Bandil (Hive Bee)
10-24-02 04:46
No 372127
      formylation of 2-methylhydroquinone  Bookmark   

Hi!

Swib was looking at the various possibilities for formylating 2-methylhydroquinone, to give 4-methyl-2,5-dihydroxy-BA.

The really good choice would obviously bee the gatterman or the POCl3/DMF formylation, but swib is not thrilled about using either POCl3 or HCN... So, he was looking at some alternate routes for formylations. Here is the routes he is looking at(all the schemes , except the last,are from rhodiums page):

Reimer-Tiemann formylation of 4-Methoxyphenol (Org. React. Vol 28 p16)
Would it be possible to use tolulhydroquinine instead of the 5-methoxyphenol and get the same yeild??

Modification of Vilsmeier-Haack reaction: US Pat
5599988, using oxalylchloride in DMF

Same question as above... and: is it vital to control the temp. ranges as precise as in the patent??


Reimer-Tiemann formylation of 4-Methoxyphenol (Arch. Pharm. 308, p341 (1975))

Basicly the same as the first one, but a little modified. Same questions...

Blazevic and Kolbah: Synthesis;1979;3;161;Hexamethylenetetramine, A Versatile Reagent in Organic Synthesis pp.6
Describes how to formylate using trifluoro aceticacid/HTMA in fair yeilds. How would you suspect this reaction would go given the tolulhydroquinon as a starting material?

Any comments from some fellow bees??

Thanks alot!

Regards
Bandil


 
 
 
 
    Rhodium
(Chief Bee)
10-24-02 06:06
No 372143
      If you can aquire POCl3, it is really not as ...  Bookmark   

If you can aquire POCl3, it is really not as noxious as its reputation says.
 
 
 
 
    Bandil
(Hive Bee)
10-24-02 06:17
No 372146
      It is possible to aquire, but its labeled very ...  Bookmark   

It is possible to aquire, but its labeled very toxic and thereby requires a permit from the gov. and the added attention thereof...

But swib was looking at the chloromethylation of the tolulhydroquinine and the following HMTA treatment to give the Benzaldehyde... I know its not possible to do with 2,5-dihydroxy-benzene, but it is with the mono brominated version of it... How about the methylated version(as in the tolulhydroquinone...)? Would that work with the classic chloromethylation?

Thanks!

Regards
Bandil
 
 
 
 
    Nemo_Tenetur
(Hive Bee)
10-25-02 00:50
No 372478
      POCl3 synthesis  Bookmark   

Some months ago I had the same problems (POCl3 aquisition), Ive synthesized it in a good yield (85-90% purified) by simple fusion followed by distillation of P2O5 and PCl5.
Yes, PCl5 is also a C-weapon precursor, but several years ago Ive gotten some kilos PCl5 unregistered.
 
 
 
 
    Bandil
(Hive Bee)
10-25-02 01:52
No 372496
      Well... the idea was actually to perform a synth ...  Bookmark   

Well... the idea was actually to perform a synth of DOM w/o POCl3 as many bee's are reluctant to use this. Thats why swim is interested in the chloroformylation...
 
 
 
 
    Chimimanie
(Stranger)
10-28-02 15:22
No 373796
      You can try to synth benzoquinone see post 362456 ...  Bookmark   

You can try to synth benzoquinone see post 362456
 Post 362456 (poix: "Quinones from phenols or hydroquinones with H2O2: ...", Law and Order)
(try the catalytic one, and post your result here)
 
alkylate it like in
http://www.orgsyn.org/orgsyn/prep.asp?prep=cv6p0890,
 
reduct with Na2S2O4 (just wash your ether layer with the quinone with an aqueous layer of Na2S2O4 until there is no more color),
 
methylate your alkylhydroquinone,
 
do the chloromethylation I just posted
Post 373715 (Chimimanie: "Synthesis of 2-Chloromethyl-5-alkyl-DMB", Methods Discourse)

and now process it like you want:

if you want the 2C-D/E/P/B:

just swap it with cyanide like in
../rhodium/chemistry /2c-d.html
reduct the nitrile with cobalt/NaBH4
Post 373778 (Chimimanie: "Nitrile reduction using Cobalt Chloride and NaBH4", Methods Discourse)

If you want the amphet counterpart do a grignard on the chloride
http://www.orgsyn.org/orgsyn/orgsyn/prepContent.asp?prep=cv1p0471
react it with acetonitrile
../rhodium/chemistry /phenylacetone.html#grignard to get the corresponding P2P.


PS: I have never saw a formylation on alkyl hydroquinones, only on their dimethyl ether counterparts, so you must methylate your HQ before trying to formylate it i think.