chapter 5shodhganga.inflibnet.ac.in/.../39780/10/10_chapter5.pdf · 2018-07-02 · chapter-5 198...

CHAPTER – 5

One Pot Microwave Assisted

Synthesis, Characterization and

Antimicrobial Activity of Novel

Benzochromene Derivatives

Bearing Pyrazole Moiety

Chapter-5

196

5.1 Introduction

The environmental laws generated new ways of thinking about chemical

safety and the environmental aspects of chemicals. It was recognized that chemistry is

one of the key sciences in taking care of the environmental problems created by

chemicals. Solvent usage is often an integral part of a chemical or manufacturing

process. The unavoidable choice of a specific solvent for a desired chemical reaction

can have profound economical, environmental, and societal implications. The

pressing need to develop alternative solvents to some extent originates from these

implications and constitutes an essential strategy under the emerging field of green

chemistry1-4

. Green chemistry defined as the “Approach to synthesis, processing and

use of chemicals that reduces risks to humans and the environment”. Toward this end,

considerable efforts have been devoted to develop and use nontraditional solvents for

chemical synthesis5. Such unconventional media include, among others, solvent-free

conditions6, supercritical carbon dioxide

7, ionic liquids

8, perfluorinated solvents

9, and

last but not least water10, 11

. There is widespread current debate over the relative

“greenness” of these individual reaction media, but water can undoubtedly be

considered the cleanest solvent available, and the use and release of clean water

clearly will have the least impact to the environment12

.

On the other hand, for many chemical processes a major adverse effect to the

environment is the consumption of energy for heating and cooling. To overcome these

problems it is highly desirable to develop efficient methods that use alternative energy

sources such as ultrasound or microwave irradiation to facilitate chemical reactions.

In particular, the use of microwave energy to directly heat chemical reactions has

become an increasingly popular technique in the scientific community13,14

.

Microwave synthesis represents a major breakthrough in synthetic chemistry

methodology, a dramatic change in the way chemical synthesis is performed and in

the way it is perceived in the scientific community. Conventional heating, long known

to be inefficient and time–consuming, has been recognized to be creatively limiting as

well. Microwave synthesis gives organic chemists more time to expand their scientific

creativity, test new theories and develop new processes. Instead of spending hours or

even days synthesizing a single compound, chemists can now perform that same

reaction in minutes. In concert with rapidly expanding application base, microwave

Chapter-5

197

synthesis can be effectively applied to any reaction scheme, creating faster reactions,

improving yields and producing cleaner chemistries.

In addition, microwave synthesis creates completely new possibilities in

performing chemical transformations. Because microwaves can transfer energy

directly to the relative species, so-called “molecular heating”, they can promote

transformations that are currently not possible using conventional heat. This is

creating a new realm in synthetic organic chemistry.

Microwaves also provide chemists with the option to perform “cool

reactions”. Energy is applied directly to reactants. However, the bulk heating is

minimized by use of simultaneous cooling. This allows for enhanced reactions of

larger, more heat sensitive molecules (e.g. proteins), as the temperatures are low

enough to eliminate thermal degradation. This will provide some exciting new

opportunities and an important new tool for proteomics and genomics research.

Recent microwave hardware advancements now provide a range of affordable,

flexible tools for the synthetic chemist. This new technology, coupled with the rapidly

expanding knowledge and applications base, will cause a major shift towards

microwave synthesis in the next few years. As Victor Hugo, the famous French

novelist and poet wrote, “An invasion of armies can be resisted, but not an idea whose

time has come”. Microwave synthesis is an idea whose time has come and whose

impact will be truly monumental on the world of chemistry.

The development of microwave technology was stimulated by World War II,

when the magnetron was designed to generate fixed frequency microwaves for

RADAR devices15,16

. Percy LeBaron Spencer of the Raytheon Company accidentally

discovered that microwave energy could cook food when a candy bar in his pocket

melted while he was experimenting with radar waves. Further investigation showed

that microwaves could increase the internal temperature of foods much quicker than a

conventional oven. This ultimately led to the introduction of the first commercial

microwave oven for home use in 1954.

Investigation into the industrial applications for microwave energy also began

in the 1950s and has continued to the present. Microwave energy has found many

uses including irradiating coal to remove sulfur and other pollutants, rubber

vulcanization, product drying, moisture and fat analysis of food products, and solvent

extraction applications. Wet ashing or digestion procedures for biological and

geological samples have also become very important analytical tools. As

Chapter-5

198

improvements and simplifications were made in magnetron design, the process of

domestic ovens fell significantly. Consequently, research done in the latter half of the

20th

century was performed in modified domestic microwave ovens. The effects of

microwave irradiation in organic synthesis were not explored until the mid 1980s. The

first two papers on microwave enhanced organic chemistry were not published in

1986 and many organic chemists have since discovered the benefits of using

microwave energy to drive synthetic reactions17

. Until recently, most of this research

has been executed in multimode domestic microwave ovens, which have proven to be

problematic. These ovens are not designed for the rigors of laboratory usage: acids

and solvents corrode the interiors quickly; there are no safety controls, temperature or

pressure monitoring and the cavities are not designed to withstand the resulting

explosive force from a vessel failure in run away reactions.

In the 1980s, companies began to address these issues by manufacturing

industrial microwave ovens specifically designed for use in laboratories. These

multimode systems featured corrosion resistant stainless steel cavities with reinforced

doors, temperature and pressure monitoring, and automatic safety controls. They have

worked well for doing large scale laboratory applications, but they have some

fundamental limitations in performing small scale synthetic chemistry. Recently,

single mode technology, which provides more uniform and concentrated microwave

power, has become available. These newer systems represent a breakthrough in

providing new capabilities for doing microwave synthesis and are a de factor in the

rapid expansion of this field of science.

Microwaves are a powerful, reliable energy source that may be adapted to

many applications. Understanding the basic theory behind microwaves will provide

the organic chemist with the right tools and knowledge to be able to effectively apply

microwave energy to any synthetic route.

A microwave is a form of electromagnetic energy that falls at the lower

frequency end of the electromagnetic spectrum, and is defined in the 300 to about

300,000 megahertz (MHz) frequency range. Within this region of electromagnetic

energy, only molecular rotation is affected, not molecular structure. Out of four

available frequencies for industrial, scientific, or medical applications, 2450MHz is

preferred because it has the right penetration depth to interact with laboratory scale

samples, and there are power sources available to generate microwaves at this

frequency.

Chapter-5

199

Microwave energy consists of an electric field and a magnetic field, though

only the electric field transfers energy to heat a substance. Magnetic field interactions

do not normally occur in chemical synthesis. Microwave move at the speed of light

(300,000 km/sec). The energy in microwave photons (0.037 kcal/mol) is very low

relative to the typical energy required to cleave molecular bonds (80-120 kcal/mol);

thus, microwaves will not affect the structure of an organic molecule. In the excitation

of molecules, the effect of microwave absorption is purely kinetic.

Traditionally, chemical synthesis has been achieved through conductive

heating with an external heat source. Heat is driven into the substance, passing first

through the walls of the vessel in order to reach the solvent and reactants. This is a

slow and inefficient method for transferring energy into the system because it depends

on the thermal conductivity of the various materials that must be penetrated. It results

in the temperature of the vessel being higher than that of the reaction mixture inside

until sufficient time has elapsed to allow the container and contents to attain thermal

equilibrium. This process can take hours. Conductive heating also hinders the

chemist’s control over the reaction. The heat source must physically be removed and

cooling administrated to reduce the internal bulk temperature.

Microwave heating on other hand, is a very different process. The microwaves

couple directly with the molecules those are present in the reaction mixture, leading to

a rapid rise in temperature. Because the process is not dependent upon the thermal

conductivity of the vessel materials, the result is an instantaneous localized

superheating of anything that will react to dipole rotation or ionic conduction, the

two fundamental mechanisms for transferring energy from microwaves to the

substance being heated. Microwave heating also offers facile reaction control. It can

be described as ‘instant on-instant off’. When the microwave energy is turned off,

latent heat is all that remains. Dipole rotation is an interaction in which polar

molecules try to align themselves with the rapidly changing electric field of the

microwave. The second way to transfer energy is ionic conduction, which results if

there are free ions or ionic species present in the substance being heated.

In a typical reaction coordinate, the process begins with reactants, which have

a certain energy level. In order to complete the transformation, these reactants must

collide in the correct geometrical orientation to become activated to a higher- level

transition state. The difference between these energy levels is the activation energy

required to reach this higher state. The activation energy is the energy that the system

Chapter-5

200

must absorb from its environment in order to react. Once enough energy is absorbed,

the reactants quickly react and return to a lower energy state-the products of the

reaction. Microwave irradiation does not affect the activation energy but provides the

momentum to overcome this barrier and complete the reaction more quickly than

conventional heating methods.

Since the first reports on the use of microwave heating to accelerate organic

chemical transformations by the groups of Gedye and Giguere/Majetich in 198618

,

more than 3500 articles have been published in the area of microwave-assisted

organic synthesis (MAOS). Since the late 1990s the number of publications related to

MAOS has increased dramatically to a point where it might be assumed that, in a few

years, most chemists will probably use microwave energy to heat chemical reactions

on a laboratory scale. In many instances, controlled microwave heating under sealed-

vessel conditions has been shown to dramatically reduce reaction times, increase

product yields, and enhance product purities by reducing unwanted side reactions

compared to conventional synthetic methods. The many advantages of this enabling

technology have not only been exploited for organic synthesis (MAOS) and in the

context of medicinal chemistry/drug discovery19

, but also penetrated fields such as

polymer synthesis20

, material sciences21

, nanotechnology22

, and biochemical

processes23

.

The microwave application under solvent less condition enables rapid

synthetic transformations at ambient pressure thus providing unique chemical

processes with special attributes such as ease of manipulation, enhanced reaction rates

and higher yields. The growing number of publications in microwave-assisted

synthesis includes virtually all types of chemical reactions such as additions,

cycloadditions, substitutions, eliminations, fragmentations etc.

5.2 Synthetic Aspect

One pot synthesis is the process through which one can less the amount of

environmental hazards, improve yields and save time. Some recent and important one

pot syntheses are summarized below:

M. P. Surpur et. al. carried out exploitation of the catalytic efficacy of Mg/Al

hydrotalcite for the reapid synthesis of 2-aminochromene derivatives via

multicomponent stratgy in presence of microwaves.24

Chapter-5

201

S. Tu and coworkers have reported the efficient one pot synthesis of

indeno[1,2-b]quinolines-9,11(6H,10H)dione from aldehyde, tetronic acid and

enaminones using microwave irradiation.25

O

O

CHO

Br

O

HN

+

N

OO

Br

AcOH

MW

The one pot synthesis of substituted 6-amino-5-cyanospiro-4-(piperidine-4’)-

2H,4H-dihydropyrazolo[3,4-b]pyrans has been reported by A. M. Shestopalov and

coworkers. 26

N

R1

O

N

N

O

H

R2

CN

CN

+ +

O

N

N

N

H

CN

NH 2

R1

R2Heat

Where: R1= Me, COCH3, COOEt

R2= Me, CH3OCH2, CH3CH2CH2

Using microwave heating in solid state, I. Devi and coworkers have reported

the one pot synthesis of novel pyrano[2,3-d]pyrimidines and pyrido[2,3-

d]pyrimidines.27

ArCHO CH2

CN

CN

OH

O

Ar

NH2

CNHT/MW

+ +140 0C

Chapter-5

202

N

N

R1

R2

O

O

OH

CHOPh

R3

CN

+ N

N O

R1

R2

O

O Ph

R3

NH2

MW

N

N

R1

R2

O

O

X

CHOPh

R3

CN

+ N

N N

R1

R2

O

O Ph

R3

NH2

MW

Where: R1=R2=H, CH3

R3=CN,COOEt

X= NH2, NHOH

The one pot, efficient and improved procedure for synthesis of pyran

annulated heterocyclic systems has been prepared by A. Shaabani and coworkers.28

Ph-CHOR

CN

O O

O

OH

CH3

O

O

O

R

NH2

Ph

O

OCH3

R

NH2

O PhHEAT

+H2O

Where: R=CN, COOEt

Chapter-5

203

J. Pospisil and M. Potacek have reported the microwave assisted solvent free

intramolecular 1,3-dipolar cycloaddition reactions leading to

hexahydrochromeno[4,3-b]pyrroles.29

CHO

O

+

R

HN COOEt

MW

O

N

COOEtR

Where: R= benzyl, ethyl, n-butyl, isopropyl, 1-adamantyl, tert-butyl

J. Zhou and coworkers have reported the facile one pot synthesis of

pyrano[2,3-c]pyrazole derivatives from aldehyde, malanonitrile and pyrazole under

microwave irradiation.30

N

N

Ph

H3C

O

CHOAr

CN

CN

+ Piperidine/ EtOH

MW

O

N

N

CN

NH2

Ar

Ph

H3C

One pot synthesis is also very useful tool for the synthesis of variety of

heterocycles which have significant pharmaceutical importance.

Ashraf H. F. Abd El-Wahab reported the novel chromene derivatives from

reaction of various cinnamonitrile compounds and 4-Hydroxycoumarin having

promising antibacterial activity.31

CN

CNH

Ar

O

OH

O

+O

O

ArO

CN

NH2

N. M. Evdokimov and coworkers reported the one pot synthesis of

heterocyclic privileged medicinal scaffolds like chromeno[2,3-b]pyridine using

structurally diverse aldehyde with various thiols and malononitrile. The libraries

Chapter-5

204

designed on the basis of such frameworks exhibit enhanced drug like properties and

results in high quality leads. The reported derivatives are similar to amlexanox

(antiallergic, antiulcer).32

CHO

OH

+

CN

CN

CN

CN

+ +

SH

R

O N

SR NH 2

CN

NH 2

Where: R=Ph, PhCH2, 2-NH2-Ph, 2-OH-Ph

W. Kemnitzer and coworkers have reported one pot synthesis, discovery and

development of the apoptosis-inducing 4-aryl-4H-chromenes as novel anticancer

agents which also possesses the vascular disrupting activity.33

+

HN OH

+

CN

CN

EtOH

Piperidine

HN O

CN

NH2

Ar

CHO

Ar

5.3 Present work

Present work describes the novel benzochromene derivatives bearing

substituted pyrazole moiety having the following general structure by one pot

synthesis using microwave irradiation.

O

NN

NH2

NH O

CN

Cl

CH3

R2

R1

R3

R1 = H, 4-CH3, 3-Cl

R2 = H, CH3, OCH3, OC2H5

R3 = Cl

Chapter-5

205

5.4 Experimental

This part of the chapter introduced totally eighteen new 3-Amino-1-(5-chloro-

3-methyl-1-(3 or 4-substitutedphenyl)-1H-pyrazol-4-yl)-2-cyano-N-(2 and 4-

substitutedphenyl)-1H-benzo[f]chromene-5-carboxamide derivatives (Bc1-18) having

the above general structure. The purity of all the synthesized compounds has been

checked by thin layer chromatography (TLC). TLC was runned using TLC aluminum

sheet silica gel 60 F254 (Merck) and chromatography was developed using a mixture of

toluene: ethylacetate (7:3).

The Microwave oven (700W) used was specially modified by RAGA’s

electromagnetic systems.

5.4A Synthesis of 3-Amino-1-(5-chloro-3-methyl-1-(3 or 4-substitutedphenyl)-

1H-pyrazol-4-yl)-2-cyano-N-(2 and 4-substitutedphenyl)-1H-benzo[f]chromene-

5-carboxamide (Bc1-18).

[3-chloro-5-methyl-1-(3or4-substituted-phenyl)pyrazol-4-yl]formaldehydes

(1.91gm, 0.01mol), malanonitrile (0.70 ml, 0.01mole), 3-hydroxy-N-(2 and 4-

substitutedphenyl)-2-naphthamide (2.63gm, 0.01mole) and ethanol (2-3 ml) were

charged in microwave flask and the contents in the flask were mixed thoroughly to

obtain a pest. To it piperidine (2-3 drops) is added. The flask was then heated under

microwave irradiation at power level 5 [350W (50%)] for 4 to 5 minutes. After the

completion of reaction (checked by TLC), the product was filtered and washed with

chilled ethanol. The product was crystallized with methanol.

5.4B Reaction Scheme

NNCl

CH3

CHO

CN

CN

OH

C=O

NH

O

NN

NH2

NH O

CN

Cl

CH3

Piperidine

EtOH

MW

R1

+ CH2 +

R2

R2

R1

R3

R3

4-5 min

Where: R1 = H, 4-CH3, 3-Cl

R2 = H, CH3, OCH3, OC2H5

R3 = Cl

Chapter-5

206

5.5 Results and Discussion

Reaction Scheme (5.5B) outlines the synthesis of final benzochromene

derivatives (Bc1-18).

Substituted anilines, naphthol derivatives and malanonitrile are commercial

products and were used without further purification. 5-chloro-1-(3 or 4 substituted

phenyl)-3-methyl-1H-pyrazol-4-carbaldehyde derivatives were synthesized as

described in Chapter 2, section 2.5A (i). All the solvents were distilled before use. All

the melting points are uncorrected and expressed in oC. Elemental analysis was

carried out by Perkin Elmer 2400 CHN analyzer. IR spectra of all the compounds

have been recorded on a Schimadzu FT-IR 8401 spectrophotometer using KBr disks.

The 1H-NMR and

13C-NMR spectra have been recorded on a Bruker AC 400F

(400MHz) instrument using TMS as internal standard in CDCl3 and DMSO-d6 as a

solvent.

The structures of the compounds were confirmed on the basis of elemental

analysis and spectral data. As an example, the IR spectra of compound Bc2 (R1= H,

R2= CH3, R3= H) shows band at 3484 cm-1

for N-H stretching, 3008 cm-1

for aromatic

C-H stretching, 2228 cm-1

for CN stretching, 1650 cm-1

for C=O stretching of -

NHCO, 1513&1422 cm-1

for C=C stretching of aromatic ring, 1215 cm-1

for C-O-C

stretching of Ar-O and 750 cm-1

for C-Cl stretching. 1H-NMR spectra of Bc2 showed

signal at δ 2.12, and δ 2.38 for two methyl group, two singlet at δ 4.88 and δ 5.27 for

amine group and methine group respectively and a multiplet due to the aromatic

protons around at δ 7.14-8.20. One singlet at δ 8.43 for -NH- of -NHCO group. The

13C-NMR spectrum of Bc2 was in good agreement with the structure assigned. The

peaks at δ 12.57 and δ 18.07 are assigned to two methyl carbons; peak at δ 28.74 is

attributed to methine carbon. The peak at 60.85 is assigned to carbon of carbonitrile

and the peaks at δ 114.12-159.25 are attributed to aromatic carbon.

Chapter-5

207

5.5A Characterization:

Table5.1: Physical properties of Compounds (Bc1-18)

Compd. R1 R2 R3 M.P.

(oC)

Mol.

Wt. Mol. Formula

Yield

%

Elemental Analysis

Calculated

(Found)

Bc1 H H H 225

532 C31H23ClN5O2 85 69.99

(69.91)

4.17

(4.22)

13.16

(13.12)

Bc2 H CH3 H 231

546 C32H24ClN5O2 83 70.39

(70.33)

4.43

(4.48)

12.83

(12.78)

Bc3 H OCH3 H 240

562 C32H24ClN5O3 82 68.39

(68.31)

4.30

(4.33)

12.46

(12.48)

Bc4 H OC2H5 H 295

576 C33H26ClN5O3 80 68.81

(68.83)

4.55

(4.50)

10.42

(10.26)

Bc5 H Cl H 260 566 C31H21Cl2N5O2 88 65.73

(65.78)

3.74

(3.78)

12.16

(12.12)

Bc6 H CH3 Cl 255

581 C32H23Cl2N5O2 82 66.21

(66.19)

3.99

(3.95)

12.06

(12.10)

Bc7 4-CH3 H H 227

546 C32H24ClN5O2 91 70.39

(70.35)

4.43

(4.39)

12.85

(12.89)

Bc8 4-CH3 CH3 H 252

560 C33H26ClN5O2 86 70.77

(70.72)

4.68

(4.64)

12.55

(12.58)

Bc9 4-CH3 OCH3 H 268

576 C33H26ClN5O3 90 68.81

(68.83)

4.55

(4.50)

12.16

(12.20)

Bc10 4-CH3 OC2H5 H 285

590 C34H28ClN5O3 89 69.21

(69.11)

4.78

(4.72)

11.57

(11.59)

Bc11 4-CH3 Cl H 250

581 C32H23Cl2N5O2 88 66.21

(66.19)

3.99

(3.95)

12.06

(12.10)

Bc12 4-CH3 CH3 Cl 275

595 C33H25Cl2N5O2 89 66.67

(66.64)

4.24

(4.20)

11.76

(11.72)

Bc13 3-Cl H H 259

566 C31H21Cl2N5O2 86 65.73

(65.80)

3.74

(3.70)

12.86

(12.82)

Bc14 3-Cl CH3 H 285

581 C32H23Cl2N5O2 90 66.21

(66.19)

3.99

(3.95)

12.06

(12.10)

Bc15 3-Cl OCH3 H 283

597 C32H23Cl2N5O3 90 64.44

(64.49)

3.89

(3.85)

11.74

(11.78)

Bc16 3-Cl OC2H5 H 291

610 C33H25Cl2N5O3 89 64.92

(64.97)

4.13

(4.16)

11.47

(11.42)

Bc17 3-Cl Cl H 286

601 C31H20Cl3N5O2 87 61.97

(61.92)

3.35

(3.40)

11.65

(11.70)

Bc18 3-Cl CH3 Cl 271

615 C32H22Cl3N5O2 89 62.50

(62.53)

3.61

(3.58)

11.59

(11.55)

Chapter-5

208

IR SPECTRA

1H-NMR SPECTRA

O

NN

NH2

NH O

CN

CH3

Cl

CH3

Chapter-5

209

Spectral data of compounds (Bc1-18)

3-Amino-1-(5-chloro-3-methyl-1-phenyl-1H-pyrazole-4-yl)-2-cyano-N-phenyl-

1H-benzo[f]chromene-5-carboxamide (Bc1).

IR

(KBR)

: 3484(N-H str.), 3008(aromatic C-H str.),

2228(-CN str.), 1650(C=O str. of-NHCO-),

1515&1420(C=C str. of aromatic ring),

1210(C-O-C str. of Ar-O), 753(C-Cl str.).

1H NMR

(CDCl3)

: 2.36 (s, 3H, CH3), 4.80(s, 2H, NH2) 5.24(s,

1H, CH), 7.12-8.21(m, 15H, Ar-H), 8.45(s,

1H, NH)

13C-NMR

(CDCl3)

: 12.50, 28.70, 60.75, 114.12, 118.17, 122.78,

123.11, 123.25, 124.88, 124.97, 125.55,

126.15, 127.17, 128.71, 128.98, 129.16,

129.73, 130.25, 131.46, 132.81, 135.25,

137.12, 138.33, 145.02, 147.37, 158.81,

159.25.

3-Amino-1-(5-chloro-3-methyl-1-phenyl-1H-pyrazole-4-yl)-2-cyano-N-o-toyl-1H-

benzo[f]chromene-5-carboxamide (Bc2).

IR

(KBR)


2220(-CN str.), 1675(C=O str. of -NHCO-),



1H NMR

(CDCl3)

: 2.12(s, 3H, CH3), 2.38(s, 3H, CH3), 4.88(s,

2H, NH2) 5.27(s, 1H, CH), 7.14-8.20(m, 14H,

Ar-H), 8.43(s, 1H, NH)

13C-NMR

(CDCl3)

: 12.57, 18.07, 28.74, 60.85, 114.12, 118.23,

122.36, 123.65, 123.85, 124.47, 124.78,

125.89, 126.98, 127.77, 128.74, 128.45,

128.52, 129.41, 129.24, 130.35, 130.50,

131.16, 132.93, 135.28, 137.71, 138.96,

145.58, 147.73, 158.19, 159.25.

O

NN

NH2

NH O

CN

CH3

Cl

CH3

O

NN

NH2

NH O

CN

Cl

CH3

Chapter-5

210

13C-NMR SPECTRA

O

NN

NH2

NH O

CN

CH3

Cl

CH3

Chapter-5

211

3-Amino-1-(5-chloro-3-methyl-1-phenyl-1H-pyrazole-4-yl)-2-cyano-N-(2-

methoxyphenyl)-1H-benzo[f]chromene-5-carboxamide (Bc3).

IR

(KBR)



1518&1425(C=C str. of aromatic ring), 1235

&1080(C-O-C asym & sym str. of -OCH3),

1217(C-O-C str. of Ar-O), 755 (C-Cl str.).

1H NMR

(CDCl3)

: δ 2.49(s, 3H, CH3), 3.82(s, 3H, OCH3), 4.68(s,

2H, NH2) 5.30(s, 1H, CH), 7.14-8.25(m, 14H,

Ar-H), 8.46(s, 1H, NH)

13C-NMR

(CDCl3)

: δ 12.18, 28.84, 56.03, 60.83., 114.09, 118.93,

122.99, 123.01, 123.20, 124.88, 124.92,

125.65, 126.34, 127.05, 128.16, 128.76,

128.96, 129.26, 129.84, 130.27, 130.69,

131.66, 132.14, 135.65, 137.45, 138.01,

145.13, 147.72, 158.29, 159.10.


ethoxyphenyl)-1H-benzo[f]chromene-5-carboxamide (Bc4).

IR

(KBR)




1212(C-O-C str. of Ar-O), 758(C-Cl str).

1H NMR

(CDCl3)

: δ 1.35(s, 3H, CH3), 2.39(s, 3H, CH3), 4.18(s,

3H, OCH2), 5.40(s, 1H, CH), 7.08(s, 2H,

NH2) 7.26-8.40(m, 14H, Ar-H), 9.46(s, 1H,

NH).

13C-NMR

(CDCl3)

: δ 12.18, 15.23, 28.85, 55.63, 60.89, 114.17,

118.23, 122.32, 123.21, 123.14, 124.45,

124.56, 125.89, 126.78, 127.96, 128.67,

128.91, 128.37, 129.28, 129.39, 130.19,

130.29, 131.25, 132.26, 135.49, 137.88,

138.39, 145.73, 147.34, 158.14, 159.98.

O

NN

NH2

NH O

CN

Cl

CH3

OMe

O

NN

NH2

NH O

CN

Cl

CH3

OC2H

5

Chapter-5

212


chlorophenyl)-1H-benzo[f]chromene-5-carboxamide (Bc5).

IR

(KBR)





1H NMR

(CDCl3)

: δ 2.32(s, 3H, CH3), 5.41(s, 1H, CH), 4.56(s,

2H, NH2) 5.33(s, 1H, CH), 7.19-8.29(m, 14H,

Ar-H), 8.49(s, 1H, NH).

13C-NMR

(CDCl3)

: δ 12.56, 28.54, 60.89, 114.41, 118.74, 122.84,

123.25, 123.96, 124.85, 124.78, 125.65,

126.12, 127.32, 128.54, 128.89, 128.79,

129.64, 129.97, 130.31, 130.34, 131.67,

132.91, 135.38, 137.74, 138.39, 145.73,

147.23, 158.71, 159.65.

3-Amino-1-(5-chloro-3-methyl-1-phenyl-1H-pyrazole-4-yl)-2-cyano-N-(4-chloro

2-methylphenyl)-1H-benzo[f]chromene-5-carboxamide (Bc6).

IR

(KBR)





1H NMR

(CDCl3)

: δ 2.14 (s, 3H, CH3), 2.39(s, 3H, CH3), 4.90(s,

2H, NH2) 5.32(s, 1H, CH), 7.17 -8.25(m, 13H,

Ar-H), 8.51(s, 1H, NH).

13C-NMR

(CDCl3)

: δ 12.90, 18.25, 28.84, 60.32, 114.45, 118.13,

122.97, 123.78, 123.65, 124.21, 124.73,

125.91, 126.32, 127.21, 128.45, 128.55,

128.69, 129.65, 129.98, 130.05, 130.71,

131.47, 132.15, 135.65, 137.35, 138.51,

145.43, 147.61, 158.78, 159.91.

O

NN

NH2

NH O

CN

Cl

CH3

Cl

O

NN

NH2

NH O

CN

Cl

CH3

CH3

Cl

Chapter-5

213

3-Amino-1-(5-chloro-3-methyl-1-p-tolyl-1H-pyrazole-4-yl)-2-cyano-N-phenyl-1H-


IR

(KBR)





1H NMR

(DMSO-d6)

: δ 2.09(s, 3H, CH3), 2.32(s, 3H, CH3), 4.88(s,

2H, NH2) 5.26(s, 1H, CH), 7.17 -8.29 (m, 14H,

Ar-H), 8.55(s, 1H, NH)

13C-NMR

(DMSO-d6)

: δ 12.78, 21.32, 28.14, 60.69, 114.87, 118.74,

122.56, 123.32, 123.71, 124.12, 124.97,

125.36, 126.87, 127.65, 128.74, 128.56,

129.47, 129.98, 130.22, 131.09, 132.41,

135.17, 137.94, 138.43, 145.31, 147.91,

158.00, 159.85.

3-Amino-1-(5-chloro-3-methyl-1-p-tolyl-1H-pyrazole-4-yl)-2-cyano-N-o-toyl-1H-


IR

(KBR)



1518 & 1424(C=C str. of aromatic ring), 1219

(C-O-C str. of Ar-O), 753(C-Cl str.).

1H NMR

(DMSO-d6)

: δ 2.07(s, 3H, CH3), 2.15(s, 3H, CH3), 2.35(s,

3H, CH3), 4.85(s, 2H, NH2) 5.25(s, 1H, CH),

7.15-8.25 (m, 13H, Ar-H), 8.45(s, 1H, NH)

13C-NMR

(DMSO-d6)

: 12.12, 18.98, 21.35, 28.23, 60.87, 114.36,

118.74, 122.65, 123.55, 123.41, 124.25,

124.63, 125.96, 126.58, 127.74, 128.14,

128.74, 128.85, 129.25, 129.37, 130.91,

130.46, 131.31, 132.29, 135.71, 137.39,

138.73, 145.94, 147.67, 158.03, 159.99.

O

NN

NH2

NH O

CN

Cl

CH3

CH3

O

NN

NH2

NH O

CN

Cl

CH3

CH3

CH3

Chapter-5

214

IR SPECTRA

1H-NMR SPECTRA

O

NN

NH2

NH O

CN

Cl

CH3

CH3

OC2H

5

Chapter-5

215

3-Amino-1-(5-chloro-3-methyl-1- p-tolyl -1H-pyrazole-4-yl)-2-cyano-N-(2-

methoxyphenyl)-1H-benzo[f]chromene-5-carboxamide (Bc9).

IR

(KBR)




&1025(C-O-C asym & sym str. of-OCH3),

1210(C-O-C str. of Ar-O), 741(C-Cl).

1H NMR

(DMSO-d6)

: δ 2.11(s, 3H, CH3), 2.38(s, 3H, CH3), 3.76(s,

3H, OCH3), 4.56(s, 2H, NH2) 5.56(s, 1H,

CH), 7.18-8.29(m, 14H, Ar-H), 8.58(s, 1H,

NH)

13C-NMR

(DMSO-d6)

: δ 12.17, 21.30, 28.78, 56.33, 60.91, 114.17,

118.93, 122.99, 123.01, 123.20, 124.88,

124.92, 125.45, 126.23, 127.63, 128.56,

128.45, 128.56, 129.23, 129.45, 130.07,

130.41, 131.12, 132.98, 135.77, 137.87,

138.77, 145.12, 148.0 2, 159.33, 162.33.

3-Amino-1-(5-chloro-3-methyl-1-p-tolyl-1H-pyrazole-4-yl)-2-cyano-N-(2-

ethoxyphenyl)-1H-benzo[f]chromene-5-carboxamide (Bc10).

IR

(KBR)


2232(-CN str.), 1660(C=O str. of -NHCO-),


1217(C-O-C str. of Ar-O), 755(C-Cl ).

1H NMR

(DMSO-d6)

: δ 1.38(s, 3H, CH3), 2.09(s, 3H, CH3), 2.35(s,

3H, CH3), 4.12(s, 3H, OCH2), 5.44(s, 1H, CH),

7.09(s, 2H, NH2) 7.31 -8.44(m, 14H, Ar-H),

9.54(s, 1H, NH).

13C-NMR

(DMSO-d6)

: δ 12.63, 15.08, 28.93, 55.73, 64.53, 112.47,

114.19, 119.99, 120.19, 120.32, 120.66,

122.06, 123.06, 124.33, 124.93, 125.19,

126.29, 127.95, 129.41, 130.07, 131.39,

131.76, 135.63, 138.30, 144.31, 147.49,

149.51, 159.47, 159.59, 162.80, 177.75

O

NN

NH2

NH O

CN

Cl

CH3

CH3

OMe

O

NN

NH2

NH O

CN

Cl

CH3

CH3

OC2H

5

Chapter-5

216

13C-NMR SPECTRA

O

NN

NH2

NH O

CN

Cl

CH3

CH3

OC2H

5

Chapter-5

217

3-Amino-1-(5-chloro-3-methyl-1-p-tolyl-1H-pyrazole-4-yl)-2-cyano-N-(2-

chlorophenyl)-1H-benzo[f]chromene-5-carboxamide (Bc11).

IR

(KBR)





1H NMR

(DMSO-d6)

: δ 2.13(s, 3H, CH3), 2.35(s, 3H, CH3), 5.49(s,

1H, CH), 4.68(s, 2H, NH2) 5.89(s, 1H, CH),

7.22 -8.32 (m, 14H, Ar-H), 8.79(s, 1H, NH).

13C-NMR

(DMSO-d6)

: δ 12.85, 21.55, 28.69, 60.45, 114.45, 118.09,

122.12, 123.14, 123.56, 124.44, 124.71,

125.09, 126.09, 127.07, 128.66, 128.45,

128.12, 129.85, 130.97, 130.99, 131.34,

131.88, 132.01, 135.49, 137.93, 139.87,

148.45, 150.33, 158.12, 160.58.

3-Amino-1-(5-chloro-3-methyl-1-phenyl-1H-pyrazole-4-yl)-2-cyano-N-(4-chloro

2-methylphenyl)-1H-benzo[f]chromene-5-carboxamide (Bc12).

IR

(KBR)

: 3475 (N-H str.), 3020(aromatic C-H str.),




1H NMR

(DMSO-d6)

: δ 2.07(s, 3H, CH3), 2.18(s, 3H, CH3), 2.37(s,

3H, CH3), 4.86 (s, 2H, NH2) 5.45(s, 1H, CH),

7.23 -8.25(m, 13H, Ar-H), 8.88(s, 1H, NH).

13C-NMR

(DMSO-d6)

: δ 12.45, 18.12, 21.32, 28.48, 60.16, 114.23,

118.07, 122.47, 123.36, 123.33, 124.11,

124.35, 125.46, 126.45, 127.11, 128.23,

128.27, 128.33, 129.34, 129.48, 130.22,

130.35, 131.28, 132.07, 135.34, 137.18,

138.25, 145.23, 149.30, 160.37, 162.46.

O

NN

NH2

NH O

CN

Cl

CH3

CH3

Cl

O

NN

NH2

NH O

CN

Cl

CH3

CH3

CH3

Cl

Chapter-5

218

3-Amino-1-(5-chloro-3-methyl-1-(3-chlorophenyl)-1H-pyrazole-4-yl)-2-cyano-N-

phenyl-1H-benzo[f]chromene-5-carboxamide (Bc13).

IR

(KBR)





1H NMR

(DMSO-d6)

: δ 2.37(s, 3H, CH3), 4.91(s, 2H, NH2) 5.30(s,

1H, CH), 7.17-8.25(m, 15H, Ar-H), 8.45(s,

1H, NH)

13C-NMR

(DMSO-d6)

: δ 12.10, 28.32, 60.56, 114.36, 118.51, 122.39,

123.33, 123.79, 124.42, 124.49, 126.00,

126.45, 127.53, 128.38, 128.49, 129.50,

129.99, 130.78, 131.20, 132.43, 135.78,

137.12, 138.33, 145.02, 147.37, 158.81,

159.89, 162.78, 171.95.

3-Amino-1-(5-chloro-3-methyl-1- (3-chlorophenyl)-1H-pyrazole-4-yl)-2-cyano-N-

o-toyl-1H-benzo[f]chromene-5-carboxamide (Bc14).

IR

(KBR)





1H NMR

(DMSO-d6)

: δ 2.14(s, 3H, CH3), 2.36(s, 3H, CH3), 4.87 (s,

2H, NH2) 5.32(s, 1H, CH), 7.28 -8.28(m, 14H,

Ar-H), 8.5(s, 1H, NH)

13C-NMR

(DMSO-d6)

: δ 12.08, 18.21, 28.36, 60.43, 114.36, 118.50,

120.36, 122.75, 123.35, 123.49, 124.98,

124.39, 125.42, 126.49, 127.40, 128.47,

128.00, 128.93, 129.84, 129.65, 130.90,

130.99, 131.51, 132.03, 135.59, 137.39,

138.44, 145.56, 147.47, 158.59, 159.78,

165.87.

O

NN

NH2

NH O

CN

Cl

CH3

Cl

O

NN

NH2

NH O

CN

Cl

CH3

Cl

CH3

Chapter-5

219


(2-methoxyphenyl)-1H-benzo[f]chromene-5-carboxamide (Bc15).

IR

(KBR)




1220(C-O-C str. of Ar-O), 758(C-Cl).

1H NMR

(DMSO-d6)

: δ 2.40(s, 3H, CH3), 3.86 (s, 3H, OCH3), 4.60

(s, 2H, NH2) 5.35(s, 1H, CH), 7.14-8.25(m,

14H, Ar-H), 8.60(s, 1H, NH).

13C-NMR

(DMSO-d6)

: δ 12.36, 28.48, 56.15, 60.88., 114.27, 118.48,

122.47, 123.15, 123.42, 124.46, 124.48,

125.36, 126.65, 127.12, 128.39, 128.40,

128.45, 129.55, 129.40, 130.58, 130.95,

131.25, 132.33, 135.39, 137.98, 138.18,

140.47, 145.26, 147.38, 158.55, 159.22,

168.23.


(2-ethoxyphenyl)-1H-benzo[f]chromene-5-carboxamide (Bc16).

IR

(KBR)




(C-O-C str. of Ar-O), 750(C-Cl)

1H NMR

(DMSO-d6)

: δ 1.29(s, 3H, CH3), 2.31 (s, 3H, CH3), 4.22(s,

3H, OCH2), 5.45(s, 1H, CH), 7.13(s, 2H,

NH2) 7.24-8.42(m, 14H, Ar-H), 9.41(s, 1H,

NH).

13C-NMR

(DMSO-d6)

: δ 12.20, 15.25, 28.87, 55.65, 60.91, 114.34,

118.54, 122.66, 123.43, 123.30, 124.92,

124.63, 125.40, 126.39, 127.49, 128.39,

128.43, 128.36, 129.56, 129.80, 130.36,

130.36, 131.55, 132.54, 135.98, 137.42,

138.80, 145.09, 147.69, 158.56, 159.63,

164.32, 171.23.

O

NN

NH2

NH O

CN

Cl

CH3

Cl

OMe

O

NN

NH2

NH O

CN

Cl

CH3

Cl

OC2H

5

Chapter-5

220


(2-chlorophenyl)-1H-benzo[f]chromene-5-carboxamide (Bc17).

IR

(KBR)


2220(-CN str.), 1665 (C=O str. of-NHCO-),


1212(C-O-C str. of Ar-O), 755 (C-Cl str.).

1H NMR

(DMSO-d6)

: δ 2.30 (s, 3H, CH3), 5.44(s, 1H, CH), 4.58 (s,

2H, NH2) 5.69(s, 1H, CH), 7.23 -8.33(m, 14H,

Ar-H), 8.58(s, 1H, NH).

13C-NMR

(DMSO-d6)

: δ 12.19, 28.55, 60.93, 114.80, 118.39, 122.47,

123.01, 123.18, 123.48, 124.43, 124.38,

125.00, 126.12, 127.60, 128.98, 128.43,

128.39, 129.31, 129.39, 130.60, 130.75,

131.45, 132.44, 135.90, 137.71, 138.15,

145.25, 147.50, 158.91, 159.45, 165.81.


(4-chloro 2-methylphenyl)-1H-benzo[f]chromene-5-carboxamide (Bc18).

IR

(KBR)

: 3475 (N-H str. of), 3005(aromatic C-H str.),




1H NMR

(DMSO-d6)

: δ 2.11 (s, 3H, CH3), 2.36 (s, 3H, CH3), 4.95

(s, 2H, NH2) 5.36 (s, 1H, CH), 7.17 -8.29(m,

13H, Ar-H), 8.89(s, 1H, NH).

13C-NMR

(DMSO-d6)

: δ 12.18, 18.23, 28.91, 60.62, 114.91, 118.58,

122.45, 123.52, 123.38, 124.45, 124.35,

125.42, 126.66, 127.48, 128.90, 128.99,

128.35, 129.39, 129.48, 130.25, 130.41,

131.19, 132.30, 135.35, 136.90 137.72,

138.99, 145.87, 147.72, 158.48, 159.78

169.23.

O

NN

NH2

NH O

CN

Cl

CH3

Cl

Cl

O

NN

NH2

NH O

CN

Cl

CH3

Cl

CH3

Cl

Chapter-5

221

5.5B Antimicrobial activity

The methods used for antibacterial and antifungal activity are discussed in Chapter-2,

2.5B.

Table 5.2: Antimicrobial activity of compounds Bc1-12

Inhibition zone (in mm)

Compd.

E.coli B.substilis S.aureus F.oxysporum A.niger R.oryzae

Bc1 19 24 19 15 18 25

Bc2 16 17 24 14 24 20

Bc3 20 24 20 20 19 17

Bc4 24 18 18 15 23 17

Bc5 22 20 20 15 16 25

Bc6 20 25 23 16 18 22

Bc7 17 23 16 13 24 20

Bc8 17 19 25 15 18 25

Bc9 22 19 18 21 24 20

Bc10 18 24 17 20 20 19

Bc11 25 20 20 17 19 25

Bc12 20 19 24 13 18 20

Bc13 25 18 19 14 19 24

Bc14 20 23 20 12 20 18

Bc15 19 17 25 15 25 18

Bc16 24 20 20 20 24 19

Bc17 20 25 17 12 20 23

Bc18 25 19 24 14 17 20

Ampicillin 28 30 30 --- --- ---

Ciprofloxacin 35 34 33 --- --- ---

Griseofulvin --- --- --- 26 28 30

Chapter-5

222

Results of antimicrobial activity

All the synthesized benzochromene derivatives were tested against

microorganism species at 1000 ppm concentration.

The data enumerated in the Table 5.2 reveal that the compounds Bc4, Bc5,

Bc9, Bc11, Bc13, Bc16 and Bc18 show good activity against gram negative bacteria

E.coli, compounds Bc1, Bc3 Bc6, Bc7, Bc10, Bc14 and Bc17 and compounds Bc2, Bc6

Bc8, Bc12, Bc15 and Bc18 show good activity against gram positive bacteria B.substilis

and S.aureus respectively compared to the standard drug Ampicillin. And all other

synthesized compounds are moderately active against the tested gram positive and

gram negative bacteria compared to the standard drug Ampicillin and Ciprofloxacin.

From the antifungal assay it has been observed that compounds Bc3, Bc9, Bc10,

and Bc16 show good activity against F.oxysporum, compounds Bc2, Bc4 Bc7, Bc9, Bc15

and Bc16 show good activity against A.niger and compounds Bc1, Bc5, Bc67, Bc8, Bc11,

Bc13 and Bc17 show good activity agains R.oryzae compared to the standard drug

Griseofulvin. Rest of the compounds show significant activity compared to the

standard drug Griseofulvin.

Chapter-5

223

Figure 5.1: Antibacterial Chart

An

tib

ac

teri

al c

ha

rt

0510

15

20

25

30

35

40

Bc1B

c2B

c3B

c4B

c5B

c6B

c7B

c8B

c9B

c10 B

c11 B

c12 B

c13 B

c14 B

c15 B

c16 B

c17 B

c18

Am

pici

llin

Cip

roflo

xaci

n

Co

mp

ou

nd

s

Inhibition zone (in mm)

E.c

oli

B.s

ubstilis

S.a

ure

us

Chapter-5

224

Figure 5.2: Antifungal Chart

An

tifu

ng

al c

ha

rt

05

10

15

20

25

30

35

Bc1B

c2B

c3B

c4B

c5B

c6B

c7B

c8B

c9B

c10 B

c11 B

c12 B

c13 B

c14 B

c15 B

c16 B

c17 B

c18

Gris

eofu

lvin

Co

mp

ou

nd

s

Inhibition zone (In mm)

F.o

xysporu

m

A.n

iger

R.o

ryzae

Chapter-5

225

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