Ϫ1
21
ing to loading of 1.40 mmol g . The beads absorbed 8.4 times
their own weight of toluene.
before. This indicated that the chemical yield of 1-phenyl-
propanol was 95% and that benzyl alcohol was formed in 5%
yield. Toluene was also present. The crude 1-phenylpropanol
was purified by bulb-to-bulb fractional distillation in a
Preparation of polymer-supported catalysts
Kügelrohr apparatus. The major fraction (1.4 g) collected at
05 ЊC/0.1 mmHg was pure by GC and H NMR spectroscopy.
This fraction had [α]D ϩ42.7 (c = 5.0, CHCl ) (lit, [α]D
ϩ45.45 (c = 5.15, CHCl ) for the R-enantiomer) corresponding
21
Catalysts A and B were available from a previous study. The
beads were 100–200 mesh.
Catalysts C and D were prepared by reacting the chloro-
methylated polystyrene beads whose preparations are described
above with (1S,2R)- or (1R,2S)-ephedrine as appropriate using
the procedure given previously for the preparation of Catalyst
A. Catalyst C had, by elemental analysis, N 1.55% corre-
sponding to 1.11 mmol g of residues 4. Catalyst D had N
.71% corresponding to 1.22 mmol g of residues 2. The beads
1
1
20
39
20
3
3
to an ee of 94%. In the present case, in addition the Mosher
40
1
esters were prepared and the % ee determined by H and by
19
F NMR spectroscopy. The R- and S-enantiomers had signals
at δ 5.91 and 5.83 ppm respectively in the H NMR spectrum
and at δ Ϫ72.88 and Ϫ73.20 ppm respectively in the F NMR
spectrum in a ratio corresponding to an ee of 96%.
For the subsequent run the reagent reservoirs were simply
recharged and the pumps restarted. In some cases in addition to
determining the % ee by polarimetry, it was also determined
by GC analysis using a capillary column at 115 ЊC packed
with WT COT Fus Sil possessing the chiral species cyclo-
dextrin-β-2,3,6-M-19. With 1-phenylpropanol, for example,
the R- and S-enantiomers eluted after 35.5 and 36.8 minutes
respectively.
21
1
Ϫ1
19
Ϫ1
1
were 70–120 mesh.
Continuous flow apparatus and general details of the reaction
procedure
The general arrangement of the various flow apparatuses is
shown in Fig. 1. The flow tubes were made in house from com-
mercial Quickfit B14 joints and standard Pyrex glass tubing
by the departmental glassblower. In the Mark I and II appar-
atuses the glass sinters in the sidearms were of No. 3 porosity.
The dimensions of the tubes were as given in the caption to
Fig. 1.
21
TM
Recovery of catalyst ‘B’ from flow apparatus: re-use in batch
reactions
The setting up of the Mark III apparatus is typical. Thus, the
PS catalyst B (10.3 g), pre-swollen in toluene (50 ml), was trans-
ferred into the flow tube with the aid of a glass powder funnel.
The tube was then sealed with a standard ‘B14’ rubber septum
and placed in a water bath held at 20 ЊC by a Techne TU16A
After the 16th run summarised in Table 4, entry 11, the poly-
mer beads were quenched with methanol and transferred to a
Buchner filter. They were washed successively with methanol,
1
M hydrochloric acid-methanol (1:1), water, 10% triethyl-
amine in methanol, THF–methanol (1:1), THF, diethyl ether
and dried (10.2 g). The beads had an infrared spectrum indis-
tinguishable from the original: for example, there was no clear
carbonyl band. By elemental analysis they contained 0.57 mmol
of N per g.
Tempunit Thermoregulator. Hypodermic needles (19G, 24 in)
(
purchased from Aldrich) were inserted through the septum so
as to reach to the bottom of the tube. Initially, to allow the bed
to settle, toluene was pumped through the tube by two Watson-
Marlow 503U peristaltic pumps equipped with 501RL and
The recovered beads were used to catalyse batch reactions
3
03D/A pumpheads (these were subsequently used for the
21
following the previously described procedures. These reac-
diethylzinc and aldehyde reservoirs respectively) using Viton
0.8 mm ID) tubing. The reagent reservoirs were standard
round-bottomed flasks (each 500 ml; B24 joints) equipped with
B24’ rubber septa. The final reaction solution was extracted
tions and the results obtained are summarised in Table 5.
(
‘
Acknowledgements
We thank the EPSRC for financial support and Zeneca
from the reactor using another hypodermic needle (18G, 10 in)
placed ~0.5 cm above the bead bed and a Watson-Marlow
(
Blackley) for CASE Awards for D. W. L. S and P. W. S.
5
01U peristaltic pump equipped with a 501RL pumphead and
Viton tubing (1.6 mm ID). The receiver was a round-bottomed
flask (500 ml; B24 joint), equipped with a rubber septum, con-
taining a stirred mixture of toluene and 1 M aqueous hydro-
chloric acid. Flow rates for each pump were determined at each
control setting by measuring the volume of toluene pumped in
a given period of time. Since diethylzinc is pyrophoric at all times
the column, reservoirs and the receiver were kept under a dry
nitrogen atmosphere. This was achieved by having a series of
gas lines, branching from one source, with the nitrogen intro-
duced into the various pieces of the apparatus via small syringe
needles inserted through the rubber septa. The system was
vented via a similar set of needles and gas lines.
References
1
2
R. B. Merrifield, J. Am. Chem. Soc., 1963, 85, 2149.
Polymer-supported Reactions in Organic Synthesis, ed. P. Hodge and
D. C. Sherrington, John Wiley, Chichester, 1980.
Polymeric Reagents and Catalysts, ed. W. T. Ford, ACS Symposium
Series 308, Washington, 1986.
3
4 Syntheses and Separations Using Functional Polymers, ed. D. C.
Sherrington and P. Hodge, John Wiley, Chichester, 1988.
A. Akelah and A. Moet, Functionalised Polymers and Their
Applications, Chapman and Hall, London, 1990.
5
6
7
8
A. Akelah and D. C. Sherrington, Chem. Rev., 1981, 81, 557.
A. Akelah and D. C. Sherrington, Polymer, 1983, 24, 1369.
P. Hodge, Annu. Rep. Prog. Chem., Sect. B, Org. Chem., 1986, 83,
2
83–302.
Typical reaction procedure; run 1 in Table 4
9
P. Hodge, Chem. Soc. Rev., 1997, 26, 417.
A solution of freshly distilled benzaldehyde (8.5 g) in dry tolu-
ene (400 ml) was placed in one reagent reservoir. Diethylzinc
10 P. Hodge in Innovation and Perspectives in Solid Phase Synthesis, ed.
R. Epton, SPCC (UK) Ltd., Birmingham, 1990, pp. 273–292.
1
1
1
1 S. Itsuno and J. M. J. Frechet, J. Org. Chem., 1987, 52, 4140.
2 K. Soai, S. Niwa and M. Watanabe, J. Org. Chem., 1988, 53, 927.
3 K. Soai, S. Niwa and M. Watanabe, J. Chem. Soc., Perkin Trans. 1,
(
20.5 ml, 24.7 g), purchased as the neat liquid from Aldrich, was
transferred via hypodermic syringes (GREAT CARE: diethylzinc
is pyrophoric!) into dry toluene (400 ml) in the second reservoir.
Both reactant solutions were then pumped, each at a rate of 6
1
989, 109.
14 K. Soai and M. Watanabe, J. Chem. Soc., Chem. Commun., 1990, 43.
15 S. Itsuno, Y. Sakurai, K. Ito, T. Maruyama, S. Nakahama and
J. M. J. Frechet, J. Org. Chem., 1990, 55, 304.
Ϫ1
ml h , into the flow tube for 17 h at 20 ЊC. At the end of this
period the pumps were simply switched off and the toluene
layer collected from the receiver, washed with water (3 × equal
volume) and dried. The solvent was then carefully removed
using a rotary evaporator. The crude product (2.9 g) was
1
6 M. Watanabe, S. Araki, Y. Butsugan and M. Uemura, Chem.
Express, 1990, 5, 761.
1
1
7 Z. Zhang, P. Hodge and P. W. Stratford, React. Polym., 1991, 15, 71.
8 U. Kragl and C. Dreisbach, Angew. Chem., Int. Ed. Engl., 1996, 35,
642.
1
analysed by GC and by H NMR spectroscopy as described
J. Chem. Soc., Perkin Trans. 1, 1999, 2335–2342
2341