{"id":8611,"date":"2014-11-07T17:51:58","date_gmt":"2014-11-07T22:51:58","guid":{"rendered":"https:\/\/www.masterorganicchemistry.com\/?p=8611"},"modified":"2026-05-07T06:31:14","modified_gmt":"2026-05-07T11:31:14","slug":"synthesis-of-ethers-2-back-to-the-future","status":"publish","type":"post","link":"https:\/\/www.masterorganicchemistry.com\/2014\/11\/07\/synthesis-of-ethers-2-back-to-the-future\/","title":{"rendered":"Ethers From Alkenes, Tertiary Alkyl Halides and Alkoxymercuration"},"content":{"rendered":"

When The Williamson Doesn’t Work: Synthesis of Tertiary Ethers From Alkenes, SN1 Reactions, and\u00a0 Alkoxymercuration<\/strong><\/p>\n

In the last two posts<\/a> we’ve been discussing the Williamson synthesis of ethers. As we saw, our discussion was essentially a\u00a0complete re-hash of everything we’d already said about the SN<\/sub>2 reaction that was covered awhile back.<\/p>\n

That’s the fun* thing about organic chemistry – things you learn in the early stages of the course often come back in different forms later in the course. (*your definition of “fun” may vary)<\/em><\/span><\/p>\n

Today’s post is similar in that we’re just going to be going back to old reactions we’ve already seen and look at them in a new light.<\/p>\n

In this post, we’ll cover making ethers via SN<\/sub>1 reactions and also through oxymercuration.<\/p>\n

\"summary<\/a><\/p>\n

Table of\u00a0 Contents<\/strong><\/p>\n

    \n
  1. How To Make Ethers of Tertiary Alcohols When The Williamson (SN<\/sub>2) Isn’t An Option?<\/a><\/li>\n
  2. Synthesis of Ethers via SN1 Reactions<\/a><\/li>\n
  3. Three Examples of Ether Formation Involving Addition of a Tertiary\u00a0 Alcohol To A Carbocation<\/a><\/li>\n
  4. Avoiding Carbocation Rearrangements With Alkoxymercuration<\/a><\/li>\n
  5. Summary: Synthesis of\u00a0 Ethers via SN1 (and related) Reactions<\/a><\/li>\n
  6. Quiz Yourself!<\/a><\/li>\n
  7. (Advanced) References and Further Reading<\/a><\/li>\n<\/ol>\n
    \n

    <\/a>1. How To Make Ethers of Tertiary Alcohols When The Williamson (SN<\/sub>2)\u00a0 Isn’t An Option?<\/h2>\n

    We ended the last post by posing a question. \u00a0How do we synthesize ethers like this one below (di-t<\/em>-butyl ether) ?<\/p>\n

    We saw that when we attempt to form ethers like this through a Williamson reaction, it fails miserably – giving us elimination products (via an E2) rather than the desired ether. (See article: Williamson Ether Synthesis<\/a><\/em>)<\/p>\n

    \"how<\/p>\n

    Let’s think about this for a second. Back when we covered substitution reactions, we learned that the SN<\/sub>2 was best for primary alkyl halides and poorest for tertiary alkyl halides, due to steric hindrance. (See post: The SN<\/sub>1 Mechanism<\/em>)<\/p>\n

    But there was a different substitution reaction we learned that was actually superior for tertiary alkyl halides versus primary alkyl halides – the SN<\/sub>1 – and it had to do with the greater stability<\/strong> of tertiary<\/strong> carbocations<\/strong> versus secondary versus primary carbocations. (See post: The SN<\/sub>1 Mechanism<\/a><\/em>)<\/p>\n

    \"ether<\/p>\n

    <\/a>2. Synthesis of Ethers via Reactions of Alcohols With Alkenes or Alkyl Halides<\/h2>\n

    In fact, we encountered carbocations not only in SN<\/sub>1 reactions but in another type of reaction as well. If we take an alkene and add acid, recall that we end up forming a new C-H bond on the least substituted carbon of the alkene and we form a carbocation on the more substituted carbon of the alkene (remember Markovnikov’s rule?). (See article: Markovnikov’s Rule<\/a>)<\/em><\/p>\n

    This might get you to thinking – can we use either of these reactions to form ethers, via a carbocation intermediate?<\/p>\n

    Sure!<\/p>\n

    \"taking<\/p>\n

    We can form this carbocation two ways.<\/p>\n

    If we dissolve an alkyl halide in the appropriate alcohol solvent, eventually the leaving group will leave, forming the carbocation<\/strong> – which is then trapped by the alcohol solvent<\/strong>. After removal of a proton, we’re left with our ether<\/strong>. This is a classic SN<\/sub>1 reaction.<\/p>\n

    Alternatively, if we start with an alkene in an appropriate alcohol solvent, and treat\u00a0with a strong acid – ideally a strong acid with a poorly nucleophilic counter ion [ yes to H2<\/sub>SO4<\/sub> and TsOH as acids, generally no to HCl, HBr, and HI<\/span>]<\/em> the carbocation will likewise be generated, which is then trapped via the same pathway as before.<\/p>\n

    <\/a>3. Three Examples Of\u00a0 Ether Formation Involving Addition Of\u00a0 an Alcohol To A Tertiary\u00a0 Carbocation<\/h2>\n

    Let’s look at three examples. The first one is a typical SN<\/sub>1 reaction<\/strong>. The second one is an alkene addition<\/strong> reaction. The third one is alkene addition… with a twist!<\/p>\n

    \"examples<\/p>\n

    [Note – I didn’t put the mechanisms of these reactions in because we’ve talked about these mechanisms so many times before. <\/em><\/span>To see them,\u00a0 hover here<\/a> or click this link<\/a>.<\/p>\n

    \u00a0<\/a><\/em><\/span>click here to see the mechanism of these three reactions<\/a><\/em><\/span>]\u00a0<\/strong><\/p>\n

    <\/a>4. Avoiding Carbocation Rearrangements By Using Alkoxymercuration<\/h2>\n

    “Oh yes”, you might be saying at this point, like someone who suddenly finds themselves awkwardly face-to-face with an old ex-boyfriend or ex-girlfriend. “Rearrangements.”\u00a0<\/em>Yes, rearrangements again!<\/p>\n

    Anytime we deal with carbocation intermediates, rearrangements are going to be something to watch out for<\/strong>. If we form, for example, a secondary carbocation adjacent to a tertiary or quaternary carbon, expect a hydride or alkyl shift (respectively) that will result in a more stable carbocation.<\/p>\n

    There is, however, a way out!<\/p>\n

    In particular, there’s a way we can form ethers from alkenes in a way that doesn’t involve a carbocation intermediate<\/strong>. It’s also a reaction we’ve seen before: oxymercuration.\u00a0<\/strong>(See post: The Three-Membered Ring Pathway<\/a><\/em>)<\/p>\n

    Oxymercuration involves dissolving the starting alkene in an alcohol solvent and adding a source of mercury(II) like Hg(OAc)2<\/sub> . A “mercurinium” ion is formed, which is then attacked at the most substituted position by one of the molecules of alcohol solvent.<\/p>\n

    After removal of a proton, we’re left with the product of “oxymercuration”. The mercury can then be removed by treatment with sodium borohydride (NaBH4<\/sub>). We often don’t cover the mechanism, but if you’re curious, hover here<\/a> or click this link<\/a>. <\/span><\/p>\n

    \u00a0<\/a><\/p>\n

    \"ether<\/p>\n

    Note that we’ve succeeded in adding “CH3<\/sub>OH” in this example across the alkene without any rearrangement occurring.<\/p>\n

    <\/a>5. Summary:\u00a0 Synthesis of Ethers Through SN1 (And Related) Reactions<\/h2>\n

    To summarize, we’ve revisited three methods today for ether synthesis:<\/p>\n