Poly(N,N ′-dibromo-N-ethyl-benzene-1,3-disulphonamide) and N,N,N ′,N ′-tetrabromobenzene-1,3- disulphonamide as novel catalysts for synthesis of quinoxaline derivatives

Article abstract of DOI:10.1007/s12039-013-0386-x

Poly(N,N ^′ -dibromo-N-ethyl-benzene-1,3-disulphonamide) [PBBS] and N,N,N ^′,N ^′ -tetrabromobenzene-1,3- disulphonamide [TBBDA] were used as efficient catalysts for the synthesis of quinoxaline derivatives in excellent yields from 1,2-diamines and 1,2-dicarbonyls under aqueous and solvent-free conditions. [Figure not available: see fulltext.]

Full text of DOI:10.1007/s12039-013-0386-x

J. Chem. Sci. Vol. 125, No. 2, March 2013, pp. 353–358. ꢀc Indian Academy of Sciences.
ꢀ
Poly(N,N -dibromo-N-ethyl-benzene-1,3-disulphonamide)
ꢀ
ꢀ
and N,N,N ,N -tetrabromobenzene-1,3-disulphonamide
as novel catalysts for synthesis of quinoxaline derivatives
RAMIN GHORBANI-VAGHEI and SOMAYE HAJINAZARIb
a,∗
a
Department of Organic Chemistry, Faculty of Chemistry, Bu–Ali Sina University, 65174, Hamedan, Iran
Payame Noor University, 65199-9951, Hamedan, Iran
b
e-mail: rgvaghei@yahoo.com
MS received 19 January 2012; revised 16 August 2012; accepted 27 September 2012
ꢁ
ꢁ
ꢁ
Abstract. Poly(N,N -dibromo-N-ethyl-benzene-1,3-disulphonamide) [PBBS] and N,N,N ,N -tetrabromo-
benzene-1,3-disulphonamide [TBBDA] were used as efficient catalysts for the synthesis of quinoxaline deriva-
tives in excellent yields from 1,2-diamines and 1,2-dicarbonyls under aqueous and solvent-free conditions.
Keywords. Quinoxaline; 1,2-diamines; 1,2-dicarbonyls; PBBS; TBBDA.
1
. Introduction
many of these processes suffer from one or other limi-
tations such as drastic reaction conditions, low pro-
duct yields, tedious work-up procedures, the use of
toxic metal salts as catalysts, and relatively expensive
reagents.
Quinoxaline derivatives are the subject of considerable
interest from both academic and industrial perspec-
tive. Quinoxaline and their derivatives are important
in modern drug research because of their extensive bio-
logical activities.1 Quinoxalines play an important
role as a basic skeleton for the design of a number of
antibiotic, anticancer and antiviral drugs.5 In addition
–4
2. Experimental
,6
to medicinal applications, quinoxaline derivatives have 2.1 General procedure for quinoxaline synthesis
7
found applications as dyes, efficient electron lumi- using TBBDA and PBBS in the presence of solvent
8
9
nescent material, organic semiconductors and DNA
10
To a stirred suspension of 1,2-dicarbonyl compound
cleaving agents. Based on the significant applica-
tions of quinoxaline compounds in both medicinal
and industrial fields, a number of synthetic strate-
gies have been developed for the preparation of sub-
stituted quinoxalines. The most common method is
the condensation of an aryl-1,2-diamine with a 1,2-
dicarbonyl compound in refluxing ethanol or acetic
(
(
(
1 mmol) and 1,2-diamine (1 mmol) in H O:EtOH (2:1)
3 mL) was added TBBDA (0.1 g, 0.2 mmol) or PBBS
0.1 g). The resulting mixture was stirred at room tem-
2
perature for the specified time (table 1). The reaction
was monitored by TLC (5:1, n-hexane/acetone). After
completion of the reaction, CH Cl (10 mL) was added
2
2
11
and organic layer was separated and dried (MgSO ).
acid. Improved methods have been reported for the
synthesis of quinoxaline derivatives including the bi-
4
Evaporation of the solvent under reduced pressure gave
the crude product. Recrystallization from 96% ethanol
to afford the pure product.
12
catalysed oxidative coupling, a solid-phase synthe-
1
3
14,15
16
17
sis, microwave,
and the use of MnO2, POCl3,
18
19
20
zeolites,
iodine,
cerium ammonium nitrate,
21
22
23
Ga(OTf)3, CuSO .5H O, SA/Me, polyaniline- 2.2 General procedure for quinoxaline synthesis
4
2
2
4
25
sulphate salt,
silica bonded s-sulphonic acid,
using TBBDA and PBBS under solvent-free conditions
26
27
montmorillonite K-10, polyethylene glycol, ZrO2/
Ga O /MCM-41 as catalyst or promoter. However,
2
8
1
,2-Dicarbonyl compound (1 mmol), 1,2-diamine
2
3
(1 mmol), and TBBDA (0.1 g, 0.2 mmol) or PBBS
(
0.1 g) was placed in a test-tube. The mixture was
◦
stirred at 80 C. After completion of the reaction
∗
For correspondence
[table 1, monitored by TLC (5:1, n-hexane/acetone)],
353

354
Ramin Ghorbani-Vaghei and Somaye Hajinazari
Table 1. Synthesis of different quinoxalines using symmetrical aromatic 1,2-diketone.
TBBDA
solvent-free)
PBBS
(solvent-free)
TBBDA
(H2O:EtOH)
PBBS
(H2O:EtOH)
(
Yield/time
(%/min)
Yield/time
(%/min)
Yield/time
(%/min)
Yield/time
(%/min)
Entry
1
Producta
N
N
98/3
95/5
90/15
90/20
95/10
95/10
85/30
90/35
N
N
Me
2
3
N
Br
90/25
85/60
80/70
75/120
N
N
O
N
N
4
5
6
90/25
95/5
94/8
85/45
90/15
90/25
85/120
95/10
95/10
80/180
95/20
87/30
N
N
N
N
H
3
CO
N
7
8
9
95/5
92/8
90/15
85/20
80/50
95/15
90/15
90/35
80/35
N
H
3
CO
H CO
3
N
CH
3
N
H CO
3
H
H
3
CO
O
N
N
90/20
70/120
75/180
3
CO

Easy synthesis of quinoxalines
355
Table 1. (continued).
TBBDA
solvent-free)
PBBS
(solvent-free)
TBBDA
(H2O:EtOH)
PBBS
(H2O:EtOH)
(
Yield/time
(%/min)
Yield/time
(%/min)
Yield/time
(%/min)
Yield/time
(%/min)
Entry
Producta
3
H CO
N
N
1
0
1
95/5
90/10
90/20
80/30
85/30
80/55
75/65
H
3
CO
H
3
CO
N
N
1
96/10
H CO
3
N
N
1
2
3
95/5
97/8
90/15
90/20
90/10
85/15
85/25
85/25
N
N
Me
1
O
N
N
14
90/35
75/90
85/120
70/250
N
1
5
6
95/8
97/5
90/25
94/20
90/10
90/15
85/40
80/25
N
N
Me
1
N
N
N
N
Ph
Ph
1
7
8
85/20
95/15
85/45
87/60
95/30
90/40
90/70
80/60
N
N
N
Ph
Ph
N
H3C
CH3
1
N
H C
CH3
3
aProducts were characterized from their physical properties, by comparison with authentic samples, and by spectroscopic
methods.
CH Cl (10 mL) was added, and catalyst was removed solvent under reduced pressure gave the crude product.
2
2
by filteration. The organic phase was washed with Recrystallization from 96% ethanol to afford the pure
H O (10 mL) and dried (MgSO ). Evaporation of the product.
2
4

356
Ramin Ghorbani-Vaghei and Somaye Hajinazari
R2
R2
R1
R1
O
O
H N
R1
R1
N
N
2
TBBDA or PBBS
+
o
Solvent-free, 80 C
or
H N
X
X
2
H O: E: tOH (2:1), r.t.
2
R =alkyl, aryl
1
R = alkyl, aryl, Br
2
X =C, N
Br
N
Br
N
Br
N
Br
N Br
Br
CH2
CH2
S
S
S
S
O
O
O
O
n
O
O
O
O
TBBDA
PBBS
Scheme 1. Synthesis of quinoxaline derivatives.
−
1 1
2
.2a Analytical data for C H BrN (entry 3): 1597, 722 cm . H NMR (FT-400 MHz, CDCl ): δ =
19
12
3
3
◦
13
Solid; mp 157–158 C. IR (KBr): 3062, 1658, 1593, 8.36 (s, 2H), 8.1 (s, 4H), 2.7 (s, 12H); C NMR
−1 1
1
450 cm . H NMR (FT-90 MHz, CDCl ) δ = 9.1 (d, (FT-400 MHz, CDCl ) δ = 154.33, 142.50, 141.07,
3
3
J 2.6 Hz, 1H), 8.6 (d, J 2.4 Hz, 1H), 7.25–7.7 (m, 10H); 142.92, 140.51, 139.4, 138.04, 130.15, 130.47, 20.78;
13
c NMR (FT-90 MHz, CDCl ) δ = 156.17, 155.14, m/z = 314.
3
154.8, 139.4, 137,77, 137.45, 129.50, 129.30, 129.26,
128.12, 124.9; m/z = 362.
3
. Results and discussion
2
.2b Analytical data for C H N O (entry10): In continuation of our interest in the application of po-
18
18
2
2
◦
ꢁ
Solid; mp 113–115 C. IR (KBr): 3057, 2939, 2841, ly(N,N -dibromo-N-ethyl-benzene-1,3-disulphonamide)
1
−1 1
ꢁ
ꢁ
2
664, 1602, 1556,1440, 850 cm . H NMR (FT- [PBBS], N,N,N ,N -tetrabromobenzene-1,3-disulpho-
9
30–40
9
0 MHz, CDCl ) δ = 7.29 (d, J 8.7 Hz, 4H), 6.79 (d, namide [TBDDA], in organic synthesis,
we
3
13
J 9 Hz, 4H), 3.76 (s, 6H), 3.61 (s, 4H); C NMR (FT- report here a convenient method for the preparation
5
00 MHz, CDCl ) δ = 161.06, 159.92, 130.91, 129.93, of quinoxaline derivatives from various 1,2-diamines
3
113.83, 55.62, 46.07; m/z = 294.
with 1,2-dicarbonyls in the presence of TBBDA and
PBBS under (i) aqueous and (ii) solvent-free conditions
(
scheme 1).
2
.2c Analytical data for C H N O (entry11):
22
24
2
2
Under solvent-free conditions, most of the reactions
◦
Solid; mp 173–175 C. IR (KBr): 2933–3079, 2933,
proceeded to afford the corresponding product in less
time. In another study, the effect of different solvents
upon the reaction was investigated (table 2). The results
showed that the examined solvents were not suitable
separately. The satisfactory results were obtained when
−1 1
2831, 1608, 1456–1596, 1336, 800 cm . H NMR (FT-
9
0 MHz, CDCl ): δ = 7.33 (d, J 7.8 Hz, 4H), 6.79
3
(d, J 8.5 Hz, 4H), 3.73 (s, 6H), 2.8 (m, 2H), 2.4 (m,
13
2
H), 1.3–1.9 (m, 6H); C NMR (FT-500 MHz, CDCl )
3
δ = 161.06, 159.40, 130.57, 113.92, 59.71, 55.68,
a mixture H O and EtOH was used as solvent. The
best ratio of H O/EtOH (v/v) was found to be 2/1.
2
33.97, 25.8; m/z = 348.
2
2
.2d Analytical data for C H N O (entry14):
27
16
2
◦
Table 2. Screening for optimum reaction conditions.
Solid; mp 210–213 C. IR (KBr): 3060, 29 26, 1723,
−1
1
1
9
7
654, 1602–1404, 1258, 756 cm . H NMR (FT-
Entry
Conditions
Time (min)
Yield (%)
0 MHz, CDCl ): δ = 9.32 (m, 2H), 8.39–8.8 (m, 4H),
3
.4–7.94 (m, 10H; 13C NMR (FT-90 MHz, CDCl )
1
2
3
4
5
6
7
8
EtOH
CHCl3
H2O
CH3CN
CH2Cl2
H2O/EtOH (2:1)
Solvent-free (80 C)
Solvent-free (r.t)
45
100
40
70
120
10
90
65
85
97
70
95
98
–
3
δ = 181.33, 146.40, 143.57, 142.92, 140.21, 138.4,
36.04, 134.5, 130.47, 129.62, 128.47, 126.2, 124.03;
m/z = 384.
1
◦
3
240
2.2e Analytical data for C H N (entry18): Solid;
20 18 4
◦
mp 238–240 C. IR (KBr): 3050, 2925, 2848, 1656,

Easy synthesis of quinoxalines
357
N
N
Ph
Ph
Ph
Ph
O
O
N
N
Ph
Ph
or
TBBDA or PBBS
H N
NH2
NH2
+
2
or
o
Solvent-free, 80 C
or
H
2
N
:
H
3
C
O
H
2
O:EtOH (2:1), r.t.
N
N
H
3
C
CH
3
H
3
C
O
N
N
H
3
C
CH
3
Scheme 2. Synthesis of biquinoxalinyl.
ꢁ
Table 3. The recycling of TBBDA in the synthesis of
quinoxaline.
Poly(N, N -dibromo-N-ethyl-benzene-1, 3-disul-
ꢁ
ꢁ
phonamide) [PBBS], N, N, N , N -tetrabromobenzene-
,3-disulphonamide [TBDDA] are inexpensive and
1
Entry
Time (min)
Yield (%)
non-hazardous catalyst. They react under heteroge-
neous conditions, are conveniently handled, and can be
removed from the reaction mixture by simple filtration.
We also found that TBBDA and PBBS were reusable
catalyst runs, the catalytic activities of the reagent were
almost the same as those of fresh catalysts.
1
2
3
4
3
3
3
3
98
95
92
88
In conclusion, we have described an efficient method
So we chose this solvent system for environmental for the synthesis of quinoxaline derivatives utilizing
acceptability.
TBBDA and PBBS. This method provides an excellent
Substituted quinolines were prepared from various complement quinoxaline derivatives synthesis and also
,2-diamines with 1,2-dicarbonyls compounds. The avoids the use of hazardous acids or bases.
1
results are presented in table 1. In the absence of
TBBDA or PBBS, the reaction did not proceed even for by the condensation of 3,3 ,4,4 -tetramino-1,1 -biphenyl
period of 10 h.
with two equivalents of 1,2-dicarbonyl compounds
Also, we have synthesized biquinoxalinyl (scheme 2)
ꢁ
ꢁ
ꢁ
N
Ph
Ph
Ph
Ph
O
O
Br
N
Br
N
Br
Br
N
S
S
O
O
O
O
Br
O
O
Ph
Ph
TBBDA-
N
Ph
N
H
Ph
TBBDA-
O
H
2
N
Br
H
2
N
Br
N
Ph
Ph
H
O
N
Ph
NH
2
O
Ph
TBBDA-
NH
2
O
TBBDA-
Br
N
Ph
Ph
NH
2
O
TBBDA
TBBDA
+
2
H O
Scheme 3. Possible mechanism for the synthesis of quinoxaline derivatives.

358
Ramin Ghorbani-Vaghei and Somaye Hajinazari
◦
under (i) solvent-free at 80 C, and (ii) solvent condi- 10. Gobec S and Urleb U 2004 In Science of synthesis,
Houben Weyl methods of molecular transformations cat-
egory 2, 16, (ed.) Y Yamamoto (Stuttgart-New York:
Georg Thieme Verlag) p. 845
tions (H O:EtOH at room temperature).
Our experiments also determined that TBBDA is a
reusable catalyst and after four runs its catalytic activity
is almost the same as that of a fresh catalyst. The sum-
mary of this part of the experiment is shown in table 3.
2
1
1. Brown D J 2004 In The chemistry of heterocyclic com-
pounds (eds) E C Taylor and P Wipf (New Jersey: John
Wiley & Sons)
The first run, in the presence of TBBDA and under 12. Antoniotti S and Donach E 2002 Tetrahedron Lett. 43
3
971
solvent-free conditions, gave 98% yield of quinoxaline.
The second run, with TBBDA recovered from the first
run, gave 95% of the products. The average chemical
yield for four consecutive runs was 93%. The result of
all four runs are shown in table 3.
1
1
3. Wu Z and Ede N J 2001 Tetrahedron Lett. 42 8115
4. Zhao Z, Wisnoski D D, Wolkenberg S E, Leister W H,
Wang Y and Lindsley C W 2004 Tetrahedron Lett. 45
4873
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Since TBBDA contains bromine atoms which are
bonded to nitrogen atoms, it is possible that this cata-
1
1
1
+
lyst releases Br in situ, which can act as an elec-
30–40
trophilic species.
Therefore, the following mecha-
nism can be suggested for the synthesis of quinoxaline
derivatives (scheme 3).
8. Bhosale R S, Sarda S R, Ardhapure S S, Jadhav W N,
Bhusare S R and Pawar R P 2005 Tetrahedron Lett. 46
7183
1
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4
. Conclusion
2
2
0. More S V, Sastry M N V and Yao C F Green Chem. 8 91
1. Cai J J, Zou J P and Zhang W 2008 Tetrahedron Lett.
In conclusion, we have described an efficient method
for the synthesis of quinoxaline derivatives utilizing
TBBDA and PBBS. This method provides an excellent
complement quinoxaline derivatives synthesis and also
avoids the use of hazardous acids or bases.
4
9 7386
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2
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We thank Bu-Ali Sina University, Center of Excellence
and Development of Chemical Methods (CEDCM) for
financial support.
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1