This dissertation has been 64—9286 microfilmed exactly as received SMITH, James Stanley, 1939- BIMOLtECULAR ELIMINATION REACTIONS OF CYCLOPENTYL COMPOUNDS. Iowa State University of Science and Technology Ph.D., 1964 Chemistry, organic University Microfilms, Inc., Ann Arbor, Michigan BIMOLECULAR ELIMINATION REACTIONS OF CYCLOPENTYL COMPOUNDS by James Stanley Smith A Dissertation Submitted to the Graduate Faculty in Partial Fulfillment of The Requirements for the Degree of • DOCTOR OF PHILOSOPHY Major Subject: Organic Chemistry Approved: Signature was redacted for privacy. In Charge of Major JVork Signature was redacted for privacy. Head of Major D Signature was redacted for privacy. Dean e College iowa State University Of Science and Technology Ames, Iowa 196.4 ii TABLE OF CONTENTS Page INTRODUCTION 1 HISTORICAL 3 RESULTS AND DISCUSSION 53 EXPERIMENTAL 106 SUMMARY 241 BIBLIOGRAPHY 243 ACKNOWLEDGMENTS 252 1 INTRODUCTION Preliminary investigations of four basic problems of beta elimination mechanisms are reported in this thesis. 1. The effect of changing the dihedral angle between the beta proton and the leaving group By use of the appro­ priately constituted cis and trans-2-aryicydopentyl and cyclohexyl tosylates, a comparison of the ease of beta elimina­ tion as a function of the dihedral angle was undertaken. Predictions relative to the ease of beta eliminations suggest that a maximum will be approached as the dihedral angle approaches 0° and 180°, whereas a minimum will be expected at 90°. In an effort to investigate the nature of the transi­ tion state the following factors were assessed: relative rates, Hammett rho constants, deuterium isotope and solvent effects. 2. The effect of changing beta hydrogen atom's acidity The contention, that an increase in the beta proton's acidity will shift a concerted mechanism toward a carbanion transition state, was investigated. The relative rates of cis and trans- 2-carbethoxycyclopentyl tosylates were compared with appro­ priate 2-arylcyclopentyl tosylates in order to determine whether cis and trans elimination rates tend to coalesce upon increasing the beta hydrogen's acidity. 3. The relative reactivity of p-toluenesulfonate as a leaving group The relative leaving ability of the tosylate 2 moiety is believed to change with the amount of carbon-oxygen breaking in the transition state. The effect of a secondary alpha carbon atom on the relative leaving group ability in beta eliminations was studied by comparing the relative rates of cyclopentyl tosylate and halides to previously investigated systems containing a primary alpha carbon atom. 4. t-Butoxide-t-butanol as a base-solvent system for beta eliminations Erratic beta elimination reaction rates have stimulated a closer investigation of this base-solvent system. 3 HISTORICAL Beta eliminations are processes in which two atoms or groups are removed from adjacent carbon atoms forming a multiple bond. E.g., i I I I X - C - C - Y • C = C 1 II I I Three principal mechanisms, of beta elimination have been recognized and summarized by Ingold (1) in 1950. Today, an extensive amount of data demands a modification of these original views. The recent review by Bunnet-t (2) states the modern theory. Ingold, Hughes and coworkers (3, 4, 5), Bishop (6), Hine (7) and Skell (8) have discussed thoroughly all but the latest literature concerning this field of elimination chemistry. It is the concern of this thesis to add only recent pertinent data and point out developments in this interesting area of research. The E^ or unimolecular beta elimination mechanism is the heterolytic cleavage of the C - X linkage forming a carbonium ion intermediate in the. rate determining step, which then loses a beta hydrogen to solvent or base molecule. I I - I I 4. I I + . H-C-C-X -X . H-C-C B: _• C = C + BH (2) I I IW I I fl^T I I The Ejçg or carbanion mechanism's rate determining step is the removal of a beta hydrogen by base forming a carbanion intermediate, which in the subsequent step forms olefin with the removal of the leaving group. 4 I I -Il II H - C - C - X B: _ C - C - X C = C + X (3) I I slow f ' fast I ' In Eg or bimoleçular elimination mechanism, the beta proton and leaving group are lost simultaneously under the influence of base. i « i • + H - C - C - X B; B: H C C X—•C — C + BH + X —— I I 11 (4) ' The difference in the three beta-elimination mechanisms is the extent of C - H and C - X bond breaking in the rate determining step. The E^ mechanism in its modern interpre­ tation encompasses the range of transition states from one extreme "nearly E^" to the other "nearly E-^g". The "nearly E^" transition state is a synchronous mechanism approaching a carbonium ion intermediate where the C - X bond breaking is far advanced and the C - H bond is relatively undisturbed. The alpha carbon atom has a high partial positive charge. The "nearly E^g" transition state is analogous to that of "nearly E^" except that it is the C - H bond which is almost broken with the corresponding base-hydrogen bond nearly formed and the C - X bond is only slightly stretched. The beta carbon atom has a high negative partial charge. Between these Eg mechanistic extremes is a "central" transition state. This is the ideal synchronous transition state where the C - X and C - H bonds are half broken and the base-hydrogen bond is half formed. It is noted by Bunnett (2) that even this broad mechanism scheme is not adequate to encompass all of the data. The double bond character of the transition state is not supplied by the mentioned mechanisms and it becomes necessary to add to all the possible transition states a diversity of double bond character. For instance, the "central" Eg mechanism has fifty per cent double bond character. But, the C - X and C - H bonds may be broken to the extent of seventy-five per cent and the transition state would contain more double bond character. The fraction of double bond character can vary from nearly zero to nearly one. Furthermore, the amount of double bond character need not be equal to the amount of C - X or C - H bond breaking.. Partial charges may reside on the alpha or beta carbon atoms instead of being delocalized over the alpha carbon-beta carbon bond. In summary, a beta elimination reaction can be placed into one of three mechanisms. If the reaction is Eg in nature, it can be categorized as either "nearly E^", "central" or "nearly B^CB"• Double bond character ând/or partial charges on the alpha and beta carbon can also be described. Although the double bond character of the transition state is of interest, its influence on product ratios and relative rates of elimination reactions has not been determined. The empirical rules of Hofmann (9) and Saytzeff (10) predict the position of the double bond in unsymmetrical elimination reaction products. The Hofmann rule, "the least 6 substituted olefin is the predominant product from the + + + elimination of onium salts (-NRg, - SRg? -PRg)" has been interpreted by Ingold (1) on the basis of electronic inductive effects. The onium's positive charge acidifies the beta protons and the most acidic proton gives rise to the pre­ dominant product. In contrast, the Saytzeff rule, "the most highly substituted olefin is the predominant product from the elimination of secondary and tertiary halides and esters," has as its product determining factor the stability of the olefinic product. The proton acidity is not pronounced enough to steer the reaction away from the most thermodynamically stable products. In summary, the two types of elimination products can be characterized by the transition state. The Saytzeff elimination has a great deal of double bond character in the transition state whereas the Hofmann reaction has very little (11). Brown (12-17) has reasoned that steric effects of the reactant, leaving group and base cause crowding in the transi­ tion state and Hofmann or Saytzeff products are the result of steric factors. Although this approach is spectacularly different from Ingold's, both views can be rationalized by the double bond character of the transition state. The bulkier the system is, the less stability is gained by having a considerable amount of double bond character in the transition state and therefore, more Hofmann products are realized. Also, it has been noted that poor leaving groups I I B:--H C-C -X I I Eg "central" (large amount of double bond character) 11+ I I + b~ I I &+ I&-I _l I H-Ç-Ç B:—H-C-C- X° B-B --H -H • •'Q-C--—X-C-C—--X B:-HB:-- H •••••C—C-X•••••(_ C-C-X Il II II II E^ Eg "nearly E^" Eg "central" Eg "nearly E^g" E1CB M B î H---C-C----X I I Eg "central" (small amount of double bond character) Figure 1. Transition states of beta elimination reaction mechanisms 8 which acidify the beta protons in the transition state lead to Hofmann products. Ledger and McKenna (18) comparing Ej and Eg products of 7-a-cholestanyl trimethylammonium ion concur with Brown's hypothesis that steric effects determine the product ratios and rates of these elimination reactions. On the other hand, Sauhders (19) and DePuy (20, 21) have shown that Eg rates and product ratios follow a reverse relationship to the steric size of the halogen leaving groups. Along with Banthorpe, Hughes and Ingold (4), Saundefs has contended that polar effects determine the product distribu­ tion with steric control only in extremely hindered cases. Bunnett (2) describes the multiplicity of the Eg transi­ tion state with nine basic factors which are measured by five criteria.