Base-Mediated Three-Component Tandem Reactions for the Synthesis of Multisubstituted Pyrimidines

Article abstract of DOI:10.1021/acs.joc.7b02113

A base-mediated three-component tandem reaction for the synthesis of multisubstituted pyrimidines from amidines, aryl alkynes, and aldehydes in a one-pot manner has been developed. Advantages of this transformation include being transition-metal-free, high efficiency, available starting materials, and being environmentally friendly.

Full text of DOI:10.1021/acs.joc.7b02113

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Note
Base-Mediated Three-Component Tandem Reactions
for the Synthesis of Multi-Substituted Pyrimidines
Dongqing Liu, Wei Guo, Wanqing Wu, and Huanfeng Jiang
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.7b02113 • Publication Date (Web): 21 Nov 2017
Downloaded from http://pubs.acs.org on November 22, 2017
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Base-Mediated Three-Component Tandem Reactions for the Synthesis of Multi-
Substituted Pyrimidines
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Dongqing Liu,a,c Wei Guo,a,b,c Wanqing Wu,a,* Huanfeng Jianga,*
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a Key Laboratory of Functional Molecular Engineering of Guangdong Province,
School of Chemistry and Chemical Engineering, Key Laboratory of Functional
Molecular Engineering of Guangdong Province, South China University of
Technology, Guangzhou 510640, China
Fax: (+86) 20ꢀ8711ꢀ2906; Eꢀmail: cewuwq@scut.edu.cn, jianghf@scut.edu.cn
b Key Laboratory of Organoꢀpharmaceutical Chemistry of Jiangxi Province, Gannan
Normal University, Ganzhou 341000, China
c D. Liu and W. Guo contributed equally.
ABSTRACT: Base mediated threeꢀcomponent tandem reaction for the synthesis of
multiꢀsubstituted pyrimidines from amidines, aryl alkynes and aldehydes in a oneꢀpot
manner has been developed. This transformation features transitionꢀmetal free, high
efficiency, available starting materials and environmentally friendly advantage.
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Pyrimidines represent one of the most important heterocycles in biologically active
molecules, naturally products, and functional materials.1 Notably, much attention has
been directed toward the pyrimidines with biological activities, including antiꢀcancer,
antiꢀinflammatory, antiꢀmycobacterial, antibacterial and antimalarial.2 In addition,
pyrimidines can be used as potential candidates for photophysical materials,
especially light emitting devices.3 Although a number of methods have been
developed for the preparation of pyrimidines,4 most of them are mainly confined to
expensive and moisture sensitive reagents,5 use multistep reactions,6 microwave
irradiation,7 transition metal catalysts8 and unavailable starting materials.9 Despite an
appealing synthetic strategy, the design and development of novel domino reactions
for the acquisition of pyrimidines from easily available starting materials under green
conditions continues to be a challenge.10
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Sequential tandem oneꢀpot reactions with two or more components have emerged
as one of the powerful tools in organic synthesis for the construction of the diversity
and complexity of the compound library, which shows high synthetic efficiency and
atomꢀeconomic advantages.11 The commonly devised strategy for tandem reactions
involves two or more separated functional groups in the participants, of which one
functionality is initiated in the first process and then the others are sequentially
subjected to the next process.12 Recently, threeꢀcomponent tandem reactions of 2ꢀ
aminopyridine, aldehydes and alkynes have been developed with copper as catalyst
for the preparation of imidazo[1,2ꢀa]pyridines.13 This prompted us to design a new
tandem reaction route to multiꢀsubstituted pyrimidines through the aminationꢀ
cyclizationꢀoxidation process from amidines, aryl alkynes and aldehydes in a oneꢀpot
manner.
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Table 1. Selected optimization studiesa
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Entry
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Base
DBU
DABCO
Et3N
K3PO4
KOH
tꢀBuOK
tꢀBuOK
tꢀBuOK
tꢀBuOK
tꢀBuOK
tꢀBuOK
tꢀBuOK
tꢀBuOK
tꢀBuOK
ꢀ
Solvent
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
Toluene
CH3CN
DMF
T (oC)
120
120
120
120
120
120
120
80
120
120
100
80
100
120
120
120
120
120
Yield (%)b
36
26
24
30
55
62
21
47
25
9
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16c
17d
18e
DMA
1,4ꢀDioxane
44
31
DCE
EtOH
H2O
DMSO
DMSO
DMSO
DMSO
n.d.
n.d.
n.d.
trace
73
50
55
tꢀBuOK
tꢀBuOK
tꢀBuOK
aReaction conditions: Unless otherwise noted, all reactions were performed with 1a (0.20 mmol), 2a (0.30 mmol),
b
3a (0.30 mmol), and base (0.40 mmol) in 1.0 mL solvent under air for 12 h. n.d. = not detected. GC yield based
on 1a with nꢀdodecane as an internal standard. cUnder N2. dUnder O2. eVacuum protection.
Initially, we began our investigation with easily accessible benzimidamide (1a),
ethynylbenzene (2a) and 2,4ꢀdimethylbenzaldehyde (3a) as the model substrates to
test the feasibility of our projected transformation process by our previous reports.
(Table 1). A preliminary attempt with DBU as base in 1.0 mL DMSO at 120 oC led to
4ꢀ(2,4ꢀdimethylphenyl)ꢀ2,6ꢀdiphenylpyrimidine (4aaa) in 36% yield (Table 1, entry
1). Next, using DABCO, Et3N, and K3PO4 as bases, the yields were still not further
increased (Table 1, entries 2ꢀ4). To our delight, KOH and tꢀBuOK exhibited superior
reactivities affording the yields of 55% and 62%, respectively (Table 1, entries 5ꢀ6).
Different solvents such as toluene, CH3CN, DMF, DMA, and 1,4ꢀdioxane have been
explored, however, they did not enhance the yield of the target product, and DCE,
EtOH and H2O were completely ineffective (Table 1, entries 7ꢀ14). Whereas the
absence of tꢀBuOK inhibited the reaction performance (Table 1, entry 15).
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Encouragingly, when the reaction was performed under N2 atmosphere, 4aaa was
afforded in 73% yield (Table 1, entry 16). However, the lower yield of 4aaa was
obtained under O2 atmosphere or vacuum (Table 1, entries 17 and 18). As a
consequence, the optimized reaction conditions were comfirmed by using tꢀBuOK
(0.40 mmol) in DMSO at 120 oC under N2 (1 atm) for 12 h.
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Table 2. Substrate scope of amidinesa
aReaction conditions: Unless otherwise noted, all reactions were performed with 1 (0.2 mmol), 2a (0.30 mmol), 3a
(0.30 mmol), tꢀBuOK (0.40 mmol) in 1.0 mL solvent under N2 at 120 oC for 12 h. bYields of isolated products.
Next, the scope and generality of this process were investigated under the
optimized conditions. We firstly investigated the scope of different substituted
amidines with ethynylbenzene (2a) and 2, 4ꢀdimethylbenzaldehyde (3a) as partners.
The results are summarized in Table 2. Generally, arylamidines bearing either
electronꢀdonating or electronꢀwithdrawing groups are efficient substrates, providing
the desired products 4aaa–4kaa in moderate yields. orthoꢀSubstituted arylamidines
gave slightly lower yields because of the steric effects. It is worth noting that halogen
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groups (Cl, Br) were tolerated, providing the possibility for further functionalization
(4daa, 4faa, 4iaa, 4kaa). Nonꢀaromatic amidines were also tolerated well, delivering
the desired products 4laa–4oaa in moderate yields. Gratifyingly, isonicotinamidine
could also be transformed in combination with 2a and 3a into the desired products
(4paa) in moderate yields upon isolation.
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Table 3. Substrate scope of aryl alkynesa
aReaction conditions: Unless otherwise noted, all reactions were performed with 1a (0.2 mmol), 2 (0.30 mmol), 3a
(0.30 mmol), tꢀBuOK (0.40 mmol) in 1.0 mL solvent under N2 at 120 oC for 12 h. bYields of isolated products.
After having exhibited a broad scope for substituted amidines, a series of
structurally diverse aryl alkynes 2 were next investigated to react with 1a and 3a
under the same optimized conditions. As shown in Table 3, alkyne derivatives bearing
different substitution patterns including F, Cl, CF3, C5H11, CH3 and OCH3 were found
to be well tolerated and smoothly gave the desired products in moderate yields (4aba–
4aka). The experimental results also showed that strong electronꢀdonating groups on
the aromatic ring seemed to promote the reaction reactivity slightly, and halide
substituents unfavored the formation of products 4. Moreover, paraꢀ andmetaꢀ
substituted aryl alkynes gave higher yields than those of orthoꢀsubstituted substrates.
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In addition, 2ꢀethynylpyridine and 3ꢀethynylthiophene were found to be compatible
and converted to the corresponding products 4ala and 4ama. Nonetheless, when the
alkyne was used as the substrates, only a trace amount of the corresponding products
could be detected.
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Table 4. Substrate scope of aryl aldehydesa
aReaction conditions: Unless otherwise noted, all reactions were performed with 1a (0.2 mmol), 2a (0.30 mmol), 3
(0.30 mmol), tꢀBuOK (0.40 mmol) in 1.0 mL solvent under N2 at 120 oC for 12 h. bYields of isolated products.
Furthermore, we examined the scope of aryl aldehydes using 1a and 2a as coupling
partners. As shown in Table 4，Benzaldehydes bearing electronꢀdonating or electronꢀ
withdrawing groups produced the desired products with moderate yields (4aab–4aai).
Substituents such as ꢀCH3, ꢀOCH3, ꢀC(CH3)3 and other functionalities (F, Cl) on the
aryl ring of 3 were well tolerated, and the electronic property of which affected the
product yields to some extent. Specifically, electronꢀrich ones afforded better results
than those of electronꢀdeficient ones. Notably, heteroaryl aldehydes were also used as
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effective coupling partner to afford the corresponding products in fair yields (4aaj,
4aak, 4aal). Satisfactorily, 1ꢀmethylꢀ1Hꢀpyrrole also transformed effectively into our
desired product 4aam in 74% yeild. Much to our delight, substrate with naphthalene
was successfully subjected to this reaction system providing 4aan. However,
alkylaldehyde only generated a trace of products.
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Scheme 1. Application of the pyrimidines products
The pyrimidine of our developed protocol can smoothly proceed the further
transformation, which is illustrated in Scheme 1. The Suzuki coupling reaction
between 4iag and 5 successfully provided the corresponding product 6 in good yield.
In addition, the product 6 could further transfer to some compounds for an organic
optoelectric device, indicating that pyrimidines have potential applications in light
emitting devices.14
In order to gain more insight into the reaciton mechanism, control experiments
were further conducted. In the presence of TEMPO under the standard reaction
conditions, 4aaa was also obtained. These results suggested that a radical pathway
should not be involved (Scheme 2, a). Furthermore, when 1a was reacted with
propargylic alcohol 7 under the same conditions, the desired product 4aag was
obtained in 60% yield, indicating that 7 might be a reasonable intermediate for this
chemical process (Scheme 2, b).
Scheme 2. Mechanistic studies
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Based on the above experimental results in the current study and previous reports,13,
15a nonꢀradical pathway mechanism was proposed (Scheme 3). Firstly,
ethynylbenzene 2a reacts with aldehyde 3g to deliver propargylic alcohol 7.
Intermediate 7 reacts with benzimidamide (1a) to generate intermediate 8, and then
further affords the intermediate 9 through intramolecule addition process. Finally, as a
result of the oxidability of DMSO ,the oxidation of 9 gives the product 4aag.16
Scheme 3. Possible reaction mechanism
In conclusion, this protocol realizes a base mediated threeꢀcomponent tandem
reaction for the synthesis of multiꢀsubstituted pyrimidines from amidines, aryl alkynes
and aldehydes in oneꢀpot. This novel transformation provides a practical approach for
the synthesis of a variety of pyrimidines, showing stepꢀeconomy, wide substrate scope,
good functional group tolerance and mild reaction conditions, which exhibits potential
applications in the pharmaceutical industry and material field.
EXPERIMENTAL SECTION
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General Information. Melting points were measured using a melting point
instrument and are uncorrected. 1H and 13CNMR spectra were recorded on a 400 MHz
NMR spectrometer (Bruker Avance DRXꢀ400 MHz). IR spectra were obtained with
an infrared spectrometer on either potassium bromide pellets or liquid films between
two potassium bromide pellets (Bruker Tensor 27). GC−MS (Thermo Trace 1300
GC−Thermo ISO LT) data were obtained using electron ionization. HRMS (MAT
95XP, Thermo) was carried out on a highꢀresolution mass spectrometer (LCMSꢀITꢀ
TOF). TLC was performed using commercially available 100−400 mesh silica gel
plates (GF254). Unless otherwise noted, purchased chemicals were used without
further purification.
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General Procedure for the Synthesis of Pyrimidine Derivatives. A mixture of
amidines (0.20 mmol), ethynylbenzene (0.30 mmol) and aldehyde (0.30 mmol),
tꢀBuOK (0.40 mmol, 2.0 equiv) was stirred in DMSO (1.0 mL) at 120 oC under an N2
(1 atm) atmosphere for 12 h. After completion of the reaction (monitored by TLC),
water (10 mL) was added to the reaction mixture, and the resulting mixture was
extracted with ethyl acetate. The combined organic layers were then dried over
MgSO4, filtered, and then concentrated in vacuum. The residue was purified by flash
chromatography on silica gel to give the desired product (using the mixture of
petroleum ether and ethyl acetate as eluents).
4-(2,4-Dimethylphenyl)-2,6-diphenylpyrimidine (4aaa). Using a mixture of
petroleum etherꢀethyl acetate (200:1) as eluent. Pale yellow solid: 73% yield (49 mg);
1
mp 73−75 °C; IR (KBr, cmꢀ1): ν 2922, 1630, 1520, 1384, 1120, 772; H NMR (400
MHz, CDCl3, ppm): δ 8.75 (d, J = 8.0 Hz, 2H), 8.32 (d, J = 8.0 Hz,2H), 7.77 (s, 1H),
7.62ꢀ7.55 (m, 7H), 7.22 (d, J = 8.0 Hz, 2H), 2.62 (s, 3H), 2.45 (s, 3H); 13C NMR (100
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MHz, CDCl3, ppm): δ 168.2, 164.1, 164.0, 139.5, 138.3, 137.5, 136.5, 135.9, 132.2,
130.8, 130.7, 129.8, 129.0, 128.6, 128.5, 127.3, 127.0, 114.32, 21.3, 20.9; MS (EI, 70
eV) m/z 336.35, 259.28, 232.24, 104.14, 77.12; HRMS (ESI) calcd C24H20N2Na [M +
Na]+ m/z 359.1519, found m/z 359.1523.
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4-(2,4-Dimethylphenyl)-6-phenyl-2-(p-tolyl)pyrimidine (4baa). Using a mixture of
petroleum etherꢀethyl acetate (200:1) as eluent. Yellow oil: 67 % yield (47 mg); IR
(KBr, cmꢀ1): ν 2920, 1568, 1520, 1453, 1368, 1097, 767; 1H NMR (400 MHz, CDCl3,
ppm): δ 8.56 (d, J = 8.0 Hz, 2H), 8.28ꢀ8.25 (m, 2H), 7.70 (s, 1H), 7.56ꢀ7.51 (m, 4H),
7.32 (d, J = 8.0 Hz, 2H), 7.18 (d, J =12.0 Hz, 2H), 2.56 (s, 3H), 2.45 (s, 3H), 2.42 (s,
13
3H); C NMR (100 MHz, CDCl3, ppm): δ 168.1, 164.1, 164.0, 140.8, 139.4, 137.6,
136.5, 135.9, 135.5, 132.1, 130.7, 129.7, 129.2, 128.9, 128.5, 127.3, 126.9, 114.0,
21.6, 21.3, 20.8; MS (EI, 70 eV) m/z 350.38, 273.29, 232.26, 154.16, 77.13; HRMS
(ESI) calcd C25H23N2 [M + H]+ m/z 351.1856, found m/z 351.1860.
4-(2,4-Dimethylphenyl)-2-(4-fluorophenyl)-6-phenylpyrimidine (4caa). Using a
mixture of petroleum etherꢀethyl acetate (200:1) as eluent. White solid: 64% yield (45
1
mg); mp 95ꢀ97 °C; IR (KBr, cmꢀ1): ν 2920, 1458, 1383, 1028, 953, 756; H NMR
(400 MHz, CDCl3, ppm): δ 8.69ꢀ8.66 (m, 2H), 8.27ꢀ8.24 (m, 2H), 7.72 (s, 1H), 7.57ꢀ
7.50 (m, 4H), 7.19 (t, J = 8.0 Hz, 4H ), 2.56 (s, 3H), 2.42 (s, 3H); 13C NMR (100 MHz,
CDCl3, ppm): δ 168.2, 164.1, 163.5, 163.1, 139.6, 137.4, 136.4, 135.7, 134.4 (d, J =
3.0 Hz), 132.1, 130.8, 130.6 (d, J = 8.0 Hz), 129.7, 129.0, 127.3, 126.9, 115.4 (d, J =
22.0 Hz), 114.2, 21.3, 20.7; MS (EI, 70 eV) m/z 354.38, 277.28, 232.26, 102.15,
77.12; HRMS (ESI) calcd C24H19FN2Na[M + Na]+ m/z 377.1424, found m/z 377.1422.
2-(4-Chlorophenyl)-4-(2,4-dimethylphenyl)-6-phenylpyrimidine(4daa). Using a
mixture of petroleum etherꢀethyl acetate (200:1) as eluent. White solid: 70% yield (52
1
mg); mp 123ꢀ125 °C; IR (KBr, cmꢀ1): ν 2920, 1571, 1522, 1359, 1088, 762; H NMR
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(400 MHz, CDCl3, ppm): δ 8.61 (d, J = 8.0 Hz, 2H), 8.26ꢀ8.23 (m, 2H), 7.73 (s, 1H),
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7.56ꢀ7.47 (m, 6H), 7.18 (d, J = 12.0 Hz, 2H), 2.55 (s, 3H), 2.42 (s, 3H); C NMR
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(100 MHz, CDCl3, ppm): δ 168.3, 164.2, 163.1, 139.6, 137.3, 136.8, 136.7, 136.4,
135.6, 132.2, 130.9, 129.8, 129.7, 129.0, 128.7, 127.3, 126.9, 114.5, 21.2, 20.7; MS
(EI, 70 eV) m/z 370.34, 293.26, 232.26, 185.21, 77.13; HRMS (ESI) calcd
C24H20ClN2 [M + H]+ m/z 371.1310, found m/z 371.1311.
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4-(2,4-Dimethylphenyl)-2-(4-methoxyphenyl)-6-phenylpyrimidine (4eaa). Using a
mixture of petroleum etherꢀethyl acetate (30:1) as eluent. Yellow oil : 68% yield (50
mg); IR (KBr, cmꢀ1): ν 2925, 1571, 1519, 1363, 1250, 1173, 1032, 770; 1H NMR (400
MHz, CDCl3, ppm): δ 8.65 (d, J = 8.0 Hz, 2H), 8.28ꢀ8.26 (m, 2H), 7.67 (s, 1H), 7.58ꢀ
7.52 (m, 4H), 7.19 (d, J = 12.0 Hz, 2H), 7.05 (d, J =12.0 Hz, 2H), 3.90 (s, 3H), 2.57 (s,
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3H), 2.43 (s, 3H); C NMR (100 MHz, CDCl3, ppm): δ 168.1, 164.0, 163.8, 161.8,
139.4, 137.7, 136.4, 136.0, 132.1, 131.0, 130.7, 130.1, 129.7, 128.9, 127.3, 126.9,
113.8, 113.6, 55.4, 21.3, 20.7; MS (EI, 70 eV) m/z 366.41, 289.32, 232.28, 183.31,
77.13; HRMS (ESI) calcd C25H23N2O [M +H]+ m/z 367.1805, found m/z 367.1805.
2-(4-Bromophenyl)-4-(2,4-dimethylphenyl)-6-phenylpyrimidine(4faa). Using a
mixture of petroleum etherꢀethyl acetate (200:1) as eluent. White solid: 43% yield (36
mg); mp 148ꢀ150 °C; IR (KBr, cmꢀ1): ν 3059, 2923, 1577, 1523, 1362, 1014, 769,
691; 1H NMR (400 MHz, CDCl3, ppm): δ 8.57ꢀ8.54 (m, 2H), 8.27ꢀ8.24 (m, 2H), 7.74
(s, 1H), 7.65 (d, J = 8.0 Hz, 2H), 7.58ꢀ7.55 (m, 3H), 7.52 (d, J = 4.0 Hz, 1H), 7.19 (d,
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J = 12.0 Hz, 2H), 2.56 (s, 3H), 2.43 (m, 3H); C NMR (100 MHz, CDCl3, ppm): δ
168.3, 164.2, 163.2, 139.6, 137.3, 137.2, 136.4, 135.7, 132.2, 131.6, 130.9, 130.1,
129.7, 129.0, 127.3, 127.0, 125.3, 114.5, 21.3, 20.8; MS (EI, 70 eV) m/z 415.29,
339.20, 232.26, 154.18, 77.13; HRMS (ESI) calcd C24H19BrN2Na [M + Na]+ m/z
437.0624, found m/z 437.0624.
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4-(2,4-Dimethylphenyl)-2-(3-methoxyphenyl)-6-phenylpyrimidine (4gaa). Using a
mixture of petroleum etherꢀethyl acetate (30:1) as eluent. Yellow oil: 60% yield (44
mg); IR (KBr, cmꢀ1): ν 2922, 1425, 1565, 1269, 756, 696; 1H NMR (400 MHz, CDCl3,
ppm): δ 8.29ꢀ8.24 (m, 4H), 7.74 (s, 1H), 7.56ꢀ7.54 (t, J = 10.0 Hz, 4H), 7.44 (t, J =
8.0 Hz, 1H), 7.18 (d, J = 12.0 Hz, 2H), 7.06 (d, J = 8.0 Hz, 1H), 3.93 (s, 3H), 2.57 (s,
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3H), 2.42 (s, 3H); C NMR (100 MHz, CDCl3, ppm): δ 168.1, 164.1, 163.8, 159.9,
139.7, 139.5, 137.5, 136.5, 135.8, 132.2, 130.8, 129.8, 129.5, 128.9, 127.3, 126.9,
121.1, 116.7, 114.4, 113.4, 55.4, 21.3, 20.8; MS (EI, 70 eV) m/z 366.46, 289.33,
232.28, 183.24, 77.13; HRMS (ESI) calcd C25H23N2O[M + H]+ m/z 367.1805, found
m/z 367.1807.
4-(2,4-Dimethylphenyl)-6-phenyl-2-(m-tolyl)pyrimidine (4haa). Using a mixture of
petroleum etherꢀethyl acetate (200:1) as eluent. Yellow oil: 59% yield (41 mg); IR
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(KBr, cmꢀ1): ν 3043, 2923, 1572, 1361, 766, 694; H NMR (400 MHz, CDCl3, ppm):
δ 8.49 (s, 2H), 8.28 (d, J = 4.0 Hz, 2H), 7.72 (s, 1H), 7.54 (d, J = 12.0 Hz, 4H), 7.42 (t,
J = 8.0 Hz, 1H), 7.33 (d, J = 8.0 Hz, 1H), 7.19 (d, J = 12.0 Hz, 2H), 2.57 (s, 3H), 2.50
(s, 3H), 2.43 (s, 3H); 13C NMR (100 MHz, CDCl3, ppm): δ 168.2, 164.2, 164.1, 139.5,
138.2, 138.0, 137.6, 136.4, 135.9, 132.1, 131.4, 130.7, 129.7, 129.1, 128.9, 128.4,
127.3, 126.9, 125.7, 114.3, 21.6, 21.3, 20.7; MS (EI, 70 eV) m/z 350.43, 273.30,
232.27, 154.19, 77.12; HRMS (ESI) calcd C25H22N2Na [M +Na]+ m/z 373.1675,
found m/z 373.1676.
2-(3-Bromophenyl)-4-(2,4-dimethylphenyl)-6-phenylpyrimidine (4iaa). Using a
mixture of petroleum etherꢀethyl acetate (200:1) as eluent. White solid: 39% yield (32
1
mg); mp 109ꢀ111 °C; IR (KBr, cmꢀ1): ν 3063, 2923, 1569, 1356, 764, 695; H NMR
(400 MHz, CDCl3, ppm): δ 8.82 (s, 1H), 8.61 (d, J = 8.0 Hz, 1H), 8.27ꢀ8.25 (m, 2H),
7.75 (s, 1H), 7.64ꢀ7.51 (m, 5H), 7.39 (t, J = 8.0 Hz, 1H), 7.19 (d, J = 12.0 Hz, 2H),
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2.56 (s, 3H), 2.43 (s, 3H); C NMR (100 MHz, CDCl3, ppm): δ 168.3, 164.2, 162.6,
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140.3, 139.7, 137.2, 136.4, 135.6, 133.4, 132.2, 131.5, 130.9, 130.0, 129.7, 129.0,
127.3, 127.1, 127.0, 122.8, 114.7, 21.3, 20.7; MS (EI, 70 eV) m/z 415.32, 337.23,
232.27, 154.19, 77.13; HRMS (ESI) calcd C24H20BrN2 [M + H]+ m/z 415.0804, found
m/z 415.0808.
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4-(2,4-Dimethylphenyl)-6-phenyl-2-(o-tolyl)pyrimidine (4jaa). Using a mixture of
petroleum etherꢀethyl acetate (200:1) as eluent. Yellow oil : 63% yield (44 mg); IR
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(KBr, cmꢀ1): ν 3049, 2924, 1572, 1520, 1358, 754, 692; H NMR (400 MHz, CDCl3,
ppm): δ 8.26ꢀ8.24 (m, 2H), 8.09ꢀ8.07 (m, 1H), 7.77 (s, 1H), 7.57ꢀ7.52 (m, 4H), 7.41ꢀ
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7.34 (m, 3H), 7.18 (d, J = 8.0 Hz, 2H), 2.76 (s, 3H), 2.56 (s, 3H), 2.43 (s, 3H); C
NMR (100 MHz, CDCl3, ppm): δ 168.0, 167.2, 163.7, 139.4, 138.7, 137.6, 137.4,
136.2, 135.9, 132.0, 131.4, 130.9, 130.8, 129.8, 129.3, 129.0, 127.3, 126.9, 125.9,
113.8, 21.8, 21.3, 20.8; MS (EI, 70 eV) m/z 350.40, 273.33, 232.28, 159.97, 77.11;
HRMS (ESI) calcd C25H23N2 [M + H]+ m/z 351.1856, found m/z 351.1862.
2-(2-Chlorophenyl)-4-(2,4-dimethylphenyl)-6-phenylpyrimidine (4kaa). Using a
mixture of petroleum etherꢀethyl acetate (200:1) as eluent. Yellow oil: 55% yield (41
mg); IR (KBr, cmꢀ1): ν 3059, 2924, 1574, 1520, 1361, 1034, 758; 1H NMR (400 MHz,
CDCl3, ppm): δ 8.25 (t, J = 2.0 Hz, 2H), 7.95 (t, J = 4.0 Hz, 1H), 7.80 (s, 1H), 7.56ꢀ
7.51(m, 5H), 7.40 (t, J = 4.0 Hz, 2H), 7.17 (d, J = 8.0 Hz, 2H), 2.56 (s, 3H), 2.41 (s,
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3H); C NMR (100 MHz, CDCl3, ppm): δ 168.3, 165.1, 164.1, 139.6, 138.3, 137.1,
136.3, 135.6, 133.1, 132.1, 132.0, 130.9, 130.6, 130.2, 129.9, 129.0, 127.5, 126.9,
126.7, 114.6, 21.3, 20.7; MS (EI, 70 eV) m/z 370.33, 293.26, 232.25, 154.20, 77.13;
HRMS (ESI) calcd C24H19ClN2Na [M + Na]+ m/z 393.1129, found m/z 393.1130.
4-(2,4-Dimethylphenyl)-2-methyl-6-phenylpyrimidine (4laa). Using a mixture of
petroleum etherꢀethyl acetate (30:1) as eluent. Yellow solid: 62% yield (34 mg); mp
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84ꢀ86 °C; IR (KBr, cmꢀ1): ν 2918, 1641, 1381, 1032, 758, 686; H NMR (400 MHz,
CDCl3, ppm): δ 8.11 ( t, J = 4.0 Hz, 2H), 7.60 (s, 1H), 7.51 (t, J = 4.0 Hz, 3H), 7.40 (d,
J = 8.0 Hz, 1H), 7.14 (d, J = 4.0 Hz, 2H), 2.87 (s, 3H), 2.44 (s, 3H), 2.39 (s, 3H); 13C
NMR (100 MHz, CDCl3, ppm): δ 168.0, 168.0, 164.1, 139.3, 137.4, 135.8, 135.8,
131.9, 130.7, 129.5, 129.0, 127.3, 126.9, 113.9, 26.5, 21.2, 20.3; MS (EI, 70 eV) m/z
274.33, 232.24, 197.22, 77.09; HRMS (ESI) calcd C19H19N2 [M + H]+ m/z 275.1543,
found m/z 275.1544.
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4-(2,4-Dimethylphenyl)-6-phenylpyrimidin-2-amine (4maa). Using a mixture of
petroleum etherꢀethyl acetate (10:1) as eluent. Yellow oil: 53% yield (29 mg); IR
(KBr, cmꢀ1): ν 3310, 3187, 1620, 1566, 1360, 764, 694; H NMR (400 MHz, CDCl3,
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ppm): δ 8.02ꢀ8.01 (m, 2H), 7.48 (t, J = 4.0 Hz, 3H), 7.36 (d, J = 8.0 Hz, 1H), 7.13ꢀ
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7.10 (m, 3H), 5.47 (s, 2H), 2.43 (s, 3H), 2.38 (s, 3H); C NMR (100 MHz, CDCl3,
ppm): δ 169.2, 165.5, 163.2, 139.0, 137.7, 136.0, 135.6, 131.8, 130.5, 129.0, 128.8,
127.2, 126.7, 108.0, 21.2, 20.3; MS (EI, 70 eV) m/z 275.33, 232.29, 198.25, 77.13;
HRMS (ESI) calcd C18H18N3 [M + H]+ m/z 276.1495, found m/z 276.1495.
4-(2,4-Dimethylphenyl)-N-methyl-6-phenylpyrimidin-2-amine (4naa). Using a
mixture of petroleum etherꢀethyl acetate (10:1) as eluent. Yellow solid: 61% yield (35
mg); mp 137ꢀ139 °C; IR (KBr, cmꢀ1): ν 3268, 2922, 1559, 1350, 759, 688; H NMR
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(400 MHz, CDCl3, ppm): δ 8.08 (t, J=4.0 Hz, 2H), 7.48 (t, J=4.0 Hz, 3H), 7.39 (d,
J=8.0 Hz, 1H), 7.10 (t, J=4.0 Hz, 3H), 5.46 (s, 1H), 3.10 (d, J=4.0 Hz, 3H), 2.46 (s,
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3H), 2.38 (s, 3H); C NMR (100 MHz, CDCl3, ppm): δ 168.9, 164.8, 163.1, 138.9,
138.0, 136.4, 135.9, 131.8, 130.3, 129.1, 128.7, 127.1, 126.7, 106.6, 28.4, 21.2, 20.4;
MS (EI, 70 eV) m/z 289.29, 212.25, 185.22, 77.11; HRMS (ESI) calcd C19H20N3 [M +
H]+ m/z 290.1652, found m/z 290.1659.
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2-Cyclopropyl-4-(2,4-dimethylphenyl)-6-phenylpyrimidine (4oaa). Using
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mixture of petroleum etherꢀethyl acetate (60:1) as eluent. Yellow oil: 70% yield (42
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mg); IR (KBr, cmꢀ1): ν 2924, 1574, 1450, 1367, 1034, 930, 768; HNMR (400
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MHz,CDCl3, ppm): δ 8.13ꢀ8.11 (m, 2H), 7.56 (s, 1H), 7.52ꢀ7.49 (m, 3H), 7.41 (d, J =
8.0 Hz, 1H), 7.13 (d, J = 8.0 Hz, 2H), 2.46 (s, 3H), 2.39 (s, 3H), 1.31ꢀ1.28 (m, 2H),
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1.12ꢀ1.08 (m, 2H); C NMR (100 MHz, CDCl3, ppm): δ 171.7, 167.7, 163.6, 139.2,
137.5, 136.2, 135.9, 132.0, 130.6, 129.5, 128.9, 127.2, 126.8, 113.4, 21.2, 20.6, 18.5,
10.6; MS (EI, 70 eV) m/z 300.34, 285.29, 223.26, 182.21, 77.09; HRMS (ESI) calcd
C21H21N2 [M + H]+ m/z 301.1699, found m/z 301.1705.
4-(2,4-Dimethylphenyl)-6-phenyl-2-(pyridin-4-yl)pyrimidine (4paa). Using a
mixture of petroleum etherꢀethyl acetate (10:1) as eluent. White solid: 56% yield (38
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mg); mp 137ꢀ139 °C; IR (KBr, cmꢀ1): ν 3042, 2922, 1730, 1587, 1368, 740, 679; H
NMR (400 MHz, CDCl3, ppm): δ 8.81 (d, J = 4.0 Hz, 2H), 8.49 (d, J = 8.0 Hz, 2H),
8.25 (t, J = 4.0 Hz, 2H), 7.80 (s, 1H), 7.56ꢀ7.50 (m, 4H), 7.18 (d, J = 12.0 Hz, 2H),
2.56 (s, 3H), 2.42 (s, 3H); 13C NMR (100 MHz, CDCl3, ppm): δ 168.5, 164.4, 162.0,
150.4, 145.5, 139.9, 136.9, 136.5, 135.2, 132.3, 131.1, 129.8, 129.1, 127.3, 127.0,
122.3, 115.6, 21.3, 20.8; MS (EI, 70 eV) m/z 337.16, 281.03, 260.06, 232.06, 77.03;
HRMS (ESI) calcd C23H20N3 [M + H]+ m/z 338.1652, found m/z 338.1660.
4-(2,4-Dimethylphenyl)-6-(4-pentylphenyl)-2-phenylpyrimidine (4aba). Using a
mixture of petroleum etherꢀethyl acetate (200:1) as eluent. Yellow oil: 64% yield (52
mg); IR (KBr, cmꢀ1): ν 2925, 1568, 1514, 1356, 753, 690; 1H NMR (400 MHz, CDCl3,
ppm): δ 8.73 (d, J = 8.0 Hz, 2H), 8.23 (d, J = 8.0 Hz, 2H), 7.73 (s, 1H), 7.55 (d, J =
8.0 Hz, 4H), 7.39 (d, J = 8.0 Hz, 2H), 7.21 (d, J =12.0 Hz, 2H), 2.74 (t, J = 4.0 Hz,
2H), 2.60 (s, 3H), 2.45 (s, 3H), 1.72 (t, J = 8.0 Hz, 2H), 1.40 (s, 4H), 0.96 (t, J = 4.0
Hz, 3H); 13C NMR (100 MHz, CDCl3, ppm): δ 168.1, 164.1, 164.0, 146.2, 139.4,
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138.4, 136.5, 136.0, 135.0, 132.1, 130.5, 129.7, 129.1, 128.5, 128.5, 127.2, 126.9,
114.0, 35.9, 31.5, 31.1, 22.6, 21.3, 20.8, 14.1; MS (EI, 70 eV) m/z 406.50, 348.36,
302.37, 259.30, 91.17, 77.13; HRMS (ESI) calcd C29H31N2 [M + H]+ m/z 407.2482,
found m/z 407.2483.
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4-(2,4-Dimethylphenyl)-2-phenyl-6-(p-tolyl)pyrimidine (4aca). Using a mixture of
petroleum etherꢀethyl acetate (200:1) as eluent. Yellow oil: 63% yield (44 mg); IR
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(KBr, cmꢀ1): ν 3031, 2923, 1572, 1517, 1362, 819, 760; H NMR (400 MHz, CDCl3,
ppm): δ 8.73 (d, J = 4.0 Hz, 2H), 8.21 (d, J =8.0 Hz, 2H), 7.72 (s, 1H), 7.56 (t, J = 8.0
Hz, 4H), 7.38 (d, J = 8.0 Hz, 2H), 7.21 (d, J = 12.0 Hz, 2H), 2.61 (d, J =8.0 Hz, 3H),
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2.48 (s, 3H), 2.45 (s, 3H); C NMR (100 MHz, CDCl3, ppm): δ 168.1, 164.0, 164.0,
141.1, 139.4, 138.4, 136.5, 136.0, 134.7, 132.1, 130.5, 129.8, 129.7, 128.5, 128.5,
127.2, 126.9, 114.0, 21.5, 21.3, 20.8; MS (EI, 70 eV) m/z 350.39, 259.28, 231.25,
77.15; HRMS (ESI) calcd C25H23N2 [M + H]+ m/z 351.1856, found m/z 351.1864.
4-(2,4-Dimethylphenyl)-6-(4-methoxyphenyl)-2-phenylpyrimidine (4ada). Using a
mixture of petroleum etherꢀethyl acetate (30:1) as eluent. Pale yellow oil: 67% yield
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(49 mg); IR (KBr, cmꢀ1): ν 3058, 2926, 1575, 1515, 1364, 826, 761; H NMR (400
MHz, CDCl3, ppm): δ 8.72 (d, J = 8.0 Hz, 2H), 8.28 (d, J = 8.0 Hz, 2H), 7.68 (s, 1H),
7.55 (m, J = 8.0 Hz, 4H), 7.20 (d, J =12.0 Hz, 2H), 7.08 (d, J =8.0 Hz, 2H), 3.90 (s,
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3H), 2.60 (s, 3H), 2.44 (s, 3H); C NMR (100 MHz, CDCl3, ppm): δ 167.9, 163.9,
163.6, 162.0, 139.4, 138.4, 136.4, 136.0, 132.1, 130.5, 129.9, 129.7, 128.8, 128.5,
128.5, 126.9, 114.3, 113.4, 55.5, 21.3, 20.8; MS (EI, 70 eV) m/z 366.35, 259.27,
232.27, 183.12, 77.14; HRMS (ESI) calcd C25H23N2O [M + H]+ m/z 367.1805, found
m/z 367.1813.
4-(4-Chlorophenyl)-6-(2,4-dimethylphenyl)-2-phenylpyrimidine (4aea). Using a
mixture of petroleum etherꢀethyl acetate (200:1) as eluent. White solid: 57% yield (42
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mg); mp 116ꢀ118 °C; IR (KBr, cmꢀ1): ν 2921, 1571, 1359, 756, 694; H NMR (400
MHz, CDCl3, ppm): δ 8.67ꢀ8.64 (m, 2H), 8.22 (d, J = 8.0 Hz, 2H), 7.69 (s, 1H), 7.53ꢀ
7.50 (m, 6H), 7.18 (t, J = 8.0 Hz, 2H), 2.57 (s, 3H), 2.42 (s, 3H); 13C NMR (100 MHz,
CDCl3, ppm): δ 168.4, 164.1, 162.9, 139.6, 138.1, 137.0, 136.5, 135.9, 135.7, 132.2,
130.7, 129.7, 129.2, 128.5, 128.5, 128.5, 126.9, 114.0, 21.3, 20.8; MS (EI, 70 eV) m/z
370.31, 259.27, 207.18, 154.21, 77.15; HRMS (ESI) calcd C24H20N2Cl [M +H]+ m/z
371.1310, found m/z 371.1308.
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4-(2,4-Dimethylphenyl)-6-(3-methoxyphenyl)-2-phenylpyrimidine (4afa). Using a
mixture of petroleum etherꢀethyl acetate (30:1) as eluent. Yellow oil: 61% yield (45
mg); IR (KBr, cmꢀ1): ν 2927, 1570, 1524, 1360, 1041, 763; H NMR (400 MHz,
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CDCl3, ppm): δ 8.68ꢀ8.66 (m, 2H), 7.88 (s, 1H), 7.81 (d, J = 8.0 Hz, 1H), 7.72 (s, 1H),
7.54ꢀ7.50 (m, 4H), 7.46 (t, J = 8.0 Hz, 1H), 7.18 (d, J = 8.0 Hz, 2H), 7.10ꢀ7.07 (m,
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1H), 3.95 (s, 3H), 2.57 (s, 3H), 2.42 (s, 3H); C NMR (100 MHz, CDCl3, ppm): δ
168.2, 164.0, 163.9, 160.2, 139.5, 139.0, 138.2, 136.4, 135.8, 132.1, 130.6, 129.9,
129.7, 128.5, 128.5, 126.9, 119.6, 116.4, 114.4, 112.7, 55.5, 21.3, 20.7; MS (EI, 70
eV) m/z 366.35, 259.28, 232.27, 154.20, 77.13; HRMS (ESI) calcd C25H23N2O [M
+H]+ m/z 367.1805, found m/z 367.1809.
4-(2,4-Dimethylphenyl)-2-phenyl-6-(4-(trifluoromethyl)phenyl)pyrimidine (4aga).
Using a mixture of petroleum etherꢀethyl acetate (200:1) as eluent. Yellow oil: 53%
yield (44 mg); IR (KBr, cmꢀ1): ν 2924, 1570, 1520, 1323, 1124, 819, 756; H NMR
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(400 MHz, CDCl3, ppm): δ 8.68ꢀ8.65 (m, 2H), 8.37 (d, J = 8.0 Hz, 2H), 7.82 (d, J =
8.0 Hz, 2H), 7.75 (s, 1H), 7.55ꢀ7.51 (m, 4H), 7.19 (t, J = 4.0 Hz, 2H), 2.58 (s, 3H),
2.43 (s, 3H); 13C NMR (100 MHz, CDCl3, ppm): δ 168.7, 164.2, 162.6, 140.9, 139.8,
137.9, 136.5, 135.5, 132.6, 132.2, 130.8, 129.7, 128.5, 128.5, 127.6, 127.0, 125.9 (q, J
= 4.0 Hz), 125.4, 114.6, 21.3, 20.8; MS (EI, 70 eV) m/z 404.37, 300.27, 259.26,
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232.24, 77.13; HRMS (ESI) calcd C25H20F3N2 [M + H]+ m/z 405.1573, found m/z
405.1579.
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4-(3-Chlorophenyl)-6-(2,4-dimethylphenyl)-2-phenylpyrimidine (4aha). Using a
mixture of petroleum etherꢀethyl acetate (200:1) as eluent. Black oil: 59% yield (44
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mg); IR (KBr, cmꢀ1): ν 2922, 1567, 1356, 760, 697; H NMR (400 MHz, CDCl3,
ppm): δ 8.67ꢀ8.65 (m, 2H), 8.28 (s, 1H), 8.12 (d, J = 8.0 Hz, 1H), 7.69 (s, 1H), 7.54ꢀ
7.46 (m, 6H), 7.19 (d, J = 12.0 Hz, 2H), 2.57 (s, 3H), 2.42 (s, 3H);13C NMR (100
MHz, CDCl3, ppm): δ 168.5, 164.1, 162.7, 139.7, 139.4, 138.0, 136.5, 135.6, 135.1,
132.2, 130.8, 130.7, 130.2, 129.7, 128.5, 127.4, 126.9, 125.3, 114.3, 21.3, 20.8; MS
(EI, 70 eV) m/z 370.31, 259.30, 231.24, 154.19, 77.13; HRMS (ESI) calcd
C24H20ClN2 [M + H]+ m/z 371.1310, found m/z 371.1311.
4-(2-Chlorophenyl)-6-(2,4-dimethylphenyl)-2-phenylpyrimidine (4aia). Using a
mixture of petroleum etherꢀethyl acetate (200:1) as eluent. Yellow oil: 43% yield (32
mg); IR (KBr, cmꢀ1): ν 3065, 2924, 1570, 1359, 1233, 700 ;1H NMR (400 MHz,
CDCl3, ppm): δ 8.68ꢀ8.66 (m, 2H), 8.29ꢀ8.28 (m, 1H), 8.14ꢀ8.11 (m, 1H), 7.69 (s, 1H),
7.56ꢀ7.48 (m, 7H), 7.19 (t, J = 8.0 Hz, 2H), 2.57 (s, 3H), 2.42 (s, 3H); 13C NMR (100
MHz, CDCl3, ppm): δ 168.5, 164.1, 162.7, 139.7, 139.4, 138.0, 136.5, 135.6, 135.1,
132.2, 130.9, 130.8, 130.7, 130.2, 129.7, 128.5, 127.4, 126.9, 125.3, 114.3, 21.3, 20.8;
MS (EI, 70 eV) m/z 370.31, 259.27, 232.28, 185.22, 154.20, 77.15; HRMS (ESI)
calcd C24H19ClN2Na [M + Na]+ m/z 393.1129, found m/z 393.1134.
4-(2,4-Dimethylphenyl)-6-(2-fluorophenyl)-2-phenylpyrimidine (4aja). Using a
mixture of petroleum etherꢀethyl acetate (200:1) as eluent. White solid: 49% yield (35
mg); mp 108ꢀ110 °C; IR (KBr, cmꢀ1): ν 2924, 1571, 1364, 1217, 760, 695; H NMR
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(400 MHz, CDCl3, ppm): δ 8.67ꢀ8.64 (m, 2H), 8.45ꢀ8.40 (m, 1H), 7.88 (s, 1H), 7.56ꢀ
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7.47 (m, 5H), 7.39ꢀ7.35 (m, 1H), 7.24ꢀ7.17 (m, 3H), 2.58 (s, 3H), 2.42 (s, 3H); C
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NMR (100 MHz, CDCl3, ppm): δ 167.9, 164.0, 160.2, 139.5, 138.2, 136.5, 135.7,
132.1, 132.0 (d, J = 9.0 Hz), 131.1 (d, J = 3.0Hz), 130.6, 129.9, 128.5, 128.4, 126.9,
124.7 (d, J = 4.0 Hz), 118.6, 118.5, 116.5 (d, J = 23.0 Hz), 100.0, 21.3, 20.8; MS (EI,
70 eV) m/z 354.32, 259.28, 232.25, 154.20, 77.14; HRMS (ESI) calcd C24H19FN2Na
[M + Na]+ m/z 377.1424, found m/z 377.1427.
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4-(2,4-Dimethylphenyl)-6-(2-methoxyphenyl)-2-phenylpyrimidine (4aka). Using a
mixture of petroleum etherꢀethyl acetate (30:1) as eluent. Pale yellow solid: 57%
yield (42 mg); mp 130ꢀ132 °C; IR (KBr, cmꢀ1): ν 2929, 1568, 1362, 1246, 755, 697;
1H NMR (400 MHz, CDCl3, ppm): δ 8.75 (t, J = 4.0 Hz, 2H), 8.38ꢀ8.36 (m, 1H), 8.09
(s, 1H), 7.65ꢀ7.50 (m, 5H), 7.28ꢀ7.23 (m, 3H), 7.09 (d, J = 8.0 Hz, 1H), 3.96 (s, 3H),
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2.67 (s, 3H), 2.48 (s, 3H); C NMR (100 MHz, CDCl3, ppm): δ 166.8, 163.8, 162.6,
158.2, 139.3, 138.6, 136.5, 136.3, 132.1, 131.6, 131.5, 130.4, 130.0, 128.5, 128.4,
127.0, 126.9, 121.2, 119.5, 111.6, 55.7, 21.3, 20.8; MS (EI, 70 eV) m/z 366.38,
259.27, 154.20, 77.12; HRMS (ESI) calcd C25H23N2O [M + H]+ m/z 367.1805, found
m/z 367.1811.
4-(2,4-dimethylphenyl)-2-phenyl-6-(pyridin-2-yl)pyrimidine (4ala). Using
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mixture of petroleum etherꢀethyl acetate (10:1) as eluent. Green solid: 58% yield (39
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mg); mp 118ꢀ120 °C; IR (KBr, cmꢀ1): ν 3057, 2923, 1526, 1361, 743, 696; H NMR
(400 MHz, CDCl3, ppm): δ 8.79ꢀ8.73 (m, 4H), 8.49 (s, 1H), 7.92ꢀ7.88 (m, 1H), 7.64
(d, J = 8.0 Hz, 1H), 7.60ꢀ7.53 (m, 3H), 7.41ꢀ7.39 (m, 1H), 7.19 (d, J = 8.0 Hz, 2H),
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2.64 (s, 3H), 2.43 (s, 3H); C NMR (100 MHz, CDCl3, ppm): δ 168.8, 163.7, 163.0,
154.8, 149.5, 139.5, 138.2, 137.1, 136.6, 135.7, 132.2, 130.6, 130.0, 128.5, 128.5,
126.9, 125.2, 121.9, 114.7, 21.3, 21.0; MS (EI, 70 eV) m/z 337.18, 259.13, 233.16,
78.10; HRMS (ESI) calcd C23H19N3Na [M + Na]+ m/z 360.1471, found m/z 360.1478.
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4-(2,4-dimethylphenyl)-2-phenyl-6-(thiophen-3-yl)pyrimidine (4ama). Using a
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mixture of petroleum etherꢀethyl acetate (100:1) as eluent. Brown oil: 51% yield (35
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mg); IR (KBr, cmꢀ1): ν 2920, 1742, 1569, 1372, 1242, 755, 689; H NMR (400 MHz,
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CDCl3, ppm): δ 8.71 (d, J = 4.0 Hz, 2H), 8.29 (d, J = 4.0 Hz, 1H), 7.88 (d, J = 4.0 Hz,
1H), 7.58ꢀ7.53 (m, 5H), 7.48 (t, J = 4.0 Hz, 1H), 7.19 (d, J = 12.0 Hz, 2H), 2.62 (d, J
= 16.0 Hz, 3H), 2.45 (s, 3H); 13C NMR (100 MHz, CDCl3, ppm): δ 168.3, 164.1,
159.9, 140.9, 139.5, 138.3, 136.5, 135.8, 132.2, 130.6, 129.7, 128.5, 128.5, 126.9,
126.8, 126.6, 126.2, 114.1, 21.3, 20.8; MS (EI, 70 eV) m/z 342.15, 259.10, 223.08,
154.10, 77.06; HRMS (ESI) calcd C22H19N2S [M + H]+ m/z 343.1263, found m/z
343.1273.
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4-(4-Methoxyphenyl)-2,6-diphenylpyrimidine (4aab). Using
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petroleum etherꢀethyl acetate (30:1) as eluent. White solid: 65% yield (44 mg); mp
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144ꢀ146 °C; IR (KBr, cmꢀ1): ν 3061, 2924, 1571, 1520, 1363, 1247, 754, 691; H
NMR (400 MHz, CDCl3, ppm): δ 8.76ꢀ8.73 (m, 2H), 8.30ꢀ8.26 (m, 4H), 7.93 (s, 1H),
7.58ꢀ7.54 (m, 6H), 7.07 (d, J = 12.0 Hz, 2H), 3.89 (s, 3H); 13C NMR (100 MHz,
CDCl3, ppm): δ 164.5, 164.4, 164.2, 162.0, 138.4, 137.7, 130.7, 130.5, 130.0, 128.9,
128.8, 128.5, 128.4, 127.3, 114.3, 109.4, 55.4; MS (EI, 70 eV) m/z 338.29, 235.23,
220.21, 132.14, 77.13; HRMS (ESI) calcd C23H19N2O [M + H]+ m/z 339.1492, found
m/z 339.1494.
2,4-Diphenyl-6-(p-tolyl)pyrimidine (4aac). Using a mixture of petroleum etherꢀethyl
acetate (200:1) as eluent. Pale silver solid: 62% yield (40 mg); mp 143ꢀ145 °C; IR
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(KBr, cmꢀ1): ν 3045, 2922, 1576, 1521, 1362, 750, 688; H NMR (400 MHz, CDCl3,
ppm): δ 8.76 (t, J = 4.0 Hz, 2H), 8.30 (t, J = 4.0 Hz, 2H), 8.21 (d, J = 8.0 Hz, 2H),
7.98 (s, 1H), 7.59ꢀ7.54 (m, 6H), 7.37 (d, J = 8.0 Hz, 2H), 2.47 (s, 3H); 13C NMR (100
MHz, CDCl3, ppm): δ 164.7, 164.6, 164.5, 141.1, 138.3, 137.7, 134.8, 130.7, 130.6,
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129.7, 128.9, 128.5, 128.4, 127.3, 127.2, 109.9, 21.5; MS (EI, 70 eV) m/z 322.36,
219.27, 102.18, 77.18; HRMS (ESI) calcd C23H19N2 [M +H]+ m/z 323.1543, found
m/z 323.1549.
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4-(4-Chlorophenyl)-2,6-diphenylpyrimidine (4aad). Using a mixture of petroleum
etherꢀethyl acetate (200:1) as eluent. White solid: 57% yield (39 mg); mp 161ꢀ163 °C;
IR (KBr, cmꢀ1): ν 3056, 2922, 1577, 1523, 1361, 752, 688 ;1H NMR (400 MHz,
CDCl3, ppm): δ 8.72ꢀ8.70 (m, 2H), 8.29ꢀ8.23 (m, 4H), 7.96 (s, 1H), 7.57ꢀ7.52 (m,
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8H); C NMR (100 MHz, CDCl3, ppm): δ 165.0, 164.6, 163.5, 138.0, 137.4, 137.0,
136.0, 130.9, 130.8, 129.2, 129.0, 128.6, 128.5, 127.3, 110.0; MS (EI, 70 eV) m/z
342.29, 239.18, 204.21, 102.15; HRMS (ESI) calcd C22H16ClN2 [M + H]+ m/z
343.0997, found m/z 343.0998.
4-(4-(tert-Butyl)phenyl)-2,6-diphenylpyrimidine (4aae). Using a mixture of
petroleum etherꢀethyl acetate (200:1) as eluent. Pale yellow solid: 62% yield (45 mg);
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mp 118ꢀ120 °C; IR (KBr, cmꢀ1): ν 3058, 2959, 1574, 1521, 1366, 751, 692; H NMR
(400 MHz, CDCl3, ppm): δ 8.77 (d, J = 8.0 Hz, 2H), 8.32ꢀ8.24 (m, 4H), 8.01 (s, 1H),
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7.62ꢀ6.56 (m, 8H), 1.42 (d, J = 8.0 Hz, 9H); C NMR (100 MHz, CDCl3, ppm): δ
164.8, 164.6, 164.5, 154.3, 138.3, 137.7, 134.8, 130.7, 130.6, 128.9, 128.5, 128.5,
127.3, 127.1, 125.9, 110.1, 34.9, 31.3; MS (EI, 70 eV) m/z 364.40, 349.38, 174.78,
104.16, 77.12; HRMS (ESI) calcd C26H25N2[M + H]+ m/z 365.2012, found m/z
365.2019.
4-(3-Fluorophenyl)-2,6-diphenylpyrimidine (4aaf). Using a mixture of petroleum
etherꢀethyl acetate (200:1) as eluent. White solid: 54% yield (35 mg); mp 193ꢀ195 °C;
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IR (KBr, cmꢀ1): ν 3060, 2920, 1574, 1529, 1357, 747, 682; H NMR (400 MHz,
CDCl3, ppm): δ 8.78ꢀ8.72 (m, 2H), 8.32ꢀ8.30 (m, 2H), 8.08ꢀ8.03 (m, 2H), 7.98 (s, 1H),
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7.60ꢀ7.52 (m, 7H), 7.29ꢀ7.24 (m, 1H); C NMR (100 MHz, CDCl3, ppm): δ 165.0,
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164.6, 164.3 (d, J = 2.0 Hz), 162.1, 139.9 (d, J = 7.0 Hz), 137.9, 137.3, 130.9 (d, J =
14.0 Hz), 130.4 (d, J = 8.0 Hz), 129.0, 128.9, 128.5, 128.5, 127.3, 122.8 (d, J = 3.0
Hz), 117.6 (d, J = 21.0 Hz), 114.3 (d, J = 21.0 Hz), 110.2; MS (EI, 70 eV) m/z 326.26,
223.27, 120.12, 102.13, 77.12; HRMS (ESI) calcd C22H16FN2 [M + H]+ m/z 327.1292,
found m/z 327.1296.
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2,4,6-Triphenylpyrimidine (4aag). Using a mixture of petroleum etherꢀethyl acetate
(200:1) as eluent. White solid: 68% yield (42 mg); mp 183ꢀ185 °C; IR (KBr, cmꢀ1): ν
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3053, 2920, 1572, 1525, 1359, 737, 681; H NMR (400 MHz, CDCl3, ppm): δ 8.79ꢀ
8.78 (m, 2H), 8.33ꢀ8.30 (m, 4H), 8.01 (s, 1H), 7.61ꢀ7.54 (m, 9H); 13C NMR (100
MHz, CDCl3, ppm): δ 164.8, 164.5, 138.3, 137.6, 130.8, 130.7, 128.9, 128.6, 128.5,
127.3, 110.3; MS (EI, 70 eV) m/z 308.34, 205.26, 154.30, 102.13, 76.16; HRMS
(ESI) calcd C22H17N2 [M + H]+ m/z 309.1386, found m/z 309.1389.
4-(2-Chlorophenyl)-2,6-diphenylpyrimidine (4aah). Using a mixture of petroleum
etherꢀethyl acetate (200:1) as eluent. White solid: 53% yield (36 mg); mp 124ꢀ126 °C;
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IR (KBr, cmꢀ1): ν 3061, 2924, 1572, 1364, 752, 693; H NMR (400 MHz, CDCl3,
ppm): δ 8.74ꢀ8.71 (m, 2H), 8.32ꢀ8.30 (m, 2H), 8.04 (s, 1H), 7.89ꢀ7.87 (m, 2H), 7.60ꢀ
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7.54 (m, 7H), 7.49ꢀ7.41 (m, 2H); C NMR (100 MHz, CDCl3, ppm): δ 164.7, 164.7,
163.9, 138.0, 137.6, 137.3, 132.5, 131.8, 130.9, 130.8, 130.7, 130.5, 129.0, 128.5,
128.5, 127.4, 127.3, 115.2; MS (EI, 70 eV) m/z 342.25, 239.23, 204.26, 136.16,
76.18; HRMS (ESI) calcd C22H15ClN2Na [M + Na]+ m/z 365.0816, found m/z
365.0823.
4-(2-Methoxyphenyl)-2,6-diphenylpyrimidine (4aai). Using a mixture of petroleum
etherꢀethyl acetate (30:1) as eluent. White solid: 59% yield (40 mg); mp 74ꢀ76 °C; IR
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(KBr, cmꢀ1): ν 3061, 2940, 1572, 1365, 1247, 749, 692; H NMR (400 MHz, CDCl3,
ppm): δ 8.76ꢀ8.74 (m, 2H), 8.33ꢀ8.28 (m, 4H), 7.60ꢀ7.47 (m, 7H), 7.22ꢀ7.18 (m, 1H),
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7.08 (d, J = 8.0 MHz, 1H), 3.96 (s, 3H); 13C NMR (100 MHz, CDCl3, ppm): δ 164.3,
163.7, 163.5, 158.2, 138.5, 138.0, 131.6, 131.4, 130.5, 130.4, 128.9, 128.4, 128.4,
127.4, 127.0, 121.2, 115.5, 111.7, 55.8; MS (EI, 70 eV) m/z 338.31, 233.26, 206.23,
102.15, 77.16; HRMS (ESI) calcd C23H18N2NaO [M + Na]+ m/z 361.1311, found m/z
361.1316.
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2,4-Diphenyl-6-(pyridin-4-yl)pyrimidine (4aaj). Using a mixture of petroleum
etherꢀethyl acetate (10:1) as eluent. Pale yellow solid: 41% yield (25 mg); mp 205ꢀ
207 °C; IR (KBr, cmꢀ1): ν 3033, 2917, 1568, 1516, 1358, 742, 684 ;1H NMR (400
MHz, CDCl3, ppm): δ 8.85 (d, J = 4.0 Hz, 2H), 8.72ꢀ8.70 (m, 2H), 8.30ꢀ8.28 (m, 2H),
8.14 (d, J = 8.0 Hz, 2H), 8.03 (s, 1H), 7.58ꢀ7.54 (m, 6H); 13C NMR (100 MHz, CDCl3,
ppm): δ 165.5, 165.0, 162.3, 150.6, 144.9, 137.6, 137.0, 131.2, 131.0, 129.0, 128.6,
128.5, 127.3, 121.2, 110.6; MS (EI, 70 eV) m/z 309.31, 206.25, 154.80, 103.13,
77.14; HRMS (ESI) calcd C21H16N3 [M + H]+ m/z 310.1339, found m/z 310.1343.
4-(Furan-2-yl)-2,6-diphenylpyrimidine (4aak). Using a mixture of petroleum etherꢀ
ethyl acetate (50:1) as eluent. Gold solid: 62% yield (37 mg); mp 158ꢀ160 °C; IR
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(KBr, cmꢀ1): ν 3055, 2923, 1551, 1359, 743, 689; H NMR (400 MHz, CDCl3, ppm):
δ 8.69ꢀ8.67 (m, 2H), 8.31ꢀ8.29 (m, 2H), 7.95 (s, 1H), 7.65 (s, 1H), 7.59ꢀ7.52 (m, 6H),
7.47 (d, J = 4.0 Hz, 1H), 6.64ꢀ6.63 (m, 1H);13C NMR (100 MHz, CDCl3, ppm): δ
164.6, 164.5, 156.4, 152.7, 144.8, 138.0, 137.4, 130.9, 130.7, 128.9, 128.9, 128.4,
127.3, 112.5, 112.1, 108.0; MS (EI, 70 eV) m/z 298.30, 195.23, 92.14, 77.15; HRMS
(ESI) calcd C20H15N2O [M + H]+ m/z 299.1179, found m/z 299.1179.
2,4-diphenyl-6-(thiophen-3-yl)pyrimidine (4aal). Using a mixture of petroleum
etherꢀethyl acetate (100:1) as eluent. Brown solid: 53% yield (33 mg); mp 166ꢀ
168 °C; IR (KBr, cmꢀ1): ν 2919, 1637, 1267, 746; 1H NMR (400 MHz, CDCl3, ppm):
δ 8.71 (d, J = 8.0 Hz, 2H), 8.28 (t, J = 4.0 Hz, 3H ), 7.89ꢀ7.84 (m, 2H), 7.55ꢀ7.48 (m,
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7H); C NMR (100 MHz, CDCl3, ppm): δ 164.7, 164.6, 160.5, 140.9, 138.1, 137.5,
130.8, 130.7, 128.9, 128.5, 128.5, 127.3, 126.7, 126.7, 126.2, 110.1; MS (EI, 70 eV)
m/z 314.08, 210.07, 184.05, 108.03, 76.08; HRMS (ESI) calcd C20H15N2S [M + H]+
m/z 315.0950, found m/z 315.0951.
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4-(1-methyl-1H-pyrrol-2-yl)-2,6-diphenylpyrimidine (4aam). Using a mixture of
petroleum etherꢀethyl acetate (50:1) as eluent. Black solid: 74% yield (46 mg); mp
120ꢀ122 °C; IR (KBr, cmꢀ1): ν 2922, 1570, 1526, 1479, 1365, 730, 693; 1H NMR (400
MHz, CDCl3, ppm): δ 8.69ꢀ8.66 (m, 2H), 8.30ꢀ8.28 (m, 2H), 7.82 (s, 1H), 7.61ꢀ7.56
(m, 6H), 7.02ꢀ7.00 (m, 1H), 6.89ꢀ6.88 (m, 1H), 6.32ꢀ6.31 (m, 1H), 4.27 (d, J = 8.0 Hz,
13
3H); C NMR (100 MHz, CDCl3, ppm): δ 163.8, 163.5, 159.5, 138.6, 137.8, 130.6,
130.5, 130.2, 128.9, 128.9, 128.5, 128.4, 127.2, 113.8, 110.2, 108.5, 38.4; MS (EI, 70
eV) m/z 311.25, 207.17, 104.12, 77.09; HRMS (ESI) calcd C21H18N3 [M + H]+ m/z
312.1495, found m/z 312.1499.
4-(naphthalen-1-yl)-2,6-diphenylpyrimidine (4aan). Using a mixture of petroleum
etherꢀethyl acetate (100:1) as eluent. Brown solid: 47% yield (34 mg); mp 128ꢀ
1
130 °C; IR (KBr, cmꢀ1): ν 3745, 2921, 1565, 1523, 1364, 751, 694; H NMR (400
MHz, CDCl3, ppm): δ 8.75ꢀ8.73 (m, 2H), 8.39 (t, J = 4.0 Hz, 1H), 8.34ꢀ8.32 (m, 2H),
8.02 (d, J = 8.0 Hz, 1H), 7.98 (t, J = 4.0 Hz, 1H), 7.92 (s, 1H), 7.82 (d, J = 4.0 Hz,
13
1H ), 7.66ꢀ7.54 (m, 9H); C NMR (100 MHz, CDCl3, ppm): δ 167.5, 164.5, 164.4,
138.1, 137.3, 136.9, 134.1, 130.9, 130.9, 130.8, 130.2, 129.0, 128.6, 128.6, 128.6,
127.9, 127.4, 127.0, 126.2, 125.5, 125.4, 115.4; MS (EI, 70 eV) m/z 358.00, 254.13,
152.09, 104.10, 77.06; HRMS (ESI) calcd C26H19N2 [M + H]+ m/z 359.1543, found
m/z 359.1547.
2-(3-bromophenyl)-4,6-diphenylpyrimidine (4iag). Using a mixture of petroleum
etherꢀethyl acetate (200:1) as eluent. Yellow soild: 47% yield; mp 142ꢀ144 °C; IR
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(KBr, cmꢀ1): ν 2922, 1764, 1513, 1255, 1041, 754; 1H NMR (400 MHz, CDCl3, ppm):
δ 8.85 (s, 1H), 8.65 (d, J = 8.0 Hz, 1H), 8.27ꢀ8.24 (m, 4H), 7.98 (s, 1H), 7.64 (d, J =
8.0 Hz, 1H), 7.59ꢀ7.53 (m, 6H), 7.40 (t, J = 8.0 Hz, 1H); 13C NMR (100 MHz, CDCl3,
ppm): δ 164.8, 163.1, 140.3, 137.2, 133.5, 131.5, 131.0, 130.0, 129.0, 127.3, 127.1,
122.8, 110.7; MS (EI, 70 eV) m/z 386.00, 204.14, 128.23, 102.09, 77.09; HRMS
(ESI) calcd C22H16BrN2 [M + H]+ m/z 387.0491, found m/z 387.0495.
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2-(3'-chloro-[1,1'-biphenyl]-3-yl)-4,6-diphenylpyrimidine (6). Using a mixture of
petroleum etherꢀethyl acetate (100:1) as eluent. White soild: 86% yield; mp 134ꢀ
1
136 °C; IR (KBr, cmꢀ1): ν 2922, 1571, 1526, 1264, 756, 693; H NMR (400 MHz,
CDCl3, ppm): δ 8.91 (t, J = 2.0 Hz, 1H), 8.76ꢀ8.74 (m, 1H), 8.30ꢀ8.28 (m, 4H), 7.97 (s,
1H), 7.75 (s, 1H), 7.71ꢀ7.68 (m, 1H), 7.64ꢀ7.57 (m, 8H), 7.46ꢀ7.39 (m, 2H); 13C NMR
(100 MHz, CDCl3, ppm): δ 164.8, 164.2, 143.2, 140.0, 138.9, 137.5, 134.7, 130.9,
130.1, 129.4, 129.1, 129.0, 128.2, 127.5, 127.4, 127.4, 127.1, 125.6, 110.5; HRMS
(ESI) calcd C28H20ClN2 [M + H]+ m/z 419.1310, found m/z 419.1315.
1,3-diphenylprop-2-yn-1-ol (7). Using a mixture of petroleum etherꢀethyl acetate
(5:1) as eluent. Brown oil; IR (KBr, cmꢀ1): ν 3424, 2924, 1596, 1268, 1180, 754, 692;
1H NMR (400 MHz, CDCl3, ppm): δ 7.71ꢀ7.68 (m, 2H), 7.58ꢀ7.55 (m, 2H), 7.48ꢀ7.35
(m, 6H), 5.75 (s, 1H), 3.43 (s, 1H); 13C NMR (100 MHz, CDCl3, ppm): δ 140.9, 131.9,
128.8, 128.7, 128.5, 128.5, 127.0, 122.7, 89.2, 86.7, 65.1; MS (EI, 70 eV) m/z
208.00, 179.11, 152.07, 77.07; HRMS (ESI) calcd C15H12NaO [M+Na]+ m/z 231.0780,
found m/z 231.0776.
ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the ACS Publications
website at DOI: 10.1021/acs.joc.
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1H and 13C spectra of all synthesized compounds (PDF)
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AUTHOR INFORMATION
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Corresponding Author
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* Eꢀmail: jianghf@scut.edu.cn. Fax: (+86) 20ꢀ8711ꢀ2906.
* Eꢀmail: cewuwq@scut.edu.cn
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
We are grateful to the National Program on Key Research Project (2016YFA0602900),
the National Natural Science Foundation of China (21420102003, 21662002,
21602031), Pearl River S&T Nova Program of Guangzhou (201610010160), the
Advanced Innovation Research Teams Project of Jiangxi Province (20133BCB24011),
and Jiangxi Natural Science Foundation (20151BAB203011 and 20171BAB203010).
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