kinetics and mechanisms of base-catalysed reactions

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Masters Theses Student Theses and Dissertations

1966

Kinetics and mechanisms of base-catalysed reactions Kinetics and mechanisms of base-catalysed reactions

Rohit Panalal Sheth

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KINETICS AND MECHANISMS OF

BASE·CATALYSED REACTIONS

By

ROHIT PANALAL SHETH

A

THESIS

submitted to the faculty of

THE UNIVERSITY OF MISSOURI AT ·roLLA

in partial fulfillment of the requirements

for the degree· of

MASTER OF SCIENCE IN CHEMICAL ENGINEERING

Rolla, Missouri

1966

~ ....

TABLE OF CONTENTS

Page

TITLE PAGE • • • • • • • • • • • • • • • • • • • • • • • • • i

TABLE OF CONTENTS • • • • • • • • • • • • • • • • • • • • .ii

LIST OF FIGURES • • • • • • • • I I I I I I I I I • • • • • iv

LIST OF TABLES • • • • • • • • • • • • • • • • • • • • • • • v

GLOSSARY OF TERMS • • • • • • • • •• • • • • • • • • • • • • vi

QIAPTER I. Introduction • • • • • • • • • • • • • • • • • • 1

CHAPTER II. Literature Review • • • • • • • • • • • • • • • 4

CHAPTER III. Theory •••• • • • • • • • • • • • • • • • • 27

CHAPTER IV. Experimental • • • • • • • • • • • • • • • • • 31

A. Purpose of Investigation •• • • • • • • • • • • • • 31

B. Plan of Experimentation • • • • • • • • • • • • • • 32

c. Experimental Set-Up • • • • • • • • • • • • • • • • 32

D. Analytical Techniques • • • •• • • • • • • . . · .. • • 33

1. Gas Chromatography • • •• • • • • • • • • • • 33

2. Operating Conditions • (;

• • • • • • • • • • • • 34

3. Sampling • • • • • • • • • • • • • • • • • • • 34

E. Preparation of calibration Curve • • • • • • • • • 34

F. Experimentation • • • • • • • • • • • • • • • • • • 35

G. Data and Results • • • • • • • • • • • • • • • • • 35

CHAPTER V. Discussion • • • • • • • • • • • • • • • • • • • • 48

A. Discussion of Data and Results • • • • • • • • • • 48

B. Discussion of Michael Mechanism ••••• • • • • • 51

c. Signifi.cance of the Rate Constants for the Reverse Process and of the Principle of Microscopic Reversibility • • • • • • • • • • • • • • • • • • • 58

D. Objections (Reservations) • • • • • • • • • • • • • 61

ii

Page

CHAPTER VI. Conclusions • • • • • • • • • • • • • • • • • • 66

QIAPTER VI I. Summary • • • • • • • • • • • • • • • • • • • 68

APPENDIX A. List of Computer Programs • • • • • • • • • • • 70

1. A Program for the Calculations of Adduct Concentrations • • • • • • • • • • • • • • • • • • 70

2. A Program for the Calculations of Rate and Equilibrium Constants • • • • • • • • • • • • • • • 71

3. A Program for the Calculations of Activation Energies • • • • • • • • • • • • • • • • • • • • • 73

APPENDIX B. List of Computer Programs (Error Calculations). 75

1. A Program for Computing the Effect of Error in Temperature on Activation Energies •••••••• 75

2. A Program for Correcting Equilibrium Rate Constants ••••••••••••• .•••••••• 78

' APPENDIX c. List of Equipment and Materials • • • • • • • • 81

BIBLIOGRAPHY • • • • • • • • • • • • • • • • • • • • • • • • . 83

ACKNOWLEDGEMENTS • •• • • • • • • • • • • • . . .. ........ 86

VITA • • • • • •• • • • • • • • • • • • • • • • • • • • • • • 87

iii

Figure

1.

2.

3.

4.

LIST OF FIGURES

Standard Curve of Area-Ratio as a Function of ~1ole-Ratio • • • • • • • • • • •

Concentration of Adduct as a Function of Time (Run 1) • •

Concentration of Adduct as a Ftmction of Time (Run 2) ••

Concentration of Adduct as a Function of Time (Run 3) ••

• • • • • • • •

• • • • • • • •

• • • • • • • •

S. Concentration of Adduct as a

Page

36

43

44

45

Function of Time (Rtm 4) • • • • • • • • • • 46

6. Concentration of Adduct as a Function of Time (Run 5) •• • • • • • • • • 47

iv

Table

I

II

III

IV

v

VI

VII

LIST OF TABLES

Reported Equilibrium Yield of Adduct at Various Temperatures • • • • ••

Experirental Data for Run 1 • • • •

Experiroontal Data for Run 2 • • • •

Experimental Data for Run 3 • • • •



Page

• • • • • 9

• • • • • 38

• • • • • 39

• • • • • 40

• • • • • 41

• • • • • 42

Dependence of Rate Constants on Temperature • 49

VIII Equilibrium Yields at Various Reaction .Temperatures • • , • • • • • • • • • • • • • 50

IX Activation Parameters • • • • • • • • • • • • 52

X Entropies of Activation of Some Well Studied Reactions • • • • • • • • • • • • • • 53

XI Acidities of Reaction Components • • • • • • 60

XII Rate Constants and Entropies of Activation as Functions of Ionization Constants ••••• 60

XIII Theoretical Values for ~S~Reaction • • • • • 62

v

Ea

6F*

6H*

h

Ke

Ka

Kb

Km

R

6S*

T

f

r

GLOSSARY OF TERMS

Arrhenius activation energy

Free energy of activation

Heat of activation

Plank's constant

Boltzman constant

Rate constant

Equilibrium constant

Dissociation constant for adduct

Dissociation constant for base (~·Buok)

Dissociation constant for malonic ester

Gas constant

Entropy of activation

Absolute reaction temperatu~

SUBSCRIPTS

Forward process

Reverse process

vi

Olapter I

INTRODUCfiON

Base-catalysed reactions normally involve complex series

of transformations. Their kinetics is usually governed by a

variety of equilibria, participating in the overall and con

current processes as well as by competitive side-reactions

that interfere with the normal course of such reactions.

:-.Iechanisms which have been proposed• by and large, are primarily

based on product, by-product and intermediate analyses together

\vith some scattered kinetic and isotopic evidence. In the

cases where kinetic studies have been attempted, highly

complex mechanisms have usually been proposed due to the

frequent necessity of using heterogeneous media or employing

involved mathematical treatments to describe the kinetics

of the base-catalysed reactions. One of the most common

and the least thoroughly studied class of reactions in this

general area is the "Michael Reaction". It is the name

commonly assigned to the base~catalysed addition of an

activated methylene compound, the addendum, to a suitably

activated :olefin, the acceptor, to yield normal or abnormal

and retrogression Michael adducts as illustrated below:

1

y R R y

I I I I CIIR + CH CH CR I II I I

(1) z Ol 0!2 z I I X X

Normal Adduct

R R R X

I I I I CH CH •., CH + CH2 I I II I CH z CR z /" I

X y y

Abnormal Adduct Retrogression Ad ducts

where, Y and Z may be COOR, COR, CONH2, N02, S02R, CN or OIO•Y

and X may be the same or different than z. Even though the

l--lichae 1 reaction has been known since 1887, there are no thorough

kinetic studies reported of typical systems in any abstracted

publication. In the late 1940's studies were begtm by Shafer,

Loeb and Johnson (43) on the abnormal Michael reaction. Later

studies by Korst (25) and by Wulfman (52) indicated the need

for thorough kinetic studies of both abnormal and normal Michael

Reactions before any definitive mechanism could be proposed for

these reactions.

Wulfrnan (52), in his original studies, observed initial

pseudo "first-order" followed by pseudo zero-order kinetic paths

for the normal Michael reaction. These observations were taken

to imply a change from homogeneous to heterogeneous media as the

reaction proceeds coupled with fortuitous relationships between

the various terms required to describe reaction kinetics.

2

~1ehta (31) avoided these problems by using dilute solutions

and by deriving an improved mathematical model for the rate

law, which took into account the acidity of the product and

sol vent as we 11 as that of the starting material. The study

by Mehta (31) of a typical Michael reaction - ethyl crotonate,

dimethyl malonate, t-butyl alcohol (solvent) and potassium

tertiary butoxide (catalyst) with various initial co~ cent rations

of reactants indicated that the kinetics of the system was

consistent with the generally accepted Michael mechanism.

3

The work presented here was undertaken to test the validity

of the existing Michael mechanism through the use of thermodynamic

interpretation of the experimentally obtained kinetic data. The

investigation involved the study of the effect of temperature

variations on the rate of the Michael reaction. Activation

energies and entropies of activation were determined by

conventional methods and their magnitudes were applied to

furnish valuable clues to the true mechanism of the Michael

reaction.

Chapter II

LITERATURE REVIEW

The ~tichael reaction or addition, in its original scope,

is the addition of an addendum or donor containing an active

n~thylene group to a conjugated carbon-carbon double bond (4).

4

It can be adequately described by the reversible and .base

catalysed addition of diethyl malonate (I), an addendum containing

an activated methylene group, to methyl crotonate (II), an acceptor

\"i th an activated double bond, to yield 1,1 - dicarbethoxy - 3 -

carbomethoxy - 2 - methyl -propane (III) (Chart 1). Product

(III) is referred to as the normal Hichael adduct, and the reaction

sequence leading to (III) is known as the normal ~1ichael reaction

or addition.

The scope of the Hichael Reaction has been surveyed by

Conner and ~1cClellan (7) and there have been more recent

extensions of their review. Some of the numerous variations

of the Michael Reaction are indicated in Chart 2.

The reaction is promoted by a variety of bases, usually

present in catalytic amounts, and its synthetic usefulness

resides in the large number of carbanions and alpha-beta

unsaturated carbonyl compounds that may be prepared (36).

In a general form, the Michael Reaction is interpreted as the

addition of a carbanion to a conjugated system so as to give

a resonance-stabilized condensate anion (Chart 3).

COOC2H5 I CH I 2

(2) COOC2IIs

I

diethyl malonate

(3) II

(4) v

CHART 1

MICHAEL REACTIONS

CH3 I CH II t --... -BuOK

+ CH I .. t - BuoA COOCH3

II

roothy1 croton ate

COOC2H5

I ----- CH doubtful

I route

5

CH3 I

COOC2H5 I

Ql CH I I 012 I OJOC2H5 000013

III

1,1 - dicarbethoxY -3 - carbomethoxy -2- · 111ethy1 propane

r3 IH3 CH ----- 01COOC2H5 I CH COOC2H5

. IV coo~" rooc2H5

,)

v

CH I 3 COOCH3 CH I II + 012 C013 I

boc2H5

COOC2H5

VI VII

6

CHART 2

VARIENTS OF THE MICHAEL REACTION (6)

-COOR

-COR

-CONH2

-N02

-so2R Basic Catalyst

-C- CH- L I 1

L2 - Oi - L3

RCOO- -illOR

RCD--CH2-

-roR

NC- -Oi

B2NCO- -illNH2

o2N- -N0 2

RSO -2

-so2R

OCH- -CHO

Ar- L3

R-

H-

Lz

(L = labilizing substituent)

7

CHART 3

A GENERAL FORM OF TilE HICHAEL REACfiON (6)

I -- I I I I -C= c-L1 --:. C -c-L1 -c--c -L

,~ . . I 1 ... -- ~ --- H+ •• ..

Lz Cll L3 L2- CJI-L3 L2-ctt-L3 ~

I -C-CH-L , I 1

L2 cu-L3

(L = labilizing substituent)

In addition to the normal ~lichael adduct (III) in Chart 1,

Page s, the following Hichael products arc known to be formed:

1) The abnormal Michael adduct (V) which is isomeric with

the normal adduct (III), and

2) the retrogression products (VI, VI I) \'llli ch rc sul t from

the reverse ~lichael clevage of the abnormal product (V),

thus differentiating this modification from a simple

reversal of the normal Michael adduct. llo\-.rever, there

is no general agreement about the origin of the rearrange-

ment - retrogression products (2).

The t-lichael acceptors generally tend to under~o addition

reactions with alkoxide anions. This results in the coll\)etition

of the catalyst with the donor for the acceptor molecule (4).

Wul fman (52) observed at least three side reactions that

interfered with the course of the Michael addition of ethyl

crotonate to dimethyl malonate at high catalyst concentration.

He attributed these side reactions to the dimerization of

ethyl crotonate, the addition of solvent to the acceptor (38),

and the formation of the abnormal product. In the cases where

stronger bases are required, it is nonnally appropriate to use

only 0.1 or 0.3 equivalent of the base, to employ low reaction

temperatures ( 25 ° or less) and short reaction times in order to

minimize the side reactions (17). Koelsch (24) reported that

8

only acceptors like acrylates or acetonitrile add alkoxiae anions

avidly enough to interfere with the condensation in the non-hydroxylic

media.

~lost Michael additions are thought to be exothermic, because

a larger yield of addition product is obtained with lowering of

temperature provided that ample time is given for equilibrium to

be attained (18). This generalization, however, is dependent

upon the presence of only minimal resonance stabilization of the

olefinic system of the acceptor. When this stabilization is large,

endothermic processes are to be expected. In his original experiments

with ethyl cinnamate and ethyl malonate, Michael (18) recorded a

high yield of addition product obtained by reaction at room

temperature, and a poor yield obtained by reaction at the boiling

point of the alcoholic solution. Higher temperatures usually

favor rearrangement-retrogression as well as secondary cyclization

reactions. Both of these reduce the yield of normal adduct.

9

\ii th alkoxide catalysts, reaction times of twenty to one hundred

fifty hours at room temperature have been used with good results

(4). Opposite results should be obtained for endothermic Hichael

reactions. Retrogression is also more likely to occur when the

condensation is slO\~; one of the factors causing slow condensation

is the presence of large substituents at the alpha-beta double

bond of the acceptor molecule. This effect is exemplified in

Table I, in which the yield of condensation product obtained

possibly represents the equilibria attained in the reaction.

TABLE I ( 4)

YIELD OF ADDUC.'T AT VARIOUS ll"EMPERATURES

REACTION YIELD OF ADDUCT

Diethyl Malonate + Ethyl Crotonate 65

+ Ethyl Cinnamate 35

+ Ethyl p,f-dimethyl

-acrylate

30

at

70

A tendency toward retrogression can be combated to a degree by

using an excess of one of the reactants, thereby applying the

law of mass action to affect the equilibrium position in the

reaction. Little information on activation energies resulting

from either exothermic or endothermic Michael reactions has

been reported in the literature as of now.

Based on the nature of the alkaline reagents that cause

the ~1icahel condensation to occur, the logical and presently

accepted mechanism of the normal Michael transformation, with

diethyl malonate is outlined in Chart 4. It is assumed that

the base catalyst required for the Hichael addition (here

symbolised by B:) functions to activate the addendum (I) by

converting it to the corresponding anion (VIII)~ The carbanion

(VIII) then attacks the beta carbon atom of the conjugated

system (II) followed by the ultimate addition of a proton from

the sol vent or Wlreacted addendum to the product anion (IX)

to yield the addition product (III).

(5)

CHART 4

GENERALLY ACCEPTED ~1ECHANIS~f OF NORi\fAL MICHAEL REACTION

0-12 (COOC2H5 ) 2+B:. .... . !"' - + :CH(COOC2H5) 2+B:H

VIII

10

,s .,..c =

,_ , ,-(6) c - c • 0 +

II

(7) IX B~H ~

:CH(OOOC2H5 ) 2~ [

VIII

I - c - Qi - c = 0

I Cll(C02C2H5) 2

III

c .. c = c -:.=..-o]

~(C02C2H5)2 IX

11

The overall reaction is often viewed merely as an addition of

the addendum to the C = C double bond (40).

The mechanism has been supported, to some extent, through

kinetic studies carried out on the addition of barbituric

acid to p-nitrostyrene (21) and the addition of hydrocyanic

acid to alpha-beta unsaturated ketones (20). Ingold (18) suggested

that the Hichae 1 ,addition, as conducted through the agency of

sodium ethoxide in ethyl alcohol, follows the pattern of the

addition of hydrogen cyanide by \'lay of cyanide ion to alpha-beta

unsaturated ketones, as in the example kinetically investigated

l.Jy Jones (20). The rate-determining step would then involve the

attack of the anion of the pseudo-acidic active methylene compound

at the bet a-carbon of the alpha-beta unsaturated molecule. The

reaction follows a second-order rate law, the rate being dependent

on the concentrations of unsaturated ketone · and cyanide ion.

CHART 5

Jones - Ingold Mechanism

II

- I - Slow (8) R - c - c = c + CN R - c - c - C - CN

II I I II I I 0 H II 0 ll H

X XI

0 + Fast (9) XI + H R -

II c - Cll2 - CH2 .- CN

XII

An investigation by Kamlet and Glover (21) was undertaken

in order to obtain evidence concerning the Michael mechanisms

and deal with kinetics of these reactions in buffer media under

various conditions of temperature and dielectric constant. The

investigation involved the addition of barbituric acid to a

series of beta-nitrostyrenes in slightly acidic media. Although

seemingly atypical in that these reactions took place in

non-alkaline media, it was postulated that the Jones-Ingold

mechanism applied, a sufficient quantity of the anipn of the

active methylene compolUld being furnished without recourse to

alkaline catalysts as a result of the comparitively high

dissociation constant of barbituric acid. It was found that

the reaction is second order kinetically and the rate depends

on the concentrations of barbituric anion and beta-nitrostyrene

12

in slightly acidic media. This kinetic study led to the mechanism

(Chart 6, Page 13) according to which rates and equilibria are

governed by a complex series of transformations.

According to this scheme, the barhi turate anion, the

concentration of which is governed by the total concentration

of barbituric acid and by the ionization constants K1 and K2 ,

would react in the rate determining step with p-nitrostyrene

to yield XIV, the adduct ionized at the position alpha to

the nitro group. A subsequent step in the mechanism would

involve a rapid protonation by IIA to give unionized adduct (XV)

or a rapid internal proton transfer to give more stable adduct

ani on (XVI) •

(10)

(11)

(12)

(13)

13

QlART 6

~AMLET AND GLOVER ~IECHANISM

H Buffer + A K-Buffer Buffer- + HA

NH - c = 0 Nil - C = 0 I K Barb. I I_

0 = c I 012 I

+A 0 = C 01 + HA I I I

NH - c • 0 NH - . C = 0

XIII

Nll - c • 0 I I -0 = c I

IH - Ol(Ph)-OI-N02 --!...

XII I + Ph - 01 = Oi - N02 _ b

a XIV + HA

b

a

NH - c = 0

XIV Nil - c = 0

0 = ! I

I II - QI(Ph) -CH2-N02+A

NH - c = 0

XV

Nil -I

c = 0

(14) XV + A .. 6

0 = c I_ +HA C - CH(Ph)-CH2-No2 I I

NH - c = 0

XVI

a (15) XIV ~ XVI

b

14

A systematic kinetic study of the normal Michael rmction

as applied to cyanoethylations of ethanolamine and acetyl

acetone catalysed by potassium hydroxide in aqueous media was

presented by Ogata, Okano, Faruya and Tabushi (33). The

mechanism (Chart 7) put forward by these workers agreed with

that predicted by the electronic theory which postulates that

the reaction would involve a nucleophilic attack on the beta-

carbon atom of acrylonitrile, the acceptor molecule (54).

CHART 7

Cyanoethylation of Ethanolamine

(Mobile)

(Slow)

(Fast)

In the course of studying the addition of haloacetates

and substituted haloacetates to Michae 1 acceptors under basic

conditions, ~·1cCoy (28) observed that these additions often

furnish the cyclic derivative_ , namely, the thermodynamically

less stable ~ cyclopropane dicarboxylates.

A recent kinetic study of the Michael Reaction of the

system-ethyl crotonate, dimethyl malonate, t-butyl alcohol

(solvent), and potassium tertiary butoxide (catalyst) was

15

undertaken by ~1ehta (31). He showed that the kinetics of the

normal Hichael roaction follO\'IS the expression:

d(aJduct) dt = kf( croton ate) {INll.onate anion) -kr(adduct anion),

which is consistent with the accepted ~lichael mechanism. Deter-

mination of the rate constants (kf and kr) necessi_tated an

improved mathematical treatment (translated into the language

of computer programming) which was complicated by the various

equilibria involved in the overall and concurrent processes of

the reaction.

In the absence of extensive kinetic data, several studies

have been made of the abnormal Michael reaction but there is no

common agreement in the literature regarding the true mechanism

leading to the rearranged products. However, the most widely

accepted theory on the mechanism of the abnormal Hichae 1 reaction

postulates that the formation of the abnormal adduct involves

the migration of a carbalkoxy group (41, 43, 44, 47). An

historical survey of the abnormal ~lichael reaction was made by

Shafer (42) and Korst (25) during their investigation of related

Michael reactions.

A kinetic investigation of the abnormal Michael reaction

between diethyl fumarate and diethyl ethyl-malonate, catalysed

by alkoxide, was made by Tsurata, Yashuara, and Farukawa (48(() for

the purpose of distinguishing between the Michael and Ross (48q:)

mechanism (Chart 8) and the llolden and Lapworth (16) mechanism

(Chart 9), neither of which has any justification based on

kinetics. As a mechanism for the abnormal Michael product

formation, Michae 1 and Ross (4&>) assumed the migration of the

methyl group of dimethyl mcthylmalonate to the alpha-carbon of

crotonic ester. Holden and Lapworth (16), however, suggested

that the primary addition product (XVII) might Wldergo Dieckmann

type condensation followed by decomposition of the cyclobutanone

(XVIII). Gardner and Rydon (12) studied the conditions necessary

for the formation of normal and abnormal products and formulated

empirical rules governing the conditions and structures necessary

for the various types of products. They examined both the above

mechanisms and concluded that the course of the addition reaction

is also affected markedly by the structures of the reactants.

TI1e conclusions drawn by these workers essentially agree with

the mechanism of Holden and Lapworth (16) and two rules were

formulated: · (1) Normal addition will always occur between

acceptors with no alpha substituent and unsubsti tuted addenda

16

such as malonic ester• (2) Abnormal addition will always occur

between acceptors with no alpha substituent and alkyl substituted

addenda. These rules can be considered to apply only in the cases

\'/here enough sodium cthoxide is present to bring about the

conversion to the abnormal product.

On the basis of their results, Tsurata, Yashuara and

Farukawa (48<) concluded that the Michael and Ross mechanism is

untenable because the total yield of product was constant with

time. Wulfman (52) proposed an alternate explanation by

17

CIIART 8

Nichael and Ross ~lechanisrn

fii3 Clli3 ~02Et

CH + llC C - Na II I I Cll

I HI - CH3 002Et

co2Et 002Et

OIART 9

Holden and Lapworth ~1echanisrn

CH3 002Et I C02Et Cll3

Cll I .· I I (19) II + CHR HC CR

CH I I I I C02Et QI C02Et C02Et 12

C02Et

XVII

Cll3 ;' R

-(EtOH) I I CH c - oo2Et

(20) 1 equivalent I I of Naoc2115 CII c

I II XVII m2Et 0

XVIIJ-

013 R (+EtOH) I I

(21) HC c ro2Et

I t

dccomposi tion H HC co2Et

~III I ro2Et

IXX

suggesting that the abnormal product could result from the

reversal of the normal adduct to the starting materials and

the subsequent slow reaction by the Michael and Ross nechanism,

which, he felt, was consistent with a constant total yield of

normal and abnormal adducts of variable composition.

18

Tsurata, Yashuara and Farukawa (4&\) intetpreted the Holden

and Lapworth mechanism as requiring the actual formation of the

non-ionized form. They concluded that the Holden and Lapworth

mechanism was inconsistent \dtb their observation that they

obtained a yield in excess of 60% of total adducts when operating

under conditions which prevented more than 60% stabilization of

the adduct anion being converted to non-ionized final product.

Wul fman (52) taking into account their data argued- that the

data was entirely consistent with the Holden and Lapworth

mechanism which requires that the abnormal adduct be in the

anion form in order to undergo Dieckmann type rearrangement via

a cyclobutanone intermediate to abnormal product.

The studies of Tsurata, Yashuara and Farukawa (~) indicated

that even though high c·atalyst concentrations, longer reaction

times, and higher temperatures have insignificant effect on

the total yield (detennined by distillation), they favor the

formation of the abnonnal products (determined from the linear

plot of the density against percentages of the normal products).

The experimental results of Tsurata, Yashuara and Farukawa

( 4&} led them to propose a new mechanism for the formation of

abnormal ~1ichael adducts. They proposed that the reaction

probably proceeds in two stages, i.e~, rapid formation of an

19

adduct anion (at the first step) stabilized by the successive

interaction with ethylmalonic ester or the slower isomerization to

the abnormal product at the second step.

The i'-lichael and Ross mechanism has been disproved by the

four isotopic studies (41, 43, 44, 47) which have shown beyond

any reasonable doubt that the abnormal Michael reaction involves

a carbalkoxyl migration.

Shafer (42), in an attempt to study the carbalkoxyl migration

in the abnormal Michael reaction, investigated the addition of

cyanoacetic acid and malonic esters to 3-rnethyl cyclohexanone

and demonstrated that only abnormal products are obtained from

these unsubstituted addenda when sodium ethoxide is used as the

catalyst. Shafer explained the carbalkoxy migration in the

abnormal Michael reaction by suggesting an alternative mechanism

(Chart 10) \vhich is consistent with the work of Tsurata, Yashuara

and Faruka\va ( 4&J but is no more supported by this work than

the Holden and Lapworth and the Michael and Ross mechanisms are

disproved (480.

Referring to Shafer's mechanism (Chart 10) for the related

Michael transformation, in the hindered system R = alkyl, a

carbanion (XXa) is formed by alkoxide addition to the acceptor

(11) in the presence of high alkoxide concentration. A Claisen

type condensation between the carbanion and a carbalko~yl group

of the addendum (XXI) may, by a concerted cleavage and displacerrent

reaction, give the abnormal product (XXIII). Alternatively, XXIII

20

CHART 10

Shafer's ·Mechanism

(22) CH 01 Cll3 l 3 I 3 I OI CHOC2H5 COOC2115 II -+ C2H50 I I CH HC: HC I I ,, c - oc2115 roc2H5 cF-> c - OC2H5 II " 0 0

II XX a XXb

OI C02C2HS R 13 I I CzHsO CH OIR

(23) XXa + CIIC02C2H5 I I I HC ~C2H5 1 c = 0 I . I co2c2115 o-OC2H5

XXI XXII a

(24)

XXII~

alternatively fH3 ~02C2HS OI-----CR + c2n5o-l I CH CO I <D2C2H5

could be produced by cyclization of the Holden and Lapworth

cyclobutanone intermediate. The mechanism does not require

the formation of highly strained cyclobutanone intermediate. It

offers an explanation for the formation of abnormal products

from unsubstituted addenda and is given additional support by

Michael and Ross (31).

The Shafer mechanism predicts that the rate of formation

of abnormal product (A) is dependent upon the acceptor and

addendum concentrations, whereas according to the Holden and

Lapworth mechanism the rate of formation of A is dependent upon

the concentration of the normal adduct (N). Wulfman (52),

therefore, suggested that by studying the rate of formation of

abnormal product - A from pure .N and from pure addendum and

acceptor, it might be possible to distinguish between the

alternative reaction paths.

The reaction sequence of the decomposition of a Michael

21

product to starting materials is, in accordance with the principle

of microscopic reversibility, the exact reversal of the accepted

mechanism for the Michael condensation (31). Patai, Weinstein

and Rappoport (31) studied the kinetics of the decomposition,

in methanol, of 4-nitrochalcone and malononitrile. They concluded

that the reaction belongs to the ElcB1 mechanistic class and the

rate-determining step involves unimolecular decomposition of the

conjugate base of the substrate, after ionization of a proton

from the at-carbon atom.

-----------------------------------1 Unimolecular elimination from a conjugate base.

22

The reversal of the ~1ichae 1 reaction studied by these

coworkers has a rather high activation energy (about 30 Kcal/mole)

1vhich accounts for a rate determining fission of a carbon-carbon

bond. ~luch lower activation energies \'lOuld be expected if the

rate determining step \oJere the ionization of a carbonic acid.

From the frequency factor of the reaction, !IS* was calculated

to be -13 e.u. \oJhich was found to be similar to the values

obtained for unimolecular eliminations from positively charged

ions. It was predicted therefore, that more solvation should

cause a small decrease in the rates.

Kaplan and Glover (22) investigated the kinetics of the

~lichae 1 reaction in nonalkaline media. In an aqueous dioxane

acetic acid - acetate buffer, the ~lichael addition of nitro

form (NF) to methyl acrylate (~leA) proceeded as in Chart 11.

The primary products of these reactions are methyl

4,4,4-trinitrobutyrate (r.teTNB), and a nitrite elimination

product, methyl 4,4-dintro 2-hydroxybutyrate (DNS). Depending

upon the specific reaction condition, MeTNB and DNS can tmdergo

further reaction leading to the formation of methyl 4 ,4-dini tro

-2-butenoate (DNU), and dimethyl 4,4-dinitro -2- hydroxypirnelate

(Cq) respectively. The reactions observed in the nitroforrn

methyl acrylate are depicted by the following equation;

NF

CHART 11

Addition of Ni troform to Methy1acry1ate

~leA

DNS · ·

C(N0 2) 3CH2Cll2co2cH3

MeTNB l-IIN02

-C(N02)iQI = CHC02 c113

DNU

23

24

; (25) NF + MeA ~An-

(26) An- + !lA ~ MeTNB + A-

(27) An---+ D:-JS + NOz

(28) DNS + l\teA ~cq-

(29) cq- + llA =.,Cq + A-

(30) ~lcTNB + Olr___..... DNU + No-2 , where

An- = C(N02) 3CH2CHCOzCH3 ;

cq- = CII2CHOHC02CJI3

" C(N02) 2 /

CH2l:Il C02 CH 3 , and

I lA and A arc buffer acid and its conjugate base.

The reaction forming MeTNB was found to be subject to general

acid catalysis and the mechanism involves a rapid and reversible

addition of trini tromethide ion to the double bond of methyl

acrylate follm-1ed by a rate determining protonation of the

resulting carbanion intermediate to form HeTNB. Kaplan and Glover

(22) compared k 1, the specific rate constant for the addition of

trinitromethide ion to lvleA forming the intermediate carbanion

1\.ii with specific rate constant for the addition of trinit-romethide v

ion to beta-nitrostyrene in methanol. Using the values of k 1 at

* * 35 ° C and 45° C, they calculated fill = 13.4 Kcal/mole and !IS = -28.9

cal/deg from the expression for the rate constant derived from

transition state theory.

The reaction forming DNS was found to compete for the

intermediate carbanion with the protonation of this intennediate

to HeTNB. The rate of formation of the OC-hydroxy ester is ~

kinetically first order in the intermediate carbanion and

inversely propotional to the acidity. The kinetic data and the

results of synthetic scale experiments in dioxane-112ol8 sup,gested

a cyclic transition state such as XXIV for the conversion of

M to DNS.

(31)

XXIV

Collapse of this transition state to products would occur

25

either by attack of a water molecule at the nitrogen atom (route a)

or at the o(-carbon atom (route b).- An al temate route (route c)

to the o(-hydroxy ester DNS would involve the collapse of the

transition state XXIV to the nitrile ester which would then

hydrolyse to DNS and nitrite.

Very recently, Abramovitch and Struble (1) reported the

first study of the stereochemistry of the Michael addition both

under conditions of kinetic and also of thermodynamic control

using a conformationally stable system - diethyl malonate,

4-:£_-butyl-1-cyanocyclohexane in the presence of sodium ethoxide and

ethanol, which permitted them to establish that the initial mode

of addition of the nucleophile involved a four centered transition

state. The kinetic evidence of the four membered cyclic transition

state for the Michael addition of diethyl malonate to methyl

croton1te in the presen~e of potassium tertiary butoxide and

!_-butyl alcohol was obtained prior to the publication of the

above work (53).

26

27

Chapter III

THEORY

Even though chemical kinetics may be considered as

fundamental a science as thermodynamics, the complexities are

such that the theory of chemical kinetics is difficult to apply

with accuracy. Because of the greater rigor of thermodynamic

methods, there has been considerable effort in the last thirty

years to approach kinetics from the thermodynamic point of

understanding microscopic phenomena in terms of atomic and

molecular structure and dynamics. The important feature of

this effort is the treatment of reaction rates as involving

equilibria between average molecules and high energy molecules

which are aligned and activated ready for reaction, or between

molecules in an initial state and in the so ·called "transition

state" or "activated complex". The thermodynamic formulation of

rate constants is based on the fact that the equilibrium bet,~een

reactants and activated complexes may be expressed in terms of

thermodynamic functions as well as by using partition functions (26).

One of the most significant conclusions to be drawn from

the theory of absolute reaction rates is related to the free

energy of activation (13). The useful form of the equation

arising from theory of absolute reaction rates in terms of the

If free energy of activation in the transition state, 6F is represented

by:

(32)

28

Since the factor (kT I h) is independant of the nature of the

reaction, it follows that the specific rate of any reaction is

determined by the free energy of activation at a given temperature,

In a direct extrapolation from thermodynamics, similar terms

can be derived for quantities such as 6S*, 6E*, Ml* and K•.

* . Of these terms, 6S often furnishes important information relating

to possible geometric configurations in the activated complex

relative to the ground state. The entropy can be considered as a

measurement of randomness of a system and the entropy of activation

is a measure of the freedom from restraint of motion in the

transition state (14). Since the activated complex can be treated

as a normal molecule with respect to its thermodynamic properties,

the entropy of activation is the standard entropy of the transition

state less the standard entropies of the reactants at the temperature

of the reaction. It may be positive or negative and reflects the

difference in the number and character of the translation~!,

rotational and vibrational degrees of freedom between transition

state and reactants as well as changes in charge distribution. For

reactions in solution, the entropy effects also include changes

in the randomness of the solvent molecules as new species requiring

differing degrees of sol vat ion are formed from the reactants.

The physical significance of the entropy of activation is explained

by the fact that every collision with the requisi.ts amotu1t of

energy does not necessarily lead to the formation of the activated

complex, and the probability of this formation is an essential

factor in determining the rate of reaction (SO).

29

The magnitude of the activation entropy often furnishes

valuable clues to the mechanism not otherwise indicated (51).

In general, a negative entropy of activation occurs in reactions

in which two molecules come together to form a single molecule of

activated complex (14). Highly negative entropies of activation

are also expected if a cyclic transition state is formed from

acyclic reactants, since rotation about the single h9nds becomes .

restricted during cyclization. Gaseous dimerizations, Diels-Alder

reactions and addition to double bonds are known to exhibit negative

entropies of activation (11, 26, 51).

For a reaction having a negative activation entropy, it

follo\vs, from the theory of entropy and probability, that the

more highly negative 65* is, the greater is the degree of

ordering in the transition state. A reaction may be slowed down

drastically by the necessity of passing through a highly ordered

(non-random) state.

It is to be anticipated that in many reactions the activated

state will resemble very closely the final state (49); in these

cases, the entropy of activation would not differ greatly from

the entropy change accompanying the overall reaction.

Determination of both energy of activation and entropy of

activation involves measurementof the temperature dependence of

the rate constant. The usual procedure is to plot (ln.k) against

(1/T) for a series of temperatures and to establish the best

straight line. Tite slope is equal to -Ea/R. With the activation

energy, Ea, established,the transition state theory defines the

following thermodynamic quantities for dilute solutions (14):

The free energy of activation, 6F*.

(33) 6F* = -RT lnK* = -RT ln [~~]

The heat of activation, Ml*.

(34)

(35)

6li* = -R d(lnK*) d (1/T)

= -R[d(lnk) + T] d(l/T)

The entropy of activation, 6S*.

6S* = +611* - 6F* T

= R(T d(lnk) dT + ln~- 1]

30

For any reversible reaction, the path of the reverse reaction

is exactly the reverse in all details of the path of the forlo~ard

reaction. This theory of microscopic reversibility when applied

to thermodynamics would lead to the conclusion that for any

reversible reaction, the activation entropy of the reverse

reaction is equal to the entropy of activation involved in the

forward reaction minus the entropy difference between reactants

and products. The principle of microscopic reversibility thus

often furnishes a valuable check as to which of a number of

species involved in pre-equilibria·steps, actually participates

in the rate determining step (R.D.S.).

31

Chapter IV

EXPERI~FNTAL

A. Purnosc of Investigation:

The l'lork of Wulfman (52) on the mechanism of the

abnormal Michael reaction suggested that the normal Michael

reaction is second order kinetically, and the rate is proportional

to the concentrations of the acceptor and the active form of the

addendum. The kinetic study of the normal Michael reaction

undertaken by Mehta (31) involved a direct extrapolation and

continuation of that work by using and expandin~ upon the

techniques developed by Wulfman (52). Mehta (31) studied the

normal Hichael reaction from the standpoint of base strength,

and acidity of the reactants, solvent and product, using dilute

solutions. The present work involves the s·tudy of the normal

~1ichael reaction from both the kinetic and thermodynamic view

points. All the kinetic data has been treated using the

~quation (20):

d(adduct) dt = kf (.malonate anion) (crotonate) - kt (adduct anion)

The forward and backward rate constants were determined using a

computer programed to obtain the best least-square fit of the

raw data and then determine these constants by iteration. Both

forl'f'ard and reverse activation energies and entropies of activation

were then determined by conventional methods (14). The thermodynamics ,.

of the reaction has been studied in order to propose a detailed and

more definitive mechanism of the nonnal ~fichael reaction from the

data obtained. An attempt is also made to explain the extent

of the reaction using the obtained thermodynamical quantities.

The principle of microscopic reversibility was applied in order

32

to test the validity of various acidities of the reaction components

as reported in the literature and several hypothesised intermediates.

B. Plan of Experimentation:

In th.is investigation the effect of temperature on the rate of

reaction was studied. The same concentrations of the react:mts,

base and sol vent were employed at different temperatures. A

Gas Cromatograph (GC) was used for the purpose of analysing the

reaction mixtures. Concentrations were determined using phenyl

cyclohexane as an internal standard.

The reaction of methyl crotonate, dicthyl malonate with

potassium tertiary butoxi<.le as base in tertiary butyl alcohol

\'las studied.

c. Experimental Set-Up:

Reactions were ~arried out in sealed ampoules. Since the

trial experiments showed that the half-life of the reaction was

greater than eight days at 30° C, the reactants could be premixed

in a volumetric flask; approximately equal volumes (3 rnl) of samples

were transferred to previously cleaned and dried ampoules with

the aid of a carefully dried 5 cc hypodennic syringe. These

tubes \oJere cooled and then seal~d. The zero time was taken as

the time when all the tubes were put into a constant temperature

oil or water bath. Temperature control of the bath was of the

order of + 0•2° c. The ampoules were withdra\m from the bath at

certain recorded intervals of time, cooled, opened and their

contents transferred to clean and moisture free small sample

tubes using a dry 2 cc hypodermic syringe.

D. Analytical Techniques:

33

In the present work, the analytical technique us.ed for studying

the system-methyl croton ate, diethyl malonate, potassium tertiary

butoxide, !_-butyl alcohol, 1-1-dicarbethoxy-3-carbomethoxy-2-JOOthyl

propane (product) and side products, was the quantitative estimation

of the components using gas-liquid partition chromatography. TI1is

technique also used and developed by Nulfman (52) and ~lehta (31),

pcrmi t ted the determination of changes in the con cent ration of

adduct with respect to time with an accuracy of better than two

percent.

1. Gas 01romatography (GC):

The gas chromatograph technique as developed by James

and :·lartin (19) for the analysis of fatty acids has found widespread

use in the petroleum, fats and oil industries as \'lell as a general

research tool by most organic chemists. It is essentially an

elution technique (3, 8, 23, 27, 32, 35, 37, 39) in which the

sample to be analysed is placed on a column consisting of a liquid

phase deposited on an inert solid support. The components are

differentially partitioned between the liquid phase and helium,

the carrier gas, and as a result the mixture is separated as it

34

percolates through the colunm.

The column used in this investigation was a six foot, 10 percent

silicone rubber, (Se 30) on 30-60 mesh firebrick, (Model 720U column

furnished by F & M Scientific Corporation, Avondale, Pennsylvania).

2, Operating Conditions:

Earlier work on the ~lichael reaction recorrunended the

following conditions under which the gas cromatograph. should be

operated to give the best resolution of peaks and still maintain

moderate retention times (31).

Detector temperature • • • • • • •

Injection port temperature • • • •

Oven temperature • • • • • • • • •

Current. • • • • . ' ' . • • • • •

• • • 3so "c

• • • 300 °C

170 °C • • •

• • • 150 milliampere D. C.

Helium flow rate 0 • • • • • • • • • 0 • 86-90 cc per minute

The above operating conditions were also used in the present

investigation.

3. Sampling:

Two to three mic~o!iters of the sample to be analysed

was introduced into the column using a ten microliter hypodermic

syringe.

E. Preparation of Calibration Curve:

Phenyl cyclohexane was used as an internal standard for the

purpose of calibrating the equipment. Several samples prepared

from known amounts of the standard and adduct were analysed by

35

gas chromatography and the area mder the adduct peaks and standard

peaks were measured (52). A plot of area ratio of adduct to

standard against mole ratio of the adduct to standard was prepared

as in Fig. 1, Page 36 • This technique is discussed in reference

(23) on gas chromatography.

F. Exnerimentation:

The mixture of methyl crotonate and diethyl malonate was

allowed to react under the influence of potassium t-butoxide in

!_-butyl alcohol at different temperatures and using the sealed

ampoule technique described before. The reaction time of one

hundred and ten hours was arbitrarily chosen for each rm.

Initially, at small intervals of time and later at longer

intervals of time, samples were taken out of the ampoules, after

cooling and opening them, using a two cc dry and clean hypodermic

syringe. The samples were treated with several drops of O.lN HCl

to arrest further reaction and a small amount of potassium carbonate

was added to dry the samples and remove any excess acid. The

samples were centrifuged for at least tNO minutes, the liquid

was removed by decantation, placed in numbered vials and saved

in an ice box for later analysis by gas chromatography.

G. Data and Results:

Experimental data for the various runs made are listed in

Tables II to VI. Results of the experiments are summed up in

Tables VII and VIII. Appendix A consists of general programs for

the sample cal~ulations of:

36

1.0

o.s

!-:c ~~~ u :-o .21@ ~~~ 0.6 <t·V')

' t;...; !-...... 0 0

c:;: C'CI (l) e $-<

<t < 0.4

~~~

0.2

o.o 0.2 0.4 0.6 . 0.8 1.0

~Ia ~1olcs of Adduct MS ~1oles of Standard

Figure 1. Standard Gurve of Area-Ratio as a Function of Mole-~atio.

37

1. The con cent ration of adduct (Page 70).

2. The rate constants (Page 71).

3.. The energies of activation (Page .73). ·

In all the five runs that were made, the following quantities

of reactants, base internal standard and solvent were utilized:

~\'eight of methyl crotonate = s.o + 0.001 grns.

Weight of diethyl malonate = 12.8 + • 001 gms.

Weight of phenyl cyclohexane = 9.6 + .001 gms.

Volume of 0.106N t-Butoxide = 4 ml.

(in the final volume of the mixture = 100 ml.)

38

TABLE II

Experimental Data for Run 1 Reaction Temperature = 30°C + .2°C - .

c..

Sample Time, Area of Adduct Adduct-Cone. No. Hours Area of Standard ~foles/liter

1 5 0.1350 0.0954

2 10 0.2000 0.1413

3 15 0.2500 0.1766

4 20 0.2950 o. 2084

5 25 0.3150 0.2225

6 30 0.3250 0.2295

7 35 0.3400 0.2401

8 40 o. 3500 0.24 72

9 50 o. 3650 o. 25 78

10 60 o. 3680 0.2599

11 70 0.3700 0.2613

12 80 o. 3750 0.2649

13 90 o. 3850 0.2719

14 100 0.3900 o. 2755

15 110 0. 395 0 0.2790

Sample No.

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

TABLE II I

Experimental Data for Run 2 Reaction Temperature = 40° ~ ,2°C

Time, Hours

5

10

15

20

25

30

35

40

50

60

70

80

90

100

110

Area of Adduct Area of Standard

0.14 70

0.2140

0,2640

0.3060

0,3280

0.3390

0.3540

0.3640

0.3800

o. 3850

0.3860

0.3915

0.3990

0.4040

0.4100

Adduct-Cone. Moles/liter·

0,1038

0,1511

0,1865

0.2161

0,2317

0,2394

o. 2500

0.2571

0. 2684

0,2719

0,2726

0.2 765

o. 2818

0.2853

0.2896

39

Sample No.

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

TABLE IV

Exnerimental Data for Run 3 Reaction Temperature = 60° ~ .2°C

Tire, Hours

5

10

15

20

25

27

30

35

42

so

60

71

80

90

100

110


0.1780

0.2400

0.2900

0.3330

0.3550

0.3344

o. 3675

0.3800

o. 3925

0.4100

0.4140

0.4225

o. 4275

o. 4285

0.4325

0.4370

Adduct-Cone. Moles/liter

0.1257

0.1695

0.2048

0.2352

o. 2507

0.2362

0.2596

o. 2684

0. 2 772

0.2896

0.2924

0.2984

0.3019

0.3026

0.3055

0.3087

40

Sample No.

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

TABLE V

Experimental Data for Run 4 Reaction Temperature = 70° _:: .2°C

Time, Hours

5

10

15

20

25

30

34

40

50

60

70

80

89

100

110


0.2080

o. 2530

0.3030

o. 3450

o. 3680

0.3820

0.3930

0.4070

o. 4250

0.4290

0.4330

0.4380

o. 4440

0.4470

0.4510


0.1469

0.1787

0.2140

0.2437

0.2599

0.2698

0.2776

o. 2875

0.3002

0.3030

0.3058

0.3094

o. 3136

o. 315 7

o. 3185

41

Sar.1ple No.

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

TABLE VI

Experimental Data for Run 5 Reaction Temperature = 90° .:!:. .2°C

Time, Hours

5

7

10

18

20

25

30

35

40

45

50

60

70

80

90

100

109


0.2100

0.2419

0.2800

o. 3499

0.3700

0.3950

0.4100

0.4200

o. 4350

0.4467

o. 4550

0.4600

0.4650

0.4700

0.4720

o. 4 750

0.4790


0.1483

0.1709

0.1978

o. 24 71

0.2613

0.2790

0.2896

0.2966

o. 3072

0.3155

0.3214

o. 3249

0.3284

0.3320

0.3334

0.3355

0.3383

42

.. ..., u ::l "0

~ tH 0

o.-3o

0.25

0.20

.::: 0.15 0

•P'I ..., CIS $-4 ..., c:: 8 6 u 0.10

o.os

Run 1. Reaction Temperature = 30°+0.2°C

20 40 60 80 100 120

Time, Hours

Figure 2. Concentration of Adduct as a Function of Time.

0.25

...

0.20 Run 2. Reaction Temperature = 40°+0.2°C

0.15

0.10 20 40 60 80 100 120

Time, liours


o:3s· ---.---, -l r -- , • ,-. ---, ·-.-·

0.30

0.25


0.20

0.15

('

20 40 60 80 100 120

Time, Hours


o;3s

0.30

._; u :l ""::) o. 25 :i

0.20

o.1s·

0.10


20 40 60 80 100 120

Time , llou rs

Figure s. Concentration of Adduct as a Function of Time.

h o. 30

a> ..., ·~ ..... .......... Ill a> ..... 0 :2 0.25 .. ..., 0 :l

" Rtm s. Reaction Temperature = 90°+0.2°C " < ~ 0

c:.:: 0

0.20 ·~ ~ C'CI ... ..., s:: a> 0 c:.:: 0 0.15 u

o.lo 20 40 60 80 100 120

Time • Hours


Chapter V

DISCUSSION

A. Discussion of Data and Results:

In investigating the kinetics of the addition of diethyl

48

malonate to methyl crotonate in t-butyl alcohol, catalyzed by

potassium tertiary butoxide, five runs were made with the same

concentrations of reactants and base but at different temperatures.

The data of Run& 1 to 5 are listed in Tables II to VI, Pages 38 to 42,

The adduct concentrations \iere evaluated using a computer program

(Appendix A, Page 70). The data were treated by the least square

method, using the sp~cial program (+ + XEQSQ-IPLS) stored in the

computer center of U.N. R., to evaluate a relation between adduct

concentration and time (Plots 2, 3, 4, 5 and 6 on Pages 43 to 47).

The least square treated data best fitted a fourth degree poly

r.ominal within about 1-2% error at 95% confidence level. From

the least square coefficients, forward and backward rate

constants and the equilibrium constant were calculated using a

general computer program (Appendix A, Page 70). Table VII, Page 49

shows the. dependence of these rate constants on temperature.

The results of Table VII indicate that with the exception of the

for\iard rate constant evaluated at 70°C, the forward rate constants

increased \iith temperature while the backward rate constants decreased

with increasing temperatures and the equilibrium constant was

found to increase as the temperature was increased. Based on

the reported value of the equilibrium yield of 65\ at 100°C,

TABLE VII

De?cndence of Rate Constants on Temperature*

Ter.1pcrature** . kf 0 C Liter · r·1ole s lr,lin. -1

30 6.122 612.1

40 6. 326 579.6

60 6.514 512.0

70 6.304 460.1

90 7.007 446.3

K*** ~ e = v • ·r

0.80

0.87

1.02

1.10

1.26

*The rate constants were calculated using the following values

of t :te ionization constants:

Km of malonate = 1.6 x 1o·l8

Ka of adduct = 2.0 x lo-12

Kb of tertiary butyl alcohol s 1.0 x lo-19

**All the temperatures are within .t o. 2°C

***Kc stands for equilibrium constant which takes into account

the ionization constant values of malonate and adduct.

49

TABLE VIII

Equilibrium Yields at Various Reaction Temperatures

Temperature* a· . c

30

40

60

70

90

*Measured up to ~ 0.2°C.

% Yield of the Product at Equilibrium **

58,3

59,6

62,0

63.1

64.9

**Based on the reported value of the equilibrium yield of

50

the equilibrium yields of the adduct at various temperatures

were evaluated and are presented in Table VIII (Page SO). It

is clear from both Table VII (Page 49) and Table VIII (Par.eso )

that the reaction under investigation is not sensitive to

tel11?erature variations.

51

The activation energies and entropies of activation (Table IX,

Page 52) were determined by conventional methods disc:ussed in

01apter II I.

B. Discussion of Hichael l\lechanism:

Kinetic studies of the system-methyl crotonate, diethyl

malonate 1 !_-butyl alcohol and potassium tertiary butoxide are

con!listcnt with the generally accepted Hichael mechanism

(Owrt 4 1 Page 10). llmvcver, an examination of the transition

state (Table IX, Page sz) indicates that the entropy of

activation is one of the most negative known. l'lhen compared

with those of a number of well studied reactions (Table X,

Page sil, it becomes difficult to account for the value obtained

except by suggesting a cyclic mechanism (Chart 12, Page 54 ) •

ror the addition of diethyl malonate (I, X = COOC2115 ) in

t-butyl alccoi<ol catalyzed by potassium tertiary butoxide, a

highly negative entropy of activation appears to be consistent

with a mechanism involving a cyclic intermediate such as XXVI

or XXVI I which can collapse to the more classical intermediate

XXVIII and then become protonated to furnish XXIX. A possible

test of cyclic hypothesis was reported by McCoy (28) who observed

52

TABLE IX

Activation Parameters

= 4 73.7 cr.l/mole*

Ear -1167.4 cal/mole*

T t:.P cal t:.H* ~ t:.s* mole mole '

e. u. Temperature,

if * " t:.II" t:.S « t:.S" oK t:.F f t:.F r t:.H f r . f r

303 + 0.2 16,654 13,881 -128 -1769 -55.4 -51.7

313 + 0.2 l 7,203 14,394 -148 -1789 -55.4 -51.7

333 + 0.2 18,324 15,437 -188 -1829 -55.6 -51.9

363 + o. 2 19,985 16,989 -248 -1889 -55.7 -52.0

*Evaluated from the slope of (lnk) vs (1/T).

53

TABLE X

Activation Entropies of Some Well Studied Reactions

Reaction 6S = f(solvent), e.u.

1. Oiel-Alder Reaction (33) 2Csli6 ~ c10H12

2. Menschutkin Reaction (33) A. (C2H5 ) 3N + c2H5 I -(C2H5 ) 4N+I-

B. c2H5N + CH3I- C2H5N+OI3+I-

+ - +

C6II5COCII2Br =" Br-

o. c2H5N + CH3 I __.,. (C2H5 ) 3N+cH3+ r-

3. Reaction between Ions (33)

-38 to-47

-29 to -35

-34 to -61

-34 to -41

S204 = + S204 = __. S205 = + S203 = -41

4. Moderately dispersed charge in T.S. (46) CH3I + r•-- CH3I * + I- (in acetone) -49

s. :Vlichael Reaction in non-alkaline media. (22) -C(N02) 3 + CH2 = CliC020I3 __ ...,

-28.9

54

C!IJ\RT 12

Hodi fication Cif the General r.ti chael Mechanism

COOC2H5 I n-

(36) CH I 2 HB X

I

0 OCH3

"/ c I

(37) c - R3 +

II II OR

c ~

l\2 Rl XXVI

Cli302C o-I I

n.3 - c c - OC2115 I I ...

n.2 - c - C- X

~1 I H XXVII I XXVIII a

XXVIIIa or XXVIII or XXVI

XXVI lib

(38) XXVII I a

XXVII Ib

co 2CII3 ..illL. I 3 1r'- II-C-R

2 I R -C- Rl

I 11-C-X XXIX

\ COzCzHs

55

that ~1ichael additions of carbanion XXV (X = e1, R = alkyl or H)

frequently furnishes the therroodynamically less stable cis

cyclopropane dicarboxylates. It would now appear that these

compou,1ds resulted from a concerted collapse of the intermediate

XXVI (X = ~1) or perhaps XXVII (X,. fl) with loss of chloride ion.

The choice bet\'leen transition states similar to XXVI :_

(6 membered) or XXVII (4 membered) is not easily made.. Ilowever,

a six membered transition state is inconsistent \'lith cyclic

ketones undergoing ~1ichael reactions, if we assume the mechanism

is the same in cyclic and acyclic cases. The six membered

transition state can be rejected on the ground that it requires

the physically impossible S-cis configuration as in the dimerization

of methyl vinyl ketone and crotonaldehyde to furnish dihydropyrones

(53). The four membered intermediate, on the other hand, allo,.,.s

for the inclusion of Michael reactions involving cyclic and

acyclic acceptors using a single mechanism. The existance

of this type of transition state is supported by the reaction of

ketene acetals with unsaturated carbonyl compounds to furnish

cyclobutanone ketals (29). Some possible four membered transition

states are indicated in Q1art 13 (Page 56). Korst's (25)

observation that the ~!ichael adduct of diethyl malonate and

tertiary-butyl croton ate upon mild acid hydrolysis loses approximately

one half of one carboxyl group as carbon dioxide, strongly suggests

that the crotonate-malonate system does pass through a symmetrical

~ransition state such as XXVII.

56

CHART 13

Some Possible Four-Membered Transition States

~o2;.1e 0 ~o2Me 0 - I I

IIc::::-=--c c- OEt uc::=-c C-OEt cis I I I I

IIIIJIIIIC ~-== COzEt H 111111C C -=::::::1 H ~· - ~ I CII3 II CII3 cq2Et

~o2~1e o- ~o2Me 0 I - I

11 [/'C C --OEt ll t::::... c C-OEt t rnns I I I I

CII3111J C ~ oc::::::l CO2 E t CH3 1111C C....:=H

~ = A I II I{ H C02Et

a-Additional states would result when C <::" is replaced

<OEt "-.OEt by C in the above models.

07"

57

llaving differentiated bet,.,reen the six and four membered

transition states, we suggest that the mechanism of the Michael

reaction studied can be depicted as shown in Chart 14.

CHART 14

Cyclic Hypothesis of Hichael Reaction

This mechanism predicts the formation of two products via paths a

and b, which are (for intents to be discussed in Part D of this

chapter) identical. Path a furnishes a "normal" (R = ll) and

path b furnishes an "abnormal" (R is other than II) rvtichael product.

The work of r.tcCoy (28) with substituted chloroacetates which

furnish both cis and ~ cyclopropane dicarboxylic esters is

also consistent with the proposed mechanism (Chart 15).

mtc o-\/

c ll +

/c\ R Cl

CHART 15

Interpretation of McCoy's Work

R Cll 3 co2r.-~

y co2r-te

58

Due to the planarity of both reacting species the steric requirements

are considerably less than those involved in SN2 type process and

it is more reasonable to expect the presence of both cis and trans

diesters.

The pro;_)Oscd mechanism (01art .14) is directly analogous to

the unsaturated carbonyl COJn?ounds to furnish cyclobutanone

ketal~(29) (Chart 1~).

CHART 16

AdJi tion of Ketene Acetals to Unsaturated Carbonyl Compounds

CHCOR + CII2 = C (OC2H5) 2

C6HS Ill- TICOR

CII2- C (OC2II5 ) 2

l{;II5CIICH2COR .. . ~ ..

• Cli2COOH

This J:-tcchanism also accounts for the possibility of the product

anion being XXVIIIb since it is an easy matter for a proton to

undcr~o a 1-3 shift in the envisaged transition state.

c. Si gnificance of the Rate Constants for the Reverse Process

and of the Principle of Microscopic Reversibility;

The distinction between which of the adduct anions XXVIIIa

and XXVIIIb in Chart 12 (Page 54) is involved in the R.D.S. can

be realized by applying the principle of microscopic reversibility

and also by observing the magnitudes of first-order rate constant

for the reverse process. Of several values listed in the

59

literature for the ionization constants of the reaction components,

the ionization constants for methyl malonic ester and ethyl

propionate offer fair models for the conjugate acids of XXVIIIa

and XXVIIIb (34).

The approximate acidities of the reaction components

presented (Table XI, Page 60) are adopted from, or estimated by,

using data available from several sources (5, 17, 34).

Table XII on Page 60 represents the values of kf, kr, ~

constants and ~~S*(=~sr - ~S~) calculated at 30°C using different

combinations of ionization constants of adduct and malonic ester.

Certain combinations of ionization constant values can immediately

be excluded because the resulting entropy difference between forward

and reverse processes (~~S*)2 violate the principle of microscopic

reversibility, or result in first-order rate constants for the

reverse p,rocesses that are of a higher frequency than molecul~r

vibrations.

Clearly if one uses the values offered by Model XXVIIIa in

Table XII (Page 60), the intermediate XXVIIIa is not permissible

due to the necessity of kr being so large and the extreme differences

between the entropies of activation. The rate constants for the

reverse of XXVIII are extremely large and within a power of two

of the value for the rate of ionization of methyl malonic ester

in water and probably exceeds the rate of this process. in tertiary

butyl ;~ l cohol.

If one assumes that the maximum difference between the forward

and reverse activation processes should be 4S for the reaction and

------------------------------------2. ~~S* ; AS -reaction.

60

TABLE XI

Acidities of Reaction Components

Co:::ponent pKa

CII (COOC H ) 2 2 5 2

13 (17) 17.79(34) 13.30 (5)

R-CII (COOCll3) 2 15 19.70 14.70

R1-CII(COOCII3) 2 26 25.69

(CH3) 3COH 19 19.00

CH3CII = CIICOOCH2CH3 14

R = CH31IICII2 COOCH2 CIJ3 Rl = CH31HCII(COOCH3) 2

TABLE XII

Rate Constants and Entropies of Activation as Functions of Ionization Constants

iVIode 1 * Ka Km :~ kr Keq 6/:J.S*=t:J.S* f-l:J.S' r

XXVIIIb 2 x 1o-20 1.6 x 1o-18 6.122 612.1 0.80 3.73

XXVIII a 2 X 10-26 1.6 X 10-18 1.061 X 102 611.4 X 106 0.80 31.18

XXVI lib 1 x 1o-15 5 X 10-14 3.737 235.5 o. 79 3.85

XXVI II a 1 X 10-26 5 x 1o- 14 3. 724 234,8 X 1011 0.79 53.18

XXVI II a 1 x lo- 26 l X 10-13 3. 724 469.6 X 1011 o. 79 54.45

XXVIIIb 2 x lo-15 1.6 X 10-13 3. 732 376.4 0.79 3.78

*Refer to Chart 1.2, Page 54.

proceeds to calculate this value on the basis of (1) changes in

degrees of freedom and the entropy of mixing, and (2) thermo

dynamical data for the model trans 2-butene + propane ------~

2,3 dimethyl pentane (~lodel A) or propylene + n-butane

61

2,3 dimethyl pentane (:vlodel B). the results presented in Table XIII

are obtained. An examination of the values of 6S obtained by

various methods shows that they are in fairly good agreement

with the experimental value of t:S • Thus all data and results

support the intermediate being XXVIIIb and not XXVIIIa. This is

further supported by the cyclic transition state, since it simply

requires a concerted 1,3 hydrogen shift in the transition state

(either four membered or six membered). The existnnce of the

four membered transition state is supported by the addition

of ketene acetals to tmsaturated carbonyl compotmds to furnish

cyclobutanone ketals (29), and is favored due to the fact that

intermediate XXV is a ketene hemiketalate.

D. Objections (Reservations):

·n1c proposed mechanism for the typical ~1iahael reaction

(Chart L4, Page 57 ) , based on the results of the present investigation,

suggests that both normal and abnormal Michae 1 reactions proceed

along ne arly identical reaction paths. Referring to Chart 14::

(Page 57), when the substituent Ron carbon 1 is hydrogen, the

normal r-.tichael reaction follows path a; and if R happens to be

different than II, path b leads to the formation of the abnormal

Michael adduct. Hence the normal as well as the abnormal Michael

adduct presumably passes through similar transition states.

TABLE XIII

Theoretical Values for AS-Reaction

;,let hod

(1) Statistical -4.4

(2) The rmodyn ami cal

A. Unnormalized ~to del A -20,1*

B. Unnormalized Model B -20,4*

c. Normalization to ethylene of

~1odel A -3.3

Model B -11.4

*Does not account for the fact that the stabilization energy

associated with a c=c double bond in methyl crotonate is of

the order of zero kcal calories whereas for trans 2-butene it

is 5.2 kcal, and for propylene it is 2.7 kcal.

62

' 63

\'/hen the aforementioned hypothesis is examined in light of

the most plausible abnormal Michael mechanisms, it becomes clear

that the proposed mechanism explains the formation of the normal

and abnormal products ~ two independent reaction paths. The

work of Holden and Lapworth (16) and of Shafer (42) on the

abnormal Michael reaction has been reviewed in Chapter II.

The llolden-Lapworth (16) theory assumes the normal adpuct as a

precursor of the :-·lmormal. Their mechanism may be represented

by the following sequence of reactions.

He - CII - CHz <DOEt I

R - C - <DOEt I COOEt

~ie - rn - ffiCOOEt I I

R- c -co I OOOEt

~ Me - CH - CHCOOEt

' R- CH I COOEt

Shafer's (42) mechanism (Chart 10, Page 20) of the abnormal Hichael

Reaction does not presume the normal adduct as a precussor of the

abnormal, but offers an explanation of the abnormal product from

unsubstituted addenda, possibly !!2 a cyclobutanone intermediate

\-.rhich is identical to that proposed by Holden and Lapworth (16).

Both tho above mechanisms as '"ell as the mechanism presently

proposed, as a result of this investigation, support the existance

of a four membered cyclic intermediate. Moreover, in contrast to

the mechanisms of Holden-Lapworth(l6) and Shafer(42), the present

mechanisra explains the formation of normal and abnormal adducts

64

via independent reaction paths which are alnost identical.

Similar though not identical, transition states would be involved

in the normal and abnormal Michael reactions. If could be further

assumed that the transition state of the normal Michael reaction

is one of the possible states indicated in Chart 13, Page 56,

whereas the abnormal adduct passes through another one of these

eight possible transition states. However, the abnormal transition

state requires more activation energy than the normal transition

state in the forward process (i.e. it is thermodynamically less

stable than that of the normal adduct). The abnormal product is

thermodynamically more stable than the normal adduct and the reverse

process for the abnormal product to starting materials is less

favorable. A correllary of this is that retrogression is favored

over simple reversal. As the base concentration is increased,

there is more possibility of the abnormal Michael product formation

because the reaction proceeds through the transition state more

often. This allows a greater opporttmity for the abnormal

transition state to be reached.

The abnormal Michael product is not known to be formed in

all the ~lichael reactions. The reaction of ethyl crotonate

with diethyl malonate did not seem to form the abnormal adduct in

heterogeneous media. The explanation of this is not obvious.

However, before the present mechanistic generalization could _be

applied to this reaction, it would be fruitful if the reaction is

repeated in ~-butyl alcohol which would form a homogeneous medium

for the reaction.

Korst (25) has found the abnormal addition to occur between

tHo unsubstituted reacting species, t-butyl crotonate and diethyl

malonate, in ~-butyl alcohol (solvent) and potassium tertiary

butoxide (catalyst). This is consistent with the proposed

mechanistic generalization (Chart lJ, Page- 5'7). However, the

method of analysis and results probably requires verification.

65

66

Chapter VI

WNCLUSIONS

The study of the typical ~tichael Reaction described in this

thesis leads to the follO\'Iing specific conclusions.

A. The forward reaction is endothermic and is very

insensitive to temperature.

B. The activation energy for the forward and backward

processes is 473,7 and pll67,4 cal/mole respectively.

c. The entropy of activation (6S*f = -ss. 7 e.u. at 90°C)

is one of the most negative known and is only consistent with a

cyclic transition state. The four membered transition state is

more consistent with the general scope of the Michael Reaction.

D. The observed values of 6S * and kr are realistic only

if the adduct anion involved in the reverse process is

COzMe I cii2 I

illzEt I_

CH c I I 013 ro2Et

which is not the classically accepted species

co2Me I

-CH cn2Et I I Cll CH

I I CH3 C02Et

E. The normal and abnormal Michael Reactions proceed

through similar but not identical transition states.

F. A large amount of work is needed to relate all existing

data with the proposed mechanistic path.

67

Chapter VII

SU~1ARY

A typical Michael reaction has been investigated from the

kinetics and the thermodynamic view points. Temperature effects

on the rate of this reaction are reported, and the evidence

presented indicates that the transition state in such Michael

reactions is probably cyclic. The intermediate anion involved

in the reverse process is very likely different from that

classically accepted.

On the basis of the ~xperimental results, a new mechanism is

68

proposeJ, which, in contrast to other Michael mechanisms, explains

the formation of normal and abnormal Michael adducts via independent

but similar paths.

The proposed mechanism assumes a 1, 2 addition of the addendum

anion in the form of a ketene hemi acetate to the acceptor to form

a hemiketalateof a cyclobutanone followed by subsequent collapse

to products. The use of substituted chloroacetates as addenda

offers a possible means of trapping the : intermediate. Evidence

of the four centered transition state in the Hichael addition of

diethyl malonate to 4-.!_-butyl-1-c:yanocyclohoxane in the presence

of sodi urn cthoxide and ethano 1 has been recently reported by

Abramovitch and Struble ( 1). The proposed mechanism can accotmt

for the observed results in these experiments and is consistent ... _,__

\vith those reported here. A large amount of work is needed to

determine the extent to which the proposed mechanistic generalization

can be applied to various Michael reactions.

69

APPENDICES

70

APPENDIX A

LIST OF Cm1PtrrER PROGRAMS

Program for the Calculations of Adduct-Concentrations

C CALCULATION FOR ADDUCT CONCENTRATION, USING CALIBRATION CURVE DIMENSION TIME(35),ARASH(35)rAOH(35) PRINT 00 PRINT 101 PRINT 102

------~R~EAD 1,_~~~,_~0~~W~S~,~S~L~O~P~E~----------------------------------------READ 2dTIME(I),ARASH(II,I=lrN) CS=(GS/W$)*(1000./VOL) . DO 3 K=1 N RASHN=SLOPE*ARASH(K)

3 ADH(K)=RASHN*CS ------~P~INT 103 1 (TIME(l),ARASH(J),AOH(I),I=l 1 N)

PRINT 101 PRINT 105

100 FORMAT(8X,l6HTEMPERATURE=30 C) 101 FORMAT( I) 102 FORMAT ( 8X, lOHTI ME ,HOURS, BX, 10HAREA RATIO tBX, 18HAODUCT-GONC • ,MOL/L) 103 FORMAT(3Fl8.4) 105 FORMAT(6X,35HUSE THE SAME PROGRAM FOR OTHER RUNS)

1 FORMAT(I2,4E14.8) 2 FORMAT(6F12.4)

STOP END

TEMPERATURE=30 C

TIME,HOURS AREA RATIO AooUCT-CON~.,MOL/L 5.0000 .1350 .0954

10.0000 .2000 .1413 15.000~0~-----------~·~2~5~0~0~----------~·~1~7~676-· ______________ ___

----------:20 .(fOOO • 2950 .2084 25.0000 .3150 .2225 30.0000 .3250 ·i295 35.0000 .3400 .2401 40.0000 .3500 .2472 5o.oo.o~~o ____________ ~·~3~6-~5~o----\ ~------~·~2~5~7~8~-----------------6o.oooo .3680 .2599 70.0000 .3700 .2613 80.0000 .3750 .2649 90.0000 .3850 .2719

100.0000 .3900 .2755 110.0000 .3950 .2790

USE THE SAME PROGRAM FOR OTHER. RUNS

STOP END Of PROGRAM AT STATEMENT 0002 + 01 LINES.

A Program for the Calculations of Rate and

Equilibrium Constants

C CALCULATIONS FOR RATE-cONSTANTS ------~DIMENSION T(95),X(95),Y(95),81(95)

PRINT 100 PRINT 101 PRINT 103

71

--------PRINT--101----------------------------------~----------------

PRINT 102 READ 1,AKB,AKA,AKM . READ 2,VOL,WMH,WC,WS,OC,OHH,OS,WT8,ot8,t8,Gt,GMH,GS,V~ READ 3,N . READ 400, (Bl( I) ,1=1,5)

c,....--F I R-sr--oArA-s"A...-O"Ur-L --o-a.n--E -A,.--.Zor-.E...-.Ror.O..--.V,AI"Tl-ru .... E..-------------------T(1)=0.0 A=GC/WC*1000./VOL B=GMH/WMH*lOOO./VOL CS=GS/WS*lOOO./VOL C=CB*VB/VOL VTB=VOL-VB-GC/DC-GMH/OMH-GS/OS BH=VTB*DTB/CVOL*WTB)*lOOO.O L=N+l DO 21 I=l,L Q=Bl(5)*(T(I )**4) X(l)=Bl(l)+Bl(2)*TCI)+Bl(3)*(T(l)**2)+81(4)*(T(l)**3)+Q

21 T(I+l)=T(I)+lO. DO 22 I=l,N DELX=X ( I+l )-X (I) DELT=T(I+l)-T(l)

22 Y(I)=DELX/DELT Cl=O.O

2=0.0 C3=0.0 C4=0.0 C5=0.0 · DO 33 I=l,N XM=(X(l)+X(l+l))/2.0

----p-RT =AKW#l B-XM) +AKA*XH+AK8*8A ·P=(A-XM)*(B-XM) Zl=P/PHI Z2=XM/PAI Cl=Cl+Y(I >*Zl C2=C2+Zl*Zl C3=C3+ZI*Z2 C4=C4+Y (I) *Z2

33 C5=C5+Z2*Z2 Al=<C3*C4-cl*C5>7Ic3*Ci=tz•c5) A2=CAl*C2-ClJ/C3

~

AKl=Al/(AKM*C) AK2= A2/ ( AKA*C) AKBL=(AKl*AKM)/(AK2*AKA) PRINT 104,AKl,AK2,AKBL PRINT 101

72

----PRTwr-l-05;--------------.,..---------------100 FORMAT (6X,l6HTEMPERATURE•30 CJ 101 FORMAT ( /) 102 FORMAT (6X,9HK-FORWARo,7x,IoAK-BACRHARo,7x,13RR-EOOIL18RI0R) 103 FORMAT(6X,l8HK-MALONATE=l.6E-18,5X,l6HK-AOOUCTa2.0E-20) 104 FORMAT(5X,F9.4,8X,F9.4,lOX,F6.2)

----..-1~5i=DR}fAT ( 6X, 35RUSE THE SAME PROGRAM FOR OTHER RUNS J 1 FORMAT (3El8.8) 2 FORMAT (6Fl2.4) 3 FORMAT(l2)

400 FORMAT (4El8.8) STOP

------~END~------------------------------------------

TE1"1PERATURE=30 C

K-MALONATE=le6E-18 K-A OOUC Ta2 • OE-20

K-FORWARO 6.1224

K-8ACKWARD 612.0693

R-EOOILIBRIOH .eo

USE THE SAME PROGRAM FOR OTHER RUNS

STOP END OF PROGRAM AT STATEMENT 0400 + 01 LINES.

\

73

A Program for the Calculations of Activation Energies

-:' _ I S T ? !', HIT E P, ~~~~--------------------------------------------------------:;; ;, L L : ; 'f /', -,- ; : I' i c : .. ! "( i· II-\ :J

C C***216lJCN461W. SHETH R P 03/01/66 FORTRAN 2 0030 002 0 r:. Ct'.LCUL12.TIOI'-iS FOR t\CTIVATII1i'J EI~ERGIES

DI~ENSION nFF(lOl,DFB(lO),DHF(lO),OHB(lO),DSF(lO),OSB(lO) D I ,' 1 E i·l S I 0 i'l T ( 10 ) , r= K ( 10 ) t B K ( 10 ) , F K P ( 1 0 ) , B K P ( 10 ) , T P ( 1 0 ) RF AD 7, .~1 Rf:1\D b,R,PK,CK r~ F AD 3 0 0 , ( T ( I ) , F I< ( I ) , B K ( I ) , I = 1 , N ) PI~ Ii'!T lOR DO 1 I= 1, •"I 3 I< P ( I ) = L 0 G F ( B K ( I ) ) r= I< P ( I ) = L 0 GF ( F K ( I ) )

1 TP(Il=l./T(I) . Xf\=(TP(1l+TP(2)+TP(3)+TP(4))/4. s l)i'-i l = 0 • 0 SUi·i2=0.0 SU/·13=0 .0 SUiV;-=0 .0 D 0 L, I = l ' f1! U=(TP(I)-XMl*FKP(I) 1/=(TP(I l-Xrlj)::o:c2 s lJi'·i l = s u i·'i 1 + u

. 4 S l J H 2 = S lJ ,',i 2 + V R 1 = S lJ f -·, 1/ S U H 2 D 0 5 I= 1, 1'1 P=(TP(Il-XMl*BKP(l) n = ( T P ( I l-X H ) :;c* 2 SUH3=SLJV,3+P

5 Slm4=SUH4+Q R2=SUM3/SUM4 .

---1') :~ HI I '• 0 0 ' ( i p ( I ) ' F k p ( I ) ' B I< p ( I ) ' I = 1 ' N ) PRH.JT 102 PRINT l03,R1 P R I N T l 0 4 , _R 2 PRINT 102 DO 10 I=l,N \ D F F ( I l - -:~ ::: T ( I l ::q L 0 G F ( ( F K ( I ) * P K ) / ( G K * T ( I ) ) ) ) DFI~( I l=-R;:cT( I );:q LOGF'< (BK( I l*PK)/(CK*T( I)))) J) H F ( I ) = -R :;, ( R 1 + T ( I ) l u 1-! b ( 1 l - -R :;, ( R 2 + I ( I ) ) D SF ( I ) = ( D 1-1 F ( I ) - DF F ( I ) ) IT ( I )

10 D S B ( I l = ( 0 H B ( I ) - DF B ( I ) ) IT ( I )

B~A= -R2*R PRINT 105 P R 1 ~~ 1 1 o o , ( T (I ) , oF F ( 1 ), D F B U I , DH F ( I ) t DR B ( I ) , I =l t N ) PRINT 102

l 4

PR I iH 106 ·pi< P!T 10 1 , ( T ( I ) , DS F ( I ) t DS B ( I ) t I= 1 t N) P P. u: T 10 2 PRI~T 200,FEA,BEA

·r := (Jf'YA l ( I 2 ) ---::-;-:-t- Ci-(~i:·, i.\ T ( 3 E 1 B • 3 )

~ r) 0 F G R i-i AT ( 5 F 1'~ • 4 ) ~.n 1 10 :~ JG3 l ()I;.

1- li f< i .. ·,,\ T ( I ) FORi·iA ·I-(5X,;u~HSLOPE OF 1/T VS Lf\J(K-F)=,Fl4.4) rORHAT ( 5X, 2L~HSLOPE OF 1/T VS LN ( K-R) =, Fl4.4)

74

.LOS F 0 R i "~~ -~· ( 9 X , HIT , 9 X , 9 H DE L T A F-F , 5 X , 9 H DE L T A F-R , 6 X , 9 H DEL T A 1 L T I\ H-R)

H-F,6X 7 9HDE

lOG l 0 () 200 300

FOr-z::,J.\·1· (9X,lHT,9X,9HDELTA S-F,5X,9HDELTA S-R) FO Ri-i/11 (13X 7 3H1/T 7 13X 7 6HLN K-F,11X,6HLN K-R) FORMAT (5X,5HEA-F=,F14.4,5X,5HEA-R=~F14.4). F 0 R f·l AT ( L, E 18 • 8 ) F 0 RH A 1 ( 3 F 18 • it ) CALL EXIT Ei\!D

1 /T .0033 • 00 31 .0030 .0027

:· 1

LN K-F 1.81:18 1. R4.46 1. 8739 1.9469.

· ,;

. ' i' .

LN K-R 6.4168 6.3623 6.2383 6-.1003

SLOPE OF 1/T VS LN(K-Fl= SLOPE OF 1/T VS LN(K-~)=

-238.3776 587. 5() 71

" T 303.00()() 313.0000 333.0000 363.0000

I

303.0000 3.13.0000 ;333.0000 363.0000

EA-F=

DELTA F-F 16653.9180 17203.3600 18324.2220 19984.6490

DELTA S-F I

-55.3872 -55.4365 -55.5923 -55.7362

•

. 473.6563

DELTA F-R 13881.4230 14393.6010

· 15'~36. 4440 16988.8740

DELTA S-R -51.6530 -51.7028--51.8483 -52.0042

DELTA H-F -128.4046 -148.2746 -188.0146 -24 7. 6246

. E·A-R= -1167.3767

-1769.1;-377 -1789.3077 -1829.0477 !

-1888.6577

APPENDIX B

LIST OF GOMPliTER PROGRAMS~RROR CALOJLATIONS)

A Program for Computing the Effect of Error in Temperature on

Activation Energies

~~FE CT nF ERRnR IN TEMPERATUR~ ON ACTIVATION ENE~GIES : J I i i E i' ! S I Oi'·l T ( 2 5 ) , F I<( 2 5 ) , B K ( 2 5 )

__ __:[ ~ = l. CJ(3 7 p :-: = 6 • 6 2 5 ~:: ( 1 0 • );t ~:c ( - 3 4 • ) ) C ;< = l • ::., 8 0 ::: ( 10 • ,;c);: ( -2 3 • ) ) fH=O. l Dll =-0. l DrJ 1 1=1,3 READ lOO,(T(I),FK(I),BK(I),I=l,4) Rr:I:.D 100, FE A, B Ef~ Dn 2 J=l,4 Tl=T(Jl -( ;,.> = T ( J)

Uf1 3 L=l,l1 u= 1 = ( ( F E t-\ l ~::( T 1 >:: :;: 2 ) ) I ( T ( J ) ,;: ::: 2 ) EF2=((FEAl*(T2**2lli(T(Jl**2l Eb l=( (t.l:Al~~(Tl::::;cz) li(T(J):;c:::2) ~~?=(( HE Al*(T2**2lli(T(J)**2) D i: f 1 = - ; ~ ::: I l :;: L 0 G F ( ( F 1\( J ) >:: P 10 I ( C K ~:c T 1 ) ) DFF2=-R*T2*LOGF((FK(Jl*PK)/(CK*T2l)

. DFBl=-R* Tl*LOGF((BK(Jl*PK)/(CK*Tl)) DF ~2=-R*I2*LOGF((BK(J)*PK)/(CK*T2)) DH F1=-R*((-EF1/R)+T1) DHF 2=-R::: ( ( -EF2/R) +T2) i! H H l = -R :;: ( ( - E 81 I R ) + T 1)

o;-;:, z=-R::: ( ( -EB2/R) +T2) DSI: 1= ( DI-IF l-UFF 1) /T1

.------.-J~ F2- ( DHF2-Df-F2) /TZ DS8 l=( DHB1-DFB1l/T1 D S U2 = ( DH B2-DF 82) IT2 Pf~IiH 200, 11,EF1,Eo1,DSF1,DSI:H i>R INT 200, T2, EF2, EB2, DSF2, DSB2 Tl=Tl+DT

-~~~2= I 2+ c OiH I i'JU E C Oi'lT I i'llJ E c i . , .j t:

l 0 0 F DR r•i A l ( 4 E 18 • 8 ) \

75

8 FORMAT(5X,5HTEMP.,6X,4HEA-F,6X,4HEA-Rt3X,9HDELTA S-F,3X,9HDELTA S---~l"""'lfl

200 FO~MAT(5F10.2) CALL EXIT

76

Ti:; I P. E A-F---·-8 A-1{ DELTA S-F iJ 1.: L { A-S:---R--3 0 3 • 0 0 '~ 7 3. 6 'j -116 7 • 3 7 - !:i ~. 3 8 - !:i 1 • 6 5 303.00 473.65 -1167.37 -55.38 -51.65 303.10 473.97 -116~.15 -s5.3B -51.65 302.90 473.34 -1166.60 -!55.38 -51.65 303.?0 474.28 -1168.92 -55.38 -51.65

--3 0 2-~-ci_,.o--,~ 7 3 ;tY3-::Tr6s-.-tf3·---_..;::.5..;:..,.:>-=-. -;;-3~8---~5.:;:...1 -=-. 76,:;-t ----

303.30 474.59 -1169.69 -55.38 -51.65 302.70 472.72 -1165.06 -5!5.38 -51.64 303.40 474.91 -1170.46 -55.38 -51.66 302.60 472.41 -1164.29 -55.38 -51.64 303.50 475.22 -1171.23 -5!5.38 -51~66

---302~5~0---4~72.09 -1163~.~5~3~----~5~5-=-.=3=8------=571-=-.~6~4-------

303.60 475.53 -1172.00 -55.38 ... -51.66 302.40 471.78 -1162.76 -55.38 -51.64 3 o 3 • 7 o 't; 5 • e 5 -117 2 • 1 n -' ~ • ~fA -!51 • 6 6 302.30 471.47 -1161.99 -55~30 -51.63 303.80 476.16 -1173.55 -55.38 -51.66

--302.?.0 471.16 -1161.22 -55.38 -51".63 303.90 476.47 -1174.32 -55.38 -51.67 302.10 470.85 -1160.45 -55.38 -51.63 304.00 476.79 -1175.09 -55.38 -51.67 302.00 470.53 -1159.68 -55.38 -~1.63

313.00 473.65 -1167.37 -55.43 -51.70 313.00 473.65 -1167.37 -55.43 -51.70 313.10 473.96 -1168.12 -55.43 -51.70 312.90 473.35 -1166.63 -55.43 -51.70 313.20 474.26 -1160.87 -55.43 -51.70 312.no 473.05 -1165.88 -55.43 -51.69 313.30 474.56 -1169.61 -55.43 -51.70 312.10 472.75 -1!65.14 -55.43 -51.69 313.40 474.87 -1170.36 -55.4~ ~51.11

312.60 472~45 -1164.39 -55.43 -51.69 313.50 475.17 -1171.11 -55.43 -51.71 312.50 472-14 -1163.65 -55.43 -51.69 313.60 475.47 -1171.85 -55.43 -51.71

-3 12 • ,, 0 4 7 1 • 8 l~ - 11 6 2 • 9 0 - 5 5 • 4 3 - 5 1 • 6 9 313.70 475.78 -1172.60 -55.43 -51.71 312.30 471.54 -1162.16 -55.43 -51.69 313.80 476.08 -1173.35 -55.43 -51.71 312.?0 471 •. 24 -1161.42 -55.43 -51.68 313.90 476.38 -1174.10 -55.43 -51.71 312.10 470.93 -(160.67 -55.b3 -51.68 314.00 476.69 -1174.85 -55.43 -51.72

. 31z.OO 470.63 -1159.93 -55.43 -51.68 333.00 4/3.65 -ll6fe37 -55.59 -51.84 333.00 473.65 -1167.37 -55.59 -51.84

77

TE_U~- E_~_E- EA-R DELTA S-F DELTA S-R 333.10 473.94 -116u.OB -55.59 -51.84 3:.2.90 1.~73.37 -1166.67 -55.59 -51. R'~ 3:;3.?0 '~ 7'~. 2?. -116J.71J -55.59 -5l.f\5 332.rl0 473.09 -1165.9-, -s~.59 -5l.H't 333.30 '~74.51 -1169 ·'~8 -~!J.59 -5l.BS 33~.70 472.80 -1165.27 -5~.59 -51 • H'~

---··-·~---·--· ,; 7'4 .-"(i:J-~Tf7 if.- i o -5-5.59 3::13. '~0 -51.05 332.60 472.52 -1164.57 -55.59 -51.84 333.50 475.08 -1170.88 -55.59 -51.85 332.50 472.23 -1163.87 -55.59 -51.84 333.60 475.36 -1171.59 -55.59 -51.85 332 ·':-0 '~71.95 -1163.17 -55.59 -5_1. 83 333.70 475.65 -1172.29 -55.59 -51.85 332.30 471.67 -1162.'t7 -55.59 -51.83 333.RO 475.93 -1172.99 -55.59 -51.86 ;,\;J2.?.0 471,38 -1161,77 -5~.59 -51·83 333.90 4,76. 22 -1173._69 -55.59 -51.86 332.10 471.10 -1161.07 -55.59 -51.83 33'r.OO 476.50 -117 4. '~0 -55.59 -51.86 332.00 470.81 -1160.37 -55.59 -51.83 363.00 473.65 -1167.37 -55.73 -52.00 363.00 473.65 -1167.37 -55. 73 -52.00 363.10 473.92 -1168.02 -55.73 -52.00 362.90 473.39 .-1166.73 -55. 73 -52.00 363.20 474t~18 -116i3.66 -55.73 -52.00 362.80 473.13 -1166.09 -55.73 -52 .oo 363.30 4 7'-1-. 4'~ -1169.31 ~55.73 -52.00

'362.70 '~72.87 -1165.45 -55. 73 -51.99 363.40 4 7Lr. 70 -1169.95 -55.73 -52.00 362.60 472.61 -1164.80 -55. 73

(.

-51.99 363.50 47tr.96 -1170.59 -55.73 -52 .o 1 362.50 472.35 -1164.16 -55.73 -51.99 363.60 '~- 75. 22 -1171.24 -55.73 -52.01 362 ·'~0 472.09 -1163.52 -55. 73 -51.99 363.70 4 75 •'rR · -1171.88 -55.73 -52.01 362.30 "~71.R3 -1162.88 -55.73 -51.99 3iiT:'80 475.7 5 -1172.53 -55. 73 -52.01 362.20 471.57 -1162.24 -55.73 -51.99 363.90 "~-76.01 -1173.17 -55.73 -52.01 362. 10 471.31 -1161.59 -5.::>. 73 -51.99 364.00 476.27 -1173.82 -55.73 -52.01 362.00 471.05 -1160.95 -55.73 -51.98

78

A Program for Correcting Equilibrium Rate Constants

':'LIST PRINTER C C***22439CN461W SHETH, R P 03/02/66 FORTRAN 2 0030 002 0

~C ___ CORR EC TED ___ EQUI LI BRI UM__CONSTANTS __ ANILACTLVAJ_H1N __ E_N_ERG_LE.5 DIMENSION DFF(lO),DFB(lO),OHF(lO),OHB(lO),OSF(l0),0SB(l0),BK1(10) DIMENSION T(10),FK(lO),BK(lO),FKP(lO),BKP(lO),TP(lO),EQK(l0)

_DIMENSION EQ(lO) ------~------~--~-----------------------READ 7 9 1'1

READ 8,R,PK,CK ___ READ __ 300 ,_(_T_ll_L,_f_K_il_lt_B.K..L.( I.._,_) tz.-1.....::==-..lLl,uN.LJ)L-_______________ _

AKM=l.6E-18 AKA=2.0E-20

_EK=(.65)/(.35*.35) ___ _ DO 9 I=l,N

9 EQK (I)= (FK( I )*AKM) I( BK( I )*AKA) G=_EK_IE_QI\_L4:J. ___________________________ _

DO 41 I=l,N 41 EQ(I )=EQK(I>*G

_DO 311=1,N ______________________ _ 31 BKl(I)=(FK(I)*(AKM/AKA))/EQ(I)

PRINT 202 ____ PRINJ_lQ __ c-2 ______________________________ _

PRINT 20 1 ,( T ( I ) , EQ (I ) ,I= 1, N) DO 1 I= 1, N-

------ _BKP (I )=LOGF( BKlUJJ FKP( I )=LOGF (FK( I))

1 TP(I)=1./T(I) __ _,XM = _(_lP_ (1 ) + T P ( 2 ) + T P ( 3 ) + T P ( 4) ) /4,

SUM1=0.0 SUM2=0.0 SUM3=0.0

...--------- SU M4 =0. 0 - ------

DO 4 I=1,N ____ U_=_( TP __ (_I_)__::~_)~_K.~P!-!-( I~t->----------------------

V=(TP(I)-XM)**2 SUM1=SUMl+U

_______ 4:_ SUfv12=.SU M2 +V Rl=SUM1/SUM2 DO 5 I=l,N

___ P= ( TP_( I_)_~.X.MJ~-IL~-'------------------------0-;,-(TP (I) -XM) **2 SUM3=SUM3+P

___________ 5_ SU~14=SU.M4+Q ----------------,---------------------R2=SUM3/SUM4 DO 10 I=l,N

___ oFF ( Ij =-R*T_LU~Jj._O_G_F_U FK (,-!I~>...:.*-!..P~Kw.).!-/..l.(~C!.!.K*..:...T.!..l:-( ~I .t-) >.t->w>~----------DFB-fi >=-R*T( I)*( LOGF( ( BKl( I )*PK) ICCK*TI.I)))) DHF( I )=-R*(Rl+T( I))

79

D H B ( I ) = -R * ( R 2 + T ( I ) ) .. _____ __ D SF U )_:: ( D ljf_UJ_-:_DF:_F_UJJ LLliJ·---------...,-------------

1 0 D S B ( I ) = ( D H a ( I ) -OF a ( I ) ) IT ( I ) FEA=-Rl*R

_ . BE A= -R 2 * R ______________ __ ______ _ - -- --------PRINT 102 PRINT 105

____ p R INT_lOO ,_(~tLl,DFE (I) ,.DEB (I), DHE (I), DHB (I) t I= 1 ,N) PRINT 102 PRINT 106

________ ___ PRINT _ 10 1, ( J( IJ , DSE_(_I__)_, _0$_8_1lJ __ , _l=-l.t...Nu.l_. _ .. ------------ ____ _ PRINT 102 PRINT 200,FEA,BEA

_ _ _ _7_EOR MALLI2J ----------------------------8 FORMAT(3E18.8)

100 FORMAT(5Fl4.4) lOLFORr~AT_ (3Fl4.4) ______ _________ _ 102 FORMAT(/) 105 FORMAT(9X,lHT,9X,9HDELTA F-F,SX,9HDE~TA F-R,6X,9HDELTA H-F,6X,9H~f

- - -_ --~L TA .H:-.RJ __ 106 FORMAT (9X,lHT,9X,9HDELTA S-F,5X,9HDELTA S-R) 200 FORMAT (5X,5HEA-F=,Fl4.4,SX,SHEA-R=,Fl4.4)

__ __ 202 __ _ FORMAT(6X,31HCPR_REC_T_EO ____ EQU_I __ Ll.BRLU_M_C_O_~_SJ"AN.T_S_} ______ _ __ _ _ _ 201 FORMAT(6X,2HT=,Fl0.2,6X,l4HK-EQUILIBRIUM=,Fl0e2) 300 FORMAT (4El8.8) ·.

------~-~-~~r~--------------------------------------------------------END

80

CORRECTED EQUILIBRIUM CONSTANTS

--- --- ---------T= 303.00 K-EQUILIBRIUM= 3.37 T= 313.00 K-EQUILIBRIUM= 3.68

_T= __ ___ 333.00 ___ _ _____ K-EQUILIBRIUM= _____ ___ 4._29 T= 363.00 K-EQUILIBRIUM• 5.30

--------------------------------T DELTA F-F DELTA F-R DElTA H-F DELTA H-R

303.0000 16653.9180 14748.5370 -128.4046 -1769.4377 _________ 313 .oooo __ 17203.3600 ___ 152B9.413o. ___ -_ 1A8 .• 2746. __ ~~ 789. 3077_

333.0000 18324.2220 16389.4120 -188.0146 -1829.0477 363.0000 19984.6490 18027.6950 -247.6246 -1888.6577

T DELTA S-F DELTA S-R _303.0000 _____ ~55.387_2 ____ -:5_4.5_14_7, ____________ _ 313.0000 -55.4365 -54.5646 333.0000 -55.5923 -54.7100

__ _..3..6..3.. • ..0.0.0.0 -5.5 -13 62 -54. 8 65 9

_____ E A::F = ____ 4, 1_~_._6_2_!;,_3._· ---'EA-R.==-,--_-__,.1_ .!!o-16!!...L7~· 3o!...7..w6>!...7.._ ___________ _ •

81

APPENDIX C

LIST OF EQUIP~1ENT AND MATERIALS

EQUIPMENT

Gas Onomatogranh. F & H, Hodel 720. Range: 0-200 milliamperes

d-e. Manufactured by: F & M Scienti fie Corporation,

Avondale,, Pennsylvania.

Hypodermic Syringes.

1. Size: 10 microliters. Model 701-N. Manufactured by:

llamilton Company, Incorporated, Whitter, California.

2. Size: 2 cubic centimeters. Hanufactured by: Eisele

and Company, Nashville, Tennessee.

Thermostat. ~1odel S-6, Voltage: 750. Manufactured by:

Instruments for Research and Industry, Cheltenham,

Pennsylvania.

~1ATERIALS

~!ethyl Crotonate: It was prepared in the laboratory. B.P. *: 128°

Centigrade _at pressure of 748 mm. llg.

Diethyl ~'lalonate: Lot No. 7636; !'vlatheson, Coleman and Bell Company.

It was redistilled at 98° centigrade and 41 millimeters of

rae rcury pressure.

Phenyl Cy<:lohexane: Grade: Practical; Lot No. 391075, Matheson,

Coleman and Be 11 Company, Non·.rood, Ohio.

-------------------------------·---*Lange's Handbook of Chemistry, 1949.

Tertiary Butyl Alcohol (2-methyl-2-propanol): Lot No. 17,

Matheson Chemical Company; M.P.: 24.5-25.5° Centigrade.

Potassium t-Butoxide Solution: it was prepared by dissolving

freshly cut potassium metal in ~-butyl alcohol.

Potassium Carbonate, Anhydrous: Granular, Lot No. 23088,

J. T. Baker 01emical Company, Phillipsburg, New Jersey.

82

BI BLIOGIW'IIY

1. ABRAHOVITCJI, R. and STRUBLE, D., Tetrahedron Letters, No. 39, 289 (1966).

2. ALEXAl~DER, E., Principles of Ionic Organic Reactions, p. 151, John \~iley and Sons, Inc., New York, New York (1950).

3. A'IBROSE, D., Gas Chromatography, Van Nostrand, Princeton, New Jersey (1962).

4. DERGHAl~N, E., GINSBURG, D. and PAPPO, R., Org. Reactions, 10, 179 (1959).

83

5. CONAl\JT, J. and WI!ELAND, G., J. Am. Chern. Soc., 54, 1212 (1932).

6. CONDON, F. and HEISLICil, II., Introduction to Organic Chemistry, p. 546, Holt, Richard and Winston, Inc., New York, New York (1960).

7. CO NNOR, R. and ~1C CLELLAN, W., J. Org. Chern.,~~ 570 (1939).

8. DESTY, D., Gas Chromatogrflphy, Acedemic Press, New York, New York (1958).

9. FA~\1ER, E. and ROSS, J,, J, Chern. Soc., 2358 (1925).

10. IBID, 1570 (1926).

11. FROST, A, and PEARSON, R., Kinetics and Mechanism, pp. 123-262, John Wiley and Sons, Inc., New York, New York (1961).

12. GARDNER, J. and RYOON, H., J. Chern. Soc., 42,45,48 (1938).

13. GLASTONE, s., Textbook of Physical Chemistry, p. 1044, ~lac~li 11 an and Co. , Ltd. , London (1956).

14. GOULD, E., 1·1echanism and Structure in Organic Chemistry, liolt, Richard and Winston, Inc., New York, New York (1959).

15. III NE, J., WIESLOECK, R. and GHIRARDELLI, R., J. Am. Chern. Soc., 83, 1219 (1961).

16. HOLDEN, N. and LAP\'IORTH, A., J. Chern. Soc., 2368 (1931).

17. !lOUSE, II., ~1odem Synthetic Reactions, p. 164, w. A. Benjamin, Inc., New York, New York (1965).

18. INGOLD, C., Structure and ~fechanism in Organic Chemistry, pp. 692-695, Cornell University Press, Ithaca, New York, New York (1953).

84

19. JA\IES, w. and HARTIN, D., Biochern. J. , so ~-"679 (1952).

20. JONES, \v. ' J. Am. Chem. Soc., 105 __ , 1547 (1914).

21. KJ\.\ iLET I M. and GLOVER, D., J. Am. Chern. Soc., 7.]., 4896 (1955).

22. KAPLA.~ I L. and GLOVER, D., J. Am. Chern. Soc., ~. 84 {1965).

23. KEULHlA.~, A., Gas Ouornatography, Reinholti Publishing Corp., New York, New York (1957).

24. KOELSOi, C., J. Am. 01em. Soc.,~, 437 (1943).

25. KORST, J., Haster of Arts Thesis, Dartmouth College, llanover, New llarnpshirc (1958).

26. LAIDLER, K., 01emical Kinetics, McGraw-Hill Co., New York, Ne\'1 York (1950).

27. LITTLEWOOD, A., Gas Ouomatography, Academic Press, New York, New York (1958).

28. ~1C COY, L., J. Am. Chern. Soc., 80, 6568 (1958).

29. ~fC ELVAIN, S. and COHEN, H., J. Am. Chern. Soc., 64,260 (1942).

30. i·IC ELVAIN, S., Olern. Rev., 45, 479 (1941).

31. MEHTA, K., Maste.r of Science Thesis, University of Missouri at Rolla, Rolla, Hissouri (1965).

32. NOGAI<E, S., Gas-Liquid Chromatography, Inter. Science, Ne\Y' York, Ne\Y' York (1962).

33. OGATA, T., OKAi'W, M., FARUYA, Y. and TABUSIII, I., J. Am. 01ern. Soc., .z!, 5426 (1956).

34. PEARSON, R. and DILLON, R., J. Am. 01em. Soc., 7S ~j 2439 (1953).

35. PECSO K, R., Principles and . Practice of Gas Chromatography, John Wiley and Sons, Inc., Nev,r York, New York (1959).

36. PETER, s., 1-lcchanisms in Organic Chemistry, p. 143, John \~iley a.nd Sons, Inc., Ne\v York, New York (1963).

37. PIIILLIPS, C., Gas Chromatography, Academic Press, Neh' York, New York (1956).

38. PURDIE, T. , J. Chern. Soc., 4 78 (1891).

39. PUR.l\JELL, II., Gas Chromatography, John Wiley and Sons, In~. Nel'l York 1 New York (1959).

40. I~OBElUS, J. and CASERIO, ~!. 1 _Basic Principles of Organic C1emistry, w. A. Benjamin, Inc., New York, New York (1964).

41. SNIUEL, D. and GINSBURG, D., J. Chern. Soc., 1288 (1955).

42. S~!Af<EI~, P. R., Ph.D. Thesis, University of Wisconsin, ~-ladison, Wisconsin (1951).

43. SHAFER, P. R., LOEB and JOIL'JSON, J. Am. Chern. Soc., 75, 5963 (1953).

85

44. SlliHt.:-1URA, O. and INA!'-10TO, N., Bull. Chern. Soc. Jap., ~~ 529 (1955). ·.

45. STEIN, L. and ~1URPIIY, G., J. Am. Chern. Soc., 2!1 1041 (1952).

46. SUGDER, S. and \'liLLS, J.,J. Chern. Soc., 1360 (1951).

'47. SWAI~, G., J. Chern. Soc., 1039 (1955).

48. TSURATA, T., YASHUARA, Y. and FARUKAWA, J., J~ Org. Chern., ~. 1246 (195 3).

49. l'/ASSER\1ANN, A., ~lonatsch, ~~ 543 (1952).

50. \'tEISSBERGER, A., Technique of Organic Chemistry, Rates and ~lcchanism::; of Reactions (Part I), pp. 499-578, Inter. Science, New York, New York (1961).

51. WIBERG, K., Physical Organic Chemistry, pp. 374-393, John l'li1ey and Sons, Inc., New York, New York (1964).

52. \'JULF~1AN, D., ~laster of Arts Thesis, Dartmouth College, Hanover, New Hampshire (195 8).

53. \'lULFHAN, D., ~1EIITA, K., SHETH~ R. and SIIAFER, P., Abstracts of Papers Presented at the 15lst ~leeting, ACS, Division of Organic Chemistry of the American Chemical Society, Pittsburgh, Pennsylvania, Harch 28-31, 1966.

54. ZELLERS, G.'and LEVINE, R., J. Org. Chern., _!l, 911 (1948).

ACKNOWLEDGEMENTS

The author is privileged to express his idebtedness to

Dr. D. S. Wul fman for his guidance and encouragement \Y'i thout

whose aid and backing, portions of the present research would

not have been realized.

86

Appreciation is extended to Dr. s. B. Hanna, Dr .• R. M. l'le llek

and Dr. P. R. Shafer (Dartmouth College, New Hampshire) for their

valuable suggestions during the investigation.

Acknowledgement is made to the Chemistry Department for

the use of the gas chromatographic equipment and for the financial

aid during the period of September, 1965 to January, 1966.

Acknowledgement is also made to~Mr. Charles F. Segar, III

for preparation and purification of a number of reagents·.

VITA

The author was born on June 22, 1941. He · received his

elementary and high school education in Bombay, India.

After graduating from Jai Hind College (University of

Bombay) in ~·lay, 1962 with a B. Sc. degree in Chemistry, he came

to the United States in September, 1962. He received a B.S •

• degree in Chemical Engineering from the Hissouri School of

Mines and Hetallurgy (the name was changed to University of

~1issouri at Rolla in July, 1964) in May, 1964.

In September, 1964 he enrolled in the graduate school.

During the period of September, 1965 to January, 1966 he \'las.

employed as a Student Assistant by the Chemistry Department of

the University of Missouri at Rolla.

87

kinetics and mechanisms of base-catalysed reactions

Documents