Author Topic: Asprin as useful precursor?  (Read 3820 times)

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ApprenticeCook

  • Guest
Asprin as useful precursor?
« on: August 15, 2004, 05:56:00 AM »
My apologies:
1) if the wrong forum was used (posted in chem discourse)
2) if its crap, im very tired...

I dont know if this would work but i thought of it when i grabbed my packet of asprin.....

1 - Asprin (2-acetoxybenzoic acid) --> 2-acetoxy-4-bromobenzoic acid (Br2 + AlCl3)

2 - 2-acetoxy-4-bromobenzoic acid --> 4-bromo-2-hydroxybenzoic acid (dil. H2SO4)

3 - 4-bromo-2-hydroxybenzoic acid --> 4-bromobenzene-1,2-diol (?)

4 - 4-bromobenzene-1,2-diol --> 4-bromo-1,2-methylenedioxybenzene (KF, DMF, CH2Br2 ?)

My concerns:
1) If the halogenation step is wrong... it may be effected by the following steps after its inclusion.
2) the decarboxylation step, i have not thought about this step yet....
3) A dream would be to use haloacetone and make 2-acetoxy-4-(2-oxopropyl)benzoic acid instead of leaving the halogen there, would the ketone be affected with the steps after its inclusion?
4) if the idea is the product of not enough sleep and to much drug use on my part.

Just a thought to inspire something, if only flames, well you get that....

-AC


longimanus

  • Guest
maybe not that useful
« Reply #1 on: August 15, 2004, 09:55:00 AM »
It`s not very likely to brominate Aspirin to 4-bromoacetylsalicylic acid; the main product is 5-bromoacetylsalicylic acid due to the electronic effects of the carboxy and acetoxy group.
 That would not be a problem if the decarboxylation step works. But since salicylic acid is decarboxylated to phenol it`s logically to conclude that 4(or 5)-bromosalicylic acid is decarboxylated to m- or p-bromophenol. Any ref for step #3?

ApprenticeCook

  • Guest
The products of the bromination step would be...
« Reply #2 on: August 15, 2004, 11:46:00 AM »
The products of the bromination step would be a mix of 4 & 5, i forgot to mention that, but seeing as in the long run (providing the position does not effect any further steps) it didnt matter i didnt see reason to mention it.

The decarbox was the problem, how can you make it leave an OH group? prob cant... in that cas skip bromination and decarbox to phenol, then OH are ortho/para so make to 1,2-benzenediol???? then as per rhodiums site synth catchetol --> safrole?

Ref for step three? well i dont know if it works with the halogen there but the steps are on rhodiums page regarding the increase in yields of methylation reaction with KF as catalyst in DMF solvent, using CH2X2 as addition group.
If it doesnt work just leave out bromination and methylate, but this provides a problem, NBS must be used to brominate in the correct position, the simple AlCl3/HBr will brominate ortho/para (para would be ok, but i think ortho is the MAJOR product).

-AC


Nicodem

  • Guest
Aspirin? Yes please!
« Reply #3 on: August 15, 2004, 12:16:00 PM »
I must admit that sometimes I also can't avoid looking at aspirin as a potentially useful precursor. Though, in my mind it usually plays the role of a 4-X-2,5-diMeO-PEA precursor.

I’m also unaware of any oxidative decarboxylation that would yield a phenol from a benzoic acid and like longimanus I’m also convinced that the bromine would attack the position 5 of (acetyl)salicylic acid, but that is just perfect in any case.
It might be possible to nucleophylicaly substitute the bromine with a methoxy with the

Post 503332

(Rhodium: "Methoxylation of Aryl bromides cat. by Cu(II)-CO2", Chemistry Discourse)
method (if it only did not require an autoclave) or some of the other similar methods that seam to work so good with 5-halogen-vaniline (like MeONa/CuCl/DMF:

https://www.thevespiary.org/rhodium/Rhodium/chemistry/345-tmba.html

).
The product, 2-hydroxy-5-methoxy-benzoic acid, could be methylated to 2,5-dimethoxy-benzoic acid, this then transformed to the acid chloride (or etherified with MeOH). From here on, the reactions required were already discussed in

Post 490756

(Bandil: "Benzoylchloride to something usefull", Chemistry Discourse)
.


longimanus

  • Guest
wait, wait, wait
« Reply #4 on: August 15, 2004, 12:17:00 PM »
First - the product will be mixture of every possible bromoderivative but the main product will be the 5-bromo.
 
 Second - it doesn`t make any sense extracting Aspirin tablets and decarboxylating the acetylsalicylic acid when you could simply buy phenol! ::) . Just doesn`t worth it.

 Third - Aaahm, actually, step #3 was decarboxylation but you`re giving me references for step #4. ;)

 And, which compound are you talking about in the last paragraph? I just couldn`t really understand.

 And at the end - an idea. One could possibly reduce the carboxy group to the corresponding benzyl alcohol (by your suggestion - 1-[4-hydroxy-3-(hydroxymethyl)phenyl]propan-2-one) and use it as an alternative precursor for the MDA analogue from

Post 499371

(camxyl: "Benzodioxin MDA analogue?", Novel Discourse)
. Just an idea.

Edit: It seems that Nicodem was a minute faster than me. And his idea is someway better than mine - camxyl`s benzodioxin is probably inactive. But here a problematic step will be the 4-substitution that will transform the product to something other than 2,5-DMA. Or maybe not so problematic? ;)

ApprenticeCook

  • Guest
learn to read AC.....
« Reply #5 on: August 15, 2004, 03:23:00 PM »
Yes it will be a mix of every subs position with bromo but a mix of 4 & 5 are ok to use further on so its just eh other % you need to get rid of.... which are only small

i didnt want to decarbox asprin to phenol i wanted to get to dihydroxy... unless you can buy them phenol straight up and add another OH group ortho... how to dercarbox and leave an OH group in its place was what i was asking....

Sorry i didnt read properly... i put the (?) for #3 because i didnt have refs i was wondering how it could be done.... the brackets for the other steps contain info i know how to and were included to give an idea of process.

are you talking about myconcerns #3??? i was talking about replacing the bromination step with an addition of chloroacetone so the end product would be MDP2P instead, as i said, it would be a dream....
Or are you talking about my reply?
NBS - N-bromosuccinamide (sp?) its on rhodiums synth page for catchetol --> safrole.
If you leave out the bromination step and just go ahead and methylate the dihydroxybenzene you can just use HBr and AlCl3 to brominate the ring in major yields... the methoxy groups are ortho/para directing, ortho is the major product but the para would be fine (i think para in this system end up ~20% of the yield???.

2,5-DMA looks budget anyway as per:

http://www.erowid.org/library/books_online/pihkal/pihkal054.shtml


So i would rather not end up with this....

Crap, i dont think this is really going anywhere, much the same as my failed thought about grinards --> ghb...
Oh well, leave the asprin on the shelf where it should be i guess....

-AC


longimanus

  • Guest
uhhh
« Reply #6 on: August 15, 2004, 07:06:00 PM »
So much misunderstanding!
 Catechol(not catchetol) -> safrole is a promising route but I still don`t see any possibility for converting Aspirin to catechol - maybe except for Aspirin -> salicylic acid -> phenol -> 2-hydroxybenzenesulfonic acid -> catechol - not really something that makes sense.
 
 Yes, and about 2,5-DMA - one could always acylate N-trifluoroacetyl-2,5-DMA and reduce to 4-alkyl-2,5-DMA. Just another idea.

Nicodem

  • Guest
Excuse me…
« Reply #7 on: August 15, 2004, 07:42:00 PM »
…but where did you get the idea that the 4-bromo-salicylic acid would be the second major product. I wish everybee would finally read

https://www.thevespiary.org/rhodium/Rhodium/chemistry/eas-rate.html

and understood the concept of directing the electrophylic substitution by activation and deactivation. There are only two positions that are more or less equally activated in (acetyl)salicylic acid, the position 3 and 5. So you would end with these two bromo products. I think 5 would be somewhat prevalent when brominating aspirin due to steric hindrance of the acetoxy group, however there are sometimes surprises. Like the possibility of the acetoxy actually promoting the bromination at its ortho position by forming an hexagonal complex with the Br+.

A search on Google revealed this sentence:
Other strategies, such as the direct bromination of salicylic acid, which is reported to give only the 3-brominated isomer (10), gave us mixtures of the 5-bromo- and 3,5-dibromo- products and never the desired isomer.

From the otherwise (for me) inaccessible full text of:
A highly efficient strategy for the synthesis of 3-substituted salicylic acids by either directed ortho-lithiation or halogen–metal exchange of substituted MOM protected phenols followed by carboxylation.
Canadian Journal of Chemistry, vol. 79, no. 11 (2001) 1541-1545.

http://www.ingenta.com/isis/searching/Expand/ingenta?pub=infobike%3A//nrc/cjc/2001/00000079/00000011/art00008


So, if anybee has access to this publisher, please upload it.

BTW, Aprentice you wrote that you “can just use HBr and AlCl3 to brominate the ring in major yields” already twice. I just want to remind you, that you need bromine (Br2) for brominations and not HBr (unless if combined with a suitable oxidant). And you don’t need AlCl3 since both aspirin and salicylic acid are already reactive enough.
I also wish to see more references to the literature in this thread or it will soon became useless.


ApprenticeCook

  • Guest
I think its already useless....
« Reply #8 on: August 16, 2004, 05:18:00 AM »
I think its already useless....

Anyway in the long run should it work to an extent its usefull, the cost of initial precursor aquisition is quite large....

Ahh well.
Thanks for entertaining the idea anyway.
-AC


roger2003

  • Guest
Aspirin as Precursor
« Reply #9 on: August 16, 2004, 01:14:00 PM »
See:

Post 481597

(roger2003: "From Aspirin to Piperonal", Newbee Forum)



longimanus

  • Guest
let`s talk about money
« Reply #10 on: August 16, 2004, 06:31:00 PM »
Nice synthesis, roger2003, but let me remind you that 100 g salicylaldehyde cost ~10 euro and the same quantity salicylic acid - ~35 euro. Also - catechol: 250 g - ~10 euro.

roger2003

  • Guest
Aspirin
« Reply #11 on: August 16, 2004, 07:31:00 PM »
But the question was:

Asprin as useful precursor?  ;)


ApprenticeCook

  • Guest
Thanks roger, The question was as a usefull...
« Reply #12 on: August 17, 2004, 01:54:00 AM »
Thanks roger,

The question was as a usefull precursor but coming into this fact, for it to be truely usefull it has to be cost effective aswell.
I pulled the bottom out of my own thread, but thanks for the link ill check it out.

-AC