(Hive Addict)
02-21-04 22:13
No 490200
(Rated as: excellent)
Selective reactions between phenols and formaldehyde. A superior synthesis of salicyl alcohols.
Giovanni Casiraghi, Giuseppe Casnati, Giuseppe Puglia, Giovanni Sartori
Synthesis (1980), 02, p. 124
No DOI number found
Full text: http://www.geocities.com/phorkys_hecate/
The phenol-formaldehyde reactions occupy a relevant position among industrial processes as the reaction products are important and widely used commercial chemicals. Although general base and acid catalysis, as well as directive catalysis, in both aqueous and non-aqueous systems recieved a great amount of study, only scant attention was given to uncatalysed reactions.
The work reported herein affords a practical, efficient route to salicyl alcohols via uncatalyzed C-ortho site specific monohydroxymethylation of phenols with formaldehyde. Treatment of the phenol 1 in xylene with an excess of paraformaldehyde (2; 10 mol equiv) in the presence of 1 mol equiv of an ether additive such as dimethoxyethane afforded the salicyl alcohols (3a-q) in high yields and excellent selectivity. The table lists the starting phenols 1 and yields of salicyl alcohols 3 produced.
This new method appears to be general for phenols with alkyl, cycloalkyl, aryl, alkoxy, and hydroxy substituents present in the structure. In contrast, phenols bearing strongly electron-withdrawing substituents are inert under these reaction conditions.
The present process provides an extremely simple method for the synthesis of a variety of ortho-hydroxybenzyl alcohols. In this process both yields and selectivity are high with 70-96% conversion. The work up requires only separation by destillation and/or crystallization after which unreacted starting compounds and the solvent system can be recycled.
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3n - p-methoxyphenol - m-methoxysalicyl alcohol - 66% yield
3o - hydroquinone - 2,5-dihydroxybenzyl alcohol - 59% yield
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The most used methods for the C-ortho site selective synthesis of salicyl alcohols are based on reaction between boron phenoxides and formaldehyde (or their derivatives) in non-polar aprotic solvents. Alternatively, good results can be obtained using ortho-directive catalysts such as divalent metal ions in non-aqueous media. To our knowledge, no method that avoids the use of a catalyst has been reported. The present process provides one of the most efficient methods for the mono ortho-hydroxymethylation of phenols. The convenience and high yields as well as the lack of complicated manipulations suggest that this procedure can be an economically viable route for both large and lab-scale production of salicyl alcohols.
General procedure
The appropriate phenol 1 (1.0 mol), paraformaldehyde (2; 300 g, 10.0 mol), xylene (600 ml), and dimethoxyethane (90 g, 1.0 mol) are mixed in a closed reactor equipped with a mechanical stirrer and a thermocouple. The reaction mixture is stirred vigorously for 12 h at 135°C, then cooled, the insoluble unreacted paraformaldehyde is filtered and washed with xylene. The filtrate is evaporated to dryness in vacuo to leave the crude product 3 which is purified as follows:
compounds 3a, 3b, 3g and 3n by high vacuum distillation and subsequent recrystallization from benzene/hexane (1:1 v/v mixture); compounds 3c, 3d, 3f, 3i, 3j, 3k, 3l, 3m and 3p by recrystallization from ligroin; compounds 3e, 3n and 3q by recrystallization from benzene. The purity of the products was determined by gas-liquid chromatography (SE-30) and found to be >98% pure. Yields and physical data for all alcohols 3a-q are collected in the table.
Preparative-scale reactions listed in the Table were carried out in a 1000 ml stainless steel autoclave.
Bp. of dimethoxyethane (monoglyme) is 84-86°C. Maybe one could exchange this for diglyme, with its bp. of 162°C the reaction could perhaps be performed at atmospheric pressure?
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(Hive Addict)
02-21-04 22:51
No 490207
Haha, seems as if you suffered from the same repeated entry disruption I encountered in the chemicals/equipmetn forum.
What exactly is m-methoxysalicyl alcohol (synonyms/chemical names)? And what can it be converted to?
(Hive Addict)
02-21-04 22:59
No 490210
I got the screen 'internal server error' every time.
I deleted the other unnecessary ones.
What exactly is m-methoxysalicyl alcohol (synonyms/chemical names)?
m = meta
salicyl alcohol = 2-OH-benzyl alcohol
so m-methoxysalicyl alcohol = 2-OH-5-MeO-benzyl alcohol,
methylate this and you have 2,5-DiMeO-benzyl alcohol.
Brain fart edited
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(Hive Addict)
02-21-04 23:26
No 490213
For some reason I was thing ortho was 2 and meta was five para 4
Thanks!! Awesome post!
Edit: Oh shit, I need some more sleep! meta-methoxy not meta salicyl, duh... 5-methoxy.. Nevermind.
(Hive Addict)
02-21-04 23:35
No 490216
ortho = 2
meta = 3
para = 4
In this case, ortho is the free position next to the -CH2OH, next place is meta, next one is para; draw them both and you'll see.
If this reaction can be run at atmospheric pressure, which I suspect will work if a high boiling ether like diglyme is used, it is an almost OTC way. If you have the 2,5-dimethoxybenzyl alcohol, you can proceed to the benzyl chloride, and from this to the nitrile with KCN or to the benzaldehyde with the Sommelet (hexamine).
What I find strange is that they didn't specify how they isolated 2,5-dihydroxybenzyl alcohol.
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