Nicholas Johnson Drawer #: U24A TA: Mathew Fields 3-19-2011 Williamson Synthesis Purpose: The purpose of this lab

was to become familiar with Williamson Synthesis and, therefore, gain experience with the process of preparing ethers via reactions between alkyl halides and substituted phenoxide anions. Also, this lab also aims to teach the effect of a catalyst in a chemical reaction. Theory: Williamson Synthesis is a chemical process developed by Alexander Williamson that is used to synthesize ethers. Ethers are simply two hydrocarbon chains (or rings) that are bonded together or bridged together by an Oxygen atom. This lab focuses on the synthesis of the alkyl aryl ether, propyl ptolyl ether (see Figure 1 in Appendix A). In order to explain how propyl p-tolyl ether is created in this lab, one must first understand the mechanics of a Williamson reaction. Upon examining the Williamson reaction in Figure 2 in Appendix A, one can see that this reaction involves the introduction of an alkoxide ion to an alkyl halide. The alkoxide ion is easily produced from the ions conjugate acid, which is simply an alcohol or phenol. In this lab, p-cresol is treated with NaOH to produce a compound that dissociates in water to produce a deprotonated p-cresol ion (see Figure 3 in Appendix A). This ion will behave as nucleophile, and will react with the electrophilic propyl iodide. However, in order for this reaction to occur, both the p-cresol and the propyl iodide must be suspended in a solvent that they are both soluble in. This presents a problem, as propyl iodide is insoluble in water, but soluble in organic solvents. Conversely, p-cresol is soluble in water, yet insoluble in organic solvents. This is solved with the addition of the phase catalyst, tetrabutylammonium bromide, which acts as a bridge by reacting with the p-cresol anion and carrying it into an organic phase, thus allowing for an electrophile-nucleophile reaction with the propyl cation. Once the two reagents have reacted within the organic layer, there will still exist some impurities in the mixture. In order to extract the propyl p-tolyl ether, a series of distillations must be performed. By adding diethyl ether to the initial aqueous phase, another organic phase is formed. This phase is added to the initial organic phase and the mixture of the two organic phases is treated with NaOH and in a series of two distillations to allow for optimal purity. Once the purified organic phase is yielded, it is heated at (35-40)C to boil out any remaining impurities. Once boiling ceases, the organic phase is further purified by being filtered through which removes any excess in the phase and also through which removes any remaining polar impurities in the phase. Finally, the filtered organic phase in then heated again, but this time at (60-65)C. The phase is heated until the boiling stops, to insure that all impurities are completely boiled out of the mixture. The remaining product will be propyl p-tolyl ether.

Results: Table 1: Values Used in Determining Limiting Reagents

Compound Molecular Mass (g/mol) Mass Used / Produced (g) Moles Used / Produced (mol) (Moles Used / Produced)(Ratio #) Expected Amount in Reaction/Expected Yield (mol) p-Cresol 108.2 .828 .00765 .00765 6M NaOH 28.1 2.769 .09854 .09854 Tetrabutylammonium Bromide 322.4 .091 .00028 .00028 Propyl Iodide 170.0 1.310 .00771 .00771 Propyl pTolyl Ether 150.2 .780 .00519 .00519

.00765

.00765

.00765

.00765

.00765

For Moles of p-Cresol Used:

For Moles of 6M NaOH Used:

For Moles of Tetrabutylammonium Bromide Used:

For Moles of Propyl Iodide Used:

For Moles of Propyl p-Tolyl Ether Produced:

For Determining Limiting Reagent: The reaction involved in this lab, shown in Figure 2 of Appendix A, is seen to have a mole ratio of 1:1:1:1:1. This would lead one to believe that tetrabutylammonium bromide is the limiting reagent, as it is present in the smallest amount of moles. However, because tetrabutylammonium bromide is a catalyst, it is present in both the beginning and the end of the reaction in, theoretically, equivalent amounts. Therefore, the tetrabutylammonium cation and the bromide anion are considered spectator ions, and cannot be considered limiting reagents, as they are unchanged in the net ionic reaction. Therefore, because p-Cresol has the next lowest mole ratio number, and is not comprised of spectator ions, we can conclude that p-Cresol is the limiting reagent. For Determining Percent Yield of Propyl p-Tolyl Ether: The general equation for Percent Yield is ( So, the Percent Yield of Propyl p-Tolyl Ether is calculated as follows: ( Analyzing the IR: When viewing the resulting IR spectrograph in Appendix B, the following peaks are seen to occur in the ranges pertaining to (3300 2800) , (3100 3000) , and (1150 1050) respectively: Important Peaks ( 2963.54 ) 2936.15 2876.94 1111.08 1068.64 1049.52 ) )

Discussion: As in any experiment, error played a role in the final results of the lab. One of the strongest pieces of evidence that supports the existence of error is that the percent yield came out to be 67.84% and not 100%. This occurrence can be explained by considering all the possible ways the final product could have been lost through the experimental procedure. First, while the perifilm prevented too much evaporation, some of the solution could have been lost through evaporation. Second, with all of the phase separations involved in this lab, some of the solutions were lost and/or mixed together in the pipetting process. This would cause impurities and/or shortages in solutions, thus causing error in the final yield of the product. Furthermore, the filtering processes involving and could have caused some of the product to be lost by not making it all the way through the pipet. Finally, some of the product could have been lost in the boiling process, provided the heat setting was slightly too high for even a very short period of time. While all of these reasons pose as possible error sources, they all can be prevented the same way. By paying very close attention to detail and performing each and every step in the experimental process, laboratory error can be kept at a minimal level. When considering the IR spectrograph shown in Appendix B, the results are rather pleasing. The resulting graph is almost identical to that of propyl p-tolyl ether. All of the important peaks (specifically

the peaks at 2963.54, 2936.15, 2876.94, 1111.08, 1068.64, and 1049.52 ) match up to represent an ether with aromatic and alkyl components, which is exactly what propyl p-tolyl ether is comprised of. Therefore, one can conclude that from the IR spectrograph, the resulting product, although some was lost through the experiment, was rather pure.

Conclusion: In conclusion, this lab accomplished its initial purpose of offering experience with the chemical process of Williamson Synthesis, limiting reagents, and percent yield. This lab also proved successful by producing an IR spectrograph with very high similarity to that of the IR spectrograph of propyl p-tolyl ether. Areas such as the filtration process and the heating could have been performed more carefully to produce even more desirable results. Also, if Gas Chromatography could have been used in order to test solutions for purity, it would have been easier to know whether or not to continue heating or to further filter the solutions used throughout the experiment. Nevertheless, this lab proved to be successful in teaching all it set out to teach by allowing for a hands-on approach to the fascinating technique of Williamson Synthesis. Waste Disposal: For this experiment, the following procedures for waste disposal were followed to ensure proper safety throughout the lab: 1. All equipment that came in contact with organic liquid was adequately rinsed with acetone and drained into the Organic Waste Disposal receptacle. The equipment was then rinsed with distilled water in the sink and dried. 2. All broken glassware was disposed of in the Broken Glass receptacle 3. All solid waste materials were disposed of in the Solid Waste receptacle 4. At the end of the lab, gloves used during the experiment were washed with acetone over the Organic Waste Disposal receptacle and then rinsed with distilled water in the sink. Once dried, the gloves were disposed of in the general waste basket. 5. All excess HCL and NaOH was disposed of in the Acids and Bases receptacle 6. All NaCl plates were cleaned with or (remember, DO NOT clean NaCl plates with ) References: Mayo, Dana W., Ronald M. Pike, and David C. Forbes. Microscale Organic Laboratory: with Multistep and Multiscale Syntheses. Hoboken, NJ: J. Wiley & Sons, 2011.

Appendix A:

Figure 1

The structure of Propyl p-Tolyl Ether

Figure 2

The Williamson reaction of p-Cresol and Propyl Iodide, treated with Sodium Hydroxide and Tetrabutylammonium Bromide to produce Propyl p-Tolyl Ether

Figure 3

The structure of the deprotonated p-Cresol anion (nucleophile)

Appendix B: (See attached IR Spectrograph)