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Environmentally Green Synthesis of α-aminophosphonates

Der Pharma Chemica
Journal for Medicinal Chemistry, Pharmaceutical Chemistry, Pharmaceutical Sciences and Computational Chemistry

ISSN: 0975-413X
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Research Article - Der Pharma Chemica ( 2021) Volume 13, Issue 11

Environmentally Green Synthesis of α-aminophosphonates

Rahul Patil*
 
Department of Chemistry, Yashwantrao Chavan College of Science, Karad, Maharashtra, India
 
*Corresponding Author:
Rahul Patil, Department of Chemistry, Yashwantrao Chavan College of Science, Karad, Maharashtra, India, Email: rspatilorg@gmail.com

Abstract

One pot multicomponent condensation of aldehyde, amine and diethylphosphite for the synthesis of α-aminophosphonates catalysed by environmentally green EPZG catalyst was found to be efficient and direct protocol under solvent free condition at room temperature. The green process offers advantages such as simple work up procedure, shorter reaction time, high yield and reusability of the catalyst.

Keywords

α-aminophosphonates; environmentally green; EPZG; diethylphosphit

Introduction

Organic chemistry deals with study of C-C bonds and a few compounds carry C-P bonds. Organo phosphorous compounds are made from the Phosphorous naturally or synthetically [1]. Attraction of the chemists increases towards these compounds due to their antibacterial, antimicrobial, antiviral, enzyme inhibitory properties and plant growth regulators, anti-cancer, [2-6]. The innovation of the amino phosphonic acid and other biologically active compound has wide purpose in agricultural and medicinal field [7-9]. Some organophosphorous compounds are key for pesticides [10], bactericides [11-13], α-pyrones analog of phosphorus act as HIV protease inhibitors [14]. Among the organo phosphorous compound α-aminophosphonic acid is significant motifs due to structural similarities with α-aminoacids [15-16]. The majority of the ester and acid derivatives of α-aminophosphonic acid has demonstrate advanced biological activity such as herbicidal and anticancer [17-22].

Kabachnik M. [23-25] and Fields E. [26] reported primary synthesis of α-amnophosphonic acid by the route of condensation of aldehyde or ketone with amine and dialkyl phosphate, latter on many reported technique used for the synthesis of α-aminophosphonates such as Indium triflate and Ytterbium triflate [27], gallium triiodide [28], VCl3 [29], silica sulfuric acid [30], copper salt [31], tetramethylguanidine [32], samarium di-iodide [33], lithium perchlorate [34], organocatalyst (R)-3,3’[4-fluorophenyl]2-1,1’-bisnaphthol phosphate [44], ionic liquid media [bmim][PF6] [35], Amberlite-IR 120 [36], L-Lactic Acid [37], ZrOCl2.8H2O and ZrO(ClO4)2.6H2O, diterpinic dehydroabietylamine [38] Nickel (II) chloride Hexahydrate, N,N′-dioxide-Sc (III) complex [39], Mg(ClO4)2 or molecular iodine [40], InCl3 [41], Montmorillonite KSF, Amberlyst-15 and Amberlite-IR 120 [42], microwave irradiation [43]. But, one pot multicomponent synthesis of α-aminophosphonates reported methods have drawbacks like long reaction time, use of organic solvent, reactivity with catalyst, completed separation procedure. To overcome this drawback, here in we have reported the synthesis of α-aminophosphonates by the application of environmentally benign inorganic, heterogeneous EPZG as a clay catalyst having Lewis acid and Bronsted acidic property. Envirocat EPZGR synthesized and supplied by Contract Chemicals, UK [44-54].

Materials and Methods

Various substitutedaldehyde (Sigma-aldrich), aniline (Himedia), diethylphosphite (Himedia) were used as received without purification. Envirocat EPZGR synthesized and supplied by Contract Chemicals, UK. Melting point measured by melting point apparatus made by Equiptronics model No. – EQ- 730A IR spectra were recorded on FT-IR -7600 Lambda Scientific Spectrometer.NMR Spectra were recorded on a Bruker AC400 MHz spectrometer in CDCl3 using tetramethylsilane as an internal standard material.

General Experimental Procedure

In a 25mlof round bottom flask mixture of aldehyde (1mmol), aniline (1mmol) and diethylphosphite (1mmol) was stirred with EPZ-GR [48-54] catalyst 20mg (Scheme 1) at room temperature for desired time mentioned in Table 4 (Entry a-v) completion of reaction was monitored by TLC. Upon completion of reaction separation and purification of product was carried out from ethanol. After completion of reaction catalyst was removed washed with water with ethyl acetate and reused for further reaction. All the products were purified by same technique and physical constant were found to be correct. Further structures of the product were confirmed by 1H NMR, 13C NMR, DEPT 135 NMR, HRMS and IR.

Result and Discussion

The use of solid heterogeneous catalyst EPZG catalyst was found to be environmentally green catalyst has attracted much attention in organic synthesis due to their advantages such as acidic property, reusability, inexpensive, low cost, and easy of handling, high yield of the product at room temperature. Model reaction using 20mg EPZGR under neat condition at room temperature agreeably results were obtained with respect to yield and reaction time monitored by TLC (Table1).

Table 1: Screen of catalyst for the synthesis of α-aminophosphonates

Sr. No. Catalyst Amount mg Time in (min) Yield%
1 EPZGR 10 34 84
2 EPZGR 20 22 90
3 EPZGR 30 22 90
4 EPZGR 40 22 90
5 EPZGR 40 22 90

Reaction conditions: Anisaldehyde (1mmol); aniline (1mmol); diethylphosphite (1mmol), solvent free, EPZGR catalyst 20mg, room temperature.

Reusability

The catalyst was found to be effective for the present transformation up to five cycles with appreciable loss in yield (Table 2).

Table 2: Reusability of catalyst for the synthesis of α-aminophosphonates

Run 1 2 3 4 5
Yield 90 89 88 87 86

Reaction conditions: Anisaldehyde (1mmol); aniline (1mmol); diethylphosphite (1mmol), solvent free, EPZGR catalyst 20mg, room temperature.

Screen of solvent: The present transformation was carried out with different solvents the results obtained predicted that the reaction performed under solvent free condition was effective having high yield at room temperature (Table 3).

Table 3: Screen of solvent for the synthesis of α-aminophosphonates

Entry Solvent Time Min. Yield%
1 Water 60 64
2 Alcohol 45 59
3 Solvent free 22 90
4 Chloroform 55 56
5 Dichloromethane 63 71
6 Dimethylsulphoxide 90 78

Reaction conditions: Anisaldehyde (1mmol); aniline (1mmol); diethylphosphite (1mmol), solvent free, EPZGR catalyst 20mg, room temperature

Spectral data of Synthesized α-aminophosphonates

Table 4, Entry a: Diethyl[(4-methoxyphenyl) (phenylamino)] methylphosphonate, Color: White; M. P.: 102-102ºC; IR (KBr) cm-1: 3300, 3150, 3000, 1600, 1500, 1330, 1210, 750,700; 1H NMR(400MHz, CDCl3):δ(ppm):1.14-1.17(t, 3H, -CH3, J= 8 Hz),1.29 - 1.32(t, 3H, -CH3, J = 8 Hz), 3.68-3.74(m, 1H, -OCH2, J= 4 Hz),3.79(s, 3H, -OCH3), 3.93-4.0(m, 1H, -OCH2, J = 4 Hz),4.10-4.17(m, 2H, -OCH2,J= 4 Hz),4.70-4.76(d, 1H, CH, 2JHP = 24 Hz), 6.60-7.42(m, Ar-H); 13C NMR(100 MHz, CDCl3): δ (ppm): 16.28(d, 3Jcp = 6.0 Hz, –CH3-P),16.46(d, 3Jcp = 5.0 Hz, –CH3-P), 55.23(s,-OCH3), 55.35(d, 1Jcp = 151 Hz,-CH-P),63.18(d, 2Jcp = 5.0 Hz, -CH2-P),63.25(d, 2Jcp = 5.0 Hz, -CH2-P ),113.89, 114.04,114.07, 118.34, 127.66, 127.69, 128.93,128.99, 129.15for aromatic carbon, 146.36(d, 2Jcp = 14.00 Hz, Ar-P), 159.29 (d, 3Jcp = 3.00 Hz, Ar-P); DEPT 135 NMR:δ (ppm): 63.19 (d, 2Jcp = 5.0 Hz, -CH2-P), 63.25(d, 2Jcp = 5.0 Hz, -CH2-P).

Table 4, Entry b: Diethyl[(phenyl)(phenylamino)] methylphosphonate, Color: White; M. P.: 90-92ºC; IR (KBr) cm-1: 3300, 3000, 1600, 1500,1200, 1010, 750, 700;1H NMR(400MHz, CDCl3): δ (ppm): 1.17-1.20(t, 3H, -CH3, J = 8 Hz), 3.66-3.72(m, 1H, -OCH2, J = 4 Hz),3.91-3.99(m, 1H, -OCH2, J = 4 Hz), 4.08-4.19(m, 2H, -OCH2, J = 4 Hz),4.75-4.81(d, 1H, -CH, 2JHP = 24 Hz), 6.63-7.48(m, Ar-H);13C NMR(100 MHz, CDCl3): δ( ppm):16.21(d, 3Jcp = 6.0 Hz, –CH3-P),16.45(d, 3Jcp = 6.0 Hz, –CH3-P),56.05(d, 1Jcp = 149 Hz,-CH-P), 63.25(d, 2Jcp = 4.0 Hz, –CH2-P), 63.32(d, 2Jcp = 4.0 Hz, –CH2-P),113.85, 118.39, 127.83, 127.88,127.92, 127.95, 128.60, 128.62, 129.18 for aromatic carbon, 135.89(d, 2Jcp = 3.00 Hz, , Ar-P ),146.31(d, 3Jcp = 15.00 Hz, Ar-P);DEPT 135 NMR:δ(ppm): 63.32(d, 2Jcp = 4.0 Hz, –CH2-P),63.25(d, 2Jcp = 4.0 Hz, –CH2-P);HRMS: 319.19;Calculated mass: 319.33.

Table 4, Entry d :Diethyl[(4-methylphenyl) (phenylamino)] methylphosphonate,Color: White; M. P.: 65ºC; IR (KBr) cm-1: 3300, 3100, 3000, 2900, 1600, 1500, 1220, 1010, 700, 650;1H NMR(400MHz, CDCl3): δ(ppm): 1.12-1.15(t, 3H, -CH3, J = 8 Hz),1.27-1.31(t, 3H, -CH3, J = 8 Hz), 2.31 (s, 3H, -CH3-Ar),3.66-3.72(m, 1H, -OCH2, J= 8 Hz),3.92-3.98(m, 1H, -OCH2, J = 8 Hz),4.08-4.15(m, 2H, -OCH2, J= 8 Hz),4.71-4.77(m, 1H, 2JHP= 24 Hz), 6.58-7.59(m, Ar-H) ;13C NMR (100 MHz, CDCl3 ):δ (ppm):16.23(d, 3Jcp = 6.0 Hz, -CH3-P), 16.4(d, 3Jcp = 6.0 Hz, -CH3-P),21.15(s,-CH3),55.07 (d, 1Jcp = 150 Hz,-CH-P), 63.20(d, 2Jcp = 3.0 Hz, -OCH2- P), 63.27(d, 2Jcp = 4.0 Hz, -OCH2-P),113.84, 118.31, 127.72,129.14, 129.31, 129.33,132.64, 132.67,137.59 for aromatic carbon,137.61(d, 2Jcp = 4.00 Hz , Ar-P),146.03(d, 3Jcp = 14.00 Hz, Ar-P);DEPT 135 NMR:δ(ppm): 63.21(d, 2Jcp = 4.0 Hz, -OCH2-P), 63.27(d, 2Jcp = 3.0 Hz, -OCH2-P).

Table 4, Entry f :Diethyl[(4-chlorophenyl)(phenylamino)] methylphosphonate, Color: White; M. P.: 58-59ºC; IR (KBr) cm-1:3300, 3100, 3000, 2950, 1590, 1250, 1000, 750, 600.1H NMR(400MHz, CDCl3):δ(ppm): 1.16-1.20(t, 3H, -CH3, J = 8 Hz),1.29-1.33(t, 3H, -CH3, J = 8 Hz), 3.76-3.83(m, 1H, -OCH2, J = 14 Hz),3.98-4.01(m, 1H, -OCH2, J= 12 Hz), 4.10-4.17(m, 2H, -OCH2, J = 12 Hz), 4.72-4.78(d, 1H, -CH, 2JHP= 24 Hz), 6.57-7.45(m, Ar-H);13C NMR (100 MHz, CDCl3):δ(ppm):16.29(d, 3Jcp = 6.0 Hz, -CH3-P),16.44(d, 3Jcp = 6.0 Hz, -CH3-P ),55.54(d, 1Jcp = 150 Hz,-CH-P), 63.36(d, 2Jcp = 6.0 Hz, -OCH2-P), 63.45(d, 2Jcp = 6.0 Hz, -OCH2-P),113.85, 118.68,128.80, 128.82, 129.12, 129.17, 129.24,133.71,133.75,for aromatic carbon, 134.58(d, 2Jcp = 3.00 Hz , Ar-P), 146.01(d, 3Jcp = 14.00 Hz, Ar-P); DEPT 135 NMR:δ(ppm): 63.36(d, 2Jcp = 6.0 Hz, -OCH2-P), 63.45(d, 2Jcp = 8.0 Hz, -OCH2-P).

Table 4, Entry h :Diethyl[(2-nitrophenylphenyl)(phenylamino)] methylphosphonate ,Color:brown; M. P.: 148-150ºC; IR (KBr) cm-1: 3300, 3000, 2900, 1600, 1500, 1220, 1000, 750, 700; 1H NMR(400MHz, CDCl3): δ(ppm): 1.09-1.13(t, 3H, -CH3, J = 4 Hz, ), 1.31-1.33(t, 3H, -CH3, J = 4 Hz), 3.79-3.85(m, 1H, -OCH2, J = 8 Hz),3.93-3.98(m, 1H, -OCH2, J = 4 Hz),4.16-4.21(m, 2H, -OCH2, J = 10 Hz),6.17-6.22(d, 1H, -CH, 2JHP= 24 Hz),6.68-8.02(m, Ar-H); 13C NMR (100 MHz, CDCl3): δ (ppm): 15.96(d, 3Jcp = 6.0 Hz, -CH3-P),16.33(d, 3Jcp = 6.0 Hz, -CH3-P), 49.93(d, 1Jcp = 150 Hz,-CH-P ), 63.39(d, 2Jcp= 7.0 Hz, -OCH2-P),63.87(d, 2Jcp = 7.0 Hz, -OCH2-P), 113.57, 118.85,125.27, 125.29, 128.53,128.56, 128.75, 128.79,129.45, 131.95, 131.97, 133.52, 133.55 for aromatic carbon, 145.33(d, 2Jcp = 13.00 Hz , Ar-P), 149.44(d, 3Jcp = 6.00 Hz, Ar-P);DEPT 135 NMR: δ(ppm): 63.39(d, 2Jcp = 7.0 Hz, -OCH2-P), 63.87(d, 2Jcp = 7.0 Hz, -OCH2-P);

Table 4, Entry j :Diethyl[(4-nitrophenyl) (phenylamino)] methylphosphonate, Color: Yellow; M. P.: 185-160ºC; IR (KBr) cm-1: 3300, 3050, 3000, 2900, 1600, 1500, 1350, 1210, 1020, 750, 700;1H NMR(400MHz, CDCl3): δ(ppm): 1.19-1.23(t, 3H, -CH3,J = 8Hz), 2.45-2.49(t, 3H, -CH3, J =8Hz),3.87-4.05(m, 1H, -OCH2, J = 4Hz),4.07-4.21(m,3H, from two -OCH2,J = 4Hz), 4.85-4.91(d, 1H, -CH, 2JHP = 24Hz),6.54-8.23(m, Ar-H); 13C NMR (100 MHz, CDCl3): δ(ppm):16.27(d, 3Jcp = 6.0 Hz, -CH3-P),16.44(d, 3Jcp = 6.0 Hz, -CH3-P), 56.01(d, 1Jcp = 147 Hz,-CH-P), 63.49(d, 2Jcp = 7.0 Hz, -OCH2-P), 63.76(d, 2Jcp = 7.0 Hz, -OCH2-P),113.80, 119.11, 123.77, 123.79, 128.63, 128.68, 129.37, 144.06, 144.10, for aromatic carbon,145.64(d, 2Jcp = 14.00 Hz, Ar-P),147.61(d, 3Jcp = 4.00 Hz, Ar-P);DEPT 135 NMR:δ(ppm): 63.49(d, 2Jcp = 7.0 Hz, -OCH2-P),63.76(d, 2Jcp = 7.0 Hz, -OCH2-P) ; HRMS: 364.19; Calculated mass:364.61.

Table 4, Entry l : Diethyl[(4-hydroxyphenyl)(phenylamino)] methylphosphonate

Color: White; M. P.: 102-104ºC; IR (KBr) cm-1:3350, 3250, 3000, 1600, 1510, 1230, 1010, 730, 700; 1H NMR( 400MHz, CDCl3 ): δ(ppm): 1.15-1.19 (t, 3H, -CH3, J = 8 Hz), 1.27-1.30(t, 3H, -CH3, J = 8 Hz), 3.74-3.81(m, 1H, -OCH2, J = 12 Hz), 3.95-4.01 (m, 1H, -OCH2,J= 4 Hz), 4.06-4.18(m, 2H, -OCH2, J = 4 Hz),4.69-4.75(d, 1H, -CH, 2JHP = 24 Hz), 6.60-7.27(m, Ar-H), 7.64(bs, Ar-OH); 13C NMR (100 MHz, CDCl3 ): δ(ppm): 16.25(d, 3Jcp = 5.0 Hz, -CH3-P ), 16.42(d, 3Jcp =5.0 Hz, -CH3-P),55.21(d, 1Jcp = 153 Hz,-CH-P), 63.47(d, 2Jcp = 7.0 Hz, -OCH2-P),63.65(d, 2Jcp = 7.0 Hz, -OCH2-P),113.94, 115.97, 116.00, 118.46, 125.89, 125.92, 128.87, 128.92, 129.17for aromatic carbon, 146.21(d, 2Jcp = 14.00 Hz , Ar-P), 156.52(d, 3Jcp = 3.00 Hz, Ar-P );DEPT 135 NMR:δ(ppm):63.47(d, 2Jcp = 7.0 Hz, -OCH2-P ),63.65(d, 2Jcp = 7.0 Hz, -OCH2-P).

Table 4, Entry n :Diethyl[(4-isopropylphenyl)(4-methoxyphenylamino)] methylphosphonate, Color: White; M. P.: 82-84ºC; IR (KBr) cm-1:3301, 2973, 1500, 1234, 1035, 932, 828; 1H NMR(400MHz, CDCl3):δ(ppm):1.10-1.12(t, 3H, -CH3, J = 8 Hz), 1.20-1.22(t, 3H, -CH3, J = 8 Hz), 3.65-3.71 (m, 3H, -OCH3), 3.90-3.96(m, 1H, -OCH2, J = 4 Hz), 4.08-4.14(m, 3H, -OCH2, J = 4 Hz), 4.64-4.70(d, 1H, -CH, 2JHP = 28 Hz), 6.55-7.37(m, Ar-H); 13C NMR (100 MHz, CDCl3):δ(ppm): 16.14(d, 3Jcp = 5.0 Hz, -CH3-P),16.43(d, 3Jcp = 5.0 Hz, -CH3-P),55.63 (s, -OCH3), 56.59(d, 1Jcp = 151 Hz,- CH-P),63.14(d, 2Jcp = 8.0 Hz, -OCH2-P),63.21(d, 2Jcp = 6.0 Hz, -OCH2-P),114.69, 115.15,126.64, 126.66, 127.69,127.75,133.11, 133.13for aromatic carbon, 140.45(d, 2Jcp = 16.00 Hz , Ar-P), 148.52(d, 3Jcp = 4.00 Hz, Ar-P), 152.85(s, Ar-O); DEPT 135 NMR:δ(ppm): 63.15(d, 2Jcp = 6.0 Hz, -OCH2-P).

Table 4, Entry p: Diethyl[(4-methylphenyl)(4-methoxyphenylamino)] methylphosphonate, Color: White; M. P.: 78-80ºC; IR (KBr) cm-1:3291, 2976, 1506, 1236, 1446, 1008, 807, 755;1H NMR(400MHz, CDCl3): δ(ppm):1.05-1.09(t, 3H, -CH3, J = 8 Hz), 1.20-1.24(t, 3H, -CH3, J = 4 Hz), 2.24(s, 3H, -CH3), 3.61-3.67(m, 3H, -OCH3), 3.85-3.91(m, 1H, -OCH2, J = 4 Hz), 4.00-4.08(m, 3H, 2-OCH2, J = 4 Hz), 4.57-4.63(d, 1H, -CH, 2JHP = 24 Hz), 6.74-7.27(m, Ar-H); 13C NMR (100 MHz, CDCl3): δ(ppm): 16.19(d, 3Jcp = 6.0 Hz, -CH3-P ),16.40(d, 3Jcp = 6.0 Hz, -CH3-P), 21.10(s,CH3-Aromatic), 55.56(s, -OCH3),56.52(d, 1Jcp = 151 Hz,-CH-P ),63.10(d, 2Jcp = 5.0 Hz, -OCH2-P),63.16(d, 2Jcp = 7.0 Hz, -OCH2- P),114.63, 115.16, 127.67,127.73, 129.22, 129.25,132.78, 132.81 for aromatic carbon, 137.47(d, 2Jcp = 3.00 Hz , Ar-P), 140.36(d, 3Jcp = 16.00 Hz, Ar-P), 152.49(s, Ar-O); DEPT 135 NMR:δ(ppm):63.11(d, 2Jcp = 6.0 Hz, -OCH2-P), 63.17(d, 2Jcp = 5.0 Hz, -OCH2-P).

Table 4, Entry r :Diethyl[(4-methoxyphenyl)(4-nitrophenylamino)] methylphosphonate, Color: White; M. P.: 128-130ºC; IR (KBr) cm-1: 3291, 2985, 1594, 1498, 1287, 1218, 999, 834, 763 cm-1; 1H NMR(400MHz, CDCl3): δ(ppm):1.11-1.15(t, 3H, -CH3, J = 8 Hz), 1.29-1.32(t, 3H, -CH3, J = 8 Hz), 3.61-3.67(m, 1H, -OCH2, J = 8 Hz), 3.78(s, 3H, -OCH3), 3.90-3.96(m, 1H, -OCH2, J = 8 Hz),4.104.17(m, 2H, -OCH2, J = 4 Hz), 4.73-4.79(d, 1H, -CH, 2JHP = 24 Hz), 6.57-8.02(m, Ar-H): 13C NMR (100 MHz, CDCl3): δ (ppm):16.24(d, 3Jcp = 6.0 Hz, -CH3-P),16.43(d, 3Jcp = 6.0 Hz, - CH3-P ),54.81(d, 1Jcp = 153 Hz,-CH-P),55.27(s, -OCH3),63.46(d, 2Jcp = 7.0 Hz, -OCH2-P),63.90(d, 2Jcp = 7.0 Hz, -OCH2-P),112.42, 114.33, 114.35,126.05, 126.14, 126.18, 128.89, 128.89, 138.96for aromatic carbon, 151.89(d, 2Jcp = 14.00 Hz , Ar-P),159.69(d, 3Jcp = 3.00 Hz, Ar-P ); DEPT 135 NMR:δ(ppm):63.33(d, 2Jcp = 8.0 Hz, -OCH2-P), 63.90(d, 2Jcp = 7.0 Hz, -OCH2-P).

Table 4, Entry t :Diethyl[(3-nitrophenyl)(4-nitrophenylamino)] methylphosphonate, Color: Yellow green; M. P.: 172-174ºC; IR (KBr) cm-1: 3264, 3072, 2985, 1621, 1542, 1305, 1209, 1017, 843, 755, 659; 1H NMR(400MHz, CDCl3): δ (ppm): 1.18-1.22(t, 3H, -CH3, J = 8 Hz), 1.31- 1.34(t, 3H, -CH3, J = 8 Hz), 3.86-3.93(m, 1H, -OCH2,J= 4 Hz), 4.03-4.09(m, 1H, -OCH2, J = 4 Hz), 4.16-4.25(m, 2H, -OCH2, J = 8 Hz), 4.94- 5.00(d, 1H, -CH, 2JHP = 24 Hz), 6.59-8.36(m, Ar-H); 13C NMR (100 MHz, CDCl3 ): δ (ppm): 16.24(d, 3Jcp = 6.0 Hz, -CH3-P), 16.30(d, 3Jcp = 6.0 Hz, -CH3-P),54.98(d, 1Jcp = 150 Hz,-CH-P),63.95(d, 2Jcp = 8.0 Hz, -OCH2-P),64.03(d, 2Jcp = 8.0 Hz, -OCH2-P),112.43, 122.55, 122.60, 123.42, 123.44, 126.12, 129.84,129.87, 133.67, 133.72,137.48, 137.50, 139.45for aromatic carbon, 148.54(d, 2Jcp = 2.00 Hz , Ar-P), 151.36(d, 3Jcp = 13.00 Hz, Ar-P); DEPT 135 NMR:δ(ppm):63.95(d, 2Jcp = 8.0 Hz, -OCH2-P).

Table 4, Entry v:Diethyl[(phenyl)(4-nitrophenylamino)] methylphosphonate, Color: Yellow; M. P.: 145-146ºC ; IR (KBr) cm-1: 3255, 3089, 2958, 1594, 1489, 1340, 1227, 1017, 965, 834, 675; 1H NMR(400MHz, CDCl3): δ (ppm):1.09-1.12(t, 3H, -CH3, J = 8 Hz), 1.14-1.16(t, 3H, -CH3, J = 8 Hz), 3.60-3.64(m, 1H, -OCH2, J = 8 Hz), 3.89-3.95(m, 1H, -OCH2, J = 4 Hz), 4.09-4.19(m, 2H, -OCH2, J = 4 Hz), 4.79-4.85(d, 1H, -CH, 2JHP = 24 Hz), 6.57-8.08(m, Ar-H); 13C NMR (100 MHz, CDCl3 ):δ (ppm):16.15 (d, 3Jcp = 6.0 Hz, -CH3-P ),16.42(d, 3Jcp = 6.0 Hz, -CH3-P),55.54(d, 1Jcp = 151 Hz,-CH-P),63.33(d, 2Jcp = 7.0 Hz, -OCH2-P),63.88(d, 2Jcp = 7.0 Hz, -OCH2-P), 112.43, 126.08, 127.68, 127.74, 128.51, 128.55, 128.91, 128.93, 139.04 for aromatic carbon, 134.51(d, 2Jcp = 3.00 Hz , Ar-P), 151.78(d, 3Jcp = 13.00 Hz, Ar-P);DEPT 135 NMR:δ(ppm):63.32(d, 2Jcp =7.0 Hz, -OCH2-P), 63.88(d, 2Jcp = 7.0 Hz, -OCH2-P).

Table 4: Multicomponent synthesis of α-aminophosphonates

Entry Aldehyde Amine Product Time min. Yield %
   a image image image 22 90
b image image image 18 92
c image image image 30 89
d image image image   22 91
e image image image 25 90
f image image image 20 93
g image image image 23 92
h image image image 20 92
I image image image 22 91
j image image image 15 94
k image image image 23 89
l image image image 24 91
m image image image 25 90
n image image image 34 91
o image image image 22 92
p image image image 29 91
q image image image 27 89
r image image image 33 90
s image image image 53 90
t image image image 17 91
u image image image 18 91
v image image image 21 92

Reaction conditions: Anisaldehyde (1mmol); aniline (1mmol); diethylphosphite (1mmol), solvent free, EPZGR catalyst 20mg, room temperature.

Conclusion

A convenient methodology for the synthesis of α –aminophosphonates derivatives is demonstrated employing EPZG a green, efficient and Lewis acid catalyst promoter. Solvent free and room temperature makes this protocol green one.

References

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