(Diacetoxyiodo)benzene-Mediated Transition-Metal-Free Amination of C(sp3)-H Bonds Adjacent to Heteroatoms with Azoles: Synthesis of N-Alkylated Azoles

Article abstract of DOI:10.1055/s-0037-1610293

A novel PhI(OAc) ₂ -mediated cross-dehydrogenative coupling reaction of α-C(sp ³)-H bonds adjacent to a hetero atom with various azoles has been developed, which provides an alternative method for constructing C-N bonds with high atom efficiency. This new protocol requires no metal catalyst and it provides ready access to a wide range of N-alkylated azole derivatives in moderate to excellent yields by using commercially available PhI(OAc) ₂ as the sole oxidant. Furthermore, the method is effective on a gram scale, which highlights the practicality of this transformation. The result of radical-captured experiments indicated that the transformation might involve a free-radical pathway.

Full text of DOI:10.1055/s-0037-1610293

SYNLETT
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©
Georg Thieme Verlag Stuttgart · New York
2018, 29, A–E
letter
A
en
Synlett
B. Sun et al.
Letter
(
Diacetoxyiodo)benzene-Mediated Transition-Metal-Free Amina-
3
tion of C(sp )–H Bonds Adjacent to Heteroatoms with Azoles:
Synthesis of N-Alkylated Azoles
Bin Suna
Zhiyang Yanb
Can Jin*b
Weike Su*a,b
Z
Z'
Y
X
PhI(OAc)2 (1.0 equiv)
N
Ar
Y
Z
Z'
N
H
+
Metal-free
High funtionality tolerance
C–N bond
Ar
X
H
a
Collaborative Innovation Center of Yangtze River Delta Region Green
X = N, C
Y = N, C
Z, Z' = C, O,
S, N(Me)CO
25 examples
up to 96% yield
Pharmaceuticals, Zhejiang University of Technology, Hangzhou 310014,
P. R. of China
College of Pharmaceutical Sciences, Zhejiang University of Technology,
b
Hangzhou 310014, P. R. of China
jincan@zjut.edu.cn
pharmlab@zjut.edu.cn
Received: 29.08.2018
Accepted after revision: 04.09.2018
Published online: 01.10.2018
kylated azole derivatives through oxidative C–N coupling
reactions. For example, Li and co-workers reported a novel
and efficient method for the synthesis of azole derivatives
DOI: 10.1055/s-0037-1610293; Art ID: st-2018-w0484-l
6
through iron-catalyzed oxidation of ethers. Subsequently,
Abstract A novel PhI(OAc) -mediated cross-dehydrogenative coupling
reaction of α-C(sp )–H bonds adjacent to a hetero atom with various
azoles has been developed, which provides an alternative method for
constructing C–N bonds with high atom efficiency. This new protocol
requires no metal catalyst and it provides ready access to a wide range
of N-alkylated azole derivatives in moderate to excellent yields by using
2
Aruri and co-workers developed a metal-free method for
the N-alkylation of azoles catalyzed by tetrabutylammoni-
um iodide and tert-butyl hydroperoxide (TBHP) through
3
3
7
the α-C(sp )–H activation of ethers (Scheme 1). Recently,
Lakshman’s group described another Ru-catalyzed method
commercially available PhI(OAc) as the sole oxidant. Furthermore, the
3
2
for the functionalization of C(sp )–H bonds adjacent to oxy-
method is effective on a gram scale, which highlights the practicality of
this transformation. The result of radical-captured experiments indicat-
ed that the transformation might involve a free-radical pathway.
8
gen atoms of ethers with various azoles. Although there
have been many achievements relating to the N-alkylation
of azoles through oxidative coupling reactions, several
drawbacks still remain; for example, these transformations
invariable require reflux temperatures for prolonged peri-
ods and they suffer from the need for large excesses of oxi-
dants such as TBHP or di-tert-butyl peroxide (DTBP). Conse-
quently, the development of environmentally friendly and
Key words diacetoxyiodo benzene, C–H functionalization, C–N bond,
azoles, metal-free, amination
Azoles and their derivatives are widely used in pharma-
ceuticals because of their broad spectrum of biological ac-
tivities, including antimicrobial, antiinfection, antiinflam-
matory, DNA-cleavage, and antitubercular properties.1 In
addition, azole derivatives have also been frequently used
3
highly efficient methods for activating C(sp )–H bonds for
the synthesis of functional azoles is still of great interest.
In the past decade, with the growing demand for the de-
velopment of environmentally conscious synthetic ap-
proaches, hypervalent iodine compounds have been exten-
sively used in C–H functionalization reactions, due to their
low toxicity, environmental friendliness, and ready avail-
2
3
as precursors of N-heterocyclic carbenes and ionic liquids.
The N-alkylation of azoles is the most common method for
the synthesis of azole derivatives because of the large num-
ber of N–H bonds present in azoles. The conventional meth-
od for the alkylation of azoles involves nucleophilic substi-
9
ability. For example, Maruoka’s group developed a novel
4
tution with an electrophile such as an alkyl halide. Howev-
method for the direct esterification of benzylic C–H bonds
of alkylbenzenes by a combination of a hypervalent iodine
compound and visible-light irradiation.10 Here, we report a
transition-metal-free oxidative coupling reaction of a vari-
ety of azoles with ethers, tetrahydrothiophene, or NMP to
give a series of N-alkylated azoles by employing inexpen-
er, this strategy suffers from significant limitations such as
harsh conditions, the need for a strong base, overalkylation,
and a lack of commercially available cyclic ether halides.
Nowadays, direct C–H functionalization through a dehydro-
genative pathway has emerged as an attractive method for
5
constructing C–C or C–X bonds. This versatile strategy
sive PhI(OAc) as the sole an oxidant (Scheme 1).
2
avoids the prefunctionalization of substrates and it has ad-
vantages in terms of atom economy. By applying this proto-
col, much progress has been made in syntheses of N-al-
To begin our study, we chose 1H-benzimidazole (1a)
and isochroman (2a) as model reactants to explore and op-
timize the cross-dehydrogenative reaction. The reaction
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B. Sun et al.
Letter
3
a) Previous research on amination of C(sp )–H bonds
TBHP
3.0–5.0 equiv) R1
R2
(
N
H
X
+
+
ref. 6
ref. 8
FeCl3
R1
R2
H
X
X
N
TBAI/TBHP (3.5 equiv)
X=O
+
H
ref. 7a,b
H
N
TBHP
(3.0 equiv)
R1
R2
R1
R2
X = O, S
N
H
X
RuCl3·3H2O
H
X = N(Me)CO or O
b) This work
X
Z
Z'
Y
Ar
Y
Z
Z'
PhI(OAc)2 (1.0 equiv)
N
+
H
N
H
1
Ar
X
X = N, C
Y = N, C
Z,Z' = C, O, S, N(Me)CO
Scheme 1 Syntheses of N-alkylated azole derivatives
was initially studied with Dess-Martin periodinane (DMP)
as the oxidant in DCE at 80 °C without any metal or addi-
tive. Fortunately, the coupling product 3aa was successfully
obtained, even though the yield was only 65% (Table 1, en-
try 1). Encouraged by this result, we investigated other
commercially available oxidants such as 2-iodoxybenzoic
excellent tolerance to aliphatic cyclic ethers such as tetra-
hydrofuran, tetrahydropyran, 1,4-dioxane, or 1,3-dioxolane,
giving the corresponding coupled products 3ac–af in mod-
Table 1 Screening for Optimal Reaction Conditionsa
acid (IBX), PhI(OAc) , [bis(trifluoroacetoxy)iodo]benzene
N
N
2
(
PIFA), TBHP, DTBP, K S O , and O (entries 2–8), but only
2 2 8 2
N
Oxidant (1.0 equiv)
PhI(OAc) promoted this direct amination (entry 2). Among
O
2
+
O
the various oxidants surveyed, IBX and PIFA proved to be ef-
fective for this transformation, but gave lower yields than
Solvent (1.5 mL), 80 °C
N
H
1a
2a
3aa
PhI(OAc) , whereas the other oxidants were ineffective (en-
2
tries 3–8). Subsequently, various commonly used solvents,
including EtOAc, MeCN, acetone, and CH Cl were exam-
ined, but none of these gave a better result (entries 9–12).
b
Entry
Oxidant
DMP
Solvent
Yield (%)
2
2
1
2
3
4
5
6
7
8
9
DCE
65
Increasing the amount of PhI(OAc) to 1.5 equivalents did
PhI(OAc)2
IBX
DCE
92
2
not increase the yield of 3aa (entry 13), and when the
DCE
60
amount of PhI(OAc) was reduced to 0.5 equivalents, the ex-
2
PIFA
DCE
81
pected decrease in yield was observed (entry 14). Increas-
ing the temperature to 100 °C or decreasing the tempera-
ture to 60 °C led to a decrease in the yield of the coupled
product (entries 15 and 16). On the basis of our screening of
the reaction conditions, we concluded that this oxidative
cross-coupling reaction should be performed in DCE at
TBHP
DTBP
DCE
N.D.
N.D.
N.D.
N.D.
70
DCE
K
2
S
2
O
8
DCE
O2
DCE
PhI(OAc)
PhI(OAc)
PhI(OAc)
PhI(OAc)
PhI(OAc)
PhI(OAc)
PhI(OAc)
PhI(OAc)
2
2
2
2
2
2
2
2
EtOAc
MeCN
acetone
8
0 °C for six hours with PhI(OAc) (1.0 equiv) as an oxidant.
2
10
11
12
75
Next, various sets of experiments were carried out to
59
investigate the scope and limitations of this reaction under
the optimized conditions. First, the success of the direct
amination of isochroman (2a) with 1H-benzimidazole (1a)
prompted us to extend our protocol to other ether deriva-
tives (Scheme 2). The method was found to be applicable to
a wide range of ethers, giving the desired coupled products
in moderate to excellent yields. For example, 1,3-dihydro-
CH
2
Cl
2
82
13c
DCE
DCE
DCE
DCE
91
4d
1
1
46
5e
85
1
6f
55
a
Reaction conditions: 1a (0.5 mmoL), 2a (2.0 mmol), oxidant (0.5 mmol),
2-benzofuran reacted with 1H-benzimidazole (1a) to afford
solvent (2.0 mL), 80 °C, 6 h.
b
product 3ab in 88% yield. Next, the reactions of a range of
cyclic ether derivatives that contained no phenyl moiety
were examined. Gratifyingly, this transformation showed
Isolated yield based on 1a.
PhI(OAc)
PhI(OAc)
At 100 °C.
At 60 °C.
c
2
(1.5 equiv).
2
(0.5 equiv).
d
e
f
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Georg Thieme Verlag Stuttgart · New York — Synlett 2018, 29, A–E

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Synlett
B. Sun et al.
Letter
tive than the primary carbon. In addition, we also attempt-
ed to extend the reaction to cyclohexane as a substrate, but
this failed to give the desired product 3al.
Having examined the scope of the C(sp )–H species, we
then examined the corresponding reactions of a series of
Z
Z'
N
Z
Z'
PhI(OAc)2 (1.0 equiv)
DCE, 80 °C
+
N
3
N
H
H
2
N
1a
3
Z, Z' = O, S, N(Me)CO
azoles with isochroman (2a) as a standard substrate
(
Scheme 3). Various substituted benzimidazoles containing
N
N
N
electron-donating groups, such as 5,6-dimethyl-1H-benz-
imidazole and 5-methoxy-1H-benzimidazole, or those con-
taining electron-withdrawing groups, such as 5-chloro-1H-
benzimidazole and 6-nitro-1H-benzimidazole, participated
in the oxidative coupling reaction with isochroman (2a) to
N
N
N
O
O
O
3aa, 92%
3ab, 88%
3ac, 75%
X
N
N
N
N
Ar
Y
X
O
N
N
N
Y
PhI(OAc)2 (1.0 equiv)
DCE, 80 °C
Ar
+
N
H
1
O
O
O
O
O
2a
O
X = N, C
Y = N, C
3
3
ad, 63%
3ae, 52%
3af, 48%
Cl
N
N
N
N
N
N
N
N
N
O2N
N
N
N
A
O
O
O
O
O
O
O
B
3
ag, 95%
3ah, 81%
3ai(A), 42%, 3ai'(B), 20%
3
3
3
ba, 96%
3ca, 73%
3da, 62%
O
N
N
N
N
N
N
N
N
N
O
N
N
N
O
N
N
S
O
O
3
aj, 71%
3ak, 94%
3al, N.D.
ea, 95%
3fa, 82%
3ga, 46%
Scheme 2 Direct alkylation reactions of 1H-benzimidazole: Reaction
conditions: 1a (0.5 mmoL), 2 (2.0 mmol), PhI(OAc) , (0.5 mmol), DCE
2.0 mL), 80 °C, 6 h.
O2N
N
N
N
2
N
N
N
(
Br
O
O
O
erate to excellent yields. Next, the reactivity of the straight-
chain ether derivatives diethyl ether, dibutyl ether, and 1,4-
diethoxybutane were investigated. All these straight-chain
ethers gave the corresponding C–N coupled products, al-
though the yield decreased markedly with increasing
length of the carbon chain of the ethers. For example, dieth-
yl ether (2g) reacted readily with 1H-benzimidazole (1a) to
give the coupled product 3ag in an excellent yield of 95%,
whereas 1,4-diethoxybutane (2i) gave a mixture of 3ai and
ha, 91%
3ia, 80%
3ja, 85%
N
N
N
N
N
N
N
N
N
O
O
O
3
ai′ in yields of 42% and 20%, respectively. Subsequently,
3ka, 70%
3la, 87%
3ma, 72%
3
other categories of α-C(sp )–H bonds adjacent to a hetero
atom were also investigated for this transformation. Tetra-
hydrothiophene and NMP also underwent the transforma-
tion and gave the corresponding oxidative coupled products
Cl
N
N
N
N
N
N
Cl
N
Cl
N
O
3aj and 3ak in 71% and 94% yield, respectively. It should be
O
pointed out that the regioisomeric product was not ob-
tained from the reaction of NMP with 1H-benzimidazole,
possibly because the secondary carbon might be more reac-
3
na, 71%
3oa, 65%
Scheme 3 Direct amination of isochroman 2a with various azoles.
Reaction conditions: 1 (0.5 mmoL), 2a (2.0 mmol), PhI(OAc) (0.5 mmol),
2
DCE (2.0 mL), 80 °C, 6 h.
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B. Sun et al.
Letter
afford the corresponding C–N adducts 3ba–ea in 62–96%
yield. In addition, 4-phenyl-1H-imidazole also coupled to
give 3fa in 82% yield. Next, we expanded the scope of the
azole substrate to include indazoles and pyrazoles. To our
delight, our reaction protocol was efficient with these
azoles and it provided the corresponding coupled products
N
N
N
O PhI(OAc)2 (1.0 equiv)
(1)
+
O
N
H
BHT (5.0 equiv)
DCE, 80 °C
1a
2a
3
aa , N.D.
3ga–ka in synthetically useful yields of 46–91%. For exam-
N
ple, 5-nitro-1H-indazole, which contains a strongly elec-
tron-withdrawing group, gave 3ia in a remarkably high
yield of 80%. On extending the azole substrate to benzotri-
azole, we obtained the desired C–N coupling product 3la in
an excellent yield of 87%. Finally, we examined the reactivi-
ties of purine, 2-chloropurine, and 2,6-dichloropurine, and
we found that all three were well tolerated under the stan-
dard conditions, affording the oxidative coupled products
N
N
O
N
O
O PhI(OAc)2 (1.0 equiv)
(2)
+
O
N
H
TEMPO (5.0 equiv)
DCE, 80 °C
1a
2a
3
aa, N.D.
4, 45%
N
N
N
O
N
3ma–oa in satisfactory yields.
O TEMPO (5.0 equiv)
DCE, 80 °C
(3)
+
O
To evaluate the potential synthetic utility of this C–N
N
O
H
bond formation strategy, we carried out the reaction 1H-
benzimidazole (1a) and isochroman (2a) on a preparative
scale under the optimized conditions, and we obtained the
desired product 3aa in 88% yield (Scheme 4).
1a
2a
3
aa, N.D.
4, N.D.
N
O
O
PhI(OAc)2 (1.0 equiv)
(4)
N
TEMPO (5.0 equiv)
DCE, 80 °C
O
N
2
a
N
N.D.
O
PhI(OAc)2
O
+
N
H
DCE, 80 °C, 6 h
Scheme 5 Control experiments (N.D. = not detected)
1a (10 mmol)
2a (40 mmol)
3aa (88%)
Scheme 4 Large-scale experiment
On the basis of the above experimental results, we pro-
pose the plausible mechanism for our oxidative C–N cou-
pling reaction that is shown in Scheme 6. Initially, the nitro-
gen-centered radical 6 and the iodine radical 7 are formed
through a substitution reaction of 1H-benzimidazole (1a)
To explore the possible mechanism of our transforma-
tion, we carried out several control experiments, as shown
in Scheme 5. First, the addition of the radical scavenger 2,6-
di-tert-butyl-4-methylphenol (BHT) to the model reaction
system completely inhibited the oxidative coupling reaction
with PhI(OAc) , followed by homolysis of the I–N bond. The
2
resulting N-radical 6 then undergoes α-hydrogen abstrac-
tion with isochroman (2a) to afford the isochroman radical
8 (captured by TEMPO). Next, through further oxidation by
7, radical 8 is transformed into the cationic intermediate 9.
Finally, the desired product 3aa is obtained through a cross-
dehydrogenative coupling reaction of 1a and 9.
(
Scheme 5, Equation 1); however, no BHT–isochroman cou-
pled product was obtained. Next, we observed that the
model reaction was also inhibited by TEMPO, another radi-
cal scavenger and, fortunately, the TEMPO–isochroman
coupled product 4 was obtained as a major product
(Scheme 5, Equation 2). This result tends to confirm that a
In conclusion, we have succeeded in developing a novel
radical process is involved in this transformation. Note that
PhI(OAc) -mediated metal-free method for construction of
2
neither 3aa nor 4 was observed in the absence of PhI(OAc)2
C–N bonds through an oxidative cross-coupling reaction
3
(Scheme 5, Equation 3). Finally, we treated isochroman (2a)
between an α-C(sp )–H bond adjacent to a heteroatom and
11
with PhI(OAc) and TEMPO under the standard conditions
various azoles, without adding any base or additive. This
transformation proved to be effective for the amination of
2
without adding benzimidazole (1a); however, the TEMPO–
isochroman coupled product 4 was not observed (Scheme
3
various C(sp )–H bonds, including those of ethers, tetrahy-
5
, Equation 4). This result suggested that 1H-benzimidazole
drothiophene, and NMP, with a wide range of azoles bear-
ing various functional groups, and it gave the correspond-
ing compounds in moderate to good yields. Owing to its
broad substrate scope and high efficiency, this method
should be of great synthetic potential.
not only acts as a substrate, but also plays an important role
in initiating the radical transformation. A GC/MS experi-
ment showed that PhI is formed during the transformation
(see Supporting Information).
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B. Sun et al.
Letter
OAc
(2) (a) Li, F.; Hu, J. J.; Koh, L. L.; Hor, T. S. A. Dalton Trans. 2010, 39,
I
5231. (b) Huckaba, A. J.; Hollis, T. K.; Howell, T. O.; Valle, H. U.;
AcO
OAc
I
Wu, Y. Organometallics 2013, 32, 63. (c) Gupta, S.; Basu, B.; Das,
S. Tetrahedron 2013, 69, 122.
(3) (a) Kore, R.; Srivastava, R. J. Mol. Catal. A: Chem. 2011, 345, 117.
OAc
I
7
N
N
N
N
N
H
(b) Tsuji, Y.; Ohno, H. RSC Adv. 2012, 2, 11279.
N
6
(
4) (a) Milen, M.; Grün, A.; Bálint, E.; Dancsó, A.; Keglevich, G.
Synth. Commun. 2010, 40, 2291. (b) Shieh, W.-C.; Lozanov, M.;
Repič, O. Tetrahedron Lett. 2003, 44, 6943. (c) Hayat, S.; Atta-ur-
Rahman; Choudhary, M.; Khan, K. M.; Schumann, W.; Bayer, E.
Tetrahedron 2001, 57, 9951.
1a
5
OAc
I
O
O
O
2a
7
(
5) (a) Li, C.-J. Acc. Chem. Res. 2009, 42, 335. (b) Yeung, C. S.; Dong,
M. V. Chem. Rev. 2011, 111, 1215. (c) Cho, S. H.; Kwak, J.; Chang,
S. Chem. Soc. Rev. 2011, 40, 5068. (d) Sun, B.; Wang, Y.; Li, D. Y.;
Jin, C.; Su, W. K. Org. Biomol. Chem. 2018, 16, 2902. (e) Lv, Y.; Li,
Y.; Xiong, T.; Lu, Y.; Liu, Q.; Zhang, Q. Chem. Commun. 2014, 50,
2367. (f) Lv, Y.; Sun, K.; Wang, T.; Li, G.; Pu, W.; Chai, N. N.; Shen,
H.; Wu, Y. RSC Adv. 2015, 5, 72142. (g) Murahashi, S.-i.; Komiya,
N.; Terai, H. Angew. Chem. Int. Ed. 2005, 44, 6931.
N
I
8
9
(
Trapped by TEMPO)
N
+
AcO
H
a
1
(
Detected by GC-MS)
N
N
N
H
N
1a
O
–
H+
(6) Pan, S.; Liu, J.; Li, H.; Wang, Z.; Guo, X.; Li, Z. Org. Lett. 2010, 12,
932.
1
3aa
(
7) (a) Aruri, H.; Singh, U.; Sharma, S.; Gudup, S.; Bhogal, M.;
Kumar, S.; Singh, D.; Gupta, V. K.; Kant, R.; Vishwakarma, R. A.;
Singh, P. P. J. Org. Chem. 2015, 80, 1929. (b) Dian, L.; Wang, S.;
Zhang-Negrerie, D.; Du, Y.; Zhao, K. Chem. Commun. 2014, 50,
Scheme 6 Proposed mechanism of our C–N coupling reaction
1
1738.
Funding Information
(
8) Sing, M. K.; Akula, H. K.; Satishkumar, S.; Stahl, L.; Lakshman, M.
We thank the National Natural Science Foundation of China (Grant
No. 21606202) for financial support. We are also grateful to the Col-
lege of Pharmaceutical Sciences, Zhejiang University of Technology
and the Advanced Research Fund for the Doctoral Program of Zhejiang
K. ACS Catal. 2016, 6, 1921.
(9) (a) Buslov, I.; Hu, X. Adv. Synth. Catal. 2014, 356, 3325. (b) Shu,
X.-Z.; Xia, X.-F.; Yang, Y.-F.; Ji, K.-G.; Liu, X.-Y.; Liang, Y.-M. J. Org.
Chem. 2009, 74, 7464. (c) Shakoor, M. A. A.; Mandal, S. K.;
Sakhuja, R. Eur. J. Org. Chem. 2017, 2596. (d) Wu, Z.; He, Y.; Ma,
C.; Zhou, X.; Liu, X.; Li, Y.; Hu, T.; Wen, P.; Huang, G. Asian J. Org.
Chem. 2016, 5, 724.
Province for their financial help.
N
oaitn
a
l
N
a
ut ra
l
Secince
F
o
u
n
d
oaitn
of
C
h
n
i
a
2(
1
6
0
6
2
0
2)
Supporting Information
(10) Sakamoto, R.; Inada, T.; Selvakumar, S.; Moteki, S. A.; Maruoka,
K. Chem. Commun. 2016, 52, 3758.
(11) 1-(3,4-Dihydro-1H-isochromen-1-yl)-1H-benzimidazole
(3aa; Ref. 6); Typical Procedure
Supporting information for this article is available online at
https://doi.org/10.1055/s-0037-1610293.
S
u
p
p
ortioIgnfrm oaitn
S
u
p
p
ortioIgnfrm oaitn
PhI(OAc) (0.5 mmol) was added to a mixture of 1H-benzimid-
2
azole (1a; 0.5 mmol), isochroman (2a; 2.0 mmol), and DCE (2.0
mL) in a Schlenk tube at r.t. The mixture was stirred at 80 °C for
References and Notes
6
h then cooled. H O (10 mL) was added, and the mixture was
2
(
1) (a) Palmer, P. J.; Trigg, R. B.; Warrington, J. V. J. Med. Chem. 1971,
extracted with CH Cl (3 × 10 mL). The combined organic layer
was dried (Na SO ) and concentrated under reduced pressure.
2
2
14, 248. (b) Rossello, A.; Bertini, S.; Lapucci, A.; Macchia, M.;
2
4
Martinelli, A.; Rapposelli, S.; Herreros, E.; Macchi, B. J. Med.
Chem. 2002, 45, 4903. (c) Di Santo, R.; Tafi, A.; Costi, R.; Botta,
M.; Artico, M.; Corelli, F.; Forte, M.; Caporuscio, F.; Angiolella, L.;
Palamara, A. T. J. Med. Chem. 2005, 48, 5140. (d) Rezaei, Z.;
Khabnadideh, S.; Pakshir, K.; Hossaini, Z.; Amiri, F.; Assadpour,
E. Eur. J. Med. Chem. 2009, 44, 3064. (e) Zhang, H.-Z.; Damu, G. L.
V.; Cai, G.-X.; Zhou, C.-H. Eur. J. Med. Chem. 2013, 64, 329.
The residues were purified by flash column chromatography
(silica gel, hexane–EtOAc) to give a colorless oil; yield: 115 mg
(
92%).
1
H NMR (600 MHz, CDCl ): δ = 7.86–7.83 (m, 1 H), 7.65 (s, 1 H),
3
7
7
4
2
1
1
.48–7.46 (m, 1 H), 7.40 (t, J = 7.2 Hz, 1 H), 7.35–7.31 (m, 3 H),
.27 (t, J = 7.2 Hz, 1 H), 7.09 (d, J = 7.8 Hz, 1 H), 6.94 (s, 1 H),
.02–3.98 (m, 1 H), 3.87–3.83 (m, 1 H), 3.17–3.12 (m, 1 H),
(f) Beena; Kumar, N.; Rohilla, R. K.; Roy, N.; Rawat, D. S. Bioorg.
13
.91–2.87 (m, 1 H). C NMR (150 MHz, CDCl ): δ = 144.2, 142.7,
3
Med. Chem. Lett. 2009, 19, 1396. (g) Dubey, A.; Srivastava, S. K.;
Srivastava, S. D. Bioorg. Med. Chem. Lett. 2011, 21, 569.
35.0, 133.8, 130.3, 129.4, 129.2, 127.1, 127.0, 123.4, 122.8,
+
20.4, 111.1, 80.2, 60.1, 27.7. MS (ESI): m/z = 251.1 [M + H] .
©
Georg Thieme Verlag Stuttgart · New York — Synlett 2018, 29, A–E