C-ONtemplate the power of alkoxyamine derivatives

Haykal Nour, Kasdi Nour el houda, Hamie Farah, Ben Sassi Myriam
HAC613C, Projets Tuteurés, Licence L3 Parcours SCV

1. INTRODUCTION
Alkoxyamines are intriguing molecules due to their possession of a nitroxide function, characterized by a thermosensitive covalent C-O bond that, upon
rupture, generates radicals. This property enables their application in diverse fields, including biomedicine and radical polymerization. Our project focuses on
synthesizing an organic derivative possessing an alkoxyamine function based on TEMPO (2,2,6,6-tetramethylpiperidine 1-oxyl) on one side and a phosphonic
acid function on the other side, allowing its attachment to nanoparticles. These nanoparticles are intended for treating olive trees and grapevines afflicted by
the bacterium "Xylella Fastidiosa." In this project, we discuss the experiments by zooming in on the formation of the C-O-N bond. Our synthesized
alkoxyamine derivative conjugated to iron oxides constitutes a system that can be activated by a controlled magnetic stimulus to release TEMPO radicals and
other species capable of initiating a cascade of temperature-controlled mechanisms, ultimately leading to targeted bacterial eradication.

2. SYNTHESIS AND RESULTS

STEP 2 STEP 3
It’s a saponification reaction through which we
endeavor to recover our carboxylic acid
functionality

Mechanism of the secondary Overnight at 30°C.

reaction Column chromatography (MeOH/CH 2Cl 2 1 /9).
Yield: 45%.
1H NMR (400MHz, CDCl ): The low height of the
3
peak corresponding to -CH3 indicates the
It’s a radical reaction involving the grafting of the TEMPO transformation of the ester function into an acid.
radical onto the double bond of our molecule. Collection of the
TLC of the reaction purification
Column chromatography (Et 2 O/EP 7/3).
Yield: 26%.
1 H NMR (400MHz, CDCl ): The analysis was conducted to
3
confirm the successful synthesis of the desired product.
TH K
The purity of the product is not fully validated. F/H OH
O 30 2O
MP ° CO (1:
1)
TE Cl 2 ve
n + Mn rn
s ali igh
t
t
d
an H 4 , r.
Lig NaB rOH ight
iP rn
STEP 1 Ov
e STEP 4 AND 5

EDCI
H 2N-NH 2 , EtOH DMAP
MeI DMSO, r.t DCM
r.t Overnight
K 2CO3 1h30min 0°C, r.t
It’s an Arbuzov reaction, the reaction of a trialkyl
phosphite with an alkyl halide to produce an alkyl
It’s a protection step : we protect our acid function by P(OEt) 3
Reflux, 5h phosphonate.
forming an ester.
Yield: 57%.
1 hour & 30 minutes at room temperature. 1 31
NMR H & P
Column chromatography (DCM/ethyl acetate
gradient from 0% to 5% of ethyl acetate).
Yield: 64%. CM
1 H NMR (400 MHz, CDCl ) : The analysis was r, D °C 31
SB P NMR (CDCl 3 , 121 MHz)
3 TM t o0
°C
conducted to confirm the successful synthesis of -20
the desired product, which is methyl 4-vinyl
benzoate.

Results :
Two peaks were detected at 32.14
ppm and 33.94 ppm.
One peak corresponds to our target
molecule 4A.
The second peak is attributed to
ethyl diethylphosphonate (a
secondary product from the
reaction between EtBr and P(OEt) 3 .
To prevent its formation, airflow
could have been introduced as ethyl
bromide is volatile.
The peak detected at 7.25 ppm is
attributed to P(OEt)3 .

1 H NMR (400 MHz, CDCl )

3
Results:
The presence of our product is highlighted by the peak of the -CH3 of our ester
function, which appeared at 3.81 ppm, and the disappearance of the acidic proton, It’s a Gabriel reaction that transforms an alkyl phthalimide to a primary amine
which appears at a much greater chemical shift. To do so:
Overnight at room temperature.
Column chromatography (CH 3 Cl/MeOH 95/5).

3. REFERENCES
[1] B. Bouvet, S.Sene, G. Félix, J. Havot, G. Audran, S. R. A.
Marque, J. Larionova and Y. Guari, Nanoscale, 2022, p 6-8.
[4],Thibaud Reyser,1,2 Tung H. To,3 Chinedu
4. C ONCLUSION
This project has proven to be rather satisfying in certain aspects as we have obtained the
Egwu,1,2 Lucie Paloque,1,2 Michel Nguyen,1
Alexandre Hamouy,1 Jean-Luc Stigliani,1 desired products and the manipulations have been conducted successfully. Despite
[2] Jeffrey Havot, Synthèse et Étude d’Alcoxyamines Inédites : encountering difficulties, particularly with the formation of the C-O bond and the manipulation
de la théranostique à l’activation par résonance plasmonique
Christian Bijani,1 Jean-Michel Augereau,1,2 and
Gérard Audran3, Development of new of the amine, our experimental yields aligned closely with theoretical yields. Moving forward,
2022, p 123-169.
alkoxyamines free radicals against the two this project lays a solid base for future advancements in the synthesis of alkoxyamines
[3] Julian Dao, Didier Benoit,Craig J.Hawker, A Versatile and major parasitic diseases malaria and derivatives and highlights the valuable aspects of scientific explorations regarding the
Efficient Synthesis of Alkoxyamine LFR Initiators via Manganese schistosomiasis, 2020, p 26-30. potential contributions of the synthetized products to diverse fields of chemistry.
Based Asymmetric Epoxidation Catalysts, 2000, p 2162-2167.