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
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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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