Transition Metal Free Intermolecular Direct Oxidative C-N Bond Formation to Polysubstituted Pyrimidines Using Molecular Oxygen as the Sole Oxidant

Article abstract of DOI:10.1021/acs.joc.6b00867

Various polysubstituted pyrimidines are smoothly formed via a base-promoted intermolecular oxidation C-N bond formation of allylic C(sp³)-H and vinylic C(sp²)-H of allyllic compounds with amidines using O₂ as the sole oxid

Full text of DOI:10.1021/acs.joc.6b00867

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Article
Transition-Metal-Free Intermolecular Direct Oxidative C-N Bond Formation
to Polysubstituted Pyrimidines Using Molecular Oxygen as Sole Oxidant
Wei Guo, Chunsheng Li, Jianhua Liao, Fanghua Ji, Dongqing Liu, Wanqing Wu, and Huanfeng Jiang
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b00867 • Publication Date (Web): 08 Jun 2016
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Transition-Metal-Free Intermolecular Direct Oxidative C-N
Bond Formation to Polysubstituted Pyrimidines Using
Molecular Oxygen as Sole Oxidant
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Wei Guo,†,‡ Chunsheng Li,† Jianhua Liao,† Fanghua Ji,† Dongqing Liu, † Wanqing
Wu,*, † Huanfeng Jiang,*, †
†Key Laboratory of Functional Molecular Engineering of Guangdong Province, School of
Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510640,
China
‡Key Laboratory of Organoꢀpharmaceutical Chemistry of Jiangxi Province, Gannan Normal
University, Ganzhou 341000, China
Fax: (+86) 20ꢀ8711ꢀ2906; Eꢀmail: cewuwq@scut.edu.cn, jianghf@scut.edu.cn
ABSTRACT: Various polysubstituted pyrimidines are smoothly formed via
baseꢀpromoted intermolecular oxidation CꢀN bond formation of allylic C(sp3)ꢀH and
vinylic C(sp2)ꢀH of allyllic compounds with amidines using O2 as the sole oxidant
a
.
This protocol features protectingꢀgroup free nitrogen sources, good functional group
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tolerance, high atom economy and environmental advantages.
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INTRODUCTION
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Pyrimidines represent important building blocks in natural products, agrochemicals,
pharmaceuticals, and functional materials.1 They are also possess large range of
application as antiꢀinflammatory, antimicrobial, antimalarial agents, cytotoxic
inhibitors and photophysical materials.2 Numbers of synthetic routes have also been
developed for the synthesis of pyrimidines through the cascade condensation
cyclizationꢀoxidation of amidines with 1,3ꢀdicarbonyl derivatives, α,βꢀunsaturated
ketones, propargylic alcohols, propargylamines, and reaction of α,αꢀdibromo oxime
ethers with Grignard reagents.3 Movassaghi et al. reported a singleꢀstep procedure for
the synthesis of primidines from Nꢀvinyl amides and nitrles using 2ꢀchloropyridine
with trifluoromethanesulfonic anhydride as amide activation reagents (Scheme 1, a).4
Campagne et al. found the transformation of Cbzꢀprotected βꢀenaminones with
amides into 2,4,6ꢀtrisubstituted pyrimidines (Scheme 1, b).5 Recently, Kempe et al.
developed a iridiumꢀcatalyzed multicomponent synthesis of pyrimidines from
amidines and up to three (different) alcohols (Scheme 1, c).6 Konakahara et al. also
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successfully synthesized 4,5ꢀdisubstituted pyrimidine derivatives via
a
ZnCl2ꢀcatalyzed threeꢀcomponent coupling reaction of enamines, triethyl
orthoformate, and ammonium acetate.7 However, most of the above mentioned
methods suffered from one or more drawbacks such as harsh reaction conditions
(special reaction medium and reagents, microwave irradiation, transitionꢀmetals) and
starting materials that require multistep synthesis. Therefore, the development of
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simple and efficient procedures for acquisition of pyrimidines from easily available
starting materials under mild conditions continues to attract the interest of organic
chemists due to their remarkable application value.
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Direct CꢀH amination has emerged as powerful synthetic protocol for the CꢀN
bondꢀforming reactions and the construction of Nꢀheterocycles, avoiding the
preꢀinstallation of transformable functional groups and possessing atom economy and
environmental sustainability.8 Many attractive approaches have been dominated in the
presence of transition metal catalysts, Pd,9 Rh,10 Cu,11 Ni,12 Au,13 involving intraꢀ or
interꢀ molecular amination processes. Meanwhile, most of the preꢀactivated or
preꢀoxidized amination substrates bearing strong electronꢀwithdrawing groups, such
as Nꢀcarboxylates,10,14 Nꢀtosylates,13,15 Nꢀnosyloxyꢀcarbamates,16 Nꢀhalides,17
Nꢀfluorobenzenesulfonimides,18
diꢀtertꢀbutyldiaziridinones,19
azides20
and
diaziridine21 are universal for these transformations. Despite of all progress in
transitionꢀmetalꢀcatalyzed CꢀH amination, the moisture sensitivity, environmental
toxicity, costꢀeffectiveness as well as the residual transition metal impurities in the
final products remains a major problem, affecting the practical applicability,
especially in the preparation of pharmaceutical agents and functional materials.22 In
this particular aspect, the alternative transitionꢀmetal free direct CꢀH amination is a
worthwhile assignment. In some pioneering examples, the intermolecular aminations
were mediated/catalyzed/promoted by hypervalent iodine (III) reagents,23 bromide,24
NIS,25 H2O2,26 DTBP27 and TBHP.28 However, the use of overstoichiometric amounts
of oxidants also has high expense and would produce a large amount of byproducts.
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Scheme 1. Synthesis of Polysubstituted Pyrimidines
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For green and sustainable chemistry, molecular oxygen (O2) is considered to be an
ideal oxidant due to its natural, inexpensive, and environmentally friendly
characteristics, and therefore shows attractive academic and industrial prospects.29 In
the past few years, our group has developed a series of CꢀH activation reactions using
O2 as the terminal oxidant,30 and we envision that the employment of O2 could be
applied to the allylic CꢀH amination. Herein, we disclose a baseꢀpromoted
intermolecular oxidation CꢀN bond formation of allylic C(sp3)ꢀH and vinylic C(sp2)ꢀH
of allyllic compounds with amidines to afford polysubstituted pyrimidines using O2 as
the sole oxidant, in which amidines were used as naked nitrogen sources without any
protecting groups (Scheme 1, d).
RESULTS AND DISCUSSION
Table 1. Selected Optimization Studiesa
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Entry
1
Base
K2CO3
K3PO4
Oxidantb
O2
T (oC)
120
120
120
120
100
80
Yield (%)c
28
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2
O2
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3
KOH
O2
80
4
Cs2CO3
Cs2CO3
Cs2CO3
(CH3)3COK
CH3ONa
DBU
O2
85
5
O2
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O2
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O2
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O2
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O2
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14d
15 d
16 d
17 d
18d
19 d
20d
21e
22f
23g
DABCO
Et3N
O2
trace
12
O2
Pyridine
/
O2
n.d.
n.d.
n.d.
16
O2
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
/
TBHP
DTHP
35% H2O2
K2S2O8
pꢀBQ
DDQ
O2
n.d.
18
trace
trace
trace
41
O2
trace
trace
O2
aReaction conditions: Unless otherwise noted, all reactions were performed with 1a
(0.25 mmol), 2a (0.30 mmol), oxidant (0.25 mmol) and base (2 equiv) in 1.0 mL
DMSO for 24 h. bO2 was performed at 1 atm. cGC yield based on 1a with nꢀdodecane
as an internal standard. At vacuum condition. DMF as the solvent. Toluene as the
solvent. g1,4ꢀDioxane as the solvent.
d
e
f
We initially chose easily accessible benzamidine (1a) with allylbenzene (2a) as
the model substrates to test the feasibility of our process (Table 1). Fortunately, the
desired product (3aa) was obtained in DMSO in the presence of base and oxygen
atmosphere. Some conclusions could be drawn from the results: (i) Inorganic bases
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such as K3PO4, KOH and Cs2CO3 facilitated the transformation, with the strong bases
being the best choice (Table 1, entries 1ꢀ4). (ii) Other organic bases screened inhibited
this reaction process (Table 1, entries 7ꢀ12). (iii) A lower temperature led to a
decreased yield (Table 1, entries 5ꢀ6). (iv) Both the base and O2 were found to be
indispensable (Table 1, entries 13ꢀ14). (v) Other oxidants, such as TBHP, DTBP,
H2O2, K2S2O8, pꢀBQ and DDQ, have been examined, however, they did not enhance
the yield of the target product and O2 was found to be an efficient green oxidant
(Table 1, entries 15ꢀ20). (vi) The yields of 3aa with other solvents such as DMF,
toluene, and dioxane were lower than that of DMSO (Table 1, entries 21ꢀ23). Overall,
3aa was successfully formed in 85% GC yield under the optimized conditions
[Cs2CO3 (2 equiv), O2 (1 atm) in DMSO at 120 oC] (Table 1, entry 4).
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The reaction generality and the scope of the metalꢀfree reaction process were next
explored under the optimized conditions. As summarized in Table 2, various amidines
were employed as simple synthetic blocks to react with allylbenzenes to generate an
array of 2,4ꢀdisubstituted pyrimidines. Generally, arylamidines bearing either
electronꢀdonating or electronꢀwithdrawing groups are efficient substrates, providing
the desired products (3aaꢀ3la) in good yields. Gratifyingly, moderate yield of 3ea was
observed when 4ꢀnitrobenzimidamide was used in this amidination reaction.
Isonicotinamidine, nicotinamidine and picolinamidine could also be transformed in
combination with allylbenzene into the desired products (3ma–3oa) in moderate
yields upon isolation. Nonꢀaromatic amidines were also tolerated well, delivering the
desired products (3pa–3sa) in moderate yields. It is noteworthy that an important
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pharmaceutical intermediate (3ra)2c,31 was successfully obtained from guanidine and
allylbenzene. This transformation provides an opportunity for further selective
functionalization at amino group in pharmaceuticals/agrochemicals design and
screening. However, for 2ꢀphenoxyacetamidine, only 29% yield of the desired product
(3ta) was obtained.
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Table 2. Substrate Scope of Amidinesa
a Reaction conditions: Unless otherwise noted, all reactions were performed with 1
(0.25 mmol), 2a (0.30 mmol) and base (2 equiv) in 1.0 mL DMSO under O2
atmosphere for 24 h. bYields of isolated products.
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The scope of the allylic substrates is also crucial for extensive utility of this
amidination method. With the same optimized conditions, the generality of the aryl
allylic substrates is summarized in Table 3. The reactions involving paraꢀ, metaꢀ, and
orthoꢀsubstituted allylbenzenes were found to give the desired products in good yields
(3abꢀ3ak). But the substrate with electronꢀdonating substituent was less reactive than
that with electronꢀwithdrawing substituent in this transformation. Moreover,
disubstituted and trisubstituted allylbenzenes were applicable to this transformation,
affording the desired products in moderate yields (3alꢀ3an). Interestingly, to the
allylbenzene derivatives with more than one allylic group, the reaction only occurred
on one aryl allylic group because of conjugative effect and the other remained
(3aoꢀ3ap). Heteroarylꢀsubstituted propenes such as 2ꢀallylfuran (2q) and
2ꢀallylthiophene (2r) also produced the desired products in fair yields. To our delight,
1ꢀnaphthylpropene could transfer to the corresponding product in 53% yield (3as).
Interestingly, the transformation of (2ꢀmethylallyl)benzene proceeded efficiently
under the optimized conditions and afforded the desired product (3at) in a moderate
yield. In particular, the substitution by benzyl groups at αꢀ and γꢀposition of the
terminal alkene delivered the products (3au) in 81% yield, which might be attributed
to the formation of macro πꢀconjugation systems, promoting the amidination
process.32 Moreover, the substitution by CH3 at γꢀposition of the
(E)ꢀbutꢀ2ꢀenꢀ1ꢀylbenzene (2v) generated the desired products (3av) in moderate yield.
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However,
the
substitution
by
benzyl
group
at
βꢀposition
of
propꢀ2ꢀeneꢀ1,2ꢀdiyldibenzene afforded a trace of products owing to the steric effect.
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a
Table 3. Substrate Scope of Aryl Allylic Substrates
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R3
N
R2
R1
NH
N
O2 (1 atm)
R1
R3
+
NH2 HCl
Cs2CO3 (2 equiv)
DMSO, 120 oC, 24 h
R2
8
1a
2
3 yieldb
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R'
N
N
N
O
N
N
N
R'
Cl
3ab
: R' = F, 76%
3ac: R' = CF3, 78%
3ad: R' = Cl, 73%
3ag: 69%
3ah: R' = CH3, 61%
3ai: R' = C2H5, 59%
3aj: R' = dodecyl, 49%
3ae: R' = C(CH3)3, 71%
3ak
: R' = CH2CH2Ph, 45%
3af
: R' = OCH3, 63%
N
N
N
N
OCH3
N
N
OCH3
OCH3
OCH3
OCH3
3am: 62%
3al: 68%
3an
: 56%
N
N
N
OCH3
O
OCH3
O
N
OCH3
OCH3
3ao:56%
3ap: 51%
N
N
N
N
N
N
S
O
3aq
3ar
: 43%
: 41%
3as: 53%
N
N
N
N
N
N
3at: 61%
3av: 58%
3au: 81%
aReaction conditions: All reactions were performed with 1a (0.25 mmol), 2 (0.3 mmol) and
Cs2CO3 (2 equiv) in 1.0 mL DMSO under O2 atmosphere (1 atm) for 24 h. Isolated yield based on
2a.
Furthermore, nonꢀarylꢀallylic compounds 2w and 2x were also reacted with 1a to
give the same product 2ꢀphenylpyrimidine (3aw). These reactions likely proceed
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through a different mechanism, involving nucleophilic substitution and then
oxidationꢀaminationꢀcyclization processes (Scheme 2). The alkylꢀ or cyclicꢀallylic
compounds were examined and found that they were not suitable substrates for the
reaction under current conditions.
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Scheme 2. Scope of Non-aryl-allylic Compounds
Several control experiments were conducted to gain more insight into the
mechanism of this unique reaction. In the presence of 1,1ꢀdiphenylethylene (DPE)
under the standard reaction conditions, the yield of 3aa dropped to 14%. Moreover,
when 2,6ꢀdiꢀtertꢀbutylꢀ4ꢀmethylphenol (BHT) was added, no 3aa could be detected.
These results suggested that a possible radical pathway should be involved (Scheme 3,
a). Furthermore, Nꢀcinnamylbenzimidamide (4) was used as the substrate under the
same conditions, and the desired product (3aa) was obtained in 83% yield, indicating
that 4 might be a reasonable intermediate (Scheme 3, b).
Scheme 3. Mechanistic Studies
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Based on the aboveꢀmentioned experimental observations and previous reports,33
we propose a possible mechanism for the reaction shown in Scheme 4. This
mechanism involves (i) deprotonation of benzamidine under strong basic conditions
to give intermediate A; (ii) oxidation of A by O2 via a singleꢀelectron transfer (SET)
process to deliver a superoxide anion radical and benzamidinyl radical intermediate B;
(iii) oxidation of 2a through abstracting a benzylic hydrogen to generate a highly
stabilized benzylic/allylic radical, which then undergoes coupling with the
intermediate
B
to
give
4;
(iv) intermediate
4
undergoes
the
deprotonationꢀoxidationꢀaddition and aromatization process to afford the desired
product 3aa.
Scheme 4. Proposed Mechanism
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NH
NH2
NH
NH
NH2
O2
SET
O2
Cs2CO3
[Cs2HCO3]+
NH-
B
A
1a
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[O]
B
2a
2a
2a'
NH
O2
Cs2CO3
N
3aa
H
4
CONCLUSION
In conclusion, this protocol realizes a baseꢀpromoted intermolecular oxidation
amidination reaction of allylic compounds with amidines under oxygen atmosphere.
This observation provides a novel route for the oxidation amidination C(sp3)ꢀH and
C(sp2)ꢀH bonds of allylic compounds simultaneously using protectingꢀgroup free
nitrogen sources. This transformation enables the synthesis of a wide variety of
polysubstituted pyrimidines, and prevents the use of toxic metals or
overstoichiometric amount of oxidants, which also shows high atom economy, good
functional group tolerance and environmental advantages.
EXPERIMENTAL SECTION
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. IR spectra were obtained with an infrared spectrometer on either
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potassium bromide pellets or liquid films between two potassium bromide pellets.
GC−MS data were obtained using electron ionization. HRMS was carried out on a
highꢀresolution mass spectrometer. 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 Synthesis of Polysubstituted Pyrimidines. A mixture of
amidines (0.25 mmol), allylic compounds (0.30 mol) and Cs2CO3 (0.50 mmol, 2
equiv) was stirred in DMSO (1.0 mL) under 1 atm O2 atmosphere at 120 oC for 24 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).
o
2,4-Diphenylpyrimidine (3aa).34 Yield: 75% (43 mg); white solid, mp 63ꢀ65 C; IR
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(KBr) 3064, 1563, 1422, 1383, 1182, 1068, 1030, 747, 691; H NMR (400 MHz,
CDCl3) δ 8.78ꢀ8.77 (m, 1H), 8.59ꢀ8.58 (m, 2H), 8.19ꢀ8.18 (m, 2H), 7.52ꢀ7.49 (m, 7H);
13C NMR (100 MHz, CDCl3) δ 164.6, 163.9, 157.9, 137.9, 137.0, 131.0, 130.8, 129.0,
128.6, 128.4, 127.2, 114.5; MS (EI, 70 eV) m/z: 232.13, 129.11, 116.16, 102.08;
HRMS (ESI) m/z: calcd for C16H13N2 [M+H]+, 233.1073; found, 233.1070.
2-(4-Fluorophenyl)-4-phenylpyrimidine (3ba).35 Yield: 78% ( 49 mg), white solid,
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mp 72ꢀ74 C; IR (KBr) 3064, 1601, 1566, 1433, 1403, 1224, 1187, 1066, 1037, 841,
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768, 691; H NMR (400 MHz, CDCl3) δ 8.78ꢀ8.77 (m, 1H), 8.59ꢀ8.58 (m, 2H),
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8.19ꢀ8.18 (m, 2H), 7.54ꢀ7.51 (m, 4H), 7.19ꢀ7.15 (m, 2H); C NMR (100 MHz,
CDCl3) δ 164.8 (d, J = 249 Hz), 163.9, 163.7, 157.9, 136.9, 134.1 (d, J = 3 Hz), 131.1,
130.4 (d, J = 9 Hz), 129.0, 127.2, 115.5 (d, J = 21 Hz), 114.4; MS (EI, 70 eV) m/z:
250.14, 129.13, 121.09, 102.10; HRMS (ESI) m/z: calcd C16H12FN2 [M+H]+,
251.0979; found, 251.0977.
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2-(4-Chlorophenyl)-4-phenylpyrimidine (3ca).36 Yield: 73% (48 mg), white solid,
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mp 117ꢀ119 C; IR (KBr) 3050, 1601, 1566, 1437, 1354, 1089, 841, 767, 693; H
NMR (400 MHz, CDCl3) δ 8.79ꢀ8.77 (d, 1H, J = 8.0 Hz), 8.52ꢀ8.50 (d, 2H, J = 8.0
Hz), 8.19ꢀ8.18 (m, 2H), 7.54ꢀ7.45 (m, 6H); 13C NMR (100 MHz, CDCl3) δ 164.0,
163.6, 157.9, 136.9, 136.8, 136.4, 131.1, 129.7, 129.0, 128.8, 127.2, 114.7; MS (EI,
70 eV) m/z: 266.11, 137.04, 129.10, 115.13, 102.08; HRMS (ESI) m/z: calcd
C16H12ClN2 [M+H]+, 267.0684; found, 267.0685.
2-(4-Bromophenyl)-4-phenylpyrimidine (3da). 37 Yield: 78% (49 mg), white solid,
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mp 151ꢀ153 C; IR (KBr) 3053, 1601, 1547, 1432, 1370, 1070, 836, 767, 693; H
NMR (400 MHz, CDCl3) δ 8.78ꢀ8.77 (m, 1H), 8.45ꢀ8.43 (d, 2H, J = 8.0 Hz),
8.19ꢀ8.18 (m, 2H), 7.63ꢀ7.52 (m, 6H); 13C NMR (100 MHz, CDCl3) δ 164.0, 163.7,
157.9, 136.8, 136.7, 131.7, 131.1, 129.9, 129.0, 127.2, 125.5, 114.8; MS (EI, 70 eV)
m/z: 310.07, 231.17, 181.01, 155.06, 129.13, 102.10; HRMS (ESI) m/z: calcd
C16H12BrN2 [M+H]+, 311.0178; found, 311.0182.
2-(4-Nitrophenyl)-4-phenylpyrimidine (3ea). Yield: 42% (29 mg), yellow solid, mp
223ꢀ225 C; IR (KBr) 3064, 1636, 1547, 1412, 1348, 1036, 852, 739; 1H NMR (400
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MHz, CDCl3) δ 8.89ꢀ8.88 (m, 1H), 8.77ꢀ8.74 (m, 2H), 8.36ꢀ8.34 (d, J = 8.0 Hz, 2H),
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8.22ꢀ8.21 (m, 2H), 7.70ꢀ7.69 (m, 1H), 7.57ꢀ7.56 (m, 3H); C NMR (100 MHz,
CDCl3) δ 164.3, 162.5, 158.1, 149.3, 143.6, 136.4, 131.4, 129.2, 129.1, 127.3, 123.7,
115.6; MS (EI, 70 eV) m/z: 277.16, 247.17, 231.16, 207.10, 129.11, 102.08; HRMS
(ESI) m/z: calcd C16H12N3O2 [M+H]+, 278.0924; found, 278.0925.
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4-Phenyl-2-(p-tolyl)pyrimidine (3fa).36 Yield: 72% (44 mg), white solid, mp 85ꢀ87
oC; IR (KBr) 3064, 2954, 1549, 1432, 1373, 1068, 833, 766, 693; 1H NMR (400 MHz,
CDCl3) δ 8.72ꢀ8.71 (m, 1H), 8.48ꢀ8.46 (d, J = 8.0 Hz, 2H), 8.16ꢀ8.15 (m, 2H),
7.46ꢀ7.45 (m, 4H), 7.30ꢀ7.28 (d, J = 8.0 Hz, 2H), 2.40 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 164.7, 163.8, 157.8, 141.0, 137.1, 135.2, 130.9, 129.4, 129.0, 128.3, 127.2,
114.3, 21.6; MS (EI, 70 eV) m/z: 246.18, 129.12, 117.12, 102.10; HRMS (ESI) m/z:
calcd C17H15N2 [M+H]+, 247.1230; found, 247.1230.
2-(4-Methoxyphenyl)-4-phenylpyrimidine (3ga).35 Yield: 61% (40 mg), white solid,
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mp 83ꢀ85 C; IR (KBr) 3015, 2838, 1603, 1510, 1402, 1302, 1250, 1170, 1028, 821,
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771, 693; H NMR (400 MHz, CDCl3) δ 8.62ꢀ8.60 (d, 1H, J = 8.0 Hz), 8.54ꢀ8.52 (d,
2H, J = 8.0 Hz), 8.09ꢀ8.08 (m, 2H), 7.40ꢀ7.39 (m, 3H), 7.32ꢀ7.31 (m, 1H), 6.98ꢀ6.95
(d, 2H, J = 8.0 Hz); 13C NMR (100 MHz, CDCl3) δ 164.3, 163.5, 162.0, 157.8, 137.0,
130.9, 130.9, 130.0, 128.9, 127.2, 113.9, 113.8, 55.3; MS (EI, 70 eV) m/z: 262.15,
247.13, 219.15, 133.12, 102.11; HRMS (ESI) m/z: calcd C17H15N2O [M+H]+,
263.1179; found, 263.1177.
2-(3-Bromophenyl)-4-phenylpyrimidine (3ha).37 Yield: 63% (49 mg), yellow liquid;
IR (KBr) 3058, 1549, 1438, 1367, 1069, 842, 761, 686; 1H NMR (400 MHz, CDCl3) δ
8.68ꢀ8.65 (m, 2H), 8.45ꢀ8.43 (d, J = 8.0 Hz, 1H), 8.08ꢀ8.07 (m, 2H), 7.56ꢀ7.54 (d, J
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= 8.0 Hz, 1H), 7.44ꢀ7.41 (m, 4H), 7.31ꢀ7.27 (t, J = 8.0 Hz, 1H); 13C NMR (100 MHz,
CDCl3) δ 163.8, 163.0, 157.8, 139.9, 136.5, 133.6, 131.3, 131.2, 130.1, 129.0, 127.2,
126.9, 122.9, 114.9; MS (EI, 70 eV) m/z: 310.06, 231.06129.12, 115.26, 102.09;
HRMS (ESI) m/z: calcd C16H12BrN2 [M+H]+, 311.0178; found, 311.0178.
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4-Phenyl-2-(m-tolyl)pyrimidine (3ia). Yield: 68% (42 mg), colorless liquid; IR (KBr)
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3052, 2928, 1641, 1568, 1436, 1367, 1065, 1036, 962, 852, 764, 693; H NMR (400
MHz, CDCl3) δ 8.72ꢀ8.71 (m, 1H), 8.39ꢀ8.38 (m, 2H), 8.15ꢀ8.14 (m, 2H), 7.44ꢀ7.36
(m, 5H), 7.28ꢀ7.26 (m, 1H), 2.44 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 164.8, 163.8,
157.8, 138.2, 137.9, 137.0, 131.6, 131.0, 129.0, 128.5, 127.3, 125.6, 114.5, 21.6; MS
(EI, 70 eV) m/z: 246.03, 129.02, 117.01, 102.01; HRMS (ESI) m/z: calcd C17H15N2
[M+H]+, 247.1230; found, 247.1234.
2-(3-Methoxyphenyl)-4-phenylpyrimidine (3ja).37 Yield: 71% (46 mg), colorless
liquid; IR (KBr) 3057, 2954, 1641, 1565, 1433, 1376, 1280, 1229, 1073, 1040, 844,
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765, 689; H NMR (400 MHz, CDCl3) δ 8.75 (s, 1H), 8.20ꢀ8.14 (m, 4H), 7.47ꢀ7.39
(m, 5H), 7.04ꢀ7.02 (d, J = 8.0 Hz, 1H) 3.89 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
164.3, 163.8, 160.0, 157.8, 139.4, 136.9, 131.0, 129.6, 129.0, 127.2, 120.9, 117.0,
114.6, 113.2, 55.4; MS (EI, 70 eV) m/z: 261.15, 232.17, 131.16, 103.11; HRMS (ESI)
m/z: calcd C17H15N2O [M+H]+, 263.1179; found, 263.1180.
2-(2-Chlorophenyl)-4-phenylpyrimidine (3ka).38 Yield: 74% (49 mg), white solid,
mp 70ꢀ72 oC; IR (KBr) 3053, 1619, 1540, 1437, 1365, 1072, 848, 754, 692; 1H NMR
(400 MHz, CDCl3) δ 8.85ꢀ8.83 (d, J = 8.0 Hz, 1H), 8.16ꢀ8.15 (m, 2H), 7.87ꢀ7.85 (d, J
= 8.0 Hz, 1H), 7.62ꢀ7.60 (d, J = 8.0 Hz, 1H), 7.50ꢀ7.47 (m, 4H), 7.36ꢀ7.35 (m, 2H);
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13C NMR (100 MHz, CDCl3) δ 165.5, 164.0, 157.7, 138.0, 136.6, 133.0, 132.0, 131.2,
130.7, 130.5, 129.0, 127.4, 126.8, 114.7; MS (EI, 70 eV) m/z: 266.12, 231.15, 137.05,
129.11, 102.09; HRMS (ESI) m/z: calcd C16H12ClN2 [M+H]+, 267.0684; found,
267.0686.
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4-Phenyl-2-(o-tolyl)pyrimidine (3la).37 Yield: 62% (38 mg), colorless oil; IR (KBr)
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3056, 2959, 1642, 1559, 1426, 1374, 1068, 1039, 926, 844, 752, 692; H NMR (400
MHz, CDCl3) δ 8.80ꢀ8.79 (m, 1H), 8.15ꢀ8.14 (m, 2H), 7.97ꢀ7.96 (m, 1H), 7.53ꢀ7.46
(m, 4H), 7.33ꢀ7.31 (m, 3H), 2.65 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 167.6, 163.5,
157.7, 138.4, 137.5, 136.9, 131.5, 131.0, 130.8, 129.5, 129.0, 127.3, 126.0, 113.9,
21.6; MS (EI, 70 eV) m/z:245.18, 168.15, 121.62, 103.12; HRMS (ESI) m/z: calcd
C17H15N2 [M+H]+, 247.1230; found, 247.1233.
4-Phenyl-2-(pyridin-4-yl)pyrimidine (3ma).37 Yield: 67% (39 mg), yellow solid, mp
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118ꢀ120 C; IR (KBr) 3062, 1709, 1642, 1607, 1578, 1549, 1421, 1383, 1058, 838,
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795, 691; H NMR (400 MHz, CDCl3) δ 8.81ꢀ8.77 (m, 3H), 8.38ꢀ8.37 (m, 2H),
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8.18ꢀ8.17 (m, 2H), 7.63ꢀ7.62 (m, 1H), 7.52ꢀ7.51 (m, 3H); C NMR (100 MHz,
CDCl3) δ 164.1, 162.5, 158.0, 150.4, 145.1, 136.3, 131.3, 129.0, 127.2, 122.1, 115.9;
MS (EI, 70 eV) m/z: 233.14, 205.15, 129.12, 102.11; HRMS (ESI) m/z: calcd
C15H12N3 [M+H]+, 234.1026; found, 234.1029.
4-Phenyl-2-(pyridin-3-yl)pyrimidine (3na). Yield: 63% (37 mg), yellow solid, mp
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78ꢀ81 C; IR (KBr) 3055, 1715, 1645, 1565, 1544, 1428, 1373, 1037, 829, 794, 694;
1H NMR (400 MHz, CDCl3) δ 9.76 (s, 1H), 8.79ꢀ8.71 (m, 3H), 8.17ꢀ8.16 (m, 2H),
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7.58ꢀ7.57 (m, 1H), 7.51ꢀ7.50 (m, 3H), 7.42ꢀ7.39 (m, 1H); C NMR (100 MHz,
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CDCl3) δ 163.9, 162.8, 157.9, 151.3, 150.0, 136.4, 135.5, 133.3, 131.2, 129.0, 127.2,
123.3, 115.1; MS (EI, 70 eV) m/z: 233.15, 207.15, 129.13, 102.13; HRMS (ESI) m/z:
calcd C15H12N3 [M+H]+, 234.1026; found, 234.1029.
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4-Phenyl-2-(pyridin-2-yl)pyrimidine (3oa). Yield: 61% (35 mg), yellow solid, mp
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65ꢀ67 C; IR (KBr) 3058, 1710, 1643, 1565, 1422, 1382, 1065, 854, 787, 693; H
NMR (400 MHz, CDCl3) δ 8.87ꢀ8.83 (m, 2H), 8.61ꢀ8.59 (d, J = 8.0 Hz, 1H),
8.14ꢀ8.13 (m, 2H), 7.81ꢀ7.77 (m, 1H), 7.57ꢀ7.56 (m, 1H), 7.45ꢀ7.43 (m, 3H),
7.33ꢀ7.32 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 163.9, 163.4, 158.3, 154.8, 149.8,
136.7, 136.3, 131.0, 128.8, 127.1, 124.7, 123.5, 115.6; MS (EI, 70 eV) m/z: 233.16,
205.13, 129.12, 102.13; HRMS (ESI) m/z: calcd C15H11N3Na [M+Na]+, 256.0845;
found, 256.0850.
2-Methyl-4-phenylpyrimidine (3pa).36 Yield: 34% (15 mg), white solid, mp 55ꢀ56
oC; IR (KBr) 3052, 2954, 1641, 1577, 1548, 1436, 1360, 1315, 1206, 1042, 843, 749,
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692; H NMR (400 MHz, CDCl3) δ 8.68ꢀ8.65 (m, 1H), 8.06ꢀ8.05 (m, 2H), 7.49ꢀ7.48
(m, 4H), 2.80 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 168.4, 164.1, 157.4, 136.9,
130.8, 128.9, 127.2, 114.0, 26.3; MS (EI, 70 eV) m/z: 170.15, 129.12, 102.10; HRMS
(ESI) m/z: calcd C11H11N2 [M+H]+, 171.0917; found, 171.0920.
N-Methyl-4-phenylpyrimidin-2-amine (3qa). Yield: 57% (26 mg), white solid, mp
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98ꢀ101 C; IR (KBr) 3416, 3052, 2953, 1642, 1558, 1455, 1342, 816; H NMR (400
MHz, CDCl3) δ 8.34ꢀ8.33 (m, 1H), 8.03ꢀ8.02 (m, 2H), 7.46ꢀ7.45 (m, 3H), 6.96ꢀ6.95
(m, 1H), 5.44 (s, 1H), 3.06ꢀ3.04 (m, 3H); 13C NMR (100 MHz, CDCl3) δ 164.9, 163.2,
158.4, 137.5, 130.5, 128.7, 127.0, 106.3, 28.4; MS (EI, 70 eV) m/z: 185.15, 156.13,
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129.10; HRMS (ESI) m/z: calcd C11H12N3 [M+H]+, 186.1026; found, 186.1029.
4-Phenylpyrimidin-2-amine (3ra).39 Yield: 73% (31 mg), white solid, mp 160ꢀ161
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oC; IR (KBr) 3420, 3056, 1641, 1557, 1434, 1370, 1061, 854; H NMR (400 MHz,
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CDCl3) δ 8.26ꢀ8.25 (m, 1H), 7.92ꢀ7.91 (m, 2H), 7.40ꢀ7.39 (m, 3H), 6.96ꢀ6.95 (m, 1H),
5.30 (s, 2H); 13C NMR (100 MHz, CDCl3) δ 165.6, 163.3, 158.6, 137.2, 130.6, 128.8,
127.1, 107.7; MS (EI, 70 eV) m/z: 170.03, 155.01, 128.03, 102.99; HRMS (ESI) m/z:
calcd C10H10N3 [M+H]+, 172.0869; found,172.0873.
2-Cyclopropyl-4-phenylpyrimidine (3sa).37 Yield: 39% (19 mg), pale yellow oil; IR
(KBr) 3063, 2955, 2885, 1645, 1575, 1495, 1442, 1414, 1376, 1186, 1062, 960, 841,
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767, 696; H NMR (400 MHz, CDCl3) δ 8.57ꢀ8.56 (m, 1H), 8.06ꢀ8.05 (m, 2H),
7.46ꢀ7.40 (m, 4H), 2.33ꢀ2.32 (m, 1H), 1.23ꢀ1.22 (m, 2H), 1.09ꢀ1.07 (m, 2H); 13C
NMR (100 MHz, CDCl3) δ 172.1, 163.5, 157.2, 137.0, 130.7, 128.8, 127.1, 113.4,
18.4, 10.8; MS (EI, 70 eV) m/z: 195.14, 170.14, 129.13, 103.12; HRMS (ESI) m/z:
calcd C13H13N2 [M+H]+, 197.1073; found, 197.1075.
2-(Phenoxymethyl)-4-phenylpyrimidine (3ta). Yield: 29% (19 mg), pale yellow oil;
IR (KBr) 3078, 2923, 2851, 1640, 1577, 1493, 1408, 1311, 1070, 921, 842, 782, 621;
1H NMR (400 MHz, CDCl3) δ 8.80ꢀ8.79 (m, 1H), 8.09ꢀ8.08 (m, 2H), 7.62ꢀ7.61 (m,
1H), 7.51ꢀ7.50 (m, 3H), 7.30ꢀ7.26 (m, 2H), 7.07ꢀ7.05 (m, 2H), 6.96ꢀ6.94 (m, 1H),
5.38 (s, 2H); 13C NMR (100 MHz, CDCl3) δ 166.3, 164.4, 158.6, 158.1, 136.4, 131.2,
129.4, 129.0, 127.3, 121.1, 115.5, 115.0, 70.9; MS (EI, 70 eV) m/z: 262.19, 245.15,
233.18, 185.14, 156.13, 130.14, 115.12, 103.12; HRMS (ESI) m/z: calcd C17H15N2O
[M+H]+, 263.1179; found, 263.1176.
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4-(4-Fluorophenyl)-2-phenylpyrimidine (3ab).35 Yield: 76% (47 mg), yellow solid,
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mp 55ꢀ56 C; IR (KBr) 3065, 1641, 1563, 1426, 1378, 1069, 1034, 829, 758, 694; 1H
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NMR (400 MHz, CDCl3) δ 8.53ꢀ8.52 (m, 1H), 8.41ꢀ8.40 (m, 2H), 7.96ꢀ7.95 (m, 2H),
7.33ꢀ7.32 (m, 3H), 7.20 (s, 1H), 6.99ꢀ6.95 (m, 2H); 13C NMR (100 MHz, CDCl3) δ
164.7 (d, J = 250 Hz), 164.5, 162.6, 137.6, 133.0 (d, J = 3 Hz), 130.8, 129.2 (d, J = 8
Hz), 128.6, 128.4, 115.9 (d, J = 22 Hz), 114.0; MS (EI, 70 eV) m/z: 250.16, 147.12,
120.09, 103.11; HRMS (ESI) m/z: calcd C16H12FN2 [M+H]+, 251.0979; found,
251.0979.
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2-Phenyl-4-(4-(trifluoromethyl)phenyl)pyrimidine (3ac).37 Yield: 78% (58 mg),
yellow solid, mp 75ꢀ77 oC; IR (KBr) 3054, 1641, 1557, 1432, 1371, 1327, 1121, 1069,
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830, 761, 695; H NMR (400 MHz, CDCl3) δ 8.76ꢀ8.75 (m, 1H), 8.54ꢀ8.53 (m, 2H),
8.21ꢀ8.19 (d, 2H, J = 8.0 Hz), 7.71ꢀ7.69 (d, 2H, J = 8.0 Hz), 7.48ꢀ7.44 (m, 4H); 13C
NMR (100 MHz, CDCl3) δ 163.5 (d, J = 250 Hz), 158.2, 140.2, 137.5, 132.5 (dd, J =
33 Hz, J = 97 Hz), 131.0, 128.6, 128.4, 127.5, 125.8 (dd, J = 3 Hz, J = 11 Hz), 125.4,
122.7, 114.7; MS (EI, 70 eV) m/z: 300.15, 197.11, 170.11, 150.14, 120.11, 103.10;
HRMS (ESI) m/z: calcd C17H12F3N2 [M+H]+, 301.0947; found, 301.0954.
4-(4-Chlorophenyl)-2-phenylpyrimidine (3ad).36 Yield: 73% (49 mg), yellow solid,
o
mp 70ꢀ71 C; IR (KBr) 3089, 1719, 1642, 1565, 1420, 1384, 1089, 1065, 826, 759,
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646; H NMR (400 MHz, CDCl3) δ 8.83ꢀ8.82 (m, 1H), 8.56ꢀ8.55 (m, 2H), 8.17ꢀ8.14
(m, 2H), 7.54ꢀ7.48 (m, 6H); 13C NMR (100 MHz, CDCl3) δ 164.7, 162.7, 158.0, 137.6,
137.3, 135.4, 130.9, 129.2, 128.6, 128.5, 128.3, 114.2; MS (EI, 70 eV) m/z: 265.99,
231.03, 163.00, 135.95, 103.01; HRMS (ESI) m/z: calcd C16H12ClN2 [M+H]+,
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267.0684; found, 267.0687.
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4-(4-(tert-Butyl)phenyl)-2-phenylpyrimidine (3ae). Yield: 71% (51 mg), colorless
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oil; IR (KBr) 3062, 2960, 1612, 1567, 1427, 1379, 1068, 1033, 854, 787, 693; H
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NMR (400 MHz, CDCl3) δ 8.77ꢀ8.76 (m, 1H), 8.59ꢀ8.58 (m, 2H), 8.15ꢀ8.13 (d, 2H, J
= 8.0 Hz), 7.52ꢀ7.49 (m, 6H), 1.36 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 164.5,
163.9, 157.7, 154.5, 138.0, 134.2, 130.7, 128.6, 128.3, 127.0, 125.9, 114.3, 34.9, 31.3;
MS (EI, 70 eV) m/z: 288.23, 273.20, 245.18, 122.62; HRMS (ESI) m/z: calcd
C20H21N2 [M+H]+, 289.1699; found, 289.1698.
4-(4-Methoxyphenyl)-2-phenylpyrimidine (3af).37 Yield: 63% (41 mg), white solid,
mp 87ꢀ89 oC; IR (KBr) 3070, 2957, 2844, 1611, 1568, 1511, 1418, 1384, 1285, 1251,
1030, 828, 760, 695; 1H NMR (400 MHz, CDCl3) δ 8.74ꢀ8.73 (m, 1H), 8.58ꢀ8.56 (d, J
= 8.0 Hz, 2H), 8.19ꢀ8.17 (d, J = 8.0 Hz, 2H), 7.51ꢀ7.49 (m, 4H), 7.02ꢀ7.00 (d, J = 8.0
Hz, 2H), 3.86 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 164.4, 163.4, 162.1, 157.5,
138.0, 130.6, 129.4, 128.8, 128.5, 128.3, 114.3, 113.7, 55.4; MS (EI, 70 eV) m/z:
262.16, 247.14, 219.14, 159.13, 132.12, 117.09, 103.09; HRMS (ESI) m/z: calcd
C17H15N2O [M+H]+, 263.1179; found, 263.1178.
4-(3-Chlorophenyl)-2-phenylpyrimidine (3ag).37 Yield: 69% (46 mg), yellow oil; IR
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(KBr) 3069, 1640, 1559, 1479, 1421, 1380, 1072, 1033, 929, 844, 792, 755, 692; H
NMR (400 MHz, CDCl3) δ 8.73ꢀ8.72 (m, 1H), 8.54ꢀ8.52 (m, 2H), 8.14 (s, 1H),
7.95ꢀ7.93 (m, 1H), 7.48ꢀ7.32 (m, 6H); 13C NMR (100 MHz, CDCl3) δ 164.6, 162.3,
158.1, 138.7, 137.6, 135.1, 130.9, 130.9, 130.1, 128.6, 128.4, 127.3, 125.2, 114.5; MS
(EI, 70 eV) m/z: 265.97, 231.03, 162.99, 135.96, 103.02; HRMS (ESI) m/z: calcd
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C16H12ClN2 [M+H]+, 267.0684; found, 267.0683.
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4-(2-Methoxyphenyl)-2-phenylpyrimidine (3ah).37 Yield: 61% (40 mg), pale yellow
oil; IR (KBr) 3061, 2953, 1561, 1490, 1425, 1377, 1257, 1182, 1062, 1027, 843, 751,
696, 620; 1H NMR (400 MHz, CDCl3) δ 8.74ꢀ8.73 (m, 1H), 8.57ꢀ8.55 (d, 2H, J = 8.0
Hz), 8.24ꢀ8.22 (d, 1H, J = 8.0 Hz), 7.84ꢀ7.83 (m, 1H), 7.48ꢀ7.38 (m, 4H), 7.12ꢀ7.09
(m, 1H), 6.96ꢀ6.94 (m, 1H), 3.83 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 164.3, 162.6,
158.3, 156.8, 138.2, 131.8, 131.3, 130.5, 128.5, 128.2, 126.4, 121.2, 119.7, 111.6,
56.0; MS (EI, 70 eV) m/z: 262.16, 233.17, 157.12, 130.12, 103.06; HRMS (ESI) m/z:
calcd C17H15N2O [M+H]+, 263.1179; found, 263.1180.
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4-(2-Ethoxyphenyl)-2-phenylpyrimidine (3ai). Yield: 59% (41 mg), white solid, mp
77ꢀ79 oC; IR (KBr) 3046, 2929, 1640, 1560, 1539, 1448, 1371, 1260, 1041, 858, 749,
694, 621; 1H NMR (400 MHz, CDCl3) δ 8.75ꢀ8.74 (m, 1H), 8.56 (d, 2H, J = 8.0 Hz),
8.26 (d, 1H, J = 8.0 Hz), 7.91ꢀ7.90 (m, 1H), 7.49ꢀ7.36 (m, 4H), 7.12ꢀ7.10 (m, 1H),
6.95ꢀ6.93 (m, 1H), 4.07 (q, 2H, J = 4.0 Hz), 1.40 (t, 3H, J = 4.0 Hz); 13C NMR (100
MHz, CDCl3) δ 164.3, 162.7, 157.7, 156.8, 138.3, 131.8, 131.3, 130.5, 128.5, 128.2,
126.3, 121.0, 119.6, 112.5, 64.2, 14.9; MS (EI, 70 eV) m/z: 276.02, 260.99, 232.04,
220.02, 157.04, 129.03, 103.01, 89.00; HRMS (ESI) m/z: calcd C18H16N2NaO
[M+Na]+, 299.1155; found, 299.1158.
4-(2-(Dodecyloxy)phenyl)-2-phenylpyrimidine (3aj). Yield: 49% (51 mg), yellow
oil; IR (KBr) 3110, 3077, 2926, 2855, 1640, 1563, 1490, 1421, 1382, 1255, 1037, 849,
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749, 694, 621; H NMR (400 MHz, CDCl3) δ 8.77ꢀ8.76 (m, 1H), 8.57ꢀ8.55 (m, 2H),
8.26ꢀ8.24 (m, 1H), 7.92ꢀ7.91 (m, 1H), 7.49ꢀ7.41 (m, 4H), 7.14ꢀ7.11 (m, 1H),
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7.02ꢀ7.00 (m, 1H), 4.07 (t, 2H, J = 4.0 Hz), 1.84ꢀ1.81 (m, 2H), 1.45ꢀ1.43 (m, 2H),
1.27ꢀ1.25 (m, 16H), 0.88 (t, 3H, J = 4.0 Hz); 13C NMR (100 MHz, CDCl3) δ 164.2,
162.8, 157.8, 156.5, 138.1, 131.7, 131.3, 130.5, 128.5, 128.2, 126.4, 121.0, 119.6,
112.5, 68.7, 31.9, 29.7, 29.6, 29.6, 29.6, 29.4, 29.3, 29.2, 26.2, 22.7, 14.1; MS (EI, 70
eV) m/z: 416.12, 280.98, 261.01, 247.99, 206.97, 126.98; HRMS (ESI) m/z: calcd
C28H36N2NaO [M+Na]+, 439.2720; found, 439.2724.
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4-(2-Phenethoxyphenyl)-2-phenylpyrimidine (3ak). Yield: 45% (39 mg), yellow oil;
IR (KBr) 3064, 3031, 2952, 2880, 1639, 1565, 1544, 1422, 1382, 1257, 1062, 1029,
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853, 749, 698, 622; H NMR (400 MHz, CDCl3) δ 8.59ꢀ8.54 (m, 3H), 8.19ꢀ8.17 (d,
1H, J = 8.0 Hz), 8.49ꢀ8.46 (m, 4H), 7.38ꢀ7.34 (m, 1H), 7.28ꢀ7.20 (m, 5H), 7.10ꢀ7.7
(m, 1H), 6.95ꢀ6.93 (m, 1H), 4.24 (t, 2H, J = 4.0 Hz), 3.05 (t, 2H, J = 4.0 Hz); 13C
NMR (100 MHz, CDCl3) δ 164.3, 162.5, 157.4, 156.7, 138.4, 138.2, 131.7, 131.4,
130.5, 129.1, 128.6, 128.6, 128.3, 126.7, 126.7, 121.3, 119.9, 112.5, 69.2, 35.8; MS
(EI, 70 eV) m/z: 351.06, 261.01, 248.01, 232.04, 219.99, 129.04, 105.03, 77.00;
HRMS (ESI) m/z: calcd C24H20N2NaO [M+Na]+, 375.1468; found, 375.1472.
4-(3,5-Dimethylphenyl)-2-phenylpyrimidine (3al).37 Yield: 68% (44 mg), yellow oil;
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IR (KBr) 3050, 2955, 1617, 1560, 1428, 1367, 1071, 837, 759, 694; H NMR (400
MHz, CDCl3) δ 8.78ꢀ8.77 (m, 1H), 8.58ꢀ8.57 (m, 2H), 7.81ꢀ7.80 (m, 2H), 7.52ꢀ7.51
(m, 4H), 7.15ꢀ7.14 (m, 1H), 2.44 (s, 6H); 13C NMR (100 MHz, CDCl3) δ 164.5, 164.3,
157.6, 138.5, 138.0, 137.0, 132.7, 130.7, 128.5, 128.3, 125.1, 114.7, 21.5; MS (EI, 70
eV) m/z: 260.21, 157.17, 130.15, 103.11; HRMS (ESI) m/z: calcd C18H17N2 [M+H]+,
261.1386; found, 261.1384.
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4-(3,4-Dimethoxyphenyl)-2-phenylpyrimidine (3am).40 Yield: 62% (45 mg), white
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solid, mp 115ꢀ116 C; IR (KBr) 3140, 3079, 2956, 2842, 1642, 1563, 1459, 1421,
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1389, 1224, 1062, 1024, 840, 759, 697; 1H NMR (400 MHz, CDCl3) δ 8.73ꢀ8.72 (m,
1H), 8.56ꢀ8.55 (m, 2H), 7.86 (s, 1H), 7.72ꢀ7.70 (d, J = 8.0 Hz, 1H), 7.50ꢀ7.47 (m, 4H),
6.94ꢀ6.92 (d, J = 8.0 Hz, 1H), 4.01 (s, 3H), 3.92 (s, 3H); 13C NMR (100 MHz, CDCl3)
δ 164.3, 163.3, 157.5, 151.7, 149.4, 138.0, 130.7, 129.6, 128.5, 128.2, 120.4, 113.8,
111.0, 109.9, 56.0, 56.0; MS (EI, 70 eV) m/z: 292.21, 277.18, 246.20, 205.13, 146.14,
103.09; HRMS (ESI) m/z: calcd C18H17N2O2 [M+H]+, 293.1285; found, 293.1284.
2-Phenyl-4-(3,4,5-trimethoxyphenyl)pyrimidine (3an). Yield: 56% (46 mg), white
solid, mp 161ꢀ163 oC; IR (KBr) 3054, 2953, 1640, 1615, 1563, 1432, 1343, 1127, 829,
757, 700; 1H NMR (400 MHz, CDCl3) δ 8.77ꢀ8.76 (m, 1H), 8.56ꢀ8.54 (m, 2H, J = 8.0
Hz), 7.49ꢀ7.44 (m, 6H), 3.97 (s, 6H), 3.93 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
164.4, 163.4, 157.7, 153.6, 140.8, 137.8, 132.3, 130.7, 128.6, 128.2, 114.3, 104.5,
61.0, 56.3; MS (EI, 70 eV) m/z: 322.18, 307.15, 276.18, 249.13, 193.15; HRMS (ESI)
m/z: calcd C19H19N2O3 [M+H]+, 323.1390; found, 323.1391.
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4-(4-(Hex-5-en-1-yloxy)-3,5-dimethoxyphenyl)-2-phenylpyrimidine (3ao). Yield:
56% (55 mg), yellow oil; IR (KBr) 3070, 2934, 2724, 1640, 1587, 1544, 1460, 1423,
1382, 1231, 1071, 1033, 834, 761, 700, 664; 1H NMR (400 MHz, CDCl3) δ 8.80ꢀ8.79
(m, 1H), 8.56ꢀ8.55 (m, 2H), 7.52ꢀ7.51 (m, 4H), 7.46 (s, 2H), 5.90ꢀ5.82 (m, 1H),
5.06ꢀ4.95 (m, 2H), 4.09ꢀ4.06 (m, 2H), 3.97 (s, 6H), 2.16ꢀ2.11(m, 2H), 1.85ꢀ1.78 (m,
2H), 1.65ꢀ1.58 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 164.4, 163.6, 157.7, 153.9,
140.2, 138.8, 137.8, 132.1, 130.8, 128.6, 128.3, 114.5, 114.3, 104.7, 73.4, 56.4, 33.5,
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29.6, 25.2; MS (EI, 70 eV) m/z: 390.29, 308.20, 262.16; HRMS (ESI) m/z: calcd
C24H27N2O3 [M+H]+, 391.2016; found, 391.2016.
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4-(4-(Hept-6-en-1-yloxy)-3,5-dimethoxyphenyl)-2-phenylpyrimidine (3ap). Yield:
51% (52 mg), yellow oil; IR (KBr) 3071, 2934, 2724, 1640, 1549, 1460, 1422, 1383,
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1230, 1071, 1035, 833, 760, 700, 662; H NMR (400 MHz, CDCl3) δ 8.80ꢀ8.79 (m,
1H), 8.57ꢀ8.55 (m, 2H), 7.53ꢀ7.51 (m, 4H), 7.47 (s, 2H), 5.87ꢀ5.78 (m, 1H), 5.04ꢀ4.94
(m, 2H), 4.08ꢀ4.05 (m, 2H), 3.97 (s, 6H), 2.12ꢀ2.07 (m, 2H), 1.82ꢀ1.78 (m, 2H),
1.52ꢀ1.47 (m, 4H); 13C NMR (100 MHz, CDCl3) δ 164.5, 163.6, 157.7, 153.9, 140.3,
139.0, 137.9, 132.1, 130.7, 128.6, 128.3, 114.3, 104.8, 73.6, 56.4, 33.8, 30.0, 28.7,
25.4; MS (EI, 70 eV) m/z: 404.08, 308.02, 262.04, 207.04; HRMS (ESI) m/z: calcd
C25H29N2O3 [M+H]+, 405.2173; found, 405.2176.
4-(Furan-2-yl)-2-phenylpyrimidine (3aq).37 Yield: 41% (23 mg), yellow oil; IR
(KBr) 3107, 1642, 1603, 1563, 1534, 1402, 1370, 1188, 1066, 961, 851, 760, 702; 1H
NMR (400 MHz, CDCl3) δ 8.76ꢀ8.75 (m, 1H), 8.51ꢀ8.50 (m, 1H), 7.48ꢀ7.39 (m, 6H),
6.56ꢀ6.55 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 164.5, 157.8, 155.6, 152.2, 145.0,
136.7, 130.7, 128.5, 128.3, 112.5, 112.4, 112.4; MS (EI, 70 eV) m/z: 222.00, 194.03,
103.01, 92.01; HRMS (ESI) m/z: calcd C14H11N2O [M+H]+, 223.0866; found,
223.0862.
2-Phenyl-4-(thiophen-2-yl)pyrimidine (3ar). Yield: 43% (26 mg), yellow oil; IR
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(KBr) 3072, 1563, 1426, 1386, 1345, 1068, 1036, 833, 756, 700, 626; H NMR (400
MHz, CDCl3) δ 8.73ꢀ8.72 (m, 1H), 8.61ꢀ8.59 (m, 2H), 7.79ꢀ7.78 (m, 1H), 7.56ꢀ7.53
(m, 4H), 7.38ꢀ7.37 (m, 1H), 7.16ꢀ7.14 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 164.5,
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159.0, 157.6, 142.9, 137.5, 130.9, 130.2, 128.6, 128.4, 128.3, 127.5, 112.8; MS (EI,
70 eV) m/z: 237.96, 134.99, 107.96, 103.00; HRMS (ESI) m/z: calcd C14H11N2S
[M+H]+, 239.0637; found, 239.0637.
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4-(Naphthalen-1-yl)-2-phenylpyrimidine (3as).37 Yield: 53% (37 mg), white solid,
mp 154ꢀ156 oC; IR (KBr) 3051, 1640, 1619, 1538, 1430, 1369, 1071, 1033, 849, 776,
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697; H NMR (400 MHz, CDCl3) δ 8.78ꢀ8.77 (m, 1H), 8.58ꢀ8.57 (m, 2H), 8.30ꢀ8.29
(m, 1H), 7.88ꢀ7.84 (m, 2H), 7.63ꢀ7.62 (m, 1H), 7.45ꢀ7.44 (m, 6H), 7.31ꢀ7.30 (m, 1H);
13C NMR (100 MHz, CDCl3) δ 166.8, 164.5, 157.6, 137.9, 136.3, 134.1, 131.0, 130.8,
130.4, 128.8, 128.7, 128.6, 128.2, 127.1, 126.3, 125.4, 125.4, 119.8; MS (EI, 70 eV)
m/z: 281.17, 178.12, 151.13, 103.08; HRMS (ESI) m/z: calcd C20H15N2 [M+H]+,
283.1230; found, 283.1232.
5-Methyl-2,4-diphenylpyrimidine (3at).37 Yield: 61% (38 mg), white solid, mp
o
87ꢀ88 C; IR (KBr) 3059, 2958, 2927, 1642, 1563, 1534, 1423, 1376, 1320, 1181,
1067, 1031, 858, 752, 695; 1H NMR (400 MHz, CDCl3) δ 8.67 (s, 1H), 8.50ꢀ8.49 (m,
2H), 7.74ꢀ7.72 (d, J = 8.0 Hz, 2H), 7.51ꢀ7.46 (m, 6H), 2.42 (s, 3H); 13C NMR (100
MHz, CDCl3) δ 164.9, 162.5, 159.2, 138.5, 137.8, 130.3, 129.3, 129.1, 128.5, 128.4,
128.0, 125.6, 17.1; MS (EI, 70 eV) m/z: 245.17, 142.16, 115.13, 103.10; HRMS (ESI)
m/z: calcd C17H15N2 [M+H]+, 247.1230; found, 247.1230.
2,4,6-Triphenylpyrimidine (3au).34 Yield: 81% (62 mg), white solid, mp 185ꢀ186 oC;
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IR (KBr) 3056, 1642, 1566, 1525, 1442, 1361, 1071, 1031, 859, 735, 678; H NMR
(400 MHz, CDCl3) δ 8.71ꢀ8.69 (m, 2H), 8.22ꢀ8.20 (m, 4H), 7.88 (s, 1H), 7.50ꢀ7.46 (m,
9H); 13C NMR (100 MHz, CDCl3) δ 164.7, 164.5, 138.3, 137.6, 130.8, 130.7, 129.0,
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128.6, 128.5, 127.4, 110.3; MS (EI, 70 eV) m/z: 308.01, 205.05, 102.02; HRMS (ESI)
m/z: calcd C22H17N2 [M+H]+, 309.1386; found, 309.1386.
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4-Methyl-2,6-diphenylpyrimidine (3av).40 Yield: 58% (36 mg), white solid, mp
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o
86ꢀ87 C; IR (KBr) 3054, 2927, 1640, 1571, 1444, 1365, 1063, 1038, 963, 857, 767,
692; 1H NMR (400 MHz, CDCl3) δ 8.58 (d, J = 8.0 Hz, 2H), 8.15 (d, J = 8.0 Hz, 2H),
7.48ꢀ7.45 (m, 6H), 7.36 (s, 1H), 2.57 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 167.8,
164.3, 163.7, 138.2, 137.3, 130.7, 130.5, 128.9, 128.5, 128.4, 127.2, 114.0, 24.6; MS
(EI, 70 eV) m/z: 246.28, 231.21, 143.17, 128.12, 102.11; HRMS (ESI) m/z: calcd
C17H15N2 [M+H]+, 247.1230; found, 247.1230.
2-Phenylpyrimidine (3aw).41 Yield: 57% (22 mg), white solid, mp 36ꢀ37 oC; IR (KBr)
3041, 1641, 1561, 1419, 1366, 1319, 1180, 1068, 1034, 851, 748, 694; 1H NMR (400
MHz, CDCl3) δ 8.78ꢀ8.77 (m, 2H), 8.45ꢀ8.44 (m, 2H), 7.48ꢀ7.47 (m, 3H), 7.14ꢀ7.13
(m, 1H); 13C NMR (100 MHz, CDCl3) δ 164.8, 157.2, 137.6, 130.8, 128.6, 128.2,
119.1; MS (EI, 70 eV) m/z: 156.14, 103.09; HRMS (ESI) m/z: calcd C10H9N2 [M+H]+,
157.0760; found, 157.0758.
Synthesis of N-cinnamylbenzimidamide (4)
To a mixture of benzamidine (1.0 mmol), (E)ꢀ(3ꢀbromopropꢀ1ꢀenꢀ1ꢀyl)benzene (0.5
mmol), K2CO3 (2.0 mmol) was added CH3CN (3.0 mL) in a test tube equipped with a
magnetic stirring bar. The mixture was stirred at room temperature for 12 h. After the
reaction was completed, the residue was directly subjected to silica gel column
chromatography or purification of the mixture on a preparative TLC to afford the
desired product 4. Colorless oil, Yield: 64% (0.075 g); IR (KBr) 3045, 1643, 1548,
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1435, 1379, 1056, 1032, 849, 777, 699; H NMR (400 MHz, CDCl3) δ 7.55ꢀ7.53 (m,
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2H), 7.32ꢀ7.16 (m, 8H), 8.56ꢀ8.52 (m, 1H), 6.31ꢀ6.27 (m, 1H), 5.43 (s, 2H), 4.06ꢀ4.04
(d, J = 8.0 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 163.0, 137.6, 136.9, 131.5, 130.1,
128.7, 128.6, 127.5, 126.6, 126.4, 126.2, 45.1; HRMS (ESI) m/z: calcd C16H17N2
[M+H]+, 237.1386; found, 237.1391.
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ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the ACS Publications
website at DOI: 10.1021/acs.joc.
1H and 13C spectra of all synthesized compounds (PDF)
AUTHOR INFORMATION
Corresponding Author
* Eꢀmail: jianghf@scut.edu.cn
* Eꢀmail: cewuwq@scut.edu.cn
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
We are grateful to the National Natural Science Foundation of China (21420102003
and 21472051), the Fundamental Research Funds for the Central Universities
(2015ZY001), the China Postdoctoral Science Foundation Funded Project
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(2014M562165), and Jiangxi Natural Science Foundation (20133BCB24011,
20141BBG70070 and 20151BAB203011).
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