It seems you want only one amino group to react? If so you will avoid the problem of separating out a large excess of H2NCH2CH2NH2 if you use a monoprotected ethylenediamine, and deprotect afterward.

In Organic Synthses (2007, v 84, p209) you'll find an efficient procedure for making BocNH(CH2)2NH2. Reaction of this compound with your methyl ester may proceed smoothly in refluxing methanol, but if you have slow- or no reaction, then use a Teflon-plug sealable tube (see Ace Glass catalog) - which will let you safely* heat MeOH solutions to at least 100 oC. (Ethanol boils higher but will likely exchange ethyl for methyl ester, and depending on how you monitor ester disappearance this can complicate reaction monitoring. The ethyl ester will also be slightly less reactive than methyl.) Removal of the Boc group can actually be done without isolating the N-Boc-N'-amide by using HCl formed from acetyl chloride reacting with methanol. This can be run in a separate container and the resulting MeOH/methyl acetate/HCl solution can be added to the crude amide mixture:

4-(C12H25O-PhCO2CH3 + H2NCH2CH2NHBoc -->

4-(C12H25O-PhCO(H)NCH2CH2NHBoc

(N-Boc-N'-amide)

MeOH + AcCl --> HCl + AcOMe + MeOH

combine to give 4-(C12H25O-PhCO(H)NCH2CH2NH3+ Cl-

-----------------------------

*Safety equipment required for sealable tube reaction includes an acrylic safety shield and heavy rubber gloves. Such reactions should always be run behind a protective shield. Ask for simple procedure for purging headspace with boiling solvent vapor and further safety instructions if this apparatus becomes necessary.

Thank you. In the publication mentioned, Boc is stable up to 85 °C so that a deprotection of the amine can occur during the amidation. I observed that when setting the heating plate to 110 °C MeOH starts to reflux.

Another question:

Shall I do the amidation of the ester in a nitrogen atmosphere?

Don't worry about the atmosphere - amines are subject to slow air oxidation, but if your ethylenediamine is a recently-received bottle there should be few impurities. The Org Synth procedure includes recommendations that you distill this if it's yellow. Impurities to be removed by distillaiton would have formed by reaction with atmosphereic oxygen, accumulating during storage, but unless you are using a very old bottle this is probably not necessary.

Dissolved air is driven out of boiling solvents and replaced by solvent vapor - you won't need an inert atmosphere during the reaction.

As to the temperature where Boc begins to decompose, remember the principle of refluxing solvent: the bulk liquid temperature will be only slightly higher than the boiling point of the solvent (some b.p. elevation will occur due to dissolved reactants and products) so regardless of the hot plate or bath temperature, a reaction mixture in methanol will probably have internal temperature of < 70 oC. Use an internal thermometer especially for the Boc protection of ethylenediamine. Also, the "reflux" you observe while your bath is maintained at 80 oC may be a very mild boil - pure ethanol boils just a couple of degrees lower.

Many many thanks. Indeed, our ethylendiamine bottle is very old and is yellowish. The boiling point is 118 °C. Which pressure do I need for the distillation? I assume a distillation via rotary evaporator is not possible so that I have to carry out a classic vacuum distillation.

You can do the distillation at atmospheric pressure if you choose. I would

introduce a slow nitrogen stream into the headspace of the still, making sure you do not heat a closed system.

For vacuum distillation, you will want to use a pressure between ~ 100 - 400 torr* If you can get a one piece short-path distillation head that will be the apparatus of choice. Check your vacuum pump with an empty apparatus to see if there is some pressure in this range that it likes to stablize at - if you need higher pressure, make sure you have a smoothly adjustable bleed valve. Ask around and see if any of your neighbors do vacuum distillations - they should have a bp/pressure nomograph for estimating boiling temperatures at reduced pressure and they can hopefully show you how it's used.

* make sure the boiling point is well above room temp, otherwise a significant amount may go into your vacuum system without condensing.

Thank you for the fast answer. I'll try the distillation at atmospheric pressure by introducing a slow nitrogen stream in a Schlenk flask containing the ethylendiamine if I correctly understood.

Hello.

I've another question. I would like to do a DCC coupling of PMAA (100 kDa) with an amine. I already found a paper where they dissolve PAA in NMP under stirring at 60 °C for 24h. In my case PMAA didn't dissolve very well in NMP - the solution is very turbid and there is a small precipitate at the bottom of the flask. I can't use water because DCC doesn't dissolve in it. Are they any recommendations from your side. I also tried the synthesis with EDC HCl in a mixture of THF/H2O but it didn't work well so that I would like to switch to DCC instead. Thanks in advance.