Sciencemadness Discussion Board - BzMgCl + MeCN, what did I get?

BzMgCl + MeCN, what did I get?

turd - 19-3-2006 at 08:13

I reacted benzyl magnesium chloride and acetonitrile (molar ratio 1:10) in THF for 24h at reflux (foolish in hindsight, but I thought that nitriles react slowly with Grignard reagents, so give 'em) and hydrolised with 10% HCl.

Extraction with EtOAc (foolish again, some of it decomposed) and distillation gave a yellow product which crystallised at room temperature. It smells rather nice actually, but different from phenylacetone. What please tell is it?

solo - 19-3-2006 at 10:01

Most likely a mixture of Benzyl chloride + Benzyl cyaninde + Methyl chloride + magnesium chloride........perhaps, ..........solo

turd - 20-3-2006 at 09:18

Quote:

Originally posted by solo
Most likely a mixture of Benzyl chloride + Benzyl cyaninde + Methyl chloride + magnesium chloride........perhaps, ..........solo

But none of those is a solid at room temperature (except MgCl2 of course, but that definitely did not distill at 130°C/20mbar). I will try to take a mp, but I fear the compound is not very clean.

But really, what *does* happen, when you overdo a Grignard reaction with a nitrile?

garage chemist - 20-3-2006 at 09:26

Your product is most likely 1,2-diphenylethane, the inevitable byproduct of every grignard with benzylmagnesiumchloride.

During preparation of the grignard, some of the benzylmagnesiumchloride forms diphenylethane, and if the reaction is allowed to become too hot, more of it will be formed.
Refluxing for a friggin 24 hours will completely convert your grignard into diphenylethane.

Diphenylethane formation is a big problem with BzMgX grignards, and often as much as 50% of the grignard is converted to this byproduct, even when the synthesis is done correctly, not allowed to get too hot, and immediately reacted with the desired reactant.

Perhaps make some tests to the identity of the product... diphenylethane should be completely nonpolar, insoluble in water, not affected by strong bases and acids (except H2SO4) etc...

turd - 20-3-2006 at 14:12

Thanks, garage chemist!

I hadn't realised that Wurtz-coupling would be an issue with Mg-compounds. In retrospect, I probably killed most of the BzMgCl during its creation - the reaction was violent!

Oh well, I'll recrystallise it and it will get a place on my shelf of useless oddities.

leu - 21-3-2006 at 17:44

Some organic halides are more likely to disproportionate than others, in the case of benzyl chloride this can happen if it or the magnesium isn't pure enough

Other factors that can promote the Wurtz reaction are if the solvent/halide ratio or the rate of halide addition isn't optimal

The classical preparation of benzylmagnesium chloride used diethyl ether as the solvent, not tetrahydrofuran

turd - 23-3-2006 at 15:04

A 1H-NMR of the yellow powder has a multiplet at >7ppm (weight 1.0), a sharp singlet at 2.9ppm (weight 0.41) and nothing else. Seems like it's pure. Is dibenzyl supposed to be yellow and to stink?

The BzCl, the Mg and the THF were clean, but apparently you're not supposed to form BzMgCl at reflux temperature of THF. Now back to phenyl-Grignards.

leu - 2-4-2006 at 14:10

The classical method of producing benzylmagnesium chloride in +90% yields has been posted on Wet Dreams; if you want to learn the proper method check it out :cool:

Sandmeyer - 2-4-2006 at 18:15

here's the HNMR spectra of Wurtz coupling product (90 MHz machine):

Sergei_Eisenstein - 3-4-2006 at 10:34

Strange you obtained only this compound. To make a Grignard, add magnesium in excess and filter it off once all precursor halide has reacted. Add CH3CN dropwise, maintaining a soft reflux. Do not add too rapidly, as Grignards can easily result in a runaway reaction.

Cloner - 3-4-2006 at 14:42

He made a grignard in THF as usual, then applied an enormous amount of acetonitrile to it, or do I misread the initial post?

Because the product that should be obtained then is what happens if the grignard attacks acetonitrile - this happens nearly instantaneous. This compound is an unstable intermediary which is usually broken down by acidic hydrolysis. Because the mixture was refluxed in THF, this intermediate compound might have had a party and reacted in unexpected manners.

The time of the reflux shold not affect wurtz coupling in this reaction, it's the temperature that could do it though (and the speed of adding reactant).

Sergei_Eisenstein - 4-4-2006 at 10:12

Quote:

Originally posted by ClonerThis compound is an unstable intermediary which is usually broken down by acidic hydrolysis.

The intermediary imine magnesium salt is not that unstable. As long as you keep the reaction setup free from water - which you should if you want your Grignard to give a good yield - the intermediary is stable. If desired, you can even filter it off. Next to solvolysis, the imine can be reduced to the amine as well.

Hemroid - 4-4-2006 at 14:51

Make the sodium bisulfite addition compound out of it and then decompose it with sodium carbonate.

[Edited on 4-4-2006 by Hemroid]

Hemroid - 4-4-2006 at 14:55

Benzyl magnesium chloride reacts immediately with acetonitrile (add one to the other slowly). Water decomposes the intermediate. Use a cheap organic solvent (ie. alcohol or toluene) to extract the organics from the magnesia. Boil down the solvent to get the organic compounds (P2P & impurities).

[Edited on 4-4-2006 by Hemroid]

Hemroid - 4-4-2006 at 14:59

You can make the sodium bisulfite addition compound using the extracted organics directly. Wash the crystals of the addition compound with organic solvent and then decompose with sodium carbonate in water. The P2P should float to the top. Extract the water with toluene or other immiscible solvent.

Cloner - 5-4-2006 at 08:32

Quote:

Originally posted by Sergei_Eisenstein

Quote:

Originally posted by ClonerThis compound is an unstable intermediary which is usually broken down by acidic hydrolysis.

I read this in another source as well, but in my hands, there is a fast formation of a 'glob' of some sort or another. Not at all a nice crystalline powder that can be washed and used for another reaction (reduction). There was definitely not that much water in the ether all the times, because the grignard reaction proceeded well. Also, there should be enough MgBr2 from initiation by ethylene dibromide, to catch the odd water molecule.

Sergei_Eisenstein - 5-4-2006 at 10:27

Quote:

I have not performed the exact reaction, but I did react benzylmagnesium chloride with propionitrile. If I remember the details correctly, the solution turned grey at first and clogged up completely as the reaction proceeded. This was not really a crystalline powder, but more an off-white solid cake. I took a bit of the cake out of the mixture and vacuum filtered it, washing it with some ether. It did not discolorize on standing over an hour or so. I readded it to the mixture and added dilute HCl to obtain the ketone. I hoped it would have some sort of a pleasent smell, but it disappointed me a bit.

About the first post: I think it's a problem with the amount of Mg added. Half formed the Grignard, the other half reacted with the Grignard. Not enough Mg, or maybe it took way too long to add all Mg.

trilobite - 17-4-2006 at 17:25

The problem with the reaction is that acetonitrile has an acidic alpha-hydrogen. The Grignard can abstract this proton, giving a hydrocarbon (toluene with benzylmagnesium chloride) and a magnesio derivative of acetonitrile, ClMg-CH2-CN which may add to another nitrile function to give oligomeric condensation products (beta-ketonitriles on hydrolysis). This is discussed in J. Org. Chem 15, 359-66 (1950). Phenylacetonitrile and acetonitrile seem to be both quite problematic, the former being relatively acidic and the latter sterically unhindered. This is why propionitrile works better.

If the solvent system is changed to a less polar one, the Grignard reagent will have less ionic nature and the proton abstraction will be slower. Here is an abstract:

Effect of benzene in the Grignard reaction of nitriles.
Canonne, Persephone; Foscolos, George B.; Lemay, Gilles.
Tetrahedron Letters, 21(2), 155-8 (1980).

Abstract
The use of C6H6 contg. 1 equiv. of Et2O as solvent for Grignard reactions of nitriles at room temp., led to increased yields of the corresponding ketones compared to reactions using Et2O as solvent, and also to an elimination of the undesirable side reactions. E.g., PhCH2MgCl reacted with MeCN in Et2O to give 29% MeCOCH2Ph (I), whereas in C6H6 I was obtained (48%).

On Rhodium archives there are methods describing the reactions of both acetonitrile + PhCH2MgCl and phenylacetonitrile with MeMgI. The methods using acetonitrile give no yields of purified product, only that of crude materials, so I guess the yields are quite much lower in reality. Furthermore it might be that the phenylacetonitrile method with one pot reduction with NaBH4 to the amine doesn't give as good yields as advertised, but who knows.