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I have the following question for homework and am stumped. I am tasked with separating 3-(2-methoxyphenoxy)propane-1,2-diol and (1​R,2​S)-2-(methylamino)-1-phenylpropan-1-ol. They are both solvated in water.

compounds

I was thinking to work up with acid to cleave the ethers on the left compound, but that won't do much to reduce solubility for crystallization. Esterification with a large hydrophobic carboxylic acid wouldn't do much either because both compounds have hydroxyls. Anyone have suggestions?

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  • $\begingroup$ If you don't want to protect the diol, maybe reversed-phase chromatography could do the trick. $\endgroup$ – Autumn Feb 9 '17 at 7:46
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I am tasked with separating these two compounds.

If you want to keep both compounds, degrading one of them is obviously not an option.

They are both solvated in water.

This can be changed - reversibly ;-)

Your left compound is a diol. React the mixture with a ketone in the presence of an acidic catalyst.

Typically, these reactions are performed to protect ketones by heating them in with ethanediol in toluene in the presence of toluene sulfonic acid. There is no reason not to use it the other way around to protect the diol.

The reaction product is a cyclic acetal (1,3-dioxolane) which is much less soluble in water that the parent diol.

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    $\begingroup$ I think you could also protect the amine using a similar strategy (with different reagents of course). $\endgroup$ – Curt F. Feb 9 '17 at 5:38
  • $\begingroup$ Yeap but more difficult I think, considering that you also have an alcool function that may react and the stereochemistry to keep. $\endgroup$ – Autumn Feb 9 '17 at 7:47
  • $\begingroup$ @Autumn Epimerization of the OH in the amino alcohol during deprotection was my concern too. $\endgroup$ – Klaus-Dieter Warzecha Feb 9 '17 at 8:05
  • $\begingroup$ Actually, I remember the odd total synthesis (read: Trauner Denksport) that used an acetonide to protect a 1,2-diol. Or a benzaldehyde-acetal to protect a 1,3-diol. So it’s not entirely uncommon. $\endgroup$ – Jan Feb 9 '17 at 12:57
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Neutralize the amine with HCl to pH 4-5 to make it even more hydrophilic. Then add lots of NaCl to salt out the diol. Separate the diol and then basify the amine solution to salt it out.

After neutralizing (and again after adding salt and decanting the diol), cooling the aqueous solution might precipitate the amine hydrochloride as a crystalline material. So if the diol doesn't salt out, maybe the amine hydrochloride will.

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