Predicting co-crystal structures of N-halide phthalimides with 3,5-dimethylpyridine

Area of Science:

• Solid-state chemistry
• Crystallography
• Computational chemistry

Background:

• Co-crystals are crystalline solids composed of two or more different molecules in a defined stoichiometric ratio.
• N-halide phthalimides and 3,5-dimethylpyridine are organic compounds with potential for intermolecular interactions.
• Understanding co-crystal formation is crucial for materials science and drug development.

Purpose of the Study:

• To investigate the potential for co-crystal formation between N-halide phthalimides (N-chlorophthalimide, N-bromophthalimide, N-iodophthalimide) and 3,5-dimethylpyridine using computational methods.
• To predict and analyze the resulting crystal structures and identify key intermolecular interactions.
• To assess the feasibility of co-crystal formation for different halogen substituents.

Main Methods:

• Crystal structure prediction (CSP) calculations were employed.
• Computational modeling was used to generate and rank potential co-crystal structures.
• Analysis of intermolecular interactions, particularly N-X...N bonds, was performed.
• Comparison with existing experimental data from the Cambridge Structural Database.

Main Results:

• The co-crystal structure of N-bromophthalimide (nbp) with 3,5-dimethylpyridine (35DMP) was successfully predicted and matched the known experimental structure (VELXES).
• A likely co-crystal structure was proposed for N-iodophthalimide (nip) with 35DMP.
• Co-crystal formation between N-chlorophthalimide (ncp) and 35DMP was predicted to be improbable.
• Strong N-X...N interactions were identified as a significant factor governing the stability and formation of these co-crystals.

Conclusions:

• Computational crystal structure prediction is a viable method for exploring co-crystal formation.
• The presence and strength of N-X...N interactions are critical determinants for the successful formation of N-halide phthalimide-35DMP co-crystals.
• Co-crystal formation is dependent on the specific halogen substituent, with bromo and iodo derivatives showing higher propensity than chloro derivatives.