Use minimum amount of DMF for reaction just for solubility of your compound. And workup use more washes with water.

Extract with ether or any solvent that has a less density than water, then wash your organic solvent with brine which due to its higher density than water can help in removing most of the DMF amounts remained in your organic solvent

Second, while drying under vacuum, add some pentane then use the vacuum pump, do that several times where the high volatility of pentane helps in the evaporation of DMF as well

if your product is not soluble in a specific solvent, such as ether, just try to crystallize or precipitate your product 

Normally....vacuum distillation should do well

First, if your product is not too polar, try using diethylether instead of ethyl acetate and washing 2 or 3 times with water. Typically, if you have 10 mL of DMF in your reaction, you could add 100 mL of ether and wash with H2O (3 x 50 or 100 mL). That should remove most of the DMF.

If you wish to remove it completely and if your product is not too coordinating (i.e. if it is not a carbamate, an amine, an amide...), then you can use saturated copper(II) sulfate aqueous solution for the washings, as it will form a complex with DMF.

All the above suggestions should work, but the easiest way I've found to remove DMF is to do several washes with water, then a final wash with 50% brine. I generally use 10-fold volume of water washes to work up a DMF reaction, in other words, 10 mL water / 1 mL DMF. In large scale reactions, I first concentrate the reaction mixture as much as possible on a rotavap. On my system, DMF will evaporate at ~ 50 deg C, so if your compound is stable at elevated temperature, you can give that a try, large scale or not.

Hope this helps!

I would add the following

1) it will depend on your scale and nature of the product. On a big scale, it is often possible to cleanly precipitate your product by slowly adding water to the reaction mixture, which replaces all the extractions and concentrations, you just filter your product and dry it.

2) If the extraction is unavoidable, can you use a mixture of EtOAc and heptane, say 1:1? The reason is two-fold: a) you reduce polarity of the organic phase, which helps in pushing DMF into the aqueous, and b) DMF is removed by evaporation with heptane quite easily (at this point I do not remember if it forms an azeotrope with heptane, you can check that). In general one good approach in such cases is to find a lower boiling solvent which can be azeotroped with your high boiling solvent.

I hope this helps,

Jacek

first ,use CH2Cl2 to remove your product from DMF, then use enough water to remove most dmf. then use brine to remove the dmf completly

On the other hand, CH2Cl2 dissolves DMF rather well...

may be use EtOAc is better, i usually use CH2Cl2

Thanks to all for their valuable suggestions. 

Replace EtOAc by alkane solvents  (like hexane) - they are not mixable with polar aprotic solvents (DMF, NMP, DMSO...)

You can rotarvap using high-vac at 60 degree C  & mix your DMF solvent with toluene. Which make the enter solvent B.P low and evaporate as azeotrope mixture. 

You can wash your reaction mixture repeatedly with cold water because DMF has a tendency to miscible with water...............

If my compound is soluble in DMF, then it means, if I dilute the DMF with water, it will remain in that portion containing the DMF and water. Isn't it?

Saikat,

Not necessarily - your compound most probably is also soluble in other solvents, too.

Saikat,

Like Jacek said, it's all about partition, unless your compound is water soluble, it most like to be more soluble in organic solvent, so in the presence of organic solvent it'll be more happy in organic layer.

usually what people do it to wash the organic layer with water about 3 times then brine wash, that should get rid of MOST of DMF, then a column or silica plug should remove last bit. I use hexane or Et2O to perform the extraction as long as I can, DMF usually dont go into those, save me some mutiple water wash. 

the best way I found to remove DMF of a reaction, is to make an azeotrope with Toluene. You should add two or three volumes of Toluene for one volume of DMF to completely remove the DMF without use a hight temperature.

I found DMF with Toluene easiest way to completely remove DMF from the reaction mixture. In 20 ml of DMF, i just added 30 ml of toluene evaporated at 55-60 o C and that worked for me. Thanks alot.

Can use 3 equivalents of Toluene relative to the DMF volume and rotavape at 50 o C (in water bath) at a pressure of 200 mbar. This worked pretty well for me.

Daniel,

Of course, as with any distillation, the distillation temperature will depend on pressure... Also, was it bath temperature or inside the flask?

e use freeze-drying, or lyophilization, as a way to remove solvent after rotovaping. If you have access to the equipment, this is a great approach. I bought my equipment for little money on the used market. Just remember to change the pump oil. Best wishes, Jim

Thanks for valuable suggestions.

Traces of DMF can be removed completely under Vacuum distillation only

Thank you, sir

DMF can be also removed from reaction mixture during extractive work-up by washing organic layers with saturated LiCl aqueous solution.

Try to quench your reaction mixture with crushed Ice and extract with thrice the fraction of ethylacetate and afterward concentrate organic layer on rotavapour. Most of the time you will be able to get rid of DMF but in case if your product is not polar in nature then use antisolvent technique for example: 1:9 EA/ HEX to precipitate your product and with this technique we can get rid of DMF completely, but if reaction is not complete and you have only 50-60 % conversion to product then use column chromatography to purify your product.

You can remove DMF completely by adding cosolvent like Toluene in round bottom flask during evaporation by rotary evaporater

Dear friend, you try to wash organic layer 3 or 4 times brain( Nacl+ water) solution DMF will remove

Washing with brine several times or washing with 10% LiCl (aq) works pretty well for me.

Saad Abdulrahman Hussain

Wash the reaction mixture during work up using diethylether.

Depends on your clean-up. If you are doing a DCM:MeOH after, then it isn't really necessary. Though, I have been able to do by diluting the reaction mixture in DCM and then extracting with water. The DMF will prefer the water layer but your products should prefer the DCM. Of course, this is what you do if you can't rotovap off your DMF at either high pressure/50C, if your products are T sensitive or have a low E of vaporization.

Added another solvent as co solvent to decrease b.p of DMF

Then evaporated by rotary evaporater

added small amount of ethanol then using rotary evaporator to remove all solvents until dryness.

High Vac works perfectly well...Then extract the residue with either DCM or EtOAc and wash with water and brine to remove any residual amount left.

Added another solvent to quench your reaction mixture with crushed Ice or cold water slowly .

Ya ,Its a good experience first add toluene in reaction mixer and then evaporate it by rota DMF Will go easily

https://books.google.iq/books?isbn=0123822408

Dissolve your product in dichloromethane then extract a few times with water. That will work. It should be absent by proton NMR this way. DMF is water soluble so it can partition between water and an organic solvent hence the need to do more than one extraction with water.

(i) while using DMF as solvent, it is better not to do EtOAc/ water workup. just add cold to normal water slowly with stirring. can filter n recrystallize the obtained ppt.

(ii) Don't shake the Sepa funnel vigorously to extract. u just revolve the sepa slowly by holding at key.u can observe the dmf is coming into water layer

(iii) Azeotrope with toluene n evaporate through rotavap

(iv) while doing evaporation through rotavap, make a small leak at joint n rotate.

Dissolving the product with DCM and then extracting with water for 3-4 times works for me to remove DMF from the product.

Ss

add toluene then do water workup then evaporate it by rota

add other solvent such as toluene then evaporate it by rota several times...

other wise use lyophilizer

So, my product is basically polycaprolactone (PCL) conjugated with some peptides in a solvent of DCM/DMF (50:50 mixtures) in presence of triethylamine (TEA) as proton scavenger. To remove TEA, first I add some amount of 0.1 M HCl in the separatory funnel, then slow add my polymer solution in DCM/DMF dropwise (slowly) into HCl.(If not added slowly dropwise, the boundary betwen the two phases is very difficult to visualize) This makes the DMF preferentially phase out into the aqeous phase (HCl) and the organic phase (DCM +PCL) settles down to the bottom (turbid/milky solution) of the separatory funnel. Separate the two phases and continue the above steps for a few times and DMF gets removed a very good extent. Once the DMF has been removed to a good extent, the organic phase can be added to the aqueous phase and vigorously shaken. Finally, separate the organic phase and dump it in cold diethyl ether/methanol to precipitate the product.

DMF can be completely removed after completion of reaction by distillation under reduced pressure.

You may try ice-cold brine solution and EtOAc for extraction.

To remove DMF completely after completion of reaction you can carry out distillation under reduced pressure.

I think you add some cold-water and then and EtOAc for the extraction or removed after completion of the reaction by distillation under reduced pressure.

I think you can dissolve the product with toluene or DCM and then extract with cold water for 3-4 times. Afterward, doing evaporation by rotavap will remove the DMF.

DMF is completely soluble in water u can remove by solubilizing in it and after extract it by ethyl acetate.

If your product is solid, I would highly recommend using a high vacuum rotary evaporator and a 75 °C hot water bath.

📷

I used to prepare some polymer electrolye membranes for fuel cell application and I performed some experiments using DMF as a solvent. I removed this solvent from the resulting products through either distillation or vacuum rotary evaporation.

DMF usually removed completely by dissolving the product in distilled water and stirring the solution for an hour then separate the solid product by filtration, If the product oily separates it by extraction with ethyl acetate.

Better to dissolve your product in non-polar solvent if it dissolves.

Thank you

Before the work-up you need to remove polar solvents like DMF or else there'll be a significant loss of yield. If available, DMF can be azeotropically removed using n-heptane.

Otherwise, add an equivalent volume of DI water, and leave it on the house vacuum overnight in a water bath set to 35C.

I experienced . please try as given below.

After complete of reaction, u can work up with ice water and extracted with EtOAc (Don't make vigorous shaking, the solutions becomes turbidity). Do workup twice or thrice as same. Collect combined organic layer and dried with Sodium sulphate. Evaporate the organic layer under rota-evaporate to get DMSO free product.

I agree with Donka. You can remove by using ice cold water instead of normal water in workup process

I would add water and dichloromethane or ether, which is more convenient coz it’s lighter, and extract the organic layer 2-3 times with water. The DMF will partition into the water

Just do workup with Ethyl acetate and water and at last wash it with brine. If you use DCM, then it will have more DMF content so avoid using DCM. Then concentrate everything and at last when DMF was left in residue, add 4:1 mixture of toluene and water (should not be precise) into the residue and evaporate around 45-50 oC, you will get solid product easily.

but my product is also soluble in water, won't there be a loss of yield?

DMF usually removed completely by dissolving the product in cold distilled water and separate the solid product by filtration.

Purge argon or nitrogen or just air at a high speed. I even evaporated water and DMSO this way.

Avula srinivasa rao : If you can substitute formamide for DMF you should have much less of a problem.

DMF can be washed away by washing with methanol multiple times.

If product is insoluble in water then we use cold distilled water in sample and filter it but if product is also soluble in water then it is insoluble in aliphatic solvents so we can use heptane for removing DMF

I agree well with Prof. Shilpa Yadav, it is a very suitable method for removing DMF practically.

When removing DMF, workup with ethyl acetate, distilled water, brine and boiled water.

I was facing the same problem. After using High Vacuum, organic compound was free from DMF. No DMF peak on 1H NMR. Hope this works for you as well. @Avula

It depends on the amount of DMF used. If it is in a small amount then even ethanol is enough otherwise you have multiple options as I already mentioned above and others too.