Depends on boiling point and solubility of your product. If applicable, you can remove the main part of SOCl2 by distillation and subsequently add water into a solution of your product in an organic solvent.

Michal, thank you for reply.

The thing is I wanted to avoid evaporating of excess of SOCl2 on a rotovap. I thought about adding formic or acetic acid to the mixture to cause the esterification to methyl acetate/formate (the reaction runs in methanol) but I am not sure if it works.

SOCl2 is usually used to transform an alcohol into an halide or an acid into an acyl chloride. Indeed, these two reactions have thionyl "esters" (or mixed anhydrides) as intermediates ... However, these intermediates are never isolated since Cl– (chloride anion) reacts immediately on them to elimintate (SN) the thionylester residue and to yield the desired halides.

Thus, I wonder if the "esterification"word you used means this kind of ester or the ester of an alcohol you can easily obtain by using the prepared halides ?

By the way, to my experience, such thionyl chloride is quite difficult to hydrolyse ... in acidic medium. You better try to get this hydrolysis by getting an alkaline pH.

Thank you for reply,

The reaction I perform is an esterification of N-CBZ-proline with methanol, using the N-CBZ-prolyl chloride generated with SOCl2 (adding SOCl2 to methanolinc solution of amino acid derivative). As a large (3-fold) excess of thionyl chloride is used, I wondered if there is any mean to decompose it (thus, removing the excess of reagent by rotovap could be avoided).

I thought about addition of eg. acetic acid to the mixture to convert it to acyl chloride, that would react rapidly with methanol. So, "esterification" word I used related exactly to the ester of an alcohol.

Ice and water, slow mix

Have you been unsuccessful trying to get the N-CBz prolyl methyl ester simply by adding 1 drop of H2SO4 (concentrated one ± 12 N) into the fully anhydrous methanolic solution of the benzamide? If it does not work at room temperature overnight, you even can heat it up to reflux in the same conditions for an hour or so ... I bet you no longer will have problem with SOCl2 destruction of the 3 equivalents you use.

Take your chance, ... tonight and see tomorrow!

I understand your aim is to make an ester from an acid via the corresponding acid chloride. In such cases excess thionyl chloride is normally removed from the acid chloride by adding a suitable dry solvent in portions and repeated distillation. Obviously, suitability of this process will depend on the boiling point of the acid chloride.

Thak you for all the answers

@ Eugen N. Krylov - Anyhow, I will then have to get rid of methanol on rotovap. I fear adding water to an acidic solution of the ester and then heating it during evaporation can cause some decomposition.

@ Prof. Vercauteren - I have added SOCl2 prior to asking this question.

I found this on the web:

"One of the great advatages of this over other chlorinating agents such as PCl3 or S2Cl2 is that only gaseous byproducts are formed, while the last reaction can be used to destroy any left over thionyl chloride reagent without the need for a distilation."

And the "last reaction" was: HCOOH + SOCl2 --> 2 HCl + SO2+CO

I will see if this works. Thanks again!

Dear Maciej, have you consider concentration under high Vac, so you could do it at room temperature, even at lower temperature.

If this is not an option, Ice and water should do the trick. Good luck

Ice and water, slow stirring

Addition of excess MeOH will give you HCl and Me2SO4

Neutralise with NaHCO3 upto Ph 6.5-7 and extract with DCM and If you gone upto PH 8 under cooling conditions, SOCl2 with quench and extract your desire into DCM or your freely soluble solvent, and isolation. If reaction is reversible, whatever formed 1 or 2% starting material will go to basic or water. Other wise Give thoroughly water washing upto your water PH should be Neural, in your product N-is protected.(I think it won't go acidic water), SOCL2 is water soluble.

Slow addition or control addition of the reaction mixture having excess thionyl chloride to the aqueous solution of sodium carbonate or sodium bicarbonate at 10-20°C. After neutralization, filter it or extract with the suitable solvent like ethyl acetate or dichloromethane.

On 5-10Kg scale runs I find pouring onto a large excess of ice (around 20-30Kg) is pretty good. Leave to stand, stir occasionally then separate (cut away) aqueous. Assumes your product is stable to aqueous acid........ Adding water directly is extremely hazardous. John Johnson Appleton Scientific

Usually an aspirator (pump) works fine to remove an excess of thionyl chloride (use safety bottle!).

As you know you can do esterifications a larger excess of alcohol – dissolve/suspend your compound and add 1 drop of DMF and finally add thionyl chloride slowly.

By the way, the reaction of thionylchloride and alcohol gives, for example, dimethyl sulfite:

OSCl2 + 2CH3OH → OS(OCH3)2 + 2HCl

To my opinion (as already said above) the best soution is to distill away the tionyl chloride in excess.

This can be accomplished either simply rotavaporing the solution, first to eliminate the most of it, then resuspending a few times the crude with anhydrous toluene and strip the residue away ... optimizing the reaction conditions will help reduce the necessary amount of SOCl2. Using this procedure I never had problems in interferences from residual SOCL2.

Also at least at the beginning if not sure you can check the acylchloride / ester or whaterver compound you are willing to synthesize by IR to assess whether or not there is still some SOCl2......

Just one question i do not understand why should it be still thionylchloride if you already performed an esterification; or else ... excess SOCl2 must be removed before any opther action (usually)....

Best regards

I used thionyl chloride because of its availability (in a good grade) in our lab and also because this time I wanted to follow literature protocol.

I have performed esterifications with this reagent many times. Each time I used rotovap to remove excess of reagent (evaporation, then coevaporation with 5xdry PhMe) and this was efficient. This time I simply started to wonder if there are any ways to decompose this toxic reagent in the post raction mixture..

In my experience i rarely use thionyl chloride for esterification becouse usually l want methyl or ethyl esters

thus if much more easy to reflux 1-2 hours the compound in the corresponding alcohol with few drops of fuming H2SO4 (or HCl 37% ).

in case of more bulky or heavier alchool i use CDI or WSC or DCC (1.05-1.2 eq activation for 1-1.5 hours r.t.) then the alchool

.... obviously you can use SOCl2 to activate the acid but then to destroy it after activation and before alcohol addition and contemporary sparing your acyl chloride it practically impossible ....

The only way I can think of it could be the case in wich

1) your acid is soluble in the reaction media (for example THF SOCl2)

2) the acylchloride produced instead is solid (which in turn is not impossible but quite rare provided that usually acyl chlorides are mole lipofilic, thus soluble in org solvent, than corresponding acid ) thus it can separate ...and you can filter it off and wash away the excess SOCl2

Alternatively you can use a large excess of the alcohol and contemporary destroy the XS SOCl2 and form the ester ... but still can be tricky insomuch the acidity developped and the heat may harm your final ester compound or you may have to waste a substantial excess alcohol (maybe a valuable one)

Regards

I usually evaporate the reaction mixture directry, and co-evaporate with DCM or solvent used for the reaction. Excess thionyl chloride should be removed.

The best option is to concentrate the excess thionyl chloride at 20 degrees with rotovapour. then co-evaporation with DCM works best

Add Sodium Bicarbonate to neutralize excess thionyl chloride. After neutralization quench the product by water immiscible solvents (Chloroform, DCM, Ethyl acetate) and add water. Separate the product using separating funnel (bicarbonate removed in water). Beware your product must be soluble in above mentioned solvents.

Caution should be exercised that both the flask containing product and methanol (which is to added) must have cool 0-50C, so that minimum vapors will produced.

Dear Maciej Dawidowski,

As Jatinder said, alcaline treatment is the prefered mean to "hdrolyze" this equivalent of an "acyl chloride" (thionyl chloride). However, its reactivity towards such a reagent is not so fast as it could be thought about! Even though it is always said that "it reacts violently with wather", it takes time to get it fully destroyed: residual thionyl chloride in the crude mixture after evaporation of the solvent, confers acrid (unpleasant) smell, that is characteristic. In our hands, one could get rid of this residual reagent (no more smell), by a prolonged hydrolysis time in alkaline solution.

I just wonder which step of your "esterification process" is concerned that would still admit the presence of SOCl2?

Sincerely,

Joseph Vercauteren

The easiest way to remove the excess thionyl chloride is to concentrate the reaction mixture with rotavap connected to potassium hydroxide trap.

Yes. Just like my boss Mr. Jude Ayogu said; concentration with rotavap connected to KOH trap is good.

How could apply the trap of KOH or any other base to neutralise the thionyl chloride ?

I mean how to set up the Rotavap with this trap?

Thanks.

I used thionyl chloride for acid to acid chloride in ethylacetete solvent after reaction I want quench excess of SOCl2 using any alkali trap to quench untraped SOCl2 vapours

For decomposing residual thionyl chloride after esterification ,treat the reaction mixture with 10% aq. NaHCO3 ?

For decomposing residual thionyl chloride after esterification , neutralize reaction mixture with aqueous alkali like Na2CO3 the thionyl chloride is water soluble & HCl acid formed will be neutralized by alkali.