(Hive Bee)
03-19-03 14:06
No 419042
      Base-catalyzed hydroxymethylation in methanol
(Rated as: excellent)

JOC;1957;22;1435-8;Karasch & Joshi;Reactions of Hindered Phenols.  I, Reactions of 4,4'-Dihydroxy-3,5,3',5'-tetra-tert-butyl Diphenylmethane.

"The base-catalyzed condensation of formaldehyde with IV is here carefully examined and is shown to give two different products depending upon the alcohol used as solvent."

(IV = 2,6-di-tert-butylphenol)

"The formation of VI in methanol and not in other alcohols (ethanol, 2-propanol, t-butyl alcohol) may be attributed to the higher acidity of methanol."

(VI = 4-hydroxy-3,5-di-tert-butylbenzyl methyl ether)

"It should be emphasized that oxygen must be rigidly excluded in all the base-catalyzed reactions of IV, otherwise there is a rapid condensation of IV to 3,5,3',5'-tetra-tert-butyldiphenoquinone VII."


"4-hydroxy-3,5-di-tert-butylbenzyl methyl ether (VI).

2,6-di-tert-butylphenol (5.2 g), 36% formaldehyde (5 ml) and absolute methanol (50 ml) were dissolved in a three-necked flask and a solution of potassium hydroxide (2 g in 2 ml water) was added under an atmosphere of nitrogen.  The solution was refluxed for 30 minutes under a current of nitrogen. After cooling, the pale yellow crystalline product was collected (5.5 g, 82%) on a filter, and crystallized severeal times from methanol. Colorless plates were thus obtained which melted at 99.5°."

Okay, this is the methyl ether of the benzyl alcohol, dunno how stable that is or if it could be useful. Off hand, this etherification of the benzyl alcohol seems similar to the acylation mechanism in Patent US5315018

Still, the authors claim in the beginning of the article:

"It was claimed by Bamberger (2a) that, in the presence of alkali, I reacts with formaldehyde at room temperature to give II. Above 30 years later, this observation was disputed by Granger. The latter investigator claimed that, under a variety of experimental conditions, I condenses with formaldehyde to give exclusively III. The authors, howevever, found no difficulties in preparing II by the Bamberger procedure, nor in preparing III by the procedure of Auwers."

(I = 2,6-dimethylphenol
 II = 4-hydroxy-3,5-dimethylbenzyl alcohol
 III = 4,4'-dihydroxy-3,3,5,5'-tetramethyl diphenylmethane)

(2a): E. Bamberger, Ber., 36, 2036 (1903)

Does anyone have this Bamberger-article handy?
(Chief Bee)
03-25-03 03:32
No 421002
      Bamberger article  Bookmark   

Chem Ber 36, 2036 (1903) (../rhodium/djvu /bamberger.djvu)
(Hive Bee)
03-27-03 16:30
No 421727
      Thanks a lot. Great. Just to quote from the...  Bookmark   

Thanks a lot. Great.

Just to quote from the article:



Die (wohl durch Luftoxydation grünfärbte) Lösung von 3 g Xylenol (Schmp. 44-46°, statt 49°) in 25 ccm 5-procentiger Natronlauge wurde nach Zusatz von 1.6 ccm 40-procentiger Formaldehydlösung drei Tage im geschlossenen Gefäss sich selbst überlassen und dann - ohne Rücksicht aug einen geringen Bodensatz - mit Essigsäure angesäurert. Es fiel ein röthliches, sehr rasch krystallinisch erstarrendes Oel aus (Filtrat F). Die abgesaugten und mit Wasser gewaschenen Krystalle (2.5 g vom Schmp. 92-94°) verwandelten sich durch zweimalige Krystallisation aus siedendem Benzol im seideglänzende, flache, constant bei 104.5-105° (Bad 95°) schmelzende Nadeln, deren Indentität mit dem oben beschriebenen Oxydationsproduct des Mesitols durch directen Vergleich festgestellt wurde.


No mention of yields as far as I can grasp, in the article. There seems to be a lot of references to articles by Lederer and Manasse in articles on hydroxymethylation. Especially these two:

Manasse, Ber. 27, 2409- (1894)
Lederer, J. Prakt. Chem. 50, 223- (1894)

I'll try to get these, but I guess it seems from the Bamberger article that benzyl alcohols are the product of hydroxymethylation with formaldehyde in basic aqueous solution.
(Chief Bee)
03-28-03 18:54
No 422032
      Lederer & Manasse articles  Bookmark   

../rhodium/pdf /lederer.pdf
../rhodium/pdf /manasse.pdf
(Hive Bee)
03-30-03 16:32
No 422483
      Thanks again. Yes, very nice.  Bookmark   

Thanks again.

Yes, very nice. Benzyl alcohols via base-catalyzed condensation of phenols with with aqueous formaldehyde.

Carbonates, hydroxides and other bases all catalyze the reaction.

No yields as far as I can see, but I can't see why they should be any lower than the condensation in aqueous methanol.

Why is it again this method has not been used to any great extent, clandenstinely? With p-methoxyphenol or something, I mean.

Well, it would be really fun if it works with non-phenolic aromatics. When catalyzed by sulfuric acid, this seems to happen as stated in the patent mentioned in Post 416309 (bottleneck: "Hydroxymethylation of aromatic ethers", Novel Discourse) and also in the synthesis of the DDT-like insecticides.

Is there a particular reason why acids should work to catalyze condensation with all aromatics, but bases only with phenols?
(Chief Bee)
03-30-03 20:07
No 422536
      Only phenols can form phenoxides with bases,...  Bookmark   

Only phenols can form phenoxides with bases, while phenols and phenol ethers are protonated pretty much similarly by acids, I don't know how much difference that makes here though.