[discodermolide]

Well you can't reflux conc. (96%) sulphuric acid. But this may be the better reaction, you can do it at lower temperatures.
[/quote]
I'm wondering why you cannot reflux sulfuric acid?  I remember doing a synthesis of isopentyl alcohol via fischer esterification many years ago and we refluxed a mixture of isopentyl alcohol/acetic acid and a small catalytic amount of sulfuric acid (~ 1 mL) just fine.

Bad idea?
[/quote]

Well 1 mL of conc. sulphuric acid is hardly refluxing sulphuric acid!

[asdfTT123]

Alright, I will give this a try if the acid catalyzed fischer esterification fails.  Do you mean to destroy the excess SOCl2 collected via rotovap with propanol?  I can't simply discard it through my halogenated waste jug?

There are several good responses on here - some active-ester routes, some Fischer esterification. I just wanted to say, FOR THE LOVE OF GOD DO NOT DO THIS. You will cause a lab disaster.

To dispose of excess SOCl2, slowly drip it into aqueous base in a FUME HOOD from a dropping funnel or similar.

Can you reiterate what I should not do and why that is?  Sorry, im a bit confused as I stated two things in the quote that you posted.

[asdfTT123]

Sorry for the barrage of posts guys, but I'm really trying to figure this out before I leave lab this weekend.

I checked the TLC of the HCl catalyzed fischer esterification I have going on.  Dipped a little straight out of the reaction and ran it on 4:1 EtOAC:Hexanes.  The TLC streaked really badly but I saw basically two spots.  The higher one, which I presume is the ester product is still lighter than the bottom spot.  The bottom spot is at the starting point of the TLC and streaks upwards about 1/4th of the plate.  Why is the plate streaking?  I'm spotting a very minimal amount.

Anyways, the TLC only looks slightly better than the one I ran yesterday before I left lab (i.e. the top spot is a little darker) and I doubt refluxing over the weekend will do much to improve my yield.  So I was thinking of just rotovapping away the solvent and replacing with fresh anhydrous 200 proof EtOH and adding a catalytic (4 mL) of sulfuric acid and then refluxing.

Thoughts?

[discodermolide]

Perhaps you should change your TLC solvent to a DCM/Methanol mixture, say 5% MeOH.
If the reaction is working, albeit slowly, just leave it refluxing over the weekend, if you are allowed to to that.

[opsomath]

Sorry, I meant that under no circumstances should you place UNREACTED thionyl chloride in the waste. It will break down to SO2 and HCl, probably bursting or geysering the container, and you will have the worst mess ever on your hands even if no one is injured.

I agree with your idea to rotovap it down, then refill with H2SO4 (a good dehydrating acid) and more absolute alcohol. Make sure your absolute is fresh and/or stored over sieves. You are basically describing a crude replacement for the Dean-Stark trap. (You don't have one of those handy, do you?)

The use of an alcohol to quench the excess thionyl chloride is okay too. I don't recall the precise procedure we used for this, so I refrained from mentioning it.

I agree with switching to a chloroform/MeOH or DCM/MeOH TLC solvent. You are thoroughly drying the TLC plates before running them, right?

[asdfTT123]

Perhaps you should change your TLC solvent to a DCM/Methanol mixture, say 5% MeOH.
If the reaction is working, alhttp://www.chemicalforums.com/Smileys/classic/huh.gifbeit slowly, just leave it refluxing over the weekend, if you are allowed to to that.

Yes, it does appear to be slowly working but my impatient self is wondering if it's worth it to rotovap away the liquid and replace with anhydrous EtOH + catalytic sulfuric acid.  I suppose just check the progress on monday?

Also, I just tried running the TLC with DCM and methanol and although it still streaks, it streaks much less, thanks.  From the TLC, the reaction is still less than 50% to completion.

[asdfTT123]

Sorry, I meant that under no circumstances should you place UNREACTED thionyl chloride in the waste. It will break down to SO2 and HCl, probably bursting or geysering the container, and you will have the worst mess ever on your hands even if no one is injured.

I agree with your idea to rotovap it down, then refill with H2SO4 (a good dehydrating acid) and more absolute alcohol. Make sure your absolute is fresh and/or stored over sieves. You are basically describing a crude replacement for the Dean-Stark trap. (You don't have one of those handy, do you?)

The use of an alcohol to quench the excess thionyl chloride is okay too. I don't recall the precise procedure we used for this, so I refrained from mentioning it.

I agree with switching to a chloroform/MeOH or DCM/MeOH TLC solvent. You are thoroughly drying the TLC plates before running them, right?

Thanks again your your help and the tip with the thionyl chloride - I'll def keep in mind if I need to use it again.

Yeah, our lab is very basic...I'm the only one here with any organic synthesis experience (but not much) so we don't have a Dean-Stark setup.  I bought the very basic equipment to do some simple synthesis.

Yep, I'm trying to thoroughly dry the TLC plate before running it.  I will try using a heat gun to dry more thoroughly if needed.

I'm thinking if I don't see much more progress this afternoon I'll rotovap and replace with anhydrous/absolute EtOH + sulfuric acid.  About how much sulfuric acid do you think I may need if the reaction volume is ~100 mL of EtOH?

[orgopete]

Although I like the idea of using conc sulfuric, unless the literature is is really old or from some obscure laboratory, the 85% yield may reflect some special requirement (or the slowness consistent with the unfavorable equilibrium created by the excess water).

Given the lit yield is 85%, I might add more anhydrous alcohol just to sway the equilibrium. I'd add a lot more.