxalamide A which is observed to have antibiotic and antifungal activity; synthesis of Oximidine II which is highly biologically active and affect the cell cycle at G1 Phase; and synthesis of KDR Kinase Inhibitor which inhibits the activity of specific tyrosine kinase enzyme in the body. 2 Conclusion During this experiment, a palladium-charcoal catalyzed Suzuki cross coupling was performed using phenylboronic acid, p-iodophenol and potassium carbonate in water.