Sciencemadness Discussion Board - Alkyl chlorides, Bromides and Iodides

Alkyl chlorides, Bromides and Iodides

Sauron - 6-3-2008 at 20:14

A member asked me for a very efficient prep for alkyl chlorides from alcohols.

This is the most efficient that I know. With modifications it can be used to prepare bromides and iodides.

I have posted it previously in a zip folder but that file is now corrupt so I have no compunction about reposting.

Astute readuers will note that+ the TCT-DMF adduct fails with NaI to give the alkyl iodides, but, that conversion using TCT and NaI is described in

Chem. Ind., 1416 (1971).

a paper I do not yet have at hand.

[Edited on 7-3-2008 by Sauron]

Attachment: TCTDMF.pdf (54kB)
This file has been downloaded 824 times

chemrox - 12-3-2008 at 22:46

Thank you Sauron- I was looking for this in my files too. I have an alcohol I wish to make into a chloride and I'm wondering how this compares with HCl/ZnCl in terms of yield and cost? I suppose the good of the order motive would lead to trying both approaches and reporting back.

PHILOU Zrealone - 13-3-2008 at 04:42

Quote:

Originally posted by chemrox
Thank you Sauron- I was looking for this in my files too. I have an alcohol I wish to make into a chloride and I'm wondering how this compares with HCl/ZnCl in terms of yield and cost? I suppose the good of the order motive would lead to trying both approaches and reporting back.

I had the same question in mind, it would be good to compare...HX and Lewis acids vs the TCT method; although TCT method is interesting solution.

HX and Lewis acid:
-Cheap starting reactants, easy especially in the case of sec and tert alcohols.
-Easy recovery of the halogenated compound (I don't know if for the TCT method DMF and hydroxy-DCT are easily separable from the target halide, especially in the case of bifunctional compounds like the ones they mention in the attachement (amino alcohols, diols.) or carboxylic alcohols (glycolic alcohol or tartric acid for example).

On a side note I find it frustrating :mad:

that only one halide equivalent is apparently used while TCT contains 3 of them

another method

chemrox - 14-3-2008 at 18:19

Here's another mild conditions method that was cited by the authors of the paper Sauron gave us here. The yields range from a terrible 15% to a wow 100%. The TCT/DMF process is much more comsistent. I cite this for completeness and in case someone wants to use it for whatever reason.

Attachment: ionic liqs OH-X.pdf (24kB)
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-jeffB - 14-3-2008 at 18:40

Quote:

Originally posted by chemrox
Here's another mild conditions method that was cited by the authors of the paper Sauron gave us here. The yields range from a terrible 15% to a wow 100%. The TCT/DMF process is much more comsistent. I cite this for completeness and in case someone wants to use it for whatever reason.

Hmm! I've been wanting to tinker with ionic liquids, but they tend to be QUITE expensive. However, there are a bunch of "deep eutectic" mixes based on choline chloride that act as ionic liquids -- including a 2:1 molar mix with urea. It would be interesting to see whether any of these reactions could be done in this extremely cheap and green solvent system.

vulture - 15-3-2008 at 02:58

A modified Appel synthesis with PPh3 and NBS in DCM @ 0C is also a clean method with high yields. Only drawback is the PPh3=O you need to get rid of, but that can be done by vacuum distillation if your product is volatile.

Diagonal reading of that paper reveals that optically active alcohols are inverted. The modified appel synthesis retains stereochemistry (through double inversion).

[Edited on 15-3-2008 by vulture]

Nicodem - 15-3-2008 at 05:59

If distillation is not an option, there is also another efficient way of removing Ph3P=O and succinimide. You just triturate the evaporated reaction mixture in diethyl ether, or better yet petroleum ether if the alkyl bromide happens to be well soluble in it, and filter trough a couple of cm of silicagel a'la flash filtration/chromatography (but mind that if there is unreacted Ph3P present it will pass trough; only polar side products like Ph3P=O and succinimide are retained which are also quite insoluble in Et2O and petroleum ether anyway).

Sergei_Eisenstein - 15-3-2008 at 09:04

They (= academically scholared chemists) told me that Ph3P=O can only be removed by column chromatography. I should have known about this quick-and-easy short column trick

I thought Ph3P is rather easily oxidized by oxygen, so maybe traces will easily oxidized if you let your product dry for, say, 2 weeks?

vulture - 15-3-2008 at 09:37

Quote:

I thought Ph3P is rather easily oxidized by oxygen, so maybe traces will easily oxidized if you let your product dry for, say, 2 weeks?

I don't think so. We have rather big jar of PPh3 which holds its own in air quite well. Zerovalent transition metal complexes of PPh3 tend to be very air sensitive, however.

[Edited on 15-3-2008 by vulture]

Sandmeyer - 27-3-2008 at 13:55

Quote:

Originally posted by Sergei_Eisenstein
They (= academically scholared chemists) told me that Ph3P=O can only be removed by column chromatography. I should have known about this quick-and-easy short column trick

I thought Ph3P is rather easily oxidized by oxygen, so maybe traces will easily oxidized if you let your product dry for, say, 2 weeks?

I use short silica plug (like a filter) on many occasions. Provided that you can develop a mobile phase system where the impurity is a non-moving spot (post-Wittig or post-Lawesson* among other examples) and the goodies migrate relatively fast. Then you just rinse the goodies out.

*: http://www.organic-chemistry.org/namedreactions/lawessons-re...

[Edited on 27-3-2008 by Sandmeyer]