A novel bifunctional phosphoaminating agent, a process for the preparation thereof and the application thereof in the synthesis of aminophosphonates/aminophosphonic acids

Abstract

The present invention relates to a bifunctional phosphoaminating agent diethyl -(4,4-dimethyl-5-oxo-1,8,8-triphenyl-3,6-dioxa-2,7-diazaocta-1,7-dien-1-nyl)phosphonate of formula (E) and a process for the preparation thereof. Fig. 1

Specification

Description:FIELD OF THE INVENTION:
This invention relates to a novel bifunctional phosphoaminating agent, a process for the preparation thereof and the application thereof in the synthesis of aminophosphonates/aminophosphonic acids.

This invention further relates to a novel bifunctional phosphoaminating agent of formula (E), a process for the synthesis and characterization thereof and its application to the synthesis of aminophosphonates/aminophosphonic acids by reaction with various types of olefins via simultaneous generation of N- and P- centred radicals when subjected to visible-light mediated photocatalysis.

BACKGROUND OF THE INVENTION:
Traditionally, the construction of N- and P- containing molecules has been difficult, generally involving transition metals such as Mn, Cu, Ag, Co, etc. which makes these processes economically as well as environmentally, unfriendly. First isolation of amino phosphonic acid was discovered by Horiguchi and kandatsu in 1959 from the ciliate protozoa and the isolated compound was 2-aminoethylphosphonic acid. After that several reports were published on extraction of 2-aminoethylphosphonic acid from the living organism. The reports on aminophosphonate/aminophosphonic acid synthesis maybe classified into three categories:
1. C-C bond formation between two fragments already containing the amine and phosphonate functionalities respectively. The available reports on this strategy have been compiled in (Chemical Review, 2005, vol. 105, page 899-931).
2. The second strategy involves C-P bond formation between a phosphonate moiety and a prefunctionalized amine contatining carbon synthon. The available reports on this strategy have been compiled in (Chemical Review, 2005, vol. 105, page 899-931).
3. A third strategy relies on C-N bond formation between an amine moiety and a prefuncctionalized phosphonate containing carbon synthon, the reports having been compiled in (Chemical Review, 2005, vol. 105, page 899-931).
The plethora of these reported reactions were mainly carried out with the stoichiometric use of oxidant and bases, resulting in obnoxious side reaction and stoichiometric waste. Catalytic approach for the same grabs a substantial interest in recent times. Transition metal free phosphocarboxilation reaction was disclosed by Yu et al. (Nature Communication, 2019, vol. 11, page 3592) using hydrophosphine and vinyl amine derivatives which have selective functional possibility. γ-amino phosphonic acid, an important bioactive molecule was reported by Cresswell et al. (Tetrahedron, 2021, vol. 81, page 131896), introducing photocatalytic HAT strategy of primary and secondary amine to reaction with the vinyl phosphonate. In recent time Aggarwal et al. (Angewandte Chemie International Edition, 2022, vol. 61, e202207063) developed a decarboxylative strategy to transform the α-amino acid to amino phosphonic acid introduction trimethyl phosphite. A bifunctional strategy to access of the β-amino acid derivative was reported by Glorious et al. (Nature Chemistry, 2022, vol. 14, page 1174 - 1184) developing oxime ester derivative for both functionalization of amine and acid via photoredox catalysed energy transfer process. A single report was highlighted on the three component difunctional phospho-amination process via phosphonate radical generation followed by nucleophilic reaction of nitrile to get β-amino phosphonic acid synthesis was reported by Yang et al. (Chemical Communication, 2019, vol. 55, page 11888 - 11891). Glorious et al. first developed the bifunctional carbo-amination strategies (Angewandte Chemie International Edition. 2020, vol. 59, page 3172-3177) into the photoredox catalysis process, showing mild and efficient productivity. After that, bifunctional unsymmetrical di amination was developed by Yang et al. (Angewandte Chemie International Edition. 2022, vol. 61, e202212292). In terms of the 'bifunctional phosphoamine' derivatives, no effective derivative has been found in the literature to attempt the synthesis of the bifunctional phosphoaminating reagent.
The synthetic access to aminophosphonates in the conventional reactivity paradigms are mostly dependent on multistep reactions with harsh conditions that often use stoichiometric or superstoichiometric equivalents of acutely toxic and dangerous reagents such as alkali metals. These transformations, generally realized through ionic schemes of reactivity, due to their harsh conditions and reagents are unfit not only for sensitive substrates but also stand in contradiction to the goals of sustainable chemistry.
Therefore, the need exists, to address these problems and to provide a process for the synthesis of a bifunctional phosphoaminating reagent from cheap and available starting materials and use this for olefins functionalization. Further, the process should be able to avoid generation of unwanted side products and should be nontoxic, ecofriendly and economically favourable.

OBJECTS OF THE INVENTION:
It is therefore an object of this invention to propose a novel bifunctional phosphoaminating agent, a process for the preparation thereof and the application thereof in the synthesis of aminophosphonates/aminophosphonic acids.

It is a further object of this invention to propose a process for the preparation of a novel bifunctional phosphoaminating agent, which is environment friendly.

Another object of this invention is to propose a process for the preparation of a novel bifunctional phosphoaminating agent, which uses cheap and available starting materials.

Yet another object of this invention is to propose a process for the preparation of a novel bifunctional phosphoaminating agent, which avoids obnoxious side reactions and generation of stoichiometric waste.

A further object of this invention is to propose a process for the preparation of a novel bifunctional phosphoaminating agent, which is cost-effective and has superior performance compared to the common phosphoaminating agents.

These and other objects and advantages of the invention will be apparent from the ensuing description when read in conjunction with the accompanying drawings.


BRIEF DESCRIPTION OF THE ACCOMPANYING DRAWINGS:
Figure 1: ORTEP plot of compound E with 50% ellipsoid probability.


SUMMARY OF THE INVENTION:
According to this invention is provided a the synthesis and characterization of a new organic compound (E), and its application to the synthesis of aminophosphonates/aminophosphonic acids by reaction with various types of olefins via simultaneous generation of N- and P- centred radicals when subjected to visible-light mediated photocatalysis.


DETAILED DESCRIPTION OF THE INVENTION:
According to this invention is provided a novel bifunctional phosphoaminating agent, a process for the preparation thereof and the application thereof in the synthesis of aminophosphonates/aminophosphonic acids.
In the following description, numerous specific details are set forth in order to provide a thorough understanding of embodiments of the present disclosure. It will be apparent to one skilled in the art that embodiments of the present disclosure may be practiced without some of these specific details.
Accordingly, those of ordinary skill in the art will recognize that various changes and modifications of the embodiments described herein can be made without departing from the spirit and scope of the invention.
As used in the description herein and throughout the claims that follow, the meaning of "a," "an," and "the" includes plural reference unless the context clearly dictates otherwise. Also, as used in the description herein, the meaning of "in" includes "in" and "on" unless the context clearly dictates otherwise.
In the application, where an element or component is said to be selected from a list of recited elements or components, it should be understood that the element or component can be any one of the recited elements or components, or the element or component can be selected from a group consisting of two or more of the recited elements or components. Further, it should be understood that elements and/or features of a composition or a method described herein can be combined in a variety of ways without departing from the spirit and scope of the present teachings, whether explicit or implicit herein.
The use of the terms "include," "includes", "including," "have," "has," or "having" should be generally understood as open-ended and non-limiting unless specifically stated otherwise.
Throughout the application, where compositions are described as having, including, or comprising specific components, or where processes are described as having, including, or comprising specific process steps, it is contemplated that compositions of the present teachings can also consist essentially of, or consist of, the recited components, and that the processes of the present teachings can also consist essentially of, or consist of, the recited process steps.
In interpreting both the specification and the claims, all terms should be interpreted in the broadest possible manner consistent with the context. In particular, the terms "comprises" and "comprising" should be interpreted as referring to elements, components, or steps in a non- exclusive manner, indicating that the referenced elements, components, or steps may be present, or utilized, or combined with other elements, components, or steps that are not expressly referenced.
It will be understood by those skilled in the art with respect to any chemical group containing one or more substituents that such groups are not intended to introduce any substitution or substitution patterns that are sterically impractical and/or physically non-feasible.
Where a range of values is provided, it is to be understood that each intervening value, including the limiting values, to the tenth of the unit of the lower limit, unless the context clearly dictates otherwise, between the upper and lower limit of that range and any other stated or intervening value in that stated range, is encompassed within the described subject matter.
The technical expressions as used herein are standard expressions which will be apparent to a person skilled in the art as being a part of standard terminology.
It is to be understood that, for a clear understanding, the description of the present invention has been simplified to illustrate the relevant elements only. For the sake of clarity, other details that may be well known are omitted.
The expressions as used herein are standard expressions which will be apparent to a person skilled in the art as being a part of standard terminology.
The present invention relates to novel bifunctional phosphoaminating agent of formula (E).
The present invention further relates to a process for the preparation of the novel bifunctional phosphoaminating agent of formula (E).
Still further, the present invention relates to the application of the novel bifunctional phosphoaminating agent of formula (E) for the synthesis of aminophosphonates/aminophosphonic acids.
In accordance with this invention is provided a novel bifunctional phosphoaminating agent of formula (E),


The compound of formula (E) is synthesised from cheap and available starting materials and is used for olefin functionalization. The synthesized compound (E) is a colourless crystalline solid of high purity having monoclinic structure and fit for subsequent use. The present compound (E) is found to be stable under ambient conditions for more than one month and can be stored in a freezer for at least 6 months without any substantial decomposition. However, the said compound (E) is mildly sensitive to light, with slight decomposition being observed upon storage in a transparent glass bottle on an open benchtop for a long time. Hence, sealing the compound in a dark bottle under low temperature is recommended for prolonged storage. The route for the synthesis of the said invention (E) is through the sequential connection of three individual components. Initially, diphenyl oxime is coupled with 2-bromoisobutyric acid to generate an oxime ester. This is followed by the nucleophilic substitution by a phosphonated oxime to get the desired 'Bifunctional phosphoamination agent.
In accordance with this invention, the process for the preparation of the novel bifunctional phosphoaminating agent of formula (E) comprises the steps of coupling benzophenone oxime (A) with 2-bromoisobutyric acid (B) to generate an oxime ester (C), followed by the nucleophilic substitution by a phosphonated oxime (D) to obtain the bifunctional phosphoaminating agent of formula (E).
In order to have a better understanding of the invention, the process will be described in greater detail hereinbelow.
The benzophenone oxime derivative (A) is synthesized according to reported literature (Angewandte Chemie International Edition. 2020, vol. 59, page 3172-3177) from benzophenone and hydroxylamine hydrochloride under reflux in ethanol. The crude product is extracted by EtOAc and used directly for esterification with 2-bromoisobutyric acid (B). The crude product (C) is purified by column chromatography. The reaction scheme is presented in Scheme-1 below.

Scheme-1
The phosphonate oxime derivative diethyl-((hydroxyimino)(phenyl)methyl)phosphonate (D) is synthesized by the method of reported literature (Chemical Communications, 2019, vol. 55, page 11888 - 11891). Benzoyl chloride is charged into a RB equipped with a stirrer bar and triethyl phosphite is added dropwise at 0 ℃. After complete addition the reaction mixture is stirred at room temperature. The crude product is concentrated under vacuum and used in the next step without further purification. The crude product is dissolved in a solvent, and pyridine and hydroxylamine hydrochloride is added to the reaction medium followed by overnight stirring. Consumption of starting material is monitored and after completion, the reaction is quenched and the reaction mixture is worked up to obtain the crude product, which is purified to obtain the diethyl-((hydroxyimino)(phenyl)methyl)phosphonate (D) (Scheme- 2).

Scheme- 2
Diethyl-((hydroxyimino)(phenyl)methyl)phosphonate (D) thus obtained is dissolved in dimethyl formamide solvent along with potassium carbonate as base. Then diphenylmethanone O-(2-bromo-2- methylpropanoyl) oxime (C) was added to the former solution under stirring. The final product was isolated after purification by column chromatography to yield the product (E) as a white crystalline solid (72%). The reaction scheme is presented in Scheme-3 below.


Scheme-3

In accordance with this invention is further provided a process for the synthesis of aminophosphonates/aminophosphonic acids by reaction of the novel bifunctional phosphoaminating agent of formula (E), with various types of olefins via simultaneous generation of N- and P- centred radicals when subjected to visible-light mediated photocatalysis.

The invention will now be explained in greater details with the help of the following non- limiting examples. However, such examples are merely for the purpose of explaining the invention and are not to be construed as limiting the scope of the invention.
EXAMPLES:
Materials and Methods
Reactions were carried out using the following chemicals: Benzophenone (Spectrochem, India); Hydroxylamine hydrochloride (SRL, India); Sodium Acetate (SRL, India); Ethanol (Simsol, India); Benzoyl Chloride (Spectrochem, India); Triethyl Phosphite (Spectrochem, India); Pyridine (SRL, India), 2-Bromo-2-methylpropanoic acid (BLDpharm, India), Ethyl Acetate (Avantor, India).
NMR Characterization was obtained in Chloroform-D (Sigma, US) with locking onto the residual solvent peak. 1H spectra were recorded in Bruker-400 advance NMR spectrometer. Chemical shifts were reported in ppm downfield.
Example-1
Preparation of Phosphoaminating reagent: This reagent was synthesized according to the four consecutive reactions:
(a) Procedure for benzophenone oxime synthesis:
In a 250 mL RB connected with condenser was charged with corresponding benzophenone (50.0 mmol.), dissolved in EtOH/H2O (125 mL, v/v 4/1). Then, Hydroxylamine hydrochloride (80 mmol, 1.6 equiv.) and Sodium acetate (100 mmol, 2.0 equiv.) were added to the solution in one portion. The reaction mixture was refluxed for 12-14 h and the consumption of starting material was monitored by TLC. After completing the reaction, it was cooled to room temperature and concentrated in vacuo. The white residue was diluted with 60 mL of water and extracted with 180 mL (60 mL × 3) EtOAc. Then, the combined organic layer was washed with brine solution, dried over Na2SO4 and concentrated under reduced pressure. The white solid product was used for next step without further purification.

(b) Procedure for oxime ester synthesis from benzophenone oxime:
A 100 mL double-necked round-bottom flask was charged with benzophenone oxime A (10 mmol, equiv.), 2- bromoisobutyric acid (15 mmol, 1.5 equiv.) and DMAP (2 mmol, 0.2 equiv.). Dry DCM (20 mL) was added under argon atmosphere and allowed to stir for 5 min to get homogeneous. Then, DCC was added at 0 ℃. After addition, the reaction mixture was allowed to stir at room temperature for 10 to 12 h. Upon completion, the reaction mixture was filtered through a short pad of celite to remove the solids. The crude product was purified by column chromatography to get oxime ester (C).


(c) Procedure for Diethyl-((hydroxyimino)(phenyl)methyl)phosphonate synthesis:
Phosphoryl oxime was prepared according to the reported literature (Chemical Communications, 2019, vol. 55, page 11888 - 11891).
(i) A 100 mL RB equipped with a PTFE coated magnetic stirrer bar was charged with benzoyl chloride (22 mmol, 1.1 equiv.). Triethyl phosphite (20 mmol, 1 equiv.) was added dropwise at 0 ℃. After complete addition the reaction mixture was stirred for 2 h at room temperature. The crude product was concentrated under vacuum and used in the next step without further purification.
(ii) The above product was dissolved in EtOH (30 mL), and Pyridine (1.2 equiv.) and hydroxylamine hydrochloride (1.1 equiv.) were added to the reaction medium followed by overnight stirring. Consumption of starting material was monitored by TLC. After completion, the reaction was quenched by 1 N HCl solution and extracted with 60 mL (20 mL × 3) ethyl acetate. The combined organic layers were washed with water and brine solution, dried over Na2SO4 and concentrated under reduced pressure. The crude product was purified by flash column chromatography to obtain phosphonate oxime (D).


(d) Procedure for oxime ether synthesis from Phosphoryl-oxime:
Phosphoryl oxime (D) (15 mmol, 1.5 equiv.) was dissolved in DMF (10 mL) along with K2CO3 (15 mmol, 1.5 equiv.) followed by stirring for 10 min. Then, diphenylmethanone O-(2-bromo-2- methylpropanoyl) oxime (C) (10 mmol, 1 equiv.) was added to the reaction mixture at once and allowed to stir at room temperature for overnight. Upon completion, the reaction was quenched with 60 mL of water and extracted with 45 mL ethyl acetate (15 mL ×3). The combined organic layers were brine solution, dried over Na2SO4 and concentrated under reduced pressure. The crude product was purified by flash column chromatography using petroleum ether and ethyl acetate as eluent to the corresponding product (E).


Characterization of phosphoaminating agent:
Diethyl -(4,4-dimethyl-5-oxo-1,8,8-triphenyl-3,6-dioxa-2,7-diazaocta-1,7-dien-1- yl)phosphonate (E):

Yield: 67% (3.4 g).
Nature: white solid
Mp: 58 - 60°C
Rf value = 0.5 [EtOAc:Petroleum ether = 1:1 (v/v)].
1 H NMR (400 MHz, CDCl3) δ (ppm): δ 7.64 - 7.55 (m, 2H), 7.50 - 7.41 (m, 6H), 7.40 - 7.36 (m, 2H), 7.37 -7.34 (m, 2H), 7.33 - 7.28 (m, 3H), 4.19 - 4.04 (m, 4H), 1.43 (s, 6H), 1.26 (t, J = 7.1 Hz, 6H).
13C{1H} NMR (101 MHz, CDCl3) δ (ppm): 170.5, 165.9, 153.0, 150.9, 134.6, 132.6, 131.2, 129.8, 129.6, 129.5 129.2, 129.1, 129.1, 128.7, 128.6, 128.4, 128.1, 83.1, 63.86 (d, J = 6.4 Hz), 23.9, 16.4 (d, J = 6.5 Hz).
31P NMR (162 MHz, CDCl3) δ (ppm): 7.12.
HRMS (ESI) m/z calcd for C28H32N2O6P [M+H]+ : 523.1998; found: 523.1998.
XRD Analysis: X-ray Crystal Structures and Data of (E): The ORTEP plot of compound (E) with 50% ellipsoid probability is shown in Fig 1 of the accompanying drawings.
Crystal formation process: Recrystallization of (E) was performed in a 15 mL glass vial cover with aluminum foil, dissolving 50 mg of compound in 5 mL solvent [50% EtOAc/Petrolium ether (v/v)], and kept the vial in dark room for slow evaporation. After two days crystal was formed as colorless cubic shape.
Crystal data for (E): X-ray single crystal data were collected using MoKα (λ = 0.71073 Å) radiation on a Rigaku SuperNova diffractometer equipped with an Eos S2 detector. Structure solution/refinement were carried out using Shelx-2013. The structure was solved by direct method and refined in a routine manner. Non-hydrogen atoms were treated anisotropically. All hydrogen atoms were geometrically fixed. CCDC (CCDC No: 2358613) contains the supplementary crystallographic data of E (Figure 1). These data can be obtained free of charge via www.ccdc.cam.ac.uk/conts/retrieving.html (or from the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB21EZ, UK; fax: (+44) 1223-336-033; or deposit@ccdc.cam.ac.uk).


Bond precision: C-C = 0.0039 A Wavelength=0.71073
Cell: a=14.6909(7) b=10.2782(7) c=19.3927(10)
alpha=90 beta=104.525(5) gamma=90
Temperature: 293 K
Calculated Reported
Volume 2834.6(3) 2834.6(3)
Space group P 21/c P 21/c
Hall group -P 2ybc -P 2ybc
Moiety formula C28 H29 N2 O6 P ?
Sum formula C28 H29 N2 O6 P C28 H29 N2 O6 P
Mr 520.50 520.50
Dx,g cm-3 1.220 1.220
Z 4 4
Mu (mm-1) 0.139 0.139
F000 1096.0 1096.0
F000' 1096.93
h,k,lmax 18,13,24 18,13,24
Nref 6174 6074
Tmin,Tmax
Tmin'
Correction method= Not given
Data completeness= 0.984 Theta(max)= 26.998
R(reflections)= 0.0630( 4623) wR2(reflections)= 0.1901( 6074)
S = 1.071 Npar= 366


 
The phosphoaminating agent of formula (E) prepared according to the invention has been tested for its properties and efficiency in the synthesis of aminophosphonates/aminophosphonic acids. The results are presented hereinbelow.
Example-2
Procedure for the synthesis of 1,2-phosphoimine:

A flame dried culture tube equipped with a magnetic stirring bar was charged with Thioxanthone (TXT) (1 mg, 5 mol %), phosphoaminating agent (E) (208 mg, 0.4 mmol) and dry acetone (2 mL). Then Acrylonitrile (14 µL, 0.2 mmol) was added to the reaction tube and degassed by purging argon for a minute and sealed with a Teflon screw cap. Then the reaction mixture was irradiated at room temperature for 12 h with a 390 nm violet LED bulb at a distance of approximately 5 cm. A high-speed fan was used to maintain the temperature. After completion (checked by TLC), the solvent was evaporated and the crude residue was purified by flash column chromatography on silica gel 230-400 mesh (EtOAc:Petroleum ether = 40:60 - 80:20) to get the product diethyl-(2-cyano-2-((diphenylmethylene)amino)ethyl)phosphonate.
Diethyl-(2-cyano-2-((diphenylmethylene)amino)ethyl)phosphonate:

Yield: 74% (54 mg).
Nature: Colourless oil.
TLC= Rf: 0.2 [EtOAc: Petrolium ether = 1:1 (v/v)].
1H NMR (400 MHz, CDCl3) δ (ppm): 7.70 - 7.62 (m, 2H), 7.53 - 7.43 (m, 4H), 7.36 (t, J = 7.6 Hz, 2H), 7.26 (dd, J = 6.5, 2.9 Hz, 2H), 4.64 - 58 (dt, J = 9.6, 6.9 Hz, 1H), 4.09 - 4.00 (m, 4H), 2.52- 2.46 (m, 2H), 1.22 (dt, J = 14.1, 7.1 Hz, 6H).
13C{1H} NMR (101 MHz, CDCl3) δ (ppm): 174.2, 138.3, 135.0, 132.6, 131.5, 130.2, 129.7, 129.3, 129.2, 128.4, 128.3, 127.5, 118.68 (d, J = 15.6 Hz), 62.4 (d, J = 6.2 Hz), 62.2 (d, J = 6.4 Hz), 48.3 (d, J = 1.9 Hz), 31.7 (d, J = 142.3 Hz), 16.4 (d, J = 6.1 Hz), 16.3 (d, J = 6.1 Hz).
31P NMR (162 MHz, CDCl3) δ (ppm): 24.8.
HRMS (ESI) m/z calcd for C20H24N2O3P [M+H]+: 371.1525; found: 371.1519.

Example-3
Procedure for the synthesis of phosphonoalanine:


Compound diethyl-(2-cyano-2-((diphenylmethylene)amino)ethyl)phosphonate from Example-2 (74 mg, 0.2 mmol), 6 N HCl (2 mL) was taken sequentially to the 10 mL pear-shaped flask and the reaction mixture was heated to reflux for 20 hours. After completion (as monitored by TLC), the reaction mixture was diluted with 3 mL of deionized water and extracted with Et2O (2x3 mL). the water extract was concentrated in vacuo, diluted with absolute EtOH (4 mL) and treated with propylene oxide (1 mL). the resulting suspension was heated at 50°C for 2 hours. After cooling, the crude reaction mixture was concentrated in vacuo resulting in a white solid.
2-Amino-3-phosphonopropanoic acid:

Yield: 72% (24 mg).
Nature: white solid.
TLC= Rf: 0.2 [MeOH: DCM = 2:8 (v/v)].
1H NMR (400 MHz, D2O) δ (ppm): 3.88 (t, J = 11.2 Hz, 1H), 2.27 (t, J = 16.3 Hz, 1H), 1.98 (d, J = 10.2 Hz, 1H).
13C{1H} NMR (101 MHz, D2O) δ (ppm): 174.1, 67.2 (d, J = 133.8 Hz), 28.9 (d, J = 127.4 Hz).
31P NMR (162 MHz, D2O) δ (ppm): 18.8
Example-4
Procedure for the synthesis of 1,3-phosphoimine:

A flame dried culture tube equipped with a magnetic stirring bar was charged with Thioxanthone (TXT) (5 mg, 5 mol %), phosphoaminating agent (E) (208 mg, 0.4 mmol) and dry acetone (2 mL). Then 2,2-dimethyl-4-phenylhex-5-en-3-one (41 µL, 0.2 mmol) was added to the reaction tube and degassed by purging argon for a minute and sealed with a Teflon screw cap. Then the reaction mixture was irradiated at room temperature for 12 h with a 390 nm violet LED bulb at a distance of approximately 5 cm. A high-speed fan was used to maintain the temperature. After completion (checked by TLC), the solvent was evaporated and the crude residue was purified by flash column chromatography on silica gel 230-400 mesh (EtOAc:Petroleum ether = 40:60 - 80:20) to get the product diethyl (2-(((diphenylmethylene)amino)(phenyl)methyl)-4,4-dimethyl-3-oxopentyl)phosphonate.
Diethyl (2-(((diphenylmethylene)amino)(phenyl)methyl)-4,4-dimethyl-3-oxopentyl)phosphonate:

Yield: 49% (51 mg). (obtained as single syn-diastereoisomer)
Nature: Colourless oil.
TLC= Rf: 0.4 [EtOAc:Petroleum ether =4:6 (v/v)]. (Visualized by UV)
1H NMR (400 MHz, CDCl3) δ (ppm): 7.65 - 7.59 (m, 2H), 7.50 (dd, J = 11.2, 4.5 Hz, 2H), 7.46 - 7.42 (m, 1H), 7.40 - 7.33 (m, 5H), 7.29 (d, J = 7.6 Hz, 2H), 7.25 - 7.16 (m, 3H), 5.30 - 5.26 (m, 1H), 4.39 - 4.26 (m, 1H), 4.02 - 3.85 (m, 4H), 1.65 (d, J = 4.9 Hz, 1H), 1.62 - 1.59 (m, 1H), 1.14 (t, J = 7.1 Hz, 3H), 1.06 (s, 9H), 1.00 (t, J = 7.1 Hz, 3H).
13C{1H} NMR (101 MHz, CDCl3) δ (ppm): 214.8, 139.6, 136.7, 136.3, 130.1, 129.7, 128.7, 128.7, 128.4, 128.3, 128.0, 127.9, 127.4, 61.7 (d, J = 6.2 Hz), 61.6 (d, J = 6.3 Hz), 61.1 (d, J = 6.1 Hz), 56.8, 45.7, 28.5 (d, J = 140.8 Hz), 26.7, 16.4 (d, J = 6.4 Hz), 16.3(d, J = 6.8 Hz).
31P NMR (162 MHz, CDCl3) δ (ppm): 29.8.
HRMS (ESI) m/z calcd for C31H39NO4P [M+H]+ : 520.2617; found: 520.2615.

Example-5
Procedure for the synthesis of 1,4-phosphoimine:

A flame dried culture tube equipped with a magnetic stirring bar was charged with Thioxanthone (TXT) (2 mg, 5 mol %), phosphoaminating agent (E) (208 mg, 0.4 mmol) and dry Acetone (2 mL). Then Acrylonitrile (15 µL, 0.2 mmol) and ethyl vinyl ether (22 µL, 0.4 mmol) was added to the reaction tube and degassed by purging argon for a minute and sealed with a Teflon screw cap. Then the reaction mixture was irradiated at room temperature with a 390 nm violet LED bulb at a distance approximately 5 cm. A high-speed fan was used to maintain the temperature. After 12 h, completion the reaction (checked by TLC), the solvent was evaporated and the crude residue was purified by flash column chromatography on silica gel 230-400 mesh (EtOAc: Petroleum ether = 40:60 - 80:20) to get the corresponding phosphoamination product diethyl ((4)-4-cyano-4-((diphenylmethylene)amino)-2-ethoxybutyl)phosphonate.
Diethyl ((4)-4-cyano-4-((diphenylmethylene)amino)-2-ethoxybutyl)phosphonate:

Yield: 36% (32 mg). (combined yield as a 1:1 mixture of diastereomers)
Nature: Colourless oil.
TLC= Rf: 0.3 [EtOAc:Petroleum ether =1:1 (v/v)]. (Visualized by UV)
1H NMR (400 MHz, CDCl3) δ (ppm): (for the mixture) 7.71 - 7.60 (m, 2H), 7.53 - 7.50 (m, 3H), 7.47 - 7.42 (m, 1H), 7.35 (t, J = 7.7 Hz, 2H), 7.27 (d, J = 4.2 Hz, 1H), 7.23 (dd, J = 7.5, 1.9 Hz, 1H), 4.51 - 4.42 (m, 1H), 4.23 - 4.03 (m, 4H), 3.94 - 3.57 (m, 1H), 3.57 - 3.45 (m, 1H), 3.40 - 3.08 (m, 1H), 2.58 - 2.42 (m, 1H), 2.18 - 1.85 (m, 3H), 1.39 - 1.28 (m, 6H), 0.99 (dt, J = 22.2, 7.0 Hz, 3H).
13C{1H} NMR (101 MHz, CDCl3) δ (ppm): (for the mixture) 174.2, 173.1, 138.7, 138.5, 135.3, 135.2, 131.4, 131.3, 129.7, 129.4, 129.2, 129.1, 129.1, 129.0, 128.3, 127.7, 127.5, 119.9, 119.6, 71.5, 70.7, 65.0, 64.3, 62.0 (d, J = 6.3 Hz), 61.9 (d, J = 6.4 Hz), 61.8 (d, J = 6.4 Hz), 50.5, 49.1, 40.9, 40.9, 40.6, 40.7, 32.0(d, J = 138.0 Hz), 31.6 (d, J = 137.9 Hz), 16.6 (d, J = 5.9 Hz), 16.6 (d, J = 6.1 Hz), 15.2 (d, J = 1.2 Hz).
31P NMR (162 MHz, CDCl3) δ (ppm): 27.5, 27.4.
HRMS (ESI) m/z calcd for C24H31N2O4PK [M+K] + : 481.1659; found: 481.1651.

Example-6
Procedure for the synthesis of 1,5-phosphoimine:


A flame dried culture tube equipped with a magnetic stirring bar was charged with Thioxanthone (TXT) (2 mg, 5 mol%), phosphoamination reagent (E) (208 mg, 0.4 mmol) and dry Acetone (2 mL). Then 2-phenylhex-5-enenitrile (36 µL, 0.2 mmol) was added to the reaction tube and degassed by purging argon for a minute and sealed with a Teflon screw cap. Then the reaction mixture was irradiated at room temperature with a 390 nm violet LED bulb at a distance approximately 5 cm. A high-speed fan was used to maintain the temperature. After 12 h, completion the reaction (checked by TLC), the solvent was evaporated and the crude residue was purified by flash column chromatography on silica gel 230-400 mesh (EtOAc: Petroleum ether = 40:60 - 80:20) to get the corresponding phosphoamination product diethyl ((5)-2-cyano-5-((diphenylmethylene)amino)-5-phenylpentyl)phosphonate.
Diethyl ((5)-2-cyano-5-((diphenylmethylene)amino)-5-phenylpentyl)phosphonate:

Yield: 54% (53 mg). (combined yield as a 1:1 mixture of diastereomers)
Nature: colourless oil.
TLC= Rf: 0.3 [EtOAc: Petroleum ether = 1:1 (v/v)]. (Visualized by UV)
1H NMR (400 MHz, CDCl3) δ (ppm): (for the mixture)7.73 - 7.63 (m, 2H), 7.45 - 7.40 (m, 3H), 7.40 - 7.26 (m, 7H), 7.23 (dd, J = 6.2, 2.3 Hz, 1H), 7.03 (dd, J = 6.4, 2.9 Hz, 2H), 4.42 - 4.30 (m, 1H), 4.14 - 4.01 (m, 4H), 2.94 - 2.79 (m, 1H), 2.17 - 2.04 (m, 2H), 2.03 - 1.78 (m, 2H), 1.67 - 1.52 (m, 2H), 1.32 - 1.25 (m, 6H).
13C{1 H} NMR (101 MHz, CDCl3) δ (ppm): (for the mixture) 167.5, 144.2, 144.1, 139.7,1 39.7, 136.9, 138.8, 130.3, 128.7, 128.6, 128.2, 127.7, 127.1, 120.9, 120.9, 65.8, 65.6, 62.4 (d, J = 6.8 Hz), 62.3 (d, J = 6.4 Hz). 36.6, 36.5, 30.53(d, J = 10.2 Hz), 30.3 (d, J = 10.7 Hz), 28.9 (d, J = 140.4 Hz) 28.8 (d, J = 140.4 Hz) , 26.3 (t, J = 3.9 Hz), 16.5, 16.4.
31P NMR (162 MHz, CDCl3) δ (ppm): (for the mixture) 25.6, 25.5
HRMS (ESI) m/z calcd for C29H34N2O3P [M+H]+ : 489.2307; found: 489.2301.

Example-7
Procedure for the synthesis of 1,6-phosphoimine:


A flame dried culture tube equipped with a magnetic stirring bar was charged with Thioxanthone (TXT) (2 mg, 5 mol%), phosphoamination reagent (E) (208 mg, 0.4 mmol) and dry Acetone (2 mL). Then 2-(pent-4-en-1-yl)malononitrile (36 µL, 0.2 mmol) was added to the reaction tube and degassed by purging argon for a minute and sealed with a Teflon screw cap. Then the reaction mixture was irradiated at room temperature with a 390 nm violet LED bulb at a distance approximately 5 cm. A high-speed fan was used to maintain the temperature. After 12 h, completion the reaction (checked by TLC), the solvent was evaporated and the crude residue was purified by flash column chromatography on silica gel 230-400 mesh (EtOAc:Petroleum ether = 40:60 - 80:20) to get the corresponding phosphoamination product diethyl (6,6-dicyano-6-((diphenylmethylene)amino)hexyl)phosphonate.
Diethyl (6,6-dicyano-6-((diphenylmethylene)amino)hexyl)phosphonate:

Yield: 66% (60 mg).
Nature: Colourless oil.
TLC= Rf: 0.2 [EtOAc:Petroleum ether =1:1 (v/v)]. (Visualized by UV)
1H NMR (400 MHz, CDCl3) δ (ppm): 7.67 - 7.61 (m, 2H), 7.61 - 7.53 (m, 3H), 7.53 - 7.48 (m, 1H), 7.42 - 7.36 (m, 4H), 4.15 - 4.05 (m, 4H), 2.48 - 2.38 (m, 2H), 1.80 - 1.73 (m, 4H), 1.70 - 1.65 (m, 2H), 1.61 - 1.53 (m, 2H), 1.33 (t, J = 7.1 Hz, 6H).
13C{1H} NMR (101 MHz, CDCl3) δ (ppm): 177.2, 138.5, 133.7, 132.4, 130.8, 129.6, 128.9, 128.7, 128.5, 114.3, 61.7 (d, J = 6.5 Hz), 53.2, 43.6, 29.9, 29.7, 25.7 (d, J = 141.2 Hz), 24.0, 22.4, 22.5, 16.6 (d, J = 6.0 Hz).
31P NMR (162 MHz, CDCl3) δ (ppm): 31.8.
HRMS (ESI) m/z calcd for C25H31N3O3P [M+H] +: 452.2103; found: 452.2101.

The present invention provides a phosphoaminating agent and a sustainable method for introducing two functional groups that are traditionally difficult to incorporate, namely amine and phosphonate. The phosphoaminating according to the invention can be readily constructed from cheap starting materials that can be easily sourced. The invention provides a way for step-economic incorporation of the said functional groups in a operationally simple manner. Light of visible wavelength is used as a source of energy which makes this process a green alternative to traditional thermal methods.
The present invention adopts a bench-stable and easily accessible bifunctional reagent for the simultaneous incorporation of amine and phosphonate groups in a synthetically mild procedure. The said reagent is activated by visible-light induced photocatalysis leading to the generation of an N-centred amine radical and a P-centred phosphonate radical. Their subsequent attachment to various feedstock olefins, leading to various classes of aminophosphonates/aminophosphonic acids namely, 1,2-, 1,3-, 1,4-, 1,5-, 1,6-aminophosphonates. The invention is also a step towards building a more sustainable chemical process as the activation of the said reagent is mediated by irradiation of light in the visible range of the wavelength while also incorporating cheaply available feedstock alkenes. , Claims:CLAIMS:
1. A bifunctional phosphoaminating agent diethyl -(4,4-dimethyl-5-oxo-1,8,8-triphenyl-3,6-dioxa-2,7-diazaocta-1,7-dien-1-nyl)phosphonate of formula (E).

2. A process for the preparation of the phosphoaminating agent of formula (E), which comprises the steps of coupling diphenyl oxime (A) with 2-bromoisobutyric acid (B) to generate an oxime ester (C), followed by the substitution of the oxime ester (C) by a phosphonate oxime (D) to obtain the bifunctional phosphoaminating agent of formula (E).
3. The process as claimed in claim 2, wherein the step of coupling benzophenone oxime (A) with 2-bromoisobutyric acid (B) comprises adding hydroxylamine hydrochloride to benzophenone in a solvent, in the presence of a base, and refluxing the mixture for 12-14 hours to obtain diphenyl oxime (A), followed by subjecting the diphenyl oxime to esterification with 2-bromoisobutyric acid (B) to obtain an oxime ester, diphenylmethanone O-(2-bromo-2- methylpropanoyl) oxime (C).
4. The process as claimed in claim 2, wherein the phosphonate oxime derivative (D) is prepared by adding triethyl phosphite to acid chloride, with stirring at 0 ℃, concentrating the crude product and dissolving the same in in a solvent, adding pyridine and hydroxylamine hydrochloride to the reaction medium followed by overnight stirring, to obtain the phosphonate oxime (D).
5. The process as claimed in claim 2, wherein the substitution of the oxime ester (C) by a phosphonate oxime (D) comprises dissolving phosphonate oxime (D) in a solvent along with potassium carbonate as base, followed by adding diphenylmethanone O-(2-bromo-2- methylpropanoyl) oxime (C) to the solution under stirring, to obtain the product (E).
6. A process for the preparation of 1,2-phosphoimine, diethyl (2-cyano-2-((diphenylmethylene)amino)ethyl)phosphonate by subjecting the bifunctional reagent (E) as claimed in claim 1, to a reaction with acrylonitrile using a photocatalytic procedure as depicted in (Example-2).
7. A process for the preparation of 1,3-phosphoimine, diethyl (2-(((diphenylmethylene)amino)(phenyl)methyl)-4,4-dimethyl-3-oxopentyl)phosphonate by subjecting the bifunctional reagent (E) as claimed in claim 1, to a reaction with 2,2-dimethyl-4-phenylhex-5-en-3-one using a photocatalytic procedure as depicted in (Example-4).
8. A process for the preparation of 1,4-phosphoimine, diethyl ((4)-4-cyano-4-((diphenylmethylene)amino)-2-ethoxybutyl)phosphonate by subjecting the bifunctional reagent (E) as claimed in claim 1, to a reaction with acrylonitrile and ethyl vinyl ether using a photocatalytic procedure as depicted in (Example-5).
9. A process for the preparation of 1,5-phosphoimine, diethyl ((5)-2-cyano-5-((diphenylmethylene)amino)-5-phenylpentyl)phosphonate by subjecting the bifunctional reagent (E) as claimed in claim 1, to a reaction with 2-phenylhex-5-enenitrile using a photocatalytic procedure as depicted in (Example-6).
10. A process for the preparation of 1,6-phosphoimine, diethyl (6,6-dicyano-6-((diphenylmethylene)amino)hexyl)phosphonate by subjecting the bifunctional reagent (E) as claimed in claim 1, to a reaction with 2-(pent-4-en-1-yl)malononitrile using a photocatalytic procedure as depicted in (Example-7).

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