2

NATIONAL CONFERENCE ON MATERIALS,ENERGY& ENVIRONMENT

nd

FEBRUARY,13-14,2024
Ultrasound Assisted Green Synthesis of α-Hydroxyphosphonates with Zn(OAc) 2 as a
Catalyst

Rayene SAYAD*1, Zineb AOUF1, Abdselem BOUZINA 1, Nour-Eddine AOUF 1 .

1
Laboratory of Applied Organic Chemistry, Bioorganic Chemistry, Badji Mokhtar-Annaba University, Faculty of Sciences, Department of Chemistry,
Box 12, 23000 Annaba, Algeria
*
Corresponding Author email: rayenesayad99@gmail.com

Abs t r ac t
A new and effective method has been developed for the synthesis of α-Hydroxyphosphonates via Pudovic reaction was reported in this work, by the combination of aromatic
aldehyde and diethylphosphite under Ultrasound irradiation with Zn(OAc)2 as catalyst allow the desired product to be obtained with a high yield. The spectroscopic methods
(1H NMR and IR) were used to determine the structural characteristics of the synthesized compounds
Key words: α-hydroxyphosphonates, Pudovic reaction, Us irradiation, Zn(OAc) 2, Green synthesis .

Background  Spectral Study :

The structure of obtained compound, was confirmed by usual spectroscopic
Organophosphorus compounds are experiencing a surge in applications due to their methods.
diverse biological activities, particularly in the pharmaceutical industries [1].  The infrared spectra exhibited characteristic signals for the OH group (3261
Specifically, their P-C bond formation reactions are key in producing these valuable cm-1), the phosphonate (P=O, 1225 cm-1 and 1075 cm-1 cm-1) groups.
molecules. One important class within this realm is α-hydroxyphosphonates, exhibiting  In the 1H-NMR spectra, the P-CH gave a doublet 4.99 ppm and the OH proton
anticancer (1) antioxidant(2), and pesticide (3) properties [2]. Pudovik and Abramov appeared as a broad singlet at 5 ppm. The two triplets at 1.22 ppm attributed
reactions represent the most well-known methods for the preparation of α- to the ethoxy groups of the phosphonate moiety as well as the multiplets
Hydroxyphosphonates under various reaction conditions [3]. integrating for the two methylene groups of the phosphonate at 4.07 ppm
OH OH
Cl
OEt
Cl
OEt confirmed the formation of the targeted compound.
P P O O
OEt OEt H
O O P N
OH OH HO OH
Cl (1) OH
(2) (3)

Figure 1. Anticancer, antioxidant, and pesticide properties of α-hydroxyphosphonates.

EtO
Additionally, combining ultrasound with catalytic systems (sonocatalysis) is a powerful HO P
O

new approach that boosts chemical reactions, this "synergy" is beneficial in many fields OEt

like organic synthesis and pharmaceuticals resarch. Sonocatalysis offers several

advantages: faster reactions, improved transfer, higher yields and selectivity [4].

In this context, our focus is on synthesizing α-hydroxyphosphonates through the Pudovic

reaction, employing ultrasound/Zn(OAc)2 as a sonocatalysis system.

Results and
Discussion .

The process involves the condensation of different structure of aromatics aldehydes

(4) (1 mmol) and diethylphosphite (5) (1.2 mmol) via pudovik reaction, in de presence of
EtO
O
10% of Zn(OAc)2 in 10 mL of EtOH, as a green solvent, under sonication (40 kHz, 60°C) HO P
OEt
for 15 minutes as shown in scheme 1. Upon completion of the reaction, Zn(OAc)2 was
precipitated and then filtered. Subsequently, the reaction mixture was concentrated by
vacuum evaporation. To isolate the pure product, a mixture of diethyl ether and n-
hexane in a 6:4 ratio was added to the concentrated solution. The solution was then
subjected to overnight cooling at 6°C, leading to the crystallization of the desired
product. This procedure was conducted to synthesize and isolate
EtO
O
all compounds.
H O HO P
O 10% Zn(OAc)2/US (40 kHz, 60°C) OEt
+ EtO P OEt
R
R
H EtOH, 15min
(4) (5) (6) Figure 2: 1H NMR and IR spectrum of
R= H, 4-Cl, 4-F, 4-Br, 4-OMe
Yields =[90-94]% diethylhydroxyl(phenyl)méthylphosphonate

Scheme 1. Synthesis a-hydroxyphosphonates using ultrasound/Zn(OAc)2 as a

sonocatalysis system

References
Conclusion [1] M. Lee, E.Fong, Cancer. Res. 61 (2001) 2602.
[2] K. Naidu, K.Kumar, Arch. Pharm. 345 (2012) 957.
In summary, we present an effective approach, an environmentally friendly catalytic
[3] a) S. Chandrasekhar, C. Narsihmulu, S. S. Shameem, B. Saritha, S. J. Prakash,. Synlett;,
process, for the hydrophosphonylation of aldehydes using Zn(OAc)2. This method has 505. b) H. Takahashi, M. Yoshioka, N. Imai, K. Onimura, S. Kobayashi, Synthesis., 2003 (1994)
been achieved through the pudovik reaction under ultrasonic irradiation, demonstrating 763.

both efficiency and convenience. [4] I. Machado, J. dos Santos, Ultrason. Sonochem .78 (2021) 105704.