{"id":9339,"date":"2015-12-16T07:00:36","date_gmt":"2015-12-16T12:00:36","guid":{"rendered":"https:\/\/www.masterorganicchemistry.com\/?p=9339"},"modified":"2026-05-07T06:13:25","modified_gmt":"2026-05-07T11:13:25","slug":"protecting-groups-in-grignard-reactions","status":"publish","type":"post","link":"https:\/\/www.masterorganicchemistry.com\/2015\/12\/16\/protecting-groups-in-grignard-reactions\/","title":{"rendered":"Protecting Groups In Grignard Reactions"},"content":{"rendered":"

Using Protecting Groups In The Formation of Grignard Reagents<\/strong><\/p>\n

Now that we’ve gone over the most useful reactions of Grignard reagents – addition to epoxides, aldehydes, ketones, and esters – let’s go back to the topic of how to\u00a0make<\/strong> Grignard reagents, albeit with a twist.<\/p>\n

Here’s the summary for today’s post:<\/p>\n

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

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

    \n
  1. Yet Another Way To Screw Up The Formation of Grignard Reagents<\/a><\/li>\n
  2. “Protecting Groups” Mask A Group From Attack<\/a><\/li>\n
  3. Acetals As A Protecting Group For Aldehydes And Ketones<\/a><\/li>\n
  4. How To Use Grignards With Protecting Groups: An Example<\/a><\/li>\n
  5. Summary: Grignards And Protecting Groups<\/a><\/li>\n
  6. Notes<\/a><\/li>\n
  7. Quiz Yourself!<\/a><\/li>\n<\/ol>\n
    \n

    <\/a>1. Introducing Yet Another Way To Royally Screw Up Making A Grignard Reagent<\/strong><\/h2>\n

    In a previous post we said that there are cases where making Grignard reagents can fail due to the presence of an acidic proton. Like this example.<\/p>\n

    \"failure<\/p>\n

    The problem here is that Grignard reagents are strong bases, and will react with even weak acids (like alcohols). If we try to make a Grignard on a molecule with an acidic functional group, we’ll end up destroying our Grignard instead.<\/p>\n

    We saw that one way around this problem was to protect alcohols as some kind of inert functional group (like an ether) which doesn’t react with our Grignard.<\/p>\n

    Similarly, there are other cases of molecules where making a Grignard reagent will fail for similar reasons. For example: why does this reaction\u00a0not<\/strong> give the desired Grignard reagent?<\/p>\n

    \"failure<\/p>\n

    The problem here, as you might have guessed if you read the last post, is that\u00a0this Grignard reagent reacts with itself! <\/strong>Once formed, the Grignard\u00a0would react with the ketone from the starting material. This could then react with Mg to give a new Grignard, which would react with more ketone… and so on.\u00a0The result is a mess<\/strong>.<\/p>\n

    \"a<\/p>\n

    So how might we get around this?<\/p>\n

    <\/a>2. “Protecting Groups” Mask A Functional Group From Attack<\/h2>\n

    If we were able to find some way to “mask” the ketone in this case, possibly as some unreactive functional group that is completely inert to Grignard reagents, then we could then make the Grignard reagent without causing any problems of self-reactivity. \u00a0Then, once we’re done, we could then “unmask” the protecting or masking group, revealing our ketone again.<\/p>\n

    Like I said in this post (See article: Protecting Groups for Alcohols<\/a><\/em><\/span>), you use protecting groups a bit like how you use painter’s tape: when you’re painting a room, for instance, you’ll cover up your electrical outlet with painter’s tape, paint the room, and then remove the painter’s tape when you’re done.<\/p>\n

    \"how<\/p>\n

    <\/a>3. Acetals As A Protecting Group For Aldehydes And Ketones<\/strong><\/h2>\n

    As you might have suspected, there’s a decent solution for this. It turns out that different varieties of\u00a0ethers<\/strong> are great protecting groups because they’re unreactive towards strong bases and nucleophiles. Specifically in the case of ketones and aldehydes, a functional group called an\u00a0acetal<\/strong> (sometimes called “ketal”<\/b>) is great for the job. Acetals resemble ethers, except that we have a carbon attached to two O-R groups instead of one.<\/p>\n

    Acetals can be made from aldehydes and ketones by treating them with an alcohol and acid. [See post: Hydrates, Hemiacetals, and Acetals<\/a><\/em>] .\u00a0When the acetal protecting group isn’t needed anymore, the ketone or aldehyde can be restored by adding aqueous acid<\/strong> (H3<\/sub>O+<\/sup>).<\/p>\n

    \"one<\/p>\n

    OK, you might ask. So what? How does this work in real life?<\/p>\n

    <\/a>4. How To Use Protecting Groups In Grignard Reagent Synthesis: An Example<\/strong><\/h2>\n

    To answer this question, dear reader, let’s show a specific example.<\/p>\n

    The idea is that if <\/strong>\u00a0want to make a Grignard reagent on a molecule that contains an aldehyde or ketone, we need to protect that aldehyde or ketone beforehand\u00a0<\/strong>so that it doesn’t react with itself.<\/p>\n

    \"example<\/p>\n

    Let’s walk through the example above. Note that we have an aryl halide (a halogen attached to a benzene group) that we’d like to turn into a Grignard reagent. However, we also have a ketone. In order to make the Grignard and use it to form a bond with a different ketone, we’d need to protect the ketone on our first molecule.<\/p>\n