Quaternary ammonium salt gemini surfactants containing perfluoroalkyl tails catalyzed one-pot Mannich reactions in aqueous media

Article abstract of DOI:10.1016/j.jfluchem.2007.12.002

A newly prepared quaternary ammonium salt (QAS) gemini fluorosurfactants efficiently catalyze one-pot Mannich reactions of aldehydes, amines and ketones in aqueous media at ambient temperature to afford corresponding β-aminocarbonyl compounds in good to excellent yields. In addition, the gemini fluorosurfactant catalysts were recovered and reused for three times with little loss of their catalytic activities.

Full text of DOI:10.1016/j.jfluchem.2007.12.002

Available online at www.sciencedirect.com
Journal of Fluorine Chemistry 129 (2008) 267–273
www.elsevier.com/locate/fluor
Quaternary ammonium salt gemini surfactants containing perfluoroalkyl
tails catalyzed one-pot Mannich reactions in aqueous media
a
Wei Shen a, Li-Min Wang a,b, , He Tian
*
a Laboratory for Advanced Materials, Institute of Fine Chemicals, East China University of Science and Technology, 130 Meilong Road,
Shanghai 200237, People’s Republic of China
b Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Road,
Shanghai 200032, People’s Republic of China
Received 2 October 2007; received in revised form 9 December 2007; accepted 10 December 2007
Available online 23 December 2007
Abstract
A newly prepared quaternary ammonium salt (QAS) gemini fluorosurfactants efficiently catalyze one-pot Mannich reactions of aldehydes,
amines and ketones in aqueous media at ambient temperature to afford corresponding b-aminocarbonyl compounds in good to excellent yields. In
addition, the gemini fluorosurfactant catalysts were recovered and reused for three times with little loss of their catalytic activities.
# 2007 Elsevier B.V. All rights reserved.
Keywords: Quaternary ammonium salt (QAS); Gemini fluorosurfactant; Mannich reaction; b-Aminocarbonyl compound; Lewis acid
1. Introduction
synthesis as catalyst. Heavy fluorous catalysts whose molecules
contain more than 60% fluorine by molecular weight had been
widely used to provide a facile liquid/liquid separation after
reaction [10], but fluorous solvents used are expensive and
environmentally troublesome. Meanwhile, QAS containing
perfluoroalkyl tails, which shows excellent water solubility and
surfactivity, can disperse hydrophobic organic substrate in
water homogeneously. As a quaternary ammonium salt, they
can also play the role of phase transfer catalyst. Combining
these two roles together, fluorous QAS surfactants can be used
as a fluorous catalyst soluble in water instead of fluorous
solvent.
Considerable effort has been made by chemists to obtain a
consistent surface tension as low as possible (approximately
20 dyn/cm) [1]. But it resulted in the problem that the
surfactants consisting of long hydroalkyl tails [2]. Meanwhile
the corresponding value reported for perfluoroalkyl tailed
surfactant is from 6 to 13 dyn/cm. It is the –CF2– especially
the –CF3 end group in the molecule that effectively reduces
the surface tension to such extent [3]. Since perfluoroalkyl
chains are more hydrophobic than their alkyl analogues, the
critical micelle concentration (cmc) of perfluoroalkyl
surfactants is commonly one to two orders of magnitude
lower than that of hydrocarbon surfactants of similar length
[4–6].
The use of water as a sole medium for organic reactions
would greatly contribute to the development of environmen-
tally friendly processes. Recently, some organic reactions have
been realized in water [11]. Among these reactions, Mannich
reaction being carried out in water attracted much attention
[12]. The main catalysts reported include Lewis acids such as
triflates [12d,h] and chlorides [12e], Brønsted acids such as
sulfonic acids [12a,b,f,g], hydrochloric acid [12i] and hetero-
poly acids [12j]. However, when some parent ketones rather
than their silyl enolates forms are used directly, some Lewis
acids, which results in long reaction time [12e], are not effective
catalysts. And there are few reports on effectively catalyzed
reaction of anisaldehyde with aniline and acetophenone.
As antibacterial materials, fluorous QAS surfactants,
including gemini QAS fluorosurfactants, attached much
attention [7–9]. However, there are few or only limited reports
about QAS containing perfluoroalkyl tails used in organic
* Corresponding author at: Laboratory for Advanced Materials, Institute of
Fine Chemicals, East China University of Science and Technology, 130 Mei-
long Road, Shanghai 200237, People’s Republic of China.
Tel.: +86 21 64253881; fax: +86 21 64252758.
E-mail address: wanglimin@ecust.edu.cn (L.-M. Wang).
0022-1139/$ – see front matter # 2007 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2007.12.002

268
W. Shen et al. / Journal of Fluorine Chemistry 129 (2008) 267–273
Scheme 1.
Additionally, vigorous stirring was required for the success of
these reactions due to the poor solubility of aldehydes, ketones
and amines in water. To solve this problem, surfactants were
added to form colloidal dispersions as reaction media. Use of
surfactants can not only disperse organic substrate in water, but
also can make organic synthesis inside substrate-containing
particles in water [13]. Our group had reported a facile and
efficient method for preparation of b-aminocarbonyl com-
pounds by Mannich reaction of acetophenone with aldehydes
and aromatic amines in the presence of rare earth perfluor-
ooctanoate [RE(PFO)3] [14]. Herein, we would like to report a
new type of fluorous QAS gemini surfactant (compound 3)
used as a catalyst for one-pot Mannich reaction in water without
any organic solvent, and another three QAS surfactants
(compound 4–6) have also been prepared for control
experiments (Scheme 1).
mine to afford N-(2-(dimethylamino)propyl)-perfluorooctane-
sulfonamide 2 in 89% yield. Compound 2 can be quaternarized
with different alkyl halide in the tertiary amine functional group
to form many kinds of QAS. When 4,40-bis(chloromethyl)-1,10-
biphenyl and benzyl chloride were used as quaternarization
reagents, QAS 3 and 4 were obtained from the above reactions
in anhydrous EtOH–DMF–CHCl3 system in 67% and 82%
yield, respectively. Both of these two QAS 3 and 4 were soluble
in water.
2.2. Surface properties of QAS
The partially fluorinated quaternary ammonium salts 3
(GFQAS) and 4 (FQAS) exhibit good solubility in water at
room temperature. Fig. 1 shows that the curve of equilibrium
surface tension obtained from Wilhelmy plate method as a
function of the concentration of gemini surfactant 3 (GFQAS).
The value of the cmc obtained by the surface tension curve is
consistent with the concentration of break points. The cmc and
surface tension values at cmc (gcmc) of the four QAS are
summarized in Table 1.
2. Results and discussion
2.1. Synthesis
For our target molecule, biphenyl is chosen as the spacer
connecting two amphiphilic moieties, which is more rigid than
methylene groups. The strategy to prepare perfluoroalkyl
quaternary ammonium compounds 3 and 4 are shown in
Scheme 2. Perfluorooctanesulfonyl fluoride 1 is treated with
N,N-dimethylpropyl-1,3-diamine in the presence of triethyla-
As shown in Table 1, the fluorinated QAS surfactants exhibit
much smaller cmc values than their hydrocarbon counterparts.
Moreover, the surface tension at cmc (gcmc) reduced by
fluorinated QAS is much lower than that of hydrocarbon QAS.
The cmc of 3 (GFQAS) is one order of magnitude lower than its
counterpart 5 (GQAS), which corresponds to the equivalence of
Scheme 2.

W. Shen et al. / Journal of Fluorine Chemistry 129 (2008) 267–273
269
Fig. 2. Photographs of 3 (GFQAS) catalyzed reaction in water. The emulsion of
catalyst and reagents formed at the beginning of reaction (I) and the product
precipitated after the reaction finished (II). Upper layer: the catalytic mother
solution; lower layer: the crude product.
surfactant not only exhibit excellent micelle catalysis but also
phase transfer catalysis activity. Studies showed that
1.2 ꢀ 10ꢁ6 mol% (concentration reached at cmc with this
amount) of 3 just afforded poor yield (entry 2, Table 2), while
0.2 mol% of this catalyst gave satisfactory yield. It is mainly
because too little amount of 3 could not carry out phase transfer
catalysis effectively. After the reaction was completed, the
desired product was congregated and precipitated (Fig. 2);
hereby it could simply be separated by filtration. As showed in
Fig. 2, when the solution of catalyst was mixed with organic
substrates such as benzaldehyde, a white emulsion formed
through surfactant colloid dispersions (Fig. 2I). Then, after
reaction was finished, the product depositing out of the reaction
mixture could be isolated by filtration (Fig. 2II). Meanwhile,
the catalyst remained in the mother solution, which could be
reused for several times without obvious loss of activity (entry
11, Table 2). The yields were obtained from 83% to 78% (with
yields of product 2a being 83%, 81%, and 78% in the first,
second and third run, respectively). In view of environmental
benign methodologies, recovery and reuse of the reaction
media is highly preferable.
Fig. 1. Surface tension against log (concentration of 3 GFQAS).
Table 1
Cmc of surfactants and surface tension (ST) at each of their cmc at 25 8C
3 (GFQAS)
5.54 ꢀ 10ꢁ7
4 (FQAS)
5 (GQAS)
6 (TQAS)
cmc (mol/l)
3.22 ꢀ 10ꢁ5
2.98 ꢀ 10ꢁ6
9.35 ꢀ 10ꢁ4
ST (dyn/cm) 23.15
23.69
45.06
46.86
1 CF2 to 1.5 CH2 units [15]. The excellent surfactivity of 3
(GFQAS) mainly attributes the access to intensive hydrophobic
property of the long fluorocarbon chain. Besides, the biphenyl
group connecting two amphiphilic moieties more rigidly than
methylene groups, can also bring surface tension down to such
extent.
2.3. Catalytic activities of QAS
QAS could serve both as a phase transfer catalyst and as a
surfactant. Thus, we next investigated their catalytic activities
for three-component Mannich-type reactions of benzaldehyde
with aniline and acetophenone in water at room temperature.
First, the reaction was carried out in the presence of QAS
catalyst, and sodium hydroxide (NaOH) was chosen as a
Brønsted base (Scheme 3). The results were summarized in
Table 2.
The model reaction was also carried out using Brønsted
acid-surfactant combined catalysts, where p-tolylsulfonic acid
(TsOH) was chosen as the Brønsted acid (Table 3). Compared
with Brønsted base-surfactant systems, the reactions proceed-
ing under acidic conditions were slow, and the yields were not
Table 2
Mannich-type reactions in the presence of various catalysts under basic aqueous
media conditions at room temperaturea
It was found that with only 0.2 mol% of the 3 (GFQAS), the
reaction gave quite satisfactory yield at room temperature
within 6 h. Other QAS, especially the hydrocarbon ones only
gave moderate yields, but with more dosage. Furthermore, the
phase transfer catalyst triethylbenzylammonium chloride
(TEBA), which shows weak emulsification ability, can promote
the reaction even more effectively than sodium p-dodecylben-
zenesulfonate (SDBS). That is, the fluorous QAS gemini
Entry
Catalyst
Amount (mol%)/
conc. (mol/l)
Time
(h)
Yield
(%)b
1
2
None
–
6
6
6
6
6
6
6
6
6
6
6
18
3 (GFQAS)
3 (GFQAS)
3 (GFQAS)
4 (FQAS)
5 (GQAS)
5 (GQAS)
6 (TQAS)
SDBS
1.2 ꢀ 10ꢁ6/cmc
0.02/1.0 ꢀ 10ꢁ4
0.2/0.001
0.5/0.0025
1/0.005
21
3
40
4
83
5
53
6
39
7
2/0.01
56
8
2/0.01
43
9
5/0.025
39
10
11
TEBA
5
63
83, 81, 78c
3 (GFQAS)
0.2/0.001
a
In 10% sodium hydroxide solution.
Isolated yields.
b
c
Scheme 3.
The catalytic mother solution was reused for three times.

270
W. Shen et al. / Journal of Fluorine Chemistry 129 (2008) 267–273
Scheme 4.
Table 3
cyclohexanone gave the desired products, but a prolonged time
was need for the reaction of acetophenone. It is noteworthy that
reaction in basic media proceeded much more quickly than that
in acidic media. For example, the reaction of anisaldehyde with
aniline and acetophenone proceeded smoothly under basic
aqueous conditions to give the product in moderate yield, but it
did not provide the product under acidic aqueous conditions
(Tables 4 and 5). In general, aromatic aldehydes substituted
with electron withdrawing group gave higher yields than that
substituted with electron donating group. However, 4-nitro-
benzaldehyde provided only imine as the final product, while 3-
nitrobenzaldehyde gave the desired product in good yield. In
addition, aliphatic aldehydes, such as isobutyaldehyde, showed
a relatively lower yield even with prolonged reaction time due
to enamine formation.
Mannich-type reactions in the presence of various catalysts under acidic
aqueous media conditions at room temperature
Entry
Catalyst
Amount (mol%)
Time (h)
Yield (%)a
1
2
3
4
5
TsOH
10
12
12
12
12
12
Trace
70
3 (GFQAS) + TsOH
4 (FQAS) + TsOH
5 (GQAS) + TsOH
SDBS + TsOH
0.2 + 10
0.5 + 10
2 + 10
5 + 10
53
56
46
a
Isolated yields.
as high as above. Nevertheless, it would be noteworthy that the
highest yield was achieved by the use of GFQAS 3 as low as
0.2 mol% (entry 2) (Scheme 4).
In order to show the general applicability of the method, the
reactions of various aldehydes with aromatic amines and
ketones (1a or 1b) were carried out under basic and acidic
conditions. It was found that acetophenone in basic conditions
gave good to excellent yields, while cyclohexanone afforded no
products (Table 4). In acidic conditions both acetophenone and
Table 5
Synthesis of different b-aminocarbonyl compounds using 3 (GFQAS) as
catalysta
Entry R1
R2
Ketone Ketone Time Product Yield
(equiv.)b (h)
(%)c
Table 4
1
2
C6H5
H
1a
4-CH3 1a
4-MeO 1a
2
2
2
2
2
2
2
2
2
5
5
5
5
5
5
12
12
12
12
12
12
12
24
12
4
2a
2b
2c
2d
2e
2f
70
Synthesis of different b-aminocarbonyl compounds using 3 (GFQAS) as
catalysta
C6H5
74
3
C6H5
79
4
4-NO2C6H4
4-FC6H4
4-ClC6H4
4-ClC6H4
4-MeOC6H4
H
1a
1a
1a
1a
1a
1a
1b
1b
1b
1b
1b
1b
Imine
33
Entry R1
R2
Ketone Ketone
Time Product Yield
(%)c
5
H
(equiv.)b (h)
6
H
79
1
2
C6H5
H
1a
4-CH3 1a
4-MeO 1a
2
2
2
2
2
2
2
2
2
5
5
5
5
5
5
6
6
2a
2b
2c
2d
2e
2f
83
7
4-Cl
H
2g
2h
2i
82
C6H5
87
8
trace
3
C6H5
6
90
9
4-MeOC6H4 4-Cl
72
4
4-NO2C6H4
4-FC6H4
4-ClC6H4
4-ClC6H4
4-MeOC6H4
H
1a
1a
1a
1a
1a
1a
1b
1b
1b
1b
1b
1b
6
Imine
61
10
11
12
13
14
15
C6H5
H
H
2j
83 (44:56)d,e
87 (52:48)
82 (49:51)
73 (43:57)
45 (–)f
78 (71:29)
5
H
6
3-NO2C6H4
4
2k
2l
6
H
6
91
4-NO2C6H4 4-Cl
4-MeOC6H4 4-Cl
12
6
7
4-Cl
H
6
2g
2h
2i
85
2m
2n
2o
8
10
8
68
Me2CH
2-Furyl
H
H
12
12
9
4-MeOC6H4 4-Cl
80
10
11
12
13
14
15
C6H5
H
H
6
2j
Trace
Trace
Trace
Trace
Trace
Trace
a
All reactions were carried out in the presence of 10 mol% TsOH at room
3-NO2C6H4
6
2k
2l
temperature.
b
4-NO2C6H4 4-Cl
4-MeOC6H4 4-Cl
6
Both of aldehyde and aromatic amine used are 1 equiv.
6
2m
2n
2o
c
d
e
Isolated yields.
Me2CH
2-Furyl
H
H
6
syn/anti-ratio.
syn/anti-ratio was determined by 1H NMR spectroscopy of the crude
6
a
b
c
All reactions were carried out in 10% NaOH solution at room temperature.
Both of aldehyde and aromatic amine used are 1 equiv.
Isolated yields.
products and by comparison with known compounds reported in the literature
[12b,f,i,j].
f
The crude product is a complicated mixture due to enamine formation.

W. Shen et al. / Journal of Fluorine Chemistry 129 (2008) 267–273
271
3. Conclusions
J = 5.6 Hz), 2.88 (t, 4H, J = 5.6 Hz), 3.01 (s, 12H), 4.58 (d,
4H, J = 8.0 Hz), 7.68 (m, 4H), 7.85 (t, 4H, J = 8.0 Hz); 19F
NMR (470 MHz, DMSO-d6): d = ꢁ82.76 (t, 6F, J = 9.4 Hz),
ꢁ114.82 (t, 4F, J = 14.2 Hz), ꢁ122.09 (m, 4F), ꢁ123.31 (m,
4F), ꢁ123.44 (m, 4F), ꢁ123.59 (m, 4F), ꢁ124.40 (m, 4F),
ꢁ127.88 (m, 4F); MS (EI) m/z 1419 (M+). Anal. calcd. for
C40H38Cl2F34N4O4S2: C, 33.91; H, 2.49. Found: C, 33.94; H,
2.50.
In summary, a fluorinated QAS gemini surfactants were
prepared and served as a highly effective catalyst for three-
component one-pot Mannich reactions in water at room
temperature to afford b-aminocarbonyl compounds in good to
excellent yields. The method presented an operationally simple,
environmentally benign workup procedure without using any
organic solvent. Besides, the mother liquid containing catalyst
fluorous QAS gemini surfactants could be easily recycled and
reused without obvious loss of activities.
4.2.3. Preparation of 4 (FQAS)
Compound 2 (3.42 g, 5.8 mmol) and chloromethylbenzene
(0.76 g, 6.0 mmol) were added to a solution of EtOH–DMF–
CHCl3 (2.5:3:1, 18 ml), followed by stirring at 100 8C for 5 h.
After cooling the reaction mixture to room temperature, the
crude product was precipitated by the addition of Et2O to the
resulting solution. The solid were filtered, washed with Et2O.
The crude product was recrystallized from EtOH and petroleum
ether to afford the desired product 4.
White solid; 82%yield;mp 174–177 8C; 1H NMR(400 MHz,
DMSO-d6): d = 2.36 (m, 2H), 2.70 (t, 2H, J = 6.4 Hz), 2.88 (t,
2H, J = 6.4 Hz), 3.11 (s, 6H), 4.60 (s, 2H), 7.34 (s, 2H), 7.53 (m,
1H), 7.76 (s, 2H); 19F NMR (470 MHz, DMSO-d6): d = ꢁ81.83
(t, 3F, J = 9.4 Hz), ꢁ113.18 (t, 2F, J = 14.0 Hz), ꢁ121.78 (m,
2F), ꢁ122.54 (m, 2F), ꢁ122.82 (m, 2F), ꢁ123.00 (m, 2F),
ꢁ123.81 (m, 2F), ꢁ127.22 (m, 2F); MS (EI) m/z 710 (M+). Anal.
calcd. for C20H20ClF17N2O2S: C, 33.79; H, 2.84. Found: C,
33.81; H, 2.86.
4. Experimental
4.1. Methods and apparatus
IR spectra were recorded on a Shimadzu IR-440 spectro-
meter. 1H NMR spectra were recorded on a BRUKER AM 400
(400 MHz) using TMS as an internal standard. 19F NMR
spectra were recorded on a BRUKER WP-500SY (470 MHz)
spectrometer and were taken with CFCl3 as an internal
standard. Coupling constants (J) are given in Hz. Mass spectra
were recorded on a Finnigan-MAT-8430 instrument using EI
ionization at 70 eV.
4.2. Preparation of fluorous quaternary ammonium salts
4.2.1. N-(2-(Dimethylamino)ethyl)-
perfluorooctanesulfonamide 2
4.3. Typical procedure for Mannich reaction catalyzed by 3
(GFQAS) in basic and acidic conditions
Perfluorooctanesulfonyl fluoride 1 (13.5 ml, 0.05 mol) was
added dropwise to a stirred solution of N,N-dimethylpropyl-
1,3-diamine (7.6 ml, 0.06 mol) in petroleum ether (50 ml) at
0 8C containing triethylamine (10.4 ml, 0.075 mol). The
mixture was stirred at room temperature for 4 h and then
filtered. The yellow residue was recrystallized from acetone to
provide compound 2.
White solid; 89% yield; mp 117–119 8C; 1H NMR
(400 MHz, CDCl3): d = 1.76 (m, 2H, CH2), 2.31 (s, 6H, 2ꢀ
CH3), 2.59 (t, 2H, J = 5.6 Hz, CH2), 3.49 (t, 2H, J = 5.6 Hz,
CH2); 19F NMR (470 MHz, CDCl3): d = ꢁ82.76 (t, 3F,
J = 9.4 Hz), ꢁ114.49 (t, 2F, J = 14.2 Hz), ꢁ122.06 (m, 2F),
ꢁ123.30 (m, 2F), ꢁ123.42 (m, 2F), ꢁ123.58 (m, 2F), ꢁ124.41
(m, 2F), ꢁ127.88 (m, 2F); MS (EI) m/z 584 (M+). Anal. calcd.
for C13H13F17N2O2S: C, 26.72; H, 2.24. Found: C, 26.73; H,
2.24.
3 (GFQAS) (14.2 mg, 0.01 mmol) was dissolved in water
(10 ml), and then NaOH (1 g) was added. After the solution was
cooled down to room temperature, benzaldehyde (5 mmol),
aniline (5 mmol), and acetophenone (10 mmol) were added
successively. After being stirred at the same temperature for the
period of time listed in the tables, the mixture was placed still
and the resulting solid was filtered, washed with water (3ꢀ
5 ml) and recrystallized from EtOH to give the pure product.
The filtrate that containing catalyst could be reused directly
as reaction media for next run without any treatment.
3 (GFQAS) (14.2 mg, 0.01 mmol) was dissolved in water
(10 ml), and then TsOH (95 mg, 0.5 mmol) was added.
Benzaldehyde (5 mmol), aniline (5 mmol), and cyclohexanone
(25 mmol) were added successively. After being stirred at the
same temperature for the period of time listed in the tables, a
saturated aq. NaHCO3 solution (10 ml) and brine (10 ml) were
added, and the mixture was extracted with ethyl acetate, washed
with brine, dried over Na2SO4, and concentrated. Purification
by silica gel chromatography gave the desired product.
4.2.2. Preparation of 3 (GFQAS)
Compound 2 (6.42 g, 11.0 mmol) and 4,40-bis(chloro-
methyl)-1,10-biphenyl (1.25 g, 5.0 mmol) were added to a
solution of EtOH–DMF–CHCl3 (2.5:3:1, 26 ml), followed by
stirring at 100 8C for 8 h. After cooling the reaction mixture to
room temperature, the resulting suspension precipitated by the
addition of Et2O. The solids were filtered, washed with Et2O.
The crude solid was recrystallized from EtOH and petroleum
ether to afford the desired product 3.
4.4. Spectral characterization of Mannich reaction
products
4.4.1. 1,3-Diphenyl-3-phenylamino-propan-1-one (2a)
mp 172–173 8C (lit. [12h]: 170–172 8C); 1H NMR
(400 MHz, CDCl3): d = 7.90–7.88 (m, 2H), 7.56–7.05 (m,
White solid; 67% yield; mp 209–210 8C; 1H NMR
(400 MHz, DMSO-d6): d = 2.36 (m, 4H), 2.70 (t, 4H,

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W. Shen et al. / Journal of Fluorine Chemistry 129 (2008) 267–273
10H), 6.66–6.62 (m, 1H), 6.56–6.53 (m, 1H), 5.00 (dd, 1H,
J = 5.2, 7.2 Hz), 4.56 (br, 1H), 3.52 (dd, 1H, J = 5.2, 16 Hz),
3.43 (dd, 1H, J = 7.6, 16 Hz); IR (KBr): 3387, 3021,
4.4.8. 3-(4-Methoxy-phenyl)-1-phenyl-3-phenylamino-
propan-1-one (2h)
mp 150–152 8C (lit. [12h]: 150–151 8C); 1H NMR
(400 MHz, CDCl3): d = 7.87–7.93 (m, 2H), 7.55–7.57 (m,
1H), 7.46 (t, 2H, J = 7.0 Hz), 7.35 (d, 2H, J = 8.4 Hz), 7.07–
7.11 (m, 2H), 6.83–6.86 (m, 2H), 6.70 (t, 1H, J = 7.6 Hz), 6.54
(d, 2H, J = 7.6 Hz), 4.96 (t, 1H, J = 6.4 Hz), 3.77 (s, 3H), 3.54
(d, 1H, J = 5.4 Hz), 3.34 (d, 1H, J = 7.6 Hz); IR (KBr): 3387,
1669 cmꢁ1
.
4.4.2. 1,3-Diphenyl-3-p-tolylamino-propan-1-one (2b)
1
mp 170–172 8C (lit. [16a]: 171 8C); H NMR (400 MHz,
CDCl3): d = 7.89–7.91 (m, 2H), 7.56–7.57 (m, 1H), 7.43 (t, 2H,
J = 7.4 Hz), 7.23 (d, 2H, J = 8.2 Hz), 7.08–7.13 (m, 4H), 6.68
(t, 1H, J = 7.4 Hz), 6.64 (d, 2H, J = 8.0 Hz), 4.98 (t, 1H,
J = 6.2 Hz), 3.44–3.58 (m, 2H), 2.30 (s, 3H); IR (KBr): 3386,
3021, 1668 cmꢁ1
.
4.4.9. 3-(4-Chloro-phenylamino)-3-(4-methoxy-phenyl)-1-
phenyl-propan-1-one (2i)
3020, 2939, 1689 cmꢁ1
.
1
mp 149–151 8C (lit. [16c]: 148 8C); H NMR (400 MHz,
CDCl3): d = 7.90–7.88 (t, 2H, J = 6.7 Hz), 7.58–7.54 (t, 1H,
J = 7.4 Hz), 7.46–7.42 (t, 2H, J = 8.0 Hz), 7.33–7.31 (m, 2H),
7.04–7.01 (m, 2H), 6.87–6.84 (m, 2H), 6.48–6.45 (m, 2H),
4.91–4.88 (t, 1H, J = 7.4 Hz), 4.57 (br, 1H), 3.77 (s, 3H), 3.50–
3.44 (dd, 1H, J = 5.6, 16 Hz), 3.41–3.35 (dd, 1H, J = 7.6,
4.4.3. 3-(4-Methoxy-phenylamino)-1,3-diphenyl-propan-1-
one (2c)
mp 124–125 8C (lit. [12h]: 130–132 8C); 1H NMR
(400 MHz, CDCl3): d = 7.91 (d, 2H, J = 8.0 Hz), 7.56 (t, 1H,
J = 7.2 Hz), 7.45 (t, 4H, J = 6.4 Hz), 7.33 (t, 2H, J = 7.4 Hz),
7.24 (s, 1H), 6.69 (d, 2H, J = 8.0 Hz), 6.53 (d, 2H, J = 8.4 Hz),
4.93 (t, 1H, J = 6.8 Hz), 4.30 (br, 1H), 3.70 (s, 3H), 3.51–3.38
16 Hz); IR (KBr): 3381, 3020, 1669 cmꢁ1
.
4.4.10. 2-(Phenyl-phenylamino-methyl)-cyclohexanone
(2j)
(m, 2H); IR (KBr): 3399, 2974, 1672, 1598 cmꢁ1
.
mp 135–137 8C (lit. [16d]: 139–140 8C); 1H NMR
(400 MHz, CDCl3, major/minor = 56:44): d = 7.39–7.30 (m,
5H), 7.24–7.22 (t, 2H, J = 7.6 Hz), 6.65–6.63 (d, 1H,
J = 4.4 Hz), 6.57–6.53 (d, 2H, J = 7.2 Hz), 4.81 (d, 0.44H,
J = 4.0 Hz), 4.64 (d, 0.56H, J = 7.2 Hz), 2.75–2.83 (m, 1H),
2.28–2.47 (m, 2H), 1.58–1.94 (m, 6H); IR (KBr): 3386, 2939,
4.4.4. (4-Nitro-benzylidene)-phenyl-amine (2d)
mp 89–91 8C (lit. [16b]: 93 8C); 1H NMR (400 MHz,
CDCl3): d = 8.57 (s, 1H), 8.36–8.33 (d, 2H, J = 8.8 Hz), 8.11–
8.09 (d, 2H, J = 8.8 Hz), 7.47–7.43 (t, 2H, J = 7.8 Hz), 7.33–
7.27 (m, 3H); IR (KBr): 3187, 3021, 1678, 1527, 1348 cmꢁ1
.
1689, 1500 cmꢁ1
.
4.4.5. 3-(4-Fluoro-phenyl)-1-phenyl-3-phenylamino-
4.4.11. 2-[(3-Nitro-phenyl)-phenylamino-methyl]-
propan-1-one (2e)
mp 111–113 8C (lit. [16a]: 111–112 8C); 1H NMR
(400 MHz, CDCl3): d = 7.90 (d, 2H, J = 7.0 Hz), 7.58 (t, 1H,
J = 7.0 Hz), 7.48–7.42 (m, 4H), 7.10 (t, 2H, J = 7.2 Hz), 7.01 (t,
2H, J = 8.2 Hz), 6.69 (t, 1H, J = 7.6 Hz), 6.55 (d, 2H,
J = 7.6 Hz), 5.00 (t, 1H, J = 7.4 Hz), 4.56 (br, 1H), 3.52–
cyclohexanone (2k)
mp 163–165 8C; 1H NMR (400 MHz, CDCl3, major/
minor = 52/48): d = 8.26–8.24 (d, 1H, J = 7.6 Hz), 8.09–8.07
(d, 1H, J = 8.0 Hz), 7.80–7.77 (m, 1H), 7.49–7.45 (t, 1H,
J = 8.0 Hz), 7.12–7.08 (t, 2H, J = 8.0 Hz), 6.70–6.66 (m, 1H),
6.54–6.52 (d, 2H, J = 8.0 Hz), 4.86 (d, 0.52H, J = 4.0 Hz), 4.84
(d, 0.48H, J = 5.2 Hz), 2.89–2.86 (m, 1H), 2.42–2.34 (m, 2H),
2.08–1.95 (m, 3H), 1.79–1.75 (m, 1H), 1.66–1.58 (m, 2H); IR
3.40 (m, 2H); IR (KBr): 3376, 3020, 1667 cmꢁ1
.
(KBr): 3386, 3021, 1673, 1527, 1348 cmꢁ1
.
4.4.6. 3-(4-Chloro-phenyl)-1-phenyl-3-phenylamino-
propan-1-one (2f)
mp 116–117 8C (lit. [12h]: 114–115 8C); 1H NMR
(400 MHz, CDCl3): d = 7.93 (d, 2H, J = 8.0 Hz), 7.60 (t, 2H,
J = 7.6 Hz), 7.50–7.40 (m, 2H), 7.05 (t, 2H, J = 8.4 Hz), 6.90 (t,
2H, J = 6.8 Hz), 6.52 (d, 2H, J = 7.6 Hz), 6.30 (t, 2H,
J = 7.6 Hz), 4.99 (t, 1H, J = 5.6 Hz), 4.57 (br, 1H), 3.52–
4.4.12. 2-[(4-Chloro-phenylamino)-(4-nitro-phenyl)-
methyl]-cyclohexanone (2l)
mp 169–171 8C; 1H NMR (400 MHz, CDCl3, major/
minor = 51/49): d = 8.18–8.16 (d, 2H, J = 8.8 Hz, Ar), 7.57–
7.53 (m, 2H, Ar), 7.05–7.02 (d, 2H, J = 8.8 Hz, Ar), 6.44–6.41
(d, 2H, J = 8.8 Hz, Ar), 4.80 (d, 0.49H, J = 5.8 Hz), 4.64 (d,
0.51H, J = 7.2 Hz), 2.86–2.83 (t, 1H, J = 6.2 Hz), 2.48–2.30
(m, 2H), 2.10–2.01 (m, 2H), 1.95–1.94 (d, 1H, J = 5.6 Hz),
1.80–1.58 (m, 3H); IR (KBr): 3386, 3021, 1673, 1527,
3.40 (m, 2H); IR (KBr): 3376, 3020, 1667 cmꢁ1
.
4.4.7. 3-(4-Chloro-phenyl)-3-(4-chloro-phenylamino)-1-
phenyl-propan-1-one (2g)
1
mp 155–157 8C (lit. [16c]: 155 8C); H NMR (400 MHz,
1348 cmꢁ1
.
CDCl3): d = 7.94–7.93 (d, 2H, J = 4.6 Hz), 7.63–7.60 (t, 1H,
J = 6.4 Hz), 7.51–7.48 (t, 2H, J = 6.0 Hz), 7.44–7.39 (m, 2H),
7.33–7.30 (t, 2H, J = 6.4 Hz), 7.08–7.06 (d, 2H, J = 8.0 Hz),
6.50–6.48 (d, 2H, J = 8.2 Hz), 4.98–4.96 (t, 1H, J = 4.6 Hz),
3.48–3.45 (t, 1H, J = 6.4 Hz), 2.21 (s, 2H); IR (KBr): 3378,
4.4.13. 2-[(4-Chloro-phenylamino)-(4-methoxy-phenyl)-
methyl]-cyclohexanone (2m)
mp 132–134 8C (lit. [16e]: 132–134 8C); 1H NMR
(400 MHz, CDCl3, major/minor = 57/43): d = 7.27–7.24 (t,
2H, J = 7.4 Hz), 7.01–6.99 (d, 2H, J = 8.2 Hz), 6.85–6.83 (d,
3020, 1668 cmꢁ1
.

W. Shen et al. / Journal of Fluorine Chemistry 129 (2008) 267–273
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2H, J = 8.2 Hz), 6.46–6.43 (d, 2H, J = 8.2 Hz), 4.75 (d, 0.43H,
J = 4.8 Hz), 4.59 (d, 0.57H, J = 6.4 Hz), 3.78 (s, 3H), 2.69–2.68
(m, 1H), 2.42–2.38 (m, 1H), 2.43–2.32 (m, 1H), 1.93–1.81 (m,
4H), 1.68–1.63 (m, 2H); IR (KBr): 3362, 2964, 1703, 1603,
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1431.
1512 cmꢁ1
.
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4.4.14. 2-(2-Methyl-1-phenylamino-propyl)-cyclohexanone
(2n)
1
mp 87–89 8C; H NMR (400 MHz, CDCl3): d = 7.16–7.12
(t, 2H, J = 8.0 Hz), 6.67–6.61 (m, 3H), 3.91–3.88 (dd, 1H,
J = 4.4, 7.6 Hz), 2.49–2.27 (m, 3H), 2.13–1.82 (m, 4H), 1.76–
1.59 (m, 3H), 0.96–0.88 (d, 6H, J = 6.4 Hz); IR (KBr): 3386,
2968, 2939, 1689 cmꢁ1
.
(d) C.J. Li, T.H. Chan, Organic Reactions in Aqueous Media, John Wiley,
New York, 1997;
4.4.15. 2-(Furan-2-yl-phenylamino-methyl)-cyclohexanone
(2o)
(e) P.E. Grieco, Organic Reactions in Water, Blackie Academic &
Professional, London, 1998;
mp 120–121 8C; 1H NMR (400 MHz, CDCl3, major/
minor = 71/29): d = 7.29–7.10 (m, 3H), 6.71–6.61 (m, 3H),
6.26–6.17 (m, 2H), 4.88 (d, 0.71H, J = 4.8 Hz), 4.82 (d, 0.29H,
J = 5.4 Hz), 4.5 (br, 1H), 2.99–2.89 (m, 1H), 2.40–1.60 (m,
(f) U.M. Lindstrom, Chem. Rev. 102 (2002) 2751–2772;
(g) C.J. Li, Chem. Rev. 105 (2005) 3095–3166;
(h) N. Eghbali, C.J. Li, Green Chem. 9 (2007) 213–215.
[12] (a) K. Manabe, Y. Mori, S. Kobayashi, Synlett (1999) 1401–1402;
(b) K. Manabe, S. Kobayashi, Org. Lett. 1 (1999) 1965–1967;
(c) T. Akiyama, J. Takaya, H. Kagoshima, Synlett (1999) 1426–1428;
(d) S. Kobayashi, T. Busujima, S. Nagayama, Synlett (1999) 545–546;
(e) T.P. Loh, S.B. Liung, K.L. Tan, L.L. Wei, Tetrahedron 56 (2000)
3227–3237;
8H); IR (KBr): 3362, 2938, 1673, 1597, 1500 cmꢁ1
.
Acknowledgements
(f) K. Manabe, Y. Mori, S. Kobayashi, Tetrahedron 57 (2001) 2537–2544;
(g) S. Iimura, D. Nobutou, K. Manabe, S. Kobayashi, Chem. Commun.
(2003) 1644–1645;
This project was financially supported by the National
Nature Science Foundation of China (20672035) and Key
Laboratory of Organofluorine Chemistry, Shanghai Institute of
Organic Chemistry, Chinese Academy of Sciences.
(h) T. Ollevier, E. Nadeau, J. Org. Chem. 69 (2004) 9292–9295;
(i) T. Akiyama, K. Matsuda, K. Fuchibe, Synlett (2005) 322–324;
(j) N. Azizi, L. Torkiyan, M.R. Saidi, Org. Lett. 8 (2006) 2079–2082.
[13] K. Manabe, Y. Mori, T. Wakabayashi, S. Nagayama, S. Kobayashi, J. Am.
Chem. Soc. 122 (2000) 7202–7207.
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