For the past few tutorials we’ve learned about carbenes, and we saw
that a very common method of carbene formation is through the decomposition of diazomethane.
Because of this, it will be useful to know how diazomethane can be synthesized,
and it will also be worth our while to examine some other applications for this compound.
Diazomethane can be synthesized from N-methyl-N-nitrosotoluenesulfonamide. Treatment
of this compound with sodium hydroxide in ether allows for the following mechanism. The hydroxide
ion attacks the sulfur atom and kicks off this whole group, which will be the more important
fragment. Then, another hydroxide ion grabs this proton and we get this. And finally we can imagine
this nitrogen pushing its lone pair onto the other nitrogen to kick off this hydroxyl group,
and that gets us to the zwitterionic form of diazomethane, which is co-distilled in ether. This
is then titrated with a carboxylic acid and used directly rather than being stored, as diazomethane
is quite explosive, and this synthesis should only be attempted by trained chemists.
Once synthesized, this molecule has some interesting applications.
To start with something simple, this can be used to convert carboxylic acids into methyl esters,
in case a more typical method like acid catalysis is undesirable for one reason or another.
This method is quite straightforward. Considering this resonance structure of diazomethane, we can
see that the carbanion will be protonated by the carboxylic acid. That gives us a diazonium cation,
which is extremely unstable, such that even a carboxylate anion is capable of performing SN2,
attacking the carbon atom, and kicking off molecular nitrogen. The carboxylate has been
methylated, leaving us with the methyl ester. This technique can be extended to phenols as well,
which can be methylated by the same method, since phenols are relatively acidic
due to the resonance stabilization of the conjugate base. Normal alcohols, however,
are not acidic enough to protonate diazomethane, and thus will not work for this type of chemistry.
Alcohols can be methylated in this way if the mixture is irradiated with light
of a particular wavelength, but again, we will investigate photochemistry later in the series.
Another important application of diazomethane is the homologation of carboxylic acids by one
carbon atom. What this means is that diazomethane can insert a carbon between the carboxyl carbon
and the adjacent carbon, to make the carbon chain one longer. This amazing reaction was discovered
by two German chemists in 1935, Fritz Arndt and Bernd Eistert, hence it is called Arndt-Eistert
homologation. The way this works is as follows. Because one of the resonance structures for
diazomethane bears a formal negative charge on the carbon, the composite will still bear
a partial negative charge at this location, and thus this carbon is somewhat nucleophilic.
Carboxylic acids can be primed for nucleophilic attack by conversion into the acid chloride,
so we will first do this with SOCl2, and then react with diazomethane,
which will attack the carbonyl and displace the chlorine. This is done with triethylamine to act
as a proton sponge, which will accept one of the protons that was on diazomethane,
leaving us with this alpha diazoketone. Heating this will prompt the loss of nitrogen gas,
and will leave us with a carbene, just as we are familiar with. We can call this an acyl carbene.
Carbenes are unstable, as we know, and so there is some impetus for this structure to rearrange
if possible, so as to give each carbon an octet. This is indeed possible here, if the lone pair
coordinates to the adjacent carbon to produce a double bond, with the R group then shifting
over and coordinating to this carbon. This particular 1,2-shift is also known as the Wolff
rearrangement, and it leaves us with something called a ketene, which although unstable, is a
much more stable structure than a carbene, given that both carbons have an octet. Then hydrolysis
will occur, where nucleophilic attack from water will bring us back to the carboxylic acid,
and there we have our product, a carboxylic acid with one more carbon than we started with.
The interesting thing about this reaction is that once homologation is complete,
it can be repeated as many times as necessary to produce a carboxylic acid of any chain length.
This makes it quite a valuable addition to our arsenal of synthetic techniques.