26

CHAPTER – II SCHIFF’S BASES AS LIGANDS

2.1 INTRODUCTION Synthesis of new metal complexes of different ligand systems is important

in chemistry, biology and medicine. In recent years, research in the field of

coordination chemistry of biologically important materials has gained

considerable momentum. This is because, metal complexes play vital roles in the

chemistry of living matter. Chlorophyll (a Magnesium complex) in photosynthesis,

Vitamin B12 (a Cobalt complex) in the formation of erythrocytes and haemo

proteins (Iron complex) in respiration are some of the early examples.

Metal complexes derived from heterocycles containing Nitrogen, Sulphur

and Oxygen as ligands have attracted increasing attention in recent years.

Chemical literature provides information on the complexation of transition metals

with ligands having donor atom such as Nitrogen, Sulphur and Oxygen. Many of

the salient features of these Nitrogen and Sulphur complexes have been brought

to light by various researchers in the field [Jungreis E. et al., 1969; Patai Sed.,

1970; Kennedy B.P. et al., 1972; Dutta R.L., 1975; Sibirskaia V.V., 1978; Becher

J. et al., 1982; Shah K.J. et al.,1985; Prisyazhnyuk A.I., 1986; Amina Rai R.A.

and Laxmi, 1986; Mukanti K. et al., 1986; Akbar Ali M. et al., 1986; Ahamad A.S.

et al., 1986; Syamal A. et al., 1986; Shoukry M.M. et al., 1987; Verma J.K., 1987;

Dutton J.C. et al., 1988; Revathy V. et al., 1990; Somasekharappa K.G., 1993].

The metal complexes of Schiff’s bases derived from salicyladehyde or derivatives

of salicyladehyde and the heterocyclic compounds containing Nitrogen, Sulphur

and Oxygen as ligand atoms are of interest, as simple structural models of more

complicated biological systems. Schiff’s bases, having multidentate coordination

sites are attractive analytical reagents, since many of them form complexes with

transition metal ions [Agett J. et al.,1981; Sharma R.C. et al., 1999; Sakyan I. et

al., 2004]. Developing highly functional chelating agents such as Schiff’s bases

has been a great concern of many analytical chemists. Many investigations have

been centered on the structure and bondings in Schiff’s bases, but a few have

27

been directly concerned with analytical applications. Schiff’s bases form

complexes with many transition metals to form either 1:1 (metal:ligand) or 1:2

(metal:ligand) complexes. The analytical methods based on complex formation

are used more frequently. Owing to the relatively simple preparation procedures

of Schiff’s bases, it is possible to obtain ligands of different design and

characteristics by selecting appropriate reactants.

In the subsequent pages of this Chapter, an attempt has been made to

outline a survey of relevant literature regarding the synthesis and analytical

applications of Schiff’s bases. The areas surveyed include formation of Schiff’s

bases, their biological activity, their metal complexes and analytical applications

of Schiff’s bases.

2.2 WHAT IS A SCHIFF’S BASE? A Condensation product of aromatic amines and aldehydes forming

azomethine is called as Schiff’s base. They have general formula RIRIIC=NRIII, where R is aryl or alkyl group. Schiff Hugo Josef in 1864 discovered Schiff’s

base.

2.2.1 Formation of Schiff’s Bases A Schiff’s base or azomethine, is nitrogen analog of an aldehyde or a

Ketone in which the C=O group is replaced by a C=N-R group. It is usually

formed by condensation of an aldehyde or a ketone with a primary amine

according to the following Scheme.

R NH2 + R C R CR

RN R + H2O

Primary amine Aldehyde or ketone Schiff's base

O

R=H

R may be alkyl or aryl group. Schiff’s bases, which contain aryl

substituents, are substantially more stable and more readily synthesized. While

28

those, which contain alkyl substituents are relatively unstable and readily

polymerizable, the aromatic aldehydes having effective configuration are more

stable [Abdul Rauf, 2005].

The formation of the Schiff’s bases from an aldehyde or a ketone is a

reversible reaction and generally takes place under acid or base catalysis.

+ R NH2 R C

NHR

OH

RC RR

O

Ketone or Aldehyde

Carbinolamine

C

NR

R + H2ORN-Substituted imine

(R=H)

The formation is generally driven to completion by separation of the

product or removal of water, or both. Many Schiff’s bases can be hydrolyzed

back to their aldehydes or ketones and amines by aqueous acid or base.

The mechanism of Schiff’s base formation is another variation on the

theme of nucleophilc addition to carbonyl group. In this case, the nucleophile is

the amine. In the first part of the mechanism, the amine reacts with the aldehyde

or ketone to give an unstable addition compound, called carbinolamine and this

subsequently loses water by acid or base catalyzed pathways. Since the

carbinolamine is an alcohol, it undergoes acid catalyzed dehydration.

29

R2C

OH

N

H

R'H+

R2C N

OH2

HR'

C

R

RN R'H

+ H2O

C N

R

R R'+ H3O

(acid catalysed dehydration)

Typically the dehydration of the carbinolamine is the rate determing step

of Schiff’s base formation and this is why acids catalyze the reaction. Yet the acid

concentration cannot be too high, because amines are basic compounds. If the

amine is protonated and becomes non nucleophilic, equilibrium is pulled to the

left and carbinolamine cannot occur. Therefore many Schiff’s base synthesis are

best carried out at mildly acidic pH.

The dehydration of carbinolamine is also catalyzed by base. The reaction

is somewhat analogous to E2 elimination of alkyl halides, except that, it is not a

concerted reaction. It proceeds in two steps through an anionic intermediate. The

Schiff’s base formation is really a sequence of two types of reactions i.e. addition

followed by elimination.

2.2.2 General method for the preparation of Schiff’s Bases The Schiff’s base can be prepared by refluxing equimolar quantities of any

primary amine and the aldehyde or ketone on a water bath for 2-5 hrs. Schiff’s

base thus obtained, is filtered and purified by recrystallisation from the

appropriate solvents (Yield 70-80%). A few examples are given below:

30

Condensation reaction between salicyladehyde and aniline gives Schiff’s

base namely 2-(phenyl imino methyl) phenol [Vogel A.I., 1971].

H2N

OH

O

CH

OH

N+

Salicyladehyde Aniline 2-(phenyl imino methyl) Phenol

Condensation reaction between salicyladehyde and 2-aminobenzothiazole

yields 2-hydroxybenzylidine-2-aminobenzothiazole Schiff’s base. [Popov A.F.

et al., 1989]

OH

CH S

NN

2-Hydroxybenzylidine-2-aminobenzothiazole

Condensation reaction between 2-amino benzothiazole and derivatives of

benzaldehyde gives the Schiff's base [Amany M. Ibrahim, 1993].

S

NN CH

X X=H, p-N(CH3)2, p-OH, o-OH, p-Cl, m-Cl, p-Br, p-NO2

Condensation reaction of 2-hydroxyacetophenone with 1,2′ diamino cyclo-

hexane, 1,2-diphenyl ethylene diamine and 2,2′-diamino-1,1′ bi naphthalene

gives the Schiff’s bases of (I), (II) and (III) respectively [Wen Tao Gao et al.,

2002].

31

C

OH

HN

HO

CNH

C

OH

HN

HO

CNH

HC

OH

N

HO

CHN

(I) (II) (III) Condensing 2-amino benzothiazole with 2-hydroxy-1-naphthaldehyde, 2-

hydroxy benzaldehyde, 4-methoxy benzaldehyde, 4-hydroxy benzaldehyde, and

benzaldehyde (a) and 2-amino-3-hydroxypyridine with 2-hydroxy-1-

naphthaldehyde and 2-hydroxy benzaldehyde (b) gives the Schiff’s bases [Raafat

M. Issa et al., 2008].

S N

N

CR

HN N C

H

R

OH

(a) (b)

(a) R=2-OH-1-naphthaldehyde, o-OH-Ph, p-OCH3-Ph and p-N(CH3)2-Ph.

(b) R=2-OH-1-naphthaldehyde and o-OH-Ph

2.2.3 General properties of the Schiff’s Bases

Pale yellow or orange needles, melting point ranges from 160-240°C,

above this, they undergo decomposition, nearly insoluble in water, but soluble in

aqueous alkaline solution, fairly soluble in benzene, dioxane and chloroform.

They are more soluble in hot ethanol or methanol. Hence these solvents are

generally used for recrystallization. IR spectra of the Schiff’s bases normally

shows C=N stretching frequency between 1562-1650 cm-1 and shift of this band

towards a lower frequency in all Schiff’s base metal complexes suggests that, the

coordination through nitrogen of the azomethine group might have taken place.

32

2.3 SCHIFF’S BASES AS A LIGANDS Ligands which posses two or more donating groups may share more than

one pair of electrons with a single metal ion by coordinating around the central

metal ion. These ligands, generally known as multidentate ligands, are

specifically called bidentate, tridentate etc. Multidentate ligands, which coordinate

with metal ions to form complexes, are also called chelates. Instead of a linear

structure, they have a chelate ring structure.

A common case is where the chelating ligand has at least one acidic

group (-CO2H or -OH) or donor atom, as well as one or more basic atoms like

nitrogen. During the chelation, the acidic group loses a proton and becomes

anionic donor, thus resulting in charge neutralization. The basic nitrogen donates

a pair of electrons to the metal ion. A chelate ligand must possess two acidic or

two coordinating groups or one acidic and one coordinating group. Almost all

organic compounds contain –OH, -SH or –NH groups in some form. Molecules

containing Nitrogen, Oxygen, and Sulphur atoms frequently form coordinate

bonds with metal ions in forming chelate rings. These groups must be located in

the molecule in such positions that, the metal ion will be involved in the ring

formation of five or six atoms. An organic compound containing more than two

donor groups is capable of forming multiple rings with the metal ion resulting in

more stable chelate structure.

The Schiff’s base act as a bidentate monobasic donor for Cu(II), Co(II),

Ni(II), Mn(II) and Fe(II) and prominent sites of coordination are nitrogen of

azomethine group and oxygen of the hydroxyl group. Following are some of the

examples which show the complexing nature of Schiff’s bases.

2.3.1 Monodentate Schiff’s Bases as Ligands Ligands having one atom, which can be an electron donor often, function

as monodentate ligands. Schiff’s base ligand of bis [4-(4-Pyridyl methylene

amino) phenyl] ether (L1) and N,N′-bis (3-pyridyl methyl)-diphthalic diimide) (L2)

act as monodentate ligands. These ligands are used in the preparation of two

supramolecular coordination polymers. Ligand L1 forms an interestingly infinite

cross-linked double helical structure, where as (L2) formes the one-dimensional

33

zig-zag chains, which are parallel with each other. Each ligand coordinates to two

Hg (II) ions and each Hg (II) ion is coordinated by two L2 to generate the

1D zig-zag chains, which are parallel with each other [Xiaokang Li et al., 2007].

N

O

CH

N

N CH

N

CH2N

C CO O

H2C CH2N

N

CH2

L1 L2

bis[4-(4-Pyridyl methylene amino) phenyl] ether (L1)

N,N'-bis(3-Pyridyl methyl)-diphthalic diimide) (L2)

A long, bis (monodentate), linking Schiff’s base ligand L (Py-CH=N-C6H4-

N=CH-Py) (N1 E, N4 E)-N1N4- (Pyridin-3-yl methylene) benzene-1, 4-diamine was

prepared from 1,4-phenylenediamine and 3-pyridine carboxaldehyde by the

Schiff’s base condensation. Ligand L has two terminal pyridyl groups capable of

coordinating to metals through their nitrogen atoms. The Schiff’s base was used

to prepare Zinc coordination polymers. X-ray crystallographic studies proved that

the Zinc metal chelate is coordinated by two Schiff’s base ligands (L) and four

aqua ligands. The geometry of the Zinc metal chelate can be described as a

distorted octahedron, in which the aqua ligands form an equatorial plane [Han Na

Kim et al., 2005].

N N N N

L= (N1 E, N4 E)-N1 N4- (Pyridin-3-yl methylene) benzene-1, 4-diamine.

Few examples for monodentate ligands are listed in Table 2.1

[José A. García-Vázquez et al., 1983; Elerman Y. et al., 1999; Tahereh Sedaghat

et al., 2008; 2009].

34

Table 2.1: Few examples of monodentate Schiff’s bases

Monodentate Schiff’s bases

HO

H3CO

CN

C(CH3)3

C(CH3)3H

(E)-4-[(2,5-di-tert-butyl phenylimino) methyl]-2-methoxy phenol

C

H

N

R R=H, 2Me, 3Me, 4Me, 2,3 Me, 2, 4 Me (E)-N-benzylidenebenzenamine, (E)-N-benzylidene-2-methyl benzenamine, (E)-N-benzylidene-3-methyl benzenamine, (E)-N-benzylidene-4-methyl benzenamine, (E)-N-benzylidene-2, 4-dimethylbenzenamine

C

N

H3CSS

HN C

H

N

(E)-Methyl-2- (2-(pyridin-2-yl methyleneamino) cyclopent-1-enecarbodithioate

MeS

HS

N HOMe SnR2Cl2

n

N

n=1, R=Men=2, R=Bu,Ph

Methyl-2- [2-(acetyl acetoneimino) ethyl amino]-1-cyclopentene-1-dithiocarboxylate Sn (IV)

35

2.3.2 Bidentate Schiff’s Bases as Ligands Ligands having more than one atom, which can be an electron donor often

functions as bidentate ligands. The bis-bidentate ligands were prepared by

condensation reaction between salicylaldehyde and 4,4'-diaminodiphenyl ether.

Complexation of a new bis-bidentate schiff's base, 2-[{{4-[{3-{[(z)-1-(2-hydroxy

phenyl) methylidene] amino} phenyl) oxy] phenyl} imino) methyl]-1-benzenol

(APOPIB) with some mono, di and trivalent metal ions were investigated by the

theoretical calculations and conductance studies. Since APOPIB was able to

form a selective complex with Sm(III) ion (Kf =5.23± 0.24), it was applied

as a sensing material in a poly vinyl chloride (PVC) membrane sensor for

determination of Sm (III) ions [Mohammad Reza Ganjali et al., 2008].

O

N N

OH HO

2-[{{4-[{3-{[(Z)-1-(2-hydroxy phenyl) methylidene] amino} phenyl) oxy]phenyl} imino)

methyl] -1-benzenol (APOPIB)

A few examples for bidentate Schiff’s base ligands are given in Table 2.2

[Mahmoud A.S. Monsm et al., 1996; Viswanathamurthi P. et al., 2005; Siddappa

K. et al., 2008; Prashant Singh et al., 2009].

36

Table 2.2: Few examples of bidentate Schiff’s bases

Bidentate Schiff’s bases

NC

C

N O

H

NH C

S

S CH2C6H5

C6H5

(E)-benzyl-2- [(Z)-2-hydroxyimino)-1,2-diphenylethylidene] hydrazine carbodithioate

H3CN

OH

R [R=Ph, 2-MeC6H4, 4-MeC6H4] (E)-2-[1-(o-tolyl imino) ethyl] phenol, (E)-2-[1-(phenyl imino) ethyl] phenol, (E)-2-[1-(p-tolyl imino) ethyl] phenol

O O

C

O

N

H

N C

HO

CH3

N′- (1-(2-hydroxy phenyl) ethylidene)-2-oxo-2H-chromene-3-carbohydrazide

COOHNS

O

OH 2-Hydroxy-4- {[2-oxo-2-(thiophen-2-yl) ethylidene]amino}benzoic acid [TEAB]

SO

N

HN

O

[N- [2-oxo-2- (thiophen-2-yl) ethylidene] pyridine-3-carboxamide] (TEPC)

37

2.3.3 Multidentate Schiff’s Bases as Ligands Ligands having more than two atoms, which can be electron donors often,

function as multidentate ligands. They are specifically called as tridentate,

tetradentate, pentadentate, hexadentate, heptadentate ligands.

2.3.3.1 Tridentate Schiff’s Base Triaquotribenzo- [b,f,j][l,5,9]–triazacyclodecine Nickel (II) commonly called

(TRI) Ni(OH2)3 2+ is an example of tridentate Schiff’s base complex [Erno B. et al.,

1979].

N N

N

OH2

H2O OH2

Tridentate Schiff’s base Ni(II) complex

2.3.3.2 Tetradentate Schiff’s Base

A tetradentate Schiff’s base was prepared by the condensation reaction

between ethylenediamine and 2-hydroxy-4-methoxybenzophenone. This Schiff’s

base coordinates via the imine nitrogen and enolic oxygen atoms. Their Ni(II) and

Cu(II) complexes adopt a four coordinate square planar geometry, the Vo(IV)

complex is five coordinate square pyramidal and the heteroleptic complexes are

6-coordinate, octahedral geometry [Osowole A.A., 2008].

OH

C NH3C

C

HO OCH3

N

Tetradentate Schiff’s base

38

Tetradentate Schiff’s base Ni(II) complex was synthesized from of

2-hydroxy 1-naphthaldehyde with aliphatic diamines. The mole ratio of Schiff’s

base ligands to the Ni(II) was 1:1 [Byeong-Goo Jeong et al., 1996].

O

HC N CH

O

N

Ni

(CH2)n

Tetradentate Ni(II) complex.

2.3.3.3 Pentadentate Schiff’s Base Pentadentate Schiff’s base ligand, (L) 3,3′-Thiodipropionic acid bis

(4-amino-5-ethylimino-2, 3-dimethyl-1-phenyl-3-pyrazoline) and its complexes

with Co(II), Ni(II) and Cu(II) were reported. [Sulekh Chandra et al., 2009]

N NN N

NMe

Me NH MeHN

N

Et Et

Me

C CO O

S

L 3,3′-Thiodipropionic acid bis (4-amino-5-ethylimino-2, 3-dimethyl-1-phenyl-3-

pyrazoline)

The Schiff’s base bis-[4-hydroxy coumarin-3-yl]-1N,5N-thiocarbo-

hydrazone, was prepared by the reaction of 4-hydroxy coumarin-3-carbaldehyde

with thiocabohydrazide in 2:1 molar ratio. The ligand and its binuclear complex

with Cu(II), Ni(II), Zn(II), Co(II), Mn(II), Fe(III) and Cr(III) ions were also reported

[Abou Melha K.S. et al., 2008].

O O

N

OH

N NN

O

H H

SO

OH

bis-[4-hydroxy coumarin-3-yl]-1N,5N-thiocarbohydrazone

39

2.3.3.4 Hexadentate Schiff’s Base Hexadentate Schiff’s base ligand (L) was prepared from the reaction of

two moles of 2-benzoyl pyridine and one mole of triethylene tetramine and its

Nickel complex was prepared and characterized by single crystal X-ray diffraction

studies. Each Nickel center is coordinated in a distorted octahedral fashion

consisting of three nitrogen atoms from the hexadentate ligand moiety, two

nitrogen atoms from two azido ligands and the last one from another terminal

azido ion [Soma Deoghoria A. et al., 2003].

N

C N NH

NH

N C

NL Hexadentate ligand

2.3.3.5 Heptadentate Schiff’s Base Heptadentate Schiff’s-base ligands tris[3-(salicylideneimino) propyl] amine

and tris [3-(4′-hydroxysalicylidene imino)-propyl] amine were by the condensation

reactions of tris(3-aminopropyl)amine with 3 equivalents of either salicylaldehyde

or the ring substituted salicylaldehyde, 4-hydroxy salicylaldehyde. Their nickel (II)

and copper(II) complexes were also synthesized [Hassan Keypour et al., 2002].

Heptadentate Schiff’s base metal complex

40

Schiff’s base ligands are capable of forming five or six membered chelate

rings resulting in a more stable chelate structure, which leads to the formation of

mixed ligand complexes. They often provide special sensitivity and selectivity for

analytical importance. Due to the great flexibility and diverse structural aspects of

Schiff’s bases, wide ranges of these compounds have been synthesized and

their complexation behaviors studied.

2.4 BIOLOGICAL ACTIVITY OF SCHIFF’S BASES Schiff’s bases and their metal complexes are extensively studied due to

synthetic flexibility, selectivity and sensitivity towards a variety of metal ions.

They are found useful in catalysis, in medicine as antibiotics and anti-

inflammatory agents and in the industry as anticorrosion agents [Mehta N.K. et

al., 1996; Sun B. et al., 2001; Britovsek G.J.P. et al., 2001; Boghaei D.M. et al.,

2002; Jin V.X. et al., 2005; Liu J. et al., 2006; Budakoti A. et al., 2006]. Schiff’s

base complexes are also noted for their significant antifungal and anti bacterial

activities. Nitro and halo derivative of Schiff’s bases are reported to have

antimicrobial and antitumor activities [Giordano R.S. et al., 1974].

A new anticarcinogenic agent of thiazole Schiff’s base like

N-Benzylidene thiazole-2-amine was prepared by condensation reaction between

2-amino thiozole and aromatic aldehydes. Reason for the biological activity of the

compound was discussed based on the presence of azomethine linkage and of

the thiazole moiety [Mazumdar A.K.D. et al., 1979].

N

SN C

H

N-Benzylidene thiazole-2-amine

Schiff’s bases derived from 4-aryl-2-aminothiazole and 2-amino

benzothiazole with salicyladehyde, 4-aryl-2-(2′-hydroxy aryl imino methyl)

thiazole methiodides, 4-aryl-2- (2′-hydroxy-α- substituted benzyl amino)-thiazoles

and 2-(2′-hydroxy phenyl or naphthyl)-3-(4′-aryl thiazol-2′-yl)-4-thiazolidones were

41

synthesized and biological screening studies of the Schiff’s bases and their metal

complexes reported [Dash B. et al., 1980].

Schiff’s bases derived from 4-substituted, 4,5-disubstituted-2-amino-

thiazoles, substituted 2-aminobenzothiazoles and p-hydroxy benzaldehydes were

synthesized. These compounds were characterized by elemental analysis, IR

and mass spectra and screened for their fungicidal activity [Dash B. et al., 1984].

Bidentate Schiff’s bases of 2-amino benzothiazole with 2-hydroxy-1-

naphthaldehyde [(E)-1-((benzo [d] thiazol-2-ylimino) methyl) naphthalene-2-ol]

were synthesized and their Chromium(III) complexes were screened for

microbiological activity against the fungi Aspergillus niger, Alternaria alternate

and bacterium Escerichia coli [Mishra V. and Saksena D.K., 1987].

S

NN

OH

(E)-1-((benzo [d] thiazol-2-ylimino) methyl) naphthalene-2-ol

Mixed ligand transition metal complexes of Schiff’s bases were

synthesized and anti bacterial, antifungal activities were evaluated including

toxicological studies [Saidul Islam M. et al., 2001]. Co (II) and Ni (II) complexes

with a Schiff’s base, N-(2-furanyl methylene)-2-amino thiadiazole were prepared

and characterized. These Schiff’s bases and their complexes were screened for

antibacterial activity against bacterial stains, e.g. Escherichia coli,

Staphylococcus aureus and Pseudomonas aeruginosa [Zahid H. Chohan et al.,

2002].

N

O

N N

S

N- (2-furanyl methylene)-2-aminothiadiazole

Benzoisothiazole, benzothiazole and thiazole Schiff’s bases were

synthesized and tested for invitro studies with the aim of identifying novel lead

42

compounds which are active against human and cattle infectious diseases or

against drug resistant cancers for which no definite cure or efficacious vaccine is

available at present. In particular, these complexes were evaluated for invitro,

activity against representatives of different virus species, such as Yellow fever

virus and bovine viral diarrhoea virus and it is also tested for gram positive and

negative bacteria [Vicini Paola et al., 2003].

Schiff’s base derived from 4-aminobenzoic acid was used for antibacterial

activity [Jigna Parekh et al., 2005]. A Series of Schiff’s bases were synthesized

by the condensation reaction of 2-amino nicotinic acid with salicyaldehyde,

5-bromo salicyladehyde, 5-nitrosalicyladehyde and 5-methoxy salicyladehyde,

condensation reaction of 2-amino-1,3,4-thiadiazole with the furfuraldehyde,

thiophene-2- carboxaldehyde and pyrrole-2-carboxaldehyde. Condensation

reaction of 5-amino-1,3,4-thiadiazole-2-thiole with furfuraldehyde, thiophene-2-

carboxaldehyde, 4-bromothiophene-2-carboxaldehyde, pyrrole-2-carboxaldehyde,

salicyladehyde and pyridine-2-carboxaldehyde and their antibacterial activities

were reported [Abdul Rauf, 2005].

Co(II), Ni(II), Cu(II) and Zn(II) Vanillidene alanine complexes were

synthesized, characterized, their geometry and the ferromagnetic nature, X-ray

powder diffraction and biological activity studies were reported[Selwin Joseyphus

R. et al., 2006].

4-Ethyl-6-{(E)-1-{(3-nitrophenyl) imino] ethyl} benzene-1, 3-diol and their

metal complexes were prepared and their antibacterial activitity studied on

bacteria Pseudomonas vulgaris [Nair R. et al., 2006].

Ni(II) Schiff’s base complex, derived from salicyladehyde and o-amino

benzoic acids were tested for their antibacterial activities against several human

pathogenic bacteria [Morad F.M. et al., 2007].

COOH

N C

HHO

2-(2-hydroxy benzylidene amino) benzoic acid

43

Coordination complexes of Cu(II), Co(II), Ni(II), Mn(II) and Fe(II) with

Schiff’s bases derived from 3-(4-Chlorophenoxy methyl)-4-amino-5-mercapto-

1,2,4-triazole and salicyladehyde were synthesized and characterized. The

antibacterial activities of these Schiff’s bases and their metal complexes were

screened by cup plate method [Vidyavathi Reddy et al., 2008].

Schiff’s base of dapsone and 2-azetidinones of 4,4′-diaminodiphenyl

sulphone were synthesized. 4,4′ –diamino diphenylsulphone was condensed with

various aromatic or heterocyclic aldehydes in ethanol in the presence of

concentrated sulphuric acid as a catalyst to yield the Schiff’s base. These Schiff’s

bases on treatment with chloroacetylchloride in the presence of triethylamine,

gave substituted 2-azetidinone, which was evaluated for the invitro activity

against several microbes [Wadher S.J. Puranik et al., 2009].

H2N NH2 + R CO

2 H

Reflux

N NS CH RHCR

Chloroacetyl chlorideTriethylamineSchiff's base (1)

N NSHC R

O X

HCR

X O Azetidinone(II)

DapsoneAldehyde

SO

O

O

O

O

O

X= Cl, F, -OMe, -NO2

Synthesis of Schiff’s base and azetidinone, R=aromatic group

Schiff’s bases were synthesized by the reaction of naphtha [1,2-d] thiazol-

2-amine with various substituted aromatic aldehydes. 2-(2′-Hydroxy) benzylidene

aminonaphtha thiazole was converted to its Co(II), Ni(II) and Cu(II) metal

44

complex on treatment with metal salts in ethanol. All the complexes were

evaluated for their antibacterial activities by paper disc diffusion method with

Gram-positive Staphylococcus aureus, Staphylococcus epidermidis and Gram-

negative Escherichia coli and Pseudomonas aeruginosa bacteria. The minimum

inhibitory concentrations of all the Schiff’s bases and metal complexes were

determined by agar streak dilution method. All the compounds moderately

inhibited the growth of Gram-positive and Gram-negative bacteria. Schiff’s base

2-(2′-hydroxy) benzylidene aminonaphtho thiazole showed maximum inhibitory

activity and among metal complexes, Cu(II) metal complex was found to be most

potent. The results also indicated that, the metal complexes are better

antibacterial agents as compared to the Schiff’s bases [Faizul Azam et al., 2007].

2.5 SCHIFF’S BASE METAL COMPLEXES Schiff’s base metal complexes are very important in coordination

chemistry due to their facial synthesis, involvement in catalytic processes and

discovery that the proteins and enzymes require two or more metal ions for their

activity. Schiff’s bases have remarkable property of forming complexes. Several

reports are available only for the synthesis, characterization of Schiff’s bases and

their metal complexes.

Schiff’s base derived from the self-condensation of o-aminobenzaldehyde

was used for the preparation of Nickel (II) complex [Larry T. Taylor et al., 1969].

N

C

CH

N C

HN

H

N

CH

Ni

Nickel complex of Schiff's base derived from self-condensation of

o-aminobenzaldehyde

45

Dash et al synthesized and studied the structural features of Co(II), Ni(II),

Cu(II) and Zn(II) complexes of Schiff’s bases derived from 4-aryl-2-aminothiazoles

and salicyladehyde [Dash B. et al., 1980].

C

HC

R

SC

N

N

MO

C

H

M=Co(II), Ni(II), Cu(II), Zn(II), R=H, Cl, CH3, OCH3, C2H5

Schiff's base metal complexes derived from 4-aryl-2-aminothiazoles and salicyladehyde

Schiff’s bases synthesized by condensation of salicyladehyde and

2-amino-4-phenyl-5-arylazothiazoles and their metal complexes with Pd(II),

Rh(III), Ru(III), Fe(III) were characterized and their structural studies were

reported [Sharma C.L. et al., 1986].

Ligand 5-bromo-2-hydroxy benzylidine-2-amino benzothiazole and its

complexes with Co(II), Cu(II) and Ni(II) were synthesized and characterized. It

was suggested that, two ligands with water molecules coordinate to each metal

atom by hydroxyl oxygen and imino nitrogen to form high spin distorted

octahedral complexes with Co(II), Ni(II), and Cu(II) [Saydam S. et al., 2001].

S

N

N

M O

N

N

SO

OH2

H2O

Br

Br

M=Co(II), Ni(II), Cu(II) Metal complexes of 5-bromo-2-hydroxy benzylidine-2-amino benzothiazole

46

Cu(II), Ni(II), Mn(II), Zn(II) Schiff’s base complexes derived from

o-phenylendiamine and acetoaetanilide were synthesized and characterized,

magnetic susceptibility data and conductance values were reported [Raman N.

et al., 2001].

N

N

N Me

O

H

N Me

O

H

M

H

H

Ph

Ph

M=Cu(II), Ni(II), Mn(II), Zn(II)

Schiff’s base metal complexes derived from o-phenylendiamine and acetoaetanilide

Cu(II), Co(II) and Mn(II) complexes of Schiff’s base ligand derived from

2,2′-bis(p-methoxyphenylamine) and salicyladehyde were synthesized and

spectral properties and electrochemical behaviors investigated [Xishi Tai et al.,

2003].

N N

OOM

M=Cu(II), Co(II), Mn(II)

Metal complexes of Schiff’s base ligand derived from 2-2′-bis(p-methoxy

phenylamine) and salicyladehyde

Cu(II), Mn(II), Ni(II) and Zn(II) metal complexes with novel

heterocyclic Schiff’s bases derived from 5-Phenyl azo-salicyladehyde and

o-amino benzoic acid were synthesized, characterized. These Schiff’s bases

behave as neutral tri dentate ligands forming chelates with (1:1) metal ligand

stoichiometry [Refut M.S. et al., 2006].

47

2.6 SCHIFF’S BASES AS ANALYTICAL REAGENTS Schiff’s bases chelate with many transition metals either in weakly acidic

medium or in weakly alkaline medium to form either 1:1 (metal: ligand) or 1:2

(metal: ligand) complexes. Hence Schiff’s bases derived from aromatic amines

and aromatic aldehydes have wide variety of applications in many fields. Schiff’s

bases are attractive as analytical reagents because, they enable simple and

inexpensive determination of various organic and inorganic substances. In

general, there are two principal ways of their analytical applications: first

determination of organic compounds bearing an amino or an active carbonyl

group by the formation of coloured (Chromophore containing), fluorescent or

insoluble Schiff’s bases and secondly, the determination of various metal ions as

well as amino and carbonyl compounds, using complex formation reactions. The

analytical methods based on complex formation are used more frequently. Owing

to the relatively simple preparation procedures of Schiff’s bases, it is possible to

obtain ligands of different design and characteristics by selecting appropriate

reactants.

Glyoxal bis(2-hydroxyanil) was used as a sensitive reagent for the

determination of calcium and also used as metal indicator in the chelatometric

titration of Calcium. The reagent behaves as quadridentate ligand, forming a 1:1

chelate [Lapin L.N. et al., 1958; Gavrilova L.G. et al., 1970; Honjo et al., 1978]. O

N

O

N

CHCH

M

Glyoxal bis (2-hydroxyanil)

Schiff’s base reagents derived from pyridinaldehyde, pyridine -2-aldehyde-

2′-pyridyl hydrazone and pyridine-2-aldehyde-2′-quinolylhydrazone were used as

extraction photometric reagents for the determination of Pd(II) and for Cu(II) [Bell

C.F. et al., 1965]. The only disadvantage of this reagent in comparison with

cuprion reagent was the lack of selectivity [Cameron A.J. et al., 1968; Sims G.G.

et al.,1969; Zatka V. et al., 1971].

48

Schiff’s bases of o-hydroxy aromatic aldehyde (salicyladehyde) with

aliphatic and aromatic mono and diamines (1,2-benzene diamine, aniline,

2-aminophenol and their derivatives) which were used in the determination of

Cu(II), Be(II), Mg(II), Ca(II), Al(III), Ga(III), Sc(III), Mn(II), Fe(III), U(VI) [Jungreis

E. et al., 1969; Morishige K., 1978; Cheng K.L. et al., 1982; Ren K., 1993].

These Schiff’s bases are used as volumetric, gravimetric, fluorimetric,

spectrophotometric reagents.

Schiff’s base of salicylidene-o-aminophenol and Schiff’s base

2-hydroxyaniline-N-salicylidene were used to study the fluorescence properties of

some metal complexes of Zinc, Tin, Scandium, Aluminium, Galium [Kiyotoshi

Morisige, 1978, 1980]

HC OHN OH

2-Hydroxyaniline-N-salicylidene

Aromatic 2-hydroxy aldehyde was condensed with a number of aliphatic

and aromatic amines to form a series of bi, tri and tetra dentate Schiff’s bases

like bis-salicylidene-o-phenylenediamine, salicylidene ethylimine, N,N′-bis

(salicylidene)-2,3-diamino benzofuran and salicylidene anthranilic acid. These

were used as highly sensitive extraction photometric reagents for Cu(II)

(extraction with chloroform, methyl isobutyl ketone and toluene) [Agett J. et al.,

1981].

3-Hydroxy picolinaldehyde Azine was used as photometric reagent for

Ag(I), Cu(II), Hg(II), Pt(IV), Co(II), Ni(II), Zn(II), Pd (II), Cd(II), Mn (II) and Fe(II, III)

[Cheng K.L., 1982].

N

OH N

OH

NN

3-Hydroxypicolinaldehyde Azine

49

N,N′-bis (3-carboxysalicylidene) trimethylenediamine was used for the

determination of trace amounts of Mercury by anode stripping voltammetry

method and the method was used for the determination of mercury in natural

water samples [Kuai-Zhi Liu et al., 1990].

Heteroaromatic Schiff’s bases, 2-(3-pyridyl methyl iminomethyl) phenol,

2-(2-pyridyl iminomethyl) phenol, 2-(2-amino-3-pyridyl iminomethyl) phenol,

N,N′-bis (salicylidene)-2,6-pyridine diamine and 2-(2-amino-4-methoxymethyl-6-

methyl-3-pyridyl methyl imino methyl) phenol were used as reagents for the

spectrophotometric and spectrofluorimetric determination of Copper by extraction

method. The spectrophotometric determination of Cu(I) after extraction was very

sensitive and selective with regard to Cd(II) and Pb(II). Highest sensitivity was

achieved with compound 2-(2-amino-4-methoxy methyl-6-methyl-3-pyridyl methyl

imino methyl) phenol [Zvjezdana Cimerman et al., 1997]. OH

N

N

OH

NN

NH2 2-(3-pyridyl methyl imino methyl) phenol, 2-(2-amino-3-pyridyl imino methyl) phenol

OH

N

N

N

NN

OH

OH

2-(2-pyridyl imino methyl) phenol, N, N′-bis (salicylidene)-2,3-pyridinediamine

NN N

OH

OH NH3C

CH2OCH3

NH2

N

OH

N,N′-bis(salicylidene)-2,6-pyridinediamine, 2-(2-amino-4-methoxy methyl-6-methyl-3-

pyridyl methyl imino methyl) phenol.

50

Schiff’s base of N-furoylphenyl hydroxyl amine forms complexes with

Co(II), Cu(II), Zn(II) and Fe(II). The reagent is used for the gravimetric

determination of Co(II), Cu(II), Zn(II) and Fe(II) through the precipitation of their

complexes. [Moustafam M. et al., 1997]

The Schiff’s base 2-(2-pyridyl methylene amino) phenol (PMAP) was

investigated as a spectrophotometric reagent for the determination of Iron in

caustic soda, cotton yarn and fabric, woolen fabric and industrial water [Grabaric

Z. et al., 1999].

OH

N

N 2-(2-pyridyl methylen amino) phenol

Nickel was determined by flow injection spectrophotometry at 370 nm after

extraction of Nickel(II)bis(acetylacetone)ethylenediaminate chelate into

chloroform using phosphate buffer (pH 7). Calibration graph was linear up to

25µg mL-1 Nickel. The system was applied to the determination of Nickel in

Nickel-Copper alloys and in synthetic electroplating solutions [Chimpalee N.

et al., 2000].

Salicylhydrazidone-2′-Hydroxy acetophenone was used as the spectro-

photometric reagent for the determination of Al(III) at pH 4.6 and was also used

for the determination of microgram quantities of sulfanilamide [Raluca Mocanu

et al., 2000].

Schiff’s base metal complexes of N,N′-cis-1,2-cyclohexylene bis

(salicylideneaminato) Cobalt(II), [Co(II)(c-Salcn)] and N′-(±)-trans-1,2-cyclo-

hexylenebis(salicylideneaminato)Cobalt(II), [Co(II)(t-Salcn)] were synthesized

and characterized by elemental analysis, Melting points, IR, electronic, and 1H

and 13C NMR spectra. Their thermo gravimetric studies were also discussed

[Felicio R.C. et al., 2001].

51

Salen-type Schiff’s base is obtained by condensing ethyl-o-hydroxy-

benzene with ethylene diamine and 1-ethyl-salicylidene bis ethylene diamine.

This reagent was used as spectrophotometric reagent for the determination of

Mn(II) to a concentration range of 10-70 µg/mL. This method was successfully

applied for the determination of to Mn(II) present in pharmaceutical products

[Tantaru Gladiola et al., 2002].

Schiff’s bases synthesized by the condensation reaction between

5-[3-(1,2,4– triazolyl-azo]-2,4-dihydroxy benzaldehyde with 1,3-diaminopropane

and 1,6-diaminohexane were used for the spectrophotometric determination of

Cobalt (II) [Khedr Abdalla M. Gaber Mohamed et al., 2005].

Sensitive chromogenic reagent N,N′-bis(3-methylsalicylidene)-ortho

phenylene diamine was used in the spectrophotometric determination of Nickel.

At pH 8 the ligand reacts with Nickel to form 1:1 complex. The method was

successfully applied for the determination of trace amounts of Nickel in some

natural food samples [Ali Reza Fakhuri et al., 2005].

N

NHO

H3C

OHH3C N, N′-bis (3-methyl salicylidene)-ortho phenylene diamine

Schiff’s bases derived from 2-thiophene carbaldehyde with 2-amino-

thiazole were used for the spectrophotometric determination of Ni(II). The

method was applied for the determination of Ni(II) in various synthetic and natural

samples [Maria Pleniceance et al., 2005].

2-Ethanolimino-2-pentylidino-4-one Schiff’s base derived from mono-

ethanolamine and acetyl acetone was used as spectrophotometric reagent for

the determination of Fe(III), Cu(II), and UO2(II). Fe(III) complex was detected at

λmax 440 nm, (pH 3.5), Cu(II) complex at λmax 340 nm (pH 6) and UO2 complex at

52

λmax 370 nm (pH 4). Beer Lambert’s law obeyed in a concentration range of

0.5 to 3.0 x10-4 [Adel S. Orabi et al., 2005].

N,N′ bis-salicylidene-o-phenylene di imine was used as analytical reagent

to determine trace concentration of metal ions like Fe(II), V(II) and Co(II) by

spectrophotometric method [Naser Eltaher Eltayeb et al., 2005].

Two new chemically modified silica gel covalently bonded with 4,4′-

diaminodiphenyl ether (DDE), 4,4′-diaminodiphenyl sulfone salicyladehyde

Schiff’s bases were synthesized and were characterized by FTIR and BET

surface area measurement techniques. These synthesized chelating materials

were tested for the pre concentration of metal ions like Zn(II), Mn(II), Cr(III) in

batch and column techniques with variation in parameter in competitive and non

competitive conditions. The method was found very useful in recovery of the

metal ions from dilute aqueous solutions [Dey R.K. et al., 2006].

Schiff’s bases prepared by the condensation of aromatic mono and

diamines derivatives and were used as fluorometric analytical reagents

[Mohamed N. Ibrahim et al., 2007].

Extractive spectrophotometric determination of Ca(II), Mg(II), Cr(III),

Fe(II), Zn(II), Cd(II), Ni(II), Mn(II), and Co(II) were done using some chiral Schiff’s

bases Benzaldehydene-(S)-2-amino-3-phenyl propanol (I), o-hydroxy

benzaldehydene-(S)-2-amino-3-phenyl-propanol (II), Benzaldehydene-(S)-2-

amino-3-methylbutanol (III) as complexing agents [Giray Topal et al., 2007].

CH N

OH

H

CH N

OH

H

OH

H3CCH3CH N

OH

H

OH

(I) (II) (III)

Schiff’s bases derived from aromatic aldehydes namely Vanillin and

p-dimethyl amino benzaldehyde were used for the spectrophotometric

determination of metronidazole in tablets [Siddappa K. et al., 2008].

53

2.7 CONCLUSIONS The Schiff’s bases are among the most widely used ligands due to their

facile synthesis, remarkable versatility and good solubility in common solvents.

Thus, they have played an important role in the development of coordination

chemistry, as they readily form stable complexes with most of the metals. The

research field dealing with Schiff’s base metal complexes is very broad due to their

potential interest for a number of interdisciplinary areas including bioinorganic

chemistry, catalysis and magneto chemistry. In the area of bioinorganic chemistry,

the interest in the Schiff’s base complexes lies with the synthetic models for the

metal containing sites in metalloproteins and enzymes [Ouyang X.M. et al., 2002;

Jayabalakrishnan C. et al., 2002; Sharghi H., 2003; Cozzi P.G., 2004; Shalin

Kumar et al., 2009]. Therefore several reports are available only in synthesis and

characterization of Schiff’s bases.

Various Schiff’s bases of aromatic amines and aromatic aldehydes have a

wide variety of applications in many fields like biology, inorganic and analytical

chemistry. They are used in optical and electrochemical sensors as well as in

various chromatographic methods, to enable detection with selectivity and

sensitivity [Lawrence J.F. et al., 1976; Valcarcel M. et al., 1994; Spichiger-Keller

U., 1998].

Among the organic reagents, actually used Schiff’s bases show excellent

characteristics, structural similarities with natural biological substances with

relatively simple preparation procedures and synthetic flexibility accompanied

with suitable structural properties. [Jungreis E. et al., 1969; Patai Sed, 1970]

Schiff’s bases derived from thiazoles and benzothiazoles have been

widely used as antifungal, antibacterial and anticancer agents. This versatile

bioactivity is due to presence of multifunctional groups [Ivanovskii V.I., 1978;

Venugopala K.N. et al., 2003; Vashi K. et al., 2004; Tellez F. et al., 2004; Chohan

Z.H. et al., 2004].

Benzothiazoles are used for the production of dyes with photosensitizing

properties [Kiyotoshi Morisige, 1980]. A number of researchers have carried out

the research with o-Vanillin and 2-aminobenzothiazoles metal complexes [Giusti

54

A. et al., 1982; Sokolowska Gajda J. et al., 1992; Velcheva E.A. et al., 2004;

Tellez F. et al., 2006; Yin H.D. et al., 2006]. But Schiff’s base of 2-amino

benzothiazole and its derivatives with o-Vanillin and the metal complexes along

with the use of these Schiff’s bases as analytical reagent was not done. This

stimulated our research interest in the present investigation.

Synthesis and characterization of Schiff’s bases derived from 2-amino

benzothiazole, 2-amino-4-methylbenzothiazole, 2-amino-6-chlorol benzothiazole

and 2-amino-6-bromo benzothiazole with o-Vanillin and their Copper complexes

are done in the present work. Also new spectrophotometric methods for the

determination of Copper ions from these Schiff’s bases were designed. This

method was successfully applied for the estimation of trace amounts of Copper

ions from the industrial effluents.