A simple and effective approach to the via one-pot reactions in water

Article abstract of DOI:10.1080/10426507.2010.494168

Chemical Equation Presented Water-accelerated synthesis of organic target molecules has been used as a key method for the preparation of phosphoryloxy phosphonate derivatives. Condensation reactions of acid chlorides with dialkyl (aryl) phosphites in the

Full text of DOI:10.1080/10426507.2010.494168

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Phosphorus, Sulfur, and Silicon and the
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A Simple and Effective Approach to the
Via One-Pot Reactions in Water
Abolfazl Hosseini a , Mohammad A. Khalilzadeh b , Sara Hallajian b
Mahmood Tajbakhsh a
&
a Department of Organic Chemistry, Faculty of Chemistry ,
Mazandaran University , Babolsar, Iran
b Department of Chemistry, Islamic Azad University , Qaemshahr
Branch , Qaemshahr, Iran
Published online: 19 Feb 2011.
To cite this article: Abolfazl Hosseini , Mohammad A. Khalilzadeh , Sara Hallajian & Mahmood
Tajbakhsh (2011) A Simple and Effective Approach to the Via One-Pot Reactions in Water, Phosphorus,
Sulfur, and Silicon and the Related Elements, 186:2, 225-232, DOI: 10.1080/10426507.2010.494168
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Phosphorus, Sulfur, and Silicon, 186:225–232, 2011
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426507.2010.494168
A SIMPLE AND EFFECTIVE APPROACH TO THE VIA
ONE-POT REACTIONS IN WATER
Abolfazl Hosseini,1 Mohammad A. Khalilzadeh,2
Sara Hallajian,2 and Mahmood Tajbakhsh1
1Department of Organic Chemistry, Faculty of Chemistry, Mazandaran University,
Babolsar, Iran
2Department of Chemistry, Islamic Azad University, Qaemshahr Branch,
Qaemshahr, Iran
GRAPHICAL ABSTRACT
O
P
N
R
O
P
O
N
Me
R'
R'
O
O
R'
P
O
2
O
+
H
O
R
Cl
O
R'
O
H2O, 50oC, 30-45 min
O
R'
R'
R'
3
2
1
Yield % of 3
1, 3
a
R
4-Me-C6H4
4-Cl-C6H4
4-Br-C6H4
4-NO2-C6H4
Ph
Ph
Ph
Ph
87
b
c
85
90
83
92
89
86
d
e
Ph
Ph
Ph
Ph
Et
f
g
4-OMe-C6H4
h
i
4-Me-C6H4
90
78
Et
Me
Et
Et
j
Et
tBu
tBu
Me
Et
75
74
k
l
Abstract Water-accelerated synthesis of organic target molecules has been used as a key
method for the preparation of phosphoryloxy phosphonate derivatives. Condensation reactions
of acid chlorides with dialkyl (aryl) phosphites in the presence of N-methyl imidazole in water
have been developed as efficient and clean green synthetic procedures for the preparation of
phosphoryloxy phosphonates in high yields. This synthetic protocol provides rapid access to
novel and diversely substituted phosphoryloxy phosphonate derivatives.
Keywords Acid chloride; dialkyl (aryl) phosphate; N-methyl imidazole; one-pot reactions;
phosphoryloxy phosphonates
INTRODUCTION
Phosphorus compounds containing the P–C bond are not particularly frequent in
nature; however, they have diverse biological activities and have attracted considerable
Received 28 February 2010; accepted 12 May 2010.
Address correspondence to Mohammad A. Khalilzadeh, Department of Chemistry, Islamic Azad University,
Qaemshahr Branch, P. O. Box 163, Qaemshahr, Iran. E-mail: m.Khalilzadeh@hotmail.com
225

226
A. HOSSEINI ET AL.
synthetic and pharmacological interest.1,2 Besides valuable applications, their use in the
production of the dangerous compounds sarin-, soman-, and VX-type chemical warfare
agents (CWAs) must be noted.3 Phosphonates have important applications in flame re-
tardance,4,5 organic synthesis,6 and in biology.7,8 Phosphonates also have been used as
substitutes of the corresponding esters and acids of high biological activity9,10 and as con-
venient probes for designing antibodies on the basis of transition state models. Addition of
the phosphate–phosphonate compound as a flame retardant for polyurethanes or polyesters
results in suitable flexibility and flame retardance.11–13 Hence, a large number of meth-
ods have appeared describing novel syntheses of phosphonate systems.14–17 In addition,
performing organic reactions in water has become highly attractive in recent years due to
environmental considerations.18
As part of our current studies on the development of new routes in the synthesis of
organic compounds, we report an efficient synthetic route to phosphoryloxy phosphonate
derivatives. Thus, the reaction of acid chlorides 1 with dialkyl (aryl) phosphites 2 in the
presence of N-methyl imidazole in water leads to phosphoryloxy phosphonate derivatives
3 in good yield (Scheme 1).
O
P
R
N
O
P
N
Me
O
R'
O
O
R'
R'
O
P
O
O
+
2
H
O
H2O, 50 oC, 30-45 min
R'
Cl
R
O
O
R'
R'
2
3
1
R'
Yield % of 3
1, 3
a
R
4-Me-C6H4
4-Cl-C6H4
4-Br-C6H4
4-NO2-C6H4
Ph
Ph
Ph
Ph
87
b
c
85
90
83
92
89
86
d
e
Ph
Ph
Ph
Ph
Et
f
g
4-OMe-C6H4
h
i
4-Me-C6H4
90
78
75
75
74
Et
Me
Et
Et
tBu
tBu
j
Et
k
l
Me
Et
Scheme 1 Synthesis of phosphoryloxy phosphonate derivatives.
RESULTS AND DISCUSSION
The starting point for our experiments was to optimize the reaction conditions. Thus,
after testing different reaction conditions, it was found that upon simple mixing of acid
chlorides (5 mmol), dialkyl (aryl) phosphite (4 mmol), and N-methyl imidazole (4 mmol),

SYNTHESIS OF PHOSPHONATE PHOSPHATES
227
a quantitative conversion to phosphoryloxy phosphonate derivatives was observed with
excellent yields in water. In addition, the reaction of acid chlorides and dialkyl (aryl)
phosphite does not perform without N-methyl imidazole. However, the reaction of acid
chlorides 1 with dialkyl (aryl) phosphites 2 in the presence of N-methyl imidazole in water
leads to phosphoryloxy phosphonate derivatives 3 in excellent yields (Scheme 1). The
product 3l is a known compound.17 The structures of compounds 3a–3l were determined
on the basis of their 1H, 13C, 31P NMR, and IR spectra as well as elemental analysis data.
The 1H NMR spectrum of 3a in CDCl3 exhibited one singlet for the methyl protons at δ =
2.36 ppm and one doublet of doublets at δ = 6.11 (2JPH = 12.7 Hz and 3JPH = 10.3 Hz) for
the methine proton, along with multiplets at δ = 6.62–7.46 for the aromatic protons. The
13C NMR spectrum of 3a exhibited 32 signals in agreement with the proposed structure.
1
The H decoupled 31P NMR spectrum of 3a displayed two sharp doublets at δ = −10.5
and δ = 7.9 with 3JPP = 40.8 Hz.
Mechanistically, it is reasonable to assume that the reaction involves the initial for-
mation of a 1:1 zwitterionic intermediate 4 between acid chloride and N-methyl imidazole,
which undergoes reaction with 2 to produce the cation 5 and the anion ion 6 after elimi-
nation of HCl. Intermediate 5 would be attacked by the negatively charged 6 and would
lose N-methyl imidazole to produce 7. This would be attacked by the negatively charged
species 6 again, and finally compound 3 would be formed in good yield17,19 (Scheme 2).
_
O
R'
2
N
Cl
_
O
1
Me
N
+
+
Me
N
+
N
Me
P
_
N
R
N
+
R
HCl
R'
O
O
6
O
5
4
_
_
O
O
O
R
O
O
R
P
O
P
R'
N
P
R'
_
N
Me
R
P
R'
R'
O
O
O
O
P
O
O
6
R'
R'
R'
O
R'
O
O
O
O
O
R'
R'
7
8
9
O
R
O
P
R'
R'
_
R'
O
3
O
O
P
O
R'
O
10
Scheme 2 Proposed mechanism for synthesis of phosphoryloxy phosphonates.
Because of the release of HCl during the reaction, a small quantity of N-methyl
imidazole is protonated as the reaction proceeds. Also, decomposition of an insignificant
quantity of the acid chloride occurs on the reaction timescale. For these reasons, an excess
of N-methyl imidazole and of the acid chloride is used in these reactions.
Clearly, the results show that the reaction between acid chlorides and dialkyl (aryl)
phosphites in the presence of N-methyl imidazole provides a simple one-pot entry into
the synthesis of phosphoryloxy phosphonate derivatives of potential synthetic and phar-
macological interest. The present method carries the advantage of being performed under

228
A. HOSSEINI ET AL.
one-pot conditions, and requires no activation or modification of the educts. In addition,
phosphoryloxy phosphonate derivatives using commercially available starting materials are
synthesized.
EXPERIMENTAL
N-Methyl imidazole, acid chlorides, and dialkyl (aryl) phosphite were obtained from
Fluka and were used without further purification. Melting points were measured on an
Electrothermal 9100 apparatus. Elemental analyses for C, H, and N were performed using
a Heraeus CHN–O-Rapid analyzer. Mass spectra were recorded on a Finnigan-Matt 8430
spectrometer operating at an ionization potential of 70 eV. IR spectra were measured on a
Shimadzu IR-460 spectrophotometer. 1H, 13C, and 31P NMR spectra were measured with a
Bruker DRX-500 Avance spectrometer at 500.1, 125.8, and 202.4 MHz, respectively. 1H,
13C, and 31P spectra were obtained for solutions in CDCl3 using TMS as internal standard
and 85% H3PO4 as external standard, respectively.
Preparation of Compounds 3: General Procedure
N-Methyl imidazole (4 mmol) was added slowly to a mixture of the acid chloride
1 (5 mmol) and the repective dialkyl (aryl) phosphites 2 (4 mmol). Then, water (5 mL)
was added to the reaction mixture, and the mixture was heated for 12 h at 50◦C. After
completion of the reaction (30–45 min) as indicated by TLC (n-hexane:EtOAc, 8:1), the
resulting solid was removed by filtration, washed with water (5 mL) and diethylether
(1 mL), and dried to afford the pure title compound. The dried product thus obtained
showed a single spot on TLC and was pure enough for all analytical purposes.
Diphenyl[(diphenoxyphosphoryl)oxy](4-methylphenyl)methyl]phosphonate
(3a)
White powder, mp 150–152◦C; yield: 1.01 g (87%). IR (KBr) (νmax/cm−1): 1510,
1
1324, 1295, 1248, and 1100. H NMR (500.1 MHz, CDCl3): δ = 2.36 (s, 3H, Me), 6.11
(dd, 2JPH = 12.7 Hz, 3JPH = 10.3 Hz, 1H, CH), 6.62–7.28 (m, 22H, CH), 7.46 (d, 3J = 7.8
Hz, 2H, CH). 13C NMR (125.7 MHz, CDCl3): δ = 21.3 (Me), 76.0 (dd, 1JPC = 175.2 Hz,
2JPC = 7.2 Hz, CH), 120.0 (d, 3JPC = 4.8 Hz, CH), 120.1 (d, 3JPC = 4.7 Hz, CH), 120.4 (d,
3JPC = 4.4 Hz, CH), 120.5 (d, 3JPC = 4.1 Hz, CH), 125.2 (CH), 125.3 (CH), 125.4 (CH),
3
128.5 (CH), 128.6 (CH), 129.3 (CH), 129.4 (CH), 129.6 (d, JPC = 4.2 Hz, CH), 129.7
(CH), 139.6 (dd, 2JPC = 8.5 Hz, 3JPC = 3.4 Hz), 139.7, 150.1 (d, 2JPC = 9.0 Hz), 150.2 (d,
2JPC = 9.2 Hz), 150.3 (d, 2JPC = 7.8 Hz), 150.5 (d, 2JPC = 7.6 Hz). 31P NMR (202 MHz,
CDCl3): δ = −10.5 (d, 3JPP = 40.8 Hz), 7.9 (d, 3JPP = 40.8 Hz). MS: m/z (%) = 586 (M+,
15), 495 (48), 353 (64), 246 (58), 233 (100), 91 (68), 77 (47). Anal. Calcd. for C32H28O7P2
(586.41): C, 65.53; H, 4.81. Found: C, 65.38; H, 4.75%.
Diphenyl[(diphenoxyphosphoryl)oxy](4-chlorophenyl)methyl]phosphonate
(3b)
Pale yellow powder, mp 158–160◦C; yield: 1.03 g (85%). IR (KBr) (νmax/cm−1):
1
2
1587, 1462, 1387, 1290 and 1157. H NMR (500.1 MHz, CDCl3): δ = 6.09 (dd, JPH
=
13.2 Hz, 3JPH = 10.5 Hz, 1H, CH), 6.92–7.28 (m, 22 CH), 7.47 (d, 3J = 6.7 Hz, 2H, CH).
13C NMR (125.7 MHz, CDCl3): δ = 74.9 (dd, 1JPC = 178.3 Hz, 2JPC = 6.8 Hz, CH), 119.8

SYNTHESIS OF PHOSPHONATE PHOSPHATES
229
(d, 3JPC = 4.8 Hz, CH), 120.1 (d, 3JPC = 4.5 Hz, CH), 120.3 (d, 3JPC = 4.6 Hz, CH), 120.4
3
(d, JPC = 4.3 Hz, CH), 125.3 (CH), 125.4 (CH), 125.5 (CH), 128.9 (CH), 129.6 (CH),
129.7 (CH), 129.8 (CH), 129.9 (d, 3JPC = 4.5 Hz, CH), 130.4 (CH), 135.7 (dd, 2JPC = 8.6
Hz, 3JPC = 4.2 Hz), 139.7, 150.0 (d, 2JPC = 10.2 Hz), 150.1 (d, 2JPC = 10.2 Hz, C), 150.3
(d, 2JPC = 8.2 Hz). 31P NMR (202 MHz, CDCl3): δ = −11.8 (d, 3JPP = 39.9 Hz), 7.7 (d,
3JPP = 39.8 Hz). MS: m/z (%) = 606 (M+, 20), 497 (68), 373 (74), 233 (100), 109 (52),
91 (45), 77 (78). Anal. Calcd. for C31H25ClO7P2 (606.93): C, 61.35; H, 4.15. Found: C,
61.28; H, 4.12%.
Diphenyl[[diphenoxyphosphoryl)oxy](4-bromophenyl)methyl]phosphonate
(3c)
White powder, mp 165–167◦C; yield: 1.17 g (90%). IR (KBr) (νmax/cm−1): 1554,
1
2
1410, 1384, 1298. 1147 and 1025. H NMR (500.1 MHz, CDCl3): δ = 6.84 (dd, JPH
=
14.5 Hz, 3JPH = 10.9 Hz, 1H, CH), 6.99–7.41 (m, 22H, CH), 7.52 (d, 3J = 7.4 Hz, 2H, CH).
13C NMR (125.7 MHz, CDCl3): δ = 78.4 (dd, 1JPC = 182.5 Hz, 2JPC = 8.4 Hz, CH), 118.4
(d, 3JPC = 5.2 Hz, CH), 119.7 (d, 3JPC = 5.7 Hz, CH), 120.1 (d, 3JPC = 4.9 Hz, CH), 121.7
3
(d, JPC = 4.8 Hz, CH), 125.1 (CH), 125.3 (CH), 125.4 (CH), 129.2 (CH), 129.4 (CH),
3
2
129.5 (CH), 129.7 (CH), 129.9 (d, JPC = 6.2 Hz, CH), 130.1 (CH), 132.8 (dd, JPC
=
9.4 Hz, 3JPC = 5.8 Hz, C), 138.6 (C), 149.8 (d, 2JPC = 9.8 Hz, C), 150.0 (d, 2JPC = 9.8 Hz,
C), 151.4 (d, 2JPC = 8.7 Hz, C). 31P NMR (202 MHz, CDCl3): δ = −9.8 (d, 3JPP = 38.8
Hz), 8.5 (d, 3JPP = 38.5 Hz). Anal. Calcd. for C31H25BrO7P2 (651.39): C, 57.16; H, 3.87.
Found: C, 57.14; H, 3.86%.
Diphenyl[[diphenoxyphosphoryl)oxy](4-nitrophenyl)methyl]phosphonate
(3d)
Yellow powder, mp 174–176◦C; yield: 1.02 g (83%). IR (KBr) (νmax/cm−1): 1524,
2
1478, 1356, 1289, 1145 and 1087. 1H NMR (500.1 MHz, CDCl3): δ = 6.25 (dd, JPH
=
3
3
14.3 Hz, JPH = 10.7 Hz, 1H, CH), 6.98–7.32 (m, 20H, CH), 7.66 (d, J = 8.5 Hz, 2H,
CH), 8.12 (d, 3J = 8.5 Hz, 2H, CH). 13C NMR (125.7 MHz, CDCl3): δ = 74.8 (dd, 1JPC
=
2
3
3
181.3 Hz, JPC = 6.7 Hz, CH), 119.8 (d, JPC = 5.1 Hz, CH), 120.1 (d, JPC = 4.8 Hz,
CH), 120.3 (d, 3JPC = 4.1 Hz, CH), 123.6 (d, 3JPC = 4.2 Hz, CH), 125.7 (CH), 125.8 (CH),
3
126.4 (CH), 129.0 (CH), 129.1 (CH), 129.8 (CH), 129.9 (CH), 130.0 (d, JPC = 7.4 Hz,
CH), 131.0 (CH), 132.5 (dd, 2JPC = 10.2 Hz, 3JPC = 6.4 Hz, C), 148.4 (d, 2JPC = 8.7 Hz,
C), 149.8 (C), 149.9 (d, 2JPC = 9.6 Hz, C), 150.0 (d, 2JPC = 8.5 Hz, C), 150.3 (d, 2JPC
8.6 Hz, C). 31P NMR (202 MHz, CDCl3): δ = −10.3 (d, 3JPP = 40.2 Hz), 12.4 (d, 3JPP
=
=
40.2 Hz). Anal. Calcd. for C31H25NO9P2 (617.48): C, 60.30; H, 4.08; N, 2.27. Found: C,
60.27; H, 3.94; N, 2.18%.
Diphenyl[[diphenoxyphosphoryl)oxy](phenyl)methyl]phosphonate (3e)
Yellow powder, mp 142–144◦C; yield: 1.05 g (92%). IR (KBr) (νmax/cm−1): 1541,
1
2
1487, 1456, 1358, 1290 and 1148. H NMR (500.1 MHz, CDCl3): δ = 6.16 (dd, JPH
=
13.0 Hz, JPH = 10.4 Hz, 1H, CH), 6.73–7.38 (m, 25H, CH). 13C NMR (125.7 MHz,
3
1
2
3
CDCl3): δ = 76.1 (dd, JPC = 176.5 Hz, JPC = 6.7 Hz, CH), 120.1 (d, JPC = 6.2 Hz,

230
A. HOSSEINI ET AL.
CH), 120.2 (d, 3JPC = 5.8 Hz, CH), 120.4 (d, 3JPC = 4.7 Hz, CH), 121.5 (d, 3JPC = 4.7 Hz,
CH), 125.4 (CH), 125.6 (CH), 128.5 (CH), 128.6 (CH), 128.7 (CH), 128.9 (CH), 129.6 (d,
3JPC = 6.8 Hz, CH), 129.7 (CH), 129.9 (CH), 131.7 (dd, 2JPC = 10.8 Hz, 3JCP = 5.7 Hz,
C), 150.0 (d, 2JPC = 9.4 Hz, C), 150.1 (d, 2JPC = 9.2 Hz, C), 150.3 (d, 2JPC = 8.7 Hz, C),
150.5 (d, 2JPC = 9.5 Hz, C). 31P NMR (202 MHz, CDCl3): δ = −11.7 (d, 3JPP = 40.1 Hz),
8.4 (d, 3JPP = 40.1 Hz). Anal. Calcd. for C31H26O7P2 (572.49): C, 65.49; H, 4.58. Found:
C, 65.38; H, 4.48%.
Diphenyl[[diphenoxyphosphoryl)oxy]propyl]methyl]phosphonate (3f)
Yellow powder,mp 154–156◦C; yield: 0.93 g (89%). IR (KBr) (νmax/cm−1): 1654,
1
3
1547, 1325, 1245, 1189 and 1048. H NMR (500.1 MHz, CDCl3): δ = 1.16 (t, J = 7.2
Hz, 3H, CH3), 2.18 (m, 2H, CH2), 5.22 (m, 1H, CH), 6.79–7.37 (m, 20H, CH). 13C NMR
(125.7 MHz, CDCl3): δ = 9.9 (d, 2JPC = 10.7 Hz, CH3), 24.6 (dd, 2JPC = 14.2 Hz, 3JPC
=
8.4 Hz, CH2), 75.6 (dd, 1JPC = 171.6 Hz, 2JPC = 7.4 Hz, CH2), 120.1 (d, 3JPC = 6.5 Hz,
CH), 120.2 (d, 3JPC = 6.8 Hz, CH), 120.5 (d, 3JPC = 5.7 Hz, CH), 120.7 (d, 3JPC = 5.8 Hz,
CH), 125.5 (CH), 125.7 (CH), 129.4 (CH), 129.7 (CH), 129.8 (CH), 128.9 (CH), 149.9
(d, 2JPC = 10.4 Hz, C), 150.1 (d, 2JPC = 10.3 Hz, C), 150.4 (d, 2JPC = 9.8 Hz, C), 150.5
(d, 2JPC = 9.5 Hz, C). 31P NMR (202 MHz, CDCl3): δ = −10.2 (d, 3JPP = 39.0 Hz), 9.5
(d, 3JPP = 39.1 Hz). Anal. Calcd. for C27H26O7P2 (524.44): C, 61.84; H, 5.00. Found: C,
61.74; H, 4.87%.
Diphenyl[[diphenoxyphosphoryl)oxy](4-methoxyphenyl)methyl]
phosphonate (3g)
White powder, mp 158–160◦C; yield: 1.03 g (86%). IR (KBr) (νmax/cm−1): 1525,
1455, 1324, 1247 and 1187. 1H NMR (500.1 MHz, CDCl3): δ = 3.54 (s, 3H, OCH3), 6.24
(dd, 2JPH = 12.5 Hz, 3JPH = 10.4 Hz, 1H, CH), 6.54–7.36 (m, 20H, CH), 7.52 (d, 3J = 7.5
3
Hz, 2H, CH), 7.64 (d, J = 7.3 Hz, 2H, CH). 13C NMR (125.7 MHz, CDCl3): δ = 52.4
1
2
3
(OCH3), 68.8 (dd, JPC = 185.4 Hz, JPC = 9.5 Hz, CH), 120.1 (d, JPC = 4.8 Hz, CH),
121.2 (d, 3JPC = 4.7 Hz, CH), 121.9 (d, 3JPC = 4.4 Hz, CH), 122.4 (d, 3JPC = 4.1 Hz, CH),
126.3 (CH), 126.8 (CH), 127.0 (CH), 128.6 (CH), 129.1 (CH), 129.7 (CH), 130.0 (CH),
130.1 (d, 3JPC = 6.3 Hz, CH), 130.2 (CH), 140.2 (dd, 2JPC = 8.5 Hz, 3JPC = 3.4 Hz, C),
152.2 (d, 2JPC = 8.9 Hz, C), 152.6 (d, 2JPC = 8.9 Hz, C), 152.8 (d, 2JPC = 7.9 Hz, C), 153.0
(d, 2JPC = 8.1 Hz, C), 158.8 (C). 31P NMR (202 MHz, CDCl3): δ = −11.2 (d, 3JPP = 38.4
Hz), 8.54 (d, 3JPP = 38.4 Hz). Anal. Calcd. for C32H28O8P2 (602.51): C, 63.79; H, 4.64.
Found: C, 63.64; H, 4.58%.
Diethyl[[diethoxyphosphoryl)oxy](4-methylphenyl)methyl]phosphonate (3f)
White powder, mp 165–167◦C; yield: 0.64 g (90%). IR (KBr) (νmax/cm−1): 1524,
1487, 1347, 1310 and 1298. 1H NMR (500.1 MHz, CDCl3): δ = 1.25 (t, 3JHH = 7.2 Hz,
6H, CH3), 1.35 (t, 3JHH = 7.4 Hz, 6H, CH3), 2.37 (s, 3H, CH3), 4.25 (m, 2H, CH2), 4.28
(m, 2H, CH2), 4.45 (m, 2H, CH2), 4.47 (m, 2H, CH2), 6.27 (dd, 2JPH = 14.3 Hz, 3JPH
=
11.5 Hz, 1H, CH), 7.36 (d, 3JHH = 8.5 Hz, 2H, CH), 8.24 (d, 3JHH = 8.4 Hz, 2H, CH). 13
C
3
3
NMR (125.7 MHz, CDCl3): δ = 13.4 (d, JPC = 5.6 Hz, CH3), 14.6 (d, JPC = 6.4 Hz,
2
2
CH3), 22.3 (CH3), 62.1 (d, JPC = 8.5 Hz, CH2), 62.3 (d, JPC = 8.6 Hz, CH2), 62.5 (d,

SYNTHESIS OF PHOSPHONATE PHOSPHATES
231
2JPC = 7.4 Hz, CH2), 62.7 (d, 2JPC = 7.6 Hz, CH2), 75.6 (dd, 1JPC = 187.4 Hz, 2JPC = 9.7
Hz, CH), 129.4 (d, 3JPC = 6.8 Hz, CH), 129.7 (d, 3JPC = 6.7 Hz, CH), 131.8 (CH), 132.0
(CH), 132.8 (dd, 2JPC = 9.5 Hz, 3JPC = 4.7 Hz, C), 140.1 (C). 31P NMR (202 MHz, CDCl3):
3
3
δ = −12.0 (d, JPP = 38.4 Hz), 10.3 (d, JPP = 38.4 Hz). Anal. Calcd. for C16H28O7P2
(394.34): C, 48.73; H, 7.16. Found: C, 48.65; H, 6.98%.
Dimethyl[[dimethoxyphosphoryl)oxy]propyl]phosphonate (3i)
Yellow powder, mp 115–117◦C; yield: 0.43 g (78%). IR (KBr) (νmax/cm−1): 1541,
1487, 1452, 1328, and 1254. 1H NMR (500.1 MHz, CDCl3): δ = 1.28 (m, 3H, CH3), 1.65
(m, 2H, CH2), 3.72 (d, 3JPH = 5.4 Hz, 3H, CH3), 3.78 (d, 3JPH = 5.6 Hz, 3H, CH3), 3.80
3
3
(d, JPH = 6.2 Hz, 3H, CH3), 3.82 (d, JPH = 6.2 Hz, 3H, CH3), 5.24 (m, 1H, CH). 13C
NMR (125.7 MHz, CDCl3): δ = 12.5 (d, 3JPC = 4.8 Hz, CH3), 28.3 (dd, 2JPC = 7.4 Hz,
3JPC = 4.2 Hz, CH2), 51.4 (d, 2JPC = 6.0 Hz, OCH3), 51.8 (d, 2JPC = 6.2 Hz, OCH3), 52.0
2
2
1
(d, JPC = 5.8 Hz, OCH3), 52.3 (d, JPC = 5.8 Hz, OCH3), 78.4 (dd, JPC = 195.2 Hz,
2JPC = 9.7 Hz, CH). 31P NMR (202 MHz, CDCl3): δ = −11.7 (d, 3JPP = 34.5 Hz), 12.3
3
(d, JPP = 34.5 Hz). Anal. Calcd. for C7H18O7P2 (276.16): C, 30.44; H, 6.57. Found: C,
30.34; H, 6.40%.
Diethyl[[diethoxyphosphoryl)oxy]propyl]phosphonate (3j)
Pale yellow powder, mp 121–123◦C; yield: 0.50 g (75%). IR (KBr) (νmax/cm−1):
1537, 1462, 1447, 1320 and 1212. 1H NMR (500.1 MHz, CDCl3): δ = 1.25–1.27 (m, 3H,
CH3), 1.32 (t, 3JHH = 7.2 Hz, 3H, CH3), 1.36 (t, 3JHH = 7.2 Hz, 3H, CH3), 1.40 (t, 3JHH
=
7.3 Hz, 3H, CH3), 1.42 (t, 3JHH = 7.3 Hz, 3H, CH3), 1.62–1.64 (m, 1H, CH), 1.75–1.77 (m,
1H, CH), 4.25–4.27 (m, 2H, OCH2), 4.28–4.30 (m, 2H, OCH2), 4.35–4.37 (m, 2H, OCH2),
4.40–4.42 (m, 2H, OCH2), 4.82–4.85 (m, 1H, CH). 13C NMR (125.7 MHz, CDCl3): δ =
12.3 (d, 3JPC = 4.5 Hz, CH3), 15.2 (d, 3JPC = 5.0 Hz, CH3), 15.3 (d, 3JPC = 5.0 Hz, CH3),
3
3
2
16.4 (d, JPC = 4.8 Hz, CH3), 16.5 (d, JPC = 4.8 Hz, CH3), 26.5 (dd, JPC = 8.2 Hz,
3JPC = 5.4 Hz, CH2), 62.2 (d, 2JPC = 8.7 Hz, OCH2), 62.3 (d, 2JPC = 8.7 Hz, OCH2), 63.4
2
2
1
(d, JPC = 8.5 Hz, OCH2), 63.5 (d, JPC = 8.5 Hz, OCH2), 74.6 (dd, JPC = 187.4 Hz,
2JPC = 9.2 Hz, CH). 31P NMR (202 MHz, CDCl3): δ = −11.5 (d, 3JPP = 34.2 Hz), 11.3
(d, 3JPP = 34.2 Hz). Anal. Calcd. for C11H26O7P2 (332.27): C, 39.76; H, 7.89. Found: C,
39.65; H, 7.78%.
Di(tert-butyl)[[(dimethoxyphosphoryl)oxy]2,2-dimethylpropyl]phosphonate
(3k)
White powder, mp 111–113◦C; yield: 0.46 g (75%). IR (KBr) (νmax/cm−1): 1557,
1480, 1467, 1334 and 1228. 1H NMR (500.1 MHz, CDCl3): δ = 1.14 (s, 9H, Me3C), 3.74
(d, 3JPH = 5.5 Hz, 3H, CH3), 3.76 (d, 3JPH = 5.5 Hz, 3H, CH3), 3.82 (d, 3JPH = 5.8 Hz,
3H, CH3), 3.85 (d, 3JPH = 5.8 Hz, 3H, CH3), 5.22 (dd, 3JPH = 5.8 Hz, 3JPH = 4.2 Hz, 1H,
CH). 13C NMR (125.7 MHz, CDCl3): δ = 28.7 (d, 3JPC = 5.6 Hz, Me3C), 34.6 (2JPC = 8.5
Hz, 3JPC = 5.0 Hz, Me3C), 52.3 (d, 2JPC = 7.4 Hz, OCH3), 52.5 (d, 2JPC = 7.4 Hz, OCH3),
53.4 (d, 2JPC = 8.0 Hz, OCH3), 53.5 (d, 2JPC = 8.0 Hz, OCH3), 80.4 (dd, 1JPC = 194.3 Hz,
2JPC = 8.6 Hz, CH). 31P NMR (202 MHz, CDCl3): δ = −12.0 (d, 3JPP = 35.1 Hz), 11.5
3
(d, JPP = 35.1 Hz). Anal. Calcd. for C9H22O7P2 (304.21): C, 35.53; H, 7.29. Found: C,
35.58; H, 7.32%.

232
A. HOSSEINI ET AL.
Di(tert-butyl)[[(diethoxyphosphoryl)oxy]2,2-dimethylpropyl]
phosphonate (3l)
White powder, mp 115–117◦C; yield: 0.53 g (74%). IR (KBr) (νmax/cm−1): 1562,
1480, 1475, 1345 and 1260. 1H NMR (500.1 MHz, CDCl3): δ = 1.14 (s, 9H, Me3C), 1.28
3
3
3
(t, JHH = 7.2 Hz, 3H, CH3), 1.30 (t, JHH = 7.2 Hz, 3H, CH3), 1.32 (t, JHH = 7.3 Hz,
3
3H, CH3), 1.34 (t, JHH = 7.3 Hz, 3H, CH3), 4.06–4.10 (m, 2H, OCH2), 4.12–4.15 (m,
2H, OCH2), 4.17–4.20 (m, 2H, OCH2), 4.23–4.27 (m, 2H, OCH2), 4.45 (dd, 3JPH = 11.7
Hz, 3JPH = 8.5 Hz, 1H, CH). 13C NMR (125.7 MHz, CDCl3): δ = 15.7 (d, 3JPC = 4.6 Hz,
CH3), 15.8 (d, 3JPC = 4.6 Hz, CH3), 16.4 (d, 3JPC = 5.2 Hz, CH3), 16.5 (d, 3JPC = 5.2 Hz,
CH3), 29.4 (d, 3JPC = 5.4 Hz, Me3C), 35.1 (dd, 2JPC = 8.9 Hz, 3JPC = 6.0 Hz, Me3C), 61.8
(d, 2JPC = 8.5 Hz, OCH2), 62.2 (d, 2JPC = 8.5 Hz, OCH2), 62.5 (d, 2JPC = 8.7 Hz, OCH2),
63.6 (d, 2JPC = 8.7 Hz, OCH2), 74.6 (dd, 1JPC = 150.2 Hz, 2JPC = 7.0 Hz, CH). 31P NMR
(202 MHz, CDCl3): δ = −11.5 (d, 3JPP = 15.5 Hz), 19.6 (d, 3JPP = 15.5 Hz). Anal. Calcd.
for C13H30O7P2 (360.32): C, 43.33; H, 8.39. Found: C, 43.42; H, 8.42%.
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