Novel Method to P2Ps: Diazoepoxidation.

[PrimoPyro]

Hi. By now everyone should be used to wacky ideas from me. Here's one I had this morning. Tell me what you think.

Diazoalkanes react with aldehydes to give epoxides, or in the case of diazomethane, sometimes other products, too. Epoxides can easily be rearranged to ketones using H2O/H2SO4.

Simply enough: Reaction of diazoethane with a benzaldehyde, substituted or not, would give the propenyl epoxide, which would then be worked up as usual to give the phenylacetone, substituted or not. Of course, alternately you could prepare the diazoalkane of benzaldehyde and react it with acetaldehyde to get the exact same product, but since the diazoalkanes are produced from the aldehydes, it is really trivial which one you choose.

Ive been wondering about this for a couple days, and kept wondering how the hell one would make diazoethane, CH3-C(H)=N2. I read this this morning, on pg. 1519 of March's 5th. I love this book.

When hydrazones are oxidized with HgO, Ag2O, MnO2, lead tetraacetate, or certain other oxidizing agents, diazo compounds are obtained: R2C=N-NH2 --HgO--> R2C=N=N

Then it goes on about other variations, which are interesting, but not applicable here, such as transformation of benzyl hydrazones to give nitriles: ArCH=NNH2 ----> ArCN, etc.

So, this seems easier to me than using nitrosylurea or the very expensive diazald reagent. That's a good semilong list of oxidizing agents. HgO is not too hard to come by, but MnO2 is much easier even. The big pro about HgO is that elemental Hg is the product, and is very easy to remove, since the reaction is a dehydrogenation of the hydrazone, the products are H2O and liquid Hg metal. Clean, I like it.

There are all kinds of really cool possibilities incorporating diazo compounds. Im really starting to like their reactions (yes I am aware of how icky diazomethane is, I'll probably never use it, but I still want to discuss it).

Diazoalkanes will alkylate phenol groups, they will cause "ring expansion" of aldehydes and ketones to give epoxides, they will alkylate secondary amines very well, they give aziridines upon reaction with imines, they are somewhat water tolerant (nice feature lol).

So for instance, you have the reaction proposed above, or you could react acetaldehyde with methylamine to get the imine, then react the imine CH3-CH=N-CH3 with diazomethane with Yb(OTf)3 catalyst to get 1,2-dimthylaziridine, or you could react 2-methylaziridine (commercially available!) with diazomthane to alkylate the nitrogen to get 1,2-dimethylaziridine.

(dimethylaziridine is then reacted with phenylmagnesium halides to make a methamphetamine in one reaction.)

Also, I am wondering if there is a way to make aryl hydrazines from arylamines. Basically Im looking for a reaction that does this: Ar-NH2 ---> Ar-NH-NH2. Directly above the previously quoted text on pg. 1519, it says:

Ar-NH-NH-Ar ==NaOBr==> Ar-N=N-Ar

N,N'-Diarylhydrazines are oxidized to azo compounds by several oxidizing agents, including NaOBr, HgO, K3Fe(CN)6 under phase-transfer conditions, MnO2 (this reaction yields cis-azobenzenes), CuCl2, and air and NaOH. The reaction is also applicable to N,N'-dialkyl- and N,N'-diacylhydrazines. Hydrazines (both aryl and alkyl) substituted on only one side also give azo compounds, but these are unstable and decompose to nitrogen and the hydrocarbon:

Ar-NH-NH2 ---> [Ar-N=NH] ---> ArH + N2

Well, I seem to recall Foxy2 once asking how to remove an nitro group from an aromatic ring once, and Rhodium had replied to reduce it to an amine and diazotize the amine, followed by reaction with hypophosphoric acid to reduce it off the ring. (yes I have a decent memory dont I?   )

Well I happen to like this method better if someone could just tell me a good way to easily turn ArNH2 into ArNHNH2.

The only way (so far) that I can think of is to react the aniline with carbamic acid, H2N-COOH, to make the carbamate salt, which dehydrates to the substituted urea, then use the Hypohalite Degradation (foxy2 also posted a ref for this, my thanks goes to foxy2) to get the hydrazine from that. Is there an easier way?

I find this all to be very very interesting. I find any procedure for removing any group off an aromatic ring interesting, because this is not something that is so easy to do without expensive reagents like Pd hydrogenation, etc.

PrimoPyro
Will perform sexual favors for females in exchange for 1,2-dimethylaziridine. PM for details.

[PrimoPyro]

I've found a couple more truly kick ass reactions someone might like to read about.

First, to answer my own question, yes there is a much easier way to prepare phenylhydrazines from anilines than the guess I had written above utilizing carbamic acid. Page 1556 of March's 5th cites a simple reaction between a diazonium salt and sodium sulfite.

This essentially means that Rhodium's suggestion to reduce the nitro group to an amine, and diazotise it, remains the same. But the hard to get hypophosphorous acid can now be replaced by simple sodium sulfite, Na2SO3. The result is the same.

Next cool thing, what if you wanted to turn an aromatic amine into a nitro group? How would you do that? Oxidize it? That probably would be messy. Page 936:

Nitro-de-diazoniation

ArN2+ + NaNO2 --Cu+--> ArNO2

Nitro compounds can be formed in good yields by treatment of diazonium salts with sodium nitrite in the presence of cuprous ion. The reaction occurs only in neutral or alkaline solution. This is usually not called the Sandmeyer reaction, although it was discovered by Sandmeyer. The BF4- ion is often used as the negative ion to avoid competition from the chloride ion. The mechanism is probably like that os 14-25. If electron-withdrawing groups are present (on the ring), the catalyst is not needed; NaNO2 alone gives nitro compounds in high yields.

Neat.  

And look at this, next page, 937. Tosyl chloride is useful, no? Kinda expensive, maybe you don't want to order it? Well there's always this:

Replacement of the Diazonium Group by Sulfur-Containing Groups

ArN2+ + SO2 ==CuCl2/HCl==> ArSO2Cl

Diazonium salts can be converted to sulfonyl chlorides by treatment with sulfur dioxide in the presence of cupric chloride. The use of FeSO4 and copper metal instead of CuCl2 give sulfinic acids (ArSO2H).

Also, for those of you interested in 2C-T compounds, sulfonyl halides can be reduced to thiols, ArSH, with LiAlH4. Sulfonic acids can be reduced to thiols with triphenylphosphine and either I2 or a "diaryl disulfide". Ar-S-S-Ar? Probably.

PrimoPyro

[EDIT]Simple mistake on my part. Addition of Na2SO3 to a diazonium salt produces the phenylhydrazine, which must then be reduced to the arene. So it is not exactly like rhodium's suggestion, but is one step longer.

Will perform sexual favors for females in exchange for 1,2-dimethylaziridine. PM for details.