Elemental Sulfur-Promoted Aerobic Dehydrogenative Aromatization of Cyclohexanones with Amines

Article abstract of DOI:10.1021/acs.joc.0c01122

An elemental sulfur-promoted aerobic dehydrogenation system for the access to N,N′-dialkyl-o-phenylenediamines and N-substituted 2-naphthylamines is reported herein. Readily available cyclohexanones and amines (especially alkylamines) are transformed smoo

Full text of DOI:10.1021/acs.joc.0c01122

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Note
Elemental Sulfur-Promoted Aerobic Dehydrogenative
Aromatization of Cyclohexanones with Amines
Zhen Wang, Cheng Li, Huawen Huang, and Guo-Jun Deng
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.0c01122 • Publication Date (Web): 24 Jun 2020
Downloaded from pubs.acs.org on June 25, 2020
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Elemental Sulfur-Promoted Aerobic Dehydrogenative
Aromatization of Cyclohexanones with Amines
Zhen Wang‡, Cheng Li‡, Huawen Huang*, Guo-Jun Deng*
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Key Laboratory for Green Organic Synthesis and Application of Hunan Province, Key Laboratory of
Environmentally Friendly Chemistry and Application of Ministry of Education, College of Chemistry,
Xiangtan University, Xiangtan 411105, China. E-mail: hwhuang@xtu.edu.cn; gjdeng@xtu.edu.cn
‡ These authors contributed equally to this work.
NHR'
NHR'
O
R' NH2
R
R
S (1.0 equiv)
or
or
CyH/Py, 110 oC, 24 h
O2 (sealed tube)
O
NHR'
Abstract: An elemental sulfur-promoted aerobic dehydrogenation system for the
access to N,N'-dialkyl-o-phenylenediamines and N-substituted 2-naphthylamines is
reported herein. Readily available cyclohexanones and amines (especially
alkylamines) are transformed smoothly into target products. Aromatic amines can be
achieved from all aliphatic reagents under aerobic metal-free reaction conditions.
Control reactions show that the combinational use of elemental sulfur and molecular
oxygen is exceptionally essential for this dehydrogenative aromatizaiton.
Arylamines are core structural motifs widely used in pharmaceutical development and
materials synthesis.1 Thus great efforts have been made to pursue efficient access to
arylamines for decades.2 Notablely, N,N'-dialkyl-o-phenylenediamines, as a subclass
of arylamines, have emerged as varied building blocks in the synthesis of catalysts
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and ligands. For example, the diamine-coordinated arsenic(III) complex A, formed
from N,N’-diisopropylbenzene diamine, showed good catalytic activity for the
hydroboration of aldehydes in a recent report (Figure 1, A).3 Moreover, a series of
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N-heterocyclic
carbene
(NHC),
which
are
derivatives
of
N,N'-dialkyl-o-phenylenediamines, have been developed and applied as ligands or
catalysts in molecular synthesis (Figure 1, B).4-8 Owing to the significant application
values of these arylamines, their synthesis has grabbed considerable interest.
alkyl
i-Pr
alkyl
NH
Bn
As O
N
N
X
N
N
NH
i-Pr
catalyst for
hydroboration
alkyl
precursors of N-
heterocyclic carbenes
alkyl
(A)
(B)
Figure 1. Valuable derivatives from N,N'-dialkyl-o-phenylenediamines.
Traditional Buchwald-Hartwig amination9 and Ullmann-type amination10 remain
the most common tools to synthesize N,N'-dsubstituted-o-phenylenediamines
(Scheme 1a). However, these methods have obvious limitations. First, such reactions
usually require the use of highly functionalized aromatic substrates (such as
benzene-1,2-diamines), thus greatly limiting the substrate scope. Second, excessive
additives such as bases and transition-metal catalysts are usually required. Moreover,
in order to achieve the alkylation or arylation of both amino groups, it is usually
necessary to use excessive reactant, which may lead to overalkylation or arylation.
Therefore, selectivity control is crucial for this kind of reaction. As proven superior
aryl sources to traditional highly functionalized arenes, cyclohexanones provide a
viable access to diverse aromatic products with high value added through
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dehydro-aromatization, such as aromatic amines and diamines.11 In most cases,
transition-metal catalysts such as palladium were employed for this kind of
trnasformation.12 In 2018, Pan’s group reported an iodine-catalysis for the synthsis of
N,N’-diaryl-o-phenylenediamines from cyclohexanones and anilines, in which
alkylamines proved unreactive.13 In the same year, our group also developed
elemental sulfur-promoted aerobic C-N bond construction14 to access a series of
o-arylenediamines through aromatization of cyclohexanones (Scheme 1b).14a In that
system, however, aliphatic amines featured low but promising reactivity. Since the
use of cyclohexanones as aryl source could provide efficient approaches for the
preparation of arylamines, it is highly desirable to find a proper reaction system that is
capable for amination with broader substrate scope including aliphatic amines. Within
our ongoing research program on sustainable chemistry,15 herein, we report a new
elemental sulfur-promoted aerobic dehydrogenation coupling/aromatization of
cyclohexanones with aliphatic/aromatic amines under metal-free conditions (Scheme
1c). Hence, a range of N,N'-dialkyl-o-phenylenediamines have been achieved from all
non-aromatic reagents. Besides, the coupling of β-tetralone instead of cyclohexanones
afforded the major 2-naphthylamine products.
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Scheme 1. Synthetic Strategies for Substituted Aromatic (Di)Amines
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(a) Traditional synthesis of substituted o-phenylenediamines
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H
X
N
R1
R1
[Pd], [Cu] or [base]
coupling
partners
Ar
Ar
+
X
N
H
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X = NH2 or halo
excess bases & highly functional arenes
(b) Synthesis of aromatic (di)amines from cyclohexanones
H2N R'
H
H
N
N
R'
R'
+
R'
[Pd] or I2
I2 or S
O
N
R
R
R
H
limited to aromatic amines
(c) This work: sulfur-promoted aerobic dehydrogenation strategy
H2N R'
R'
H
N
+
O
NH
S
S
R'
R
O2
O2
NH
R'
R
15 examples
yield up to 83%
metal-free & simple reagents
alkylamines are tolerated
15 examples
yield up to 78%
To investigate the optimal reaction conditions, we selected cyclohexanone (1a) and
cyclohexylamine (2a) as the model substrates (Table 1). When the mixture in the
absence of sulfur powder was heated in cyclohexane for 24 hours under oxygen
atmosphere, only trace amounts of target product 3a could be detected by GC-MS
(entry 1). Then sulfur powder was added to obtain desired product 3a in 31% yield
(entry 2). Subsequently, various solvents including toluene, chlorobenzene, pyridine
and 1,4-dioxane have been screened, and the separation yields were all enhance to
moderate (entries 3-6). Of them, pyridine gave the best result (entry 5). Then we
examined mixed solvent (entries 7-9). To our delight, the yield of the reaction was
significantly increased to 82% when cyclohexane and pyridine (1:1) were used as
co-solvent (entry 7). While the yield dramatically declined when the reaction was
conducted at 100 oC (entry 10), elevating the reaction temperature to 120 oC furnished
almost the same yield (entry 11). Decreasing the amount of sulfur powder to 50 mol%
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reduced the yield to 44% (entry 12). In contrast, the reaction yield was not improved
when the amount of sulfur powder was increased to 1.5 equiv. (entry 13). Notably,
molecular oxygen is critical in this kind of reaction since only trace amounts of
product were obtained when the reaction was carried out under air atmosphere (entry
14).
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Table 1. Optimization of Reaction Conditionsa
O
NH2
NH
conditions
+
2
N
H
1a
2a
3a
entry
S (equiv.) solvent
yield
(%)b
trace
31
1
0
cyclohexane (CyH)
CyH
2
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
0.5
1.5
1.0
3
toluene
54
4
chlorobenzene
pyridine (Py)
1,4-dioxane
CyH/Py (1:1)
CyH/Py (1:2)
CyH/Py (2:1)
CyH/Py (1:1)
CyH/Py (1:1)
CyH/Py (1:1)
CyH/Py (1:1)
CyH/Py (1:1)
60
5
68
6
59
7
82
8
72
9
66
10c
11d
12
13
14e
49
80
44
82
trace
a Reaction conditions: 1a (0.2 mmol), 2a (0.7 mmol), S (1 equiv.), solvent (0.6 mL), stirred at 110
oC under O2 for 24 h. b Isolated yield. c 100 oC. d 120 oC. e Under air.
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With the optimized reaction conditions in hand, we then investigated the scope of
substrates in this reaction system (Table 2). When the reaction was conducted on a 10
mmol scale, the yield of 3a was 48%. The reaction of 4-phenylcyclohexan-1-one and
cyclohexanamine generated 3b in 83% yield. When isopropylamine reacted with
4-phenylcyclohexan-1-one, 3c was obtained in 32% yield. The target products were
obtained in good yields when other α-branched aliphatic amines were used (3d and
3e). Next, the scope of cyclohexanones was explored under similar reaction
conditions. When cyclohexanone and para-alkyl cyclohexanones were employed in
this reaction, the corresponding products were afforded in moderate to good yields
(3f-3m). Unfortunately, the existences of an electron withdrawing group (such as
ester group, 3n) in cyclohexanone prohibited the transformation and resulted in the
corresponding product in very low yield, which may be attributed to the low stability
of imine intermediate with an electron-withdrawing group. When
1,2-diaminocyclohexane was treated under standard conditions, the target product (3o)
was obtained in 53% yield. Interestingly, the reaction of cyclohexanone with
benzene-1,2-diamine generated the cyclized product 3p as major product without
dehydro-aromatization of cyclohexanone moiety.
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Table 2. Synthesis of N,N'-dialkyl-o-phenylenediaminesa
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O
NHR'
NHR'
S (1.0 equiv)
+
2
R' NH2
CyH/Py, 110 oC, 24 h
O2 (sealed tube)
R
R
1
2
3
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NH
NH
NH
NH
Ph
N
H
Ph
N
H
N
Ph
N
H
H
b
3c
3d
3b
, 81%
, 83%
, 32%
3a
, 82% (48%)
NH
NH
NH
NH
N
H
Ph
N
H
Et
N
H
, 54%
N
H
3g
3h
, 65%
3e
3f
, 57%
, 75%
NH
NH
NH
NH
N
H
N
H
n-Pr
N
H
t-Bu
N
H
3l
, 67%
3k
3j
, 70%
, 81%
3i
, 52%
H
N
NH
NH
N
N
EtO2C
N
H
Ph
N
H
Ph
N
H
c
c
3m
3n
, 0%
, 78%
3o
3p
, 37%
, 53%
NHtBu
NHtBu
, trace
NHCH2CH2Ph
NHCH2CH2Ph
NHPh
NHPh
3s
, 28%
3r
3q
, 18%
a Conditions: 1 (0.2 mmol), 2 (0.7 mmol), S (1.0 equiv.), pyridine/cyclohexane (1:1, 0.6 mL), 110
oC, 24 h, O2. Isolated yields based on 1. b 10 mmol scale. c 2 (0.35 mmol).
Unfortunately, primary aliphatic amines featured very low reactivity in the present
system (3q, 18% yield), therein the major side product was determined to be
tetrahydrobenzo[d]imidazole.14c As with tertiary aliphatic amines such as t-BuNH2,
the possible influence of strong steric hindrance prohibited the ortho
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difunctionalization (3r). Compared with our previous sulfur/BzOH-promoted aerobic
reaction with aromatic amines,14a the present acid-free system was also not
approvingly effective for the aromatized diamination of cyclohexanones with anilines
(3s, 28% yield), thus revealing the uniqueness of both diamination systems.
In order to further extend the application of this reaction system, a range of
amines were tested to react with β-tetralone, which exclusively afforded
monoaminative naphthalen-2-amine products (Table 3). Aliphatic amines afforded the
target products (5a-5d) in moderate to good yields with high selectivity. What’s more,
the 5 mmol scale reaction afforded 5d in 43% yield. Besides aliphatic amines, aniline
was also reactive in this transformation and afforded desired product (5e) in 63%
yield. When a cyano group was located at the ortho-position of aniline, 5f was
obtained in low yield whereas a moderate yield could be achieved when para-cyano
aniline was used (5o). Furthermore, moderate yields were given by meta-methyl
aniline (5g) and para-trifluoromethyl aniline (5n). Generally, methoxy, halogens,
trifluoromethoxy and ester group were all tolerated under the standard conditions to
give the desired diarylamine products in moderate yields (5h-5m). In the present
system, α-tetralone (3,4-dihydronaphthalen-1(2H)-one) was not a suitable substrate
for either diamination or monoamination.
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Table 3. Synthesis of N-substituted 2-Naphthylaminesa
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H
O
N
S (1.0 equiv)
R'
R' NH2
+
CyH/Py, 110 oC, 24 h
O2 (sealed tube)
4a
2
5
H
N
H
H
N
Ph
N
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5b
, 65%
5a
5d
, 76%
5c
, 78%
H
N
5e
R = H, , 63%
5k
R = 4-Br, , 55%
5f
R = 2-CN, , 33%
5l
R = 4-OCF3, , 42%
b
5g
R = 3-Me, , 63%
, 71% (43%)
5m
R = 4-CO2Me,
, 55%
5h
H
N
R = 4-OMe, , 46%
5n
R = 4-CF3, , 69%
5i
R = 4-F, , 38%
5o
R = 4-CN, , 65%
R
5j
R = 4-Cl, , 46%
a Conditions: 4a (0.4 mmol), 2 (0.2 mmol), S (1 equiv.), pyridine/cyclohexane (1:1, 0.6 mL), 110
oC, 24 h, O2. b 5 mmol scale.
To get mechanistic insight upon the current sulfur-mediated aerobic diamination,
some control experiments were carried out. When radical inhibitor such as BHT or
TEMPO was added into the reaction system, the reaction yield of 3h was not
significantly affected (Scheme 2a). As a possible intermediate alternative,
cyclohexane-1,2-dione was treated under the standard conditions and the yield of 3h
was obtained in 58%.14 The reaction was completely prohibited in argon atmosphere
and much lower yield was achieved in the absence of elemental sulfur. These results
revealed that both oxygen and elemental sulfur are indispensable in the terminal
dehydroaromatization process (Scheme 2b). Furthermore, the condensation
intermediate, which was formed in situ, of β-tetralone and cyclopentamine smoothly
generated mono-amination product 5c in 78% yield under this dehydrogenation
system (Scheme 2c). This means the reaction selectivity control is closely related with
the type of cyclohexanone substrate. On the basis of experimental results and our
previous observations,14a a possible reaction mechanism was proposed (Scheme 2d).
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The transformation is initiated through the condensation of cyclohexanone 1a and
cyclohexanamine 2a to afford enamine intermediate I. Subsequently,
Willgerodt-Kindler-type sulfuration of I with elemental sulfur occurs to give
α-sulfurated ketimine II, with nucleophilic substitution with the second
cyclohexanamine followed by dehydrogenative aromatization via aerobic oxidation to
furnish the final product 3a. We suspect that the increased alkalinity of aliphatic
amines that led to low reactivity of them in our previous acidic system with anilines.
In present system, we used a enhanced alkaline system with pyridine that may
promote the condensation. Comparably, the enamine intermediate was formed from
2-tetralone and amines that favor direct aromatization to afford the mono-amination
products.
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Scheme 2. Control Experiments and Mechanistic Proposal
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O
NH2
6
7
8
9
standard conditions
NH
(a)
2
+
radical inhibitor (1.5 eq.)
N
H
3h
3h
BHT / TEMPO ---- (yield of , 42% / 54%)
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O
NH2
O
+
[O]
NH
NH
(b)
2
- 2H2O
N
H
N
H
3h
3h
standard conditions / under Ar / without S ---- (yield of , 58% / 0% / <10%)
O
H
H
N
N
[O]
(c)
+
- H2O
NH2
5c
5c
standard conditions / under Ar / without S ---- (yield of , 78% / trace / <10%)
Cy
Cy
O
NH
NH
Cy NH2
Cy NH2
Sn
2a
2a
Sn
(d)
Willgerodt-Kindler
Sn-1 & H2S
O2
II
I
1a
Sn & H2O
Cy
Cy
Cy
Cy
N
NH
N
NH
H
H
H
N
N
N
N
O2
O2
Cy
Cy
Cy
Cy
III
IV
3a
In summary, we have developed an elemental sulfur-promoted aerobic
dehydrogenative access to N,N'-dialkyl-o-phenylenediamines and N-substituted
2-naphthylamines from readily available cyclohexanone analogues and amines. The
combination use of elemental sulfur and oxygen could efficiently promote this kind of
transformation. When aliphatic amines were used as the amination reagents, the
corresponding bis-amination products N,N'-dialkyl-o-phenylenediamines were
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selectively generated from all non-aromatic substrates under metal-free conditions.
This reaction system complements well to our previous aromatized bis-amination of
cyclohexanones with aromatic amines, and also provides an effective metal-free
alternative for the preparation of N-substituted 2-naphthylamines through
dehydrogenative aromatization.
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EXPERIMENTAL SECTION
General information. All reactions were carried out under an atmosphere of oxygen
unless otherwise noted. Column chromatography was performed using silica gel
1
13
(200-300 mesh). H NMR and C NMR spectra were recorded on Bruker-AV (400
and 100 MHz, respectively) instrument using Chloroform-d or acetone-d6 as solvent
and TMS as an internal standard. Mass spectra were measured on Agilent 5975
GC-MS instrument (EI). High-resolution mass spectra (ESI) were obtained with the
Thermo Scientific LTQ Orbitrap XL mass spectrometer. The structures of known
1
compounds were further corroborated by comparing their H NMR, 13C NMR data
and MS data with those of literature. Reagents were used as received or prepared by
our laboratory.
General procedure for the synthesis of diamines (3). A 10 mL reaction vessel was
charged with cyclohexanone (1a, 21 μL, 0.2 mmol), cyclohexanamine (2a, 80 μL, 0.7
mmol), S8 (6.4 mg, 12.5 mol %), pyridine/cyclohexane (1:1, 0.6 mL) under O2. The
o
mixture was heated in an oil bath at 110 C for 24 h. After cooling to room
temperature, the volatiles were removed under reduced pressure. The residue was
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to give the desired product 3a as red oil, 44.6 mg, yield 82%.
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10 mmol scale reaction of 3a. A 50 mL round bottom flask was charged with
cyclohexanone (1a, 1.05 mL, 10 mmol), cyclohexanamine (2a, 4.00 mL, 35 mmol),
S8 (0.32 g, 6.25 mmol), pyridine/cyclohexane (1:1, 15 mL). The reaction vessel was
purged with oxygen for three times and connected with a condenser pipe and an
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o
oxygen balloon. The mixture was heated in an oil bath at 110 C for 24 h. After
cooling to room temperature, the volatiles were removed under reduced pressure. The
residue was purified by column chromatography on silica gel (petroleum ether/ethyl
acetate = 50:1) to give the desired product 3a as red oil, 1.31 g, yield 48%.
General procedure for the synthesis of naphthylamines (5). A 10 mL reaction
vessel was charged with β-tetralone (4a, 54 μL, 0.4 mmol), cyclohexanamine (2a, 23
μL, 0.2 mmol), S8 (6.4 mg, 12.5 mol %), pyridine/ cyclohexane (1:1, 0.6 mL) under
o
O2. The mixture was heated in an oil bath at 110 C for 24 h. After cooling to room
temperature, the volatiles were removed under reduced pressure. The residue was
purified by column chromatography on silica gel (petroleum ether/ethyl acetate =
100:1) to give the desired product 5d as yellow oil, 31.9 mg, yield 71%.
5 mmol scale reaction of 5d: A 50 mL round bottom flask was charged with
β-tetralone (4a, 675 μL, 2.5 mmol), cyclohexanamine (2a, 2.00 mL, 17.5 mmol), S8
(0.16 g, 3.125 mmol), pyridine/cyclohexane (1:1, 10 mL). The reaction vessel was
purged with oxygen for three times and connected with a condenser pipe and an
o
oxygen balloon. The mixture was heated in an oil bath at 110 C for 24 h. After
cooling to room temperature, the volatiles were removed under reduced pressure. The
residue was purified by column chromatography on silica gel (petroleum ether/ethyl
acetate = 50:1) to give the desired product 5d as yellow oil, 453.6 mg, yield 43%.
N1,N2-Dicyclohexylbenzene-1,2-diamine (3a, CAS: 24464-62-8).16 1H NMR (400
MHz, Chloroform-d) δ 6.78−6.66 (m, 4H), 3.20−3.13 (m, 2H), 2.07−2.00 (m, 4H),
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1.79−1.72 (m, 4H), 1.67−1.62 (m, 2H), 1.39−1.31 (m, 4H), 1.28−1.16 (m, 6H);
13C{1H} NMR (100 MHz, Chloroform-d) δ 136.5, 118.9, 113.6, 52.1, 33.6, 26.0, 25.0;
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HRMS calcd. for: C18H29N2 (M+H)+ 273.2325, found 273.2329.
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N3,N4-Dicyclohexyl-[1,1'-biphenyl]-3,4-diamine (3b). 4-Phenylcyclohexan-1-one
(34.8 mg, 0.2 mmol) and cyclohexanamine (80 μL, 0.7 mmol) were used as the
substrates under the given reaction conditions. The residue was purified by column
chromatography (silica gel, petroleum ether/ethyl acetate = 100:1) to give 3b as green
oil, 57.8 mg, yield 83%. 1H NMR (400 MHz, Acetone-d6) δ 7.58−7.52 (m, 2H), 7.36
(t, J = 7.7 Hz, 2H), 7.21 (t, J = 7.4 Hz, 1H), 6.93 (d, J = 6.7 Hz, 2H), 6.70 (d, J = 8.7
Hz, 1H), 3.83 (s, 2H), 3.36−3.23 (m, 2H), 2.11−2.04 (m, 4H), 1.79−1.72 (m, 4H),
1.67−1.60 (m, 2H), 1.46−1.19 (m, 10H); 13C{1H} NMR (100 MHz, Acetone-d6) δ
143.3, 137.4, 137.3, 131.6, 129.5, 127.1, 126.6, 117.9, 117.9, 113.6, 112.7, 52.9, 52.8,
+
34.3, 34.3, 27.0, 26.9, 25.9; HRMS (ESI) m/z calcd for C24H33N2 (M+H)+ 349.2638,
found 349.2642.
N3,N4-Diisopropyl-[1,1'-biphenyl]-3,4-diamine (3c). 4-Phenylcyclohexan-1-one
(34.8 mg, 0.2 mmol) and isopropylamine (60 μL, 0.7 mmol) were used as the
substrates under the given reaction conditions. The residue was purified by column
chromatography (silica gel, petroleum ether/ethyl acetate = 100:1) to give 3c as
yellow solid, 17.1 mg, yield 32%. Mp: 62−64 oC. 1H NMR (400 MHz, Acetone-d6) δ
7.60−7.54 (m, 2H), 7.38−7.34 (m, 2H), 7.23−7.18 (m, 1H), 6.99−6.91 (m, 2H), 6.68
(d, J = 8.0 Hz, 1H), 4.01−3.70 (m, 2H), 3.70−3.59 (m, 2H), 1.21 (t, J = 6.0 Hz, 12H);
13C{1H} NMR (100 MHz, Acetone-d6) δ 143.3, 137.5, 137.4, 131.6, 129.5, 127.1,
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126.7, 117.8, 113.3, 112.2, 45.1, 45.0, 23.4; HRMS calcd. for: C18H25N2 (M+H)+
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269.2012, found 269.2015.
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N3,N4-Di-sec-butyl-[1,1'-biphenyl]-3,4-diamine (3d). 4-Phenylcyclohexan-1-one
(34.8 mg, 0.2 mmol) and sec-butylamine (70 μL, 0.7 mmol) were used as the
substrates under the given reaction conditions. The residue was purified by column
chromatography (silica gel, petroleum ether/ethyl acetate = 100:1) to give 3d as red
oil, 47.9 mg, yield 81%. 1H NMR (400 MHz, Acetone-d6) δ 7.59−7.53 (m, 2H), 7.37
(t, J = 7.7 Hz, 2H), 7.21 (t, J = 7.4 Hz, 1H), 6.99−6.87 (m, 2H), 6.69 (d, J = 8.0 Hz,
1H), 3.80 (d, J = 32.6 Hz, 2H), 3.49−3.39 (m, 2H), 1.70−1.60 (m, 2H), 1.56−1.46 (m,
2H), 1.22−1.16 (m, 6H), 1.01−0.96 (m, 6H); 13C{1H} NMR (100 MHz, Acetone-d6) δ
143.2, 137.6, 137.5, 131.4, 129.4, 127.0, 126.8, 117.7, 113.4, 112.4, 50.9, 50.9, 50.9,
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+
50.8, 20.6, 10.9, 10.9; HRMS calcd. for: calcd for C20H29N2 (M+H)+ 297.2325,
found 297.2329.
N3,N4-Di(pentan-3-yl)-[1,1'-biphenyl]-3,4-diamine (3e). 4-Phenylcyclohexan-1-one
(34.8 mg, 0.2 mmol) and 3-aminopentane (81 μL, 0.7 mmol) were used as the
substrate under the given reaction conditions. The residue was purified by column
chromatography (silica gel, petroleum ether/ethyl acetate = 100:1) to give 3e as red oil,
1
45.4 mg, yield 75%. H NMR (400 MHz, Acetone-d6) δ 7.59−7.54 (m, 2H),
7.38−7.33 (m, 2H), 7.23−7.18 (m, 1H), 6.92−6.94 (m, 2H), 6.70−6.65 (m, 1H), 3.83
(d, J = 25.2 Hz, 2H), 3.35−3.26 (m, 2H), 1.66−1.50 (m, 8H), 0.98−0.93 (m, 12H);
13C{1H} NMR (100 MHz, Acetone-d6) δ 143.3, 137.8, 131.3, 129.5, 128.4, 127.0,
+
126.6, 117.7, 113.4, 112.5, 56.7, 56.6, 27.5, 27.4, 10.7; HRMS calcd. for: C22H33N2
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(M+H)+ 325.2638, found 325.2641.
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N1,N2-Dicyclopentylbenzene-1,2-diamine (3f). Cyclohexanone (21 μL, 0.2 mmol)
and cyclopentanamine (68 μL, 0.7 mmol) were used as the substrates under the given
reaction conditions. The residue was purified by column chromatography (silica gel,
petroleum ether/ethyl acetate = 100:1) to give 3f as brown oil, 27.9 mg, yield 57%. 1H
NMR (400 MHz, Chloroform-d) δ 6.78−6.75 (m, 2H), 6.71−6.68 (m, 2H), 3.76 (p, J =
6.0 Hz, 2H), 2.07−1.99 (m, 4H), 1.76−1.73 (m, 4H), 1.64−1.59 (m, 4H), 1.55−1.49 (m,
4H); 13C{1H} NMR (100 MHz, Chloroform-d) δ 137.1, 118.7, 112.4, 54.7, 33.7, 24.4;
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+
HRMS calcd. for: C16H25N2 (M+H)+ 245.2012, found 245.2012.
N1,N2-Dicyclopentyl-4-methylbenzene-1,2-diamine (3g). 4-Methylcyclohexan-1-one
(25 μL, 0.2 mmol) and cyclopentanamine (68 μL, 0.7 mmol) were used as the
substrates under the given reaction conditions. The residue was purified by column
chromatography (silica gel, petroleum ether/ethyl acetate = 100:1) to give 3g as
brown oil, 33.6 mg, yield 65%. 1H NMR (400 MHz, Chloroform-d) δ 6.60 (d, J = 7.8
Hz, 1H), 6.54 (d, J = 8.0 Hz, 1H), 6.49 (s, 1H), 3.79−3.69 (m, 2H), 2.79 (s, 2H), 2.27
(s, 3H), 2.07−1.96 (m, 4H), 1.74−1.70 (m, 4H), 1.64−1.58 (m, 4H), 1.54−1.48 (m,
13
4H); C{1H} NMR (100 MHz, Chloroform-d) δ 137.9, 134.3, 128.6, 118.5, 113.4,
+
113.2, 55.2, 54.8, 33.8, 33.7, 24.4, 21.2; HRMS calcd. for: C17H27N2 (M+H)+
259.2169, found 259.2169.
N1,N2-Dicyclopentyl-4-ethylbenzene-1,2-diamine (3h). 4-Ethylcyclohexan-1-one (28
μL, 0.2 mmol) and cyclopentanamine (68 μL, 0.7 mmol) were used as the substrates
under the given reaction conditions. The residue was purified by column
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chromatography (silica gel, petroleum ether/ethyl acetate = 100:1) to give 3h as red
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oil, 29.4 mg, yield 54%. H NMR (400 MHz, Chloroform-d) δ 6.63 (d, J = 7.9 Hz,
8
9
1H), 6.60−6.54 (m, 1H), 6.53 (s, 1H), 3.78−3.70 (m, 2H), 2.56 (q, J = 7.6 Hz, 2H),
2.07−1.98 (m, 4H), 1.77−1.70 (m, 4H), 1.64−1.58 (m, 4H), 1.55−1.49 (m, 4H), 1.21 (t,
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J = 7.6 Hz, 3H); C{1H} NMR (100 MHz, Chloroform-d) δ 137.7, 135.1, 134.6,
117.2, 113.1, 112.1, 55.1, 54.7, 33.7, 28.6, 24.3, 24.3, 16.0; HRMS calcd. for:
+
C18H29N2 (M+H)+ 273.2325, found 273.2329.
N1,N2-Dicyclopentyl-4-propylbenzene-1,2-diamine (3i). 4-Propylcyclohexan-1-one
(31 μL, 0.2 mmol) and cyclopentanamine (68 μL, 0.7 mmol) were used as the
substrates under the given reaction conditions. The residue was purified by column
chromatography (silica gel, petroleum ether/ethyl acetate = 100:1) to give 3i as brown
1
oil, 29.8 mg, yield 52%. H NMR (400 MHz, Chloroform-d) δ 6.61 (d, J = 7.9 Hz,
1H), 6.56 (d, J = 8.1 Hz, 1H), 6.51 (s, 1H), 3.79−3.69 (m, 2H), 2.95 (s, 2H), 2.49 (t, J
= 7.7 Hz, 2H), 2.07−1.96 (m, 4H), 1.77−1.70 (m, 4H), 1.66−1.58 (m, 6H), 1.54−1.46
(m, 4H), 0.94 (t, J = 7.3 Hz, 3H); 13C{1H} NMR (100 MHz, Chloroform-d) δ 137.5,
134.5, 133.6, 118.0, 113.1, 112.7, 55.1, 54.7, 37.9, 33.7, 25.0, 24.3, 14.0; HRMS
+
calcd. for: C19H31N2 (M+H)+ 287.2482, found 287.2486.
4-(tert-Butyl)-N1,N2-dicyclopentylbenzene-1,2-diamine
(3j).
4-(tert-Butyl)cyclohexan-1-one (30.8 mg, 0.2 mmol) and cyclopentanamine (68 μL,
0.7 mmol) were used as the substrates under the given reaction conditions. The
residue was purified by column chromatography (silica gel, petroleum ether/ethyl
1
acetate = 100:1) to give 3j as green oil, 48.6 mg, yield 81%. H NMR (400 MHz,
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Acetone-d6) δ 6.68 (d, J = 2.1 Hz, 1H), 6.64 (dd, J = 8.1, 2.1 Hz, 1H), 6.53 (d, J = 8.1
Hz, 1H), 3.84−3.72 (m, 2H), 2.91 (s, 2H), 2.02−1.92 (m, 4H), 1.75−1.67 (m, 4H),
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13
1.62−1.47 (m, 8H), 1.26 (s, 9H); C{1H} NMR (100 MHz, Acetone-d6) δ 141.4,
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137.7, 135.5, 115.0, 112.7, 110.5, 55.8, 55.6, 34.6, 34.2, 34.2, 32.1, 25.0, 25.0;
+
HRMS calcd. for: C20H33N2 (M+H)+ 301.2638, found 301.2640.
N1,N2-Dicyclopentyl-4-(tert-pentyl)benzene-1,2-diamine
(3k).
4-(tert-Pentyl)cyclohexan-1-one (38 μL, 0.2 mmol) and cyclopentanamine (68 μL, 0.7
mmol) were used as the substrates under the given reaction conditions. The residue
was purified by column chromatography (silica gel, petroleum ether/ethyl acetate =
1
100:1) to give 3k as green oil, 44.6 mg, yield 70%. H NMR (400 MHz,
Chloroform-d) δ 6.70 (d, J = 7.9 Hz, 1H), 6.66 (s, 1H), 6.62 (d, J = 8.1 Hz, 1H),
3.79−3.72 (m, 2H), 2.86 (s, 2H), 2.08−1.97 (m, 4H), 1.75−1.73 (m , 4H), 1.64−1.57
(m, 6H), 1.51 (s, 4H), 1.25 (s, 6H), 0.71 (t, J = 7.4 Hz, 3H); 13C{1H} NMR (100 MHz,
Chloroform-d) δ 139.9, 136.7, 134.6, 115.8, 112.1, 110.8, 55.0, 54.8, 37.3, 37.0, 33.8,
+
33.7, 28.6, 24.4, 24.4, 9.3; HRMS calcd. for: C21H35N2 (M+H)+ 315.2795, found
315.2797.
N1,N2-Dicyclopentyl-4-pentylbenzene-1,2-diamine (3l). 4-Pentylcyclohexan-1-one
(38 μL, 0.2 mmol) and cyclopentanamine (68 μL, 0.7 mmol) were used as the
substrates under the given reaction conditions. The residue was purified by column
chromatography (silica gel, petroleum ether/ethyl acetate = 100:1) to give 3l as brown
1
oil, 42.1 mg, yield 67%. H NMR (400 MHz, Chloroform-d) δ 6.61 (d, J = 7.8 Hz,
1H), 6.55 (d, J = 7.9 Hz, 1H), 6.50 (s, 1H), 3.79−3.69 (m, 2H), 3.10 (s, 2H),
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2.54−2.48 (m, 2H), 2.07−1.96 (m, 4H), 1.78−1.70 (m, 4H), 1.66−1.56 (m, 6H),
1.51−1.48 (m, 4H), 1.34−1.31 (m, 4H), 0.89 (t, J = 6.8 Hz, 3H); 13C{1H} NMR (100
MHz, Chloroform-d) δ 137.5, 134.6, 133.7, 117.9, 113.0, 112.6, 55.1, 54.7, 35.8, 33.7,
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+
31.7, 24.3, 22.6, 14.1; HRMS calcd. for: C21H35N2 (M+H)+ 315.2795, found
315.2800.
N3,N4-Dicyclopentyl-[1,1'-biphenyl]-3,4-diamine (3m). 4-Phenylcyclohexan-1-one
(34.8 mg, 0.2 mmol) and cyclopentanamine (68 μL, 0.7 mmol) were used as the
substrates under the given reaction conditions. The residue was purified by column
chromatography (silica gel, petroleum ether/ethyl acetate = 100:1) to give 3m as
green oil, 50.1 mg, yield 78%. 1H NMR (400 MHz, Acetone-d6) δ 7.57 (d, J = 7.2 Hz,
2H), 7.37 (t, J = 7.6 Hz, 2H), 7.23−7.19 (m, 1H), 6.92 (s, 2H), 6.69 (d, J = 6.4 Hz,
1H), 3.88 (d, J = 29.1 Hz, 2H), 2.10−1.99 (m, 4H), 1.78−1.53 (m, 14H); C{1H}
13
NMR (100 MHz, Acetone-d6) δ 143.6, 137.9, 137.6, 129.5, 127.1, 127.0, 126.6, 117.5,
112.6, 111.3, 55.6, 34.2, 25.1, 25.0; HRMS calcd. for: C22H29N2 (M+H)+ 321.2325,
+
found 321.2327.
7-Phenyl-1,2,3,4,4a,5,10,10a-octahydrophenazine (3o).17 4-Phenylcyclohexan-1-one
(34.8 mg, 0.2 mmol) and 1,2-diaminocyclohexane (43 μL, 0.35 mmol) were used as
the substrate under the given reaction conditions. The residue was purified by column
chromatography (silica gel, petroleum ether/ethyl acetate = 20:1) to give 3n as yellow
o
1
solid, 28.1 mg, yield 53%. Mp: 155−158 C H NMR (400 MHz, Chloroform-d) δ
7.50 (d, J = 7.3 Hz, 2H), 7.36 (t, J = 7.6 Hz, 2H), 7.25−7.21 (m,1H), 6.88−6.80 (m,
1H), 6.75 (dd, J = 13.9, 1.6 Hz, 1H), 6.55 (dd, J = 14.0, 8.0 Hz, 1H), 3.49−3.18 (m,
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2H), 3.08−2.82 (m, 2H), 1.85 (dd, J = 40.0, 10.0 Hz, 4H), 1.45−1.25 (m, 4H); 13C{1H}
NMR (100 MHz, Chloroform-d) δ 141.8, 133.9, 133.5, 131.8, 128.5, 126.4, 126.0,
117.7, 114.5, 113.0, 55.4, 55.3, 31.5, 31.5, 24.2.
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1,2,3,4-Tetrahydrophenazine (3p).18 Cyclohexanone (21 μL, 0.2 mmol) and
1,2-diaminobenzene (37.8 mg, 0.35 mmol) was used as the substrate under the given
reaction conditions. The residue was purified by column chromatography (silica gel,
petroleum ether/ethyl acetate = 20:1) to give 3o as white solid, 13.7 mg, yield 37%.
Mp: 101−103 oC. 1H NMR (400 MHz, Chloroform-d) δ 7.98 (dd, J = 6.3, 3.5 Hz, 2H),
7.67 (dd, J = 6.4, 3.4 Hz, 2H), 3.17 (s, 4H), 2.06−2.03 (m, 4H); 13C{1H} NMR (100
MHz, Chloroform-d) δ 154.1, 141.1, 128.9, 128.3, 33.1, 22.7.
N,N’-Diphenethylbenzene-1,2-diamine (3q).14c Cyclohexanone (21 μL, 0.2 mmol)
and 2-phenylethanamine (88 μL, 0.7 mmol) was used as the substrate under the given
reaction conditions. The residue was purified by column chromatography on silica gel
(petroleum ether/ethyl acetate = 95:5) to yield the desired product 3p as yellow solid
(11.5 mg, 18% yield), mp 85-86 oC. 1H NMR (400 MHz, CDCl3, ppm) δ 7.33-7.29 (m,
4H), 7.23-7.21 (m, 6H), 6.79-6.78 (m, 4H), 6.70-6.68 (m, 2H), 3.32 (t, J = 6.8 Hz,
4H), 2.92 (t, J = 6.8 Hz, 4H); 13C{1H} NMR (100 MHz, CDCl3, ppm) δ 139.4, 137.1,
128.7, 128.5, 126.4, 119.3, 112.0, 45.5, 35.8.
N1,N2-Diphenylbenzene-1,2-diamine (3s).14a Cyclohexanone (21 μL, 0.2 mmol),
aniline (64 μL, 0.7 mmol) was used as the substrate under the given reaction
conditions. The residue was purified by column chromatography on silica gel
(petroleum ether/ethyl acetate = 50:1) to give the desired product 3r as yellow solid
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(14.8 mg, yield 28%). mp 105-107 oC. 1H NMR (400 MHz, CDCl3, ppm) δ 7.30 - 7.28
(m, 2H), 7.26 - 7.22 (m, 4H), 6.95 - 6.88 (m, 8H), 5.66 (br, 2H); 13C NMR (100 MHz,
CDCl3, ppm) δ 143.9, 134.8, 129.3, 122.9, 120.5, 120.2, 117.2.
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N-(Pentan-3-yl)naphthalen-2-amine (5a). β-Tetralone (54 μL, 0.4 mmol) and
cyclohexanamine (23 μL, 0.2 mmol) were used as the substrates under the given
reaction conditions. The residue was purified by column chromatography (silica gel,
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petroleum ether/ethyl acetate = 100:1) to give 5a as red oil, 32.4 mg, yield 76%. H
NMR (400 MHz, Chloroform-d) δ 7.67−7.54 (m, 3H), 7.33 (t, J = 7.5 Hz, 1H), 7.15 (t,
J = 7.4 Hz, 1H), 6.85 (dd, J = 8.7, 2.2 Hz, 1H), 6.79−6.72 (m, 1H), 3.37 (p, J = 6.0 Hz,
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1H), 1.71−1.60 (m, 2H), 1.59−1.48 (m, 2H), 0.96 (t, J = 7.4 Hz, 6H); C{1H} NMR
(100 MHz, Chloroform-d) δ 145.8, 135.3, 128.9, 127.6, 127.1, 126.2, 125.7, 121.5,
118.2, 104.4, 55.4, 26.7, 10.2; HRMS calcd. for: C15H20N+ (M+H)+ 214.1590, found
214.1590.
N-(1-Phenylethyl)naphthalen-2-amine (5b).19 β-Tetralone (54 μL, 0.4 mmol) and
DL-alpha-methylbenzylamin (26 μL, 0.2 mmol) were used as the substrates under the
given reaction conditions. The residue was purified by column chromatography (silica
gel, petroleum ether/ethyl acetate = 100:1) to give 5b as red oil, 32.1 mg, yield 65%.
1H NMR (400 MHz, Chloroform-d) δ 7.63−7.57 (m, 2H), 7.47 (d, J = 8.3 Hz, 1H),
7.41 (d, J = 7.4 Hz, 2H), 7.33−7.20 (m, 4H), 7.15 (t, J = 7.5 Hz, 1H), 6.89 (dd, J = 8.8,
2.2 Hz, 1H), 6.65 (s, 1H), 4.62 (q, J = 6.7 Hz, 1H), 1.58 (d, J = 6.7 Hz, 3H); 13C{1H}
NMR (100 MHz, Chloroform-d) δ 144.6, 144.4, 134.9, 128.8, 128.7, 127.5, 127.5,
127.0, 126.1, 126.0, 125.9, 122.0, 118.0, 106.1, 53.8, 24.7.
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N-Cyclopentylnaphthalen-2-amine (5c). β-Tetralone (54 μL, 0.4 mmol) and
cyclopentylamine (20 μL, 0.2 mmol) were used as the substrates under the given
reaction conditions. The residue was purified by column chromatography (silica gel,
petroleum ether/ethyl acetate = 100:1) to give 5c as brown oil, 32.9 mg, yield 78%. 1H
NMR (400 MHz, Chloroform-d) δ 7.67−7.57 (m, 3H), 7.34 (t, J = 7.5 Hz, 1H), 7.17 (t,
J = 7.4 Hz, 1H), 6.90−6.73 (m, 2H), 3.90 (p, J = 6.2 Hz, 1H), 2.12−2.04 (m, 2H),
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1.79−1.62 (m, 4H), 1.56−1.48 (m, 2H); C{1H} NMR (100 MHz, Chloroform-d) δ
145.6, 135.2, 128.8, 127.6, 127.2, 126.2, 125.82 121.7, 118.3, 104.8, 54.6, 33.5, 24.1;
HRMS calcd. for: C15H18N+ (M+H)+ 212.1434, found 212.1432.
N-Cyclohexylnaphthalen-2-amine (5d, CAS: 23761-52-6).20 β-Tetralone (54 μL, 0.4
mmol) and cyclohexylamine (23 μL, 0.2 mmol) were used as the substrates under the
given reaction conditions. The residue was purified by column chromatography (silica
gel, petroleum ether/ethyl acetate = 100:1) to give 5d as yellow oil, 31.9 mg, yield
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71%. H NMR (400 MHz, Chloroform-d) δ 7.65−7.57 (m, 3H), 7.33 (t, J = 7.5 Hz,
1H), 7.16 (t, J = 7.4 Hz, 1H), 6.86−6.77 (m, 2H), 3.43−3.35 (m, 1H), 2.17−2.09 (m,
2H), 1.79 (dt, J = 13.0, 3.5 Hz, 2H), 1.68 (dt, J = 12.5, 3.5 Hz, 1H), 1.47−1.38 (m,
2H), 1.28−1.17 (m, 3H); 13C{1H} NMR (100 MHz, Chloroform-d) δ 144.9, 135.3,
128.9, 127.6, 127.2, 126.2, 125.7, 121.7, 118.2, 104.7, 51.7, 33.3, 25.9, 25.0.
N-Phenylnaphthalen-2-amine (5e, CAS: 135-88-6).13 β-Tetralone (54 μL, 0.4 mmol)
and aniline (18 μL, 0.2 mmol) were used as the substrates under the given reaction
conditions. The residue was purified by column chromatography (silica gel, petroleum
ether/ethyl acetate = 100:1) to give 5e as yellow solid, 27.6 mg, yield 63%. Mp:
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104−106 oC. 1H NMR (400 MHz, Chloroform-d) δ 7.74 (d, J = 8.9 Hz, 2H), 7.65 (d, J
= 8.2 Hz, 1H), 7.48 (s, 1H), 7.41 (t, J = 7.5 Hz, 1H), 7.34−7.29 (m, 3H), 7.25−7.23 (m,
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1H), 7.19 (d, J = 7.8 Hz, 2H), 7.00 (t, J = 7.3 Hz, 1H); C{1H} NMR (100 MHz,
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Chloroform-d) δ 142.7, 140.7, 134.6, 129.4, 129.2, 127.6, 126.5, 126.5, 123.6, 121.7,
120.0, 118.4, 112.0.
2-(Naphthalen-2-ylamino)benzonitrile (5f). β-Tetralone (54 μL, 0.4 mmol) and
2-aminobenzonitrile (23.6 mg, 0.2 mmol) were used as the substrates under the given
reaction conditions. The residue was purified by column chromatography (silica gel,
petroleum ether/ethyl acetate = 20:1) to give 5f as white solid, 16.1 mg, yield 33%.
Mp:119−121 oC. 1H NMR (400 MHz, Chloroform-d) δ 7.82 (t, J = 9.2 Hz, 2H), 7.73
(d, J = 8.1 Hz, 1H), 7.58 (s, 1H), 7.55−7.51 (m, 1H), 7.49−7.36 (m, 3H), 7.34−7.27
(m, 2H), 6.87 (t, J = 7.5 Hz, 1H), 6.52 (s, 1H); 13C{1H} NMR (100 MHz,
Chloroform-d) δ 147.1, 137.4, 134.1, 133.9, 133.1, 130.6, 129.5, 127.7, 127.0, 126.7,
+
125.0, 121.8, 119.5, 117.6, 117.5, 114.5, 98.7; HRMS calcd. for: C17H13N2 (M+H)+
245.1073, found 245.1074.
N-(m-Tolyl)naphthalen-2-amine (5g, CAS: 76783-57-8).21 β-Tetralone (54 μL, 0.4
mmol) and m-toluidine (21 μL, 0.2 mmol) were used as the substrates under the
given reaction conditions. The residue was purified by column chromatography (silica
gel, petroleum ether/ethyl acetate = 100:1) to give 5g as red oil, 29.4 mg, yield 63%.
1H NMR (400 MHz, Chloroform-d) δ 7.73 (d, J = 8.5 Hz, 2H), 7.64 (d, J = 8.2 Hz,
1H), 7.43−7.37 (m, 2H), 7.29 (t, J = 7.5 Hz, 1H), 7.23−7.16 (m, 2H), 6.98 (d, J = 8.0
Hz, 2H), 6.80 (d, J = 7.4 Hz, 1H), 2.33 (s, 3H); 13C{1H} NMR (100 MHz,
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Chloroform-d) δ 142.8, 140.9, 139.3, 134.6, 129.2, 129.1, 129.1, 127.6, 126.5, 126.4,
123.5, 122.4, 120.1, 119.0, 115.4, 111.7, 21.5.
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N-(4-Methoxyphenyl)naphthalen-2-amine (5h, CAS: 6949-67-3).22 β-Tetralone (54
μL, 0.4 mmol) and p-anisidine (24.6 mg, 0.2 mmol) were used as the substrates under
the given reaction conditions. The residue was purified by column chromatography
(silica gel, petroleum ether/ethyl acetate = 20:1) to give 5h as yellow solid, 22.9 mg,
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yield 46%. Mp: 104−106 C. H NMR (400 MHz, Chloroform-d) δ 7.72−7.68 (m,
2H), 7.58 (d, J = 8.2 Hz, 1H), 7.36 (t, J = 7.5 Hz, 1H), 7.26 (s, 1H), 7.22 (s, 1H), 7.16
(d, J = 8.8 Hz, 2H), 7.11 (dd, J = 8.8, 2.2 Hz, 1H), 6.94−6.88 (m, 2H), 3.82 (s, 3H);
13C{1H} NMR (100 MHz, Chloroform-d) δ 155.6, 142.9, 135.5, 134.8, 129.1, 128.6,
127.6, 126.4, 126.2, 122.9, 122.6, 118.9, 114.7, 108.8, 55.5.
N-(4-Fluorophenyl)naphthalen-2-amine (5i, CAS: 582-05-8).22 β-Tetralone (54 μL,
0.4 mmol) and 4-fluoroaniline (19 μL, 0.2 mmol) were used as the substrates under
the given reaction conditions. The residue was purified by column chromatography
(silica gel, petroleum ether/ethyl acetate = 20:1) to give 5i as yellow solid, 18.1 mg,
o
1
yield 38%. Mp: 84−86 C. H NMR (400 MHz, Chloroform-d) δ 7.72−7.76 (m, 2H),
7.60 (d, J = 8.2 Hz, 1H), 7.41−7.36 (m, 1H), 7.30−7.25 (m, 2H), 7.13−7.08 (m, 3H),
13
7.00 (t, J = 8.6 Hz, 2H); C{1H} NMR (100 MHz, Chloroform-d) δ 158.2 (d, JC-F
=
240.6 Hz), 141.6, 138.7 (d, J = 2.5 Hz), 134.6, 129.3, 128.9, 127.6, 126.5, 126.3,
123.3, 121.0 (d, J = 7.8 Hz), 119.3, 116.0 (d, J = 22.4 Hz), 110.3.
N-(4-chlorophenyl)naphthalen-2-amine (5j, CAS: 55566-60-4).23 β-Tetralone (54 μL,
0.4 mmol) and 4-chloroaniline (25.5 mg, 0.2 mmol) were used as the substrates under
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the given reaction conditions. The residue was purified by column chromatography
(silica gel, petroleum ether/ethyl acetate = 20:1) to give 5j as red solid, 23.3 mg, yield
46%. Mp: 102−104 oC. 1H NMR (400 MHz, Chloroform-d) δ 7.74 (d, J = 8.5 Hz, 2H),
7.64 (d, J = 8.2 Hz, 1H), 7.44−7.38 (m, 2H), 7.31 (t, J = 7.5 Hz, 1H), 7.26−7.22 (m,
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2H), 7.18 (dd, J = 8.8, 2.3 Hz, 1H), 7.09−7.04 (m, 2H); C{1H} NMR (100 MHz,
Chloroform-d) δ 141.6, 140.3, 134.5, 129.3, 129.3, 127.7, 126.6, 126.5, 125.9, 123.8,
120.0, 119.3, 112.1.
N-(4-Bromophenyl)naphthalen-2-amine (5k, 70539-21-8).23 β-Tetralone (54 μL, 0.4
mmol) and 4-bromoaniline (34.4 mg, 0.2 mmol) were used as the substrates under the
given reaction conditions. The residue was purified by column chromatography (silica
gel, petroleum ether/ethyl acetate = 20:1) to give 5k as white solid, 32.7 mg, yield
55%. Mp: 113−115 oC. 1H NMR (400 MHz, Chloroform-d) δ 7.74 (d, J = 8.6 Hz, 2H),
7.64 (d, J = 8.2 Hz, 1H), 7.44−7.35 (m, 4H), 7.32 (t, J = 7.5 Hz, 1H), 7.18 (dd, J = 8.8,
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2.3 Hz, 1H), 7.04−6.98 (m, 2H); C{1H} NMR (100 MHz, Chloroform-d) δ 142.2,
140.1, 134.5, 132.3, 129.4, 129.3, 127.7, 126.6, 126.5, 123.8, 120.1, 119.5, 113.0,
112.4.
N-(4-(Trifluoromethoxy)phenyl)naphthalen-2-amine (5l). β-Tetralone (54 μL, 0.4
mmol) and 4-trifluoromethoxyaniline (27 μL, 0.2 mmol) were used as the substrates
under the given reaction conditions. The residue was purified by column
chromatography (silica gel, petroleum ether/ethyl acetate = 20:1) to give 5l as yellow
solid, 25.5 mg, yield 42%. Mp: 59−61 oC. 1H NMR (400 MHz, Chloroform-d) δ 7.75
(d, J = 8.7 Hz, 2H), 7.65 (d, J = 8.2 Hz, 1H), 7.44−7.39 (m, 2H), 7.32 (t, J = 7.4 Hz,
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1H), 7.19 (dd, J = 8.8, 2.2 Hz, 1H), 7.15−7.08 (m, 4H); C{1H} NMR (100 MHz,
Chloroform-d) δ 143.0, 141.9, 140.2, 134.5, 129.4, 129.3, 127.7, 126.6, 126.5, 123.8,
122.4, 120.6 (q, JC-F = 256.3 Hz), 120.1, 118.6, 112.4; HRMS calcd. for:
C17H13F3NO+ (M+H)+ 304.0944, found 304.0947.
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Methyl 4-(Naphthalen-2-ylamino)benzoate (5m).24 β-Tetralone (54 μL, 0.4 mmol)
and methyl 4-aminobenzoate (30.2 mg, 0.2 mmol) were used as the substrates under
the given reaction conditions. The residue was purified by column chromatography
(silica gel, petroleum ether/ethyl acetate = 20:1) to give 5m as yellow solid, 30.5 mg,
o
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yield 55%. Mp: 177−179 C. H NMR (400 MHz, Chloroform-d) δ 7.98−7.93 (m,
2H), 7.79 (t, J = 7.9 Hz, 2H), 7.71 (d, J = 8.2 Hz, 1H), 7.57 (d, J = 2.3 Hz, 1H),
7.48−7.42 (m, 1H), 7.40−7.35 (m, 1H), 7.29 (dd, J = 8.8, 2.3 Hz, 1H), 7.09−7.04 (m,
2H), 3.88 (s, 3H); 13C{1H} NMR (100 MHz, Chloroform-d) δ 167.0, 147.9, 138.4,
134.3, 131.5, 130.1, 129.4, 127.7, 126.8, 126.6, 124.5, 121.4, 121.2, 115.5, 114.9,
51.7.
N-(4-(Trifluoromethyl)phenyl)naphthalen-2-amine (5n). β-Tetralone (54 μL, 0.4
mmol) and 4-aminobenzotrifluoride (25 μL, 0.2 mmol) were used as the substrates
under the given reaction conditions. The residue was purified by column
chromatography (silica gel, petroleum ether/ethyl acetate = 20:1) to give 5n as yellow
o
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solid, 39.6 mg, yield 69%. Mp: 96−98 C. H NMR (400 MHz, Chloroform-d) δ
7.80−7.76 (m, 2H), 7.69 (d, J = 8.2 Hz, 1H), 7.54−7.47 (m, 3H), 7.44 (t, J = 7.1 Hz,
1H), 7.37 (t, J = 7.5 Hz, 1H), 7.25 (dd, J = 8.8, 2.1 Hz, 1H), 7.10 (d, J = 8.5 Hz, 2H);
13C{1H} NMR (100 MHz, Chloroform-d) δ 146.6, 138.8, 134.3, 130.0, 129.4, 127.7,
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126.8, 126.7 (q, J = 4.0 Hz), 126.7, 124.6 (q, JC-F = 270.5 Hz), 124.4, 122.0 (q, J =
32.4 Hz), 120.9, 115.7, 114.9; HRMS calcd. for: C17H13F3N+ (M+H)+ 288.0994,
found 288.0998.
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4-(Naphthalen-2-ylamino)benzonitrile (5o, CAS: 1292486-76-0).25 β-Tetralone (54
μL, 0.4 mmol) and 4-aminobenzonitrile (23.6 mg, 0.2 mmol) were used as the
substrates under the given reaction conditions. The residue was purified by column
chromatography (silica gel, petroleum ether/ethyl acetate = 20:1) to give 5o as yellow
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solid, 31.8 mg, yield 65%. Mp: 142−144 oC. H NMR (400 MHz, Chloroform-d) δ
7.81 (t, J = 8.4 Hz, 2H), 7.72 (d, J = 8.1 Hz, 1H), 7.57 (s, 1H), 7.51−7.37 (m, 4H),
13
7.28 (dd, J = 8.8, 2.1 Hz, 1H), 7.04 (d, J = 8.8 Hz, 2H), 6.30 (s, 1H); C{1H} NMR
(100 MHz, Chloroform-d) δ 147.8, 137.6, 134.1, 133.8, 130.4, 129.5, 127.7, 126.9,
126.7, 124.9, 121.5, 119.9, 116.7, 115.2, 101.7.
ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the ACS Publications
website at DOI: 10.1021/acs.joc
Copies of 1H NMR and 13C NMR spectra for all products
AUTHOR INFORMATION
Corresponding Author
*E-mail: hwhuang@xtu.edu.cn.
*E-mail: gjdeng@xtu.edu.cn.
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Notes
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The authors declare no competing financial interest.
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ACKNOWLEDGMENT
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We are grateful for financial support from the National Natural Science Foundation of
China (21871226, 21372187), the Science and Technology Planning Project of Hunan
Province (2019RS2039), and the Collaborative Innovation Center of New Chemical
Technologies for Environmental Benignity and Efficient Resource Utilization.
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