C-O and C-S coupling reaction of 1,2-di(pyrimidin-2-yl) disulfides with phenols/thiophenols promoted by copper(I) chloride

Article abstract of DOI:10.1002/hc.21397

An efficient protocol for C-O and C-S bonds formation by the cross-coupling reaction of 1,2-di(pyrimidin-2-yl) disulfides with phenols/thiophenols promoted by copper(I) chloride was established. It was discovered that variously substituted di(hetero)aryl disulfides and phenols were well tolerated. This strategy is the conversion of disulfides into hetero-aryl ethers and thioethers by a copper-promoted chemoselective C-S bond cleavage of disulfides.

Full text of DOI:10.1002/hc.21397

Received: 24 April 2017
DOI: 10.1002/hc.21397
Revised: 7 September 2017
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R E S E A R C H A R T I C L E
C-O and C-S coupling reaction of 1,2-di(pyrimidin-2-yl) disulfides
with phenols/thiophenols promoted by copper(I) chloride
Ping Zhang1
Yan Guo2
Zheng-Jun Quan2
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1School of Resource and Environmental
Science, Key Laboratory of Western
China’s Environmental Systems, Lanzhou
University, Lanzhou, China
2College of Chemistry and Chemical
Engineering, Northwest Normal University,
Lanzhou, Gansu, China
Abstract
An efficient protocol for C-O and C-S bonds formation by the cross-coupling reac-
tion of 1,2-di(pyrimidin-2-yl) disulfides with phenols/thiophenols promoted by
copper(I) chloride was established. It was discovered that variously substituted
di(hetero)aryl disulfides and phenols were well tolerated. This strategy is the conver-
sion of disulfides into hetero-aryl ethers and thioethers by a copper-promoted chem-
oselective C-S bond cleavage of disulfides.
Correspondence
Zheng-Jun Quan, College of Chemistry and
Chemical Engineering, Northwest Normal
University, Lanzhou, Gansu, China.
Email: quanzhengjun@hotmail.com
Di(hetero)aryl disulfides are widely used as electro-
philes instead of aryl halides for the construction of C-S
1
INTRODUCTION
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Diaryl ethers and thioethers are the ubiquitous scaffolds in
natural, pharmaceutical, agrochemical, and fine organic
chemicals, and particularly, heterobiaryl ether frameworks
containing a N-hetero-ring are found in pharmaceutically rel-
evant compounds such as Sorafenib, XK469, Tafenoquine,
and AMG900.
the small molecules approved by the U.S. Food and Drug
Administration (FDA) are heterocyclic and contain at least
1 nitrogen. Therefore, the discovery and development of new
synthetic methodologies for C-O and C-S bonds formation
have played an important role in organic chemistry.[2] Usually,
copper-catalyzed Ullmann reaction has been extensively used
for the synthesis of ethers involving phenols and aryl halides,
it often suffers from harsh reaction conditions such as higher
temperatures (>125-220°C), stronger bases.[3]
bond through S-S bond cleavage,[8] because that disul-
fides are structurally symmetrical, air stable, and easy
to handle.[9] Recently, we developed a series of method
to construct C-C, C-N, and C-S bonds through C-S and
S-S bonds cleavage of di(hetero)aryl disulfides with var-
ious nucleophiles including aryl boronic acids, alkynes,
Grignard reagents, and amines.[10] The obtained products
tetra-substituted pyrimidines display wide pharmacolog-
ical and biological properties[11] In continuation of our
work in the formation of the C-C and C-Z (Z = O, N, S)
bond utilizing 1,2-di(pyrimidin-2-yl) disulfide as an elec-
trophile, we investigated the C-O and C-S coupling of the
di(hetero)aryl disulfides with phenol and aryl thiol using
CuCl to obtain oxylated and sulfenylated pyrimidines
(Scheme 1).
[1]
It has been informed that one-half of
Transition metal-catalyzed C-O/C-S cross-coupling reaction
has become a significant methodology for the formation of ethers
andthioethersthroughthereactionofelectrophilicarylhalideswith
nucleophilic phenols/aryl thiols including the copper-mediated or
catalyzed Chan−Lam−Evans type Ar−B/Ar−OH couplings.[4]
In addition to the use of aryl halides, which synthesis
often involves tedious steps, harsh reaction conditions, and
waste production, sulfonates,[5] nitroarenes[6], aromatic es-
ters,[7] and others as alternative electrophiles were introduced
into the C-O cross-coupling chemistry.
We have reported the synthesis of 2-phenolic pyrimidines
by C-S and C-O cross-coupling reaction of pyrimidin-2-yl sul-
fonates with aryl thiols and phenols.[12] Alternatively, we have
developed an efficient preparation of 2-arylated pyrimidines
by the Mitsunobu reaction between 2-hydroxypyrimidine
[12b]
and phenols.
Compared pyrimidin-2-yl sulfonates from
Biginelli 3,4-dihydropyrimidine-2(1H)-ones via 2-step pro-
cedures of oxidation/esterification, di(hetero)aryl disulfides
were easily available from Biginelli 3,4-dihydropyrimidine-
2(1H)-thiones by one-step reaction.
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Heteroatom Chemistry. 2017;e21397.
https://doi.org/10.1002/hc.21397
wileyonlinelibrary.com/journal/hc
© 2017 Wiley Periodicals, Inc.
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Our previous work:
Ar1
Ar
R1
O
Ar2
N
N
O
N
N
S
N
EtO
EtO
R2
Me
Me
R1
R2
HN
Ar2B(OH)2
Cu(I)
Pd or Cu
Ar1
Ar
O
N
N
O
N
N
R
Ar2
S
RMgBr
ArB(OH)2
Pd, Cu
Ar
O
EtO
EtO
Fe(C5H5)2
N
N
Me
Me
S
Ar1
EtO
Me
O
Ar
RMgBr
R
2
O
N
EtO
Me
N
R
Pd, Ligand
Pd, Cu
Ar2XH
CuCl
EtO
N
N
This work
Me
R
Ar1
O
Ar2
N
X
=
EtO
Me
N
SCHEME 1 Synthesis of the
tetra-substituted pyrimidines from
1,2-di(pyrimidin-2-yl) disulfides
X
S, O
disulfides 1a and phenol 2a (Table 1). We found that CuCl
gave a good yield of the product 3a (61%) in the presence
of K3PO4 as a base; however, CuSO4·H2O/NaAsc system
only obtained 3a in a yield of 35%. Other tested conditions
could not obviously improve the reaction yield (entries
3-8). For examples, CuI and 2-OHPhCOOCu facilitated
the formation of product 3a albeit with low yield, respec-
tively (entries 3-4). No desired product was detected in the
2
RESULT AND DISCUSSION
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Recently, we reported that CuCl[10e] and Cu(OAc)2·H2O
(20 mol%)/NaAsc (30 mol%)[13] catalyst systems promoted
the C-N cross-coupling reaction of di(hetero)aryl disulfides
and aryl halides with amines or amides. So, we tested the
CuCl and CuSO4·H2O (100 mol%)/NaAsc (200 mol%) pro-
moter systems in the C-O coupling of 1,2-di(pyrimidin-2-yl)
TABLE 1 Optimization of reaction conditions for the C-O coupling of di(pyrimidin-2-yl) disulfide and phenola
1a
2a
3a
Entry
Cat. (eq.)
Base (equiv)
Temp. (oC)
Time (h)
Solvent
Yieldb (%)
1
2
3
4
5
6
7
8
9
CuSO4 (1.0)/NaAsc (2.0)
CuCl (1.0)
CuI (1.0)
o-OHC6H4COOCu (1.0)
-
CuCl (1.0)
CuCl (0.5)
CuCl (1.5)
CuCl (1.0)
CuCl (1.0)
K3PO4 (3.0)
K3PO4 (3.0)
K3PO4 (3.0)
K3PO4 (3.0)
K3PO4 (3.0)
K3PO4 (3.0)
K3PO4 (3.0)
K3PO4 (3.0)
K3PO4 (3.0)
K3PO4 (3.0)
80
80
80
80
80
80
80
80
140
140
12
12
12
12
12
24
12
12
12
24
Xylene
Xylene
Xylene
Xylene
Xylene
Dioxane
Xylene
Xylene
Xylene
Xylene
35
61
56
38
-
28
45
65
76
77
10
NaAsc = L-ascorbic acid sodium salt.
aCatalytic conditions: 1a (0.2 mmol), 2a (0.6 mmol), solvent (3 mL), under a N2 atmosphere.
bIsolated yield based on disulfide 1a (based on both pyrimidine groups from one molecule).

ZHANG et Al.
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absence of promoter, but the starting material 1a was re-
covered (entry 5). Lowering or enhancing the loading of
CuCl could not improve the obtained product (entries 7-8).
Notably, when the reaction was carried out at a high tem-
perature 140°C, the product 3a was isolated in 76%-77%
yield (entries 9-10).
To test the scope of the C-O coupling reaction, the
phenols 2a-h were reacted with 1a under the optimized
conditions (Scheme 2) and the yields of the obtained
products are shown in Scheme 2. In general, good yields
(67%-75%) of the desired products 3a-g were obtained
from phenols when the aryl group containing either an
electron-withdrawing (Cl, Br) or an electron-donating
(Me) group. However, moderate yield (37%) of the de-
sired ether derivative 3h was obtained when employed
2,4-dichlorophenol 2h.
Unfortunately, some limitations were noted in case of di-
aryl disulfides; such as 2,2′-dithiodipyridine and diphenyl
disulfide (treated with phenol 2a) were unreactive. Likewise,
the reaction of 1a with some strong electron-withdrawing
group-substituted phenols (nitrophenol) or alkyl alcohols such
as 2-propanol or benzyl alcohol were also failed to achieve
the desired product, but the starting materials were recovered
(Figure 1). Compared with the active 1,2-di(pyrimidin-2-yl)
disulfides, the diaryl disulfides were relatively unactive and
failed to coupling with phenol to give the corresponding
products.
Finally, we proposed a possible mechanism for the C-
O/C-S coupling reaction described in Scheme 4. It can be
informed that pyrimidine-containing disulfides are more ef-
ficient than aryl disulfides in the reaction due to the coordina-
tion of a soft basic N-atom to the copper salt promoting C-S
activation to give the intermediate A. Subsequently, the com-
plex A reacts with phenol producing the intermediate species
B, which subsequently undergoes reductive cleavage of the
C-S bond giving the C-O coupling product 3a. [10b-f]
To further expand the scope of the nucleophilic coupling
partners, we explored the C-S couplings of the disulfides 1
with 4-methoxybenzenethiol 4a. These C-S coupling reac-
tions smoothly proceeded under the optimal reaction con-
ditions to give the desired products (Scheme 3). Various
pyrimidine functionalized-disulfides (1a-f) were suitable
partners for the coupling reaction giving the C-S cross-
coupling products (5a-g) in good yields. Notably, cou-
plings of 4-fluoro-, 4-chloro-, 4-bromo-, 4-methyl-, and
4-nitrophenyl substituted disulfides proceeded with 4a
to yield the C-S coupling products in good yields (5a-g).
The process also tolerated a variety of steric and electronic
changes to thiophenols such as 4-chloro-, 4-bromo-, and
4-methyl-substituted thiophenols to deliver the products 5h-i
in good yields of 52%-59%.
3
CONCLUSIONS
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In summary, we developed an efficient method for C-O and
C-S cross-coupling reaction of 1,2-di(pyrimidin-2-yl) di-
sulfides with phenols and thiophenols via Cu-promoted C-S
bond cleavage of disulfides. The use of promoter CuCl was
necessary for efficient formation of the C-O and C-S bond in
this reaction in a homogeneous system heightens the overall
efficiency of the given synthesis.
SCHEME 2 Scope of disulfides
(1a) and phenol in the C-O cross-coupling
reaction

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SCHEME 3 Scope of disulfides (1a)
and thiophenol in the C-S cross-coupling
reaction
(0.6 mmol) were added to an oven-dried Schlenk tube. The
tube was stoppered and degassed with nitrogen 3 times.
Water-free xylene (3 mL) was added by syringe, and the mix-
ture was stirred for 12 hours at 140°C, and the reaction was
monitored by TLC analysis. Then, the reaction was quenched
by adding into NH4Cl aqueous and extracted with ethyl ace-
tate (3 × 20 mL). The combined organic layers were washed
with aqueous NH4Cl, NaOH (5%), and then brine, dried over
MgSO4, filtered, and the volatiles were removed in vacuum.
The residue was purified by column chromatography on sil-
ica gel (ethyl acetate/petroleum ether 1:30) to give the cor-
responding products.
FIGURE 1 Limitations of the C-O coupling of disulfides with
alcohols. Reaction conditions are those of Table 1
4.2
Ethyl 4-methyl-2-phenoxy-6-
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phenylpyrimidine-5-carboxylate (3a)
4
EXPERIMENTAL
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1
Colorless oil; H NMR (600 MHz, CDCl3) δ = 7.59 (d,
4.1
General procedure for the synthesis of
|
J = 7.2 Hz, 2H), 7.46-7.36 (m, 5H), 7.27-7.20 (m, 3H),
4.18 (q, J = 7.2 Hz, 2H), 2.57 (s, 3H), 1.06 (t, J = 7.2 Hz,
3H) ppm. 13C NMR (150 MHz, CDCl3) δ = 169.14, 168.05,
166.59, 163.94, 152.82, 137.30, 130.26, 129.33, 128.39,
C-S coupling products
Under an atmosphere of nitrogen, disulfide 1a (0.2 mmol),
phenol 2a (0.6 mmol), CuCl (0.2 mmol), and K3PO4
SCHEME 4 Possible mechanism for
the C-O coupling reaction of disulfide 1a
with phenol 2a
(A)
(B)

ZHANG et Al.
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128.35, 125.17, 121.56, 121.04, 77.24, 77.03, 76.82, 61.77,
4.7
Ethyl 2-(4-chlorophenoxy)-4-methyl-6-
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22.73, 13.60 ppm. EI-MS: m/z = 334 (M+).
phenylpyrimidine-5-carboxylate (3f)
1
Colorless oil; H NMR (400 MHz, CDCl3) δ = 7.58 (d,
4.3
Ethyl 4-methyl-6-phenyl-2-(4-tolyloxy)
|
J = 8.0 Hz, 2H, ArH), 7.44-7.34 (m, 5H, ArH), 7.18 (d,
J = 8.0 Hz, 2H, ArH), 4.17 (q, J = 8.0 Hz, 2H, CH2), 2.56 (s,
3H, CH3), 1.05 (t, J = 8.0 Hz, 3H, CH3); 13C NMR (100 MHz,
CDCl3) δ = 169.05, 167.68, 166.48, 163.43, 151.10, 136.92,
130.26, 130.19, 129.20, 129.07, 128.25, 128.12, 122.77,
121.15, 116.57, 61.65, 22.47, 13.39. EI-MS: m/z = 368 (M+);
Anal. Calcd for C20H17ClN2O3: C, 65.13; H, 4.65; N, 7.60.
Found: C, 65.07; H, 4.60; N, 7. 61.
pyrimidine-5-carboxylate (3b)
1
Colorless oil; H NMR (600 MHz, CDCl3) δ = 7.59 (d,
J = 7.2 Hz, 2H), 7.45-7.39 (m, 3H), 7.20 (d, J = 8.4 Hz, 2H),
7.12 (d, J = 8.4 Hz, 2H), 4.17 (q, J = 7.2 Hz, 2H), 2.56 (s,
3H), 2.37 (s, 3H), 1.06 (t, J = 7.2 Hz, 3H) ppm. 13C NMR
(150 MHz, CDCl3) δ = 169.07, 168.10, 166.61, 164.06,
150.57, 137.37, 134.68, 130.21, 129.83, 128.37, 128.35,
121.21, 120.92, 77.20, 76.98, 76.77, 61.74, 22.73, 20.88,
13.59 ppm. EI-MS: m/z = 348 (M+).
4.8
Ethyl 2-(2-chlorophenoxy)-4-methyl-6-
|
phenylpyrimidine-5-carboxylate (3g)
4.4
Ethyl 4-methyl-6-phenyl-2-(3-tolyloxy)
Colorless oil; 1H NMR (400 MHz, CDCl3) δ = 7.49 (d,
J = 4.0 Hz, 2H, ArH), 7.38-7.27 (m, 4H, ArH), 7.20-7.06 (m,
2H, ArH), 7.11-7.07 (m, 1H, ArH), 4.09 (q, J = 8.0 Hz, 2H,
CH2), 2.47 (s, 3H, CH3), 0.97 (t, J = 8.0 Hz, 3H, CH3); 13C
NMR (100 MHz, CDCl3) δ = 169.21, 167.91, 166.50, 163.27,
148.88, 137.15, 130.28, 128.32, 128.30, 127.70, 127.33, 126.44,
123.70, 121.24, 61.73, 22.64, 13.55. EI-MS: m/z = 368 (M+);
Anal. Calcd for C20H17ClN2O3: C, 65.13; H, 4.65; N, 7.60.
Found: C, 65.08; H, 4.61; N, 7.62. HRMS (ESI): calculated for
C20H17ClN2O3: [M+H]+ 369.1000; found: 369.0998.
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pyrimidine-5-carboxylate (3c)
1
Colorless oil; H NMR (600 MHz, CDCl3) δ = 7.61-7.59
(m, 2H), 7.44-7.39 (m, 3H), 7.28 (t, J = 7.8 Hz, 1H), 7.04 (d,
J = 7.8 Hz, 2H), 4.18 (q, J = 7.2 Hz, 2H), 2.57 (s, 3H), 2.38
(s, 3H), 1.06 (t, J = 7.2 Hz, 3H) ppm. 13C NMR (150 MHz,
CDCl3) δ = 169.11, 168.10, 166.63, 164.01, 152.76, 139.50,
137.32, 130.25, 129.00, 128.39, 128.35, 125.97, 122.04,
120.98, 118.52, 77.21, 77.00, 76.79, 61.79, 22.71, 21.38,
13.60 ppm. EI-MS: m/z = 348 (M+).
4.9
Ethyl 2-(2,4-dichlorophenoxy)-4-
4.5
Ethyl 4-methyl-6-phenyl-2-(2-tolyloxy)
|
|
methyl-6-phenylpyrimidine-5-carboxylate (3h)
pyrimidine-5-carboxylate (3d)
1
Yellow oil; 1H NMR (400 MHz, CDCl3) δ = 7.57 (d,
J = 8.0 Hz, 2H, ArH), 7.46-7.37 (m, 2H, ArH), 7.28-7.22 (m,
2H, ArH), 7.18-7.11 (m, 2H, ArH), 4.18 (q, J = 8.0 Hz, 2H,
CH2), 2.55 (s, 3H, CH3), 2.22 (s, 3H, CH3), 1.06 (t, J = 8.0 Hz,
3H, CH3); 13C NMR (100 MHz, CDCl3) δ = 169.14, 168.15,
166.62, 163.87, 151.35, 137.34, 131.10, 130.55, 130.21,
128.37, 128.35, 126.80, 125.44, 121.86, 120.82, 61.76,
22.74, 16.44, 13.61; EI-MS: m/z = 348 (M+); Anal. Calcd
for C21H20N2O3: C, 72.40; H, 5.79; N, 8.04. Found: C, 72.37;
H, 5.75; N, 8. 02.
White solid, m.p. = 88-89°C. H NMR (600 MHz, CDCl3)
δ = 7.56 (d, J = 7.8 Hz, 2H), 7.47 (s, 1H), 7.44 (t, J = 6.8 Hz,
1H), 7.39 (t, J = 7.6 Hz, 2H), 7.27 (d, J = 9.0 Hz, 1H), 7.19
(d, J = 8.4 Hz, 1H), 4.17 (q, J = 7.2 Hz, 2H), 2.55 (s, 3H),
1.05 (t, J = 7.2 Hz, 3H) ppm. 13C NMR (150 MHz, CDCl3)
δ = 169.40, 167.86, 166.63, 163.02, 147.64, 137.01, 131.28,
130.38, 130.13, 128.43, 128.33, 127.96, 124.60, 121.52, 77.21,
77.00, 76.79, 61.87, 22.70, 13.60 ppm. EI-MS: m/z = 402
(M+), 404 (M + 2).
4.10
Ethyl 2-(4-methoxyphenylthio)-4-
|
4.6
Ethyl 2-(4-bromophenoxy)-4-methyl-6-
methyl-6-phenylpyrimidine-5-carboxylate (5a)
|
phenylpyrimidine-5-carboxylate (3e)
Orange oil; 1H NMR (400 MHz, CDCl3) δ = 7.46 (q,
J = 8.0 Hz, 4H, ArH), 7.29 (t, J = 8.0 Hz, 3H, ArH), 6.87
(d, J = 12.0 Hz, 2H, ArH), 4.05 (q, J = 8.0 Hz, 2H, CH2),
3.76 (s, 3H, CH3), 2.42 (s, 3H, CH3), 0.96 (t, J = 8.0 Hz,
3H, CH3); 13C NMR (100 MHz, CDCl3) δ = 172.67, 168.09,
165.78, 163.46, 160.41, 137.37, 136.91, 130.06, 128.34,
128.29, 121.27, 121.27, 114.48, 109.71, 61.67, 55.30,
22.57, 13.56. EI-MS: m/z = 380 (M+); Anal. Calcd for
C21H20N2O3S: C, 66.29; H, 5.30; N, 7.36. Found: C, 66.22;
H, 5.28; N, 7. 33.
Colorless oil; 1H NMR (600 MHz, CDCl3) δ = 7.58
(d, J = 7.2 Hz, 2H), 7.50 (d, J = 9.0 Hz, 2H), 7.45
(t, J = 7.4 Hz, 1H), 7.40 (t, J = 7.4 Hz, 2H), 7.13 (d,
J = 8.4 Hz, 2H), 4.18 (q, J = 7.2 Hz, 2H), 2.57 (s, 3H),
1.06 (t, J = 7.2 Hz, 3H) ppm. 13C NMR (150 MHz, CDCl3)
δ = 169.28, 167.92, 166.73, 163.52, 151.79, 137.04, 132.35
(d, J = 19.7 Hz), 130.45, 128.49, 128.31, 123.41, 121.38,
118.19, 117.29, 61.92, 22.67, 13.60. EI-MS: m/z = 412
(M+), 414 (M + 2).

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143.48, 136.95, 129.39, 123.42, 121.36, 119.50, 114.60,
62.00, 55.33, 22.76, 13.66; EI-MS: m/z = 425 (M+); Anal.
Calcd for C21H19N3O5S: C, 59.28; H, 4.50; N, 9.88. Found:
C, 59.22; H, 4.47; N, 9. 86.
4.11
Ethyl 4-(4-fluorophenyl)-2-(4-
|
methoxyphenylthio)-6-methylpyrimidine-5-
carboxylate (5b)
Yellow oil; 1H NMR (400 MHz, CDCl3) δ = 7.54 (t,
J = 8.0 Hz, 4H, ArH), 7.05 (t, J = 8.0 Hz, 2H, ArH), 6.95 (d,
J = 8.0 Hz, 2H, ArH), 4.19 (q, J = 8.0 Hz, 2H, CH2), 3.84 (s,
3H, CH3), 2.50 (s, 3H, CH3), 1.10 (t, J = 8.0 Hz, 3H, CH3);
13C NMR (100 MHz, CDCl3) δ = 172.78, 168.04, 165.88,
162.15, 160.51, 136.96, 130.55, 130.46, 121.06, 115.53,
115.32, 114.52, 61.77, 55.32, 31.89, 22.57, 13.67. EI-MS:
m/z = 398 (M+); Anal. Calcd for C21H19FN2O3S: C, 63.30;
H, 4.81; N, 7.03. Found: C, 63.27; H, 4.79; N, 7.01.
4.15
Ethyl 2-(4-methoxyphenylthio)-4-
|
methyl-6-p-tolylpyrimidine-5-carboxylate (5f)
1
Colorless oil; H NMR (400 MHz, CDCl3) δ = 7.55 (d,
J = 12.0 Hz, 2H, ArH), 7.42 (d, J = 8.0 Hz, 2H, ArH), 7.16
(d, J = 8.0 Hz, 2H, ArH), 6.94 (d, J = 8.0 Hz, 2H, ArH),
4.19 (q, J = 8.0 Hz, 2H, CH2), 3.85 (s, 3H, CH3), 2.49 (s,
3H, CH3), 2.36 (s, 3H, CH3), 1.10 (t, J = 8.0 Hz, 3H, CH3);
EI-MS: m/z = 394 (M+); Anal. Calcd for C22H22N2O3S: C,
66.98; H, 5.62; N, 7.10. Found: C, 66.96; H, 5.60; N, 7.08.
4.12
Ethyl 4-(4-chlorophenyl)-2-(4-
|
methoxyphenylthio)-6-methylpyrimidine-5-
carboxylate (5c)
4.16
Ethyl 4-methyl-6-phenyl-2-(4-
|
tolylthio)pyrimidine-5-carboxylate (5g)
1
White solid, m.p. 35-37°C; H NMR (400 MHz, CDCl3)
1
δ = 7.53 (d, J = 8.0 Hz, 2H, ArH), 7.46 (d, J = 8.0 Hz, 2H,
ArH), 7.34 (d, J = 8.0 Hz, 2H, ArH), 6.95 (d, J = 12.0 Hz,
2H, ArH), 4.19 (q, J = 8.0 Hz, 2H, CH2), 3.85 (s, 3H, CH3),
2.50 (s, 3H, CH3), 1.11 (t, J = 8.0 Hz, 3H, CH3); 13C NMR
(100 MHz, CDCl3) δ = 172.89, 167.90, 165.98, 162.08,
160.50, 136.95, 136.44, 129.73, 128.57, 121.06, 119.89,
114.50, 61.81, 55.31, 31.88, 22.59, 13.66. EI-MS: m/z = 414
(M+); Anal. Calcd for C21H19ClN2O3S: C, 60.79; H, 4.62; N,
6.75. Found: C, 60.73; H, 4.58; N, 6. 69.
White solid, m.p. = 64-66°C. H NMR (600 MHz, CDCl3)
δ = 7.52 (d, J = 8.0 Hz, 4H), 7.41 (t, J = 7.2 Hz, 1H), 7.36 (t,
J = 7.8 Hz, 2H), 7.21 (d, J = 8.4 Hz, 2H), 4.15 (q, J = 7.2 Hz,
2H), 2.49 (s, 3H), 2.39 (s, 3H), 1.04 (t, J = 7.2 Hz, 3H) ppm.
13C NMR (100 MHz, CDCl3): δ = 172.33, 168.04, 165.76,
163.46, 139.10, 137.37, 135.03, 130.02, 129.6, 128.30,
125.88, 121.34, 61.64, 22.54, 21.28, 13.55 ppm. EI-MS:
m/z = 364 (M+).
4.17
Ethyl 2-((4-chlorophenyl)thio)-4-
|
4.13
Ethyl 4-(4-bromophenyl)-2-(4-
methyl-6-phenylpyrimidine-5-carboxylate (5h)
|
methoxyphenylthio)-6-methylpyrimidine-5-
carboxylate (5d)
1
White solid, m.p. = 41-43°C. H NMR (400 MHz, CDCl3):
δ = 7.49 (d, J = 8.0 Hz, 2H), 7.44 (d, J = 7.6 Hz, 2H), 7.35-
7.30 (m, 5H), 4.08 (q, J = 7.2 Hz, 2H), 2.43 (s, 3H), 0.97 (t,
J = 7.0 Hz, 3H) ppm. 13C NMR (100 MHz, CDCl3): δ = 171.66,
168.14, 166.26, 163.90, 137.47, 136.66, 135.58, 130.47, 129.34,
128.64, 128.57, 128.27, 121.98, 77.58, 77.27, 76.95, 62.02,
22.80, 13.84 ppm. EI-MS: m/z = 384 (M+), 386 (M + 2).
1
Colorless oil; H NMR (400 MHz, CDCl3) δ = 7.55-7.44
(m, 6H, ArH), 6.73 (d, J = 8.0 Hz, 2H, ArH), 4.13 (q,
J = 8.0 Hz, 2H, CH2), 3.69 (s, 3H, CH3), 2.52 (s, 3H, CH3),
1.04 (t, J = 8.0 Hz, 3H, CH3); 13C NMR (100 MHz, CDCl3)
δ = 171.10, 167.54, 166.43, 162.83, 160.27, 136.11, 133.69,
131.69, 130.02, 127.20, 125.04, 122.25, 114.51, 61.97,
55.30, 22.59, 13.65. EI-MS: m/z = 458 (M+); Anal. Calcd for
C21H19BrN2O3S: C, 54.91; H, 4.17; N, 6.10. Found: C, 54.87;
H, 4.12; N, 5.98.
4.18
Ethyl 2-((4-bromophenyl)thio)-4-
|
methyl-6-phenylpyrimidine-5-carboxylate (5i)
1
White solid, m.p. = 59-61°C. H NMR (400 MHz, CDCl3):
δ = 7.41 (d, J = 5.6 Hz, 6H), 7.28 (d, J = 7.2 Hz, 3H), 4.05 (d,
J = 7.2 Hz, 2H), 2.40 (s, 3H), 0.93 (t, J = 7.2 Hz, 3H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 171.24, 167.86, 166.00, 163.63,
137.20, 136.58, 136.39, 132.02, 130.20, 129.07, 128.67,
128.38, 128.31, 123.53, 121.75, 77.32, 77.00, 76.68, 61.74,
22.53, 13.57 ppm. EI-MS: m/z = 428 (M+), 430 (M + 2).
4.14
Ethyl 2-(4-methoxyphenylthio)-
|
4-methyl-6-(4-nitrophenyl)pyrimidine-5-
carboxylate (5e)
Yellow oil; 1H NMR (400 MHz, CDCl3) δ = 8.23 (d,
J = 8.0 Hz, 2H, ArH), 7.67 (d, J = 8.0 Hz, 2H, ArH), 7.53
(d, J = 8.0 Hz, 2H, ArH), 6.96 (d, J = 8.0 Hz, 2H, ArH),
4.19 (q, J = 8.0 Hz, 2H, CH2), 3.86 (s, 3H, CH3), 2.54 (s, 3H,
CH3), 1.09 (t, J = 8.0 Hz, 3H, CH3); 13C NMR (100 MHz,
CDCl3) δ = 173.45, 167.26, 166.56, 161.25, 160.64, 148.60,
ORCID
Zheng-Jun Quan
http://orcid.org/0000-0002-4393-3594

ZHANG et Al.
7 of 7
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How to cite this article: Zhang P, Guo Y, Quan Z-J.
C-O and C-S coupling reaction of 1,2-di(pyrimidin-
2-yl) disulfides with phenols/thiophenols promoted
by copper(I) chloride. Heteroatom Chem.
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