Synthesis, structural and spectroscopic characterization of thiophosphorodiamidates and effect of ZnCl2 on the hydrolysis of the P-N bond

Article abstract of DOI:10.1016/j.poly.2012.07.033

New N,N′-dibenzylthiophosphorodiamidate derivatives were synthesized from the corresponding thiophosphorodichloridate intermediates and benzylamine. Several compounds with formula 2-MeC₆H₄OP(S)(NHBn) ₂ (6), 2-FC₆

Full text of DOI:10.1016/j.poly.2012.07.033

Polyhedron 52 (2013) 831–836
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Polyhedron
journal homepage: www.elsevier.com/locate/poly
Synthesis, structural and spectroscopic characterization of
thiophosphorodiamidates and effect of ZnCl2 on the hydrolysis of the P–N bond
⇑
Payal Malik, Debashis Chakraborty
Department of Chemistry, Indian Institute of Technology Madras, Chennai 600 036, Tamil Nadu, India
a r t i c l e i n f o
a b s t r a c t
New N,N0-dibenzylthiophosphorodiamidate derivatives were synthesized from the corresponding
thiophosphorodichloridate intermediates and benzylamine. Several compounds with formula
2-MeC6H4OP(S)(NHBn)2 (6), 2-FC6H4OP(S)(NHBn)2 (7), 2-ClC6H4OP(S)(NHBn)2 (8), 4-MeC6H4OP(S)(NHBn)2
(9) and 4-t-BuC6H4OP(S)(NHBn)2 (10) were synthesized and characterized by 1H, 13C, 31P NMR, IR, mass
spectroscopy and elemental analysis. The single crystal X-ray diffraction studies of 6 and 7 have been
described. ZnCl2 assisted P–N bond hydrolysis of thiophosphorodiamidates was investigated.
Ó 2012 Elsevier Ltd. All rights reserved.
Article history:
Available online 20 July 2012
This paper is dedicated to Prof. Alfred
Werner to commemorate the 100th
anniversary of the award of Nobel Prize to
him.
Keywords:
Thiophosphorodiamidate
N,N0-dibenzylthiophosphorodiamidate
Thiophosphorodichloridate
Zinc chloride
Hydrolysis
Single crystal X-ray diffraction
1. Introduction
organophosphorus esters thioesters are considered as eco-friendly
agrochemicals. The occurrence of phosphates in plants implied an
In the past three decades, organophosphorus chemistry has
blossomed at an exceeding pace due to their wide range of applica-
tions in agriculture [1], biology [2,3], pharmaceuticals [4–10] and
chemical synthesis [11–17]. Phosphines, phosphites, phosphinites
and amidophosphinites are frequently used in homogeneous catal-
ysis [18–20]. As a recent development, phosphoroamidates chem-
istry received significant attention because of their biological
activity [21–27] and coordination properties [28–32]. The presence
of the P–N bond and its susceptibility to cleave in aqueous acidic/
basic solutions made these phosphoramidates an interesting class
of compounds [33], since the phosphate esters and their structural
analogues represent a major class of biomolecules that plays cen-
tral roles in genetic transmission and metabolism. This concept
has been used for developing the several prodrugs [34] such as
1,2-benzisoxazole phosphorodiamidates [35], naphthoquinone
and benzimidazolequinone phosphorodiamidates [36]. The new
methods for the intracellular delivery of nucleotides have resulted
in the synthesis of several biologically active nucleoside phospho-
ramidates that act as prodrugs for the known thymidylate synthase
inhibitor, 5-fluoro-20-deoxyuridine 50-monophosphate [37]. Orga-
nophosphorus esters and thioesters are widely used in the agricul-
ture industry as well as in organic synthesis [38–41]. Among the
important role of phosphates and in the processes of life [42]. In
fact, the role of phosphates in biochemistry was foreshadowed
by the use of phosphates as fertilizers. Owing to their biological
and physical properties, a number of phosphorothioates have been
introduced as potential chemotherapeutic agent in the recent years
[43–48]. Regardless of their biological activities and synthetic util-
ity, the synthesis of phosphorothioates did not receive much
attention.
In our previous work, we have reported the ZnCl2 assisted P–N
bond hydrolysis of phosphorodiamidates [49]. The results evoked
us to investigate the effect of ZnCl2 on the P–N bond hydrolysis
of thiophosphorodiamidates. Herein, we have synthesized and
characterized various thiophosphorodiamidate compounds and
compared their reactivity with the respective phosphorodiamidate
derivatives.
2. Experimental
2.1. General methods
The reactions for the synthesis of thiophosphorodichloridates
and thiophosphorodiamidates were performed under a dry argon
atmosphere using standard Schlenk techniques with the rigorous
exclusion of moisture and air. Toluene was dried by heating under
reflux over sodium and benzophenone and distilled fresh prior to
⇑
Corresponding author. Tel.: +91 44 22574223; fax: +91 44 22574202.
E-mail address: dchakraborty@iitm.ac.in (D. Chakraborty).
0277-5387/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.poly.2012.07.033

832
P. Malik, D. Chakraborty / Polyhedron 52 (2013) 831–836
use. All the phenols used in this study along with thiophosphoryl
chloride and zinc chloride were purchased from Aldrich and used
without subsequent purification. Toluene, hexane, ethyl acetate,
methylene chloride, chloroform and tetrahydrofuran were pur-
chased from Ranchem India. CDCl3 used for NMR spectral measure-
ments was purchased from Aldrich and was dried by stirring over
CaH2 and distilled prior to use.
122.67; 31P NMR (161 MHz, CDCl3, ppm): d 48.14 (s); GC–MS:
260.57 (M+H)+; Anal. Calc. for C6H4Cl3OPS: C, 27.56; H, 1.54. Found:
C, 28.23; H, 2.01%.
2.3.3. 4-MeC6H4OP(S)Cl2 (4)
The compound 4 was synthesized from 4-MeC6H4OH (1.0 g,
9.2 mmol), PSCl3 (6.2 g, 36.8 mmol) and tetra-butylammonium
bromide (73 mg, 0.2 mmol); Yield = 1.6 g (76%); IR (neat, cmꢁ1):
2957 (C–H), 667 (P@S), 523 (P–Cl); 1H NMR (400 MHz, CDCl3,
ppm): d 7.20–7.18 (m, 4H, Ar), 2.36 (s, 3H, ArMe); 13C NMR
(100 MHz, CDCl3, ppm): d 148.83, 137.15, 130.71, 121.31, 18.86;
31P NMR (161 MHz, CDCl3, ppm): d 48.04 (s); GC–MS: 240.83; Anal.
Calc. for C7H7Cl2OPS: C, 34.88; H, 2.93. Found: C, 34.97; H, 2.57%.
2.2. Instrumentation
1H and 13C NMR spectra were recorded with a Bruker Avance
400 instrument. Chemical shifts for 1H and 13C NMR spectra were
referenced to residual solvent resonances and are reported as parts
per million relative to SiMe4. 31P NMR spectra were recorded rela-
tive to 85% H3PO4 as an external standard. Mass spectra of the sam-
ples were recorded using a Micromass QToF instrument, low
resolution Electro-Spray Ionization (ESI) mass spectrometer using
methanol solvent. GC–MS were recorded using Jeol JMS GC-Mate
II instrument. Infrared spectra were recorded using a Nicolet
6700 FTIR instrument. Elemental analyses were done with a Perkin
Elmer Series 11 analyzer.
2.3.4. 4-t-BuC6H4OP(S)Cl2 (5)
The compound 5 was synthesized from 4-t-BuC6H4OH (1.0 g,
6.8 mmol), PSCl3 (4.6 g, 27.2 mmol) and tetra-butylammonium
bromide (54 mg, 0.17 mmol). Yield = 1.5 g (81%); IR (neat, cmꢁ1):
2997 (C–H), 690 (P@S), 520 (P–Cl); 1H NMR (400 MHz, CDCl3,
ppm): d 7.44–7.41 (d, 2H, Ar), 7.23–7.20 (d, 2H, Ar), 1.33 (s, 9H,
Ar–CMe3); 13C NMR (100 MHz, CDCl3, ppm): d 150.13, 148.26,
126.98, 120.83, 34.72, 31.47; 31P NMR (161 MHz, CDCl3, ppm): d
48.54 (s); GC–MS: 280.40; Anal. Calc. for C10H13Cl2OPS: C, 42.42;
H, 4.63. Found: C, 42.17; H, 4.98%.
2.3. Synthesis of thiophosphorodichloridates (1–5)
The required phenol (1 mmol) was added to a stirred solution of
aqueous NaOH (25%, 15 mL) at 0 °C. This solution was added drop
wise to the thiophosphoryl chloride (4 mmol) solution dissolved in
dichloromethane (10 mL) along with tetrabutylammonium bro-
mide (0.025 mmol) at 0 °C. The reaction was allowed to warm-up
to room temperature. The reaction was monitored using TLC (5%
EtOAc in hexane) against the required phenol. The time required
for completion of the reaction was found to be 5 h for 1, 4 and 5
and 8 h for 2 and 3. The reaction mixture was quenched with water
(7 mL) and extracted with CH2Cl2 (3 ꢀ 10 mL). The organic layer
was separated and dried over MgSO4 (anhyd.) and was evaporated
to obtain the crude product. The crude product was purified by dis-
tillation under reduced pressure to yield the thiophosphorodichlo-
ridates as colorless viscous liquids.
2.4. Synthesis of N,N0-dibenzylthiophosphorodiamidates (6–10)
An arylthiophosphorodichloridate (1 mmol) and benzylamine
(4 mmol) in a stoichiometric ratio 1:4 were stirred for 12 h at
80 °C in toluene (10 mL) to produce the corresponding N,N0-diben-
zylthiophosphorodiamidate. The reaction was monitored by TLC
(70% EtOAc in hexane) against the respective arylthiophosphorod-
ichloridate. The reaction was quenched with water (10 mL) and ex-
tracted with CH2Cl2 (3 ꢀ 10 mL) and the organic layer was
separated and dried over MgSO4 (anhyd.). Removal of the volatiles
gave the crude product which was subsequently purified by col-
umn chromatography (70% of CHCl3 in hexane as eluent) and ob-
tained as white solids after removal of volatiles.
The compound 1 was synthesized from 2-MeC6H4OH (1.0 g,
9.2 mmol), PSCl3 (6.2 g, 36.8 mmol) and tetra-butylammonium
bromide (73 mg, 0.2 mmol); Yield = 1.8 g (80%); IR (neat, cmꢁ1):
3069 (C–H), 693 (P@S), 560 (P–Cl); 1H NMR (400 MHz, CDCl3,
ppm): d 7.37–7.28 (m, 2H, Ar), 7.25–7.20 (m, 2H, Ar), 2.37 (s, 3H,
2.4.1. 2-MeC6H4OP(S)(NHBn)2 (6)
The compound 6 was synthesized from 1 (0.5 g, 2 mmol) and
BnNH2 (0.86 g, 8 mmol); Yield = 0.54 g (73%); M.p. = 61 °C; IR
(neat, cmꢁ1): 3376 (N–H), 3188 (C–H), 695 (P@S); 1H NMR
(400 MHz, CDCl3, ppm): d 7.39–7.29 (m, 11H, Ar), 7.25–7.18 (m,
2H, Ar), 7.11–7.13, (m, 1H, Ar), 4.35–4.23 (m, 4H, CH2Bn), 3.12
(br, 2H, NH), 2.34 (s, 3H, ArMe). 13C NMR (100 MHz, CDCl3, ppm):
d 150.03, 139.10, 131.45, 130.07, 128.79, 127.63, 126.90, 124.76,
120.45, 45.97, 17.10; 31P NMR (161 MHz, CDCl3, ppm): d 62.92;
ArMe); 13C NMR (100 MHz, CDCl3, ppm):
d
150.04, 132.08,
130.41, 127.32, 126.95, 120.78, 17.06; 31P NMR (161 MHz, CDCl3,
ppm):
48.04 (s); GC–MS: 240.69 (M+H)+; Anal. Calc. for
d
C7H7Cl2OPS: C, 34.88; H, 2.93. Found: C, 33.91; H, 2.99%.
2.3.1. 2-FC6H4OP(S)Cl2 (2)
HRMS (ESI)
383.1342.
C
21H23N2OSP (M+H)+: Calc., 383.1301. Found:
The compound 2 was synthesized from 2-FC6H4OH (1.0 g,
8.9 mmol), PSCl3 (6.0 g, 35.6 mmol) and tetra-butylammonium
bromide (71 mg, 0. 22 mmol); Yield = 1.6 g (75%); IR (neat,
cmꢁ1): 3012 (C–H), 691 (P@S), 537,(P–Cl); 1H NMR (400 MHz,
CDCl3, ppm): d 7.43–7.30 (m, 1H, Ar), 7.30–7.25 (m, 2H, Ar),
7.22–7.20 (m, 1H, Ar); 13C NMR (100 MHz, CDCl3, ppm): d 152.54,
137.83, 128.25, 124.87, 123.58, 117.60; 31P NMR (161 MHz, CDCl3,
2.4.2. 2-FC6H4OP(S)(NHBn)2 (7)
The compound 7 was synthesized from 2 (0.5 g, 2 mmol) and
BnNH2 (0.86 g, 8 mmol). Yield = 0.55 g (70%); M.p. = 97 °C; IR (neat,
cmꢁ1): 3373 (N–H), 3033 (C–H), 689 (P@S); 1H NMR (400 MHz,
CDCl3, ppm): d 7.33–7.23 (m, 11H, Ar), 7.12–7.07 (m, 3H, Ar),
4.25–4.21 (m, 4H, CH2Bn), 3.41 (br, 2H, NH); 13C NMR (100 MHz,
CDCl3, ppm): d 153.31, 144.46, 139.13, 128.79, 127.79, 127.63,
125.86, 124.52, 124.25, 116.69, 45.99; 31P NMR (161 MHz, CDCl3,
ppm):
d
49.51 (s); GC–MS: 244.20 (M+H)+; Anal. Calc. for
C6H4Cl2FOPS: C, 29.41; H, 1.65. Found: C, 29.83; H, 1.17%.
2.3.2. 2-ClC6H4OP(S)Cl2 (3)
ppm): d
65.75; HRMS (ESI) C20H20FN2OSP (M+H)+: Calc.,
The compound 3 was synthesized from 2-ClC6H4OH (1.0 g,
7.8 mmol), PSCl3 (5.2 g, 31.2 mmol) and tetra-butylammonium
bromide (60 mg, 0.19 mmol); Yield = 1.4 g (72%); IR (neat, cmꢁ1):
3094 (C–H), 667 (P@S), 529 (P–Cl); 1H NMR (400 MHz, CDCl3,
ppm): d 7.56–7.49 (m, 2H, Ar), 7.38–7.28 (m, 2H, Ar); 13C NMR
(100 MHz, CDCl3, ppm): d 146.82, 131.23, 127.92, 127.89, 126.87,
387.1012. Found: 387.1100.
2.4.3. 2-ClC6H4OP(S)(NHBn)2 (8)
The compound 8 was synthesized from 3 (0.5 g, 2 mmol) and
BnNH2 (0.86 g, 8 mmol); Yield = 0.56 g (71%); M.p. = 70 °C; IR (neat,
cmꢁ1): 3368 (N–H), 3029 (C–H), 680 (P@S); 1H NMR (400 MHz,

P. Malik, D. Chakraborty / Polyhedron 52 (2013) 831–836
833
CDCl3, ppm): d 7.46–7.19 (m, 13H, Ar), 7.17–7.07 (m, 1H, Ar), 4.23–
4.20 (m, 4H, CH2Bn), 3.43 (br, 2H, NH). 13C NMR (100 MHz, CDCl3,
ppm): d 147.53, 139.11, 130.49, 128.71, 128.79, 127.78, 127.63,
125.74, 123.52, 46.04; 31P NMR (161 MHz, CDCl3, ppm): d 65.75;
HRMS (ESI)
403.0808.
(N–H), 1221 (P@S), 684 (P–N); 1H NMR (400 MHz, CDCl3, ppm): d
7.51–7.33 (m, 2H, Ar), 7.31–7.24 (m, 6H, Ar), 7.16–7.12 (m, 1H,
Ar), 5.04 (b, 4H, OH and NH2), 4.33–4.26 (m, 2H, CH2Ph),; 13C
NMR (100 MHz, CDCl3, ppm): d 148.27, 139.11, 130.50, 128.78,
127.79, 127.63, 126.27, 125.79, 123.10, 46.02; 31P NMR
(161 MHz, CDCl3, ppm): d 64.12; HRMS (ESI) C13H14ClNO3PS
(M+THF)+: Calc., 403.0711. Found: 403.0779.
C
20H20ClN2OSP (M+H)+: Calc., 403.8001. Found:
2.4.4. 4-MeC6H4OP(S)(NHBn)2 (9)
The compound 9 was synthesized from 4 (0.45 g, 2 mmol) and
BnNH2 (0.86 g, 8 mmol); Yield = 0.55 g (74%); M.p. = 65 °C. IR (neat,
cmꢁ1): 3377 (N–H), 3010 (C–H), 646 (P@S); 1H NMR (400 MHz,
CDCl3, ppm): d 7.26–7.17 (m, 10H, Ar), 7.04–7.00 (m, 4H, Ar),
4.16–4.11 (m, 4H, CH2Bn), 3.21 (br, 2H, NH), 2.24 (s, 3H, Ar–Me);
2.5.4. [4-MeC6H4OP(S)O(OH)][BnNH3] (14)
The compound 14 was synthesized from 9 (0.10 g, 0.27 mmol)
and ZnCl2 (37 mg). Yield = 0.061 g (73%); IR (neat, cmꢁ1): 3371
(N–H), 1229 (P@S), 692 (P–N); 1H NMR (400 MHz, CDCl3, ppm): d
7.26–7.19 (m, 5H, Ar), 7.04–6.92 (m, 4H, Ar), 4.81 04 (b, 4H, OH
and NH2), 4.20–4.17 (m, 2H, CH2Ph), 2.22 (s, 3H, Ar–Me); 13C
NMR (100 MHz, CDCl3, ppm): d 149.35, 138.15, 131.69, 129.98,
128.83, 127.88, 127.14, 125.47, 120.41, 46.02, 25.60; 31P NMR
(161 MHz, CDCl3, ppm): d 61.67; HRMS (ESI) for C14H18NO3SP
(M+THF)+: Calc., 367.1549. Found: 383.1813.
13C NMR (100 MHz, CDCl3, ppm):
d 148.75, 139.17, 134.55,
130.10, 128.77, 127.81, 127.60, 121.17, 115.24, 45.94, 20.91; 31P
NMR (161 MHz, CDCl3, ppm): d 65.37; HRMS (ESI) C21H23N2OSP
(M+H)+: Calc., 383.1317. Found: 383.1351.
2.4.5. 4-t-BuC6H4OP(S)(NHBn)2 (10)
The compound 10 was synthesized from 5 (0.53 g, 2 mmol) and
BnNH2 (0.86 g, 8 mmol); Yield = 0.62 g (75%); M.p. = 53 °C; IR
(neat, cmꢁ1): 3374 (N–H), 3031 (C–H), 686 (P@S); 1H NMR
(400 MHz, CDCl3, ppm): d 7.34–7.26 (m, 12H, Ar), 7.14–7.12 (m,
2H, Ar), 4.25–4.20 (m, 4H, CH2Bn), 2.91(br, 2H, NH), 1.32 (s, 9H,
Ar–CMe3); 13C NMR (100 MHz, CDCl3, ppm): d 148.54, 147.71,
139.11, 128.75, 127.80127.45, 127.72, 127.59, 126.48, 120.69,
45.89, 34.49, 31.55; 31P NMR (161 MHz, CDCl3, ppm): d 62.53;
HRMS (ESI) for C24H29N2OSP (M+H)+: Calc., 425.1721. Found:
425.1823.
2.5.5. [4-t-BuC6H4OP(S)O(OH)][BnNH3] (15)
The compound 15 was synthesized from 10 (0.10 g, 0.24 mmol)
and ZnCl2 (33 mg). Yield = 0.062 g (75%); IR (neat, cmꢁ1): 3386 (N–
H), 1212 (P@S), 687 (P–N); 1H NMR (400 MHz, CDCl3, ppm): d
7.23–7.15 (m, 7H, Ar), 7.03–7.00 (m, 2H, Ar), 4.71 (b, 4H, OH and
NH2) 4.14–4.09 (m, 2H, CH2Ph), 1.20 (s, 9H, Ar-CMe3); 13C NMR
(100 MHz, CDCl3, ppm): d 148.97, 139.15, 128.78, 127.82, 127.62,
126.50, 120.71, 45.19, 34.51, 31.57; 31P NMR (161 MHz, CDCl3,
ppm): d 60.51; HRMS (ESI) for C17H24NO3PS (M+THF)+: Calc.,
425.1708. Found: 425.1788.
2.5. Synthesis of thiophosphonate (11–15)
2.6. X-ray crystallography
To a stirred solution of N,N0-dibenzylthiophosphorodiamidate
in THF (10 mL), ZnCl2 was added in a stoichiometric ratio 1:1 and
the reaction mixture was subjected to reflux. The time required
for completion of the reaction was found to be 12 h for compounds
11, 14 and 15 and 20 h for 12 and 13. The solvent was removed un-
der reduced pressure and the reaction mixture was extracted with
toluene and subsequently filtered. Evaporation of the solvent
yielded the crude product. Crude product was purified by
crystallization.
Single crystals of compounds 6 and 7 suitable for structural
studies were obtained by crystallization from methanol at room
temperature over a period of one week. X-ray data collection was
performed with Bruker AXS (Kappa Apex 2) CCD diffractometer
equipped with graphite monochromated Mo K
radiation source. The data were collected with 100% completeness
for h up to 25°. and / scans were employed to collect the data.
The frame width for was set to 0.5° for data collection. The
a (k = 0.7107 Å)
x
x
frames were integrated and the data were reduced for Lorentz
and polarization corrections using SAINT-NT. The multi-scan absorp-
tion correction was applied to the data set. All structures were
solved using SIR-92 and refined using SHELXL-97 [50]. The crystal
data are summarized in Table 1. The non-hydrogen atoms were re-
fined with anisotropic displacement parameter. All the hydrogen
atoms could be located in the difference Fourier map. The hydro-
gen atoms bonded to carbon atoms were fixed at chemically mean-
ingful positions and were allowed to ride with the parent atom
during refinement.
2.5.1. [2-MeC6H4P(S)O(OH)][BnNH3] (11)
The compound 11 was synthesized from 6 (0.10 g, 0.26 mmol)
and ZnCl2 (37 mg); Yield = 0.052 g (66%); IR (neat, cmꢁ1): 3381
(N–H), 1223 (P@S), 690 (P–N); 1H NMR (400 MHz, CDCl3, ppm): d
7.34–7.16 (m, 5H, Ar), d 7.14–7.08 (m, 4H, Ar), 4.33–4.22 (m, 2H,
CH2Ph), 4.12 (b, 1H, OH), 1.90; 13C NMR (100 MHz, CDCl3, ppm):
d 148.30, 138.16, 131.62, 129.91, 128.76, 127.81, 127.71, 127.07,
125.40, 120.35, 45.95, 17.00; 31P NMR (161 MHz, CDCl3, ppm): d
61.07; HRMS (ESI) C14H18NO3PS (M+THF)+: Calc., 383.1237. Found:
383.1314.
3. Results and discussion
2.5.2. [2-FC6H4OP(S)O(OH)][BnNH3] (12)
The compound 12 was synthesized from 7 (0.10 g, 0.27 mmol)
and ZnCl2 (36 mg); Yield = 0.055 g (65%); IR (neat, cmꢁ1): 3302
(N–H), 1202 (P@S), 693 (P–N); 1H NMR (400 MHz, CDCl3, ppm): d
7.29–7.09 (m, 9H, Ar), 4.19 (m, 2H, CH2Ph), 3.91 (b, 1H, OH). 13C
NMR (100 MHz, CDCl3, ppm): d 152.47, 143.12, 139.22, 128.77,
127.78, 127.61, 125.90, 124.27, 123.43, 116.85, 45.26 15.64; 31P
3.1. Synthesis and characterization
The arylthiophosphodichloridates 1–5 were synthesized by the
literature procedure [51]. Phenols were treated with PSCl3 in the
presence of catalytic amount of TBAB (as phase transfer catalyst)
in CH2Cl2 at room temperature (Scheme 1). The arylthiophosphod-
ichloridates were isolated in good yields (70–80%) as colorless vis-
cous liquids after distillation under reduced pressure. These
compounds were characterized by various spectroscopic methods,
Out of these compounds the elemental analysis of compound 3 is
reported in the literature [51]. Our contribution is that we have
characterized all these compounds by 1H, 13C, 31P NMR and mass
NMR (161 MHz, CDCl3, ppm):
C
d
62.31; HRMS (ESI) for
13H14FNO3PS (M+THF)+: Calc., 387.1000. Found: 387.1071.
2.5.3. [2-ClC6H4OP(S)O(OH)][BnNH3] (13)
The compound 13 was synthesized from 8 (0.10 g, 0.25 mmol)
and ZnCl2 (35 mg). Yield = 0.051 g (62%); IR (neat, cmꢁ1): 3366

834
P. Malik, D. Chakraborty / Polyhedron 52 (2013) 831–836
Table 1
Crystal data 6 and 7.
6
7
Empirical formula
Formula weight
C
21H23N2OPS
C20H20FN2OPS
386.41
382.44
Crystal system
T (K)
monoclinic
173(2)
monoclinic
173(2)
k (Å)
Space group
0.71073
C2/c
0.71073
C2/c
a (Å)
b (Å)
c (Å)
34.0424(18)
5.3111(3)
21.7373(13)
96.905(3)
3901.7(4)
8
33.983(2)
Scheme 2. Synthesis of N,N0-dibenzylthiophosphorodiamidate derivatives.
5.1838(3)
21.5614(14)
93.471(3)
3791.3(4)
8
b (°)
V (Å3)
Z
Dcalc (g/cm3)
1.302
1.354
Reflections collected
No. of independent reflections
Goodness-of-fit (GOF)
13016
4703
1.041
14404
5105
1.045
Final R indices [(I > 2
r
(I)]
R1 = 0.0456
wR1 = 0.1132
R1 = 0.0721
wR1 = 0.1268
R1 = 0.0484
wR1 = 0.1367
R1 = 0.0743
wR1 = 0.1620
R indices (all data)
P
P
P
P
R1
=
|F0| ꢁ |Fc|/ |F0|, wR2 = [ (F02 ꢁ Fc2)2/ w(F02)2]1/2
.
Fig. 1. Molecular structure of 6; thermal ellipsoids were drawn at 30% probability
level.
The 1H NMR of compounds 6–10 reveal the presence of all ex-
pected signals in the expected ratio of integration and broad sig-
nals corresponding to the –NH moiety appeared in the range of
3–3.5 ppm, which was more deshielded than N,N0-dibenzylphosp-
horodiamidate. The benzylic protons appear as a complex multi-
plet in 6–10 as a result of coupling with the neighboring –NH
Scheme 1. Synthesis of arylthiophosphodichloridate derivatives.
spectroscopic techniques. The 1H NMR of compounds 1–5 contains
all the signals for structural moieties in the expected ratio. 13C
NMR reveals that the phenyl carbon atom directly bonded to oxy-
gen is considerably deshielded with respect to the other aromatic
peaks with the exception of compound 2 where the aromatic car-
bon atom attached to fluorine atom, is even further deshielded.
Compounds 1–5 showed a sharp signal in their 31P NMR as ex-
pected from the structures. The 31P of arylthiophosphodichlori-
dates is more deshielded (approximately 45 ppm) [49], as
compared to the arylphosphorodichloridates. Unlike arylphospho-
rodichloridates, these compounds are quite stable in moisture and
air.
The reactivity of arylphosphorodichloridates and arylthiophos-
phodichloridates can be rationalized on the basis of the electroneg-
ativity difference between oxygen (3.44) and sulfur (2.58) atoms.
In case of arylphosphorodichloridates, the more electronegative
oxygen makes the phosphorous center more electrophilic as com-
pared to the sulfur in arylthiophosphodichloridates. Conclusively,
the nucleophilic attack is more feasible on the phosphorous center
of arylphosphorodichloridates, and ease of nucleophilic attack is
the responsible phenomenon for the difference in reactivity. Prob-
ably this was the reason for the sluggish aminiation reaction (step-
II) under ambient temperature.
2
proton and phosphorus with JP–N = 11.9 Hz. The expected signals
appeared in the 13C NMR spectra. The 31P NMR of compounds
6–10 reveals a single peak at ca. 65 ppm that is ca. 17 ppm deshield-
ed with respect to the parent thiophosphodichloridates. In the IR
spectra, the presence of tN–H, tP@S and tP–N peaks appeared with
prominent intensities for compounds 6–10. The structural identity
of these compounds was determined by using HRMS. The unambig-
uous structural analysis was performed by studying the single
crystal X-ray structures of compounds 6 and 7 (Figs. 1 and 2).
To analyze the behavior of N,N0-dibenzylthiophosphorodiami-
dates towards ZnCl2, compounds 6–10 were treated with ZnCl2 in
1:1 stoichiometric ratio. The reaction was performed in THF under
reflux conditions to obtain the product (Scheme 3) and the vola-
tiles were removed under reduced pressure. In fact, the reaction
was very slow at ambient temperature. These observations prove
that the N,N0-dibenzylthiophosphorodiamidates are not as reactive
as N,N0-dibenzylphosphorodiamidates. The 1H NMR analysis of
reaction mixtures revealed that the –NH signal disappeared com-
pletely and signals corresponding to BnNH2 were seen. The reac-
tion did not proceed in the absence of ZnCl2 or when perfectly
anhydrous conditions were used. The results indicate clearly that
there is P–N bond cleavage that is assisted by ZnCl2. Compounds
11–15 were isolated in good yields using the aforementioned
method. The spectral characteristics of the hydrolyzed products
(11–15) are almost similar to the respective N,N0-dibenzylthio-
phosphorodiamidate. The 31P of compounds 11–15 were more
The N,N0-dibenzylthiophosphorodiamidate derivatives (6–10),
were synthesized by treating the corresponding arylthiophospho-
rodichloridates (1–5) with benzylamine in toluene (Scheme 2) at
80 °C. In this step excess benzylamine acts as scavenger for HCl.
After aqueous work up, these compounds were purified by column
chromatography and isolated in 70–75% yield as pale yellow to
white solids.
shielded (
horodiamidate.
D
dP = 1–3 ppm) than the parent N,N0-dibenzylthiophosp-

P. Malik, D. Chakraborty / Polyhedron 52 (2013) 831–836
835
N,N0-dibenzylthiophosphorodiamidates have shown similar behav-
ior as N,N0-dibenzylphosphorodiamidates towards ZnCl2 and P–N
bond hydrolyzed products were obtained. The propensity of hydro-
lysis is higher for the phosphorodiamidates derivatives.
Acknowledgements
The authors thank the Department of Science and Technology,
New Delhi, for financial support.
Appendix A. Supplementary data
It consists of spectroscopic characterization spectra of all com-
pounds described. CCDC 876224 and 876225 contain the supple-
mentary crystallographic data for 6 and 7. These data can be
obtained free of charge via http://www.ccdc.cam.ac.uk/conts/
retrieving.html, or from the Cambridge Crystallographic Data Cen-
tre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: (+44) 1223-336-
033; or e-mail: deposit@ccdc.cam.ac.uk.
Fig. 2. Molecular structure of 7; thermal ellipsoids were drawn at 30% probability
level.
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These compounds were obtained in good yields with high purity.

836
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