One-pot regioselective C-H activation iodination-cyanation of 2,4-diarylquinazolines using malononitrile as a cyano source

Article abstract of DOI:10.1039/c9ra02979f

A one-pot cyanation of 2,4-arylquinazoline with NIS and malononitrile has been developed. The one-pot reaction includes two steps. The Rh-catalyzed selective C-H activation/iodization of 2,4-diarylquinazoline with NIS, and then Cu-catalyzed cyanation of t

Full text of DOI:10.1039/c9ra02979f

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One-pot regioselective C–H activation iodination–
cyanation of 2,4-diarylquinazolines using
malononitrile as a cyano source†
Cite this: RSC Adv., 2019, 9, 18256
a
b
a
a
a
Ziqiao Yan, Banlai Ouyang, Xunchun Mao, Wei Gao, Zhihong Deng
a
and Yiyuan Peng
*
A one-pot cyanation of 2,4-arylquinazoline with NIS and malononitrile has been developed. The one-pot
reaction includes two steps. The Rh-catalyzed selective C–H activation/iodization of 2,4-
diarylquinazoline with NIS, and then Cu-catalyzed cyanation of the corresponding iodinated intermediate
with malononitrile to selectively give 2-(2-cyanoaryl)-4-arylquinazolines or 2-(2,6-dicyanoaryl)-4-
arylquinazolines in good to excellent yields.
Received 21st April 2019
Accepted 28th May 2019
DOI: 10.1039/c9ra02979f
rsc.li/rsc-advances
Although attempts have been made to utilize malononitrile as
the cyano-group source in several aryl halogens cyanation
Aromatic nitriles have broad applications in agrochemicals, reactions (Scheme 1a), there is no report about utilizing it as
pharmaceuticals and materials science. The nitrile moiety also
Introduction
23
serves as a pivotal precursor for a multitude of conversions into
a great number of other functional groups, such as hydrolysis
into carboxyl or amide, reduction into aldehydes or amines,
1
cycloaddition into heterocycles, etc. Consequently, a number of
methods have been developed to introduce a cyanogen group to
an aromatic ring. Various catalytic systems and cyanating
agents have been established. Of these transformations,
2a
transition-metal-catalyzed cyanation of aryl halides
or
aromatic C–H bond activation/cyanation was an elegant route to
2
b
3
4
5
6
arylnitriles. Cu(CN) , Zn(CN) , NaCN and KCN, CuSCN,
2
2
7
8
9
10
cyanogen halides, TMSCN, NaN
3
, and K
4
[Fe(CN)
6
]
have been
used as cyanation agents to introduce CN into organic mole-
cules. Organic cyanide sources and their combined cyano-
1
1
12
groups, such as CH
3
NO
2
,
acetone cyanohydrin, N-cyano-N-
13
phenyl-p-toluenesulfonamide (NCTS),
aryl(cyano)iodonium
14
15
16
16f,16g
triates, amine/DMSO, DMF, formamide,
ethyl cya-
17
18
noacetate,
ethyl(ethoxymethylene)cyanoacetate, benzyl
cyanide, tert-butyl nitrite (TBN), isocyanides, and acetoni-
trile have been used in cyanation for more solubility in organic
solvents.
19
20
21
22
Recent, malononitrile, being more inexpensive, readily
industry available, less toxic, stable and easy-to-handle, had
23
been used as an alternative organic cyano-group source.
a
Key Laboratory of Functional Small Organic Molecule, Ministry of Education, Jiangxi
Province's Key Laboratory of Green Chemistry, Jiangxi Normal University, Nanchang,
Jiangxi, 330022, China. E-mail: yypeng@jxnu.edu.cn
b
Department of Chemistry, Nanchang Normal University, Nanchang 330032, China
†
Electronic supplementary information (ESI) available: Experimental procedure,
1
13
characterization data, H and C NMR spectra of compounds 3 and 4. See DOI:
1
0.1039/c9ra02979f
Scheme 1 Some previous works and this work.
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33
a
cyano-group source in one-pot C–H bond activation/ previous work, the standard iodination protocol was carried
cyanation.
out by using 1a (1.0 eq.), NIS (N-iodosuccinimide, 1.5 eq.),
ꢀ
On the other hand, quinazoline core structure exhibits [RhCp*Cl ] (1.0 mol%) and AgSbF (8.0 mol%) in DCE at 85 C
a wide range of important potential biological activities.
2
2
6
24,25
For for 30 min. When the iodination reaction was nished, the DCE
example, Erlotinib and Getinib are well-known lung cancer solvent was removed under reduced pressure, and the mixture
26
27
drugs. Prazosin is used for curing high blood pressure and of malononitrile (2.0 eq.), catalyst-system Cu
2
O (10 mol%)–L
Trimetrexate has been used in the treatment of pneumocystis (20 mol%), t-BuOK (2.0 eq.) and DMF (2.0 mL) as the solvent
2
8
ꢀ
pneumonia (Fig. 1). Thus tremendous efforts have been were added and then reacted at 120 C. To our delight, the target
devoted to develop new synthetic methods for the construction product 3a was isolated in a yield of 25% (Table 1, entry 1).
of diverse quinazoline architectures and evaluate their bioac- Various of bases, such as K CO , KOH, Cs CO , and NaOH, were
2
3
2
3
29
tivities. In the past few years, our group has focused exten- screened, and t-BuOK was found to be the best one (entries 1–5).
sively on the development methods for the synthesis of Different copper salts were then examined, and Cu O was
2
quinazoline skeletons and the late-stage functionalization of proved to be the best selected, which resulted in a yield of 58%
the quinazoline core with a wish to construct a quinazoline- (entries 6–12). The results of solvents tested indicated that trace
30
based molecular library for bioactivity assay.
2
amount of product was detected in H O or acetone (not listed in
However, the construction of quinazoline core coupling-nitrile Table 1); low yield of 47% and 49% were obtained in DMAC or
moiety had been rarely reported. In 2013, we reported palladium DMSO (entries 13 and 14). Additive KF found to be benecial to
catalyzed cyanation of quinazoline-4-tosylates with CuCN for the reaction, and gave a yield up to 63% (entry 15). Among the
31
access to quinazoline-4-nitriles (Scheme 1b). In 2017, we dis- ligands used, L (Bathocuproine) was found to be more facili-
4
closed quinazoline-directed selective ortho-iodination of 2,4-di- tating to the reaction than the others (entries 16–18). Excitingly,
arylquinazolines for the synthesis of 2-(2-iodoaryl)-4-
arylquinazolines (Scheme 1c). Very recently, iodination of 2,4- Table 1 Optimization of the reaction conditions
32
a,b
diarylquinazoline with NIS catalyzed by rhodium, and then tri-
uoromethylthiolation of the corresponding iodides for the
synthesis of SCF -substituted 2,4-diarylquinazolines was reported
3
33
in our group (Scheme 1d). Base on these, we here reported
selective synthesis of 2-(2-cyanophenyl)-4-phenylquinazolines
and 2-(2,4-dicyanophenyl)-4-phenylquinazolines by one-pot C–H
activation iodination/cyanation using malononitrile as a cyano-
group source (Scheme 1e).
Results and discussion
c
Entry
[Cu]
L
Base
Solvent
Yield
Our interest in this particular on the regioselective C–H
activation/cyanation of 2,4-diarylquinazolines originated from
1
2
3
4
5
6
7
8
9
Cu(OAc)
Cu(OAc)
Cu(OAc)
Cu(OAc)
Cu(OAc)
CuCl
2
2
2
2
2
L
L
L
L
L
L
L
L
L
L
L
L
L
L
L
L
L
L
L
L
L
L
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
2
3
4
4
4
4
4
t-BuOK
NaOH
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMAC
DMSO
DMF
DMF
DMF
DMF
25
16
21
15
18
32
24
26
48
45
58
44
47
49
63
33
57
69
84
71
75
2 2 6
our recent studies that [RhCp*Cl ] /AgSbF catalyzed iodination
33
K
2
CO
KOH
Cs CO
3
of 2,4-arylquinazoline. Here, we rst optimize the reaction
conditions of one-pot C–H iodination/cyanation of 2,4-phenyl-
quinazoline. To avoid produce mixture of mono- and bis-
functionalization products, 2-(o-methyl)phenyl-4-(p-methyl)
phenyl quinazoline 1a, which one of ortho position was blocked
by a methyl, was chosen as the model substrate for the opti-
mization of the one-pot cyanation conditions. According to our
2
3
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
CuCO
3
Cu(TFA)
CuBr
2
10
11
12
13
14
15
16
17
18
19
20
21
22
CuSO
4
Cu
CuI
2
O
Cu
2
Cu
2
Cu
2
Cu
2
Cu
2
Cu
2
Cu
2
Cu
2
Cu
2
Cu
2
O
O
O
O
O
O
O
O
O
O
t-BuOK
t-BuOK–KF
t-BuOK–KF
t-BuOK–KF
t-BuOK–KF
t-BuOK–KF
t-BuOK–KF
t-BuOK–KF
t-BuOK–KF
DMF : H
DMF : H
DMF : H
DMF : H
2
2
2
2
O ¼ 2 : 1
O ¼ 2 : 0.8
O ¼ 2 : 0.6
O ¼ 2 : 0.6
d
Trace
a
b
Optimized conditions are denoted in bold. Reaction conditions: 1a
2 2 6
(0.1 mmol), NIS (1.5 eq.). [RhCp*Cl ] (1.0 mol%)–AgSbF (8 mol%),
malononitrile (2.0 eq.) [Cu] (10 mol%)–ligand (20 mol%), base (2.0
ꢀ
c
d
eq.), in solvent (2.0 mL) at 120 C. Isolated yield. NIS was replaced
by NBS.
Fig. 1 The quinazoline core structure of drugs.
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adding 50 v% of water in DMF can improve the yield to 84% group substituent fascinated the reactions, and gave higher yields
2
(
entries 19–21) and short the reaction time from 18 h to 3 h. than that of electron-withdrawing ones. For examples, when R is
1
Finally, when NBS (N-bromosuccinimide) was used as the a methyl, and R is p-methyl or p-methoxyl, the corresponding
reactant instead of NIS under the standard reaction conditions, products 3a and 3b were obtained in excellent of yields of 84% and
only trace amount of the desired product was detected.
85%. The reaction of electron-withdrawing uorinated substrate
We then started to investigate the scope and the generality of 1d gave good yield of 59%. The substituent group at the meta or
this reaction under optimized conditions [NIS (1.5 eq.), ortho position of 4-phenyl, due to the steric hindrance, nished the
[
RhCp*Cl
2 2 6
] (1.0%), AgSbF (8.0 mol%), malononitrile (2.0 eq.), corresponding products 3e, 3f and 3g in a yield of 63%, 48% and
2
Cu
(
2
O (10 mol%), Bathocuproine (20 mol%), t-BuOK (2.0 eq.), KF 67%, respectively. When R is chloro, the reactions gave the cor-
ꢀ
2.0 eq.) in the solvent of DMF : H O ¼ 2 : 1, at 120 C for 3.5 responding products 3h–3j in good yields 79–49%.
2
hours]. The results are listed in Table 2.
Subsequently, the effects of substituent on the phenyl moiety
As shown in Table 2, a variety of 2-(o-canyophenyl)-4- of quinazoline mother ring were then examined. Pleasingly,
arylquinazolines were generated under the standard experi- methoxy and chloro functionalities were all tolerated, providing
1
2
3
mental conditions. In general, the electron-donating R , R , R
the desired products 3k–3q in good to excellent yields. 3r was
obtained in a low yield due to double electron-withdrawing
substituent effect.
a,b
2
Table 2 Substrate scope exploration
As we seen, when R is H, the reaction may produce mono-
cyanation and bis-cyanation selectivity. In our previous work,
exclusively generate mono-iodination on the 2-aryl group was
obtained catalyzed by PbCl –PPh , and then cyanation of the
2
3
corresponding 2-(2-iodoaryl)quinazolines using conventional
1e
procedure
could
selective
giving
2-(2-mono-nitrile)
quinazolines. Thus, here we focus our attention on selective
to produce bis-cyanation quinazolines in one-pot reaction. The
results are listed in Table 3.
a,b
Table 3 Substrate scope exploration
a
a
Reaction conditions: 1a (0.2 mmol), NIS (1.5 eq.), [RhCp*Cl
2
]
2
Reaction conditions: (0.2 mmol), NIS (3.0 eq.). [RhCp*Cl
(16 mol%), DEC (2.0 mL); malononitrile (4.0 eq.),
O (20 mol%), Bathocuproine (40 mol%), t-BuOK (4.0 eq.), KF (4.0
2 2
]
(
1.0 mol%), AgSbF
Cu
eq.), DMF : H
6 6
(8.0 mol%), DEC 2.0 mL, malononitrile (2.0 eq.), (2.0 mol%), AgSbF
O (10 mol%), Bathocuproine (20 mol%), t-BuOK (2.0 eq.), KF (2.0 Cu
2
2
b
b
2
O ¼ 2 : 1 (3.0 mL). Isolated yield.
eq.), DMF : H
2
O ¼ 2 : 1 (3.0 mL). Isolated yield.
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When 2,4-di-(p-methyl)phenylquinazoline 1aa was selected transmetalation to generate the active species LCu CN. The
I
as the model substrate, and the corresponding regents were LCu CN subjected to oxidative adduction with 2 to form ve-
adding double of the standard protocol above, the corre- membered cyclic Cu(III) G, and followed reductive eliminated
I
sponding bis-cyanation product 4a was obtained in a yield of to give product 3, and release the LCu X catalyst and nish the
1
2
3
6
5% (Table 3). The electron-donating R , R , R group substit- catalytic cycle.
uent also fascinating the reactions, and gave higher yields (4a, In summary, we here have developed methods for one-pot
b, 4f and 4i) than that of electron-withdrawing ones (4d, 4e, 4g process for selective the synthesis of 2-(2-cyano)aryl-4-
4
and 4h). Interestingly, dicyano-compounds were obtained in aryiquinazolines or 2-(2,6-dicyano)aryl-4-arylquinazolines. The
reasonable yields (4j and 4k) when m-substituted of 2,4-diary- one-pot reaction include two steps, the Rh-catalyzed selective
lquinazolines were used.
C–H activation iodization of 2,4-diarylquinazoline with NIS, and
In order to further explore the substrate scope, 2-phenyl- then Cu-catalyzed cyanation of the corresponding iodide
pyridine was then investigated under the standard conditions, intermediate with malononitrile to give 2-(o-cyanoaryl)-4-
however, the corresponding product 4l was obtained in 23% arylquinazolines or 2-(2,6-dicyano)aryl-4-arylquinazolines in
yield. This result again disclosed that the directing properties of good to excellent yields.
diazine in quinazoline are distinctive from that of pyridine.
To demonstrate the potential synthetic utility of this trans-
formation, a gram-scale reaction of 2-(o-methyl)phenyl-4-(p-
Experimental section
methyl)phenylquinazoline (1a) was carried out. As shown in Unless otherwise noted, commercial reagents were purchased
Scheme 2a, the cyanation product (3a) was isolated in an 71% from Aldrich, Alfa, or other commercial suppliers. All solvents
yield.
were dried and distilled according to standard procedures
To further understand the reaction mechanism, a controlled before use. Reactions were conducted in standard techniques
experiment was conducted. When 2-(2-iodo-6-methylphenyl)-4- on vacuum line. Analytical thin-layer chromatography (TLC)
(
p-methyl)phenylquinazoline (2a) was used as the reactant was performed using glass plates pre-coated with 0.25 mm 230–
under the standard reaction conditions in Scheme 2b, the 400 mesh silica gel impregnated with a uorescent indicator
cyanation product (3a) was isolated in an 92% yield.
(254 nm). Flash column chromatography was performed using
In view of the above results, a plausible mechanism was silica gel (60 A˚ pore size, 32–63 mm, standard grade). Organic
disclosed in Scheme 3. The one-pot iodination/cyanation reac- solutions were concentrated on rotary evaporators at ꢁ20 torr
ꢀ
tion include two catalytic cycles. In the rst catalytic cycle I, the (house vacuum) at 25–35 C. Nuclear magnetic resonance
reaction of [Cp*RhCl
2
]
2
and AgSbF
6
forms [Cp*Rh(SbF
6
)
2
]
2
,
(NMR) spectra are recorded in parts per million (ppm) from
which reacted with 1 through C–H activation to give ve- internal standard tetramethylsilane (TMS) on the d scale.
membered rhodacycle A, and then was oxidation adduction
with NIS to provide the Rh(IV) intermediate B, followed reduc-
tive eliminated to give iodide intermediate product 2 along with
the Rh(III) C, which was acidized to regenerate catalyst
General procedure for preparation of 2-(o-cyanoaryl)-4-
arylquinazoline 3 (3a as an example)
A mixture of 2,4-phenylquinazolines 1a (0.2 mmol), NIS
[
Cp*Rh(SbF ) ] and nish catalytic cycle I.
6 2 2
(
0.3 mmol, 1.5 eq.), [RhCp*Cl
2
]
2
(1.0 mol%), AgSbF
6
(8.0 mol%)
In the second catalytic cycle II, the ligand was incorporated
ꢀ
in DCE (2.0 mL) was stirred at 85 C, until 1a was completed
I
with Cu X to form the catalyst LCuX, and then incorporate with
malononitrile to provide the complex D, which was reacted with
t-BuOK to give intermediate E, and then undergoes
consumed (detected by TLC). The solvent was removed under
reduced pressure. A mixture of malononitrile (2.0 eq.), Cu
2
O
(10 mol%), Bathocuproin (20 mol%), t-BuOK (2.0 eq.), KF (2.0
eq.) and DMF and water (3.0 mL 2 : 1) was added and stirred at
ꢀ
1
20 C for 3 h. Aer completion of the reaction as indicated by
TLC, the mixture was cooled to room temperature. The solvent
was evaporated, residue was diluted with EtOAc (10 mL),
washed with H O (10 mL), dried by anhydrous Na SO . Evapo-
2 2 4
ration of the solvent followed purication by column chro-
matograph over silica gel provided the corresponding product
3a.
General procedure for preparation of 2-(o-dicyanoaryl)-4-
arylquinazoline 4 (4a as an example)
A mixture of 2,4-phenylquinazolines 1aa (0.2 mmol), NIS
(
0.6 mmol. 3.0 eq.), [RhCp*Cl ] (2.0 mol%), AgSbF (16 mol%)
2 2 6
ꢀ
and in DCE (2.0 mL) was stirred at 85 C for 0.5 h, until 1a was
completed consumed. The solvent was removed under reduced
pressure. A mixture of malononitrile (4.0 eq.), Cu O (20 mol%),
2
Scheme 2 A gram-scale reaction and controlled experiment.
Bathocuproin (40 mol%), t-BuOK (4.0 eq.), KF (4.0 eq.) in DMF
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Scheme 3 A plausible reaction mechanism.
ꢀ
+
and water (3.0 mL 2 : 1) was stirred at 120 C. Aer completion HRMS (ESI): m/z [M + H] calcd. for C22H16N : 322.1339;
3
of the reaction as indicated by TLC, the mixture was cooled to found: 322.1342.
room temperature. The solvent was evaporated, residue was
diluted with EtOAc (10 mL), washed with H O (10 mL), dried by Compound was obtained as a white solid: yield 59%; mp 122–
anhydrous Na SO . Evaporation of the solvent followed puri- 124 C; H NMR (400 MHz, CDCl
cation by column chromatograph over silica gel provided the 7.93 (m, 3H), 7.73–7.68 (m, 2H), 7.57 (d, J ¼ 8.0 Hz, 1H), 7.45 (t, J ¼
2-(2-Cyano-6-methylphenyl)-4-(4-uorophenyl)quinazoline (3d).
2
ꢀ
1
2
4
3
) d 8.20 (d, J ¼ 8.8 Hz, 2H), 8.01–
1
3
corresponding product 4a.
8.0 Hz, 1H), 7.32–7.27 (m, 2H), 2.49 (s, 3H). C NMR (100 MHz,
1
2
-(2-Cyano-6-methylphenyl)-4-(p-tolyl)quinazoline (3a). CDCl
3
) d 167.6, 164.1 (d, J ¼ 249.0 Hz), 160.1, 151.5, 142.2, 138.3,
4
3
Compound was obtained as a white solid: yield 84%; mp 135.2, 134.3, 133.1 (d, J ¼ 3.0 Hz), 132.4 (d, J ¼ 9.0 Hz), 131.2,
ꢀ
2
1
09–112 C; H NMR (400 MHz, CDCl ) d 8.26 (d, J ¼ 8.4 Hz, 129.3, 129.0, 128.5, 126.9, 121.5, 118.6, 115.9 (d, J ¼ 22.0 Hz),
3
+
1
H), 8.18 (d, J ¼ 8.4 Hz, 1H), 7.97 (t, J ¼ 7.6 Hz, 1H), 7.82 (d, J 113.2, 20.3. HRMS (ESI): m/z [M + H] calcd for C H FN :
22
15
3
¼
8.0 Hz, 2H), 7.73–7.63 (m, 2H), 7.56 (d, J ¼ 8.0 Hz, 1H), 340.1245, found: 340.1250.
7
.44 (t, J ¼ 7.6 Hz, 1H), 7.40 (d, J ¼ 8.0 Hz, 2H), 2.48 (s, 6H).
2-(2-Cyano-6-methylphenyl)-4-(3-methylphenyl)-quinazoline
) d 168.9, 160.2, 151.4, 142.5, (3e). Compound was obtained as a yellow oil: yield 63%; H
1
3
1
C NMR (100 MHz, CDCl
3
1
1
40.5, 138.3, 135.1, 134.1, 131.2, 130.3, 129.5, 129.1, 128.9, NMR (400 MHz, CDCl
3
) d 8.23 (d, J ¼ 8.4 Hz, 1H), 8.19 (d, J ¼
28.3, 127.4, 121.6, 118.6, 113.1, 21.5, 20.4. HRMS (ESI): m/z 8.4 Hz, 1H), 7.97 (t, J ¼ 7.6 Hz, 1H), 7.73 (s, 1H), 7.70–7.66 (m,
+
[
M + H] calcd for C23H18N : 336.1495; found: 336.1501.
3H), 7.55 (d, J ¼ 7.6 Hz, 1H), 7.49–7.37 (m, 3H), 2.48 (s, 3H), 2.47
3
13
2
-(2-Cyano-6-methylphenyl)-4-(4-methoxyphenyl)quinazoline
(s, 3H); C NMR (100 MHz, CDCl ) d 169.1, 160.2, 151.4, 142.5,
3
(
3b). Compound was obtained as a white solid: yield 85%; mp 138.6, 138.3, 136.9, 135.1, 134.2, 131.1, 131.0, 130.7, 129.1,
ꢀ
1
1
8
2
1
46–148 C; H NMR (400 MHz, CDCl
3
) d 8.20 (d, J ¼ 8.8 Hz, 1H), 128.9, 128.5, 128.3, 127.4, 121.7, 118.6, 113.1, 21.6, 20.4. HRMS
+
.09 (d, J ¼ 8.4 Hz, 1H), 7.89 (d, J ¼ 7.2 Hz, 1H), 7.83 (d, J ¼ 8.8 Hz, (ESI): m/z [M + H] calcd for C23
18 3
H N : 336.1495, found:
H), 7.63–7.57 (m, 2H), 7.47 (d, J ¼ 7.6 Hz, 1H), 7.35 (t, J ¼ 7.6 Hz, 336.1501.
1
3
H), 7.03 (d, J ¼ 8.8 Hz, 2H), 3.83 (s, 3H), 2.40 (s, 3H). C NMR
2-(2-Cyano-6-methylphenyl)-4-(2-methylphenyl)quinazoline
1
3
(100 MHz, CDCl ) d 168.3, 161.4, 160.1, 151.4, 142.5, 138.3, 135.1, (3f). Compound was obtained as a yellow oil: yield 48%; H
1
1
34.1, 132.0, 131.2, 129.5, 129.1, 128.9, 128.2, 127.3, 121.6, 118.7, NMR (400 MHz, CDCl ) d 8.20 (d, J ¼ 8.4 Hz, 1H), 7.98 (ddd, J ¼
3
+
14.2, 113.1, 55.5, 20.4. HRMS (ESI): m/z [M + H] calcd for 8.4, 6.8, 1.6 Hz, 1H), 7.76 (dd, J ¼ 8.4, 1.6 Hz, 1H), 7.67–7.61 (m,
C H N O: 352.1444; found: 352.1450.
2H), 7.54 (d, J ¼ 8.0 Hz, 1H), 7.46–7.41 (m, 3H), 7.39–7.34 (m,
2
3
18 3
13
2
-(2-Cyano-6-methyl)phenyl-4-phenylquinazoline
Compound was obtained as a colorless oil: yield 76%;
NMR (400 MHz, CDCl
3
(3c). 2H), 2.40 (s, 3H), 2.21 (s, 3H). C NMR (100 MHz, CDCl )
1
H
d 170.6, 160.5, 150.8, 142.6, 138.0, 136.3, 136.2, 134.9, 134.5,
3
) d 8.24 (dd, J ¼ 8.4, 1.6 Hz, 1H), 8.20 130.8, 130.6, 129.5, 129.3, 129.0, 128.9, 128.4, 127.3, 125.8,
+
(
d, J ¼ 8.4 Hz, 1H), 7.98 (ddd, J ¼ 8.0, 6.8, 1.6 Hz, 1H), 7.93– 122.6, 118.2, 113.0, 20.1, 20.0. HRMS (ESI): m/z [M + H] calcd
7
8
1
1
.91 (m, 2H), 7.71–7.61 (m, 2H), 7.6–7.55 (m, 4H), 7.44 (t, J ¼ for C23
H
18
N
3
: 336.1495, found: 336.1503.
2-(2-Cyano-6-methylphenyl)-4-(naphthalen-1-yl)quinazoline
60.2, 151.4, 138.3, 137.0, 135.1, 134.2, 131.2, 130.2, 130.1, (3g). Compound was obtained as a white solid: yield 67%; mp
1
3
.0 Hz, 1H), 2.48 (s, 3H). C NMR (100 MHz, CDCl ) d 168.8,
3
ꢀ
1
29.2, 128.9, 128.7, 128.4, 127.3, 121.6, 118.6, 113.2, 20.4. 148–150 C; H NMR (400 MHz, CDCl ) d 8.25 (d, J ¼ 8.4 Hz, 1H),
3
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8
7
3
1
1
1
.05 (d, J ¼ 8.0 Hz, 1H), 8.01–7.96 (m, 2H), 7.7–7.69 (m, 2H),
2-(2-Cyano-6-methylphenyl)-4-(p-tolyl)-6-chloro-quinazoline
.67–7.63 (m, 3H), 7.58–7.51 (m, 3H), 7.45–7.40 (m, 2H), 2.45 (s, (3m). Compound was obtained as a yellow solid: yield 55%; mp
1
3
ꢀ
1
H). C NMR (100 MHz, CDCl ) d 169.8, 160.6, 151.0, 142.5, 106–108 C; H NMR (400 MHz, CDCl ) d 8.22 (d, J ¼ 2.0 Hz, 1H),
3
3
38.1, 135.0, 134.7, 134.2, 133.7, 131.5, 130.9, 130.1, 129.1, 8.13 (d, J ¼ 8.8 Hz, 1H), 7.90 (dd, J ¼ 8.8, 2.4 Hz, 1H), 7.80 (d, J ¼
29.0, 128.5, 128.4, 128.1, 127.6, 127.0, 126.4, 125.8, 125.1, 8.0 Hz, 2H), 7.68 (d, J ¼ 7.6 Hz, 1H), 7.56 (d, J ¼ 8.0 Hz, 1H),
+
13
23.3, 118.4, 113.0, 20.3. HRMS (ESI): m/z [M + H] calcd for 7.46–7.41 (m, 3H), 2.48 (s, 3H), 2.47 (s, 3H). C NMR (100 MHz,
C
26
H
18
N
3
: 372.1495, found: 372.1501.
CDCl ) d 168.0, 160.4, 149.9, 142.0, 140.9, 138.3, 135.1, 135.1,
3
2
-(2-Cyano-6-chlorophenyl)-4-(p-tolyl)quinazoline (3h). 134.1, 133.6, 131.2, 130.8, 130.2, 129.7, 129.0, 126.1, 122.2,
+
Compound was obtained as a white solid: yield 79%; mp 118.5, 113.2, 21.5, 20.4. HRMS (ESI): m/z [M + H] calcd for
ꢀ
1
1
1
7
7
7
21–124 C; H NMR (400 MHz, CDCl ) d 8.26 (d, J ¼ 8.4 Hz, C H ClN : 370.1106, found: 370.1111.
3
23 17
3
H), 8.20 (d, J ¼ 8.4 Hz, 1H), 7.98 (td, J ¼ 8.46.8, 1.2 Hz, 1H),
2-(2-Cyano-6-methylphenyl)-4-(3-methylphenyl)-6-chloro-
.81 (d, J ¼ 8.0 Hz, 2H), 7.75 (ddd, J ¼ 8.0, 7.2, 0.8 Hz 2H), quinazoline (3n). Compound was obtained as a yellow oil:
1
.69 (ddd, J ¼ 8.4, 7.2, 0.8 Hz, 1H), 7.48 (t, J ¼ 8.0 Hz, 1H), yield 54%; H NMR (400 MHz, CDCl ) d 8.20 (d, J ¼ 2.0 Hz,
3
1
3
.40 (d, J ¼ 8.0 Hz, 2H), 2.47 (s, 3H). C NMR (100 MHz, 1H), 8.13 (d, J ¼ 9.2 Hz, 1H), 7.90 (dd, J ¼ 9.6, 2.0 Hz, 1H),
CDCl
3
) d 169.1, 158.3, 151.4, 141.9, 140.6, 134.6, 134.5, 7.70–7.64 (m, 3H), 7.55 (d, J ¼ 7.6 Hz, 1H), 7.51–7.40 (m, 3H),
13
1
1
34.2, 134.0, 131.7, 130.3, 129.9, 129.5, 129.2, 128.6, 127.4, 2.49 (s, 3H), 2.46 (s, 3H). C NMR (100 MHz, CDCl ) d 168.3,
3
+
22.0, 117.0, 114.9, 21.5. HRMS (ESI): m/z [M + H] calcd for 160.4, 149.9, 142.1, 138.9, 138.3, 136.4, 135.2, 135.1, 134.1,
131.3, 131.2, 130.8, 130.6, 129.1, 128.7, 127.3, 126.1, 122.2,
C23H21N O: 406.1106, found: 406.1102.
2
+
2-(2-Cyano-6-chlorophenyl)-4-(3-methylphenyl)quinazoline (3i). 118.5, 113.2, 21.6, 20.4. HRMS (ESI): m/z [M + H] calcd for
1
Compound was obtained as a yellow oil: yield 59%; H NMR (400 C23H17ClN : 370.1106, found: 370.1111.
3
MHz, CDCl
3
) d 8.25 (dd, J ¼ 8.4, 0.4 Hz, 1H), 8.21 (d, J ¼ 8.4 Hz,
2-(2-Cyano-6-methylphenyl)-4-(2-methylphenyl)-6-chloro-
1
H), 7.99 (ddd, J ¼ 8.4, 7.6, 1.6 Hz, 1H), 7.78–7.66 (m, 5H), 7.50 (d, J quinazoline (3o). Compound was obtained as a yellow oil:
1
¼
7.6 Hz, 1H), 7.47 (d, J ¼ 7.2 Hz, 1H), 7.39 (d, J ¼ 7.6 Hz, 1H), 2.48 yield 63%; H NMR (400 MHz, CDCl ) d 8.15 (d, J ¼ 9.2 Hz,
3
13
(
s, 3H). C NMR (100 MHz, CDCl
3
) d 169.3, 158.3, 151.3, 141.9, 1H), 7.90 (dd, J ¼ 9.2, 2.4 Hz, 1H), 7.72 (d, J ¼ 2.0 Hz, 1H), 7.65
1
38.7, 136.7, 134.6, 134.5, 134.3, 131.7, 131.1, 130.7, 130.0, 129.2, (d, J ¼ 7.6 Hz, 1H), 7.54 (d, J ¼ 7.6 Hz, 1H), 7.48–7.38 (m, 5H),
1
3
128.7, 128.6, 127.5, 127.4, 122.0, 117.0, 114.9, 21.5. HRMS (ESI): m/ 2.39 (s, 3H), 2.22 (s, 3H). C NMR (100 MHz, CDCl ) d 169.9,
3
+
z [M + H] calcd for C H ClN : 356.0949, found: 356.0955.
160.7, 149.4, 142.2, 138.0, 136.2, 135.6, 135.5, 135.0, 134.3,
22
15
3
2
-(2-Cyano-6-chlorophenyl)-4-(2-methylphenyl)quinazoline (3j). 130.9, 130.9, 130.8, 129.8, 129.3, 129.1, 126.0, 125.9, 123.2,
+
Compound was obtained as a yellow solid: yield 49%; mp 101– 118.2, 113.0, 20.2, 20.1. HRMS (ESI): m/z [M + H] calcd for
ꢀ
1
1
(
8
8
03 C; H NMR (400 MHz, CDCl
3
) d 8.23 (d, J ¼ 8.4 Hz, 1H), 8.00 C23H17ClN : 370.1106, found: 370.1113.
3
ddd, J ¼ 8.4, 6.8, 1.6 Hz, 1H), 7.78 (d, J ¼ 8.4 Hz, 1H), 7.74 (dt, J ¼
2-(2-Cyano-6-methylphenyl)-4-(naphthalen-1-yl)-6-chloro-
.0, 1.6 Hz, 2H), 7.66 (ddd, J ¼ 8.4, 6.8, 1.2 Hz, 1H), 7.49 (t, J ¼ quinazoline (3p). Compound was obtained as a yellow oil:
13
1
.0 Hz, 1H), 7.46–7.34 (m, 4H), 2.23 (s, 3H). C NMR (100 MHz, yield 89%; H NMR (400 MHz, CDCl ) d 8.20 (d, J ¼ 8.8 Hz,
3
CDCl ) d 170.9, 158.5, 150.9, 142.0, 136.4, 136.0, 134.7, 134.5, 134.3, 1H), 8.07 (dd, J ¼ 7.2, 1.6 Hz, 1H), 7.98 (d, J ¼ 8.0 Hz, 1H), 7.92
3
1
1
3
31.5, 130.7, 130.1, 129.6, 129.4, 129.1, 128.8, 127.3, 125.8, 123.0, (dd, J ¼ 8.8, 2.0 Hz, 1H), 7.72 (d, J ¼ 2.4 Hz, 1H), 7.72–7.63 (m,
+
16.8, 114.7, 20.0. HRMS (ESI): m/z [M + H] calcd for C H ClN : 3H), 7.62 (s, 1H), 7.57–7.53 (m, 2H), 7.48–7.41 (m,, 2H), 2.44
22
15
3
1
3
56.0949, found: 356.0951.
-(2-Cyano-6-methylphenyl)-4-(p-tolyl)-6-methoxyl quinazo- 142.1, 138.1, 135.7, 135.0, 134.30, 133.8, 133.5, 131.4, 131.0,
line (3k). Compound was obtained as a colorless oil: yield 88%; 130.80, 130.4, 129.1, 128.5, 128.1, 127.2, 126.6, 126.2, 125.5,
3
(s, 3H). C NMR (100 MHz, CDCl ) d 169.04, 160.8, 149.6,
2
1
+
H NMR (400 MHz, CDCl
3
) d 8.08 (d, J ¼ 8.8 Hz, 1H), 7.82 (d, J ¼ 125.1, 123.9, 118.3, 113.0, 20.3. HRMS (ESI): m/z [M + H]
8
1
(
.0 Hz, 2H), 7.66 (d, J ¼ 7.2 Hz, 1H), 7.61 (dd, J ¼ 9.2, 2.8 Hz, calcd for C26H17ClN : 406.1106, found: 406.1102.
3
H), 7.54 (d, J ¼ 7.6 Hz, 1H), 7.50 (d, J ¼ 2.8 Hz, 1H), 7.43–7.38
2-(2-Cyano-6-chlorophenyl)-4-(2-methylphenyl)-6-methoxyl
1
3
m, 3H), 3.89 (s, 3H), 2.48 (s, 3H), 2.46 (s, 3H). C NMR (100 quinazoline (3q). Compound was obtained as a yellow oil: yield
1
MHz, CDCl ) d 167.0, 159.0, 158.3, 147.6, 142.6, 140.2, 138.3, 72%; H NMR (400 MHz, CDCl ) d 8.12 (d, J ¼ 9.2 Hz, 1H), 7.72
3
3
1
1
C
35.0, 134.5, 131.1, 130.6, 129.9, 129.5, 128.7, 126.8, 122.6, (ddd, J ¼ 9.2, 8.0, 1.2 Hz, 2H), 7.63 (dd, J ¼ 9.6, 2.8 Hz, 1H), 7.49–
+
13.2, 104.5, 55.8, 21.5, 20.4. HRMS (ESI): m/z [M + H] calcd for 7.34 (m, 5H), 6.96 (d, J ¼ 2.8 Hz, 1H), 3.80 (s, 3H), 2.24 (s, 3H).
1
3
24
H
20
N
3
O: 366.1601, found: 366.1606.
C NMR (100 MHz, CDCl ) d 168.8, 159.3, 156.4, 147.1, 142.1,
3
2-(2-Cyano-6-methylphenyl)-4-(3-methylphenyl)-6-methoxylquin- 136.3, 136.3, 134.6, 134.3, 131.4, 130.8, 130.6, 129.9, 129.5,
azoline (3l). Compound was obtained as a colorless oil: yield 75%; 129.2, 127.5, 125.9, 124.0, 116.9, 114.8, 104.2, 55.8, 20.0. HRMS
1
+
H NMR (400 MHz, CDCl ) d 8.09 (d, J ¼ 9.2 Hz, 1H), 7.74 (s, 1H), (ESI): m/z [M + H] calcd for C H ClN O: 386.1055, found:
3
23 17
3
7
2
2
1
.6.9 (d, J ¼ 8.0 Hz, 1H), 7.66 (d, J ¼ 8.4 Hz, 1H), 7.62 (dd, J ¼ 9.2, 386.1057.
.8 Hz, 1H), 7.54 (d, J ¼ 7.6 Hz, 1H), 7.49–7.37 (m, 4H), 3.88 (s, 3H),
(2-Cyano-6-methylphenyl)-4-(4-uorophenyl)-6-chloro-2-
) d 167.2, 159.0, quinazoline (3r). Compound was obtained as a yellow solid:
13
.48 (s, 3H), 2.45 (s, 3H). C NMR (100 MHz, CDCl
3
ꢀ
1
58.3, 147.6, 142.6, 138.7, 138.3, 137.3, 135.0, 131.1, 130.8, 130.6, yield 29%; mp: 126–128 C; H NMR (400 MHz, CDCl ) d 8.17 (d,
3
1
30.5, 128.7, 128.5, 126.93, 126.9, 122.6, 118.6, 113.2, 104.5, 55.8, J ¼ 2.0 Hz, 1H), 8.15 (d, J ¼ 8.8 Hz, 1H), 7.95–7.91 (m, 3H), 7.69
+
21.6, 20.3. HRMS (ESI): m/z [M + H] calcd for C24
H
20
N
3
O: 366.1601, (d, J ¼ 7.2 Hz, 1H), 7.57 (d, J ¼ 8.0 Hz, 1H), 7.46 (t, J ¼ 8.0 Hz,
found: 366.1606.
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1
3
ꢀ
1
1
H), 7.34–7.29 (m, 2H), 2.48 (s, 3H). C NMR (100 MHz, CDCl
3
)
153 C; H NMR (400 MHz, CDCl
3
) d 8.31 (d, J ¼ 8.4 Hz, 1H), 8.25 (d,
1
d 166.8, 164.4 (d, J ¼ 238.0 Hz), 163.0, 150.0, 141.8, 138.3, J ¼ 8.4 Hz, 1H), 8.03 (d, J ¼ 8.8 Hz, 2H), 7.98 (ddd, J ¼ 8.4, 6.8,
3
4
1
1
1
3
35.3(d, J ¼ 11.0 Hz) 134.4, 132.5( J ¼ 3.0 Hz), 123.4, 132.3, 1.2 Hz, 1H), 7.86 (s, 2H), 7.71 (ddd, J ¼ 8.4, 6.8, 1.2 Hz, 1H), 7.14 (d, J
2
13
31.3, 131.0, 129.2, 125.7, 122.0, 118.6, 116.2 (d, J ¼ 21.0 Hz), ¼ 8.8 Hz, 2H), 3.92 (s, 3H), 2.53 (s, 3H). C NMR (100 MHz, CDCl )
3
+
13.2, 20.4. HRMS (ESI): m/z [M + H] calcd for C22
H
14ClFN
3
:
d 168.6, 161.7, 156.2, 151.5, 142.5, 140.6, 138.3, 134.3, 132.3, 129.4,
129.3, 128.8, 127.4, 122.0, 117.3, 114.5, 114.3, 55.5, 20.8; HRMS
74.0855, found: 374.0860.
+
2
-(2,6-Dicyano-4-methylphenyl)-4-(p-tolyl)quinazoline (4a). (ESI): m/z [M + H] calcd for C24
H
17 4
N O: 377.1397, found: 377.1404.
Compound was obtained as a white solid: yield 65%; mp 158–
2-(2,6-Dicyano-4-methylphenyl)-4-(4-chlorophenyl)quinazoline
ꢀ
1
1
1
1
1
60 C; H NMR (400 MHz, CDCl
3
) d 8.30 (dd, J ¼ 8.4, 1.2 Hz, (4g). Compound was obtained as a yellow solid: yield 65%; mp:
ꢀ
1
H), 8.26 (dd, J ¼ 8.4, 1.2 Hz, 1H), 8.00 (ddd, J ¼ 8.4, 6.8, 1.2 Hz, 187–190 C; H NMR (400 MHz, CDCl ) d 8.28 (d, J ¼ 8.4 Hz, 1H),
3
H), 7.93 (d, J ¼ 8.0 Hz, 2H), 7.70 (s, 2H), 7.71 (ddd, J ¼ 8.4, 6.8, 8.22 (d, J ¼ 8.0 Hz, 1H), 8.01(ddd, J ¼ 8.0, 6.8, 1.2 Hz, 1H), 7.97 (d, J
1
3
.2 Hz, 1H), 7.42 (d, J ¼ 8.0 Hz, 2H), 2.53 (s, 3H), 2.49 (s, 3H).
C
¼ 8.4 Hz, 2H), 7.87 (s, 2H), 7.73 (ddd, J ¼ 8.0, 6.8, 1.2 Hz, 1H), 7.60
13
NMR (100 MHz, CDCl
1
1
3
) d 169.2, 156.3, 151.4, 142.4, 140.8, 140.6, (d, J ¼ 8.4 Hz, 2H), 2.53 (s, 3H). C NMR (100 MHz, CDCl
38.3, 134.4, 133.9, 130.5, 129.5, 129.3, 128.9, 127.4, 122.0, 156.2, 151.5, 142.1, 140.8, 138.3, 136.9, 135.1, 134.6, 131.9, 129.6,
17.3, 114.5, 21.5, 20.8. HRMS calcd. For C24 : 361.1448, 129.2, 129.1, 126.8, 121.8, 117.2, 114.5, 20.8. HRMS (ESI): m/z [M +
3
) d 167.8,
17 4
H N
+
found: 361.1452.
-(2,6-Dicyano-4-methoxyphenyl)-4-(p-tolyl)quinazoline (4b).
Compound was obtained as a white solid: yield 72%; mp 194– (4h). Compound was obtained as a yellow solid: yield 54%; mp
H] calcd for C23
4
H14ClN : 381.0902, found: 381.0907.
2
2-(2,6-Dicyano-4-methylphenyl)-4-(4-uorophenyl)quinazoline
ꢀ
1
ꢀ
1
1
1
1
7
96 C; H NMR (400 MHz, CDCl ) d 8.29 (dd, J ¼ 8.8, 1.2 Hz, 209–212 C; H NMR (400 MHz, CDCl ) d 8.28 (d, J ¼ 8.4 Hz, 1H),
3
3
H), 8.25 (d, J ¼ 9.2, 1.2 Hz, 1H), 7.98 (ddd, J ¼ 8.4, 6.8, 1.2 Hz 8.24 (d, J ¼ 8.4 Hz, 1H), 8.06–8.0 (m, 3H), 7.87 (s, 2H), 7.74 (ddd, J
1
3
H), 7.92 (d, J ¼ 8.0 Hz, 2H), 7.70 (ddd, J ¼ 8.4, 7.6, 1.2 Hz 1H), ¼ 8.0, 7.6, 1.2 Hz, 1H), 7.31 (t, J ¼ 8.4 Hz, 2H), 2.53 (s, 3H).
C
1
3
1
.55 (s, 2H), 7.42 (d, J ¼ 8.0 Hz, 2H), 3.96 (s, 3H), 2.49 (s, 3H).
C
NMR (100 MHz, CDCl
3
) d 166.7(d, J ¼ 243.0 Hz), 156.2, 151.5,
4 3
NMR (100 MHz, CDCl
3
) d 169.1, 159.7, 156.1, 151.5, 140.8, 137.3, 142.2, 140.8, 138.3, 134.6, 132.8 (d, J ¼ 3.0 Hz), 132.7 (d, J ¼ 9.0
2
1
1
34.3, 134.0, 130.5, 129.5, 129.3, 128.7, 127.4, 123.4, 122.0, Hz), 129.5, 129.1, 127.0, 121.9, 117.2, 116.1, 116.0 (d, J ¼ 22.0
+
+
17.1, 115.7, 56.4, 21.5. HRMS (ESI): m/z [M + H] calcd for Hz), 114.5, 20.8; HRMS (ESI): m/z [M + H] calcd for C23
365.1197, found: 365.1121.
2-(2,6-Dicyano-4-methylphenyl)-4-(p-tolyl)-6-methoxylquinazoline
was obtained as a colorless oil: yield 53%; H NMR (400 MHz, (4i). Compound was obtained as a white solid: yield 68%; mp 156–
4
H14FN :
C H N O: 377.1397, found: 377.1402.
2
4
17 4
2
-(2,6-Dicyanophenyl)-4-(p-tolyl)quinazoline (4c). Compound
1
ꢀ
1
CDCl
3
) d 8.31 (d, J ¼ 8.4 Hz, 1H), 8.27 (d, J ¼ 8.4 Hz, 1H), 8.07 (d, J 159 C; H NMR (400 MHz, CDCl
3
) d 8.16 (d, J ¼ 9.2 Hz, 1H), 7.93 (d,
¼
7.6 Hz, 2H), 8.01 (t, J ¼ 8.0 Hz, 1H), 7.93 (d, J ¼ 8.0 Hz, 2H), J ¼ 8.0 Hz, 2H), 7.84 (s, 2H), 7.63 (dd, J ¼ 9.2, 2.8 Hz, 1H), 7.54 (d, J ¼
1
3
7
.76–7.67 (m, 2H), 7.43 (d, J ¼ 8.0 Hz, 2H), 2.49 (s, 3H). C NMR 2.8 Hz, 1H), 7.42 (d, J ¼ 8.0 Hz, 2H), 3.90 (s, 3H), 2.51 (s, 3H), 2.48 (s,
13
(100 MHz, CDCl
3
) d 169.3, 156.2, 151.4, 145.2, 140.9, 137.7, 134.6, 3H). C NMR (100 MHz, CDCl
3
) d 167.2, 159.5, 154.4, 147.6, 142.6,
1
33.9, 130.5, 129.7, 129.6, 129.4, 129.1, 127.5, 122.1, 117.1, 114.7, 140.5, 140.2, 138.2, 134.3, 130.8, 130.1, 129.5, 127.1, 123.1, 117.3,
+
+
21.6. HRMS (ESI): m/z [M + H] calcd for C H N : 347.1291, 114.4, 104.6, 55.8, 21.5, 20.7. HRMS (ESI): m/z [M + H] calcd for
23 15 4
found: 347.1294.
C H N O: 391.1553, found: 391.1558.
25 19 4
2-(2,6-Dicyano-4-chlorophenyl)-4-(p-tolyl)quinazoline (4d).
2-(2,6-Dicyano-3-methylphenyl)-4-(p-tolyl)quinazoline (4j).
Compound was obtained as a yellow solid: yield 47%; mp: 172– Compound was obtained as a white solid: yield 68%; mp 128–
ꢀ
1
ꢀ
1
1
(
7
75 C; H NMR (400 MHz, CDCl
3
) d 8.31 (d, J ¼ 8.0 Hz, 1H), 8.26 130 C; H NMR (400 MHz, CDCl ) d 8.34 (s, 1H), 8.22 (dd, J ¼
3
d, J ¼ 8.4 Hz, 1H), 8.04–8.00 (m, 3H), 7.92 (d, J ¼ 8.4 Hz, 2H), 8.4, 3.6 Hz, 2H), 7.94–7.89 (m, 3H), 7.75 (d, J ¼ 8.0 Hz, 1H), 7.62
1
3
.74 (t, J ¼ 7.6 Hz, 1H), 7.43 (d, J ¼ 7.6 Hz, 2H), 2.49 (s, 3H).
) d 169.4, 155.4, 151.4, 143.3, 141.0, 137.5, 1H), 2.51 (s, 3H), 2.48 (s, 3H). C NMR (100 MHz, CDCl
36.0, 134.6, 133.7, 130.5, 129.6, 129.4, 129.2, 127.5, 122.1, d 168.8, 158.5, 151.7, 143.4, 141.3, 140.6, 134.9, 134.3, 134.0,
C
(t, J ¼ 8.0 Hz, 1H), 7.41 (d, J ¼ 8.0 Hz, 2H), 7.35 (d, J ¼ 7.6 Hz,
13
NMR (100 MHz, CDCl
3
3
)
1
1
+
16.1, 116.0, 21.6. HRMS (ESI): m/z [M + H] calcd for 131.3, 130.7, 130.6, 129.4, 129.2, 128.0, 127.3, 121.8, 119.7,
C H ClN : 381.0902, found: 381.0907.
+
109.4, 21.9, 21.5. HRMS (ESI): m/z [M + H] calcd for C H N :
24 17 4
2
3
14
4
2-(2,6-Dicyano-4-uorophenyl)-4-(p-tolyl)quinazoline
(4e). 361.1448, found: 361.1452.
Compound was obtained as a yellow solid: yield 62%; mp: 170–
2-(2,6-Dicyano-3-chlorophenyl)-4-(p-tolyl)quinazoline (4k).
ꢀ
1
1
1
7
8
73 C; H NMR (400 MHz, CDCl
3
) d 8.30 (dd, J ¼ 8.4, 0.4 Hz, Compound was obtained as a yellow solid: yield 37%; mp: 157–
ꢀ
1
H), 8.26 (d, J ¼ 8.4 Hz, 1H), 8.01 (ddd, J ¼ 8.4, 7.2, 1.2 Hz, 1H), 160 C; H NMR (400 MHz, CDCl ) d 8.31 (d, J ¼ 8.4 Hz, 1H), 8.26
3
.91 (d, J ¼ 8.0 Hz, 2H), 7.78 (d, J ¼ 7.6 Hz, 2H), 7.73 (ddd, J ¼ (d, J ¼ 8.4 Hz, 1H), 8.02 (ddd, J ¼ 8.4, 7.2, 1.2 Hz, 1H), 7.96 (d, J ¼
1
3
.4, 7.2, 1.2 Hz, 1H), 7.42 (d, J ¼ 8.0 Hz, 2H), 2.49 (s, 3H).
C
8.4 Hz, 1H), 7.91 (d, J ¼ 8.0 Hz, 2H), 7.77–7.73 (m, 2H), 7.43 (d, J
1
13
NMR (100 MHz, CDCl ) d 169.4, 161.4 (d, J ¼ 254.0 Hz), 155.4, ¼ 7.6 Hz, 2H), 2.49 (s, 3H). C NMR (100 MHz, CDCl ) d 169.4,
3
3
3
1
1
51.4, 141.7 (d, J ¼ 4.0 Hz), 141.0, 134.6, 133.8, 130.5, 129.5, 155.8, 151.4, 147.5, 142.9, 141.0, 137.5, 134.6, 133.7, 130.6,
2
3
29.3, 129.1, 127.5, 125.1 (d, J ¼ 24.0 Hz), 122.1, 116.5 (d, J ¼ 130.5, 129.5, 129.4, 129.3, 127.5, 122.3, 116.3, 115.6, 113.9,
4
+
+
10.0 Hz), 116.0 (d, J ¼ 2.0 Hz), 21.5. HRMS (ESI): m/z [M + H]
112.9, 21.5. HRMS (ESI): m/z [M + H] calcd for C23
H
14ClN
4
:
+
+
calcd for C23
H
14FN
4
[M + H] 365.1197, found: 365.1121.
381.0902, found: 381.0907.
2
-(2,6-Dicyano-4-methylphenyl)-4-(4-methoxyphenyl)quinazoline
2-(2,6-Dicyanophenyl)pyridine (4l). Compound was obtained
ꢀ
(
4f). Compound was obtained as a white solid: yield 72%; mp 149– as a white solid: yield 23%; mp 140–142 C; 1H NMR (400 MHz,
18262 | RSC Adv., 2019, 9, 18256–18264
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CDCl
RSC Advances
3
) d 8.78 (d, J ¼ 4.8 Hz, 1H), 7.86–7,78 (m, 3H), 7.72–7.68
and K. Ohe, Chem. Commun., 2011, 2375–2377; (c)
K. Okamoto, M. Watanabe, M. Murai, R. Hatano and
K. Ohe, Chem. Commun., 2012, 3127–3129.
8 (a) N. Chatani and T. Hanafusa, J. Org. Chem., 1986, 51, 4714–
4716; (b) M. Sundermeier, S. Mutyala, A. Zapf,
A. Spannenberg and M. Beller, J. Organomet. Chem., 2003,
(
1
1
m, 1H), 7.51 (td, J ¼ 7.6, 1.2 Hz, 1H), 7.37 (ddd, J ¼ 7.6, 4.8,
1
3
.2 Hz, 1H). C NMR (101 MHz, CDCl ) d 155.3, 150.0, 143.5,
3
34.1, 132.8, 131.0, 130.0, 128.7, 123.3, 123.2. HRMS (ESI): m/z
+
[M + H] calcd for C12
H
9
N
2
: 181.0760, found: 181.0769.
6
84, 50–55.
Conflicts of interest
9
(a) W. Zhou, L. Zhang and N. Jiao, Angew. Chem., Int. Ed.,
2009, 48, 7094–7097; (b) W. Zhou, J. Xu, L. Zhang and
N. Jiao, Org. Lett., 2010, 12, 2888–2891.
There are no conicts to declare.
1
0 (a) T. Schareina, A. Zapf and M. Beller, Chem. Commun.,
Acknowledgements
2
004, 1388–1389; (b) T. Schareina, A. Zapf, W. M ¨a gerlein,
Financial support from National Natural Science Foundation of
China (no. 21762020), Jiangxi Provincial Department of Science
and Technology (no. 20171BAB203006), and key laboratory of
Functional Small Organic Molecule, Ministry of Education,
Jiangxi Normal University (no. KLFS-KF-201702) is gratefully
acknowledged.
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