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I am attempting a synthesis for acetylacetone. The preparation I wish to carry out is described on orgsynth by condensation of acetone and ethyl acetate with a base catalyst.

The problem for me is that I only have $\ce{t-BuOK}$, no THF and $\ce{t-BuOH}$ in sight, only $\ce{EtOH}$. First I searched for solubility of $\ce{t-BuOK}$ in ethanol, only to find nothing. It gave me some ideas why there is no data for the solubility so I assumed already that they react (Why didn't I think of this in the first place). I instantly looked up for this procedure but I could not find anything satisfactory for this specific reaction, only patents about metathesis reactions of alkoxides with higher carbon chain alcohols. On the Wikipedia site there is a line of information that was somewhat useful, which states that "many alkoxides are prepared by salt metathesis from sodium ethoxide", but still not satisfactory since its the reverse what I am looking for.

The $\mathrm{p}K_\mathrm{a}$ of $\ce{EtOH}$ is 15.9 while $\mathrm{p}K_\mathrm{a}$ of $\ce{t-BuOH}$ is 16.5 in water. Looking at the values in DMSO the value of $\ce{EtOH}$ is still lower, so perhaps it can be generally stated the ethanol molecule has more tendency to deprotonate. Assuming and without cited literature by using excess $\ce{EtOH}$ (and as a solvent of course) I am expecting them to produce $\ce{EtOK}$ and $\ce{t-BuOH}$ by equilibration the mixture. I think that which base I use does not really matter in the reaction, but I'm short of solvents for solving $\ce{t-BuOK}$ efficiently and a little tertiary alcohol wont mess up my experiment. I am very confident about this simple metathesis reaction, but I would like to hear your ideas too before doing anything.

So my question, in short is the following: Will $\ce{t-BuOK}$ react with $\ce{EtOH}$ to produce $\ce{EtOK}$ and $\ce{t-BuOH}$?

I am of course aware of the dangers of these compounds, and have a basic experience in doing simple preparations like these.

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  • $\begingroup$ The key question here is whether you can do the condensation using t-butoxide in EtOH and in my opinion you can. Whether the functional base is t-butoxide or ethoxide is immaterial, it will do the reaction. $\endgroup$ – Waylander Jul 17 '20 at 6:44
  • $\begingroup$ It is my intuition too, but that is another topic my question is not about the condensation. $\endgroup$ – Andrew Kovács Jul 17 '20 at 8:11
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The answer is yes, it will be in following equilibrium:

$$\ce{EtOH + t-BuO- <=>[$K$] EtO- + t-BuOH}$$

$$K = \frac{[\ce{EtO-}][\ce{t-BuOH}]}{[\ce{EtOH}][\ce{t-BuO-}]} = \frac{[\ce{EtO-}][\ce{H3O+}]}{[\ce{EtOH}]} \times \frac{[\ce{t-BuOH}]}{[\ce{t-BuO-}][\ce{H3O+}]} = \frac{K_\mathrm{a}(\ce{EtOH})}{K_\mathrm{a}(\ce{t-BuOH})} \\ = \frac{1.26 \times 10^{-16}}{3.16 \times 10^{-17}} \approx 4$$


Edit:

Although the individual $\mathrm{p}K_\mathrm{a}$ values used to determine the $K$ in this equilibrium are calculated for solutions in water (some of those are only available in DMSO other than water), I assumed the ratio might be closer to the real value. However, an empirical conversion method that transforms $\mathrm{p}K_\mathrm{a}$ values of arbitrary organic compounds from one solvent to the other is introduced in this reference (Ref.1). Unfortunately, the full paper is behind paywall, but its abstract states that:

An empirical conversion method (ECM) that transforms $\mathrm{p}K_\mathrm{a}$ values of arbitrary organic compounds from one solvent to the other is introduced. We demonstrate the method’s usefulness and performance on $\mathrm{p}K_\mathrm{a}$ conversions involving water and organic solvents acetonitrile ($\ce{MeCN}$), dimethyl sulfoxide ($\ce{Me2SO}$), and methanol ($\ce{MeOH}$). We focus on the $\mathrm{p}K_\mathrm{a}$ conversion from the known reference value in water to the other three organic solvents, although such a conversion can also be performed between any pair of the considered solvents. The ECM works with an additive parameter that is specific to a solvent and a molecular family (essentially characterized by a functional group that is titrated). We formally show that the method can be formulated with a single additive parameter, and that the extra multiplicative parameter used in other works is not required. The values of the additive parameter are determined from known $\mathrm{p}K_\mathrm{a}$ data, and their interpretation is provided on the basis of physicochemical concepts. The data set of known $\mathrm{p}K_\mathrm{a}$ values is augmented with $\mathrm{p}K_\mathrm{a}$ values computed with the recently introduced electrostatic transform method, whose validity is demonstrated. For a validation of our method, we consider $\mathrm{p}K_\mathrm{a}$ conversions for two data sets of titratable compounds. The first data set involves 81 relatively small molecules belonging to 19 different molecular families, with the $\mathrm{p}K_\mathrm{a}$ data available in all four considered solvents. The second data set involves 76 titratable molecules from 5 additional molecular families. These molecules are typically larger, and their experimental $\mathrm{p}K_\mathrm{a}$ values are available only in $\ce{Me2SO}$ and water. The validation tests show that the agreement between the experimental $\mathrm{p}K_\mathrm{a}$ data and the ECM predictions is generally good, with absolute errors often on the order of 0.5 $\mathrm{pH}$ units. The presence of a few outliers is rationalized, and observed trends with respect to molecular families are discussed.

For example, $\mathrm{p}K_\mathrm{a}$ values of phenol in water, DMSO, methanol, and acetnitrile are illustrated in following diagram:

pKa values of phenol


Reference:

  1. Emanuele Rossini, Art D. Bochevarov, Ernst Walter Knapp, "Empirical Conversion of $\mathrm{p}K_\mathrm{a}$ Values between Different Solvents and Interpretation of the Parameters: Application to Water, Acetonitrile, Dimethyl Sulfoxide, and Methanol," ACS Omega 2018, 3(2), 1653–1662 (https://doi.org/10.1021/acsomega.7b01895).
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    $\begingroup$ Seems these are the values for water - not quite what they are in organic solvents, also seems OP needs more practical answer... $\endgroup$ – Mithoron Jul 16 '20 at 19:35
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    $\begingroup$ Thank you for your time and answer. I will not mark this answer yet, will wait for one day if someone wants to answer too. I too have calculated this value, since this gives some guidance to what is happening in this situation. The only thing comes to my mind is that these constants are in water. I remember some literature claiming that in glacial acetic acid HCl is a very weak acid, so possibly this calculation result is far from reality, since i would be using EtOH as a solvent, an overwhelming number of EtOH molecules would further hinder the dissociation of t-BuOH. $\endgroup$ – Andrew Kovács Jul 16 '20 at 19:38
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    $\begingroup$ Very nice addition to your answer, this is certainly more than i bargained for. $\endgroup$ – Andrew Kovács Jul 17 '20 at 8:12

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