Transition metal-free direct amination of benzoxazoles using formamides as nitrogen sources

Article abstract of DOI:10.1016/j.tetlet.2014.02.070

A transition metal-free method for the direct amination of benzoxazoles using formamides as nitrogen sources is reported, which was mediated by an inexpensive and environmentally friendly tetrabutylammonium iodide/tert-butyl hydroperoxide system and gave the 2-aminobenzoxazole derivatives with moderate to good yields.

Full text of DOI:10.1016/j.tetlet.2014.02.070

Tetrahedron Letters 55 (2014) 2233–2237
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Transition metal-free direct amination of benzoxazoles using
formamides as nitrogen sources
⇑
Rui Wang , Hong Liu, Liang Yue, Xiao-ke Zhang, Qiu-yuan Tan, Ruo-lin Pan
School of Pharmacy & Bioengineering, Chongqing University of Technology, Chongqing 400054, China
a r t i c l e i n f o
a b s t r a c t
Article history:
A transition metal-free method for the direct amination of benzoxazoles using formamides as nitrogen
sources is reported, which was mediated by an inexpensive and environmentally friendly tetrabutylam-
monium iodide/tert-butyl hydroperoxide system and gave the 2-aminobenzoxazole derivatives with
moderate to good yields.
Received 24 September 2013
Revised 9 February 2014
Accepted 20 February 2014
Available online 28 February 2014
Ó 2014 Elsevier Ltd. All rights reserved.
Keywords:
Benzoxazoles
Transition metal-free
Amination
Formamides
Nitrogen-centered radicals
An immense effort has been made to develop efficient strategies
for the construction of CAN bonds of heteroaromatic compounds
through the activation of CAH bonds.1 During the recent years,
remarkable progresses have been made in the amination of
benzoxazoles which are important units for the synthesis of phar-
maceuticals, natural products, functional materials, and many
other biologically active molecules.2 In particular, site-selective
amination of azoles through CAH bond activation was recently
developed.3 Despite these significant advances, developing
environmentally benign and economical syntheses is an area of re-
search that is being vigorously pursued, direct installation of amino
groups or their surrogates on aryl CAH bonds remains a challenge
under transition metal-free conditions. Formamides are cheap,
commercially available and thus can be potentially used as the
ideal amination reagents.4 In 2009, Chang et al. reported a stoichi-
ometric amount of silver catalyzed direct amination using forma-
mides as an amino group source.3a Recently, groups of Li and Yu
independently disclosed Cu and Fe-catalyzed direct oxidative
C–H amination of benzoxazoles with formamide derivatives
(Scheme 1, path a, b, and c).3g,h However, using transition metal
catalysts renders these methods increasingly unattractive and
environmentally less friendly. At the present stage, C–H amination
of benzoxazoles under metal-free conditions using formamides as
nitrogen sources is unrevealed. If a synthetic method that allows
Previous work
a) Ag2CO3 (2 eq)
O
O
R2
N
N
O
b) Cu(OAc)2 (0.2 eq)
R2
N
R1
R1
+
H
H
N
R3
O2,130 °C
c) FeCl3 (0.25 eq)
O
R3
Design of this work
N
R2
N
O
Transition metal-free
d)
R2
N
R3
R1
R1
+
N
R3
O
Scheme 1. Comparison of previous works with this work.
the direct use of normally ‘unreactive’ formamides as nitrogen
sources were to become available under transition-metal free con-
ditions other than those procedures mediated by transition metal,
a practical and environmentally friendly synthetic approach in
direct amination of benzoxazoles would be opened.
A recent report by Wan suggested that nitrogen radicals can
participate in TBAI (tetrabutylammonium iodide)-catalyzed acyla-
tion reactions.5 Inspired by this transformation, we envisioned that
aminyl radicals with persistent radical effect could react with acti-
vated benzoxazoles in situ, which would obviate the need of tran-
sition metal.6 Herein, we describe a new procedure for the
oxidative amination of benzoxazoles using formamides as nitrogen
sources under transition metal-free conditions (Scheme 1, path d).
To optimize the amination protocol, we extensively screened
various experimental parameters. Initially, benzoxazole (1a) and
N,N-dimethylformamide (DMF) were chosen as model substrates
⇑
Corresponding author. Tel./fax: +86 23 6256 3182.
E-mail address: wangrx1022@163.com (R. Wang).
http://dx.doi.org/10.1016/j.tetlet.2014.02.070
0040-4039/Ó 2014 Elsevier Ltd. All rights reserved.

2234
R. Wang et al. / Tetrahedron Letters 55 (2014) 2233–2237
Table 1
Screening conditionsa
O
O
N
O
N
Transition metal-free
N
H
+
H
N
1a
2a
3a
Entry
TBAI (mol %)
[O] (equiv)
Additive (equiv)
DMF (equiv)
Yieldb (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
147
15
16c
17d
18e
19f
20g
20
20
20
20
20
10
20
40
20
20
20
20
20
20
20 (I2)
20
20
20
20
20
TBHP (5)
TBHP (5)
—
15
15
15
15
10
15
15
15
15
15
15
15
15
15
15
15
15
15
15
45
20
42:58:73
80
80
76
70
38
51
46
Trace
Trace
Trace
Trace
22
<5
Trace
43
AcOH (1.5:3:5)
AcOH (5)
AcOH (5)
AcOH (5)
AcOH (5)
AcOH (10)
AcOH (5)
PhCOOH (5)
TFA (3)
TfOH (3)
PTSA (3)
AcOH (5)
AcOH (5)
AcOH (5)
AcOH (5)
AcOH (5)
AcOH (5)
AcOH(5)
AcOH (5)
TBHP (10)
TBHP (12)
TBHP (10)
TBHP (10)
TBHP (10)
TBHP (10)
TBHP (10)
TBHP (10)
TBHP (10)
TBHP (10)
H2O2 (10)
UHP (10)
TBHP (10)
TBHP (10)
TBHP (10)
TBHP (10)
TBHP (10)
TBHP (10)
<5
<10
<10
a
Reaction conditions: A mixture of benzoxazole (1a, 1 mmol), DMF, Bu4NI, TBHP (70% aqueous solution) and acid additive was stirred in solvent (3.0 mL) at 90 °C for
reaction, The given equivalents (equiv) are related to 1a.
b
Isolated yield after column chromatography.
Reaction was carried out in dioxane, acetonitrile, dichloromethane, ethyl acetate and DMF, respectively. AcOH = acetic acid, DCE = 1,2-dichloroethane, TFA = trifluoro-
c–g
acetic acid, TfOH = trifluoromethanesulfonic acid, PTSA = p-toluenesulfonic acid.
(Table 1). Fortunately, we were pleased to observe that the desired
product (3a) was obtained albeit in low yield when a TBAI catalyst
(20 mol %) was used in the presence of tert-butyl hydroperoxide
(TBHP) under an air atmosphere (Table 1, entry 1). Encouraged
by this result, we decided to screen the reaction conditions.
Gratifyingly, increasing the amount of AcOH resulted in high yields
indicating the significance of the acid additive in the reaction
(Table 1, entry 2). The reaction yields could be further improved
to 80% when 10 equiv of TBHP was employed (Table 1, entries 3
and 4), while decreasing the amount of DMF or catalyst resulted
in low yields (Table 1, entries 5 and 6). Particularly notable, exces-
sive amounts of catalyst or additive caused the decomposition of
raw material and led to a dramatically decreased conversion
(Table 1, entries 7 and 8). Furthermore, various additives were
investigated, compared to AcOH, PhCOOH was less effective,
whereas strong acid such as TFA, TfOH, or PTSA were completely
ineffective additives (Table 1, entries 9–12). Alteration TBHP with
H2O2 was proved to be less effective, although increasing the
concentration of H2O2 afforded slightly higher yield, due probably
to H2O2 poorer tendency to the formation of nitrogen-centered
radicals than TBHP (Table 1, entries 13 and 14). When iodine was
employed instead of our catalytic system, the corresponding reac-
tion proceeded sluggishly presumably attributed to their poorer
capability to promote the formation of aminyl radical than TBAI
(Table 1, entry 14). We then surveyed the effect of different sol-
vents: the reactions proceeded with low yields in dioxane, acetoni-
trile, EtOAc, DCM, and DMF (Table 1, entries 15–19), DCE was an
adequate choice of solvent for the reaction to achieve a high yield.
Under these optimized conditions (Table 1, entry 3), the scope
of this reaction with different formamides was investigated. The
N,N-disubstituted formamides such as N,N-diethylformamide,
N,N-dipropylformamide reacted smoothly, furnishing moderate
yields (Table 2, entries 2 and 3). However, substrate N,N-diisopro-
pylformamide did not give the desired product, perhaps as a result
of steric hindrance (Table 2, entry 4). Furthermore, we screened
cyclic formamides such as 1-formylpyrrolidine, 1-formylpiperidine
and 4-formylmorpholine that provided the highest yield of desired
products (Table 2, entries 5–7). Interestingly, the N-monosubsti-
tuted formamides could be also converted to the corresponding
2-aminobenzoxazoles in moderate yield under our reaction condi-
tions, it was observed that N-methylformamide gave synthetically
acceptable yield (Table 2, entry 8). In addition, N-cyclopentylfor-
mamide and N-cyclohexylformamide offered an appreciable yield
of the desired product (Table 2, entries 9 and 10). Notably, N-
unsubstituted formamides were completely ineffective substrate
(Table 2, entry 11).
Regarding the benzoxazole moiety, several functional groups
including electron-donating (methyl, methoxy, phenyl, and tert-
butyl) and electron-withdrawing (chloro, bromo, and nitro) sub-
stituents were tolerated well (Table 2, entries 12–22). It is note-
worthy that halo-substituted benzoxazoles were compatible
under standard conditions, thus leading to halo-substituted prod-
ucts, which could be used for further transformations (Table 2, en-
tries 17–19). The position of the substituents on the phenyl ring of
benzoxazoles affected the reaction yield slightly. Interestingly, a
reaction with 5-nitrobenzoxazole (Table 2, entry 20) afforded the
corresponding product with a slightly lower yield which was
proved to be an ineffective substrate in FeCl3-catalyzed direct
amination.3h In the case of electronic nature of the aromatic
motifs, such as 5-phenylbenzoxazole, containing electron-donating
substituent, increased yields of products were obtained
(Table 2, entries 14–16, 21 and 22), the effect is the reverse with
electron-withdrawing substituents and transformed into the de-
sired products in synthetically acceptable yields (Table 2, entries
17–20). It is worth noting that 5-methylbenzoxazole gave only
72% yield (Table 2, entry 11), which was less effective when com-
pared to the approach mediated by Ag2CO3 or FeCl3 that probably
attributed to the benzylic CAH bond oxidation of the substrate

R. Wang et al. / Tetrahedron Letters 55 (2014) 2233–2237
2235
Table 2
Table 2 (continued)
Synthesis of various 2-aminobenzoxazolesa
Entry
Product
Yieldb (%)
20 mol %TBAI
O
O
N
O
N
O
N
R2
R3
aq TBHP
R2
N
O
22
3v
86
47
R1
R1
N
+
H
N
R3
DCE, AcOH, 90 °C
tBu
1
2
3
S
N
N
23
3w
Entry
1
Product
Yieldb (%)
80
O
NR = no reaction.
a
N
N
Reaction conditions: benzoxazole (1.0 mmol), formamide (15 mmol), TBAI (0.2
equiv), TBHP (70% aq solution, 10 mmol) and acetic acid (2.0 equiv) in 1,2-dichlo-
roethane (3.0 mL) at 90 °C for 12 h, also see Ref.14
3a
3b
N
O
b
2
3
39
35
Isolated yield.
N
N
O
under standard conditions.8 Additionally, when benzothiazole was
subjected to the standard reaction conditions, 2-aminobenzothia-
zole was selectively obtained in modest yield (Table 2, entry 23).
Encouraged by the aforementioned direct CAN bond formation of
benzoxazoles, we extended the method to direct amination of
benzimidazole, 1-methylbenzimidazole, 1,5,6-trimethylbenzimi-
dazole, and 1,3,4-oxadiazoles by using formamides as the nitrogen
sources. Disappointingly, the amination did not occur under stan-
dard reaction conditions. Additionally, when we treated indole
derivatives (1 mmol, such as indole, 1-methylindole, 1,7-dimethyl-
indole, or 1,4-dimethylindole) with DMF (15 equiv) in AcOH (3 mL)
at 90 °C in the presence of TBAI (0.2 equiv), and TBHP (10 equiv) for
12 h, we were delighted to find that the starting materials-indole
derivatives were consumed completely, but LC–MS and NMR anal-
ysis unveiled that the oxidant products-indole-2,3-dione deriva-
tives were formed.9
N
3c
O
N
N
4
3d
Trace
N
O
5
6
7
8
3e
3f
70
73
79
28
N
O
N
N
O
N
O
3g
3h
N
O
NH
N
To gain an insight into the reaction mechanism, the following
control experiments were performed under the standard reaction
conditions (Scheme 2). Firstly, ammonium hypoiodite ([Bu4N]+[-
IO]ꢀ) or iodite ([Bu4N]+[IO2]ꢀ), which should be generated in situ
from Bu4NOH and iodine, was not the active species (Scheme 2,
Eq. a).10 Secondly, when stoichiometric amount of hypervalent
iodine reagent (such as ICl) was employed instead of our catalytic
system, no desired product was obtained (Scheme 2, Eq. b). This
result indicates that the reaction pathway is not followed in catal-
ysis involving in situ generated hypervalent iodine or I2–I+ redox
process.8,11 Moreover, switching the catalyst to KI provided the
desired product 3a in 74% isolated yield (Scheme 2, Eq. c). On the
other hand, when the radical scavenger TEMPO (2,2,6,6-tetrameth-
ylpiperidine-N-oxyl) was added to the reaction system, the reac-
tion was inhibited (Scheme 2, Eq. d), which implies that the
reaction presumably proceed via a radical intermediate.
O
N
9
3i
3j
63
71
NH
O
10
NH
NH2
N
N
O
11
12
13
3k
3l
NR
72
68
N
O
N
O
N
O
3m
N
N
N
14
15
16
17
18
19
3n
3o
3p
3q
3r
87
82
76
62
48
68
N
O
On the basis of the above results and previous reports,12 a plau-
sible mechanism for this reaction is illustrated in Scheme 3. Our
Ph
N
O
Me O
MeO
O
N
N
O
N
O
Bu4NOH (20 mol %)
a)
N
+
N
I2 (20 mol %)
TBHP (10 equiv)
90 °C, 12 h
H
N
N
N.R
O
O
N
O
Cl
Cl
O
O
O
O
N
ICl (1 equiv)
b)
c)
d)
N
+
+
H
H
H
N
N
N
TBHP (10 equ iv)
90 °C, 12 h
N
N
N
N
O
N.R
O
O
N
KI (20 mol %)
3s
N
TBHP (10 equiv)
90 °C, 12 h
N
N
Br
74 % yield
O
N
O
N
O
20
21
3t
34
84
TEMPO (1 equiv)
N
N
N
not observed
O2N
MeO
+
TBAI (20 mol %)
TBHP (10 equiv)
90 °C, 12 h
O
N
O
3u
N
Scheme 2. Investigation of the reaction mechanism.

2236
R. Wang et al. / Tetrahedron Letters 55 (2014) 2233–2237
Wang, D.-H.; Yu, J.-Q. Angew. Chem., Int. Ed. 2009, 48, 5094; (i) Ackermann, L.;
HO-
+
tBuO
1/2I2
tBuOOH HO
tBuOOH
Vicente, R.; Kapdi, A. R. Angew. Chem., Int. Ed. 2009, 48, 9792; (j) Lyons, T. W.;
Sanford, M. S. Chem. Rev. 2010, 110, 1147; (k) Dudnik, A. S.; Gevorgyan, V.
Angew. Chem., Int. Ed. 2010, 49, 2096; (l) Satoh, T.; Miura, M. Synthesis 2010,
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2012, 45, 788.
I-
-
+
H2O + tBuOO
H
N
H
N+
R1
N
-OAc
HRA
TBHP
AcOH
N
R2
H
2. For selected examples, see: (a) Malamas, M. S.; Manas, E. S.; McDevitt, R. E.;
Gunawan, I.; Xu, Z. B.; Collini, M. D.; Miller, C. P.; Dinh, T.; Henderson, R. A.;
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O
O
O
+
R1
N
N
D
1
B
tBuOH
tBuO
O
R2 tBuO
H
O
C
tBuOOH
tBuOO
tBuOO
ET
N
A
R1
R1
R2
H
N
PT
2
tBuOH
tBuO
R2
R1
N
R2
N
tBuOOH
tBuOO
+
tBuO
O
3
N
O
tBuOO
N
tBuOH
tBuOOH
O
tBuOH
E
tBuOOH
Scheme 3. A plausible mechanism for this amination.
proposed mechanism for this transformation can be divided into
the radical addition and radical coupling pathway. The tert-butoxyl
and tert-butylperoxyl radicals which formed by the promotion of
TBAI through I2–Iꢀ redox process abstract hydrogen from the form-
amide to generate aminyl radical A.5 For the radical addition case
the radical A can react as with a reactive intermediate B, leading
to provide radical cation C. Oxidation of an radical intermediate
C can occur by electron transfer (ET) and proton transfer (PT) to
give protonated 2-aminobenzoxazole D. This result does not ex-
clude an alternative pathway, which involves CAH bond cleaving
hydrogen radical abstraction (HRA) as a single-step transformation
to provide the same intermediate D, which may be converted into
the final product 3. Alternatively, the final product can be produced
via the radical coupling pathway of the aminyl radical A and benz-
oxazole radical E, since when benzoxazole or N-formylmorpholine
reacted, respectively, under the standard conditions the radical
coupling precursor ions of [M+H]+ at m/z 237 and 173 could be
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In summary, we have described the first example of a high effi-
cient, straightforward and TBAI/TBHP mediated method for benz-
oxazoles amination under transition metal-free conditions using
formamides as nitrogen sources. Transition-metal free and forma-
mides as nitrogen sources make this transformation practical and
environmentally friendly. Further studies to break through the lim-
itation of benzothiazoles are ongoing in our group.
Acknowledgments
We are grateful to the National Natural Science Foundation of
China (31170747), Scientific and Technological Research Program
of Chongqing Municipal Education Commission of China (No.
KJ130811) for financial support.
9. The amination of indole, see: (a) Li, Y. X.; Wang, H. X.; Ali, S.; Xia, X. F.; Liang, Y.
M. Chem. Commun. 2012, 2343; (b) Liu, X. Y.; Gao, P.; Shen, Y. W.; Liang, Y. M.
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Supplementary data
10. (a) Uyanik, M.; Okamoto, H.; Yasui, T.; Ishihara, K. Science 2010, 328, 1376; (b)
Feng, J.; Liang, S.; Chen, S. Y.; Zhang, J.; Fu, S. S.; Yu, X. Q. Adv. Synth. Catal. 2012,
354, 1287.
Supplementary data associated with this article can be found,
in the online version, at http://dx.doi.org/10.1016/j.tetlet.2014.
02.070. These data include MOL files and InChiKeys of the most
important compounds described in this article.
11. For I2–I+ redox process, see: (a) Yan, Y. Z.; Wang, Z. Y. Chem. Commun. 2011,
9513. and Ref. 7; for I2–Iꢀ redox process, see:; (b) Chen, L.; Shi, E.; Liu, Z. J.;
Chen, S. L.; Wei, W.; Lei, H.; Xu, K.; Wan, X. B. Chem. Eur. J. 2011, 17, 4085. and
ref. 5.
12. (a) Froehr, T.; Sindlinger, C. P.; Kloeckner, U.; Finkbeiner, P.; Nachtsheim, B. J.
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References and notes
13. MS data were recorded on Finnigan LCQDECA ion-trap mass spectrometer (San
Jose, CA, USA) with electrospray ionization sources operated in positive ion
mode. 2,20-Bibenzoxazole m/z at 237, 4,40-bimorpholine m/z at 173, and 1,2-
dimorpholinoethane-1,2-dione m/z at 229 could be detected.
1. For recent reviews, see: (a) Alberico, D.; Scott, M. E.; Lautens, M. Chem. Rev.
2007, 107, 174; (b) Satoh, T.; Miura, M. Chem. Lett. 2007, 36, 200; (c) Seregin, I.
V.; Gevorgyan, V. Chem. Soc. Rev. 2007, 36, 1173; (d) Park, Y. J.; Park, J.-W.; Jun,
C.-H. Acc. Chem. Res. 2008, 41, 222; (e) Lewis, J. C.; Bergman, R. G.; Ellman, J. A.
Acc. Chem. Res. 2008, 41, 1013; (f) Kakiuchi, F.; Kochi, T. Synthesis 2008, 3013;
(g) Kulkarni, A. A.; Daugulis, O. Synthesis 2009, 4087; (h) Chen, X.; Engle, K. M.;
14. General experimental procedure: Benzoxazole (1.0 mmol), N,N-disubstituted
formamide (15 mmol), TBAI (0.2 equiv/74 mg), TBHP (70% aqueous solution,
10 mmol/1.37 mL), and acetic acid (5.0 equiv) in 1,2-dichloroethane (3.0 mL)

R. Wang et al. / Tetrahedron Letters 55 (2014) 2233–2237
2237
were added to a reaction vessel in air. The reaction mixture was heated in an
oil bath at 90 °C for 12 h. After completion of the reaction, the mixture was
quenched by addition of a saturated solution of sodium disulfite (4.0 mL, for
(400 MHz, CDCl3, ppm): d = 7.37 (d, J = 7.8 Hz, 1H), 7.24 (d, J = 8.0 Hz, 1H),
7.17–7.13 (m, 1H), 7.03–7.00 (m, 1H), 4.99 (d, J = 7.2 Hz, 1H), 3.78–3.73 (m,
1H), 2.16–2.12 (m, 2H), 1.80–1.76 (m, 2H), 1.72–1.64 (m, 1H), 1.50–1.42 (m,
2H), 1.34–1.21 (m, 3H); 13C NMR (100 MHz, CDCl3) d = 161.2, 148.2, 143.0,
123.6, 120.4, 116.0, 108.4, 51.8, 33.3, 25.3, 24.6. ESI-HRMS m/z calcd for
[C13H16N2O + H]+: 217.1341, found 217.1337. Compound 3l: petroleum ether/
ethyl acetate 5:1; slight white solid (yield 72%); 1HNMR (400 MHz, CDCl3,
ppm): d = 7.14 (s, 1H), 7.11 (d, J = 7.8 Hz, 1H), 6.79 (d, J = 8.4 Hz, 1H), 3.18 (s,
6H), 2.38 (s, 3H); 13C NMR (100 MHz, CDCl3) d = 163.3, 147.3, 143.7, 133.5,
120.8, 116.4, 107.9, 37.7, 21.5. ESI-HRMS m/z calcd for [C10H12N2O + H]+:
177.1028, found 177.1032. Compound 3o: petroleum ether/ethyl acetate 5:1;
slight white solid (yield 82%); 1HNMR (400 MHz, CDCl3, ppm): d = 7.12 (d,
J = 8.8 Hz, 1H), 6.93 (d, J = 2.0 Hz, 1H), 6.56 (dd, J1 = 8.4 Hz, J2 = 2.4 Hz, 1H), 3.80
(s, 3H), 3.17 (s, 3H); 13C NMR (100 MHz, CDCl3) d = 163.3, 156.5, 144.1, 143.1,
107.9, 106.1, 100.7, 55.4, 37.1. ESI-HRMS m/z calcd for [C10H12N2O2 + H]+:
193.0977, found 193.0970. Compound 3q: petroleum ether/ethyl acetate 5:1;
slight yellow solid (yield 62%); 1H NMR (400 MHz, CDCl3, ppm): d = 7.29 (s,
1H), 7.13 (d, J = 8.4 Hz, 1H), 6.95 (d, J = 8.4 Hz, 1H), 3.19 (s, 6H); 13C NMR
(100 MHz, CDCl3) d = 163.8, 147.7, 145.0, 129.2, 120.0, 116.1, 109.1, 37.7. ESI-
HRMS m/z calcd for [C9H9ClN2O + H]+: 197.0482, found 197.0486.
removal of excess TBHP) and
a saturated solution of sodium hydrogen
carbonate (4.0 mL). Then the mixture was extracted with ethyl acetate
(3 ꢁ 15 mL), combined organic phases were dried over anhydrous Na2SO4
and the organic solvent was removed under vacuum. The crude residue was
purified by chromatography on
a silica gel column affording the desired
product. Analytical data for some representative compounds: Compound 3a:
petroleum ether/ethyl acetate 5:1; yellow solid (yield 80%); 1HNMR (400 MHz,
CDCl3, ppm): d = 7.35 (d, J = 7.2 Hz, 1H), 7.24 (d, J = 6.0 Hz, 1H), 7.15–1.13 (m,
1H), 7.00–6.97 (m, 1H), 3.19 (s, 6H); 13C NMR (100 MHz, CDCl3) d = 163.1,
149.1, 143.6, 123.9, 120.2, 116.0, 108.6, 37.7. ESI-HRMS m/z calcd for
[C9H10N2O + H]+: 163.0871, found 163.0865. Compound 3f: petroleum ether/
ethyl acetate 4:1; yellow solid (yield 73%); 1HNMR (400 MHz, CDCl3, ppm):
d = 7.35 (d, J = 8.0 Hz, 1H), 7.24 (d, J = 8.0 Hz, 1H),7.16 (t, J = 7.6 Hz, 1H), 7.01 (t,
J = 7.6 Hz, 1H), 3.86 (m, 4H), 1.69 (br s, 6H); 13C NMR (100 MHz, CDCl3)
d = 162.0, 148.2, 142.9, 123.4, 119.8, 115.5, 108.1, 46.1, 24.8, 23.6. ESI-HRMS m/
z
calcd. For [C12H14N2O + H]+: 203.1184, found 202.1179. Compound 3j:
petroleum ether/ethyl acetate 4:1; yellow solid (yield 71%); 1HNMR