Author Topic: Benzaldehydes: from nitro to hydroxy in one step!  (Read 8143 times)

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Rhodium

  • Guest
Thanks!
« Reply #20 on: April 26, 2003, 11:30:00 AM »
Thank you, "falls erforderlich" means "if needed", so the translation is correct. It has now been added to mma.html

catastrophe

  • Guest
Nice Idea
« Reply #21 on: April 26, 2003, 03:37:00 PM »

1. Nitrate p-xylene,
2. Oxidize with MnO2 (or Oxone) to 4-methyl-3-nitro-BA (the methyl ortho to NO2 is deactivated and won't get oxidized);
3. Then - as above.




That is an excellent idea Antoncho!

ArCH3 + 2MnO2 + 2H2SO4 --> ArCHO + 3H20 + 2MnSO4

This will probably have to be done with some acetic anhydride to prevent oxidation of the aldehyde through the diacetate. And, as you stated, the -CH3 ortho to the nitro group will most probably indeed be unaffected. Very nice idea!

As for as the nitration of aldehydes, SWIM is aware that the aldehyde moiety is strongly meta directing to nitration. Phenols are strongly ortho directing, so this would be great for vanillin. Isolation of the diazonium salt and reaction with MeOH should yield syringaldehyde. About nitration, under what conditions should it be performed to prevent oxidation of the aldehyde??? If one wanted to attempt this on say Piperonal to obtain 2-nitro-4,5-methylenedioxybenzaldehyde would the strongly acidic conditions in the diazotization cleave the methylenedioxy bridge? Strongly acidic conditions are absolutely required to prevent coupling reactions of the diazo salt with the unreacted amine.

ANY thoughts would be appreciated. Thanks Antoncho!


catastrophe

  • Guest
WOW, this thread has really been dominated for
« Reply #22 on: April 26, 2003, 03:40:00 PM »
WOW, this thread has really been dominated for an MMAI synthesis. Is that all everyone's interested in? Didn't know neurotoxicity was becoming that popular.

Chimimanie

  • Guest
Hehe
« Reply #23 on: April 26, 2003, 04:09:00 PM »
Yes it is directed to MMA(I)

neurotoxicity is not fun, and making legal analogs of popular drugs is fun....

MMA seem very interesting, it merit some more research :P

catastrophe

  • Guest
Other interesting ideas other than 3-MeO-4-Me-A
« Reply #24 on: April 26, 2003, 04:28:00 PM »
SWIM was pondering while running through Rhodium's page, and what about these ideas...

2C-CN?
------
From Rhodium's we have 4-nitro-2,5-Dimethoxybenzaldehyde

https://www.thevespiary.org/rhodium/Rhodium/chemistry/4-alkylthio-25-dmb.html

...

2,5-Dimethoxy-4-nitrobenzaldehyde (1)

2,5-dimethoxybenzaldehyde (3.00 g, 18 mmol) diluted in AcOH (5mL) was treated with 12 mL 65% HNO3 in small portions, with good stirring and cooling in a water bath. The reaction mixture, partially crystallized, was left at room temp around 10 min and then it was diluted in 50 mL water. Filtering, washing with water and drying gave 3.27g (86%) of product, the majority being 3,6-dimethoxy-2-nitrobenzaldehyde (2), 4-nitro- 2,5-dimethoxybenzaldehyde (1) in ~20% yield, and a small quantity of a third unidentified isomer. The crude product was fractionated by chromatography in a silica gel column with ethyl acetate as eluent, from which firstly the minor product (1) appeared, which after recrystallization from IPA had a mp of 163-164°C (lit. 163-165°C [7]).




Now we reduce to the 4-amino compound, diazotizate, and react our diazo salt (the sulphate) with a solution of the cuprous cyanide-sodium cyanide complex, NaCu(CN)2, to get our nitrile. Pretty simple compared to the current method.

How about p-fluoroamphetamine?
-------------------------------
p-nitrobenzaldehyde is reduced to the p-amino compound. Now we diazotize the aromatic amine in the presence of fluoboric acid, when the fluoborate precipitates. Heating the DRY fluoborate will give the fluoro derivative and some BF3 too, no? Something like this...

ArNH2 + 2HBF4 + NaNO2 --> [ArN2+]-BF4 + NaBF4 + 2H2O

Now, obviously if we heat the fluoborate we'll get the fluoride compound and some boron flouride as well.

Also, if you wanted a -Cl or a -Br instead, you could just do a Sandmeyer on the diazonium salt.
And boy!, this would be a GREAT way to put -I on the ring. Just add potassium iodide to an aq. sol. of the sulphate and heat.

Anyways diazo compounds are really useful. Thanks for bringing this thread up Antoncho; a lot of the times here at The Hive, a really reputable bee needs to bring something up in order for the less reputable bees to get their ideas heard. So thanks again! :)


Rhodium

  • Guest
Sandmeyer not working on unprotected aldehyde
« Reply #25 on: May 04, 2003, 08:45:00 AM »
Catastrophe: You cannot prepare p-Fluorobenzaldehyde that way. First, the aminoaldehyde is very polymerization-prone as is, and that gets  worse when diazotizing, and then infinitely horrible in the presence of HBF4 - black, toxic tar galore! And please, stay on topic - if you want to discuss the above ideas of yours, please re-post your post above in another thread, this one is dedicated to MMA and its precursors.

Back on topic: Here are two references related to the discussion, posted by Antoncho in a no longer existing post in the "Wanted References" thread:

Nitration of benzaldehyde:

Patent US1509412



Diazotization of m-amino-BA:

http://orgsyn.org/orgsyn/prep.asp?prep=cv3p0564


cattleprodder

  • Guest
? for Rhodium
« Reply #26 on: May 14, 2003, 03:59:00 PM »
Could this method be used to convert piperonal or
3,4-methylendioxybenzoic acid (from safrole and KMnO4) to myristicinaldehyde?

Rhodium

  • Guest
Not MMDA, but MMDA.2
« Reply #27 on: May 14, 2003, 04:43:00 PM »
No, piperonal undergoes aromatic substitution (nitration etc) in the 6-position (see

https://www.thevespiary.org/rhodium/Rhodium/chemistry/tma2.vanillin.html

) and thus it will not work. You could however use the procedure to synthesize 6-MeO-3,4-MDA (also called 2-MeO-4,5-MDA or MMDA-2).

GC_MS

  • Guest
sesamol
« Reply #28 on: May 14, 2003, 11:22:00 PM »
I have had the idea once to synthesize sesamol from benzedioxol via diazotation. In my opinion, the B-V reaction of piperonal sounded to wasteful  ::)
I never went any further then the nitration of benzedioxol, which really was no problem. Stupid as I am, I didn't write down the reaction details, but I remember the solvent being GAA and the yield was to be found in the 90s%. GC/MS analysis indicated the presence of ca 1% of a (tentatively identified) dinitrated product, but aside this impurity, everything looked OK. Colour test with concentrated sulfuric acid also matched the literature references in Beilstein (was it red? Not of importance now...).
The idea behind this was to find a precursor for 5-alkoxy-piperonal. Sesamol can be methylated, ethylated... and subsequently thrown in a Vilsmeier-Haack reaction mixture to magically yield 5-alkoxypiperonal.
Bromination of the benzedioxol worked out well, but substitution of the Br by OH (Cu catalyzed) seemed to be a problem... Maybe I should try to find my nitrated benzodioxol in the fridge and look for what it does with the one-pot thing...  :)


Rhodium

  • Guest
3-NO2-4-Me-BA -> 3-MeO-4-Me-BA (53% Yield)
« Reply #29 on: May 23, 2003, 04:36:00 PM »

Post 434913

(GC_MS: "3-methoxy-4-methylbenzaldehyde", Methods Discourse)

imp

  • Guest
General Info.
« Reply #30 on: October 15, 2003, 11:19:00 PM »
Earlier in this thread the question of why an acidic aqueous solution should be used to decompose the diazonium salt into a phenol was brought up. A very nice response was given...

Post 428585

(GC_MS: "diazo salt", Chemistry Discourse)



A strong acidic reaction environment prevents hydrolysis of the diazo salt and reaction of the formed phenol with the diazo salt to hydroxyazo substances. Since the reaction between the formed phenol and the diazo salt can ruin your yields, the phenol is sometimes removed via steam distillation during the reaction.




SWIM just wanted to add a few useful points to this. Yes, diazonium salts react with phenols in weakly acid, neutral, or alkaline solution, to form highly coloured azo compounds. This coupling reaction generally causes substitution in the position para to the hydroxyl group. If the para position is occupied, coupling takes place in the ortho position. If the para position and both ortho positions are blocked, coupling usually does not take place, although occasionally a group such as the carboxyl group at the para position may actually be displaced. However this sort of coupling is only seen in highly activated phenolic rings. 

As far as replacing the diazo moiety with an alkoxyl group, certain complications arise. Firstly, this type of alkoxylation gives a mixture of two products - the alkoxy and the hydroxyl group. Using ethanol as the alcohol for replacement usually leads mainly to the hydroxyl...

[ArN2+]-OSO2H + CH3CH2OH ---> ArH + N2 + H2SO4 + CH3CHO

[ArN2+]-OSO2H + CH3OH ---> ArOCH3 + N2 + H2SO4

(If using MeOH, you might be able to smell for the presence of any formaldehyde generated)

Furthermore, an acidic environment must be created in order to prevent side-rxns. MeOH saturated with HCl should be acceptable, as it will remain anhydrous and help increase yields. Experimentation is heavily warranted in order to find answers.