From the stoichiometry, it should be obvious that the sodium ethoxide is used in excess. Alkyl phenyl ethers are prepared by the williamson synthesis section 17. The elimination reaction occurs because the rearward approach that is needed for an s n 2 mechanism is impossible due. Williamson synthesis definition is a method of synthesizing ethers by reaction of a sodium alkoxide with a halogen derivative of a hydrocarbon as an alkyl halide. Cliffsnotes study guides are written by real teachers and professors, so no matter what youre studying, cliffsnotes can ease your homework headaches and help you score high on exams. The standard synthesis requires a 6070 minute reflux time frame to allow for this reaction to run until completion. Angela puchlopekdermenci, alpay dermenci, fan liu williamson ether synthesis r o r x r oh r or base myers co bondforming reactions. A reflux was preformred and the solution was placed in a sep funnel with aqueous layer being drained off. Williamson ether synthesis r o r x r oh r or base myers co bondforming reactions. The williamson ether synthesis is a common reaction in the field of organic chemistry in industrial synthesis and in undergraduate teaching laboratories. In this experiment, students will convert the acetaminophen the active ingredient in tylenol into phenacetin to exemplify a williamson ether synthesis. So even if you forgot the name of this reaction, you would still know what to do just by using the flow chart. Well, williamson ether synthesis is just the name for that specific route that you take on the flow chart.
The williamson ether synthesis can specifically be found in sections 172 and 182. To obtain the best yields of mixed dialkyl ethers, we select a 1. Permission reusing this file original work published in the public domain. The williamson ether synthesis is one of several organic chemistry reactions referred to as named reactions, which employ the name of the scientist who developed it. The mechanism begins with the base abstracting the proton from the alcohol to form an alkoxide intermediate. Formal enantioselective phenoxylation of keto esters. Williamson synthesis definition of williamson synthesis. The williamson ether synthesis is the easiest, and perhaps the fastest, way to create ethers. The williamson ether synthesis features these conditions and therefore can be used to illustrate this important reaction type. Because alcohols are weak acids, an alkoxide ion must be prepared using a strong base such as sodium hydride. Optimization of microwaveenhanced williamson ether. Williamson ether synthesis is a reaction that uses deprotonated alcohol and an organohalide to form an ether.
During step 1 of the mechanism, the reaction undergone is an acidbase reaction in which the alcohol is the acid. Lab 10 lab report lab 10 williamson ether synthesis. Yields for these ether syntheses are traditionally low when reaction times are shortened, which can be the. Williamson ether experiments are commonly performed by students in undergraduate organic chemistry instructional laboratory courses. Mechanism the williamson ether synthesis can be very useful and can apply to many compounds, but it has three primary limitations. Williamson ether synthesis request pdf researchgate. Synthesis of epoxides there are two common ways to make. Williamson ether synthesis with phenols at a tertiary stereogenic carbon. The williamson ether synthesis is an organic reaction used to convert an alcohol and an alkyl halide to an ether using a base such as naoh. A multioutcome experiment for the williamson ether synthesis. Alkoxides consist of the conjugate base of an alcohol and are comprised of an r group bonded to an oxygen atom. Williamson ether synthesis mechanism organic chemistry. Obtain 360 mg of acetaminophen and transfer into a dry 25ml roundbottom flask rbf. Files are available under licenses specified on their description page.
Add a stir bar, 560 mg of k 2co 3 ground if necessary, 6. In equations like this, the reagents over the arrow are added in a sequence of separate steps, not all at once. Pdf williamson ether synthesis nguyen hieu academia. Sn2 reactions chem 115 background the synthesis of ethyl ether from sodium ethoxide and ethyl iodide was first reported by alexander w. It may be practical for one tablet to be shared between two students. The williamson synthesis is the preferred laboratory method for making ethers. Williamson synthesis an overview sciencedirect topics. The synthesis of epoxides by base treatment of halohydrins is an example of an intramolecular. Functionalized allyl aryl ether synthesis from benzoic. Symmetrical ethers can be prepared by treating the corresponding alcohol with a strong acid limitations. Williamson ether synthesis an overview sciencedirect topics. Kazutaka shibatomi, manato kotozaki, nozomi sasaki, ikuhide fujisawa and seiji iwasa, cheminform abstract. The alkoxide then attacks the alkyl halide in a nucleophilic substitution reaction sn 2. Several examples of the williamson ether synthesis are given in the following equations.
This method cannot be used with tertiary alkyl halides, because the competing elimination reaction predominates. Week 1 510512 synthesis of phenacetin, williamson ether synthesis reaction set up. Sn2 reactions chem 115 background the synthesis of ethyl ether from sodium ethoxide and ethyl iodide was first reported by. Because alcohols are not highly acidic pka1618, the base chosen must be strong enough to deprotonate. The alkyl halides served as the unknown component of the experiment, and students were given these.
So if i add that alcohol in the first step, sodium hydride, i take off that proton, form an alkoxide, that alkoxide nucleophilic attacks the methyl iodide to add the methyl group on, and to form the ether on the right. Chem m52lbh52lb experiment 2 page 1 experiment 1 williamson ether synthesis of guaifenesin and isolation of an expectorant from cough tablets reading assignment. So thats how to think about using the williamson ether synthesis. The williamson ether synthesis is an s n 2 reaction in which an alkoxide ion is a nucleophile that displaces a halide ion from an alkyl halide to give an ether. Aug 18, 2015 kazutaka shibatomi, manato kotozaki, nozomi sasaki, ikuhide fujisawa and seiji iwasa, cheminform abstract. Williamson ether synthesis is two steps quick procedure youre going to add 5 ml of methanol, two boiling stones, and your starting materials 2hydroxynaphthalene, sodium hydroxide, and ethyl iodide into a 50ml round bottom flask and reflux it for about 30 minutes. Hindered dialkyl ether synthesis via electrogenerated. The williamson ether synthesis west virginia university. David rawn, in organic chemistry study guide, 2015. A strategy toward the preparation of substituted allyl aryl ethers from benzoic acids via a dearomatization and decarboxylative allylation dca reaction is presented. Experminet 5 synthesis and bromination of phenacetin. Williamson ether synthesis with phenols at a tertiary. The structure of ethers was proved due to this chemical reaction.
Jul 19, 2011 williamson ether synthesis is two steps quick procedure youre going to add 5 ml of methanol, two boiling stones, and your starting materials 2hydroxynaphthalene, sodium hydroxide, and ethyl iodide into a 50ml round bottom flask and reflux it for about 30 minutes. Show the combination of alcohols and haloalkane that can be best used to prepare each ether by williamson ether synthesis. In this multioutcome experiment, students were provided 4bromophenol and one of three alkyl halides. Obtain the mass of an extrastrength tylenol tablet. While students of organic chemistry are taught the williamson ether synthesis34 as a classic way to make primary alkyl ethers. Williamson ether synthesis organic chemistry video. To prepare a mixed ether, it is necessary to choose the proper combination of reagents. Media in category williamson ether synthesis the following 21 files are in this category, out of 21 total. The williamson ether synthesis proceeds via an s n 2 mechanism, in which an alkoxide ion displaces a halogen ion. Experiment 5 synthesis and bromination of phenacetin. Synthesize ethers through the williamson ether synthesis. One of the standard protocols for synthesizing both asymmetrical and symmetrical ethers is via the williamson ether synthesis.
Williamson ether synthesis reaction of metal alkoxides with alkyl halides or tosylates to give ethers. Week 1 synthesis of phenacetin, williamson ether synthesis reaction set up. Ethers are a class of organic compounds that contain an ether groupan oxygen atom connected to two alkyl or aryl groups. The name of the reaction was coined after alexander william williamson developed it in 1850. Williamson ether synthesis mechanism, uses, limitations. The reaction occurs with inversion of configuration at chiral centers and can be limited by possible competing elimination reactions. Williamson ether synthesis is a reaction that uses deprotonated alcohol and an organohalide. The formed ether is then reacted to 2allyl phenol using the claisen rearrangement. Introduction alcohols, ether, and epoxides are 3 functional groups that contain c.
Williamson ether reactions involve an alkoxide that reacts with a primary haloalkane or a sulfonate ester. Ethers bearing at least one tertiary carbon will follow a s n 1 mechanism, those with only primary or secondary carbon. The most versatile method for making ethers is the williamson ether synthesis, named for english chemist alexander williamson, who devised the method in the 19th century. General method for ether synthesis o h br alcohols can be easily deprotonated to form strong nucleophiles addition of the deprotonated alcohol alkoxide to an alkyl halide results in an sn2 reaction this method can be used to synthesize both symmetrical and unsymmetrical ethers since it is an sn2 reaction, it has the same limitations as any other.
The first step in this reaction is forming the conjugate base of the alcohol called an alcoxide by reacting the alcohol with sodium metal. Since alkoxides are strong bases, unhindered primary or methyl alkyl halides should be used since 2 halides will give predominant elimination and 3. Other articles where williamson ether synthesis is discussed. Electronic supporting information files are available without a subscription to. The alkyl halides served as the unknown component of the experiment, and students. In these reactions a phenoxide ion displaces a halide ion from a primary haloalkane. The reaction occurs with inversion of configuration at chiral centers and can be limited by possible competing elimination. The benzoic acids undergo a dearomatization to give alkylated 2,5cyclohexadienyl ketoesters which are subjected to a palladiumcatalyzed dca reaction, providing a variety of functionalized allyl aryl ethers. Overview of twostep synthesis of bromophenacetin from acetaminophen.
The williamson ether synthesis is a commonly used mechanistic route to ethers, because of its simplicity and its broad applicability to alcohols and alkyl halides. The williamson ether synthesis is an organic reaction, forming an ether from an alkyl halide and an alcohol. All structured data from the file and property namespaces is available under the creative commons cc0 license. Since alkoxides are strong bases, unhindered primary or methyl. Outline a synthesis of cyclopentyl methyl ether from cyclopentene. In equations like this, the reagents over the arrow are added in a sequence of separate. The general method for the synthesis of ether is williamson ether synthesis, involves nucleophilic displacement of a halide ion or other good leaving group by an alkoxide ion. An ether is prepared by treating an alkoxide with an alkyl halide.
In williamson ether synthesis, the alkoxide ion reacts with primary alkyl halides and tosylates to form ethers. Alternatively, cyclopentyl methyl ether may be synthesized from cyclopentene. Functionalized allyl aryl ether synthesis from benzoic acids. Williamson ether synthesis an overview sciencedirect. One of the most useful applications of phase transfer catalysis in nucleophilic substitution has been in the williamson ether synthesis. What links here related changes upload file special pages permanent link page. General method for ether synthesis o h o br alcohols can be easily deprotonated to form strong nucleophiles addition of the deprotonated alcohol alkoxide to an alkyl halide results in an sn2 reaction this method can be used to synthesize both symmetrical and unsymmetrical ethers since it is an sn2 reaction, it has the same limitations as any. This reaction was developed by alexander williamson in 1850. Request pdf williamson ether synthesis ether from the alkylation of alkoxides by alkyl halides. View enhanced pdf access article on wiley online library html view download pdf for offline viewing.
It uses an alkoxide ion to attack an alkyl halide, substituting the alkoxy. The williamson ether synthesis is a reaction that converts alcohols roh into ethers ror. Williamson ether synthesis usually takes place as an s n 2 reaction of a primary alkyl halide with an alkoxide ion. Optimization of microwaveenhanced williamson ether synthesis of. The same material will also be isolated from over the counter tablets via a simple extraction. The williamson ether synthesis is an organic reaction, forming an ether from an organohalide and a deprotonated alcohol.
Many of the reactions used in organic chemistry are described as being named reactions. Williamson ether synthesis usually takes place as an s n 2 reaction of. Dec 31, 2018 a strategy toward the preparation of substituted allyl aryl ethers from benzoic acids via a dearomatization and decarboxylative allylation dca reaction is presented. Arrange the following compounds in order of increasing solubility in water. In this experiment you will be using a simultaneous williamson ether synthesis of guaifenesin, a potent antitussive cough, and its extraction from an overthecounter cough tablet to illustrate the equivalence. This process is experimental and the keywords may be updated as the learning algorithm improves.
Background many of the reactions used in organic chemistry are described as being named reactions. The williamson ether synthesis is an organic reaction, forming an ether from an organohalide. The williamson ether synthesis is the most widely used method to produce ethers. Optimization of microwaveenhanced williamson ether synthesis. In the usual williamson synthesis of an ether, a primary alkyl halide reacts.
In this experiment, students will convert the acetaminophen from an extra strength tylenol tablet into phenacetin to exemplify a williamson ether synthesis. The fischer esterification reaction was a named reaction, referring to emil. The alkoxide ion is prepared by the reaction of an alcohol with a strong base such as sodium hydride. Typically it involves the reaction of an alkoxide ion with a primary alkyl halide via an s n 2 reaction. S n 2 pathway is required for the synthesis this reaction is useful only when the alkyl halide is primary or secondary. In this experiment, 3chloro1,2propanediol will be allowed to react with the conjugate base of guaicol 2methoxyphenol via an s n2 reaction to provide guaifenesin as a racemic mixture. Data were linear predicted in the second frequency domain to 360 files and then. Inorganic chemistry organic chemistry alkyl halide ether synthesis williamson ether these keywords were added by machine and not by the authors.
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