CHAPTER - 1

Introduction

1.1 Inorganic Chemistry and Coordination Compounds

1.2 Synthetic Strategies - The Mannich Reaction

1.3 Metal Complexes of Acetamide and Related Derivatives

1.4 Metal Complexes of Acrylamide and Related Derivatives

1.5 Metal Complexes of Benzamide and Related Derivatives

1.6 Mannich Bases and Related Metal Complexes Synthesized in Our

Laboratory

1.1 Inorganic Chemistry and Coordination Compounds

The field of coordination chemistry has grown fi:om a readily defined and limited area

into what is now the most active research field of inorganic chemistry encompassing a great

variety of subjects and phenomena. The study of coordination compounds has always been a

challenge to inorganic chemists. It seemed difficult and vague in early days and hence the

name "complex".

Historically, the accumulations of information and experimental data about this class

of compounds have been very slow and gradual. The developments in this field dates back to

the era of French Revolution. In that period, people isolated several natural dyes and later

they were found to be typical coordination compounds. The bright red alizarin dye , a

calcium aluminium chelate of hydroxyl anthraquinone is one of the best example. Probably

the first scientifically recorded observation of a completely inorganic coordination compound

is the formation of the familiar tetramminecopper(II) ion .

The discovery of the first metal ammine compoimd is attributed to Tassaert.

He prepared hexamminecobalt(III) chloride, [Co(NH3)6]Cl3, the parent compound fi-om which

all the other cobalt ammines have been derived later. An mteresting compound which played

an important role in the development of bonding theory is

potassiumtrichloro(ethylene)platinate(II) monohydrate, which was discovered by

William Christoffer Zeize. However, its structure and bonding were not understood until the

synthesis of the first sandwich compound, ferrocene.

Coordmation complexes may be defined as a molecule or ion in which there is a metal

atom wliich is closely attached to other atoms or groups. The metal is called the centre of

coordination and the groups attached to it are called ligands. The total number of such ligands

around the central metal ion decides its coordination number and these altogether constitute

the coordination sphere. The ligand is said to be a chelate if it possesses more than one

coordinating atom. The complex may be cationic, anionic or neutral depending on the charges

carried by the central metal atom and the ligands. The essential feature of a coordination

compound is that it retains its identity even in solution, though partial dissociation may occur.

The early studies on inorganic complex compounds consisted largely a series of

attempts to explain the structure and stability of hydrates, double salts and metal ammonia

compounds. Gibbs and Genth deserve all credits for attracting chemists to a field which today

is experiencing a renaissance of activity. Their experimental results form a direct transitional

link from the prunitive, qualitative observation of Libavius. Diecbach and Tassaert to the

most recent sophisticated, quantitative contemporary investigations. As the number of

known coordination compounds increased, theories to explain their constitution were also

devised .

Thomas Graham is credited with the discovery of the first theory of metal ammines,

the so called "Ammoniirai Theory", which shows a remarkably close similarity to the modem

Lewis acid-base approach to coordinated covalent bonds. Later large modifications were

proposed by other chemists such as, Gerhardt, Wurtz, Reiset, Van Hoffinan and Weltzien.

The most successfiil and widely accepted pre Werner theory was the "Chain Theory"

advanced by Christian Wilhelm Blomstrand and later developed by Jorgensen. His

experiments have proven completely reliable and provided the experimental foimdation not

only for the Blomstrand-Jorgensen chain theory but also for Werner's coordination theory'*.

All these early theories are of little more than historical interest. However, the

coordination theory proposed by Alfred Werner'* marked an abrupt break in the classical

theories of valence and structure. He postulated two types of valences, primary or ionizable

valence and secondary or non-ionizable valence. Every metal in a particular oxidation state

has a definite coordination number. Even though the primary valence can be satisfied by only

anions, secondary valence can be satisfied not only by anions but also by neutral molecules.

The secondiary valences are directed in space around the central metal atom. However, he had

no theoretical justification for the two types of valences. The important thing concerned with

a coordination complex is the way in which we describe and characterize the bonding

between central metal ion and the ligands. The first successful application of bonding theory

to complexes is due origmally and mainly to Pauling . It is usually referred to as valence bond

theory. It deals with the electronic structure of the ground state of the metal atom and is

concerned primarily with the kind of bonding, stereochemistry and gross magnetic properties

of complexes. In valence bond theory, it has been assumed that all ligands are good Lewis

bases. However, it is far from the true situation. Later other methods, such as the crystal field

theory, based on electrostatic approach and the molecular orbital theory, based on quantum

mechanics helped to correlate the electronic structure and configuration of complexes with

their physical and chemical properties.

Crystal Field Theory (CFT) is a model that describes the electronic structure of

transition metal compoimds, all of which can be considered coordination complexes. CFT

successfully accounts for some magnetic properties, colours, hydration enthalpies, and

structures of transition metal complexes, but it does not attempt to describe bonding. CFT was

developed by physicists Hans Bethe and John Hasbrouck Van Vleck in the 1930s. CFT was

subsequently combined with molecular orbital theory to form the more realistic and complex

Ugand field theory (LFT), which delivers insight into the process of chemical bonding in

transition metal complexes^^,

Ligand field theory' (LFT) describes the bondmg in coordination complexes.

It represents an application of molecular orbital theory to transition metal complexes.

A transition metal ion has six hybridized orbitals of equal energy to engage its ligands. The

LFT analysis depends on the geometry of the complex, but for explanatory purposes, most

analyses focus on octahedral complexes, where six ligands coordinate to the metal * .

MO theory provides a global, delocalized perspective on chemical bonding.

For example, in the MO theory for hypervalent molecules, it is no longer necessary to invoke

a major role for d-orbitals. In MO theory, any electron in a molecule may be found anywhere

in the molecule, since quantum conditions allow electrons to travel under the influence of an

arbitrarily large number of nuclei, so long as permitted by certain quantum rules. Although in

MO theory some molecular orbitals may hold electrons which are more localized between

specific pairs of molecular atoms, other orbitals may hold electrons which are spread more

unifonnly over the molecule. Thus,.overall bondings (and electrons) are far more delocalized

(spread out) in MO theory, than is implied in VB theory. This makes MO theory more useful

for the description of extended systems''.

New procedure for the synthesis of inorganic complexes has made it possible to

prepare several new types of compounds. The template methods of forming multidentate

cyclic complexes were previously unknown and unavailable. In this context the contribution

by Shibata and coworkers'^ are particularly important.

Since early workers on coordination chemistry focused their whole attention on the

theoretical aspects, practical applications of coordination compounds received little attraction.

However, in recent times, their applications have developed to a great extent. Perhaps the

most important of this is in catalysis. Platinum complexes have found place in the chemical

industry as stereo specific catalysts and this is important in the manufacture of some drugs.

The interest in the role of metal ions in biological process has stimulated work in bioinorganic

chemistry' . Alkali and alkaline earth metal complexes with crown ethers and other cyclic

ligands play unportant biological roles. Metal chemotherapy and chelation therapy have now

drawn attention as additional outlets for coordination chemistry. Thus no doubt, all these

investigations wall be found valuable for better clarification of various processes in life as

well as in almost all other fields. Early workers considered coordination compounds of only

a few metals and with common coordination numbers such as, 4 and 6. More recent research

activities on coordination compounds are concerned with nearly all the metals in the periodic

table in many oxidation states and with all the possible coordination numbers fi:om 2 to 12.

The investigations in coordination chemistry make use of powerful

physico-chemical methods of structure determination. They include routine techniques, such

as IR, UV-Visible, NMR, EPR and Mass spectral and especially single crystal X-ray

diffraction studies. Thus with the combined use of these modem methods much information

about the nature of complexes may be gathered.

1.2 Synthetic Strategies - The Mannich Reaction

The Mannich reaction is a three component condensation in which a compound

containing an active hydrogen atom (substrate) is allowed to react with formaldehyde and an

NH- amine derivative.

The first 'Mannich reaction' took place accidentally in 1912, when Carl Mannich, a

young Professor in the pharmaceutical laboratory at Gottingen University, was treating with a

acid solution of a pharmaceutical preparation based on salicylantipyrine and urotropine

(hexamethylenetetramine). He obtained a crystalline precipitate, which was later identified in

collaboration with Krogen Kroshe, as having the structure^^ shown in (Fig.I.l).

Having observed that the same condensation product was also formed by mixing

antipyrine, formaldehyde and ammonium chloride, regardless of the order of addition,

Mannich realized the great synthetic relevance of the reaction of which only a few examples

were known in the literature at that time. He saw that it allowed the linkage of two different

chemical moieties in one step by means of a methylenic bridge. He, then studied the reaction

in considerable depth, assisted by a number of collaborators, and demonstrated its general

applicability as a method for obtaining aminomethylated products. Mannich published more

than sixty papers on this topic, one fifth of his wide scientific production. Since then,

Mannich bases have been subjects of growmg interest as evidenced by the appearance of a

number of books and comprehensively reviewed papers. Recently some review articles have

appeared in which several applications of Mannich bases in the pharmaceutical field and in

other industries such as those connected with macromolecular chemistry are described. More

recently, a book with emphasis on the wide range of practical applications by using the

chemistry of Mannich bases authored by Tramontini and Angiolini''* has been published.

In view of the huge extent of literature available and the need to keep this chapter to a

reasonable size, we are constrained to be selective in our citations.

. N .

CHj I

N , ;N

Hexamethylenetetramine

S alicy lantipy rine

+HN M B \

\ Me

Fig.I.l The First Mannich Reaction

Synthesis of Mannich Bases

The Mannich reaction is the prototype of carbon-carbon bond forming reactions that

involve the addition of resonance stabilized carbon nucleophiles to immonium salts and

imines. hi its original and most widely recognized form, Mannich reaction is a three

component condensation of

i) ammonia or a primary amine or a secondary amine;

ii) a non-enolizable aldehyde, usually formaldehyde; and

iii) a compound containing an active hydrogen atom (substrate).

These three compounds condense with concomitant release of water to produce a new

base knovra as a Mannich base, in which the active hydrogen is replaced by an aminomethyl

group.

The formation of both carbon-carbon and a carbon-nitrogen bond in this

aminomethylation process makes the Mannich reaction an extremely useful synthetic

transformation and it can be illustrated in the following scheme.

General Scheme of Mannich Reaction

One - step binding of different molecules

R H + CH2O + HN -HoO

R

H2

/KM + CH20 + HN-(i) ^ /k<^^\. y® I R

Alternatives based on regioselectivity in polyfunctional substrates

R

hf^^V0 + CH2O+ HNH®.

®x/"-5*,0_«

Intramolecular reactions

H-A^—(B)—NH + CH2O R

Hence, the versatility of the Mannich reaction, along with the remarkable possibilities

of exploiting the reactivity of Mannich bases in providing further derivatives, makes it

possible to visualize and to readily realize the most varied chemical structures in conformity

with the model compoimds with the practical requirements and applications. The substrate

suitable for Mannich synthesis are widely available among a nimiber of different compounds,

and very few limitations are found in the choice of the amines, except for the unreactive

tertiary amine derivatives.

Mechanism

Since, it would hardly be feasible to give a detailed discussion of the mechanism

related to synthesis involving so many different classes of substrates, the main paths of the

Mannich reaction are considered in a general way as shovm below:

Mechanistic routes of the Mannich reaction

(X = OH, N<,...)

Depending on the nature of substrate, aldehyde and amine, pathway 'a' or 'b' is

followed and an unlikely trimolecular mechanism is also one of the possibilities (not shown

above).

Path-a: Initially formaldehyde reacts v^th the amine to give a condensation product

having the structure of x-aminomethyl derivative or methylimmonium salt, which is then

able to attack the substrate RH.

Path-b: A hyc^xymethyl derivative is generated, which gives the Mannich base by reaction

with the amine.

The main aspects concerning the reaction mechanism are

i) The relative importance of paths 'a' and 'b'

ii) The nature of the aminomethylating species in path 'a'

iii) The manner of attack by the reactive species on the substrate

Path 'a' is generally considered the preferred one when the amine is the most nucleophilic

species in the reaction medium. The presence of aminomethylating intermediates has been

observed by spectroscopic methods which favour the predominance of path 'a' over path 'b'.

On the other hand, some experimental results are in agreement v^th predominance of path

'b', they are due in particular to the tendency of a very large number of substrates to react

readily with aldehydes. Indeed, several successful Mannich bases have been synthesized

starting from the hydroxymethyl derivative.

7

Finally, some important studies of the influence of pH in the reaction between

formaldehyde and amine in biological systems, in the aminomethylation of polyacrylamide,

and in the use of aldehydes other than formaldehyde lead to the conclusion that under acidic

conditions, aldehyde attack on the amine is the rate determining step. Under neutral or basic

conditions the rate determining step is the hydroxyl elimination with the formation of cation.

Substrates

Usual substrates are, XH compounds having nucleophilic properties, with

X= C, N or other hetero atoms. In particular 'CH' compounds suitably activated by saturated

or unsaturated derivatives, 'NH' substrates are XH derivates having the 'H' atom bonded to

the hetero atom in the lower oxidation state; thiols, sulfinic acids, phosphines and phosphorus

acid derivatives. The Maimich reaction can also be carried out on unusual complex substrates,

such as hormones, antibiotics and alkaloids. The substrate with reactive prochiral centers,

gives rise to the possibility of chemo-, regio- and stereo selective products

A'', iV-dimethylacetamide (DMA), which has two methyl groups replacing the amine protons,

is used as a solvent. iV-methylacetamide is often used as the simplest model in studies of the

peptide bond. This is particularly important as acetamide has an amide bond, similar to the

essential bond between amino acids in proteins. Stavrovskaya' and Drusvyat-skaya

synthesized Marmich bases, iV-diethylaminomethyl-phenoxyacetamide and

A'-piperidinomethyl-m-toluamide show the greatest repellent activity. A series of Mannich

bases with chloro- and nitro-substituted benzamide were synthesized by the Marmich reaction

of substituted chlorobenzamide with various sulphonamides and secondary amines' " .

Andreas Brunschweiger and Dieter Heber ^ synthesized 2-bis-(dimethylaminomethyl)

acetamides by the reaction of iV-mono substituted acetamides with dimethyl(methylene)

ammonium chloride in the presence of phosphorus oxychloride using diethyl ether as a

solvent. Alexia Serafimidou et al prepared an acetamide derivative which bears two terminal

imidazole rings. This biomimetic ligand, A'-[2-(l^-imidazol-4-yl)-ethyl]-2-({[2-(l//-

imidazol-4-yl)-ethylcarbamoyl]-methyl}-amino)-acetamide, has been grafted on silica surface

via covalent bond. Dyimiaev and Lokhov ' studied the protonation equilibria of 2-amino-iV-

(2-oxo-2-(2-(pyridin-2-yl)ethylamino)ethyl)acetamide and the complexation of this ligand

with Cu(II) Ca(II), Zn(II) and Ni(II) °' ^ by glass electrode potentiometry and UV-Visible

spectrophotometry. The new amide-based ligand derived from biphenyl, iV-benzyl-2-{2'-

[(benzyl-methyl-carbamoyl)-methoxy]-biphenyl-2-yloxy}-iV-methyl-acetamide was

synthesized. Solid complexes of lanthanide picrates with this new ligand were prepared and

8

characterized. Gol'tsova^^ et al have prepared a series of novel benzofuran analogues of

iV; A^-di-n-(hexyl-2-phenylindole-3-acetamide), a potent and highly specific mitochondrial DBI

receptor complex ligand, by a modified Fischer method and found in vitro and in vivo to be

equally potent and selective as anti tumour drug.

Amines

Amine must have at least one reactive hydrogen atom and so includes NH3, N2H4 or

NH2OH derivatives and much more firequently, aliphatic as well as aromatic primary and

secondary amines. Hetero aromatic 'NH' derivatives are also employed. A huge number of

amines have been used in Maiuiich synthesis for specific purposes. The criteria and the

relevant features for selecting the amine to perform the Mannich reaction are the steric

hindrance and the basicity of amine. The use of polyfunctional amines leads to imdesired

by-products. Similarly, the use of bifunctional amines such as piperazine always leads to a

bis-Mannich base. Many insoluble alkaloids (e.g. quinine and atropine) are used medicinally

in the form of soluble salts. If alkali (sodium hydroxide) is added to solutions of such salts the

free amine is liberated. Short chain alkyl amines are used as raw materials of solvent, alkyl

alkanolamines, and ingredients of rocket fuels. They are used to make other organic

chemicals including rubber vulcanization accelerators, pesticides, quaternary ammonium

compounds, ' photographic chemicals, corrosion inhibitors, explosives, dyes and

pharmaceuticals. They are used in rayon and nylon industry to improve the tensile strength.

Garrett and Weber ^ produced the bis-ketonic Mannich base, N, N-his

(P-benzoylethyl)methylamine hydrochloride. The cytotoxicity of l-morpholino/piperidino-5-

nitroindole-2,3-dione-3-thiosemicarbazones was evaluated against the full panel of 60 human

cell lines in vitro screen " . The most active compound was foimd to be 1-morpholino

methyl-5-nitroindole-2,3-dione-3-A^-(chlorophenyl)tliiosemicarbozone and has the most

marked effects on a lung cancer cell line and on leukemia cell lines. The moipholine

derivative of 3-methyl-2-{[(morpholine-4-carbothioylimino)phenylmethyl] amino}-butyric

acid and their Ni", Cu" and Pt" complexes showed antifungal activity^° against the plant

pathogenic fungi Collectotrichumfragariae, Rhizoctonia solani and Phomabetae.

Ethosuximide, a derivative of pyrrolidin-2,5-dione, belong to a group of old

antiepileptic drugs and is still used in the treatment of epilepsy^ A great number of

3-phenylpyrrolidine-2,5-dione derivatives with pyridyl-, aryl- and aminophenyl-moiety at the

nitrogen atom, as well as 3-arylpyrrolidine-2,5-dione containing a 4-arylpiperazinyl-l-yl-

alkyl moiety at the nitrogen atom and 2-aza-spiro[4,4] nonane-l,3-dione have been

investigated by Flessel, Furst and Radding^ . Derivatives, of 3-arylpyrrolidine-2,5-dione was

synthesized and characterized. The studies in this group of pyrrolidin-2,5-dione derivatives

have led to a required for anticonvulsant activity^^ an aromatic ring at the 3-position of

pyrrolidine-2,5-dione moiety and a 4-arylpiperazine fragment with selected substituents at

the phenyl ring.

Aldehydes

Formaldehyde is usually employed in Maimich aminomethylation and it makes

possible to connect substrate and amine moieties through a methylene group. Commercial

formaldehyde exists in three forms, all of them are in polymeric association, which readily

produce the reagent molecule CH2O. In aqueous formaldehyde or formalin the quality of

molecules in the monomeric state is less than 27%, the remainder consisting of oligomers

having a polymerization degree below '10'. Trioxymethylene or 1,3,5-trioxane is a solid

cyclic trimer easily decomposed to formaldehyde by aqueous acid as well as by heating in

organic solvent. Paraformaldehyde is a crystalline linear polymer with a polymerization

degree '50' which becomes water soluble after depolymerisation on heating. Under some

conditions, formaldehyde is replaced in Mannich synthesis by methylene dihalogenides

CH2XY (X or Y= Cr, I") or by ether derivatives such as chloromethyl ether. Aminoalkylation

with aldehydes other than formaldehyde or even ketones has been successfully carried out.

Mannich bases of formaldehyde and benzaldehyde have been investigated extensively.

Cardeilhac '* generated an acyclic oxyimminium. ion, from secondary hydroxylamines

(2-methylfiaran, pyrrole or indole), formaldehyde in the presence of acetic acid. Hamers and

Casterman^^ isolated isatin and its derivatives have been reacted witli 4-(4'-chlorophenyl)-6-

(4"-methyl phenyl)-2-aminopyrimidine to form SchiflF bases and the iV-Mannich bases of

these compounds were synthesized by reacting them with formaldehyde and several

secondary amines.

Abbort ^ and coworkers developed a water-soluble prodrug of

doxorubicin-formaldehyde conjugate, a labile, active metabolite of doxorubicin. The lead

compoundisthedoxorubicin-salicylamideiV-Mannichbase, A^-(2-hydroxybenzamidomethyl)-

doxorubicin (doxsaliform), prepared by the action of salicylamide with doxorubicin in the

presence of formaldehyde. l-(Piperidinomethyl)-2-pyrrolidone was prepared by refluxing the

mixture of pyrrolidone, formaldehyde, and piperidine and also prepared a new compound

l-(Morpolinomethyl)-2-pyrrolidone by mixing of 2-pyrrolidone, formaldehyde and

morpholine. They yielded 97% of compoxmds. Hatzelmann^^ synthesized a series of

10

2,3-dihydro-2-oxo-l,3-disubstituted indoles by the reaction of 2,3-dihydro-2-oxo-3-

substituted indoles with 2-[(2,6-dichlorophenyl)amino]phenyl acetic acid in the presence of

formaldehyde. The newly synthesized compounds were characterized on the basis of

elemental analysis, IR, 'H N M R and mass spectra and studied immuno-modulatory properties

of the compound.

A set of new Mannich bases were synthesized, by reacting pyrazinamide (PAZ),

formaldehyde, and various substituted piperazines using microwave irradiation with the yield

ranging from 46% to 86%. Carbonnelle'' et al obtained Mannich bases by aminoalkylation of

3H-pyrrolo[3,2-fluro]quinoline and found to be potential vasorelaxing agents. To estimate

their vascular activity, prototypes l-(A';A -dimethylaminomethyl)-) and 4-(phenyl-piperazin-l-

ylmethyl)-3H-pyrrolo,[3,2-fluro]quinoline derivatives were studied in rat-tail arteries .

Mannich bases of benzamide derivatives of acetophenones have been disclosed to have

antitumour and cytotoxic activities by Malik'"' and others. l-Phenyl-3-dimethylaminopropan-

1-one hydrochloride, and related acetamide and benazmide derivatives were synthesized as

mono Mannich bases derived from acetophenone. The biological activity of the compounds

was examined by cytotoxicity against mouse renal carcinoma (Renca) and transformed human

T-lymphocyte (Jurkat) cell lines'*'"'* .

Raman'* et al synthesized a new Mannich base, A^-(l-morpholinobenzyl)semicarbazide

(MBS), formed by the condensation of morpholine, semicarbazide and benzaldehyde.

Coordination Tendencies of Acetamide, Acrylamide and Benzamide

The chemistry of coordination compounds of amides has aroused considerable interest

in view of their growing industrial and biological importance. They have been widely used for

many years in a variety of industries including the manufacture of cosmetics, textiles, leather,

paper, explosives, insecticides and plastics.

Acetamide, acrylamide and feenzamide possess;: an amino nitrogen and carbonyl

oxygen as the potential donor atoms. Substituted acetamides, acrylamides and benzamides

were considered versatile ligands due to their significant coordinating tendencies with metal

as well as non-metal ions. It is well known that they have received increased attention because

of multifarious ligating tendencies out of their ambidentate nature which sometimes leads to

novel structures. They can be monodentate, bidentate or bridging bidentate through any one

or two of the potential donor atoms N and O.

X-ray and neutron diffraction studies have shown that the molecules are in the keto form

with amino group in the same plane as that of the carbon atoms"* " .

11

R=CH3iCH2—CH & CgHg

The resonance structures weaken the C=0 bond and stiffens the C-N bond and so 6NH

mode is very weak. Due to the major contribution of dipolar resonance forms to structure, the

carbonyl stretching band found at lower frequency than those of the ketones. The carbonyl

stretching mode is not pure but mixed with NH2 bending modes. The coordination to the

metal in a complex is through N atom of NH2 group, there should be an increased electron

density on N atom and therefore the contribution of polar structure will be less. Hence N

coordination of acetamide/acrylamide/benzamide will be reflected by an increase in Vco, a

decrease in VCN and a decrease in VNH and 6NH. On the other hand, if the coordination takes

place through O atom, the contribution of polar forms will become more important and vc=o

decreases and VCN increases, VNH will undergo some changes even though the N atom is not

coordinating due to the hydrogen bonding interactions with the anions of metal salts.

The vibrational spectra of acetamide, acrylamide and benzamide complexes

reveals that the carbonyl stretching band (amidel) at 1665, 1672 and 1661 cm'' undergoes

bathochromic shift by about 10-20 cm''upon coordination through oxygen atom. The

amidell band at 1626, 1614 and 1618 cm'' attributed to the mixed (C-N) stretching and

(N-H) in-plane bending modes, also shifts to lower frequency.

The bands at 3350, 3360 & 3369 and 3180, 3183 & 3177 cm'' due to (N-H)

symmetrical and asymmetrical stretching will appear at higher frequencies. By contrast, the

coordination through nitrogen decreases (N-H) stretching frequencies and increases the

amidell band frequency. The imidate anion (RCONH') coordinates to metal ions via

nitrogen vidth lowering in the absorption frequency of amidel band and records an additional

band around 1480,1460 and 1450 cm''.

1.3 Metal Complexes of Acetamide and Related Derivatives

Anhydrous complexes or adducts of acetamide have been prepared in inert solvents

medium such as benzene, acetone or carbon tetrachloride, Acetamide forms 1:1 adducts with

boron tribromide and trichloride. Tellurium tetrachloride and acetamide forms a 1:2 adduct in

boiling benzene. The infrared spectrum suggests oxygen coordination of acetamide and five

coordinate tellurium'* " ^'. The band at 240 cm'' in the far IR region is cited as the diagnostic

(Te-0) stretching band. Paul and Dev have prepared a 1:1 (AlCl3:acetamide) complex in

12

nitrobenzene and a 1:6 complex in benzene. Silicon tetrachloride forms 1:4 (cream colour)

and 1:8 (light yellow) complexes with acetamide. In each case, IR spectrum has shown

oxygen coordination of acetamide.

Sul^air trioxide forms 1:1 (brown) and 1:2 (lemon yellow) complexes with

acetamide. The IR bands of the former complex at 3410 cm"' of V(N-H)5

1600 cm'' of 6(N-H)5 1380 cm"' of V(C-H) and 1105 cm"' have been considered to indicate

bonding via carbonyl oxygen. Sul| ;iur monochloride combines with acetamide to give the

acetimidate product (MeC0NH)2S which is soluble in water. It has been characterized by

mass and vibrational spectra. Tin(n) chloride is reported to form a four-coordinate 1:2

complex, while a probably six-coordinate diacetamide complex with tin(IV) chloride has been

reported by several groups. Acetamide complexes with tin(IV) bromide and diphenyltin(IV)

chloride and bromide have also been reported^ . In each case, the infrared spectrum indicates

acetamide oxygen coordination.

Much information on the interaction of alkaline earth cations with acetamide has been

inferred from studies in aqueous solutions mainly by phase diagram investigations, electrical

conductivity, DTA and TG studies " . Naturally the compounds claimed with compositions

BeCl2.3L.2H2O, MgCl2.2L, MgCl2.4L, MgBr2.6L, Mg(N03)2.4L.H20, Mg(N03)2.6L.2H20,

CaCl2.4L, CaCl2.2L.2H2O, BaCl2.6L and 2BaCl2.L have usually been acetamide hydrate

complexes as well as anhydrous ones with the proportion of acetamide in the complex

increasing with the concentrations of acetamide in the aqueous solution. The metal ion is

bonded via acetamide oxygen according to infrared spectral data of the complexes^^^ ''.

Thallium trichloride forms 1:1 and 1:2 complexes with acetamide. The latter, on the

basis of infrared, molecular weight and conductivity measurement, is shown to be dimeric

with chloro bridges between the six-coordinate thalliimi. The former complex is suggested to

be present as tefrahedral ions i.e. [TlCl2.2L]' and [TlCLt]'. Gobillon and Piret have reported

the formation of NaBr.2L (m.p. 144°C), NaI.2L (m.p. IIO^C) and KI.6L (m.p. 55°C) on the

basis of phase diagram and crystallographic studies^ .

Transition Metal-Acetamide Complexes

Formation of light green anhydrous copper(II) complex with composition

Cu(MeCONH2)2Cl2 from alcoholic solution has been claimed by Miodragovic et al ' ^ . The

decomposition temperature of 110°C.and magnetic moment value of 2.07 B.M. for the

complex are reported. The infrared spectrum indicates oxygen coordination. Copper(II)

bromide under similar conditions forms a complex with stoichiometry CuBr2.4L.2H2O.

13

Acetamide forms a light blue complex with copper(II) sul^^e having 1:1.5 stoichiometry.

Thermal data of the complex revealed its decomposition in the range of 210-240° resulting in

the formation of a 1:0.5 complex and lost all the acetamide moiety at 245-260°.

A blue coloured solid [Ni(MeCONH2)6]Cl2 complex has been prepared by refluxing

components in benzene. The preparation of light green [Ni.6L](BF4)2 complex has been

reported^^" \ The magnetic moment value (3.49 B.M.) and the infrared spectra reveal that the

Ni" ions in these complexes are octahedrally coordinated through oxygen of acetamides. An

octahedral [Ni(CNS)2,4L] complex has been characterized whose virational spectrum

indicates bonding via acetamide oxygen and thiocyanate nitrogen to the nickel(II) ion.

A number of zinc(II) complexes with acetamide have been prepared.

Sheldrick et al. have prepared ZnBr2 complexes with stoichiometrics ZnBr2.2L and ZnBr2.3L

which are distinguished by their melting points 59°C and 46°C respectively. The spectral and

crystallographic studies of the latter compound show dimeric structure with orthorhombic

geometry. By refluxuig acetamide with zinc(II) chloride in an inert solvent, a glassy solid

complex with composition [ZnCl2.2L] was obtained whose vibrational spectrum in the far IR

region suggested M-0 bonding through acetamide oxygen. Two types of the hydrated

complexes with composition Zn(N03)2.nL.2H20 (n= 4,6) have been reported* ' .

X-ray study^ of anhydrous [CdCl2.2L] complex has revealed monoclinic prismatic

structure. The complex has square planar geometry with carbonyl oxygen coordination. An

anhydrous 1:6 complex forming triclinic crystals as well as a 1:6 hydrate

[Cd(N03)2.6MeCONH2.2H20] (m.p. 82-9 rC) have been reported from phase diagram

studies of the ternary system.

The cobalt(II) complexes of acetamide with composition C0X2.6L (X= CI", NO3",

ClOO were prepared in non-aqueous media and characterized as the octahedral species by

infrared, reflectance spectra and X-ray diffraction^ ' ^ studies, which indicated the

coordination of acetamide through oxygen atom. Lee, Yang and Parr ^ prepared a cobalt

complex, of acetamide with composition [CoL2Cl]Cl and suggested tetrahedral geometry for

the compoimd.

Phase diagram studies on aqueous acetamide solutions have indicated the formation

of a number of complexes with manganese(II) haUdes of the types [MnCl2.2L.2H2O],

[MnX2.4LH20] (X= CI', Br") and [Mnl2.4L]. The study reveals octahedral stereochemistry of

the complexes'* ''' Manganese(II) nitrate forms an anhydrous 1:6 complex in acetone and the

14

hydrated complexes of the type Mn(N03)2.nL.2H20 (n= 4,6) in benzene under different

condition. The conductivity measurement shows the electrolytic nature of the compounds.

Mercury(II) halides form complexes [Hg.6L]Cl2 and [HgBr2.4L] with acetamide in

benzene or CCI4 solution. The complexes were characterized'^''^ by infrared and X-ray

diffraction studies and shown to be octahedral with oxygen coordination. Magnetochemical

and spectroscopic studies of acetamide complexes [MX2.4L] (M= Mn", Co", Ni";

X= Cr, Br", I") have indicated octahedral environment''*"' of the coordinated ligands in which

acetamide is bonded to metal ions via the carbonyl oxygen.

Chromium(III) perchlorate forms a 1:6 complex vdth acetamide. The ligand field

spectrum of the complex in nitrobenzene exhibits absorption bands at 16450 and 22940 cm"'

attributed to '*A2g—>''T2g(F) and ''A2g- ''Tig(F) transitions respectively. The complex is

considered to have an octahedral structure with oxygen coordination of acetamide""^^ The

spectral parameters reveals that the ligand field of acetamide is slightly less than that of water

but greater than those of urea or DMSO. The Dq values for these four ligands are 1645,1740,

1600 and 1577 cm"' respectively.

The complexes of uranylacetamide of the type [U02(02CR)2nL]

(L= acetamide, R= H, CH3", C2H5" & n=l, 1.5, 2 etc.) are reported. In the complex

[U02(02CH)2.2L] one of the HCO2" is monodentate while the other is bidentate. The U02^

ion is five coordinated as revealed by spectral study. The X-ray study of [U02(OAC)2.L]

complex indicates dimeric structure and each U02^ ion is in pentagonal bipyramid

structure^^"^^

Acetamide complexes of polyiodo iodates of Mn", Fe", Co" and Ni" ions having

composition [ML4]l2.4l2 have been characterized as ionic compounds. The presence of l5"ion

in the complexes is established. The vibrational spectra point to the coordination of acetamide

through the oxygen. The acetamide complexes of the type [M.4L.2H2O] I2 (M= Mn", Fe",

Co", Ni") were studied by infrared^ , Raman spectra and X-ray diffraction which revealed a

monoclinic structure. The metal ions are coordinated through acetamide oxygens with water

molecules in axial position. The complexes of MX2 (M= Mn", Ni", Co"; X= CI", Br", I') with

acetamide in aqueous solution have been studied by R\ikk et al. The complexes with

compositions MX2.mL.nH2O (m= 4, 6; n= 2, 4) and MX2.6L were prepared imder various

conditions. The complex [C0I2.4L] is reported to exhibit antitumour activity '"^ .

15

Symmetry group analysis of the acetamide complex [UO2SO4.L.2H2O] and

[UO2SO4.2L.H2O] has established the pentagonal bipyramid structure of the complexes. The

vibrational spectra have indicated the carbonyl oxygen coordination and the bidentate

chelation of the sulphate ion. The cis- and trans-isomers of the complexes have been

identified by the spectral investigation '' ^.

Complexes of Substituted Acetamides

The reduction in the rotation barrier of -NMe2 group in iy^A -dimethylacetamide as a

function of the concentration of cobalt(II) or nickel(II) perchlorate hexa-solvate has been

measured by NMR spectroscopy. Rotation enthalpy data have confirmed the infrared spectral

evidence that the coordinating atom is O rather than N. The paramagnetic complex

[C0CI2.2L] (L= CH3CONMe2) prepared ' '* from anhydrous cobalt chloride and

A .iV-dimethylacetamide, crystallizes in the orthorhombic space group. The complex is

considered to have a pseudo-tetrahedral structure and the amide ligand is bonded via oxygen

as revealed from infrared and electronic spectral data.

The complexes with composition M(pdg)zXpdg=N-(2-pyridylmethyl)-2-(dimethyl

amino)acetamide; M= Pt", Pd", Ni", Cu": X= Cr, Bf, NCO", NCS", C104' have been

characterized^ ' ^ by magnetic measurement, infrared, electronic and NMR studies. The

tetradentate ligand coordinates through the deprotonated amide N, pyridine N and amino N

atoms. The Pt'', Pd" and Ni" complexes are diamagnetic and suggested to exhibit square

planar geometry. The tefragonally distorted octahedral geometry is proposed for Cu"

complexes.

The complexes of iV-(2-pyridyl)acetamide vvith composition [ML2X2] (M= Co", Ni",

Cu"; X= cr, Br", NCS', NOs') have been prepared and characterized * ^ by magnetic,

infrared, electronic and NMR specfral studies. In the octahedral complexes the bidentate

ligand is chelated through pyridine N and amide O atoms. In the square planar complexes

[PdL2X2] (X= cr , Br') the coordination of the ligand is through pyridine N alone. In alkaline

medium, the ligand forms [PdL2].4H20 complex in which it acts as an anionic bidentate

ligand chelating through pyridine N and amide O atoms.

The complexes of 3-acetamidopyridine of the type [ML2X2](M= Cu", Ni", Co",

X= cr, Br') have been reported^^^^ ''. The infrared spectrum of Cu" complex indicates the

bonding of the ligand via pyridyl N and carbonyl O atoms. Reflectance spectra of Cu"

complexes have shown absorption maxima at 14,400 cm"'. The EPR spectra suggest

16

orthorhombic distortion. In the case of other complexes, the reflectance spectra exhibit three

main bands which suggest octahedral geometry °°' ° .

Physico-chemical properties of dimethyl-acetamide complexes MCl2.2L.nH2O

(L- AcNMes; M= Mn", Ni"; n= 6 and M= Co", n= 4), [M'ChL] (M' = Cd", Cu", Hg"),

[3CuCl2.2L] and [ZnCb.lL] have been studied'"^''" by electronic, infrared and conductivity

measurements. [M'C^.L] complexes are shown to be dimeric v^th two chloro bridges. The

complex [3CuCl2.2L] is shown to be a linear polymer with chloro bridges between copper

atoms.

Some amide complexes of uranium, tetrabromide formulated as [UBr4 L "] X= 3,

L= C2H5CON(C2H5)2; X= 2, L= C2H5CON(CH3)2; X= 2, L= C2H5CON(isopropyl)2,

(CH3)2CHCON(isopropyl)2 were prepared and characterized by infrared, near-mfrared, visible

spectra and their stereochemistries were discussed ' in terms of the steric crowding about

the central metal atom. Stereospecific linear NSNN tetradentate ligands

A^-[2-pyridylmethyl]-2-[(2-aminoethyl)thio]acetamide (PygeH) forms complexes of the type

[Cu(Pyge)X] (X= Br', Na', NCO', NCS", NO2"). The electronic, EPR and magnetic moment

data indicate square pyramidal structure. The terminal (NH2) group is present in the epical

position.

FT-lR and laser Raman spectra of p-nitroacetanilide have been investigated and the

bands are assigned assuming Ce point group for the molecule. The bands at 3010 and

1560 cm'' have been assigned to Fermi resonance of V(N-H) and the overtone of amidell band

of the amide group respectively. Its comparison with p-bromo and p-aminoacetanilide is also

reported"^''^^

A few lanthanide complexes of 2-acetylaniinothiazoles of the type [LnL2Cl2]Cl

(Ln= La"', Pr"', Nd"', Sm"', Eu"', Gd"', Tb"', Dy"') were prepared and characterized. The

infrared spectrum of 2-acetylaminothiazole exhibits bands at 3414, 1685, 1570, 1500 and

659 cm'' due to V(N-H) asymmetric, (C-0) stretching, amidell and (C-S) stretching modes

respectively. The (C-0) stretching and the ring skeletal vibrational modes show bathochromic

shift upon coordination of the ligand which suggests bonding of carbonyl oxygen and ring

nitrogen to metal ions. The complexs are shown to be diamagnetic having six

coordination' '*'' .

Bombardieri et al identified uranyl complex with composition [U02.L5].Bi2Hi2

(L= dimethylacetamide, diethylacetamide) in which the ligand was found to be coordinated 1 OH

through carbonyl oxygen .

17

Diacetamide forms chelates of the stoichiometries [CuX2.2L]pC= CI", NOs");

[MnX2.2L] (X= Cr, NCS'); [Mii(N03)2.2L]2H20; [MX2.2L]2H20 (M= Ni", Co"; X= Cr, Br")

[M(NCS)2.2L] (M= Ni", Co") and [Col2.2L]3H20. The infrared and thermal studies indicate

the involvement of both oxygen's of the ligand in bonding to metal ions. Thiocyanate is N

bonded. The nitrates are found to be outer-sphere complexes'^^"^'''.

The complexes of Th'^ and U^' A/-thiocyanates with iV^A '-diphenylacetamide,

A'iA^-dimethylacetamide and i\^,iV-dicyclohexylacetamide with composition M(NCS)4Lx

(X= 3 or 4) have been characterized as the octahedral species ' . The infrared and

UV-Visible spectra indicate oxygen coordination of the ligands. The uranyl sulphate complex

UO2.SO4.2L with dimethylacetamide is studied by TG and DTA, IR and X-ray. The complex

is shown to be orthorhombic with the two ligands trans to each other. The sulphato group is

considered to be bridged tridentate ligand in this complex'^^.

The interpretation of infrared and Raman spectra of a-chloro-acetamide and three

deuterated analogs CH2CICOND2, CD2CICONH2 and CD2CICOND2 in the crystalline state*^^

has been done on the basis of spectral comparison and the normal coordinate analysis.

Synthesis and characterization of dirhodium complex with asymmetric bridging acetamide

ligand such as [Rh2(CO)4(p,-L)2] (HL= MeC0NH2) have been reported. The complex was

prepared from [Rh2(|a,-Cl)2(CO)4] and MeCONH"(deprotonated by sodium hydride).

A series of indiimi derivatives'^^''"*" of iV-alkyl-B-mercaptoacetaniides having general

formula In(RNHC(0)CH2S)3 (R= C2H5, n-CsHy, I-C3H7, n-C4H9, I-C4H9) have been

characterized by IR, ' H and * C NMR and elemental analysis. The ligands are reported to be

coordinated through amide nitrogen and sulphur.

The complex of Rh"'ion v dth composition RhLs (L= 2-(acetylaminobenzoicacid))

has been identified as the octahedral species having coordination through nitrogen of the

amide group ahd oxygen of the carboxylate group of the ligand''*''''*^. Mononuclear zinc

complexes of a family of pyridylmethylamide ligands abbreviated as HL, HL''*', HL'^^'',

HL' ' '^ , and MeL^^'[HL = iV-(2-pyridylmethyl)acetamide; HL' ' ' '= 2-phenyl-iV-(2-

pyridylmethyl)acetamide; HL^^^ = 2,2-dimethyl-A^-(2-pyridylmethyl)propionamide;

HL™ = 2,2,2-triphenyl-A^-(2-pyridylmethyl)acetamide; MeL ' ^ = iV-methyl-2-methylsulfanyl

-7V-pyridin-2-ylmethyl-acetamide] were synthesized'''^''''' and characterized spectroscopically

and by single crystal X-ray structural analysis. The reaction of zinc(II) salts with the HL

ligands yielded complexes [Zn(HL)2(OTf)2], [Zn(HL)2(H20)](C104)2,

[Zn(HL''''^)2(H20)](C104)2, [Zn(HL'''')Cl2], [Zn(HL^'^)Cl2], and [Zn(MeL^^')Cl2]. The

18

complexes are either four-, five- or six-coordinate, encompassing a variety of geometries

including tetrahedral, square-pyramidal, trigonal-bipyramidal, and octahedral. The aromatic

thioether, 6-bis((2-(dimethylamino) ethylamino)methyl)phenyl) (tert-butyl)sulfane reacts with

[Pd(NCCH3)2Cl2] under S-C bond cleavage to give the dinuclearpalladiimi(II)complex

[L PdaCp.-Cl)] '*', where (L )~ = 2,6-bis((2-dimethylamino) ethylamino)methyl)-tliiophenolate.

All complexes were isolated as perchlorate salts and fully characterized by ESI-MS, IR, 'H

and ^ C NMR spectroscopy. The structures have been determined by X-ray crystallography.

The latter structure reveals a ni,3-bridging acetamidate unit showing that (L ) can alter its

conformation sufficiently to accommodate a multi-atom bridging species between the two Pd

atoms .

Anewamide-based ligand derived from biphenyl, Ar-benzyl-2-{2'-[(benzyl-methyl-

carbamoyl)-methoxy]-biphenyl-2-yloxy}-7V-methyl-acetamide was synthesized''* . Solid

complexes of lanthanide picrates with this new ligand were prepared and characterized by

elemental analysis, conductivity measurements, IR and electronic spectroscopies. The

molecular structure of [Eu(pic)3L] shows that the Eu(III) ion is nine-coordinated by four

oxygen atoms from the L and five from two bidentate and one unidentate picrates. All the

coordinated picrates and their adjacent equivalent picrates form intermolecular TC-TC stacking.

Furthermore, the [Eu(pic)3L] complex imits are linked by the n-n stacking to form a two-

dimensional (2-D) netlike supramolecule. Four cobalt(III) complexes containing the

polypyridine pentadentate ligands 7y;iV-bis(2-pyridylmethyl)amine-iV'-ethyl-2-pyridine-2-

carboxamide (PaPysH), N, Ar-bis(2-pyridylmethyl)amine-Ar'- [ 1 -(2-pyridylethyl)acetamide

(MePcPy3H), and A';iV-bis(2-pyridylmethyl)amine-A '-(2-pyridylmethyl)acetamide (PcPysH),

have been synthesized* •' ''. All three ligands bind the Co(III) center in the same fashion

with the exception of loss of conjugation between the carboxamide moiety and the pyridine

ring in the latter two.

The structures of [(PaPy3)Co(OH)][(PaPy3)Co(H20)](C104)3-3H20, [(PaPy3)Co(N02)]

(C104)-2MeCN, [(MePcPy3)Co(MeCN)](ClO4)2-0.5MeCN, and [(PcPy3)Co(Cl)]C104)-

2MeCN have been determined * '' . These ligands with strong-field carboxamido N donor

stabilize the +3 oxidation state of the Co center as demonstrated by the facile oxidation of the

corresponding Co(II) complexes (prepared in situ) by H2O2, [Fe(Cp)2](BF4), or nitric oxide

(NO). The Co-Namido bond distances of the compounds lie in the narrow range of

1.853-1.898 A. 'H NMR spectra of these complexes confirm the low-spin d* ground states of

the metal centers.

19

The Schiff base, non-symmetrical, compartmental ligand iV-[5-(2-{[2-hydroxy-3-

methoxy-phenyl-methylidene]-amino}-phenyl-sulfamoyl)-[l,3,4] thiadiazol-2-yl]-acetamide

(H3L) has been prepared^ ' ^ by condensation of the acetazol amide derivative 7V-[5-(2-

amino-phenylsulfamoyl)-[l,3,4]thiadiazol-2-yl]-acetamide2-hydroxy-3-methoxy-

benzaldehyde. The complexation of H3L with cobalt(II) chloride in pyridine under aerobic

conditions yielded [Co'"(HL)(py)2][Co"(py)Cl3]-CH3CH20H. The single crystal X-ray

structures of H3L are reported. In the mononuclear cation [Co"'(HL)(py)2]"^ the octahedral

cobalt(III) ion is bound at the iimer metal ion binding site and the larger empty outer metal

binding site is partly occupied by the hydrogen-bonded ethanol molecule of crystallisation.

Reaction of l,2-diaminoethane-iy,7V;iV,7V-tetra-(iV-methylacetamide), with K[AuCl4] in water

gave the complex [AuLCyCAuCLt] which when recrystallised from MeOH/H20 gave the

amidate-containing complex [Au(LH)Cl][AuCl4] the crystal structure of which shows LH to

be present as a tridentate ligand coordinated via its amino group nitrogens and a deprotonated

amide group. Two new N2S2 ligands [S-trityl-L-cysteine-acetamide-ethanethiolethylester

(Tr-L-CAATHa-Et) and S-trityl-D-penicillamine-acetamide-2-methyl-2-propanethiol)

ethylester (Tr-D-TMCAATH2-Et)] were prepared' "'' ^. These ligands, with the electron-

withdrawing carboxyl group separated by only two bonds from the NH amine group, belong

to monoamide-monoamine-dithiol (MAMA) class of chelates that typically form

M(VO)(N2S2) (M= Tc, Re) complexes with the ligand secondary amine and both syn and

anti isomers Re(VO)(N2S2) complexes were prepared ' '' ,

The reaction of 2,2-cis-[Rh2(Hacam)4(H20)2]C104 (Hacam= acetamide) with sodium

halides in aqueous solution gave crystals of [Rh2(Hacam)4X]n-H20 (X= CI", Br", I'). The

composition of the products depended on the reaction temperature. The anhydrous

compounds, [Rh2(Hacam)4X]n (X= CI', Br", T ; n = 2, 3, 4) were obtained at 40°C, and the

hydrated compounds, [Rh2(Hacam)4Cl]n-7nH20, [Rh2(Hacam)4Br]n-3nH20 and

[Rh2(Hacam)4l]n-2nH20 were obtained at room temperature (15-25°C). Reaction of

[Mo2(CH3CN)8](BF4)4 with the stoichiometric amount of acetamide leads to the violet,

moisture sensitive complex [Mo2(iJ.-CH3CONH) (CH3CN)6](BF4)3. Reaction of the latter

compound with two equivalents of dppm yields the purple [Mo2(n-CH3CONH)

(ja,-dppm)2(CH3CN)2](BF4)3. Three new hexadentate polyamine ligands (L), their acetate

bridged tetranuclear platinum complexes, [Pt4(ji-CH3COO)5(L)] ' (L^= 1,5,8,11,14,18-

hexaazaoctadecane, L = 1,11 -bis(2-pyridylmethyl)-1,4,8,11 -tetraazaundecane,

20

L = iV;iV-bis(((2-pyridyl-methyl)amino)ethyl)piperazine, and the same type of Pt4 complex

with L'* = l,10-bis(2-pyridylmethyl)-l,4,7,10-tetraazadecane) were prepared'^'"''".

The preparation and characterization of cis-P-[Co(gee)(gly)]"^ (geeH=A -{2-

[(2-aminoethyl)thio]ethyl}-2-aminoacetamide) and cis-P-[Co(ege)(AA)]"^ (egeH=iV-(2-aniino

ethyl)-2-[(2-aminoethyl)thio]acetamide; AA=gly, L-ala, L-leu, L-ile) complexes as PFe" or

mixed CF/PFe" salts are described"^'"^. H and ^ C NMR spectra of the new cobah

complexes demonstrate that only one geometrical isomer (with respect to the bidentate

chelate) is obtained with very high stereoselectivity. X-ray structural studies revealed that

orientation of the amino acidato chelate is the Pi configuration; that is, the isomer with the

carboxylate donor of the amino acid coordinated trans to the amido function to the

tetradentate backbone ligand. Pi-[Co(gee)(gly)]PF6-H20 crystallized in the monoclinic space

group P2i/a with a=11.748(2), b=11.810(2), c=12.341(3) A, p=101.43(2)° and Z=4 and was

refined to R=0.042. Pi-[Co(ege)(gly)]PF6 (II) crystallized in the monoclinic space group P2i/n

with a=l 1.467(2), b=8.173(l), c=17.421(3) A, p=106.69(2)° and Z=4 and was refmed to

R=0.052. The complexes, P-[Co(L)Cl2](L= gee or ege), were found to be convenient

precursors for the hydrolysis of the peptide bond of gly—gly to give Pi-[Co(L)(gly)]' under

mild conditions «.i77,i78_

The interaction of methazolamide(Hmacm) with Ni(II) ion and ammonia molecules

gives rise to the complex of formula [Ni(macm)2(NH3)4]. The complex crystallizes in the

monoclmic P2i/n space group with a= 14.255(4), b= 7.126(2), c= 12.444(3) A,

p= 113.12(3)° and Z= 2. The structure was refined to R= 0.065 (Rw = 0.065). The complex

consists of monomeric units which interact through hydrogen bonds and Van der Waals

contacts.

The Ni(II) ion is coordinated with the deprotonated sulfonamido nitrogen of the

(macm~) ligand in axial sites and the ammonia molecules in equatorial positions.

IR, electronic spectra and / H NMR results are also reported ' . The crystal structiare of the

neutral complex Pd(aap)2 of the title ligand shows a tetragonal Pd(II) with two trans ligands

each chelated by the ring nitrogen and amide oxygen. The amide nitrogen is deprotonated and

not coordinated. In the isomorphous M(aapH)2(N03)2 structures where M= Co(II), Ni(II), and

Zn(II), there are two axial water molecules and again two trans ligands chelated as above but

with a neutral amide nitrogen. For two of these complexes (M= Ni, Zn), the detailed

molecular structures were determined. These complexes possess an amide C-0 bond 0.04 A

shorter and an amide C-N bond 0.03 A longer than are foimd in the Pd(aap)2 complex.

21

Nickel(II), palladium(II), platiniim(II), and copper(II) complexes of

N-(2-pyridylmethyl)-2-(ethylthio)acetamide (ptgH) have been studied. In the diamagnetic

square-planar complexes [M(ptg)X]-nH20 (M= Pt, Pd, Ni) the amide group is coordinated

through its deprotonated N atom, tg being N,N,S-tridentate, while in the paramagnetic

six-coordinated nickel complexes Ni(ptgH)2X2-2H20 the amide group is coordinated through

its O atom, ptgH being N,0-bidentate. In the tetragonal copper complexes Cu(ptg)X-nH20

ptg acts similarly as in [M(ptg)X]-nH20, the axial positions being occupied weakly by H2O

molecules, whereas in the complexes Cu(ptgH)X2 the amide group exists in a rarely found

iminol form, ptgH being, N,N,S-tridentate. Only the complex Cu(ptg) C104-1/2H20 shows a

subnormal magnetic moment which may be due to copper-copper interaction through an

amide group .

A^-(2-pyridyl)acetamide (aapH) complexes of palladium(II), cobalt(II), mckel(II), and

copper(II) have been studied^ ^ by means of magnetic susceptibilities and mfrared, electronic

and PMR spectra. In the octahedral complexes M(aapH)2X2 (M = Co, Ni, Cu; X= CI', Br",

NCS', NO3"), bidentate aapH is chelated through the pyridine-N and amid-0 atoms, whereas

in the square-planar Pd(aapH)2X2 (X= CI", Br") unidentate aapH is coordinated through the

pyridine-N atom alone. Under alkaline conditions aapH is deprotonated m the presence of

palladium(II) to form Pd(aap)2-4H20, aap being an anionic bidentate ligand and chelating

through the pyridine-N and amide-0 atoms.

Twelve new thermally stable molecular adducts of the general formula

(C6H5)2SnX2-nL (X= CI", Br" or I"; N= 1 or 2 and L= acetamide, N-methylacetamide,

dimethylacetamide, diethylacetamide or diphenylacetamide) have been isolated in the

crystalline state and characterized' ' ^ . The infrared data on these penta or hexa

coordinated adducts indicate coordination from the oxygen atom of the Lewis base to the tin

atom. The 1:1 and 1:2 copper(II), nickel(n) and palladium(II) complexes of pyridine-2-

2,acetamide (abbreviation, paaH), a and P- C^CpaaH), CuBr2 (paaH), CuCl2(paaH)2,

CuBr2(paaH)2, Cu(C104)2(paaH)2, NiCl2(paaH)2-2H20, PdCl2(paaH)2 and PdBr2(paaH)2, were

prepared and their structure determined by magnetic moments, diffuse-reflectance and

infrared spectra ^ "' . The copper complexes have distorted octahedral or square-planar

structures, and the nickel complex an octahedral structure. In these complexes the ligand

coordinates to the metal ions through pyridine-N and amide-0 atoms. The palladium

complexes have square-planar structures with two unidentate paaH coordinating at the

position through pyridine-N atoms reacting Zn(CF3S03)2 with the title hgand (0-N) yields a

22

1:2 complex which precipitates from methanol as the [Zn(0-N)2(CH30H)2](CF3S03)2 salt.

The crystal structure of this complex (Pl/c, a= 13.711(2), b= 10.401(2), c= 16.358(2)A,

P= 124.27(1)°, R= 0.059, 1918 observed reflections) reveals the presence of a

centrosymmetric, nearly octahedral, complex cation' ' ^^ ' ''.

The all-trans configuration about Zn " is achieved by two methanol hydroxyl groups

and two bidentate ligands bonded via their pyridyl nitrogens and amide oxygens. The amide

group nitrogen is not coordinated to the metal, but it forms an N-H.. .0 hydrogen bond to the

CFsSO " counter ions. The influence of the amide substituent on the structure is discussed on

the basis of comparisons with the [Zn{N-(2-pyridyl) acetamide}2(H20)2] ^ ion containing a

similar amidopyridine chelate ring' '' ".

Some Applications of Acetamides and their Complexes

Acetamide and substituted acetamides have been vddely used for many years in a

variety of industries principally as a humectant, plasticizer, peroxide stabilizer and ingredient

of soldering fluxes. New uses of acetamide are being proposed, for example as a de-icing

agent. Molten acetamide is used as a non-aqueous solvent due to its low melting point, high

stability and less cost. Its dipolar nature makes it particularly a good solvent. Stafford

reported that over 400 organic compounds and over 200 inorganic compounds were dissolved

in molten acetamide. The earlier review and other publications noted the water like properties

of molten acetamide in physical properties, acid-base reactions and coordination. Acetamides

possess a wide spectrum of medicinal properties, including activity against cancer,

hypertension and inflammation'* .

Hahn et al' °'' Miscussed the cyclisation of A^-(4-methylquinolin-2-yl)acetamide. The

precursors iV-(4-methylquinolin-2-yl)acetamide derivatives were effectively prepared in a

single step from 2-aminoquinoline and naphthyridine derivatives continued to be of great

interest due to a wide spectrum of their biological activity. Antibiotics of this group are being

widely used for the diagnostics and chemotherapy of infectious diseases of humans including

AIDS. Some of new 1,8-naphthyridine derivatives including benzo[l,8]naphthyridine have

recently been patented as growth regulators, fungicides, bactericides, herbicides, insecticides,

and neumatocides of new generation, and they are also starting material for many

naphthyridine derivatives' '' '

The bacterial activity was exhibited by a series of l-[3-(4-benzotriazol-l/2-yl-3-fluoro-

phenyl)-2-oxo-oxazolidin-5-ylmethyl]-3-substituted acetamide derivatives against

mycobacterium' ^ species i.e M.tuberculosis, M.avium and M.intracellulare. The protection

23

by acetamide against Cu-mediated protein oxidation is through the chelation of Cu and the

formation of a redox-inactive ace-Cu complex. Acetamide also inhibited Cu'-catalysed

oxidation of ascorbate.

Molten acetamide solutions find wide applicability in electrodeposition of metals. They

provide high metal-cation concentrations with the absence of hydrolytic reactions .

Frequently acetamide-urea eutectics are used to achieve lower melting points

(mixture with 39 mol% iu*ea). Good quality deposits of metals could be obtained, even in the

presence of small quantities of water, by the electroreduction of metal solutions in molten

acetamide. The metal Zn, Cd, Pb, Sn, Co, Ni and Te have been extracted in pure form.

Reduction of Cr'^ and Cr'" compovmds and Ti^ chloride are reported' ^. Copper, iron and

nickel have been electrodeposited fi-om ammonium nitrate-acetamide-urea melts. Steels are

anodized in alkali metal nitrate-acetamide solutions.

Some platinum alkyleneacetamide complexes have been prepared and used as

anticarcinogenic agents. Omega-carboxypyrrolidinyl substituted arylacetamides were

synthesized by modifying the Raf kinase inhibitors to improve the aqueous solubility, an

important characteristic for oral drug' ' *' . The oral administration of the carcinogens

A-(2-fluorenyl)acetamide and V-hydroxy-2-fluorenylacetamide to male rats for 6 weeks

depressed the activity of liver catalase to the extent of 20-25 per cent.

Kallen^ ' prepared the Ru(III) metronidazole-maltolato and ethylmaltolato complexes,

trans-[RuL2(metro)2]CF3S03 (L= ma or etma) and tested for potential anti-tumour activity

against the human breast cancer cell line MDA-MB-435S using a so-called MTT assay in

phosphate-buffered saline; a= 3-hydroxy-2-methylpyran-4-onato, etma= 2-ethyl-3-hydroxy

pyran-4-onato, metro=2-methyl-5-nitro-1 H-imidazole-1 -ethanol(metronidazole);

MTT= 3-(4,5dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide.

The other potential application of acetamide solutions is in thermal batteries. Alkali metal

nitrate acetamide solutions are considered important for battery applications v^th iron and

cobalt electrodes. The solutions cause very little corrosion even to inexpensive steels. Such

batteries with lithium anodes give high discharge rates when combined with Ag' or Ce'^ salts

as cathodes. In lithium nitrate batteries even small amount of acetamide increases anodic

current densities significantly^ ' .

Eichhom et al synthesized various analogues of indolyl, naphthyl and phenylethyl

substituted thiazolyl, halopyridyl and benzothiazolyl acetamide as a new class of

24

anti-allergic agents and examined their in vitro effects of the high affinity IgE/FceRI

receptor mediated mast cell leukotriene release^" .

1.4. Metal Complexes of Acrylamide and Related Derivatives

To evaluate the health effects and risks associated with acrylamide exposure, it is

important to study the chemistry and biology of pure acrylamide and acrylamide-based

(metabolites) compounds. Metal ion coordination to acrylamide also enhances the

electrophilicity of acrylamide and increases its reactivity. Nickel-containing

2-pyridylanthracene, for example, which models the activity of metal containing enzymes that

are involved in the conversion of carboxyl amides to carboxylic ester or acids, is known to

catalyze the conversion of acrylamide to ethylacrylate. Alcoholysis of acrylamide with

methanol has also been reported in the presence of rare earth transition metal complexes " .

Acrylamide and few biologically relevant adducts of acrylamide with ethylenediamine,

cyclone and pyrazole are able to coordinate to biologically relevant metal ions.

The solution and soUd-state chemistry of acrylamide or acrylamide-based

ligands (metabolites) with less acidic biologically relevant metal ions are of great interest due

to the biological relevance of the amide group in peptides and proteins, their fimction as

models of metalloproteins active sites and their relevance in elucidating the mechanism of

acrylamide metabolism in biological systems and its health effects " . From the industrial

point of view metal complexes of acrylamide are employed in the production of water-soluble

polymers and copolymers that are used in many commercial and scientific applications.

The acrylamide metal complexes are generally monomeric in solutions of common

solvents, but a few are dimeric or polymeric compounds. Grigore and Vasilica' ' measured

the enthalphies of formation of O bonded acrylamide complexes of the type [M(Acry).Cl2]

(M= Mn, Fe, Co, Ni, Zn, Cd, Hg; Acry= acrylamide) and calculated the M-0 bond

dissociation energies and reported that the M-0 bond in these complexes are weaker than

M-N bond in the other similar octahedral complexes. The strength of M-0 bond also depends

on the nature of the metal.

Metal complexes of A -phenylacrylamide and iV.iV-diethylacrylamide with several

metals were reported. Octahedral, and mixed octahedral and tetrahedral complexes of Ni" and

Co" are of types [MLeJXj (M= Ni; X= Br", 1\ C104' and M= Co; X= Y, CIO4") and

NiL4(NCS)2. Blue coloured [NiLe] [NiCLj] isomerizes in the solid state into a

25

five-coordinated high spin red complex NiL3Cl2. Perchlorate complexes of

iV. ^diethylacrylamide such as [ML6](C104)2, (M= Mn, Co and Cu) and [CuL4](C104)2 and

1:2 adducts with Cu ^ were also isolated and characterized^ " ^ .

Bimetallic complexes of the formula M[Ag(SCN)(SeCN)]2.2L (M= Co", Ni",Cu";

L= acrylamide) and are rare earth metal nitrate and acetate complexes with acrylamide were

also reported^ " ' . A crystal and molecular structure study on the complex Cu" formate

monoacrylamide indicated the presence of both intra- and inter-molecular hydrogen bonding

as well as the bonding of acrylamide through oxygen to metal atom. Carbonyl oxygen

coordinated to metal was reported in the complexes of the formula M(NCS)2.2L (M= Zn",

Cd"), CoL4(N03)2, [CoL6](C104)3, NiCUX, CrL4X2 (X= CI', Br'), CrL2Cl2 (L= acrylamide).

Acrylamide exhibited both unidentate and bidentate behaviour in the same complex

C0L4(N03)2.

Ammonia, aliphatic amines, phosphines, chlorine, bromine, bisulfite, and

dithiocarbamates readily react with the vinylic double bond as to alkylation of proteins,

non-protein SH groups, and A'-terminal NH2 groups of the vanillin residue of haemoglobin

and NH2 of guanine and other nucleic acids, hence the reasons for concern in biological

systems^^". Reactions of the amide group include hydrolysis, dehydration, alcoholysis, and

condensations with aldehydes. Acrylamide is readily polymerized in the presence of free

radicals.

Coordination complexes of the type MX4.L and MX4.2L (M= Sn, Ti; X= CI', Br", I"

and L= N-allyl thiourea, acetylene urea. N-allylurea, N-allyl acrylamide and

N-allyl benzamide) have been prepared^^^ IR spectral results indicate coordination through

nitrogen in N-allyl thiourea and through oxygen in rest of the amides. The stability constant

(log K) values have been calculated fi-om the carbonyl stretching fi:equency of the complexes

and related to the magnitude of the shifts observed on coordination. .

A series of Zn and Cd complexes with N-methyl or phenyl and N,N-dimethyl or

diphenyl acrylamides (RNHCONHR'; where R= Me, Et, Ph and R - H) has been isolated and

studied. The structure of [CdCl2{(CH2=CH)CO(NHCH3)}2]n is a polymer chain built fi-om

[CdCl3CH=CH2] distorted octahedral, and the structure of

[CdCl2{(CH2=CH)CO(NHC6H5)}2] is monomeric with distorted tetrahedral geometry.

Anti-ferromagnetic linear polymers, CrCl2.2MA, its acetone adduct, CrCl2.2PA and

CrCl2.2DCA, and high spin magnetically dilute complexes CrBr4.4MA, Crl2.6PA, CrBr2.5PA,

Crl2.4PA, CrBr2.5DCA and Crl2.6DCA, where MA, PA and DCA are respectively

26

N-methylacrylamide, N-piperazinomethylacrylamide and N-dicyclohexylacrylamide were

synthesized and characterized ' .

Metal complexes of acrylamide are generally prepared by direct reaction of metal ions

with acrylamide or base-catalyzed hydrolysis of coordinated acrylonitrile,

M-N=C-CH=CH2]"" (where M""*' = Co"" ), The fust route usually gives complexes in which

the metal is coordinated through oxygen, although coordination through nitrogen or the olefin

has been reported^^^ in some cases. The second route usually forms a more stable

deprotonated N-amidate, [M-NHC(0)CH=CH2]^""' , which is protonated instantaneously in

acidic conditions to give N- or 0-coordinated complexes.

Faggiani et al ^ studied the effect of the thermally initiated frontal polymerization of

acrylamide complexes of transition metal nitrates such as those of Mn(II), Co(II), Ni(II) and

Zn(II) was disclosed. The rate of the polymerization front propagation was found to be

2-9x10" cm/c, depending appreciably on sample diameter and density, as well as the presence

of radical inhibitor additives. The rate was found to decrease in the series: Co(n) > Ni(II) >

Mn(II) > Zn(II). Polymerization was shown to occur directly in the melting region of a

complex at 80-100°C to give three-dimensional polymers. A mechanism of the

polymerization being initiated with the products of the partial nitrate group decomposition

was proposed.

Lippert^ ' synthesized the complexes of Co", Ni", Zn", Cd" and Hg" halide with

N,N-diphenylacrylamide and characterized them as [ML2X2] (X= CI", Br", I") complexes with

M-0 bonding.Co" complexes of the type [C0L2X2] (X= CI', Br", CIO4") with N,N-piperidino

methylacrylamide are reported. O bonded high spin octahedral complexes of Co" complexes

with benzylacrylamide (L) like [CoL2A2](A= methylacetoacetate, ethylacetoacetate) have

been prepared. The thermal decomposition of the complexes A1L6(N03)2, FeL6(N03)3 and

MnL4Cl2(L= acrylamide) have been studied in air and oxygen by simultaneous recording of

TG, DTG and DTA curves and the metal oxides formed by decomposition have been

identified by X-ray powder diffraction.

A theoretical study of proton-coupled electron transfer (PCET) in the radical anionic

thymine-acrylamide complex is presented. This study is based on a multi state continuum

theory, in which the solute is represented by a multi state valence bond model, the solvent is

described by a dielectric continuum, and the transferring hydrogen nucleus is represented by a Oil O 10

quantum mechanical wave function. The DNA-acrylamide system is highly sensitive to the solvation properties of the system.

27

The coordination chemistry of acrylamide, CH2=CHC(0)NH2 (also known as

2-propenamide,=AAm) with a variety of transition metals were studied by

Taquikhan^^* et al. Despite the potential versatility of acrylamide as a ligand, only few

complexes that coordinate exclusively through the carbonyl oxygen,

[Co(AAm)4(H20)2](N03)2, [Cu(AAm)4(N03)2], [Co(AAm)4Cl2] and [Co(AAm)6][CoCl4]

have been fully characterized by spectroscopic and X-ray diffraction studies.

Poly(2-acrylamidoglycolicacid-co-acrylamide), P(AGA-co-AAm) and poly(2-acryl 000 Oil

amidoglycolicacid-<7o-4-acryloylmorpholine), P(AGA-co-AMo), were synthesized by

radical polymerization. The water-soluble polymers containing tertiary amine, amide,

hydroxyl, and carboxylic acid groups were investigated as polychelatogen, in view of their

metal ion binding properties by using the liquid-phase polymer-based retention technique

under different experimental conditions. The retention properties for the following metal ions

were investigated: Ag"", Co^^ Ni^^ Cu "", Zn^^ Cd^^ Pb "", Al , Cr ^ and Fe "". P(AGA-co-

AMo) showed a selective retention for trivalent cation Al " at pH 3, but no retention at higher

pH. P(AGA-co-AAm) showed the highest metal ion retention capability, specially at pH-5

and pH-7 with values close to 100% to divalent cations.

Oxovanadium(IV)tliiocyanate complexes of the formula V02(NCS), with

p-chlorophenylacrylamide, p-bromophenylacrylamide and pyrrolidinomethylacrylamide, were

shown to be N bonded species. Ru'" complexes of phenyl-, naphthyl- and ditolyl-acrylamides

were characterized as O bonded in nature^ ' ^ '*'.

Acrylamide complexes of metal perchlorates and tetrafluoroborates,

[M(OC(NH2)CH=CH2)6][X]2 (M = Fe, Co, Ni, Zn; X = C104', BF4'), have been prepared and

characterized using single crystal X-ray diffraction, IR spectroscopy and elemental of

acrylamide ligands accompanied by the anions. The tetrafluoroborate or perchlorate counter

anions do not coordinate to the metal atoms or take part in strong secondary interactions such

as hydrogen bonds with coordinated ligands. Single crystal X-ray structures of these

complexes prove that the ligands are coordinated exclusively via the carbonyl oxygen atom.

Bonding through the nitrogen atom has not been observed in these complexes '''' ''*' '®.

New derivatives of 1-(furan-2-carbonyl)- and l-(furan-3-carbonyl)-3-phenyl-

substituted acrylamide have been synthesized. X-ray single crystal diffraction analyses of foui-

selected compounds, l-(fliran-3-carbonyl)-3-(2-trifluoromethylphenyl)acrylamide,

l-(2-methylfiiran-3-carbonyl)-3-(2-fluorometliylphenyl)]acrylamide,l-(2,6-dichloro phenyl)-

3-(2-methylfuran-3-carbbnyl)acrylamide and l-(4-methoxyphenyI)-3-(3-methyl-2-furan-

28

carbonyl)acrylamide, were studied '' ' '*. Transition metal complexes of the types [MLCI2]

(M= Co, Ni, Pd and Pt; L= 3-N-dibenzofurylacrylamide), [FeLaCb] and [(CuCl2)L2] were

prepared and characterized in which the ligand L acts as bidentate. Two series of coordination

complexes of CdCl2 and HgCh with 3-monosubstituted- and 3,3-disubstituted-l-furoyl

acrylamides were synthesized and characterized. These acrylamide ligands behave as neutral

ligands, which coordinate to the metal ions through the O atom of the amide group.

The new acrylamide iron(II)/iron(III) complex [Fe(0-QC(NH2)CH=CH2)6]

[Fe20Cl6] was obtained by the reaction of a mixture of anhydrous FeCl2 and anhydrous FeCla

with acrylainide (molar ratio 1:2:6) in 98% pure commercial nitromethane under nitrogen

atmosphere. According to an X-ray structural analysis, the acrylamide ligands are coordinated

via the amide-oxygen atoms. The formation of the (jj,-oxo)bis[trichloro ferrate(III)]' ~ anion

presumably resulted from partial hydrolysis of FeCls or [FeCLj]" by small amounts of water in

the nitromethane and/or by the nitromethane itself.

The molecular structure of copper(II) chloride complex with acrylamide

(AAm=CH2=CHCONH2), [Cu(AAm)4Cl2], was determined using X-ray diffraction

analysis ^ . The complex crystallizes in the cubic space group I-43d with

a = 17.8310(2) A, p = 90°, and V = 5669.27(11) A^ for Z= 12. The acrylamide molecules

bind to the metal center via the carbonyl oxygen atom (Cu-0 1.996 A). The coordination

geometry of the metal center in the complex involves a tetragonally distorted octahedral

structure with four 0-donor atoms of acrylamide bonded in the equatorial positions and two

chlorides in the apical positions.

The complexation of gadolinium (Gd " ion with poly(methacrylic acid) and its

copolymers was studied^^ . Poly(methacrylicacid-co-acrylamide) formed tlie

tris (carboxylate)-coordinate gadolinium complex with an extra large complex formation

constant, while poly(methacrylic acid) formed the biscoordinate complex. Transparent and

flexible film containing a high proportion of Gd ion was prepared by castmg the complex

solution of poly(methacrylic acid-co-methylacrylate). The complexed Gd ion was uniformly

dispersed in the film and showed paramagnetism.

The complexes SnX4.2AA (X= CI", Br'; AA= acrylamide), SnCL4.2AA-d2,

(AA-d2 = CH2CHCOND2) and SnX4.2DAA (DAA= TVJTV-dunethylacrylamide) have been

prepared and characterized^^^^^^ ''. Whereas the DAA complexes exhibit the normal O-

coordination, the AA compliexes appear to the first examples of A -coordmated amides. The

primary evidence for the different modes of bonding comes from mass spectral studies, with

29

photoelectron, infrared, and NMR spectroscopy providing supporting evidence.

Fragmentation patterns for SnCl4.2ADD and SnCl4.2AA show SnO" and Sn!<t, SnNH^ and

SnNH " peaks, respectively. Apparently anomalous data from infrared and NMR studies are

explained in terms of new resonance forms which contribute to the electronic structure

through N-coordination.

On the basis of low-frequency infrared studies, the AA complexes are assigned the cis,

and the DAA complexes the trans, configurations. An evaluation of the utilization of the

shifts upon the coordination of the infrared bands V(NH2), V(CO), 5(NH2) and V(CN)5 as a means of

determination of the mode of bonding of amides is presented

Simple molecular orbital calculations were carried out on acrylamide (AA) and

iV.A'-dimethylacrylamide (DAA), the results indicating that molecules of lower energy are

formed upon coordination through N rather than O. Protonation studies in FSO3H by NMR

show that both AA and DAA are N-protonated, in agreement with the M.O. calculations.

Complexes of some first row fransition metal perchlorates and tetraflouroborates exhibit

attachment through nitrogen for the AA but 0-coordination for the DAA molecules. Steric

factors are invoked to explain the different modes of bonding . Bemhard and Dietmar

synthesized series of 3-substituted4-[5-(4-methoxy-2-nitrophenyl)-2-furfurylidene]amino-5-

mercapto-1,2,4-triazoles.

Some Applications of Acrylamide and their Complexes

Most uses for high molecular weight polyacrylamide in water treatment, mineral

processing, and paper manufacture are based on the ability of these polymers to flocculate

small suspended particles by charge neutralization and bridging. Low molecular weight

polymers are employed as dispersants, crystal growth modifiers or selective mineral

depressants. In oil recovery, polyacrylamide adjusts the rheology of injected water so that the

polymer solution moves imiformly through the rock pores, sweeping the oil ahead of it. Other

applications such as super absorbents and soil modification rely on the very hydrophilic

character of polyacrylamide.

Six series of N-acyl-N-phenylacrylamides of piperidines, were synthesized and

several compounds were found to exhibit anti-inflammatory activity, a low level of

infiltration anesthesia in mice '' ^ ' '"'' '* . Transition metal complexes of substituted

aminophenylacrylamide have been screened as potential fungicides. The ion-exchange resin

2-hydroxyacetophenoneoximepolyacrylate-trioxane and its polychelates with bivalent

30

Mn, Co, Ni, Cu, Zn, VO, UO2 ions showed antimicrobial activities against P.fluorescenes,

A.niger, T.longibrachiatum and B.subtilis.

Acrylamide derivatives play an important role to exhibit anticorrosive activity.

Metylacrylamide as corrosion inhibitor for mild steel in acid solution have been

established ^ " ^ . The studies on the uihibition of corrosion of iron by acrylamide and its n-

substituted derivatives suggest that the aryl-iV-substituted acrylamide with the least

protonation and maximvim adsorption is a better inhibitor than acrylamide and

alkyl-A -substituted acrylamide.

Chiral acrylamide derivatives of several substituted halopyridyl and thiazolyl

compoimds were synthesized '* ' '' as non-nucleoside inhibitors of the reverse transcriptase

enzyme of human immune-deficiency virus (HIV-1). Molecular modeling studies indicated

that the R stereoigomers would fit the NNRTI binding pocket of the HIV-IRT much better

than the corresponding S stereoisomers.

A theoretical study of proton-coupled electron transfer (PCET) in the radical anionic

thymine-acrylamide complex is presented. The influence of neighboring DNA base pairs is

determined by studying solvated DNA-acrylamide models in addition to the solvated

thymine-acrylamide complex ' .

The potential versatility of acrylamide as a ligand, only few complexes that coordinate

exclusively through the carbonyl oxygen, [Co(AAm)4(H20)2](N03)2, [Cu(AAm)4(N03)2],

[Co(AAm)4Cl2], and [Co(AAm)6][CoCl4] have been fiilly characterized by spectroscopic and

X-ray diffraction studies. Finally, some reactions involving acrylamide or acrylamide-based

ligands coordinated with less acidic biologically relevant transition metals are considered in

order to form a notion of the potential role of such interactions in acrylamide reactivity in

biological systems^^°.

Udaisingh et aP^ synthesized and reported spectroscopic (IR, 'H and ' C NMR)

characterization of new complexes of Pt(II), Pd(II), Cu(II) and Hg(II) with the Schiff base

ligand MeCONHCH2CH2N=CHPy (Py = pyridine) are reported, together with studies on the

cytotoxicities of these complexes, and [ReBr(C0)3] against human leukemia (MOLT-4),

breast cancer (MCF-7) and Chang Liver (non-cancerous) cells. Novel benzofuran analogues

of 7V,iV-di-«-hexyl-2-phenylindole-3-acrylamide, a potent and highly specific mitochondrial

DBI receptor complex ligand, were synthesized by a modified Fischer method and foimd in

vitro and in vivo to be equally potent and selective antimicrobial agents ^ " ^ . The Schiff

31

bases of phenyl hydrazones of acrylamides by reacting acrylamide and the appropriate

aromatic primary amine/hydrazines were prepared^^''.

1.5 Metal Complexes of Benzamide and Related Derivatives

A series of A^-(2-pyridyl)benzamides and their nickel complexes,

[iV-(2-pyridyl)benzamide]dinickel(II)di-|j,-bromidedibromide and (aryl)[A^-(2-pyridyl)

benzamido](triphenylphosphine)nickel(II) were synthesized and characterized^^^. The single-

crystal X-ray analysis revealed binuclear nickel complexes bridged by bromine atoms and

each nickel atom adopts distorted trigonal bipyramidal geometry. The key feature of the

complexes has a six-membered nickel chelate ring including a deprotonated secondary

nitrogen atom and an 0-donor atom.

The nickel complexes show moderate to high catalytic activity for ethylene

oligomerization v^th methylaluminoxane (MAO) as cocatalyst. The activity of

iV-(2-pyridyl)benzamides/ MAO systems is up to 3.3 x 10'' g moF^ h~ whereas for

[iV-(2-pyridyl)benzamide]dinickel(II)di-n-bromide and (aryl)[A^-(2-pyridyl)benzamido]

(triphenylphosphine)nickel(II)/MAO systems it is up to 4.94 x 10^ g mol"' h~'.

New complexes of lanthanide nitrates With N-(2-pyridyl) benzamide (PyBA) of the

type [Ln(PyBA)2](N03)3 where Ln= La, Pr, Nd, Tb, Ho, Er, Yb and Y have been prepared

and characterized by analysis, conductance, infrared, carbon-13 NMR and electronic

spectral studies. The molar conductance and infrared data point to the coordinated nitrate

groups in the complexes. Infrared and carbon-13 NMR have been interpreted in terms of the

coordination of the ligand to the tripositive lanthanide ion, in a bidentate fashion, through the

oxygen of the benzamide group and the nitrogen of the pyridine ring.

A''-Phenylbenzamide-2,2'-dicarboxyHc acid (PBDA) and its copper(II), mckel(II),

cobalt(II), zinc(II) and manganese(II) chelates have been syntliesized and characterized^ '' ^^

by their physical measurements, infrared and electronic spectra and magnetic moment data.

The above compounds having composition [ML2]X2.4X2 have been characterized as ionic

compounds. The IR spectra point to the coordination of benzamide through the carbonyl

oxygen. The electronic spectra and magnetic data revealed that the complexes have octahedral

geometry.

Glibenclamide 1 - [4- [2-(chloro-2-methoxybenzamido)ethyl] -benzenesulphonyl] -3 -

cyclohexyl-urea,; 5-chloro-N-[2-[4[[[(cyclohexyl(amino)carbonyl]-amino]suIfonyi1-J3henyli'

32

ethyl]-2-methoxy benzamide or l-[[p-[-2-(5-chloro-o-anisamido)ethyl]phenyl]-sulphonyl-3-

cyclohexylurea, a sulphonyl urea derivative have been synthesized and characterized

A number of zinc(II) complexes with glibenclamide have been prepared.

Fiol et al have prepared ZnS04 complexes with stoichiometrics ZnS04.2L and ZnS04.3L

which are distinguished by their melting points 169°C and 184°C respectively. The spectral

and crystallographic studies of the latter compoimd show dimeric structure with orthorhombic

geometry. By refluxing glibenclamide with zinc(II) nitrate in an inert solvent, a solid complex

with composition [Zn(N03)2.2L] was obtained, the vibrational spectrum in the far IR region

suggested M-0 bonding through benzamide oxygen. Two types of the hydrated complexes

with composition ZnCl2.nL.2H2O (n= 4,6) have also been reported^ "' " .

Insoluble solid porous ethyl-2-iminobenzoate immobilized polysiloxane ligand system

of the general formula P-(CH2)3-NH(C6H4)COOC2H5, (where P represents [Si-0]n siloxane

network) has been prepared by the reaction of 3-iodopolysiloxane P-(CH2)3-I with ethyl-2-

aminobenzoate. The modified polysiloxane derivatives; imino(7V-2-aminoethyl)benzamide

P-(CH2)3-NH(C6H4)CONH(CH2)2NH2, and imino (iV-diethylenediamine)benzamide

P-(CH2)3-NH(C6H4)CONH(CH2)2NH(CH2)2NH2 ligand systems were prepared^^ ''' ' by the

reaction of ethyl-2-iminobenzoate ligand system with ethylenediamine and diethylenetriamine

respectively. The new modified polysiloxane ligand systems exhibit high potential for the

uptake of the metal ions (Mn "", Fe^ , Co^ , Ni "", Cu "" and Zn^^ with an efficiency of 92-98%

after recovery from its primary metal complexes. The seimmobilized-polysiloxane ligand

systems imdergo chemical degradation the level of which depends on pH.

The metal-mediated coupling between the nitriles RCN in the platinum(IV) complexes

trans-[PtCl4(RCN)2] (R=Me,Et,CH2Ph,Ph), cis/trans-[PtCl4(MeCN)(Me2SO)] and the newly

synthesized^ ' ^ bifimctional oximehydroxamic acid, viz. 7y;2-dihydroxy-5-(l-

hydroxyiminoethyl)benzamide, proceeds smoothly in CH2CI2 at 4(M5°C to accomplish the

new metallaligands HN=C(R)ONHC(=0)C6H3(2-OH)(5-C(Me)=NOH) with pendant oxime

functionalities due to the regioselective addition of the reagent via its hydroxamic groups. The

obtained iminoligands exist in hydroxamic/hydroxunic tautomeric equilibrium in solution.

The structures of the isolated compoxmds are based on elemental analyses (C, H, N), IR, ID

^H, ^^C{^H}, and 2D NMR correlation experiments, i.e. ^H, "C-COSY, 'H, ^^C long range

COSY, ^H, ' N-COSY, and 'H, '^N long range ^ ' ^ .

2-Benzoylimino-l,3-diaza-6,9-dioxacycloundecane was synthesized from iV-dichloro

methylene-benzamide and l,8-diamino-3,6-dioxaoctane using the dilution principle. The

33

crystal structure reveals again, besides an intramolecular N-H...0 hydrogen bridge, the

formation of molecular chains caused by one intermolecular N-H...0 hydrogen bridge per

molecule. The bulky structure of the l,3-diaza-6,9-dioxacycloimdecane ring seems to prevent

any complex formation of transition metal ions. New oxorhenium complexes with

2-(diphenylphosphanyl)-N-(2-thioethyl)benzamide (H2PNS) and trimethyl-, triethyl- and

triphenyl-hydroxyl silylated monodentate thiols are reported " . These new complexes

have been prepared by reacting [N"Bu4][Re(0)Cl4] with the tridentate H2PNS and the

corresponding silylated thiol at room temperature. The characterization of the complexes

involved elemental analysis, ' 'P and 'H N M R spectroscopies and X-ray crystallographic

analysis for the triethyl-silylated Re complex. The synthesis of the title ligands

A' benzothiazol-2-yl-benzamide, iV-benzoxazol-2-yl-benzamide and iV-(lH-benzimidazol-2-

yl)-benzamide is described. The molecular structure confirms the localization of a hydrogen

atom at the nitrogen atom of the benzamide group.

The reaction of N-(2-chloroethyl)benzamide with ArTe- Na+ generated in situ by

borohydride reduction of AraTea, has resulted ' ' ^^ in N-[2-(4-methoxyphenyltelluro)

ethyl]benzamide(L). The complexes having stoichiometrics [PdCl2(L)], [PtClaCL)],

[(Phen)Pd(L)](C104), [(DPPE)Pd(L)](C104), and [RuClaCL)] were synthesized and

characterized by elemental analyses, conductance and molecular weight measurements, NMR

('H and ' C) and FT-IR spectra.

The synthesis and characterizatioii of new dinuclear Mn'" and tetranuclear

Cu" complexes, [HL.Mn(DMS0)]2 and [HL.Cu2(MeO)2]2 , are reported (HL = 2-hydroxy-iV-

[2-({2-[(2-hydroxybenzoyl)amino]ethyl}amino)ethyl]benzamide and 2-hydroxy-A -[3-({3-[(2-

hydroxybenzoyl)amino]propyl}(methyl)amino)propyl] benzamide). The complex Hg

(MTCB)2 (MTCB=^-(morpholinothiocarbonyl)benzamide) and g (PTCB)2 (?TCB=N-

(piperidylthiocarbonyl)benzamide) have been synthesized and characterized by

elemental analysis, FT-IR, FT-Raman spectra and NMR methods. The complex,

Hg (MTCB)2, crystallizes in the triclinic space group P-1, vidth Z=2. The FT-Infrared and

FT-Raman spectra were used in study of the structures of MTCB, PTCB and their complexes

with mercury cation, which were agreement with the result of X-ray diffiaction.

Insoluble solid porous ethyl-2-iminobenzoate immobilized polysiloxane ligand system

of the general formula P-(CH2)3-NH(C6H4)COOC2H5, (where P represents [Si-0]„ siloxane

network) has been prepared by the reaction of 3-iodopolysiloxane P-(CH2)3-I with ethyl-2-

aminobenzoate. The modified polysiloxane derivatives; imino(A'-2-aminoethyl) benzamide

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P-(GH2)3-NH(C6H4)CONH(CH2)2NH2, and imino (iV-diethylenediamine)benzamide

P-(CH2)3-NH(C6H4)CONH(CH2)2NH(CH2)2NH2 ligand systems were prepared^^ '' ^ ''' ^ ' by

the reaction of ethyl-2-iminobenzoate ligand system with ethylenediamine and

diethylenetriamine respectively.

iV-(Morpholinothiocarbonyl)benzamide(Ci2Hi4N202S) and iV-piperidylthiocarbonyl)

benzamide(Ci3Hi6N20S) and their Co(III) complexes have been synthesized and

characterized^ '* by elemental analysis, FTIR and NMR methods. The complex

Co(Ci2Hi4N202S)3, crystallizes in the triclinic P-1 space group, with Z= 2, and unit cell

parameters, a = 12.080(7) A, 6= 12.195(7) A, c= 13.025(6) A, a = 90.198(7)°,

yS = 95.721(7)°, 7=106.426(9)°, F= 1830.4(17) A^ The antifungal activity of

A^-(piperidylthiocarbonyl)benzamide and its complex with cobalt (III)(ii)0re studied and

compared with N-(morpholinothiocarbonyl)benzamide against the major pathogens

responsible for important plant diseases {Botrytis cinerea, Myrothecium and Verticillium

dahliae dlebf^\

The reaction of Rh2(02CCh3)4 with an excess of molten PhC0NH2 gave

Rh2(PhCONH)4(PhCONH2)2 which contains a dirhodium unit having four bridging

benzamidato anions and two axial, neutral benzamide ligands. The compound has been

characterized by elemental analysis and infrared spectroscopic data ^ .

Approximately isomorphous crystal structures of two 18-crown-6 complexes were

determined with the sodium salt of N-(diiso-propoxyphosphoryl)benzamide(I) and with the

potassium salt of N-(di-iso-propoxyphosphoryl)thiobenzamide(II). Both I and II are (1:1:1)

guest-host complexes containing two different hosts (the crown ether and a bidentate

organophosphorus anion) and their common guest (an Na{sup+} or K{sup+} cation). Despite

a certain similarity between complexes I and II, significant structural distinctions between

them resulting from the difference in the ionic radii of Na{sup+} and K{sup+} cations were

revealed. In complex I, the Na{sup+} cation is hexa-coordinated, and in complex II, the

K{sup+} cation is octa coordinated^^ .

Applications of Benzamide and their Metal Complexes

Benzamide derivatives, known for their anti-inflammatory and immimomodulatory,

anti-timioural, antipsychotic and antiallergic activities are drugs widely used in

medicine ' . Benzamide derivatives which possess activities as vasopressin antagoustic

activity, vasodilating activity, hypotensive activity, activity for inhibiting growth of

mesagium cells, water diuretic activity, platelet agglutination inhinitory activity, oxotocin

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antagonistic activity and the like, to a pharamaceutical composition comprising the same and

to a method for the treatment and/or prevention of hypertension, heart failure, renal

insufficiency, edema, ascitges, vasopressin parasecretion syndrome, hepatocirrhosis,

hypomatremia, hypokalemia, diabetic, circulation disorder, oxytocin relating diseases^ ''

(e.g. premature delivery, dysmenorrhea!, endometritis, etc.) and the like in human beings or

animals.

Finding a suitable internal standard in reversed-phase high-performance liquid

chromatography is often difficult. A series of fifteen N-alkyl benzamides vvith a log P range

of 3.51 to 6.68 were synthesized as internal standards ^ ' ^ . The benzamide was found to be a

potent antimicrotubule agent in tobacco (Nicotiana tabaccum) cells. It strongly inhibited roof

growth and produced swollen club-shaped roots, an accumulation of cells in arrested meta

phase and loss of microtubules. A new class of antitubulin benzamides inhibits the growth of

fimgi, plants, mammalian cells, algae and protozoans^^ .

In an acute anti-inflammatory test, the cobalt chelate was most active

(31.1% inhibition) followed by the zinc and copper chelates, whereas the copper chelate

(22.3% inhibition) was most active in an adjuvant arthritis test. Again the cobalt chelate was

most active in the cotton-wad granuloma test. Gastric irritancy was markedly reduced after

chelation by copper, followed in order by zinc, cobalt, manganese and nickel chelates' ^ .

CI-994 or A -acetyldinaline [4-(acetylamino)-A^-(2-amino-phenyl) benzamide] is an

antitumor cytostatic agent currently undergoing clinical trial. Although several changes in

cellular metabolism induced by the drug have been characterized^^^^^^ ''' ^ '', the primary

molecular mechanism of its antitumor activity has been previously unknown. The results

show that CI-994 is a histone deacetylase (HDAC) inhibitor that causes histone

hyperacetylation in living cells. In assays of isolated enzymes, CI-994 inhibited HDAC-1 and

HDAC-2 in a concentration-dependent fashion but had no effect on the activity of the

prototypical histone acetyltransferase GCN5, Acetylated histone H3-specific Western blots

were used to monitor histone acetylation in HCT-8 colon carcinoma cells treated with CI-994

in vitro. CI-994 induced hyperacetylation of H3 in a time- and dose-dependent fashion.

H3 hyperacetylation was detectable as early as 30 min after the addition of CI-994 to cells.

These data demonstrate that inhibition of HDAC is an early event in cells treated with CI-994

and suggest that this inhibition is mechanistically related to the antitumor activity of this

compound .

36

The various N-acyl derivatives and N-Mannich bases of the model compound

L-pyroglutamyl benzylamide were synthesized to assess their suitability as prodrug forms for

the N-terminal pyroglutamyl residue occurring in several peptides, with the aim of improving

peptide delivery characteristics^^". Onkel et al synthesized novel class of benzimidazolium

chloride at high yield. The antimicrobial activities of three homologous series of

benzimidazoliimi chlorides against cocci, rods, fungi and bacillus have been measured^ '.The

antimicrobial activities of l-imdecyloxymethyl,3(lbenzimidazolmethylamino)pyridiniimi,

1 -undecyloxymethyl- and 1 -dodecyloxymethyl-3 - [ 1 (benzotriazol-1 -l)methylamino]

pyridinium chlorides exhibited strong activity and wide antibacterial spectra similar to the

activity of benzalkonium chloride^^\ A new complexes of lanthanide nitrates with 2-N-(6-

picolyl)-benzamide have been prepared and characterised ' by chemical analysis, infrared,

molar conductance and electronic spectral data. The complexes are active against bacterial

species, Bacilus subtilis, Escherichia coli and Pseudomonas fluorescence.

In psychiatry some substituted benzamides are therapeutically used as a newroleptics

and/or antipsychotrics. Indapamide, 3-(amino sulfonyl)-4-chloro-N-(2,3-dihydro-2-methyl-

N,4-indol-l-yl)-benzamide is an oral antihypertensive and diuretic agent.

N,4-methoxyphenyl benzamide were used as an antiallergic activity ' . Glibenclamide is a

second-generation oral hypoglycemic agent which is more potent than those of first group

(Lebovitz and Feinglos, 1983) and is used to assist in the control of mild to moderately severe

type II diabetes mellitus (adult, maturity-onset) that does not require insulin, but that can be

adequately controlled by diet alone.

A series of 4-amino-5-cliloro-2-methoxy-N-(l-substitutedpiperidin-4-ylmethyl)

benzamides were synthesized as novel gastroprokinetic agents.Tiapride(N-[2-

(diethylamino)ethyl]-5-(methylsulfonil)-o-anisamide) (TPD), is a substituted benzamide with

antipsychotic properties. It acts as antagonist of the dopamine D2 receptors, a property which

distinguishes this compoimd from other anti-psychotic agents '''*. Benzamide derivatives with

Cu", Co", Ni" and Zn" complexes are very active against the bacteria E.coli, Streptococus

aureus, Klebsiella pneumoniae, Salmonalla tyhi, Pseudomonas aeruginosa and Shigella

flexneri^'^^-^^^

I. 6 Mannich Bases and Related Metal Complexes Synthesized in Our Laboratory

In our laboratory studies on the preparation and characterization of some Mannich

bases and their interaction with transition metal ions have been carried out.

5-morpholinomethyluracil (MMU) and 5-morpholinomethyl2-^ouracil (MMTU) and its

37

complexes have been prepared and characterized by Kamalakarman and Venkappayya.

The ligands act as bidentate due to coordinating to the metal ion through carbonyl 0 and

morpholino N atoms. Sabastiyan^^^ and Venkappayya have prepared and characterized

1 -(N,N-dicycIohexylamino)methylthiourea (DCMT), 1 -(N,N-diethylammo)methylthiourea

(DEMT) and 1-piperidinomethylthiourea (PMT) and their complexes with Co", Ni", Cu",

Zn", Cd" and Hg" ions. Analytical spectral data support the bidentate behaviour of the

compounds chelating through thiocarbonyl sulphur and tertiary amino N donor atoms.

iV,V-Bis(morpholinobenzyl)urea (MBU) and its complexes have been prepared and

characterized by Venkatesa prabhu ^ and Venkappayya. Morpholinomethylurea (MMU) and

^orpholinomethylthiourea (MMT) and its complexes have been synthesized by Ramalingam

and Venkappayya. These three ligands MBU, MMU and MMT in the majority of their

complexes, chelated through carbonyl oxygen or thiocarbonyl sulphur and heterocyclic

nitrogen atoms '*" l The metal complexes of MBU formulated as [2MX2.L.4H20](X= CI",

Br', NOa', O.5SO4"" and CIO4") have been identified as the binuclear bridged complexes. The

ligand MBU is reported to be a bridging ligand with tetradentate behaviour bonding through

amide N and morpholine N each metal ion of the binuclear complexes.

Meenakshi ^^ and Venkappayya synthesized 3-methyl-2,6-diphenylpiperidine-4-one

(JVDDP), 3,5-dimethyl-2,6-diphenylpiperidine-4-one (DDP) and their complexes with Mn",

Fe"' and Co° ions. The various spectral datas confirms the bidentate coordination of the

ligands. Mohamed kasim and Venkatesa prabhu have synthesized and characterized

iV-(l-piperidinobenzyl)acetamide(PBA) and their complexes Mn", Co", Ni", Cu" Zn", Cd"

and Hg" ions. The complexes exhibit two types of stoichiometry, viz.[MX2L(H20)2] and

[MX2L2] pC=Cr, Br" and NO3") in which PBA acts as a bidentate ligand coordinating through

the oxygen of acetamide and nitrogen of piperidine moieties. Boopathy^^^ and Venkappayya

have synthesized and characterized the complexes of 4-morpholinomethylantipyrine (MMA)

and 4-pyrolidinomethylantipyrme(PMA) with Fe"^ Co", Ni", Cu", Zn", Cd" and Hg" ions,

both (MMA and PMA) act as a bidentate ligand coordinating through carbonyl oxygen and

morpholino (or) pyrrolidino nitrogen atoms. Manjula and Venkatesa Prabhu have synthesized

and characterized iV;iV^-bis(pyrrolidinobenzyl)urea(PBU), 7 -iV '-bis(pyrrolidinobenzyl)

thiourea (PBT) and JV-V-bis(morpholinobenzyl)thiourea (MBT) with Co", Ni", Cu", Zn",

Cd" and Hg" ions. The above ligands are bidentate in nature and the coordination takes place

through carbonyl O and amino N atoms.

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The literature survey on the morpholine, pyrrolidine, acetamide, benzamide,

acrylamide and their metal complexes reveals that there is no report on the Mannich bases of

acetamide, acrylamide and benzamide and their metal complexes which v e propose to

investigate.

Scope of the Present Work

1, To synthesise the following Mannich bases of acetamide, acrylamide and benzamide,

namely,

a) iV-[(Diphenylamino)methyl]acetaniide (DPAMAce)

b) iV-[Phenyl(pyrrolidin-l-yl)methyl]acetamide (PBA)

c) iV-[Morpholino(phenyl)methyl]acetamide (MBA)

d) A'-[(Diphenylamino)methyl]acrylamide (DPAMAcry)

e) A^-[Morpholino(phenyl)methyl]benzamide (MBB)

f) A^-[Phenyl(pyrrolidin-l-yl)methyl]benzamide (PBB)

2 To characterize the above compounds (ligands) using elemental analysis,

molecular weight determination and other physical tools such as IR,

UV-Visible, ' H NMR, '^C N M R and Mass spectral analyses.

3. To synthesize and characterize the complexes of the above ligands with transition and

some inner transition metal ions, such as V'^, Cr'", Mn", Fe", Co", Ni", Cu", Zn",

Cd", Hg", Ce , Th'^ and U^ by chemical analysis and by using various physical

methods.

4. To screen the ligands and some of their metal complexes for possible antibacterial,

antifungal and anticancer activities,

6. To screen the corrosion rate and inhibition efficiency of some ligands by weight

loss method.

7. To screen the metal ion removal from waste water by complexation method.

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