CRYSTAL AND MOLECULAR-STRUCTURE ANALYSIS OF FLUTAMIDE - BIFURCATED HELICOIDAL C-H ... O HYDROGEN-BONDS

Crystal structure determination and semiempirical AM1 and PM3 calculat ions were performed on flutamide {2-methyl-N[4 nitro-3-(trifluoromethy l) phenyl] propamide}, a powerful nonsteroidal androgen antagonist. Th e molecule is almost planar apart from CF3, NO2, and CH3 groups. The N O2 plane makes an angle of 36.3(4)degrees with the least-square plane of the phenyl ring. The molecules are intermolecularly linked by one N -H ... O and one C-H ... O hydrogen bonds. A bifurcated helicoidal hyd rogen bond network is formed by the intermolecular C-H ... O hydrogen bond together with another intramolecular C-H ... O hydrogen bond. The calculated structures are in good agreement with the crystallographic conformations. AMI is more accurate for predicting the intramolecular C-H ... O hydrogen bond while PM3 gives a better geometry for the cro wded nitro group. AM1 and PM3 charges of benzenic hydrogens are used t o predict the propensity of these atoms to form hydrogen bonds. The no ncentrosymmetric space group of the crystal (Pna2(1)), the calculated dipole moment (8.88 D), and the calculated angle between molecular dip oles and the twofold axis (approximately 49-degrees) close to the opti mal value (54.7-degrees) indicate that flutamide might be a possible c andidate for nonlinear optical material.