Sciencemadness Discussion Board

Bornyl chloride as alkylating agent?

blogfast25 - 16-12-2015 at 08:57

Would bornyl chloride (below) be suitable as an alkylating reagent in Grignard reaction on acetone?



Bornyl chloride.gif - 2kB

Nicodem - 16-12-2015 at 09:29

Quote: Originally posted by blogfast25  
Would bornyl chloride (below) be suitable as an alkylating reagent in Grignard reaction on acetone?

No, you would have to prepare the organomagnesium compound from bornyl chloride first to use it in a Grignard reaction with acetone. Such raction with acetone would probably give 2-propanol as the main product (its reaction with aldehydes and ketones gives the reduced products, DOI: 10.1039/JR9310003340).* Under some conditions, the nucleophilic addition on acetone might be preferential over the reduction pathway and in such case the product would be 2-bornyl-2-propanol. Search the literature for such conditions, if they were ever discovered. If not, discover them yourself.
Quote:
Synthesis of the bornyl and fenchyl Grignard reagent. A solution of isobornyl chloride or ß-fenchyl chloride (17.2 g, 100 mmol) in THF (180 mL) was slowly added to a suspension of activated Mg turnings (2.7g,110mmol) in THF (20mL). After the addition was completed, the mixture was heated under reflux for 12 h. Prior to use, the clear solution was separated from the excess of Mg via cannula. The yield determined by titration was about 80%.
From DOI: 10.1039/B819178F



* The mechanism of the reduction is discussed in the book Progress in Physical Organic Chemistry, Volume 7, page 62 (preview available at googlebooks). It appears that at least the reaction benzaldehyde gives a little of the addition product according to this report.

blogfast25 - 16-12-2015 at 11:02

Quote: Originally posted by Nicodem  

No, you would have to prepare the organomagnesium compound from bornyl chloride first to use it in a Grignard reaction with acetone. Such raction with acetone would probably give 2-propanol as the main product (its reaction with aldehydes and ketones gives the reduced products, DOI: 10.1039/JR9310003340).* Under some conditions, the nucleophilic addition on acetone might be preferential over the reduction pathway and in such case the product would be 2-bornyl-2-propanol. Search the literature for such conditions, if they were ever discovered. If not, discover them yourself.


Quote:
Synthesis of the bornyl and fenchyl Grignard reagent. A solution of isobornyl chloride or ß-fenchyl chloride (17.2 g, 100 mmol) in THF (180 mL) was slowly added to a suspension of activated Mg turnings (2.7g,110mmol) in THF (20mL). After the addition was completed, the mixture was heated under reflux for 12 h. Prior to use, the clear solution was separated from the excess of Mg via cannula. The yield determined by titration was about 80%.
From DOI: 10.1039/B819178F



Now I'm confused, possibly because what you write is what I meant.

bornyl chloride (R-Cl) + Mg (in suitable solvent):

R-Cl + Mg === >R-Mg-Cl

R-Mg-Cl solution + acetone and after hydrolysis === > 2-bornyl propan-2-ol, a t-alcohol.

Is that what you meant too?

It would have been more accurate to ask:

1. Does bornyl chloride form an organomagnesium compound (in suitable conditions)?

2. Can this organomagnesium compound be added to acetone?

[Edited on 16-12-2015 by blogfast25]

Crowfjord - 16-12-2015 at 14:16

The organomagnesium compound will form, but rather than adding to the ketone, it might instead reduce it to the alcohol. That is pretty interesting to me. Probably has something to do with all that steric hindrance. I'll have to investigate this farther.

blogfast25 - 16-12-2015 at 16:11

Quote: Originally posted by Crowfjord  
The organomagnesium compound will form, but rather than adding to the ketone, it might instead reduce it to the alcohol. That is pretty interesting to me. Probably has something to do with all that steric hindrance. I'll have to investigate this farther.


So this reduction to the secondary alcohol wouldn't be limited to acetone either? I must admit not to know much about that type of nucleophilic addition v. reduction...

[Edited on 17-12-2015 by blogfast25]

Crowfjord - 16-12-2015 at 16:45

The reference given by Nicodem only mentions fairly hindered substrates like iso-valeraldehyde and citral. In these cases, it seems that electrons are capable of being transferred, but the squeeze is too tight for C-C bond formation. Perhaps something smaller would give the addition product instead. Whether acetone fits the criteria remains to be seen, through experimentation or maybe more scrutiny of the literature.

According to this old-timey thesis, carbon dioxide and ethyl formate give the addition products. Maybe this hints that acetone, will also?

[Edited on 17-12-2015 by Crowfjord]

chemrox - 16-12-2015 at 23:33

I doidn't see this as a potential Grignard. I thought the bulk of the molecule would limit the formation of the ether complex to negligible..However I might be wrong: http://bit.ly/1NyHQf4


[Edited on 17-12-2015 by chemrox]

User123 - 17-12-2015 at 05:36

You ARE wrong... Because you didn't read Nicodem's post. Neither did blogfast25. He has answered all questions and all subsequent questions.

[Edited on 17-12-2015 by User123]

blogfast25 - 17-12-2015 at 07:55

Quote: Originally posted by chemrox  
I doidn't see this as a potential Grignard. I thought the bulk of the molecule would limit the formation of the ether complex to negligible..However I might be wrong: http://bit.ly/1NyHQf4


[Edited on 17-12-2015 by chemrox]


Steric hindrance would reduce reaction rate, as evidenced by the 12 h period needed to form the fenchyl and bornyl organomagnesium compounds.

It would have a similar effect on the actual addition but not necessarily completely impede it. In one of Nicodem's links the bornyl Grignard reagent is added to benzaldehyde, although yield isn't high.

It kind of begs the question: 'would a chloro cyclohexane Grignard addition to acetone work and how long would that all take?'

[Edited on 17-12-2015 by blogfast25]

CuReUS - 17-12-2015 at 09:26

the preference of reducing the substrate instead of adding to it is quite common in sterically hindered grignard reagents(see adamantane reactions).
The solution is to use Li instead of Mg to form an organolithium compound,which can then be added to the carbonyl group.

blogfast25 - 17-12-2015 at 10:58

Quote: Originally posted by CuReUS  
the preference of reducing the substrate instead of adding to it is quite common in sterically hindered grignard reagents(see adamantane reactions).
The solution is to use Li instead of Mg to form an organolithium compound,which can then be added to the carbonyl group.


Is that mainly due to higher polarisation of the Li-C bond compared to the Mg-C bond or are there other factors?

karlos³ - 17-12-2015 at 12:12

You would probably have to add an aromatic solvent after the grignard reagent has formed, it looks like it might be not very soluble in Et2O.
Mostly benzene is used then if such compounds are less soluble, for further reaction with the carbonyl or other compounds, however other BTEX aromates are also employable.
The reaction works much better with the carbonyl compound then, but I don´t know more about this special substance you are after, it´s all generalised for bulky grignard reagents.
I have prepared bromomagnesiumnaphthalene and reacted it with dimethylcarbonate, and for best results the grignard(which tend to precipitate) hat to be solvated in another solvent, toluene for me, to react properly.
Nonetheless Et2O or other symmetric ethers are favored for the preparation of the grignard reagent, but blogfast25 does surely know this so I am writing this last sentence only for other people interested in this topic :).

Crowfjord - 17-12-2015 at 16:04

Quote: Originally posted by blogfast25  

Is that mainly due to higher polarisation of the Li-C bond compared to the Mg-C bond or are there other factors?


Polarization might have something to do with it, but I think that in this case it is mainly just the fact that Li is much smaller than Mg, as well as monovalent.

I found two references with Scifinder that make the 2-bornyl-propan-2-ol (dimethylbornylcarbinol), both use bornyl lithium. From Ann. chim. (Paris)(1954), Volume9, pp 51-96:
Quote:

VI (0.1 mol) in 322 cc. petr. ether treated dropwise with 0.1 mol Me2CO in 30 cc. petr. ether, and the mixt. hydrolyzed after 0.5 h. and distd. gave 4 g. dimethylbornylcarbinol, b15 112-​16°, nD18 1.4885, d18 0.9585, MRD 59.06, [α]​578 -​13.4°, [α]​546 -​16.6° (c 5​%, EtOH)​.


VI here is bornyl lithium.

CuReUS - 18-12-2015 at 04:26

Quote: Originally posted by Crowfjord  
Quote: Originally posted by blogfast25  

Is that mainly due to higher polarisation of the Li-C bond compared to the Mg-C bond or are there other factors?


Polarization might have something to do with it, but I think that in this case it is mainly just the fact that Li is much smaller than Mg, as well as monovalent..

both of you are correct,see this
https://en.wikipedia.org/wiki/Organolithium_reagent#Addition...

blogfast25 - 18-12-2015 at 08:57

Thanks all.

I had considered metal atom size too but stupidly (and temporarily) thought Li and Md are same period. Doh!