New phosphoroamidate compounds: Synthesis, structural characterization and studies on ZnCl2 assisted hydrolysis of the P-N bond

Article abstract of DOI:10.1016/j.poly.2010.04.002

A variety of phosphorodiamidate compounds were synthesized from the corresponding phosphorodichloridate intermediates and phosphorus oxychloride. These were completely characterized using different spectroscopic methods and single crystal X-ray diffraction studies on one of them. Studies revealed that water in the presence of a mild Lewis acid like ZnCl₂ was found to assist the hydrolysis of the P-N linkage. The proof of this concept was effectively realized through the hydrolysis of hexamethylphosphoramide.

Full text of DOI:10.1016/j.poly.2010.04.002

Polyhedron 29 (2010) 2142–2148
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Polyhedron
journal homepage: www.elsevier.com/locate/poly
New phosphoroamidate compounds: Synthesis, structural characterization
and studies on ZnCl2 assisted hydrolysis of the P–N bond
*
Payal Malik, Debashis Chakraborty , Venkatachalam Ramkumar
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
Article history:
A variety of phosphorodiamidate compounds were synthesized from the corresponding phosphorodi-
chloridate intermediates and phosphorus oxychloride. These were completely characterized using
different spectroscopic methods and single crystal X-ray diffraction studies on one of them. Studies
revealed that water in the presence of a mild Lewis acid like ZnCl2 was found to assist the hydrolysis
of the P–N linkage. The proof of this concept was effectively realized through the hydrolysis of
hexamethylphosphoramide.
Received 16 November 2009
Accepted 8 April 2010
Available online 24 April 2010
Keywords:
Phosphorodichloridate
Dibenzylphosphorodiamidate
Zinc chloride
Ó 2010 Elsevier Ltd. All rights reserved.
Hydrolysis
Hexamethylphosphoramide
1. Introduction
phonic acids have been implicated as insecticides and sterilizing
agents [24] whereas diphosphonic acids have been found useful
Organophosphorus chemistry is indeed intriguing and spans a
variety of research areas which include chemical synthesis, studies
on their coordination chemistry with different metals and their
role in biomedicine [1]. The chemistry of organophosphorus com-
pounds has been a popular research area because of their applica-
tions in agriculture [2], pharmaceuticals [3–8], biology [9,10] and
chemical agents [11–17]. Organic phosphines, phosphites, phos-
phinites and amidophosphinites are widely used in homogeneous
catalysis as ligands in transition-metal complexes. The very exis-
tence of this area, which is of primary importance in today’s chem-
istry, especially in its infancy, was due to the use of phosphine
complexes of palladium, platinum, rhodium, etc. The use of transi-
tion-metal complexes with chiral phosphine ligands [18–20] as
catalysts is of particular interest when performing asymmetric
hydrogenation, hydroformylation and many other reactions. These
catalysts enabled the syntheses of enantiomerically pure com-
pounds, including the most important pharmaceutical derivatives.
Phosphorus containing polymers possess valuable properties, such
as fire resistance and inertness to chemical reagents, which make
them interesting from a practical point of view [21,22]. Organo-
phosphorus compounds find extensive use in synthetic organic
chemistry. This primarily includes well-known olefination reac-
tions: Wittig reaction and P–O olefination that is, the reaction of
phosphorus-containing carbanions with carbonyl compounds
(Horner–Woodward–Emmons reaction) [23]. Some organophos-
for anti inflammatory and pain easing activities [25]. Phosphoram-
idate compounds containing N-phosphorylated amino acids have
been particularly useful for their antiviral, antitumor and anti
HIV properties [26–29]. Quantum chemical calculations on their
structure [30,31] and spectroscopic properties [32–34] of these
have revealed interesting conclusions. We were inspired to venture
into the chemistry of phosphorodiamidates for their potential use
as ligands in the coordination chemistry with transition-metals
[35–38]. In this regard, we have developed a general route towards
the synthesis of various N,N0-dibenzylphosphorodiamidates. These
compounds were anticipated to provide bidentate ligating envi-
ronment with different metal synthons. However, the P–N bond
is moderately polar and susceptible to attack by nucleophiles. A
simple nucleophile like water in the presence of a mild Lewis acid
like ZnCl2 was found to cleave this linkage. The work presented is a
reflection of our understanding in this context.
2. Experimental
2.1. General methods
The reactions concerning the synthesis of phosphorodichlori-
dates and phosphoroamidates were performed under dry argon
atmosphere using standard Schlenk techniques with rigorous
exclusion of moisture and air. Toluene and tetrahydrofuran (THF)
were dried by heating under reflux over sodium and benzophe-
none and distilled fresh prior to use. All the phenols used in this
* 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 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.poly.2010.04.002

P. Malik et al. / Polyhedron 29 (2010) 2142–2148
2143
study along with phosphorous oxychloride, hexamethylphospho-
ramide (HMPA) and zinc chloride were purchased from Aldrich
and used without subsequent purification. Toluene, hexane, ethyl
acetate, methylene chloride, chloroform and tetrahydrofuran were
purchased from Ranchem India. CDCl3 used for NMR spectral mea-
surements was purchased from Aldrich. For the spectral character-
ization of phosphorodichloridates, the CDCl3 used was dried over
calcium hydride and distilled.
2.3.4. 4-MeC6H4OP(O)Cl2 (4)
The compound 4 was synthesized from 4-MeC6H4OH (1.0 g,
9.2 mmol), POCl3 (5.6 g, 36.8 mmol) and LiCl (8.7 mg, 0.2 mmol).
Yield = 1.3 g (60%). 1H NMR (400 MHz, CDCl3, ppm): d 7.18–7.14
(m, 4H, ortho, meta), 2.31 (s, 3H, ArMe). 13C NMR (100 MHz CDCl3,
ppm): d 147.57 (Ar–O), 137.06 (Ar–C), 130.75 (Ar–Me), 120.30 (Ar–
C), 20.76 (Ar–Me). 31P{1H} NMR (161 MHz CDCl3, ppm): d 3.57 (s).
GC–MS: 224.30 (M+H)+. Anal. Calc. for C7H7Cl2O2P: C, 37.37; H,
3.14. Found: C, 37.51; H, 3.22%.
2.2. Instrumentation
2.3.5. 4-t-BuC6H4OP(O)Cl2 (5)
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-
The compound 5 was synthesized from 4-tBuC6H4OH (1.0 g,
6.8 mmol), POCl3 (4.2 g, 27.2 mmol) and LiCl (8.4 mg, 0.2 mmol).
Yield = 1.1 g (62%). 1H NMR (400 MHz, CDCl3, ppm): d 7.43 (d,
2H, meta), 7.19 (d, 2H, ortho), 1.31 (s, 9H, Ar–CMe3). 13C NMR
(100 MHz CDCl3, ppm):
d 150.21 (Ar–O), 147.38 (Ar–CMe3),
127.03 (Ar–C), 119.84 (Ar–C), 34.55 (CMe3), 31.29 (CMe3). 1P{1H}
NMR (161 MHz CDCl3, ppm): d 3.59 (s). GC–MS: 267.36 (M+H)+.
Anal. Calc. for C10H13Cl2O2P: C, 44.97; H, 4.91. Found: C, 45.26; H,
4.69%.
ple were recorded on
a Micro mass 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.
2.4. Synthesis of N,N0-dibenzylphosphorodiamidates (6–10)
An aryl phosphorodichloridate and benzylamine in a stoichiom-
etric ratio 1:4 were stirred for 12 h in toluene (10 mL) under
ambient conditions to produce the corresponding N,N0-dibenzyl-
phosphorodiamidate. The reaction mixture was quenched with
water and extracted with methylene chloride. Removal of the vol-
atiles gave the crude product which was subsequently purified by
column chromatography (70% of chloroform in hexane as eluent)
and obtained as a white solid after removal of volatiles.
2.3. Synthesis of phosphorodichloridates (1–5)
The required phenol was stirred under reflux with phosphorous
oxychloride in the stoichiometric ratio 1:4 and catalytic amount of
lithium chloride. The reaction was monitored using TLC (5% ethyl
acetate in hexane) against the required phenol. The time required
for completion of the reaction was found to be 24 h for 1, 4 and 5
and 48 h for 2 and 3. The reaction mixture was purified by distilling
the excess POCl3 under reduced pressure to yield the phosphorod-
ichloridates as colorless viscous liquids.
2.4.1. 2-MeC6H4OP(O)(NHBn)2 (6) (Bn = PhCH2–)
The compound 6 was synthesized from 1 (0.45 g, 2 mmol) and
BnNH2 (0.86 g, 8 mmol). Yield = 0.4 g (60%). M.p. = 53 °C. IR (neat,
cmꢀ1): 3377 (N–H), 1223 (P@O), 697 (P–N). 1H NMR (400 MHz,
CDCl3, ppm): d 7.44–7.06 (m, 14H, ortho, meta, para), 4.21 (m,
4H, CH2Bn), 3.22 (br, 2H, NH), 2.23 (s, 3H, ArMe). 13C NMR
(100 MHz CDCl3, ppm): d 149.79 (Ar–O), 139.64 (Ar–C), 129.03
(Ar–C), 128.40 (Ar–C), 127.36 (Ar–C), 127.28 (Ar–C), 127.19 (Ar–
Me), 126.90 (Ar–C), 124.11 (Ar–C), 119.83 (Ar–C), 45.25 (CH2Ph),
16.50 (Ar–Me). 31P{1H} NMR (161 MHz CDCl3, ppm): d 10.96. HRMS
(ESI) for C21H23N2O2P (M+H)+: Calc., 367.1575; Found: 367.1577.
2.3.1. 2-MeC6H4OP(O)Cl2 (1)
The compound 1 was synthesized from 2-MeC6H4OH (1.0 g,
9.2 mmol), POCl3 (5.6 g, 36.8 mmol) and LiCl (8.7 mg, 0. 2 mmol).
Yield = 1.2 g (56%). 1H NMR (400 MHz, CDCl3, ppm): d 7.34–7.20
(m, 4H, ortho, meta, para), 2.35 (s, 3H, ArMe). 13C NMR (100 MHz
CDCl3, ppm): d 148.84 (Ar–O), 132.03 (Ar–C), 129.49 (Ar–C),
127.43 (Ar–Me), 126.94 (Ar–C), 120.04 (Ar–C), 16.32 (Ar–Me).
31P{1H} NMR (161 MHz CDCl3, ppm): d 3.44 (s). GC–MS: 224.76
(M+H)+. Anal. Calc. for C7H7Cl2O2P: C, 37.37; H, 3.14. Found: C,
37.54; H, 3.08%.
2.4.2. 2-FC6H4OP(O)(NHBn)2 (7)
The compound 7 was synthesized from 2 (0.46 g, 2 mmol) and
BnNH2 (0.86 g, 8 mmol). Yield = 0.4 g (53%). M.p. = 48 °C. IR (neat,
cmꢀ1): 3199 (N–H), 1260 (P@O), 692 (P–N). 1H NMR (400 MHz,
CDCl3, ppm): d 7.38–7.05 (m, 14H, ortho, meta, para), 4.18 (m,
4H, CH2Bn), 3.05 (br, 2H, NH). 13C NMR (100 MHz CDCl3, ppm): d
158.23 (Ar–F), 155.17 (Ar–O), 139.49 (Ar–C), 128.77 (Ar–C),
127.50 (Ar–C), 125.49 (Ar–C), 124.73 (Ar–C), 123.30 (Ar–C),
116.86 (Ar–C), 45.35 (CH2Ph). 31P{1H} NMR (161 MHz CDCl3,
ppm): d 11.24. HRMS (ESI) for C20H20FN2O2P (M+Na)+: Calc.,
393.1144; Found: 393.1140.
2.3.2. 2-FC6H4OP(O)Cl2 (2)
The compound 2 was synthesized from 2-FC6H4OH (1.0 g,
8.9 mmol), POCl3 (5.5 g, 35.6 mmol) and LiCl (8.4 mg, 0. 2 mmol).
Yield = 1.1 g (50%). 1H NMR (400 MHz, CDCl3, ppm): d 7.43–7.17
(m, 4H, ortho, meta, para). 13C NMR (100 MHz CDCl3, ppm): d
154.65 (Ar–F), 148.80 (Ar–O), 128.44 (Ar–C), 125.12 (Ar–C),
122.84 (Ar–C), 117.74 (Ar–C). 31P{1H} NMR (161 MHz CDCl3,
ppm):
d
3.01 (s). GC–MS: 228.15 (M+H)+. Anal. Calc. for
C6H4Cl2FO2P: C, 31.47; H, 1.76. Found: C, 31.68; H, 1.44%.
2.3.3. 2-ClC6H4OP(O)Cl2 (3)
2.4.3. 2-ClC6H4OP(O)(NHBn)2 (8)
The compound 3 was synthesized from 2-ClC6H4OH (1.0 g,
7.8 mmol), POCl3 (4.8 g, 31.2 mmol) and LiCl (8.4 mg, 0.2 mmol).
Yield = 1 g (50%). 1H NMR (400 MHz, CDCl3, ppm): d 7.51–7.28
(m, 4H, ortho, meta, para). 13C NMR (100 MHz CDCl3, ppm): d
145.94 (Ar–O), 131.27 (Ar–C), 128.28 (Ar–C), 127.97 (Ar–Cl),
125.92 (Ar–C), 121.92 (Ar–C). 31P{1H} NMR (161 MHz CDCl3,
The compound 8 was synthesized from 3 (0.49 g, 2 mmol) and
BnNH2 (0.86 g, 8 mmol). Yield = 0.4 g (51%). M.p. = 70 °C. IR (neat,
cmꢀ1): 3229 (N–H), 1259 (P@O), 702 (P–N). 1H NMR (400 MHz,
CDCl3, ppm): d 7.57–7.13 (m, 14H, ortho, meta, para), 4.24 (m,
4H, CH2Bn), 3.17 (br, 2H, NH). 13C NMR (100 MHz CDCl3, ppm): d
146.92 (Ar–O), 138.75 (Ar–C), 130.68 (Ar–C), 128.71 (Ar–C),
128.07 (Ar–C), 127.66 (Ar–C), 127.53 (Ar–C), 126.04 (Ar–Cl),
125.79 (Ar–C), 122.03 (Ar–C), 45.91 (CH2Ph). 31P{1H} NMR
ppm):
C6H4Cl3O2P: C, 29.36; H, 1.64. Found: C, 29.65; H, 1.77%.
d
4.05 (s). GC–MS: 245.06 (M+H)+. Anal. Calc. for

2144
P. Malik et al. / Polyhedron 29 (2010) 2142–2148
(161 MHz CDCl3, ppm): d 11.09. HRMS (ESI) for C20H20ClN2O2P
7.33–7.11 (m, 9H, ortho, meta, para), 4.21 (m, 2H, CH2Ph), 3.89 (s,
5H, THF and OH), 2.15 (s, 3H, Ar–Me), 1.90 (s, 4H, THF). 13C NMR
(100 MHz CDCl3, ppm): d 148.84 (Ar–O), 138.34 (Ar–C), 131.63
(Ar–C), 128.88 (Ar–C), 128.77 (Ar–C), 127.69 (Ar–C), 127.38 (Ar–
C), 127.30 (Ar–Me), 125.26 (Ar–C), 119.83 (Ar–C), 69.28 (THF),
45.32 (CH2Ph), 25.48 (THF), 16.62 (Ar–Me). 31P{1H} NMR
(161 MHz CDCl3, ppm): d 13.18. HRMS (ESI) for C14H18NO4P
(M+THF)+: Calc., 367.1549; Found: 367.1553.
(M+Na)+: Calc., 409.0849; Found: 409.0845.
2.4.4. 4-MeC6H4OP(O)(NHBn)2 (9)
The compound 9 was synthesized from 4 (0.45 g, 2 mmol) and
BnNH2 (0.86 g, 8 mmol). Yield = 0.5 g (63%). M.p. = 65 °C. IR (neat,
cmꢀ1): 3198 (N–H), 1200 (P@O), 690 (P–N). 1H NMR (400 MHz,
CDCl3, ppm): d 7.31–7.10 (m, 14H, ortho, meta, para), 4.18 (m,
4H, CH2Bn), 2.98 (br, 2H, NH), 2.31 (s, 3H, ArMe). 13C NMR
(100 MHz CDCl3, ppm): d 148.89 (Ar–O), 139.58 (Ar–C), 134.18
(Ar–Me), 130.23 (Ar–C), 128.74 (Ar–C), 127.61 (Ar–C), 120.23
(Ar–C), 45.39 (CH2Ph), 20.83 (Ar–Me). 31P{1H} NMR (161 MHz
CDCl3, ppm): d 10.96. HRMS (ESI) for C21H23N2O2P (M+H)+: Calc.,
367.1575; Found: 367.1581.
2.6.2. [2-FC6H4OP(O)O(OH)][BnNH3] (13)
The compound 13 was synthesized from 7 (0.10 g, 0.27 mmol)
and ZnCl2 (36 mg). Yield = 56 mg (70%). IR (neat, cmꢀ1): 3302 (N–
H), 1202 (P@O), 693 (P–N). 1H NMR (400 MHz, CDCl3, ppm): d
7.29–7.09 (m, 9H, ortho, meta, para), 4.19 (m, 2H, CH2Ph), 3.91
(br, 1H, OH). 13C NMR (100 MHz CDCl3, ppm): d 151.01 (Ar–F),
138.48 (Ar–O), 138.42 (Ar–C), 128.81 (Ar–C), 127.69 (Ar–C),
126.26 (Ar–C), 125.01 (Ar–C), 123.29 (Ar–C), 116.89 (Ar–C), 45.26
(CH2Ph). 31P{1H} NMR (161 MHz CDCl3, ppm): d 13.75. HRMS
(ESI) for C13H15FNO4P (M+THF)+: Calc., 371.1298; Found: 371.1290.
2.4.5. 4-t-BuC6H4OP(O)(NHBn)2 (10)
The compound 10 was synthesized from 5 (0.53 g, 2 mmol) and
BnNH2 (0.86 g, 8 mmol). Yield = 0.6 g (72%). M.p. = 40 °C. IR (neat,
cmꢀ1): 3174 (N–H), 1203 (P@O), 690 (P–N). 1H NMR (400 MHz,
CDCl3, ppm): d 7.24–7.05 (m, 14H, ortho, meta, para), 4.11 (m,
4H, CH2Bn), 2.79 (br, 2H, NH), 1.25 (s, 9H, Ar–CMe3). 13C NMR
2.6.3. [2-ClC6H4OP(O)O(OH)][BnNH3] (14)
(100 MHz CDCl3, ppm):
d
148.79 (Ar–O), 147.46 (Ar–CMe3),
The compound 14 was synthesized from 8 (0.10 g, 0.25 mmol)
and ZnCl2 (35 mg). Yield = 55 mg (70%). IR (neat, cmꢀ1): 3378 (N–
H), 1260 (P@O), 692 (P–N). 1H NMR (400 MHz, CDCl3, ppm): d
7.43–7.10 (m, 9H, ortho, meta, para), 5.05 (s, 1H, OH), 4.37 (m,
2H, CH2Ph), 3.95 (s, 4H, THF), 1.96 (s, 4H, THF). 13C NMR
(100 MHz CDCl3, ppm): d 152.04 (Ar–O), 137.28 (Ar–C), 128.70
(Ar–C), 127.78 (Ar–C), 127.34 (Ar–C), 127.03 (Ar–C), 126.96 (Ar–
C), 124.92 (Ar–Cl), 122.55 (Ar–C), 117.16 (Ar–C), 69.47 (THF),
45.36 (CH2Ph), 25.37 (THF). 31P{1H} NMR (161 MHz CDCl3, ppm):
d 13.62. Anal. Calc. for C17H23ClNO5P: C, 52.65; H, 5.98; N, 3.61.
Found: C, 52.45; H, 6.37; N, 3.99%.
139.61 (Ar–C), 128.71 (Ar–C), 127.62 (Ar–C), 127.45 (Ar–C),
126.63 (Ar–C), 119.90 (Ar–C), 45.38 (CH2Ph), 34.46 (Ar–CMe3),
31.55 (Ar–CMe3). 31P{1H} NMR (161 MHz CDCl3, ppm): d 11.25.
HRMS (ESI) for C24H29N2O2P (M+H)+: Calc., 409.2045; Found:
409.2048.
2.5. Synthesis of 4-t-Buphenyl N,N0-di–methylbenzylphosphorodi-
amidate (11)
A stirred solution of 5 (1.34 g, 5 mmol) in 10 mL toluene was re-
acted with ( )-a-methylbenzylamine (3.03 g, 25 mmol) under
ambient conditions for 12 h. The reaction mixture was quenched
with water and extracted with methylene chloride. Removal of
the volatiles gave the crude product which was subsequently puri-
fied by column chromatography (60% of chloroform in hexane as
eluent) and obtained as a colorless viscous solid after removal of
volatiles.
2.6.4. [4-MeC6H4OP(O)O(OH)][BnNH3] (15)
The compound 15 was synthesized from 9 (0.10 g, 0.27 mmol)
and ZnCl2 (37 mg). Yield = 42 mg (70%). IR (neat, cmꢀ1): 3302 (N–
H), 1202 (P@O), 694 (P–N). 1H NMR (400 MHz, CDCl3, ppm): d
7.31–7.28 (m, 9H, ortho, meta, para), 4.18 (m, 2H, CH2Ph), 3.90 (s,
5H, THF and OH), 2.30 (s, 3H, Ar–Me), 1.92 (s, 4H, THF). 13C NMR
(100 MHz CDCl3, ppm): d 148.64 (Ar–O), 142.30 (Ar–C), 138.47
(Ar–Me), 135.12 (Ar–C), 130.40 (Ar–C), 128.78 (Ar–C), 127.56
(Ar–C), 120.18 (Ar–Me), 69.13 (THF), 45.25 (CH2Ph), 25.52 (THF),
20.81 (Ar–Me). 31P{1H} NMR (161 MHz CDCl3, ppm): d 13.44. HRMS
(ESI) for C14H18NO4P (M+THF)+: Calc., 367.1549; Found: 367.1548.
Yield = 1.8 g (81%). IR (neat, cmꢀ1): 3199 (N–H), 1213 (P@O),
696 (P–N). 1H NMR (400 MHz, CDCl3, ppm): d 7.29–6.99 (m, 14H,
ortho, meta, para), 4.53 (q, 2H, CHMe), 3.18 (br, 1H, NH), 2.99 (br,
1H, NH), 1.43 (d, 6H, CHMe), 1.30 (s, 9H, ArtBu). 13C NMR
(100 MHz CDCl3, ppm):
d 148.95 (Ar–O), 147.01 (Ar–CMe3),
145.17 (Ar–C), 128.62 (Ar–C), 127.09 (Ar–C), 126.38 (Ar–C),
125.94 (Ar–C), 119.78 (Ar–C), 51.39 (CHMe), 34.36 (Ar–CMe3),
31.53 (Ar–CMe3), 25.34 (CHMe). 31P{1H} NMR (161 MHz CDCl3,
ppm):
437.2358; Found: 437.2355.
2.6.5. [4-t-BuC6H4OP(O)O(OH)][BnNH3] (16)
The compound 16 was synthesized from 10 (0.10 g, 0.24 mmol)
and ZnCl2 (33 mg). Yield = 58 mg (70%). IR (neat, cmꢀ1): 3316 (N–
H), 1211 (P@O), 695 (P–N). 1H NMR (400 MHz, CDCl3, ppm): d
7.34–7.04 (m, 9H, ortho, meta, para), 4.22 (m, 2H, CH2Ph), 3.89 (s,
5H, THF and OH), 1.90 (s, 4H, THF), 1.29 (s, 9H, Ar–CMe3). 13C
NMR (100 MHz CDCl3, ppm): d 148.14 (Ar–O), 147.89 (Ar–C),
138.67 (Ar–CMe3), 138.42 (Ar–C), 128.73 (Ar–C), 127.54 (Ar–C),
126.79 (Ar–C), 119.70 (Ar–C), 68.30 (THF), 45.19 (CH2Ph), 34.46
(Ar–CMe3), 31.48 (Ar–CMe3), 25.68 (THF). 31P{1H} NMR (161 MHz
CDCl3, ppm): d 13.66. HRMS (ESI) for C17H24NO4P (M+THF)+: Calc.,
409.2018; Found: 409.2016.
d 8.70. HRMS (ESI) for C
26H33N2O2P (M+H)+: Calc.,
2.6. Synthesis of phosphonic acid anion (12–17)
To
stirred solution of N,N0-dibenzylphosphorodiamidate/
a
HMPA in THF (10 mL) was added ZnCl2 under ambient conditions
in a stoichiometric ratio 1:1. The time required for completion of
the reaction was found to be 12 h for 12, 15–17 and 24 h for 13
and 14. The solvent was removed under reduced pressure and
the reaction mixture was extracted with toluene and subsequently
filtered. Evaporation of the solvent yielded the crude product
which was purified by crystallization from 1:1 methylene chloride
and hexane mixture at 0 °C.
2.6.6. [Me2NP(O)O(OH)][Me2NH2] (17)
HMPA (0.10 g, 0.56 mmol) and ZnCl2 (76 mg) were used.
Yield = 70 mg (75%). IR (neat, cmꢀ1): 3360 (N–H), 1181 (P@O). 1H
NMR (400 MHz, CDCl3, ppm): d 3.89 (s, 4H, THF), 2.62 (br, 12H,
NMe), 1.89 (s, 4H, THF). 13C NMR (100 MHz CDCl3, ppm): d 69.13
(THF), 36.78 (NMe), 25.36 (THF). 31P{1H} NMR (161 MHz CDCl3,
ppm): d 27.85. Anal. Calc. for C8H23N2O4P: C, 39.66; H, 9.57; N,
11.56. Found: C, 40.01; H, 9.39; N, 11.41%.
2.6.1. [2-MeC6H4OP(O)O(OH)][BnNH3] (12)
The compound 12 was synthesized from 6 (0.10 g, 0.23 mmol)
and ZnCl2 (37 mg). Yield = 42 mg (70%). IR (neat, cmꢀ1): 3306 (N–
H), 1223 (P@O), 696 (P–N). 1H NMR (400 MHz, CDCl3, ppm): d

P. Malik et al. / Polyhedron 29 (2010) 2142–2148
2145
Table 1
These were isolated in moderate yields as colorless viscous liq-
uids after distilling off the excess POCl3. The 1H NMR of 1–5 con-
tains the signals for all moieties in the required ratio. 13C NMR
reveals that the phenyl carbon atom directly bonded to oxygen is
considerably deshielded with respect to the other aromatic peaks
with the exception of 2 where the aromatic carbon atom attached
to fluorine is even further deshielded. These compounds showed
only one signal in their 31P{1H} NMR as expected from the struc-
ture. GC–MS spectra recorded on these compounds reveal the
molecular ion peaks as a proton adduct. Finally, their purity was
assured through the correct elemental analysis values. Reliable IR
spectra could not be obtained as a result of the sensitivity of these
compounds to moisture. These compounds have been reported in
the literature previously where some were prepared by the reac-
tion of the sodium phenolate salt with POCl3 [40] or reaction of
the phenol with POCl3 in the presence of an acid scavenger like
Et3N [41] or direct reaction of phenol with POCl3 in the presence
of NaCl [42]. Our contribution has been in the establishment of a
reliable synthetic route and thorough unambiguous characteriza-
tion of these compounds by various spectroscopic methods.
The N,N0-dibenzylphosphorodiamidate derivatives (6–10) were
synthesized by reacting the corresponding aryl phosphorodichlori-
date (1–5) with benzyl amine in toluene (Scheme 2). These com-
pounds were isolated in 50–70% yield after work up and column
chromatography as white solids.
Crystal data for the structures 10 and 15.
Compound
10
15
Empirical formula
Formula weight
Crystal system
Space group
T (K)
Wavelength (Å)
a (Å)
b (Å)
C
48H58N4O4P2
C28H36N2O8P2
590.53
monoclinic
P21/c
816.92
monoclinic
P21/c
173
173
0.71073
20.8933(8)
9.8712(3)
22.5314(8)
90
99.200(10)
90
4587.1(3)
4
0.71073
12.9529(8)
6.5937(4)
17.3840(11)
90
90.443(3)
90
1484.68(16)
2
c (Å)
a
(°)
b (°)
c
(°)
V (Å3)
Z
Dcalc (g cmꢀ3
)
1.183
31 921
11 178
1.321
10 463
3620
Reflections collected
Number of independent
reflections
Goodness-of-fit (GOF)
1.016
0.979
Final R indices [I > 2
R indices (all data)
r(I)]
R1 = 0.0505,
wR2 = 0.1358
R1 = 0.0914,
wR2 = 0.1676
R1 = 0.0499,
wR2 = 0.1293
R1 = 0.0814,
wR2 = 0.1563
P
P
P
P
R1
=
|Fo| ꢀ |Fc|/ |Fo|, wR2 = [ (F2o ꢀ F2c )2/ w(Fo2)2]1/2
.
The IR spectra of 6–10 reveal peaks due to mN–H, mP@O and mP–N
with prominent intensities. The 1H NMR of 6–10 reveals all the ex-
pected signals in the correct ratio of integration. The benzylic pro-
tons appear as a complex multiplet in 6–10 as a result of coupling
2.7. X-ray crystallography
Single crystals of 10 and 15 suitable for structural studies were
obtained by crystallization from 1:1 methylene chloride/hexane
mixture at 0 °C over a period of one week. X-ray data collection
was performed with Bruker AXS (Kappa Apex 2) CCD diffractome-
2
with the neighboring –NH proton and phosphorus with JP–
N = 11.9 Hz [43]. The aromatic signals of these compounds in the
13C NMR have resemblance to their parent phosphodichloridates.
The 31P{1H} NMR of these 6–10 reveal a single peak at ca.11 ppm
that is downfield shifted ca. 8 ppm with respect to the parent phos-
phodichloridates compounds. The structural identity and the pur-
ity of these compounds were determined using HRMS analysis.
The unambiguous structural analysis was performed by measuring
the single crystal X-ray structure of 10. In a similar manner, com-
ter equipped with graphite monochromated Mo (K
radiation source. The data were collected with 100% completeness
for h up to 25°. and u 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 data were reduced for Lorentz and
polarization corrections using SAINT-NT. The multi-scan absorption
correction was applied to the data set. All structures were solved
using SIR-92 and refined using SHELXL-97 [39]. The crystal data are
summarized in Table 1. The non-hydrogen atoms were refined
with anisotropic displacement parameter. All the hydrogen atoms
could be located in the difference Fourier map. The hydrogen
atoms bonded to carbon atoms were fixed at chemically meaning-
ful positions and were allowed to ride with the parent atom during
refinement.
pound 11 was synthesized using 5 and ( )-a-methylbenzylamine.
It is noteworthy to mention that the 1H NMR of this compound
shows two broad signals corresponding to the –NH moiety. Their
authenticity as –NH protons was confirmed using D2O exchange
studies. The 31P{1H} NMR signal is upfield shifted in comparison
to 6–10. This is attributed as a result of electron donation from
the methyl group on the
a carbon atom.
Our initial studies aimed at exploring the reactions of anhy-
drous ZnCl2 with 6–10. These reactions were performed with the
rigorous exclusion of moisture and air in dry THF at ambient tem-
perature. To our surprise, there was no reaction. Such an observa-
tion remained consistent when dioxane was used as a solvent and
the reaction mixture were heated to reflux. This observations may
be rationalized by reasoning that the acidity of the –NH proton is
3. Results and discussion
3.1. Synthesis and characterization
The phosphodichloridates (1–5) were synthesized by heating
various phenols with excess POCl3 in the presence of catalytic
amount of lithium chloride under reflux conditions (Scheme 1).
O
P
O
P
O
LiCl (cat.)
+
4 BnNH2
P
4 POCl3
+
ArOH
ArO
ArO
Cl
NHBn
ArO
Ar =
Cl
Cl
BnHN
Cl
2-MeC6H4
2-FC6H4
1
2
3
4
5
2-MeC6H4
2-FC6H4
6
7
Ar =
2-ClC6H4
4MeC6H4
4-tBuC6H4
2-ClC6H4
4MeC6H4
4-tBuC6H4
8
9
10
Scheme 1. Synthesis of phosphodichloridates.
Scheme 2. Synthesis of N,N0-dibenzylphosphorodiamidate.

2146
P. Malik et al. / Polyhedron 29 (2010) 2142–2148
lower than that of the –OH proton. Interestingly, when such reac-
tion mixtures were exposed to air over prolonged periods of time, a
white precipitate appeared. Analysis of such reaction mixtures
using 1H NMR after removal of volatiles clearly revealed that some
definite change may have taken place. The –NH signal disappeared
completely. 1H NMR signals corresponding to BnNH2 was seen.
These observations prompted us to reinvestigate these reactions
under ordinary conditions by using regular reagent grade THF that
was not dried previously and exposing them to air. The initial clear
solution containing the reactants became slightly turbid. The vola-
tiles were removed and 1H of the reaction mixture had the same
characteristics as before. In each case the results were identical
resulting in a puzzle. This mystery was solved by treatment of 9
with ZnCl2 and isolating the product. This was subsequently crys-
tallized using methylene chloride/hexane mixture at 0 °C and sub-
jected to single crystal X-ray diffraction studies. Our understanding
has been depicted in Scheme 3.
It is clear that there is cleavage of the P–N bond which is as-
sisted by mild Lewis acid like ZnCl2, leading to the formation of
phosphonic acid. Literature reports such a P–N bond cleavage ini-
tiated by strong mineral acids under reflux conditions [44,45]. It
is also believed that the P–N bond can be cleaved using Pd salts
where the product is not as simple as this [46]. Our method may
be considered superior since the transformation is brought about
using an environmentally benign cheap salt like ZnCl2, in the com-
plete absence of mineral acids.
O
P
ArO
NHBn
BnHN
anhyd. ZnCl2
anhyd.THF
Compounds 12–16 were isolated in good yields using the
above method. The spectral characteristics are similar to those ob-
served for the N,N0-dibenzylphosphorodiamidate precursors 6–10,
respectively.
O
P
ArO
NHBn
ZnCl2(H2O)X
THF
BnHN
As an application to this concept we decided to carry out a sim-
ilar strategy with HMPA with the hope of cleaving the P–N bond.
To our surprise, we found that the concept was viable and the ex-
pected acid [Me2NP(O)O(OH)][Me2NH2] (17) was isolated in good
yield. This method may be considered a way to detoxify HMPA.
This hydrolysis works equally well with other halide salts of zinc
like ZnBr2 but we preferred ZnCl2 because of its lower cost and ease
of availability. The reaction with other transition-metal divalent
cations like Cu2+, Mn2+ and Ni2+ is extremely slow and appreciable
product could not be isolated under comparable conditions with
ZnCl2.
O
P
-BnNH2
BnNH3
ArO
HO
O
2-MeC6H4 12
Ar =
2-FC6H4
13
14
15
16
2-ClC6H4
4MeC6H4
4-tBuC6H4
Scheme 3. Reaction of N,N0-dibenzylphosphorodiamidate with ZnCl2.
Table 3
Table 2
Selected bond lengths [Å] and bond angles [°] for compound 15.
Selected bond lengths [Å] and bond angles [°] for compound 10.
P(1)–O(1)
P(1)–O(2)
P(1)–O(3)
P(1)–O(4)
O(2)–H(2A)
O(1)–P(1)–O(2)
O(1)–P(1)–O(3)
O(3)–P(1)–O(4)
O(2)–P(1)–O(4)
1.612(16)
1.562(16)
1.497(16)
1.490(14)
0.8270(3)
P(1)–O(1)
P(2)–O(2)
P(1)–N(1)
P(1)–N(2)
N(1)–P(1)–N(2)
O(1)–P(1)–N(2)
O(1)–P(1)–O(2)
O(2)–P(1)–N(1)
1.477(13)
1.607(14)
1.621(18)
1.620(17)
111.91(9)
106.20(8)
113.76(9)
113.80(8)
103.57(8)
103.40(9)
118.15(8)
107.92(9)
Fig. 1. Molecular structure of 10; thermal ellipsoids were drawn at 30% probability level.

P. Malik et al. / Polyhedron 29 (2010) 2142–2148
2147
Fig. 2. Molecular structure of 15; thermal ellipsoids were drawn at 30% probability level.
3.2. Single crystal X-ray diffraction studies
Technology Madras for providing the single crystal X-ray diffrac-
tion facility.
Among the several compounds synthesized in this study, suit-
able crystals for X-ray diffraction studies could be obtained from
10 and 15. Single crystals were grown from dilute solutions of
these compounds in 1:1 methylene chloride/hexane mixture at
0 °C over a period of one week. Compound 10 crystallizes in the
monoclinic space group P21/c with two molecules in the unit cell.
Selected bond lengths and angles are listed in Table 2 and the
molecular structure is depicted in Fig. 1.
As seen from the bond lengths and angles, the phosphorus cen-
ter is in a distorted pyramidal environment. The P@O bond length
is slightly shorter than the P–O length. The P–N bonds are nearly
identical.
Appendix A. Supplementary data
CCDC 750875 and 750876 contain the supplementary crystallo-
graphic data for 10 and 15. These data can be obtained free of
charge via http://www.ccdc.cam.ac.uk/conts/retrieving.html, or
from the Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: (+44) 1223-336-033; or e-mail: de-
posit@ccdc.cam.ac.uk. Supplementary data associated with this
article can be found, in the online version, at doi:10.1016/j.poly.
2010.04.002.
Compound 15 crystallizes in the monoclinic space group P21/c.
Selected bond lengths and angles are given in Table 3 and the
molecular structure is depicted in Fig. 2.
The bond lengths reveal that the lengths of the P@O and P–O
moieties are almost identical suggesting delocalization in these
bonds. The structure of the anion resembles that of a distorted pyr-
amid. There is interaction between one of the delocalized P–O
bonds and one of the N–H protons of the cation. These are sepa-
rated by 1.954(2) Å.
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This work was supported by Department of Science and Tech-
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under the FIST program, sponsored by the Department of Science
and Technology, New Delhi is gratefully acknowledged. The
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