{"id":9286,"date":"2015-11-09T16:35:26","date_gmt":"2015-11-09T21:35:26","guid":{"rendered":"https:\/\/www.masterorganicchemistry.com\/?p=9286"},"modified":"2026-01-22T09:35:57","modified_gmt":"2026-01-22T15:35:57","slug":"synthesis-of-grignard-and-organolithium-reagents","status":"publish","type":"post","link":"https:\/\/www.masterorganicchemistry.com\/2015\/11\/09\/synthesis-of-grignard-and-organolithium-reagents\/","title":{"rendered":"Formation of Grignard and Organolithium Reagents"},"content":{"rendered":"

Formation or Grignard Reagents and Organolithium Reagents From Alkyl and Alkenyl Halides<\/strong><\/p>\n

In the last post<\/a> we introduced the concept of organometallic compounds – molecules where carbon is bound to a less electronegative atom such as Li, Mg, Cu, and many other metals. We said that carbon in these molecules tends to be electron-rich and thus have nucleophilic<\/em> character, in contrast to functional groups such as alkyl halides, aldehydes, ketones, and epoxides where carbon has electrophilic<\/em> character. If you need a refresher on what I meant by nucleophilic<\/strong> and electrophilic<\/strong>, read that post first.<\/a><\/p>\n

In this post we’ll talk about how certain types of organometallic compounds are made – specifically organolithium and Grignard reagents.<\/strong><\/p>\n

Quick summary:<\/p>\n

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

Let’s start with organolithium reagents because they’re the simplest.<\/p>\n

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

    \n
  1. Organolithium Reagents As Carbanions (The Conjugate Bases Of R-H)<\/a><\/li>\n
  2. Making Carbanions Through Reduction, Not Deprotonation<\/a><\/li>\n
  3. Formation of Organolithium Reagents From Alkyl Halides<\/a><\/li>\n
  4. Formation of Grignard Reagents:\u00a0 The Mechanism<\/a><\/li>\n
  5. Notes<\/a><\/li>\n
  6. Quiz Yourself!<\/a><\/li>\n
  7. (Advanced) References and Further Reading<\/a><\/li>\n<\/ol>\n
    \n

    <\/a>1. Organolithium Reagents As Carbanions<\/h2>\n

    If you look closely, you can approximate the structure of an organolithium reagent (R-Li) as “R(\u2013)” , with lithium as the positive counter-ion: in other words, a carbon bearing a negative charge\u00a0<\/em>(we call these species “carbanions”). If you think back to earlier lessons on acids and bases, this structure might look familiar – it’s the conjugate base<\/strong> of a species R-H.<\/p>\n

    Using butane to stand in for “R-H” here, we get:<\/p>\n

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

    Since conjugate bases are made through deprotonation, we might naively think that we could make organolithium species by taking an organic molecule and just adding a super-strong base to rip off the proton.<\/p>\n

    If you’ve covered alkynes, you’ve seen that that process actually works pretty well in the case of terminal alkynes<\/a>. They are quite acidic species, having a pKa<\/sub> of 25 or so. Their unusually high acidity is due to the considerable s-character on the carbon (meaning that the lone pair is held closely to the nucleus).<\/p>\n

    Trouble is, as we move towards alkenes and alkanes, the direct deprotonation approach doesn’t work so well. That’s because… well, it’s hard to find any species more basic than a deprotonated alkane!<\/strong> Just as the only thing sharp enough to cut a diamond is another diamond, about the only thing basic enough to deprotonate an alkane is… another deprotonated alkane.<\/p>\n

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

    This isn’t a practical approach to make organolithiums for several reasons – primarily, the fact that there are often many C-H bonds and it’s hard to selectively remove just one. [For instance, if you tried to make 1-pentyllithium by deprotonating pentane, you could potentially end up with multiple different isomers].<\/em><\/span><\/p>\n

    Thankfully, another approach has been devised.<\/p>\n

    <\/a>2. Making Anions Through Reduction, Not Deprotonation<\/b><\/h2>\n

    If you look at the reaction below, and count the electrons carefully, you might note that the product has\u00a0two more electrons<\/strong> than the starting material. In other words, particularly if you remember the OIL RIG<\/a> mnemonic,\u00a0reduction<\/strong> has occurred.<\/p>\n

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

    This means that if we were to add some species which was particularly likely to give up its electrons,<\/strong> we might thus be able to effect this transformation.<\/p>\n

    Can you think of any members of the periodic table which hold onto their electrons particularly loosely?<\/strong> If you said “the far left part of the periodic table” (particularly the alkali and alkaline earths), ding ding ding! you would be correct.<\/p>\n

    Lithium<\/strong>, in short, would be a great choice as a reductant for this reaction. [We’ll get to the other metals in a minute].<\/p>\n

    What might be a good choice for\u00a0X? One factor\u00a0which would make this reaction easier is if X(\u2013)\u00a0<\/span><\/span>was a fairly stable species – a good leaving group<\/a>, in other words. Good candidates for X are halides such as Cl, Br, and I. A bad candidate would be H(\u2013)\u00a0 or some other strongly basic version of R(\u2013) , since we’d be generating another unstable anionic species.<\/p>\n

    Now let’s get to specifics.<\/p>\n

    <\/a>3. Making Organolithium Reagents From Alkyl Halides<\/strong><\/h2>\n

    Lithium, having a very low ionization energy (i.e. it loses its electron easily) is a powerful reducing agent. \u00a0Since lithium only has a single valence electron, however, we must add two equivalents<\/strong> if we are to complete the reduction reaction.<\/p>\n

    To make organolithium reagents, we start with alkyl halides, and add powdered lithium metal (Li or sometimes written as Li0 <\/sup>to distinguish it from the ion Li(+)\u00a0).<\/p>\n

    Occasionally the solvent for this reaction is written below the arrow. A common solvent is pentane. Some instructors like to include it. Some don’t. Regardless of whether it’s written there or not, it doesn’t participate in the reaction.<\/p>\n

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

    This reaction works for alkyl chlorides, bromides, and iodides, as well as alkenyl halides (fluorides excepted).<\/p>\n

    If you recall that alkyl halides can be made from halogenation of alkanes, this method thus gives us a 2-step method for formation of highly basic alkyl lithium species from alkanes.<\/p>\n

    For a pop-up view of the mechanism hover here\u00a0 <\/a> or click on the link<\/a>.<\/p>\n

    We’ll cover the many useful applications of organolithium reagents in a future blog post.<\/p>\n

    I’m going to skip\u00a0organoberyllium\u00a0reagents here (beryllium is highly toxic, and rarely sees use)\u00a0\u00a0and move straight across from sodium over to magnesium, which comprises a second very important family of organometallic reagents.<\/p>\n

    The process for making Grignard reagents is very similar to making organolithium reagents: start with an appropriate alkyl halide and add magnesium<\/strong>. Since magnesium has two valence electrons, only one equivalent of Mg is required to balance the reaction. Here’s two examples, showing formation of alkyl and alkenyl Grignard reagents.<\/p>\n

    Note that Grignards can be made from alkyl or alkenyl chlorides, bromides, and iodides – but not fluorides.<\/p>\n

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

    What, you might ask, are Et2<\/sub>O and THF? These are solvents, which are often written in the reaction scheme, but don’t actually participate in the reaction itself. \u00a0Et2<\/sub>O (diethyl ether, or, sometimes, “ether”) and THF (tetrahydrofuran) are popular choices. \u00a0If you’re an introductory student, you probably don’t want to know the deeper reasons why, nor do you need to, so don’t click this link to find out.<\/a><\/p>\n

    In\u00a0contrast with most of the reagents and reactions we talk about at MOC, you’ll likely have personal experience doing this reaction!<\/p>\n

    Sitting\u00a0around for a few minutes staring at\u00a0your flask containing Mg, ether, and organohalide do absolutely nothing is a\u00a0rite of passage for every student of organic chemistry.<\/p>\n

    One key contributor to the “finicky” nature of forming Grignard reagents is that the reaction<\/strong> occurs on the surface of the magnesium metal<\/strong>. For this reason the reaction is highly surface area dependent. Breaking the Mg up into very small chunks will accelerate the reaction. Furthermore, Mg that has been sitting out in the open for awhile often has a surface coating of magnesium oxide (MgO) which is unreactive with alkyl halides. Breaking up the surface helps to expose fresh, unoxidized Mg to the reactants. A pinch of iodine (I2<\/sub>) or 1,2-dibromoethane can also help to kick-start things.<\/p>\n

    <\/a>4. Formation of Grignard\u00a0 Reagents: The Mechanism<\/h2>\n

    What’s the mechanism of Grignard formation? Usually not covered – it involves free radicals – but if you’re curious, hover here for a pop-up view or <\/a> click on this link<\/a>.<\/p>\n

    From a practical perspective, one key thing to make sure of when preparing organolithium or Grignard reagents is that the solvent and glassware are completely dry.<\/strong> Water (pKa<\/sub> 14) is death to Grignard and organolithium reagents, which as we said above, act as the equivalent of highly basic alkyl and alkenyl anions.<\/p>\n

    In the next post, we’ll talk about this and also some other complications of making Grignard reagents.<\/p>\n

    Next post: Organometallics Are Strong Bases<\/a><\/strong><\/p>\n

    \n

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

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