{"id":9301,"date":"2015-11-13T17:34:06","date_gmt":"2015-11-13T22:34:06","guid":{"rendered":"https:\/\/www.masterorganicchemistry.com\/?p=9301"},"modified":"2026-05-07T09:37:34","modified_gmt":"2026-05-07T14:37:34","slug":"organometallics-are-strong-bases","status":"publish","type":"post","link":"https:\/\/www.masterorganicchemistry.com\/2015\/11\/13\/organometallics-are-strong-bases\/","title":{"rendered":"Organometallics Are Strong Bases"},"content":{"rendered":"

Reactions of Grignard Reagents With Water, Carboxylic Acids, And Other Mildly Acidic Species<\/strong><\/p>\n

Last post we talked about how to make certain organometallics<\/a>, specifically Grignard and organolithium reagents. One thing we saw is that they tend to be strong bases, as they are the conjugate bases of alkynes (pKa<\/sub> \u2248 25), alkenes (pKa<\/sub> \u2248 42) and alkanes (pKa<\/sub> \u2248 50)<\/p>\n

“Alright”, you might say. Grignards and organolithiums are strong bases. “So what? What does that mean? ”<\/p>\n

It’s a big deal, actually. The purpose of today’s post is to show some important consequences of this fact.<\/p>\n

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

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

    \n
  1. Organometallics Will React With\u00a0 Water, Alcohols, Carboxylic Acids And Other Mild\u00a0 Acids<\/a><\/li>\n
  2. A Useful Application:\u00a0 Incorporating Deuterium (D)<\/a><\/li>\n
  3. Why trying to make a Grignard reagent of a molecule that also has an acidic hydrogen (e.g. OH, CO2<\/sub>H) is doomed to failure<\/a><\/li>\n
  4. Notes (Using Protecting Groups)<\/a><\/li>\n
  5. Quiz Yourself!<\/a><\/li>\n<\/ol>\n
    \n

    <\/a>1. Organometallics Are Strong Bases, And Will React With Acids (Even Weak Ones)<\/strong><\/h2>\n

    Since Grignard and organolithium reagents are among the strongest bases known, not only will they react with conventional “strong acids” such as hydrogen halides (e.g. HCl), they will readily undergo acid-base reactions with species we often don’t consider to be very acidic, such as water (pKa<\/sub> 14), alcohols (pKa<\/sub> 16-18), terminal alkynes (pKa<\/sub> 25) or even amines (pKa<\/sub> 35-38).<\/p>\n

    After all, if you’ve had to make Grignard reagents in the lab – and many of you will – one of the first things you’ll be told is the importance of keeping your solvents and glassware bone-dry<\/strong>. If traces of water\u00a0are present in your solvent,\u00a0your Grignard\u00a0will react with\u00a0it in a simple acid-base reaction, forming the conjugate acid of the Grignard (an alkane or alkene\/arene) and a (much less basic) hydroxide ion.<\/p>\n

    For this reason, for the synthesis of Grignard reagents we always choose solvents without acidic protons that can be easily dried. Ethereal solvents such as diethyl ether and tetrahydrofuran (THF) are perfect choices.<\/p>\n

    \"organometallic<\/p>\n

    Think of\u00a0these reagents\u00a0as lit\u00a0candles\u00a0– potentially very powerful, but also vulnerable to being extinguished. [As anyone who has worked with t-butyllithium can attest, the “candle”analogy is perhaps a little\u00a0too applicable – dispensing this liquid by syringe is often\u00a0accompanied by a small tip of flame at the syringe tip where drops of liquid spontaneously combust with oxygen in the air.]<\/em><\/span><\/p>\n

    <\/a>2. A Useful Application – Incorporating Deuterium<\/h2>\n

    On occasion, this “annoying” proclivity of weak acids to interfere with reactions of Grignards and organolithiums can be used to our advantage. For example, substituting D2<\/sub>O for water provides us with an excellent method for incorporating deuterium<\/strong> labels into molecules:<\/p>\n

    \"grignard<\/p>\n

    <\/a>3. Complications In Forming Grignard Reagents<\/strong><\/h2>\n

    Knowing that organometallics such as Grignard and organolithium reagents are strong bases, can you see a reason why formation of the organometallic\u00a0reagents below wouldn’t work?<\/p>\n

    \"grignard<\/p>\n

    Note that each of these molecules has an acidic proton! So as soon as any Grignard forms, it would immediately be neutralized by the acidic functional group to give us the conjugate acid of our organometallic (which is useless to us) and the conjugate base of whatever the acidic functional group is. [And don’t forget – acid base reactions are fast<\/a>, <\/strong>relative to other types of reactions.\u00a0\u00a0There’s no chance you’d get the “desired” reaction in before the acid-base reaction occurred]<\/em><\/span><\/p>\n

    By the way, this issue makes for some very common “trick questions” on exams –\u00a0so keep an eye out.<\/p>\n

    Using the term “useless” two paragraphs up begs the question – “what are Grignard reagents used for, anyway?”<\/p>\n

    We cover that in the next post<\/strong><\/a>. Stay tuned.<\/p>\n

    \n

    <\/a>Notes<\/h2>\n

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