KINETICS OF BASIC HYDROLYSIS OF A HOMOLOGOUS

SERIES OF SUBSTITUTED LACTONES

DISSERTATION

Presented in Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the Graduate School of The Ohio State University

%

THOMAS JOHN DOUGHERTY, B. 8.

The Ohio State University

1959

Approved by

Adviser Department of Chemistry ACENOMLEDGMËNT

I would like to express my sincerest appreciation to Dr. Harold

Shechter for suggestion of this problem, for his gudidance during the course of this investigation, and in particular for many interesting and inspiring discussions throughout the course of writing this dissertation.

I should also like to thank my colleagues for the loan of their time and equipment.

I am grateful to the Standard Oil Company of Ohio and to the

National Science Foundation for fellowship funds.

11 Dedicated to the memory of my Mother whose intellectual curiosity I hope someday to attain.

iii TABLE OF CONTENTS

Page

I. INTRODUCTION 1

II. THEORY AND HISTORY

Mechanism of saponification of Lactones. . . . Factors Affecting Saponification Rates of Lactones and Esters...... 5 Bimolecular Water Hydrolysis of beta-Lactones. lU Reactions of beta -Isovalerolactone in Water . 15 Effect of Solvent on Rates of Saponification of Lactones...... 16 Previous Investigations...... 17

H I . DISCUSSION AND INTERPRETATION OF RESULTS 23

Scope of Present Investigation ...... 23 Saponification of Homologous Unsubstituted Lactones ...... 27 Effect of Methyl Substitution on Reactivities of Lactones...... 36 Substituted L-membered lactones ..... 37 Substituted 5-membered lactones ...... h2 Substituted 6 -membered lactones ..... kB Substituted 7-membered lactones ...... 51 Relative Effects of Substitution on the Saponifi­ cation of Lactones of Various Ring Size . . . 52 Entropy Effects on Saponification of Lactones . . 59 Summary of Results ...... 62

IV. EXPERIMENTAL 6It

Preparation and Purification of Materials. . . 6U 1,2-Diraethoxyethane...... 6k 3-Ifydropropanoic Acid Lactone ...... 6k 3-Hydroxy-2-methylpropanoic Acid Lactone 65 3-%droxybutanoic Acid Lactone. .... 66 3-Hydr03qr-2,2-dimethylpropanoic Acid Lactone ...... 68 3-Hydroxy-3-methylbutanoic Acid Lactone 67 4-Hydroxybutanoic Acid Lactone. .... 69 li-Ifydroxy-2-methylbutanoic Acid Lactone 69 li-Hydroxypentanoic Acid Lactone .... 70 li-Hydroxy-2,2-dimethylbutanoic Acid Lactone 71

IV TABLE OF CONTENTS (CONTD.)

Page

IV. EXPERIMENTAL (Gontd.)

Preparation and Purification of Materials (Gontd.) l|.-Hydroxy-3i3-dimethylbutanoic Acid Lactone. . . . 71 i;-Hydroxy-li-raethylpentanoic Acid Lactone.... 70 . 5-Hydroxypentanoic Acid Lactone...... 73 5“Hydroxy-2-niethylpentanoic Acid Lactone ..... 7k 3“Hydroxyhexanoic Acid Lactone ...... 76 5-Hydro3{y-2,2-diinethylpentanoic Acid Lactone . . . 77 $-%rdro%y-3,3-dimethylpentano ic Acid Lactone . . . 76 5-Hydroxy-5“-inethylhexanoic Acid Lactone..... 78 6-Hydroxyhexanoic Acid Lactone...... 79 6-Hydroxyheptanoic Acid Lactone...... 79

Determination of Kinetic Constants...... 80 Equipment...... 80 Constant Temperature Baths ...... 80 Conductometric Equipment ...... 80 Conductivity C e l l s ...... 81 Hypodermic Syringes...... 81 Kinetic Techniques...... 81 Solvents and Standard Solutions...... 81 Preparation and Execution of a Kinetic Run .... 82 Calculations...... 61;

APPENDIX...... 93 IIST OF FIGURES

Figure Page

1-7 Representative Plots of t (Rcq-R) versus R for Basic Hydrolysis of Lactones......

7-26 Activation Energy ( a H^) Plots for Basic hydrolysis of Lactones...... 101

VI LIST OF TABLES

Table Page

I. Saponification Bates and Dipole Moments of Homologous Lactones...... 8

II. Kinetics of Alkaline Hydrolysis of Homologous Lactones in 1,2-Diraethozyethane-water (63.i|:36.6^ by wt.) by Sodium Hydroxide...... 9

III. Effect of Ring Substituents on the Ifydrolysis of Homologous Lactones...... 18

IV. Kinetic Data for Saponification of Lactones by Ifydroxide Ion in l:2-Dimethoxyethane-water (ItLby vol. at 2^®) 2h

V. Effect of Solvent Composition on Rates of Saponification of Homologous TJnsubstituted Lactones...... 28

VI. Equilibrium Data for Reaction of Ketones with Hydrogen Cyanide...... 2t8

vn. Absolute and Relative Rates of Saponification of Homo­ logous Substituted Lactones...... 53

VUI. Rates of Hydrolysis of beta-Isovalerolactone as a Function of Concentration ; '...... 91

IX-XCIX Kinetic Data for Saponification of Lactones by Sodium Hydroxide...... 120

Vll I. INTR0DUCTK3Ï

The objectives of the present study are: (1) to determine effects of ring size and substituents on the basic hydrolysis of lactones; (2 ) to determine and interpret the kinetic parameters of basic hydrolysis of lactones; (3) to obtain information concerning electrical and steric effects on hydrolysis of various lactones;

(ii) to obtain information vith respect to the conformations of lactones and their reaction intermediates; (5) to obtain more information concerning the lack of reactivity of the beta-propio- lactone system; (6 ) to obtain general information concerning kinetic effects in heterocyclic molecules in congparison to their correspond­

ing carbon coiqpounds and; (7) to extend in general the knowledge and theories of cyclic molecules.

For these purposes, a homologous series of mono-methyl and gem- dimstiyl substituted lactones containing U, 5, 6 and 7 ring atoms were synthesized and their saponification rates determined at three

temperatures in 1 ,2-dimethoxyethane-water (1:1 by volume, 25°).

Enthalpies and entropies of activation were calculated from the rate constants at three tenperatures. The parent, unsubstituted lactones of this series were studied for comparison with the sub­

stituted lactones and for comparison with previous data obtained in a solvent of different composition. II. THEORY iWD HISTORY

Mechanism of Saponification of Lactones

Base-catalyzed hydrolysis of lactones has been a subject of considerable study. The previous investigations ■which are pertinent to -fche present study will be summarized briefly.

In common with open-chained esters, the usual mechanism of saponification of lactones involves acyl-oxygen fission with formation of the -hydroxyalkanoate ion (1). The o-verall reaction and -fche apparent mechanism of hydrolysis are indicated as follows:

0 (CÎ2)yj - G — OH fast

fast u -0-J slow

fast , ^ O 0 - (CHg)^ - GOgH — _Y HO - (CHg)^ - COg . (1)

(1) See C. K. Ingold, Structure and Mechanism in Organic Chem- istry, Cornell l&iiversity Press, I-thaca, N.Ÿ., i?^3, chapter lit, p. 7^2 -781, for a discussion of ester l^drolysis.

The hydrolysis exhibits second order kinetics, first order with respect to lactone and first order with respect to hydroxide ion.

Saponification experiments conducted in water enriched wi-th 0^^ support acyl-oxygen fission in lactones. Bothy^ -butyrolactone (2 )

2 3 and fi -butyrolactone (3) yield the corresponding hydroxybutanoate ions in which 0^® is introduced only in the carboxylate groupj

Equations 2 and 3*

(GHg)] - C = 0

+ O H ^ — > HO - (GHg)^ - GOg^ ^ ; (2)

ÏÏ2 C=o g)l8 , - I + OH --- » HQ - GH (GH3) - GHg - GOg (3) GH3 - CH

(2) F. long and L. Friedman, J. Am. Ghem. Soc., 72, 3692 (1950).

(3) A. Olson and J. Hyde, J. Am. Ghem. Soc., 2^59 (19W-)*

Stereochemical evidence further supports acyl-oxygen fission.

Thus, hydrolysis of optically active -butyrolactone by hydroxide ion yields fi -hydroxybutanoic acid with 95-98% retention, (it) In neutral

(it) A. Olson and R. Miller, J. Am. Ghem. Soc., 60 , 268? (1938). or slightly acidic solution conplete inversion (98-99%) is noted, indicating alkyl-oxygen fission, whereas in solutions of pH -2 to

+2 mixtures of isomers are obtained. Acyl-ozygen fission of simple T A esters by hydroxide is also siçported by 0 (5) and stereochemical

(6 ) evidence.

(5) M. Poljsmyi and A. Szabo, Trans. Faraday Soc., 508 (193k),

(6 ) B. Hoimberg, Her., 2997 (1912). The existence of a reaction intermediate rather than a single transition state in attack of certain esters by hydroxide ion has been adequately demonstrated by Bender (?)•

(7) (a) M. Bender, J. A. Chem. Soc., 73, 1626 (1951); (b) ibid., 80 lOkb (1958). ““

In hydrolysis of alkyl (ethyl, ^-propyl and t-butyl) benzoates con­ taining 0^® in the carbonyl group it was found that the 0^® content was decreased in the esters recovered after partial saponification.

This demonstrates that an intermediate, symmetrical species must exist sufficiently long to participate in a reversible step, i.e..

18 18 pl8 HoO, - OH QH T R - CO-rrR^ + O H ^ R - OR1 :-----► R - Ç - OR^ DH ^---- 6h

18 fi 1 18 A Ç.H R - C - OR + OH R - J - OR <£>

RCOg - H + OR

It will be assumed in subsequent discussion that saponification of lactones involves a similar intermediate, and further that this 5 intermediate approximates the structure and the energy of the transi­ tion state for the rate-determining step (8).

(8) In theory it is possible that (deconçosition of inter­ mediate) is rate-determining. This however does not seriously alter the inteipretation since the transition state for decoagposition of intermediate will likely be very close in energy and structure to that for formation of the intermediate.

Recently it has been found that the slow step in saponification of ethyl benzoate and of benzamide is formation of the intermediate as has been previously assumed (7b). By measuring concurrently, the rate of 0^® exchange and the rate of hydrolysis of ethyl benzoate. Bender was able to determine the rate constant for formation of the addition intermediates (k^ in schematic on p.V ) and has shown it to be very nearly equal (slightly less) to the rate constants for overall hydroly­ sis. Measurements at different temperatures allowed calculation of activation energies for the various steps. It was found that step 1

(formation of intermediate) accounts for essentially all of the over­ all activation energy for hydrolysis.

Factors Affecting Saponification Rates of Lactones and Esters

In all cases studied, alkyl substitution proximal to the carbonyl groïç) or alkyl oxygen results in decreased rates of saponification of esters (9). The results have been interpreted in terms of electron

(9) For exanple see, (a) C. K. Ingold, Structure and Mechanism in Organic Chemistry, p. 758, and (b) M. S. Newman, Steric Effects in Organic ckemistiy, John Wiley & Sons, Inc., 1956, pi ^20. 6 donating properties of alkyl groups and in terms of steric hindrance.

The marked steric effect associated with hydrolysis of esters con­ taining atoms in the 6-position to the carbonyl oxygen atom was pointed out by Newman (9b). In general, lactones appear to follow the same general trends as do open-chain esters (10).

(10) For exançle, see Table III, p. 18.

It has long been known that I4.-, 5-, 6 - and 7-membered lactones hydrolyze more rapidly than do corresponding open-chained analogs and larger ring lactones. Two recent interprétations of this effect have been postulated.

The first of these, that of H. K. Hall, Jr. (11), considers direction of approach of hydroxide ion. If it is assumed that the

(11) H. K. Hall, Jr., J. Am. Chem. Soc., % , 6U20 (1958). hydroxide ion attacks approximately in the plane of the carbonyl group

(transition state A), as has been postulated in N-carboanhydrides (12),

A cis-lactone B trans-ester

(12) D. Ballard and G. Bamford, J. Chem. Soc., 355 (1958) 7 unfavorable electrostatic repulsion between the lone pair atom dipole of oxygen and hydroxide ion is avoided because of the cis configurations required by the ring. In open-chain esters, this repulsion cannot be avoided because of the preferred trans configuration(transition state B). Consequently esters are hydrolyzed at slower rates than are comparable lactones.

A different interpretation has been developed by Huisgen (13).

(13) (a) R. Huisgen, Angew. Chem., 3lA (1957)j (b) R. Huisgen and H. Ott, Tetrahedron, 6 , 253 (1959).

He proposes that the Icwer-membered lactones (U-7 members) are held in the cis form (A) and possess relatively large dipole moments as conqpared to a trans form (B). The cis-form contains more energy than

Î I O

(A) (B) open-chained (trans) and higher-membered (trans) lactones. There are therefore smaller energy differences between initial states and rate- controlling transition states for cis lactones than for trans lactones

(lit), resulting in more rapid saponification rates. Huisgen*s results are tabulated below. 8

(lU) The relative difference in dipoles of cis and trans-lactones is removed in the transition state if it is assumed that the resonance of the alkoxyl-oxygen and the carbonyl group is a principle contributor to the dipole (this overlap is destroyed in the intermediate).

Table I

Saponification Rates and Dipole Moments of Homologous lactones* (R. Huisgen and H. Ott, Ref. 13 b.)

No. Atoms in k2 (1 ^6 . X min.), 0° Ring of Lactone (Debye) 60:40 Dioxane-water

1^** 3.8** 5 4.09 7.88 6 4.22 3.30 7 4.45 15.3 8 3.70 21.2 9 2.25 0.696 10 2.01 0.0013 11 1.88 0.0033 12 1.86 0.0198 13 1.86 0.0360 1.86 0.0180 16 1.86 0.0390 n-Butyl 1.79 0.054Ù Caproate

* Base = sodium hydroxide, temp. 0° ** T. Gresham, J., Jansen and F. Shaver, J. Am. Chem. Soc., 70, 998 (1948).

The effects of ring size on the rates of saponification of unsub­ stituted U- through 8-msmbered lactones have been studied by Matuszak

(15) • It was found that the 6-raembered lactone hydrolyzes much more

(15) C. A, Matuszak, Ph. D. Dissertation, The Ohio State Univer­ sity (1957). Table II

Kinetics of Alkaline Hydrolysis of Homologous lactones in 1,2-Dimethoxyethane-Water {63»h/36,6% by wt.) by Sodium Hydroxide (15)

0 k2 ASÎ lactone Ten#)., (l./m. X min.) (kcal./mole) (e.u.)

3-Hydroxy- propanoic -20.93 1.68 12.8 -lk.65 Acid -5.36 7.66 lactone -0.03 12.71 l;-Hydroxy- -20.93 1.11 butanoic -0.03 7.56 12 .k -17.18 Acid 25.03 51.1 lactone

5-Hydroxy- -20.93 lOU pentanoic -5.36 302 8.7 —22.68 Acid -0.03 ii28 lactone

6-Hydroxy- -20.93 1.97 hexanoic -0.03 10.5k 10.7 -22.87 Acid 25.03 59.9 lactone

7-Hydroxy- -20.93 3.66 heptanoic -0.03 17.2 9.k -26.62 Acid 25.03 78.3 lactone

(15) G. A. Matuszakf Ph. D. DissertationI, The Ohio State University (1957). 10 rapidly than do the other lactonesj the relatively rapid, rate was reflected primarily as an enthalpy effect (the entropy factor is actually less favorable than for the U- or ^-membered lactones).

The fact that ^-valerolactone is hydrolyzed more rapidly than

y -butyrolactone is in general agreement with current theories

concerning relative reactivities of trigonally substituted 5- and

6-membered ring compounds containing carbon or homorphic heteroatoms.

In a trigonally substituted 6-membered ring of chain conformation, the hydrogen atoms on adjacent carbon atoms which are normally conplete- ly staggered, are brought into partial eclipsing by virtue of the twisting of the methylene groips in adjusting to the trigonal center

(16). Since the rate-determining step in the saponification involves

(l6) H. Brown, J. Brewster, and H. Shechter, J. Am. Chem. Soc., 76, hS7 (1951i). changes of trigonal (sp^) carbon atom to a tetrahedral (sp^) carbon atom, the hydrogen atoms move from partially eclipsed positions to those of conplete staggering with subsequent release of strain from non-bonded interactions. (The overall driving force is much greater than the steric resistance resulting from introduction of 1,3-interac­ tions.) This accounts in part for the relatively rapid rate observed

in saponification of the 6-membered lactone.

The ^membered lactone undergoes basic hydrolysis at a slower rate than does the 6-membered homolog. This fact is also primarily accountable in terms of strain factors involving non-bonded inter- 11 actions. In this trigonally substituted lactone there are 6 non­ bonded interactions from 3 pairs of eclipsed hydrogen atoms and the electron pairs dm alkoxyl oxygen. In the reaction interniediate for saponification two additional pairs of interactions arise when the trigonal carbon is converted to a tetrahedral center. The formation of the intermediate will therefore be relatively unfavored in the

3-membered lactone; this situation is in contrast to that of the 6 - membered lactone in which formation of the reaction intermediate results in a decrease in non-bonded interactions (17). It should be

(17) Since the 3-membered carbocyclic ring is believed to be somewhat puckered (K.S. Pitzer, Science, 101, 672, 19U5) the hydrogen atoms are not completely eclipsed. This however does not alter the argument with the S-membered ring since conversion of a trigonal to a tetrahedral center will still result in increased strain from increased non-bonded interactions. noted that effects due to differences in dipole moments (see p . 7 ) are not being considered. The differences are small and probably not significant in determining relative reactivities of h- through 7- membered lactones.

The 7- and 8-membered lactones hydrolyze at rates comparable to that of the 3-membered lactone, both being slightly faster. Interpre­ tation of these results is very similar to that for the 3-meiribered lactone, in that conversion of the trigonal centers to tetrahedral in the reaction intermediates causes an increase in strain resulting from non-bonded interactions and compression of van der Waal radii. 12

The saponification of the it-membered lactone proceeds at a rate interiaediate between that of the 5~ and 6 -membered lactones, it's enthalpy is greater (unfavorable) than either, but its entropy is more favorable (greater) than either. Reasons for the relatively high activation energy for this lactone are not obvious in light of current theories of small ring conqpounds. The strain in the l^-membered ring is thought to be primarily caused by bond angle distortion. The sum total of bond angle distortion, bond opposition forces and com­ pression of van der Waal radii is defined as I-strain (18). If bond angle distortion is dominant, it is anticipated that a trigonal center

(18) H. C. Brown, J. Chem. Soc., 12lt8 (1956).

(as in a lactone) in a U-membered ring will have a relatively great tendency to become tetrahedral. Althou^i the absolute magnitude of this angle change (10.5°) is equal in all rings, regardless of size, the relative effect on the difference in energies of the ground state and transition state should certainly be greater the smaller the trigonally-substituted ring (i.e. 3>U> 5?6). Interpretation of the high activation energy has therefore been made in terms of possible stabilization of the ground state of fi -propiolactone by resonance forms such as: 13 (S> 0 0 0 0

{ = i ■ =

' ' X / \ ! ' X CH2 CH2 CH2 CH2

Solvent effects may further contribute to the relative stability of the it-membered lactone. If the ground state of the i^-merabered lactone is more highly solvated than that of the other lactones and/or the intermediate is solvated to a lesser extent than its homologs, a higher enthalpy of activation and a more favorable entropy of activa­ tion would be expected (other factors being equal). Some evidence which may indicate this to be the case may be found in the anomalous acid hydrolysis of ^ -lactones. It has been shown (19) that under acid conditions, -propiolactone and /A -butyrolactone hydrolyze at a rate proportional to Hammett's Hq function (20); whereas y*-butyrolactone

(as do esters) undergoes acid hydrolysis at a rate proportional, not to Hq but to (21). This indicates that water is not required

(19) F. Long and M. Purchase, J. Am. Chem. Soc., ^ 326? (1950).

(20) L. P. Hammett, Physical Organic Chemistry, McGraw-Hill Book Co., Inc., New York, 19U0, p. 273.

(21) F. Long, F. Dunkle, W. McDevit, J. Phys. Chem., 55, 829 (1951). “ in the rate determining step for acidic hydrolysis of /5 -lactones, but is necessary in the rate controlling step for acidic hydrolysis of t* -lactones. One interpretation of this result may be that the U- li; merabered lactones are sufficiently solvated so as to require no additional water in the rate determining step.

Bimolecular Water Ifydrolysis of beta-Lactones

Four-membered ) lactones also undergo bimolecular reaction with water or alcohol in neutral or slightly acidic solution with alkyl-o:qrgen fission (22). Thus, beta-propiolactone reacts with

(22) For a summary of the evidence for the mechanism see C. K. Ingold, Structure and Mechanism in Organic Chemistry, p. 765-767. neutral methyl alcohol to form 3-methoxypropanoic acid whereas with methoxide ion the product is methyl 3-hydro%ypropanoate (23);

OHj 0

.0=0 + OH,OH CHjO-OHg- OHj-O-OH

U (C) + OCH^ -^.SO-CHg-CHg-C-O-GHj .

y -Butyrolactone on the other hand does not react with neutral water or alcohol, but undergoes alkyl-oxygen fission with cyanide (2h), mercaptide or alkoxide ion(25) by attack at the position alpha to the ring oxygen atom;

0 H2 C CHg I I + X ® >X CH9-CH9-CH9-C-O ^ . 0 OH2

C II 0 X ® - cn” , r s “, r o “ 15

(23) P. Bartlett and P. Rylander, J. Am. Chem, Soc., 73, ^273 (1951)«

(2b) W. Wislicenus, Ann., 233, 101 (1686); G. Blanc, Bull. soc. chim. France, C33 , ^ , 8 7 9 (1905) •

(25) E. Fittig and K, Strom, Ann., 267, 186 (I892); H. Plieninger, Ber., % , 265 (1950); L. Scholte, Arkiv. Kemi, 8, b57 (1950).

Reactions of 3-Hydro3ar~3~methylbutanoic Acid Lactone in Water.

The reactions of 3-hydroxy-3-methylbutanoic acid lactone (beta- isovalerolactone) in aqueous solution have been recently investigated

(26 ). It was found that along with neutral, acidic or basic hydrolysis

(26 ) H. Liang and P. Bartlett, J. Am. Chem. Soc., 3585 (1958), respectively, the lactone undergoes a simultaneous decarboxylation reaction. Methods were devised for measuring individually the rates of these reactions. beta-Isovalerolactone undergoes basic hydrolysis at a slower rate than does 3-hydroxybutanoic acid lactone (beta- butynolactone) or 3-hydroxypropanoic acid lactone (bete-propiolactone), neutral hydrolysis of beta-»is0valerolactone occurs about a hundred times faster than does bata-butyrolactone at 25°; acid hydrolygis follows the Hammett Hq functions and occurs approximately a thousand times faster than does beta-butyrolactone.

If the neutral and acid hydrolyses of this lactone proceeded by the same mechanism as for beta-propiolactone or beta-butyrolactone

(bimolecular alkyl-oxygen fission and unimolecular acyl-oxygen fission 16 respectively) this tertiary lactone would be expected to react at a slower rate than primary or secondary lactones (acid-catalyzed and neutral hydrolysis of beta-propiolactone occurs more rapidly than that of beta-butyrolactone). On this basis it is concluded that unimolecular alkyl-oxygen fission occurs with beta-isovalerolactone in both acid and neutral hydrolysis. By similar reasoning, since the rates of basic hydrolysis decrease in going from the primary to the secondary to the tertiary lactone, beta-isovalerolactone under­ goes saponification by normal bimolecular acyl-oxygen fission.

The decarboxylation is presumed to involve the same intermediate

(tertiary carbonium ion resulting from alkyl-oxygen fission) as is formed in acid or neutral hydrolysis^

HxO. H.C C = C H ^ + C O , H jC/

H,C.

H.C OH

Effect of Solvent on Saponification Rates of Lactones.

The effects of solvent composition on the basic hydroly­ sis of ii-hydroaypentanoic acid lactone ( êT -valerolactone) have been determined (27). In methanol-water the hydrolysis rate 17

(27) E. Toramila and M. Ilomaki, Acta Chem. Scand,, ^ 12li9 (1952).

decreases as the concentration of water is decreased; there is a

concomitant increase in activation energy and a decrease in entropy

of activation. The same general trend is ; noted for ethanol-water

mixtures containing greater than O.Oij. mole fraction of ethanol.

With smaller amounts of ethanol there is very little change in

the rate constant.

Previous Investigations

The data from previous studies of lactones pertinent to this

investigation are summarized in Table III. In general 6-membered

lactones with the exception of the geminal 3-substituted derivatives

hydrolyze at much faster rates than do k-, 5- or 7-membered lactones.

It is also seen that alkyl substitution in all cases decreases the

rates of hydrolysis. However, since in some cases different solvent

systems, different kinetic techniques, and different temperatures were

enployed there is a lack of consistency in the data. In addition there

is insufficient data in most cases to permit determination of en­

thalpies and entropies of activation. Interpretations based on

these data are therefore questionable. 18

Table H I

The Effect of Ring Substituents on the Hydrolysis of Homologous Lactones

Tenp. k2 Solvent Kinetic Parameters References (l./mol. X min.)

3-Hydroxypropanoic Acid Lactone

0.07 16.6 H2O Ea, 13.k kcal./mole (11) 6.90 29.1 log A, 10.16 25 130 25 72 H2 O(28) 25 119 HgO (29)

3-Hydr oxybutano ic Acid Lactone

25 50 H2O (29) 35 90 HpO Ea, 13.3 kcal./mole (30) 30 72.5 log A, 13.5 25 51.2 20 35.0 25 72 HgO (28) 25 h9.2 HgO (31)

3-Hydroxy-2-methylpropanoic Acid Lactone

25 litO HgO (29)

3-Hydroxy-3-methylbutanoic Acid Lactone

25 13.2 HgO (26) 19

Table III (Contd.)

kg Tenç». Solvent Kinetic Parameters References (l./mol. X min.)

Ji-Hydroxybutanoic Acid Lactone

25 51.6 HgO (31) 25 70 H2 O (26) 0 13.8 15 3h.9 HgO Ea, 11.3 kcal./mole (31;) 0 11.8 log PZ, 8.3i| 25 55.8 (lU) 25^ (35) ethanol 30 60.7 k3% Ea, 120 kcal./mole (36) acetone 20 30.0 log A, 10.1: 10 lit.9 25 50 H2 O (37) 25 ii8.6 H2 O (11) 0 8.88 60 % (13) dioxane

ii-5ydroxypentanoic Acid Lactone

25 25.9 (IL) H2 O (32) w 39.2 H2O Ea, 11.15 kcal./mole (27) 25 2L.3 log A, 7.775; 15 12.5 = -25 an. 0 lt.28 30 23.6 h3% Ea, 12.3 kcal./mole (35) acetone 20 11.7 log log A, 18.2 10 5.57 25 28.0 H2 O Ea, 11.2 kcal./mole (3U) 15 lii.l; log PZ, 7.89 0 l|.9it 25 25.0 H2O (37) 25 18.6 HgO (11)

U-Hydroxy-2-methylbutanoic Acid Lactone

25 3L.3 «20 (37) 20

Table H I - ( cpntd. )

TeiiÇ). ^2 Solvent Kinetic Parameters References (1,/mol. X min.)

ii-Hÿ'droxj-ii-methylpentanoic Acid Lactone

25 9.06 H2 O (37) 30 7.17 h3% Ea^ 11.1; kcal./mole (37) 20 3.79 acetone log A, 9.07 10 1.89

5-Hydroxypentanoic Acid Lactone

25 30.1; (12;) 25% (37) ethanol 25 11.00 H2 O (37) 25 6.22 H2O (11) 0 3.30 60% (13) dioxane

^Hydroxy-2-methylpentanoic Acid Lactone

25 6.85 H2O (37)

5-Hydroxyhexanoic Acid Lactone

25 6.1;0 H2 O (37)

5-Rydroxy-5-methylhexanoic Acid Lactone

25 5.51 HgO (37)

5-Hydroxy-5-methylheptanoic Acid Lactone

25 3.27 H2 O (37) 21

Table III (Contd,)

■ Temp. Solvent Kinetic Parameters References (l./mol. X min. )

5-Hydroxy-3,5-dimethylhexanoic A d d Lactone

25 5.05 HgO (37)

5-Hydroxy-li,5-dimethylhexanoic Acid Lactone

25 It.lO HgO (37)

6-Hydroxyhexanoic Acid Lactone

25 h6.2 HpO (11) 0 15.3 60 % (13) dioxane

6-Hydroxy-3,7-dimethyloctanoic Acid Lactone

25 O . W i HgO (37) 22

References for Table III

(19) F. Long and M. Purchase, J. Am. Chem. Soc., 72, 326? (19^0).

(28) P. Bartlett and G. Small, J. Am. Chem. Soc., 72, 1^867 (1950).

(29) H. Johansson, Chem. Zentr., Vol. 1X87> 557 (1916).

(30) A. Olson and P. Youle, J. Am. Chem. Soc., 73, 2^68 (1951)«

(31) A. Olson and R. Miller, J. Am. Chem. Soc., 2687 (1938).

(26) H. Liang and P. Bartlett, J. Am. Chen. Soc., 3585 (1958).

(32) P. Henry, Z. Physik, Chem. ID, 98 (1892).

(33) E. Caldin and J. Wolfenden, J. Chem. Soc., 1239 (1936).

(3U) D. Hegen and J. Wolfenden, J. Chem. Soc., 508 (1939).

(35) S. S. Guha Sircar, J. Chem. Soc., 898 (1928).

(36) C. Stevens and P. Tarbell, J. Org. Chem., 19, 1996 (195ii).

(37) H. Sebelius, Diss. Lund, 1927; Information reported in W. Huckel, Theoretlsche Grundlagen Per Organischen Chemie, Akademische Verlagsgeseilsckaft in.b.H., Leipsiz, 1953, Vol. II, 2nd, ed., p. 259-262 .

(38) Calculated from data in reference 7.

(11) H. Hall Jr., J. Am. Chem. Soc., 80, 61^20, (1958).

(13) R. Huiâgen, Angew. Chem., 3kl (1957).

(27) E. Tommila and M. Iloraaki, Acta Chem. Scand., 6, 12U9 (1952). n i. D3SCÎJSSI0N M D INTERPRETATION OF RESULTS

Scope of Present Investigation

The kinetics of reaction of homologous U-, 6- and 7-membered lactones and certain of their mono and gem-dimethyl derivatives with hydroxide ion have been studied in 1,2-dimethoxyethane-water (1:1 by volume at 25°). Saponification velocities were measured conducto- metrically (See Experimental) at three temperatures in the one solvent system in order to determine the thermodynamic enthalpies ( , entropies (^ S^) and free energies (4E^) of activation. Second-order rate constants and kinetic parameters from the present study are summarized in Table 17. The kinetic data obtained in each experiment are contained in the Appendix, Tables DC toXClX • Representative straight-line plots for determination of rate constants (t (Rqq-R) vs. R), and activation energy ( plots for all the compounds in­ vestigated are also included in the Appendix, Figures 1 to 7 and

Figures 7 to 26 respectively.

In general 6-raembered lactones hydrolyze much more rapidly than do the corresponding 1+-, 5- or 7-membered derivatives. The i:-, 5- and 7-membered homologs hydrolyze at similar rates, the order in general being k'>7>5* This generalization will hold to approxi­ mately 350°. With the exception of the 6-merabered lactones, which usually have relatively low enthalpies of activation, the kinetic;

23 Table IV

Kinetic Data for Saponification of Lactones by Hydroxide in 1,2-Dimethoxybthane-water (l:l by volume at 25f)

No. of Ring kgCl./m. X min.) ^H^(±0.3) nst±l) Lactone Atoms -0.05° 14.0 16.1 25.0° (kcal./mole) (e.u.) (kcal./mole)

1 . 3-Hydroxypropanoi c Acid Lactone 4 20.1+0.1 67.2+0.9 119+0 11.0 - 20.6 17.2

II. 3-Hydroxy-2-methyl- propanoio Acid Lactone 4 19.8+0.1 62.5+1 113+3 10.8 -21.0 17.3

III. 3-Hydroxybutanoic Acid Lactone 4 4.8510.13 19.8+0.3 35.1+1 12.2 -18.6 17.8

IV. 3-Hydroxy-2,2- di me thy Ipr opanoi o Acid Lactone . 4 2.72+0.09 7.39+0.07 16.1+0.3 11.0 -24.2 18.2

V. 3-Hydroxy-3- methyIbutanoi c Acid Lactone 4 1,09+0.02 3.38+0.06 7.76+0.3 11.8 -23.1 18.7

VI. 4-Eydroxybutanoi c Acid Lactone 5 10.07+0.06 31.7+0.4 59.2+0.5 11.0 -21.7 17.5

VII. 4-Hydroxy-2- me thyIbutanoi c Acid Lactone 5 5.26+0.04 16.3+0.2 30.3+0.6 10.8 -23.6 17.8 Table IV (Cont’d.)

^ ’'2 , ^m±o.3) ^a±i) »pîî- Lactone Atoms -0.05 14.0° 16.1 25.0 (kcal./mole (e.u.) (kcal./mole)

VIII. 4-Hydroxypentanoic Acid Lactone 5 3.84+0.06 ------12.9±0.02 22.9+0.5 11.1 -23.2 18.0

IX. 4-Hydroxy-2,2- dimethyIbutanoic Acid Lactone 5 1.27+0.01 3.70+0.08 7.76+0.1211.0 -25.7 18.7

X. 4-Hydroxy-3,3- dimethyIbutanoi c Acid Lactone 5 1.22+0.01 3.78+0.03 8.24+0.02 11.7 -23.2 18.6

XI. 4-Hydroxy-4- methylpentanoio Acid Lactone 5 1.28+0.03 4.18+0.05 7.09+0.1210.4 -27.8 18.7

XII. 5-Hydroxypentanoic Acid Lactone 6 3 54^9------867+35 1401+19 8.2 -24.8 15.6

XIII. 5-Hydroxy-2- methylpentanoic Acid Lactone 6 156+6 — • 369+4 524+25 7.3 -29.7 16.2

ro VJT. Table IV (Cont'd.)

No« of Ring /)E^(+0.3) û^±l) Lactone Atoms -0.05° 14.0° 16.1 25.0 (kcal./mole (e.u.) (kcal./mole)

XIV. 5-Hydroxyhexanoio 6 180+3 436+12 661+8 8.0 -27.0 16.1 Acid Lactone

XV. 5-Hydroxy-2,2- dimethyIpe ntanoi o Acid Lactone 6 81.3+0.8 171+1 274+5 7.3 -31.0 16.3

XVI. 5-Eydroxy-3,3- dimethyIpentanoi c Acid Lactone 6 2.88+0.007 8.73+0.08 15.5+0 10.3 -26.7 18.3

XVII. 5-Hydroxy-5- methyIhexanoi c Acid Lactone 6 0.858+0.002 2.51+0.01 4.91+0.05 10.9 -26.8 18.9

XVIII. 6-Hydroxyhexanoic Acid Lactone 7 13.2+0.2 31.3+0.1 59,6+0.4 9.1 -28.0 17.5

XIX. 6-Hydroxyheptanoic Acid Lactone 7 5.14+0.08 12.1+0.2 22.110 8.7 -31.4 18.1 27 parameters are of similar orders of magnitude. In general substitution does not alter the gross effects of ring size on reactivity since the relative kinetic orderings remain the same when the rings are substituted comparably at various position. Notable exceptions to these generalizations occur in the 6-membered lactones containing gemrdimethyl groups in the 3- and 5-positions from the carbonyl group

(compoundsXH and XSII,Table 17), The rates of hydrolysis of these two lactones are decreased substantially from that of the parent lactone with concomitant increases in enthalpies of activation.

In general the relative rates obtained in this study are in agreement with those obtained under different conditions, by previous investigators (Table III, p. 18).

Saponification of Homologous TJnsubstituted Lactones

The results of saponification of unsubstituted homologous lactones, propiolactone through caprolactone, of the present study in 1,2- dimethoxyethane-water (1:1 by vol. at 25°) are summarized in Table 7 along with the data obtained previously in this laboratory (l5) for these lactones in 1,2-dimethoxyethane-water (2:1 by vol. at 25°) of different composition.

(15) C, A, Matuszak, Ph, D, Dissertation, The Ohio State University, 195?)•

It may be seen from the data of Table 7 that the order or rela­ tive rates (k£), relative enthalpies of activation ( AH*) and relative Table V

Effect of Solvent Composition on Rates of Saponification of Homologous Unsubstituted Lactones

l,2-dimethoxyethane-v.’ater (2*1 by vol.)* 1,2-dimethoxyethane-vfater (1*1 by vol.)**

Lactone o q ^2 q q ^ ^ q o kg q o i ? r fc -20.93 -5.36 -0.03 25.03 Aff 48^ -0.05 14.0 16.1 25.0 a C* Aff ^S

3-Hydroxy- propanoic Acid Lactone 1.68 7.66 12.71 16.8 12.8 -14.65 2 0 . 1 ---- 67.2 119 16.6 11.0 -20.6

4-Hydroacy- butanoio Acid Lactone 1.11 7.56 61.1 17.1 12.4 -17.18 31.7 59.2 16.9 11.0 -21.710.07

5-Hydroxy- pent anoi 0 A Acid Lactone 104 302 428 14.9 8.7 -22.68 O 0 % • - 867 1401 15.0 8.2 -24.8

6-Hydroxy- hexanoi c Acid Lactone 1.97 10.54 59.9 16.9 10.7 -22.87 13.2 31.3 59.6 16.8 9.1 -28.0

* C. A. Matuszak, Ref. 15. ** Results of present investigation.

(\ï CD 29 enthalpies of activation ( ^ S ’*') are the same in the two solvent systems j the k2 's (0°) are in the order 6 » i t > 7 '>5, the a H *s in the order

6 < 'I < ^ 'Z.hi and the a S *s in the order ij. > 5 > 7 > 6. It seems apparent therefore that the effects of ring size on reactivity as were discussed by Matuszak (see summary in "Theory and History," p. 8-13) are essentially the same in the solvents of different compositions.

A further comparison of the data of Table 1 indicates that the i|.-, 5- and 7-memibered lactones hydrolyze more rapidly, whereas the

6-membered lactone hydrolyzes more slowly in the solvent containing the higher concentration of water. Apparently there is an important difference in solvation of the 6-memibered lactone as compared to the it-, 5-, and 7-memibered homologs idiich may contribute to its relatively h i ^ reactivity.

As one of the tentative explanations for the fact that beta- propiolactone has a relatively high enthalpy of activation (the entropy of activation is relatively favorable) and is not hydrolyzed as rapidly as might be predicted by present theories of I-strain (18), it was suggested by Matuszak that the lactone is stabilized relative to its 5- and 6-membered homologs by virute of its unique possibility for ground state stabilization involving resonance structures such as

H I and 17;

<=> 4 - ^ H

n i n (39) 17 30

(39) (a) Resonance structure H I is similar to the "non-classical" cationic intermediate which has been postulated in certain carbonium ion reactions of cyclobutyl, cyclopropyl carbinyl and allylcarbinyl derivatives (J. Roberts and R. Mazur, J. Am. Chem. Soc., 73, 35U3 (1951)) (b) Additional structures such as:

y and I jnay also be written*

It is therefore pertinent to examine the data for l^-membered lactones studied in this investigation in an attençt to find substantiation of this postulate.

Evidence for possible quantum-mechanical stabilization of resonance structures such as type III cannot be ascertained sinply from the kinetic data for substituted beta-lactones. However, since contributing structures involving carbon-hydrogen hyperconjugation such as IV are not expected to be as inçortant in lactones con­ taining alpha methyl groups (ItO), it might be anticipated that

3-hydroxy-2,2-dimethylpropionic acid lactone (IV) would not exhibit stabilization similar to that of beta-propiolactone when cojiçared to analogously substituted 5- and 6-membered lactones.

(itO) It is usually accepted that carbon-carbon hyperconjuga­ tion is of lesser inçortance than carbon-hydrogen hyperconjugation although this point is the subject of debate. See for example, R. W. Taft, Jr., in M. S. Newman, St eric Effects in Organic Chemistry, p. 636 and H. C. Brown, J. Brady, W. drays on and W. bonner, J.-Am.'"^^ Soc., 1897 (19^7). In the present discussion it will be assumed 31 (following Taft) that carbon-carbon i^erconjugation is much less important than is carbon-hydrogen hyperconjugation. Brown postu­ lates however that carbon-carbon hyperconjugation is 80^ as effec­ tive as carbon-hydrogen hyperconjugation.

Comparison of the saponification data in Table V for 3-hydro:g-

2,2-dimethylpropionic acid lactone (IV), ^.-hydrozy-2,2-dimethylbutanoic acid lactone (IX) and ^hydroxy-2,2-dimethylpentanoic acid lactone (XV) indicates however that the same relatively high enthalpy of activation

= o

IVIX XV

11.0 kcal./mole 11.0 kcal./mole 7.3 kcal./mole persists when the alpha hydrogen atoms in the l;-membered lactone are replaced by methyl groips. Therefore, if the postulate is accepted that carbon-carbon hyperconjugation is of considerably less importance than is carbon-hydrogen hyperconjugation, it appears that resonance form IV (p. 29) cannot be an impoirtant contributor to the relatively large activation energies of saponification of it-merabered lactones.

The kinetic effects in reactions of small ring compounds have often been explained on the basis of I-strain by taking into account only differences in strain involved in deformation of the normal bond angles of a ring in its ground and transition states (18). Such a picture cannot be totally realistic because in all probability the 32 rings are not conçrised of deformed normal bonds but rather of

intermediate hybrid bonds. Thus, cyclopropanes exhibit unsaturated

character in both their physical and chemical properties.(1:1).

(1(1) For a review of the chemical and physical properties of cyclopropanes and cyclobutanes, see E. Vogel, Fortschr. Chem. Forsch., 3, li30-502 (1953).

In order to account for the unsaturation and external H-G-H bond angles of 118° in cyclopropane, it has been suggested (1(2) that the hybridization of the carbon atoms in cyclopropane is sp^ rather than the expected sp3 types, with one of the 3 sp2 bonds on each carbon atom directed toward the center of the ring, and the lone "p" orbital directed toward the periphery in the plane of the ring;

(1(2) A. Walsh, Trans. Faraday Soc., 179 (191(9).

This representation of cyclopropane offers an explanation for the external H-C-H bond angle and the unsaturated character, but in

addition implies a weakening of the carbon-carbon bonds because of the increase in their "p" character and thus gives a quantum- mechanical interpretation of "strain" (1(3). The structure given to

cyclopropane is obviously extreme, but points out the necessity 33

(Ji3) The. same results, for the bond strengths of cyclopropane have been derived by considering the internal angles to be 10i).°, instead of the 60° angles required by the 3-membered ring; A. Coulson, and W. Hoffitt, J. Chem. Phys. l$j 1$1 (I9k7); Phil. Mag., ItO, 1, ( W ) . ■" “ to consider hybridization other than ordinary sp^ in order to account for its properties.

By applying similar arguments it is expected that a it-membered ring will exhibit unsaturated character as does cyclopropane but to a lesser degree. Cyclobutane undergoes certain of the addition reactions of cyclopropane under relatively vigorous conditions (lil), add there is spectral evidence which has been interpreted to indicate delocalization of electrons in the i^-membered ring (1^4^).

(liU) J. Wren, J. Chem. Soc., 2208 (1956).

Applying such concepts to beta-propiolactone (U5) it would be

(U5) It has been postulated by Walsh (ref. k2) that ethylene oxide is hybridized in much the same manner as cyclopropane. The presence of a ring oxygen atom as in the lactone therefore does not alter greatly the theoretical considerations. expected that the carbonyl oxygen atom could enter into the delocali­ zation of the li-membered ring in much the same manner as with the methy­ lene group in ketene;

6> ® CHg “ C = 0 f-* CIÎ2 — C S 0 (lj.6) « 3h

(U6) Although resonance of this type m i ^ t not be expected to be important, the-lengthening of the C-C distance from 1.33a as in ethylene to 1.35 A in ketene and the shortening of the C-0 distance from 1.22 A in ketones to 1.17 i in ketene (part of this may be a result of hybridization differences) attests to a contribution from the charge separated form. The resonance stabilizàtion in carbon dioxide is analogous to that discussed for ketene; 0=C=0 4—» 6-0=0 L. Pauling, Nature of the Chemical Bond, Cornell University Press, Ithaca, New ï'ork, 1%^, p. 1^6.

This molecular orbital description of beta-propiolactone is similar to the valence bond structure III (p. 29) proposed previously to account for the apparent stability of the It-membered lactone.

Valence bond structures indicating carbonyl strengthening may be written as:

o®

An additional factor tending to strengthen the carbonyl bonds of beta-propiolactone relative to the 5-membered lactone is the possibility for increased overlap of the carbonyl group with the ring oxygen atom. The C-O-C bond angle in the h-membered lactone is very nearly 90°; precisely the angle required by oxygen in an unhybridized state. Since the carbonyl group and the ring oxygen atom must describe a plane, maximum overlap of "p" orbitals will be anticipated (1:7); 35

(kl) (a) Although the normal external angle of the carbonyl carbon is extended from 120° toabout 135°> the p orbital which is perpendicular to the plane of the sp2 orbitals, is still parallel to the p orbital on adjacent oxygen, (b) S. Searles, M. Tarares, and G. Barrow, J. Am. Chem. Soc., 75, 71 (1953) have come to the opposite conclusion based on the relative basicities of the ii-, 5- and 6- membered lactones as measured by hydrogen bonding. The uncertainty of the center of basicity in lactones however complicates their interpretation.

In the 5-raembered lactone, with internal bonds between 90 and

120°, the orbitals utilized by the ring oxygen atom are expected to be hybrids approaching sp3 hybridization in much the same manner as the oxygen atom in water (U8). The ordinary p orbitals of the ring

(1:8) C. Coulson, Valence, Claredon Press, Oxford, 1952, p. 209. oxygen atom therefore will have a certain amount of "s" character.

This hybridization will result in a decrease in "p" overlap between the ring oxygen atom and the carbonyl group because of a difference in anti-symmetry of the ordinary "p" orbitals of the carbonyl group and the hybridized orbitals of oxygen.

These factors of (1) quantum-mechanical stabilization of a l:-raerabered lactone and (2) difference in ring oxygen hybridization between it- and 5-membered lactones possibly tend to stabilize the ground state of the it-raembered lactone relative to the 5-membered homolog and may account for the relatively h i ^ enthalpy of activa­ tion noted in hydrolysis of it-raembered lactones. 36

Since the transition state for saponification of lactones is expected to be close in structure and energy to intermediate, in which resonance is relatively unimportant, stabilization by factors (1) and

(2) above is insignificant in the transition state relative to ground state.

It is not implied that these factors will necessarily be dominant in reactions of 3- and ii-membered rings, but only that they should be considered along with the usual concept of I-strain to obtain a more realistic picture of reactivities of small ring com­ pounds .

Effect of Methyl Substituents on Reactivities of Lactones.

In general methyl substitution does not seriously affect the relative reactivities of U- through 6-membered lactones. The gross effects inherent in the particular lactones because of ring size remain dominant in determining relative reactivities of the substi­ tuted lactones studied. There are, however, certain magnifications of effects and exceptions to the above generalization which will be discussed. A similar conclusion appears to exist in the 7-membered lactones; however, the data from the present study are too limited to allow an inclusive generalization. 37

Substituted U-Eienibered lactones

3-Hydroxy-2-methylpropanoic acid lactone, (II) (h9)f exhibits

=o

II 19.8

(U9) All compound numbers in this section refer to Table 17. Numbers below formulas are rate constants (k2 ) in l./m. x min. at 0°. atjpicâl behavior for an alpha substituted lactone; its methyl group has no apparent effect on the rate constant (k20 ° = 19.8 l./m. x min.) enthalpy (

-21.0 e.u.) when conpared to the parent, unsubstituted lactone (I, beta-propiolactone k2 *= 20.1 l./m. x min., = 11.0 kcal./mol.

4 = -20.6 e.u.). The lack of an apparent steric effect of the methyl group (eclipsing strain in the reaction intermediate may be expected) may be partly rationalized on the basis that (1) the carbonyl group in the li-merabered ring is relatively exposed because the adjacent ring atoms are tied back and (2) the ring atoms of the lactone hydrolysis intermediate are not planar and thus conformations of the substituent atoms are not seriously eclipsed. It is not appar­ ent however why the rate of saponification of this lactone reflects 38 neither the usual steric nor inductive effects of a methyl group

(50).

(50) The relative rates of saponification for ethyl propionate and ethyl isobutyrate in water at 23° compared to ethyl acetate are O.J4.70 and 0.100 respectively; C. K. Ingold, Structure and Mechanism in Organic Chemistry, Cornell University Press, ïthaca. New York, 1953, p. ?5b.

The remaining substituted It-membered lactones, 3-hydroxy- butanoic acid lactone (HI), 3-hydroxy-3-metbylbutanoic acid lactone

(7) and 3-hydroxy-.2,2-dimethylpropanoic acid lactone (17) exhibit deceleration as e:q)ected on the basis of inductive (3l) and steric

= 0 =0 = 0

III 17 7 li.85 2.72 1.09

(51) It has been shown that the relative ordering of inductive effects of alkyl substituents in the position adjacent to the alkoxyl oxygen atom in esters is the same as alkyl substituents in the position adjacent to the carbonyl group (R. ¥. Taft, Jr. in M. S. Newman, Steric Effects in Organic Chemistry, Chapter 13). The relative order of tihe raa^itude of inductive effects in the two positions is not clear. effects. An inportant difference exists however in the activation energies of the alpha-gem-dimethyl lactone and the beta substituted lactones. 3-Bydroxybutanoic acid lactone and 3-hydroxy-3-methyl- 39 butanoic acid lactone have activation enthalpies of 1.2 and 0.8 kcal./mole, respectively, hi^er than 3-hydroxy-2,2-dimethylpropanoic acid lactone (these enthalpy differences are believed to be beyond the experimental errors). In addition, it is significant that the beta-gemrdimethyl group is 2.5 times more effective in retardation than is the alpha-gei&-dimethyl group. It is unlikely that the larger beta-dimethyl deceleration results primarily from an inductive effect since the methyl groups in the alpha position are expected to have a greater electron-donating effect on the carbonyl carbon than do the beta methyl groups.

A significant effect may result from 1,3 interactions between the two oxygen atoms in the 1-position of the intermediate (or more properly, the rate-determining transition state) and the beta methyl groups (8). Such a steric effect is expected to be important because of the proximity of atoms in the 1,3 positions in l;-membered rings (52) and because of the probable non-planarity of the Ji-membered■ lactone intermediate (53). On the basis of a planar model for the

(52) On the basis of a planar model and 9Q0 angles for cyclo- butane the 1,3 interatomic distances of ring atoms are approximately 2.18 L

(53) Cyclobutane has been shown to be nonr-planar; J. D. Dunitz and V, Shomaker, J. Chem. Phys. 1703 (1952). Although the presence of an oxygen atom in the ring of the lactone might be expected to increase planarity of the intermediate, the effect of non-bonded interactions may be sufficiently large to retain non­ planarity. i|0 intermediate (Structure A) the steric effects are expected to be greater for alpha- rather than beta-gem dimethyl groups.If however the reaction intermediate is non-planar (less planar than the parent lactone) (Structure B) it is possible that 1,3 non-bonded interactions may become more inportant than the sum of the inductive effects and the steric effects of 1,2 interactions.

A (b> a) B (b< a)

An alternate explanation may be considered based on the direc­ tion of approach by hydroxide ion as was discussed by H. K. Hall, Jr. in relation to the saponification reactivities of lactones as com­ pared to acyclic esters (see discussion of the effect in "Theory and

History," p. 6). According to this argument the energy involved in approach of a hydroxide ion to a carbonyl group at an angle of about

180° will be less than when perpendicular (axial). In a it-membered lactone such directed approach will require that the hydroxide ion attack along the plane of the beta carbon atom. Methyl groups in the beta position therefore would be expected to hinder the approach to a greater extent than substituents in the alpha position. la consequently lowering the rate of hydrolysis of 3-hydroxy^3-methyl- butanoic acid lactone relative to 3-hydroxy-2,2-diaiethylpropanoic acid lactone.

This postulate of backside approach (approximately in the carbonyl plane) by hydroxide ion in which the unfavorable electro­ static repulsion from the lone pair atom dipole of oxygen is avoided requires that the transition state for saponification of esters and lactones reflect prominently the structures of the parent reactants.

The structures of the transition states under these circumstances will be "close" to reactants and imply that there is only weak bonding of the attacking hydroxide ion in the rate-determining activated complexj the transition states will thus be expected to have marked trigonal character. For there to be marked steric effects in hydrolysis of esters and of lactones in which the bonding in the transition state is weakly developed, the steric factors will have to be very large and operate over fairly long distances.

It is very unlikely however that this is the ease. The highest point in the activation energy curve (fairly large enthalpies of activation, = 7-12 kcal./mole) is expected to be "close" to intermediate (structure different from reactants) since formation

of this intermediate is endothermie and involves a large activation energy. The facts that steric effects play very large roles in saponification of esters and that very marked 1,3-steric inter­ actions are involved in saponification of substituted 6-membered lactones are best explicable on the basis that the structures and h2 the energies of the rate-controlling transition states are close to reaction intermediates. It is the present author’s belief there­ fore that interpretation of these steric effects should be made on thé basis of the energy of a transition state in which incipient tetrahedral bonds are highly developed rather than on an electrical basis in which substituents on an ester or a lactone retard or detour approach of the attacking base in a back-side direction at an 180° angle to the plane of the carbonyl group (Bh).

(5U) Hall has used as an argument for the postulate that rearward attack on a carbonyl group by hydroxide ion is preferred that 6-oxabicyclo C3:2:ll octane-7-one is saponified more rapidly than is 2-oxabicyclo C2:2:2J octan-3-one. It is of significance that the fact that the latter lactone hydrolyzes more slowly than does the former can be explained simply on the basis of the effects of 1,2- and 1,3- nonbonded interactions in the reaction intermediates. It may also be expected that attack by hydroxide ion perpendicular to the carbonyl plane would be energetically more favorable than rearward attack on the carbonyl group.

Substituted 3-membered lactones

lt-Hydroxy-2-methylbutanoic acid lactone (VH) and h-hydroxy- pentanoic acid lactone (VIH) have similar relative reactivities;

VII vin 5.26 3.8U h3

the differences in their enthalpies and entropies of activation are

very small. Since the inductive effect of the alpha methyl group is

expected to be greater than that of an omega methyl group, it may be

that the similarity in reactivities is a result of a greater steric

effect from the omega methyl group than the alpha methyl group.

This postulate will be subsequently developed further in discussion

of the possible geometry and conformations of trigonally and

tetragonally-substituted ^merabered rings.

U-bydroxy-3.3~dimethylbutanoic acid lactone (X) undergoes basic

hydrolysis at a rate very similar to that of L-hydroxy-2,2-dimethyl-

butanoic acid lactone (IX). In hydrolysis of the 3,3-dimethyl

lactone, the retardation is almost entirely steric if inductive

V

"O

X IX 1.22 1.27

effects through space are minimal (as expected). It appears therefore that the magnitude of steric retardation by a gem-dimethyl group in

the 3-position is essentially equivalent to the sum of the inductive

and steric effects of alpha-gem-dimethyl groups. This steric effect

is explicable on the basis of the formation of an intermediate whose ring atoms are non-planar in saponification of 5-membered lactones (55), là

(55) K. s. Pitzer, Science, 101, 6?2 (19h$) postulates non- planarity of cyclopentane rings resulting from bond opposition of atoms on adjacent methylene groups. If the hybridization of the ring oxygen in the 5-membered lactone hydrolysis intermediate is the same as in water (C. Coulson, Valence, p. l6o), the angle requirement of oxygen will be very nearly equal to that for sp3 carbon. In addition the p-electrons of the ring oxygen atom will be expected to have a similar effect on non-bonded interactions as does a methylene group (H. Brown, J. Brewster and H. Shechter, J. Am. Chem. Soc., 76, U67 (I95b). Therefore the 5-membered lactone intermediate is expected also to be non-planar.

Depending on the degree of non-planarity of the ring atoms, the non­ bonded 1,3-interactions may be greater than those in the 1,2 position in much the same manner as was indicated for k-membered lactones

(p.'^o). The present data support the postulate of non-planar reaction intermediates in saponification of 5-membered lactones.

Comparison of the data for ii-hydroxy-I|.-methylpentanoic acid lactone (XI) with that of i|.-hydroxy-2,2-dimethylbutanoic acid lactone

(IX) (k20 °, 1.28 and 1.27 l./m. x min. respectively, and

^ within experimental error) for further information concerning the relative magnitudes of 1,2 and 1,3 non-bonded interactions is

XI IX 1.28 1.27 inconclusive because of the added complication of inductive effects of methyl groips in the omega position as well as in the alpha position. Substituted 6-meiabered lactones

The two mono-substituted 6-membered lactones, 5-bydroxy

-2-methylpentanoic acid lactone (XIII) and 5-hydroayhexanoic acid lactone (XIV) hydrolyze at nearly equal rates (kgo^, 3-56 and 180 l./m.

X min. respectively); the omega substituted lactone is somewhat slower.

xm XIV 156 180 The corresponding 5-membered homologs also hydrolyze at similar rates, but the alpha-substituted lactone is the slower. The differences in rates in each series however are possibly too small to warrant extensive theoretical conclusions. The inductive and steric effects ejipected to be operative in these conçounds are brought out more clearly in the gem-dimethyl lactones discussed below.

A possible ittportant effect is noted in the kinetic parameters for 5-hydro%y-2,2-dimethylpentanoic acid lactone (XV) and 5-hydro%y-2,- methylpentanoic acid lactone (XIH), In both lactones there are

XV xin 81.3 156 46 significant decreases in activation enthalpies compared to the parent lactone; éaS*, -0,9 kcal./mole in each case. There appears to be an added driving force for formation of the hydrolysis intermediate over that for the unsubstituted lactone (k^o^ = 354 l»/jn* x rain.) even thou^ the overall effects of alpha methyl groups are decelerating.

The rapid rate of hydrolysis of a 6-membered lactone in relation to

4-j 5- and 7-raembered lactones has been attributed to relief of eclipsing interactions resulting from introduction of a trigonal atom in a 6-membered ring. Formation of the saponification inter­ mediate allows cojiplete staggering of groups and electrons on ring atoms adjacent to the carbonyl group (see "Theory and History, p. 10). It is possible that the decrease in activation enthalpy lactones XV and XIII from that of the parent lactone, arises from greater eclipsing strain in the lactone when hydrogen is replaced by a larger group. The greater relative strains in the ground states of the substituted lactones results in greater driving forces for formation of staggered, non-eclipsed intermediates than in the case of the parent lactone.

The rate of hydrolysis of 5-hydroxy-2,2-dimethylpentanoic acid lactone (XV) is approximately one-quarter that of the unsubstituted

XV 81.3 it?

6-menibered lactone. This retardation is not very large and is a result of inductive and steric effects of the alpha-gent-dimethyl

group.

By far the largest effects observed in the present study are

illustrated by comparing the rate of hydrolysis of the unsubstituted

6-membered lactone with those of $-hydroxy-3.3-dimethylpentanoic

acid lactone (XVI) and 3-hydroxy-3-methylhexanoic acid lactone (XVII).

Introduction of the gem-dimethyl groups lead to a deceleration in

hydrolysis of 120- and UOO-fold respectively. Undoubtedly steric

XVI XVII 2.88 0.838

strain resulting from 1,3 and 1,3-interactions in the reaction inter­

mediates is the principal cause of these effects (56). 1,3-Interac-

(36) Both lactones are substituted 3 atoms removed from the carbonyl group.

tions of this type have been noted frequently in saturated 6-membered

rings containing only carbon. The quantitive effects (3?) for carbon

rings are indicated by the equilibrium constants of reactions of a

series of substituted cyclohexanones with hydrogen cyanide (Table VI). h8

(57)0. Wheeler and J, Zabicky, Can. J. Chem., 656 (1958); Chem. and Ind., 1388 (1956).

Table VI

Equilibrium Data for Reaction of Ketones and Hydrogen Cyanide*

[HCN] C)C=0J

Relative Equi­ Ketone p. / ^ C N J librium Constant

Cyclohexanone 5.91 (1.00) 2 -Methylcyclohexanone 10.7 1.8 3-Methylcyclohexanone 5.5 0.93 ii-Methylcyclohexanone 3.15 0.53 2,2-Dimethylcyclohexanone 9.2 1.6 cis-315-Dimethylcyclohexanone 25.7 1*1* 3,3-Dimethylcyolohexanone 176 30 3,3,5-Trimethylcyclohexanone 22h 38 3,3,5,5-Tetramethylcyclohexanone 1*690 800

^Measured in 95^ ethanol at 25°.

These thermodynamic data are quite sensitive to substitution in the 3-position of cyclohexanone. The kinetic data obtained in the present study for saponification of 6-membered lactones hcfwever are considerably more sensitive to such substitution (see Table I H , compounds XVI and XVIl).

1,3- and 1,5-Interact ions in cyclohexané systems are due to the geometry of the 6 -membered ring. The cyclohexahe ring is non- planar and essentially strain free. In the preferred chair form (58) h9

(58) W. Daiiben and K. Pitzer in M. S, Newman, Steric Effects in Organic Chemistry, p* 13-23.

the hydrogen atoms on adjacent carbon atoms are staggered, resulting

in two different types of bondsj those in approximately the same plane as the ring (equatorial) and those extending above and below the plane

(axial). A further consequence of this conformation is that sub­

stituents in 1,3-diaxial positions are closer than are substituents

in 1,2-positions (axial or equatorial) (59).

(59) The calculated C-C interatomic distances for alkyl groups attached to the chair conformation of cyclohexane are: le:2e or let2a 2.96 S.; la:2a, 3.88 Sj la:3a, 2.51 -Sj W. Klyne, Progress in Stereo­ chemistry, Vol. 1, Academic Press Inc., 195U, p. i;U. ~

«

Preferred Chair Conformation of Cyclohexane (a=axial bonds, e=equatorial bonds)

Consequently steric effects between axial groups in 1,3-positions are

greater than equatorial-equatorial or equatorial-axial interactions

in 1,2-positions. It is expected that a single substituent in the

3-position will not exhibit any significant 1,3-interaction since it most likely will occupy the preferred equatorial position and thus 50

minimize its interaction with either substituent at the 1- position.

The results obtained for saponification of 6-membered lactones

having gem-dimethyl substituents in the 3 and 5-positions (confounds

l6 and 17) are analogous to those exhibited by similarly substituted

cyclohexahe systemsj it thus appears that the geometrical changes

in conversion of a 6-membered lactone to its saponification inter­

mediate are similar to that for conversion of a trigonaHy-substi-

tuted cyclohexane ring to a tetragonal derivative.

The steric effects observed in saponification of substituted

6-membered lactones are similar to those exhibited by analogous

open-chained esters. Since the geometry of the saponification inter­

mediate of a 6-membered lactone is similar to that of an open-chain

ester exhibiting 1,6-coiling interactions, it is expected that

steric effects in the two systems will be similar. The 1,3-ioten­

action in hydrolysis of a 6-membered lactone is thus nothing more

than a special case of hindrance on the 6-position in hydrolysis of

esters (60 ) (retardation arising from increasing the nunber of

atoms in the 6-position in hydrolysis of esters thus results

primarily from 1,3-interactions in the reaction intermediates).

(60) Although there are no data for saponification of direct­ ly related esters, estérification of similarly substituted acids, which is expected to show analogous steric effects, indicates rela­ tive reactivities of the same order of magnitude as is found for saponifioation 1,3-substituted lactones studied in this investiga­ tion; M. S. Newman, Steric Effects in Organic Chemistry, p. 205. 51 In 6-membered lactones as with the smaller ring homologs, the 1,3-interactions show up largely as effects; increases in activation enthalpies for 5-hydrdxy-3,3-dimethylpentanoic acid lactone and 5-hydroxy-5-methylhexanoic acid lactone are

2.1 and 2.7 kcal./mole respectively, cojiç>ared to the unsubstituted lactone.

The approximately 3-fold difference in rates between the beta-gem-dimethyl-6-menbered lactone and the omega-geminal sub­ stituted 6-membered lactone (k^o° 2.88 and 0.858 l./m. x min. respectively) may be interpreted as additional deceleration due to the inductive effect of the methyl groups in the _5-position.

Substituted 7-membered lactones.

The only substituted 7-membered lactone studied in the present investigation was 6-hydroxyheptanoic acid lactone (confound 19).

This lactone exhibits approximately a 2.5-fold decrease in saponifi­ cation rate when compared to the parent 7-membered lactone (compound

18). This deceleration may be due entirely to the inductive effect of the methyl group or to a combination of inductive and steric effects. It will be noted that the relative deceleration compared to the 7-membered lactone (2.57) is essentially the same as occurs in the analogous omega-substituted 5-merabered ring (2.62) compared to its parent lactone (6l). (61) The geometiy of the 7-membered ring is believed to be very similar to that of the $-membered ring. See H, C. Brown, J. Chem, Soc., 12i|8 (19^6), M. S. Newman, Steric Effects in Organic Chemistry, p. 122-123, 238, and N. AHinger, A.C.S. Abstracts of Papers, 131st. meeting, Miami, Fla., 1937, 27-0.

Relative Effects of Substituents on the Saponification of Lactones of Various Ring Sizes

Additional information from the present study is obtained by comparing the ratio of rates of basic hydrolysis of a parent lactone to its substituted lactone with the ratio of the corresponding lactones of a different ring size. In these comparisons inductive effects of the methyl groups will be presumed to be constant as the ring size is varied. Resonance in parent and substituted rings is also assumed constant. The absolute and relative rates of hydrolysis are summarized in Table V U .

The inportance of a single methyl substituent, (adjacent to ether oxygen) on possible 1,3-interactions in the reaction inter­ mediate as ring size is varied is revealed by comparison of the relative reactivities of the corresponding unsubstituted lactone with 3-hydroxybutanoic acid lactone (HI), i;.l3, (62), l;-hydroxy- pentanoic acid lactone (VIII), 2.62, 3-hydroxyhexanoic acid lactone

(XIV), 1.97, and 6-hydr oxyheptano ic acid lactone (XIX), 2.37 (63).

(62) All compound numbers in this section refer to Table VCI. Numbers below the formulas are relative reactivities. 53

Table T U

Absolute and Relative Rates of Saponification of Homologous, Substituted Lactones*

k2 , unsubstituted lactone Acid Lactone ^2^ ^ k2 , substituted lactone

I. 3-Hydroxpropanoic 20.1 (1.00) II. 3-Hydro%y-2-methylpropanoic 19.8 1.02 III. 3-% d r oxybutano ic 1.85 a.15 17. 3-Hydroxy-2,2-dimethylpropanoic1 2.72 7.k0 7. 3-Hydroxy-3-methylbutano ic 1.09 18.1; 71, Ii-Hydr oxybutano ic 10.07 (1.00) 711. It-Hydroxy-2-methylbutano ic 5.26 1.91 Till. ij-Hydroxypentanoic 3.81; 2.62 IX. ii-Hydroxy-2,2-dimethylbutanoic 1.27 7.93 X. l^-Hydroxy-3 , 3-dimethylbutano ic 1.22 8.25 XI. U-Hydroxy-li-methylpentanoic 1.28 7.86 X U . 5-Hydroxypentanoic 351 (1.00) XIII. 5-Hydroxy-2-methylpentanoic 156 2.27 XIV. 5-Hydroxyhexanoic 180 1.97 XV. 5-Hydroxy-2,2-dimethylpentanoic 81.3 h.35 Ï7I. 5-^ydro:qr-3,3-dime thylpentanoic 2.88 123 XVll. 5-Hydroxy-5-methylhexano ic 0.858 X7III. 6-Hydroxyhexano ic 13.2 (1 .00) XIX. 6-Hydroxyheptanoic 5.11; 2.57

^solvent: 1,2-diraethoxyethane-water, 50:50 by vol. (25°) tenç).: -0.05°; base: sodium hydroxide. 5k

2=0

III VIII U.15 2.62

XIV

1 . 9 7

(63) Since each lactone is conpared to the parent lactone of its own ring size, the values indicate the relative effect the methyl group has in that particular sized ring; the larger the value of the ratio, the greater the deceleration in hydrolysis.

Although the relative differences are small, on assuming that

solvation effects are essentially constant, the results indicate

that the net steric effects of a single methyl group (1,3-inter­

action) for reaction of lactones increases in the following order

for the various rings: l+> 3=7> 6. On the premise that inductive

effects are constant, the 1,3 steric interaction of a methyl group

■ decreases with increasing ring size (excepting the 7-membered lac­

tone which is nearly equal to that of the 5-membered lactone). This ordering is explicable on the bases of the geometries of the lactones and of the rate-determining transition states as reflected by the presumed structures of the'tetrahedral reaction intermediates. A mono-methyl substituent in an omega position will result in a greater 1,3-interaction in a U-membered lactone inter­ mediate than in the larger ring homologs because of (1) the rela­ tively short interatomic distance and the substituted ring atom from the developing tetragonal center (2) the greater planarity of the ring of the U-membered lactone reaction intermediate and (3) the relatively large axial character of the methyl substituent.

The 1,3 interatomic distances in the 5- and 6-membered lactones are expected to be similar if the ring atoms are (essentially) planar. The relative planarity (puckering) of k-j and 6-membered lactone intermediates are expected to be quite different however.

The reaction intermediate from the J^-raerabered lactone is essentially planar, that from the 6-membered lactone is expected to be highly non-planar and have the geometry of a chair form of a 6-membered ring; the non-ring bonds of the 6-membered lactone hydrolysis intermediate may thus occupy axial and equatorial positions (see p. 1 0 ). A single 3-methyl substituent in the 6-membered lactone intermediate will prefer an equatorial position.

The ring system of the reaction intermediate from a S- membered lactone is expected to be sli^tly puckered or possibly planar; the bonds attached to the tetrahedrally substituted inter- 56 mediate are '•quasi” axial and equatorial or are identical and intermediate between axial and equatorial for these geometries.

Therefore the result of differences in non-planarity in reaction intermediates in the order ii^5<6 is to allow the single methyl group to become progressively farther removed from the closer group in the l-poisition in the order 6 (see figure below)j this consequently results in relative deceleration from 1,3-interactions with single substituents in the order it >5?6.

Relative Conformations of k~, 5- and 6-Membered Rings

Conversely, substituents in the 1,3-diaxial positions in a chair-shaped 6-membered lactone intermediate are closer than in the corresponding l,3-”quasi'' diaxial positions in the puckered saponification intermediate from 5-membered lactones. One of the two methyl groups must be axial or "quasi” axial in the saponifica­ tion intermediate. The relative rates of hydrolysis are: 3-hydroxy-

3-methylbutanoic acid lactone (V), 18.i^, lj-hydroxy-l;-methylpentanoic 57 acid lactone (XI), 7.86 and 5-hydro3cy-5-raethylhexanoic acid lactone

(XVH), ml).. In these systems therefore the overall effects of

1,3-interactions increase in the order 6 » k > 5 > The change in order of hydrolysis of these 5- and 6-membered lactones is predicted on the basis of the geometrical considerations discussed previously.

The relative ordering of the ii- and 6-membered lactones suggests that the distance between 1,3-diaxial groups in the 6-membered ring intermediate is even less than that in a L-membered ring intermediate.

=o

V XI xvn 18.k 7.86 lOli

Since the actual geometry (degree of non-planarity, conformation of substituents) of the li-membered ring intermediate is uncertain, the distance between groiçs in the 1,3 positions cannot be calcu­ lated accurately.

A further comparison illustrating the relative importance of non-bonded interaction in 1,2-positions as a function of ring size may be seen in the hydrolysis of 3-hydroxy-2,2-dime thylpropanoic acid lactone (IV), L-hydroxy-2,2-dimethylbutanoic acid lactone (IX) and 3-hydroxy-2,2-dimethylpentanoic acid lactone (XV). The relative 58 effects of 2,2-gem-dimethyl groups in retarding hydrolysis of h-,

5- and 6-membered lactones are: 7.i+0, 7.93 and k-3S respectively

< =o

IV H XV 7.U0 7.93 lt.35

(5 6). That the 2,2-dimethyl-5-membered lactone exhibits the greatest relative deceleration is in agreement with the previous discussions of the geometries and eclipsing of groups on adjacent atoms in 5- and 6-membered lactones and their reaction intermediates

(for similar arguments in 5- and 6-membered carbon rings, see

"Theory and History," p.io). Since formation of the hydrolysis intermediate of this 5-membered lactone involves conversion of the trigonal carbonyl group to a tetrahedral center, additional eclipsed interactions (atom-atom and atom^electronic) are introduced. Since a 5-membered lactone intermediate is expected to have all of its substituents essentially eclipsed and the vicinal groups relatively close, its related transition state should reflect greatly the effects of alpha-gem-dimethyl grorç)s. The relative reaction rate least affected is that of the 6-membered lactone; this effect may 59 be rationalized on the basis that an eclipsed 6-membered lactone

undergoes conversion to a reaction intermediate in which there is

staggering of all adjacent groups.

The position of the i|-merabered lactone in the present congsari-

8on is possibly of considerable theoretical significance. The

relative reactivities (large deceleration) appear to indicate that

non-bonded interactions are of magnitude conçjarable to those involved

in reaction of 5-membered lactones.

It is not apparent why the alpha-mono-methyl conçounds, 3-hydroxy-

2-methylpropanoic acid lactone (II), i(.-hydroxy-2-methylbutanoic acid

lactone (VII) and 5-hydroxy-2-methylpentanoic acid lactone (XIII),

do not show the same relative ordering of relative reactivities when compared to their parent lactones j the order is

/ =o

n VII x m 1.02 1.91 2.27

Entropy Effects in Saponification of Lactones

The entropies of activation for homologous ring lactones, as

indicated in Table IV, become in general systematically less favor- 60 able (more negative) as the size of the lactone ring increases. The entropies of activation are -20.6, -21.7, -2ij..8, and -28 e.u. for the parent ii-, 6-, and 7-membered lactones respectively.

The trend observed is in general agreement with the following interpretations. (1) Based on the transition state theory of kinetics, the entropy term approximately represents the relative ordering and freedom of atomic motions of reactants in the ground and transition states; the more highly ordered the system, the less favorable the enthalpy.

Bimolecular reactions are expected to show negative entropy changes, since the reactants (and sometimes the solvent) are more highly ordered in the transition state than in the ground state.

Changes in rigidity of cyclic molecules in ground and transition states will also be manifested in the entropy factor. The ordering of entropies of the present study (more favorable: i;>5>6>7) may thus indicate that there is a larger change in rigidity between ground and transition states for saponification of lactones as ring size increases. This ordering of rigidity change may be rationalized on the basis that the smaller the ring, the more rigid is the lactone; the smaller the trigonally substituted r^g, the greater the relative introduction of flexibility in conversion to the tetrahedral transi­ tion state as a result of diminished angle strain (diminished bond distortions) and more favorable bond hybridization. (2) It may be that the larger ring saponification intermediates allow more solvent molecules to solvate the reacting center than do the smaller ring 61 intermediates, thus causing a greater change in ordering of solvent from ground to transition states. This effect would also contribute to the observed ordering of entropy of I4. 7^ ^6 ^ 7.

Also, because of the great polarizability of the smaller ring lac­ tones solvation of the lactones may decrease with increasing size, thus leading to the above ordering. (3) An alternate but perhaps less revealing interpretation may be based on the collision state theory of kinetics; that is, the greater the probability of effec­ tive collision, the more favorable the entropy, (roughly comparable to PZ in the collision state theory). On this basis, the ordering of entropies of activation of lactones will reflect the greater

•probability that hydroxide ion will collide with the carbonyl group in the required manner for effective reaction rather than with some other portion of the molecule. In general the smaller the ring size of the lactone, the greater will be the probability for attack at the carbonyl group; the ordering in entropies for ring size is thus in agreement with By this argument, it is expected that alkyl substituents, particularly near the reaction site (adjacent to the carbonyl group) will further reduce the proba-- bility of effective collisions with molecule. The entropy values for the substituted lactones in Table 17 are in general agreement with this prediction. 62

Summary

The important conclusions arrived at from the above discussion may be summarized as follows: (1) in general the effects of mono- methyl and gem-dimethyl substituents are not sufficiently great to be dominant over effects of ring size in determining the relative saponification rates of lactones 7 ? 5)j the 3,3- and 5j5- dimethyl-substituted 6-membered lactones are notable exceptions since they exhibit large deceleration because of the magnitude of

1,3-diaxial steric interactions resulting from the chair conforma­ tion of the tetrahedrally substituted lactone intermediate, (2) alpha-mono-methyl substitution causes deceleration in the order

6'>5’?Uj alpha-dimethyl substitution causes deceleration in the order ^3 It > 6 as expected on the basis of the relative inportance of 1,2 eclipsing interactions in the various size lactone inter­ mediate, (3) the enthalpies of activation of both the alpha mono-methyl and alpha dimethyl substituted 6-membered lactones are more favorable than that of the parent lactone as a result of added eclipsing interaction in the lactone which is removed in the rate- controlling transition states, (1+) the steric effects (ii>5~7>6 for omega mono-methyl substituents and 6»i;>5 for beta and omega gem-dimethyl substituents) are determined largely by the differences in conformations of the lactones and their rate-determining transi­ tion states for formation of the lactone saponification intermediates; electrical effects are difficult to estimate quantitatively since 63

they usually operate in conjunction with steric effects, (5)

substituted beta-lactones possess inherent stabilities similar to

that of the parent ij.-membered lactone; it is possible that the 1^- membered lactones exhibit appreciable stabilization as a result of

delocalization, (6) entropy effects (less favorable with increasing ring size) are explicable on the basis of relative rigidity changes

in the different size rings in conversion of the trigonally substi­

tuted lactones to the tetrahedrally substituted lactone saponifi­

cation intermediates, (7) the structural and conformational changes

in saponification of ^ through 7-membered lactones are analogous to

those in conversion of trigonally substituted carbocyclic rings to

their tetrahedral derivatives, (8) the 6-membered lactone is unique

in that its rate of saponification decreases in going to a solvent

of higher water concentration whereas the U-, 3- and 7-membered

lactones hydrolyze more rapidly. IV. EXPEREffllTAI

Preparation and Purification of Materials

1,2-Dimethyoxyethane (Ansul Chemical Co., n^^l.3798, b.p. 8k-83°;

lit. (6k) n^^ 1.3797, b.p. 8k.7-8k.8°) was shaken with concentrated

hydrochloric acid, salted out with calcium chloride, rapidly dried with anhydrous magnesium sulfate and dried further by storing over

sodium hydroxide pellets for at least 2 days. Finally the 1,2-diraethoxy-

ethane was refluxed over calcium hydride or sodium for at least 10

hours and distilled. If not used immediately the solvent was stored

(6k) iî. Paloma and I. Honkanen, Ber., JO, 2199 (1937).

under nitrogen in a sealed bottle. The solvent to be used in the

kinetic runs (1,2-dimethoxyethane-water, 50:30 by volume at 25°) was stored in a glass-stoppered volumetric flask at 20° (constant

temperature room).

I. 3-Hydroxypropanoic Acid Lactone ( ^ -propiolactone)

3-Hydroxypropanoic acid lactone (B. F. Goodrich Chemical Co.) was rectified throu^ a glass-helix packed column and a center cut, b.p. 53.5° (11 mm.), n^® l.kl26, sap. equiv. calc'd. 72.0, sap. equiv. found 71.9 (65)j lit. (66) b.p, 150° (750 ram.), n^^ l.kl31, was used for kinetic studies.

6k 65

(65) All saponification equivalents were determined by potentio- metric back-titration of excess base.

(66) T. Gresham, J. Jansen, F. Shaver, and J. Gregory, J. Am. Chem. Soc., 70, 998 (I9h8).

II. 3~Hydro:çy-2-methylpropanoic Acid Lactone («X -methyl-/) - propiolactone)

This conpound was synthesized essentially as described by

Johansson (6?).

(67) H. Johansson, Chem. Zentr., II, ^ 558 (I916).

a) 3-Iodo-2-methylpropanoic acid. (68).

^ (68) This method is an adaptation of that of H. Stone and H. Shechter, J. Org. Chem., l5, U91 (1950) for synthesis of alkyl iodides from olefins or alcohols.

2-Methylpropanoic acid (methacrylic acid) (131 g., 1.50 moles), b.p.

70.2 - 71*2° (15 mm.), potassium iodide (750 g., 1|.50 moles) and 95^ phosphoric acid (obtained by adding the required amount of phosphoric anhydride to 85% phosphoric acid) were heated at 90-100° (1; hr.).

To the cooled solution were added ether (1000 ml.) and water (700 ml.).

The aqueous layer was separated and extracted with ether (3 x 200 ml.).

The combined ether solutions were washed with 10% sodium thiosulfate solution until colorless. After having been dried with anhydrous magnesium sulfate, the ether solution was evaporatdd and the residue 66

distilled to yield 3-iodo-2-methylpropanoic acid (269.7 g., 1.26

moles, 8k% yield), b.p. 109° (3 ram.), m.p. 37-38°; lit. (69) m.p. 39°.

(69) J. Glattfield and J. Schneider, J. Am. Chem. Soc., 60 , 1|17 (1936).

b) 3-H.ydroyy-2-raethylpropanoic acid lactone. 3-Iodo-2-

methyipropanoic acid (133.2 g., 0.623 moles) was dissolved in

sufficient sodium hydroxide solution(approximately 10^) to affect

conplete conversion to its salt. This solution was added (2 hr.)

to a mixture of silver nitrate (106 g., 0.635 moles) in water (150

ml.) at 0-5°' After washing the silver iodide precipitate with water, the combined aqueous solutions were extracted with ether

(3 X 75 ml.). The ether was removed under vacuum and the residue

distilled to yield 3-hydroxy-2-methylpropanoic acid lactone (27.0 g.,

50.5^ yield), b.p. 30-37.5° (1-3 mm.), 73° (28 mm.), 1.1x139,

infrared carbonyl band ^ 5.50^, sap. equiv. calc’d. 86.09, sap. equiv.

found 86.2; lit. (67) b.p. U9-50° (10 mm.).

m . 3-Sydroxybutanoic Acid Lactone (/0 -butyrolactone). (70).

(70) The method is a modification of T. Gresham, U. S. Pat. 2,356,459 (1945).

To a solution of boron trifluoride (3.7 g.) in ether (75 ml.) were added simultaneously acetaldehyde (33.0 g., 0.75 moles) in ether

(50 ml.) and ketene (71) at the rate of 0.76 moles/hr. at 10-15°. 67

(71) J. Williams and C. Hurd, J. Org. Chem,, ^ 122 (191^0),

After one hour dicyclohexylaraine (2^.0 g. ) was added to neutralize the boron trifluoride (72). The ether was removed under vacuum and the residue distilled to yield 3-hydroxy-3-methylpropanoic acid lac­ tone (38.3 g., 59.5^ yield), b.p. 30-37.5° (1-3 mm.). Fractionation through a glass-helix packed column yielded a kinetic sangle, b.p. 20 73° (28 mm.), ng l.iil28, infrared carbonyl band«6.50 p., sap. equiv. calc'd. 86.1, sap. equiv. found 87.0; lit. (73) b.p. 86-87° (50 mm.) njj 1.1|062.

(72) Although sodium hydroxide has been reported to have been used to neutralize the boron trifluoride (70) polymerization occurred in every attenpt. The use of dicyclohexylaraine was suggested by M. R. Frederick of B. F. Goodrich Chemical Co. in a private communication concerning the work of W. L. Beeares of B. F. Goodrich Chemical Co. with ketene and butyraldéhyde,

(73) F. Young and J. Fitzpatrick, U. S. Pat. 2,$60,71ii (1952).

. IV. 3-Hydroxy-3-methylbutanoic Acid Lactone (jS-isovalero- lactone)

3-Hydro%y-3-methylbutanoic acid lactone was synthesized from ketene and acetone in yield according to the method of Gresham

(70). Fractionation through a glass-helix packed column yielded a kinetic saitple of 3-hydr oxy-3-methylbut ano ic acid lactone, b.p. 20 70-71° (20 mm.), n^ 1.1^20, infrared carbonyl band/-* 3.50 p., sap. equiv. calc'd. 100.0, sap. equiv. found 98.0, lit. (7l|) b.p. 5it-55°, 20 , , nj) l.itl26 . 68

(7U) J. Caldwell, U. S. Pat. 2,1^^0,117 (I9k9).

7. 3-»Evdroyy-2,2-dimethylpropanoic Acid Lactone (e< ^ -diraethyl-

/3-propiolactone).

Triphenylphosphite (118.0 g., 0.38 moles) and methyl iodide

(5U g., 0.38 moles) were heated at 100° (10 hr.). 3-Hydroxy-2,2-

dimethylpropanoic acid (75) (U5*0 g., 0.38 moles) was added and the

heating continued (approximately 10 hr.). The mixture was cooled,

diluted with ether (100 ml.) and washed with saturated aqueous

potassium bicarbonate until evolution of carbon dioxide ceased.

The aqueous mixture was extracted with ether (3 x 100 ml.) and dilute

hydrochloric acid added to neutralize excess bicarbonate. This

solution was added rapidly to a mixture of silver nitrate (65.0 g.,

0.382 moles) in water (200 ml.). The precipitate of silver iodide was filtered and the filtrate extracted with ether (3 x 100 ml.).

After having been dried, the ether was evaporated to yield 3-hydroxy-2,

2-dimethylpropanoic acid lactone (3.0 g., 8.0$ based on 3-hydroxy-2,

2-dimethylpropanoic acid), b.p. Uh-U5° (10 mm.), infrared carbonyl

band ^5.50 /i, sap. equiv. calc’d. 100, sap. equiv. found 99.8.

(75) 3-Hydroxy-2,2-dimethylpropanoic acid was obtained by permanganate oxidation of neopentyl glycol as described by L. Wessely, Monatsch. Chem., 66 (1901).

A larger sançle of this lactone, generously supplied by Dr. H. M. Hill

of Tennessee Eastman Chemical Co., Kingsport, Term., had after dis­

tillation the following physical properties: b.p. 51*0-51.5° (12 mm.). 69 20 ng l.liOai;, infrared spectra identical to previous sample^ sap. equiv. calc’d. 100.1, sap. equiv. found 100.50. This material was used primarily for the kinetic investigations.

VI. Ij-Eydroxybutanoic Acid Lactone ( f -butyrolactone).

i;-Hydroxyhutanoic acid lactone (General Aniline and Film Corp.) was fractionated through a glass-helix packed column and a center cut, 20 b.p. 98° (22 mm.), n^ l.h3hls infrared carbonyl b a n d 5.70 >i, sap. 25 equiv. calc'd. 86.09, sap. equiv. found 87.0; lit. (76) njj 1.^318, b.p. 20l|°, was used in the kinetic runs.

(76) 0. McKinley and J. Copes, J. Am. Chem. Soc., 72, 5331 (1950).

VII. it-Hydroxy-2-methylbutanoic Acid Lactone, (ft-methyl-^ - butyrolactone).

This lactone was prepared in 1 5 . overall yield from diethyl methylmalonate and ethylene oxide according to Bryusova et. al. (77).

Rectification through a glass helix packed column yielded a kinetic 20 fraction, b.p. 85.1-85.5° (1^ mm.), n^ l.i;319, infrared carbonyl band about 5.70 p, sap. equiv. calc'd. 100.1, sap. equiv.ibund 101.0; 2C lit. ( ) b.p. °, l.i- . 78 197 b 320

(77) L. Bryusova, E. Simanovskaya and A. Ul’yanova, Sintezy Dustreslyidi Veshchestv, Sbomik Statei 1939, 165; Khim, Referat. Zhur., i£, 115 (I9it0), C.A., 3781; (19i;2).

(78) C. Marvel and H. Brace, J. Am. Chem. Soo., 70, 1775 (19l;8). — 70

VIII. It-gydroxypentanoic Acid Lactone ( y -valerolactone ).

il-Hydroxypentanoic acid lactone (Eastman Kodak Co., Rochester,

N.Y. ) was rectified throuÿi a glass-helix packed column and a center 20 cut, b.p. 88° (10 mm.), ng 1.1^318, sap. equiv. calc'd. 100.1, sap.

equiv. found 101.8; lit. (79) b.p. 80-83° ( H mm.), n^^ 1.1:307,

used in kinetic procedures.

(79) S. Glickman and A. Cope, J. Am. Chem. Soc., 1012 (19U5). — 1 ----

IX. i:-Hydroxy-l).-methylpentanoic Acid Lactone (y-isocapro-

lactone).

U-Hydro^gr-ii-methylpentanoic acid lactone was prepared essentially

as described by J. C. Westfahl (80) by hydrolysis of l:-methyl-lt-nitro-

pentanenitrile.

A mixture of hydrochloric acid (250 ml.) and li-methyl-li-nitro-

pentanenitrile (52.0 g., 0.365 moles) prepared according to Bruson

(81) from 2-nitropropane and propenenitrile (acrylonitrile) was

heated at 100-120° (29 hr.). After cooling the mixture,sufficient water was added to dissolve the ammonium chloride and the solution

extracted with ether (1; x 100 ml.). The ether extracts were washed with saturated aqueous potassium bicarbonate (100 ml.), dried with

anhydrous magnesium sulfate and evaporated. Distillation of the

residue gave ii-hydroxy-li-methylpentanoic acid lactone (l6.i| O.lijl;

moles, 39% yield), b.p. 92-94°' (15 mm.). Fractionation through a Vigreaux column yielded a kinetic fraction, b.p. 92.0-92.5° (15 mm.),

1 ,4315, infrared carbonyl band-m. 5*70^, sap. equiv. calc'd. 71

nil..11, sap. equiv. found 11^.0; lit. (80) b.p. 91-92° (l5 mm.),

l , h 3 1 $ .

(80) J. C. Westfahl, J. Am. Chem. Soc., 3U28 (1958).

(81) H. A. Bruson, Ü. S. Pat. 2,361,259 (19l|l|).

X. li-Bydroyy-2.2-dimethylbutanoic Acid Lactone ( -dimethyl-

V*-butyrolactone).

ll-Hydroxy-2>-2-dimethyibutanoic acid lactone was obtained in 52^

yield from condensation of ethyl isobutyrate and ethylene oxide using

sodium triphenylmethyl as base as described by Hudson and Hauser (82).

(82) B. Hudson, Jr. and C. Hauser, J. Am. Chem. Soc., 63, 3156 (19i|l). “ ■

Fractionation through a spinning band column yielded a kinetic 20 fraction, b.p. 194-195°, ng 1.4304, infrared carbonyl band about

5.75 fit sap. equiv. calc'd., 114.14, sap. equiv. found 113.9; lit.

(82) b.p. 195.5-197.5°.

XI. 4-H.vdroxy-3,3-dimethylbutanoic Acid lactone ( /3, (S-dimethyl-

y-valerolactone).

a) 4-Bromo-3.3-dimethylbutanenitrile. Neopentyl dibromide (440

g., 1.91 moles), sodium cyanide (95.5 g., 1.91 moles) and dimethyl

sulfoxide (1000 ml.) were heated on a steam bath for 66 hours. Water

and ice were then added until 2 layers separated. The aqueous layer

was then extracted with ether (4 x 300 ml.) and the combined organic

solutions were extracted with water (3 x 200 ml.). After having 72 been dried with anhydrous magnesium sulfate, the ether solution was evaporated and the residue fractionated throu^ a glass helix packed column to yield ij-bromo-3,3-dimethylbutanenitrile (76.0 g., 0.1|3 moles, 22.6# conversion), b.p. 91-95° (10 mm.), 79.2-79.3° (6 mm.), 20 nj) 1.1|7135 Anal., calc'd. for G^HigNBr: C, hO.k^i H, 5.68; N, 7.96;

Br, U5.1il; found; G, ip..19; H, 5.67; N, 8.09; Br, b5.10. Neopentyl dibromide, b.p. 60 -80° (10 ram.), lit. (83), b.p. 68° (9 mm.) was recovered in 35-50# yields and l,3-dicyano-2,2-dimethylpropane ob­ tained in conversions from 26-30# (identified by hydrolysis to

3,3-dimethylglutaric acid, m.p. 92-9ii°, lit. (8L) m.p. 98°).

(83) R. Shortridge, R. Craig, K. Greenlee, J. Derfer, and C, Boord, J. Am. Chem. Soc., 70, 9h6 (19Ü8).

(8ij.) J. Walker and J. Wood, J. Chem. Soc., 599 (1906).

b) h.-Hydroxy-3.3-dimetbylbutanoic acid lactone. U-Bromo-3,3- dimethylbutanenitrile (6l4,.2 g., 0.365 moles) and concentrated hydro­ chloric acid (500 ml.) were heated at 120° (55 hr.). The solution was cooled and extracted with ether (i; x 200 ml.). The ether solu­ tion was washed with saturated aqueous potassium bicarbonate (2 x

100 ml.), dried with anhydrous magnesium sulfate and evaporated to yield lt-hydro%y-3,3-dimethylbutanoic acid lactone (20 g., 0.175 moles, i|8# yield). Distillation yielded I6.8 g. (ip.# yield) of the lactone, b.p. 83-81;° (11 mm.). After 3 recrystallizations from

Skellysolve F (b.p. 35-55°), the properties of the lactone were: m.p. 58-59°j infrared carbonyl band-^5.70 sap. equiv. calc'd. 73

sap. equiv. found 113.30j lit. (85) b.p. 79.3° (10 ram.),

ra.p. 57.5*.

(85) F. Pattison and B. Saunders, J. Chem. Soc., 2?it5 (19b9).

XII. 5-Hydroîiypentanoic Acid Lactone (

5-Hydroxypentanoic acid lactone was prepared by a modification

of known procedures (86, 87, 15) by oxidation of cyclopentanone with

peroxytrifluoroacetic acid.

(86) W. F. Sager and A. Duckworth, J. Am.Chem. Soc., 77, 188 (1955). —

(8?) W. D. Emmons and G. R. Lucas, J. Am. Chem.Soc., 77, 2287 (1955). —

A solution of peroxytrifluoroacetic acid was prepared by addi­

tion (5 rain.) of trifluoroacetic anhydride (76.2 ml., 0.5b moles) to a

suspension of 90% hydrogen peroxide (12.6 ml., 0.b5 moles) in methylene

chloride (120 ml.) at 0°. This solution was added dropwise (75 rain.)

to a refluxing mixture of cyclopentanone (35 g., 0.35 moles) and

disodium hydrogen phosphate (300 g.) in methylene chloride (300 ml.)

in a one liter, 3-necked, round bottom flask equipped with constant pressure dropping funnel, stirrer, and Dry-Ice condenser. After the mixture had been refluxed for 5 hours, excess peracid was destroyed

upon addition of sodium carbonate (20 g.), and sufficient water

(approximately 500 ml.) was added to dissolve the solids. The aqueous layer was separated and extracted with methylene chloride 7k

(3 X 100 ml.). After having been dried with anhydrous magnesium

sulfate, the methylene chloride solutions were evaporated and the

residue distilled through a Vigreaux column to give 5-hydroxypentanoic

acid lactone (23>h g., 0.23b moles, 66% yield), b.p. 6?-7b° (2 mm.).

Redistillation through a Vigreaux column gave a kinetic sangjle, b.p. 20 69-69.5° (2 mm.), ng l.b569, infrared carbonyl band 5 . 8 0 sap.

equiv. calc'd. 100.1, sap. equiv. found 100.0; lit. (88), b.p. 88^ 2C (b ram.), nE^ l.b568.

(88) R. Linstead and H. Rydon, J. Chem. Soc., 580 (1933).

Since it was found that this lactone slowly polymerized even when stored at -20°, it was distilled and diluted with tiie kinetic

solvent just prior to use.

XIII. 5-Hydroxy-2-methylpentanoic Acid Lactone (pC -methyl-eT -

valerolactone).

a) 5-Iodo-2-methylpentanoic acid. 2-raethyl-5-phenox^entanoic

acid was prepared from diethyl methylmalonate and l-bromo-3-

phenoxypropane according to the method of Carter (89). A mixture of

(89) A. S. Carter, J. Am. Chem. Soc., 196? (1928).

2-methyl-5-phenoxypentanoic acid (130 g., 0.6b moles), potassium iodide

(b50 g., 2.b2 moles) and 95^ phosphoric acid (by addition of phosphoric

anhydride to 85^ phosphoric acid) (360 g., 3.69 moles) was heated at

120 -125° (7 hrs.) (70). Water (300 ml.) and ether (500 ml.) were

added and the aqueous layer extracted with ether (3 x 150 ml.). The 75 combined ether solutions were washed with 10% aqueous sodium thio- sulfate until colorless, and then with 10% sodium carbonate solution

(h X 100 ml.). The carbonate solution was poured slowly into dilute hydrochloric acid; a red oil separated which was dissolved in ether.

After having been dried, the ether solution was evaporated to yield

^iodo-2-methylpentanoic acid ( H 8 g., 0,h97 moles, 78% yield).

This material was used in the next step without further purification.

b) $-Hydroxy-2-methylpentanoic acid lactone. 5-Iodo-2-methyl- pentanoic acid (ii2.5 g., 0.176 moles) was dissolved in sufficient

10^ potassium carbonate solution to effect conçlete conversion to its salt. This solution was rapidly added to a mixture of silver nitrate

(30 g., 0.177 moles) in water (100 ml.). After having been filtered, the solution was extracted with ether (3 x 150 ml.). The residue ob­ tained after evaporating the dried (anhydrous magnesium sulfate) ether solution was distilled to yield 5-hydroxy-2-methylpentanoic acid lactone (7.5 0.0658 moles, 35/o yield), b.p. 106.5-107.5°

(li; mm.). Fractionation of the material from 2 such experiments gave a kinetic sample, b.p. 90-91° (5 ram.), n^^ 1.^558, infrared carbonyl band 5*80 sap. equiv. calc’d. llU.Hi, sap. equiv. found nit.5; lit. (90) b.p. n6-%17° (16 mm.).

(90) E. Hollo, Ber., 895 (1928). 76

XI7. ^-Hydroxyhexanoic Acid Lactone ( J”-caprolactone ).

5-Hydroxyhexanoic acid lactone was prepared in 77^ yield by oxidation of 2-methylcyclopentanone (91) with peroxytrifluoroacetic acid by the general method described previously for 5-hydroxypentanoic acid lactone (p,73).

(91) This material was prepared by alkylation of 2-carbethoxy- cyclopentanone according to M. Comubert and C. Barrel, Bull. soc. chim. France, i;0 , ijTj 301 (1930).

The infrared spectrum, when coirç)ared with that of 5”hydroxy-2- methylpentanoic acid lactone (the other possible isomer), showed none of the characteristic bands of the latter confound. Fractiona­ tion through a glass-helix column yielded a kinetic fraction, b.p. 20 103° (10 mm.) m.p. 19°, ng 1.^338, infrared carbonyl band about

3.80jif sap. equiv. calc'd. llii.li^, sap. equiv. found 113.30; lit.

(92) b.p. 1130 (20 mm.), m.p. 17-19°, n^O 1.4L31 (93).

(92) R. Linstead and H. Rydon, J. Chem. Soc., 2000 (193b). 20 (93) M. Hudlicky, Chem. Listy, 380 (1952), reports n^ l.b589<

XV. 5-Hydroxy-3,3-dimethylpentanoic Acid Lactone (^ dimethyl- S -valerolactone).

a) 3,3-Dimethylglutaric acid. 3,3-dimethylglutaric acid was prepared in 60 ^ yield by oxidation of 2,2-dimethyl-l,3-cyclohexanedione

(dimedone) according to the method of Smith and McLeod (9b) with the exception that sodium hypobromite was substituted for sodium hypochlorite. 77

(9U) W. Smith and G. McLeod, Org. S y n . , ^ , i;0 (19$1).

3,3-Dlmethylglutaric anhydride. 3,3-Dimethylglutaric acid

(ijl»5 g.J 0.259 moles) and acetyl chloride (60 ml.) were heated on a

steam bath (90 min.). Skellysolve F (b.p. 35-55°) (15 ml.) was

added and the mixture cooled to 0°. The solid was filtered and dried

to yield 3^3-dimethylglutaric anhydride (25.0 g., O.I76 moles, 68%

yield), m.p. 111-118°; lit. (95) m.p. 125°.

(95) J. Cason, G. Sumrell, and R. Mitchell, J. Org. Chem., 15, 850 (1950).

c) 5-Hydroxy-3,3-dimethylpentanoic acid lactone. 5-%dro%y-3,

3-dimethylpentanoic acid lactone was prepared in $3% yield by reduc­

tion of 3f 3-dimethylglutaric anhydride with sodium and ethanol, as

described by Rydon (96).

(96) H. Rydon, J. Chem. Soc., 39k (1936).

Two fractionations through a Vigreaux column gave a kinetic

fraction, b.p. 122.5-123° (20 mm.), m.p. 35.8-35.9°, infrared car­ bonyl band/.x 5.8O sap. equiv. calc'd. 128.17, sap. equiv. found

127.50; lit. (96) b.p. 118-120° (20 ram.), m.p. 29°.

XVI. 5-Hydroxy-2,2-dimethylpentanoic Acid Lactone. ( ,<,»< -

dimethyl- ^ -valerolactone).

a) 2,2-Dimethylglutaric anhydride was prepared from 2,2-

dime thylglutaric acid, according to the procedure for 3,3-dimethyl­

glutaric anhydride (p.%^). This acid was prepared by nitric acid 78 oxidation of 2 ,3,3-triniethyl-l-cyclopentenecarbo2ylic acid (obtained by treatment of isocamphoric anhydride with aluminum chloride) by known methods (97).

(97) B. Shive, J. Horeczy and H. Lochte, J. Am. Chem. Soc., 27hh (19U0).

b) ^-Hydroxy-2,2-dimethylpentanoic acid lactone. ^Hydroxy-2,

2-dimethylpentanoic acid lactone was prepared in 39% yield by reduc­ tion of 2,2-diraethylglutaric anhydride with sodium and ethanol by the method of Rydon for reducing 3,3-dimethylglutaric anhydride (96).

Rectification in a spinning band column yielded a kinetic sanç)le, 20 b.p. 91.0-91.8° (10 mm.), n^ l.lik93, infrared carbonyl band^ 5.80 sap. equiv. calc'd. 128.17, sap. equiv. found 126 .0, lit. (98), b.p. 220°, 105° (13 mm.).

(98) M. Blanc, Bull. soc. chim., France 3 , 33, 897 (1905).

XVII. 5-Hydroxy-5-methylhexanoic Acid lactone. (

cT -valerolactone).

A sample of 5-hydroxy-5-metbylhexenoic acid lactone was supplied by H.K. Hall, Jr. of E. I. DuPont de Nemours & Co. Inc., Wilmington,

Del. Distillation through a Vigreaux column gave a kinetic sample, 20 b.p. 91.2-91.5° (5 ram.), n^ l.W:96, infrared carbonyl band 5.80 u, sap. equiv. calc'd. 128.17, sap. equiv. found 127.30, lit. (99) b.p, or] 90° (3 mm.), n^ l.Ui97.

(99) R. Linstead and H. Rydon, J. Chem. Soc., 580 (1933). 79

XVIII. 6-IWro%rhexanoic Acid Lactone ( é. -caprolactone),

A sanple of this lactone was obtained from Union Carbide Plas­ tics Co., Bound Brook, N.Y. Rectification through a glass helix packed column yielded a center cut for kinetic studies, b.p. 108° 20 (10 mm.), njj l.i|6l9, infrared carbonyl band'- 5.80 ^u, sap. equiv. calc'd. Hi;.Hi, sap. equiv. found Hii.30j lit. (lOO) b.p. 98° 25 — (9 mm.), ng l.ii605.

(100) M. Stoll and A. Rouve, Helv. Chim. Acta., 1^, 108? (1935)'

XIX. 6-Hydroxyheptanoic Acid Lactone. (6 -methyl-6 - caprolactone).

This lactone was obtained in %% yield by oxidation of 2-raethyl- cyclohexanone (obtained from Dr. K. Greenlee of The Ohio State Univer­ sity Research Foundation; American Petroleum Institute Project 55) with pero^qytrifluoroacetic acid according to the procedure described previously (p.73). Fractionation through a glass-helix packed column 20 yielded a kinetic sample, b.p. 100-101.5° (6 mm.), n^ 1.55&9, infra­ red carbonyl band w 5.80 )i, sap. equiv. calc'd. 120.17, sap. equiv. found 127.00; lit. (101) b.p. 95° (5 mm.), n^° 1.5558.

(101) P. S. Starcher and B. Phillips, J. Am. Chem. Soc., 80, 5079 (1958). 80C

Determination of Kinetic Constants

Equipment

Constant teraperature baths» The bath usedafc 0° was an 11 liter wide-mouth Dewar vessel, insulated and enclosed by a wooden framework, and filled with crushed ice and distilled water. A constant tempera­ ture of -0.05°+.01° was easily maintained by occasional manual stirring.

The other two baths were large commercial constant tençerature baths maintained at l6.1°+o.l° and 25.0h°+O.Ol° (thermometer cali- 0 brated in 0.01 ) respectively. For one series of esgieriments the higher teitperature bath was maintained at 2$.07°+0.01°.

Conductometrlc equipment. The apparatus used was identical to that used by Flanagan (102).

(102) P. W. K. Flanagan, Ph. D. Dissertation, The Ohio State University (195?)•

A 2000 cps signal from an oscillator (Jackson Electrical Equip­ ment Co. Model 652) was led to a 1:1 isolation transformer and then to a modified Jones-Joseph (Leeds and Northrup) bridge (range: 0-60,000 ohms). The signal from the bridge was led through another trans­ former to a preangjlifier (a voltage amplifier). Shielded leads led the signal from the amplifier to the Y-input of an oscilloscope

(Dumont Model 208-B) used as a null point indicator. Disappearance of the 2000 cps trace on the oscilloscope indicated the bridge was in balance. 81

Conductivity cells» The cells used were those developed by

Flanagan (102) utilizing vertical, non-platinized electrodes.

Hypodermic syringes. The syringes used (Becton-Dickenson. &

Co., Yale Luer-Lok type) had maximum capacities of 2, and 10 milliliters. They were calibrated from the weight of distilled water (25°) discharged. The 2 and 5 milliliter syringes were found

to be correct as marked. After calibration the syringes were found

to deliver the indicated volumes within +0.02 ml.

Kinetic Techniques

Solvents and standard solutions. The solvent used in all experi­ ments was a mixture of 1,2-dimethoxyethane and water (1:1 by volume

at 25°). It was found that a mixture of 1,2-dimethoxyethane and water (63.i4-:36.5^ by weight) used in this laboratory previously for

lactone hydrolysis (15) was not applicable to conductometric methods.

A number of runs with ii-hydroxybutanoic acid lactone using this sol­ vent showed an apparent concentration effect which may be caused by

ion-pair formation as a result of the low dielectric constant of the

solvent. This effect disappeared when the solvent composition was 1:1 by volume. The 1,2-dimethoxyethane was purified as previously

described (p.6)^). Although a previous investigator in this labora­

tory (15) boiled the solvent prior to use in kinetic runs, this was found to be unnecessary, since kinetic constants determined with

freshly prepared solvent agreed closely with those determined in

solvent exposed many times to the air over a period up to one month. 82

Carbonate-free sodium hydroxide solution was prepared by-

dissolving sodium hydroxide pellets in an equal weight of distilled water. After standing several hours the mixture was filtered -through

a sintered glass funnel and stored in a polyethlene bottle. Standard

solutions in 1,2-dimethoxyethane-water were prepared by diluting the

concentrated sodium hydroxide solution with dimethoxyethane and water

(25°) and titrating (20°) an aliquot potentiometrically with standard

hydrochloric acid. These standard solutions were stored in poly-

e-fchylene bot-tles equipped with polyethylene delivery tubes and air

inlet tubes containing Ascarite-filled drying tubes. These storage

bottles allowed the standard solutions to be easily transferred to

the syringes without contamination by carbonate. No positive carbonate

test (with approximately 1 N barium chloride solution) could be

detected with these solutions during the period of -fcheir use.

Standard solutions of 5-^ 6- and 7-membered lactones were pre­ pared by diluting a weighed sançle of the lactone with the 1,2-

dimethoxyethane-water solution (1:1 by volume at 25°) at 20°.

S-bandard solutions of li-membered lactones were prepared in pure 1,2-

dimethoxyethane since -these lactones undergo uncatalyzed water hydroly­

sis. 5-Hydroxy-2,2-dimethylpentanoic acid lactone was also treated

in -this manner because of its low solubility in the kinetic solvent.

In all cases the normalities of the solutiorfs of lactones were made

to equal that of the solution of standard base. These lactone:

solutions were sufficiently stable to give reproducible rate cons-bants

during the period of -their use (2 days to 1 month. 83 Preparation and execution of a kinetic run. Upon completion of a kinetic run the cells were washed several times with distilled water. "While not in use the cells were kept filled with distilled water.

In preparation for a run, the cells were rinsed twice with absolute ethanol and dried by a slow stream of filtered air. The desired volume of solvent and required amount of standard base were injected into the cell at 20° with the calibrated syringes. With the 4-membered lactones and 5-hydroxy-2,2-dimethylpentanoic acid lactone a known volume of distilled water (20°) was also injected at this point to allow for the fact that the solvent for the standard solutions for such lactones was l,2-dimethyo3^ethane rather than 1,2- dimethoxyethane-water (1:1 by volume at 25°). The cells were imme­ diately stoppered and suspended in a constant temperature bath.

Hypodermic syringes were filled with slightly more than the required volume of standard lactone solution at 20° and also suspended in the constant temperature bath after having been capped with a small rubber policeman. The cells and syringes were allowed to equilibrate in the baths for at least one hour. It was found that the resistance of the solutions remained unchanged after this time.

Before starting a run, the resistance was set at a reading approximately 10^ higher than that of the equilibrated cell. The total resistance range obtained during a reaction was divided into convenient intervals. These valves were then consecutively set on the bridge during the run and the time of balance noted. It was Qk also necessary to balance capacitance during a run. In general

iiiany more points could be obtained than were required.

The run was initiated by remoTing the syringe from the bath,

removing the rubber cap and adjusting to the required volume (10 sec.),

The solution was rapidly injected into the cell and the time noted.

The glass stopper of the cell was replaced and the solution shaken

(U-5 sec.). In all cases the volumes of lactone solution, base and

solvent were corrected for change in volume from 20° to reaction

temperature. This correction amounted to +0.02 ml., -0.02 ml. and

-0.18 ml. per 10 ml. solvent at 25°, lii° or 16°, and 0° respectively.

The hydrolyses were generally followed to 50-75% completion.

R qo values were taken after 7-8 half-lives and checked for

constancy.

Calculations and Kinetic Methods

The method of calculation of rate constants was that used by

Mar on and LaMer (103).

(103) S. Maron and 7. LaHer, J. Am. Chem. Soc., 60, 2588 (1938).

Derivation is as follows:

For a reaction of the type:

A + B — ) C + D

the rate of reaction is given by:

& = k23b (1) where a, b and c are equal to concentrations of A, B, and C respective­

ly. 85

If a = b, then a = b = Bq - c, in which the subscript o indicates initial concentration. Equation 1 then becomes

Integration of Equation 2 gives:

1 = %2t + K . (3) au-c

If t = 0, K = J thus . . «n

Rearrangement of Equation 4 gives:

^2 = TT. apt 'ao-c (5)

1 c/Bq ^2 = ^ (TZcTs;)

If the conductivities (>.) of the ionic species are additive and vary linearly with concentration, and since the fraction of material reacted at time t is given by c/a^, then:

c ^0 ^ ' ' (7) -jrrj^ 0 ^ 0 0

^ 0 “ is the fraction of the total conductivity change which has ^ 0 - "^oo occurred at time t. 86

Experiments were run to check the assunçtion of linearity of concentration of sodium hydroxide solutions with their conductances.

Linearity was found to approximately 10“^ molar. It is apparent that additivity and "linearity" of conductances of both sodium hydroxide and a hydroxy carboxylate anion produced in hydrolysis hold at much higher concentration since no apparent deviation in rate constants was noted in kinetic experiments in which the concentrations were $ x 10"2 molar.

Since conductance is inversely proportional to resistance,

Equation 7 becomes;

^0 “ ^ ^00 ,^"^0 ^ c

00

Combining Equations 7 and 8 gives:

or:

a 0 i f 0

Thus a plot of t(Eoo-E) versus E gives a straight line with Y

intercept of I.

"Rod , . "Rqo I = ^ , and k2 = rS; (11) 87

Advantages of this method are: (l) Rq need not be determined, this obviates approximation methods for determining a quantity which cannot be directly measured; (2) k2 does not depend on the absolute value of the conductance or the magnitude of the conductance change; cell constants need not be determined therefore. Also, additional conductance from extraneous ions will not affect the calculation.

A disadvantage of the method is its sensitivity to R ^ . Errors in

R 00 are approximately doubled in the rate constant. Errors due to hydrolysis of salts of the hydroxy acids are insignificant (less than 0.1^) because of their low degree of hydrolysis.

In general, plots of t(Roo-R) versus R gave good straight lines for the first 6o% of reaction. A few runs gave straight lines to 30% reaction. There appeared to be no correlation between the rate constant and the length of the straight line. In the latter stages of a kinetic experiment the plotted points curved below the line; the curvature is believed to result from the fact that the reactants were not present in exactly equal concentrations. Errors due to very small inequalities in initial concentration are progressively magni­ fied as the saponification proceeds to completion.

Because of the possibility of contamination by carbonate from a side reaction of 3-hydroxy-3-methylbutanoic acid lactone (see p. 85 for discussion), the measured R^j value was checked as follows: A plot of t versus R (from first 1 0 % of reaction) was extrapolated to t(j to determine Rq» This value of Rq was compared with that calculated from: 88

% / 2 Ro = 9 _ p, ,_/p.. (12) ° 2 - R1/2/R00

in which the value of R q is dependent on the measured R qj and R^/Q

®l/2 determined from values of R versus t where t = t^yg as given by:

H / 2 = 3 ^ (13)

Using this method, an error of 10$ in Rqo will lead to at least a 5$ error in Rq. Since in all cases the extrapolated and calculated values of Rq checked within ±1$, it was concluded that the R^j values measured in saponification of 3-hydroxy-3-methylbutanoic acid lactone were good to at least + 2%. A similar analysis for a number of other lactones indicated errors of about the same magnitude.

Additional errors may arise from teiiperature fluctuations of the constant temperature baths during reaction. The maximum variance was +0.1°. Since conductivity changes about 2% for each degree, the maximum error in conductance from this source will be ±0.2$, which will lead to an error in rate constants of about ±1$,

A special problem exists with 3-hydroxy-3-methylbutanoic acid lactone (/3-isovalerolactone) in that it undergoes a unimolecular decarboxylation reaction concurrent with hydrolysis (see discussion of this effect in section entitled "Reactions of beta-Isovalero- lactone in Water," p./S'), In order to measure only the bimolecular basic hydrolysis rate it was necessary to devise conditions whereby the decarboxylation reaction was essentially "swanped out" by the 89 normal basic hydrolysis reaction. Since the rate of the decarboxy­ lation reaction is dependent only on lactone concentration, whereas the hydrolysis depends on both lactone and base concentrations, it was possible to increase the rate of the hydrolysis relative to decarboxylation merely by increasing the concentration of both react­ ants j the decarboxylation increases proportionally to the first power of the lactone concentration and the hydrolysis proportionally to the square of lactone concentration (since the lactone and base concen­ trations were kept equal in all kinetic runs). In reactions at

0° it was found that at concentrations of approximately 0.02 M plots

of t (RgQ -E) vs R were noticeably curved, whereas at concentrations from

O.Oii to 0.06 M straight lines resulted (rate constants varied less than 2%i Table , in Appendix) (lOij). A more pronounced trend was noted at lh° and 25°j the concentration ranges which gave straight lines were 0.015 M to 0.030 M and 0.029 M to O.Obb M respectively.

(lOb) Although at concentrations below 0.02 M, the lines were not completely straight, the best straight line through the initial points gave rate constants within a few percent of those obtained at concentrations greater than 0.02 M.

A complicating result was noted in this system which was partic­ ularly evident at 25°. At certain concentrations below those stated,

it was found that plots of t(Roo-R) vs. R gave straight lines, but reproducible rate constants could not be obtained when the concentra­

tions were varied. The rates decreased with increasing concentration

(see Table VUE). This effect may be a result peculiar to the method

(conductoraet ic) for following the rates. At any particular time the 90 total conductance is proportional to the individual conductances for all species present. Therefore if carbonate is present as a result of decarboxylation the conductivity will be proportional to the con­ centrations of base, hydroxycarboxyiate ion and carbonate ion. (The conductance of the lactone will be very small). Since the carbonate ion will conduct more highly than the hydroxy-carboxylate ion because of its larger charge per unit mass, it may be compensating for the lower concentration of hydroxy-carb03cylate ion (as a result of the side reaction consuming lactone to produce carbonate). Since carbon dioxide will consume twice the amount of hydroxide ion as the lactone, it will have to be produced at only half the rate of hydrolysis to consume base at the same rate as does the hydrolysis reaction. The result of these compensating factors may well be an apparent single second order hydrolysis reaction when in reality mixed second order hydrolysis and first order decarboxylation are occurring. Such processes would also explain the observed increase in rate with decreasing concentrations, evident below optimum concentrations.

R qo values for the hydrolyses were checked as described on p. f y . Rate constants for the hydrolyses at the three temperatures determined as described above, gave a straight line for the activation energy plot (see Fig. 12). 91

Table ¥111

Rates of Hydrolysis of beta-Isovalerolactone as a Function of Concentration

Gone, (m./l., base=lactone) k2 (l./m. X min.)

0.006373 18.1

0.007089 17.U

0.007737 16.8

O.OIL60 9.1U

0.02158 8.82

0.02920 8.16

0.01380 7.32

Activation Parameters

The activation parameters were calculated from the following equation: (105)

(105) A. A. Frost and R. G. Pearson, "Kinetics and Mechanism," John Wiley and Sons, New York, 1953, p. 96.

f (Ik) 92 where:

k2 = rate constant (l./mole min.)

k = Boltzman constant (erg./deg.)?

T = Kelvin tençerature (°K)

h = Planck constant (erg. min.)

= entropy of activation (cal./mole deg.)

a H* = enthalpy of activation (cal./mole)

R = gas constant (cal./deg. mole)

Plots of log ^ versus ~ gave straight lines with slope equal to - H /2.303 R (See Appendix). Since the enthalpy values are only as accurate as the rate constants (usually within ±3%) the errors will be within +0.3 kcal./mole. Entropies were calculated from:

A S * ='' + U .576 log — - 55*36 (15)

(This equation is derived from Equation li| by insertion of above units and rearrangement.) Rate constants were determined at three temperatures. Entropies were calculated for each temperature using

Equation 15, and an average value taken. Only differences in entropy of about 2 e.u. will be significant since the error may be as high as + 1 e.u. APPENDIX

93 3- Hydroxy -2- Methyl propanoic Acid Lactone

Run: 84 Cone. 0.009471 m/l. 10,000 Temp. -0.05® = 19.7 l./m. x min.

0,000 cr 50% reaction ' epoo cr.

4,000

2,0 0 0 -

WOO 1600 1800 2000 2200 R FIGURE 6 0 0 - 3~Hydroxy-3“ Methylbuta noic Acid Lactone Run: 266 Cone. 0.04380 rn./l. Temp. 25.0® kg = 7.32 l./m x min. 500-

400- cr 50% reaction I 8 cr 300-

200

100 150 170 190 210 230

FIGURE 2 ré

1500 4 - Hydroxypentanoic Acid Lactone Run: 132 Cone. 0.01411 m./l. Temp. 25.0® - 22.8 l./m. x min.

1000-

X I 50% reaction 8 X

500

lOOL 310 400 450350 500 R

FIGURE ^ 7

4 - Hydroxy -2,2“ Dimethylbutoncic Acid Lactone 1000 Run: 268 Cone. 0.02790 m./l. Temp. 25.0® kg =771 l./m. x min.

50% reaction cr I a?

100

240 260 280 300 320

FIGURE 4 9i

19,000 5- Hydroxy he xa noic Acid Lactone

17,000_ Run: 126 Cone. 0.0008572 m./l. Temp. 16.1® k2=43l l./m. x min.

15,000 50% reaction

11,000

spoo

7,000 iqpoo 10,500 R

FIGURE 5 9^

5- Hydroxy -2,2-Dimethylpentanoic Acid Lactone ,000 Run: 222 Cone. 0.001905m/l J Temp. 14.0® ^2 ~ 172 l./m. xmiri^

9000 50% reaction

7000 0: 8 0: 5000

3000

1000 -

5000 5500 6000 6500 7000

FIGURE 6 ^06

6 - Hydroxyheptanoic Acid Lactone 2^00 .Run = 215 Cone 0.02980 m/l. Temp. -0.05® kg = 5.20 l./m. x mirv 50% reaction

2000

(T I Q? 1500

1000

400 380 420 460 500 540 R FIGURE t o i 0 .6 5 0 - 25.0 3 - Hydroxypropanoic Acid Lactone

0.450- I AH 1.0 kcGl./mcle

0.250-

0050-

-005 0.0035 0.0037

FIGURE 8 25.0 3-Hyd rosy “2-Methylpropanoic Acid Lactone AH* = 10.8 kcol. /mole 0.450-1

16.1

0250-1

0.050-1

-0.05 0.850-2 0.0033 0.0035 0.0037

FIGURE 9 25.0

3 - Hydroxybutanoic 0 .000-1 Acid Lactone AH* = 12.2 kcol /mole

0.800-2

O'

0.400-2

-0.05

0.0033 0.0035 0.0037

T FIGURE 10 /ôf 0.750-2 25.0 3-Hydroxy-2,2-Dimethylpropanoic Acid Lactone AH^ = 110 kcol./mole

0.550-2

14.0

0.350-2

0.150-2

0.0035 00037 FIGURE I 0400-2 25.0 /OS

3 -Hydroxy-3“ Methylbutanoic Acid Lactone

.8 kcol. /moleAH

0.200-2

140

0.000-2

0.800-3

-0.05 0.600-3 0.0033 0.0035 00037 FIGURE 12 0.350- 25.0 4-Hydroxybutanoic Acid Lactone AH" = 11.0 kcol./mole

0.150-

0950-2

0.750-2

0550-2 0.00350.0033 0.0037 J_ T FIGURE 13 /i>7 0.050- 25.0 4^Hydroxy -2- Methylbutanoic Acid Lactone

10.8 kcal./mole 0.850-2

0650-2

0450-2

-0.05 0.250- 2 0.0033 0.0035 0.0037 J_ T FIGURE 14 f o g

0.900-2 25.0 4- Hydroxypentanoic Acid Lactone

AH II.I kcol./mol

0.700-2 16.1®

0.500-2

o*

0.300-2

-0.05

0.100-2 0.0033 0.0035 0.0037 FIGURE 15 /Of 0.450-2 25.0 4- Hydroxy -2,2- Dimethylbuta noic Acid Lactone AH* = 11.0 kcal./mole

0.250-2

14.0

0050-2

0.850-3

-0.05® 0.650-3 0.0033 0.0037 FIGURE 16 7 /0 25.0® 0.400- 2 4 - Hydroxy - 3,3 “Dimethylbutanoic Acid Lactone 11.7kcol./mole

0.200-2

14.0

0.000-2

O'

0.800-3

-0.05

0.0033 0.0035 0.0037

T FIGURE 17 t a 0.450-2

25.0

4 -Hydroxy -4-Methylpentanoic Acid Lactone AH 10.4 kcol./mole 0.250-2

0.050-2

0B50-3

-0.05 0.650-31 __ 0.0033 0.0035 0.0037 FIGURE 18 70C" 25.0® 5 “Hydroxypentanoic Acid Lactone AH^ = 8.2 kcol./mol

.500-

300

r0.05' 1001___ 0.0033 0.0035 0 0037 J_ T FIGURE 19 i/3

0.350 5-Hydroxy -2-Methylpentanoic Acid Lactone

25.0® =7.3 kcol./mole

0.150

I- o*

0.950-1

-005 0.750-1 0.0033 0.0035 0.0037 FIGURE 20 //f

0.400 25.0 5- Hydroxy hexanoic Acid Lactone

= 8.0 kcol./tnole

0.200

0.000

0.0035 0.0037 J_ T FIGURE 21 / / r

0.000 25.0 5-Hydroxy- 2,2 -Dimethylpentanoic Acid Lactone =73 kcol. / mole

0600-1 14.0®

0.600-

-005

0.400-1 0.0033 0 0 0 3 5 0.0037

T FIGURE 22 0.800-2 tfl

25.0 5- Hydroxy-3,3 -Dimethylpentanoic Acid Lactone AH*= 10.3 kcol./mole 0.600-2

0.400-2

o* o

0200-2

-0.05

0.000-2 00033 0 .0 0 3 5 0.0037

FIGURE 23 0.250-2

2 5 0

5“ Hydroxy-5-Methylhexonoic Acid Lactone AH^ = 10.9 kcol./mole 0.050-2

14.0'

0.850-3

O'

0.650-3-

-0 05

0.450-3 0.0033 0.0035 0.0037

FIGURE 24 / / r 0.450- 6 - Hydroxyhexanoic Acid Lactone kcol/mole 250

0.250-

0.050- 14.0

O'

0B50-2

r0.05

0.0035 0.0037

T FIGURE 25 //f 0.050-1 r

6-Hydroxyheptanoic Acid Lactone

AH* = 8.7 kcol./mole 25.0 0.850-2

0.650-2 14.0

0450-2

-005 0.250-2 000 33 00035 0.0037 FIGURE 26 IZO

Table IX

3-EydroxypropaDoic Acid Laotone

Run = { j = 6 9 Temp. -0.05 Cell A Cone. 0.007680

t (min.) R t (Roo-R)

0.57 1200 819 1.12 1250 1552 1.72 1300 2298 2.38 1350 3061 3.08 1400 3807 4.68 1500 5316 6.62 1600 6858 8.93 1700 8358 11.78 1800 9848 15.12 1900 11,128 00 2636 —— -

I = -16,964 -2636 = 20.2 c -16,964 X 0 .007680

Run i f l O Temp. -0.05 Cell B Cone. 0.008380

t (min.) R t (Roo-E)

0.47 1600 911 1.23 1700 2261 2.10 1800 3650 3.08 1900 5045 4.18 2000 6429 5.42 2100 7794 6.85 2200 9165 8.48 2300 10,498 10.38 2400 11,812 12.65 2500 13,131 CO 3538 — —

I = -21,327 kp = . -3538 = 19.8 c -21,327 X 0 .00838 12.1 Table x

5-Eydroxypropanoio Acid Lactone

Run #71 Temp. -0.05 Cell A Cone. 0.009947

t (min.) R t (Rq o -R)

0.93 1000 1001 1.53 1050 1570 2.18 1100 2128 2.90 1150 2685 3.72 1200 3259 4.63 1250 3824 5.68 1300 4408 6.87 1350 4988 8.20 1400 5543 9.67 1450 6053 11.57 1500 6664 00 2076 ----

I = -10,333 k« = -2076 = -10,333 X 0.009947

Run #63 Temp, 16.1 Cell A Cone. 0.005370

t (min.) R t (R(X) -R)

0.32 1000 304 0.65 1050 585 1.02 1100 867 1.43 1150 1144 1.92 1200 1440 2.43 1250 1701 3.07 1300 1996 3.78 1350 2268 4.60 1400 2530 00 1950

I = -5371 V*' = -1950 . = gy g -5371 X 0.005370 TableX I

g-Eydroxypropatioio Acid Lactone

Run = j r 6 7 Temp. 16.1 Cell A Cone. 0.005370

t (min.) R t(Roo-R)

0.33 1000 315 0.67 1050 605 1.05 1100 896 1.47 1150 1180 1.95 1200 1468 2.50 1250 1758 3.15 1300 2057 3.87 1350 2334 4.72 1400 2610 00 1953

I = -5482 kg - _54g2 % 0.005370 ~

Run j j = 6 8 Temp. 16.1 Cell B Cone. 0.006802

t (min.) R t(RoQ-R)

0.40 1250 450 0.92 1350 944 1.13 1400 1103 1.43 1450 1324 1.75 1500 1533 2.12 1550 1751 2.52 1600 1956 2.97 1650 2156 3.47 1700 2346 4.03 1750 2523 00 2376 --- 02376 I = -509 7 kg =.— cnof? n nnfiQAO = 68.5 Table XU

3-Hydroxypropanoic Acid Lactone

Run fS5 Temp. 25.0 Cell A Cono. 0.004580

t(mn.) R t (Rq o -R)

0.40 900 254 0.72 950 420 1.12 1000 598 1.58 1050 765 2.15 1100 935 2.83 1150 1085 3.72 1200 1241 4.88 1250 1385 6,47 1300 1513 8.80 1350 1620 00 1534

1= -2317 -1534 = iio kg = -2817 X 0.004580

Run t t 5 9 Temp. 25,0 Cell A Cone. 0.003600

t(mim.) R t (Rq o -R)

0.18 1100 166 0.45 1150 392 0.75 1200 616 1.10 1250 849 1.50 1300 1081 1.95 1350 1310 2.47 1400 1532 3.08 1450 1760 3.80 1500 1980 4.65 1550 2190 5.72 1600 2410 CO 2021

I = -4768 -2021 = nfl ^2 = -4768 X 0.003600 lableXUI . I 3-ïïydroxy-2-methylpropanoic Acid Lactone

Rug Temp. -0.05 Cell D Cono. 0.01040

t(min.) R t(RoQ-R)

0.48 900 534 1.00 950 1062 1.62 1000 1639 2.27 1050 2184 3.02 1100 2754 3.95 1150 3405 4.80 1200 3898 5.85 1250 4458 7.03 1300 5005 9.92 1400 6071 00 2012 — — — —

I 9816 kg = _ Q Q i Q ^ 0.01040 "

Run j j = 8 4 : Temp. -0.05 Cell F Cono. 0.009470

! (rain.) R t (R«)

0.30 1350 508 0.67 1400 1101 1.02 1450 1626 1.45 1500 2239 1.92 1550 2868 2.32 1600 3350 2.93 1650 3803 3.50 1700 4704 6.23 1900 6599 9.98 2100 9421 00 3044 -3044 I = -16,356 kg = _i0^356 % 0.009470 " Table X/v ^2 5 "

3-Eydro:cy-2-methylpropanoic Acid Laotoae

Run #86 Temp. -0.05 Cell D Cono. 0.01016

t (min.) R t(Roo-H)

0.35 950 417 0.80 1000 912 1.33 1050 1450 1.90 1100 1976 2.57 1150 2544 3.30 1200 3119 5.05 1300 4242 7.22 1400 5343 9.97 1500 6381 00 2142

I = -10,556 -2142 =9n.n ^2 = -10,556 X 0.01016

Run #79 Temp. 16.1 Cell A Cono. 0.007560

t (min.) R 't(Roo"^)

0.63 800 411 1.03 850 620 1.53 900 845 2.10 950 1054 2.80 1000 1266 3.65 1050 1467 4.72 ^ 1100 1661 00 1452 — — —— — -1452 _ I = -3023 ^2 = -3023 X 0.007560 Table X V 126 3-Hydroxy-2-Methylpropanoie Acid Laotoae

Rua #80 Temp. 16.1 Cell B Conc. 0.008260

t (min.) R t(Roo-R)

0.52 1050 463 1.10 1150 870 1.43 1200 1060 1.83 1250 1265 2.28 1300 1461 2.78 1350 1643 3.37 1400 1823 4.07 1450 1998 4.68 1500 2152 00 1941 —-— .. , I = -3740 ^2 = -3740 X 0.008260

Run #81 Temp. 16.1 Cell F Conc. 0.008890

t (min.) R t(RcxTR)

0.52 900 398 0.67 925 496 0.92 950 658 1.00 975 690 1.58 1050 972 2.07 1100 1170 2.65 1150 1365 3.30 1200 1535 4.13 1250 1714 00 1665 — — — ... -1665 _ I = -3085 kg = -3085 X 0.008890 Table Xv I IZ7 5-Eydroxy-2-methylpropanoic Acid Lactone

Run #77 Temp. 25.0 Cell D Conc. 0.008230

t (min.) R t (Rq o -R)

0.30 550 131 0.45 575 186 0.62 600 241 0.82 625 298 1.02 650 345 1.27 675 396 1.57 700 452 1.93 725 508 2.32 750 552 00 988

I = -1053 -988 5 na. ^2 = -1053 X 0.008230

Run #82 Temp. 25.0 Cell B Conc. 0.005940

t (min.) R t(Roo-H)

0.40 1125 338 0.60 1175 478 0.83 1225 610 1.10 1275 754 1.42 1325 902 1.78 1375 1041 2.20 1425 1177 2.72 1475 1319 3.00 1500 1380 CO 1971

I = -2945 -1971 _ ^2 = -2945 X 0.005940 Table X V U

g-Hydroxybutanoio Acid Lactone

Run 7^145 Temp. -0.05 Cell A Conc. 0.01940

t (min.) R t(R(D -R)

0.48 480 296 1.20 500 716 1.98 520 1142 2.85 540 1587 3.82 560 2051 4.88 580 2523 6.07 600 3017 7.38 620 3520 8.85 640 4044 00 1097 -1097 I = -11,766 ^2 = - 11,766 X 0.1940 "

Run #146 Temp.-0.05 Cell B Conc. 0.02030

t (min.) R t(Roo -R)

0.42 680 368 0.90 700 771 1.40 720 1172 1.97 740 1609 2.55 760 2032 3.17 780 2463 3.85 800 2914 4.57 820 3368 5.33 840 3822 6.17 860 4300 7.05 880 4773 00 1557 4773 -1557 I = -15,184 ^2 = : 15,184 X 0.02030 " Table x v/l/

3-Hydroxybutanoio Aoid Laotoae

Run #147 {Eemp. -0.05 Cell G Conc. 0.02110

t (min.) R t(RodB)

0.42 450 248 1.13 470 645 1,88 490 1036 2.73 510 1450 3.70 530 1891 4.75 550 2332 5.93 570 2792 7.25 590 3270 7.97 600 3515 00 1041 —-—

I = -10, 547 -1041 =4,70 '=2 ' -10. 547x0.02110

Run #143 Temp. 16.1 Cell D Conc. 0.006290

t (min.) R

0.77 850 642 1.17 870 952 1.60 890 1270 2.05 910 1587 2.57 930 1938 3.08 950 2260 3.67 970 2620 4.27 990 2963 4.92 1010 3316 5.60 1030 3662 6.37 1050 4039 00 1648

I = -13, 718 -1684 . . ^2 -13, 718 X 0.006290 Table X l X 130 3~Hydroxybutanoic Acid Laotoae

Run ^142 Ten^. 16.1 Cell A Cono. 0,005122

t (min.) R t (Rq q -R)

0.67 1025 687 2.10 1100 1995 2.63 1120 2446 3.02 1140 2748 3.52 1160 3133 4.05 1180 3524 4.63 1200 3936 5.23 1220 4341 5.88 1240 4763 6.58 1260 5198 00 2050 ■ v w m a a

I = -19,901 ko = “2050______20.1 -19,901 X 0.005122

Run =ifl39 Temp. 25.0 Cell A Cone. 0.003107

t (min.) E t (Rq q -R)

0.62 1300 609 1.35 1350 1260 2.23 1400 1969 3.25 1450 2707 4.47 1500 3500 5.02 1520 3830 5.58 1540 4146 6.22 1560 4497 7.57 1600 5170 00 2283

I = -21,102 k« =_____ “2283______= 35. -21,102 X 0.003107 Table XX 131 3-Sydrozybutanoio Aoid Laetone

Rua 140 Temp. 25.0 Cell B Conc. 0.04077

t (min.) R t (Rgo-R)

0.12 1450 156 0.72 1500 899 1.20 1550 1438 1.75 1600 2009 2.35 1650 2580 3.07 1700 3217 3.83 1750 3288 4.70 1800 4456 5.70 1850 5119 6.80 1900 5766 00 2748

I = -18,473 k« = — --- = 2.85 -18,473 X 0.004077

Run ü5^246 Temp. -0.05 Cell F Conc. 0.02980

t (min.) R t (Ro o -R)

0.65 470.5 432 1.12 480.5 880 3.95 530.5 2388 4.93 550.5 2882 7.60 590.5 4138 10.65 630.5 5373 16.17 690.5 7188 00 1135 — —

I = -14,100 ko = , -1135 c j>^7n -14,100 X 0.2980 TableXXJ 133. 3-Eydrozy-2,2-dimethylpropanoic Acid Lactone

Run #245 Temp» -0.05 Cell E Conc. 0.02550

t (min.) R t (Ro o '

0.83 600.5 687 1.73 620.5 1397 2.67 640.5 2103 3.68 660.5 2824 4.78 680.5 3573 5.95 700.5 4329 9.28 750.5 6287 15.08 820.5 9161 00 1427

I = -21,320 ko = -1427 = 2.85 -21,320 X 0.02350

Run #246 Temp. -0.05 Cell F Conc. 0.02980

t (min.) R t (Roo-R)

0.65 470.5 432 1.12 480.5 880 3.95 530.5 2388 4.93 550.5 2882 7.60 590.5 4138 10.65 630.5 5373 16.17 690.5 7188 00 1135 -1135 I = -14,100 ko = = 2.70 2 “ -14,100 X 0.2980 Table XX11 133 5-Eydroxy-2,2-dimethylpropanoic Acid Lactone

Run ü^64 Temp. -0.05 Cell 0 Conc. 0.02980

t (min.) R t (Ro o -R)

1.58 340 713 2.52 350 1023 3.12 360 1345 4.83 380 1985 6.72 400 2628 8.82 420 3272 11.15 440 3914 12.42 450 4235 00 791

I = -10,190 k" = = 2.61 -10,190 X 0.02980

Run ^260 Temp. 14.0 Cell A Conc. 0.02940

t (min.) R t (Rqo "R)

0.52 210 123 1.00 220 226 1.55 230 335 2.13 240 438 2.77 250 543 4.28 270 753 6.10 290 952 8.40 310 1142 00 446 — -

I = -2080 = -446 = 7.30 -2080 X 0,.02940 Table XXIII 134. 5-Hydroxy-2,2-dimethylpropatioio Acid Laotoae

Run #261 Temp. 14.0 Cell C Conc. 0.01469

t (min.) R t (Roo-R)

0.58 400 263 1.57 420 680 2.63 440 1086 3.82 460 1501 5.13 480 1913 6.53 500 2305 8.12 520 ' 2704 9.92 540 3105 12.00 560 3516 00 853 ---- -853 I = -7890 Tr^ = — r? m ^ -7890 X 0.01469 ---

Run #263 Temp. 14.0 Cell F Conc. 0.02160

t (min.) R t (R^-R)

0.30 380 136 1.08 400 467 1.83 420 754 2.65 440 1039 4.52 480 1591 5.62 500 1866 8.28 540 2418 00 832

I = -5140 k. = -832 = 7.Rn 2 -5140 X 0.02160 Tabl®X^|\/

5-Hydroxy-2,2-dimethylpropatioic Acid Lactone

Run. #258 Temp. 25.0 Cell F Cono. 0.02920

t (min.) R t (Roo-R)

1.07 250 201 1.38 260 246 1.73 270 291 2.58 290 382 3.67 310 470 5.13 330 554 6.08 340 596 œ 438 — — -

I = -910 V - -438 _ T „ r- 2 -910 X 0.02920

Run #259 Tenç. 25.0 Cell E Cono, 0.01460

t (min.) R t (Roo-R)

0.25 400 103 0.73 420 285 1.27 440 471 1.87 460 656 2.50 480 828 3.23 500 1006 5.55 550 1449 00 811

I = -3560 V = -811 - 2 -3560 X 0.01460 TableX X V |

5~Hydroxy-2,2-dimethylpropaaoio Aoid Laotone

Rua #262 Temp. 25.0 Cell E Conc. 0.02155

t (mia.) R t (Roo-R)

0.27 280 74.5 0.78 300 200 1.07 310 263 1.37 320 323 1.68 330 380 2.05 340 443 2.43 350 501 3. 33 370 619 5.08 400 792

c o 556

I = -1596 -556 _ -1596 X 0.02155 Table XXVI ‘^7 S-Hydroxy-5»methylbutanoic Aoid Lactone

Run #251 Temp. -0.05 Cell E Cono. 0.06160

t (min.) R t (Rç^-R)

1.98 270 628 3.17 280 973 4.47 290 1328 5.83 300 1673 7.28 310 2017 8.83 320 2358 10.53 330 2706 12.30 340 3038 14.23 350 3373 00 587

^2 “ _8680 X 0.06160

Run #225 Temp. -0.05 Cell C Cono. 0.04900

t (min.) R t (R^q -R)

1.55 300 563 2.80 310 988 4.15 320 1423 5.60 330 1865 7.17 340 2316 8.82 350 2761 13.47 375 3879 17.72 395 4749 00 663 ——

I * -12,810 kg » .12^810 X 0.04900 “ Table XX VI i I 3 S 3"Hydro3cy-5-iC6tlylbutanoio Acid laotoae

Run ^ 6 Temp. -0.05 Cell E Cono. 0.02030

t (min.) R t (Rgo-R)

.92 680 828 2.68 700 2358 3.70 710 3219 4.77 720 4102 5.92 730 5030 7.15 740 5989 8.42 750 6989 11.83 775 9583 14.02 790 11076 00 1580 —

I = -70,600 = -1680 g 1,10 -70,600 z 0.02030

Run #257 Temp. 14.0 Cell A Conc. 0.02160

t (min.) R t (Eo o -R)

1.13 290 559 2.17 300 629 5.30 310 924 4.50 320 1215 8.60 350 2064 13.76 380 2888 00 590 —

I = -8170 -590 - -ii ^2 -8170 X 0.02160 Table X X v n I ^ g ^

3-Eydroxy-3-Biethylbutanoic Acid Lactone

Run #254 Temp. 14.0 Cell A Conc. 0.01469

t (min.) R t (Roo-E)

0.42 400 180 1.42 410 595 2.43 420 994 3.57 430 1424 4.68 440 1821 5.85 450 2217 7.08 460 2613 8.43 470 3027 14.40 510 4594 CO 829 —

I * -16,260 « -829 g 3.47 kg -16,260 z 0.01469

Run #253 Temp. 14.0 Cell F Conc. 0.02940

t (min.) R t (Rco-E)

0.90 310 293 2.42 330 738 4.10 360 1169 6.07 370 1609 8.33 390 2041 10.83 410 2437 00 635

I » -6490 . “6.35 - 3 31 k2 -6490 z 0.02940 * Table XX / X (4-0 ^3-Hydro3cy-5-methylbutaaoio Aoid Lactone

Rua 4 ^ 5 5 Temp, 25,0 Cell E Coao, 0,02920

t (min») E t (Rq q -R)

0,72 230 147 1,18 240 229 1.72 250 316 2,30 260 400 2,97 270 487 3.68 280 567 4.45 290 641 5.32 300 713 CD 434 ——"

■454 I « -1819 kg « -1819 X 0,02920 “

Run #266 Temp, 25,0 Cell F Conc, 0,04580

t (min.) R t (Rq^-E)

0,70 160 100 1.23 170 164 1.88 180 231 2.63 190 297 3,50 200 361 4.58 210 426 5,82 220 483 7,42 230 542 00 305

"2 ' .M6 Table xxx , . , I 4-1 S-Hydroxy-S-inethylbntanoio Acid Laotoae

Run #265 Temp. 25«0 Cell E Cono. 0.03595

(min.) R t (Rco'

0.87 190 144 1.42 200 220 2.03 210 294 2.72 220 367 3.65 250 441 4.45 240 509 5.48 250 575 6.75 260 639 00 555

^2 “ -1265 X 0.03595 “ Table VXK/ 141 4-Hydroxybutaaoic Acid Laotoae___

Rua ^23 Temp. -0.05 Cell A Coao. 0.01040

t (mia.) R ■t i ^ o o

1.23 925 1430 1.83 950 2080 2.98 1000 3240 4.25 1050 4410 5.58 1100 5500 7.17 1150 6730 8.85 1200 7850 10.73 1250 9000 12.83 1300 10,110 17.83 1400 12,240 00 2085

-2085 I = -19,861 k, = _ -19,861 X 0.0104

Rua i f 2 5 lemp. -O.Oü Cell A Coao. 0.008900

t (mia.) R t (Rœ

1.15 1050 1583 2.25 1100 2980 3.37 1150 4300 4.62 1200 5670 7.37 1300 8300 8.97 1350 9660 10.70 1400 11,000 14,67 1500 13,600 19,55 1600 16,190 25.55 1700 18,600 00 2427

I = -26,946 k, = :2j27______= lo.l ^ -26,946 % 0.008900 TableXXXII 14-3 4-Hydroxybutan.oic Acid Lactone

Run 7^26 Temp. -0.05 Cell B Conc. 0.01330

t (min.) R t (Rq c -^)

0.58 1050 810 1.11 1100 1498 2.88 1200 3600 3.77 1250 4530 4.72 1300 5430 6.88 1400 7230 8.13 1450 8130 9.50 1500 9020 12.67 1600 10,750 16.65 1700 12,500 00 2450

I = -18,295 k. = -2450 = 10.1 -18,295 X 0 .01330

Run ^37 Temp. 16.1 Cell A Conc. 0.007270

t (min.) R t (Roo-R)

0.87 750 613 1.65 800 1068 2.50 850 1510 3.55 900 1970 4.82 950 2437 6.33 1000 2880 8.13 1050 3290 10.48 1100 3720 13.63 1150 4160 00 1455

I = -6358 k_ = -1455 ._ = 31.4 -6358 X 0.007270 TableXXXIII 144- 4-Eydro3cybut&aoic Acid Lactone

Run ^39 Temp. 16.1 Cell A Cone. 0.004370

t (min.) R t (Ro o -PO

0.32 1125 346 1.43 1200 1440 2.27 1250 2172 3.20 1300 2900 4.22 1350 3620 5.38 1400 4340 8.08 1500 5720 11.72 1600 7130 16.50 1700 8360 00 2207 — — — -

I = -6071 k g = , ,.....-2207 , -31.4 -6071 X 0.004370

Run = j f 4 0 Temp. 16.1 Cell B Cone. 0.005820

t (min.) R t (Rqo **R)

0.25 1300 331 0.72 1350 917 1.18 1400 1445 2.27 1500 2555 3.50 1600 3590 4.27 1650 4160 5.05 1700 4660 6.90 1800 5690 9.25 1900 6710 12.22 2000 7650 CO 2625 — —

I = -13,950 ko = -2625 = 32.4 Ci -13,950 X 0.005820 Table X% X I ^ (4i- 4-Eydroxybutanoic Acid Lactone

Run Temp» 25,0 Cell A Cone. 0.004310

t (min.) R t (Roo-R)

0.20 900 163 0.75 950 575 1.35 1000 965 2.05 1050 1362 2.83 1100 1740 3.77 1150 2130 4.87 1200 2510 6.15 1250 2860 7.78 1300 3226 9.83 1350 3585 00 1750

I = -6669 kg = -6669 X 0.004310mn/sin " 59.6

Run ^34 Temp. 25.0 Cell B Cone. 0.005800

t (min.) R t (^00

0.42 1050 391 0.75 1100 660 1.17 1150 970 1.63 1200 1270 2.13 1250 1555 2,72 1300 ... 1850 4.18 1400 ' 2430 6.23 1500 2990 9.28 1600 3530 00 1980

I = -5742 k« = -1980 = RQ.s C -5742 X 0.005800 Table XXXV 1 4 6 é-Hydroxybutanoic Acid Lactone

Run ^36 Temp» 25.0 Cell B Cone. 0.007200

t (min.) R t (^00 -R)

0.28 825 218 0.45 850 338 0.83 900 583 1.27 950 830 1.78 1000 1071 2.33 1050 1316 3.08 1100 1549 3.95 1150 1788 5.03 1200 2023 6.38 1250 2245 00 1250

I = -3800 k2 = = RR,R -3800 X 0.007200

Run #38 Temp. 25.0 Cell B Gone. 0.005800

t (min.) R t (Roo-PO

0.37 1050 357 0.70 1100 640 1.08 1150 933 1.50 1200 1220 2.00 1250 1528 2.55 1300 1820 3.93 1400 2410 5.78 1500 2965 8.45 1600 3500 00 2014

I = -5822 -2014 = SQ,R ^2 = -5822 X 0.005800 Table X'Xxv/ I 1+7 4~Eydroxy-2-methylbutanoic Aoid Lactone

Run ^27 Temp. -0.05 Cell A Cone. 0.01480

t (min.) R t (R^o-R)

1.50 650 1320 3.50 700 2905 5.77 750 4500 8.37 800 6110 11.35 850 7710 14.80 900 9320 18.77 950 . 10,880 23.67 1000 12,530 29.40 1050 14,110 00 1530 -1530 I = -19,480 ko = _ = 5.30 -19,480 X 0.01480

Run #28 Temp. -0,05 Cell 3 Cone. 0.01330

t (min.) R t (&00

1.47 1050 2120 4.20 1150 5625 7.38 1250 9150 11.17 1350 12,720 15.72 1450 16,360 21.20 1550 19,900 24.38 1600 21,700 27.98 1650 23,500 32.03 1700 25,300 00 2490 — — — "

I - -35,860 kg = _gg ggo X 0.01330 ^ ^'21 Table >^XXVH 148 4-Hydroxy-2-methylbutanoic Acid Lactone

Run #30 Temp» -0.05 Cell B Oonct 0.01330

t (min.) R t (Roo

1.38 1050 1950 4.15 1150 5450 7.42 1250 3000 11.23 1350 12,500 15.83 1450 16,020 21.48 1550 19,610 28.42 1650 23,100 32.58 1700 24,800 -2462 I = -35,141 ko = 6 -55,141 I 0.01330 = 5.28

Run #51 Temp. 16.1 Cell A Cone. 0.007505

t (min.) R t (Rq o '

0.30 700 247 1.45 750 1120 2.67 800 1930 4.27 850 2875 6.05 900 3765 8.07 950 4630 10.50 1000 5490 13.50 1050 6380 21.48 1150 8040 CD 1523 -1523 I = -12,172 ko = -12,172 X 0.007505 = 16.7 Table XXXVIII

4-Eydro:cy-2-methylbutatioic Acid Lactone

Run t^ 2 Temp. 16«1 Cell B Cone. 0.009961

t (min.) R t (Roo

0.95 850 866 1.83 900 1578 2.80 950 2275 3.90 1000 2975 5.15 1050 3665 6.62 1100 4380 8.32 1150 5100 12.53 1250 6420 18.88 1350 7780 00 1762 “ ™ -#

I - -11,030 k2 .11^030 z 0.009961 “

Run #55 Temp. 16.1 Cell A Cono. 0.008576

t (min.) R t (R«)

1.65 650 870 3.28 700 1565 5.27 750 2250 7.72 800 2910 10.88 850 3560 14.88 900 4130 CD 1177

^ " "8312 ^2 ■ -8312 X 0.008576 " I®*® Table X I X I S O 4-Hydro3cy-2-inethylbutaaoio Aoid Lactone

Run #49 Temp. 25.0 Cell A Cone. 0.008554

t (min.)______R______t (R^^-R)

0.38 500 196 1.32 550 614 2.50 600 1038 3.97 650 1450 5.92 700 1865 8.57 750 2275 10.68 780 2510 00 1015 ———*

Run # 5 0 Temp. 25.0 Cell B Cone. 0.01069

t (min.) R t (Rq^-R)

0.35 600 202 0.97 650 545 1.72 700 881 2.62 750 1210 3.70 800 1525 5.13 850 1855 6.95 900 2170 8.88 940 2415 00 1213 —— *

I = -3633 k_ = ---- ilii?----- = 31.3 2 -3633 X 0.01069 Table XL ,

4-Hydroxy-2-methylbutanoic Acid Lactone

Run #54 Temp. 25.0 Cell B Cone. 0.009630

t (min.) R t (Roo-S)

0.37 650 248 1.00 700 621 1.75 750 1000 2.62 800 1365 3.72 850 1752 5.05 900 2125 6.73 950 2500 8.92 1000 2865 10.00 1020 3010 00 1321 — — -1321 _ _ I = -4630 ^2 -4630 X 0.009630 l a b l e X W I SU. 4-Hydroxypentanoic Aoid Lactone

Run 1^156 Temp. -0.05 Cell A Cone. 0.01998

t (min.) R ■t (P-oo '

0.42 480 297 1.43 500 981 4.23 550 2690 6.12 580 3709 8.90 620 5037 11,25 650 6030 13.83 680 6998 16.72 710 7959 00 1186 — — — —

: ' ' -15,9ÎéTo.01998 '

Run tt157 Temp. -0.05 Cell B Cone. 0.02094

t (min.) R t (Poo'

0.83 700 821 1.52 720 1473 2.70 750 2535 3.77 780 3427 4.58 800 4072 5.42 820 4710 6.77 850 5680 9.18 900 7243 10.80 930 7867 11.93 950 8816 00 1689

I - -21,560 k2 = .21^560 % 0.02094 " TableXL/1 15*3 4-Hydroxypentanoio Acid Lactone

Run #138 Temp. -0.05 Cell C Cono. 0.02114

t (min.) R t (Rqo‘

0*37 450 245 1.37 470 880 2.95 500 1805 4.68 530 2723 5.95 550 3344 7.28 570 3946 9.52 600 4874 11.95 630 5760 13.75 650 6353 00 1112

Run fflSS Temp. 16.1 Cell A Cone. 0.01893

t (min.) R t (Rq q -R)

0.45 300 158 1.08 320 356 2.17 350 651 3*00 370 840 4.48 400 1120 5*70 420 1310 7.92 450 1584 9.83 470 1770 00 650

: = ' - 2 Æ i T b . 0 i 8 S 3 ' TableXL.»!/ I S ' ^ 4-üycLroxypeatanoio Acid Lactone

Run #124 Temp. 16.1 Cell B Cone. 0.01984

; (min.) R ■fc (^00'

0.97 450 453 1.42 470 634 2.17 500 905 2.73 520 1080 3.7- 550 1355 4.42 570 1530 5.70 600 1800 6.68 620 1980 CD 916 — “ —

: = ^2= -554^'fo.01984 =

Run ^135 Temp. 16.1 Cell C Gone. 0.02075

; (min.) R t (Rc o '

1.30 310 387 2.02 330 562 2.85 350 736 3.80 370 905 5.60 400 1163 7.10 420 1335 CO 608

I = -2328 kp = ZÊ2Ê______= 13.1 -2328 X 0.02075 Table XL (V

4-Eydro3iypenatDoic Acid Lactone

Rua #130 Temp. 25.0 Cell A Cone. 0.01004

t (min.) R t (Roo-R)

1.25 450 494 2.75 500 949 3.48 520 1131 4.73 550 1395 5. 73 570 1576 7.47 600 1830 10.57 640 2167 00 845

I = -3574 ko = - "845 “ 23 6 2 ■-3574 X 0.01004 ~

Run #131 Temp. 25.0 Cell B Cone. 0.01228

t (min.) R t (Roo-R)

0.13 500 72 0.92 550 462 1,88 600 850 3.07 650 1234 4.58 700 1612 6.57 750 2116 00 1052

I = -3850 -1052 - 22 3 ^2 " :-3850 X 0.01228 “ TableyLV ( S’6

4-Eydroxypetitanoic Acid Lactone

Run 7^=132 Temp. 25.0 Cell C Cone. 0.01411

t (min.) R t (Roo-R)

0.23 310 77 1.18 350 347 1.77 370 485 2.82 400 688 4.12 430 882 5.22 450 1013 8.22 490 1266 00 644

I - -2000 kg = - -644 - oc Q ■2000 X 0.01411 [email protected] I g-y

4-Hydroyy~2,2-dimethyIbutaaoie Acid Lactone

Run ^#275 Temp* -0.06 Cell A Cone» 0.02720

t (min.) R t (Rq^-R)

0.63 350 282 2.17 360 948 3.80 370 1623 5.48 380 2285 7.30 390 2971 9.15 400 3633 11.05 410 4276 15.20 430 5578 00 797 ••

I . -23.000 fcj . .33 ,o (x )T o .02720 '

Run t^ 74 Temp. «0.05 Cell C Cone. 0.02850

t (min.) R t (Egg-R)

0.67 340 286 2.22 350 926 3.85 360 1567 5.55 370 2203 7.32 380 2833 9.20 390 3468 11.12 400 4081 00 767 • •

•767 I = -21,300 k2 = .21,300 x 0.02850 “ TablaXLVII ,^g

4-Hy

Run #275 Temp. -0.05 Cell D Cono. 0.02980

t (mln«) R t (Roo-R)

1.33 330 559 2.90 340 1189 4.55 350 1820 6.25 360 2438 8.06 370 3059 9.97 380 3689 10.90 390 4250 14.00 400 4900 00 750 —

I = -20,000 —750 — 1 '’fi ^2 -20,000 z 0.02980

Run #270 Temp. 14.0 Cell A Cono. 0,02680

t (min.) R t (Roo-R)

0.45 220 103 1.48 230 324 2.58 240 539 3.78 250 752 5.07 260 958 6.50 270 1164 8.08 280 1366 9.83 290 1563 00 449 —

-449 I = -4480 k2 -4480 X 0.02680 Table XLVI11 15:7 4-Hydroay»2,2~cLlmethylbutanoic Acid Lactone

Run = U = Z 7 1 Temp» 14.0 Cell C Cono. 0*02810

t (min.) R t (Rg^-R)

1.07 220 232 2.13 230 .414 4.63 250 866 5.88 260 1041 7.38 270 1232 9.05 280 1421 10.90 290 1602 00 437 —

—437 I « -4200 kg “ -4200 x 0.02810 “

Run #272 Temp. 14.0 Cell D Cone. 0.02940

t (nin.) R t (Rgg-R)

0.83 210 175 1.88 220 378 3.00 230 573 4.26 240 769 5.67 250 970 7.18 260 1156 8.83 270 1333 00 421 Table x L I X /60

4-Eydroxy-2,2-dimethyIbutanoic Acid lactone

Run #267 Temp. 25.0 Cell A Cono. 0.02665

t (ndn.) R t (Roo-R)

0.85 170 125 1.65 180 226 2.56 190 324 4.75 210 508 6.18 220 599 7.83 230 681 9.88 240 761 00 317

I = -1560 “ K 7 g* kg -1560 % 0.02665

Run #268 Temp. 25*0 Cell F Cono. 0.02790

t (min«) R t (Rgo-R)

0.72 230 145 1.27 240 243 1.85 250 335 2.50 260 428 3.23 270 520 5.97 300 782 8.45 320 938 00 431 —

I = -2005 c 1 1 - 7.71 %2 -2005 % 0.02790 Table L ^ ^ ^

4-Eydroxy-2,2-àimethylbutanoio Acld lactone

Run. f Z G 9 Temp. 25.0 Cell E Cono. 0.02920

t (min.) R t (Roo-R)

0.40 210 75 0.95 220 165 1.52 230 254 2.17 240 341 2.88 250 423 3.68 260 504 5.63 280 658 8.25 300 800 00 397

-397 I = -1712 *2 “ -1712 X 0.02920 “ Table Ll /42.

4-Eydroxy-5,5~dimethylbufaanoic Acid Lactone

Run f:165 Temp» -0.05 Cell A Cone. 0.02291

t (min.) R t (Roo-R)

1.78 450 1104 3.28 440 2001 4.83 450 2898 6.43 460 3794 8.10 470 4698 9.80 480 5586 11.57 490 6479 13.38 500 7359 23.48 550 11,740 00 1050 --- -1060 _ I = -38,000 ^2 =:-38,000 X 0.02291

Run ^166 Temp. -0.05 Cell C Cono. 0.02540

t (min.) R t (Roo-R)

0.35 390 206 1.82 400 1052 3.30 410 1874 4.82 420 2690 6.35 430 3480 9.62 450 5079 • 13.13 470 6670 00 978 -978 I = -31,630 kg = _31^630 x 0.02540 " Table i-M

4-Eydroxy-5,3"dimethylbutaaoio Acid Lactone

Run #167 Temp. -0.05 Cell D Cone. 0.02785

t (min.) R t (Hqo “^)

1.57 360 824 2.97 370 1530 4.52 380 2283 6.08 390 3010 7.77 400 3768 9.40 410 4465 11.18 420 5199 13.05 430 5938 00 885 -

I = -25,500 "BBS = 1.24 ^2 = -25,500 X 0.02785

Run #168 Temp. 14.0 Cell E Cone. 0.02255

t (min.) R t (Roo-R)

0.80 380 366 2.12 400 926 3.53 420 1472 5.70 440 2013 6.78 460 2556 8.68 480 3038 10.73 500 3541 12.93 520 4008 14.17 530 4251 00 837 — — “B37 _ g yg I = -9960 ko = 2 -9960 X 0.02255 TableU(H 1&4 4-Eydroxy»5,3-cLimethylbutanoic Acid Lactone

Run ^169 Temp. 14,0 Cell B Cone. 0.02060

t (min.) R t (Roo-R)

0.38 420 193 1.68 440 818 2.98 460 1392 4.42 480 1978 5.93 500 2523 7.63 520 3105 9.50 540 3677 11.55 568 4239 13.80 580 4789 00 927 -927 I = -11,890 ^2 = -11,890 X 0.02060 3'79

Run T f H O Temp. 14.0 Cell F Cone. 0.02380

t (min.) R t (Roo-R)

0.42 360 185 1.68 380 706 3.05 400 1220 4.55 420 1729 6.20 440 2232 8.02 460 2727 10.10 480 3232 12.40 500 3720 00 800 -800 I = -8880 = -8880 X 0,.02380 5.82 Table LIV

4-Hydroxy-5,5-dimethylbutanoie Acid Lactone

Run #162 Temp. 25.0 Cell B Conc. 0.01826

t (min.) R t ( ^ 0 0 "E)

0.45 360 171 1.30 380 467 2.22 400 753 3.25 420 1037 4.43 440 1325 5.75 460 1604 7.23 480 1873 9.02 500 2156 œ 739 ---

I = -4940 -739 _ OQ - -4940 X 0.01826

Run #163 Temp. 25.0 Cell E Conc. 0.01988

t (min.) R t (Roo-R)

0.72 320 238 2.65 360 769 3.82 380 1031 5.18 400 1295 6.77 420 1557 8.65 440 1817 10.92 460 2075 13.72 480 2332 œ 650

I - -3960 ko = -650 = a 2g 2 -3960 X 0.01988 Table L V

4-Eyd.rozy-3,3-dimethyIbutanoi c Aoid Lactone

Run #164 Temp. 25.0 Cell F Conc. 0.02121

t (min.) R t (Ro o '

0.73 310 229 1.65 330 485 2.63 350 721 3.80 370 965 5.13 390 1240 6.70 410 1434 8.58 430 1665 10.90 450 1897 CO 624

^ ^2 ■ -3555 X 0.02121 ” 8.25 Table LV I

4-Hydroxy-4‘^8'fcliylpetitanoic ,Acid Lactone

Run ^159 Temp. -0.05 Cell B Conc. 0.04236

t (min.) R t (Roo-R)

0.42 300 226 1.50 310 770 3.15 325 1570 4.28 335 2090 6.08 350 2880 7.97 365 3680 9.30 375 4160 11.33 390 4940 12.87 400 5450 15.18 415 6200 00 824 -- -

I = -15,670 -824 = 1 0 4 2 r 15,670 X 0.04236

Run a = 1 6 0 Temp. -0.05 Cell E Conc. 0.04465

t (min.) R t (Roo-R)

0.67 260 296 1.83 270 790 3.00 280 1263 4.28 290 1760 5.60 300 2240 9,87 330 3650 11.42 340 4140 13.05 350 4588 00 701 —-

I = -12,090 _ ‘701 . ^ 2 " ■-12,090 X 0.04465 Table UV/1 tig

4 -Hydro3cy~4 -methylp6 Qtanoic Acid Laotone

Run ^161 Temp. -0.05 Cell F Conc. 0«04611

t (min.) R t (Roo-E)

0.75 250 336 1 . 8 8 260 823 3.68 275 1510 5.57 290 2270 6 . 8 8 300 2730 10,50 325 3900 12.87 340 4590 14.58 350 5050 00 697 — -

I = -11,520 k, = . . _:.697 -11,520 X 0.04611

Run ^156 Temp. 16.1 Cell A Conc. 0.01420

t (min.) R t (Roo-R)

0.95 350 425 2.95 350 1260 5.08 370 2070 7.43 390 2875 • 10.07 410 3700 13.00 430 4510 13.78 435 4710 00 777

I = -12,870 k, = -777 2 -12,870 X 0.01420 Table LVili

4:“Eydroxy-4-inethylpentanoic Acid Lactone

Run t^157 Temp; 16.1 Cell C Cone. 0.01515

t (min. ) R t (Roo -R)

0.75 310 322 2 . 2 0 325 908 3.75 340 1490 6 . 0 0 360 2265 7.23 370 2660 1 0 . 8 8 ^ 400 3680 14.45 425 4530 00 738

I = -11,800 -738 ^ 2 = -11,800 z 0.01515

Run 1^158 Temp. 16.1 Cell D Cone. 0.01620

t (min.) R t (Roo-R)

0 . 6 8 290 286 1.63 300 670 2.62 310 1050 3.63 320 1418 4.72 330 1795 5.83 340 2160 7.05 350 2540 11.08 380 3660 14.18 400 4390 00 710 — —- —

I = -10,560 kg = = 4,15 -10,560 X 0.01620 Table L IX iqo

4-Eydroxy-4-methylpeatanoic Acid Lactone

Run j r l 5 Z Temp. 25,0 Cell B Conc. 0.01073

t (min.) R t (Roo-R)

0.78 520 456 1.83 540 1034 2.95 560 1610 4.15 580 2180 5.42 600 2740 6.82 620 3300 8.32 640 3865 9.93 660 4420 11.70 680 4975 CD 1105 -1105 I = -14,405 kg = -14,405 X 0.01073 ■

Run 7^155 Temp. 25.0 Cell F Conc. 0.01271

t (min.) R t (Rgo —R)

0.40 400 192 1.52 420 696 2.72 440 1190 4.00 460 1672 5.40 480 2156 6.95 500 2635 8.67 520 3110 10.55 540 3580 CD 879

-879 I = -9600 kg = -9600 X 0,.01270 Table C X

4-Eydro%y-4-methylpentanoic Aeid Lactone

Run ^249 Temp. 25.0 Cell A Conc. 0.01464

t (min.) R ■fc (Roo “R)

1.43 300 433 3.05 320 863 4.92 340 1294 7.08 360 1720 y . 6 0 360 2131 12.62 400 2562 00 603 ——

I = -5950 t = -603 2 -5950 X 0.01464 TableLXl 17%

5-Hydroxypentanoic Acid Lactone

Run ^106 Temp. -0.05 Cell A Conc. 0,0004068

t (min.) R t (Roo-R)

0.57 20,400 4,919 1.35 2 1 , 0 0 0 10,841 1.95 21,500 14,879 2.98 2 2 , 0 0 0 20,949 3.93 22,500 25,663 5.03 23,000 30,331 6.25 23,500 34,563 00 . 29,030 ------29,030 I = -199,100 = 358 k2 = ■199,100 X 0.0004068

Run #107 Temp.. -0.05 Cell D Conc. 0.0003688

t (min.) R t (Rcb— R)

1.07 23,400 1 0 , 1 1 2 2.13 24,100 18,638 2.80 24,500 23,380 3.53 25,000 27,711 4.70 25,500 34.310 5,78 26,000 39,593 CO 32,850 -----

-32,850 = -269,172 = 341 ^ 2 = -269,172 X 0.0003688 Table L.xi I ^

5-Hydroxypentanoic Acid Lactone

Run if 10 8 Temp. -0.05 Cell E Conc. 0.0003301

t (min.) R t (Roo-R)

1.55 35,900 20,166 2.48 36,700 30.281 3.12 37,200 36,540 3.65 37.600 41.282 4.80 39,000 47,568 5.98 39.600 55,674 00 48,910 -48,910 _ I = -405 , 2 2 0 Ir. — -405,220x0.0003301

Run if 10 3 Temp. 16.1 Cell A Conc. 0.0003250

t (min.) R t (R(x) -R)

0.33 13,900 1660 0.82 14,300 3800 1.08 14.500 4800 1.37 14,700 5820 2 . 0 0 15,100 7680 2.72 15.500 9350 3.82 16,000 1 1 , 2 1 0 00 18,940

-18,940 _ P55 I = -6 8 j165 ‘^ 2 -6 8 ,165 X 0.0003250 îableLXIII 174

5-Eydrori/pentanoic Acid Lact one

Run j f l 0 5 Temp. 16.1 Cell C Conc. 0.0004008

t (min.) R t (Roo-R)

0.55 11,600 2350 1.18 1 2 , 1 0 0 4460 1.80 12,500 6100 2.33 12,800 7180 2.73 13,000 7860 3.18 13,200 8530 00 15,880

I = -42, 128 -16 ,.880 ____ = 940 ^2 ' -42 ,128 X 0.0004008

Run #110 Temp. 16.1 Cell B Conc. 0.0002389

t (min.) R t (Roo-R)

0.73 29,000 5,920 1.52 29,800 1 1 , 1 0 0 2.33 30,500 15,420 2.82 30,900 17,550 3.60 31,500 20,250 5.23 32,500 24,200 00 37,120

I - -165,500 kg - _ie5,500 x 0.0002389 ~ Table LXiv

5-Eydroxypentanoio Acid Lactone

Run #111 Temp. 16,1 Cell C Conc. 0,0002964

t (min.) R t (R„-R)

0.57 16,500 2782 0.85 16,700 3980 1.27 17,000 5560 1.58 17,200 6610 2.08 17,500 8060 3.03 18,000 10,250 00 21,380

I = -81, 347 -21,380 = Rfifi ^ 2 - 31,347 X 0.0002964

Run #101 Temp. 25.0 Cell B Conc. 0.0002642

t (min.) R t (Roo -R)

0.25 22,900 598 0.62 23,100 1358 0.80 23,200 1670 1 . 2 0 23,400 2270 1.65 23,600 2790 2.15 23,800 3205 oo 25,290

I -67,161 kg = _67,161*x 0.0002642 “ Table LX V |

S-Hydroxypentatioic Acid Lactone

Run T^IOS Temp. 25.0 Cell C Conc. 0.0002953

t (min.) R t (Ro o -R)

0.48 13,100 985 0.67 13,200 1308 1.08 13,400 1890 1.58 13,600 2450 2.85 14,000 3280 oo 15,150 — — —

I = 037,368 kg = 150 = -37, 368 X 0.0002953 Tableuxvi

5-Sydroay~2-methylpentatioic Acid Lactone

Run j f l l Z Temp» -0.05 Cell A Gone. 0.001507

t (min.) R t (.Rgg - R)

0.78 7300 6410 1 . 1 0 7500 8840 1.62 7800 12,500 1.97 6000 14, 800 2,35 8200 17,200 2.73 8400 19,450 3.37 8700 23,000 4.07 9000 26,570 4.82 9300 30,000 6.82 1 0 , 0 0 0 37 , 700 00 15,520

: ' ' - 7 9 . M ^ f o . o b l S O '7 ' 1=0

Run if 113 Temp. -0.05 Cell B Cone. 0.0001490

t (min.) R t (Rq j -R)

1 . 1 0 9,800 11,180 1.95 10,500 18,400 2.18 10, 700 2 1 , 0 0 0 2.45 10,900 22.130 3.02 11,300 26,100 3.48 11,600 29,000 4.13 1 2 , 0 0 0 32,800 5.03 12,500 37,400 6.28 13,100 43,500 00 19,940 ——————

I = -80,924 kp = = 165 2 _30,924 X 0.001490 178 T a b l e L X V U

S-Hydroxy-Z-methylpentarioio Acid Lactone

Ran #114 Temp. -0.05 Cell C Conc. 0.001666

t (min.) R t (Roo-R)

0 . 2 2 5558 1531 0.65 5858 4330 0.95 6058 6150 1.45 6358 8930 2 . 0 0 6658 11,704 2.78 7058 15,200 3.45 7358 17,750 4.22 7658 20,450 5.05 7958 20,450 00 12,510 t m mm m I » -49,460 ko = _ -12,510 = IK?. •49,460 X 0.001666

Run #115 Temp- 16.1 Cell B Conc. 0.0008181

t (min.) R t (Roo-R)

0.28 9500 2558 0.72 1 0 , 0 0 0 6214 1.28 10,600 10,278 1.72 1 1 , 0 0 0 13,124 2.42 11,600 17,013 2.98 1 2 , 0 0 0 19,757 3.88 12,600 23,396 4.58 13,000 25,785 5.60 13,500 28,728 6.05 13,700 29,827 00 18,630

I = -62,815 k- = .... 2 -62,815 X 0.0008181 Table L X V U I , ^

5-Eydroxy-2-methylpentanoic Acid Lactone

Run Temp. 16.1 Cell A Conc. 0.0006224

t (min.) R t (R(x,-E)

0.40 8700 3192 0.77 9000 5914 1.15 9300 8487 1.58 9600 11,186 2.03 9900 13,763 2.53 1 0 , 2 0 0 16,394 3.43 10,700 20,511 4.48 1 1 , 2 0 0 24,550 5.18 11,500 26,832 5.43 11,600 27,584 00 16,680

I = -71,544 k" = -16,680 - 2 -71,544 X 0.0006224

Run #117 Temp. 16.1 Cell C Conc. 0.001010

t (min.) R t (R„-R)

0.32 5400 1657 0.58 5600 2906 0.85 5800 4089 1.13 6000 5209 1.43 6200 6306 1.95 6500 8015 3.02 7000 10,902 4.33 7500 13,468 5.00 7700 14,550 00 •10,610 -10,610 I = -28,600 -28,600 X 0 . 0 0 1 0 1 0 " Table LXlx 80

5-Eydroxyrt%8m©thylpentanoic Acid Lactone

Run ^118 Temp» 25.0 Cell A Conc. 0.0005922

; (min.) R t (Roo

0.37 1 0 , 0 0 0 2982 0.85 10,400 6511 1.38 10,800 10,019 1.97 1 1 , 2 0 0 13,514 2.28 11,400 15,185 2.62 11,600 16,925 2.97 11,800 18,592 3.33 1 2 , 0 0 0 20,180 3.92 12,300 22,579 4.38 12,600 23,915 5.57 13,000 28.184 CO 18,060 ——————

I - -83,639 kg = _33^639 x 0.000 59 22 “

Run fll9 Temp. 25.0 Cell B Conc. 0.0005802

t (min.) R t (Roo-R)

0.27 1 0 , 0 0 0 2309 0.57 10,400 4646 0.90 10,800 6975 1.47 11,400 10,511 2 . 1 2 1 2 , 0 0 0 13,886 2.58 12,400 15,867 3.45 13,000 19,148 4.10 13,400 21,115 5.20 14,400 21,580 00 18,550

I = -55,763 -18,550 _ ""2 ' -55, 763 X 0.0005802 Table LX X I 8(

5-Eydroxy"2-methylpentanoic Aoid Lactone

Run #120 Temp. 25.0 Cell C Conc. 0.0006726

t (min. ) R t (Roo-R)

0.38 6200 1946 0 . 8 8 6600 4154 1.15 6800 5198 1.45 7000 6264 1.77 7200 7292 2.30 7500 8786 2.93 7800 10,314 3.67 8100 11,817 4.85 8500 13,677 00 11,380

I = -33,401 ko 2 -33,401 X 0.0006726ne oe = 505 Table LXXI l$Z S-Eydroxyhexanoic Acid Laotone

Run f:127 Temp. -0.05 Cell A Conc. 0.001307

t (min.) R t (Roo-R)

0.25 7000 2140 0.77 7400 6283 1.33 7800 10,321 1,97 8200 14,500 2.65 8600 18,444 3.40 9000 22,304 4.25 9400 26,180 5.72 1 0 , 0 0 0 31,803 00 15,560 ---

I = -68,437 -15,560 _ 2 Y5 ^ 2 -68,437 X 0.001307

Run ^128 Temp. -0.05 Cell B Conc. 0.001490

t (min.) R t (Rq o 'R)

0 . 2 0 9000 2172 0.55 9400 5753 0.90 9800 9054 1.30 1 0 , 2 0 0 12,559 1.73 10,600 16,020 2.42 1 1 , 2 0 0 20,957 3.23 11,800 26,034 5.23 13,000 35,878 00 19,860 -19,800 X I = -74,008 ^ 2 = -74,008 0.001490 Table#.XX11 (83

5-Eydroxyhexanoic Aoid Laotone

Run #129 Temp. -0.05 Cell C Conc. 0.001666

t (mia.) R t (Roo-R)

0.80 ■ 6000 5013 1.42 6400 8330 2.07 6800 11,315 2.83 7200 14,337 3.73 7600 17,404 4.75 8000 20,264 5.35 8200 21,753 00 12,266

I = -37,858 = -12,266 _ kg -39,858 X 0.001666

Run #124 Temp. 16.1 Cell A Conc. 0.0007667

t (min.) R t (Roo-R)

0.28 6800 1705 0.50 7000 2945 0.75 7200 4268 1.27 7600 6718 1.87 8000 9144 2.55 8400 11,450 3.35 8800 13,702 4.82 9400 16,822 CO 12,890

I = -39,236 = _ -12,890 __ _ ^28 kg -39,236 X 0.0007667 Table LXXUI I 84-

5-Hydroxyhezanoic Aoid Laotone

Buu #125 Tez^, 16.1 Cell C Coac. 0.0009465

t (min.) R t (Rq o -R)

0.22 5600 1141 0.65 6000 3111 0.90 6200 4127 1,16 6400 5044 1.75 6800 6976 2.08 7000 7875 2.47 7200 8857 3.30 7600 10,514 3.78 7800 11,287 00 10,786

I = -25,164 kg = _25,164 x 0.0009465 "

Run ^126 Temp. 16.1 Cell B Cono. 0.0008572

t (min.) R t (Rq o -R)

0.35 8500 2910 0.67 8900 5380 1.20 9500 8800 1.62 9900 11,190 1.93 10,200 12,780 2.18 10,400 14,000 3.00 11,000 17,450 00 16,820

I = -46,158 « _____ .-16,820 , = 426 ^2 -46,158 X 0.0008572 Table LX X I V ‘S T

5-Eydrozyhexanolo Acid Lactone

Run f=121 Temp. 25.0 Cell A Cono. 0.0004866

t (min.) R t (Roo-R)

0.37 8500 2560 0.77 8900 5020 1.08 9200 6718 1.57 9600 9137 2.07 10,000 11,219 2.67 10,400 13,403 3.33 10,800 15,385 4.12 11,200 17,386 5.02 11,600 19,176 00 15,420

I = -46,761 kg = -15,420 c Ayp 2 -46, 761 X 0.0004866

Run #122 Temp. 25.0 Cell B Cono. 0.0005802

t (min.) R t (Roo-R)

0.47 10,400 3929 0.75 10,800 5970 1.07 11,200 8089 1.42 11,600 10,167 1.80 12,000 12,168 2.22 12,400 14,119 2.70 12,800 16,090 4.13 13,800 20,489 00 18,760 ——

_18,.760 . g g g I = -49,434 ’=2 ' -49 ,434 X 0.0005802 Table L< X V I

5-Hydro7yhexanoie Aoid Laotone

Run #123 Temp, 25.0 Cell C Conc. 0.0006726

t (min.) R t (Roo-R)

0.30 6200 1605 0,48 6400 2472 0.68 6600 3366 1.13 7000 5142 1.67 7400 6931 2.30 7800 8626 3.07 8200 10,285 00 11,550 —- —-

I = -26,103 = ---- ______= 660 ^2 -26,103 z 0.0006726 Table L-XXVJ I gy

5-Hydroxy«2^dlm9thylpentaaoio Acid Laotone

Run "^25 Temp. -0.05 Cell C Conc, 0.002240

t (min.) R t (Roo-R)

0.80 4600 3510 1.38 4800 5778 2.00 5000 7974 2.72 5200 10,300 3.48 5400 12,483 4.37 5600 14,801 5.37 5800 17,114 5.90 6000 18,213 oo 8987

I » -48,450 = -8987 = flp.fi ^2 -43,450 X 0.002240

Run ^226 Temp. -6.05 Cell D Conc. 0.002391

t (min.) R t (Roo-R)

0.40 4800 1902 0.88 5000 4009 1.40 5200 60 98 1.97 5400 8187 2.58 5600 10,206 3.25 5800 12,207 4.00 6000 14,224 4.82 6200 16,176 5.73 6400 18,084 6.77 6600 20,010 00 9556 — — — — I = -49,700 = -9556 = fln,5 1:2 -49,700 X 0.002391 Table LXXvil I g g

5-Hydroxy-2,2-dimethylpeatanoic Aeid Lactone

Run t^ 30 Temp. -0.05 Cell A Conc. 0.002080

t (min.) R ■fc (l^oo“^)

0.55 5200 2739 1.07 5400 5115 2.27 5800 9943 2.93 6000 12,247 3.68 6200 14,646 4.52 6400 17,086 6.47 6800 21,869 7.65 7000 24,327 00 10,180 -- -

I = -60,650 kg = ,i 180 = 8 0 . 5 ^ -60,650 X 0.002080

Run f222 Temp. -14.0 Cell F Conc. 0.001905

t (min.) R t (Roo-R)

0.62 5000 2430 0.98 5200 3646 1.40 5400 4929 1.85 5600 6142 2.33 5800 7270 2.92 6000 8526 4.72 6500 11,422 00 8920

I = -27,200 k.» = -8920 . ------= 172 -27,200 X; 0.001905 Table LXxvill '81

5"Hydro3qr-2,2“dimethylpeQtatiolo Aoid Laotone

Run #223 Temp. 14.0 Cell E Cono. 0.002056

t (mn.) R t (Roo-R)

0.77 4600 2641 1.17 4800 3779 1 -fiî> snnn iLono 2.12 5200 6000 2.70 5400 7101 3.37 5600 8189 4.18 5800 9321 5.12 6000 10394 00 8050 —

I » 22,800 ko * -8030 . 172 z -22,800 X 0.002056

Run #229 Tesn>. 14.0 Cell F Conc. 0.001755

t (min.) R t (Roo-R)

0.52 5400 2194 0.85 5600 3417 1.25 5800 4775 1.67 6000 6045 2.13 6200 7285 2.65 6400 8533 3.25 6600 9815 00 9620 —

-9620 = 169 I » -32,400 k2 ' -32,400 X 0.001755 Table uxxix j ^

5-Sydrozy-2,2-dlmethylpeotanolo Aoid Laotone

Run #219 Tenç. 25.0 Cell C Cono. 0.001749

t (adn.) R t (Roo-R)

0.95 3000 1706 1.57 3200 2506 2.38 3400 3322 5.42 3600 4090 4.88 3800 4860 7.02 4000 5588 00 4796 —

I » -10,200 -4796 _ ^2 = 10,220 % 0.001749

Run #227 Tezap. 25.0 Cell C Cono. 0.001425

t (min.) R t (Roo-R)

0 .43 3400 1023 0.67 3500 1528 0.92 3600 2006 1.18 3700 2454 1.48 3800 2930 2.17 4000 3863 3.02 4200 4772 4.10 4400 5658 00 5780 —

I - -14,930 --- -5780 B 01^0 ^2 = -14,930 X 0.001425 Table i-XXK | j

5"Hydroxy-2,2~dlmethylpettbaaoio Aoid Lactoae

Run f Z 2 8 Temp. 25.0 Cell D Cono. 0.001745

t (min.) R t (Rq o -R)

0,50 2800 965 0.73 2900 1336 1.28 3100 2086 1.63 3200 2494 2.00 5300 2860 2.43 3400 3232 3.48 3600 3932 4.97 3800 4622 00 4730

-4730 _ I = -9620 k2 = -9620 % 0.001745 Table Lxxxi

5-Hydroxy-5, S-dimethylpeatanoio Aoid Laotone

Run #168 Temp. -0.05 Cell B Cono. 0.01936

t (min.) R t (Roo-R)

1.18 700 1085 2.20 720 1980 3.23 740 2840 4.37 760 3760 5.45 780 4570 6.63 800 5440 9.83 850 7570 12.68 890 9250 15.00 920 10500 00 1620 —

I = -29,136 -1620 . n g„ 1:2 = -29,136 X 0.01936

Run #169 Temp. -0.05 Cell E Cono. 0.02092

t (min.) R t (Roo-R)

0.58 610 483 1.62 630 1317 2.68 650 2100 4.97 690 3740 6.80 720 4910 8.83 750 6120 12.53 800 8060 15.05 830 9210 00 1443 —

. I = -23,880 - M 4 3 . „ k2 = -23,880 I 0.02092 Tabla L)

5»Hydro3y - 3,3-diinethylpen.taaoio Aoid Laotone

Rua #170 Temp. -0.05 Cell F Coac. 0,02188

t (nda») R t (Eoo-R)

1.00 600 796 2.58 630 1980 4.28 660 3160 6.05 690 4270 8.00 720 5410 10.12 750 6550 13.25 790 8050 15.53 820 9150 œ 1396 —

-1396 _ „ I * -22,164 ^ 2 -22,164 X 0.02188

Rua #165 Temp. 16.2 Cell B Coac, 0.01900

t (nda.) R t (Rq q -R)

0.52 420 242 1.15 440 512 1.82 460 774 2.57 480 1040 3.37 500 1295 4.25 520 1550 5.27 540 1820 6.37 560 2075 7.58 580 2310 00 885 —

I = -5264 -885 - 9 95 ^2 = -5264 X 0.01900 Table LXXMI *14

5«flydroxy-»S,3-dlmethylpeD.tanolo Aoid Laotoae

Run #166 Temp. 16.2 Cell E Coao. 0.02095

t (ndn.) R t (Rq q -R)

0.72 380 304 1.40 400 563 2.13 420 810 2.95 440 1075 3.83 460 1305 4.85 480 1660 6.00 500 1810 7.28 520 2045 co 801 mmmm

Rua #167 Temp. 16.2 Cell F Coao. 0,02154

t (nda.) R t (Rq q -R)

0.47 360 187 1.13 380 427 1,85 400 662 .2.80 423 946 4.55 460 1355 5.65 480 1570 6.97 500 1800 œ 758

^2 ' .4089 % 0.02154 ' 19 5" Tabla LXXxiv

5-Hydro:qr"S*S-dlmethylpentanoio Aoid Laotoae

Run #162 Temp. 25.0 Cell B Cono. 0.01367

t (min.) R t (Roo-K)

0.80 460 346 1.32 480 544 1.92 500 752 2.55 520 950 3.23 540 1138 4.02 560 1345 4.87 580 1620 5.85 600 1710 8.92 650 2160 00 892 ——

-892 . , 5 J. ^ ^2 -4222 X 0.01367

Run #163 Temp. 25.0 Cell E Cono. 0.01512

t (min.) R t (Roo-R)

0.73 400 282 1.23 420 450 1.88 440 650 3.27 480 1000 4.12 500 1130 5.08 520 1350 6.18 540 1520 7.47 560 1690 00 786 —

_ -786 _ . I = -3343 ^2 -3343 X 0.01512 Table Lxxxv

5»Hydroxy5,3"dimethylpentanoio Aeld Laotoae

Run #164 Ten^. 25*0 ColX F CoQo* 0 #01562

t (nda.) R t (Roo^)

1.08 400 394 1.73 420 597 2.40 440 780 5.25 460 985 4.12 480 1172 5.15 500 1365 00 765

I « -3511 ^ 2 ' -3511 X 0.01562 Table LXX% VI M y

5-Eydroxy-5"methylhexanoio Acid Lactone

Run ^189 Temp. -0.05 Cell B Cono. 0.02630

t (min.) R t (Roo-R)

0.67 550 545 1.98 559 1590 3.78 575 2979 4.52 580 3539 5.95 590 4600 7.42 600 5661 8.97 610 6754 24.42 695 16,318 38.93 760 25,475 00 1363 —

I = -60,350 V _ -1363 = 0.860 “Z -60,350 X 0.02630

Run i{f:190 Temp. -0.05 Cell E Cone. 0.02760

t (min.) R t (Roo-H)

0.75 495 544 1.40 500 1008 2.82 510 2002 4.27 520 2989 5.68 530 3919 7.25 540 4930 8.88 550 5950 28.37 645 16,315 00 1220 ——

I = -51,560 kg = . -1220_ = 0.855 2 -51,560 X 0.02760 Table LXXXVM ^ &

5-Hydroxy-5»methylhexanoio Acid Lactone

Run ^191 Temp. -0.05 Cell E Cone. 0.02880

t (min.) R t (R^-R)

0.68 480 471 2.08 490 1421 3.53 500 2376 5.00 510 3315 6.53 520 4264 8.17 530 5253 00 1173

I = -47,300 ko = . -1173 ___ _ 0.860 Z -47,300 X 0.02880

Run ^186 Temp. 14.0 Cell B Cone. 0.02420

t (min.) R t (Roo-R)

0.60 360 258 1.47 370 617 2.32 380 951 3 » 33 390 1332 4.38 400 1708 5.48 410 2082 00 790 -790 I = -12,960 kq 2 -12,960 X 0*02420 Table LKX.XVIU I

5-Hydroxy-5-methylhexapoic Acid Lactone

Run ^187 Temp» 14.0 Cell E Cone. 0.02720

t (min.) R t (Rq o -R)

0.53 310 196 1.42 320 510 2.38 330 831 3.40 340 1152 4.52 350 1487 5.72 360 1825 00 679 ——“ -679 I = -9880 ^2 -9880 X 0,.02720

Run #188 Temp. 14.0 Cell F Cone. 0.02840

t (min.) R t (Roo-R)

0.43 300 155 1.52 310 462 2 « 33 320 802 3.35 330 1106 4.43 340 1418 5.60 350 1736 oo 660 —

I = -9265 V, - -660 - ? Rn 2 -9265 X 0.02840 “ 7^0 0 Table L)CXK|X

5-Bydroxy-5-methylhexatioic Aoid Lactone

Run ^183 Temp. 25*03 Cell A Cone. 0.01415

t (min.) R t (Roo-E)

0.83 300 256 1.83 310 547 2.88 320 832 4.07 330 1136 5.28 340 1420 6.65 350 1722 00 609 —

I = -8690 = -609 _ , -8690 % 0.01415

Run 1^184 Temp. 25.03 Cell A Cone. 0,01930

t (min.) R t (Roo-E)

0.40 225 97 1.33 235 310 2.38 245 531 3.53 255 752 4.80 265 974 6.25 275 1206 oo 468 — — —

I = -5020 kg = -468 _ ^ 2 -5020 X 0.01930 ° ^ol

Table XC

S-BydroayS-methylhexanoio Aoid Lactone

Run -^185 Temp, 25*03 Cell D Cone. 0.01795

t (min.) R t (Roo-R)

0.30 250 31 1.22 260 318 2.18 270 547 3.25 280 785 4.42 290 1021 5.72 300 1264 00 521 --

I = -4440 -521 4.95 ^2 -4440 X 0.01795 Table XCI

S-Hydroxyheacanoic Aoid La et one

Rua #171 Temp. -0.05 Cell A Coao. 0.01390

t (min.) R t (Rcd-K)

0.15 680 153 0.58 710 573 0.75 720 734 1.05 740 1006 2.52 825 2200 3.00 850 2544 4.05 900 5232 6.57 1000 4586 00 1698 -—

= -9350 -1698 = 13.1 kg =.—Overt V A Aivor

Rua #172 Temp. -0*05 Cell C Coao. 0.01650 t (mia.) R t (Roc-H)

0.38 600 328 0.68 620 575 0.98 640 807 2.00 700 1526 2.48 725 1830 3.53 775 2429 4.73 825 3018 6.92 900 3896 00 1463 — — — -1463 I ~ —6880 = 12.9 -6880 X 0.01650 T a b l e X G 11 ^ ^ 3

6-Hydroxyhexanoio Acid Laotoae

Run #173 Temp. -0.05 Cell D Cone. 0.01900

t (min.) R t (Ro o -R)

0.22 510 167 0.50 530 369 0.80 550 i 574 1.62 600? 1081 2.55 650 1573 3.65 700 2070 4.93 750 2549 6.47 800 3021 00 1267 ——-

I = -4920 k, = '1267 . _ = 13.5 -4920 X 0.01900

Run #174 Temp. 14.0 Cell 3 Cone. 0.006650

t (min.) R t (Roo-R)

■ 0.28 1219 277 0.70 1239 671 0.90 1269 844 1.13 1289 1037 1.88 1350 1611 2.55 1400 2058 3.32 1450 2513 4.17 1500 2948 5.12 1550 3364 6.20 1600 3763 oo 2207 ——

I = -11,200 y ^ -2207 . = 29.7 -11,200 X 0.006650 Table XCIM

6-Hydroxyhexanoio Aoid Laotoae

Run = § ^ 1 7 5 Temp. 14.0 Cell E Cono. 0.007920

t (min.) R t (Roo-R)

0.50 1020 586 0.95 1075 1060 1.20 1100 1309 1.67 1150 1738 2.22 1200 2200 2.82 1250 2654 3.47 1300 3092 4.20 1350 3532 5.02 1400 3971 5.92 1450 4387 00 2191 ---- -2191 « I = -8570 ^2 “ -8570 X 0.007920

Run j r l 7 6 Temp. 14.0 Cell F Conc. 0.009160

t (min.) R t (Roo"^)

0.43 875 415 0.90 925 824 1.42 975 1230 1.97 1025 1608 2.98 1100 2208 3.35 1125 2399 4.20 1175 2797 5.15 1225 3172 6.30 1275 3566 00 1841 — — — —

I = -6290 k2 = _g29Q ^ 0.009160 Table XCl'v'

6-Eydroxyhexanoio Aoid Lactone

Run ffl80 Temp. 25.0 Cell A Cono. 0.006610

t (min.) R t (Ro o -R)

0.27 625 157 0.78 675 415 1.40 725 675 2.17 775 937 3.10 825 1184 4.27 875 1418 5.02 900 1541 00 1207

- -1207 - 59 0 I — —3085 ^2 -3085 X 0.006610 °

Run fl82 Temp. 25.0 Cell D Conc. 0.009140

t (min.) R t (Ro o -R)

0.27 475 131 0.75 525 327 1.35 575 521 2.12 625 712 3.17 675 907 4.63 725 1093 5.58 750 1177 00 961 ---

I = -1750 -961 - e n -I kg = -1750 X 0.009140 Table % C V X0(>

6-Hydroxyheptanoio Aoid Laotoae

Run fgl3 Temp. -0.05 Cell A Conc. 0.02720

t (min.) R t (Roo-R)

0.88 400 474 2.40 440 1198 3.27 460 1566 4.22 480 1937 5.25 500 2305 6.32 520 2648 7.60 540 3032 8.93 560 3384 00 939 3384 -939 5.02 I = -6870 ^2 -6870 X 0.02720

Run ^14 Temp. -0.05 Cell A Conc. 0.02840

t (min.) R t (Roo-R)

0.67 380 344 1.38 400 682 2.12 420 1005 2.97 440 1348 3.87 469 1680 4.87 480 2016 5.98 500 2356 7.20 520 2693 9.28 550 3192 00 894 -894 I — —6060 5.19 ^2 -6060 X 0.02840 ” TableXCVi ^ 6 /

6-Hydroxyheptanoic Aoid Lactone

Run ^‘215 Temp. -0.05 • " Cell C Conc. 0.02980

t (min.) R t (Roo-R)

0.28 360 144 0.95 380 468 1.67 400 790 2.43 420 1101 3.30 440 1439 4.22 460 1743 5.23 480 2055 6.40 500 2387 9.10 540 3030 00 875 —— -873 I = -5630 ^2 " -5630 X 0.02980 “ 5.20

Run 1^206 Temp. 14.0 Cell A Conc. 0.02677

t (min.) R t (Roo-R)

0.40 240 122 0.97 260 276 1.62 280 429 2.37 300 581 3.27 320 736 4.32 340 886 5.62 368 1040 7.08 380 1168 10.27 410 -410 I = -1715 ^2 ■ -1715 3: 0.02677 ~ 1^*90 \

Ao8 Table XC vu

6-Hydroxyheptaaoio Acid Lactone

Run f207 Temp. 14.0 Cell A Conc. 0.02806

t (min.) R t (Roo-E) / 0.42 240 114 0.97 260 244 1.63 280 378 2.42 300 513 3.37 320 647 4.50 340 774 5.97 360 907 10.35 400 1159 00 512

I = -1490 - “512 = o ^2 -1490 X 0.02806

Run f208 Temp. 14.0 Cell C Conc. 0.02933

t (min.) R t (Roo-^)

0.62 240 164 1.38 270 323 1.73 280 368 2.55 300 520 3.48 320 640 4.67 340 766 6.12 360 881 8.05 380 998 00 504 — — — -504 I = -1390 ^2 - -1390 X 0.02933 " ^^.3 Table XCYUI

6-Hydroxyheptagoic Aoid Lactone

Run #210 Temp. 25.07 Cell B Cono. 0.01145

t (mia.) R t (Roo-R)

0.28 600 159 0.60 620 329 0.92 640 487 1.27 660 646 1.65 680 807 2.07 700 971 3.23 750 1353 4.73 800 1745 oo 1169 _ -1169 I = -4610 ^2 -4610 r 0.01145 "-'1

Run #211 Temp. 25.07 Cell E Conc. 0.01280

t (min.) R t (Roo-R)

0.38 520 183 0.73 540 338 1.10 560 487 1.48 580 626 1.93 600 778 2.40 620 919 2.93 640 1064 3.53 660 1211 4.18 680 1350 oo 1003 —— —

I = -3625 kn = -1003 = 22.1 2 -3625 % 0.01280 Jl I O Table XCIX

6-Hydroxyheptaaois Aoid Laotoae

Eun #212 Temp. 25.07 Cell F Coao. 0.01410

t (mia.) R t (^00

0.58 480 250 0.93 500 382 1.32 520 516 1.75 540 649 2.23 560 783 2.77 580 917 3.35 600 1042 4.03 620 1173 4.80 640 1300 00 911 —- -911 I = -2940 22.1 2 -2940 X 0.01410 AÜTOBIOGRAPHÏ

I, Thomas John Dougherty, was born in Buffalo, New York, on

August 2, 1933• I received m y elementary and secondary school education in the public schools of Buffalo, Nevr York. On June 12,

1955,1 received a Bachelor of Science degree from Canisius College,

Buffalo, New York. I entered the graduate school of The Ohio

State University in September, 1955» While conçleting the require­ ments for the degree Doctor of Philosophy I held appointments as

Teaching Assistant, Research Assistant, Fellow of the Standard Oil

Conçany of Ohio and of the National Science Foundation.

211