CHAPTER 3

AMINO ACIDS, N-BROMOPHTHALIMIDE - A BRIEF REVIEW

3.1 AMINO ACIDS- A BRIEF REVIEW

3.1.1 INTRODUCTION TO AMINO ACIDS

3.1.2 A BRIEF REVIEW ON OXIDATION OF AMINO ACIDS

3.1.3 REFERENCES

3.2 N-BROMOPHTHALIMIDE- A BRIEF REVIEW

3.2.1 GENERAL INTRODUCTION OF N-HALO REGENTS

3.2.2 INTERESTING FEATURE OF NBP

3.2.3 BRIEF REVIEW ON NBP OXIDATION

3.2.4 REFERENCES

3.1 AMINO ACIDS- A BRIEF REVIEW

3.1.1 INTRODUCTION TO AMINO ACIDS

Proteins are a group of complex nitrogen containing organic compounds

which occur in vegetable and animal cells. In addition to carbon, hydrogen,

oxygen and nitrogen, some proteins also contain sulphur. Proteins on

hydrolysis give a series of ill-defined fragments of decreasing complexity.

Such as proteoses, peptones, polypeptides and finally the constitutent units of

proteins, namely, the "amino acids". The amino acids which have been isolated

so far from protein hydrolysates are a-amino acids. RCH(NH2)COOH in which

an amino group (-NH2) and a carboxylic group (-COOH) are attached to the

same carbon atom. The character of the individual amino acid depends upon

the type of radical (-R) attached to the a-carbon atom. Chemistry of amino

acids consists of transformations of functional groups already present in this

molecules l-2, their hydrocarbon moieties (R) have not been subjected to

chemical reaction. The reason for this is obviously the high reactivity of

functional groups relative to the inertness of the hydrocarbon chain.

Amino acids are simple organic compounds. Their physical and

chemical properties are due to the presence of both acidic and basic groups in

the same molecule. Both inter and intramolecular interactions between the

basic and acidic functions play an important role in the properties of these

bifunctional compounds. Much of the interest in these small molecules has

been directed towards an understanding of their role as the building blocks of

peptides and proteins.

Enzymes and many harmones are also proteins. Amino acids are

obtained by the complete hydrolysis of proteins. Amino acids, its derivative

48

and peptides are important because their biological or theoretical significance

or important applications in chemistry or medicine. The number of papers

dealing with the synthetic, analytical or biomedical applications of 'Metal

complexes of Amino acids and peptides') has significantly increased in the past

few years.

Amino acids are classified according to the number of amino and

carboxylic group present in the molecule.

A. Neutral amino ~acids:

They have one amino and one carboxylic group in the molecule, e.g.,

glycine, alanine, valine, leucine, phenylalanine, etc.

B. Acidic amino acids:

They contain an additional carboxylic group, e.g., aspartic acid, glutamic

acid, etc.

C. Basic amino acids:

They contain excess of basic nitrogen, e.g., arginine, histidine, lysine,

etc. As amino acids contain both carboxylic and amino groups. They exhibit

acidic as well as basic properties, i.e., they are amphoteric in character. It has

been shown that neutral amino acids exist as inner salts with the dipolar

structure as H/NRCOO-. These are cafled "Zwitter ions". Amino acids are

known to exist in the following equilibria in aqueous solutions:

RCH(NH2)COOH ~ RCH(NH2)COO- + If'" ~ RCH(N+H))COO- (1)

Amino acid (S) Anion (S - ) Dipolar zwitter ion (SO)

The dissociation of amino acids depends on the pH of the media, the following

equilibria exist:

49

II' RCH(Nllz)COO' ~ RCII(NII) ')

OB' --OB'

Anion (S") Dipolar Zwitter ion (S")

(2)

Calion (Sill)

Oxidation of amino acids is of utmost importance both from a purely

chemical point of view and from the point of view of its bearing on the

mechanism of amino acid metabolism. The quantitative determination of each

of the component of amino acids produced during the hydrolysis of a protein is

very important in elucidating the structure of protein, because any theory of

protein structure must ultimately depend on an exact knowledge of all the units

contained in the molecule.

Naturally occurring amino acids are usually a-ami no-carboxylic acids,

a-amino acids are those in which the amino group is connected to the (alpha)

(number two) carbon of a carboxylic acid. Glycine, a-amino acetic acid is the

parent compound

NH2 I

H-C-COOH I H

a = amino acetic acid or glycine. ,

Substitution of one a-hydrogen atom by other leads to a variety of amino

acids. Many posses nonpolar hydro carbon groups at the a-carbon and other

contain more polar groups. Some even have an additional carboxylic or amino

group. The general formula of the amino acid is R-CH(NH2)COOH. Thus the

naturally occurring amino acids differ only in the nature of the side chain

residue R. This residue may be acidic, basic or neutral and either aliphatic,

aromatic or heteroaromatic in nature.

All members of the series with the exception of glycine (where R is

hydrogen) have an asymmetric carbon atom and hence optically inactive D-, L-

50

and optically inactive (racemic) DL-amino acids are possible. The naturally

occurring amino acids generally belong to the L-series.

3.1.2 A Brief Review on Oxidation of Amino acids

This type of oxidation study has been presented under different heads, as

follows-

1. Potassium Perrnanganate

In the oxidation of a-amino acids by Potassium perrnanganate in

moderately concentrate acidic medium. Verma et. a\.4 found that oxidation of

a-amino acid is proportional to the concentration of the amino acid in both

aqueous H 2S04 and HCl04 • They also observed that the rate of oxidation of

amino acid is greater in H2S04 than in HCI04• The faster rate of oxidation in

more concentrated H2S04 is due to protonation of the oxidant

Mn04' + H+-- HMn04

The kinetics of permanganic oxidation of DL-valine in concentrated

sulfuric acid (3.0-5.0 M) has been studied by spectrophotometrl. The rate law

found shows that reaction is auto catalyzed by Mn(H) concentration and acidity

of the medium has been analyzed. A reaction mechanism proposed according

to the experimental results.

2. Diperiodatonicketates

The kinetics of oxidation of some ammo acids [AA] with

diperiodatonicketate(IV) ion (DPN) in aqueous alkaline medium has been

studied6• The reaction follows first order with respect to each reactant i.e. [AA]

and [DPN]. The reactivity observed for different amino acids are :

phenylalanine> serine> glycine> leucine> a-alanine> valine > ~-alanine.

The reaction mechanism has been proposed.

·i!:2'!nat;]!~rt'mg!J . T22341 .

3. Acid Bromate and Positive Bromine

The oxidation of a-amino acids by acidified potassium bromate' in

aqueous acetic acid medium has first order dependency w.r.t. [BrCv)] and

[amino acid], where as in absence of sulfuric acid reaction could not take place

all. The cleavage ofC-H and N-H bond might take place for product.

4. CoCIII) aquo ion as an oxidant

Varadarajan and Hussani8 reported isokinetic relationship in the case of

CoCIII) oxidation of some amino acids and amino alcohols in aqueous acidic

medium.

Sethuram and Ra09 investigated Ag(l) catalyzed oxidation of a number of

amino acids by CoCIII). They suggested, Ag(l) forms an adduct with substrate

in a fast step. The adduct reacts with Co(III) in a slow step and giving another

(Ag2+-substrate) adduct which undergoes internal oxidation.

5. N-Chloramines or Positive chlorine

Moodithaya and Gowda 10 have studied kinetics of oxidation of amino

acid by N-chloramines in acidic water-methanol mixtures. N-chlorotoluene p­

sulphonamide is used as a source of positive chlorine. The reaction was studied

in perchloric acid medium. The rate dependence on [oxidant], [amino acid] and

[It] have been determined at 10%,20%,30%, 70% methanol for amino acids.

The rate generally shows second order kinetics in oxidant although in some

cases pseudo second order rate constant slightly decreases with increase in

methanol composition of the solvent while that in [W] rate remains almost the

same.

52

6. Hexacyanoferrate ion

Oxidation of glycine with alkaline potassium hexacyano ferrate

catalyzed by osmium tetraoxide was studied by Arvind and Mathur". The

reaction is first order w.r.t. substrate, alkali and catalyst while independent of

oxidant concentration. A mechanism involving the formation of amino acid

ferrocyanide complexes is fast step and its oxidation by Os(VIII) is slow step

has been proposedI2-13

•

7. Diperiodato-argentate (III)

The reaction of diperiodatoargentate(III) with glycine and related

compounds have been examinedl4• The monoperiodatosilver (III) species acts

as an active oxidant in comparison to that of diperiodatosilver (III) species.

These racetions consist of three kinetically distinguishable steps-induction

period, complexation and oxidation. Complexation of these substrates takes

place with a second order rate constant whereas the redox process occurs

except in case of cysteine with which these processes occurred by an order of

magnitude faster. The rate of electron transfer from carboxylic acids to the

silver(III) complex is observed to be several order of magnitude smaller in

comparison to that of amino acids. Both the rate of complexation and electron

transfer are influenced by the structure of the substrates. The aquated silver(III)

species is found to be more reactive in comparison to the hydroxylated silver

(III) species.

The kinetics of oxidation of p-alanine by

dihydroxydiperiodatoargentate(III) (DPA) in an alkaline medium was studied1s

by spectrophotometry in a temperature range of 298-318 K. The reaction rate

showed pseudo-first order dependence in the oxidant and 1 <nap < 2 in the

reductant. A plausible mechanism involving a pre-equilibrium of adduct

53

formation between the complex and reductant is proposed. The rate equations

derived from the mechanism explain all experimental observations. The

activation parameters along with the rate constants of the rate-determining step

were calculated.

The kinetics of Os(VIII) catalyzed oxidation of L-Ieucine by

diperiodatoargentate(III) (DPA) in alkaline medium at 298 K and a constant

ionic strength was studied spectrophotometricallyJ6. The oxidation products in

both the cases are pentanoic acid and Ag(I). The stoichiometry is, i.e., [L­

leucine]: [DP A] "" 1 :2. The reaction is of first order in Os(VIII) and [DP A] and

has less than unit order in both [L-Ieucine] and [alkali). The oxidation reaction

in alkaline medium has been shown to proceed via a Os(VIII)-L-leucine

complex, which further reacts with one molecule of MP A in a rate determining

step followed by other fast steps to give the products. The main products were

identified by spot test and spectral studies. The reaction constant involved in

the different steps of the mechanism are calculated. The activation parameters

with respect to slow step of the mechanism are computed and discussed and

thermodynamic quantities are also determined. The active species of catalyst

and oxidant have been identified.

Oxidation of L-serine and L-threonine by a silver(III) complex anion,

[Ag(HI06)2t, has been studied in aqueous alkaline medium17. The oxidation

products of the amino acids have been identified as ammonia, glyoxylic acid

and aldehyde (formaldehyde for serine and acetaldehyde for threonine).

Kinetics of the oxidation reactions has been followed by the conventional

spectrophotometry in the temperature range of 20-35 °C and the reactions

display an overall second-order behaviour: first order with respect to both

Ag(III) and the amino acids. Analysis of influences of [OK] and [periodate] is

observed second-order rate. A reaction mechanism is proposed to involve two

54

pre-equilibria, leading to formation of an Ag(I1I)-periodato-amino acid ternary

complex. The ternary complex undergoes a two-electron transfer from the

coordinated amino acid cations of the Ag(I1I) complex as a reagent for

modifications of pep tides and proteins are implicated.

8. Periodic acid and Periodates

According to Bakore and Shankerl8 Oxidation of amino acid by

periodates are mostly quantitative. Formaldehyde ,and glycollaldehyde and

ammonia were products of oxidation, when serine 3carbon was degraded with

periodates l9-2o at pH=5.5. The quantitative oxidation studies of amino

compounds show a significant difference in the behavior of aliphatic and

aromatic compounds when they are oxidized with periodates.

9 _ Aquomanganese (III)

The kinetics of oxidation of glycine by aquomanganese(III) ion in

HCI04 medium has been studied by Rajgopala et. eel at constant ionic strength

and different acidities. The reaction is first order in each [glycine] and

[manganic ion]. The rate is inversely proportional to the [W] at a lower

temperature (up to 45°C), but at higher temperature (55 to 65°C) rate becomes

proportional to the [Wr2. At a constant acid concentration the rate of reaction

is independent of [Mu(JI)]. This show that [Mn(IV)] is n.gt an active species in

this reaction. They suggested an outer sphere mechanism.

Oxidation of some a-amino acid and a-amino oxycarboxylic acid by

Mn(III) in H2S04-water mixture has been studied by Hiren and Kataria22

• They

found, the rate of reaction w.r.t. [Mn(III)] and [substrate] was unity, except

alanine which followed Michaelis-Menten type kinetics. The rate of reaction

decreases with increasing [H2S04] or [HCI04]. The order of reactivity of some

55

amino acids was observed as shown below: alanine < valine < leucine <

isoleucine < glycine < phenyl alanine (at 40° C).

In general, increase in the number of carbon atom in amino acid

increases the rate of oxidation (except glycine). Rate for phenylalanine is high

because of the involvement of phenyl group. Similar results were obtained by

Chandraju and Mahadevappa23 in the study ofL-serine, phenylalanine, alanine,

valine, threonine in pyrophosphate medium.

10. Pyridinium Bromochromate

Oxidation of a-amino acids by pyridinium bromo chromate (PBC)24 was

studied in acetic acid-water mixture containing perchloric acid. The reaction

rate is first order in [PBC] and inverse first order in [W] and has aldehyde as a

product. Michaelis-Menten type kinetics has been observed with respect to a­

amino acids. The rate of reaction increases with a decrease in the polarity of

solvent indicating an ion-dipole interaction in the slow step. The reaction

exhibit no primary kinetic isotope effect. The activation parameters have been

evaluated. The reaction mechanism involving the formation of chromate-ester

between unprotonated PBe and unprotonated amino acid followed by C-C

bond fission in the slow step has been suggested. The value of the Michaelis

constant (substrate-oxidant complex formation constant) increases as the

number of carbon atoms increases in the amino acid.

Kinetics of oxidation of glycine by pyridinium bromochromate «(PBCi5

have been studied in aquo-acetic acid medium in presence of perchloric acid.

The products are ammonia, CO2 and formaldehyde. The reaction shows first

order kinetics in [PBC] , inverse order with respect to [W] and Michaelis­

Menten type kinetics with respect to [glycine]. The rate of oxidation decreases

with increase in dielectric constant of solvent indicating ion-dipole interaction.

56

Activation parameters have been evaluated. Mechanism involving C-C fission

has been suggested.

11. N-Chloronicotinamide

Kinetics of oxidation of ten a-amino acids by N-chloronicotinamide

(NCN?6 in aqueous acetic acid medium in presence of hydrochloric acid have

been investigated. The' observed rate of oxidation is first order in both [NCN]

and [HCl]. A small increase in rate is observed with increase in [amino acid]. A

decrease in the dielectric constant of the medium increases the rate. Addition of

nicotinamide (NA), the reduction product of NCN, has a retarding effect on the

rate of oxidation. The corresponding aldehydes, ammonia and carbon dioxide

have been identified as the oxidation products. Molecular chlorine has been

postulated as the reactive oxidizing species in the reaction.

12. Chloramine-T

Kinetics of oxidation of a-amino acids, glycine, valine, alanine and

phenylalanine by sodium N-chloro-p-toluenesulfonamide27 or chloramines-T

(CAT) has been investigated in perchloric acid medium at 30°C. The rate

shows fir~t-order dependence on both CAT and amino acid concentrations and

an inverse first-order on [W]. The variation of ionic strength and the addition

of p-toluenesulfonamide and cr ion had no effect on the reaction rate.

Decrease of dielectric constant of the medium by increasing the MeOH content

decreased the rate. Rate studies in D20 medium showed the inverse solvent­

isotope effect observed. Proton-inventory studies were carried out using H20-

D20 mixtures. The activation parameters have been computed. The proposed

mechanism and the derived rate law are consistent with the observed kinetic

data. The rate of oxidation increases in the following order: gly<val<phe<ala.

57

13. N-Bromo-p-toluenesulfonamide

The kinetics of oxidation of a typical dipeptide glycylglycine (GO) by

bromamine-T28 have been studied in perchloric acid medium at 40°C. The rate

shows first-order dependence on [BATJo and is fractional order in [00]0 which

becomes independent of [00]0 at higher [OOJo. At [it]>O.02 M, the rate is

inverse fractional in [W] but is zero order at lower [it]<O.02 M. Variation in

ionic strength or dielectric constant of the medium had no significant effect on

the rate. The solvent-isotope effect was measured. Proton inventory studies

have been made. The reaction has been studied at different temperatures and

activation parameters have been computed.

The kinetics of oxidation oED-cycloserine (CS) by sodium-N-bromo-p­

toluenesulfonamide or bromamine-T29 (BAT) in the presence of HCI at 313 K

follows the rate law, -d[BAT]/dt=k[BAT][CS]'[HCIJY, where x and yare less

than unity. The decrease in dielectric constant ofthe medium increases the rate.

The variation of ionic strength or the addition of the reaction product, p­

toluenesulfonamide, has no effect on the rate. The rate increases in D20

medium and the inverse solvent-isotope effect was observed. Composite

activation parameters for the reaction have been determined from Arrhenius

and Eyring plots. Michaelis-Menten type of kinetics is observed and activation

parameters for the rare determining step have been computed. The proposed

mechanism assumes the simultaneous catalysis by it and cr ions and is

consistent with the observed kinetic data. Products of oxidation were identified.

14. N-Bromobenzenesulphonamide

Kinetics of oxidation of acidic amino acids glutamic acid (Glu) and

aspartic acid (Asp) by sodium N-bromobenzenesulphonamide (bromamine-B

or BAB)30 has been carried out in aqueous perchloric acid medium at 30oe.

58

, ,

The rate shows first order dependence each on [BABlo and [amino acid]o and

inverse first order on [Hl Succinic and malonic acids have been identified as

the products. Variation of ionic strength and addition of the reaction product

benzenesulphonamide or halide ions had no significant effect on the reaction

rate. There is positive effect of dielectric constant of the solvent. Proton

inventory studies in H20-D20 mixtures showed the involvement of a single

exchangeable proton of the OH' ion in the transition state. Kinetic

investigations have revealed that the order of reactivity is Asp>Glu. The rate

laws proposed and derived in agreement with experimental results are

discussed,

Kinetic studies of the oxidation of L-isoleucine (ISL) and L-ornithine

hydrochloride (ORH) by sodium N-bromobenzenesulphonamide (bromamine­

B or BAB/1 were studied in aqueous perchloric acid medium. The rate shows

first order dependence on both [BAB]o and [amino acid]o and inverse first

order dependence on [W] for ISL and first order dependence on err] for ORH.

The rate of reaction decreased with decreases in the dielectric constant of the

medium. The addition of benzenesulphonamide (BSA), which is one of the

reaction products, had no effect on the reaction rate. The rate remained

unchanged with the variation in the ionic strength of the medium for ISL,

whereas the rate decreased with increases in the ionic strength of the medium

for ORH. Isovaleronitrile and 3-(methylamino )propionitrile were identified as

the products. Thermodynamic parameters were computed by studying the

reactions at different temperatures. The rate laws derived are in excellent

agreement with the experimental results. Plausible mechanisms are suggested.

S9

15. N-Bromosuccinimide

Kinetics of oxidation of amino acids(AA) and dipeptides(DP) by N­

bromosuccinimide (NBS)32 was studied in the presence of perchlorate ions in

acidic medium at 2SoC. The reaction was followed spectrophotometrically at

240 nm. The reactions follow identical kinetics, being first order each in

[NBS], [AA] and [DP]. No effect on [W], reduction product [succinimide] and

ionic strength was observed. Effects of varying dielectric constant of the

medium and addition of anions such as chloride and perchlorate were studied.

Activation parameters have been computed. The oxidation products of the

reaction were isolated and characterized. The proposed mechanism is

consistent with the experimental results. An apparent correlation was noted

between the rate of oxidation of AA and DP.

The kinetics of oxidation of p-alanine by N-bromosuccinimide33 has

been studied electronically at 25°C. The energy of activation, frequency factor

and entropy of activation are calculated. The specific reaction rate is influenced

by hydrogen ion concentration and dielectric constant of the medium. The most

probable mechanism has been suggested.

The kinetics and mechanism of Ru(III) catalyzed oxidation of

asparagines and aspartic acid by N-bromosuccinimide34 have been investigated

in acidic medium in the presence of mercuric acetate as a scavenger in the

temperature range 30-4SoC. The reactions follow identical kinetics. The

observed rate of oxidation is first order in [NBS], [substrate] and [Ru(I1I)]

respectively. A small increase in rate is observed with increase in [KCI].

Additions of succinimide and acetic acid have retarding effect on the rate of

oxidation. Negligible effects of mercuric acetate, ionic strength and [W] have

60

been observed. Various activation parameters have been calculated. The

mechanism of the reaction is discussed in terms of kinetic results.

16. Ag(II)

The oxidation of glycine, several other amino acids and carboxylic acids

by Ag(II) has been studied35. Transient spectra, kinetics and product analysis

indicate that the mechanism involves two steps. The first step is formation of a

complex between Ag(II) and the substrate. The second step is an electron

transfer from the carboxyl group to the Ag(II) within the complex. As a result,

the substrate undergoes decarboxylation. The rate constants for complexation

and oxidation were determined for a variety of substrates and with different

forms of Ag(II), i.e., aquo, hydroxo and amino complexes. Both steps of the

mechanism are affected by the structure of the substrate, for example, by the

electron-donating properties of methyl groups and electron withdrawing by the

NH3 + group. The rate of electron transfer within the complex is also affected by

the structure and stability of the complex.

17. Chromium (III)

The kinetics of the chromium(III) catalyzed oxidation of L-Ieucine and

L-isoleucine by alkaline permanganate were studied and compared,

spectrophotometrically36. The reaction is first order with respect to (oxidant)

and (catalyst) with .an apparently less than unit order in (substrate) and zero

order with respect to (alkali). The results suggest the formation of a complex

between the amino acid and the hydroxylated species of chromium(III). The

complex reacts further with the permanganate in a rate-determining step,

resulting in the formation of a free radical, which again reacts with the

permanganate in a subsequent fast step to yield the products. The reaction

constants involved in the mechanism were obtained. There is a good agreement

61

between observed and calculated rate constants under different experimental

conditions. The activation parameters with respect to slow step of the

mechanism for both the amino acids were calculated and discussed. Of the two

amino acids, leucine is oxidized at a faster rate than the isoleucine.

18. Copper (III)

The kinetics and mechanism of oxidation of aspartic acid by the

bis(hydrogen periodato) complex of Cu(I1I), [CU(Hl06)2]5., is studied in an

alkaline medium37. The reaction rate is first order with respect to Cu(III) and

fractional order with respect to aspartic acid. The value of the observed rate

constant is found to decrease with the increase in concentrations of either OH'

or 104-, There is a positive salt effect, and the free radical has been determined.

In view of these kinetics phenomena, a plausible mechanism is proposed and

the rate equations derived from the mechanism can explain all experimental

results. The activation parameters along with the rate constants of the rate­

determining step are calculated.

19. Ruthenium (III)

The kinetics of the Ru(III)-catalyzed oxidation of L-leucine and L­

isoleucine by alkaline permanganate were studied and compared,

spectrophotometrically using a rapid kinetic accessory38. The reaction is first

order with respect to [oxidant] and [catalyst] with an apparently less than unit

order in (substrate] and (alkali] reapectively. The results suggest the formation

of a complex between the amino acid and the hydroxylated species of

ruthenium(III). The complex reacts further with the alkali permanganate

species in a rate-determining step, resulting in the formation of a free radical,

which again reacts with the alkaline pennanganate species in a subsequent fast

step to yield the products. The reaction constants involved in the mechanism

62

were calculated. There is a good agreement between observed and calculated

rate constants under different experimental conditions. The activation

parameters with respect to the slow step of the mechanism for both the amino

acids were calculated and discussed. Of the two amino acids, leucine is

oxidized at a faster rate than isoleucine.

The kinetics of the ruthenium(III) catalyzed oxidation of L-alanine by

alkaline permanganate was studied spectrophotometrically using a rapid kinetic

accessory39. The reaction is first order with respect to [oxidant] and [catalyst]

with an apparent less than unit order in [substrate] and [alkali] respectively.

The results suggest the formation of a complex between the alanine and the

hydroxylated species of ruthenium(III). The complex reacts further with the

alkaline permanganate species in a rate-determining step, resulting in the

formation of a free radical, which again reacts with the alkaline permanganate

species in a subsequent fast step to yield the products. The reaction constants

involved in the mechanism were calculated. There is a good agreement

between observed and calculated rate constants under different experimental

conditions. The activation parameters with respect to slow step of the

mechanism were calculated and discussed.

20. Uranium (VI)

The complexation of uranium(VI) with the amino acids L-glycine and L­

cysteine has been investigated by time-resolved laser-induced fluorescence

spectroscopy (TRLFS) and UV-Vis spectroscopy at a low pH range40

• The

identified 1: 1 and 1:2 uranyl-L-glycine complexes fluoresce and have similar

absorbance properties. In contrast to the glycine system, uranyl forms two

different non-fluorescent I: 1 complexes with L-cysteine, showing individual

absorbance properties under the given experimental conditions. The

63

corresponding complex fonnation constants were calculated using the

spectroscopic data.

64

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26. K. Vivekanandan and K. Nanbi, 1. Ind. Chern. Soc., 1999, 76, 198.

27. K.S. Rangappa, K. Manjunathaswamy, M.P. Raghavendra and N.M.M.

Gowda, Int. J. Chern. Kinet., 2002,34,49.

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63.

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2000, 93(2), 115.

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Nagaraja, Turk1. Chern., 2003,27,571.

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66

2005,232,21.

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67

3.2 N-bromophthnlimide - A brief revielV

3.2.1 General introduction of N-hnlo reagents

Several oxidizing agent specific and selective to varying degree, have

been added to the literature of oxidation of organic and inorganic compounds.

N-halo compounds, when reacting with olefins add bromine to the double

bonds or act as source of hypohalous and acid in aqueous solution. Credit for

first reporting this observation goes to Wohll. N-bromoacetamide was thus

used as an agent for allylic bromination. Zigler et. al extended the idea and in

1942 used N-bromosuccinimide for allylic bromination. The work was

generalized and was named 'Wohl-Zigler' reaction2•

In addition to metal cation oxidants, the other groups that have received

much attention are known as N-halogeno compounds. Originally these

compounds were known for their halogenating property but now are known for

their diverse nature due to their ability to produce halonium ion, hypohalite

species or N-anions etc. These compounds include N-haloamides and imides

and N-halogeno metallo compounds.

N-haloimides are stronger oxidizing agents as compared to N­

haloamides, the former being more acidic, looses halogen atom as halonium

ion which is an electrophile and further, the resulting anion is stabilized by

resonance. Hence, such compounds undergo heterolytic fission to produce

halonium ion rather than halogen free radicals. Owing to this reason these

compounds are not good allyJic halogenating reagents but are good oxidants.

This field has become an interesting field of research and number of

workers did much work about the chemistry of N-halo compounds. For

example Bromamine-T3, Chloramine-T4

, N-bromoacetamide5

, N-

bromosuccinimide6, N-chloroacetamide7, N-iodosuccinimide8, N-

bromophthalimide9, N-bromobenzamide lO and Bromamine-B

il have been

68

successfully tested as halogenating agents oxidizing agent and dehydrating

agents. The application of N-halo reagents (such as N-halo amines, N-halo

ami des and/or imides, N-halo sulfonamides and/or imides, and etc.) in various

organic functional group transformations such as: oxidation reactions,

deprotection and protection of different functional groups, halogenations of

saturated and unsaturated compounds, acylation of alcohols, phenols, amines or

thiols, epoxidation of alkenes, aziridination and etc. The chemistry of N-halo

reagents was the subject of several review articlesI2-18

•

3.2.2 Interesting feature of NBP

N-bromophthalimide has very active polar N-Br bond. Therefore, NBP

has diverse nature due to its specific property as it provides free NBP,

(NBPHt, Br+, HOBr, H20Br+ and other species in acidic medium, where as in

the absence of mineral acids, it provides very reactive oxidizing species.

h c. h . . h' . d 19-29 T ere lore, t ese reagents mteract WIt varIOus orgamc compoun s .

NBP+W ~ NHP+Br+

NBP + W ~ (NBPHt

HOBr + W ~ (H20Brt

N-bromophthalimide has been used in organic synthetic methodology

especially in the oxidation and bromination reactions. In most cases these

reagents are converted to phthalimide in the end of reactions, as a nontoxic

chemical.

69

3.2.3 Brief review on NIW Oxidntion

Kinetics and mechanism of oxidation of Dimethyl sulphoxide by N­

bromophthalimide (NOP) in aqueous acetic acid in presence of mercuric

acetate has been studied by Bhavani and Lil/o.

The rate law is found to be

(-dldt) [NBP] = k2 [NOP] [Sulphoxide]

Addition of neutral salt does not have any pronounced effect on the reaction

rate. The reaction is found to be insentive to [I-f] ion. They proposed the

reaction mechanism for this oxidation process. There may be a possibility that

three oxidizing species viz. NBP it self of protonated NBP as (NOPH+) and

hydrolysis product HOBr. They proposed a mechanism (scheme-}) in which

the rate determining step involves the direct attack of the bromine atom of the

NBP on the sulphur atom of the sulphoxide giving a positively charged

intermediate. Which by subsequent attack of the water molecule in a fast step

gives dimethyl sulphone.

70

~ HC OC C

,,-3 "'5 -0 I slowest / - + N-l3r ..

H3C ~ / C

II o

Br +

H3C",1 OH

fast H3c",11 5=0 + Hp ..

/e 5=0 + H++ Br" /e H3C H3C

OH

H3C", I H3C\ fast -:;::::-0

5=0 .. /5~0 +W

H3C/ H3C

0 0

" II

~ c"-- ~ C"--N- + W .. N-H

~ ~/ ~ ~/ 0 0

Scheme-l

C"" N-

~/ o

Mohan das and coworkers3! have developed direct potentiometric

titration using N-bromophthalimide as an oxidant for the determination of a

71

variety reducts such as As{I/I), Sb{III), Fc{II), hexacY:lOoferrote{II), iodide,

ascorbic acid, hydroquinone, hydrazine, phenylhydrazine, bcn7Jlydrazide,

isonicotinic acid hydrazide, semicarbazide, thiosemicarbazidc, thiourea,

aniline, phenol, oxine and its metal complexes, and anthranilic acid and its

metal complexes. The potentiometric determination of antipyrine and some of

its lanthanide complexes of the types [Ln(ap)3(N03)3l and [Ln(aphl(CI04h,

where Ln = La, Pr, Nd, Sm, Gd, Tb, Dy, Ho and Y and ap = antipyrine using

N-bromophthalimide was described by Mohandas and coworke~2.33.

Amatul and coworkersJ4 have studied the kinetics of oxidative

deamination of aliphatic amines by N-bromophthalimide in aqueous acetic acid

medium. Kinetic observations indicate first order in diethylamine (DEA) and

triethylamine (TEA) and fractional order in methylamine (MA), n-propylamine

(PA) and n-butylamine (BA). In all cases an inverse fractional order in [ttl has

been noticed. The stoichiometry of NBP amine oxidation reaction could

represented as 2[NBP] : I [amine 1 on the basis of estimated result.

2 NBP + Amine - Aldehyde + NH3 + Br2 + 2 Phthalimide

On the basis of observed kinetic features and foregoing discussion a plausible

mechanism is proposed and given in the (scheme-2)

72

" 5- 5.

" C)O /I

0("" '~ Dr 11_/ ~ I I,. R-I-N-II + ~ I /N-Dr ~- ~~'J.\:\ I # II C

II I 5~ II 0 II 0

(NBP) (Complex C)

0

II ~ C"'-.. 1-N-H + HBr R-C=NH - R-C=O + Nil)

~ IT/' I I H II

0

Scheme-2

The rate law (constant [It] and ionic strength) for the above mechanism is

given in Eq.(1)

-d In [NBP] = k' = kK [amine] (1)

dt 1 + K [amine]

The rate law (constant [It] and ionic strength) for DEA and TEA·system

(formation constant (K) is small) comes out as Eq.(2):

-d [NBP]

dt = k" [NBP][amine) (2)

(where k" = k K)

Puttaswamy and coworkers35 have studied the kinetics and mechanism

of oxidation of aspirin by bromamine-T, N-bromosuccinimide and N­

bromophthalimide in aqueous perchloric acid and reported that the oxidation

reaction follows identical kinetics with first order in [oxidant], fractional order

73

in [aspirin] and inverse fractional order in [W]. The rate decreased with

decreasing dielectric constant of the medium.

Nair and coworkers36 have studied the effect of cyc10dextrin on the

oxidation of acetophenone

bromophthalimide in aqueous

and substituted acetophenone by N­

acetic acid medium and reported that the

reaction is zero order in [oxidant] and first order in [substrate]. Increase in [H+]

increases the rate with a fractional order dependence and given in the (scheme-

3)

C6H5

K CH3 + H+ ~ C6Hs--~-- CH3

+ O--H

H

rl k\ C .. CH2 C6H5 r=CH2 + H30 +

I:) slow

0 OH H

+ HOBr -r Product ast

so that dx = k\ [C6H5-C-CH21 = K\ Keq [C6HsCOCH31 [Wl dt II

OH+

Scheme-3

74

supports reaction by HOBr.

Zachariah37

have studied a comparative study of the oxidation of

benzaldehyde in aqueous acetic acid medium in presence of mercuric acetate

and reported that the rate is first order with respect to both the [substrate] and

[oxidant]. The dielectric constant of the medium has a positive influence and

given the (scheme-4)

H C H - c/ +

6 5 / "-

OH OH

/ K z Br-N

"-

k3 -Slow

·0

II "-C6HsC-OH + II' +Br' + / NH

Scheme·4

The interaction of HOBr with either the aldehyde or its diols is less feasible

since the O-Br bond of HOBr should be first broken to give Br+ and Olf. But,

the Br+ ion formation is much more facile in the case of >NBr as N is highly

electronegative owing to the influence of its neighbouring groups in the ring.

Further, the breaking of the O-H bond of the substrate to discard the proton

which again attaches to the negative oxygen to form -OR bond is not

convencing. Based on these facts, a plausible mechanism would be proposed in

(scheme-4).

75

Srinivas and coworkers3! have studied the kinetics and mechanistic

aspects of oxidation of acetophenone by N-bromophthalimide in presence of

mercuric acetate and reported that the reaction kinetics were first order in

[NBP] and fractional order in [acetophenone]. The decrease in dielectric

constant of the solvent, the rate of oxidation was decreased.

Thiagarajan and coworkers39 studied the oxidation of some a­

hydroxyacids (mandelic acid, lactic acid, malic acid, benzilic acid and atrolatic

acid) by N-bromophthalimide in pH of the medium. It was of interest to

determine whether the alcoholic OH or the carboxylic 01-1 is involved in the

oxidative decarboxylation of a-hydroxy acids which have bifunctional groups.

Recently, Reddy and coworkers40 has studied the inhibitory effect of

ruthenium(III) on the oxidation of dimethyl sulfoxide by N-bromosuccinimide

and N-bromophthalimide in the presence of mercuric acetate in aqueous acetic

acid. The reaction order is first with respect to the [oxidant] and [substrate], but

less than one at low substrate concentrations and fractional for higher

concentrations. The effect of the ionic strength of the medium is negligible,

while that of the dielectric constant is positive.

Recently, Srinivas and coworkers4J has studied the oxidation of aromatic

carbonyl compounds by N-bromophthalimide in mercuric acetate system.

Aromatic carbonyl compounds are efficiently converted into the corresponding

benzoic acids under mild reaction conditions by N-bromophthalimide and

mercuric acetate in good to excellent yields. This procedure works efficiently

at room temperature for aromatic aldehydes as well as aromatic ketones to give

the corresponding benzoic acids.

Very recently, Srinivas and coworkers42 has studied the oxidative

kinetics of benzaldehydes, viz., 4-bromo, 4-chloro, 4-methyl, 3-nitro

benzaldehydes by N-bromophthalimide in presence of excess of mercuric

76

acetate in aqueous acetic acid medium. Results of detailed kinetic effects, viz.,

solvent, temperature, concentration and salt effects, support the Michaelis­

Menten type of mechanism. The stoichiometric ratio of N-bromophthalimide:

benzaldehyde, was 1: 1. The product of oxidation was benzoic acid, which was

confirmed by spot tests. Thermodynamic and activation parameters have been

presented. Effect of substituents has been dealt with and order of reactivity

established.

77

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