Desulfitative cross-coupling of protecting group-free 2-thiouracil derivatives with organostannanes

Article abstract of DOI:10.1021/jo1003482

We here report a unique and efficient copper bromide mediated pallado-catalyzed coupling of protecting group-free 2-thiouracil derivatives with organostannanes. The nature of the copper appears to be crucial for successful cross coupling.

Full text of DOI:10.1021/jo1003482

pubs.acs.org/joc
coupling with boronic acids,4,5 organostannanes,6 or arylsil-
Desulfitative Cross-Coupling of Protecting Group-
Free 2-Thiouracil Derivatives with Organostannanes
oxanes7 and allows access to original, and previously unob-
tained, functionalizations.8 The scope of this novel base free
reaction has been extended considerably to enable the coupling
reaction between organosulfur and organometallic reagents to
overcome the failure encountered by the traditional C-C bond
formation method.9 In independent studies, our group has
shown that the carboxylate counterion is not essential for the
catalytic cycle to proceed with stannane derivatives, and can be
efficiently replaced by the readily accessible copper(I) bromide-
‡
Qi Sun,†,‡ Franck Suzenet,*,‡ and Gerald Guillaumet
ꢀ
†School of Pharmaceutical Science, Peking University, 38,
Xueyuan Road, Haidian District, Beijing, China, 100191, and
‡
ꢀ
Institut de Chimie Organique et Analytique, Universite
d’Orleꢀans, UMR-CNRS 6005, rue de Chartres, BP 6759,
ꢀ
45067 Orleans cedex 2, France
dimethyl sulfide complex (CuBr Me2S).10 This approach has
3
franck.suzenet@univ-orleans.fr
Received February 24, 2010
been recently successfully applied to various substrates.11
In the context of the synthesis of combinatorial libraries of
2-aryl-1,4-dihydropyrimidines as potential non-nucleosidic
inhibitors of hepatitis B virus replication, Kappe and co-
workers developed a direct C-C cross-coupling of cyclic
thioureas containing a latent free-thiol functionality under
microwave conditions in high yields.12 This promising de-
sulfitative coupling was successfully applied to thioamide
fragments13 and oxazolinethiones14 with boronic acids and
stannanes, and extended to arylsiloxanes for the former and
a variety of terminal alkynes for the latter.15
2-Thiouracil (1) and related modified pyrimidine nucleo-
bases are important reagents for the synthesis of different
kinds of heterocycles with potential biological activity. Their
special structures have also emerged as a building block in
natural or synthetic molecules. Furthermore, uracil has been
proposed as the central scaffold in the butterfly strategies for
the synthesis of original non-nucleoside reverse transcriptase
inhibitors (NNRTIs).16 Therefore the acyl thiourea moiety
(-NH-C(S)-NH-C(O)-), which can also be found in
many easily accessible modified pyrimidines, appeared to
be an interesting function in order to access various sub-
stituted pyrimidin-4-ones. In this paper, we report a unique
and efficient copper bromide mediated pallado-catalyzed
coupling of protecting group-free 2-thiouracil derivatives
with organostannanes.
We here report a unique and efficient copper bromide
mediated pallado-catalyzed coupling of protecting group-
free 2-thiouracil derivatives with organostannanes. The
nature of the copper appears to be crucial for successful
cross coupling.
Heterocycle structures have played an important role in
lead discovery and biological activities in the pharmaceutical
industry and academic research.1 Metal-catalyzed coupling
protocols have developed into powerful tools for synthetic
chemists and have proved highly successful in the construc-
tion and functionalization of heteroaromatic series over the
past two decades.2 However, the ability to selectively form
site specific covalent bonds within a sensitive molecule under
mild conditions and without the need for protection-
deprotection remains an attractive challenge for organic
chemists.
Most transition metal cross-coupling procedures involve
the interaction of an electrophilic organohalide (or related
substrate) with a nucleophilic organometallic reagent. The
limited stability and/or accessibility of the corresponding
heteroaromatic derivatives appears somewhat problematic
and led Liebeskind and Srogl to develop a new efficient
palladium-catalyzed cross-coupling reaction involving thiol
ester3 and thioether4 type species. This method requires a
stoichiometric amount of a copper(I) carboxylate for efficient
Encouraged by the success of Kappe’s work,12,13 we ex-
plored the Liebeskind-Srogl cross-coupling between the CdS
of 2-thiouracil 1 with phenylboronic acid 2. Unfortunately,
(6) Egi, M.; Liebeskind, L. S. Org. Lett. 2003, 5, 801.
(7) Mehta, V. P.; Sharma, A.; Van der Eycken, E. Adv. Synth. Catal. 2008,
350, 2174.
(8) (a) Leconte, N.; Keromnes-Wuillaume, A.; Suzenet, F.; Guillaumet,
€
G. Synlett 2007, 204. (b) Leconte, N.; Pellegatti, L.; Tatibouet, A.; Suzenet,
F.; Rollin, P.; Guillaumet, G. Synthesis 2007, 857. (c) Alphonse, F.-A.;
Suzenet, F.; Keromnes, A.; Lebret, B.; Guillaumet, G. Synthesis 2004, 2893.
ꢀ
(9) Prokopcova, H.; Kappe, C. O. Angew. Chem., Int. Ed. 2008, 47, 3674.
(10) Alphonse, F.-A.; Suzenet, F.; Keromnes, A.; Lebret, B.; Guillaumet,
G. Org. Lett. 2003, 5, 803.
(11) (a) Richardson, C.; Rewcastle, G. W.; Hoyer, D.; Denny, W. A.
€
J. Org. Chem. 2005, 70, 7436. (b) Schleiss, J.; Rollin, P.; Tatibouet, A. Angew.
Chem., Int. Ed. 2010, 49, 577.
(12) Lengar, A.; Kappe, C. O. Org. Lett. 2004, 6, 771.
(13) (a) Arshad, N.; Hashim, J.; Kappe, C. O. J. Org. Chem. 2009, 74,
(1) (a) Horton, D. A.; Bourne, G. T.; Smythe, M. L. Chem. Rev. 2003, 103,
893. (b) Font, D.; Heras, M.; Villalgordo, J. M. J. Comb. Chem. 2003, 5, 311.
(2) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457.
(3) (a) Savarin, C.; Srogl, J.; Liebeskind, L. S. Org. Lett. 2000, 2, 3229. (b)
Liebeskind, L. S.; Srogl, J. J. Am. Chem. Soc. 2000, 122, 11260.
(4) Liebeskind, L. S.; Srogl, J. Org. Lett. 2002, 4, 979.
ꢀ
5118. (b) Prokopcova, H.; Kappe, C. O. J. Org. Chem. 2007, 72, 4440.
(14) Silva, S.; Tardy, S.; Routier, S.; Suzenet, F.; Tatibouet, A.; Rauter,
A. P.; Rollin, P. Tetrahedron Lett. 2008, 49, 5583.
(15) Silva, S.; Sylla, B.; Suzenet, F.; Tatibouet, A.; Rauter, A. P.; Rollin,
P. Org. Lett. 2008, 10, 853.
(5) (a) Savarin, C.; Srogl, J.; Liebeskind, L. S. Org. Lett. 2001, 3, 91. (b)
Alphonse, F.-A.; Suzenet, F.; Keromnes, A.; Lebret, B.; Guillaumet, G.
Synlet. 2002, 447.
(16) (a) Dasa, K.; Lewib, P. J.; Hughesc, S. H.; Arnold, E. Prog. Biophys.
Mol. Biol. 2005, 88, 209. (b) Yu, M.; Liu, X.; Li, Z.; Liu, S.; Pannecouque, C.;
De Clercq, E. Bioorg. Med. Chem. 2009, 17, 7749.
DOI: 10.1021/jo1003482
r
Published on Web 04/01/2010
J. Org. Chem. 2010, 75, 3473–3476 3473
2010 American Chemical Society

Sun et al.
JOCNote
SCHEME 1. Liebeskind-Srogl Reaction on Thiouracil 1 and
SMe-Thiouracil 4
TABLE 1. Optimization of Reaction Conditions
PhSnBu3
(equiv)
Pd(PPh3)4
(equiv)
CuBr Me2S
3
time yield a
entry
(equiv)
(h)
(%)
1
2
3
4
5
6
7
2.2
2.2
2.2
2.2
2.2
2.2
1.2
0.1
0.05
0.03
2.2
2.2
2.2
2.2
14
14
14
14
14
14
14
68
62
41
0
0
40
47
SCHEME 2. Liebeskind-Srogl Reaction on N-Protected
Thiouracil 5
0.05
0.05
0.05
1.2
2.2
aIsolated yield after column chromatography.
TABLE 2. Copper(I)-Promoted Palladium-Catalyzed Cross-Coupling
of 2-Thiouracil 1 with Organostannanes
attempts to isolate the desired coupled compound 3a under
microwave irradiation or conventional reflux conditions with
3 equiv of copper(I) thiophene-2-carboxylate (CuTC) failed
(Scheme 1).
We first surmised that in this particular case, a thioether
function was essential for the success of the reaction and
therefore synthesized the methylthioether 4 by reaction of 1
with sodium hydroxide and methyl iodide.17 Compound
4 was then refluxed with 2 in the presence of Pd(PPh3)4
(5 mol %) and CuTC (3 equiv). However, yet again, the
reaction did not proceed (Scheme 1).
entry
organostannane R
time (h)
product
yielda (%)
1
2
3
4
5
6
3-nitrophenyl (7b)
4-methoxyphenyl (7c)
2-furyl (7d)
2-thienyl (7e)
3-pyridinyl (7f)
PhCHdCH- (7g)
24
24
14
14
24
48
3b
3c
3d
3e
3f
63
52
64
62
53
36
This result led us to consider more closely the modular
synthesis of functionalized pyrimidinones via sulfide cross-
coupling chemistry recently reported in the literature.18 For
all the examples reported, the reaction was carried out
starting from an N-3 protected (alkylated) pyrimidone. To
assess the crucial impact of this protection, we introduced an
allyl group on N-3 according to Mizutani’s protocol,19 to
provide the desired N-substituted product 5 in 65% yield.
Refluxing a solution of 5 with phenylboronic acid 2, Pd-
(PPh3)4 (5 mol %), and 3 equiv of CuTC in THF provided the
desired coupling product 6 in 85% yield (Scheme 2).
At this stage, experimental results indicated that classic
Liebeskind-Srogl reaction conditions were not suitable for
cross-coupling with a protecting group-free acyl thiourea
moiety (-NH-C(S)-NH-C(O)-) present in 2-thiouracil
derivatives for example. Considering a probable interaction
between the carboxylate moiety of the CuTC cofactor and
the free NH of the thiouracil scaffold, we were intrigued by the
interest of using the initial copper source, i.e. CuBr, that wehad
found for the Pd-catalyzed cross-coupling reactions of hetero-
aromatic thioethers with organostannanes.10 Initially, we
examined the cross-coupling reaction of 2-thiouracil 1 with
the commercially available phenyltri-n-butyltin 7a catalyzed
by Pd(PPh3)4 (10 mol %) in the presence of 2.2 equiv of
3g
aIsolated yield after column chromatography.
and in particular the C-C bond formation was confirmed by
careful analysis of the 1H/13C NMR spectra and MS data.
A series of experiments were then performed to optimize
the experimental conditions. Loading down the palladium
catalyst to 5 mol % gave a similar yield (Table 1, entry 2)
while 3 mol % afforded poorer results (Table 1, entry 3). The
palladium catalyst as well as the copper(I) cofactor appear to
be essential for the reaction to proceed (Table 1, entries 4
and 5). Decreasing the amount of CuBr Me2S or PhSnBu3 to
3
1.2 equiv also had a detrimental effect on productivity
(Table 1, entries 6 and 7). Finally, longer reaction times did
not improve the yields, and shorter reaction times or micro-
wave activation for 0.5 h at 100 °C were not conclusive.
We then explored the possibility of generalizing this cross-
coupling reaction to various organostannanes using the
previously optimized experimental conditions. The results
are depicted in Table 2. 2-Thiouracil 1 was reacted with
electron-poor (7b) or electron-rich aryltributylstannanes (7c)
to provide the corresponding products in good yields (entries
1 and 2). Different heteroarylstannanes as well as π-deficient
3-stannylpyridine proved to be consistent with this cross-
coupling and afforded the desired products 3d, 3e, and 3f, in
64%, 62%, and 53% yields, respectively (entries 3, 4, and 5).
Vinyltributyltin derivative 7g was also cross-coupled with 1
in moderate yields (entry 6).
CuBr Me2S. After 14 h of reflux in THF, we were delighted to
3
isolate product 3a in 66% yield (Table 1, entry 1). The structure
(17) See the Supporting Information.
(18) (a) Kusturin, C.;Liebeskind, L. S.;Rahman, H.;Sample, K.;Schweitzer,
B.; Srogl, J.; Neumann, W. L. Org. Lett. 2003, 5, 4349. (b) Rousseau, J.;
Krisciuniene, V.; Rimkeviciute, I.; Rousseau, C.; Amankaviciene, V.; Sackus,
The extension of these direct Pd-catalyzed, Cu(I)-mediated
reactions to modified bases appears particularly interesting
especially for medicinal chemists, and was therefore investigated.
€
A.; Tatibouet, A.; Rollin, P. Monatsh. Chem. 2009, 140, 339.
(19) Mizutani, M.; Sanemitsu, Y.; Tamaru, Y.; Yoshida, Z. J. Org. Chem.
1985, 50, 764.
3474 J. Org. Chem. Vol. 75, No. 10, 2010

Sun et al.
JOCNote
TABLE 3. Copper(I)-Promoted Palladium-Catalyzed Cross-Coupling
of 2-Thiouracil Derivatives with Phenylstannane 7a
stannanes 7e and 7f (Table 4, entries 6 and 7). This led us to
assess the selective sulfide over halide cross-coupling chemis-
try18a on the protecting group-free pyrimidinone 12. Phenyl
and hetaryl stannanes 7a and 7e were therefore reacted with
the 2-methylsulfanyl-3-bromopyridin-2-one 12 and bromo deri-
vatives 12a and 12e were isolated with very high chemoselectivity
(Table 4, entries 8 and 9).
In summary, the hitherto unprecedented efficient reaction
of 2-thiouracil derivatives with organostannanes has been
reported in moderate to good yields. This approach avoids
the need for protection-deprotection of the acyl thiourea
moiety (-NH-C(S)-NH-C(O)-) present in numerous
scaffolds of biological interest. Interestingly, the nature of
the copper(I) source appears to be crucial for successful
coupling and also provides complementary coupling condi-
tions versus those previously published.
entry
R1
Me (8)
H (9)
CO2C2H5 (10)
Me (11)
X-R2
product
yielda (%)
1
2
3
4
C-H
C-CH3
C-H
N
8a
9a
10a
11a
58
65
59
67
aIsolated yield after column chromatography.
TABLE 4. Copper Sources and Chemoselectivity of the Palladium-
Catalyzed Cross-Coupling of Thiouracil Derivatives
Experimental Section
Typical Procedure for the Palladium-Catalyzed Modified
Liebeskind-Srogl Cross-Coupling Reaction. 2-Thiouracil 1
(0.4 mmol), tributyltin derivative (0.88 mmol), and CuBr Me2S
3
(0.88 mmol) were added into dry THF (5 mL) under Ar. The
solution was stirred at rt for 10 min and Pd(PPh3)4 (0.02 mmol)
was added. The resulting mixture was refluxed for 24 h. The
reaction mixture was then filtrated on Celite and washed with
EtOAc (10 mL). After evaporation, the product was purified by
column chromatography to give the desired product.
yieldb
product (%)
entry
R1, R2
R-SnBu3
copper
1
2
3
4
5
6
7
8
9
H, H (1)
H, H (1)
7a
7a
7a
7a
7a
7e
7f
CuTC (2.2 equiv)
CuMeSal (2.2 equiv)
CuTC (2.2 equiv)
CuMeSal (2.2 equiv)
3a
3a
3a
3a
0
0
0
2-Phenyl-3H-pyrimidin-4-one (3a).22 Eluent: PE:EA (1:1),
then (1:2). Yield: 68%; white needle solid, mp 204-206 °C.
1H NMR (250 MHz, CDCl3): δ 13.12 (1H, s), 8.18-8.22 (2H,
m), 8.12 (1H, d, J=6.5 Hz), 7.54-7.57 (3H, m), 6.44 (1H, d, J=
6.5 Hz). 13C NMR (62.5 MHz, CDCl3): δ 165.3, 158.1, 156.1,
132.6, 132.4, 129.5, 128.1, 114.1. IR (cm-1): 3070, 2956, 1644,
1602, 1532, 1500. MS: 173.0 [M þ 1]þ.
Me, H (4)a
Me, H (4)
Me, H (4)
Me, H (4)
Me, H (4)
Me, Br (12)a
Me, Br (12)
0
CuBr Me2S (2.2 equiv) 3a
3
63
84
57
70
58
CuBr Me2S (2.2 equiv) 3e
3
CuBr Me2S (2.2 equiv) 3f
3
7a
7e
CuBr Me2S (2.2 equiv) 12a
3
2-(3-Nitrophenyl)-3H-pyrimidin-4-one (3b).23 Eluent: EA.
CuBr Me2S (2.2 equiv) 12e
3
aSee ref 21 for the synthesis of compounds 4 and 12. bIsolated yield
after column chromatography.
1
Yield: 63%, light yellow solid, mp 265 °C dec. H NMR (250
MHz, DMSO-MeOD): δ 9.04 (1H, s), 8.54 (1H, d, J=8.25 Hz),
8.47 (1H, dd, J=1 Hz, 8.25 Hz), 8.24 (1H, d, J=6.5 Hz), 7.85
(1H, d, J=8.25 Hz), 6.53 (1H, d, J=6.5 Hz). 13C NMR (62.5
MHz, DMSO-MeOD þ TFA): δ 165.4, {C(O)TFA: 159.6, 158.9,
158.3, 157.7}, 158.0, 155.6, 148.4, 135.7, 134.3, 130.7, 126.2,
122.9, 112.1. IR (cm-1): 3070, 1675, 1620, 1597, 1524, 1353,
1330. MS: 218.0 [M þ 1]þ.
The results are reported in Table 3. 2-Thiouracil derivatives 8, 9,
and 10 substituted with methyl in position 5 or 6 or with an ester
group in position 6 were reacted with phenytributylstannane 7a
to produce the corresponding products in good yields (Table 3,
entries 1-3). Finally, 6-aza-2-thiothymine 11 also proved to be
an excellent coupling substrate, since 11a was isolated in 67%
yield after column chromatography (Table 3, entry 4).
2-(4-Methoxyphenyl)-3H-pyrimidin-4-one (3c). Eluent: EA.
Yield: 52%, white solid, mp 208-209 °C. 1H NMR (250
MHz, CDCl3): δ 13.01 (1H, s), 8.18 (2H, d, J = 9 Hz), 8.09
(1H, d, J=6.5 Hz), 7.03 (2H, d, J=9 Hz), 6.39 (1H, d, J=6.75
Hz), 3.89 (3H, s). 13C NMR (62.5 MHz): δ 165.3, 163.3, 157.8,
156.2, 129.9, 124.7, 114.9, 113.1, 55.9. IR (cm-1): 2840, 1646,
1607, 1538, 1509, 1253. MS: 203.0 [M þ 1]þ. HRMS (ESI): m/z
calcd for C11H10N2O2Na [M þ Na]þ 225.0640, found 225.0648.
5-Methyl-2-phenyl-3H-pyrimidin-4-one (8a).23 Eluent: PE:EA
This specific reactivity of the RSnBu3/CuBr reactant
couple was highly unexpected.
To check whether it was the boronic acid or the CuTC that
was responsible for the absence of reactivity in the Liebeskind-
Srogl conditions, we engaged the cross coupling between
stannane 7a and 2-thiouracil 1 in the presence of Pd(PPh3)4
and 2.2 equiv of CuTC or CuMeSal20 in accordance with
Liebeskind conditions6 (Table 4, entries 1 and 2). The absence
of any coupled product 3a (Table 4, entry 1) shows that the
nature of the copper(I) source appears to be crucial for
successful coupling. This absence of reactivity in the presence
of copper carboxylate was confirmed starting from the NH-free
2-methysulfanylpyrimidin-2-one 4 (Table 4, entries 3 and 4),
while using CuBr, the desired product 3a was isolated in 63%
yields (Table 4, entry 5). This reactivity was confirmed with
1
(3:1), then (1:1). Yield: 58%, white solid, mp 190-192 °C. H
NMR (250 MHz, CDCl3): δ 12.91 (1H, s), 8.19-8.23 (2H, m),
8.01 (1H, s), 7.51-7.54 (3H, m), 2.14 (3H, s). 13C NMR (62.5
MHz, CDCl3): δ 165.7, 155.8, 153.1, 132.6, 132.1, 129.3, 127.8,
123.3, 13.3. IR (cm-1): 3064, 2920, 1639, 1605, 1547, 1508, 1475,
1313. MS: 187.5 [M þ 1]þ.
6-Methyl-2-phenyl-3H-pyrimidin-4-one (9a).22 Eluent: PE:EA
1
(3:1), then (1:1). Yield: 65%, white solid, mp 215-216 °C. H
(22) Zanatta, N.; Fantinel, L.; Lourega, R. V.; Bonacorso, H. G.;
Martins, M. A. P. Synthesis 2008, 358.
(20) CuMeSal=copper(I) 3-methylsalicylate.
(21) Barrett, H. W.; Goodman, I.; Dittmer, K. J. Am. Chem. Soc. 1948,
70, 1753.
(23) Medwid, J. B.; Paul, R.; Baker, J. S.; Brockman, J. A.; Du, M. T.;
Hallett, W. A.; Hanifin, J. W.; R., A. H., Jr.; Tarrant, M. E. J. Med. Chem.
1990, 33, 1230.
J. Org. Chem. Vol. 75, No. 10, 2010 3475

Sun et al.
JOCNote
NMR (250 MHz, CDCl3): δ 13.16 (1H, s), 8.17-8.21 (2H, m),
7.50-7.54 (3H, m), 6.30 (1H, d, J=0.75 Hz), 2.39 (3H, d, J=0.75
Hz). 13C NMR (62.5 MHz, CDCl3): δ 166.8, 165.8, 156.9, 132.6,
132.3, 129.4, 128.2, 111.3, 24.7. IR (cm-1): 2950, 1653, 1603,
1571, 1538, 1502. MS: 187.0 [M þ 1]þ.
NMR (250 MHz, DMSO): δ 13.26 (1H, br s), 8.45 (1H, s),
8.08-8.10 (2H, m), 7.50-7.63 (3H, m). 13C NMR (62.5 MHz,
DMSO þ TFA): δ 160.0, 158.0, 155.1, 132.9, 132.5, 129.6, 128.8,
112.1. IR (cm-1): 3042, 2952, 1648, 1603, 1559, 1535, 1498, 1466,
1016. MS: 251.0 [M þ 1, Br79]þ, 253.0 [M þ 1, Br81]þ.
Ethyl 4-oxo-2-phenyl-3,4-dihydropyrimidine-5-carboxylic acid
ester (10a).24 Eluent: PE:EA (3:1), then (1:1), then EA. Yield:
59%, white solid, mp 210 °C. 1H NMR (250 MHz, DMSO): δ
13.17 (1H, br s), 8.61 (1H, s), 8.15 (2H, d, J=7.5 Hz), 7.58 (3H,
m), 4.21 (2H, q, J=7.25 Hz), 1.25 (3H, t, J=7.25 Hz). 13C NMR
(62.5 MHz, DMSO): δ 163.9, 161.3, 160.1, 159.0, 133.0, 131.9,
129.1, 128.8, 115.0, 60.8, 14.5. IR (cm-1): 2976, 1707, 1655,
1567, 1538, 1509, 1446. MS: 245.0 [M þ 1]þ.
5-Bromo-2-thiophen-2-yl-3H-pyrimidin-4-one (12e). Eluent:
PE:EA (4:1). Yield: 58%, yellow solid, mp 227 °C dec. 1H
NMR (250 MHz, DMSO þ TFA) δ 9.24 (1H, br s), 8.32 (1H, s),
8.19 (1H, dd, J=1 Hz, 4 Hz), 7.88 (1H, dd, J=1 Hz, 5 Hz), 7.22
(1H, dd, J=4 Hz, 5 Hz). 13C NMR (62.5 MHz, DMSO þ TFA)
δ 159.0, 154.7, 152.8, 136.4, 133.5, 130.6, 129.2, 110.4. IR (cm-1):
1644, 1568, 1546, 1510, 1468, 1366, 1317, 897. MS: 321.0 [M þ Cu,
Br79]þ, 323.0 [M þ Cu, Br81]þ. HRMS (ESI): m/z calcd for
C8H5N2ONaSBr [M þ Na]þ 278.9204, found 278.9215.
6-Methyl-3-phenyl-4H-[1,2,4]triazin-5-one (11a).25 Eluent:
PE:EA (3:1), then EA. Yield: 67%, light yellow solid, mp
238-239 °C. 1H NMR (250 MHz, DMSO): δ 13.87 (1H, br s),
8.01-8.05 (2H, m), 7.54-7.68 (3H, m), 2.22 (3H, s). 13C NMR
(62.5 MHz, DMSO þ TFA): δ 163.1, {C(O)TFA: 160.2, 159.6,
Acknowledgment. We thank the French Chinese Founda-
tion for Science and Applications (FFCSA) and the China
Scholars Council (CSC) for financial support.
159.0, 158.3}, 158.8, 153.2, 133.4, 131.3, 129.8, 128.5, {F3CTFA
:
112.8, 118.2, 113.7, 109.1}, 18.0. IR (cm-1): 2847, 1604, 1543,
1488, 1436, 1373. MS: 188.0 [M þ 1]þ.
Supporting Information Available: Experimental proce-
dures and/or literature references for compounds 3d-g, 4, 5,
5-Bromo-2-phenyl-3H-pyrimidin-4-one (12a).26 Eluent: PE:
1
1
6, 7b, 7c, 7g, and 12 and H NMR and 13C NMR spectra for
EA (2:1). Yield: 70%, light yellow solid, mp 250-252 °C. H
compounds 3a-g, 6, 8a-12a, and 12e. This material is available
free of charge via the Internet at http://pubs.acs.org.
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