EDC.HCL CAS 25952-53-8 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride

There are mainly three kinds of commonly used condensing agents: dicyclohexylcarbodiimide (DCC), diisopropylcarbodiimide (DIC) and 1-(3-dimethylaminopropyl)-3-ethylcarbon Diimine (EDCI). The use of this type of condensing agent generally requires the addition of an acylation catalyst or activator, such as DMAP, HOBt, and the like. Since the addition intermediate of acid to carbodiimide is not stable in the first stage of the reaction, if it is not converted into the corresponding active ester or active amide without an acylation catalyst, it will rearrange itself to the corresponding stable urea. by-product (Pathb).

Condensation activator: The commonly used condensation activators are as follows. At present, 4-N,N-lutidine (DMAP) has been widely used to catalyze various acylation reactions. Sometimes when the catalytic effect of DMAP is not good, 4-PPY can be used. According to relevant literature reports, its catalytic ability is about a thousand times higher than that of DMAP.

Among the three commonly used condensing agents, DCC and DIC are cheaper. Generally, DCC and DMAP are used together. The biggest disadvantage of using DCC is that the other product of the reaction, dicyclohexylurea, has a small solubility in the general organic phase but is slightly soluble. Therefore, through some common purification methods, recrystallization, It is difficult to remove it completely by column chromatography, etc. Since the solubility of dicyclohexylurea in diethyl ether is relatively smaller than that of other solvents, it is generally necessary to evaporate the reaction solvent and then add diethyl ether to filter out most of the dicyclohexyl urea. Dicyclohexylurea is then further processed. DIC is generally used in solid-phase synthesis of combinatorial chemistry because the diisopropylurea it produces has good solubility in common organic solvents.

At present, EDCI is most used in medicinal chemistry. One of its main features is that the urea produced after the reaction is water-soluble and can be easily washed off. Generally, EDCI is used in combination with HOBt (note: this reaction HOBt is generally Indispensable, otherwise the condensation yield may be too low). Sometimes if the a-steric hindrance of the acid is large or there is an electron-withdrawing group attached, the reaction will stop at the active ester step (the active ester has a strong mass spectrum signal and can be detected by MS or LC-MS).