- Email: [email protected]
Synthesis of the first truly reactive polymer-bound NADH models
Tetrahedron Letters Vol. 22, pp 59 - 60 @Pergamon Press Ltd. 1961. Printed in Great
SYNTHESIS
OF THF FIRST TRULY REACTIVE
By R. Mathis, Laboratoire 1'Institut Aignan,
de Chimie Organique National
Britain
Supdrieur
POLYMSR-BOUND
G. Dupas, A. Decormeille
Hetdrocyclique
de Chimie
et G. Qudguiner*
de 1'Institut
Industrielle
NADH M3DELS
Scientifique
de Rouen, I.U.T.,
de Haute-Normandie,
de
B.P. 47, 76130 Mont Saint
France.
: Improved reduction of benzaldchydcs
Abstract
has been obtained
with reactive
polymer-
bound NADH models More than a hundred publications terature
with NADH model reactions
of the five last years. NADH model reactions
order to throw light on the biochemical functions
have been proved
The major difficulties chromatographic
Indeed, partially in acetonitrile
chloromethyl pyridinium
halogenomethylated pyridines
was quaternarized
functions,
Ib-g contained
to immobilize
Nevertheless,
little effort ha%:
easy to use in organic
of the reduction
products
synthesis.
which requires
usually
would be best solved if the NADH models
copolymers to produce
with polymers
to yield polymers
rings. Polymers
appears possible
by dihydropyridines.
in
number of organic
polymers.
with 3-substituted
Nicotinamide
have been studied up to now essentially
We felt that this problem
on insoluble
are found in the lit-
At the same time a growing
salts/dihydropyridines
come from the separation
techniques,
could be immobilized
mechanism.
to be reducible
been made to obtain reactive pyridiniwn
thylated
dealing
containing
Ia containing an average
all the pyridines
of styrene
and divinylbenzene
polymer-bound
NAD+ analogues
0.61,
respectively
of 1.1 mmole/g
reacted
Ia-g.
1.49 and 3.07 mole/g
0.39,
1.46 and 2.59 mmole/g
pyridinium
salts. Thus,
it
used up to now in NAD models on our halogenome-
copolymers. Due to their hydrophobic
features,
polymers
I were not easy to reduce by the usual
dithionite method'. On the other hand, it is known that the borohydride reduction of NAD+ gives 2 a mixture of the 1.2, 1.4 and 1-G isomers of NADH which has only half of the activity of true NADH3. However NaBH4 reduction than 0,5 % chlorine bound NAD+ models
of polymer
on microanalysis
could be readily
and appear to be even more reactive By reducing of polymer
Ia yielded
a yellow polymer
and showed to be a promising reduced
IIa which contained
reducing
in the same way. They are presently
than polymer
under investigation
110.
for Gl h in a sealed tube 1 mmole of m-nitrobenzaldehyde
IIa and 1,13 mmole of &1(Cl04)~~
less
reagent. All the other
in a l/l mixture
of anhydrous
with
lg (1,3 mmole)
acetonitrile
and benzene,
a 75 % yield of m-nitrobenzyl of the solvent). of substituted
Ohnishi
alcohol was obtained. (NMR determined after filtration and removal 5 et al. , who had obtained the highest yields published for the reduction
benzaldehydes
by NADH models,
"free" NADH model used in a lo-fold excess
reported
for the same reduction
a yield as low as 29 6.
59
by the corresponding
60
Ia-g Ia-f :X=Cl;
6 Z = CONRlR2 ; Ia amino, Ib dimethylamino, Ic diethylamino, Id pyrrolidino,
Ie piperidino, If morpholino. Ig : X = I ; Z = morpholinosulfonyl. Moreover, pure p and m-nitrobenzyl alcohol and p-chlorobenzyl alcohol were obtained easily by increasing the reaction time or the polymer/substratratio. Thus the polymer-bound NADH models are effective reducing reagents. We plan of course to explore the various features of these systems, such as selectivity and stereoselectivity. Kinetic features of our system are also currently under.study.
References and footnotes. 1) Quantitative dithionite reduction could be recently achieved. The first experiments show that
the dithionite reduced polymers give slightly better reduction yields than the corresponding NaBH4 reduced polymers. Dithionite reduction was achieved according to P.H. Westheimer et al. (J. Amer. Chem. Sot., 11, 2261 (1955)). 2) S. Chaykin, Ann. Rev. Biochem., 36, 149 (1967). 3) M.B. Mathews and E.E. Conn, J. Amer. Chem. Sot., 75, 5428 (1955). 4) No reduction occured without Mg(C104j2. 5)
Y.
Ohnishi and
M.
Kitami, Tetrahedron Letters, 4033 (1978).
6) A.S. Lindsey et al. (Polymer,1, 479 (1966)), Y. Kurusu et al. (Kogyo Kagaku Zasshi, 2,
934
(1968)), S. Shinkai et al. (Bull. Chem. Sot. Jap., 1918 (1975)) and U.K. Pandit et al. (Rec. Trav. Chim. Pays-Bas, )6, 215 (1977)) synthesised analogous polymers but only dyes and some other highly reducible molecules were reduced with these polymers (after reduction of the latter). In any caszthe efficiency of the polymer-bound NADH model was lower than that of N-benzyl-1,4 dihydronicotinamide.
(Receivedin France 18 July 1980)
SYNTHESIS
OF THF FIRST TRULY REACTIVE
By R. Mathis, Laboratoire 1'Institut Aignan,
de Chimie Organique National
Britain
Supdrieur
POLYMSR-BOUND
G. Dupas, A. Decormeille
Hetdrocyclique
de Chimie
et G. Qudguiner*
de 1'Institut
Industrielle
NADH M3DELS
Scientifique
de Rouen, I.U.T.,
de Haute-Normandie,
de
B.P. 47, 76130 Mont Saint
France.
: Improved reduction of benzaldchydcs
Abstract
has been obtained
with reactive
polymer-
bound NADH models More than a hundred publications terature
with NADH model reactions
of the five last years. NADH model reactions
order to throw light on the biochemical functions
have been proved
The major difficulties chromatographic
Indeed, partially in acetonitrile
chloromethyl pyridinium
halogenomethylated pyridines
was quaternarized
functions,
Ib-g contained
to immobilize
Nevertheless,
little effort ha%:
easy to use in organic
of the reduction
products
synthesis.
which requires
usually
would be best solved if the NADH models
copolymers to produce
with polymers
to yield polymers
rings. Polymers
appears possible
by dihydropyridines.
in
number of organic
polymers.
with 3-substituted
Nicotinamide
have been studied up to now essentially
We felt that this problem
on insoluble
are found in the lit-
At the same time a growing
salts/dihydropyridines
come from the separation
techniques,
could be immobilized
mechanism.
to be reducible
been made to obtain reactive pyridiniwn
thylated
dealing
containing
Ia containing an average
all the pyridines
of styrene
and divinylbenzene
polymer-bound
NAD+ analogues
0.61,
respectively
of 1.1 mmole/g
reacted
Ia-g.
1.49 and 3.07 mole/g
0.39,
1.46 and 2.59 mmole/g
pyridinium
salts. Thus,
it
used up to now in NAD models on our halogenome-
copolymers. Due to their hydrophobic
features,
polymers
I were not easy to reduce by the usual
dithionite method'. On the other hand, it is known that the borohydride reduction of NAD+ gives 2 a mixture of the 1.2, 1.4 and 1-G isomers of NADH which has only half of the activity of true NADH3. However NaBH4 reduction than 0,5 % chlorine bound NAD+ models
of polymer
on microanalysis
could be readily
and appear to be even more reactive By reducing of polymer
Ia yielded
a yellow polymer
and showed to be a promising reduced
IIa which contained
reducing
in the same way. They are presently
than polymer
under investigation
110.
for Gl h in a sealed tube 1 mmole of m-nitrobenzaldehyde
IIa and 1,13 mmole of &1(Cl04)~~
less
reagent. All the other
in a l/l mixture
of anhydrous
with
lg (1,3 mmole)
acetonitrile
and benzene,
a 75 % yield of m-nitrobenzyl of the solvent). of substituted
Ohnishi
alcohol was obtained. (NMR determined after filtration and removal 5 et al. , who had obtained the highest yields published for the reduction
benzaldehydes
by NADH models,
"free" NADH model used in a lo-fold excess
reported
for the same reduction
a yield as low as 29 6.
59
by the corresponding
60
Ia-g Ia-f :X=Cl;
6 Z = CONRlR2 ; Ia amino, Ib dimethylamino, Ic diethylamino, Id pyrrolidino,
Ie piperidino, If morpholino. Ig : X = I ; Z = morpholinosulfonyl. Moreover, pure p and m-nitrobenzyl alcohol and p-chlorobenzyl alcohol were obtained easily by increasing the reaction time or the polymer/substratratio. Thus the polymer-bound NADH models are effective reducing reagents. We plan of course to explore the various features of these systems, such as selectivity and stereoselectivity. Kinetic features of our system are also currently under.study.
References and footnotes. 1) Quantitative dithionite reduction could be recently achieved. The first experiments show that
the dithionite reduced polymers give slightly better reduction yields than the corresponding NaBH4 reduced polymers. Dithionite reduction was achieved according to P.H. Westheimer et al. (J. Amer. Chem. Sot., 11, 2261 (1955)). 2) S. Chaykin, Ann. Rev. Biochem., 36, 149 (1967). 3) M.B. Mathews and E.E. Conn, J. Amer. Chem. Sot., 75, 5428 (1955). 4) No reduction occured without Mg(C104j2. 5)
Y.
Ohnishi and
M.
Kitami, Tetrahedron Letters, 4033 (1978).
6) A.S. Lindsey et al. (Polymer,1, 479 (1966)), Y. Kurusu et al. (Kogyo Kagaku Zasshi, 2,
934
(1968)), S. Shinkai et al. (Bull. Chem. Sot. Jap., 1918 (1975)) and U.K. Pandit et al. (Rec. Trav. Chim. Pays-Bas, )6, 215 (1977)) synthesised analogous polymers but only dyes and some other highly reducible molecules were reduced with these polymers (after reduction of the latter). In any caszthe efficiency of the polymer-bound NADH model was lower than that of N-benzyl-1,4 dihydronicotinamide.
(Receivedin France 18 July 1980)