Copper-Catalyzed Synthesis of Substituted Quinazolines from Benzonitriles and 2-Ethynylanilines via Carbon-Carbon Bond Cleavage Using Molecular Oxygen

Article abstract of DOI:10.1021/acs.joc.8b00378

A copper-catalyzed process for the synthesis of substituted quinazolines from benzonitriles and 2-ethynylanilines using molecular oxygen (O₂) as sole oxidant is described. The mild catalytic system enabled the effective cleavage of the C-C triple bond and construction of new C-N and C-C bonds in one operation. Furthermore, the compound N,N-dimethyl-4-(2-(4-(trifluoromethyl)phenyl)quinazolin-4-yl)aniline (3dj) exhibited obvious aggregation-induced emission phenomenon, and the fluorescence quantum yield (Φ_F,film) and lifetime (τ_film) were measured to be 45.5% and 5.8 ns in thin films state, respectively.

Full text of DOI:10.1021/acs.joc.8b00378

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Copper-Catalyzed Synthesis of Substituted Quinazolines
from Benzonitriles and 2-Ethynylanilines via Carbon-
Carbon Bond Cleavage Using Molecular Oxygen
Xu Wang, Dandan He, Yubing Huang, Qihang Fan, Wanqing Wu, and Huanfeng Jiang
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b00378 • Publication Date (Web): 24 Apr 2018
Downloaded from http://pubs.acs.org on April 24, 2018
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Copper-Catalyzed Synthesis of Substituted Quinazolines
from Benzonitriles and 2-Ethynylanilines via
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Carbon-Carbon Bond Cleavage Using Molecular Oxygen
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Xu Wang,b Dandan He,b Yubing Huang,b Qihang Fan,b Wanqing Wu*,a,b, Huanfeng
Jiang*,b
a. State Key Laboratory of Luminescent Materials and Devices, South China University of Technology, Guangzhou
510640, China
b. Key Laboratory of Functional Molecular Engineering of Guangdong Province, School of Chemistry and
Chemical Engineering, South China University of Technology, Guangzhou 510640, China
Fax: (+86) 20ꢀ87112906; Eꢀmail: cewuwq@scut.edu.cn, jianghf@scut.edu.cn
Abstract: A copperꢀcatalyzed process for the synthesis of substituted quinazolines
from benzonitriles and 2ꢀethynylanilines using molecular oxygen (O2) as sole oxidant
is described. The mild catalytic system enabled the effective cleavage of the CꢀC
triple bond and construction of new C−N, C−C bonds in one operation. Furthermore,
the compound N,Nꢀdimethylꢀ4ꢀ(2ꢀ(4ꢀ(trifluoromethyl)phenyl)quinazolinꢀ4ꢀyl)aniline
(3dj) exhibited obvious aggregationꢀinduced emission (AIE) phenomenon, and the
fluorescence quantum yield (ΦF,film) and lifetime (τfilm) were measured to be 45.5%
and 5.8 ns in thin films state, respectively.
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INTRODUCTION
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Transition metalꢀcatalyzed carbonꢀcarbon bond cleavage has been recognized as a
challenging and attractive area, which provides a new chemical reaction model for
organic synthesis.1 Over the past several decades, much progress has been achieved in
the cleavage of carbonꢀcarbon single bonds and carbonꢀcarbon double bonds.2,3
However, only a few examples on carbonꢀcarbon triple bond cleavage reactions have
been reported, which is due to its extraordinarily large bond dissociation energy (>200
kcal/mol) required.2a In order to achieve this goal,2a,3a,3d many noble metal catalysts
and stoichiometric amount of nonrenewable oxidants are often employed to activate
carbonꢀcarbon triple bond, thereby making their application less desirable. Thus, there
is still room for broadening the scope of more environmentally friendly and more
economic “green” methods to activate carbonꢀcarbon triple bond.
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Scheme 1. Transformations of 2-Alkynylanilines and Indoles
N-Heterocyclic compounds play an important role in organic synthesis because of
their abundance in numerous natural products, biologically active compounds and
materials.4 2ꢀAlkynylanilines as highly versatile building blocks has proven wide
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application in the construction of Nꢀheterocyclic compounds.5 In the past decades,
transitionꢀmetalꢀcatalyzed intramolecular cyclization of 2ꢀethynylanilines have
attracted great attention as one of the efficient strategies to assemble substituted
indoles.6ꢀ14 Most of these strategies involved the intramolecular aminometalation to
afford 3ꢀindolyꢀmetal species, which is trapped with suitable electrophiles or
oxidative coupling with nucleophiles (Scheme 1a). Although much progress has been
achieved in this area, the exploration of novel catalytic system to enrich the diversity
of the transformation remains an active research field.
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Recently, Song and Wang’s group developed the palladiumꢀcatalyzed addition of
indoles with nitriles through 3ꢀindolyꢀpalladium intermediates. which provides a valid
path to 3ꢀacylindoles (Scheme 1b).15 Nevertheless, the nitrogen atoms of nitriles have
not been effectively utilized owing to the hydrolysis of ketimine intermediates. Based
on our continuous interest in the effective transformation of nitriles,16 we describe a
copperꢀcatalyzed synthesis of substituted quinazolines17 from benzonitriles and
2ꢀethynylanilines via carbonꢀcarbon triple bond cleavage using molecular oxygen (O2)
as sole oxidant. This strategy enables effective assembly of quinazolines by CꢀN, CꢀC
bond formations and aerobic CꢀC triple bond cleavage (Scheme 1c).
RESULTS AND DISCUSSION
In preliminary experiments, 2ꢀ(phenylethynyl)aniline (1a, 0.2 mmol) was treated with
Cu(OAc)2 (10 mol %), tꢀBuOK (3 equiv), and benzonitrile (2a, 0.3 mmol) in DMSO
o
(2 mL) under 1 atm O2 atmosphere at 120 C for 24 h, and the desired product
2,4ꢀdiphenylquinazoline (3aa) was observed in 62% yield (Table 1, entry 1). Then, a
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series of copper catalysts were screened and did not display better catalytic activity
than Cu(OAc)2 (Table 1, entries 2ꢀ5). The examination of bases revealed that tꢀBuOK
was the most suitable base for this reaction system (Table 1, entries 6ꢀ12). Other bases
presumably are not conducive to the formation of intermediate A (see Scheme 4), and
the intramolecular cyclization product 2ꢀphenylꢀ1Hꢀindole was obtained in these
cases. However, the use of DMA, DMF, dioxane, toluene or acetonitrile as solvent
was proven to be disadvantageous to the reaction, as the yields were significantly
decreased (Table 1, entries 13ꢀ17). Surprisingly, the reaction of
2ꢀ(phenylethynyl)aniline (1a) with benzonitrile (2a) gave the 2ꢀphenylquinazoline
product (4aa) in 67% yield when toluene was used as the solvent. Reducing the
amount of solvent to 0.5 mL resulted in a higher yield (Table 1, entries 1 vs. 18).
Notably, when the initial substrate ratio was changed, the yield of 3aa enhanced from
81% to 87% (Table 1, entries 18 vs. 19). It is remarkable that the yield decreased
significantly by using anhydrous DMSO as the solvent (Table 1, entry 20). The
importance of H2O was further proven by adding H2O (5.0 equiv) to anhydrous
DMSO, which gave an improved yield of 3aa (Table 1, entries 20 vs. 21). Hence, 1a
(0.2 mmol), 2a (0.4 mmol), Cu(OAc)2 (10 mol %), tꢀBuOK (3 equiv) in DMSO (0.5
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o
mL) under 1 atm O2 atmosphere at 120 C for 24 h were chosen as the optimized
conditions.
Table 1. Optimization of Reaction Conditionsa
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Entry
Catalyst
Cu(OAc)2
Cu(OTf)2
CuSCN
Base
Solvent
DMSO
DMSO
DMSO
DMSO
Yield 3aa/4aa (%)b
62/0
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tꢀBuOK
tꢀBuOK
tꢀBuOK
tꢀBuOK
trace/0
trace/0
trace/0
trace/0
0/0
CuCl2
5
CuBr2
tꢀBuOK
K2CO3
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMA
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6
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
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0/0
Cs2CO3
NaCO3
Ag2CO3
NEt3
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0/0
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0/0
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15c
16c
17c
18d
19e
20e,f
21e,g
0/0
tꢀBuONa
tꢀBuOLi
tꢀBuOK
tꢀBuOK
tꢀBuOK
tꢀBuOK
tꢀBuOK
tꢀBuOK
tꢀBuOK
tꢀBuOK
tꢀBuOK
trace/0
trace/0
24/0
DMF
27/0
dioxane
toluene
acetonitrile
DMSO
DMSO
DMSO
DMSO
0/0
19/67
0/0
81/0
87/0
51/0
84/0
aAll reactions were carried out under the following conditions: 1a (0.2 mmol), 2a (0.3 mmol),
catalyst (10 mol %), base (3 equiv), solvents (2 mL), 120 oC, 24 h, with an O2 balloon. bGC yield
using dodecane as internal standard. Yields determined by GC based on 1a with nꢀdodecane as
internal standard. c100 oC. dSolvents (0.5 mL). e1a (0.2 mmol), 2a (0.4 mmol), solvents (0.5 mL).
fAnhydrous DMSO with 100 mg of 4 Å MS. gAnhydrous DMSO with addition of H2O (5.0 equiv).
To explore the scope and limitations of this approach, various aryl substituted
nitriles 2bꢀ2o were applied to the reaction with 2ꢀ(phenylethynyl)aniline (1a) under
the optimized conditions. Typical results are shown in Table 2. To our delight, most of
the reactions proceeded smoothly to afford the corresponding quinazoline products in
moderate to good yields (3aaꢀ3am). The crystallization of compound 3aa from
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anhydrous ethanol gave single crystals suitable for Xꢀray analysis. The benzonitriles
2bꢀ2f possessing electronꢀdonating group, such as 4ꢀmethyl, 2ꢀmethyl, 4ꢀisopropyl,
4ꢀmethoxy and 1,3ꢀmethylenedioxy at the aryl ring could transfer to the desired
products 3abꢀ3af in 41%ꢀ62% yields, and some substrates bearing an
electronꢀwithdrawing group, including 4ꢀchloro, 2ꢀchloro, 4ꢀbromo and
4ꢀtrifluoromethyl at the benzene ring also reacted smoothly and afforded the desired
products 3agꢀ3aj in 67ꢀ88% yields. Obviously, the electronꢀdeficient aryl substituted
nitriles performed better than the electronꢀrich aryl substituted ones. This might be
due to the electronꢀrich benzonitriles are unfavorable for the nucleophilic addition of
the amino group (see the proposed mechanism in Scheme 4). Sterically hindered
substrates such as 1ꢀ and 2ꢀnaphthonitrile also transformed to the expected products
3al and 3ak in 64% and 51% yields. Furthermore, nitriles bearing a heterocyclic
substituent such as 2ꢀfuronitrile and 2ꢀthiophene could also convert to the desired
products 3am and 3bp in moderate yields. In addition, the transformation of
2ꢀ(phenylethynyl)aniline (1b) possessing an electronꢀwithdrawing group at the aryl
ring (R2 = 4ꢀClC6H4) afforded the desired products 3bn and 3bo in 57% and 56%
yields. The transformations of substrates 1c and 1d possessing an electronꢀdonating
group (R2 = 4ꢀMeC6H4 and R2 = 4ꢀ(dimethylamino)ꢀC6H4) at the benzene ring also
gave the corresponding products 3cm and 3dj in 41% and 46% yields. The
intramolecular cyclization side product 2ꢀphenylꢀ1Hꢀindoles 5c and 5d were detected
in 45% and 39% GC yields in these cases. The electronꢀdonating
5ꢀmethoxyꢀsubstituted (1j) and the electronꢀwithdrawing 4ꢀchloroꢀsubstituted (1k)
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2ꢀethynylanilines were both reacted with 2a under the optimal conditions to provide
3ja and 3ka in 57% and 49% yields.
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Table 2. Synthesis of Substituted Quinazolines 3a,b
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aAll reactions were carried out under the following conditions: 1 (0.2 mmol), 2 (0.4 mmol),
Cu(OAc)2 (10 mol %), tꢀBuOK (3 equiv) and DMSO (0.5 mL), 120 oC, 24 h with an O2 balloon.
bIsolated yields.
Next, we investigated the effects of different 2ꢀ(phenylethynyl)anilines on the
synthesis of 2ꢀphenylquinazoline (4aa) (Scheme 2). Further research showed that the
2ꢀ(phenylethynyl)anilines bearing an electronꢀdonating substituent (1e and 1f)
produced a higher yield of product 4aa than those analogues bearing an
electronꢀwithdrawing substituent (1b and 1f). No desired product was detected when
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heterocyclicꢀsubstituted alkyne was used (1g).
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Scheme 2. Screening for the Alkynesa,b
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aReaction conditions: 1 (0.2 mmol), 2a (0.3 mmol), Cu(OAc)2 (10 mol %), tꢀBuOK (3.0 equiv),
o
b
toluene (0.5 mL), 100 C, 12 h, with an O2 balloon. GC yield using nꢀdodecane as internal
standard. Yields determined by GC based on 1 with nꢀdodecane as internal standard. Isolated yield
is in the parentheses.
Later, we turned our attention to the scope of this transformation. The scope of
aromatic nitriles and substituted 2ꢀalkynylanilines were investigated under the optimal
conditions (Table 3). It was found that benzonitriles with various functional groups
were successfully transformed to the desired 2ꢀ(phenylethynyl)anilines in moderate to
good yields (4ebꢀ4in). In general, the reaction yield was comparatively higher when
electronꢀwithdrawing group (i.e.−F, −Cl, −Br and −CF3) was present on the benzene
ring. This result could be explained by electronꢀdeficient benzonitriles benefit from
the nucleophilic addition of the amino group. Furthermore, nitriles bearing a
heterocyclic substituent such as 2ꢀfuronitrile also gave the desired product in 54%
yield (4em), and amides were found as side products in these reactions.
Table 3. Synthesis of Substituted Quinazolines 4a,b
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O
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Cu(OAc)2 (10 mol %)
t-BuOK (3 equiv)
N
R1
+
N
R3
R1
toluene (0.5 mL)
100 oC, 12 h
O2 balloon
N
NH2
R3
2
4
1
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N
N
N
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N
N
N
Cl
F
4eg, 82%
4eq, 79%
4eb, 71%
N
N
N
N
N
N
O
F
F
Br
4ei, 72%
4ej, 87%
F
4em 54%
N
N
N
N
N
Br
N
F
F
F
4hn, 72%
4hj, 76%
4in, 69%
aAll reactions were carried out under the following conditions: 1 (0.2 mmol), 2 (0.3 mmol),
Cu(OAc)2 (10 mol %), tꢀBuOK (3 equiv) and toluene (0.5 mL), 100 oC, 12 h, with an O2 balloon.
bIsolated yields.
A series of control experiments were subsequently carried out to develop a
deeper understanding of the reaction mechanism (Scheme 3). We conducted the
radical scavengers such as TEMPO (2,2,6,6ꢀtetramethylꢀ1ꢀpiperidinyloxy) or BHT
(3,5ꢀdiꢀtertꢀbutylꢀ4ꢀhydroxytoluene) to the reaction system (Scheme 3a). In both cases,
the formation of 3aa was affected dramatically on the whole. The reaction of
2ꢀ(phenylethynyl)aniline (1a) with benzonitrile (2a) was carried out under a nitrogen
atmosphere, and the corresponding 2,4ꢀdiphenylquinazoline (3aa) was not obtained,
with 2ꢀphenylꢀ1Hꢀindole (5a) as the major product (Scheme 3b), which indicated that
the reaction required the presence of oxygen. The compound 1a was subjected to the
optimized reaction conditions in DMSO and gave 6a and 5a in 67% and 27% yields,
respectively. When toluene was used as the solvent in the reaction, the product 6a was
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formed in 92% yield (Scheme 3c). When 6a was treated with 2a, the desired product
3aa was obtained in 92% yield (Scheme 3d), which suggested that 6a should be the
possible intermediate under the standard reaction conditions. Additionally, when 5a
was subjected to the optimized reaction conditions, 6a could be isolated in 51% yield
(Scheme 3e). However, the reaction of 5a and 2a was conducted under the standard
conditions, only trace amount of products 6a and 3aa could be detected (Scheme 3f),
and 5a presumably is not conducive to the formation of intermediate A due to the
coordination of copper and nitrile (see Scheme 4). These results demonstrated that 5a
might not be the intermediate in the current reaction system.
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Scheme 3. Control Experiments
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On the basis of the above results and previous reports,18 we proposed a plausible
reaction mechanism for this transformation detailed in Scheme 4. This transformation
pathway is initiated by aminocupration of 2ꢀalkynyl aniline to afford the
organocopper(II) intermediate A, which would be further oxidized to intermediate B
in the presence of oxygen. Then, the intramolecular nucleophilic addition of peroxy
anion to the CꢀN double bond forms a fourꢀmembered ring C. Cracking of the peroxy
bond gives the intermediate D, which undergoes the [1,3]ꢀH shift and protonated to
form the intermediate E ([M+Na]+= 348.0683). Subsequently, intermediate F is
formed by CꢀN bond cleavage. In path I, intermediate F with OHꢀ adduct affords
intermediate G, which undergoes rearrangement/decarboxylation to yield intermediate
I, followed by collapse to release 6a. Finally, the condensation of 6a with benzonitrile
2a gives 3aa. When toluene is used as solvent (path II), the nitrile group can be
readily activated through the coordination with the potassium cation in the presence of
tꢀBuOK.18d The addition of the amino group of F to nitrile group generates the
intermediate J. Then the intramolecular cyclization of J affords K ([M+Na]+=
333.0996), which quickly converts into intermediate L by OHꢀ addition. Eventually, L
undergoes cleavage to yield hydroxide ion, benzoic acid ([M+Na]+= 145.0258 ), and
4aa.18e,18f
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Scheme 4. Possible Reaction Mechanism
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Interestingly, only 3dj of all the products shows bright emission in the solid state,
when excited under an ultraviolet lamp (365 nm), and the fluorescence quantum yield
(ΦF,film) and lifetime (τfilm) were measured to be 45.5% and 5.8 ns in thin films state,
respectively. Furthermore, the fluorescence spectra of 3dj exhibited obvious
wavelength changes in different solvents, which showed that the Stokes shift
increased quickly on increasing the solvent polarity (Figures 1a and 1b). In order to
evaluate the optical properties of product 3dj, the PL spectra of 3dj in the THF/water
mixtures with various water content was then investigated (Figure 1c). In pure THF
solution, 3dj exhibits bright green luminescence, however, the photoluminescence
intensity showed nearly sustained decrease until the water fraction (fw) reached 70%,
and the 41nm red shift could also be detected. This phenomenon could be attributed to
an increase in the solvent polarity and intramolecular chargeꢀtransfer (ICT)
mechanism. From 73% fw to 90% fw, the PL intensity of 3dj gradually increased,
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demonstrating the aggregation induced emission (AIE) effect. In this stage, because
increasing the water content would reduce the solubility, 3dj began to aggregate.
Meanwhile, the ICT effect was efficiently weakened. The fluorescence intensity of
3dj in water/THF mixture (fw = 90%) buffered by BR under different pH conditions
was also determined (Figure 1d). A weak fluorescence intensity was seen at pH 1.
With the gradually increase of the pH from 2 to 5, enhanced fluorescence intensity
was observed. When adjusted the pH of the solution from 6 to 12, the emission
behavior was similar, indicating that no state change at the range pH values, and the
fluorescence intensity at 482 nm was plotted at different pH values (on the Figure 1d).
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Figure 1. (a) Excitation spectra of 3dj in different solvents. (b) Emission spectra of 3dj in
different solvents. (c) Fluorescence spectra of 3dj in THF/water mixtures (10ꢀ5 mol/L). (d)
Fluorescence spectra of 3dj in solutions (10ꢀ5 mol /L) of different pH.
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CONCLUSION
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In conclusion, we have developed a concise construction of substituted quinazoline
derivatives via Cu(OAc)2ꢀcatalyzed cyclization of 2ꢀethynylanilines with
benzonitriles. The process produced substituted quinazolines in moderate to good
yields with readily available staring materials and catalyst. With this powerful
synthetic strategy, we discovered a new solidꢀstate blueꢀemitting organic molecule.
This method provided a clue about the further development of new types of
aggregation induced emission (AIE) luminescent materials.
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EXPERIMENTAL SECTION
General Information: NMR spectra were obtained using a Bruker Avance 400
1
spectrometer (1H at 400 MHz, and 13 C at 101 MHz). Chemical shifts for H NMR
spectra are reported in parts per million (ppm) from tetramethylsilane with the solvent
resonance as the internal standard (CDCl3: δ 7.26 ppm). Chemical shifts for 13C NMR
spectra are reported in parts per million (ppm) from tetramethylsilane with the solvent
as the internal standard (CDCl3: δ 77.0 ppm). IR spectra were obtained either as
potassium bromide pellets or as liquid films between two potassium bromide pellets
with a spectrometer. GC−MS was obtained using electron ionization. HRMS was
obtained with a LCMSꢀITꢀTOF mass spectrometer. UVꢀvis absorption spectra were
obtained using Shimadzu UVꢀ2600 spectrophotometer. Photoluminescence spectra
were recorded on a Horiba Fluoromaxꢀ4 spectrofluorometer. Thin film fluorescence
quantum yields were measured using a Hamamatsu absolute PL quantum yield
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spectrometer C11347 QuantaurusꢀQY. Fluorescence lifetimes were determined with a
Hamamatsu C11367ꢀ11 QuantaurusꢀTau timeꢀresolved spectrometer.
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General Procedure for the Preparation of Compound 3: The reaction mixture of
2ꢀethynylanilines 1 (0.2 mmol), nitriles 2 (0.4 mmol), Cu(OAc)2 (10 mol %) and
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o
tꢀBuOK (3 equiv) were added to DMSO (0.5 mL). The mixture was stirred at 120 C
for 24 h under O2 balloon and monitored periodically by TLC. Upon completion, the
reaction mixture was diluted with water (30 mL) and extracted with ethyl acetate (3 ×
30 mL). The combined organic layers were washed with water and brine, dried over
Na2SO4 and filtered. The solvent was removed under vacuum. The residue was
purified by flash column chromatography to afford substituted quinazolines 3.
General Procedure for the Preparation of Compound 4: The reaction mixture of
oꢀalkynylanilines 1 (0.2 mmol), nitriles 2 (0.4 mmol), Cu(OAc)2 (10 mol %) and
tꢀBuOK (3 equiv) were added to toluene (0.5 mL). The mixture was stirred at 100 oC
for 12 h under O2 balloon, and monitored periodically by TLC. Upon completion, the
reaction mixture was diluted with water (30 mL) and extracted with ethyl acetate (3 ×
30 mL). The combined organic layers were washed with water and brine, dried over
Na2SO4 and filtered. The solvent was removed under vacuum. The residue was
purified by flash column chromatography to afford substituted quinazolines 4.
2,4-Diphenylquinazoline (3aa)19: Purified via flash column chromatography with
40% ethyl acetate/petroleum ether, yielding 81% (45.7 mg) as a white solid: 117ꢀ119
oC. H NMR (400 MHz, CDCl3, δ ppm) 8.73 (d, J = 7.3 Hz, 2H), 8.15 (dd, J = 17.4,
1
8.4 Hz, 2H), 7.89ꢀ7.86 (m, 3H), 7.61ꢀ7.53 (m, 7H); 13C NMR (101 MHz, CDCl3, δ
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ppm) 168.3, 160.2, 151.9, 138.2, 137.6, 133.5, 130.5, 130.1, 129.9, 129.1, 128.6,
128.5, 126.9, 121.6. IR (KBr, cm–1): 2921, 1538, 1477, 1326, 754. HRMS (ESI) m/z:
calcd for C20H15N2 [M + H]+ 283.1230; found 283.1238.
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4-Phenyl-2-(p-tolyl)quinazoline
(3ab)22:
Purified
via
flash
column
chromatography with 40% ethyl acetate/petroleum ether, yielding 61% (36 mg) as a
o
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white solid: 166ꢀ168 C. H NMR (400 MHz, CDCl3, δ ppm) δ 8.60 (d, J = 8.1 Hz,
2H), 8.15ꢀ8.10 (m, 2H), 7.95ꢀ7.84 (m, 3H), 7.66ꢀ7.57 (m, 3H), 7.55ꢀ7.40 (m, 1H),
7.34 (d, J = 8.0 Hz, 2H), 2.45 (s, 3H), 13C NMR (101 MHz, CDCl3, δ ppm) δ 168.3,
160.3, 151.9, 140.8, 137.8, 135.5, 133.5, 130.2, 129.9, 129.3, 129.0, 128.7,128.5,
127.0, 126.8, 121.6, 21.5. IR (KBr, cm–1): 2919, 1533, 1456, 1334, 764. HRMS (ESI)
m/z: calcd for C21H17N2 [M + H]+ 297.1386; found 297.1387.
4-Phenyl-2-(o-tolyl)quinazoline
(3ac)22:
Purified
via
flash
column
chromatography with 40% ethyl acetate/petroleum ether, yielding 57% (33.7 mg) as a
white solid: 72ꢀ74 oC. 1H NMR (400 MHz, CDCl3, δ ppm) 8.18 (dd, J = 8.2, 5.0 Hz,
2H), 8.03ꢀ7.97 (m, 1H), 7.95ꢀ7.83 (m, 3H), 7.6ꢀ7.55 (m, 4H), 7.38ꢀ7.31 (m, 3H), 2.69
(s, 3H), 13C NMR (101 MHz, CDCl3, δ ppm) 168.1, 163.4, 151,7, 138.8, 137.5, 137.4,
133.6, 131.3, 130.8, 130.2, 130.0, 129.2, 129.0, 128.6, 127.3, 127.0, 126.0, 121.0,
21.3. IR (KBr, cm–1): 2919, 1537, 1462, 1259, 1087, 799. HRMS (ESI) m/z: calcd for
C21H17N2 [M + H]+ 297.1386; found 297.1382.
2-(4-Isopropylphenyl)-4-phenylquinazoline (3ad): Purified via flash column
chromatography with 40% ethyl acetate/petroleum ether, yielding 59% (38.2 mg) as a
o
1
white solid: 92ꢀ94 C. H NMR (400 MHz, CDCl3, δ ppm) 8.65 (d, J = 8.3 Hz, 2H),
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8.17ꢀ8.10 (m, 2H), 7.92ꢀ7.84 (m, 3H), 7.62ꢀ7.58 (m, 3H), 7.54ꢀ7.49 (m, 1H), 7.42 (d,
J = 8.3 Hz, 2H), 3.02 (septet, J = 7.5, 6.9 Hz, 1H), 1.34 (s, 3H), 1.32 (s, 3H), 13C
NMR (101 MHz, CDCl3, δ ppm) 168.1, 160.3, 151.9, 151.5, 137.7, 135.9, 133.4,
130.1, 129.8, 129.0, 128.7, 128.4, 126.9, 126.7, 126.6, 121.5, 34.1, 23.8. IR (KBr,
cm–1): 2960, 1536, 1453, 1339, 1261, 770. HRMS (ESI) m/z: calcd for C23H21N2 [M
+ H]+ 325.1699; found 325.1697.
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2-(4-Methoxyphenyl)-4-phenylquinazoline (3ae)19: Purified via flash column
chromatography with 40% ethyl acetate/petroleum ether, yielding 41% (25.6 mg) as a
white solid: 158ꢀ160 oC. 1H NMR (400 MHz, CDCl3, δ ppm) 8.66 (d, J = 8.8 Hz, 2H),
8.11 (t, J = 8.6 Hz, 2H), 7.93ꢀ 7.82 (m, 3H), 7.66ꢀ7.55 (m, 3H), 7.51 (t, J = 7.6 Hz,
1H), 7.04 (d, J = 8.8 Hz, 2H), 3.90 (s, 3H); 13C NMR (101 MHz, CDCl3, δ ppm)
δ168.2, 161.8, 160.1, 152.1, 137.8, 133.5, 131.0, 130.0, 129.9, 128.9, 128.5, 127.0,
126.5, 121.4, 113.9, 55.4. IR (KBr, cm–1): 2920, 1533, 1461, 1337, 1251, 765. HRMS
(ESI) m/z: calcd for C21H17N2O [M + H]+ 313.1335; found 313.1342.
2-(Benzo[d][1,3]dioxol-5-yl)-4-phenylquinazoline (3af)21: Purified via flash
column chromatography with 40% ethyl acetate/petroleum ether, yielding 62% (40.4
o
1
mg) as a white solid: 169ꢀ170 C. H NMR (400 MHz, CDCl3, δ ppm) 8.32 (dd, J =
8.2, 1.6 Hz, 1H), 8.20 (d, J = 1.6 Hz, 1H), 8.09 (dd, J = 8.6, 2.8 Hz, 2H), 7.88ꢀ7.85 (m,
3H), 7.63ꢀ7.56 (m, 3H), 7.50 (ddd, J = 8.2, 7.0, 1.0 Hz, 1H), 6.95 (d, J = 8.2 Hz, 1H),
13
6.04 (s, 2H), C NMR (101 MHz, CDCl3, δ ppm) 168.1, 159.7, 152.0, 149.8, 148.1,
137.7, 133.5, 132.7, 130.2, 129.9, 129.0, 128.5, 127.0, 126.7, 123.6, 121.5, 108.9,
108.3, 101.4. IR (KBr, cm–1): 2921, 1536, 1495, 1333, 774. HRMS (ESI) m/z: calcd
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for C21H15N2O2 [M + H]+ 327.1128; found 327.1127.
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2-(4-Chlorophenyl)-4-phenylquinazoline (3ag)22: Purified via flash column
chromatography with 40% ethyl acetate/petroleum ether, yielding 84% (53 mg) as a
white solid: 190ꢀ192 oC. 1H NMR (400 MHz, CDCl3, δ ppm) 8.65 (d, J = 7.9 Hz, 2H),
8.14 (t, J = 7.5 Hz, 2H), 7.94ꢀ7.84 (m, 3H), 7.60ꢀ7.56 (m, 4H), 7.49 (d, J = 7.9 Hz,
2H), 13C NMR (101 MHz, CDCl3, δ ppm) 168.5, 159.3, 151.9, 137.5, 136.8, 136.7,
133.7, 130.1, 130.0, 129.1, 128.7, 128.5, 127.2, 127.0, 121.7. IR (KBr, cm–1 ): 2918,
1533, 1471, 1332, 1159, 1084. HRMS (ESI) m/z: calcd for C20H14ClN2 [M + H]+
317.0840; found 317.0843.
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2-(2-Chlorophenyl)-4-phenylquinazoline (3ah)22: Purified via flash column
chromatography with 40% ethyl acetate/petroleum ether, yielding 67% (42.3 mg) as a
o
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white solid: 93ꢀ95 C. H NMR (400 MHz, CDCl3, δ ppm) 8.19 (t, J = 7.5 Hz, 2H),
7.97ꢀ7.84 (m, 4H), 7.63ꢀ7.52 (m, 5H), 7.42ꢀ7.38 (m, 2H); 13C NMR (101 MHz,
CDCl3, δ ppm) 168.1, 161.2, 151.4, 138.4, 137.1, 133.7, 132.9, 131.7, 130.4, 130.1,
130.0, 129.0, 128.9, 128.5, 127.9, 127.7, 126.9, 121.2. IR (KBr, cm–1): 2920, 1535,
1481, 1335, 757. HRMS (ESI) m/z: calcd for C20H13ClN2Na [M + Na]+ 339.0659;
found 339.0653.
2-(4-Bromophenyl)-4-phenylquinazoline (3ai)20: Purified via flash column
chromatography with 40% ethyl acetate/petroleum ether, yielding 87% (62.6 mg) as a
white solid: 192ꢀ194 oC. 1H NMR (400 MHz, CDCl3, δ ppm) 8.62ꢀ8.55 (m, 2H), 8.13
(dd, J = 12.2, 4.6 Hz, 2H), 7.93ꢀ7.84 (m, 3H), 7.67ꢀ7.54 (m, 6H), 13C NMR (101
MHz, CDCl3, δ ppm) 168.5, 159.3, 151.9, 137.5, 137.1, 133.7, 131.7, 130.2, 130.1,
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130.0, 129.1, 128.6, 127.2, 127.0, 125.3, 121.7. IR (KBr, cm–1): 2920, 1534, 1459,
1386, 694. HRMS (ESI) m/z: calcd for C20H14BrN2 [M + H]+ 361.0335; found
361.0331.
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4-Phenyl-2-(4-(trifluoromethyl)phenyl)quinazoline (3aj)20: Purified via flash
column chromatography with 40% ethyl acetate/petroleum ether, yielding 88% (63
o
1
mg) as a white solid: 124ꢀ126 C. H NMR (400 MHz, CDCl3, δ ppm) 8.82 (d, J =
8.1 Hz, 2H), 8.15 (t, J = 8.7 Hz, 2H), 7.89 (dd, J = 8.9, 5.1 Hz, 3H), 7.78 (d, J = 8.2
Hz, 2H), 7.65 ꢀ7.54 (m, 4H), 13C NMR (101 MHz, CDCl3, δ ppm) 168.5, 158.8,
151.9, 141.6, 137.5, 133.8, 132.1(q, J = 270.8 Hz), 130.2, 130.1, 129.3, 128.9, 128.6,
127.6, 127.1, 125.4 (q, J = 3.8 Hz), 124.0 (q, J = 270.8 Hz), 122.0, 19F NMR (376
MHz, CDCl3, δ ppm) ꢀ62.57. IR (KBr, cm–1): 2924, 1539, 1485, 1319, 1107, 769.
HRMS (ESI) m/z: calcd for C21H14F3N2 [M + H]+ 351.1104; found 351.1110.
2-(Naphthalen-2-yl)-4-phenylquinazoline (3ak)19: Purified via flash column
chromatography with 40% ethyl acetate/petroleum ether, yielding 51% (33.9 mg) as a
white solid: 182ꢀ184 oC. 1H NMR (400 MHz, CDCl3, δ ppm) 9.26 (s, 1H), 8.83 (dd, J
= 8.6, 1.3 Hz, 1H), 8.23 (d, J = 8.4 Hz, 1H), 8.15 (d, J = 8.3 Hz, 1H), 8.08ꢀ 8.03 (m,
1H), 8.00 (d, J = 8.7 Hz, 1H), 7.98ꢀ7.86 (m, 4H), 7.67ꢀ7.49 (m, 6H), 13C NMR (101
MHz, CDCl3, δ ppm) 168.5, 160.2, 152.0, 137.7, 135.5, 134.7, 133.7, 133.5, 130.3,
130.0, 129.4, 129.1, 129.0, 128.6, 128.2, 127.7, 127.1, 127.0, 126.1, 125.6, 121.8.
IR (KBr, cm–1): 2921, 1540, 1465, 1332, 698. HRMS (ESI) m/z: calcd for C24H17N2
[M + H]+ 333.1386; found 333.1382.
2-(Naphthalen-1-yl)-4-phenylquinazoline (3al)19: Purified via flash column
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chromatography with 40% ethyl acetate/petroleum ether, yielding 64% (42.5 mg) as a
white solid: 171ꢀ173 oC. 1H NMR (400 MHz, CDCl3, δ ppm) 8.85 (d, J = 8.4 Hz, 1H),
8.27 (ddd, J = 27.1, 12.9, 4.5 Hz, 3H), 8.03ꢀ7.90 (m, 5H), 7.67ꢀ7.52 (m, 7H), 13C
NMR (101 MHz, CDCl3, δ ppm) 168.4, 162.7, 151.7, 137.4, 136.5, 134.2, 133.7,
131.3, 130.1, 130.0, 129.9, 129.6, 129.1, 128.5, 128.4, 127.4, 126.9, 126.7, 126.1,
125.7, 125.3, 121.2. IR (KBr, cm–1): 2920, 1535, 1464, 1325, 768. HRMS (ESI) m/z:
calcd for C24H16N2Na [M + Na]+ 355.1206; found 355.1209.
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2-(Furan-2-yl)-4-phenylquinazoline (3am)19: Purified via flash column
chromatography with 40% ethyl acetate/petroleum ether, yielding 71% (38.6 mg) as a
white solid: 166ꢀ168 oC. 1H NMR (400 MHz, CDCl3, δ ppm) 8.16 (d, J = 8.5 Hz, 1H),
8.05 (d, J = 8.3 Hz, 1H), 7.89ꢀ7.78 (m, 3H), 7.69 (s, 1H), 7.60ꢀ7.55 (m, 3H),
7.53ꢀ7.47 (m, 2H), 6.59 (dd, J = 3.4, 1.7 Hz, 1H); 13C NMR (101 MHz, CDCl3, δ
ppm) 168.8, 153.5, 152.8, 151.6, 145.3, 137.2, 133.9, 130.1, 130.0, 128.9, 128.6,
127.1, 127.0, 121.6, 114.3, 112.2. IR (KBr, cm–1): 2922, 1536, 1481, 1336, 758.
HRMS (ESI) m/z: calcd for C18H12N2NaO [M + Na]+ 295.0842; found 295.0841.
4-(4-Chlorophenyl)-2-(4-ethylphenyl)quinazoline (3bn): Purified via flash
column chromatography with 40% ethyl acetate/petroleum ether, yielding 57% (39.3
o
1
mg) as a white solid: 178ꢀ180 C. H NMR (400 MHz, CDCl3, δ ppm) 8.59 (d, J =
8.2 Hz, 2H), 8.15 (d, J = 8.4 Hz, 1H), 8.06 (d, J = 8.2 Hz, 1H), 7.91ꢀ 7.81 (m, 3H),
7.62ꢀ7.49 (m, 3H), 7.36 (d, J = 8.1 Hz, 2H), 2.75 (q, J = 7.6 Hz, 2H), 1.30 (t, J = 7.6
Hz, 3H), 13C NMR (101 MHz, CDCl3, δ ppm) 167.0, 160.4, 152.1, 147.2, 136.2,
136.1, 135.6, 133.6, 131.5, 129.2, 128.8, 128.7, 128.2, 127.0, 126.6, 121.4, 28.9, 15.5.
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IR (KBr, cm–1): 2922, 1536, 1459, 1333, 759. HRMS (ESI) m/z: calcd for
C22H18ClN2 [M + H]+ 345.1153; found 345.1155.
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column chromatography with 40% ethyl acetate/petroleum ether, yielding 56% (39.1
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mg) as a white solid: 185ꢀ187oC. H NMR (400 MHz, CDCl3, δ ppm) 8.31 (s, 2H),
8.19 (d, J = 8.4 Hz, 1H), 8.08 (d, J = 8.3 Hz, 1H), 7.95ꢀ7.84 (m, 3H), 7.66ꢀ7.52 (m,
3H), 7.18 (s, 1H), 2.48 (s, 6H), 13C NMR (101 MHz, CDCl3, δ ppm) 167.1, 160.6,
152.0, 138.1, 137.9, 136.2, 136.1, 133.7, 132.5, 131.6, 129.3, 128.9, 127.1, 126.5,
126.4, 121.5, 21.5. IR (KBr, cm–1): 2921, 1540, 1479, 1340, 757. HRMS (ESI) m/z:
calcd for C22H18ClN2 [M + H]+ 345.1153; found 345.1152.
4-(4-Chlorophenyl)-2-(thiophen-2-yl)quinazoline (3bp): Purified via flash
column chromatography with 40% ethyl acetate/petroleum ether, yielding 66% (42.5
o
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mg) as a white solid: 157ꢀ159 C. H NMR (400 MHz, CDCl3, δ ppm) 8.19 (d, J =
3.5 Hz, 1H), 8.08 (d, J = 8.5 Hz, 1H), 8.03 (d, J = 8.3 Hz, 1H), 7.87 (t, J = 7.7 Hz,
1H), 7.82 (d, J = 8.4 Hz, 2H), 7.60ꢀ 7.46 (m, 4H), 7.21ꢀ7.15 (m, 1H); 13C NMR (101
MHz, CDCl3, δ ppm) 167.1, 157.2, 151.9, 144.0, 136.4, 135.7, 133.9, 131.5, 130.0,
129.4, 128.9, 128.3, 126.9, 126.7, 121.3. IR (KBr, cm–1): 2921, 1531, 1483, 1338, 711.
HRMS (ESI) m/z: calcd for C18H12N2SCl [M + H]+ 323.0404; found 323.0398.
2-(Furan-2-yl)-4-(p-tolyl)quinazoline (3cm): Purified via flash column
chromatography with 40% ethyl acetate/petroleum ether, yielding 41% (23.5 mg) as a
white solid: 138ꢀ140 oC. 1H NMR (400 MHz, CDCl3, δ ppm) 8.16 (d, J = 8.5 Hz, 1H),
8.09 (d, J = 8.4 Hz, 1H), 7.88ꢀ7.86 (m, 1H), 7.74 (d, J = 8.0 Hz, 2H), 7.69 (s, 1H),
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7.53ꢀ7.49 (m, 2H), 7.39 (d, J = 7.9 Hz, 2H), 6.60ꢀ6.59 (m, 1H), 2.46 (s, 3H); 13C
NMR (101 MHz, CDCl3, δ ppm) 168.9, 153.5, 152.9, 151.6, 145.2, 140.3, 134.4,
133.8, 130.1, 129.3, 128.9, 127.3, 126.9, 121.7, 114.2, 112.2, 21.5. IR (KBr, cm–1 ):
2921, 1534, 1478, 1263, 755. HRMS (ESI) m/z: calcd for C19H14N2NaO [M + Na]+
309.0998; found 309.1003.
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N,N-Dimethyl-4-(2-(4-(trifluoromethyl)phenyl)quinazolin-4-yl)aniline
(3dj):
Purified via flash column chromatography with 40% ethyl acetate/petroleum ether,
o
yielding 46% (36.2 mg) as a white solid: 136ꢀ138 C. 1H NMR (400 MHz, CDCl3, δ
ppm) 8.82 (d, J = 8.2 Hz, 2H), 8.29 (d, J = 8.1 Hz, 1H), 8.12 (d, J = 8.4 Hz, 1H),
7.92ꢀ7.83 (m, 3H), 7.77 (d, J = 8.3 Hz, 2H), 7.56 (t, J = 7.6 Hz, 1H), 6.89 (d, J = 8.8
Hz, 2H), 3.10 (s, 6H), 13C NMR (101 MHz, CDCl3, δ ppm) 168.1, 158.7, 152.0,
151.9, 142.0, 138.8 (q, J = 36.9 Hz), 133.3, 131.9, 129.1, 128.8, 127.5, 127.0, 125.3
(q, J = 3.6 Hz), 124.9, 124.3 (q, J = 270.4 Hz), 121.9, 111.8, 40.3, 19F NMR (376
MHz, CDCl3, δ ppm) ꢀ62.73. IR (KBr, cm–1): 2919, 1643, 1462, 1262, 754. HRMS
(ESI) m/z: calcd for C23H19F3N3 [M + H]+ 394.1526; found 394.1533.
7-Methoxy-2,4-diphenylquinazoline (3ja): Purified via flash column
chromatography with 40% ethyl acetate/petroleum ether, yielding 57% (35.6 mg) as a
white solid: 235ꢀ237 oC. 1H NMR (400 MHz, CDCl3, δ ppm) 8.67 (d, J = 7.3 Hz, 2H),
8.01 (d, J = 9.2 Hz, 1H), 7.87ꢀ7.85 (m, 2H), 7.58ꢀ7.57 (m, 3H), 7.54ꢀ7.47 (m, 4H),
7.16 (d, J = 9.1 Hz, 1H), 4.03 (s, 3H); 13C NMR (101 MHz, CDCl3, δ ppm) 167.3,
163.8, 160.9, 154.4, 138.3, 137.9, 130.5, 130.1, 129.8, 128.7, 128.5, 128.4, 120.3,
117.1, 106.6, 55.8. IR (KBr, cm–1): 2922, 1763, 1693, 1242, 1026, 697. HRMS (ESI)
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m/z: calcd for C21H17ON2 [M + H]+ 313.1335; found 313.1336.
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6-Chloro-2,4-diphenylquinazoline (3ka)19: Purified via flash column
chromatography with 40% ethyl acetate/petroleum ether, yielding 49% (30.9 mg) as a
white solid: 195ꢀ197 oC. 1H NMR (400 MHz, CDCl3, δ ppm) 8.71ꢀ8.66 (m, 2H), 8.14
(d, J = 9.0 Hz, 1H), 8.10 (d, J = 2.1 Hz, 1H), 7.88ꢀ7.81 (m, 3H), 7.65ꢀ7.60 (m, 3H),
7.55ꢀ7.50 (m, 3H); 13C NMR (101 MHz, CDCl3, δ ppm) 167.7, 160.5, 150.4, 137.7,
137.1, 134.6, 132.7, 130.8, 130.7, 130.3, 130.1, 128.7, 128.7, 128.6, 125.8, 122.2. IR
(KBr, cm–1): 2988, 1748, 1244, 1049, 798. HRMS (ESI) m/z: calcd for C20H14ClN2
[M + H]+ 317.0840; found 317.0844.
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2-Phenylquinazoline (4aa)23: Purified via flash column chromatography with 40%
ethyl acetate/petroleum ether, yielding 79% (32.5 mg) as a white solid: 98ꢀ100 oC. 1H
NMR (400 MHz, CDCl3, δ ppm) 9.46 (s, 1H), 8.67ꢀ8.59 (m, 2H), 8.12ꢀ8.06 (m, 1H),
13
7.93ꢀ7.86 (m, 2H), 7.64ꢀ7.51 (m, 4H); C NMR (101 MHz, CDCl3, δ ppm) δ 161.1,
160.5, 150.8, 138.0, 134.1, 130.6, 128.7, 128.6, 127.3, 127.1, 123.6. IR (KBr, cm–1):
2923, 1556, 1455, 1266, 757. HRMS (ESI) m/z: calcd for C14H11N2 [M + H]+
207.0917; found 207.0919.
2-(p-Tolyl)quinazoline (4eb)23: Purified via flash column chromatography with
40% ethyl acetate/petroleum ether, yielding 71% (31.2 mg) as a white solid: 97ꢀ99 oC.
1H NMR (400 MHz, CDCl3, δ ppm) 9.44 (s, 1H), 8.52 (d, J = 8.2 Hz, 2H), 8.13ꢀ8.01
(m, 1H), 7.95ꢀ7.80 (m, 2H), 7.64ꢀ7.50 (m, 1H), 7.34 (d, J = 8.0 Hz, 2H), 2.45 (s, 3H);
13C NMR (101 MHz, CDCl3, δ ppm) 161.2, 160.4, 150.8, 140.9, 135.3, 134.1, 129.4,
128.6, 127.1, 127.0, 123.5, 21.52. IR (KBr, cm–1): 2926, 1559, 1459, 1266, 755.
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HRMS (ESI) m/z: calcd for C15H13N2 [M + H]+ 221.1073; found 221.1079.
2-(4-Fluorophenyl)quinazoline (4eq)23: Purified via flash column chromatography
with 40% ethyl acetate/petroleum ether, yielding 79% (35.4 mg) as a yellow solid:
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136ꢀ137 C. H NMR (400 MHz, CDCl3, δ ppm) 9.45 (s, 1H), 8.68ꢀ 8.58 (m, 2H),
8.07 (d, J = 8.4 Hz, 1H), 7.95ꢀ7.87 (m, 2H), 7.62 (dd, J = 11.0, 4.0 Hz, 1H), 7.24ꢀ7.13
(m, 2H); 13C NMR (101 MHz, CDCl3, δ ppm)165.9, 163.5, 160.5, 160.1, 150.7,
134.3, 134.2, 130.70 (d, J = 8.7 Hz), 128.6, 127.22 (d, J = 14.2 Hz), 123.5, 115.5 (d, J
= 21.5 Hz), 19F NMR (376 MHz, CDCl3, δ ppm) ꢀ110.52. IR (KBr, cm–1): 2921, 1585,
1402, 1219, 800. HRMS (ESI) m/z: calcd for C14H10N2F [M + H]+ 225.0823; found
225.0825.
2-(4-Chlorophenyl)quinazoline
(4eg)23:
Purified
via
flash
column
chromatography with 40% ethyl acetate/petroleum ether, yielding 82% (39.4 mg) as a
yellow solid: 137ꢀ139 oC. 1H NMR (400 MHz, CDCl3, δ ppm) 9.43 (s, 1H), 8.60ꢀ8.51
(m, 2H), 8.09ꢀ8.01 (m, 1H), 7.95ꢀ7.86 (m, 2H), 7.66ꢀ7.57 (m, 1H), 7.53ꢀ7.43 (m, 2H);
13C NMR (101 MHz, CDCl3, δ ppm) 160.5, 160.0, 150.7, 136.9, 136.5, 134.3, 129.9,
128.8, 128.6, 127.5, 127.2, 123.6. IR (KBr, cm–1): 2920, 1575, 1405, 1265, 751.
HRMS (ESI) m/z: calcd for C14H10ClN2 [M + H]+ 241.0527; found 241.0528.
2-(4-Bromophenyl)quinazoline (4ei)23：Purified via flash column chromatography
with 40% ethyl acetate/petroleum ether, yielding 72% (40.7 mg) as a yellow solid:
o
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122ꢀ123 C. H NMR (400 MHz, CDCl3, δ ppm) 9.43 (s, 1H), 8.49 (d, J = 8.5 Hz,
13
2H), 8.06 (d, J = 8.8 Hz, 1H), 7.89 (dd, J = 7.9, 6.3 Hz, 2H), 7.69ꢀ7.56 (m, 3H); C
NMR (101 MHz, CDCl3, δ ppm) 160.4, 160.2, 150.7, 137.0, 134.3, 131.8, 130.2,
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128.6, 127.5, 127.2, 125.4, 123.7. IR (KBr, cm–1): 2991, 1578, 1404, 1265, 752.
HRMS (ESI) m/z: calcd for C14H10N2Br [M + H]+ 285.0022; found 285.0019.
2-(4-(Trifluoromethyl)phenyl)quinazoline (4ej)23: Purified via flash column
chromatography with 40% ethyl acetate/petroleum ether, yielding 87% (47.7 mg) as a
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white solid: 144ꢀ146 C. 1H NMR (400 MHz, CDCl3, δ ppm) 9.47 (s, 1H), 8.74 (d, J
= 8.2 Hz, 2H), 8.10 (d, J = 8.8 Hz, 1H), 7.94 (d, J = 7.6 Hz, 2H), 7.78 (d, J = 8.3 Hz,
2H), 7.68ꢀ7.61 (m, 1H), 13C NMR (101 MHz, CDCl3, δ ppm) 160.6, 159.6, 150.7,
141.3, 134.4, 132.3 (q, J = 32.2 Hz), 128.9, 128.8, 127.9, 127.2, 125.5 (q, J = 3.8 Hz),
123.8, 123.6 (q, J = 292.6 Hz), 19F NMR (376 MHz, CDCl3, δ ppm) ꢀ62.67. IR (KBr,
cm–1): 2923, 1540, 1457, 1262, 756. HRMS (ESI) m/z: calcd for C15H10F3N2 [M +
H]+ 275.0791; found 275.0777.
2-(Furan-2-yl)quinazoline (4em)23: Purified via flash column chromatography
with 40% ethyl acetate/petroleum ether, yielding 54% (21.2 mg) as a white solid:
o
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116ꢀ118 C. H NMR (400 MHz, CDCl3, δ ppm) 9.36 (s, 1H), 8.08 (d, J = 8.8 Hz,
1H), 7.89ꢀ7.85 (m, 2H), 7.68 (d, J = 0.8 Hz, 1H), 7.57 (t, J = 7.5 Hz, 1H), 7.45 (d, J =
3.4 Hz, 1H), 6.60ꢀ6.59 (m, 1H); 13C NMR (101 MHz, CDCl3, δ ppm) δ 160.7, 154.1,
152.5, 150.4, 145.4, 134.5, 128.4, 127.3, 123.4, 114.1, 112.3. IR (KBr, cm–1): 2923,
1587, 1483, 1262, 755. HRMS (ESI) m/z: calcd for C12H8N2NaO [M + Na]+
219.0529; found 219.0526.
7-Methyl-2-(4-(trifluoromethyl)phenyl)quinazoline (4hj): Purified via flash
column chromatography with 40% ethyl acetate/petroleum ether, yielding 76% (43.8
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mg) as a white solid: 157ꢀ159 C. H NMR (400 MHz, CDCl3, δ ppm) 9.37 (s, 1H),
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2.57 (s, 3H); C NMR (101 MHz, CDCl3, δ ppm) 159.9, 158.9, 149.2, 147.0, 141.4,
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270.5 Hz), 122.9, 21.7, F NMR (376 MHz, CDCl3, δ ppm) ꢀ62.66. IR (KBr, cm–1):
2921, 1635, 1415, 1266, 754. HRMS (ESI) m/z: calcd for C16H12F3N2 [M + H]+
289.0947; found 289.0949.
2-(4-Ethylphenyl)-7-methylquinazoline (4hn): Purified via flash column
chromatography with 40% ethyl acetate/petroleum ether, yielding 72% (35.7 mg) as a
white solid: 67ꢀ69oC. H NMR (400 MHz, CDCl3, δ ppm) 9.35 (s, 1H), 8.51 (d, J =
1
8.3 Hz, 2H), 7.97 (d, J = 8.6 Hz, 1H), 7.71ꢀ7.69 (m, 1H), 7.65 (s, 1H), 7.36 (d, J = 8.3
Hz, 2H), 2.74 (q, J = 7.6 Hz, 2H), 2.55 (s, 3H), 1.30 (t, J = 7.6 Hz, 3H); 13C NMR
(101 MHz, CDCl3, δ ppm) 160.6, 159.7, 149.4, 146.9, 137.2, 136.3, 135.7, 128.5,
128.3, 128.1, 125.8, 123.5, 28.9, 21.6, 15.4. IR (KBr, cm–1): 2921, 1562, 1423, 1263,
754. HRMS (ESI) m/z: calcd for C17H17N2 [M + H]+ 249.1386; found 249.1385.
7-Bromo-2-(4-ethylphenyl)quinazoline (4in): Purified via flash column
chromatography with 40% ethyl acetate/petroleum ether, yielding 69% (43 mg) as a
white solid: 143ꢀ145oC. 1H NMR (400 MHz, CDCl3, δ ppm) 9.36 (s, 1H), 8.51 (d, J =
8.0 Hz, 2H), 8.05 (s, 1H), 7.94 (s, 2H), 7.36 (d, J = 7.9 Hz, 2H), 2.77ꢀ2.70 (m, 2H),
1.29 (d, J = 7.6 Hz, 3H); 13C NMR (101 MHz, CDCl3, δ ppm) 161.5, 159.3, 149.5,
147.6, 137.5, 135.1, 130.4, 129.2, 128.7, 128.3, 124.4, 120.5, 28.9, 15.4. IR (KBr,
cm–1): 2921, 1543, 1418, 1263, 753. HRMS (ESI) m/z: calcd for C16H14BrN2 [M +
H]+ 313.0335; found 313.0335.
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ASSOCIATED CONTENT
Supporting Information
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Copies of NMR spectra for all compounds and Xꢀray crystallographic data for 3aa.
This material is available free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
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Corresponding Authors
cewuwq@scut.edu.cn; jianghf@scut.edu.cn
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENT
The authors thank the National Program on Key Research Project (2016YFA0602900),
the National Natural Science Foundation of China (21490572 and 21420102003), and
Pearl River S&T Nova Program of Guangzhou (201610010160) for financial support.
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