An Elegant Synthesis of a New Class of 1-(Substituted)-1H-1,2,3-triazol-4-yl)methyl)diphenylphosphineoxides by Microwave Irradiation

Article abstract of DOI:10.1002/jhet.2297

A simple and efficient one-pot microwave-assisted click formation of 1-(substituted)-1H-1,2,3-triazol-4-yl)methyl)diphenylphosphineoxide derivatives via Huisgen regioselective [3+2]-cycloaddition of an in situ generated organic azides and diphenyl(prop-2-yn-1-yl)phosphine oxide in highly polar DMSO-H₂O medium. This synthetic protocol is mild, requires shorter reaction time, and afforded products in excellent yields with high regioselectivity.

Full text of DOI:10.1002/jhet.2297

1876
An Elegant Synthesis of a New Class of 1-(Substituted)-1H-1,2,3-triazol-4-yl)
Vol 52
methyl)diphenylphosphineoxides by Microwave Irradiation
Radha Rani Chinthaparthi,a Chandra Sekhar Reddy Gangireddy,a,b Madhu Kumar Reddy Kandula,a
a
a
*
Satheesh Krishna Balam, and Suresh Reddy Cirandur
aDepartment of Chemistry, Sri Venkateswara University, Tirupati, 517 502, India
bDepartment of Chemistry, Sri Venkateswara College of Engineering, Karakambadi Road, Tirupati, 517 507, India
*
E-mail:csrsvu@gmail.com
Received April 23, 2014
DOI 10.1002/jhet.2297
Published online 16 December 2014 in Wiley Online Library (wileyonlinelibrary.com).
A simple and efficient one-pot microwave-assisted click formation of 1-(substituted)-1H-1,2,3-triazol-4-
yl)methyl)diphenylphosphineoxide derivatives via Huisgen regioselective [3+2]-cycloaddition of an in situ
generated organic azides and diphenyl(prop-2-yn-1-yl)phosphine oxide in highly polar DMSO-H2O
medium. This synthetic protocol is mild, requires shorter reaction time, and afforded products in excellent
yields with high regioselectivity.
J. Heterocyclic Chem., 52, 1876 (2015).
INTRODUCTION
RESULTS AND DISCUSSION
In the recent years, researchers focused more attention
on the drug design with 1,2,3-triazole ring [1–5]. Several
methodologies have been developed for their synthesis
[6,7]. The Cu(I) catalyzed click [3+2]-cycloaddition reac-
tion [8,9] of terminal alkynes and azides gained merit for
the 1,2,3-triazole synthesis because of its remarkable effi-
ciency and selectivity [10–12]. Organophosphorus com-
pounds (OPCs) possess wide spectrum of biological
properties particularly for their action on neuro transmis-
sion system and inhibition of the functioning of acetyl cho-
linesterase [13–17].
A logical connection of 1,2,3-triazole moiety with
an already bioactive organophosphorus compounds
through the click synthesis may further enhance the
medicinal activity of the resulting molecules, which
possess good polar hosting cites for effective chelation
with the metal/metal complexes in the bio-fluids in the
living system [18].
The diphenyl(prop-2-yn-1-yl)phosphine oxide (4) precursor
was prepared by nucleophilic addition of triphenylphosphine
(1) and propargylbromide (2) in refluxing toluene. The
stable triphenyl(prop-2yn-1-yl)phosphonium bromide salt
(3) on base hydrolysis afforded phosphine oxide (4) in
excellent yield (97.6%), (Scheme 1) [24,25].
Synthesis of the titled compounds (6a–o) was accom-
plished by Huisgen’s click reaction after optimizing its
reaction conditions. Several experimental conditions were
tried. 1,3-Cycloaddition under thermal condition was per-
formed between 4 and benzyl azide (5a′) generated in situ
from NaN3 and benzyl bromide (5a) in the presence of
CuBr(PPh3)3 as catalyst in DMSO at room temperature
for 30 min (Scheme 2). We observed only 61.1% of
product yield (6a). When the reaction was performed at
varying temperatures from 60 to 180°C, product yields
increased from moderate to higher percentage. But the max-
imum yield (93.3%) was obtained at 180°C for 150 min
reaction time (Table 1, entry 8).
In continuation of our work on green synthetic methodol-
ogies of organophosphorus heterocycles [13,19–21], synthe-
sis of title compounds was accomplished in a single step
one-pot multicomponent by microwave irradiation (MWI)
reaction at enhanced rate with high product yields [22,23].
To increase the product yield further and decrease the
reaction time, we applied the microwave energy instead
of the thermal energy for this reaction at 40°C for 5 min
and obtained 68.7% product yield (Table 1, entry 2). To
© 2014 HeteroCorporation

Microwave-assisted Click Generation of 1,2,3-Triazol Containing Diphenylphosphine
Oxides
November 2015
1877
Scheme 1. Synthesis of diphenyl(prop-2-yn-1-yl)phosphine oxide (4).
Scheme 2. Regioselective preparation of ((1-benzyl-1H-1,2,3-triazol-4-yl)methyl)diphenylphosphine oxide (6a).
Table 1
Huisgen 1,3-dipolar cycloaddition of CuAAC of the model click ingredientsa.
Conventional heating
Time (min)
Microwave heating
Entry
Temp. (°C)
Yieldb (%)
Power (W)
Temp. (°C)
Time (min)
Yieldb (%)
1
2
3
4
5
6
7
8
r.t.
60
80
100
100
100
140
180
30
60
60
60
90
120
120
150
61.1
65.0
74.5
78.2
86.9
89.7
91.4
93.3
---
---
40
50
50
70
80
80
100
---
5
5
6
6
7
8
10
---
140
210
210
280
280
280
280
68.7
74.8
77.7
90.1
97.4
97.6
97.9
aReaction conditions of CuAAC of the model click ingredients are 4, NaN3 and 5a using 0.5 mol% of CuBr(PPh3)3 as catalyst in 1:1.2:1 mol ratio,
bIsolated yield.
Table 2
Effect of the solvent on Huisgen 1,3-dipolar cycloaddition of CuAAC of the model click ingredients (6a)a.
Yieldb (%)
Entry
Solvent
Thermal condition
Microwave condition
1
2
3
4
5
6
7
8
Carbon tetrachloride
Toluene
Dichloromethane
Tetrahydrofuran
Chloroform
Methanol
Ethanol
Acetonitrile
Dimethyl formamide
Dimethyl sulfoxide
Water
Water–DMSO
Solvent-free
55.3
58.4
56.2
59.8
60.5
72.7
72.9
80.7
88.8
90.2
93.1
95.2
81.2
58.3
63.7
65.8
69.3
72.1
81.7
82.2
86.3
92.8
95.9
97.6
98.7
89.5
9
10
11
12
13
aReaction conditions: 4, NaN3 and 5a using 0.5 mol% of CuBr(PPh3)3 as catalyst in 1:1.2:1mol ratio. All the reactions in con-
ventional and microwave (at 280 W) conditions are made at 180 and 100°C for 150 and 10-min reaction time, respectively,
bIsolated yield.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

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R. R. Chinthaparthi, C. S. R. Gangireddy, M. K. R. Kandula, S. K. Balam, and S. R. Cirandur
Vol 52
Table 3
Microwave assisted CuAAC synthesis of 6a–o via Scheme 3.
Entry
Product
Temp. (°C)
Time (min)
Yielda (%)
1
2
3
4
5
6
7
8
6a
6b
6c
6d
6e
6f
6g
6h
6i
6j
6k
6l
6m
6n
6o
80
80
80
10
10
10
11
11
11
11
11
12
12
12
12
13
14
14
99.2
99.2
99.3
97.0
96.0
95.2
95.0
95.1
95.0
95.0
97.4
98.3
95.0
91.0
90.0
90
100
110
110
110
110
110
110
110
110
120
120
9
10
11
12
13
14
15
Figure 1. Optimization of various solvents for the model reaction in ther-
mal and microwave conditions. [Color figure can be viewed in the online
issue, which is available at wileyonlinelibrary.com.]
aIsolated yield.
identify the best microwave irradiation reaction conditions,
we performed this reaction with 0.5 mol% of the catalyst at
various temperatures, different microwave power and
reaction times (Table 1, entries 3–8). It is observed that,
increase of temperature, MW power and reaction time
has significant effect on the rate of the reaction and product
yield (Table 1, entry 8).
The effect of the solvent on this reaction also studied with
0.5 mol% of CuBr(PPh3)3 catalyst at 180°C for 150 min and
100°C for 10 min in conventional and MWI conditions re-
spectively using different solvents (Table 2, entries 1–12).
The results showed (Fig. 1) that lower product yields are
observed in non-polar/less polar solvents (Table 2, entries
1–5), whereas the product yield increased with the increase
of solvent polarity (Table 2, entries 6–11). This might be
because that polar solvents undergo higher dipole rotation
under microwave irradiation and generates abnormal heat
energy that effectively converted the reactants to the
products in higher yields at fast rate (Table 2, entry 12).
But the same reaction under solvent-free conditions
afforded only lower product yield (Table 2, entry 13).
Finally, the established optimum experimental condi-
tions for this reaction are high polar solvent medium of
DMSO/H2O (1:1) and 280 W of microwave irradiation at
100°C for 10 min (Table 2, entry 12) using 0.5 mol% of
CuBr(PPh3)3 as catalyst. Synthesis of all the other titled
1,2,3-triazole diphenylphosphine oxides (6b–o) containing
different functionalised alkyl/aryl moieties were accom-
plished by following this procedure (Scheme 3) and
achieved excellent yields (Table 3).
It is interesting to find decrease in the yields with increase
in the alkyl chain of the halide (Table 3, entries 14, 15). This
Scheme 3. Microwave-assisted CuAAC synthesis of 1-(substituted)-1H-1,2,3-triazol-4-yl)methyl)diphenylphosphine oxides (6b–o).
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Microwave-assisted Click Generation of 1,2,3-Triazol Containing
Diphenylphosphine Oxides
November 2015
1879
Scheme 4. Mechanism of microwave-assisted CuAAC synthesis of 6a–o. [Color figure can be viewed in the online issue, which is available at
wileyonlinelibrary.com.]
Merck (Mumbai, India), Lancaster Chemical (Mumbai, India),
and Sigma–Aldrich (Hyderabad, India) were used as received.
Melting points were determined in the Guna Digital melting
point apparatus (Guna Enterprises, Chennai, India) using a
calibrated thermometer. All the reactions were carried out in air
in technical solvents without excluding moisture or oxygen.
Column/TLC chromatography was performed on silica gel
using UV light and iodine to visualize the products. IR spectra
were recorded on FTIR spectrophotometer (IR-Prestige 21,
Shimadzu Corporation, Japan) using KBr optics. 1H, 13C, and
31P NMR spectra were recorded at room temperature in CDCl3
on a Varian 400-MHz NMR spectrometer operating at 400, 100,
and 161.89 MHz, respectively, at the Pusan National University,
might be due to the hydrophobicity of longer hydrocarbon
chain in the halide (5b–o). Aromatic halides afforded higher
product yields irrespective of the electronic nature of
substituents. Steric repulsion of the bulky groups closer to
azide functionality resulted in lesser product yields (Table 3,
entries 6 and 8–10).
This reaction proceeds with the initial formation of a CuBr
(PPh3)3 acetylide π-complex (I) [26–28]. Substitution of its
terminal alkyne hydrogen with copper leads to corres-
ponding σ-acetylide Cu(I) complex (II). Addition of 5a′–o′,
which are formed in situ from 5a–o and sodium azide to II
leads to Cu(0) complex IV through the intermediate III in
stepwise mechanism according to the density functional
theory calculations [29]. Cleavage of allene double bond and
rearrangement of IV leads to compound V, which on acidifi-
cation leads to formation of 6a–o (Scheme 4). In this process,
the CuBr(PPh3)3 gets eliminated in pure form and as such it
could continue to play its role in the process again and again.
1
Pusan, Republic of Korea. The H and 13C chemical shifts (δ)
are reported in ppm with respect to TMS and those of 31P in
85% H3PO4. Mass spectra were recorded on a Jeol JMS-700
mass spectrometer at Pukyong National University, Busan,
Republic of Korea. Elemental analyses were performed on a
Thermo Finnigan instrument at the University of Hyderabad,
India. All reported yields are isolated product yields, and in the
catalytic studies, the average yield of at least two runs is taken.
Synthesis of diphenyl(prop-2-yn-1-yl)phosphine oxide
CONCLUSIONS
(4).
Diphenyl(prop-2-yn-1-yl)phosphine oxide was prepared
[24,30] by Michaelis–Arbuzov reaction between triphenyl
phosphine (6.82 g, 0.026 mol) and propargyl bromide (3.77 g,
0.032 mol) in 10 mL of dry toluene, charged in to 250-mL round-
bottom flask (Scheme 1). The reaction mixture was then heated to
reflux at 110°C for 2 h and then cooled at room temperature. The
phosphonium salt (3) was obtained as white powdered. It was
filtered and washed several times with diethyl ether. The product
was taken in 100 mL of water and then refluxed half an hour. After
this, 60 mL of 2.77 M NaOH aqueous solution was added into the
dense suspension and gently refluxed for an additional 2 h. After
cooling, the mixture was extracted with dichloromethane and the
extractant was evaporated under vacuum after drying with
anhydrous sodium sulfate. The crud product was recrystallized from
hexane–diethyl ether to obtain the product as a white crystalline
solid, 6. About 10 g (97.6%); mp: 152–154°C, 31P-NMR
(162 MHz, CDCl3) δ = 22.22 ppm; 1H-NMR (400 MHz, CDCl3)
We have successfully developed a simple and effective
method for the preparation of 1-(substituted)-1H-1,2,3-
Triazol-4-yl)methyl)diphenylphosphineoxides (6a–o) by
regioselective [3+2]-cycloaddition of organic azides to ter-
minal alkynes with click chemistry using 280-W microwave
power at 100°C for 10 min in 1:1 DMSO/H2O medium in the
presence of 0.5 mol% of CuBr(PPh3)3 catalyst. The simplic-
ity and efficiency of this procedure allows it for a one-pot
three-component commercial preparation of a wide variety
of bio-active 1,2,3-triazole diphenylphosphine oxides.
EXPERIMENTAL
Materials and methods. All the chemicals/reagents, CuBr
(PPh3)3 catalyst and analytical grade solvents procured from
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

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R. R. Chinthaparthi, C. S. R. Gangireddy, M. K. R. Kandula, S. K. Balam, and S. R. Cirandur
Vol 52
δ =7.67–7.41 (m, 10H, Ar–H), 2.21–2.17 (dd, 2H, 2JPH = 12, 4 Hz,
P–CH2), 2.88 (s, 1H, C–HAlkyne) ppm; 13C-NMR (100.56 MHz,
CDCl3) δ = 53.5, 128.4, 128.5, 131.9, 132.0, 132.9, 133.5 ppm. MS
(70 eV): m/z= 240 (M+•). IR (KBR) vmax = 2299 (C–HAlkyne), 2933
and 2865 (C–H), 2217 (C–CAlkyne), 1264 (P¼O) cmꢀ1. Anal.
Calcd. for C15H13OP: C, 74.99; H, 5.45. Found: C, 74.90; H, 5.37.
((1-(4-Methoxybenzyl)-1H-1,2,3-triazol-4-yl)methyl)
diphenylphosphine oxide (6c). Yellow solid, mp: 165–167°C.
31P-NMR (CDCl3) δ [ppm]: 23.59; 1H-NMR (400 MHz, CDCl3)
δ [ppm]: 7.48–6.98 (14H, m, Ar–H), 8.27 (1H, s, N–CH¼), 5.43
2
(2H, d, JH-P = 6.54 Hz, P–CH2), 2.42 (3H, s, OCH3); 13C-NMR
(100.56 MHz, CDCl3) δ [ppm]: 136.3, 135.6, 134.3, 132.7,
131.5, 130.7, 129.5, 129.5, 127.4, 123.5, 59.5, 39.5, 56.6. MS
(M+•; m/z): 403. IR (KBR) (vmax cmꢀ1): 2938 and 2856 (C–H),
1620 (C¼N), 1446 (C–N), 1386, 1223 (P¼O), 1020, 971 (P–O),
731 (P–C). Anal. Calcd. for C23H22N3O2P: C, 68.48; H, 5.50, N,
10.42. Found: C, 68.40; H, 5.42; N, 10.35.
Synthesis
of
((1-benzyl-1H-1,2,3-triazol-4-yl)methyl)
diphenylphosphine oxide (6a). MWI method.
In a two-
necked round-bottom flask, fitted with air condenser and thermo
probe a mixture of 4 (0.5 mmol), 5a (0.5 mmol), CuBr(PPh3)3,
(2.3 mg, 0.5 mol%), and NaN3 (42 mg, 0.65 mmol) in water (5 mL)
and in DMSO (5 mL) were taken (Scheme 3). All the contents were
mixed thoroughly and exposed to MWI in CATA-4R—Scientific
Microwave oven at 40–100°C with 140–280 W at ambient pressure.
The reaction mixture was stirred continually during microwave
radiation to maintain the temperature homogeneously. After the
total consumption of the starting benzyl bromide in 5–10 min as
indicated by TLC, the solvents were removed in the rotary
evaporator, and the crud product obtained was washed thoroughly
with water to remove any azide residue. This crude product was
purified by column chromatography on 60–120 mesh silica gel
using ethyl acetate/hexane (1:3) as eluent, and the solvent was
evaporated in a rotary evaporator. This compound was further
recrystallized from ethyl acetate to afford pure 6a (Table 1).
Conventional method. The reactants were heated in an oil-
bath up to 180°C from room temperature (r.t.) for 30–150 min and
the workup and purification of products were carried out as
described in the MWI procedure.
((1-(4-Nitrobenzyl)-1H-1,2,3-triazol-4-yl)methyl)diphenylphosphine
oxide (6d).
Dark yellow solid, mp: 159–161°C, 31P-NMR
1
(CDCl3) δ [ppm]: 24.23; H-NMR (400 MHz, CDCl3) δ [ppm]:
7.69–7.18 (14H, m, Ar–H), 8.22 (1H, s, N–CH¼), 5.46 (2H, d,
2JH-P = 6.54 Hz, P–CH2), 3.52 (2H, s, N–CH2); 13C-NMR
(100.56 MHz, CDCl3) δ [ppm]: 145.8, 143.7, 136.1, 133.2,
132.3, 131.4, 131.4, 130.5, 129.8, 124.7, 124.1, 58.7. MS (M+•;
m/z): 418. IR (KBR) (vmax cmꢀ1): 2930 and 2853 (C-H), 1542
(N¼O), 1626 (C¼N), 1441 (C–N), 1384, 1231 (P¼O), 1020,
971 (P–O), 732 (P–C). Anal. Calcd. for C22H19N4O3P: C, 63.16;
H, 4.58, N, 13.39. Found: C, 63.03; H, 4.49; N, 13.30.
4-((4-((Diphenylphosphoryl)methyl)-1H-1,2,3-triazol-1-yl)
methyl)benzonitrile (6e).
Yellow solid, mp: 169–171°C.
31P-NMR (CDCl3) δ [ppm]: 24.39; 1H-NMR (400 MHz,
CDCl3) δ [ppm]: 7.92–6.88 (14H, m, Ar–H), 8.27 (1H, s,
2
N–CH¼), 5.57 (2H, d, JH-P = 6.54 Hz, P–CH2), 3.49 (2H, s,
N–CH2); 13C-NMR (100.56 MHz, CDCl3) δ [ppm]: 141.3, 136.4,
133.7, 133.2, 132.4, 131.3, 131.3, 130.7, 130.1, 124.1, 110.8,
119.8, 58.7. MS (M+•; m/z): 398. IR (KBR) (vmax cmꢀ1): 2936
and 2852 (C–H), 2230 (C≡N), 1624 (C¼N), 1445 (C–N), 1383,
1232 (P¼O), 1024, 975 (P–O), 733 (P–C). Anal. Calcd. for
C23H19N4OP: C, 69.34; H, 4.81, N, 14.06. Found: C, 69.25; H,
4.74; N, 13.92.
Microwave synthesis of 1-(substituted)-1H-1,2,3-triazol-4-yl)
methyl)diphenylphosphine oxides (6b–o).
As described in the
model reaction, 4 (0.5 mmol) and 5b–o (0.5 mmol), DMSO (5 mL),
NaN3 (42 mg, 0.65 mmol) in water (5 mL) and 0.5 mol% CuBr
(PPh3)3, (2.3 mg) were mixed thoroughly in a two-necked round-
bottom flask and exposed to MWI at 280 W with 80–120°C in
ambient pressure (Scheme 2). The reaction was completed (TLC) in
10–14 min. The compounds were purified as per the procedure
described in the model reaction. All the newly synthesized titled
((1-(2-Hydroxy-5-nitrobenzyl)-1H-1,2,3-triazol-4-yl)methyl)
diphenylphosphine oxide (6f). Yellow solid, mp: 174–176°C.
1
31P-NMR (CDCl3) δ [ppm]: 22.98, H-NMR (400 MHz, CDCl3)
1
compounds (6b–r) were characterized by IR, H-NMR, 13C-NMR,
δ [ppm]: 10.87 (1H, s, Ar–OH), 7.88–7.18 (13H, m, Ar–H), 8.25
2
31P-NMR, mass spectral, and elemental analysis.
(1H, s, N–CH¼), 5.56 (2H, d, JH-P = 6.54 Hz, P–CH2), 3.56
Physical and spectral characterization of the titled
compounds (6a–o). ((1-Benzyl-1H-1,2,3-triazol-4-yl)methyl)
diphenylphosphine oxide (6a). Yellow solid, mp: 166–168°C.
(2H, s, N–CH2); 13C-NMR (100.56 MHz, CDCl3) δ [ppm]:
163.7, 141.5, 136.3, 133.5, 132.4, 131.9, 131.7, 130.6, 129.8,
128.4, 126.3, 124.6, 116.5, 49.8. MS (M+•; m/z): 434. IR (KBR)
(vmax cmꢀ1): 3420 (O–H), 2932 and 2853 (C–H), 1623 (C¼N),
1548 (N¼O), 1446 (C–N), 1380, 1234 (P¼O), 1020, 976 (P–O),
730 (P–C). Anal. Calcd. for C22H19N4O4P: C, 60.83; H, 4.41, N,
12.90. Found: C, 60.74; H, 4.32; N, 12.84.
1
31P-NMR (CDCl3) δ [ppm]: 23.82. H-NMR (400 MHz, CDCl3)
δ [ppm]: 7.68–6.88 (15H, m, Ar–H), 8.21 (1H, s, N–CH¼), 5.48
2
(2H, d, JH-P = 6.54 Hz, P–CH2), 3.42 (2H, s, N–CH2); 13C-
NMR (100.56 MHz, CDCl3) δ [ppm]: 136.2, 135.3, 133.3,
131.2, 130.3, 129.5, 129.1, 127.9, 126.3, 123.4, 59.3, 39.6. MS
(M+•; m/z): 373. IR (KBR), (vmax cmꢀ1): 2932 and 2854 (C–H),
1621 (C¼N), 1443 (C–N), 1381, 1229 (P¼O), 1021, 975 (P–O),
735 (P–C). Anal. Calcd. for C22H20N3OP: C, 70.77; H, 5.40, N,
11.25. Found: C, 70.61; H, 5.32; N, 11.17.
((1-(6-Methylpyridin-2-yl)-1H-1,2,3-triazol-4-yl)methyl)
diphenylphosphine oxide (6g). Brown solid, mp: 168–170°C.
31P-NMR (CDCl3) δ [ppm]: 23.63; 1H-NMR (400 MHz, CDCl3)
δ [ppm]: 7.80–7.23 (13H, m, Ar–H), 8.24 (1H, s, N–CH¼), 5.54
2
(2H, d, JH-P = 6.54 Hz, P–CH2), 1.68 (3H, s, Ar–CH3); 13C-
((1-(4-Methylbenzyl)-1H-1,2,3-triazol-4-yl)methyl)
diphenylphosphine oxide (6b). Yellow solid, mp: 167–169°C.
NMR (100.56 MHz, CDCl3) δ [ppm]: 154.2, 141.3, 136.5,
133.5, 132.4, 131.5, 131.6, 130.6, 129.9, 125.1, 124.2, 120.7,
25.3. MS (M+•; m/z): 374. IR (KBR) (vmax cmꢀ1): 2935 and
2855 (C–H), 1625 (C¼N), 1447 (C–N), 1384, 1230 (P¼O),
1023, 977 (P–O), 733 (P–C). Anal. Calcd. for C21H19N4OP: C,
67.37; H, 5.12, N, 14.97. Found: C, 67.30; H, 5.03; N, 14.89.
((1-(2-Methylpyridin-3-yl)-1H-1,2,3-triazol-4-yl)methyl)
diphenylphosphine oxide (6h). Brown solid, mp: 161–163°C.
31P-NMR (CDCl3) δ [ppm]: 23.29; 1H-NMR (400 MHz, CDCl3)
δ [ppm]: 7.88–7.25 (13H, m, Ar–H), 8.20 (1H, s, N–CH¼), 5.50
1
31P-NMR (CDCl3) δ [ppm]: 23.90; H-NMR (400 MHz, CDCl3)
δ [ppm]: 7.46–6.96 (14H, m, Ar–H), 8.27 (1H, s, N–CH¼), 5.50
(2H, d, 2JH-P =6.54 Hz, P–CH2), 3.41 (2H, s, N–CH2), 1.58 (3H, s,
Ar–CH3); 13C-NMR (100.56 MHz, CDCl3) δ [ppm]: 136.1, 135.8,
134.2, 132.8, 131.3, 130.6, 129.4, 129.2, 127.7, 123.7, 59.5, 39.4,
23.5. MS (M+•; m/z): 387. IR (KBR) (vmax cmꢀ1): 2933 and 2854
(C–H), 1619 (C¼N), 1444 (C–N), 1380, 1228 (P¼O), 1024, 974
(P–O), 734 (P–C). Anal. Calcd. for C23H22N3OP: C, 71.31; H,
5.72, N, 10.85. Found: C, 71.22; H, 5.65; N, 10.77.
2
(2H, d, JH-P = 6.54 Hz, P–CH2), 1.66 (3H, s, Ar–CH3);
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Microwave-assisted Click Generation of 1,2,3-Triazol Containing
Diphenylphosphine Oxides
November 2015
1881
13C-NMR (100.56 MHz, CDCl3) δ [ppm]: 149.8, 142.8, 139.1,
136.7, 133.5, 132.5, 131.9, 131.5, 130.9, 130.3, 124.1, 121.6,
21.5. MS (M+•; m/z): 374. IR (KBR) (vmax cmꢀ1): 2932 and
2853 (C–H), 1634 (C¼N), 1443 (C–N), 1381, 1233 (P¼O),
1020, 976 (P–O), 735 (P–C). Anal. Calcd. for C21H19N4OP: C,
67.37; H, 5.12, N, 14.97. Found: C, 67.29; H, 5.04; N, 14.88.
((1-(3-Nitropyridin-2-yl)-1H-1,2,3-triazol-4-yl)methyl)
diphenylphosphine oxide (6i). Yellow solid, mp: 166–168°C.
(C¼O) 1644 (C¼N), 1436 (C–N), 1228 (P¼O), 932 (P–O), 739
(P–C). Anal. Calcd. for C19H18N5O3P: C, 57.72; H, 4.59, N,
17.71. Found: C, 57.64 H, 4.50; N, 17.64.
((1-(Pent-4-en-1-yl)-1H-1,2,3-triazol-4-yl)methyl)
diphenylphosphine oxide (6n).
Pale yellow solid, mp: 147–
149°C. 31P-NMR (CDCl3) δ [ppm]: δ 24.13; 1H-NMR (400 MHz,
CDCl3) δ [ppm]: 7.46–7.18 (10H, m, Ar–H), 8.12 (1H, s,
2
N–CH¼), 6.13 (1H, m, C–CH¼), 5.45 (2H, d, JH-P = 6.54 Hz,
1
31P-NMR (CDCl3) δ [ppm]: 23.67; H-NMR (400 MHz, CDCl3)
P–CH2), 5.35–5.27 (2H, m, ¼CH2), 2.63–2.51 (2H, t, N–CH2),
1.50–1.44 (4H, m, –(CH2–)2); 13C-NMR (100.56 MHz, CDCl3) δ
[ppm]: 138.1, 136.4, 133.7, 132.5, 131.1, 131.1, 130.3, 124.1,
118.2, 54.2, 33.5, 27.2; MS (M+•; m/z): 351. IR IR (KBR)
(vmax cmꢀ1): 2931 and 2853 (C–H), 1635 (C¼N), 1441 (C–N),
1382, 1228 (P¼O), 1631 (C¼C), 1022, 974 (P–O), 733 (P–C).
Anal. Calcd. for C20H22N3OP: C, 68.36; H, 6.31, N, 11.96.
Found: C, 68.27; H, 6.24; N, 11.88.
δ [ppm]: 7.98–7.28 (13H, m, Ar–H), 8.36 (1H, s, N–CH¼), 5.53
2
(2H, d, JH-P = 6.54 Hz, P–CH2); 13C-NMR (100.56 MHz,
CDCl3) δ [ppm]: 155.4, 150.2, 144.9 136.0, 133.6, 133.2, 132.3,
131.7, 131.3, 130.3, 125.6, 124.4. MS (M+•; m/z): 405. IR
(KBR) (vmax cmꢀ1): 2932 and 2853 (C–H), 1630 (C¼N), 1547
(N¼O), 1443 (C–N), 1381, 1228 (P¼O), 1021, 971 (P–O), 732
(P–C). Anal. Calcd. for C20H16N5O3P: C, 59.26; H, 3.98, N,
17.28. Found: C, 59.19; H, 3.89; N, 17.20.
((1-Pentyl-1H-1,2,3-triazol-4-yl)methyl)diphenylphosphine
2-(4-((Diphenylphosphoryl)methyl)-1H-1,2,3-triazol-1-yl)
oxide (6o).
Pale yellow solid, mp: 142–144°C. 31P-NMR
nicotinonitrile (6j). Brown solid, mp: 171–173°C. 31P-NMR
(CDCl3) δ [ppm]: δ 24.33; 1H-NMR (400 MHz, CDCl3) δ [ppm]:
7.41–7.16 (10H, m, Ar–H), 8.22 (1H, s, N–CH¼), 5.42 (2H, d,
1
(CDCl3) δ [ppm]: 23.11; H-NMR (400 MHz, CDCl3) δ [ppm]:
3
7.98–7.28 (13H, m, Ar–H), 8.37 (1H, s, N–CH¼), 5.55 (2H, d,
2JH-P = 6.54 Hz, P–CH2); 13C-NMR (100.56 MHz, CDCl3) δ
[ppm]: 158.2, 153.6, 141.3, 135.9, 133.9, 133.1, 132.3, 131.7,
131.1, 130.5, 124.2, 117.8, 108.2. MS (M+•; m/z): 385. IR
(KBR) (vmax cmꢀ1): 2937 and 2856 (C–H), 2235 (C≡N), 1629
(C¼N), 1448 (C–N), 1385, 1235 (P¼O), 1020, 973 (P–O), 737
(P–C). Anal. Calcd. for C21H16N5OP: C, 65.45; H, 4.18, N,
18.17. Found: C, 65.37; H, 4.07; N, 18.09.
2JH-P = 6.54 Hz, P–CH2), 2.58 (2H, t, JH-H = 2.20 Hz, N–CH2),
3
1.50–1.41 (4H, m, –(CH2–)3), 1.79 (2H, t, JH-H = 6.51 Hz,
CH3); 13C-NMR (100.56 MHz, CDCl3) δ [ppm]: 135.9, 133.3,
132.3, 131.1, 131.1, 130.4, 124.9, 53.2, 30.8, 29.8, 23.5, 15.3.
MS (M+•; m/z): 353. IR (KBR) (vmax cmꢀ1): 2933 and 2854 (C–
H), 1637 (C¼N), 1444 (C–N), 1383, 1230 (P¼O), 1024, 972
(P–O), 735 (P–C). Anal. Calcd. for C20H24N3OP: C, 67.97; H,
6.85, N, 11.89. Found: C, 67.90; H, 6.76; N, 11.80.
((1-(4-Methylquinolin-2-yl)-1H-1,2,3-triazol-4-yl)methyl)
diphenylphosphine oxide (6k). Brown solid, mp: 176–178°C.
31P-NMR (CDCl3) δ [ppm]: 24.36; H-NMR (CDCl3) δ [ppm]:
1
Acknowledgements. We thank Prof. C. Devendranath Reddy,
Department of Chemistry, Sri Venkateswara University, Tirupati,
for his helpful discussions and Council of Scientific and Industrial
Research (CSIR), New Delhi, India for providing financial
assistance (S. No.: 02(0137)/13/EMR-II, dated 12-04-2013).
7.83–7.28 (15H, m, Ar–H), 8.26 (1H, s, N–CH¼), 5.55 (2H, d,
2JH-P = 6.54 Hz, P–CH2), 1.96 (3H, s, Ar–CH3); 13C-NMR
(100.56 MHz, CDCl3) δ [ppm]: 147.9, 146.8, 146.1, 135.5,
133.2, 132.3, 131.9, 131.5, 130.9, 130.4, 130.1, 127.1, 125.9,
125.5, 124.3, 113.5, 21.0. MS (M+•; m/z): 424. IR (KBR)
(vmax cmꢀ1): 2937 and 2855 (C–H), 1628 (C¼N), 1449 (C–N),
1378, 1236 (P¼O), 1027, 975 (P–O), 738 (P–C). Anal. Calcd.
for C25H21N4OP: C, 70.75; H, 4.99, N, 13.20. Found: C, 70.66;
H, 4.90; N, 13.12.
REFERENCES AND NOTES
[1] Sugawara, A.; Sunazuka, T.; Hirose, T.; Nagai, K.;
Yamaguchi, Y.; Hanaki, H.; Sharpless, K. B.; Omura, S. Bioorg Med
Chem Lett 2007, 17, 6340.
[2] Tron, G. C.; Pirali, T.; Billington, R. A.; Canonico, P. L.;
Sorba, G.; Genazzani, A. A. Med Res Rev 2008, 28, 278.
[3] Wacharasindhu, S.; Bardhan, S.; Wan, Z. K.; Tabei, K.;
Mansour, T. S. J Am Chem Soc 2009, 131, 4174.
[4] Hanselmann, R.; Job, G. E.; Johnson, G.; Lou, R. L.;
Martynow, J. G.; Reeve, M. M. Org Process Res Dev 2010, 14, 152.
[5] Mamidyala, S. K.; Finn, M. G. Chem Soc Rev 2010, 39, 1252.
[6] Boren, B. C.; Narayan, S.; Rasmussen, L. K.; Zhang, L.;
Zhao, H.; Lin, Z.; Jia, G.; Fokin, V. J Am Chem Soc 2008, 130, 8923.
[7] Steven, L.; Silvia, D.-G. J Org Chem 2011, 76, 2367.
[8] Huisgen, R. Helv Chim Acta 1967, 50, 2421.
((1-(8-Hydroxyquinolin-5-yl)-1H-1,2,3-triazol-4-yl)methyl)
diphenylphosphine oxide (6l). Brown solid, mp: 174–176°C.
31P-NMR (CDCl3) δ [ppm]: δ 23.93; 1H-NMR (400 MHz,
CDCl3) δ [ppm]: 7.89–7.18 (15H, m, Ar–H), 8.21 (1H, s,
2
N–CH¼), 5.51 (2H, d, JH-P = 6.54 Hz, P–CH2), 10.26 (1H, s,
Ar–OH); 13C-NMR (100.56 MHz, CDCl3) δ [ppm]: 156.5,
152.1, 139.6, 135.8, 133.8, 133.3, 132.5, 131.6, 131.2, 130.1,
127.6, 127.1, 124.5, 123.1, 118.9, 114.8. MS (M+•; m/z): 426.
IR (KBR), (vmax cmꢀ1): 3430 (OH), 2936 and 2859 (C–H), 1645
(C¼N), 1449 (C–N), 1385, 1226 (P¼O), 1021, 972 (P–O), 730
(P–C). Anal. Calcd. for C24H19N4O2P: C, 67.60; H, 4.49, N,
13.14. Found: C, 67.52; H, 4.41; N, 13.08.
5-(4-((Diphenylphosphoryl)methyl)-1H-1,2,3-triazol-1-yl)
dihydropyrimidine-2,4(1H,3H)-dione (6m). Brown solid, mp:
148–150°C. 31P-NMR (CDCl3) δ [ppm]: 24.59; 1H-NMR
(400 MHz, CDCl3) δ [ppm]: 9.92 (1H, s, CO–NH–CO), 8.22
(1H, s, C–NH–CO), 8.20 (1H, s, N–CH¼), 7.48–7.18 (10H, m,
N–CH), 2.70–2.55 (2H, m, N–CH2), 13C-NMR (100.56 MHz,
CDCl3) δ [ppm]: 178.5, 165.1, 135.7, 133.7, 132.6, 131.2,
131.5, 130.9, 124.2, 77.3, 42.3. MS (M+•; m/z): 395. IR (KBR)
(vmax cmꢀ1): 3341–3354 (NH), 2982 and 2863 (C–H), 1695–1710
[9] Rostovtsev, V. V.; Green, L. G.; Fokin, V. V.; Sharpless, K. B.
Angew Chem Int Ed 2002, 41, 2596.
[10] Angell, Y. L.; Burgess, K. Chem Soc Rev 2007, 36, 1674.
[11] Fournier, D.; Hoogenboom, R.; Schubert, U. S. Chem Soc Rev
2007, 36, 1369.
[12] Moses, J. E.; Moorhouse, A. D. Chem Soc Rev 2007; 36; 1249.
[13] Radha Rani, C.; Ira, B.; Chandra Sekhar Reddy, G.; Syama
Sundar, Ch.; Suresh Reddy, C. Arch Pharm Chem Life Sci 2013, 346, 667.
[14] Chandra Sekhar Reddy, G.; Veeranarayana Reddy, M.;
Radha Rani, C.; Bakthavatchala Reddy, N.; Uma Maheswara Rao, K.;
Nayak, S. K.; Suresh Reddy, C. Heteroatom Chem 2012, 23, 247.
2
Ar–H), 5.50 (2H, d, JH-P = 6.54 Hz, P–CH2), 3.44–3.37 (1H, m,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

1882
R. R. Chinthaparthi, C. S. R. Gangireddy, M. K. R. Kandula, S. K. Balam, and S. R. Cirandur
Vol 52
[15] Veeranarayana Reddy, M.; Balakrishna, A.; Anil Kumar, M.;
[21] Veeranarayana Reddy, M.; Chandra Sekhar Reddy, G.; Syama
Chandra Sekhar Reddy, G.; Uma Ravi Sankar, A.; Suresh Reddy, C.;
Murali Krishna, T. Chem Pharm Bull 2009, 57, 1391.
[16] Han, Y.; Belley, M.; Bayly, C. I.; Colucci, J.; Dufresne, C.;
Giroux, A.; Lau, C. K.; Leblanc, Y.; McKay, D.; Therien, M.; Wilson,
M.-C.; Skorey, K.; Chan, C. -C.; Scapin, G.; Kennedy, B. P. Bioorg
Med Chem Lett 2008, 18, 3200.
Sundar, Ch.; Suresh Kumar, K.; Ananda Kumar, K.; Suresh Reddy, C.
Green Chem Lett Rev 2012, 5, 475.
[22] Dömling, A. Chem Rev 2006, 106, 17.
[23] Caddick, S.; Fitzmaurice, R. Tetrahedron 2009, 65, 3325.
[24] Cakmakcl, E.; Mülazim, Y.; Vezir Kahraman, M.; Kayaman
Apohan, N. React Funct Polym 2011, 71, 36.
[17] Artyushin, O. I.; Vorob’eva, D. V.; Vasil’eva, T. P.; Osipov, S. N.;
Röschenthaler, G. V.; Odinets, I. L. Heteroatom Chem 2008, 19, 293.
[18] Detz, R. J.; Heras, S. A.; de Gelder, R.; van Leeuwen,
P. W. N. M.; Hiemstra, H.; Reek, J. N. H.; van Maarseveen, J. H.
Org Lett 2006, 8, 3227.
[25] Bagdasaryana, G. B.; Pogosyana, P. S.; Panosyanb, G. A.;
Indzhikyan, M. G.; Russian J Gen Chem 2008, 78, 1177.
[26] Hein, J. E.; Fokin, V. V. Chem Soc Rev 2010, 39, 1302.
[27] Valentin, O. R.; Valery, V. F.; Finn, M. G. Angew Chem Int
Ed 2005, 44, 2210.
[19] Radha Rani, C.; Chandra Sekhar Reddy, G.; Veeranarayana
Reddy, M.; Mohan, G.; Nagaraju, C.; Suresh Reddy, C. Tetrahedron Lett
2013, 54, 6071.
[20] Chandra Sekhar Reddy, G.; Veeranarayana Reddy, M.;
Bakthavatchala Reddy, N.; Suresh Reddy, C. Phosphorus, Sulfur and
Silicon 2011, 186, 74.
[28] Zhang, L.; Chen, X.; Xue, P.; Sun, H. H. Y.; Williams, I. D.;
Sharpless, K. B.; Fokin, V. V.; Jia, G. J Am Chem Soc 2005, 127, 15998.
[29] Appukkuttan, P.; Dehaen, W.; Fokin, V. V.; Vander Evcken, E.
Org Lett 2004, 6, 4223.
[30] Bagdasaryana, G. B.; Pogosyana, P. S.; Panosyanb, G. A.;
Indzhikyan, M. G. Russian J Gen Chem 2008, 78, 1177.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet