bones (Stranger)
05-09-03 11:15
No 432279
      vanillin demethylation  Bookmark   

reference : Learmonth and Alves.  synthetic communications, 32(4) 641-49 (2002).

the above reference performs demethylation of several aromatic methyl ethers for the purpose of synthing several nitro-catechol compounds.  one of their reagents was nitro-vanillin.  i used their example of a typical procedure with vanillin - a compound not included in the paper... .but hey.. it wasnt a huge step now was it :D

the authors state that they have scaled up this proceedure to 1-50kg batches !! though i doubt they actually did.

importantly.."althoughratio of 4:1.2:1 (pyridine:Al:methylether) was commonly employed, pyridine could be satisfactorily reduced to less than 3 mol equ without deleterious effect on yield."  disco!
 
I see no reason why this synth will not extend to the safrole precursor.  though i have not tried it.

prep:

To a stired suspention of vanillin (37.3g (about 175ish mmol) in 450ml ethyl acetate at rt was added aluminium chloride (27.9g / 209mmol) in one portion.  To this sexy coloured suspention was added dropwise and with stiring pyridine (55.1g, 56.2ml, 696mmol) causing the internal temp to rise to about 45-50 oC.  The soln was then heated to reflux (77oC) for 2 hours and then allowed to cool slowly to 60oc - (i just turned off the oil bath heater and allowed it to cool veerrrryyyy slowly... though im not sure if this is necessary.. but it does make it easier to hit the temp mark).

At 60oc the rxn mix was poored carefully onto a mixture of ice and 10M HCl (200ml).  After stiring at 50oc for 1 hour the mixture was cooled on an ice bath for 1 hour and filtered. 

Filter cake washed with water and dried under high vacume for a couple of hours.  yeild = 97% (paper quotes 99.8% but .. well.. you know)

clean by nmr - reference states 95%-99.9% purity by gc-ms.... but that was too much fuckin around for me.

NOTES:

again... reference states that this prep can easily be scaled up to several kgs...

used a pyridine ratio of... what was it.. about 5ish . but over the coming days i will steadly reduce that to 2 and report yeilds and purity by NMR intergration.


now on to methylenation. :D .... KF has been reported as a commonly used catalyst for methylenation of catachols... but i cant find any laying around... also, DbromoM and DidioM are prefered by most references as they are generally more reactive and have considerably high boiling points.  but theyre wayyyy more expensive and much more difficult to abtain... DCM will be used by me.  I suspose both of the negative of DCM can be overcome by longer rxn times... however that will almost certainly reduce yeilds through unwanted side reactions regardless of the massive excess of DCM.....i suspose mixed solvents may improve this...before anything is tried... i thought it prudent to create small scale experiment conducted within a bomb at 160oc ... so... hopefully soon i will report on those... DCM, KOH, dihydroxybenzene sealed in pyrex tube and heated to 160 for (X) hours/days... but anyway.. not done yet


cheers

bones .. (sorry if there are too many typos)
 
 
 
 
    amalgum
(Hive Bee)
05-09-03 11:29
No 432283
      All this has already been documented.  Bookmark   

All this has already been documented.
../rhodium/chemistry /methylenation.html
 
 
 
 
    bones
(Stranger)
05-09-03 11:39
No 432285
      well.. yes... this procedure is considerably...  Bookmark   

well.. yes... this procedure is considerably faster - probably only to the higher boiling point of ethyl acetate compared to dcm.. and also uses considerably less pyridine than the method discribe in the JOC back in 1962.  and assuming that the authors prediction that the ratio of pyridine to methyl ester proves correct i think this is a nice improvement.

nothing dramatically new i agree... but i thought these alterations would prove useful... especially with the price of pyridine.
 
 
 
 
    amalgum
(Hive Bee)
05-09-03 15:43
No 432315
      Why not just skip pyridine altogether and use...  Bookmark   

Why not just skip pyridine altogether and use easily prepared AlI3?
 
 
 
 
    bones
(Stranger)
05-10-03 03:13
No 432398
      well cause AlI3 is apparently impractial for...  Bookmark   

well cause AlI3 is apparently impractial for large quanties... and i dont have any cyclohexane.  and inert atmospheres are a pain... there are many methods shown on rhodiums page... i just thought this was easiest.. with good yeild and low rxn times... dont use it if you dont like it.
 
 
 
 
    Rhodium
(Chief Bee)
05-11-03 20:59
No 432662
      cyclohexane substitutes  Bookmark   

Cyclohexane can very likely be substituted with regular hexane, or even standard petroelum ether.
 
 
 
 
    bones
05-12-03 06:06
      hmmmm.. yes probably...
(Rated as: UTFSE!)
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