Microwave-enhanced synthesis of phosphonoacetamides

Article abstract of DOI:10.1080/00397911.2010.530377

An efficient microwave protocol is described for the Michaelis-Arbuzov synthesis of secondary and tertiary N-aryl (and alkyl) (diethylphosphono) acetamides 1, by reaction of chloro- and bromoacetamides with triethyl phosphite in the presence of catalytic

Full text of DOI:10.1080/00397911.2010.530377

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Microwave-Enhanced Synthesis of
Phosphonoacetamides
Nadia Gruber a , María C. Mollo a , Mariana Zani a & Liliana R. Orelli a
a Departamento de Química Orgánica, Facultad de Farmacia y
Bioquímica, CONICET, Buenos Aires, Argentina
Accepted author version posted online: 17 Aug 2011.Published
online: 01 Nov 2011.
To cite this article: Nadia Gruber , María C. Mollo , Mariana Zani & Liliana R. Orelli (2012):
Microwave-Enhanced Synthesis of Phosphonoacetamides, Synthetic Communications: An International
Journal for Rapid Communication of Synthetic Organic Chemistry, 42:5, 738-746
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Synthetic Communications1, 42: 738–746, 2012
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2010.530377
MICROWAVE-ENHANCED SYNTHESIS OF
PHOSPHONOACETAMIDES
´
Nadia Gruber, Marıa C. Mollo, Mariana Zani, and
Liliana R. Orelli
Departamento de Quımica Organica, Facultad de Farmacia y Bioquımica,
´
CONICET, Buenos Aires, Argentina
´
´
GRAPHICAL ABSTRACT
Abstract An efficient microwave protocol is described for the Michaelis–Arbuzov synthesis
of secondary and tertiary N-aryl (and alkyl) (diethylphosphono)acetamides 1, by reaction
of chloro- and bromoacetamides with triethyl phosphite in the presence of catalytic amounts
of sodium iodide. Remarkable acceleration of the reaction (minutes vs. several hours) over
conventional heating was achieved, together with improved product yields and purity, when
bromoacetamides were employed as the substrates. Chloroacetamides were comparatively
less reactive, leading to satisfactory yields only when a high excess of the reagent was
employed.
Keywords Michaelis–Arbuzov reaction; microwaves; phosphonoacetamides; phosphorus
compounds; sodium iodide
INTRODUCTION
Phosphonoacetamides are interesting because of their capability to complex
different metals. They have found application in the diagnosis and treatment of
several diseases,[1] as extracting agents for alkaline, alkaline earth, and transition
metals,[2] and as reaction catalysts.[3] Some selectively substituted phosphonoaceta-
mides behave as potent inhibitors of carbamylphosphatase, an enzyme involved in
pyrimidine biosynthesis.[4] Such compounds show strong antiproliferative and anti-
tumor activities.[5] In organic synthesis, phosphonoacetamides represent the starting
materials of choice for the preparation of a,b-unsaturated amides, which are versa-
tile synthons.[6] In the course of our research on the LiOH-promoted Horner–
Wadsworth–Emmons reaction,[7] we recently needed to prepare a series of secondary
and tertiary phosphonoacetamides. The preparation of phosphonoacetamides is
Received June 20, 2010.
Address correspondence to Liliana R. Orelli, Departamento de Quımica Organica, Facultad de
´
Farmacia y Bioquımica, CONICET, Junın 956, 1113 Buenos Aires, Argentina. E-mail: lorelli@ffyb.uba.ar
´
´
´
738

SYNTHESIS OF PHOSPHONOACETAMIDES
739
Scheme 1.
generally carried out by nucleophilic displacement of chlorine in chloroacetamides
either by the Michaelis–Arbuzov reaction[8] (thermal path) or by the Michaelis–
Becker reaction[9] (anionic path). N-Alkyl phosphonoacetamides can also be synthe-
sized by aminolysis of phosphonate esters[10] or phosphonoacetic acid.[11] Two
alternative methodologies have also been reported, namely reaction between an
a-phosphonyl carbanion and an isocyanate or a carbamate and condensation of
an amide enolate with diethylchlorophosphate.[12] However, both methods are
actually restricted to the synthesis of a-substituted phosphonoacetamides. The
Michaelis–Arbuzov reaction,[13] which is one of the most versatile pathways for
the formation of carbon–phosphorus bonds,[14] is the most generally employed
strategy. Two disadvantages of this method are that it generally requires an excess
of the reagent[15] and prolonged reaction times (from several hours to days).[16,17]
This may result in partial or total decomposition of sensitive substrates.
Reactions performed under microwave irradiation in general proceed faster,
more cleanly, and with better yields than those performed under conventional heat-
ing.[18] It is widely accepted that reactions involving ionic intermediates are acceler-
ated by microwavaves.[18,19] The mechanism advanced for the Arbuzov reaction[20]
(Scheme 1) involves the formation of a phosphonium salt followed by nucleophilic
displacement and should therefore be improved by microwaves.
Microwave optimization is of special practical interest for reactions involving
prolonged heating at high temperatures. Kiddle et al. reported the microwave-
assisted synthesis of phosphonium salts and phosphonates in pressure tubes.[16,21]
The possibility of employing a microwave oven adapted for reflux heating[22] allows
the reactions to be conducted at controlled (reflux) temperature under atmospheric
pressure, preventing the risk of explosions associated with the use of closed
vessels.[23] Such characteristics, together with the previously mentioned drawbacks
of the conventional Michaelis–Arbuzov method and the lack of an expeditious pro-
cedure for the synthesis of N-arylphosphonoacetamides, prompted us to explore the
use of microwave irradiation to enhance the Michaelis–Arbuzov reaction. We also
investigated the use of sodium and potassium iodides to enhance product yields.
RESULTS AND DISCUSSION
We examined first the reaction between equimolar amounts of N-(4-choloro-
phenyl)chloroacetamide and triethyl phosphite. The results obtained under different
reaction conditions are summarized in Table 1. Under conventional heating, the
reaction (neat) was completed in 10 h, with 59% yield. Under microwave irradiation
at maximum power (700 W), the reaction was remarkably accelerated, while the
product yield was not improved. The possibility of conducting the reaction in
solvent-free conditions on a solid support (Alumina) was also tested (entry 3) but

740
N. GRUBER ET AL.
Table 1. Optimization of the reaction conditions
Molar ratio
Substr.:P(OEt)3
Reaction
time (min)
Power
(Watt)
Yield
(%)a
Entry
X
Solvent
Catalyst
1b
2
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Cl
1:1
1:1
600
1.5
20
–
–
–
–
–
–
700
59
60
3c
4
1:1
1:1
–
350
700
traces
traces
traces
traces
62
15
15
THF
–
5
1:1
1:1
Acetonitrile
DME
DMF
DMF
DMF
DMF
DMF
–
–
700
700
6
15
–
7
1:1
1:1
1.75
1.75
1.75
1.75
1.75
600
2
–
700
700
8
KI
NaI
NaI
NaI
–
64
68
9
1:1
1:2
700
700
10
11
12b
13
14
15
16
17
18
19
20d
21
22
23
72
92
1:4
1:1
700
–
350
68
70
1:1
1:1
–
–
5
10
THF
NaI
NaI
NaI
NaI
NaI
NaI
NaI
–
210
46
45
1:1
1:1
Acetonitrile
DME
DMF
DMF
DMF
DMF
DMF
DMF
DMF
210–350
210–350
210
5
55
91
1:1
2
1:1.5
1:1.5
1:1.5
1:1
1.7
1
210
350
98
97
9
210
210
97
73
2
1:1.5
1:4
2
1.75
–
210
700
75
66
–
aYields correspond to pure compound 1a.
bConventional heating at 110 ꢀC.
cReactants were supported on neutral Alumina.
d5 mmoles of the substrate and 7.5 mmoles of the reagent were employed.
proved to be ineffective. The reaction was then examined employing different sol-
vents (Table 1, entries 4–7). Among them, dimethylformamide was the most efficient,
probably because of its higher dielectric constant and boiling point. In tetrahydro-
furan (THF), acetonitrile, and dimethoxyethane, very low conversion to the desired
product was observed. In previous work, we demonstrated that potassium and
sodium iodides significantly improve the yields of nucleophilic substitutions,[24]
probably because of in situ generation of a more reactive iodoalkyl compound. To
test this hypothesis, we next explored potassium and sodium iodides as catalysts.
A slight improvement in the reaction yield was observed in both cases (entries 8
and 9), and the sodium salt was more efficient. Finally, the use of a large excess
of the reagent was necessary to achieve a good yield of the product (entry 11).
Bearing in mind the relative reactivity of organic halides, which follows the
sequence RI > RBr > RCl,[25] we next turned to the corresponding bromoacetamide

SYNTHESIS OF PHOSPHONOACETAMIDES
741
as the substrate (Table 1). As expected, much lower irradiation powers afforded
comparatively better yields in all the examined conditions (entries 12–17). Complete
conversion of the substrate was achieved with 50% molar excess of the reagent (entry
18). Remarkably, the reaction outcome was similar with irradiation powers from 210
to 350 W (entries 18 and 19) and also when a fivefold amount of the reagents was
employed (entry 20).
To clarify the role of NaI in the outcome of the reactions, we performed some
additional control experiments. In the absence of NaI, only partial conversion to the
desired product was observed for both the bromo and chloroacetamides, even in the
presence of an excess of the reagent (entries 21–23). This confirms the purported
catalytic role of NaI.
Employing the optimized reaction conditions, we synthesized a series of N-
aryl(diethylphosphono)acetamides 1b–g with good yields in very short reaction times
(Table 2, entries 1–6). N-Alkyl derivatives 1h–k (Table 2) were also obtained with
satisfactory yields (entries 7–10).
To further explore the scope of the method, we examined next the synthesis of
N-aryl (and alkyl) tertiary phosphonoacetamides. N,N-Disubstituted bromoaceta-
mides were comparatively less reactive and required a slightly higher irradiation
power to achieve complete conversion. Yields for compounds 1l–o,[26] p,[26,27] and
q[27] were satisfactory and in all cases better than those reported in the literature
synthesized with conventional heating.
Table 2. Microwave-enhanced synthesis of phosphonoacetamides 1
Reaction
time (min)
Power
(Watt)
Entry
Cpd. 1
R1
R2
Yield (%)a
1
2
b
c
C6H5
H
H
H
H
H
H
H
H
H
H
2
210
210
210
210
210
210
210
210
210
210
280
280
280
280
280
280
90
93
4-BrC6H4
4-FC6H4
4-CH3C6H4
1.5
1
3
d
e
94
94
4
1
5
f
4-NO2C6H4
2-CH3C6H4
CH(CH3)C6H5
(CH2)2[3,4-(OCH3)2C6H3]
ter-C4H9
1.5
2
Quant.
84
88
6
g
h
i
7
1.5
2
8
84
81
9
j
2
10
11
12
13
14
15
16
kb
l
CH2C6H5
CH2C6H5
CH2C6H5
CH2C6H5
C6H5
2
87
98
CH3
1.5
1.5
1.5
1.5
1.5
2
m
n
o
p
q
C2H5
iso-C3H7
CH3
84
80
86
91
C6H5
C6H5
C2H5
C6H5
98
aYields correspond to pure compounds.
bDME was employed as the solvent.

742
N. GRUBER ET AL.
CONCLUSIONS
In conclusion, we developed an efficient microwave-based protocol for the
Michaelis–Arbuzov synthesis of phosphonoacetamides 1 by reaction of the corre-
sponding bromoacetamides and triethyl phosphite in the presence of catalytic
amounts of NaI. The method is safe and general, leading to good yields of secondary
and tertiary N-alkyl or aryl derivatives. Its main advantages are the remarkably
short reaction times and the improvement in product yields. No collateral products
arising either from rearrangement of the products or decomposition of the reagent[14]
were observed.
EXPERIMENTAL
1H and 13C NMR spectra were recorded on a Bruker MSL 300-MHz spec-
trometer. Deuteriochloroform was used as the solvent, and the standard concentra-
1
tions of the samples were 10 and 30 mg=mL for H and 13C spectra, respectively.
Chemical shifts are reported in ppm (d) relative to tetramethylsilane (TMS) as an
internal standard. Splitting multiplicities are reported as singlet (s), doublet (d),
double doublet (dd), triplet (t), quartet (q), multiplet (m), and broad signal,
exchangeable (bs ex). Elemental analyses were performed in an Exeter CE 440
(CHNS) elemental analyzer.
General Procedure for Preparation of Diethylphosphonoacetamides
1a–k and 1q
Sodium iodide (0.1 mmol) was added to a solution of the corresponding bro-
moacetamide (1 mmol) and triethylphosphite (1.5 mmol) in dry dimethylformamide
(2 mL). The reaction mixture was intermittently irradiated[28] in a domestic micro-
wave oven (Sanyo EM-D2013) adapted with a reflux condenser. After completion
of the reaction was disclosed by thin-layer chromatography (TLC), the mixture
was diluted with ethyl acetate (50 mL), treated with active charcoal, filtered, and
extracted with water (3 ꢁ 5 mL). The organic phase was dried over sodium sulfate,
filtered, and evaporated in vacuo. The crude products were purified by flash chroma-
tography employing chloroform–ethyl acetate mixtures.
Physical Data and Spectral Characterization of New Compounds
N-(4-Chlorophenyl)diethylphosphonoacetamide (1a). This compound
1
had mp 80–81 ꢀC (from ethyl acetate). H NMR d 9.17 (bs ex, 1H, NH), 7.44 (dd,
J ¼ 8.8 and 3.6 Hz, 2H, aromatics), 7.20 (dd, J ¼ 8.8 and 3.6 Hz, 2H, aromatics),
4.08–4.23 (m, 4H, OCH2), 3.02 (d, J ¼ 20.5 Hz, 2H, CH2P), 1.36 (t, J ¼ 7.1Hz, 6H,
CH3). 13C NMR d 162.32 (d, J ¼ 4.5 Hz), 136.65, 128.51, 128.25, 120.42, 62.88 (d,
J ¼ 6.8 Hz), 36.10 (d, J ¼ 131.1Hz), 16.11 (d, J ¼ 5.6 Hz). Anal. calcd. for
C12H17ClNO4P: C, 47.15; H, 5.61; N, 4.58. Found: C, 47.05; H, 5.63; N, 4.57.
N-(Phenyl)diethylphosphonoacetamide (1b). This compound was
1
obtained as an oil. H NMR d 8.98 (bs ex, 1H, NH), 7.51 (dd, J ¼ 8.7 and 1.1Hz,
2H, aromatics), 7.23–7.30 (m, 2H, aromatics), 7.04–7.09 (m, 1H, aromatics),

SYNTHESIS OF PHOSPHONOACETAMIDES
743
4.13–4.23 (m, 4H, OCH2), 3.03 (d, J ¼ 20.8 Hz, 2H, CH2P), 1.35 (dt, J ¼ 7.2 and
0.5 Hz, 6H, CH3). 13C NMR d 162.47 (d, J ¼ 5.6 Hz), 137.85, 128.36, 123.80,
119.55, 62.68 (d, J ¼ 5.6 Hz), 35.92 (d, J ¼ 131.12 Hz), 15.97 (d, J ¼ 5.6 Hz). Anal.
calcd. for C12H18NO4P: C, 53.14; H, 6.69; N, 5.16. Found: C, 52.92; H, 6.71; N, 5.15.
N-(4-Bromophenyl)diethylphosphonoacetamide (1c). This compound
1
was obtained as an oil. H NMR d 9.21 (bs ex, 1H, NH), 7.39 (d, J ¼ 8.2 Hz, 2H,
aromatics), 7.08 (d, J ¼ 8.2 Hz, 2H, aromatics), 4.08–4.22 (m, 4H, OCH2), 3.01 (d,
J ¼ 20.8 Hz, 2H, CH2P), 1.34 (t, J ¼ 7.1 Hz, 6H, CH3). 13C NMR d 162.41 (d,
J ¼ 4.5 Hz), 137.18, 131.29, 120.88, 116.33, 62.96 (d, J ¼ 5.6 Hz), 36.18 (d,
J ¼ 130.0 Hz), 16.18 (d, J ¼ 5.6 Hz). Anal. calcd. for C12H17BrNO4P: C, 41.16; H,
4.89; N, 4.00. Found: C, 41.24; H, 4.93; N, 3.97.
N-(4-Fluorophenyl)diethylphosphonoacetamide (1d). This compound
1
was obtained as an oil. H NMR d 9.21 (bs ex, 1H, NH), 7.53–7.58 (m, 2H, aro-
matics), 7.03 (dt, J ¼ 8.7 and 1.0 Hz, 2H, aromatics), 4.22–4.30 (m, 4H, OCH2),
3.12 (dd, J ¼ 22.2 and 1.1 Hz, 2H, CH2P), 1.44 (dt, J ¼ 7.0 and 0.8 Hz, 6H, CH3).
13C NMR d 162.27 (d, J ¼ 5.6 Hz), 158.95 (d, J ¼ 243.0 Hz), 134.12 (d, J ¼ 2.3 Hz),
121.15 (d, J ¼ 7.9 Hz), 114.98 (d, J ¼ 2.3 Hz), 62.90 (d, J ¼ 5.6 Hz), 36.03 (d,
J ¼ 130.0 Hz), 16.12 (d, J ¼ 6.8 Hz). Anal. calcd. for C12H17FNO4P: C, 49.83; H,
5.92; N, 4.84. Found: C, 49.65; H, 5.94; N, 4.84.
N-(4-Methylphenyl)diethylphosphonoacetamide (1e). This compound
1
was obtained as an oil. H NMR d 8.87 (bs ex, 1H, NH), 7.48 (d, J ¼ 8.7 Hz, 2H,
aromatics), 7.28 (d, J ¼ 8.7 Hz, 2H, aromatics), 4.12–4.21 (m, 4H, OCH2), 2.99 (d,
J ¼ 20.5 Hz, 2H, CH2P), 1.59 (s, 3H, ArCH3), 1.34 (t, J ¼ 7.0 Hz, 6H, CH3).13C
NMR d 162.33 (d, J ¼ 5.6 Hz), 133.51, 129.07, 119.77, 62.91 (d, J ¼ 6.8 Hz), 36.10
(d, J ¼ 131.1Hz), 20.67, 16.18 (d, J ¼ 6.8 Hz). Anal. calcd. for C13H20NO4P: C,
54.73; H, 7.07; N, 4.91. Found: C, 54.56; H, 7.10; N, 4.90.
N-(4-Nitrophenyl)diethylphosphonoacetamide (1f). This compound had
1
mp 130–131 ꢀC (from ethyl acetate–methanol). H NMR d 9.85 (bs ex, 1H, NH),
8.06 (dd, J ¼ 7.0 and 2.0 Hz, 2H, aromatics), 7.64 (dd, J ¼ 7.0 and 2.0 Hz, 2H, aro-
matics), 4.17–4.26 (m, 4H, OCH2), 3.11 (d, J ¼ 21.3 Hz, 2H, CH2P), 1.39 (t,
J ¼ 7.0 Hz, 6H, CH3). 13C NMR d 163.08 (d, J ¼ 4.5 Hz), 144.07, 142.58, 124.15,
118.46, 63.16 (d, J ¼ 6.8 Hz), 36.29 (d, J ¼ 130.0 Hz), 16.07 (d, J ¼ 6.8 Hz). Anal.
calcd. for C12H17N2O6P: C, 45.58; H, 5.42; N, 8.86. Found: C, 45.50; H, 5.45; N, 8.83.
N-(2-Methylphenyl)diethylphosphonoacetamide (1g). This compound
1
was obtained as an oil. H NMR d 8.68 (bs ex, 1H, NH), 7.85 (d, J ¼ 8.2 Hz, 1H,
aromatics), 7.12–7.22 (m, 2H, aromatics), 7.04–7.09 (m, 1H, aromatics), 4.13–4.23
(m, 4H, OCH2), 3.04 (d, J ¼ 20.5 Hz, 2H, CH2P), 2.31 (s, 3H, ArCH3), 1.35 (t,
J ¼ 7.0 Hz, 6H, CH3). 13C NMR d 162.24 (d, J ¼ 3.4 Hz), 135.55, 130.36, 129.52,
126.38, 125.18, 122.92, 62.86 (d, J ¼ 6.8 Hz), 35.61 (d, J ¼ 130.0 Hz), 17.69, 16.18
(d, J ¼ 6.8 Hz). Anal. calcd. for C13H20NO4P: C, 54.73; H, 7.07; N, 4.91. Found:
C, 54.66; H, 7.10; N, 4.92.
(ꢂ)-N-(1-Phenylethyl)diethylphosphonoacetamide (1h). This compound
1
was obtained as an oil. H NMR d 7.25–7.32 (m, 5H, aromatics), 7.12 (bs ex, 1H,
NH), 5.09 (t, J ¼ 7.0 Hz, 1H, CH), 4.10–4.15 (m, 2H, OCH2), 3.98–4.06 (m, 2H,

744
N. GRUBER ET AL.
OCH2), 2.84 (dd, J ¼ 20.7 and 6.2 Hz, 1H, CHP), 3.83 (dd, J ¼ 20.7 and 12.7 Hz, 1H,
CHP), 1.47 (d, J ¼ 7.0 Hz, 3H, CH3CH), 1.32 (t, J ¼ 7.0 Hz, 3H, CH3), 1.22 (t,
J ¼ 7.0 Hz, 3H, CH3). 13C NMR d 163.02 (d, J ¼ 4.5 Hz), 143.12, 128.36, 127.02,
125.98, 62.06 (d, J ¼ 6.8 Hz), 49.11, 34.95 (d, J ¼ 131.1 Hz), 21.87, 16.07 (d,
J ¼ 6.8 Hz). Anal. calcd. for C14H22NO4P: C, 56.18; H, 7.41; N, 4.68. Found: C,
56.09; H, 7.44; N, 4.65.
N-2-[(3,4-Dimethoxyphenyl)ethyl]diethylphosphonoacetamide (1i). This
compound was obtained as an oil. 1H NMR d 6.73–6.81 (m, 4H, aromatics and NH),
4.03–4.12 (m, 4H, OCH2), 3.87 (s, 3H, OCH3), 3.84 (s, 3H, OCH3), 3.48–3.53 (m,
2H, NCH2), 2.63–2.83 (m, 4H, ArCH2 and CH2P), 1.06 (t, J ¼ 7.1 Hz, 6H, CH3).
13C NMR d 163.63 (d, J ¼ 3.4 Hz), 148.23, 146.88, 130.87, 119.95, 111.36, 110.67,
61.91 (d, J ¼ 5.6 Hz), 59.54, 55.09, 40.65, 34.32 (d, J ¼ 132.2 Hz), 34.38, 15.57 (d,
J ¼ 6.7 Hz). Anal. calcd. for C16H26NO6P: C, 53.48; H, 7.29; N, 3.90. Found: C,
53.38; H, 7.32; N, 3.89.
N-tert-Butyl diethylphosphonoacetamide (1j). This compound was
1
obtained as an oil. H NMR d 6.54 (bs ex, 1H, NH), 4.08–4.15 (m, 4H, OCH2),
2.76 (d, J ¼ 20.5 Hz, 2H, CH2P), 1.34 [s, 9H, C(CH3)3], 1.33 (t, J ¼ 7.0 Hz, 6H,
CH3). 13C NMR d 163.64 (d, J ¼ 3.7 Hz), 63.04 (d, J ¼ 5.4 Hz) 42.7548, 35.81 (d,
J ¼ 130.0 Hz), 28.29, 16.01 (d, J ¼ 6.3 Hz). Anal. calcd. for C10H22NO4P: C, 47.80;
H, 8.83; N, 5.57. Found: C, 47.76; H, 8.87; N, 5.55.
N-Benzyl diethylphosphonoacetamide (1k). This compound was obtained
1
as an oil. H NMR d 7.25–7.34 (m, 5H, aromatics), 7.09 (bs ex, 1H, NH), 4.46 (d,
J ¼ 5.9 Hz, 2H, ArCH2), 4.05–4.15 (m, 4H, OCH2), 2.88 (d, J ¼ 20.5 Hz, 2H,
CH2P), 1.31 (dd, J ¼ 7.1 and 0.6 Hz, 6H, CH3). 13C NMR d 163.90 (d, J ¼ 3.6 Hz),
137.88, 128.26, 127.35, 127.04, 62.45 (d, J ¼ 6.3 Hz), 43.39, 34.82 (d, J ¼ 131.7 Hz),
15.98 (d, J ¼ 6.4 Hz). Anal. calcd. for C13H20NO4P: C, 54.73; H, 7.07; N, 4.91.
Found: C, 54.70; H, 7.08; N, 4.88.
N,N-Diphenyl diethylphosphonoacetamide (1q). This compound had mp
1
58–60 ꢀC (from ethyl acetate). H NMR d 7.28–7.40 (m, 10H, aromatics), 4.11–4.19
(m, 4H, OCH2), 3.02 (dd, J ¼ 21.7 and 1.4 Hz, 2H, CH2P), 1.29–1.34 (m, 6H,
CH3).13C NMR d 165.18, 142.76, 142.31, 129.84, 128.96, 128.66, 128.13, 126.51,
62.05 (d, J ¼ 5.6 Hz), 34.28 (d, J ¼ 136.8 Hz), 16.31 (d, J ¼ 6.8 Hz). Anal. calcd. for
C18H22NO4P: C, 62.24; H, 6.38; N, 4.03. Found: C, 61.97; H, 6.39; N, 4.01.
ACKNOWLEDGMENTS
This work was supported by the Universidad de Buenos Aires (B-096) and
by CONICET (PIP 11420090100286). We thank Lic. Ignacio L. Berlanga for some
preliminary experiments.
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