This is a product of strictly retrosynthetic thinking and analysis.
I haven't been around lataly due to the fact that I was burried in litterature, studying to my exam, actually while doing that I got some nice ideas. Earlier I posted in a big hurry some errorous mechanism and that was foolish. Of course I havent tested this synth, I don't posses any lab, and i say no to drugs, but I have however double checked every step, and no rules are violated, but I guess you never know how it looks in practice unless you try it out. This one seriously looks promising since methods applyed are generall and well-known... Lilienthal, please comment if you find something unexpected
Step from pre-cursor [1] to [2], is in my opinion most critical step why? We've got a strong activaing ortho-para director in form of a -NH2 (amino) group on p-amino-toluene, incoming nitro (-NO2) groups cannot however be attacked by the para position, that's a positive thing, this inability is due to the occupied para position by (-CH3). What is even more interesting is that we can in this particular synthesis optimally take advantage of the -NH2 group (ortho-para director). In most cases this group needs to be manipulated/treated with Cl-(C=O)-CH3 (acylchloride, acetylated) in order to make it less activating and thereby give it any synthetic value, becose often we don't want to put things on BOTH ortho positions, in this case we want to do just that, and that will most likelty result in quantitave (100%) yeild of the product desired. In this step the NO2 ions are produced "in situ" by H2SO4 dehydrating The HNO3 (-H2O) => NO2.
Warning! 0-5 C should be strictly obeyed becose we are dealing with potentiall explozive [4]. The step from pre-cursor [3] - [4] is where HONO (nitrous acid) is generated "in situ" as well, by reacting HCl (HX) with NaNo2. I didn't show that in the diagram, I wanted to keep it as brief as possible, but the salt formed [4] is actually X(-) N2(+) or if HX used to generate HONO is HCl, Cl(-) N2(+), treating this salt with Cu2O, Cu (2+), H2O, upon gentle heating will generate the best possible leaving group (nitrogen gas), forget triflate, this guy is as inert as a group can get and you don't have to show him the door, he'll allow him self out
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Pre-cursor [5] is formed. Since phenols are quite acidic, stealing the hydrogen from their OH isn't that hard, we can modify Williamson ether synthesis and use NaOH instead of elemental Na as with alkane alcohols. This is one more benefit among many in this synthesis.
Going from [6] to [7] is simple introduction of Me groups to form ether, a la Williamson.
About time to treat [7] with NBS, [8] is formed followed by a simple Sn2 mechanism where cyanide ion (:CN -) (love it, hate it, FEAR IT) kicks out Br, and couples to form corresponding nitrile [9], this is treated with Raney Ni or LAH to convert the poision to the most divine psychedelic around => M [10].
It's amazing how organic chemistry and inorganic chemistry come together in this synth
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As complementary synthesis to the one above is the preparation of CN(-) needed for the nucleophilic substitution (nitrile production). Synthesis I came up with would if it worked actually give HCN a deadly gaseus poision, nothing a sensible man wants to mess with. However it could be possible to convert this gas into the CN(-) in situ by treatment with strong base, maybe NaOH in order to strip off the hydrogen and make an anion, prefrably giving NaCN. Preform the reaction at the last step in alkaline solution.
H-CN + NaOH (aq) -> Na(+) :CN(-) + H2O
I'm not familiar with the pKa of H-CN, you should look it up if you are considering to preform my HCN synth.
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Comment: Oxidation of MeOH with KMnO4 will give formic acid, corresponding acyl chloride by treatment with SOCL2, whereupon treatment with amonia will give formamide, when this material is refluxed with aceticanhydride HCN is evolved, please don't preform this if you are not a trained chemist. Even Death comes in 3 different forms, solid, liquid and gaseous, HCN is gaseous form of Death wich you can't escape from, it will creep up the condenser, hunt you down and kill you. When it's finally satisfied it will creap back to hell where it came from along with your soul. You have to posses certain skills and techniques in order to defeat this demon from the ancient world. Noone knows what HCN smells like, the one who get to know it dies, so don't think "well i'll notice it coming out, it has to have a charasteristic smell". Yeah, the one of death. Please don't fuck with this one, please...
[pH]armacist - Never underestimate the power of retrosynthesis. 1-800-MANTLE-NO-TNX