A Study Op the Kinetics Op Hydrolysis Op

A STUDY OP THE KINETICS OP HYDROLYSIS OP

CYCLOALKANONE DIALKYL KETALS

DISSERTATION

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

WALTER THOMAS REICHLE, B.S.

The Ohio State University

1958

Approved by:

Adviser Department of Chemistry ACKNOWLEDGMENTS I I wish to express my deep apprecia tion for the guidance, help, and advice which I have received from Dr. Harold

Shechter during the course of this investi gation.

I am grateful to the General Electric

Company and the National Science Foundation for fellowship funds. I also wish to thank the taxpayers of the State of Ohio and those of the United States of America for their liberal, indirect aid.

ii DEDICATED To

H.S.S. and

My Wife, for the many lonely hours.

iii TABLE OP CONTENTS

Page

I, INTRODUCTION ...... 1

II. THE MECHANISMS OP THE HYDROLYSIS OF ACETALS AND K E T A L S ...... 4

III. DISCUSSION OF RESULTS OF THE PRESENT INVESTIGATION ...... 19

The Kinetics of Hydrolysis of Homologous Cyclanone Dimethyl K e t a l s ...... 19

The Effect of the Alcohol Groups on the Rates of Hydrolysis of Cyciobutanone, Cyclopentanone, and Cyclohexanone Dialkyl Ketals ...... 33

The Effect of Alkyl Groups on the Rates of Hydrolysis of Methyl Ring-substituted Cyciobutanone, Cyclopentanone, and Cyclohexanone Dimethyl K e t a l s ...... 43

Free Energy Relationships of Reactions of Cyclic Molecules ...... 58

IV, EXPERIMENTAL

Constant Temperature B a t h ...... 6? Temperature Measurements ...... 68 Miscellaneous ...... 69 Kinetic Procedure ...... 71 Calculations ...... 75 Special Calculations for the Hydrolysis of the Ten-membered Ketal . . 77 Activation Energy and Entropy Calculations 78

Preparation and Purification of Chemicals . 80 Solvent Preparation ...... 80 Catalyst Solutions ...... 81 Solvent Densities ...... 82

iv • TABLE OP CONTENTS (Continued)

Page

IV. (Cont inued)

Preparation and Purification of Ketones . . . 83

Cyclopentanone...... 83 Cyclohexanone ...... 83 Cyclofteptanone...... 83 Cyclooctanone ...... 83 Cyclononanone ...... 83 Cyclodecanone ...... 83 ®i-n-hexyl k e t o n e ...... 85 3.3-Oimethylcyclopentanone ...... 85 3 .3-Difflsthylcyclohexaiion e ...... 85 2-Methylcyclopentanone ...... 85 ©i-n-propyl ketone ...... 85 Cyciobutanone ...... 85 3 »3>5,5-Tetramethylcyclohexanone ...... 86 2-Methylcyclohexanone ...... 86 2.2,^,4-Tetramethylcyclobutanone ...... 87 Cyclodecanone ...... 9 Q Cyclododecanone ...... 90 Cyclotetradecanone ...... 90 Triisopropyl orthoformate ...... 91

Preparation and Purification of Ketals .... 92

General procedure illustrated with 2-fflethylcyclohexanone dimethyl ketal . . . 92 Cyclodecanone dimethyl ketal ...... 96 Cyclodecanone methyl enol ether ...... 97 2 . 2 , ^ , Tetramethylcyclobutanone dimethyl ketal ...... 99 Cyciobutanone diisopropyl ketal ...... 99 Cyclotetradecanone dimethyl ketal ...... 99

APPENDIX A— Figures 7 through 1 5 ...... 101

APPENDIX B— Infrared spectra of ketals ...... Ill

APPENDIX C— Tables: Numerical Data ...... 125

5 y LIST OP FIGURES

Figure Page

1. Relative Rates of Reactions ...... 23 ( a , t> , c)

2. Conformations of Cyclodecane and Cyclodecane Cation ...... 31

3-5* Free Energy Plots

3* Cyclanone Ketsl Hydrolysis vs. 1-Ghloro-l-Methyl Cycloalkane Hydro lysis...... 60

Cyclanone Ketal Hydrolysis vs. Cyclanoie Tosylate Acetolysis ...... 62

5. Cyclanone Cyanohydin Equilibrium vs. Cyclanone Ketal Hydrolysis ...... 63

6. Reaction V e s s e l ...... 70

7-11 Activation Energy Plots for Hydrolysis of Cyclanone Dialkyl Ketals, etc...... 102-106 A - A 12-15 Representative Plots of In ~ vs. Time for Hydrolysis 00 ^ Of Ketals ...... 107-110

Infrared Spectra of Ketals ...... 112-124 LIST OF TABLES

Table Page

1. Relative Rates of Hydrolysis of Various Dis.lkyl K e t a l s ...... 9

2. Relative Rates of Hydrolysis of Various Dialkyl Formale ...... 10

3* Ionization Constants of Cycloalkyl- carboxylic Acids in Water ...... 15

4. Ionization Constants of m-Cyclo- alkylbenzoic Acids in Aqueous Ethanol . 16

5. Reaction Velocity Constants and Relative Rates of Hydrolysis of Homologous Cyclanone Dimethyl Ketals ...... 20 6. Activation Parameters for Acid-Catalyzed Hydrolysis of Homologous Cyclanone Dimethyl Ketals ...... 21

7. Activation Parameters of Hydrolysis of Cyclanone Dimethyl Ketals and Acetolysis of Cyclanol Tosylates...... 3^

8. Rates of Hydrolysis of Di&lkyl Ketals of Cyciobutanone, Cyclopentanone, and Cyclohexanone...... 35

9. Relative Rates and Activation Parameters for Hydrolysis of Dimethyl, Diethyl, and Dilsopropyl Ketals of Cyciobutanone, Cyclopentanone, and Cyclohexanone ...... 36 10. Relative Rates of Hydrolysis of Dialkyl Ketals of Cyclanones and Formaldehyde . . . 38

11. Hemiketal Equilibrium Constants of Cyclanones with Methanol and Ethanol . . . kZ

12. Rate Constants of Hydrolysis of Methyl-substituted Cyclanone Dimethyl K e t a l s ...... Jji}.

vii LIST OP TABLES (Continued)

Table Page

13• Relative Rates of Hydrolysis and Kinetic Parameters of Methyl- substituted Cyclanone Dimethyl Ketals . . 43

14. Relative Rates of Hydrolysis of Cyclic Ketals ...... 46

15. Relative Rates of Hydrolysis of Methyl-substituted 1-Chloro- 1-Methylcyclohexanes ...... 46

16. Relative Rates of Methyl-substituted Cyclanone Dimethyl Ketals ...... 4?

17. Relative Rates of Saponification of L a c t o n e s ...... 48

18. Absolute and Relative Equilibrium Constants for Reaction of Ketone and hydrogen Cyanide ...... 49

19. Absolute and Relative Equilibrium Constants for the Ketone-Alcohol- Hemiketal Equilibria ...... 50

20. Rates of Hydrolysis of Open-Chained Diethyl Ketals and Acetals ...... 50

21. Physical Properties of Ketones ...... 84

22. Physical Properties of Ketals ...... 93

23-95 Numerical Data of Ketal Hydrolysis Reactions 126-198

viil INTRODUCTION

In recent years much attention has been devoted to determining the properties of cyclic molecules. While a number of general rules exist which permit a qualitative estimate of some of the thermodynamic and kinetic proper ties more data are required to extend and refine the theo ries .

The acid-catalyzed hydrolysis of ketals of cyclanones (Equation 1), a reaction devoid of side reactions

ii-i ORo R-k ^ 3 + H^O

3 3 .3 ;? water (71.5 mole % water) mixtures, using dilute hydrochloric acid as catalyst. The kinetic entropies, enthalpies, and free energies were calculated from these data.

The diethyl and diisopropyl ketals of cyciobutanone, cyclopentanone, and cyclohexanone have been hydrolyzed to determine the effect of the alcohol group of ketals on the reaction rates. 1 The rates of hydrolysis of the dimethyl ketals of

cyciobutanone through cyclodecanone, as well as cyclodo-

decanone and cyclotetradecanone, have been determined. For

comparison two open-chained ketals— di-n-propyl ketone

dimethyl ketal and di-n-hexyl ketone dimethyl ketal— have

also been hydrolyzed.

While considerable effort has been expended in

determining the properties of homologous four- to seven-

membered ring compounds, relatively little information is

available concerning the kinetic and thermodynamic prop

erties of cyclic compounds which have substituents in

certain parts of the ring. Knowledge of these properties

of substituted cyclic compounds xvould serve as a test of

the current theories of reactivity of cyclic compounds and possibly place the theoretical ideas on firmer basis.

In order to determine the effects of substituents

on the kinetics of reaction of ketals of cyclanones, di methyl ketals of the following ketones have been hydrolyzed

2 ,2,4,4— tetramethylcyclobutanone, 2-methylcyclopentanone,

3 ,3 -dimethylcyclopentanone, 2-methylcyclohexanone, 3 j3 -bi- methylcyclohexanone, and 3 »3>5 ,5 -tetramethylcyclohexanone.

Rate constants and kinetic parameters of these systems were thus obtained. Empirical free energy relationships (Hammett and

Taft type) have become quite important in correlating many organic reactions. It was a further objective of the pres

ent study to determine whether there is a free energy relationship between the hydrolysis of ketals of cyclanones and other kinetic and thermodynamic properties of cyclic molecules; for example, the hydrolysis of 1-chloro-

1 -methylcycloalkanes and the acetolysis of cyclanol tosyl- THE MECHANISMS OP THE HYDROLYSIS

OF ACETALS AND KETALS

Acetals and. ketals, in the presence of water and a

strong acid, hydrolyze quantitatively to the corresponding

aldehydes and ketones (Equation 2 ). Because of the

H® Rf nn Rl ;cr 3 + h9q --- * 3c = o + 2R0OH (2 ) R2 s0R3 <--- R2 J reversibility of this reaction it is possible to synthesize

certain acetals and ketals, provided the water which is formed in the reaction, is removed. Hemiacetals or hemiketals are intermediates in this reaction (Equation 3)*

Rq n Rq OR3 = 0 + R3OH ---- > 'C (3 ) r2 ^ Kj? 'OH

The reactions represented by Equations 2 and 3 occur readily

Normally the concentrations of acid catalyst required is very low (<0.01 N). Also, these reactions can generally be carried out at or below room temperature.

The presently accepted mechanism for acid-catalyzed hydrolysis of acetals and ketals is detailed (Equations 4-

S) as follows: H®

E^0B3 + H® -12^ H^0E3 C •"------— 0R2 + RoOH (5) R? bRp < ------R 5 ^ J * fast 2

fast + BUO ^ E ^ O B 3

E1 fast Blv Aq _ --- >. = 0 + H + Ro0H (7) R 2 OR^ "^sTovT- Rjf j

%f° -£Sf^ V ” + H® ,8 ) *2 3 ^fast R2 ^H3

The hydrolysis of acetals and ketals" has been

•» Acetals are chemically derived from aldehydes, while ketals are derivatives of ketones. Chemical Abstracts used the word acetals for both of these classes of compounds. Since the present investigation is concerned with cyclanone derivatives, the word ketal will be used to refer to these compounds. The mechanisms of hydrolysis of acetals and ketals are essentially identical. Ketals may be conceived as consisting of ketone and alcohol portions, since they hydrolyze to these products.

ketone alcohol portion portion Nomenclature based on this relationship will be used in this dissertation. investigated In some detail. The data which support the reaction mechanism are summarized below.

Skrabal and associates (1,2) were the first to

(1) A. Skrabal and A. Schiffer, Z. phys. Chem., 22, 290 (1921).

(2) A, Skrabal and K. H. Mirtl, Z. phys. Chem., Ill, 98 (192*0. investigate the hydrolysis of simple ketals in some detail.

It was found that the hydrolysis of dimethyl formal was acid-catalyzed and that the rate of formation of formalde hyde, at constant acid concentration, followed a first order law. The rate of hydrolysis was also first order in concen tration of acid. Subsequent studies (3**+) showed that the

(3) J* N. Bronsted and W. P. K. Wynne-Jones, Trans. Faraday Sec., 22s 59 (1929), (4) J. N. 3ronsted and C. Grove, J. Am. Chem. Soc., 22, 139*4- (1930). catalysis by hydrogen ion was specific, e.g., only H was active in promoting the reaction. Numerous other investi gators (5 *6 ,7 ,8 ) have shown that the first order rate of

(5) M. M. Kreevoy and E. W. Taft, Jr., J. Am. Chem. Soc., ZZs 3 1 4 6 (1955). (6 ) D. McIntyre and F. A. Long, J. Am. Chem. Soc., 7.6 , 3240 (1954). (?) D. McIntyre and P. A. Long, J. Am. Chem. Soc., 26, 3243 (1954).

(8 ) P. M. Leininger and M. Kilpatrick, J. Am. Chem. Soc., 61, 2510 (1939).

ketal hydrolysis has an HQ dependence in strongly acid

media. This indicates that the activity of water is not

involved in the rate-determining step of the reaction, or previous to it.

The fact that (5>9) the second order rate constant

(9) >/• J- C. Orr and J. A. V. Butler, J. Chem. Soc., 330 (1937). for the hydrolysis is larger by a factor of three in deuter

ium oxide indicated that a deuteron or a proton is involved in an equilibrium which precedes the rate-determining step of the reaction.^’ Ketal hydrolysis also exhibits a primary salt

Deuterium oxide is more acidic than water; the equil ibrium involving ketal _ _ D + S D S® will be further to the right than the corresponding equil ibrium in water. Hence, the hydrolysis reaction Will be faster because of the higher concentration of D S .

effect (1 0 ).**

(10) L. C. Elesch and M. Kilpatrick, J. Phys. Chem., 12, 561 (1935). 8

When neutral salts are added to the hydrolysis reaction the rate constant increases. This deviation is due to the change in ionic strength of the solution which in turn affects the activity coefficients of the reagents and, presumably, the activated complex.

Evidence has been obtained which indicates that the hydrolysis proceeds by fission of the ketone carbon-oxygen bonds and that alkyl carbonium ions are not involved. Thus, acid-catalyzed hydrolysis of ketals of optically active

2-octanol (1 1 ), 2 ,3 -t>utanediol (1 2 ), and 2-butanol (1 3 ) gave alcohols in which the specific rotations and absolute

(11) J. M. O'Gorman and H. J. Lucas, J. Am. Chem. Soc., 22, 5 4 8 9 (1950). (12) H. K. Garner and H. J. Lucas, J. Am. Chem. Soc., 2 2 , 5 4 9 ? (1950). (13) E. E. Alexander, H. K. Busch, and G. L. Web ster, J. Am. Chem. Soc., 2it» 3 1 7 3 (1952).

configurations were identical with that from which the ketals were derived. Hydrolysis of neopentyl acetal of benzaldehyde (14) occurs without rearrangement to give

(14) C. A. MacKenzie and J. K. Stocker, J. Am. Chem. Soc., 2Z> 3 1 4 8 (1955). neopentyl alcohol and benzaldehyde. Hydrolysis of various “I Q acetals in C4 enriched water (1 5 ) yields alcohols of normal iso topic content.

(15) P. Stasiuk, V. A. Sheppard, and A. N. Bourns, Gan. J. Chem., 34_, 123 (1956).

The rate of hydrolysis of ketals is very sensitive to substituents on the aldehyde or ketone portion of the molecule (Table 1, 16,17). The effect of varying: the

TABLE 1

Relative Rates of Hydrolysis of Various Diethyl Ketals (16,17)*

0 R-i - C E2 Relative Rate R 1 r2 H H (1.00) CH3 H 6.0 x io 3 CH3CH2 H 6.5 x io 3 ( CH3 ) 2 ch H 4.0 x lo 3 (ch3 )3c H 4 . 6 x io 3 (CH3)2CHCH2 H 4 . 0 x 10J C1CH2 H °.25 „ CH3 CH3 1.8 x 10?

4f- In 5 0 : 5 0 dioxane-water by weight, 30°.

(16) M. K. Kreevoy and R. V/. Taft, Jr., J. Am. Chem, Soc., 2Z, 5590 (1955). (17) A. Skrabal and M. Zlatewa, Z. phys. Chem., 119, 305 (1926). 10 alcohol is summarized in Table 2 (18). These data illus trate the considerable increase in the reaction rate when

TABLE 2

Relative Estes of Hydrolysis of Various Dialkyl Formals (18)

Eelative nates Alkoxide Group (in water solution, 25°)

CH^O - (1 .0 0)

CH^CHgO - 8.5 (ch^)2gho - ^7.2

(ch3 )2chch2 q- 13.0

(18) A. Skrabal and H. H. Eger, Z. phys. Chem., 122. 3^9 (1926).

electron donors (by both induction and hyperconjugation) are added to the ketone and the alcohol portion of a ketal.

The facts presented support the mechanism (19> Equa tions to 8 ) for acid-catalyzed hydrolysis of ketals in

(19) C. K. Ingold, "Structure and Mechanism in Organic Chemistry," Cornell University Press, Ithaca, New York, 1 9 53 > P. 33^. aqueous media. Equations 5j and 6 give a pseudo-first-

order rate law, first order in appearance of ketone 11 and first order in proton concentration (in dilute acids; in strong acids this becomes an HQ relationship). In the rate determining step (Equation 5), there is a change in the coordination number on carbon from four to three at the reaction site. Cleavages involve the carbonyl-oxygen bonds and, thereby, do not give alkyl carbonium ions which race- 1 R mize, rearrange, or react with H20 . The prototropic equilibrium precedes the rate-determining step of the reac tion and (Equa.tlon 5) the activity cf a water molecule is not Involved prior to or during the rate-determining step of the reaction. A carbonium ion intermediate, in the rate- determining step, as illustrated (Equation 5)» responds strongly to inductive and hyperconjugative effects. This carbonium ion is strongly stabilized by the adjacent oxygen p-electrons (Equation 9) and experimentally no rearrangements

\ $> •• \ ® . p 0 k— ^ p ^ = 0 (9) of It have been observed.

Hydrolysis of ketals involves a multistep reaction, the first of which is a rapid, reversible protonation (Equa tion 1 0 ), the second a slow and rate-determining unimolecular H® v ,°0H? ® kl fas? . J + IT > X: J (10) X OCH^ -1 dissociation of the conjugate acid of the ketal (Equation 11) 12

H® v OGHq k ? Blow, r.a. . $ X C 2 > )C— OCHo + CHoOH (11) / ' o c h 3 <=• fast A 3 3

and subsequent rapid reactions which give heraiketal and finally ketone, alcohol, and catalyst (Equation 12).

\ £“ ^ q S t rt-J- i C - 0 CH3 + H20 ___; Hemiketal "£? = 0 +

CH^OH + H20 (12)

On the basis of the above mechanism the over-all reaction rate constant (k) is composed of two parts,

* - y ^ 0 3 ) and k2 , and is expiressed by

k! k = x k2 = K k2 o 1*)

The over-all rate constant (k) is therefore not only depend ent upon the rate constant of the rate-determining step (k2 ) but also upon the equilibrium constant (K) of the protona tion reaction.

The equilibrium constant depends on—

a) Steric effects, the influence of b u l k near the reaction site on the concentrations of protonated and unprotonated ketal, 13 b) Polar effects, the Influence of the electronega

tivity of the alkoxyl oxygen on the concentrations of

protonated and unprotonated ketal.

There appears to be little steric influence involved

in the hydrolysis of open-chained ketals (16). Bulk, on

the ketone portion of the ketal, has a steric effect on the

reaction only when the "six-number" (20), relative to the

alkoxyl oxygen, is fairly large. Thus, the diethyl ketal

(20) M. 3. Nev/man, Eec. Chem. Frog. Kresge-Kooker Sci. Lib., 11, 111 (1952).

This author restricts the "six-number" concept to additions to ca,rbonyl compounds. It seems possible to ex tend this concept to the ketal hydrolysis reaction. The numbering starts on the ketal oxygen atoms.

of 3 ~me'thylbutanal ("six-number" of six) hydrolyzes at a rate

predicted by the polar substituent constants cr* (2 1 ) for

(21) R. W. Taft, Jr., "Separation of Polar, Steric, and Resonance Effects in Reactivity," Chapter 13; of M. S. Newman, "Steric Effects in Organic Chemistry," John Wiley and Sons, Inc., New York, N. Y. , 1956.

# Taft reported (reference (21), p. 639) that the rates of hydrolysis of acetals and ketals follow an expres sion (Equation 15) which relates the free energies of acti vation to the sum of the independent contributions of the polar (2cr*P'"') and hyperconjugative ( (n-6 )h) effects of the substituents of the ketone portion of the molecule.

A F * a log k/kQ = (^g**) P* + (n-6 )h (1 5 )

p* was 3.60 for acetals and ketals and h = 0 .5 ^. 14 hydrogen and the isobutyl radical,'" while the diethyl ketal

* bee previous page.

of 3,3-dimethylbutanal ("six-number" of nine) hydrolyzes approximately twenty times as fast as that predicted by the polar substituent constants for hydrogen and the neopentyl group. The maximum "six-number" of the dimethyl ketals of unsubstituted cyclanones is four; this number does not have much significance, however, since the substituents on the cyclanone ring are tied back and cannot interact as effec tively with the alkoxide oxygens as can the substituents in corresponding open-chained compounds. It is thus perhaps to be expected that steric hindrance does not play a significant role In the ketal protonation equilibrium in the hydrolysis of simple cyclanone ketals.

These arguments leave the polar effect as the princi pal one which may influence the equilibrium appreciably. In the larger rings (five-membered and larger) the polar factors are essentially constant, and the equilibrium constants in volving protonated ketals should not vary appreciably with •* ring size.

4f* Steric inhibition of hyperconjugation probably does not play an important role. In cyclanone ketals the number of hydrogens adjacent to the reaction site remains constant, yet their steric orientation relative to the empty p-orbital 15 of the developing transition state does not. The C-Hcr-orbital(s), and the empty p-orbital (of the carbonium ion) should be parallel. H. H. Jaffe and J. L. Eoberts (J. Am. Chem. Soc., 21, 391 (1957) ) point out, however, that there should be only a small change in the hyperconjuga tion because of improper overlap of the orbitals. The C-H orbitals, vihich are not in a proper steric orientation for overlap to occur, do contribute partially to the total C-H hyperconjugative stabilization.

The polar effects in four-, five-, and six-membered rings are not knoxvn. The differences in the ionization con stants of the cycloalkylcarboxylic acids are fairly small

(Table 3). Benzoic acids having cycloalkyl groups in the

TABLE 3

Ionization Constants of Cycloalkylcarboxylic Acids in Water (approx. 0.1 M in NaCl, 22) _ J=rT=r.,_.. = R-— C— OH K a x 105

E = methyl 1.8 Cyclopropyl 1.49 Cyclobutyl 1 .6 4 Cyclopentyl 1.03 Cyclohexyl 1.25

(22) M. Kilpatrick and J. G. Morse, J. Am. Chem. Soc., 21, 1 8 5 ^ (1953). meta-positIon have virtually no differences in their pKa's in 50^ ethanol (Table 4, 23).

(2 3 ) T. P. Corbin, Ph.D. dissertation, The Ohio State University, 1956, pp. 56-57* TABLE 4

Ionization Constants of meta-Cycloalkylbenzolc Acids in 50% Aqueous Ethanol (23)

meta-s.lkyl group pKa (25°) hydrogen 5.696 cyclopropyl 5.850 cyclobutyl 5-889 cyclopentyl 5.922 cyclohexyl 5.929

The data of Tables 3 and. 4 indicate that the polar effects of small rings cannot be large and do not vary much with ring size.

It may thus be concluded that there are probably no major differences in the protonation equilibria (Equation

1 0 ) in the hydrolysis of unsubstituted cyclanone dimethyl ketals. This means that the differences in the rate con stants reflect almost entirely differences in rates of the slow, rate-determining step (Equation 11) of reaction.

Two other reactions of homologous cyclic compounds in which there is unimolecular dissociation in the rate- determining step have been investigated. These are the acetolysis of cyclanol tosylates (24,25) and the hydrolysis of

1-chloro-l-methylcycloalkanes (26). Acetolysis of the tosy lates involves transannular rearrangement in medium-sized

(24) H. C. Brown and G. Ham, J. Am. Chem. Soc., 78, 2 7 3 5 (1956). 1? (2 5 ) R. Heck and V. Prelog, Helv. Chim. Acta, 38, 15^1 (1955).

(26) H. C. Brown and. M. Borkowski, J. Am. Chem. Soc., 24, 1894 (1952).

rings (eight- through eleven-membered; 27,28), To what

V / (2 7 ) V. Prelog and S. Borcic, Helv. Chim. Acts., 41, 199 (1958).

(28) V. Prelog, Angew. Chem., 20, 145 (1958).

extent, if at all, trans&nnular effects accelerate the reaction is not clear. The acetolysis of the four-membered

* There is no deuterium effect (28) in acetolysis of 5,5»6 ,6-tetradeuterocyclodecyl tosylate. There is e sig nificant effect of the gem-dimethyl group on the rate of acetolysis of 5 ,5-dimethylcyclononyl tosylate (547& slower than the unsubstituted tosylate) (29).

(29) A. T. Blomquist.and Y. C. Meinwald, J. Am. Chem. Soc., 80, 630 (1958). ring is accompanied by extensive rearrangement which appar ently increases the reaction rate above that expected for this reaction on a four-membered ring without rearrangement

(30).

(3 0 ) J. D. Roberts and V. C. Chambers, J. Am. Chem. Soc., 21, 5034 (1951).

The products of hydrolysis of 1-chloro-l-methyl- 18 cycloalkanes have not been isolated to demonstrate unequiv ocally the absence of rearrangements in the four-membered ring or of products due to transannular reactions in the medium-sized rings. The hydrolysis of ket&ls does not in volve rearrangements. In the present investigation the four-membered ketones viere "reclaimed" in high yield as the semicarbazones from the ketal hydrolysis liquors. Experi ments with cyclodecanone dimethyl ketal and cyclodecanone methyl enol ether showed that both hydrolyze, under kinetic conditions, to yield at least 9 k , and. 93 • 83- cyclodecanone (Isolated as the semicarbazone). DISCUSSION OP RESULTS

THE KINETICS OP HYDROLYSIS OF HOMOLOGOUS CYCLANONE DIMETHYL KETALS

In the present Investigation the dimethyl ketals of cyclobutanone through cyclodecanone,* cyclododecanone,

•ft The rate constants of hydrolysis of cyclodecanone dimethyl ketal had to be determined in an indirect manner. This ketal could not be separated from the cyclodecanone methyl enol ether. Hence, both compounds were hydrolyzed competitively. The rate constants of the pure cyclodeca none enol ether were determined separately and the necessary corrections applied to the gross rate constant of the impure ketal to obtain the rate constant of "pure" cyclodecanone dimethyl ketal. Particulars are described in the experi mental section.

cyclotetradecanone, dl-n-propyl ketone, and di-n-hexyl ketone have been hydrolyzed in mixtures of 66.1% (by wt.)

1,2-dlmethoxyethane - 33 •?>% water. The temperatures of hydrolysis were between -2 1 .13° and +28.12°, and dilute hydrochloric acid was used as catalyst. The absolute and relative rates of hydrolysis of these cyclanone ketals, at various temperatures, are listed in Table 5; the corres ponding kinetic entropies, enthalpies, and free energies are summarized in Table 6.

The relative rates of hydrolysis of the cyclanone ketals are compared to those of homologous 1-chloro-l-methylcycloalkanes (26) and to acetolysis of secondary cyclanol

19 TABLE 5

Reaction Velocity Constants^ and Relative R a t e s ^ of Hydrolysis of Homologous Cyclanone Dimethyl Ketals in 66.7$ ("by wt.) 1,2-Dimethoxyethane - 33-3$ Water

D i m e t h v l ______Temperature. Relative Ketal of: 28.12^ 16.86 7.83 0.00 -10.69 -21.13 Rate

Cyclohutanone 2.88 ±0.03 0.459 +0.003^3) 0.1434 +V.0004 _ 0.0115 Cyclopentanone - 21? +2 95.8 ±1 .8^ ) 33.9 ±0 .3 10.7 Cyclohexanone 129.4 jp. 7 25.2 io.l'3) . 3,18 ±0.05 1.00

Cycloheptanone - - 471 *1°^. 174.4 ±1.2 41.6 ±1.0 9.64 ±0.15 54.9 Cyclo&ctanone - - 475 ±13' 158.7 ± 1 .3 36.8 ±1.2 7.48 ±0.03 ^9*9 Cyclononanone - 278.8 +5*^ 96.5 ±1.2 32.1 ±0 .5 - - 10.1

Cyclodecanone 653 £9 143-0 t l .8 - 16.43 to.24 - - 5.16 Cyclododecanone 5°*8 £0 .8 8.22 £o.21' 6) 2.39 ±0.03 - _ _ 0.205 Cyclotetra- decanone 54.8 to.8 9.14 to.13'6' 2.59 +0.03 - 0 .21?

Di-n-propyl- feetone - 136.2 tl.l 47-7 ±0.2 16.28 ±0.02 - - 5.12 Di-n-hexyl- ketone - - 2 .6l ± 0,0 3 - - 0.82

(1) k2 in l./m.-min.; deviations were calculated by adding the deviations from the average and dividing "by the number of runs (usually three). (2) Relative to cyclohexanone 1.00. All at 0°, or determined from rate constant at 0° which had been calculated from data at other temperatures. (3) Conducted at I5 .3 2 0. (4) Conducted at 8.42°. (5) Conducted at 7-93°. (6) Conducted at I5 .9 6 0. 21 TABLE 6

Activation Parameters for Acid-Catalyzed Hydrolysis of Homologous Cyclanone Dimethyl Ketals in 66.7% (hy wt.) 1,2-Dimethoxyethane - 33.3/^ Water

Dimethyl * Ketal of AH (KcaL/Mole) AS*(e.u. ) AF*(00KcaL/mole)

Cyclobutanone 24.7 17.5 19.9

Cyclopentanone 17.9 6.0 16.3 Cyclohexanone 21.0 12.5 17.6 Cycloheptanone 18.3 10.8 15.4

Cyclooctanone 19.5 15.2 15.4

Cyclononanone 20.8 16.6 16.3 Cyclodecanone 21.2 16.5 16.7 Cyclododecanone 24.9 23.8 18.4

Cyclotetradecanone 2*+. 8 23.7 18.4

©i-n-propyl ketone 20.4 13.6 16.7 22 tosylates (24) (all unimolecular dissociation processes in the rate-determining step of the reaction) in Figure la, b, and c. In general the effects of ring size on the reactivity of these systems are similar. Belative to the rates of the six-membered ring, the four-membered ring reacts slowly and the five- and seven-membered ones very rapidly. A maximum in the relative rates, depending upon the individual reaction, takes place between the seven- and ten-membered rings. The rate constants for reactions of the higher-membered rings drop off rapidly.

The ordering of the relative rates for the three reactions being compared are:

Cyclanone ketal hydrolysis 7 > 8 > 9 — 5>10> 6>12? 14> 4;

Cyclanol tosylate hydrolysis 10> 8 — 9> H > 7> 5>12>13 >15 > 14> 6;

1-Chloro-l-methylcycloalkane hydrolysis 8 >5 — 7> 9> 10 >11 > 13 > 1 5 > 6> 4.

The seven-, eight-, and nine-membered rings always react relatively rapidly, whereas the six-membered ones react relatively slowly. The four- through seven-membered rings show similar patterns:

Cyclanone ketal hydrolysis 7> 5> 6> 4

Cyclanol tosylate hydrolysis 7 >5>6 f- l-Chloro-^nethylcycloalkane hydrolysis 7 — 5> 6> ** 23

B -10

8 -

8 - 5 - A

-8 -9

7- -10 5 -D -9

-10

12- -13 -15

14- -6 -6 -6

-14 12-

A. Hydrolysis of Cyclanone Dimethyl Ketals, 0°, 66.7% Dimethoxyethane, 33.3% Water B. Acetolysis of Cyclanol Tosylates, 70°, Glacial Acetic Acid C. Hydrolysjs of I - Methyl-1-Chloro Cyclo- alkanes, 25°, 80% Ethanol (Numbers on plots indicate carbon atoms in ring)

Figure 1« Relative Rates of Reactions 2k

In general the relative rates of hydrolysis of these ketals follow closely the I-strain theory (3D» I-strain

(31) H. C. Brown, E. S. Fletcher, and R. B. Johan- nesen, J. Am. Chem. Soc., 22., 212 (1951).

has "been defined as the sum of the internal strains arising in a ring system from bond opposition forces, angle distor tions, and compression of van der Waal's radii. Each factor may have different importance in rings of various sizes.

At present there is no satisfactory quantitative method for independently evaluating each of these factors.

In the small rings (three- and four-membered) bond angle distortions are probably the major sources of strain.

In the common rings (five-, six-, and seven-membered) forces arising from bond oppositions appear to serve as the major sources of strain. In the medium-sized rings (eight- through twelve-membered) combinations of compression of the van der Waal's radii and bond opposition forces make up the

Internal strain. Large rings (thirteen-membered and up) are relatively free of these strains; they are so large and flex ible that they approximate open-chained compounds.

If cyclobutane rings are square-planar, then the carbon-carbon bond angles must be distorted by 19.5° from the normal 109.5° of a carbon atom which Is sp^ hybridized. 25 2 The preferred angle of a sp hybridized carbon atom is

120°; since the angle in such a four-membered ring will be

approximately 90°, a distortion of 30° will be involved.

If the transition state in the rate-determining step of the reaction, in which the coordination number on carbon changes from four to three, approximates a trigonal carbon atom, then an angle change of 10.5° is involved. Such a change is resisted, hence the rate of the reaction will be slow in four-membered rings (cyclobutanone dimethyl ketal 0 .0115) in comparison with that of open-chained analogs (di-n-hexyl ketone dimethyl ketal 0.82; cyclohexanone dimethyl ketal * 1.00). Because of the considerable increase in the I-strain

It has been found (32,33) (hydrolysis of lactones and neutralization of nltro compounds), that the four- membered ring exhibited anomalously lower and higher reac tivity, respectively, than would be expected on the basis of the above argument. It is of interest that the results of the present study are in substantial accord with the I-strain concept as regards the relative reactivity of the four-membered ring.

(32) C. A. Matuszak, Ph.D. dissertation, The Ohio State University, 1957* p. 69. (33) P* W. K. Flanagan, Ph.D. dissertation, The Ohio State University, 1957* p. ^2. between the ground state and the rate-determining transition state in a four-membered ring compound, a corresponding increase in the kinetic enthalpy would be expected. The 26

hydrolysis of the cyclobutanone dimethyl ketal shows a

much larger kinetic enthalpy (2k. 7 Kcsl./mole) than the

six-membered dimethyl ketal (21.0 Kcal./mole).*

•ft Professor S. M. McElvain communicated privately that cyclopropanone diethyl ketal is soluble in cold, con centrated hydrochloric acid and can be recovered after standing for JO minutes by dilution of the solution with water. This indicates the very considerable stability of this ketal under conditions tinder which all of the ketals studied would have been hydrolyzed instantly.

The shape and conformations of the saturated five- membered ring have not been established with certainty. The ring system is usually idealized as planar, and the strain . involved is assumed to arise from interactions of adjacent hydrogen atoms and not from distorted bond angles. A planar structure for the five-membered ring may not be quite cor rect (3*0 ; however, the actual structure of the saturated

(3*0 W. G. Dauben and K. S. Pltzer, "Conformational Analysis," Chapter 1, p. 35; of M. S. Newman, "Steric Effects in Organic Chemistry," John Wiley and Sons, Inc., New York, N. Y., 1956.

ring does not affect generad I-strain predictions. In a saturated, planar five-membered ring the hydrogen atoms are assumed to be in the high-energy eclipsed conformation(3 5)*

(35) Reference Jk, p. 5 27 In cyclopentane there are ten such hydrogen Interactions.

If a reaction is carried out in which the ground state te

tragonal carbon atom changes to a trigonal one in the rate-

determining step of the reaction, then four of the ten bond

oppositions are removed. This should result in a larger

reaction rate of a five-membered ring relative to the four-

and six-membered homologs. In the present investigation,

the facts that the relative rates of reaction of cyclopentanone dimethyl ketal, cyclohexanone dimethyl ketal, and

cyclobutanone dimethyl ketal are 10.7 : 1.00 ; 0.0115 are

In agreement with the general theory of strain in five-membered rings. The ordering of the kinetic enthalpies for four-, five- and six-membered ketals (24.7, 17*9> 21.0 Kcal/ mole) are predicted by the I-strain theory.*

* In a five-membered ring, an angle strain of 10.5° is imposed when the coordination number on carbon changes from four to three in the rate-determining step of the reaction. For saturated rings larger than the four-membered one there appears to be no serious angle distortion due to the ring size. When the ring size is increased the molecule can more readily accommodate the extra strain.

Models of cycloheptanone dimethyl ketal indicate that bond oppositions exist which may be responsible for the high relative rate of hydrolysis. The models also show that an axial methoxyl oxygen interacts with two axial hydrogens in 28 the 3- &E-3. 5-Positions. Such trans&nnular interactions

should act as additional driving forces, assuming that the

trigonal transition state has less interaction of either

the bond opposition or transannular Interaction kind.

Cycloheptanone dimethyl ketal (54.7) reacts even

faster than the cyelopentanone dimethyl ketal (10.7), and

its reaction rate is much greater than that of cyclohexa

none dimethyl ketal (1.00). The kinetic enthalpy for the

hydrolysis of cycloheptanone dimethyl ketal (18.3 Kcal./ mole) is only slightly larger than that for cyelopentanone

dimethyl ketal (17.9 Kcal./mole) and smaller than the one for cyclohexanone dimethyl ketal (21.0 Kcal./mole).

The relative unr.eactivity of the cyclohexanone di methyl ketal is related to the conformation of cyclohexane rings. These prefer a chair conformation (36) in which all

(36) 0. Hassel and H. Virvoll, Acta Chem. Scand., 1, 149 (1947). vicinal hydrogens are staggered and thus do not interact appreciably. These rings are very flexible, unstrained and much like an open-chained analog. Replacement of a tetrag onal carbon atom in the ground state of the cyclohexanone dimethyl ketal by a trigonal one in the transition state of the rate-determining step leads to a partial loss of the 29 staggered arrangement, to partial bond oppositions and to angle strain (minor) relative to an open-chaln analog.

Reactions which involve a change in the coordination num ber on carbon from four to three are thus resisted. This interpretation is not quite in accord with the experimental facts when a comparison is made with an open-chained ketal

(cyclohexanone dimethyl ketal 1.00, dl-n-hexyl ketone di methyl kets-l 0 .82), however other factors such as solva tion, entropy effects, etc., may change the reactivity of the di-n-hexyl ketone.

In six-membered and higher ring ketals it is pos sible to protonate an axial or an equatorial methoxyl group. The subsequent step will involve loss of an alco hol molecule from either position. Models indicate that protonation of the equatorial alkoxide would lead to a less hindered molecule than protonation of an axial alkox ide. But the loss of an axial protonated alkoxide, as an alcohol molecule, may be favored since this removes a group In an energetically less favorable position. The equatorial and axial protonated ketals may well be react ing competitively. It is Interesting but futile to specu late in connection with this matter; any experimental solution seems remote.

The medium-sized rings (eight- through eleven- membered) cannot be analyzed in such a relatively simple manner. These larger rings are probably much less rigid than the common ones and such a condition could lead to considerable freedom of motion of the atoms In the molecule. 30

Prelog (37) has made an analysis of the conformation of

(37) V. Prelog, "Bedeutung der vielglledrlngen Bingverbindungen f&r die theoretische organische Chemie," Chapter 5, P. 103; in Sir Alexander Todd, "Perspectives in Organic Chemistry," Interscience Publishers, Inc*, New York, N. Y., 1956.

cyclodecane. Figure 2 represents a sketch of cyclodecane as constructed by Hlrshfelder models. This particular model has no eclipsing hydrogens, a minimum of transaimu- lar interaction and the strain is fairly evenly distributed throughout the molecule. This structure should be consid ered as a dynamic one in which the atoms are constantly changing their relative positions. The strain in this molecule arises from two sources, the repulsion of adjacent equatorial hydrogens and the transannular interaction of the axial hydrogens in the 1,3 and 1,5 positions. Examination of Figure 2(a) indicates that replace ment of a hydrogen by a more bulky group should lead to the less hindered equatorial isomer. The replacement of a te tragonal carbon atom by a trigonal one leads to a lessening of the 1,2, 1,3, 1,5 interactions in the ring. The decrease in strain is greatest when the trigonal carbon Is in the position indicated by Figure 2(c), that is on the long side of this pseudo-elliptical molecule, since more oppositions 31

(a) Cyclodecane

(b) Cyclodecane cation

Figure 2 * Conformations of Cyclodecane (a) and Cyclodecane Cation (b,c) (9). 32 are removed than are in the cation of Figure 2(b). It is possible to arrive at similar conclusions concerning the other rings in the medium-sized series. The molecules con taining an odd number of carbon atoms must have at least one pair of adjacent hydrogens which are in eclipsed posi tions.

When the number of carbon atoms in the medium- sized series is raised from eight to eleven the resulting molecules become less strained. There should be less inter action in both the ground state as well as the transition state in the larger members of this series, and, therefore, an Increase in ring size should be accompanied by a decrease in the reaction rates. This theory is In line with the experimentally determined rates of ketal hydrolysis (8> 9>

1Q> 6); In addition the kinetic enthalpy increases with increase in the number of carbon atoms in the ring (Table 6).

The ketals of the large rings (twelve-membered and up) have rates which are similar to those of open-chained ketals. Thus cyclododecanone dimethyl ketal has a rate, relative to cyclohexanone dimethyl ketal (1.00), of 0.20, cyclotetradecanone dimethyl ketal 0.21, and di-n-hexyl ke tone dimethyl ketal 0.82. Both the kinetic enthalpy

(excepting the four-membered ring) and the entropy are much larger than those of any other ketals in this series (Table

6). A similar increase was noted in the activation parameters of the tosylate acetolysis (Table 7).

These larger ring ketals (twelve- and fourteen- membered) are apparently not subject to such strains as the medium-sized ones are. The twelve-membered and larger rings (38,39) do not undergo transannular reactions as do

(38) V. Prelog and V. Boarland, Helv. Chlm. Acta, 1 8, 1776 (1955). (39) V. Prelog and M. Speck, Helv. Chlm. Acta, 18, 1786 (1955). the medium-sized homologs (seven- to eleven-membered).

There appears to be little or no van der Waal's compression in the twelve- or higher membered rings which might be the cause of the transannular reactions. Models show that the twelve- and fourteen-membered rings can exist without eclipsed hydrogens*

THE EFFECT OF THE ALCOHOL GROUiS ON THE RATES OF HYDROLYSIS OF CYCLOBUTANONE, CYCLOPENTANONE, AND CYCLOHEXANONE DIALKYL KETALS The absolute rate constants of hydrolysis of dimethyl, diethyl, and diisopropyl ketals of cyclobutanone, cyclopentanone, and cyclohexanone at different temperatures are compiled in Table 8. The relative rates at 0° and the kinetic enthalpies and entropies are listed in Table 9. 34

TABLE 7

Activation Parameters of the Hydrolysis of Cyclanol Dimethyl Ketals and the Acetolysis of Cyclanol Tosylates (24) Ketal Tosylate “7“ Number of Carbon — ^flrP.lXpls ^c£to|ys i g>3,1— Atoms in Ring A H ^ D AS^ (2 ) A # u > A S ^ 2 '

4 24.7 17.5 - - 5 17.9 6. o 24.1 -4.2

6 21.0 12.5 27.3 -0.5

7 18.3 10.8 23.3 -5.7

8 19.5 15.2 22.3 -4.5 9 20.2 16.6 22.5 -4.2

10 21, 2 16.5 23.0^4) -l.l(4)

11 - - 23.7 -3.2

12 24.9 23.8 27.6 +2.8

13 -- 26.2 -1.3 t\> •{r 00 14 « 23.7 27.8 +1.7

15 -- 26.5 -1.3

(1) Kcal./mole

(2) e.u.

(3) Reference (24) (4) Reference (25) TABLE 8

Bates of Hydrolysis of Dialkyl Ketals of Cyclohutanone, Cyelopentanone and Cyclohexanone(1)

Temperature Bate Constants k% Tl~./m.«»mih.7 Comnound ^2 1 .1 3 -1 0 .6a. 0.00 7.83 15.86 28.12

Cyclolratanone dimethyl ketal ** 0.1434 ±0.004 0.459 +0.003^ 2.88 iSD.03 Cyclohutanone diethyl ketal •m — 0.594 to.013 1.825 ±0.012?^ 10.67 to.17 Cyclohutanone diisopropyl ketal 9.26 ±0.15 73-9 to.3 292 +1

Cyelopentanone dimethyl ketal 33.9 ±0.3 95.8 ^L.8(3) 21? 12 Cyelopentanone diethyl ketal 21.8 +0.2 87.3 ±0 .3 226.3 t 3 — — Cyelopentanone diisopropyl ketal 12k.7 ±1.? 442 +8 1534 +20 Cyclohexanone ^dimethyl ketal ■** “ 3-18 +0.05 *• 25.2 + 0 .1^dimethyl 129.4+3.7 Cyclohexanone diethyl ketal 9.25 +0.7 30.8 +0.4 93-^12.0 — Cyclohexanone diisopropyl ketal 22.6 +0.6 111.7 +.1.5 48512 - - -

(1) In 66.7$ (ty wt.) 1,2-dimethoxyethane - 33*3/® water. (2) I5 .320 reaction temperature. (3) 8.43° reaction temperature. TABLE 9

Relative Bates and Activation Parameters for Hydrolysis of Dimethyl, Diethyl, and Diisopropyl Ketals of Cyclobutanone, Cyelopentanone, and Cyclohexanone^)

Compound Relative Rate (0°)

Cyclobutanone dimethyl ketal 0 .0115*2) 2^.7 17.5 Cyclobutanone diethyl ketal 0 .0500'2) 23.7 16.8 Cyclobutanone diisopropyl ketal 2.91 19.3 8.5

Cyelopentanone dimethyl ketal 10.? 17.9 6.0 Cyelopentanone diethyl ketal 27.5 18.1 8.6 Cyelopentanone diisopropyl ketal 1+82 15.7 5.5

Cyclohexanone dimethyl ketal (1.00) 21.0 12.5 Cyclohexanone diethyl ketal 2.91 22.1+5 20.1 Cyclohexanone diisopropyl ketal 153 19.3 16.3

(1) In 66.7$ (by wt.) 1,2-dlmethoxyethane - 33*3$ water.

(2) Calculated from rate constants at higher temperatures.

(3) Kcal./mole.

(4) e.u.

On 37 Table 10 Illustrates how the relative rate of the cycla

none diethyl and dllsopropyl ketal varies with respect to each corresponding cyclanone dimethyl ketal.

In general the rates of reaction of these ketals increase upon substitution of ethyl and lsopropyl radicals

for methyl on the alcohol group of the ketals. Several

factors could produce such changes:

1) Relief of B-strain

2) Effects of the leaving group

3) Promotion of protonation due to inductive effects of the alkyl groups.

In the discussion of the "Mechanism of Ketal Hydroly

sis" It was concluded that there is probably no, or at least

minimal, steric hindrance to protonation of the homologous

cyclanone dimethyl ketals. If steric hindrance to protona

tion had been a major factor in the hydrolysis of the ethyl and lsopropyl ketals then the rates of hydrolysis would probably not have increased much, or they may even have decreased. Hence steric hindrance to protonation cannot be a major factor in the hydrolysis of these ethyl and lsopropyl ketals.

B-strain (40) occurs In compounds in which highly

(40) H. C. Brown and M. Nakawaga, J. Am. Chem. Soc., ZZ, 3610 (1955). 38

TABLE 10

Relative Rates of Hydrolysis of Dialkyl Ketals of Cyclanones and Formaldehyde (0°)

Cyclo Cyclo- Cyclo Formal^ Ketone butanone pentanone hexanone dehvde’

Dimethyl 1 1 1 1

Diethyl 4.35(D 2.57 2.91 8.5

Diisopropyl 253 45.0 153 47.2

* Reference (18).

(1) Calculated from rate constants at higher tem peratures.

branched groups are in the neighborhood of the reacting center. In the hydrolysis of open-chained acetals and ketals (see "The Mechanism of Hydrolysis of Acetals and

Ketals," also Reference 21) the diethyl ketal of 3-methylbutanal ("six-number" of six) hydrolyzed at a rate predicted by the polar substituent constants for hydrogen and the isobutyl radical, while the diethyl ketal of 3*3-3-1- methylbutanal ("six-number" of nine) hydrolyzes approxi mately twenty times as fast as predicted by the polar sub stituent constants for hydrogen and the neopentyl group.

The "six-number" of the alkyl groups of the alcohol portion of the molecules in this study never exceeds zero, while 39 the "six-number11 of the cyclanone portion cannot be larger

than four. On this basis it may well be that there is no

appreciable B-strain involved in the rates of hydrolysis

of these ketals.

In comparing the relative rates of the dialkyl for-

mals (methyl ketal rates = 1.00, Table 10) with those of

the corresponding dialkyl cyclanone ketals, it is seen that

the relative rate of each cyclanone ketal is roughly the same (within a factor of five) as that of the corresponding

formal. This should rule out B-strain as a major factor which changes the rates of hydrolysis of these dialkyl ketals.

A change in the alkoxy group also represents a change in the nature of the leaving group. lsopropyl alco hol should be a poorer leaving group, e.g., slow down the reaction if this were a controlling effect, than a methyl ■ * alcohol molecule. Since the rates of reaction of these

The isopropyl alcohol oxygen should be less elec tronegative than the methyl alcohol oxygen (due to the electron donating capacity of the extra methyl groups)* Since the transition state represents at least an incip ient separation of an increasing positive charge (the carbonium ion to-be) from a roughly neutral one (the alco hol molecule) the electronegativity of the alcohol oxygen could be the controlling factor of the nature of the leav ing group* Since the isopropoxide oxygen is less electro negative it will be separated less readily from the incipient carbonium ion than will the methyl alcohol. Hence, isopropyl alcohol may be a poorer leaving group than methyl alcohol. 40

ketals increase when a methyl group is replaced hy an iso-

propyl group, the leaving group effect cannot be controlling.

The replacement of hydrogen by methyl groups, on the

methoxide radical, should favor protonation of the alkoxide

oxygen, since the additional methyl groups are electron

releasing. Hence, a shift in the ketal-protonated ketal

equilibrium is expected to take place towards the proton ated side. A higher concentration of protonated species will tend to step up the over-all reaction rate.

If differences in the degree of protonation are the only factors which produced these large changes in the rates of hydrolysis of dialkyl ketals, then it would be expected that the relative rates of hydrolysis of the four isopropyl and ethyl ketals would be the same (Table 10). This is not quite so. For example, the ratio of the relative rates of the diisopropyl formal and the cyclobutanone diisopropyl ketal is 1:5.* Diisopropyl formal and cyclohexanone

This large ratio may indicate that there is a certain amount of methoxyl-hydrogen eclipsing Interaction In the four-membered ring.

diisopropyl ketal also have a larger relative rate ratio

(1:3)» while the ratio of the diisopropyl formal and the corresponding five-membered ring ketal is 1:1. This should 41

Indicate that there is another factor involved, but one

of only minor nature. It is of interest to note that the

ratio of the relative rates (with constant alcohol groups)

increases from Cij'x Cg < Cjj,. This sequence is the inverse of

the relative rates of reactions predicted by I-strain theory

on the four-, five-, and six-membered rings in which the

coordination number changes from four to three in the rate-

determining step of the reaction.

The kinetic entropy and enthalpy values reveal lit-

tie beyond the fact that AH for reaction of the three

isopropyl derivatives is always smaller than that for the

diethyl and dimethyl ketals of the corresponding ketones.

With the exception of the six-membered ring this also holds

for the AS terms. No other correlation seems to exist in

this series.

The relative stabilities of four-, five-, and six- membered cyclanone hemiketals of ethanol and methanol (41)

(41) 0. H. Wheeler, J. Am. Chem. Soc., £2.* **191 (1957). are shown in Table 11. These data show qualitatively the

same general trend as do the rates of hydrolysis of the dimethyl and diethyl cyclanone ketals (Table 10). The equilibria are pushed further towards the ketone plus TABLE 11

Hemiketal Equilibrium Constants of Cyelanones with Methanol and Ethanol (41)

K*(MeOH) K*(EtOH) K(EtOH) K(MeOH)

Cyclobutanone 1.11 327 294

Cyelopentanone 15 • 1 810 53.5

Cyclohexanone 2.16 237 110

(Alcohol] [Ketone] . 25° (Hemiketal}

alcohol side when ethyl alcohol is used in place of methyl alcohol. The rate of the hydrolysis reaction is increased when a diethyl ketal is used in place of the corresponding dimethyl ketal. The equilibria are again much more sensi tive to structured changes than are the kinetics.

In summary, the Increase in the relative rates of ketal hydrolysis, on varying the alcohol portion of the molecule from methyl to ethyl and to isopropyl, might be attributed largely to an increase in the concentration of protonated ketal in the equilibrium reaction preceding the rate-determining step of the hydrolysis. Steric hindrance to protonation or relief of B-strain do not appear to be a major factor in these reaction rates. When methyl groups, on the alcohol portion of the molecule, are replaced by ^3 ethyl and lsopropyl groups, the order of the relative rates of hydrolysis of the ketals Is maintained: five-membered faster than six-membered, faster than four-membered.

THE EFFECT OF ALKYL GROUPS ON THE RATES OF HYDROLYSIS OF METHYL RING- SUBSTITUTED CYCLOBUTANONE, CYGLOPENTANONE, AND CYCLOHEXANONE DIMETHYL KETALS

The hydrolysis rates of methyl ring-substituted cyclanone dimethyl ketals have been determined in order to test current theories of kinetic reactivity of cyclic com pounds, and also to gather additional data on the reactivi ties of substituted cyclic rings.

The absolute rates of hydrolysis of the methyl ring- substituted dimethyl ketals of the present investigation, at various temperatures, are listed in Table 12. The kinet ic enthalpies, entropies, and free energies of these reac tions are summarized In Table 13. The relative rates of hydrolysis of these ketals are compared in Table 16.

There have been only a few investigations of the effects of substituents on the kinetics of reaction of cyclic compounds. Harper (42) determined the rates of

(42) R. H. Harper, Ph.D. dissertation, The Ohio State University, 1957> PP- 125-126* hydrolysis of the 1,3-dioxolanes and 1 ,3-

14). TABLE 12

;!Rate Constants of Hydrolysis of Methyl-substituted Cyclanone Dimethyl Ketals in 66.7^ (by wt.) lj2-Dimethoxyethane - 33-3$ WaterU)

Temperature t 0 0.00 2,83, 15.66 28.12

Dimethyl ketal ofi

Cyclobutanone 0.1434 i0.0004 0.459 to.003^ 2.88 to.03 2,2 ,4,4-Tetramethyl- cyclobutanone 0.01515 to.0005 - 0 .1?77t0 .0005 0.986 to.004

Cyclopentanone 33.9 to.03 95-8 tl.8(3) 217 t2 2-Methylcyclo- pentanone 53.6 to.2 135.5 t l .5 325 ±9 3 ,3-Dimethyl- cyclopentanone 9.83 to.11 26.2 to.l 66.5 ±0.9 -

Cyclohexanone 3.18 to.05 25.2t0.1^2) 129.4 +3.7 2-Methylcyclo- hexanone 10.59 t0.11 35.7 to.5 99.5+1.0 3 »3~I>tillethylcyclo- . hexa.no ne 5.69 to.19 270 t7 3 * 3 »5 > 5 ~Tetramethyl- cyclohexanone 10.-Wt0.30 - 101.4 +0.9 531 t4

(1) Rate constants in l./m.-min. The deviations were calculated by adding the deviations from the average rate constant and dividing by their number (usually three). (2) Conducted at I5 .320. (3) Conducted at 8.43°. 45 TABLE 13

Relative Rates of Hydrolysis and Kinetic Parameters of Methyl-substituted Cyclanone Dimethyl Ketals

Relative AF* <1 > Dimethyl Ketal of Rate (0°) a s *<2 > ion.. Cyclobutanone 0.0115^3) 24.7 17.5 19.9 2,2,4,4-Tetramethyl- cyclobutanone 0.004?7 23.8 12.4 20.45

Cyclopentanone 10.7 17.9 6.0 16.3 2-Methylcyclopentanone 16.9 17.2 ^•5 16.0 3 ,3-Dimethylcyclo- pentanone 3.09 18.4 5.25 16.9

Cyclohexanone (1.00) 21.0 12.5 17.6 2-Methylcyclohexanone 3.32 21.9 18.5 16.9 3 ,3-Dimethylcyclo- hexanone 1.79 21.6 16.0 17.2 3 »3 »5,5-1’etramethylcyclo hexanone 3.29 22.3 19 * 6 16.9

(1) Kcal./mole

(2) e.u.

(3 ) Extrapolated from results obtained at higher temperatures. 46

TABLE 14

Relative Rates of Hydrolysis of Cyclic Ketals (42)*

Cyclo Cyclo- 2-Methy1- Ketone hexanone pentanone cyclopentanone Ketal l,3-<3.1oxolane (1.00) 13.0 8.02 1,3-dloxane 3 0 .6(1 .00) 172(5.62) 259(8.43)

* In 70:30 (by vol.) dioxane-water, 3°°.

Others (31) have Investigated the rates of hydroly sis of 1-chloro-l-methylcyclohexanes which have methyl substituents in the 2, 3> 4 positions (Table 15).

TABLE 15 Relative Rates of Hydrolysis of Methyl-Substituted 1-Chloro-l-Methylcyclohexanes (3 1 )*

Compound Relative Rate

1-chloro-l-methylcyclohexane (1.00) 1-chloro-l,2-dimethylcyclohexane 0.75 l-ehloro-l,3-<3.1iaethylcyclohexane 0.81 1-chloro-l,4-dimethylcyclohexane 1.27

In 8 0 $ (by vol.) ethanol, 25°.

The rates of saponification of simple and methyl- substituted lactones have recently been determined (43* (4-3) T. J. Dougherty, unpublished results.

Table 17). Hydrolysis of lactones differs from that of ketals and 1-chloro-l-methylcycloalkanes in that the reaction

Is blmolecular and the coordination number changes from three to four in the rate-determining step (addition of hydroxide ion to the carbonyl group).

TABLE 16

Relative Rates of Hydrolysis of Methyl-substituted Cyclanone Dimethyl Ketals

Dimethyl Ketal of Relative Rate (o°) Cyc1obutanone (l.oo)t1 ) 2,2,4,4-Tetramethybyclobutanone 0.415 Cy clopent anone (1.00) 2-Methylcyclopentanone 1.58 3,3-Dlmethylcyclopentanone 0.289

Cyclohexanone (1.00) 2-Methylcyclohexanone 3.32 3 ,3-Dimethylcyclohexanone 1.79 3 >3 >5,5-Tetramethylcyclohexanone 3.29

(1) Extrapolated from results obtained at higher temperatures.

The thermodynamic properties of reactions of cer tain substituted ketones have been investigated (41,44,45).

(44) 0. H. Wheeler and J. Z. Zabicky, Chem. and Ind., 1388 (1956). 48

TABLE 17

Relative Rates of Saponification of Lactones (43)*

Lactone Relative Rate (0°)

Proplolactone 0.0568 a-Methylpropiolactone 0.0560 p , P-Dlraethy'lpropiolactone 0.00320 Butyrolactone 0.0285 (1 .00 ) a-Methylbutyrolactone 0.0150 0.520 Valerolactone (1.00) a-Methylvalerolactone 0.445

* 5 0 :50 (by vol. ) 1, 2-dimethoxyethane-water.

(45) 0. H. Wheeler and J. Z. Zablcky, Can. J. Chem., 26, 656 (1958).

The equilibrium constants for reaction of cyclanones with hydrogen cyanide (Table 18), and with methyl and ethyl alcohols (Table 19) have been determined. These are the best and most extensive data of this kind. A large number

Of investigators (45) have carried out similar work but

exclusively with open-chained or unsubstituted cyclic ketones. A large number of open-chained diethyl ketals, in which the alkyl groups on the ketone portion of the mole

cule have been varied, have been hydrolyzed (16, Table 20). 49 TABLE 18

Absolute and Relative Equilibrium Constants for Reaction of Ketone and Hydrogen Cyanide (44)*

[ncg [,c— o} Relative K 2-5= Equilibrium Ketone Used D Constant [>~CNjNj T Cyclohexanone 5.91 (1 .00) 2-Methylcyclohexanone 10.7 1.8 3-Methylcyclohexanone 5.5 0.93 4-Methylcyclohexanone 3.15 0.53 2 ,2-Dimethylcyclohexanone 9.2 1.6 Cls-3,5-Dlmethylc.yclohexanone 25.7 4.4 3 ,3-Dimethylcyclohexanone 176 30 3 ,5-Trlmethylcyclohexanone 224 38 3 »3 >5,5-Tetramethylcyclohexanone 4690 800

* 95^ ethanol, 25°.

In comparing the kinetic data of the present in vestigation (Tables 13* 14, 15» 16, and 17» with the thermodynamic equilibrium data (Tables 18 and 19) it be comes clear that: 1 ) thermodynamic effects in these reactions are much more sensitive to substitution on the ring than are the corresponding kinetic effects,

2 ) there is no quantitative free energy relation ship between the kinetic and thermodynamic results,

3 ) substitution of a methyl group in the two posi tions on five- and six-membered rings does not change the 50 TABLE 19

Absolute and Relative Equilibrium Constants for the Ketone-Alcohol-Hemiketal Equilibria (41)

.25- & H ?0 H l f > 6] „ g < tC2H SOH3[>=°) d r ■d r v 0H I Relative L r \ o c h 3J 1 / ' o c 2h 5 J Relative Ketone Equillb- Equilib- Used riuin rium

# In absolute methanol or ethanol, 25°.

TABLE 20

Rates of Hydrolysis of Open-Chained Diethyl Ketals and Acetals(1°)*

0 u Absolute Rate Relative B x - C - R 2 ll./nv-sec.) Rate

E 1 r 2 H H 4.13 x 10-5 1.67 x lO"^ ch3 H 0.248 (1 .00) CHoCH2 H 0.267 1.08 (CHo)2CH H 0.164 0.66 (CHo)q C H 0.188 0.76 (CH3 )2CH C ^ H 0.167 0 .6? CH*a CHo 75 2 3,040 CH3 CH2 CH3 720 2,910 neo-C^H^q CH3 9,200 37,100

* In 50:50 (by vol.) dioxane - water, 25^. 51 equilibria (Tables 18, 19) nor the kinetic values (Tables l^j 15> 16» 17) much, relative to the unsubstituted cyclanones,

4) relative to the activation parameters of the unsubstituted ketals, methyl substituents on five- and six-membered rings do not produce large changes in the

AH* or AS^ values (Table 13).

There is evidence (3*0 which suggests that the five- membered ring is not planar. One of the five carbon atoms lies out of the plane which the other four form. Each of the five carbon atoms alternates in this out-of-plane mo tion. How ring substitution influences this is not known, but the replacement of a sp^ hybridized carbon atom in the o ring by a sp^ hybridized carbon atom must introduce an ele ment of rigidity into the ring which it formerly did not o possess. The introduction of a sp hybridized carbon atom into the ring will also serve to increase the Interference between the eclipsed hydrogen atoms in the ring, because at least some opportunities for relief of strain (staggered hydrogens) have been removed. In addition, the substitution of a 120° angle for a 109° angle in the five-membered ring, might, if the atoms were all in a plane, force both sp3 p hybridized carbon atoms next to the sp hybridized atom further apart and thereby cause more interference between the eclipsed hydrogens on the carbon atoms in the three 52 and four positions of this five-membered ring. Such

subtle conformational effects may not be detectable experi

mentally in the unsubstituted five-membered ring.

It might be expected that in the fIve-membered ring

the ratio of the rate of reaction of the 2-methyl ketal to

the unsubstituted ketal would be larger than the ratio for

the corresponding six-membered ring ketals. The rate-

determining step of the reaction (loss of a molecule of

methyl alcohol) would appear to relieve more strain in the

five-membered ring substituted in the two position than in

the six-membered ring substituted in the two position.

While this factor provides for the gross difference in the

absolute reaction rates between the five- and six-membered

rings, it does not account for the smaller ratio of the

rate of reaction of the 2-methylcyclopentanone ketal to

cyclopentanone ketal (1.58), compared with the respective

ratio of the six-membered ring pair (3 -3 2 ).

In order to account for the difference of the pre vious discussion, more subtle conformational relationships

and angle strain energies must be considered. It is per haps to be expected that in the transition states (near to product) of 2-methyl five- and six-membered carbonium ion

intermediates, the hydrogen-methyl group interactions in the five-membered ring must be much larger than in the 53 corresponding six-membered one. The methyl group in the

corresponding six-membered ring transition state will be

in the uneclipsed equatorial position, unencumbered by

adjacent hydrogens, while the methyl group in the five-

membered ring is pressed back against the eclipsed hydro

gens of the three position, which in turn eclipse the

hydrogens in the four position. The increase in interfer

ence of these eclipsed groups may be due to broadening of p the angle of the sp hybridized carbonium ion. Such inter

ference will tend to slow the rate of reaction more in

rigid, substituted five-membered ring ketals than in the

relatively strain-free six-membered analog.*

This concept involving alkyl group - hydrogen crowding is similar to that of Wheeler (41, 4.5) in his dis cussion of "equatorial interference" in six-membered rings.

If the steric requirement of the Interfering group in

the three or four position of the five-membered ring ketal were increased, the ratio of the rate constants of the sub

stituted ketal to unsubstituted ketal would be expected to

decrease because of the extra energy required to accommodate

the transition state. The experimental results of this

study are in agreement with the argument presented. Place ment of the gem-dimethyl group in the three position of 54 cyclopentanone dimethyl ketal yields a molecule whose hydrolysis rate, relative to the unsubstituted ketal, is less than one-third (0.29) as fast. The compressive strain in the transition state leading to the carbonium ion is so large that it minimizes the tendency of the five-membered ring ketal to go to a configuration which has fewer inter ferences due to eclipsed groups.*

The absolute rate of hydrolysis of the cyclopentanone dimethyl ketal is (l./m.-min., 0°) 33*9 snd of the 3>3- dimethylcyclopentanone dimethyl ketal is 9.83. Extrapolat ing the above theory and these results, it is predicted that the 3 »3»4,4-tetramethylcyclopentanone dimethyl ketal will hydrolyze at a rate comparable to or less than that of cyclohexanone dimethyl ketal (3-18).

If there is a larger degree of compressive strain in the transition state of the substituted than in the unsub stituted cyclopentanone dimethyl ketal, then it might be J- expected that an Increase in the AHT 's for the substituted five-membered ketals would take place, provided no other factors, such as solvation, etc. were involved. It was found contrariwise that the AH for hydrolysis of the

2-methylcyclopentanone dimethyl ketal is somewhat smaller

(Table 13* 1?.2 Kcal./mole) than that for the unsubsti tuted dimethyl ketal (1?.9 Kcal./mole) but the 3 »3-<3.imethyl- cyclopentanone dimethyl ketal shows the expected gain

(18.4 Kcal./mole). 55 2,2,4,4-TetramethyIcyclobutanone dimethyl ketal hydrolyzes, unexpectedly, less than half as fast as the

unsubstituted analog (0.42:1, Table 16). The slow rate

of the 2,2,4,4-tetramethylcyclobutanone dimethyl ketal was unexpected; it was thought that methyl-methoxyl eclips

ing interactions would accelerate the reaction consider ably. There are many reasons which may account for this change in rate upon introducing 2,2,4,4-tetrsmethyl substit uents. Beplacement of four alpha hydrogens in cyclobutanone dimethyl ketal by methyl groups removes four C-H hyperconjugation possibilities.* This should slow down the

# The evidence as to the effectiveness of C-H as compared to C-C hyperconjugation stabilization of carbonium ion transition states is conflicting. Taft (21) points out that, in the hydrolysis of open-chained diethyl ketals, on substitution of methyl groups for alpha hydrogens the rates of hydrolysis of ketals decrease below those expected on the basis of£(r* correlation values. The decrease in C-H hyperconjugation was treated as a linear function of the number of alpha hydrogens; C-C hyperconjugation did not have to be included to obtain satisfactory correlation of the kinetic results.

Others (H. C. Brown, J. D. Brady, M. Grayson, and W. H. Bonner, J. Am. Chem. Soc. 1897 (1957) )» on the other hand, report that in the hydrolysis of alkyphenyldi- methylcarbinyl chlorides, C-C hyperconjugation is 80$ as effective as is C-H hyperconjugation. The arguments were based on the kinetic free energies of this alkylphenyl- dlmethylcarbinyl chloride system.

For the purposes of this discussion it will be as sumed (following Taft) that C-C hyperconjugation is much less effective than is C-H hyperconjugation. rate somewhat. The four methyl groups also introduce con-

siderable strain due to repulsions of eclipsed methoxyl, ft methyl groups and hydrogens on the ring. To what extent

To prepare 2,2,4,4-tetramethylcyclobutanone dimethyl ketal, the mixture of 2,2,4,4-tetramethylcyclobutanone, trimethyl orthoformate, methanol and catalyst had to be refluxed for 24 hours to force the reaction to completion. Normally, mere standing at room temperature or even at 0° for 2-24 hour is sufficient to produce a high yield of ketal. Whatever factors operate to slow down the ketal-forming reaction may well accelerate the reverse, hydrolysis, reaction.

the Inductive effects of the methyl groups come into play is not clear, but an alpha methyl group generally increases the reaction rate slightly (Table 20). Crowding at the re action site should sterically inhibit solvation (46), which in turn should slow the hydrolysis. In addition, strain in

(46) E. L. Eliel, "Substitution at Saturated Carbon Atoms," Chapter 2, p. 70; of M. S. Newman, "Steric Effects in Organic Chemistry,11 John Wiley and Sons, Inc., New York, N . Y., 1956.

the trigonal transition state, possibly due to increased methyl-hydrogen repulsions (see discussion of rates of five- membered ring ketals) should tend to slow down the hydroly sis. The net experimental result is a decrease in the rate of hydrolysis of 2,2,4,4-tetramethylcyclobutanone dimethyl 57 ketal by more than one-half when compared to that of cyclo-

butanone dimethyl ketal. Which of the factors listed will

be the most Important Is not known. It is clearly not the

repulsive strain of the methoxy1-methyl group-hydrogen

Interactions in the ketal, since this would be expected to

accelerate the reaction relative to the cyclobutanone dimethyl

ketal.

Tables 13 and 14 indicate that a moderate increase in the reaction rate was obtained in the hydrolysis of cyclo hexanone dimethyl ketals containing methyl substituents

(cyclohexanone dimethyl ketal 1.00; 3 ,3-dimethylcyclohexanone dimethyl ketal 1.8; 3,3,5,5-tetramethylcyclohexanone dimethyl ketal 3*3, Table 14). On the other hand the cyanohydrin (Table 18) and the hemiketal (Table 19) equilibria

show a promounced decrease in the stabilities of the addi tion compounds. The equilibria were pushed far over to the ketone plus alcohol side when methyl groups were present

In the three and five positions of cyclohexanone. The pres ent (Table 14) kinetic results can be explained in terms of

"axial crowding" (41,45). Models of the two ketals show that in the 3,3-dlmethyl derivative there is some 1,3 interac tion across the ring, between the axial methyl group and the axial alkoxy oxygen. This interaction increases even more in the 3,3,5,5-tetramethylcyclohexanone dimethyl ketal,

In which there is 1,3 and 1,5 interaction, axial methyl groups with the axial methoxyl. 58 The interactions described should be somewhat relieved when methyl alcohol leaves in the rate-determining step; the interactions between the alkoxide group and the methyl groups are removed. This interaction seems to be accumulative, the rate of the 3 »3-&imethyl ketal is 1.8 (relative to the unsub stituted ketal) and the 3 »3>5»5-tetramethy1 ketal reacts almost twice as fast (3*3)*

The kinetic enthalpies (Table 13) for hydrolysis of the cyclohexanone, 3 »3*-&imethylcyclohexanone, and the 3»3»5»5- tetramethylcyclohexanone dimethyl ketals Increase slightly in this order; the kinetic entropy terms show fair Increases in the same direction.

FBEE ENERGY RELATIONSHIPS OF REACTIONS OF CYCLIC MOLECULES

Useful correlations between the rates of reactions of various molecules have long been sought by physical organic chemists. The Hammett relationship has had considerable suc cess in correlating the rates of reactions of aromatic com pounds (^7)* Recently Taft-type free energy relationships

(21) have become of use in correlating the rates and

(4?) H. H. Jaffe, Chem. Rev., 32, 191 (1953).

equilibria of reactions of aliphatic molecules. It is of interest to discover whether such relationships exist 59 between the rates and equilibria of various reactions of cyclic molecules.

A satisfactory correlation has been found (^8) upon

(ij-8) H. C. Brown and K. Ichikawa, Tetrahedron, 1, 222 (1957). plotting the rates of reduction of cyclanones by sodium borohydride against the corresponding cyclanone-cyanohydrln equilibria. Only a limited relationship was obtained be tween the logarithms of the reduction rates of cyclanones by sodium borohydride and the acetolysis of corresponding cyclanol tosylates, and none at all for the hydrolysis of cycloalkylmethylchlorides and the reductions by sodium boro hydride. Figure 3 shows that the data of the present investi gation yields a general linear relationship when the log arithms of the rate constants of hydrolysis of 1-chloro-l- methylcycloalkanes and hydrolysis of cyclanone ketals are plotted.* The fit is not totally quantitative but certainly indicates a general correlation. The correlations are much less satisfactory when the logarithms of the rates of hy drolysis of ketals are plotted against: the logarithms

In Figures 3 ^ some values had to be estima ted (rates of ketal hydrolysis for and cyclanone dimethyl ketals; rates of chloride hydrolysis for 0^2 821(1 c oaih o I-Mty -hoo yln Hydrolysis. Cyclone I 1-Chloro -Methyl - of Logarithm ( I - Methyl — |- chloro cyclone hydrolysis, 25°) iue * oaih o Ccaoe ea Hdoyi vs. Hydrolysis Ketal Cyclanone of Logarithm 3* Figure 4 - n k In □ □ 2 ktl yrlss 0°) hydrolysis, (ketal +2 O -12 -14 0-6 -siae te n k In the -Estimated □ O-iO mty clrds |, CM) C|2, chlorides (methyl 0-9 0-5 + 4 0-8 0-7 + 6

0 6 61 1-chloro-l-methylcycloalkanes). This was carried out by linearly Interpolating between the next higher and the next lower cyclanone or 1-chloro-l-methylcycloalkane.

of acetolysls of cyclanol tosylates (Figure 4); logarithms

of the cyc}.anone-cyanohydrin equilibrium constants (Figure

5); or the rates of reduction of cyclanones by sodium borohydride.

It has been suggested (48) that a deviation from

linearity of a free energy plot parallels the difference

in steric bulk at the reaction site. Thus the sberic re

quirement of each component of the cyanohydrin (equilibrium)

and ketone (reduction) reactions as well as that for the

ketal (hydrolysis) and 1-chloro-l-methylcycloalkanes (hydroly

sis) reactions should be approximately equal and yield linear

relationships. The other pairs have steric effects which are not comparable and do not yield linear relation

ships.

The steric requirements of a substituent on a cyclic molecule should affect the conformation of the ring, par

ticularly that of the larger, more flexible rings. The

smaller and more rigid a cyclic molecule is the less it

should suffer distortion upon introduction of substituents.

If two different substituents are of approximately the same

size then they should affect the conformation of a cyclic eas s Logarithm o Aeoyi o Ccao Tosylates. Cyclanol of Acetolysis of m h t i r a g o L vs. Ketals In k| (acetolysis of cyclanol tosylates, 70°) o Figure L o g a r i t h m of Hydrolysis of C y c l a n o n e Dimethyl Dimethyl e n o n a l c y C of Hydrolysis of m h t i r a g o L Figure -2 ! 3-0 4 1 - 0 n (ea hdoyi, 0°) hydrolysis, (ketal 2 k In

+ M +6 M +2 O 0-12 0-6 -The I k2 f h ketal the of 2 k In e h T □ - 9 - 0 5 - 0 yrlss ee estimated were hydrolysis o-e 7 - 0 62 a* 3 a> (cycmohydrin, 2 5°) s Lgrtm f ylnn Dmty Ktl yrlss Rate. Hydrolysis Ketal Dimethyl Cyclanone of Logarithm vs. + I -3 -7 -4 -6 O Figure Figure -4 5 Lgrtm f ynhdi - eoe Equilibrium Ketone - Cyanohydrin of Logarithm * 2 + +4 +2 O -2 _J n k In ______2 ea hdoyi, 0°) hydrolysis, ketal ( 0-12 14 -1 0 I ______0-6 I ______o-io 9 - 0 5 - 0 L_ 0-8 0-7 + 63 6

6k ■» molecule In approximately the same manner. Hence, when

*• Steric requirement Is clearly not the only factor to Influence the rates of these reactions. Solvation, van der Waal's repulsions, etc. will also be very important.

reactions are carried out on two series of cyclic molecules

which have different substituents but of equal steric re

quirement, the molecules of this pair of series would be

expected to have very similar conformations in both ground and transition states and may therefore, yield a linear plot of the logarithms of the rate constants.

The results of Brown and Ichikawa (4-8) as well as those of this Investigation support this reasoning. The

steric requirements in the ground and transition states of the 1-chloro-l-methylcycloalkane and the ketal should be approximately equal as may be the steric requirement of the ketone-cyanohydrin pair. The limited relationship between the acetolysis of tosylates and the reduction of cyclanones by borohydride can be attributed to the differences In the sberic requirements of the substituents in the ground and transition states. It has been shown (21) that a reaction rate, in non- cyclic systems, is a linear function of substituent con stants a**. These substituent constants are characteristic 65 of the polarity of the groups attached to the reaction site,

they are additive, and they do not depend upon the type of reaction which the molecule is undergoing.

According to Taft's (21) arguments the rates of reaction of cyclic molecules should be correlated by such a function. If this were so, then Figures 4 and 5 and the other non-linear plots should not show this wide divergence from linearity. The divergence shows that additional fac tors such as the solvation, and particularly the steric requirements of the molecule must be considered. The linear plot of Figure 3 (hydrolysis of ketals vs. hydrolysis of 1-chloro-l-methylcycloalkanes and the other linear plot

(reduction of cyclanones by borohydride vs. cyanohydrin equilibrium) illustrate that when the steric requirements of reactions of corresponding molecules are similar, and other factors are either negligible or similar, a free energy relationship may be established.

In summation the following can be said:

1) In reactions of these cyclic molecules only those pairs will yield Hammett-type free energy relation ships in which the conformation of the molecule used for the kinetic experiments is approximately the same as that of the molecule used for the thermodynamic experiments. 2) In order for a linear relationship to exist 66

between the rates of different reactions the steric re

quirements of corresponding molecules must be similar.

3) The cr "constants" in the Taft-type free energy

relationships are constants only when the steric require ments of the various reacting molecules are comparable

(providing other factors such as entropy, van der Waal's repulsions, and solvation are also comparable or unimpor tant ). EXPERIMENTAL

The carbon-hydrogen analyses were carried out by

the Galbraith Laboratories, Knoxville, Tennessee.

Equipment

Constant temperature bath. The constant temperature

bath was an eleven liter wlde-mouth Dewar vessel enclosed

by a wooden frame. Clamps, suitably attached to vertical

steel rods, were used to hold the reaction tubes, heater,

etc. in place in the bath.

For the experiments at 0°, crushed ice and distilled water were used. The mixture was stirred vigorously through out the kinetic experiment. The temperature was controlled to io.01°, but some changes in the temperature were noted when different batches of ice were used.

In order to maintain temperatures above 0°, the bath was cooled by tap or ice water circulating through a copper coll immersed in the bath and by simultaneous heating with a controlled 250-watt heating element. This heating element was operated by the thyratron circuit, modified by separating the heater and plate and inserting an &utotransformer into the a-c line to the plate circuit.

The bath and temperature regulating equipment was virtually the same as that described by: P. W. K; Flanagan, Ph.D. dissertation, The Ohio State University, 1957» P- 88, Figure 2. 67 68 The voltage to the plate circuit could be varied between

k-S and 130 volts, with a consequent variation of the

heating element voltage. The bath was stirred by a Cenco

cone-driven stirrer. The thermoregulator was of the stand ard mercury-toluene type. Correct setting of the trans former voltage and proper immersion of the cooling coil allowed the temperature to be controlled to less than ^0 .01°.

For the two temperatures below 0° the potassium chloride-water (sat’d. KCl)-lce and sodium chlorlde-water

(sat'd. NaCl)-ice eutectics were employed. Here, finely crushed ice was added to the salt-water slurry; the mixture was stirred constantly and vigorously. The temperature control was again excellent, ±0.01° or better.

Temperature measurements. A -30° to +25° mercury thermometer was employed between -21° and +16°. This thermometer was calibrated point-by-point against a plat inum resistance thermometer. The platinum thermometer had been checked at the ice point and the transition point of sodium sulfate decahydrate (3 2 .3 8 3°)• The temperature at

28° was measured by a Beckman thermometer which had been calibrated at the transition point of sodium sulfate deca hydrate. 69 Reaction tubes. These were the same as described

by Matuszak (49). A reaction tube is diagrammed in Figure 6.

(49) C. A. Matuszak, Ph.D. dissertation, The Ohio State University, 1957 > P* 103» Diagram II.

It was necessary to pretreat these tubes in order that reproducible rates could be obtained. This pretreat ment was conducted as follows. After a thorough cleaning with soap and hot water the tubes were allowed to stand in hot (5 0°) cleaning solution (5 0) over night, then thoroughly

(5 0) N. A. Long, "Handbook of Chemistry," 8th Edi tion, Handbook Publishers, Inc., Sandusky, Ohio, 1952, p. 1816.

rinsed with distilled water and steamed. To carry this out the reaction tube and head were mounted in an inverted posi tion. Steam, generated from distilled water, was blown into the tube through its liquid outlet. The steam condensed on the tube sides and the condensate was discharged through the head outlet. After steam, generated from about ?00 mis. of water, had been forced through, the tube was dried by blowing in filtered air. After each kinetic run the tubes were washed thor oughly with distilled water followed by grain alcohol (95% aqueous ethyl alcohol, not denatured). They were then 70

3-4 cm Stopcock

7 cm.'

34 45 > - Spring fastener

Capillary tubing

2 3 -33cm.

Reaction solution

REACTION VESSEL (Figure 6) steamed out and dried as described previously.

This steaming procedure proved to be Important in maximizing the reproducibility of the kinetic runs, particu larly those carried out at low acid concentrations (less than 2 x 1 0 moles/liter).

Ultraviolet spectrophotometer. This was a Beckman

D. U. model. The cells employed were of quartz. Care was taken to keep these cells clean.

Sample bottles. These were 25 ml., wide-mouth, glass bottles capped with a polyethylene stopper. The bottles were carefully washed with soap and hot water after each run and rinsed thoroughly with distilled water prior to drying. The caps were rinsed with distilled water repeat edly and air-dried.

Volumetric equipment. All volumetric equipment used was calibrated with distilled water at 20°. The 5 j 10, 25» and 100 ml. pipettes and the 10 and 20 ml. hypodermic syringes (Becton-Dickenson Co., Yale-Luer-Lok type) were calibrated from the weight of 20°, distilled water which they discharged.

Kinetic procedure

A typical experiment was conducted as follows.

Solvent (usually 100 ml.) and diluted acid catalyst (5*00 72 or more ml.) were both measured into the reaction vessel

with calibrated pipettes at 20°. The reactor tube was then

immersed in the constant temperature bath for at least one

hour, usually over-night. A clean glass rod, which had

been flattened out on one end to form a plunger, was used

as a mixing device. Simultaneously the top of the reaction

vessel was placed into an empty reactor tube which had also

been immersed in the bath. The long sample tube was there

by brought to the same temperature as the catalyst-solvent solution.

The pure ketal, which had been stored in a glass-

stoppered, polyethylene film-sealed bottle at -20°, was

weighed in a 5-ml. syringe. This was carried out by weigh

ing the entire syringe, containing 0.3 to 0.8 ml. of ketal

plus a small cork stopper on the needle end, on an analyti

cal balance. The ketal was then quickly injected into the

solution of ca,talyst and solvent, the stopwatch started,

and the solution vigorously agitated with the glass plunger- mixer for JO seconds. The reactor head was put in place and secured with a wire spring. The syringe plus cork

stopper was then weighed. The difference in weights represents the amount of ketal added.

■* The rate constant of this first order or pseudo first order reaction is Independent of the amount of react ing ketal. The weight of the ketal added was noted as a 73 matter of record and also to check on the self-consistency of the optical densities at "time infinity."

Samples were withdrawn by quickly applying nitrogen pressure through the gas inlet of the reactor head and thereby forcing the liquid up the sample tube. The first

1-3 ml. of solution were discarded; the following 7-10 ml. were caught In a 25 ml. sample bottle. This bottle con tained one or two drops of aqueous potassium carbonate*

(10^> by weight). The sample bottle was quickly stoppered

The potassium carbonate was used to quench the reaction. Two drops of the potassium carbonate solution were used when the acid condentration of the solvent was greater than 5 x 10”3|J. One drop of the carbonate solu tion contains 1 x 10” moles of base (18 drops/ml. solution). If the solvent is 10-2n in acid (the highest catalyst con centration employed), then two drops of carbonate solution is equal to 200^ of the base required to neutralize the acid catalyst of a 10 ml. sample. The use of one or two drops of the carbonate solu tion does not affect the optical densities of the solution appreciably. Seven to ten ml. of solution represent 130- 180 drops of liquid. Since the same amount of carbonate is added to each bottle, the only real error introduced is due to the difference in the volumes of reacting solution transferred Into the bottle. This error must be much less than one per cent. Errors introduced by this technique are well within the range of random errors i3-^%) usually asso ciated with kinetic procedures of the present type.

and shaken vigorously for approximately 15 seconds. Nine samples were taken during each run, usually at constant 7^

time Intervals. The last (tenth) sample was obtained after

at least ten half-lives had passed since the start of the

reaction.

The samples were analyzed with a Beckman D. U. spec

trophotometer at a wavelength corresponding to the maximum

absorption of the ketone. When 0.3 to 0.8 gm. of ketal was

used for each 100 ml. of solution, no further dilution of

the solution was necessary since the ma.ximum optical densi

ties were between 0.5 and 1.0.*

A plot of the optical density (at too ) of each run was made against the ketal concentration (gm/100 ml.) for all runs of each ketal and from these data the s at A. max. calculated. For the cyclohexanone dialkyl ketals the re sults were as follows; at 280.5 m/i. ; dimethyl 16.6, diethyl 16.5» dilsopropyl 1?.0. The cyolobutanone and cyclopentanone dialkyl ketals yielded similar results. These results indicate that there is no appreciable hemiketal formation of the ketones and the alcohol produced in the reaction.

This procedure was modified somewhat for the hydroly

sis of cyclotetradecanone dimethyl ketal. This ketal is a

solid and does not dissolve rapidly in the acid-solvent mixture. Therefore, the ketal was first dissolved in the neutral solvent and at time zero thermally-equilibrated catalyst solution was added vis, a calibrated syringe. All other manipulations were the same as in the standard pro cedure. Cyclotetradecanone dimethyl ketal is stable to hydrolysis in a neutral solution. 75 Calculations

The integrated first-order rate law equation in

terms of optical densities is (5 1)

O.D.qo — 0 .D. Q ^ = ln O.D.qo - °*D -t

(51) A. A. Prost and R. G. Pearson, "Kinetics and Mechanism," John Wiley and Sons, Inc., New York, N. Y . , 1953, P. 37.

where:

is the first-order rate constant in units of tlme“l. t is the time. O.D.qq is the optical density of the solution after ten or more half-lives. 0.D.o is the optical density at time zero. O.D.£ is the optical density at time t

The 0.D.o is determined as follows. A known weight of pure ketal was placed into a 25 ml. volumetric flask and diluted to volume with solvent. Seven to ten ml. of this solution were mixed with one or two drops of 10$ potassium carbonate solution (the amount of carbonate solution used depended upon the acid concentrations which were to be employed in the hydrolysis reaction, see above).

The optical density of this ketal solution, compared to pure neutral solvent, was then determined. To calculate the O.D.q of a particular hydrolysis reaction the following equation (Equation 17) was used. /volume of \ /Weight of ketal\ standard ketalj [ in hydrolysis J O.D. of stand V solution______/ I reaction______' (1?) (ard ketal '’Weight of ketal\/Volume of \ solution in standard Jlhydrolysls 1 l solution /(reaction /

For example, 0.1321 gm. of ketal was weighed into a

25 ml. volumetric flask and diluted to volume with neutral

solvent. This gave a solution with an O.D. of 0.013 at

the X max. of the corresponding ketone. A hydrolysis reac

tion was then conducted in which 0.5382 gm. of ketal was hydrolyzed in 104.92 ml. of solvent-catalyst. The 0.D.o

is calculated as (Equation 18)

° - D - ■ ( 0 •0 X 8 J ( o o f t l ' x" l O ^ f l ) = ° - 01 7 <18)

O.D. - O.D. In ---■ °P — is then calculated for each u,u*oo “ u,u*t sample at time t. These values are plotted against t. The points should form a straight line which goes through the origin. The slope of this line is the first-order rate constant k^ in units of time-1.

To calculate the second-order rate constant the first-order constant is divided by the catalyst concen tration of the hydrolysis soliition.

The catalyst concentration is determined as follows

(Equation 19). 77 Volume of 0.IN Catalyst concentration (moles/1.) 0.1019 stock acid , 1000 j solution j

1 olume of neutral + Volume of diluted solvent catalyst solution

x Density of solvent at reaction temperature Density of solvent at 20° (19)

The ratio of the solvent densities corrects for the change

in volume with temperature and therefore the change in

catalyst concentration with temperature. The reference is

always 20°, the temperature at which the solutions were made up and measured.

Special calculations for the hydrolysis of the ten-membered ketal

The cyclodecanone dimethyl ketal could not be

obtained in pure form (vide infra) and it was known to

contain of the corresponding methyl enol ether.

Since the cyclodecanone methyl enol ether could be obtained in pure form (vide infra), in a separate preparation, a competitive experiment was carried out to determine the rate constant of the pure cyclodecanone dimethyl ketal. The cyclodecanone methyl enol ether was hydrolyzed in the same manner as the ketals. The calculations yielded good first order plots. The first and second order rate constants were calculated from these data.

Then the impure cyclodecanone dimethyl ketal was hydrolyzed as described above. Prom the O.D.qq obtained here, a value corresponding to lk.h% cyclodecanone methyl enol ether (as the ketone now) was subtracted. No correc- tion was applied to the measured O.D.j.. With this cor rected O.D.oo, the experimental 0.D.o , and O.D.^'s, the

The O.D.^'s measured are the sum of the O.D.-fc due to the enol ether and ketone hydrolyses. Under the condi tions of the reaction, the contribution to the measured O.D.t of the ketone from the enol ether hydrolysis would be at most 1/100 of the corresponding contribution of the ketone from the hydrolysis of the ketal. Hence, no cor rections were applied to the O.D.t* The plots gave good straight lines, indicating that first order kinetics were being followed.

first and second order rate constants for the pure ketal could be calculated in the usual manner.

This procedure probably lowers the accuracy of the rate constant of the ten-membered ketal somewhat, yet this seemed to be the only practical way of solving the problem.

Activation energy and entropy calculations

By plotting In k2/T against 1/T, a straight line is rp. tf: obtained, the slope of which is AH /R. From the slope AH 79 Is calculated* In order to find AS , AH y sind the appro

priate pair of k2 and T are substituted Into the following

equation (Equation 20) (52).

(52) A. A. Frost and E. G. Pearson, "Kinetics and Mechanism," John Wiley and Sons, Inc., Mew York, N. Y . , 1953, P. 98.

k2 - IT eAS*/H • e-AH^ T (20)

On substitution of the natural constants and rearrangement,

Equation 21 is obtained.

AS1" = R In k2 + E In k2/T + AH*/T - 55-36 (21) where

R = 1.987 cal./deg.-mole T = temperature (°K) k - Bolzmann's constant (erg/deg.) h = Plank's constant (erg-min.) k2 = second order rate constant (l./moles- min.)

The AS was obtained for each temperature at which the

compound in question had been hydrolyzed. The average of these AS 1s is reported. 80 Preparation and Purification of Chemicals

The b.p. and m.p, temperatures are not corrected.

Solvent preparation

The dimethyl ether of ethylene glycol (53) was washed with concentrated hydrochloric acid, which had been

(53) Ansul Ether 121, Ansul Chemical Company, Marinette, Wisconsin.

saturated with sodium chloride or calcium chloride, in

order to remove an odoriferous impurity (probably an amine).

One washing and subsequent drying over calcium chloride, potassium hydroxide, and then refluxing over calcium hydride and sodium followed by distillation gave a solvent of good

quality, free of foreign odor.. n^° 1.3796 lo.oooo, b.p. 84-86°; lit. (54) n^° 1 .3792, b.p. 85.2°.

(54) Chemical Product Bulletin, Ansul Chemical Company, Marinette, Wisconsin.

A 50:50 mixture by volume of this ether and water did not result in a solvent which could dissolve the 81 cyclotetradecanone dimethyl ketal in appreciable concentra tion. Therefore, a solvent mixture was prepared by adding to three volumes of water enough freshly distilled ether to make a total volume of ten parts at 20°. The addition of this ether to the water results in heat evolution and vol ume contraction.

This solvent (n^° 1.3792) was made up in one-liter, volumetric flasks and stored in a stoppered, clean, one- gallon bottle. Tests for peroxides, using acidified potas sium iodide - starch paper, showed little, if any, oxidis ing agents to be present. Usually the solvent was used within one week after its preparation.

Catalyst solutions

Hydrochloric acid was employed as the “catalyst.1'

At the beginning (12/2/57) and near the end (6/18/58) of the present experimental studies the one-gallon stock

(water) solution was found (55) to be 0.1019 normal in

(55) H. H. Willard and N. H. Furman, "Elementary Quantitative Analysis," 3rd Edition, D. van Nostrand Co., New York, N. Y . , 1940, pp. 139-140, 150-154.

acid. No change in acid concentration was detected over this period of time. 82

The diluted catalyst solutions were prepared by

adding a known volume of the acid to a one-liter volumet

ric flask, next adding sufficient triple-distilled water

to make a total volume of 3QQ ll ml. and "making the solu

tion up to the mark" with purified dimethyl ether of

ethylene glycol. This mixture was stored in the same con

tainer in a 20° constant temperature room until used.

It is noted that the diluted catalyst solutions have the same water-to-ether ratio as the solvent proper, namely three volumes of water made up to ten volumes of

solvent. Therefore, mixing of the diluted catalyst solu

tion and the neutral solvent does not result in a change in volume.

Densities of the solvent

The densities of the solvent were determined in a

25-ml. pycnometer at the temperatures of the kinetic runs.

Thus, a clean, dry, weighed pycnometer was filled with dis tilled water and allowed to equilibrate thermally for at least one hour at the desired temperature. The vessel was quickly removed from the bath, dried, and then weighed. The difference in weights multiplied by the known volume of water, at the particular temperature (56) yielded the

(56) N. A. Long, "Handbook of Chemistry," 8th Edi tion, Handbook Publishers, Inc., Sandusky, Ohio, 1952, pp. 1219-1221. ©3 pycnometer volume. This procedure was repeated with the pure, neutral solvent. The weight of the solvent divided by the volume of the pycnometer resulted in the solution density at the temperature in question. The following data were obtained.

Temperature (°)# Solvent density (g./ml.)

28.16 0.933 20.0 0.944 15.86 0.9**5 15*32 0.945 7.83 0.953 -0.04 0.960 -IO.69* 0.972 -21.13 0.980

* The pycnometer volume below 0° was measured by using distilled mercury as the fluid.

Preparation and Purification of the Ketones

(The physical properties of the purified ketones and the corresponding literature values are listed in Table 21.)

Cyclopentanone was purchased from the Matheson Com pany, Norwood, Ohio. Cyclohexanone was received as a gift from the E. I. duPont de Nemours and Company, Wilmington,

Delaware. Cycloheptanone and cyclofictanone were bought from the Columbia Chemicals Company, Columbia, South Caro lina. The cyclononanone and some cyclodecanone were TABLE 21

b .p . ( ° /m * ) m.n.l I /',n a x , ♦ Ketone found lit, (a'ef.) found lit. (flef.J found lit. (Kef,) Senicarbarn n,o,(°) 6 max, U > ) found l i t , m Cyclobutanone 97,5-98,2 9S.2/743i48) .. 1,4207 1 .4 20 9(48) 277 18,4 £ ,2 ,4 ,4-Tet ramethy1 eye1obutanone 128,5 128,0-128,5/745' ' ■ ■ 1,4144 215-216 201-22l ! 87) Ketone purified via distillation. 507,5 18,0 2-fethylcyclopentanone 138-140 135-1361 J -• 1,4350 193,5-195,5 192*194!??) U385iL 290 14,5 177-178.5 170 -1 71 1 Cyclopentanone 128,5-129,5 1 3 0 ,5 ^ ) *• 1,4371 1 .4 3 6 3 '48) 1 8 8 ' tic nrenaration 287 18,3 212-214(deo.) 206l8) . ■ 3,3-Bimethylcyclopertanone 59,0-59,2/27 152-153/748W1 1,4344 l,4550(d)(ffl 287,5 19,9 180.5 Cyclohexanone 162,5-153,0 153,8/744l4®) - ■ 1.4456 1,4502(48) 178 W 232,5 15,7 - m 2-Methylcyoloheianone 151-162 165-166(8) ■ ■ 1,4482 l,4 49 2< e ) Eetone p u r if ie d v ia b i s u l f i t e a d d itio n compound 286 13,5 157,5-183,5 19l}e j Eetoile ramfifiS in. 3,3-IMhylcyclohexanone 177-180 63-66/l4lf) ■ - - . 282,5 17,4 194-196 155-195^) 3,3,5,5,-Tetramethylcyclohexanoiie 81-83/11 59-6l/5,5^^| . m 1,4521 1,452 o( 5S) 288 15,5 217-219 2 1 7 -2 is!® ) Cyclo|eptanone 66,8-67,3/15 66,5-e6,0/l5ly ■ I' 1 1,4617 l ,4 6 1 l( s ) 284 19,3 162-165 162-163lo) Cyclooctanone 39-41 •. 85.5-87,5/13 90/12 7 , 4 0 - d ll1 ' 284 16,4 170-172 170-17 n o ; Cyclononanone 86,5-88.0/9,5 97.5/15™ 25,6 • 1.4781 1 .4 74 5(43) 235 15.4 182-193 181.5-18£(66) Cyclodecanone 101.0/1 0 % -m /^ 24,5 24.5-25,oj48! 1,4809 1 ,4 8 0 9 (85) 234 Cyclododecanone • ■ 6 0,5-61,0 6 1 -6 ?(48) .. 14,2 198-200 203-205(S8) Cyclotetradecanone ■ 50,5-52 ,5 52, O W . m 281 21.4 214,5-215,5 218-219(86) 281 22.6 Di-n-propyl ketone 141,2-143,0 145/767' , » •1. 3 1,4071 1 ,4 0 6 9 (1) 195,5-197,5 1981s6 ) 1.3i(k:) Di-n-hexyl ketone 130,3-130,7/11,5 137.6/12' J 31-32 3 2 , 5 ^ 280.5 16,5 133-134 251 2 0 ,8 .. letone purified via distillation

Measured in the kinetic sohent.

a) A I. Vogel, J. Chen. Soc., N. Basarov, Invest. Akad, M S.S.H., Otdel. fin, M , 838 (1853); c.A, 48, 1082-3 (1955), S. Bracing and J. A. Hartman, J. Am. Chen. Soc,, 75, 938 (1953), ~ dj I Benshall, J. Soc. Chen. Ind., 62, 127 "" B, Carlin and H. P. Landerl, jTlm . Chen, Soc,, 75, 3989 (1963), B i'hi, o, Jeger, and L. Euzieka, Helv. Chin, Acta, 31, 241 (1948), Vogel, J, Chen. Soc., 2032 (1928), Tohoubar, Conpt, rend,, 215, 224 (1942), i ) L M c k a , 11, S to ll , H. I . f y s e r , and 1 , 1 , Boeketioogen, H elv, C hin, A cta, 13, 1152 (]9 3 0 l, j ) A. 1, Bloonouist and L, 3, Lui, J. An, Chen, Soc,, 75, 2153 (1953), ~ k j D. I Cowan, G, 3 . Jeffsry , and A, I . V ogel, J , CheaT Soc,, 171 ( 1949 ), 1) E. E, Dreger, 0 ,1. Keim, G. D. lie s , L, Shsdlmky, and j, EosSj\nd] Eng, Chen,, 35,510 (1944), purchased from L. Light and Company, Bucks, England. The

di-n-hexyl ketone was purchased from the Sapon Laborator

ies, Valley Stream, New York.

The following ketones were received as gifts from

Dr. K. Greenlee of The Ohio State University Research

Foundation; American Petroleum Institute Project 45:

3,3-dimethylcyclopentanone» 3»3“dime'thylcyclohexanone, 2-methylcyclopentanone, and di-n-propyl ketone.

Cyclobutanone was prepared (57) by rearranging penta-

(57) J* Roberts and C. W. Sauer, J. Am. Chem. Soc ZI. 3925 (1949). erythritol tetrabromide (58) with zinc dust to methylene- cyclobutane and subsequent oxidation of this olefin to the

(58) H. B. Schurink, Organic Syntheses, Col. Vol. II 2nd Edition, John Wiley and Sons, Inc., New York, N. Y., 1943» p. 476. It is best to change this procedure somewhat. The reaction was carried out in a flask fitted with a heavy duty stirrer (teflon blade). The maximum temperature was kept at 165-175°. During the heating above 135° a consider able amount of white phosphorous deposits on the reactbr*. walls. These deposits are best destroyed by burning in air in a well ventilated hood. The water-washed crystals of tetrabromide also contain white phosphorous. This material can be removed by drying the solids on a hot steam plate (glass dish) in the open air for several hours with frequent mixing. The crude, dry tetrabromide is best purified by ex traction with boiling carboem'tetrachloride, filtration, and 86 crystallization from this solvent. Two such recrystal- lications yield a white, odorless product.

The best yield obtained was 65%> based on the alcohol (the reference claims 78-82^). The phosphorous tribromide used (Eastman Kodak, white label and also Dow Chemical Company, technical grade) was not redistilled before use.

ketone in 18^ yield. n^0 1.4207, b.p. 97.5 - 98.2°, semicarbazone b.p. 215-216° dec.; lit. (57) 1.4209, b.p. 98-100°, semicarbazone m.p. 201 to 221° (wide range of values given).

The 3,3,5,5-tetramethylcyclohexanone was prepared by the cuprous chloride catalyzed 1,4-addition of methyl magnesium iodide to isophorone (59)» 3%% yield; b.p. 81- 83°/ll mm.; n^° 1.4521, semicarbazone m.p. 217-219° dec.;

(59) M. S. Kharasch and P. 0. Tawney, J. Am. Chem. Soc., 62, 2308 (1941).

lit. (59) 1.4520, b.p. 59-6l°/5.5 nim., semicarbazone m.p. 217-218° dec. The ketone was purified through its semicarbazone. The 2-methylcyclohexanone was prepared from 2-methyl- cyclohexanol by dlchromate oxidation following the general procedure of Vogel (60). The ketone was purified by

(60) A. I. Vogel, "Practical Organic Chemistry," 3rd Edition, Longmans, Green and Company, New York, N. Y. 1956, p. 337. fractionation through a 12-inch helix-packed column, reflux

ratio about 10:1. n^° 1.4492, b.p. 161.0 - 161.7°, semi

carbazone m.p. 187.5 - 188.5°; lit. (60) n^° 1.4475, b.p.

165°, semicarbazone (61) m.p. 185-7°.

(61) J. H. Boyer and F. C. Canter, J. Am. Chem. Soc., 22* 1280 (1955).

In order to prepare the 2,2,4,4-tetramethylcyclobutanone (6 2), isobutyry][chloride was reacted, in benzene

(62) H. L. Herzog and E. R. Buchman, J. Org. Chem., 16, 99 (1951). solution, with a 1.7 fold excess of triethylamine for 72 hours at 3Q~kQ° with frequent shaking. Filtration, wash ing of the solids, and evaporation of the solvent yielded dimethyl ketone dimer (2,2,4,4-tetramethylcyclobutane-

1,3-dlone) In 67% yield; crude m.p. 106-109°, lit. (62) m.p. 111.5-113.5°. The disemicarbazone was prepared (63) in 9^f° yield

(63) A. I. Vogel, "Practical Organic Chemistry," 3rd Edition, Longmans, Green and Company, New York, N. Y., 1956, p. 344. from the dione, m.p. 310° dec.; lit. (62) 297° dec. It 88

was found "best to carry out the reduction of the semicar

bazone to the monohydrazone as follows. Sodium (50 gm.,

2.17 moles) was dissolved in 500 ml. of ethylene glycol

in a large flask (3 1.). The solution was brought to 130°

and then the crude, dry semicarbazone (65 gm., 0.293 mole) was added. The temperature was raised slowly. Between

155-170° considerable gas evolved with much foaming (strong NH^ odor). Simultaneously a liquid, which distilled between

160 and 190°, was drawn off.*

* This appears to be the monohydrazone which, when left in the solution as the previous authors (62) suggest, will be reduced to the saturated hydrocarbon. This con densate has a very unpleasant odor. Prolonged breathing of it results in severe headaches.

The ethylene glycol mixture was refluxed, at about

205-208° for one hour (62.) and then cooled. One liter of water was added and the mixture steam-distilled until

500 ml. of condensate had been collected. The condensate did not contain much hydrazone.

This condensate was combined with the previously obtained distillate and 150 gm. of oxalic acid was a,dded.

Steam distillation and subsequent preparation of the semi carbazone gave 16 gm. of a white, crystalline solid; Jk.2% yield based on the dlsemicarbazone. The 2,2,i+,4-tetramethylcyclobutanone semicarbazone was recrystallized twice 89 from 95$ ethanol, and had a m.p. of 193.5-195.5°5 lit.

(62) 193-194°.

The ketone was regenerated from this semicarbazone with oxalic acid and fractionated through a 12-inch spinning band column, b.p. 128.5°; n^° 1.4144; lit. (62) b.p. 128-

128.5°/7^5 ram. The infrared spectrum (see Appendix) showed a strong carbonyl band at 5-51/*- with a. weak shoulder at

5. 45 j*~ • The latter seems to result from an impurity which could not be removed.

The cyclodecanone, cyclododecanone, and cyclotetra decanone were prepared by condensing the a,'W-dicarboxylic- acid dimethylesters in the presence of dispersed sodium in xylene to form the cyclic acyloins (64), and the reduction of these acyloins with zinc and concentrated hydrochloric

(64) N. L. Allinger, Organic Syntheses, Vol. 36, John Wiley and Sons, Inc., New York, N. Y., 1956, p. 79.

acid (65). The ketones were further purified by recrystal lization of their semicarbazones in alcohol, and regeneratiai

(65) A. C. Cope, J. W. Barthel, and R. D. Smith, Organic Syntheses, Vol. 36, John Wiley and Sons, Inc., New York, N. Y., 1956, p. 14. 90

by steam distillation with hydrochloric acid (6 N).

The cyclodecanone was fractionated through a helix-

packed, 12-inch column; b.p. 101°/10 mm., m.p. 24.5°,

1.4809, semicarbazone m.p. 198-200°; lit. (65) b.p.

99-101°/8 mm., m.p. (66) 24.7-25.0°, n20 (65) 1.4809,

semicarbazone mp. (66) 203-205°.

(66) V. Prelog, L. Frenkiel, M. Kobelt, and P. Barman, Helv. Chim. Acta, l?4l (1947).

The cyclododecsnone was chromatographed to remove

a yellow impurity. Fisher alumina (30 gm./gm. of ketone) was used with petroleum ether (b.r. 30-60°) as developer and a 90:10 mixture of petroleum ether-benzene as eluent..

The ketone was then vacuum sublimed, m.p. 60.5-61.0°, semi

carbazone m.p. 214.5-215.5°, lit (66) m.p. 60-61°, semi carbazone m.p. 218-219°. The cyclotetradecanone was vacuum sublimed and had the following physical properties: m.p. 50.5-52.5°, semi carbazone m.p. 198-199°; lit. (67) m.p. 52°, semicarbazone m.p. 198°.

(67) H. Hunsdieker, Ber., 2£> 1190 (1942).

The other ketones, except as listed below, were purified through their semicarbazones and subsequently 91 regenerated from an acid medium. Vogel's procedure (63)

for the preparation of the semicarbazones was found to be

excellent. The yields were usually between 80 and 95^.

It was found convenient to use a 10-20^ excess of semicar- bazlde hydrochloride and a 50% excess of sodium acetate.

The semicarbazones were recrystallized at least

once from boiling 95% ethanol. It was most convenient to regenerate the ketone from a concentrated, aqueous solution

of oxalic acid by steam distillation. Oxalic acid is suf

ficiently reactive to decompose a semicarbazone quantita

tively and yet not strong enough, as an acid, to cause

undesirable side reactions such as condensations, etc.

Cyclohexanone was purified (68) via its bisulfite

addition compound. The 2-methylcyclopentanone was purified

by double distillation through a 24-inch packed column.

(68) A. I. Vogel, "Practical Organic Chemistry," 3rd Edition, Longmans, Green and Company, New York, N. Y., 1956, p. 3^2.

Its Infrared spectrum (2-15/*- ) was identical in detail with

a synthetic preparation.

The triisopropyl orthoformate was prepared from

chloroform and sodium isopropoxide in isopropyl alcohol

(69). The yield of double distilled material was 7*7%',

(69) P . P . T. Sah and T . S . Ma, J . A m . Chem. Soc., 54, 2964 (1932). 92 b.p. 55.5-57.0°/10 mm., ng0 1 .3967; lit. (69) b.p. 166-

169o/760 mm., n^° 1.4000.

Preparation and Purification of Ketals

The physical properties and the elementary analysis

of the ketals are summarized in Table 22. All but three of these compounds are new.

A genere.1 procedure was adopted to prepare these ketals. The quantities involved may be scaled down consid erably (to 100 mg. ketone, etc.) in order to work out the exact conditions on small samples. The procedure found best is illustrated with the preparation of the dimethyl ketal of 2-methylcyclohexanone.

2-’Methylcyclohexanone (31*5 gm., 0.281 mole), trimethyl orthoformate (31*4 gm. 0.295 mole, 5% excess),

4f. The trimethyl orthoformate and the triethyl ortho formate were obtained from the Kay Pries Chemicals Company, 180 Madison Ave., New York, N. Y.

and absolute methanol (51.5 gm., reagent grade) were mixed in a stoppered 250 ml. flask. Five drops of a solution of hydrogen bromide (gas) in anhydrous methanol (about 1 N in hydrogen bromide) were added with mixing and the flask was left to stand at room temperature for six hours or longer. 93 TABLE 22

Physical Properties of Ketals

b.p. 20 % C* ~ %E* Compound (°/mm.) calc. found calc. found

Cyclobutanone dimethyl ketal 104.5 1.4118 62.04 62.19 10.41 10.48 Cyclobutanone diethyl ketal 131.5-132.5 1.4148 66.62 66.89 11.19 10.98 Cyclobutanone (''If'* diisopropyl ✓ \ ^ ^66.07^a' (-11.97',a' ketalW) 60.0-60.5/l3 (1.4091) ' 69.72 <66.15 11.70 L 12.12 2,2,4,4-Tetra- methyl cyclo butanone dimethyl ketal 61/18.5 1.4321 69.72 69.86 11.70 11.99 Cyclopentanone dimethyl ketal ^ 50.3/20^ 1.4264 64.58 64.35 10.48 10.82 Cyclopentanone diethyl ketal 52-53/n 1.4263 68.31 68.20 11.47 11.66 Cyclopentanone diisopropyl ketal 69.5-70.5/10 1.4330 70.92 70.70 11.90 11.77 2-Methylcyclopen tanone dimethyl ketal 64-65/31 1.4321 66.63 66.42 11.18 11.19 3,3-Dimethyl- cyclopentanone dimethyl ketal 53.5-54.0/13.5 1.4262 68.31 68.22 11.47 11.25 Cyclohexanone dimethyl ketal(°) 65.0-65. 5/16^ °^L. 4398 66.63 66.70 11.18 11.34 Cyclohexanone diethyl k e t a l W 69.0-69.5/11 1.4365 69.72 69.60 11.70 11.74 Cyclohexanone diisopropyl 86.0/10ketal 1.4433 71.95 71.74 12.08 12.26 2-Methylcyclo- hexanone dimethyl 74.0/18.5ketal 1.4469 68.31 68.52 11.47 11.67 3,3-Dimethyl- cyclohexanone dimethyl ketal 68.5-68.7/11 1.4429 69.72 69.99 11.70 11.74 3,3,5,5-Tetra- methylcyclohexanone dimethyl r 71*76 r 12.11 ketal 82.5/8.5 1.4500 71.95 1-71.93 12.08 12.28 94 T A B L E 22 (Continued)

* * ob/ P* 20 , %HS Compound ( /mm.) “D calc-. found calc. found

Cycloheptanone dimethyl ketal 77.0-79.0/l0 1.4513 68.31 68.34 11.47 11.29 Cyclooctanone dimethyl ketal 72.5-78.5/2-3.5 1.4604 69.72 69.92 11.70 11.88 Cyclononanone dimethyl ketal 69/1.5 1.4665 70.92 70.72 11.90 11.73 Cyclodecanone ( . r72.87( e) j-12.39^e) dimethyl ketal(®)97-98/2.5^e ' 1.4738^®^ 71.95 -jL 73.02 12.08 X-12.56 Cyclode canone '77.79 rll.78 methyl enol ether 64-65/2 1.4875 78.51 -jL77.84 11.98 \-11.73 Cyc1od ode canone dimethyl ketal 88-93/0.25 1.4761 73.63 73.76 12.36 12.52 Cyclot et rade canone dimethyl ketal (m.p.48.5-49.5) 74.94 75.02 12.58 12.45 Di-n-propyl ketone dimethyl ketal 51.0-51.5/8.5 1.4135 67.45 67.60 12 . 58 12.45 Di-n-hexyl ketone dimethyl ketal 141.0/l2 1.434-2 73.71 73.70 13.20 13.05

(a) Impure compound; probably 50% triisopropyl orthoformate- 50% ketal.

(b) J. Boeseken and F. Tellegen, Rec. trav. chim., 57, 133 (1938); b.p. 63-65°/20 mm.

(d) Reference (b), b.p. 78-85°/l8 mm.

(e) Contained 14*4% cyclodecanone methyl enol ether and a trace (<1%) of cyclodecanone.

* Analysis by Galbraith Laboratories, Knoxville, Tennessee. 95 At this point it was found best to check whether

all of the ketone had reacted. To do this about one ml. of

solution was withdrawn from the flask and added to 5-10 mg.

of solid potassium carbonate. The neutral liquid was care

fully placed on a rock-salt plate and the alcohol allowed to evaporate off. This also removes the methylformate which would interfere with the subsequent analysis for

unreacted carbonyl by infra-red (5-7-5.8/*-}. If the ketone had not reacted completely the solution was allowed to

stand somewhat longer, or more acid or orthoformate were added. Sometimes cautious warming helps.

When the reaction was complete, as judged by the

substantial absence of a carbonyl band on the Infra-red,

solid potassium carbonate (0.1 gm.) was added to neutral ize the catalyst. The liquid was rectified through a

12-inch packed column as follows:

Gut No. 20 Wt.(g m .) Yield {%) b.p. (°/mm.) D

1 62,5 to 64/760 _ 2 4.0 - pumped off 3 9.0 20.3 71-73.5/18 — 4 15.5 34.9 73.5-74.0/18.5 1.4469 5 10.0 22.5 74.0/18.5 1.4469 pot residue 3.0 — —— cold trap 6.0 - - —

The total yield of kinetic grade ketal (free of ketone and enol ether) was 57-4^. 96

The preparative yields of ketal may be improved significantly if small amounts of unreacted ketone and enol ether can be tolerated in the product. In these preparations only fractions containing no ketone or enol ether (as Judged by the absence of the infra-red absorp tions of the ketone and enol ether at 5.?yU- and 5.9-6.0^, respectively) were used.

It is of synthetic Interest in preparation of these ketals that there are always traces of the corresponding enol ethers formed {1-5%). Raising the reaction temperature Increases the yields of enol ether significantly,

* When the acidic solution is boiled then the enol ether formation Is quantitative. The length of boiling necessary varies somewhat; cyclodecanone dimethyl ketal eliminates alcohol at room temperature, while the cyclo hexanone dimethyl ketal had to be boiled for J-k hours to force about a complete enol ether formation.

It is best to allow the reaction to proceed at or below room temperature to avoid the formation of enol ether in appreciable quantities.

The cyclodecanone dimethyl ketal eliminates alcohol very readily. This ketal forms the enol ether even under basic or neutral conditions at elevated temperatures (^>50°). The ketal and its enol ether could not be separated by care ful rectification. A modified procedure for synthesis of cyclodecanone dimethyl ketal was used. 97 A mixture of cyclodecanone (17.0 gm., 0.110 mole),

trlmethyl orthoformate (40.0 gm., 0.3775 mole, 243^ excess), and anhydrous methanol (63.0 gm.) was chilled to 0°. The hydrogen bromide catalyst (0.5 ml.) was added, and the reaction was allowed to proceed over night at 0°. Solid potassium carbonate (1.0 gm.) was added and the solvent removed. About one-half of the remaining liquid was frac tionated through a 12-Inch column to remove unreacted cyclodecanone and trimethyl orthoformate. The pot residue was flash-distilled and the kinetic fraction (8.0 gm., 37% yield collected at 97-98°/2.5 mm., n^® 1.4738. The infra red spectrum of the distillate Indicated that cyclodecanone

(< l°fa) and cyclodecanone methyl enol ether (14.4^) were present. The concentration of the enol ether was deter mined as follows. Several solutions (in cyclohexane) of known concentration of pure cyclodecanone methyl enol ether

(vide infra) were prepared and their optical densities measured in the infra-red at 5.92^/x. A solution (in cyclo hexane) of known concentration of the impure ketal was then prepared and the optical density at 5 -92yUL measured.

This optical density was compared with the calibrated opti cal densities; calculations showed that the enol ether content of the impure dimethyl ketal was 14.4 lo.3$.

A number of attempts were made to produce pure cyclodecanone dimethyl ketal. They all failed because 98 the ketal eliminates alcohol so readily. The distilled ketal-enol ether mixture appeared to be stable when stored at -20°.

Cyclodecanone methyl enol ether was prepared as follows. Cyclodecanone (9.0 gm. , 0.0584 mole), trimethyl orthoformate (6.5 gm., 0.0613 mole, 5% excess), and abso lute methanol (20.0 gm.) were mixed and the methanolic hydrogen bromide catalyst was added. After heating the mixture gently for 15 minutes, its infra-red. spectrum showed that all of the ketone had reacted. The solution was refluxed for one hour and enough solid potassium car bonate was added to neutralize the acid catalyst. Dis tillation gave 7.5 gms. of enol ether contaminated with a trace of ketal (b.p. 7?°/3.5 mm., 77^ yield). This material was chromatographed through alumina* (activity one, 150 gm.) and eluted with tiwo liters of petroleum ether

Aluminum oxide, "Woelm," M. Woelm, Eschwege, Germany.

(dried over calcium hydride, b.r. 30-60°). Distillation gave 5*3 gm., 55% yield, of pure cyclodecanone methyl enol ether, b.p. 55°/2 mm., n^° 1.4875.*

■» These ketals can be quantitatively converted to their corresponding enol ethers by chromatography through alumina. Even 'neutral' alumina is sufficiently active 99 to effect this reaction. If the alumina is not completely dry, considerable amounts of ketone may also be produced.

2,2,4,4-Tetramethylcyclobutanone dimethyl ketal

could only be prepared by refluxing the alcohol-ketone- orthof orma.te solution for 24 hours.

The cyclobutanone dilsopropyl ketal was contamin ated with approximately 50$ trilsopropyl orthoformate.

These two compounds could not be separated by vacuum dis tillation (24-inch column), vapor-phase chromatography

(decomposition), or by liquid-phase chromatography (enol ether formed). The boiling point of the orthoformate is almost identical with the (estimated) boiling point of the pure ketal.

The cyclotetradecanone dimethyl ketal is a solid and precipitates from the reaction solution. This ketal was recrystallized once from absolute methanol and then vacuum sublimed. Both cyclodecanone dimethyl ketal, and its enol ether, hydrolyze to cyclodecanone in at least 94.4$ and

93.8$ yields, respectively. This was determined by hydro lyzing these compounds under conditions of the kinetics, and then converting the ketone formed to its semicarba- «- zone.

* Carbonium ions, generated on these medium-size rings, are known to undergo trsnsannular reactions: V. Prelog Angew. Chem., £0, 145 (1958). 100

2,2,4,4-tetramethyl-3-oxetanone: 0

was prepared, m.p. 42.5-44.5°; b.p. 117.5-119.0°; carbonly

frequency lnfra.-red 5.55^5 ultraviolet X max. 297.5 nyU,

£ max. 21.2 (In kinetic solvent). Lit. (70)» m.p. 48°,

b.p. 116-120°, carbonyl frequency infra-red 5 .^m *

(70) B. L. Murr, G. B. Hoey, and C. T. Lester, J. Am. Chem. Soc.,£2., ^ 3 0 (1955).

Attempts to prepare the corresponding dimethyl ketal all

met with failure. A solution of the ketone, methyl alco

hol, an excess of trimethyl orthoformate, and acid cat

alyst were left standing for eight weeks at 30-40°. No perceptible decrease in the ketone carbonyl frequency (in

fra-red) of the ketone in the solution was noted. Reflux-

ing (64°) for eight days did not cause any reaction to

occur either. A small sample of this solution was placed

In a sealed tube and heated at 150° for 3 hours. Subse

quent infra-red analysis indicated that an estimated 30%

of the ketone had not reacted, another 30% had suffered

ring fissure (carbonyl band at and the rest was

unaccounted for. The reason for this peculiar behavior

is not clear. APPENDIX A

Figures 7 through 15

101 1 0 2

I. Cyclobutanone diisopropyl ketal 2. Cyclobutanone diethyl ketal 0 3. Cyclobutanone dimethyl ketal 4. 2,2,4,4 -Tetramethylcyclobutanone dimethyl ketal (+5 In units)

MeO OMe -3

- 4

MeO OMe Me^ Me -5 M e' Me

-6 EtO OEf

- 7

iprO Oipr

-8

j. x .i_ 3.30 3.40 3.50 3.60 3.70

Figure Activation Energy Plots 103

l Cyclopentanone dimethyl ketal 2 Cyclopentanone diethyl ketal 3 Cyclopentanone diisopropyl ketal 4 3,3 - Dimef hylcyclopentanone dimethyl ketal 5 2 -Methylcyclopentanone dimethyl ketal

iprO Oipr

-2 EtO OEt

/ - 3 MeO OMe Me , Me

3 . 5 3 . 6 3.7 3 . 8 4 . 0

Figure 8® Activation Energy Plots. 10U

1. Cyclohexanone dimethyl ketal 2. Cyclohexanone diethyl ketal 3. Cyclohexanone diisopropyl ketal 4. 3,3 ~ Dimethylcyclohexanone dimethyl ketal 5. 3,3,5,5— Tetramethylcyclohexanone dimethy! ketal 6. 2-Methylcyclohexanone dimethyl ketal ( + 1 In unit)

+ 2

MeO OMe Me

-2 MeO Me

EtO.

MeO ^ OM

-Me Me Me -4 Me

34 35 3 7 3 8 3.9

Figure9. Activation Energy Plots 105

I. Cycloheptanone dimethyl ketal +2 2. Cyclooctanone dimethyl ketal 3. Cyclononanone dimethyl ketal 4. Cyclodecanone dimethyl ketal 5 Cyclododecanone dimethyl ketal 6. Cyclotetradecanone dimethyl ketal

MeO OMe *2 MeO OM. T -2

MeO OMe

-3 MeO 0M(

OMe MeO OMe -4 -I-OMe

-5

3.4 3.5 3.7 383.6 3.9

Y x ,C)3

Figure 10 .Activat ion Parameter Plots 106

1. Cyclodecanone methyl enol ether 2. Di-n-propyl ketone dimethyl ketal 3. Di-n-hexyl ketone dimethyl ketal

(n- pr)2 C(OMe) -2

- 4 c (n-hexyl)2 C(OMe)

- 5 OMe

-6

-7

3.3 3.4 3.5 3.6 3.7

Figure 11,. Activation Parameter Plots 107

Cond i t ions: Temperature 793° 2.8 Ketal conc. 0.669 gm./iOO ml. soln. Acid conc. 2.43 x I0~4 moles HCl/l. soln.

2.4 / 9 2 % com pletion

2.0

0.8

0 .4

510 15 20 2 5 Time (min.)

Figure 12, Acid — Catalyzed Hydrolysis of Cycloheptanone Dimethyl Ketal (Run 174). 1 0 8

Gond itions : Temperature 28.12° Ketai conc. 0.598 gm./lOO ml. soln. 2.4 Acid conc. 2.40 x I0'4 moles HCI/l. soln. k i = 0.0704 min.-1

2.0

86% completion

< I 8

0.8

0.4

24 30 Time (min. )

Figure 13. Acid - Catalyzed Hydrolysis of Cyclobutanone Diisopropyl Ketal (Run 43). 109

Gond itions : Temperature 15.31° Ketal conc 0 . 6 5 3 gm./lOOml. soln Acid conc. 1.021 x I0'3 moles HCl/l. soin.

k, = 0.02 565 min'1 k~ = 25.1 I. /m. - min. 69% completion

1.0

^ 0.8

< 0.6

0.4

0.2 -

0 10 20 30 4 0 50 Time (min.)

Figure Acid - Catalyzed Hydrolysis of Cyclohexanone Dimethyl Ketal (Run 112). 110

61% completion

0.8

0.7

0.6

0.5'

0.4 Conditions: Temperature 0.00° Ketal conc. 0.525 gm./lOO ml. soln. Acid conc. 1.04 x I0~z moles HCl/l. soln. 0.3 0 . 0 0 1 0 9 0 min.

O 200 400 600 800 1000 Time (min.)

Figure 15® Acid - Catalyzed Hydrolysis of Cyclodecane Methyl Enol Ether (Run 233). APPENDIX B

Infrared Spectra of Ketals

111 joa.

CYCLOBUTANONE DIMETHYL KETAL ICH:

OCH

CYCLOBUTANONE DIETHYL KETAL CYCLOBUTANONE DJISOPROPYL KETAL

n a

2,2,4,4 -TETRAMETHYLCYCLO- BlITANONE DIMETHYL KETAL H,CO OCH: CYCLOPENTANONE DIMETHYL KETAL

x t

CYCLOPENTANONE DIETHYL KETAL : .0CH2CH3 f__pOCH2CH3 CYCLOPENTANONE DIISOPROPYL KETAL ^ s ^OCH:(CHJ)s f POCHiCH,),

2-METHYLCYCLOPENTANONE DIMETHYL KETAL 3,3 - DIMETHYLGYdLOPENTANONE DIMETHYL KETAL

CYCLOHEXANONE ;DIMETHYL KETAL cyclohexanone diethyl ketAl ^ £ ch2ch3 f T^QCH2CH3

CYCLOHEXANONE 01 isopropyl ketaC I

2-METHYLCYCLOHEXANONE DIMETHYL KETAL

4 3,3 “DIMETHYLGYCL(j)HEXANONE j DIMETHYL KEjTAL

oo 3,3,5,5-TETRAMETHYLCYCLOHEX- ANONE DIMETHYL KETAL

HjC CH,

CYCLOHEPTANONE DIMETHYL KETAL ,OCH2 'OCH jsa. to

- CYCLOOCTANONE lilMETHYL KETAL

[ rociH3

CYCLONONANONE DIMETHYL KETAL 85.6% CYCLODECANONE DIMETHYL KETAL + 14.4% CYCLODECANONE METHYL ENOL ETHER

HjCO OCHj OCH3

CYaODODECANONE Dl METHYL KETAL 1fig » £ .

GYCLQTETRADECANONE DIMETHYL KETAL (SOLID)

r ^ ^ V ° CH3 C ^ > ch*

JSft

Dl-N-PROPYL KETONE DIMETHYL KETAL

.OCH;

*OCH:

r*> r-> i o o : w © 1CO 1 1C <3 " i ■ 100 *9 1 i 1 i t 1 [ ! 1 . 9 0 3 1 »s - o -- 99 9 9 9 ! «... . i . \ — j— 7 H 4 - h r r 8> B O i B J /• t0 r a n ! i i i1 r \ / - — — r - - 4 \ i V J V l 7» 1 / r 4 3 i \ - j . - . .... / r - -- \ j « fl3 i \ o ; j j I j j i ! — r ... 1 ! ! i i 5O B 3 ; 1 a j <3 i .' i j ; i \ — -- .. —-; .. - i 1 ! ] / i 4 3 3 1 } 3 DI-N-HEXYL KETONE DIMETHYL ! V KETAL ; i 3n 3 0 ; ! o | i-- Ik J 4 - CH3(CH2)5 och3 ; t r 2 0 2 o i 2 3 3 i -- CH3(CH2)5/ och3 -— — - > > ! ; ) 3 ; 1 i . 1 . J 1— 1 ' .. i ■ 1 i . i 1 i " i 9 i .... 9. ; 1 i S 1 I c !

CYCLODECANONE METHYL ENOL ETHER

C J " " 1 CYCLOHEXANONE METHYL ENOL ETHER

.OCH-

2,2,4,4- TETRAMETHYLCYCLO BUTANONE

CH, .CH,

CH, 'CH APPENDIX C

Tables: Numerical Data

125 126

TABLE 23

Compound Di-n-propyl Ketone Dimethyl Ketal

Temp. 15.86° Date 4-10-58 Acid. conc. 4.88xl0~^ (moles/1.)

Run 1 Run 2 Run 3

Ketal conc. 0.375 Ketal conc. 0.365 Ketal conc. 0.446 (gms./lOO mis.) (gms./lOO mis.) (gms./lOO mis.) Calc. Aq =0.005 Calc. AQ = a 005 Calc. Aq = C4006

Time A+ In A q S z A sl Time A^ In iLQ.fe~Ao. Time A. In k > s r A o (min.) Aoo“At (min.) Aoo”At (min.) A v o ~ M >

3 0.109 0.211 3 0.105 0.202 3 0.133 0.219 6 0.193 0.421 6 0.185 0.411 7 0.252 0.476 9 0.255 0.651 9 0.250 0.615 9 0.305 0.620 12 0.308 0.310 12 0.304 0.820 12 0.366 0.313 15 0.366 1.085 15 0.344 1.01 15 0.419 1.02 18 0.393 1.24 18 0.378 1.20 18 0.459 1.205 21 0.418 1.42 21 0.403 1.37 21 0.490 1.38 24 0.441 1.61 24.1 0.430 1.59 24 0.520 1.58 27 0.460 1.80 27 -- 27 0.558 1.92 00 0.551 — 00 0.539 — 00 0.655 - 00 0.549 — 00 0.538 - 00 0.652 -

00 0.550 Loo 0.539 ^00 = 0.653 11 \ = 1.615 *1 = 1.585 1.585 24 24 24 . -1 » 0.0672 min.-1 = O0O66O min. ^ = 0.660 min. k2 = 137.7 l./m.min. k2 = 135.4 lo/m .min. k„ = 135.4 l./m.min 1 2 7

T A B L E 2 4

Compound Di-n-propyl Ketone Dimethyl Ketal

Temp. 7.83° Date 4-12-58 Acid conc. 9«31xlcHf (moles/l.)

Run 4 Run 5 Run 6

Ketal conc. 0.400 Ketal conc. 0.481 Ketal conc. 0.439 (gms./lOO mis.) (gms./lOO mis.) (gms./lOO mis.) Calc. A0 = 0.005 Calc. A0 = 0.006 Calc. Ac = 0.006

Time A+ In Time iL In -A02^ 0 —A© ° rp,*„„Time A. A In 1 _ A0 0 —A0 (min.) J^)0 At (min,) (min.) Aoo~At

3 0.084 0.142 3 0.094 0,131 3 0.087 0.135 7 0.166 0.318 6 0.180 0.278 6 0.155 0.262 9 0.203 0.409 9 0.244 0.405 9 0.220 O .405 12 0.254 0.548 12 0.306 0.542 12 0.274 0.540 15 0.295 0.676 15 0.354 0.664 15 0.316 0.658 18 0.336 0,819 18 0.402 0.801 18.7 0.372 0.840 21 0.363 0.932 21 0.440 0.926 21 0.393 0.919 24 0.391 1.06 24 0.473 1.05 24 0.428 1.065 27 0.419 1.205 27 0.505 1.19 27 0.452 1.18 oo 0.595 — oo 0.725 — oo 0.650 oo 0.596 — oo 0 .72?- oo 0.649 -

Aq o = 0.596 Aoo = 0.724 Aq o - 0.650

kl = 1.07 ki = 1.062 kl = 1.063 24 24 24

ss 0.04455 min.-"*" 0*0443 min. ^ = 0.443 min.-^

k g = 47.9 l . / m . m i n k g = 47.6 l./m.min. kg = 47.6 l . / m . m i n . 1 2 8

T A B L E 2 5

Compound Di-n-propyl Ketone Dimethyl Ketal

Temp. -0.02° Date 4-14-58 Acid conc. 2 .072x10“' (moles/l.)

Run 7 Run 8 Run 9

Ketal conc. 0.261 Ketal conc. 0.300 Ketal conc. 0.295 (gms ./100 mis.) (gms./lOO mis.) (gms./lOO mis.) Calc. A0 = 0*003 Calc. A0 = 0.004 Calc. A0 = 0.004

Time a+ In j o o - A o Tim* At In A do-Ao Ti mfl A-f. In Aoo—Ao (min,) Aqo— (min.) Aocr-At (min.) ^oo“^t

5 0.071 0.191 5 0.076 0.178 5 0.089 0.217 10 0.116 0.344 10 0.133 0.340 10.5 0.136 0.361 15 0.158 0.510 15 0.186 0.525 15 0.178 0.510 20 0.196 0.688 20 0.223 0.675 20 0,222 0.690 26 0.234 0.904 25 0.256 0.833 25 0.254 0,850 30 0.248 1.00 30 0.291 1.035 30 0.282 1 *0 1 - 35 0.271 1.17 35 0.312 1.17 35 0.307 1.185 40 0.288 1.33 40 0.332 1.33 40 0.327 1.345 45 0.307 1.53 45 0.353 1.525 45 0.350 1.57 00 0,391 — 00 0.450 — 00 0.440 * 0 0 0,391 — 00 0.450 - 00 0.441 - 11 > 0.391 0.450

0 0.441 0 A o o ® A do =

1! 11 1.350 & 1 * ^ 5 & 1*355 kl = 40 40 40

— 0.0336 min.-1 ss 0.0338inin. 1 ss 0.3375 min.-1

= 16.25 l./m.min. 1^2 = 16.36 l./m.min. k 2 = 16.29 l./m.min* 1 2 9

T A B L E 2 6

Compound Di-n-hexyl Ketone Dimethyl Ketal

Temp* 0*00° Date 7-17-58 Acid conc. 1 .0 4 0 x1 0“^ (moles/l,)

Run 10 Run 11 Run 12

Ketal conc. 0.311 Ketal conc* 0,295 Ketal conc. 0.278 (gms./lOO mis.) (gms*/l00 mis.) (gms./lOO mis.) C ale. A q = 0 * 003 Calc, A0 = 0.003 Calc. A q = 0.003

Time At In ^ o o - ^ Time At In A o o - A o Time At In A°0-A° (min.) &o o ~ M , (min.) A0o“4t (min.) Aoo-At

5 0.055 0.165 5 0.051 0.160 5 0.049 0.161 10 0.085 0.277 10 0.085 0.293 10 0.080 0.285 15 0.118 0.412 15 0.112 0.409 15 0.108 0.415 20 0.145 0.540 20 0.145 0.579 20 0.131 0.536 25 0.172 0.688 25 0.163 0.683 25 0.153 0.666 30 0.193 0.818 30 0.185 0.829 30 0.173 0.798 35 0.209 0.931 35 0.203 0,967 35 0.193 0.955 40 0.229 1.092 40 0.218 1.095 40 0.206 1.07 46 0.245 1.245 45 0.231 1,225 45 0.218 1.19 oo 0.343 _ 00 0.326 — 00 0*311 — oo O .342 — 00 0.326 - 00 0,312 — «*P 11 11 o 0.343 0 0.326 "ooA = 0.312 kl = 1.092 kl = I.O95 kl = 1.07 40 40 40

= 0.0273 min."1 = 0.02735 min.-1 = 0.0267 min*-1 k2 = 2.625 l./m.min. k2 = 2.63 l./m.min* k 2 = 2.57 lo/m.roin, 130

T A B L E 2 7

Compound Cyclobutanone Dimethyl Ketal

Temp* 15*32° Date 3-20-58 Acid conc. 1 .022xl0“2 (moles/l.)

Run 13 Run 14 Run 15

Ketal conc* 0*357 Ketal conc* 0*364 Ketal conc. 0.402 (gms./lOO mis*) (gms./lOO mis.) (gms./lOO mis.) Calc. A0 = 0.009 Calc. A q = 0.10 Calc* A q = 0*011

Time At In Aoo-Ao Tims In &OO—&Q T i ^t Tn A0 0 - A o (min.) Aoo-At (min.) Aoo-At (min.) Aoo-At

20 0.066 0.102 20 0.065 0.109 20 0.075 0.1045 40 0.112 0.193 40 0.110 0.191 35.2 0.114 0,174 60 0.157 0.291 55 0.142 0.254 60 0.172 0.284 80 0*199 0.391 80 0.196 0.382 80 0.217 0.380 100 0.232 0.478 100 0.239 0.495 100 0.256 0.471 120 0.264 0.570 120 0.263 0.565 120 0.289 0.556 140 0.294 0,665 140 0.295 0,665 140 0.323 O.651 160 0.319 0.748 160 0.318 0.745 160 0.352 0.740 180. 0.341 0.831 180 0.340 0.826 180 0.378 0.829 oo 0.598 — 00 0.602 — 00 0*662 — oo 0*595 - 00 0.600 — 00 0.659 11 > 0.597 0.601 0.661 o o Aoo = -^00 =

kl = 0.757 kl = O.75O kl = O .745 160 160 160

= 0.004735 min.-1 = O.OO469 min.*”1 = 0.004655 min.“: 11 k 2 = 0.463 l./m.min. k2 " 0o459 l./m.min. OJ 0.456 l./m.min 1 3 1

T A B L E 2 8

Compound Cyclobutanone Dimethyl Ketal

Temp* 28*12° Date 3-20-58 Acid conc. l.OlOxlO-2 (moles/l*)

Run 16 Run 17 Run 18

Ketal conc. 0*375 Ketal conc. 0,391 Ketal conc. 0.444 (gms*/l00 mis.) (gms./lOO mis.) (gms./lOO mis.) Calc. Aq = 0.010 Calc. Aq = 0.010 Calc. A0 = 0.012

In Ao 0_Ao In Ao o -Ao In Aoo—A Time At Time At Time At [min.) Aq o —At (min.) Aoo-At (min.) Aoo-A

5 0.105 0.169 5 0.114 0.178 5 0.133 0.185 10 0*175 0.315 11 0.191 0.333 10 0.196 0.299 15 0.236 0.464 15 0.247 0.464 15 0.273 0.455 20 0.284 0.596 20 0.295 0.588 20 0.329 0.585 25 0.331 0.747 26 0.352 0.766 25 0.384 0.732 30 0.364 0.866 30 0.383 0.871 30 0.425 0.860 35 0.392 0.980 35 0.408 0.970 35 0.454 0.958 40 0.435 1.19 40 0.452 1.17 38 0.493 1.115 45 0.458 1.32 45 0.472 1.275 45 0.539 1.33 oo 0.621 — 00 0.651 — 00 0.727 — oo 0.621 - 00 O.65I - 00 0.729 - II o n 0,621 ^ O .728

0 0.651 0 Aoo ~ 1.18 kl = kl = 1.15 kl “ 1.165 40 40 40

= 0.0295 min."1 = 0.02875 min."1 = 0.0291 min."1

k 2 = 2.925 l./m.min. k2 = 2.845 l./m.min. k 2 = 2«885 l./m.min 1 3 2

T A B L E 2 9

Compound Cyclobutanone Dimethyl Ketal

Temp. 7 . $ 3 ° Date 3-25-53 Acid conc.l.03Ljcl0“ 2 (moles/l.)

Run 19 Run 20 Run 21

Ketal conc. 0,363 Ketal conc. 0.442 Ketal conc. 0.463 (gms./lOO mis.) (gms./lOO mis,) (gms./lOO mis.) Calc. Aq — 0,010 Calc. Aq = 0.012 Calc, Aq = 0.012

Time At In A00-Ap Time At In Apq-A<> Time At In Aoo-Ao [min,) A00_At (min.) Aoo-At (min.) Aoo—At

90 0.090 0.145 90 0.102 0.141 90 0.108 0.138 180 0.151 0.272 180 0.176 0.274 180 0.190 0.272 280 0.218 0.432 275 0.246 0.419 272 0.266 0.416 360 0.260 0.576 360 0.298 0.536 360 0.320 0.530 450 0.302 0.678 450 0.350 0.675 450 0.382 0.683 546 0.339 0.806 542 0.390 0.798 540 0.422 0.793 630 0.370 0.931 630 0.430 0.935 —— 720 0.400 1.07 720 0.461 1.06 720 0.498 1.05 810 0.430 1.225 — —— 810 0.531 1.185 oo 0.604 — 00 0.700 — 00 0.761 — oo 0.603 - 00 0.700 — 00 0.758 -

Aq o ~ 0.604 Aq o « 0.700 Aoo = 0.760

kl = 1*195 ki = 1.105 ki = 1.17 800 800 800

0.001495 min."1 = 0.00148 min."1 = 0,001463 min."1

k2 * 0.145 l./m.min. k2 = 0,1435 l./m.min. k2 = 0.1418 l./m.min. 1 3 3

T A B L E 3 0

Compound Cyclobutanone Diethyl Ketal

Temp* 15.32° Date 3-20-58 Acid conc. 1.022xL0“^ (moles/l.)

Run 25 Run 26 Run 27

Ketal conc* 0*535 Ketal conc* 0.48? Ketal conc. 0.443 (gms./lOO mis.) (gms./lOO mis.) (gms./lOO mis.) Calc. Aq = 0.011 Calc. AQ = 0.010 Calc. AQ = 0.009

Time A*. In Apo-Ap Time At In App-Ap Time At In App-Ap (min.) Aoo-At (min.) -^oo-At (min.) A00_Jit

5 0.071 0.095 6 0.075 0*112 5 0.063 0,100 11 0*138 0.209 11 0.127 0.211 10 0.109 0,191 15 0.177 0.285 . 16 0.172 0.304 15 0.151 0.284 21 0.232 0.399 21 0.213 0.399 21 0.199 0.402 25 0.260 0.460 27 0.256 0.507 25 0.225 0.472 30 0.299 0.560 31 0.289 0.599 30 0.257 0.568 36 0.339 0.668 37 0.323 0.703 35 0.284 0.652 . 40 0.361 0.732 41 0.338 0.751 40 0.313 0.756 45 0,386 0.812 46 0.366 0.852 45 0.332 0.829 00 0.682 — 00 0.630 - 00 0.580 — 00 0.687 - 00 0.632 - 00 0.584 -

00 = 0.685 Aoo = 0.631 Aoo = 0.582

1 “ O .737 kl “ 0.745 kl * 0.752 40 40 40

= 0.01842 min.“- S3 0.01365 min.“^- — 0.01882 min.”^

= 1.805 l./m.min = 1.827 l./m.min = 1.843 l./m.min. 1 3 4

T A B L E 3 1

Compound. Cyclobutanone Diethyl Ketal

Tenyp. 28*12° Date 3-22-58 Acid conc, 2,015x10”^ (moles/l*)

Run 28 Run 29 Run 30

Ketal conc* 0.429 Ketal conc. 0*406 Ketal conc, 0,371 (gms./lOO mis.) (gms./lOO mis*) (gms./lOO mlso) Calc. Aq = 0,009 Calc, Aq * 0.009 C ale« Aq = 0 * 008

Time A^ In ^R2~^P. Time A+ In Aoo-Ao Time Af. In Ao°-Ao (min.) Aoo-At (min.) -^oo-^t (min.) A00-At

/S a / A 5 0.070 0.118 5 0.066 0.113 5 O.uo^ O.lkil 10 0.121 0.226 10 0.115 0.223 10 0.111 0.241 15 0.163 0.326 16 0.163 0.344 15 0.146 0.337 20 0.203 0.432 20 0.191 0.422 20 0.178 0.435 25 0.239 0,536 25 0.224 0.521 25 0.214 0.554 30 0.272 0.645 30 0.261 0.648 30 0.247 0.683 35 0.302 0.752 35 0.289 0.751 35 0.270 0.782 40 0.326 0.850 40 0.309 0.836 40 0.289 0.871 45 0.354 0.975 45 0.335 0.958 45 0.311 0.988 00 0.563 — 00 0.538 — 00 0,490 — 00 O.563 — 00 0,538 - 00 0.491 - •a; 11 11 0 0 0.563 Aoo = 0.538 0 0.491 JT II 0.850 0.850 1 kl = kl - 0.878 40 40 40

0.02125 min.-1 — 0,02125 min,”1 — 0.0220 min.*"^

k 2 = 10*54 l./m»min. kg =■ 10.54 l./m.min. “2 = 10.92 l . / m . m i n . 1 3 5

T A B L E 3 2

Compound Cyclobutanone Diethyl Ketal

Tempe 7.83° Date 3-24-58 Acid, conc* 1.031x10“^ (moles/l,)

Run 31 Run 32 Run 33

Ketal conc, 0,466 Ket&l conc, 0,406 Ketal conc, 0.417 (gms./lOO mis,) (gms/lOO mis.) (gms./lOO mis,) Calc. Aq = 0,010 Calc. AQ = 0,009 Calc. AQ = 0.009

Time At In o-fo Time At In ^ o o - * o Time At In Adq—Aq (man,) Ajo-Ai (rain,) ^oo-^t (min,) Auo-At

30 0 , U 5 0,191 >~on 0,115 0.719 '■s r\ 0,102 0.139 60 0l214 0.412 60 0 .201- 0.441 60 0.186 0.398 90 0,269 0,565 90 0.240 O.56O —— — 120 0.333 0.772 120 0.298 0.765 121 0.294 0.751 150 0.375 0.936 150 0,330 0.902 150 0.332 0.912 ISO 0.428 1.19 180 0.364 1.07 ISO 0.365 1.075 210 0.4-51 1.325 210 0.400 1.29 210 0.400 1.29 240 0.478 1.51 240 0.423 1.455 240 0.422 1.4-5 270 0.492 1.62 270 0.440 1.60 270 0,440 1.60 00 0.612 — 00 0.548 - 00 0.548 — 00 0.610 - 00 0.550 - 00 0 . ^ 0 - A : 0.611 "00 = Aco = 0.549 A c o ~ 0.549 kn = 1.52 kl = 1.445 kl - 1.45 240 240 240

= 0.00633 rain»”k = 0.00602 min.-'*' = 0.00604 min.”^

k2 = 0,614 l./m.min. kp = 0.584 l./m.min. k2 = 0.585 l./m.min. 136

T A B L E 3 3

Compound Cyclobutanone Diisopropyl Ketal

Temp* 15o86° Date 5-17-58 Acid conc. 4 .61x10“^ (moles/l.)

Run 37 Run 38

Ketal conc* 0,462 Ketal conc. 0.402 (gms./lOO mis.) (gms./lOO mis.) Calc, AQ = 0,014 Calc. A0 = 0.014

Time A+ In tpo-A o Time At In " A Ax (min.) Aoo-"t (min,) A0o~At

r\ n m A r ✓C | J. 5.i> 0.056 0.207 10 0.092 0.337 10 0.084 0.365 15 0.123 0.514 15 0.106 0.507 20 0.150 0.693 20 0.128 0.677 25 0,166 0.820 25 0.146 0.836 30 0.187 1.01 30 0.163 1.02 35 0.208 1.25 35 0.175 1.17 40 0.212 1.30 40 0,189 1.385 45 0.228 1.545 45 0.197 1.53 oo 0.286 oo 0.248 — oo 0.286 - oo 0.248 -

A00 == 0.286 Aoo == 0.248

k -• 1.37 kl == 1-355 40 40

= 0.03425 min.“^" = 0.0339

k2 = 74.3 l./m.niino k2 = 73,5 l./m.min. 1 3 7

T A B L E 3 4

Compound Cyclobutanone Diisopropyl Ketal

Temp* -0*04° Date 5-20-58 Acid conc. 5.19xLO~3 (mole s/l.)

Run 39 Run 40

Ketal conc. 0*623 Ketal conc. 0*635 (gms./lOO mis*) (gms ./l00 mis*) Calc, = 0.019 Calc * Aq — 0*020

Aq o —4© n ik&rCc Time A . ^ Time (min.) (min.) At 111 W 4 i

3 0*066 0.140 0.071 0.109 6 0*110 0.293 6 0.115 0.289 9 0.154 0.470 9 0.147 0.412 12 0.181 0.600 12 0.185 0.574 15 0*217 0.797 15 0.219 0.747 18 0*228 0.866 18 0.234 0.837 21.5 0*250 1.025 21 0.257 0.990 24 0,269 1.185 24 0.276 1.135 27 0,283 1.32 27 0.292 1.27 o o 0*379 — CO 0.398 — o o 0.379 — 00 0.398 -

A o o = 0*379 A d o == 0.398

kl = 1.17 kl =* 1 -W. 24 24 0 CO CO 0

• -1 = min.-^ = 0.0472 nuLii*

9.41 1 ,/m.min. : 9.10 1 ./m.min, k 2 - k2 = 1 3 8

T A B L E 3 5

Compound Cyclobutanone Diisopropyl Ketal

Temp* 2 8 d 2 c Date 5-21-58 Acid conc. 2.40x10“^ (moles/l.)

Run 41 Run 42 Run 43

Ketal conc. 0.594 Ketal conc. 0.543 Ketal conc. 0.598 (gmsa/100 mlso) (gms./lOO mis.) (gms./lOO mis.) Calc. A q - 0,018 Calc. Ac = 0.017 Calc. AQ = 0.017

Time A, In •Hoo-A> Time iL In Aoo~A° Time A, In ^ ° -*<> (min.) Aoo-^t (min.) A q o - A t (min.) A00_A-t

0,090 0*231 3« 5 0.094 A Air*/A 3 0.08b 0.219 6 0.143 0.444 6 0,130 0.439 6 0.141 0.439 9 0.182 0.637 9 0.168 0.648 9 0.184 0.647 12 0*218 0.855 12 0.200 0.859 12 0,218 0.855 15 0.246 1.065 15 0.224 1.055 15 0.246 1.065 18. 0,268 1.27 18 0.245 1.26 18 0.268 1.265 21 0.287 1.48 21 0.263 1.485 21 0.287 1.485 24 0.300 1.66 24 0.275 1.67 24 0.301 1.68 27 0.312 1.86 27 0.287 1.89 27 0.315 1.92 oo 0.365 - 00 0,335 - 99 0.366 _ oo 0.366 - 00 <>•#?. - OO 0.366 - «s° 11

= 0.366 0 Aoo 0.335 Aoo == 0.366

kl ■= 1.67 kl = 1.68 kl == 1.69 24 24 24

: 0.0696 min.”'*' = 0.0700 man.• -1 = 0.0704 .rain."^

k 2 = 290 1,/m.min. k 2 = 292 1 ./m.min. k2 = 293 1 ./m.mir 1 3 9

T A B L E 3 6

Compound 2,2,4,4-Tetramethcyclobutanone Dimethyl Ketal

Temp, 15.86° Date 7-3-58 Acid conc. 1.023x10“2 (moles/l.)

Run 261 Run 262 Run 263

Ketal conc. 0.390 Ketal conc. 0.490 Ketal conc, 0.515 (gms./lOO mis.) (gms,/l00 mis.) (gms./lOO mis.) Calc. A0 =» 0.008 Calc. A0 = 0.011 Calc. Ap = 0.011

In Aq o -Aq Time At In p:9°r^9 Time At In jSSrfe Time At (min.) Aoo-At (min.) W ^ t (min,) Aoo-At

60 0.063 0.068 60 0.081 0.106 60 0.088 0.113 120 0.115 0.174 120 0.145 0.214 120 0.150 0.211 180 0.164 0.289 180 0.204 0.322 182 0.219 0.337 246 0.209 0.402 240 0.257 0.435 240 0,265 0.426 300 0.245 0.507 300 0.306 0.548 300 0.323 0,556 360 0.282 0.626 360 0.346 0.653 365 0.358 0.645 418 0.307 0.718 420 0.378 0.743 424 0.401 0.763 480 0.335 0.828 480 0.421 0.885 486 0.437 0.875 540 0.359 0.936 540 0.450 0.990 540 0.461 0,955 00 0.571 — 00 0.712 — 00 0.741 — 00 0.57^ — 00 0.712 - 00 0.741 - II ^

O = 0.573 = 0.712 0 Aoo = Aoo = 0.741 = 0.870 kl = kl == 0.912 k! = 0.905 478 500 500

= 0,00182 Jiiin.-^ = 0.001822 min.“^ = 0.001810 min.-^

k2 = 0.1780 l./m.min. k2 = 0.1783 l./ijurain. k2 = 0.1770 l./m.min 140

T A B L E 3 7

Compound 2,2,4,4-Tetramethylcyclobutanone Dimethyl Ketal

Temp. 28.12° Date 7-6-58 Acid conc. 1.010x10”^ (moles/l.)

Run 264 Run 265 Run 266

Ketal conc. 0.503 Ketal conc. 0.487 Ketal conc. 0.515 (gms./lOO mis.) (gms./lOO mis.) (gms./lOO mis.' '■'ale. A0 = 0.011 Calc. A0 = 0.011 Calc. Aq = 0.011

Time A+ In ^0-4o Time A^ In A>o-A> Time A+ In A o o - ^ o (min.) -^oo-^t (min.) Aoo-At (min.) &o o - M >

-1 A 10 0.07? 0.095 *1 A \Sr\ « uuv Uixuifr\ ~i r\! *L\J \sA • AS'✓0*4' j VA O 1J.V^ A! 20 0ll40 0.199 20 0.139 0.203 20 0.147 0.199 30 0.197 0.300 30 0.196 0.306 30 0.207 0.300 40 0.247 0.399 40 0 .24.8 0.411 40 0.261 0.402 50 0.294 0.501 50 0.286 0.498 50 0.309 0.501 60 0.334 0.596 60 0.323 0.591 50 0.350 0.593 70 0.371 0.693 70 0.362 0.693 70 0.383 0.678 80 0.406 0.796 80 0.395 0.792 ,fc«80 0.421 0.785 90 0.437 0.895 90 0.427 0.900 ’ 90 0.461 0.909 00 0.731 — 00 0.713 — 00 0.765 00 O .727 — 00 0.711 • - 00 O .767 -

= 0.730 A : 0.712 ^ 0 0 = OO ^■00 = 0.766 ^ - * 0.794- 0.802 ■ P.797 ‘‘i ■ klJL = 80 80 80

= 0.00997 min.-'*' : 0.00992 min.• -1 = 0.01002 min. J 11 = 0.988 1 ,./m.min. . 0.982 1 ,,/m.min. CM k2 = k 2 ’ 0.993 1.,/m.mix 1 4 1

T A B L E 3 8

Compound 2,2,4j4-Tetramethylcyclobutanone Dimethyl Ketal

Temp. 0.00° Date 7-7-58 n.cid conc. 1.040x10“^ (moles/l.)

Run 267 Run 268 Run 269

Ketal conc. 0.524 Ketal conc. 0.572 Ketal conc. 0.455 (gms./lOO mis.) (gms./lOO mis.) (gms./lOO mis.) Calc. Aq = 0.011 Calc. Aq = 0.012 Calc. Aq = 0.010

Time A^. In ^2Pr:^2. Time A^ in Time In (min.) Aoo-4t (min.) Aoo—H-t (min.) Aoo-At

720 0.097 0.118 720 0.102 0.114 720 0.077 0.105 1440 0.156 0.23*1 I44.O 0,180 0.223 1440 0.126 0.191 2220 0.220 0.322 2220 0,222 0.289 2220 0.184 0.304 2880 0.263 0.402 2880 0.304 0.429 2880 0.253 0.454 3600 0.337 0.560 3600 0.369 0.556 3600 0.304 0.582 4320 0.387 0.680 4320 0.422 0.672 4320 0.313 0.604 5040 0.430 0.800 5040 O .465 0.780 5040 0.368 0.770 6480 0.498 . 0.985 6480 0.548 1.025 648O 0.424 0.968 7930 0.555 1.255 7930 0.608 1.25 7930 0.492 1.28 00 0.772 - 00 0.847 - 00 0.676 — 00 0.771 — 00 0.848 — 00 0.677

A = 0.772 0.848 A = 0.678 00 Aoo = 00 ? J 11 0.745 l*i = O .743 ki = 0*948 6000 6000 60OO

= 0.0001575 min.-1 = 0.0001570 min.”1 = 0.0001580 min.”1 k = 0 .01515x10“- k2 = 0 .01510x10”^ k2 = 0 .01520xl0“ 2 l./m.min* l./m.min. l./m.min. T A B L E 3 9

Compound. Cyclopentanone Dimethyl Ketal

Temp# -0,08° Date 1-11-58 Acid conc# 1 0036x10 3 (moles/lo)

Run 47 Run 48 Run 49

Ketal conc. 0.549 Ketal conc. 0.514 Ketal conc. 0*515 (gms«/l00 mis.) (gms./lOO mis.) (gms./lOO mis.) Calc. Aq = 0.010 Calc# Aq = 0.009 Calc. AQ = 0.009

Time A+ In Time In Time At In * 9 0 - ^ 0 (min.) ^oo—^t (min.) A00_A-t (min.) &oo-&-t

5.i5 0.150 0.203 5 0.140 0.203 5 0.134 0.193 10 0*240 0.361 10 0.230 0,372 10 0,229 0.388 15 0.324 0.530 15 0.308 0.542 15 0.309 0.545 20 0.683 20 o tr 0.397 0.371 0.706 20 0.377 0.Y 23 0.455 0.875 25 0.426 0.875 25 0.431 0.892 30 0.503 1.04 30 0.473 1.05 30 0.475 1.05 35 0.550 1.23 35 0.512 1.215 35 0.515 1.23 40 0.585 1.40 40 0.545 1.38 40 0.553 1.43 45 0.613 1.56 45 0.574 1.56 45 0.583 1,625 oo 0.773 - 00 0.724 — 00 0.723 — o o 0*773 — 00 0.72^ - 00 0.724 -

*if 0.773 = 0.724 >• o o Ao o = ^00 =» 0.724 = 1.40 = 1.42 h -= 1.395 kl = 40 40 40

= 0.0350 min.”^ = 0.03495 min.~^ = 0.0355 rnin.”^ = 33.8 1,,/m.min. /m.min. k 2 = k2 == 33.7 1., k2 == 34.3 1,»/m.min. 1 4 3

T A B L E 4 0

Compound Cyclopentanone Dimethyl Ketal

Temp* 8.42° Date 1-12-58 Acid conc. 4.63x10“^ (molss/l.)

Run 50 Run 51 Run 52

Ketal conc* 0*588 Ketal conc. 0.516 Ketal conc. 0*382 (gms./lOO mis.) (gms./lOO mis*) (gms./lOO mis.) Calc. Ac = 0.010 Calc. AQ = 0.009 Calc. A Q = 0.007

Time A* In Aoo-A> Time A*. In A oo-*o. Time A+ In ^Q-Aq (min.) -^oo-At (min*) A-oo-M, (min.) &oo-M,

3 0.114 0.140 3 0.106 0.147 3 0.079 0.142 6.5 0.218 0*297 6 0.188 0.289 6 0.133 0.263 9 0.288 0.422 9 0.256 0.425 9 0.187 0.406 12 0.352 0.548 12 0.320 0.573 12 0.228 0*525 16 0.426 0.721 16 0.383 0.742 16 0.275 0.683 20 0.490 0.900 20 0.442 0.935 20 0.318 0.855 25 0.560 1.14 25 0.490 1.12 25 0.368 1*095 30 0.603 1.32 30 0.535 1.335 30 0.393 1.245 35 0.642 1.52 35 0.573 1.56 35 0.421 1.44 00 0.819 — 00 0.724 - 00 0.549 00 0.819 — 00 0.722 — 00 0.549 -

■&00 = 0.819 &oo "= 0.723 Aoo == 0.549 . 1.36 - I.295 ki - 1*34 h = 30 30 h - 30

= 0.0447 rain."^ = 0.0453 min. * 0.0431 min.”^ 96,6 lyto.min. = 97.8 1 ./m.min. k2 = k2 = k2 =* 93 0 2 1 ./m.min 1 4 4

T A B L E 4 1

Compound Cyclopentanone Dimethyl Ketal

Temp* 15.86° Date 1-13-58 Acid conc. 2.435xlO“A (moles/l.)

Run 53 Run 54 Run 55

Ketal conc* 0*573 Ketal conc. 0.545 Ketal conc. O .565 (gms./lOO mis.) (gms./lOO mis.) (gms./lOO mis.) Calc. A0 = 0.010 Calc. A0 = 0.010 Calc. Ac = 0.010

Time ju In Time A+ In ^ o - ^ o Time At In Aqq-Aq (min.) ^00- % (min.) ^oo-^t (min.) -^oo-^t

3 0.127 0.161 3 0.124 0.165 3 0.122 0.157 6 0,231 0.339 5.5 0.210 0 . 3 U 6 0.218 0.311 9.5 0.327 0.512 9 0.300 0.489 9 0.306 0.476 12 0.387 0.642 12 0.371 0.658 12 0.376 0.635 15 0.445 0.802 15 0.429 0.817 15 0.435 0.788 18 0.493 0.943 18 0.472 0.958 18 0.482 0.928 21 0.539 1.11 21 0.510 1.10 21 0.526 1.08 24 0.580 1,28 24 0.551 1.28 24 0.563 1.23 27 0.611 1.43 27 0.580 1.43 27 0*599 1.405 00 0.800 - 00 0.763 — 00 0,790 — 00 O .799 - 00 0.762 - 00 0.791 «-«

— 11

i it 0.800 0 0.763 » 0.791 >-

00 0 0 1.28 1.28 :1 = kl “ kl == 1*25 24 24 24

= 0.0533 min.""'*’ = 0*0533 min.”'*' . 0.05201 min. “■*■

219 1./rn.rnin. 219 1./m.min. 2 = k2 " k2 "= 214 1./m.rain. 1 4 5

T A B L E 4 2

Compound Cyclopentanone Diethyl Ketal

Temp* 7.83° Date 2-28-58 Acid conc. 2.455x10""**' (moles/l.)

Run 59 Run 60 Run 61 Ketal conc. 0.473 Ketal conc. 0.431 Ketal conc. 0.488 (gms./lOO mis.) (gms./lOO mis.) (gms./lOO mis.) Calc. A0 = 0.011 Calc. A q = 0.010 Calc. Ac = 0.012

A A In OO— O -|n A o o -A d In A 00-A Time h Time h Time At [min.) Aq q ^A^ (min.) AQQ_At (min#) Ado-A

3 0.091 0.161 3 0.081 0.161 2 0.095 0.167 6 0.163 0.333 6 0.145 0.333 6 0.167 0.333 9 0.221 0.495 9 0.201 0.513 9 0.227 0,496 12 0.270 0.658 12 0.242 0.668 12 0.276 0.652 15 0.315 0.832 15 0.283 0.850 15 0.321 0.822 18 0.345 0.969 18 0.313 1.01 18 0.356 0.978 21 0.377 1.14 21 0.342 1.19 21 0.386 1.135 24 0.407 1.33 24 0.363 1.35 24 0.411 1.285 27 0.427 1.485 27 0.334 1.535 27 0.438 1.48 oo 0.549 — OO 0.488 — 00 0.565 •• oo 0.548 — OO 0.487 - 00 0.562 -

0.549 0.488 A >0 = A do = A do = 0.564 II n 1.36 A l = 1.31 24 24 24

= 0.0554 min.-"*' = O.O567 min.”"*" = 0*0545 min..”'*' k2 = 225.5 l./m,min. k2 = 231 l./m.min. k2 = 222.5 l./m.min, 1 4 6

T A E L ' S 4 3

Compound Cyclopentanone Diethyl Ketal

Temp* -0*05° Date 3-2-58 Acid conc . 4.68x10”^ (moles/l.)

Run 62 Run 63 Run 64

Ketal conc. 0.500 Ketal conc. 0.512 Ketal conc. 0.513 (gms./lOO mis.) (gms./lOO mis.) (gms./lOO mis.) Calc. Aq = 0.012 Calc. Aq = 0.012 Calc. Aq = 0*012

Tijue Aj. In k9°~£°. Time A+ in ^po~ô_ Timp A fn ÔO-Ô (min.) Aoo-^t (min.) A00- t. (min.) ^

4 0.100 0.168 4 0.098 0.161 4 0.099 0,161 8 0.169 0.322 8 0.172 0*325 8 0.174 0.326 12 0*231 0.485 12 0.236 0.491 12 0.238 0.495 16 0.283 O.64S 16 0.290 0.660 16 0.293 0.663 20 0.328 0.811 20 0.335 0.820 20 0.336 0,820 24 0.366 0.975 25 0.382 1.025 24 0.378 1.00 28 0.400 1.145 28 0.411 1.18 23 0,412 1.175 32 0.430 1.33 32 0.432 1.305 32 0.434 1.305 36 0*444 1.43 36 0.453 1.45 36 0.459 1.485 00 0.580 — 00 0.589 — 00 0.539 00 0.580 - 00 0.589 - 00 O .589 - 0.580 ■“o o = ^00 ', 0.589 ^00 == 0.589 II P? 1.30

H * 1.2L kl = klJ. ‘= l . ? l 32 32 32

. - l = 0.0406 = 0.0410 man. * 0.0410 ®in«“^ 86.8 1,./m.min. *2 = k2 == 87.5 1.,/m.min. k2 == 87.5 1. /m.min 1 4 7

T A B L E 4 4

Compound Cyclopentanone Diethyl Ketal

Temp._10e69° Date 3-4-58 Acid conc . 1.315xlO”3 (moles/l.)

Run 65 Run 66 Run 67

Ketal conc. 0,545 Ketal conco 0.507 Ketal conc. 0,649 (gms./lOO rols«) (grus,/l00 mis.) (gms./lOO mis.) Calc. A = 0.012 Calc . A = 0.013 Calc. A = 0,016 0 0 0

Time ^ In ^ o - ^ o Time A In A00-A> T1m« A l In AOp-4o (min.) Aoo—^t (min.) Aoo—At- (min.) Aoo— ^t

5 0.093 0.148 5 0.096 0.144 5 0.112 0.141 10 0.160 0.289 10 0.169 0.289 10 0.200 0.289 15 0.220 0,435 15 0.246 0.470 15 0.272 0.431 20 0.270 0.574 20 0.285 0.577 21 0.353 0.617 25 0.312 0.708 25 0.334 0.728 25 0.392 0.723 30 0.350 0.850 30 0.371 0.859 30 0.439 0.863 35 0.384 1.00 35 o . u o 1.02 35 0.481 1.01 40 0.413 1.135 40 0.440 1.16 40 0.512 1.13 45 0.437 1.27 45 0.462 1.28 45 0.546 1.29 00 0,603 _ 00 0.635 — 00 0.74 8 _ 00 0.603 -CO 0.634 - oc 0.747 - = 0.603 Aoo " Aoo “ 0.635 Aoo == 0.748

kl *= 1.135 *1 - 1.155 ■ i a A 5 40 40 ^ = 40 —T = 0.02835 min.~l = 0.0289 min.“^ . 0.0286 min, “■

= 21.55 1 1»/m.min. 22.0 1 .,/m.min. > 21.75 1 ./m.min k2 " k2 = k 2 - 1 4 8

T A B L E 4 5

Compound Cyclopentanone Diisopropyl Ketal

Temp, -0.02° Date 3-31-58 Acid conc. Io235xl0-A (moles/l.)

Run 71 Run 72 Run 73 Ketal conc. 0.361 Ketal conco 0.263 Ketal conc. 0.431 (gms./lOO mis.) (gms./lOO m l s o ) (gms./lOO mlso) Calc. A = 0.015 Calc. = 0.013. o o Calc. Aq = 0.018

Time JL In .ft>° Time At In Time Aj. In .^QQ-^Q (min.) ^oo-kfc (min.) A00_At (min,) Aoo—At

1 0.080 0.201 1 0.059 0.203 1 0,094 0.199 2 0.153 0.488 2 0.098 0.405 2 0.154 0.385 3 0.171 0.577 3 0.135 0.648 3 0.200 0.562 4 0.205 0.755 4 0.150 0.761 4 0.235 0.718 K 5 - — S 0.171 0,951 5 0.271 0.912 6 0.253 1.095 6 0.195 1.22 6 0.304 1.13 7 0.268 1.23 7 0.204 1.345 7 0,325 1.295 8 0,292 1.485 8 0.221 1.635 8 0,348 1.515 9 0.304 1.65 9 0.226 1.735 9 0.363 1,69 oo 0.375 - 00 0.271 — CO 0,441 oo O.37I — 00 0.273 - 00 0.440 -

oo = 0.373 Aoo = 0.272 ■Aoo - 0.441 1.48? 1.545 1.510 kl - \ - *1 = 8 8 8

= 0.1855 min.-'*" = 0.1930 min.”'*' = 0.1880 min.-'*"

1502 1.,/m.min. 1562 1

t a b l e 46

Compound Cyclopentanone Diisopropyl Ketal

Temp# -0.02° Date 3-31-58 Acid conc. 1.23 5x10"'^ (moles/l.)

Run 74

Ketal conc. 0*378 (gms./lOO mis*) Calc. A = 0.016 o

Time in ^ 0-' t (min«) Aoo—■

1 0.083 0.203 2 0.136 0.395 3 0.185 0.615 4 0.213 0.765 5 0.241 0.942 6 0.266 1.135 7 0.287 1.335 8 0.306 1*55 9 0.316 1.69 oo 0.384 — 00 0.383 - ■< II o o 0.384

1.530 *1 - 8

= 0.1913 min.”^

1550 l./flumia* 1 5 0

T A B L E 4 7

Compound Cyclopentanone Diisopropyl Ketal

Temp. -10,69° Date 4-2-58 Acid conc, 1.251x10“^ (moles/l,)

Run 75 Run 76 Run 77 Ketal conc, 0.366 Ketal conc. 0*420 Ketal conc. 0*398 (gms./lOO mis.) (gms./lOO mis.) (gms./lOO mis.) Calc. Aq = 0.015 Calc. Ac = 0.017 Calc. Aq = 0.016

Time Ai. In i°,1r.A.9, Time a In AQo-Ao Time A, In ^>.0=^P- (min.) ^oo-^t (min.) Aoo-^t (min.) -^oo-^t

5 0.10? 0.293 5 0.122 0.292 5 0.113 0.281 10 0.388 0.652 10 0.202 0.593 10 0.186 0,560 15 0.219 0.830 15 0.251 0.828 15 0.235 0.806 20 0.260 1.13 20 0.303 1.17 20 0.284 1.13 25 0.284- 1.36 25 0.330 1.40 25 0.311 1.365 30 0.311 1.70 30 0.355 1.68 30 0.332 1.60 35 0.325 1.94 35 0.372 1.94 35 0.351 1.87 40 0.338 2.23 40 0.386 2.20 40 0.364 2.11 45 0.351 2.63 45 O .405 2.72 45 0.376 2.40 00 0.376 — 00 0.432 — 00 0.413 — 00 0.277 - 00 0.431 - 00 0.411

2.26 II kl - 2.22 2.15 40 40 40

- 0,0565 min.~^ = 0,0557 min.*"1 = 0.0538 min.“^

kg = 451 l./m.min. kg = 445 1,/m.min. kg = 430 l./m.min. 1 5 1

T A B L E 4 8

Compound Cyclopentanone Diisopropyl Ketal

Temp. -21.13° Date 4-4-58 Acid conc. 2.39x10“^ (moles/l.)

Run 78 Run 79 Run 80

Ketal conc. 0.466 Ketal conc. 0.366 Ketal conc. 0.384 (gms./lOO mis.) (gms./lOO mis.) (gms./lOO mis.) Calc. Ac = 0.019 Calc. AQ = 0.015 Calc. AQ = 0.016

Time in In ^9— Time A* In Time A+ In (min.) ^ Aoo-At (mlnt) ^ & o o - H (min.) ^ Aoo^t

5.2 0.097 0.178 5 0.081 0.195 5 0.078 0.174 10 0.142 0.300 10 0.119 0.329 15 0.129 0.340 15 0.191 0.448 15 0.154 0.470 15 0.163 0.470 20 0.230 0.585 20 0.185 0.610 20 0.195 0.610 25 0.266 0.730 25 0.209 0.737 25 0.221 0.743 30 0.294 0.858 30 0.240 0.930 30 0.250 0.907 35 0.322 1.01 35 0.256 1.045 35 0.276 1.09 40 0.341 1.125 40 0.275 1.20 40 0.291 1.21 45 0.380 1.415 45 0.292 1.365 45 0.304 1.33 oo 0.494 — 0 0 0.386 — 00 0.408 — oo 0 .4?8 - 00 0.387 — 00 0.408 -

II i 0.496 = 0.387 = 0,408 o o Aoo “ Aoo = I.I65 = 1.20 1 . 21 kl = “i ■ *1 - 40 40 40

. -1 . -1 = 0.0291 min. = 0.0300 son. = 0.03025 min.-"* ,/m.mir k2 = 122.0 1 ./m.min. kQ =: 125.5 l./m.min. k 2 “= 126.5 1< 1 5 2

T A B L E 4 9

Compound 3,3-Bimethylcyclopentanone Dimethyl Ketal

Temp* 15.86° Date 4-10-58 Acid conc. 4.88x10-A (moles/l.)

Run 84 Run 85 Run 86

Ketal conc. 0.480 Ketal conc. 0.480 Ketal conc. 0.504 (gms./lOO mis.) (gms./lOO mis.) (gms./lOO mis.) Calc. A0 = 0.015 Calc. A0 = 0.015 Calc. A q = 0.015

Time At In '^99~A? Time At In AR ° r A G Time At In A.P°--° (min.) ^ o o - M . (min.) Aoo-^t (min.) J Aoc_A-t

5 0.104 0*163 5 0.101 0.155 — — — 10 0.181 0.326 10 0.187 0,340 —— — 15 0.247 0.491 15 0.244 0.482 —- - 20 0.302 0.655 20 0.300 0.648 20 0.304 0.637 25 0.347 0.810 25 0.346 0.806 25 0.355 0.807 30 0.391 0.990 30 0.384 0.963 30 0.391 0.947 35 0.428 1.17 35 0.420 1.135 35 0.430 1.125 40 0.452 1.315 40 0.447 1.285 40 0.460 1.285 45 0.481 1.51 45 0.471 1.44 45 O .488 1.465 oo 0.612 — oo 0.611 00 0.628 — oo 0.614 - oo 0.612 - 00 0.631 - II > = 0.613 . 0.612 o o Aoo = Aoo - ° - 630 . 1.285 klA == kl == 1.285 kl ■ 40 40 40 . -i . -1 = 0.0332 = 0.0321 mxn, “ = 0.0321 man. to o i—i 0 = 65.8 1 ,,/m.min. * 65.8 1,,/m.min k2 = »/m min. k2 a k2 ■ 1 5 3

T A B L E 5 0

Compound. 3, 3-Dimethyl cyclopentanone Dimethyl Ketal

Temp. -0.01° Date 4-14-58 Acid conc. 5.19x10“^ (moles/l.)

Run 87 Run 88 Run 89

Ketal conc, O.696 Ketal conc. 0.605 Ketal conc. 0.655 (gms./lOO mis.) (gmse/100 mis.) (gms./lOO mis.) Gale. Aq — 0.021 Calc. Aq = 0.018 Calc. A0 = 0.020

Time A*. In Time A. In Aq o -Aq Time A. In 'W-Ap (min.) ^oo-^t (min.) A00_Afc (min.) ^ o o - H

5.5 0.218 0.262 ✓ 0.187 0.251 5 0.196 0.247 10.5 0.378 0.536 10.5 0.324 0.519 10 0.340 0.506 15.5 0.485 0.775 15 0,412 0.733 15 0.448 0.760 20 0.565 1.01 20 0.489 0.970 20 0.549 1.075 25 0.638 1.26 25 0.557 1.24 — 30 0.690 1.50 30 0.617 1.56 30 0.646 1.51 35 0.737 1.78 37 0.660 1.87 35 0.691 1.80 40 0.770 2.04 40 0.673 1.99 40 0.726 2.10 45 0.789 2.23 45 0.691 2.18 45 0.745 2.33 oo 0.882 — 00 0.777 - 00 0.823 - oo 0.882 - 00 0.777 - 00 0.823 -

11 a _ 0 'oo “ 0.882 0 0.777 noo ~ 0.823 2.04 2.00 2.08 1>*• ~ k.u. = \ = 40 40 40

= 0.0510 min.-1 = 0.0500 min.-1 = 0.0520 min.-1

9.83 l./m.min. 9.64 l./m.rain. 10.02 l./m,mii 2 k2 * k2 * 1 5 4

T A E L E 5 1

Compound 3j3-Eimethylcyclopentanone Dimethyl Ketal

Temp0 7.83° Date 4-18-58 Acid conc. 9»31xLO-^ (moles/l.)

Run 90 Run 91 Run 92

Ketal conc, 0.401 Ketal conc. 0,450 Ketal conc. 0.407 (gms./lOO mlso) (gms./lOO mis.) (gms./lOO mis.) Calc. A0 - 0,012 Calc. A Q = 0.014 Calc. A Q = 0.012

Time A. In Time A. In Time A. In ^22=^2. (min.) oo—t (min.) ^oo-^t (min.) -^oo-^t

5 0.071 0.127 5 0.076 0.118 5 0.073 0,131 10 0.119 0.239 10 0,134 0.239 10 0.121 0.243 15 0.166 0.365 15 0.189 0.372 15 0.167 0*361 21 0.212 0.504 20 0.234 0.495 20 0.207 0.483 25 0.243 0.610 25 0.275 0.620 25 0.246 0.615 30 0.275 0.733 30 0.310 0.746 30 0.278 0.738 36 0.307 0,871 35 0.341 0.866 36 0.309 0.871 40 0,326 0,966 40 0.362 0.958 40 0.329 0.972 45 0.349 1.095 45 0.389 1.09 45 0.349 1.08 oo 0.519 - oo 0.578 — oo 0.521 — oo 0.519 — oo 0.578 - oo 0,523 * 1 II II ? 0.519 0.578 o 0.522 o Aoo = t

0.975 0.980 0.975 klX = kJL l = k l = 40 40 X 40

ss 0.0244 min,”^ = 0.0245 min.~^ = 0.0244 min.”"**

26.2 l./m.min. 26.3 l./m.min. 26.2 l./m.min. k2 = k2 " k2 = 1 5 5

T A B L E 5 2

Compound 2-Methylcyclopentanone Dimethyl Ketal

['emp. 15*86° Date 6-9-58 Acid conc. 1.218xl0“A (moles/l.)

Run 96 Run 97 Run 98

Ketal conc. 0.449 Ketal conc. 0.441 Ketal conc. 0.337 (gms./lOO mis.) (gms./lOO mis.) (gms./lOO mis.) Cal<3. Ao =: 0.030 Calc. A q =: 0.029 C 0,1c « Aq — 0.022

A_ _ A A_ A.. A. Time 00— 0 a In 0 Time Af in °°“ 0 A+X Time (min.) Aq o —At (min.) Aoo—At (min.) Aq o —At

5 0.167 0.231 5 0.162 0.231 5 0.129 0.239 10 0.270 0.445 10 0.265 0.451 10 0.204 0.448 15 0.351 O.658 15 0.336 0.642 15 0.263 0.648 20 0 . 41 a 0.875 20 0.401 0.855 20 0.312 0.854 25 0.460 1.035 25 0.439 1.005 25 0,344 1.015 30 0.501 1,225 -- - 30 0,376 1 .2 0 35 0.539 1.445 — - — 35 0.403 1.40 40 0.561 1 .6 0 —— - 40 0.419 1.535 45 0.578 1.73 — - — 45 0.434 1.685 oo 0.696 — 00 0.676 — 00 0.529 — oo 0.696 - 00 0.678 - 00 0.527 - ii

O.696 0 0.528 Aoo = 0.677 Aoo = 1.565 0.825 1*53 = *1 = 40 *1 40 40

= 0.0391. min.-^ = 0.0412 min.-1 - 0.0382 min,-"*" /m.min. l./m.min k? - 321 1,/m.min. ko = 339 1. k 0 - ■. 314 1 5 6

TABLE 5 3

Compound 2-Methylcyclopentanone Dimethyl Ketal

Temp« 7 * 8 3 ° Date 6-11-58 Acid conc,, 2 .32x10“^ (moles/l.)

Run 99 Run 100

Ketal conc, 0.278 Ketal conc,. 0.334 (gms./lOO mis.) (gnu3./100 mis.) Calc, a 0 =: 0.018 Calc. A0 == 0.022

A A Time In OO— O Time In Aoo-Ao Kt A+t (min,) Aqo— (min.) Aqo—At

5 0,090 0.191 5 0.109 0.191 10 0,140 0.344 10 0.169 0.351 16,5 0.196 0.554 15 0.224 0.519 20 0,221 0.668 20 0.268 0.678 26 0.259 0.858 25 0.306 0.842 30 0.278 0.975 30 0.326 0.940 35 0.300 1.125 35 0.368 1.185 40 0.314 1.23 40 0.379 1.255 46 0.336 1.43 45 0.393 1,36 oo 0.435 - oo 0.521 — oo 0.437 — oo 0.521 - II o o 0.436^oo A = 0.521 & II 1.245 % = 1.27 40 40

= 0*0311 min. 1 = 0.03175 min."1 134 l./m.min. k2 = k2 = 137 l./m.min. 1 5 7

T A B L E 5 4

Compound 2-Jle t hylc y clopentanone Dimethyl Ketal

Temp. 0.00° Date 6-13-58 Acid conc. 5.19xL0~4 (moles/l,)

Run 101 Run 102

Ketal conc. 0.221 Ketal conc. 0,323 (gms./lOO nils.) (gms./lOO mis,) Calc, Ac = 0,015 Calc, A q = 0,022

Time In ^ . ? ~ A ° Time A^ In ^oo-^-o (min,) (min.) Aoo-At

6 0.081 0.215 6 0.110 0.203 12 0.124 0.389 12 0.178 0.392 18 0.159 0.554 18 0.229 0.565 24 0.190 0.727 24 0.275 0.746 30 0.216 0.900 30 0.306 0.900 36 0.235 1.05 36 0.335 1.06 42 0.253 1.21 42 0.357 1.195 48 0.264 1.33 49 0.384 1.40 54 0.271 1.41 54 0.395 1.50 oo 0.354 - oo 0.501 — oo o.?54 — oo O .502 -

Aoo = 0.354 Aoo == 0.502

kl == 1*24 h =• 1.22 48 48

= 0.0279 min.“^ = 0.027? min,~^

k2 = 53*8 l./m.min. k 2 = 5 3 .U l . / m . m i n . 158

T A B L E 5 5

Compound. Cyclohexanone Dimethyl Ketal

Temp* 28*15° Date 1-7-53 Acid conc. 2.4Qxl0“A (moles/l.)

Hun 107 Run 108 Run 109

Ketal conc. 0*818 Ketal conc* 0.780 Ketal conc. 0.818 (gms./lOO mis.) (gms./lOO mis.) (gms./lOO mis.) Calc. AQ = 0.008 Calc. A0 = 0.008 Calc. A0 = 0.008

Time A+ In Time A+ In j s s A Time A+ In (min.) Aoo-At (min.) ^oo-^t (min.) ^oo-^t

5 0.143 0.157 5 0.137 0.161 5 0*144 0.159 10 0.262 0.318 10 0.234 0.300 10 0,264 0.318 15 0.355 0.467 15 0.321 0.444 15 O.36O 0.470 20 0.439 0.623 20 0.401 0.595 20 0.443 0.626 25 0.509 0.773 25 0.463 0.716 25 0.519 0.786 30 0.573 0.939 30 0.523 0.888 30 0.584 0.952 35 0.628 1.095 35 0.572 1.03 35 0.633 1.10 41*6 0.680 1.28 40 0.618 1.195 40 0.681 1.265 45 0,716 1.43 45 0.652 1.335 45 0,722 1.43 oo 0.939 — oo 0.883 — 00 0.945 — oo 0.?,3? - oo 0.882 - 00 0 o % 5 -

Aoo “ 0.939 Aoo 0.883 Aoo = 0.945 kl = 1.27 kl = 1.1? kl = 1,265 40 40 40

= 0.03175 min.”1 = 0.02975 min.-1 = 0.03165 min.-**

132.2 l./m.min* k2 = k2 = 124.4 l./m.min. k2 = 131«9 l./m.mir 1 5 9

T A B L E 5 6

Compound Gyclohexanone Dimethyl Ketal

Temp* 15.31° Date 1-3-58 Acid conc. 1.021xl0“3 (moles/l.)

Run 110 Sun 111 Run 112 Ketal conc. 0,671 Ketal conc, 0,640 Ketal conc. 0.653 (gms./lOO mis.) (gms./lOO mis.) (gms./lOO mis.) Calc, A = 0,007 Calc. A = 0.006 Calc. A = 0.006 O 0 0

Time A, In A°°-A° Time Ax In ^00-^0 Time A+ In ^o-A) (min.) ' & 0O-H, (min.) Aoo-At (min.) Aoo-A-t

5 0.101 0.133 5 0.095 0.131 5 0.099 0.136 10 0.183 0.263 10 0.175 0,262 10 0.180 0.266 15 0.252 0.389 15 0.242 0.392 15 0.248 0.392 20 0.315 0.519 20 0.302 0.525 20 0.305 0.512 25 0.371 0.650 25 0.352 0.645 25 0.359 0.642 30 0.419 0.779 30 0.397 0.770 30 0.407 0.775 36.5 0.469 0.931 35 0.440 0.904 35 0.449 0.905 40 0.496 1.025 40 0.474 1.025 40 0.483 1.025 45 0.530 1.16 45 0.506 1.16 45 0.517 1.16 0 0 0.767 - 0 0 0.738 ~ 0 0 0.750 - 0 0 0.770 — 0 0 0.738 0 0 0.751 — <*: 11

as 0.738 0 0 OO 0.769 ^ 0 0 0.751

1.03 kj_ - 1.0,3 kl = 1.025 40 40 40 . -1 = 0.02575 min. = 0.02575 min.~'k = 0.02565 min.-^ X 11 CM II 25.2 1. /m.min. 25.2 1./m.min. 25.1 1. /m.min.

M k2 " 1 6 0

T A B L E 5 7

Compound Cyclohexanone Dimethyl Ketal

Team. -0.07° Date 1-9-58 Acid conc. 5.19x110“^ (moles/l*)

Run 113 Run 114 Run 115

Ketal conc. 0.803 Ketal conc. 0,314 Ket al c one. 0 . 8 53 (gms./lOO mis.) (gms./lOO mis.) (gms./lOO mis.) Calc. A0 - 0.008 Calc. A0 = 0.008 Calc. A-0 = 0.009

A A Time A, In d o o A o Time A. In 00— 0 Time In Aoo-A t t Ai.t (min.) ■^oo-^t (min.) Aoo-^t (min.) •^00—A

10 0.162 0.182 10 0.161 0.3.80 10 0.204 0.219 20 0.285 0.358 20 0.285 0.354 20 0.317 0.372 30 0.381 0.519 30 0.384 0.519 30 0.424 0.539 40 0.460 0.672 40 0.468 0.683 40 0.506 0.693 50 0.536 0.846 50 0.540 0.846 50 0.584 0.862 60 0,596 1.01 60 0.599 1.01 60 0.644 1.015 70 0 .6^2 1.16 70 0.649 1.165 70 0,700 1.135 80 0.685 1.32 80 0.698 1.35 80 0.742 1.33 90 0,725 1.495 90 0,727 1.48 90 0.785 1.51 oo 0.931 - CO 0.938 - 00 1.005 — oo — oo 0.940 - 00 1.004 -

0.932 ^oo = A o = 0.939 *00 = 1.005 ki = 1.33 1.29 kl = !•??? A = 80 80 80

= 0.0167 min.-1 = O.OI665 roin.~~ - 0.01610 rrdn.~1

3.22 1 ./m.min. 3.21 1 k p = k2 - k 2 = ./m.min. 3.31 1 ./m.min. 161

Cyclohexanone Diethyl Ketal

Temp. 7.83° Date 2-28-58 Acid conc. 1.029x10“^ (moles/l)

Run 119 Run 120 Run 121

Ketal conc. 0.450 Ketal conc. 0.413 Ketal conc. 0.387 (gms./lOO mis.) (gms./lOO mis.) (gms./lOO mis.) Calc. Ac = 0.009 Calc. A 0 - 0.008 Calc. A 0 0.008

Time At i„ A 00-A0 Time A+ ln A °0“Ao Time At In Aoo“A 0 (min.) ^ o o ' H (min.) ^ A^-Afc (min.) Aoo-At

5 0.074 0.161 5 0.083 0.207 5 0.066 0.165 10 0.125 0.307 10 0.116 0.315 10 0.111 0.318 15 0.171 0.461 15 0.160 0.479 15 0.153 0.482 20 0.214 0.629 20 0.195 0.631 20 0.186 0.636 25 0.247 0.780 25 0.226 0.788 25 0.216 0.798 30 0.274 0.924 30 0.251 0.935 31 0.245 0.980 36 0.305 1.12 35 0.279 1.13 35 0.263 1.12 40 0.321 1.24 40 0.299 1.30 40 0.282 1.285 45 0.337 1.37 45 0.315 1.46 45 0.298 1.45 oo 0.448 — oo 0.409 — oo 0.388 — oo 0.448 — 00 0.406 —- 00 0.386 —

A 0 = 0.448 0.408 A 0= Ao - 0.387 k x - 1.24 1.275 k ls k l “ 1.285 40 40 40

. -1 . -1 = 0.0310 m i n . ^ = 0.0319 min. = 0.0321 min. M ii CM 31.2 l./m.min. 30.1 l./m.min. k 2= 31.0 l./m.-min. k2 = 162

TABLE 59

Compound Cyclohexanone Diethyl Ketal

Temp. -0.05° Date 3-2-58 Acid conc. 2.595x10“® (moles/l)

Run 122 Run 123 Run 124

Ketal conc • 0.625 Ketal conc . 0.703 Ketal conc. 0.493 ( gms. /100 mis.) (gms./lOO mis •) (gms./lOO mis. ) Calc 0.012 Calc * A o = • A 0 = <0.014 Calc • Ao = 0.010

■. a 00-a0 Art -Art Time A^. Time At. Time Ah In A 00_A0

I In oo o

(min (mi n.) (min. t>l o cf • ) o il O o o -*b ) ! ! o !

5 0.076 0.113 5 0.085 0.114 5 0.061 0.122 10 0.136 0.231 10 0.152 0.231 10 0.121 0.270 15 0.191 0.340 15 0.211 0.347 15 0.151 0.354 20 0.237 0.470 20 0.269 0.479 20 0.192 0.489 25 0.281 0.594 25 0.316 0.600 25 0.225 0.610 30 0.317 0.709 30 0.356 0.712 30 0.264 0.775 35 0.351 0.833 35 0.391 0.828 35 0.280 0.852 40 0.379 0.945 40 0,425 0.952 40 0.302 0.966 45 0.410 1.085 45 0.454 1.07 45 0.322 1.085 00 0.613 — 00 0.683 00 0.481 — CO 0.613 — CD 0.684 — 00 0.481

A 0o= 0.613 =0.684 tl 0.481 o Aoo o

k l = 0.955 k l :=0.955 kl s 0.970 40 40 40

= 0.0239 min . " 1 =0.0239 min . -1 25 0.0243 min . ”1 kg = 9*20 l./m.Bin. kg =9,20 l./m.min kg = 9.36 1,/m,-min 163

TABLE 60

Compound Cyclohexanone Diethyl Ketal

Temp. 15.86° Date 3-3-58 Acid conc. 4.61xl0*4 (moles/l)

Run 125 Run 126 Run 127

Ketal conc. 0.541 Ketal conc. 0.500 Ketal conc. 0.480 (gms./lOO mis.) (gms./lOO mis.) (gms./lOO mis.) Calc. A Q - 0.011 Calc.. A 0 = 0.010 Calc. A q = 0.009

Time A^ -]n *.oo~&o Time Aj. A 0C)-Aq Time A* A 00-A0 (min.) AQq —A j. (min.) a oo-A t (min.) Aq o -A,.

5 0.109 0.207 5 0.103 0.215 5 0.099 0.215 10 0.189 0.419 10 0.176 0.425 10 0.172 0.435 15 0.256 0.640 15 0.239 0.648 16 0.240 0.690 20 0.307 0.846 20 0.287 0.863 20 0.309 1.045 25 0.348 1.045 25 0.325 1.07 25 0.314 1.075 30 0.386 1.28 30 0.356 1.275 30 0.349 1.33 35 0.415 1.51 35 0.383 1.50 35 0.374 1.55 40 0.433 1.675 40 0.401 1.685 40 0.393 1.77 45 0.451 1.88 45 0.421 1.94 45 0.409 2.00 CO 0.530 __ CO 0.490 __ 00 0.4-73 — 00 0.529 CO 0.490 — 00 0.471 « a m

0.530 0.490 II 0.472 Oil A q o = o o o

1.68 1.71 1.78 kl “ k l= kl = 40 40 40

= 0.0420 min. ^ = 0.0427 mi n. ”1 = 0.0445 min.”k

91.0 l./m.min. k2 = 92.7 l./m.min. 96.4 1,/m.min. k2 k2 164 TABLE 61

Compound Cyclohexanone Diisopropyl Ketal

Temp. -0.02° Date 3-31-58 Acid conc. 1 . 2 3 5 x 10“ 4 (moles/l)

Run 131 Run 132 Run 133

Ketal conc. 0.407 Ketal conc. 0,241 Ketal conc. 0.355 (gms./lOO mis.) (gms./lOO mis.) (gms./lOO mis.) Calc. A 0 = 0,012 Calc. A 0 = 0.007 Calc. A 0 = 0.010

Time At ln A oo“Ao Time Af. A oo"A o Time A+ lnAoo”Ao (min.) A oo""^M: (min.) A 00-At (min.) A 00“At

3 0.068 0.178 3 0.047 0.215 3 0.060 0.183 6 0.112 0.344 6 0.074 0.392 6 0.100 0.354 9 0.150 0.512 9 0.094 0.545 9 0.134 0.531 12 0.183 0.688 12 0.112 0.708 13 0.173 0.780 15 0.214 0.883 15 0.129 0.893 15 0.189 0.904 18 0.239 1.08 19 0.419 1.16 18 0.209 1.08 21 0.256 1.235 21 0.158 1.31 21 0.225 1.25 24 0.275 1.46 24 0.166 1.43 24 0.239 1.43 27 0.288 1.62 27 0.173 1.62 27 0.254 1.665 CO 0.355 — 00 0,213 — 0 0 0.310 — oo 0.356 — oo 0.214 — 00 0.312 —

A0o—0.356 A oo=0 .2 U A oo“ 0.311

=1.435 =1.45 k l k l k l = 1.43 24 24 24

=0.0598 mi n. =0.0604 min.-^ = 0.0596 min."’'*' kg ~ 484 l./m.min. kg = 489 l./m.min. kg = 483 l./m.min. 165

TABLE 62

Compound Cyclohexanone Diisopropyl Ketal

Temp. -10.69 Date 4-2-58 Acid conc. 2.37x10“^ (moles/l)

Run 134 Run 135

Ketal oonc. 0,393 Ketal oonc. 0.322 (gms./lOO mis.) (gms./lOO mis.) Calc. A q = 0.011 Calc. A 0 = 0.009

Time Af -|n Aoo“Ao Time ln Aoo~Ao (min.) ^oo'-^t (min.) A oo_At

5 0.059 0.153 5 0.051 0.161 10 0.094 0.281 10 0.076 0.270 15 0.121 0.395 150.106 0.419 20 0.151 0.537 20 0.125 0.525 25 0.176 0.S73 25 0.151 0.693 30 0.196 0.797 30 0.162 0.775 35 0.219 0.959 35 0.179 0.913 40 0.233 1.075 40 0.193 1.045 45 0.256 1.295 45 0.209 1.215 00 0.346 — 00 0.294 — oo 0.349 00 0.291 —

=0.348 Aoo A oc,=0.293

kl =1.075 k l =1.045 40 40

=0.02685 min.“* =0.0261

k2 =113.2 l./m.min. kg =110.2 1.,/m.min. 166

TABLE 63

Compound Cyclohexanone Diisopropyl Ketal

Temp. -21.13° Date 4-4-58 Acid conc. 1.325x10”® (moles/l)

Run 136 Run 137 Run 138

Ketal conc. 0.415 Ketal conc. 0.490 Ketal conc. 0.460 (gms./lOO mis.) (gms./lOO mis.) (gms./lOO mis.) Calc. A 0 = 0.012 Calc. A 0 = 0.014 Calc. A 0 ~ 0.013

Time A^. A 00-A0 Time Aj. ln K o ' K Time A|- ^•oo~^,o (rain.) (mn.) (min.) A 00-At

5 0.063 0.157 5 0.072 0.151 5 0.069 0.157 10 0.103 0.300 10 0.121 0.300 10 0.114 0.304 15 0.139 0.445 15 0.166 0.456 15 0.151 0.442 20 0.172 0.601 20 0.199 0.596 20 0.191 0.615 25 0.203 0.775 25 0.232 0.746 25 0.218 0.753 30 0.222 0.900 30 0.259 0.896 30 0.246 0.920 35 0.242 1.05 35 0.278 1.015 35 0.267 1.07 40 0.259 1.195 40 0.302 1.19 40 0.289 1.25 45 0.274 1.35 45 0.316 1.305 45 0.301 1.36 CO 0.364 -- oo 0.428 __ oo 0.400 — ■ oo 0.365 00 0.429 00 0.400 —

A q q —0.365 A oo=0.429 A 00—0.400

=1.195 k l k l =1.18 k l = 1.22 -— & 4o 40

=0.02990 min.""*- =0.02950 min. =0.0305 min. ” 3

=22.60 l./m.min. =22.25 l./m.min. =23.00 l^tumix k2 k2 k2 167

TABLE 64

Compound 3,3-Dimethylcyclohexanone Dimethyl Ketal

Temp. 28.14° Date 5-2-58 Acid conc. 1.20x10"^ (moles/l)

Run 142 Run 143

Ketal conc. 0.455 Ketal conc. 0.285 (gms./lOO mis.) (gms./lOO mis.) Calc. A = 0.020 Calc. A 0 = 0.013

Time At-. -jn &oo~&o Time A+. Ao 0-A0 (min.) Aoo-^t (min.)

5 0.086 0.158 5 0.061 0.182 10 0.144- 0.319 10 0.095 0.333 15 0.1910.470 15 0.132 0.531 20 0.233 0.629 21 0.157 0.690 25 0.268 0.784 25 0.178 0.846 30 0.300 0.951 30 0.198 1.02 35 0.327 1.115 35 0.210 1.145 40 0.346 1.25 40 0.225 1.32 45 0.366 1.42 45 0.240 1.54 CO 0.476 — 00 0.301 -- 00 0.477 00 0.303 — II

o 0.477 o Aoo= 0.302

k l = 1*265 k l = 1*33 40 40

= 0.0316 min . _1 « 0.03325 min . " 1

k£ = 263 l./m.min. kg = 277 l./m.min. 168

TABLE 65

Compound 3,3-Dimethylcyclohexanone Dimethyl Ketal

Temp. 0.00° Date 5-2-58 Acid conc. 2.59x10"*^ (moles/l)

Run 144 Run 145

Ketal conc. 0.427 Ketal conc. 0.237 (gms./lOO mis.) ( gms ./lOO mis • ) Calc. A q = 0.019 Calc. A 0 = 0.011

10 0.086 0.167 10 0.055 0.191 24 0.158 0.385 20 0.087 0.354 30 0.181 0.464 30 0.105 0.460 40 0.219 0.612 40 0,127 0,610 50 0.256 0.783 50 0.147 0.765 60 0.279 0.903 60 0.160 0.884 70 0.308 1.085 70 0.175 1.04 80 0.328 1.23 80 0.187 1.18 90 0.343 1.355 90 0.197 1.32 00 0.455 — 00 0.264 — 00 0.456 00 0.265 —

A oo= 0.456 A oo~ 0.265

kl = 1.22 k l “ 1.14 80 80'

= 0.01526i min."-*- = 0.01425 min.'

k2 = 5.88 l./m.min. k 2 = 5.50 1 • /m • mi i 169

TABLE 66

Compound 3,3,5,5-Tetramethyleyclohexanone Dimethyl Ketal

Temp. 15.34° Date 5-16-58 Aoid oonc. 2.31xlO“4 (moles/l)

Run 149 Run 150 Run 151

Ketal conc. 0.361 Ketal conc. 0.284 Ketal conc. 0.312 (gms./lOO mis.) (gms./lOO mis.) (gms./lOO mis.) Calc. A q - 0.041 Calc. A q = 0.032 Calc. A q * 0.035

Time A* A 00-AQ Time A+. ln Aoo"Ao Time A^. -|n ^’oo'~^‘o (ndn.j Aoo-Afc Cnan.) A ^ (min.) A00-At

5 0.076 0.105 5 0.064 0.122 5 0.065 0.105 10 0.107 0.217 10 0.097 0.266 10 0.096 0.227 15 0.148 0.363 15 0.114 0.347 15 0.122 0.344 21 0.174 0.476 20 0.134 0.455 20.5 0.149 0.479 25 0.214 0.680 25 0.157 0.596 25 0.166 0.577 30 0.214 0.680 30 0.174 0.709 30 0.188 0.718 35 0.235 0.804 35 0.190 0.833 35.5 0.205 0.841 40 0.252 0.920 40 0.201 0.928 40 0.219 0.955 45 0.267 1.03 45 0.214 1.055 45 0.235 1.11 oo 0.391 — 00 0.311 — CO 0.334 — 00 0.393 — 00 0.311 -- 00 0.334 —

: 0.392 A oo=0.311 ■^•oo A oo =0.334 k l =0.920 k l = 0.938 k l = 0.953 40 40 40

=0.0230 min."^ =0.02345 min . -1 =0.0238 mi n.

=99.6 l./numin. k2 k2 =101.5 l./m.min. k2 =103.0 l./m.min. 170

TABLE 67

Compound 3,3,5,5-Tetramethylcyclohexanone Dimethyl Ketal

Temp. 0.00° Date 5-18-58 Acid conc. 2.595x10"^ (moles/l)

Run 152 Run 153

Ketal conc. 0.555 Ketal conc. 0.383 (gms./lOO mis.) (gms./lOO mis.) Calc. AQ = 0.038 Calc. A 0 = 0.043

5 0.077 0.127 5 0.082. 0.114 10 0.115 0.266 10 0.127 0.266 15 0.145 0.389 15 0.165 0.409 20 0.173 0.521 20 0.198 0.557 25 0.200 0.669 25 0.225 0.698 30 0.222 0.806 30 0.248 0.833 35 0.240 0.931 35 0.271 0.990 40 0.255 1.055 40 0.289 1.13 45 0.269 1.18 45 0.306 1.29 oo 0.373 — 00 0.404 o o 0.571 -- o o 0.409 — II > 0.372 o o A-oo= 0.406

k l “ 1.055 ki = 1.11 40 40 —I = 0.0264 min. = 0.02775 min . " 1

l./m.min. k2 = 10.17 l./m.min. k2 = 10.70 171

TABLE 68

Compound 3,3,5,5-Tetramethylcyclohexanone Dimethyl Ketal

Temp. 28.12° Date 5-21-58 Acid conc. 1.20x10“^ (moles/l)

Run 154 Run 155

Ketal conc. 0.321 Ketal conc. 0.304 (gms./lOO mis.) (gms./lOO mis.) Calc. A o = 0.036 Calc, A c = 0.034 Time A+ lri A oo~A o Time A^. A oo*"Ao (min.) A 00-At (min.) Aoo-At

3 0.084 0.168 3 0.085 0.191 6 0.133 0.375 6 0.124 0.365 9 0.168 0.556 9 0.163 0.576 12 0.201 0.761 12 0.190 0.756 15 0.228 0.966 15 0.213 0.935 18 0.2481.15 18 0.235 1.15 21 0.266 1.33 21 0.253 1.365 24 0.280 1.545 24 0.267 1.57 27 0.293 1.765 26 0.272 1.66 oo 0.346 — oo 0,327 CO 0.346 — oo 0.328 —

Aoo~ 0.346 A oo= 0.328 1.535 1.52 klX = k 1X = 24 ~ T T

s= 0.0640 min.“^ = 0.0634: min.*’-^

k2 = 534 1.,/m.min. k2 = 528 1./m.min. 172

TABLE 69

Compound 2-Methylcyclohexanone Dimethyl Ketal

Temp. 15. 86° Date 6-9-58 Acid conc. 4.61x10 ”4 (moles/l)

Run 159 Run 160 Run 161

Ketal conc. 0.499 Ketal conc. 0.512 Ketal conc. 0.516 (gms./lOO mis.) (gms./lOO mis.) (gms./lQQ mis.) Calc. A q ~ 0.024 Calc. A 0 = 0.025 Calc. A 0 = 0.025

Time A^ In ■^00”^'0 Time Aj- ■^■oo“A 0 Time Af in ^-oo“-^o (min.) ^oo“^ (min.) ^■oo”,'^t (mi n.) A 00-A-fc

5 0.146 0.231 3 0.098 0.129 3 0.099 0.123 10 0.247 0.470 6 0.168 0.270 6.!5 0.181 0.285 15 0.321 0.712 9 0.231 0.415 9 0.232 0.399 18 0.361 0.836 12 0.285 0.560 12 0.286 0.536 21 0.395 0.977 15 0.327 0.688 15 0.333 0.672 24 0.422 1.11 18 0.3S8 0.833 18 0.368 0.788 27 0.445 1.23 21 0.402 0.974 21 0.404 0.920 30 0.466 1.365 24 0.432 1.115 24 0.432 1.04 33 0.483 1.48 27 0.459 1.26 27 0.464 1.20 oo 0.618 — 00 0.631 00 0.652 oo 0.617 — CO 0.631 oo 0.655 —

A oo=0.618 A oo=0.631 A q q =0 * 654

=1.155 =1.115 =1.085 k l kX l k l 25 24 24

=0.0461 min.”^ =0.0464min. =0.0452min.”^ kg =100.0 l./m.min. kg =100.5 l./m.min. kg =98.0 l/n.min. 173

TABLE 70

Compound 2-Methylcyclohexanone Dimethyl Ketal

Temp. 7.83° Date 6-11-58 Acid conc. 1.029x10"® (moles/l)

Run 162 Run 163 Run 164

Ketal conc. 0.520 Ketal conc. 0.416 Ketal conc. 0.407 (gms./lOO mis.) (gms./lOO mis.) (gms./lOO mis.) Calc. A q = 0.026 Calc. A c = 0.020 Calc. A 0 = 0.020

Time A,. lQ ^oo"A o Time A+_ 1rT A oo“A o Time A+ •)„ Aoo-Ao (nan.) A oo"At (min.) Aoo-Afc (min.)

3 0.093 0.118 3 0.075 0.118 30.072 0.109 6 0.149 0.223 6 0.118 0.219 6 0.119 0.219 9 0.200 0.333 9 0 .158 0.326 9 0.165 0.337 12 0.251 0.454 13 0.207 0.470 12 0.201 0.441 15 0.291 0,562 16 0.240 0.582 15 0.236 0.556 18 0.326 0.670 18 0.257 0.647 18 0.264 0.657 21 0.361 0.789 21 0.290 0.780 21 0.296 0.782 24 0.394 0.912 24 0.309 0.866 24 0.314 0.867 27 0.416 1.01 27 0.332 0.982 27 0.338 0.985 oo 0.640 — 00 0.519 00 0.52S «•«* oo 0.641 OO 0.521 — 00 0.531

Aoo=0.641 A oo=0.520 A q O=0.530 k x =0.900 k I =0,870 k l =0.875 24 24 24

=0.0375 =0.0363 min. =0.0365 min.”^- k£ -36.5 l./m.min. k 2 =35.3 l./m.min. k2 =35*5 l./m.min. 174

TABLE 71

Compound 2-Methylcyclohexanone Dimethyl Ketal

Temp. 0.00° Date 6-13-58 Acid conc. 2.595x10“’® (moles/l)

Run 165 Run 166 Run 167

Ketal conc. 0.542 Ketal conc. 0.597 Ketal conc. 0.550 (gms./lOO mis.) (gms./lOO mis.) (gms./lOO mis.) Calc. Ac = 0.027 Calc. AQ = 0.029 Calc. A c = 0.027

Time A+. ip ^ o ~ A o Time Af-, ir, ^-oo^o Time A-oc~&o (min.) (min.) "\,0-At (min.) ^ o o " ^

5 0.112 0.140 5 0.120 0.135 5 0.112 0.136 10 0.186 0.281 10 0.202 0.274 10 0.188 0.270 15 0.249 0.419 15 0.272 0.411 15 0.258 0.415 20 0.306 0,562 20 0.333 0.548 20 0.313 0.545 25 0.356 0.705 25 0.384 0.678 25 0.362 0.680 30 0.397 0.842 30 0.432 0.820 30 0.406 0.820 35 0.432 0.975 35 0.471 0.952 35 0.440 0.940 40 0.467 1.13 40 0.507 1.09 40 0.471 1.065 45 0.490 1.25 45 0.538 1.225 45 0.499 1.19 00 0.677 — CD 0.749 00 0.704 — oo 0.677 — CO 0.750 — CO 0.705

A oo=0.677 ^oo=0-760 A oo=0. 705

=1.115 kl k l =1.09 k l =1.095 40 40 40

=0.0279 min."^ =0.0272 min.-'*' =0.02 735 min.” ko =10.75 l./m.min. =10.48 l./m.min. (mt k 2 k 2 =10,54 l./m.mi TABLE 72

Compound Cycloheptanone Dimethyl Ket&l

Temp. -0.04° Date 2-2-58 Acid cono. 2.47x10"^ (moles/l)

Run 171 Run 172. Run 173

Ketal conc. 0.737 Ketal conc. 0.720 Ketal conc. 0.719 (gms./lOO mis.) (gms./lOO mis.) (gms./lOO mis.) Calc. A„ = 0.010 o Calc. A 0 * 0.010 Calo. A 0 = 0.010

Time Af. ôo"ô Time A+, in -ôo“^-o Time At ln ôo'ô (min.) A^-Afc (min.) A 00-At. (min.) ,^'Oo'"'^t

3 0.117 0.131 3 0 . 1 1 1 0.122 3 0.121 0.133 6 0.212 0.258 6 0.204 0.251 6 0.216 0.263 9 0.295 0.385 9 0.286 0.382 9 0.300 0.396 12 0.367 0.512 12 0.357 0.507 12 0.367 0.510 15 0.437 0.656 15 0.420 0.631 15 0.434 0.645 18 0.493 0.784 18 0.477 0.765 18 0.485 0.761 21 0.551 0.935 21 0.526 0.892 21 0.536 0.890 24 0.587 1.045 24 0.570 1.025 24 0.581 1.055 26 0.610 1.12 27 0.606 1.145 27 0.618 1.145 00 0.902 CO 0.885 -- CO 0.905 00 0.900 -- CO 0 . 884 00 0.900 —

A oo=0.901 A OC=0.884 A oo=°.903

=1.045 =1.025 =1.030 *1 kJL l k.l 24 24 24

=0.0435 min."1 =0.0427 min."1 =0.0429 min.”' kg =176.2 l./m.min. =173.2 k 2 l./m.min k 2 =173.8 l./m.nd 176

TABLE 73

Compound Cycloheptanone Dimethyl Ketal

Temp. 7.93° Date 1-21-58 Acid Conc. 2.43x10“^ (moles/l)

Run 174 Run 175 Run 176

Ketal conc. 0.669 Ketal conc. 0.598 Ketal conc. G.687 (gms./lOO mis.) (gms./lOO mis.) (gms./lOO mis.)

Calc. A_o = 0.009 Calo. A Q = 0.008 Calc. A0 = 0.009

Time A+ ^ o o "^o Time ^ 1n A 00~Ao Time A^ -|n &oo~&o (min.) A-oo"'-Lt A 00-Afc (min.) -^00 “^

2.5 0.227 0.304 2.5 0.197 0.300 2.5 0.210 0.274 5 0.343 0.513 5 0.333 0.587 5 0.364 0.555 7.5 0.498 0.880 7.5 0.455 0.940 7.5 0.487 0.850 10 0.587 1.18 10 0.520 10 20 10 0.578 1.14 12.5 0.644 1.44 12.5 0.571 1.46 12.5 0.639 1.40 15 0.696 1.73 15 0.615 1.76 15 0.690 1.68 17.5 0.727 1.97 17.5 0.650 2.08 17.5 0.726 1.95 20 0.754 2.23 20 0.667 2.16 20 0.755 2.23 22.5 0.775 2.51 22.5 0.691 2.66 22.5 0.768 2.39 CO 0.841 — 00 0.740 «... 00 0.843 -- 00 0.844 00 0.744 — 00 0.846 —

A00 0.843 •^■00 0.742 Aqo ~ 0.845 ki * 2.28 2.36 2.23 k l = kX l = 20 20 20

7 0.114 min.”"*- = 0.118 min."* - 0.1115 min.” - k£ = 468 = 486 l./m.min. = 459 l^n.min. 177

TABLE 74

Compound Cycloheptanone Dimethyl Ketal

Temp. -10.69° Date 1-25-58 Acid conc. 4.74x10”^ (moles/l)

Run 177 Run 178 Run 179

Ketal conc. 0.632 Ketal conc. 0.691 Ketal conc. 0.690 (gms./lOO mis.) (gms ./l00 mis.) (gms ./lOQ mis.) Calc. Ac = 0.009 Calc. A q = 0.009 Calc. A c ® 0.009

Time A*. 1t, ^ o o ^ o Time At in AooAo Time ^ m AooA° ’min.) Aoo-At (min.) Aoo-At (min.) AocAt

5 0.089 0.109 5 0.094 0.105 5 0.096 0.109 10 0.155 0.207 10 0.168 0.203 10 0.162 0.199 15 0.214 0.304 15 0.235 0.304 15 0.234 0.308 20 0.268 0.406 20.5 0.297 0.406 20 0.291 0.405 25 0.317 0.504 30 0.387 0.574 25 0.341 0.498 30 0.364 0.607 35 0.434 0.678 30 0.397 0.610 35 0.402 0.703 40 0.468 0.755 35 0.432 0.689 40 0.438 0.796 45 0.508 0.866 40 0.472 0.790 45 0.471 0.896 50 0.545 0.966 45 0.608 0.885 00 0.788 ~ oo 0.870 -- 00 0.860 — 00 0.790 — 00 0.875 — oo 0.858 —

0.789 A0o = ^oo ~ 0.873 A co - 0.859 ki - 0.800 k l = 0.775 k l = 0.792 40 40 40 . -1 s 0.0200 m m . = 0.0194 min.“^ — 0.0198 min." k£ " 42.2 l./m.min. = 41.0 l./m.min. = 41.8 l./m.min. 178

TABLE 75

Compound Cycloheptanone Dimethyl Ketal

Temp. -21.13° Date 1-23'-58 Acid conc. 2.65xl0"^(moles/l)

Run 180 Run 181 Run 182

Ketal conc. 0.640 Ketal conc. 0.545 Ketal conc. 0.572 (gms ./l00 mis.) (gms./lOO mis.) (gms ./lOO mis.) Calc. A q = 0.009 Calc. A q “ 0.007 Calc. A 0 = 0.008

Time At A 00-A0 Time At ln A00-A0 Time Afc In A o o ^ o (min. (min.) ) Aoo"”^t A oe"At (min.) Aoo_At

5 0.122 0.153 5 0.106 0.153 5 0.102 0.144 10 0.192 0.263 10 0.167 0.258 10 0.169 0.257 15 0.267 0.394 15 0.232 0.389 15 0.242 0.399 20 0.324 0.507 20 0.291 0.522 20 0.294 0.513 25 0.384 0.640 25 0.342 0.652 25 0.343 0.637 30 0.449 0.806 30 0.376 0.750 30 0.389 0.765 35 0.485 0.916 35 0.413 0.867 35 0.428 0.887 40 0.521 1.04 40 0.449 1.00 40 0.473 1.055 45 0.550 1.15 45 0.476 1.11 45 0.495 1.15 oo 0.801 — 00 0.708 — 00 0.722 — CO 0.802 — CO 0.705 — CO 0.720

■^oo ~ 0.802 A0o ~ 0.707 A q o = 0.721

1.025 k l = 1.04 k l = 1.00 kl = 40 40 40

0.0260 min."* 0.0250 min.“* 0.02566i min."* kg = 9.81 l./m.min. kg = 9.43 l./m.min. k2 = 9.68 l./m.min. 179

TABLE 76

Compound Cyclooctanone Dimethyl Ketal

Temp. 7.92° Date 1-21-58 Acid conc. 2.45x10”^ (moles/l)

Run 186 Run 187 Run 188

Ketal conc. 0.766 Ketal conc. 0.597 Ketal conc. 0.551 (gms./lOO mis.) (gms ,/l00 mis.) (gms./lOO mis.) Calc. Ac = 0.011 Calc, A 0 * 0.008 Calc* A q = 0*008

Time A^ ]_n ôoô Time •H In Aoo"ô Time A^. ■ôo"A o (min.) A -A. (min.) U«in.) a ^-A*. oo t A oo'^t

2.5 0.195 0.296 2.5 0.154 0.294 2.5 0.185 0.406 5 0,554 0.596 5 0.256 0.565 5 0.277 0.715 7.5 0.432 0.880 7.5 0.337 0.850 7.5 0.341 1.00 10 0.508 1.13 10 0.400 1.15 10 0.390 1.29 12.5 0.567 1.48 12.5 0.447 1.445 12.5 0.432 1.63 15 0. 605 1.73 15 0.478 1.71 15 0.453 1.86 17.5 0.636 2.02 17.5 0.503 1.985 17.5 0.475 2.17 20 0.661 2.33 20 0.523 2.275 20 0.498 2.66 22.5 0.676 2.57 22.5 0.536 2.52 22.5 0.502 2.77 oo 0.731 00 0.583 — CO 0.535 — oo 0.731 -- 00 0.580 oo 0.534

A 00 = 0.731 ^ O O - 0.582 ■koo = 0.535 M II 2.31 rH 2.38 k! = k l = 2.38 20 20 20

0.1155 min. - s 0.1190 min.”^ = 0.1190 min. kg = 455 l./m.min. = 485.5 l./m.min. = 485.5 l./m.min. 180

TABLE 77

Compound Cyclooctanone Dimethyl Ketal

Temp. -10.69° Date 1-23-58 Acid conc. 4.75x10"4 (moles/l)

Run 189 Run 190 Run 191

Ketal conc. 0.713 Ketal conc. 0.690 Ketal conc. 0.680 (gms./lOO mis.) (gms,./lOO mis.) (gms./lOO mis.) Calc. A 0 = 0.010 Calc. A q = 0.010 Calc. A 0 ” 0.009

Time A^. -|n A 00-A0 Time At ln A o0~Ao Time A* m ^00-^0 (min.) A00-A^" (min.) Aoo”A^; (min.) k o o " \

5 0.068 0.091 5 0.074 0.105 5 0.072 0.104 10 0.116 0.174 10 0.119 0.182 10 0.113 0.178 15 —.— . 15 0.172 0.285 15 0.159 0.266 20 0.206 0.344 20 0.207 0.358 20 0.204 0.365 25 0.242 0.422 25 0.246 0.448 25 0.236 0.439 30 0.295 0.549 30 0.282 0.536 30 0.273 0.534 35 0.313 0.597 35 0.316 0.531 35 0.311 0.540 40 0,347 0.693 40 0.342 0.709 40 0.336 0.719 45 0.368 0.755 45 0.365 0.784 45 0.361 0.800 oo 0.685 — 00 0.664 -- 00 0.548 — 00 0.685 __ 00 0.664 — 00 0.648 —-

Aoo = 0.685 ^oo = 0.564 Aoo = 0.548

= 0.675 k l k lX = 0.710 k l = 0.712 46 40 40

= 0.01S9 min.""1 = 0.01775 min."1 = 0.0178 min."1

= 35.6 l./m.min. = 37.35 l./m.min. kg - 37.5 1^4.rain. 181

TABLE 78

Compound Cyclooctanone Dimethyl Ketal

Temp. -0.04 0 Date 2-2-58 Acid conc. 2.74x10“^ (moles/l)

Run 192 Run 193 Run 194

Ketal conc. 0.748 Ketal conc. 0.793 Ketal conc. 0.722 (gms ./.OO mis.) (gms ./lOQ mis.) (gms./lOO mis.) Calc. A 0 = 0.010 Calc. A 0 c 0.011 Calc. A 0 = 0.010

Time A* itt A oo“A o Time A-h In A oo"A0 Time A-h in A-oo~’&o (min* ) Aoo”At (min.) Aoo"At (min.)

3 0.099 0.133 3.5 0.111 0.142 3 0.092 0.124 6 0.164 0.241 6 0.174 0.247 6 0.161 0.243 9 0.224 0.351 9 0.233 0.254 9 0.218 0.354 12 0.275 0.458 12 0.289 0.466 12. 0.272 0.470 15 0.324 0.574 15 0.346 0.596 15 0.318 0.582 18.5 0.379 0.717 18 0.385 0.698 18 0.362 0.703 22 0.421 0.842 21 0.429 0.822 21 0.409 0.848 25 0.450 0.940 24 0.469 0.951 24 0.431 0.925 27 0.468 1.005 27 0.498 1.06 27 0.461 1.03 00 0.732 — 00 0.757 — 00 0.710 — oo 0.731 oo 0.757 00 Q.TO6 --

^oo 0.732 A oo — 0.757 A oo 0,708 0.925 0.950 0.942 k l = k l = k l = 24 24 24

= 0.0385 min.”* S 0,0396 min.“* = 0.0393 min. ”*

s 156 l./m.min* = 160.5 l/n.min. - 159.5 l./m.min. 182

TABLE 79

Compound Cyclooctanone Dimethyl Ketal

Temp. -21.12° Date 2-4-58 Acid conc. 2.65x10“® (moles/l)

Run 195 Run 196 Run 197

Ketal conc. 0.511 Ketal conc. 0.501 Ketal conc. 0.514 (gms./lOO mis.) (gms,./lQQ mis.) (gms./lOO mis.) Calc. A0 = 0.007 Calc. A 0 = 0.007 Calc. A0 = 0.007

Time A^. ^ A 0(?A0 Time Afc A o o ~ a g Time Aj. A oo“A 0 (min.) A q q -A); (min.) (min.) A q o -Aj. A oo-At

5 0.067 0.131 5 0.059 0.113 5 0.060 0.113 10 0.098 0.203 10 0.099 0.211 10 0.104 0.219 15 0.135 0.300 15 0.133 0.300 15 0.141 0.316 20 0.174 0.416 20 0,167 0.403 20 0.175 0 . 415 25 0.200 0.498 25 0.199 0.504 25 0.212 0.536 30 0.230 0.602 30 0.226 0.601 30 0.231 0.605 35 0.252 0.689 35 0.251 0.699 35 0.259 0.713 40 0.274 0.780 40 0.273 0.793 40 0.279 0.800 45 0.297 0.888 45 0.293 0.892 45 0.297 0.884 00 0.499 — 00 0.492 — oo 0.501 — 00 0.500 — oo 0.492 — 00 0.501 --

A A q o = 0.500 "oo = 0.492 A q o = 0.501 = 0.790 k l * 0.790 k l = 0.798 k l 40 40 40

= 0.01975 min.“^ = 0.01995 min."-*- = 0.01978 min.”"*'

= 7.45 l./m.min. = 7.53 1^4.min. = 7.46 l./m.min. TABLE 80

Compound Cyclononanone Dimethyl Ketal

Temp. 15.86 Date 5-15-58 Acid conc. 1.218xl0“4 (moles/l)

Run 201 Run 202 Run 203

Ketal conc. 0.351 Ketal conc. 0.351 Ketal conc. 0.325 (gms./lOO mis.) (gms./lOO mis.) (gms./lOO mis.) Calc. A q * 0.013 Calc. A q = 0.013 Calc. A 0 = 0.012

Time A^ ôo~ô Time Aj. Aoo~Ao Time Af. Ao0-Ao (min.) ôo_At (min.) A 00-Afc (min.) A oo-At

5 0.059 0.174 5 0.060 0.187 5 0.057 0.187 10 0.097 0.344 10 0.092 0.333 10 0.090 0.344 15 0.131 0.525 15 0.124 0.510 15 0.118 0.505 21 0.162 0.726 20 0.151 0.685 20 0.417 0.703 25.2 0.181 0.871 25 0.175 0.875 25 0.164 0.836 30 0.196 1.005 30 0.190 1.01 30 0.181 1.00 35 0.213 1.18 35 0.208 1.21 35 0.199 1.195 40 0.235 1.46 40 0.222 1.39 40 0.209 1.33 46 0.239 1.525 45 0.232 1.55 45 0.220 1.495 00 0.302 — CO 0.291 — oo 0.280 — oo 0.302 -- oo 0.290 — oo 0.279 • Ml

0.302 = 0.291 A o o A q o A oo = 0.280

1.34 * 1.39 kl = k l k l = 1.34 40 40 40 n = 0.0335 min.-1 = 0.03475 min."1 = 0.0335 min."J II

K* 275*5 l./m.min. = 285.5 l./m.min. = 275.5 l./m.trd

DO k 2 k2 184 TABLE 81

Compound Cyclononanone Dimethyl Ketal

Temp. -0.03° Date 5-19-58 Aoid cono. 6.49xIQ“4 (moles/l)

Run 204 Run 205 Run 206

Ketal conc. 0.371 Ketal conc. 0.341 Ketal conc. 0.303 (gms./lOO mis.) (gms./lOO mis.) (gms./lOO mis.) Calc. Ac - 0.013 Calc. A 0 = 0.012 Calc. A = 0.011

Time A+ in A oo"A o Time A+. 1* A oo”A o Time A+ Aoo-A*) (min.) (min.) A^-A, (min.) Aoo_At A oo”At

5 0.040 0.095 5 0.044 0.122 5 0.035 0.105 10 0.068 0.199 10.5 0.065 0.207 10 0.058 0.207 15 0.095 0.315 15.3 0.086 0.308 15 0.077 0.307 20 0.116 0.409 20.5 0.107 0.412 20 0.096 0.415 25 0.136 0.515 25 0.124 0.510 25 0 . 1 1 1 0.510 30 0.156 0.629 30 0.142 0.624 30 0.125 0.612 35 0.171 0.727 35.5 0.161 0.756 35 0.141 0.737 40 0.186 0.833 40 0.170 0.829 40 0,152 0.837 45 0.201 0.951 45 0.183 0.940 45 0.165 0.963 oo 0.318 — 00 0.293 m m oo 0.259 — oo 0.320 — 00 0.293 — CD 0.261 —

A 0o = 0.319 A oo 0.293 A oo = 0.260 = 0.837 0.830 = 0.815 k l k l = k l 39. 2 40 40

— 1 * 0.02135 min.”1 = 0.02075 min."1 » 0.0204 min.

= 32.9 l./m.min. 32.0 l/i.min. k2 k 2 = k2 = 31.5 l./m.min 185

TABLE 82

Compound Cyclononanone Dimethyl Ketal

Temp. 7.83 Date 5-23-58 Acid conc. 2.32x10“^ (moles/l)

Hun 207 Run 208 Run 209

Ketal conc* 0.319 Ketal conc. 0.326 Ketal conc. 0.333 (gms./lOO mis* (gins./lOO mis.) (gms./lOO mis.) Calc. A q ~ 0.012 Calc. A 0 - 0.012 Calc. A Q = 0.012

Time A. Time A^. In A °°~A° in A o°"A o Time A^. ôo'ô (min.) (min.) ■ôo"^t (min.) Aoo_At

5 0.040 0.113 5 -- 5 0.041 0.100 10 0.064 0.219 10 0.063 0.218 10 0.066 0.215 15 0.087 0.337 15 0.087 0.340 15 0.093 0.343 20 0.106 0.441 20 0.106 0.448 20 0 . 1 1 1 0.439 25 0.126 0.569 25 0.123 0.554 25 0.132 0.563 30 0.143 0.690 30 0.140 0.675 30 0.149 0.675 35 0.155 0.785 35 0.154 0.783 35 0.161 0.765 40 0.169 0.908 40 0.168 0.912 40 0.175 0.880 45 0.180 1.02 45 0.179 1.05 45 0.184 0.959 oo 0.274 — CO 0.273 — 00 0.290 00 0.275 — oo 0.273 — CO 0.291 -

= 0.275 = 0.273 A = 0.291 o A oo o OO

= 0.902 = 0.906 = 0.880 k l k l k l 40 40 40

- 0.02255 min. - 0.02265 min.-1 = 0.02200 min."1

kg - 97.2 l./m.min. - 97.5 l^n.min. = 94.8 l./m.min. 186

TABLE 83

Compound Cyclodecanone Dimethyl Ketal

Temp. 15.86 ° Date 4-29-58 Acid conc. 2.3Q3xl0”4 (moles/l)

Run 213 Run 214 Run 215

Ketal conc. 0.314 Ketal conc. 0.297 Ketal conc. 0.309 (gms./lOO mis.) (gms./lOO mis.) (gms ./lOQ mis.) Calc. A q ~ 0.016 Calc. A 0 = 0.016 Calc. A q = 0.01 o

Time ^ ln t-oo-K Time A+ i„ Aoo”Ao Time In A 00“A 0- (mm.) (min.) A00"^fc (min.) A oo“At

5 0.053 0.178 5 0.050 0.170 5 0.063 0.231 10 0.081 0.336 10 0.078 0.333 10 0.081 0.336 15 0.103 0.485 15 0.099 0.476 15 0.106 0.506 20.5 0.129 0.690 20 0.123 0.670 20 0.126 0.663 25 0.143 0.820 25 0.143 0.868 25 0.143 0.820 30 0.166 1.08 30 0.150 0.949 30 0.164 1.05 35 0.169 1.12 35 0.162 1.10 35 0.173 1.175 40 0.181 1.30 40 0.176 1.31 40 0.183 1.33 45 0.191 1.47 45 0.183 1.44 45 0.193 1.51 00 0*243 00 0.235 — 00 0.243 — oo 0.243 ~ 00 0.235 m i aw 00 0.243 —

0.243 0.235 A 00 A oo = A oo 0.243 1.31 1.29 1.335 k l “ k l = k± l = 40 40 40 -i ss 0.0328 min. * = 0.0323 min.~^ =0.0333 min.” '*' kg = 142 l./m.min. = 140 1,/r.min = 144.5 l./m.min. 187

TABLE 84

Compound Cyclodecanone Dimethyl Ketal

Temp. 28.12° Date 5-2-58 Acid conc. 1.202x10"4 (moles/l)

Pom 216 Run 217 Run 218

Ketal conc. 0.285 Ketal conc. 0.338 Ketal conc. 0.313 (gms./lOO mis.) (gms •/lOO mis.) (gms ./lOO mis.) Calc. A 0 = 0.021 Calc. A c = 0.025 Calc. A 0 = 0.023

Time At in A oo"A o Time K. 1 n A Oo”A o Time At In Aoo”A° (min.) A 00-i^ (min.) (min.) A oo_At A oo"A t

3 0.0 78 0.223 3 0.092 0.223 3 0.087 0.231 7 0.139 0.537 6 0.148 0.450 6 0.138 0.457 10 0.174 0.770 9 0.195 0.700 9 0.180 0.698 12 0.192 0.916 13 0.238 1.00 12 0.215 0.952 15 0.216 1.15 15 0.258 1.17 15 0.241 1.195 18 0.235 1.39 18 0.281 1.42 18 0.262 1.44 21 0.255 1.72 21 0.297 1.63 21.5 0.280 1.72 24 0.262 1.87 24 0.312 1.89 24 0.289 1.90 27 0.271 2.10 27 0.321 2*08 27 0.300 2.16 CO 0.306 — oo 0.363 00 0.336 — 00 0.306 -- CO 0.363 00 0.336 —

Aoo * 0,306 Aoo = 0.363 Aoo 0.336 = 2.10 k l k l = 2.11 k l = 2.16 27 27 27

= 0.07781 min.”* = 0.0781 min. = 0.0799 min."-

» 646 1./m.rrdn. = 650 1./m.min. it 664 1./m.min. k 2 k2 ro 188

TABLE 85

Compound Cyclodecanone Dimethyl Ketal

Temp. 0.00° Date 5-3-58 Acid conc. 2.595xl0~3 (moles/l)

Run 219 Run 220 Run 221

Ketal conc. 0.490 Ketal conc* 0.415 Ketal oonc. 0.460 (gms./lOO mis.) (gms ./lOO mis.) (gms ./lOO mis.) Calc. A0 = 0.026 Calc. A 0 = 0.022 Calc. A 0 = 0.024

Time ln Time Time At A t I n A oo~A o A t m A ° ? ' ^ (min.) A o o ~ h (min.) A -A. (min.) oo t A o o ”A t

5 0.092 0.215 5 0.079 0.215 5 0.085 0.207 10 0.143 0.420 10 0.126 0.442 10 0.136 0.425 15 0.188 0.638 15 0.159 0.626 15 0.174 0.623 20 0.224 0.860 20 0.191 0.854 20 0.205 0.820 25 0.252 1.07 25 0.215 1.07 25 0.233 1.04 30 0.274 1.29 30 0.236 1.30 30 0.255 1.26 35 0.293 1.51 35 0.252 1.52 35 0.277 1.53 40 0.313 1.81 40 0.271 1.88 40 0.290 1.74 45 0.325 2.05 45 0.280 2.10 45 0.302 1.97 00 0.369 — CO 0.316 — 00 0.347 — 00 0.369 — 00 0.316 — 00 0.347 —

0.369 Aoo A oo 0.316 Aoo ~ 0.347 II 1 IV IV 1.73 1.735 1.67 1— k l = k l = 40 40 40

S 0.0433 min.”1 = 0.0433 min. -1 = 0.0417 min.”1 n IV 16.65 l./m.min. k 2 = 16.65 l./m.min. 16.05 l./m.mir ro k 2 = 189

TABLE 86

Compound. Cyclodecanone Methyl Enol Ether

Temp. 15.86 Date 4-28-58 Acid conc. 1.022x10”^ (moles/l)

Run 225 Run 226 Run 227

Ketal conc. 0.349 Ketal conc. 0.366 Ketal conc. 0.383 (gms./lOO mis.) (gms./lOO mis.) (gms./lOO mis.) Calc. A c = 0.028 Calc. A 0 = 0.029 Calc. A q = 0.030

Time ■ôo'ô Time A^. In ôo”ô ln^£SL Time At In (ndn. ) A (min.) oo (min.) ■^■oo“^t

15 0.106 0.199 Id 0.091 0.149 15 0.096 0.153 30 0.148 0.326 30 0.133 0.265 30 0.141 0.270 45 0.186 0.454 45 0.174 0.395 45 0.180 0.385 60 0.224 0.602 60 0.208 0.516 60 0.218 0.510 75 0.247 0.702 75 0.238 0.636 75 0.251 0.637 90 0.279 0.868 90 0.268 0.775 90 0.278 0.750 105 0.296 0.965 105 0.293 0.904 105 0.301 0.859 120 0.312 1.065 120.5 0.311 1.01 120.5 0.322 0.972 135 0.329 1.19 136.5 0.331 1.14 136 0.341 1.085 00 0.461 — 00 0.472 — oo 0.500 — 00 0.460 — 00 0.473 — 00 0.500 —

■^■00 = 0.461 ■&oo = 0.473 -A-oo “ 0.500 M <( II k l = 1.010 1—1 0.955 0.950 120 120 120

= 0.00840 min.^ = 0.00792 min.”1 - 0.00792 min. ^

k2 = 0.822 l./m.min. = 0.775 l./m.min kg = 0.775 l./m.min. 190

TABLE 87

Compound Cyclodecanone Methyl Enol Ether

Temp. 15.86° Date 4-28-58 Acid conc. 1.022x10"^ (moles/l)

Run 228

Ketal conc. 0.340 (gms./lOO mis.) Calc. A c = 0.027

Time At. In Aoo'A° ‘

(min.) •** o o

10 0.067 0.106 20 0.097 0.191 30 0.122 0.270 40 0.153 0.375 50 0.173 0.448 61 0.193 0.528 70 0.212 0.610 80 0.229 0.693 90 0.243 0.764 00 0.434 — 00 0.430 —

Aoo = 0.432

k l = 0.670 80”

= 0.00838 min."1

= 0.821 l./m.min. 191

TABLE 88

Compound Cyclodecanone Methyl Enol Ether

Temp. 28.12° Date 5-1-58 Acid conc. 1.010x10"^ (moles/l)

Run 229 Run 230

Ketal conc. 0.451 Ketal conc. 0.480 (gms./lOO mis.) (gms./lOO mis.) Calc. Ac = 0.036 Calc. A 0 = 0.038

Time A * In A 00“A O Time A^ nn A oo-Ao (min.) A q q -A,. (min.) Ao;--At

3 0.090 0.105 3 0.099 0.109 6 0.136 0.203 6 0.151 0.215 9 0.1800.307 9 0.199 0.322 12 0.215 0.399 12 0.239 0.419 15 0.246 0.485 15.2 0.275 0.516 18 0.277 0.582 18 0.305 0.606 21 0.307 0.685 21 0.332 0.699 24 0.342 0.825 24 0.360 0.797 27 0.354 0.875 27 0.389 0.912 00 0.584 -- 00 0.626 — oo 0.578 00 0.624 —

0.582 A oo= A oo= 0.625

kl = 0.770 k l = 0.795 24 24

= 0.0321 min."^ = 0.0331 min.”^

k2 = 3.18 1../m.min. k2 = 3.:« i,./m.mir 192

TABLE 89

Compound Cyclodecanone Methyl Enol Ether

Temp. 0.00° Date 5-5-58 Acid conc. 1.04xl0~2 (moles/l)

Run 231 Run 232 Run 233

Ketal conc. 0.555 Ketal conc. 0.473 Ketal conc. 0.525 (gms./lOO mis.) (gms ./lOO mis.) (gms ./lOO mis.) Calc. Ac = 0.044 Calc. A 0 = 0.037 Calc. A0 = 0.041

Time ln Aoo_Ao Time A-fc in A oo-A0 Time At In A°°"A° Crain.) A'oo-At (min.) A oo“‘At (min.) A 00-At

90 0.115 0.109 86 0.096 0.109 86 0.104 0.102 180 0.177 0.219 180 0.154 0.223 180 0.165 0.208 270 0.231 0.322 270 0.198 0.322 270 0.210 0.296 360 0.276 0.416 360 0.240 0.426 360 0.256 0.392 457 0.320 0.519 457 0.278 0.530 450 0.292 0.476 540 0.363 0.631 536 0.310 0.629 532 0.327 0.568 630 0.408 0.764 630 0.348 0.756 630 0.370 0.688 720 0.431 0.837 720 0.367 0.829 720 0.400 0.783 812 0.450 0.905 810 0.396 0.948 810 0.430 0.888 00 0.727 — 00 0.627 — CD 0.705 — oo 0.724 — oo 0.621 -- 00 0.702 —

A oo = 0.726 = 0.624 = 0.703 o A oo o

k l = 0.890 k l = 0.905 k l = 0.870 800 800 806"

= 0.00112 min. = 0.001132 min.- ^ = 0.001090 min."

» 0.107 1.,/m.min. = 0.1088 l/i.min. = 0.1049 l./m.mi k2 k2 k 2 193

TABLE 90

Compound Cyclododecanone Dimethyl Ketal

Temp. 15.96° Date 2-17-58 Acid conc. 3.41x10-3 (moles/l)

Run 237 Run 238 Run 239

Ketal cone* 0.515 Ketal conc. 0.365 Ketal conc. 0.483 (gms./lOO mis.) (gms ./lOQ mis.) (gms »/l00 mis.) Calc. A c = 0.036 Calc. A 0= 0.026 Calc * A c » 0.034

Time At in ^0 0 “^-o Time At 1n A C0-Ao Time i n ^■oo~'^'0 (min.) A00-Afc (min.) Aoo-At (min.) K o - H

5 0.091 0.122 5 0.074 0.148 5 0.086 0.122 10 0.150 0.270 10 0.114 0.293 12 0.157 0.318 15 0.195 0.402 15 0.150 0.441 15 0.185 0.409 20 0.236 0.540 20 0.176 0.566 20 0.224 0.549 25 0.275 0.688 25 0.204 0.717 25 0.263 0.709 30 0.305 0.820 30 0.230 0.880 30 0.293 0.852 35 0.334 0.967 35 0.249 1.02 35 0.317 0.985 40 0.359 1.115 40 0.271 1.20 40 0.340 1.13 45 0.374 1.215 45 0.279 1.30 45 0.355 1.24 00 0.516 — 00 0.374 — CO 0.485 00 0.517 — 00 0.374 — 00 0.486 — II

!*> 0.517 0.374 0 0 Aqo ~ •^00 = 0.486

II 1.165 1.095 k l ~ k l = 1.11 40 40 40

= 0.0273 min. - 1x = 0.0291 min.”'*' = 0.02775 min.'

k 2 - 8.54 l./m.min. - 8.13 l./m.min k2 = 8.00 l./m.min. k2 194

TABLE 91

Compound Cyclododecanone Dimethyl Ketal

Temp* 7.83 Date 2-19-58 Acid conc* 1.031x10"^ (moles/l)

Run 240 Run 241 Run 242

Ketal conc* 0.436 Ketal conc. 0.023 Ketal conc. 0.304 (gms./lOO mis.) (gms./lOO mis.) (gms*/lOO mis.) Calc. A0 = 0.031 Calc. A q = 0.023 Calc. A Q = 0.021

Time Afc ]_n A00-A0 Time A^. ôo*ô Time ^ ôo~ô (min.) •^■oo""'^t (min.) Aoo'^t (min.) - & 00- h

5 0.071 0.105 5 0.061 0.129 5 0.057 0.129 10 0.113 0.203 10 0.089 0.235 10 0.085 0.243 15 0.157 0.382 15 0.121 0.375 15 0.109 0.347 20 0.189 0.498 20 0.145 0.492 20 0.136 0.486 25 0.215 0.613 25 0.167 0.615 25 0.156 0.601 30 0.242 0.743 30 0.189 0.751 30 0.175 0.722 35 0.265 0.871 35 0.206 0.875 35 0.191 0.842 40 0.283 0.981 40 0.225 1.03 40 0.203 0.940 45 0.304 1.13 45 0.236 1.135 45 0.216 1.055 oo 0.434 — 00 0.338 00 0.320 oo 0.433 — oo 0.335 -- oo 0.310

* 0.434 =0.337 A 0o Ago A 0o = 0.320 = 0.995 k l k l =1.000 k l = 0.962 40 40 40

= 0.0249 min."1 =0.0250 min."1 = 0.0241 min.”^

k 2 = 2.415 l./m.min. k 2 =2.425 l./m.min. k2 = 2.34 l./m.mir 195

TABLE 92

Compound. Cyclododecanone Dimethyl Ketal

Temp. 28.16° Date 2-21-58 Acid conc. 6.32xl0“4 (moles/l)

Run 243 Run 244 Run 245

Ketal conc. 0.341 Ketal conc. 0.373 Ketal conc. 0,397 (gms./lOO mis.) (gms./lOO mis.) (gms ,/lQQ mis.) Calc. A Q = 0.024 Calc, A c = 0.026 Calc. A q = 0.028 1 i* o o Time A+ A00-A0 Time o £ 3 Time in Aoo“A ° (min.) A q q -iLij (min.) A o0“At (min.) A q o _At

5 0.080 0.178 5 0.076 0.153 5 0.076 0.136 10 0.120 0.329 10 0.120 0.307 10 0.126 0.300 15 0.159 0.501 15 0.159 0.467 15 0.173 0.483 20 0.189 0.658 20 0.195 0.644 20 0.203 0.615 25 0.215 0.820 25 0.223 0.806 25 0.235 0.785 30 0.234 0.952 30 0.248 0.980 30 0.262 0.955 35 0.247 1.055 35 0.265 1.110 35 0.281 1.09 40 0.264 1.21 40 0,283 1.28 40 0.298 1.23 45 0.278 1.36 45 0.299 1.455 45 0.315 1.40 CO 0.367 — oo 0.382 — 00 0.409 00 0.366 -- CO 0.381 — 00 0.409 —

= 0.367 A q O Aoo = 0.382 Aoo = 0.409 = 1.28 k l = 1.32 k l k l = 1.255 40 40 40

= 0.0330 min."^ = 0.0320 :ni n. = 0.03135i min.

e 52.1 l./m.min. = 50,7 l./m.min. = 49.S l./m.min. 196

TABLE 93

Compound Cyclotetradecanone Dimethyl Ketal

Temp. 15.96° Date 2-17-58 Acid conc. 2.185xl0~3 (moles/l)

Run 249 Run 250 Run 251

Ketal conc. 0.321 Ketal conc. 0.316 Ketal conc. 0.325 (gms./lOO mis.) (gms./lOO mis.) (gms,p/lOO mis.) Calc. A 0 = 0.007 Calo. A c = 0.007 Calc. A 0 = 0.007

Time At in Aoo"Ao Time U. ln A °°"Ao Time A*. A'00-A0 (min.) A 00-At (min.) ■^'Oo"*'^t (min.) Aoo“At

10 0.070 0.251 10 0.065 0.234 10.2 0.067 0.233 20 0.106 0.429 20 0.104 0.429 20.2 0.106 0.419 30 0.134 0.596 30 0.136 0.620 30.2 0.142 0.629 41 0.170 0.858 40 0.163 0.820 40.2 0.167 0.806 50 0.190 1.04 50 0.188 1.045 50.2 0.188 0.985 60 0.206 1.215 60 0.203 1.21 60.2 0.211 1.225 70 0.221 1.41 70 0.217 1.40 70.2 0.225 1.405 80 0.232 1.585 80 0.230 1.61 80.2 0.236 1.57 90 0.241 1.755 90 0.242 1.85 90.2 0.246 1.755 00 0.290 -- 00 0.285 — oo 0.296 — 00 0.290 — 00 0.286 mm oo 0.296 —

= 0.290 A-oo A oo = 0.286 Aoo = 0.296 H O CO = 1.595 = 1.62 k x - • kl k l CO

80 80

- 0.01995 min. = 0.02025i min.”"*- = 0.01975 min.”"^ k 2 = 9.12 l./m.min. k 2 = 9.26 1./m.min. k 2 = 9.04 l./m.min. 197

TABLE 94

Compound Cyclotetradecanone Dimethyl Ketal

Temp. 7.83 Date 2-17-58 Acid conc. 2.205x10“® (moles/l)

Run 252 Run 253 Run 254

Ketal conc. 0.316 Ketal conc. 0.319 Ketal conc. 0.334 (gms./lOO mis.) (gms. /lOO mis.) (gms./lOO mis.) Calc. Ac = 0.007 Calc. A 0 = 0.007 Calc. A 0 = 0.007

Aqq—Aq Time A+ In Time A^ a o q -ô Time A-fc ]_n ôo~ô (min.) ■ôo”^t (min.) A o o ~ H (min.) ^ - A * .

20 0.053 0.178 20 0.036 0.136 20 0.042 0.129 40 0.065 0.231 40 0.066 0.239 40 0.075 0.270 60 0.092 0.359 60 0.088 0.344 60 0.099 0.385 80 0.110 0.455 80 0.109 0.458 80 0.112 0.451 99 0.128 0.560 100 0.125 0.554 100 0.132 0.569 120 0.146 0.680 120 0.142 0.665 120 0.155 0.718 140 0.161 0.791 140 0.160 0.800 140 0.169 0.825 160 0.181 0.960 160 0.172 0.900 160 0.181 0.920 180 0.185 1.00 180 0.185 1.02 180 0.196 1.06 CD 0.291 — 00 0.287 — 00 0.296 — OO 0.290 -- CO 0.287 -- CD 0.296 m m

A oc = 0.291 0.287 0.296 ■ ^o o " ■ ^o o ~

= 0.902 V — 0.905 k x = 0.932 k l “”LJL 160 160 160

= 0.00564 min. - 0.00566 min.“^ = 0.00583 min.“^ k£ = 2.56 l./m.min. kg - 2.57 l./m.min. k2 = 2.64 l./m.min. 198

TABLE 95

Compound Cyclotetradecanone Dimethyl Ketal

Temp. 28. 12° Date 2-22-58 Acid conc. 1.218x10“® (moles/l)

Run 255 Run 256 Run 257

Ketal conc. 0.395 Ketal oonc. 0.359 Ketal conc. 0.367 (gms. /lOO mis.) (gms,,/lO0 mis.) (gms./lOO mis.) Calc. A0 = 0.007 Calc. A q = 0.006 Calc. A0 - 0.007

a D0-a 0 Time At In A °o' Time At Time Afc in A oo"A o “ (min.) A0o'_At (min.) Aoo-Afc (min.) M o ”M

5 0.115 0.368 3 0.068 0.219 3 0.069 0.219 9 0.167 0.610 6 0.110 0.399 6 0.118 0.431 12 0.202 0.811 9 0.151 0.613 9 0.151 0.607 15 0.231 1.015 12 0.180 0.798 12 0.132 0.802 18 0.252 1.195 15 0.205 0.990 15 0.205 0.979 21 0.273 1.42 18 0.225 1.17 18 0.226 1.17 25 0.292 1.67 21 0.241 1.35 21 0.248 1.43 27 0.300 1.80 24 0.258 1.585 24 0.258 1.57 30 0.312 2.03 27 0.265 1.70 27 0.272 1.81 00 0.357 — 00 0.323 — 00 0.324 ... 00 0.358 — 00 0.323 — 03 0.324

= 0.358 0.323 A q o Aoo ” A q o ” 0*324 v. = k-l = 1,69 ~ I 1,58 kl ~ 1, 605 25 24 24 . -1 = 0.0676 min. = 0.0658 min.-^ = 0.0669 min. “■ u = 55.5 l./m.min. JT 54.0 l/n.min. 55.0 l./m.mii k2 ro k2 = AUTOBIOGRAPHY

I, Walter Thomas Relchle, was born in Cleveland,

Ohio, on August 2, 1928, the son of Dr. and Mrs. Herbert

S. Relchle. In June, 1953* the Newark College of Engin eering granted me a degree of Bachelor of Science in Chemical Engineering. After working for the Union

Carbide Corporation from 1953-1955 1 received an edu cational leave of absence which permitted me to enter

the Graduate School of The Ohio State University in

September, 1955* 1 held appointments as Teaching Assist

ant (1955-195?)» Research Fellow of the General Electric

Company (1957-1958), and Predoctoral Fellow of the

National Science Foundation (1958) while completing the

requirements for the degree of Doctor of Philosophy.

199