Page 265 - Chiral Separation Techniques

9.6 Operation of the SMB Unit 243

return to their initial positions. A three-head membrane pump (Milroyal) is used for the
recycling flow. This pump is fixed in the system, between the last and the first columns.
Consequently, depending also on the injection and collection lines positions, the recy-
cling pump can be, successively, in zone IV, III, II or I, and its flow rate must be set
accordingly. Following the same notation used in the previous chapters, we define the
recycling flow rate as the flow rate occurring in section IV.

9.6.1 Separation of Bi-Naphthol Enantiomers

The separation of bi-naphthol enantiomers can be performed using a Pirkle-type sta-
tionary phase, the 3,5-dinitrobenzoyl phenylglycine covalently bonded to silica gel.
Eight columns (105 mm length) were packed with particle diameter of 25–40 µm.
The solvent is a 72:28 (v/v) heptane : isopropanol mixture. The feed concentration
is 2.9 g L –1 for each enantiomer. The adsorption equilibrium isotherms were deter-
mined by the Separex group and already reported in Equation (28) [33].
The operating conditions used in a SMB configuration 2-2-2-2 at 25 °C recycling
–1
–1
–1
flow rate 35.38 mL min , feed 3.64 mL min , eluent 21.45 mL min , extract
–1
17.98 mL min –1 and raffinate 7.11 mL min . The internal concentration profiles
were measured using the 6-port valve of the Licosep SMB pilot to withdraw samples
from the system. The samples were collected at each half-time period, and after 40
full cycles of continuous operation. The experimental performance parameters were
determined by analysis of the extract and raffinate samples collected during the
whole cycle 40 (cyclic steady-state). The better purity performance was obtained for
*
a switch time interval of t = 2.87 min, corresponding to a solid flow rate in the TMB
–1
of 11.65 mL min . For this value, purities as high as 94.5 % in the extract and
98.9 % in the raffinate were obtained with good recoveries. A productivity of 68 g
of racemic mixture processed per day and per liter of bed was achieved. The corre-
–1
sponding solvent consumption, was 1.2 L g racemic mixture.
The steady state TMB model was used to simulate the SMB operation by pre-
dicting its performance and its internal concentration profiles. Model parameters are
the solid/fluid ratio (1–ε)/ε = 1.5, Pe = 2000 and α = 34.44 corresponding to
–1
k = 0.1 s . The ratio between fluid and solid velocities in the TMB are: γ = 6.31,
I
γ = 4.00, γ = 4.47, and γ = 3.55. The predicted extract purity is 95.2 %; for the
II III IV
raffinate the purity predicted is 99.1 %.
9.6.2 Separation of Chiral Epoxide Enantiomers

The second system studied was the separation of the chiral epoxide enantiomers
(1a,2,7,7a-tetrahydro-3-methoxynaphth-(2,3b)-oxirane; Sandoz Pharma) used as an
intermediate in the enantioselective synthesis of optically active drugs. The SMB has
been used to carry out this chiral separation [27, 34, 35]. The separation can be per-
formed using microcrystalline cellulose triacetate as stationary phase with an aver-
age particle diameter greater than 45 µm. The eluent used was pure methanol. A