This is another of the procedures presented to HyperLab by Zealot, a highly remarkable individual, who has just recently joined our small community.
There are more to the procedures he submitted, but i'll omit some of the theory, if any questions should arise - ask.
Alkylations of phenols with diazomethane is a carbene reaction - where the reacting species is :CR
2 - another well-known of this kind is Reimer-Tiemann formylation, where the active particle is :CCl2.
The unique property of diazomethane methylations is that, in case of polyhydric phenols, methylation occurs at only one -OH of the ring, until virtually all of the starting reagent is monomethylated; only then the second hydroxyl starts being methylated, and, in case of three hydroxies, this rxn also selectively proceeds until full dimethylation occurs, etc.
Thus, taking a calculated qtty of reagents, it is possible to stop the rxn at any of the stages, obtaining a good yield of, say, p-MeO-phenol or diMeO-phloroglucinol, which can bee then subjected to Reimer-Tiemann or Duff formylation.
Decomposition of diazomethane, required to form :CH2 radical, is catalyzed by Cu species - copper powder, Cu2+ or Cu+ unhydrous salts (sulfate, stearate, halides, complexes w/phosphoric acid), where Cu powder is the least reactive, Cu+ the most and CuSO4 is of intermediate activity.
Contrary to the accepted opinion, diazomethane is not so much poisonous and dangerous. The main thing to keep in mind is that one shouldn't heat concentrated solutions of DM by adding large qtties of it to the rxn , and not to add too much of decomposition catalyst (copper salt).
Tranferring diazomethane solutions is still better to carry out in a gas mask or in a glovebox
The following is a practically confirmed - and optimized - writeup (Zealot also stated the original printed procedure, but there's really no need to quote it)
Preparation of diazomethane1. Nitrosylurea.100 g (1,5 mole) methylamine*HCl and 300 g (5mole) tech grade urea is dissolved in 400ml tap water and the mixtr is heated w/a reflux condenser for 3 hrs at steady boiling. Then into the hotmixtr is added 110 g NaNO2 - the soln turns slightly yellow and a weak ammoniac smell appears. It's then cooled to 0 C and with good stirring there is added a thoroughly chilled mixtr of 110 g conc. H2SO4 and 600 g ice or snow. Nitrosylurea floats as a white foamy crystalline precipitate.
Yield 110-122 g (66-72%)
It is used immediately (it can bee washed, filtered and dried - but that's highly undesirable, since it's unstable and decomposes slowly at temps above zero - at 20 C it decomposes instantly, but w/out an explosion - however, emitting poisonous and stinky methylisocyanate)
2. Diazomethane.Into a FBF there is poured 100ml hexane (or any other water-immiscible unreactive liquid - benzene, ether), 40 ml 40% KOH or NaOH, all is chlilled to 5 C, then w/constant cooling and shaking, 10 g nitrosylurea is added 9
(Zealot: "...i always worked w/amounts 2-3 times more than") over the course of 1-2 mins (longer addition time doesn't affect the yield). Dark-yellow hexane layer is easily decanted, it contains 2,8 g diazomethane, some impurities and water. water can bee removed by drying it w/KOH (don't use KOH as sharp sticks - sharp edges facilitate DM's decomposition), however, for methylations water needs not bee removed.
Examples.1. Preparation of p-MeO-phenol.To asoln of 14,7g hydroquinone in 100 ml benzene there's added 0,05 g unhydrous CuSO4 and w/intensive stirring and RT there's added gradually 7 g DM in 150 ml benzene over 1 hour. When all dM is added, the rxn is stirred for 30 mins at RT and 30 mins at ~50 C.
Then the rxn is washed w/50% NaOH aq., until the washes remain completely colorless. Benzene is distilled off, giving an insignificant qtty of p-DMB. The aq. washes are neutralized HCl untill wekly acidic, xtract w/ether or C6H6 and evaporate to obtain ~15 g p-MeO-phenol as slightly brownish crystals.
2. Preparation of p-diMeO-benzene.To a soln of 9 g HQ in 100 ml benzene there's added 0,05 g unhydrous CuSO4 and over an hour, w/intensive stirring and RT, there's gradually poured in 8 g DM in 150 ml benzene. When all is added, the rxn is stirred for 30 min at RT and 30 min at ~50C.
Then into the rxn, without cooling it, there's added in drops a small qtty of HCOOH, until doesn't lead to emission of gas (N2). The mixtr is washed w/2*30 ml water to remove residual CuSO4 and HCOOH,dried w/MgSO4 and the solvt removed on waterbath. Yield almost quantitive - ~11 g.
Antoncho
P.S. I am certain that this is not the only way to use diazomethane (although the only another i can remember at the moment is chloroacetone synth ). If anybee has any ideas about this most interesting chemical, please, post them here!