RATE OF ACETATE EXCHANGE OF ~-NORBORNYL ACETATE A Thesis Presented to The School of Graduate Studies Drake University In Partial Fulfillment of the Requirements for the Degree Master of Arts in Physical Science by Boyd E. Ramsey December, 1970 RATE OF ACETATE EXCHANGE OF !!.Q.-NORBOBNIL ACETATE by Boyd E. Ba.msey Approved by Committee: Cha.irman studies TABLE OF CONTENTS CHAPTER PAGE I. HISTORY AND INTRODUCTION • • • • • • • • • • • •• 1 II. EXPERIMENTAL RESULTS ••••••••••••• •• 21 III. DISCUSSION.................... 36 IV• EXPEBIIVJENTAL.. ••••••••••••••• •• 39 Lead tetraacetate ••• • • • • • • • • • • •• 39 Anhydrous benzene •• ••••••••••• •• 39 ~ydrous pyridine ••••••••••••• •• 39 exo-Norbornyl acetate, First method • • • • • • 40 2-Norcamphanol (Norborneol), First method • •• 41 2-Norcamphanol (Norborneol), Second method. • • 41 (Acetic-l-C 14)anhydride • • • • • • • • • • • • 43 C-14-~-NorbornYl acetate • • • • • • • • • • • 44 Dry acetic acid •••••••••••••• •• 45 standardization of the Karl Fisher Reagent • •• 45 Rate solutions, First method • • • • • • • • •• 46 Rates, First method •••••••••••• •• 47 Recovery of the C-14-acetate, First method. • • 47 Rate solutions, Second method • • • • • • • •• 48 Rates, Second method • • • • • • • • • • • • •• 48 C-14-~-NorborYl acetate detection for the second method • • • • • • • • • • • • • • • • 48 BIBLIOGRAJ?HY • • • • • • • • • • • • • • • • • • • • • • 50 LIST OF TABLES TP~LE PAGE I. Typical Beta Counting Intervals for C-14-~­ Norbornyl Acetate Planchets to Obtain Counts! I~nute Averages for 10 ~linute Periods • • • • • • 32 II. Exchange Rate Constant. kef for Solvolysis of exo­ Norbornyl Acetate in glacial Acetic Acid at 0 150 • • • • • • • • • • • • «I' • • • • • • • • • 34 LIST OF FIGURES FIGURE PAGE 1. The plot of the Polarimetric Rate Constant, k , a vs. the Concentration of Common Salt, (MX) •• • • 4 2. The Effect of the Common Salt, I~, on the Titrimetr1c Rate Constant, kt • • •••••• 4 3. The Special Salt-Effect on the Titrimetr1c Rate Constant, kt • • • • 0 0 • 0 • 0 • • • • o • 7 4. Common Salt Depression of the Titrimetr1c Rate Constant • • • • • • • • • • • • • • • • 0 8 5. Carbonium Ion Configurations . o • • 12 6. The Bridged Non-Class1cal Carbonium-Ion of the Norbornyl System in showing 1-2-6-Carbon Orbital Detail . .. .. 19 ~-Norbornyl 7. The IR spectrum of Acetate • • 0 • • 25 8. The IE Spectrum of exo-Norborneol • 0 . 0 0 · • 25 9. The NoM.R. Spectrum for exo-Norborneol . • 0 . 0 • 26 CHAPTER I HISTORY AND INTRODUCTION The rate of racemization of certain optically active compounds is often taken as the rate of carbonium ion forma­ tion. In solvents of low dielectric constant ionization is observed to exceed the rate of solvolysis. During the 1950's the differences in racemization rates and solvolysis rates for some compounds in various solvents were reported. Employing optically active material, BX. the racemiza­ tion rate constant is determined by following polarimetrically the disappearance of the optical actiVity. The titrimetrio rate constant is based on titration of the acid formed along With the solvolysis product. ROS. An exchange rate constant BX + SOH ------">'> ROS + EX can be obtained by including a radioactive isotope in the leaVing group, X-, of the solvolysis system and following the rate of exchange of the radioactiVity. For some substrates 2 18 1 the 0- equilibration rate has been shown to lead to a better estimate o~ the ionization rate constant than the polarimetric rate constant. 2 The di~ferences seen in the equilibration rate con­ stant, the polarimetric rate constant, and the titrimetric and exchange rate constants for a given substrate are attri­ buted to the eXistance of several rather discrete stages of charge separation a~ter ionization of the substrate during solvolysis. The cation and the anion produced by the ioniza­ tion of the substrates are called the ion-pair. The various stages of charge separation form various ion-pair intermediates. As the charge separation increases by stages the ion-pair of the intermediate experiences increased freedom for motion and increased freedom for interaction with the surrounding medium. 181As an example. a given substrate. ROAc, is synthesized with 0 as the carbonyl oxygen in the acetate group. The oxygen isotopes of the OAc- are assumed to be eqUivalent with respect to th~ formation of the covalent bond with the car­ bonium ion, Ii • of the intermediate in the collapse of the ionized intermediate to covalent ROAc. Mass spectrometry will measure the rate of eqUilibration of the oxygen isotopes in the covalent BOAc. BOC~CHJ ,-- .--~ R+ OC~C-rl;- 0 R~C~CHJ The ionization rate constant is estimated by adding the eqUilibration rate constant to the exchange rate constant. The equilibration rate constant is based on the return to starting material while the exchange rate constant is based on the formation of products. Both eqUilibrated starting material and exchanged products, however, arise from the total ionization of the substrate during solvolysis. 2S. Winstein. Bruce Appel, Ray Baker and Art Dlaz. Ion Pairs in Solvolysi§. and Exchange {London: The Chemical Society. 1965).P'. 12.5. special put'ificat:ion No. 19. J The reaction freedom of the ion-pair at any given in­ termediate stage may allow certain events to take place while restricting others. For instance at a given stage an ion­ pair may experience the freedom of motion for equilibration of equivalent atomic structural components within the ion­ 18 pair, as with O-equilibration, but not enough ~reedom to permit as rapid a racemization of the substrate structure. 1 At another ion-pair intermediate there may be enough freedom for the racemization or rearrangement of the substrate, but not enough freedom for rapid interaction of the ions of the ion-pair with the surrounding medium. The inclusion of salts along with the substrate in the solvent during solvolysis may produce effects which expose the ion-pairs. Following are some salt effects seen during solvolysis of several substrates, in particUlar solvolysis of esters of the arylsulfonic acids, £-toluenesulfonic acid, (HOTs), and £-bromobenzenesulfonic acid, (HOBs), in dry acetic acid, (acetolysis), that demonstrate different ion-pair stages. Common-ion and non-common-ion salt effects observed during solvolysis typically show the linear salt-effect pattern 2 on the polarimetrio rate constant, ka , as seen in Figure 1. is. Winstein and others, Ion Pairs in Solvolysis (Special Publication No. 19: London: The Chemical Society, 1965), pp. 120-129. 2 ~., p. 113. 4 (MX) Figure 1. The plot of the polarimetric rate oonstant. ka , vs. the ooncentration of common salt, (MI). Suoh substrates as exo-norbornyl E-bromobenzenesulfon­ ate, threo-1-methyl-2-phenylpropyl toluene-E-sulfonate and threo-2-methoxyphenyl-1-methYlpropyl-~-bromobenzenesulfonate show the normal shallow linear salt-effect pattern for the titrimetric rate constant, kt , as well as for ka on the inclu­ sion of common-ion salt, MX, during acetolysis. 1 See Figure 2. (I«) Figure 2. The effect of the common salt, MX. on the tltrimetric rate constant, kta 5 It will be noted, however, that the titrimetrlc rate constant while having the normal linear salt-effect pattern is less in value than the polarimetric rate constant. On addition of non-common-ion salt, lithium perchlor­ ate, threo-2-~-methoxyphenyl-I-methylpropylOBs and some other substrates, (C)-(G), show a steep special salt-effect followed (A) i • ~-norbornyl X ~H X ii. exo-norbornyl X (B) threo-l-methyl-2-phenylpropyl OTs H9f<Hc- CH/ '~CH JOTs 3 (c) ~-methoxyphenethYl OTe ( D) 2,4-dimethoxyphenyethyl aBs 6 OCH) (E) 1. 2-an1eyl-l-propyl OTs H~0 /H /C-C"" CH~ I H ) OTe 11. anlsyl-1-methylethyl OTs ~) H,,¥ ~ /C-C"'cH H , ) OTe (F) threo-2-£-methoxyphenyl-1-methylpropyl OBs (threo-)-anlsyl-2-butyl OBs) ?CH) H,,9 /H / C~- f-----CH CH)i 3 OBs /C~ ( G) 1. 4-methoxyphenyl OBs / )"oCR] ~ .~ OBs 11. 4-methoxy-l-methylbutyl OBs (H) E-chlorobenzhydryl chloride 7 by the more shallow normal linear pattern. 1 A typical special- salt effect pattern is shown in the plot in Figure 3. 2 LiCl04 Figure 3. The special salt-effect on the titrimetrlc rate constant, kt • With other systems such as the E-methoxyphenethyl OTs, (e), addition of the common salt results in depression of the J titrimetric rate constant, kt • In Figure 4 the maximum amount of depression is reached at low concentrations, an.d is followed by the normal linear salt-effect pattern seen in the other rate constant VB. salt concentration plots. 1Ibid. , p. 114. 2 w1 bid •• p. 113. 3Ibid • , p. 113. 8 --------#­ nOrIrJa1----sart':;rre-- ct MX depressed k t ( ltlX) Figure 4. Common salt depression of the titrlmetric rate constant. Winstein has employed schemes similar to Scheme 1. 1 in discussing experimental kinetic data in terms of ion-pairs. ~ B.X (I) + X­ ---~'. Product (I) (II) (III) (IV) (v) Scheme 1. Evolving from the covalent starting material. (I). is the intimate or internal ion-pair, (II). The two oppositely charged 10ns are in contact and have no solvent molecules separating them. At this stage rearrangement may take place followed by return to covalent material. or further separation into (III). 1S. Winstein. E. Clippinger. A. H. Feinberg. R. Heck and G. C. Robinson. "Salt Effects and Ion Pairs 1n Solvolysis and Related Reactions. III. Common Rate Depression and Exchange of Anions during Acetolysis," ~. Am. Cheni. 2QQ •• ~ (Jan•• 1956), p. )29. 9 (III) represents the external or solvent separated ion- pair which supposes separation of the two ions and the inter­ positioning of a small number of solvent molecules between them. The two oppositely charged ions are still held together by coulombic attraction.1 Interaction with species in the surrounding medium is more probable at this stage of separa­ tion. Indeed with some substrates, (A), (a, and (F),2 there is eVidence that exchange is rapid at this stage, and that consequently there is little chance for the development of dissociation stages beyond (III). Return to covalent starting material is possible from (III) as it is from all stages of dissociation represented in Scheme 1.