[Panoramix]

I am currently trying different conditions for a Suzuki coupling, both with boronic acids and esters, with an aryl bromide.

Usually the reactions are performed on 0.5 mmol scale with approx. 2 ml of solvent (THF or dimethoxyethan/H₂O) at reflux temperature.

No matter how much precaution I take the solvent evaporates overnight and most the reagents are destroyed.

I usually use a 5 ml flask with a Dimroth condenser which is closed on the top with a septum. I do not use grease as I found it a couple of times in my product and separation was close to impossible.

Any ideas?


Thanks a lot..

[Mitch]

I would put grease as a small ring at the very top of the joint and I would wrap the joint in parafilm. I would then attach copper wire bow ties to the top and bottom of the glass ware. I would then wrap rubber bands around the two bow ties insuring a very tight seal.

[movies]

It's usually not really necessary to have complete reflux.  I would just drop the temperature of your bath by 5 degrees so the solvent doesn't actually boil.  You won't lose much energy.  Five degrees is something like 0.5 kcal.

[kiwi]

in similar situations i either (a) drop below reflux and run the reaction in a sealed vial or (b) run the reaction in a flask, but seal the joints with teflon tape (aka Threadseal, the white non-adhesive tape plumbers use to seal threads in pipe connections - available for about $1 at any home supply shop). just place a single turn around the top of the condensor joint, and place firmly into the flask as usual. the teflon will deform to seal the gap. This is about the ony way i keep small volumes of dcm at reflux for extended periods. a word of caution - if you push *very* hard the extra thickness of the condenser will crack the recieving joint, for the first few times i'd have a spare dry flask ready to rock just in case.

[Custos]

This highlights an interesting misconception, often shared by students in organic synthesis. There is nothing magical about a solution under "reflux". Reflux is merely a convenient way of setting a known temperature. So for example no matter how much you heat benzene under reflux, the temperature of the reaction will not go much above the boiling point of 80 degrees. That makes the reaction set-up easy if you need an 80 degree reaction. However, there is nothing to stop you from doing the same reaction in toluene and setting the temperature of an oil bath at 80 degrees. The reaction proceeds the same -- refluxing has no special effect.

So to solve your problem I agree with the other posts - you could reduce the temperature of the reaction, although with small volumes you might still have evaporation problems. The easiest solution for small volumes is to use a sealed tube or sealed reaction vessel, and control the temperature with controlled heating (e.g. an oil bath with feedback thermometer) to just at or below the solvent boiling point.

[kiwi]

oh and i also forgot to mention, if you are going to be spending a while doing this sort of thing, get your glass blower to make up some reaction tubes eg. i have a range of quickfit test tubes ~10-15 cm long, and 15-25mm across, fitted with B10 or B14 joints. The bottom of the tube is either rounded like normal, or shaped into a bulb, either rounded like a round bottom flask or pointed like a pear shaped flask (for very small volumes). some also have sidearms (these are no good for reflux, but are awesome for reactions at -78 degC). the long length of the tubes allow the solvent to condense mostly on the walls rather than inside the joint (i still use a taped condenser though), and helps for when things need to reach inside an oil/cold bath while still being easily clamped. i use these for anything 0-5 mL above or below ambient temp, and they are way better than baby round bottoms for this. they are also of use for very small scale reactions (eg. 50 uL a few days ago in a pointed one). i can post a photo to copy if you want.

[ptb969]

I used to do some experiments like the one you are doing.
However, I took solvents that have higher boiling point and at refluxing there was no problem with losing solvent.
You are using here THF having quite low boiling point (65°C). Probably, it may work if you used cooled water for your condenser, on the other hand, I found the double-walled condenser helpful too.
I wish you best luck.
PTB969

[Panoramix]

Thanks for all the suggestions!

I will try the method with teflon tape just with solvent and no reagents tonight.

We are just a poorly equipped medicinal chemistry lab and our glass blower was the latest victim of budget cuts. So no way to get special glassware and our heating baths do not have feedback thermometers. This is why I prefer reflux, it is a self adjusting system.

[Panoramix]

Thanks for the hint with the teflon tape!
A 10 ml flask, a stirring bar and a few mL of THF were connected with a condenser.
The lower joint of the condenser was wrapped with a single layer of teflon tape as well as the septum closing the upper part. The septum was sealed with Parafilm.
After refluxing overnight most of the solvent stayed in the flask.

The loss is acceptable, perhaps a new septum would help, too.

Another problem solved....