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Masters Theses Student Theses and Dissertations
1966
Kinetics and mechanisms of base-catalysed reactions
Rohit Panalal Sheth
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This thesis is brought to you by Scholars' Mine, a service of the Missouri S&T Library and Learning Resources. This work is protected by U. S. Copyright Law. Unauthorized use including reproduction for redistribution requires the permission of the copyright holder. For more information, please contact [email protected]. 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
~... . ii 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 iii 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 • 87 VITA • • • • • •• • • • • • • • • • • • • • • • • • • • • • iv
LIST OF FIGURES
Figure Page
1. Standard Curve of Area-Ratio as a Function of ~1ole-Ratio • • • • • • • • • • • 36 2. Concentration of Adduct as a Function of Time (Run 1) • • • • • • • • • • 43 3. Concentration of Adduct as a Ftmction of Time (Run 2) •• • • • • • • • • 44 4. Concentration of Adduct as a Function of Time (Run 3) •• • • • • • • • • 45 S. Concentration of Adduct as a Function of Time (Rtm 4) • • • • • • • • • • 46
6. Concentration of Adduct as a Function of Time (Run 5) •• • • • • • • • • 47 v
LIST OF TABLES Table Page I Reported Equilibrium Yield of Adduct at Various Temperatures • • • • •• • • • • • 9
II Experirental Data for Run 1 • • • • • • • • • 38 III Experiroontal Data for Run 2 • • • • • • • • • 39
IV Experimental Data for Run 3 • • • • • • • • • 40
v Experimental Data for Run 4 • • • • • • • • • 41
VI Experimental Data for Run 5 • • • • • • • • • 42 VII 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 vi
GLOSSARY OF TERMS
Ea Arrhenius activation energy
6F* Free energy of activation
6H* Heat of activation h Plank's constant Boltzman constant Rate constant
Ke Equilibrium constant Ka Dissociation constant for adduct
Kb Dissociation constant for base (~·Buok)
Km Dissociation constant for malonic ester
R Gas constant
6S* Entropy of activation
T Absolute reaction temperatu~
SUBSCRIPTS f Forward process r Reverse process 1
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: 2
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. 3
~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. 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. 4
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). 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). 5
CHART 1
MICHAEL REACTIONS
COOC2H5 CH3 CH3 COOC2H5 I I I I CH CH Ql CH I 2 t --... -BuOK (2) II I COOC2IIs + CH 012 I I .. t - BuoA I OJOC2H5 I COOCH 3 000013
diethyl II malonate III roothy1 croton ate 1,1 - dicarbethoxY -3 - carbomethoxy -2- · 111ethy1 propane
COOC2H5 I r3 IH3 (3) II ----- CH doubtful CH ----- 01COOC2H5 I route I COOC 2H5 CH
coo~" rooc2H5 . IV ,) v
(4) v CH I 3 COOCH3 CH I II + 012 C013 I COOC2H5 boc2H5 VI VII 6
CHART 2
VARIENTS OF THE MICHAEL REACTION (6)
-COOR
-COR
-CONH2
-N02 -C- CH- L I 1 -so2R Basic Catalyst L2 - Oi - L3
RCOO- -illOR -CH2- RCD- -roR
NC- -Oi
B2NCO- -illNH2 o2N- -N02
RSO - -so R 2 2 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+ ~ .. Cll --- Lz 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 8
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 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 at
Diethyl Malonate + Ethyl Crotonate 65
+ Ethyl Cinnamate 35
+ Ethyl p,f-dimethyl 30 70 -acrylate
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. 10
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).
CHART 4
GENERALLY ACCEPTED ~1ECHANIS~f OF NORi\fAL MICHAEL REACTION
- + (5) 0-12 (COOC2H5 ) 2+B:...... !"' :CH(COOC2H5) 2+B:H ,s ,_ VIII , ,- (6) .,..c = c - c • 0 + :CH(OOOC2 H5 ) 2 ~ [ c .. c = c -:.=..-o] VIII ~(C02C2H5)2 II I IX (7) IX B~H - c - Qi - c = 0 ~ I Cll(C02C2H5) 2 III 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 II (9) XI + H R - c - Cll2 - CH2 .- CN XII 12
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 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) • 13
QlART 6
~AMLET AND GLOVER ~IECHANISM
K-Buffer (10) H Buffer + A Buffer- + HA
NH - c = 0 Nil - C = 0 I I K Barb. I I_ (11) 0 = c 012 +A 0 = C 01 + HA I I I I NH - c • 0 NH -. C = 0 XIII
Nll - c • 0 --!... I I - (12) XII I + Ph - 01 = Oi - N02 _ 0 = c IH - Ol(Ph)-OI-N02 b I NH - c = 0 XIV Nil - c = 0 a I (13) XIV + HA 0 = ! II - QI(Ph) -CH2-N02+A b I NH - c = 0 XV
Nil - c = 0 a I I_ +HA (14) XV + A 0 = c C - CH(Ph)-CH2-No2 .. 6 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 16
(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 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 Clli 3 ~0 2 Et CH + llC C - Na II I I Cll HI - CH3 002Et I co2Et 002Et
OIART 9
Holden and Lapworth ~1echanisrn
CH 3 I C0 2Et Cll3 002Et Cll I .· I I (19) II + CHR HC CR CH I I I I C02Et QI C02Et 12 C02Et 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 c Et (21) HC t ro 2 dccomposi tion I H HC co2Et ~III I ro 2Et IXX 18
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.
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 + CIIC0 2C2H5 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 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; 23 CHART 11 Addition of Ni troform to Methy1acry1ate C(N0 2) 3 CH2Cll 2co 2cH 3 MeTNB l-IIN02 NF ~leA -C(N02)iQI = CHC02 c11 3 DNU DNS · · 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 + DNU + No- Olr___..... 2 , where An- = C(N02) 3CH2CHCOzCH3 ; cq- = CII2CHOHC02CJI3 C(N0 2) 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 25 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 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 26 !_-butyl alcohol was obtained prior to the publication of the above work (53). 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 30 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) 6li* = -R d(lnK*) = -R[d(lnk) + T] d (1/T) d(l/T) The entropy of activation, 6S*. = +611* - 6F* = (35) 6S* R(T d(lnk) + 1] T dT ln~- 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 32 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 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 33 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: 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 • • • • • • • • • • 3so "c Injection port temperature • • • • • • • 300 °C Oven temperature • • • • • • • • • • • • 170 °C Current. • • • • . ' ' . • • • • • • • • 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 ~~~ ~~~ 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 39 TABLE II I Experimental Data for Run 2 Reaction Temperature = 40° ~ ,2°C Sample Time, Area of Adduct Adduct-Cone. No. Hours Area of Standard Moles/liter· 1 5 0.14 70 0,1038 2 10 0.2140 0,1511 3 15 0,2640 0,1865 4 20 0.3060 0.2161 5 25 0,3280 0,2317 6 30 0.3390 0,2394 7 35 0.3540 o. 2500 8 40 0.3640 0.2571 9 50 0.3800 0. 2684 10 60 o. 3850 0,2719 11 70 0.3860 0,2726 12 80 0.3915 0.2 765 13 90 0.3990 o. 2818 14 100 0.4040 0.2853 15 110 0.4100 0.2896 40 TABLE IV Exnerimental Data for Run 3 Reaction Temperature = 60° ~ .2°C Sample Tire, Area of Adduct Adduct-Cone. No. Hours Area of Standard Moles/liter 1 5 0.1780 0.1257 2 10 0.2400 0.1695 3 15 0.2900 0.2048 4 20 0.3330 0.2352 5 25 0.3550 o. 2507 6 27 0.3344 0.2362 7 30 o. 3675 0.2596 8 35 0.3800 o. 2684 9 42 o. 3925 0. 2 772 10 so 0.4100 0.2896 11 60 0.4140 0.2924 12 71 0.4225 0.2984 13 80 o. 4275 0.3019 14 90 o. 4285 0.3026 15 100 0.4325 0.3055 16 110 0.4370 0.3087 41 TABLE V Experimental Data for Run 4 Reaction Temperature = 70° _:: .2°C Sample Time, Area of Adduct Adduct-Cone. No. Hours Area of Standard Moles/liter 1 5 0.2080 0.1469 2 10 o. 2530 0.1787 3 15 0.3030 0.2140 4 20 o. 3450 0.2437 5 25 o. 3680 0.2599 6 30 0.3820 0.2698 7 34 0.3930 0.2776 8 40 0.4070 o. 2875 9 50 o. 4250 0.3002 10 60 0.4290 0.3030 11 70 0.4330 0.3058 12 80 0.4380 0.3094 13 89 o. 4440 o. 3136 14 100 0.4470 o. 315 7 15 110 0.4510 o. 3185 42 TABLE VI Experimental Data for Run 5 Reaction Temperature = 90° .:!:. .2°C Sar.1ple Time, Area of Adduct Adduct-Cone. No. Hours Area of Standard Moles/liter 1 5 0.2100 0.1483 2 7 0.2419 0.1709 3 10 0.2800 0.1978 4 18 o. 3499 o. 24 71 5 20 0.3700 0.2613 6 25 0.3950 0.2790 7 30 0.4100 0.2896 8 35 0.4200 0.2966 9 40 o. 4350 o. 3072 10 45 0.4467 0.3155 11 50 o. 4550 0.3214 12 60 0.4600 o. 3249 13 70 0.4650 0.3284 14 80 0.4700 0.3320 15 90 0.4720 0.3334 16 100 o. 4 750 0.3355 17 109 0.4790 0.3383 o.-3o 0.25 0.20 ...,.. u ::l "0 Run 1. Reaction Temperature = 30°+0.2°C ~ tH 0 .::: 0.15 0 •P'I..., CIS ...,$-4 c:: 8 u6 0.10 o.os 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 Figure 3. Concentration of Adduct as a Function of Time. o:3s· ---.---, -l r -- , • ,-.---, ·-.-· 0.30 0.25 Run 3. Reaction Temperature = 60°+0.2°C 0.20 0.15 (' 20 40 60 80 100 120 Time, Hours Figure 4. Concentration of Adduct as a Function of Time. o;3s 0.30 ._; u :l ""::) o. 25 :i Run 4. Reaction Temperature = 70°+0.2°C 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. o. 30 h ...,a> ·~...... Ill .....a> 0 :2 0.25 ...,.. 0 :l Rtm s. Reaction Temperature = 90°+0.2°C "< ~ 0 c:.:: 0.20 0 ·~ ~ C'CI ...,... s:: a> 0 c:.:: 0 u 0.15 o.lo 20 40 60 80 100 120 Time • Hours Figure 6. Concentration of Adduct as a Function of Time. 48 Chapter V DISCUSSION A. Discussion of Data and Results: In investigating the kinetics of the addition of diethyl 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, 49 TABLE VII De?cndence of Rate Constants on Temperature* Ter.1pcrature** . kf 0 C Liter · r·1ole s lr,lin. -1 K*** ~ e = v·r • 30 6.122 612.1 0.80 40 6. 326 579.6 0.87 60 6.514 512.0 1.02 70 6.304 460.1 1.10 90 7.007 446.3 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. 50 TABLE VIII Equilibrium Yields at Various Reaction Temperatures Temperature* % Yield of the Product . a·c at Equilibrium ** 30 58,3 40 59,6 60 62,0 70 63.1 90 64.9 *Measured up to ~ 0.2°C. **Based on the reported value of the equilibrium yield of 51 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. 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 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* cal T t:.P t:.H* ~ t:.s* e. u. Temperature, mole mole if ' oK t:.F f t:.F t:.II" t:.S « t:.S" *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 + c2H5I -(C2H5 ) 4N+I- -38 to-47 B. c2H5N + CH3I-C2H5N+OI3+I- -29 to -35 + - + -34 to -61 C6II5COCII2Br =" Br- o. c2H5N + CH3I __.,. (C2H5 ) 3N+cH3+ r- -34 to -41 3. Reaction between Ions (33) 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 = CliC0 20I3 __..., -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 OR (37) c - R3 + II II c ~ l\2 Rl XXVI Cli302C o- I I n.3 - c c - OC2115 I I ... n.2 - c - C- X I ~1 H XXVII I XXVIII a XXVIIIa or XXVIII or XXVI XXVI lib (38) XXVII I a co 2CII3 ..illL. I 3 XXVII Ib 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 ~o 2 ;.1e 0 ~o 2 Me 0 - I I IIc::::-=--c c- OEt uc::=-c C-OEt cis I I I I IIIIJIIIIC ~-== COzEt H 111111C C -=::::::1 H ~ · - ~ I CII 3 II CII3 cq2Et ~o 2 ~1e o- ~o 2 Me 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). CHART 15 Interpretation of McCoy's Work mtc o- \/ c ll + /c\ co 2 r.-~ R Cll R Cl 3 y co 2r-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 l{;II5CIICH2COR .. . ~ .. CII2- C(OC 2II5 ) 2 • 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. Significance 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 ) 13 (17) 17.79(34 ) 13.30 (5) 2 2 5 2 R-CII (COOCll 3) 2 15 19.70 14.70 1 R -CII(COOCII3) 2 26 25.69 (CH3) 3COH 19 19.00 CH3CII = CIICOOCH2CH3 14 R = CH31IICII2 COOCH2 CIJ3 Rl = CH 31HCII(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. 61 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 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 nearly 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. 62 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. ' 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 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. 65 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. 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 illzEt I I_ CH c I I 013 ro 2Et which is not the classically accepted species co2Me I -CH cn2Et I I Cll CH I I CH3 C02Et 67 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. 68 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 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. 71 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 ------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= AKl=Al/(AKM*C) AK2= A2/ ( AKA*C) AKBL=(AKl*AKM)/(AK2*AKA) PRINT 104,AKl,AK2,AKBL PRINT 101 ----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 K-8ACKWARD R-EOOILIBRIOH 6.1224 612.0693 .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 ,' 1E i·l S I 0 i'l T ( 10 ) , r= K ( 10 ) t B K ( 10 ) , F KP ( 1 0 ) , B KP ( 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 ) , BK ( I ) , I =1 , N ) PI~ Ii'!T lOR DO 1 I= 1, •"I 3 I< P ( I ) =L 0 G F ( BK ( 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 JH 2 =S lJ ,',i 2 + V R 1 = S lJ f -·, 1/ S UH 2 D0 5 I= 1, 1'1 P=(TP(Il-XMl*BKP(l) n = ( T P ( I l-XH ) :;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 ) ' BI< 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 L0 GF ( ( 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) HF ( I ) = -R :;, ( R 1 + T ( I ) l u 1-! b ( 1 l - -R :;, ( R2 + I ( I ) ) DSF ( I ) = ( D1-1 F ( I ) - DF F ( I ) ) IT ( I ) 10 DS B ( I l =( 0 HB ( I ) - DF B ( I ) ) IT ( I ) B~A= -R2*R PRINT 105 l 4 PR 1 ~~ 1 1o o , (T (I ) , oF F ( 1 ), DF BU I , DH F ( I ) t DR B( I ) , I =l t N) PRINT 102 74 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 :~ 1- li f< i.. ·,,\ T ( I ) JG3 FORi·iA · I-(5X,;u~HSLOPE OF 1/T VS Lf\J(K-F)=,Fl4.4) l ()I;. rORHAT ( 5X, 2L~HSLOPE OF 1/T VS LN ( K-R) =, Fl4.4) .LOS F 0 Ri "~~ -~ · ( 9 X , HIT , 9 X , 9 HDE LT A F-F , 5 X, 9 HDE L T A F-R , 6 X, 9 HDEL T A H-F,6X 7 9HDE 1 LT I\ H-R) lOG FOr-z::,J.\·1· (9X,lHT,9X,9HDELTA S-F,5X,9HDELTA S-R) l 0 () FO Ri-i/11 (13X 7 3H1/T 7 13X 7 6HLN K-F,11X,6HLN K-R) 200 FORMAT (5X,5HEA-F=,F14.4,5X,5HEA-R=~F14.4). 300 F 0 Rf·l AT ( L, E 18 • 8 ) F 0 RH A 1 ( 3 F 18 • it ) CALL EXIT :· 1 Ei\!D 1 /T LN K-F LN K-R .0033 1.81:18 6.4168 • 00 31 1. R4.46 6.3623 .0030 1. 8739 6.2383 .0027 1.9469. 6-.1003 · ,; . 'i' . SLOPE OF 1/T VS LN(K-Fl= -238.3776 SLOPE OF 1/T VS LN(K-~)= 587. 5() 71 " T DELTA F-F DELTA F-R DELTA H-F 303.00()() 16653.9180 13881.4230 -128.4046 -1769.1;-377 313.0000 17203.3600 14393.6010 -148.2746 -1789.3077 333.0000 18324.2220 · 15'~36. 4440 -188.0146 -1829.0477 ! 363.0000 19984.6490 16988.8740 -24 7. 6246 -1888.6577 I DELTA S-F I DELTA S-R 303.0000 -55.3872 -51.6530 3.13.0000 -55.4365 -51.7028- ;333.0000 -55.5923 -51.8483 363.0000 -55.7362 -52.0042 • EA-F= . 473.6563 . E·A-R= -1167.3767 APPENDIX B 75 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 Ei '! 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) Di: f 1= - ;~ ::: I l :;: L0 GF ( ( F 1\( J ) >:: P10 I ( CK ~:c T1 ) ) 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 DS 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 Al ( 4 E 18 • 8 ) \ 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 -=-. 7 6,:;-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'~ ---··-·~---·--· 3::13. '~0 ,;7'4 .-"(i:J-~Tf7 if.-i o -5-5.59 -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 DH B ( I ) =-R * (R 2 + T ( I ) ) ..______DSF U )_:: ( Dljf _UJ_-:_DF:_F_UJJ LLliJ·------...,------1 0 DS B ( I ) =( DH 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 FORMA T(9X,lHT,9X,9HDELTA F-F,SX,9HDE~TA F-R,6X,9HDELTA H-F,6X,9H~f - - -_ -- ~L TA .H:-.RJ __ 10 6 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) ·. ------~END-~ -~~r~------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 _____ EA::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. 82 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. 83 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). 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 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). 85 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 43. SHAFER, P. R., LOEB and JOIL'JSON, J. Am. Chern. Soc., 75, 5963 (1953). 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). 86 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. 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·. 87 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.