hno3@nano sio2: an efficient catalytic system for the ... · for the synthesis of various...

Journal of Saudi Chemical Society (2015) xxx, xxx–xxx

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ORIGINAL ARTICLE

HNO3@nano SiO2: An efficient catalytic system

for the synthesis of multi-substituted imidazoles

under solvent-free conditions

* Corresponding author. Tel./fax: +98 2188041344.

E-mail addresses: [email protected], k.nikoofar@alzahra.

ac.ir (K. Nikoofar).

Peer review under responsibility of King Saud University.

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http://dx.doi.org/10.1016/j.jscs.2015.11.0061319-6103 � 2015 Production and hosting by Elsevier B.V. on behalf of King Saud University.This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Please cite this article in press as: K. Nikoofar, S.M. Dizgarani, HNO3@nano SiO2: An efficient catalytic system for the synthesis of multi-substituted imidazolsolvent-free conditions3@nano SiO2 catalyzed multi-substuituted imidazoles synthesis –>, Journal of Saudi Chemical Society (2015), http://dx.doi.org/1jscs.2015.11.006

Kobra Nikoofar *, Shekoufe Moazzez Dizgarani

Department of Chemistry, Faculty of Physics and Chemistry, Alzahra University, Vanak, P.O. Box 1993893973, Tehran, Iran

Received 23 July 2015; revised 6 November 2015; accepted 19 November 2015

KEYWORDS

Benzil;

Multi-substituted imidazole;

Benzoin;

Nano silica;

HNO3@nano SiO2, multi-

component reaction;

Green chemistry

Abstract Concentrated nitric acid supported on nano silica (HNO3@nano SiO2) has been pre-

pared via a simple procedure. The synthetic powder has been utilized as an effective catalytic system

for the synthesis of various 2,4,5-trisubstituted imidazoles under solvent-free conditions at 100 �C in

good to excellent yields. In addition, under the same reaction conditions, 1,2,4,5-tetrasubstitued

imidazoles have also been performed successfully. The recovery and reusability of HNO3@nano

SiO2 have been checked in 3 runs without activity loss. The significant features of this acidic

nanocatalyst in the reported procedure, are high yield of products, short reaction times, green reac-

tion media, and vast range of substrates usage. The proposed mechanism of the cyclo-condensation

has also been represented.� 2015 Production and hosting by Elsevier B.V. on behalf of King Saud University. This is an open access

article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

1. Introduction

Imidazole ring is one of the important motifs which has beenfound in a large number of natural products and pharmacolog-ically active compounds. Different imidazole derivatives show

many biological activities such as fungicidal [1], anti-bacterial[2], anti-tumoral [3], anti-inflammatory [4], and anti-thrombotic [5]. Also various substituted imidazoles act as plant

growth regulators [6], inhibitors of p38 MAP [7] and B-Raf

kinase [8], and glucagon receptors [9]. Omeprazole [10],Pimobendan [11], Losartan, Olmesartan, Eprosartan, andTrifenagrel [12] are some of the drugs with diverse functional-

ization around the imidazole ring. This versatile applicabilityhighlights the importance of exhibiting efficient syntheticmethods for the preparation of well-designed multi-

substituted imidazole derivatives. Japp and Radziszewskiproposed the first synthesis of the imidazole core in 1882,starting from 1,2-dicarbonyl compounds, aldehydes, andammonia to obtain 2,4,5-triphenylimidazoles [13,14]. Since

that time, numerous methods have been developed for thesynthesis of multi-substituted imidazoles using various catalystsincluding silica gel or zeolite HY [15], silica gel/NaHSO4

[16], K5CoW12O40�3H2O [17], L-proline [18], HClO4-SiO4

[19], tetrabutylammonium bromide (TBAB) [20], PEG-400 [21],MgAl2O4 [22], triphenyl(propyl-3-sulphonyl)phosphonium

es under0.1016/j.

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Figure 1 FT-IR spectra of SiO2 (a) and HNO3@nano SiO2 (b).

2 K. Nikoofar, S.M. Dizgarani

toluenesulfonate as a bronsted acidic ionic liquid [23], and nanoTiCl4-SiO2 [24]. Besides the mentioned route, other procedureshave been published for the synthesis of this heterocyclic com-

pounds such as four component condensation of aryl glyoxals,primary amines, carboxylic acids, and isocyanides on Wangresin [25], reaction of N-(2-oxo)amides with ammonium triflu-

oroacetate [26], from cyclic or acyclic 1,2-aminoalcohols via afour-step procedure involving acylation of the amine, oxida-tion of the alcohol, imine formation and cyclization [27],

thiazolium-catalyzed addition of an aldehyde to an acylimine to generate the corresponding a-ketoamide in situ fol-lowed by ring closure to the imidazole in a one-pot sequence[28], and the reaction of o-methyl-iso-urea sulfate and

2-aminoacetaldehyde-acetales in the presence of sulfuric acid[29]. Many of the so far reported procedures for the synthesisof imidazoles suffer from one or more disadvantages such as

harsh reaction conditions, poor yields, prolonged time period,use of hazardous and often expensive acid catalysts, side-reactions leading to mixtures of products (including reversed

aldol condensation and oxazole formation), lack of generality,and use of complex work-up procedures with significantamounts of waste materials [30]. Also some of the reported

procedures have been accomplished in polar solvents whichare difficult to recycle due to the substantial costs or environ-ment damage.

One aspect of clean technology is the use of environmen-

tally friendly catalysts, which could be easily recovered andreused. For this respect, nano acid catalysis has the advantageof high atom efficiency, easy product purification, and

reusability of the catalyst [31].Among them, commercial nano SiO2 has been a focus of

extensive research due to its chemical stability, large surface

area, narrow particle size distribution, non-toxicity (LD50:20,800 mg/kg), cheapness, environmentally friendly in the con-text of green synthesis, high reflectivity to visible light and

ultraviolet ray, and abundance [32]. In addition, nanometer sil-icon dioxide surface consists of silanol groups [33].

In continuation of our research activities on nanotechnol-ogy [34–38], herein we prepared a solid acid catalyst via

embedding concentrated HNO3 on nano SiO2 by a simple pro-cedure. The prepared powder, HNO3@nano SiO2, has beencharacterized and used as an effective catalyst for the synthesis

of tri- and tetra-substituted imidazole derivatives via one-potand one-step condensation reaction of benzils/benzoins, alde-hydes, ammonium acetate, and amines under solvent-free con-

ditions at 100 �C, respectively.

2. Experimental

2.1. General

Chemicals and solvents were purchased from Merck, Aldrich,and Alfa Aesar and used without further purifications. Theamorphous nano silica with the average particle size 20–30 nm and specific surface area of 180–270 m2/g was purchased

from Tecnan Company. IR spectra were recorded from KBrdisk using FT-IR Bruker Tensor 27 instrument. Melting pointswere determined on a shimadzu DSC-50 thermal analyzer and

are uncorrected. 1H NMR spectra were recorded in DMSO(d6)solvent on a Bruker drx (400 MHz) machine. Preparative layerchromatography (PLC) was carried out on 20 � 20 cm2 plates,

Please cite this article in press as: K. Nikoofar, S.M. Dizgarani, HNO3@nano SiO2: Asolvent-free conditions3@nano SiO2 catalyzed multi-substuituted imidazoles synthejscs.2015.11.006

coated with a 1 mm layer of Merck silica gel PF254, prepared

by applying the silica as slurry and drying in air. The scanningelectron microscope (SEM, model

P-IJMA) was used to char-

acterize the nano structures. Elemental analyses were deter-

mined using a Thermo-Finnigan Flash EA 1112 Series.

2.2. Preparation of HNO3@nano SiO2

In a round bottom flask, to a mixture of commercial nano SiO2

(2.5 g) in dry CHCl3 (10 mL), 1 mL of concentrated HNO3 wasadded and magnetically stirred at room temperature for

180 min. Then CHCl3 was evaporated at room pressure. Thesolid residue was heated in an oven at 100 �C for 2 h. Theobtained pale yellow solid is HNO3@nano SiO2. This synthe-sized nano catalyst (0.1 g) was titrated by a standard solution

of NaOH (0.1 N) to obtain its [H+] concentration which was4.3 meq per gram of the powder. It was also characterizedby FT-IR spectra (Fig. 1) and SEM image (Fig. 2).

2.3. General procedure for the synthesis of 2,4,5-trisubstituted

imidazoles

A mixture of benzils 1a–b (method A)/benzoins 2a–b (method B)(1 mmol), aldehydes 3a–p (1 mmol), ammonium acetate (4)(2 mmol), and HNO3@nano SiO2 (0.012 g) was stirred at 100 �Cunder solvent-free conditions. The progress of the reaction wasmonitored by TLC. After completion (2–9 h), methanol (5 mL)was added and filtered. The solid residue was washed with metha-nol (2 � 10 mL). The solvent was evaporated and the residue puri-

fied by chromatography on silica gel using pet. ether/ethyl acetate(1:4) toafford thepureproducts5a–q (65–92%,Table2,Scheme1).All the productswere characterized by comparison of theirmelting

points and spectroscopic data (FT-IR and 1HNMR)with those ofthe authentic samples in the literature.

2.3.1. 3-(4,5-Diphenyl-1H-imidazol-2-yl)-1H-indole (5o)

m.p. 310 �C; IR (KBr): t 3414, 2923, 1699, 1560 cm�1; 1HNMR (DMSO-d6): d 8.46 (d, J = 6.62 Hz, 1H, NH), 8.01

n efficient catalytic system for the synthesis of multi-substituted imidazoles undersis –>, Journal of Saudi Chemical Society (2015), http://dx.doi.org/10.1016/j.



Figure 2 SEM image of nano SiO2 (a) and HNO3@nano SiO2 (b).

Table 1 Optimization of 5c synthesis by HNO3@nano SiO2.a

Entry Condition Temp.

(�C)Time

(h)

Yield

(%)c

1 Catalyst-free/solvent-free r.t. 24 12

2 HNO3@nano SiO2

(0.007 g)/solvent-free

r.t. 24 33

3 HNO3@nano SiO2 (0.007 g)/

H2Ob

Reflux 24 –


EtOHbReflux 24 –


CH2Cl2b

Reflux 24 –


CH3CNb

Reflux 24 –


CH3OHbReflux 24 41

8 HNO3@nano SiO2


50 24 35

9 HNO3@nano SiO2


70 5 62

10 HNO3@nano SiO2


90 5 76

11 HNO3@nano SiO2 (0.007 g)/

solvent-free

100 5 82

12 HNO3@nano SiO2


100 3.45 91

13 HNO3@nano SiO2


100 3.45 91

14d HNO3@nano SiO2


100 3.45 91

15e HNO3@nano SiO2


100 5 74

16 Nano SiO2 (0.02 g)/solvent-

free

100 6 67

17 HNO3 (0.01 g)/solvent-free 100 6 25

a Benzil (1 mmol), 4-chlorobenzaldehyde (1 mmol), and ammo-

nium acetate (2 mmol) have been used.b 5 mL of each solvent has been used.c Isolated yield.d NH4OAC (3 mmol) has been used.e NH4OAC (1 mmol) has been used.

HNO3@nano SiO2 catalyzed multi-substuituted imidazoles synthesis 3

(br s, 1H, NH), 7.84 (dd, J = 6.51, 2.86 Hz, 1H, Ar-H), 7.65–7.49 (m, 4H, Ar-H), 7.44–7.09 (m, 10H, Ar-H) ppm; Anal.

Calcd. for C23H17N3: C 82.36, H 5.11, N 12.52%. Found: C81.93, H 5.03, N 12.64%.


2.4. General procedure for the synthesis of 1,2,4,5-tetrasubstituted imidazoles

A mixture of benzil (1a) (method A)/benzoin (2a) (method B)

(1 mmol), aldehydes 3 (1 mmol), ammonium acetate (4)(2 mmol), primary amines 6a–c (1 mmol), and HNO3@nanoSiO2 (0.012 g) was stirred at 100 �C under solvent-free condi-

tions for the appropriate time monitored by TLC. The work-up procedure is the same as that of tri-substituted imidazoles.The pure products 7a–p have been afforded by 70–86% yield

(Scheme 1, Table 3).

2.4.1. 1,4-Bis(1,4,5-triphenyl-1H-imidazol-2-yl)benzene (7p)

M.p. 210–211 �C; IR (KBr): t 3445.16, 29.24.99, 16.48.88,

1542.07, 00.86 cm�1; 1H NMR (DMSO-d6)): d 7.96 (d,J= 8.51 Hz, 2H, NH), 7.69–7.64 (m, 4H, Ar-H), 7.56–7.49(m, 8H, Ar-H), 7.42–7.35 (m, 4H, Ar-H), 7.35–7.18 (m, 12H,Ar-H) ppm; Anal. Calcd. for C36H34N4: C 82.72, H 6.56, N

10.71%. Found: C 82.56, H 6.64, N 10.03%.

3. Results and discussion

First, the solid catalyst HNO3@nano SiO2 has been character-ized by FT-IR spectra and SEM technique. According to theFT-IR spectra of SiO2 (Fig. 1a) and HNO3@nano SiO2

(Fig. 1b) the bands at 3337 and 3412 cm�1, assigned to thevibration of Si-OH, are related to the silanol groups in thestructure of amorphous nano SiO2, respectively. The strong

and broad band at 1089 cm�1 with a shoulder at 1178 cm�1

is usually assigned to the TO and LO modes of the Si–O–Siasymmetric stretching vibrations (Fig. 1a) [33]. The band at

1093 cm�1 in Fig. 1b, is also dependent on these asymmetricstretching vibrations. The band at 803 cm�1 can be assignedto Si–O–Si symmetric stretching vibrations. Also the bandsat 482 and 473 cm�1 in Fig. 1a and b are relevant to the O-

Si-O bending vibrations, respectively. The stretching bandsof NO2 at 1459 and 1630 cm�1 in Fig. 1b, confirmed the suc-cessful preparation of HNO3@nano SiO2. Comparison the

SEM of nano SiO2 (Fig. 2a) with HNO3@nano SiO2

(Fig. 2b) revealed that hno3 has been sited on SiO2 nanoparti-cles. The average particle size of the prepared catalyst is 20–

30 nm.To investigate the optimized reaction conditions, the

condensation of benzil (1 mmol), 4-chlorobenzaldehyde

(1 mmol), and ammonium acetate (2 mmol) to prepare




Table 2 Synthesis of 2,4,5-trisubstituted imidazoles 5a-q by HNO3@nano SiO2 (0.012 g).

Productc Ar Ar0 Method Aa Method Bb m.p. (�C)found

m.p. (�C) reported[References]

Time

(h)

Yieldd(%) Time

(h)

Yieldd(%)

5a Ph Ph 2.50 86 3 81 264–265 267–269 [18]

5b Ph 4-CH3C6H4 2.15 87 3.15 91 230–232 233–235 [18]

5c Ph 4-ClC6H4 3.45 91 3.30 90 257–258 262–264 [18]

5d Ph 4-NO2C6H4 8.30 61 9 71 192–194 199–201 [18]

5e Ph 3-NO2C6H4 7.20 66 8.20 67 298–300 >300 [18]

5f Ph 4-OHC6H4 4.15 87 4.15 91 230–232 232–233 [18]

5g Ph 3-OHC6H4 5.15 83 5.30 76 250–253 258–260 [18]

5h Ph 4-OCH3C6H4 4.30 82 5.40 86 216–218 220–223 [18]

5i Ph 2-OCH3C6H4 2.45 84 3.30 77 201–204 210–211 [18]

5j Ph 4-(NCH3)2C6H4 2.30 84 2 86 252–253 256–259 [18]

5k Ph 2-OH-5-BrC6H3 4.50 87 4.45 81 178–180 186–187 [18]

5l Ph 2-OH-5-

NO2C6H3

6.25 72 6.50 67 215–216 219–220 [18]

5m Ph 1-naphthyl 2.40 86 2.15 76 287–288 297 [20]

5n Ph 2-furyl 2.20 83 2.10 73 237–238 242 [20]

5o Ph NH

6.30 74 7 67 310 –

5p 4-

OCH3C6H4

4-BrC6H4 5.10 77 5.20 72 161–163 160–161 [21]

5q 4-

OCH3C6H4

4-CH3C6H4 2.50 92 2.30 84 209–210 213–214 [18]

a Benzils (1 mmol), aldehydes (1 mmol), and NH4OAc (2 mmol) at 100 �C under solvent-free conditions.b Benzoins (1 mmol), aldehydes (1 mmol), and NH4OAc (2 mmol) at 100 �C under solvent-free conditions.c All products were characterized by comparison of their spectroscopic data (FT-IR, 1H NMR) with those reported in literature.d Isolated yield.

Ar

O

O

O

OH

Ar

+ + NH4OAcHNO3@nano SiO2 (0.012 g)

Solvent-free, 100 °C ArNH

NAr Ar'

Ar

Ar

Ar' CHO1a-b

2a-b

3a-p 4 5a-q

Ph

O

O

Ph

Ph

O

OH

Ph

+ + NH4OAcPh

N

NPh Ar'RNH2 +

RAr' CHO

HNO3@nano SiO2 (0.012 g)

Solvent-free, 100 °C1a

2a

3 6a-c 7a-p4

Scheme 1 Synthesis f 2,4,5-trisubstituted imidazoles (5a–q) and 1,2,4,5-tetrasubstituted imidazoles (7a–p) in the presence of HNO3@-

nano SiO2.


2-(4-Chlorophenyl)-4,5-diphenyl-1H-imidazole (1c) has beenchosen as the model. The results are summarized in Table 1.

As could be seen at entry 1, the reaction progress is very littlein the absence of the catalyst. Optimization of the solventeffect confirmed that the reaction didn’t proceed well in the

presence of different solvents (entries 2–7). Checking thetemperature effect indicates that 100 �C is the best selection(entries 8–11). The nanocatalyst amount study in the model


reaction progress, indicated that the best amount is 0.012 gof HNO3@#132;nano SiO2 (entries 12, 13). The NH4OAc

amount optimization has also been investigated and the resultconfirmed that 2 mmol is the best quantity (entries 14, 15). Theefficacy of the synthesized nanocatalyst has also been demon-

strated by performing the model reaction in the presence ofsole nano SiO2. The results affirmed that setting HON3 onnano SiO2 surface, enhanced its catalytic activity (entry 16).




Table 3 Synthesis of 1,2,4,5-tetraubstituted imidazoles by HNO3@nano SiO2 (0.012 g).

Productc Ar0 R Method Aa Method Bb m.p. (�C) found m.p. (�C) reported [References]

Time (h) Yieldd(%) Time (h) Yieldd(%)

7a Ph Ph 3.30 77 4 76 219–221 220–221 [21]

7b 4-CH3C6H4 Ph 4.30 76 5 82 187–188 189 [39]

7c 4-ClC6H4 Ph 3 86 3.50 81 159–162 164–166 [18]

7d 4-NO2C6H4 Ph 6.30 68 7.20 71 189–190 191–193 [18]

7e 3-NO2C6H4 Ph 5.20 72 5.30 73 240–243 248–250 [18]

7f 4-OHC6H4 Ph 4.20 77 5 83 287–288 282–285 [22]

7g NH

Ph 5.10 76 5.30 74 220–222 219–221 [40]

7h Ph PhCH2 3.20 82 3.30 78 160–160 163–165 [18]

7i 4-CH3C6H4 PhCH2 3.10 84 3 83 168–169 167–168 [18]

7j 4-ClC6H4 PhCH2 3.50 86 3.10 86 156–158 161–163 [18]

7k 4-OHC6H4 PhCH2 4.30 84 4.50 77 130–132 134–136 [24]

7l 4-OCH3C6H4 PhCH2 3 83 4.30 72 150–152 155–158 [23]

7m Ph CH3 2 80 2.30 79 147–148 146–147 [18]

7n 4-CH3C6H4 CH3 2.30 77 3 81 220–221 222–223 [18]

7o 4-BrC6H4 CH3 6.20 70 6.30 77 190–192 197–198 [23]

7pe CHOOHC Ph 5.45 75 – – 210–211 –

a Benzil (1 mmol), aldehydes (1 mmol), amines (1 mmol), and NH4OAc (2 mmol) at 100 �C under solvent-free conditions.b Benzoin (1 mmol), aldehydes (1 mmol), amines (1 mmol), and NH4OAc (2 mmol) at 100 �C under solvent-free conditions.c All products were characterized by comparison of their spectroscopic data (FT-IR, 1H NMR) with those reported in literature.d Isolated yield.e Benzil (2 mmol), terephthalaldehyde (1 mmol), aniline (2 mmol), and NH4OAc (2 mmol) at 100 �C under solvent-free conditions.


The model reaction has also been performed in the presence ofconcentrated HNO3 (0.01 g) at 100 �C under solvent-free con-

ditions (entry 17), but the results were not satisfactory. There-fore, performing the reaction of benzils (1 mmol), aldehydes(1 mmol), NH4OAc (2 mmol), and HNO3@nano SiO2

(0.012 g) at 100 �C under solvent-free conditions has been cho-sen as the optimized situation for our procedure.

Under optimized conditions, the reactions of benzils 1a–b

with different aldehydes 3a–p, and NH4OAc (4) were carriedout until maximum progression of the reactions (Scheme 1).As can be seen (Table 2, method A) different benzils and alde-hydes containing electron donating and withdrawing groups

accomplished the condensation in good to excellent yields(70–93%) within almost a short reaction time (15–120 min).

To explore the scope of this condensation reaction, we stud-

ied the reactions of benzoins (1 mmol), aldehydes (1 mmol),NH4OAC (2 mmol), and HNO3@nano SiO2 (0.012 g) at100 �C under solvent-free conditions (Table 2, method B).

The results affirmed that benzoins, as other candidate of dike-tones, underwent this one pot multicomponent synthesis withdifferent aldehydes bearing either electron-releasing orelectron-withdrawing substituents in the ortho, meta or para

positions to afford 2,4,5-trisubstituted imidazoles within 2–9 h in good yields (67–91%). As could be seen in Table 2, inaddition with various benzaldehyde derivatives, heteroaro-

matic aldehydes such as 2-furaldehyde (3n), and 1H-indole-3-carbaldehyde (3o) produced their correspondence imidazoles5n, 5o successfully

In the next step, the applicability of this method, has beenexamined for the synthesis of 1,2,4,5-tetrasubstituted imida-zoles via the one-pot, four-component condensation reaction

of benzil (1a)/benzoin (1b) (1 mmol), aldehydes 3 (1 mmol),


primary amines 6a-c (1 mmol), and ammonium acetate (4)(2 mmol) in the presence of HNO3@nano SiO2 (0.012 g) at

100 �C under solvent-free conditions (Table 3). As considered,the respective adducts have been prepared successfully in bothmethods A and B. The data revealed that, besides different

electron-donating and electron-withdrawing hetero/aromaticaldehydes, terephthalaldehyde (3r) gave 1,4-bis(1,4,5-triphenyl-1H-imidazol-2-yl)benzene (7p) successfully. The benzoin

(2a) failed to prepare the 7p adduct (Table 3, method B).Preparation of 7p affirms the selective operation of thenanocatalyst, as only 7p has been obtained and no 4-(1,4,5-triphenyl-1H-imidazol-2-yl)benzaldehyde has been observed.

This selectivity is strengthened when both the molar ratios of1:1:1:2 and 1:2:2:2 for terephthalaldehyde/benzil/aniline/NH4

OAc have been consumed. The results demonstrated that in

both cases, 7p was the only adduct. Proper condensation ofaromatic and aliphatic primary amines is another consequenteffect of HNO3@nano SiO2. It must be mentioned that no sig-

nificant diversity in time and/or yields of the reactions havebeen observed neither in the reaction of benzils (method A)or benzoins (method B), nor about electron-donating orelectron-withdrawing aldehydes in the synthesis of both tri-

and tetrasubstituted imidazoles.The Plausible mechanism for the catalytic activity of

HNO3@Nano SiO2 in the synthesis of multisubstituted imida-

zoles has been proposed at Schemes 2 and 3. In order toexplain the route for both benzils/benzoins, we representedtrisubstituted imidazole preparation in the presence of benzils

(Scheme 2) and the tetrasubstituted analogous by benzoins(Scheme 3). As could be seen in Scheme 2, the synthesizednanocatalyst as a mild binary Lewis and also protic acid acti-

vator, interacted with the carbonyl of aldehydes 3 to activate it




Ar' H

O

Ar' NH2

H OH

H2O

Ar'

NH2NH2

Ar O

Ar

Ar'HN

Ar

O+

Ar

O+H

1,5 [H shif t]

Ar'

N

NH

Ar

Ar

HNO3@nano SiO2 :

Ar'

NH

NH4OAc

NH3

H

2H2O

3 A B

C

D

41

O

Ar' N

ArAr

H N

E5

NH4OAc4

H

NH

NH3

2

Scheme 2 Proposed mechanism for the synthesis of trisubstituted imidazoles.

Ar' H

O

NH2R

Ar' NHR

H OH

H2O

Ar'

NHRNH2

Ph O

Ph

Ar'HN

Ph

OHPh

O

HAr'

N

NR

Ph

Ph

HNO3@nano SiO2 :

Ar'

NR

NH4OAc

NH3

H2O

3

6

A B

C

D

42

OH

NHRAr'

HN

Ph

OHPh

H NR

H2O

Ar' N

PhPh

H NR

EF7HOHO

H2O

Scheme 3 Plausible mechanism for tetrasubstituted imidazoles synthesis.

Figure 3 Reusability of HNO3@nano SiO2 in the synthesis of 7a.


for the nucleophilic attack of ammonia, created from NH4OAc

(4), to perform the hydroxyl amine intermediate A whichfollowed by H2O releasing yielded the imine intermediate B.Subsequent condensation with ammonia forms the diamine

intermediate C, that attack to the activated benzils 1 to pro-duce D. The reaction proceed via loosing H2O and nanocata-lyst to form E. The final 1,5 [H shit] generated trisubstitutedimidazoles 5. In Scheme 3, the diamine C attacks the activated

benzoin (2a) to perform the intermediate D. Preparation ofintermediate E, involves the intramolecular nucleophilic attackof amine part to the activated carbon followed via a two-step

H2O and nanocatalyst release to provide the products 7.The reusability of the recovered catalyst has been studied as

another efficient and important aspect of this protocol.

For this reason, the HNO3@Nano SiO2 was recovered fromthe reaction mixture of 1,2,4,5-tetraphenyl-1H-imidazole (7a)by the addition of CH3OH (10 mL), filtration and washing

the solid residue with more CH3OH (2 � 5 mL). Therecovered catalyst was dried overnight at room temperature.The obtained solid could be reused and recycled over 3 runswith almost no activity decrease. As could be seen in Fig. 3,


the recovered nanocatalyst catalyzed the one-pot four-component reaction to obtain 7a within 77, 77, and 75% yieldduring three separation and reaction cycles.

4. Conclusion

In this paper, we have developed a simple and efficient one-potmulticomponent methodology for the synthesis of 2,4,





5-trisubstituted and 1,2,4,5-tetrasubstituted imidazoles usingHNO3@nano SiO2 as heterogeneous and eco-friendly solidacid catalyst under solvent-free conditions. The nanocatalyst

has been synthesized via a simple mixing procedure and char-acterized by titration, FT-IR, and SEM techniques. The greenreaction media in the absence of any hazardous solvents, utiliz-

ing HNO3@nano SiO2 as a heterogeneous, readily availableand eco-friendly solid acid catalyst, simple experimental proce-dure, and wide-spread substrate usage, are highlighted features

that make this protocol interesting for organic chemists.

Acknowledgment

The authors are grateful to the Research Council of AlzahraUniversity for the financial support of this work.

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