1,3-Diisopropylcarbodiimide
N,N'-Diisopropylcarbodiimide
CAS 693-13-0
General Information on 1,3-Diisopropylcarbodiimide (CAS 693-13-0)
N,N'-Diisopropylcarbodiimide (DIC) is a highly efficient coupling reagent extensively utilized in organic synthesis, particularly in the formation of amide bonds. Owing to its pronounced reactivity, it plays a critical role in peptide synthesis and various other condensation reactions. The compound’s structural features promote selective activation of carboxylic acids under mild conditions, thereby enhancing reaction yields while minimizing side product formation. These characteristics make it especially valuable in biochemical and pharmaceutical applications involving sensitive substrates.
In addition to amide formation, DIC is also widely applied in esterification and in activating carboxylic acids for further transformations. Its broad functional group compatibility and operational ease under ambient conditions expand its synthetic utility. Compared to alternative reagents, DIC often results in improved product purity and streamlined purification.
Applications in Peptide Chemistry and Amide Bond Formation
N,N'-Diisopropylcarbodiimide (CAS 693-13-0) serves as a reliable reagent in peptide bond formation and is utilized in the synthesis of protected peptides, N-hydroxysuccinimide (NHS) esters, N-acylureas, and 2-alkoxyoxazolones. It also supports dipeptide synthesis and has proven effective in a range of other condensation reactions.
Beyond peptide synthesis, DIC is applied in the preparation of N-silylformamides through hydrosilylation and in the formation of polyimide precursor coatings for use in electrophoretic display technologies. Its solid-supported form, in combination with auxiliary reagents, has enabled macrocyclization of cyclic peptides. Furthermore, DIC facilitates the synthesis of α,β-dehydroamino acid derivatives and serves as a stabilizing agent in various chemical systems.
Advantages of 1,3-Diisopropylcarbodiimide over N,N’-Dicyclohexylcarbodiimide
DIC is considered a more practical alternative to dicyclohexylcarbodiimide (DCC) in many synthetic applications. Although both reagents exhibit comparable coupling efficiencies, the byproduct formed during DIC-mediated reactions—diisopropylurea—is more soluble in organic solvents than the dicyclohexylurea generated by DCC, allowing for easier removal during purification. This is especially advantageous in solid-phase peptide synthesis (SPPS).
Additionally, as a liquid at room temperature, DIC is easier to handle and dispense than DCC, which is a low-melting-point crystalline solid. These features contribute to its widespread adoption in both research and industrial-scale synthesis.
Additional Synthetic Applications of 1,3-Diisopropylcarbodiimide
Beyond its role in peptide chemistry, N,N'-Diisopropylcarbodiimide has been employed in a variety of organic transformations. It is used in cycloaddition reactions to generate heterocyclic compounds and in dehydration processes for the synthesis of conjugated alkadienoic acids and anhydrides.
In polymer synthesis, DIC catalyzes the production of polyesters from hydroxyphenyl-terminated carboxylic acids in the presence of specific catalysts. It is also utilized as a stabilizer in chemical formulations requiring enhanced storage properties, including certain defense-related compounds.
Conclusion
1,3-Diisopropylcarbodiimide (CAS 693-13-0) represents a reliable, efficient, and versatile coupling agent suitable for a wide array of organic transformations. When directly compared to N,N’-Dicyclohexylcarbodiimide, 1,3-Diisopropylcarbodiimide consistently demonstrates superior handling, solubility, and purification characteristics. Its continued adoption in both academic and industrial environments confirms its status as a reagent of choice in contemporary synthetic chemistry.