Organometallics Are Strong Bases

by James

in Organic Chemistry 1, Organic Chemistry 2

Last post we talked about how to make certain organometallics, specifically Grignard and organolithium reagents. One thing we saw is that it’s useful to think of them as “carbanions”, that is, carbons bearing a negative charge. We’ve also seen that carbanions tend to be strong bases, as they are the conjugate bases of alkynes (pKa ≈ 25), alkenes (pKa ≈ 45) and alkanes (pKa ≈ 50)

“Alright”, you might say. Grignards and organolithiums are strong bases. “So what? What does that mean? ”

The purpose of today’s post is to show some important consequences of this fact.

Organometallics Are Strong Bases, And Will React With Acids (Even Weak Ones)

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

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. If traces of water are present in your solvent, your Grignard will react with itin a simple acid-base reaction, forming the conjugate acid of the Grignard (an alkane or alkene/arene) and a (much less basic) hydroxide ion.

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.

1-organometbase

Think of these reagents as lit candles – 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 too applicable – dispensing this liquid by syringe is often accompanied by a small tip of flame at the syringe tip where drops of liquid spontaneously combust with oxygen in the air.]

A Useful Application – Incorporating Deuterium

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 D2O for water provides us with an excellent method for incorporating deuterium labels into molecules:

2-organometbase

Complications In Forming Grignard Reagents

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

3-organometbase

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, relative to other types of reactions.  There’s no chance you’d get the “desired” reaction in before the acid-base reaction occurred]

By the way, this issue makes for some very common “trick questions” on exams – so keep an eye out.

Using the term “useless” two paragraphs up begs the question – “what are Grignard reagents used for, anyway?”

We cover that in the next post. Stay tuned.

[The following topic on protecting groups might not be covered for you until later in your course. I’m including it below for completeness, although for many students it can be profitably skipped for now.]


 

[Extra] Masking Acidic Functional Groups Using “Protecting Groups”

As you might have suspected, there is a way around the problem of acidic functional groups in formation of Grignard reagents. The solution is quite simple in concept.

As I said in my previous post on protecting groups, they’re a bit like the chemical equivalent of “painter’s tape”.

  1. We “mask” the acidic functional group by converting it into a functional group that won’t react with our Grignard.
  2. We form the Grignard, and then employ it for our chosen purpose.
  3. When that reaction is complete, we remove the functional group, unmasking that “acidic” functional group.

The key features of the functional group for these purposes is that it be unreactive with Grignard reagents (in this case) and that there exist methods to install and remove the protecting group without affecting other parts of the molecule. (We often throw in the math term “orthogonal” to refer to this latter property).

Let’s look at a specific example.

I’m going to leave the actual “protecting group” vague for these purposes as “PG” – if you need more specific details, see my post on protecting groups for alcohols. In general, certain types of ethers are useful – silyl ethers in particular, since they’re easily installed (trimethylsilylchloride [TMSCl] being one example) and removed (fluoride ion will selectively cleave silyl ethers).

4-organometbase

The concept of “protecting groups” is not confined just to alcohols, of course – there are also ways to mask carboxylic acids, aldehydes, ketones, and many other functional groups that have a tendency to “get in the way” of Grignard reagents.

In the next post, we’ll talk about some common reactions of Grignards and organolithium reagents. Wait…. I think we’ve already done that, in my Reagent Friday on Grignards. Well, visit that Reagent Friday post first, and then follow the link to our next post on organocuprate reagents (Gilman reagents).

Next Post: Reactions of Grignard Reagents

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