Indian JownaJ of Cherrustry Vol. 38B, March 1999, pp. 337-342

Effect of solvents on the kinetics and mechanism of the acidic and alkaline hydrolysis of hydroxamic acids

Kallol K Ghosh·, Kishore K Krishnani & Sharmistha Ghosh

School of Studies in Chemistry, Pt. Ravishankar Shukla University, Raipur, 492 010, India

Received 23 February 1998; accepted (revised) 29 January 1999

The acid catalyzed hydrolysis of N-phenylbenzohydroxamic acid (PBHA) C6HSC(=O)N(OH)C6HS has been studied in aq. dioxane, acetone, dimethylsulphoxide, dimethylformamide, methanol, ethanol and 2-propanol mixtures. Dioxane and methanol have a rate enhancing effect but DMF, acetone, ethanol and 2-propanol exert a rate decreasing effect. In DMSO an increase is followed by a decrease i.e. a rate maximum is observed. An attempt has also been made to study the alkaline hydrolysis of PBHA and two of its derivatives (X-C6H4C(=O)N(OH)C6Hs; X=4-N02, 4-CI) in aq . dioxane. In all case the pseudo first order rate constant increase with increasing dioxane content. The activation parameters t.Ht, t.st and t.GHt, have been calculated. An attempt has been made to correlate rate data for acidic hydrolysis in terms of solvatochromic parameters and linear free energy relationships.

N-phenylbenzohydroxamic acid (PBHA), has extensive analytical applications. We have examined the acidic! and alkaline2 hydrolysis of N-phenyl­benzohydroxamic acid. The aim of this present communication is to extend the knowledge about the kinetic solvent effects with special regard to the mechanism of hydrolysis reaction. However, extensive studies of solvent effects on the acid and base catalysed. hydrolysis of hydroxamic acids have not been reported so far. Solvents have been found to play an important role in elucidating the reaction mechanism3

-7

. The rate of an elementary chemical reaction may change by orders of magnitude when the solvent IS changed. Many theoretical and experimental works have been published8

-1!

concerned with solvent effect and chemical reactivity, yet they are still not completely understood. Quantitative correlation between rate constant and different solvent parameters is still an elusive exercise. The present investigation is, therefore, dealing with solvent effects by employing a wide variety of solvents, i.e., dioxane, acetone (slightly polar basic), DMSO and DMF (polar aprotic and MeOH, EtOH and 2-PrOH (Protic). Recently Marcus l2 developed mathematical formulation dealing with properties ' such as polarity, hydrogen bonding abilities for use in linear solvation energy relationships. Attempts have b~en made to correlate variations in reaction rate with solvatochromic parameters, u.. 13, 1t* using multiple regression analysis.

Materials and Methods N-phenylbenzohydroxamic acid and other para

substituted hydroxamic acids were prepared by the literature procedure! 3 and purity was checked by elemental analysis, mp, UV, NMR, IR and mass spectral data. Concentrated AnalaR hydrochloric acid was standardised against alkali , dioxane (Merck, GR), acetone (Pfizer, certified reagent), DMSO (Merck, GR), DMF (Merck, GR), methanol (BDH, AnaIR), ethanol (Merck, GR) and 2-propanol (BDH LR) were used as such. Kinetic measurements were made by the spectrophotometric method reported previously'4 employing a Systronics UV -VIS 108 spectrophoto­meter set at 520 nm. Pseudo-first order rate constants were obtained from the slope of the appropriate graph with numerical values computed by the method of least squares. Activation parameters calculations were carried out on a WIPRO ACERENTRA 500 computer under MS DOS.

Results and Discussion

Acidic hydrolysis The rate of the acid hydrolysis of PBHA has been

measured in each of these solvents under varying compositions (10 to' 70% v/v) at 45-65°C. The results are presented in table f. - The concentration of catalysing acid HCI was 2.9 AI and PBHA was around 7x I 0-3 M The accepted mechanism for the acid catalysed hydrolysis of PBHA is represented in Scheme I. The reaction followed pseudo-first order kinetics:

338 INDIAN J CHEM, SEC B, MARCH 1999

Table 1-Pseudo first order rate constants for the acid catalyzed hydrolysis of PBHA in d.ifferent binary aqueous mixtures

o 10 20 30 40 50 60 65 70

o 10 20 30 40 50 60 70

Path A

1.92 2.39 2.72 2.80 2.87 3.01 3.51

4.87

1.92 1.90

1.40

1.26

A = Acidic Hydrolysis

B = Alkaline Hydrolysis

4.94 5.53 5.75 6.15 6.48 6.88 7.41 9.28

11.7

Acetone

4.94 4.64 4.02 3.50 3.22 3.07 2.90 2.80

11.4 11.5 12.3 13.0 14.4 15.5 17.8

28.6

11.35 10.9

7.76

6.36

Scheme I

1.92 2.25 2.37 2.31 2.24 2.16

1.92 1.94

1.23

0.98

4.94 5.40 5.74 5.54 5.38 5.28 4.25

3.17

2-PrOH

4.94 4.33 3.57 2.99 2.47 2.16 1.92 1.79

11.35 12.3 13.0

12.61 12.40 12.10

11.35 11.62

7.69

6.00

+ CsHsCOOH + CsHsNH2 -OH

-d [PBI-IA]/dt=k[PBHA] [W]=k", [PBHA] ... (I)

The order of reaction with respect to catalytic acid and substrate has been established previouslyl4 for the conditions employed in this study.

M o

1.92 2.30

2.45

2.92

1.92 1.45 1.21 0.99 0.79

4.94 5.30 5.41 5.62 5.70 6.13 7.29 8.29 10.4

DMF

4.94 3.63 3.02 2.33

1.82

1.65

• Dioxane 12 .0 "DMSO

10.0

8.0

A M.OH .EtOH GAc.ton. 02' Pr OH ODMF

0.1

11.35 12.72

13.68

15.44

11.35 8.75 7.39 5.59 4.37 4.37

0.2

1.92 2. 12

1.83

1.43 1.42

0.3

x

55°C EtOH

4.94 4.75 4.40 4.02 3.70 3.45 3.41

3.57

0.4 0. 5

11.35 11.75

10.05

7.90 7.95

The results listed in Table I .show that the rate constant of the hydrolysis reaction IS sensitive to solvent composition. The observed changes in the rate constants k", with solvent composition (mole fraction) for the reacti0l1 under study are shown in Figure 1. In dioxane and MeOH the rate constants increase with increasing solvent composition . In water-DMSO mixture the rate constants increase with Increasll1g DMSO composition upto a DMSO mole fraction of about 0.06; then they decrease. In DMF, acetone, EtOH and 2-PrOH the rate constants decrease with

Figure I - Variation of rat..: constan t with mole fraction of so lvents for the acidi c hydro lysi s of PBII I\.

GHOSH et al.: ACIDIC & ALKALINE HYDROLYSIS OF HYDROXAMIC ACIDS 339

the increase of their percentage composition in binary aqueous mixtures. The relative catalytic activity of J-t is dictated by the relative solvation of J-t. The more solvated the J-t, the less effective it is as a catalyst for the hydrolysis reaction. The J-t becomes a more active catalyst with increasing composition of dioxane and DMSO as it becomes increasingly less stabilised due to the decreased basicity of the solvents.

It would appear that there is one factor Of solvent property that can cause the rate increase with mole fraction of cosolvent and another property that cause it do decrease. Also, Figure 1 showed that the rate decreases from MeOH to EtOH from 2-PrOH, the three protic solvents investigated. For the aprotic solvents the rate also decreases on going from dioxane to DMSO to acetone to DMF.

The interpretation of kinetic solvent effect on reaction rates is difficult and in general is dominated more by exception than rules. How a particular solvent will effect each step is hard to explain and what is experimentally observed is the net effect. No simple theory appears adequate to explain the effects observed. The first problem is to associate the specific properties of these cosolvents to factors that affect the rate of hydrolysis. The effect of solvent on reaction rate can be rationalized in terms of dielectric constant, water structure behaviour and acidity-basicity parameters. In the present work, no correlation was found between dielectric constant and the rate constant. The rates of hydrolysis in DMF, acetone, ethanol, and 2-PrOH are found to increase with an increase in dielectrk constant. This can be explained in terms of the fact that the activated complexes are much more polar than the reactants. So their formation is encouraged by media of high D. The

reaction in other solvents i.e. dioxane and DMSO shows anomalous results.

Certain properties l 5 that relate to the electron pair donation and acceptance abilities of solvents are also of great importance in kinetics. Of the aprotic solvents, DMSO (29.8) as the largest donor number followed closely by DMF (26.6), acetone (17) and dioxane (14.8).

Although DMF is polar aprotic solvent like DMSO but the rate decreases with increasing proportion of DMF in the mixture. The observed rate increasing effect is possibly indicative of the effect of the possible stable hydrates of DMF imparting more proticity, fr, to the H-bonded intercomponent complex. The factor is bound to decrease the rate as the H30+ concentration is decreased.

The behaviour of binary mixtures of simple alcohols homo logs cause the building u£ to the structure of water to be enhanced I .17. The hydrocarbon groups in the alcohols provide sites for the build up to structure around the alcohol molecule. The peculiar structural features of aq. alcohol solutions produce remarkable effects on the kinetics of reactions. The apparent hydration numbers were found to decrease with increasing concentration of alcohol. The larger the non-polar groups in the alcohols, the greater the extent of hydration decreases.

In MeOH-water mixture, the build-up of structure of water around the alcohol molecule does not occur since the methanol shows about 1.1 association with water l8 that does not change very much with concentration. Moreover, the interaction between the proton and the water molecule in the mixture should be stronger than in pure water, since the inductive effect of the methyl group makes the methanol molecule more basic and less acidic than the water molecules. The increasing affinity of water to the proton and the non-association of water molecules in methanol leads to the enhancement of the hydrolysis continuously by the successive addition of methanol.

The results obtained in EtOH and 2-PrOH depends upon different factors . Both alcohols act as strong hydrogen bond donor and acceptor. A water molecule involved in hydrogen bond formation with alcohol molecule is less nucleophilic than that involved in hydrogen bond formation with another water molecule. This will appear In the expected bimolecular mechanism.

Linear free energy relationships Several parameters convey to describe the chemical

properties of solvent mixtures. Linear free energy relationships or linear solvation energy relationships relate such properties to diverse process in solution . The quantity that describes the intensity of such a process (XYZ) depends on more than one solvent property. Of the many expressions that have been proposed for the LSERs one that was found to be very successful is the Kamlet-Taft equation l9

. . . XYZ = XYZo + au + b13+s1t* + ... . . .. (2)

For rate processes, this expression can be written as

log kljl = Ao + au + b13 + S1t* . .. (3)

where Ao, a, band s are solvent independent coefficients characteristic of the process, kljl ic; rate constant and u, 13, 1t* are the solvatochromic proper-

340 INDIAN J CHEM, SEC B, MARCH 1999

ties. In this equation a represents the hydrogen bond donation ability (HBD) of the solvent ~ is its hydrogen bond acceptance (HBA), and 1t* describes a combination of properties, the polarity and polarizability of the solvents. The vaslues of a, ~ and 1t* are available for binary solvent mixtures l2b

. It may be mentioned here that out of the seven compositions (10-70% v/v), we have applied LSER, for 10-70% (v/v) composition. It was found that only in 70% (v/v) composition multiple linear regression gives better correlation. In dilute regions the properties are not very different. The results of correlation analysis in terms of Eqns 4-7, a triparametric equation involving a, 13, 1t*, a biparametric equation involving (a, 1t* and i31t*) and separately with 13 are given below:

log k\jl = - 6.23 + 1.71a - 0.92~ + 3.481t* R2 =0.916,sd=0.13,n=6 . .. (4)

log k\jl = - 6.80 + 1.60a + 3.481[* R2 = 0.794, sd = 0.18, n = 6 · .. (5)

log k = - 1.73 - 1.80 ~ + 0.57 1t* R2 = 0.126, Sd = 0.37, n = 6 · .. (6)

log·k = - 2.70 + 0.5013 R2 = 0.158, n = 6, SD = 0.33 · .. (7)

Kamlet's triparametric equation explains ca. 91.6% of the effect of solvent on the hydrolysis. The major contribution is of solvent polarity, which sums up all the specific and non-specific interactions of the media with initial and transition states. Both ~ and a play relatively minor. roles.

Alkaline hydrolysis Pseudo-first order conditions (in large excess of

OIr) were used in all the kinetics. It is evident from Table II that for all the three hydroxamic ac ids the observed first order rate constant gradual ly increases with increasing dioxane content at all the three

temperatures. The accepted mechanism of alkaline hydrolysis of hydroxamic acids is represented in Scheme I. The main factors which cause changes in the rate with increasing dioxane content are the decreasing availability of the protic solvating species and the decreasing dielectric constant of the medium (Figure 2). When dioxane is added to an aq. solution, Jioxane-water hydrogen-bonded complexes are formed20

. However, dioxane is a hydrogen-bond acceptor of strength comparable only to water.

Activation parameters The temperature dependence of the rate constants

of the acidic and alkaline hydrolysis was analysed by a least square procedure using a computer program (Eyring equation) which produces values for ~Ht,

[AJ

0·0 0.02 ~4 0.06 _ 0.08 <>--0-0 P B HA II ....... ~- CI PBHA t.-b-IJ. ~-NO 2 PBHA

-u ~

~ ~

-1 .4

- 1.8

- £.0

O.O~ 0.06 0 .08 1.00

1/0 Figure 2 - Plots of log k., vs I/O for the alkali ne hyd rolysis of hydroxamic acids.

Table II - Pseudo first order rate constants for the alkaline hydrolysis of PBHA, p-CIPBHA and p-NOz PBHA in aqueous dioxane mixtures

Dioxane PBHA p-CIPBHA p-N02PBHA O/OVN ... 55°C 65°C 75°C 55°C 65°C 75°C 55°C 65°C 75°C

10 2.58 6.54 17.9 2.76 7.68 21.5 4.26 11.3 30.5 20 3.36 9.42 23.2 4.14 11.7 30.6 5.04 13.4 35.2 30 4.56 13.4 30.7 5.15 13.5 35 .9 7.44 20.3 50.4 40 6.72 18.7 41.2 8.16 20.3 53.5 9.54 26.6 64 .2 50 11.9 26.8 70.8 12.3 26.9 74.4 12.5 34 .1 81.0 60 18.1 37.9 95.4 18.3 39.2 105.0 18.4 42.1 105.6 70 25 .7 52.7 119.4 22.9 53.5 125.4 24 .9 59.2 138.6 80 33.0 90.8 124.S 40.9 94.2 41.8 96.6

Solvents %VN

0 10 20 30 40 SO 60

o 10 20 30 40 50

GHOSH et al. : ACIDIC & ALKALINE HYDROLYSIS OF HYDROXAMIC ACIDS

Table 111- Activation parameters for the acid hydrolysis of PBHA in different aqueous solvent mixtures'

~Hl

73 .9 67.7 64 .8 66.0 69.5 70.7 69.9

73.9 75.5

73.9 69 .7

Dioxane

-99 -117 -125 -121 -110 -106 -107

Me2CO

- 99 - 95

- 102 - 11 5

~Gl

103.3 102.5

0.0 102.0 102.2 102.1

103.3 103 .6

104.3 104.2

~Ht ~Sl

DMSO

73.9 -99 73.5 -100 73 .5 -99 73 .2 -100 73 .9 -99 74 .3 - 97

2-PrOH

73 .9 -99 77.3 - 89

79.2 - 87

78.1 - 93

~Gl ~Hl ~Sl ~Gt L'.HI ~Sl

MeOH EtOH

103 .0 73.9 -99 103 .3 73 .9 -99 103 .0 73 -99 103.0 73 .8 -99 102.9 102.9 73 .5 - 101 103.0 74.1 -97 102.9 103 .1 73.9 - 102

71.9 -102 102.2 74.4 - 101

DMF

103.0 73.9 -99 103 .3 103.7 76.8 -93 104.3

78.3 -90 104.9 104.9 74 .9 - 102 105.2

73 .7 - 108 105.7 105.6

341

~G:

103.3 103 .2

103 .6

104.2 - 104.2

. , HCI] =2.9M, ~Ht and ~G l values in kJmor l and ~st values in JK- I mol - I.

Table IV - Activation parameters for the alkaline hydrolysis of PBHA p-CIPBHA and p-N02PBHA in different compositions of aqueous dioxane mixtures'

Dioxane Corr. Curr.

% VN L'. 111 ~Sl ~Gl Coerf. Ml t ~Sl ~G: Coe rf.

PBHA p-CI PBHA

10 89.4 - S7 106.4 0.999 94.8 - 40 106.7 0.999 20 89.1 - S6 105.6 0.999 92.4 - 44 105.4 1.000 30 88.1 - 56 104.7 0.998 89.4 - 52 104 .6 0.999 40 83 .6 - 67 103.4 0.998 86.6 - 56 103.3 0.999 50 81.8 -68 101.9 0.997 82.7 - 65 101.9 0.996 60 76.1 - 82 100.4 0.997 80.2 -69 100.7 0.996 70 70.3 - 97 98.9 0.998 77.9 - 74 99.9 0.999 80 60.9 - 122 97.1 0.959

p-N02PBHA

10 90.8 -49 IOS .2 0.999 20 89.7 - SI 104.7 0.999 30 88.2 -S2 103 .6 0.999 40 88.0 -SO 102.9 0.999 SO 86.2 -S4 102.1 0.999 60 80.3 -69 100.7 0.999 70 78.9 -71 99.8 0.999

~st, ~Gt, the enthalpy, enthropy and free energy of activation . The results are listed in Tables III and IV.

manner. In dioxane, methanol , acetone and DM F ~H t decreased with increasing mole fraction of organic solvent, ~Ht become more negative, the overall effect resulting in little variation in ~Gt, The decreasing values of ~st point to ordered transition state structure in accord with charge development and consequent eletrostriction of solvent molecules. The

Acidic hydrolysis It is evident from the results in Tables III and IV

that no definite trends have been observed , The ~Ht and ~st values vary in a more or less compensating

342 INDIAN J CHEM, SEC B, MARCH 1999

variatIOn of ~st and SHt with increasing molar composition of co-solvent is not linear. This non­linear dependence of activation of spec ific solvation taking place in the medium and hence a non-random distribution of the solvent molecules. The negative entropies of activation in all so lvent mixtures indicates that the polar transition state is preferentially solvated by water molecules. Thus a reorganization of solvent molecules occurs on going from the initial state to the transition state .

Alkaline hydrolysis The thermodynamic parameters ~st , ~Ht , ~Gt

(Table IV) can be conceived of as a measure of the di fference in the total complexity of the transition state as compared to that of the reactant state . Some useful insight with regard to the change in the structural aspects of .the solvents might be obtained from the changes in ~Ht and ~st, which contain important structural contributions. It has been pointed out that the stabilization of the activated complex by the solvent involves restriction of motion of some of the molecules. Solvents having permanent dipole moments will , therefore, be preferentially oriented such that an attractive interaction rather than repu lsion takes place. On the other hand, non-polar solvent.s will be relatively unoriented and hence will have higher entropy of activation. These solvent will, therefore, have a greater loss in entropy as a result of so lvation, and reaction in these solvents will consequently have a large negative entropy of activation ~st, which has large negative values, decreases with increasing dioxane content. The negative values of ~S! point to a transition state that is more ordered than the reactants . In all the cases ~Gt increases sl ightly with increase in dioxane content. The lesser dependence of ~Gt is due to largely to the general linear compensation between the enthalpy and entropy of activation at a given temperature .

Proposed mechanism for alkaline hydrolysis It has been observed that introduction of electron­

attracting group (CI and N02) increases the rate of hydrolysis. The three substrates show almost parallel behav iour. This appears to confirm the same detailed mechanism occurs for all these hydroxamic acids . For systems with c-omparable initial states, e.g. hydroxide anion and hydroxamic acid, a reaction in which protic so lvation is less important would respond more

effectively to an increase in dioxane than those in which protic solvation of the transit ion state is more important. Protic solvation is more Important for transition states which have a localised charge structure, especially where the locali 'ation is an electronegative atoms, than fo r those in which the charge is delocalised. Thus reactions which involve attack by O H- at a carbonyl group, req uire more protic solvation for the ' alkoxide-like' transition state than reactions which proceed by abstraction of a proton by OW, having a delocalised ' enolate-like ' transition state.

Ac~owledgement

The financial support from Departmen t of Science and Technology, New De lhi i gratefully acknowledged. The authors are grateful to Prof. V K Gupta, Head, School of Studies in C hemistry, Pt. Ravishankar Shuk la University, Raipur for providing facilities.

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