Molecular Iodine Catalysed Benzylic sp 3 C-H Bond Amination for the Synthesis of 2-Arylquinazolines from 2-Aminobenzaldehydes, 2-Aminobenzophenones and 2-Aminobenzyl Alcohols

Article abstract of DOI:10.1055/s-0037-1609200

Molecular iodine catalysed benzylic sp ³ C-H bond amination has been developed for the synthesis of quinazolines from 2-aminobenzaldehydes and 2-aminobenzophenones with benzylamines. The use of oxygen as a green oxidant combined with the transition-metal-, additive- and solvent-free conditions makes the methodology economical and greener. The lack of aqueous work up also enhances the efficiency of this protocol. A series of 2-arylquinazolines was synthesised in good to excellent yields by using the developed protocol. 2-Aminobenzyl alcohols could also be employed to prepare the corresponding quinazoline derivatives.

Full text of DOI:10.1055/s-0037-1609200

SYNLETT
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
© Georg Thieme Verlag Stuttgart · New York
2018, 29, A–G
letter
A
en
D. S. Deshmukh, B. M. Bhanage
Letter
Synlett
Molecular Iodine-Catalysed Benzylic sp3 C–H Bond Amination for
the Synthesis of 2-Arylquinazolines from 2-Aminobenzaldehydes,
2-Aminobenzophenones and 2-Aminobenzyl Alcohols
Dewal S. Deshmukh
R
Bhalchandra M. Bhanage*
0
0
0
0
0-
0
0
1
9-
5
3
8
3-
3
3
9
O
R1
R
N
Department of Chemistry, Institute of Chemi-
cal Technology, Matunga, Mumbai-400019,
India
NH2
I2, O2
N
NH2
R2
R1
+
or
bm.bhanage@ictmumbai.edu.in
OH
NH2
R1
R2
• 18 examples with 49 to 92 % yield
• R = H, Ph; R1 = H, Cl, Br; R2 = H, Me,
OMe, Cl, F, NO2, etc.
• Transition-metal free
• Additive and solvent free
• Use of O2 as a green oxidant
Received: 27.10.2017
Accepted after revision: 18.12.2017
Published online: 29.01.2017
tion, Michael additions, oxidation reactions, protection–
deprotection of functional groups, Prins related reactions
and functionalisation of alcohols.11
DOI: 10.1055/s-0037-1609200; Art ID: st-2017-d0793-l
Quinazolines and their derivatives show a wide range of
biological properties including antimicrobial, anticancer,
cytotoxic, analgesic, anti-inflammatory, antidiabetic, anti-
depressant, anti-Parkinsonian, phosphodiesterase inhibi-
tory, antitubercular, antimalarial and antihypertensive
activities.12 A number of synthetic methods have been doc-
umented for the preparation of quinazoline derivatives, in-
cluding coupling of 2-aminobenzylamines,13 2-aminobenzyl
alcohols,14 2-halobenzyl alcohols,15 2-halobenzylamine,16
2-halobenzyl tosylates,17 2-halobenzyl bromides,18 2-nitro-
benzaldehyde oxime19 and 2-nitrophenones20 with differ-
ent aryl precursors. In addition, the synthesis of 2-aryl-
quinazolines from carbonyl compounds, which generally
proceeds through condensation with arylamines followed
by cyclisation, has been well documented.21 In 2010, Wang
et al. reported the oxidative cyclisation of 2-aminobenzo-
phenones with benzylamines in the presence of molecular
iodine as catalyst and tert-butyl hydroperoxide oxidant
(Scheme 1).22 Subsequently, Han et al. reported a protocol
using 2-aminobenzaldehydes and 2-aminobenzophenones
with benzylamine in the presence of 4-hydroxy-TEMPO/O2
in o-xylene at elevated temperatures and extended reaction
periods.23 Recently, Gopalaiah and co-workers reported the
synthesis of 2-arylquinazolines by using an iron-catalysed
cascade reaction of 2-aminobenzyl alcohols with benzyl-
amines.24 Nevertheless, there continues to be the need to
develop new protocols for the synthesis of 2-arylquinazo-
lines from 2-aminobenzaldehydes and 2-aminobenzo-
phenones with benzylamines, which can overcome the lim-
itations of previous reports.
Abstract Molecular iodine catalysed benzylic sp3 C–H bond amination
has been developed for the synthesis of quinazolines from 2-amino-
benzaldehydes and 2-aminobenzophenones with benzylamines. The
use of oxygen as a green oxidant combined with the transition-metal-,
additive- and solvent-free conditions makes the methodology econom-
ical and greener. The lack of aqueous work up also enhances the effi-
ciency of this protocol. A series of 2-arylquinazolines was synthesised in
good to excellent yields by using the developed protocol. 2-Amino-
benzyl alcohols could also be employed to prepare the corresponding
quinazoline derivatives.
Key words transition-metal free, benzylic sp3 amination, 2-aryl-
quinazoline, molecular iodine, oxygen
The direct functionalisation of an sp3 C–H bond into a
C–N bond has emerged as a powerful strategy in organic
synthesis because it improves the overall efficiency of the
desired transformations. It not only avoids the additional
prefunctionalisation of starting material but also provides
greener and more economical strategies than conventional
cross-coupling reactions.1 Benzylic sp3 C–H/N–H coupling
reactions have been extensively studied in the presence of
transition metals such as cobalt,2 copper,3 iridium,4 ruthe-
nium,5 rhenium6 and palladium.7 Alternatively, transition-
metal-free protocols for the functionalisation of benzylic
sp3 C–H bonds have also been well documented in recent
years.8 Various heterocycles have been synthesised through
intra- or intermolecular pathways via functionalisation of
benzylic sp3 C–H/N–H coupling.9
Molecular iodine is an established catalyst in organic
synthesis.10 Being mildly Lewis acidic in nature, it acts as an
efficient and versatile reagent for reactions such as iodina-
In a continuation to our research in the area of green
and sustainable chemistry,25 we report herein a highly effi-
cient, green and sustainable protocol for the synthesis of
© Georg Thieme Verlag Stuttgart · New York — Synlett 2018, 29, A–G

B
D. S. Deshmukh, B. M. Bhanage
Letter
Synlett
Previous reports
R
• TBHP as a toxic oxidant
• Poor yields with aldehydes
Ref. 22
NH2
O
R2
R1
+
a.
NH2
R
O
N
NH2
NH2
• Use of TEMPO in toxic solvent
R1
R1
R2
+
+
b.
c.
Ref. 23
NH2
N
R2
• Metal catalyst in hazardous solvent
OH
R1
R2
Ref. 24
NH2
This work
R
• Metal and solvent free
O
R1
• Molecular O2 as a green oxidant
• Wide substrate scope
NH2
N
NH2
R2
R1
+
or
N
OH
NH2
R1
R2
Scheme 1 Synthesis of 2-arylquinazolines
quinazolines from 2-aminobenzaldehydes and 2-amino-
benzophenones with aryl amines in the presence of molec-
ular iodine. Notably, the reaction works very well for both
2-aminobenzaldehydes and 2-aminobenzophenones under
solvent-free conditions in short reaction times. Moreover,
2-aminobenzyl alcohols could also be converted into their
corresponding quinazolines.
(entry 6). When the reaction was attempted without sol-
vent, there was no substantive decrease in yield of 3a (entry
7). Different concentrations of molecular iodine were tested
(entries 8–10) and it was found that 10 mol% of molecular
Table 1 Optimization of Reaction Conditionsa
O
Our preliminary studies focused on the synthesis of
2-arylquinazolines from 2-aminobenzaldehydes and benzyl-
amines in the presence of molecular iodine as a catalyst in
dimethyl sulfoxide (DMSO). On reacting 2-amino-5-chloro-
benzaldehyde (1a) with benzylamine (2a) at 80 °C for 24 h
under an oxygen balloon, the desired product 6-chloro-2-
phenylquinazoline (3a) was obtained in 84% yield (Table 1,
entry 1). Next, the reaction was performed at different in-
tervals of time and it was found that the reaction time
could be reduced to 12 h from 24 h (entries 2 and 3); al-
though considerable decrease in the yield of 3a was ob-
served when the reaction was performed for less time (en-
try 3). This may be due to the fact that the reaction pro-
ceeds through initial imine formation. In the next set of
experiments, the reaction was carried out at different reac-
tion temperatures (entries 4–6). No significant increase in
the yield of the desired product 3a was noted when reac-
tion was performed at 90 °C (entry 4) and performing reac-
tion at 70 °C led to decrease in the yield of desired product
3a (entry 5). Interestingly, the desired product 3a was ob-
tained in a very good yield when the reaction was carried
out at 130 °C for just 3 h; however, a decrease in the yield
was noted when the reaction was performed at 120 °C
Cl
Cl
I2, O2,
Solvent
N
H
NH2
+
N
NH2
Temp (°C),
Time (h)
3a
1a
2a
Entry
I2 (mol%)
Solvent
Temp (°C)
Time (h)
Yield (%)b
1
2
20
20
20
20
20
20
20
15
10
5
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
–
80
80
24
12
6, 8
12
12
3
84
83
3
80
71, 74
84
4
90
5
70
76
6
130, 120
130
130
130
130
130
84, 77
82
7
3
8
–
3
82
9
–
3
82
10
11c
–
3
64
10
–
3
41
a Reaction conditions: 2-amino-5-chlorobenzaldehydes (1a, 0.5 mmol),
benzylamines (2a, 1.5 mmol).
b GC yield.
c Without oxygen.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2018, 29, A–G

C
D. S. Deshmukh, B. M. Bhanage
Letter
Synlett
iodine was necessary for this reaction (entry 9). Further de-
creasing the concentration of molecular iodine to 5 mol%
led to a decrease in yield of 3a (entry 10). We also observed
that the absence of oxygen reduced the yield of product
(entry 11). Thus, the optimised reaction conditions were
selected as 2-amino-5-chlorobenzaldehydes (1a, 0.5 mmol),
benzylamine (2a, 1.5 mmol) and I2 (10 mol%) under an O2
atmosphere at 130 °C for 3 h. With 2-aminobenzophenones,
the optimised reaction parameters found to be 2-amino-
benzophenone (1d, 0.5 mmol), benzylamine (2a, 1.5 mmol)
and I2 (10 mol%) under O2 atmosphere at 130 °C for 8 h. (see
the Supporting Information for the optimization of the ex-
perimental conditions for the reaction of 1d with 2a).
With the optimised reaction conditions in hand, a range
of 2-aminobenzaldehydes and benzylamines were investi-
gated as starting reactants for the synthesis of 2-aryl-
quinazolines; the corresponding results are shown in Table
2. The reaction of 1a with 2a provided 82% isolated yield of
the desired product 3a (entry 1) under the optimised reac-
tion conditions. The effect of electron-donating and -with-
drawing groups on benzylamine was examined and it was
observed that substituents that increase electron density
on the benzene ring of benzylamines favour the reaction,
presumably because this favours formation of the interme-
diate imine. The reaction of 1a with p-methoxybenzyl-
amine (2b) and p-fluorobenzylamine (2c) proceeded
smoothly and furnished products 3b and 3c with 88% and
79% yields, respectively (entries 2 and 3). Reaction of 2-am-
inobenzaldehyde (1b) with benzylamine (2a) was found to
give 2-phenylquinazoline 3d in 86% yield (entry 4). Study-
ing the scope of the reaction with 2-aminobenzaldehyde
(1b) and substituted benzylamines for the synthesis of 2-aryl-
quinazolines revealed that the corresponding desired prod-
ucts 3e and 3f were obtained in excellent yield with benzyl-
amines having electron-donating substituents at the para-
position (entries 5 and 6). The reaction of 1b with benzyl-
amines having electron-withdrawing groups at the para-
position produced the corresponding products 3g and 3h in
good yields (entries 7 and 8). Benzylamines with -OMe, -NO2
and -Cl substituents at the meta-position had little effect on
the product yield (entries 9–11). Heteroaromatic benzyl-
amines such as pyridin-3-ylmethanamine (2i), furan-2-yl-
methanamine (2j) and thiophen-2-ylmethanamine (2k)
were also examined and products 3l, 3m and 3n were
formed in 86%, 76% and 80% yields, respectively (entries 12–
14). Reaction of 2-amino-3,5-dibromobenzaldehyde (1c)
with 2a and 2c led to the desired arylquinazolines 3o and 3p
in 75% and 68% yields, respectively (entries 15 and 16).
Table 2 Synthesis of 2-Aryl quinazolines from 2-Aminobenzaldehydes and 2-Aminobenzophenonesa
O
I2 (10 mol%),
N
R
NH2
R1
O2
R1
R2
+
N
R2
NH2
130 °C, 3 h
2
1
3
Entry
1
1
2
Product (3)
Yield (%)b
Cl
O
N
Cl
NH2
H
N
N
82
NH2
2a
2b
1a
3a
Cl
N
NH2
2
1a
1a
88
O
O
3b
Cl
N
NH2
N
3
4
79
86
F
F
2c
3c
O
N
H
N
2a
NH2
1b
3d
© Georg Thieme Verlag Stuttgart · New York — Synlett 2018, 29, A–G

D
D. S. Deshmukh, B. M. Bhanage
Letter
Synlett
Table 2 (continued)
Entry
1
2
Product (3)
Yield (%)b
N
N
NH2
N
5
1b
1b
1b
84
2d
2b
3e
3f
N
N
N
N
6
7
92
78
O
N
N
N
NH2
Cl
Cl
2e
3g
8
9
1b
1b
1b
1b
1b
2c
73
82
69
74
86
F
3h
3i
NH2
O
O
2f
N
N
N
NH2
NO2
N
N
N
10
11
12
NO2
2g
3j
NH2
Cl
Cl
2h
2i
3k
NH2
N
N
3l
N
N
NH2
O
S
13
14
1b
1b
76
80
N
N
O
2j
3m
3n
NH2
S
2k
© Georg Thieme Verlag Stuttgart · New York — Synlett 2018, 29, A–G

E
D. S. Deshmukh, B. M. Bhanage
Letter
Synlett
Table 2 (continued)
Entry
15
1
2
Product (3)
Yield (%)b
O
H
Br
N
Br
2a
N
75
NH2
Br
Br
3o
1c
Br
N
N
16
1c
2c
68
88
Br
F
3p
NH2
O
17c
2a
N
N
1d
3q
NH2
O
Cl
18c
2a
81
N
N
Cl
1e
3r
a Reaction conditions: 1 (0.5 mmol), 2 (1.5 mmol).
b GC yield.
c Reaction performed for 8 h.
The reaction of 2-aminobenzophenone (1d) and 2-amino-
5-chlorobenzophenone (1e) with 2a led to products 3q and
3r, in 88% and 81% yields, respectively (Table 2, entries 17
and 18). After screening aromatic amines successfully,
aliphatic and unsaturated amines such as hexylamine, allyl-
amine hydrochloride and cinnamylamine were also exam-
ined under the established protocol. Unfortunately, none of
these amines could be converted into the desired products.
Having established an efficient synthesis of 2-aryl-
quinazolines from 2-aminobenzaldehydes and 2-amino-
benzophenones, the synthesis of 2-arylquinazoline from
2-aminobenzyl alcohol 4 was then attempted. Gratifyingly,
we succeed in synthesising 2-arylquinazoline directly from
2-aminobenzyl alcohol (4) and benzylamine (2a). A broad
range of readily available benzylamines were screened for
the synthesis of 2-arylquinazolines from 2-aminobenzyl
alcohol (4), as summarised in Table 3. Although good toler-
ance for benzylamines substituted with electron-donating
as well as -withdrawing groups was observed, the yields with
these substrates were moderate. The reaction of 2-amino-
benzyl alcohol with benzylamines having meta- and para-
substituents delivered the corresponding 2-arylquinazoline
products in moderate yields (entries 1–5). Furthermore,
thiophen-2-ylmethanamine (2k) also provided product 3n′
in 55% yield (entry 6).
In summary, we have reported an efficient and simple
method for the synthesis of 2-arylquinazolines from 2-amino-
benaldehydes or 2-aminobenzophenones with benzyl-
amines in very good to excellent yields.26 The protocol uses
molecular iodine in catalytic amounts and delivers benzylic
sp3 C–H bond functionalisation/amination. Furthermore,
2-aminobenzyl alcohol could also be converted into the
corresponding products in moderate to good yields.
Funding Information
D.S.D. thanks the University Grant Comission (UGC), New Delhi, India
for providing a Senior Research Fellowship under Basic Science
Research (BSR) scheme [F.25-1/2014-15(BSR)/F.7-227/2009 (BSR),
16th Feb 2015].
)(
Acknowledgment
D.S.D. would like to acknowledge PhD Research Scholar Abhishek R.
Tiwari for his help during the preparation of this manuscript.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2018, 29, A–G

F
D. S. Deshmukh, B. M. Bhanage
Letter
Synlett
Table 3 Synthesis of 2-Arylquinazolines from 2-Aminobenzyl alcohola
I2 (10 mol%),
OH
NH2
O2
R2
N
+
NH2
130 °C, 15 h
N
R2
4
2
3
Entry
1
4
2
Product (3)
Yield (%)b
N
N
N
OH
NH2
NH2
N
N
N
62
2a
2d
4
4
3d′
3e′
2
3
4
64
68
58
4
4
2b
2e
O
3f′
N
N
N
N
N
N
Cl
3g′
NO2
5
6
4
4
2g
2k
49
55
3j′
S
3n′
a Reaction conditions: 4 (0.5 mmol), 2 (1.5 mmol).
b GC yield.
Supporting Information
H.-W.; Chen, B.-H. Tetrahedron 2014, 70, 4038. (g) Jeffrey, J. L.;
Bartlett, E. S.; Sarpong, R. Angew. Chem. Int. Ed. 2013, 52, 2194.
(h) Guo, S.-R.; Pailla, S. K.; Yang, M. Adv. Synth. Catal. 2017, 359,
2. (i) Feng, J.; Lv, M. F.; Lu, G. P.; Cai, C. Org. Chem. Front. 2015, 2,
60. (j) Xue, D.; Long, Y.-Q. J. Org. Chem. 2014, 79, 4727. (k) Yan,
Y.; Zhang, Y.; Zha, Z.; Wang, Z. Org. Lett. 2013, 15, 2274.
Supporting information for this article is available online at
https://doi.org/10.1055/s-0037-1609200.
S
u
p
p
ortioInfgrmoaitn
S
u
p
p
ortiInfogrmoaitn
References and Notes
(2) (a) Cenini, S.; Gallo, E.; Penoni, A.; Ragainia, F.; Tollari, S. Chem.
Commun. 2000, 2265. (b) Lu, H.; Subbarayan, V.; Tao, J.; Zhang,
X. P. Organometallics 2010, 29, 389. (c) Ye, Y.-H.; Zhang, J.;
Wang, G.; Chen, S.-Y.; Yu, X.-Q. Tetrahedron 2011, 67, 4649.
(3) (a) Powell, D. A.; Fan, H. J. Org. Chem. 2010, 75, 2726.
(b) Barman, D. N.; Nicholas, K. M. Eur. J. Org. Chem. 2011, 908.
(c) Ni, Z.; Zhang, Q.; Xiong, T.; Zheng, Y.; Li, Y.; Zhang, H.; Zhang,
J.; Liu, Q. Angew. Chem. Int. Ed. 2012, 51, 1244.
(1) (a) Chen, Z.; Wang, B.; Zhang, J.; Yu, W.; Liu, Z.; Zhang, Y. Org.
Chem. Front. 2015, 2, 169. (b) Gephart, R. T. III.; Warren, T. H.
Organometallics 2012, 31, 7728. (c) Rouquet, G.; Chatani, N.
Angew. Chem. Int. Ed. 2013, 52, 11726. (d) Pandey, G.; Laha, R.;
Singh, D. J. Org. Chem. 2016, 81, 7161. (e) Truong, T.; Nguyen, K.
D.; Doan, S. H.; Phan, N. T. S. Appl. Catal., A 2016, 510, 27.
(f) Tang, D.; Li, X.-L.; Guo, X.; Wu, P.; Li, J.-H.; Wang, K.; Jing,
© Georg Thieme Verlag Stuttgart · New York — Synlett 2018, 29, A–G

G
D. S. Deshmukh, B. M. Bhanage
Letter
Synlett
(4) (a) Nishioka, Y.; Uchida, T.; Katsuki, T. Angew. Chem. Int. Ed.
2013, 52, 1739. (b) Ichinose, M.; Suematsu, H.; Yasutomi, Y.;
Nishioka, Y.; Uchida, T.; Katsuki, T. Angew. Chem. Int. Ed. 2011,
50, 9884. (c) Sun, K.; Sachwani, R.; Richert, K. J.; Driver, T. G. Org.
Lett. 2009, 11, 3598.
(5) (a) Intrieri, D.; Mariani, M.; Caselli, A.; Ragaini, F.; Gallo, E.
Chem. Eur. J. 2012, 18, 10487. (b) Milczek, E.; Boudet, N.; Blakey,
S. Angew. Chem. Int. Ed. 2008, 47, 6825. (c) Zardi, P.; Caselli, A.;
Macchi, P.; Ferretti, F.; Gallo, E. Organometallics 2014, 33, 2210.
(6) Peng, H.; Lin, A.; Zhang, Y.; Jiang, H.; Zhou, J.; Cheng, Y.; Zhu, C.;
Hu, H. ACS Catal. 2012, 2, 163.
(15) Ju, J.; Hua, R.; Sua, J. Tetrahedron 2012, 68, 9364.
(16) (a) Omar, M. A.; Conrad, J.; Beifuss, U. Tetrahedron 2014, 70,
3061. (b) Wang, C.; Li, S.; Liu, H.; Jiang, Y.; Fu, H. J. Org. Chem.
2010, 75, 7936.
(17) Omar, M. A.; Conrad, J.; Beifuss, U. Tetrahedron 2014, 70, 5682.
(18) Malakar, C. C.; Baskakova, A.; Conrad, J.; Beifuss, U. Chem. Eur. J.
2012, 18, 8882.
(19) Wang, H.; Chen, H.; Chen, Y.; Deng, G.-J. Org. Biomol. Chem.
2014, 12, 7792.
(20) Tang, L.; Wang, P.; Fan, Y.; Yang, X.; Wan, C.; Zha, Z. Chem-
CatChem 2016, 8, 3565.
(7) Zhang, M. J. Chem. Res. 2013, 606.
(21) (a) Truong, V. L.; Morrow, M. Tetrahedron Lett. 2010, 51, 758.
(b) Xu, C.; Jia, F.-C.; Zhou, Z.-W.; Zheng, S.-J.; Li, H.; Wu, A.-X.
J. Org. Chem. 2016, 81, 3000. (c) Raut, A. B.; Tiwari, A. R.;
Bhanage, B. M. ChemCatChem 2017, 9, 1292. (d) Yan, Y.; Wang, Z.
Chem. Commun. 2011, 9513.
(22) Zhang, J.; Zhu, D.; Yu, C.; Wan, C.; Wang, Z. Org. Lett. 2010, 12,
2841.
(23) Han, B.; Wang, C.; Han, R.-F.; Yu, W.; Duan, X.-Y.; Fang, R.; Yang,
X.-L. Chem. Commun. 2011, 7818.
(8) (a) Liu, J.; Zhang, H.; Yi, H.; Liu, C.; Lei, A. Sci. China Chem. 2015,
58, 1323. (b) Yang, L.; Shi, X.; Hu, B.-Q.; Wang, L.-X. Asian J. Org.
Chem. 2016, 5, 494. (c) Xue, Q.; Xie, J.; Li, H.; Chenga, Y.; Zhu, C.
Chem. Commun. 2013, 3700. (d) Zhao, D.; Shen, Q.; Li, J.-X. Adv.
Synth. Catal. 2015, 357, 339. (e) Liu, W.; Liu, C.; Zhang, Y.; Sun,
Y.; Abdukadera, A.; Wang, B.; Li, H.; Ma, X.; Zhang, Z. Org.
Biomol. Chem. 2015, 13, 7154. (f) Takeda, Y.; Hayakawa, J.; Yano,
K.; Minakata, S. Chem. Lett. 2012, 41, 1672. (g) Fan, R.; Li, W.; Pu,
D.; Zhang, L. Org. Lett. 2009, 11, 1425.
(9) (a) Zhang, M.; Zhang, A.-Q.; Peng, Y. J. Organomet. Chem. 2013,
723, 224. (b) Tsukano, C. Chem. Pharm. Bull. 2017, 65, 409.
(10) (a) Yusubova, M. S.; Zhdankin, M. S. Resource-Efficient Technolo-
gies 2015, 1, 49. (b) Biswas, A.; Selling, G. S.; Shogren, R. L.;
Willett, J. L.; Buchananand, C. M.; Cheng, H. N. Chem. Today
2009, 27, 33. (c) Yamamoto, Y.; Gridnev, I. D.; Patil, N. T.; Jin, T.
Chem. Commun. 2009, 5075. (d) Liu, D.; Lei, A. Chem. Asian J.
2015, 10, 806. (e) Veisi, H. Curr. Org. Chem. 2011, 15, 2438.
(f) Mphahlele, M. J. Molecules 2009, 14, 5308. (g) Ren, Y.-M.; Cai,
C.; Yang, R.-C. RSC Adv. 2013, 3, 7182. (h) Mphahlele, M. J. Mole-
cules 2009, 14, 4814. (i) Parvatkar, P. T.; Parameswaran, P. S.;
Tilve, S. G. Chem. Eur. J. 2012, 18, 5460.
(24) Gopalaiah, K.; Saini, A.; Devi, A. Org. Biomol. Chem. 2017, 15,
5781.
(25) (a) Nale, D. B.; Bhanage, B. M. Green Chem. 2015, 17, 2480.
(b) Wagh, K. V.; Bhanage, B. M. Green Chem. 2015, 17, 4446.
(c) Tiwari, A. R.; Bhanage, B. M. Green Chem. 2016, 18, 144.
(d) Yedage, S. L.; Bhanage, B. M. Green Chem. 2016, 18, 5635.
(e) Gautam, P.; Dhiman, P.; Polshettiwar, V.; Bhanage, B. M.
Green Chem. 2016, 18, 5890. (f) Gautam, P.; Kathe, P.; Bhanage,
B. M. Green Chem. 2017, 19, 823.
(26) General experimental procedure for the synthesis of 2-
arylquinazolines (3): An oven-dried 25 mL round-bottom flask
was charged with 2-aminobenzaldehyde/2-aminobenzophe-
none (1, 0.5 mmol) or 2-aminobenzyl alcohol (4a, 0.5 mmol)
with benzylamine (2, 1.5 mmol) and molecular iodine (10
mol%). The mixture was then stirred at 130 °C for 3–15 h under
an oxygen atmosphere, and the progress of the reaction was
monitored by TLC. Upon completion, the mixture was cooled to
room temperature and the crude product was purified by
column chromatography.
(11) Tekalea, S. U.; Kauthalea, S. S.; Dakea, S. A.; Sardab, S. R.; Pawar,
R. P. Curr. Org. Chem. 2012, 16, 1485.
(12) (a) Vijaychand, A.; Manjula, S. N.; Bharath, E. N.; Divya, B. Int. J.
Pharma Bio Sci. 2011, 2, 780. (b) Ravez, S.; Castillo-Aguilera, O.;
Depreux, P.; Goossens, L. Expert Opin. Ther. Pat. 2015, 25, 1.
(c) Jafari, E.; Khajouei, M. R.; Hassanzadeh, F.; Hakimelahi, G. H.;
Khodarahmi, G. A. Res. Pharma. Sci. 2016, 11, 1. (d) Khan, I.;
Ibrar, A.; Ahmed, W.; Saeed, A. Eur. J. Med. Chem. 2015, 90, 124.
(e) Ajani, O. O.; Audu, O. Y.; Aderohunmu, D. V.; Owolabi, D. V.;
Olomieja, A. O. Am. J. Drug Discov. Dev. 2017, 7, 1.
(13) (a) Zhang, Z.; Wang, M.; Zhang, C.; Zhang, Z.; Lua, J.; Wang, F.
Chem. Commun. 2015, 9205. (b) Tiwari, A. R.; Bhanage, B. M. Org.
Biomol. Chem. 2016, 14, 10567. (c) Li, C.; An, S.; Zhu, Y.; Zhang,
J.; Kang, Y.; Liu, P.; Wang, Y.; Li, J. RSC Adv. 2014, 4, 49888.
(d) Chen, X.; Chen, T.; Ji, F.; Zhou, Y.; Yin, S.-F. Catal. Sci. Technol.
2015, 5, 2197. (e) Ma, J.; Wan, Y.; Hong, C.; Li, M.; Hu, X.; Mo,
W.; Hu, B.; Sun, N.; Jin, L.; Shen, Z. Eur. J. Org. Chem. 2017, 3335.
(f) Chen, X.; Qi, H.; Wu, S.; Liu, L.; Wen, J.; Li, W.; Guo, F.; Bian,
Y.; Li, J. Heterocycles 2017, 94, 86.
6-Chloro-2-(4-methoxyphenyl)quinazoline (3b)
1
Yellow solid (88%); mp 168–170 °C; H NMR (400 MHz, CDC3):
δ = 9.32 (s, 1 H), 8.54–8.52 (m, 2 H), 7.95 (d, J = 9.0 Hz, 1 H), 7.85
(d, J = 2.1 Hz, 1 H), 7.77 (dd, J = 9.0, 2.3 Hz, 1 H), 7.02 (d,
J =8.4 Hz, 2 H), 3.88 (s, 3 H); 13C NMR (101 MHz, CDCl3):
δ = 162.0, 161.1, 159.4, 149.3, 135.0, 132.2, 130.2, 130.1, 125.8,
123.7, 114.0, 55.4; GCMS (EI, 70 eV): m/z (%) = 270 (100), 255
(24), 227 (14), 192 (10).
2,4-Diphenylquinazoline (3q)
White solid (88%); mp 117–119 °C; H NMR (500 MHz, CDCl3):
1
δ = 8.69 (d, J = 8.1 Hz, 2 H), 8.15 (d, J = 8.4 Hz, 1 H), 8.11 (d,
J = 8.4 Hz, 1 H), 7.89–7.85 (m, 3 H), 7.60–7.58 (m, 3 H), 7.54–
7.47 (m, 4 H); 13C NMR (125 MHz, CDCl3): δ = 168.3, 160.2,
152.0, 138.2, 137.7, 133.5, 130.5, 130.2, 129.9, 129.2, 128.7,
128.5, 127.0, 121.7; GCMS (EI, 70 eV): m/z (%) = 282 (65), 281
(100), 203 (8), 178 (8), 151 (6), 141 (7), 77 (8)
(14) (a) Sarode, S. A.; Jadhav, V. G.; Nagarkar, J. M. Tetrahedron Lett.
2017, 58, 779. (b) Yao, S.; Zhou, K.; Wang, J.; Cao, H.; Yu, L.; Wu,
J.; Qiu, P.; Xu, Q. Green Chem. 2017, 19, 2945. (c) Chen, Z.; Chen,
J.; Liu, M.; Ding, J.; Gao, W.; Huang, X.; Wu, H. J. Org. Chem. 2013,
78, 11342. (d) Chen, M.; Zhang, M.; Xiong, B.; Tan, Z.; Lv, W.;
Jiang, H. Org. Lett. 2014, 16, 6028.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2018, 29, A–G