Synthesis, Characterization and Antifungal Activity of Novel … · 2019. 7. 31. · Synthesis, Characterization and Antifungal Activity S447 Synthesis of ligands HL 1 and HL 2 For

ISSN: 0973-4945; CODEN ECJHAO

E-Journal of Chemistry

http://www.e-journals.net 2009, 6(S1), S445-S451

Synthesis, Characterization and Antifungal

Activity of Novel Quinazolin-4-one

Derivatives Containing 8-Hydroxyquinazoline

Ligand and its Various Metal Complexes

R. T. VASHI* and S. B. PATEL

Department of Chemistry,

Navyug Science College, Rander Road, Surat-395009, India.

[email protected]

Received 24 February 2009; Accepted 20 April 2009

Abstract: Novel ligands containing quinazoline-4-one-8-hydroxyquinoline (QQ)

merged moieties were prepared and characterized. For this anthranilic acid and 5-

bromoanthranilic acid were converted respectively into 2-chloromethyl–3-(4-methyl

phenyl)-3(H)-quinazoline-4-one and 2-chloromethyl–3-(methyl phenyl)-6-bromo-

3(H)-quinazoline-4-one. Both these compounds were condensed with 5-amino-8-

hydroxyquinoline. The so called resulted compounds were named respectively as 2-

[(8-hydroxy-quinolinyl) –5- amino methyl] -3-(4-methylphenyl)- 3(H)- quinazoline -

4- one and 2-[(8-hydroxyquinolinyl)-5-aminomethyl] -3(methyl phenyl)-6-bromo-

3(H)-quinazoline-4-one. Both the compounds were designated respectively as HL1

and HL2 ligands. The transition metal (Cu2+, Ni2+, Zn2+, Mn2+ and Co2+) complexes

of both these ligands were prepared. The ligands and their complexes as case may be

were characterized by elemental analysis, spectral studies and number of hydroxyl

groups. The stoichiometry of the complexes has been found to be 1:2 (metal: ligand).

An octahedral geometry around Co2+, Ni2+ and Mn2+, distorted octahedral geometry

around Cu2+ and tetrahedral geometry of around Zn2+ have been proposed. These

complexes also been tested for their antifungal activities.

Keywords: Ligands, 8-hydroxyquinoline, IR spectral studies, Magnetic moment and Antifungal study.

Introduction

The heterocyclic nitrogen compounds especially quinazolinone derivatives play a vital role in

many biological processes and as synthetic drugs1-3

. Quinazolin-4-one is also well known for

many pharmaceutical products4-6

. Ligand 8-hydroxyquinoline is not only act as a complexing

agent but also applied for drug synthesis7. The formation of 8-hydroxyquinoline and quinazolin-

4-one molecules into one molecule has not received any attention in spite of well-defined

S446 R. T. VASHI et al.

applications of both the molecules. Hence the initial work in this direction has been carried

out8. Thus in the extension of this work

8, present communication comprises the synthesis,

characterization and chelating properties of novel qunazolin-4-one-8-hydroxyquinoline

derivatives. The whole work is summarized in Scheme 1.

R1

NH2

COOH R1

NHCOCH2Cl

COOH

R1

N

N

O

CH2Cl

N

N

N

O

R1

CH

2

NH

OH

N

N

N

O

R1

C

H2

NH

O

N

N

N

O

R1

CH

2

NH

O

Mt

Anthranilic acid

ClCH2COCl

2-Chloromethyl-3-(H)-aryl-quinazolin-4-one

N-Chloroacetyl anthranic acid

POCl3

5-amino-8-hydroxy quinoline

Aromatic amine

+

QQ LigandMetal salt

YY

QQ-Metal complex

Where, R1 = H, Br

Y = H2O or Acetate

Mt = Cu2+

, Mn2+

, Co2+

, Ni2+

, Zn2+

Scheme 1.

Experimental

All the chemicals used were of pure grade (Merck and B.D.H). The melting points of both

ligands HL1 and HL2 were determined by DSC method and were uncorrected.

Synthesis, Characterization and Antifungal Activity S447

Synthesis of ligands HL1 and HL2

For the preparation of ligand HL1, a mixture of 2-chloromethyl–3-(4-methylphenyl)-3(H)-

quinazoline-4-one (0.01 mole) and 5-amino-8-hydroxyquinoline (0.01 mole) and for the

preparion of ligand HL2, a mixture of 2-chloromethyl–3-(methylphenyl)-6-bromo-3(H)-

quinazoline-4-one (0.01 mole) and 5-amino-8-hydroxyquinoline (0.01 mole) were taken

in dry pyridine (20 mL) and was refluxed for 12 h. Pyridine was distilled off as much as

possible and the residue was poured into a little crushed ice with stirring. The products

were separated out, filtered, washed with water and finally with ethanol. The air dried

products were used. Melting point of HL1 was ~209 °C and for HL2 was ~232.2 °C

(Uncorrected).

Synthesis of complexes

A dried ligand sample HL1 or HL2 (0.01 M) was stirred in 85 % (v/v) formic acid and then it

was diluted by water until complete dissolution. The resultant solution was designated as

reagent solution. This solution was used for preparation of complexes with transition metal

ions. The formic acid solution of ligand was added drop wise to a solution of cupric nitrate

hexahydrate, nickel nitrate hexahydrate, cobalt nitrate hexahydrate, manganese chloride

hexahyrade, zinc nitrate hexahydrate (0.005 mole) in 100 mL of water respectively with rapid

stirring. The resultant pH 4.5 (for Cu+2

), pH 6.0 (for Ni+2

and Co+2

) and pH 5.6 (Mn+2

and Zn+2

)

was maintained by adding of sodium acetate. A dark coloured solid was precipitated out. It

was allowed to settle and digested on water bath at 70 °C for about 2 h. The solid mass was

filtered, washed with 1:1 mixture of water-ethanol and finally with acetone and dried. The

percentage yield of complexes was in the range of 65-82%. All the complexes were powdered

well and dried at 70 °C over a period of 24 h.

Measurements

The C, H and N contents of metal complexes were determined on elemental analyzer

Thermofiniggan 1101 Flash EA (ITALY). The metal contents were estimated using standard

methods9.

1H NMR spectra of ligands were recorded on Bruker NMR spectrophotometer

using TMS as an internal standard in CDCl3/DMSO-d610

. The molar conductance of the

complexes in DMF (10-3

M) solutions were measured at room temperature using Systronics

model 305 direct reading conductivity bridge. The infrared spectra (KBr) were recorded in the

range 4000-600 cm-1

with a Nicolet-760 spectrophotometer. Reflectance spectra of complexes

were recorded on a Beckman–DK-2A spectrophotometer using MgO as reference. Magnetic

susceptibility was measured by Gouy’s method11

at room temperature (300 K) using

Hg[Co(CNS)4] as calibrant12

, and the effective magnetic moment were calculated from

relation13

, µeff = 2.84√Xm x T, where T is the absolute temperature. Diamagnetic corrections

were made by using Pascal’s constants.

The ligands and their metal complexes were screen at 1000 ppm concentration in vitro for

their antifungal activity against five fungi viz. Erysiphe pisi, Nigrospora sp., Trichoderma sp.,

Aspergillus niger, Curvularia lunata. The antifungal activity of the compounds was measured

by plate method. Five days old cultures were suspended in potato dextrose agar (PDA)

medium and autoclaved at 1200 °C for 15 minutes at 15 atmospheric pressure. The percentage

inhibition of fungi was calculated after 5 days using the formula given below,

Percentage of Inhibition = 100 (X-Y) / X

Where X = area of colony in control plate (without sample)

and Y = area of colony in test plate.


Results and Discussion

The synthesis of ligands HL1 and HL2 was performed by method reported for 2-chloromethyl–

3-(4-methylphenyl)-3(H)-quinazoline-4-one. The C, H and N of both ligands are consistent

with predicted structure.

NMR spectra

The 1H NMR spectra of both ligands gave the multiplate between 6.88-7.8 δ ppm for aromatic

protons, signal at 5.74-5.98 δ ppm for singlet of phenolic –OH group, 3.35-3.77 δ ppm due to CH2

bridge, 1.23 d ppm for –CH3 group and 11.1-11.35 δ ppm due to –NH group. The non-aqueous

conductometric titration at both ligands gave the proton of –CH2 and –OH group in ligands.

The complexes are microcrystalline coloured powders having melting points higher than the

ligands. They are stable in air at room temperature. All compounds gave satisfactory elemental

analysis, suggesting 1:2 (metal:ligand) stoichiometry. Elemental and molar conductance data are

shown in Table 1. The result indicates that they are less polar in DMF. Very low molar

conductance values in the range of 5.11 to 21.72 ohm-1

cm2

mol-1 in Mn

2+, Ni

2+, Cu

2+ and Zn

2+

complexes indicates that they are non-electrolytic14

and monomeric in nature (ML2 type

complexes). The low ΛM values may be attributed to the large cations15

. The electrical conductivity

of these complexes found in the decreasing order as follows: Co > Ni > Zn > Mn > Cu.

Infrared spectra

IR spectrum of ligands HL1 and HL2 show a broad band extended from 3700 to 2600 cm-1

which might be responsible to phenolic -OH group bonded to N atom of 8-hydroxyquinoline

moieties16-17

. The inflextious at 2920, 2850 and 1470 cm-1

are due to aromatic -CH2 and

methylene group of bridge18-19

. The strong band at 1700 cm-1

is attributed to -C=O of

quinazoline 4-one moiety. Band at 3400 cm-1

for –NH group. Several bands appeared between

1500-1600 cm-1

region may arised from aromatic breathing. The IR band at 1580 cm-1

(C=N

of 8-quinolinol system) of HL1 and HL2 ligands shifted to higher frequency side ~1600 cm-1

in the spectra of the metal complexes indicating involvement of nitrogen in the complexes

formation16,20

. Most of bands appeared in the spectra of corresponding ligand are observed at

their metal complexes. Only a new band at 1095 cm-1

had appeared in the spectra of metal

complexes. This may be assigned to υc-o of C-O-M bond formation. All the complexes show

additional bands at 840-830 cm-1

indicating the presence of coordinated water21

.

Magnetic moment and electronic spectra

At the room temperature, µeff values for the Co+2

complexes (3.99-4.51 B.M.) suggest high spin

octahedral geometry, which is further supported by the electronic spectral data. The electronic

spectrum of the Co2+

complexes shows three bands at 8960, 18650-18980 and 22590-23710 cm-1,

assignable to 4T1g (F)

4T1g (F) (υ1),

4T1g (F)

4A2g (F) (υ2) and

4T1g (F)

4T1g (P) (υ3)

transitions, respectively for an octahedral geometry22

. The values of transition ratio υ2 / υ1 is 2.08

providing further evidences for octahedral geometry for the Co2+

complexes.

In the Ni+2

complexes, µeff values at room temperature are in the range 2.97-3.12 B.M.

as expected for six coordinated spin free Ni+2

species23

. The reflectance spectra of the Ni2+

complexes, exhibit two strong bands at 15620-15625 cm-1

and 22470-22478 cm-1

,

assignable to 3A2g (F)

3T1g (F) (υ1) and

3A2g (F)

3T1g (P) (υ2) respectively. The

spectral bands are well within the range observed for hexacoordinate octahedral complexes

reported earlier24

. The Cu+2

complexes exhibit normal magnetic moments (1.70-1.81 B.M.)

corresponding to one unpaired electron indicating the distorted octahedral geometry,

which is in agreement with data reported by several research workers25-26

.

Sy

nth

esis, Ch

aracterization

and

An

tifung

al Activ

ity S

44

9

Table 1. Analytical and physical data of ligand and complexes.

Mol Formula M.W.

g/mol

Yield

%

Elemental Analysis, %

Found (Calcd.)

ΛM

ohm-1

cm2mol

-1

Ligand /

Complexes C H N Br M

µeff

B.M.

HL 1 C25H20N4O2 408 72 73.50

(73.52)

4.80

(4.90)

13.70

(13.72) - - - -

HL 2 C25H19N4O2Br 487 75 61.50

(61.61)

3.80

(3.90)

11.40

(11.49)

16.30

(16.42) - - -

(HL1) Cu+2

C50H38N8O4 Cu+2

.2H2O 913.54 72 65.60

(65.68)

4.10

(4.60)

12.20

(12.26) -

6.90

(6.96) 1.81 8.10

(HL2) Cu+2

C50H38N8O4.Br2 Cu+2

.2H2O 1073.54 77 54.20

(54.42)

3.50

(3.63)

10.00

(10.16)

14.70

(14.93)

5.60

(5.76) 1.70 5.11

(HL1) Ni+2

C50H38N8O4 Ni+2

.2H2O 908.69 69 66.00

(66.03)

4.10

(4.62)

12.30

(12.33) -

6.40

(6.46) 2.97 9.31

(HL2) Ni+2

C50H38N8O4 .Br2. Ni+2

2H2O 1068.69 79 54.50

(54.66)

3.40

(3.64)

9.80

(10.20)

14.80

(14.99)

5.20

(5.35) 3.12 17.20

(HL1) Mn+2

C50H38N8O4 Mn+2

.2H2O 904.93 79 66.00

(66.30)

4.10

(4.64)

12.30

(12.38) -

6.00

(6.07) 5.13 6.10

(HL2) Mn+2

C50H38N8O4 .Br2 Mn+2

H2O 1064.93 82 54.70

(54.85)

3.40

(3.66)

10.00

(10.24)

14.90

(15.05)

4.90

(5.02) 5.11 7.12

(HL1) Co+2

C50H38N8O4 Co+2

.2H2O 908.93 76 66.00

(66.01)

4.10

(4.62)

12.30

(12.32) -

6.40

(6.48) 3.99 21.72

(HL2) Co+2

C50H38N8O4 .Br2.Co+2.

2H2O 1068.93 66 54.50

(54.65)

3.50

(3.64)

9.90

(10.20)

14.80

(14.99)

5.20

(5.37) 4.51 18.10

(HL1) Zn+2

C50H38N8O4 Zn+2

.2H2O 915.39 70 65.50

(65.55)

4.10

(4.59)

12.20

(12.24) -

7.10

(7.14) - 9.80

(HL2) Zn+2

C50H38N8O4.Br2. Zn+2

.2H2O 1075.39 65 54.20

(54.33)

3.40

(3.62)

10.00

(10.14)

14.70

(14.90)

5..08

(5.92) - 8.22


Electronic spectra of these complexes show broad asymmetric bands in the region 14980–

15490 cm-1

and at 23690-24650 cm-1

assignable 2B1g

2A1g and charge transfer transition

respectively27

. These results reveal the distorted octahedral geometry for these complexes.

The former band may be due to 2Eg

2T2g accounted due to Jahn Teller effect suggesting

thereby a distorted octahedral geometry for these complexes28

. Zn+2

complexes are

diamagnetic in nature and their electronic spectra do not furnish any characteristic d-d

transitions except charge transfer (C.T.) bands as expected for d10

systems and may have

tetrahedral geometry29

. There is no evidence for the characteristic bands of coordinated water

in IR spectra.

The electronic spectra of the Mn2+

complexes exhibited three spin allowed bands in the

region 14589-15896 cm-1

, 18570-19000 cm-1

and 24220-24350 cm-1

assigned to the

transitions 6A 1g

4T1g (

4G)(υ1),

6A1g

4T2g (

4G) (υ2) and

6A 1g

4Eg,

4T1g (

4P) (υ3)

respectively, indicating octahedral geometry30-31

. The observed magnetic moment of the Mn2+

complexes are 5.11-5.13 B.M. corresponding to five unpaired electrons indicates high spin

octahedral environment32

.

Antifungal activity

All the ligands and their complexes are found toxic more or less against fungi. HL2 was more toxic

than HL1. Off all the complexes Copper complex exhibit more toxicity than other metal complexes

against fungi. These results are in agreement with the result obtained by the work of Patel I. J and

Vohra I. M33

. Hence such type of complexes may find as agricultural and garden fungicides.

Conclusion

• The ligand molecule acts as a hexadentate ligand in all the studied cases of complex. Bon

ding either among N(4) depending upon the nature of the metal ions.

• Octahedral structures for Ni2+

, Co2+

and Mn2+

complexes, tetrahedral polymeric structure

for Zn2+

and distorted octahedral for Cu2+

complex have been tentatively proposed. Present

work will contribute in the field of new antifungal for some plant pathogenic organisms.

Acknowledgement

The authors are thankful to Department of Chemistry, Navyug Science College, Surat, for

providing laboratory facilities

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Synthesis, Characterization and Antifungal Activity of Novel … · 2019. 7. 31. · Synthesis, Characterization and Antifungal Activity S447 Synthesis of ligands HL 1 and HL 2 For