Iodine-catalyzed coupling of β-hydroxyketones with aromatic amines to form β-aminoketones and Benzo[h]quinolones

Article abstract of DOI:10.1016/j.tet.2019.02.041

An iodine-catalyzed coupling of β-hydroxyketones with aromatic amines to yield β-aminoketones and benzo[h]quinolones had been developed. Noble metallic catalysts, oxidants, α β-unsaturated ketone intermediates and aza-Michael addition were not involved in this coupling reaction which made it unique when compared to other reactions reported in literature. Inexpensive iodine catalyst, easy accessible raw materials, mild reaction conditions, good functional group tolerance and excellent selectivity made this coupling reaction be a practical method. This reaction can also be scaled up.

Full text of DOI:10.1016/j.tet.2019.02.041

Accepted Manuscript
Iodine-catalyzed coupling of β-hydroxyketones with aromatic amines to form β-
aminoketones and Benzo[h]quinolones
Changqing Miao, Liya Jiang, Lanhui Ren, Qingxia Xue, Fang Yan, Weiwei Shi, Xinjian
Li, Jiwen Sheng, Shuangshuang Kai
PII:
S0040-4020(19)30200-5
https://doi.org/10.1016/j.tet.2019.02.041
TET 30164
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 21 November 2018
Revised Date: 18 February 2019
Accepted Date: 19 February 2019
Please cite this article as: Miao C, Jiang L, Ren L, Xue Q, Yan F, Shi W, Li X, Sheng J, Kai S,
Iodine-catalyzed coupling of β-hydroxyketones with aromatic amines to form β-aminoketones and
Benzo[h]quinolones, Tetrahedron (2019), doi: https://doi.org/10.1016/j.tet.2019.02.041.
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ACCEPTED MANUSCRIPT
Iodine-Catalyzed Coupling of β-Hydroxyketones with Aromatic
Amines to Form β-Aminoketones and Benzo[h]quinolones
Changqing Miao,†, ‡ Liya Jiang,†, ‡ Lanhui Ren,*, † Qingxia Xue,† Fang Yan,† Weiwei Shi,† Xinjian
Li,† Jiwen Sheng† and Shuangshuang Kai†
†College of Pharmacy, Weifang Medical University, Weifang 261053, P. R. China; E-mail:
Ren_lanhui@163.com
‡Changqing Miao and Liya Jiang contributed equally to this work
Abstract: A iodine-catalyzed coupling of β-hydroxyketones with aromatic amines to yield
β-aminoketones and benzo[h]quinolones had been developed. Noble metallic catalysts, oxidants, α,
β-unsaturated ketone intermediates and aza-Michael addition were not involved in this coupling
reaction which made it unique when compared to other reactions reported in literatures.
Inexpensive iodine catalyst, easy accessible raw materials, mild reaction conditions, good
functional group tolerance and excellent selectivity made this coupling reaction be a practical
method. This reaction can also be scaled up.
Keywords: Iodine, Coupling, β-Hydroxyketones, β-Aminoketones, Benzo[h]quinolones
INTRODUCTION
β-Aminoketones are important structures found in many bioactive molecules and pharmaceutical
agents, and are very useful intermediates in the synthesis of β-aminoacids, β-aminoalcohols,
1,3-alkamines, lactams, nikkomycins and neopolyoxines which also find wide applications in fine
chemicals and pharmaceuticals.1 Traditionally, a classical method for the construction of
β-aminoketones is Mannich reaction (Scheme 1, eq 1),2 however, the drawbacks such as long
reaction times, low yields and harsh conditions limit its application in the synthesis of complex
molecules. Aza-Michael addition is another method for the synthesis of β-aminoketones using
conjugate addition of amines to α, β-unsaturated ketones with such advantages as simplicity and
atom economy (Scheme 1, eq 2).3-7 A variety of reagents involved stoichiometric or catalytic
amounts of Lewis acids,5 transition-metals,6 and organic compounds7 had been reported as
catalysts for aza-Michael addition. But the polymerization of labile α, β-unsaturated carbonyl
compounds caused by acidic or basic catalysts limited the application of aza-Michael addition in
many fields. To address this challenge, the Pd-catalyzed oxidative amination of homoallylic
alcohols8 or allyl alcohols9 to afford β-aminoketones using TBHP or O2 as oxidants respectively
was reported lately (Scheme 1, eq 3 and 4). To our knowledge, non-metal catalyzed coupling of
β-hydroxyketones with amines to form β-aminoketones in one step without oxidants had not been
studied.
Herein, we disclosed a iodine-catalyzed coupling of β-hydroxyketones with aromatic amines
to yield β-aminoketones and benzo[h]quinolones. There are many differences between this
1

ACCEPTED MANUSCRIPT
coupling reaction and other reactions reported in literatures (Scheme 1, eq 5), for exemple,
non-metal catalyst, no oxidant, no α, β-unsaturated ketone intermediates and aza-Michael addition.
This approach has advantages of easy accessible raw materials, mild reaction conditions, good
functional group tolerance and excellent selectivity, and can also be scaled up.
Previous work:
R1
O
O
O
H
(1)
(2)
NH
R3
R1
O
R2
H
H
R4
N
R4
R2 R3
R1
O
R5
cat.
NH
R1
R2
R5
R6
N
R6
R2
cat.: Lewis acids, transitionꢀmetal catalysts, organocatalysts
H
N
NH2
CH3
Pd(TFA)2, TBHP
MeCN, 70 oC
(3)
(4)
R7
R8
R7
HO
O
H
N
NH2
R9
Pd(OAc)2 or Pd(TFA)2, O2
NaOAc, AcOH,Toluene, 80 oC
HO
R8
O
R9
This work:
H
N
O
NH2
R'
I2 (10 mol%)
(5)
R
R
HO
R'
DMSO, rt, 8 h
O
Non-metallic catalyst
No oxidant
No experienced unsaturated
ketone and Michael addition
Scheme 1. Strategies for the Construction of β-AminoKetones
RESULTS AND DISCUSSION
We initiated this study with commercially available aniline (1a) and 4-hydroxybutan-2-one
(1b) as template substrates for the optimization of reaction parameters including catalyst, solvent
and reaction time to identify the optimal reactions conditions (Table 1). To our delight, when I2
(10 mol%) was employed as catalyst in THF, the 4-(phenylamino)butan-2-one (1c) was obtained
in 64% isolated yield (Table 1, entry 1). After detailed examinations of different solvents such as
MeCN, ethyl acetate, toluene, EtOH, DMF, DMSO, MeOH, H2O, 1,2-dichloroethane, 1,4-dioxane
and solvent-free system (Table 1, entries 2-12), the DMSO was selected for the next optimization
study owing to the 93% isolated yield of 4-(phenylamino)butan-2-one (1c) (Table 1, entry 8). Next,
screening of other iodine compounds such as H4NI, KI, NaI, ZnI2 and (CH3)4NI revealed that I2
catalyze the process more efficient than other iodine compounds (Table 1, entries 13-17). As
expected, no 4-(phenylamino)butan-2-one (1c) could be detected in absence of iodine catalyst
(Table 1, entry 18). Then we studied the amount of I2 and found that 10 mol% was the best choice
(Table 1, entries 19-22). After the reaction time were studied (Table 1, entries 23-26), we obtained
the optimal reactions conditions, viz., 10 mol% I2 as catalyst, 2 mL DMSO as solvent at room
temperature for 8 h (Table 1, entry 26). Control reactions were carried out in nitrogen atmosphere
also yielded 4-(phenylamino)butan-2-one (1c) in 66% and 93% isolated yields respectively (Table
2

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1, entries 1 and 26) which illustrated O2 was not involved in the reaction.
Table 1. Optimization of Reaction Conditions
entry
1
cat. (mol%)
I2 (10)
I2 (10)
I2 (10)
I2 (10)
I2 (10)
I2 (10)
I2 (10)
I2 (10)
I2 (10)
I2 (10)
I2 (10)
I2 (10)
H4NI (10)
KI (10)
NaI (10)
ZnI2 (10)
(CH3)4NI (10)
-
solvent
THF
yielda (%)
64 (66b)
74
2
MeCN
3
Ethyl acetate
Toluene
EtOH
34
4
76
5
58
6
-
63
7
DMF
90
8
DMSO
MeOH
93
9
46
10
11
12
13
14
15
16
17
18
19
20
21
22
23c
24d
25e
26f
H2O
22
1,2-Dichloroethane
1,4-Dioxane
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
68
62
30
trace
48
41
28
n.r.
78
I2 (3)
I2 (5)
81
I2 (6)
82
I2 (8)
82
I2 (10)
I2 (10)
I2 (10)
58
68
83
94 (93b)
I2 (10)
a
b
c
d
Isolated yield, n.r. = no reaction. Reaction was studied in nitrogen atmosphere. Reaction time was 2 h.
Reaction time was 4 h. e Reaction time was 6 h. f Reaction time was 8 h.
On the basis of the optimized conditions, the generality of the catalyst system was assessed
on an array of substituted aromatic amine which have electron-donating and electron-withdrawing
groups in the arene. In all cases, the corresponding β-aminoketones (monoalkylated products)
were obtained in moderate to good yields (Table 2). These results show that the reaction have
good functional group tolerance and excellent selectivity which made this reaction be a practical
synthetic method. Para, meta and ortho substitution have different impacts on the reaction with
the results as yields of para substituted aromatic amines were highest, followed by meta
substituted aromatic amines, ortho substituted aromatic amines final (Table 2, 2c-12c, 14c-26c). It
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might be due to the steric hindrance of ortho-substituent group. The electron-rich aromatic amines
provided higher yields than electron-deficient aromatic amines under the standard conditions.
Table 2. Scope of Substrates of Iodine-catalyzed Coupling of β-Hydroxyketones with
Aromatic Amines
entry
1
product
structure
yielda (%)
94
1c
2
3
4
2c
3c
4c
73
86
90
5
6
7
5c
6c
7c
71
75
77
8
9
8c
9c
40
50
4

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10
10c
44
a Isolated yield. b Reaction time was 24 h.
Table 2. (Contd.)
entry
product
structure
yielda (%)
72
11
11c
12
13
12c
13c
79
92
O
14
15
16
14c
15c
16c
71
74
50
H3C
N
H
OCH3
17
18
19
17c
18c
19c
41
42 (70b)
45 (71b)
O
38 (41b)
20
20c
H3C
N
H
NO2
5

ACCEPTED MANUSCRIPT
49 (50b)
21
21c
a Isolated yield. b Reaction time was 24 h.
Table 2. (Contd.)
entry
product
structure
yielda (%)
56 (56b)
22
22c
23
24
23c
24c
78 (79b)
77 (79b)
25
26
25c
26c
64 (63b)
87 (89b)
O
O
OCH3
H3C
N
H
27
28
29
27c
28c
29c
59 (58b)
76
84
6

ACCEPTED MANUSCRIPT
30
90
30c
a Isolated yield. b Reaction time was 24 h.
Table 2. (Contd.)
entry
product
structure
yielda (%)
80
31
31c
32
33
34
32c
33c
34c
93
85
86
35
35c
51
36
37
36c
37c
37
51
7

ACCEPTED MANUSCRIPT
38
39
38c
50
39c
71b
a Isolated yield. b Reaction time was 24 h.
Table 2. (Contd.)
entry
product
structure
yielda (%)
77b
40
40c
41
41c
81b
a Isolated yield. b Reaction time was 24 h.
The substrates with strong electron-withdrawing group in the aromatic rings which can be
utilized for further synthetic transformations, such as -CF3 (Table 2, 18c and 19c), -NO2 (Table 2,
20c-22c), -CN (Table 2, 23c and 24c), -COOCH3 (Table 2, 25c and 26c), -SO2CH3 (Table 2, 27c),
were tolerated in the reaction in moderate to good yields. We ran experiments with the
electron-deficient aromatic amines as substrates for 24 h. The substrates with -CF3 group in the
aromatic rings (Table 2, 18c and 19c) gave higher yields comparing with the standard conditions.
The substrates with -NO2 (Table 2, 20c-22c), -CN (Table 2, 23c and 24c), -COOCH3 (Table 2, 25c
and 26c), -SO2CH3 (Table 2, 27c) in the aromatic rings gave similar yields comparing with the
standard conditions. The β-aminoketones with halo group in the ortho-position of NH (Table 2, 2c,
5c, 8c) which can be used for the synthesis of 3-substituted indolines were obtained in good yields.
Quinolin-8-amine and 4-hydroxybutan-2-one underwent this protocol to afford product in 51%
yields (Table 2, 35c). The reaction was also compatible with 2° amine to afford the desired
product in moderate yield (Table 2, 36c). Notably, when 1-aminonaphthalenes were utilized as the
substrates, the corresponding products benzo[h]quinolones were obtained in good yields (Table 2,
37c, 38c). Good yields were obtained when 3-hydroxy-1-phenylpropan-1-one was used as
substrates (Table 2, 39c-41c).
8

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Scheme 2. Gram Scale Reactions (isolated yield)
The practical applicability of this protocol was demonstrated. We used 4-hydroxybutan-2-one
and aromatic amines as the test substrates, working on gram scale at room temperature until
complete consumption of starting material as monitored by TLC or 72 h. The desired products
were obtained in good isolated yield (Scheme 2). These results suggested that this protocol is a
practical process for the preparation of β-aminoketones and benzo[h]quinolones.
9

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O
O
1H NMR and GC-MS
no reaction
I2 (10 mol%)
(1)
(2)
DMSO-d6 (2 mL), rt, 1 h
H3C
H3C
OH
, 1 mmol
H3C
1a
O
CH3
N
NH2
O
CH3
standard condition
OH
CH3
H3C
H3C
H
1d
1b
no reaction
O
, 1 mmol
, 1 mmol
NH2
O
standard condition
(3)
H3COOC
no reaction
N
H
H3COOC
OH
2d
1b
, 1 mmol
, 1 mmol
NH2
H
standard condition
N
NC
OH
(4)
(5)
(6)
NC
3d
1b
no reaction
, 1 mmol
, 1 mmol
NH2
H
OH
N
standard condition
4d, 1 mmol
1b, 1 mmol
no reaction
N O
O
H
NH2
DMSO (2 mL), rt, 8 h
5d
1b
no reaction
, 1 mmol
, 1 mmol
O
NH2
No cyclohex-2-en-1-one, aniline and
3-(phenylamino)cyclohexan-1-one
are detected
standard condition
(7)
(8)
5d
1b
, 1 mmol
, 1 mmol
OH
NH2
standard condition
N
H
6d, 1 mmol
1b, 1 mmol
no reaction
Scheme 3. Control Experiments
To gain more insight into the mechanism for the coupling of β-hydroxyketones with aromatic
amines to form β-aminoketones, several control experiments had been conducted (Scheme 3).
According to the literature,10 we hypothesized this coupling reaction experienced proton
abstraction, synchronic with the C-O bond rupture of β-hydroxyketones by the catalyst iodine to
yield α, β-unsaturated ketones (electron-deficient olefins) and followed by aza-Michael addition
with amines to afford β-aminoketones. But, when the reaction proceeded with
4-hydroxybutan-2-one (1a), I2, DMSO-d6, no reaction occurred (Scheme 3, eq 1) detected by
1HNMR (Fig. 1, see the ESI) and GC-MS. Other β-hydroxy compounds which also could yield
electron-deficient
olefins
were
utilized
as
the
substrates,
for
example
4-hydroxy-4-methylpentan-2-one
(1d), methyl
4-hydroxy-2-oxobutanoate
(2d),
3-hydroxypropanenitrile (3d), 2-phenylethan-1-ol (4d), no coupling reactions occured (Scheme 3,
eq 2-5). The reaction also did not occur when the cyclohex-2-en-1-one and aniline were used as
10

ACCEPTED MANUSCRIPT
the substrates without I2 (Scheme 3, eq 6). When the reaction was conducted with
cyclohex-2-en-1-one and aniline as the substrates at standard condition, no cyclohex-2-en-1-one,
aniline and 3-(phenylamino)cyclohexan-1-one were detected (Scheme 3, eq 7). With the above
results, we thought this coupling reaction did not experienced α, β-unsaturated ketones and
aza-Michael addition. According to the literature,11 I2 may facilitate the generation of carbocation
from the activated alcohols. We hypothesized the carbocation is involved in this coupling reaction.
But 4-hydroxy-4-methylpentan-2-one (1d) and benzyl alcohol (6d) which could yield more stable
carbocations (3° and benzyl carbocation) were used as the substrates at standard condition, no
coupling reactions occured (Scheme 3, eq 2 and 8). It is supposed that the carbocation is not
involved in this coupling reaction.
Figure 1. 1H NMR spectras of the coupling reaction of 4-hydroxybutan-2-one with aniline at
various reaction times
Figure 2. 13C NMR spectra of the coupling reaction of 4-hydroxybutan-2-one with aniline using I2
11

ACCEPTED MANUSCRIPT
as catalyst
The H NMR and 13C NMR were used to measure structural changes during the coupling
reaction at standard condition (Figure 1 and 2). The 1HNMR spectras indicated that the
4-hydroxybutan-2-one (1a) decrease and 4-(phenylamino)butan-2-one (1c) increase with the
extended reaction time. No -NH2 and -OH were detected in the whole coupling process, which
1
1
were detected obviously in absence of I2 (Fig. 2, see the ESI). We did not obtain the HNMR
1
spectra with prominent feature of olefins and aldehydes. The H NMR spectrums (Figure 1B and
1C) are very different from the spectrums of aniline and the product (1c). A resonance
characteristic of imine was displayed, which suggested that 4-hydroxybutan-2-one (1a) was
oxidized to aldehyde, then aldehyde reacted with aniline to generate imine. The 13C NMR
spectrum also demonstrated the generation of imine in our reaction system (Figure 2). D3CSCD3
was detected which illustrated dimethyl sulfoxide actively participated the coupling reaction.12
Based on the above results and previous reports, a tentative mechanism for iodine-catalyzed
coupling of β-hydroxyketones with aromatic amines to yield β-aminoketones was proposed in
Scheme 4. Initially, 4-hydroxybutan-2-one (1a) was oxidized to aldehyde A under the standard
condition, synchronic with generation of HI.13 Next, aldehyde A reacted with aniline to form
imine B quickly which could explain why no -CHO was detected.8 HI has strong reducing action
and decomposed to H2 and I2. Imine B was reduced to product (1c) by hydrogen. Some party of HI
reacted with DMSO to give intermediate C.12 Then, nucleophilic attack of I- on the iodide atom of
intermediate C takes place to regenerate I2 releasing DMS and H2O. Further studies aimed at more
detailed mechanism are in progress.
Scheme 4. Possible Reaction Pathway
CONCLUSION
In summary, a novel and efficient iodine-catalyzed coupling of β-hydroxyketones with
aromatic amines to yield β-aminoketones and benzo[h]quinolones had been developed. Noble
metallic catalysts, oxidants, α, β-unsaturated ketone intermediates and aza-Michael addition were
not involved in this coupling reaction. Many advantages such as inexpensive I2 catalyst, easy
accessible raw materials, mild reaction conditions, good functional group tolerance and excellent
selectivity made this approach be a practical process for the preparation of β-aminoketones and
12

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benzo[h]quinolones.
EXPERIMENTAL SECTION
General Considerations
All
the
reagents
including
aromatic
amines,
4-hydroxybutan-2-one,
3-hydroxy-1-phenylpropan-1-one, iodine, iodides, solvents were purchased from commercial
sources and were used without further purification. All chemical shift values refer to δ TMS = 0.00
ppm or CDCl3 (δ (1H), 7.26 ppm; δ (13C), 77.20 ppm). The HRMS analysis was obtained on a
Waters GC-TOF CA156 mass spectrometer. All the melting points were uncorrected. Analytical
TLC plates were viewed by UV light (254 nm).
General Experimental Procedure
A 25 mL RBF was subsequently charged with 1.0 mmol aromatic amines, 1.0 mmol
4-hydroxybutan-2-one, 10 mol% I2 (25.4 mg), 2 mL DMSO. The resulting mixture was performed
at room temperature for 8 h. After reaction was complete, the resulting mixture was poured into
water (20 mL) and extracted with ethyl acetate (3×10 mL). The combined organic extracts were
washed with brine (3×5 mL), then dried over Na2SO4 and concentrated in vacuum. The resulting
residue was purified by silica gel column chromatography (ethyl acetate / petroleum ether =
1:20-1:4) to afford the desired products.
Experimental Procedure on Gram Scale
A 100 mL RBF was subsequently charged with 10 mmol aromatic amines, 10 mmol
4-hydroxybutan-2-one, 10 mol% I2 (254 mg), 20 mL DMSO. The resulting mixture was
performed at room temperature until complete consumption of starting material as monitored by
TLC or 72 h. After reaction was complete, the resulting mixture was poured into water (200 mL).
If desired products were isolated as solids from aqueous solutions, desired products were treated
through vacuum filtering, washing with water and vacuum drying. If no solid precipitated, the
aqueous solutions were extracted with ethyl acetate (3×100 mL). The combined organic extracts
were washed with brine (3×50 mL), then dried over Na2SO4 and concentrated in vacuum. The
resulting residue was purified by silica gel column chromatography (ethyl acetate / petroleum
ether = 1:20-1:4) to afford the desired products.
The yields, properties and characterization of new compounds
4-(Phenylamino)butan-2-one 1c was isolated in 94% yield (153.2 mg). Yellow solid; mp:
81-82 °C; 1H NMR (400 MHz, CDCl3) δ 7.19 (t, J = 7.9 Hz, 2H), 6.72 (t, J = 7.3 Hz, 1H), 6.61 (d,
J = 7.7 Hz, 2H), 3.99 (s, 1H), 3.42 (t, J = 6.1 Hz, 2H), 2.74 (t, J = 6.1 Hz, 2H), 2.16 (s, 3H); 13
C
NMR (101 MHz, CDCl3) δ 208.19, 147.81, 129.42, 117.72, 113.12, 42.70, 38.46, 30.39; Known
compound.8
4-((2-Chlorophenyl)amino)butan-2-one 2c was isolated in 73% yield (144.1 mg). Yellow oil;
1H NMR (400 MHz, CDCl3) δ 7.25 (d, J = 9.9 Hz, 1H), 7.14 (t, J = 7.3 Hz, 1H), 6.65 (dd, J = 17.0,
8.2 Hz, 2H), 4.55 (s, 1H), 3.48 (q, J = 6.3 Hz, 2H), 2.78 (t, J = 6.3 Hz, 2H), 2.19 (s, 3H); 13C
NMR (101 MHz, CDCl3) δ 207.59, 143.75, 129.49, 127.96, 119.71, 117.61, 111.23, 42.79, 38.24,
30.55. HRMS (ESI) for C10H12ClNO, calcd: 197.0607, found: 197.0606.
4-((3-Chlorophenyl)amino)butan-2-one 3c was isolated in 86% yield (169.8 mg). Yellow oil;
1H NMR (400 MHz, CDCl3) δ 7.04 (t, J = 8.0 Hz, 1H), 6.64 (d, J = 7.9 Hz, 1H), 6.55 (s, 1H), 6.44
13

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(d, J = 8.2 Hz, 1H), 4.14 (s, 1H), 3.35 (s, 2H), 2.70 (t, J = 5.7 Hz, 2H), 2.14 (s, 3H); 13C NMR
(101 MHz, CDCl3) δ 207.99, 149.02, 135.06, 130.33, 117.31, 112.43, 111.41, 42.37, 38.16, 30.32.
HRMS (ESI) for C10H12ClNO, calcd: 197.0607, found: 197.0604.
4-((4-Chlorophenyl)amino)butan-2-one 4c was isolated in 90% yield (177.2 mg). Yellow
solid; mp: 71-73 °C; 1H NMR (400 MHz, CDCl3) δ 7.09 (d, J = 8.8 Hz, 2H), 6.50 (d, J = 8.8 Hz,
2H), 4.03 (s, 1H), 3.34 (t, J = 5.4 Hz, 2H), 2.70 (t, J = 6.0 Hz, 2H), 2.14 (s, 3H); 13C NMR (101
MHz, CDCl3) δ 208.02, 146.43, 129.15, 122.07, 114.12, 42.41, 38.51, 30.34; Known compound.8
4-((2-Bromophenyl)amino)butan-2-one 5c was isolated in 71% yield (172.3 mg). Yellow oil;
1H NMR (400 MHz, CDCl3) δ 7.41 (d, J = 7.9 Hz, 1H), 7.17 (t, J = 7.7 Hz, 1H), 6.64 (d, J = 8.1
Hz, 1H), 6.57 (t, J = 7.2 Hz, 1H), 4.56 (s, 1H), 3.46 (dd, J = 11.5, 5.6 Hz, 2H), 2.77 (t, J = 6.3 Hz,
2H), 2.18 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 207.55, 144.68, 132.72, 128.62, 118.11, 111.30,
110.21, 42.67, 38.38, 30.50; Known compound.8
4-((3-Bromophenyl)amino)butan-2-one 6c was isolated in 75% yield (181.8 mg). Yellow oil;
1H NMR (400 MHz, CDCl3) δ 7.00 (t, J = 8.0 Hz, 1H), 6.80 (d, J = 7.8 Hz, 1H), 6.72 (s, 1H), 6.49
(d, J = 8.2 Hz, 1H), 4.10 (s, 1H), 3.37 (t, J = 6.0 Hz, 2H), 2.73 (t, J = 6.0 Hz, 2H), 2.16 (s, 3H);
13C NMR (101 MHz, CDCl3) δ 207.99, 149.16, 130.70, 123.48, 120.42, 115.44, 111.94, 42.46,
38.23, 30.45; Known compound.8
4-((4-Bromophenyl)amino)butan-2-one 7c was isolated in 77% yield (187.3 mg). Yellow oil;
1H NMR (400 MHz, CDCl3) δ 7.23 (d, J = 8.7 Hz, 2H), 6.46 (d, J = 8.7 Hz, 2H), 4.04 (s, 1H),
3.35 (t, J = 6.1 Hz, 2H), 2.71 (t, J = 6.1 Hz, 2H), 2.15 (s, 3H); 13C NMR (101 MHz, CDCl3) δ
208.03, 146.83, 132.07, 114.65, 109.18, 42.42, 38.43, 30.41; Known compound.8
4-((2-Fluorophenyl)amino)butan-2-one 8c was isolated in 40% yield (72.3 mg). Yellow oil;
1H NMR (400 MHz, CDCl3) δ 7.03-6.90 (m, 2H), 6.70 (t, J = 8.0 Hz, 1H), 6.62 (dd, J = 13.2, 8.1
Hz, 1H), 4.17 (s, 1H), 3.43 (t, J = 6.2 Hz, 2H), 2.76 (t, J = 6.3 Hz, 2H), 2.17 (s, 3H); 13C NMR
(101 MHz, CDCl3) δ 207.72, 153.05, 150.68, 136.33 (d, J = 11.6 Hz), 124.69 (d, J = 3.5 Hz),
116.99 (d, J = 7.1 Hz), 114.67 (d, J = 18.4 Hz), 112.17 (d, J = 3.4 Hz), 42.76, 38.12, 30.40; 19F
NMR (377 MHz, CDCl3) δ -136.12 (dd, J = 13.7, 6.2 Hz). Known compound.8
4-((3-Fluorophenyl)amino)butan-2-one 9c was isolated in 50% yield (90.9 mg). Yellow oil;
1H NMR (400 MHz, CDCl3) δ 7.08 (dd, J = 15.0, 8.1 Hz, 1H), 6.36 (dd, J = 17.9, 9.2 Hz, 2H),
6.28 (d, J = 11.6 Hz, 1H), 4.15 (s, 1H), 3.38 (t, J = 5.9 Hz, 2H), 2.74 (t, J = 6.0 Hz, 2H), 2.17 (s,
3H); 13C NMR (101 MHz, CDCl3) δ 208.07, 165.52, 163.11, 149.68 (d, J = 10.9 Hz), 130.51 (d, J
= 10.2 Hz), 109.03 (d, J = 2.2 Hz), 104.18, 103.96, 99.73, 99.47, 42.50, 38.35, 30.44; 19F NMR
(377 MHz, CDCl3) δ -112.80 (dt, J = 10.8, 7.9 Hz). Known compound.9
4-((4-Fluorophenyl)amino)butan-2-one 10c was isolated in 44% yield (79.3 mg). Yellow oil;
1H NMR (400 MHz, CDCl3) δ 6.87 (t, J = 8.3 Hz, 2H), 6.53 (dd, J = 7.8, 3.5 Hz, 2H), 3.88 (s, 1H),
3.35 (t, J = 5.8 Hz, 2H), 2.72 (t, J = 6.0 Hz, 2H), 2.15 (s, 3H); 13C NMR (101 MHz, CDCl3) δ
208.21, 157.23, 154.90, 144.23, 115.93, 115.71, 114.09 (d, J = 7.4 Hz), 42.59, 39.24, 30.40; 19F
NMR (377 MHz, CDCl3) δ -127.72 (tt, J = 7.9, 4.0 Hz). Known compound.8
4-(o-Tolylamino)butan-2-one 11c was isolated in 72% yield (126.9 mg). Yellow oil; 1H NMR
(400 MHz, CDCl3) δ 7.12 (t, J = 7.7 Hz, 1H), 7.05 (d, J = 7.2 Hz, 1H), 6.70-6.59 (m, 2H), 3.90 (s,
1H), 3.47 (t, J = 5.9 Hz, 2H), 2.79 (t, J = 6.1 Hz, 2H), 2.17 (s, 3H), 2.11 (s, 3H); 13C NMR (101
MHz, CDCl3) δ 208.38, 145.80, 130.45, 127.26, 122.73, 117.34, 109.76, 42.76, 38.48, 30.51,
17.62; Known compound.6d
1
4-(m-Tolylamino)butan-2-one 12c was isolated in 79% yield (140.3 mg). Yellow oil; H
14

ACCEPTED MANUSCRIPT
NMR (400 MHz, CDCl3) δ 7.08 (t, J = 7.6 Hz, 1H), 6.56 (d, J = 7.4 Hz, 1H), 6.43 (d, J = 7.7 Hz,
2H), 3.41 (t, J = 6.2 Hz, 2H), 2.74 (t, J = 6.2 Hz, 2H), 2.29 (s, 3H), 2.17 (s, 3H); 13C NMR (101
MHz, CDCl3) δ 208.24, 147.82, 139.16, 129.26, 118.65, 113.93, 110.24, 42.74, 38.47, 30.35,
21.70; Known compound.6d
4-((4-(tert-Butyl)phenyl)amino)butan-2-one 13c was isolated in 92% yield (202.2 mg).
Yellow oil; 1H NMR (400 MHz, CDCl3) δ 7.22 (d, J = 8.6 Hz, 2H), 6.58 (d, J = 8.6 Hz, 2H), 3.89
(s, 1H), 3.41 (t, J = 6.1 Hz, 2H), 2.75 (t, J = 6.1 Hz, 2H), 2.17 (s, 3H), 1.30 (s, 9H); 13C NMR (101
MHz, CDCl3) δ 208.28, 145.46, 140.55, 126.19, 112.90, 42.91, 38.76, 33.97, 31.67, 30.39; Known
compound.8
4-((2-Methoxyphenyl)amino)butan-2-one 14c was isolated in 71% yield (136.7 mg). Yellow
solid; mp: 40-42 °C; 1H NMR (400 MHz, CDCl3) δ 6.76 (t, J = 7.5 Hz, 1H), 6.65 (d, J = 7.6 Hz,
1H), 6.57 (t, J = 7.4 Hz, 1H), 6.51 (d, J = 7.8 Hz, 1H), 4.32 (s, 1H), 3.70 (s, 3H), 3.31 (t, J = 6.4
Hz, 2H), 2.63 (t, J = 6.4 Hz, 2H), 2.04 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 207.80, 147.04,
137.67, 121.20, 116.67, 109.73, 109.52, 55.34, 42.82, 38.06, 30.20. HRMS (ESI) for C11H15NO2,
calcd: 193.1103, found: 197.1100.
4-((3-Methoxyphenyl)amino)butan-2-one 15c was isolated in 74% yield (143.1 mg). Yellow
oil; 1H NMR (400 MHz, CDCl3) δ 7.07 (t, J = 8.1 Hz, 1H), 6.27 (d, J = 8.1 Hz, 1H), 6.21 (d, J =
8.1 Hz, 1H), 6.15 (s, 1H), 3.76 (s, 3H), 3.38 (t, J = 6.1 Hz, 2H), 2.72 (t, J = 6.1 Hz, 2H), 2.14 (s,
3H); 13C NMR (101 MHz, CDCl3) δ 208.19, 160.93, 149.20, 130.12, 106.17, 102.75, 99.01, 55.13,
42.61, 38.38, 30.32. HRMS (ESI) for C11H15NO2, calcd: 193.1103, found: 197.1101.
4-([1,1'-Biphenyl]-4-ylamino)butan-2-one 16c was isolated in 50% yield (118.2 mg). Yellow
oil; 1H NMR (400 MHz, CDCl3) δ 7.44 (d, J = 7.9 Hz, 2H), 7.34 (d, J = 8.4 Hz, 2H), 7.29 (t, J =
7.6 Hz, 2H), 7.15 (dd, J = 13.5, 6.4 Hz, 1H), 6.56 (d, J = 8.4 Hz, 2H), 3.97 (s, 1H), 3.33 (t, J = 6.1
Hz, 2H), 2.63 (t, J = 6.1 Hz, 2H), 2.04 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 208.15, 147.24,
141.24, 130.53, 128.77, 128.07, 126.28 (d, J = 14.6 Hz), 113.33, 42.66, 38.44, 30.39. HRMS (ESI)
for C16H17NO, calcd: 239.1310, found: 239.1313.
4-([1,1'-Biphenyl]-2-ylamino)butan-2-one 17c was isolated in 41% yield (97.2 mg). Yellow
oil; 1H NMR (400 MHz, CDCl3) δ 7.39 (t, J = 7.5 Hz, 2H), 7.35-7.25 (m, 3H), 7.19 (t, J = 7.7 Hz,
1H), 7.05 (d, J = 7.4 Hz, 1H), 6.73 (t, J = 7.4 Hz, 1H), 6.66 (d, J = 8.1 Hz, 1H), 4.12 (s, 1H), 3.35
(t, J = 6.4 Hz, 2H), 2.63 (t, J = 6.4 Hz, 2H), 2.06 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 207.73,
144.61, 139.38, 130.52, 129.38, 129.01, 128.80, 128.22, 127.38, 117.29, 110.45, 42.73, 38.55,
30.38; Known compound.8
4-((3-(Trifluoromethyl)phenyl)amino)butan-2-one 18c was isolated in 42% yield (97.3 mg).
Yellow oil; 1H NMR (400 MHz, CDCl3) δ 7.14 (t, J = 7.9 Hz, 1H), 6.83 (d, J = 7.6 Hz, 1H), 6.69
(s, 1H), 6.63 (d, J = 8.2 Hz, 1H), 4.19 (s, 1H), 3.32 (t, J = 6.0 Hz, 2H), 2.64 (t, J = 6.0 Hz, 2H),
2.07 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 208.02, 148.11, 132.11, 131.79, 131.48, 131.16,
129.80, 128.53, 125.83, 123.12, 120.42, 116.10, 113.92 (q, J = 3.8 Hz), 108.96 (q, J = 3.8 Hz),
42.35, 38.17, 30.29; 19F NMR (377 MHz, CDCl3) δ -62.89. Known compound.8
4-((4-(Trifluoromethyl)phenyl)amino)butan-2-one 19c was isolated in 45% yield (103.8 mg).
Yellow oil; 1H NMR (400 MHz, CDCl3) δ 7.39 (d, J = 8.5 Hz, 2H), 6.58 (d, J = 8.5 Hz, 2H), 4.37
(s, 1H), 3.44 (t, J = 6.0 Hz, 2H), 2.75 (t, J = 6.0 Hz, 2H), 2.17 (s, 3H); 13C NMR (101 MHz,
CDCl3) δ 207.97, 150.40, 126.88 (q, J = 3.7 Hz), 126.51, 123.83, 112.14, 42.44, 37.99, 30.50; 19
F
NMR (377 MHz, CDCl3) δ -61.01. HRMS (ESI) for C11H12F3NO, calcd: 231.0871, found:
231.0872.
15

ACCEPTED MANUSCRIPT
4-((2-Nitrophenyl)amino)butan-2-one 20c was isolated in 38% yield (79.9 mg). Yellow solid;
1
mp: 63-65 °C; H NMR (400 MHz, CDCl3) δ 8.13 (d, J = 8.6 Hz, 1H), 8.06 (s, 1H), 7.43 (t, J =
7.8 Hz, 1H), 6.85 (d, J = 8.6 Hz, 1H), 6.64 (t, J = 7.8 Hz, 1H), 3.59 (q, J = 6.5 Hz, 2H), 2.86 (t, J
= 6.7 Hz, 2H), 2.20 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 206.43, 145.21, 136.42, 132.26,
127.11, 115.63, 113.57, 42.60, 37.45, 30.46. HRMS (ESI) for C10H12N2O3, calcd: 208.0848, found:
208.0843.
4-((3-Nitrophenyl)amino)butan-2-one 21c was isolated in 49% yield (101.6 mg). Yellow oil;
1H NMR (400 MHz, CDCl3) δ 7.34 (d, J = 7.8 Hz, 1H), 7.22 (s, 1H), 7.11 (t, J = 7.9 Hz, 1H), 6.73
(d, J = 7.6 Hz, 1H), 4.38 (s, 1H), 3.39-3.27 (m, 2H), 2.66 (t, J = 5.8 Hz, 2H), 2.06 (s, 3H); 13C
NMR (101 MHz, CDCl3) δ 207.94, 149.48, 148.79, 129.88, 119.13, 112.00, 106.24, 42.23, 38.18,
30.39. HRMS (ESI) for C10H12N2O3, calcd: 208.0848, found: 208.0847.
4-((4-Nitrophenyl)amino)butan-2-one 22c was isolated in 82% yield (117.3 mg). Yellow solid;
1
mp: 89-91 °C; H NMR (400 MHz, CDCl3) δ 8.00 (d, J = 9.0 Hz, 2H), 6.49 (d, J = 9.2 Hz, 2H),
5.12 (s, 1H), 3.47 (q, J = 5.9 Hz, 2H), 2.78 (t, J = 6.0 Hz, 2H), 2.16 (s, 3H); 13C NMR (101 MHz,
CDCl3) δ 207.58, 153.22, 137.76, 126.50, 111.07, 42.14, 37.69, 30.32; Known compound.8
2-((3-Oxobutyl)amino)benzonitrile 23c was isolated in 78% yield (146.7 mg). Yellow oil; 1H
NMR (400 MHz, CDCl3) δ 7.25 (d, J = 5.8 Hz, 2H), 6.56 (dd, J = 8.3, 4.9 Hz, 2H), 4.82 (s, 1H),
3.44-3.33 (m, 2H), 2.70 (d, J = 3.7 Hz, 2H), 2.09 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 207.07,
149.86, 134.19, 132.77, 117.72, 116.52, 110.45, 95.79, 42.19, 37.61, 30.19; Known compound.8
4-((3-Oxobutyl)amino)benzonitrile 24c was isolated in 77% yield (145.2 mg). Yellow solid;
1
mp: 91-93 °C; H NMR (400 MHz, CDCl3) δ 7.37 (d, J = 8.8 Hz, 2H), 6.52 (d, J = 8.8 Hz, 2H),
4.68 (s, 1H), 3.42 (t, J = 6.0 Hz, 2H), 2.74 (t, J = 6.0 Hz, 2H), 2.16 (s, 3H); 13C NMR (101 MHz,
CDCl3) δ 207.62, 151.04, 133.81, 120.54, 112.29, 98.71, 42.21, 37.54, 30.38; Known compound.8
Methyl 2-((3-oxobutyl)amino)benzoate 25c was isolated in 64% yield (141.0 mg). Yellow oil;
1H NMR (400 MHz, CDCl3) δ 7.39 (d, J = 8.0 Hz, 1H), 7.26 (s, 1H), 6.85 (t, J = 8.5 Hz, 1H), 6.19
(d, J = 8.5 Hz, 1H), 6.09 (t, J = 7.5 Hz, 1H), 3.34 (s, 3H), 2.99 (dd, J = 12.5, 6.6 Hz, 2H), 2.29 (t, J
= 6.7 Hz, 2H), 1.68 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 207.03, 168.93, 150.69, 134.65,
131.76, 114.74, 110.96, 110.21, 51.48, 42.83, 37.33, 30.29; Known compound.9
Methyl 4-((3-oxobutyl)amino)benzoate 26c was isolated in 87% yield (192.1 mg). Yellow
solid; mp: 108-110 °C; 1H NMR (400 MHz, CDCl3) δ 7.82 (d, J = 8.7 Hz, 2H), 6.51 (d, J = 8.8 Hz,
2H), 4.57 (s, 1H), 3.81 (s, 3H), 3.42 (dd, J = 11.3, 5.5 Hz, 2H), 2.72 (t, J = 6.0 Hz, 2H), 2.13 (s,
3H); 13C NMR (101 MHz, CDCl3) δ 207.75, 167.33, 151.60, 131.64, 118.45, 111.55, 51.58, 42.38,
37.69, 30.33; Known compound.8
4-((4-(Methylsulfonyl)phenyl)amino)butan-2-one 27c was isolated in 59% yield (125.7 mg).
Colourless solid; mp: 79-81 °C; 1H NMR (400 MHz, CDCl3) δ 7.63 (d, J = 8.5 Hz, 2H), 6.57 (d, J
= 6.0 Hz, 2H), 4.83 (s, 1H), 3.41 (d, J = 4.8 Hz, 2H), 2.95 (s, 3H), 2.73 (d, J = 5.5 Hz, 2H), 2.13 (s,
3H); 13C NMR (101 MHz, CDCl3) δ 207.62, 152.05, 129.32, 127.02, 111.80, 45.04, 42.13, 37.56,
30.31; Known compound.8
4-((2-Bromo-4-chlorophenyl)amino)butan-2-one 28c was isolated in 76% yield (209.7 mg).
Yellow oil; 1H NMR (400 MHz, CDCl3) δ 7.35 (s, 1H), 7.09 (d, J = 8.7 Hz, 1H), 6.50 (d, J = 8.7
Hz, 1H), 4.54 (s, 1H), 3.36 (s, 2H), 2.72 (t, J = 5.7 Hz, 2H), 2.14 (s, 3H); 13C NMR (101 MHz,
CDCl3) δ 207.30, 143.41, 131.80, 128.34, 121.48, 111.58, 109.79, 42.27, 38.33, 30.31. HRMS
(ESI) for C10H11BrClNO, calcd: 274.9713, found: 274.9712.
4-((2-Bromo-4-methylphenyl)amino)butan-2-one 29c was isolated in 84% yield (215.7 mg).
16

ACCEPTED MANUSCRIPT
Colourless oil; 1H NMR (400 MHz, CDCl3) δ 7.13 (s, 1H), 6.87 (d, J = 8.2 Hz, 1H), 6.45 (d, J =
8.2 Hz, 1H), 4.29 (s, 1H), 3.30 (s, 2H), 2.63 (t, J = 6.3 Hz, 2H), 2.10 (s, 3H), 2.04 (s, 3H); 13C
NMR (101 MHz, CDCl3) δ 207.53, 142.34, 132.89, 129.04, 127.54, 111.35, 110.00, 42.53, 38.56,
30.29, 20.00. HRMS (ESI) for C11H14BrNO, calcd: 255.0259, found:255.0261.
4-((2-Bromo-3-methylphenyl)amino)butan-2-one 30c was isolated in 90% yield (231.0 mg).
Yellow oil; 1H NMR (400 MHz, CDCl3) δ 7.08 (t, J = 7.8 Hz, 1H), 6.61 (d, J = 7.4 Hz, 1H), 6.49
(d, J = 8.1 Hz, 1H), 4.68 (s, 1H), 3.44 (d, J = 5.1 Hz, 2H), 2.75 (t, J = 6.4 Hz, 2H), 2.37 (s, 3H),
2.16 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 207.49, 144.70, 138.55, 127.65, 119.19, 112.71,
108.59, 42.52, 38.47, 30.28, 23.79; Known compound.8
4-((3-Chloro-4-fluorophenyl)amino)butan-2-one 31c was isolated in 80% yield (172.7 mg).
Yellow oil; 1H NMR (400 MHz, CDCl3) δ 6.90 (t, J = 8.9 Hz, 1H), 6.56 (dd, J = 6.0, 2.8 Hz, 1H),
6.39 (dt, J = 8.7, 3.2 Hz, 1H), 3.30 (t, J = 6.0 Hz, 2H), 2.70 (t, J = 6.0 Hz, 2H), 2.15 (s, 3H); 13
C
NMR (101 MHz, CDCl3) δ 208.04, 152.19, 149.83, 144.89, 121.10 (d, J = 18.3 Hz), 117.05,
116.83, 113.89, 112.47 (d, J = 6.3 Hz), 42.32, 38.85, 30.34; 19F NMR (377 MHz, CDCl3) δ
-131.04. Known compound.8
4-((3,4-Dichlorophenyl)amino)butan-2-one 32c was isolated in 93% yield (215.5 mg).
Yellow oil; 1H NMR (400 MHz, CDCl3) δ 7.14 (d, J = 5.9 Hz, 1H), 6.62 (s, 1H), 6.39 (d, J = 8.7
Hz, 1H), 4.14 (s, 1H), 3.33 (d, J = 5.9 Hz, 2H), 2.71 (d, J = 3.2 Hz, 2H), 2.15 (s, 3H); 13C NMR
(101 MHz, CDCl3) δ 207.93, 147.45, 132.87, 130.74, 119.82, 113.88, 112.88, 42.28, 38.33, 30.40;
Known compound.8
4-((4-Bromo-2-chlorophenyl)amino)butan-2-one 33c was isolated in 85% yield (235.6 mg).
Yellow oil; 1H NMR (400 MHz, CDCl3) δ 7.31 (s, 1H), 7.17 (d, J = 6.2 Hz, 1H), 6.48 (d, J = 8.1
Hz, 1H), 4.55 (s, 1H), 3.36 (s, 2H), 2.75-2.64 (m, 2H), 2.13 (s, 3H); 13C NMR (101 MHz, CDCl3)
δ 207.27, 142.81, 131.35, 130.56, 119.95, 112.09, 107.63, 42.26, 38.01, 30.28; Known
compound.8
4-((3,5-Dimethylphenyl)amino)butan-2-one 34c was isolated in 86% yield (165.1 mg).
Colourless oil; 1H NMR (400 MHz, CDCl3) δ 6.29 (s, 1H), 6.16 (s, 2H), 3.30 (t, J = 6.2 Hz, 2H),
2.63 (t, J = 6.1 Hz, 2H), 2.15 (s, 6H), 2.06 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 208.24, 147.87,
139.01, 119.72, 111.07, 42.80, 38.49, 30.32, 21.57; Known compound.8
4-(Quinolin-8-ylamino)butan-2-one 35c was isolated in 51% yield (109.6 mg). Brown oil; 1H
NMR (400 MHz, CDCl3) δ 8.68 (d, J = 2.7 Hz, 1H), 8.01 (d, J = 8.2 Hz, 1H), 7.36 (t, J = 7.9 Hz,
1H), 7.31 (dd, J = 8.2, 4.2 Hz, 1H), 7.03 (d, J = 8.1 Hz, 1H), 6.67 (d, J = 7.6 Hz, 1H), 6.28 (s, 1H),
3.59 (t, J = 6.6 Hz, 2H), 2.83 (t, J = 6.6 Hz, 2H), 2.14 (s, 3H); 13C NMR (101 MHz, CDCl3) δ
207.49, 146.93, 144.35, 138.28, 135.94, 128.67, 127.71, 121.43, 114.12, 104.56, 42.77, 37.88,
30.30. HRMS (ESI) for C13H14N2O, calcd: 214.1106, found:214.1110.
4-(Methyl(p-tolyl)amino)butan-2-one 36c was isolated in 37% yield (71.1 mg). Yellow oil;
1H NMR (400 MHz, CDCl3) δ 7.08 (d, J = 8.4 Hz, 2H), 6.67 (d, J = 8.5 Hz, 2H), 3.62 (t, J = 7.0
Hz, 2H), 2.91 (s, 3H), 2.70 (t, J = 7.0 Hz, 2H), 2.29 (s, 3H), 2.17 (s, 3H); 13C NMR (101 MHz,
CDCl3) δ 208.21, 146.78, 129.89, 126.15, 113.11, 47.76, 40.23, 38.74, 30.65, 20.30; Known
compound.9
1
4-Methylbenzo[h]quinoline 37c was isolated in 51% yield (98.1 mg). Brown oil; H NMR
(400 MHz, CDCl3) δ 9.21 (d, J = 8.1 Hz, 1H), 8.74 (d, J = 4.5 Hz, 1H), 7.82-7.65 (m, 3H), 7.60
(dt, J = 21.4, 7.4 Hz, 2H), 7.21 (s, 1H), 2.60 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 148.54,
146.27, 144.20, 133.44, 131.98, 128.13, 127.82, 127.47, 127.15, 126.02, 124.88, 123.11, 121.45,
17

ACCEPTED MANUSCRIPT
19.17; Known compound.9
6-Bromo-4-methylbenzo[h]quinoline 38c was isolated in 50% yield (135.8 mg). Gray oil; 1H
NMR (400 MHz, CDCl3) δ 9.29 (dd, J = 6.2, 3.1 Hz, 1H), 8.77 (d, J = 4.4 Hz, 1H), 8.26 (dd, J =
5.7, 3.5 Hz, 1H), 8.09 (s, 1H), 7.74 (dd, J = 6.1, 3.3 Hz, 2H), 7.23 (d, J = 4.3 Hz, 1H), 2.59 (s, 3H);
13C NMR (101 MHz, CDCl3) δ 148.74, 145.40, 143.42, 132.75, 131.69, 129.02, 127.90, 127.39,
126.27, 125.16 (d, J = 7.1 Hz), 123.45, 122.58, 18.98. HRMS (ESI) for C14H10BrN, calcd:
270.9997, found: 270.9992.
Phenyl-3-(phenylamino)propan-1-one 39c was isolated in 71% yield (160.0 mg). White solid;
1
mp: 93-95 °C; H NMR (400 MHz, CDCl3) δ 7.95 (d, J = 7.3 Hz, 2H), 7.57 (t, J = 7.4 Hz, 1H),
7.46 (t, J = 7.6 Hz, 2H), 7.18 (t, J = 7.9 Hz, 2H), 6.71 (t, J = 7.3 Hz, 1H), 6.65 (d, J = 7.8 Hz, 2H),
4.12 (s, 1H), 3.63 (t, J = 6.1 Hz, 2H), 3.29 (t, J = 6.1 Hz, 2H); 13C NMR (101 MHz, CDCl3) δ
199.49, 147.89, 136.90, 133.53, 129.52, 128.85, 128.21, 117.77, 113.22, 38.87, 37.84. HRMS
(ESI) for C15H15NO, calcd: 225.1154, found: 225.1164.
3-((4-Chlorophenyl)amino)-1-phenylpropan-1-one 40c was isolated in 77% yield (200.0 mg).
White solid; mp: 126-127 °C; 1H NMR (400 MHz, CDCl3) δ 7.95 (d, J = 7.3 Hz, 2H), 7.58 (t, J =
7.4 Hz, 1H), 7.47 (t, J = 7.6 Hz, 2H), 7.12 (d, J = 8.8 Hz, 2H), 6.56 (d, J = 8.8 Hz, 2H), 4.16 (s,
1H), 3.58 (t, J = 6.0 Hz, 2H), 3.27 (t, J = 6.0 Hz, 2H); 13C NMR (101 MHz, CDCl3) δ 199.31,
146.49, 136.79, 133.63, 129.31, 128.88, 128.19, 122.28, 114.28, 38.99, 37.58. HRMS (ESI) for
C15H14ClNO, calcd: 259.0764, found: 259.0754.
3-((3-Methoxyphenyl)amino)-1-phenylpropan-1-one 41c was isolated in 81% yield (207.0
mg). White solid; mp: 75-77 °C; 1H NMR (400 MHz, CDCl3) δ 7.95 (d, J = 7.3 Hz, 2H), 7.57 (t, J
= 7.4 Hz, 1H), 7.46 (t, J = 7.6 Hz, 2H), 7.08 (t, J = 8.1 Hz, 1H), 6.27 (t, J = 7.2 Hz, 2H), 6.20 (s,
1H), 4.16 (s, 1H), 3.77 (s, 3H), 3.61 (t, J = 6.0 Hz, 2H), 3.28 (t, J = 6.0 Hz, 2H); 13C NMR (101
MHz, CDCl3) δ 199.47, 161.08, 149.29, 136.88, 133.53, 130.25, 128.84, 128.21, 106.33, 102.84,
99.14, 55.27, 38.83, 37.79. HRMS (ESI) for C16H17NO2, calcd: 255.1259, found: 255.1260.
Conflict of Interest The authors declare that they have no conflict of interest.
1
Supporting Information Available H NMR, 13C NMR and 19C NMR spectras for all new
compounds and control experiments. This material is available free of charge via the internet at
http://XXX.XXX.XXX.
Acknowledgments We gratefully acknowledge the research foundation of weifang medical
university, innovative drug research and development center of weifang medical university and the
natural science foundation of shandong province (No. ZR2018LH017) for support of this research.
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