Environmentally Friendly and Efficient Process for the Preparation of β-Hydroxyl Ketones

Article abstract of DOI:10.1021/op0341263

An environmentally benign and efficient process for the preparation of β-hydroxyl ketones was developed by the practical cross-aldol reactions of 2-acetylpyridine, acetophenone, and cyclohexanone with 4-nitro-, 3-nitro-, and 2-nitrobenzaldehydes in water

Full text of DOI:10.1021/op0341263

Organic Process Research & Development 2004, 8, 18−21
Articles
Environmentally Friendly and Efficient Process for the Preparation of
â-Hydroxyl Ketones
Guan-Wu Wang,* Ze Zhang, and Ya-Wei Dong
Department of Chemistry, UniVersity of Science and Technology of China, Hefei, Anhui 230026, P.R. China
Abstract:
bases7 have been explored as alternative catalysts, but in most
cases the ketones need to be modified as silyl enol ethers,
ketene silyl acetals, etc.
An environmentally benign and efficient process for the
preparation of â-hydroxyl ketones was developed by the
practical cross-aldol reactions of 2-acetylpyridine, acetophenone,
and cyclohexanone with 4-nitro-, 3-nitro-, and 2-nitrobenzal-
dehydes in water catalyzed by Na2CO3 in very high yields.
The K2CO3-induced intramolecular aldol reaction in CH3-
OH/H2O was reported to give a mixture of R,â-unsaturated
ketones resulting from the dehydration of the initially formed
â-hydroxyl ketones.8 Alkali and earth alkali metal salts
including Na2CO3 have also been used to promote aldol
reaction of dimethylsilyl enolates in aqueous dimethylfor-
mamide.9 However, a certain amount of diol was formed by
the tandem aldol-reduction reaction in the case of Na2CO3.
Aldol reactions in pure water have been reported; however,
the substrates have to be modified as silyl enol ethers, ketene
silyl acetals, and boron enolates.10 Most recently, proline-
catalyzed aldol reactions in aqueous micelles has been
reported.11 To the best of our knowledge, there is no report
of aldol reaction in pure water promoted by Na2CO3 at
ambient temperature. Herein we present the highly efficient
and practical aldol reaction of unmodified ketones with
reactive aldehydes bearing strong electron-withdrawing
groups in water catalyzed by Na2CO3 at room temperature.
Introduction
Environmentally friendly chemical process is the vital part
of the current chemical research and development.1 Organic
reactions in water2 have attracted more and more attention
from chemists because there are many potential advantages
and benefits in terms of cost, safety, environmental concerns,
efficiency, and selectivity when the common organic solvents
are replaced by water in organic reactions.3
The aldol reaction is one of the most powerful and useful
reactions utilized in the construction of the carbon-carbon
bond.4 Aldol reaction has been classically conducted in the
presence of strong base or acid.5 However, under such strong
basic or acidic condition, the synthesis of the desired aldol
product is plagued by the concomitant R,â-unsaturated
ketone, formed through aldol dehydration,5a,c and other side
products from polycondensation, self-condensation of the
ketone, Michael addition to the formed enone, and so on.5a
To overcome these problems, various Lewis acids6 or Lewis
Results and Discussion
Recently we have reported the efficient synthesis of chal-
cone and azachalcone by the aldol reactions of ketones with
various aldehydes catalyzed by Na2CO3 at elevated temper-
atures.12 When the reactions were conducted at ambient tem-
perature, a mixture of â-hydroxyl ketones and the dehydra-
tion products, that is, chalcones and azachalcones, was ob-
tained in most cases. However, we found that the reactions
* To whom correspondence should be addressed. E-mail: gwang@ustc.edu.cn.
(1) Anastas, P. T.; Warner, J. C. Green Chemistry: Theory and Practice;
Oxford, 1998.
(2) (a) Li, C.-J.; Chan, T.-H. Organic Reactions in Aqueous Media; John Wiley
& Sons: New York, 1997. (b) Organic Synthesis in Water; Grieco, P. A.,
Ed.; Blackie Academic and Professional: London, 1998. (c) Lubineau, A.;
Auge´, J. Top. Curr. Chem. 1999, 206, 1-59.
(7) For recent examples, see: (a) Denmark, S. E.; Stavenger, R. A.; Wong,
K.-T.; Su, X. J. Am. Chem. Soc. 1999, 121, 4982-4991. (b) Sakthivel, K.;
Notz, W.; Bui, T.; Barbas, C. F., III. J. Am. Chem. Soc. 2001, 123, 5260-
5267.
(3) Lindstro¨m, U. M. Chem. ReV. 2002, 102, 2751-2772.
(4) Healthcock, C. H. In ComprehensiVe Organic Synthesis; Trost, B. M.,
Fleming, I., Eds.; Pergamon Press: Oxford, 1991; Vol. 2, pp 133-238.
(5) (a) For an early work on aldol reactions under strong basic conditions, see:
House, H. O.; Crumrine, D. S.; Teranishi, A. Y.; Olmstead, H. D. J. Am.
Chem. Soc. 1973, 95, 3310-3324. (b) For a work on intramolecular aldol
reaction in the THF/H2O systems under strong basic and acidic conditions,
see: Denmark, S. E.; Lee, W. Tetrahedron Lett. 1992, 33, 7729-7732. (c)
For a work on NaOH-activated aldol reaction affording a mixture of initially
produced ketol and the dehydrated product, see: Fringuelli, F.; Pani, G.;
Piermatti, O.; Pizzo, F. Tetrahedron 1994, 39, 11499-11508. (d) For a
work on solvent-free aldol reaction attaining chalcone by grinding with
NaOH, see: Raston, C. L.; Scott, J. L. Green Chem. 2000, 2, 49-51.
(6) (a) Mukaiyama, T.; Banno, K.; Narasaka, K. J. Am. Chem. Soc. 1974, 96,
7503-7509. (b) Kobayashi, S.; Manabe, K. Acc. Chem. Res. 2002, 35, 209-
217.
(8) Gil, M. V.; Roma´n, E.; Serrano, J. A. Tetrahedron Lett. 2001, 41, 4625-
4628.
(9) Miura, K.; Nakagawa, T.; Hosomi, A. J. Am. Chem. Soc. 2002, 124, 536-
537.
(10) For some examples, see: (a) Lubineau, A.; Meyer, E. Tetrahedron 1988,
44, 6065-6070. (b) Manabe, K.; Kobayashi, S. Synlett 1999, 547-548.
(c) Tian, H.-Y.; Chen, Y.-J.; Wang, D.; Zeng, C.-C.; Li, C.-J. Tetrahedron
Lett. 2000, 41, 2529-2532. (d) Manabe, K.; Mori, Y.; Wakabayashi, T.;
Nagayama, S.; Kobayashi, S. J. Am. Chem. Soc. 2000, 122, 7202-7207.
(e) Loh, T.-P.; Feng, L.-C.; Wei, L.-L. Tetrahedron 2000, 56, 7309-7312.
(f) Mori, Y.; Manabe, K.; Kobayashi, S. Angew. Chem., Int. Ed. 2001, 40,
2816-2818.
(11) Peng, Y.-Y.; Ding, Q.-P.; Li, Z.-C.; Wang, P. G.; Cheng, J.-P. Tetrahedron
Lett. 2003, 44, 3871-3875.
(12) Zhang, Z.; Dong, Y.-W.; Wang, G.-W. Chem. Lett. 2003, 32, 966-967.
18
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Vol. 8, No. 1, 2004 / Organic Process Research & Development
10.1021/op0341263 CCC: $27.50 © 2004 American Chemical Society
Published on Web 11/20/2003

Scheme 1. Cross-aldol reactions of ketones 1a-c and
aldehydes 2a-c in water catalyzed by Na2CO3
Table 1. Reaction times, yields and purities for the
cross-aldol reactions of ketones 1a-c with
nitrobenzaldehydes 2a-c in water in the presence of 0.017
mol/L of Na2CO3
Figure 1. Yields of cross-aldol reactions between ketone 1a
and aldehyde 2b in reused aqueous phase.
connecting hydroxy group.10a,13 It is interesting to observe
that the methine group bearing hydroxy group of 3ac, 3bc,
and 3cc downfield shifted about 0.5 ppm in the H NMR
reaction
time (h)
yield (%)a/
purity (%)b
1
entry
ketone
aldehyde
product
spectra and upfield shifted about 4 ppm in the 13C NMR
spectra compared to that of the corresponding 3aa/3ab, 3ba/
3bb, and 3ca/3cb, reflecting the strong influence of the ortho
nitro group of the benzene ring on the chemical shifts of
neighboring methine group in both 1H and 13C NMR spectra.
Besides nitrobenzaldehydes, other reactive aldehydes
bearing strong electron-withdrawing groups could undergo
Na2CO3-catalyzed aldol reactions at room temperature and
give selectively the â-hydroxyl ketones. For example, 3,4-
dichlorobenzaldehyde reacted with 2-acetylpyridine in the
presence of 0.017 mol/L of Na2CO3 in water at ambient
temperature for 9 h to produce 3-(3,4-dichlorophenyl)-3-
hydroxy-1-(2-pyridyl)-1-propanone in 98% yield.
1
2
3
4
5
6
7
8
9
1a
1a
1a
1b
1b
1b
1c
1c
1c
2a
2b
2c
2a
2b
2c
2a
2b
2c
1
2
18
3
10
24
8
26
45
3aa
3ab
3ac
3ba
3bb
3bc
3ca
3cb
3cc
98 (>99)
98 (>99)
87 (>98)
95 (>99)
94 (>99)
92 (>98)
94c (>99)
96d (>99)
87e (>98)
a Isolated yield. b Determined by 1H NMR. c threo:erythro ) 5:1. d threo:
erythro ) 1:1. e threo:erythro ) 2:1.
of 2-acetylpyridine (1a), acetophenone (1b), and cyclohexan-
one (1c) with 4-nitro- (2a), 3-nitro- (2b), and 2-nitrobenzal-
dehyde (2c) could proceed very well under the same condi-
tions to afford cross-aldol products 3 in very high yields
(Scheme 1).
The role of Na2CO3 is a catalyst, and one molar equivalent
of Na2CO3 was not necessary for the aldol reaction. In fact,
a concentration of 0.017 mol/L of Na2CO3 (25% mol equiv)
was enough for the reaction to proceed with completion. The
reaction times, yields, and purities for the cross-aldol reac-
tions of ketones 1a-c (1.05 mmol) with nitrobenzaldehydes
2a-c (1 mmol) in 15 mL of water catalyzed by 0.017 mol/L
of Na2CO3 are listed in Table 1.
From Table 1, it can be seen that the isolated yields are
nearly quantitative with very high purity under the given
reaction conditions. The reactivity orders for the ketones and
aldehydes are 1a > 1b > 1c and 2a > 2b > 2c, respectively.
The lower reactivity of 2-nitrobenzaldehyde relative to that
of 3-nitro- and 4-nitrobenzaldehyde is probably due to the
steric effect of the ortho nitro group. The identities of all
aldol products were unequivocally ascertained by 1H NMR,
13C NMR, HRMS, and FT-IR spectra. In the 1H NMR spectra
of the â-hydroxyl ketones from 2-acetylpyridine and ac-
etophenone, the two methylene protons are magnetically
nonequivalent due to the neighboring chiral methine group,
and each proton has a double-doublet splitting pattern, the
methine proton shows a double-triplet splitting, and the
hydroxy proton is a doublet, fully consistent with their
structures. There are two diastereoisomers for the aldol
products of cyclohexanone and nitrobenzaldehydes, and the
threo/erythro ratios for 3ca, 3cb, and 3cc were determined
by the 1H NMR integrals of the proton of the methine group
Despite the extremely low solubility of both ketones and
aldehydes used in water, the Na2CO3-catalyzed aldol reac-
tions could still proceed efficiently at ambient temperature.
The aldol reaction might take place at the interface of organic
reactants with water in the heterogeneous system. The
sparsely dissolved ketone and aldehyde in water could also
react to give the aldol product in the presence of Na2CO3. It
was found that vigorous stirring was required for the success
of the aldol reaction. The aldol products 3 could be obtained
in practical pure form by simple Bu¨chner filtration of the
final water suspension mixture. The purities of the aldol
products were higher than 98%, as determined by 1H NMR
1
spectroscopy. On the basis of the H NMR measurement,
the ethyl acetate extract of the aqueous filtrate was the
slightly excess unreacted ketone along with trace of the aldol
product in a ratio of ∼50:1. It should be noted that the
aqueous filtrate could be reused for the next batch reaction.
As an example, the reaction of 1a with 2b afforded aldol
3ab quantitatively in all four subsequent runs (Figure 1). In
fact, there was a slight increase of the yield in the subsequent
runs, probably due to the accumulation of the excess
unreacted ketone in the aqueous filtrate. The purity of aldol
3ab was still over 99% in the fifth run.
The use of Na2CO3 in the aldol reaction is superior to
NaOH for the preparation of â-hydroxyl ketones because
byproducts are obtained in the latter case. For example, the
reaction of 1a with 2b in the presence of 0.017 mol/L of
NaOH afforded 54% of 3ab and 38% of dehydration product
(13) Stiles, M.; Winkler, R. R.; Chang, Y.-L.; Traynor, L. J. Am. Chem. Soc.
1964, 86, 3337-3342.
Vol. 8, No. 1, 2004 / Organic Process Research & Development
•
19

3-(3-nitrophenyl)-1-(2-pyridyl)-2-propen-1-one. K2CO3 can
also be used as catalyst in the above aldol reaction and
behaves similarly to Na2CO3.
BRUKER AV400 (100 MHz) spectrometer with complete
proton decoupling, chemical shifts are reported in parts per
million relative to the solvent resonance as the internal
standard (CDCl3, δ 77.16 ppm). High-resolution mass spectra
(HRMS) were recorded on a BRUKER VPEXII spectrometer
with positive CI mode. Analytical TLC and column chro-
matography were performed on silica gel GF254, and silica
gel H60, respectively.
The aldol synthetic method reported here does not require
the preformed silyl enol ethers or ketene silyl acetals which
generate significant amount of metal salts as waste and
usually demand the use of potentially polluting solvents and
low temperatures. Catalyzed reactions of acetophenone and
cyclohexanone with aromatic aldehydes are known to give
chalcones and R,R′-bis(substituted)benzylidenecyclohexanones
under nonaqueous solution14 or solvent-free conditions.14e,15
Under our reaction conditions, no traces of dehydration
products from the initially formed â-hydroxyl ketones 3aa-
cc, self-condensation products of ketones 1a-c, and diols
resulting from the tandem aldol-reduction reactions by Na2-
CO3 were identified for the reactions of ketones 1a-c and
nitrobenzaldehydes 2a-c. â-Hydroxyl ketones 3aa-cc were
the single isolated products with nearly quantitative yields.
Representative Procedure for the Preparation of
â-Hydroxyl ketones 3, 3-(4-Nitrophenyl)-3-hydroxy-1-(2-
pyridyl)-1-propanone (3aa). A mixture of 1a (128 mg, 1.05
mmol) and 2a (151 mg, 1 mmol) in 10 mL of water was
stirred vigorously at room temperature for several minutes
to form enough turbidity and a good dispersion. Then a
solution containing 26.5 mg (0.25 mmol) of sodium carbon-
ate and 5 mL of water was added. The reaction was followed
and monitored by TLC. After the reaction was completed
(1 h), the aldol product was collected by Bu¨chner filtration,
washed with water (20 mL × 3), air-dried to give 267 mg
(98%) of 3aa as white powder. The purity of the 3aa was
Conclusions
1
over 99%, as determined by H NMR spectroscopy.
The present contribution describes the utilization of Na2-
CO3 as an efficient catalyst for the aldol reactions of
unmodified ketones and reactive aldehydes in pure water at
ambient temperature. An environmentally friendly and ef-
ficient process for the synthesis of â-hydroxyl ketones has
been proven to be practical from the aldol reaction of ketones
and reactive aldehydes bearing strong electron-withdrawing
groups. The current method presents a very attractive and
appealing synthetic process for â-hydroxyl ketones because
of the following advantages: (1) 100% atom economical
reaction, (2) very high yield and chemoselectivity, (3)
simplicity of product isolation, (4) usage of water as
environmentally benign reaction medium, (5) catalytic usage
of very cheap and readily available Na2CO3. The protocol
reported in this paper can be easily developed into large-
scale preparation of â-hydroxyl ketones, and the work along
this line is under way.
Other aldol products were prepared similarly. The threo
(anti) and erythro (syn) isomers of aldols 3ca, 3cb, and 3cc
were further separated by column chromatography on silica
gel with 2:1 petroleum ether/ethyl acetate.
The identities of 3ca isomers were confirmed by com-
parison of their spectral data with those reported before.10a,13,16
1
Part of the H NMR spectral data of 3ba were reported,17
but it seems that the reported data are not consistent with its
structure. The melting points and spectral data of all adol
products 3 except those of 3ca as well as of 3-(3,4-
dichlorophenyl)-3-hydroxy-1-(2-pyridyl)-1-propanone are listed
below.
3-(4-Nitrophenyl)-3-hydroxy-1-(2-pyridyl)-1-pro-
panone (3aa): mp 107-109 °C; 1H NMR (400 MHz,
CDCl3) δ 8.69 (ddd, J ) 4.7, 1.7, 0.9 Hz, 1 H), 8.22 (d, J
) 8.7 Hz, 2 H), 8.08 (dt, J ) 7.9, 1.0 Hz, 1 H), 7.90 (td, J
) 7.7, 1.7 Hz, 1 H), 7.63 (d, J ) 8.7 Hz, 2 H), 7.54 (ddd,
J ) 7.6, 4.7, 1.2 Hz, 1 H), 5.39 (dt, J ) 8.8, 3.4 Hz, 1 H),
4.72 (d, J ) 3.6 Hz, 1 H), 3.65 (dd, J ) 16.8, 3.1 Hz, 1 H),
3.57 (dd, J ) 16.8, 8.8 Hz, 1 H). 13C NMR (100 MHz,
CDCl3) δ 200.37, 152.82, 150.81, 148.97, 147.40, 137.61,
127.88, 126.66 (2C), 123.81 (2C), 122.45, 69.62, 47.61; FT-
IR (cm-1) 3332, 1697, 1509, 1347; HRMS (+CI) calcd for
C14H13N2O4 (M + 1): 273.0875, found: 273.0867.
3-(3-Nitrophenyl)-3-hydroxy-1-(2-pyridyl)-1-pro-
panone (3ab): mp 62-63 °C; 1H NMR (400 MHz, CDCl3)
δ 8.70 (ddd, J ) 4.7, 1.7, 0.9 Hz, 1 H), 8.36 (t, J ) 1.9 Hz,
1 H), 8.15 (ddd, J ) 8.2, 2.2, 1.0 Hz, 1 H), 8.10 (dt, J )
7.9, 1.1 Hz, 1 H), 7.91 (td, J ) 7.7, 1.7 Hz, 1 H), 7.80 (dt,
J ) 8.4, 1.0 Hz, 1 H), 7.55 (ddd, J ) 7.6, 4.7, 1.2 Hz, 1 H),
7.54 (t, J ) 8.0 Hz, 1 H), 5.39 (dt, J ) 8.8, 3.2 Hz, 1 H),
4.70 (d, J ) 3.5 Hz, 1 H), 3.67 (dd, J ) 16.8, 3.1 Hz, 1 H),
3.57 (dd, J ) 16.8, 8.8 Hz, 1 H); 13C NMR (100 MHz,
CDCl3) δ 200.54, 152.85, 149.05, 148.52, 145.70, 137.66,
Experimental Section
General. Reagents and solvents were obtained from
commercial suppliers and were used without further purifica-
tion. All melting points were determined on a XT-4 binocular
microscope (Beijing Tech Instrument Co., China) and are
not corrected. Infrared spectra were recorded on a VECTOR-
12 infrared spectrometer in KBr pellet and reported in cm-1.
1H NMR spectra were recorded on BRUKER AV400 (400
MHz) spectrometer, chemical shifts (δ) are reported in parts
per million relative to tetramethylsilane. Splitting patterns
are designated as s, singlet; d, doublet; t, triplet; q, quartet;
m, multiplet; br, broad. 13C NMR spectra were recorded on
(14) (a) Davey, W.; Gwilt, J. R. J. Chem. Soc. 1957, 1008-1014. (b) Sinisterra,
J. V.; Garcia-Raso, A.; Cabello, J. A.; Marinas, J. M. Synthesis 1984, 502-
504. (c) Natekar, R. S.; Samant, S. D. Indian J. Chem. 1996, 35B, 1347-
1348. (d) Zheng, M.; Wang, L.; Shao, J.; Zhong, Q. Synth. Commun. 1997,
27, 341-354. (e) Iranpoor, N.; Zeynizadeh, B.; Aghapour, A. J. Chem.
Res. (S) 1999, 554-555. (f) Li, Z.; Zhang, Y.; Li, Q. J. Chem. Res. (S)
2000, 580-581.
(15) (a) Toda, F.; Tanaka, K.; Hamai, K. J. Chem. Soc., Perkin Trans. 1 1990,
3207-3209. (b) Iranpoor, N.; Kazemi, F. Tetrahedron 1998, 54, 9475-
9480.
(16) Nakadai, M.; Saito, S.; Yamamoto, H. Tetrahedron 2002, 58, 8167-8177.
(17) Sugasawa, T.; Toyoda, T.; Sasakura, K. Synth. Commun. 1979, 9, 515-
528.
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Vol. 8, No. 1, 2004 / Organic Process Research & Development

132.11, 129.56, 127.95, 122.64, 122.49, 121.04, 69.53, 47.75;
FT-IR (cm-1) 3436, 1697, 1529, 1351; HRMS (+CI) calcd
for C14H13N2O4 (M + 1): 273.0875, found: 273.0879.
3-(2-Nitrophenyl)-3-hydroxy-1-(2-pyridyl)-1-pro-
panone (3ac): mp 107-109 °C; 1H NMR (400 MHz, CDCl3)
δ 8.66 (ddd, J ) 4.7, 1.7, 0.9 Hz, 1 H), 8.09 (dt, J ) 7.9,
1.1 Hz, 1 H), 7.97 (dd, J ) 8.2, 1.3 Hz, 1 H), 7.94 (dd, J )
7.9, 1.4 Hz, 1 H), 7.89 (td, J ) 7.7, 1.7 Hz, 1 H), 7.65 (td,
J ) 7.6, 1.3, Hz, 1 H), 7.52 (ddd, J ) 7.6, 4.8, 1.3 Hz, 1 H),
7.43 (td, J ) 8.2, 1.4 Hz, 1 H), 5.88 (d, J ) 8.9 Hz, 1 H),
4.52 (s, 1 H), 3.84 (dd, J ) 17.5, 2.4 Hz, 1 H), 3.55 (dd, J
) 17.5, 9.0 Hz, 1 H); 13C NMR (100 MHz, CDCl3) δ 200.26,
152.84, 148.87, 147.31, 139.02, 137.29, 133.62, 128.32,
128.15, 127.61, 124.42, 122.20, 65.83, 46.91; FT-IR (cm-1)
3534, 1684, 1523, 1341; HRMS (+CI) calcd for C14H13N2O4
(M + 1): 273.0875, found: 273.0871.
3-(4-Nitrophenyl)-3-hydroxy-1-phenyl-1-propanone
(3ba): mp 112-114 °C; 1H NMR (400 MHz, CDCl3) δ 8.25
(d, J ) 8.7 Hz, 2 H), 7.95 (dd, J ) 8.4, 1.3 Hz, 2 H), 7.63
(d, J ) 8.7 Hz, 2 H), 7.62 (tt, J ) 8.4, 1.2 Hz, 1 H), 7.49 (t,
J ) 8.0 Hz, 2 H), 5.46 (dt, J ) 8.8, 3.2 Hz, 1 H), 3.82 (d,
J ) 3.2 Hz, 1 H), 3.42 (dd, J ) 17.9, 3.2 Hz, 1 H), 3.33
(dd, J ) 17.9, 8.8 Hz, 1 H); 13C NMR (100 MHz, CDCl3)
δ 199.52, 150.17, 147.41, 136.19, 134.03, 128.85 (2C),
128.16 (2C), 126.56 (2C), 123.82 (2C), 69.24, 46.97; FT-
IR (cm-1) 3497, 1669, 1514, 1340; HRMS (+CI) calcd for
C15H14NO4 (M + 1): 272.0923, found: 272.0914.
148.40, 143.37, 133.27, 129.38, 122.96, 122.11, 74.15, 57.23,
42.76, 30.84, 27.71, 24.76; FT-IR (cm-1) 3436, 1693, 1532,
1352; HRMS (+CI) calcd for C13H16NO4 (M + 1): 250.1079,
found: 250.1078.
2-(Hydroxyl(3-nitrophenyl)methyl)-cyclohexanone (3cb)
1
(erythro): mp 63-64 °C; H NMR (400 MHz, CDCl3) δ
8.19 (t, J ) 1.8 Hz, 1 H), 8.12 (ddd, J ) 8.0, 2.3, 1.1 Hz,
1 H), 7.67 (dt, J ) 8.2, 1.0 Hz, 1 H), 7.52 (t, J ) 8.0 Hz, 1
H), 5.49 (t, J ) 2.4 Hz, 1 H), 3.17 (d, J ) 3.3 Hz, 1 H),
1.49-2.68 (m, 9 H); 13C NMR (100 MHz, CDCl3) δ 214.20,
148.44, 143.88, 132.03, 129.24, 122.18, 120.97, 70.02, 56.86,
42.71, 27.97, 26.01, 24.86; FT-IR (cm-1) 3434, 1691, 1525,
1353; HRMS (+CI) calcd for C13H16NO4 (M + 1): 250.1079,
found: 250.1078.
2-(Hydroxyl(2-nitrophenyl)methyl)-cyclohexanone (3cc)
1
(threo): mp 123-125 °C; H NMR (400 MHz, CDCl3) δ
7.84 (dd, J ) 8.2, 1.2 Hz, 1H), 7.77 (dd, J ) 7.9, 1.4 Hz, 1
H), 7.63 (td, J ) 7.7, 1.1 Hz, 1 H), 7.43 (td, J ) 8.2, 1.4
Hz, 1 H), 5.44 (d, J ) 7.1 Hz, 1 H), 3.95 (br, 1 H), 1.57-
2.79 (m, 9 H); 13C NMR (100 MHz, CDCl3) δ 214.97,
148.84, 136.70, 133.12, 129.09, 128.46, 124.15, 69.87, 57.39,
42.90, 31.20, 27.83, 25.06; FT-IR (cm-1) 3430, 1701, 1523,
1344; HRMS (+CI) calcd for C13H16NO4 (M + 1): 250.1079,
found: 250.1076.
2-(Hydroxyl(2-nitrophenyl)methyl)-cyclohexanone (3cc)
1
(erythro): mp 86-87 °C; H NMR (400 MHz, CDCl3) δ
8.00 (dd, J ) 8.2, 1.3 Hz, 1 H), 7.84 (dd, J ) 7.9, 1.4 Hz,
1 H), 7.65 (td, J ) 7.7, 1.3 Hz, 1 H), 7.43 (td, J ) 8.2, 1.5
Hz, 1 H), 5.96 (d, J ) 2.1 Hz, 1 H), 2.95(br, 1 H), 1.48-
2.90 (m, 9 H); 13C NMR (100 MHz, CDCl3) δ 214.05,
147.21, 137.08, 133.19, 129.68, 127.99, 124.71, 66.73, 54.90,
42.62, 28.05, 26.57, 24.92; FT-IR (cm-1) 3422, 1701, 1523,
1336; HRMS (+CI) calcd for C13H16NO4 (M + 1): 250.1079,
found: 250.1076.
3-(3-Nitrophenyl)-3-hydroxy-1-phenyl-1-propanone
1
(3bb): mp 82-84 °C; H NMR (400 MHz, CDCl3) δ 8.34
(s, 1 H), 8.17 (d, J ) 8.2 Hz, 1 H), 7.96 (d, J ) 7.9 Hz, 2
H), 7.80 (d, J ) 8.0 Hz, 1 H), 7.62 (t, J ) 7.4 Hz, 1 H),
7.57 (t, J ) 7.8 Hz, 1 H) 7.50 (t, J ) 7.8 Hz, 2 H), 5.46 (dt,
J ) 8.9, 3.1 Hz, 1 H), 3.83 (d, J ) 3.0 Hz, 1 H), 3.45 (dd,
J ) 17.8, 3.0 Hz, 1 H), 3.36 (dd, J ) 17.8, 8.9 Hz, 1H); 13
C
NMR (100 MHz, CDCl3) δ 199.78, 148.54, 145.15, 136.27,
134.17, 132.10, 129.69, 128.97 (2C), 128.30 (2C), 122.76,
121.02, 69.22, 47.10; FT-IR (cm-1) 3511, 1672, 1528, 1350;
HRMS (+CI) calcd for C15H12NO3 (M - 18 + 1): 254.0817,
found: 254.0809.
3-(3,4-Dichlorophenyl)-3-hydroxy-1-(2-pyridyl)-1-pro-
panone: mp 41-43 °C; 1H NMR (400 MHz, CDCl3) δ 8.68
(ddd, J ) 4.7, 1.7, 0.9 Hz, 1 H), 8.08 (dt, J ) 7.9, 1.1 Hz,
1 H), 7.88 (td, J ) 7.7, 1.7 Hz, 1 H), 7.57 (d, J ) 2.1 Hz,
1H), 7.52 (ddd, J ) 7.6, 4.8, 1.3 Hz, 1 H), 7.41 (d, J ) 8.3
Hz, 1 H), 7.27 (ddd, J ) 8.3, 2.1, 0.6 Hz, 1 H), 5.24 (dt, J
) 7.8, 3.9 Hz, 1 H), 4.52 (d, J ) 3.5 Hz, 1 H), 3.59 (dd, J
3-(2-Nitrophenyl)-3-hydroxy-1-phenyl-1-propanone
1
(3bc): mp 106-107 °C; H NMR (400 MHz, CDCl3) δ
7.96-8.01 (m, 3H), 7.70 (td, J ) 7.6, 1.3, 1 H), 7.60 (tt, J
) 7.4, 1.3 Hz, 1 H), 7.45-7.50 (m, 3H), 5.86 (dt, J ) 9.4,
2.6 Hz, 1 H), 4.01 (d, J ) 3.1 Hz, 1 H), 3.73 (dd, J ) 17.7,
2.2 Hz, 1 H), 3.22 (dd, J ) 17.7, 9.3 Hz, 1 H); 13C NMR
(100 MHz, CDCl3) δ 199.90, 147.32, 138.58, 136.34, 133.82
(2C), 128.75 (2C), 128.43, 128.31, 128.24 (2C), 124.44,
65.95, 46.46; FT-IR (cm-1) 3507, 1661, 1530, 1351; HRMS
(+CI) calcd for C15H14NO4 (M + 1): 272.0923, found:
272.0922.
2-(Hydroxyl(3-nitrophenyl)methyl)-cyclohexanone (3cb)
(threo): mp 84-85 °C; 1H NMR (400 MHz, CDCl3) δ 8.22
(t, J ) 1.8 Hz, 1 H), 8.16 (ddd, J ) 8.0, 2.3, 1.1 Hz, 1 H),
7.68 (dt, J ) 8.0, 1.0 Hz, 1 H), 7.53 (t, J ) 8.0 Hz, 1 H),
4.90 (dd, J ) 8.4, 3.1 Hz, 1 H), 4.10 (d, J ) 3.1 Hz, 1 H),
1.34-2.66 (m, 9 H); 13C NMR (100 MHz, CDCl3) δ 214.90,
) 16.8, 4.1 Hz, 1 H), 3.54 (dd, J ) 16.8, 7.9 Hz, 1 H); 13
C
NMR (100 MHz, CDCl3) δ 200.50, 152.86, 148.90, 143.75,
137.41, 132.56, 131.29, 130.39, 127.91, 127.68, 125.17,
122.28, 69.20, 47.52; FT-IR (cm-1) 3352, 1704; HR MS
(+CI) calcd for C14H9NO37Cl2 (M - 18): 281.0002, found:
280.9993.
Acknowledgment
This project is supported by the National Science Fund
for Distinguished Young Scholars (20125205), Anhui Pro-
vincial Natural Science Foundation (00045306), and Anhui
Provincial Bureau of Personnel Affairs.
Received for review September 5, 2003.
OP0341263
Vol. 8, No. 1, 2004 / Organic Process Research & Development
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