flyingbanana
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Controlling Monomethylation of Hydroquinone to p-methoxyphenol
There are references on monomethylation of hydroquinone with benzoquinone, MeOH, and H2SO4, but is there any way technique-wise to accomplish the same
thing using traditional methods?
I was picturing a 3-neck flask with reflux condensor and 2 addition funnels, one with alkali and the other with a less strong methylating agent such
as trimethyl phosphate. If you were to control the addition of both alkali and TMP, is monomethylation in decent yield possible?
I was also wondering if this route is also feasible to p-methoxyphenol: anisole -> p-bromoanisole -> p-hydroxyanisole. Basically, would that
dehalogenation step work (reaction with NaOH and copper catalyst)? I thought Halogen substitution on aromatics is only efficient with some electron
withdrawing group like aldehyde. If this method is possible, then it would be a much cleaner way to p-methoxyphenol.
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sparkgap
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Monomethylation of diphenols like hydroquinone is more of a "statistical" matter. You're basically talking about two -OH groups
reacting equally likely with whatever methylating agent you care to employ. So, you may get some methoxyphenol. As to a decent yield, I cannot
comment.
Methinks better luck may be had by doing a Sandmeyer on anisidine:
p-CH<sub>3</sub>OC<sub>6</sub>H<sub>4</sub>NH<sub>2</sub> + NaNO<sub>2</sub>
--H<sup>+</sup>--> (diazonium salt) --OH<sup>-</sup>--> p-methoxyphenol
Remember to do this in the cold.
sparky (^_^)
P.S. Alkylating benzoquinone instead of hydroquinone, however, I have no idea how such would proceed. 
[Edited on 6-3-2005 by sparkgap]
"What's UTFSE? I keep hearing about it, but I can't be arsed to search for the answer..."
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Eclectic
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I've Googled "methoxypenol benzoquinone" and did not see an obvious prep in the first few pages. Could someone post the prep of
p-methoxyphenol using benzoquinone, MeOH, and H2SO4?
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alchemie
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Eclectic:
here it is.
sparkgap:
The sandmeyer should work, but yields for the transformation of the diazonium to a phenol are generally small.
Quinones can be alkylated with alcohols and a reducing agent to form alkoxy phenols. e.g. this
flying banana:
Methylations using trimethyl phosphate don't really qualify as "traditional means".
What's wrong with MeOH, H2SO4 and benzoquinone? If you can get the hydroquinone the benzoquinone can be synthetized from that (there's a
shitload of methods) and all the rest is easily found OTC.
Bromination of anisole should give you a mixture of ortho and para. You would have to separate these, or dehalogenate and separate the phenols. As to
the dehalogenation I have no idea.
[Edited on 7-3-2005 by alchemie]
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enima
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Anisole can be selectively brominated using oxone & NaBr, H2O2 & Amm. Bromide, NBS. these methods provide for high regioselectivity of the
para position for bromination of anisole.
If you would like the actual papers I could provide those.
keep in mind yes u need an electon withdrawing group in the correct position for the swap to occur. (br---> oh)
[Edited on 7-3-2005 by enima]
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Sandmeyer
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The alcohol/H2SO4 monomethylation of HQ has been tried by Antoncho and seems messy. p-methoxyphenol is of course cheap and as available as HQ so I
would presonally never make it. But p-ethoxyphenol is expensive and needs to be made, I have posted this before:
Monoacetyl hydroquinone
In the solution of 220 g(2 mol) of hydroquinone in 500 ml of acetic acid, 102 g(1 mol) of acetic anhydride was drop-added for one hour while agitating
the solution at 110[deg.] C. The mixture was maintained at 110[deg.] C. for two hours, and acetic acid was distilled under vacuum. 1 liter of toluene
was added to the reaction mixture and the unreacted excess hydroquinone was filtered and collected (recovered amount: 110 g, recycled without any
purification process). A desired monoacetyl hydroquinone was obtained by evaporating the residue under vacuum. (Yield: 149.1 g(98%). mp: 60-62[deg.]
Acetyl chloride can be used in place of acetic anhydride. Monoacetylation -> alkylation -> hydrolysis would provide the wanted cmpnd. The key
for monosubstitution is to not have any base present.
Another nice thing one could do in theory is monoacylate (w/ propionic/acetic acid anhydride/chloride), alkylate with the desired alkylhalide and
instead of simply hydrolysing the ester do a Fries rearrangement to get the propio/acetophenone directly, alkylate the other -OH on the ring and get
2,5-(unsymetric)-alkyloxy-propio/acetophenone, which can be turned into some fun compounds.
[Edited on 16-3-2005 by Sandmeyer]
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Nicodem
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OK, it is true that the monomethylation of hydroquinone yields a dirty product which needs to be vacuum distilled. I tried it and it is a simple,
cheap and high yielding reaction, but the product was dark and had a large melting point depression (even as much to refuse to fully crystallize at
room temperature). Since vacuum distillation was out of my reach in those days, I tried to recrystallize from water and water/EtOH but it wasn't
easy and anyway, it did not help much.
But this doesn't mean that p-EtO-phenol would also be that hard to purify. Since it is more soluble in toluene than p-MeO-phenol it might be
easier to wash out hydroquinone and other polar byproducts with brine. Then one could extract it from toluene with 10% NaOH, leaving behind all
non-phenolic byproducts and then precipitate p-EtO-phenol with concentrated HCl. I'm not sure if it would give a pure product, but it should be
pure enough for many reactions. For example if one for any weird reason would want to formylate it, then using either the HCHO/Mg(OMe)2 or HMTA/AcOH
method should work just fine even if the monoalkylhydroquinone is not pure. Later on, the products, like 2-OH-5-RO-benzaldehyde in such case should be
easily purified by recrystallization.
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Sandmeyer
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3 Duff formylations:
1.) 2,6-Diformyl-4-methoxyphenol
4-Methoxyphenol (5.243 g, 42.2 mmol) and hexamethelenetetramine (11.95 g, 55.1 mmol) were dissolved in anhydrous trifluroacetic acid (60 mL) under N2
and the mixture stirred for 24 h. The mixture was poured into 4 M HCl (200 mL) and stirred for 10 min, after which time it was extracted with CH2Cl2.
The combined organic extracts were washed with 4MHCl, water, and saturated brine, dried (Na2SO4), and evaporated to give a yellow crystalline residue.
The product was purified by column chromatography to remove baseline impurities and trace amounts of 5-methoxysalicylaldehyde. This gave
2,6-Diformyl-4-methoxyphenol as yellow needles: yield 2.4 g (32%)
Sharghi, Hashem; Nasseri, Mohammad Ali; Niknam, Khodabakhsh; J. Org. Chem.; 66; 22; 2001; 7287 - 7293.
2.) 3,5-dimethyl-4-hydroxybenzaldehyde
Thus, a mixture of 12.2 g of 2,6-xylenol (100 mmol), 14.0 g of hexamethylenetetramine (100 mmol), and 150 ml of trifluoroacetic acid was heated a t
reflux (83-90 C) for 12 hr. The products were concentrated and combined with 600 ml of ice water; the resultant mixture was stirred for 15 min, made
basic with Na2CO3, and extracted with ether. Evaporation of the ether solution left a yellow solid which was recrystallized from chloroform-pentane to
afford 14.3 g (95% yield) of 3,5-dimethyl-4-hydroxybenzaldehyde mp 111-112.5' (lit mp 113-114 C).
J. Org. Chem.; 1972; 37(24); 3972-3973.
3.) Syringaldehyde
http://www.orgsyn.org/orgsyn/prep.asp?prep=CV4P0866
J. M. Landesberg, L. Katz, and C. Olsen, "Organic Syntheses." Collect. Vol. IV , Wiley, New York, N. Y., 1963, p 866.
So, 1.) gives diformylation, maybe the use of acetic as you suggest and shorter reaction time would avoid overformylation?
2.) gives a great yield and could be used instead of 3.). I have requested a paper; Maillard,J. et al.; Bull. Soc.
Chim. Fr.; 1966; 2520-2524.
It is about 1,3,5-trihydroxybenzene --MeOH/H2SO4--> 3,5-dimethoxyphenol. On this compound method 2.) could be applied and maybe
tried with acetic instead of trifluoroactetic. If it gave good yield with acetic it would, IMO be the most OTC method for TMA-6.
[Edited on 17-3-2005 by Sandmeyer]
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Mephisto
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| Quote: | Originally posted by Sandmeyer
3.). I have requested a paper; Maillard,J. et al.; Bull. Soc. Chim. Fr.; 1966; 2520-2524.
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I've scanned it two days ago. Just wanted to read it before posting, but the French-classes seems to
be to long ago for fast reading. However, here's your copy:
Attachment: Bull. Soc. Chim. Fr. 1966.pdf (316kB)
This file has been downloaded 1459 times
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Vitus_Verdegast
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2-OH-5-MeO-benzaldehyde
| Quote: | | For example if one for any weird reason would want to formylate it, then using either the HCHO/Mg(OMe)2 or HMTA/AcOH method should work just fine even
if the monoalkylhydroquinone is not pure. |
Same thing for the Reimer-Tiemann formylation. 2-OH-5-MeO-benzaldehyde can be obtained in good purity by steam-distilling the goo obtained from
extraction of the post R-T reaction mixture.
| Quote: | | Later on, the products, like 2-OH-5-RO-benzaldehyde in such case should be easily purified by recrystallization. |
2-OH-5-MeO-benzaldehyde is a yellow oil with a delicious sweet nutty/plastic raincoat like smell  after steam-distillation.
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