An efficient microwave-promoted solvent-free α-phosphoryloxylation of ketones

Article abstract of DOI:10.2174/157017812802139717

An efficient solvent-free α-phosphoryloxylation of ketones under microwave irradiation is reported. When ketones reacted with phosphates and (diacetoxyiodo)benzene under microwave irradiation for short time, the α-phosphoryloxylaction of ketones was easil

Full text of DOI:10.2174/157017812802139717

522
Letters in Organic Chemistry, 2012, 9, 522-525
An Efficient Microwave-Promoted Solvent-Free ꢀ-Phosphoryloxylation of
Ketones
Ye Pua, Yingguo Fangb and Jie Yan a,*
aCollege of Chemical Engineering and Materials Sciences, Zhejiang University of Technology, Hangzhou 310032, Zhe-
jiang, P. R. China
bCollege of Biological and Environmental Sciences, Zhejiang Shuren University, Hangzhou 310015, P. R. China
Received February 17, 2012: Revised April 07, 2012: Accepted April 10, 2012
Abstract: An efficient solvent-free ꢀ-phosphoryloxylation of ketones under microwave irradiation is reported. When ke-
tones reacted with phosphates and (diacetoxyiodo)benzene under microwave irradiation for short time, the ꢀ-
phosphoryloxylaction of ketones was easily be carried out and the corresponding ketol phosphates were prepared in mod-
erate to good yields.
Keywords: ꢀ-Phosphoryloxylation, (Diacetoxyiodo)benzene, ketol phosphate, ketone, microwave irradiation, synthesis.
INTRODUCTION
have checked the reaction of ketones with (diacetoxy-
iodo)benzene (DIB) and phosphates under microwave irra-
diation in the absence of solvents, a good result for the direct
ꢀ-phosphoryloxylation of ketones has been obtained. Now
we wish to report here a rapid and efficient microwave-
assisted ꢀ-phosphoryloxylation of ketones without solvents.
Organic hypervalent iodine reagents have found broad
application in organic chemistry and frequently used in syn-
thesis due to their chemical properties and reactivity is simi-
lar to those of Hg (II), Tl (III) and Pb (IV), but without the
toxic and environmental problems of these heavy metal con-
geners [1]. Among these hypervalent iodine reagents, [hy-
droxy(tosyloxy)iodo]benzene (Koser’s reagent) is the most
popular and useful reagent for the direct ꢀ-tosyloxylation of
ketones, and the prepared ꢀ-tosyloxyketones are important
strategic precursors for the construction of various het-
eroaromatics [2]. However, the analog reaction for the
preparation of the important ketol phosphates by the direct
ꢀ-phosphoryloxylation of ketones with hypervalent iodine
reagents has been rather limited [3]. Due to many hyperva-
lent iodine reagents have low solubility in most organic sol-
vents and in order to extend the scope of ꢀ-phosphoryloxy-
lation of ketones as well as to prepare more ketol phos-
phates, the development of solvent-free reactions and other
special reactions is a big step forward and should lead to an
increasing use of this chemistry.
At the beginning, acetophenone was mixed with equal
equiv of diphenyl phosphate and DIB to examine the ꢀ-
phosphoryloxylation. It was found that the mixture was
heated in a glass tube by a microwave irradiation at full
power (650 W) for 50 seconds, the reaction provided the
desired product of ꢀ-phosphoryloxyacetophenone in 45%
isolated yield. Then, a series of experiments was performed
on the reaction of acetophenone with DIB and diphenyl
phosphate in order to determine the optimum reaction condi-
tions. It was found that when more acetophenone was used
in the reaction, the yield was increased; and when 2 equiv of
acetophenone reacted with 1 equiv of diphenyl phosphate
and DIB, the reaction gave the highest yield of 74% after 60
seconds microwave irradiation. However, when 3 equiv of
acetophenone was added to the reaction, the yield was de-
creased to 65%. The influence of the reaction time was also
evaluated and 60 seconds was the best choice. When the
mixture of 2 equiv of acetophenone and 1 equiv of diphenyl
phosphate and DIB was heated longer than 70 seconds, the
product was found to be decomposed partly. So, according to
our investigation, the optimal ratio of acetophenone to
diphenyl phosphate and DIB was 2:1:1, and the optimal time
for microwave irradiation was 60 seconds. Under the opti-
mum reaction conditions, the ꢀ-phosphoryloxylation of ke-
tones (1) with phosphates (2) and DIB was investigated
(Scheme 1), the good results are summarized in Table 1.
Microwave-promoted organic syntheses have received
great attention because of their fast reaction rates, high pu-
rity of products, and ease of manipulation [4]. In particular,
the microwave-irradiated procedures in water medium or in
the absence of solvents for organic synthesis have attracted
considerable interest in recent years due to their efficient and
environmentally benign conditions [5]. Our recent interest
has been in the development of new synthetic methods using
hypervalent iodine compounds and as part of a program, we
From Table 1, it is notable that except 1d (entry 4), all
ketones reacted with phosphates and DIB easily under mi-
crowave irradiation and gave the corresponding ketol phos-
phates in moderate to good yields. Ketone with electron-
*Address correspondence to these author at the College of Chemical Engi-
neering and Materials Sciences, Zhejiang University of Technology,
Hangzhou 310032, P. R. China; Tel: +86 (571) 88320163; Fax: +86 (571)
88320238; E-mail: jieyan87@zjut.edu.cn
1875-6255/12 $58.00+.00
© 2012 Bentham Science Publishers

Microwave-Promoted ꢀ-Phosphoryloxylation of Ketones
Letters in Organic Chemistry, 2012, Vol. 9, No. 7
523
O
O
O
microwave
RCCH2R' + PhI(OAc)2 + (R''O)2PO2H
RCCH(R')OP(OR'')2
1
3
2
3a: R=Ph, R'=H, R''=Ph
3b: R=Me, R'=H, R''=Ph
3c: R=p-NO2-C6H4, R'=H, R''=Ph
1a: R=Ph, R'=H
1b: R=Me, R'=H
1c: R=p-NO2-C6H4, R'=H
2a: R''=Ph
2b: R''=Bz
3d: R=p-Me-C6H4, R'=H, R''=Ph
1d: R=p-Me-C6H4, R'=H
1e: R=Ph, R'=COMe
1f: R=Ph, R'=Me
3e: R=Ph, R'=COMe, R''=Ph
3f: R=Ph, R'=Me, R''=Ph
3g: R=Ph, R'=H, R''=Bz
3h: R=Me, R'=H, R''=Bz
Scheme 1.
Table 1. The Result of the ꢁ-Phosphoryloxylation of Ketone
Entry
Ketone (1)
Phosphate (2)
Ketol Phosphate (3)
Time (s)
Yield (%)a
1
2
3
4
5
6
7
1a
1b
1c
1d
1e
1f
2a
2a
2a
2a
2a
2a
2b
2b
3a
3b
3c
3d
3e
3f
60
60
60
60
50
60
60
60
74
61
64
45
81
52
65
61
1a
1b
3g
3h
8
a Isolated yield
withdrawing substituent group in phenyl (1c) got product in
higher yield than that with electron-donating substituent
group in phenyl (1d) (entries 3-4). When ꢀ-diketone (1e)
was used in the reaction, it usually needed shorter time and
obtained better yield (entry 5). Due to the hinder effect of
methyl group, propionylbenzene (1f) provided the corre-
sponding product in somewhat lower yield compared with
acetophenone (entry 6). Another phosphate 2b was effective
as 2a in the reaction and resulted in the corresponding ketol
phosphates in moderate yields (entries 7-8).
(diacetoxyiodo)benzene and phosphates were commercially
available.
The ꢁ-phosphoryloxylation of Ketone General Procedure
Acetophenone (1a) (120.2 mg, 1.0 mmol, 2.0 equiv) was
mixed with diphenyl phosphate (2a) (125.1 mg, 0.5 mmol,
1.0 equiv) and (diacetoxyiodo)benzene (161.0 mg, 0.5mmol,
1.0 equiv) in a 10 mL glass tube. The mixture tube was
placed inside an alumina bath and irradiated for 60 seconds
in a microwave reactor at full power (650 W). After cooling,
water (5 mL) was added. The mixture was extracted with
CH2Cl2 (2ꢀ5 mL) and the combined organic layer was
washed with brine, dried over anhydrous MgSO4, filtered
and concentrated under reduced pressure to give the residue.
The residue was purified on a silica gel plate using (4:1 hex-
ane-ethyl acetate) as eluant to give 136.2 mg of ꢁ-
phosphoryloxyacetophenone (3a) (74% yield).
In summary, a rapid and efficient method for direct ꢁ-
phosphoryloxylation of ketones is afforded by the micro-
wave-promoted solvent-free reaction. It is simple, fast and
affords ketol phosphates in moderate to good yields. Fur-
thermore, the useful range of hypervalent iodine compounds
in organic syntheses has been extended.
EXPERIMENTAL
ꢁ-(Diphenylphosphoryloxy)acetophenone (3a) 3a
1
IR spectra were recorded on a Thermo-Nicolet 6700 in-
strument, NMR spectra were measured on a Bruker
ANANCE ꢀ (500MHz) spectrometer, and Mass spectra
were determined on Thermo-ITQ 1100 mass spectrometer.
Microwave irradiation was carried out with a LWMC-201
microwave reactor at full power (650 W) (Nanjing, China).
Wakogel B-5F was selected for preparing TLC. Ketones,
Oil; H NMR (500 MHz, CDCl3): 7.89ꢂ7.87 (m, 2H),
7.62ꢂ7.59 (m, 1H), 7.49ꢂ7.46 (m, 2H), 7.37ꢂ7.34 (m, 4H),
7.30ꢂ7.26 (m, 4H), 7.22ꢂ7.19 (m, 2H), 5.46 (d, J =10.0 Hz,
2H); 13C NMR (125 MHz, CDCl3): 191.20 (d, J =5.0 Hz),
150.40 (d, J =7.5 Hz), 134.04, 133.72, 129.78, 128.88,
127.78, 125.51, 120.18 (d, J =5.0 Hz), 69.90 (d, J =5.0 Hz);
IR (film, cm-1): 1709, 1291; MS (EI, m/z, %): 369 (M+1,

524 Letters in Organic Chemistry, 2012, Vol. 9, No. 7
Pu et al.
3.5), 275 (100); HRMS: C20H17O5P calcd.: 368.0809, found:
368.0782.
ꢀ-(Dibenzylphosphoryloxy)acetophenone (3g) 3d
1
Oil; H NMR (500 MHz, CDCl3): 7.84 (d, J = 8.0 Hz,
2H), 7.58-7.52 (m, 1H), 7.47 (d, J = 8.0Hz, 2H), 7.34-7.30
(m, 10H), 5.22 (d, J = 10.0 Hz, 2H), 5.18 (dd, J = 8.0, 6.0
Hz, 4H); 13C NMR (125 MHz, CDCl3): 191.99 (d, J = 5.0
Hz), 135.67 (d, J = 6.3 Hz), 133.89, 128.80, 128.51, 128.02,
127.68, 69.70 (d, J = 5.0 Hz), 68.67 (d, J = 5.0 Hz); IR
(film, cm-1): 1708, 1279; MS (EI, m/z, %): 397 (M+, 1.8),
199 (100); HRMS: C22H21O5P calcd.: 396.1127, found:
396.1121.
ꢀ-(Diphenylphosphoryloxy)acetone (3b) 3a
1
Oil; H NMR (500 MHz, CDCl3): 7.38ꢁ7.34 (m, 4H),
7.28ꢁ7.26 (m, 2H), 7.23ꢁ7.22 (m, 4H), 4.72 (d, J =9.5 Hz,
2H), 2.16 (s, 3H); 13C NMR (125 MHz, CDCl3): 201.39 (d, J
=6.3 Hz), 150.17 (d, J = 6.3 Hz), 129.72, 125.50, 119.94 (d,
J = 5.0 Hz), 71.54 (d, J = 6.3 Hz), 25.78; IR (film, cm-1):
1739, 1290, 1194; MS (EI, m/z, %): 307 (M+1, 2.0), 250
(100); HRMS: C15H15O5P calcd.: 306.0657, found:
306.0624.
ꢀ-(Dibenzylphosphoryloxy)acetone (3h)
1
Oil; H NMR (500 MHz, CDCl3): 7.38-7.36 (m, 10H),
ꢀ-(Diphenylphosphoryloxy)-4-nitroacetophenone (3c) 3d
5.12 (dd, J = 18.0, 9.0 Hz, 4H), 4.45 (d, J = 9.5 Hz, 2H),
2.12 (s, 3H); 13C NMR (125 MHz, CDCl3): 202.29 (d, J =
6.3 Hz), 135.51 (d, J = 7.5 Hz), 134.44, 128.62 (d, J = 7.5
Hz), 128.03, 70.66 (d, J = 6.3 Hz) 69.75 (d, J = 6.3
Hz),25.85; IR (film, cm-1): 1740, 1280; MS (EI, m/z, %): 335
(M+1, 6.0), 137 (100); HRMS: C17H19O5P calcd.: 334.0970,
found: 334.0934.
1
Oil; H NMR (500 MHz, CDCl3): 8.31 (d, J = 9.0 Hz,
2H), 8.04 (d, J = 9.0 Hz, 2H), 7.36 (d, J = 7.5 Hz, 4H),
7.29ꢁ7.23 (m, 6H), 5.45 (d, J = 10.5 Hz, 2H); 13C NMR
(125 MHz, CDCl3): 190.53 (d, J = 5.0 Hz), 150.78, 150.28
(d, J = 7.5 Hz), 138.19, 129.88, 129.10, 125.74, 124.05,
120.14 (d, J = 5.0 Hz), 70.02 (d, J = 5.0 Hz); IR (film, cm-
1): 1693, 1527, 1346, 1261; MS (EI, m/z, %): 413 (M+, 1.9),
94 (100); HRMS: C20H16NO7P calcd.: 413.0664, found:
413.0632.
ACKNOWLEDGEMENTS
Financial support from the Natural Science Foundation
of China (Project 21072176) and the Zhejiang Province
Natural Science Foundation of China (Project Y4100231)
are greatly appreciated.
ꢀ-(Diphenylphosphoryloxy)-4-methylacetophenone (3d)
1
Oil; H NMR (500 MHz, CDCl3): 7.79 (d, J =8.0 Hz,
2H), 7.38-7.35 (m, 4H), 7.32-7.27 (m, 6H), 7.23-7.18 (m,
2H), 5.45 (d, J =10.0 Hz, 2H); 13C NMR (125 MHz, CDCl3):
190.79, 150.49 (d, J =7.5 Hz), 145.12, 131.31, 129.81,
129.61, 128.46, 125.52, 120.20 (d, J =7.5 Hz), 69.88 (d, J
=6.3 Hz), 21.76; IR (film, cm-1): 1700, 1288; MS (EI, m/z,
%): 383 (M+1, 2.9), 289 (100); HRMS: C21H19O5P calcd.:
382.0970, found: 382.0953; HRMS: C21H19O5P calcd.:
382.0970, found: 382.0953.
CONFLICT OF INTEREST
Declared none.
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