Catalysis by FeF3 in water: a green synthesis of 2-substituted 1,3-benzazoles and 1,2-disubstituted benzimidazoles

Registered Charity Number 207890

Accepted Manuscript

This is an Accepted Manuscript, which has been through the RSC Publishing peer review process and has been accepted for publication.

Accepted Manuscripts are published online shortly after acceptance, which is prior to technical editing, formatting and proof reading. This free service from RSC Publishing allows authors to make their results available to the community, in citable form, before publication of the edited article. This Accepted Manuscript will be replaced by the edited and formatted Advance Article as soon as this is available.

To cite this manuscript please use its permanent Digital Object Identifier (DOI®), which is identical for all formats of publication.

More information about Accepted Manuscripts can be found in the Information for Authors.

Please note that technical editing may introduce minor changes to the text and/or graphics contained in the manuscript submitted by the author(s) which may alter content, and that the standard Terms & Conditions and the ethical guidelines that apply to the journal are still applicable. In no event shall the RSC be held responsible for any errors or omissions in these Accepted Manuscript manuscripts or any consequences arising from the use of any information contained in them.

www.rsc.org/advances

RSC AdvancesD

ownl

oade

d on

28

Sept

embe

r 20

12Pu

blis

hed

on 2

7 Se

ptem

ber

2012

on

http

://pu

bs.r

sc.o

rg |

doi:1

0.10

39/C

2RA

2230

2CView Online / Journal Homepage

http://www.rsc.org/Publishing/Journals/guidelines/AuthorGuidelines/JournalPolicy/accepted_manuscripts.asp

http://www.rsc.org/help/termsconditions.asp

http://www.rsc.org/Publishing/Journals/guidelines/EthicalGuidelines/index.asp

http://dx.doi.org/10.1039/c2ra22302c

http://pubs.rsc.org/en/journals/journal/RA

RSC Advances

Cite this: DOI: 10.1039/c0xx00000x

www.rsc.org/advances

Dynamic Article Links ►

PAPER

This journal is © The Royal Society of Chemistry [year] RSC Adv, 2012, 2, 00–00 | 1

Catalysis by FeF3 in water: A green synthesis of 2-substituted 1,3-

benzazoles and 1,2-disubstituted benzimidazoles

T. Bhaskar Kumar,a,b Ch. Sumanth,

a A. V. Dhanunjaya Rao,

a Dipak Kalita,

a M. Srinivasa Rao,

a K. B.

Chandra Sekhar,b K. Shiva Kumar,

c Manojit Pal

c,*

Received (in XXX, XXX) Xth XXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX 5

DOI: 10.1039/b000000x

FeF3 in water facilitated the reaction of 1,2-phenylenediamine / 2-aminothiophenol with 1 equivalent of alkyl/aryl aldehydes leading to

1,3-benzazoles under open air. The process afforded 1,2-disubstituted benzimidazoles when 1,2-phenylenediamine was reacted with 2

equivalent of aryl aldehydes. The methodology is operationally simple, free from the use of hazardous organic solvent and

chemoselective. The products were isolated by simple filtration and the catalyst can be recovered and recycled. 10

Introduction

Development of atom-efficient chemical process using

environmentally benign chemistry that minimizes or

eliminates the formation of by products has become a frontier 15

area of research in modern organic synthesis.1 Thus a number

of transition metal catalysts has been developed that enabled

chemical synthesis to proceed by simple addition reactions.1e

As an important class of heterocyclic compounds, 1,3-

benzazoles (A, Figure 1) i.e. benzimidazole and benzothiazole 20

are considered as privileged structures in the area of medicinal

chemistry.2 This is exemplified by a range of commonly used

drugs such as proton-pump inhibitor Omeprazole (B), TTX-

sensitive sodium channels blocker Riluzole (C), H1 receptor

antagonist Mizolastin (D), AT1 receptor antagonists 25

Telmisartan (E) and direct thrombin inhibitor Dabigatran

(Figure 1).

The most commonly used synthetic methods for accessing

benzimidazole derivatives include condensation of 1,2-

phenylenediamines with (i) carboxylic acids3,4 or their 30

derivatives5 or (ii) aldehydes followed by oxidative

cyclodehydrogenation.6,7 Similarly, 2-substituted

benzothiazoles can be synthesized8 via condensation of 2-

aminothiophenol with (i) carboxylic acids9 followed by

dehydration or (ii) aldehydes under oxidative conditions.10 35

While many of these methods are quite effective and useful

most of them however, suffer from the use of acidic or similar

reagents or hazardous organic solvents that are not

-------------------------------------------------------------------------- aCustom Pharmaceutical Services, Dr. Reddy’s Laboratories Limited, 40

Bollaram Road Miyapur, Hyderabad 500 049, India bDepartment of Chemistry, Institute of Science and Technology, JNT

University, Anantapur 515002, Andhra Pradesh, India cInstitute of Life Sciences, University of Hyderabad Campus, Gachibowli,

Hyderabad, 500046, India. 45

E-mail: [email protected]

†Electronic Supplementary Information (ESI) available: Copies of NMR

spectra for all new compounds. For ESI See DOI: 10.1039/b000000x/

50

X

N

1

2

345

6

7

1,3-Benzazoles (A)(X = NH; benzimidazole,

= S; benzothiazole)

NH

N

S

O

N

H3CO

Omeprazole (B)

S

N

NH2

F3CO

Riluzole (C)

N

N

N

F

N

N

NHO

Mizolastin(D)

N

N

N

N

HO

O

Telmisartan (E)

Figure 1. Examples of 1,3-benzazole based drugs.

environmentally compatible and produce a large amount of 55

waste. Moreover, the requirement of longer reaction time,

higher temperature and expensive reagents/catalysts are the

other drawbacks of these methodologies. In some of these

cases the formation of side products e.g. 1,2-disubstituted

benzimidazole along with the desired 2-substituted derivative 60

was also observed.

During last several years the iron salts have been reported as

promising and alternative transition-metal catalysts that

received much attention due to their low price, sustainability,

ready availability, nontoxicity, and environmental friendly 65

properties.11 More recently, in addition to its commercial use

in the production of ceramics FeF3 has also received attention

in organic synthesis.12 These include its use in chemoselective

addition of cyanide to aldehydes, synthesis of

Page 1 of 12 RSC Advances

RS

C A

dva

nce

s A

ccep

ted

Man

usc

rip

t

Dow

nloa

ded

on 2

8 Se

ptem

ber

2012

Publ

ishe

d on

27

Sept

embe

r 20

12 o

n ht

tp://

pubs

.rsc

.org

| do

i:10.

1039

/C2R

A22

302C

View Online


2 | RSC Adv. 2012, 2, 00–00 This journal is © The Royal Society of Chemistry [year]

polyhydroquinolines, direct thiolation of an arene C-H bond

etc. Additionally, the use of water as an inexpensive and

environmental friendly solvent in commercially available and

water stable FeF3 catalyzed reaction has also been explored.12a

This is remarkable as the use of large volumes of volatile 5

hazardous organic solvents in industrial processes posed a

serious threat to the environment. Thus, procedures involving

alternative benign solvents in reaction, isolation and

purification are of high priority in industry. These prompted

us to develop a green and atom-efficient one-pot synthesis of 10

1,3-benzazoles (benzimidazole and benzothiazole) via FeF3

catalyzed reaction in water. Herein we report our preliminary

findings on FeF3–mediated condensation of 1,2-

phenylenediamine / 2-aminothiophenol (1) with 1.0 equivalent

of alkyl/aryl aldehydes (2) leading to 1,3-benzazoles (3) in 15

open air (Scheme 1). The synthesis of 1,2-disubstituted

benzimidazoles is also presented.

NH2

XH

+ R2OHCX

N

R2FeF3

H2O, heat

air

R

R1

R

R1

1 2 3X = NH, S

20

Scheme 1. FeF3 catalyzed synthesis of 1,3-benzazoles in water.

Results and discussion

Initially, we examined the reaction of 1,2-phenylenediamine

(1a) with p-chloro benzaldehyde (2a) in the presence of 25

FeCl3 in water at 60 oC for 7 h when the desired

benzimidazole (3a) was isolated in 75% yield (entry 1, Table

1). While the yield of 3a was increased when FeCl3.6H2O was

used in place of FeCl3 (entry 2, Table 1) the maximum yield

however was achieved using FeF3 (entry 3, Table 1) indicating 30

its most suitability for the present reaction. The use of other

catalysts e.g. NH4F and TBAF was examined but found to be

less effective (entries 4-5, Table 1). The yield of 3a was

decreased when the reaction was carried out at lower

temperature (entry 6, Table 1). The use of other solvents was 35

also examined (entries 7-8, Table 1) among which 1,4-dioxane

EtOH and MeOH was found to be effective. Nevertheless,

being inexpensive and readily available green solvent water

was chosen for further study on the present FeF3 mediated

condensation reaction. To test the recyclability of the catalyst 40

used FeF3 was recovered by simple filtration and reused in the

same reaction when 3a was isolated without significant loss of

its yield. The yield of 3a was found to be 83, 81 and 78 after

1st, 2nd and 3rd recovery and reuse of the catalyst. A

comparison of the XRD spectrum obtained for fresh FeF3 and 45

the reused catalyst indicated no change in their crystalline

nature (Fig. 2). Notably, all these reactions were carried out in

open air and therefore free from the use of inert/anhydrous

atmosphere thereby avoiding possible pressure development

in a closed reaction vessel especially in scale-up synthesis. 50

Overall, the combination of FeF3 in water was found to be

optimal for the preparation of 3a.

Table 1. The effect of reaction conditions on condensation of 1a with 2a.a

NH2

NH2

OHC ClN

HN

Cl

1a 2a 3a

Catalyst

Solventheat, air

+

Entry Catalyst (mmol) Solvent T °C; t (h)

Yield (%)b

1 FeCl3 (0.05) H2O 60; 7 75 2 FeCl3.6H2O (0.05) H2O 60; 7 81

3 FeF3 (0.02) H2O 60; 7 85 (83, 81, 78)c

4 NH4F (0.02) H2O 60; 7 50 5 TBAF (0.02) H2O 60; 7 65

6 FeF3 (0.02) H2O 25; 7 78

7 FeF3 (0.02) Toluene 110; 12 73 8 FeF3 (0.02) 1,4-Dioxane 100; 8 80

9 FeF3 (0.02) MeOH 65; 2 83

10 FeF3 (0.02) EtOH 80; 2 85

aAll the reactions were carried out by using 1,2-phenylenediamine 1a (1.0 55

mmol), aldehyde 2a (1.0 mmol), a catalyst (0.02 mmol) in a solvent (5

mL) in open air. bIsolated yields. cCatalyst was reused for additional three runs and figures within parentheses indicate the corresponding yield for

each run.

60

Fig. 2. XRD spectrum of fresh FeF3 and the reused catalyst after first

cycle.

Having the optimized reaction conditions in hand we then

examined the generality and scope of the present FeF3 65

mediated reaction in water. Thus, a range of aldehydes (2)

was initially reacted with 1a and the results are summarized in

Table 2. Various electron donating groups e.g. Cl, Br, Me, tBu

and NMe2 (entries 1-5, Table 2) or electron withdrawing

groups e.g. CF3 and COOH (entry 6 and 7, Table 2) present on 70

the aryl ring of aldehydes were well tolerated. The use of

heteroaromatic (entries 8 and 9, Table 2) and aliphatic

aldehydes (entry 10, Table 2) were also successful and

afforded the desired 2-substituted benzimidazoles in good

yields. The reaction proceeded smoothly with other 1,2-75

phenylenediamines e.g. 1b-d as well (entries 11-14, Table 2),

Page 2 of 12RSC Advances

RS

C A

dva

nce

s A

ccep

ted

Man

usc

rip

t

Dow

nloa

ded

on 2

8 Se

ptem

ber

2012

Publ

ishe

d on

27

Sept

embe

r 20

12 o

n ht

tp://

pubs

.rsc

.org

| do

i:10.

1039

/C2R

A22

302C

View Online


This journal is © The Royal Society of Chemistry [year] RSC Adv., 2012, 2, 00–00 | 3

Table 2. FeF3 catalyzed synthesis of 2-substituted benzimidazoles/benzothiazoles in water (Scheme 1).a

Entry

o-phenylenedi amines /

o-aminobenzenethiol (1) Aldehyde (2) Products (3)b Yield (%)c

1

NH2

NH2 1a

OHC Cl

2a

NH

NCl

3a

85

2

1a

OHC Br

2b

NH

NBr

3b

86

3

1a

OHC

2c

NH

N

3c

88

4 1a

OHC

2d

NH

N

3d

80

5 1a OHC N

2e

NH

NN

3e

81

6

1a

OHC CF3

2f

NH

NCF3

3f

83

7 1a

OHC CO2H

2g

NH

NCOOH

3g

88


RS

C A

dva

nce

s A

ccep

ted

Man

usc

rip

t

Dow

nloa

ded

on 2

8 Se

ptem

ber

2012

Publ

ishe

d on

27

Sept

embe

r 20

12 o

n ht

tp://

pubs

.rsc

.org

| do

i:10.

1039

/C2R

A22

302C

View Online



8

1a OOHC

2h

NH

N

O

3h

89

9

1a SOHC

2i

NH

N

S

3i

90

10

1a

OHC

2j

NH

N

3j

90

11

NH2

NH2 1b

2b

NH

N

Br

3k

84

12 1b 2g NH

NCO2H

3l

78

13

Cl

NH2

NH2 1c

2c

NH

N

Cl

3m

80

14

O2N

NH2

NH2 1d

2b

NH

N

Br

O2N

3n

75

15

SH

NH2

1e

2g

S

NCO2H

3o

92d


RS

C A

dva

nce

s A

ccep

ted

Man

usc

rip

t

Dow

nloa

ded

on 2

8 Se

ptem

ber

2012

Publ

ishe

d on

27

Sept

embe

r 20

12 o

n ht

tp://

pubs

.rsc

.org

| do

i:10.

1039

/C2R

A22

302C

View Online



16 1e

OHC

O2N

2k

S

N

O2N

3p

92d

17 1e OHC CN

2l

S

NCN

3q

90d

18 1a OHC

2m

NH

N

3r

85

19 1a OHC

2n

NH

N

3s

81

20 1a OHC

2o

NH

N

3t

79

aAll the reactions were carried out by using 1,2-phenylenediamines/ 2-aminobenzenethiol 1 (1.0 mmol), aldehyde 2 (1.0 mmol), FeF3 (0.02 mmol) in water (5 mL) at 60 °C for 7-8 h in open air. bIdentified by 1H NMR, IR and MS. cIsolated yields. dThe reaction was carried out using 1.2 mmol of

aldehyde.

5

10

15

Table 3. FeF3 catalyzed synthesis of 1,2-disubstituted benzimidazoles in watera

NH2

NH2

+ R2OHCN

N

R2

R1

R1

1 2 4

R R

R2

2

FeF3

H2O, heat

air


RS

C A

dva

nce

s A

ccep

ted

Man

usc

rip

t

Dow

nloa

ded

on 2

8 Se

ptem

ber

2012

Publ

ishe

d on

27

Sept

embe

r 20

12 o

n ht

tp://

pubs

.rsc

.org

| do

i:10.

1039

/C2R

A22

302C

View Online



Entry

o-phenylenedi

amine (1) Aldehyde (2) Product (4)b Yield (%)c

1

NH2

NH2 1a

OHC OH

2m

N

NOH

OH

4a

85

2

1a

OHC OH

OH

2n

N

NOH

OH

OH

OH

4b

80

3

1b

2c

N

N

4c

78

4 NH2

NH2

Cl

Cl

1f

2c

N

N

Cl

Cl 4d

77

5 1a NOHC

2o

N

N

N

N

4e

80

6 1a NH

CHO

2p N

N

HN

NH

4f

73

aAll the reactions were carried out by using 1,2-phenylenediamines 1 (1.0 mmol), aldehyde 2 (2.0 mmol), FeF3 (0.02 mmol) in water (5 mL) at 60 °C for

10 h in open air. bIdentified by 1H NMR, IR and MS. cIsolated yields.


RS

C A

dva

nce

s A

ccep

ted

Man

usc

rip

t

Dow

nloa

ded

on 2

8 Se

ptem

ber

2012

Publ

ishe

d on

27

Sept

embe

r 20

12 o

n ht

tp://

pubs

.rsc

.org

| do

i:10.

1039

/C2R

A22

302C

View Online



To extend the scope of this methodology further we examined

the use of 2-aminothiophenol (1b) in place of 1a and the

corresponding 2-aryl substituted benzothiazoles were obtained

in good yields (entries 15–17, Table 2). Furthermore, present 5

metod afforded 2-alkyl benzimidazoles in good yields (entries

18-20, Table 2) the preparation of which was not very

convenient earlier as most of the reported methods were either

less effective or ineffective in terms of products yield.

Prompted by the fact that 1,2-disubstituted benzimidazoles 10

can be accessed by direct one-step condensation of 1,2-

phenylenediamines with aryl aldehydes13 we decided to

explore the potential of the present FeF3 catalyzed reaction in

the synthesis of these compounds in a single pot. Accordingly,

2.0 equiv of aldehyde was reacted with 1.0 equiv of 1,2-15

phenylenediamines under the condition as mentioned earlier

(entry 3, Table 1). To our satisfaction the reaction proceeded

smoothly to give the desired 1,2-disubstituted benzimidazoles

(4) in good yields (Table 3). Thus, the present methodology

can be used to prepare mono or di substituted derivatives 20

depending on the conditions employed. The experimental

procedure is simple and the product can be isolated by

filtration followed by purification through crystallization.

Mechanistically, the reaction seems to proceed via a sequence

(Scheme 2) involving the FeF3 promoted formation of Shiff 25

base of type E-2 (via the intermediate E-1) followed by

intramolecular ring closure leading to E-3. The oxidative

dehydrogenation of E-3 by air affords the desired product 3.

In the presence of 2.0 equivalent of aldehyde the diamine (1a-

b and 1f) undergoes FeF3-mediated formation of Shiff base E-30

4 [i.e. N1,N2-bis(arylidene)benzene-1,2-diamine] which on

intramolecular cyclization followed by 1,3-hydride migration

affords the 1,2-disubstituted benzimidazole 4 (Scheme 3).13

While air seems to have no role in this case its presence

however did not affect the reaction. 35

NH2

XH

+X

N

R2

1 2 3X = NH, S

N

XH

E-2

R2

R2

O

H

FeF3

N

XH

E-1

O

R2

H

FeF3H

-H2O

-FeF3

F3Fe

X

HN R2

H

O2 (air)

E-3

Scheme 2. Proposed mechanism for the fomation of 1,3-

benzazoles (3)

40

Conclusions

In conclusion, a green, efficient and simple method has been

developed for the facile and one-pot synthesis of 2-substituted

benzimidazoles / benzothiazoles and 1,2-disubstituted

benzimidazoles. The methodology involved catalysis by FeF3 45

in water that facilitated the reaction of 1,2-phenylenediamine /

2-aminothiophenol with 1 equivalent of alkyl/aryl aldehydes

NH2

NH2

+N

N

R2

1a-b & 1f2 4

R2

O

H

FeF3

N

N

R2

R2

FeF3

N

N R2

FeF3

R2

H

R2

E-4E-5

-FeF3

Scheme 3. Proposed mechanism for the fomation of 1,2-disubstituted 50

benzimidazole (4)

leading to 1,3-benzazoles under open air. The process

afforded 1,2-disubstituted benzimidazoles when 1,2-

phenylenediamine was reacted with 2 equivalent of aryl 55

aldehydes. The products were isolated by simple filtration and

the catalyst can be recovered and recycled. The operational

simplicity, excellent yields of the products, and high

chemoselectivity are the main advantages of this method, and

furthermore, this procedure is inexpensive, safer and 60

environmentally benign. The present example of first FeF3

mediated synthesis of 1,3-benzazoles / 1,2-disubstituted

benzimidazoles therefore would find wide applications.

Experimental section 65

General methods: Unless stated otherwise, reactions were

performed under nitrogen atmosphere using oven dried

glassware. Reactions were monitored by thin layer

chromatography (TLC) on silica gel plates (60 F254),

visualizing with ultraviolet light or iodine spray. Flash 70

chromatography was performed on silica gel (230-400 mesh)

using distilled hexane, ethyl acetate, dichloromethane. 1H

NMR and 13C NMR spectra were determined in DMSO-d6

solution by using 400 or 100 MHz spectrometers,

respectively. Proton chemical shifts (δ) are relative to 75

tetramethylsilane (TMS, δ = 0.00) as internal standard and

expressed in ppm. Spin multiplicities are given as s (singlet),

d (doublet), t (triplet) and m (multiplet) as well as b (broad).

Coupling constants (J) are given in hertz. Infrared spectra

were recorded on a FT-IR spectrometer. Melting points were 80

determined using melting point B-540 apparatus and are

uncorrected. MS spectra were obtained on a mass

spectrometer. HRMS was determined using waters LCT

premier XETOF ARE-047 apparatus. The catalyst FeF3 (light


RS

C A

dva

nce

s A

ccep

ted

Man

usc

rip

t

Dow

nloa

ded

on 2

8 Se

ptem

ber

2012

Publ

ishe

d on

27

Sept

embe

r 20

12 o

n ht

tp://

pubs

.rsc

.org

| do

i:10.

1039

/C2R

A22

302C

View Online



green color powder; purity 98%; CAS No: 7783-50-8) used is

commercially available.

General procedure for the preparation of compound 3a-t

A mixture of 1,2-phenylenediamine/ 2-aminobenzenethiol 1 (1 5

mmol), adehyde 2 (1 mmol for the preparation of

benzoimidazole, 1.2 mmol for the preparation of

benzothiazoles), FeF3 (0.02 mmol), and water (5 mL) was

heated at 50-60 °C for 7-8 h. After completion of the reaction

(indicated by TLC), the mixture was cooled to room 10

temperature and filtered. The solid obtained was treated with

cold water (10 mL) and filter under vacuum. The crude

product was recrystallized from ethanol to afford the desired

product.

15

2-(4-Chlorophenyl)-1H-benzo[d]imidazole (3a)

White solid; mp 291-292 °C (lit14 290-292 °C); 1H NMR

(DMSO-d6, 400 MHz): δ 12.99 (bs, 1H), 8.19 (d, J = 8.0 Hz,

2H), 7.65 (q, J = 8.0 Hz, 3H), 7.54 (d, J = 8.0 Hz, 1H), 7.21

(t, J = 8.0 Hz, 2H); 13C NMR (DMSO-d6, 100 MHz): δ 150.1, 20

143.7, 135.0, 134.4, 129.0 (3C), 128.1 (2C), 122.7, 121.9,

118.9, 111.4; IR (KBr): 3051, 1586, 1490, 1448, 1429, 1272,

831, 745, 728 cm-1; HRMS (ESI): calcd for C13H10N2Cl

(M+H)+ 229.0533, found 229.0525; MS (ESI): m/z ([M+H]+):

229.1 25

2-(4-Bromophenyl)-1H-benzo[d]imidazole (3b)

White solid; mp 295-296 °C (lit6c 291–294 °C); 1H NMR

(DMSO-d6, 400 MHz) δ 13.02 (br s, 1H), 8.13-8.11 (m, 2H),

7.77 (d, J = 6.80 Hz, 2H), 7.66 (d, J = 8.0 Hz, 1H), 7.53 (s, 30

1H), 7.23-7.18 (m, 2H); 13C NMR (DMSO-d6, 100 MHz): δ

150.0, 143.5, 134.7, 131.8 (2C), 129.0, 128.4 (2C), 123.1

(2C), 121.7, 118.7, 111.4; IR (KBr): 2846, 2745, 1447, 1427,

1274, 1011, 963, 828, 745 cm-1; HRMS (ESI): calcd for

C13H10N2Br (M+H)+ 273.0027, found 273.0033; MS (ESI): 35

m/z ([M+H]+): 273.1

2-(4-(Tert-butyl)phenyl)-1H-benzo[d]imidazole (3c)

White solid; mp 255-257 °C (lit15 250-251°C); 1H NMR

(DMSO-d6, 400 MHz) δ 12.82 (s, 1H), 8.10 (d, J = 8.0 Hz, 40

2H), 7.64 (d, J = 8.0 Hz, 1H), 7.57 (d, J = 8.0 Hz, 2H), 7.51

(d, J = 8.0 Hz, 1H), 7.22-7.15 (m, 2H), 1.33 (s, 9H); 13C NMR

(DMSO-d6, 100 MHz) δ 152.5, 151.3, 143.8, 134.9, 127.4,

126.2 (2C), 125.7 (2C), 122.3, 121.5, 118.7, 111.2, 34.5, 30.9

(3C); IR (KBr): 3696, 2959, 1431, 1269, 968, 840, 739 cm-1; 45

HRMS (ESI): calcd for C17H19N2 (M+H)+ 251.1548, found

251.1546; MS (ESI): m/z ([M+H]+): 251.3.

2-Mesityl-1H-benzo[d]imidazole (3d)

White solid; mp 252-254 °C (lit16 253-254 °C); 1H NMR 50

(DMSO-d6, 400 MHz): δ 12.4 (s, 1H), 7.61-7.58 (m, 2H),

7.20-7.17 (m, 2H), 7.00 (s, 2H), 2.31 (s, 3H), 2.06 (s, 6H); 13C

NMR (DMSO-d6, 100 MHz): δ 151.2, 138.3, 137.0 (2C),

128.7, 127.9 (3C), 121.4 (3C), 114.8 (2C), 20.8, 19.6 (2C); IR

(KBr): 3055, 2920, 2676, 1450, 1417, 1223, 851, 753 cm-1; 55

HRMS (ESI): calcd for C16H17N2 (M+H)+ 237.1392, found

237.1393; MS (ESI): m/z ([M+H]+): 237.2

4-(1H-Benzo[d]imidazol-2-yl)-N,N-dimethylaniline (3e)

Yellow solid; mp 285-286 °C (lit17 288-290 °C); 1H NMR 60

(DMSO-d6, 400 MHz): δ 12.5 (brs, 1H), 7.98 (d, J = 8.0 Hz,

2H), 7.67-7.51 (m, 2H), 7.14-7.08 (m, 2H), 6.82 (d, J = 8.0

Hz, 2H), 2.99 (s, 6H); 13C NMR (DMSO-d6, 100 MHz): δ

151.8, 150.7, 139.1 (2C), 127.3 (2C), 120.8 (2C), 116.7 (3C),

111.3 (2C), 39.1 (2C); IR (KBr): 3418, 3053, 1610, 1508, 65


C15H16N3 (M+H)+ 238.1344, found 238.1340; MS (ESI): m/z

([M+H]+): 238.2.

2-(4-(Trifluoromethyl)phenyl)-1H-benzo[d]imidazole (3f) 70

White solid; mp 262-264 °C (lit18 262-264 °C); 1H NMR

(DMSO-d6, 400 MHz) δ 13.17 (bs, 1H), 8.39 (d, J = 8.0 Hz,

2H), 7.94 (d, J = 8.0 Hz, 2H), 7.71 (d, J = 8.0 Hz, 1H), 7.57

(d, J = 8.0 Hz, 1H), 7.29-7.21 (m, 2H); 13C NMR (DMSO-d6,

100 MHz) δ 149.6, 143.7, 133.9, 129.6 (q, 1C, J = 32.1), 75

127.0 (4C), 125.9 (2C), 123.2, 122.0, 119.2, 111.6; IR (KBr):

3426, 1433, 1321, 1170, 1140, 1064, 850, 746 cm-1; HRMS

(ESI): calcd for C14H10N2F3 (M+H)+ 263.0796, found

263.0799; MS (ESI): m/z ([M+H]+): 263.1.

80

4-(1H-Benzo[d]imidazol-2-yl)benzoic acid (3g)

White solid, mp 327-329 °C; 1H NMR (DMSO-d6, 400 MHz):

δ 13.16 (bs, 1H), 13.02 (s, 1H), 8.20 (d, J = 8.0 Hz, 2H), 8.05

(d, J = 8.0 Hz, 2H), 7.73 (d, J = 8.0 Hz, 2H), 7.23-7.19 (m,

2H); 13C NMR (DMSO-d6, 100 MHz): δ 166.9, 150.1, 134.4, 85

133.9, 131.5, 129.9 (2C), 129.8, 129.6 (2C), 129.4, 129.2,

126.4 (2C); IR (KBr): 3061, 2925, 1708, 1387, 1289, 1116,

737 cm-1; HRMS (ESI): calcd for C14H11N2O2 (M+H)+

239.0821, found 239.0810; MS (ESI): m/z ([M+H]+): 239.1

90

2-(Furan-2-yl)-1H-benzo[d]imidazole (3h)

Light yellow solid; mp 285-287 °C (lit14 287–288 °C); 1H

NMR (DMSO-d6, 400 MHz): δ 12.9 (s, 1H), 7.94 (s, 1H), 7.55

(s, 2H), 7.21-7.19 (m, 3H), 6.73 (s, 1H); 13C NMR (DMSO-d6,

100 MHz): δ 145.5, 144.5 (3C), 143.6, 122.1 (2C), 112.2 95

(2C), 110.4 (2C); IR (KBr): 3059, 2661, 1630, 1525, 1417,


C11H9N2O (M+H)+ 185.0715, found 185.0708; MS (ESI): m/z

([M+H]+): 185.1

100

2-(Thiophen-2-yl)-1H-benzo[d]imidazole (3i)

Light yellow solid; mp 341-342 °C (lit14 341–343 °C); 1H

NMR (DMSO-d6, 400 MHz): δ 12.90 (brs, 1H), 7.83 (d, J =

8.0 Hz, 1H), 7.72 (d, J = 8.0 Hz, 1H), 7.56-7.54 (m, 2H),

7.24-7.18 (m, 3H); 13C NMR (DMSO-d6, 100 MHz): δ 147.0 105

(2C), 133.6, 128.7 (2C), 128.2 (2C), 126.6 (2C), 122.1 (2C);

IR (KBr): 3446, 1621, 1569, 1450, 1423, 1275, 1234, 1073,

944, 850, 742 cm-1; HRMS (ESI): calcd for C11H9N2S (M+H)+

201.0486, found 201.0481; MS (ESI): m/z ([M+H]+): 201.1 110

2-Cyclopropyl-1H-benzo[d]imidazole (3j)

White solid; mp 232- 234 °C (lit19 231-232 °C); 1H NMR

(DMSO-d6, 400 MHz): δ 12.10 (s, 1H), 7.40-7.38 (m, 2H),

7.08-7.06 (m, 2H), 2.11-2.08 (m, 1H), 1.05-1.01 (m, 4H); 13C 115

NMR (DMSO-d6, 100 MHz): δ 156.8, 121.0 (2C), 120.9 (2C),


RS

C A

dva

nce

s A

ccep

ted

Man

usc

rip

t

Dow

nloa

ded

on 2

8 Se

ptem

ber

2012

Publ

ishe

d on

27

Sept

embe

r 20

12 o

n ht

tp://

pubs

.rsc

.org

| do

i:10.

1039

/C2R

A22

302C

View Online



108.1 (2C), 9.3, 8.6 (2C); IR (KBr): 3474, 1632, 1420, 1263,

997, 749 cm-1; HRMS (ESI): calcd for C10H11N2 (M+H)+

159.0922, found 159.0916; MS (ESI): m/z ([M+H]+): 159.1

2-(4-Bromophenyl)-6-methyl-1H-benzo[d]imidazole (3k) 5

Light yellow solid; mp 242-243 °C; 1H NMR (DMSO-d6, 400

MHz) δ 12.84 (d, J = 16.0 Hz, 1H), 8.09 (d, J = 8.0 Hz, 2H),

7.75 (d, J = 8.0 Hz, 2H), 7.53 (d, J = 8.0 Hz, 1H), 7.48-7.31

(m, 1H), 7.06-7.01 (m, 1H), 2.43 (s, 3H); 13C NMR (DMSO-

d6, 100 MHz): δ 149.6, 132.1, 131.9 (3C), 129.5, 128.2 (2C), 10

124.2, 123.4, 122.9, 118.5, 111.1, 21.3; IR (KBr): 3440, 3200,

2919, 1631, 1416, 1316, 1011, 830, 714 cm-1; HRMS (ESI):

calcd for C14H12N2Br (M+H)+ 287.0184, found 287.0186; MS

(ESI): m/z ([M+H]+): 287.1

15

4-(5-Methyl-1H-benzo[d]imidazol-2-yl)benzoic acid (3l) Light brown solid; mp 281-282 °C; 1H NMR (DMSO-d6, 400

MHz): δ 13.15 (s, 1H), 13.02 (s, 1H), 8.21 (d, J = 8.0 Hz,

2H), 8.05 (d, J = 8.0 Hz, 2H), 7.71-7.69 (m, 1H), 7.56-7.54

(m, 1H), 7.23-7.21 (m, 1H), 2.33 (s, 3H); 13C NMR: Not 20

available due to poor solubility. IR (KBr): 3451, 1615, 1559,

1409, 868, 789, 715 cm-1; HRMS (ESI): calcd for C15H11N2O2

(M-H)+ 251.0821, found 251.0828; MS (ESI): m/z ([M+H]+):

251.2 25

2-(4-(Tert-butyl)phenyl)-6-chloro-1H-benzo[d]imidazole

(3m) White solid, mp 252-254 °C; 1H NMR (DMSO-d6, 400 MHz):

δ 13.03 (d, J = 8.0 Hz, 1H), 8.09 (d, J = 8.0 Hz, 2H), 7.70 (s,

1H), 7.58 (d, J = 8.0 Hz, 2H), 7.52 (d, J = 8.0 Hz, 1H), 7.21 30

(t, J = 8.0 Hz, 1H), 1.33 (s, 9H); 13C NMR (DMSO-d6, 100

MHz): δ 152.9 (2C), 126.9 (3C), 126.3 (4C), 125.7 (2C),

122.0 (2C), 34.6, 30.9 (3C); IR (KBr): 3696, 2961, 1616,

1422, 1308, 1061, 964, 846, 809, 710 cm-1; HRMS (ESI):

calcd for C17H18N2Cl (M+H)+ 285.1159, found 285.1155; MS 35

(ESI): m/z ([M+H]+): 285.2

2-(4-Bromophenyl)-5-nitro-1H-benzo[d]imidazole (3n)

Yellow solid; mp 176-177 °C (lit20 161–164 °C); 1H NMR

(DMSO-d6, 400 MHz) δ 13.69 (brs, 1H), 8.84 (s, 1H), 8.04 (d, 40

J = 8.0 Hz, 3H), 7.93 (d, J = 8.0 Hz, 1H), 7.73 (d, J = 8.0 Hz,

2H); 13C NMR (DMSO-d6, 100 MHz): δ 158.5, 151.1, 135.8,

135.2, 133.4, 132.1, 132.0, 131.6, 131.4, 130.9, 128.8, 128.4,

125.1, 124.4, 118.9, 113.0, 112.8, 101.7, 98.4; (Note: A

mixture of tautomers observed); IR (KBr): 3483, 3373, 1601, 45


C13H7N3O2Br (M-H)+ 315.9722, found 315.9729; MS (ESI):

m/z ([M+H]+): 317.1.

4-(Benzo[d]thiazol-2-yl)benzoic acid (3o) 50

Light yellow solid; mp 294-295 °C (lit21 294.1-295.5 °C); 1H

NMR (DMSO-d6, 400 MHz): δ 13.26 (br s, 1H), 8.23-8.20 (m,

3H), 8.18-8.10 (m, 3H), 7.60-7.56 (m, 1H), 7.51 (t, J = 8.0

Hz, 1H); 13C NMR (DMSO-d6, 100 MHz): δ 165.8, 153.2,

136.2, 134.5, 132.8, 130.0, 127.1, 126.6 (2C), 125.7, 123.0 55

(2C), 122.2 (2C); IR (KBr): 3058, 2827, 1681, 1609, 1427,

1293, 971, 860, 755 cm-1; HRMS (ESI): calcd for C14H10NO2S

(M+H)+ 256.0432, found 256.0428; MS (ESI): m/z ([M+H]+):

256.2

60

2-(2-Nitrophenyl)benzo[d]thiazole (3p)

Light green solid; mp 128-129°C (lit22 127-129 °C); 1H NMR

(DMSO, 400 MHz) δ 8.23 (d, J = 7.2 Hz, 1H), 8.09-7.99 (m,

3H,), 7.90-7.85 (m, 2H), 7.65-7.54 (m, 2H); 13C NMR

(DMSO-d6, 100 MHz): δ 162.2, 153.0, 148.4, 135.1, 133.0, 65

131.9, 131.7, 126.8, 126.2, 126.0, 124.5, 123.2, 122.4; IR

(KBr): 3083, 1608, 1536, 1367, 1305, 1231, 973, 761 cm-1;

HRMS (ESI): calcd for C13H9N2O2S (M+H)+ 257.0385, found

257.0387; MS (ESI): m/z ([M+H]+): 257.2.

70

4-(Benzo[d]thiazol-2-yl)benzonitrile (3q)

Greenish yellow solid; mp 171-173 °C (lit23 170.5-172.5 ºC); 1H NMR (DMSO-d6, 400 MHz) δ 8.28 (d, J = 8.0 Hz, 2H),

8.22 (d, J = 8.0 Hz, 1H), 8.13 (d, J = 8.0 Hz, 1H), 8.05 (d, J

= 8.0 Hz, 2H), 7.61 (t, J = 8.0 Hz, 1H), 7.53 (t, J = 8.0 Hz 75

1H); 13C NMR (DMSO-d6, 100 MHz): δ 165.0, 153.2, 136.4,

134.7, 133.1 (2C), 127.6 (2C), 126.8, 126.0, 123.2, 122.4,

118.1, 113.1; IR (KBr): 3422, 2227, 1480, 1315, 967, 839,

764 cm-1; HRMS (ESI): calcd for C14H9N2S (M+H)+

237.0486, found 237.0482; MS (ESI): m/z ([M+H]+): 237.1 80

2-Cyclohexyl-1H-benzo[d]imidazole (3r)

Colorless solid; mp 272- 273 °C (lit24 sublimes at 250 °C); 1H

NMR (DMSO-d6, 400 MHz): δ 12.13 (s, 1H), 7.50 (d, J = 8.0

Hz, 1H), 7.39 (d, J = 8.0 Hz, 1H), 7.12-7.06 (m, 2H), 2.82 (d, 85

J = 8.0 Hz, 1H), 2.03-1.98 (m, 2H), 1.82-1.78 (m, 2H), 1.72-

1.67 (m, 1H), 1.64-1.53 (m, 2H), 1.44-1.35 (m, 2H), 1.30-1.25

(m, 1H); MS (ESI): m/z ([M+H]+): 200.3

2-(Pentan-3-yl)-1H-benzo[d]imidazole25 (3s) 90

Off white solid; mp 262- 264 °C; 1H NMR (DMSO-d6, 400

MHz): δ 12.17 (s, 1H), 7.52 (d, J = 8.0 Hz, 1H), 7.40 (d, J =

8.0 Hz, 1H), 7.13-7.08 (m, 2H), 2.70 (d, J = 8.0 Hz, 1H),

1.79-1.72 (m, 4H), 0.77 (t, J = 8.0 Hz, 6H); MS (ESI): m/z

([M+H]+): 188.3 95

2-Ethyl-1H-benzo[d]imidazole26 (3t)

Light yellow solid; mp 159- 160 °C; 1H NMR (DMSO-d6, 400

MHz): δ 12.18 (bs, 1H), 7.42 (d, J = 8.0 Hz, 2H), 7.18 (d, J =

8.0 Hz, 2H), 2.81 (q, J = 8.0 Hz, 2H), 1.26 (t, J = 8.0 Hz, 100

3H); MS (ESI): m/z ([M+H]+): 146.2

General procedure for the preparation of compound 4a-4f

A mixture of 1,2-phenylenediamine 1 (1 mmol), adehyde 2 (2

mmol), FeF3 (0.02 mmol), and water (5 mL) was heated at 50-105

60 °C for 10 h. After completion of the reaction (indicated by

TLC), the mixture was cooled to room temperature and

filtered. The solid obtained was treated with cold water (10

mL) and filter under vacuum. The crude product was

recrystallized from ethanol to afford the pure product. 110

4-(1-(4-Hydroxybenzyl)-1H-benzo[d]imidazol-2-yl)phenol

(4a)

White solid; mp 254-256 °C; 1H NMR (DMSO-d6, 400 MHz):

δ 9.94 (bs, 1H), 9.38 (bs, 1H), 7.67 (d, J = 8.0 Hz, 1H), 7.58 115

(d, J = 7.6 Hz, 2H), 7.41 (d, J = 8.0 Hz, 1H), 7.19 (d, J = 7.6


RS

C A

dva

nce

s A

ccep

ted

Man

usc

rip

t

Dow

nloa

ded

on 2

8 Se

ptem

ber

2012

Publ

ishe

d on

27

Sept

embe

r 20

12 o

n ht

tp://

pubs

.rsc

.org

| do

i:10.

1039

/C2R

A22

302C

View Online



Hz, 2H), 6.88-6.83 (m, 4H), 6.62 (d, J = 7.6 Hz, 2H), 5.4 (s,

2H); 13C NMR (DMSO-d6, 100 MHz): δ 158.5, 156.3, 153.3,

142.4, 135.5, 130.3 (2C), 127.2 (2C), 126.8, 121.8 (2C), 121.6

(2C), 120.5, 118.5, 115.4, 115.3, 110.7, 46.8; IR (KBr): 3253,

2803, 1611, 1515, 1443, 1266, 1244, 1170, 839 cm-1; HRMS 5

(ESI): calcd for C20H17N2O2 (M+H)+ 317.1290, found

317.1288; MS (ESI): m/z ([M+H]+): 317.2

4-(1-(3,4-Dihydroxybenzyl)-1H-benzo[d]imidazol-2-

yl)benzene-1,2-diol (4b) 10

Off white solid, mp 236-238 °C; 1H NMR (DMSO-d6, 400

MHz): δ 9.46 (bs, 1H), 9.28 (bs, 1H), 8.90-8.83 (m, 2H), 7.67

(d, J = 8.0 Hz, 1H), 7.35 (d, J = 8.0 Hz, 1H), 7.21-7.17 (m,

3H), 6.98 (d, J = 7.6 Hz, 1H), 6.82 (d, J = 7.6 Hz, 1H), 6.63

(d, J = 8.0 Hz, 1H), 6.39-6.31 (m, 2H), 5.36 (s, 2H); 13C NMR 15

(DMSO-d6, 100 MHz): δ 153.6, 147.1, 145.4, 145.3, 144.5,

142.6, 135.8, 127.7, 122.0, 121.8, 121.0, 120.3, 118.7, 117.1,

116.6, 115.7, 115.5, 113.4, 110.9, 47.1; IR (KBr): 3378, 1605,

1483, 1453, 1282, 1248, 1125, 759 cm-1; HRMS (ESI): calcd

for C20H17N2O4 (M+H)+ 349.1188, found 349.1176; MS 20

(ESI): m/z ([M+H]+): 349.2

1-(4-(Tert-butyl)benzyl)-2-(4-(tert-butyl)phenyl)-5-methyl-

1H-benzo[d]imidazole (4c)

White solid; mp 231-233 °C; 1H NMR (DMSO-d6, 400 MHz): 25

δ 7.66 (d, J = 8.0 Hz 2H), 7.59 (d, J = 8.0 Hz, 1H), 7.53 (d, J

= 7.6 Hz, 1H), 7.32 (d, J = 8.0 Hz, 2H), 7.22 (s, 1H), 7.06 (d,

J = 8.0 Hz, 2H), 6.92 (d, J = 8.0 Hz, 2H), 5.52 (s, 2H), 2.38

(s, 3H), 1.31 (s, 9H), 1.21 (s, 9H); 13C NMR (DMSO-d6, 100

MHz): δ 152.9, 150.5, 141.3, 136.4, 133.5, 132.7, 128.9 (2C), 30

127.2, 125.9 (2C), 125.6 (2C), 124.1 (2C), 119.3 (2C), 110.3

(2C), 48.0, 34.8, 34.5, 31.3 (3C), 31.2 (3C), 21.8; IR (KBr):

3673, 2962, 1462, 1332, 1268, 992, 843, 809 cm-1; HRMS

(ESI): calcd for C29H35N2 (M+H)+ 411.2800, found 411.2798;

MS (ESI): m/z ([M+H]+): 411.4 35

1-(4-(Tert-butyl)benzyl)-2-(4-(tert-butyl)phenyl)-4,5-

dichloro-1H-benzo[d]imidazole (4d)

White solid; mp 231-233 °C; 1H NMR (DMSO-d6, 400 MHz):

δ 7.82 (d, J = 8.0 Hz 1H), 7.70 (d, J = 8.0 Hz, 2H), 7.57-7.52 40

(m, 3H), 7.32 (d, J = 8.0 Hz, 2H), 6.90 (d, J = 7.6 Hz, 2H),

5.60 (s, 2H), 1.35 (s, 9H), 1.22 (s, 9H); 13C NMR (CDCl3, 100

MHz): δ 155.7, 152.9, 150.2, 142.0, 135.8, 132.6, 128.4 (2C),

126.0, 125.3 (2C), 125.3 (3C), 125.2 (3C), 119.9, 111.9, 47.4,

33.9 (2C), 30.8 (3C), 30.7 (3C); IR (KBr): 3433, 3059, 2963, 45

1609, 1460, 1445, 1304, 1118, 838 cm-1; HRMS (ESI): calcd

for C28H31N2Cl2 (M+H)+ 465.1864, found 465.1857; MS

(ESI): m/z ([M+H]+): 465.3

2-(Pyridin-4-yl)-1-(pyridin-4-ylmethyl)-1H-50

benzo[d]imidazole (4e)


MHz) δ 8.48 (d, J = 8.0 Hz, 2H), 8.35 (d, J = 8.0 Hz, 2H),

7.48 (d, J = 8.0 Hz, 2H), 7.16 (d, J = 8.0 Hz, 2H), 6.53-6.42

(m, 3H), 6.18 (d, J = 8.0 Hz, 1H), 5.82 (s, 2H); 13C NMR 55

(DMSO-d6, 100 MHz) δ 150.5, 150.1, 150.0, 149.8, 149.5,

145.7, 142.5, 137.1, 136.1, 123.7, 123.0, 122.9, 122.6, 122.5,

121.1, 119.8, 111.1, 46.6; IR (KBr): 3415, 3036, 1603, 1414,

827, 749 cm-1; HRMS (ESI): calcd for C18H15N4 (M+H)+

287.1297, found 287.1294; MS (ESI): m/z ([M+H]+): 287.2 60

1-((1H-Indol-2-yl)methyl)-2-(1H-indol-2-yl)-1H-

benzo[d]imidazole (4f)


MHz): δ 11.7 (bs, 1H), 11.0 (bs, 1H), 8.31 (d, J = 8.0 Hz, 65

1H), 7.88 (s, 1H), 7.68 (d, J = 8.0 Hz, 1H), 7.57 (d, J = 7.6

Hz, 1H), 7.49 (d, J = 8.0 Hz, 1H), 7.32 (d, J = 8.0 Hz, 1H),

7.25-7.16 (m, 5H), 7.04 (t, J = 7.6 Hz, 2H), 6.85 (t, J = 7.6

Hz, 1H), 5.83 (s, 2H); 13C NMR (DMSO-d6, 100 MHz): δ

149.5, 142.8, 136.3, 136.0, 135.4, 126.5, 126.4, 125.5, 123.5, 70

122.3, 121.5, 121.3 (2C), 121.2, 120.2, 118.8, 118.1 (2C),

111.8, 111.7, 110.5, 110.2, 104.8, 40.7; IR (KBr): 3418, 3047,

1617, 1569, 1452, 1391, 1242, 1013, 937, 746 cm-1; HRMS

(ESI): calcd for C24H19N4 (M+H)+ 363.1610, found 363.1604;

MS (ESI): m/z ([M+H]+): 363.2 75

Acknowledgments

The author (TBK) thanks Dr V. Dahanukar for his

encouragement. The authors thank the analytical group of 80

DRL for spectral data.

Notes and references

1. (a) B. M. Trost, Science 1991, 254, 1471. (b) R. A. Sheldon,

CHEMTECH 1994, 38. (c) R. A. Sheldon, Pure Appl. Chem.

2000, 72, 1233. (d) Trost, B. M. Acc. Chem. Res. 2002, 35, 85

695. (e) D. B. G. Williams and M. C. Lawton, Green Chem.

2008, 10, 914.

2. F. Kallashi, D. Kim, J. Kowalchick, Y. J. Park, J. A. Hunt, A.

Ali, C. J. Smith, M. L. Hammond, J. V. Pivnichny, X. Tong, S.

S. Xu, M. S. Anderson, Y. Chen, S. S. Eveland, Q. Guo, S. A. 90

Hyland, D. P. Milot, A. M. Cumiskey, M. Latham, L. B.

Peterson, R. Rosa, C. P. Sparrow, S. D. Wright and P. J.

Sinclair, Bioorg. Med. Chem. Lett. 2011, 21, 558.

3. (a) M. R. Grimmett. in Comprehensive Heterocyclic

Chemistry (Eds: A. R. Katritzky, C. W. Rees), Pergamon 95

Press, New York 1984, vol. 5, p. 457; (b) J. B. Wright, Chem.

Rev. 1951, 48, 397; (c) R. W. Middleton and D. G. Wibberley,

J. Heterocycl. Chem. 1980, 17, 1757; (d) T. Hisano, M.

Ichikawa, K. Tsumoto and M. Tasaki, Chem. Pharm. Bull.

1982, 30, 2996; (e) J. D. Geratz, F. M. Stevens, K. L. 100

Polakoski and R. F. Parrish, Arch. Biochem. Biophys. 1979,

197, 551.

4. (a) P. N. Preston, in Chemistry of Heterocyclic Compounds,

Vol. 40, ed. A. Weissberger and E. C. Taylor, John Wiley and

Sons, 1981; (b) D. W. Hein, R. J. Alheim and J. J. Leavitt, J. 105

Am. Chem. Soc., 1957, 79, 427 (c) Y. -C. Chi, C.-M. Sun,

Synlett, 2000, 591; (d) W. Huang and R. M. Scarborough,

Tetrahedron Lett. 1999, 40, 2665; (e) L. M. Dudd, E.

Venardou, E. Garcia-Verdugo, P. Licence, A. J. Blake, C.

Wilson and M. Poliakoff, Green Chem. 2003, 5, 187. 110

5. (a) A. Czarny, W. D. Wilson and D. W. Boykin, J. Heterocycl.

Chem. 1996, 33, 1393; (b) R. R. Tidwell, J. D. Geratz, O.

Dann, G. Volz, D. Zeh and H. Loewe, J. Med. Chem. 1978,

21, 613; (c) T. A. Fairley, R. R. Tidwell, I. Donkor, N. A.

Naiman, K. A. Ohemeng,; R. J. Lombardy, J. A. Bentley and 115

M. Cory, J. Med. Chem. 1993, 36, 1746; (d) P. N. Preston, in

Chemistry of Heterocyclic Compounds, vol. 40,

Benzimidazoles and Congeneric Tricyclic Compounds (Eds:

A. Weissberger, E. C. Taylor), Wiley, New York, 1981, part 1,

p. 6. (e) Grimmett M. R. in Comprehensive Heterocyclic 120

Chemistry, vol. 5, Imidazoles and their Benzo Derivatives

(Eds: A. R. Katritzky, C. W. Rees), Pergamon Press, Oxford,


RS

C A

dva

nce

s A

ccep

ted

Man

usc

rip

t

Dow

nloa

ded

on 2

8 Se

ptem

ber

2012

Publ

ishe

d on

27

Sept

embe

r 20

12 o

n ht

tp://

pubs

.rsc

.org

| do

i:10.

1039

/C2R

A22

302C

View Online



1984, p. 457; (f) Y. Wang, K. Sarris, D. R. Sauer and S. W.

Djuric, Tetrahedron Lett. 2006, 47, 4823; (g) T. Benincori, F.

Sannicolo, J. Heterocycl. Chem. 1998, 25, 1029; (h) K.

Bourgrin, A. Loupy and M. Soufiaoui, Tetrahedron 1998, 54,

8055; (i) G. V. Reddy, V. V. V. N. S. Ramarao, B. Narsaiah 5

and P. S. Rao, Synth. Commun. 2002, 32, 2467; ( j) A. Ben-

Alloum, S. Bakkas and M. Soufiaoui, Tetrahedron Lett. 1998,

39, 4481; (k) K. Niknam and A. Fatehi-Raviz, J. Iran. Chem.

Soc. 2007, 4, 438.

6. (a) J. G. Smith and I. Ho, Tetrahedron Lett. 1971, 12, 3541; 10

(b) K. Nagata, T. Itoh, H. Ishikawa and A. Ohsawa,

Heterocycles, 2003, 61, 93; (c) T. Itoh, K. Nagata, H. Ishikawa

and A. Ohsawa, Heterocycles 2004, 63, 2769; (d) S. Perumal,

S. Mariappan and S. Selvaraj, Arkivoc, 2004, 8, 46; (e) M.

Chakrabarty, S. Karmakar, A. Mukherji, S. Arima and Y. 15

Harigaya, Heterocycles, 2006, 68, 967; (f) P. Sun and Z. Hu, J.

Heterocycl. Chem., 2006, 43, 773; (g) P. Salehi, M. Dabiri, M.

A. Zolfigol, S. Otokesh and M. Baghbanzadeh, Tetrahedron

Lett. 2006, 47, 2557; (h) R. Varala, A. Nasreen, R. Enugala

and S. R. Adapa, Tetrahedron Lett., 2007, 48, 69; (i) B. H. 20

Kim, R. Han, J. S. Kim, Y. M. Jun, W. Baik and B. M. Lee,

Heterocycles, 2004, 63, 41.

7. (a) A. Ben Alloum, K. Bougrin and M. Soufiaoui,

Tetrahedron Lett. 2003, 44, 5935; (b) P. Gogoi and D.

Konwar, Tetrahedron Lett. 2006, 47, 79; (c) T. Itoh, K. 25

Nagata, H. Ishikawa and A. Ohsawa, Heterocycles 2004, 62,

197; (d) R. Trivedi, S. K. De and R. A. Gibbs, J. Mol. Catal.

A: Chem. 2006, 245, 8.

8. (a) A. Couture and P. Grandclaudon, Heterocycles 1984, 22,

1383; (b) R. H. Tale, Org. Lett. 2002, 4, 1641; (c) D. Alagille, 30

R. M. Baldwin and G. D. Tamagnan, Tetrahedron Lett. 2005,

46, 1349; (d) T. Itoh and T. Mase, Org. Lett. 2007, 9, 3687.

9. (a) C. W. Phoon, P. Y . Ng, A. E. Ting, S. L. Yeo and M. M.

Sim, Bioorg. Med. Chem. Lett. 2001, 11, 1647; (b) E.

Kashiyama, I. Hutchinson, M. S. Chua, S. F. Stinson, L. R. 35

Phillips, G. Kaur, E. A. Sausville, T. D. Bradshaw, A. D.

Westwell and M. F. G. Stevens, J. Med. Chem. 1999, 42,

4172; (b) D. E. Boger, J. Org. Chem. 1978, 43, 2296 .

10. Ben-Alloum, S. Bakkas and M. Soufiaoui, Tetrahedron Lett.

1997, 38, 6395. 40

11. (a) A. Correa, O. G. Mancheno and C. Bolm, Chem. Soc. Rev.

2008, 37, 1108; (b) B. D. Sherry and A. Furstner, Acc. Chem.

Res. 2008, 41, 1500; (c) C. Bolm, J. Legros, J. Le Paih and L.

Zani, Chem. Rev. 2004, 104, 6217; (d) A. Furstner and R.

Martin, Chem. Lett. 2005, 34, 624; (e) D. D. Diaz, P. O. 45

Miranda, J. I. Padron and V. S. Martın, Curr. Org. Chem.

2006, 10, 457.

12. (a) B. P. Bandgar and V. T. Kamble, Green Chem. 2001, 3,

265; (b) T. Hatakeyama and M. Nakamura, J. Am. Chem. Soc.

2007, 32, 9844; (c) V. T. Kamble, B. P. Bandgar, Satish B. G. 50

Suryawanshi and S. N. Bavikar, Aust. J. Chem. 2006, 59, 837;

(d) R. Surasani, D. Kalita, A. V. D. Rao, K. Yarbagi and K. B.

Chandrasekhar, J. Fluorine Chem, 2012, 135, 91; (e) B. P.

Bandgar,; V. T. Kamble and A. Kulkarni, Aust. J.

Chem. 2005, 58, 607; (f) X.-L. Fang, R. -Y. Tang, X. -G. 55

Zhang and J. –H. Li, Synthesis 2011, 1099.

13. J.-P. Wan, S.-F. Gan, J.-M. Wu and Y. Pan, Green. Chem.

2009, 11, 1633.

14. Y. Kim, M. R. Kumar, N. Park, Y. Heo and S. Lee, J. Org.

Chem. 2011, 76, 9577. 60

15. M. Shen and T. G. Driver, Org. Lett. 2008, 10, 3367.

16. R. M. Acheson and M. S. Verlander, J. Chem. Soc., Perkin

Trans. 1, 1973, 2348.

17. M. D. Bhor and B. M. Bhanage, Synth. Commun., 2010, 40,

1743. 65

18. J. C. Lewis, A, M. Berman, R. G. Bergman and J. A. Eliman,

J. Am. Chem. Soc. 2008, 130, 2493.

19. D. Yang, H. Fu, L. Hu, Y. Jiang and Y. Zhao J. Org. Chem.,

2008, 73, 7841.

20. S. Rostamizadeh, A. M. Amani, R. Aryan, H. R. Ghaieni and 70

L. Norouzi, Monatsh Chem. 2009, 140, 547.

21. L. S. Tan, R. Kannan, J. C. Spain and L. J. Nadeau, U. S.

Patent No US7495106 B1, 2009.

22. K. Xie, Z. Yang, X. Zhou, X. Li, S. Wang, Z. Tan, X. An, C.-

C. Cuo, Org. Lett. 2010, 12, 1564 75

23. Y. Cheng, J. Yang, Y. Qu, and P. Li, Org. Lett., 2012, 14, 98.

24. J. N. Moorthy and, I. Neogi, Tetrahedron Lett. 2011, 52, 3868.

25. M. Rekha, A. Hamza, B. R. Venugopal and N. Nagaraju, Chin.

J. Catal., 2012, 33, 439.

26. L. D. Luca and A. Porcheddu, Eur. J. Org. Chem. 2011, 29, 80

5791.


RS

C A

dva

nce

s A

ccep

ted

Man

usc

rip

t

Dow

nloa

ded

on 2

8 Se

ptem

ber

2012

Publ

ishe

d on

27

Sept

embe

r 20

12 o

n ht

tp://

pubs

.rsc

.org

| do

i:10.

1039

/C2R

A22

302C

View Online


Graphical Abstract

H2O

NH2

XH

R2OHC

X

NR2

(X = NH, S)

FeF3

Open to air

N

NR2

R2

R

R1

R

R1

R2OHC (X = NH)2

R

R1

We describe first FeF3 mediated green synthesis of 2-substituted 1,3-benzazoles and 1,2-

disubstituted benzimidazoles in water under open air.


RS

C A

dva

nce

s A

ccep

ted

Man

usc

rip

t

Dow

nloa

ded

on 2

8 Se

ptem

ber

2012

Publ

ishe

d on

27

Sept

embe

r 20

12 o

n ht

tp://

pubs

.rsc

.org

| do

i:10.

1039

/C2R

A22

302C

View Online


Documents

Catalysis by FeF3 in water: a green synthesis of 2-substituted 1,3-benzazoles and 1,2-disubstituted benzimidazoles