[user17625]

I attempted to synthesize azoxymethane by following the synthesis for azoxybenzene where the benzyl -R group was substituted with a methyl group thus my start material of  was nitromethane instead of nitrobenzene in the synthesis procedure below.  My modifications to the azoxybenzene procedure are in brackets [].  It didn't work in producing the slightest amount of azoxymethane.  

First off, I confess I did fully understand the synthesis of azoxybenzene, such as what is the purpose of sodium hydroxide, and especially dextrose.  

Secondly, Any ideas on a working or proposed synthesis of azoxymethane, and if it involves aniline, where can I get aniline?


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The following alternative procedure for preparing azoxybenzene is convenient.

In a  three-necked flask fitted with a reflux condenser and an efficient stirrer there are placed 60 g. of sodium hydroxide, 200 cc. of water, and 40.6 g. (33.9 cc., 0.33 mole) of nitrobenzene. [20.14g (17.715cc, 0.33 mole) nitromethane]

 The flask is immersed in a water bath kept at 55–60°, and 45 g. (0.23 mole) of dextrose is introduced in portions, with continuous stirring, in the course of one hour.

The temperature of the bath is then raised to 100° [80deg for 8 hours] and kept there for two hours.

The hot mixture is poured into a 2-l. long-necked flask and steam-distilled to removed nitrobenzene and aniline.

This requires some twenty minutes, during which time about 2 l. of distillate passes over.

When the distillate is clear, the residue is poured into a beaker and cooled well in an ice bath.

The azoxybenzene, which solidifies, is collected, the lumps are ground in a mortar, and the product is washed with water and dried.

The yield of material melting at 34–35° is 26–27 g. (79–82 per cent of the theoretical amount).

Crystallization from 15 cc. of methyl alcohol gives material melting at 35–35.5° with 90 per cent recovery.

(Nicholas Opolonick, private communication. Checked by Louis F. Fieser and M. Fieser.)

[Dan]

The boiling point of azoxymethane is <100^oC, so it will have evaporated during your steam distillation step.

I would assume that dextrose is the reducing agent.

[user17625]

Thank you for responding.  I didn't even consider that role for dextrose.

Yes, that is correct about the boiling point.  That is why I reduced the temperature bath below 100deg and processed for 8 hours instead of two hours.  I actually then did a fractional distillation and collected the distillate up to 100degC instead of the steam distillation.  The distillate was water without even trace amounts of azoxymethane.  I stopped at that point.  


Is it possible that azoxymethane stayed in the bath with some elevated boiling point phenonmenon?

I considered using a (condenser cooled) reflux apparatus in the event that then smaller molecule nitromethane still needs 100deg for the reaction to proceed instead of 20 deg less for 4 times as long.  (Not too happy about the idea of possibly breathing the resultant residual vaporized azoxymethane however.  Maybe a packed column will eliminate that problem.)

Or maybe the whole idea of trying a synthesis and with a substituted a methyl -R group for the benzene is not valid?
 
Any suggestions, anyone?

[OC pro]

I would be careful with that stuff. Azoxymethane is highly carcinogenic. Aldrich lists it under chemicals for "Cancer Research". Used to induce cancers in mice. Vapours of azoxymethane doesn´t sound too good. I think it would have come out with the water (azeotropically).

Give this sh** up. It´s not worth...

[user17625]

This is to be used to study cancer.  

Can I get some help on the synthesis?

[AndersHoveland]

not sure if this will be helpful:
https://sites.google.com/site/energeticchemical/hydrazines-by-oxidation

Azomethane can probably be oxidized to azoxymethane by one of the following methods which are known to oxidize pyridine to pyridine N-oxide:

Typically trifluoroacetic acid with H2O2 is used, but there are several other methods.

A catalyst can be used to allow the H2O2 to oxidize the hetrocyclic nitrogen.
Selective mono N-oxidation of substituted pyrazines in good yields using 30% dilute H2O2 as an oxidant with a specially prepared titanium silicate catalyst is possible.  

Preparation of the Catalyst
Add a solution of titanium peroxide to ethyl silicate (with or without an organic solvent) to obtain a gel. Hydrolyze the homogeneous gel previously obtained, by adding an organic base to the gel. The ammount of organic base should be only 6-15% of the ammount of silica gel. Next, add deionised water after the yellowish-white color of the gel begins to turn into a greenish-white color. Stir the greenish-white gel for about 1 hour, then heat the gel in a pressure cooker at 100 -110 C. The gel must be constantly heated in this way for at least 20 hours. Further heating, up to 2 days, is preferable. This will result in a solid composite product. Separate out the resultant solid composite material, dry, and bake at a 350-500C temperature to obtain the final product. This is a catalyst and so only a small quantity need be prepared. The organic base should be an organic amine with lots of bulky organic groups on it, either a tri- or tetra-alkyl amine, such as tetrapropyl ammonium hydroxide. Alternatively positively charged coated silica particles can be used instead of the ethyl silicate. These can be prepared by mixing an aqueous colloidal silica with stabilized basic aluminum acetate. The aluminum composition is stabilized with a small quantity of boric acid, which controls the hydrolysis of the aqueous solution of basic aluminum acetate.

The catalyst produced above is known as TS-1 and is basically a porous titanium silicate crystal with a structure analogous to zeolite. TS-1 is not yet commercially available. It can also catalyze the oxidation by H2O2 of imines R2C=NH into
oximes R2C=NOH.

Methyl Cyanide Activation

methyl cyanide can activate the H2O2 so that it can oxidize the cyclic nitrogen atom.
At a pH of 8 , H2O2 reacts with CH3CN to form a peroxycarboximidic acid intermediate CH3C(=NH)O--OH. This is unstable and immediately oxidizes whatever reducing agent is in solution. If no reducing agent is present, acetamide will result and oxygen gas will escape from solution. Other nitriles beside methylcyanide also will work, possibly even addition of threads of acrylic fabric (synthetic wool) will work. An alkaline solution of a nitrile and H2O2 can also oxidize an alkene to an epoxide. I am not entirely sure that the amine will not be vulnerable however. The trifluoroacetic acid and H2O2 route are known to create an N-oxide while leaving the amine on the electron deficient (because of two nitro groups) ring unoxidized, but the strong acidity might be important in protecting the amine group. The fact that the ring is electron deficient makes the amine less vulnerable to oxidation, but I am unsure if this is enough without strongly acidic conditions. The methyl cyanide activation necessitates al
 
Note: the below was not intended to be part of this message but it could not be deleted without deleting eeveryhting else because this forum has PROBLEMS!!!!ons amine groups must be protected. One such method, designed by this site, is addition of pure actone, followed by addition of acetic anhydride. This will put both an acetyl and an isopropylene (-he amine, and the isopropylene will inevitably be oxidized to an epoxide, wasting nitrile and H2O2. These groups will hydrolyze off after the oxidation by addition of concentrated NH4OH solution, leaving the plain amine intact. This would only be relevent if using the H2O2 and titanium silicate catalyst route, since alkaline conditions would prematurely hydrolyze off the protecting groups.
 th only two nitro groups, since addition of the last nitro group will take a longer time period than addition of the first two. Then oxidize with activated H2O2 (this will not atine, and then the compound could be nitrated again, to result in about an equal mix of 6-amino-3,5-dinitro-1,2,4-triazine-1-oxide and 5-amino-3,6-dinitro-1,2,4-triazine-1-oxide. The last of whi

Using H2O2 and Acetic Acid
"Oxidation of  2,6-diamino-3,5-dinitropyridine by refluxing with a 30% solution of H2O2 in acetic acid produced 2,6-diamino,3,5-dinitropyridine-N-oxide in 80% yield."

R. Hollins, L. Merwin, R Nissan, Journal of Heterocyclic Chemistry 33, p895 (1996)

H. Ritter, H. Licht. Journal of Heterocyclic Chemistry, 32, p585 (1995)