CHAPTER – II

OXIDATION OF PIPERAZINES BY BROMAMINE-B IN ACIDIC BUFFER

MEDIUM: A KINETIC AND MECHANISTIC STUDY

60

SECTION 2.1

INTRODUCTION TO PIPERAZINES

Piperazine is a heterocyclic nitrogenous compound and has chemical

similarity with piperidine, as it has opposing nitrogen atoms in the ring. It was first introduced as an anthelmintics drug in 1953. Piperazine exists as small alkaline deliquescent crystals with saline taste. It is a broad class of chemical compounds, many with important pharmacological properties.

N

N

H

H

N

N

H

CH3

N

N

H

CH3 Piperazine 1-Methylpiperazine 1-Ethylpiperazine

Piperazine is freely soluble in water and ethylene glycol, but insoluble in diethyl ether. It is a weak base with a pKb of 4.19 [1]. Piperazine readily absorbs water and carbon dioxide from air. Piperazine itself can be synthesized by reacting alcoholic ammonia with 1,2-dichloroethane, by the action of sodium and ethylene glycol on ethylene diamine hydrochloride or by reduction of pyrazine with sodium in ethanol. Two common salts in the form of which piperazines are usally prepared for pharmaceutical or veterinary purposes are the citrate and adipate [2]. Piperazine is formed as a co-product in the ammoniation of 1-2-dichloroethane or ethanolamine [3]. A large number of piperazine compounds have anthelmintic action. Piperazines are also used in the manufacture of plastics, resins, pesticides, brakefluid and other industrial materials. Piperazine is a main moiety of psychoactive drugs. Certain piperazine derivatives are suspected of ecstasy substitutes. Benzyl piperazine is banned in many countries. Benzyl piperazine has been used as an anthelmintic (antiparastic effect). Nitrogen in piperazine ring plays an important role in biological research and drug manufacturing industry including the preparation of anthelmintic, antiallergic, antibacterial, antihistamic, antiemetic and antimigraine agents. Piperazine ring and piperazine derivatives are important cyclic components in industrial field, as raw materials for hardner of epoxy resins, corrosion inhibitors, insecticides, accelerators for rubber urethane catalysts and antioxidants.

61

1-Methylpiperazine

1-Methylpiperazine is soluble in water with boiling point 138°C, melting point-6°C.

and molecular mass of 100.16. It is used as an intermediate for antibiotics

(quinolones) and pharmaceuticals (Eg: Antihistamines and tranquilizers). It is also

used for the production of agro chemicals, surfactants, dyestuffs, pigment and other

organic chemical compounds.

1-Ethylpiperazine

1-Ethylpiperazine is soluble in water with boiling point 157°C melting point -60°C

and molecular mass 114.19. 1-Ethylpiperazine is used in the synthesis of drugs like

enfloxacin, dyes, agrochemical and other chemical compounds.

62

SECTION 2.2

OXIDATION OF PIPERAZINES: A REVIEW

Stephanie et al. [4] have reported the oxidation of aqueous piperazine (PZ),

oxidation rates, products and high temperature oxidation. The major, identified

oxidation products of PZ are EDA, fluoropiperazine (FPZ), formate, NH4+, oxalate

and oxalyl amides. Minor products include acetate, acetylamides, other formyl

amides, nitrite, and nitrate when PZ is heavily oxidized.

Aravindakshan et al. [5] have reported kinetics of non-isothermal

decomposition of polymeric complexes of N, N´-bis (dithio-carboxy) piperazine with

iron(III) and cobalt(III). Thermogravimetry, in conjunction with differential

thermogravimetry and differential thermal analysis has been used to investigate the

kinetics of thermal decomposition of polymeric complexes of N, N´-bis (dithio

carboxy) piperazine with Fe(III) and Co(III) in air. The results indicate that the values

of kinetic parameters obtained using the Coats-Redferrn, Freeman-Carroll and

Horowitz-Metzger equations are reasonable and in good agreement. It has also been

found that the decomposition processes of both the complexes follow first order

kinetics.

Yutaka et al. [6] have reported rhodium-catalyzed reaction of N-(2-pyridinyl)

piperazines with CO and ethylene which leads to a novel carbonylation at a C-H bond

in the piperazine ring. The reaction of N-(2-pyridinyl) piperazines with CO (15 atm)

and ethylene in the presence of catalytic amount of Rh4(CO)12 in toluene at 160°C

resulted in a novel carbonylation reaction, which involves dehydrogenation and

carbonylation at a C-H bond. The carbonylation takes place regioselectively at a C-H

bond to the nitrogen atom substituted by a pyridine. The presence of an additional

nitrogen functionality at the 4-position of the piperazine ring is also essential for the

reaction to proceed. The electronic nature of substituents, the substitution of an

electron-donating group on the 4- nitrogen causes an increase in the reactivity, as does

the substitution of an electron-withdrawing group in the pyridine ring. It is found that

the reaction involves the following two discrete reactions: (i) Dehydrogenation of the

piperazine ring and (ii) Carbonylation at a C-H bond in the resulting olefin. The

63

reaction proceeds via two cleavages of the C-H bond, first at the sp3 C-H bond and

then at the sp2 C-H bond. The reaction stops at the dehydrogenation step by

replacement of the pyridinyl group with a phenyl group.

Dong et al. [7] have reported the effect of piperazine on the kinetics of carbon

dioxide with aqueous solutions of 2-amino-2-methyl-1-propanol. The absorption of

CO2 into aqueous mixtures of 2-amino-2-methyl-1-propanol (AMP) and piperazine

was investigated. A wetted-sphere absorption apparatus was used to measure the

absorption rate. The absorption rates of CO2 into aqueous solutions of AMP in the

range of 0.55-3.35 kmol/m3 were measured. The experimental temperatures were 303

and 313K. The zwitter ion deprotonation mechanism was used to interpret the kinetic

data of aqueous solutions of AMP. The apparent reaction rate constants increased

with the addition of piperazine. The effect of piperazine on the reaction rate of CO2

with aqueous solutions of AMP consists of the contribution for the zwitter ion

deprotonation and the direct reaction of piperazine with CO2. The zwitter ion

deprotonation constants of all bases presented in liquid and the direct reaction rate

constant of piperazine were obtained.

Jiri and Mirostav et al. [8] have studied kinetics of ethylene diamine and

piperazine ethoxylation. The ethoxylation of ethylenediamine and piperazine was

studied in the temperature range 343 -363K in the presence of 0-10% water. Kinetic

parameters of all reactions occuring in the system and a factor describing the water

effect on the rate of the reaction are given. No formation of quaternary bases was

observed.

Vaidya and Junghare et al. [9] have reported the acceleration of the wet

oxidation reaction of piperazine by heterogeneous Ru/TiO2 catalyst. Wet air oxidation

is a candidate technique for the effective treatment of waste water contaminated by

nitrogenous organic pollutants. Piperazine (PZ) is a cyclic diamine representing this

class of compounds. In the present work, the wet oxidation reaction of PZ was studied

for the first time. It was found that, in the studied range of temperatures of

180°- 2300C and O2 partial pressures of 0.69-2.07 mpa, the oxidation process was

slow, the total organic carbon (TOC) conversion at 230°C and 0.69 mpa, O2 partial

64

pressure was just 52% after 2 hours. The investigated reaction was accelerated by a

heterogeneous Ru/ TiO2 catalyst, maximum TOC conversion (91%) was achieved

during catalytic wet oxidation at 210°and 1.38 mpa, O2 pressure. Kinetic data were

collected over the range of temperatures 180°-210°C, O2 partial pressures 0.34-1.38 mpa,

and catalyst, loading 0.11-0.66 kg / m3. The lumped TOC concentration decay was a

two step first order process.

65

SECTION 2.3

KINETICS OF OXIDATION OF PIPERAZINE, 1-METHYLPIPERAZINE AND 1-ETHYLPIPERAZINE BY BROMAMINE-B IN ACIDIC BUFFER (pH 4.0) MEDIUM

This section reports the kinetics of oxidation of piperazine (PZ), 1-methylpiperazine (MPZ) and 1-ethylpiperazine (EPZ) by bromamine-B in acidic buffer medium (pH 4.0) at 303K. Kinetic measurements

Kinetic runs were performed under pseudo first order conditions of a large excess of the substrate over BAB at 303K. For each run, requisite amounts of piperazine, 1-methylpiperazine, 1-ethylpiperazine, NaClO4 (to maintain constant ionic strength) and a buffer of known pH were mixed in a stoppered Pyrex glass tube whose outer surface was coated black. Required amount of buffer was added to maintain a constant total volume. The tube was thermostated in a water bath at a given temperature. To this solution, was added a measured amount of pre-equilibrated BAB solution to give a known overall concentration. The reaction mixture was shaken for uniform concentration. The course of the reaction was monitored iodometrically by titration of unreacted BAB in known aliquots (5 ml each) of the reaction mixtures withdrawn at regular time intervals for two half lives. The pseudo first order rate

constants (k´) calculated were reproducible within ± 3%.

Stoichiometry and product analysis

Varying ratios of oxidant piperazine in the presence of pH 4.0 buffer were equilibrated at 303K for 24 hours. The unreacted BAB in the reaction mixture was determined iodometrically, indicated that one mole of piperazine consumed one mole of BAB to give the corresponding N-oxide. The stoichiometric reaction is represented by the equation given below.

N

NHO

R

C 4H 10N 2 + PhSO 2NBrNa + H 2O + PhSO 2NH 2 +Na +Br ...( 2.1)+

-

+ -

Where R=H for piperazine, CH3 for 1-methylpiperazine and -C2H5 for 1-ethyl

piperazine.

66

Product analysis The reaction mixture in the stoichiometric ratio in buffer medium was allowed

to progress for 24 hours at 303K. After completion of the reaction (monitored by TLC), the reaction mixture was neutralized and the products were extracted with ether. The organic products were subjected to spot tests and chromatographic analysis (TLC method). The products were piperazine N-oxide, 1-methylpiperazine N-oxide and 1-ethylpiperazine N-oxide. For example, the GC-MS data for piperazine obtained on a 17A Shimadzu gas chromatograph with LCMS-2010A Shimadzu mass spectrometer showed a molecular ion peak at 102 amu (Fig.2.1) clearly confirming the formation of piperazine N-oxide. The reaction product, benzenesulphonamide (PhSO2NH2), was detected by TLC [10] using light petroleum-chloroform-butan-1-ol (2:2: 1= v/v/v) as the mobile phase and iodine as the detection agent (Rf = 0.88). Results

The kinetics of oxidation of piperazine by BAB was investigated by varying the initial concentrations of the reactants in presence of buffer medium at 303K. Effect of reactants

The rate was first order in [BAB]0, since plots of log [titre value]0 versus time were linear (Table 2.1,Fig. 2.2 r > 0.9989) at fixed [Substrate]0 [Buffer] and temperature. The values of pseudo first order rate constants (k´) were constant for varying [BAB]0 [Table 2.2]. The reaction rate increased with increase in [Substrate]0 (Table 2.3, Fig. 2.3) and a plot of log k´ versus log [Substrate] was linear with unit slope, indicating the first order dependence of the rate on [Substrate]. Effect of pH on the rate

At fixed [BAB]0 and [Substrate]0, the rate of reaction increased with increase in pH (Table 2.4 Fig. 2.4) and a plot of log k´ versus log [H+] was linear ( r = 0.9996 to 0.9988) with a negative fractional slope (-0.707 to -0.745) indicating an inverse fractional order dependence of the rate on [H+]. Effect of halide ions on the rate

Addition of halide ion such as Br- in the form of NaBr (3.0 x 10-4-6.0 x 10-4 mol dm-3) has no influence on the rate of reaction, suggesting that bromine was not involved in the rate equation and other reactants are kept constant (Table 2.5).

67

Effect of benzenesulphonamide on the rate

Addition of reaction product benzenesulphonamide (3.0 x 10-4-7.0 x 10-4 mol dm-3)

had no effect on the rate (Table 2.6), when all other experimental conditions were

kept constant.

Effect of ionic strength on the rate

The effect of ionic strength on the reaction rate was carried out in the presence

of 0.1 mol dm-3 sodium perchlorate when all other experimental conditions were kept

constant. It was noticed that the ionic strength had a negligible effect on the reaction

rate (Table 2.7).

Effect of temperature on the rate

The reaction was studied at different temperatures in the range of 298-313K,

while keeping [BAB]0 and other experimental conditions constant. The rate constants

were presented in (Table 2.8 Fig. 2.5). From the linear Arrhenius plots of log k´

versus 1/T the energy of activation (Ea) was computed and from which other

activation parameters, enthalpy of activation (ΔH≠), entropy of activation (ΔS≠) and

free energy of activation (ΔG≠) were calculated (Table 2.9).

Linear free energy relationship

Plots of log k´ versus σp parameter for the ring substituents of piperazine

(H, CH3 C2H5) with the oxidant are shown in (Table 2.12 Fig. 2.7). The Hammett

correlations [11, 12] were fitted with σp = σ+I + σ -R scale.

Test for free radicals

Tests performed for the presence of free radicals by adding the reaction

mixture to acrylamide solution were negative. The absence of polymerization shows

that free radical species in situ are not formed in the reaction.

68

DISCUSSION AND MECHANISM

Bromamine-B (PhSO2NBrNa) is an analogous to CAT [13] and behaves like a

strong electrolyte in aqueous solutions dissociating as,

PhSO2NBrNa PhSO2NBr- + Na+ …(2.2)

The anion picks up a proton in acid solutions to give the free acid

monobromamine-B [14] PhSO2NHBr

PhSO2NBr- + H+ PhSO2NHBr … (2.3)

(Ionisation constant of acid Ka = 1.12 x 10-5 at 25oC)

The free acid has not been isolated, but conductometric titrations of CAT

with cations have given ample proof [15] for its formation in solution. It undergoes

disproportionation giving rise to benzenesulphonamide (PhSO2NH2) and

dibromamine-B as in equation (2.4)

kd 2PhSO2NHBr PhSO2NH2 + PhSO2NBr2 …(2.4)

k-d

kd = 1.13 x10-2 at 250C

Dibromamine-B and the free acid hydrolyse to give hypobromous acid (HOBr)

Kh PhSO2NBr2 +H2O PhSO2NHBr + HOBr …(2.5)

PhSO2NHBr + H2O PhSO2NH2 + HOBr ...(2.6)

Kh = 4.21 x 10-3 at 250C

Finally HOBr ionizes as

Ka HOBr H+

+ OBr- …(2.7)

Ka = 2.0 x 10-9 at 250C\

In high acid concentrations, HOBr can get protonated to H2OBr+

HOBr + H+ H2O+Br …(2.8)

The possible oxidizing species in acidified BAB solutions are therefore

PhSO2NHBr, PhSO2NBr2, HOBr and BrO- ion. If PhSO2NBr2, were the reactive

69

species, a second order dependence of the rate on [BAB]0 would be expected, which

is contrary to the experimental observations. If HOBr is primarily involved, then a

retardation of the rate by the added PhSO2NH2 is expected, which is not observed.

Hence the possible oxidising species is the free acid, PhSO2NHBr.

Furthermore, ultraviolet spectral measurements have shown that piperazine in

aqueous solutions has a sharp absorption band at 235 nm, while BAB exhibits a peak

around 340 nm, both in the presence of pH 4.0 buffer and water. A mixture of BAB

and piperazine in the absence of buffer shows a λmax around 330 nm. This indicates no

direct reaction between BAB and piperazine and no deprotonation from BAB.

However, piperazine in the presence of pH 4.0 buffer showed a λmax of 380 nm, which

is a larger shift in λmax indicating the formation of intermediate S´ due to

deprotonation of the substrate, piperazine. Based on the preceding discussion the

following Scheme 1 is proposed for the reaction.

K1

S0 S- + H+ (i) fast

(Piperazine)

k2 S- + BAB X + PhSO2NH- (ii) slow

(Oxidant) (complex)

X + H2O Products (iii) fast

(PhSO2NH- + H+ PhSO2NH2)

Scheme 1

70

A detailed mode of oxidation of piperazines by BAB in acidic buffer medium

and structures of intermediates are depicted in Scheme 2.

N

NH

RN

N

_(piperazine S0 ) S

+ H+

( R= H,CH3, C2H5)

Fast

pH.4 Bufferi)

..

R

..

-

Scheme 2. A comman reaction path way for the oxidation of piperazines by BAB in

acidic buffer medium.

N

N

RN

NBr

R

..

-ii) + + PhSO2NHBr PhSO2NH

-

(BAB)

Slow

N

NBr

RN

Br

R

N OH

H

N

N

R

OH

+ H2O+

-HBr

..iii)

(Piperazine N- oxide)

PhSO2NH-iv) + H+ PhSO2NH2

71

From the slow step of scheme 1,

Rate = k2 [S-] [BAB] ...(2.9)

S0 = S HK

...(2.10)

[S]t = [S0] + [S ] ... (2.11)

Substitute of eqs. (2.10) in (2.11) leads to eqn. (2.13)

[S]t = S H

Ks S H K

K ... (2.12)

s K SH K

… (2.13)

By substituting for S from eq. (2.13) in eq. (2.9), one gets

rate = K S BABH K

…(2.14)

The rate law (eq. 2.14) obtained from Scheme 1 is in good agreement with the

experimental results, where a first order dependence each on [BAB]0 and [Substrate]0

and an inverse fractional order on [H+] were observed.

Since, rate = k´ [BAB], eq. (2.14) can be transformed as,

k′ K SH K

...(2.15)

′HK S

S

…(2.16)

Based on eq. (2.16), plots of 1/k´ versus [H+] at constant [BAB]0, [Substrate]0

and temperature have been found to be linear (Fig. 2.6 : r > 0.9988) for all

piperazines. The deprotonation constants (K1) and protonation constants (KP) of the

substrate and the reaction constant (k2) were calculated from the slope and intercept of

these plots for the standard runs with [BAB]0 = 5.0 x 10-4 mol dm-3,

[Substrate]0 = 1.0 x 10-2 mol dm-3, [H+] = 1.0 x 10-4 mol dm-3 at 303K. Further the

values of protonation constant of the substrate (KP = 1/K1) were also determined.

These values are presented in Table 2.11.

72

Linear free energy relationship.

Structural modification of a reactant molecule may influence the rate or

equilibrium constant of a reaction through inductive, polar, steric and resonance

effects, which can be used to probe into the reaction mechanism. Out of a number of

empherical models proposed in describing the relationship between structure and

reactivity, the most successful and extensively investigated is the linear free energy

relationship [16] with Hammett equation as the most prominent example. Hammett

treatment describes the substituent effects on the rate and equilibria of aromatic

molecules. In the present system, structure reactivity relationship is ascertained by

utilizing different groups (R = H, CH3, C2H5) at position one on the nitrogen atom of

the piperazine ring and tested to fit the results into Hammett equation [17]. The

Hammett plot of log k´ versus σ (Fig. 2.7 Table 2.12) is reasonably linear

(r = 0.9251). From the plot, the value of the reaction constant ρ is found to be -0.75

signifying that the electron releasing groups in the piperazine ring enhance the rate.

The positive inductive effect of the substituent increases the electron density on

nitrogen of piperazine and subsequently the lone pair of electrons of nitrogen of

piperazine easily attacks the electrophilic bromine of the reactive oxidizing species to

form N-bromopiperazine as the transition state (Scheme 2). Furthermore, the positive

inductive effect of the substituent in the present system increases in the order,

H<CH3<C2H5, justifying the observed reactivity trend of piperazine

<1-methylpiperazine 1-ethylpiperazine for piperazines oxidations.

Isokinetic Relationship

The largest activation energy for the slowest reaction (Table 2.9) indicates that

the reaction is enthalpy controlled, within the reaction series. The variation in the rate

may be caused by changes in either the enthalpy or entropy of activation or both,

among the recognized categories. Rate changes caused by changes in both enthalpy

and entropy of activation quantities in a parallel fashion represent one of the

important categories. In this class, enthalpy and entropy of activation are correlated by

linear relationship ΔH≠ = ΔH≠0 + βΔS≠, which is the isokinetic relationship and β is

the isokinetic temperature. When the experimental temperature T < β, the reaction

rate is controlled mainly by the enthalpy change. In the present case of the piperazines

oxidations, the two activation parameters are linearly related as shown by plotting

73

ΔH≠ versus -ΔS≠ (Fig. 2.8 r = 0.9861). From the slope, the value of isokinetic

temperature (β) computed is found to be 393K. This is further verified by employing

the Exner [18] criterion with a plot of log k´298K versus log k´308K which is linear

(Fig.2.9, r = 0.9990). From the Exner slope β was found to be 383K. The calculated

value of β is higher than the experimental temperature of 303K, Which suggests that

the reaction is enthalpy controlled. The existence of isokinetic relationship is of

significance and is a very valuable tool to the mechanistic chemist when used as

supportive evidence along with other types of data. The large negative value of ΔS≠

indicates a more ordered activated complex and the near constancy of ΔG≠ shows an

identical mechanistic pathway in the oxidation of all the three piperazines studied.

Furthermore, the independent nature of the rate towards the addition of

benzenesulphonamide, halide ion and neutral salts substantiates the proposed

mechanism and the rate law derived.

74

TABLE 2.1

Effect of varying [BAB] on the rate of oxidation of Piperazine, 1-Methylpiperazine, 1-Ethylpiperazine (Representative run)

[Substrates]0 = 1.0 × 10-2 mol dm-3; [BAB] = 5.0 × 10-4 mol dm-3 Buffer pH = 4.0; µ = 0.1 mol dm-3; T = 303K.

Plot of log [titre] versus time (FIG.2.2) k´ = 2.251 × 10-4(sec-1) k´ = 7.67 × 10-4(sec-1) k´ = 9.67 × 10-4(sec-1) r = 0.9980 r = 0.9997 r = 0.9989

PZ MPZ EPZ Time (min)

Titre value (ml) log [titre] Time

(min) Titre value

(ml) log [titre] Time (min)

Titre value (ml) log [titre ]

0 10 20 30 40 50 60 70 80 90 100 110

22.0 19.0 16.8 15.0 13.0 11.0 10.0 9.0 8.3 6.5 6.0 5.5

1.34 1.27 1.22 1.17 1.11 1.04 1.0 0.95 0.91 0.81 0.77 0.74

0 5 10 15 20 25 30 35 40

22.0 17.8 14.5 11.8 9.2 7.6 6.2 5.1 4.1

1.34 1.25 1.16 1.07 0.96 0.88 0.79 0.70 0.61

0 5 10 15 20 25 30

19.5 12.2 8.8 6.5 5.5 4.7 3.8

1.29 1.08 0.94 0.81 0.74 0.67 0.59

75

TABLE 2.2

Effect of varying [BAB] on the rate of reaction

[Substrates]0 = 1.0 × 10-2 mol dm-3; Buffer pH= 4.0; µ= 0.1 mol dm-3; T= 303K.

[BAB] ×104 (mol dm-3) k´ × 104(sec-1)

PZ MPZ EPZ

3.0

4.0

5.0

6.0

7.0

2.23

2.23

2.27

2.17

2.40

7.66

7.31

7.67

7.48

7.50

9.10

9.50

9.50

9.40

9.31

76

TABLE 2.3

Effect of varying [Substrates] on the rate of reaction

[BAB] = 5.0 × 10-4 mol dm-3; Buffer pH = 4.0; µ = 0.1 mol dm-3; T = 303K.

Plot of log k´ versus log [Subs] (FIG.2.3) r = 0.9980 r = 0.9997 r = 0.9989 order = 1.0 order = 1.0 order = 1.0

[Subs]0×103

(mol dm-3)

3+log

[Subs]

PZ MPZ EPZ

k´ × 104(sec1) 4+log k´ k´ × 104(sec-1) 4+log k´ k´ × 104(sec-1) 4+log k´

5.0

7.0

10.0

12.0

15.0

20.0

0.6989

0.8450

1.0000

1.0791

1.1760

1.3010

1.12

1.55

2.25

2.63

3.38

4.56

0.05

0.19

0.35

0.41

0.51

0.65

4.12

5.52

7.67

9.21

11.8

16.7

0.61

0.74

0.88

0.96

1.08

1.22

4.80

6.61

9.55

10.7

13.9

18.2

0.67

0.80

0.98

1.03

1.16

1.26

77

TABLE 2.4

Effect of varying pH on the rate of reaction

[Substrates]0 = 1.0 × 10-2 mol dm-3; [BAB] = 5.0 × 10-4 mol dm-3;

µ = 0.1 mol dm-3; T = 303K.

Plot of log k´ versus log [H+] (FIG.2.4)

r = 0.9996 r = 0.9936 r = 0.9988 order = - 0.717 order = - 0.66 order = - 0.745

pH [H+]×105 5+log [H+] PZ MPZ EPZ

k´ × 104(sec-1) 4+log k´ k´×104( sec-1) 4+log k´ k´×104( sec-1) 4+log k´

3.6

3.8

4.0

4.2

4.4

4.6

25.11

15.85

10.00

6.305

3.981

2.511

1.399

1.200

1.000

0.799

0.600

0.399

1.16

1.58

2.25

3.01

4.26

6.11

0.61

0.19

0.35

0.47

0.62

0.78

4.10

5.42

7.67

11.48

13.48

18.19

0.61

0.73

0.84

1.05

1.12

1.26

4.46

6.60

9.60

12.6

17.7

25.8

0.65

0.81

0.98

1.10

1.25

1.41

78

TABLE 2.5

Effect of varying bromide ion on the rate in the form of NaBr

[Substrates]0 = 1.0 × 10-2 mol dm-3; [BAB] = 5.0 × 10-4 mol dm-3;

Buffer pH = 4.0; µ = 0.1 mol dm-3; T = 303K.

[NaBr] × 104

(mol dm-3)

k´ × 104(sec-1)

PZ MPZ EPZ

3.0

4.0

5.0

7.0

10.0

2.16

2.25

2.20

2.17

2.20

7.53

7.67

7.03

7.00

7.10

9.40

9.22

9.51

9.60

9.30

79

TABLE 2.6

Effect of varying benzenesulphonamide ion on the rate of reaction

[Substrates]0 = 1.0 × 10-2 mol dm-3; [BAB] = 5.0 × 10-4 mol dm-3;

Buffer pH = 4.0; µ = 0.1 mol dm-3; T = 303K.

[BSA] × 104

(mol dm-3)

k´ × 104 (sec-1)

PZ MPZ EPZ

3.0

4.0

5.0

6.0

7.0

2.10

2.21

2.30

2.08

2.20

7.53

7.40

7.53

7.53

7.35

9.30

9.25

9.51

9.22

9.50

80

TABLE 2.7

Effect of varying ionic strength on the rate of reaction

[Substrates]0 = 1.0 × 10-2 mol dm-3; [BAB] = 5.0 × 10-4 mol dm-3;

Buffer pH = 4.0; T = 303K.

[NaClO4]

(mol dm-3)

k´ × 104 (sec-1)

PZ MPZ EPZ

0.05

0.06

0.07

0.08

0.10

2.25

2.10

2.30

2.20

2.15

7.45

7.66

7.58

7.50

7.49

9.40

9.50

9.55

9.61

9.38

81

TABLE 2.8

Effect of varying temperature on the rate of reaction

[Substrates]0 = 1.0 × 10-2 mol dm-3; [BAB] = 5.0 × 10-4 mol dm-3;

Buffer pH = 4.0; µ = 0.1 mol dm-3;

Temperature

(K)

103/T

(K-1 )

k´ × 104 (sec-1)

PZ MPZ EPZ

298

303

308

313

3.355

3.300

3.246

3.194

1.46

2.25

3.66

5.61

4.89

7.67

10.71

16.60

6.92

9.67

13.58

20.00

Plot of log k´ versus 1/T (FIG.2.5) r = 0.9996 r = 0.9982 r = 0.9989 Slope = - 3650.0 Slope = -3228.7 Slope = -3228.7

82

TABLE 2.9

Activation parameters for the oxidation of piperazines by BAB in acid buffer (pH 4.0) medium

Ea ∆H≠ ∆S≠ ∆G≠

Substrate ( kJ mol-1) ( kJ mol-1) (JK-1 mol-1) (kJ mol-1)

Piperazine (PZ) 69.93 67.38 - 95.52 95.65

1-Methyl Piperazine (MPZ) 61.84 59.30 - 109.44 92.74

1-Ethyl Piperazine (EPZ) 55.23 52.69 - 129.0 92.10

83

TABLE 2.10

Plot of 1/ k´ versus [H+]

[Substrates]0 = 1.0 × 10-2 mol dm-3; [BAB] = 5.0 × 10-4 mol dm-3;

µ = 0.1 mol dm-3; T = 303K.

Plot of log1/ k´ versus [H+] (FIG.2.6) r = 0.9951, 0.9945, 0.9988

pH [H+]× 105

(M)

k´ × 104( sec-1)

PZ 1/ k´ MPZ 1/ k´ EPZ 1/ k´

3.6

3.8

4.0

4.2

4.4

4.6

25.11

15.85

10.00

6.305

3.981

2.510

1.16

1.58

2.25

3.01

4.26

6.11

8603.0

6313.1

4444.4

3312.3

2344.6

1636.1

4.10

5.42

7.67

11.48

13.48

18.19

2439.0

1845.0

1303.7

871.0

741.8

549.8

4.46

6.60

9.60

12.6

17.7

25.8

2242

1515

1041

793.6

564.9

387.5

84

TABLE 2.11

Values of protonation and deprotonation constants for the rate of reaction

Substrate K1x10-5(mol dm-3) KPx104 (dm-3mol -1) k2 (sec-1)

PZ MPZ EPZ

2.25 5.00 5.50

4.44 1.93 1.81

0.13 0.23 0.25

TABLE 2.12

Plot of log k´ versus substituent (H, CH3, C2H5)

Substrate k´ × 104 (sec-1) 4+log k´ ρ

PZ 2.25 0.3523 0

MPZ 7.67 0.8847 - 0.41

EPZ 9.55 0.9800 - 0.83

Plot of log k´ versus substituents (FIG.2.7) r = 0.9251 ρ = - 0.75

85

FIG. 2.1 GC-Mass spectrum of piperazine-N-oxide with its molecular ion peak

at 102 amu

86

0 20 40 60 80 100 1200.5

0.6

0.7

0.8

0.9

1.0

1.1

1.2

1.3

1.4

Piperazine 1-Methyl piperazine 1-Ethyl piperazine

log

[Titr

e va

lue]

Time in (min)FIG. 2.2 Plot of log [Titre value] versus time

0.7 0.8 0.9 1.0 1.1 1.2 1.30.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

1.1

1.2

1.3 Piperazine 1-methyl piperazine 1-ethyl piperazine

4+lo

g k'

log [substrate]FIG.2.3 Plot of log k' versus log [substrate]

87

0.4 0.6 0.8 1.0 1.2 1.40.0

0.10.2

0.3

0.4

0.50.6

0.7

0.8

0.9

1.0

1.1

1.2

1.31.4

1.5

Piperazine 1-methyl piperazine 1- ehyl piperazine

4+lo

g k'

5+log [H+]

FIG.2.4 Plot of log k' versus [H+]

3.18 3.20 3.22 3.24 3.26 3.28 3.30 3.32 3.34 3.360.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

1.1

1.2

1.3

1.4 Piperazine 1-methyl piperazine 1-ethyl piperazine

4+lo

g k'

1/T (K-1)FIG.2.5 Plot of log k' versus 1/T

88

0 5 10 15 20 250

1000

2000

3000

4000

5000

6000

7000

8000

9000 Piperazine 1-methyl piperazine 1-ethyl piperazine

1/k'

(s-1)

[H+] x 10-5 (M)

FIG.2.6 Plot of 1/k' versus [H+]

-0.8 -0.6 -0.4 -0.2 0.00.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

4+lo

g k'

σ FIG.2.7 Plot of σ versus log k'

89

-130 -125 -120 -115 -110 -105 -100 -95 -90

52

54

56

58

60

62

64

66

68

?

Iso kinetic temp.β =393Κ

ΔH#

-ΔS#

FIG.2.8 Plot of ΔH# versus ΔS#

0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.90.5

0.6

0.7

0.8

0.9

1.0

1.1

1.2

Exner plot β = 384Κ

4+lo

g k'

(308

K)

4+log k'(298K)FIG.2.9 Plot of log k'(308K) versus log k'(298K)

90

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