Sciencemadness Discussion Board

benzyl alcohol to benzyl cyanide

preetikaagrawal - 19-4-2008 at 23:30

why can we convert benzyl alcohol directly to benzyl cyanide using KCN why should we convert it first to benzyl bromide with HBr and then to benzyl cyanide with KCN?????????

Sauron - 20-4-2008 at 00:10

Read Vogel on preparation of nitriles.

Or Katritzski, Comprehensive Organic Finctional Group Transformations

As far as I am aware, you can't directly convert a benzylic -OH to -CN.

Or any other hydroxyl for that matter.

Klute - 20-4-2008 at 07:54

the -OH is not a good leaving group under SN2 conditions. -OH2+ is a better leaving group, but that would cause the CN- to be under the form of the volatil HCN, which isn't a nucleophile.
Making benzyl bromide or chloride is very easy, simply stir with conc acid (HBR or HCl).
I would advise you to read much more before planning on using cyanides....

Sauron - 20-4-2008 at 09:25

Benzyl chloride and benzyl bromide are highly irritating and lachrymatory and Sartori lists them as "war gases" although they are not considered such under CWC.

Their handling and use really demands a good fume hood and protective gear.

Benzyl cyanide (phenylacetonitrile) is commercially available. In my locale it is something I can buy whereas the bromide and chloride are restricted by the M.O.D. So I just buy it rather than having to do two steps from the alcohol.

Nicodem - 21-4-2008 at 04:04

A scheme of the above explanations for pedagogical purposes (yes I was indeed quite bored to do this :P).

For further reading see:

SN2 substitutions: http://en.wikipedia.org/wiki/SN2_reaction

SN1 reaction of carbocations with HCN and nitriles (Ritter reaction):
http://www.organic-chemistry.org/namedreactions/ritter-react...

benzyl.gif - 32kB

PainKilla - 21-4-2008 at 18:13

I haven't tried this but it looks like it would work rather well:

[Edited on 21-4-2008 by PainKilla]

Attachment: US3496211 - Preperation of Cyanoalkylated Phenols by the Reaction of a Metal Cyanide and Hydroxybenzyl phenols.pdf (215kB)
This file has been downloaded 954 times

chemrox - 21-4-2008 at 21:59

nice table there nicodemus!

Nicodem - 22-4-2008 at 02:33

PainKilla, I think that patent might works as advertised. Such reactions involving 1,6-elimination of H2O followed by a 1,6-conjugative addition are not only theoretically possible but there are other examples known as well. But like with all patents, you always have to try it out to see for your self how well, if at all, it actually works.

In relation to the original question, the activation of benzyl alcohols and SN2 with cyanide can be done using a one-pot procedure as well, though economically it is only rational to do so with substrates more expensive than plain unsubstituted benzyl alcohol. See:
A simple one-pot procedure for the direct conversion of alcohols into alkyl nitriles using TsIm (attached)
Mohammad Navid Soltani Rada, Ali Khalafi-Nezhadb, Somayeh Behrouzb and Mohammad Ali Faghihi
Tetrahedron Letters, 48 (2007) 6779-6784.
DOI: 10.1016/j.tetlet.2007.07.091

Attachment: one-pot procedure for the direct conversion of alcohols into alkyl nitriles.pdf (162kB)
This file has been downloaded 4203 times

Nicodem - 23-4-2008 at 11:54

This is quite off topic, though still somewhat connected to the patent PainKilla provided above.
I got interested in these nucleophilic 1,6-conjugative additions on p-quinomethanes (also called p-quinone methides in older literature) which seem to form relatively easily from p-hydroxybenzyl alcohols under the influence of either bases, acids and/or heat trough the formal elimination of water. The driving force for the 1,6- versus 1,2- or 1,4-addition is obviously the rearomatization of these reactive species. Since I went searching for more examples of this reaction, I thought to post a compilation of some references. Some of these reactions are well in the possibilities of home chemists (especially since 4-hydroxy-3-methoxybenzyl alcohol can be prepared from vanillin) and can lead to complex and fascinating products even by using such a OTC nucleophile as ascorbic acid (see J. Org. Chem., 53 (1988) 1535-1540).
Bellow is some examples from the literature using nucleophiles other than cyanide:

quinomethanes.gif - 22kB

PainKilla - 24-4-2008 at 07:21

Thanks for the overview Nicodem!

That looks like a very useful reaction too, nitriles aside. I wonder if non-phenolic substrates have been studied (anilines, halogens), as it seems that the mechanism might be able to be carried over to those substrates as well.

In any event, as far as the original post is concerned, I don't see what the problem with making the benzyl halide is. The conversion is near quantitative and very easy to do, and replacement with cyanide even easier.

Nicodem - 26-4-2008 at 14:27

It does work on ortho-hydroxybenzyl alcohols as well. Of course, these form the ortho-quinomethanes instead. Besides the similar reactivity toward nucleophiles, these have an additional feature of being very good dienes for the hetero-Diels-Alder reaction with dienophiles (see: Chem. Commun. (1999) 691–692).
Otherwise, I did not find any examples of corresponding nitrogen species forming from 4-aminobenzyl alcohols. Though I did find one example of a para-quinomethane formed from 3,5-di-t-butyl-4-hydroxybenzyl chloride by the action of triethylamine (I did not put much more than a couple of minutes of effort into searching so I must have missed something). Otherwise there are also plenty of other methods to make quinomethanes in situ, but none is so simple as the dehydration of p- and o-hydroxybenzyl alcohols.

kmno4 - 29-4-2008 at 03:18

Quote:
Originally posted by preetikaagrawal
why can we convert benzyl alcohol directly to benzyl cyanide.... (...)

I thought about this a long time ago and thought out nothing :(
Funny article:
A simple one-pot procedure for the direct conversion of alcohols into alkyl nitriles using TsIm.
One-pot yes, but is it direc ? I can take benzyl alcohol (and few other ones) and add HCl(aq), wait an hour or two, add excess of NaCN and I can write article: Very simple one-pot and direct conversion of alcohols into nitriles
This (most propably) multistep reaction is not "activation of benzyl alcohols and SN2 with cyanide" in my opinion.
BTW. Benzylation of compounds with activated H atoms with benzyl alcohol is known for a long time. For example from b.alcohol and aniline is easy to prepare C6H5CH2-NH-C6H5 (with aid of KOH, as far I remember)

Nicodem - 29-4-2008 at 11:28

Quote:
Originally posted by kmno4
Funny article:
A simple one-pot procedure for the direct conversion of alcohols into alkyl nitriles using TsIm.
One-pot yes, but is it direc ? I can take benzyl alcohol (and few other ones) and add HCl(aq), wait an hour or two, add excess of NaCN and I can write article: Very simple one-pot and direct conversion of alcohols into nitriles
This (most propably) multistep reaction is not "activation of benzyl alcohols and SN2 with cyanide" in my opinion.

If you think you can make BnOH>BnCl>BnCN a one-pot method then try, but the BnOH>BnCl requires a large excess of HCl so I really don’t think you can do much with it. On the other hand N-tosyl-imidazole cleanly O-tosylates alcohols and the so formed imidazole does not interfere with the SN2 with cyanide. It is a nice method that works on not only benzyl alcohols but aliphatic alcohols as well. The drawback is the terrible price of N-tosyl-imidazole or the work involved in its preparation.
Quote:
BTW. Benzylation of compounds with activated H atoms with benzyl alcohol is known for a long time. For example from b.alcohol and aniline is easy to prepare C6H5CH2-NH-C6H5 (with aid of KOH, as far I remember)

I guess you mean this nice method:

Reduction and Benzylation by Means of Benzyl Alcohol. II. N-Benzylation. The Preparation of Secondary Aromatic Benzylamines (attached)
Yaïr Sprinzak
J. Am. Chem. Soc., 78 (1956) 3207–3208. DOI: 10.1021/ja01594a064

It is a very interesting reaction, particularly in its mechanistic aspect.
Using nickel or Ru/Ir/etc catalysts for the so called “disproportionative condensation” methods for preparing amines from alcohols works well on benzaldehyde. In this type of reaction the dehydrogenation of the alcohol serves as a source of hydrogen for the reduction of the imine formed from the ketone itself formed by alcohol dehydrogenation (funny cycle, isn’t it?). Two examples using metallic nickel:
Journal of the American Chemical Society, 76 (1954) 6174-6179.
Synthetic Communications, 26 (1996) 161-164.

Attachment: Reduction and Benzylation by Means of Benzyl Alcohol II.pdf (265kB)
This file has been downloaded 958 times

kmno4 - 9-5-2008 at 07:23

Quote:
Originally posted by Nicodem
If you think you can make BnOH>BnCl>BnCN a one-pot method then try, but the BnOH>BnCl requires a large excess of HCl so I really don’t think you can do much with it. On the other hand N-tosyl-imidazole cleanly O-tosylates alcohols and the so formed imidazole does not interfere with the SN2 with cyanide. It is a nice method that works on not only benzyl alcohols but aliphatic alcohols as well. The drawback is the terrible price of N-tosyl-imidazole or the work involved in

An example with with benzyl aclohol/ HCl(aq) is not so good, from practical point of view, I know ;) But from elusive reference* reaction: 1 ØOH / 2 ZnCl2 / 2 HCl gives (without heating) quantitative yield of benzyl chloride. There is no problem with adding to this mixture (after conversion alcohol into chloride) solution of NaCN (with excess) in ethanol+water. It could be one pot.
Authors of "direct" conversion alcoholes into nitriles state that reaction goes via alkyl tosylates, so not directly from alcohols.
If you think you can make BnOH>BnCl>BnCN a one-pot method.... I feel that it is possible. I used to try this, but without special successes. Now I have some new ideas ;).
I have larger amounts each of these substances, I want only to see if this conversion is possible. I do not pray to/for benzyl cyanide, as some others surely do :P.

*http://www.orgsyn.org/orgsyn/orgsyn/prepContent.asp?prep=cv1p0144
reference no. 3 ( because of some stupid reasons (unknown to me) some user does not want to share this article)

Nicodem - 9-5-2008 at 11:02

Well, I guess you are right about the phrase "direct conversion" being somewhat inappropriate, but one-pot methods are often called direct preparations. Even if a one-pot synthesis involves three or four synthetic steps it is still considered a direct preparation (“conversion” is more commonly used for reaction steps and is thus also somewhat inappropriate). It is just a matter of ambivalent terminology, but in this case direct and conversion pertains to the preparation and not reactions.

You could try your one-pot with 1.1 eq. conc. HCl + 1 eq. ZnCl2 in methanol at room temperature, then add 1.5 eq. anhydrous K2CO3 to quench all the ZnCl2 and the residual HCl, followed by 1.5 eq. KCN and reflux for a couple of hours. That would make it a one-pot method of BnOH to BnCN. However, you would have to monitor with TLC, especially the first reaction step. The SN2 on benzyl chlorides in methanol or ethanol with KCN is well described so this step is likely to work.

EDIT: Never mind, I just realized the cyanide anions complex with zinc ions to form tetracyanozincates.

[Edited on 10/5/2008 by Nicodem]