Sciencemadness Discussion Board

Mechanism of benzyl cyanide synthesis ?

devongrrl - 3-12-2011 at 03:52


Could some aid me with a mechanistic overview of the Benzyl CN synth please ?

I searched and found the actual synth itself in Org Syn but not the mechanism.

Secondly, I note the reaction can be run using NaCN or KCN but presumably not with MeCN ?

kavu - 3-12-2011 at 04:08

It's an SN1 reaction. Chloride anion leaves forming a benzylic cation cation, which is stabilized by the delocalization of charge over the benzene ring. Cyanide ion (CN⁻ ) then attacks the anionic carbon and forms the product. This is not possible with organic nitriles as the nitrile carbon sp-orbital needed for the attack is used up by the σ-bond with carbon chain.

[Edited on 3-12-2011 by kavu]

DJF90 - 3-12-2011 at 05:23

It ccould also proceed via an Sn2 mechanism, and likely occurs via both pathways simultaneously.

Nicodem - 5-12-2011 at 13:23

Nucleophilic substitutions on benzyl chloride with such basic nucleophiles proceed via SN2. If it would proceed via SN1, or just partially SN1, then benzyl alcohol and benzyl ethyl ether would form under the conditions used in the Org. Synth. procedure. The high yield of phenylacetonitrile and no reports of side products makes the SN1 pathway appear insignificant. In principle, benzyl halides with strongly carbocation stabilizing ortho or para substituents, such as the methoxy groups, can undergo SN1 substitutions in neutral media. This might explain the use of acetone in the preparation of p-methoxyphenylacetonitrile from p-methoxybenzyl chloride, but I'm sure there are studies published on this topic which could be found by those interested.

Benzyl halides and alcohols do however relatively readily undergo SN1 substitutions in acidic media. One such example was recently reported by our member kmno4.

Otherwise, this question was already addressed in an old thread and the mechanism of this specific reaction was depicted there.

MeCN is acetonitrile and as such it can not be a source of cyanide ions.

PS: Please open referenceless and/or beginner's thread in the Beginnings section of the forum where this is being moved.

turd - 5-12-2011 at 15:03

What is the synthesis of benzyl cyanide anyway? It could also be made by oxidation of beta-phenylethylamine, for example with TCCA, isn't it?

Dr.Arz - 18-10-2014 at 18:13

Anyone have any confirmed data on toxicity of benzyl cyanide? Different sources cite that LD50 oral and dermal rat and rabbit is 270mg/kg, while guinea pig it is only 10mg/kg. Former would mean it is not of concern, but latter lists it at the same level as sodium cyanide which means its liquid toxin.

Chemosynthesis - 18-10-2014 at 18:25

Quote: Originally posted by Dr.Arz  
Anyone have any confirmed data on toxicity of benzyl cyanide? Different sources cite that LD50 oral and dermal rat and rabbit is 270mg/kg, while guinea pig it is only 10mg/kg. Former would mean it is not of concern, but latter lists it at the same level as sodium cyanide which means its liquid toxin.
Health and Human Services has no data for human LD50, which is not at all uncommon in toxicology.

You're left to draw your own extrapolatory conclusions. However, be aware that sublethal doses in rats did cause nephrotoxicity and neither oral nor IV cyanide treatments (cobalt edetate) were therapeutic. Testing with white mice showed the ability to penetrate skin, by the way. I suggest care in handling.