Palladium-catalyzed arylation of ureas

Article abstract of DOI:10.1023/A:1016503307552

Urea arylation with aryl halides in the presence of catalyst precursor Pd₂dba₃-CHCl₃/Xantphos and Cs ₂CO₃ in dioxane at 100°C affords symmetrical N,N′-diarylureas in 64-92% yield. With the same cataly

Full text of DOI:10.1023/A:1016503307552

Russian Journal of Organic Chemistry, Vol. 38, No. 4, 2002, pp. 538 545. Translated from Zhurnal Organicheskoi Khimii, Vol. 38, No. 4, 2002,
pp. 563 570.
Original Russian Text Copyright
2002 by Artamkina, Sergeev, Beletskaya.
Palladium-catalyzed Arylation of Ureas
G. A. Artamkina, A. G. Sergeev, and I. P. Beletskaya
Lomonosov Moscow State University, Moscow, 119899 Russia
Received July 10, 2001
Abstract Urea arylation with aryl halides in the presence of catalyst precursor Pd2dba3 CHCl3/Xantphos
and Cs2CO3 in dioxane at 100 C affords symmetrical N,N -diarylureas in 64 92% yield. With the same
catalytic system the reaction between N-phenylurea and aryl bromides containing electron-withdrawing
substituents in the para-position provided N-aryl-N -phenylureas in 64 91% yields.
N,N -Diarylureas found wide application in
agriculture [1, 2], synthesis of pharmaceuticals [2],
as receptors for binding anions [3] etc. The most
common preparation method for arylureas consists in
reacting anilines with highly toxic compounds
(phosgene, aryl isocyanates, or carbon monoxide) [2].
As alternative to these classical procedures may be
arylation of urea with aryl halides in the presence of
transition metal complexes. Similar reactions found
amides and carbamates [8]. Also were described
several cases of intermolecular N-arylation of lactams
[9] and carbamates [10]. And only quite recently was
preformed an efficient arylation of amides, sulfon-
amides, and lactams with the use of a catalytic system
Pd(OAc)2/Xantphos [11]. As to ureas, no attempts of
its catalytic arylation have been performed up till now.
In order to select an optimal ligand for catalytic
arylation of urea we carried out a number of reactions
between p-bromobenzotrifluoride with urea at molar
ratio 1: 2 using 1 mol% (2 mol% of Pd) of Pd2dba3
CHCl3 and 3 mol% of ligand L in the presence of
Cs2CO3 as base in dioxane at 100 C (Table 1).
recently wide application for building up a CAr
N
bond [4. 5]. Among these are obviously interesting
reactions with copper-containing catalysts that
provide a possibility of arylation both of amines,
amides and imides. However these reactions usually
require stringent conditions and in some cases equi-
molar or more amounts of copper, and the yields
often are low [6].
As seen from Table 1, the most efficient ligand
was Xantphos: in this case the reaction completed in
4 h and afforded as the main product N,N -di(p-tri-
fluoromethylphenyl)urea in 89% yield, and the cor-
responding monoarylurea formed in a small amount
(5%). The prevailing formation of diarylurea in this
reaction can result from low solubility of urea in
dioxane. Tri(o-tolyl)phosphine was inefficient in this
reaction. At the use of bis(2,2 -diphenylphosphino)-
The most efficient catalysts for amines arylation
are now palladium complexes [5, 7]. However under
these conditions remains uncertain the arylation of
compounds with amino group of low basicity, e.g.,
amides or sulfonamides. The first examples of amides
arylation consisted in intramolecular cyclization of
Table 1. Variation of ligands L
Ligand
BINAP
DPPF
DPE-Phos
Xantphos
Time, h
Conversion, %
(yield, %)
18
0
18
50
(17)
18
58
(22)
18
48
(17)
4
100
89
1070-4280/01/3804-538$27.00 2002 MAIK Nauka/Interperiodica

PALLADIUM-CATALYZED ARYLATION OF UREAS
Table 2. Palladium-catalyzed arylation of urea
539
Run no.
Arylhalogenides Pd, mol% Time, h
Product
Yield, %
1
2
4
89
2
3
4
1
1
1
6.5
4
92
86
75
4
5
1
2.5
89
6
7
4
4
10
10
64
70
8
9
4
4
13
20
74
22
di-1,1 -naphthyl (BINAP) or DPPF and DPE-Phos
the reaction did not go to completion, the yield of
diarylurea was low, and arose a significant amount of
di(p-trifluoromethylphenyl)amine (18 29%) (Table1).
With Xantphos as ligand we performed a number
of urea arylation using the latter in slight excess
(Table 2).
Reactions with aryl bromides having electron-with-
drawing groups readily occur in the presence of
1 2 mol% of Pd furnishing N,N -diarylureas in high
yield (Table 2, runs nos. 1 5). The reaction with aryl
chlorides proceeds with greater difficulty. For
instance, with p-chlorobenzotrifluoride the conversion
was only 25% in 15 h at the use of 2 mol% of the
catalyst.
It should be specially mentioned that in reaction of
urea with o-iodonitrobenzene the main reaction
product was di(o-nitrophenyl)amine:
Apparently the arising N,N -di(o-nitrophenyl)urea
is cleaved by the base yielding o-nitroaniline that
R= CO2Et, CF3, CN, PhC(O), NO2, Cl, H; X= Br, I.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 4 2002

540
ARTAMKINA et al.
sisted of N,N-diphenyl, N-(p-tolyl)-N -phenyl- and
N,N -di(p-tolyl)ureas in molar ratio 5.2 : 10: 6.8 in an
overall yield 22%. The N-phenylated products arise
from the exchange of the aryl group bonded to pallad-
ium with the phenyl group of phosphine followed by
reductive elimination. This process is often observed
in the reactions of cross-coupling and amination by
aryl halides containing electron-donor substituents
[14]. The considerable content of phenyl groups in
the arylation product obtained from urea and p-bromo-
toluene corresponds to very high extent of phenyl
group migration from Xantphos (85%).
further is arylated into the corresponding diaryl-
amine:
Note that the corresponding N,N -di(p-nitro-
phenyl)urea is stable under reaction conditions
(Table 2, run no. 4). We observed formation of di-
arylamines also in reactions with urea of pentafluoro-
pyridine and octafluorotoluene in DMF in the
presence of CsF as a base:
We also demonstrated that the use of XANTphos
as ligand provided a possibility of catalytic arylation
of phenylurea and opens an easy and efficient way of
synthesis of unsymmetrical diarylureas (Table 3).
These reactions proceeded as SNAr processes and
did not require any catalyst. In the literature are
described similar reactions with hexafluorobenzene
[12] and pentafluoropyridine [13] in the presence of
a stronger base (NaH). However the heating of o-iodo-
nitrobenzene with urea an Cs2CO3 in dioxane for
1.5 h did not give rise to notable amounts of products.
Catalyzed reactions with weakly activated or
nonactivated aryl halides resulted in lower yields of
the target product and required more catalyst (up to
4 mol%) (Table 2, runs nos. 6 8). In these cases we
obtained as side products considerable amounts (12
14%) of the corresponding diarylamines. Besides the
reaction in run no. 6 was accompanied by formation
of a considerable amount of N-phenylation product,
N-phenyl-N -(p-chlorophenyl)urea. With p-bromo-
toluene even at 4 mol% of the catalyst the reaction
stopped at conversion of 62%, and the products con-
R = CO2Et, CF3, CN, PhC(O), NO2.
The phenylurea arylation with ethyl p-bromo-
benzoate cleanly occurred within 4h in the presence
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 4 2002

PALLADIUM-CATALYZED ARYLATION OF UREAS
Table 3. Palladium-catalyzed arylation of phenylurea
541
Run no.
Arylhalogenides Pd, mol% Time,
h
Product
Yield, %
1
2
4
58
2
3
2
2
1
1
91
90
4
5
2
2
1
80
87
1.5
6
2
1
64
of 0.5 mol% of the catalyst and resulted in unsym-
metrical N,N -diarylurea in a moderate yield. The
reaction was complicated by formation of sym-
metrical ureas, N,N -diphenylurea and N,N -di(p-
ethoxycarbonylphenyl)urea. We showed that sym-
metrical diarylureas originated from disproportiona-
tion of the reaction product, N-(p-ethoxycarbonyl-
phenyl)-N -phenylurea, in the presence of base. Thus
the heating of N-(p-ethoxycarbonylphenyl)-N -phenyl-
urea in dioxane to 100 C for 2 h in the presence of
Cs2CO3 resulted in formation of two symmetrical
N,N -diarylureas. A longer heating (14 h) gave rise
to relatively higher yield of products of dispropor-
tionation and decomposition of diarylurea.
In the absence of a base no visible disproportiona-
tion occurred even in 6 h. The increase in catalyst
amount to 2 mol% reduced the duration of the reac-
tion and the contribution of the symmetrization
process thus considerably increasing the yield of the
target products (Table 3, runs nos. 2 6). However
reaction with p-nitrobromobenzene under these con-
ditions provided a large amount of side products, and
the desired product was obtained only in 64% yield.
EXPERIMENTAL
Cesium carbonate and fluoride were dried in a
vacuum at 150 200 C. Dioxane and DMF were
purified and dried by standard procedures. Dioxane
was stored in a vacuum over benzophenone ketyl.
Pd2dba3 CHCl3 was prepared as described in [15].
Xantphos was synthesized along procedure [16].
Aryl halides before use were recrystallized or distil-
1
led. The H and 19F NMR spectra were registered
on spectrometer Varian VXR 400 at operating
frequencies 400 and 376 MHz respectively. The
chemical shifts of protons were measured relative the
signals of the residual protons of the deuterated
solvent, in the 19F NMR spectrum the chemical shifts
were measured with respect to the signal of C6H5CF3
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 4 2002

542
ARTAMKINA et al.
(
61.96 ppm from CFCl3). IR spectra were
Xantphos in 3 ml of dioxane was obtained 88 mg
(89%) of colorless solid, mp 234 236 C (publ.:
239 C [17], 209 210 C [18]). IR spectrum (KBr
pellet), cm : 3320, 1654, 1326. H NMR spectrum
(acetone-d6), , ppm (J, Hz): 8.62 s (1H), 7.76 d
(2H, 8.6), 7.63 d (2H, 8.6). Found, %: C 52.08; H
3.07; N 7.89. C15H10F6N2O. Calculated, %: C 51.73;
H 2.89; N 8.04.
F
measured on Fourier spectrophotometer Ikar (Joint
Stock Co Mikrotekh, Russia). GLC analyses were
performed on a device RSI Instruments 910 equipped
with flame-ionization detector, capillary column
10000 0.53 mm, carrier gas nitrogen. Mass spectra
were registered on Kratos MS-30 instrument, electron
impact ionization, ionizing electrons energy 70 eV.
For compounds with melting points in disagreement
with published data or when published data showed a
significant scatter in melting points the results of
elemental analysis are presented.
1
1
N,N -Di(p-ethoxycarbonylphenyl)urea. From
139 mg (0.61 mmol) of ethyl p-bromobenzoate,
25 mg (0.42 mmol of urea, 275 mg (0.84 mmol) of
3
Cs2CO3, 3.44mg(3.3 10 mmol) of Pd2dba3 CHCl3
3
General procedure for urea arylation. Into a
reactor filled with argon was charged 0.65 mmol of
urea (2.0 mmol in run no. 1), 1.4 mmol of Cs2CO3,
0.5 2 mol% (0.5 2 10 mmol) of Pd2dba3 CHCl3,
1.5 6 mol% (1.5 6 10 mmol) of Xantphos, in an
and 5.87 mg (1.01 10 mmol) of Xantphos in 3 ml
of dioxane was obtained 93 mg (85%) of colorless
solid, mp 225 227 C (publ.: 215 C [19]). IR spec-
2
1
1
trum (KBr pellet), cm : 3336, 1714, 1691. H NMR
spectrum (DMSO-d6), , ppm(J, Hz): 9.19 s (2H),
7.89 d (4H, 8.8), 7.59 d (4H, 8.8), 4.27 q (4H, 7.0),
1.30 t (6H, 7.0). Found, %: C 64.12; H 5.93; N
7.91. C19H20N2O5. Calculated, %: C 64.04; H 5.66;
N 7.86.
2
argon flow was added 1 mmol of aryl bromide and
0.2 mmol of 1,2,4,5-tetramethylbenzene (as internal
reference) in 4 ml of dioxane saturated with argon.
The reaction mixture was degassed by evacuation,
then the reactor was filled with argon. The reaction
was carried out at 100 C while stirring. The reaction
progress was monitored by GLC and (or) TLC on
Silufol UV-254 plates. On completion of the reaction
the mixture was cooled to room temperature, and the
content of the reactor was poured into 50 ml of
saturated KCl solution. Then the products were
extracted into ethyl acetate (3...20 ml), the combined
extracts were washed with KCl solution, dried on
MgSO4, and evaporated. The residue was subjected
to chromatography on silica gel 40 100 m, using as
eluent a mixture ethyl acetate petroleum ether boil-
ing within 40 70 C.
N,N -Di(p-cyanophenyl)urea. From 119 mg
(0.65 mmol) of p-bromobenzonitrile, 24 mg
(0.4 mmol) of urea, 275 mg (0.84 mmol) of Cs2CO3,
3
3.25 mg (3.14 10 mmol) of Pd2dba3 CHCl3,
3
and 5.35 mg (9.25 10 mmol) of Xantphos in 3 ml
of dioxane was obtained 79 mg (92%) of colorless
solid mp >300 C (publ.: 240 C [19], 273 C [20],
305 C [21], 275 C [22]). IR spectrum (KBr pellet),
1
1
cm : 3380, 2215, 1735. H NMR spectrum (acetone-
d6 and DMSO-d6 mixture), , ppm (J, Hz): 9.23 s
(2H), 7.74 d (4H, 9.0), 7.69 d (4H, 9.0). Found, %:
C 68.38; H 4.02; N 21.03. C15H10N4O. Calculated,
%: C 68.69; H 3.84; N 21.36.
Ligand variation. The runs with ligand variation
were performed according to procedure for urea
arylation using 0.6 mmol of p-bromo-trifluoromethyl-
benzene, 1.2 mmol of urea, 0.84 of mmol Cs2CO3,
N,N -Di(p-nitrophenyl)urea. From 122 mg
(0. 6 mmol) of p-bromonitrobenzene, 22 mg
3
(0.37 mmol) of urea, 3.16 mg (3.06 10 mmol) of
3
2
2
Pd2dba3 CHCl3, and 5.27 mg (9.11 10 mmol) of
0.6 10 mmol of Pd2dba3CHCl3, 1.8 10 mmol
of the ligand, and 0.15 mmol of 1,2,4,5-tetramethyl-
benzene (internal reference) in 3 ml of dioxane. The
reaction mixture was heated at stirring under argon
atmosphere for the time indicated in Table 1. The
conversion of the original aryl halide was estimated
Xantphos in 3 ml of dioxane was obtained 69 mg
(75%) of yellow solid, mp >300 C (publ. 364
374 C [23]).
1
IR spectrum (KBr pellet), cm : 3369, 3342, 3322,
1
3290, 1735. H NMR spectrum (DMSO-d6), , ppm
1
by GLC or from H NMR spectrum of the reaction
(J, Hz): 9.79 s (2H), 8.22 d (4H, 9.2), 7.72 d (4H,
9.2). Found, %: C 51.81; H 3.72; N 18.65.
C13H10N4O5. Calculated, %: C 51.66; H 3.33; N
18.54.
mixture (the deuterium lock was performed on
acetone-d6 placed in the external tube).
N,N -Di(p-trifluoromethylphenyl)urea. From
129 mg (0.57 mmol) of p-bromo-trifluoromethylbenz-
N,N -Di(p-benzoylphenyl)urea. From 283 mg
(1.08 mmol) of p-bromobenzophenone, 48 mg
(0.8 mmol) of urea, 500 mg (1.53 mmol) of Cs2CO3,
ene, 61 mg (1.01 mmol of urea, 240 mg (0.74 mmol)
2
of Cs2CO3, 5.44 mg (0.53 10
mmol) of
2
2
Pd2dba3 CHCl3 and 8.2 mg (1.42 10 mmol) of
5.82 mg (0.56 10 mmol) of Pd2dba3 CHCl3, and
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 4 2002

PALLADIUM-CATALYZED ARYLATION OF UREAS
543
9.29 mg (1.61 10 2 mmol) of Xantphos in 4 ml of di- (DMSO-d6), , ppm. (J, Hz): 8.65 s (2H), 7.45 d
(4H, 8.4), 7.27 t (4H, 8.4, 7.4), 6.96 t (2H, 7.4).
oxane was obtained 206 mg (90%) of solid substance
of cream color. Reprecipitation by water from DMF
solution provided 203 mg of cream-colored crystals,
mp 298 300 C (publ. 189 C [24]). Mass spectrum,
m/z (Irel, %): 420 (4.4) [p-PhC(O)C6H4NHC(O)C6H4-
Reaction of urea with p-bromotoluene. From
102 mg (0.6 mmol) of p-bromotoluene, 24 mg
(0.4 mmol) of urea, 275 mg (0.84 mmol) of Cs2CO3,
2
12.8 mg (1.24 10 mmol) of Pd2dba3 CHCl3, and
.
.
(O)Ph-p]+ , 223 (94) [p-PhC(O)C6H4NCO]+ , 197
2
21.05 mg (3.64 10 mmol) of Xantphos in 2.5 ml
.
(100) [p-PhC(O)C6H4NH2]+ . IR spectrum (KBr
of dioxane was obtained 16 mg (22%) of light-brown
solid, consisting of N,N -diphenylurea, N-p-tolyl-N-
phenylurea, and N,N -di(p-tolyl)urea in 5.2 : 10: 6.8
ratio as calculated from the integral intensity ratio of
1
1
pellet), cm : 3332, 1637, 1699. H NMR spectrum
(DMSO-d6), , ppm (J, Hz): 9.32s (2H), 7.61 7.84m
(14H), 7.55 t (4H, 7.6). Found, %: C 77.00; H 4.49;
N 6.58. C27H20N2O3. Calculated, %: C 77.13; H
4.79; N 6.66.
1
the corresponding amide proton signals in the H NMR
spectrum (the respective chemical shifts were con-
sistent with the published values [22]). Mass spec-
trum, m/z (Irel, %): 240 (54) [p-TolNHC(O)NHTol-
N,N -Di(p-chlorophenyl)urea. From 190 mg
(0.99 mmol) of p-chlorobromobenzene, 39 mg
(0.65 mmol) of urea, 450 mg (1.38 mmol) of Cs2CO3,
.
.
p]+ , 226 (72) [PhNHC(O)NHTol-p]+ , 212 (28)
.
.
2
[PhNHC(O) NHPh]+ , 133 (23) [p-TolNCO]+
,
20.46 mg (1.98 10 mmol) of Pd2dba3 CHCl3, and
.
.
119(23)[PhNCO]+ , 107 (100)[p-TolNH2]+ , 93 (98)
2
32.97 mg (5.7 10 mmol) of Xantphos in 3 ml of
.
[PhNH2]+ . H 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.
1
dioxane was obtained 110 mg (79%) of colorless
solid substance (containing as impurity according to
1H NMR and mass spectra 14% of N-p-chloro-
phenyl-N -phenylurea). Mass spectrum, m/z (Irel, %):
.
280 (10) [p-ClC6H4NHC(O)NHC6H4Cl-p]+ , 246
.
(1.7) [p-ClC6H4NHC(O)NHC6H5)]+ , 153 (23)
Reaction of urea with o-iodonitrobenzene. From
257 mg (1.03 mmol) of o-iodonitrobenzene, 43 mg
(0.72 mmol) of urea, 490 mg (1.50 mmol) of Cs2CO3,
.
.
[p-ClC6H4NCO]+ , 127 (100) [p-ClC6H4NH2]+ .
1H NMR spectrum (DMSO-d6), , ppm(J, Hz):
8.84 s (H), 7.47 d (4H, 8.9), 7.32 d (4H, 8.9);
impurity signals: 8.80 s, 8.69 s, 7.27 t, 6.99 t. After
recrystallization from ethanol we obtained 89 mg
(64%) of solid substance, mp >300 C (publ.: 292
294 C [21], 303 305 C [25], 318 C [26]). IR spec-
2
5.77 mg (0.56 10 mmol) of Pd2dba3 CHCl3, and
2
9.13 mg (3.64 10 mmol) of Xantphos in 4 ml of
dioxane was obtained 95 mg (71%) of di(o-nitrophen-
yl)amine as orange solid substance, mp 168 170 C
(publ.: 172.1 172.5 C [27], 171 171.5 C [28]).
1H NMR spectrum (DMSO-d6), , ppm (J, Hz):
10.62 s (1H), 8.18 d.d (2H, 8.5, 1.4), 7.68 m (2H),
7.60 d.d (2H, 8.4, 1.2), 7.2 m (2H).
1
trum (KBr pellet), cm : 3299, 1633. Found,%: C
55.56; H 3.49; N 9.55. C13H10Cl2N2O. Calculated,
%: C 55.54; H 3.54; N 9.96.
General procedure for phenylurea arylation. Into
a reactor filled with argon was charged 0.6 mmol of
phenylurea 0.84 mmol of Cs2CO3, 1 mol% of
Pd2dba3 CHCl3, 3 mol% of Xantphos, in an argon
flow was added 0.6 mmol of aryl bromide in 3 ml of
dioxane saturated with argon. The reaction mixture
was degassed by evacuation, then the reactor was
filled with argon. The reaction was carried out at
100 C while stirring. The reaction progress was
monitored by TLC on Silufol UV-254 plates. On
completion of the reaction the mixture was cooled to
room temperature and diluted with ethyl acetate
(40 ml), filtered, and evaporated. The residue was
subjected to chromatography on silica gel 40 100 m,
using as eluent a mixture ethyl acetate petroleum
ether boiling within 40 70 C.
N,N -Diphenylurea (Table 2, run no. 7). From
159 mg (1.01 mmol) of bromobenzene, 43 mg
(0.72 mmol) of urea, 495 mg (1.52 mmol) of Cs2CO3,
2
20.80 mg (2.30 10 mmol) of Pd2dba3 CHCl3, and
2
34.67 mg (6.31 10 mmol) of Xantphos in 4 ml of
dioxane was obtained 75 mg (70%) of colorless solid,
mp 239 241 C (publ. 235 236 C [25]). IR spectrum
1
1
(KBr pellet), cm : 3324, 1648. H NMR spectrum
(DMSO-d6), , ppm ( J, Hz): 8.65 s (2H), 7.45 d
(4H, 8.4), 7.27 t (4H, 8.4, 7.4), 6.96 t (2H, 7.4).
N,N -Diphenylurea (Table 2, run no.8). From
204 mg (1 mmol) of iodobenzene, 43 mg (0.72mmol)
of urea, 475 mg (1.46 mmol) of Cs2CO3, 20.7 mg
2
(2 10 mmol) of Pd2dba3 CHCl3, and 34.37 mg
2
(5.94 10 mmol) of Xantphos in 4 ml of dioxane
was obtained 79 mg (70%) of brown solid, mp 238
240 C (publ. 235 236 C [25]). H NMR spectrum
N-(p-Ethoxycarbonylphenyl)-N -phenylurea.
From 143 mg (0.62 mmol) of ethyl p-bromobenzo-
1
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544
ARTAMKINA et al.
ate, 81 mg (0.59 mmol) of phenylurea, 280 mg
CHCl3, and 10.81 mg (1.87 10 2 mmol) of Xantphos
in 3 ml of dioxane was obtained 99 mg (64%) of
light-yellow solid, mp 225 227 C (publ. 213 218 C
[22], 207 220 C [23]). IR spectrum (KBr pellet),
cm : 3301, 1650, 1560, 1346. H NMR spectrum
(DMSO-d6), , ppm ( J, Hz): 9.43 s (1H), 8.92 s
(1H), 8.19 d (2H, 9.2), 8.69 d (2H, 9.2), 7.47 d (2H,
8.3), 7.30 d.d (2H, 8.3, 7.4), 7.01 t (1H, 7.4).
2
(0.86 mmol) of Cs2CO3, 6.28 mg (0.61 10 mmol)
2
of Pd2dba3 CHCl3, and 11.01 mg (1.90 10 mmol)
of Xantphos in 3 ml of dioxane was obtained 156 mg
(91%) of colorless solid, mp 168 170 C (publ.:
169 C [29], 163 C [30]). IR spectrum (KBr pellet),
1
1
1
1
cm : 3351, 3315, 3307, 1716, 1699. H NMR spec-
trum (d6 DMSO), , ppm ( J, Hz): 9.09 s (1H),
8.78 s (1H), 7.89 d (2H, 8.8), 7.59 d (2H, 8.8),
7.46 d (2H, 8.5), 7.29 d.d (2H, 8.5, 7.4), 6.99 t (1H,
7.4).
Urea arylation with pentafluoropyridine. Into a
two-neck reactor was charged 405 mg (2.68 mmol) of
CsF, 175 mg (1.03 mmol) of pentafluoropyridine,
25.6 mg (0.43 mmol) of urea, and 2.5 ml of DMF.
N-(p-Trifluoromethylphenyl)-N -phenylurea.
From 145 mg (0.62 mmol) of p-trifluoromethylbromo- The reaction mixture was degassed by evacuation and
benzene, 85 mg (0.62 mmol) of phenylurea, 285 mg
heated for 7 h to 80 C. The reaction progress was
monitored by 19F NMR spectra. On completion of the
reaction the mixture was cooled to room temperature,
and the content of the reactor was poured saturated
KCl solution. Then the products were thrice extracted
into ethyl acetate, the combined extracts were washed
with KCl solution, dried, and evaporated. The residue
was subjected to chromatography on silica gel to
afford 105 mg (65%) of bis(tetrafluoropyridyl)amine
as colorless solid, mp 148 150 C (publ.: 144 146 C
[13], 149 150 C [31]). Yield according to 19F NMR
data was 68%.
2
(0.87 mmol) of Cs2CO3, 6.47 mg (0.63 10 mmol)
2
of Pd2dba3 CHCl3, and 11.07 mg (1.91 10 mmol)
of Xantphos in 3 ml of dioxane was obtained 157 mg
(90%) of colorless solid, mp 223 225 C (publ.:
1
225 C [17]). IR spectrum (KBr pellet), cm : 3311,
1
1645, 1328. H NMR spectrum (DMSO-d6), , ppm
(J, Hz): 9.09 s (1H), 8.79 s (1H), 7.64 m (4H),
7.59 d (2H, 8.8), 7.46 d (2H, 8.3), 7.29 d.d (2H, 8.3,
7.7), 7.00 t (1H, 7.4).
N-(p-Cyanophenyl)-N -phenylurea. From
115 mg (0.63 mmol) of ethyl p-bromobenzonitrile,
82 mg (0.6mmol) of phenylurea, 285 mg (0.87mmol)
Urea arylation with octafluorotoluene. The reac-
tion was carried out as with pentafluoropyridine.
From 450 mg (2.98 mmol) of CsF, 285 mg
(1.2mmol) of octafluorotoluene, 31 mg (0.52 mmol)
of urea after 41 h of heating was separated 125 mg
(46%) of bis(4-perfluorotolyl)amine as colorless solid,
mp 73 75 C (publ.: 76 77 C [31]). Yield according
to 19F NMR data was 65%.
2
of Cs2CO3, 6.45 mg (0.623 10 mmol) of Pd2dba3
2
CHCl3, and 10.85 mg (1.877 10 mmol) of Xant-
phos in 3 ml of dioxane was obtained 115 mg (80%)
of colorless solid, mp 208 210 C (publ.: 198 C [21],
210 C [22]). IR spectrum (KBr pellet), cm 1: 3301,
1
2225, 1643, 1594, 1552, 1500. H NMR spectrum
(DMSO-d6), , ppm (J, Hz): 9.19 s, (1H), 8.85 s,
(1H), 7.73 d, (2H, 8.6), 7.62 d, (2H, 8.6), 7.45 d
(2H, 8.0), 7.29 d.d (2H, 8.0, 7.4), 7.00 t (1H, 7.4).
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