The reaction has to be done in a dry non aqueous solvent

Afaik no.-

I agree with Imthyaz Khan: it has to be in the absence of water or your reaction will occur between DCC and water, being a more powerful nucleophile, I think.

I agree with Imthyaz Khan: it has to be in the absence of water or your reaction will occur between DCC and water, being a more powerful nucleophile, I think.

Dicyclohexyl carbodiimide and its analogues interact with carboxylic/carboxylate group selectively. Presence of water have not effect on the course of esterification with use of sterically hindered alcohols. Some DCC analogues are dedicated for action in water.

See http://en.wikipedia.org/wiki/N,N%27-Dicyclohexylcarbodiimide and citations herein.

1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) can be used in water - see http://en.wikipedia.org/wiki/1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide.

Erny, please go to this site which shows the reaction mechanism

http://www.organic-chemistry.org/namedreactions/steglich-esterification.shtm

Well, you will see clearly that water molecule will indeed compete in the process thus cannot be used as a solvent for this reaction. Toluene and methylene chloride are suitable solvents for this reaction.

See-

---Journal of Molecular Structure, 1028 (28), 88-96, 2012.

---Tetrahedron, Volume 69 (10), 2319-2326, 2013.

Good luck

Dear colleagues,

Thanks a lot for the answers. I'll study it thoroughly.

Have a blessed ! :)

No water, use anhydrous DCC or DMF. See:

Hoefle G, Steglich W (1972) Synthesis 72, 619.

Hoefle G, Steglich W, Vorbrueggen H (1978) Angew Chem 90, 602

Neises B, Steglich W (1978) Angew Chem 90, 556.

Neises B, Steglich W, van Ree T (1981) SA J Chem 34(2), 58-59.

For peptides, add HOBt.

A problem connected with hydrolysis of intermediary 1-acylpyridinium cation by competitive attack of water molecule can be solved by realization of synthesis such as the “inverse phase transfer catalysis” (see Lon J. Mathias , Rajeev A. Vaidya, Inverse phase transfer catalysis. First report of a new class of interfacial reactions. J. Am. Chem. Soc., 1986, 108 (5), pp 1093–1094. DOI: 10.1021/ja00265a047).

It is by addition of solvent which is very bad mixable with water, e. g. tert-butyl methyl ether (tBME, MTBE).

1-(Pyrid-4-yl)piperazine (PyPi) is much better than DMAP for use in this and similar cases. PyPi is available at TauChem Ltd. Slovakia, [email protected].

You must use DCC and DMAP . About 2 or 3 haurs later dicylohexcyl carbourea precipitation observed. Water must not be use

Hello all,

Do you think I could use DCC/DMAP in anhydrous DMSO?

Thank you!