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Hydrolysis of Amides: a Kinetic Study of Substituent Effects on the Acidic and Basic Hydrolysis of Aliphatic Amides

Hydrolysis of Amides: a Kinetic Study of Substituent Effects on the Acidic and Basic Hydrolysis of Aliphatic Amides

University of Wollongong Research Online

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1969

Hydrolysis of : a kinetic study of substituent effects on the acidic and basic of aliphatic amides

Grahame Leslie Jackson Wollongong University College

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Recommended Citation Jackson, Grahame Leslie, Hydrolysis of amides: a kinetic study of substituent effects on the acidic and basic hydrolysis of aliphatic amides, Doctor of Philosophy thesis, Department of Chemistry, University of Wollongong, 1969. https://ro.uow.edu.au/theses/1157

Research Online is the open access institutional repository for the University of Wollongong. For further information contact the UOW Library: [email protected] HYDROLYSIS OF AMIDES

A KINETIC STUDY OF SUBSTITUENT EFFECTS ON THE ACIDIC AND BASIC HYDROLYSIS OF ALIPHATIC AMIDES

by

G. L. JACKSON B.Sc.(Hons). A.R.A.C.I.

v-i.

Chemistry Department Wollongong University College UNIVERSITY OF N.S.W.

December 1969 898750 ni

SUMMARY

Kinetic rate constants over a range of temperature, enthalpies of activation and entropies of activation have been measured for the dilute of fourteen aliphatic amides together with similar data for the of thirteen aliphatic amideso

These results, in conjunction with those of previous workers, indicate that the dilute acid hydrolysis of aliphatic amides is governed by a combination of steric and hyperconjugative substituent effects. The reaction series is well correlated by the Taft-type equation

Log k = 1.12 ECs - 0.564(n-3) + log k o Q in which Eg denotes a pure steric substituent parameter and n is the number of alpha-hydrogens in the substituent.

The results obtained for the halogeno-amides indicate that the acid hydrolysis of amides may show a slight sensitivity to polar effects.

The results for the alkaline hydrolysis of a similar series of amides are well correlated by the equation

log k = 1.6 7

1 o e the alkaline hydrolysis is governed by a combination of polar, steric and hyperconjugative substituent effects

The deviant behaviour of* the cyclic alkyl substituent in the above correlations is discussed in terms of the conformational inhibition of hyperconjugative effects in the hydrolysis TABLE OF CONTENTS

Page

OBJECTIVES i

INTRODUCTION 3 A: Kinetic and Thermodynamic Relationships 4 B: Substituent Effects 14 C: Theory of the Taft Equations 21 D: Hydrolysis of Amides 29

EXPERIMENTAL 39 A: Preparation and Purification of Amides 40 B: Kinetic Methods 42 C: Techniques used in the Present Work 47

EXPERIMENTAL RESULTS Volume 2

DISCUSSION 66 A: Discussion of the Results of the 67 Acid Hydrolysis of Amides B: Discussion of the Results of the 96 Basic Hydrolysis of Amides C: Analysis of the Taft Substituent Parameters in Terms of the Hydrolysis 108 of Amides D: Extrathermodynamic Relationships 122

BIBLIOGRAPHY 128

ACKNOWLEDGEMENTS 134

APPENDIX 1 - Computer Programmes 135

APPENDIX 2 - Statistical Tests Employed 149

APPENDIX 3 - Publication involving the Cover Candidate Envelope 1

OBJECTIVES 2

The hydrolysis of amides is a reaction of considerable interest from both a practical and theoretical point of view.

Practically, because amides may be considered as the basic units of protein molecules and a knowledge of their reactivity is clearly of considerable importance. The theoretical interest in the hydrolysis of amides lies in the mechanistic similarity of this reaction to the hydrolysis of , the defining reaction for the Taft'*' family of linear free energy relationships.

A very extensive study of the hydrolysis of aliphatic amides has been made by Bruylants and his various co-workers.

Later work by Bolton and Wilson, 3 9 4 has shown that most of

Bruylants* data on the acidic hydrolysis of amides is in serious error due to an unfortunate choice of catalyst acid.

A re-investigation of this important reaction is therefore justified.

In the present project, the amides used have been carefully selected so as to provide the maximum amount of information on the effects of structural changes on the hydrolysis reaction in both acidic and basic solutions. 3

INTRODUCTION 4

A: KINETIC AND THERMODYNAMIC RELATIONSHIPS

5 The mechanism generally accepted Tor the hydrolysis

of amides in alkaline and dilute acid solution indicates

that the reaction is first order with respect to both the

catalyst and the and thus is of overall second order.

In view of this the kinetic data collected during this

investigation were processed using the standard second

order rate equations described below.

Integrated Rate Equations

Three rate equations are commonly used for the study of

second order two component systemso The relative magnitude

of the initial concentrations of the two components

determines which equation is applicable for a specific set

of kinetic data.

a) Reactant Concentrations Unequal

The stoichiometric equation for the hydrolysis of amides

may be represented as

A + B ■> Products

and the reaction rate by

dc -dc A B (i) dt dt 5 If a and b represent tbe initial molar concentrations of

A and B respectively and x is tbe product concentration at time t tben

C. = a-x and C_, = b-x A B

Substitution for and in equation (l) yields

dx = k(a-x)(b-x) ••••••...... ••••••••(2) dt which on integration, between the limits of t from 0 -- >t and x from 0 — ^ x, by the method of partial fractions, yields

kt = 1 In f b (a-x) \ ...... • • A a-b \ a(b-x) j b) Reactant Concentrations Equal If the initial concentrations of A and B are equal then

equation (2) reduces to

dx = k (a-x) ^ dt

and on integration, between the limits described above, becomes

kt x B a(a-x)

c) Reactant Concentrations Marginally Different

In many cases the initial concentrations of the reactants

differ only by a small amount. Such kinetic data can be processed in two ways;- 6

i. By averaging the initial concentrations of the

reactants and calculating rate constants using

equation i.e. equal concentrations equation.

ii. If the difference in the initial reactant

concentrations is too large to allow accurate

calculations using the "averaging technique",

but too small to justify the use of equation A ,

then a correction procedure derived by Benson^ can

be employed.

For the general reaction

A + B ---> Products

dx = k.A.B...... (3) dt at any time t

B = B - x o

= B - (A - A) o N o 7

= A + B - A o o

= A + A where /\ = B - A i.e. the small difference in the ^ ^ o o initial concentrations of A and B. Substitution in equation (3 ) for B yields 7

dx k. a (a + A. ) dt

k (A' * 4 -)(A’ - - t ) w h e r e A = A + A 2 “1 2 • * • dx = k A dt (4)

Hence dx = k 4 ) dt •*? It ¿\± is small compared with A o then the term in brackets changes only minimally during the reaction, e.g. if

/\A = A o 1 , the term in brackets changes from 0.99 initially . . 4 to O .96 after one half life. It may therefore be considered a constant when integrating and replaced by its mean value over the part of the reaction studied. The mean value

(geometric mean) is

F = 1 - A (5) 4a o 1 x A^1 <£ where A^ 1 is the final value of A 1 measured.

Substitution for F in equation (4) yields / \ 2 dx = k.F. (A j dt V ' which on integration, between the previously described limits, becomes

k.F.t = 1 1 A 1 1 Ao - x A 8 or finally

1 1 k.F . t C

where F has the value defined by equation (5) or, in terms of initial concentrations

2 F = 1 - ^ (2Aq + ^ ) (2Af. + ^ )

With the aid of the above rate equations it was possible to calculate rate constants for reactions in which the kinetics of the reaction were followed by chemical techniques.

Correlation of Physical Properties with Concentration.

For a physical property to be of use for kinetic studies it must vary linearly with concentration. For the reac tion

A + B + C ------> P

where P denotes all the products let A be the value of such a physical property at time t.

Then

where the contribution from the medi^., and m i s A is the contribution from all the products. 9 If a linear variation with concentration is assumed then

^ $ where -0^ is a proportionality constant and

A = r + * c ( c 'x) + ■ ■

Initially, i0e0 at t = o

*o = + + % 8 * ^ ...... ‘>•(6)

The reaction ceases when one reactant is completely

consumed. If we assume that all of A is consumed then,

at t = co

K + *»(*.-*.) * -e-.(Co-4.)+ ...... (7)

From equations (6) and (7 ) it is possible to calculate X - X = -0 - /7 —

and A - A 0 = -e-pX. - -e-fiX -

which on simplification become

^ \ ^ ...... (8)

and ^ ~ \ ~ ..... •••••(9 )

where z\-e- = -e-p - & p - -e-& -

Manipulation of equations (8) and (9 ) produces the following useful relationships

A — A „ * (10) A 00 ~~ A 0 = t o ..... 10

-A«*» ~ >o - __As...... ( n ) ^oo - A A o - x and _____- Ao______B 0 ...... (12)

From equations (10), (11) and (12) tlie integrated rate

equations derived earlier may be correlated with, any physical property of a reaction mixture which varies directly and linearly with concentration.

Equations Required for the Resistance Techniques.

The conductance of a solution is one example of a physical

property which for many substances varies directly with

the concentration of the species producing it. In the

present work it was experimentally simpler to measure the

resistance of the reaction mixture, but since

Resistance od ______1______Conductance

and Conductance cpC Concentration

then Resistance oC ______1______Concentration

The following rate equations were used during the present

study: -

(a) Initial Concentrations Equal

The equation previously derived for second order two

component systems with the initial concentrations equal was 11 kt = x_____ ~"Â (T - x) O X O 7

A - x o

Substitution from equations (lO) and (ll) yields

A t _ A - A / A pq — A i -Aoo A Ao -A*- — AC*0 i . e. k t - A - A A^. ~ A oo In terms of resistance values

- 1 R R. kt = 1 D - 1 R R

(b) Initial Concentrations Unequal

The equation previously described for a second order, two component system with the initial concentrations unequal was

Substitution from equations (ll) and (12) yields

kt / A«. - A 7 R - Ô ( A«, -*.) --f-U-A.) A eo "" A 0 /

/ Aoo — A______Uoo - A,) - (A - Ae) 12 which, in terms of resistance values becomes

( i - 1 kt = 1 In ( Reo R t ' A-B ( i - 1 Ì - A 1 1 - i ) B - v(R o )' i R t R o )/

The rate equations D and E were modified by the use

of a computer subroutine to overcome certain experimental

difficulties encountered during the hydrolysis. The

justification and a detailed description of this subroutine

appears in the Experimental Section - page 62

Thermodynamic Relationships

The theory of absolute reaction rates, as described by

Glasstone, Laidler and Eyring 7 , predicts that during a

reaction the initial reactants are in equilibrium with

the activated complex (transition state) and that the

transition state decomposes at a definite rate. If the

equilibrium constant is represented by K* then, for a

simple reaction path with a transmission co-efficient of

unity,

k = -K' T K* ...... (13) h

where -K" is Boltzmann* s constant

h is Planck*s constant

T is the absolute temperature

and k is the rate constant for the process 1 3 The reduced equilibrium constant K* may also be expressed in terms of* the standard free energy of the process by means of the familiar thermodynamic relationship.

-AG = RTInK where AG° is the standard free energy of activation and

R is the universal gas constant.

Substitution for K* in equation (13) yields

k : h e (15) and since for any isothermal equilibrium process

A G° - - T & £ * equation (15) can be written as

XT n r k = h or as

Ai" n r F

Equation F offers a method of evaluating enthalpies and entropies of activation which is theoretically more g acceptable than the more traditional method involving

the use of the Arrhenius equation. Since it operates directly in terms of the transition state theory the only assumptions it makes are those inherent in that theory. 14 In the present work all thermodynamic parameters were calculated by using equation F i.e. from plots oF

In / k \ against 1 0 For the present series of compounds V T ) T the traditional Arrhenius equation always gave results essentially identical to those obtained by equation F *

B, SUBSTITUENT EFFECTS

© 9 It is well known s that the reactivity oF organic compounds is largely determined by the nature of their

Functional groups. However, a complete understanding oF how substrate and reagent structure aFFects the reactivity oF molecules has yet to be developed. An accumulation oF equilibrium and rate data over the past years has allowed the Formation oF a number oF empirical and semi-empirical relationships which have achieved some measure oF success in correlating structure and reactivity.

BeFore discussing these relationships it will be necessary to outline the possible inFluences oF a substituent upon rate and equilibrium processes. In attempting to correlate structure and reactivity the inFluence oF a substituent can best be divided into three 10 15 categories ; -

(a) inductive or electrostatic

(b) steric

(c) resonance or conjugative

(a) Inductive Effects

The inductive effect is that portion of the electrical

influence of a substituent which is transmitted through

a chain of atoms by polarisation of the bonding electrons

from one atom to the next. This effect Mdies off” quickly

in a carbon chain and is felt for only two or three carbon

atoms - e.g. in chloroacetic acid the electrons in the

C-Cl bond are displaced towards the chlorine. This makes

the methylene carbon atom electron deficient in comparison

with the methyl carbon atom of acetic acid. This causes

the C - 0 bond to be slightly polarised towards the carbon

in chloroacetic acid and classical theory suggests that

this increases the strength of the acid by aiding the

departure of the hydrogen as a proton - i.e. the inductive

effect is primarily a displacement of sigma electrons.

CO l— ChL — CH3 ~ ^ C 0 — H

Chloroacetic Acid Acetic Acid 16 An effect closely related to the inductive effect is the field effect. The term field effect is reserved for that part of the electrical influence of a substituent which is transmitted to the reactive group through space

(including the solvent, if any) in accordance with the laws of classical electrostatics. Separation of these effects has proved difficult 11 and for the purpose of this discussion these effects will be grouped and called

POLAR EFFECTS.

(b) Steric Effects

The steric effect of a substituent is the influence a

substituent has upon a reaction rate due solely to its ability to occupy space, i.e. the actual physical size

of the substituent. In the past ”steric hindrance” has

been used to explain a number of trends in reactivity which can be more convincingly explained electronically?*^*"^

However, a large body of chemical data remains which is

best explained using steric arguments. Steric effects

are most easily visualised if transition state complexes

are considered, e.g. in the basic hydrolysis of aliphatic

esters using the £ ^ 2 mechanism, the carbon atom under 2 3 attack changes from an sp to an sp hybrid state

R R & I <£> \ C = 0 +■ OH ■C— 0 ROH + RCOO R'O''' RO in 17 1 If both. R and R are bulky groups then formation of the transition state requires that they will be "crammed" together more than in the reactant molecule. Thus the transition state is of higher energy and the reaction is sterically hindered. If, on the other hand, formation of the transition state relieves a steric stress in the substrate the reaction will exhibit "steric acceleration”.

(c) Resonance Effects

A resonance effect is one which operates mainly via the

77”-electrons in an unsaturated system and thus is extremely important for reactions involving aromatic compounds. In aliphatic compounds resonance effects, of the type found in aromatic compounds, are usually negligible. However, secondary conjugation effects have been observed in aliphatic compounds and these have been labelled as

"hyperconjugation effects”.13

(d) Hyperconjugation Effects

Baker and Nathan, in their work concerning the interactions of alkyl substituted benzyl bromides with pyridine in acetone 13 , showed that while the alkyl group substituents facilitated the reaction, due to their electron releasing properties, the effect was the reverse of that expected on the basis of general inductive effects, i.e. the reaction decreased in the order methyl ethyl 18 iso* Propyl "> tert.-butyl, whereas the inductive effects

increased in the same order. They concluded that the methyl group permits an additional electron release by a mechanism which diminishes or is unable to function in higher alkyl groups and that in general "when a methyl

group is attached to a conjugated system the duplet of

electrons forming the C-H bond are appreciably less

localised than are those in a similarly placed C-C bond.” 13

This phenomenon became known as the Baker and Nathan Effect

or Hyperconjugation.

14 Taft and Kreevoy have correlated structure and

reactivity for the acidic hydrolysis of twenty-four diethyl

acetals and ketals and have found that the hydrolysis is

governed predominantly by the polar influence of the

substituents. The rate of hydrolysis was found to be

insensitive to the steric influence of the substituents,

but was affected by a perturbation proportional to the number of alpha-hydrogens present in the molecule. The

reaction series was best correlated using an equation of

the type

/?(*/*.)» »'9/* * where the sum of the polar substituent parameters

for the substituents.

/\ /7 is the difference between the total number of alpha-hydrogens in the substituents and the standard member 19 for the series and

h is an empirical constant measuring the facilitating effect of a single alpha^hvdrogen on the reaction rate.

From the results of the hydrolysis Kreevoy and

Taft concluded that:- a) the reaction is governed by a combination of polar and C-H hyperconjugation effects. b) the effects are separate and independent. c) the C-H hyperconjugation effect is proportional to the number of aloha-hydrogens in the system.

A considerable body of evidence has since been 15-17 accumulated to support the conclusions above .

While there is probably no single piece of evidence which cannot be explained in other ways,1^ 1^ most of the data of the type just described can be simply and convincingly explained by assuming ” that a hydrogen atom one atom removed from an unsaturated system lowers the potential energy of the molecule containing it.ft 20 This concept of an "extra" stabilisation caused by hydrogen atoms adjacent to a 77"-electron centre will be referred to in the present discussion as ” -hydrogen bonding”, to distinguish it from the classical concept of "hyperconjugation” as described by Baker and Nathan. In most quantum mechanical treatments of models similar to the above system it is assumed that interactions between non-bonded atoms are negligible. Simple phenomena, such as optical rotation^^’^^ and rotational isomerism^^, which depend upon interactions between non-bonded atoms indicate that this is not the case.

Kreevoy and Eyring 20 , using molecular orbital calculations in which non-bonded atom interactions have been considered, have arrived at the following conclusions in regard to cL-hydrogen bonding:- a) the added stabilisation which -hydrogen bonding produces in a molecule is due to a delocalisation of the electrons of the C-H bonds over the molecule, i.e. the electrons of the C-H bonds can delocalise into the electron system present. b) each C-H bond exerts an independent effect. This is in contrast to classical hyperconjugation in which the methyl or methylene group is required to act as a unit. c) the first -hydrogen will have the largest effect since it can assume the most favoured bonding position.

The second and third gC -hydrogens also exert effects, but due to rotation about the C-C sigma bonds the effect of the alpha-hydrogens is average when more than one is present.

Alpha-hydrogen bonding, as defined above, is almost universal and relates only to the portion of hydrogen 21 bonding which is due to electron delocalisation, but not to the larger portion which seems to be due to simple electrostatic interactions.

C. THEORY OF THE TAFT EQUATIONS

For many reaction series a linear relationship exists between log k for one reaction series A and the corresponding log k for another reaction series B. Since

¿\G = -RT/nk

where ¿\Gc =. the free energy of activation R = universal gas constant

T = the absolute temperature

and k = the rate constant e .g .24 we have in fact a "linear free energy relationship"

The first linear free energy relationship of importance was the Hammett Equation . This equation successfully correlated the effect of meta and para substituents on the reactivity of benzene ring side chains but failed when it attempted correlations of ortho substituted benzoic acid derivatives or any aliphatic reactions where steric effects play an important role. Ingold 10 ’ 28 suggested that the total effect of a substituent could be separated into a 22 1 29-32 steric term and a polar term. Taft ’ followed up

this suggestion and has produced a series of apparently workable relationships which have had some success in quantitatively predicting the influence of substituents

on many reactions.

In essence, Taft assumed that the change in free

energy of activation for a reaction series may be

represented as the sum of polar, steric and resonance

contributions.

x . e. Z\6r = G polar Z\G:steric /SGrresonance

Taft used the hydrolysis of aliphatic esters as a

defining reaction and in particular used the mechanistic

similarity of the acidic and basic hydrolysis of esters

as the basis of his derivation. Examination of Figures

la and lb indicates that the difference between the two

transition states is only two protons.

H / Fig, la: Transition state R C ------complex for the acid R hydrolysis of esters proceeding via the A 2 Hx H AC mechanism.

1 © 0 Fig, lb i Transition state R c 0 \ \ < complex for the basic 0 R hydrolysis of esters H/ proceeding via the B^_,2 mechanism. 2 3 Noting this, Tait made the following assumptions:-

a) since the transition states differ by only two protons,

steric effects of substituents will be similar in acidic

and basic hydrolyses.

b) for common substituents, likely to be encountered in

aliphatic esters, resonance effects will be constant or

negligible throughout the reaction series.

c) the rate of acid catalysed hydrolysis is independent

of the polar effects of the substituent.

The last assumption was difficult to justify by rigorous

argument, but was supported by a large amount of experimental

evidence, e.g. in acidic media ethyl acetate and ethyl

chloroacetate undergo hydrolysis at very similar rates, while in basic media ethyl chloroacetate undergoes hydrolysis

at one hundred times the rate of ethyl acetate 33 •

If, as Taft assumed, the effect of a substituent upon

a substrate is made up of a steric, polar and resonance

contribution, then for a substrate X

- log + log + a G r^ - (z^G p t A G ^ + ZM3^ jj

e a Assumption (b) indicates that Z^G^ ^ ^

i.e. logk - logka + A G s) - ( A G ^ + A G ^ 'jj

Similarly for a second member of the reaction series

logk^- logk^ = m [ ( AGp* *■ AG®’) - ( AG*' + A 6 )] Subtraction and use of the notation 24

a r 8 8 1 A G = A G o — AG etc. f L px r . J produces the relationship

l0^ ) =m[ Sx-cAGP + Sx-oAGi “ Sx-oAV S>-„a Gs ] (i)

Assumption (c) indicates that the acidic hydrolysis IS

insensitive to polar^ effects, ’ i.e. £ X-o A G p ^ o

Assumption (a) indicates that the steric influences of

a substituent are similar in acid and base, i.e.

o^ /\G ^ or AG * x-o s *-o ^

Substitution of these results in (l) gives

0 0 = m ^ - o A G " ...... l^ )u0 - |gi^) **0

The left hand side of (2) was defined by Taft as the "polar

reaction factor" such that

^ = 2^ [ ,09 ^ ~ ] ...... (3)

The constant factor of 1/^248 puts the values on a

similar scale to the Hammett values and thus allows easy

comparison. Substitution of this new substituent parameter

into an analogue of the Hammett Equation produces the

TAFT LINEAR POLAR ENERGY EQUATION ¥c logk - log k B =

Reaction series which, are governed by the polar influences

of substituents only may be expected to be correlated by

this equation and is a reaction parameter indicating

the sensitivity of the reaction series to polar effects.

Reaction series successfully correlated by the Taft Polar

Energy Equation includej-

i) ionisation of aliphatic carboxylic acids

ii) ionisation of ortho substituted benzoic acids, and

iii) the ethanolysis of tertiary alkyl halides by an SN^

mechanism.

If the acidic hydrolyses of two aliphatic esters are

considered then, by a similar process,

AG* Ì - ( AG* y- AG* io^ = m '[ ( K ” K ,X )/ • ( ' **

Rearrangement of this gives

HU!)

i... loggf) = m ' [ A g 'p - S ^ a o ']

as written in the alternate notation.

Since AG ^ 0 for the acidic hydrolysis of two X-o p aliphatic esters (assumption (c)^ then:-

>°g = m ' K - o A G 1 26 Taft defined E = log / k and called E_ the steric s I k ) s ' o ' a substituent parameter. Substitution of Eg into an

equation of the Hammett form produces the TAFT LINEAR

STERIC ENERGY EQUATION

i.e. log & - log k Q = £ .Eg ...... (B)

where S is a reaction parameter measuring the sensitivity of a reaction series to steric influences of substituents.

This equation correlates a limited number of reaction series

including

i) the hydrolysis of ortho substituted benzoates, and

ii) the hydrolysis of ortho substituted benzamides.

It is reasonable to assume that reaction series which are

affected by both the polar and steric influences of

substituents will be well correlated by a linear combination

of equations (a ) and (b ) and this process leads to the

equation

log k - logk0 = ^ ^ ^ ...... (c )

i.e. a TAFT FOUR-PARAMETER EQUATION.

# # If, as is assumed, (T~ and E are independent variables, S then equation (c) represents a planar free energy

relationship.

For each of the above equations, when applied to aliphatic 27 reaction series the parent series is the hydrolysis of ethyl acetate and substitution in the series is in terms of substitution of the methyl group.

14 Reaction series have been studied which appear to be influenced only by the polar effect of the substituent, but are also perturbed by an effect proportional to the number of alpha*-hydrogens in the substituent. Taft equations of the type

log k - log kQ = p * h(n -3^ ...... (d ) have been used to quantitatively assess this presumably hyperconjugative effect. Similar equations have been used to assess hyperconjugative perturbations in reaction series which are affected by both the polar and steric influences of substituents 34 . These are six parameter equations of the type

log k - log kQ = f* + £ ’ + h(fi-3^ ...... (E) but to date these have not been extensively used.

In equations (D) and (E) above

h = a reaction parameter measuring the effect of hyperconjugation

n = the number of alpha-hydrogens in the substituent and the remaining symbols are as previously defined. The existence of Taft equations and of tables of the and Eg values for common substituents, allows the quantitative separation of the polar and steric influences of a substituent.

Best results are obtained where a wide variety of group types are studied since large variations in the magnitude of the

CT"if and Eg parameters make separation of the effects easier.

An examination of Taft*s derivations indicates that many assumptions have been made. On the whole these assumptions appear reasonable although some are hard to justify by

q K q / rigorous argument. ^ ^ The principal justification of the equations rests not so much on the validity of the assumptions, but on the fact that the results obtained fit in so well with other knowledge of steric and electronic effects.

In defining steric parameters Taft reported a parallel between the E substituent cons taints and the Van der WaaJg*^ s O Q radii of the substituents. ChartonJ has made a theoretical correlation of steric parameters with Van der ¥aaJs!^F radii and has shown that the E values for the substituent types

-CH X, -CHX and -CX are a linear function of their X* ^ ^ Van der Waals1^ radii, i.e. the Eg substituent parameters represent the effective size of the substituent. Since the E values are independent of electrical and other s effects they should be additive. Charton postulates the non-additivity of steric effects as being due to conform- ational effects in the substituents. 29 Taft defined polar substituent constants in terms of

the acidic and basic hydrolysis of esters by the

expression

^ * = 2 4 8 [ k>g(£j# - 'og(j^ J ...... (3 )

since it was believed that steric effects were comparable

in both media. Recent work upon the role of the solvent

in hydrolysis^ ’ has cast doubts upon the completeness

of elimination of the steric effect in equation (3).

39,40 ^ Charton ’ has re-defined Oj constants, and hence o

in terms of the pK^ of substituted acetic acids in water.

Steric effects are generally negligible and since this

technique requires only one measurement it is more

convenient than the Taft procedure described above.

D. HYDROLYSIS OF AMIDES

Reid 4i ’ 42 has shown that the hydrolysis of amides is .

catalysed by both acids and bases and that the reaction

is first order with respect to both the amide and the

catalyst, i.e. second order overall.

Mechanism of the Acid Catalysed Hydrolysis

The generally accepted mechanism for the hydrolysis of S amides in dilute acidic solution is that due to Bender 30 43 and involves an A. JZ substitution, i.e. a protonation of the amide (a ) to form its conjugate acid (b ), followed by a slow rate determining addition of water, to form an sp3 transition state, which undergoes rapid decompos­ ition to form the hydrolysis products.

This mechanism gains strong support from two sources of experimental evidences- a) the effect of increasing acidity upon the reaction

rate, and b) the influence of polar substituents upon the reaction

rate.

The effect of variations in pH upon the reaction rate is summarised in Figure 2. FIGURE 2. 31

solutions any increase in the concentration of acid catalyst will result in a proportional increase in the

concentration of the conjugate acid (b )* Thus the reaction assumes a second order kinetic form, viz,

“ dt = k[AmideJ[ h/]

and increases in velocity with increasing acidity until

the amide is completely protonated. The section of

Figure 2 from W-X has been shown experimentally

to correspond to this postulated second order form*

The decrease in the reaction rate, corresponding to the .k69k7 portion of Figure 2 between X and Y, is considered ' 32 to be due to a decrease in the concentration or activity of free water molecules in the reaction mixture due to increasing solvation forces^’ Since the formulation of the transition state (c) requires an addition of a water molecule to the conjugate acid (b ) any significant decrease in the concentration of "free” water will retard the 49 hydrolysis. Edward and Meacock have since verified these assumptions and quantitatively assessed the effect of increased acid strength upon the reaction rate.

The portion of Figure 2 from Y to Z, corresponding to an increase in the hydrolysis rate, was investigated by

Duffy and Leisten 50 . The increase in the hydrolysis rate was found to be the result of a mechanism change in which hydrolysis proceeds by an A^^l mechanism, i.e. a unimolecular mechanism involving heterolytic fission of the amide into an acylium ion. The assumed mechanism is

RCONH® ------J- R.C 0® + NH 3 3

R-C-0® -b H,0 ------► RC00H®

NH + H® ------* NH® 3 ^

This mechanism would, as experimentally predicted, be facilitated by increasing acid concentrations.

The second piece of evidence supporting the A-^2 mechanism for acidic amide hydrolysis concerns the effect of polar substituents upon the reaction rate in the range W-X of 33 Figure 2. The two steps of the mechanism, i.e. the protonation (l) and the of a water molecule (2), are affected by the polar influences of substituents in opposite directions, e.g. electron withdrawing substituents (methoxy , halogens, etc.) favour the protonation, but hinder the addition of water. In dilute acid, where both mechanistic steps are significant, the presence of substituents with large polar substituent constants has been shown 51 to have little effect upon the hydrolysis rate. However, in more concentrated acid solutions, (region X-Y), where the protonation of the amide is complete, the effect of polar substituents on the reaction rate is as expected for the nucleophilic addition of water to a carbonyl carbon atom, i.e. electron withdrawing groups favour the hydrolysis.

Mechanism of the Base Catalysed Hydrolysis 52 Prior to 19^5 it was generally accepted that the base catalysed hydrolysis of amides (which corresponds to the region V—W in Figure 2), occurred by one of the two following mechanisms

Mechanism 1 ^ ^ kn 9 RCONH +0H ^ — R -Ç -N H 2 * RCOO i- 2 -a OH (A ) (B) i.e. a two-step B I substitution. AO Mechanism 2 34 ,<=> s> 9 « RCONH +0H HO--C-NH •*- HO-C +NH - >RCOO+NH. • 2 R k 2

i.e. a one-step concerted SN^ displacement mechanism.

Bender 53 , in his mechanistic investigation of the analogous

basic hydrolysis of esters, differentiated between the two

mechanisms by the use of 0 18 tracer experiments in which he

labelled the carbonyl oxygen with 0 18 .

The carbonyl addition mechanism (Mechanism l) predicts

the formation of a transition state (b ) in which the two oxygen

atoms are equivalent. If k is significant with respect —a to then the expulsion of the attacking OH nucleophils

would involve the loss of either the labelled or non­

labelled oxygen at comparable rates, i.e. a decrease in

the 0 18 content of the unreacted could be expected.

Bender noted this decrease in the hydrolysis of three

different esters and concluded that the carbonyl addition

mechanism must be in operation since the SN^ type mechanism 18 offers no satisfactory explanation for the loss of 0 .

Bender and Ginger^ found that the basic hydrolysis of

benzamide also exhibited carbonyl oxygen exchange and

concluded that the basic hydrolysis of amides occurs by

Mechanism 1. 35 5 5 56 Swain and Breslow however, have independently

suggested that this evidence is not conclusive since, if k > k , exchange could occur by the first step of

Mechanism 1 while hydrolysis occurs by Mechanism 2 as

concurrent independent reactions.

Schowen, Jayaraman and Kershner 57 ' , in their study of the hydrolysis of 2.2.2-trifluoro-N-methylacetanilide in

concentrated base solutions, have demonstrated a change

in the rate determining step of the mechanism, i.e. in

solutions of low basicity the decomposition of the

transition state (b ) to the products is rate determining, while in highly basic solutions nucleophilic addition of

0H~ to the amide (A) is rate determining. The presence

of a change in rate determining step indicates that a

two-step mechanism, presumably Mechanism 1, controls the basic hydrolysis of amides.

Early Structure-Reactivity Correlations for Amide Hydrolysis

The first attempt at a quantitative structure-reactivity

correlation of the hydrolysis of aliphatic amides was 2 . . made by Bruylants and Kezdy using the results obtained from the acidic hydrolysis of thirteen compounds. It was claimed that by measuring the rate constants in dilute

sulphuric acid solution at various temperatures, the difficulties involved in working in concentrated media were eliminated and only the effects of structural variations were in evidence. 36

Examination of the reaction rates at a specific temperature led to the immediate recognition of a qualitative correlation between the hydrolysis rates and substitution in that "amides showing the same degree of substitution undergo hydrolysis with rates of the same order of m 2 magnitude . The degree of substitution, (n ^) was 58 calculated using Newman's Rule of Six where is the mean value of the number of atoms held in the sixth position with respect to the oxygen and hydrogen atoms of the amide group.

This qualitative correlation suggested the existence of a quantitative correlation between the acidic hydrolysis rates and the steric influences of the substituents. To confirm this Bruylants used the Taft equation

in which the parameters have the previously discussed meanings. By assuming that JD = O as is the case in the analogous acid hydrolysis of esters, Bruylants found that the data was well correlated by a Taft Linear Steric Energy

Equation of the type

1'06 S.

From this Bruylants deduced that Mthe acid catalysed hydrolysis of amides is not dependent on polar effects 37 and that the rate is governed by the steric influence of 2 the substituents only".

Using the alkaline hydrolysis rates for the same thirteen amides plus the three chloroacetamides 59 Bruylants used a

Taft equation of the type

linear plots with good correlation co-efficients. From this he concluded that the alkaline hydrolysis was governed by both the polar and steric influences of the sub s ti tuent s.

One of the conclusions drawn by Bruylants and Kezdy, namely that the acidic hydrolysis of amides is independent of polar substituent effects, can be criticised on the grounds that all of the substituents considered had small or negligible polar substituent parameters. Furthermore almost all of the experimental results produced by

Bruylants and his co-workers have been thrown open to 3 question by Bolton and Wilson1s report that Bruylants failed to allow for the incompleteness of the second stage of ionisation of the sulphuric acid catalyst. Bolton and 4 . . Wilson derived a correction procedure which involved multiplication by a constant factors

measured rate constant for acetamide i . e. in HC1 at 75°C 10.3 = 2.19 measured rate constant for acetamide 4.7 in H S0^ at 75°C 38 Application of the correction procedure led to results which, were still ten to fifteen percent below the results obtained for hydrolyses carried out in completely ionised acids. Bruylants however, had carried out all the rate determining reactions in consistent conditions so it was possible, to a first approximation, that his ^ log k

(= log k - log kQ) values were accurate despite the errors in his absolute rate constants. 39

EXPERIMENTAL A. PREPARATION AND PURIFICATION OF AMIDES

The amides used in this investigation were either available as commercial samples or were prepared by one of the following methods:

Method 1.

The acid chloride was prepared from the parent acid

and added slowly to dry benzene through which was

passed an excess of anhydrous ammonia.^

Method 2 .

The ethyl ester was prepared from the parent acid^2

and was then added slowly to aqueous ammonia at room

tem perature.^

The amides were purified by repeated crystalisation from chloroform/petroleum ether mixtures to constant melting point

Table 1 summarises the data used as a criterion of purity and indicates which method of preparation was used for each amide.

Other solutions used were prepared from reagents of analytical reagent quality and standardised by normal methods

Deionised water was used for all solutions and as the solvent in all kinetic determinations. 41 TABLE 1

Accepteda * .64 Melting Method Melting Point of AMIDE Point C Found Preparation*

ACETAMIDE 82-3 8 0 . 5 C

PROPANAMIDE 81-3 81.2 C

BUTANAMIDE 115-6 1 1 6 . 6 C

VALERAMIDE 1 0 6 . 0 1 0 5 * 0 C

ISO-VALERAMIDE 137*0 1 3 6 - 7 A

METHOXYACETAMIDE 9 6 . 5 97.0 C

3.3-DIMETHYLBUTANAMIDE 1 3 2 . 0 1 3 2 . 5 - 3 3 C

C YCLOHEXYLACETAMIDE 1 7 1 - 2 171.5 A

PHENYLACETAMIDE 1 3 7 . 0 1 3 6 . 6 C

CHLOROACETAMIDE 119.5 118.5 B

H • 0 90.8 B BROMOACETAMIDE VO

2 -ETHYLBUTYRAMIDE 1 1 2 . 0 1 1 1 - 2 A

2 -METHYLBUTYRAMIDE 111.0 1 1 1 . 2 A

CYCLOHEXANECARBOXAMIDE 1 8 5 • 6 185.4 A

C YCLOPENTANECARBOXAMIDE 179*0 180.0 A

ISO-BUTYRAMIDE 1 2 8 . 0 128.4 C

TRIMETHYLACETAMIDE 1 5 2 - 3 1 5 2 . 6 C

TRIETHYLACETAMIDE 108.0 107.4 A

2.2.-DIMETHYLBUTYRAMIDE 104.0 100* C

* Sublimes A Method 1 B Method 2 C Commercial Sample 42

B. KINETIC METHODS

i) Survey of Techniques used by Previous Workers

The overall reaction for the acidic and basic hydrolysis of amides can be represented as

© RCOOH + NH^

r c o n h 2 + h 2o O OH e> RCOO + NH Base 3

In order to follow the kinetics of the reaction, it is necessary to determine the change in concentration of one or more of the species present, but to date no single method has been found to be sufficiently general to be of universal use. The failure of a universal method to evolve in the past can be attributed in part to the following factors

a. the large variations in rate constants produced

by simple substitutions.

b. interference of substituents in the amide with

reagents used in the analysis.

c. the low solubility of some of the di- and tri-

substituted amides, and 43 d . complications due to side reactions involving

the hydrolysis products of certain amides.

Previously available studies of amide hydrolysis have led to the development of five major techniques for kinetic studies of the reaction:-

1) Direct analytical determination of the ammonia formed during the reaction.

2) Indirect determination of the ammonia formed using

Nessler colorimetric methods.

3) Potentiometrie titration; usually of the carboxylic acid product.

4) Ion-Exchange separation followed by the use of 1, 2 or 3 •

3) Spectrophotometrie determination of unreacted amide in the U.Y. region.

In most reported kinetic studies of the reaction, known amounts of amide and catalyst are mixed in pyrex tubes, sealed and placed in a thermostat. After measured periods of time the tubes are removed, the reaction quenched by cooling in ice water and the appropriate analysis conducted.

1: Direct Analytical Techniques

Rabinovitch and Winkler 6 J5 in their investigation • . of the acid hydrolysis of formamide, acetamide, propionamide and 44 benzamide used Folin's Aspiration Method of Analysis^ of the ammonia formed to follow the reaction.

f t Bose, 7 in a comprehensive study of the acid catalysed hydrolysis of acetamide in both water and aqueous organic solvents, followed the reaction by estimating the ammonium salts produced, using a slight modification of the Kolthoff formaldehyde method wherein the reaction mixture was first neutralised with sodium , the solution (containing the ammonium salts) treated with excess formaldehyde, and the acid liberated titrated with standard base.

For the hydrolysis of the chloroacetamides, Bruylants and his co-workers 59 titrated ammonia oxidimetrically by means of potassium hypobromite, detecting the end-point by potentiometrie dead-stop measurement. Packer, Thompson and Vaughan 68 also used this oxidimetric method to study the basic hydrolysis of four aliphatic amides and five para alkylbenzamides.

2: Nessler Colorimetrie Techniques

Bruylants and co-workers2,^ ’^° have used the Nessler

Colorimetric method of ammonia determination extensively to investigate both acidic and basic amide hydrolysis. The reagent, an alkaline solution of mercuric iodide in potassium iodide, when added to the dilute ammonium salt solution, forms an orange-brown complex which can be visually compared 45 with, known standards or determined colorimetrically

using a spectrophotometer.

3 • Potentiometrie Titration Techniques

Soundararajan. and Void 71 used potentiometrie titrations of

both the remaining catalyst acid and the organic acid

formed during the hydrolysis in their studies of the acid

hydrolysis of chloroacetamide.

Mazzucato, Foffani and Cauzzo 72 , in their study of

environmental and substituent effects on the rate of the

basic hydrolysis of N-methylacetamide and N-N-dimethylacetamide

and the acidic hydrolysis of N-methylacetamide, used a

similar technique to determine the amount of acetate formed.

4 Bolton and Wilson used a modification of the above

techniques in that the first derivative plots of the

titration curves were used to obtain the concentrations of

the remaining catalyst acid and the organic acid produced.

4 î Ion-Exchange Techniques 2 7 3 74 . Bruylants and co-workers ’ ’ followed the reaction by

passing the reaction mixture through a column of a strongly

acidic cation-exchange resin.

As a typical reaction mixture contains the following species: <& & © r c o n h 2 h 3o Cl RCOOH NH. ^ ------.------V Unused Catalyst Spectator Products Amide Acid Anion 46 such, a passage would leave all species unchanged except the ammonium ion which would be quantitatively exchanged for hydroxonium ion. The ammonium ion concentration is then found by determination of the increase in the hydroxonium ion concentration.

2 74 Bruylants ’ also used an anion exchanger, followed by a potentiometric titration determination of the organic acid, obtaining very accurate results for the complex hydrolysis of succinamide.

Bolton and Henshall 75 studied the cation-exchange resin catalysed hydrolysis of seven amides including three

N-substituted amides wherein the acid catalyst and amine were filtered off and the organic acid determined by titration. Potentiometric titration of the resin allowed for cross-checking of the results.

5: Spec trophotometric Techniques

2 7 6 • Bruylants and co—workers 9 have reported that the amide group shows a typical and selective band in the U.Y. region within 200-300m/J , such that the change in concentration of amide with time can be followed by measuring the optical density of the reaction mixture.

However, more recent work^ ’ ^ has shown that no such absorption bands exist for aliphatic amides in this region.

The bands which Bruylants claims to have used occur in 4 / fact at about 185-1901X1,11 , well below the range of the equipment Bruylants used. His results obtained for the alkaline hydrolysis of acetamide are therefore questionable.

Aromatic amides exhibit suitable absorption bands in the 250-3000^1 region and Edward and Meacock^ have used a spectrophotometric technique to study the acidic hydrolysis of benzamide, para-methoxybenzamide and para-nitrobenzamide. go Katritzky and Waring studied a similar series of amides by this technique as part of their examination of the non-applicability of amides to the Hammett Acidity Function.

C. TECHNIQUES USED IN THE PRESENT WORK

A close examination of the methods used by previous workers indicated that the potentiometric procedure had the most general application and was capable of a high degree of precision. With this in mind, this technique was selected as the basic kinetic procedure for the present work.

1. Potentiometric Technique - Experimental Method

The hydrolysis was carried out in a series of Pyrex glass reaction vessels of capacity 22 ml. The tubes were cleaned by standing in R.B.S.-25 detergent at room temperature for at least twelve hours before being washed in distilled water. FIGURE 1

Automatic Titration Apparatus

QO After drying overnight the tubes were ready for use. By means of a 10 ml pipette an aliquot of amide solution was added to each tube. A similar aliquot of pre-heated catalyst was added to each tube, the tubes sealed with pyrex stoppers and placed in a thermostated bath. The thermostats used in the present work were capable of maintaining the temperature to better than 1 0.05 centigrade.

After a measured period of time a tube was removed, quenched in ice water and analysis commenced immediately.

Analysis of the sample was achieved by transferring a 5 ml aliquot of the reaction mixture to the titration vessel of a Radiometer” automatic titration unit. (Fig. l) .

This equipment records the titration curve of any potentio- metric titration i.e. a curve showing the electrode potential as a function of the volume of titrant added. The titrant,

0.2 normal , was added to the titration vessel through a plunger driven syringe burette automatically

0.001 ml at a time. A vacuum glass electrode, of type

Radiometer G2021C, was used in conjunction with a saturated calomel electrode, of type Radiometer K402, to measure the changing potential of the solution thus producing a titration curve as shown in Fig. 2. From the titration curve the concentrations of both the remaining catalyst acid and the parent organic acid formed can be determined. These, when used in conjunction with standard rate equations, produce FIGURE 2

Potentiometrie Titration Curve ©•/ •h t •h

O LO 51 results of* high, precision and reproducibility.

2. Ion-Exchange Technique

Two factors limiting the use of the titration technique have been:- a. the relative strength of the parent carboxylic acid i.e. the carboxylic acid produced during the hydrolysis must be a sufficiently weak acid to allow an inflection point to be obtained between it and the catalyst acid. If

the carboxylic acid is too strong, then no inflection is

formed, and the concentration of the remaining catalyst

acid cannot be determined.

b. the higher amides e.g. phenylacetamide and cyclohexylacet-

amide are insufficiently soluble in water to allow optimum working concentrations to be attained.

The first of these difficulties was encountered in the hydrolysis of the haloamides, but was overcome by the use

of an ion-exchange technique.

Ion-Exchange Technique - Experimental Method. The

experimental method, used previously for the titration

technique, was followed up to the point where the samples were removed from the thermostat. The reaction was then quenched by pouring the reaction mixture into ice-cold deionised water (25 ml.). The reaction tube was washed

out with deionised water and the washings added to the diluted reaction mixture. This solution was then passed through a column containing the sulphonic acid cation exchanger Amberlite I.R.120 and the column washed with deionised water until the total volume of the reaction mixture and the washings was 250 ml. To ensure that all the reaction mixture had been washed through the column, a test was made for chloride ion in the washings using a concentrated AgNO^/HNO^ solution. In all cases it was found that the washings were Mclean11 by the time the total volume was 250 ml.

The reaction mixture was then analysed by transferring an aliquot, by means of a 50 ml pipette, to the titration vessel of the previously described Radiometer Automatic

Titrator and titrating to pH 7*0 with standard sodium hydroxide.

Ten millilitres of the catalyst acid were diluted to

250 ml and titrated in the same way as the reaction mixture;

the difference between the titrations being proportional to

the ammonium ion concentration.

The efficiency of the analytical technique was tested by hydrolysing acetamide under acidic conditions and comparing

the results with accepted values . The results of the

comparison are summarised in Table 2. The precision and reproducibility of the method was found to be adequate for the successful evaluation of the reaction parameters 53 of the amides although, not as good as that achieved by

the previously described titration technique.

Preparation and Maintenance of Columns. The Amberlite

I.R.120 resin was pretreated by standing in dilute hydrochloric acid for twelve hours followed by extensive

washing with deionised water. The theoretical amount of

resin required for complete exchange was calculated and

then four times this amount was placed in the columns. The

columns were regenerated after every use by passing dilute

acid (lOO ml of 0.2N HCl) through the column and then

washing with deionised water until no free chloride ion

was detected.

3. Conductimetrie Titration Technique

Because of the speed of the hydrolysis of the haloamides

and of the possibility of catalysis by the exchange resin,

it was thought necessary to check the results using an

independent method. Classical methods for determining

the ammonium ion concentration were avoided, for reasons

previously stated, and a conductimetrie method was employed.

This method is based on the principle of observing the

changes in conductivity of a solution in which a highly

conducting species is converted into a less conducting . . .. species during the course of an acid-base titration4 81 . At

any stage during the hydrolysis FIGURE 3

Thermostated Conductivity Cell 55 RCONH >. RCOOH NH + N H 4, L____ V— ------Highly Less Conducting Conducting the sum of the acid concentrations is constant. If enough standard alkali is added to neutralise this amount of acid then any further addition of alkali will be used in titrating the conducting ammonium ion into the non-conducting ammonia molecule.

Conductimetrie Titration - Experimental Technique. The experimental technique prior to removal of the tubes from the thermostat corresponded to that previously described for the potentiometrie method. The reaction mixture was quenched in 20 ml of ice water, washed into a thermostated ■f* o cell, capable of maintaining the temperature to - 0.05 C, and diluted to approximately 50 ml with deionised water.

Using the Radiometer titration apparatus previously described a calculated amount of standard base was added to neutralise the solution. Two platinised electrodes, approximately

0.5 cm. square, were inserted into the solution (Fig. 3) and attached to a Yangimoto Conductivity Outfit Model MY-7.

(Fig. 4). Aliquots of base, approximately 0.01 ml per addition, were then made using the titration apparatus and, after leaving the cell to equilibrate for two minutes, the conductance was measured. The concentrations of the reactants were adjusted so that during the titration the FIGURE k

Yangimoto Conductivity Apparatus

-C0N01NSlR- KOI 10 01 XO 001 XOOOOI MAGtC-CTC SCNS to . JO 45 3 45 SOURCI

:D LO increase in the volume of the solution was negligible. A series of at least eight volume/conductance readings were made before and after the end-point. Visual inspection of a graph of volume against conductance was used to omit any obviously deviant points. An I.B.M. 1620 c o m p u t e r system was then used to draw the least squares line of best fit through the points before and after the end-point and to calculate their point of intersection i.e. the end point of the titration.

Treatment of the results with standard rate equations yielded rate constants in excellent agreement with those obtained from the ion-exchange technique i.e. to within

- 0.9# (c.f. Table 2).

T A B L E 2

R a t e s of the Acid-Catalysed Hydrolyses of Acetamide at 75°C

$ Deviation from x ^ METHOD 10 Accepted Value

TITRATION 4 1.03 -

ION-EXCHANGE 1.02 i 0.5

C ONDUCTIMETRIC 1 . 0 5 i 0.9

CONDUCTANCE 1.02 0.5 j •“. - ' w

FIGURE 5

High Precision Resistance Cell 4. Conductance Method 53

The methods described so far were applicable to the study of the hydrolysis of most amides; the exception being amides with low water solubilities. The need to develop a

technique to handle the hydrolysis of relatively insoluble amides and the need for a method capable of following high

speed hydrolyses, suggested that a physical method be

investigated. Variations in the conductance of reaction mixtures had been extensively employed in the related field 82 of ester hydrolysis for both acid and basic hydrolyses, but O O had rarely been reported, except by Crocker J early this

century, as a method for the study of amide hydrolysis.

The technique depends upon the fact that the conductance

of a solution is directly proportional to the concentration

of the reactant under consideration. In this case the

change in resistance of the reaction mixture was measured

as the highly conducting catalyst acid was replaced by the

less efficiently conducting hydrolysis products.

Resistance Technique - Experimental Method. A high

precision resistance cell was constructed as shown in

Fig. 5. To a known weight of amide, weighed directly

into the cell, was added sufficient standard catalyst to make the concentrations of the reactants equal. The cell,

in conjunction with the conductivity outfit previously

described, was then used to obtain a series of time/ resistance pairs which, when treated with standard rate GO equations, gave usable rate constants

Difficulty was encountered, however^ in obtaining accurate values of R (resistance at Zero time) and R A

(resistance at infinite time) due to tbe slow hydrolysis rates of some of tbe amides. Tbe manner in which these difficulties manifested themselves was that the standard second order

(equal initial concentrations) rate equation

]_ 1 ktA / 1 R R t o °v R ) gave results which were not always satisfactorily reproducible. This was overcome in two ways:-

1) by measuring the resistance of solutions made up to correspond to the composition of the reaction mixture at zero and infinite time.

Solution: Since the amide has negligible conductance

R q is found by measuring the resistance of a solution of

equal volumes of the catalyst and deionised water at

the temperature of the hydrolysis.

R Solution: Found by measuring the resistance of a

solution containing the hydrolysis products at the

desired concentrations at the temperature of the

hydrolysis•

2) It was found that a computer orientated method offered a more rapid, and just as precise method, of obtaining table: 3

ACETAMIDE AT 75 DEGREES EXPERIMENTAL SUBROUTINE TIME RESISTANCE RATE CONSTANTS RATE CONSTANTS 8 5 . 2 5 9 3 . 7 9 1 . 2 3 3 7 E-C3 1 .C2 2 2 E-C3 1 1 5 .CC 1 0 C.4 C 1 . 1 9 1 4 E -03 1 .C1 8 9 E-C3 1 4 1 .CC 1 0 6 . 1 C 1 . 1 8 C5 E-C3 1 .C2 6 7 E-C3 1 7 2 . 5 C 1 1 2 . 1C 1 . 1 5 9 3 E-C3 1 .C2 C1E-C3 2 C5 .5 C 1 1 8 .3 C 1 . 1 5 9 3 E-C3 1 .C2 7 7 E-C3 235.cc 1 2 3 . 2 C 1 . 1 5 7 1 E-C3 1 .C2 9 CE-C3 0 £ n no 127.cc 1 . 1 5 6 8 E-C3 1 .C2 9 8 E-C3 2 9 3 .5 C 131.5c 1 . 1 5 5 IE-03 1 . 0 2 7 5 E-C3 3 2 C.75 135.2c 1 . 1 6 8 8 E-C3 1 .C3 7 1 E-C3 3 4 9 .5 C 137.9c 1 . 1 5 7 1 E-C3 1 .C2 3 5 E-C3 RESULTS USING EXPERIMENTAL DATA LEAST SQUARES RATE CONSTANT = 1 . 1 4 C3 E-C3 AVERAGE RATE CONSTANT = 1 . 1 7 1 9 E-C3 CORRELATI ON COEFFIC1 ENT = 9 . 9 9 8 2 E-C1 STANDARD DEVIATION FROMMEAN = 1 . 1 7 2 2 E-C3 PREDICTED INFINITE RES! STANCE = 1 5 8 . 4 0 PREDICTED ZERO RESI STANCE = 69.IC CATALYST CONCENTRAT! ON = .0 3 1 2 N AMIDE CONCENTRATI ON = . 11 03 N RESULTS USING VARIABLE INFINITY SUBROUTINE LEAST SQUARES RATE CONSTANT 1 .C3 2 1 E-C3 AVERAGE RATE CONSTANT 1. 0 2 63 E-C3 CORRELATION COEFFICIENT 9 . 9 9 9 CE-C1 STANDARD DEVIATION FROM MEAN 2 .3 5 5 2 E-C5 PREDICTED INFINITE RESISTANCE 1 62,67 PREDICTED ZERO RESISTANCE 7 2 . 4 8 PERCENTAGE OF REACTION FOLLOWED 8 5 . 5 5 CD accurate values of R and R_. o An I.B.M. 1620 digital computer was used to adjust the values of R ^ by an iterative procedure until plots of l/R - l/R^ against l/R^ showed maximum linearity. The use of this procedure can be justified where the second order nature of the reaction is well established, as in the present case, and the curvature of the observed kinetic plots can be attributed to a particular experimental difficulty. The adjustment required was always small (of the order of 2-3 ohms in an R ^ value of

150-200 ohms), but resulted in a considerable improvement in the reproducibility of the rate constants obtained.

Table 3 shows the results for the hydrolysis of acetamide in dilute acid at 75°C in which the rate constants w£re calculated using both the experimental values of R q and

and the ’’variable infinity” subroutine described above.

The improvement in linearity of the kinetic plot produced by the subroutine is evidenced byj-

a) the improved linear correlation co-efficient, and

b) the improved standard deviation from the least

mean squares rate constant.

In the case of 3 .3-dimethylbutyramide two independent methods were used for the hydrolysis at 75 C. The results, as summarised belowJ

METHOD TITRATION CONDUCTIVITY -4 -4 Rate Constant 1.123 x 10 l.ll6 x 10 63 T A B L E 4

METHOD USED AMIDE

ACID HYDROLYSIS BASIC HYDROLYSIS

ACETAMIDE T, E , R a n d C T a n d R

PROPANAMIDE R R

BUTANAMIDE R R

VALERAMIDE T a n d R R

I S O - V A L E R A M I D E T R

METHOXYACETAMIDE T R

3.3-DIMETHYLBUTANAMIDE T a n d R -

CYCLOHEXYLACETAMIDE R R

PHENYLACETAMIDE R R

CHLOROACETAMIDE E a n d C -

BROMOACETAMIDE E -

2 -ETHYLBUTYRAMIDE T a n d R - 2 -METHYLBUTYRAMIDE T R

CYCLOHEXANECARBOXAMIDE R R

CYCLOPENTANECARBOXAMIDE R R

ISO-BUTYRAMIDE R R

TRIMETHYLACETAMIDE T R

2.2 ,-DIMETHYLBUTYRAMIDE R

T: T i t r a t i o n Ei Ion ExcHange

R: R e s i s t a n c e C: Conduc timetrie indicate the excellent agreement between the two techniques i.e. to within i 0.3$•

The resistance method, coupled with the computer programme described above, appears to be the most universal method for the hydrolysis of amides and has the added advantage that continuous measurements can be made on a single sample. The method has been used extensively in the present work for the basic hydrolysis of amides with an occasional check run being done using the titration technique.

The resistance technique cannot be used for the acidic hydrolysis of the haloamides since the low concentration of catalyst acid required to obtain optimum resistance changes makes the "secondary catalysis" produced by ionisation of the parent haloacid a significant factor. However, these amides can be easily handled by use of the ion-exchange or potentiometric titration technique where an excess of catalyst acid can be used to suppress the ionisation of the parent acid. Table 4 summarises the various techniques used for the hydrolysis of each amide.

Volume Correction Factors. Since solutions were standardised at room temperature (20 C) , but were used at temperatures ranging from 45-95°C, it was necessary to adjust the rate constants obtained to compensate for the thermal expansion of the solvent. The correction was 65 obtained by multiplying tbe rate constant obtained by a volume correction factor, VFAC, where

VFAC — ■reaction■ ■ ■ ... - ■ volume■ . .. —... at. bath temperature reaction volume at room temperature

For water and dilute aqueous solutions tbe values of

VFAC used are summarised below:-

TEMPERATURE °C VFAC

45 1 . 0 0 6 55 1.012 65 1.018 75 1.024 85 1.030 95 1 . 0 3 6 6 6

DISCUSSION A* DISCUSSION OF THE RESULTS OP THE ACID HYDROLYSIS OF AMIDES

Under the conditions pertaining the kinetics of the

hydrolysis were found to satisfy the rate equation

- d tV ’J - k2[H30*J[^lc>.]

i.e. the reaction was first order with respect to both

acid and amide and was thus second order overall.

Soundararajan and Void 71 reported a deviation from second

order behaviour in the latter stages of the hydrolysis of

chloroacetamide• Since this effect was not observed for

any amide in the present study it is apparent that it arose

from misuse of sulphuric acid catalysts by these workers.

Bolton^34 , in a re-examination and extension • of the

work of Bruy 1 ants and Kezdy 2 , made a quantitative structure-

reactivity correlation for ten aliphatic amides. The data

for the correlation were made up of the results obtained by

Bolton for the hydrolysis of acetamide, propanamide,

butyramide and iso—butyramide in completely ionised acids,

together with those of Bruylants after correction by the k Bolton-Wilson procedure.

It was found that the Taft linear steric energy

relationship log k - log k o = ^C .E s o • o (1 ) gave a reasonable correlation for the data and that no significant improvement in correlation could be obtained by fitting the Taft four-parameter equation -¥r , * log k - log k Q = p *Es ...... (2) to the data. Since the correlation included the polar

CICH^- substituent Bolton concluded that the acidic hydrolysis of amides was, as previously postulated, 2,10 insensitive to the polar influence of substituents.

In view of this, and similar conclusions drawn by 2 . . Bruylants and Kezdy , the results for the acid hydrolysis of the seventeen amides studied in the present work were tested using the Taft linear steric energy equation as above. A complete summary of the source data required for the Taft correlations at 75°C in both acidic and basic media appears in Table 1 • The results of the analysis and of those obtained by Bolton, are summarised in Table 2.

Bolton omitted the tert. butyl substituent from his correlation since the inclusion of this highly deviant group lowered the correlation co-efficient to a value of . ^ .2 7 0.919 which was considered "unacceptable” by the criteria commonly applied, at that time, to linear free energy relationships. In the present study a correlation co­ efficient of 0.93^ was obtained for all the amides studied T A B L E 1 6 9

SOURCE DATA FOR TAFT EQUATION ANALYSIS AT 75°C

a) Structural Formula * Trivial Nomenclature E E° n — lo g k — lo g k b) < r c) I.U.P.A.C. Nomenclature a c i d b a s e a) CH 3 -CONH 2 0.00 0.00 0.00 3 2 . 9 8 7 2 . 8 5 3 b) A c e t a m i d e

c) Et hanamide 1 o o t a) c h 3 c h 2 c o n h 2 -1 - 0.38 - 0.1 2 - 2.921 2 . 8 7 7 b) Propi onamide c) Propanamide a) c h 3 (c h 2 )2 c o n h 2 - 0.36 - 0.67 - 0.115 2 - 3 . 2 2 3 3 . 1 5 8 b) B u t y r a m i d e c) B u t a n a m i d e a) c h 3 (c h 2 )3 c o n h 2 - 0 . 3 9 - 0.70 - 0.130 2 - 3 . 2 2 7 3 - 2 4 9 b) V a l e r a m i d e

c) Pentanamide

CH 1 0

e - 3 . 8 8 8 a) ^ CH(CH2)2 CONH2 \D C3 - 1 . 2 4 - 0.125 2 3 . 7 0 8

C H 3 b) iso—Valeramide c) 4-Methylpentanamide in O 0 1 1 O H • a) CH3OCH2CONH2 VO 0 .5 0 2 3 . 0 4 7 1 . 9 1 1 b) Methoxyacetamide c ) 2—Me tHoxyetHanamide TABLE 1 (Contd.) 7 J a) Structural Formula * Trivial Nomenclature E E° n — log k — log k s s (T c) X.U.P.A.C. Nomenclature a c i d bas e

CH CH J J 3 \ ' a) C - CH —CONH - 1 . 74 -2. 0 5 - 0.165 2 4 . 7 1 5 - c h 3 b) tert Butylpropionamide c ) 3«3 Dimethylbutanamide N 1 0 0 0 a) ^ Ch)- ch2- c o n h 2 - 0.98 - 1 . 2 9 0 2 3 . 9 0 5 3.736 b) Cyclohexylacetamide c) 2-Cyclohexylethanamide l 00 o a) ^ O - C H 2-CONH 2 « - 0.69 O . 225 2 3 . 2 8 1 2.751 b) Phenylacetamide c) 2-Phenylethanamide -d- c\¡ O 1 a) c i c h 2 c o n h 2 • - 0.55 1.05 2 2 . 9 1 8 - b) Chloroacetamide c) 2-Chloroethanamide 1 00 0 1 a) B r C H 2 C O N H 2 -0.27 • 1 . 0 0 2 2 . 9 5 4 - b) Bromoacetamide c) 2— Br omo e t H an ami de

CH„ -d1 C0 I 3 O 0 H 1 • 1 a) CH0 - C - CONH0 ■ - 2 . 4 6 O 3 . 6 4 7 3 . 595 J 1 CH^ b) Trimethylacetamide c) 2.2 Dimettiyl Propanamide TABLE 1 (Contd.) 71 a) Structural Formula C * b) Trivial Nomenclature E E n —log k —log k c) I.U.P.A.C. Nomenclature a c i d b a s e

C 2H 5 a) C 2H 5 - C H - C O N H 2 -2.59 - 0 .225 1 4 . 7 5 6 - b) Diethylacetamide c) 2-Ethylbutanamide CH^ a) C 2H^ - C H - C O N H 2 - 1 . 1 3 -1.74 -0.210 l 3.822 3.773 b) q L -Methylbutyramide c) 2—Methylbutanamide

- 3 a) CH^ - CH-C0NH2 -0.47 -1.08 -0.190 1 3.218 3.186 b) iso Butyramide c) 2—Methylpropanamide a) —- C0NH2 -0.79 -1.4o -0.15 1 3.402 3.395 b) Cyclohexanecarboxylamide c) Cyclohexanecarboxamide a) © V—- C0NH2 - 0.51 -1.12 -0.20 1 3.044 3.120 b) Cyclopentanecarboxylamide c) Cyclopentanecarboxamide

KEY TO TABLE: E == Taft steric substituent constant s EC = Corrected steric substituent constant s * < r = Tait polar substituent constant

n = Number oT o C -hydrogens in the substituent 1Z T A B L E 2

ACIDIC HYDROLYSIS OF AMIDES - TAFT EQUATION ANALYSIS AT 75°C

EQUATION ( 1 ) - LINEAR STERIC E Q U A T I O N (2) - POLAR-STERIC

B o l t o n Present Work B o l t o n Present Work

No. of Substrates 9 + 17 16 + 9 + 17 16 + S 0 . 8 2 7 0 . 9 1 1 1.015 0.828 0.898 0.996 f* - - - - 0 . 0 0 4 0.037 0.061 l o g k Q — 2 • 8 8 8 - 2 . 8 2 7 - 2 . 7 9 5 - 2 . 8 8 8 - 2 . 8 3 7 - 2 . 8 1 2

C o r r . C o — e ff . 0 . 9 8 4 0 . 9 3 4 0.9 7 4 0 . 9 8 4 0 . 9 3 4 0 . 9 7 5

S.D. 0 . 0 8 0 0 . 2 0 1 0.131 0 . 0 8 0 O . 201 O .129

Deg. of Freedom 7 15 14 6 l4 13 t —Tes t 1 4 . 6 3 IO. 12 16.09 1 4 . 6 3 1 0 . 1 2 16.09

o H . 1 $ Significance Level • 0 . 1 $ O. 1 $ 0 .1 $ 0 . 1 $ 0

+ Deviant tertiary butyl group omitted.

VARIANCE RATIO F-TEST

Indication of1 tlie Significance of the Improved Correlation due to omitting Tert Butyl Group

Equation F Significance Level

Linear Steric 2.50 5$

Polar—Steric 2.57 7 ..i

-Es / 4 and this rose to 0.974 on omission of the tert. butyl substituent. However, a Variance Ratio F-Test* indicated that the improvement in correlation co-efficient, caused by the omission of the deviant group, was significant only at the 5$> level.

• . . As previously predicted 34 no significant improvement in correlation could be effected by fitting, by standard least squares techniques, the equation

log k - log kQ = f

The correlations above indicate that the acidic hydrolysis of amides is correlated to a reasonable degree of precision by the Taft linear steric energy equation and thus that the acidic hydrolysis is governed predominantly by the steric influences of the substituent. The influence of the polar effects of the substituents upon the acid catalysed hydrolysis of amides must remain in question since neither the present study nor that of Bolton contained sufficient substituents with large polar substituent constants to confidently decide the issue. Only two amides included in the present study had polar substituent constants which are non-negligible i.e. BrCH^- with <3 - 1»00 and CICH^ with (T = 1.05. Inspection of Figure 1 shows that these amides deviate from the linear steric energy plot by an

* See Appendix 2, page f££ amount greater than that attributable to experimental error. However, a variance ratio F-test shows that the improvement in correlation obtained by using equation (2) is significant only at the 10% level. Since it is expected that the influence of polar substituents would be small, if not negligible, then only those substituents with large polar effects e.g. C l y > with (T** = 2.65, would be expected to be significantly deviant.

Taft , in defining steric substituent parameters in

terms of the acid hydrolysis of esters, recognised that

they would almost certainly contain significant resonance

energy contributions. For correlations involving E s parameters to be successful, these resonance contributions

must be either negligible or constant throughout the

reaction series. In the present reaction series, and

that considered by Bolton , the number of alpha-hydrogens

present in the amides varied due to substitution, so that

the "hyperconjugative resonance effect”, used here in the

sense of alpha-hydrogen bonding with the TT-electron system

of the reaction centre, must also be expected to vary.

By considering amides with two alpha-hydro gens only

i.e. by maintaining this hyperconjugative effect constant,

Bolton"^ obtained a significantly improved correlation and

concluded that hyperconjugative effects are not negligible

in the dilute acid hydrolysis of amides. In view of this the results for the hydrolysis of ten amides of the type

(X is any other group or atom other than hydrogen) were examined with the aid of equation (l). A similar analysis was made for five amides of the type -CHX^ and the results of these correlations are summarised in

Table 3 and illustrated in Figures 1 and 2 respectively.

TABLE 3

TAFT LINEAR STERIC ENERGY EQUATION ANALYSIS AT 75°c

■CH^X Substituents -CHX^ Sub s t i tuent s

No. of Substrates 10 5

l 1.131 1.094 log k o -2.780 -2.581 Corr. Co-eff. 0.992 0.993 S.D. 0.072 0.072

Degree of Freedom 8 3 t-Test 22.25 14.54 H O Significance Level • 0.1#

Studentfs t-tests indicate that the improved correlations obtained when the hyperconjugative perturbation is maintained constant for a series of amides are extremely significant i.e. hyperconjugative effects exert a significant influence upon the acid catalysed hydrolysis *

* See Appendix 2, page f $ 3 of amides. Insufficient data are available to allow a similar analysis to be made for the series of amides with no alpha-hydrogens i.e. no hyperconjugative effect.

Hancock, Tj^ers and Yager^ claim to have removed the hyperconjugative effect due to alpha—hydrogens from the

Taft steric substituent parameters by defining a "pure steric parameter", E°, such that s

E® = E g + 0,306(n-3)

where n is the number of alpha-hydrogens

and the factor 0*306 was obtained from M.O.

calculations•^

The Taft linear steric energy equation (equation l) was used to correlate the data for the hydrolysis of the seventeen amides of the present work against the pure steric substituent parameters defined above. The results of this correlation, and a similar correlation in which the deviant tert. butyl group was omitted, are summarised in Table k.

Studentfs t-tests show that the correlation co-efficients are extremely significant i.e. that the steric influences of a substituent play a dominant role in controlling the reactivity of amides undergoing acidic hydrolysis.

However, since the values of the correlation co-efficients are not close to unity it is apparent that the "steric- / S Ì TABLE 4

CORRELATIONS USING THE "PURE" STERIC ENERGY PARAMETERS AT 75°C

LINEAR STERIC ENERGY EQUATION (l)

No. of Substrates 17 16+

S o . 656 0.802 log k -2.734 -2.627

Corr. Co-eff. 0.833 0.903

S.D. 0.313 0.249

Degree of Freedom 15 14 i-Test 5.83 7.86

Significance Level 0.1$ 0.1$

+ Tertiary butyl group omitted.

VARIANCE RATIO F-TEST

Significance of Improved Correlation due to Omission of tert. butyl Group. Significance F Leve1

Equation 1 1.68 25$ Jog k 5.0 ^ 0 ^ U r\ ('}

"PURE” STERIC ENERGY PLOT i u e 3 Figure 1.0 reactivity" relationship is not complete and that some other substituent effect is exerting a significant influence upon the reaction rate.

If the log k values for the seventeen amides studied are plotted against EC a family of straight lines is produced as shown in Figure 3* The lines are parallel i.e. with the same degree of susceptibility to pure steric effects, but are separated by an amount approximately proportional to the number of alpha—hydrogens in the substituent. Thus it is apparent that a Taft equation of the form

log k - log k U = 8 .E° b + h(n-3) ...... (3 )

where n is the number of alpha-hydro gens in the

substituent

and I* is the susceptibility of the reaction series

to hyperconjugative effects should produce an improved correlation over that obtained using the Taft linear steric energy equation. Multiple regression analysis of log k on E and (n-3) gave a significant correlation for all the substituents, and again an improved correlation was obtained by omitting the tert. butyl substituent. The results of the correlations are summarised in Table 5* -An illustration of the increase in precision of equation (3 ) may be obtained TABLE 5

CORRELATIONS USING ’’PURE" STERIC ENERGY PARAMETERS AT 75°C

EQUATION (3) STERIC - HYRERCONJUGATIVE

No* of Substrates 17 l6 +

S 1.111 1.117 h -0.646 -0.564 log k Q -1.162 -1.314

Corr. Co-eff. 0.983 0.993

S.D. 0.104 0.071

Degree of Freedom 14 13 iZ-Test 20.7^ 31.41 Significance Level 0.1# 0.1#

+ Tertiary butyl group omitted*

VARIANCE RATIO F-TEST a) Significance of Improvement due to omission of tert* butyl group.

F = 2.28 Significance Level = lOtfo b) Significance of Improved Correlation given by Equation (3 ) over Equation (l) Significance No. of Substrates F Level

17 3.76 2.5 # 16 3.41 2.5# ST5RIC-HYPERC0WJUG-ATI7E CORRELATION by transposing it to equation (4)

^log k/(n-3) = S *Eg/(n“3) + h . o o o o . . . o o..o.(4) and plotting Alog k/(n-3) against S«EC/(n-3) as in

Figure 4. Comparison of Figure 3 and Figure 4 shows the vastly improved correlation achieved using equation (4) over that obtained using equation (l) and the pure steric substituent parameters. The correlation co-efficient of 0.983 produced by equation (3 ) confirms that a perturbing influence, proportional to the number of alpha­ hydrogens in the amide, is exerting an effect upon the reactivity of the amides towards acidic hydrolysis. If the deviant tertiary butyl group is omitted an excellent correlation co-efficient of 0.993 is obtained.

In correlating structure and reactivity for the dilute acidic hydrolysis of amides it has been possible to correlate reactivity (log k) with the following substituent parameters:-

a) Taft*s Eg parameters i.e. a hybrid steric-

hyperconjugative correlation « c b) Hancock, Yager and ^er»s Eg parameters i.e.

a pure steric correlation

* Manipulation of equation (3 ) into linear form (equation imposes unnecessary constraints upon the data and is therefore used here merely to illustrate the efficiency of the correlation and not to obtain numerical values of the parameters. and c ) an EC , (n-3) correlation i.e. a steric-

hyperconjugative correlation using independently

defined steric and hyperconjugative substituent parameters•

It now remains only to establish which set of parameters produces the best correlation and if the improvement in correlation given by this set of parameters is significant0

Since previous discussion has established the presence of a hyperconjugative perturbation in the hydrolysis it is only necessary to compare the two correlations involving hyperconjugation, i.e. the improvement in correlation produced by the independently defined steric and hyper­ conjugative parameters (correlation c) compared with the correlation given by the normal Taft Eg parameters

(correlation a).

A Variance Ratio F-Test to determine the significance of the improved correlation gave an F factor of 3*^+1

(Table 5) and hence the improved correlation is significant at the 2.5$ level i.e„ the possibility that the improved correlation arose purely by chance is only 1 in 40.

Correlations using a six-parameter equation of the type

(5) log k - log k o i • e an equation considering the polar, steric and hyper- conjugative influences of a substituent upon reactivity, produced marginally improved correlations, but the improvements were statistically insignificant. This is expected however, as only two of the amides have appreciable polar substituent parameters and the effect is as previously indicated, almost negligible.

The structure reactivity correlations above indicate that the dilute acid catalysed hydrolysis of amides is sensitive to at least two substituent effects:-

a) a purely steric influence, and

b) a hyperconjugative perturbation proportional

to the number of alpha-hydrogens in the

sub s t i tuent•

The mechanisms by which the steric effects of substituents influence reactivity are well documented^9 ^ and will not be further discussed here. However, the mechanism of # hyperconjugative control is not as evident.

Mechanism of H y p e r conjugative-Reactivity Interdependence 10 The "classical" mechanism of hyperconjugation i.e. the slight electron releasing property of alpha-hydrogens in an alkyl group, may be considered to influence the reactivity of amides towards dilute acidic hydrolysis by an increased stabilisation of the intermediate amidium ion (Figure 5). 6 /

FIG. 5,

The slight electron shift from the alpha-hydrogen atoms stabilises the amidium ion by reducing the degree of positive charge on the carbonyl carbon atom, thus restricting the ease of nucleophilic addition of water and reducing the hydrolysis rate. This "classical" mechanism involves only a shift of electron density from an alpha-hydrogen, through sigma bonds, to the carbonyl carbon atom and thus it is reasonable to assume that each alpha-hydrogen would exert an equal and independent effecto Since the degree of separation between adjacent members of the family of straight lines in Figure 3 represents the effect on reactivity of the loss of successive alpha-hydro gens it should be equal if each alpha-hydrogen exerts an equal effect. This is not the case and therefore it is unlikely that the hyperconjug- ative stabilisation in the present reaction series occurs via this mechanism Kreevoy and Eyring 20 have suggested that an unsaturated molecule may be stabilised by a direct interaction between alpha-hydrogens and the unsaturated centre i.e. an alpha­ hydrogen bonding. Molecular orbital calculations have shown that each alpha-hydrogen exerts an independent effect, but unlike the "classical" mechanism, the effect of the alpha-hydrogens is unequal. Since the mechanism involves a direct bonding association the first alpha­ hydrogen will have the largest effect as it can assume the most favoured bonding position. The second and third alpha-hydro gens will produce successively smaller effects since there is now competition for the most favourable bonding position. Rotation about the carbon-carbon sigma bond leads to an average stabilisation value when two or more alpha-hydro gens are present.

Stabilisation of the amidium ion by either of the mechanismsdescribed has no counterpart in the transition state and thus the presence of alpha—hydrogens inhibits the acidic hydrolysis in the commonly documented 15,12 order

CH^ > XCH2 > X2CH > X3C

Throughout the discussion attention has been drawn to the deviant nature of the tert. butyl group. The deviation can be explained in two manners: a;\ When Hancock, Yager and Myers c defined pure

steric parameters as

ECs = E s + Oo306(n-3)

they in fact assumed that each alpha—hydro gen

exerts an equal stabilising effect.

b) Structure-reactivity correlations, such as

equation (3)» also assume that each alpha­

hydrogen produces an equal effect.

Both a) and b) are probably incorrect since the alpha­ hydrogen bonding mechanism of hyperconjugation states that the loss in stabilisation involved in losing the final alpha-hydrogen i.e. in passing from the n = 1 to the n = 0 series, is greater than that involved in the loss of either the first or second alpha-hydrogen. To date tert. butylacetamide is the only amide having no alpha—hydrogens for which accurate acidic hydrolysis data is available together with a Taft steric substituent parameter. However, it may be expected that all amides having no alpha—hydrogens would display the same apparent deviation as does tert0 butylacetamide.

The fact that the alpha-hydrogen bond mechanism of hyperconjugation can explain the deviant behaviour of the tert. butyl substituent whereas the "classical" mechanism cannot is strong evidence that the hyperconjug- ative stabilisation of the amidium ion occurs via a direct alpha-hydrogen bond.

Conformational Inhibition of Alpha-Hydrogen Bonding Hyperconjugation Examination of Figure 2 shows that there is considerably greater scatter in the fitting of equation (l) to the data for the amides having one alpha-hydrogen than was found when the same equation was fitted to the data for the n = 2 group of amides (Figure 1). The line of least squares (line A, Figure 2) runs reasonably close to four of the points leaving the iso-butyramide point as the apparently deviant member. The tf alpha-hydro gen bonding” concept of hyperconjugation requires that the alpha­ hydrogens are free to assume conformations in which they can effectively interact with the Tf -electron system of the molecule. This is true for three of the five members of the series, but the alpha-hydrogens in cyclohexane- carboxamide and cyclopentanecarboxamide are clearly

considerably more constricted. An alternative line which passes through the points for the three "conforming” substituents and leaves the cyclic substituents as deviant members is therefore to be preferred (line B, Figure 2).

It is also found that line (b ) is more closely parallel to the n = 2 line than is line (a ) i.e. line (b ) shows, as is to be expected, the same susceptibility to steric effects as was found for the n = 2 series. °c w 0 H G

FIG.6.-AXIAL

o . Baddeley and Gordon 8 , as a result of their study of the hydrolysis rates of 4-alkyldiphenylmethy1 chlorides, have concluded that an interdependence exists between hyperconjugation and conformation i.e. a steric hindrance of hyperconjugation can occur due to conformational changes

The ability of a substituent to affect the hydrolysis rate in this manner was found to be

cyclopentyl cyclohexyl p> iso-butyl i.e. the same order of deviation observed in the present work •

86 Van Bekkum and co-workers , after measuring the

K values of a large number of cyclohexanecarboxylic acids cl have postulated the following conformations for the equatorial and axial carboxyl groups (Figures 6 and 7)* In

Figure 6 the plane of the carboxyl group is parallel to the plane through the axial C^-H and C^-H bonds (Figure 8), while in the equatorial conformer (Figure 7) the carboxyl group eclipses the —H bond# The different orientations of the carboxyl group in Figures 6 and 7, with respect to the C -H bond, implies that the effect of a substituent 1 in the 1-axial position on the 1-equatorial carboxyl group will differ from that of the same substituent in the

1-equatorial position on a 1-axial carboxyl group.

For the specific case of hyperconjugation it has been 8*7 stated that the hyperconjugative effect is maximal when the hydrogens are placed on either side of the plane i«e. with the carbon atom in the plane. This situation

arises in the equatorial conformer (Figure j), which is most stable, and thus the hyperconjugative stabilisation

is maximal in this conformer, but is considerably less in

the axial conformer due to increased conformational stress.

It is reasonable to assume that the amide group will

exhibit conformers similar to those found by Van Bekkum

for carboxylic acids and since monosubstituted cyclohexane

compounds exist in equilibrium mixtures and not exclusively

in one conformation^, then, during the acidic hydrolysis

of eyelohexanecarboxamide, some of the amide will exist in 89 the more reactive axial form, e.g. by Eliel’s. method it . can be calculated that 23 $ of eye lohexane carboxylic acid

exists in the axial conformer at 30°C.^

The axial conformer will thus hydrolyse faster than

the equatorial conformer since the stabilising influence

of the alpha-hydro gen present in the equatorial conformer

is diminished or non-existent in the axial conformer, i.e.

the amide will hydrolyse at a slightly faster overall rate

than expected.

The perturbing effects of the cyclohexyl and

cyclopentyl groups would also be expected to be present m the hydrolysis of esters. Chapman, Shorter and 91 92 co-workers ’ have made an extensive study of the hydrolysis of cyclohexanecarboxylates, in both acidic

and basic media, to assess the importance of the conform­

ation of the methoxycarbonyl group in determining the reactivity of the esters.

A general conclusion of the study was that the methoxycarbonyl group is more stable in the equatorial

conformer and this is in complete agreement with the

results of the present study. In both cases the extra

stability of the equatorial conformer is believed to be

due to an increased alpha-hydro gen bonding stabilisation.

If the perturbing effects of the cyclic substituents were equal in the two reactions i.e. amide and ester

hydrolysis, then no deviations would be expected to

occur in the linear free energy relationships. However,

the majority of the kinetic studies concerning the

hydrolysis of aliphatic esters, from which Taft defined

his substituent constants, have been made at or about -i _ room temperature , while the present amide study was

carried out in the 69—95°^ temperature range. Since high

temperature conditions favour the reactive conformer it is

reasonable to assume that more of the reactive conformer was present during the amide hydrolyses than was the case

in the ester hydrolysis, i.e. the amides hydrolyse faster than predicted by the Taft substituent parameters thus producing deviations in the linear free energy relation­ ships .

A similar explanation would also apply for the cyclopentyl group, but unfortunately this group has not been as extensively studied as has the cyclohexyl group.

The larger magnitude of the effect in cyclopentane carbox­ amide could be attributed to one, or a combination, of the following factors:-

a) the conformational inhibition of alpha-hydrogen

bonding is greater in the cyclopentyl group

than for the cyclohexyl group, or

b) more of the cyclopentanecarboxamide exists in

the reactive conformer than is the case for

cyclohexanecarboxamideo 3

B: DISCUSSION OF THE RESULTS OF THE BASIC HYDROLYSIS — OF AMIDES ' " ' "

The first structure reactivity correlation reported for the dilute basic hydrolysis of aliphatic amides was

that due to Bruylants and Kezdy 2 0 Using the kinetic

data for the hydrolysis of nine alkyl-substituted amides

and the three alpha-chloroacetamides it was shown that a

reasonable correlation was produced by the equation

log k - log kQ = + Es ...... (6)

and a value of /> = 2.7 was reported, i.e. the reactivity

of aliphatic amides undergoing basic hydrolysis is

influenced by a combination of both the polar and steric

effects of the substituents.

The work of Bruylants and Kezdy in basic media

appears to be free of the systematic error involved in

their acid catalysed results and shows general agreement

with results obtained. by other workers# 68

Bruylants and Kezdy1 s use of equation (6) implies a

value of S of unity, i.e. that the basic hydrolysis of

amides exhibits the same susceptibility to the steric

influences of substituents as does the defining ester

hydrolysis. In view of the mechanistic similarity of 97 the two reactions this is a most reasonable assumption; but it is nevertheless, an assumption.

3k Bolton , made a re-examination of Bruylants and

Kezdy*s correlation to determine the validity of the above assumption and to determine if a hyperconjugative perturbation, similar to that noted for the acid catalysed hydrolysis, existed for the alkaline hydrolysis also.

The results of Bolton’s correlation, together with

those of Bruylants and Kezdy are summarised in Table 6.

Bolton found that the Taft four-parameter equation

log k - log kQ = /P • + b .Eg (2)

gave a reasonable correlation for all the substrates

considered.

The value of S = 0.729 obtained by Bolton using equation (2) indicates that Bruylants and Kezdy*s assumption

of S equal to unity is not strictly accurate. However, equation (3)> which attempts to account for polar, steric

and hyperconjugative influences of substituents, gave a

value of S =1.08 which appears to substantiate the assumption of Bruylants and Kezdy. The improved

correlation co-efficient (F = 3*7^, Significance Level = 3fo)

produced by equation (5) over equation (2), together with

the appreciable magnitude of the parameter h, led Bolton 9; TABLE 6

ALKALINE HYDROLYSIS OF AMIDES - TAFT EQUATION ANALYSIS AT 75°C

B ru y 1 a nts & Kezdy B o lto n B o lto n B o lto n E q u a tio n 6 E q u a tio n 2 E q u a tio n 5 E q u a tio n 7

Polar + Steric Polar + Steric Polar + Steric + H»C.J. Polar + "Pure S t e r ic

No. of Substrates 12 12 12 12 s 1.06 0.729 1.081 0 . 5 3 0 p * 2.7 2.087 2.0^9 2.068

h - - -0.7 4 3 -

lo g k + - 2 .83I - 3.126 - 2 . 8 1 2 o

C o r r . Coeff. + 0.987 0.977 0 .956

S.D. + 0 . 2 8 8 0 .149 0.527

Degree of Freedom + 9 8 9 O O • t-Te s t + 19.41 42.27 to

Significance Level + 0 . 1 # 0 . 1 # 0 . 1 #

+ Not available to conclude that the hyperconjugative stabilisation of

the amide by alpha-« hydro gens in the substituent was approximately as effective in the basic hydrolysis as in

the acidic hydrolysis•

Preliminary kinetic runs on acetamide in basic media to determine the applicability of the experimental

techniques used earlier for the acidic hydrolysis produced

results which were in general agreement with those of

Bruylants and co-workers 2 , but which were more closely

aligned with the later work of Packer, Thomson and vr ,68 Vaughan •

Table 7 compares the kinetic data for the basic

hydrolysis of acetamide at 75°C obtained in the present

project with that of the abovementioned workers. Since

Packer and co-workers had studied only four amides it

was considered advantageous to re-examine the amides

studied by Bruylants and co-workers.

TABLE 7

Results for the Hydrolysis of Acetamide in Dilute Alkali at 75°C ------“ “ ' ~ ~ 2 ~ Pac^er anc^68 Present Bruylants Co-workers Work

q 1 ■■ 1 k xlC) (1 .mole- sec" ) 1.13 1.50 i •36(¿0.oi) + / _ — 1 \ A H (cal.mole ) 13^79 13511 13217(- 6 0 ) AS (cal.deg. mole ) - 33-6 -33.0 -33.9(-0.2) Ido In addition to this several highly substituted amides were investigated so as to obtain a maximum variation of both the hyperconjugative perturbation and the steric influences in the series and hence fully test Bolton’s proposed hyperconjugative stabilisation of the amide in basic media.

The results for the hydrolysis of thirteen aliphatic amides in basic media were compiled and subjected to

structure-reactivity correlations similar to those made by

Bolton. The results of the correlations are summarised

in Table 8.

For the thirteen amides studied the Taft four- parameter equation (equation 2) gave, as indicated by

the student’s t-test, a significant correlation, i.e. reactivity is closely related to a combination of polar

and steric influences of the substituents. However,

again the relationship is not complete as is indicated by the even more significant correlations obtained when

the amides are separated into series in which the hyper—

conjugative influence of the substituents are maintained

constant, i.e. as in the acid hydrolysis a hyperconjugative perturbation proportional to the number of alpha—hydro gens is affecting the hydrolysiso

To quantitatively assess the role of hyperconjugation,

correlations were made using the equations 101

TABLE 8

ALKALINE HYDROLYSIS OF AMIDES - TAFT EQUATION ANALYSIS AT 75°C

Equa t i on 2 Equation 2 Equation 2 Polar-Steric Polar-Steric Polar-Steric

"4" , * No. of Substrates 13 7 k s 0.506 0.985 0.943

1.460 lo703 0.662 log k - - ° o -2.779 2.636 2.561

Corr. Co-eff. 0.912 0.996 0.988

S.D. 0.202 0.054 0.039

Degree of* Freedom 10 k 1 t-Te s t 7.3 6 24.91 9.04

Significance Level 0.1# 0.1# 0.1#

+ Substituents with two alpha-hydrogens

* Substituents with one alpha-hydrogen log k - log k = 0*0-* + $ . EC ...... (7) O / S and log k - log kQ - ? - ■ * * * £ .E® + h(n-3) ..... (5) in which the steric influences of the substituents are Q represented by the pure steric Eg substituent parameters.

The results of the correlations are summarised in Table 9*

Examination of the correlations indicated the presence of a deviant substrate viz. the tert. butyl substituent.

This was omitted and the correlations repeated for the remaining twelve amides. The results are summarised in

Table 9.

Equation (7) i«e. the pure steric-polar correlation,

gives, as indicated by the Student*s t—test, a significant

correlation, but again the correlation—co—efficient is poor,

indicating that another substituent effect (as yet

unconsidered) is exerting a significant effect. The

greatly improved correlation produced by equation (5)

(F = 18.5, Significance Level = 0.1$) shows that the

perturbing influence indicated by equation (7) is

proportional to the number of alpha-hydrogens in the

substituent, i.e. is similar to the alpha- hydrogen

bonding effect previously noted for the acidic hydrolysis

of aliphatic amides.

The value of the parameter h, the susceptibility of

the reaction series to hyperconjugative effects, of -0.573 1 0 TABLE 9

ALKALINE HYDROLYSIS OF AMIDES - TAFT EQUATION ANALYSIS AT 75°C

Equation 7 Equation 5 Pure Steric-Polar Pure Steric-Polar- H.C.J.

No, of Substrates 13 12 13 12 & 0.252 0.447 0.867 0.985 e * 1.595 1.544 1.716 1.668 h - - -0.608 -0.573 log k -2.814 - - o -2o669 1.198 1.176 Corr. Co-eff, 0.870 0 o900 0.975 0.994

SoDo 0.243 0.217 0.111 0.053

Degree of* Freedom 10 9 9 8

t-Test 5.86 6.52 14.58 28.68

Significance Level 0.1$ 0.1$ 0.1 $ 0.1$

VARIANCE RATIO F-TEST Indication of the Significance of the Improved Correlation given by Equation (5) over Equation (7)- __ No. of Substrates F Significance Level

13 4.86 1$ 12 18.50 0 .1$ for the basic hydrolysis compared with h = — 0*582 for the acidic hydrolysis, indicates that the hyperconjugative stabilisation of the amide with respect to the transition state has approximately the same effect under both sets of reaction conditions*

As in the case of the acidic hydrolysis, the mechanism of the hyperconjugative stabilisation can be simply explained in terms of Kreevoy and Eyring’s alpha­ hydrogen bonding model. Each alpha-hydrogen is, by means of a direct bonding interaction with the TT -electron system, able to lower the potential energy of the amide 3 reactant with respect to the sp transition state, in which no such stabilisation is possible, thereby increasing

the free energy of activation and retarding the hydrolysis rate •

As in the case of the acidic hydrolysis, the tert butyl group displays deviant behaviour. However, this is

only to be expected since the respective correlations have shown that the magnitude of the hyperconjugative perturbation is similar in both acidic and basic media

e.g. at 75°C - hacidic = 0,582 ‘'basic = 0,575

In view of this it is expected that, not only will the

tert. butyl group be deviant, but that it will display

the same degree of deviation in both media. This is in fact found to be the case as shown in Table 10. 1.4

1.3

1.2

- Alog k Es

1*1

1.0

0.1 0 .2 0 .3

" > ‘/S S 106 TABLE 10

Analysis of the Deviant Nature of the Tertiary Butyl Group at 75 C

Acidic Basic

•4 -4 k^ experimental 2.256 X 10 2.542 X 10 k^ predicted by Eqn. (5) 1.300 X 10“ 1.435 X 10“ ^ .4 Difference 0.956 X 10" 1.107 X io"4

Percentage Deviation 42.5 43.5

In the acidic hydrolysis of amides a conformational inhibition of hyperconjugation was noted for the cyclic amides in the n = 1 series. Since the hyperconjugative stabilisation effect has been shown to be equally effective in basic media, the same conformational inhibition should be evident in the basic hydrolysis of the cyclic n = 1 amides. Unfortunately kinetic data for only four n = 1 amides are available in basic media viz. two cyclic and two "conforming" substituents. However, by transposing the Taft four-parameter equation

^ - log k - log kQ = + 6 .Eg to A 1 og k/Eg = y?* cr*/Es + £ and plotting ¿U°g k/Eg against Eg for the amides available the deviant nature of the cyclic amides can be illustrated (Figure 9)* Insufficient data are available 107 to allow the magnitudes of* the deviations of* the cyclic members to be calculated since the remaining two points are insufficient to define the plane of reference. As in the case of the acid hydrolysis, however, the deviation is 85 seen to increase in the accepted order.

i.e. cyclopentyl > cyclohexyl > iso butyl C: ANALYSIS OF THE TAFT SUBSTITUENT PARAMETERS IN TERMS OF THE HYDROLYSIS OF AMIDES

One of the principal difficulties faced by Taft1

in establishing his scale of substituent parameters for

aliphatic reactivities was the absence of a complete set

of rate data obtained under consistent conditions for the

acidic and basic hydrolyses of esters. In order to produce , * an extensive list of Cr and Eg values Taft was obliged

to use data which departed drastically from the ideality

of the reaction system in which the parameters were

defined. These departures from ideality of definition

fall into three main areas

i) data from esterification reactions as well as

the defining hydrolysis reaction were used. This

was justified by Taft in terms of the similarity

of the transition states of the two processes.

ii) the esters used, RCOOR , had variations in the

R1 group as well as the R group

iii) data obtained from studies in a variety of organic

and mixed aqueous/organic solvents had to be used.

The justification advanced for the last two points was that the log (k/k ) and log (k/k ) values did not O X I . 109 appear to vary very much with either solvent or the nature 1 oi R . Where data from more than one of these sources existed Taft averaged the log (k/k ) values to obtain the listed parameters.

All aqueous organic solvents can, in principle at least, show specific solvation interactions between the organic component and the reactant molecules. For this reason water is clearly the ideal solvent in which to study a hydrolysis reaction. The low solubility of most esters in water makes the study of their hydrolyses in aqueous solution difficult, if not impossible, and all of the rate data used by Taft came from studies in aqueous organic solvents. Taft noted however, that for the few esters for which studies in aqueous solution had been made the log (k/kQ) values differed somewhat from those obtained in aqueous organic solvents for the same 2 substituents. This is perhaps, in keeping with Shorter’s criticism that Taft’s assumption, that steric effects are the same in both the acidic and basic hydrolysis, neglects possible differences in the role of the solvent due to the opposite charges of the transition states.

With all these apparently justifiable criticisms levelled at it, it is perhaps surprising that the Taft approach enjoys any success at all. The very large body of both reactivity and non-reactivity data that the Taft n o parameters are able to correlate, supplies fairly convincing evidence that the separation of polar and steric effects claimed by Taft, is, for the most part at least, achieved.

The hydrolysis of amides is a reaction which is mechanistically identical with the hydrolysis of esters, but in which the ideality of the Taft approach can be completely maintained. Since the present work contains rate data for the acidic hydrolysis of 17 amides and the basic hydrolysis of 13 amides all in aqueous solution and throughout these reaction series only the R component in

RCONH^ was varied thiBsedata can be used to define steric and polar substituent parameters on the amide scale (a ) from the expressions:-

log (k/ko )a and

whore k refers to the hydrolysis of acetamide and o the subscripts a and b refer to the acidic and basic

hydrolyses, respectively, of the substituted amides.

. ^ . 1 Table 11 summarises the Taft substituent constants used in the present study together with the corresponding substituent constants defined on the amide scale. 3 T f

T A B L E 11

SUBSTITUENT CONSTANTS IN TERMS OF ESTER AND AMIDE HYDROLYSIS

Taft Sub s t i tuent Cons tant s A m i d e Substituent C o n s t a n t s R i n R C O N H 2 -,- E * E" (e )a s < r s v s' _____

c h 3 - 0.00 0.00 0.00 0.0 0 0.00 0.00

- - - o . o 4 - 0.22 C 2H 5- - 0.07 0.10 0.38 0.0 9 n - C 3H 7 - - 0.36 - 0.115 - 0.67 - 0 . 2 4 - 0.03 -0 . 5 5

-0 . 5 4 ü - C 4H 9 - - 0 . 3 9 - 0.13 - 0.70 - 0.23 - 0.07 i s o - C ^ - -o. 47 - 0.19 - 1 . 0 8 - 0 .23 - 0 . o4 -0.84

i s o - C 4H 9 - - 0 . 9 3 - 0.125 - 1 . 2 4 - 0.92 0.02 -1.21

t e r t - C ^ - -1 . 5 4 - 0.30 - 2 . 4 6 — 0.66 - 0.03 -1 . 6 5

tert-C^H^CH^- - 1 . 7 ^ - 0.165 - 2.05 - 1.72 - - 2.03

B r C H 2 - - O o 27 1.00 - 0 . 5 8 o.o4 - -O .27

c i c h 2- -o„ 24 1.05 - 0.55 0.07 - - 0 . 2 4

c 6 h 1 1 c h 2- - 0 . 9 8 - 0.06 - 1.29 - 0.92 0.01 - 1.23

c h 3 o c h 2- - 0.19 0.50 - 0.50 - 0.06 0.4 0 - 0.37

(c 2h 5 )2 c h - - 1 . 9 8 - 0.225 - 2.59 - 1.76 - - 2.37

C 0H e . CH . CH — - 0.210 - 1.74 - 0 . 8 2 - 0 . o4 - 1.43 2 5 3 - 1 . 1 3 eyelo-CIi - - 0 . 5 1 - 0.20 - 1 . 1 2 -O.O 5 - 0.09 -0.66 5 9 cyclo-C^H,„ — - - 1 .4o - 0 . 4 2 - 0.05 -L .03 — z ---- 6 -|-j - 0 . 7 9 0.15 00 CO 0 1 • 0.215 - 0.69 -O .25 0 . i4 - 0.56 C 6 H 5 C H 2- tert ^ — (— 2.92 ) + - - 3 . 8 4 - 2 . 2 4 - - 3.16

+ Calculated Value from Fig. 1 112 Figure__10

STERIC ESTBR/AKTDB CORRELATION 113 Steric Substituent Constants

To determine the degree of correlation between the two sets of steric parameters in Table 11 a plot of E versus s (Es) was made (Figure 10). The familiar family of straight lines produced is not unexpected since this plot differs from the E^ versus log k plot (Figure 3 on page to) only in that the log k values have been divided by a constant (the rate constant for the hydrolysis of acetamide in dilute acid at 75°C) to produce the (E values, S

A statistical examination of Figure 10 indicates

that the correlation between E and (E ) is highly s s significant (t = 10.33> significance level = 0.1^) while

the poor correlation co-efficient (r = 0,935) indicates

the presence of a perturbing influence. Inspection of

Figure 10 reveals that the perturbation is hyperconjugative

in nature, i.e. propotional to the number of alpha­ hydrogens in the ester and amide. To determine the

significance of the hyperconjugative perturbation correl­

ations were made between

a) E and (E )A substituent constants for substrates s s with two alpha-hydrogens, and

b) E and (E )A substituent constants for substrates ' s v s 7 with one alpha-hydro gen.

A summary of the results of these correlations appears in

Table / 2. 114

T A B L E 12

ESTER/AMIDE SUBSTITUENT PARAMETER CORRELATIONS

Correlation e s /( e s )a E / ( E )A E / ( E )A E° / (e s )a s x s ' s v s ' s ' v c ' n = 2 A m i d e s n = l Amides

No . of“ S u b s t r a t e s 17 8 5 17 15 13 12

Correlation Co—elf. 0 . 9 3 5 0.9 9 9 0.993 0.959 0. 9 8 6 0.939 0.965

Stand. • D e v i a t i o n 0 . 2 1 1 0 . 0 2 2 0.074 0.209 0.1 1 8 0.073 0.055

’t— T e s t to 1 0 . 2 3 9 6 1 . 7 4 3 14.3 4 4 1 3 . 0 8 8 2 0 . 9 9 6 9 . o4i 11 * 566

D e g s . of F r e e d o m 15 6 3 15 13 ll 10 H O Significance Level o.i $ o.i $ 0 . 1 $ 0 . 1 $ 0 . 1 $ 0 .1$ •

TABLE 13

STABILISATION ENERGIES PER ALPHA-HYDROGEN AT 75°C

No. of Alpha—Hydrogens Family Separation (cals.) Effective No. of Alpha.—Hydrogens

O 0 O

1 I 6OO 2

2 2400 3 4 3 32OO 115 The excellent correlations obtained for the amide

families in -which the number of alpha-hydro gens is

constant, compared to the correlation obtained for all

the amides, illustrates the existence of a hyperconjugative perturbation in both the hydrolysis of esters and amides0

Thus, in order to correlate the steric parameters defined

in terms of esters with those defined in terms of amides

for all the amides studied, a "pure steric" correlation must be made i.e. E° versus (E0 )^. s v s '

84 Hancock, Yager and Myers3 have removed the hyper-

conjugative influence from Taft’s steric parameters by use of the expression

Ecs = E s + 0 .3 0 6 (n-3) ...... (8 )

However, the factor 0 •306, representing the "bonding

effect" for one alpha-hydrogen, applies only to the

hydrolysis of esters at 35 C. In order to calculate

(EC )A values, iGe. pure steric parameters defined as above,

but in terms of the hydrolysis of amides, it will be necessary to make a similar Molecular Orbital calculation based on an amide molecule instead of an ester.

Since the results of such a calculation are unavailable

at present it can be assumed that, as a rough approximation,

the factor used by Hancock, Yager and l^ers to calculate

jr;c values for esters is also valid for amides. Table 11 s summarises the (EC )^ values calculated using equation (8 ). s 116 Figure 11

"FORE" STERIC BSTER/AMIDE TORRTüT.flncflf 117 c / c \ A . A plot of E versus (E ) is shown in Figure 11. s s The correlation co-efficient of 0.959 and related statistical tests (t = 13*09, significance level = 0.1$) indicate a good linear correlation for all the amides studied. Previous discussion has shown that two substituents i.e. the tertiary butyl and cyclopentyl groups, exhibit deviant behaviour from the Hancock, Yager and Myers model. If these substituents are omitted the correlation is excellent i.e. correlation co-efficient =

0.986, t = 20.99, significance level = 0.1$. A complete summary of these correlations is shown in Table 12.

In view of the excellent linear plot obtained when

Eg is plotted against (Eg)^ it appears that the assumption made in defining (E ) i.e. that the Molecular Orbital factor representing the degree of alpha-hydrogen bonding per alpha-hydrogen for esters at 35°0 is similar to that for amides at 75°0, is a reasonable assumption.

The present study included the hydrolysis of

2•2—dimethyIbutyramide in dilute acid. The tertiary pentyl substituent involved has no recorded Taft parameters, but by using the acidic hydrolysis data for the amide an

(E )A value of -2.24 was calculated« Since the tertiary v s 7 pentyl group has no alpha—hydrogens the n = 0 line of

Figure 10 can be utilised to give a corresponding Taft steric parameter of Eg = -2.92. 118

Kreevoy and Eyring * s explanation of hyperconjugation in terms of alpha-hydrogen bonding predicts a decrease in the stabilisation produced by each alpha-hydrogen after the first. This is in direct contrast to Hancock, Yager and 84 , . . c Myers who, m their definition of E values, assume an s ’ equal effect from each alpha-hydrogen. The results of the present work substantiate the views of Kreevoy and

Eyring as is evidenced by the unequal separations between the lines in Figure 10 and in Figure 3 (page So) „

If the separation between the lines in Figure 3 is taken as a direct measurement of the stabilisation produced by the addition of successive alpha-hydrogens then, as shown in Table 13, the "effective number of alpha-hydrogens" is one more than the number of alpha­ hydrogens in the amide since the first alpha-hydrogen has twice the stabilising capacity of each of the other two, i.e. since the second and third alpha-hydrogens each produce a stabilisation of ^800 calories at 75°C this is taken as the unit of stabilisation per alpha-hydrogen and the "effective number of alpha-hydrogens" is given by

EN = total stabilisation/800 calories, ot

Polar Substituent Constants Correlations between the Taft parameters and the corresponding parameters defined in terms of amide hydrolysis d"are less complicated than those for the 0.6 „ 119 Figure 12 POLAR ESTER/AMIDB CORBy.T.ATTfw

- 0.2 120 steric parameters since they are calculated as a difference between the basic and acidic hydrolyses and most small specific effects in any one amide tend to cancel out. On the other hand the wide variation in the magnitude of the parameters noted for the steric correlations is absent since most of the substituents considered have only small polar substituent constants.

A plot of q versus (f~^ (Figure 12) for all the amides has only a poor correlation-co-efficient of 0.939» but this improves to 0.9^3 if the ever deviant tertiary butyl group is omitted. Both correlations are highly significant however, giving Student!s t-test numbers of

9.0^ and 11.37 respectively, i.e. both correlations are significant at the 0.1^ level. A detailed analysis of the correlation is shown in Table 12.

The correlations made above have shown that an excellent correlation exists for the Taft substituent parameters defined in terms of ester hydrolysis and the corresponding substituent parameters defined in terms of amide hydrolysis. Since the amide hydrolyses were carried out under consistent conditions this may be taken as further evidence that the assumptions made by Taft in defining Eg and parameters appear to be reasonably well justified. 121 Figure 13a ACIDIC ISO-KINETIC CORRELATION

AS* Kcal

16

* ^ A H x 1CT cals,

Figure 1Jb 122

D: EXTRATHERMODYNAMIC RELATIONSHIPS

Any discussion of the influence of molecular structure

on enthalpies and entropies of activation must always be

obscured by the relatively large and inevitable errors of measurement of these quantities. Such discussion is

further complicated, in the present study, by the number

of different experimental techniques necessary to study

such a wide range of compounds giving rise to greatly varying experimental errors for the various amides.

Table l4 summarises the thermodynamic parameters

obtained from the hydrolysis of the amides of the present

study in both acidic and basic media. Entropies of activation are calculated at 75°C*

For both the acidic and basic hydrolyses of aliphatic amides roughly linear plots of enthalpy versus entropy were obtained (Figures /3ct ) indicating possible g iso-kinetic relationships. However, Petersen has shown that such a linear plot is insufficient evidence to justify an iso—kinetic relationship and that, if such a relationship exists, plots of log versus for each amide should be concurrent. Inspection of Figures shows that this is not the case, even for a few of the amides in each 123

T A B L E \ b

SUMMARY OF THERMODYNAMIC PARAMETERS AT 75°C

* -1 - * -1 -1 /\11 in cal.mole , Za S m cal. deg. m o l e 1 0 H AMIDE A C I Q BAS I c If „ * Z^H* Z^s Z i H *

ACETAMIDE 1 9 3 5 7 ( - 2 7 5) - 16 .9 (¿0 .8 ) 1 3 2 1 7 (i 60 ) — 33. 9 (¿0 .2 )

PROPANAMIDE 1 7 9 3 4 ( - 1 7 6 ) - 20.7 (¿0 .5 ) 1 4 7 4 2 ( ¿ 1 2 5 ) - 2 9 .7 (¿0 .4)

BUTAN AMIDE 18683(^352) —20.0(¿1•O) 14050(¿154) - 3 2 .9 (¿0.4)

VALERAMIDE I 8665(1337 ) — 20 0 O( ¿ 1 . O ) 14 4 8 5 (¿1 6 8 ) - 3 2 .1 (¿0 .5)

ISO-VALERAMIDE 194l5(i 98) - 2 0 . 9 (-O. 3) 17370(¿688) - 2 5 . 9 (¿ 1 .9 )

3.3.DIMETHYLBUTANAMIDE 2059^(^313) -2i.3(io«9) - -

PHENYL A CETAMIDE 1744o(il39) - 2 3 .6 ( ¿ o „ 4) 11774(¿l33) -39 <^(¿0.4)

CHLOROACETAMIDE 18586(¿318) —18.8(¿0.9) - _ -

BROMOACETAMIDE 18518(¿312) - 1 9 .2(¿0 0 9) - -

METHOXYACETAMIDE 18950(¿280) — 1 8 . 4 ( ¿ 0 .8) 1 3 4 3 1 (i 44) — 2 9 •0 (¿O.1 )

ISO-BUTANAMIDE 194 5 ^(¿1^9) -17.7(¿0.4) 1 3 0 3 1 (¿147) - 36 .o ( ¿0.4)

DIETHYLACETAMIDE 2 1 9 4 6 ^ 3 1 0 ) -17.6(¿0.9) - -

\B METHYLBUTANAMIDE 20798(¿351) - l 6 .5 (il.o) 1 5 3 4 1 (¿638 ) — 32 .O(¿1 .8 )

CYCLOHEXYLACETAMIDE 20833(¿385) - l 6 .9 (il.o) 16457(i 48) —28.7(¿O.1)

CYCLOHEXANECARBOXAMIDE 20228(¿436) - 1 6 .3 (¿ 1 .2 ) 12807(¿117) -37.6(¿0.3)

CYCLOPENTANECARBOXAMIDE 14409(¿175) - 3 1 . 4 ( ¿ 0 .5) 15 2 1 0 (¿3 7 9 ) - 2 9 . 4 ^ 1 . l)

TRIMETHYACETAMIDE 19895(- 95) - 1 8 . 4 ( ¿ 0 .3 ) 16 9 9 2 (¿1 1 3 ) - 2 6 .5 (¿0 .3 )

X.X .DIMETHYLBUTANAMIDE 29573(¿430) 2 . 2 ( i l . 2 ) - - 124 Figure_ 14a

-log(k/T)

-log(k/T) 125 Figure.15

16 23 series, and hence no iso-kinetic relationships are evident

For the acidic hydrolysis of amides the result of * plotting A H against the steric parameter E for the s amides of the present series is shown in Figure /£. The

A e r i z s s / 4^1 + yortioai length of each line represents - 1 standard error of measurement of and the line of regression was calculated by least squares techniques, but with each point given a weight inversely proportional to the

•X- . standard error in A H . A Student*s t-test (t = 5.30,

Degree of Freedom = l4) shows this plot to have a significance at the 0 .1^ level, indicating a definite dependence of A H on E . Cyclopentane carboxamide lies S further from the regression line than can be reasonably attributed to experimental error and has been omitted from the regression analysis. It appears that for this amide some factor, the source of which is not apparent at this stage, varies the enthalpy component of the free energy charge in a way different to that of the other members of the reaction series®

No corresponding correlation was found for the thermodynamic data in alkaline solution, but this could be due to the added influence of the polar effects of the substituents on A h in basic media. 127

It was found that any correlations involving the entropy changes in both acidic and basic media are too obscured by the errors of measurement to yield meaningful results. 128

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50. DUPFY, J.A. and J. Chem. Soc., i960, 545 and 843. LEISTEN, J.A.

51. REID, E.E. J. Am. Chem. Soc., 1900, 24, 397.

52. HINE, J. ’’Physical Organic Chemistry”, 2nd ed (McGraw-Hill, New York, 1962) pp.291-2

53. BENDER, M.L. J. Am. Chem. Soc., 1951, 73, 1626.

54. BENDER, M.L. and J. Am. Chem. Soc., 1955, 77, 348. GINGER, R.D.

55. SWAIN, C.G. Talk before the l44th Meeting of the American Chemical Society, Los Angeles, March 31st-April 5th, 1963.

56. BRESLOW, R. Tetrahedron Letters, 1964, 399.

57. SCHOWEN, R.L., Tetrahedron Letters, 1966(5 ), 497« J AYARAMAN, H • and KERSHNER, L.

58. NEWMAN, M.S. J. Am. Chem. Soc., 1950, 72, 4783.

59. BRUYLANTS, A.A. and Bull. Soc. Chim. Belg., i960, 69, KEZDY, F. 602.

6 0 . BR0¥N, H. J. Am. Chem. Soc., 1938, 60, 1325.

6l . PHILBROOK, G.E. j. Org. Chem., 1954, 19, 623.

6 2 . NATELSON, S. and J. Am. Chem. Soc., 1939, 6l, 970. GOTHFRIED, S.P. Org. Synth., 1941, Coll. Vo.l, 153- 63. JACOBS, W.A. and HEIDELBERGER, M. 132 0\ 0 "Dictionary oT Organic Compounds", Vol.I-V, 4th edition (Eyre and Spottiswoode, London, 1965)*

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66 . FOLIN, 0. and J ♦ Biol. Chem., 1912, ll(5'). 493. FARMER, C.J.

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69. WILLEMS, M. and Bull. Soc. chim. Belges, 1951» BRUYLANTS, A.A. 6b, 191.

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71. SOUNDARARAJAN, S. and VOLD, M.J. Proc. Ind. Acad. Sei., 1957, 46, 303

72. MAZZUCATO, Vo, Annali Di Chimica, i960, 50, 521. FOFFANI, A. and CAUZZO, G.

73. BRUYLANTS, A. A. and Bull« Soc. Chim« Belg., 1959» 6 8 , KEZDY, Fo 225 °

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7 8 . GOOD, M.L. , Spectrochimica Acta, 1967 » 23A, SIDDALL, T.H. and 11 6 1 . WILHITE, R.N. 133 79. EDWARD, J.T. and J. Chem. Soc., 1957, 2000. MEACOCK, S.C.R. 00 O • KATRITZKY, A.R., Tetrahedron, 1963. 19. 463. WARING, A.J. and YATES, K. 00 H • KOLTHOFF, I.M. and "pH and Electrode Titrations", LAITINEN, H.A. 2nd edn0, p.159 (John Wiley: New York). 00 C\i • TALVIK, I. and Reaktso Sposobnost Org. Soedin«, HEINLOO, M. Tartu. Gros. Univ., 1966, 3(l), 244. “ 00 • CROCKER, J.C. J. Chem. Soc., 1907, 91, 593. 00 • HANCOCK, C.K., J. Am. Chem. Soc., 1961, 8 3 , 4211 M^ERS, E.A. and YAGER, B.J.

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ACKNOWLEDGEMENTS

The author would like to gratefully acknowledge

the award of a Commonwealth Postgraduate Scholarship

during the tenure of which this work was carried out*

The author is deeply indebted to Dr. P. D. Bolton

for suggesting the general outline of the investigation

and for his tireless and invaluable consultation during

the course of the investigation.

Thanks are also due to Dr. E. Kokot and Mr. W. Hannan

for their supervision of the investigation during

Dr. BoIton 1s absence.

Finally, it gives the author pleasure to thank

Assoc. Professor E. Gellert for his general assistance

during the investigation; the technical staff for their ready assistance at all times and Mr0 G. Holby for his assistance in preparing the thesis. 135 136

COMPUTER PROGRAMS

Tbe majority of c ai etilati oils and all the regression

analyses required for the present work were performed on

the 6OK I.B.M. 1620 Computer System installed at the

College. Programs were written in Fortran II and a

brief description and listing of the major programs used appears below.

Pro gram 1 .

Experimental results, obtained by using the potentiometric,

conductometric and cation-exchange techniques, were

processed using this program. The program evaluates rate

constants by the use of one of the following equations: -

i) kt = 1 In B(A - x) A - B A (B - x)

i.e. a second order, two component system with the initial

concentrations of the reactants different.

2) kt = x A (A - x)

i.e. a second order, two component system with the reactants

initially at equal concentrations.

1 3) F . kt = (A - é.) ~ x (A - A z 2 Where F 1 (2A + A) (2A + A 137

A = B A i.e. a small difference in concentrations and A_^ __ the final value of A measured. i.e. a second order, two component system in which, the initial concentration of the reactants differ by a small amount.

In the above rate equations the standard symbols

employed have the usual meanings

i.e. A and B = initial concentrations of the reactants

x = concentration of product at time t

t = time

k = rate constant

After reading in experimental data, consisting of

concentration/time pairs, the program calculates the

following:-

a) a rate constant at each experimental time.

b) an average rate constant for the reaction.

c) a least squares (standard regression) rate constant

for the reaction. j g standard deviation from the mean rate constant,

e) a correlation co-efficient indicating the degree of

fit of the points to a straight line. A co-efficient

of unity is perfect and co-efficients greater than

about 0.98 are acceptable. the percentage of the reaction followed. f) 138 Program 2 .

This is a general program which calculates rate constants

Tor second order, two component systems in which resistance

measurements have been used to follow the kinetics. For

systems in which the initial concentrations of the reactants are equal the equation is

( I. - 1 Ì kt = 1 . V. RO RT J A ( 1 - 1 \ V RT RI J where A = the initial concentration of the reactants

RI = the resistance at infinite time

RO = the initial resistance of the reaction mixtur

RT = the resistance at time t.

When experimental data, consisting of resistance/time pairs,

are read into the program a set of results, similar to

those obtained from the previous program, is produced.

If a physical property of a solution is to be of use

in studying the kinetics of a reaction it should vary linearly with time. However, a plot of resistance versus time is curved in the latter stages of the reaction.

This curvature is due to difficulties encountered in measuring accurate values of resistance at "infinite

time”. A subroutine is included in this program which varies RI by small increments until it finds a value which 139 makes the standard deviation of the rate constants from the mean minimal.

The subroutine is justified for the following reasons

1) the curvature is considered to be due not to effects of side-reactions nor to a change in order of the reaction, but merely to experimental difficulties in measuring RI.

2) RI values selected by the computer agree closely with those obtained by measuring the resistance of solutions which have compositions similar to a reaction mixture at 100$ reaction.

3) values of rate constants obtained using the subroutine show excellent agreement with rate constants obtained using other methods, e.g. the potentiometric titration technique.

For systems in which the initial concentrations of the reactants are unequal rate constants can be calculated from resistance/time pairs by use of the following equation:-

kt = 1 In ( ^ r - ~ - s r A-B ("5T" K0 ) ("S t

A similar "variable infinity" subroutine has been incorporated in this program and give s results in excellent agreement with, those obtained by other methods. However, this equation has not had the extensive use and cross­ checking with other methods as has the equation in which the reactants are at equal concentrations.

Program 3

This is a general program to calculate thermodynamic parameters from rate constant/temperature data.

Enthalpies and entropies of activation were calculated by use of the following equation: -

A least squares regression analysis of log f k\ on I \ T ) T gives the enthalpy from the slope of the regression line and the entropy from the intercept of the regression * line with the axis. Values of i.e. the free energy of activation, are then calculated using the expression

= A n - T/\S*

An error analysis is also performed on the thermodynamic parameters as calculated from equation 1. The thermo­ dynamic parameters AS*, E and A are also calculated by use of the Arrehius equation and the results obtained from the two methods were found to be in excellent agreement• 141 Regression Analysis involving the Taft Equations.

Standard programs were available in which the Taft equations

A log k = Polar Energy Equation

A log k = Steric Energy Equation

A l o g k = * S £s 4-Parameter Equation and equations1 of the type

A log k = £ ■ Es and /\ log k = s £s * r h(n-z) were fitted to the data in order to determine which equation i.e. combination of substituent effects, gave the best correlation for the reaction series. These programs calculate statistical data e.g. variances, correlation co-efficient standard deviation etc., which are used to determine the significance of the correlations produced by the various equations. o o o r> o o o 333 2 201 777 177 113 Al 00 81 V / / V 70 2A 28 20 25 11 13 KJ 7 DI MENSI ON TIME(AC), CONC (AC ),RK(AC), CRK(AC),X(AC), Y (AC) READ 200 FORMAT ) / / / / ( READ 11,AO,BO,TNORM R N 81PRINT E D 1AI • .TIME(I),TITN READ 20 READ 177,VFAC,IORD READ 11.ALIQ C ORR =0S =0 SUM=C. . c SD=C. = c FORMAT(5OH AN=N FORMAT(/) K ( )Ÿl ) RK/T I )=Ÿ(l (I ME ) (I O O . GO 7 TO K ( )*( )*VFACRK )=*K(l (l I=1 ,ACDO 7 ) FORMAT (F10.3,M FORMAT ) (AF10 .3 PRINT Al PRINT 200 PRINT Al X ) (I=TI ME I ) ( SRSQ=SRSQ+RK I ( CONC )=TITN*TNORM/ALIQ (I O 1 =,N , 1=1,N DO 21 171GO TO SUM=SUM4RK(l ) (777,777,778),IORD GO TO SRSQ=C. =TI ME( I)*6C. TIME(I) CONC )=>BO-(TITN*TNORM)/ALIQ (I FORMAT(6F10.3) Y )=CONC(l(I )/(BO*(BO-CONC ) ) ) (I ' "(AO-BO)*LOGF l l Y ) (I ( (BO*(AO-CONC (AO*(BO-CONC )(I) )/ ( I ) )) ) N = l-1 O O (2A.25.2A),IORD GO TO IF (TIME 28 ))70,28, (I IF (AO )201,201,113 NGTV TM I REQUIRED NEGATIVE IS ONA TIME THE LAST DATA CARD H R DATATHIRD CARD CONTAINS SECOND ALIQUOT DATA CARD CONTAINS BO AO TNORM IT DATA CARDFIFTH BEGINS TIME-TITRATION PAIRS FOURTH DATA CARD CONTAINS VOLUME CORRECTION DATA CARDFIRST FACTOR CONTAINS IDENTIFICATION F OC CONCENTRATIONS AO=CIF OF REACTANTS ARE EQUAL

...... PROGRAMME - - 1 )**2

142

RK (I ) =Y (l ) /T I ME ( I ) RK( I )^ K (l )*VFAC SRSQ=SRSQ+RK(I)**2 X (I ) =TIME (I ) 21 SUM=SUM+RK ( I ) GO TO 171 778 DEL^BSF (BO-AO) F=1.-DEL*DEL/((2.*AO+DEL)*(2.*(AO-CONC(N))+DEL)) DO 15 I =1,N Z=1 /((AO+DEL/2 )-CONC(l)) -1. / (AO +DEL/2. ) RK ( 1 )=Z/ (F*TIME ( I ) ) RK O )=*K(l )*VFAC ...... SRSQ=SRSQ+RK(l )**2 Y ( I )=1. / (AO+DEL/2. -CONO (l )) ...... X(l ) =TI ME (I ) 15 SUM=SUM+RK(I ) 171 AVE =SUM/AN PN=N SX=C. SY=C. SXSQ=C. SXY=C. S YSQ=C. 917 DO 199 I =1,N SX=SX+X(l ) S Y =S Y +Y ( I ) SYSQ=SYSQ+Y (I )*Y(l ) SXY=SXY+X (I )*Y (l ) 199 SXSQ=SXSQ+X (l )*X (l ) PA=SXSQ-(SX*SX )/PN QA=SYSQ-(SY*SY)/PN BA=SXY-(SX*SY)/PN 22 SD=SQRTF ( (SRSQ/PN )- (AVE**2 ) ) S =BA / PA CORR=SQRTF((BA*BA)/(PA*QA)) YM=SY/PN XM=SX/PN ...... C=YM-S*XM RKLS =S RKLS=RKLS*VFAC 715 GO TO (128,29,29),I ORD 128 PCENT =CONC (N)/AO*1CC. GO TO 1C3 29 PCENT=CONC(N)/B0*1CC. 103 I F (SENSE SWITCH 2 )118,119 119 PRINT 27 , 27 FORMAT(7X13HC0NCENTRATI0N1OXAHTI ME 11X JAMBATE CONSTANT DO 17 I =1, N TIME(l ) =T I ME ( I )/6C. 517 PR I NT617, CONC ( I ), TI ME ( I ), RK ( I ) 17 TIME( I )=TI ME(I)*6C. 617 FORMAT(8XE11.A,8XF8.2 ,1CXE11.A ) PRINT Al PRINT 31,RKLS 144

PRINT 32,AVE ...... PRINT 33.CORR PRINT 34,SD PRINT 131,BO IF (A0)713,712,713 ...... 712 PRINT 133,BO GO TO 79 713 PRINT 133,AO 79 PRINT 75,PCENT 131 FORMAT(1CX34HAMIDE CONCENTRATION =F6.4,1HN ) 133 FORMAT (1CX34HCATALYST CONCENTRATION =F6.4,1HN ) 75 FORMAT(1CX34HPERCENTAGE OF REACTION FOLLOWED = F6.2 ) 34 FORMAT(1CX34HSTANDARD DEVIATION FROM MEAN = El 1.4 ) 33 FORMAT(1CX34HCORRELATION COEFFICIENT = E11.4 ) 32 FORMAT(1CX34HAVERAGE RATE CONSTANT = El 1.4 ) 31 FORMAT(1CX34HLEAST SQUARES RATE CONSTANT = El 1.4 ) PRINT 41 ...... PRINT 39 39 FORMAT(23X19H* * * ) PRINT 41 118 IF (SENSE SWITCH 1 )5CC,5C1 5CC PUNCH 81 5C1 GO TO 333 END

- PROGRAMME 2 - DI MENS I ON TIME (5C),RT (50), PCENT (50), RK (50), CRK (50) DIMENSION X (50), Y(50) 333 READ 200 PRINT 200 200 FORMAT(4CH PRINT 41 41 FORMAT(/) READ ICC,RO,RI,A,RIS, VFAC ICC FORMAT (5F1C.3 ) STDEV=C C=C RC=C RKSQ=C SUM=C I TT =0 SD=C S =0 C ORR =C DO 2 1=1,50 , % READ 100,TI ME(I),RT(I ) , PCENT(I ) IF (TI ME(l))1C,2C,2C 20 TIME (I ) =*TI ME ( I )*6C. 145

, RT (I )=RT(| )+RT (I )*PCENT(l ) /ICC. 194 RK(l )=1. / (A*TIME (l ) )* (l. /RO-1. /RT (l )) / ( l . /RT (l )-| /R| ) RK(l ) =RK( I )*VFAC ' SUM=SUM+RK(l ) X Cl ) = (l./RT(l )-1./RI )*TI ME (I ) Y(l )=1./RT(l ) 2 RKSQ=RKSQ + RK( I )**2 1C N=l-1 AN=N AVERK=SUM/AN STDEV=SQRTF (RKSQ/AN -AVERK**2) GO TO 49 73 SSD=STDEV RCE=RC SAVE=nAVERK C ORR E =C ORR ROE =4*0 RIE =RI ...... C VARIABLE INFINITY SUBROUTINE STDEV=1. SD=STDEV RI =R I S RINC=RIS/2C. I T =C 4CC RIST=RI R0ST=^0 RCST=RC SDST =SD IT=IT+1 RI^I+RINC DO 414 1=1,N X(l ) = (1. /RT (I )-1./RI )*TIME(l ) 414 Y(I)=1./RT(I) 49 PN=N SX=C. SY=C. SXSQ=C. SXY=C. SYSQ=C. 917 DO 199 1=1,N SX=SX+X (I ) S Y =S Y +Y (I ) SYSQ=SYSQ+Y ( I )*Y(l ) SXY=SXY+X(l ) *Y (I ) 199 SXSQ=SXSQ+X ( I )*X ( I ) PA=SXSQ-(SX*SX )/PN QA=S YSQ-(S Y*S Y )/PN BA=SXY- (SX*SY )/PN ...... S =BA / PA C ORR =SQRTF ( (BA *BA ) / (PA*QA) ) SD=SQRTF ( (QA- (BA*BA )/PA )/ (PN-2. )) YM=SY/PN XM=SX/PN C =YM-S *XM 146

RC=-S/A RC=*C*VFAC ITT=ITT+1 1F(ITT-1)238,73,238 238 R0=1. /C 1238 IF (SENSE SWITCH 3 )236,235 236 PRINT 131,IT.RC.RI,RO.SD.CORR 131 FORMAT(l2,3XEl1.if,3XE11.4,3XE11.A,3XE11.A.F1C.5) 235 IF (SD-SDST)4CC,60,60 ’ 60 IF(RINC-1. )8C,61,61 61 RINC=RINC/1C. Rl=RIST R0=R0ST RC=RCST SD=SDST GO TO HuvJiOO 80 Rl =RI ST RO=ROST RC=«CST SD=SDST PCT = (1. /RT (N)—1. /R0)/ (1. /Rl -1. /R0)*1CC. IF (SENSE SWITCH 2 )777,778 778 PRINT 29 29 FORMAT (lAXAHTIME8X1CHRESISTANCE8X13HRATE CONSTANT ) RKSQ=C. SUM=C. DO 90 I =1, N CRK(I ) =1. / (A*TI ME (I ))*(1./R0-1./RT(| ))/(1./RT(l )-1. /Rl ) CRK(I )=CRK(l )*VFAC SUM=SUM+CRK ( I ) RKSQ=RKSQ+CRK(l )**2 TIME(I ) =T I ME ( I )/6C. 590 PRINT lifC.TIME (I ),RT(l ),CRK(I ) 1 i+C FORMAT (lOXF9.2,7XF7.2,12XE11.if ) 90 TIME(I) =TI ME( I)*6C. AVERK=SUM/AN SD=SQRTF (RKSQ/AN-AVERK**2) PRINT if 1 PRINT 31,RC PRINT 32.AVERK PRINT 33,CORR PRINT 3b,SD PRINT 1131, A PRINT 21,RI PRINT 11,RO PRINT 75, PCT 79 FORMAT(11X3AHPERCENTAGE OF REACTION FOLLOWED = F6.2 ) 31 FORMAT (11X3AHLEAST SQUARES RATE CONSTANT = E l l . b ) 32 FORMAT(11X3AHAVERAGE RATE CONSTANT - E l l . b ) 33 FORMAT(11X3AHC0RRELATI ON COEFFICIENT = E l l . b ) 3k FORMAT(l1X3AHSTANDARD DEVIATION FROM MEAN = E l l . b ) 1131 F0RMAT(11X3AHC0NCENTRATI0N OF REACTANTS = F6.i , 1HN ) 147

21 FORMAT (11X3^HPREDICTED INFINITE RESISTANCE = F8.2 ) 11 FORMAT (11X34HPREDICTED ZERO RESISTANCE = F8.2 ) PRINT 41 PRINT 39 39 FORMAT(24X19H* * * ) PRINT 41 777 GOT0333 END * * * *

- PROGRAMME 3 - PRINT 42 42 FORMAT(/// ) 2C READ 20C PRINT 2CC 2CC FORMAT (4CH PRINT 4l 41 FORMAT(/) PRINT 123 123 FORMAT(l2X4HTEMP6X13HRATE CONSTANT ) PRINT 41 DIMENSION T (lCO ),RK (1CC),ERROR(1 CO) DIMENSION X (ICC),Y(ICC) J=C r=1.9871 82 DO 7 1=1, ICC READ.T (l ),RK(l ),ERROR(l ) I F (T (I ) )5,6, 6 6 X (I )=1./T(I ) PRINT 1C2, T ( I ),RK(l ) 1C2 FORMAT(1CX,F8.2,5X,E11.4 ) 7 Y(l )=1./2.3C3*LOGF(RK(l )/T(l )) 5 N=l -1 1C6 PN=N SX=C. S Y=C. SXSQ=C. SXY=C. S YSQ=C. 917 DO 199 1=1, N SX=SX+X(I ) SY=S Y+Y (l ) SYSQ=S YSQ+Y (l )*Y(l ) SXY=SXY+X (I )*Y (I ) 199 SXSQ=SXSQ+X (l )*X (l ) PA=SXSQ-(SX*SX )/PN QA=SYSQ-(SY*SY )/PN BA=SXY-(SX*SY)/PN 148

SD=SQRTF (ABSF ( (QA- (BA*BA )/ PA )/ (PN-2 . )) S=BA/PA CORR =SQRTF (ABSF ( (BA**2 ) / (PA*QA ))) YM=S Y/PN XM=SX/PN C=YM-S*XM SCORR=CORR SSD=SD SC =C IF (J —1>85,86,85 85 DO 79 I =1, N X (I )-1./T(l ) 79 Y(l )=LOGF(RK(l )) DH=-A.5753*S J — J +1 GO TO 1C6 86 E =-S*1.9871 ...... A=EXPF (C) READ ,TEMP ...... PK=A/(2.7182818**(E/(1.9872*TEMP)>) DS=-A7.212+DH/TEMP+1.9871*LOGF(PK/TEMP) DG=DH-TEMP*DS ARG=5. 6645*TEMP*(l C. 0**1 C) DELS=1.9871 *(C-LOGF (ARG )) PRINT 41 PRINT 3C,DH,DS,DG 30 FORMAT(7HDELH = FIC.2,5X7HDELS = FIC.2,5X7HDELG = F1C.2 ) PRINT41 81 PRINT 31,SCORR,SC,SSD 31 FORMAT(7HC0RR = F8.5,3 X12 HINTERCEPT = E1C.4,3X8HSTDEV = E1C.4 ) IF(SENSE SWITCH 1 )4CC,4C1 4C1 ERROR (l ) = (ERR0R(1 J+ERROR (2) )/2 . C ERROR(N) = (ERROR(N)+ERROR(N—1 ))/2.C TERM=SQRTF (ABSF ( (ERROR (N) /RK (N) )**2-(ERROR (1 )/RK (l ) )**2 )) EE=R*T(1 )*T (N)*TERM/ (T (N)-T (l )) TM = (T (l )+T(N))/2.C ES=EE/TM PRINT 2,EE,ES 2 FORMAT (/6HERRORS//7HDELTA H3XF1C.C,5X,7HDELTA S3XF1C.2 /) PRINT41 PRINT 776 776 FORMAT(26HARRHENIUS EQUATION RESULTS /) PRINT41 384 PRINT 4, E,TEMP,DELS,A , 4 FORMAT (4H E= E15.7/6H DELS ( F7.1.4H) = F8.3/4H A = E15.7///) 4CC PRINT 42 GO TO 2C END * * * * 149 150

APPENDIX 2.

STATISTICAL TESTS EMPLOYED

All experimental measurements are subject to

experimental errors and in many cases the conditions pertaining during an experiment are such that individual results are subject to chance variations comparable in

size to the effect under consideration. As the

complexity of* the data increases it becomes increasingly

difficult to draw reliable conclusions without the aid of*

some statistical treatment.

The fallowing parameters were used to assess the

significance of the correlations obtained in the present

work.

1) Standard Deviation The most important measure of dispersion or scatter

in an array X is the standard deviation which is defined

as

where n is the number of observations in the array

and X is the arithmetic mean of the array. 151 Generally speaking a unimodal distribution has

a) 66$ of* the array within one standard deviation

of the mean

b) 95$ of the array within two standard deviations of the mean, and

c) less than 1$ of the array more than three

standard deviations from the mean - i.e„ good correlations are characterised by minimal standard deviations•

The standard deviation of an array is related to the variance of an array by the expression

s

Variance is an important statistical parameter used in determining the significance levels of correlations.

2) Correlation Co-efficient An excellent estimate of the degree of association between two variables X and Y, is given by the correlation co—efficient which is defined as

r Co-Vqrjqnce of X and Y

or as

s(x-s y - y ) r It is easily shown that correlation co-efficients are restricted such that -1 ^ r ^ 1 . A high absolute value of r indicates a close relationship and a small value a less definite relationship#

Correlation co-efficients and standard deviations have been used extensively throughout the literature to assess the worth of correlations and accepted norms have 27 arisen# However, recent workers have recognised that

it is not justifiable to compare correlation co-efficient which have differing degrees of freedom. Statistical

tests have been developed to assess the significance of

correlation co—efficients, or any improvement in

correlation co-efficient produced by omitting one or two

data pairs fromthe correlation or by adding extra

variables to the relationship being tested.

3 ) Variance Ratio Test (Snedecor 1s F—Test) One of the most commonly used methods to determine whether two estimates differ significantly, i.e. by more

than can be reasonably explained by errors in the

estimates, is the Variance Ratio F-Test. The F-ratio

is defined as

F greater variance estimate_ lesser variance estimate 153

If th.e Null Hypothesis is true, viz» that the improvement in correlation is insignificant, then F is approximately unity. If however, F is considerably greater than unity, then the number of data pairs, i.e. the number of degrees of freedom, must also be considered.

The number of degrees of freedom for a sample of n items correlated by a relationship containing k independent variables is [n-(k+l)J . The F ratio and the number of degrees of freedom can then be used, inconjunction with

Snedecor’s F-Tables, to predict a significance level for the improved correlation, e.g. if the F-test indicates that the improvement in correlation is significant at the

0.1 tfo level then the odds that the improvement arose purely by chance are 1000/1.

Student*s t-Test

For single randomised samples consisting of less than

thirty measurements the confidence criterion most commonly used is the Student* s t-test. The Student t, defined as

+ IX—x / ■ ] n - Y - r J/v-z t = 5 " J / ->* ■

where s is the standard deviation N and n are the number of observations X is the mean of the proposed hypothetical population, and x is the mean of the sample, r is the correlation co-efficient 154 is used to assess the unrealiability, or lack of precision, of a correlation in small samples.

As in the F-Variance Ratio test the number of degrees of freedom and the t statistic are used in conjunction with standard tables of t to predict a confidence or significance level for the correlation.

In the present study the above mentioned parameters were used to determine the significance of any correlation, or improvement in correlation co-efficient, brought about by either

a) removal of a deviant point s from the correlation, or

b) including an extra parameter in the correlation. HYDROLYSIS OF AMIDES

A KINETIC STUDY OF SUBSTITUENT EFFECTS ON THE ACIDIC AND BASIC HYDROLYSIS OF AMIDES

by G. L. JACKSON VOLUME 2 (OF 2) INTRODUCTION

In order to maintain continuity in Volume 1, a complete listing of the experimental results obtained in the present study was deferred. This listing makes up Volume 2 and, unless otherwise stated in the text, the following system of units has been employed in the listing:-

rate constant 1.mole

time mins •

resistance ohms

concentration moles 1

c ondu c t ance ohms **

In order to avoid "round-off" errors the computer was programmed to output the results to more than the correct number of significant figures. Undue emphasis should not therefore be placed upon the computer output, but upon the values and their error analyses as they appear in the summary tables on pages 1 Qfld 43 CONTENTS

PAGE

A) ACIDIC HYDROLYSIS OF AMIDES

1. SUMMARY OF ACIDIC HYDROLYSIS DATA USED 1

2. RESULTS FROM THE PRESENT STUDY 3

ISO-VALERAMIDE 3 PHENYLACETAMIDE 6 CYCLOHEXYLACETAMIDE 11 METHOXYACETAMIDE 16 LSa-BUTYRAMIDE 19 ^-METHYLBUTYRAMIDE 22 CYCLOPENTANECARBOXAMIDE 25 CYCLOHEXANECARBOXAMIDE 28 DIETHYLACETAMIDE 32 TRIMETHYLACETAMIDE 35 2 .2-DIMETHYLBUTYRAMIDE 38

3. RESULTS FROM AUTHOR’ S HONOURS THESIS 4l

4. RESULTS FROM PREVIOUS V/ORKERS 42

B) BASIC HYDROLYSIS OF AMIDES

1. SUMMARY OF BASIC HYDROLYSIS DATA USED 43

2. RESULTS FROM PRESENT STUDY

ACETAMIDE 44 PROP IONAMIDE 48 BUTYRAMIDE 51 VALERAMIDE 54 ISO-VALERAMIDE 57 PHENYLACETAMIDE 60 CYCLOHEXYLACETAMIDE 63 METHOXYACETAMIDE 66 CYCLOHEXANECARBOXAMIDE 69 CYCLOPENTANECARBOXAMIDE 72 -METHYLBUTYRAMI DE 75 ISO-BUTYRAMIDE 78 TRIMETHYLACETAMIDE 8l 1

ACIDIC HYDROLYSIS OF ALIPHATIC AMIDES

AMIDE TEMPERATURE RATE CONSTANT x

PROPANAMIDE 65. C 5.64 (iC. 19) 75.0 12.C ( 0.30) 85.0 26.9 ( 0.90) BUTANAMIDE 65.0 2.56 ( 0.10) 75.0 5.99 ( 0.17) 85.0 13.0 ( 0.30)

VALERAMIDE 55.0 1.08 ( 0.03) 65.0 2.70 ( 0.06) 75.0 5.93 ( 0.05) ISO-VALERAMIDE 65.0 0.545 ( 0.002) 7 5 .C 1.29 ( 0.01) 85.0 2.96 ( 0.03)

PHENYLACETAMIDE 75.0 5.19 ( 0.28) 85.0 12.9 ( 0.30) 95.0 22.5 ( 0 . 3 0 )

CYCLOHEXYLACETAMIDE 75.0 1.24 ( 0.05) 85.0 2.98 ( 0.03) 95.0 6.75 ( 0.08)

METHOXYACETAMIDE 55.0 1.59 ( 0.04) 65.0 3.79 ( 0.09) 75.0 8.98 ( 0.10)

CHLOROACETAMIDE 55.0 2.19 ( c.ic) 65.0 5.52 ( 0. 11) 75.0 12.1 ( 0.60)

BROMOACETAMIDE 45.0 0.798( 0.03) 55.0 2.13 ( 0.11) 65.0 4.79 ( 0.14)

3 .3-D 1METHYLBUTYRAMIDE 75.0 0.193( C.CC5) 85.0 0.465 ( C.CC6) 95.0 1.03 ( 0.03)

ISO-BUTYRAMIDE 75.0 6.06 ( 0.01 ) 85.0 13.7 ( 0 . 0 1 ) 95.0 29.6 ( 0.03)

»¿-METHYLBUTYRAMIDE 75.0 1.51 ( 0.05) 85.0 3.86 ( 0.10) 95.0 8.50 ( C.0 9 ) 2

ACIDIC HYDROLYSIS OF ALIPHATIC AMIDES (CONT. )

AMIDE TEMPERATURE RATE CONSTANT X 1

CYCLOPENTANECARBOXAMIl DE 75.0 9.06 (- ;0 . 15 ) 85.0 17.5 ( 0.01 ) 95.0 29.6 ( 0.07)

CYCLOHEXANECARBOXAMI DE 75.0 3.96 ( 0.06) 85.0 8.90 ( 0.10) 95.0 20.5 ( 0.07)

rv n n i DIETHYLACETAMIDE 75.0 0 .1 7 6 ( \J 0 KJ KJ I 85.0 0.667 ( 0.C6) 95.0 1.06 ( 0.03 )

TRIMETHYLACETAMIDE 65.0 0.935 ( 0.09) 75.0 2.26 ( 0.02) 85.0 5.16 ( 0.03)

ACETAMIDE 65.0 6 .3 0 ( 0.01 ) 7 C r» / J . ^ 10.3 ( 0.06) 8f>. G 21.9 ( 0.06)

2 .2-DIMETHYLBUTYRAMI DE 75. C 0.058 ( 0.25) n o n r\ ( 85. C KJ , t U U V 0.59) 95. C 0.626 ( 0.18)

NUMRERS IN PARENTHESES ARE THE STANDARD ERRORS OF MEASUREMENT OF K2. 3

ISOVALERAMIDE AT 65 DEGS. RUN 1

CONCENTRATION TIME RATE CONSTANT 0.2958E-01 786.00 0 . 5466E-0 4 0.2943E-01 786.00 0.5429E-04 0.4599E-01 1490.50 0.5425E-04 0.4599E-01 1490.50 0.5425E-04 0.5246E-01 1835.25 0.5480E-04 0.5246E-01 1835.25 0 . 5480E-04 0.5821E—01 2217.50 0.5474E-04 0.5823E-01 2217.50 0.5477E-04 0.6654E-01 2921.25 0.5439E-04 0.6657E-01 2921.25 0.5445E-04 O.6982E-OI 3221.25 0.5490E-04 0.6967E-01 3221.25 0.5463E-04 0.7274E-01 3578.50 0. 5444E-04 0.7264E-01 3578.50 0.5426E-04

LEAST SQUARES RATE CONSTANT 0.5450E-04 AVERAGE RATE CONSTANT 0.5455E-04 CORRELATION COEFFICIENT 0.9999 STANDARD DEVIATION FROM MEAN 0 . 2289E-06 AMIDE CONCENTRATION .1 225N CATALYST CONCENTRATION .1253N PERCENTAGE OF REACTION FOLLOWED 57-98

ISOVALERAMIDE AT 65 DEGS. RUN 2

CONCENTRATION T IME RATE CONSTANT 0.1850E-01 410.00 0.5454E-04 0 . 1842E-01 410.00 0.5426E-04 0.4833E-01 1465.50 0.5476E-04 0 .4828E-01 1465.50 0.5468E-04 0.5463E-01 1810.00 0.5441E-04 0.5451E-01 1810.00 0.5421E-04 0.6090E-01 2193.25 0.5474E-04 0.6089E-01 2193.25 0.547 IE-04 0.6962E-01 2896.75 0.5444E-04 0.6975E-01 2896.75 0.5466E-04 0.7283E-01 3195.75 0.5460E-04 0.7292E-01 3195.75 0.5477E-04 0.7597E-01 3568.00 0.5409E-04 0.7626E-01 3568.00 0.5460E-04

LEAST SQUARES RATE CONSTANT = 0.5442E-04 AVERAGE RATE CONSTANT = 0.5453E-04 CORRELATION COEFFICIENT = 0.9999 STANDARD DEVIATION FROM MEAN = 0.2)28E-06 AMIDE CONCENTRATION = .13 ION CATALYST CONCENTRATION = .1 253N PERCENTAGE OF REACTION FOLLOWED = 58.21

k k k 4

ISOVALERAMI DE AT 75 DECS. RUN 2

CONCENTRAT ION T IME RATE CONSTANT 0.3204E-01 358.75 0.1297E-03 0.3178E-01 358.75 0.1283E-03 0.41 54E-01 528.25 0.1271E-03 0.4164E-01 528.25 0.1276E-03 0.5049E-01 721.75 0 .1 266E-03 0.5054E-01 721.75 0 . 1267E-0 3 0.5857E-01 916.75 0 . 1295E-0 3 0.5843E-01 916.75 0 .1 289E-0 3 0.6337E-01 1072.25 0.1290E-03 O.6 3 I9E-01 1072.75 0.1283E-03 0.6784E-01 1244.75 0 .1 282E-03 0.6764E-01 1244.75 0.1274E-03 0.7055E-01 1355.50 0.1285E-03 0.7041E-01 1355.50 0 . 1279E-0 3

LEAST SQUARES RATE CONSTANT 0 .1 284E-03 AVERAGE RATE CONSTANT 0.128 IE-03 CORRELATION COEFFICIENT 0.9999 STANDARD DEVIATION FROM MEAN 0.9418E-06 AMIDE CONCENTRATION . 1 247N CATALYST CONCENTRATION .1 253N PERCENTAGE OF REACTION FOLLOWED 56.46

ISOVALERAMI DE AT 75 DEGS. RUN 1

CONCENTRATION TIME RATE CONSTANT O.3 1 7 IE -0 1 360.75 0.1267E-03 0.317 2E-01 360.75 0 .1 268E-03 0.4310E-01 544.00 0 . 1300E-03 0.4294E-01 544.00 0 .1 293E-03 0.5108E-01 720.00 0 .1 288E-03 0 .5 1 14E-01 720.00 0.1291E-03 0.5955E-01 932.00 0.1308E-03 0.5959E-01 932.00 0.1310E-03 0.6428E-01 1084.75 0.1307E-03 0.6433E-01 1084.75 0 . 1309E-0 3 0.6835E-01 1251.75 0 . 1289E-0 3 0.6810E-01 1251.75 0 .1 279E-03 0.7089E-01 1349.50 0 .1 298E-0 3 0 . 7 103E-01 1349.50 0 . 1304E-03

LEAST SQUARES RATE CONSTANT = 0.1304E-03 AVERAGE RATE CONSTANT = 0.1294E-03 CORRELATION COEFFICIENT = 0.9997 STANDARD DEVIATION FROM MEAN = 0.1377 E—0 5 AMIDE CONCENTRATION = . 1 263N CATALYST CONCENTRATION = .1253N PERCENTAGE OF REACTION FOLLOWED = 56.24

■:< 5

ISOVALERAMIDE AT 85 DEGS. RUN 1

CONCENTRATION TIME RATE CONSTANT 0.1653E-01 74.00 0 .28 4 IE-03 0 . 1660E-01 74.00 0.2855E-03 0.4757E-01 29O.5O 0 . 2920E-03 0.4751E-01 290.50 0.2914E-03 0.553 IE-01 377.00 0.2907E-03 0.5492E-01 377.00 0.2870E-03 0.6060E-01 447.75 0.2903E-03 0.6040E-01 447.75 0.2885E-03 0.6446E-01 515.50 0.2854E-03 0.6461E-01 515.50 0.2868E-03 0.6775E-01 570.75 0.2866E-03 0.6793E-01 570.75 0 . 2883E-0 3 LEAST SQUARES RATE CONSTANT = 0.2869E-03 AVERAGE RATE CONSTANT = 0 . 2880E-03 CORRELATION COEFFICIENT = 0.9999 STANDARD DEVIATION FROM MEAN = 0.2476E-05 AMIDE CONCENTRATION = .1253N CATALYST CONCENTRATION = . 1 24 2N PERCENTAGE OF REACTION FOLLOWED = 54.22

ISOVALERAMIDE AT 85 DEGS. RUN 2

CONCENTRAT ION TIME RATE CONSTANT 0.2967E-01 151.75 0.2829E-03 0.2978E-01 151.75 0.2844E-03 0.4834E-01 301.00 0.2892E-03 0.4805E-01 301.00 0.2865E-03 0.5432E-01 374.00 0.2838E-03 0.5466E-01 374.00 0.2870E-03 0.6059E-01 449.00 0.2894E-03 0.6063E-01 449.00 0.2898E-03 0.6513E-01 513.75 0.2926E-03 0.6488E-01 513.75 0.2903E-03 0.6777E-01 565.25 0.2895E-03 0.6772E-01 565.25 O.289IE-0 3 LEAST SQUARES RATE CONSTANT 0.2929E-03 AVERAGE RATE CONSTANT 0.2879E-03 CORRELATION COEFFICIENT 0.9998 STANDARD DEVIATION FROM MEAN 0.2847E-05 AMIDE CONCENTRATION .1 253N CATALYST CONCENTRATION . 1 24 2N PERCENTAGE OF REACTION FOLLOWED = 54.04 6

PHENYLACETAMIDE AT 75 DEGS. RUN 1

TIME RESISTANCE RATE CONSTANT 30.00 65.13 0 .4 1 27E-O3 60.00 66'. 66 0 .5648E-O3 90.00 67.54 O.516 7E-O3 120.00 68.59 O.5 I 6OE-O3 150.00 69.65 0 .5 1 92E-03 180.00 70.96 O.545OE-O3 210.00 71.57 0 .5 1 22E-03 240.00 72.43 O.5056E-O3 270.00 73'. 47 0 .5 1 22E-03 300.00 74.44 0 .51 47E-O3 330.00 75.38 0 .5 1 5SE-O3 360.00 76.61 O.5323E-O3 390.00 77.15 0.5162E-03 420.00 78.16 0 . 5223E-0 3 450.00 78.68 O.5O9IE-O3 480.00 79.60 0; 512SE-03 510.00 80.68 O.523OE-O3

LEAST SQUARES RATE CONSTANT = o ; 5178E-0 3 AVERAGE RATE CONSTANT = 0.5147E-03 CORRELATION COEFFICIENT = 0.9991 STANDARD DEVIATION FROM MEAN = O .2913E-0 4 CONCENTRAT ION OF REACTANTS = .0319N PREDICTED INF IMITE RESISTANCE = 166.18 PREDICTED ZERO RESISTANCE = 64.23 PERCENTAGE OF REACTION FOLLOWED = 33.23 7

PHENYLACETAMIDE AT 75 DECS. RUN 2

TIME RESISTANCE RATE CONSTANT 60.00 69.62 0.6345E-03 100.00 71.07 O.6OO9E-O3 140.00 71-93 0.5243E-03 180.00 72.93 O.4959E-O3 220.00 73.89 O.4769E-O3 260.00 75.15 0.4846E-03 300.00 76.58 O.502IE-O3 340.00 78 .0 0 O.518OE-O3 438.25 80.92 O.528OE-O3 460.00 81.41 0.5240E-03 507.00 82.37 O.5138E-O3 540.00 83.29 O.5178E-O3 580.00 84.25 O.5 17 3 E-O3 620.00 85.26 O.5193E-O3 660.00 86.52 O.5 3 IOE-O3 700.00 87.17 0.5224E-03 740.00 88.40 O.5336E-O3 780;00 88 ;8 2 0 . 5195E-0 3 820.00 89.78 O-.5232E-O3 860;00 90.95 0.5342E-03 1600.00 102.69 O.52I 8E-O3 1640;00 103.43 O.5269E-O3 1680.00 103.79 O.523IE-O3 1720.00 104.21 O.5208E-O3 1760.00 104.57 O.5176E-O3 1800.00 104.95 0 . 5149E-03 1840.00 105.47 O.516OE-O3 1880.00 106.42 0.5274E-03 1932.00 106.52 0.5154E-03 1972.00 107.00 0 . 5162E-03 2066.75 108.49 O.5268E-O3

LEAST SQUARES RATE CONSTANT = O .52IOE-O3 AVERAGE RATE CONSTANT = 0.5241E-03 CORRELATION COEFFICIENT = 0.9993 STANDARD DEVI,AT ION FROM MEAN = O .2786E-0 4 CONCENTRATION OF REACTANTS = .0319N PREDICTED INF IN ITE RESISTANCE = 156.00 PREDICTED ZERO RESISTANCE = 66.98 PERCENTAGE OF REACTION FOLLOWED = 67.05 8 PHENYLACETAMIDE AT 85 DECS. RUN 1

TIME RESISTANCE RATE CONSTANT 100:00 69.17 0 . 1288E-02 140.00 71.64 O.I278E-O2 180.00 74.00 0 .1 280E-02 260.00 78.47 0 . 1306E-02 300.00 80.20 0 . 1289E-0 2 340.00 8 2.00 O.I29OE-O2 380.00 83.75 0 . 1296E-02 420.00 85.57 0 .1 3 16E-02 460.00 86.65 0.1283E-02 500.00 88.40 O.I3 IOE-O2 540.00 89.36 0.1 28 2E-02 580.00 90.50 0.1274E-02 620.00 91.82 0 . 1283E-02 660.00 93.00 0 . 1287E-02 700.00 94.14 0 .1 2S2E-02 740.00 95.24 O.I298E-O2 LEAST SQUARES RATE CONSTANT = 0.1291E-02 AVERAGE RATE 'CONSTANT = O-.I29IE-O2 CORRELATION COEFFICIENT = 0.9994 STANDARD DEVIATION FROM MEAN = 0.1135E-04 CONCENTRAT ION OF REACTANTS = .O319N PREDICTED INF INITE RESISTANCE = 136:50 PREDICTED ZERO RESISTANCE = 61.87 PERCENTAGE OF REACTION FOLLOWED = 64.08

PHENYLACETAMIDE AT 85 DECS. RUN 2

TIME RESISTANCE RATE CONSTANT 60.00 6 7:54 0.1215E-02 100.00 70.60 0.132SE-02 140.00 72.34 0 .1 215E-02 180:00 7 5.34 0.1328E-O2 220.00 77.46 O.I33OE-O2 26O.OO 80.00 0.1394E-02 300.00 80.68 0.1275E-02 380:00 85.26 0 .1 400E-02 420.00 8 5:48 0 * 1206E-O2 460.00 06.70 0 . 1273E-02 500.00 88.40 0.1306E-02 540.00 89.36 0.1265E-02 580.00 90.45 0 . 12G0E-02 620.00 91.63 0 .1 288E-02 660.00 93.00 0 . 1314E-02 740.00 95.14 0.1332E-02

LEAST SQUARES RATE CONSTANT - O .I306E-O2 AVERAGE RATE CONSTANT - 0.13 03 E—0 2 CORRELAT I ON COEFF1C1 ENT - 0.9960 STANDARD DEVI AT ION FROM MEAN = 0 .A963E-0A CONCENTRATION OF REACTANTS = .0319N PREDICTED INF INITE RESISTANCE = 131.00 PREDICTED ZERO RESISTANCE = 6 3 .3O PERCENTAGE OF REACTION FOLLOWED = 6k . 68 9

PHENYLACETAMIDE AT 95 DEGS. RUN 1

TIME RESISTANCE RATE CONSTANT 61.00 66.46 0.2261E-02 81.00 68.71 0.2306E-02 101.00 70.75 0.2318E-02 121.00 72.29 0.2248E-02 141.00 74.25 0.2295E-02 161.00 76.15 0.2342E-02 181.00 77.69 0.2337E-02 201.00 78.84 0.2286E-02 221.00 80.12 0.2270E-02 241.00 81.55 0.2289E-02 261.00 8 2.67 0.2271E-02 281.00 84.04 0.2299E-02 301.00 85.09 0 ; 2288E-02 321.00 86.39 0.2321E-02 341.00 87.17 o . 2289E-02 361;00 88.35 0.2316E-02 381.00 88.82 0.2256E-02 401.00 90.18 0.2317E-02

LEAST SQUARES RATE CONSTANT = 0.2295E-02 AVERAGE RATE CONSTANT = 0.2295E-02 CORRELATI ON COEFFICIENT = O .999I STANDARD DEVI,AT I ON FROM MEAN = 0.2637E-04 CONCENTRATION OF REACTANTS = .0319N PREDICTED INF IN ITE RESISTANCE = 130.00 PREDICTED ZERO RESISTANCE = 59.10 PERCENTAGE OF REACTION FOLLOWED = 63.19 * 10

PHENYLACETAMIDE AT 95 DEGS. RUN 3

TIME RESISTANCE RATE CONSTANT 60-.00 67.17 0.23A6E-02 80.00 68.66 0.2158E-02 100.00 71.00 0.2261E-02 120.00 7 2 .6A 0.2217E-02 1A0.00 7 A. 66 0.2276E-02 160.00 76.53 0.2317E-02 180.00 78.16 0.23 28E-02 200.00 79.20 0.2258E-02 220.00 80.52 0.22A9E-02 2A0.00 81.96 0.2269E-02 260.00 83.12 0.2258E-02 280.00 8A.38 0.2269E-02 300.00 85.A3 0.2258E-02 320.00 86.52 0.2262E-02 3AO.00 88.00 0.2325E-02 360.00 88.38 0.22AAE-02 380.00 89. A5 0 . 2263E-0 2 AO0.00 90:1 A 0.2237E-02 A20.00 91 - A1 0 : 2292E-02 AA0.00 91.95 0.2257E-02 LEAST SQUARES RATE CONSTANT = 0.2267E-02 AVERAGE RATE iCONSTANT = 0.2267E-02 CORRELATION COEFFICIENT = 0:9987 STANDARD DEVIATION FROM MEAN = O.A06Ì+E-OA CONCENTRAT ION OF REACTANTS = .0319N PREDICTED INF IN ITE RESISTANCE = 130.50 PREDICTED ZERO RESISTANCE = 59.6A PERCENTAGE OF REACTION FOLLOWED = 6A.72 11

CYCLOHEXYLACETAMIDE AT 75 DECS. RUN 1

TIME RESISTANCE RATE CONSTANT 986.75 86.60 0.1203E-03 1046.75 87.13 0 .1 200E-03 1106.75 87.91 0.1229E-03 1166.75 88.40 0 .1 222E-03 1226.75 88.64 0 .1 1 90E-03 1 286.75 89.13 0 .1 186E-03 1346.75 89.71 0.1192E-03 1406.75 90.00 0.1170 E—03 1466.75 90.59 0.1178E-03 2433.50 98.51 0 .1 202E-03 2493.50 98.95 0 .1 202E-03 2553.50 99.45 0.1206E-03 2613.50 99.65 0.1191E-03 2673.50 100.20 0 .1 1 98E-03 2733.50 100.65 0 .1 200E-03 2793.50 101.40 0 .1 220E-03 2853.50 101.81 0.1219E-03 2913.50 101.80 0.1193E-03 3864.00 108.00 0.1195E-03 3924.00 108;40 0.1197E-03 3984.00 108.73 0.1196E-03 4044.00 105.00 0.1191E-03 4289.00 110.66 0 .1 202E-03

LEAST SQUARES RATE CONSTANT = 0.1199E-03 AVERAGE RATE CONSTANT = 0;1199E-03 CORRELATION COEFFICIENT = 0.9995 STANDARD DEVIATION FROM MEAN = 0.13^6E-05 CONCENTRAT ION OF REACTANTS = .0319N PREDICTED IN F IN ITE RESISTANCE = 204.00 PREDICTED ZERO RESISTANCE = 76.80 PERCENTAGE OF REACTION FOLLOWED = 49.08 12

CYCLOHEXYLACETAMIDE AT 75 DECS. RUN 2B

T IME RESISTANCE RATE CONSTANT 244.00 64.60 0.1426E-03 325.00 64.80 0 .1 156E-03 372.50 65.30 0 .1 1 9SE-03 446.25 65.90 0 .1 1 92E-03 748.25 68.60 0.1249E-03 1256.00 72.00 0.118 2E-03 1408.00 73.40 0.1226E-03 1494.50 74.00 0 .1 226E-03 1603.50 74.50 0 . 1199E-0 3 1693.50 75.20 0.121 IE-0 3 1883.00 76.50 0.1220E-03 2053.00 78.40 0 . 1303E-0 3 2170.00 79.20 0 . 130SE-0 3 2904.00 82.80 0 .1 252E-03 3167.25 83.70 0 . 1216E-03 3310.50 84.60 0.1230E-03 4297.50 88.90 0.1216E-03

LEAST SQUARES RATE CONSTANT = 0 .1234E-03 AVERAGE RATE CONSTANT = 0 .1236E-03 CORRELATION COEFFICIENT = 0.9980 STANDARD DEVI AT ION FROM MEAN = 0.6042E-05 CONCENTRATION OF REACTANTS = .0370N PREDICTED INF IN ITE RESISTANCE = 144.00 PREDICTED ZERO RESISTANCE = 62.02 PERCENTAGE OF REACTION FOLLOWED = 53.11 13

CYCLOHEXYLACETAMIDE AT 85 DEGS. RUN 1

TIME RESISTANCE RATE CONSTANT 602;25 78.70 0.3222E-03 662.25 79.28 0.3098E-03 722.00 80; 68 0.3224E-03 788.50 81.43 0 .3145E-03 861.50 82.53 0.3147E-03 953-75 83.92 0 .3 1 56E-03 1015.00 84.62 0 .3 1 20E-03 1075.00 85.64 0 .3162E-03 1140.00 86.57 O.3173 E—03 1181.75 87.00 0.3149E-03 2121.00 97.95 0.3244E-03 2181.50 98.44 0.3232E-03 2249.25 98.55 0 .3152E-03 2313.75 99.00 0.3133E-03 2429.00 100.50 0.321 IE-03 2519.00 101.25 0.3211E-03 2590.00 101.56 0.3169E-03 2748.00 102.51 0 .3 1 26E-03 2820.00 103.06 0 .3 1 28E-03 3600.00 108.40 0.3141E—03

LEAST SQUARES RATE CONSTANT = 0.3168E-03 AVERAGE RATE CONSTANT = O.3 I 6 7E-O3 CORRELATION COEFFICIENT = 0.9989 STANDARD DEVI AT ION FROM MEAN = 0.4117 E—05 CONCENTRATION OF REACTANTS = .0317N PREDICTED INF INITE RESISTANCE = 154.00 PREDICTED ZERO RESISTANCE = 66.96 PERCENTAGE OF REACTION FOLLOWED = 67.64 14

CYCLOHEXYLACETAMIDE AT 85 DEGS. RUN 3

TIME RESISTANCE RATE CONSTANT 719.00 79.60 0.2848E-03 784.75 81.36 O.3OO8E-O3 841.00 81.80 O.29OOE-O3 890.50 8 2.50 0.2885E-03 968.50 83.87 0.2919E-03 1028.00 85.00 0.2962E-03 1106.50 86.00 0.2932E-03 1157.50 86.87 0.2955E-03 1236.00 88.00 0 . 2957E-03 2161.00 98.51 0 . 2859E-03 2228.50 99 • 45 0.2889E-03 2280.00 100.05 0.2S99E-03 2360.50 101.51 0.2980E-03 2412.50 101.85 0.2958E-03 2470.75 102;38 0.2S54E-03 2522.25 102.85 0.2950E-03 2580.50 103;38 0.2948E-03 2656.25 104.00 0.2938E-03 2748.75 104.48 0-.2895E-03 28 97'.00 106.21 0.2947E-03 3 6 0 7 .OO 111.50 0.2911E-03

LEAST SQUARES RATE CONSTANT = 0;2929E-03 AVERAGE RATE CONSTANT = 0;2928E-03 CORRELATION COEFFICIENT = 0-.9988 STANDARD DEVIATION FROM MEAN = 0.3932E-05 CONCENTRAT ION OF REACTANTS = .0317N PREDICTED INF IN ITE RESISTANCE = 172.50 PREDICTED ZERO RESISTANCE — 66.12 PERCENTAGE OF REACTION FOLLOWED = 66.00 15 CYCLOHEXYLACETAMIDE AT 95 DECS. RUN 1

TIME RESISTANCE RATE CONSTANT 62.25 58.52 0.6779E-03 129.00 61.03 0.6939E-03 183.50 62.43 0.6417E-03 280.00 65.33 0.6462E-03 332.25 66.97 0.6610E-03 415.00 69.20 0.6665E-03 489.00 71.07 0 .6 7 17E-03 553.00 7 2.66 0.6797E-03 610.00 73.77 0.6736E-03 664.50 74.90 0.6745E-03 7 28.50 76.00 0.6679E-03 792.50 77.20 0.6697E-03 842.00 78 .0 0 0.6670E-03 1580.00 87.60 0.6675E-03 1698.50 88.60 0.6617E-03

LEAST SQUARES RATE CONSTANT = 0.6677E-03 AVERAGE RATE CONSTANT = 0.6680E-03 CORRELATION COEFFICIENT = 0.9996 STANDARD DEVIATION FROM MEAN = 0.1225E-04 CONCENTRATION OF REACTANTS = .0349N PREDICTED INFI NITE RESISTANCE = 119.00 PREDICTED ZERO1 RESISTANCE = 56.09 PERCENTAGE OF REACTION FOLLOWED = 69.40

CYCLOHEXYLACETAMIDE AT 95; DEGS. RUN 2

TIME RESISTANCE RATE CONSTANT 61.00 66:30 0.6290E-03 118.50 68.6 2 0.6441E-03 188.50 71.64 0.6847E-03 253.00 73.63 0.6568E-03 304.50 75.96 0.6970E-03 361.50 77.61 0.6822E-03 428.00 79.32 0.6634E-03 481.00 81.36 0.6886E-03 543.50 82.63 0.6657E-03 697.25 86.57 0.6675E-03 767.00 88.48 0.6790E-03 831.00 89.46 0.6622E-03 872.50 90.91 0.6831E-03 1577.50 102.20 0.6659E-03

LEAST SQUARES RATE CONSTANT = 0.6721E-03 AVERAGE RATE CONSTANT = 0.6692E-03 CORRELATION COEFFICIENT = 0.9992 STANDARD DEVIATION FROM MEAN = 0.1763E-04 CONCENTRATION OF REACTANTS = .0317N PREDICTED INFI MITE RESISTANCE = 148.50 PREDICTED ZERO RESISTANCE = 63.81 PERCENTAGE OF REACTION FOLLOWED = 65.87 * 16

METHOXYACETAMIDE AT 55 DEGS. RUN 1

CONCENTRAT ION T IME RATE CONSTANT 0.3173 E—01 507.25 0 .1 A65E-03 0 .3 1 56E-01 507.25 0.14 53 E—03 0 .4 1 27E-01 723.00 0 .1 546E-03 0.4119E-01 723.00 0 .1541E-0 3 0.4623E-01 892.00 0 .1 528E-03 0.4618E-01 892.00 0 .1525E-03 0 . 5242E-01 1060.25 0.1639E-03 0.4946E-01 1060.25 0.1460E-03 0.5459E-01 1206.25 0.1569E-03 0.5440E-01 1206.25 0.1558E-03 0 . 5933E-01 1427 - 50 0.1601E-03 0.5943E-01 1427.50 0.1607E-03

LEAST SQUARES RATE CONSTANT = 0.1664E-03 AVERAGE RATE CONSTANT = 0.154 IE-03 CORRELATION COEFFICIENT = 0.9966 STANDARD DEVI AT ION FROM MEAN = 0.5717E-05 AMIDE CONCENTRATION = . 0995N CATALYST CONCENTRATION = •1050N PERCENTAGE OF REACTION FOLLOWED = 56.60 JL.7\ ^ /\ /s

METHOXYACETAMIDE AT 55 DEGS. RUN 2

CONCENTRAT ION TIME RATE CONSTANT 0.3230E-01 501.75 0 . 1503E-03 0.3320E-01 50 1.75 0.1565E-03 0 . 4173E-01 715.75 0 . 1572E-03 0 .4169E-OI 715.75 0.1569E-03 0.4593E-01 884.50 0.1504E-03 0.4721E-01 884.50 0.1581E-03 0.5083E-01 1051.75 0 . 1532E-03 0.5106E-01 1051.75 0.1546E-03 0.547 3 E—01 1197.75 0.1566E-03 0 . 5A6 7E-01 1197.75 0 . 1563E-0 3 0.5836E-01 1418.75 0 .1 526E-03 0 . 5822E-01 1418.75 0 .1 518E-03

LEAST SQUARES RATE CONSTANT = 0 . 1523E-03 AVERAGE RATE CONSTANT = 0 .1 545E-03 CORRELATION COEFFICIENT =; 0.9987 STANDARD DEVIATION FROM MEAN = 0 . 2666E-05 AMIDE CONCENTRATION = . 1004N CATALYST CONCENTRATION = .1050N PERCENTAGE OF REACTION FOLLOWED = 55.45

A 17

METHOXYACETAMIDE AT 65 DEGS. RUN 1

CONCENTRATION T IME RATE CONSTANT 0.3524E-01 183.25 0.37 57E-03 0.3559E-01 183.25 0.3813E-03 0.4688E-01 27 4.75 0.3935E-03 0.4666E-01 274.75 0.3903E-03 0.5407E-01 350.50 0.4005E-03 0.5348E-01 350.50 0.3921E-03 0.5821E-01 438.75 0.3713 E—03 0.6451E-01 534.50 0.3837E-03 0.6454E-01 534.50 0.3842E-03 0 .6 7 59E-01 621.25 0.3706E-03 0.6761E-01 621.25 0.3709E-03 0.7 216E-01 702.50 0.3915E-03 0.7181E-01 702.50 0.3861E-03

LEAST SQUARES RATE CONSTANT = 0.3789E-03 AVERAGE RATE CONSTANT = 0.3840E-03 CORRELATION COEFFIC I ENT a 0.9980 STANDARD DEVIATION FROM MEAN = 0.9261E-05 AMIDE CONCENTRATION = . 101 2N CATALYST CONCENTRAT ION * .1253N PERCENTAGE OF REACT ION FOLLOWED = 57.31

* / \ /C

METHOXYACETAMIDE AT 65 DEGS. RUN 2

CONCENTRATION T IME RATE CONSTANT 0.4353E-01 27O.OO 0.3930E-03 0.4349E-01 27O.OO 0.3923E-03 0.5072E-01 345.75 0.4038E-03 0.5047E-01 345.75 0.4001E-03 0.5460E-01 429.50 0.3765E-03 0.5466E-01 429.50 0.3774E-03 0.5999E-01 527.00 0.3770E-03 0.5981E-01 527.00 0.3743E-03 0.6467E-01 617.75 0.3867E-03 0.6425E-01 617.75 0.3802E-03 0.6817E-01 698.25 0.3950E-03 O.6737E-01 698.25 0.3820E-03

LEAST SQUARES RATE CONSTANT = 0.3784E-03 AVERAGE RATE CONSTANT = 0.3865E-03 CORRELATION COEFFIC I ENT = 0.9974 STANDARD DEVIATION FROM MEAN = 0.9638E-05 AMIDE CONCENTRATION = .O938N CATALYST CONCENTRAT ION = .1 253N PERCENTAGE OF REACTION FOLLOWED = Si .11

* •k METHOXYACETAMIDE AT 75 DEGS. RUN 1

CONCENTRAT ION TIME RATE CONSTANT 0.3947E-01 111.00 0.9377E-03 0.3878E-01 111.00 0 .9 1 15E-03 0.4626E-01 1it7.00 0.9303E-03 0.4606E-01 147.00 0.9230E-03 0.5328E-01 193.25 0.9312E-03 0 . 5332E-01 193.25 0.9326E-03 0.57 53 E—01 233.50 0.9108E-03 O.6213 E—01 283.50 0.9024E-03 0.6249E-01 283.50 0.9159E-03 0.7003E-01 387.25 0.9260E-03 O.6 9 7IE-01 387.25 0 .9 1 26E-03

LEAST SQUARES RATE CONSTANT = 0.9112E-03 AVERAGE RATE CONSTANT = 0.9212E-03 CORRELATION COEFFICIENT = 0.9997 STANDARD DEVIATION FROM MEAN = 0.1073E-04 AMIDE CONCENTRATION = . 1002N CATALYST CONCENTRATION = . 1050N PERCENTAGE OF REACTION FOLLOWED = 66.39

METHOXYACETAMIDE AT 75 DEGS. RUN 2

CONCENTRATION T IME RATE CONSTANT 0.3611E-01 97.75 0.9089E-03 0.3618E-01 97.75 0 .9 1 16E-03 O.4596E-OI 147.25 0.8996E-03 0.4595E-01 147.25 0.8996E-03 0.5352E-01 195.25 0.9102E-03 0.5830E-01 236.75 0.9048E-03 0.5840E-01 236.75 0.9083E-03 0.6606E-01 332.25 0.8829E-03 0.6639E-01 332.25 0.8953E-03 0.7049E-01 395.00 0.8996E-03 0.7014E-01 3 95.00 0.8860E-03

LEAST SQUARES RATE CONSTANT 0.8845E-03 AVERAGE RATE CONSTANT 0.9006E-03 CORRELATION COEFFICIENT 0.9998 STANDARD DEVIATION FROM MEAN 0 . 9132E-05 AMIDE CONCENTRATION . 1016N CATALYST CONCENTRATION .1050N PERCENTAGE OF REACTION FOLLOWED = 66.80 19 ISOBUTYRAMIDE AT 75 DEGS. RUN 3

TIME RESISTANCE RATE CONSTANT 32.75 63.80 0.6255E-03 61.75 67.10 0.6281E-03 100.25 71.50 0.6385E-03 137.50 75.60 0.6A35E-03 168.25 78.80 0.6A39E-03 22A.75 8A.20 0.6388E-03 270.25 88.60 0.6AA5E-03 30A.00 91.50 0.6429E-03 336.25 9A.20 0.6A28E-03 365.75 96.60 0.6A35E-03 A06.25 99.70 0.6437E-03 A38.00 102.00 0.6437E-03

LEAST SQUARES RATE CONSTANT = 0.6A60E-03 AVERAGE RATE CONSTANT = 0.6A00E-03 CORRELATION COEFFICIENT = 0 . 1000E+01 STANDARD DEVIATION FROM MEAN = 0.6191E—05 PREDICTED INFINITE RESISTANCE = 1 AO. 50 PREDICTED ZERO RESISTANCE = - 60.00 AMIDE CONCENTRATION = .093AN CATALYST CONCENTRATION = .036SN PERCENTAGE OF REACTION FOLLOWED = 71.87

ISOBUTYRAMIDE AT 75 DEGS. RUN A

TIME RESISTANCE RATE CONSTANT 32.25 6 A; AO 0 .7 172E-03 61.00 67.70 0.6712E-03 99.25 72; 10 0.6590E-03 138.00 75.80 0.6282E-03 167.50 79.AO 0.6A5AE-03 223.50 8A.80 0.63A3E-03 269.00 89:30 0.637 5E-03 302.75 92.10 0.630AE-03 33A.75 9 A. 90 0.6303E-03 365.00 97.20 0.6252E-03 A05.50 100.60 0.6285E-03 A37.00 102.80 0.62A6E-03 LEAST SQUARES RATE CONSTANT = 0.6162E-03 AVERAGE RATE CONSTANT = 0.6AA3E-03 CORRELATION COEFFICIENT = 0.9999 STANDARD DEVIATION FROM MEAN = 0.2590E-0A PREDICTED INFINITE RESISTANCE = 1A5.50 PREDICTED ZERO RESISTANCE = 60.00 AMIDE CONCENTRATION = .O93AN CATALYST CONCENTRATION = .O368N PERCENTAGE OF REACTION FOLLOWED = 70.85 20

ISOBUTYRAMI DE AT 85 DEGS. RUN 1

TIME RESISTANCE RATE CONSTANT 36.00 58.70 0 . 1339E-02 10A .00 64.00 0.1349E-02 160.75 67.80 0 ; 1346E-02 222.50 71.60 0.1361E-02 282.50 74.80 0.1364E-02 339.50 77.40 0.1355E-02 453.75 82.00 0.13 51E-02 500.25 83.60 0.1347E-02 553.00 85.70 0.137 5E-02 605.00 87.20 0.1368E-02 643.00 88.00 0.1347E-02 678.50 88.80 0.1335E-02

LEAST SQUARES RATE CONSTANT = 0.1354E-02 AVERAGE RATE CONSTANT = 0.13 53 E—02 CORRELATION COEFFICIENT = 0.9996 STANDARD DEVI AT I ON FROM MEAN = 0.1146E-04 CONCENTRATION OF REACTANTS = .0373N PREDICTED INF IN ITE RESISTANCE = 127.60 PREDICTED ZERO RESISTANCE = 55.56 PERCENTAGE OF REACTION FOLLOWED = 66.30

/\ /V

ISOBUTYRAMIDE AT 85 DEGS. RUN 2

TIME RESISTANCE RATE CONSTANT 35.00 60-.00 0.1381 E-02 103.75 65.40 0.1350E-02 159.75 69.50 0.1381 E-02 221.75 73.30 0.1378E-02 277.25 76.50 O'. 13 93 E—0 2 338.25 79.30 0.1376E-02 452.50 83.90 0.1361E-02 499.25 85.80 0 . 1376E-02 552.50 87.70 O.1303E-O2 601.25 89.40 0.1396E-02 643.25 90.20 0.1364E-02 677.50 91.20 0.1368E-02

LEAST SQUARES RATE CONSTANT = 0.1376E-02 AVERAGE RATE CONSTANT = 0.1376E-02 CORRELATION COEFFICIENT = 0.9997 STANDARD DEVIATION FROM MEAN = 0.1275E-04 CONCENTRAT ION OF REACTANTS = .0373N PREDICTED INFINITE RESISTANCE = 130.50 PREDICTED ZERO RESISTANCE = 56.78 PERCENTAGE OF REACTION FOLLOWED = 66.81 1SOBUTYRAM I DE AT 95 DEGS. RUN 1

TIME RESISTANCE RATE CONSTANT 24.75 58.50 0.2762E-02 61.00 64.00 0.2927E-02 98.00 68.50 0.2916E-02 136.25 72.40 0 . 2896E-0 2 180.50 76.40 O.29I2E-02 210.50 78.90 0.2946E-02 241.50 81 .00 0.2934E-02 272.50 82.80 0.2906E-02 3 0 1 .75 84.40 0.2892E-02 333.25 86.00 0 . 2883E-02 3 6 1 .25 87.40 0 . 2892E-0 2 395.00 88.80 0.2876E-02

LEAST SQUARES RATE CONSTANT = 0.2902E-02 AVERAGE RATE CONSTANT = 0.2895E-02 CORRELAT ION COEFFICIENT = 0.9996 STANDARD DEVIATION FROM MEAN = 0.4490E-04 CONCENTRATION OF REACTANTS = .0355N PREDICTED INFINITE RESISTANCE = 121.50 PREDICTED ZERO RESISTANCE = 54.53 PERCENTAGE OF REACTION FOLLOWED = 70.02

✓ \ /S A

ISOBUTYRAMIDE AT 95 DEGS. RUN 2

TIME RESISTANCE RATE CONSTANT 25-75 56-.80 O.3 OO6E-O2 62.25 62.00 0.2972E-02 99.00 66'. 40 O.297IE-0 2 136.50 70.40 0.3019E-02 180.25 74.10 O.3OO7 E-O2 210.50 76:60 0.3059E-02 242.25 78:50 0.3017E-02 272.75 80.40 0.3033E-02 301.25 81.80 O.30O6E-O2 333.50 83.30 0.2990E-02 361.25 84.50 0.2981E-02 395.00 85.90 0.2983E-02

LEAST SQUARES RATE CONSTANT = 0.3005E-02 AVERAGE RATE CONSTANT = 0.3004E-02 CORRELATION COEFFICIENT = 0.9996 STANDARD DEVIATION FROM MEAN = O .2 5 IIE -04 CONCENTRAT ION OF REACTANTS = .0373N PREDICTED INFI NITE RESISTANCE = 114.75 PREDICTED ZERO RESISTANCE = 52.38 PERCENTAGE OF REACTION FOLLOWED = 71.80 22

â-METHYLBUTYRAMIDE AT 75 DEGS. RUN 1

CONCENTRATION TIME RATE CONSTANT 0.2460E-01 297.50 0.1642E-03 0.2363E-01 297.50 0 .1 558E-03 0.4210E-01 646.75 0.1646E-03 0.4208E-01 646.75 0.1645E-03 0.4746E-01 800.25 0.1638E-03 0.4741E-01 800.25 0.1635E-03 0 .5 1 58E-01 912.00 0 . 1681E-03 0.4992E-01 912.00 0.1578E-03 0.6272E-01 1493.50 0.1570E-03 0.6313E-01 1493.50 0.1596E-03 0.6648E-01 1788.25 0 . 1523E-03 0.6620E-01 1788.25 0.1506E-03 O.6909E-OI 2021.25 0.1499E-03 0.7051E-01 2021.25 0 .1 592E-03

LEAST SQUARES RATE CONSTANT = 0 .1 503E-03 AVERAGE RATE CONSTANT = 0 .1593E-03 CORRELATION COEFFICIENT = O.998O STANDARD DEVIATION FROM MEAN = 0.5530E-05 AMIDE CONCENTRATION = . 1033N CATALYST CONCENTRATION = .10 50N PERCENTAGE OF REACTION FOLLOWED = 68.26

â-METHYLBUTYRAMIDE AT 75 DEGS. RUN 2

CONCENTRAT ION TIME RATE CONSTANT 0.2344E-01 300.50 0.1515E-03 0.2340E-01 300.50 0.1512E-03 0.4210E-01 652.75 0.1618E-03 0.4205E-01 652.75 0.1614E—03 O.49OOE-01 907.75 0 .1 517E-03 0.4929E-01 907.75 0.1534E-03 0.5792E-01 1208.00 0.1597E-03 0.5789E-01 1208.00 0 .1 595E-03 0.6253E-01 1482.50 0 .1 553E-03 0.6240E-01 1482.50 0.1545E-03 0 .6662E-01 1789.25 0.1512E-03 0.6670E-01 1789.25 0.1517 E—03 0.7049E-01 2037.25 0.1558E-03 0.6948E-01 2037.25 0.1493E-03 0.7437E-01 2453.00 0.1531E-03 0.7412E-01 2453.00 0.1515E-03 LEAST SQUARES RATE CONSTANT 0.1508E-03 AVERAGE RATE CONSTANT 0.1545E-03 CORRELATION COEFFICIENT O .9992 STANDARD DEVIATION FROM MEAN 0.3870E-05 AMIDE CONCENTRATION . 10 26N CATALYST CONCENTRATION .1050N PERCENTAGE OF REACTION FOLLOWED 72.24

/\ 23

â-METHYLBUTYRAMIDE AT 85 DEGS. RUN 1

CONCENTRATION TIME RATE CONSTANT 0 .2838E-01 165.00 0.3844E-03 0.28 31E—01 165.00 O.3 8 3 IE-0 3 0.43^*1 E-01 313.00 0.3S82E-03 0.4332E-01 313.00 0.3867E-03 0.5076E-01 466.00 O.347SE-O3 0.5804E-01 585.00 0.3682E-03 0.5703E-01 585.00 0.3538E-03 0.6627E-01 770.00 0.3910E-03 0 .6621E-01 770.00 0.3902E-03 0.7024E-01 32k.25 0.3872E-03 0.7040E-01 924.25 0.3901E-03 0.7308E-01 1066.50 0.3825E-03 0.7310E-01 1066.50 0.3828E-03 0.7639E-01 1204.25 0.3984E-03

LEAST SQUARES RATE CONSTANT = 0.3944E-03 AVERAGE RATE CONSTANT = 0.3810E-03 CORRELATION COEFFICIENT = 0.9982 STANDARD DEVIATION FROM MEAN = 0.1393E-04 AMIDE CONCENTRATION = .101 ON CATALYST CONCENTRATION = . 1050N PERCENTAGE OF REACTION FOLLOWED = 72.76

4.-METHYLBUTYRAMIDE AT 85 DEGS. RUN 2

CONCENTRATION TIME RATE CONSTANT 0.3012E-01 I 7 O.OO 0.3821E-03 0.3015E-01 170.00 O.3826E-O3 0.4607E-01 322.7 5 0.3903E-03 0.4576E-01 322.75 O.3858E-O3 0.5530E-01 474.00 0.3776E-03 0 ; 5523E-01 474.00 0.376 7E-03 0.6819E-01 763.00 0.3892E-03 0.6817E-01 763.00 0.3888E-03 0.7245E-01 923.25 0.3856E-03 0.7266E-01 923.25 0.3892E-03 0.7566E-01 1072.25 0.3840E-03 0.7563E-01 IO72 .2 5 0.3835E-03 0.77 53 E—01 1207.25 0.3729E-03 0.7738E-01 1207.25 0.3701E-03

LEAST SQUARES RATE CONSTANT 0.377 IE-03 AVERAGE RATE CONSTANT 0.3827E-03 CORRELATION COEFFICIENT 0.9992 STANDARD DEVIATION FROM MEAN 0.6067E-05 AMIDE CONCENTRATION .1061N CATALYST CONCENTRATION .1050N PERCENTAGE OF REACTION FOLLOWED = 73.70 * 24

â-METHYLBUTYRAMIDE AT 95 DEGS. RUN 1

CONCENTRATION TIME RATE CONSTANT 0.4413E-01 149.50 0.8474E-03 0;4398E-01 149.50 0.8423E-03 0.5651E-Ol 237.50 0 .8661E-03 0.5631E-01 237.50 0.8595E-03 0.6169E-01 297.25 0.8511E-03 0.6189E-01 297.25 0.8581E-03 0.6600E-01 356.25 0.8491E-03 0.6592E-01 356.25 0.8462E-03 0.6939E-01 411.00 0.8527E-03 O.696IE-01 iti 1.00 0.8612E-03 0.7425E-01 509.50 0.8624E-03 O ^O AE-O I 509.50 0.8535E-03 0.7650E-01 582.25 0.8446E-03 0.7642E-01 585.25 0.8368E-03 LEAST SQUARES RATE CONSTANT = 0-.8444E-03 AVERAGE RATE CONSTANT « 0.8522E-03 CORRELATION COEFFIC IENT = 0.9996 STANDARD DEVIATION FROM MEAN = 0.8168E-05 AMIDE CONCENTRATION . 1005N CATALYST CONCENTRATION = .1050N PERCENTAGE OF REACTION FOLLOWED = 72.78

«JU/\ Ve Ve

•METHYLBUTYRAM1 DE AT 95 DEGS. RUN 2

CONCENTRATION T IME RATE CONSTANT 0.3110E—01 82.50 0.8389E-03 0.3134E-01 8 2.50 0.8480E-03 0.4390E-01 139.50 0.8469E-03 0-. 4385E-01 139.50 0.8A55E-03 0.5640E-01 224.75 0.8492E-03 0.5633E-01 224.75 0.8468E-03 0.6286E-01 285.00 0.8608E-03 0.6304E-01 285.00 0.8669E-03 0.6705E-01 343-7 5 0.8452E-03 0.6721E-01 343.75 0.8509E-03 0.7114E-01 396.25 0.8721E-03 0.7050E-01 396.25 0.8481E-03 0.7516E-01 494.25 0.8382E-03 0.7530E-01 494.25 0.8434E-03 0.7878E-01 571.75 0.864IE-03 0.78A7E-01 571.75 0.8507E-03 LEAST SQUARES RATE CONSTANT 0.8535E-03 AVERAGE RATE CONSTANT = 0.8510E-03 CORRELATION COEFFICIENT = 0.9996 STANDARD DEVIATION FROM MEAN = 0 . 9544E-05 AMIDE CONCENTRATION = .1050N CATALYST CONCENTRATION = .1050N PERCENTAGE OF REACTION FOLLOWED = 74.73

«J- 25

ÇYCLOPENTANECARBOXAM1 DE AT 75 C RUN 1

TIME RESISTANCE RATE CONSTANT 59.00 62.40 0 .8065E-03 150.25 67.30 O.8807E-O3 224.50 70.60 0.8724E-03 310.75 74.30 0.8829E-03 ^05.25 78.00 0.8927 E-03 492.25 81.00 0.8945E-03 585.25 84.00 0.9002E-03 708.75 87.30 0.8929E-03 801.00 89.50 0.8873E-03 897.50 91.70 0 .8861E-03 1582.00 103.40 0.8869E-03 1684.00 104.60 0.8826E-03 1774.25 105.80 0.8877E-03 1872.75 106.80 0.8828E-03 1967.00 107.60 0.8740E-03 2055.75 108.50 0.8741E-03 LEAST SQUARES RATE CONSTANT = 0.8840E-03 AVERAGE RATE CONSTANT = 0.8803E-03 CORRELATION COEFFICIENT = 0:9996 STANDARD DEV I AT ION FROM MEAN = 0.2046E-04 CONCENTRAT ION OF REACTANTS = .0326N PREDICTED INF INITE RESISTANCE = 143.00 PREDICTED ZERO RESISTANCE = 59.36 PERCENTAGE OF REACTION FOLLOWED 77.43

/V *>'<■ Vs

CYCLOPENTANECARBOXAMI DE AT 75 C RUN 2

TIME RESISTANCE RATE CONSTANT 152.25 69.30 0.9086E-03 227.25 72.80 0.9044E-03 312.00 76; 90 0.9392E-03 A07.00 80.70 0.9438E-03 ASA.00 83.80 0.9450E-03 588.25 86.10 0.9075E-03 710.50 89.70 0:9147E-03 803.25 92.10 O.9I63E-03 899.50 94.40 0.9186E-03 1583.75 106.40 0.9296E-03 1686.00 107.60 0.9250E-03 1776.00 108.70 0.9262E-03 187A.75 109.90 0.9303E-03 1970.50 110.80 0.9251E-03 2058.25 111.40 0.9124E-03

LEAST SQUARES RATE CONSTANT z z 0.9235E-03 AVERAGE RATE CONSTANT = O.923IE-03 CORRELATION COEFFICIENT = 5 0.9994 STANDARD DEV LAT I ON FROM MEAN = 0 .1 248E-04 CONCENTRAT ION OF REACTANTS = s .0326N PREDICTED IMF INITE RESISTANCE = 144.90 PREDICTED ZERO RESISTANCE = 60.51 PERCENTAGE OF REACTION FOLLOWED = 78.19 26

CYCLOPENTANECARBOXAMIDE AT 85 C RUN 1

TIME RESISTANCE RATE CONSTANT 66.75 60. 60 O.I796E-O2 129.OO 66.00 O.I786E-O2 184.25 70.00 0.177 IE-02 243.00 73.50 0 . 1739E—02 305.00 77.20 0.1771E—02 364.75 80.20 0 . 17SIE-02 425.00 82.60 0 . 176IE—02 483.75 85.00 0.17 77 E—0 2 544.25 87.10 0.1779E-02 605.25 89.20 0 . 1801E-02 664.25 90.60 O.I7 76 E-O2 728.25 92.20 0 . 1774E-02 782.50 93.50 O.I7 7 8 E-O2 844.00 94.90 0 . 1787E-02 906.75 95.80 0 . 1753E-02

LEAST SQUARES RATE CONSTANT = o-. 1775E-02 AVERAGE RATE

CYCLOPENTANECARBOXAM1 DE AT 85 C RUN 2

TIME RESISTANCE RATE CONSTANT 69.25 62.40 0 . 1728E-02 132.25 68:10 0 . 1759E-02 187.50 72.10 0.1735E-02 245.50 76:00 O.I749E-O2 306.50 79.50 0.17 52E-02 367.50 82.40 0.17 37 E—0 2 427.50 85.10 0 . 1742E-02 486.75 87.60 O.I758 E-O2 545.50 89.80 O.I7 7 OE-O2 608.OO 91.60 0.1751E—02 665.50 93.20 O.I74 5 E-O2 730.00 94.90 0.1745E-02 784.50 96.20 0.1744E-02 845.75 97.60 0.1748E-02 908.75 98.70 0 . 1730E-02 LEAST SQUARES RATE CONSTANT = O .I74 7 E-O2 AVERAGE RATE CONSTANT = 0.1746E-02 CORRELATION COEFFICIENT = 0.9997 STANDARD DEVIATION FROM MEAN = 0.1077E-04 CONCENTRATION OF REACTANTS = .O3 7 IN PREDICTED INF IMITE RESISTANCE = 128.70 PREDICTED ZERO RESISTANCE = 55.06 PERCENTAGE OF REACTION FOLLOWED = 77.27 27

CYCLOPENTANECARBOXAMIDE AT 95 DECS. RUN

TIME RESISTANCE RATE CONSTANT 54.50 65.10 0.2912E-02 76.75 68.00 0.2834E-02 111.00 72.60 0.2917E-02 159.25 78.30 0.3037E-02 191.75 81.30 0.3046E-02 237.75 84.40 0.2956E-02 285.00 87.00 0.2865E-02 331.75 90.00 0.2919E-02 375.00 92.50 0 . 2973E-02 418.00 93.90 0.2888E-02 473.50 97.50 0.3135E-02 575.50 100.20 0.3028E-02 670.50 101.60 0.2831E-02

LEAST SQUARES RATE CONSTANT = 0 . 2953E- 0 2 AVERAGE RATE «CONSTANT = 0.2949E-02 CORRELATION COEFFICIENT = 0.9933 STANDARD DEVIATION FROM MEAN = 0.8762E-04 CONCENTRAT ION OF REACTANTS = .0382N PREDICTED IMF 1 N ITE RESISTANCE = 126.50 PREDICTED ZERO RESISTANCE = 55.62 PERCENTAGE OF REACTION FOLLOWED = 8O.77

✓\ /s sU

CYCLOPENTANECARBOXAM IDE AT 95 DEGS. RUN

TIME RESISTANCE RATE CONSTANT 30; 25 149;70 O.3OOOE-O2 62.25 I 6O.8O O.2836E-O2 92-.50 172; 10 0.3006E-02 123.7 5 180;60 O.2957E-O2 155.50 189.20 0.3007E-02 187.75 195.70 0.2953E-02 246.25 206.80 0.2955E-02 274.00 211.80 O.2987 E-02 322.00 219.00 0.3002E-02 364.00 223.30 0.2931E-02 401.75 228.60 0.2999E-02 435.75 231.10 0.2929E-02 471.00 234.60 0.2939E-02

LEAST SQUARES RATE CONSTANT = 0.2962E-02 AVERAGE RATE CONSTANT = 0.2962E-02 CORRELATI ON COEFFICIENT = 0.9993 STANDARD DEVIATION FROM MEAN = 0.4605E-04 CONCENTRAT ION OF REACTANTS = .036SN PREDICTED INFINITE RESISTANCE = 310.62 PREDICTED ZERO RESISTANCE = 136.02 PERCENTAGE OF REACTION FOLLOWED = 74.76

/V 28

CYCLOHEXANECARBOXAMIDE at 75 DECS RUN 1

TIME RESISTA RATE CONSTANT 32.25 159.60 0.4393E-03 112.00 165.80 0.4073E-03 223.50 174.20 0.4068E-03 302.00 180.00 0.4112E-03 352.00 183.10 0.4053E-03 423.00 187.70 0.4045E-03 583.00 1 97.80 0.4080E-03 723.25 205.90 0.4097E-03 1386.00 237.00 0.4136E-03 1473.50 239.80 0.4094E-03 1583.25 244.50 0.4144E-03 1672.25 247.50 0.4134E-03 1746.75 249.60 0.4104E-03 1860.00 252.80 0.4071E-03 2029.25 258.30 0.4093E-03 2147;00 262.20 0.4127E-03 2878.50 280.00 0.4110E-03 3144.00 285.60 0.4118E-03 3307.50 288.20 0.4082E-03 4276.50 303.40 0.4049E-03

LEAST SQUARES RATE CONSTANT = 0.4099E-03 AVERAGE RATE CONSTANT = 0;4109E-03 CORRELATION COEFFICIENT = 0.9999 STANDARD DEVIATION FROM MEAN = 0.7107 E-0 5 CONCENTRATION OF REACTANTS = .0368N PREDICTED INFINITE RESISTANCE = 405.00 PREDICTED ZERO RESISTANCE = 156.70 PERCENTAGE OF REACTION FOLLOWED = 78.87 29

CYCLOHEXANECARBOXAMIDE a t 75 DECS RUN 2

TIME resistance RATE CONSTAI! T 225.75 162.40 0.3915E-03 304.75 1 67.20 0.3878E-03 354.00 1/ 0.00 0.3348E-03 425.50 173.80 0.3798E-03 589.25 183.30 0.3901E-03 Til.SO 190.60 0.389SE-03 1389.25 217.00 0.3922E-03 1476.25 219.20 0.3 66E-03 1585.50 223.40 0.3924E-03 16 76.OO 225.20 0.3850E-03 1753.75 228.00 0.3891E-03 1863.00 231.00 0.3886E-03 2033.00 235.20 0;3S64E-03 2150.00 238.70 0.3903E-03 2666.25 249.00 0.3828E-03 2882.00 254.00 0.3 ' 9E-03 3150.00 258.60 0.3879E-03 3305.50 261.00 0 . 3867E-03 4278.50 274.80 0.33 9E-03

LEAST SQUARES RAIE CONSTANT = 0.3880E-03 AVERAGE RATE CONSTANT = 0.3879E-03 correlation coefficient = 0.9998 standard deviation from mean = 0.3140E-05 CONCENTRAT ION OF reactants = .0378N PREDICTED INFINITE RESISTANCE = 36U.25 PREDICTED ZERO RESISTANCE = 146.63 percentage OF REACTION FOLLOWED = 78.65 30

CYCLOH EXANECARBOXAM1DE AT 85 DECS RUM 1

TIME resistance RATE CONSTANT 67:50 150.60 0-.8378E-03 119:25 158.00 0.8886E-03 151.25 161.60 0.8699E-03 191:00 166.30 O.8729E-O3 271.00 174:60 0.8636E-03 333.00 181.70 0.8938E-03 370.00 184.20 0;8689E-03 43 3.25 190.60 0.8922E-03 554.25 200.00 0.8909E-03 648.00 205:70 0.8747E-03 720.75 210.10 O.8 7I2E-03 1443.50 242.00 0.8702E-03 1570:00 245.80 0.8682E-03 1623.00 247.20 0.8656E-03 1713.50 250.10 0.8733E-03 1799.50 253.60 0.8982E-03 LEAST SQUARES RATE CONSTANT = 0.8764E-03 AVERAGE RATE CONSTANT = O.875OE-03 correlati ON COEFFICIENT = 0.9995 standard deviation from mean = 0.1454E-04 concentration of reactants = .0368N predicted infinite resistance = 329.00 PREDICTED ZERO RESISTANCE = 141.30 percentage of reaction followed = 77.62

CYCLOHEXANECARBOXAMIDE AT 35 DECS RUN 2 TIME RESISTANCE RATE CONSTANT 69.75 144.80 0-.8731E-03 122:25 151:60 0.8919E-03 154:25 155.70 0 ; 9082E-03 192:25 160;00 0.9074E-03 273.75 168.30 0.9008E-03 330.00 173.80 0.9066E-03 372.50 177.10 0:8934 e-03 435.75 183.00 0 .9 1 14E-03 556.50 191.80 0.9073E-03 650.00 197.70 0.9022E-03 722.00 202.00 0.9022E-03 1445.00 2.52.00 0.8987E-03 1573:25 236.20 O.909OE-O3 1636.00 237.00 0.8905E-03 1715.50 239.50 0.9001E-03 1801.75 241.80 0.9046E-03

LEAST SQUARES RATE CONSTANT = O .9O16E-O3 AVERAGE RATE CONSTANT = 0.9005E-03 CORRELATION COEFFICIENT = 0.9999 STANDARD DEVI AT ION FROM MEAN = 0.9304E-05 CONCENTRAT ION OF reactants = .0368N PREDICTED INF IN ITE RESISTANCE = 312.00 PREDICTED ZERO RESISTANCE = 135.32 PERCENTAGE OF REACTION FOLLOWED = 77.76 31

cyclohexanecarboxamide at 95 DECS RUN 1

TIME RESISTANCE RATE CONSTANT 46.00 62.50 0 .1 8 37 E—0 2 95.25 67.10 0 .1 954E-02 131.50 70.50 0 . 206/E-02 177.00 73'.00 0.1937E-02 228.50 76.80 0.2044E-02 265.25 79.00 0 . 2073E-02 329.75 82.00 0.2059E-02 367.50 83.30 0.2018E-02 401.25 85.20 0.2098E-02 458.50 86.20 0 .1 961E-02 562.75 89.30 0 .1 959E-02 601.50 91.00 0.2049E-02 660.00 91.95 0.1989E-02 712.50 93.00 0 .19 7 7 E-02 870.00 96.20 0.2016E-02

LEAST SQUARES RATE CONSTANT 52 0.2011E-02 AVERAGE RATE CONSTANT = 0 ; 2006E-02 CORRELATION COEFFICIENT = 0.9971 standard d e v ia t io n from mean = 0.5779E-04 concentration OF REACTANTS = .0345N p r ed ic ted in f in it e resistance =s 118.75 predicted zero resistance ss 57.76 percentage of REACTION FOLLOWED 77.80

cyclohexanecarboxamide a t 95 DECS RUN 2

t ime RESISTANCE rate constant 32.00 100.00 0 . 2315E-02 60.00 103.40 0 .1 939E-02 104.00 110.00 0 .20 1 0E-02 146.25 115.30 0 . 2022E-02 173.00 119.60 0 .2 1 12E-02 226.00 124.60 0.21 37 E-02 272.25 129.30 0.2206E-02 319.00 131.20 0.2049E-02 361.75 135.40 0.2169E-02 405.50 137.50 0 .2 1 17E-02 462.00 140.30 0 . 2093E-02 555.25 144.00 0.2038E-02 658.00 148.40 0.2080E-02

LEAST SQUARES RATE CONSTANT ss 0 . 2095E-02 AVERAGE RATE CONSTANT ss 0.2099E-02 CORRELATION COEFFICIENT = O.9969 STANDARD DEVIAT I ON FROM MEAN = 0.9238E-04 concentration OF reactants = .0357N PREDICTED INF I MITE RESISTANCE ss 187.50 PREDICTED ZERO resistance = 93.33 PERCENTAGE OF REACTION FOLLOWED = 73.89

JU/\ w»-*\ 32

DIETHYLACETAMIDE AT 75 DEGS. RUN 1

CONCENTRATION TIME RATE CONSTANT 0 .3 4 5 8 E-01 3561 .75 0 . 1788E-04 0.3904E-01 4346.00 0.1752E -04 0.3929E-01 4346.00 0 . 1769E-0 4 0.4621E-01 5572.50 0 . 17 S7 E—04 0.4601E-01 5572.50 0 . 1774E-04 0.5269E-01 7042.00 0.1782E -04 0.525AE-01 7042.00 0 . 1772E-04 0 .5 7 ^ 1 E-01 8372.25 0 . 1769E-0 4 0 .5 7 4 8 E-01 8372.25 0.17 73 E—04 0.6237E-01 9940.50 0.17 73E-04 0.6240E-01 9940.50 0.1775E -04

LEAST SQUARES RATE CONSTANT = 0.1773E -04 AVERAGE RATE CONSTANT = 0.1774E -04 CORRELATION COEFFICIENT = 0.9999 STANDARD DEVIATION FROM MEAN = 0.9508E-07 AMIDE CONCENTRATION = . 1059N CATALYST CONCENTRATION = .1253N PERCENTAGE OF REACTION FOLLOWED = 49.80

Vc Vc •>'<

DIETHYLACETAMIDE AT 75 DEGS. RUN 2

CONCENTRATION TIME RATE CONSTANT 0-.3604E-01 3535.75 0 . 1785E-04 0 .3 5 7 1 E-01 3535.75 0 .17 6 1 E-04 0.4104E-01 4314.25 0 . 1774E-04 0 .4 0 8 9 E-01 4314.25 0.1764E -04 0 .4 8 1 7 E-01 5545.50 0 . 1785E-04 0.4813E-01 5545.50 0 . 1783E-0 4 0.5474E-01 7056.00 0 . 1760E-04 0 .5 4 8 3 E-01 7056.00 0 . 1765E-0 4 0.5973E-01 8367.00 0.17 58E-04 0.5974E-01 8367.00 0.1759E -04 0 .6 4 5 8 E-01 9939.25 0 . 1746E-04 0.6474E-01 9939.25 0 . 1756E-04

LEAST SQUARES RATE CONSTANT z s 0 . 1738E-04 AVERAGE RATE CONSTANT = 0.1766E -04 CORRELATION COEFFICIENT = 0.9999 STANDARD DEVIATION FROM MEAN S3 0 .1 208E-06 AMIDE CONCENTRATION = . 1119N CATALYST CONCENTRATION =3 .1253N PERCENTAGE OF REACTION FOLLOWED = 51.67

/v 33

D 1ETHYLACETAM1 DE AT 85 DEGS. RUN 1

CONCENTRAT ION T IME RATE CONSTANT 0.4757 E—01 2517.00 0.4354E -04 0.4776E-01 2517.00 0.4384E -04 0 .5 3 2 3 E-01 2986.25 0.4498E -04 0.5321E-01 2986.25 0.4496E -04 0 .6 0 6 1 E-01 3999.50 0 .4 3 7 1E-04 0.6050E-01 3999.50 0.4354E -04 0 .6 9 9 7 E-01 5485.00 0.4500E -04 0.7004E-01 5485.00 0.4510E -04 0.7589E-01 7020.00 0.4443E -04 0.7583E-01 7020.00 0.4432E -04 0 .8 2 8 9E-01 9708.25 0.4374E -04 0.8309E-01 9708.25 0.4417E -04 LEAST SQUARES RATE CONSTANT = 0.4403E -04 AVERAGE RATE CONSTANT = 0.4428E -04 CORRELATION COEFFICIENT = 0.9997 STANDARD DEVIATION FROM MEAN = 0.5833E-06 AMIDE CONCENTRATION = . 1029N CATALYST CONCENTRATION = .1253N PERCENTAGE OF REACTION FOLLOWED = 66.31

•ju A A /\

DlETHYLACETAMIDE AT 85 DEGS. RUN 2 CONCENTRAT ION TIME RATE CONSTANT 0.4945E-01 2503.00 0.4686E -04 0.4916E-01 2503.00 0.4638E -04 0.5302E-01 2972.OO 0.4487E -04 0.5298E-01 2972.00 0.4479E -04 0.6195E-01 3975.00 0.4616E -04 0 . 6163E—01 3975.00 0.4563E -04 0.6999E-01 5471.50 0.4513E -04 0.6982E-01 5471.50 0 .4484E-04 0.7599E-01 7006.25 0.4470E -04 0 .7 6 0 1 E-01 7006.25 0.4474E -04 0.8186E-01 8449.50 0.4788E -04 0.8217E-01 8449.50 0.4859E -04 0.8309E-01 9708.25 0.4417E -04 0 .8289E-01 9708.25 0.4374E -04

LEAST SQUARES RATE CONSTANT = 0.4530E -04 AVERAGE RATE CONSTANT = 0.4560E -04 CORRELATION COEFFICIENT = 0.9957 STANDARD DEVI AT ION FROM MEAN = 0 . 1355E-05 AMIDE CONCENTRATION = .1029N CATALYST CONCENTRATION = -1253N PERCENTAGE OF REACTION FOLLOWED = 66.15 34

DIETHYLACETAMIDE AT 95 DEGS. RUN 1

CONCENTRATION T IME RATE CONSTAN 0.4538E-01 906.00 0.1073E -03 0.4540E-01 906.00 0.1074E-03 0-.5949E-01 1516.00 0.1057E-03 0.5920E-01 1516.00 0.1046E-03 0 .6 9 1 6E-01 217 2.00 0 . 1042E-03 0 .6876E-01 2172.00 0.1027E-03 0.7459E-01 2721.00 0 .1 022E-03 0.7456E-01 2721.00 0.1020E-03 0.7890E-01 3278.50 0.1008E-03 O.83OIE-01 3900.00 0.1013 E—03 0.8580E-01 4475.25 0.1006E-03 0.8577E-01 4475.25 0.1004E-03 LEAST SQUARES RATE CONSTANT = 0.9855E-04 AVERAGE RATE CONSTANT = 0.1033E-03 CORRELATION COEFFICIENT = 0 .99 99 STANDARD DEVI AT ION FROM MEAN = 0.2425E-05 AMIDE CONCENTRATION = .1 270N CATALYST CONCENTRATION = .1050N PERCENTAGE OF REACTION FOLLOWED = 81.69 •X,y\ _ ^ /v -U *\ DIETHYLACETAMIDE AT 95 DEGS. RUN 2

TIME RESISTANCE RATE CONSTANT 98.00 56.62 0 .8464E-04 269.00 60.42 0.1058E-03 369.00 62.09 0.1020E-03 435.25 63.32 0 . 1022E-03 585.50 66.30 0.1054E-03 68 5.7 5 68.34 0.1079E-03 1417.50 79.36 0 . 1055E-03 1530.00 80.96 0 . 106 IE-03 1612.00 81.96 0 . 1058E-03 1721.50 82.83 0.1034E-03 1805.25 84.00 0.1043E-03 1867.00 85.00 0 . 1057E-03 2059.00 86'. 96 0.1050E-03 2893.50 94.05 0.1037 E—03 2978.00 94.91 0.1049E-03 3040.00 95.81 0 . 1074E-03 3294.00 96.85 0.1044E-03

LEAST SQUARES RATE CONSTANT = 0.1053E-03 AVERAGE RATE CONSTANT = 0.1038E-03 CORRELATION COEFFICIENT = 0.9997 STANDARD DEVIATION FROM MEAN = 0.5017E-05 PREDICTED INFINITE RESISTANCE = 108.78 PREDICTED ZERO RESISTANCE = 55.00 AMIDE CONCENTRATION = .1248N CATALYST CONCENTRATION = .0347N PERCENTAGE OF REACTION FOLLOWED = 87.41 35

TRIMETHYLACETAMIDE AT 65 DECS. RUN 1

CONCENTRAT ION T IME RATE CONSTANT 0.4870E-01 1162.00 0.9657E -04 0.4862E-01 1162.00 0.9628E -04 0;548 IE-01 1427.75 0.97 67E-04 0.5473E-01 1427.75 0.9736E -04 0 . 589IE-01 1655.25 0.9732E -04 0.5862E-01 1655.25 0.9634E -04 0.6771E-01 2288.75 0.9642E -04 0.6752E-01 2288.75 0.9575E -04 0 .7 1 53E-01 2675.25 0.9506E -04 0 .7 1 4 1 E-01 2675.25 0.9466E -04 0.7393E-01 2959.00 0.9423E -04 0.7393E-01 2959.00 0.9423E -04

LEAST SQUARES RATE CONSTANT 0.9252E-04 AVERAGE RATE CONSTANT 0.9599E-04 CORRELATION COEFFICIENT 0.9997 STANDARD DEVIATION FROM MEAN 0 .1 1 59E-05 AMIDE CONCENTRATION . 1131N CATALYST CONCENTRATION . 113 4N PERCENTAGE OF REACTION FOLLOWED = 65.37 *

TRIMETHYLACETAMIDE AT 65 DEGS. RUN 2

CONCENTRATION T IME RATE CONSTANT 0.3964E-01 845.25 0.9608E -04 0-.3958E-01 845.25 0.9587E -04 0 ; 4794E-01 1167.00 O.949IE -04 0.4783E-01 1167.00 0.9453E -04 0 .5 3 5 1 E-01 1423.50 0.9499E -04 0 . 5365E-01 1423.50 0 .95 4 8 E-04 0.5788E-01 1652.50 0.9554E -04 0.5780E-01 1652.50 0.9528E -04 0.6642E-01 2266.25 0.9463E -04 0.6629E-01 2266.25 0.9416E -04 0.7330E-01 2953.25 0.9402E -04 0.7324E-01 2953.25 O.938IE -0 4 LEAST SQUARES RATE CONSTANT = 0.9320E -04 AVERAGE RATE CONSTANT = 0.9494E -04 CORRELATION COEFFICIENT = 0.9999 STANDARD DEVIATION FROM MEAN = 0.7018E -06 AMIDE CONCENTRATION = .1131N CATALYST CONCENTRATION = . 11 28N PERCENTAGE OF REACTION FOLLOWED = 64.76 * ■>v 36

TRIMETHYLACETAMIDE AT 75 DECS . RUN 1

CONCENTRAT ION TIME RATE CONSTANT 0.2978E-01 176.25 0.2225E -03 0 .2 9 6 8 E-01 176.25 0 .2 2 1 5E-03 0 .3 9 4 1 E-01 265.00 O.2 1 7 IE-0 3 0.3959E-01 265.00 0.2186E-03 0.4842E-01 354.00 0.2223E-03 0.4818E-01 354.00 0.2205E-03 0.5451E-01 440.75 0.2178E-03 0.5476E-01 440.75 0 .2 1 95E-03 0.6105E-01 540.25 0.2186E-03 0.6132E-01 540.25 0.2205E-03 0.6546E-01 611.75 0.2218E-03

0.6523E-01 611.75 0 . 2202E-03 0.6935E-01 690.75 0.2222E-03 O.6896E-OI 690.75 0 .2 1 94E-03 LEAST SQUARES RATE CONSTANT = 0.2209E-03 AVERAGE RATE CONSTANT = 0.2202E-03 CORRELATION COEFFIC 1 ENT = O.9998 STANDARD DEVIATION FROM MEAN = 0.1697E-05 AMIDE CONCENTRATION = .1492N

CATALYST CONCENTRAT ION = . 1131N PERCENTAGE OF REACT ION FOLLOWED = 60.97

rk A A

TRIMETHYLACETAMIDE AT 75 DEGS . RUN 2

CONCENTRAT ION TIME RATE CONSTANT 0.3024E-01 179.50 0.2210E-03 0.3000E-01 179.50 0.2188E-03 0.4108E-01 270.75 0.2238E-03 0 .4 1 14E-01 270.75 0.2242E-03 0 .5 1 7 1 E-01 384.25 0.2261E-03 0.5172E-01 384.25 0.2262E-03 0.5969E-01 497.50 0.2252E-03 0 .5 9 7 3 E-01 497.50 0.2255E-03 0.6639E-01 608.00 0.2274E-03 0.6656E-01 608.00 0.2287E-03 0.7014E-01 684.00 0.2277E-03 0.6996E-01 684.00 0.2264E-03

LEAST SQUARES RATE CONSTANT 0.2299E-03 AVERAGE RATE CONSTANT = 0.2251E-03 CORRELATION COEFFICIENT = 0.9999 STANDARD DEVIATION FROM MEAN = 0.2709E -05 AMIDE CONCENTRATION = .1 503N CATALYST CONCENTRATION .113 IN PERCENTAGE OF REACT ION FOLLOWED = 61.86

/> ■>v 37

TRIMETHYLACETAMI DE AT 85 DEGS. RUN 1

CONCENTRATION T IME RATE CONSTANT 0.3347E-01 89.50 0 .5 1 15E-03 0.3332E-01 89.50 0.5083E-03 0.4443E-01 133.25 0.5156E-03 0.4429E-01 133.25 0.5133 E—03 0 .5 3 28E-01 178.25 0.5172E-03 0.5310E-01 178.25 0 .5 1 40E-03 0 .6 5^f 5E—01 261.00 0.5188E-03 O.6517 E—01 261.00 0.51M+E-03 0 .7 0 1 9E -01 304.50 0 .5 1 66E-03 O.7OI7 E—01 304.50 0.516AE-03 0.7A38E-01 352.00 0 .5 1 15E-03 0 .7447E-01 352.00 0.5130E-03

LEAST SQUARES RATE CONSTANT 0 .5 1 48E-03 AVERAGE RATE CONSTANT 0.5142E-03 CORRELATION COEFFICIENT 0.9999 STANDARD DEVIATION FROM MEAN 0.2796E-05 AMIDE CONCENTRATION .1 500N CATALYST CONCENTRATION .113 IN PERCENTAGE OF REACTION FOLLOWED = 65.85

TRIMETHYLACETAMIDE AT 85 DEGS. RUN 2

CONCENTRATION TIME RATE CONSTANT 0 ; 4291E-01 135.75 O.5O66E-O3 0.4291E-01 135.75 0.5067E-03 0 .5 1 91E-01 181.75 0 .5 1 36E-03 0 .5 1 95E-01 181.75 0.5141E-03 0 .5 8 1 OE-O1 221.25 0 .5 1 54E-03 0.5810E-01 221.25 0 .5 1 55E-03 0.6285E-01 261.00 0.5085E-03 0.6319E-01 261.00 0 .5 1 1+0E-03 0.6769E-01 303.00 0 .5 1 1AE-03 0.6729E-01 303.00 0.5050E-03 0.7228E-01 350.75 0 .5 1 28E-03 0.7237E-01 350.75 0.51 if^+E—03 LEAST SQUARES RATE CONSTANT 0.5130E-03 AVERAGE RATE CONSTANT = 0 .5 1 15E-03 CORRELATION COEFFICIENT = 0.9997 STANDARD DEVIATION FROM MEAN = 0.3630E-05 AMIDE CONCENTRATION = .1A35N CATALYST CONCENTRATION = . 1131N PERCENTAGE OF REACTION FOLLOWED = 63.99 38

2 .2-DIMETHYLBUTYRaMI DE AT 75 DECS. 1

TIME r e s is ta n c e rate constant 1427.25 61.30 0.5646E -05 2870.25 62.00 0 .5 6 1 2E-05 5847.25 63.40 0.5555E -05 1 1736.00 66.10 0.5549E-05 17327.00 68.40 0.5431E -05 20175.00 69.70 0.5502E-05 23033.00 71.00 0.5563E -05 28855.00 73.30 0.5537E-05 34572.00 75.50 0.5528E-05 40332.00 77.80 0.5585E-05 44653.00 79.30 0.5561E-05 48982.00 80.60 0.5488E-05

LEAST SQUARES RATE CONSTANT = 0.5533E-05 AVERAGE RATE CONSTANT = 0.5547E-05 CORRELATION COEFFICIENT = 0.9999 standard d e v ia t io n from mean = 0.543 E-07 concentration OF reactants = .0369N PREDICTED INFI NITE RESISTANCE = 187.00 PREDICTED ZERO r e s is ta n c e = 60.59 PERCENTAGE OF REACTION FOLLOWED = 36.72

2.2-DIMETHYLBUTYRAMIDE AT 75 DECS. 2

TIME r e s is ta n c e RATE CONSTANT 302.50 42.20 0.6167E-05 1426.50 42.70 0.7465E-05 2870.25 43.10 0.6189E-05 5847.25 43.90 0.5513E-05 11733.00 45.90 0.5958E-05 I 7 3 2 7 .OO 47.70 0 . 6102E-05 23032.00 49.20 0.5953E-05 28859.00 51.00 0 .6 1 24E-05 34575.00 52.50 0.6117 E—05 40335.00 53.90 0.6087E-05 44655.00 54.80 0.6006E-05 48982.00 55.80 0.6008E-05

LEAST SQUARES rat e constant = 0.6045E-05 AVERAGE RATE constant = 0 .61 4 1 E—0 5 correlation coefficient = 0.9997 standard d e v ia t io n from mean = 0.4340E-06 concentration of reactants = .0 3 69N PREDICTED INFINITE RESISTANCE = 114.30 PREDICTED ZERO RESISTANCE = 42.09 PERCENTAGE OF REACTION FOLLOWED = 38.88 39

2 .2-DIMETHYLBUTYRAMI DE AT 35 DECS. 1

TIME RESISTANCE RATE CONSTANT 1400.25 39.20 0.210 E-OA 2825.50 40.30 0.1925E -04 5838.50 42.60 0 .1 885E-04 8665.00 4 4.7 0 0 .1 9 1 2E-04 11531.00 47.00 0 .2 0 1 8E-04 14443.50 48.70 0.1986E -04 17300.00 50.20 0.1956E -04 20127.00 51.60 0 .1 937E-04 23003.00 53.10 0 .1 953E-04

LEAST SQUARES RATE CONSTANT = 0.1956E-04 AVERAGE RATE CONSTANT = 0.1964E-04 CORRELATION COEFFICIENT = 0.9993 STANDARD DEVIATION FROM MEAN = 0.6267E-06 concentration of reactants = .0369N PREDICTED INFINITE RESISTANCE = 91.30 PREDICTED ZERO RESISTANCE = 37.83 PERCENTAGE OF REACTION FOLLOWED = 49.10

•A./V ^ ^ A

2.2-DIMETHYLBUTYRAMIDE at 85 DEGS. 2

TIME r e s is ta n c e RATE CONSTANT 523'. 50 58; 60 0.1981E-04 1402;50 59.90 0 ; 2079E-04 2854;25 61 ; 90 0 . 2079E-04 5841 '.00 65.50 0 ;2 0 1 9E-04 8669;25 68; 40 0.1956E -04 11537;00 72.00 0 ; 2082E-04 14447;50 75.20 0.2145E -04 17303.00 77.10 0 . 2050E-04 20130.00 78.90 0 . 1987E-04 23007.00 81.60 0.2057E -04

LEAST SQUARES RATE CONSTANT = 0.2047E-04 AVERAGE RATE CONSTANT = 0.2044E-04 CORRELATION COEFFICIENT = 0.9987 STANDARD DEVIATION FROM MEAN = 0.5452E-06 CONCENTRATION OF REACTANTS = .0369N PREDICTED INFINITE RESISTANCE = 136.85 PREDICTED ZERO RESISTANCE = 57.86 PERCENTAGE OF REACTION FOLLOWED = 50.40 4 0

DIMETHYLBUTYRAMIDE AT 95 DECS. 1

T IME RESISTANCE RATE CONSTANT 547.50 54.30 0.6274E -04 732.75 55.00 0.6238E -04 1424.75 57.20 0 .5 8 1 5E-04 1597.00 58.00 0.6070E -04 1742.25 53.70 0.6286E-04 1903.25 59.10 0.6138E-04 2107.50 59.70 0.6071E-04 2873.75 62.20 0.6140E -04 3638.50 64.00 0.5873E -04 4313.00 66.30 0.6131E-04 5861.00 70.80 0.6406E-04 7276.25 73.20 0.6075E-04 8686.25 75.90 0.6035E-04

LEAST SQUARES RATE CONSTANT = 0.6112E-04 AVERAGE RATE CONSTANT = 0.6120E-04 correlation COEFFICIENT = 0.9986 STANDARD DEVIATION FROM MEAN = 0.1559E-05 CONCENTRATION OF REACTANTS = .0368N PREDICTED INFINITE RESISTANCE = 128.40 PREDICTED ZERO re s is ta n c e = 52.10 PERCENTAGE OF REACTION FOLLOWED = 52.77

•W.U -

DIMETHYLBUTYRAMIDE AT 95 DEGS. 2

TIME r e s is ta n c e RATE CONSTANT 307.50 52.70 0.67 91 E-04 548;25 53; 40 0.6051E-04 732.50 54.00 0.5999E -04 1426.00 56.40 0.6259E-04 1596.50 57.20 0.6589E-04 1744.00 57.40 0.6265E-04 1902.75 57.90 0 . 6282E-04 2107.25 58.40 0.6169E-04 2873.50 60.90 0 . 6446E-04 3639.75 62.60 0 . 6206E-04 4313.00 64.30 0.6244E -04 5860.75 67.90 0.6344E-04 7276.25 70; 60 0.6320E-04 8686.50 72.90 0.6262E -04

LEAST SQUARES RATE CONSTANT = 0.6294E-04 AVERAGE RATE CONSTANT = 0.6302E-04 CORRELATION COEFFICIENT = 0.9997 STANDARD DEVIA T 1 ON FROM MEAN = 0.1955E-05 concentration of reactants .0367N PREDICTED INFINITE RESISTANCE 114.00 PREDICTED ZERO RESISTANCE 51.47 PERCENTAGE OF REACTION FOLLOWED 53.59 41

RESULTS FROM AUTHOR’ S HONOURS THESIS

CHLOROACETAMIDE

TEMPERATURE RATE CONSTANT x 1C

5 5 .0 2.17 65.0 5.52 7 5 .0 11.8

BROMOACETAMIDE TEMPERATURE RATE CONSTANT x 1C A5.C 0.792

5 5 .0 2.11

65.0 A .71

N-VALERAMIDE TEMPERATURE RATE CONSTANT X 1C

5 5 .0 1.07 65.0 2.66

75.0 5.79

3.3-DIMETHYIBUTYRAMIDE TEMPERATURE RATE CONSTANT X 1C

7 5 .0 C. 188

85.0 0.451 95.0 0.990 42

RESULTS FROM PREVIOUS WORKERS

ACETAMIDE „ 4 TEMPERATURE RATE CONSTANT X 1C

55.0 1.77 65. C 4.30

75. C 10.3

PROP IONAMIDE 4 TEMPERATURE RATE CONSTANT X 10 65. C 5.64

75.0 12.0 85.0 26.9

BUTYRAMIDE 4 TEMPERATURE RATE CONSTANT X 10 65.0 2.56 75.0 5.99 85.0 13.0

* BOLTON,P.D. AUST. J_. CHEM.. 1966 L2, 1013-21 43

BASIC HYDROLYSIS OF ALIPHATIC AMIDES

AMIDE TEMPERATURE RATE CONSTANT X 1 . 0 a c e ta m id e 65. c 7.74 (- G. G1 ) 75. c 13.6 ( n oi ) 85. G 24.6 ( r*w . nrvO \J

PROPIONAMIDE 7 5 .G 13.1 ( n\J 0 nnOW KJ O }/ r» ni A 85. G 25.5 ( \j . yj Ì J 95 . 0 4 4 .G ( n ne \

BUTANAM IDE 75.0 7.05 ( ^ . vv*+ / 85. G 12.3 ( C.C2) 95.0 22.5 ( C.C3)

VALERAMIDE 75.0 5.52 ( nvy . nvy iI \) 85. G 10.9 ( r\\j . ni\yj \ } 95. G 18.2 ( oyj . nyj¿. i) J

1SO-VALERAMIDE 7 5.0 1.97 ( G. 1C) 85. G 4.03 ( G .15) 95.0 8.14 ( G .13)

PHENYLACETAMIDE 7 5 .G 17.7 ( nvy . nvy i| /\ 85. G 29.4 ( r»yj . 03vy.5 \) 9 5 .G 47.3 ( C.C6)

CYCLOHEXYLACETAMIDE 7 5 .G 1.77 ( G.G2) 85. G 3.94 ( C.C8) 95.0 6.80 ( C.C8)

METHOXYACETAMIDE 3 5 .G 8.56 ( C.C4) 45. G 18.6 ( nvy . yj 1 / \ 5 5 .G 34.7 ( yjrt . yj ni \ )J

CYCLOHEXANECARBOXAMIDE 75.0 4.24 ( C.C8) 85. G 6.22 ( G. 11 ) 95. G 12.2 ( C.C2)

CYCLOPENTANECARBOXAMIDE 7 5 .G 7.8C ( G .23 ) 85. G 13.6 ( nvy , noyjj \J 95. G 27.3 ( G.Cl ) o¿-METHYLBUTYRAMIDE 7 5 .G 1.65 ( G .09) 85. G 3.38 ( G.C6) 95. G 5 .7 9 ( C.C9)

ISO-BUTYRAMIDE 75.0 6 . 6l ( C.C6) 85. G 11.0 ( nvy , nvy iI ) \ 95.0 19.6 ( nvy . nyj oL )\

TRIMETHYLACETAMIDE 7 5.0 2.57 ( C.C4) 85. G 5.08 ( G .15) 95.0 10.3 ( 0 .1 2 ) 44

ACETAMIDE AT 65 DEGS. RUN 1

TIME RESISTANCE RATE CONSTANT 3 0.7 5 75.40 0.7683E-03 61.25 78.40 0.7651E-03 93.00 81.60 0.7839E-03 124;25 84.30 0.7723E-03 159.50 87.40 0.7759E-03 186.75 89.70 0.7783E-03 21 A .00 91.90 0.7796E-03 253.00 94.70 0.7724E-03 282.25 96.80 0 .77 1 8E—03 316.50 99.40 0.7800E-03 345.00 101.20 0.7762E-03 379.75 103.40 0.77 53E-03 414.25 105.40 0:7716E-03 442.75 107.20 0.77 52E-03

LEAST SQUARES RATE CONSTANT = 0:7752E-03 AVERAGE RATE CONSTANT = 0-.7747E-03 CORRELATION COEFFICIENT = 0:9999 STANDARD DEVIATION FROM MEAN = 0 .47 6 1 E-0 5 CONCENTRATION OF REACTANTS = .0505N PREDICTED INF INITE RESISTANCE = 204:00 PREDICTED ZERO RESISTANCE = 72 .20 PERCENTAGE OF REACTION FOLLOWED = 50.53 JLA X A 'k

ACETAMIDE AT 65 DEGS. RUN 2

TIME RESISTANCE RATE CONSTANT 34:25 76:90 0.7593E-03 59.25 79:30 0 :7 6 1 1E-03 91:25 82:40 0.7773E-03 123.75 85:30 0.7788E-03 159.50 88:30 0 :7 7 8 2E-03 185.25 90.40 0.7798E-03 213.00 92:50 0.7775E-03 251.25 95.00 0.7639E-03 280.50 97.20 0.7706E-03 315.25 99:70 0.7772E-03 343.50 101.40 0.7728E-03 378.50 103.50 0.7709E-03 412.75 105.50 0.7703E-03 441.00 107.30 0.7766E-03

LEAST SQUARES RATE CONSTANT = 0.7733E-03 AVERAGE RATE CONSTANT = 0.7724E-03 CORRELATION COEFFICIENT = 0:9999 STANDARD DEVIATION FROM MEAN = 0.6560E-05 CONCENTRATION OF REACTANTS = .0498N PREDICTED INFINITE RESISTANCE = 198:00 PREDICTED ZERO RESISTANCE = 73.47 PERCENTAGE OF REACTION FOLLOWED = 50.13

* * /V 45

ACETAMIDE AT 75 DEGS . RUN 2

TIME RESISTANCE RATE CONSTANT 32.00 7 0.5 0 0.1339E -02 60.00 74:60 0 : 1363E-0 2 93-75 79:20 0 : 1380E-0 2 126.00 82:90 0 . 1358E-0 2 156.50 86:50 0.1374E -02 183.50 89:20 0 : 1365E-0 2 227.50 93:30 0 . 1356E-0 2 264.00 96:80 0 : 1375E-02 303:25 99.80 0.1364E -02 336:75 102.30 0 : 1363E-0 2 365.00 104:30 0 : 1363E-0 2 391.75 106:20 0 : 1369E-0 2 421:25 107:80 0 : 1355E-02 453.50 110.00 0 . 1369E-0 2

LEAST SQUARES RATE CONSTANT = 0.1365E-02 AVERAGE RATE CONSTANT = 0-.1364E-02 CORRELAT 1ON COEFFICIENT = 0:9999 STANDARD DEVIATION FROM MEAN = 0.9803E-05 CONCENTRATION OF REACTANTS = .0499N PREDICTED INFINITE RESISTANCE = 175:50 PREDICTED ZERO RESISTANCE = 65.58 PERCENTAGE OF REACTION FOLLOWED = 64.47

k k k

ACETAMIDE AT 75 DEGS. BASIC TITRATION RUN

CONCENTRATION TIME RATE CONSTANT 0 . 1705E-01 59.00 0:137 5E-02 0.1710E-01 59:00 0 . 1380E-02 0.2575E-01 106:50 0 : 1382E-02 0.2623E-01 106.50 0.1424E -02 0.3036E-01 138:25 0 : 1405E-02 0.3002E-01 138.25 0.1377E -02 0.3463E-01 181.00 0.1376E -02 0:3458E-01 181:00 0.1373E -02 0.3785E-01 228.50 0 .1 3 1 5E-02 0 .3 8 1 9E-01 228.50 0 : 1342E-02 0.4233E-01 295.50 0 : 1328E-0 2 0.4254E-01 295.50 0.1346E -02 0.4433E-01 339.00 0:131 IE-02 0.4441E-01 339.00 0.1318E -02

LEAST SQUARES RATE CONSTANT s 0 : 1367E-0 2 AVERAGE RATE CONSTANT = 0 . 136IE-0 2 CORRELATION COEFFICIENT = 0:9995 STANDARD DEVIATION FROM MEAN = 0.3339E -04 AMIDE CONCENTRATION ss .071ON CATALYST CONCENTRAT ION S3 .067 IN PERCENTAGE OF REACT ION FOLLOWED S3 66.19

«A. * /V n 46

ACETAMIDE AT 75 DEGS. CHECK RUN 1 TIME RESISTANCE RATE CONSTANT 32.00 51.30 0.13S2E-02 61.00 54.80 0.1398E-02 89; 25 57 ;80 0.13998-02 122.00 61.00 0-.1413E-02 150.75 63.30 0.1396E-02 185.75 6 5 -.8 O 0 . 1380E-02 219.25 68.30 0.1403E-02 243.00 69.80 0.1405E-02 2 7 0 . 5 0 71.30 0.1397E-02 300.50 73.00 0.1406E-02 331.75 74.20 0 .1377E-02 364.50 75.90 0". 1397E-02 408;00 77.80 0.1407E-02 446.50 79.10 0.1396E-02

LEAST SQUARES RATE CONSTANT ss 0.1397E-02 AVERAGE RATE iCONSTANT ss 0; 1397E-02 CORRELATION COEFFICIENT =5 0.9997 STANDARD DEVIATION FROM MEAN SS 0.1032E-04 CONCENTRATION OF REACTANTS ss .O6 5 8 N PREDICTED INF INITE RESISTANCE ss 110.50 PREDICTED ZERO RESISTANCE = 47.01 PERCENTAGE OF REACTION FOLLOWED ss 70.61

ACETAMIDE AT 75 DEGS. CHECK RUN 2 TIME RESISTANCE RATE CONSTANT 28 ; 7 5 29; 10 0.1383E-02 47:00 31.70 0 .1 4 1 5E-02 62.75 33:60 0.1413E-02 78.25 35:20 O'. 1397E-02 90.50 36.50 0.141 IE-02 108.75 38.20 0.1417 E-0 2 119.75 39.20 0 . 1430E-02 155.75 41.70 0 . 1410E-02 173.75 42.80 0.1405E-02 190.75 43.80 0.1406E-02 211.75 44.90 0 .1 404E-02 253.00 46.80 0 .1 402E-02 RATE CONSTANT ss 0.1408E-02 ONSTANT S3 0 .14 0 8 E -02 ¡EFFICIENT s 0-.9996 JION FROM MEAN ss 0 . 1 104E-04 OF REACTANTS s .1434N PREDICTED NITE RESISTANCE = 67.50 1 RESISTANCE s 24.45 REACTION FOLLOWED ss 74.88 47

ACETAMIDE AT 85 DEGS. RUN 1 TIME RESISTANCE RATE CONSTANT 31-25 68.30 0.2417E-02 45.00 71-50 0.2435E-02 7 3.2 5 77.50 0.2460E-02 91-25 80.80 0 .24 4 7 E-02 106.25 83.40 0.2445E-02 121.75 85.90 0.2440E-02 137-25 88.20 0.2430E-02 151.25 90.60 0.2472E-02 166;50 92.40 0.2439E-02 180.75 94.40 0;2454E-02 196.25 96.30 0-.2452E-02 211.25 98; 00 0.2447E-02 226.75 99; 50 0.2425E-02 240.00 101.10 0.2444E-02 256.75 102.70 0.2435E-02 LEAST SQUARES RATE CONSTANT = 0-.2444E-02 AVERAGE RATE CONSTANT = 0 ; 2443E-02 CORRELATION COEFFICIENT = 0;9998 STANDARD DEVIATION FROM MEAN = 0 . 1358E-0 4 CONCENTRAT ION OF REACTANTS ss .O5 ION PREDICTED INF INITE RESISTANCE ss 165;00 PREDICTED ZERO RESISTANCE ss 60.36 PERCENTAGE OF REACTION FOLLOWED 65.01

'.V •

AT 85 DEGS. RUN 2 TIME RESISTANCE RATE CONSTANT 30.75 67'. 80 0.2443E-02 44; 00 70.90 0.2501E-02 72.2 5 76; 40 0 ;24 7 1E-02 90.50 79:80 0.2495E-02 105.50 8 2; 20 0;2481E-02 121.75 84.60 0-.2464E-02 136.25 86.80 O.2476E-O2 151.25 88.90 0 .2 4 8 2E-02 166.25 90.80 0.2477E-02 181.25 92.60 0.2473E-02 196.25 94.30 0;2469E-02 211.50 96; 00 0 .24 7 2 E-02 227.00 97.60 0.2472E-02 241.25 99.10 0.2482E-02 257.00 100.60 0.2484E-02

LEAST SQUARES RATE CONSTANT =s 0 .24 7 7 E-02 AVERAGE RATE iCONSTANT S 3 0 .2 4 7 6 E-02 CORRELATION COEFFICIENT = 0.9999 STANDARD DEVIATION FROM MEAN ss 0.1285E -04 CONCENTRAT ION OF REACTANTS = .0499N PREDICTED INF INITE RESISTANCE ss 157;20 PREDICTED ZERO RESISTANCE =3 60.31 PERCENTAGE OF REACTION FOLLOWED SS 64.98 * 48

PROPIONAMIDE AT 75 DEGS. RUN 2

TIME RESISTANCE RATE CONSTANT 51.25 65.50 0.1275E -02 104.50 70; 90 0 ;1 298E-02 159;25 75.90 0 ; 1302E-02 226.75 81.40 0.1300E -02 279.50 85; 20 0.1292E-02 340.00 8 9 ;6 o 0.1309E -02 402.50 93; 20 0 ;1 293E-02 466.00 97.00 0 ; 1302E-02 633.75 105.10 O.I 296E-0 2 705.50 108.20 0 . 1300E-02 7 78.25 110.80 0.1289E-02

LEAST SQUARES RATE CONSTANT 25 0 ;1 297E-02 AVERAGE RATE CONSTANT s 0.1296E-02 CORRELATION COEFFICIENT s s 0.9999 STANDARD DEVIATION FROM MEAN s 0.8379E-05 CONCENTRATION OF REACTANTS S3 .0381N PREDICTED INF INITE RESISTANCE SS 178;25 PREDICTED ZERO RESISTANCE SS 59.97 PERCENTAGE OF REACTION FOLLOWED = 69.14

j . A A

PROPIONAMIDE AT 75 DEGS. RUN 3

TIME RESISTANCE RATE CONSTANT 60;75 65.20 0-.1320E-02 123;00 71.00 0; 1304E-02 181 ; 7 5 76.20 0.1321E-02 243.50 80; 90 0 ; 1314E-02 298-.00 84; 80 0 ; I 317 E—0 2 346.75 88; 10 0.1323E-02 393.00 90.80 0 ;1 3 16E-02 437.50 93; 40 0; 1318 E—0 2 481.75 95.80 0 .1 3 1 9E-02 545.50 98.80 0 . 1308E-02

LEAST SQUARES RATE CONSTANT SS 0.1316E -02 AVERAGE RATE 'CONSTANT s s 0.1316E -02 CORRELATION COEFFICIENT s s 0.9999 STANDARD DEVIATION FROM MEAN s s 0.5779E -05 CONCENTRATION OF REACTANTS s s .037 5N PREDICTED INF INITE RESISTANCE = 175.00 PREDICTED ZERO RESISTANCE s s 58.71 PERCENTAGE OF REACTION FOLLOWED = 61.06 Ve ve PROPIONAMIDE AT 85 DEGS. RUN 2

TIME RESISTANCE RATE CONSTANT 4 3.7 5 57:30 0.2542E -02 7 0 .7 5 61.80 0.2554E -02 99.50 66:00 0.2541E -02 126.25 69.70 0.2560E -02 162.25 74.00 0.2554E -02 192:25 77.20 0.2548E -02 221.00 80.20 0-.2569E-02 248.50 82.70 0.2569E -02 278.00 85.10 0.2560E -02 308.25 87:60 0.2579E -02 338.75 89.70 0.2571E -02 373.25 91.80 0.2553E-02 400.00 93:30 0.2540E-02 450.00 96.00 0.253 IE-02

LEAST SQUARES RATE CONSTANT = 0-.2556E-02 AVERAGE RATE CONSTANT = 0.2555E-02 CORRELATION COEFFICIENT = 0.9997 STANDARD DEVIATION FROM MEAN = 0.1343E-04 CONCENTRATION OF REACTANTS = .0437N PREDICTED INFINITE RESISTANCE = 11*3:55 PREDICTED ZERO RESISTANCE = 48.97 PERCENTAGE OF REACTION FOLLOWED = 74.35 *

PROPIONAMIDE AT 85 DEGS. RUN 3

TIME RESISTANCE RATE CONSTANT 52.00 87:40 0 : 2572E-0 2 87:25 95.10 0 . 2536E-0 2 119.75 101:70 0.2557E -02 150.50 106.90 0.2530E -02 180:00 111:70 O.2536E-O2 210.00 116.20 0.2546E -02 239.00 120.40 0 ; 2572E-02 283.50 125.60 O.2556E-O2 303.00 128.00 0.2575E -02 329.50 130.70 0.2570E -02 366.75 134:00 0;2548E-02 415:50 138.20 0.2545E -02 4 7 2 .OO 142.40 0.2534E -02

LEAST SQUARES RATE CONSTANT = 0.2552E-02 AVERAGE RATE CONSTANT = 0:2552E-02 CORRELATION COEFFICIENT = 0:9997 STANDARD DEVIATION FROM MEAN = 0.1550E-04 CONCENTRATION OF REACTANTS = .0 4 1 9N PREDICTED INF INITE RESISTANCE = 210.00 PREDICTED ZERO RESISTANCE = 73.41 PERCENTAGE OF REACTION FOLLOWED = 74.49 50

PROP 1ONAMIDE AT 95 DEGS. RUN 1 TIME RESISTANCE RATE CONSTANT 23.50 50:20 0 :4 3 24E-02 43:25 54:70 0.4139E-02 71.00 60.80 0:4250E-02 94.00 64:80 0.4214E-02 109.25 67:60 0.4305E-02 131.50 70.80 0-.4295E-02 149.75 73:00 0 .4251E-02 172.25 75.70 0 .4261E-02 190.75 77.60 0 .4243E-02 210:25 79:50 0.4239E-02 231.25 81.30 0.4220E-02 LEAST SQUARES RATE CONSTANT = 0.4249E-02 AVERAGE RATE CONSTANT = 0.4249E-02 CORRELAT ION COEFFICIENT “ 0:9996 STANDARD DEVIATION FROM MEAN = 0.4790E-04 CONCENTRATION OF REACTANTS = .0456N PREDICTED INFINITE RESISTANCE = 123;25 PREDICTED ZERO RESISTANCE = 43.31 PERCENTAGE OF REACTION FOLLOWED = 72.04

PROP IONAMI DE AT 95 DEGS. RUN 2

TIME RESISTANCE RATE CONSTANT 2 2; 7 5 48.70 0:4673E-02 42.75 53'. 30 0:4433E-02 70.25 59'. 30 0.4517E-02 93 : 50 63:50 0.4526E-02 109.25 66:10 0:4551E-02 130.75 69:30 0.4580E-02 148.75 71:60 0.4573E-02 172.00 74.20 0.4549E-02 190.00 76:00 0:4529E-02 209.25 77:90 0:4541E-02 230.25 79.70 0 .45 3 1 E-02 LEAST SQUARES RATE CONSTANT = 0:4543E-02 AVERAGE RATE CONSTANT = 0.4546E-02 CORRELATION COEFFICIENT = 0.9997 STANDARD DEVIATION FROM MEAN = 0.5437E -04 CONCENTRATION OF REACTANTS = .0454N PREDICTED INFINITE RESISTANCE = 119.07 PREDICTED ZERO RESISTANCE = 41.80 PERCENTAGE OF REACTION FOLLOWED = 73.28 * * 51

BUTYRAMIDE AT 75 DEGS. RUN 1

TIME RESISTANCE RATE CONSTANT 164;00 97; 60 0.7166E-03 230.75 102.50 0 . 7 132E-03 322.25 108.60 0.7059E-03 393.25 113.10 0.7052E-03 471.75 117.90 0.7080E-03 639.75 127.10 0 .7 101E-03 710.75 130.90 0.7162E-03 783.50 134.00 0:7099E-03 1435.75 158.30 0.7162E-03 1548.50 161.10 0.7090E-03 1677.00 164.40 0.7068E-03 LEAST SQUARES RATE CONSTANT = 0.7105E-03 AVERAGE RATE CONSTANT = 0.7106E-03 CORRELATION COEFFICIENT = 0.9999 STANDARD DEVIATION FROM MEAN = 0.4051E-05 CONCENTRATION OF REACTANTS = .0382N PREDICTED INFINITE RESISTANCE = 257:55 PREDICTED ZERO RESISTANCE = 83.89 PERCENTAGE OF REACTION FOLLOWED = 72.63

-k * *

BUTYRAMIDE AT 75 DEGS. RUN 2

TIME RESISTANCE RATE CONSTANT 163; 50 94; 10 0-.6973E-03 230:00 98; 60 0.6896E-03 321.50 104.50 0.6885E-03 392;25 108;80 0.6894E-03 471;00 113.30 0.6903E-03 639;00 122.30 0:6984E-03 710.00 125:70 0.6995E-03 782.75 129:00 0.7006E-03 1437.25 151.70 0.6957E-03 1547.75 154.50 0.6918E-03 1676.25 157.60 0.6886E-03 LEAST SQUARES RATE CONSTANT = 0-.6937E-03 AVERAGE RATE CONSTANT = O.6936E-O3 CORRELATION COEFFICIENT = 0.9998 STANDARD DEVIATION FROM MEAN = 0.4510E-05 CONCENTRATION OF REACTANTS = .0381N PREDICTED INFINITE RESISTANCE = 248:00 PREDICTED ZERO RESISTANCE = 81.26 PERCENTAGE OF REACTION FOLLOWED = 72.04 * 52

BUTYRAMIDE AT 85 DEGS. RUN 1 TIME RESISTANCE RATE CONSTANT 4 8.2 5 76; 40 0.1218E -02 104.50 83; 10 0.1183E-02 175.75 90.80 0.1177E -02 234.25 96.90 0.1198E-02 292.25 102.20 0; 1202E-02 352.25 107.20 0 ;1 204E-02 413.25 112.00 0 .1 2 1 2E-02 469.00 115.60 0.120 IE-02 530.50 119.60 0.1203E -02 592.00 123.00 0 ;1 194E-02 644;50 125.90 0 .1 1 95E-02 6 95.25 128.30 0 .1 187E-0 2

LEAST SQUARES RATE CONSTANT = 0 ;1 1 98E-02 AVERAGE RATE CONSTANT = 0 ;1 1 98E-02 CORRELATION COEFFICIENT s 0-.9998 STANDARD DEVIATION FROM MEAN S 3 0 .1 102E-04 CONCENTRATION OF REACTANTS ss .0435N PREDICTED INF INITE RESISTANCE ss 214;50 PREDICTED ZERO RESISTANCE = S 69.72 PERCENTAGE OF REACTION FOLLOWED 67.65

JU

AT 85 DEGS. RUN 2

TIME RESISTANCE RATE CONSTANT 46; 50 77'. 20 0 ;1 260E-02 103;50 84; 00 0.1198E-02 174;00 91'.90 0 ; 1201E-02 232;50 98; 10 0 ;1 221E-02 290;00 103'.30 0". 1217E-02 351:00 108.80 0 .1 235E-02 411.25 112;90 0 ;1 214E-02 467.00 117.10 0 .1 226E-02 529.00 121.20 0 . 1229E-0 2 590.00 124;50 0 ;1 217E-02 642.75 127.50 0 .1 2 1 9E-02 693.75 129.90 0.121 IE-02

LEAST SQUARES RATE CONSTANT SS O'. 1 219E-02 AVERAGE RATE CONSTANT S 3 0.1221E-02 CORRELATION COEFFICIENT SS 0.9997 STANDARD DEVIATION FROM MEAN S3 0 . 1569E-0 4 CONCENTRATION OF REACTANTS SS .0437N PREDICTED INF INITE RESISTANCE =5 214.50 PREDICTED ZERO RESISTANCE SS 70.47 PERCENTAGE OF REACTION FOLLOWED = 68.13

A * * 53

AT 95 DEGS. RUN 2 TIME RESISTANCE RATE CONSTANT 3 5.5 0 66:60 0 ;2282E-02 6 4 .7 5 72:00 0.2234E-02 9 8 .7 5 77.40 0.2183E-02 124.25 81:70 0.2238E-02 154.00 85:80 0.2230E-02 184.75 8 9.9 0 0.2247E-02 215.25 93.20 0 ;2222E-02 243.00 96.60 O'. 2260E-02 279.25 100.20 0.2261E-02 3 07 .2 5 102.60 0.2249E-02 333.25 104:60 0;2232E-02 364:50 107.00 0.2226E-02 395.00 109.20 0 .2222E-02 LEAST SQUARES RATE CONSTANT = 0-.2236E-02 AVERAGE RATE CONSTANT = 0-.2237E-02 CORRELATION COEFFICIENT = 0.9996 STANDARD DEVIATION FROM MEAN = 0.2303E-04 CONCENTRATI ON OF REACTANTS = .0458N PREDICTED 1NFIN ITE RESISTANCE = 172;70 PREDICTED ZERO RESISTANCE = 58.83 PERCENTAGE OF REACTION FOLLOWED = 69.95 Ve Ve

AT 95 DEGS. RUN 1

TIME RESISTANCE RATE CONSTANT 37:00 70:70 0.2347E-02 66.75 76:40 0.2199E-02 9 9.7 5 82:60 0.2199E-02 126:50 87:40 0.2227E-02 156:00 92:00 0.2226E-02 186:75 96:60 0.2245E-02 216.50 100.80 0.227 IE-02 244.75 104.20 0.2270E-02 281:00 108.20 0.2270E-02 309.50 110.80 0.22A8E-02 335:00 113.10 0.22^0E-02 366.25 115:80 0.2236E-02 396.75 118.20 0.2228E-02 LEAST SQUARES RATE CONSTANT = 0'.22M+E-02 AVERAGE RATE CONSTANT = 0.2247E-02 CORRELATION COEFFICIENT = 0.999^ STANDARD DEVIATION FROM MEAN = 0.3688E-04 CONCENTRATION OF REACTANTS = .0A86N PREDICTED INFINITE RESISTANCE = 188; 40 PREDICTED ZERO RESISTANCE = 61.33 PERCENTAGE OF REACTION FOLLOWED = 71.33

A * 54

AT 75 DEGS. 1RUN 1 TIME RESISTANCE RATE CONSTANT 31.25 70:50 0.5804E-03 90.75 74:70 0:54958-03 150.50 79.00 0.5596E-03 215.00 82.90 0.5450E-03 269.75 86.30 0.5464E-03 330.25 90.10 0.5540E-03 394.00 93.70 0.5546E-03 450.25 96.70 0.5545E-03 511.00 99.70 0.5524E-03 570.25 102:80 0.5571E-03 631.00 105:40 0.5527E-03 690.25 108:10 0.5541E-03 750.50 110.70 0.5549E-03 811.50 113.20 0-.5552E-03 867.50 115:30 0-.5538E-03 1032.75 121.10 0.5510E-03 LEAST SQUARES RATE CONSTANT s 0-.5535E-03 AVERAGE RATE CONSTANT r= 0-.5547E-03 CORRELATION COEFFICIENT = 0:9999 STANDARD DEVIATION FROM MEAN = 0.7529E-05 CONCENTRATION OF REACTANTS s .0507N PREDICTED INF INITE RESISTANCE as 226:25 PREDICTED ZERO RESISTANCE =S 67.99 PERCENTAGE OF REACTION FOLLOWED 62.70

AT 75 DEGS. RUN 2 TIME RESISTANCE RATE CONSTANT 30:25 69:70 0.5853E-03 90:00 73:80 0.5415E-03 149:25 77:90 0-.5460E-03 213:25 82.00 0.5445E-03 268.25 85:40 0.5456E-03 328.75 89:00 0-.5476E-03 393.25 92:60 0.5480E-03 449.50 95.60 0.5486E-03 509.50 98.50 0.5457E-03 568.25 101:60 0.5513E-03 629.00 104.30 0.5491E-03 688.50 107.00 0.5505E-03 748.75 109.50 0.5496E-03 810.25 112.00 O-.5498E-O3 866:75 114.10 0.5482E-03 1033.25 119.90 0.5452E-03 LEAST SQUARES RATE CONSTANT 0.5483E-03 AVERAGE RATE CONSTANT =s O.5498E-O3 CORRELATION COEFFICIENT = 0.9999 STANDARD DEVIATION FROM MEAN sa O.9493E-05 CONCENTRATION OF REACTANTS =3 . 0509N PREDICTED INF INITE RESISTANCE =s 225:63 PREDICTED ZERO RESISTANCE = 67.26 PERCENTAGE OF REACTION FOLLOWED =5 62.55 55

VALERAMI DE AT 85 DEGS. RUN1

TIME RESISTANCE RATE CONSTANT 55.50 65.30 0 . 1120E-02 117.00 7 1.7 0 0.1083E -02 176.00 77.30 0.1077E -02 239.50 82.80 0.1078E -02 296.75 8 7.5 0 o-. 1089E-0 2 356.50 91.80 0 . 1089E-0 2 4 01.75 94.80 0.1089E -02 451.50 98.00 0.1094E -02 473'.75 99.40 0 ; IO97E-0 2 506.50 101.20 0.1095E -02 546.50 103.30 0.1093E -02 594.25 105.70 0 .10 9 1 E-02 652.50 108.40 O.IO 89E-O2 706.50 110.60 O.IO 8 IE -02

LEAST SQUARES RATE CONSTANT = 0'.1090E-02 AVERAGE RATE CONSTANT = O .IO 9OE-O2 CORRELATION COEFFICIENT = 0.9998 STANDARD DEVIATION FROM MEAN = 0.1016E-04 CONCENTRATION OF REACTANTS = .O507N PREDICTED INF INITE RESISTANCE = 183.15 PREDICTED ZERO RESISTANCE = 58.40 PERCENTAGE OF REACTION FOLLOWED =69.29 /\ /\ ^S\ " - ■ ■ ■ ...

VALERAM1 DE AT 85 DEGS. RUN 2 TIME RESISTANCE RATE CONSTANT 52.25 68.10 O'. 1133E-02 114.00 74.60 0.1062E-02 173.00 80.90 0.1086E -02 236.25 86.60 0 .10 8 1 E-02 294'. 00 91.60 O.IO 9 IE -02 352.50 96; 00 0 . 1088E-0 2 3 98'.25 99.20 0; 1088E-0 2 448.25 102.60 0 .1 0 9 3 E-02 470.00 104.10 0 . 1098E-0 2 503.25 105.90 0 . 109IE-0 2 543.25 108.30 0.1095E -02 590.75 110.90 0.1097E -02 649.00 113.50 0.1085E -02 7 02.75 115.90 O.IO 8 IE -02 S RATE CONSTANT = O.IO 9OE-O2 CONSTANT = 0 .1 0 9 1 E-02 COEFFICIENT = 0.9997 1AT ION FROM MEAN = 0.1467E -04 CONCENTRATION OF REACTANTS = .0508N PREDICTED INFINITE RESISTANCE = 192.56 PREDICTED ZERO RESISTANCE = 61.17 PERCENTAGE OF REACTION FOLLOWED = 69.21

yv 56

AT 95 DEGS. RUN 1

TIME RESISTANCE RATE CONSTANT 3 4.7 5 63'.40 0.1865E-02 6 7.2 5 69.00 0.1839E-02 9 4.7 5 73.40 0:1841E—02 121.25 77.30 0 .18 4 1 E—02 156.00 82.00 0.1843E-02 180.25 85.10 0.1850E-02 212.50 89.00 0.1863E-02 244.50 92.30 0.1854E-02 273.00 95.20 0 : 1860E-02 301.75 97 '.80 0.1855E-02 333.50 100.60 0.1859E-02 361.00 102.60 0 : 1844E-02 390.25 104.60 0.1830E-02 LEAST SQUARES RATE CONSTANT s 0.1849E-02 AVERAGE RATE CONSTANT a 0 : 1850E-02 CORRELATION COEFFICIENT s 0:9998 STANDARD DEVIATION FROM MEAN a 0.1023E-04 CONCENTRATION OF REACTANTS — .0507N PREDICTED INF INITE RESISTANCE a 176.00 PREDICTED ZERO RESISTANCE a 56.52 PERCENTAGE OF REACTION FOLLOWED 67.71 /V /V *“V

AT 95 DEGS. RUN 2

TIME RESISTANCE RATE CONSTANT 3 5; 00 63.40 0 : 1746E-02 67.50 69.50 0.1845E-02 95'. 50 73.40 O.I7 7 OE-0 2 121.50 77.20 0.1776E-02 155-75 81:80 0.1780E-02 180.50 84.80 0: 1777E-02 212.50 88:60 0 . 1788E-0 2 244.00 92.00 0 : 1793E-02 273.50 94:80 0 . 1786E-0 2 301.50 97.60 0: 1802E-02 332.25 100.20 0.1798E-02 360.25 102.20 0.1781E-02 390.00 104.30 0 . 1771E-0 2

LEAST SQUARES RATE CONSTANT £3 0-.1786E-02 AVERAGE RATE CONSTANT = 0 : 1786E-0 2 CORRELATION COEFFICIENT a 0:9997 STANDARD DEV LAT ION FROM MEAN a 0.2202E -04 CONCENTRATION OF REACTANTS = .0509N PREDICTED INF INITE RESISTANCE = 176.80 PREDICTED ZERO RESISTANCE = 56.83 PERCENTAGE OF REACTION FOLLOWED = 67.07 * 57

SO-VALERAMIDE AT 75 DEGS. RUN 1

TIME RESISTANCE RATE CONSTANT 74.50 77.80 0.21378-03 347.25 82.80 0.1743E-03 722.00 90.80 0.1941E-03 1438.50 102.60 0.1952E-03 1782.50 107.10 o . 1927E-0 3 2147.25 111.80 O.I 936E-O3 2872.75 119.70 0 ;1933 E—03 3220.25 122.90 0.1924E-03 3580.50 126.00 O.I 919E-O3 4318.50 132.70 O.I 976E-O3 4701.00 134.20 0.1904E-03 5003.00 136.10 0; 1 9OOE-O3 5747.50 140.60 O.I 905E-O3

LEAST SQUARES RATE CONSTANT =5 O.I923E-O3 AVERAGE RATE CONSTANT SS O-.I9 3IE-O3 CORRELATION COEFFICIENT SS 0.9993 STANDARD DEVIATION FROM MEAN SS 0.7984E-05 CONCENTRATION OF REACTANTS SS .0432N PREDICTED INFINITE RESISTANCE S3 203;00 PREDICTED ZERO RESISTANCE S 75.91 PERCENTAGE OF REACTION FOLLOWED 73.49

iV iV* '

SO-VALERAMIDE AT 75 DEGS. RUN 2

TIME RESISTANCE RATE CONSTANT 74.25 79.30 O.25O5E-O3 347.25 84.70 O.I927E-O3 721.75 92.00 0 ; I 935E-O3 1438.00 104.40 0 ; 2000E-03 1782.00 109.40 0.201 IE-03 2146.75 114.60 O.205OE-O3 2872.50 122.30 O.202IE-O 3 3219.75 125.40 0.2003E-03 3580.25 128;90 0 ; 2022E-03 4320.25 134.40 O.2OOOE-O3 4701;25 137-10 0 ; 2002E-03 5003.50 139.20 O.2OIOE-O3 5747.25 143.60 O.20IOE-O3

LEAST SQUARES RATE CONSTANT ss O.20IOE-O3 AVERAGE RATE ICONSTANT ss O.2038E-O3 CORRELATION COEFFICIENT = 0-.9997 STANDARD DEVIATION FROM MEAN ss 0 . 1386E-0A CONCENTRATION OF REACTANTS ss .0431N PREDICTED INF 1NITE RESISTANCE ss 20A;00 PREDICTED ZERO RESISTANCE ss 77.09 PERCENTAGE OF REACTION FOLLOWED S3 lb.k5 * * 58

ISO-VALERAMIDE AT 85 DEGS. RUN 1

TIME RESISTANCE RATE CONSTANT 41:50 53:40 0 :3831E-03 221.75 58:10 0.3972E-03 465.00 63.50 0.3950E-03 579.50 65.60 0-.3886E-03 731:25 69:20 0.4145E-03 1429.50 79:00 0.3996E-03 1547:00 80.40 0:3997E-03 1671:25 81.80 0.3997E-03 1806.00 83.00 0 .39 4 8 E-03 1895.75 83:90 0:3948E-03 2013.50 85.00 0.3941E-03 2135.50 86.30 0.3979E-03 2867.50 92.10 0.4004E-03

LEAST SQUARES RATE CONSTANT — 0.3980E-03 AVERAGE RATE CONSTANT ss 0-.3969E-03 CORRELATION COEFFICIENT ss 0:9996 STANDARD DEVIATION FROM MEAN = 0.6938E-05 CONCENTRAT ION OF REACTANTS ss .0393N PREDICTED INF 1N ITE RESISTANCE ss 129:68 PREDICTED ZERO RESISTANCE ss 52.28 PERCENTAGE OF REACTION FOLLOWED 72.44 'V

■VALERAMIDE AT 85 DEGS. RUN 2

TIME RESISTANCE RATE CONSTANT 43:00 52:50 0:4963E-03 223:50 56:60 0.3875E-03 466:25 62:20 0:4060E-03 580:25 64:30 0:4008E-03 732.25 67:20 0.4062E-03 1431:25 77.40 0.4102E-03 1548.25 78:70 0.4089E-03 1672:50 80.10 0:4098E-03 1807.50 81:50 0-.4100E-03 1897:75 82:30 0:4080E-0 3 2015.25 83.30 0 .40 5 8 E-03 2137.00 84:30 0.4040E-03 2868.75 89.90 0.4062E-03 LEAST SQUARES RATE CONSTANT ss 0.4072E-03 AVERAGE RATE 1CONSTANT ss 0 :4123E-03 CORRELATION COEFFICIENT Ä 0.9997 STANDARD DEVIATION FROM MEAN ss 0.2493E -04 CONCENTRAT ION OF REACTANTS ta .0391N PREDICTED INF IN ITE RESISTANCE ss 126:04 PREDICTED ZERO RESISTANCE ss 51.05 PERCENTAGE OF REACTION FOLLOWED ss 72.63 * * 59

ISO-VALERAMIDE AT 95 DEGS. RUN 1

TIME RESISTANCE RATE CONSTANT 47.00 72.70 0;8746E-03 144.50 78.60 0.8034E-03 227.00 83; 20 0.8023E-03 320.00 88.00 0;8109E-03 404.00 91 ; 90 0;8l66E-03 468.75 94.50 0-.8133E-03 530;50 97.00 0.8186E-03 585.75 99.10 0.8229E-03 656.75 101.50 0;8229E-03 707'. 25 10 2; 90 0;8153E-03 1443.00 119.60 0-.8198E-03 1493.50 120.20 0.8124E-03 LEAST SQUARES RATE CONSTANT = 0.8166E-03 AVERAGE RATE CONSTANT = 0;8194E-03 CORRELATION COEFFICIENT = 0;9998 STANDARD DEVIATION FROM MEAN = 0.1781E-04 CONCENTRATION OF REACTANTS = .0392N PREDICTED INFINITE RESISTANCE = 164;38 PREDICTED ZERO RESISTANCE = 69.11 PERCENTAGE OF REACTION FOLLOWED = 73.34

A *

ISO-VALERAMIDE AT 95 DEGS. RUN 2

TIME RESISTANCE RATE CONSTANT 45.75 73'. 20 0.8381E-03 143;25 79'.30 0;7944E-03 225'. 50 84; 10 0-.8018E-03 319.00 8 9; 00 0.8074E-03 402.75 92.90 0;8087E-03 468;00 95; 60 0-.8059E-03 529.00 98.30 0.8177E-03 584.25 100;50 0.823 IE-03 655.00 102.70 0.8130E-03 706.50 104.40 0.8136E-03 1441.25 121.40 0.8081E-03 1491.75 122.20 0.8064E-03 LEAST SQUARES RATE CONSTANT 0;8l06E-03 AVERAGE RATE CONSTANT 0.8115E-03 CORRELATION COEFFICIENT 0.9998 STANDARD DEVIATION FROM MEAN 0.1067E-04 CONCENTRATION OF REACTANTS .0391N PREDICTED INFINITE RESISTANCE 168.75 PREDICTED ZERO RESISTANCE 69.77 PERCENTAGE OF REACTION FOLLOWED 73.15

* X 60

PHENYLACETAMIDE AT 75 DEGS. RUN 1

TIME RESISTANCE RATE CONSTANT 33.00 68.20 0.1796E-02 61.00 70.20 0 . 1800E-02 93.00 7 2.30 0.1798E-02 123.00 74.20 0 .1 8 1 5E-02 152.00 75.80 0.1803E-02 183.50 77.60 0.1828E-02 216.25 79.10 0.1805E-02 250.00 80.70 0.1813 E—0 2 278.50 81.90 0.1808E-02 304.25 82.90 0 ; 1800E-02 333.50 84.00 0.1796E-02 365.75 85.20 0 . 1800E-02 401.75 86.60 0 ; 1823E-02 428.25 87.30 0 . 1802E-02 LEAST SQUARES RATE CONSTANT s 0;1807E-02 AVERAGE RATE CONSTANT = 0 ; 1806E-02 CORRELATION COEFFICIENT = 0.9999 STANDARD DEVLAT ION FROM MEAN = 0.9618E-05 CONCENTRATION OF REACTANTS s .0250N PREDICTED 1NF 1 NITE RESISTANCE a 123.25 PREDICTED ZERO RESISTANCE = 65.65 PERCENTAGE OF REACTION FOLLOWED = 53.06

PHENYLACETAMIDE AT 75 DEGS. RUN2

TIME RESISTANCE RATE CONSTANT 32.50 66.30 0.1678E-02 60.00 68-.40 0 .17 1 9E—02 92.50 70.80 0.1763E-02 122.00 72.50 0.1710E-02 151.00 74.20 0.1703E-02 183.75 76.10 0 .1 7 1 5E-02 215.25 77.80 0.1723E-02 249.25 79.40 0.1713E—02 277.75 80.70 0.1711E-0 2 303.75 81.90 0.1719E-0 2 333.00 83.10 0.1717 E—02 365.00 84.30 0.1710E-02 401.00 85.80 0.1730E-02 427.75 86.60 O.I7 I4E—02 LEAST SQUARES RATE CONSTANT 0.1717 E-02 AVERAGE RATE CONSTANT 0.1716E-02 CORRELATION COEFFICIENT 0.9999 STANDARD DEVIATION FROM MEAN 0.1726E-04 CONCENTRATION OF REACTANTS .0260N PREDICTED INFINITE RESISTANCE 127.50 PREDICTED ZERO RESISTANCE 63.76 PERCENTAGE OF REACTION FOLLOWED* 52.76 * 61

PHENYLACETAMIDE AT 85 DEGS # RUN 1

TIME RESISTANCE RATE CONSTANT 30.50 65.20 0.2888E -02 62.50 68 ; 60 0 . 2887E-0 2 90.00 71.30 0.2918E -02 132.25 74.80 0 . 2897E-0 2 172.25 77.90 O.2937 E-0 2 215.25 80.60 0.2917E -02 250.25 82.50 0 . 2891E-0 2 292.50 84.70 O'. 2895E-0 2 3 29.25 86.40 0.2892E -02 36 1.0 0 8 7 .90 O.292OE-O2 390.50 8 9 .IO 0.2925E -02 421.75 90.00 O.2876E-O2 450.25 91.20 0.2917E-02

LEAST SQUARES RATE CONSTANT — 0'.2906E-02 AVERAGE RATE 'CONSTANT = O.2905E-O2 CORRELATION COEFFICIENT 3 0.9998 STANDARD DEVIATION FROM MEAN 3 0.1771E -04 CONCENTRAT ION OF REACTANTS 3 .0250N PREDICTED INF IN ITE RESISTANCE 3 121.95 PREDICTED ZERO RESISTANCE 3 61.53 PERCENTAGE OF REACTION FOLLOWED 3 65.67

PHENYLACETAMIDE AT 85 DEGS. RUN 2

TIME RESISTANCE RATE CONSTANT 30.00 65.40 0.2983E-02 61.50 69.40 0.3145E -02 89'. 7 5 72.30 0.3106E-02 132.25 76.00 0.3044E-02 171.50 79'.30 0.3092E-02 214.50 82.20 0.3072E-02 249.75 84.40 0.3080E-02 292.00 8 6 .70 0.3076E-02 328.50 88.60 O.3097E-O2 360.00 90.00 0 .3 0 9 3 E-02 390.50 91.30 0.3100E-02 420.50 92.30 0.3068E-02 449.25 93.30 O.3O6 IE-0 2 LEAST SQUARES RATE CONSTANT = 0.3081E-02 AVERAGE RATE CONSTANT = 0.3078E -02 CORRELATION COEFFICIENT = 0.9998 STANDARD DEVIATION FROM MEAN = O.3 6 3 IE -0 4 CONCENTRATION OF REACTANTS = .0260N PREDICTED INFINITE RESISTANCE = 1 24.20 PREDICTED ZERO RESISTANCE = 61.46 PERCENTAGE OF REACTION FOLLOWED = 67.56 * * 62

PHENYLACETAMIDE AT 95 OEGS. RUN 1

TIME RESISTANCE RATE CONSTANT 29.25 63.10 0.4564E -02 4 9.2 5 66.40 0 .4 7 4 7 E-02 7 6 .2 5 69.80 0.4616E -02 101.00 72.90 0.471 IE-02 120.00 74.80 0 .4 6 7 3 E-02 141.00 76.80 0.4674E -02 161.50 78.40 0 ;4 6 l4 E -0 2 181.75 80.10 0 .46 4 8 E-02 201.00 81.40 0 .4 6 1 5E -02 227.50 83 '.50 0.4726E -02 242.50 84.20 0 .4 6 54E-02 282.00 86.40 0.4655E-02

LEAST SQUARES RATE CONSTANT = 0.4660E-02 AVERAGE RATE CONSTANT = 0;4658E-02 CORRELATION COEFFICIENT = 0.9996 STANDARD DEVI AT ION FROM MEAN = 0.5026E-04 CONCENTRATION OF REACTANTS = .0250N PREDICTED INFINITE RESISTANCE = 116.45 PREDICTED ZERO RESISTANCE = 57.97 PERCENTAGE OF REACTION FOLLOWED = 65.53

* jlr\

PHENYLACETAMIDE AT 95 DEGS. RUN 2

TIME RESISTANCE RATE CONSTANT 28; 25 62.00 0;4627E-02 48.50 65.40 0 .46 9 1 E-02 7 4 .2 5 69'. 20 0.473 IE-02 99.25 72; 10 0.4627E-02 118.00 74; 00 0.4555E -02 139.00 76.70 0.4755E-02 161.00 78.80 0.4772E -02 181.25 80.60 0 .47 9 8 E-02 198.7 5 81.80 0.4743E-02 225.50 83.50 0 .46 7 7 E-02 240.25 84.50 0 .4 6 8 5 E-02 280.50 86.60 0.4595E -02 LEAST SQUARES RATE CONSTANT = 0 .4 6 9 1 E-02 AVERAGE RATE CONSTANT = 0 ;4688E-02 CORRELATION COEFFICIENT = 0.9986 STANDARD DEVIATION FROM MEAN =» 0.7196E -04 CONCENTRATION OF REACTANTS = .0260N PREDICTED INFINITE RESISTANCE = 119-00 PREDICTED ZERO RESISTANCE = 56.66 PERCENTAGE OF REACTION FOLLOWED = 66.00 'k :k * CYCLOHEXYLACETAMIDE AT 75 DEGS. RUN 1

TIME RESISTANCE RATE CONSTANT 7 2 .7 5 59.20 O.I78 6 E-O3 189.25 60 ;90 0.1770E-03 407.25 63.90 0; 1756E-03 660.50 67:60 0.1845E-03 1402.75 75.60 O.I75 6 E-0 3 1549.75 77.40 0 . 1793E-03 1715.50 78.90 0 . 1779E-03 1833.00 80.30 0.1809E-03 2882.25 8 8 ;60 0 .17 7 1 E-0 3 2986.50 89.60 0 ; 1792E-03 3121.25 90; 60 0 ; 1795E-03 3274.50 91:70 0 ; 1799E-03 3498;75 93.10 0 ; 1792E-03 4247.75 97.50 0.1784E-03

LEAST SQUARES RATE CONSTANT « 5 O.I789E-O3 AVERAGE RATE CONSTANT = 0 ; 1788E-03 CORRELATION COEFFICIENT = 0-.9998 STANDARD DEVIATION FROM MEAN s s 0.2185E-05 CONCENTRATION OF REACTANTS S3 .0402N PREDICTED INFINITE RESISTANCE = 157:29 PREDICTED ZERO' RESISTANCE ss 58.09 PERCENTAGE OF REACTION FOLLOWED 64.09

*. JU ..u

CYCLOHEXYLACETAMIDE AT 75; DEGS. RUN 2

TIME RESISTANCE RATE CONSTANT 406.25 61; 90 0 . 1691E-0 3 659:75 65; 40 O.I7 8 IE-O 3 1401.75 73; 50 0.1764E-03 1549:50 74.80 0;1747E-03 1715:50 76.30 0;1741E-03 1832.25 77:60 0 .17 6 7 E-03 2881.50 85:50 O.I7 2 7 E-O3 2986.50 8 6; 60 0.1758E-03 3120.25 87.40 0-.1749E-03 3274.50 88.60 0; 1764E-03 3498.50 90.00 0.1762E-03 4247.25 94.00 0.1737E-03 LEAST SQUARES RATE CONSTANT = 0;17 51E-03 AVERAGE RATE CONSTANT s s 0.1749E-03 CORRELATION COEFFICIENT = 0.9996 STANDARD DEVIATION FROM MEAN s s 0.2273E -05 CONCENTRATION OF REACTANTS = .0403N PREDICTED INFI NITE RESISTANCE S3 152.00 PREDICTED ZERO RESISTANCE S3 56.47 PERCENTAGE OF REACTION FOLLOWED = 63.53 6 4

CYCLOHEXYLACETAMIDE AT 85 DEGS. RUN 1

TIME RESISTANCE RATE CONSTANT 65:75 77.20 0 :4 1 23E-03 172.50 81.10 0.3930E-03 271.00 84:20 0.3777E-03 3 92 .7 5 88:30 0.3855E-03 497:00 91.80 0.3958E-03 577:75 93:80 0.3879E-03 651:25 95.90 0:3903E-03 1360:50 111.70 0.3934E-03 1449:50 113.10 0.3904E-03 1540:75 114:60 0-.3896E-03 1631.50 116:20 0.3913E-03 1738:25 117:70 O.3889E-O3 1808.75 118.70 0.3880E-03

LEAST SQUARES RATE CONSTANT =3 0.3900E-03 AVERAGE RATE CONSTANT S 0 :3911E-03 CORRELATION COEFFICIENT = 0:9999 STANDARD DEVIATION FROM MEAN S 0.7444E -05 CONCENTRATION OF REACTANTS s= .0402N PREDICTED INFI NITE RESISTANCE s 186:00 PREDICTED ZERO RESISTANCE =s 74.44 PERCENTAGE OF REACTION FOLLOWED 62.17 JL. />

CYCLOHEXYLACETAM IDE AT 85 DEGS. RUN 2

TIME RESISTA RATE CONSTANT 64:25 75.30 0.4270E-03 170:50 79.10 0:4009E-03 274.25 82:30 0.3838E-03 391:00 86:30 0.3963E-03 495.50 89:40 0-.3966E-03 576:00 91.70 0.3979E-03 6 49.25 93:70 0-.3990E-03 1359.00 109:20 o.4o29E-03 1448:50 110:60 0.4004E-03 1539.25 112.10 0.4003E-03 1630.00 113:30 0.3965E-03 1736.50 114:90 0.3964E-03 1806.75 115.80 0.3945E-03 LEAST SQUARES RATE CONSTANT = 0.3980E-03 AVERAGE RATE CONSTANT = 0.3994E-03 CORRELATION COEFFICIENT = 0:9998 STANDARD DEVIATION FROM MEAN = 0.9115E-05 CONCENTRATION OF REACTANTS = .0402N PREDICTED INFINITE RESISTANCE = 180:00 PREDICTED ZERO RESISTANCE = 72.59 PERCENTAGE OF REACTION FOLLOWED = 62.53 65

CYCLOHEXYLACETAMIDE AT 95 DEGS. RUN 1

TIME RESISTANCE RATE CONSTANT 136.25 51; 50 0;6813E-03 188.75 53.60 0.6890E-03 256.75 55.70 0.661 IE-03 3 15.25 57 ; 90 0.6795E-03 3 76.50 59;8o O.6 7 8 OE- 0 3 4 41.25 61.70 0-.6777E-03 494;50 63.20 0-.6789E-03 554.50 64; 90 0.6847E-03 616;00 66.40 0;6 8 3 IE-03 685.50 6 7 ; 80 0-.673 IE-03 739.50 6 9 .1 0 0.6776E-03 LEAST SQUARES RATE CONSTANT SS 0-.6784E-03 AVERAGE RATE CONSTANT ss 0-.6786E-03 CORRELATION COEFFICIENT ss 0.9996 STANDARD DEVIATION FROM MEAN = : 0.6834E-05 CONCENTRATION OF REACTANTS - .0421N PREDICTED INFI NITE RESISTANCE ss 119.35 PREDICTED ZERO RESISTANCE ss 45.63 PERCENTAGE OF REACTION FOLLOWED 54.99 Vc -k ■

CYCLOHEXYLACETAMIDE AT 95 DEGS. RUN 2

TIME RESISTANCE RATE CONSTANT 7 5.5 0 48 ;80 0-.7089E-03 136.00 5 1; 10 0.6800E-03 188;00 53.00 0.6745E-03 256.00 55.30 0.6689E-03 314;50 57'. 50 0.6899E-03 376.25 59; 50 0.6954E-03 441.75 61.20 0.6840E-03 494;00 62.70 0.6884E-03 553;50 64; 20 0.6868E-03 615.25 65; 60 0.6821E-03 684.50 67.20 0.6832E-03 738.50 68.40 0.6848E-03 LEAST SQUARES RATE CONSTANT =s 0.6849E-03 AVERAGE RATE CONSTANT = O.6856E-O3 CORRELATION COEFFICIENT =3 0.9997 STANDARD DEVIATION FROM MEAN = 0.9656E -05 CONCENTRATION OF REACTANTS . PREDICTED INFINITE RESISTANCE = 116.20 PREDICTED ZERO RESISTANCE = 45.36 PERCENTAGE OF REACTION FOLLOWED = 55.25 METHOXYACETAMI DE AT 35 DEGS. RUN 1

TIME RESISTANCE RATE CONSTANT 8 7 .5 0 142.50 0.8256E-03 133.25 150.20 0.8449E-03 163.25 154.30 0.8275E-03 198.50 159.60 0.8328E-03 246.00 166.10 0.8302E-03 293.25 172.40 0.8322E-03 331.75 177.40 0.8357E-03 361.25 181.10 0.8381E-03 391.25 184.30 O.8 32 IE-0 3 422.25 187.80 O.8 3 I9E-03 454.75 191.30 0.8308E-03

LEAST SQUARES RATE CONSTANT = 0.8330E-03 AVERAGE RATE CONSTANT = 0.8329E-03 CORRELATION COEFFICIENT = 0.9999 STANDARD DEVIATION FROM MEAN = 0.5007E-05 CONCENTRATION OF REACTANTS = .0422N PREDICTED INFINITE RESISTANCE = 402.00 PREDICTED ZERO RESISTANCE = 127.47 PERCENTAGE OF REACTION FOLLOWED = 48.86

METHOXYACETAMIDE AT 35 DEGS. RUN 3

TIME RESISTANCE 1TATE CONSTANT 59'. 50 134.70 0 .8581E-03 8 4.7 5 139.10 0.8587E-03 131.00 146.40 0.8419E-03 160.50 151.50 0.8578E-03 195.25 156.60 0.8506E-03 243.25 163.80 0.8552E-03 290.00 170.40 0.8569E-03 328.00 175.30 0.8535E-03 358.25 179.30 0.8555E-03 388.25 182.90 0.8529E-03 421.00 186.90 0.8536E-03 451.25 190.40 0.8529E-03

LEAST SQUARES RATE CONSTANT = 0.8538E-03 AVERAGE RATE (CONSTANT = 0 .85 4 0 E-03 CORRELATION COEFFICIENT = 0 . 1000E+01 STANDARD DEVIATION FROM MEAN = 0.4345E -05 CONCENTRATION OF REACTANTS = .0418N PREDICTED INFINITE RESISTANCE = 430.00 PREDICTED ZERO RESISTANCE = 123.81 PERCENTAGE OF REACTION FOLLOWED = 49.11 67

METHOXYACETAMIDE AT k5 DEGS. RUN 1

TIME RESISTANCE RATE CONSTANT 31.00 260.00 0.1843E-02 53.00 266.80 0.1853E-02 7 2.0 0 272.70 0.1874E-02 89.25 277.50 0.1854E-02 108.50 283.20 0 . 1867E-02 168.00 299.00 0.1849E-02 182.50 303.00 0.1859E-02 201.75 307.90 0 . 1860E-02 217.00 311.60 0.1856E-02 240.75 317.80 0.1870E-02 272.50 324.70 0 . 1852E-02

LEAST SQUARES RATE CONSTANT = 0.1859E-02 AVERAGE RATE CONSTANT = 0.1858E-02 CORRELAT ION COEFFICIENT = 0 . 1000E+01 STANDARD DEVIATION FROM MEAN = O.8 9 IIE -0 5 CONCENTRATION OF REACTANTS = .0178N PREDICTED INFINITE RESISTANCE = 726.00 PREDICTED ZERO RESISTANCE = 250.21 PERCENTAGE OF REACTION FOLLOWED = 35.01

METHOXYACETAMIDE AT 45 DEGS. RUN 3

TIME RESISTANCE RATE CONSTANT 28.75 265.30 0.1890E-02 50.25 271.60 0 .1 8 1 5E-02 69.00 277.40 0.1827E-02 88.50 283.40 0.1842E-02 107.50 289.00 0.1845E-02 129.00 295.30 0.1854E-02 164.75 305.20 0.1855E-02 179.50 308.70 0.1837E-02 199.50 314.20 0 . 1848E-02 214.00 317.60 0.1837E-02 238.25 323.80 0.1842E-02 269.25 331.40 0.1845E-02 LEAST SQUARES RATE CONSTANT = 0.1844E-02 AVERAGE RATE CONSTANT = 0.1845E-02 CORRELATION COEFFICIENT = 0.9999 STANDARD DEVIATION FROM MEAN = 0 .1 7 18E-04 CONCENTRATION OF REACTANTS = .0178N PREDICTED INFINITE RESISTANCE = 750.30 PREDICTED ZERO RESISTANCE = 255.71 PERCENTAGE OF REACTION FOLLOWED = 34.65

-I* * Vr 68

METHOXYACETAMIDE AT 55 DEGS. RUN 1

TIME RESISTANCE RATE CONSTANT 41.00 221.60 0.3457E -02 60.50 230.40 0.3439E-02 8 2 .2 5 239.80 0.3434E-02 100.50 247.30 0.3430E-02 116.75 253.70 0.3425E-02 146.25 265.40 0.3463E -02 176.75 275.70 0.3432E-02 201.00 284.00 0.3443E-02 225.25 291.50 0.3433E-02 252.00 300.00 0.3453E-02 275.25 306.40 0.3440E-02 301.75 313.50 0.3433E-02

LEAST SQUARES RATE CONSTANT SS 0.3440E-02 AVERAGE RATE CONSTANT B 0.3440E-02 CORRELATION COEFFICIENT ss 0.1000E+01 STANDARD DEVIATION FROM MEAN B 0 .1 127E-04 CONCENTRATION OF REACTANTS S .0191N PREDICTED INF IN ITE RESISTANCE B 598.40 PREDICTED ZERO RESISTANCE B 201.30 PERCENTAGE OF REACTION FOLLOWED B 53.93 *

METHOXYACETAMIDE AT 55 OEGS. RUN 2

TIME RESISTANCE RATE CONSTANT 3 8.2 5 229.50 0.3444E-02 57.50 239.00 0-.3459E-02 79.50 249.30 0.3464E-02 97.50 257.20 O.3456E-O2 117.75 265.80 0.3455E-02 143.25 276.10 O.3456E-O2 173.75 287.80 0.3462E-02 198.25 296.90 O.3 4 77E-02 222.75 304.90 0.3459E-02 248.75 313.20 0.3453E-02 272.75 320.60 0.3453E-02 298.75 328.30 O.3455E-O2

LEAST SQUARES RATE CONSTANT B O.3458E-O2 AVERAGE RATE 'CONSTANT B O.3458E-0 2 CORRELATION COEFFICIENT = 0 . 1000E+01 STANDARD DEVIATION FROM MEAN B O.7 6 I 6E-O5 CONCENTRATION OF REACTANTS = .OI9 IN PREDICTED INF INITE RESISTANCE = 636.84 PREDICTED ZERO RESISTANCE S 209.48 PERCENTAGE OF REACTION FOLLOWED = 53.93 •>v 69

CYCLOHEXANECARBOXAMIDE AT 75 DEC-S RUN 1

T IME RESISTANCE RATE CONSTANT 193.25 60:40 0.4552E-03 292.00 63.20 0.4276E-03 383.00 65.70 0 .4 1 65E-03 468.00 63:20 0.4187E-03 598.50 71.80 0.4207E-03 719.50 74.70 0 .4 1 69E-03 1440.75 90.10 0.4281E-03 1518.75 91.50 0.4293E-03 160 3.00 92.90 0.4282E-03 1730.75 94.70 0.4262E-03 1823.50 96.10 0.4264E-03 190«.00 97.40 0.4277E-03 1996.75 98.60 0.4271E-03 2982.00 109.50 0.4220E-03

LEAST SOUARES RATE CONSTANT = 0.4257E-03 AVERAGE RATE CONSTANT = 0.4265E-03 CORRELATION COEFFICIENT = 0.9996 STANDARD DEVIATION FROM MEAN = 0.9034E-05 CONCENTRATION OF REACTANTS = .0420N PREDICTED INFINITE RESISTANCE = 166:75 PREDICTED ZERO RESISTANCE = 53.07 PERCENTAGE OF REACTION FOLLOWED = 75.59 ^ A

CYCLOHEXANECARBOXAMI DE AT 75 DECS RUN 2

TIME RESISTANCE RATE constant 193.00 59.20 0.4451E-03 292.50 62.10 0.4259E-03 382.25 64.60 0.4178E-03 1*68.00 67.00 0 .4 1 69E-03 598.25 70.60 0.4206E-03 719.00 73.40 0 .4 1 53E-03 11*1*0.00 88,60 0.4263E-03 1519.00 90.00 0.4275E-03 1608.75 91.50 0.4282E-03 1730.75 93:30 0.4267E-03 1822.75 94.50 0.4240E-03 1907.75 95.90 0.4270E-03 1999.00 97.00 0.4245E-03 2982.25 107.70 0.41S2E-03 LEAST SQUARES RATE CONSTANT = 0.4241E-03 AVERAGE RATE CONS!ANT = 0.4246E-03 CORRELA'ION CuEFFICIEN! = 0.9995 standard DEVIATION FROM MEAN = 0.7106E-05 CONCENTRATION OF REACTANTS = .0420N PREDICTED INFINITE RESISTANCE = 165.00 PREDICTED ZERO RESISTANCE = 52.13 PERCENTAGE OF REACTION FOLLOWED = 75.43 7 0

CYCLOHEXANECARBOXAHI DE AT 85 DEGS RUN 1

TIME RESISTANCE RATE CONSTANT 58.50 67.70 0.651 IE-03 122.75 7 2.3 0 0 . 6435E-03 166.25 74.90 0 . 6226E-03 226.25 78; 60 0.6202E-03 290.00 82.50 0.6268E-03 330.25 85.00 0.6355E-03 378.75 37.70 0.63S3E-03 437.50 90.80 0.6409E-03 1411.50 123.40 0.6328E-03

LEAST SQUARES RATE CONSTANT = 0.6336E-03 AVERAGE RATE CONSTANT = 0.6346E-03 correlation coefficient = 0.9998 standard d e v ia t io n from mean = 0.9562E-05 CONCENTRATION OF REACTANTS = .0506N PREDICTED INFINITE RESISTANCE = 193.75 PREDICTED ZERO RESISTANCE = 63.09 PERCENTAGE OF REACTION FOLLOWED = 72.47

CYCLOHEXANECARBOXAMIDE AT 85 DEGS RUN 2

T IME r e s is ta n c e RATE CONSTANT 56; 50 68.30 0 ; 6494E-03 120.75 72.60 0 .6 1 24E-03 165.50 75.40 0.6019E-03 224;25 79; 10 0.6035E-03 290.00 83.10 0 ; 6088E-03 328.00 85.40 0.6145E-03 376.75 83.20 0 .6 1 95E-03 435.75 91 ; 30 O'. 6209E-03 1410.00 124.60 0.6137E-03

LEAST SQUARES RATE CONSTANT = 0.6142E-03 AVERAGE RATE CONSTANT = 0.6161E-03 correlation coefficient = 0.9998 STANDARD DEVIATION FROM MEAN = 0.1325E-04 CONCENTRATION OF REACTANlS .0506N PREDICTED INFINITE RESISTANCE 199.04 PREDICTED ZERO RESISTANCE 63.77 PERCENTAGE OF REACTION FOLLOWED 71.84 71

CYCLOHEXANECARBOXAMI DE Al 95 DECS RUM 1

T IME RESISTANCE rate constant 49.25 64.30 0.1244E-02 79.75 68.10 0.1257E-02 108.25 71.00 0 .1 220E-02 135.00 73.70 0 .1 209E-02 166.00 76.70 0.1204E-02 198.00 30.20 0.1241E-02 231.25 83.20 0.1245E-02 255.50 85.30 0 .1 249E-02 280.50 87.40 0.1254E-02 312.75 39.30 0.1224E-02 348.50 92.00 0 .1 232E-02 374.25 93.70 0 .1 230E-02 399.75 95.30 0.1227E-02

LEAST SQUARES RATE CONSTANT = 0.1233E-02 AVERAGE RATE constant = 0.1253E-02 CORRELATION COEFFICIENT = 0.9993 STANDARD DEVI AT ION FROM MEAN = 0.1595E-04 concentration OF reactants = .0508N PREDICTED INF INITE RESISTANCE = 173.46 PREDICTED ZERO RESISTANCE = 57.75 PERCENTAGE OF REACTION FOLLOWED = 59.07 /V Vc V-c

CYCLOHEXANECARBOXAMIDE AT 95 DECS RUN 2

TIME resistance rate constant 47.00 63.30 0;1291E-02 78.00 66. 7 O 0 .12 1 6E-02 106.50 69.60 0 .1 180E-02 132.75 7 2 . 60 0.1200E-02 164;00 7 6 ; 20 0 .1 233E-02 1 95'.75 79; 40 0.1241E-02 229.50 82; 40 0 .1 235E-02 2 5V. 00 84; 30 0 ;1 222E-02 278;50 86; 60 0 ;1 236E-02 310.75 89; 10 0 .1 233E-02 346.25 91.60 0.1226E-02 372.25 93.40 0 ;1 224E-02 398.00 95.00 0 .1 217E-02 LEAST SQUARES RATE CONSTANT = 0.1226E-02 AVERAGE RATE CONSTANT = 0 . 1227E-02 CORRELATION COEFFICIENT = 0.9994 standard deviation from mean = 0.2423E-04 CONCENTRATION OF REACTANTS = .0505N PREDICTED INFINITE RESISTANCE = 181.30 PREDICTED ZERO RESISTANCE = 56.75 PERCENTAGE OF REACTION FOLLOWED = 58.61 72

CYCLOPENTANECARBOXAMIDE AT 75 DEGS. 1

TIME RESISTANCE RATE CONSTANT 104.25 7 2.80 O.8 3 I 8E-O3 214.50 80.30 0.7679E-03 334.50 87.40 0.7454E-03 456.50 94.10 0.7469E-03 576.00 100.00 0.7523E-03 695.75 105.00 0 .75 0 1 E-0 3 1426.75 128.00 0 .7 8 58E-03 1539.50 130.20 0 .78 1 8 E-03 1666.75 132.60 0.7807E-03 1773.75 134.30 0.7755E-03 1893.75 136.40 0.7785E-03 2124.25 139.50 0.7702E-03 2788.25 146.20 0.7418E-03

LEAST SQUARES RATE CONSTANT = 0.7677E-03 AVERAGE RATE CONSTANT = 0-.7699E-03 CORRELATION COEFFICIENT = 0-.9976 STANDARD DEVIATION FROM MEAN = 0.2332E-04 CONCENTRATION OF REACTANTS = •0493N PREDICTED INFINITE RESISTANCE = 187.50 PREDICTED ZERO RESISTANCE = 63.13 PERCENTAGE OF REACTION FOLLOWED = 85.66

CYCLOPENTANECARBOXAMIDE AT 75 DEGS. 2

TIME RESISTANCE RATE CONSTANT 103.75 76.40 0.8650E-03 215.00 84; 20 0 .7751E-03 334.50 92.30 O.77 2 3 E-03 456.25 99.70 0.7783E-03 576.25 105.90 0.7773E-03 696.OO 111.70 0 .78 5 3 E-03 1426;50 135.90 0.8076E-03 1540.25 138.40 0.8063E-03 1667;25 141.00 0.8058E-03 1773.75 142.80 0 .8 0 0 1 E-03 1895.00 144.80 0.7964E-03 2125.00 148.20 0.7897E-03 2790.25 155.90 0.7734E-03 LEAST SQUARES RATE CONSTANT =3 0-.7926E-03 AVERAGE RATE CONSTANT = 0.7948E-03 CORRELATION COEFFICIENT = 0.9983 STANDARD DEVIATION FROM MEAN = 0.2390E -04 CONCENTRAT ION OF REACTANTS = .0494N PREDICTED INF IN ITE RESISTANCE = 199.65 PREDICTED ZERO RESISTANCE ss 65.85 PERCENTAGE OF REACTION FOLLOWED = 86.19 * * 73

CYCLOPENTANECARBOXAMIDE AT 85 DEGS. 1

TIME RESISTANCE RATE CONSTANT 43; 00 59.00 0.1432E -02 105.50 64.20 0.1310E -02 164.00 68 ; 80 0.1302E -02 224.75 73.60 0.1340E -02 279.75 77.30 0.1344E -02 3 28.75 80; 60 0.1366E -02 374.25 83.30 0.1372E -02 419.25 85.70 0.1372E -02 463.50 88.10 0.1383E -02 527.50 91.30 0 ; 1397E-02 1270.75 11 2;50 0 ; 1358E-02 1328.75 113.40 0.1346E -02 1382.00 114.20 0 . 1337E-02

LEAST SQUARES RATE CONSTANT = 0;1357E-02 AVERAGE RATE CONSTANT = 0 .1358E-02 CORRELATION COEFFICIENT = 0.9989 STANDARD DEVIATION FROM MEAN = 0.3348E-04 CONCENTRATION OF REACTANTS = .0382N PREDICTED INFINITE RESISTANCE = 156.00 PREDICTED ZERO RESISTANCE = 54.37 PERCENTAGE OF REACTION FOLLOWED = 80.42

CYCLOPENTANECARBOXAMIDE AT 85 DEGS. 3

TIME RESISTA RATE CONSTANT 57; 50 80.00 0 ; 1398E-02 124.25 87'.90 0 ; 1347E-02 187.00 94; 20 0; 1312E-0 2 244;00 100.00 0.1333E-02 304;25 105;60 0.1350E-02 359.50 110;00 0.1349E-02 420.75 114.70 0 ; 1360E-02 473.00 118.30 0 . 1363E-0 2 538;00 122.70 0 ; 1379E-02 598.50 126.00 0.1373E-02 6 7 6 .OO 130.20 0.138 IE-02 1444.00 154.40 0.1326E-02

LEAST SQUARES RATE CONSTANT 0.1355E -02 AVERAGE RATE CONSTANT 0.1356E -02 CORRELATION COEFFICIENT 0.9986 STANDARD DEVIATION FROM MEAN 0.2379E -04 CONCENTRATION OF REACTANTS .0401N PREDICTED INFINITE RESISTANCE 208.00 PREDICTED ZERO RESISTANCE 71.72 PERCENTAGE OF REACTION FOLLOWED 81.73 74

CYCLOPENTANECARBOXAMIDE AT 95 DEGS. 1

TIME RESISTANCE RATE CONSTANT 125.00 68.50 0.2687E-02 184.75 75.30 0.2705E -02 246.75 81.00 0.2693E-02 302;00 85.40 0-.2694E-02 349.00 88.80 0.2707E-02 395.00 91.70 0.2710E -02 439.50 94.00 0.2686E-02 485.00 96.50 0.2705E -02 548.00 99.20 0.2684E -02

LEAST SQUARES RATE CONSTANT = 0.2697E-02 AVERAGE RATE CONSTANT = 0.2697E-02 CORRELATION COEFFICIENT = 0.9997 STANDARD DEVIATION FROM MEAN = 0.97 52E-05 CONCENTRATION OF REACTANTS = .0382N PREDICTED INFINITE RESISTANCE = 144.00 PREDICTED ZERO RESISTANCE = 49.30 PERCENTAGE OF REACTION FOLLOWED = 76.49

A

CYCLOPENTANECARBOXAMIDE AT 95 DEGS. 2

TIME RESISTA RATE CONSTANT 71-25 91.20 0 .2 8 1 5E -02 124:50 100:80 0.273 IE-02 183:50 109:80 0.2715E-02 245:50 118:40 0.2780E-02 300 :50 1 24:20 0.2764E-02 348:25 129.00 0.2791E-02 395.25 133:10 0 ; 2806E-02 439.00 136:20 0.2790E-02 484:00 138:90 0.2759E -02 547.25 142.40 0.2731E-02

LEAST SQUARES RATE CONSTANT 0 ; 2768E -0 2 AVERAGE RATE CONSTANT 0.2768E-02 CORRELATION COEFFICIENT 0.9989 STANDARD DEVIATION FROM MEAN 0.3245E -04 CONCENTRATION OF REACTANTS .0382N PREDICTED INFINITE RESISTANCE 198.65 PREDICTED ZERO RESISTANCE 73.55 PERCENTAGE OF REACTION FOLLOWED 76.78 * 75

a-METHYBUTYRAMIDE AT 75 DEGS. RUN 1

TIME RESISTANCE RATE CONSTANT 88.50 45.70 0 : 1 9 1 0 E- 0 3 265.25 49.00 0;1642E-03 452.50 52.30 0.1601E-03 540:25 53:60 0.1564E-03 690.50 5 6 ; 20 O.I5 9 OE-O3 1409:75 66.70 0.1651E-03 1588.25 68 ; 80 0 : 1 6 5 1 E—03 1760.50 70.80 0 :I 6 6 0 E- 0 3 1865.50 71.90 0 : I 6 5 9 E- 0 3 2050:25 73:60 0.1647E-03 2870.00 80:70 0 .I 6 5 6 E- 0 3 2962:25 81.20 0.1642E-03 3186.25 82.10 0.1591E-03 LEAST SQUARES RATE CONSTANT = 0-.1637E-03 AVERAGE RATE CONSTANT = 0:1651E-03 CORRELATION COEFFICIENT = 0.9990 STANDARD DEVIATION FROM MEAN = 0.8082E-05 CONCENTRATION OF REACTANTS = .0794N PREDICTED INFINITE RESISTANCE = 131:75 PREDICTED ZERO RESISTANCE = 43.47 PERCENTAGE OF REACTION FOLLOWED = 70.22

* *

3.-METHYLBUTYRAM I DE AT 75 DEGS. RUN 2

TIME RESISTANCE RATE CONSTANT 87'.75 47:30 0.1965E-03 263:50 50.70 0 : 1652E-0 3 450:00 54:10 0 . 1598E-03 538.50 55:70 0 . 1599E-03 688 ; 50 58.30 0 . 1603E-0 3 1411:75 69:30 0 .I 650E-0 3 1586.50 7 1 :7 0 0: 1671E-0 3 1761:50 73.70 0: 1667E-03 1866:50 74:90 0 . 1670E-03 2052:75 77:00 0 . 1680E-03 2868:50 84.20 0 : 1667E-03 2960:50 84.80 0 ; 1658E-03 3187.50 85.80 0.1609E-03

LEAST SQUARES RATE CONSTANT 0 : 1652E-03 AVERAGE RATE CONSTANT 0 :1668E-03 CORRELATION COEFFICIENT 0.9991 STANDARD DEVIATION FROM MEAN 0.9050E -05 CONCENTRATION OF REACTANTS .0795N PREDICTED INFINITE RESISTANCE 138:60 PREDICTED ZERO RESISTANCE 44.92 PERCENTAGE OF REACTION FOLLOWED* 70.49 * 76

â-METHYLBUTYRAMIDE a ï 85 DEGS. RUN 1

TIME RESISTANCE RATE CONSTANT 90.00 44.70 0.3636E-03 181'25 47'.60 0.3279E -03 2 70 .00 50; 80 0.3390E -03 366.00 53;70 0.3368E -03 456;50 56.50 0-.3431E-03 542.50 58.90 0.3460E-03 692.50 62.40 0 .3 4 3 1E-03 1413.50 75.10 0.3423E-03 1504.75 76.30 0 .3 4 1 9E-03 1591.75 77.40 0.3418E-03 I 6 9 4 . 2 5 78.60 0.3413E-03 1770.50 79.50 0.3418E-03 1878.00 80.60 0.3406E-03

LEAST SQUARES RATE CONSTANT = 0.3417E-03 AVERAGE RATE CONSTANT = 0-.3422E-03 CORRELATION COEFFICIENT = 0.9998 STANDARD DEVIATION FROM MEAN = 0.7442E -05 CONCENTRATION OF REACTANTS = •0795N PREDICTED INFINITE RESISTANCE = 120.13 PREDICTED ZERO RESISTANCE = 40.82 PERCENTAGE OF REACTION FOLLOWED = 74.76

3.-METHYLBUTYRAMIDE AT 85 DEGS. RUN 2

TIME RESISTANCE RATE CONSTANT 88; 75 45; 60 0.3413E-03 179.50 48; 80 O.326OE-O3 268.00 52; 00 0 .33 2 1 E-0 3 366.00 55.00 O.3276E-O3 454.50 57.70 0.3297E-03 541;25 60.30 0.3341E-03 692.50 64; 20 O.3 34 7E-O3 141 2; 50 78.10 0.3352E-03 1503.25 79:30 O.3329E-O3 1590.25 8 0.70 0-.3354E-03 1693;oo 81.90 O.3326E-O3 1769.25 82.60 0.3284E-03 1877.00 83.90 0 .32 8 1 E-0 3

LEAST SQUARES RATE CONSTANT = 0.3320E-03 AVERAGE RATE CONSTANT = 0.3322E-03 CORRELATION COEFFICIENT = 0.9997 STANDARD DEVIATION FROM MEAN = 0.4010E-05 CONCENTRAT ION OF REACTANTS = .0770N PREDICTED INF 1N ITE RESISTANCE = 131.75 PREDICTED ZERO RESISTANCE = 41.88 PERCENTAGE OF REACTION FOLLOWED = 7 3 .4 2 77

3.-METHYLBUTYRAMIDE AT 95 DEGS. RUN 1

TIME RESISTANCE RATE CONSTANT 106.50 32:00 0.6060E-03 160:00 33.90 0.5832E-03 225.50 36:20 0-.5815E-03 283.50 38.30 0.5957E-03 344:00 40.10 0:5932E-03 390:00 41:40 0.5929E-03 435.50 42.70 0: 5972E-03 547:25 45:40 0.5958E-03 610.00 46:70 0.5920E-03 667.25 47.80 0.5885E-03

LEAST SQUARES RATE CONSTANT = 0.5924E-03 AVERAGE RATE CONSTANT = 0.5926E-03 CORRELATION COEFFICIENT = 0:9996 STANDARD DEVIATION FROM MEAN = 0.6722E-05 CONCENTRATION OF REACTANTS = .O76ON PREDICTED INFINITE RESISTANCE = 85:20 PREDICTED ZERO RESISTANCE = 27.18 PERCENTAGE OF REACTION FOLLOWED = 63.35

/V

3.-METHYLBUTYRAMI DE AT 95 DEGS. RUN 2

TIME RESISTANCE RATE CONSTANT 44:00 28:40 0-.5956E-03 107:50 30:80 0:5728E-03 161.25 32 :50 0-.5514E-03 227:25 34:70 0:561 IE-03 284.75 36:60 O.5766E-O3 345:00 38:20 0 : 5734E-03 391.50 3 9:50 0.5805E-03 436:50 40:60 0-.5813E-03 548:50 43:00 0-.5788E-03 611:50 44:00 0.5670E-03 669.25 45.00 0.5644E-03 LEAST SQUARES RATE CONSTANT = 0:5720E-03 AVERAGE RATE 'CONSTANT = 0.5730E-03 CORRELATION COEFFICIENT = 0:9992 STANDARD DEVIATION FROM MEAN = 0.1128E-04 CONCENTRAT ION OF REACTANTS = .0764N PREDICTED INF IN ITE RESISTANCE = 77.50 PREDICTED ZERO RESISTANCE = 26.46 PERCENTAGE OF REACTION FOLLOWED = 62.57 78

ISO-BUTYRAMIDE AT 75 DEGS. RUN 1

TIME RESISTANCE RATE CONSTANT 162.75 97.90 0;6882E-03 229.25 102.60 0.6802E-03 3 2 1 .25 109;00 0 .6 8 50E-03 391;50 112.80 0.6659E-03 47O.OO 117.60 0.6704E-03 638.50 127.00 0-.6776E-03 7 09 .2 5 130.80 0.6836E-03 7 82 .2 5 134.10 0.6810E-03 1438;75 158.80 0 .68 5 9 E-03 1547.00 161 ;60 0 .68 0 1 E-03 1675.25 164.60 0.6723E-03

LEAST SQUARES RATE CONSTANT ■ 0;6788E-03 AVERAGE RATE CONSTANT ' 0.6791E-03 CORRELATION COEFFICIENT ■ 0.9997 STANDARD DEVIATION FROM MEAN : 0.6666E-05 CONCENTRATION OF REACTANTS : .0382N PREDICTED INFI NITE RESISTANCE 263 ‘.50 PREDICTED ZERO RESISTANCE Sif.57 PERCENTAGE OF REACTION FOLLOWED 71.60

•J*

BUTYRAMIDE AT 75 DEGS . RUN 2

TIME RESISTANCE RATE CONSTANT 161.00 96;80 0.6484E-03 227‘.7 5 101.20 0.6392E-03 319;2 5 106;90 0-.6342E-03 389;50 111 ; 20 0;6375E-03 468.00 115.50 0.6344E-03 636.25 1 24;20 0.6362E-03 707.50 127.80 0 .6 4 1 2E-03 780.25 131.10 0-.6419E-03 1437.00 154.70 0 .6 4 4 3 E-03 1545.25 157.30 0;6373E-03 1673.25 160.60 0.6360E-03 LEAST SQUARES RATE CONSTANT . 0-.6389E-03 AVERAGE RATE CONSTANT : 0 . 6391E-03 CORRELATION COEFFICIENT : 0.9999 STANDARD DEVIATION FROM MEAN : 0.4200E-05 CONCENTRATION OF REACTANTS : .0382N PREDICTED INFINITE RESISTANCE : 258;40 PREDICTED ZERO RESISTANCE 84.46 PERCENTAGE OF REACTION FOLLOWED 70.43

■/V 7 9

ISO-BUTYRAMIDE AT 85 DEGS. RUN 1

TIME RESISTANCE RATE CONSTANT 46:25 74.80 0 ; 1 132E-02 102:75 81:10 0.1100 E-0 2 173.00 88:30 0 ;1097E-02 231:50 93:70 0 . 1095E-02 289:00 98:80 0 ; 1 105E-02 350:25 103:90 0; 1117 E-0 2 410.75 108:40 0 ;1121E-02 466:50 112:00 0 ;1 1 16E-02 527.75 115:70 0 .1 1 1 2E-02 589:75 119:10 0 ; 1 106E-02 642:25 122.00 0 ; 1 108E-02 693.00 124.20 0 .1 0 9 7 E -0 2

LEAST SQUARES RATE CONSTANT = 0;1108E -0 2 AVERAGE RATE CONSTANT = 0 ; 1 IO9E-O2 CORRELATION COEFFICIENT = 0;9997 STANDARD DEVIATION FROM MEAN = O .IO 7 2E-0A CONCENTRATION OF REACTANTS = .0437N PREDICTED INF IN ITE RESISTANCE = 212; 50 PREDICTED ZERO RESISTANCE = 68.86 PERCENTAGE OF REACTION FOLLOWED = 65.92

ISO-BUTYRAMIDE AT 85 DEGS. RUN 2

TIME RESISTANCE RATE CONSTANT 44:75 72.90 0 ;1 135E-02 100.75 78:90 0.1091E-02 170-.75 85:60 0 .10 7 1 E-02 230.00 91:30 0; 1094E-02 287.00 95:80 0.1084E -02 348.75 101.00 0; 1106E-02 409.50 105:20 0.1104E-02 464.75 108.60 0 . 1097E-02 526.50 112:60 0 .1 1 0 7 E-02 587.7 5 115.60 0 ; 1092E-02 640.50 118.40 0.1094E -02 690.75 120.70 0.1089E -02 LEAST SQUARES RATE CONSTANT = 0 .10955-02 AVERAGE RATE CONSTANT = 0.1097E -02 CORRELATION COEFFICIENT = 0:9997 STANDARD DEVIATION FROM MEAN = 0 . 1484E-04 CONCENTRATION OF REACTANTS = .0437N PREDICTED INFINITE RESISTANCE = 206:25 PREDICTED ZERO RESISTANCE = 67.28 PERCENTAGE OF REACTION FOLLOWED = 65.69

/V /\ 80

SO-BUTYRAMIDE AT 95 DEGS . RUN 1

TIME RESISTANCE RATE CONSTANT 63'. 50 72.60 0. 1938E-0 2 95.50 77.20 0. 1916E-02 121.25 80.80 0.1931E -02 151.00 84.50 O.I927E-O2 182.25 88; 20 0.1936E -02 212.00 91.60 0.1956E -02 240.00 94.00 0.1923E -02 276.75 97.60 0 .1 9 4 3 E -0 2 305.00 100.00 0-.1942E-02 330.50 102.10 0 .1 9 4 7 E -0 2 361.50 104.20 0.1930E -02 392.25 106.10 O.I9IIE -02 LEAST SQUARES RATE CONSTANT s 0 ; 1934E-02 AVERAGE RATE CONSTANT S3 0.1933E -02 CORRELATION COEFFICIENT ss 0-.9996 STANDARD DEVIATION FROM MEAN ss 0 . 1 245E-04 CONCENTRAT ION OF REACTANTS ss .0432N PREDICTED INFI NITE RESISTANCE ss 172.50 PREDICTED ZERO' RESISTANCE s 61.62 PERCENTAGE OF REACTION FOLLOWED S3 65.22

J-é\ * />

E AT 95 DEGS. RUN 2

TIME RESISTANCE RATE CONSTANT 31.50 69:40 0.2073E-02 62; 25 74:70 0 : 1963E-02 94; 7 5 80.00 0;1951E—02 121.00 84:00 0.1954E-02 149:75 88:20 0 .1 9 7 1 E—0 2 18 1 ; 25 92:40 0 ; 1982E-02 211:25 96.10 0.1991E-02 239.00 99.40 0;2007E-02 275.75 103.10 0;2001E-02 303.50 105.70 0 ; 1998E-02 329.50 IO7 . 9O 0 ; 1989E-02 361.00 110.50 O.I 986E-0 2 391.00 112.40 0.1956E-02 LEAST SQUARES RATE CONSTANT = 0.1984E -02 AVERAGE RATE CONSTANT = 0.1986E -02 CORRELATION COEFFICIENT = 0:9995 STANDARD DEVIATION FROM MEAN = 0.3076E-04 CONCENTRATION OF REACTANTS = .0454N PREDICTED INFINITE RESISTANCE = 185.73 PREDICTED ZERO RESISTANCE = 62.66 PERCENTAGE OF REACTION FOLLOWED = 66.78 * 81

TRIMETHYLACETAMIDE AT 75 DEGS. RUN 1

TIME RESISTANCE RATE CONSTANT 246.25 86.00 0.2723E-03 429.25 90.90 0.2590E-03 575.50 94.50 0.2532E-03 718.00 98.40 0 .2581E-03 1434.00 114.00 0.2591E-03 1609.00 117.40 0.2605E-03 1742.25 120.20 0.2645E-03 1893.25 122.30 0.2607E-03 2135.25 126.20 0.2613E-03 2868.50 136.10 0.2603E-03 2976.25 137.20 0.2588E-03

LEAST SQUARES RATE CONSTANT B 0.2603E-03 AVERAGE RATE CONSTANT s 0.2607E-03 CORRELATION COEFFICIENT s s 0.9997 STANDARD DEVIATION FROM MEAN s s 0.450 IE-05 CONCENTRATION OF REACTANTS s .043 2N PREDICTED INF IN ITE RESISTANCE = 225.40 PREDICTED ZERO RESISTANCE s 77.83 PERCENTAGE OF REACTION FOLLOWED s s 66.10

■Ä- "A- '>v

TRIMETHYLACETAMIDE AT 75 DEGS. RUN 2 TIME RESISTANCE RATE CONSTANT 251.25 56.60 0.2645E-03 435.00 59.60 0.2516E-03 580.50 61.90 0.2487E-03 722.25 64.10 0.2485E-03 1439.00 74.00 0.2515E-03 1614.00 76.20 0.2533E-03 1747.50 77.80 0.2545E-03 1899.50 79.50 0.2552E-03 2140.75 82.00 0.2555E-03 2874.00 88.30 0.2524E-03 2976.75 89.00 0.2511E-03

LEAST SQUARES RATE CONSTANT s s 0.2530E-03 AVERAGE RATE CONSTANT = 0.2533E-03 CORRELATION COEFFICIENT =s 0.9997 STANDARD DEV LM ION FROM MEAN = 0.4177E-05 CONCENTRATION OF REACTANTS = .0400N PREDICTED INF IN ITE RESISTANCE = 152.00 PREDICTED ZERO RESISTANCE =5 51.56 PERCENTAGE OF REACTION FOLLOWED = 63.66 * TRIMETHYLACETAMIDE AT 85 DEGS. RUN 1A

TIME RESISTANCE RATE CONSTANT 150.00 53.40 0.5109E-03 237.00 56.30 0.5099E-03 331.00 59.20 0.5088E-03 421.00 61.80 0.5090E-03 516.50 64.40 0.5102E-03 602.00 6 6 .6 0 0 .5118E-03 717.50 69.60 0 . 5 2 0 9 E- 0 3 1433.50 82.50 0.5173E-03 1504.50 83.30 0.5120E-03 1600.00 84.40 0.5072E-03 1688.75 8 5 .6 0 0.5084E-03 LEAST SQUARES RATE CONSTANT = 0.5117 E—03 AVERAGE RATE CONSTANT = 0 .5115E-03 CORRELATION COEFFICIENT = 0.9997 STANDARD DEVIATION FROM MEAN = 0.3919E-05 CONCENTRATION OF REACTANTS = .0432N PREDICTED INFINITE RESISTANCE = 135.00 PREDICTED ZERO RESISTANCE = 47.83 PERCENTAGE OF REACTION FOLLOWED = 68.33 * * >v

TRIMETHYLACETAMIDE AT 85 DEGS. RUN 2A

TIME RESISTANCE RATE CONSTANT 54.00 50.80 0.5834E-03 149.75 53.70 0.4822E-03 237.00 56.60 0.4891E-03 330.50 59.50 0.4931E-03 421.00 62.20 0.4992E-03 516.25 64.90 0.5056E-03 602.25 67.10 0.5071E-03 717.50 70.00 0.5136E-03 1434.25 82.60 0.5047E-03 1504.50 83.60 0.5049E-03 1600.00 84.80 0.5027E-03 1689.00 85.80 0.4992E-03 LEAST SQUARES RATE CONSTANT = 0.5033E-03 AVERAGE RATE CONSTANT = 0.507 IE-03 CORRELATION COEFFICIENT = 0.9996 STANDARD DEV IATI ON FROM MEAN = 0.2444E-04 CONCENTRATION OF REACTANTS = .0432N PREDICTED INFINITE RESISTANCE = 135.00 PREDICTED ZERO RESISTANCE = 48.41 PERCENTAGE OF REACTION FOLLOWED = 67.94 S3

TRIMETHYLACETAMIDE AT 95 DEGS. RUN 1

TIME RESISTANCE RATE CONSTANT 109.75 81.10 0.1032E -02 167.50 85.20 0.987 IE-03 229.25 89.80 0.9994E-03 290.00 93.80 0 .99 9 1 E-03 348.75 97.40 0 . 1001E-02 406.75 101.20 0 . 1025E-02 468.00 104.00 0.1007E-02 567.7 5 108.60 0 .10 0 1 E-02 618.50 111.00 0.1009E-02 672.OO 113.20 0.1009E-02 743.00 115.70 0.1001E-02 LEAST SQUARES RATE CONSTANT = 0.1006E-02 AVERAGE RATE CONSTANT = 0.1006E-02 CORRELATION COEFFICIENT = 0.9996 STANDARD DEVIATION FROM MEAN = 0.1191E—04 CONCENTRATI ON OF REACTANTS = .0388N PREDICTED 1NF INITE RESISTANCE = 186.00 PREDICTED ZERC1 RESISTANCE = 70.94 PERCENTAGE OF REACTION FOLLOWED = 62.54

•ar /V JU

TRIMETHYLACETAMIDE AT 95 DEGS. RUN 2 TIME RESISTANCE RATE CONSTANT 53.00 73.70 0.1118 E-0 2 109.50 78.20 0.1039E-02 167.00 82;80 0.1047E-02 228.75 87.40 0.1057E-02 289.75 91.60 0.1067E-02 348.75 95.20 O.IO 67E-O2 406.25 98.40 0 . 1066E-02 468.00 101.80 0.1074E-02 567.25 106.20 0.1063E-02 617.75 108.50 0 . 1068E-02 671.25 110.60 0 . 1066E-02 742.50 113.00 0.1055E-02 LEAST SQUARES RATE CONSTANT 0 . 1064E-02 AVERAGE RATE CONSTANT 0.1066E-02 CORRELATION COEFFICIENT 0.9998 STANDARD DEVIATION FROM MEAN 0.1839E-04 CONCENTRATION OF REACTANTS .0387N PREDICTED INFINITE RESISTANCE 180.00 PREDICTED ZERO RESISTANCE 68.34 PERCENTAGE OF REACTION FOLLOWED 63.71 *