A convenient and mild procedure for the preparation of α-keto phosphonates of 1-hydroxyphosphonates under solvent-free conditions using microwave

Article abstract of DOI:10.1081/SCC-100104822

The Reactions of 1-hydroxyphosphonates on the alumina-supported CrO₃ are accelerated by microwave irradiation under solvent-free conditions to afford a high yielding synthesis of α-keto phosphonates.

Full text of DOI:10.1081/SCC-100104822

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A CONVENIENT AND MILD PROCEDURE FOR THE
PREPARATION OF α-KETO PHOSPHONATES OF 1-
HYDROXYPHOSPHONATES UNDER SOLVENT-FREE
CONDITIONS USING MICROWAVE
Babak Kaboudin a & Rahman Nazari a
a Institute for Advanced Studies in Basic Sciences (IASBS), Gava Zang, Zanjan, 45195-159,
Iran
Published online: 09 Nov 2006.
To cite this article: Babak Kaboudin & Rahman Nazari (2001) A CONVENIENT AND MILD PROCEDURE FOR THE PREPARATION
OF α-KETO PHOSPHONATES OF 1-HYDROXYPHOSPHONATES UNDER SOLVENT-FREE CONDITIONS USING MICROWAVE, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry, 31:15, 2245-2250,
DOI: 10.1081/SCC-100104822
To link to this article: http://dx.doi.org/10.1081/SCC-100104822
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SYNTHETIC COMMUNICATIONS, 31(15), 2245–2250 (2001)
A CONVENIENT AND MILD PROCEDURE
FOR THE PREPARATION OF
a-KETO PHOSPHONATES OF
1-HYDROXYPHOSPHONATES UNDER
SOLVENT-FREE CONDITIONS
USING MICROWAVE
Babak Kaboudin* and Rahman Nazari
Institute for Advanced Studies in Basic Sciences (IASBS),
Gava Zang, Zanjan, 45195-159, Iran
ABSTRACT
The Reactions of 1-hydroxyphosphonates on the alumina-
supported CrO3 are accelerated by microwave irradiation
under solvent-free conditions to afford a high yielding syn-
thesis of a-keto phosphonates.
Phosphonic and analogues of naturally occurring phosphates have
attracted considerable interest as potential regulators, mediators, or inhibi-
tions of metabolic processes.1 a-Ketophosphonates have a number of pro-
perties that make them attractive as reagents or intermediates for synthesis.
These properties have stimulated a recent resurgence of interest in the
chemistry of such compounds.2–6 For several years it has been
* Corresponding author.
2245
Copyright & 2001 by Marcel Dekker, Inc.
www.dekker.com

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KABOUDIN AND NAZARI
known that the carbonyl of an a-ketophosphonate is activated towards
attack by nucleophiles and that the carbon-phosphorus bond is readily
cleaved.7 This property makes a-ketophosphonates potentially useful acylat-
ing agents, but also susceptible to hydrolysis and difficult to handle.7 The
chemical properties of a-ketophosphonates are mainly determined by the
phosphorus substituents, but in general are hybrid between those of second-
ary amides and ketones.8 For instance, it is possible to derive hydrazones,
imines, and oximes from the carbonyl function;9 or use them in witting reac-
tions.7a a-Ketophosphonates are usually prepared by a Michaelis-Arbuzov
reaction between a trialkyl phosphite and acid chloride.10 The Michaelis-
Arbuzov reaction works well for the less complex aroyl and alkanoyl chlor-
ides where purification by distillation is possible. However, there has been less
success in the preparation of a,b-unsaturated a-ketophosphonates where
multiple addition products are often observed,11a,b and the products are
thermally or acid sensitive compounds.11c An alternative method for the
preparation of a-ketophosphonates is the oxidation of the corresponding
hydroxyphosphonate.12 Although there have been sporadic reports on the
oxidation of hydroxyphosphoryl compounds, the reactions developed tend
to work well withisolated examples, but are not usually general for arrange
of substrates.
Surface-mediated solid phase reactions are of growing interest13
because of their ease of set up and work-up, mild reaction conditions, rate of
the reaction, selectivity, high yields, lack of solvent and the low cost of
the reactions in comparison with their homogeneous counterparts.
Acceleration of organic reactions by microwave dielectric heating has been
widely exploited. Microwave irradiation in solvent-free conditions has also
shown its utility in organic synthesis. As a part of our efforts to explore the
utility of surface-mediated reactions,14,15,16 in this report a new method for
the preparation of a-ketophosphonates by oxidation of 1-hydroxyphos-
phonates on the solid surface under microwave irradiation is described. It is
found that alumina (neutral)-supported CrO3 under solvent-free conditions
was capable of producing high yields of a-ketophosphonates from 1-hydroxy
phosphonates under mild reaction conditions (Scheme 1, and Table 1).
Scheme 1.

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1-HYDROXYPHOSPHONATES
2247
As shown Table 1, 1-hydroxyalkyl, and a,b-unsaturated phosphonates in the
presence of alumina supported chromium (VI) oxide under
microwave irradiation afford the desired products in excellent yields
(2a–f). The reaction also proceeded in high yields for o-, m- and p-substi-
tuted 1-hydroxyphosphonates in the presence of alumina supported
chromium (VI) oxide under microwave irradiation afford the desired
products in excellent yields (2g–o). The reaction also proceeded in high
yields for 1-hydroxyfurfuryl, a-naphthyl, and b-naphthyl phosphonates
(2p–r).
The reactions are relatively clean with no tar formation, and interest-
ingly, no cleavage of the C-P bond is observed. Indeed a wide range of
1-hydroxyphosphonates was converted to corresponding a-keto phospho-
nates under this condition.
In summary, simple work-up, low consumption of solvent, relatively
fast reaction rates, mild reaction condition, good yields, and selectivity of
the reaction make this method an attractive and a useful contribution to
present methodologies.
Table 1. The Preparation of a-Ketophosphonates of 1-Hydroxyphosphonates (1)
under Solvent-Free Condition Using Microwave Irradiation
Product
2
Time
(min)
Yielda
(%)
R-
n-C4H9
n-C5H11-
PhCH2CH2-
PhCHCH3
Ph-CH¼CH-
Me-CH¼CH-
Ph-
p-CH3C6H4-
p-ClC6H4-
p-O2NC6H4-
p-CH3OC6H4-
o-ClC6H4-
o-NO2C6H4-
2,4-Cl2C6H3-
Furfuryl
a
b
c
d
e
f
g
h
i
2
2
2
3
1
1
0.5
1
1
0.5
1
1
1
2
1
1
1
75
76
78
73
68
73
86
85
85
89
86
80
85
78
75
89
85
j
k
l
m
n
o
p
q
a-Naphthyl
b-Naphthyl
a Isolated yields.

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KABOUDIN AND NAZARI
EXPERIMENTAL SECTION
General
All chemicals were commercial products and distilled or recrystallized
before use. A kitchen type microwave at 2450 MHz (900 W) was used in
all experiments. The infrared (IR) spectra were determined neat using a
1
FTIR. H NMR (at 500 MHz) spectra were obtained as solutions in deu-
teriochloroform (CDCl3).
Preparation of a-Ketophosphonates (2) of 1-Hydroxyphosphonates 1.
This solvent-free oxidation method is operationally simple. Thirty mmol
of the reagent is prepared by the combination of CrO3 (30 mmol, finely
ground) and alumina (Al2O3, neutral, 5.75 g) in a mortar and pestle by
grinding then together until a fine, homogeneous, orange powder is obtained
(5–10 min). The 1-hydroxyphosphonate17 (10 mmol) was added to this
reagent and was irradiated by microwave. The reaction mixture was
washed with CH2Cl2 (200 mL), dried (Na2SO4), and the solvent evaporated
to give the crude products. Pure product was obtained by distillation under
reduced pressure in 65–90% yields.
Acylphosphonates 2. All products gave satisfactory spectral data in
7
accord withthe assigned structures and literature reports.
[E.g. for 2g
1H NMR (CDCl3, TMS) d: 1.22 (t, 3H, J ¼ 6 Hz, -OCH2CH3), 1.23 (t,
3H, J ¼ 6 Hz, -OCH2CH3), 4.05–4.72 (m, 4H, -OCH2CH3), 7.28 (t, 2H,
J ¼ 7.3 Hz), 7.54 (t, 1H, J ¼ 7.3 Hz), 8.18 (d, 2H, J ¼ 7.3 Hz); IR (neat): ꢀ
1659 (C ¼ O), 1610 (Ar), 1258 (P ¼ O), 1103–1025, 978 (P-O-Et) cmꢀ1].
ACKNOWLEDGMENT
The Institute for Advanced Studies in Basic Sciences (IASBS) is
thanked for supporting the work.
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2
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under reduced pressure.
Received in Japan July 6, 2000

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