PTSA-catalyzed one-pot synthesis of quinoxalines using DMSO as the oxidant

Article abstract of DOI:10.1080/00397911.2016.1213297

An efficient p-toluene sulfonic acid–catalyzed, one-pot, two-step oxidative system for cyclization of o-diaminobenzene with 1,2-diaryl-2-hydroxyethanone to quinoxalines was described. A nontoxic, readily available oxidant, dimethylsulfoxide (DMSO), was applied in this process. A broad range of substrates was applied to this method, and target compounds were obtained with good yields.

Full text of DOI:10.1080/00397911.2016.1213297

Synthetic Communications
An International Journal for Rapid Communication of Synthetic Organic
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PTSA-Catalyzed One-Pot Synthesis of Quinoxalines
Using DMSO as the Oxidant
Zeyuan Zhang, Caixia Xie, Lei Feng & Chen Ma
To cite this article: Zeyuan Zhang, Caixia Xie, Lei Feng & Chen Ma (2016): PTSA-Catalyzed One-
Pot Synthesis of Quinoxalines Using DMSO as the Oxidant, Synthetic Communications, DOI:
10.1080/00397911.2016.1213297
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Date: 22 August 2016, At: 03:19

PTSA-catalyzed One-pot Synthesis of Quinoxalines Using DMSO as the Oxidant
Zeyuan Zhang1, Caixia Xie1, Lei Feng1, Chen Ma1,2
1School of Chemistry and Chemical Engineering, Shandong University, Jinan, P R China,
2State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Insti-
tute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medi-
cal College, Beijing, P. R. China
Corresponding author: E-mail: chenma@sdu.edu.cn
Abstract
An efficient PTSA catalyzed one-pot two-step oxidative system for cyclization of o-
diaminobenzene with 1,2-diaryl-2-hydroxyethanone to quinoxalines was described. A
nontoxic, readily available oxidant–DMSO was applied in this process. A broad range of
substrates were applied to this method, and target compounds were obtained with good
yields.
GRAPHICAL ABSTRACT
1

KEYWORDS: quinoxalines, PTSA-catalyzed, oxidant–DMSO, one-pot, transition met-
al-free, tandem process
INTRODUCTION
Quinoxaline derivatives are an important class of nitrogen-containing heterocyclic com-
pounds and play an important role in pharmaceutical chemistry for their bioactivities,
such as antiviral,1 antibacterial,2 anti-inflammatory,3 anticancer and anthelmintic.4 Fur-
thermore, quinoxalines have been reported to be biocides,5 dyes,6 efficient electrolumi-
nescent materials,7 pharmaceuticals,8 and organic semiconductors.9
Many synthetic strategies have been reported for the preparation of substituted
quinoxalines.10 However, most of these methods suffer from expensive and detrimental
metal precursors, harsh reaction conditions, critical product isolation procedures and un-
satisfactory product yields which limit their use in green chemistry.
Since DMSO as Oxidant was first reported in 1956,11 it has received significant attention.
From previous literature, DMSO can act as an inexpensive, nontoxic, readily available
oxidant for various organic transformations under mild and convenient conditions.12
However, there is no example of quinoxaline synthesis using DMSO as oxidant.
2

Initially, we expected to isolate 2,4,5-triphenyloxazole from the cyclization reaction of
benzoin with benzamide catalyzed by PTSA (p-toluene sulfonic acid, TsOH·H2O) in air
atmosphere. Unexpectedly, benzil was obtained in a good yield (Scheme 1).
In the beginning, we assumed that benzil was generated by the oxidation of benzoin in
air. However, benzil was still obtained in the presence of PTSA and DMSO under N2
(Scheme 2). Kornblum reported that benzyl p-toluenesulfonate can be oxidized to
benzaldehyde by DMSO. 11 Therefore, we eventually determined that benzil was obtained
from p-toluenesulfonate intermediate by DMSO oxidation (Scheme 3, a and b).
Yao reported that Lewis acids catalyzed the cyclization of o-diaminobenzene with benzil
to afford quinoxaline.15a Therefore, we carried out a one-pot two-step cyclization reaction
of o-diaminobenzene with 1,2-diaryl-2-hydroxyethanone to afford the corresponding
quinoxalines; 2,3-diphenylquinoxaline was obtained in a good yield (Scheme 3, c).
We have been focusing on the direct synthesis of heterocyclic systems using tandem reac-
tions.13 In this paper, we developed an efficient PTSA-catalyzed one-pot two-step oxida-
tion reaction for the cyclization of o-diaminobenzene with 1,2-diaryl-2-hydroxyethanone
to afford the corresponding quinoxalines.
3

RESULTS AND DISCUSSION
Although 2,3-diphenylquinoxaline was obtained in a good yield by the abovementioned
method, the optimum condition for this reaction were determined. The results are summa-
rized in Table 1.
First, several solvents were investigated under N2 atmosphere, no product was detected
until DMSO was used (Table 1, entries 1-6). Based on this result, several sulfonic acids
such as TsOH, MSA (methanesulfonic acid), and TfOH (trifluoromethanesulfonic acid)
were screened for the reaction. MSA and TfOH showed the same catalytic activity as
TsOH (Table 1, entries 6-8). However, TfOH was selected as the catalyst for its low price.
Furthermore, 3a was not obtained without adding acid (Table 1, entry 9). The amount of
TsOH was also investigated; 50 mol% TsOH resulted in the highest yield of 90% (Table
1, entries 6 and 10-12). A low yield (3a) was obtained when 1a and 2a were added simul-
taneously (Table 1, entry 13). Further, air had no significant effect on the reaction (Table
1, entry 14).
With the optimized conditions in hand, the substrate scope of this reaction was investi-
gated and the results are summarized in Table 2. In the presence of electron-donating sub-
stituents on the amine part, the yields of the products increased. Low yields were ob-
tained when electron- withdrawing substituents were present on the amine except 3ae. In
4

contrast, electron-donating substituents on the aromatic ring attached to hydroxy ketones
decreased the product yields and reversed the trend observed with the electron-
withdrawing groups. Interestingly, considerable yields were obtained when nitro substitu-
ents group were present on the amines (3ae, 3be, 3ce, 3de and 3ee). Previous studies ei-
ther did not achieve this result14 or attempt this reaction15. The presence of an electron-
donating group in hydroxy ketones may hinder the nucleophilic attack on the in situ
formed dicarbonyl, leading to a lower yield. On the other hand, an electron-withdrawing
substituent on the hydroxy ketone part resulted in a shorter reaction time in the oxidation
process (Table 2, entries 20-23). Over all, both the catalyst and oxidant showed excep-
tionally high reactivity towards this reaction.
To gain some insights into the mechanism of the reaction, several control experiments
were carried out (Scheme 5). Possible intermediate 1aa was observed to react with 2a to
generate 3aa in good yield without TsOH. The target molecule 3aa was also obtained
from possible intermediate 1ac reacting with 2a in the presence of TsOH.
Based on the above experiments, the possible mechanism for this reaction can be illus-
trated in Scheme 6. Firstly, the dehydration of benzion 1a and PTSA could generate sul-
fonic acid ester 1aa. And secondly, sulfonic acid ester 1aa could be oxidized to benzyl
5

1ac by DMSO. In the end, PTSA could catalyze the cyclization of benzyl with diamine to
quinoxaline.
CONCLUSIONS
A variety of quinoxaline derivatives were synthesized by cyclization of o-
diaminobenzene with 1,2-diaryl-2-hydroxyethanone using PTSA as catalyst and DMSO
as oxidant. Quinoxalines were obtained in good yields and this methodology applied to a
broad range of substrates. Further studies on the application of this procedure to the syn-
thesis of pharmaceutical compounds are in progress.
EXPERIMENTAL SECTION
Reagents were commercially available and were used without further purification. All
reactions were monitored by thin-layer chromatography (TLC). 1H NMR spectra were
recorded on a Bruker Avance 400 or 300 spectrometer at 400 or 300 MHz, using CDCl3
or DMSO-d6 as solvent and tetramethylsilane (TMS) as internal standard. 13C NMR spec-
tra were run in the same instrument at 100 or 75 MHz. Melting points were determined
on an XD-4 digital micro melting point apparatus. HRMS spectra were determined on a
Q-TOF6510 spectrograph (Agilent).
General Procedure For The Synthesis Of Compounds 3
6

A mixture of 1,2-diaryl-2-hydroxyethanone 1 (1.0 mmol), PTSA (0.5 mmol) in DMSO (2
mL) was heated to 100 oC (TLC monitored). Then the mixture was added in o-
diaminobenzene 2 (1 mmol), and stirred for 1 h. Then the mixture was cooled to room
temperature and diluted with brine (30 mL) and extracted with dichloromethane twice (2
× 30 mL). The combined organic layers were dried with MgSO4 and the solvent was re-
moved in vacuo to afford a residue. The residue was purified by column chromatography
to afford 3.
2,3-Diphenylquinoxaline (3aa).
White solid. 1H NMR (300 M, DMSO-d6): δ 8.19-8.14 (2H, m), 7.95-7.81 (2H, m), 7.50-
7.47 (4H, m), 7.45-7.33 (6H, m); 13C NMR (75 MHz, DMSO-d6): δ 153.04，140.43,
138.75, 130.38, 129.66, 129.55, 129.47, 128.78, 128.73, 128.01; HRMS calcd for
C20H14N2 (M+H)+ 283.1230; found: 283.1232.
6-Methyl-2,3-Diphenylquinoxaline (3ab).
White solid. 1H NMR (300 M, DMSO-d6): δ 8.04 (1H, J = 8.4 Hz, d), 7.94 (1H, s), 7.71
(2H, J = 8.4, 1.8 Hz, dd), 7.48-7.45 (4H, m), 7.43-7.32 (6H, m), 2.59 (3H, s); 13C NMR
(75 MHz, DMSO-d6): δ 152.82, 152.08, 140.52, 140.50, 138.92, 138.85, 132.52, 129.63,
128.64, 128.57, 128.32, 127.98, 127.47, 21.32; HRMS calcd for C21H16N2 (M+H)+
297.1386; found: 297.1391.
7

6,7-Dimethyl-2,3-Diphenylquinoxaline (3ac).
White solid. 1H NMR (300 M, CDCl3): δ 7.92 (2H, s), 7.511-7.47 (4H, m), 7.35-7.26 (6H,
m), 2.52 (6H, s); 13C NMR (75 MHz, CDCl3 ): δ 152.50, 140.53, 140.22, 139.38, 129.86,
128.53, 128.22, 128.19, 20.42; HRMS calcd for C22H18N2 (M+H)+ 311.1543; found:
311.1550.
6-Chloro-2,3-Diphenylquinoxaline (3ad).
White solid. 1H NMR (300 M, DMSO-d6): δ 8.25 (1H, J = 2.1 Hz, d), 8.19 (1H, J =9.0
Hz), 7.92 (1H, J = 2.1, 9.0 Hz, dd), 7.50-7.35 (10H, m); 13C NMR (75 MHz, DMSO-d6):
δ 154.04, 153.45, 140.76, 139.10, 138.39, 138.33, 134.60, 130.94, 129.68, 129.65, 129.00,
128.04, 127.48; HRMS calcd for C20H13ClN2 (M+H)+ 317.0840; found: 317.0851.
6-Nitro-2,3-Diphenylquinoxaline (3ae).
Yellow solid. 1H NMR (300 M, DMSO-d6): δ 8.95 (1H, J = 1.8 Hz, d), 8.57 (1H, J = 1.8,
9.0 Hz, dd), 8.38 (1H, J = 9.3 Hz, d), 7.54-7.52 (4H, m), 7.48-7.37 (6H, m); 13C NMR
(75 MHz, DMSO-d6): δ 156.04, 155.38, 147.64, 142.98, 139.21, 137.97, 137.94, 130.94,
129.79, 129.71, 129.5, 129.36, 128.13, 124.83, 123.57; HRMS calcd for C20H13N3O2
(M+H)+ 328.1081; found: 328.1083.
2,3-Di-P-Tolylquinoxaline (3ba).
8

White solid. 1H NMR (300 M, DMSO-d6): δ 8.16-8.10 (2H, m), 7.89-7.83 (2H, m), 7.39
(4H, J = 8.1 Hz, d), 7.18 (4H, J = 7.8 Hz, d), 2.33 (6H, s); 13C NMR (75 MHz, DMSO-
d6): δ 152.93, 140.34, 138.27, 136.04, 130.14, 129.56, 128.68, 128.64, 20.81; HRMS
calcd for C22H18N2(M+H)+ 311.1543; found: 311.1542.
6-Methyl-2,3-Di-P-Tolylquinoxaline (3bb).
White solid. 1H NMR (300 M, CDCl3): δ 8.04 (1H, J = 8.4 Hz, d), 7.93 (1H, s), 7.57 (1H,
J = 8.4, 1.8 Hz, dd), 7.41 (4H, J = 1.2, 7.8 Hz, dd), 7.13 (4H, J = 7.8 Hz, d), 2.60 (3H, s),
2.36 (6H, s); 13C NMR (75 MHz, CDCl3): δ 153.30, 152.59, 141.14, 140.18, 139.59,
138.65, 138.57,136.47, 132.02, 129.74, 129.71, 128.94, 128.60, 127.92, 21.87, 21.83;HR
MS calcd for C23H20N2 (M+H)+ 325,1699; found: 325.1699.
6,7-Dimethyl-2,3-Di-P-Tolylquinoxaline (3bc).
White solid. 1H NMR (300 M, CDCl3): δ 7.89 (2H, s), 7.40 (4H, J = 8.1 Hz, d), 7.13 (4H,
13
J = 8.1 Hz, d), 2.50 (6H, s), 2.360 (6H, s); C NMR (75 MHz, CDCl3): δ 152.49, 140.19,
140.09, 138.43, 136.63, 129.73, 128.90, 128.13, 21.32, 20.37; HRMS calcd for C24H22N2
(M+H)+ 339.1856; found: 339.1847.
6-Nitro-2,3-Di-P-Tolylquinoxaline (3be).
9

1
Yellow solid. H NMR (300 M, CDCl3): δ 9.40 (1H, J = 2.7 Hz, d), 8.49 (1H, J = 2.4,
9.0 Hz, dd), 8.25 (1H, J = 9.0 Hz, d), 7.49-7.45 (4H, m), 7.26-7.17 (4H, m), 2.39 (6H, s);
13C NMR (75 MHz, CDCl3 ): δ 156.32, 155.70, 147,71, 143.56, 140.02, 139.88, 139.83,
135.44, 135.38, 130.61, 129.84, 129.74, 129.18, 125.54, 123.03, 21.42; HRMS calcd for
C22H17N3O2 (M+H)+ 356.1394; found: 356.1390.
2,3-Bis(4-Methoxyphenyl)Quinoxaline (3ca).
White solid. 1H NMR (300 M, CDCl3): δ 8.17-8.12 (2H, m), 7.76-7.70 (2H, m), 7.52-
7.48 (4H, m), 7.26-6.85 (4H, m), 3.84 (6H, s); 13C NMR (75 MHz, CDCl3 ): δ 160.24,
152.99, 140.96, 131.57, 131.28, 129.61, 128.94, 113.81, 55.31; HR MS calcd for
C22H18N202 (M+H)+ 343.1441; found: 343.1442.
2,3-Bis(4-Methoxyphenyl)-6-Methylquinoxaline (3cb).
White solid. 1H NMR (300 M, CDCl3): δ 8.02 (1H, J = 8.4 Hz, d), 7.92 (1H, s), 7.56 (1H,
J = 1.8, 8.7 Hz, dd), 7.51-7.45 (4H, m), 6.89-6.85 (4H, m), 3.83 (6H, s), 2.60 (3H, s); 13C
NMR (75 MHz, CDCl3): δ 160.16, 160.09, 152.81, 152.12, 140.99, 140.11, 139.46,
131.93, 131.75, 131.70, 131.27, 131.22, 128.47, 127.78, 113.76, 55.30; HRMS calcd for
C23H20N2O2 (M+H)+ 357.1598; found: 357.1587.
2,3-Bis(4-Methoxyphenyl)-6,7-Dimethylquinoxaline (3cc).
10

White solid. 1H NMR (300 M, CDCl3): δ 7.89 (2H, s), 7.49-7.44 (4H, m), 6.89-6.84 (4H,
m), 3.83 (6H, s), 2.50 (6H, s); 13C NMR (75 MHz, CDCl3): δ 159.98, 152.08, 140.06,
140.00, 132.09, 131.22, 128.10, 113.72, 55.31; HRMS calcd for C24H22N2O2 (M+H)+
371.1754; found: 371.1756.
6-Chloro-2,3-Bis(4-Methoxyphenyl)Quinoxaline (3cd).
White solid. 1H NMR (300 M, CDCl3): δ 8.13 (1H, J = 2.1 Hz, d), 8.07 (1H, J = 9.0Hz,
d), 7.66 (1H, J = 2.4, 9.0 Hz, dd), 7.51-7.47 (4H, m), 6.90-6.85 (4H, m), 3.837 (6H, s);
13C NMR (75 MHz, CDCl3): δ 160.49, 160.42, 153,79,153.11,141.24, 139.42, 135.24,
131.32, 131.25, 131.20,131.13, 130.55, 130.13, 127.82, 113.86,55.33; HRMS calcd for
C22H17ClN2O2 (M+H)+ 377.1051; found: 377.1050.
2,3-Bis(4-Methoxyphenyl)-6-Nitroquinoxaline (3ce).
Yellow solid. 1H NMR (300 M, CDCl3): δ 9.02 (1H, J = 2.4 Hz, d), 8.48 (1H, J = 2.4, 9.0
Hz, dd), 8.24 (1H, J = 9.0Hz, d), 7.59-7.52 (4H, m), 6.92-6.89 (4H, t), 3.86 (6H, s); 13C
NMR (75 MHz, CDCl3): δ 161.02, 160.87, 155.75, 155.17, 147.58, 143.46, 139.75,
131.50, 131.34, 130.64, 130.39, 125.39, 122.87, 113.98, 55.37; HRMS calcd for
C22H17N3O4 (M+H)+ 388.1292; found: 388.1393.
2,3-Di(Furan-2-Yl)Quinoxaline (3da).
11

Gray solid. 1H NMR (300 M, DMSO-d6): δ 8.14-8.08 (1H, m), 7.92-7.86 (4H, m), 6.74-
6.72 (4H, m); 13C NMR (75 MHz, DMSO-d6): δ 150.31, 144.91, 142.07, 139.92, 130.90,
128.68, 112.85, 112.15; HRMS calcd for C16H10N2O2 (M+H)+ 263.0815; found:
263.0827.
2,3-Di(Furan-2-Yl)-6-Methylquinoxaline (3db).
Gray solid. 1H NMR (300 M, CDCl3): δ 8.05 (2H, J = 8.4 Hz, d), 7.95 (1H, s), 7.62-7.57
(3H, t), 6.67-6.55 (4H, m), 2.60 (3H, s); 13C NMR (75 MHz, CDCl3): δ 150.89, 144.18,
144.04, 142.56, 141.85, 141.20, 140.68, 139.10, 132.84, 128.62, 127.94, 112.92, 112.64,
111.90, 111.87, 21.94; HRMS calcd for C17H12N2O2 (M+H)+ 277.0972; found: 277.0970.
2,3-Di(Furan-2-Yl)-6,7-Dimethylquinoxaline (3dc).
Yellow solid. 1H NMR (300 M, CDCl3): δ 7.89 (2H, s), 7.606-7.60 (2H, t), 6.61-6.54 (4H,
m), 2.50 (6H, s); 13C NMR (75 MHz, CDCl3): δ 151.08, 143.88, 141.85, 141.16, 139.64,
128.17, 112.38, 111.79, 20.41; HRMS calcd for C18H14N2O2 (M+H)+ 291.1128; found:
291.1129.
6-Chloro-2,3-Di(Furan-2-Yl)Quinoxaline (3dd).
Gray solid. 1H NMR (300 M, DMSO-d6): δ 8.19 (1H, J = 2.1 Hz, d), 8.16 (1H, J = 9.0 Hz,
d), 7.94-7.87 (3H, m), 6.78-6.72 (4H, m); 13C NMR (75 MHz, DMSO-d6): δ 150.03,
12

149.95, 145.32, 145.15, 142.83, 140.28, 138.59, 135.12, 131.37, 130.50, 127.36, 113.58,
113.28, 112.29, 112.25; HRMS calcd for C16H9ClN2O2 (M+H)+ 297.0425; found:
297.0427.
2,3-Di(Furan-2-Yl)-6-Nitroquinoxaline (3de).
Yellow solid. 1H NMR (300 M, DMSO-d6): δ 8.83 (1H, J = 2.7 Hz, d), 8.51 (1H, J = 2.4,
13
9.3 Hz, dd), 8.27 (1H, J = 9.0 Hz, d), 8.00-7.98 (2H, m), 6.93-6.76 (4H, m); C NMR (75
MHz, DMSO-d6): δ 149.74, 149.64, 147.70, 146.10, 145.66, 144.20, 143.67, 143.48,
138.58, 130.43, 124.55, 123.86, 115.10, 114.26, 112.62, 112.43; HR MS calcd for
C16H9N3O4 (M+H)+ 308.0666; found: 308.0677.
2,3-Di(Pyridin-2-Yl)Quinoxaline (3ea).
Yellow solid. 1H NMR (300 M, DMSO-d6): δ 8.29-8.20 (4H, m), 8.03-7.93 (6H, m),
7.38-7.34 (2H, m); 13C NMR (75 MHz, DMSO-d6): δ 158.09, 153.54, 149.20, 141.37,
137.94, 132.14, 130.08, 125.01, 124.39; HRMS calcd for C18H12N4 (M+H)+ 285.1135;
found: 285.1135.
6-Methyl-2,3-Di(Pyridin-2-Yl)Quinoxaline (3eb).
Yellow solid. 1H NMR (300 M, CDCl3): δ 8.39-8.37 (2H, m), 8.12 (1H, J = 8.7 Hz, d),
8.00-7.94 (3H, m), 7.85-7.78 (2H, m), 7.66 (1H, J = 8.7, 2.1 Hz, dd), 7.26-7.22 (2H, m);
13

13C NMR (75 MHz, CDCl3 ): δ 157.46, 152.18, 148.43, 141.27, 142.19, 139.69, 136.73,
132.90, 128.90, 124.32, 124.30, 122.95, 122.89, 21.95; HRMS calcd for C19H14N4
(M+H)+ 299.1291; found: 299.1294.
6-Chloro-2,3-Di(Pyridin-2-Yl)Quinoxaline (3ed).
Yellow solid. 1H NMR (300 M, DMSO-d6): δ 8.32-8.24 (4H, m), 8.03-7.93 (5H, m),
7.40-7.34 (2H, m); 13C NMR (75 MHz, DMSO-d6): δ 156.94, 156.90, 153.63, 153.04,
148.46, 140.95, 139.28, 137.22, 135.65, 131.94, 128.04, 124.29, 124.24, 123.82, 123.76;
HRMS calcd for C18H11ClN4 (M+H)+ 319.0745; found: 319.0745.
6-Nitro-2,3-Di(Pyridin-2-Yl)Quinoxaline (3ee).
1
Yellow solid. H NMR (300 M, DMSO-d6): δ 9.04 (1H, J = 2.7 Hz, d), 8.49 (1H, J = 2.4,
9.0 Hz, dd), 8.25 (1H, J = 9.0 Hz, d), 7.49-7.45 (4H, m), 7.26-7.17 (4H, t); 13C NMR (75
MHz, DMSO-d6): δ 156.08, 154.93, 154.34, 148.18, 148.10, 142.75, 139.10, 137.01,
130.89, 124.95, 124.19, 124.08, 123.96, 123.81, 123.71; HRMS calcd for C18H11N5O2
(M+H)+ 330.0986; found: 330.0981.
ACKNOWLEDGEMENTS
We are grateful to the National Science Foundation of China (No. 21572117) and State
Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of
14

Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical Col-
lege (No. GTZK201405) for financial support of this research.
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16

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17

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19

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20

Table 1. Optimization of reaction conditions for the one-pot synthesis of 3aa
Entry
1
Acid
Solvent
DME
Yieldb (%)
n.d
TsOH·H2O
TsOH·H2O
TsOH·H2O
TsOH·H2O
TsOH·H2O
TsOH·H2O
MSA
2
DCE
n.d
3
Toluene
PhCl
n.d
4
n.d
5
MeCN
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
n.d
6
90
7
91
8
TfOH
90
9
none
Trace
73
10c
11d
12e
13f
14g
TsOH·H2O
TsOH·H2O
TsOH·H2O
TsOH·H2O
TsOH·H2O
90
89
82
90
aReaction conditions: 1a (1 mmol), acid (50 mol%), solvent (2 mL), in a sealed tube at
100 oC under air atmosphere for 5h. This reaction mixture were added 2a (1 mmol), until
the disappearance of 2a, monitored by TLC. [b] Yield of isolated product. [c] TsOH (40
mol%) was used. [d] TsOH (60 mol%) was used. [e] TsOH (80 mol%) was used. [f]
21

Reaction conditions: 1a (1 mmol), 2a (1 mmol), acid (50 mol%), solvent (2 mL), in a
sealed tube at 100 oC under air atmosphere for 5h. [g] Under air.
DME: 2-methoxyethyl ether; DCE: 1,2-dichloroethane.
22

Table 2. Scope of 4-substituted benzene-1,2-diamines and 2-hydroxy-1,2-
diarylethanonesa
Entry
1
Ar
R
t1 (h)
5
Product
3aa
3ab
3ac
Yield (%)b
C6H5
H
90
93
92
85
92
89
88
87
84
85
86
85
81
78
83
85
87
2
C6H5
4-CH3
4,5-Dimethyl
4-Cl
5
3
C6H5
5
4
C6H5
5
3ad
3ae
5
C6H5
4-NO2
H
5
6
4-CH3C6H4
4-CH3C6H4
4-CH3C6H4
4-CH3C6H4
4-CH3OC6H4
4-CH3OC6H4
4-CH3OC6H4
4-CH3OC6H4
4-CH3OC6H4
Furan-2-yl
Furan-2-yl
Furan-2-yl
5
3ba
3bb
3bc
3be
3ca
3cb
3cc
7
4-CH3
4,5-Dimethyl
4-NO2
H
5
8
5
9
5
10
11
12
13
14
15
16
17
6
4-CH3
4,5-Dimethyl
4-Cl
6
6
6
3cd
3ce
4-NO2
H
6
5
3da
3db
3dc
4-CH3
4,5-Dimethyl
5
5
23

18
19
20
21
22
23
Furan-2-yl
Furan-2-yl
Pyridin-2-yl
Pyridin-2-yl
Pyridin-2-yl
Pyridin-2-yl
4-Cl
5
5
1
1
1
1
82
80
92
89
88
87
3dd
3de
3ea
3eb
3ed
3ee
4-NO2
H
4-CH3
4-Cl
4-NO2
aReaction conditions: 1,2-diaryl-2-hydroxyethanone 1 (1.0 mmol), PTSA (0.5 mmol) in
DMSO (2 mL) was heated to 100 oC (TLC monitored), then o-diaminobenzene (1
mmol)was added.
bIsolated yield
24

Scheme 1. A serendipity.
25

Scheme 2. Repeated test under N2.
26

Scheme 3. Previous work and our idea.
27

Scheme 4. Structures of the desired compounds 3aa–ee.
28

Scheme 5. Control Experiments.
29