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Synthesis of benzoxazoles and benzothiazoles

5.1 Introduction:

Benzoxazoles and benzothiazoles belong to an important class of molecules and are

common heterocyclic scaffolds in biologically active and pharmaceutically significant

compounds. Benzoxazoles are found in a variety of natural products1-2

and are important

scaffolds in drug discovery.3-5

Appropriately substituted benzoxazole derivatives have found

diverse therapeutic activities including antibiotic,6

antimicrobial,7–10

antiviral,11

topoisomerase I

and II inhibitory,12

and antitumor activities.13

anticancer agent14-15

NSC-693638, L-697,661,

antiviral,16

and antibacterials17

UK-1, AJI9561. Recent studies showed substituted 2-

benzylbenzoxazoles have antibacterial, antifungal,18

antimicrobial19-21

and anti-measles virus

activities22

(Figure 1).

N

O

O O

R1

ON

FOHN

O NH

Cl

Cl

NHO

Me

Et

N

O

X

R N

O N

NH

Cl

Cl

Me

N

R1=Me; UK-1; R1=H; AJI9561 L-697,661

2-Benzylbenzoxazoles NSC 693638

Figure 1. Some biologically active benzoxazoles

The small and simple benzothiazole nucleus is present in compounds involved in research

aimed at evaluating new products that possess interesting biological activities like- antitumour,23-

26antimicrobial,

27-29antitubercular,

30antimalarial,

31anticonvulsant,

32,33anthelmintic,

34analgesic

and anti-inflammatory activity,35,36

The benzothiazole ring is present in various marine or

terrestrial natural compounds, which have useful biological activities. Heterocycles containing

the thiazole moiety are present in many natural products such as bleomycin, epothilone A,

lyngbyabellin A & dolastatin 10.37

Benzothiazole is a privileged bicyclic ring system. Due to

their important pharmaceutical utilities, the synthesis of these compounds is of considerable


interests. Riluzole is a drug containing benzothiazole derivative used to treat amyotrophic lateral

sclerosis. It delays the onset of ventilator-dependence or tracheostomy in selected patients and

may increase survival by approximately 3–5 months. Benzothiazoles and benzoxazoles are a

class of heterocycles that possess diverse array of biological properties (Figure 2).38-44

N

S

F

F

FNH

O OCH2COOH

FN

SS

O

O

NH2

O

N

S

O

NH

O

NH

NH2

NH NH

N

SNH2

N

SNH2

O

F

F

F

Figure 2. Some biologically active benzothiazoles

5.1.1 Review of literature:

A vast number of methods reported in the literatures for the synthesis of benzoxazoles and

benzothiazoles due to their potent biological and material properties. This section summarized

some of the important synthesis of benzoxazoles and benzothiazoles and their methods.

Speier approach (1987)45

Speier G. reported 2-substituted benzoxazoles in good yields by oxidation of N-alkylidene-2

hydroxyanilines in presence of copper(I) chloride in pyridine as a catalyst.

N

OH

Ph1/2[CuClpy(OMe)l2

-MeOH; -CuClpy

N

O

Ph

1 2

Scheme 1. Synthesis of 2-substituted benzooxazole


Poissonnet approach (1997)46

Poissonnet G. reported various substituted 1,2-benzoxazoles with good yields from

salicylaldoximes and orthohydroxyphenyketoximes via intramolecular Mitsunohu reaction.

R2

R3

R4

OH

NOH

R1

DEAD/PPh 3

THFO

N

R1

R2

R3

R4

3 4

Scheme 2. Synthesis of 1,2-benzoxazoles via intramolecular Mitsunohu reaction

Varma approach (1997)47

Varma et al reported 2-arylbenzoxazoles via the oxidative intramolecular cyclization of phenolic

Schiff’s bases, using iodobenzene diacetate (IBD) as an oxidant in acetonitrile or methanol at

room temperature.

R2

OH

N

R1

CH3CN

AcOH

R2

O

N

R1

5 6

Scheme 3. Synthesis of 2-arylbenzoxazoles via the oxidative intramolecular cyclization of phenolic Schiff’s bases

Ying-Hung approach (1998)48

Ying-Hung et al synthesized 2-arylbenzothiazoles and 2-arylbenzoxazoles in good yields from

trihalomethyl aromatics with o-aminothiophenol and o-aminophenol in polyphosphoric acid

(PPA).

CX3 +NH2

HZ

X = Cl, F Z = S, O

PPA

Z

N

+ HCl

7 8 9

Scheme 4. Synthesis of 2-arylbenzothiazoles and 2-arylbenzoxazoles


Loupy approach (1999)49

Loupy et al performed Beckmann rearrangements of benzaldehyde and 2-hydroxyacetophenone

oxime for the synthesis of benzoxazole in the presence of anhydrous zinc chloride and under

solvent free condition.

N

OH

OH

CH3

N

O

CH3

10 11

ZnCl2

microwave

Scheme 5. Synthesis of 2-arylbenzoxazoles

Saitz approach (2001)50

Saitz et al described a rapid method for the synthesis of four different heterocyclic systems of

fused aryl oxazoles in reasonable yields.

O

N

O

Ar KOH, MeOH

O

NAr

12 13

Scheme 6. Synthesis of benzoxazoles

Chang approach (2002)51

Chang et al reported the condensation arylaldehydes with 2-aminophenols and subsequent DDQ-

promoted oxidative cyclization reactions for the synthesis of 2-arylbenzoxazoles.

OH

NH2

R

ArCHO

MeOH, 450C

OH

N Ph

RDDQ

CH2Cl2

O

N

PhR

O

NH

PhR

14 15 16 17

Scheme 7. DDQ-promoted synthesis of 2-arylbenzoxazoles

Pottorf approach (2002)52

Pottorf et al reported two efficient methods for the solution-phase synthesis of benzoxazoles.

Readily available reagents are used along with the short reaction time, no additives, and simple


work-up and isolation of the product make the current approach a feasible and attractive protocol

for generation of benzoxazole.

OH

NH2

R +

O

Cl base

O

NH

Ph

Ph

O

O

R Lewis AcidO

N

PhRa)

OH

NH2

R +

O

Cl

OMe

OMe

OMemicrowave

O

N

OMe

OMe

OMe

R

18 19 20 21

22 23 24

b)

Scheme 8. (a) Conventional synthesis of benzoxazoles through diacylated intermediate.(b) Microwave-assisted

synthesis of benzoxazoles in a one-pot acylation/cyclization step.

Matsushita approach (2004)53

Matsushita et al reported the preparation of an array of benzothiazoles from polymer-bound

esters. Polymerbound esters were treated with 2-aminothiophenols or 1,2-phenylenediamines in

the presence of a Lewis acid to afforded the corresponding benzothiazole or benzimidazole

cleavage products.

O

N

R1

R2

O

O +SH

NH2

AlMe3

SH

NH

O

O

NR

2

R1

S

N O

N R2

R1

25 26 27 28

Scheme 9. Synthesis of benzothiazole cleavage product

Nadaf approach (2004)54

Nadaf et al reported Room temperature ionic liquid promoted regioselective synthesis of 2-aryl

benzoxazoles and benzthiazoles under ambient conditions. 1-butylimidazolium tetraflouroborate

([Hbim]BF4) and 1,3-di-n-butylimidazolium tetrafluoroborate ([bbim]BF4) used as reaction

media and promoters.


XH

NH2

R

+Cl

O

R’

R’’

IL/280C X

N

R

R’

R’’

X = O, S

29 30 31

Wang approach (2006)55

Wang et al reported a simple and efficient one step synthesis of benzoxazoles from carboxylic

acids. The use of commercially available PS-PPh3 resin combined with microwave heating

delivered a variety of benzoxazoles and benzimidazoles in high yields and purities.

R1

OH

O

+OH

NH2R2

CH3CN, MW

N

O

R1

R2

32 33 34

Scheme 11. Synthesis of benzoxazoles from carboxylic acids and 1,2-aminophenol with PS-PPh3/CCl3CN

Moghaddam approach (2006)56

Moghaddam et al reported rapid and efficient condensation reactions of 2-aminothiophenol and

2-aminophenol with various aldehydes to afford the corresponding 2-substituted benzothiazole

and benzoxazole derivatives in good to excellent yields. The reaction was carried out using I2 in

solvent-free condition.

XH

NH2

+R H

O I2 N

X

R

X = O, S R = Aryl

35 36 37

Scheme 12. Iodine catalyzed synthesis of benzothiazole and benzoxazole derivatives

Spatz approach (2007)57

Spatz et al reported diversity oriented two-step synthesis procedure for the preparation of highly

substituted benzoxazoles and benzothiazoles.

Scheme 10. Ionic liquid promoted synthesis of benzoxazoles and benzthiazoles


NH2 R1

+R

2R

3

O

R4

Z

O

+ +

CN

X

R5

U -4CRNH

R2

R3

N

R1

R4

O

Z XR

5

38 39 40 41 42

NH

R2

R3

N

R1

R4

O

Z XR

5

42

N

R2

R3

N

R1

R4

O

Z

R5

43

CS2CO3

DME

Mohammadpoor-Baltork approach (2007)58

Mohammadpoor-Baltork et al reported a new and efficient method for the preparation of

benzoxazoles and benzothiazoles from reactions of orthoesters with o-substituted

aminoaromatics and 2-amino-3-hydroxypyridine in the presence of catalytic amounts of the

moisture stable, inexpensive ZrOCl2·8H2O under solvent-free conditions

NH2

OH

+ CH3C(OCH2CH3)3

ZrOCl2.8H2O

r.t.

N

X

CH3 + 3 CH3CH2OH

44 45 46 47

Scheme 14. ZrOCl2·8H2O catalyzed synthesis of benzoxazoles and benzothiazoles

Kaul approach (2007)59

Kaul et al reported one-pot synthesis of benzoxazoles in excellent yield by condensation of

carboxylic acids with 2-amino-phenol in presence of N,N-Dimethylchlorosulfitemethaniminium

chloride (SOCl2-DMF) as an efficient reagent.

RCOOH +

NH2

OH

Me2N=CH-O-SOCl2

O

N

R

48 49 50

Scheme 15. SOCl2-DMF catalyzed one pot synthesis of benzoxazoles

Scheme 13. Combinatorial synthesis of benzoxazoles and benzothiazoles via U-4CR

and copper-catalyzed cross-coupling strategy


Radi approach (2008)60

Radi et al reported a one-pot, two-step microwave-assisted synthesis of highly functionalized

benzoxazoles using solid-supported reagents (SSRs).

N

N

MeS

O

O

R1

NH2

OH

R2

R3

+O

NR

1

R2

R3

51 52 53

Scheme 16. SSRs catalyzed synthesis of benzoxazoles

Costa approach (2008)61

Costa et al synthesized a series of new benzoxazolylalanine derivatives bearing (oligo)thiophene

units at the side chain.

NH2

OH

CO2MeBOC-NH

+S

OHC

R

n

ethanol

reflux

N

OH

CO2Me

BOC-NH

S

R

n N

O

CO2Me

BOC-NH

S

R

nLTA

DMSO

54 55 56 57

Scheme 17. Synthesis of fully protected (oligo)thienylbenzoxazolyl-alanine derivatives

Shoar approach (2009)62

Shoar et al reported efficient and rapid synthesis of benzoxazoles catalyzed by MCM-41, a

Green and Reusable Catalyst.

OH

NH2X

+MCM-41 N

OX

R

58 59 60

O

Cl

R

Solvent free

Scheme 18. The condensation reaction of 2-aminophenols with benzoyl chlorides using MCM-41 as catalyst


Blacker approach (2009)63

Blacker et al reported oxidative conversion of amines into benzoxazoles using hydrogen transfer

catalysis. The optimal system utilises 1 mol % of the Shvo catalyst, with

dimethoxybenzoquinone as the hydrogen-accepting terminal oxidant.

R1

NH2 +

OH

NH2

R2

R3

1% {[(ç5-Ph4C4CO)]2H}Ru2(CO)4(ì-H)},

N

O

R1

R2

R3

61 62 63

Scheme 19. Oxidative approaches to benzoxzoles by hydrogen transfer catalysis

Chen approach (2009)64

Chen et al reported an efficient method for the synthesis of 2-(2’-hydroxyphenyl)benzoxazole by

using palladium-mediated oxidative cyclization.

N

OH

OH

R2R

1

Pd (II)

N

O

OH

R2

R1

64 65

Scheme 20. Pd(II)-catalyzed synthesis of 2-(2’-hydroxyphenyl)benzoxazole

Patil approach (2010)65

Patil et al reported synthesis of 2-Substituted benzoxazole and benzothiazole from condensation

of aldehyde and 2-aminophenol or 2-aminothiophenol via a one-pot process using diethyl bromo

phoshonate and tert-butyl hypochlorite.

XH

NH2

+ RCHOA or B

Acetonitrile

N

X

R

66 67 68

X = S, O

A = diethyl bromophosphonate

B = tert-butyl hypochlorite

Scheme 21. Synthesis of benzoxazole and benzothiazole


Srivani approach (2010)66

Srivani et al reported an efficient method for the preparation of benzoxazoles by reacting

aminophenols with orthoesters in the presence of silica-supported tin exchanged silicotungstic

acid catalyst under mild conditions with high yield.

OH

NH2

+ CHOEt3catalyst

CH3CN

N

O

69 70 71

Scheme 22. Silica-supported synthesis of benzoxazoles

Tao approach (2010)67

Tao et al performed direct coupling of 1,1-dibromoethenes with 2-aminophenols to form the

corresponding benzoxazoles under mildly basic reaction conditions.

Br

Br

MeO2C

+NH2

OH

DABCO/NMP

N

O

CO2Me72 73 74

Scheme 23. The new route for the preparation of benzoxazoles

Reyes approach (2011)68

Reyes et al synthesized 2-phenylbenzoxazoles in moderate to good yields by reaction of the

substituted o-aminophenols with benzaldehydes in the presence of one equivalent of potassium

cyanide as an equimolecular catalyst in N,N-dimethylformamide at room temperature.

OH

NH2

+

O

H 1 eq. KCN

DMF

N

O

75 76 77

Scheme 24. One pot protocol for the preparation of 2-phenylbenzoxazoles


Chen approach (2011)69

Chen et al reported a simple protocol for the preparation of 2-arylbenzoxazoles, based on the

oxidation of phenolic Schiff bases with o-iodoxybenzoic acid (IBX).

OH

NH2

+

CHO

R

EtOAc, MS

OH

N

R

IBX, MS

O

N

78 79 80 81

Scheme 24. Synthesis of 2-arylbenzoxazoles by IBX oxidation

Riadi approach (2011)70

Riadi et al reported a library of benzoxazoles and benzothiazoles by condensation of o-

aminophenol, and o-aminothiophenol respectively with aromatic aldehydes in the presence of

catalytic amounts of Animal Bone Meal (ABM) and Lewis acids doped ABMs.

XH

NH2

+

CHO

R

ABMs Catalyst

X

N

RToluene

X = O, S X = O, S

82 83 84

Scheme 25. Synthesis of benzoxazoles and benzothiazoles catalyzed by ABM

López-Ruiz approach (2011)71

López-Ruiz et al reported a novel, one-pot, phenylboronic acid catalyzed, cyanide promoted

synthesis of 2-(2-hydroxyphenyl) benzoxazoles from salicylaldehydes and o-aminophenols.

O

H

OHR1

+NH2

OH

PhB(OH)2

KCN O

N

OHR2 R

1

R2

85 86 87

Scheme 26. Synthesis of various substituted 2-phenylbenzoxazoles


Madhusudana Reddy approach (2011)72

Madhusudana Reddy et al reported Zn(OAc)2 _2H2O efficiently catalyzed the condensation

reaction between 2-aminophenol and various araldehydes to afford the 2-substituted

benzoxazoles in good to excellent yields.

O

H

R

NH2

OH

+Zn(OAc)2.2H2O

O

N

R

88 89 90

Scheme 27. Zinc acetate–catalyzed synthesis of benzoxazoles

Bachhav approach (2011)73

Bachhav et al reported a straightforward, efficient and more sustainable catalyst-free method for

the synthesis of benzoxazole ring system in glycerol as green solvent.

NH2

OH

+

CHO

Glycerol H2O

O

N

91 92 93

Scheme 28. Preparation of 2-arylbenzoxazole

Wen approach (2011)74

Wen et al reported an efficient method for quick preparation of benzothiazoles and benzoxazoles,

through T3P-mediated microwave reactions of o-aminobenzenethiol and o-aminophenol with

diverse carboxylic acids.

NH2

X

+OH R

OT3P (in AcOEt)

DIPEAX

N

R

94 95 96X = S, O X = S, O

Scheme 29. T3P-mediated synthesis of benzothiazoles and benzoxazoles


5.1.2 Present work:

5.1.2.1 Objective

The benzoxazole and benzothiazole skeletons may be found in numerous pharmaceutical

agents with a diverse spectrum of biological properties. Although a wide range of methods are

available for synthesizing benzoxazoles75-79

and benzothiazoles,80-84

a real need exists for new

and simple procedures that support many kinds of structural diversity and various substitution

patterns in the target library.

The most commonly used synthetic method to access benzoxazole and benzothiazole

consists in the condensation of either o-aminobenzenethiol or o-aminophenol with substituted

aldehydes,85

nitriles,86

acyl chlorides,87

or carboxylic acids.88-90

These methods often require long

reaction times and strong conditions. A recent example describes the synthesis of benzoxazoles

and benzothiazoles from alcohol.91

However, some of these methods suffer from one or more of the following drawbacks

such as strong acidic conditions, long reaction times, low yields of the products, tedious workup,

need for excess amounts of reagent and the use of toxic reagents, catalysts or solvents. Therefore,

there is a strong demand for a highly efficient and environmentally benign method for the

synthesis of these heterocycles. Thus, an efficient and convenient chemical process or method

for the synthesis of biologically active compounds from the simple reagent is always challenging

task for chemists working in the field of organic synthesis. Thus, in this chapter, firstly we report

a synthetic method for the synthesis of benzoxazoles and benzothiazoles by using potassium

ferrocyanide as a catalyst, under water media. Secondly we report two synthetic methods for the

synthesis of benzoxazoles and benzothiazoles by using potassium ferrocyanide as a catalyst.

In recent years, potassium ferro-cyanide has gained special attention as a catalyst in

organic synthesis like synthesis of anti-Alzheimer drug(-) Galanthamine92

due to its high

stability, oxidizing power selectivity and a nontoxic by product Fe(III).It promoted oxidative

cyclization of 5-S Cysteinyldopa93

. X. Z. Yu et al studied the liberation of cyanide into the

environment which has terristerial importance for ecosystem94

. M. A. Gaffar et al studied the

kinetic of the potassium ferro cyanide95

because of many advantages such as excellent solubility

in water, uncomplicated handling, inexpensiveness, eco-friendly nature, readily available and

high reactivity.


5.1.3 Result and Discussion

5.1.3.1 K4[Fe(CN6)] catalyzed synthesis of benzoxazoles in water media

Firstly, we report the synthesis of 2-substituted-benzoxazoles by condensation of 2-

aminophenol respectively with various aromatic aldehydes using potassium ferrocyanide as an

efficient catalyst in water media (Scheme 5.1 and Table 1).

NH2

OH

+

CHO

K4[Fe(CN)6]

H2O

N

O R’’R’

97 98 99a-kR’’ R’

Scheme 5.1 K4[Fe(CN6)] catalyzed synthesis of benzoxazoles in water media

At first we focused on the reaction of 2-aminophenol and aromatic aldehydes. In a typical

procedure, 2-aminophenol (1 mmol) with benzaldehyde (1 mmol) in the presence of a catalytic

amount of potassium ferrocyanide (0.5 mmol) in water media afforded the desired 2-phenyl-

benzoxazole in 92% yield (Entry 1, Table 1). The reaction then was applied to a variety of

aromatic aldehydes (Scheme 5.1 and Table 1). Most of these reactions proceeded in relatively

short times and pure products were obtained by recrystallization with methanol.

The generality of this reaction was authenticated by the use of various aromatic

aldehydes containing electron-donating and electron-withdrawing groups and various 1,2-

diamines (Table 2). Aldehydes containing electron withdrawing groups enhanced the rate of

reaction because of increase in the electrophilic character at aldehydic carbon. In case of 2-

aminophenol, 2-amino-4-nitrophenol reacted slowly because of electron withdrawing nature of

nitro group on aromatic ring, which decrease the nucleophilic character of 1,2-diamine. Finally,

our investigations showed that 2-aminophenol reacts smoothly with aromatic aldehydes in the

presence of potassium ferrocyanide as a catalyst in water media.

Table 1: Synthesis of benzoxazoles in water media

Entry Substituted 2-

aminophenol

Aldehydes Product (99a-k) Time

(min)

Yielda

(%)

1

NH2

OH

CHO N

O

99a

13 92


2

NH2

OH

CHO

Br

N

O

Br

99b

12 90

3

NH2

OH

CHO

CH3

N

O

CH3

99c

12 90

4

NH2

OH

CHO

Cl

N

O

Cl

99d

11 88

5 NH2

OH

CHO

Cl N

O

Cl

99e

13 90

6

NH2

OH

CHO

OCH3

N

O

OCH3

99f

14 85

7

NH2

OH

CHO

NO 2

N

O

NO2

99g

10 92

8

NH2

OH

Cl

CHO

OCH 3

OH

N

O

Cl

OH

OCH3

99h

14 82


9

NH2

OH

Cl CHO N

O

Cl

99i15 88

10

NH2

OH

O2N

CHO

CH3

N

O

O2N

CH3

99j

16 90

11

NH2

OH

O2N

CHO

NO 2

N

O

O2N

NO2

99k

15 90

a Isolated yield of the products

5.1.3.2 K4[Fe(CN6)] catalyzed synthesis of benzothiazoles in water media

In continuation of our studies on development of methodology by the condensation of 2-

aminothiophenol and various substituted aldehydes, the behavior of these reactions is similar

to the reactions of 2-aminophenol and aldehydes. The syntheses were carried out simply by

mixing benzothiazoles (1 mmol) with the aldehyde (1 mmol) in the presence of a catalytic

amount (10 mol %) of K4[Fe(CN6)] in water, (Scheme 5.2, Table 2) whereupon the

benothiazoles derivatives were obtained in almost quantitative yield. It is rapid method as

compared to literature reported methods for the synthesis of benzthiazoles. It was ascertained

that a minimum 10 mol % of the catalyst, K4[Fe(CN6)] is required to achieve optimum

conversion. When the amount of catalyst used was less than 10 mol %, yields of

benzthiazoles derivatives were decreased due to incomplete conversion of substrates and any

excess of catalyst beyond this proportion (10 mol %) did not show any further increase in

conversion and yield.


NH2

SH

+

CHO

K4[Fe(CN) 6]

H2O

N

S R’

100 101 102a-jR’

Scheme 5.2 K4[Fe(CN6)] catalyzed synthesis of benzthiazoles in water media

Table 2: Synthesis of benzthiazoles in water media


aminothiaophenol

Aldehydes Product (102a-j) Time

(min)

Yielda

(%)

1

NH2

SH

CHO N

S

102a

12 88

2

NH2

SH

CHO

C H 3

N

S

CH3

102b

13 89

3

NH2

SH

CHO

OCH3

N

S

OCH3

102c

11 86

4

NH2

SH

CHO

O H

N

S

OH

102d

12 84

5

NH2

SH

CHO

Br

N

S

Br

102e

12 92


6

NH2

SH

CHO

Cl

N

S

Cl

102f

13 92

7

NH2

SH

CHO

Cl

N

S

Cl

102g

12 90

8 NH2

SH

CHO

Cl

Cl

N

S

Cl

Cl

102h

14 92

9

NH2

SH

CHO

NO 2

N

S

NO2

102i

10 94

10

NH2

SH

CHO

F

N

S

F

102j

12 89


5.1.3.3 K4[Fe(CN6)] catalyzed synthesis of benzoxazoles and benzothiazole on grinding

In continuation of our work to develop new synthetic methodologies by eliminating water as a

solvent media, we now report an efficient and environmentally benign method for the synthesis

of benzoxazole and benzothiazole in the presence of catalytic amounts of K4[Fe(CN6)] as

catalyst under solventfree conditions.


In order to find optimum reaction conditions, o-aminophenol (103) was treated with

benzaldehyde (104) in the presence of K4[Fe(CN6)] (Scheme 5.3).

NH2

OH

+

CHO

K4[Fe(CN)6]

Grinding

N

O R’’R’

103 104 105a-kR’’ R’

Scheme 5.3 K4[Fe(CN6)] catalyzed synthesis of benzoxazoles on grinding

The optimum molar ratio of o-aminophenol: aldehyde is 1:1 at room temperature under solvent-

free conditions and under these conditions 2-phynylbenzoxazole (105a) was obtained in 94%

yield after 2 min (entry 1, Table 3). To determine the role of K4[Fe(CN6)], the same reaction was

carried out in the absence of catalyst at room temperature, which resulted in 5% of the product,

respectively, after 10 min. These results indicate that K4[Fe(CN6)] exhibits a high catalytic

activity in this transformation.

Table 3: Synthesis of benzoxazoles on grinding


aminophenol

Aldehydes Product (105a-k) Yielda

(%)

1

NH2

OH

CHO N

O

105a

94

2

NH2

OH

CHO

Br

N

O

Br

105b

92

3

NH2

OH

CHO

CH3

N

O

CH3

105c

90


4

NH2

OH

CHO

Cl

N

O

Cl

105d

92

5 NH2

OH

CHO

CF3

F

N

O

CF3

F

105e

93

6

NH2

OH

CHO

OCH3

N

O

OCH3

105f

87

7

NH2

OH

Cl

CHO

NO 2

N

O

NO2

Cl

105g

96

8 NH2

OH

Cl

CHO

CF3

F

N

O

CF3

F

Cl

105h

88

9

NH2

OH

Cl CHO N

O

Cl

105i

90


10

NH2

OH

O2N

CHO

CH3

N

O

O2N

CH3

105j

94

11

NH2

OH

O2N

CHO

NO2

N

O

O2N

NO2

105k

92


Then the generality of the procedure was evaluated by the reactions of various aldehydes with o-

aminophenols. The result demonstrated that the reaction completed within 3 minutes with

excellent yield of the products.

This protocol also extended by the reaction of various aldehydes with o-aminothiphenol (Scheme

5.4)

NH2

SH

+

CHO

K4[Fe(CN)6]

Grinding

N

S R’

106 107 108a-jR’

Scheme 5.4 K4[Fe(CN6)] catalyzed synthesis of benzthiazoles on grinding

2-aminothiophenol (106) was grind with a variety of aldehydes (107) at room

temperature in K4[Fe(CN6)] catalysis under solvent free condition (Table 4). All the reactions

proceed to completion in just 2-3 min. at room temperature without any organic solvent or any

added catalyst. The respective benzthiazoles could be isolated in excellent yields in all the cases

(Table 4).


Table 4: Synthesis of benzthiazoles on grinding


aminothiaophenol

Aldehydes Product (108a-j) Yielda

(%)

1

NH2

SH

CHO N

S

108a

92

2

NH2

SH

CHO

C H 3

N

S

CH3

108b

90

3

NH2

SH

CHO

OCH3

N

S

OCH3

108c

89

4

NH2

SH

CHO

O H

N

S

OH

108d

90

5

NH2

SH

CHO

Br

N

S

Br

108e

92

6

NH2

SH

CHO

Cl

N

S

Cl

108f

94


7

NH2

SH

CHO

Cl

N

S

Cl

108g

91

8 NH2

SH

CHO

CF3

F

N

S

F

CF3

108h

94

9

NH2

SH

CHO

NO 2

N

S

NO2

108i

95

10

NH2

SH

CHO

F

N

S

F

108j

90


The possible mechanism of this reaction is shown in Scheme 6. The K4[Fe(CN)6]

increase the electrophilic character at aldehydic carbon, which will facilitate the nucleophilic

addition of 2-aminothiophenol or 2-aminophenol to gave an intermediate I, which on cyclisation

followed by oxidation yields desired product.

Ph H

O

K4[Fe(CN)6]

Ph H

OK4[Fe(CN)6]’’’’’’’’’’

oxidation

R

NH2

SHR

N

SH

Ph

R

NH

S

Ph

HR

II

N

SPh

..

-H2

....

NH2

OHR ..

oxidation

R

N

OH

Ph

R

NH

O

Ph

HR

II

N

OPh

..

-H2

..

Scheme 6. Proposed mechanism for the synthesis of benzoxazoles, benzothiazole


5.1.3.4 Conclusion:

In conclusion, simple, efficient, environmentally benign and high yielding protocol has

been developed via oxidation of Carbon-Nitrogen Bond for the synthesis of biologically active

benzoxazoles and benzothiazole derivatives using cheap, eco-friendly and water soluble catalyst

potassium ferro-cyanide. The great achievement of present protocol is the organic solvent-free

reaction conditions and it avoids the use of hazardous catalysts. These advantages make the

present method very effective for the synthesis of biological active benzoxazoles and

benzothiazole derivatives.

In conclusion, potassium ferro-cyanide was found to be a mild and efficient catalyst for

the formation of benzoxazoles and benzothiazoles. The use of this inexpensive, easily available

and reusable catalyst under solvent-free conditions makes this protocol practical,

environmentally friendly and economically attractive. The simple work-up procedure, mild

reaction conditions, very short reaction times, high yields of products and non-toxicity of the

catalyst are other advantages of the present method.

5.1.4 Experimental:

5.1.4.1 General procedure for the synthesis of benzoxazoles and benzothiazole in water media

A mixture of 2-aminophenol or 2-aminothiophenol (1 mmol), aldehyde (1 mmol) and

water (10 ml) were taken in a round bottom flask. To this mixture, potassium ferro-cyanide

(K4[Fe(CN6)], 10 mol %) was added and stirred at room temperature for given time period

(Table 1 & 2). After completion of the reaction (TLC) the solid obtained was filtered, washed

with water, dried and recrystallized from ethanol to obtain the desired product with excellent

yield.

5.1.4.2 General procedure for the synthesis of benzoxazoles and benzothiazole on grinding

A mixture of substituted 2-aminophenol or 2-aminothiophenol (1 mmol), aldehyde (1

mmol) and potassium ferro-cyanide (10 mol %) was crushed in a mortar with a pestle at room

temperature. Progress of reaction was monitored by TLC. After completion of reaction (< 2 min)

the crude product was washed with water, dried and recrystallized with ethanol.

5.1.5 Spectral data:

General experimental method

Melting points of the synthesized compounds were determined in open-glass capillaries on a

stuart-SMP10 melting point apparatus and are uncorrected. IR absorption spectra were recorded


on a Perkin Elmer 1650 FTIR using KBr pellets in the range of 4000-450 cm-1

.1H-NMRs were

recorded on a Bruker spectrometer operating at 300 MHz. The1H-NMR chemical shifts are

reported as parts per million (ppm) downfield from TMS (Me4Si) used as an internal standard.

The13

C NMR spectra were recorded at 50 MHz; chemical shifts (δ scale) are reported in parts

per million (ppm). Mass spectra were recorded on LCQ ion trap mass spectrometer. Purity of the

compounds were checked by thin layer chromatography (TLC) on Merck silica gel 60 F254 pre-

coated sheets in benzene/methanol mixture and spots were developed using iodine vapor as

visualizing agents.

2-phenyl-1,3-benzoxazole

N

O

99a

mp: 102oC;

IR: (KBr, cm-1

) ν 3019.50, 1634.07, 1526.79, 1453.36, 1225.91, 1054.34;

1H NMR: (CDCl3, 500 MHz), δ: 8.18 (d, 2H), 7.76-7.72 (m, 2H), 7.67-7.60 (m, 3H), 7.40-7.36

(d, 2H) ppm;

13C NMR: (CDCl3, 50 MHz,) δ: 161.41, 151.38, 138.47, 132.75, 128.61, 128.02, 127.77, 127.64,

124.33, 119.92, 110.59;

MS (ES): calcd for C13H9NO (M+) 195.21, found 195.10.

2-(4-methylphenyl)-1,3-benzoxazole

N

O

CH3

99c

mp: 112-114oC;

1H NMR: (CDCl3, 500 MHz), δ: 8.09-8.07 (d, 2H), 7.77 (t, 2H), 7.42-7.38 (m, 4H), 2.40 (s, 3H)

ppm;

13C NMR: (CDCl3, 50 MHz,) δ: 161.41, 151.38, 141.57, 138.47, 129.04, 127.64, 126.48, 124.33,

119.42, 110.59, 21.53;

MS (ES): calcd for C14H11NO (M+) 209.24, found 209.16.


2-(4-chlorophenyl)-1,3-benzoxazole

N

O

Cl

99d

mp: 148-151oC;

1H NMR: (CDCl3, 500 MHz), δ: 8.23-8.25 (d, 2H), 7.54-7.56 (d, 2H), 7.81-7.82 (m, 1H), 7.62,

7.64 (m, 1H), 7.40-7.42 (m, 2H) ppm;

13C NMR: (CDCl3, 50 MHz,) δ: 161.41, 151.38, 138.47, 137.26, 129.29, 128.29, 127.64, 124.33,

119.92, 110.59;

MS (ES): calcd for C13H8ClNO (M+) 229.66, found 229.46.

5-(5-chloro-1,3-benzoxazol-2-yl)-2-methoxyphenol

N

O

Cl

OH

OCH3

99h

mp: 142-144oC;

1H NMR: (CDCl3, 500 MHz), δ: 7.81 (s, 1H), 7.75 (d, 1H), 7.58 (d, 1H), 7.40 (d, 1H), 7.18 (s,

1H), 6.83 (d, 1H), 5.58 (s, 1H), 3.86 (s, 3H) ppm;

13C NMR: (CDCl3, 50 MHz,) δ: 161.50, 152.42, 150.01, 149.36, 137.83, 129.09, 126.33, 120.36,

120.08, 117.43, 115.03, 111.71, 111.42, 56.83;

MS (ES): calcd for C14H10ClNO3 (M+) 275.68, found 275.40.

5-chloro-2-phenyl-1,3-benzoxazole

N

O

Cl

99i

mp: 110-113oC;

1H NMR: (CDCl3, 500 MHz), δ: 8.30-8.32 (d, 2H), 7.62 (s, 1H), 7.55-7.57 (m, 3H), 7.49-7.50

(d, 1H), 7.20-7.21 (d, 1H) ppm;

13C NMR: (CDCl3, 50 MHz,) δ: 161.53, 150.01, 137.83, 132.75, 129.09, 128.02, 127.77, 126.33,

117.43, 111.70;

MS (ES): calcd for C13H8ClNO (M+) 229.66, found 229.40.


2-(4-methylphenyl)-5-nitro-1,3-benzoxazole

N

O

O2N

CH3

99j

mp: 192-194oC;

1H NMR: (DMSO-d6, 500 MHz), δ: 8.58 (d, 1H), 7.85 (m, 1H), 7.78 (d, 2H), 7.30 (m, 1H), 7.23

(m, 2H), 2.40 (d, 3H) ppm;

13C NMR: (CDCl3, 50 MHz,) δ: 161.48, 151.33, 141.57, 141.24, 139.44, 129.04, 126.35, 120.79,

119.21, 110.92, 21.10;

MS (ES): calcd for C14H10N2O3 (M+) 254.24, found 254.18.

2-phenyl-1,3-benzothiazole

N

S

102a

mp:oC; 112-113;

IR: (KBr, cm-1

) ν ; 3246.73, 2923.64, 1507.77;

1H NMR: (CDCl3, 500 MHz), δ: 8.18 (d, 1H), 8.05-8.01 (m, 3H), 7.55-7.49 (m, 5H) ppm;

13C NMR: (CDCl3, 50 MHz,) δ: 166.61, 151.77, 136.02, 134.89, 132.14, 129.31, 127.28, 126.29,

126.04, 123.49, 123.18;

MS (ES): calcd for C13H9NS (M+) 211.28, found 212.20

2-(4-methylphenyl)-1,3-benzothiazole

N

S

CH3

102b

mp:oC; 118-119

1H NMR: (CDCl3, 500 MHz), δ: 8.29–7.18 (m, 8H), 2.64 (s. 3H) ppm;

13C NMR: (CDCl3, 50 MHz,) δ: 166.61, 151.77, 139.03, 136.02, 132.73, 129.26, 127.89, 126.04,

123.49, 123.18, 21.24;

MS (ES): calcd for C14H11NS (M+) 225.30, found 225.20


4-(1,3-benzothiazol-2-yl)phenol

N

S

OH

102d

mp:oC; 225-227;

IR: (KBr, cm-1

) ν 3404.14, 2928.27, 2845.32, 1626.86, 1491.60, 1021.10;

1H NMR: (CDCl3, 500 MHz), δ: 8.18 (d, 1H), 8.02 (d, 1H), 7.73 (d, 2H), 7.55-7.49 (m, 2H),

6.86 (d, 2H), 5.13 (s, 1H) ppm;

13C NMR: (CDCl3, 50 MHz,) δ: 166.61, 161.37, 151.77, 136.02, 129.98, 126.29, 126.04, 123.56,

123.49, 123.18, 116.70;

MS (ES): calcd for C13H9NOS (M+) 227.28, found 227.17

2-[3-fluoro-4-(trifluoromethyl)phenyl]-1,3-benzoxazole

N

O

CF 3

F

105e

Sticky Semi-solid

IR: (KBr, cm-1

) ν 3253.19, 2923.60, 1641.42, 1501.51, 1258.21, 1134.63, 1019.10;

1H NMR: (CDCl3, 500 MHz), δ: 7.76-7.69 (m, 3H), 7.61 (d, 1H), 7.40-7.36 (m, 2H) ppm;

13H NMR: (50 MHz, CDCl3), δ: 162.72, 162.69, 162.66, 161.48, 160.68, 160.61, 151.3, 138.47,

132.99, 132.93, 128.12, 127.64, 125.07, 124.33, 121.73, 119.63;

MS (ES): calcd for C14H7F4NO (M+) 281.20, found 281.10

5-chloro-2-(4-nitrophenyl)-1,3-benzoxazole

N

O

NO2

Cl

105g

Sticky Semi-solid

IR: (KBr, cm-1

) ν 3025.54, 2871.9, 1641.32, 1503.51, 1134.63, 1020.10, 748.10;

1H NMR: (CDCl3, 500 MHz), δ: 8.34 (d, 2H), 8.22 (d, 2H), 7.81 (s, 1H), 7.75 (d, 1H), 7.40 (d,

1H) ppm;


13H NMR: (50 MHz, CDCl3), δ: 161.53, 150.01, 148.95, 137.83, 134.59, 129.09, 128.93,

126.33, 124.19, 117.43, 111.71;

MS (ES): calcd for C13H7ClN2O3 (M+) 274.65, found 274.40

5-chloro-2-[3-fluoro-4-(trifluoromethyl)phenyl]-1,3-benzoxazole

N

O

CF3

F

Cl

105h

Sticky Semi-solid

1H NMR: (CDCl3, 500 MHz), δ: 7.15-7.49 (m, 6H) ppm;

13H NMR: (50 MHz, CDCl3), δ: 160.4, 151.6, 148.1, 141.5, 130.7, 127.4, 122.9, 120.9, 118,

114.3, 112.2, 108.5

MS (ES): calcd for C14H6ClF4NO (M+) 315.65 found 315.38

2-(2-chlorophenyl)-1,3-benzothiazole

N

S

Cl

108g

mp: 70-72oC;

1H NMR: (CDCl3, 500 MHz), δ: 8.18 (d, 1H), 8.02 (d, 1H), 7.74 (d, 1H), 7.55-7.49 (m, 3H),

7.40-7.34 (m, 2H) ppm;

13H NMR: (50 MHz, CDCl3), δ: 166.06, 151.77, 136.02, 133.84, 132.30, 131.34, 129.96,

128.17, 128.07, 126.29, 126.04, 123.49, 123.18;

MS (ES): calcd for C13H8ClNS (M+) 245.72, found 247.2

2-[3-fluoro-4-(trifluoromethyl)phenyl]-1,3-benzothiazole

N

S

F

CF3

108h


mp: 184-186oC;

1H NMR: (CDCl3, 500 MHz), δ: 8.13 (s, 1H, Ar–H), 8.11 (d, 1H, J = 8.5 Hz, Ar–H), 7.95 (d,

1H, J = 8 Hz, Ar–H), 7.27–7.53 (m, 4H, Ar–H) ppm;

13H NMR: (50 MHz, CDCl3), δ: 165.67, 163.36, 161.37, 161.31, 151.77, 141.46, 141.40,

136.02, 128.54, 126.04, 125, 124.75, 123.88, 121.77, 121.24, 121.10, 119.63, 119.59;


2-(4-nitrophenyl)-1,3-benzothiazole

N

S

NO2

108i

mp:oC; 229-231

IR: (KBr, cm-1

) ν 3120.46, 1622.97, 1595.78, 1470.85, 1188.49;

1H NMR: (CDCl3, 500 MHz), δ: 8.27 (d, 2H), 8.18 (s, 1H), 8.12 (d, 2H), 8.02 (d, 1H), 7.55-7.49

(m, 2H) ppm;

13H NMR: (50 MHz, CDCl3), δ: 166.61, 15.77, 148.93, 142.33, 136.02, 127.78, 126.29, 126.04,

124.87, 123.49, 123.18;


5.1.6 Spectra’s

5.1.6.1 Spectra’s of 2-phenyl-1,3-benzoxazole (99a)


5.1.6.2 Spectra’s of 5-(5-chloro-1,3-benzoxazol-2-yl)-2-methoxyphenol (99h)


5.1.6.3 Spectra’s of 2-phenyl-1,3-benzothiazole (102a)


5.1.6.4 Spectra’s of 4-(1,3-benzothiazol-2-yl)phenol (102d)


5.1.6.5 Spectra’s of 2-[3-fluoro-4-(trifluoromethyl)phenyl]-1,3-benzoxazole (105e)


5.1.6.6 Spectra’s of 5-chloro-2-(4-nitrophenyl)-1,3-benzoxazole (105g)


5.1.6.7 Spectra’s of 2-(2-chlorophenyl)-1,3-benzothiazole (108g)


5.1.6.8 Spectra’s of 2-(4-nitrophenyl)-1,3-benzothiazole (108i)


5.1.7 References:

1. Chaney, M. O.; Demarco, P. V.; Jones, N. D.; Occolowitz, J. L. J. Am. Chem. Soc. 1974,

96, 1932.

2. Sato, S.; Kajiura, T.; Noguchi, M.; Takehana, K.; Kobayasho, T.; Tsuji, T. J. Antibiot.

2001, 54, 102.

3. Brown, R. N.; Cameron, R.; Chalmers, D. K.; Hamilton, S.; Luttick, A.; Krippner, G. Y.;

McConnell, D. B.; Nearn, R.; Stanislawski, P. C.; Tucker, S. P.; Watson, K. G. Bioorg.

Med. Chem. Lett. 2005, 15, 2051;

4. Manas, E. S.; Unwalla, R. J.; Xu, Z. B.; Malamas, M. S.; Miller, C. P.; Harris, H. A.;

Hsiao, C.; Akopian, T.; Hum, W.-T.; Malakian, K.; Wolfrom, S.; Bapat, A.; Bhat, R. A.;

Stahl, M. L.; Somers, W. S.; Alvarez, J. C. J. Am. Chem. Soc. 2004, 126, 15106.

5. Malamas, M. S.; Manas, E. S.; McDevitt, R. E.; Gunawan, I.; Xu, Z. B.; Collini, M. D.;

Miller, C. P.; Dinh, T.; Henderson, R. A.; Keith, J. C., Jr.; Harris, H. A. J. Med. Chem.

2004, 47, 5021.


6. Prudhomme, M.; Guyot, J.; Jeminet, G. J. Antibiotics 1986, 39, 934–937.

7. O¨ ren, I˙.; Temiz, O¨ .; Yalçin, I˙.; S¸ ener, E.; Akin, A.; Uçartu¨ rk, N. Arzneim

Forsch. Drug. Res. 1997, 47, 1393–1397.

8. O¨ ren, I˙.; Temiz, O¨ .; Yalçin, I˙.; Aki-S¸ ener, E.; Altanlar, N. Eur. J. Pharm. Sci.

1999, 7, 153–160.

9. Temiz-Arpaci, O.; Ozdemir, A.; Yalcin, I.; Yildiz, I.; Aki-Sener, E.; Altanlar, N. Arch.

Pharm. 2005, 338, 105–111.

10. Vinsova, J.; Horak, V.; Buchta, V.; Kaustova, J. Molecules 2005, 10, 783–793.

11. Song, X.; Vig, B. S.; Lorenzi, P. L.; Drach, J. C.; Townsend, L. B.; Amidon, G. L. J.

Med. Chem. 2005, 48, 1274–1277.

12. Pinar, A.; Yurdakul, P.; Yildiz, I.; Temiz-Arpaci, O.; Acan, N. L.; Aki-Sener, E.; Yalcin,

I. Biochem. Biophys. Res. Commun. 2004, 317, 670–674.

13. Ueki, M.; Taniguchi, M. J. Antibiotics 1997, 50, 788–790.

14. McKee, M. L.; Kerwin, S. M. Bioorg. Med. Chem. 2008, 16, 1775.

15. Oksuzoglu, E.; Temiz-Arpaci, O.; Tekiner-Gulbas, B.; Eroglu, H.; Sen, G.; Alper, S.;

Yildiz, I.; Diril, N.; Aki-Sener, E.; Yalcin, I. Med. Chem. Res. 2008, 16, 1.

16. Gong, B.; Hong, F.; Kohm, C.; Bonham, L.; Klein, P. Bioorg. Med. Chem. Lett. 2004, 14,

1455.

17. Sun, L.-Q.; Chen, J.; Bruce, M.; Deskus, J. A.; Epperson, J. R.; Takaki, K.; Johnson, G.;

Iben, L.; Mahle, C. D.; Ryan, E.; Xu, C. Bioorg. Med. Chem. Lett. 2004, 14, 3799.

18. Ertan, T.; Yildiz, I.; Tekiner-Gulbas, B.; Bolelli, K.; Temiz-Arpaci, O.; Yalcin, I.; Aki,

E.; Ozkan, S.; Kaynak, F. Eur. J. Med. Chem. 2009, 44, 501.

19. Alper-Hayta, S.; Arisoy, M.; Temiz-Arpaci, O.; Yildiz, I.; Aki, E.; Oezkan, S.; Kaynak,

F. Eur. J. Med. Chem. 2008, 43, 2568.

20. Tekiner-Gulbas, B.; Temiz-Arpaci, O.; Yildiz, I.; Altanlar, N. Eur. J. Med. Chem. 2007,

42, 1293.

21. Yildiz-Oren, I.; Tekiner-Gulbas, B.; Yalcin, I.; Temiz-Arpaci, O.; Aki-Sener, E.;

Altanlar, N. Arch. Pharm. 2004, 337, 402.

22. Sun, A.; Prussia, A.; Zhan, W.; Murray, E. E.; Doyle, J.; Cheng, L.-T.; Yoon, J. J.;

Radchenko, E. V.; Palyulin, V. A.; Compans, R. W.; Liotta, D. C.; Plemper, R. K.;

Snyder, J. A. J. Med. Chem. 2006, 49, 5080.


23. Beneteau V, Besson T, Guillard J, Leonce S, Pfeiffer B. Eur. J. Med. Chem. 1999; 34,

1053-60.

24. Wells, G.; Bradshaw, T. D.; Diana, P. Bioorg. & Med. Chem. Letters. 2000; 10, 513-15.

25. Shi, D.; Bradshaw, T. D.; Chua, M.; Westwell, A. D.; Stevens, M. F. G. Bioorg. & Medi.

Chem. 2001, 11, 1093-5.

26. Hutchinson, I.; Bradshaw, T. D.; Matthews, C. S.; Stevens, M. F. G.; Westwell, A. D.

Bioorg. & Med. Chem. Letters 2003, 13, 471-4.

27. Yalcin, I.; Oren, I.; Sener, E.; Akin, A.; Ucarturk, N. Eur. J. Med. Chem. 1992, 27, 401-6.

28. Gurupadayya, B. M.; Gopal, M.; Padmashali, B.; Vaidya, V. P. International J.

Heterocyclic chem. 2005, 15, 169-72.

29. Latrofa, A.; Franco, M.; Lopedota, A.; Rosato, A.; Carone, D.; Vitali, C. I L Farmaco.

2005, 60, 291-7.

30. Palmer, F. J.; Trigg, R. B.; Warrington, J. V. J. Med. Chem. 1971, 14, 248-51.

31. Burger, A.; Sawhey, S. N. J. Med. Chem. 1968, 11, 270-73.

32. Alam, M.; Siddiqui, N. Indian J. Heterocyclic Chem. 2004, 13, 361-4.

33. Chakole, R. D.; Amnerkar, N. D.; Khedekar, P. B.; Bhusari, K. P. Indian J. Heterocyclic

Chem. 2005; 15: 27-30.

34. Jayachandran, E.; Bhatia, K.; Naragud, L. V. G.; Roy, A. Indian Drugs. 2003, 40, 408-

11.

35. Siddiqui, N.; Alam, M.; Siddiqui, A. A. Asian J. Chem. 2004, 16, 1005- 8.

36. Gurupadayya, B. M.; Gopal, M.; Padmashali, B.; Vaidya, V. P. International J.

Heterocyclic chem. 2005, 15, 169-72.

37. Lee, C. L.; Lam, Y.; Lee, S. Tetrahedron Letters. 2001, 42, 109-11.

38. Nagel, A. A.; Liston, D. R.; Jung, S.; Maher, M.; Vincent, L. A.; Chapin, D.; Chen, Y. L.;

Hubbard, S.; Ives, J. L.; Jones, S. B. J. Med. Chem. 1995, 38, 1084;

39. Deluca, M. R.; Kerwin, S. M. Tetrahedron Lett. 1997, 38, 199;

40. Temiz, O.; Oren, I.; Sener, E.; Yalcin, I.; Ucarturk, N. Farmaco 1998, 53, 337;

41. Sato, S.; Kajiura, T.; Noguchi, M.; Takehana, K.; Kobayashi, T.; Tsuji, T. J. Antibiot.

2001, 54, 102;

42. Sondhi, S. M.; Singh, N.; Kumar, A.; Lozach, O.; Meijer, L. Bioorg. Med. Chem. 2006,

14, 3758–3765;


43. Vinsova, J.; Cermakova, K.; Tomeckova, A.; Ceckova, M.; Jampilek, J.; Cermak, P.;

Kunes, J.; Dolezal, M.; Staud, F. Bioorg. Med. Chem. 2006, 14, 5850–5865;

44. Gong, B.; Hong, F.; Kohm, C.; Bonham, L.; Klein, P. Bioorg. Med. Chem. Lett. 2004,

14, 1455–1459.

45. Speier G. Journal of Molecular Catalysis 1987, 41, 253-260.

46. Poissonnet G. Synthetic Comm. 1997, 27, 3839-3846.

47. Varma, R. S.; Saini, R. K.; Prakash, O. Tetrahedron Letters 1997, 38, 2621-2622.

48. Ying-Hung, S.; DeCaire, R.; Synthetic Comm. 1998, 28, 4123-4135.

49. Loupy, A.; Regnier, S. Tetrahedron Letters 1999, 40, 6221-6224.

50. Saitz, C.; Rodr´ıguez, H.; M´arquez, A.; Ca˜ nete, A.; Jullian, C.; Zanocco, A. Synthetic

Comm. 2001, 31, 135-140.

51. Chang, J.; Zhao, K.; Pan, S. Tetrahedron Letters 2002, 43, 951–954.

52. Pottorf, R. S.; Chadha, N. K.; Katkevics, M.; Ozola, V.; Suna, E.; Ghane, H.; Regberg,

T.; Player, M. R. Tetrahedron Letters 2003, 44, 175-178.

53. Matsushita, H.; Lee, S.-H.; Joung, M.; Clapham, B.; Janda, K. D. Tetrahedron Letters

2004, 45, 313-316.

54. Nadaf, R. N.; Siddiqui, S. A.; Daniel, T.; Lahoti, R. J.; Srinivasan, K. V. Journal of

Molecular Catalysis A: Chemical 2004, 214, 155-160.

55. Wang, Y.; Sarris, K.; Sauer, D. R.; Djuric, S. W. Tetrahedron Letters 2006, 47, 4823-

4826.

56. Moghaddam, F. M.; Bardajee, G. R.; Ismaili, H.; Taimoory, S. M. D. Synthetic Comm.

2006, 36, 2543–2548.

57. Spatz, J. H.; Bach, T.; Umkehrer, M.; Bardin, J.; Ross, G.; Burdack, C.; Kolb, J.

Tetrahedron Letters 2007, 48, 9030–9034.

58. Mohammadpoor-Baltork, I.; Khosropour, A. R.; Hojati, S.F. Catalysis Communications

2007, 8, 1865–1870.

59. Kaul, S.; Kumar, A.; Sain, B.; Bhatnagar, A. K. Synthetic Comm. 2007, 37, 2457–2460.

60. Radi, M.; Saletti, S.; Botta, M. Tetrahedron Letters 2008, 49, 4464–4466.

61. Costa, S. P. G.; Oliveira, E.; Lodeiro, C.; Raposo, M. M. M. Tetrahedron Letters 2008,

49, 5258–5261.


62. Shoar, R. H.; Heidary, M.; Farzaneh, M.; Malakouti, R. Synthetic Comm. 2009, 39,

1742–1751.

63. Blacker, A, J,; Farah, M. M.; Marsden, S. P.; Saidi, O.; Williams, J. M. J. Tetrahedron

Letters 2009, 50, 6106–6109.

64. Chen, W.-H.; Pang, Y. Tetrahedron Letters 2009, 50, 6680–6683.

65. Patil, S. S.; Bobade, V. D. Synthetic Comm. 2010, 40, 206-212.

66. Srivani, A.; Venkateswar Rao, K. T.; Sai Prasad, P. S.; Lingaiah, N. Journal of Molecular

Catalysis A: Chemical 2010, 328, 119-123.

67. Tao, K.; Zheng, J.; Liu, Z.; Shen, W.; Zhang, J. Tetrahedron Letters 2010, 51, 3246–

3249.

68. Reyes, H.; Beltran, H. I.; Rivera-Becerril, E. Tetrahedron Letters 2011, 52, 308–310.

69. Chen, F.; Shen, C.; Yang, D. Tetrahedron Letters 2011, 52, 2128–2131.

70. Riadi, Y.; Mamouni, R.; Azzalou, R.; Haddad, M. E.; Routier, S.; Guillaumet, G.; Lazar,

S. Tetrahedron Letters 2011, 52, 3492–3495.

71. López-Ruiz, H.; Briseño-Ortega, H.; Rojas-Lima, S.; Santillan, R.; Farfán, N.

Tetrahedron Letters 2011, 52, 4308–4312.

72. Madhusudana Reddy, M. B.; Nizam, A.; Pasha, M. A. Synthetic Comm. 2011, 41, 1838–

1842.

73. Bachhav, H. M.; Bhagat, S. B.; Telvekar, V. N.; Tetrahedron Letters 2011, 52, 5697–

5701.

74. Wen, X.; Bakali, J. E.; Deprez-Poulain, R.; Deprez, B. Tetrahedron Letters 2012, 53,

2440-2443.

75. Shi, D.-F.; Bradshaw, T. D.; Wrigley, S.; McCall, C. J.; Lelieveld, P.; Fichtner, I.;

Stevens, M. F. G. J. Med. Chem. 1996, 39, 3375–3384.

76. Beebe, X.; Wodka, D.; Sowin, T. J. J. Comb. Chem. 2001, 3, 360–366.

77. Hari, A.; Karan, C.; Rodrigues, W. C.; Miller, B. L. J. Org. Chem. 2001, 66, 991–996.

78. Pottorf, R. S.; Chadha, N. K.; Katkevics, M.; Ozola, V.; Suna, E.; Ghane, H.; Regberg,

T.; Player, M. R. Tetrahedron Lett. 2003, 44, 175–178.

79. Chen, F.; Shen, C.; Yang, D. Tetrahedron Lett. 2011, 52, 2128–2131.

80. Chua, M.-S.; Shi, D.-F.; Wrigley, S.; Bradshaw, T. D.; Hutchinson, I.; Shaw, P. N.;

Barrett, D. A.; Stanley, L. A.; Stevens, M. F. G. J. Med. Chem. 1999, 42, 381–392.


81. Kashiyama, E.; Hutchinson, I.; Chua, M.-S.; Stinson, S. F.; Phillips, L. R.; Kaur, G.;

Sausville, E. A.; Bradshaw, T. D.; Westwell, A. D.; Stevens, M. F. G. J. Med. Chem.

1999, 42, 4172–4184.

82. Hutchinson, I.; Chua, M.-S.; Browne, H. L.; Trapani, V.; Bradshaw, T. D.; Westwell, A.

D.; Stevens, M. F. G. J. Med. Chem. 2001, 44, 1446–1455.

83. Leng, W.; Zhou, Y.; Xu, Q.; Liu, J. Macromolecules 2001, 34, 4774–4779.

84. Hutchinson, I.; Jennings, S. A.; Vishnuvajjala, B. R.; Westwell, A. D.; Stevens, M. F. G.

J. Med. Chem. 2002, 45, 744–747.

85. Blacker, A. J.; Farah, M. M.; Hall, M. I.; Marsden, S. P.; Saidi, O.; Williams, J. M. Org.

Lett. 2009, 11, 2039–2042.

86. Shi, D. F.; Bradshaw, T. D.; Wrigley, S.; McCall, C. J.; Lelieveld, P.; Fichtner, I.;

Stevens, M. F. J. Med. Chem. 1996, 39, 3375–3384.

87. Tandon, V. K.; Kumar, M. Tetrahedron Lett. 2004, 45, 4185–4187.

88. Charton, J.; Girault-Mizzi, S.; Sergheraert, C. Chem. Pharm. Bull. 2005, 53, 492–497.

89. Seijas, J. A.; Vazquez, T.; Pilar, M.; Carballido, R.; Raquel, M.; Crecente, C. J.; Romar-

Lopez, L. Synlett 2007, 313–317.

90. Maradolla, M. B.; Allam, S. K.; Mandha, A.; Chandramouli, G. V. P. Arkivoc 2008, XV,

42–46.

91. Raghavendra, G. M.; Ramesha, A. B.; Revanna, C. N.; Nandeesh, K. N.; Mantelingu, K.;

Rangappa, K. S. Tetrahedron Lett. 2011, 52, 5571–5574.

92. Laszlo, C.; Werner, F.; Bernhard, K.; Ursula, H.; Johannes, F.; Ulrich, J. Tetrahedron

Letters. 1998, 39, 2087-2088.

93. Grego, G.; Luucia, P.; Alessandra, N.; Marco, D. Tetrahedron Letters. 2009, 50, 3095-

3097.

94. Xiao, Z. Y.; Ji, D. G. Journal of Harzardous materials. 2008, 156, 300-307.

95. Gaffar, M. A.; A-Abu-El, dl. Physica B. 2000, 292, 221-232.


List of Publications and communicated papers

1) An efficient solvent free synthesis of meso-substituted dipyrromethanes from lowest

pyrrole/aldehyde ratio on grinding. . K. A. Shaikh, Vishal A. Patil Asian Journal of

Reserch in Chemistry. 2011, 4, 1408-1410

2) Mechanostic Synthesis of 1,5-benzodiazepines using molecular Iodine. Shaikh K.

Ahmed, Arshia Parveen, Vishal A. Patil. International Journal of Industrial

Chemistry. 2011, 2, 144-153.

3) An efficient solvent-free synthesis of Imidazolines and Benzimidazoles using

K4[Fe(CN)6] catalysis. K. A. Shaikh, Vishal A. Patil. Organic Commun. 2012, 5:1,

12-17.

4) A Novel method for the synthesis of dipyrromethanes under solvent-free condition.

K. A. Shaikh, Vishal A. Patil, Azeem Ahmed, E-Journal of Chemistry. 2012, 9(4),

1796-1800

5) An efficient solvent free synthesis and Anti-bacterial activity of Novel hydrazones

derived from 4,5-diazafluoren-9-hydrazone on grinding. K. A. Shaikh, Vishal A.

Patil, Azeem Ahmed, Asian Journal of Chemistry. 2012, 24(7), 2951-2956.

6) An Efficient and Convenient Synthesis of Imidazolines and Benzimidazoles via

Oxidation of Carbon-Nitrogen Bond in Water Media. Shaikh, Kabeer A., Patil,

Vishal A., Parveen Arshia. Chines Journal of Chemistry, 2012, 30(4), 924-928.

7) An environmentally benign, solvent free synthesis and antibacterial activity of Novel

Schiff bases derived from 4,5-diazafluoren-9-one. K. A. Shaikh, Vishal A. Patil.

Azeem Ahmed. Elixir Org. Chem. 2012, 45, 7881-7883.

8) Solid phase-promoted greener synthesis and antibacterial activity of Novel Schiff

bases under catalytically free condition. . K. A. Shaikh, Vishal A. Patil. Zamir A.

Mohammed. Elixir Org. Chem. 2012, 43, 6960-6963.

9) Atom efficient grinding technique for the synthesis of hydrazones catalyzed by citric

acid, Mohammed Zamir Ahmed, N. T. Patel, K. A. Shaikh, M. A. Baseer, Shaikh

Shahid and Vishal A. Patil, Elixir Org. Chem. 2012, 43, 6583-6585.


10) SnCl2.2H2O; a precious addition to catalyst range for synthesis of bis (indolyl)

methanes. K. A. Shaikh, Z. A. Mohammed, N. T. Patel, Vishal A. Patil. Research

Journal of Pharmaceutical, Biological and Chemical Sciences. 2010, 1, 730-736.

11) SnCl2·2H2O catalyzed solid phase synthesis of meso-substituted dipyrromethanes, K.

A. Shaikh, Vishal A. Patil, B. P. Bandgar. Orbital. (Accepted for publication)

12) Rapid and solvent free synthesis of synthesis of Benzoxazoles and Benzthiazoles by

using K4[Fe(CN)6] as an efficient catalysis. K. A. Shaikh, Vishal A. Patil, Organic

Commun. (Communicated)

13) Efficient synthesis of hydrazones by mechanochemistry (grinding) under solvent free

condition. K. A. Shaikh, Vishal A. Patil, Arshia Parveen. Green Chem. Lett. And

Review. (Communicated)

14) Greener synthesis of Benzoxazoles and Benzthiazoles by using K4[Fe(CN)6]

catalysis, K. A. Shaikh, Vishal A. Patil, B. P. Bandgar. Tetrahedron Lett.,

(Communicated)

Conferences Attended National/International

1) The paper entitled “An environmentally benign, solvent free synthesis and

antibacterial activity of Novel Schiff bases derived from 4,5-diazafluoren-9-one”

was presented in “National Conference on Advanced Tools in Chemical Analysis

organized by Department of Chemistry, Deogiri College, Aurangabad on 26th

and

27th

Aug. 2011.

2) The paper entitled “An efficient solvent free synthesis of meso-substituted

dipyrromethanes from lowest pyrrole/aldehyde ratio on grinding” was presented

in “National Conference on Advanced Tools in Chemical Analysis” organized by

Department of Chemistry, Deogiri College, Aurangabad on 26th

and 27th

Aug. 2011.

3) The paper entitled “SnCl2 2H2O a precious addition in catalyst range for

synthesis of 1,5-benzodiazepines” was presented in “National Conference on

Advanced Tools in Chemical Analysis” organized by Department of Chemistry,

Deogiri College, Aurangabad on 26th

and 27th

Aug. 2011.


4) The paper entitled “Potassium ferro-cyanide catalyzed an efficient and

convenient synthesis of benzoxazoles and benzothiazoles” was presented in “17th

International Conference on Expanding Horizons in Chemical and Biological

Science: Innovations Crossroads” organized by School of Chemical Sciences,

Solapur University, Solapur on 21st-24

thJanuary 2012.

5) The paper entitled “Stannous Chloride as an efficient catalyst for the synthesis of

1,5-benzodiazepine derivatives under solvent free conditions” was presented in

“17th

International Conference on Expanding Horizons in Chemical and

Biological Science: Innovations Crossroads” organized by School of Chemical

Sciences, Solapur University, Solapur on 21st-24

thJanuary 2012.

The paper entitled “Potassium ferro-cyanide catalyzed highly rapid synthesis of

benzoxazoles and benzothiazoles under solvent free condition” was presented in

“17th

International Conference on Expanding Horizons in Chemical and

Biological Science: Innovations Crossroads” organized by School of Chemical

Sciences, Solapur University, Solapur on 21st-24

thJanuary 2012.

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