Hofmann N-alkylation of aniline derivatives with alcohols using ferric perchlorate immobilized on SiO2 as a catalyst through Box–Behnken experimental design

Article abstract of DOI:10.1002/aoc.4591

An efficient method for the N-alkylation of poorly nucleophilic amines using ferric perchlorate immobilized on SiO₂ as a catalyst is described. Fe(ClO₄)₃ was prepared from mixing iron(III) hydroxide and perchloric acid and adsorbed on silica gel. The catalyst was characterized using various techniques. The supported ferric perchlorate (Fe(ClO₄)₃/SiO₂) revealed high efficiency and selectivity for N-alkylation of aromatic amines with alcohols to provide alkylated amines. Various secondary amines were synthesized from primary amines and alcohols in good to excellent yields, with water as the only by-product. The optimization of the reaction conditions was investigated using the response surface method, and involving the Box–Behnken design matrix. The conditions for optimal reaction yield and time were: amount of catalyst?=?0.34?mmol, temperature?=?60°C and molar ratio of amine to alcohol?=?1.2. The catalyst was recovered and reused for five cycles without a considerable decrease in catalytic activity. The stability of the recycled catalyst was investigated. The proposed method has numerous advantages including procedure simplicity, short reaction times, low cost, good to excellent yields, reusability of the catalyst and mild and environmentally benign conditions.

Full text of DOI:10.1002/aoc.4591

Received: 4 April 2018
DOI: 10.1002/aoc.4591
Revised: 18 July 2018
Accepted: 15 August 2018
F U L L P A P E R
Hofmann N‐alkylation of aniline derivatives with alcohols
using ferric perchlorate immobilized on SiO2 as a catalyst
through Box–Behnken experimental design
Mahdi Ghanimati1 | Masumeh Abdoli Senejani1
Mohammad Ali Bodaghifard2
| Tahereh Momeni Isfahani1 |
1 Department of Chemistry, Arak Branch,
An efficient method for the N‐alkylation of poorly nucleophilic amines using
ferric perchlorate immobilized on SiO2 as a catalyst is described. Fe(ClO4)3
was prepared from mixing iron(III) hydroxide and perchloric acid and
adsorbed on silica gel. The catalyst was characterized using various techniques.
The supported ferric perchlorate (Fe(ClO4)3/SiO2) revealed high efficiency and
selectivity for N‐alkylation of aromatic amines with alcohols to provide
alkylated amines. Various secondary amines were synthesized from primary
amines and alcohols in good to excellent yields, with water as the only by‐prod-
uct. The optimization of the reaction conditions was investigated using the
response surface method, and involving the Box–Behnken design matrix. The
conditions for optimal reaction yield and time were: amount of cata-
lyst = 0.34 mmol, temperature = 60°C and molar ratio of amine to alcohol = 1.2.
The catalyst was recovered and reused for five cycles without a considerable
decrease in catalytic activity. The stability of the recycled catalyst was investi-
gated. The proposed method has numerous advantages including procedure
simplicity, short reaction times, low cost, good to excellent yields, reusability
of the catalyst and mild and environmentally benign conditions.
Islamic Azad University, Arak, Iran
2 Department of Chemistry, Faculty of
Science, Arak University, Arak, Iran
Correspondence
Masumeh Abdoli‐Senejani, Department of
Chemistry, Arak Branch, Islamic Azad
University, Arak, Iran.
Email: mabdoli@iau‐arak.ac.ir
Funding information
Islamic Azad University–Arak Branch
KEYWORDS
amines, design of experiment, Fe(ClO4)3/SiO2, heterogeneous catalyst, Hofmann N‐alkylation
1 | INTRODUCTION
purification. Furthermore, this method is harmful to the
environment due to untreated toxic alkyl halides and
Organic compounds with nitrogen atoms such as amines
play a significant role in natural products, dyes and phar-
maceuticals.[1,2] Therefore, various methods have been
developed recently for catalysed organic reactions includ-
ing the formation of a carbon–nitrogen bond because
of the biological properties and industrial applications of
amines.[3–5] The most common route is N‐alkylation of
amines with alkyl halides which produces a mixture
of amines and ammonium halides and leads to low selec-
tivity and problems involving product separation and
undesired waste.[6,7] Alkylation of amines with alcohols
instead of alkyl halides is an environmentally friendly
and efficient method for synthesizing N‐substituted
amines because water is the only by‐product.[8–10]
Ferric perchlorate is a transition metal Lewis acid that
acts as an inexpensive, easily available, odourless, non‐
toxic, reusable and stable catalyst in many organic reac-
tions. The adsorption of ferric perchlorate onto silica gel
generates a stable non‐hygroscopic material.[11] In recent
years, ferric perchlorate immobilized on silica gel as a
Appl Organometal Chem. 2018;e4591.
wileyonlinelibrary.com/journal/aoc
© 2018 John Wiley & Sons, Ltd.
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https://doi.org/10.1002/aoc.4591

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GHANIMATI ET AL.
heterogeneous catalyst has been used in organic synthe-
ses.[12–14] So, for the development of a greener and milder
procedure, herein we report a convenient method for N‐
alkylation of amines with alcohols using a catalytic
amount of ferric perchlorate immobilized on silica gel
(Fe(ClO4)3/SiO2).
The experimental design technique was used to deter-
mine the optimal conditions for reaction times and yields.
The Box–Behnken design (BBD) is a robust experimental
design method that involves fitting a model by polyno-
mial equation techniques under the response surface
method design. This method is well shown in the visual-
ization of response curve versus independent variables or
factors.[15] This design was applied for the estimation of
various parameters affecting yield and time in the N‐
alkylation of amine derivatives, and then the optimum
conditions were determined.
FIGURE 1 EDX pattern of Fe(ClO4)3/SiO2
synthesized catalyst is shown in Figure 2. There is a broad
diffraction peak at around 25° which corresponds to the
amorphous SiO2 matrix. The characteristic peaks at
2θ = 33° and 35° confirm the supporting of FeClO4 on
the SiO2 surface. The surface morphology of synthesized
Fe(ClO4)3/SiO2 was investigated using SEM (Figure 3).
The SEM image revealed a homogenous powder structure
for the catalyst.
TGA/DTA was used to investigate the thermal sta-
bility of the Fe(ClO4)3/SiO2 catalyst (Figure 4). The
weight loss (20.87%) at temperatures below 300°C can
be due to the loss of adsorbed water and surface
hydroxyl groups on silica gel support. It is obvious from
the TGA/DTA curves that the catalyst is stable even at
high temperature.
The FT‐IR spectrum of synthesized Fe(ClO4)3/SiO2 is
shown in Figure 5. The spectrum displays a band at
1629 cm−1 corresponding to the stretching vibrational
mode of H─O─H adsorbed layer. Furthermore,
stretching vibration bands in the range 3100–3600 cm−1
are attributed to both symmetric and asymmetric modes
of O─H bonds. The spectrum displays characteristic
asymmetric stretching bands at 1094 cm−1 and symmetric
stretching bands at 960, 807 and 464 cm−1 for the
Si─O─Si group.
2 | RESULTS AND DISCUSSION
In continuation of our studies of mild and green synthesis
of heterocyclic compounds,[16–20] herein we report a new,
efficient and environmentally friendly method for the
synthesis of N‐alkylated amines using Fe(ClO4)3/SiO2 as
catalyst (Scheme 1).
First, Fe(ClO4)3 was prepared by mixing iron(III)
hydroxide and perchloric acid and adsorbed on silica gel
(Scheme 2). The resulting Fe(ClO4)3/SiO2 was character-
ized using Fourier transform infrared (FT‐IR) spectros-
copy, X‐ray diffraction (XRD), field emission scanning
electron microscopy (SEM), thermogravimetric analysis
(TGA) and energy‐dispersive X‐ray (EDX) analysis.
The presence of Si, Fe, Cl and O atoms was confirmed
using EDX analysis (Figure 1). The XRD pattern of the
For the optimization of the reaction conditions, the N‐
alkylation of aniline (1 mmol) with benzhydrol (1 mmol)
in the presence of 0.4 g of the catalyst was selected as a
model reaction. Selected results from our experiments
are presented in Table 1. An initial optimization indicates
that chloroform is more suitable than other solvents. In
SCHEME 1 N‐Alkylation of aniline derivatives using Fe(ClO4)3/
SiO2 as catalyst
SCHEME 2 Synthesis of Fe(ClO4)3/
SiO2

GHANIMATI ET AL.
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FIGURE 2 XRD pattern of Fe(ClO4)3/
SiO2
benzhydrol. In this regard, Table 2 presents the level of
parameters, experimental design matrix and results. The
input factors and levels were applied to the reaction opti-
mization process. This process was: (A) the molar ratio
(1, 1.2 and 1.4), (B) the amount of catalyst (0.15, 0.3 and
0.45 g) and (C) the temperature (30, 45 and 60°C). The
response function (y) was a greater yield and a shorter
reaction time for N‐alkylation of aniline.
In order to obtain the optimum conditions, the BBD
was used for optimization. The examined variables were
distinguishable, and the interconnections between them
were analysed.
Response surface methodology and the BBD were
applied to create the coupled effect of the three factors on
the reaction process and to define optimal values for the
system. The results obtained from the BBD are presented
in Tables 3 and 4. The quality of the proposed model was
evaluated by analysis of variance (ANOVA) at 95% confi-
dence level. Regarding the ANOVA test results, the process
parameters with a p‐value of less than 0.05 are deemed to
be significant and have important effects on the yield and
time of the synthesis. The results that showed B, C, BC,
A2 and B2 are very significant in the model.
FIGURE 3 SEM image of Fe(ClO4)3/SiO2
addition, it was found that Fe(ClO4)3/SiO2 is an efficient
catalyst to give the product in excellent yield and short
reaction time.
The polynomial regression model was utilized to fit the
terms of coded values (A, B, C) with yield (%) and reaction
time as the response value using the following equations:
2.1 | Statistical Analysis and Model
Fitting
yðTimeÞ ¼ þ333:33 − 2:5A − 128:75B − 88:75C − 2:5AB
−12:5AC þ 55:0BC þ 28:33A2 þ 120:83B2 − 4:17C2
Herein, a three‐level 15‐run BBD using Design‐Expert
7.0.0 Trial software (Stat‐Ease Inc., Minneapolis) was
used to analyse the effect of various reaction parameters,
namely molar ratio of amine to alcohol, temperature and
amount of catalyst, on the N‐alkylation of aniline with
R2 ¼ 0:9987 Adjusted R2 ¼ 0:9964
yðyieldÞ ¼ þ87:33 þ 1:12A þ 13:62B þ 13:25C − 1:75AB
þ1:50AC þ 3:00BC − 8:04A2 − 11:04B2 − 13:29C2
R2 ¼ 0:9965 Adjusted R2 ¼ 0:9903

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GHANIMATI ET AL.
FIGURE 4 TGA and DTA curves of Fe(ClO4)3/SiO2
FIGURE 5 FT‐IR spectrum of Fe(ClO4)3/SiO2
TABLE 1 Optimization of reaction conditions
Entry
Catalyst
Condition
Time (h)
Yield (%)
1
2
3
4
5
6
7
8
—
CHCl3/reflux
6
—
80
87
—
60
60
78
75
Fe(ClO4)3
CHCl3/reflux
5
Fe(ClO4)3/SiO2
Fe(ClO4)3/SiO2
Fe(ClO4)3/SiO2
Fe(ClO4)3/SiO2
Fe(ClO4)3/SiO2
Fe(ClO4)3/SiO2
CHCl3/reflux
4.5
6
Solvent‐free/25°C
Solvent‐free/60°C
Solvent‐free/120°C
CH2Cl2/reflux
EtOH/reflux
4.5
4.5
4.5
4.5

GHANIMATI ET AL.
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TABLE 2 Experimental factors, levels and results for Box–Behnken design
Levels
Low
(−1)
Central
(0)
High
(+1)
Factor
Unit
Symbol
Molar ratio
—
g
A
B
C
1
1.2
0.3
45
1.4
0.45
60
Catalyst amount
Temperature
0.15
30
°C
Independent variables
Dependent variable,
time (min)
Dependent variable,
yield (%)
A
B
C
Coded
Run level
Actual
level
Coded
level
Actual
level
Coded
level
Actual
level
Experimental Predicted Experimental Predicted
1
−1
−1
0
1
0
0.3
−1
0
30
45
60
45
30
45
30
30
45
60
45
45
45
60
60
440
610
430
350
360
620
720
450
335
290
330
335
350
250
290
436.25
611.25
435
55
50
60
82
60
58
40
51
87
78
87
88
83
81
92
53.13
51.75
59.62
82.5
2
1
−1
−1
+1
+1
−1
−1
0
0.15
0.15
0.45
0.45
0.15
0.15
0.3
3
1.2
1
+1
0
4
−1
0
358.75
355
5
1.2
1.4
1.2
1.4
1.2
1
−1
0
60.37
57.5
6
+1
0
611.25
722.5
7
−1
−1
0
39.12
52.38
87.33
76.63
87.33
87.33
81.25
81.88
92.88
8
+1
0
456.25
333.33
283.75
333.33
333.33
348.75
253.75
287.5
9
0
0.3
10
11
12
13
14
15
+1
0
0
0.3
+1
0
1.2
1.2
1.4
1.4
1.2
0
0.3
0
0
0.3
0
+1
+1
0
+1
0
0.45
0.3
0
+1
+1
+1
0.45
where y is the predicted response as reaction time and
yield; A, B and C are molar ratio, amount of catalyst and
temperature, respectively; and AB, AC and BC are the
interaction coefficients of these factors.
The optimum conditions for the minimum reaction
time of 240 min (4 h) and maximum yield of 92% are:
molar ratio of amine to alcohol = 1.18–1.2, amount of cat-
alyst = 0.34 mg and temperature = 58.29°C–(reflux con-
dition). To demonstrate the conclusions, four‐time
reactions were done using these optimal experimental
conditions. Figure 8 and Table 5 present the optimal syn-
thesis conditions.
The correlation coefficients (R2) of the two equations
are 0.9987 and 0.9965, which indicate a good linearity.
Three‐dimensional response surfaces and contour curves
can be applied for monitoring the effect of two factors
on the response reaction time and yield, which are dem-
onstrated in Figures 6 and 7. Figures 6 and 7 present
the optimal experimental conditions in terms of dark blue
and dark red for reaction time and yield, respectively. The
reaction time of N‐alkylation of aniline decreases with
increasing temperature. Also, the yield increases with
increasing temperature. As can be observed, the level at
the centre of the amount of catalyst and molar ratio is
the best level of the plots.
2.2 | Utilizing Optimal Conditions
After the optimization of the reaction conditions,
we studied the efficiency of Fe(ClO4)3/SiO2 for the
N‐alkylation of aniline derivatives with a variety of benzyl
alcohols under the optimized reaction conditions
(Table 6). A variety of aniline derivatives with electron‐

6 of 14
GHANIMATI ET AL.
TABLE 3 ANOVA for Box–Behnken quadratic model for reaction time of N‐alkylation of aniline
Source
Sum of squares
Df
Mean square
F ‐value
p‐value
Remark
Model
2.645 × 105
9
1
1
1
1
1
1
1
1
1
5
3
2
14
29389.07
50.00
430.08
0.73
< 0.0001
0.4314
Significant
A, molar ratio
50.00
B, amount of catalyst
1.326 × 105
63012.50
25.00
1.326 × 105
63012.50
25.00
1940.67
922.13
0.37
< 0.0001
< 0.0001
0.5717
C, temperature
AB
AC
625.00
625.00
9.15
0.0293
BC
12100.00
2964.10
53910.26
64.10
12100.00
2964.10
53910.26
64.10
177.07
43.38
788.93
0.94
< 0.0001
0.0012
A2
B2
< 0.0001
0.3773
C2
Residual
Lack of fit
Pure error
Cor total
341.67
68.33
325.00
108.33
13.00
0.0723
Not significant
16.67
8.33
2.648 × 105
TABLE 4 ANOVA for Box–Behnken quadratic model for yield of N‐alkylation of aniline
Source
Sum of squares
Df
Mean square
F ‐value
p‐value
Remark
Model
4130.52
10.13
9
1
1
1
1
1
1
1
1
1
5
3
2
14
458.95
10.13
1485.12
1404.50
12.25
9.00
159.17
3.51
< 0.0001
0.1198
Significant
A, molar ratio
B, amount of catalyst
1485.12
1404.50
12.25
515.07
487.11
4.25
< 0.0001
< 0.0001
0.0943
C, temperature
AB
AC
9.00
3.12
0.1375
BC
36.00
36.00
238.78
450.16
652.31
2.88
12.49
82.81
156.12
226.24
0.0167
A2
238.78
450.16
652.31
14.42
0.0003
B2
< 0.0001
< 0.0001
C2
Residual
Lack of fit
Pure error
Cor total
13.75
4.58
13.75
0.0686
Not significant
0.67
0.33
4144.93
donating as well as electron‐withdrawing groups were
N‐alkylated with isopropanol, α‐phenylethanol and
diphenylcarbinol derivatives, using Fe(ClO4)3/SiO2 as cat-
alyst, in good to excellent yields and in short reaction
times. However, the substituents had no considerable
effect on the reaction times and yields.
A plausible mechanism for N‐alkylation of aniline
derivatives with alcohols using Fe(ClO4)3/SiO2 is shown
in Scheme 3. The dehydrogenation of alcohol gives the
corresponding carbonyl compound. This oxidation pro-
cess may be carried out via electron transfer between
Fe(III) and Fe(II) ions in the presence of atmospheric

GHANIMATI ET AL.
7 of 14
FIGURE 6 Response surfaces and contour plots to predict the reaction time for N‐alkylation of aniline
oxygen. Then, the carbonyl compound undergoes con-
densation with an amine to give an imine intermediate.
Finally, the product is created by adding hydrogen to
imine and the Fe(ClO4)3/SiO2 is recycled.
The recyclability of Fe(ClO4)3/SiO2 was investigated
for N‐alkylation of aniline (1.2 mmol) with benzhydrol
(1 mmol) in the presence of 0.34 g of the catalyst under
the optimized conditions. After completion of the reac-
tion, the reaction mixture was filtered to separate the cat-
alyst, which was washed two times with 20 ml of acetone
and then dried at 70°C in an oven for 12 h. The recycled
catalyst reused for five cycles without a considerable
decrease in catalytic activity (Figure 9).
Furthermore, the stability of the recycled catalyst was
studied using FT‐IR spectroscopy, XRD, SEM, EDX analy-
sis and TGA. The results of XRD and SEM analyses of the
recycled Fe(ClO4)3/SiO2 showed shape and size identical
to those of fresh catalyst (Figures 10 and 11). EDX analysis
also indicates that the chemical composition of the
recycled catalyst is almost unchanged after five reuses
(Figure 12). The comparison of TGA/DTA curves for fresh
and recycled catalyst shows that the thermal stability of

8 of 14
GHANIMATI ET AL.
FIGURE 7 Response surfaces and contour plots to predict product yield for N‐alkylation of aniline
the catalyst does not change after five reuses (Figure 13).
So, the recovered catalyst had no obvious change in
3 | EXPERIMENTAL
structure after five runs, as apparent from a comparison
of analyses of fresh catalyst and recovered catalyst.
3.1 | General
Finally, the efficiency of the method was compared
with some other methodologies for the N‐alkylation of
amine derivatives with alcohols (Table 7). The results of
this research prove the advantage of this procedure com-
pared to previous methods with respect to the yields and
times of reactions.
Melting points were determined using an Electrothermal
9200 apparatus. 1H NMR and 13C NMR spectra were
recorded with a 400 MHz Bruker AQS 500‐AVANCE
spectrometer using dimethylsulfoxide (DMSO) as the sol-
vent. FT‐IR spectra were recorded with a Bruker Tensor
27 FT‐IR spectrometer. Elemental analyses were

GHANIMATI ET AL.
9 of 14
TABLE 6 N‐Alkylation of aniline derivatives with alcohols using
Fe(ClO4)3/SiO2
Entry Product
Time (h) Yield (%)a M.p. (Lit.) (°C)
1
4
5
5
92
88
85
56–58 (58)[21]
2
3
75–77 (75)[22]
181–182
(182–183)[23]
FIGURE 8 Optimized process conditions
4
5
4
86
85
51–53 (52)[8]
performed using a PerkinElmer 2400 Series II CHNS/O
analyser. EDX analysis and SEM micrographs of the syn-
thesized catalyst were obtained using a Tescan Mira III.
TGA and DTA curves were measured using a TGA/DSC
1 instrument at a heating rate of 10°C min−1 from 25 to
1000°C under nitrogen atmosphere. Powder XRD pat-
terns were obtained with a PANalytical X'Pert PRO
MPD X‐ray diffractometer using a Cu tube in the range
2θ = 3–80°. All solvents and reagents were purchased
from Aldrich or Merck with a high‐grade quality and
were used without any purification. All products were
characterized using NMR and FT‐IR spectra and com-
pared with those of authentic samples.
5.5
57–59 (58–60)[24]
6
5
85
69–72 (68–71)[24]
3.2 | General Procedure for Preparation of
Ferric Perchlorate
A mixture of Fe(OH)3 (1.0 g, 9.3 mmol) and perchloric
acid (3.7 g, 37.2 mmol) was heated under reflux condi-
tions for 10 h. Then, the mixture was cooled to room tem-
perature, and ferric perchlorate was precipitated. The
(Continues)
TABLE 5 N‐Alkylation of aniline under optimal conditions
Factor
Dependent variable, time (min)
Experimental
Dependent variable, yield (%)
Experimental
Molar
Approach ratio
Amount of Temperature
catalyst (g) (°C)
(mean SD)
Predicted
(mean SD)
Predicted
BBD
1.18–1.2 0.34
58.29–(reflux condition) 240 2.5
240.012
92.25 1.47
92.05

10 of 14
GHANIMATI ET AL.
TABLE 6 (Continued)
TABLE 6 (Continued)
Entry Product
Time (h) Yield (%)a M.p. (Lit.) (°C)
Entry Product
Time (h) Yield (%)a M.p. (Lit.) (°C)
5.5 80 83–86
7
2.5
88
60–62 (61–63)[25]
15
8
6
4
4
80
84
85
100–102 (103)[26]
74–76 (75–76)[27]
97–100 (98–99)[28]
aIsolated yield.
produced pink crystals were filtered and washed with
5 ml of perchloric acid.[36]
9
3.3 | General Procedure for Preparation of
Fe(ClO4)3/SiO2
A solution of 1.0 g of Fe(ClO4)3 in ethanol (10 ml) was
added to a mixture of 10 g of silica gel (Kieselgel 40,
70–230 mesh; Merck) in ethanol (30 ml), and stirred mag-
netically at room temperature for 30 min. The solvent
was evaporated, and then the brown powder was dried
at 60°C in a vacuum drying cabinet for 1 h.[14]
10
11
12
13
5
82
85
80
Liquid (liquid)[29]
84–86 (82–84)[30]
92–95 (93–95)[31]
3.4 | General Procedure for N‐Alkylation
of Aniline Derivatives using Fe(ClO4)3/SiO2
A mixture of amine (1.2 mmol), alcohol (1 mmol) and
Fe(ClO4)3/SiO2 (0.34 g) in CH3Cl (15 ml) was stirred
and heated under reflux conditions for an appropriate
time. The progress of the reaction was followed by TLC
(petroleum ether–ethyl acetate, 7/1). After completion of
the reaction, the reaction mixture was cooled to room
temperature and filtered to isolate the catalyst. The crude
product was recrystallized from dichloromethane to
afford the pure compound.
5.5
6
3.5 | Selected Spectroscopic Data
14
5
84
119–121
(120–121)[32]
3.5.1 | N‐(Diphenylmethyl)aniline
(entry 1)
FT‐IR (KBr, νmax, cm−1): 3379 (N─H), 3026 (C─H aro-
matic), 2925 (C─H aliphatic), 1597 and 1494 (C═C aro-
matic), 1269 (C─N). 1H NMR (300 MHz, CDCl3, δ,
ppm): 7.70–7.65 (m, 10H, Ar─H), 7.20–7.07 (m, 5H,
Ar─H), 5.86 (s, 1H, C─H), 4.45 (brs, 1H, N─H).
(Continues)

GHANIMATI ET AL.
11 of 14
SCHEME 3 Plausible mechanism for
N‐alkylation of aniline derivatives with
alcohols using Fe(ClO4)3/SiO2
CDCl3, δ, ppm): 7.32–7.20 (m, 10H, Ar─H), 7.02 (d, 2H,
J = 6.4 Hz, Ar─H), 6.79 (d, 2H, J = 6.4 Hz, Ar─H), 5.78
(s, 1H, C─H), 3.82 (brs, 1H, N─H).
3.5.3 | N‐(Diphenylmethyl)‐4‐nitroaniline
(entry 3)
FT‐IR (KBr, νmax, cm−1): 3404 (N─H), 3077.97 (C─H aro-
matic), 2911 (C─H aliphatic), 1599 and 1463 (C═C aro-
matic), 1508 and 1303 (NO2), 1279 (C─N). 1H NMR
(300 MHz, CDCl3, δ, ppm): 7.39–7.27 (m, 10H, Ar—H),
7.13 (d, 2H, J = 6.4 Hz, Ar─H), 6.67(d, 2H, J = 6.4 Hz,
Ar─H), 5.36 (s, 1H, C─H), 3.86 (brs, 1H, N─H).
FIGURE 9 Recyclability of Fe(ClO4)3/SiO2 in the synthesis of N‐
(diphenylmethyl)aniline
3.5.2 | N‐(Diphenylmethyl)‐4‐
3.5.4 | N‐(1‐Phenylethyl)‐4‐bromoaniline
chloroaniline (entry 2)
(entry 6)
FT‐IR (KBr, νmax, cm−1): 3295 (N─H), 3059 (C─H aro-
matic), 2953 (C─H aliphatic), 1664 and 1488 (C═C aro-
FT‐IR (KBr, νmax, cm−1): 3385 (N─H), 3026 (C─H
aromatic), 2925 (C─H aliphatic), 1596 and 1493 (C═C
1
1
matic), 1264 (C─N), 758 (C─Cl). H NMR (300 MHz,
aromatic), 1269 (C─N), 697 (C─Br). H NMR (300 MHz,
CDCl3, δ, ppm): 7.55–7.50 (m, 5H, Ar─H), 7.23 (d, 2H,
J = 8.4 Hz, Ar─H), 6.83 (d, 2H, J = 8.4 Hz, Ar─H), 4.28
(q, 1H, J = 6.9 Hz, C─H), 3.89 (brs, 1H, N─H), 1.64 (d,
3H, J = 7.1 Hz, CH3).
3.5.5 | N‐((4‐Chlorophenyl)
phenylmethyl)‐4‐bromoaniline (entry 15)
FT‐IR (KBr, νmax, cm−1): 3382 (N─H), 3030 (C─H
aromatic), 2924 (C─H aliphatic), 1618 and 1489 (C═C
aromatic), 1284 (C─N), 818 (C─Cl), 701 (C─Br). 1H
NMR (300 MHz, CDCl3, δ, ppm): 7.59–7.32 (m, 11H,
Ar─H), 6.56 (m, 2H, Ar─H), 5.82 (s, 1H, C─H), 3.00
(brs, 1H, N─H). 13C NMR (75 MHz, DMSO‐d6, δ, ppm):
65.70, 114.03, 115.97, 124.45, 126.94, 127.86, 128.23,
131.64, 132.28, 138.41, 141.41, 148.78, 152.56. Anal. Calcd
for C19H15BrClN (%): C, 61.36; H, 4.06; Br, 21.27, Cl, 9.53;
N, 3.77. Found (%): C, 60.17; H, 4.01; Br, 20.16; Cl, 9.95;
N, 4.07.
FIGURE 10 SEM image of recycled Fe(ClO4)3/SiO2

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GHANIMATI ET AL.
FIGURE 11 XRD pattern of recycled
Fe(ClO4)3/SiO2
4 | CONCLUSIONS
In summary, ferric perchlorate adsorbed on silica gel was
used as a heterogeneous catalyst for the N‐alkylation
of aniline derivatives using alcohols, with the only by‐
product being water. A variety of aniline derivatives with
electron‐donating as well as electron‐withdrawing groups
undergo N‐alkylation with isopropanol, α‐phenylethanol
and diphenylcarbinol derivatives using Fe(ClO4)3/SiO2
in good to excellent yields and in short reaction times.
High yields, simple conditions, and green and reusable
catalyst are advantages of this method.
FIGURE 12 EDX pattern of recycled Fe(ClO4)3/SiO2
FIGURE 13 TGA and DTA curves of
recycled Fe(ClO4)3/SiO2

GHANIMATI ET AL.
13 of 14
TABLE 7 Comparison of efficiency of various catalysts used in N‐alkylation of aniline derivatives with alcohols
Entry
Catalyst
Time (h)
Yield (%)
Condition
1
2
3
4
5
6
7
8
Fe(ClO4)3/SiO2
Ph2PCl/imidazole/I2
Montmorillonite
Iridium complex/K2CO3
Pd/Fe2O3
4–6
80–92
CHCl3, reflux (this work)
CH2Cl2, reflux[8]
0.25–48
1–30
12–24
2–28
24–28
5–63
24
50–94
39–99
1,4‐Dioxane, 150°C[7]
19–95
2,2,2‐Trifluoroethanol, 100°C[9]
Solvent‐free, 140–170°C[10]
Solvent‐free, air, 130–150°C[33]
120°C, N2 (5 atm), toluene[34]
Solvent‐free, N2, 120°C[35]
72–99
CsOH⋅H2O
26–95
Au/TiO2
50–98
Ph2CHBr
Trace to 96
[14] M. Heravi, F. Behbahani, J. Iran. Chem. Soc. 2007, 4, 375.
ACKNOWLEDGEMENT
[15] J. P. Maran, S. Manikandan, C. V. N. Ivetha, R. Dinesh, Arab. J.
Chem. 2017, 10, S1145.
We are grateful to the Islamic Azad University–Arak
Branch for its financial support.
[16] M. Keshavarz, M. Abdoli‐Senejani, S. Hojati, M. Moosavifar,
Org. Prep. Proced, Int. 2017, 49, 549.
ORCID
[17] N. Azizi, F. Abbasi, M. Abdoli‐Senejani, Mater. Chem. Phys.
2017, 196, 118.
Masumeh Abdoli Senejani
8536-9218
Mohammad Ali Bodaghifard
9732-4746
http://orcid.org/0000-0001-
http://orcid.org/0000-0001-
[18] S. H. Siadatifard, M. Abdoli‐Senejani, M. A. Bodaghifard,
Cogent Chem. 2016, 2, 1188435.
[19] A. Mobinikhaledi, M. A. Bodaghifard, S. Asadbegi, Mol. Divers.
2016, 20, 461.
[20] M. A. Bodaghifard, A. Mobinikhaledi, S. Asadbegi, Appl.
Organometal. Chem. 2017, 31, e3557.
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How to cite this article: Ghanimati M, Abdoli
Senejani M, Isfahani TM, Bodaghifard MA.
Hofmann N‐alkylation of aniline derivatives with
alcohols using ferric perchlorate immobilized on
SiO2 as a catalyst through Box–Behnken
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