As it is known from the literatures 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, EDAC (CAS 25952-53-8) is commonly known as water-soluble carbodiimide (WSC) and is used as a versatile coupling agent to form amide, ester or thioester bond and thus to cross-link proteins, nucleic acids or to bind molecules to surfaces in aqueous or organic media. There are also examples in which WSC is used as water scavenger or as a reagent for heterocyclic ring formation.
Water-soluble carbodiimide exists in different forms as the free base, methiodide or its hydrochloride salt. The HCl salt is the most convenient form due to its long term storage stability and is only slightly sensitive to hydrolysis.
Kemilab is able to offer all three varieties, namely
1. 1-(3-Dimethylamino)propyl-3-ethylcarbodiimide hydrochloride – CAS 25952-53-8
Synonyms – Water soluble carbodiimide (WSC), EDAC.HCl, EDC, EDC.HCl
2. 1-(3-Dimethylamino)propyl-3-ethylcarbodiimide – CAS 1892-57-5
Synonyms – EDC, EDC free base, EDAC free base
3. 1-(3-Dimethylamino)propyl-3-ethylcarbodiimide. methiodide CAS 22572-40-3
Synonyms – EDC.MeI; EDAC.MeI
Serve as an example mechanism of coupling reaction of carboxylic acid with an amine using EDAC.HCl as coupling agent.
First an O-acylisourea intermediate is formed by the reaction of a carboxylic acid and the carbodiimide. The O-acylisourea is a highly reactive species that readily reacts with amines, peptide coupling additives or reducing agents. EDAC.HCl is transformed to the corresponding urea during coupling reactions, which has the advantage over DCU or DIC that it can removed from the reaction mixture by extraction or be washed out from solid phase synthesis applications. However, the O-acylisourea can rearrange irreversibly to an N-acylurea and also racemise the α-carbon of the amino acid via formation of an oxazol-4(5H)-one [azlactone]. N-Acylurea formation and racemisation may be reduced by using intermediate nucleophiles, which convert the O-acylurea to an activated ester containing the nucleophile.
EDAC coupling (without nucleophil additive) is illustrated in the figure below taken over from the literature.
Tautomer forms
EDC displays ring-chain tautomeric forms. The figure below shows one of ring-chain tautomeric forms.
The IR absorption spectrum in chloroform solution displays a band at 2130 cm-1 (-N=C=N-) which is indicative of the open chain form. However, KBr disc or Nujol dispersion of the solid has vmax values at 3250 and 1700 cm-1 that are characteristic of N-H and C=N bonds respectively which are derived from the cyclic tautomers in the crystal form of EDAC.HCl
FT-IR spectrum in KBr
EDC.HCl is superior to DCC and DIC with regards to its high solubility in water (>200 g/L) and also in organics like CH2Cl2, THF, DMF and its ease of use.
Heat stability – melting point
The behavior of EDAC.HCl (in solid form) sample was performed using a simultaneous thermoanalytical method using a NETZSCH STA 409 CD type device. The simultaneous examination consisted of a parallel thermogravimetric and differential scanning calorimetric measurement. These curves resulting from examination are introduced in one figure together in a typically case below.
As the heat flow curve shows an endoterm melting progress is followed by an exoterm decomposition which can be clearly determined from the weight loss visible on the TG curve. In addition, it can also be read from the figure that the onset of melting and thermal decomposition fall within a very narrow temperature range, in the case shown in the figure 114 0C and 117 0C respectively. For this reason, one may wonder how exothermic decomposition affects (apparently reduces) the value of the melting point. Thinking further, if we measure the melting point of an EDAC.HCl sample using the capillary method, can we be sure that the thaw of the substance in the capillary is the result of real melting or exothermic decomposition.