One-pot facile synthesis of novel 1,2,3-triazole-appended α-aminophosphonates

Article abstract of DOI:10.1007/s13738-018-1571-0

Abstract: New α-aminophosphonates bearing 1,2,3-triazolyl moiety were easily synthesized by one-pot reaction of 1-aryl-1H-1,2,3-triazole-4-carbaldehydes, anilines and trimethyl phosphite in good to excellent yields. All the synthesized compounds were char

Full text of DOI:10.1007/s13738-018-1571-0

Journal of the Iranian Chemical Society
https://doi.org/10.1007/s13738-018-1571-0
ORIGINAL PAPER
One-pot facile synthesis of novel 1,2,3-triazole-appended
α-aminophosphonates
Ashruba B. Danne1 · Satish V. Akolkar1 · Tejshri R. Deshmukh1 · Madiha M. Siddiqui1 · Bapurao B. Shingate1
Received: 5 September 2018 / Accepted: 6 December 2018
© Iranian Chemical Society 2018
Abstract
New α-aminophosphonates bearing 1,2,3-triazolyl moiety were easily synthesized by one-pot reaction of 1-aryl-1H-1,2,3-
triazole-4-carbaldehydes, anilines and trimethyl phosphite in good to excellent yields. All the synthesized compounds were
characterized by IR, 1H NMR and 13C NMR analysis. These novel 1,2,3-triazole-incorporated α-aminophosphonates may
be potential biological compounds due to the presence of both important moieties, 1,2,3-triazole and aminophosphonates.
Graphical abstract
Keywords 1,2,3-Triazole · α-Aminophosphonate · Multicomponent reaction · C–P bond formation
Introduction
special place among medicinally active products. The devel-
opment of a simple and efficient synthesis of compounds
incorporating heterocyclic ring has given a new dimension
to the drug discovery and development.
The design and development of new synthetic strategies
leading to diversely functionalized structures, which incor-
porates various active pharmacophores in a single molecu-
lar motif, have attracted great attention in synthetic organic
chemistry. In particular, heterocyclic compounds hold a
The term click chemistry which was hosted by Sharp-
less group is a cycloaddition reaction between alkyne and
azide catalyzed by Cu(I), and it selectively gives 1, 4-dis-
ubstituted 1,2,3-triazoles [1–6]. The 1,2,3-triazole ring
has great importance in medicinal chemistry [7–9]. The
1,2,3-triazole containing drugs, 5-amino-1-(3,5-dichloro-
4-(4-chlorobenzoyl)benzyl)-1H-1,2,3-triazole-4-carbox-
amide (CAI), cefatrizine and tazobactam are available in
the market (Fig. 1). The 1,2,3-triazole is an bioisostere of
amide [10] and also displays various biological activities
including α-glucosidases inhibitors [11], anticancer [12],
Electronic supplementary material The online version of this
article (https://doi.org/10.1007/s13738-018-1571-0) contains
supplementary material, which is available to authorized users.
* Bapurao B. Shingate
bapushingate@gmail.com
1
Department of Chemistry, Dr. Babasaheb Ambedkar
Marathwada University, Aurangabad 431 004, India
Vol.:(0123456789)
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Journal of the Iranian Chemical Society
Fig. 1 Structures of 1,2,3-triazole containing drugs
anti-inflammatory, anti-nociceptive [13], antifungal [14],
antibacterial [15] and antitubercular activities [16].
representative structures of α-aminophosphonate group
appended on heterocyclic skeleton are shown in Fig. 2.
A literature survey reveals that an extensive work was
done on the synthesis of α-aminophosphonates using a vari-
ety of catalysts such as LiClO4 [37–39], (LiClO4, TsOH)
[40], MoO2Cl2 [41], GaI3 [42], Mg(ClO4)2 [43], solvate
ionic liquid [44], nano-magnetic sulfated zirconia (Fe3O4@
ZrO2/SO42−) [45], Yb(OTf)3 [46], HfCl4 [47], SiO2-ZnBr2
[48], lanthanide triflate [49], ytterbium perfluorooctanoate
[50], SmI2 [51], TaCl5–SiO2 [52], BiCl3 [53], FeCl3 [54],
[CpRu(PPh3)2Cl] [55], camphor sulfonic acid [56] and
1-hexanesulphonic acid sodium salt [57].
Organophosphorous compounds have found a wide range
of applications in the agriculture, organic and medicinal
chemistry owing to their biological and pharmacologi-
cal properties as well as synthetic intermediates [17]. The
α-aminophosphonates are a well-known privileged structure
and have a wide range of applications in medicinal chemistry
[18–22] and are structural analogues of amino acids [18,
19]. The α-aminophosphonates possess a wide spectrum of
biological activities including antifungal [23], antimicrobial
[24], antiviral [25, 26], anticancer [27], anti-inflammatory
[28] and antiproliferative activities [29]. The heterocyclic
ring containing α-aminophosphonates displays various bio-
logical activities [18, 19, 30–33]. Furthermore, there are
some reports on the synthesis of β-aminophosphonates,
phosphinates [34], α-aminophosphonic acids [35] and the
biological activity of aminophosphonic acids [36]. The
In view of the above and continuation of research pro-
gram on chemistry and biology of 1,2,3-triazole contain-
ing compounds [58–66], herein, we would like to report
about the synthesis of new 1,2,3-triazole-appended
α-aminophosphonates using the molecular hybridization
approach.
Fig. 2 Representative structures of α-aminophosphonate conjugated with heterocycles
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Journal of the Iranian Chemical Society
1H), 7.73 (d, J = 6 Hz, 2H), 7.51–7.43 (m, 3H), 6.83 (s,
1H), 6.78–6.75 (m, 2H), 5.16 (dd, J = 22 and 8 Hz, 1H),
4.70 (s, 1H), 3.89 (d, J = 10 Hz, 3H), 3.74 (d, J = 10 Hz,
3H). 13C NMR (50 MHz, CDCl3) δ 143.9, 136.8, 129.8,
129.0, 120.7, 120.4, 114.3, 111.1, 110.7, 104.4, 103.8,
103.4, 54.5 (d, J = 7 Hz), 53.9 (d, J = 7.5 Hz), 48.8 (d,
J = 159.5 Hz).
Experimental
All the required reagents were purchased from Sigma-
Aldrich, Alfa Aesar, Spectrochem and used without puri-
fication. Melting points were obtained on open capillary
electrothermal apparatus and are uncorrected. Infrared (IR)
spectra were measured using Alpha Bruker FT-IR spectrom-
eter. The compounds were confirmed by NMR on a Bruker
Avance 400 and 200 MHz spectrometer. The compounds
were solubilized in CDCl3 and the TMS used as internal
standard. The DEPT experiment was used for the assignment
of the 13C signals. Multiplicity of the signals is shown as
singlet (s), doublet (d), triplet (t), quartet (q), multiplet (m),
doublet of doublet (dd) and coupling constant J are given in
Hz. The HRMS spectra were recorded under electrospray
ionization ESI HRMS.
Dimethyl (((4‑methoxyphenyl)amino)
(1‑phenyl‑1H‑1,2,3‑triazol‑4‑yl)methyl)phosphonate
(14f)
IR νmax cm−1: 3301, 1592, 1505, 1456, 1229, 1176, 1028,
1
826, 754, 682. H NMR (400 MHz, CDCl3) δ 8.07 (s,
1H), 7.69 (d, J = 8 Hz, 2H), 7.49 (t, J = 8 Hz, 2H), 7.41
(t, J=8 Hz, 1H), 6.74 (m, 4H), 5.14 (dd, J=24 and 8 Hz,
1H), 4.49 (t, J=8 Hz, 1H), 3.87 (d, J=12 Hz, 3H), 3.73 (d,
J=12 Hz, 3H), 3.71 (s, 3H). 13C NMR (100 MHz, CDCl3) δ
153.3, 144.5, 139.7, 136.8, 129.7, 128.8, 120.7, 120.4, 115.7,
114.8, 55.6, 54.4 (d, J=7.0 Hz), 53.8 (d, J=7.0 Hz), 49.6
(d, J=159 Hz). HRMS, calculated mass for C18H22N4O4P
(M+H)+:389.1379 and found: 389.1386.
General procedure for the preparation
of 1,2,3‑triazole‑appended α‑aminophosphonates
14a‑z
In a round-bottom flask equipped with a magnetic stirring
bar, a mixture of 1-aryl-1H-1,2,3-triazole-4-carbaldehydes
(0.5 mmol) and anilines (0.5 mmol) in methanol–acetic acid
was stirred, once the formation of Schiff’s base takes place,
trimethyl phosphite (0.5 mmol) was added to the reaction
mixture and stirred for 1.5–3 h at room temperature till
completion of the reaction. The progress of reaction was
monitored by TLC. After completion of the reaction, the
resulting mixture was poured on 50 mL ice water to obtain
solid, filtered, dried and recrystallized by aqueous ethanol
to get α-aminophosphonates.
Dimethyl (((2,4‑difluorophenyl)amino)
(1‑(2‑methoxyphenyl)‑1H‑1,2,3‑triazol‑4‑yl)methyl)
phosphonate (14g)
IR νmax cm−1: 3283, 1610, 1509, 1459, 1285, 1243, 1023,
1
957, 750. H NMR (400 MHz, CDCl3) δ 8.23 (s, 1H),
7.78 (d, J=4 Hz, 1H), 7.41 (s, 1H), 7.07 (t, J=8 Hz, 2H),
6.83–6.72 (m, 3H), 5.16 (dd, J=20 and 8 Hz, 1H), 4.70 (s,
1H), 3.87 (d, J=12 Hz, 3H), 3.85 (s, 3H), 3.72 (d, J=12 Hz,
3H). 13C NMR (100 MHz, CDCl3) δ 150.9, 142.3, 130.3,
126.0, 125.3, 124.8, 121.2, 114.6, 112.2, 110.9, 110.7,
103.9, 103.7, 103.5, 55.9, 54.3 (d, J = 7 Hz), 53.9 (d,
J=7 Hz), 49.0 (d, J=159 Hz).
Dimethyl ((1‑phenyl‑1H‑1,2,3‑triazol‑4‑yl)
(p‑tolylamino)methyl)phosphonate (14b)
IR νmax cm−1: 3309, 1611, 1514, 1449, 1236, 1039, 822,
756, 689. 1H NMR (200 MHz, CDCl3) δ 8.07 (s, 1H), 7.68
(s, 2H), 7.49–7.45 (m, 3H), 6.98 (d, J=6 Hz, 2H), 6.68 (d,
J=6 Hz, 2H), 5.20 (d, J=22 Hz, 1H), 4.62 (s, 1H), 3.87 (d,
J = 12 Hz, 3H), 3.73 (d, J = 12 Hz, 3H), 2.21 (s, 3H). 13C
NMR (50 MHz, CDCl3) δ 143.5, 143.3, 136.9, 129.9, 129.7,
128.9, 128.6, 120.8, 120.4, 114.3, 54.4 (d, J=7 Hz), 53.9 (d,
J=7 Hz), 48.8 (d, J=158.5 Hz), 20.4.
Dimethyl (((4‑chlorophenyl)amino)
(1‑(2‑methoxyphenyl)‑1H‑1,2,3‑triazol‑4‑yl)methyl)
phosphonate (14h)
IR νmax cm−1: 3292, 1593, 1532, 1490, 1240, 1174, 1025,
1
824, 751, 639. H NMR (400 MHz, CDCl3) δ 8.19 (s,
1H), 7.77 (dd, J=8, 4 Hz, 1H), 7.41 (t, J=8 Hz, 1H), 7.12
(d, J = 8 Hz, 2H), 7.09–7.04 (m, 2H), 6.70 (d, J = 12 Hz,
2H), 5.16 (dd, J=24 and 8 Hz, 1H), 4.75 (s, 1H), 3.84 (d,
J = 12 Hz, 3H), 3.82 (s, 3H), 3.71 (d, J= 12 Hz, 3H). 13C
NMR (100 MHz, CDCl3) δ 151.0, 144.6, 142.4, 130.2,
129.1, 126.2, 125.3, 124.8, 123.8, 121.2, 115.4, 112.3, 55.9,
54.2 (d, J=7 Hz), 53.9 (d, J=7 Hz), 48.9 (d, J=159 Hz).
Dimethyl (((2,4‑difluorophenyl)amino)
(1‑phenyl‑1H‑1,2,3‑triazol‑4‑yl)methyl)
phosphonate (14e)
IR νmax cm−1: 3296, 1599, 1510, 1441, 1248, 1204,
1
1041, 835, 755. H NMR (200 MHz, CDCl3) δ 8.12 (s,
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Journal of the Iranian Chemical Society
Dimethyl ((1‑(2‑methoxyphenyl)‑1H‑1,2,3‑triazol‑
4‑yl)(p‑tolylamino)methyl)phosphonate (14i)
Dimethyl ((1‑(4‑nitrophenyl)‑1H‑1,2,3‑triazol‑4‑yl)
(p‑tolylamino)methyl)phosphonate (14s)
IR νmax cm−1: 3302, 1605, 1508, 1463, 1242, 1174, 1028,
820, 748, 661. 1H NMR (400 MHz, CDCl3) δ 8.19 (s, 1H),
7.77 (d, J=8 Hz, 1H), 7.39 (t, J=8 Hz, 1H), 7.09–7.03 (m,
2H), 6.98 (d, J=8 Hz, 2H), 6.69 (d, J=8 Hz, 2H), 5.19 (dd,
J=20 and 8 Hz, 1H), 4.58 (s, 1H), 3.85 (d, J=8 Hz, 3H),
3.82 (s, 3H), 3.71 (d, J=12 Hz, 3H), 2.21 (s, 3H). 13C NMR
(100 MHz, CDCl3) δ 150.9, 143.7, 142.9, 130.1, 129.8,
128.3, 126.2, 125.3, 124.8, 121.2, 114.4, 112.2, 55.9, 54.2
(d, J=6 Hz), 53.9 (d, J=8 Hz), 49.0 (d, J=159 Hz), 20.4.
IR νmax cm−1: 3288, 1602, 1521, 1444, 1334, 1239, 1172,
1
1014, 843, 797, 745, 676. H NMR (400 MHz, CDCl3)
δ 8.36 (d, J = 8 Hz, 2H), 8.23 (s, 1H), 7.90 (d, J = 8 Hz,
2H), 6.97 (d, J = 12 Hz, 2H), 6.67 (d, J = 8 Hz, 2H), 5.23
(dd, J = 24 and 8 Hz, 1H), 4.74 (t, J = 8.0 Hz, 1H), 3.89
(d, J = 12 Hz, 3H), 3.77 (d, J = 12 Hz, 3H), 2.20 (s, 3H).
13C NMR (100 MHz, CDCl3) δ 147.2, 145.7, 143.3, 140.9,
129.9, 128.8, 125.4, 120.7, 120.4, 114.2, 54.5 (d, J=7 Hz),
53.9 (d, J=7 Hz), 48.6 (d, J=158 Hz), 20.4. HRMS, calcu-
lated mass for C18H21N5O5P (M+H)+: 418.1280 and found:
418.1283.
Dimethyl (((3‑bromophenyl)amino)
(1‑(2‑methoxyphenyl)‑1H‑1,2,3‑triazol‑4 yl)methyl)
phosphonate (14j)
Dimethyl ((1‑(3‑chlorophenyl)‑1H‑1,2,3‑triazol‑4‑yl)
((4‑methoxyphenyl)amino)methyl)phosphonate
(14v)
IR νmax cm−1: 3289, 1588, 1470, 1231, 1175, 1028, 864,
826, 758, 667. 1H NMR (400 MHz, CDCl3) δ 8.19 (s, 1H),
7.75 (d, J=8 Hz, 1H), 7.38 (t, J=8 Hz, 1H), 7.08–6.97 (m,
3H), 6.90 (s, 1H), 6.84 (d, J=8 Hz, 1H), 6.67 (d, J=8 Hz,
1H), 5.15 (dd, J=24 and 4 Hz, 1H), 4.91 (s, 1H), 3.82 (d,
J=8 Hz, 3H), 3.79 (s, 3H), 3.69 (d, J=8 Hz, 3H). 13C NMR
(100 MHz, CDCl3) δ 151.0, 147.5, 142.2, 130.7, 130.3,
126.1, 125.4, 124.9, 123.2, 121.9, 121.3, 116.9, 112.7,
112.3, 56.0, 54.3 (d, J=7 Hz), 54.0 (d, J=7 Hz), 48.5 (d,
J=159 Hz).
IR νmax cm−1: 3328, 1592, 1510, 1234, 1177, 1038, 831,
776, 674. 1H NMR (400 MHz, CDCl3) δ 8.09 (s, 1H), 7.74
(s, 1H), 7.59 (d, J=8 Hz, 1H), 7.42–7.39 (m, 2H), 6.73 (q,
J=8 Hz, 4H), 5.14 (dd, J=24 and 8 Hz, 1H), 4.53 (s, 1H),
3.88 (d, J=8 Hz, 3H), 3.74 (d, J=12 Hz, 3H), 3.71 (s, 3H).
13C NMR (100 MHz, CDCl3) δ 153.3, 144.9, 139.7, 139.6,
137.6, 135.5, 130.8, 128.9, 120.6, 118.3, 115.7, 114.8, 55.6,
54.4 (d, J=7 Hz), 53.8 (d, J=7 Hz), 49.5 (d, J=159 Hz).
Dimethyl ((1‑(4‑methoxyphenyl)‑1H‑1,2,3‑triazol‑
4‑yl)(phenylamino)methyl)phosphonate (14m)
Dimethyl ((1‑(3‑chlorophenyl)‑1H‑1,2,3‑triazol‑4‑yl)
((4‑chlorophenyl)amino)methyl)phosphonate (14w)
IR νmax cm−1: 3291, 1599, 1497, 1461, 1215, 1178, 1031,
988, 830, 749, 696. 1H NMR (400 MHz, CDCl3) δ 8.06 (s,
1H), 7.56 (d, J=8 Hz, 2H), 7.17 (t, J=8 Hz, 2H), 6.96 (d,
J=12 Hz, 2H), 6.79–6.76 (m, 3H), 5.26 (d, J=24 Hz, 1H),
4.95 (s, 1H), 3.87 (d, J=12 Hz, 3H), 3.83 (s, 3H), 3.74 (d,
J=8 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 159.8, 145.9,
144.2, 130.3, 129.3, 121.9, 120.9, 119.0, 114.7, 114.0, 55.6,
54.3 (d, J=7 Hz), 53.9 (d, J=7 Hz), 48.4 (d, J=159 Hz).
IR νmax cm−1: 3304, 1592, 1493, 1239, 1035, 829, 776,
1
646. H NMR (400 MHz, CDCl3) δ 8.12 (s, 1H), 7.73 (s,
1H), 7.57 (d, J = 8 Hz, 1H), 7.44–7.40 (m, 2H), 7.10 (d,
J=8 Hz, 2H), 6.68 (d, J =8 Hz, 2H), 5.18 (dd, J =20 and
8 Hz, 1H), 4.94 (t, J=8 Hz, 1H), 3.87 (d, J=8 Hz, 3H), 3.74
(d, J=12 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 144.4,
144.3, 137.6, 135.6, 130.8, 129.2, 128.9, 123.9, 120.7,
120.6, 118.3, 115.2, 54.4 (d, J=7.0 Hz), 53.9 (d, J=8 Hz),
48.5 (d, J=158 Hz).
Dimethyl (((4‑chlorophenyl)amino)
(1‑(4‑nitrophenyl)‑1H‑1,2,3‑triazol‑4‑yl)methyl)
phosphonate (14r)
Dimethyl ((1‑(3‑chlorophenyl)‑1H‑1,2,3‑triazol‑4‑yl)
(p‑tolylamino)methyl)phosphonate (14x)
IR νmax cm−1: 3297, 1552, 1502, 1328, 1227, 1178, 1047,
IR νmax cm−1: 3323, 1593, 1514, 1490, 1242, 1040, 889,
779, 676. 1H NMR (400 MHz, CDCl3) δ 8.08 (s, 1H), 7.74
(s, 1H), 7.58 (d, J=8 Hz, 1H), 7.42–7.39 (m, 2H), 6.97 (d,
J=8 Hz, 2H), 6.67 (d, J =8 Hz, 2H), 5.20 (dd, J =20 and
8 Hz, 1H), 4.65 (t, J =8 Hz, 1H), 3.88 (d, J =12 Hz, 3H),
3.74 (d, J=8 Hz, 3H), 2.21 (s, 3H). 13C NMR (100 MHz,
CDCl3) δ 144.9, 143.4, 143.3, 137.7, 135.5, 130.8, 129.9,
128.9, 128.6, 120.6, 118.3, 114.2, 54.4 (d, J=7 Hz), 53.8
(d, J=7 Hz), 48.8 (d, J=158 Hz), 20.4.
1
1007, 833, 747. H NMR (400 MHz, CDCl3) δ 8.39 (d,
J=8.0 Hz, 2H), 8.21 (d, J=4 Hz, 1H), 7.94 (d, J=8.0 Hz,
2H), 7.12 (d, J = 8 Hz, 2H), 6.68 (d, J = 8 Hz, 2H), 5.18
(dd, J = 24 and 8 Hz, 1H), 4.81 (t, J= 8 Hz, 1H), 3.89 (d,
J=12 Hz, 3H), 3.76 (d, J=12 Hz, 3H). 13C NMR (100 MHz,
CDCl3) δ 147.4, 145.2, 144.3, 140.9, 129.4, 125.6, 124.3,
121.6, 120.5, 115.3, 54.6 (d, J=7 Hz), 54.0 (d, J=7 Hz),
48.5 (d, J=158 Hz).
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Journal of the Iranian Chemical Society
and triazole-biscoumarin conjugates as antitubercu-
lar agents. Keeping in mind all the above, we have
planned to synthesize a novel 1,2,3-triazole-appended
α-aminophosphonates via MCR approach. The acid-cata-
lyzed one-pot multicomponent reaction between aldehyde,
amine and trialkyl phosphite forms α-aminophosphonates.
The first step involved in this reaction is the formation
of an imine intermediate followed by an addition of
the trialkyl phosphite across the C=N double bond and
finally the C–P and C–N bond formation takes place.
The most important application of the synthesis of
α-aminophosphonate involves the formation of the C–P
and C–N bond. Recently, Maghsoodlou et al. reported
[76] the synthesis of α-aminophosphonates using ace-
tic acid as a medium as well as a catalyst. In our present
study, we have synthesized new 1,2,3-triazole-appended
α-aminophosphonates 14a–z using one-pot three com-
ponent reaction between 1-aryl-1H-1,2,3-triazole-4-car-
baldehydes 11, anilines 12 to form Schiff’s base and then
trimethyl phosphite was added in methanol–acetic acid at
room temperature in excellent yields (Scheme 1). In this
study, we have reduced the concentration of acetic acid
and added methanol as a co-solvent.
Dimethyl ((1‑(4‑chlorophenyl)‑1H‑1,2,3‑triazol‑4‑yl)
((4‑chlorophenyl)amino)methyl)phosphonate (14z)
IR νmax cm−1: 3280, 1591, 1489, 1313, 1237, 1036, 818,
1
740. H NMR (400 MHz, CDCl3) δ 8.11 (s, 1H), 7.61 (d,
J=8 Hz, 2H), 7.45 (d, J=8 Hz, 2H), 7.10 (d, J=8 Hz, 2H),
6.69 (d, J=8 Hz, 2H), 5.18 (dd, J=20 and 8 Hz, 1H), 5.00
(t, J=8 Hz, 1H), 3.87 (d, J=12 Hz, 3H), 3.74 (d, J=12 Hz,
3H). 13C NMR (100 MHz, CDCl3) δ 144.5, 144.4, 135.3,
134.8, 129.9, 129.3, 124.0, 121.6, 120.8, 115.3, 54.5 (d,
J=7 Hz), 54.0 (d, J=7 Hz), 48.6 (d, J=159 Hz).
Results and discussion
Chemistry
To optimize the best reaction condition for executing a one-
pot three component reaction for the preparation of new
triazole-appended α-aminophosphonates requires 1,2,3-tria-
zolyl aldehydes as a starting material. The 1-aryl-1H-1,2,3-
triazole-4-carbaldehydes were prepared from corresponding
commercially available anilines. Anilines, sodium nitrite
and hydrochloric acid were appropriately combined to form
corresponding diazonium salts, which were subsequently
converted into aromatic azides by adding the solution of
sodium azide. The synthesis of 1,2,3-triazoles involves the
1,3-dipolar cycloaddition (click reaction) between propargyl
alcohol and aromatic azides using t-butanol:H2O as solvent,
catalyzed by Cu(I) and provided only the 1,4-regioisomers
in good yields ranging from 60 to 86%. Triazolyl alcohols
were further oxidized to aldehydes using Collins reagent
CrO3:2Py in CH2Cl2 in 50–65% yields.
The structures of the newly synthesized 1,2,3-triazole-
appended α-aminophosphonates has been confirmed by
1
physical data and spectral analysis. In the H NMR spec-
trum of compound 14b, the doublet signal was observed for
chiral proton at δ 5.20 ppm. Singlet signal at δ 4.62 ppm was
observed for NH proton. The two doublet signals observed
at δ 3.73 and 3.87 ppm for two methoxy groups were
attached to phosphorus. The singlet signal at δ 8.07 ppm was
observed for triazolyl proton. In the 13C NMR spectrum of
14b, the peaks were observed at δ 53.9, 54.4 ppm due to the
two methoxy groups attached to phosphorus and a peak at
48.8 ppm due to methine carbon. The structures, yields and
melting points for all the newly synthesized 1,2,3-triazole-
appended α-aminophosphonates are given in Fig. 4.
The triazolyl aldehydes have many applications in syn-
thetic organic chemistry for the construction of diversely
functionalized bioactive molecules (Fig. 3). Boechat et al.
reported [67] the hydrazone 1 was derived from triazolyl
aldehyde and isonicotinic acid hydrazide and it displays
good antitubercular activity. Wang et al. constructed [68]
the molecules 2, 3 and evaluated for their anti-phytopath-
ogenic activity. The molecule 4 has been synthesized and
evaluated for their antifungal activity by Dai et al. [69].
The triazolyl nitrone 5 as anti-inflammatory and anticancer
agents was also reported [70]. The tuberculosis inhibitory
activity was reported [71] for the compound 6 and antifun-
gal activity for 7 [72]. Ismail et al. combined two heterocy-
cles in single molecule 8 and it was evaluated as immune
potentiator [73]. The molecule 9 [74] were reported for
their alpha-glycosidases activity and 10 [75] were reported
in the literature for their antimicrobial activity.
Conclusion
In summary, we have demonstrated a library of novel
1,2,3-triazole-incorporated α-aminophosphonates from the
corresponding triazolyl aldehydes, anilines and trimethyl
phosphite in excellent yields for the first time. The synthe-
sized molecules having two pharmacophoric units, likely
1,2,3-triazole and α-aminophosphonates may display better
biological activities.
Recently, we have reported [58, 59] the use of triazolyl
aldehydes for the synthesis of triazole-diindolylmethane
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Journal of the Iranian Chemical Society
Fig. 3 Applications of
1,2,3-triazolyl aldehydes for the
synthesis of bioactive molecules
Scheme 1 Synthesis of 1,2,3-triazole-appended α-aminophosphonate hybrids
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Journal of the Iranian Chemical Society
Fig. 4 The structures, yield and
melting points for 1,2,3-triazole-
appended α-aminophosphonate
derivatives
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Journal of the Iranian Chemical Society
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Acknowledgements The authors A.B.D. and S.V.A. are very much
grateful to the University Grants Commission (UGC) and Council of
Scientific and Industrial Research (CSIR), New Delhi, respectively for
the award of research fellowship. The authors are also thankful to the
Department of Chemistry, Dr. Babasaheb Ambedkar Marathwada Uni-
versity, Aurangabad-431 004, India for providing laboratory facilities.
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