MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©
2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
Tertiary Amines
731
room temperature and regenerated II. Filtration of the mixture gave
excessive I, VII and a solution of II and VIII in CH Cl . Separation of
II and VIII can be easily realized by precipitating II using icy-cold Et O.
2
2
2
Finally, VIII was obtained in 95–98% purity.
It is worth being mentioned that, in each step of the sequence, the
PEG-bound products were precipitated selectively and the excess low
molecular reagents and the by-products were removed by simple filtration
and were easily detected by TLC which was used to confirm the complete
removal of the reagent in excess and the soluble by-products, the PEG-
bound intermediates were easily analyzed to confirm the structure with
routine analytical methods (UV, IR, H NMR) without following cleave-
[
7]
&
-analyze technique or spectral analyze technique. During the course
[
8]
of preparing II and VIII, use of I as base and scavengers largely
simplified the purification procedure and facilitated spectral analysis of
the PEG-bound products and final products comparing with the reported
methods, in which polar trialkylamine hydrochloride or iodide was
difficult to be disposed of during reaction work-up. Addition of the
mixture of I and VII t o 1 M NaCO in water regenerated I which
2
3
can be reused. II recycled in Hofmann elimination reaction can also be
reused.
Table 1 shows the representative tertiary amines that have been
prepared by this route. The purity of the products is excellent, which
may be due to the fact that only the desired PEG-bound quaternized
amine VI was susceptible to the cleavage conditions by use of the
insoluble weak basic resin. The very low yields (21%, 23%) obtained
for two of the transformations in Table 1 were thought to be owing to
poor quaternization of ethyl bromide.
In conclusion, use of PEG as the soluble polymer support provided a
facile method for the synthesis of tertiary amines. Insoluble weak basic
resin simplified the purification. Further explorations for extending the
application of this method to the synthesis of focused libraries are being
developed and will be reported in due course.
EXPERIMENTAL
All organic solvents were dried by standard methods. All PEG
ꢀ
samples were melted at 80 C in vacuum for 30 min before use to remove
traces of moisture. After reaction, products were purified by evaporation
of the reaction solvent in vacuum, followed by addition of the residue
dissolved in a few of CH Cl t o EtO, stirred and cooled for 20–30 min
2
2
2