Catalytic application of N,2-dibromo-6-chloro-3,4-dihydro-2H-benzo[e][1,2,4]thiadiazine-7-sulfonamide 1,1-dioxide as a new catalyst for the synthesis of 9-aryl-1,8-dioxo-octahydroxanthenes under neutral media

Article abstract of DOI:10.1007/s11164-016-2492-0

Abstract: A new N-bromo sulfonamide reagent, namely N,2-dibromo-6-chloro-3,4-dihydro-2H-benzo[e][1,2,4]thiadiazine-7-sulfonamide 1,1-dioxide, was synthesized and used as a new and highly efficient catalyst for the preparation of 9-aryl-1,8-dioxo-octahydro

Full text of DOI:10.1007/s11164-016-2492-0

Res Chem Intermed
DOI 10.1007/s11164-016-2492-0
Catalytic application of N,2-dibromo-6-chloro-3,4-
dihydro-2H-benzo[e][1,2,4]thiadiazine-7-sulfonamide
1,1-dioxide as a new catalyst for the synthesis of 9-aryl-
1,8-dioxo-octahydroxanthenes under neutral media
Ardeshir Khazaei1 Fatemeh Abbasi1
•
•
Ahmad Reza Moosavi-Zare2
Received: 10 October 2015 / Accepted: 21 February 2016
Ó Springer Science+Business Media Dordrecht 2016
Abstract A new N-bromo sulfonamide reagent, namely N,2-dibromo-6-chloro-3,4-
dihydro-2H-benzo[e][1,2,4]thiadiazine-7-sulfonamide 1,1-dioxide, was synthesized and
used as a new and highly efficient catalyst for the preparation of 9-aryl-1,8-dioxo-
octahydroxanthene derivatives by the condensation reaction of dimedone (5,5-
dimethylcyclohexane-1,3-dione) and various arylaldehydes. Mechanistically, it is
interesting that in situ generation of the Br? ion from the catalyst is successfully cat-
alyzed by this reaction under neutral media.
Graphical Abstract
DCDBTSD (10 mol%)
O
H
N
O
O
O
N
Br
S
S
Br
Ar
O
H
O
O
Ar
O
O
O
O
Cl
N
H
Solvent-free / 90 °C
O
Electronic supplementary material The online version of this article (doi:10.1007/s11164-016-2492-0)
contains supplementary material, which is available to authorized users.
&
&
Ardeshir Khazaei
Khazaei_1326@yahoo.com
Ahmad Reza Moosavi-Zare
moosavizare@yahoo.com
1
2
Faculty of Chemistry, Bu-Ali Sina University, Hamedan 6517838683, Islamic Republic of Iran
Department of Chemistry, Sayyed Jamaleddin Asadabadi University, Asadabad 6541835583,
Islamic Republic of Iran
123

A. Khazaei et al.
Keywords N–halo reagent Á Dimedone (5,5-dimethylcyclohexane-1,3-dione) Á
Aldehyde Á 9-aryl-1,8-dioxo-octahydroxanthene Á Solvent-free
Introduction
Solvent-free reactions have been demonstrated to be an efficient technique for
various organic transformations instead of using harmful organic solvents. Solvent-
free conditions often lead to a remarkable decrease in reaction times, increased
yields, easier workup, matching with green chemistry protocols, and may enhance
the regioselectivity and stereoselectivity of reactions [1–4].
Heterocycles are extensively applied in organic synthesis, pharmaceutical
chemistry and industry. For example, xanthene derivatives have various significant
biological activities. They are used as antibacterial, anti-inflammatory [5], and
antiviral agents [6] and offer potential applications in photodynamic therapy [7].
Moreover, xanthenes are used as a bactericide [8], as dyes in fluorescent materials
for visualization of bio-molecules [9], and in laser technology [10]. Some synthetic
procedures, wherein suitable active methylene carbonyl compounds are condensed
with aldehydes, are available for the synthesis of xanthenes derivatives. Moreover,
several synthetic routes have been developed for the preparation of 9-aryl-1,8-
dioxo-octahydroxanthenes via the condensation of dimedone (5,5-dimethylcyclo-
hexane-1,3-dione) with aldehydes using various catalysts, such as nano-TiO2 [11],
P2O5/SiO2 [12], ZrOCl2Á8H2O [13], TCCA [14], silica sulfuric acid [15], Fe3?
-
montmorillonite [16], DBH [17], TMSCl [18], Fe(HSO4)3 [19], [Msim]Cl [20],
[Et3N–SO3H]Cl [21], and PEG-SO3H [22]. Nevertheless, because of the importance
of 9-aryl-1,8-dioxo-octahydroxanthenes, introducing a highly efficient and eco-
friendly catalyst with high novelty is still needed.
Some specific features of N-halo reagents, including the high activity of the N–
X bond and the various modes of splitting of this bond, have led to their wide
application in organic synthesis [23]. Due to the considerable characteristics of N-
halo reagents and the use in applications of these compounds [24–27], a novel and
effective N-halo reagent, namely N,2-dibromo-6-chloro-3,4-dihydro-2H-ben-
zo[e][1,2,4] thiadiazine-7-sulfonamide 1,1-dioxide (DCDBTSD), was synthesized
[28] (Scheme 1) and tested on the synthesis of 9-aryl-1,8-dioxo-octahydroxanthenes
(Scheme 2).
O
Scheme 1 The structure of N,2-
dibromo-6-chloro-3,4-dihydro-
2H-benzo[e][1,2,4] thiadiazine-
7-sulfonamide 1,1-dioxide
(DCDBTSD)
H
N
O
O
N
Br
S
S
Br
O
Cl
N
H
123

Catalytic application of N,2-dibromo-6-chloro-3,4-dihydro-…
O
O
Ar
O
O
O
DCDBTSD (10 mol%)
2
+
O
Ar
H
Solvent-free/90 °C
Scheme 2 The synthesis of 9-aryl-1,8-dioxo-octahydroxanthenes
Experimental
General
Chemicals were purchased from Merck and Aldrich and used without further
purification. All yields refer to isolated products after purification. The reactions
were monitored by thin-layer chromatography (TLC) carried out on silica plates.
The products were characterized by comparison of their physical data with those of
known samples or by their spectral data. Infrared (IR) spectra were recorded on a
1
Shimadzu IR 470 spectrophotometer. The H NMR (500, 400 or 90 MHz) and 13C
NMR (100 MHz) were run on a Bruker-NMR spectrometer (d in ppm) using TMS
as an internal standard in chloroform (CDCl3) and dimthylsulfoxide (DMSO) as the
solvents. Mass spectra were recorded on an Agilent technologies (HP) 5973 network
mass selective detector (MSD) operating at an ionization potential of 70 eV.
Melting points were determined in open capillaries with a Stuart Scientific melting
point apparatus. TLC was performed on silica–gel polygram SILG/UV 254 plates.
Thermal gravimetry (TG) and differential thermal gravimetric (DTG) were analyzed
by a Perkin Elmer Pyris 1. TG/DTG analysis was at 30–618 °C,with a temperature
increase rate of 10 °C min-1, and in nitrogen atmosphere. Melting points were
recorded on a Stuart Scientific melting point apparatus in open capillary tubes. The
crystal structure of the synthesized materials was determined using an X-ray
diffractometer (XRD; Ital structure ADP 2000) at ambient temperature.
General procedure for the synthesis of DCDBTSD (Scheme 1)
A solution of sodium hydroxide (6 mol L-1, 1 mL) was added dropwise to a stirring
round-bottomed flask (50 mL) containing hydrochlorothiazide (0.60 g, 2 mmol) in
distilled water (2 mL) during 10 min at room temperature. After the addition was
completed, the reaction mixture was stirred for 20 min. Then, bromine (0.16 mL,
3 mmol) was slowly added to the stirring solution of hydrochlorothiazide during
15 min at 0 °C. The insoluble brominated catalyst was removed by filtration and
washed with H2O (10 mL) to giveDCDBTSD in 90 % yield (0.82 g) [25].
Spectral data of DCDBTSD
White solid; Yield: 90 %; mp 255 °C (mp 255 °C [25]); IR (KBr): 3377, 3232,
1579, 1495, 1362, 1308, 1244, 1147, 1058, 1025 cm-1 1H NMR (400 MHz,
;
DMSO-d6): d (ppm) 4.70 (s, 2H), 6.85 (s, 1H), 7.20 (s, 1H), 7.88 (s, 1H), 8.07 (s,
123

A. Khazaei et al.
1H);13C NMR (100 MHz, DMSO-d6): d (ppm) 55.08, 107.26, 110.65, 122.57,
127.55, 136.34, 142.14; MS m/z observed: 455 (M?), 438, 424.
General procedure for the synthesis of 9-aryl-1,8-dioxo-octahydroxanthene
using DCDBTSD (Scheme 2) (compound 1–21)
A mixture of dimedone (2 mmol), aromatic aldehyde (1 mmol) and DCDBTSD
(0.0455 g, 10 mol %) in a 10-mL round-bottomed flask connected to a reflux
condenser was stirred in an oil bath (90 °C) for the appropriate time (Table 2). After
completion of the reaction, as monitored by TLC, the reaction mixture was cooled
to room temperature and recrystallized from ethanol (95 %). The pure products
1
(compounds 1–21) were identified by IR, H, 13CNMR and MS spectra.
Spectral data of the products
3,3,6,6-tetramethyl-9-phenyl-3,4,5,6,7,9-hexahydro-1H-xanthene-1,8(2H)-dione (1)
White solid; Yield: 85 %; mp 203–205 °C (lit. [14] mp 203–205 °C); IR (KBr) m/
cm-1 3062, 3032, 2957, 2915, 2871, 1678, 1662, 1625, 1467, 1454, 1362, 1199,
1140, 1002, 699, 555; 1H NMR (500 MHz, DMSO-d6) d 0.90 (s, 6H), 1.04 (s, 6H),
2.09 (d, J = 16.1 Hz, 2H), 2.27 (d, J = 16.2 Hz, 2H), 2.53 (d, J = 17.1 Hz, 2H),
2.58 (d, J = 17.7 Hz, 2H), 4.53 (s, 1H), 7.10 (t, J = 7.0 Hz, 1H), 7.18 (d,
J = 7.0 Hz, 2H), 7.21 (t, J = 7.20 Hz, 2H).
3,3,6,6-tetramethyl-9-(2-nitrophenyl)-3,4,5,6,7,9-hexahydro-1H-xanthene-1,8(2H)-
dione (2)
White solid; Yield: 82 %; mp 256–257 °C (lit. [14] mp 203–205 °C); IR (KBr) m/
cm-1 3099, 3062, 2960, 2932, 2872, 1680, 1666, 1625, 1607, 1527, 1205, 796, 576;
1H NMR (90 MHz, CDCl3) d 0.99 (s, 6H, CH3), 1.08 (s, 6H, CH3), 2.18 (s, 4H),
2.47 (s, 4H), 5.52 (s, 1H), 7.35–7.70 (b, 4H).
3,3,6,6-tetramethyl-9-(3-nitrophenyl)-3,4,5,6,7,9-hexahydro-1H-xanthene-1,8(2H)-
dione (3)
White solid; Yield: 84 %; mp 173–174 °C (lit. [17] mp 170–171 °C); IR (KBr) m/
1
cm-1 3091, 2957, 1677, 1655, 1621, 1524, 1352, 1201, 1166, 1141, 1002, 692; H
NMR (90 MHz, CDCl3) d 0.97 (s, 6H, CH3), 1.09 (s, 6H, CH3), 2.18 (s, 4H), 2.49
(s, 4H), 4.80 (s, 1H), 7.28–8.00 (b, 4H).
3,3,6,6-tetramethyl-9-(4-nitrophenyl)-3,4,5,6,7,9-hexahydro-1H-xanthene-1,8(2H)-
dione (4)
White solid; Yield: 87 %; mp 237–238 °C (lit. [11] mp 224–226 °C); IR (KBr) m/
1
cm-1 2958, 2870, 1663, 1616, 1602, 1514, 1362, 1202, 1166, 868, 564; H NMR
123

Catalytic application of N,2-dibromo-6-chloro-3,4-dihydro-…
(90 MHz, CDCl3) d 0.99 (s, 6H, CH3), 1.12 (s, 6H, CH3), 2.21 (s, 4H), 2.50 (s, 4H),
4.82 (s, 1H), 7.47 (d, J = 7.2 Hz, 2H), 8.08 (d, J = 7.47 Hz, 2H).
9-(2-chlorophenyl)-3,3,6,6-tetramethyl-3,4,5,6,7,9-hexahydro-1H-xanthene-
1,8(2H)-dione (5)
White solid; Yield: 85 %; mp 226–228 °C (lit. [14] mp 225–227 °C); IR (KBr) m/
cm-1 2963, 1677, 1658, 1622, 1536, 1359, 1199, 1165, 1138, 1051, 1000, 838, 667;
1H NMR (90 MHz, CDCl3) d 1.02 (s, 6H, CH3), 1.08 (s, 6H, CH3), 2.17 (s, 4H),
2.44 (s, 4H), 4.98 (s, 1H), 7.09–7.37 (b, 4H).
9-(3-chlorophenyl)-3,3,6,6-tetramethyl-3,4,5,6,7,9-hexahydro-1H-xanthene-
1,8(2H)-dione (6)
White solid; Yield: 87 %; mp 192–193 °C (lit. [17] mp 185–187 °C); IR (KBr) m/
cm-1 3082, 2957, 2879, 1676, 1661, 1626, 1465, 1359, 1200, 1164, 1137, 1000,
1
876, 806, 695, 456; H NMR (90 MHz, CDCl3) d 0.98 (s, 6H, CH3), 1.08 (s, 6H,
CH3), 2.19 (s, 4H), 2.46 (s, 4H), 4.70 (s, 1H), 7.10–7.20 (b, 4H).
9-(4-chlorophenyl)-3,3,6,6-tetramethyl-3,4,5,6,7,9-hexahydro-1H-xanthene-
1,8(2H)-dione (7)
White solid; Yield: 91 %; mp 238–240 °C (lit. [14] mp 233–235 °C); IR (KBr) m/
cm-1 2952, 2875, 1678, 1661, 1625, 1489, 1469, 1361, 1198, 1165, 1140, 1088,
1
851, 528; H NMR (90 MHz, DMSO-d6) d 0.89 (s, 6H, CH3), 1.02 (s, 6H, CH3),
2.16 (s, 4H), 2.52 (s, 4H), 4.49 (s, 1H), 7.10–7.25 (b, 4H).
9-(2,3-dichlorophenyl)-3,4,6,7-tetrahydro-3,3,6,6-tetramethyl-2H-xanthene-1,8(5H,
9H)-dione (8)
White solid; Yield: 90 %; mp 226–227 °C; IR (KBr) m/cm-1 2956, 2868, 1683,
1670, 1625, 1356, 1196, 1003, 810, 571; 1H NMR (400 MHz, CDCl3) d 0.98 (s, 6H,
CH3), 1.07 (s, 6H, CH3), 2.18 (s, 4H), 2.45 (s, 4H), 5.03 (s, 1H), 7.09 (1H), 7.24
(1H), 7.26 (1H); 13C NMR (100 MHz, CDCl3) d 28.60, 30.35, 33.19, 33.80, 41.91,
51.82, 77.98, 78.30, 78.61, 114.68, 127.70, 129.82, 132.18, 133.08, 134.58, 143.62,
164.91, 198.18; MS m/z observed: 418 (M?), 383, 273.
9-(2,4-dichlorophenyl)-3,3,6,6-tetramethyl-3,4,5,6,7,9-hexahydro-1H-xanthene-1,8
(2H)-dione (9)
White solid; Yield: 93 %; mp 251–252 °C (lit. [18] mp 254–255 °C); IR (KBr) m/
cm-1 3071, 2962, 2932, 2877, 1680, 1660, 1623, 1585, 1473, 1358, 1198, 116, 567,
1
473; H NMR (90 MHz, CDCl3) d 1.02 (s, 6H, CH3), 1.07 (s, 6H, CH3), 2.15 (s,
4H), 2.44 (s, 4H), 5.03 (s, 1H), 6.95–7.45 (b, 3H).
123

A. Khazaei et al.
9-(4-chloro-3-nitrophenyl)-3,3,6,6-tetramethyl-3,4,5,6,7,9-hexahydro-1H-xanthene-
1,8 (2H)-dione (10)
White solid; Yield: 95 %; mp 258–260 °C; IR (KBr) m/cm-1 2963, 1658, 1622,
1
1536, 1475, 1360, 1199, 1165, 1138; H NMR (400 MHz, CDCl3) d 1.01 (s, 6H,
CH3), 1.11 (s, 6H, CH3), 2.20 (s, 4H), 2.49 (s, 4H), 4.76 (s, 1H), 7.40 (1H), 7.66
(2H); 13C NMR (100 MHz, CDCl3): d (ppm) 28.49, 30.33, 32.92, 33.39, 41.88,
51.71, 77.93, 78.25, 78.57, 115.27, 126.04, 126.18, 132.45, 135.27, 146.00, 148.69,
164.25, 198.18; IR (KBr, cm-1): 2963, 1658, 1622, 1536, 1475, 1360, 1199, 1165,
138, 999, 825, 668, 572; MS m/z observed: 429 (M?), 412, 382, 273.
9-(2-fluorophenyl)-3,4,6,7-tetrahydro-3,3,6,6-tetramethyl-2H-xanthene-1,8 (5H,
9H)-dione (11)
White solid; Yield: 85 %; mp 210–212 °C; IR (KBr) m/cm-1 2959, 2871, 1683,
1
1163, 1624, 1357, 1205, 1007, 792, 757, 573, 483; H NMR (400 MHz, CDCl3) d
0.97 (s, 6H, CH3), 1.07 (s, 6H, CH3), 2.19 (s, 4H), 2.44 (s, 4H), 4.82 (s, 1H), 6.92
(1H), 7.02 (1H), 7.44 (1H), 7.45 (1H); 13C NMR (100 MHz, CDCl3): d (ppm) 28.12,
29.35, 30.50, 33.26, 41.90, 51.82, 78.01, 78.33, 78.65, 114.69, 116.48, 116.70,
124.82, 129.30, 129.39, 131.15, 131.26, 133.15, 133.19, 161.22, 164.39, 198.01; IR
(KBr, cm-1): 2959, 2871, 1683, 1663, 1163, 1624, 1357, 1205, 1007; MS m/z
observed: 368 (M?), 311, 273.
9-(3-fluorophenyl)-3,3,6,6-tetramethyl-3,4,5,6,7,9-hexahydro-1H-xanthene-1,8
(2H)-dione (12)
White solid; Yield: 90 %; mp 231–232 °C; IR (KBr) m/cm-1 2956, 1682, 1661,
1629, 1508, 1362, 1198, 1165, 851; 1H NMR (90 MHz, CDCl3) d 0.98 (s, 6H, CH3),
1.09 (s, 6H, CH3), 2.18 (s, 4H), 2.45 (s, 4H), 4.71 (s, 1H), 6.78–7.23 (b, 4H).
9-(4-fluorophenyl)-3,3,6,6-tetramethyl-3,4,5,6,7,9-hexahydro-1H-xanthene-1,8
(2H)-dione (13)
White solid; Yield: 86 %; mp 235–236 °C; IR (KBr) m/cm-1 2958, 2928, 2875,
1682, 1661, 1627, 1508, 1362, 1199, 1141, 851.1H NMR (90 MHz, CDCl3) d 0.98
(s, 6H, CH3), 1.01 (s, 6H, CH3), 2.19 (s, 4H), 2.46 (s, 4H), 4.72 (s, 1H), 6.92 (d,
J = 7.65 Hz, 2H), 7.21 (d, J = 6.5 Hz, 2H).
9-(2-bromophenyl)-3,3,6,6-tetramethyl-3,4,5,6,7,9-hexahydro-1H-xanthene-1,8
(2H)-dione (14)
White solid; Yield: 80 %; mp 226–228 °C (lit. [12] mp 221–223 °C); IR (KBr) m/
1
cm-1 3067, 2962, 2941, 2890, 1684, 1667, 1628, 1465, 1355, 1204, 1023, 745; H
NMR (90 MHz, CDCl3) d 1.02 (s, 6H, CH3), 1.09 (s, 6H, CH3), 2.17 (s, 4H), 2.46
(s, 4H), 5.01 (s, 1H), 6.93–7.46 (b, 4H).
123

Catalytic application of N,2-dibromo-6-chloro-3,4-dihydro-…
9-(3-bromophenyl)-3,3,6,6-tetramethyl-3,4,5,6,7,9-hexahydro-1H-xanthene-1,8
(2H)-dione (15)
White solid; Yield: 83 %; mp 196–197 °C; IR (KBr) m/cm-1 3079, 2956, 2884,
1
1677, 1661, 1626, 1358, 1199, 999, 806, 695, 565; H NMR (400 MHz, CDCl3) d
1.00 (s, 6H, CH3), 1.10 (s, 6H, CH3), 2.20 (4H), 2.47 (4H), 4.70 (s, 1H), 7.09 (1H),
7.22 (1H), 7.28 (1H), 7.35 (1H).
9-(4-bromophenyl)-3,3,6,6-tetramethyl-3,4,5,6,7,9-hexahydro-1H-xanthene-1,8
(2H)-dione (16)
White solid; Yield: 84 %; mp 243–244 °C (lit. [12] mp 241–243 °C); IR (KBr) m/
cm-1 2951, 2877, 1678, 1661, 1624, 1361, 1198, 1009, 852, 526; 1H NMR
(90 MHz, CDCl3) d 0.99 (s, 6H, CH3), 1.11 (s, 6H, CH3), 2.20 (s, 4H), 2.47 (s, 4H),
4.70 (s, 1H), 7.14–7.29 (b, 4H).
3,3,6,6-tetramethyl-9-p-tolyl-3,4,5,6,7,9-hexahydro-1H-xanthene-1,8 (2H)-dione
(17)
White solid; Yield: 80 %; mp 210–211 °C (lit. [19] mp 210–213 °C); IR (KBr) m/
cm-1 2959, 2933, 2877, 1678, 1663, 1623, 1466, 1357, 1198, 999, 823, 571, 520;
1H NMR (500 MHz, CDCl3) d 1.02 (s, 6H), 1.10 (s, 6H), 2.17–2.27 (m, 7H), 2.49 (s,
4H), 4.74 (s, 1H), 7.04 (d, J = 7.5 Hz, 2H), 7.20 (d, J = 6.9 Hz, 2H).
9-(2-methoxyphenyl)-3,3,6,6-tetramethyl-3,4,5,6,7,9-hexahydro-1H-xanthene-
1,8(2H)-dione (18)
White solid; Yield: 82 %; mp 224–225 °C; IR (KBr) m/cm-1 2957, 2874, 1680,
1661, 1622, 1359, 1198; 1H NMR (400 MHz, CDCl3) d 0.95 (s, 6H, CH3), 1.08
(s, 6H, CH3), 2.16 (m, 4H), 2.41 (m, 4H), 3.77 (3H, OCH3), 4.85 (s, 1H), 6.75
(d, J = 7.2 Hz, 1H), 6.87 (d, J = 6.8 Hz, 1H), 7.11 (d, J = 8 Hz, 1H), 7.41 (d,
J = 7.5 Hz, 1H); 13C NMR (100 MHz, CDCl3): d (ppm) 27.85, 30.68, 30.72,
33.25, 42.06, 51.93, 56.27, 78.03, 78.35, 78.67, 111.77, 114.77, 121.44,
128.89, 131.62, 133.25, 158.74, 164.25, 198.21; MS m/z observed: 380 (M?),
349, 273.
9-(4-methoxyphenyl)-3,3,6,6-tetramethyl-3,4,5,6,7,9-hexahydro-1H-xanthene-1,8
(2H)-dione (19)
White solid; Yield: 94 %; mp 252–255 °C (lit. [19] mp 257–258 °C); IR (KBr) m/
cm-1 3059, 3004, 2927, 2872, 1665, 1626, 1608, 1358, 1193, 1260, 1030, 841, 569,
1
529; H NMR (90 MHz, CDCl3) d 0.98 (s, 6H, CH3), 1.08 (s, 6H, CH3), 2.18 (s,
4H), 2.44 (s, 4H), 3.71 (s, 3H, CH3), 4.68 (s, 1H), 6.88 (d, J = 7.2 Hz, 2H), 7.19 (d,
J = 7.92 Hz, 2H).
123

A. Khazaei et al.
3,3,6,6-tetramethyl-9-(3,4,5-trimethoxyphenyl)-3,4,5,6,7,9-hexahydro-1H-xanthene-
1,8 (2H)-dione (20)
White solid; Yield: 86 %; mp 212–214 °C; IR (KBr) m/cm-1 2955, 2932, 1667, 1625,
1592, 1460, 1358, 1128, 840, 571; 1H NMR (500 MHz, DMSO-d6) d 0.95 (s, 6H), 1.04
(s, 6H), 2.14 (d, J = 16.2 Hz, 2H), 2.29 (d, J = 16.2 Hz, 2H), 2.50–2.54 (Distorted AB
system, 4H), 3.31 (s, 3H), 3.60 (s, 3H), 3.69 (s, 3H), 4.50 (s, 1H), 6.42 (s, 2H).
9-(4-hydroxy-3-methoxyphenyl)-3,3,6,6-tetramethyl-3,4,5,6,7,9-hexahydro-1H-
xanthene-1,8 (2H)-dione (21)
White solid; Yield: 83 %; mp 237–239 °C (lit. [19] mp 225–227 °C); IR (KBr) m/
1
cm-1 3206, 2950, 1641, 1582, 1483, 1374, 1312, 1229, 1095, 1007, 757, 580; H
NMR (90 MHz, DMSO-d6) d 1.02 (s, 6H, CH3), 1.07 (s, 6H, CH3), 2.15 (s, 4H),
2.44 (s, 4H), 3.88 (s, 3H, OCH3), 4.71 (s, 1H), 5.31 (s, 1H, OH), 6.73–7.26 (b, 3H).
Results and discussion
The structure of DCDBTSD was identified by IR, 1H and13C NMR, XRD and mass
spectra. As can be seen in representivr IR spectrum of the catalyst and
hydrochlorothiazide in Fig. 1, two sharp peaks of N–H groups of hydrochloroth-
iazide at 3363 and 3169 cm-1 were eliminated in DCDBTSD. These differences
were proved that the two hydrogens of N–H groups in hydrochlorothiazide were
replaced with two N–Br groups in DCDBTSD.
Thermal gravimetric (TG) and derivative thermal gravimetric (DTG) analysis of
DCDBTSD was studied at range of 30–618 °C (Fig. 2).
Fig. 1 IR spectra of a DCDBTSD and b hydrochlorothiazide
123

Catalytic application of N,2-dibromo-6-chloro-3,4-dihydro-…
Fig. 2 TG/DTG diagrams of the DCDBTSD
Multi-stage decomposition pattern was observed In TG pattern and therefore
DCDBTSD could be applied as a catalyst below 200 °C and decomposed above 255 °C.
XRD pattern of DCDBTSD was studied in a domain of 5–90° (Fig. 3) and
diffraction lines of a high crystalline nature at 2h & 9.20°, 18.50°, 20.80°, 27.90°,
29.50°, 33.70°, 38.80°, 47.50° and 58.70°, and several small lines in the 25–60°
range were obtained.
After full characterization of DCDBTSD, its catalytic activity for the preparation
of 9-aryl-1,8-dioxo-octahydroxanthene was evaluated.
First, to optimize the reaction conditions (amount of catalysts and temperature) as
a model reaction, the condensation of dimedone (2 mmol) and benzaldehyde
(1 mmol) was tested in the presence of different amounts of the DCDBTSD, in the
range of 70–100 °C under solvent-free conditions (Table 1).
350
300
250
200
150
100
50
Fig. 3 XRD patterns of
DCDBTSD in comparison with
hydrochlorothiazide
Hydrochlorothiazide
Catalyst
0
0
20
40
60
80
2θ / degree
123

A. Khazaei et al.
Table 1 Optimization of the reaction conditions for synthesis of 9-aryl-1,8-dioxo-octahydroxanthene
Entry
Catalyst
Catalyst (mol%)
Temperature (°C)
Time (min)
Yielda (%)
1
2
3
4
5
6
7
8
a
No catalyst
–
90
90
180
180
45
–
Hydrochlorothiazide
DCDBTSD
DCDBTSD
DCDBTSD
DCDBTSD
DCDBTSD
DCDBTSD
10
5
–
90
77
85
85
70
74
80
10
15
10
10
10
90
30
90
30
70
45
80
40
100
30
Isolated yield
Based on Table 1, the higher yield and shorter reaction time were earned using
10 mol% of catalyst at 90 °C under solvent-free conditions. No improvement in the
reaction results was seen by increasing the quantities of the catalyst or the
temperature. The solvent-free condensation was also tested at 90 °C without
catalyst and with hydrochlorothiazide in which the reaction was not progressed even
after a long reaction time (3 h).
Table 2 The synthesis of 9-aryl-1,8-doxo-octahydro-xanthene derivatives using DCDBTSD at 90 °C
Entry
R
Time/yielda (min/%)
MP (°C) (References)
1
C6H5
30/85
40/82
40/84
30/87
25/85
20/87
20/91
25/90
25/93
15/95
40/85
35/90
30/86
40/80
40/83
35/84
20/80
35/82
30/94
25/86
35/83
203–205 (203–205) [14]
256–257 (251–253) [14]
173–174 (170–171) [17]
237–238 (224–226) [11]
226–228 (225–227) [14]
192–193 (185–187) [17]
238–240 (233–235) [14]
226–227
2
2-NO2C6H4
3-NO2C6H4
4-NO2C6H4
2-ClC6H4
3
4
5
6
3-ClC6H4
7
4-ClC6H4
8
2,3-diClC6H3
2,4-diClC6H3
4-Cl–3-NO2C6H3
2-FC6H4
9
251–252 (254–255) [18]
258–260
10
11
12
13
14
15
16
17
18
19
20
21
a
210–212
3-FC6H4
231–232 (–)
4-FC6H4
235–236 (–)
2-BrC6H4
226–228 (221–223) [12]
196–197 (–)
3-BrC6H4
4-BrC6H4
243–244 (241–243) [12]
210–211 (210–213) [19]
224–225
4-CH3C6H4
2-OCH3C6H4
4-OCH3C6H4
3,4,5-OCH3C6H2
4-OH–3-OCH3C6H3
252–255 (257–258) [19]
212–214 (–)
237–239 (225–227) [19]
Isolated yield
123

Catalytic application of N,2-dibromo-6-chloro-3,4-dihydro-…
To estimate the efficiency of DCDBTSD in the synthesis of 9-aryl-1,8-dioxo-
octahydroxanthene, the reaction of dimedone with structurally varied aromatic
aldehydes in the presence of DCDBTSD as catalyst was checked in the optimized
reaction condition (Table 2), from which it can be seen that several aromatic
aldehyde including electron-releasing and electron-withdrawing substituents and
halogens on the aromatic ring of aldehydes were successfully reacted with
dimedone to prepare corresponding products in good yields and in relatively short
reaction times.
Based on the literature [14, 26, 28–30] and the suggested mechanism
(Scheme 3), the reaction is catalyzed by in situ generation of Br? from the
DCDBTSD. By the intraction of generated Br? ion with aldehyde, intermediates
H
O
Cl
S
N
H
N
H
N
O
+
R
Br
S
Br
O
O
O
H
N
Cl
R
O
H
Br
O
H
Br
R
HN
N
O
S
S
Br
O
O
I
II
O
O
H
O
H
R
R
R
O
O
O
H
O
H
O
H
Br
O
O
O
-H2O
O
OH
O
Br
III
IV
V
R
O
H
R
O
H
Cl
S
N
H
H
N
O
-H2O
N
O
O
+
Br
S
Br
Br
O
O
O
O
O
O
VI
Scheme 3 The plausible mechanism for the synthesis of 9-aryl-1,8-doxo-octahydro-xanthene using
DCDBTSD
123

A. Khazaei et al.
Fig. 4 IR spectra of benzaldehyde and the mixture of it and DCDBTSD
I and II, as activated forms of aldehyde, are prepared. These complexes are
performed as activated carbonyl compounds and then are reacted with dimedone to
obtain intermediate III, which is converted to IV by the elimination of one molecule
H2O. Hence, V reacts with secondary dimedone to produce V and then VI is formed
by ring closing via the reaction between the hydroxyl group and the activated
carbonyl. Finally, by the elimination of another molecule of H2O from VI, the
expected product is prepared and the catalyst is regenerated for the next catalytic
cycles.
To verify the formation of intermediates I and II, benzaldehyde was reacted with
the catalyst at 90 °C, and then IR and UV spectra of the carbonyl functional group
in the reaction mixture were compared with benzaldehyde as follows: IR (Nujol): m
(cm-1) of C=O benzaldehyde from 1704 to 1692 decreased in the reaction mixture
and is indicative of the decreased nature of the double bond and the formation of
activated carbonyl (Fig. 4). Also, in the IR spectrum of this complex, two sharp
peaks at 3380 and 3253 cm-1 are observed.
1.5
Fig. 5 UV spectra of
benzaldehyde, DCDBTSD and
complexes of them and Br?
(I and II) at 90 °C in
tetrahydrofuran
Benzaldehyde
Benzaldehyde & Catalyst
Catalyst
1
0.5
0
270
320
370
/nm
123

Catalytic application of N,2-dibromo-6-chloro-3,4-dihydro-…
UV spectra were studied to confirm the structure of I and II. UV studies were
performed in tetrahydrofuran as solvent. The maximum of absorption for
benzaldehyde and catalyst appeared at 282 and 333 nm, respectively. However,
k
benzaldehyde, was observed at 282 nm (Fig. 5).
max of the complexes of aldehyde with Br?, which were formed by the addition of
Conclusion
In conclusion, we have reported a clean, efficient and simple procedure for the
preparation of 9-aryl-1,8-doxo-octahydro-xanthene via the condensation of dime-
done with aromatic aldehydes using DCDBTSD as a new, effective and
homogenous organic catalyst at 90 °C under solvent-free and neutral conditions.
The efficiency, generality, high yield, cleaner reaction profile, ease of product
isolation and simplicity are some of the advantages of this work.
Acknowledgments The authors acknowledge the Bu-Ali Sina University Research Councils, Center of
Excellence in Development of Chemistry Methods (CEDCM) and National Foundation of elites (BMN)
for support of this work.
References
1. A. Khazaei, M.A. Zolfigol, A.R. Moosavi-Zare, A. Zare, M. Khojasteh, Z. Asgari, V. Khakyzadeh, A.
Khalafi-Nezhad, Catal. Commun. 20, 54 (2012)
2. M.A. Zolfigol, A. Khazaei, A.R. Moosavi-Zare, A. Zare, V. Khakyzadeh, Appl. Catal. A Gen. 400,
70 (2011)
3. G.H. Imanzadeh, A. Khalafi-Nezhad, A. Zare, A. Hasaninejad, A.R. Moosavi-Zare, A. Parhami, J.
Iran. Chem. Soc. 4, 229 (2007)
4. G.H. Imanzadeh, A. Zare, A. Khalafi-Nezhad, A. Hasaninejad, A.R. Moosavi-Zare, A. Parhami, J.
Iran. Chem. Soc. 4, 467 (2007)
5. M.A. Zolfigol, A.R. Moosavi-Zare, P. Arghavani-Hadi, A. Zare, V. Khakyzadeh, G. Darvishi, RSC
Adv. 2, 3618 (2012)
6. R.W. Lambert, J.A. Martin, J.H. Merrett, K.E.B. Parkes, G.J. Thomas, Int Appl WO 9706178, 1997,
79. Chem. Abstr. 126, 212377y (1997)
7. R.M. Ion, D. Frackowiak, A. Planner, K. Wiktorowicz, Acta Biochim. Pol. 45, 833 (1998)
8. T. Hideo, Jpn. Tokkyo Koho JP567 005480, 1981, 14. Chem. Abstr. 95, 80922b (1981)
9. C.G. Knight, T. Stephens, Biochem. J. 258, 683 (1989)
10. P.V. Shinde, A.H. Kategaonkar, B.B. Shingate, M.S. Shingare, Beilstein J. Org. Chem. 7, 53 (2011)
11. A. Khazaei, A.R. Moosavi-Zare, Z. Mohammadi, A. Zare, V. Khakyzadeh, G. Darvishi, RSC Adv. 3,
1323 (2013)
12. A. Hasaninejad, M. Dadar, A. Zare, Chem. Sci. Trans. 1, 233 (2012)
13. E. Mosaddegh, M.R. Islami, A. Hassankhani, Arab J. Chem. 5, 77 (2012)
14. B. Maleki, M. Gholizadeh, Z. Sepehr, Bull. Korean Chem. Soc. 32, 1697 (2011)
15. M. Seyyed hamzeh, P. Mirzaei, A. Bazgir, Dyes Pigm. 76, 836 (2008)
16. G. Song, B. Wang, H. Luo, L. Yang, Catal. Commun. 8, 673 (2007)
17. F. Shirini, G.H. Imanzadeh, M. Abedini, M.A. Dokhte-Ghaziani, P.G. Ghasemabadi, M.S. Langroodi,
Iran. J. Catal. 2, 115 (2012)
18. S. Kantevari, R. Bantu, L. Nagarapu, ARKIVOC 14, 136 (2006)
19. H.R. Shaterian, A. Hosseinian, M. Ghashang, Turk. J. Chem. 33, 233 (2009)
20. M.A. Zolfigol, V. Khakyzadeh, A.R. Moosavi-Zare, A. Zare, S.B. Azimi, Z. Asgari, A. Hasaninejad,
C. R. Chimie 15, 719 (2012)
123

A. Khazaei et al.
21. A. Zare, A.R. Moosavi-Zare, M. Merajoddin, M.A. Zolfigol, T. Hekmat-Zadeh, A. Hasaninejad, A.
Khazaei, M. Mokhlesi, V. Khakyzadeh, F. Derakhshan-Panah, M.H. Beyzavi, E. Rostami, A.
Arghoon, R. Roohandeh, J. Mol. Liq. 167, 69 (2012)
22. A. Hasaninejad, M. Shekouhy, M. Miar, S. Firoozi, Synth. React. Inorg. Met. Org. Nano Met. Chem.
46, 151 (2016)
23. E. Kolvari, A. Ghorbani-Choghamarani, P. Salehi, F. Shirini, M.A. Zolfigol, J. Iran. Chem. Soc. 4,
126 (2007)
24. A. Khazaei, A. Alizadeh, R. Ghorbani-Vaghei, Molecules 6, 253 (2001)
25. A. Khazaei, A. Raiatzadeh, A. Rostami, J. Chin. Chem. Soc. 54, 465 (2007)
26. A. Khazaei, F. Abbasi, A.R. Moosavi-Zare, RSC Adv. 4, 1388 (2014)
27. A. Khazaei, F. Abbasi, M. Kiani Borazjani, S. Saednia, J. Braz. Chem. Soc. 25, 361 (2014)
28. A. Khazaei, F. Abbasi, A.R. Moosavi Zare, N. J. Chem. 38, 5287 (2014)
29. S. Habibzadeh, H. Ghasemnejad-bosra, J. Chin. Chem. Soc. 58, 1 (2011)
30. S.F. Hojati, M. Gholizadeh, M. Haghdoust, F. Shafiezadeh, Bull. Korean Chem. Soc. 31, 3238 (2010)
123