Analysis of weak interactions involving fluorine: a comparative study of crystal packing of some benzodiazepinone drug intermediates and their non-fluorinated analogues

Weak interactions involving fluorine have been analyzed in terms of altered packing modes in the crystalline lattice in four benzodiazepinone drug intermediates which are determined by X-ray diffraction. Two of them are non-fluorinated and the other two are corresponding mono-fluorosubstituted derivatives. The compounds are 2-chloroacetamido-5-chlorobenzophenone (C15H11Cl2NO), 2-chloroacetamido-5-chloro-2'-fluorobenzophenone (C15H10Cl2FNO2), 7-chloro-1,3-dihydro-5-phenyl- 2H-1,4-benzadiazapin-2-one (C15H12ClN2O) and 7-chloro-1,3-dihydro-5-(2'-fluorophenyl)-2H-1,4-benzadiazapin-2-one (C15H11ClN2OF). The conformational features in the first two compounds are essentially governed by strong intramolecular interactions. Specific C-H center dot center dot center dot F intermolecular interactions along with C-H center dot center dot center dot pi interactions generate altered packing modes in fluorinated intermediates. The latter two compounds have strong N-H center dot center dot center dot O intermolecular hydrogen bonds as well.