Reimer-tiemann

[obituary]

again, obit is taking a shot at the impossibility of obit actually getting a new synth.  but here goes:

step 1:  1,2,3-trihydroxybenzene + HCCl3 -(OH^-)-> 2,3,4-trihydroxybenzaldehyde (a)

obit has no doubt that step works. simple Riemer-Tiemann

step 2:  A + DCM -(OH[/sup]-<sup>)-> 3,4-MD-2-OH-benzaldehyde (b)(or the 2,3-md-4-oh side product)

not so sure about that step, b/c of the side rxn will drasitcally lower yeilds.

step 3: B+ nitroethane -catalyst-> the hydroxynitropropene.(c)

pretty sure that this will work with decent yeild

step 4: C+ some hydride red. ag. --> the hydroxy-MD-amphetamine

first of all, is it possible. Second, it the product active.  third, where would the methylation of the OH go to give best yeilds?  after step 3 or 4?  after 3 might cause the attack on the Double bond and after 4 might methylate the N.  anyways, it's all just an idea- maybe something else useful could come of it.  (especially considering, this probably won't work the way obit wishes it would)</sup>

[jim]

How about this tiny modifaction.

Instead of 1,2,3 trihydroxybenzene, use dichlorobenzene and get 2, 4 dichlorobenzaldehyde...

dichlorobenzene is sold as moth balls just about everywhere in the world...

[Rhodium]

Obit: The reimer-tiemann often gives complex polymers as by-products and has low yields.

The hydroxy-amphetamine is inactive, so you need to methylate it first. I suggest you do all the alkylation steps as your first move.


Jim: The reimer-tiemann formylation only works on aromatic phenols, not deactivated halobenzenes.

[obituary]

are the side rxns like aldol condensation (thinks it's aldol-maybe it's the other one, can't remember the name-alpha hydrogens/no alpha hydrogens?)  ?    is there a way to minimize this rxn?   maybe using a weaker base than OH?

[Rhodium]

I believe that the side reactions are polymers from the benzene nucleus cross-linking with another benzene nucleus, just like the plastic bakelite frorms from phenol and formaldehyde.

[jim]

Turning dichlorobenzene into dihydrobenzene would be very easy.  Just add heat and NaOH.

Given the relative expense (Cheap as sin) of 1,4-dichlorobenzene, NaOH, acetone, and bleach, I think that this is an alternitive.

[obituary]

how are you going to swap the Cl and OH's ?  aromatic halogens don't like to come off that easily.

[jim]

Phenol is prepared from C6H5Cl and NaOH.

C6H5Cl  +  NaOH aq. (~15%) @ 300 C  -->  C6H5ONa 

Also there is:

C6H5Cl  +  H2O  (Cu/ silca gel)  -->  C6H5OH