Refinement of the crystal structure of codeine hydrobromide dihydrate, and establishment of the absolute configuration of the codeine molecule

Abstract

The structure of codeine hydrobromide dihydrate has been refined with the use of complete threedimensional intensity data, and the absolute configuration of the codeine molecule has been established on the basis of the anomalous scattering of Cu Ka radiation by the bromine atom.

Structure of codeine

“…The bond lengths and angles (Table 2) are the same as those reported for morphine (Bye, 1976), within experimental error. However, there are some differences between these and those reported for codeine hydrobromide dihydrate (Kartha et al, 1962) and other morphine derivatives. The different bond distances for C9-N (1.521 A) and C16-N (1.468 A) reported for codeine hydrobromide dihydrate (Kartha et al, 1962) were not found to be different in codeine, where they were 1.477 (7) and 1.479 (7)A respectively.…”

“…However, there are some differences between these and those reported for codeine hydrobromide dihydrate (Kartha et al, 1962) and other morphine derivatives. The different bond distances for C9-N (1.521 A) and C16-N (1.468 A) reported for codeine hydrobromide dihydrate (Kartha et al, 1962) were not found to be different in codeine, where they were 1.477 (7) and 1.479 (7)A respectively. There is no apparent chemical reason for these two bonds to be 1.367 (6) C6-C5 1.528 (7) OI-C18 1-418 (7) C6-O2 1.427 (7) C 12-C 13 1.500 (7) C9-N 1.477 (7) C13-C5…”

“…The crystal-structure determination of codeine (I) was undertaken to establish the atomic and thermal parameters for later use in the calculation of a standard X-ray diffraction pattern for use in forensicscience laboratories. The basic configuration of codeine was originally determined by the structural analysis of codeine hydrobromide dihydrate (Lindsey & Barnes, CODEINE 1955) and refined by Kartha, Ahmed & Barnes (1962). Table References were made in the codeine hydrobromide structure analysis (Kartha et al, 1962) Intensities were collected for 1962 independent reflections with a maximum h = 13, k = 23 and l = 25 [one octant, (sin0)/,;I,<0.816~ -1, MoKa] with the 0-20 technique; of these 1205 had F 2 > 2tr(F 2) and were regarded as observed.…”

“…The basic configuration of codeine was originally determined by the structural analysis of codeine hydrobromide dihydrate (Lindsey & Barnes, CODEINE 1955) and refined by Kartha, Ahmed & Barnes (1962). Table References were made in the codeine hydrobromide structure analysis (Kartha et al, 1962) Intensities were collected for 1962 independent reflections with a maximum h = 13, k = 23 and l = 25 [one octant, (sin0)/,;I,<0.816~ -1, MoKa] with the 0-20 technique; of these 1205 had F 2 > 2tr(F 2) and were regarded as observed. No absorption correction was applied because the measured intensities for three reflections only varied with path length through the crystal by an average of 2% when the crystal was systematically rotated around the diffraction vector (~ scans).…”

Structural studies of substituted 6,7-benzomorphan compounds. II. Absolute configurations of (−)-2-cyclobutylmethyl-5-ethyl-2'-hydroxy-9,9-dimethyl-6,7-benzomorphan hydrobromide (NCBME) and (−)-5-ethyl-2'-hydroxy-2,9,9-trimethyl-6,7-benzomorphan hydrobromide dihydrate (NME)

“…HCI. 3H20 (V) using the atomic numbering of NCBME (7) -1.5 (6) -2.4 (9) -1.4 (5) -3.7 (9) (7) -2.4 (7) 3.0 (9) 1.6 (5) 11.1 (11) (7) 2.4 (7) -1.9 (9) 0.0 (4) -I1.0 (15) (7) 1.3 (6) 0.1 (7) -1.9 (4) -1.0 (10) (6) -5.3 (6) 0.5 (8) -2.0 (4) 5.4 (10) hydrobromide dihydrate (Kartha, Ahmed & Barnes, 1962) where the bromide is solely bonded to the solvent molecules. In this crystal, the distances and angles between donor and acceptor atoms, defining the hydrogen-bonding system (Table 8), also represent acceptable values.…”