Methansaeuretier
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Methylation with dimethyl sulfite - which base is suitable?
Hello...
I like to methylate 4-ethoxyphenol and toluhydrochinon with dimethyl sulfite (not dimethyl sulphate!).
Which base is suitable for this reaction?
I have no K2CO3 at the time. Are there any alternates? What about KOH/NaOH, etc.? Or does KOH/NaOH saponify dimethyl sulfite fast?
Thx
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Nicodem
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What do you think, that we can read minds? Post the reference.
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Nicodem
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Thread Moved
21-8-2010 at 13:28 |
Methansaeuretier
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http://www.patentstorm.us/patents/4453004/description.html upsi...
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....
EXAMPLE 3
In an apparatus as in Example 1, 10.0 g (0.054 mol) of syringaldehyde and 5.00 g (0.036 mol) of potassium carbonate were heated to 100° C. and 8 ml
(0.094 mol) of dimethyl sulfite was added over a 5 minute period. The pasty mixture washeated to 100° C. for 3 hours then cooled to 25° C. and
quenched with 50 ml water. The mixture was extracted with 100 ml of methylene chloride. The extracts were washed with water and concentrated in vacuo
to get 4.2 g (54% based onrecovered syringaldehyde) of 3,4,5-trimethoxybenzaldehyde. |
Btw... they only use less than 1 eq base for the phenol... that may cause the low yield.
There are some more errors in the patent I think... the base isn't a catalyst... it will react to X2SO3 I think.
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In carrying out the invention, it is desirable to use a small amount of a base catalyst. The reaction proceeds without a catalyst but at a very
reduced reaction rate. Any base may be used that neutralizes acid such as an alkali metal oralkaline earth hydroxide, an amine, ammonia or trisodium
phosphate. However, the alkylation reaction does not require heavy excesses of a base nor does is require a strong base. A strong alkaline catalyst
may be used but less than a molar equivalent ofthe strong alkaline catalyst will be necessary. It is preferred to use a weak alkaline catalyst and a
preferred class of such catalysts are carbonate salts such as sodium, potassium, magnesium or calcium carbonate. The small amount of carbonaterequired
for the reaction under normal pressure is between 0 and 10 mole percent, based on the total moles of reactant phenolic compound, although larger
amounts are not deleterious. Amounts as small as 0.1 mole will sometimes be adequate. Since thereis no solvent, the alkylating agent cannot be taken
up by any other reactant and hydrolytic side reactions are avoided. This leads to considerably improved product quality. |
Also in alkylation with dimethyl sulfate other bases than K2CO3, for exmaple Na2CO3, are known to give only low yields. (No ref... sorry  ) and KOH/NaOH are also known to kill esters even without a solvent but alkylation
with dimethyl sulfate and NaOH in water at rt does work very nice (Ref: http://www.erowid.org/library/books_online/pihkal/pihkal023....). But dimethyl sulfite is very unstable in water (this makes it btw a safe
methylating agent; causes no cancer as far as I know) (Ref(German): http://assets.chemportals.merck.de/documents/sds/emd/deu/de/... ).
[Edited on 22-8-2010 by Methansaeuretier]
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Nicodem
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Quote: Originally posted by Methansaeuretier  |
http://www.patentstorm.us/patents/4453004/description.html upsi...
| Quote: |
....
EXAMPLE 3
In an apparatus as in Example 1, 10.0 g (0.054 mol) of syringaldehyde and 5.00 g (0.036 mol) of potassium carbonate were heated to 100° C. and 8 ml
(0.094 mol) of dimethyl sulfite was added over a 5 minute period. The pasty mixture washeated to 100° C. for 3 hours then cooled to 25° C. and
quenched with 50 ml water. The mixture was extracted with 100 ml of methylene chloride. The extracts were washed with water and concentrated in vacuo
to get 4.2 g (54% based onrecovered syringaldehyde) of 3,4,5-trimethoxybenzaldehyde. |
Btw... they only use less than 1 eq base for the phenol... that may cause the low yield.
There are some more errors in the patent I think... the base isn't a catalyst... it will react to X2SO3 I think. |
Alkali hydroxides are probably not equally efficient in such a procedure instead of K2CO3. Though, possibly at least KOH might work more or less
efficiently if used only in ~10 mol% amounts, but higher amounts would be detrimental. I would not waste time trying with NaOH though. But I think you
can optimistically try with K3PO4 if you have any.
For example, these patent claims are typical cover all patent claims and trust me when I tell you that what is not in the patent examples was never
tried (sometimes even examples were not!):
"Any base may be used that neutralizes acid such as an alkali metal or alkaline earth hydroxide, an amine, ammonia or trisodium phosphate."...
"It is preferred to use a weak alkaline catalyst and a preferred class of such catalysts are carbonate salts such as sodium, potassium, magnesium or
calcium carbonate."
Hydroxides, amines and ammonia are too nucleophilic and will compete with the phenoxide and once methylated get deactivated (to quaternary ammonium,
water, etc.). Sodium salts, besides being less soluble, also generally form tight ion pairs in non-enough-polar and non-enough-protic reaction media,
so that they are to be avoided as they give lower conversions in such reactions, or none at all. MgCO3 and CaCO3 would be probably inert at the
reaction conditions as phenols would hardly react with them at only 100°C.
The use of less than one equivalent of K2CO3 does not appear that unusual if you consider that the basicity of potassium methylsulfite is
considerable, if not even comparable to that of carbonates. Thus the initially formed potassium methylsulfite should be able to deprotonate phenols at
least somewhat:
PhOH + MeOSOO<sup>-</sup> <=> PhO<sup>-</sup> + MeOH + SO2
Since MeOH and SO2 can leave the reaction mixture as gasses, the reaction is pushed forward even though the base might not be strong enough to
deprotonate phenols as efficiently as hydroxides or carbonates, for example. Thus, I would tend to believe the conversion could be increased, even up
to useful yields, by using an efficient distillation column and keeping the reflux at such a rate that only methanol distils out on the top of the
column. This is a bit of a problematic setup when working on few mmol reaction scale, but on larger scale it would be easy to perform. Try it on some
cheap phenol first.
The methylation of phenols with dimethyl sulfate in aqueous NaOH (as typicaly described in Organikum and other lab manuals) indeed works very well on
all kind of phenolic substrates, but it is a different type of reaction when compared to what we have here with dimethyl sulfite. Actually, NaOH and
KOH give equal result there exactly because it is an aqueous reaction. On the other hand, this methylation with (MeO)2SO is much more alike to the
methylation with dimethyl carbonate which also relies on the same catalytic base cycle:
PhOH + MeOCOO<sup>-</sup> <=> PhO<sup>-</sup> + MeOH + CO2
PS: All this is based on the presumption the patent examples are not just a bunch of bullshit!
…there is a human touch of the cultist “believer” in every theorist that he must struggle against as being
unworthy of the scientist. Some of the greatest men of science have publicly repudiated a theory which earlier they hotly defended. In this lies their
scientific temper, not in the scientific defense of the theory. - Weston La Barre (Ghost Dance, 1972)
Read the The ScienceMadness Guidelines!
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zed
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Use the base that the authors claimed to use. If you don't have any, buy or make some.
Syringaldehyde isn't easy to come by. Do what has the best chance of working.
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