H
F. Du et al.
Letter
Synlett
(28) General Information
(br, 1 H), 7.77 (d, J = 8.5 Hz, 1 H), 6.77 (d, J = 1.6 Hz, 1 H), 6.54–
6.51 (dd, J = 8.5, 1.8 Hz, 1 H), 3.46 (br, 1 H), 1.91–1.88 (m, 2 H),
1.68–1.64 (m, 2 H), 1.58–1.55 (m, 1 H), 1.46–1.35 (m, 2 H),
1.30–1.18 (m, 3 H). 13C NMR (101 MHz, DMSO-d6): = 170.0,
151.2, 139.8, 134.1, 114.2, 111.2, 109.1, 49.8, 32.6, 31.1, 25.7,
24.4. For IR and MS data see: Martin, A.; Mesa, M.; Docampo,
M.; Gomez, V.; Pellon, R. Synthetic Commun. 2006, 36, 271.
1-[2-(Allyloxy)phenyl]piperidine (3v): According to the
general procedure A, 3v was obtained as a colorless oil (0.21 g,
75%). 1H NMR (400 MHz, CDCl3): 6.95–6.88 (m, 3 H), 6.86–6.82
(m, 1 H), 6.14–6.04 (m, 1 H), 5.49–5.43 (m, 1 H), 5.28–5.24 (m, 1
H), 4.57–4.55 (m, 2 H), 3.03–2.99 (q, J = 9.9, 5.5 Hz, 4 H), 1.78–
1.72 (m, 4 H), 1.60–1.53 (m, 2 H). 13C NMR (101 MHz, CDCl3):
= 151.4, 143.2, 133.7, 122.3, 121.4, 118.6, 116.6, 113.3, 68.9,
52.3, 26.5, 24.6. For IR and MS data see: Sung, S.; Sale, D.; Brad-
dock, D. C.; Armstrong, A.; Brennan, C.; Davies, R. P. ACS Cataly-
sis 2016, 6, 3965.
5,5,8,8-Tetramethyl-N-(2-nitrophenyl)-5,6,7,8-tetrahy-
dronaphthalen-2-amine (4d): According to the general proce-
dure B, 4d was obtained as yellow solid (0.29 g, 71%). 1H NMR
(400 MHz, CDCl3): = 9.48 (br, 1 H), 8.21–8.19 (dd, J = 8.6, 1.5
Hz, 1 H), 7.36–7.32 (m, 2 H), 7.21–7.19 (dd, J = 8.7, 1.1 Hz, 1 H),
7.18 (d, J = 2.3 Hz, 1 H), 7.06–7.03 (dd, J = 8.4, 2.4 Hz, 1 H), 6.75–
6.71 (m, 1 H), 1.71 (s, 4 H), 1.30 (s, 6 H), 1.28 (s, 6 H). 13C NMR
(101 MHz, CDCl3): = 146.7, 143.7, 142.7, 135.8, 135.6, 132.8,
127.8, 126.7, 122.6, 122.0, 117.0, 116.1, 35.0, 34.9, 34.5, 34.1,
31.9, 31.8. For IR and MS data see: Yan, C.; Yang, L.; Fan, W.;
Qian, S.; Wu, Y. Sichuan Daxue Xuebao, Ziran Kexueban. 2010,
47, 847.
All starting materials, reagents, and solvents were commercially
available and used without further purification. Melting points
were determined with a X-4 apparatus and are uncorrected.
The nuclear magnetic resonance (NMR) spectra were recorded
with a Bruker 400 MHz spectrometer in CDCl3 or DMSO-d6 by
using tetramethylsilane (TMS) as an internal standard. Electro-
spray ionization mass spectrometry (ESI-MS) analyses were
recorded with an Agilent 1100 Series MSD Trap SL (Santa Clara,
CA, USA). The reactions were monitored by thin-layer chroma-
tography (TLC: HG/T2354-92, GF254), and compounds were
visualized on TLC with UV light.
Synthesis of 3a–v; General Procedure A
To a solution of aliphatic amine (1.53 mmol), Cu(OAc)2·H2O
(0.13 mmol), QCT (0.26 mmol), K2CO3 (3.85 mmol) in DMSO (3
mL) were added aryl halides (1.28 mmol). The flask was evacu-
ated and backfilled with argon (3×), and the resulting mixture
was heated in an oil bath with appropriate temperature under
rapid stirring for the indicated time. After the complete con-
sumption of aryl halide as monitored by TLC, the flask was
cooled to r.t. The flask was opened to air, and the reaction
mixture (if the product was acidic, the mixture was acidified)
was extracted with EtOAc (3×10 mL), and the organic layer was
washed with water (2×10 mL) and once with brine (10 mL),
dried with magnesium sulfate and concentrated in vacuo. The
product was purified by column chromatography on silica gel.
Synthesis of 4a–p; General Procedure B
To a solution of aromatic amine (1.53 mmol), Cu(OAc)2·H2O
(0.13 mmol), K2CO3 (3.84 mmol) in DEG (3 mL) were added aryl
halides (1.28 mmol). The flask was evacuated and backfilled
with argon (3×), and the resulting mixture was heated in an oil
bath with appropriate temperature under rapid stirring for the
indicated time. After the complete consumption of aryl halide
as monitored by TLC, the flask was cooled to r.t. The flask was
opened to air, and the reaction mixture (if the product was
acidic, the mixture was acidified) was extracted with EtOAc
(3×10 mL), and the organic layer was washed with water (2×10
mL) and once with brine (10 mL), dried with magnesium sulfate
and concentrated in vacuo. The product was purified by column
chromatography on silica gel.
N-(4-Methoxyphenyl)-2-methyl-3-(trifluoromethyl)aniline
(4j): According to the general procedure B, 4j was obtained as
1
white solid (0.21 g, 58%). H NMR (400 MHz, CDCl3): = 7.18–
7.09 (m, 3 H), 7.00 (br, 2 H), 6.89–6.87 (m, 2 H), 3.81 (s, 3 H),
2.33 (s, 3 H). 13C NMR (101 MHz, CDCl3): = 155.8, 145.1, 135.5,
130.9, 129.9 (J = 29.1 Hz), 128.9, 126.2, 124.7 (J = 274.9 Hz),
123.2, 118.4, 117.2 (J = 6.0 Hz), 114.9, 55.6, 13.2 (J = 2.3 Hz).
HRMS (ESI): m/z [M – H]– calcd for C15H13F3NO: 280.0955;
found: 280.0962. See high-resolution mass spectra in SI.
2-(Allyloxy)-N-phenylaniline (4p): According to the general
procedure B, 4p was obtained as a brown oil (0.23 g, 80%). 1H
NMR (400 MHz, CDCl3): = 7.31–7.25 (m, 3 H), 7.16–7.14 (m, 2
H), 6.96–6.78 (m, 4 H), 6.18 (br, 1 H), 6.14–6.04 (m, 1 H), 5.44–
5.38 (dq, J = 17.2, 3.1, 1.6 Hz, 1 H), 5.32–5.28 (dq, J = 10.5, 2.7,
1.3 Hz, 1 H), 4.61–4.59 (dt, J = 8.9, 1.4 Hz, 2 H). For IR and MS
see: Ding, X.; Huang, M.; Yi, Z.; Du, D.; Zhu, X.; Wan, Y. J. Org.
Chem. 2017, 82, 5416.
2-(Allyloxy)aniline (5aa): According to the general procedure
C, 5aa was obtained as brown oil (0.14 g, 72%). 1H NMR (400
MHz, CDCl3): = 6.81–6.77 (m, 2 H), 6.73–6.67 (m, 2 H), 6.12–
6.03 (m, 1 H), 5.42 (dq, J = 17.2, 3.2, 1.6 Hz, 1 H), 5.26 (dq, J =
10.5, 2.8, 1.4 Hz, 1 H), 4.55 (dt, J = 5.3, 1.5 Hz, 2 H), 3.64 (br, 2 H).
GC-MS: 149 [M]. For IR and MS see: Carmona, R. C.; Koester, O.
D.; Correia, C. R. D. Angew. Chem. Int. Ed. 2018, 5737, 12067.
Characterization data for all known compounds are provided in
the Supporting Information.
Synthesis of 5a–z, 5aa; General Procedure C
A sealed reaction vessel was charged with ammonia (aq, 25%)
(1.8 mL, 12.8 mmol), Cu(OAc)2·H2O (0.13 mmol), QCT (0.26
mmol) in NMP (1.8 mL) and aryl halides (1.28 mmol). The
resulting mixture was heated in an oil bath with appropriate
temperature under rapid stirring for the indicated time. After
complete consumption of the aryl halide as monitored by TLC,
the reaction vessel was cooled to rt. It was opened to air, and the
reaction mixture was extracted with EtOAc (3×10 mL), and the
organic layer was washed with water (2×10 mL) and once with
brine (10 mL), dried with magnesium sulfate and concentrated
in vacuo. The product was purified by column chromatography
on silica gel.
4-Chloro-2-(cyclohexylamino)benzoic acid (3o): According to
the general procedure A, 3o was obtained as a white solid (0.28
g, 87%). Mp 173–176 °C. 1H NMR (400 MHz, DMSO-d6): = 8.04
© 2019. Thieme. All rights reserved. Synlett 2019, 30, A–H