Williamson ether synthesis at the basic leave is rooted in the conditions of an SN2 reaction. However, students still struggle with the content. I have found myself trying to remind my class of the basics. I am quite fond of the Karty text, and have tried to compliment the book mechanics with some organically-flavored A B C’s.
A stands for alkyl group on the halide. Since the Williamson ether synthesis is a glorified bimolecular nucleophilic substitution. In SN2, the alkyl halides favored are small or unbranched. The rate of a Williamson ether synthesis decreases as you move from methyl halides to secondary halides. Tertiary halides will not undergo SN2.
When I talk about this point, I compare aliphatic halides to aryl halides to demonstrate that SN2 reactions will occur with sp3 hybridized alkyl halides.
B stands for bulk. Bulk can dictate if the reaction proceeds via substitution (SN2) or elimination (E1 or E2). Nucleophiles react fast with the alkyl halide when unbranched, but nucleophiles can work as easily when it has some bulk (ie. branching).
Bulk on the alkyl halides can cause the reaction to have substitution and elimination compete against each other. This almost reinforces the comments assigned to A. Little to no branching with a small nucleophile can give a large percentage of substitution product, the intended ether. However, the concern comes when there is bulk on both the nucleophile and alkyl halide. A bulky or branched alcohol, which is transformed into the nucleophile, can interact with a branched alkyl halide to give the byproduct of an alkene. The bulky nucleophile acts like a base and promotes the elimination pathway. This is when I make the statement that size matters.
That being said, if the Williamson ether synthesis is a glorified bimolecular nucleophilic substitution, the alkyl halides favored need to be small or unbranched. The nucleophile should have some bulk, if it is necessary.
C stands for a concerted pathway. Students should be aware of the competition between SN1 and SN2. The Williamson ether synthesis is a SN2. To show a comparison, the Karty text shows the synthesis of ethers with catalytic acid, which occurs through a stepwise process (SN1 mechanism).
Viewing the content from the student perspective can support them along their studies. Breaking a tough topic down into bulleted points can transition content from short term to long term memory. This thought can be expanded into bigger ideas in the chapters to follow by looking at the movements at each step….finding the nucleophile and electrophile, then applying the thought into a mechanism of negative to positive. Thus, we, as instructors, can make challenging content into achievable nuggets of knowledge.
-Kerri Taylor, Columbus State University
Feel free to share your thoughts in the “Comments” section below!
