Microwave-assisted synthesis of 6,6′-(aryl(alkyl)methylene)bis(2,4-dialkylphenol) antioxidants catalyzed by multi-sulfonated reduced graphene oxide nanosheets in water

Article abstract of DOI:10.1039/c4nj02340d

Sulfonated reduced graphene oxide nanosheets (RGO-SO₃H) were characterized using field emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), atomic force microscopy (AFM), Fourier transform infrared spectroscopy (FT-IR), Raman spectroscopy, X-ray diffraction (XRD), thermogravimetric analysis (TGA), and acid-base titration. Multi-SO₃H supported on reduced graphene oxide nanosheets was found to be an efficient catalyst for the green synthesis of 6,6′-(aryl(alkyl)methylene)bis(2,4-dialkylphenol) derivatives from 2,4-dialkylphenols and aromatic and aliphatic aldehydes in aqueous media under microwave irradiation. The synthesis of 6,6′-(aryl(alkyl)methylene)bis(2,4-dialkylphenol) derivatives were carried out in the presence of a catalytic amount of RGO-SO₃H, under thermal and microwave conditions to afford the desired products in high and excellent yields respectively. In addition, the catalyst could be recovered easily and reused several times without any considerable loss of its catalytic activity.

Full text of DOI:10.1039/c4nj02340d

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Page 1 of 37
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DOI: 10.1039/C4NJ02340D
Microwave-assisted synthesis of 6,6′-(aryl(alkyl)methylene)bis(2,4-
dialkylphenol) antioxidants catalyzed by multi sulfonated reduced graphene
oxide nanosheets in water
Hossein Naeimi,* and Mohsen Golestanzadeh
Department of Organic Chemistry, Faculty of Chemistry, University of Kashan, Kashan, 87317,
I. R. Iran
Email: naeimi@kashanu.ac.ir Tel: +98(31)55912388 Fax: +98(31)55912397
Abstract
Sulfonated reduced graphene oxide nanosheets (RGO-SO3H) were characterized by field
emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM),
atomic force microscopy (AFM), Fourier transform infrared spectroscopy (FT-IR), Raman
spectroscopy, X-ray diffraction (XRD), thermogravimetric analysis (TGA), and acid-base
titration. Multi SO3H supported on reduced graphene oxide nanosheets was found to be an
efficient catalyst for green synthesis of 6,6′-(aryl(alkyl)methylene)bis(2,4-dialkylphenol)
Derivatives from 2,4-dialkylphenols and aromatic and aliphatic aldehydes in aqueous media
under microwave irradiation. The synthesis of 6,6′-(aryl(alkyl)methylene)bis(2,4-dialkylphenol)
Derivatives were carried out in the presence of catalytic amount of the RGO-SO3H, under
thermal and microwave conditions to afford the desired products in high and excellent yields
respectively. In addition, the catalyst could be recovered easily and reused several times without
any considerable loss of its catalytic activity.
Keywords: Graphene; antioxidants; green Synthesis; microwave; heterogeneous catalyst
1

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Introduction
The phenolic compounds, especially polyphenols have become an intense focus of research
interest because of their perceived health-beneficial effects, such as anti-carcinogenic, anti-
atherogenic, anti-inflammatory, and anti-microbial activities.1-3 The phenol structural unit is
an important component in many natural products, pharmaceuticals, catalysts and advanced
5
materials.4,
The hydroxyl groups in these materials are responsible for their
specific activity.6-8 Some important and biologically active phenol-based compounds (Figure 1) 9,
10
act as efficient free radicals scavengers by donating their alcoholic hydrogen or one of their
delocalized electrons. These compounds are employed in the food industry, in propellant and
explosive materials and in other areas as effective antioxidants.
Figure 1. Examples of biologically, and antioxidantly active compounds based phenol.
Owing to the wide application and significance of bisphenolic antioxidants, there is considerable
interest in the synthesis of these compounds catalyzed by different homogeneous and
heterogeneous catalysts.11-24 Although each of these protocols has its advantages some of them
often suffer from one or more disadvantages. Low yields, long reaction times, tedious work-up
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processes, use of hazardous organic solvent, and non-reusable catalytic system are most
important deficiencies associated with these methods.
Acid catalyzed chemical processes are widely employed in the organic synthesis to produce
different chemicals.25 In terms of green chemistry, it is very important to replace liquid acid
catalysts such as HF, HCl, and H2SO4 with solid acid catalysts in organic synthesis.26-28
Graphene is one of typical support for preparation of heterogeneous catalysts. Graphene
possesses a large specific surface area, open porous structure, flexibility, chemical and thermal
stability, non-toxicity, wet ability, and very high electrical conductivity, which warrant it as a
good candidate support for preparation of heterogeneous catalysts.29-34 Also, graphene oxide and
reduced graphene oxide were employed in the area of scientific works such as sensors,35, 36
supercapacitors,37 and photocatalyst.38, 39
In last two decades, several reactions have been occurred in the presence of solid catalysts for
potential application of microwave irradiation in organic synthesis.40, 41 In contrast microwave
irradiation when a conventional thermal method was employed, catalytic activity of solid
heterogeneous catalyst is low.40 Since the materials and catalyst are directly heated under
microwave irradiation without the need for heat transfer, the reaction time is remarkably
shortened. Consequently, alternative heating and strict temperature control of a catalyst are some
of the features of the reaction catalyzed by a solid catalyst when exposed to microwave
irradiation.
Due to the importance of the described compounds, and in continuation of our previous study on
preparation of heterogeneous catalytic systems and microwave irradiation,42-50 herein, we hope
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to present the RGO-SO3H as a heterogeneous catalyst for the preparation of 6,6′-
(aryl(alkyl)methylene)bis(2,4-dialkylphenol) antioxidants in water under microwave irradiation.
Experimental Section
Materials and apparatus
The chemical and materials used in this research were purchased from Merck chemical company
and used without purification. The IR spectra were obtained as KBr pellets in the range of 400-
1
13
4000 cm-1 on a Perkin-Elmer 781 spectrophotometer. The H NMR and C NMR spectra were
recorded in dimethyl sulfoxide (DMSO)-(d6) solvent on a Brucker DRX-400 MHz spectrometer
using tetramethylsilane (TMS) as an internal standard. The crystallographic structure of prepared
catalyst was investigated on a Philips instrument with 1.54 Å wavelengths of X-ray beam and Cu
anode material, at a scanning speed of 2° min-1 from 10° to 80° (2θ). The elemental analyses (C,
H, N) were obtained from a Carlo ERBA Model EA 1108 analyzer. The Microwave conditions
were carried out in microwave oven specially designed for organic synthesis (Milestone LAVIS
Basic Microwave). Thermogravimetric analysis (TGA) was performed on a mettler TA4000
system TG-50 at a heating rate of 10 K min-1 under N2 atmosphere. The Raman spectra were
recorded with an Almega Thermo Nicolet Dispersive Raman spectrometer excited at 532 nm.
The morphology of the catalyst was characterized by FESEM Hitachi S4160 instrument. The
TEM images were recorded by a Zeiss-EM10C with an acceleration voltage of 80 kV. The AFM
image of GO nanosheets and RGO-SO3H were measured using a scanning probe microscope
(SPM-9600, Shimadzu). Melting points was obtained with a Yanagimoto micro melting point
apparatus and are uncorrected. The purity determination of the substrates and reaction
monitoring were accomplished by TLC on silica-gel polygram SILG/UV 254 plates (from
Merck Company).
4

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Preparation of graphene oxide nanosheets
The GO nanosheets were prepared from natural graphite by the modified Hummer’s method.51
Typically, 5.0 g of natural graphite powder and 2.5 g of sodium nitrate were mixed with 115 mL
of sulfuric acid (98%) in a 1000 mL round-bottom flask equipped with a magnetic stirrer and
condenser place in an ice bath. The obtained solution was stirred and slowly added 15.0 g of
potassium permangenate, and the stirring was continued for 2 h. The mixture solution was
o
transferred to a water bath (35 C) and stirred for 30 min. After this step, 230 mL of deionized
water was slowly added into the solution and the solution temperature monitored was about 98
°C and stirred for 15 min. Then, 700 mL of deionized water and 50 mL of H2O2 (30%) were
sequentially added to the mixture solution to terminate the reaction. The resulting materials was
filtered and washed with 5% HCl solution followed by distilled water for several times. The
solution was filtered under reduced pressure by vacuum pump over sinter-glass (G4). After
drying in vacuum at 60 °C for 12 h, the graphite oxide powder was obtained. The graphite oxide
was dispersed in distilled water to make concentration of 0.5 mg mL-1, and exfoliated by
ultrasound (45 w) for 30 min to generate GO nanosheets, followed by centrifugation at 3500 rpm
for 30 min to remove un-exfoliated graphite oxide.
Preparation of reduced graphene oxide nanosheets
First, reduced graphene oxide (RGO) was synthesized by the chemical reduction of GO using
NaBH4 as a reducing agent. In a 1000 mL round-bottom flask, 1.0 g of the GO dispersion was
added into deionized water (700 mL), followed by sonication (40 w) for 15 min. Then, 2.4 g of
NaBH4 was added into the round-bottom flask, heating at 100 °C for 24 h. After this step, the
resulted product was washed with water several times and filtered under reduced pressure by
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vacuum pump over sinter glass (G4) and centrifugation at 3500 rpm for 15 min to obtain RGO
nanosheets.
Preparation of sulfonated reduced graphene oxide nanosheets
The RGO-SO3H was prepared from the hydrothermal sulfonation of RGO using H2SO4 (100 %)
at 180 °C. 1.0 g of RGO was added into 50 mL of H2SO4. After sonication (40 w) for 15 min, the
mixture was transferred into a round-bottom flask under nitrogen atmosphere and stirring to heat
at 180 °C for 24 h. Then, the prepared catalyst was washed with a large amount of deionized
water and drying at 80 °C for 12 h. Finally RGO-SO3H was obtained and employed in the
synthesis of bisphenolic antioxidants.
Procedure for pH analysis of prepared catalyst
The density of sulfonated group on RGO, and GO was calculated by back acid-base titration and
aqueous solution of NaCl. First, 100 mg of RGO-SO3H was sonicated in a water bath for 10 min
under nitrogen atmosphere to degas CO2. Next 10 mL of NaOH 0.098 N was added and the
mixture stirred for 2 h at room temperature. Subsequently, the mixture was filtered through
sintered glass (G-4) and washed several times with deionized water. The filtrate was then titrated
with HCl 0.1 N until reaching the neutral point as monitored by phenolphthalein as indicator.
The volume required to reach the neutral point was substracted from the initial volume of NaOH
used to obtain the volume of NaOH which has reacted with sulfonated group on RGO. In
addition, by the solution of NaCl, the total density of sulfonated groups was measured. To an
aqueous solution of NaCl (1 M, 25 mL) with the primary pH 6.11, the catalyst (100 mg) was
added, and the resulting mixture was stirred for 4 h. Then, pH of the solution was measured.
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General procedure for the preparation of bisphenolic antioxidants catalyzed by RGO-SO3H
under thermal conditions
In a 25 mL round-bottom flask equipped with a magnetic bar and condenser, a mixture of 2,4-
dialkylphenol (6 mmol), aromatic and aliphatic aldehyde (2 mmol) and RGO-SO3H (40 mg) was
heated at 100 °C under solvent free conditions for appropriate time according to Table 2. The
progress of the reaction was monitored by thin layer chromatography (TLC) (n-hexane: ethyl
acetate 10:4). At the end of the reaction, the mixture was cooled to the room temperature and 15
mL of acetone (3×5 mL) was added. The RGO-SO3H was filtered under reduced pressure using
vacuum pump over sinter glass (G4). The solution was recovered by evaporation on a rotary
evaporator. After that, the solid materials were washed with n-hexane (5 mL) and deionized
water, successively, to afford the pure products. The desired products were kept in an oven at 80
°C for 12 h.
General procedure for the preparation of bisphenolic antioxidants catalyzed by RGO-SO3H
under microwave irradiation
A mixture of 2,4-dialkylphenol (6 mmol), aromatic and aliphatic aldehyde (2 mmol), RGO-
SO3H (30 mg), and water (5 mL) as a green solvent in an open tall beaker was irradiated inside
microwave oven at 300 W for the appropriate time. The progress of the reaction was monitored
by TLC (n-hexane: ethyl acetate 10:4). After completion of the reaction, the mixture was cooled
to room temperature and 20 mL of acetone (4×5 mL) was added. The RGO-SO3H was filtered
under reduced pressure using vacuum pump over sinter glass (G4). The solution was recovered
by evaporation on a rotary evaporator. After that, the solid materials were washed with n-hexane
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(5 mL) and deionized water, successively, to afford the pure products. The desired products were
kept in an oven at 80 °C for 12 h.
Procedure for recovery and reusability of the catalyst
Reusability of the RGO-SO3H was studied in the reaction of 2,4-dimethylphenol and 4-
bromobenzaldehyde. At the end of each cycle, the catalyst was separated by filtration, washed
°
exhaustively with deionized water, n-hexane, and ethanol, then dried at 100 C for 12 h before
being used with fresh 2,4-dimethylphenol and 4-bromobenzaldehyde. The catalyst can be reused
seven cycles under microwave irradiation without any reduction in its catalytic activity.
Spectroscopic and physical data
6,6′-((4-nitrophenyl)methylene)bis(2,4-dimethylphenol) (Table 2, Compound 3a): mp: 136-
1
138 °C; IR (KBr): ν (cm-1) 3482, 3249, 2958, 1599, 1522, 1475, 1349, 1292, 1113, 879. H
NMR (400 MHz, DMSO-d6/TMS) δ(ppm): 1.95 (6H, s, Me), 2.47 (6H, s, Me), 6.22 (1H, s,
Ar3CH), 6.26 (2H, s, OH), 6.75 (2H, s, 3-H DMP), 7.21 (2H, d, J=8 Hz, 2,6-H aldehyde), 8.09
(2H, s, 5-H DMP), 8.11 (2H, d, J=8 Hz, 3,5-H aldehyde). Anal. Calcd for C23H23NO4: C, 73.19;
H, 6.14; N, 3.71%. Found: C, 73.06; H, 6.12; N, 3.70%.
6,6′-((3-nitrophenyl)methylene)bis(2,4-dimethylphenol) (Table 2, Compound 3b): mp: 141-
1
143 °C; IR (KBr): ν (cm-1) 3433, 3082, 2916, 1606, 1525, 1481, 1347, 1217, 1096, 861. H
NMR (400 MHz, DMSO-d6/TMS) δ(ppm): 1.91 (6H, s,Me), 2.46 (6H, s, Me), 6.24 (1H, s,
Ar3CH), 6.28 (2H, s, OH), 6.57 (2H, s, 3-H DMP), 6.75 (1H, d, J=7.8 Hz, 5-H aldehyde), 7.43
(1H, d, 6-H aldehyde), 7.53 (2H, d, J=7.8 Hz, 2,4-H aldehyde), 7.73 (2H, s, 5-H DMP). Anal.
Calcd for C23H23NO4: C, 73.19; H, 6.14; N, 3.71%. Found: C, 73.21; H, 7.05; N, 3.67%.
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6,6′-((4-chlorophenyl)methylene)bis(2,4-dimethylphenol) (Table 2, Compound 3c): mp: 158-
160 °C; IR (KBr): ν (cm-1) 3498, 3467, 3018, 2918, 1587, 1472, 1381, 1254, 1183, 1048, 862.
1H NMR (400 MHz, DMSO-d6/TMS) δ(ppm): 2.03 (6H, s, Me), 2.08 (6H, s, Me), 6.10 (1H, s,
Ar3CH), 6.26 (2H, s, OH), 6.71 (2H, s, 3-H DMP), 6.96 (2H, d, J=7.9 Hz, 2,6-H aldehyde), 7.28
(2H, s, 5-H DMP), 7.97 (2H, d, J=7.9 Hz, 3,5-H aldehyde). Anal. Calcd for C23H23ClO2: C,
75.30; H, 6.32%. Found: C, 75.19; H, 6.29%.
6,6′-((2-chlorophenyl)methylene)bis(2,4-dimethylphenol) (Table 2, Compound 3d): mp: 191-
1
193 °C; IR (KBr): ν (cm-1) 3482, 2918, 1600, 1598, 1474, 1331, 1291, 1190, 1037, 866. H
NMR (400 MHz, DMSO-d6/TMS) δ(ppm): 1.93 (6H, s, Me), 2.08 (6H, s, Me), 6.19 (2H, s, OH),
6.40 (1H, s, Ar3CH), 6.71 (2H, s, 3-H DMP), 6.83 (1H, t, J=8 Hz, 4-H aldehyde), 7.18 (2H, s, 5-
H DMP), 7.35 (1H, d, J=7.7 Hz, 6-H aldehyde), 7.96 (2H, d, 3,5-H aldehyde). Anal. Calcd for
C23H23ClO2: C, 75.30; H, 6.32%. Found: C, 75.29; H, 6.34%.
6,6′-((2,4-dichlorophenyl)methylene)bis(2,4-dimethylphenol) (Table 2, Compound 3e): mp:
183-185 °C; IR (KBr): ν (cm-1) 3500, 3466, 3022, 2917, 1602, 1481, 1405, 1252, 1184, 1138,
847. 1H NMR (400 MHz, DMSO-d6/TMS) δ(ppm): 1.92 (6H, s, Me), 2.08 (6H, s, Me), 6.17 (2H,
s, OH), 6.33 (1H, s, Ar3CH), 6.73 (2H, s, 3-H DMP), 7.80 (2H, s, 5-H DMP), 7.29 (1H, d, J=8
Hz, 6-H aldehyde), 7.50 (1H, d, J=8 Hz, 5-H aldehyde), 8.01 (1H, s, 2H aldehyde). Anal. Calcd
for C23H22Cl2O2: C, 68.83; H, 5.53%. Found: C, 68.64; H, 5.49%.
6,6′-((2-fluorophenyl)methylene)bis(2,4-dimethylphenol) (Table 2, Compound 3f): mp: 146-
1
148 °C; IR (KBr): ν (cm-1) 3484, 3920, 1584, 1482, 1333, 1290, 1223, 1193, 1140, 866. H
NMR (400 MHz, DMSO-d6/TMS) δ(ppm): 1.95 (6H, s, Me), 2.09 (6H, s, Me), 6.26 (2H, s, OH),
6.35 (1H, s, Ar3CH), 6.72 (2H, s, 3-H DMP), 6.72 (1H, t, J=7.8 Hz, 4-H aldehyde), 7.06 (2H, s,
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13
5-H DMP), 7.20 (1H, d, J=8 Hz, 6-H aldehyde), 7.98 (2H, d, t, 3,5-H aldehyde). C NMR (100
MHz, DMSO-d6/TMS) δ(ppm): 17.18, 20.95, 36.84, 115.28, 115.50, 124.44, 127.42, 128.15,
129.80, 130.88, 131.98, 132.13, 150.64, 159.51, and 161.94. Anal. Calcd for C23H23FO2: C,
78.83; H, 6.62%. Found: C, 78.72; H, 6.61%.
6,6′-((3-fluorophenyl)methylene)bis(2,4-dimethylphenol) (Table 2, Compound 3g): mp: 94-96
1
°C; IR (KBr): ν (cm-1) 3335, 3923, 1611, 1586, 1482, 1442, 1385, 1292, 1189, 1142, 783. H
NMR (400 MHz, DMSO-d6/TMS) δ(ppm): 1.95 (6H, s, Me), 2.09 (6H, s, Me), 6.14 (1H, s,
Ar3CH), 6.28 (2H, s, OH), 6.66 (2H, s, 3-H DMP), 6.72 (2H, d, J=7.9 Hz, 5,6-H aldehyde), 6.96
(1H, d, J=7.9 Hz, 2-H aldehyde), 7.25 (1H, d, J=7.9 Hz, 4-H aldehyde), 8.00 (2H, s, 5-H DMP).
Anal. Calcd for C23H23FO2: C, 78.83; H, 6.62%. Found: C, 78.79; H, 6.54%.
6,6′-((4-bromophenyl)methylene)bis(2,4-dimethylphenol) (Table 2, Compound 3h): mp: >240
1
°C; IR (KBr): ν (cm-1) 3468, 2917, 1601, 1480, 1401, 1251, 1184, 1138, 1072, 860. H NMR
(400 MHz, DMSO-d6/TMS) δ(ppm): 2.06 (6H, s, Me), 2.08 (6H, s, Me), 6.07 (1H, s, Ar3CH),
6.25 (2H, s, OH), 6.70 (2H, s, 3-H DMP), 6.88 (2H, d, J=7.9 Hz, 2,6-H aldehyde), 7.38 (2H, s,
5-H DMP), 7.96 (2H, d, J=7.9 Hz, 3,5-H aldehyde). Anal. Calcd for C23H23BrO2: C, 67.16; H,
5.64%. Found: C, 67.18; H, 5.61%.
6,6′-((3-bromophenyl)methylene)bis(2,4-dimethylphenol) (Table 2, Compound 3i): mp: 124-
126 °C; IR (KBr): ν (cm-1) 3345, 2922, 1591, 1478, 1383, 1325, 1293, 1188, 1143, 1075, 863.
1H NMR (400 MHz, DMSO-d6/TMS) δ(ppm): 2.03 (6H, s, Me), 2.08 (6H, s, Me), 6.10 (1H, s,
Ar3CH), 6.26 (2H, s, OH), 6.72 (2H, s, 3-H DMP), 6.96 (1H, d, J=8 Hz, 6-H aldehyde), 7.19
(1H, d, J=8 Hz, 5-H aldehyde), 7.21 (1H, J=7.8 Hz, 4-H aldehyde), 7.33 (1H, J=7.8 Hz,2-H
aldehyde), 8.01 (2H, s, 5-H DMP). 13C NMR (100 MHz, DMSO-d6/TMS) δ(ppm): 17.19, 20.94,
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43.50, 121.84, 124.65, 127.57, 128.07, 128.73, 128.98, 129.86, 130.57, 130.94, 131.98, 148.06,
and 150.68. Anal. Calcd for C23H23BrO2: C, 67.16; H, 5.64%. Found: C, 67.08; H, 5.51%.
6,6′-((2-bromophenyl)methylene)bis(2,4-dimethylphenol) (Table 2, Compound 3j): mp: 188-
190 °C; IR (KBr): ν (cm-1) 3484, 2917, 1597, 1566, 1474, 1330, 1189, 1140, 1023, 866, 750. 1H
NMR (400 MHz, DMSO-d6/TMS) δ(ppm): 1.94 (6H, s, Me), 2.09 (6H, s, Me), 6.18 (2H, s, OH),
6.35 (1H, s, Ar3CH), 6.72 (2H, s, 3-H DMP), 6.83 (1H, d, J=8 Hz, 6-H aldehyde), 7.08 (1H, d,
J=8 Hz, 4-H aldehyde), 7.21 (1H, d, J=7.7Hz, 3-H aldehyde), 7.53 (1H, t, J=7.7Hz, 5-H
aldehyde), 7.97 (2H, s, 5-H DMP). Anal. Calcd for C23H23BrO2: C, 67.16; H, 5.64%. Found: C,
67.20; H, 5.59%.
6,6′-((phenyl)methylene)bis(2,4-dimethylphenol) (Table 2, Compound 3k): mp: 113-115 °C;
1
IR (KBr): ν (cm-1) 3339, 3021, 2920, 1600, 1481, 1447, 1384, 1292, 1186, 1142, 864, 702. H
NMR (400 MHz, DMSO-d6/TMS) δ(ppm): 2.06 (6H, s, Me), 2.08 (6H, s, Me), 6.13 (1H, s,
Ar3CH), 6.29 (2H, s, OH), 6.70 (2H, s, 3-H DMP), 6.97 (2H, t, J=8 Hz, 3,5-H aldehyde), 7.11
(1H, t, J=8 Hz, 4-H aldehyde), 7.23 (2H, d, J=8 Hz, 2,6-H aldehyde), 7.93 (2H, s, 5-H DMP).
Anal. Calcd for C23H24O2: C, 83.10; H, 7.28%. Found: C, 83.14; H, 7.24%.
6,6′-((4-methylphenyl)methylene)bis(2,4-dimethylphenol) (Table 2, Compound 3l): mp: 168-
170 °C; IR (KBr): ν (cm-1) 3501, 2917, 1604, 1476, 1330, 1188, 1139, 1031, 866. 1H NMR (400
MHz, DMSO-d6/TMS) δ(ppm): 2.01 (6H, s, Me), 2.07 (6H, s, Me), 2.21 (3H, s, CH3-aldehyde),
6.06 (1H, s, Ar3CH), 6.28 (2H, s, OH), 6.68 (2H, s, 3-H DMP), 6.84 (2H, d, J=8.1 Hz, 3,5-H
aldehyde), 7.01 (2H, s, 5-H DMP), 7.88 (2H, d, J=8.1 Hz, 2,6-H aldehyde). 13C NMR (100 MHz,
DMSO-d6/TMS) δ(ppm): 17.21, 20.97, 43.26, 124.38, 127.30, 128.18, 128.94, 129.45, 129.58,
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131.95, 134.81, 141.78, and 150.69. Anal. Calcd for C24H26O2: C, 83.20; H, 7.56%. Found: C,
83.14; H, 7.49%.
6,6′-((3-methoxyphenyl)methylene)bis(2,4-dimethylphenol) (Table 2, Compound 3m): mp:
1
>270 °C; IR (KBr): ν (cm-1) 3453, 2975, 1622, 1505, 1402, 1347, 1230, 1088, 790. H NMR
(400 MHz, DMSO-d6/TMS) δ(ppm): 1.94 (6H, s, Me), 2.08 (6H, s, Me), 3.80 (3H, s, OCH3),
6.14 (1H, s, Ar3CH), 6.28 (2H, s, OH), 6.68 (2H, s, 3-H DMP), 6.84 (1H, s, 2-H aldehyde), 6.94
(1H, d, J=7.9 Hz, 4-H aldehyde), 7.64 (2H, s, 5-H DMP), 8.12 (2H, m, 5,6-H aldehyde). Anal.
Calcd for C24H26O3: C, 79.53; H, 7.23%. Found: C, 79.58; H, 7.20%.
6,6′,6″,6′′′-(1,4-phenylenebis(methanetriyl))tetrakis(2,4-dimethylphenol)
(Table
2,
Compound 3n): mp: 65-67 °C; IR (KBr): ν (cm-1) 3429, 3012, 2918, 1686, 1602, 1479, 1294,
1208, 1016, 861. 1H NMR (400 MHz, DMSO-d6/TMS) δ(ppm): 1.90 (12H, s, Me), 2.10 (12H, s,
Me), 6.07 (2H, s, Ar3CH), 6.25 (4H, s, OH), 6.52 (2H, s, 3-H DMP), 6.61 (4H, m, 2,6-H
aldehyde), 6.72 (4H, s, 5-H DMP), 7.77 (2H, m, 3,5-H aldehyde), 7.94 (2H, m, 3,5-H aldehyde).
13C NMR (100 MHz, DMSO-d6/TMS) δ(ppm): 16.41, 17.20, 20.56, 20.95, 43.28, 114.88,
123.88, 124.32, 124.68, 127.30, 127.61, 128.29, 129.19, 129.81, 130.28, 131.58, 132.02, 141.99,
150.66, and 153.50. Anal. Calcd for C40H42O4: C, 81.88; H, 7.21%. Found: C, 81.82; H, 7.20%.
6,6′-((4-nitrophenyl)methylene)bis(2,4-di-tert-butylphenol) (Table 2, Compound 3o): mp:
153-155 °C; IR (KBr): ν (cm-1) 3491, 2959, 1690, 1598, 1522, 1474, 1417, 1350, 1188, 116,
1
862. H NMR (400 MHz, DMSO-d6/TMS) δ(ppm): 1.05 (18H, s, tert-butyl), 1.33 (18H, s, tert-
butyl), 6.28 (1H, s, Ar3CH), 6.47 (2H, s, OH), 7.13 (2H, s, 3-H DMP), 7.13 (2H, d, J=8 Hz, 2,6-
H aldehyde), 7.70 (2H, s, 5-H DMP), 8.13 (2H, d, J=8 Hz, 3,5-H aldehyde). 13C NMR (100
MHz, DMSO-d6/TMS) δ(ppm): 30.35, 31.70, 34.27, 35.16, 44.12, 121.76, 123.47, 125.08,
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130.50, 130.64, 137.52, 141.46, 146.18, 151.02, and 153.25. Anal. Calcd for C35H47NO4: C,
77.03; H, 8.68; N, 2.57%. Found: C, 77.07; H, 8.61; N, 2. 59%.
6,6′-((3-nitrophenyl)methylene)bis(2,4-di-tert-butylphenol) (Table 2, Compound 3p): mp:
1
118-120 °C; IR (KBr): ν (cm-1) 3528, 2959, 1530, 1473, 1350, 1186, 1023, 884. H NMR (400
MHz, DMSO-d6/TMS) δ(ppm): 2.01 (6H, s, Me), 2.06 (6H, s, Me), 6.06 (1H, s, Ar3CH), 6.29
(2H, s, OH), 6.93 (2H, s, 3-H DMP), 7.16 (1H, d, J=8 Hz, 6-H aldehyde), 7.55 (2H, m, 4,5-H
aldehyde), 7.64 (2H, s, 5-H DMP), 8.12 (1H, s, 2-H aldehyde). Anal. Calcd for C35H47NO4: C,
77.03; H, 8.68; N, 2.57%. Found: C, 76.97; H, 8.64; N, 2. 55%.
6,6′-methylenebis(2,4-dimethylphenol) (Table 2, Compound 3q): mp: 105-107 °C; IR (KBr): ν
(cm-1) 3424, 3299, 2917, 1609, 1482, 1381, 1286, 1193, 1150, 855. 1H NMR (400 MHz, DMSO-
d6/TMS) δ(ppm): 2.00 (6H, s, Me), 2.10 (6H, s, Me), 3.74 (2H, s, CH2), 6.62 (2H, s, OH), 6.68
(2H, s, 3-H DMP), 8.25 (2H, s, 5-H DMP). Anal. Calcd for C17H20O2: C, 79.65; H, 7.86%.
Found: C, 79.62; H, 7.79%.
6,6′-((2-methylpropyl)methylene)bis(2,4-dimethylphenol) (Table 2, Compound 3t): mp: 160-
163 °C; IR (KBr): ν (cm-1) 3380, 3300, 2951, 2916, 1604, 1480, 1367, 1226, 1184, 1020, 858,
617. 1H NMR (400 MHz, DMSO-d6/TMS) δ(ppm): 0.84 (6H, d, J=7.8 Hz, 2(Me)CH), 1.34 (1H,
m, 2(Me)CH), 1.78 (2H, t, J=7.8 Hz, CH2), 2.09 (6H, s, Me), 4.60 (1H, t, J=7.8 Hz, Ar3CH),
6.65 (2H, s, OH), 6.81 (2H, s, 3-H DMP), 8.25 (2H, s, 5-H DMP). Anal. Calcd for C21H28O2: C,
80.73; H, 9.03%. Found: C, 80.69; H, 8.99%.
6,6′-((n-butyl)methylene)bis(2,4-dimethylphenol) (Table 2, Compound 3u): mp: 140-143 °C;
1
IR (KBr): ν (cm-1) 3477, 3295, 2951, 2919, 1479, 1288, 1154, 1019, 857. H NMR (400 MHz,
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DMSO-d6/TMS) δ(ppm): 0.80 (3H, m, CH3-aldehyde), 1.13 (2H, m, CH2-aldehyde), 1.25 (2H,
m, CH2-aldehyde), 1.88 (2H, m, CH2-aldehyde), 2.08 (6H, s, Me), 4.49 (1H, t, J=7.8 Hz,
Ar3CH), 6.65 (2H, s, OH), 6.79 (2H, s, 3-H DMP), 8.20 (2H, s, 5-H DMP). Anal. Calcd for
C21H28O2: C, 80.73; H, 9.03%. Found: C, 80.76; H, 9.09%.
Results and Discussion
The importance of antioxidants in preventive medicine, food chemistry, and propellants are
recognized since several years. Due to the significance of the described compounds, our plan of
constructing 6,6′-(aryl(alkyl)methylene)bis(2,4-dialkylphenol) antioxidants has been done
through one-pot and pseudo-three-component reaction from 2,4-dialkylphenol and various
aromatic and aliphatic aldehydes under microwave irradiation in water (Scheme 1).
Scheme 1. Synthesis of bisphenolic antioxidants.
Preparation of catalyst
To prove our plan, it was prepared the RGO-SO3H as outlined in Scheme 2 according the
previously reported by Xiao et al. with a few modification.52 First natural graphite which is
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commercially available was converted to graphite oxide using sodium nitrate, H2SO4, and
potassium permangenante.51 This step introduced oxygen containing groups for example epoxy,
hydroxyl, and carboxylic acid groups on the surface of graphite. After that, the graphite oxide
was sonicated (45 w) for 15 min to produce GO nanosheets. For preparation of RGO-SO3H, the
prepared RGO using NaBH4 as reducing agent was treated with H2SO4 (100 %) to afford RGO-
SO3H. The RGO-SO3H was employed in synthesis of 6,6′-(aryl(alkyl)methylene)bis(2,4-
dialkylphenol) antioxidants in water under microwave irradiation.
O
O
OH
HO
OH
OH
NaBH4
)))))
Hummer's method
Graphite
Graphite oxide
GO nanosheets
O
O
O
O
S
H2SO4
180 0C
HO
S
OH
RGO nanosheets
RGO-SO3H
Scheme 2. Synthetic route for preparation of catalyst.
Characterization of RGO-SO3H
After successful preparation of the RGO-SO3H, the catalyst was characterized by some
microscopic and spectroscopic techniques including FESEM, TEM, AFM, FT-IR and Raman
spectroscopy, XRD, TGA, and back acid-base titration.
To investigate the morphology of the prepared catalyst, FESEM images were taken for the GO,
and RGO-SO3H. The transparent and flake-like sheets of the prepared GO nanosheets are
observed in Figure 2a. Figure 2a was found that GO nanosheets consists of randomly aggregated
and crumpled thin sheets which also observed with wrinkles and folds on the surface of GO
nanosheets. This result confirmed that two dimensional GO nanosheets can be produced from
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exfoliation of suspended graphite oxide. The Figure 2b revealed that the presence of functional
groups on the surface of GO are carried out, which is quite different morphology from the
pristine GO nanosheets. Figures 2c and 2d exhibit the TEM images of GO and RGO nanosheets
respectively. In these images, it seems that the GO and RGO exhibit a typical exfoliated and two-
dimensional nanosheets with a rather and large flat and smooth flake-like morphology with
several layers. In addition, they reveal that two-dimensional flake-like of pristine graphite is still
in GO and RGO nanosheets after Hummer’s method.
Figure 2. FESEM images of a) GO nanosheets b) RGO-SO3H and TEM images of c) GO
nanosheets d) RGO.
As shown in Figure 3a, the AFM analysis reveals that the measured values of thickness are in the
range 0.9-1.5 nm, indicating that exfoliated mono- and di-layer graphene oxide was obtained in
this study. These GO layers should be mostly mono-layered, although these amount are
somewhat larger than the interlayer spacing (0.78 nm) of the parent GO. The sheets are a little
more ‘bumpy’ than predicted, which is possibly due to the existence of abundant functional
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groups, such as carboxylic, epoxy, and hydroxyl groups, bonded to both sides of the GO sheets,
which disrupts the original conjugation and introduces lattice defects to result in folds and
distortions on the sheets. After reduction of GO with NaBH4, the process of sulfonation was
done and the AFM analysis of the RGO-SO3H was provided (Figure 3b). As shown in this
Figure, the measured values of thickness in RGO-SO3H was increased and the range of 2.4-4.1
nm indicating that the process of functionalization was successfully occurred and the functional
groups were immobilized on the surface of RGO. According to the hydrogen bonding between
the layers of RGO-SO3H, the prepared catalyst was three to seven layers of graphene sheets.
Figure 3. AFM images of a) GO nanosheets b) RGO-SO3H
Figure 4a-d shows the FT-IR spectra of graphite, GO, RGO, and RGO-SO3H respectively. The
high symmetry introduced to pristine graphite generates very weak infrared peaks due to the
weak difference of charge states and very small induced electric dipole. The peak related to
carbon-carbon double bonds at 1573 cm-1 is not sharp in the spectrum of graphite (Figure 4a).
The FT-IR spectrum of GO was shown in Figure 4b.The process of Hummer’s method and
sonication process breaks the symmetry of graphite. The peak at approximately 1580 cm-1 is
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attributed to carbon-carbon double bonds. This peak is sharper than graphite due to the un-
symmetry of GO. Also, this spectrum shows the peaks at 1064, 1719, and 3394 cm-1 which could
be assigned to carbon-oxygen, carbonyl, and hydroxyl stretching mode of functional groups such
as hydroxyl, carboxylic, and epoxy groups attachment to GO respectively. The chemical
reduction of GO with NaBH4 produce RGO that the FT-IR spectrum of RGO is shown in Figure
4c. This spectrum shows that the peaks of the hydroxyl and carbonyl groups were disappeared
due to the used NaBH4 as reducing agent. The peak at 3423 cm-1 is related to presence of water
on KBr pellets. Also, the presence of the peak at 1566 cm-1 show that after chemical reduction at
100 °C for 24 h, the RGO is still flake-like sheets. At the end of this image, Figure 4d shows FT-
IR spectrum of RGO-SO3H. H2SO4 treatment also results in the appearance of the peaks at about
1384 and 1215 cm-1, which corresponds to the SO2 symmetric and asymmetric stretching modes
respectively. In addition, in the low frequency part of spectrum the line at 605 cm-1 was assigned
to carbon-sulfur stretching mode, suggesting the existence of covalent sulfonic acid groups on
the surface of GO nanosheets.
Figure 4. FT-IR spectra of a) graphite b) GO c) RGO d) RGO-SO3H.
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Figure 5a-d shows XRD patterns of graphite, GO, RGO, and G-SO3H respectively. The XRD
pattern of graphite (Figure 5a) shows a diffraction peak at approximately 2θ= 26.5°
corresponding to the interlayer spacing (d-spacing). After to do Hummer’s method, the peak at
about 2θ= 26.5° was broad peak and the peak at 2θ= 12° was appeared. The interlayer spacing
(d-spacing) of GO was calculated 0.78 nm which revealed the introduction of oxygen species on
graphene network sheets (Figure 5b).53 After chemical reduction of exfoliated GO with NaBH4,
the diffraction peak of GO at 2θ= 12° disappeared and a broad peak at about 2θ= 24° was
observed, indicating the fully reduction and exfoliation of GO and the production of RGO
nanosheets.54 As shown in Figure 5c in the RGO nanosheets was rather broad peak and
significantly different from that observed for graphite (2θ= 26.5°). Figure 4d shows XRD pattern
of RGO-SO3H after hydrothermal sulfonation. The XRD pattern (Figure 5d) has very similar
peaks to RGO suggesting their similar graphene layers.
Figure 5. XRD pattern of a) graphite b) GO c) RGO d) RGO-SO3H.
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Raman spectroscopy is strongly sensitive to the structure of graphene and it has proved to be an
essential tool to characterize graphene. Typical Raman spectrum of GO nanosheet is shown in
Figure 6. The D-band is related to disorder induced scattering resulting from imperfection of
disorder graphene. The G-band is associated with an E2g mode of graphite and is related to
vibration of sp2 bonded carbon hybridize in a two dimensional graphite. The D band appears at
about 1347 cm-1, and the G band appears at approximately 1593 cm-1. The G-band arises from
the stretching of the carbon-carbon bond in graphitic materials, and is related to sp2 carbon
systems. The D-band is caused by disordered structure of graphene. The other Raman bands are
at 2717 cm-1 (2D band), and 2931 cm-1 (D+G-band).55
Figure 6. Raman spectrum of GO.
TGA analysis curves of GO and RGO-SO3H are compared in Figure 7. Both curves show similar
characteristics. As shown in Figure 7a, the weight loss (8%) before 160 °C is caused by the
release of trapped water between GO nanosheets.56 The weight loss (23%) between 160 °C and
260 °C is attributed to the decomposition of less stable functional groups for example hydroxyl,
carboxylic acid, and epoxy on the surface of GO nanosheets.57 The presence of sulfonated groups
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on RGO nanosheets were further analyzed by TGA (Figure 7b). A little weight loss (8%) before
176 °C is attributed to the trapped water. For the prepared catalyst, there is a slow decrease of
weight (46%) when the temperature is between 400 °C and 580 °C that is attributed to sulfonated
groups. Thermogravimetric analysis can estimate account of functional groups per carbon
atoms.58 To calculate the extent of functionalization, weight loss values were employed together
with the molecular weight of the different groups and the following equation was applied.
Where X stands for the number of carbon atoms in RGO-SO3H per each covalent functional
group, R (%) is the residual mass at 580 °C in the TGA plot, L (%) is the weight loss in the range
of 176°C and 580 °C, and Mw is the molecular weight of the sulfonated groups. In according to
the above equation, taking in to account that the sulfonated groups measurement indicated that
one functionality every approximately thirty four carbon atoms.
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Figure 7. Thermogravimetric analysis of a) GO b) RGO-SO3H.
The density of SO3H groups on the RGO was determined by back acid-base titration and solution
of NaCl. The back acid-base titration showed that the amount of SO3H attached to RGO is 2.15
mmol. g-1. Also, the solution of NaCl determined the amount of sulfonated groups is 2.15 mmol.
g-1.
Catalytic evaluation of RGO-SO3H in the synthesis of bisphenolic antioxidants under
microwave irradiation
The prepared RGO-SO3H was used as heterogeneous catalysts in the synthesis of 6,6′-
(aryl(alkyl)methylene)bis(2,4-dialkylphenol) antioxidants. To optimize the reaction conditions
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for the formation of 6,6′-(aryl(alkyl)methylene)bis(2,4-dialkylphenol) antioxidants from 2,4-
dialkylphenol and aromatic and aliphatic aldehydes, we devoted our efforts on this research
using the reaction of 2,4-dimethylphenol (1) and 4-nitrobenzaldehyde (2a) in the catalytic
amount of the RGO-SO3H as a simple model reaction under microwave irradiation in the
presence of various reaction conditions including catalyst amount, different solvent, and power
of microwave oven (Table 1). Choosing an appropriate solvent has crucial importance for the
successful microwave-promoted in organic synthesis. To observe for optimal solvents, the model
reaction was carried out in different solvents such as EtOH, CH3CN, H2O, and without any
solvent (Table 1, entries 1-4). As shown in Table 1, entry 3 gave the best result for medium of
the model reaction. Therefore, water solvent was chosen as a reaction medium. Among the
different solvent alternatives in organic chemistry, water is extremely cheap and nontoxic. In
addition to these two general advantages, several benefits for the reaction are expected when
using water as a reaction medium for microwave-promoted approach. For example water is
rapidly heated by microwave irradiation to high reaction temperature, enabling water to act as
less polar pseudo-organic solvent.59 For optimization of microwave oven power, an increase in
power of microwave (100 to 450 W) led to decrease time of the model reaction and increased
yields of the desired products. At 300 W the yield and time of the model reaction were 96% and
9 min respectively and it similar at 450 W (Table 1, entries 5-7). In addition, we examined the
model reaction in different amounts of the catalyst (Table 1, entries 8-10). The best result was
obtained with 30 mg of the RGO-SO3H.
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Table 1. Optimizing the reaction conditions.a
Entry
1
2
3
4
5
6
7
8
RGO-SO3H (mg)
Solvent
EtOH
CH3CN
H2O
Solvent free
H2O
Power (W) Time (min) Yield (%)b
30
30
30
30
30
30
30
25
35
-
100
100
100
100
180
300
450
300
300
300
18
17
15
17
15
9
8
11
9
67
70
83
80
85
96
95
92
96
20
H2O
H2O
H2O
H2O
9
10
H2O
40
a) General reaction conditions: 2,4-dimethylphenol (1) (6 mmol), 4-
nitrobenzaldehyde (2a) (2 mmol), solvent (5-7 mL).
b) Isolated yields.
As shown in Table 2, a range of aromatic and aliphatic aldehydes were employed in order to
show the applicability and merit of this approach in the synthesis of bisphenolic antioxidants. In
order to generalize optimum reaction conditions, different derivatives of 6,6′-
(aryl(alkyl)methylene)bis(2,4-dialkylphenol) antioxidants (3a-3v) were synthesized from the
one-pot reaction of 2,4-dialkylphenols and aromatic or aliphatic aldehydes (2a-2v) in the
presence of catalytic amount of RGO-SO3H (30 mg), at power 300 W in water under microwave
irradiation. The reaction smoothly proceeded to give the corresponding bisphenolic antioxidants
in excellent yields and short reaction times relative to classical thermal conditions. As shown in
Table 2, the aromatic aldehydes with electron-withdrawing groups on the ortho- or para-
positions accelerate the time of the reaction and improved the yield of desired products compared
with the electron-donating groups on ortho- or para- positions. As can be seen in Table 2, entry
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14, the practical synthetic efficiency of this protocol was studied by reaction of 4-
formylbenzaldehyde (2n) with 2,4-dimethylphenol in the presence of the RGO-SO3H. We
observed the both of the carbonyl groups on the aromatic ring of 2n were reacted with 2,4-
dimethylphenol.
Some of the five membered ring heteroaromatic aldehydes such as furfural and pyrrole-2-
carboxaldehyde were used in the synthesis of target products (Table 2, entries 18, 19). In these
experiments, the target molecules were not obtained but the polymerization of furfural and
pyrrole-2-carboxaldehyde were happened under microwave and thermal conditions before the
production of the compounds 3r and 3s. The pyrrole and furane which in fact protonated
preferably at a ring carbon in acidic conditions, and which is polymerized under such conditions
presumably by attack of a nonprotonated pyrrole or furane aldehydes upon its conjugated acid.60,
61 Therefore, the protonation of carbonyl group on the furfural and pyrrole-2-carboxaldehyde do
not occurred. Also, it was tried that the reaction was carried out in the absence of RGO-SO3H,
but any target products observed.
In continuous of this part, we report on another application of aliphatic aldehydes for the
synthesis of bisphenolic antioxidants (Table 2, entries 20-22). As shown in these entries, this
protocol worked well when pentanal and 3-methylbutyraldehyde were employed and the
compounds 3t, and 3u were produced in 88% and 86% respectively in water under microwave
irradiation. When it was used isobutyraldehyde, the final product was observed only in 10%,
because the steric hindrance of isopropyl groups do not allow that the benzene ring attack to the
electrophilic carbon of aldehyde (Table 2, entry 22).
Also, we performed the reaction for the synthesis of bisphenolic antioxidants under
conventional thermal conditions. By comparison of the obtained results using microwave
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irradiation with conventional thermal method, it can be concluded that the reaction time was
dramatically reduced and the yield of the desired products were better. Also, for all of the
derivatives, TOF and TON of the catalyst were better in microwave conditions. Therefore,
microwave irradiation method reveals several worthwhile advantages over conventional thermal
by significantly reducing time of the reaction and increasing yield of the products.
Table 2. Synthesis of 6,6′-(aryl(alkyl)methylene)bis(2,4-dialkylphenol) antioxidants under different conditions
Microwave method a
Thermal method b
TOF TONg Time
(h-1)f
Yield
(%)c
TOF TONg
(h-1)f
Entry
R
X
Product
Time
(min)
Yield
(%)c
(min)
1
CH3
4-NO2
7
96
256
29
40
92
31
21
2
CH3
3-NO2
9
95
193
29
45
93
28
21
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3
CH3
CH3
CH3
4-Cl
6
8
6
98
93
94
300
223
290
30
90
94
89
42
44
50
30
29
29
21
22
21
4
2-Cl
30
5
2-Cl,
4-Cl
25
6
CH3
2-F
10
89
159
27
40
82
28
19
7
CH3
3-F
11
87
150
27
30
90
42
21
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8
CH3
4-Br
5
98
375
30
20
95
67
22
9
CH3
CH3
CH3
3-Br
2-Br
H
8
96
91
90
231
187
140
30
28
28
30
15
60
88
89
80
40
84
19
20
21
19
10
9
11
12
12
CH3
4-CH3
11
89
155
28
60
81
19
19
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13
CH3
3-OCH3
4-CHO
4-NO2
14
12
11
88
90
93
117
140
161
27
28
29
50
30
60
78
82
89
11
38
21
9
14d
CH3
19
15
tert-butyl
21
16
tert-butyl
3-NO2
9
91
187
28
50
90
25
21
17e
CH3
Formalde
hyde i
5
96
375
30
10
20
96
129
22
O
OH
OH
H3C
CH3
18h
CH3
Furane-2-
aldehyde i
10
--
--
--
--
--
--
CH3
CH3
(3r)
29