Synthesis of new unsymmetric N,N′-dipyridylurea derivatives by selenium and selenium dioxide-catalyzed reductive carbonylation of substituted nitropyridines

Article abstract of DOI:10.1016/j.tet.2003.08.035

Without using phosgene, a series of new unsymmetric N,N′ -dipyridylurea derivatives have been synthesized in moderate to good yields by the one-pot reductive carbonylation of substituted nitropyridines. These reactions utilize selenium or selenium dioxide as the catalyst, aminopyridine derivatives as co-reagents, and carbon monoxide as the carbonyl source.

Full text of DOI:10.1016/j.tet.2003.08.035

Tetrahedron 59 (2003) 8251–8256
Synthesis of new unsymmetric N,N0-dipyridylurea derivatives by
selenium and selenium dioxide-catalyzed reductive carbonylation
of substituted nitropyridines
*
Jinzhu Chen, Gang Ling and Shiwei Lu
National Engineering Research Center for Catalysis, Dalian Institute of Chemical Physics, Chinese Academy of Sciences,
161 Zhongshan Road, Dalian, Liaoning 116011, People’s Republic of China
Received 28 April 2003; revised 30 July 2003; accepted 4 August 2003
Abstract—Without using phosgene, a series of new unsymmetric N,N0-dipyridylurea derivatives have been synthesized in moderate to good
yields by the one-pot reductive carbonylation of substituted nitropyridines. These reactions utilize selenium or selenium dioxide as the
catalyst, aminopyridine derivatives as co-reagents, and carbon monoxide as the carbonyl source.
q 2003 Elsevier Ltd. All rights reserved.
1. Introduction
for synthesis of urea derivatives. However, most studies
focus only on reactions of nitrobenzene derivatives, and
little has been known of the reduction20,21 and reductive
carbonylation reactions of nitr0opyridines. In this regard, the
synthesis of unsymmetric N,N -dipyridylurea derivatives by
means of such catalytic methods is even more attractive than
that of symmetric ureas, because their conformational
behavior can be studied as the model systems for
polypeptides and proteins.22
Pyridines are important heterocyclic compounds. Many
pyridylurea derivatives containing both a peptide bond
(–CONH–) and a pyridyl group possess biological
activities and are widely used as insecticides, agrochemical
fungicides, herbicides and plant growth0 regulators.1–4
However, research concerning N,N -dipyridylurea
derivatives has mostly focused on their conformational
behavior,5,6 and the conventional method for the preparation
of pyridylurea derivatives utilizes highly toxic phosgene as
the carbonyl source.5,6 This conventional process has many
disadvantages. For example, the toxicity and corrosive
nature of phosgene and formation of hydrogen chloride as
a by-product are particularly troublesome.7,8 Accordingly,
catalytic carbonylation of organic nitro compounds has been
recently investigated by several industrial and academic
research groups.9,10 The major objective of this research is
to find a new catalytic process for synthesis of important
chemicals that avoids the use of dangerous and corrosive
phosgene. The group VIII transition metals rhodium,
ruthenium and palladium have been commonly used as
catalysts for this purpose.11,12
2. Results and discussion
2.1. Synthesis of unsymmetric N,N0-dipyridylurea
derivatives
In our previous studies,17 we reported a series of unsym-
metric phenyl ureas synthesized in a one-pot reaction
sequence that combined selenium-catalyzed oxidative
carbonylation of anilines with reductive carbonylation of
nitrobenzene under relatively mild conditions. In this
reaction, the nitrobenzene acts as both a reagent and as an
oxidant, and plays an important role in the formation of a
catalytic cycle. However, aliphatic nitro compounds did not
function as reagents but only as oxidants.
Additionally, non-transition metal elements and their oxides
such as sulfur,13,14 selenium15–17 and selenium dioxide18,19
have also been found to catalyze the synthesis of urea
derivatives. These environmentally benign reactions have
many advantages over the traditional phosgene routes used
Recently, we have found that selenium and selenium
dioxide are good catalysts for the reductive carbonylation
of substituted nitropyridines, using carbon monoxide and
aminopyridine derivatives as co-reagents. A series of new
unsymmetric N,N0-dipyridylurea derivatives 1a have been
synthesized in moderate to good yields (Table 1).
Keywords: carbonylation; reduction; selenium and compounds; ureas.
*
Corresponding author. Tel.: þ86-411-3698749; fax: þ86-411-3698749;
e-mail: lusw@dicp.ac.cn; chenjz@dicp.ac.cn
0040–4020/$ - see front matter q 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2003.08.035

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J. Chen et al. / Tetrahedron 59 (2003) 8251–8256
Table 1. The synthesis of unsymmetric N,N0-dipyridylurea derivatives
Entry
Substrates
Products
Products mp (8C)
Yield (%)a
c
d
Seb
74
SeO2
SeO2
62
1
2
178–180
173–175
77
79
83
82
67
69
3
188–189
85
4
5
178
86
85
89
88
71
74
210–212
6
7
211
/
66
0
69
0
52
0
8
228–231
220–221
198–201
70
62
67
73
65
68
59
50
51
9
10
11
12
228–229
163–166
57
69
58
72
41
58
a
Isolated yields. Reaction conditions: substrate, 10 mmol; 2-methoxyl-5-nitropyridine, 10 mmol; CO, 3.0 MPa; toluene, 10 mL; 120–1308C; 4.0 h.
b
c
d
Se, 0.5 mmol; Et3N, 10 mmol.
SeO2, 0.5 mmol; Et3N, 10 mmol.
SeO2, 0.5 mmol; Ph3P, 1.0 mmol.
It was found that reactions catalyzed by both selenium and
selenium dioxide exhibit remarkable chemoselectivity, and
the substituted nitropyridines can be converted into ureas in
the same mann0er as nitrobenzene. It is worthy to note that
symmetric N,N -dipyridylurea derivatives were not detected
in the crude reaction mixtures by HPLC analysis. This is in
contrast to the reports of mixtures of three symmetric and
ð1Þ

J. Chen et al. / Tetrahedron 59 (2003) 8251–8256
8253
Table 2. Effects of different experimental conditions on selenium and
selenium dioxide-catalyzed reaction
2.2. The carbonylation of 2-methoxy-5-nitropyridine and
2-aminopyridine
Entry
Temperature
(8C)
Catalyst
(mmol)
Base
(mmol)
Yield (%)a
Treatment of 2-methoxy-5-nitropyridine with 2-aminopyri-
dine in 1: 1 molar ratio, using either selenium or selenium
dioxide as the catalyst in the presence of carbon monoxide
led to the formation of N-(2-pyridyl)-N0-(6-methoxy-3-
pyridyl)urea 1 (Eq. (2)). Parameters such as temperature,
amount of catalyst, and organic bases were investigated
(Table 2).
Se
SeO2
1
2
3
4
5
6
7
8
110
130
150
170
130
130
130
130
130
130
130
130
130
130
130
0.5
0.5
0.5
0.5
0.01
0.05
0.1
1.0
0.5
0.5
0.5
0.5
0.5
0.5
0.5
TEAb (10)
TEA (10)
TEA (10)
TEA (10)
TEA (10)
TEA (10)
TEA (10)
TEA (10)
TEA (/)
68
74
73
70
34
59
75
78
/
67
77
75
70
30
63
77
82
/
9
10
11
12
13
14
15
TEA (30)
TPPc (1)
76
/
76
77
81
81
77
62
76
75
80
83
ð2Þ
NMPd (10)
DABCOe (10)
DBNf (10)
DBUg (10)
In the temperature range from 110 to 1708C, using either
selenium or selenium dioxide, yields of 1 increased with
temperature up to 1308C and then decreased with further
increasing the reaction temperature (Table 2, entries 1–4).
Decreasing yields at temperatures above 1308C can be
rationalized if 1 decomposed faster than carbonylation of
the remaining 2-aminopyridine. The yields of 1 also
increased with increasing catalyst loading (Table 2, entries
5–8).
a
Isolated yields. Reaction conditions: 2-methoxy-5-nitropyridine,
10 mmol; 2-aminopyridine, 10 mmol; base, 0–30 mmol; CO, 3.0 MPa;
toluene, 10 mL; 110–1708C; 4.0 h; catalyst, Se or SeO2, 0.01–1.0 mmol.
Triethylamine.
Triphenylphosphine.
N-Methylpyrrolidine.
1,4-Diazabicyclo[2,2,2]octane.
1,5-Diazabicyclo[4,3,0]non-5-ene.
1,8-Diazabicyclo[5,4,0]undec-7-ene.
b
c
d
e
f
g
unsymmetric ureas being formed when primary amines
were used as co-reagents.15,17,23 In most case, selenium
dioxide showed higher catalytic activity than selenium
under the same reaction conditions. The reason that the
catalytic activity of selenium dioxide was little higher than
that of selenium can be presumably rationalized that
selenium dioxide more readily forms the necessary reactive
intermediate.
Organic bases dramatically affect formation of the product
(Table 2, entries 9–15). Besides triethylamine, stronger
organic bases such as 1,8-diazabicyclo[5,4,0]undec-7-ene
(DBU) and 1,5-diazabicyclo[4,3,0]non-5-ene (DBN), the
tertiary amine as 1,4-diazabicyclo[2,2,2]octane (DABCO)
and the amide N-methylpyrrolidine (NMP) were all
effective in the reductive carbonylation of 2-methoxy-5-
nitropyridine with 2-aminopyridine. Interestingly, in the
presence of triphenylphosphine (Table 2, entry 11), the
selenium dioxide-catalyzed reaction afforded 1 in 62%
yield, but the selenium-catalyzed reaction did not take place
under the same conditions.
As shown in Table 1, heterocyclic aromatic amines such as
aminopyridine and aminopyrimidine react readily with
substituted nitropyridines in the presence of selenium or
selenium dioxide and carbon monoxide under mild
conditions. The fact that 4-amino-3,5-dichloropyridine
gave none of the expected product suggests that the reaction
is sterically sensitive to ortho substituents of the aromatic
amine used (Table 1, entry 7). The yields of entries 2–5
were good and higher than those of entries 1 and 6. This
shows that the reactions are electronically influenced by
substituents on the aromatic rings (Table 01, entries 1–6). By
using this method, the symmetric N,N -bis(6-methoxy-3-
pyridyl)urea 8 (entry 8) can also be synthesized.
2.3. A possible reaction pathway of carbonylation
Although a detailed study of the reaction pathway has not
been performed, the present reactions can be mechanistic-
ally explained by the reaction pathway shown in Scheme 1.
Initial deoxygenation of the substituted nitropyridine
derivative with carbonyl selenide (SeCO), generated in
situ by the reaction of elemental selenium or selenium
dioxide with carbon monoxide in the presence of
Scheme 1. A possible reaction pathway for carbonylation.

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J. Chen et al. / Tetrahedron 59 (2003) 8251–8256
Scheme 2. Selenium or selenium dioxide-catalyzed carbonylation of substituted nitropyridines.
triethylamine,24,25 results in an intermediate(s) nitrene 2a
and/or nitrenoid 3a which further react with carbon
monoxide to form pyridyl isocyanate complex 4a. Finally,
4a reacts with aminopyridine derivatives to afford the
desired N,N0-dipyridylurea derivative 1a.
and an Applied Biosystem Mariner System 5303 in APCI
mode. 1H and 13C NMR spectra were obtained on a Bruker
DRX 400 spectrometer. Chemical shifts are reported in ppm
relative to tetramethylsilane (d-units) with dimethylsulf-
oxide-d6 as solvent.
It is known that selenium dioxide reacts with carbon
monoxide in the presence of triethylamine under very mild
conditions (108C, 0.1 MPa), to form carbonyl selenide
(COSe) in the same way as dose selenium.16,24 In our case,
when selenium dioxide goes through the first catalytic cycle,
the catalyst is transformed into elemental selenium due to
the reduction of selenium dioxide by carbon monoxide in
the catalytic system (Scheme 2). During the reaction the
substituted nitropyridine also acts as an oxidant, thus
playing an important role in promoting a catalytic cycle.
Products 1a as well as the catalysts can then be easily
obtained by simple phase separation.
4.2. Typical procedure for the synthesis of N-(2-pyridyl)-
N0-(6-methoxy-3-pyridyl)urea 1
Selenium (39.5 mg, 0.5 mmol), 2-aminopyridine (0.94 g,
10 mmol), 2-methoxy-5-nitropyridine (1.54 g, 10 mmol),
triethylamine (1.01 g, 10 mmol) and toluene (10 mL) were
successively introduced into a 100 mL stainless-steel
autoclave. The stirring rate was kept constant for all the
experiments. The reactor was sealed, flushed with 1.0 MPa
of carbon monoxide three times, pressurized with 3.0 MPa
carbon monoxide, and then placed in an oil bath preheated
to the 1308C. After the reaction was finished, the apparatus
was cooled to ambient temperature, and the remaining
carbon monoxide was evacuated. The reaction mixture was
filtered, and N-(2-pyridyl)-N0- (6-methoxy-3-pyridyl)urea
was collected and further purified by flash chromatography
(silica gel, v/v: hexane–AcOEt¼5:3) in 74% yield (1.82 g).
3. Conclusion
The mild reaction conditions, good yield and high
chemoselectivity of products, the one-step synthesis and
the replacement of noxious phosgene by carbon monoxide
combine to make the present procedure very useful for the
preparation of unsymmetric N,N0-dipyridylurea derivatives.
In summary, we have developed a catalytic synthetic
method to prepare unsymmetric N,N0-dipyridylurea deriva-
tives by combining reductive carbonylation of a nitropyri-
dine with the oxidative carbonylation of an aminopyridine
derivative in a one-pot reaction.
4.2.1. N-(2-Pyridyl)-N0-(6-methoxy-3-pyridyl)urea 1.
Colorless needle; mp 178–1808C; IR n/cm21 (KBr) 3221
(nN–H), 3012 (nC–H), 1693 (nCvO), 1596, 1558, 1495, 1481,
1
1431 (nCvC,CvN), 1383 (n–CH3), 782 (nC–H); H, NMR
(400 MHz, DMSO-d6, 238C) d 3.91 (s, 3H, OCH3), 6.73 (d,
J¼8.8 Hz, 1H, 50-H), 6.91 (t, J¼6.4 Hz, 1H, 5-H), 7.15 (d,
J¼8.0 Hz, 1H, 3-H), 7.620(td, J¼7.8, 1.2 Hz, 1H, 4-H), 7.91
(dd, J¼8.7, 2.8 Hz, 1H, 4 -H), 8.22 (d, J¼4.4 Hz, 1H, 6-H),
8.29 (s, 1H, 20-H), 9.48 (s, 1H, 70-H), 11.32 (s, 1H, 7-H);
13C, NMR (400 MHz, DMSO-d6, 238C) d 53.2 (OCH3),
110.0 (C-50), 112.2 (C-3), 116.8 (C-5), 129.2 (C-30), 132.0
(C-40), 138.1 (C-20), 138.3 (C-4), 145.6 (C-6), 152.9 (C-2),
153.5 (CvO), 160.0 (C-60); MS (ESI): m/z: 245 (15 MHþ),
151 (14), 125 (30), 121 (7), 95 (100%); HRMS (APCI):
MHþ, found 245.1021, C12H13N4O2 requires 245.1033.
4. Experimental
4.1. General remarks
Organic solvents were all reagent grade and used without
further purification. Aminopyridine derivatives, 2-methoxy-
5-nitropyridine, elemental selenium (99.999%), selenium
dioxide (98.0%), carbon monoxide (99.9%), triethylamine,
triphenylphosphine and other organic base were all used as
purchased. Purity of the products was determined by HPLC,
with MeOH–H2O as eluent. Melting points were deter-
mined on a Taike X-4 apparatus (Beijing, P. R. China) and
are uncorrected. Infrared spectra were recorded on a
Thermo Nicolet 470 instrument. Mass Spectra were
performed on a Finnigan LCQDUO ion trap Mass Spectro-
meter (Finnigan MAT, San Jose, CA, USA) in ESI mode
4.2.2. N-(3-Methyl-2-pyridyl)-N0-(6-methoxy-3-pyridyl)-
urea 2. Colorless needle; mp 173–1758C; IR n/cm21 (KBr)
3294 (nN–H), 2955 (nC–H), 1683 (nCvO), 1592, 1559, 1495
1
(nCvC,CvN), 1461, 1379 (n–CH3), 746 (nC–H); H, NMR
(400 MHz, DMSO-d6, 238C) d 2.05 (s, 3H, CH3), 3.85 (s,

J. Chen et al. / Tetrahedron 59 (2003) 8251–8256
8255
3H, OCH3), 6.84 (d, J¼8.7 Hz, 1H, 50-H), 7.02 (t, J¼6.5 Hz,
1H, 50-H), 7.64 (d, J¼4.1 Hz, 1H, 4-H), 7.97 (d, J¼8.8 Hz,
1H, 4 -H), 8.22 (s, 1H, 20-H), 8.36 (d, J¼8.4 Hz, 1H, 6-H),
8.66 (s, 1H, 70-H), 11.81 (s, 1H, 7-H); 13C, NMR (400 MHz,
DMSO-d6, 238C) d 17.0 (CH3), 53.2 (OCH3), 110.1 (C-50),
117.8 (C-5), 121.4 (C-3), 129.7 (C-30), 132.2 (C-40), 138.1
(C-20), 139.7 (C-4), 143.5 (C-6), 151.2 (C-2), 152.8 (CvO),
159.6 (C-60); MS (ESI): m/z: 259 (2 MHþ), 151 (12), 135
(35), 125 (72), 110 (9), 109 (100%); HRMS (APCI): MHþ,
found 259.1172, C13H15N4O2 requires 259.1189.
(nN–H), 3049 (nC–H), 1712 (nCvO), 1622, 1598, 1557, 1484
(nCvC,CvN), 1381 (n–CH3), 829 (nC–H); 1H, NMR
(400 MHz, DMSO-d6, 238C) d 3.84 (s, 3H, OCH3), 6.82
(d, J¼8.7 Hz, 1H, 50-H), 7.68 (d, J¼8.0 Hz, 1H, 3-H), 7.85
(d, J¼8.1 Hz, 1H, 4-H), 7.870 (d, J¼8.7 Hz, 1H, 40-H), 8.26
(s, 1H, 20-H), 9.54 (s, 1H, 7 -H), 10.32 (s, 1H, 7-H); 13C,
NMR (400 MHz, DMSO-d6, 238C) d 53.2 (OCH3), 110.2
(C-50), 113.1 (C-3), 123.5 (C-5), 129.7 (C-30), 131.6 (C-40),
137.5 (C-20), 138.2 0(C-4), 145.5 (C-6), 151.4 (C-2), 152.2
(CvO), 159.5 (C-6 ); MS (ESI): m/z: 279 (13 MHþ) 151
(40), 129 (100), 125 (2%); HRMS (APCI): MHþ, found
279.0656, C12H12N4O2Cl requires 279.0643.
4.2.3. N-(4-Methyl-2-pyridyl)-N0-(6-methoxy-3-pyridyl)-
urea 3. Colorless powder; mp 188–1898C; IR n/cm21
(KBr) 3219 (nN–H), 3019 (nC–H), 1695 (nCvO), 1619, 1596,
1562, 1522, 1490 (nCvC,CvN), 1459, 1382 (n–CH3), 815
4.2.7. N,N0-Bis(6-methoxy-3-pyridyl)urea 8. Colorless
needle; mp 228–2318C; IR n/cm21 (KBr) 3283 (nN–H),
3009 (nC–H), 1638 (nCvO), 1605, 1580, 1565, 1494, 1441
(nCvC,CvN), 1382 (n–CH3), 821 (nC–H); 1H, NMR
(400 MHz, DMSO-d6, 238C) d 3.82 (s, 3H, OCH3), 6.79
(d, J¼0 8.8 Hz, 1H, 5-H/50-H), 7.83 (dd, J¼8.8, 2.5 Hz, 1H,
4-H/4 -H), 8.21 (s, 1H, 2-H/20-H), 8.65 (s, 1H, 7-H/70-H);
13C, NMR (400 MHz, DMSO-d6, 238C) d 53.1 (OCH3),
110.0 (C-5/C-50), 130.5 (C-3/C-30), 131.30(C-4/C-40), 137.1
(C-2/C-20), 153.3 (CvO), 159.1 (C-6/C-6 ); MS (ESI): m/z:
275 (7 MHþ) 151 (100), 125 (27), 110 (2%); HRMS
(APCI): MHþ, found 275.1139, C13H15N4O3 requires
275.1139.
1
(nC–H); H, NMR (400 MHz, DMSO-d6, 238C) d 2.29 (s,
3H, CH3), 3.84 (s, 3H, OCH3), 6.82 (d, J¼8.9 Hz, 1H, 50-H),
6.86 (d, J¼5.2 Hz, 1H, 5-H), 7.25 (s, 1H, 3-H), 7.91 (dd,
J¼8.8, 2.08 Hz, 1H, 40-H), 8.14 (d, J¼5.2 Hz, 1H, 6-H), 8.29
(s, 1H, 2 -H), 9.46 (s, 1H, 70-H), 10.66 (s, 1H, 7-H); 13C,
NMR (400 MHz, DMSO-d6, 238C) d 20.9 (CH3), 53.1
(OCH3), 110.2 (C-50), 111.9 (C-3), 118.7 (C-5), 129.8
(C-30), 131.7 (C-40), 137.6 (C-20), 1460.5 (C-6), 149.3 (C-4),
152.5 (CvO), 152.8 (C-2), 159.4 (C-6 ); MS (ESI): m/z: 259
(18 MHþ), 151 (7), 135 (23), 125 (40), 110 (3), 109 (100%);
HRMS (APCI): MHþ, found 259.1189, C13H15N4O2
requires 259.1189.
4.2.8. N-(2-Pyrimidyl)-N0-(6-methoxy-3-pyridyl)urea 9.
Colorless powder; mp 220–2218C; IR n/cm21 (KBr) 3063
(nN–H), 2975 (nC–H), 1697 (nCvO), 1622, 1583, 1556, 1518,
1491, 1438 (nCvC,CvN), 1455, 1384 (n–CH3), 799 (nC–H);
1H, NMR (400 MHz, DMSO-d6, 238C) d 3.85 (s, 3H,
OCH3), 6.83 (d, J¼8.7 Hz, 1H, 50-H), 7.15 (t, J¼4.8 Hz, 1H,
5-H), 7.95 (dd, J¼8.8, 2.7 Hz, 1H, 40-H), 8.36 (s,0 1H, 20-H),
8.68 (d, J¼5.2 Hz, 2H, 4-H/6-H), 10.20 (s, 1H, 7 -H), 11.29
(s, 1H, 7-H); 13C, NMR (400 MHz, DMSO-d6, 238C) d 53.2
(OCH3), 110.1 (C-50), 115.1 (C-5), 129.2 (C-30), 132.3
(C-40), 138.3 (C-20), 151.8 (CvO), 157.8 (C-2), 158.2 (C-4/
C-6), 159.8 (C-60); MS (ESI): m/z: 246 (22 MHþ) 151 (64),
96 (100%); HRMS (APCI): MHþ, found 246.1001,
C11H12N5O2 requires 246.0986.
4.2.4. N-(5-Methyl-2-pyridyl)-N0-(6-methoxy-3-pyridyl)-
urea 4. Colorless powder; mp 1788C; IR n/cm21 (KBr)
3209 (nN–H), 3092 (nC–H), 1675 (nCvO), 1611, 1579, 1545,
1
1492 (nCvC,CvN), 1386 (n–CH3), 835 (nC–H), H, NMR
(400 MHz, DMSO-d6, 238C) d 2.23 (s, 3H, CH3), 3.84 (s,
3H, OCH3); 6.82 (d, J¼8.8 Hz, 1H, 50-H), 7.38 (d, J¼
8.0 Hz, 1H, 3-H); 7.58 (d, J¼7.9 Hz, 1H, 4-H), 7.91 (d, J¼
8.7 Hz, 1H, 40-H), 8.11 (s, 1H, 6-H), 8.28 (s, 1H, 20-H), 9.42
(s, 1H, 70-H), 10.46 (s, 1H, 7-H); 13C, NMR (400 MHz,
DMSO-d6, 238C) d 17.2 (CH3), 53.1 (OCH3), 110.1 (C-50),
111.5 (C-3), 126.3 (C-5), 130.0 (C-30), 131.7 (C-40), 137.5
(C-20), 139.2 (C-4), 146.3 (C-6), 150.7 (C-2), 152.6 (CvO),
159.4 (C-60); MS (ESI): m/z: 259 (14 MHþ) 151 (6), 135
(17), 125 (36), 110 (3), 109 (100%); HRMS (APCI): MHþ,
found 259.1167, C13H15N4O2 requires 259.1189.
4.2.9. N-(4,6-Dimethyl-2-pyrimidyl)-N0-(6-methoxy-3-
pyridyl)urea 10. Colorless powder; mp 198–2018C; IR n/
cm21 (KBr) 3281 (nN–H), 2949 (nC–H), 1700 (nCvO), 1638,
1602, 1565, 1492 (nCvC,CvN), 1380 (n–CH3), 839 (nC–H);
1H, NMR (400 MHz, DMSO-d6, 238C) d 2.51 (s, 6H, CH3),
3.83 (s, 3H, OCH3), 6.79 (d, J¼8.8 Hz, 1H, 50-H), 6.90
(s, 1H, 5-H), 7.80 (d, J¼8.7 Hz, 1H, 40-H), 8.19 (s, 1H, 20-
H), 8.64 (s, 1H, 70-H), 11.75 (s, 1H, 7-H); 13C, NMR
(400 MHz, DMSO-d6, 238C) d 23.4 (CH3), 53.1 (OCH3),
110.2 (C-50), 113.8 (C-5), 129.6 (C-30), 131.5 (C-40), 137.2
(C-20), 153.3 (CvO), 157.4 (C-2), 159.6 (C-60), 167.6 (C-4/
C-6); MS (ESI): m/z: 274 (18 MHþ), 150 (3), 125 (4) 124
(100%); HRMS (APCI): MHþ, found 274.1300,
C13H16N5O2 requires 274.1298.
4.2.5. N-(6-Methyl-2-pyridyl)-N0-(6-methoxy-3-pyridyl)-
urea 5. Colorless needle; mp 210–2128C; IR n/cm21 (KBr)
3225 (nN–H), 2997 (nC–H), 1699 (nCvO), 1626, 1598, 1565,
1
1496 (nCvC,CvN), 1460, 1383 (n–CH3), 750 (nC–H); H,
NMR (400 MHz, DMSO-d6, 238C) d 2.46 (s, 3H, CH3), 3.83
(s, 3H, OCH3), 6.82 (d, J¼8.8 Hz, 1H, 50-H), 6.87 (d, J¼
7.3 Hz, 1H, 3-H), 7.18 (d, J¼8.0 Hz, 1H, 5-H), 7.603 (t,
J¼8.0 Hz, 1H0, 4-H), 7.91 (dd, J¼8.7, 2.6 Hz, 1H, 4 -H),
8.28 (s, 1H, 2 -H), 9.54 (s, 1H, 70-H), 10.86 (s, 1H, 7-H);
13C, NMR (400 MHz, DMSO-d6, 238C) d 23.6 (CH3),
53.1 (OCH3), 108.7 (C-3), 110.2 (C-50), 116.5 (C-5), 129.9
(C-30), 131.5 (C-40), 137.2 (C-20), 1380.9 (C-4), 152.3 (C-2),
152.5 (CvO), 155.3 (C-6), 159.4 (C-6 ); MS (ESI): m/z: 259
(8 MHþ) 151 (7), 135 (63), 125 (84), 110 (6), 109 (100%);
HRMS (APCI): MHþ, found 259.1172, C13H15N4O2
requires 259.1189.
4.2.10. N-(4,6-Dimethoxy-2-pyrimidyl)-N0-(6-methoxy-
3-pyridyl)urea 11. Colorless flakes; mp 228–2298C; IR
n/cm21 (KBr) 3271 (nN–H), 3112 (nC–H), 1700 (nCvO),
1606, 1564, 1577, 1552 (nCvC,CvN), 1459, 1378 (n–CH3),
4.2.6. N-(5-Chloro-2-pyridyl)-N0-(6-methoxy-3-pyridyl)-
urea 6. Colorless needle; mp 2118C; IR n/cm21 (KBr) 3211
812 (nC–H); H, NMR (400 MHz, DMSO-d6, 238C) d 3.83
0
(s, 3H, C6 –OCH3), 3.94 (s, 6H, C4–OCH3/C6–OCH3),
1

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J. Chen et al. / Tetrahedron 59 (2003) 8251–8256
5.90 (s, 1H, 5-H), 6.83 (d, J¼8.4 Hz, 1H, 50-H), 7.92 (d, J¼
8.3 Hz, 1H, 40-H), 8.27 (s, 1H, 20-H), 10.04 (s, 1H, 70-H),
11.00 (s, 1H, 7-H); 13C, NMR (400 MHz, DMSO-d6, 238C)
5. Singha, N. C.; Sathyanarayana, D. N. J. Chem. Soc. Perkin
Trans. 2 1997, 157–162.
6. Corbin, P. S.; Zimmerman, S. C.; Thiessen, P. A.; Hawryluk,
N. A.; Murray, T. J. J. Am. Chem. Soc. 2001, 123,
10475–10488.
0
d 53.2 (C6 –OCH3), 54.4 (C4–OCH3/C6–OCH3), 82.8
(C-5), 110.1 (C-50), 129.3 (C-30), 131.2 (C-40), 137.9 (C-20),
151.7 (CvO), 156.9 (C-2), 159.8 (C-60), 171.3 (C-4/C-6);
MS (ESI): m/z: 306 (14 MHþ), 182 (8), 156 (100), 125
(6%); HRMS (APCI): MHþ, found 306.1179, C13H16N5O4
requires 306.1197.
7. Cicha, W. V. Chem. Engng News 1998, 76, 2.
8. Ryan, T. A. Chem. Engng News 1998, 76, 2.
9. Cenini, S.; Ragaini, F. J. Mol. Catal. A: Chem. 1996, 109,
1–25.
10. Cenini, S.; Ragaini, F. Catalytic Reductive Carbonylation of
Organic Nitro Compounds; Kluwer Academic: Dordrecht,
1997.
4.2.11. N-(2,6-Dimethyl-4-pyrimidyl)-N0-(6-methoxy-3-
pyridyl)urea 12. Colorless powder; mp 163–1668C; IR n/
cm21 (KBr) 3284 (nN–H), 2947 (nC–H), 1703 (nCvO), 1601,
11. Tafesh, A. M.; Weiguny, J. Chem. Rev. 1996, 96, 2035–2052.
12. Paul, F. Coord. Chem. Rev. 2000, 203, 269–323.
13. Franz, R. A.; Applegath, F.; Morris, F. V.; Baiocchi, F. J. Org.
Chem. 1961, 26, 3306–3308.
1
1559, 1493 (nCvC,CvN), 1381 (n–CH3), 746 (nC–H); H,
NMR (400 MHz, DMSO-d6, 238C) d 2.34 (s, 3H, C6–CH3),
2.50 (s, 3H, C2–CH3), 3.83 (s, 3H, OCH3), 6.78 (s, 1H,
5-H), 6.84 (d, J¼8.8 Hz, 1H, 50-H), 7.950(d, J¼8.7 Hz, 1H,
40-H), 8.27 (s, 1H, 20-H), 10.21 (s, 1H, 7 -H), 11.73 (s, 1H,
7-H); 13C, NMR (400 MHz, DMSO-d6, 238C) d 24.8
(C6–CH3), 26.3 (C2–CH3), 54.1 (OCH3), 104.7 (C-5),
111.0 (C-50), 130.3 (C-30), 132.5 (C-40), 138.0 (C-20), 152.9
(CvO), 158.4 (C-4), 159.3 (C-60), 166.8 (C-6), 168.0 (C-2);
MS (ESI): m/z: 274 (10 MHþ), 151 (4), 150 (12), 125 (15),
124 (100%); HRMS (APCI): MHþ, found 274.1305,
C13H16N5O2 requires 274.1298.
14. Franz, R. A.; Applegath, F.; Morris, F. V.; Baiocchi, F.; Bolze,
C. J. Org. Chem. 1961, 26, 3309–3312.
15. Sonoda, N. J. Am. Chem. Soc. 1971, 93, 6344–6344.
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18. Kim, H. S.; Kim, Y. J.; Lee, H.; Lee, S. D.; Chin, C. S. J. Catal.
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Patent PL 149935, 1990.
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