Metacelsus
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Methylation of 1-iodo-2-naphthol
For a project I'm working on, I need to prepare 1-iodo-2-methoxynaphthalene. I have already iodinated 2-naphthol at the 1-position (using
NaI/H2O2 in acidic methanol). Now, I need to methylate the hydroxyl group. Most procedures I've seen (on Reaxys) for methylation
of a naphthol use potassium t-butoxide to deprotonate, followed by treatment with dimethyl sulfate. All the procedures that don't use dimethyl sulfate
use elevated pressure and temperature.
I can obtain and use potassium t-butoxide and dimethyl sulfate, but I'd rather not have to. Is there any nice way to perform the methylation with
milder reactants?
[Edited on 6-26-2016 by Metacelsus]
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myristicinaldehyde
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Now, I am no expert, but I always assumed ch3i would make a phenol into a methoxy group. Why wouldn't it work here?
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Crowfjord
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KOH and methyl bromide work quite well for various phenols. Methyl iodide would of course also work, and be easier to handle. The reaction proceeds
fastest in polar aprotic solvents like DMF or DMSO. I've also used methanol and ethanol, relying on the low solubility of potassium bromide to help
drive the reaction.
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Pumukli
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We used dimethylsulfate + aqueous solution of NaOH when made neroline (2-methoxy-naphtalene). The yield was not bad.
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UC235
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I've sucessfully made 2-methoxynaphthalene using EtBr and NaOMe as the base in methanol solvent. It's quite slow (18hr reflux, IIRC). MeI should be
much faster, maybe 2-4hr.
Also, unmethylated starting material can be easily removed by strong alkali washes
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Metacelsus
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How would you get 2-methoxynaphthalene from ethyl bromide? Are you sure you didn't mean ethoxy? Anyway, thanks for the tip about
workup. Whatever procedure I use, I'll post the results.
[Edited on 6-27-2016 by Metacelsus]
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UC235
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Right, ethoxy. Long day.
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Mesa
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https://www.erowid.org/archive/rhodium/chemistry/oxone.aroma...
Seemingly accidentally done here in 1 pot with 49% yield from naphthalene(KI + oxone + MeOH)
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Metacelsus
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No, that procedure on Erowid started with 2-methoxynaphthalene (entry 9 on the table).
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kavu
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A quick reaxys search finds only two literature examples for methylating 1-iodo-2-naphthol, whereas iodinating 2-methoxynapthalene gives 46 hits. With
the methoxy in place, the aromatic system is still electron rich enough to be iodinated in good yields. In this case the order of functionalization
does not make any strategic difference, so reversing the order might be a good idea. A straight forward procedure calls for 1 mmol of substrate in 4
ml acetonitrile + 1.1 equiv. NIS + 0.3 equiv. trifluoroacetic acid (86% yield from 2-methoxynaphtalene, 10.1016/S0040-4039(02)01010-9)
They also note that "reaction of 2-methylnaphtalene (entry 9), meta-xylene (entry 8) and diphenylether (entry 10) required refluxing acetonitrile to
be completed in 2.5–6 h."
[Edited on 28-6-2016 by kavu]
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Metacelsus
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Methylation of 1-iodo-2-naphthol
1-iodo-2-naphthol (9.4562 g, 35.014 mmol) was dissolved in acetone (35 mL). Finely ground anhydrous potassium carbonate (9.6853 g, 70.079 mmol) was
added, and the suspension stirred for 20 minutes. Dimethyl sulfate (5.00 mL, 6.67 g, 52.8 mmol) was added dropwise over 5 minutes. The reaction was
monitored by TLC; all starting material was consumed after 2.5 hours. Ammonia (14.8 M in water, 7.00 mL, 104 mmol) was added slowly over 5 minutes.
Then, water (25 mL) and ethyl acetate (35 mL) were added. The aqueous layer was removed, and washed with an additional 5 mL ethyl acetate. The organic
layers were combined, washed with brine (10 mL), and dried (MgSO4). The solvent was evaporated to yield the product as a tan powder (8.4433 g, 29.722
mmol, 84.8%).
TLC (4:1 hexanes/ethyl acetate): Rf 0.45
Melting point: 82.5-87.6 C (lit. 88.5-89 C, when recrystallized from methanol)
Comments: I was expecting a yield of >90%, especially because I used excess dimethyl sulfate. The lower yield might have been due to my starting
material still having solvent in it. The product's melting point is a bit low, and could probably be improved by recrystallization.
Kavu: I thought about making 2-methoxynaphthalene, and then iodinating it, but I had the materials for the iodination before I had them for the
methylation. For the iodination, I used 60 mmol 2-naphthol, 60 mmol NaI, 90 mmol conc. sulfuric acid, and 120 mmol hydrogen peroxide, all in 300 mL
methanol. The reaction took 3.5 hours, the first 2 of which were in an ice bath (the remaining time was at room temperature of 21 C). Yield was 97.4%,
but I think the product (a waxy solid) still had some ethyl acetate in it from the workup. It was pure by TLC (4:1 hexanes/ethyl acetate Rf 0.23), but
I didn't check melting point.
[Edited on 6-29-2016 by Metacelsus]
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Crowfjord
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Nice, Metacelsus. Alkylations in acetone with potassium carbonate can be tricky; they usually don't work unless conditions are completely anhydrous.
Did you take any special care to dry the acetone?
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Metacelsus
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The acetone was distilled, and then kept in a tightly sealed container, so I don't think it had much water in it. However, I didn't use any drying
agents to dry it.
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