Rhodium (Chief Bee)
12-12-02 10:05
No 388805
      What's the chemistry?  Bookmark   

Is this first reaction of general applicability? If so, then it is a new way to synthesize 2C-T-X precursors. The second reaction is a formylation I have never seen before...

Methyl (3,5-diisopropyl-4-hydroxy)benzenesulfonate (6).

To 2.90 g (16.2 mmol) of 2,6-diisopropylphenol (1) dimethyl sulfate (8 g, 63.4 mmol) was added dropwise maintaining the temperature at 20-30 C. The solution was refluxed under stirring for 1 h and, after cooling, was diluted with cold water. Stirring was continued overnight at room temperature, and then the organic phase was extracted with CHCl3 (20 mL) and dried (Na2SO4) and the solvent removed by rotary evaporation. The residue was purified by silica gel column chromatography [petroleum ether/ethyl acetate 8/2 (v/v) as eluent)] to give 2 g (45%yield) of 6: mp 68-70 C.

3,5-Diisopropyl-4-hydroxybenzaldehyde (7).

To a solution of 2,6-diisopropylphenol (1) (1.5 g, 8.4 mmol) in glacial acetic acid (80 mL) were added 40% formaldehyde (1.5 mL) and 30% NH4OH (1.12 mL). After 24 h on the steam bath, the solvent was evaporated under reduced pressure and the residue dissolved in CHCl3 (20 mL), washed with 5% NaHCO3, and dried (Na2SO4). Evaporation of the solvent gave a residue which was purified by silica gel column chromatography [petroleum ether/ethyl acetate 9/1 (v/v) as eluent)] to give 0.60 g (35%yield) of 7.

Ref: J. Med. Chem., 41 (11), 1846-1854 (1998)
(Official Hive Translator)
12-12-02 10:34
No 388814
      Well,...  Bookmark   

The 1st rxn does look weird - even more so since, if you notice, they don't mention any solvent and still say 'reflux for 1h' -  whilst DMS (if that should bee the only solvt employed) not only boils at ~190 C, but also decomposes on boiling.

So i'd suggest they missed some essential detail there.

Now tell me this. How come there is never a single mention of someone trying to reduce a sulfonate to a thiol? Is that too hard to do?

I mean, the same result that is achieved here in that example can bee easily had by simply sulfonating , say, p-diMeO-benzene w/sulfuric acid. No?

THAT could well bee a very interesting area for the bees to research. Sulfuric acid itself gets reduced to H2S w/, e.g. aluminium - unfortunately, can't say anything on sulfonates. So, you, the ones who can - please do!


P.S. Yes, the 2nd rxn is a simple Duff formylation, only HMTA which is conventionally used is made in situ (or rather HMTA itself is decomposed in situ in the 'usual' Duff formylations - is that right?) from HCHO and NH4OH.

BTW, this aqueous acetic Duff formylation gives a great yield on 2,6-ditertbutyl-phenol, see Patent US4009210.
(Chief Bee)
12-12-02 16:02
No 388939
      I went to look more closely, and it seems like ...  Bookmark   

I went to look more closely, and it seems like Ph-SO2-R is not easily reduced to Ph-S-R - LAH is needed. R-SO3H can be reduced by PPh3/I2.

Phenylsulfonyl chlorides (Ph-SO2-Cl) are pretty easy to reduce though, see the 2C-T-2 section in Pihkal, in there one is reduced with Zn/HCl. HI can also be used for the reduction, and I have posted in the past of other possible methods.