An efficient heterogeneous iron oxide nanoparticle catalyst for the synthesis of 9-substituted xanthene-1,8-dione

Article abstract of DOI:10.1007/s11164-020-04112-z

Abstract: An efficient and simple method for the synthesis of xanthene derivatives by using iron oxide nanoparticles (NPs) as a catalyst has been investigated. Synthesis of 9-substituted xanthene-1,8-dione derivatives involves one-pot reaction of dimedone

Full text of DOI:10.1007/s11164-020-04112-z

Research on Chemical Intermediates
https://doi.org/10.1007/s11164-020-04112-z
An efcient heterogeneous iron oxide nanoparticle catalyst
ꢀor the synthesis oꢀ 9‑substituted xanthene‑1,8‑dione
Dhakshanamurthy Thirumalai1 · Shanmugam Gajalakshmi1
Received: 21 November 2019 / Accepted: 17 February 2020
©
Springer Nature B.V. 2020
Abstract
An efcient and simple method ꢀor the synthesis oꢀ xanthene derivatives by using
iron oxide nanoparticles (NPs) as a catalyst has been investigated. Synthesis oꢀ
9
-substituted xanthene-1,8-dione derivatives involves one-pot reaction oꢀ dimedone
and aldehyde in the presence oꢀ iron oxide nanoparticles using polar protic ethanol
as a solvent. Interestingly, this catalyst has been recovered by simple ꢁltration and
reused ꢀor up to ꢁve cycles without much loss oꢀ its productivity. The merits oꢀ this
protocol are cost-eꢂectiveness oꢀ the catalyst, having no harmꢀul side products, sim-
ple process, short reaction time, convenient product isolation and potential yields.
Graphic abstract
Electronic supplementary material The online version oꢀ this article (https://doi.org/10.1007/s1116
4
-020-04112-z) contains supplementary material, which is available to authorized users.
*
Dhakshanamurthy Thirumalai
thirumalaid@tvu.edu.in
1
Department oꢀ Chemistry, Thiruvalluvar University, Vellore, Tamil Nadu 632 115, India
Vol.:(012
1
3456789)
3

D. Thirumalai, S. Gajalakshmi
Keywords Iron oxide nanoparticle · Xanthene-1,8-diones · Catalyst · Schiꢂ base
Introduction
The xanthene derivatives attract much attention due to their diverse biological
displays such as antioxidant [1, 2], antileukemic [3], antimicrobial [4, 5], insec-
ticidal [6], antiꢀungal [7], antimycobacterial [8], antiplasmodial [9–11], antitu-
mor [9], apoptotic [12], antiproliꢀerative [13], antimalarial [14], anticancer [15],
antinociceptive [16], anti-inꢃammatory [17–19] and antiviral [20, 21] activities.
Indigofera longeracemosa is a natural source oꢀ xanthene dye [22]. Several syn-
thesis methods oꢀ xanthenes enhanced by various catalysts such as multiwalled
carbon nanotubes anchored by ruthenium [23], homogeneous catalyst oꢀ ruthe-
nium chloride hydrate [24], tetrachlorosilane [25], ceric ammonium nitrate sup-
ported HY-zeolite [26], ionic liquid [NMP]·H PO [27], rice husk [28], succin-
2
4
imide-N-sulꢀonic acid [29], tetradecyltrimethylammonium bromide (TTAB) [30],
Bronsted acidic ionic liquids [31], guanidine hydrochloride [32], nanoparticle
silica-supported sulꢀuric acid (NPs SiO -H SO ) [33], tetrapropylammonium bro-
2
2
4
mide [34], [CTA]Fe/MCM-41 [35], sulꢀated polyborate [36], cellulose sulꢀonic
acid [37], ZrOCl ·8H O [38], heterogeneous silica-bonded imidazolium–sulꢀonic
2
2
acid chloride [39], basic ionic liquid ꢀrom ethane-1,2-diyl bis (hydrogen sulꢀate),
DBU (1,8-diazabicyclo[5.4.0]undec-7-ene) [40] and Sncl ·5H O [41] are well
4
2
documented in the literature. The signiꢁcance oꢀ supported iron oxide nanoparti-
cles in various syntheses oꢀ organic compounds is shown in Table 1. Conversely,
the potential efcacy oꢀ the above-mentioned catalysts ꢀor the synthesis oꢀ xan-
thenes possesses their own disadvantages, including stumpy yields oꢀ products,
lengthy reaction times, ꢀar-reaching reaction conditions, monotonous work-up
procedures or luxurious reagents. Moreover, in the majority oꢀ the reported tech-
niques, the catalysts are not recyclable. However, in the present work, we have
reported the one-pot synthesis oꢀ 9-substituted xanthene-1,8-diones by using iron
oxide nanoparticles as a recyclable catalyst.
Table 1 Synthesis oꢀ xanthenes, diazepines, pyrimidines and pyridines by solid-supported iron nanocom-
posites
S. no
Catalyst
Compounds
Reꢀerences
1
2
3
4
Fe O @chitosan
Xanthenes
Diazepines
Pyrimidines
Pyridine
[44]
[45]
[46]
[47]
3
4
Fe O /SiO
3
4
2
Cellulose/Fe O /Ag
2
3
Fe O /SiO /propyltriethoxy silane/L-pro-
3
4
2
line (LPSF) nanoparticles
CuFe O @HNTs
5
Pyrazolopyridine
[48]
2
4
1
3

An efcient heterogeneous iron oxide nanoparticle catalyst…
Results and discussion
In this present work, efcient protocol ꢀor the synthesis oꢀ 9-substituted xanthene-
1
,8-diones (3a–j) was achieved by using iron oxide nanoparticles as a heterogene-
ous catalyst. Initially, various reaction conditions (as listed in Table 2) were tried
or the synthesis oꢀ 9-substituted xanthene-1,8-diones (3a–j) ꢀrom dimedone and
ꢀ
substituted aldehydes. Among all, the iron oxide NPs’ catalytic reaction in ethanol
was ꢀound to be more efcient based on the reaction yield. The catalyst, iron oxide
NPs, was prepared by stirring a solution oꢀ 0.1 M ꢀerric chloride with an aqueous
extract oꢀ leaves oꢀ Raphanus sativa at room temperature ꢀor an hour [42]. The sche-
matic representation oꢀ catalyst preparation is shown in Scheme 1. The optimization
oꢀ iron oxide NPs catalyst required ꢀor better yield was also perꢀormed as given in
Table 3. From the table, it was evident that 15 mol% oꢀ the catalyst in polar protic
solvent resulted in considerably good yield. Also, the beneꢁt oꢀ greener iron oxide
(
Fe O ) was compared with other articles as shown in Table 4.
2 3
At the onset, the synthesis oꢀ xanthene-1,8-dione (Scheme 2) was carried out by
the reaction oꢀ dimedone (2 equiv.) and various aldehydes (1 equiv.) in the presence
Table 2 Reaction condition optimization ꢀor the synthesis oꢀ xanthene-1,8-diones
Method/catalysta
Solvent
Time
Yield (%)
b
Entry
1
2
3
4
5
6
7
8
9
Grinding
–
1 h
1 h
–
20
14
37
Ultrasonication
Microwave (210 W)
Microwave (210 W)
Microwave (210 W)
Stirring
Stirring
Stirring
Stirring/iron oxide NPs
Ethanol
–
Methanol
Ethanol
–
1% acidic water
Ethanol
Ethanol
8 min
30 min
45 min
10 min
10 min
10 min
2 h
48
No change
12
22
85
a
Reaction oꢀ dimedone and benzaldehyde
Isolated yield
b
1
hr
Radish leaves
extract
Iron oxide
nanoparticles
+
Fecl (0.1 M)
3
stirring
Scheme 1 Synthesis oꢀ iron oxide nanoparticles
Table 3 Quantity oꢀ catalyst
a
S. no
Mol % oꢀ catalyst
Time
Yield (%)
required
1
2
3
4
5
10
15
20
60
60
60
60
50
65
85
85
aIsolated yield
1
3

D. Thirumalai, S. Gajalakshmi
Table 4 Comparison oꢀ Fe O catalyst in the synthesis oꢀ xanthene-1,8-diones
2
3
S. No
Catalyst
Fe O @SiO –SnCl
4
Condition
Time
Yield (%)
Reꢀerences
1
Ultrasonic irradia- Appropriate
tion (50 W)
90
[42]
3
4
2
2
3
Fe O @SiO –SO H
Reꢃux (130 °C)
Stirred/ethanol
35 min
2 h
90
90
[43]
This work
3
4
2
3
Fe O nanoparticles
2
3
O
O
R
O
O
O
Ethanol
+
O
2
R
H
Iron oxide
nano particle
Stirred
1
2 (a-j)
3
(a-j)
Scheme 2 Synthesis oꢀ 9-substituted xanthene-1,8-diones 3a–j
oꢀ iron oxide nanoparticles in ethanol by stirring at room temperature. All the deriv-
atives (Fig. 1) were puriꢁed through recrystallization in ethanol and were character-
1
13
ized by FTIR, H NMR, C NMR and HRMS spectral techniques.
The structure oꢀ the xanthene derivative 3h was also conꢁrmed by single-crystal
XRD analysis. The diꢂraction intensity data were collected ꢀor the space group P2 /n
1
oꢀ the crystallized title compound through Bruker AXS area detector. The random
structure obtained by direct methods with reliable index value was 0.18 ꢀor 27 sur-
2
viving atoms and reꢁned with F by ꢀull-matrix least square methods. All hydrogen
atoms were allowed to ꢁx by geometrically corresponding to parent carbon atoms.
The reꢁned R value received at the end oꢀ reꢁnement cycle was 7.9%, and Ortep
plot drawn at 30% probability oꢀ crystal structure is displayed in Fig. 2. The outer
rings A & C adopted envelope conꢀormation which is conꢁrmed by the total pucker-
ing amplitudes and (Cremer & Pople, 1975) [Q =0.4470 Å and 0.4688 Å ꢀor rings
T
A & C, respectively]. In the central ring B, C1 had slight deviation appeared by
−
0.091(1)Å, which is conꢁrmed ꢀrom least-square plane calculation value (Nardelli
et al. 1965). The crystal packing was stabilized by van der Waals interaction, and
the molecule exhibited intramolecular C–H⋯π interaction between C15 and ring C
[
C14–C19] through H15 atom with 2.68 Å by 104° angle.
Aꢀter the synthesis oꢀ 4-nitrosubstituted xanthene-1,8-dione, nitroreduction was
carried out in the presence oꢀ Zn/Cacl in ethanol under reꢃux. Further, the syn-
2
thesized 4-aminophenyl-xanthene-1,8-dione was coupled with diꢂerent aldehydes in
ethanol using sodium acetate (20 mol%) as a catalyst (Scheme 3).
The plausible mechanism ꢀor the synthesis oꢀ xanthenes in the presence oꢀ
iron oxide nanoparticles can be visualized as shown in Fig. 3. Initial activation
oꢀ the carbonyl group oꢀ aldehyde 2 by Fe produced an intermediate I. Then,
two nucleophilic attacks by dimedone 1 with loss oꢀ two molecules oꢀ water
successively ꢀormed an intermediate II, which underwent dehydration to aꢂord
the desired product 3. The heterogeneous reaction phase oꢀ iron oxide catalyst
used in the synthesis oꢀ 9-substituted xanthenes-1,8-diones was easy to use ꢀor
1
3

An efcient heterogeneous iron oxide nanoparticle catalyst…
OCH3
Cl
O
O
O
O
O
CH3 O
O
O
O
O
O
O
(
3a) 2 hr 15 min ( 80%)
m.p. 238 - 240 °C
Lit. 240-242 °C [49]
(3b) 2 hr 30 min ( 77%) (3c) 3 hr 15 min ( 70%)
(
3d) 2 hr 45 min ( 82%)
m.p. 205- 207 °C
Lit. 204-206 °C [49]
m.p. 230-232 °C
m.p. 130--132 °C
Lit. 229-230 °C [49]
Lit. 129-131 °C [50]
OH
CH3
OCH3
S
O2N
O
O
O
O
O
O
O
O
O
O
O
O
(
3e) 3 hr ( 75%)
(3f) 1 hr 50 min ( 81%) (3g) 3 hr 15 min ( 85%) (3h) 2 hr 30 min ( 88%)
m.p. 223-225 °C
m.p. 140-142 °C
m.p. 246-248 °C
m.p. 218-220 °C
Lit. 225-227 °C [51]
Lit. 142-144 °C[52]
Lit. 248 - 249 °C [49]
Lit. 217 - 218 °C [49]
OH
NO2
HO
N
O
O
O
O
O
O
O
O
(
3i) 3 hr 20 min ( 72%)
m.p. 245-247 °C
Lit. 247 - 248 °C [49]
(3j) 2 hr 15 min ( 90%)
m.p. 218-220 °C
Lit. 221 - 223 °C [49]
O
6
(70%); m.p. 220 - 222 °C
Fig. 1 Reaction time, percentage yield and melting point oꢀ xanthene-1,8-diones (3a–j) and 6
another cycle, and the catalyst recyclability is shown in Fig. 4. In view oꢀ reac-
tivity, xanthene containing electron-withdrawing moiety comparatively ꢀormed
higher yield than the compounds having electron-donating moiety.
Experimental
Preparation of iron oxide nanoparticles
Radish (Raphanus sativus) leaves extract (2 equiv.) was stirred with 0.1 M FeCl
3
(
1 equiv.) solution under room temperature ꢀor an hour. Then, the reaction mix-
ture was dried at 300 °C ꢀor 3 h to get iron oxide nanoparticles [53].
1
3

D. Thirumalai, S. Gajalakshmi
Fig. 2 ORTEP diagram oꢀ compound 3h
Scheme 3 Synthesis oꢀ 9-(4-(((2-hydroxynaphthalen-1-yl)methylene)amino)phenyl)-3,3,6,6-tetramethyl-
,4,5,6,7,9-hexahydro-1H-xanthene-1,8(2H)-dione 6
3
A general procedure for the production of xanthene‑1,8‑dione compounds 3(a–j)
A mixture oꢀ aldehyde (1 mmol), dimedone (2 mmol) and iron oxide nanoparti-
cles (0.1 mmol) as a catalyst was stirred at room temperature ꢀor 2 h in ethanol
(
20 mL). The ꢀorward movement oꢀ the reaction was monitored by TLC. Aꢀter
completion oꢀ the reaction, the catalyst was removed by using Whatman ꢁlter
paper, and in some cases, the suspended nanoparticle was removed by centriꢀuga-
tion method. Then, the crude product was recrystallized ꢀrom ethanol to ꢀorm a
1
3

An efcient heterogeneous iron oxide nanoparticle catalyst…
Fig. 3 Plausible mechanistic pathway oꢀ 9-substituted xanthene-1,8-diones (3a–n)
100
80
60
3d
4
0
3i
3j
2
0
3j
0
NEW
3d
I
II
Catalyst running counts
III
IV
Fig. 4 Catalyst recyclability chart ꢀor 3d, 3i and 3j
1
3

D. Thirumalai, S. Gajalakshmi
pure crystal oꢀ the 9-substituted xanthene-1,8-diones (3a–j). The catalyst used in
the reaction was reusable ꢀor up to 5 cycles (as shown in Fig. 4).
A general procedure for the production of 9‑(4‑(((2‑hydroxynaphthalen‑1‑yl)
methylene)amino)phenyl‑xanthene‑1,8(2H)‑dione 6
Compound 3j was reduced by using Zn and Cacl using ethanol as a solvent under
2
reꢃux ꢀor 8 h. The reaction progress was monitored by TLC. Then, the reaction mix-
ture was ꢁltered (ꢀor removing Zn and ZnO) and poured into ice-cold water to get
9
-(4-aminophenyl)-xanthene-1,8-dione. Further, it was condensed with 2-hydroxy
naphthaldehyde to get xanthene Schiꢂ base.
3
,4,6,7‑Tetrahydro‑9‑(4‑methoxyphenyl)‑3,3,6,6‑tetramethyl‑2H‑xan‑
−
1
thene‑1,8(5H,9H)‑dione 3a Pale yellow crystals; IR (KBr, cm ) v : 2968
max
1
(
–CH), 1668 (–C=O), 1464 (C=C), 1183 (–C–O); H NMR (300 MHz, CDCl ):
3
δ 0.99 and 1.09 (2 s, 12H, gem-dimethyl), 2.18–2.20 (2d, 4H, C and C –CH ,
4
5
2
J= 6.9 Hz), 2.45 (s, 4H, C and C –CH ) 3.72 (s, 3H, –OCH ), 4.69 (s, 1H,
2
7
2
3
1
3
C –H), 6.75 (d, 2H, ArH, J= 8.7 Hz), 7.2 (d, 2H, ArH, J= 8.7 Hz); C NMR
9
(
75 MHz,CDCl ): δ 196.51, 162.09, 157.96, 136.49, 129.31, 115.79, 113.47, 55.10,
3
5
2
0.77, 40.86, 32.19, 30.96, 29.27, 27.34; DEPT-135: 129.31, 113.46, 55.11, 30.96,
+
9.28, 27.34 (CH↑,CH ↑); 50.77, 40.86 (CH ↓); HRMS (EI ): Calcd. ꢀor C H O
3
2
24 28
4
+
+
m/z 380.1987[M ]; ꢀound m/z 380.1983[M ].
9
‑(4‑Chlorophenyl)‑3,4,6,7‑tetrahydro‑3,3,6,6‑tetramethyl‑2H‑xan‑
−
1
thene‑1,8(5H,9H)‑dione 3b White powder; IR (KBr, cm ) v : 2954 (–CH),
max
1
1
1
2
654 (–C=O), 1457 (C=C), 1190 (–C–O); H NMR (400 MHz, CDCl ): δ 0.97 and
3
.09 (2 s, 12H, gem-dimethyl), 2.13–2.24 (2d, 4H, C and C –CH , J= 12 Hz),
4
5
2
.45 (s, 4H, C and C –CH ), 4.69 (s, 1H, C –H), 7.16 (d, 2H, ArH, J= 6 Hz), 7.23
2
7
2
9
1
3
(
d, 2H, ArH, J= 6 Hz); C NMR (75 MHz, CDCl ): δ 196.35, 162.45, 142.70,
3
1
1
32.03, 129.77, 128.21, 115.28, 50.70, 40.86, 32.19, 31.47, 29.26, 27.29; DEPT-
35: 129.77, 128.21, 31.46, 29.27, 27.29 (CH↓,CH ↓); 40.85, 50.69(CH ↑); HRMS
3
2
+
+
+
(
EI ): Calcd. ꢀor C H ClO m/z 384. 1492[M ]; ꢀound m/z 384.1483[M ].
23 25 3
3
3
,4,6,7‑Tetrahydro‑3,3,6,6,9‑pentamethyl‑2H‑xanthene‑1,8(5H,9H)‑dione
−1
c Halꢀ white shining powder; IR (KBr, cm ) v : 2962 (–CH), 1654 (–C=O),
max
1
1
457 (C=C), 1211 (–C–O); H NMR (300 MHz, CDCl ): δ 1.08 and 1.10 (2 s, 12H,
3
gem-dimethyl), 2.27 and 2.35 (2 s, 8H, C , C and C , C –CH ), 3.64 (s, 3H, –CH ),
4
5
2
7
2
3
1
3
δ 7.27 (s, 1H, C –H); C NMR (75 MHz, CDCl ): δ 197.08, 162.72, 116.75, 50.96,
9
3
4
2
2
0.84, 32.07, 29.25, 27.21, 21.74, 20.86; DEPT-135: 32.03, 29.25, 27.21, 21.74,
+
0.86 (CH↓,CH ↓); 50.95, 40.83 (CH ↑); HRMS (EI ): Calcd. ꢀor C H O m/z
3
2
18 24
3
+
+
88.1725[M ]; ꢀound m/z 288.1711 [M ].
3
, 4 , 6 , 7 ‑Te t r a h y d r o ‑ 3 , 3 , 6 , 6 ‑ t e t r a m e t h y l ‑ 9 ‑ p h e n y l ‑ 2 H ‑ x a n ‑
−
1
thene‑1,8(5H,9H)‑dione 3d White powder; IR (KBr, cm ) v : 2954 (–CH),
max
1
1
654 (–C=O), 1549 (C=C), 1288 (–C–O); H NMR (300 MHz, CDCl ): δ 0.98
3
1
3

An efcient heterogeneous iron oxide nanoparticle catalyst…
and 1.09 (2 s, 12H, gem-dimethyl), 2.17 (2d, 4H, C and C –CH , J= 13.8 Hz),
4
5
2
1
3
2
.46 (s, 4H, C and C –CH ), 4.75 (s, 1H, C –H), 7.09–7.29 (m, 5H, ArH);
C
2
7
2
9
NMR (75 MHz, CDCl ): δ 196.40, 162.26, 144.07, 128.38, 128.03, 126.36,
3
1
2
3
15.69, 50.75, 40.89, 32.19, 31.83, 29.25, 27.33; DEPT-135: 126.38, 31.83, 29.27,
+
7.34 (CH↓,CH ↓); 50.74, 40.89 (CH ↑); HRMS (EI ): Calcd. ꢀor C H O m/z
3
2
23 26
3
+
+
50.1881[M ]; ꢀound m/z 350.1871[M ].
3
,4,6,7‑Tetrahydro‑9‑(4‑hydroxy‑3‑methoxyphenyl)‑3,3,6,6‑tetrame‑
−
1
thyl‑2H‑xanthene‑1,8(5H,9H)‑dione 3e Light brown powder; IR (KBr, cm )
1
v
: 3390 (–OH), 2962 (–CH), 1654 (–C=O), 1521 (C=C), 1358 (–C–O); H NMR
max
(
300 MHz, CDCl ): δ 0.99 and 1.09 (2 s, 12H, gem-dimethyl), 2.19 (2d, 4H, C
3
4
and C –CH , J= 15 Hz), 2.44 (s, 4H, C and C –CH ), 3.88 (s, 3H, –OCH3),
5
2
2
7
2
4
.74 (bs, 1H, –OH), 5.45 (s, 1H, C –H), 6.56 (d,1H, ArH, J= 6 Hz), 6.715 (d, 1H,
9
1
3
ArH, J= 9 Hz), 6.99 (s, 1H, ArH); C NMR (75 MHz, CDCl ): δ 196.64, 162.10,
3
+
1
45.89, 136.47, 115.92, 55.89, 40.87, 32.81, 31.32, 29.23, 27.29; HRMS (EI ):
+
+
Calcd. ꢀor C H O m/z 396.1936 [M ]; ꢀound m/z 396.1925 [M ].
2
4
28
5
3
,4,6,7‑Tetrahydro‑3,3,6,6‑tetramethyl‑9‑(thiophen‑2‑yl)‑2H‑xan‑
−
1
thene‑1,8(5H,9H)‑dione 3f Black powder; IR (KBr, cm ) v : 2962 (–CH),
max
1
1
1
5
1
2
5
661 (–C=O), 1619(C=C), 1190 (–C–O); H NMR (300 MHz, CDCl ): δ 1.05 and
3
.10 (2 s, 12H, gem-dimethyl), 2.25 and 2.45 (2 s, 8H, C , C and C , C –CH ),
4
5
2
3
7
2
1
3
.14 (s, 1H, C –H), 6.8–7.26 (m, 3H, ArH); C NMR (75 MHz, CDCl ): δ 196.30,
9
62.70, 148.12, 126.75, 125.32, 123.37, 115.27, 50.74, 40.85, 32.13, 29.35, 27.35,
6.37; DEPT-135: 126.76, 125.32, 123.39, 29.36, 28.57, 27.35, 26.36 (CH↓,CH ↓);
3
+
+
0.73, 40.84 (CH ↑); HRMS (EI ): Calcd. ꢀor C H O S m/z 356.1446 [M ]; ꢀound
2
21 24
3
+
m/z 356.1435 [M ].
3
,4,6,7‑Tetrahydro‑3,3,6,6‑tetramethyl‑9‑(2‑nitrophenyl)‑2H‑xan‑
−
1
thene‑1,8(5H,9H)‑dione 3g Brownish orange powder; IR (KBr, cm ) v
:
max
−
1
2
954 (–CH), 1661 (–C=O, 1558 (-N–O ), 1521 (C=C), 1211 (–C–O); H NMR
(
300 MHz, CDCl ): δ 1.00 and 1.09 (2 s, 12H, gem-dimethyl), 2.21 (2d, 4H, C and
3
4
C –CH , J=16.2), 2.47 (s, 4H, C and C –CH ), 5.52 (s, 1H, C –H), 7.00–7.77 (m,
5
2
2
7
2
9
1
3
4
1
1
H, ArH); C NMR (75 MHz, CDCl ): δ 196.40, 163.05, 149.87, 137.94, 131.95,
3
31.17, 127.21, 124.63, 114.17, 50.61, 40.86, 32.06, 28.92, 27.61; DEPT-135:
31.97, 131.16, 127.22, 124.63, 28.93, 27.61 (CH↓,CH ↓); 50.61, 40.85 (CH ↑);
3
2
+
+
+
HRMS (EI ): Calcd. ꢀor C H NO m/z 395.1732 [M ]; ꢀound m/z 395.1745 [M ].
2
3
25
5
3
, 4 , 6 , 7 ‑Te t r a h y d r o ‑ 3 , 3 , 6 , 6 ‑ t e t r a m e t h y l ‑ 9 ‑ p ‑ t o l y l ‑ 2 H ‑ x a n ‑
−
1
thene‑1,8(5H,9H)‑dione 3h White powder; IR (KBr, cm ) v : 2962 (–CH),
max
1
1
1
661 (–C=O, 1499 (C=C), 1197 (–C–O); H NMR (300 MHz, CDCl ): δ 0.99 and
3
.09 (2 s, 12H, gem-dimethyl), 2.2 (2d, 4H, C and C –CH , J= 6.7 Hz), 2.45
4
5
2
(
s, 4H, C and C –CH ), 2.23 (s, 3H,–CH ), 4.70 (s, 1H, C –H), 7 (d, 2H, ArH,
2 7 2 3 9
1
3
J=7.5), 7.16 (d, 2H, ArH, J=7.5); C NMR (75 MHz, CDCl ): δ 196.41, 162.10,
3
1
2
41.19, 135.77, 128.78, 128.24, 115.79, 50.78, 40.89, 32.19, 31.44, 29.25, 27.38,
1.04; DEPT-135: 128.78, 128.25, 31.44, 29.25, 27.38, 21.04 (CH↓,CH ↓); 50.78,
3
1
3

D. Thirumalai, S. Gajalakshmi
+
+
4
0.89 (CH ↑); HRMS (EI ): Calcd. ꢀor C H O m/z 364.2038 [M ]; ꢀound m/z
2
24 28
3
+
3
64.2033 [M ].
3
,4,6,7‑Tetrahydro‑9‑(4‑hydroxyphenyl)‑3,3,6,6‑tetramethyl‑2H‑xan‑
−
1
thene‑1,8(5H,9H)‑dione 3i Brown solid; IR (KBr, cm ) v : 3425(–OH), 2954
max
1
(
–CH), 1626 (–C=O, 1464 (C=C), 1232 (–C–O); H NMR (300 MHz, CDCl ): δ
3
0
.99 and 1.08 (2 s, 12H, gem-dimethyl), δ 2.19 (2d, 4H, C and C –CH J=4.5 Hz),
4 5 2,
δ 2.44 (s, 4H, C and C –CH ), δ 4.67 (s, 1H, C -H), δ 6.56 (d, 2H, ArH, J=
2
7
2
9
1
3
1
1
2
.8 Hz), δ 7.07 (d, 2H, ArH, J= 2.1 Hz); C NMR (75 MHz,CDCl ): δ 196.74,
3
62.21, 154.55, 135.90, 129.36, 115.96, 115.17, 50.83, 40.94, 32.15, 30.98, 29.09,
7.37; DEPT-135: 50.83, 40.94 (CH2↑); 129.36, 115.96, 30.98, 29.09, 27.37(CH↓,
+
+
CH ↓); HRMS (EI ): Calcd. ꢀor C H O m/z 366.1831 [M ]; ꢀound m/z 366.1830
3
23 26
4
+
[
M ].
3
,4,6,7‑Tetrahydro‑3,3,6,6‑tetramethyl‑9‑(4‑nitrophenyl)‑2H‑xan‑
−
1
thene‑1,8(5H,9H)‑dione 3j Pale yellow powder; IR (KBr, cm ) v : 2968 (–CH),
max
1
1
1
2
661 (–C=O, 1466 (C=C), 1197 (–C–O); H NMR (300 MHz, CDCl ): δ 0.99 and
3
.11 (2 s, 12H, gem-dimethyl), δ 2.20 (2d, 4H, C and C –CH , J= 11.7 Hz), δ
4
5
2
.49 (s, 4H, C and C –CH ), δ 4.83 (s, 1H, C -H), δ 7.46 (d, 2H, ArH, J= 8.7 Hz),
2
7
2
9
1
3
δ 8.07 (d, 2H, ArH, J= 8.7 Hz); C NMR (75 MHz, CDCl ): δ 195.94, 162.82,
3
1
51.40, 146.63, 129.31, 123.33, 114.63, 50.65, 40.92, 32.36, 32.14, 29.12, 27.29;
DEPT-135: 129.31, 123.33, 32.36, 29.12, 27.29 (CH↓,CH ↓); 50.65, 40.92(CH ↑);
3
2
+
+
+
HRMS (EI ): Calcd. ꢀor C H NO m/z 395.1732 [M ]; ꢀound m/z 395.1749 [M ].
2
3
25
5
(
E ) ‑ 9 ‑ ( 4 ‑ ( ( ( 2 ‑ h y d r o x y n a p h t h a l e n ‑ 1 ‑ y l ) m e t h y l e n e ) a m i n o )
p h e ny l ) ‑ 3 , 3 , 6 , 6 ‑ t e t r a m e t hy l ‑ 3 , 4 , 5 , 6 , 7 , 9 ‑ h e x a hyd r o ‑ 1 H ‑ x a n ‑
−
1
thene‑1,8(2H)‑dione (6) Brick red solid; IR (KBr, cm ) v : 3416 (–OH), 1635
max
1
(
–C=O, 1373 (C=N), 1120 (–C–O); H NMR (400 MHz, CDCl ): δ 0.99 and 1.10
3
(
2 s, 12H, gem-dimethyl), 2.14–2.26 (2d, 4H, C and C –CH , J=16.4), 2.48 (s, 4H,
4
5
2
1
3
C and C –CH ), 4.81 (s, 1H, C -H), 6.9–7.8 (m, 6H, ArH), 8.01 (s, 1H,–CH);
C
2
7
2
9
NMR (75 MHz,CDCl ): δ 196.46, 171.22, 162.43, 153.95, 142.99, 136.71, 133.36,
3
1
2
29.73, 128.08, 127.17, 123.42, 119.96, 115.37, 108.69, 50.76, 40.90, 32.24, 31.93,
+
+
9.69, 27.36, 14.11; HRMS (EI ): Calcd. ꢀor C H NO m/z 519.2410 [M ]; ꢀound
3
4
33
4
+
m/z 519.2398 [M ].
Conclusion
In summary, we have reported a simple method oꢀ synthesis oꢀ xanthene-1,8-diones
by treating dimedone and aldehyde in the presence oꢀ iron oxide nanoparticle cata-
lyst using ethanol as a solvent. In this context, we have ꢀound a green method ꢀor the
synthesis oꢀ xanthene-1,8-dione derivatives, and the advantages oꢀ this procedure
include high yields, operational simplicity and environmentally ꢀriendly procedure.
Acknowledgements We grateꢀully thank the Department oꢀ Science and Technology (DST), Govern-
ment oꢀ India, ꢀor DST-INSPIRE ꢀellowship (DST/INSPIRE Fellowship/2016/IF160736). We also
1
3

An efcient heterogeneous iron oxide nanoparticle catalyst…
acknowledge VIT-SAIF ꢀor NMR, IIT Madras and University oꢀ Madras ꢀor HRMS and single crystal
XRD ꢀacility.
Compliance with ethical standards
Conꢁicts oꢀ interest The authors have no conꢃicts oꢀ interest.
References
1
2
3
.
.
.
N. Hashim, M. Rahmani, M.A. Sukari, A.M. Ali, N.B. Alitheen, R. Go, H.B.M. Ismail, J. Asian
Nat. Prod. Res. 12, 106 (2010)
A.E. Hay, M.C. Aumond, S. Mallet, V. Dumontet, M. Litaudon, D. Rondeau, P. Richomme, J. Nat.
Prod. 67, 707 (2004)
S. L. Niu, Z. L. Li, F. Ji, G. Y. Liu, N. Zhao, X. Q. Liu, Y. K. Jing, H. M. Hua, Phytochemistry. 77,
2
80 (2012)
4
5
6
.
.
.
C.G. Knight, T. Stephens, Biochem. J. 258(3), 683 (1989)
P. Moosophon, S. Kanokmedhakul, K. Kanokmedhakul, K. Soytong, J. Nat. Prod. 72, 1442 (2009)
J.M. Khurana, D. Magoo, K. Aggarwal, N. Aggarwal, R. Kumar, C. Srivastava, Eur. J. Med. Chem.
5
8, 470 (2012)
7
.
G.L. Djouꢀack, K.M.V. Vetschera, J. Schinnerl, L. Brecker, E. Lorbeer, W. Robien, Nat. prod. Com-
mun. 5, 1055 (2010)
8
9
.
.
P. Moosophon, S. Kanokmedhakul, K. Kanokmedhakul, K. Soytong, J. Nat. Prod. 72, 117 (2008)
S.J. Tao, S.H. Guan, W. Wang, Z.Q. Lu, G.T. Chen, N. Sha, Q.X. Yue, X. Liu, D.A. Guo, J. Nat.
Prod. 72, 117 (2009)
1
1
1
1
1
1
0. A.G. Azzebaze, M. Meyer, A. Valentin, E.L. Nguemꢀo, Z.T. Fomum, A.E. Nkengꢀack, Chem.
Pharm. Bull. 54, 111 (2006)
1. F. Zeleꢀack, D. Guilet, N. Fabre, C. Bayet, S.V. Chevalley, S.R. Ngouela, B.N. Lenta, A. Valentin, E.
Tsamo, M.G.V.D. Franca, J. Nat. Prod. 72, 954 (2009)
2. Q.B. Han, H.L. Tian, N.Y. Yang, C.F. Qiao, J.Z. Song, D.C. Chang, K.Q. Luo, H.X. Xu, Chem. Bio-
divers. 5, 2710 (2008)
3. S. Cao, P.J. Brodie, J.S. Miller, R. Randrianaivo, F. Ratovoson, C. Birkinshaw, R. Andriantsiꢀerana,
V.E. Rasamison, D.G.I. Kingston, J. Nat. Prod. 70, 679 (2007)
4. S. Laphookhieo, J.K. Syers, R. Kiattansakul, K. Chantrapromma, Chem. Pharm. Bull. 54, 745
(
2006)
5. K.H. Lee, H.B. Chai, P.A. Tamez, J.M. Pezzuto, G.A. Cordell, K.K. Win, M. Tin Wa, Phytochemis-
try. 64, 535 (2003)
1
1
6. E.F. Llama, C.D. Campo, M. Capo, M. Anadon, Eur. J. Med. Chem. 24, 391 (1989)
7. J.P. Poupelin, G. Saint-Rut, O. Foussard-Blanpin, G. Narcisse, G. Uchida-Ernouꢀ, R. Lacroix, Eur. J.
Med. Chem. 13, 67 (1978)
1
1
2
2
2
2
8. Z.K. Jaberi, M.M. Hashemi, Monatsh. Chem. 139, 605 (2008)
9. A.K. Bhattacharya, K.C. Rana, Mendeleev Commun. 17(4), 247 (2007)
0. R.W. Lambert, J.A. Martin, J.H. Merrett, K.E.B. Parkes, G.J. Thomas, Chem. Abstr. 9, 212 (1997)
1. M. Seyyedhamzeh, M. Mirzaei, A. Bazgir, Dyes Pigm. 76, 836 (2008)
2. J.P. Alcantara-Licudine, M.K. Kawate, Q.X. Li, J. Agric. Food. Chem. 45, 766 (1997)
3. K. Tabatabaeian, A. Khorshidi, M. Mamaghani, A. Dadashi, M.K. Jalali, Can. J. Chem. 89, 623
(
2011)
2
4. K. Tabatabaeian1, M.A. Zanjanchi, M. Mamaghani, A. Dadashi, Res. Chem. Intermed. 42, 5049
(
2015)
2
2
2
2
2
3
3
5. H.A. Soliman, T.A. Salama, Chin. Chem. Lett. 24, 404 (2013)
6. P. Sivaguru, A. Lalitha, Chin. Chem. Lett. 25, 321 (2014)
7. H. Singh, S. Kumari, J.M. Khurana, Chin. Chem. Lett. 25, 1336 (2014)
8. F. Shirini, S.A. Dadamahaleh, A.M. Khah, A.R. Aliakbar, Chimie 16, 207 (2013)
9. F. Shirini, N.G. Khaligh, Dyes Pigm. 95, 789 (2012)
0. P.V. Shinde, A.H. Kategaonkar, B.B. Shingate, M.S. Shingare, Beilstein J. Org. Chem. 7, 53 (2011)
1. H.R. Shaterian, M. Ranjbar, K. Azizi, J. Mol. Liq. 162, 95 (2011)
1
3

D. Thirumalai, S. Gajalakshmi
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
2. M. Sadeghpour, A. Olyaei, M. Rezaei, J. Hetero. Chem. 53, 981 (2016)
3. B. Sadeghi, A. Hassanabadi, E. Taghvatalab, J. Chem. Res. 35, 707 (2011)
4. A.P. Marjani, S. Abdollahi, M. Ezzati, E.N. Kande, J. Hetero. Chem. 55(6), 1324 (2018)
5. M. Pirouzmand, A.M. Gharehbaba, Z. Ghasemi, S.A. Khaaje, Arab. J. Chem. 10(8), 1070 (2016)
6. M.S. Patil, A.V. Palav, C.K. Khatri, G.U. Chaturbhuj, Tetrahedron Lett. 58, 2859 (2017)
7. H.A. Oskooie, L. Tahershamsi, M.M. Heravi, B. Baghernejad, E-J. Chem. 7(3), 717 (2010)
8. E. Mosaddegh, M.R. Islami, A. Hassankhani, Arab. J. Chem. 5, 77 (2012)
9. A.R.M. Zare, M.A. Zolꢁgol, M. Zarei, A. Zare, V. Khakyzadeh, J. Mol. Liq. 211, 373 (2015)
0. B. Maleki, E. Akbarzadeh, S. Babaee, Dyes Pigm. 123, 222 (2015)
1. B. Liang, S. Kalidindi, J.A. Porco, C.R.J. Stephenson, Org. Lett. 12(3), 572 (2010)
2. A. Bamoniri, B.F. Mirjalili, S. Fouladgar, Polycycl. Aromat. Compd. 37, 345 (2017)
3. F. Nemati, S. Sabaqian, J. Saudi. Chem. Soc. 21, S383 (2017)
4. A. Maleki, M. Aghaei, N. Ghamari, Appl. Organometal. Chem. 30, 939 (2016)
5. A. Maleki, Tetrahedron 68, 7827 (2012)
6. A. Maleki, P. Ravaghi, M. Aghaei, H. Movahed, Res. Chem. Intermed. 43, 5485 (2017)
7. A. Maleki, R. Firouzi-Haji, Sci. Rep. 8, 17303 (2018)
8. A. Maleki, Z. Hajizadeh, P. Salehi, Sci. Rep. 9, 5552 (2019)
9. H.N. Karade, M. Sathe, M.P. Kaushik, ARKIVOC 13, 252 (2007)
0. N. Bayou-Khier, M. Amari, M. Fodili, S.G. Grau, P. Hoꢂmann, J. Fundam. Appl. Sci. 8(3), 945
(
2016)
5
5
1. Y.K. Venkatesan, S.S. Pujari, R.J. Lahoti, K.V. Srinivasan, Ultrason. Sonochem. 15, 548 (2008)
2. Z.P. Paliwal, S.R. Jetti, A. Bhatewara, T. Kadre, S. Jain, I.S.R.N. Org, Chem. Article ID 526173, 1
(
2013)
5
3. P. Balu, I.V. Asharani, D. Thirumalai, Unpublished results
Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in published
maps and institutional afliations.
1
3