Synthesis of phosphonates in a continuous flow manner

Article abstract of DOI:10.1080/10426507.2018.1528253

The synthesis of dialkyl H-phosphonates and α-aminophosphonates was studied in a continuous flow microwave reactor. Depending on the conditions, the alcoholysis of dialkyl H-phosphonates could be fine-tuned towards the mixed and the fully transesterified products. The continuous flow synthesis of α-aryl-α-aminophosphonates was elaborated utilizing the aza-Pudovik reaction of imines and dialkyl H-phosphonates, as well as the by the Kabachnik-Fields condensation of primary amines, benzaldehyde and > P(O)H reagents.

Full text of DOI:10.1080/10426507.2018.1528253

Phosphorus, Sulfur, and Silicon and the Related Elements
ISSN: 1042-6507 (Print) 1563-5325 (Online) Journal homepage: https://tandfonline.com/loi/gpss20
Synthesis of phosphonates in a continuous flow
manner
Nóra Tóth, Ádám Tajti, Katalin Ladányi-Pára, Erika Bálint & György Keglevich
To cite this article: Nóra Tóth, Ádám Tajti, Katalin Ladányi-Pára, Erika Bálint & György Keglevich
(2019): Synthesis of phosphonates in a continuous flow manner, Phosphorus, Sulfur, and Silicon
and the Related Elements, DOI: 10.1080/10426507.2018.1528253
To link to this article: https://doi.org/10.1080/10426507.2018.1528253
Published online: 01 Mar 2019.
Submit your article to this journal
View Crossmark data
Full Terms & Conditions of access and use can be found at
https://tandfonline.com/action/journalInformation?journalCode=gpss20

PHOSPHORUS, SULFUR, AND SILICON AND THE RELATED ELEMENTS
https://doi.org/10.1080/10426507.2018.1528253
Synthesis of phosphonates in a continuous flow manner
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
€
Nora Toth, Adam Tajti, Katalin Ladanyi-Para, Erika Balint , and Gyorgy Keglevich
Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, Budapest, Hungary
ABSTRACT
ARTICLE HISTORY
Received 9 May 2018
Accepted 21 September 2018
The synthesis of dialkyl H-phosphonates and a-aminophosphonates was studied in a continuous
flow microwave reactor. Depending on the conditions, the alcoholysis of dialkyl H-phosphonates
could be fine-tuned towards the mixed and the fully transesterified products. The continuous flow
synthesis of a-aryl-a-aminophosphonates was elaborated utilizing the aza-Pudovik reaction of
imines and dialkyl H-phosphonates, as well as the by the Kabachnik-Fields condensation of pri-
mary amines, benzaldehyde and> P(O)H reagents.
KEYWORDS
Dialkyl H-phosphonates;
a-aminophosphonates;
alcoholysis; Kabachnik-Fields
reaction; Pudovik reaction;
continuous flow reactor
GRAPHICAL ABSTRACT
Microwave (MW)-assistance is a useful technique, however,
An efficient method has been developed for the synthe-
the size of the reactor is rather limited.[1] MW-assisted reac- sis of a-aryl-a-aminophosphonates (4) by the catalyst- and
tions on a bigger scale may be carried out in a continuous solvent-free MW-assisted aza-Pudovik reaction in a batch
flow MW equipment.[2] In this work, the synthesis of phos- MW reactor.[4] To make the procedure flow compatible, a
phonates was investigated in a self-developed continuous flow preliminary experiment was carried out for the addition
MW system based on a CEM Discover MW reactor equipped of diethyl phosphite to N-benzylidene(n-butyl)amine in
with a commercially available CEM continuous flow cell.
ethanol as the solvent (Scheme 2). The diethyl (n-butyla-
The continuous flow alcoholysis of dimethyl H- mino)-phenylmethylphosphonate
phosphonate (1) with n-butanol (Scheme 1) was studied in selectively.
(4)
was
formed
the single pump system based on our experiences in a
As an extension, after changing for a dual pump system,
batch MW reactor.[3] At a residence time of 30 min and at the same a-aminophosphonate (4) was prepared by the
100 ꢀC, the n-butyl methyl H-phosphonate (2) was three-component Kabachnik-Fields reaction of n-butylamine,
obtained in 53%, while at 175 ꢀC, the di(n-butyl) H- diethyl phosphite and benzaldehyde in ethanol without any
phosphonate (3) predominated (91%). Further increase of catalyst (Scheme 3). Although, the aldehyde and the phos-
the temperature did not change the composition.
phite were pumped form separated vessels 25% of the
Scheme 1. Continuous flow alcoholysis of dimethyl H-phosphonate with n-butanol.
ꢀ
€
CONTACT Erika Balint
ebalint@mail.bme.hu; Gyorgy Keglevich
gkeglevich@mail.bme.hu
ß 2019 Taylor & Francis Group, LLC

ꢀ
N. TOTH ET AL.
2
Scheme 2. Continuous flow synthesis of diethyl (n-butylamino)-phenylmethylphosphonate by aza-Pudovik reaction.
Scheme 3. Continuous flow reaction of n-butylamine, diethyl phosphite and benzaldehyde.
a-hydroxyphosphonate (5) was also formed beside the
desired product (4) (75%).
References
ꢀ
[1] Balint, E.; Keglevich, G. The Spread of the Application of the
Microwave Technique in Organic Synthesis, In: Keglevich, G.
(ed.) Milestones in Microwave Chemistry, Springer: Switzerland,
2016; pp 1–10.
Funding
The project was supported by the Hungarian Research Development
and Innovation Fund (FK123961 and K119202), the National Research,
Development and Innovation Fund of Hungary in the frame of
FIEK_16-1-2016-0007 (Higher Education and Industrial Cooperation
Center) project, and in part (E.B.) by the Jꢀanos Bolyai Research
Scholarship of the Hungarian Academy of Sciences.
[2] Kappe, C. O.; Stadler, A.; Dallinger, D. Microwaves in Organic
and Medicinal Chemistry, Wiley: Weinheim, 2012.
ꢀ
[3] Bꢀalint, E.; Tajti, A.; Drahos, L.; Ilia, G.; Keglevich, G.
Alcoholysis of Dialkyl Phosphites under Microwave Conditions.
Curr. Org. Chem. 2013, 17, 555–562.
ꢀ
ꢀ
[4] Bꢀalint, E.; Tajti, A.; Adꢀam, A.; Csontos, I.; Karaghiosoff, K.;
ꢀ
ꢀ
Czugler, M.; Abranyi-Balogh, P.; Keglevich, G. The Synthesis of
a-Aryl-a-Aminophosphonates and a-Aryl-a-Aminophosphine
Oxides by the Microwave-Assisted Pudovik Reaction. Beilstein
J. Org. Chem. 2017, 13, 76–86.
ORCID
ꢀ
Erika Balint
http:\\orcid.org\0000-0002-5107-7089