Suzuki+Reactions

Thomas Lewis Solyana phillips Chem Lab 243 Carol Higginbotham

5/17/11
__ Introduction: __ First published in 1979 by Akira Suzuki, the Suzuki reaction couples  boronic acids (containing an organic part) to halides. The reaction relies on a palladium catalyst such as tetrakis (triphenylphosphine)palladium  to effect part of the transformation. The palladium catalyst (more strictly a pre-catalyst) is 4-coordinate, and usually involves phosphine supporting groups. Many fundamental transformations involved in the synthesis of pharmaceutically significant compounds are achieved by Suzuki reactions. Preparation of OximidineII is a substance that exhibits selective cytotoxicity for oncogene transformed cells. The key step in the synthesis of Oximidine II is an intramolecular Suzuki reaction between a vinyl bromide and a potassium trifluroborate salt. A Suzuki reaction is the organic reaction of an aryl  - or vinyl  - boronic acid  with an aryl  - or vinyl  - halide  catalyzed by a palladium complex. It is widely used to synthesize poly- olefins , styrenes  , and substituted <span class="wiki_link_ext">biphenyls  , and has been extended to incorporate alkyl bromides. The reaction also works with <span class="wiki_link_ext">pseudohalides, such as <span class="wiki_link_ext">triflates  (OTf), instead of <span class="wiki_link_ext">halides. <span class="wiki_link_ext">Boronic esters and <span class="wiki_link_ext">organotrifluoroborate salts  may be used instead of boronic acids.

This intro paragraph appears to be cut-and-paste from the net. If you use the words or ideas of someone else you must cite the source.

**Relative reactivity**: **R2-I > R2-OTf > R2-Br >> R2-Cl**

<<http://www.chm.uri.edu/bdeboef/chm292/suzuki.pdf>>

This experiment illustrates that Suzuki reactions are often undertaken in an organic solvent with water as a co solvent. An inorganic base ( such as sodium, potassium, or cesium carbonate) is also commonly used. There is currently much active research in the area of “green chemistry” from a synthesis perspective, employing reaction conditions that are less deleterious to the enviorment than previous approaches. Most organometallic reactions ( e.g Grignard and Gilman reactions) do not lend themselves to aqueous conditions but it is possible to use pure water as the solvent for certain processes. This is significant for reactions creating new carbon to carbon pie bonds as these form the basis of organic synthesis. This reaction illustrates recent advantages made in improving the “greenness” of an industrially important synthetic method. Phenylboronic acid is coupled with 4-iodophenol in the presence of 10% palladium on carbon and potassium carbonate. These conditions afford facile preparation of biaryl product (4-phenylphenol) of the tye currently marketed as a non steroidal anti inflammatory drugs. These are two over the counter NSAIDs that you are likely familiar with are acetylsalicylic acid (aspirin) and ibuprofen.


 * __ Procedure: __**Division of Chemical Education www.ICE.DirCHED.org Vol. 85 No. 4 April 2008. Journal of Chemical Education"Greening Up" the Suzuki Reaction
 * // All student must wear safety googles and equipment and all procedures must be undertaken beneath the fumehood. //**

1) 1)In a 50-mL round-bottomed flask; phenylboronic acid (122 mg); potassium carbonate (415 mg); 4-iodophenol (220 mg);and water (10.0 mL – automatic delivery pipette) was mixed.1 mL of water to the supplied vial containing of 10% palladium on carbon (3 mg) was added to create a suspension. The suspension was combined to the reaction mixture. The mixture was placed under reflux (water condenser) for 30 minutes, using a sand bath as the heat source and maintaining rapid stirring. Some solid precipitated.



2) The flask was removed from the sand bath and allowed to cool down at room temperature.



3) 2.5ml of Aqueous HCl (2M) was added to the filtrate until acidic to litmus paper(ph2)

4) The crude solid (still containing catalyst) was collected by vacuum filtration (Hirsch funnel) and washed with water (10 mL). The collected solid was dissolved in 10 mL methanol and removed the Pd/C by gravity filtration.10 mL distilled water was added to the crude product dissolved in methanol, causing solid to precipitate.



5) The entire product was heated for 10 minutes.

6) When the completed dissolution occurred, the solution was allowed to cool down slowly at room temperature and then placed in an ice-bath. 7) The recrystallized product was collected by vacuum filtration (Hirsch funnel) and dried very thoroughly for a week.

__** Data: **__ Recrystallized product collected: 0.047g
 * * || Compound || GMW || Amount Added || mmol || mp (C) ||
 * C6HIBO2 || phenylboronic acid || 121.93 || 123mg || 1.00 || 216-219 ||
 * C6H5IO || 4-iodophenol || 220.01 || 224mg || 1.00 || 92-94 ||
 * crystals K2CO3. 3/2 H2O || potassium carbonate || 138.21 || 416mg || 3.00 || 891 ||
 * || 10% palladium carbonate || 106.42 || 3mg ||  ||   ||
 * || 2 M HCl || 36.46 || 2.5ml ||  ||   ||
 * || methanol || 32.04 || 10ml ||  || -98 ||

Product Melting point: 163.1C - 165.1C

IR spectrum:



__Atom economy__=MW of desired product / MW of all reactants 4-Phenyl-phenol:170.21 g/mol / Phenylboronic acid: 121.93g/mol + 4-iodophenol: 220.01 g/mol + potassium carbonate 138.21 g/mol =.3544 x 100 = 35%

__Theoretical Mass yield__ = 1mmol of 4-phenylphenol 0.17021g

__Fractional Yield__= actual yield/theoretical yield = 0.17021/0.047= 36% Actual 4-phenylphenol=Melting Point: 163 ºC

__**Conclusion:**__ In this lab experiment the Suzuki reaction was used with the presence of water in order to have a less harmful effects for the environment, which will be favorable for a greener chemistry experiment. The yield produced by this experiment was not as large as expected but the purity of the final product was reasonable considering the melting point range of 163.1C-165.1C was close to the actual 4-phenylphenol m.p of 163 C. One source of error, which would explain the small amount that was yielded, was when funneling of the final product some of the substance was drained through the filter and was never collected which would explain the lack of final product. The IR spectrum has a major peak at 3415.14 indicating an alcohol group, the peak is not a regular shape for an alcohol. However, this could be the result of a phenyl group; This was the only important peak found in the IR spectrum. This experiment explain Suzuki reactions very well and how they can be used to generate things that we use in our everyday life such as aspirin, as you take the time to look at the procedure you can physically see each reaction step and how the final product is made for IR spectrum and the melting point. This lab experiment help explain to its researchers how Suzuki reactions with the presence of water can generate less harmful products then experimented with in previous works and how important this reaction is to create useful aspects of our everyday life.

I would like to see more explanation of the infrared spectrum.