I forgot to say that I left the mixture stiring for 1 hour at room temperature.

Marian Popa,

1. More SOCl2 would be necessary.

2. Transformation of carboxylic acids into acid chlorides using SOCl2 usually requires to heat, while the same transformation using (COCl)2 doesn't.

3. Addition of catalytic amount of DMF is sometimes effective because it generates an active species, called Vilsmeier reagent.

4. Instead of mixing all the substrates from the beginning, addition of your amine to a mixture of the prepared acid chloride and a base such as Et3N or even aqueous NaOH (Schotten-Baumann method) is recommended. Without a base, your amino group is masked with HCl and no active (nucleophilic) lone pair is on your nitrogen.

5. Removing the Vismeier salt by the precipitation with hexane is sometimes necessary, if your acid chloride is soluble in hexane.

Most importantly, checking a couple of similar reactions in the literature before your experiments is highly recommended. Cheers!

I agree with the previous answer, it is important to know that SOCl2 forms SO2 and HCl with the moisture in your educts/solvents and also during the substitution of the acid-OH group. Therefore your amines will be present as Ammonium salts almost quantitatively. A nucleophilic attack thereby is no longer possible.

Use little overstochiometric amounts of SOCl2 to account for moisture, add DMF as catalyst and add the amines only after transforming carboxylic acid into acidchlorides.

Good luck with your synthesis.

Do I need to heat the mixture to obtain the acid chloride or to keep it on ice-bath/ room temperature?

Use 1 Eq carboxylic acid and 1,5 Eq SOCl2. Heat it and after a certain time distill of remaining SOCl2 or destroy it by heating under slight vacuum until no more gas comes of.

First draw out the reaction scheme and show all reagents and all products. Although this synthesis can be carried out in one pot it is a stepwise sequence and the amine should be added after acid chloride formation is complete. I suggest adding a catalytic amount of DMF to the reaction mixture to promote acid chloride formation then follow the reaction by TLC. The acid chloride is a low melting solid and can and probably should be isolated, but not necessarily purified, before using in the next step. The reaction of the acid chloride with the amino ester HCl will require the addition of a base eg Et3N to neutralize the HCl salt of the amino ester and HCl generated in forming the amide or it won't work. This step should also be followed by TLC. Both steps should proceed at RT but may require a little heat.

So I used an excess of SOCl2 and I refluxed the acid chloride with the amionoacid ester. The final product is an oily substance which I analized trowgh TLC and it's a new compund. I tried to precipitate it with hexane and that not worked.

Any ideea to precipitate the amide?

Marian Popa, I recommend that you check more than 5 papers that described the formation of acid chloride followed by amide more carefully. I'm afraid your confusion may have come from the fact that you are trying to set up the reaction only by your own way according to the advices from here (ResearchGate), without checking the experimental sections that dealt with the similar reactions, by yourself. How about considering learning the standard recipe, first? It would be difficult to precipitate only your target amide in the presence of many byproducts, including Vilsmeier salt. Instead of the attempt for the direct precipitation, what are many people doing? I intentionally do not tell you everything, but you probably have to know how to carry out and quench the reaction, and how to purify your target compound from the literature, which will be extremely beneficial for your future. Good luck!!

Kohei Torikai , I followed your pieces of advice and I studied around 10 papers regarding my subject. I have to mention that I did not use DMF( my lecturer which helps me with this said it would have been very hard to get rid of the Vilsmeier salt).

The main problem is that your amino acid is present as a hydrochloride salt, when you need the free amino group to react with the acid chloride. Treat it with sodium carbonate in water, extract the free base with ethyl acetate, and add the extract to the acid chloride solution (which you should prepare by separately reacting the thionyl chloride with aspirin.) One drop of DMF will suffice to catalyze the latter reaction, without interfering with the work-up.

My concern with neutralizing the amino ester before adding it to the reaction is the possibility of self condensation especially if the solution is not dilute.

Marian,

Your's reaction should work. Convert acid to acid chloride using excess thionyl chloride in dichloromethane at reflux condition. Distill it under rotary evaporator, add excess of acid free alanine ester (can obtain from work up with NaHCO3 solution) and triethylamine and allow to stir until the conversion of acid chloride to product.

Krishna Reddy , do I need to heat up the mixture in order to obtain the amide? I tried at 55 Celsius...it is possible that this temperature is too low?

Marian Popa, no, you don't need to heat the reaction. Room temperature is fine. If you couldn't get your target material, the problem must lie in the acid chloride preparation. Check the clean formation of acid chloride by NMR or other spectroscopic methods.

I had obtained a yellow-brown oily substance and I tried to precipitate it using dichlormethane( to dizolve it) and hexane to precipitate this. And that does not worked. I tried using ethylacetate and hexane and the result was the same. This substance is soluble in dichlormethane, chloroform, ethylacetate and ethanol.

Any idea to precipitate it?

While researching the literature I have found the some amides like my own are oily fluids.

Marian Popa, you don't have to precipitate it. Take the 1H-NMR spectra of the yellow-brown oil and your starting material (carboxylic acid). Then compare them. Can you find any difference?

Thionyl chloride (SOCl2) seemingly could have become contaminated with sulphur chlorides, including disulphur dichloride (S2Cl2); possibly due to its thermal decomposition.

So this is the IR spectrum for the yellow-brown oil. The peak at 3329 it's the -NH bond from the amide structure I think based on which absorbtions I found. And this is different from the IR spectrum of aspirin.

1H-NMR is highly recommended. IR spectrum of a mixture tells little.

Marian,

Take NMR and mass spectral analysis. IR spectrum alone does not gives confirmation.