Boric Acid Catalysed Synthesis of Benzimidazole Derivatives

Report on a project carried out as a part of curriculum (CHO- 631 PR:

Research Project) for the degree of “Master of Science in Organic Chemistry” at
Department of Chemistry, Agasti Arts, Commerce & Dadasaheb Rupwate Science
College, Akole. Tal.- Akole, Dist.- Ahilyanagar, (422 601 ).
Submitted by
Miss. Nilam Khushalsing Pardeshi
M. Sc. II (Organic Chemistry) Sem.- III
Department of Chemistry
Agasti Arts, Commerce & Dadasaheb Rupwate Science College, Akole
Tal.- Akole, Dist.- Ahilyanagar 422601
2024 - 2025
Under the guidance of
Prof. Wakchaure Arun Lahanu
Asst. Professor, Department of Chemistry,
Agasti Arts, Commerce & Dadasaheb Rupwate Science College, Akole
Tal.- Akole, Dist.- Ahilyanagar 422 601

SAVITRIBAI PHULE PUNE UNIVERSITY

Oct. / Nov. – 2024

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 CANDIDATES DECLARATION

I hereby declared that, research project entitled “Boric Acid

Catalysed Synthesis of Benzimidazole Derivatives”, submitted to the
Department of Chemistry, Agasti Arts, Commerce & Dadasaheb
Rupwate Science College, Akole Tal.- Akole, Dist.- Ahilyanagar 422 601,
in partial fulfillment of degree of Master of Science, has not been
submitted to any other University or institution. This Work carried out
at the Department of Chemistry, Agasti Arts, Commerce & Dadasaheb
Rupwate Science College, Akole. Tal.- Akole, Dist.- Ahilyanagar, 422
601.

Miss. Nilam Khushalsing Pardeshi

M. Sc. II (Organic Chemistry)
Department of Chemistry,
Agasti Arts, Commerce & Dadasaheb Rupwate Science College, Akole
Tal. - Akole, Dist.- Ahilyanagar, 422 601.

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 CERTIFICATE

This is to certify that the work incorporated in this project

entitled “Boric Acid Catalysed Synthesis of Benzimidazole Derivatives”

being submitted to Department of Chemistry, Agasti Arts, Commerce

And Dadasaheb Rupwate Science College, Akole as partial fulfillment

of requirement for the degree of Master of Science in Organic

Chemistry by Miss. Nilam Khushalsing Pardeshi is carried out under

my supervision at Department of Chemistry, Agasti Arts, Commerce

And Dadasaheb Rupwate Science College, Akole. Tal.- Akole, Dist.-

Ahilyanagar, (422 601) during the academic year 2024-2025.

Prof. Wakchaure Arun Lahanu

Assistant Professor

Department of Chemistry,

Agasti Arts, Commerce & Dadasaheb Rupwate Science College, Akole

Tal.- Akole, Dist. – Ahilyanagar, 422 601.

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 साहसे श्री: प्रतिवसति|
Akole Taluka Education Society’s,
Agasti Arts, Commerce & Dadasaheb Rupwate Science College, Akole.
Tal.- Akole, Dist.- Ahilyanagar, 422 601.
Department of Chemistry

CERTIFICATE

This is to certified that, the work incorporated in the research project report

entitled “Boric Acid Catalysed Synthesis of Benzimidazole Derivatives” submitted

by Miss. Nilam Khushalsing Pardeshi for the award of the degree of Master of

Science in Organic Chemistry to Department of Chemistry, Agasti Arts, Commerce

and Dadasaheb Rupwate Science College Akole, was carried out by the candidate

under the supervision of Prof. Arun Lahanu Wakchaure, (Department of Chemistry),

Agasti Arts, Commerce and Dadasaheb Rupwate Science College, Akole. Tal.-

Akole, Dist.- Ahilyanagar, (422 601) during the academic year 2024-2025.

Dr. S. M. Sonawane Examiner

1) Prof…………………………

2) Prof…………………………

3) Prof…………………………

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 Acknowledgement

It is my great pleasure to thank many people who have assisted me

through this short journey. First and foremost, I wish to thank my advisor Prof.

Arun L. Wakchaure, for his guidance, support, encouragement, and inspiration to

my project studies. He is a fantastic mentor who was influential for my interest,

and my ability to grasp the essence of organic chemistry. He teaches me

everything he knows and always encourages me to think creatively and be

prepared to learn new scientific method. I am grateful to him for all the way in

which he has prepared me to move forward in my career and life.

I was very fortunate to work with a fantastic group of Chemistry

Department, Akole College. My thanks to Dr. S. M. Sonawane, Prof. S. D.

Kasar, Prof. Mrs. S. M. Bangal, Prof. P. H. Naikwadi, Prof. Mrs. J. S. Shinde, Prof.

P. R. Mali, Prof. S. G. Muthe, Prof. Mrs. A. S. Ankaram and Prof. T. R. Gaje for

devoting their precious time and made much valuable suggestion which indeed

helped me during this project work. A special thank goes to Awari Mayur and

Bhalekar Gayatri for their help and friendship.

I also take this opportunity to thank all respected teachers from the

department who always helped me to move ahead and were always source for

motivation and spiritual energy. Along with them I sincerely thanks to all my

friend, colleagues in M. Sc.- II, Lab. Assistant Mr. K. L. Bhalerao, Lab. Attendant

Mr. S. S. Kathade, Mrs. S. A. Shewale, Mr. V. P. Deshmukh, Mr. Ganesh

Deshmukh for their constant support and continuous motivation. My apologies to all

those who have helped me but I forgot to acknowledge.

Nilam Khushalsing Pardeshi

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 INDEX

Sr. No. Topic Name Page No.

1 Introduction 7

2 Literature Review 9

3 Material and Methods 11

4 Result and Discussion 12

5 Thin Layer Chromatographic Data 14

6 Spectrometric Identification (IR) 16

7 Conclusion 19

8 References 20

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 1. Introduction

The preparation of benzimidazoles has gained considerable attention in recent

years. The benzimidazole is found in a variety of naturally occurring compounds and is of

significant importance in medicinal chemistry. Their diverse applications include as

potential antitumor agents[1], antimicrobial agents[2], angiotensin II inhibitors[3-5]. In

addition, benzimidazoles are very important intermediates in organic reactions [6].

Several methods have been reported for the synthesis of benzimidazoles [7]. The

traditional synthesis of benzimidazole involves the reaction between o-phenylenediamine

and a carboxylic acid or their derivatives at elevated temperature in the presence of strong

acids such as polyphosphoric acid [8] or mineral acids [9] and thermal or acid promoted

cyclization of N-(N-arylbenzimidoyl)-1,4-benzoquinoneimines [10]. Recently direct

condensation of o-aryldiamines and aldehydes is the most convenient method for the

preparation of these compounds. In this context some methods and catalysts have been

reported such as indium triflate [11], iodine [12], cetylpyridinium bromide [13], PEG 400

[14], (bromodimethyl)sulfonium bromide [15] and ammonium acetate [16]. Although,

these approaches are satisfactory for synthesis of benzimidazoles, the harsh reaction

conditions, expensive reagents, use of toxic organic solvents and long reaction times limit

the use of these methods.

In recent years, water-mediated organic synthesis without using organic solvents

has become one of the most important aspects in organic chemistry in order to meet the

environmental demands. Carrying out organic synthesis in aqueous phase is highly

challenging both from the synthetic view point and also from the impact of the

environmental pollution [17]. During the course of our systematic studies directed

towards the development of environmentally friendly procedures for several important

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organic transformations [18-20], we now describe a simple, general and efficient protocol

for the synthesis of 2-substituted benzimidazoles using boric acid in water at room

temperature (Scheme).

O
NH2 N
Boric acid
Ar
Ar H R.T., H2O
N
NH2 H

o- Phenylenediamine Aldehyde Benzimidazole

Boric acid (H3BO3) is a useful and environmentally benign catalyst which has

been successfully utilized in numerous reactions, for example, the aza Michael addition

[21], Biginelli reaction [22] transesterification of ethyl acetoacetate [23], mannich

reaction [24] and synthesis of a–aminophosphonates and dibenzoxanthenes by our group

[25-26]. It offers milder conditions relative to common mineral acids. Boric acid is a

readily available and inexpensive reagent and can conveniently be handled and removed

from the reaction mixture. Thus, the remarkable catalytic activities together with its

operational simplicity make it the most suitable catalyst for the reaction of diamines with

aldehydes.

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 2. Literature Review

1. (a) Saha, P.; Ramana, T.; Purkait, N.; Ali, M. A.; Paul, R.; Punniyamurthy, T. J. Org.

Chem. 2009, 74, 8719.

(b) Jithendra Kumara, K. S.; Krishnamurthy, G.; Kumara Swamy, B. E.; Shashi Kumar,

N. D.; Naik, S.; Krishna, B. S.; Naik, N. Appl. Organomet. Chem. 2017, 31, e3549.

NH2
N
(CH3COO)2Cu
R'COH R'

NH2 N
H

2. Sapkal, B. M.; Labhane, P. K.; Satam, J. R. Res. Chem. Intermed. 2017, 43, 4967.

NH2 O
N
Nano BiOCl
R
R H 35oC, H2O,
Ultrasound ))))) N
NH2 H

3. Alinezhad, H.; Salehian, F.; Biparva, P. Synth. Commun. 2012, 42, 102.

NH2 O
N
ZnO NPs 2 mol%
R R H
H OH 70oC, Solvent free
NH2 N
H

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4. Trivedi, R.; De, S. K.; Gibbs, R. A. J. Mol. Catal. A: Chem. 2006, 245,01 8.

NH2 O
In(OTf)3 N

R
H R
NH2 N
H

5. Saberi, A. Iran. J. Sci. Technol. 2015, 39, 7

MW
Ze o
lite

NH2 O
N
MW
R
HO R Silica
NH2 N
H
MW
a
l u min
A

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 3. Materials and Methods

Synthesis procedure of Benzimidazole :

A mixture of aldehyde (20 mmol), o-phenylenediamine (20 mmol), boric

acid (1 gm) (Catalyst) and water (10 mL) was stirred at room temperature for the

appropriate time indicated in the following table. The progress of reactions was

monitored by TLC (ethyl acetate/petroleum ether). After completion of the reaction,

water (5 mL) was added and the mixture was stirred for 10- 30 min. The obtained solid

was collected by filtration and purified by recrystallization from ethanol.

All benzimidazole derivatives are synthesized by this method.

Aromatic Aldehydes used for the synthesis-

1) 4-Chlorobenzaldehyde

2) 2-Hydroxybenzaldehyde (Salicyladehyde)

3) 4-Hydroxybenzaldehyde

4) 3- Methoxy- 4- Hydroxybenzaldehyde (Vaniline)

5) 4-Nitrobenzaldehyde

6) 3, 4-Dimethoxybenzaldehyde

General Reacion-

NH2 R
N
H Boric acid (1 gm)
Water (10 ml)
Stirring N
R NH2 H

Aryl Aldehyde o- Phenylene diamine Benzimidazole derivative

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 4. Results & Discussion
%
Sr. No. Aldehyde Catalyst Time Product Practical
Yield

CHO N

1. Boric acid Cl
10 min. 95 %
(1 gm) N
H
Cl
2-(4-chlorophenyl)-1H-benzoimidazole
4- Chlorobenzaldehyde

HO
CHO
N
2. Boric acid
15 min. 93 %
(1 gm)
OH N
H
2- Hydroxybenzaldehyde
2-(2-hydroxyphenyl)-1H-benzoimidazole

CHO N

3. Boric acid OH
15 min. 92 %
(1 gm) N
H
HO
2-(4-hydroxyphenyl)-1H-benzoimidazole
4- Hydroxybenzaldehyde

O
MeO CHO
N

4. Boric acid OH
10 min. 93 %
HO (1 gm) N
H
3- Methoxy- 4- Hydroxy 2-(3-methoxy-4-hydroxyphenyl)-1H-benzoimidazole
benzaldehyde

N
CHO
NO2
5. Boric acid
20 min. N 90 %
(1 gm) H
O2N
2-(4-nitrophenyl)-1H-benzoimidazole
4-Nitrobenzaldehyde

H3CO CHO OCH3

N
6. Boric acid
10 min. OCH3 94 %
H3CO
(1 gm)
N
H
3,4- Dimethoxybenzaldehyde
2-(3,4-dimethoxyphenyl)-1H-benzoimidazole

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 Discussion -

Boric acid catalysed synthesis of benzimidazoles by stirring of

mixture of aryl amine (o- Phenylenediamine) and substituted aryl

aldehyde at room temperature. o- Phenylenediamine is electron

donating group (activator of benzene ring) and it is observed that the

reaction between aromatic aldehyde and aromatic amine leading to

the formation of benzimidazole should be very fast i. e. reaction

time required for the completion is very short and product yield is

higher by the use of catalyst.

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 5. THIN LAYER CHROMATOGRAPHIC DATA

Sr.
Name of the product TLC Product
No.
N

Cl

N
H
2-(4-chlorophenyl)-1H-benzoimidazole

1 Rf Reactant = 0.48
Rf Product = 0.66
Solvent = Ethyl acetate + Petroleum
ether (1:4)
M. P. = 261oC
HO

N
H
2-(2-hydroxyphenyl)-1H-benzoimidazole
2
Rf Reactant = 0.62
Rf Product = 0.58
Solvent = Ethyl acetate + Petroleum
ether (1:4)
M. P. = 113oC
N

OH

N
H

2-(4-hydroxyphenyl)-1H-benzoimidazole

3 Rf Reactant = 0.43
Rf Product = 0.32
Solvent = Ethyl acetate + Petroleum
ether (1:4)
M. P. = 198oC

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Sr.
Name of the product TLC Product
No.
O

OH

N
H
2-(3-methoxy-4-hydroxyphenyl)-1H-benzoimidazole

4 Rf Reactant = 0.71
Rf Product = 0.66
Solvent = Ethyl acetate + Petroleum
ether (2:8)
M. P. = 229oC
N

NO2

N
H
2-(4-nitrophenyl)-1H-benzoimidazole

5 Rf Reactant = 0.72
Rf Product = 0.43
Solvent = Ethyl acetate + Petroleum
ether (1:4)
M. P. = 201oC
OCH3

OCH3

N
H
2-(3,4-dimethoxyphenyl)-1H-benzoimidazole

6 Rf Reactant = 0.38
Rf Product = 0.46
Solvent = Ethyl acetate + Petroleum
ether (1:4)
M. P. = 166oC

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 6. Spectroscopic Identification (IR)
1) 4- Chlorobenzaldehyde to 2-(4-chlorophenyl)-1H-
benzoimidazole
N

Cl

N
H
2-(4-chlorophenyl)-1H-benzoimidazole

IR Spectra-
103
102
Transmittance [%]
100 99
98 101

3741.96
3674.34
3665.45
3615.09
3552.43

3250.55

2924.79
2855.42

2380.95
2311.71

1746.32
1701.10
1670.42
1620.92
1593.34
1523.70
1442.05
1424.45
1392.27
1314.37
1269.52
1185.43
1085.44
1008.38
958.75

821.96
736.21

3500 3000 2500 2000 1500 1000

Wavenumber cm-1

C:\Program Files\OPUS_65\MEAS\NKP 1.0 NKP 1 Solid 01/01/2003

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IR Data shows following major values-

1) Amine N-H = 3552 – 3741 cm-1
2) Ar. Amine Ar-N-H = 1185 – 1332 cm-1
3) Imine C=N = 1620 – 1670 cm-1
4) Aromatic ring Ar = 1523 – 1593 cm-1
5) Ar- Chlorine Ar- Cl = 736 – 821 cm-1
6) Ar- Hydrogen Ar-C-H = 2855 – 2924 cm-1
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 2) 2- Hydroxybenzaldehyde to 2-(2-hydroxyphenyl)-1H-
benzoimidazole
HO

N
H
2-(2-hydroxyphenyl)-1H-benzoimidazole

IR Spectra-
101
100
Transmittance [%]
97 98 96
95 99

3891.98
3858.71
3824.67
3740.68
3675.39
3617.41

2925.38
2853.29

2379.95
2312.08

1748.35
1702.71
1606.02
1553.55
1524.91
1475.87
1450.73
1394.01
1270.89
1184.63
1144.63
1092.85
1007.54
969.67
902.27
821.62
747.68

3500 3000 2500 2000 1500 1000

Wavenumber cm-1

C:\Program Files\OPUS_65\MEAS\NKP 2.0 NKP 2 Solid 01/01/2003

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IR Data shows following major values-

1) Amine N-H = 3740 – 3891 cm-1
2) Ar. Amine Ar-N-H = 1092 – 1270 cm-1
3) Imine C=N = 1606 – 1748 cm-1
4) Hydroxy O-H = 3617 – 3675 cm-1
5) Ar- Hydroxy Ar- OH = 1006 – 1065 cm-1
6) Ar- Hydrogen Ar-C-H = 2853 – 2925 cm-1
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 3) 4- Hydroxybenzaldehyde to 2-(4-hydroxyphenyl)-1H-
benzoimidazole
N

OH

N
H

2-(4-hydroxyphenyl)-1H-benzoimidazole

IR Spectra-
102
100
Transmittance [%]
96 94
92 98

3858.06
3824.03
3742.66
3665.64
3616.41

3393.43

2379.50
2313.38

1747.07
1701.38

1593.73
1543.45
1512.25
1482.44
1446.79

1264.12
1236.02
1156.76
1101.24

957.60
874.65
831.41
802.15
734.11

3500 3000 2500 2000 1500 1000

Wavenumber cm-1

C:\Program Files\OPUS_65\MEAS\NKP 3.0 NKP 3 Solid 01/01/2003

Page 1/1

IR Data shows following major values-

1) Amine N-H = 3742 – 3868 cm-1
2) Ar. Amine Ar-N-H = 1101 – 1264 cm-1
3) Imine C=N = 1543 – 1593 cm-1
4) Hydroxy O-H = 3616 – 3665 cm-1
5) Ar- Hydroxy Ar- OH = 1101 – 1264 cm-1
6) Ar- Hydrogen Ar-C-H = 2853 – 2925 cm-1

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 7. Conclusion

The method describes a convenient and efficient process for the

synthesis of 2-substitued benzimidazoles by one-pot reaction of o-

phenylenediamine with aldehydes in the presence of catalyst boric acid in

water at room temperature. This method offers some advantages in terms of

simplicity of performance, using water as solvent, low reaction times, low

cost and it follows along the line of green chemistry. The catalyst is readily

available and inexpensive and can conveniently be handled and removed

from the reaction mixture. We believe that this procedure is convenient,

economic and a user-friendly process for the synthesis of substituted

imidazoles of biological and medicinal importance.

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 8. References

1. Denny W A, Rewcastle G W and Baguley B C, J Med Chem., 1990, 33(2), 814-819.

2. Fonseca T, Gigante B and Gilchrist T L, Tetrahedron, 2001, 57, 1793-1799.

3. Kohara Y, Kubo K, Imamiya E, Wada T, Inada Y and Naka T, J Med Chem., 1996,

39, 5228-5235.

4. Porcari A R, Devivar R V, Kucera L S, Drach J C and Townsend L B, J Med Chem.,

1998, 41(8), 1252-1262.

5. Zarrinmayeh H, Zimmerman D M, Cantrell B E, Schober D A and Bruns R F, Bioorg

Med Chem Lett., 1999, 9(5), 647-652.

6. Hasegawa E, Yoneoka A, Suzuki K. Kato T, Kitazume T and Yangi K, Tetrahedron,

1999, 55, 12957-12968.

7. Katritzky A R and Boulton A J, Advances in Heterocyclic Chemistry; Vol. 27;

Academic: New York, 1980, 27, 241.

8. Preston P N, Weissberger A and Taylor E C, Chemistry of Heterocyclic Compounds;

Part 1, Wiley: New York, 1981, 40, 6-60.

9. Kartritzky A R and Rees C W, Comprehensive Heterocyclic Chemistry; Pergamon:

Oxford, 1984, 5, 457-474.

10. Benincori T and Sannicolo F, J Heterocycl Chem., 1988, 25, 1029-1033.

11. Trivedi R, De S K and Gibbs R A, J Mol Cat A Chem., 2006, 245, 8-11.

12. Gogoi P and Konwar D, Tetrahedron Lett., 2006, 47(1), 79-82.

13. Chakrabarty M, Karmakar S, Mukherjee R, Arima S and Harigaya Y, Monatsh

Chem., 2009, 140, 375-380.

14. Mukhopadhyay C and Tapaswi P K, Tetrahedron Lett., 2008, 49, 6237-6240.

15. Das B, Holla H and Srinivas Y, Tetrahedron Lett., 2007, 48, 61-64.

20 | P a g e
16. Sharghi H, Asemani O and Khalifeh R, Synth Commun., 2008, 38, 1128-1136.

17. Lindstrom U M, Organic Reactions in Water; Blackwell Publishing: Oxford, 2007.

18. Karimi-Jaberi Z and Arjmandi R, Monatsh Chem., 2011, 142, 631-635.

19. Karimi-Jaberi Z, Amiri M and Sadeghi N, Synth Commun., 2010, 40, 2948-2953.

20. Karimi-Jaberi Z, Abbasi S Z, Pooladian B and Jokar M, E-J Chem., 2011, 8(4), 1895-

1899.

21. Chaudhuri M K, Hussain S, Kantam M L and Neelima B, Tetrahedron Lett., 2005, 46,

8329-8331.

22. Tu S, Fang F, Miao C, Jiang H, Feng Y, Shi D and Wang X, Tetrahedron Lett., 2003,

44, 6153-6155.

23. Kondaiah G C M, Reddy L A, Babu K S, Gurav V M, Huge K G, Bandichhor R,

Reddy P P, Bhattacharya A and Anand R V, Tetrahedron Lett., 2008, 49, 106-109.

24. Mukhopadhyay C, Datta A and Butcher R J, Tetrahedron Lett., 2009, 50, 4246-4250.

25. Karimi-Jaberi Z and Amiri M, Hetroatom Chem., 2010, 21, 96-98.

26. Karimi-Jaberi Z and Keshavarzi M, Chin Chem Lett., 2010, 21, 547-549

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