Variation of xantphos-based ligands in the palladium-catalyzed reaction of aryl halides with ureas

Article abstract of DOI:10.1023/B:RUJO.0000019738.50339.e8

A series of Xantphos-based ligands containing various substituents in the diphenylphosphino groups were synthesized, and their effect on the product yield and ratio in the palladium-catalyzed arylation of ureas with nonactivated aryl halides was studied. The arylation of urea and phenylurea in the presence of Pd₂(dba)₃-CHCl₃, 3,5-(CF₃) ₂Xantphos, and Cs₂CO₃ in dioxane at 100°C gave the corresponding N,N′-diarylureas in 62-98% yield.

Full text of DOI:10.1023/B:RUJO.0000019738.50339.e8

Russian Journal of Organic Chemistry, Vol. 39, No. 12, 2003, pp. 1741 1752. Translated from Zhurnal Organicheskoi Khimii, Vol. 39, No. 12, 2003,
pp. 1814 1825.
Original Russian Text Copyright
2003 by Sergeev, Artamkina, Beletskaya.
Variation of Xantphos-Based Ligands in the Palladium-
Catalyzed Reaction of Aryl Halides with Ureas
A. G. Sergeev, G. A. Artamkina, and I. P. Beletskaya
Faculty of Chemistry, Moscow State University, Leninskie gory 1, Moscow, 119992 Russia
e-mail: gaa@elorg.chem.msu.ru
Received May 15, 2003
Abstract A series of Xantphos-based ligands containing various substituents in the diphenylphosphino
groups were synthesized, and their effect on the product yield and ratio in the palladium-catalyzed arylation
of ureas with nonactivated aryl halides was studied. The arylation of urea and phenylurea in the presence of
Pd2(dba)3 CHCl3, 3,5-(CF3)2Xantphos, and Cs2CO3 in dioxane at 100 C gave the corresponding N,N -diaryl-
ureas in 62 98% yield.
Arylureas are widely used as medicines [1], pes-
ticides [1], and receptors for selective binding of
anions [2] and in the synthesis of polymeric materials
[3]. Arylureas are usually prepared by reactions of
arylamines with isocyanates or carbonyl chloride [1].
Alternative routes include catalytic reductive car-
bonylation of nitroarenes [4] and oxidative carbonyla-
tion of amines [5]. Most of these procedures utilize
ecologically hazardous and toxic reagents.
In the recent years, palladium-catalyzed arylation
of amines (Buchwald Hartwig reaction) [6] has
become a convenient and effective method of building
up C N bonds. The scope of application of this
procedure was extended to include amides [7 10],
sulfonamides [8, 9], and ureas [11], which can be
subjected to arylation under mild conditions with
conservation of other functional groups. Xantphos
[8 11] turned out to be the most efficient ligand for
such palladium-catalyzed reactions. However, the use
of Xantphos is generally limited to reactions with
activated aryl halides. Analogous reactions with non-
activated substrates are difficult to accomplish. As
a rule, large amounts of the catalyst are necessary,
and the product yields are poor [8 11]. In many cases,
especially when aryl halide contains donor substit-
uents (e.g., methoxy group), the reaction fails to occur
[8, 10]. The same applies to the arylation of ureas,
which was studied by us previously: In the reactions
Scheme 1.
1070-4280/03/3912-1741$25.00 2003 MAIK Nauka/Interperiodica

1742
SERGEEV et al.
Scheme 2.
Ar = o-MeC6H4 (o-MeXantphos), p-MeOC6H4 (p-MeOXantphos), Ph (Xantphos), 3,5-(CF3)2C6H3 [3,5-(CF3)2Xantphos],
C6F5 (FluoroXantphos).
with activated aryl halides, the corresponding N,N -di-
arylureas are formed in high yelds, while the arylation
of urea with p-bromotoluene under analogous condi-
tions is characterized by incomplete conversion and
low yield of the target product and is accompanied by
formation of phenyl-substituted ureas [11]. Buchwald
et al. [12] recently showed that copper complexes in
the presence of diamine ligands effectively catalyze
arylation of amides with aryl bromides (including
nonactivated ones). However, we failed to effect
arylation of urea under the same conditions.
Scheme 1 shows the catalytic cycle in the arylation
reaction. Oxidative addition of even nonactivated aryl
bromides to palladium(0) complex occurs under very
mild conditions. In the presence of Xantphos, the
amination of phenyl bromide can be performed at
room temperature [13]. On the other hand, arylation
of amides with nonactivated aryl bromides requires
considerably more severe conditions (100 C) [8 11].
Therefore, the limiting stage in the reaction with
nonactivated aryl bromides is either transmetalation
or reductive elimination. In fact, increase in the donor
power of substituent in the aryl group is known to
hamper reductive elimination with formation of C N
bond [14]. Moreover, a considerable deceleration of
stages following the oxidative addition could give rise
to a variety of side processes. One of such processes
is exchange between the aryl group attached to palla-
dium and phenyl group of the phosphine ligand in
the complex Pd(L L)(Ar)Br [15]. The subsequent
transmetalation and reductive elimination leads to
formation of N-phenyl derivatives. The contribution
of the exchange process increases in parallel with the
donor power of the aryl group (Ar) [15]. Therefore,
problems concerning formation of N-phenyl com-
pounds as by-products and deactivation of the catalyst
become especially important in the reactions of
amides and ureas with nonactivated aryl bromides.
Taking into account that the rate of reductive elimina-
tion rises as the electron density on the palladium
atom decreases [16] and as the size of the ligand
increases [17], we anticipated that bulky phosphine
ligands having electron-acceptor substituents should
favor the process.
We have synthesized a series of ligands with dif-
ferent electronic and steric parameters on the basis
of Xantphos which is the most efficient ligand for
palladium-catalyzed amidation of aryl halides [8 11].
Steric and electronic parameters of the ligands were
varied via introduction of acceptor and donor substit-
uents into different positions of the phenyl rings and
via replacement of phosphorus by arsenic. Ligands L
were synthesized by metalation of 9,9-dimethylxan-
thene and subsequent addition of diaryl(chloro)phos-
phine or chloro(diphenyl)arsine at reduced tempera-
ture as shown in Scheme 2.
Table 1. Synthesis of Xantphos-based ligands
Run
no.
Temperature, C Yield,
Ligand (L)
second stage)
%
1
2
3
4
5
6
p-MeOXantphos
3,5-(CF3)2Xantphos
3,5-(CF3)2Xantphos
FluoroXantphos
FluoroXantphos
Xantharsine
20
0
60
20
90
65
34
7
30
a
The ligand yields in the reaction of metalated
dimethylxanthene with diaryl(chloro)phosphine having
electron-acceptor groups (F or CF3) strongly depended
on the temperature (Table 1, run nos. 2 5). When
12
53
a
Mixture of products.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 39 No. 12 2003

VARIATION OF XANTPHOS-BASED LIGANDS
Table 2. Palladium-catalyzed reaction of urea with p-bromotoluene in the presence of Xantphos-based ligands
Yield, %
1743
Run no.
Ligand (L)
Pd, mol %
Time, h
Conversion, %
A
B
C
1
p-MeOXantphos
4
2.5
24
20
2.5
20
20
34
47
62
100
9
8
4
2
3
4
5
6
Xantphos
4
4
4
2.5
2.5
7
62
10
8
5
3,5-(CF3)2Xantphos
o-MeXantphos
FluoroXantphos
Xantharsine
5
8
20
chlorobis(pentafluorophenyl)phosphine was added to
dilithium derivative of 9,9-dimethylxanthene at
20 C, a complex mixture of products was obtained
(run no. 4), from which we failed to isolate Fluoro-
Xantphos. The latter was isolated in a poor yield when
the reaction was carried out at 90 C (run no. 5).
Likewise, the yield of 3,5-(CF3)2Xantphos consider-
ably increased when the phosphine was added at
lower temperature (run nos. 2, 3).
We examined the efficiency of the prepared ligands
in the reaction of p-bromotoluene with urea. In the
presence of Xantphos, the conversion was incomplete,
and the yield of N,N -di-p-tolylurea was low (Table 2,
run no. 2). As catalyst precursor we used Pd2(dba)3
CHCl3, the palladium-to-ligand ratio was equal to 1.5,
and Cs2CO3 was added as a base. The reactions were
carried out in dioxane at 100 C (Table 2, Scheme 3).
The data in Table 2 show (run nos. 1 3) that the
conversion and product yields strongly depend on
the electronic properties of the phosphine ligand.
The conversion increases in going from donor p-MeO-
Xantphos to Xantphos, and it reaches 100% in the
presence of acceptor 3,5-(CF3)2Xantphos; moreover,
in the latter case, the formation of by-products B and
C is considerably suppressed. The yields of N,N -di-
p-tolylurea obtained with the use of p-MeOXantphos
and Xantphos are almost similar (7 8%; run nos. 1, 2).
Addition of 3,5-(CF3)2Xantphos as ligand increases
the yield of A to 62%, the conversion of p-bromo-
toluene being complete (run no. 3). Unexpected results
were obtained with ligands having bulky aryl substit-
uents. In the reactions with both donor o-MeXantphos
and acceptor FluoroXantphos, the conversion was
lower than 10%. Inefficiency of o-MeXantphos in
the arylation of amides was also noted by Buchwald
[9]. On the other hand, similar results were obtained
with o-MeXantphos and Xantphos in the arylation
of amines [18]. Replacement of the phosphorus atom
in Xantphos by arsenic did not increase the efficiency
(run no. 6). Thus, our experiments on ligand variation
showed that 3,5-(CF3)2Xantphos is the only ligand
efficient in the arylation of urea with p-bromotoluene.
Therefore, it was used in the arylation of urea with
nonactivated and weakly activated aryl halides
(Table 3, Scheme 4).
The results showed that 3,5-(CF3)2Xantphos is
clearly suprior to Xantphos. It ensures successful
arylation of urea with nonactivated aryl bromides, and
the yields of the corresponding N,N -diarylureas attain
61 98% (Table 3, run nos. 1, 3, 5, 7, 9, 10). ortho-
Substituted aryl bromides react much more readily
than the para isomers (yield 80 98%; run nos. 1, 3,
Scheme 3.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 39 No. 12 2003

1744
SERGEEV et al.
Scheme 4.
5, 7, 10). In the reaction of urea with o-bromochloro-
benzene in the presence of Xantphos, a considerable
amount of o,o -dichlorodiphenylamine (35%) was
formed in addition to the major product, N,N -bis-
(o-chlorophenyl)urea (57%, run no. 4), whereas di-
o-tolylamine was the only product (77%) in the reac-
tion with o-bromotoluene (run no. 8); i.e., in the latter
case replacement of the ligand changes the reaction
direction. It should also be noted that the arylation of
urea with p-bromochlorobenzene and p-bromotoluene
Table 3. Palladium-catalyzed arylation of urea with nonactivated aryl halides in the presence of 3,5-(CF3)2Xantphos
and Xantphos
Run
no.
Pd,
mol %
Time,
h
Conver- Yield,
Aryl halide
Ligand (L)
Product
sion, %
%
1
2
p-ClC6H4Br
3,5-(CF3)2Xantphos
Xantphos
2
4
2
10
100
100
81
64
3
4
o-ClC6H4Br
p-MeC6H4Br
o-MeC6H4Br
o-MeC6H4Br
3,5-(CF3)2Xantphos
Xantphos
1
4
5
11
100
100
91
57
5
6
3,5-(CF3)2Xantphos
Xantphos
4
4
2.5
20
100
62
62
7
7
3,5-(CF3)2Xantphos
Xantphos
1
4
100
98
8
9
4
2
3
36
4
94
100
100
77a
71
m-MeC6H4Br 3,5-(CF3)2Xantphos
10 o-MeOC6H4Br 3,5-(CF3)2Xantphos
11 p-MeOC6H4Br 3,5-(CF3)2Xantphos
4
80
b
2.5
4
4
2
4.5
5
29
15
27
12
3,5-(CF3)2Xantphos
13 o-Me2NC6H4Br 3,5-(CF3)2Xantphos
a
No N,N -di-o-tolylurea was formed.
Sodium tert-butoxide was used as a base.
b
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 39 No. 12 2003

VARIATION OF XANTPHOS-BASED LIGANDS
in the presence of 3,5-(CF3)2Xantphos requires Scheme 5.
1745
a smaller amount of the catalyst and gives greater
yields of the products, as compared to Xantphos (run
nos. 1, 2, 5 6).
Thus the use of 3,5-(CF3)2Xantphos as ligand
allowed us to effect successful reactions of urea with
nonactivated and weakly activated substrates which
afforded much less satisfactory yields of diarylureas
in the presence of Xantphos. However, the scope of
application of 3,5-(CF3)2Xantphos is also limited:
the reaction of urea with p-bromoanisole even with
2.5 mol % of the catalyst was characterized by a low
conversion (run no. 11) which we failed to improve
by the use of a stronger base, t-BuONa instead of
Cs2CO3 (run no. 12). Under analogous conditions,
the conversion of o-bromoanisole was 100%, and the
yield of N,N -bis(o-methoxyphenyl)urea was 80%
(run no. 10). o-Bromo-N,N-dimethylaniline did not
react with urea (run no. 13).
panied by formation of the corresponding symmetric
N,N -diarylureas and N,N -diphenylurea via dispropor-
tionation of the major product. The fraction of sym-
metric ureas increases with time. Insofar as reactions
of ureas with nonactivated aryl halides are fairly slow,
it seemed impossible to obtain under analogous condi-
tions unsymmtrically substituded N-aryl-N -phenyl-
ureas having donor groups in the aryl fragment.
However, using 3,5-(CF3)2Xantphos as ligand, we
succedeed in synthesizing such products in fairly high
yields (Scheme 5, Table 4; run nos. 1 3, 5, 7, 8). In
order to minimize the contribution of side processes,
We showed in [11] that arylation of phenylurea
with activated aryl bromides in the presence of Xant-
phos leads to unsymmetrically substituted N-aryl-N -
phenylureas in high yields. The reaction is accom-
Table 4. Palladium-catalyzed arylation of phenylurea with nonactivated aryl halides in the presence of 3,5-(CF3)2-
Xantphos and Xantphos as ligand (L)
Run
no.
Pd,
mol %
Time,
h
Conver- Yield,
Aryl halide
ClC6H4Br
Ligand (L)
Product
sion, %
%
1
2
3,5-(CF3)2Xantphos
3,5-(CF3)2Xantphos
2
1
1
1
100
72
o-ClC6H4Br
MeC6H4Br
100
95
3
4
3,5-(CF3)2Xantphos
Xantphos
3.5
4
1
1.5
100
63
80
37
5
6
o-MeC6H4Br
3,5-(CF3)2Xantphos
Xantphos
2.5
4
1
1.5
100
30
95
18
7
8
m-MeC6H4Br 3,5-(CF3)2Xantphos
o-MeOC6H4Br 3,5-(CF3)2Xantphos
2
4
1
1
100
100
81
91
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 39 No. 12 2003

1746
SERGEEV et al.
Scheme 6.
the reaction time was shortened by increasing the
amount of the catalyst. As in the reactions with urea,
ortho-substituted aryl halides turned out to be more
reactive substrates (run nos. 2, 5, 8). For comparison,
the conversion and yield in the reaction of phenylurea
with o-bromotoluene using Xantphos as ligand were
lower (run no. 6). In addition, o-bromotoluene was
less reactive than p-bromotoluene (run nos. 4, 6).
It is known that arylation of amides with strongly
deactivated aryl halides (like p-bromoanisole) in the
presence of Xantphos gives no acceptable yields of
the corresponding N-aryl derivatives [8, 10]. There-
fore, it was interesting to examine the arylation of
amides using 3,5-(CF3)2Xantphos as ligand. For this
purpose, p-bromoanisole was brought into reaction
with p-methylbenzamide in the presence of 2 mol %
of Pd2(dba)3 CHCl3 and 6 mol % of the ligand in
dioxane at 100 C (Scheme 6, Table 5). We did not
succeed in attaining complete conversion of the initial
aryl halide. However, the data in Table 3 (run nos. 11,
12) and Table 5 (run nos. 1, 2) indicate that the aryla-
tion of p-methylbenzamide occurs more readily than
the arylation of urea. In both cases, a considerable
amount of the aryl aryl exchange product, N-[3,5-bis-
(trifluoromethyl)phenyl]-4-methylbenzamide, was
formed (run nos. 1, 2). When the reaction was carried
in the presence of a stronger base (t-BuONa) and in
a more polar solvent, the yield and conversion were
reduced (run nos. 3, 4).
EXPERIMENTAL
Cesium carbonate was dried at 150 200 C under
reduced pressure. Dioxane, tetrahydrofuran, and di-
methylacetamide were dried and purified by standard
procedures. Dioxane and THF were stored over potas-
sium diphenylketyl in an evacuated vessel. The com-
plex Pd2(dba)3 CHCl3 [19], Xantphos [20], and
o-TolXantphos [18] were synthesized by known
methods. Aryl halides were purified by distillation or
recrystallization prior to use.
1
The H, 19F, and 31P NMR spectra were recorded
on a Varian VXR-400 spectrometer at 400, 376, and
161.90 MHz, respectively; the chemical shifts were
measured relative to signals of residual protons in the
deuterated solvent (1H), C6F6 (19F,
162.9 ppm
F
relative to CFCl3), and 85% H3PO4 (31P, external
reference). GLC analysis was performed on an Agat-9
Table 5. Palladium-catalyzed arylation of p-methylbenzamide with p-bromoanisole in the presence of 3,5-(CF3)2-
Xantphos as ligand
Yield, %
Run no.
1
Base
Solvent
Time, h
Conversion, %
I
II
Cs2CO3
Dioxane
2.5
8
26.5
21
51
73
75
41
42
37
35
21
18
19
2
3
4
K3PO4
t-BuONa
Cs2CO3
Dioxane
Dioxane
DMA
8.5
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 39 No. 12 2003

VARIATION OF XANTPHOS-BASED LIGANDS
1747
chromatograph equipped with a flame-ionization
detector; 2.5-m 5-mm column packed with OV-17
on Inerton Super (160 200 m); carrier gas nitrogen.
The mass spectra (electron impact, 70 eV) were run
on Kratos MS-30 and Kratos MS-890 instruments.
Taking into account considerable discrepancies in the
published melting points of some N,N -diarylureas,
only analytical data are given below for the products.
(4H), 7.61 s (8H), 7.57 d (2H, J = 7.7 Hz), 7.12 t (2H,
J = 7.7 Hz), 6.40 d (2H, J = 7.7 Hz), 3.78 s (12H),
1.67 s (6H). 31P {1H} NMR spectrum (CDCl3):
14.36 ppm. Mass spectrum, m/z (Irel, %): 1122
P
[M]+. Found, %: C 50.22; H 2.03. C47H24F24OP2.
Calculated, %: C 50.29; H 2.15.
9,9-Dimethyl-4,5-bis{bis[bis(3,5-trifluoromethyl)-
phenyl]phosphino}xanthene [3,5-(CF3)2Xantphos]
(Table 1, run no. 3) was synthesized using 0.390 g
(1.85 mmol) of 9,9-dimethylxanthene, 2.75 ml
(4.67 mmol) of a 1.69 M solution of butyllithium in
petroleum ether, and 0.7 ml (0.54 g, 4.63 mmol) of
TMEDA. Bis[3,5-bis(trifluoromethyl)phenyl]chloro-
phosphine [21], 2.28 g (4.62 mmol) was added at
65 C. White crystals, yield 755 mg (30%).
9,9-Dimethyl-4,5-bis[bis(4-methoxyphenyl)phos-
phino]xanthene (p-MeOXantphos). A 1.69 M solu-
tion of butyllithium in petroleum ether (bp 65 68 C),
3.8 ml (6.42 mmol) was added with stirring at room
temperature under argon to a solution of 0.545 g
(2.591 mmol) of 9,9-dimethylxanthene and 0.77 g
(1 ml, 6.62 mmol) of TMEDA. The mixture turned
dark red. It was heated for 50 min under reflux (on
a water bath) and cooled to 0 C, and a solution of
1.80 g (6.44 mmol) of chlorobis(4-methoxyphenyl)-
phosphine [21] in 8 ml of THF was added dropwise
with stirring over a period of 20 min. The mixture
was allowed to warm up to room temperature, stirred
for 14 h, diluted with 80 ml of methylene chloride,
washed with two portions of water, dried over
MgSO4, and evaporated. The residue was washed with
petroleum ether and subjected to column chromatog-
raphy on silica gel (40 63 m, Fluka), using in
succession benzene, benzene CH2Cl2, and CH2Cl2 as
eluent. The white solid thus isolated was additionally
purified by reprecipitation from methylene chloride
with petroleum ether. Yield 630 mg (35%), white
9,9-Dimethyl-4,5-bis[bis(pentafluorophenyl)-
phosphino]xanthene (FluoroXantphos) (Table 1,
run no. 5). The synthesis was performed using 0.425 g
(2.02 mmol) of 9,9-dimethylxanthene, 2.8 ml
(5.04 mmol) of a 1.8 M solution of butyllithium in
petroleum ether, and 0.76 ml (0.58 g, 5.03 mmol)
of TMEDA. Chlorobis(pentafluorophenyl)phosphine
[22], 2 g (5 mmol) was added at 90 C over a period
of 10 min, the mixture was allowed to warm up to
room temperature, stirred for 16 h, diluted with
120 ml of chloroform, washed with three portions of
a solution of potassium chloride, dried over MgSO4,
and evaporated. The residue was subjected to column
chromatography using as eluent ethyl acetate petro-
leum ether (bp 65 68 C), first 1:40 and then 1:20.
The product was additionally purified by recrystalliza-
tion from methanol. White crystals, yield 234 mg
1
crystals, mp 219 222 C. H NMR spectrum (CDCl3),
, ppm: 7.38 d (2H, J = 7.6 Hz), 7.08 m (8H), 6.94 t
(2H, J = 7.6 Hz), 6.74 d (8H, J = 8.4 Hz), 6.53 d
(2H, J = 7.7 Hz), 3.78 s (12H), 1.63 s (6H). 31P {1H}
1
(12%), mp 227 229 C. H NMR spectrum (CDCl3),
, ppm: 7.54 d (2H, J = 7.6 Hz), 7.09 t (2H, J =
NMR spectrum (CDCl3):
20.27 ppm. Mass spec-
7.6 Hz), 6.72 m (2H), 1.70 s (6H). 31P {1H} NMR
P
trum, m/z (Irel, %): 698 (100) [M]+ . Found, %:
C 74.10; H 5.76. C43H40O5P2. Calculated, %: C 73.92;
H 5.77. The other ligands were synthesized by
a similar procedure.
spectrum (CDCl3):
58.3 ppm. 19F NMR spectrum
(CDCl3), F, ppm: P131.22 m (8F), 150.34 t (4F,
J = 20.7 Hz), 161.18 t (8F, J = 20.7 Hz). Mass
spectrum, m/z (Irel, %): 938 (5) [M]+, 923 (100) [M
CH3]. Found, %: C 49.92; H 1.41. C39H12F20OP2.
Calculated, %: C 49.90; H 1.29.
9,9-Dimethyl-4,5-bis{bis[bis(3,5-trifluoromethyl)-
phenyl]phosphino}xanthene [3,5-(CF3)2Xantphos]
(Table 1, run no. 2) was synthesized using 0.390 g
(1.85 mmol) of 9,9-dimethylxanthene, 2.75 ml
(4.67 mmol) of a 1.69 M solution of BuLi, and 0.7 ml
(0.54 g, 4.63 mmol) of TMEDA. A solution of 2.28 g
(4.62 mmol) of bis[3,5-bis(trifluoromethyl)phenyl]-
chlorophosphine [21] was added at 0 C. After approp-
riate treatment, the residue (a viscous material) was
purified by column chromatography using petroleum
ether (bp 65 68 C) diethyl ether (first 20:1 and then
10:1) as eluent. The isolated white solid was recrys-
tallized from methanol. Yield 154 mg (7%), mp 164
9,9-Dimethyl-4,5-bis(diphenylarsino)xanthene
(Xantharsine) was synthesized using 0.670 mg
(3.18 mmol) of 9,9-dimethylxanthene, 4.5 ml
(8.10 mmol) of a 1.8 M solution of butyllithium in
petroleum ether, and 1.19 ml (0.92 g, 7.9 mmol) of
TMEDA. Chloro(diphenyl)arsine, 2.1 g (7.94 mmol),
was added at 60 C over a period of 30 min. The
mixture was allowed to warm up to room temperature,
stirred for 17 h, diluted with 100 ml of methylene
chloride, washed with two portions of water, dried
over MgSO4, and evaporated. The residue was washed
with petroleum ether and recrystallized from i-PrOH
1
165 C. H NMR spectrum (CDCl3), , ppm: 7.88 s
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 39 No. 12 2003

1748
SERGEEV et al.
CHCl3 (5:1). Yield 1.116 g (52%). White crystals,
mp 209 211 C. H NMR spectrum (CDCl3), , ppm:
Table 2. The conversion with respect to the initial aryl
halide was determined by GLC.
1
7.38 d (2H, J = 7.6 Hz), 7.21 m (20H), 6.93 t (2H,
J = 7.6 Hz), 6.66 d (2H, J = 7.6 Hz), 1.63 s (6H).
13C {1H} NMR spectrum (CDCl3), C, ppm: 152.35,
139.65, 133.90, 132.34, 129.82, 128.32, 128.00,
126.35, 123.60, 34.54, 31.99. Mass spectrum, m/z
(Irel, %): 666 (100) [M]+, 651 (71) [M CH3], 589
(39) [M C6H5], 422 (22) [M CH3 Ph2As], 345
(18) [M CH3 Ph2As C6H5]. Found, %: C 69.91;
H 5.11. C39H32As2O. Calculated, %: C 70.28; H 4.84.
N,N -Di-p-chlorophenylurea. In the presence of
3,5-(CF3)2Xantphos. From 115 mg (0.6 mmol) of
p-bromochlorobenzene, 23 mg (0.36 mmol) of urea,
285 mg (0.85 mmol) of Cs2CO3, 6.2 mg (0.006 mmol)
of Pd2(dba)3 CHCl3, and 20.2 mg (0.018 mmol) of
3,5-(CF3)2Xantphos in 3 ml of dioxane we obtained
1
69 mg (81%) of a white solid. H NMR spectrum
(DMSO-d6), , ppm: 8.84 s (2H), 7.47 d (4H, J =
8.8 Hz), 7.32 d (4H, J = 8.8 Hz). Found, %: C 55.63;
H 3.62; N 9.58. C13H10Cl2N2O. Calculated, %:
C 55.54; H 3.59; N 9.96.
9,9-Dimethyl-4,5-bis[diphenylphosphino]xan-
thene (Xantphos) was synthesized by the procedure
1
reported in [20]. mp 229 230 C. H NMR spectrum
N,N -Di-p-chlorophenylurea. In the presence of
Xantphos. From 190 mg (0.99 mmol) of p-chloro-
bromobenzene, 39 mg (0.65 mmol) of urea, 450 mg
(1.38 mmol) of Cs2CO3, 20.46 mg (0.0198 mmol) of
Pd2(dba)3 CHCl3, and 32.97 mg (0.057 mmol) of
Xantphos in 3 ml of dioxane we obtained 110 mg
(79%) of a white solid which contained (according
(CDCl3), , ppm: 7.41 d (2H, J = 7.7 Hz), 7.15
7.30 m (20H), 6.96 t (2H, J = 7.7 Hz), 6.55 d (2H,
J 7.7 = Hz), 1.66 s (6H). 31P {1H} NMR spectrum
(CDCl3):
17.5 ppm.
P
9,9-Dimethyl-4,5-bis[bis(2-methylphenyl)phos-
phino]xanthene (o-TolXantphos) was synthesized
by the procedure reported in [18]. mp 229 230 C.
1H NMR spectrum (CDCl3), , ppm: 7.42 d (2H, J =
7.6 Hz), 7.20 7.06 m (8H), 7.00 6.91 m (6H), 6.67 d
(4H, J = 7.6 Hz), 6.47 d (2H, J = 7.6 Hz), 2.26 s
(12H), 1.68 s (6H). 31P {1H} NMR spectrum
1
to the H NMR and mass spectral data), 14% of
N-p-chlorophenyl-N -phenylurea. Mass spectrum, m/z
(Irel, %): 280 (10) [p-ClC6H4NHC(O)NHC6H4Cl-p]+ ,
246 (1.7) [p-ClC6H4NHC(O)NHC6H5]+ , 153 (23)
[p-ClC6H4NCO]+ , 127 (100) [p-ClC6H4NH2]+ .
1H NMR spectrum (DMSO-d6), , ppm: 8.84 s (2H),
7.47 d (4H, J = 8.9 Hz), 7.32 d (4H, J = 8.9 Hz) [11].
Recrystallization from ethanol gave 89 mg (64%) of
a solid with mp >300 C; published data: mp 292
294 C [23], 303 305 C [24], 318 C [25].
(CDCl3):
32.43 ppm.
P
General procedure for arylation of urea.
A reactor was filled with argon and charged with
0.65 mmol of urea, 1.4 mmol of Cs2CO3, 0.5 2 mol %
2
(0.5 2 10 mmol) of Pd2(dba)3 CHCl3, and 1.5
2
6 mol % (1.5 6 10 mmol) of 3,5-(CF3)2Xantphos
N,N -Di-o-chlorophenylurea. In the presence of
3,5-(CF3)2Xantphos. From 114 mg (0.59 mmol) of
o-bromochlorobenzene, 21 mg (0.35 mmol) of urea,
285 mg (0.85 mmol) of Cs2CO3, 3.1 mg (0.003 mmol)
of Pd2(dba)3 CHCl3, and 10.1 mg (0.009 mmol) of
3,5-(CF3)2Xantphos in 3 ml of dioxane we obtained
or Xantphos, and a solution of 1 mmol of aryl
bromide and 0.2 mmol of 1,2,4,5-tetramethylbenzene
(internal standard) in 4 ml of dioxane saturated with
argon were added in a stream of argon. The mixture
was degassed by triple freezing evacuation defrosting
procedure, and the reactor was filled with argon. The
mixture was stirred at 100 C. The progress of the
reaction was monitored by GLC and TLC (Silufol
UV-254 plates). When the reaction was complete,
the mixture was diluted with 30 ml of ethyl acetate
and filtered. The filtrate was evaporated, and the
residue was subjected to chromatography on silica gel
(40 100 m) using ethyl acetate petroleum ether
(bp 65 68 C) as eluent.
1
77 mg (81%) of a white solid. H NMR spectrum
(DMSO-d6), , ppm: 9.03 s (2H), 8.07 d (2H, J =
8.0 Hz), 7.47 d (2H, J = 8.0 Hz), 7.30 d.d (2H, J =
7.7, 8.0 Hz), 7.06 d.d (2H, J = 7.7, 8.0 Hz). Found,
%: C 55.53; H 3.53; N 9.75. C13H10Cl2N2O. Calcu-
lated, %: C 55.54; H 3.59; N 9.96.
N,N -Di-o-chlorophenylurea. In the presence of
Xantphos. From 191 mg (1 mmol) of o-bromochloro-
benzene, 36 mg (0.6 mmol) of urea, 460 mg
(1.41 mmol) of Cs2CO3, 15.5 mg (0.015 mmol) of
Pd2(dba)3 CHCl3, and 26.1 mg (0.045 mmol) of
3,5-(CF3)2Xantphos in 4 ml of dioxane we obtained
80 mg (57%) of N,N -di-o-chlorophenylurea as a pale
The ligands were varied following the above proce-
dure for arylation of urea; 0.6 mmol of p-bromo-
toluene, 0.36 mmol of urea, 0.84 mmol of Cs2CO3,
2
1.2 10
mmol of Pd2(dba)3 CHCl3 (4 mol %
2
1
of Pd), 3.6 10 mmol of ligand, and 15 mg of
1,2,4,5-tetramethylbenzene (internal standard) in 3 ml
of dioxane were used. The mixture was heated with
stirring under argon over a period indicated in
yellow solid. H NMR spectrum (DMSO-d6), , ppm:
9.03 s (2H), 8.07 d (2H, J = 8.0 Hz), 7.47 d (2H, J =
8.0 Hz), 7.30 d.d (2H, J = 7.7, 8.0 Hz), 7.06 d.d
(2H, J = 7.7, 8.0 Hz). Also, 41 mg (35%) of o,o -di-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 39 No. 12 2003

VARIATION OF XANTPHOS-BASED LIGANDS
1749
chlorodiphenylamine was isolated as a colorless oily
substance. H NMR spectrum (acetone-d6), , ppm:
7.44 7.48 m (2H), 7.22 7.29 m (4H), 6.97 7.20 m
(2H), 6.71 s (1H).
N,N -Di-o-tolylurea. The reaction was performed
with 257 mg (1.5 mmol) of o-bromotoluene, 54 mg
(0.9 mmol) of urea, 680 mg (2.08 mmol) of Cs2CO3,
7.8 mg (0.0075 mmol) of Pd2(dba)3 CHCl3, and
25.3 mg (0.00225 mmol) of 3,5-(CF3)2Xantphos in
3 ml of dioxane. The light grey solid was filtered off
and dissolved in DMF, the solution was filtered, and
the product was precipitated with water. Yield 177 mg
1
N,N -Di-p-tolylurea. In the presence of 3,5-(CF3)2-
Xantphos. From 102.9 mg (0.601 mmol) of p-bromo-
toluene, 22 mg (0.36 mmol) of urea, 280 mg
(0.86 mmol) Cs2CO3, 12.6 mg (0.0122 mmol) of
Pd2(dba)3 CHCl3, and 40.4 mg (0.036 mmol) of
3,5-(CF3)2Xantphos in 3 ml of dioxane we obtained
1
(98%). White solid. H NMR spectrum (DMSO-d6),
, ppm: 8.28 s (2H), 7.79 d (2H, J = 8.0 Hz), 7.17 d
(2J, J = 7.5 Hz), 7.13 d.d (2H, J = 7.5, 8.0 Hz), 6.94 t
(2H, J = 7.5 Hz), 2.26 s (6H). Found, %: C 75.1;
H 6.67; N 11.68. C15H16N2O. Calculated, %: C 74.97;
H 6.71; N 11.66.
1
44 mg (61%) of a white solid. H NMR spectrum
(acetone-d6), , ppm: 8.02 s (2H), 6.83 d (4H, J =
8.3 Hz), 6.62 d (4H, J = 8.3 Hz), 2.87 s (6H). Found,
%: C 74.79; H 6.84; N 11.61. C15H16N2O. Calculated,
%: C 74.97; H 6.71; N 11.66. Also, 8.4 mg of
N-p-tolyl-N -[3,5-bis(trifluoromethyl)phenyl]urea
was isolated as by-product. 1H NMR spectrum
(acetone-d6), , ppm (J, Hz): 8.71 s (1H), 8.27 s (1H),
8.19 s (2H), 7.58 s (1H), 7.41 d (2H, J = 8.1), 7.11 d
(2H, J = 8.1), 2.27 s (3H). 19F {1H} NMR spectrum
Reaction of urea with o-bromotoluene in the
presence of Xantphos. From 171 mg (1.0 mmol) of
o-bromotoluene, 36 mg (0.6 mmol) of urea, 480 mg
(1.5 mmol) of Cs2CO3, 20.6 mg (0.02 mmol) of
Pd2(dba)3 CHCl3, and 35.2 mg (0.06 mmol) of
Xantphos in 4 ml of dioxane we obtained 77.2 mg
1
(acetone-d6):
61.9 ppm.
(77%) of di-o-tolylamine as a white solid. H NMR
F
Reaction of urea with p-bromotoluene in the
presence of Xantphos. From 102 mg (0.60 mmol) of
p-bromotoluene, 24 mg (0.40 mmol) of urea, 275 mg
(0.84 mmol) of Cs2CO3, 12.8 mg (0.0124 mmol) of
Pd2(dba)3 CHCl3, and 21.05 mg (0.0364 mmol) of
Xantphos in 2.5 ml of dioxane we obtained 16 mg
(22%) of a light brown solid containing N,N -di-
phenylurea, N-p-tolyl-N -phenylurea, and N,N -di-p-
tolylurea at a ratio of 5.2:10.0:6.8 (calculated from
the intensities of amide proton signals; their chemical
shifts were in agreement with published data [26]).
1H NMR spectrum (DMSO-d6), , ppm: 8.65 s
[PhNHC(O)NHPh], 8.60 s [PhNHC(O)NHTol-p),
8.54 s [PhNHC(O)NHTol-p], 8.48 s [p-TolNHC(O)-
NHTol-p], 8.40 8.47 m, 7.29 7.35 m, 7.23 7.29 m,
7.04 7.10 m, 6.92 6.99 m. Mass spectrum, m/z
(Irel, %): 240 (54) [p-TolNHC(O)NHTol-p]+ , 226
(72) [PhNHC(O)NHTol-p]+ , 212 (28) [PhNHC(O)-
NHPh]+ , 133 (23) [p-TolNCO]+ , 119 (23)
[PhNCO]+ , 107 (100) [p-TolNH2]+ , 93 (98)
[PhNH2]+ .
N,N -Di-m-tolylurea. From 102 mg (0.600 mmol)
of m-bromotoluene, 22 mg (0.36 mmol) of urea,
2 8 0 m g (0 . 8 6 mmol) of Cs2CO3, 6. 4 mg
(0.0062 mmol) of Pd2(dba)3 CHCl3 and 20.2 mg
(0.0018 mmol) of 3,5-(CF3)2Xantphos in 3 ml of
dioxane we obtained 72 mg (71%) of a white solid.
1H NMR spectrum (DMSO-d6), , ppm: 8.55 s (2H),
7.29 s (2H), 7.21 d (2H, J = 8.1 Hz), 7.14 d.d (2H,
J = 7.4, 8.1 Hz), 6.87 d (2H, J = 7.4 Hz), 2.27 s (3H).
Found, %: C 74.71; H 6.77; N 11.24. C15H16N2O.
Calculated, %: C 74.97; H 6.71; N 11.66.
spectrum (acetone-d6), , ppm: 7.17 d (2H, J =
7.4 Hz), 7.07 t (2H, J = 7.8 Hz), 6.86 t (2H, J =
7.4 Hz), 6.81 d (2H, J = 7.8 Hz), 6.06 s (1H), 2.23 s
(6H). According to the H NMR data, the product
contained about 7% of impurities.
1
N,N -Di(o-methoxyphenyl)urea. From 112 mg
(0.6 mmol) of o-bromoanisole, 22 mg (0.36 mmol)
of urea, 270 mg (0.83 mmol) of Cs2CO3, 9.7 mg
(0.0093 mmol) of Pd2(dba)3 CHCl3, and 30.3 mg
(0.027 mmol) of 3,5-(CF3)2Xantphos in 3 ml of
dioxane we obtained 65 mg (80%) of a white solid.
1H NMR spectrum (DMSO-d6), , ppm: 8.80 s (2H),
8.09 d (2H, J = 7.9 Hz), 6.99 d (2H, J = 7.9 Hz),
6.93 d.d (2H, J = 7.5, 7.8 Hz), 6.87 d.d (2H, J = 7.5,
7.8 Hz), 3.87 s (6H). Found, %: C 66.05; H 6.07;
N 9.82. C15H16N2O3. Calculated, %: C 66.16; H 5.92;
N 10.29.
General procedure for arylation of phenylurea.
A reactor was filled with argon and charged with
0.6 mmol of phenylurea, 0.84 mmol of Cs2CO3,
1 2 mol % of Pd2(dba)3 CHCl3, and 3 6 mol % of
Xantphos or 3,5-(CF3)2Xantphos, and a solution of
0.6 mmol of aryl bromide in 3 ml of dioxane saturated
with argon was added. The mixture was degassed by
triple freezing evacuation defrosting procedure, and
the reactor was filled with argon. The mixture was
stirred at 100 C under argon, and the progress of
the reaction was monitored by GLC and TLC (Silufol
UV-254). When the reaction was complete, the mix-
ture was cooled to room temperature, diluted with
30 ml of ethyl acetate, filtered, and evaporated. The
residue was purified by chromatography on silica gel
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 39 No. 12 2003

1750
SERGEEV et al.
(40 63 m, Fluka) using ethyl acetate petroleum
ether (bp 65 68 C) as eluent.
Tol-p], 8.55 c [PhNHC(O)NHTol-p], 7.39 7.53 m,
7.33 d (J = 8.2 Hz), 7.22 7.30 m, 7.07 d (J = 8.2 Hz),
6.91 7.00 m, 2.24 s.
N-p-Chlorophenyl-N -phenylurea. From 96 mg
(0.5 mmol) of p-bromochlorobenzene, 68 mg
(0.50 mmol) of phenylurea, 230 mg (0.70 mmol) of
Cs2CO3, 5.3 mg (0.0051 mmol) of Pd2(dba)3 CHCl3,
and 17.1 mg (0.00152 mmol) of 3,5-(CF3)2Xantphos
in 2.5 ml of dioxane we obtained 105 mg of a white
N-Phenyl-N -m-tolylurea. From 103 mg
(0.60 mmol) of m-bromotoluene, 81 mg (0.59 mmol)
of phenylurea, 280 mg (0.86 mmol) of Cs2CO3,
7.74 mg (0.0075 mmol) of Pd2(dba)3 CHCl3, and
25.2 mg (0.0224 mmol) of 3,5-(CF3)2Xantphos in
3 ml of dioxane we obtained 109 mg (81%) of a white
1
solid. H NMR spectrum (DMSO-d6), , ppm: 8.80 s
1
(1H), 8.69 s (1H), 7.48 d (2H, J = 8.6 Hz), 7.44 d
(2H, J = 8.0 Hz), 7.31 d (2H, J = 8.6 Hz), 7.27 t
(2H, J = 7.4, J = 8.0 Hz), 6.97 d (1H, J = 7.4 Hz).
solid. H NMR spectrum (DMSO-d6), , ppm: 8.63 s
(1H), 8.57 s (1H), 7.45 d (2H, J = 8.0 Hz), 7.18
7.33 m (4H), 7.15 t (1H, J = 7.7 Hz), 6.96 t (1H,
J = 7.4 Hz), 6.78 d (1H, J = 7.4 Hz), 2.27 s (3H).
Found, %: C 74.02; H 6.42; N 11.44. C14H14N2O.
Calculated, %: C 74.31; H 6.24; N 12.38.
1
According to the H NMR data, the product also con-
tained 8% of N,N -diphenylurea and 8% of N,N -di-
p-chlorophenylurea (calculated from the intensities of
the amide proton signals [11]).
N-Phenyl-N -o-tolylurea. From 104 mg
(0.61 mmol) of o-bromotoluene, 81 mg (0.59 mmol)
of phenylurea, 270 mg (0.83 mmol) of Cs2CO3,
7.8 mg (0.0075 mmol) of Pd2(dba)3 CHCl3, and
25.5 mg (0.0227 mmol) of 3,5-(CF3)2Xantphos in
3 ml of dioxane we obtained 128 mg (95%) of a white
N-o-Chlorophenyl-N -phenylurea. From 95 mg
(0.49 mmol) of o-bromochlorobenzene, 68 mg
(0.50 mmol) of phenylurea, 230 mg (0.70 mmol) of
Cs2CO3, 2.6 mg (0.0025 mmol) of Pd2(dba)3 CHCl3,
and 8.6 mg (0.0076 mmol) of 3,5-(CF3)2Xantphos in
2.5 ml dioxane we obtained 116 mg (95%) of a white
1
solid. H NMR spectrum (DMSO-d6), , ppm: 9.01 s
1
solid. H NMR spectrum (DMSO-d6), , ppm: 9.39 s
(1H), 7.91 s (1H), 7.83 d (1H, J = 8.0 Hz), 7.45 d
(2H, J = 7.7, 8.3 Hz), 7.27 t (2H, J = 8.0 Hz), 7.17 d
(1H, J = 7.5 Hz), 7.12 d (1H, J = 7.7 Hz), 6.6 d
(J = 7.4 Hz), 6.93 d (J = 7.4 Hz). Found, %: C 74.24;
H 6.42; N 12.36. C14H14N2O. Calculated, %: C 74.31;
H 6.24; N 12.38.
(1H), 8.27 s (1H), 8.16 d (1H, J = 8.2 Hz), 7.4
7.53 m (3H), 7.29 d.d (4H, J = 7.4, 8.2 Hz), 6.94
7.08 m (3H). Found, %: C 63.14; H 4.56; N 11.18.
C13H11ClN2O. Calculated, %: C 63.29; H 4.49;
N 11.36.
N-Phenyl-N -p-tolylurea. From 106 mg
(0.49 mmol) of p-bromotoluene, 82 mg (0.6 mmol)
of phenylurea, 270 mg (0.83 mmol) of Cs2CO3,
10.9 mg (0.0025 mmol) of Pd2(dba)3 CHCl3, and
35.9 mg (0.032 mmol) of 3,5-(CF3)2Xantphos in 3 ml
of dioxane we obtained 108 mg (80%) of a white
N-(o-Methoxyphenyl)-N-phenylurea. From 94 mg
(0.50 mmol) of o-bromoanisole, 69 mg (0.50 mmol)
of phenylurea, 225 mg (0.69 mmol) of Cs2CO3,
11 mg (0.0106 mmol) of Pd2(dba)3 CHCl3, and
33.9 mg (0.0302 mmol) of 3,5-(CF3)2Xantphos in
2.5 ml of dioxane we obtained 111 mg (91%) of
1
1
solid. H NMR spectrum (DMSO-d6), , ppm: 8.86 s
a white solid. H NMR spectrum (DMSO-d6), , ppm:
(1H), 8.80 s (1H), 7.69 d (2H, J = 8.0), 7.59 d (2H,
J = 8.0 Hz), 7.52 t (2H, J = 7.7 Hz), 7.34 d (2H, J =
8.0 Hz), 7.21 t (1H, J = 7.4 Hz), 2.76 s (3H). Found,
%: C 74.10; H 6.34; N 12.17. C14H14N2O. Calculated,
%: C 74.31; H 6.24; N 12.38.
9.3 s (1H), 8.22 s (1H), 8.12 d (1H, J = 7.8 Hz),
7.45 d (2H, J = 8.0 Hz), 7.27 d.d (2H, J = 7.8,
8.0 Hz), 6.85 7.04 m (4H), 3.87 s (3H). Found, %:
C 69.24; H 5.85; N 11.27. C14H14N2O2. Calculated,
%: C 69.41; H 5.82; N 11.56.
Reaction of p-bromotoluene with phenylurea in
the presence of Xantphos. From 104 mg (0.60 mmol)
of p-bromotoluene, 82 mg (0.6 mmol) of phenylurea,
285 mg (0. 87 mmol) of Cs2CO3, 12.6 mg
(0.0025 mmol) of Pd2(dba)3 CHCl3, and 21.3 mg
(0.0368 mmol) of Xantphos in 3 ml of dioxane
we obtained 75 mg of a light brown solid consisting
of N-phenyl-N -p-tolylurea and N,N -diphenylurea at
a ratio of 39:17 (calculated from the intensity ratio
Reaction of o-bromotoluene with phenylurea
in the presence of Xantphos. From 102 mg
(0.59 mmol) of o-bromotoluene, 80 mg (0.59 mmol)
of phenylurea, 270 mg (0.83 mmol) of Cs2CO3,
12.7 mg (0.0122 mmol) of Pd2(dba)3 CHCl3, and
21.2 mg (0.0366 mmol) of Xantphos in 3 ml of
dioxane we obtained 40 mg of a colorless solid con-
sisting of N-phenyl-N -o-tolylurea and N,N -diphenyl-
urea at a ratio of 19:10 (calculated from the intensity
ratio of the amide proton signals in the 1H NMR spec-
trum; the chemical shifts were consistent with those
1
of the amide proton signals in the H NMR spectrum;
the chemical shifts were consistent with those given
1
1
in [11, 26]). H NMR spectrum (DMSO-d6), , ppm:
given in [11, 26]). H NMR spectrum (DMSO-d6),
8.66 s [PhNHC(O)NHPh], 8.61 s [PhNHC(O)NH-
, ppm: 9.01 s [PhNHC(O)NHTol-o], 8.66 s [PhNH-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 39 No. 12 2003

VARIATION OF XANTPHOS-BASED LIGANDS
1751
C(O)NHPh], 7.91 s [PhNHC(O)NHTol], 7.84 d (J =
7.4 Hz), 7.42 7.50 m, 7.33 d.d (J = 7.4, 8.6 Hz),
7.27 m, 7.10 7.20 m, 6.90 7.00 m, 2.24 s.
(0.71 mmol) of t-BuONa, 12.4 mg (0.012 mmol) of
Pd2(dba)3 CHCl3, and 34.3 mg (0.0306 mmol) of
3,5-(CF3)2Xantphos in 2.5 ml of dioxane we obtained
26 mg (21%) of N-(p-methoxyphenyl)-p-methylbenz-
amide as a white solid.
This study was financially supported by the Rus-
sian Foundation for Basic Research (project nos. 00-
15-97406, 01-03-32518).
Arylation of p-methylbenzamide with p-bromo-
anisole. A reactor was filled with argon and charged
with 0.4 mmol of p-methylbenzamide, 0.56 mmol of
Cs2CO3, 4 mol % of Pd2(dba)3 CHCl3, and 6 mol %
of 3,5-(CF3)2Xantphos, and a solution of 0.4 mmol of
p-bromoanisole in 3 ml of dioxane saturated with
argon was added. The mixture was degassed by
evacuation, the reactor was filled with argon, and
the mixture was stirred at 100 C under argon, the
progress of the reaction being monitored by GLC and
TLC (Silufol UV-254). When the reaction was com-
plete, the mixture was cooled to room temperature,
diluted with 30 ml of ethyl acetate, filtered, and
evaporated. The residue was subjected to chromatog-
raphy on silica gel (40 63 m, Fluka), using ethyl
acetate petroleum ether (bp 65 68 C) as eluent.
REFERENCES
1. Vishnyakova, T.P., Golubeva, I.A., and Glebo-
va, E.V. Usp. Khim., 1985, vol. 54, p. 429; Vyshnya-
kova, T.P., Golubeva, I.A., and Glebova, E.V., Russ.
Chem. Rev. (Engl. Transl.), 1985, vol. 54, p. 249.
2. Schmidtchen, F.P. and Berger, M., Chem. Rev. 1997,
vol. 97, p. 1609.
3. Okaniwa, M., Takeuchi, K., Asai, M., and Ueda, M.,
Macromolecules, 2002, vol. 35, p. 6224; Oka-
niwa, M., Takeuchi K., Asai, M., and Ueda, M.,
Macromolecules, 2002, vol. 35, p. 6232.
Arylation of p-methylbenzamide with p-bromo-
anisole in the presence of Cs2CO3. From 54.4 mg
(0.4 mmol) of p-methylbenzamide, 73.2 mmol
(0.39 mmol) of p-bromoanisole, 185 mg (0.56 mmol)
of Cs2CO3, 8.3 mg (0.008 mmol) of Pd2(dba)3
CHCl3, and 27.2 mg (0.0243 mmol) of 3,5-(CF3)2-
Xantphos in 2 ml of dioxane we obtained 35 mg
(37%) of N-p-methoxyphenyl-p-methylbenzamide as
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1
a white solid. H NMR spectrum (DMSO-d6), , ppm:
9.37 s (1H), 7.88 d (2H, J = 8.3 Hz), 7.74 d (2H, J =
9.2 Hz), 7.29 d (2H, J = 8.3 Hz), 6.90 d (2H, J =
9.2 Hz), 3.78 s (3H), 2.38 s (3H). Found, %: C 74.24;
H 6.12; N 6.07. C15H15NO2. Calculated, %: C 74.59;
H 6.22; N 5.80. In addition, 25 mg (18%) of N-[3,5-
bis(trifluoromethyl)phenyl]-p-methylbenzamide was
isolated as a light yellow solid, mp 159 160 C.
1H NMR spectrum (DMSO-d6), , ppm: 10.03 s (1H),
8.56 s (2H), 7.97 d (2H, J = 8.3 Hz), 7.74 s (1H),
7.36 d (2H, J = 8.3 Hz), 2.41 s (3H).
Arylation of p-methylbenzamide with p-bromo-
anisole in the presence of K3PO4. From 92.3 mg
(0.49 mmol) of p-methylbenzamide, 67.1 mmol
(0.49 mmol) of p-bromoanisole, 160 mg (0.75 mmol)
of K3PO4, 10.3 mg (0.01 mmol) of Pd2(dba)3 CHCl3,
and 27.2 mg (0.0299 mmol) of 3,5-(CF3)2Xantphos
in 2.5 ml of dioxane we obtained 41 mg (35%) of
N-(p-methoxyphenyl)-p-methylbenzamide as a white
solid. In addition, 39 mg (19%) of N-[3,5-bis(tri-
fluoromethyl)phenyl]-p-methylbenzamide was isolated
as a light yellow solid.
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From 94 mg (0.50 mmol) of p-methylbenzamide,
67.3 mmol (0.49 mmol) of p-bromoanisole, 68 mg
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