High yield preparation of α-ketophosphonates by oxidation of α-hydroxyphosphonates with zinc dichromate trihydrate (ZnCr2O7·3H2O) under solvent-free conditions

Article abstract of DOI:10.1016/S0040-4039(01)00712-2

Various types of α-hydroxyphosphonates were converted to α-ketophosphonates by zinc dichromate trihydrate in high yields and rates under solvent-free conditions.

Full text of DOI:10.1016/S0040-4039(01)00712-2

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 4369–4371
High yield preparation of a-ketophosphonates by oxidation of
a-hydroxyphosphonates with zinc dichromate trihydrate
(ZnCr2O7·3H2O) under solvent-free conditions
Habib Firouzabadi,* Nasser Iranpoor,* Sara Sobhani and Ali-Reza Sardarian
Department of Chemistry, College of Sciences, Shiraz University, Shiraz 71454, Iran
Received 25 January 2001; accepted 27 April 2001
Abstract—Various types of a-hydroxyphosphonates were converted to a-ketophosphonates by zinc dichromate trihydrate in high
yields and rates under solvent-free conditions. © 2001 Elsevier Science Ltd. All rights reserved.
a-Ketophosphonates are fascinating and versatile com-
pounds in organic synthesis.1 The chemical properties
of a-ketophosphonates are mainly determined by the
phosphorus substituents, but in general are a hybrid
between ketones and secondary amides.2 For instance,
it is possible to derive hydrazones,3 imines,4 and
oximes5 from the carbonyl function; to reduce a-
On the other hand, in view of economical and environ-
mental demands, simplicity in processes and low costs,
solvent-free reactions in organic synthesis have recently
been receiving interest.12 Along this line, we have
reported new methods for functional group
transformations.13
ketophosphonates
to
the
corresponding
a-
hydroxyphosphonates6 or use them in Wittig reactions.7
The C(O)ꢀP bonds in these compounds are known to
be sensitive towards hydrolysis.8 Therefore, handling
a-ketophosphonates is not so easy and requires special
precautions.8 The Michael–Arbuzov reaction is a gen-
eral method for the preparation of a-ketophosphonates
from acyl chlorides and trialkylphosphites.9 Oxidation
of a-hydroxyphosphonates10 is another reaction for the
preparation of a-ketophosphonates. However, a survey
of the literature indicates that reports of the oxidation
of a-hydroxyphosphonates are rare. Oxidation by
known reagents requires long reaction times, high
molar ratios of the oxidant/substrate or special treat-
ment for the activation of the reagent.11
Table 1. Oxidation of a-hydroxyphosphonates to a-
ketophosphonates by zinc dichromate trihydrate at room
temperature under solvent-free conditions; comparison
11b
with CrO3/Al2O3
11b
Product R-
2
ZnCr2O7·
3H2O
CrO3/Al2O3
Yielda (%) Timeb
(h)
Yieldb
(%)
a
b
c
d
e
f
g
h
i
C6H5-
4-CH3C6H4-
4-CH3OC6H4-
2,4,6-(CH3)3C6H2- 90
2-ClC6H4-
3-ClC6H4-
4-ClC6H4-
2,6-Cl2C6H3-
2-O2NC6H4-
3-O2NC6H4-
4-O2NC6H4-
2-naphthyl
i-C3H7-
95
95
90
4
6
8
–
6
–
4
–
4
3
2.5
4
–
89
85
78
–
75
–
96
95
94
95
95
90
90
91
92
90
–
70
85
85
85
–
j
k
l
Scheme 1.
m
a Isolated yields, oxidant/substrate=1:1, immediate reaction
occurred.
* Corresponding authors. Fax: (711) 2220027; e-mail: firouzabadi@
chem.susc.ac.ir
b Oxidant/substrate=3:1.
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)00712-2

4370
H. Firouzabadi et al. / Tetrahedron Letters 42 (2001) 4369–4371
Herein we report that zinc dichromate trihydrate14 is an
efficient reagent for the preparation of a-ketophospho-
nates by oxidation of a-hydroxyphosphonates at room
temperature under solvent-free conditions (Scheme 1).
We have compared our results with those reported for
CrO3/Al2O3 (Table 1).11b
7. Yamashita, M.; Kojima, M.; Yoshida, H.; Ogata, T.;
Inokawa, S. Bull. Chem. Soc. Jpn. 1980, 53, 1625.
8. (a) Ackerman, B.; Jordan, T. A.; Eddy, C. R.; Swen,
D. J. Am. Chem. Soc. 1956, 78, 4444; (b) Kluger, R.;
Pick, D. C.; Chin, J. Can. J. Chem. 1978, 56, 1792; (c)
Jugelt, W.; Andreae, S.; Schubert, G. J. Prackt. Chem.
1971, 83.
9. (a) Berlin, K. D.; Hellwege, D. M.; Nagabhushanam,
M. J. Org. Chem. 1965, 1265; (b) Berlin, K. D.; Taylor,
H. A. J. Am. Chem. Soc. 1964, 86, 3862.
10. (a) Texier-Boullet, F.; Foucaud, A. Synthesis 1982, 916;
(b) Baraldi, P. G.; Guarneri, M.; Moroder, F.; Polloni,
G. P.; Simoni, D. Synthesis 1982, 11, 653; (c) Sardar-
ian, A. R.; Kaboudin, B. Synth. Commun. 1997, 27,
543.
As shown in Table 1, in the presence of zinc dichromate
trihydrate, various (a-hydroxyphenylmethyl) phospho-
nates (1a–k) were cleanly converted into the corre-
sponding a-ketophosphonates (2a–k) in excellent yields
(90–96%). a-Hydroxy-2-naphthyl and alkyl phospho-
nates (1l,m) were also oxidized efficiently giving the
corresponding a-ketophosphonates (2l,m) in 91–92%
yields.
11. (a) Smyth, M. S.; Ford, Jr., H.; Burke, Jr., T. R. Tet-
rahedron Lett. 1992, 33, 4137; (b) Kaboudin, B. Tetra-
hedron Lett. 2000, 41, 3169; (c) Liao, Y.; Shabany, H.;
Christopher, D. S. Tetrahedron Lett. 1998, 39, 8389.
12. Tanaka, K.; Toda, F. Chem. Rev. 2000, 100, 1025 and
references cited therein.
13. (a) Firouzabadi, H.; Karimi, B.; Abbassi, M. J. Chem.
Res. (S) 1999, 236; (b) Firouzabadi, H.; Iranpoor, N.;
Zolfigol, M. A. Synth. Commun. 1998, 28, 1179.
14. Firouzabadi, H.; Sardarian, A. R.; Moosavipoor, H.;
Afshari, G. M. Synthesis 1986, 285.
Comparison of the results in the presence of zinc
dichromate trihydrate with those reported by CrO3/
Al2O3 indicated that: (1) the yields are higher; (2) the
reaction occurs immediately; (3) the support for the
oxidation was not required,15 and (4) the ratio of the
oxidant used was less.16,17
In conclusion, mild reaction conditions, high reaction
rates, high yields, solventless conditions deserve to be
mentioned for the present procedure and make it a
useful method for the preparation of various a-
ketophosphonates without requiring a large amount of
the oxidant.
15. In our laboratory, we tried similar oxidations with
unsupported CrO3. The results showed that this reagent
was sluggish for this aim and a messy reaction mixture
was obtained.
16. Typical procedure for the preparation of h-ketophospho-
nates from 1-hydroxyphosphonates: A mixture of the a-
hydroxyphosphonate 1 (5 mmol) and zinc dichromate
trihydrate14 (5 mmol) was ground together in a mortar
with a pestle. The reaction occurred immediately and
the mixture was washed with carbon tetrachloride (4×
15 ml) and dried over anhydrous Na2SO4. The solvent
was evaporated to give the desired crude product. The
pure product(s) were obtained by vacuum distillation in
90–96% yields (Table 1).
Acknowledgements
We thank Shiraz University Research Council and
National Research Council of I.R. Iran for grant
no.464 for the partial support of this work.
References
17. Spectral data of some a-ketophosphonates: 2a [1H
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2-OCH2CH3), 4.08–4.28 (dq, 4H, JPOCH=7.1 Hz, JHH
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7 Hz, 2-OCH2CH3), 7.28–7.6 (m, 3H), 8.03–8.25 (m,
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MS: M+ (242)]. 2b [1H NMR (CDCl3, TMS): l 1.29–
1.42 (t, 6H, JHH=7 Hz, 2-OCH2CH3), 2.35 (s, 3H,
-CH3), 4.11–4.16 (dq, 4H, JPOCH=7.1 Hz, JHH=7 Hz,
2-OCH2CH3), 7.12–7.21 (m, 2H), 8.04–8.07 (m, 2H)
ppm; IR (neat): w 1650 (CꢁO), 1260 (PꢁO) cm−1; MS:
M+ (256)]. 2c [1H NMR (CDCl3, TMS): l 1.11–1.29 (t,
6H, JHH=7 Hz, 2-OCH2CH3), 3.80 (s, 3H, -CH3),
3.90–4.10 (dq, 4H,
JPOCH=7.1 Hz, JHH=7 Hz, 2-
OCH2CH3), 6.84–6.90 (m, 2H), 7.42–7.50 (m, 2H) ppm;
IR (neat): w 1650 (CꢁO), 1265 (PꢁO) cm−1; MS: M+
(272)]. 2d [1H NMR (CDCl3, TMS): l 1.25–1.32 (t, 6H,
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2.27 (s, 3H, 4-Me), 4.06–4.17 (dq, 4H, JPOCH=7.1 Hz,
J
HH=7 Hz, 2-OCH2CH3), 6.83 (s, 2H) ppm; IR (neat):
w 1660 (CꢁO), 1250 (PꢁO) cm−1; MS: M+ (284)]. 2g [1H
NMR (CDCl3, TMS): l 1.13–1.42 (t, 6H, JHH=7 Hz,
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2-OCH2CH3), 4.15–4.33 (dq, 4H, JPOCH=7.1 Hz, JHH
7 Hz, 2-OCH2CH3), 7.47–7.50 (m, 2H), 8.21–8.24 (m,
2H) ppm; IR (neat): w 1660 (CꢁO), 1260 (PꢁO) cm−1
=
;

H. Firouzabadi et al. / Tetrahedron Letters 42 (2001) 4369–4371
4371
MS: M+ (277), M++2 (279)]. 2h [1H NMR (CDCl3,
TMS): l 1.04–1.24 (t, 6H, JHH=7 Hz, 2-OCH2CH3),
1.19–1.27 (t, 6H, JHH=7 Hz, 2-OCH2CH3), 4.08–4.18
(dq, 4H, JPOCH=7.1 Hz, JHH=7 Hz, 2-OCH2CH3),
7.42–7.47 (m, 1H), 7.64–7.70 (m, 1H), 7.94–8.01 (m, 2H)
ppm; IR (neat): w 1650 (CꢁO), 1250 (PꢁO) cm−1; MS: M+
(287)].
3.95–4.23 (dq, 4H,
JPOCH=7.1 Hz, JHH=7 Hz, 2-
OCH2CH3), 6.90–7.09 (m, 3H) ppm; IR (neat): w 1690
(CꢁO), 1260 (PꢁO) cm−1]. 2i [1H NMR (CDCl3, TMS): l
.