Solid phase chemistry at a modified cathode surface. First synthesis of a polyamine precursor

Article abstract of DOI:10.1016/S0040-4039(99)02217-0

The synthesis of a polyamine precursor was performed at a modified electrode interface. The chemical behaviour of the polythiophene matrix appeared identical to that of polystyrene beads. The target molecule, obtained with good yield, was released from the solid support by cathodic S-N bond scission, using the conducting properties of the polymer. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(99)02217-0

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 883–885
Solid phase chemistry at a modified cathode surface.
First synthesis of a polyamine precursor
∗
Gilles Marchand, Jean-François Pilard and Jacques Simonet
Laboratoire d’Electrochimie Moléculaire et Macromoléculaire, Université de Rennes I, Campus de Beaulieu, 35042 Rennes,
France
Received 8 November 1999; accepted 24 November 1999
Abstract
The synthesis of a polyamine precursor was performed at a modified electrode interface. The chemical behaviour
of the polythiophene matrix appeared identical to that of polystyrene beads. The target molecule, obtained with
good yield, was released from the solid support by cathodic S–N bond scission, using the conducting properties of
the polymer. © 2000 Elsevier Science Ltd. All rights reserved.
Keywords: polyamines; solid phase synthesis; polythiophene; modified cathode; electrochemical bond cleavage.
1
The possible use of functionalized polythiophenes in solid-phase chemistry has recently been describ-
ed. To validate this methodology, we have investigated the polyamine synthesis at modified electrode
2
interfaces. Apart from the biological aspect that makes polyamine derivatives of particular interest, the
3
build-up of such entities on a solid support is known to present numerous advantages, especially for their
purification. Moreover, the use of fast and highly selective S–N bond cleavages previously demonstrated
1
on a model polymer should indeed provide a good alternative to usual reactions implying polystyrene
beads.
The poly-[1] matrix, obtained from the corresponding monomer by electrodeposition on platinum
2
−1
+
plate (area=5 cm ) at constant potential (+1.40 V vs 0.1 mol L Ag /Ag electrode in CH CN, anodic
3
2
charge=2 C), was found to present an interfacial functionalization in the order of 2µmol/cm . This value
could be obtained, without any matrix structure change, either by direct or indirect means. The synthesis
4
of target molecule 2 was developed on this resin as shown in Scheme 1.
5
This three step sequence involved an azido amine condensation followed by the azido group
6
reduction and subsequent benzoyl choride condensation. Electrochemical cleavage led to the desired
7
product in 60% yield and 95% purity (NMR, MS and GC analysis). The progress of each step, performed
on a small area of the conducting polymer, was followed by FT-IR. Thus, a characteristic band centered at
−1
2
103 cm observed after 30 min reaction clearly demonstrated the azido amine condensation. Moreover,
∗
Corresponding author.
0
040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(99)02217-0
tetl 16145

8
84
−
Scheme 1. (i) H
2
+
N(CH
2
)
3
N
3
, pyridine; (ii) SnCl
2
, PhSH, Et
3
N, CH
3
CN; (iii) PhCOCl, Et
3
N, THF; (iv) 2e
E
red=−2.95 V vs
−1
−1
0
.1 mol.L Ag /Ag electrode in CH
3
CN containing 0.1 mol L Bu
4
NBF , cathodic charge=1.4 C, rt
4
a total azide band disappearance by treatment of the resin with tin dichloride was observed after only 5
min indicating total reduction. Finally, the acid chloride condensation, performed under dilute conditions
in order to avoid any by-products, was also followed by IR spectroscopy. Indeed, a strong band centered at
−1
1
652 cm does attest a successful conversion. Lastly, the chemical stability of this conducting polymer
was studied and compared with that of polystyrene beads. As expected, both matrixes present a similar
behaviour since no polythiophene denaturation was observed along the chemical elongation. Hence, the
conductivity of the recovered polymer was unchanged after each chemical step. The product release from
1
solid support was finally performed at room temperature according to a procedure already reported. This
8
9
electrochemical cleavage appeared to be faster (less than 1 min) than parent chemical or photochemical
processes. No effect on the target molecule was found owing to its low electroactivity.
In summary, a new solid phase methodology based on conducting modified electrode, has been
developed. Both attachment to and cleavage from this new polymeric support can be achieved under
milder and faster conditions than known procedures on polystyrene beads. It should therefore be
particularly useful for fragile compounds such as acid labile derivatives. Finally, regarding the small
amount of product synthesized at the cathode interface, this process seems to be of particular interest for
combinatorial synthesis where only a low quantity of compounds is required.
Acknowledgements
The authors wish to thank the University of Rennes 1 and CNRS for partial financial and technical
assistance. They are also very grateful to Electricité de France (EDF, DER Moret sur Loing) for the
interest in developing ‘solid phase electrochemistry’.
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