2 research outputs found
Demonstrating the Influence of Solvent Choice and Crystallization Conditions on Phenacetin Crystal Habit and Particle Size Distribution
Phenacetin was used as a model pharmaceutical
compound to investigate
the impact of solvent choice and crystallization conditions on the
crystal habit and size distribution of the final crystallized product.
The crystal habit of phenacetin was explored using crash-cooling crystallization
(kinetically controlled) and slow evaporative crystallization (thermodynamically
controlled) in a wide range of organic solvents. In general, a variety
of needle-type shapes (needles, rods, or blades) were recovered from
fast-cooling crystallizations, in contrast to hexagonal blocks obtained
from slow evaporative crystallizations. The solubility of phenacetin
was measured in five solvents from 10–70 °C to allow for
the design of larger-scale crystallization experiments. Supersaturation
and the nucleation temperature were independently controlled in isothermal
desupersaturation experiments to investigate the impact of each on
crystal habit and size. The crystal size (needle cross-sectional area)
decreased with increasing supersaturation because of higher nucleation
rates at higher supersaturation, and elongated needles were recovered.
Increasing the nucleation temperature resulted in the production of
larger crystals with decreased needle aspect ratios. Antisolvent phenacetin
crystallizations were developed for three solvent/antisolvent systems
using four different antisolvent addition rates to simultaneously
probe the crystal habit and size of the final product. In general,
increasing the antisolvent addition rate, associated with increased
rate of generation of supersaturation, resulted in the production
of shorter needle crystals
Exploring the Scope of Asymmetric Synthesis of β‑Hydroxy-γ-lactams via Noyori-type Reductions
Enantio- and diastereoselective
hydrogenation of β-keto-γ-lactams
with a ruthenium–BINAP catalyst, involving dynamic kinetic
resolution, has been employed to provide a general, asymmetric approach
to β-hydroxy-γ-lactams, a structural motif common to several
bioactive compounds. Full conversion to the desired β-hydroxy-γ-lactams
was achieved with high diastereoselectivity (up to >98% de) by
addition
of catalytic HCl and LiCl, while β-branching of the ketone substituent
demonstrated a pronounced effect on the modest to excellent enantioselectivity
(up to 97% ee) obtained