IITTTITI H ITTTTTTTITTTTH HTTTTTTTTTI 3123 01096 7184 TM ram This is to certify that the thesis entitled STUDIES OF THE PROPERTIES. SYNTHESIS, AND STRUCTURE OF SEVERAL CROWN ETHER MODIFIED CHROMOPHORES presented by Houston Slade Brown has been aocepted towards fulfillment of the requirements for Ph.D degree in ChemTStry W Major professor Date August 29, 1979 0-7639 L [B R A R Y Mlelan State 1 Universi ”.45 .‘LJ‘ML Steam a fill. . ., , I 0:13.? '1 ram:- ;.‘ A |I| (in... L. ‘ ‘\ intg" - 1/: OVERDUE FINES: 25¢ per day per item RETURNING LIBRARY MATERIALS: Place in book return to remove charge from circulation records STUDIES OF THE PROPERTIES, SYNTHESIS, AND STRUCTURE OF SEVERAL CROWN ETHER MODIFIED CHROMOPHORES By Houston S. Brown A DISSERTATION Submitted to Michigan State University in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY Department of Chemistry 1979 ABSTRACT STUDIES OF THE PROPERTIES, SYNTHESIS, AND STRUCTURE OF SEVERAL CROHN ETHER MODIFIED CHROMOPHORES By Houston 5. Brown Chapter 1 describes the synthesis of a number of new naphthalene crown ethers in moderate yield from the apprOpriate his: (halomethyl)naphthalenes and polyethylene glycols. The following crowns were synthesized: 2,3-naphtho-l4-crown-4 (15%); 2,3-naphtho-l7-crown-5 (l9%); 2,3-naphtho-20-crown-6 (36%); l,8-naphtho-lS-crown-4 (20%); l,8- naphtho-l8-crown-5 (7%); l,8-naphtho-2l-crown-6 (38%); l,2-naphtho-20- crown-6 (4%); l,5-naphtho-l9-crown-5 (ll%); 1,5-naphtho-22-crown-6 (l4%); 1,4-naphtho-22-crown-6 (9%); and l,3-naphtho-2l-crown-6 (16%). These compounds form a series which is very suitable for the study of naphthalene, as it is perturbed from a specific direction, since the perturber (cation) is situated in the center of the crown ring. The conformational effects of rotation of the ethyleneoxy strand about the naphthalene moiety in the 1,5-naphtho crown have also been investigated. The free energy of rotation for the pentaethyleneoxy strand in l,5- naphtho-ZZ-crown-6 is 6.2 Kcal. while for the tetraethyleneoxy strand in 1,5-naphtho-l9-crown-5, it is greater than 2l Kcal. Houston Slade Brown Chapter 2 investigates the solid state structure of three crown ethers. They are the potassium thiocyanate complex of 2,3-naphtho-20- crown-6, l,8-naphtho-2l-crown-6, and the potassium thiocyanate complex of l,8-naphtho-2l-crown-6. Chapter 3 shows the results of preliminary studies on intramolecular energy transfer in two crown ether modified systems using naphthalene and benzophenone as chromophores. The crown ethers do not have a large effect on these systems. Chapter 4 reveals a new type of crown ether, the ferroceno-crown ether. The crown is capable of "ratcheting" or "squeezing down" on a cation of any size, so long as that cation is smaller than the maximum ring size of the crown. Chapter 5 describes a computer-fluorescence spectrOphotometer interface that has decreased the time required for data-callection and reduction by a factor of 100. The programs described here are listed in Appendix A and Appendix 8. Chapter 6 briefly looks at the synthesis of Farnum gt_al;_of the gypsy moth pheremone, (+)-disparlure. Described here are improvements, additions, and scale-up procedures which have been added to this synthesis. ACKNOWLEDGMENT I wish to thank my wife Elene, not only for the friendship, companionship and love that she has shown throughout our college years, but also for the excellent graphics work that she did for this dissertation. I wish to thank my mother for the loving care with which she raised me, as well as the financial assistance which she and my step father provided. Elene's mother and father are also thanked for their encouragement. Dr. Lynn Sousa was outstanding as a research director. His many hours of consultation will be forever fondly remembered by me. The old members of the Sousa group were fun to learn chemistry with, as well as being good friends. They were Joe Bucher, Mark Johnson, and Jim Larsen. Barb Duhl-Emswiler and John Emswiler were also very good friends, who will be always remembered and often missed. Ross and Chrysa Muenchausen, along with Barb, John, and myself, saw many sunrises from the fifth floor while working on the gypsy moth project. I wish to thank Dr. Eugene Legoff for his friendship and consistently good chemical advice. Dr. Don Farnum (Uncle Don) tremendously helped to organize the way in which I thought about chemistry. Dr. Ring Carde was a pleasure to work with, and a future winner of the Nobel Prize. I wish to thank Dr. Donald Ward for his help and patience in all the crystal structure determinations. Don is also an extraordinary friend and human being. The use of Dr. Harry Eick's PDP8 for 5 years is ii gratefully acknowledged. Finally, I wish to thank the Michigan State University Department of Chemistry, PRF, AND NSF for financial support. To Elene, my mother and father, and Mikal and Aron. iv Table of Contents page CHAPTER I - SYNTHESIS OF CROWNS DESIGNED TO DIRECTIONALLY ORIENT METAL IONS (PERTURBERS) RELATIVE TO A NAPHTHALENE CHROMOPHORE . . 2 IntrOdUCtion. O O O O O O O O O O O O O O O O O O O O O O O O 2 Results and Discussion. . . . . . . . . . . . . . . . . . . . 4 Experimenta] O O O O O O O O O O O O O O O O O C O O O O O O O 20 General procedure for the Synthesis of bLs(bromomethyl)- naphthalenes. O O O O O C O O C O O O O O O O O O O C O O O O 20 Preparation of 2, 3 -b__(bromomethyl)naphthalene. . . . . . . . 2l Preparation ofl 1,4 5-b__(bromomethyl)naphthalene. . . . . . . . 2l Preparation ofl £(bromomethyl)naphthalene. . . . . . . . 2l Preparation of l, 3- bLs(bromomethyl)naphthalene. . . . . . . . 21 Preparation of l-chloromethyl-Z-(bromomethyl)naphthalene. . . 22 Preparation of l,8-bi§(methoxycarbonyl)naphthalene. . . . . . 22 Preparation of l,8-bis(hydroxymethyl)naphthalene. . . . . . . 22 Preparation of l,8-bi§(bromomethyl)naphthalene. . . . . . . . 23 General procedure of the synthesis of the crowns. . . . . . . 23 Preparation of 2,3-naphtho-l4-crown-4 (l) . . . . . . . . . . 23 Preparation of 2,3-naphtho-l7-crown-5 (2) . . . . . . . . . . 24 Preparation of 2,3-naphtho-20-crown-6 (g) . . . . . . . . . . 24 Preparation of l,8-naphtho-lS-crown-4 (g) . . . . . . . . . . 24 Preparation of l,8-naphtho-18-crown-5 (§) . . . . . . . . . . 25 Preparation of l,8-naphtho-2l-crown-6 (Q) . . . . . . . . . . 25 Preparation of 1,2-naphtho-20-crown-6 (Z) . . . . . . . . . . 25 Preparation of l,5-naphtho-l9-crown-5 (§) . . . . . . . . . . 26 V Preparation of l,5-naphtho-22-crown-6 (2) . . . . . . . . . . Preparation of l,4-naphtho-22-crown-6 (l ). . . . . . . . . . Preparation of l,3-naphtho-2l-crown-6 (l_). . . . . . . . . . Preparation of l,4,5,8-tetrakis(methoxycarbonyl)naphthalene (1§_. . . . . . . . . . . . . . . . . . . . . . . . . . . . . Preparation of l,4,5,8-tetrakis(hydroxymethyl)naphthalene (1§_. . . . . . . . . . . . . . . . . . . . . . . . . . . Preparation of l,4,5,8-tetrakis(bromomethyl)naphthalene (l ). Preparation of 3,3',4,4'-tetrakis(methoxycarbonyl)- benzophenone (l8) . . . . . . . . . . . . . . . . . . . . . Preparation of 3,3',4,4'-tetrakis(hydroxymethyl)benzhydrol 19 I O O O O O O O O I O O O O O O O O O O O O O O O O O 0 CHAPTER 2 - SOLID STATE STRUCTURE OF THREE CROWN ETHERS. . Introduction. . . . . . . . . . . . . . . . . . . . . Results and Discussion. . . . . . . . . . . . . . . . Experimental. . . . . . . . . . . . . . . . . . . . . CHAPTER 3 - CROWN ETHER MODIFIED SYSTEMS DESIGNED TO PROBE INTRAMOLECULAR ENERGY TRANSFER (PRELIMINARY STUDIES) . . . Introduction. . . . . . . . . . . . . . . . . . . . . Results and Discussion. . . . . . . . . . . . . . . . Experimenta10 O O O O O O O O O O O O O O O O O O O O O O O 0 Preparation of 2,3:bi§(7-hydroxy-2,S-dioxaheptyl)naphthalene (§§_. . . . . . . . . . . . . . . . . . . . . . . . . . . . . Pre aration of l,8-bj§(7-hydroxy-2,5-dioxaheptyl)naphthalene (§§_. . . . . . . . . . . . . . . . . . . . . . . . . . . . . Preparation of 3,4-dimethylbenzophenone (35). . . . . . . . . Preparation of 2,3-bis(bromomethyl)benzophenone (gg). . . . . Preparation of 9,10-(l',2'-(4'-benzoyl)benzo)-°O,21-(2',3'- naphtho)-l,4,7,l2,lS,l8-hexaoxacyclodocasane (39) . . . . . . vi 26 27 27 27 28 28 29 29 32 32 33 62 66 66 71 84 84 85 85 86 Preparation of 9,lO-(l',2'-(4'-benzoyl)benzo)-20,22-(l',8' naphtho)-l,4,7,l2,l5,18-hexaoxacyclodocasane (33) . . . . . . Preparation of 3,3'-dimethylbenzhydrol (31) . . . . . . . . . Preparation of 3,3'-dimethylbenzophenone (33) . . . . . . . . Preparation of 3',4'-dimethyldesoxybenzoin (33) . . . . . . . Preparation of 2-(3',4'-dimethylphenyl)-l-phenylethanol (39). Preparation of 3,4-dimethylstilbene (£1). . . . . . . . . . . Preparation of 3,4-bi§(bromomethyl)stilbene (£3). . . . . . CHAPTER 4 - SYNTHESIS AND PROPERTIES OF FERROCENO-CROWN ETHERS . IntrOdUCtion. O O I O O O O O O O O O O O O O O O O O O O 0 Results and Discuss-ion. 0 O 0 O O O O O O O O O O O O O O O Experiment610 O O O O O O O O O O O O O O O O O O O O C O 0 Preparation Preparation Preparation Preparation Preparation Preparation CHAPTER 5 - A WORKING MINICOMPUTER of l,l'-ferrocene dicarboxylic acid (13). . . . of l,l'-QL§(methoxycarbonyl)ferrocene (35). . . of l,l'-§L§(hydroxymethyl)ferrocene (£3). . . . of l,l'-ferroceno-18-crown-5 (fig) . . . . . . . of l,l'-ferroceno-lS-crown-4 (£1) . . . . . . . of l,l'-ferroceno-21-crown-6 (33) . . . . . . . IntrOdUCtiOn. O O O O O O O O O O O O O O O O O O O O O O 0 Results and DiSCUSS‘ionO O O O O O O O O O O O O O O O O O 0 Experimental 0 O O O O O O O O O O O O O O O O O O O O O O 0 CHAPTER 6 - SOME STUDIES DIRECTED TOWARDS THE TOTAL SYNTHESIS OF (+)-DISPARLURE . IntrodUCtion. O O O O O O O O O O O O O O O O O O O O O O 0 Results and DiSCUSSion. O O O O O O O O O O I O O O O O O O Experimenta] O O O O O O O O O O O O O I O O O O O O O O O 0 vii SPECTROFLUOROMETER INTERFACE. 87 9O 9O 9O 9T 9T 92 92 93 96 96 96 97 97 98 98 99 99 100 108 109 109 115 120 Preparation of 6-methylheptylbromide (£3) . . . . . . . . Preparation of tert-butyl-6-methylheptylsulfoxide (31). . Preparation of 75,85-2-methyl-8-hydroxyocdecan-7-yl-tert- butyl-sulfoxide (333, cis precursor) and its diastereomer (333), trans precursorT—TS,8R). . . . . . . . . . . . . . Preparation of 7S,BS-Z-methyl-8-hydroxyoctadecan-7-yl- tert-butylsulfide (33, gig precursor) . . . . . . . . . . Preparation of (+)-disparlure (33). . . . . . . . . . . . REFERENCES 0 O O O O O O O O O O O O O O O O O O O O O O O O O APPEATDICES O O O O O O O O O O O O O O O O O O O O O O O O O 0 viii 120 121 122 123 123 126 134 Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure 10. 11. 12. 13. List of Figures page Synthesized naphthalene crown ethers, compounds 1 thrOUQh ll. 0 O O O O O O O O I I O O O O O O O O O O O 5 Low temperature 1H NMR spectra of 1,5-naphtho-22- Crown-6 (2).. o o o o o o o o o o o o c o o o o o c o o 1] High temperature 1H NMR spectra of 1,5-naphtho-19- crown-5 (§)oo o o a o o o o o o o a o o o o o o o o o c 14 Proposed crown ethers _l_2_, _l_3_, L4_, 33, and 31. . . . . . 16 Mass spectrum of l,4,5,8-tetrakis(bromomethyl)— naphtha]ene (.11). O O O O O O O O C O O O O O C O O O O 30 The numbering schemes used for 2,3-naphtho—20-crown—6 complexed with KSCN (39), 1,8-naphtho-21-crown-6 uncomplexed (3) and complexed with KSCN (31). . . . . . 34 The potassium thiocyanate complex of 2,3-naphtho-20- crown-6 viewed with naphthalene in the plane of the page. 0 o o O o o o o o o o o o o c o I o o O o o o o o 39 The potassium thiocyanate complex of 2,3-naphtho-20- crown-6 viewed with the six crown ether oxygen atoms in the plane of the page. . . . . . . . . . . . . . . . 40 Packing diagram for the potassium thiocyanate complex of 2,3-naphtho-20-crown-6 viewed along (0 O 1). . . . . 41 1,8-naphtho-21-crown-6 viewed with naphthalene in the plane of the page. 0 O O O O O O O O O I O O O O O 0 O 50 1,8-naphtho-21-crown-6 viewed with the six crown ether oxygen atoms in the plane of the page. . . . . . 51 Packing diagram of l,8-naphtho-21-crown-6 viewed 610ng (0 1 0). c o a c o o o o c c o c o o o o o o o o 52 The potassium thiocyanate complex of 1,8-naphtho-21— crown-6 viewed with naphthalene in the plane of the page. 0 O O O O O O O O O O O O I O O 0 O O O I O O O O 57 ix Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. The potassium thiocyanate complex of l,8-naphtho-21- crown-6 viewed with the six crown ether oxygen atoms in the plane of the page.. . . . . . . . . . . . Packing diagram for the potassium thiocyanate complex of 1,8-naphtho-21-crown-6 viewed along (0 O 1).. Energy levels of the first excited states of naphthalene and benzophenone.. . . . . . . . . . Phosphorescence spectra of crown 30. Excitation 307 nm. Concentration is l. O x 10'11 M.. . . . . PhOSphorescence spectra of crown 30. Excitation 350 nm. Concentration is l. O x 10'1 M.. . . . . Phosphorescence spectra of crown Excitation 307 nm. Concentration is 1.0 x 1514 M.. . . . . Phosphorescence spectra of crown 31. Excitation 350 nm. Concentration is 1. O x 10- 74 M.. . . . . Excitation spectra of crown 31, observing at 415 Concentration is 1.0 x 10-4 MT'. . . . . . . . . Excitation spectra of crown 31, observing at 560 Concentration is 1.0 x 10' MT'. . . . . . . . . Chemical ionization mass spectrum of crown 3Q, . Chemical ionization mass spectrum of crowm 31, . System for data reduction prior to the computer interface. . . . . . . . . . . . . . . . . . . . Modified synthesis of Farnum et al.. . . . . . . is at is at is at is at nm. 59 6O 68 74 75 76 77 78 79 88 89 101 114 List of Tables page Table l. Interatomic distances and angles for the potassium thiocyanate complex of 2,3-naphtho-20-crown-6. . . . . . 36 Table 2. Torsion angles for the potassium thiocyanate complex of 2,3-naphthO-20-Crown-6.. o a o o o o o o o o o o o o o o 37 Table 3. Least squares planes for the potassium thiocyanate complex of 2,3-naphtho-20-crown-6. . . . . . . . . . . . 38 Table 4. Interatomic distances and angles for l,8-naphtho-21- Cr‘owrh-6O O O O O O O O O O O O O O O O O 0 O O O O O O O 43 Table 5. Torsion angles for l,8-naphtho-21-crown-6. . . . . . . . 46 Table 6. Comparison of some l,8—substituted naphthalene derivatives, and the amount of out of plane distortion by the naphthalene carbons.. . . . . . . . . . . . . . . 48 Table 7. Least squares planes for l,8-naphtho-21-crown-6. . . . . 49 Table 8. Interatomic distances and angles for the potassium thiocyanate complex of l,8-naphtho-21-crown-6. . . . . . 54 Table 9. Torsion angles for the potassium thiocyanate complex of 1,8-naphthO-21-Cr0Wn-6.. a o o c o o o o o o o o o c o o 55 Table 10. Least squares planes for the potassium thiocyanate complex of l,8-naphtho-21-crown-6.. . . . . . . . . . . 56 Table ll. Diffraction data, collection data, and cell parameters. 63 Table 12. Final results from refinement of 3, 33, and 33. . . . . 64 xi STUDIES OF THE PROPERTIES, SYNTHESIS, AND STRUCTURE OF SEVERAL CROWN ETHER MODIFIED CHROMOPHORES CHAPTER 1 Synthesis of Crowns Designed to Directionally Orient Metal Ions (Perturbers) Relative to a Naphthalene Chormophore Introduction Since the first report of crown ethers by C.J. Pederson in 1967,1 interest in synthetic multidentate ligands has continually increased. It is amusing to note that the discovery was accidental. Pederson was originally trying to react mono-THP-catechol with 2,2'- 3i§(chloroethyl)ether. It was the unprotected 3L§;phenol which gave rise to dibenzo-lB-crown-6. on @[ + (CICH2CH2120 1°53“, ”+ OH l/\o oi” ° H m, w The details of this discovery have been published.2 Since the original discovery by Pederson, many crown ethers have been made and studied, and several reviews have appeared.3 The crown ethers usually have the repeating subunit (-CH2-CH2-O-)n. If the ethyleneoxy unit is lengthened by one carbon, the resulting pr0pyleneoxy unit gives rise to a macrocycle which has nowhere near the complexing ability of the ethyleneoxy crown ethers. This difference is 3 attributed to conformational changes which alter complexation ability. Crown ethers have been useful in synthetic organic chemistry, due to their ability to solvate cations, especially in a non-polar solvent. Some of the better known examples of this are solubilization of potassium permanganate in benzene ("purple benzene"),4 solubilization of potassium fluoride in acetonitrile or benzene to form a "naked" fluorine anion,5 and solubiliztion of potassium superoxide in dimethyl sulfoxide to give a reagent capable of performing nucleophilic displacement on alkyl halides (or other good leaving groups such as tosylate) to yield alcohols.6 The use of crown ethers to promote base-catalyzed elimination reactions has been reviewed recently.7 Crown ethers have even been used to solubilize rose bengal, a sensitizer in the photoaddition of singlet oxygen to carbon-carbon double bonds.8 Crown ethers have been used as protective groups for aryl diazonium salts.9 Cram and Cram have described the use of crown ethers as complexing agents for a wide variety of cations ("Host-Guest ).10 Chemistry" Cram et al. have used resolved chiral crown ethers to select cations on the basis of their absolute configuration.11 Crown ethers are well suited for the study of interaction between the complexed cation and functional groups attached to the crown ring. The Sousa group has recently reported on the interaction of the naphthalene system and cations complexed by crowns 3, g) and 2312-16 Some of the studies have focused on the response on naphthalene photoexcited states to complexed and therefore oriented alkali metal 12-14 cations. Other work has investigated field induced n-polarization of naphthalene by an oriented positive mon0pole (complexed cation) using 13 ‘15,16 17 318 C NMR. X-ray studies of 3 and complexed 3, and complexed 4 (all of which are described in Chapter 2) have given some indication of 13c NMR work. crown conformation as has the An interesting conformational effect has also been seen in the 1,5- naphtho crowns (3 and 3). The ethyleneoxy strand in 3_rotates freely around the naphthalene moiety, whereas the barrier for rotation in 3_is very high. Results and Discussion Crown ethers l_through 11 were designed with the specific intent of being able to probe naphthalene from a variety of different directions (see Figure 1). These crown ethers also allow proximity effects to be seen by altering the length of the ethyleneoxy strand, and moving the cation (preturber) closer or further away. There are many examples in the literature of crown ethers and macrocyclic polyethers with 313(methylene)benzene (benzylic) subunits.19 A template effect, which was first reported by Greene,20 was also observed in the preparation of crown ethers derived from the 1,2- 31§(bromomethyl)benzene subunit.19C These crowns were prepared using l,2-3L§(bromomethyl)benzene, the apprOpriate polyethylene glycol, and a suitable metal alkoxide (one which will maximize the template effect based on crown ring size and cation size). The absolute yields of these crowns varied between 1% and 63%, with yields maximized for cation size being 31% to 53%. The yields for these and other benzylic-type crowns are usually substantially lower when l,2-3j§(hydroxymethyl)benzene and the appropriate polyethylene glycol ditosylate are used. Phenolic crown ethers, however, often sucessfully use the ditosylate method with high yields of ring closure, but this is presumably due to the increased K; g) ("g ,0") C9 ,2 Figure l. Synthesized naphthalene crown ethers, compounds 1_ through 1__l_. nucleophilicity of the phenoxide over the benzylic alkoxide. The first synthesis of crowns 3_and 3 used the appropriate 313(hydroxymethyl)naphthalene and pentaethylene glycol ditosylate. These two were stirred together at room temperature with two equivalents of potassium Erbutoxide in tetrahydrofuran with ten percent dimethylformamide. The yields of 3_and 3_after chromatography and careful recrystallization were only 11% and 8%, respectively. The 313(hydroxymethyl)naphthalenes were prepared by displacement with sodium acetate on the apprOpriate 313(bromomethyl)naphthalene to give the corresponding 313(acetoxymethyl)naphthalene, followed by basic hydrolysis to the 313(hydroxymethyl)naphthalene. The use of 333(hydroxymethyl)naphthalenes and the appropriate polyethylene glycol ditosylate not only gave poor yields for crown ring formation reactions, but in all cases except the l,8-derivatives represented two more steps for preparation of the 333(hydroxymethyl)naphthalenes. A much higher yield crown ring closure reaction for 3_and 3_ involved the addition of an equimolar mixture of the appr0priate 313(halomethyl)naphthalene and pentaethylene glycol in dry tetrahydrofuran to a stirred refluxing slurry of potassium 37butoxide in tetrahydrofuran. The yields of 3_and 3_after workup, alumina chromatography, and careful recrystallization were 36% and 38% respectively. The other crown forming reaction yields using the appr0priate l3ig(bromomethyl)naphthalene and polyethylene glycol were: 1, l %; 3, 19%; 3, 20%; 3, 7%; 3, 11%; 3, 14%; _1_Q, 9% and _1__l_, 16%. Crown _7_ was synthesized in 4% yield from l-chloromethyl- 2(bromomethyl)naphthalene, which in turn was prepared from 1- chloromethyl-Z-methyl naphthalene. The method of preparation of the 333(bromomethyl)naphthalenes used N-bromosuccinimide in carbon tetrachloride with catalysis by a sunlamp, which produced both light and heat. Although both light and heat were tried independently, neither gave the reproducible results that the sun lamp gave, indicating that both heat and light are probably needed for this reaction. A previous reaction used in preparation of the dibromide, which involved adding benzoyl peroxide to N-bromosuccinimide in refluxing carbon tetrachloride yielded unpredictable results when this author tried it. One time the reaction gave l,4-dibromo-2,3- dimethylnaphthalene from 2,3-dimethylnaphthalene, instead of the desired product, 2,3-333(bromomethyl)naphthalene. The N-bromosuccinimide must be recrystallized,21 dried in vacuo, and stored in a dry dessicator. Use of N-bromosuccinimide not so treated gave poor yields of brominated product, and required long induction periods. Preparation of l,81313(bromomethyl)naphthalene was by a different method, due to the price of 1,8-dimethylnaphthalene (about $80/g in 1976, currently not commercially available). Instead, 1,8-naphthalic anhydride was used. (CH3 T2504 Although l,8-naphthalic anhydride has been reduced directly to 1,8- 313(hydroxymethyl)naphthalene,22 this procedure was found to give very poor yields. Instead, the anhydride was converted to a diester 23 derivative, using the procedure of Geissman and Morris. This involved a methylation using alcoholic potassium hydroxide and dimethyl sulfate. The yield was about 90%. The 1,8-313(methoxycarbonyl)naphthalene was reduced to the diol in quantitative yield using lithium aluminum 24 hydride. The diol gave l,8-31§(bromomethyl)naphthalene in about 60% yield from the diol using phosphorous tribromide in benzene.22 Most of the crowns pictured are likely to exist in solution as mixtures of rapidly interconverting enantiomeric conformations. An x- 17 ray structure determination of 3. shows it to prefer chiral conformations in the solid state, as do 3)8 and 3)7 when complexed with potassium thiocyanate. As indicated above, the 1,5-crowns (3_and 3) are particularly interesting since interconversion of enantiomeric conformations requires the ethyleneoxy strand to stretch past the naphthalene ring and through an achiral intermediate. The Corey-Pauling-Koltun (CPK) model of crown 3 allows the six oxygen ethyleneoxy strand to slip past the edge of the naphthalene system without much difficulty. Even the CPK model of crown 3_allows its five oxygen ethyleneoxy strand to slip around to the other face of the naphthalene, but just barely. If the CPK model sizes reflect behavior at room temperature, the ethyleneoxy strand of crown 3 should be sweeping around the naphthalene faces slowly, but measureably. Crown 3 might be expected to be "skipping" the strand rapidly. In both crowns 3 and 3, the models show that interconversion of enantiomeric conformations requires that the ethyleneoxy strand free any previously complexed cation. The polyethyleneoxy strand would in effect be wiped free of ions bound by more than two crown oxygens as it passes the edge of the naphthalene ring. Therefore, complexed ions might be expected to slow the turning of the ethyleneoxy strand if the rate of ion decomplexaton is slower than the rate of rope skipping. Experimental evidence of the extent of equilibraton of the l enantiomeric conformations of crowns 3_and 3_is given by the H NMR signa1(s) of the naphthylic hydrogens (HA and HB below). 10 When the ethyleneoxy strand is over a face of the naphthalene ring, one hydrogen (HA) on each naphthalene carbon is directed in the general direction of the peri hydrogen, and the other (H8) is directed out away from the naphthalene system. R0pe skipping would interchange the situations of the A and B hydrogens. The 1H NMR Spectrum of the six oxygen 1,5-crown (3) shows a sharp singlet in the naphthylic region at room temperature. Assuming that HA and HB have different chemical shifts (see below), the ethyleneoxy strand is slipping past the naphthalene ring rapidly, as expected from inspection of CPK models. Since the naphthylic protons are diasteriotopic in all conformations except the achiral intermediate described above, one should be able to see two different protons in the 1H NMR. High resolution low temperature spectra of 3 confirm that the interconversion of enantiomeric conformations is very rapid on the NMR time scale. Figure 2 shows the low temperature 1H NMR Spectra of 3_from -74 °C to -149 °C, with the coalescence temperature being -134 °C (139 K). The separation between the two peaks in the non-coalesced Spectrum (-150 °c) is 178 Hz. 11 —74 -865 ’99 WEE? M: Figure 2. Low temperature 1H NMR Spectra of 1,5-naphtho-22-crown-6 (3). 12 We wanted to find the free energy of activation (AG*) about the SP2-5p3 carbon-carbon bond in this system. At coalescence, 2111 (VA-VB) = 1/2- or T = 1/2/ (211)(vA-\)B) where T = the period (or lifetime) of the exchanging system at coalescence vA-VB = the maximum difference in Hz between peak A and peak 8, i.e. the separation between the two peaks in the non coalesced Spectrum, before the movement inwards towards coalescence is started. Since25 k = (I/h)<1>(e'AGT/RT) where k = exchange rate at coalescence = 1/21 3:: 1.380 x 10'16 erg deg-T h = 6.625 x 10"27 erg sec T = temperature (K) ACT = free energy of activation for rotation 1 mol-1 R = 1.987 cal deg- Rearranging, we get Ae* = -R11n[(k/T)(hA;)J and since k = 1/21 = (n)(vA-VB)//2- the final expression for AG* is 36* = -RT1n[(vA-vB)(nh)/(T§/2)] (1) 13 ACT for 3, using equation (1) , is 6.2 Kcal. The free energy of rotation about the C2-C3 bond in butane is 4 to 6 Kcal. so the rotation of the ethyleneoxy strand around the naphthalene moiety is extremely facile. Alkali metal salts, which are known to be complexed with 3_from 13C NMR and photOphysical measurements,14 do not appear to slow the rate of crown ring rotation at temperatures above -80 °C. A saturated solution of potassium chloride in d6-acetone at -80 °C shows no beginning of 13 decoalescence. Judging from C NMR eXperiments in alcohol at room 16 and the fact temperature showing complexation of 3 with this salt, that lower temperatures increase the complexation constant of this particular crown14, the cation should be complexed under the conditions of the experiment. If decoalescence were starting to take place, one would see a shrinking and widening of the naphthalene proton peak. Unfortunately, the system could not be taken to lower temperatures, since the solubility of the salt was already marginal in acetone. At -150 °C, the crown ether is marginally soluble in dichlorodifluoromethane. In contrast to crown 3, crown 3_with a shorter ethyleneoxy strand shows two diastereotOpic protons at room temperature (25 °C). The five oxygen 1,5-crown (3) has an AB quartet in the naphthylic region of its room temperature NMR spectrum indicating that its equilibration is even slower than predicted from CPK model work. The high temperature 1H NMR Spectra of 3_(Figure 3) Shows no coalescence to be taking place at up to 160 °C. The line broadening at this temperature is probably not real, since the sample could not spin in the heated NMR probe past 55 °C. The 14 |60°C .1 LA) 87 °C 57 °C (Spinning stopped) M6 0C 1 Figure 3. High temperature H NMR specta of 1,5-naphtho-19-crown-5 (3). 15 non-spin conditions will tend to slightly broaden the line. The spearation between peaks of the two diasterotOpic protons is 158 Hz. This implies that the free energy of activation for rotation in 3_is greater than 21 Kcal, making interconversion much more difficult than in 3, InSpection of Corey-Pauling-Koltan models for 3_was very misleading, Since interconversion of enantiomeric forms of 3_appears to be only moderately hindered. There are several other crown ethers which the Sousa group has contemplated making. These crowns involve probing a chromophore from not just one direction, but from several at the same time. Three such crowns are 13, 13, and 13_(see Figure 4). Although crowns 13, 13, and 11_have not been synthesized, some work in preparing the immediate precursors to crowns 13_and 13_has been done. The preparation of l,4,5,8-tetrakis(bromomethyl)naphthalene, the starting material for crown 13, is analogous to that for the preparation of 1,8- 313(bromomethyl)naphthalene but starts instead from commercially available l,4,5,8-naphthalene carboxylic anhydride. 16 (c 1133,50‘4 KOH/Alc. H 0 OH F’Br3 €po H 0 OH 16 12 For crown 13, BDTA24 was converted to the tetraester and reduced to give a pentaol. This pentaol can probably be selectively oxidized to give 3,3',4,4'-tetrakis(hydroxymethyl)benzophenone. In a preliminary experiment, oxidation of the pentaol with 1.1 equivalents of pyridinium chlorochromate yielded a product which produced an infrared peak at 1660 cm'1 (compare with the carbonyl in benzophenone at 1665 cm'l), and 33_ peak near 1690 cm'1 (compare with the carbonyl in benzaldehyde). This indicates oxidation of the middle hydroxyl group occurs preferentially to those on the ends of the molecule. 18 [W wracro, 7 C11202 Another approach to this tetraol would be to first protect the ketone carbonyl, and then reduce the ester functionalities. LiMH4/THF ———--> "30' Preliminary experiments done show that the reaction of 3,3',4,4'- tetrakis(methoxycarbonyl)ben20phenone with ethylene glycol and a trace of acid gave an equivalent of water in a Dean-Stark trap, and a solid product of new melting point. This route is probably preferential to the selective oxidation. Although no work on crown 13 has been done, it should be possible to make the tetrabromide from the known 2,3,6,7- tetramethylnaphthalene27 313_N-bromosuccinimide bromination. A sample of l,4,5,8-tetramethylnaphthalene was successfully brominated to give l,4,5,8-tetrakis(bromomethyl)naphthalene, which was identical to the sample previously prepared.28 The 2,3,6,7-system should be easier to brominate, since it is not as sterically hindered. 19 The problem with crowns 13, 13, and possibly 13_is that a single product will not be obtained when the crown is prepared. Although 13 should be the major product when 1,4,5,8-tetrakis(bromomethyl)- naphthalene is treated with the appropriate polyethylene glycol, there are two other possible products, 33_and 31 (see Figure 4). This mixture of three crowns may be very difficult to separate. Crown 31 exists as two discrete enantiomers. These crowns Should present interesting problems for the future. 20 EXPERIMENTAL General. All melting points are uncorrected. Infrared spectra were recorded on a Perkin-Elmer 237B grating spectrophotometer. The 13C NMR spectra were recorded on a Varian CFT-20 spectrometer with deuterochloroform (1538.2 Hz) as an internal standard. The 1H NMR spectra were taken on a Varian T-60 spectrometer with tetramethylsilane and an internal standard, except high resolution spectra, which were taken on a Bruker WH-180 multinuclear spectrometer, with a 10 mm proton insert. Low temperature Spectra (<-90°C) were taken with 10 mg of crown dissolved in 3 mL dichlorodifluoromethane with 0.3 mL deuteroacetone as a lock solvent, and 0.1 uL tetramethylsilane as an internal standard. High temperature Spectra (>35°C) were taken with 10 mg of crown dissolved in 3 mL d6-dimethylsulfoxide with 0.1 uL tetramethylsilane as an internal standard. The mass Spectra were taken on a Hitachi Perkin- Elmer RMU-6D spectrometer. Tetrahydrofuran was distilled from potassium ben20phenone ketyl immediately before use. All reactions were done under nitrogen. Microanalyses were performed by Chemalytics, Inc., Tempe, Arizona, or Instranal Laboratory, Rensselaer, N.Y. General Procedure for the Synthesis of bis(3:9momethyl)naphthalenes. Dimethyl naphthalene (10.0 g, 64.0 mmol) and recrystallized N- bromosuccinimidew (46.0 g, 258 mol) in 250 mL of carbon tetrachloride was irradiated with a 200 watt sun lamp. The reaction was greater than 90% complete (1H NMR) in less than 30 min after noticable conversion of the N-bromosuccinimide to succinimide started. The induction period was 21 highly variable. The mixture was filtered, and the succinimide was extracted with hot carbon tetrachloride. Some of the dibromides were exceedingly soluble in carbon tetrachloride (e.g. the 2,3- 31§(bromomethy1)naphthalene), but others (e.g. 1,4 and 1,5) required multiple extractions to withdraw all of the brominated product from the succinimide. The combined filtrate and extracts were evaporated to give 72-81% yield of the dibromide. The dibromides could be recrystallized from benzene - petroleum ether to remove traces of mono-brominated and starting material. Preparation of 2,3-bis(bromomethy1)naphthalene. Prepared as described above, 81% yield; m.p. 145-146°C; 1 13 H NMR (CDC13) 6 4.77 (s, 4 H), 7.15- 7.7 (br.m, 6 H); C NMR (CDC1 6 30.88, 127.08, 127.60, 130.63, 3) 133.19, 133.66. Preparation of 1,4-bis(bromomethyl)naphthalene. Prepared as described above, 72% yield; mp 190-191°C; T 13 H NMR (coc13) 6 4.83 (s, 4 H), 7.3-8.1 (br.m. 6 H); c NMR (CDCl 6 31.05, 124.50, 126.76, 127.14, 131.53, 3) 134.85. Prgparation of 1,5-bis(bromomethy1)naphthalene. Prepared as described above, 78% yield; mp 213.5-214°c; 1H NMR (CDC13) 6 4.87 (s, 4 H), 7.1- 8.3 (br.m, 6 H); ‘30 NMR (CDC1 6 31.46, 125.29, 125.94, 128.03, 3) 134.08. Preparation of l,3-bis(bromomethyl)naphthalene. Prepared as described above, 76% yield; mp 116-116.5°C; T 13 H NMR (CDC13) 6 4.50 (s, 2 H), 4.77 (s. 2 H). 7.2-8.1 (br.m, 6 H); C NMR (CDC13) 6 30.86, 33.10, 123.53, 126.65, 127.06, 128.29, 128.75, 129.25, 130.51, 133.68, 134.11, 134.46. 22 Preparation of l-chloromethyl-Z-(bromomethyl)naphthalene. Prepared as described above, except that l-chloromethy1-2-methylnaphthalene was 1 used, 78% yield; mp 130-l3l.5°C; H NMR (CDC1 13 3) 6 4.83 (s, 2 H), 5.08 (s, 2 H), 7.08-8.07 (br.m, 6 H); C NMR (CDC1 6 30.52, 37.99, 123.48, 3) 126.47, 127.21, 127.49, 128.59, 129.93, 131.50, 131.65, 133.60, 134.45. Preparation of 1,8-bis(methoxycarbonyl)naphthalene. The dimethyl ester of l,8-naphthalene dicarboxylic acid was prepared by the method of 23 from the 1,8-naphthalic anhydride (Aldrich). 1 Geissman and Morris Spectral data were as follows: 13 H NMR (CDC13) 6 3.85 (S, 6H), 7.2-8.0 (br.m. 6 H); c NMR (CDC1 6 51.77, 125.01, 129.55, 129.94, 132.17, 3) 134.03, 168.94. ngparation of l,8-bis(hydroxymethy1)naphthalene. To 40.0 g (0.164 mol, 2 equiv) 1,8-31§(methoxycarbonyl)naphthalene in l L THF was cautiously added 20.0 g (0.528 mol, 3.2 equiv) lithium aluminum hydride (Alfa- Ventron) under a dry nitrogen atmosphere. The lithium aluminum hydride was added at such a rate that reflux was not vigorous. The reaction was allowed to stir for 8 H. Water (20 mL), 15% sodium hydroxide (20 mL), 24 Initial and then water again (60 mL) were added over a 2 h period. addition of water should be slow, and the nitrogen flow should be fast. The resulting white granular precipitate was filtered and washed with an additional 250 mL THF. The solvent was removed from the filtrate under reduced pressure, and the resulting solid recrystallized from methanol, 98% yield; m.p. 156-157 °c; T H NMR (CDC13) 6 3.30 (s, 1H, disappears with 020), 5.13 (s, 2H), 7.25-7.90 (m, 3H); 130 NMR (c0013) 6 63.80, 124.96, 129.10, 130.15, 135.18, 138.54. 23 Prgparation of 1,8-bis(bromomethyl)naphthalene. l,8-31§(hydroxymethyl)- naphthalene was brominated by the method of Bergman and Szmuszkoviczzz, to give 1,8-31§(bromomethyl)-naphthalene: mp 130-131°C; 1H NMR (CDC13) 6 13 5.22 (s,4 H), 7.20-7.80 (br.m, 6 H); C NMR (CDC1 6 35.43, 123.91, 3) 127.27, 130.11, 131.26, 131.63, 134.30. General Procedure for the Synthesis of the Crowns. A solution of the appropriate polyethylene glycol (10 mmol) and 313(halomethyl)- naphthalene (10 mmol) in 150 mL dry THF was added dropwise to a refluxing tetrahydrofuran slurry of potassium E-butoxide (2.36 g, 21 mmol in 500 mL THF) over a six h period under a dry nitrogen atmosphere. The slurry was stirred at reflux another four h before filtration through a diatomatious earth pad, and subsequent washing of the solid with tetrahydrofuran. Solvent was removed from the filtrate under vacuum, and the resulting yellow oil was chromatographed on a quartz 29 added) column with alumina (400 g, Fisher neutral alumina with Lumilux eluted with dichloromethane-methanol (200:1). The first band eluted which was observable on the column using a 375 nm lamp gave a yellow- brown oil. Some of the fractions of this band crystallize from ether- pentane, and can be recrystallized from cyclohexane except as otherwise noted. Preparation of 3,3-n3phtho-14-crown-4 (1). Prepared as above except that lithium E-butoxide (1.67 g, 21 mmol) and triethylene glycol (1.449, 10 mmol) were used: (460 mg, 15.2%); mp 86.0-88.0 °C; 1 H NMR (coc13) 6 3.60 (s, 4 H), 3.73 (s, 8 H), 4.87 (s, 4 H), 7.13-7.68 (br.m, 6 H); ‘3c NMR (CDC13) 6 69.27, 70.00, 71.37, 71.46, 125.72, 127.46, 132.83, 24 134.89; IR(CHC13) cm”1 3000, 2850 (s), 1550, 1450, 1350, 1300, 1250, 1125 (s), 1025 (w), 975, 925, 900, 875, 800; m/3_302. Anal. Calcd for C18H2204: C, 71.50; H, 7.33. Found: C, 71.77; H, 7.400 Preparation of 2,3-naphtho-l7-crown-5 (3). Prepared as above except that lithium L-butoxide (1.67 g, 21 mmol) and tetraethylene glycol (1.67 1 g, 10 mmol) were used: 652 mg (18.8%); mp 51.0-53.0 °C; H NMR (CDC13) 6 3.58 (s, 10 H), 3.70 (s, 10 H), 4.8 (s, 4H), 7.15-7.73 (br.m, 6 H); 13 C NMR (CDC1 6 69.69, 70.43, 70.71, 70.96, 71.14, 125.71, 126.85, 1 3) 127.44, 132.63, 134.69; IR (CDC13) cm- 2850 (s), 1550, 1450, 1350, 1300, 1250 (w), 1100 (s), 980, 950, 890, 810 (s); m/3_346. H 0 ° C, 69.34; H, 7.57. Found: C, 69.58; Anal. Calcd for C20 26 5. H, 7.36. Preparation of 2,3-naphtho-20-crown-6 (3). Prepared as above except that pentaethylene glycol (2.39 g, 10 mmol) was used: 1.39 g (35.6%); mp 58.0-58.5 °C; 1H NMR (CDC1 6 3.63 (s, 12 H), 3.68 (s, 8H), 4.78 (s, 3) 4H), 7.13-7.77 (br.m, 6H); ‘3c NMR (CDC13) 6 69.80, 70.67, 71.31, 125.72, 127.35, 127.57, 132.63, 134.55; IR (CHCl cm" 3000, 2850-2025 3) (s), 1470 (w), 1450 (w), 1350, 1075-1150 (s); m/g_39o. Anal. Calcd for C22H3006: C, 67.67; H, 7.74. Found: C, 67.65; H, 7.89. Preparation of 1,8-n3phtho-15-crown-4 (3). Prepared as above except that lithium t-butoxide (1.67 g, 21 mmol) and triethylene glycol (1.44 1 g, 10 mmol) were used: 619 mg (20.5%); mp 77.0-77.5 °C; H NMR (CDC13) 6 3.62 (S, 4 H), 3.80 (s, 8 H), 5.17 (s, 4 H), 7.28-7.77 (br.m, 6 H); 25 136 NMR (CDC13) 6 69.74, 70.19. 71.09, 73.13, 124.79, 128.17, 129.43, 134.74, 135.33; IR (CHC13) cm" 3010, 2860 (s), 1600 (w), 1450, 1350, 1290, 1240. 1100, 1000 (w), 960, 940, 875, 800 (s); 3/g_3o2. Anal. Calcd for C18H2204: C, 71.50; H, 7.33. Found: C, 71.72; H, 7.47. Preparation of 1,8-naphtho-l8-crown-5 (3). Prepared as above except that lithium t-butoxide (1.67 g, 21 mmol) and tetraethylene glycol (1.94 g, 10 mmol) were used; 239 mg (6.9%); mp 69.5-7o.o °C; 1H NMR (CDC1 6 3) 3.60 (s, 10 H), 3.72 (s, 10 H), 5.03 (s, 4 H), 7.22-7.70 (br.m., 6 H); ‘30 NMR (c0013) 6 70.00, 70.19, 70.66, 77.16, 124.73, 129.01, 129.68, -1 130.69, 134.21; IR (CHC13) cm 3000, 2850, 1720 (w), 1600 (w), 1450, 1350, 1300, 1250 (w), 1100 (s), 1000, 940 (w), 880, 800 (s); m/§_346. Anal. Calcd for C H 0 20 26 c, 69-34; H. 7.57. Found: c, 69.49; S: H, 7.47. Preparation of 1,8-naphtho-21-crown-6 (3). Prepared as above except that pentaethylene glycol (2.39 g, 10 mmol) was used: 1.50 g (38.4%); mp 1 53.5-55.5 °C; H NMR (CDC13) 6 3.73 (s, 12 H), 3.78 (s, 8 H), 5.17 (s, 4 13 H), 7.35-7.87 (br.m, 6 H); C NMR (CDC1 6 69.30, 70.43, 70.58, 3) 124.62, 129.90, 130.19, 131.11, 133.91, 135.51; IR (CHC13) cm" 3050 (w), 1460, 1350, 1125 (s), 1090 (s), 840, 820; m/2_390. Anal. Calcd for C C, 67.67; H, 7.74. Found: C, 67.77; 22H3006‘ H, 7.79. Preparation of 1,3-naphtho-20-crown-6 (1). Prepared as above except that pentaethylene glycol (2.39 g, 10 mmol) and l-chloromethyl-Z- (bromomethy1)naphthalene (2.70 g, 10 mmol) were used: 172 mg (4.4%); mp 26 1 58.0-58.5 °C; H NMR (CDC13) 6 3.62 (s, 12 H), 3.65 (s, 8 H), 4.44 (s, 2 H), 5.05 (s, 2 H), 7.33-8.22 (br.m, 6 H); 136 NMR (CDC1 6 124.69, 3) 125.49, 126.16, 127.23, 127.89, 128.11, 128.47, 132.16, 133.16, 133.39, 135.06; IR (CDC13) cm'1 3000, 2860 (s), 1460, 1450, 1350, 1300, 1250, 1100 (S), 815; m/3_390. Anal. Calcd for C22H3006: C, 67.67; H, 7.74. Found: C, 67.84; H, 7.79. Prepgration of 1,5-naphtho-l9-crown-5 (3). Prepared as above except that tetraethylene glycol (1.94 g, 10 mmol) and lithium t-butoxide (1.67 g, 21 mmol) were used: 391 mg (11.3% after molecular distillation (110°C 1 at 0.05 mm Hg)); H NMR (CDC1 6 3.35 (S, 2H), 3.42 (s, 2H), 3.45 (s, 3) 2H), 3.52 (s, 2H), 4.83 (dd, 4H, JAB=12 Hz, d separated by 1.00 ppm), 13 7.1-7.4 (br.m, 4H), 7.7-8.1 (br.m, 2H); C NMR (CDC1 6 68.87, 69.53, 3) 69.76, 69.96, 71.81, 124.77, 125.33, 127.25, 132.35. 134.07; IR (neat) cm" 3075 (w), 3050 (w), 3025 (w), 1750, 1710 (w), 1600 (w), 1540. 1460, 1360, 1300, 1250, 1110 (S), 1050, 950, 875, 800(5); m/g_346. Anal. Calcd for C20H2605: C, 69.34; H, 7.57. Found: C, 69.73; H, 7.61. Prepgration of 1,5-naphtho-22-crown-6 (3). Prepared as above except that pentaethylene glycol (2.39 g, 10 mmol) was used; 544 mg (14.2%) yield; mp 55.0-56.0 °C; 1H NMR (CDC1 ) 6 3.08 (s, 4 H), 3.25 (s, 8 H), 3.52 (s. 3 8 H), 4.70 (5, 4h), 7.37-8.10 (br.m, 6 H); 136 NMR (6061 6 68.75, 3) 69.69, 70.00, 70.21, 71.64, 124.90, 126.68. 132.00, 134.04; IR (CHC13) cm" 2975, 2945 (s), 2900 (s), 2865 (s), 1500, 1405, 1290, 1175 (s), 1110, 1035, 825; m/g_390. Anal. Calcd for C : C, 67.67, H, 7.74. Found: C, 67.87; 22H3006 27 H, 7.71. Prgparation of 1,4-naphtho-22-crown-6 (1_). Prepared as above except that pentaethylene glycol (2.39 g, 10 mmol) was used; 359 mg (9.2%) yield; mp 71.5-72.5 °C; 1 H NMR (CDC13) 6 3.37 (s, 4 H), 3.42 (s, 8 H), 3.60 (s, 8 H), 4.97 (s, 4h), 7.1-8.2 (br.m, 6 H); 136 NMR (CDC13) 6 69.99, 70.46, 70.55, 70.75. 124.07, 125.15, 125.48, 131.40, 133.61; IR (CHC13) cm“1 2990, 2850 (s), 1600 (w) 1460 (w), 1350, 1300 (w), 1100 (S), 975, 870, 800 (S); m/g_390. 33311_ Calcd for C22H3006: C, 67.67, H, 7.74. Found: C, 67.72; H, 7.540 Prepartion of l,3-naphtho-21-crown-6 (11). Prepared as above except that pentaethylene glycol (2.39 g, 10 mmol) was used; 632 mg (16.2% after molecular distillation (120°C at 0.05 Hg)); 1H NMR (CDC13) 6 3.60 (S, 12 H), 3.65 (s, 8 H), 4.63 (s, 2 H), 4.97 (S, 2 H), 7.30-7.98 (br.m, 6 H); 13 C NMR (CDC1 6 69.21, 69.50, 69.79, 70.09, 70.48, 70.69, 71.13, 3) 73.25, 123.32, 125.71, 125.83, 126.22, 126.58, 126.80, 128.30, 133.41, 134.08, 135.25; IR (CHC13) cm"1 3000, 2860 (s), 1700, 1450, 1350, 1290, 1240, 1100 (s), 940, 875, 800; m/§_390. 0 Anal. Calcd for C C, 67.67, H, 7.74. Found: C, 67.41; 22H30 6‘ H9 7.63. Preparation of l,4,5,8-tetrakis(methoxycarbonyl)ngphtha1ene (13). To a solution of l,4,5,8-naphtha1ene tetracarboxylic dianhydride (93 g, 0.35 mol) in 670 mL 2.0 N ethanolic KOH was added dimethyl sulfate (373 mL, 3.45 mol) and concurrently 1330 mL 2.0 N ethanolic KOH in a dropwise fashion. The reaction was done at 0 °C, with mechanical stirring, and 28 under nitrogen. After 12 to 16 hours, the solvent was removed under reduced pressure, and the resulting sludge extracted several times by boiling in methanol and decantation. The methanol was diluted with an equal amount of water, and upon cooling gave 12.3 9 crystals, 10% yield; (methoxycarbonyl)naphthalene mp l96-197.5 °C; 1 H NMR (CDC13) 6 3.87 (s, 12H), 7.92 (s, 4H); 136 NMR (CDC13) 6 52.33, 128.97, 133.16, 168.09; IR (Nujol) cm" 1715, 1280, 1200, 1160(w), 1110(w), 855, 750, 720; m/g_360. Preparation of l,4,5,8-tetrakis(hydroxymethy1)naphthalene (13). To a solution of lithium aluminum hydride (30.0 g, 0.79 mol) in 750 mL THF under nitrogen was added tetraester 13 (71.6 g, 0.199 mol) in 750 mL THF in a dr0pwise fashion over a 2 hour period. After 12 hours additional stirring, water (30 mL), 15% NaOH (30 mL), and water (90 mL) were added. After 4 additional hours of stirring, the pure white mixture was filtered, the solvent removed under reduced pressure, and the resulting solid, recrystallized in methanol and water, to give 12.8 g of a light 1 brown solid, 26% yield; mp 130-132 °C; H NMR (d -DMSO) 6 3.30 (s, 4H, 6 exchangeable with 02 ), 5.00 (s,8H), 7.43 (s, 4H); 136 NMR (CD300) 6 64.30, 127.32, 182.21, 188.70; IR (Nujol) cm" 3300, 3200, 1460, 1375, 1295(w), 1055, 100, 845(w); m/3_248. Preparation of l,4,5,8-tetrakis(bromomethyl)naphthalene (11). To a 70 °C solution of 13 (2,5 g, 10 mmol) in 300 mL benzene containing 0.2 mL pyridine was added phosphorous tribromide (3.2 mL, 20 mmol) at such a rate that the temperature of the reaction did not exceed 74 °C. After an additional 2 hours at 55 °C, followed by cooling, the solution was washed with water (3 x 100 mL), then washed with saturated bicarbonate solution (2 x 100 mL), and the benzene layer dried over magnesium 29 sulfate. After removal of the solvent under reduced pressure, the residue was recrystallized from benzene-petroleum ether to give 250 mg 1 1Z_as a white solid, 5% yield; mp 107-109 °C; H NMR (CC14) 6 4.77 (s, 8H), 7.17 (s, 4H); m/3_- see Figure 5. Preparation of 3,4,3',4'-tetrakis(methoxycarbonyl)ben20phenone (13). To a solution of 3,3',4,4'-benzophenonetetracarboxylic dianhydride (93.0 g, 0.29 mol) in 2.0 N ethanolic KOH (670 mL) was added dimethyl sulfate (373 mL, 3.45 mol) and concurrently 2.0 N ethanolic KOH (1330 mL) in a dropwise fashion. The reaction was done at 0 °C, with mechanical stirring, and under nitrogen. After 12 to 16 hours, the solution was filtered, warmed, and water added until the solution just started to turn milky. After cooling, 62.1 g of crystalline 13_were collected, 52% yield; mp 84-86 °C; T 13 H NMR (CDC13) 6 3.87 (s, 1H), 3.90 (s, 1H), 7.6-8.3 (br.m, 1H); C NMR (CDC13) 6 59.00, 130.35, 131.87, 132.41, 136.19, 1 138.63, 166.64, 167.43, 193.09; IR (Nujol) cm' 1740(5), 1660, 1480(w), 1395(w), 1280(5), 1260, 1240, 1120, 1060, 990(w), 940; m/g_414. Prgparation of 3,4,3',4'-tetrakis(hydroxymethy1)benzhygrol (13). To a solution of lithium aluminum hydride (30.0 g, 0.79 mol) in 750 mL THF under nitrogen was added tetraester 13 (40.9 g, 99 mmol) in 750 mL THF in a dropwise fashion. The tetraester was added at such a rate that a steady reflux was maintained. After addition was complete, the solution was gently refluxed for 12 hours. Water (30 mL), 15 % NaOH (30 mL), and water (90 mL) were then slowly added. After 4 hours of stirring, the pure white mixture was filtered, and the filtrate concentrated under reduced pressure, to give 23.8 9 solid 13, 79% yield (note: on one of the runs, 13_was held by the lithium salts. It was necessary to grind 30 ”C183 .2: 0:32.232.afiogasocflmiabouimfié.P mo .5533 mun: .m «.53... 6 0 u 01 0|. 2.. U :0 T I - T1TI TT -1411 1 -TITII. 41.111 T r. S S “I - 1 7L 78 I T 3 S T - .1 11. T S S. m; 3.. S 1 1 I -TT.I.H,.T,m.. S S 5 2.. 2 ”I. 3 51 S S S S ” QM; Q“ .iL M3 M151 T m m n. 2. u. u .6 a. 23 u. S 5 a. “a. w: T - T- T 1-.. o O .nkTiTTT TT. 3 4T 4TT.TT 1. _ a 4 i 4 4 TIT . W 1. 1.1111111 .‘. .0... O... z... v0.0 .3 e. no... I... M... 6,: . .0... O... a... 3.. V... a... a... e... o pmnx Im~OIq anz Imgoxa mez IMHO-Z 3l the salts and continuously extract with THF to free lg from the salts); mp 150-152 °C; 1H NMR (c0300, external TMS) 5 4.23 (s, 4H). 4.37 (s. 4H), 4.0-4.8 (br.m, 5H, dissappear with 020), 5.37 (s, lH), 6.7-7.2 13 (br.m, 6H); C NMR (d -DMSO) 6 60.54, 60.69, 74.55, 124.59, 125.1l, 6 l26.95, l37.83, 139.25, 144.33; IR (Nujol) cm“ 3000-3500 (s), 1150 (w), lll5 (w), l040, l025, 990; m/g_304. Chapter 2 Solid State Structure of Three Crown Ethers Introduction Interest in the crystal structures of macrocyclic polyethers has increased in recent years, as evidenced by the large number of 30 The interest in structures done on synthetic and natural macrocycles. these compounds centers about their ability to surround many different cations. This usually involves a planar coordination geometry for the smaller crowns (e.g. the complex of sodium bromide and dibenzo-lB-crown- 6) and a cage for the larger crowns and crypts (e.g. the potassium 3] The sorts of information iodide complex with dibenzo-BO-crown-lO). which can be derived from these structures includes the following: l) The type of the coordination which occurs between the ligand and the cation can be elucidated by investigation of such factors as size of cation, ligand size, and solvent effects. 2) Conformational changes which are necessary for a free ligand to complex different sized cations can be examined. This can be striking. In order for 30-crown-l0 to form a complex with potassium thiocyanate, only jou£_bonds need to be twisted.32 3) The actual size of the cavity in the free ligand can be determined, which can give an accurate estimate of complexation ability. 4) One can examine the interaction between molecules of solvent and the cation, as well as the overall effect that this cation solvation has on the ligand complexation by the crown ligand. 5) The effect which counterions have on the packing of the unit cell 32 33 as well as general symmetry of the molecule. This section of the dissertation will discuss three structures which have been determined, and will focus on their similarities to, and differences from, those already in the literature. The relevence of these structures to some of the other work which has been undertaken in the L.R. Sousa group will also be discussed. Results and Discussion The crystal structure determination of the potassium thiocyanate complex of 2,3-naphtho-20-crown-6 (22) was undertaken because it seemed lSa,33 likely that the conformation of the crystalline complex would closely resemble the most probable conformation(s) in a solution or glass. The numbering scheme for gg_is shown in Figure 6.34 A major structural feature is the twofold axis present in the molecule. The potassium ion lies on this twofold rotation axis. The thiocyanate ion is disordered and lies accross the twofold axis, while the naphtho-crown ligand is also related, one half to the other, by this axis. The six crown ether oxygen atoms, which all coordinate to the potassium ion, lie within 10.35 3 of the best plane containing the oxygen atoms and the potassium ion, as well as the twofold rotation axis. The potasium ion is 6.97 3 from the center of the naphthalene ring (midpoint of the C3-C3a bond), and 4.52 K from the end (midpoint of the C5-C5a bond) of the naphthalene ring. The potassium to oxygen distances average 2.80 R and the oxygen-potassium-oxygen angles are close to 60, 120, and 180° as expected. The C-0 and C-C distances in the crown portion of the ligand average l.42 and l.48 3, while the C-O-C 34 Figure 6. The numbering schemes used for 2,3—naphtho-20-crown-6 complexed with KSCN (20), l,8-naphtho-Zl-crown-6 uncomplexed (g) and complexed with—kSCN (21). 35 and O-C-C angles average ll4.0° and l09.2°, respectively. Complete bond distances and angles for all non-hydrogen atoms are listed in Table l. The torsion angles for O-C-C-O and C-O-C-C average 64.4° and l75.8° respectively, in good agreement with previously published crown structures.35 The torsion angles for all non-hydrogen atoms are listed in Table 2. The naphthalene portion of the molecule is planar, with all ten carbon atoms within $0.004 4 of a plane which also contains the potassium ion. The naphthylic carbon atom (C6), which is bonded to naphthalene, lies 0.07 4 from this plane. The C-C distances in the aromatic ring average l.389 4 and the C-C-C angles 120.0°. The naphthalene plane is rotated Sl° about the twofold axis from the plane of the six oxygen atoms of the crown portion of the ligand. The results of the least-squares planes calculations are listed in Table 3. Figure 7 shows the molecule with the naphthalene plane parallel to the plane of the page. Figure 8 shows the molecule with the crown ether oxygen plane parallel to the plane of the page. There do not appear to be any strong intermolecular interactions observed in the packing of the complex in the crystal lattice. The disordered thiocyanate ion lies between two potassium ions, but the ends of the thiocyanate do not point towards the potassium ions. Figure 9 shows the packing diagram as viewed along (0 0 l). The model which was used for the disordered thiocyanate was the following: It uses a composite sulfur and nitrogen atom, and a carbon atom placed 36 Table l Interatomic distances (4) and angles (°) for 2,3-naphtho-20-crown-6 NS -c15 NS -c15a 07 -C6 07 -C8 0l0-C9 o1o-c11 013-c12 013-c14 c1 -c1a c1 -c2 c2 -c3 c3 -c3a c3 -C4 c4 -cs cs -csa cs -C6 C8 -C9 c11-c12 c14-c14a K -07 K -010 K -o13 1.054(8) 1. 652(9) 1.424(5) 1.411(4) 1.413(5) 1 A15(5) 1.412(5) 1 A20(5) 392(9) 1 .356(6) 1 .396(6) 1.419(7) 1.412(5) 1. 351(5) 1 A37(7) 1. 504(5) 1.479(6) 1 A93(7) ( 0 1.467 1 ) 2.733(3) 2.884(2) 2.796(3) NS -ClS-NS Cla-Cl c1 -c2 c2 -c3 c3a—c3 c3 -C4 C4 —c5 c4 -c5 csa-cs C5 -C6 C6 -07 07 -ca C8 -C9 -c2 -c3 -C3a -C4 -cs -csa -C6 -ce -07 -ca -C9 -010 C9 -010-C11 010-C11-C12 Cll-C12-013 012-013-C14 013-c14-c14a C2 -C3 07 - K 07 - 07 - 07 - 07 - 010- 010- 010- 013- 7<7<7<7<7<7<7<7< -c4 -07a -o1o -o1oa -013 -013a -o1oa -013 -o13a -013a 173.6(7) 115.4(4) 122.3(4) 118.1(5) 117.3(2) 124.4(3) 118. 3(4) 120. 0(4) 121. 6(2) 114.3(3) 115.4(4) 107.9(3) l09.9(3) ll3.5(4) 109.5(3) 108.8(4) 113.0(4) 109.7(4) 124.6(4) 66.31(5) 57.45(7 121.89(1 118.41(9 165.50(ll) 179.33(6 60.97(8 119.70(1 60.83(5) Symmetry code - (a) represents an atom at l-x, y, 3/2-2 37 Table 2 Torsion angles (°) for the potassium thiocyanate complex of 2,3-naphtho-20—crown-6 023-013- 01 -02 - 0.9 018-01 - 02 -03 1.0 01 -02 - 03 -03a - 1.0 01 -02 - 03 -04 -l80.0 02 -03 -03a -026 1.0 02 -03 -03a -043 l80.0 04 -03 -03a -04a - 1.0 02 -03 - 04 -05 179.9 033-03 - 04 -05 1.0 03 -04 - 05 -05a - 0.8 03 -04 - 05 -06 -177.1 04 -05 -05a -04a 0.7 04 -05 -05a -06a 176.9 06 -05 -05a -06a - 6.9 04 -05 - 06 -07 -129.3 053-05 - 06 -07 54.6 05 -C6 - 07 -08 90.2 06 -07 - C8 -09 172.4 07 -08 - 09 -010 - 56.0 08 -09 -010 -011 -l75.8 09 -010-c11 -012 -l73.6 010-011-012 -013 71.8 011-012-013 -014 179.8 012-013-014 -0146 -179.0 013-014-014a-013a - 66.4 Symmetry code - (a) represents an atom at l-x, y, 3/2-2 38 Table 3 Least squares planes for the potassium thiocyanate complex of 2,3-naphtho-20-crown-6 Plane l. The ten naphthalene carbon atoms -l2.367*x + 0.000*y + 7.0l7*z - 0.921 = 0.000 Plane 2. The six crown ether oxygen atoms -0.l87*x + 0.000*y + 7.809*z + 5.763 = 0.000 ------ Distance (4) ------ Atom_ to plane l togplane 2 K 0.000 0.000 Cl -0.004 C2 0.002 C3 -0.004 C4 0.003 C5 -0.002 C6 0.072 l.221 07 0.332 OlO -0.00l 013 -0.352 39 Figure 7. The potassium thiocyanate complex of 2,3-naphtho-20-crown-6 viewed with naphthalene in the plane of the page. Figure 8. The potassium thiocyanate complex of 2,3-naphtho-20-crown-6 viewed with the six crown ether oxygen atoms in the plane of the page. 41 Figure 9. Packing diagram for the potassium thiocyanate complex of 2,3— naphtho-ZO-crown-G viewed along (0 0 l). 42 at half occupancy about the twofold axis. The model used for the thiocyanate fits fairly well. The final difference map showed no residual electron density of any significance, indicating no incorrectly placed or missing atoms. The crystal structure determinations of l,8-naphtho-21-crown-6 (Q) and the potassium thiocyanate complex of l,8-naphtho-21-crown-6 (2_) were undertaken for much the same purposes as for 22, However, we were also interested in comparing the free ligand §_to its complex 22_and observing the conformational changes which took place. These 153.16 The numbering conformational changes have been noted elsewhere. scheme used for §_and 2§_is shown in Figure 6. The structure of §_shows a very rigid naphthalene system, while the crown ether hangs slightly to one side. There is no molecular symmetry present as there is in structures 22 and 22, The six crown ether oxygen atoms of §_1ie within :0.57 4 of a plane. These six oxygen atoms are not as planar as those in 22, owing to freedom from constraints placed on the molecule when it is complexed. The C-0 and C-C distances in the crown portion of §_average 1.421 4 and 1.506 4, respectively, while the C-O-C and 0-C-C angles average 112.35° and 109.55°, respectively. Complete bond distances and angles for all non-hydrogen atoms are listed in Table 4. The torsion angles for O-C-C- 0 average 74.95 for four of the dihedral angles. 010-Cll-ClZ-013 is, however, l79.l3°. This deviates significantly from the expected 60°, and indicates a significant conformational change from that of highly symmetrical 22_ The C-O-C-C torsion angles also show a deviation, with eight of the angles averaging l73.l3°, but with C6-07-C8-C9 and C8-C9- 010-Cll being 73.74° and 89.79°, respectively. The torsion angles for 43 Table 4 Interatomic distances (A) and angles (°) for l,8-naphtho-21-crown-6 01 -C2 1.427(7) C21 - 01 -C2 109.57(47) C2 -C3 1.517(7) 01 - C2 -C3 109.00(40) C3 -C4 1.419(7) C2 - C3 -04 108.05(42) 04 -C5 1.441(6) C3 - 04 -C5 112.05(44) C5 ~C6 1.503(8) 04 - C5 -C6 106.29(39) C6 -07 1.398(7) C5 - C6 -07 110.79(48) 07 -C8 1.420(8) C6 - 07 -C8 113.71(63 ) C8 -C9 1.530(10) 07 - C8 -C9 ll4.14(41) C9 -010 1.425(8) C8 - C9 -010 111.41(69) 010 -C11 1.416(7) C9 -010 -C11 114.66(48) C11 -C12 1.496(9) 010 -C11 -C12 105.87(4l) C12 -013 1.418(7) C11 -C12 -013 109.41(39) 013 -C14 1.426(7) C12 -013 -C14 112.00(45) C14 -C15 1.486(10) 013 -C14 -C15 109.66(39) C15 -016 1.420(7) C14 -C15 -016 109.85(58) 016 -C17 1.417(6) C15 -016 -C17 112.13(62 ) C17 -C18 1.509(8) 016 -C17 -C18 110.10(42 ) C18 -C19 1.428(8) C17 -C18 -C19 124.69(43) C19 -C20 1.451(7) C18 -C19 -C20 127.13(47) C20 -C21 1.498(7) C19 -C20 -C21 121.78(47) C21 -01 1.434(6) C20 -C21 -01 109.87(36 ) C20 -C2* 1.360(8) C20 -C19 -C10* 115.54(4 9) C2* -C3* 1.399(9) C21 -C20 -C2* 118.56(43) C3* -C4* 1.359(9) C20 -C2* -C3* 123.58(47) C4* -C10* 1.400(9) C2* -C3* -C4* 118.76(55) C10*-C19 1.446(8) C3* -C4* -C10* 120.83(58) C10*-C5* 1.420(9) C4* -C10*-C19 121.52(46) C5* -C6* 1.342(11) C5* -C10*-C19 119.50(58) C6* -C7* C7* -C18 Table 4 (cont'd) 1.396(11) 1.370(8) 44 C4* -C10*-C5* C10*-C19 C10*-C5* C5* C6* C7* C7* -C6* -C7* -C18 -C18 -C18 -C6* -C7* -C18 -C17 -C19 45 all non-hydrogen atoms are listed in Table 5. The naphthalene portion of the molecule is planar, with the largest deviation from planarity being C3* at 0.034 4. This is not quite as planar as the naphthalene portion of 22, but l,8-disubstituted naphthalenes are known to deviate from planarity. Table 6 shows a comparison of some different l,8-substituted naphthalenes. The naphthylic carbon atoms of §_are bent out of the plane by an average of 0.060 4. Overall, the naphthalene carbon atoms of §_(largest out of plane distortion is 0.034 4) are significantly twisted compared to dimethyl naphthalene (largest out of plane distortion is 0.012 4), but not as badly bent out of the plane as are those in 1,8- Qigfibromomethyl)naphthalene (largest out of plane distortion is 0.068 4). Table 7 shows the least squares planes for g, The angle between the two least-squares planes is 55°. The C-C distances in the aromatic ring average 1.397 4 and the C-C-C angles 120.04°. Figure 10 shows g_ with the naphthalene plane parallel to the plane of the paper. Figure 11 shows the molecule with the crown ether oxygen plane parallel to the plane of the paper. Figure 12 shows the packing diagram as viewed along (0 1 0). The structure of 22 is much like that of 22(they are both in the same space group), but 2§_is much less well behaved (see experimental). The R factor for 2§_is high, as is the goodness of fit. This should be kept in mind when evaluating the results of the structure determination of 22, Again, the twofold axis is a major structural feature. The potassium ion lies on this twofold rotation axis, and is 5.33 4 from C19, 4.87 4 from C20, and 6.08 4 from the center (midpoint of the C19- C10* bond) of the naphthalene ring. The thiocyanate ion also lies 46 Table 5 Torsion angles (°) for l,8-naphtho-21-crown-6 01 - C2 - C3 -04 - 86.0 01 -C21 -C20 -C19 175.2 01 -C21 -C20 -C2* - 5.8 C2 - 01 -C21 -C20 169.5 C2 - C3 - 04 -C5 -169.2 C3 - C2 - 01 -C21 176.2 C3 - 04 - C5 -C6 173.4 04 - C5 - C6 -07 - 69.3 C5 - C6 - 07 -C8 170.9 C6 - 07 - C8 -C9 - 73.7 07 - C8 - C9 -010 - 72.2 C8 - C9 -010 -C11 89.8 C9 -010 -C11 -C12 178.4 010-C11 -C12 -013 179.2 C11-C12 -013 -C14 174.1 C12-013 -C14 -C15 168.7 013-C14 -C15 -016 72.2 C14-C15 -016 -C17 -l71.9 C15-016 -C17 -C18 178.3 016-C17 -C18 -C19 - 79.9 016-C17 -C18 -C7* 100.0 C17-C18 -C19 -C20 1.4 C17-C18 -C19 -C10* -179.2 C17-C18 -C7* -C6* 178.8 C18-C19 -C20 -C21 1.6 C18-C19 -C20 -C2* -177.5 C18-C19 -C10*-C4* 178.2 C18-C19 -C10*-C5* 0.1 47 Table 5 (cont'd) C18-C7* -C6* -C5* C19-C18 -C7* -C6* C19-C20 -C2* -C3* C19-C10*-C4* -C3* C19-C10*-C5* -C6* C20-C19 -C18 -C7* C20-C19 -C10*-C4* C20-C19 -C10*-C5* 0.6 - 1.3 - 1.1 - 0.7 -l78.5 179.6 48 mm 0m om .wwm mnm.o 000.0 mm.— mmp.o m_oo.o .MHm mmm.o omo.o mm.— mmm.o Poo.o .Ham 00$ “cmsmu0pamwc mo 00:000m0e mu:_om0< 000.0 A0N0V0N0.0 0.0.0 Aem00000.0 0_.0 A_-00 00.0 000.0 A_-00000.0 000.0 A0-00000.0 0000000 mcmp0zu0a0: :00 0000000 mcmp00uca0: m0» PP0 mo ucmEmu0Famwc 00 0:0 00 000500000000 00000 mo “so ma0cm>< 0:0_0 $0 000 000mg00 .0000000 m:o_00u000: 00» >0 cowugoumwv o mp00h m .m 0000000000: -00000-0000-00000-0.0.0._ 000F000000: -A_0000000000Mmflm-0._ 000.000000e_0000000-0._ nanomeou mc0_0 00 “so 00 000050 000 0:0 .mm>wu0>wcmc m:m_000000c nmuauwum0nmiw.0 0500 we comwg0asou 49 Table 7 Least squares planes for l,8-naphtho-21-crown-6 Plane 1. The ten naphthalene carbon atoms 10.27l*x + 3.547*y - 3.639*z + 10.596 = 0.000 Plane 2. The six crown ether oxygen atoms -3.554*x + 4.409*y + 4.4l4*z + 1.884 = 0.000 O ------ Distance (A) ------ Atom to plane 1 to plane 2 C18 0.020 C19 -0.004 C20 -0.028 C2* 0.002 C3* 0.034 C4* -0.007 C5* -0.008 C6* 0.001 C7* 0.009 C10* 0.019 C17 0.056 0.452 C21 -0.064 -0.248 01 -0.342 04 0.057 07 0.405 010 -0.570 013 0.350 016 0.100 50 ' \ Figure 10. l,8-naphtho-21-crown-6 viewed with naphthalene in the plane of the page. 51 Figure 11. 1,8-naphtho-21-crown-6 viewed with the six crown ether oxygen atoms in the plane of the page. 52 Figure 12. Packing diagram of 1,8-naphtho-21-crown-6 viewed along (0 1 0 . 53 accross this axis, but it was found that the carbon of the thiocyanate refines best (or at least as well) when placed 93 the twofold axis. The naphtho-crown ligand is related, one half to the other, by this axis, with atoms C10* and C20 lying on the axis. The six crown ether oxygen atoms, all coordinated to the potassium ion, lie within :0.38 A of the best plane of the six oxygen atoms and the potassium ion, as well as the twofold rotation axis. The potassium to oxygen distances average 2.84 4 and the oxygen-potassium-oxygen angles are close to 60°, 120°, and 180° as expected. The C-0 and C-C distances in the crown portion of the ligand average 1.415 4 and 1.488 4, while the 0-0-0 and 0-0-0 angles average ll3.56° and 108.59°. Complete bond distances and angles for all non-hydrogen atoms are listed in Table 8. The torsion angles for O-C-C-O and C-O-C-C average 67.6° and l75.9° respectively. Once again, these values are in good agreement with published crown structures. The torsion angles for all non- hydrogen atoms are listed in Table 9. The naphthalene portion of the molecule is still moderately planar, with the largest deviation from planarity being 0.079 K (020). The potassium ion and twofold axis are also contained in this plane. The naphthylic carbon atom (C21), which is bonded directly to naphthalene, lie 0.379 4 from this plane. Again, this number should be put in perspective by the uncertainty in 22, The C-C distances in the aromatic ring average 1.386 4, and the C-C-C angles 120.39°. The naphthalene plane is rotated 39° about the twofold axis from the plane of the six oxygen atoms of the crown protion of the ligand. The results of the least-squares planes calculations are listed in Table 10. Figure 13 shows §_with the naphthalene plane parallel to the plane of the page. 54 Table 8 o Interatomic distances (A) and angles (°) for l,8-naphtho-21-crown-6 s -0 1.767(12) s - 0 -N l60.10(2.l9) N -0 0.913(27) s - 0 -sa 173.56(1.44) s -N 2.644(32) 021- 01 -02 ll4.68(84) s -N 0.955(23) 01 - 02 -03 107.57(67) 021-01 1.427(9) 02 - 03 -04 108.23(66) 01 -02 1.412(9) 03 - 04 -05 114.14(103) 02 -03 1.491(13) 04 - 05 -C6 109.88(87) 03 -04 1.410(10) 05 - 06 -07 108.13(77) 04 -05 1.418(13) C6 - 07 -C8 111.86(86) 05 -C6 1.475(16) o7 - 08 -08a 109.12(72) C6 -07 1.426(12) 020-019 -020a 126.74(52) 07 -C8 1.411(11) 019-020 -021 123.78(68) C8 -083 1.506(24) 020-021 -01 115.40(56) 019-020 1.429(10) 021-020 -02* 116.98(83) 020-021 1.511(12) 020-02* -03* 122.67(105) C20-C2* 1.365(12) 020-019 -010* 116.63(66) 02*-03* 1.400(15) 02*-03* -04* 119.67(137) C3*-C4* 1.317(17) C3*-C4* -010* 121.53(145) C4*-C10* 1.391(15) 04*-01o*-04*° 119.26(64) C19-010* 1.442(18) C4*-C10*-Cl9 120.37(74) K -01 2.824(6) 019-020 -02* 118.84(99) K -04 2.888(6) 01 - K -01a 67.04(12) K -07 2.813(6) 01 - K -04 57.86(l8) 01 - K -07 117.92(23) 04 - K -04° 178.41(15) 04 - K -07 60.11(20) 07 - K -07a 60.77(14) Symmetry code - (a) represents an atom at 1-x, y, 3/2-z 55 Table 9 Torsion angles (°) for the potassium thiocyanate complex of 1,8-naphtho-21-crown-6 019 -05*-04*-03* 1.7 019 -020-021-01 - 85.0 019 -020-02*-03* - 2.4 05* -019-020-021 -l66.8 05* -019-020-02* 5.8 05* -c4*-03*-02* 2.0 01 -02 -03 -04 64.9 01 -021-020-02* 102.3 04 -05 -06 -07 - 70.2 02 -01 -021-020 - 80.7 02 -03 -04 -05 175.6 03 -04 -05 -06 -178.6 03 -02 -01 -021 -171.1 05 -C6 -07 -C8 177.6 021 -020-02*-03* 170.6 020 -019-05*-04* - 5.6 020 -02*-03*-04* - 1.7 06 -07 -08°-08 177.4 021 -020-019-020a 13.2 020 -019-05*-04*a 174.4 020°-c19-05*-c4*a - 5.6 020°-019-05*-04* 174.4 020°-019-020-02* -174.2 04*°-05*-04*-03* -178.3 07 -C8 -C8 -07a 67.4 Symmetry code - (a) represents an atom at 1-x, y, 3/2-z 56 Table 10 Least squares planes for the potassium thiocyanate complex of l,8-naphtho-21-crown-6 Plane 1. Plane 2. The ten naphthalene carbon atoms -ll.3l9*x + 0.000*y + 7.235*z - 3.851 = 0.000 The six crown ether oxygen atoms -0.367*x + 0.000*y + 0.970*z + 1.754 = 0.000 ------ Distance (A) ------ Aggm_ to plane 1 to plane 2 K 0.000 0.000 C19 0.000 0.000 C5* 0.000 0.000 C4* 0.042 C3* 0.050 C2* -0.028 C20 -0.079 C21 -0.379 -l.218 01 -0.289 04 -0.026 07 0.377 C(SCN) 0.000 0.000 Figure 13. The potassium thiocyanate complex of l,8-naphtho-21-crown-6 viewed with naphthalene in the plane of the page. 58 Figure 14 shows the compound with the plane defined by the six crown ether oxygen atoms parallel to the plane of the page. The thiocyanate is again disordered, and lies between two potassium atoms. Figure 15 shows the packing diagram as viewed along (0 0 l). The model which was used for the disordered thiocyanate was the following: superimposed on The sulfur and nitrogen were placed at half occupancy, as was the carbon which is on the twofold axis. The model for the thiocyanate used in 22_ was tried, but did not fit as well. This model was the simplest to which we could adequately fit the data. It is possible that there is more disorder about the twofold axis, since some of the atoms have fairly large thermal parameters. The C-C distances in the crown ether portion of both 22_and 22 are fairly short. It has been observed that the C-C bond lengths in crown ethers are fairly short compared to the eXpected39 1.537 A or 1.523 3 measured for gas phase dioxane.40 Although several investigators have attributed the shorter than normal C-C bond lengths to inadequate treatment of thermal motion in refinement of positional parameters,41 2 Goldberg has Truter has concluded that the bond lengths may be real.4 done several studies on crowns at low temperature to reduce thermal motion effects. In addition, he has also used weighting schemes in the refinement of his data to attempt to correct for the thermal motion. In all instances, he continued to calculate the shorter bond lengths.43 Figure 14. The potassium thiocyanate complex of l,8-naphtho-21-crown—6 viewed with the six crown ether oxygen atoms in the plane of the page. 60 F1°9ure 15 Packin ' - 9 diagram for the otassi ' naphthO-Zl-crown-e vieweg alongumotgiocyanate complex of 1,8- 61 The C-C distances for 22 and 22_are about 0.02 A shorter than most crown structures, while §_is fairly normal. Apparently, the metal ion has a fair amount to do with determining the conformation of the crown ether in the crystalline state, as evidenced by the difference in symmetry between §_and 22, The crystal structure of 1,5-naphtho—22-crown-6 complexed with either cesium thiocyanate or potassium thiocyanate was not done, because suitable crystals of this complex could not be obtained. The conformational differences between the free and complexed ligand would be interesting, since the 1,5-naphtho-22-crown-6 has more severely restricted motion. 62 EXPERIMENTAL General. 2,3-Naphtho-20-crown-6 and l,8-naphtho-21-crown-6 were prepared as described earlier in this thesis. Both 22 and 22_were prepared by addition of equimolal amounts of potassium thiocyanate dissolved in a miniumum of methanol, and crown dissolved in several mL of ethyl acetate. This mixture was refluxed until all traces of solid were gone, and was then allowed to cool. The free ligand 6_was recrystallized from cyclohexane. The crystal dimensions are listed in Table 11. The space groups were determined by the diffraction conditions noted in Table 11. Diffraction data were measured with a Picker FACS-I automated diffractometer using zirconium filtered MoKa radiation. The cell parameters were determined by a least-squares fit of the angular settings of reflections in the range 35° :_20 5 40° and are shown in Table 11. The a] - 62 doublet was clearly resolved for 22 and 22, and was not recorded for 2_(A for MoKa = 0.70926 4). The unique reflections in the +h+ht£ region were calculated by e - 20 scans [1.0°(20) min-T] with three standard reflections measured after every 50 data to scale the data. The data were reduced and standard deviations calculated as a function of counting statistics.44 The least-squares refinement weights were calculated from the standard deviations of the structure factors by weight = l / (o2 + (0.02F)2). Extinction corrections were applied as noted in Table 12. Densities were confirmed by a pycnometer. 63 ¥ 000.0 00000.00_ 00000~.0 000000.00 000000.0_ N\mmm— Pmmm om omm 0» Uo c.0m o00 1 6mm op 0o .0\u zwnw "~00 :Nn0+: "0N0 ow.m 000.. 00000.0_0 000000.00 0_0000.0 000000.00 ~\m_0— mmwm om 6mm 00 go m.mm1m.mm GOG 1 0mm mp E\FNQ .Pma :mna "000 omm.o m0. x 0m. x NP. om. x mm. x mm. .mM 0 o 000., 00000.00, 000000.0 000000.00 000000.0_ F\momp scum op com 00 we 0.mm1m.m~ .00 - .00 00 00 .o\0 00.0 “000 00.0.0 .000 000.0 m. x mm. x _. MM 00.. 0 0 000005000010000 A0v000000\00>00000 000500 00000000000 000000 ~0000 A0000000 .000ov 00000000000 Aomv 00000 0000 00000000200 000000PP00 0000 A000000000 P_00V 00000 cm A000005000 p_00v 0000000P000 000000 00000 0_000000 0000000000 000000000_0 A_100V 0x02 000 0 AEEV 0000000200 —000z00 .0000000000 __00 000 .0000 000000__00 .0000 00000000000 pp mp00h 64 mp.o No.o wo.F mmo.o 00m.o mmp.o mm "20000020000 00 0 - 0000000_000 00 0V\A00 - omvzwg u .0.o.0 A thfiomvzw\mmA00 - ouvzwuv nmm 00 0\0_o0 - 00_00 u 0 _m.o m_.o A21000v 00000-00000 E0swx0s 00.0 00.0 A21000v 00000100000 0000000 00.0 00._ .0.0.0 000.0 _00.0 00 Fmp.o Fm_.o A0000 Fp0v a 000.0 000.0 m .0 .MM 0mm 000 «MM mm 00 0005000000 2000 00_0000 p0000 mp 0,000 65 Structure Solution and Refinement. The crystal structures were solved 45 Other programs used in this study included ORTEP,46 the with MULTAN. entire system of Allan Zalkin's programs,47 and programs written and / or modified locally. A CDC 6500 computer was used. The structures were refined to convergence by a full-matrix least- squares calculation. The final results are listed in Table l2. The average and maximum shift to error ratios are also listed in Table 12. Final difference maps showed no indication of incorrectly placed or 48 missing atoms. The scattering factors of Doyle and Turner were used for the non-hydrogen atoms, while those of Stewart, Davidson, and 49 were used for the hydrogen atoms. The anomalous scattering 50 Simpson factors of Cromer and Liberman were used for the non-hydrogen atoms, and anomalous scattering factors of zero were assumed for hydrogen. The atomic parameters for all three structures have either been published18 or will be shortly.17 Chapter 3 Crown Ether Modified Systems Designed to Probe Intramolecular Energy Transfer (Preliminary Studies) Introduction Energy transfer is generally thought of as a transfer of energy from an excited molecule to some other species; this energy can be in the form of vibrational, translational, or rotational energy. Hithout energy transfer, photosynthesis could not be nearly as efficient as it is, if it could even take place at all. Many biological systems are affected by energy transfer, and the effect which metal ions play in preturbing these systems is just beginning to be studied. The first observation of energy transfer was made by Cario and Frank in 1922 when they noted that a mixture of mercury and thallium vapor, when irradiated with light from the mercury resonance line, showed emfission spectra characteristic of both elements.51 Since the thallium atoms do not absorb the exciting light, they can get excited only indirectly by transfer of energy from the mercury atoms. This simple system laid the groundwork for work with more complex systems involving energy transfer. We are interested mainly in systems which deal with intramolecular energy transfer.52 The first complete study done on an intramolecular system was by 53 A mixture of 9-methylanthracene and l- Schnepp and Levy in 1962. methylnaphthalene, upon irradiation with light appropriately filtered to excite both the anthracene and the naphthalene, showed two fluorescence spectra, one characteristic of naphthalene, the other of anthracene. 66 67 When solutions of compounds 25, 22, and 22_were irradiated through this same filter, only anthracene fluorescence could be detected, indicating the presence of an energy transfer process. 23, n=l 22, n=2 22, n=3 Lamola et al.54 describe a system which uses ben20phenone and naphthalene as the chromophores in an intramolecular energy transfer study (compounds 22, 22, and 22). 21, n=l 22, n=2 22, n=3 Again, the absorption spectra of an equimolar mixture of 4- methylbenzophenone and l-methylnaphthalene had the same absorption as compounds 27_, _2_8_, and 2_9_. The only emission 01’ a sample 0f 4- methylbenzophenone and l-methylnaphthalene, irradiated at 366 nm, was phosphorescence of the 4-methylbenzophenone (366 nm selectively excites the benzophenone). This indicates little, if any, intermolecular energy transfer at the concentrations used. The phosphoresence of 22, 22, and 22_are nearly identical to that of l-methylnaphthalene, even when just the benzophenone chromophore (366 nm) is excited. This can be readily understood by looking at Figure l6. Light absorbed by the naphthalene 68 O .00 _ w“— 5' 5,—5. energy 8 0 — ’44" transfer __ T-T ener ”\— § 60 ' ' transgfgr T' GD CZ w 40 '— 20 _- O Figure 16. Energy levels of the first excited states of naphthalene and benz0phenone. 69 chromophore (3l3 nm) excites the naphthalene to its 1S state, which transfers energy to the 1S state of ben20phenone (singlet-singlet energy transfer, a process which in this case, the authors claim to be 90%, 75%, and 85% efficient for compounds 22, 22, and 22_respectively). Benzophenone readily intersystem crosses to the 1T state (oISC>O.99), which then transfers triplet energy to the naphthalene chromophore with l00% efficiency. This leads directly into our systems, compounds 22 and 21, Notice that compound 22_has an important modification to the system of Lamola 22_212, which adds the possibility of using a metal ion complexed by the crown to accept energy transfer from the donor to the acceptor. pm. 7 C) 70 31 A metal ion complexed to either 2_of 2_is known to preturb the emission and possibly the electronic structure of the naphthalene moiety.]2’14 Experimental evidence concerning the role of metal and non- metal cations on energy transfer is not available, despite the importance of energy transfer in living systems, where ions may play an important role. The eXpected conformational effect of a metal ion on crowns 22 and 21 from inSpection of CPK models is to flatten out the molecule through complexation, whereas the non-complexed crown may prefer a folded conformation. If compound 22_(or 21) transfers triplet energy from the ben20phenone to the naphthalene with almost total efficiency, this could be used to study the triplet behavior of naphthalene with almost all of the triplet state populated, and almost none of the singlet state p0pulated, something which can't be achieved directly for naphthalene. The effect of concentration of perturber may also be interesting. At high concentrations of crown compared to to preturber, large cation preturbers could complex with two crowns, and thus act as a template for intermolecular energy transfer. The effect 71 of a third chromophore held between benzophenone and naphthalene (held by attachment to a primary ammonium cation) would also be interesting. Results and Dicussion Synthesis of crowns 22 and 21 proved to be a non trivial task. The synthetic approach taken to these crowns was to attach "arms" (ethyleneoxy strands with a free hydroxyl) at one end, and then to form the crown by joining the ”two-armed" naphthalene to the 3,4- 21§(bromomethyl)ben20phenone moiety. Originally, the "two armed" naphthalene was to be made from displacement of the chloride in protected (tetrahydropyranyl ether) 2- (2'-chloroethoxy) ethanol by the alkoxide formed from the appropriate 212(hydroxymethyl)naphthalene and potassium thutoxide. In the case of 2,3-21§(hydroxymethyl)naphthalene (made from hydrolysis of the 912: acetate, which was in turn made from the dibromide), this gave poor yields (less than 2 %) of the two-armed material, some one-armed material, and mostly starting material. The reaction of l,8- 21§(hydroxymethyl)naphthalene with protected 2-(2'-chloroethyl) ethanol gave only poor yields of one-armed material, and gg_two-armed material. Presumably, this is due to the larger steric crowding in the l,8- disubstituted naphthalene system. An easier and better method involved formation of the sodium alkoxide of diethylene glycol with sodium, and then adding the appr0priate Qi§(bromomethyl)naphthalene in a small amount of THF and diethylene glycol to the refluxing slurry of the alkoxide. This method gives good yields of the two-armed naphthalene in both the 2,3- and 1,8- systems. 72 $3094.. @@ The small amount of one-armed material formed is separated by chromatography on silica gel, as is the naphtho-crown-B, which is the other undesired (!) side product (confirmed by spectral data). The other side of the molecule, 3,4-21§(bromomethyl)benzophenone (22), is formed by NBS bromination of 3,4-dimethylbenzophenone (23), which in turn is made by Friedel-Crafts acylation of grxylene with benzoyl chloride. 73 Although 3,4-2121bromomethyl)ben20phenone appears to be a solid, it can not be isolated as such from the reaction mixture. The reaction mixture from NBS bromination of 2g_is about 75% (]H NMR) pure 22, Attempted purification on alumina gives the solid cyclic ether 22_in poor yield. (3 .- The rest of the material appears to irreversably bind to the alumina, although more 22_does bleed off the column with time. This reaction of alumina with l,2-21§(halomethyl)arenes is known.55 A pure sample (greater than 95%) of 22 can be obtained by refluxing 22_in aqueous HBr, although 22_is still a waxy solid (mp is 42-46 °C). 22_was used 75% pure for the synthesis of 22_and 21, The crowns 22_and 21 were made as in chapter 1 from 22_and 22_(to give 22) and 22 and 22_(to give 21) in low yield. Figures l7-20 show emission specra of crown 22_(Figures l7, l8) and crown 21 (Figures 19, 20). Figures 2l and 22 show excitation spectra of 74 LOP >. — t: (D Z LIJ [.— E; LU 2 I.— <1 _1 LLJ I __ 0.0 1 ti 1 I I 400 450 500 550 600 WAVELENGTH (nm) Figure l7. Phosphorescence spectra of crown 2Q, Excitation is at 307 nm. Concentration is 1.0 x l0'4 M. INTENSITY RELATIVE 75 1 1 L J l J 400 450 500 550 600 650 WAVELENGTH (nm) Figure l8. PhOSphorescence spectra of crown 30. Excitation is at 350 nm. Concentration is l.0 x l0'4 FT.— 76 I.O [— >. t h— (D Z LIJ F r— E LL, _— 2 }_ <1 _ _J LIJ 0: 00 l l l I l 400 450 500 550 600 650 WAVELENGTH (nm) Figure l9. Phosphorescence spectra of crown 3l. Excitation iS at 307 nm. Concentration is l.0 x l0-4 W.- INTENSITY RELATIVE I.O 77 l l l l l 400 450 500 550 600 650 WAVELENGTH (nm) Figure 20. Phosphorescence spectra of crown 3l. Excitation is at 350 nm. Concentration is 1.0 x l0"4 W.- 78 I13-- )1. __ I: (I) 2:: +- LL] }_ Z _ LL] 2 *— #— <1 ._J 32' L o J l l 250 300 350 400 WAVELENGTH (nm) Figure 21. Excitation spectra of crown 21, observing at 4l5 nm. Concentration is 1.0 x 10'4 M. 79 |.0 - )_. I: (f) _. Z LIJ L_. Z LIJ 2 F" brihlrb>>P )E»Ein’P>>(>f>Pbrb> 4 a I m n a mwn . ..Ad.~ 1L [oh—e... 5E0 wan arv 00' 0PM w : Lr >1 51 .QN .DNM .52 l 6 6 N F '3 Q Ow“ @flm Owfi 00¢ 00— w.t b L r u r i» t b rib rib P b 1 L rhea» > P b that i >1» - Maw 09 Km 31 «SW. mam.— __ 1mm“ H. a. m _ . _w 6 flow ('1 h MNN u N u 00 r 90 Preparation of 3,3'-dimethy1benzophenone (22). To 3,3'- dimethylbenzhydrol (2.12 g, 10 mmol) in methylene chloride (20 mL) was added pyridinium chlorochromate60 (3.23 g, 15 mmol). The mixture turned black almost immediately. After 2 h, ether (20 mL) was added, and the solution filtered through a florisil plug. Solvent was removed under reduced pressure to give 2.05 g of g] (98%); 1H NMR (00013) a 2.20 (s, 6H), 6.9-7.1 (s, 8H); 130 NMR (CDC1 a 20.76, 123.19, 126.72, 127.36, 3) 127.58, 137.07, 143.79, 193.89; m/s.210- Preparation of 3',4'-dimethyldesoxybenzoin (22). To aluminum chloride (140 g, 1.05 mol) in 9:xy1ene (2 L) was slowly added phenylacetyl chloride (140 g, 120 mL, 0.90 mol) in a dropwise fashion at 0 °C. After addition, the reaction mixture was stirred for an additional 8 h at room temperature. The mixture was then washed with water, and the xylene layer was reduced under vacuum. The resulting oi1 crystallized on standing, and after recrystallization from methanol / water, gave 127 g (63%) of 22, mp 90-91 °c (lit - 95 °C)5‘; 1H NMR (00013) a 2.23 (s, 6H), 4.13 (s, 2H), 7.0-7.9 (br.m, 8H); 130 NMR (00013) a 19.43, 19.63, 45.05, 126.13, 126.42, 128.28, 129.16, 129.44, 129.53, 134.34, 134.71, 136.64, 142.33, 194.30; IR (neat) cm“ 1675 (s), 1610, 1595 (w); mfg 224. Preparation of 2e(3{,4'-dimethy1phenyl)-1-phenylethanol (22). To lithium aluminum hydride (7.6 g, 0.2 mol, x's) in THF (500 mL) was added 22_(22.4 g, 0.1 mol) in THF (100 mL) in a drOpwise fashion. The mixture was allowed to stir for 8 h, after which water (7.6 mL), 15% NaOH (7.6 mL), and water (22.8 mL) were added.24 After 2 h stirring, the pure white solid is filtered, and the filtrate evaporated under reduced pressure to give 22.5 g (100%) of a slightly yellow oil. An analytical 91 sample was prepared by molecular distillation (95 °C, 1 mm); 1H NMR (coc13) a 2.17 (s, 3H), 2.20 (s, 3H), 3.25 (d, 2H, J=7Hz), 4.88 (t, 1H, J=7Hz), 6.8-7.5 (br.m, 8H); 130 NMR (00013) a 19.06, 19.40, 45.58, 74.76, 123.08, 123.28, 126.00, 126.92, 127.97, 129.20, 135.23, 136.00, 138.19, 141.23; IR (neat) cm" 3100-3550 (br.,s), 1605, 1500 (s), 1450 (s); Eyg_226. Anal. Calcd. for C 0: C, 84.91; H, 8.02. Found: C, 84.75; 16H18 H, 7.94. Preparation of 3,4-dimethylsti1bene (21). To alcohol 22_(20 g, 88 mmol) in dry pyridine (40 mL) at 0 °C was SLOWLY added phosphorous oxychloride (20 mL, 220 mmol, x's). Solid appears in about 10 min, but the reaction is allowed to stir an additional 8 h. Ice was then cautiously added to the reaction mixture. When the original violence seceeds, water was added to a total volume of 40 mL. The solution is then extracted with ether (2 x 100 mL), the combined ether layers washed with cold HCl (4 x 25 mL), and the ether removed under reduced pressure to give a solid which was recrystallized from ethanol / water, 16.6 g (91%); mp 72-73; ‘H NMR (00013) 5 2.22 (s, 6H), 6.92 (s, 2H), 7.0-7.6 (br.m, 8H); 130 NMR (C0613) 6 19.37, 19.62, 123.91, 126.25, 127.16, 127.41, 127.68, 128.48, 128.64, 129.83, 134.89, 136.03, 136.53, 137.52; mfg 208. Preparation of 3,4-bis(bromomethy1)stilbene ( 2). NBS (3.5 g, 19.7 mmol) and fl1_(2.08 g, 10 mmol) in carbon tetrachloride (50 mL) were irradiated using a 200 watt sunlamp for 3 h. Although conversion to 32_ 1 is not complete, H NMR indicates that the reaction mixture is about 60 1 % pure 22, H NMR (CC14, external TMS) 6 4.42 (s, 4H), 6.88 (s, 2H), 7.0- 7.5(br.m, 8H). Chapter 4 Synthesis and Pr0perties of Ferrocene Crown Ethers Introduction The discovery of ferrocene (dicyclopentadienyliron) in 195162’63 has led to the development of a field of organometallic chemistry, that of the n-metallohydrocarbons. Numerous extensive reviews have appeared.64 The general method for the preparation of pentahapto- cyclopentadienyl compounds applies to ferrocene. 2 NaC H + FeCl2 = (h -C H Fe + 2 NaCl 5 5 5 5 5)2 A useful alternative method for the preparation of this "sandwich" or "Doppelkegel" compound i564’65 2 C5H6 + 2 (C2H5)2NH + FeCl2 = (h5-C5H5)2Fe + 2 (C2H5)2NH2C1 Ferrocene is an extremely interesting compound in that there is free rotation about the iron-cyclOpentadienyl bond(s). This allows us to construct a crown of variable size, which may conform to a variety of different cations. The name we have given to this is the "ratchet" effect. Most ferrocene derivatives, as well as ferrocene, can also be reversably oxidized to give ferrocenium ion, as is the case with the ferrocene crowns. 92 93 Results and Discussion Since 1,1'-21§(bromomethy1)ferrocene may not be a stable d’66 compoun it seemed that the only reasonable precursor for ferrocene crowns was 1,1'-21§(hydroxymethyl) ferrocene. To this end, we searched the literature for methods to make this known compound.67 Unfortunately, the majority of the literature methods were not reproducable, or gave yields drastically different from those reported by the authors. Raush and Ciapenelli68 report a synthesis of l,l'-ferrocene dicarboxylic acid which gives high yields (greater than 90%) from ferrocene. The method involves generating the 1,1'-di1ithio anion of ferrocene, followed by carboxylation with carbon dioxide. This dilithio anion failed to give 1,1'-21§(hydroxymethy1) ferrocene when treated with gaseous formaldehyde, or solid paraformaldehyde. This dianion gave polymer when treated with ethylene oxide in an attempt of make 1,1'- ferrocene diethanol. The method of Raush and Ciapenelli does form the ferrocene carbon-carbon bond in high yields. Direct reduction of 1,1'-ferrocene dicarboxylic acid proved to be futile, although this procedure has been reported.67 Attempts to reduce the diacid with diborane in THF,69 a reagent which is known for high yield reductions of diacids, failed to give 212(hydroxymethyl)ferrocene, as did direct reduction with lithium aluminum hydride. The dimethyl ester of 1,1'-ferrocene dicarboxylic acid reduces cleanly and in high yield with lithium aluminum hydride to give l,l'- 21§(hydroxymethyl)ferrocene. A method to get the ester from the acid in high yield was needed. Acidic methanolysis tore apart the ferrocene 94 structure. Methanolysis of the acid chloride, which was formed by thionyl chloride chlorination on the diacid gave poor yields, and involved a lengthy column.70 A much higher yield method involved methylation using a potent alkylating agent (dimethyl sulfate) with a weak comercially available base (2212(i50propanol)amine).7] The entire synthesis of 1,1'-21§(hydroxymethy1)ferrocene is outlined below. n. a... M1,... tr), .49". .AHP" liAIH TMEDA 4 . 21cc? ’ '7 (0131250, F. THF 43 ~ The synthesis is high yield, and has no tricky steps. The ferrocene crown ethers were formed by standard crown formation reactions, i.e. the reaction of a dialkoxide with the appr0priate polyethylene glycol ditosylate. The crown 5 and the crown 4 are shown below, with the crown 5 shown complexed to a cation. 95 The ferrocene crowns show a completely reversible oxidation in acetonitrile. Some preliminary eXperiments with alkali metal cations present during oxidation / reduction (cyclic voltammetry) shows little, if any, effect on the oxidation potential due to the presence of the alkali metal cations. This may be indicative of a very low complexation constant between ferrocene crown and cations.72 This could be due to either unfavorable iron-alkali metal interactions, or could be due to the fact that the ferrocene crown prefers the 180° anti-prismatic conformation.73 An interesting eXperiment which was not run, but should be, is to see if one can see the two ferrocenylic protons decoalesce into two separate peaks in the low temperature 1H NMR. These two protons are diastereotopic in all conformations but one. From this experiment, one could calculate the free energy of rotation about the cyclopentadienyl- iron-cyclopentadienyl bonds. 96 EXPERIMENTAL General. Hexane was refluxed over calcium hydride for at least 24 h, and then distilled from calcium hydride immediately before use. Microanalyses were performed by Spang, Ann Arbor, MI. Ferrocene was purchased from either Aldrich or PCR, Inc. The gel permeation column used to separate polymer from monomer used Enzacryl gel Kl, fine (Aldrich) which was swelled in THF for 24 h prior to column packing. All other instrumentation and procedures were as described in earlier portions of this dissertation. Preparation of 1,1'-ferrocene dicarboxylic acid (52). Prepared by the method of Rausch and Ciappenelli,68 yield 96%; mp dec over 245 °C 1 (1it.74 dec over 250 °c); H NMR (d onso) a 4.0 (br.S, 2H, CODH 6 exchanging with DMSO), 4.40 (s, 4H), 4.65 (s, 4H); 13C NMR (d -DMSO) 6 6 71.34, 72.66, 73.47, 171.13; 272.274- Preparation of 1,1'-bis(methoxycarbonyl)ferrocene (25). To l,l'- ferrocene dicarboxylic acid (15.0 g, 55 mmol) and 2212(isopr0panol)amine (22.0 g, 115 mol) in acetone (85 mL) was added dimethyl sulfate (13.89, 10.4 mL, 100 mmol) and the system refluxed for 3 h. The acetone was evapoarated, the resulting sludge taken up in benzene (200 mL), and washed with water (2 x 100 mL), 0.5 N hydrochloric acid (2 x 50 mL), then dried over magnesium sulfate, and concentrated under reduced pressure. The resulting solid was recrystallized from cyclohexane to give 14.5 g (87%) of crystalline 45; mp ll6-118 °c (lit 114-115 °0);67a ‘H NMR (00013) a 2.10 (s, 6H), 4.33 (t, 4H, 3=2 Hz), 4.75 (t, 4H, J=2 97 13 Hz); c NMR (c0c13) a 51.55, 71.49, 72.48, 72.81, 170.67; m/§_302. Preparation of 1,1'-bis(hydroxymethyl)ferrocene (32). T0 lithium aluminum hydride (1.68 g, 44 mmol, 2 fold x's) in THF (100 mL) was added 25 (6.7 g, 22 mmol). The mixture was allowed to stir for 12 h, after which water (1.7 mL), 15% NaOH (1.7 mL) and water (5.1 mL) were added. After an additional 2 h, the mixture was filtered, and the solvent removed under reduced pressure to give 5.37 g (100%) of 22, mp 96-97 °C; 1H NMR (c0013) 8 4.12 (s, 4H), 4.32 (s, 4H), 4.7 (br.S, 2H); 13c NMR (c0c1 a 60.15, 66.93, 67.90, 89.25; g/e_244. 3) Preparation of 1,1'-ferr0ceno-18-crown-5 (22). To potassium Erbutoxide (2.36, 21 mmol) in a mixture of THF (200 mL) and dimethylformamide (50 mL) was added with stirring a mixture of 1,1'- ngjhydroxymethyl)ferrocene (2.44 g, 10 mmol) and tetraethylene glycol ditosylate (5.02 g, 10 mmol) in THF (50 mL). Potassium tosylate (suspended shiny plates) was visible after 0.5 h, but the reaction was allowed to go 10 h. The mixture was then filtered through a diatomatious earth pad, and the filtrate concentrated under reduced pressure. The resulting yellow oil was chormatographed on alumina (400 9, Fisher neutral alumina), and eluted with dichloromethane to remove the first running fractions yellow and yellow-orange). A narrow fraction (orange) which started to move with 0.5% methanol in 1H NMR, the dichloromethane was collected, and although it gave a good mass spectrum showed higher molecular weight material was present. This fraction was then run through a gel permeation column with THF as solvent. 0f the two major bands, the second was found to contain 104 mg 22_(26%) as a brown, air and light sensitive oi1; 1H NMR (c0013) 6 3.67 98 13 (s, 8H), 3,70 (s, 8H), 4.0-4.2 (br.m, 8H), 4.30 (s, 4H); C NMR (CDC1 3) 6 67.97, 68.85, 69.01, 69.33, 69.54, 70.70, 71.10, 84.87; UV (95% ethanol) nm max 207 (€38,720); m/g_404. Anal. Calcd. for C20H2805Fe: C, 59.42; H, 6.98; Fe, 13.81. Found: C, 59.28; H, 6.90; Fe, 13.55. Preparation of 1,1'-ferroceno-15-crown-4 (22). Same as the preparation of 22, except that triethylene glycol ditosylate (4.59 g, 10 mmol) was used, 158 mg (4.4%); 1H NMR (00013) a 3.63 (s, 4H), 3.68 (s, 8H), 3.9- 4.2 (br.m, 8H), 4.37 (s, 4H); m/g_360. 23211_ Calcd. for C18H2404Fe: C, 60.01; H, 6.72; Fe, 15.50. Found: C, 59.93; H, 6.79; Fe, 15.29. Preparation of 1,1'-ferroceno-21-crown-6 (fl_). Same as the preparation of 52, except that pentaethylene glycol ditosylate (5.47 g, 10 mmol) was used. The compound decomposed prior to final purification on gel permeation column; 1H NMR (CDC13) 6 3.6 (br.S, 20H), 4.1 (br.s, 8H), 4.3 (br.S, 4H); 072.444- Chapter 5 A Working Minicomputer - Fluorescence Spectrophotometer Interface Introduction During a recent study on excited state processes of naphthalene 125’13’14 it became necessary to devise a better crown ether derivatives, way to handle the calculation of fluorescence and phosphorescence quantum yields. Although this only involves comparison of integrated areas, the areas must be expressed in units of cm'1 instead of nm, and there is no simple relationship between the areas defined by the two inverse quantities nm and cm']. To directly obtain Spectra which were a function of cm"1 would require unreasonably extensive hardware modifications to the fluorescence Spectr0ph0tometer. The first method used to solve this problem involved tedious digitization of fluorescence and phosphorescence Spectra (sometimes taking up to three months for a set of fifty spectra), running these data points through programs designed to integrate over the spectral regions involved, and comparing the resulting regions to a standard. These progrms are described in more detail in the next section, and are listed in Appendix B. The decision to interface the Hitachi / Perkin-Elmer fluorescence SpectrOphotometer to a digital computer was made when it became clear that not only was a backlog of potentially useful data accumulating, but also that an interactive system would facilitate periodic running of standards to check for machine drift. The project entailed design of an analog-to-digital converter (A/D) interface to a PDP8/E,75 followed by development of software to drive the interface and interact with the 99 100 Hitachi / Perkin Elmer. Due to a necessitated Operating system change on the PDP8/E, a new software System was written which also gave expanded capabilities. Both of these programs, the first written in BASIC and the second in a mixture of FORTRAN 2 and SABR, are listed in Appendix A. Results and Discussion The original system of data collection which depended on digitalization of Spectra followed one of three paths, depending on the Spectrofluorometer which was used for data collection (see Figuire 25). The main data processing program was COREK (data COREction and reduCtion program). Data could be submitted directly (by cards) into COREK, but the input to COREK was moderately tedious and complicated, and the personel using the programs were moderately unskilled in the use of digital computers. Computer turnaround at this particular time was Slow, and an error in the input deck for COREK would usually mean a one day delay in productivity. Also, the typing of repetitive title cards for each spectrum was tedius. Therefore, an interactive system of programs was devised to submit a "gramatically" correct input deck for COREK. TICARD (TItle CARD program) would use as input digitized data punched on cards, and stored on a disk file in the CDC 6500 system. After placing appropriate title cards in the data deck, TICARD would create a file which would serve as input for CIP (Corek Interactive Program). TICARD also checked data for errors in format. CIP would interactively create a deck for submission to COREK. Program COREK read in standard Spectra to correct background in the experimental spectra, 1 and after subtracting this background, would convert nm to cm' and 101 Data Collection Digitization of Data 1 12 3 Program TICARD 1 Program 1’ CIP Program INTEG ¢.Program COREK l. Aminco - Bowman with computing experience. 2. Aminco-- Bowman. 3. Perkin - Elmer. Figure 25. System for data reduction prior to the computer interface. 102 integrate. The spectra would then be plotted on the line printer, and if desired, a "good" CALCOMP plot of these spectra could be obtained. The quantum yield was also calculated. After using this system for several months, a new fluorescence spectrophotometer, the Hitachi / Perkin-Elmer was obtained. The decision was made that all of the plots were not really very useful, and Since the Hitachi corrected each Spectrum, a program just to convert nm to cm'], integrate, and calculate quantum yields was all that was needed. Program INTEG (INTEGration program) did just this, and was moderately short. The laborious part of this whole system was still the digitalization of spectra. In addition to the immediate acquisition of areas and quantum yields, a method to check the Hitachi / Perkin-Elmer for reliability was needed, since the instrument would occasionally drift. A fact which was discovered after the interface was up and working was that visual inspection of spectra could not determine subtle differences which could account for as much as a 10% error in area. An A/D interface was designed by Mr. Martin Rabb and Dr. Thomas Atkinson. The card which contained the interface for the A/D converter and the PDP8/E also contained a programmable read only memory (PROM) which was wired for field 7 (the highest field of memory) of the PDP8/E. A program to boot several system devices (including SLSi floppy disk 76 drives) as well as load either the RIM loader or the Absoulte Binary 7 78 and placed in the PROM.79 The A/0 interface "35 Loader was written software compatible with the Digital Equipment Corporation (DEC) A/D package. Originally, we had not intended to use the 2 V corrected Signal which comes from the computer in the corrected spectra accessory 103 (it serves no other function! - it may have been intended for just such an application). Instead, we had planned on using the 10 mV input to the strip chart recorder. Insurmountable problems were encountered in attempting to amplify this Signal adequately. A pulse from the CPU of the PDP8/E was inherent in the circuitry, and interfered with true A/D sampling, showing up as "random" noise. Thus, the 2 V Signal was used to record data. This really made more sense, Since it seems redundant to cut a 2 V Signal to 10 mV for a strip recorder, only to try to amplify it back to a reasonable level. The method of synchronization between the mechanical movement of the Hitachi and the real time programable clock80 in the PDP8/E was the next decision to be made. Ideally, the computer would use a digital-to- analog converter to actuate a response from the Hitachi. The expense and other factorsg] led us to use another method. When the switch which acutates the wavelength advance is closed on the Hitachi, a relay is flipped which starts the chart recorder motor. This recorder output was monitored by a second A/D channel, and when a voltage change was encountered, the computer was freed from a static loop into the actual data collection part of the program. Since the chart recorder and Hitachi wavelength drive had to be well synchronized, the Hitachi and the clock in the PDP8/E were also well synchronized. One additional feature of hardware (and indirectly software) Should be discussed prior to the interface programs. The floppy disks on the computer were extremely unreliable over long periods of time. Although the data collection programs had a restart option included in them, this problem was often more than a minor annoyance. If the floppys had a failure during the running of a program written in BASIC, the system had 104 to be re-booted, a process which required manually keying in eighteen instructions. The reason for this was that the 08/8 monitor had been swapped out by BASIC, unlike the FORTRAN system which leaves 05/8 in the last page of the first 8 K of core, with location 76008 (or 76058) available for re-entry into 05/8. Although switching to the FORTRAN system aided in error recovery, the major aid to solving this problem was completion of the PROM bootstrap which resided in locations 770008 to 77777 The OS/8 handler for the SLSi floppies was also modified to 8' decrease System failures. During diagnostics, it was noted that often when an error occured, it could recover through a re-try, averaging about 5 re-tries when this error occured. Since the old handler only allowed 3 re-tries, that number was changed to 2008. This fixed a large percentage of the problems. One additional source of problems was the highly “patched" nature of our version of 05/8 version 3C. The BASIC compiler in this version had some severe problems which were "fixed" by patches. However, these patches often led to seemingly random (though often reproducible) errors. When 0S/8 version 30 was released, BASIC was much improved, but the library of routines which contained A/D software no longer worked, due to some of BASIC'S internal subroutine numbers not being updated in the patch. Since DEC was giving minimul support, the data collection program was rewritten in FORTRAN 2. This software / hardware package seemed to Operate with minimal downtime. As previously mentioned, the first data collection program was written in BASIC. After a certain amount of initialization, the program would request whether or not the current set of runs was a restart.‘ This allowed either a fresh start, or for old areas from previous runs to be read in and stored, with the run counter starting at the next 105 available run number. One could also change the run number to re-run certain Spectra (such as standards). The starting and ending wavelength were then input, as well as the Speed at which the data were to be collected. Only three Speeds of the Hitachi were truely useful for quantum yield determinations, those being 240, 120, and 60 nm per minute. The number of data points which could be sampled in a second, given BASIC'S huge overhead, was about 250. Thus, 240 data points per second was determined to be a "safe" number to collect. Original attempts to use only one A/D conversion to give a data point diSplayed the considerable noise still inherent on the data line between the Hitachi and the A/D circuitry. By taking many A/D conversions for each data point and averaging, a very reproduceable digital representation of the spectra being taken was obtained. Sampling was done at 240 points per second, and data were stored at 1/2 nanometer increments, so when runing at 120 nm/min, we collected and averaged 60 data points every 1/4 second, then stored this point. For 60 and 240 nm/min, we averaged 120 and 30 data points respectively. Data were collected as soon as the computer was released from a 100p by a change in voltage at the recorder relay which was being monitered by the second A/D channel. Within the actual collection routine, the correct number of data points would be sampled, averaged, stored, and then the computer would wait for an overflow from the clock. If an overflow occured before the sampling and averaging was done, a message to note a timing error was printed. After collection of points, the spectrum had to be integrated. After determining the lowest point in the spectrum, and refering to this point in nm, the program would allow placement of a baseline (which could be sloped). The program also allowed the user to decide where to 106 start and st0p the integration in nm. After integration, this procedure could be repeated if the results were unsatisfactory. Otherwise, the program allowed one to calculate the quantum yields by dividing the integrated areas from individual runs by areas determined for standard compounds and multiplying by the known quantum yield for the standard. A correction for different sensitivity settings and different efficiencies of absorption relative to the standard could be applied. The program then cycled to input the next Spectrum. There were some disadvantages to the data collection program in BASIC. The first was the extensive use of disk that BASIC must make. In fact, it was necessary to put an unnecessary call to the A/D converter in the program so that BASIC would swap out string-handling routines and swap in the routines for A/D conversions. This could not happen in the data collection loop, as it would obviously interfere with the rather delicate timing required for sampling. Another disadvantage was that once sampling started, there was no way to restart the run other than killing the program. This restart was often a necessity if something was not properly set on the Hitachi. A previously mentioned disadvantage was the inability to boot 05/8 directly when BASIC failed. The second data collection program was written in a combination of FORTRAN 2 and SABR. SABR code is essentially assembly language, and has the advantage of being able to be mixed directly with FORTRAN 2 code. This second program is essentially a direct translation of the first, except that it is much more modular. It also solves the problem of interrupting the data collection routine. Subroutine AHEM checks to see if a character has been entered from the keyboard. If it has, data collection is irrecoverably terminated, 107 and the run is restarted. Subroutine CLW waits for the clock to overflow. It does not generate an error if the timing is off, but this feature is not really needed. A conservative estimate of the maximum collection rate in this program is 1000 points per second, much faster than with the Slower BASIC. This tended to give us "truer" data points after averaging, but the effect on the areas was not perceptible. Subroutine CLK which starts the real time clock should be changed if rates of higher than 240 nm / min are to be used. The use of disk was minimized in this program, and was used only as a back-up. The computer to fluorescence spectr0photometer interface allowed virtually instantaneous integration of Spectra, with integration taking place in less than five seconds. A typical days run could handle fifty to one hundred spectra, which would have taken several weeks intensive work in the past. Two other computer programs which are listed in Appendix B are UCHECK and ATOMOV. These programs are intended for usage with a computer program written by Professor J.F. Harrison to perform INDO 82 ‘6 UCHECK is used to calculations and have been extensively used. check input parameters, and calculate distances within a given cutoff from cartesian coordinates. ATOMOV will generate a vector between two atoms, move one of the two atoms along this vector to a new bond length, and output the cartesian coordinates. 108 EXPERIMENTAL General. A Digital Equiptment Corporation PDP8/E minicomputer with 16 K words Of memory, a programmable real time clock, and dual Standard Logic Systems floppy disks was interfaced tO a Hitachi / Perkin-Elmer Spectrophotofluorometer Model MPF-44A with a computerized corrected spectra accessory. A 2 V corrected signal from the corrected Spectrum accessory was converted to a digital value by the A/D converter in the PDP8/E, and the digital value acquired by software. All other computer programs were performed by the MSU-CDC 6500 computer running under the HUSTLER Operating system. Chapter 6 Some Studies Directed Toward the Synthesis Of (+)-Disparlure Introduction The gypsy moth is a serious defoliator of forest, Shade, and orchard trees in the northeastern United States, and is rapidly Spreading to the South and more slowly to the West.83 When DDT (6,6- 912(p7chlorophenyl)-B.B.B-trichloroethane) became available in the late 1940's, it served as an effective weapon against the gypsy moth. However, DDT'S use was curtailed in 1958, and has been illegal through most of the 1970's.84 In 1970, the gypsy moth defoliated 800,000 acres of forest, and in 1971 this figure rose to 1.9 million acres. The two methods currently in use to attempt to stOp the proliferation of the gypsy moth are the following: 1) The importing Of parasites and predators which can control the gypsy moth through natural biological processes. 2) Carbaryl (Sevin), an insectiside which is effective against the gypsy moth, but is applied at the rate Of one pound per acre. Other methods including the use of a fatal larval virus have been attempted, but all have had little success in achieving anything but partial control. The gypsy moth population has certainly not been decreased.83 In 1970, the structure Of disparlure, the sex attractant produced by the female gypsy moth (Lymantria dispar or Porthetria dispar (L.)), 85 was Shown to be 912:7,8-epoxy-2-methyloctadecane. With this discovery, coupled with the ability to synthesize disparlure, one could fight a 109 110 more modern battle with the gypsy moth, using its sex pheremone to disrupt and confuse its mating habits. The first synthesis of racemic disparlure by Beroza and coworkers85 involved the epoxidation Of the Olefin (2)-2-methyl-7-Octadecene, which was in turn prepared by a Wittig synthesis from 6-methylhepty1 bromide and undecanal. A very similar synthesis Of Bestmann and Vostrowsky86 used the alcohol formed from isoamyl magnesium bromide and oxetane, followed by hydrogen bromide treatment to give 6-methy1heptyl bromide. The synthesis was identical to that Of Beroza and coworkers after that point. Several other racemic syntheses have appeared in the literature, but one Of the most novel is the work of Kluenenberg and Schaefer,87 which involves a double KOlbe electrolysis. O _+ _._. __._. 02H C0211 02H CO2MO , CO / \ m Clch‘ “a (iI-dlsporlure 01310-1219 (c112) 4cwicw312 The starting material (2,2)-l,5-cyclooctadiene is the source of the (2)- alkene which is epoxidized to disparlure. The KOlbe electrolysis is used to place the two alkyl groups on each side of the (2)-alkene. Although these syntheses afford racemic disparlure in good yield, the racemic mixture is not nearly as attractive to the male moths as the (+) 88 enantiomer, making the need for a stereOSpecific synthesis acute. The first stereOSpecific synthesis Of (+)-dispar1ure89 90 by Marumo and coworkers established the configuration Of the active enantiomer Of disparlure through synthesis of both enantiomers and concurrent activity testing Of each Of these two enantiomers.91 111 Ts 0 H01. 150’ («Q-disparlure (—)~disporlure The chiral center in (S)-(+)-glutamic acid gives rise to the C-7 center in the final product; the transformation is achieved directly for the (-) enantiomer, and with inversion through SN2 displacement in the (+) enantiomer. The configuration of the C-8 center is asymmetrically induced. If a tosylate group is attached to C-8, then the center is formed by inversion (-). If a hydroxyl group is attached to C-8, then the configuration is retained during epoxide formation (+). Although the synthesis is elegant, it is fairly long, and would not be adaptable to a larger scale. One fairly intersting entomological result which surfaced from this investigation is that the receptor system in the Olfactory organ Of the male insects is chiral, reSponding to the (+)- disparlure preferentially to the (-) enantiomer and the racemate. A severe limitation of the synthesis is that the products are contaminated with at least 5.8% of their enantiomers. 112 Mori reports a Synthesis Of (+)-disparlure which is better than 98% enantiomerically pure, and provides sufficient quantities of material (more than 1 gram) for wind tunnel bioassays, electro antennagrams, and field testing.92 The source of Optical activity for Mori's synthesis was (25:3S)-threo tartaric acid (L-(+)-). c0211 These asymmetric carbons give rise to C-7 and C-8 in disparlure directly. Although the authors point out that the crystalline nature Of the immediate precursor to disparlure allows for repeated recrystallization, and therefore high enantiomeric purity, it should be noted that the precursor possesses only two assymetric carbon atoms. The precursor has availiable only two diastereomers, and both would give rise to a 1222§_analog of disparlure. Unless the already highly enriched pro-(+)-gi§_enantiomer would preferentially recrystallize, the authors only have a method to assure high purity, not high enantiomeric purity. 1H NMR tests of one Of the aforementioned precursors gave estimates Of greater than 98% purity. Although this synthesis gives high enantiomeric purity, it still suffers from its length. An additional shortcoming Of this synthesis is the possibility for racemization in the last step. Recently, Pirkle and Rinaldi93a report a synthesis which generates a non-resolved mixture Of enantiomers which are virtually identical to 94 t the hydroxysulfide intermediates generated by Farnum et al.. he 113 difference being that in the Farnum synthesis, the hydroxysulfide has been prepared Optically active. Pirkle resolves his intermediate by separation Of diastereomers generated from the reaction Of hydroxysulfide and (R)-l-(1-naphthyl) isocyanate. This step although acomplishing its goal, requires a very expensive chiral reagent, rendering this synthesis useless for large quantities of disparlure. It d93b for procuring very pure (+) and (-) may however provide a metho disparlure samples, by applying the method two or three times to the hydroxysulfide intermediate of Farnum 21_21, Currently, the method of Farnum 21_211_is the only source for large quantities of disparlure. The modified and scaled-Up version has been used to provide a 35 9 quantity to the U.S.D.A. for field testing (1978), and with some furthur improvements, Should be able to yield kilogram quantities on an industrial scale, perhaps as cheaply as $200 per gram. The synthesis Of Farnum 21_211_is outlined in Figure 26. Notice that the enantiomerically pure source does not contain an asymmetric carbon which ends up in the final product as do the syntheses of Marumo and Mori. Instead, the (£)-menthol is used to fix the stereochemistry Of sulfur in the sulfinic ester, which in turn asymmetrically induces the configuration of the a-carbon atom formed by the subsequent aldol. After condensation with undecanal, one is again left with two diastereomers which must be separated. The sulfur (now in the form of a sulfoxide) is reduced, and therefore loses its asymmetry, although C-7 and C-8 in the pro-cis sulfide have already had their stereochemistry fixed in the preceding aldol-like condensation. 114 H \u ’70- "Cl“ H 525 ~ + ‘ - H H111! "diocuzc'fioc "2 H 1111 1K)! THF 5"" 53 ~ ”(CI-13);, 0054 ”NOW/CH2C12 H”, ow m a: (*1 “dispoflon Figure 26. Modified synthesis of Farnum et a1. 115 Results and Discussion As previously mentioned, the method Of Farnum has been scaled up to provide 35 g Of (+)-disparlure. Several problems which this author worked on were the following: 1) A cheap source for 6-methylheptyl bromide (§_), previousy purchased from Chemical Samples Company. 2) Scale up Of the two hydroxysulfoxide forming reactions (from the tolyl sulfoxide), and some work on the relative yields of pro-cis (52a) and pro-trans (52b) hydroxysulfoxide. 3) Scale up of the reduction of the pro-£12_hydroxysulfoxide (222) to the pro-£1§_hydroxy sulfide (22). 4) Scale up Of the epoxide (disparlure, 23) formation from the pro- £12_hydroxysulfide (22). 6-Methylheptyl bromide, although a seemingly Simple molecule, turned out to be moderately difficult to Obtain cheaply in large quantities. One procedure which failed was the cleavage of 6-methyl-1- d95 with aqueous hydrogen heptanOl-O,O,O-triester Of phosphorthioicaci bromide to give the alkyl bromide directly. Reductive cleavage of this triester with lithium aluminum hydride also failed to give 6- methylheptanol. Direct Grignard displacement on an alkyl bromide also did not work. However, the Grignard coupling reaction can be made to work by the addition of Cu”,96 presumably involving the intermediacy Of a lithium dialkyl cuprate.97a lags, [ */1\\//1\\ J .“\\/’“\c/"' ‘+ '-'-'.> LNZu I2 *i’ >>__\\'//\\'/’\\1k LiCuCl‘ Apparently the displacement Of bromide is a more facile process than 116 Opening the tetrahydrofuran (solvent) ring, a known process for the lithium dialkyl cuprates. This method, which involves the adition Of isoamyl magnesium bromide to l,3-dibromopropane with a catalytic amount Of lithium tetrachlorocuprate, is capable of generating large amounts of 6- methylheptyl bromide; a very careful distillation is required, however, to separate the desired product from l,3-dibromOpropane and unreacted isoamyl bromide. The scale up Of the two step reaction sequence which converts the tolyl sulfoxide (22) to hydroxysulfoxide (22) was plagued by a variety Of problems. The first step, which involves displacement Of a tolyl group by a Egggfbutyl anion, was moderately easy to scale up. The only significant change was to transfer the 1221fbutyl lithium by canula rather than syringe. However, the second step caused two major problems. The first problem was formation Of excessive amounts of "pre- cis".98 This material was identified as 5-pentadecanol on the basis Of spectral data. The amount Of "pre-giéf could be restricted by allowing longer periods for anion formation (up to one hour instead Of several minutes as previously done) and the drOpwise addition Of undecanal to minimize the Side reaction Of addition of n-butyl lithium to undecanal. The second major problem was never successfully overcome. The pro-£1§_ to pro-1222§_hydroxysulfoxide ratio was reported to be 45 to 30 by Farnum 21_21, This ratio promptly reversed itself during the 35 gram production sequence. The only success towards increasing the amount of pro-g12_was to change the aqueous ammonium chloride quench for the reaction from 0°C to -78°C. The reasoning behind this was the following: Although the original aldOl-like condensation may have been 117 completed with a ratio of 45/35 pro-cis to pro-trans, during the warming before the quench, a retrograde aldol may have occurred. If this retro- aldol were followed by an aldol which did not give the same kinetic and / or thermodynamic control as at -78°C, the respective yields would be changed. In this regard, we were partially successful by changing the pro-£1§_to pro-1222§_ratio to 35/45. Although we seem tO have increased the overall yield of aldol product, we have not decreased the amount Of pro-1222§_formed. Future research into this reaction should include the effect Of metal ions on this condensation, in particular the effect Of an additional equivalent of either lithium or tetramethylammonium salts as both are known to affect the stereochemistry of the aldol 98 The results must be carefully checked Since salt condensation. addition may change the stereoselectivity of the lithium sulfoxenolate formation, and therefore contaminate the product with (-)-disparlure. Reduction Of the hydroxy sulfoxide (22) to the hydroxysulfide (22) b stannous chloride proved tO be very difficult to scale up. In addition, the two-step sequence to accomplish the reduction Of a sulfoxide to a sulfide seemed tedious. A new method using sodium )99 was employed. Initial 100 212(methoxyethoxy) aluminum hydride (Vite experiments using the procedure of Ho and Wong gave not Only the desired hydroxy sulfide, but also a vinyl sulfide. Apparently, addition at room temperature induces some elimination. A change Of solvent from benzene to tetrahydrofuran, lowering Of the temperature during addition to -78°C, and subsequent warming to 65°C gave the desired sulfide in 81% yield, only a 5% decrease from the previous two step method. A small test run in tetrahydrofuran with addition Of Vite at room temperature gave eliminated product. Another test run in which Vite was added at 118 -78°C in tetrahydrofuran, warmed to 25°C, and allowed to stir overnight gave no reduced product. It seems necessary that addition Of Vite be done at low temperature, and that in tetrahydrofuran the reagent be warmed to effect reduction. One reagent which should be explored in the future for this reaction is sodium cyanoborohydride with a catalytic amount Of crown ether added. Durst et al.10] use this reagent tO reduce alkoxysulfonium salts formed from the reaction of a sulfoxide with methyl flurosulfonate or trimethyloxonium tetrafluoroborate. Their yields were aS high as 91% for the two step overall process of reduction from sulfoxide to sulfide. The last problem undertaken in this synthesis was the scale up of the final epoxidation sequence. The method Of choice still remains methylation using trimethyloxonium tetrafluoroborate in nitromethane / methylene chloride, and subsequent epoxide formation using aqueous sodium hydroxide in a two phase system. There are two major problems with this system. One problem is that it is inconvenient to remove the nitromethane / methylene chloride solvent mixture very rapidly, making scale up a tedious procedure. It is necessary, though, Since nitromethane would become an excellent nucleophile in the presence of base. The other major problem is that the reaction will occasionally fail and/or give poor yields. This author has not been able to determine the reason for this. Attempts to change the reaction conditions met with failure. The simplest change seemed to be to use methylene chloride alone in the methylation step. There are several examples in the literature for 93,102,103 this. This methylation seemed to be sluggish, but appeared to work satisfactorily on a 5 gram scale. A scale Up to 25 gram failed, 119 with the yield Of disparlure about 20%. The basic problem seems to be insolubility Of trimethyloxonium tetrafluoroborate in methylene chloride. A change in methylating agent to methyl fluorosulfate (a @222. cheaper reagent than trimethyloxonium tetrafluoroborate) might solve this problem as well as reducing the time for methylation to under 5 minutes.104 Several other methylating agents have been tried on this system by previous workers including methyl iodide and dimethylsulfate. None Of these reagents gave acceptable results. Another possibility is to use a co-solvent with methylene chloride which is not nucleOphillic in the presence Of sodium hydroxide. An excellent choice might be iSOprOpanol. A 25 milligram reaction run with a 1:1 mix Of isoprOpanOl and methylene chloride with 1.1 equivalents Of trimethyloxonium tetrafluoroborate for 30 minutes, followed by 0.5 N sodium hydroxide treatment gave disparlure (t.l.c.), but no quantification of this reaction was done. The overall synthesis as it now stands is still the only commercially viable synthesis. With improvements, this synthesis could provide kilograms Of (+)-disparlure per year for testing and control Of the gypsy moth. 120 EXPERIMENTAL General. Gas chromatograms were determined on a F 8 M Model 700 Laboratory Chromatograph using a 10 foot 30% SE-3O on Chromosorb W column at 170°C. Purities of products were determined by thin layer chromatography (t.l.c.); identification Of known compounds was accomplished by t.1.c. or g.c. Final purity of (+)-disparlure was evaluated by gas chromatography on a 50 foot 3% OV-l on Gaschrom Q microcapillary column in a Packard gas chromatograph in Dr. Ring Carde's lab at M.S.U. All other instrumentation and procedures were as described in earlier portions of this thesis. The following experimental is a bit more detailed than usual tO aid those running these reactions with little previous experience. Full spectral data will be published at a later date.105 Preparation Of 6-methylhepty1 bromide (22). TO a flame dried 3L three necked round bottom flask, equipped with a mechanical stirrer, condenser with nitrogen outlet, and a condenser with a 1 L addition funnel and nitrogen inlet, were added pentane washed magnesium turnings(l46 g, 6.0 mol) and l L dry THF. A crystal Of iodine was added to the flask, and the drOpwise addition Of isoamyl bromide (453 g, 3.0 mol) is 500 mL THF was started. The solution was vigorously refluxing in about 5 min. The isoamyl bromide was added over a period of 2 h, and the solution in the flask then refluxed (with additional heating) for another two h TO a flame dried 5 L three necked round bottom flask immersed in an ice bath, 121 equipped with a mechanical stirrer, thermometer, and l L addition funnel was added l,3-dibrom0propane (606 g, 3.0 mol) and 30 mL Of a 0.1 m solution Of lithium tetrachlorOCUprate in THF.106 The Grignard prepared above was added to the l L addition funnel in two aliquots. The Grignard was added to the reaction mixture at such a rate thate the internal temperature stayed between 5°C and 10°C. An additional liter of THF was used tO effect transfer Of the Grignard which had crystallized in the addition funnel upon cooling to room temperature. Two h after the last addition of the Grignard, about 1 L water was added, and the mixture separated in a 6 L separatory funnel. The THF layer was washed with water (2 x 500 mL), and the resulting mixture concentrated to give 950 g crude product. Careful distillation at atmospheric pressure through a 50 cm by 30 mm glass helices packed column gave a 142 g (24.5%) 6-methylheptyl bromide fraction distilling over at 174-176°c107 which was greater than 99% pure (g.c., NMR). Additional fractions cut from either Side of material which contained approximately 55% 6-methylheptylbromide (250 g, 43%) and could be 1 redistilled; H NMR (C0613) 6 0.85 (d, 6H, J = 6H2), 1.03 - 2.13 (br.m, 9H), 3.33 (t, 2H, J = 6H2). Preparation of tert-butyl-6-methylheptylsulfoxide (21). To a flame dried 3 L three necked round bottom flask, equipped with a mechanical stirrer, rubber septum, and nitrogen outlet tube, was added tolylsulfoxide (22, 20.1 g, 0.08 mol) dissolved in 2 L dry ether. The system was then cooled to -78°C in a dry ice / acetone bath. 177 mL of nggybutyllithium (1.8 M, 0.32 mole) was added (Slowly at first) to the solution by means of a canula which first went to a serum capped 122 graduated cylinder. The mixture was allowed to stir an additional three hours at -78°C, and the cold bath was then removed. Distilled water (300 mL) was added Slowly to quench the reaction mixture. Upon warming to 0°C to 10°C, the layers were separated, the ether layer extracted with water (150 mL), and the combined aqueous layers back-extracted with ether (3 x 100 mL). The ether extracts were combined, dried with sodium sulfate, concentrated, and further dried (0.5mm, 6 H) to give 98-105% Of 12:1:butylsulfoxide (21). In the next step, (21) is used without further purification, and should 322 be stored for extended periods Since it appears to be moderately unstable. Storage at 0°C for less than 24 h appeared to be acceptable. Preparation Of 7S,8S-2-Methyl-8-hygroxyoctadecan-7-yl-tert-butyl- sulfoxide (52a, cis precursor) and its diastereomer (52b, trans precursor, 72,8R). TO a flame dried 500 mL three necked flask equipped with a mechanical stirrer, rubber septum, and 125 mL addition funnel with a nitrogen outlet tube, was added crude Egrgrbutyl-6- methylheptylsulfoxide (21, 9.479, 0.0434 mol) in 130 mL of dry ether. The system was then cooled to -78°C in a dry ice / acetone bath. 23.9 mL gfbutyllithium (2.0 M in hexane, 10% excess) was added to the solution. The generated anion (color change from light yellow to dark yellow or yellow brown) was allowed to stir for 45 to 60 minutes, after which freshly distilled (54°C, 0.13 mm) undecanal (8.86 g, 0.521 mol, 20% excess) was added. The reaction mixture was allowed to stir for an additional 45-60 minutes. 100 mL of cold saturated ammonium chloride solution was added dropwise from the addition funnel. After addition was complete, the ice bath was removed. Upon warming to 0-10°C, the 123 phases were separated, the aqueous phase back-extracted with ether (2 x 100 mL) and the combined ether extracts dried with sodium sulfate. Concentration of the ether extracts gave 32.3 g crude product. Separation by column chromatography (silica gel ; ether) yielded 10.8 g (35% from 22) Of 222_(§1§ precursor) and 13.9 g (45% from 22) of 222_ (trans precursor) . Preparation of 7S,2S-2-methyl-8-hydroxyoctadecan-7-yl-tert-butylsulfide (22, cis precursor). TO a one necked 500 mL round bottom flask, equipped with a West condenser topped with an addition funnel, was added 222_(20.0 g, 51.4 mmol) in 150 mL of dry tetrahydrofuran. The system was cooled to -78°C, and sodium bis(methoxyethoxy)aluminum hydride (40.0 mL, 80% solution in benzene) in 100 mL dry THF was added in a dropwise fashion over a period Of two h. The system was allowed to warm to room temperature over a half h period, and then warmed to 68°C for at least eight h. The aqueous layer and resulting salts were extracted with additional benzene (3 x 300 mL), the combined extracts dried with magnesium sulfate, concentrated, and purified by column chromatography (silica gel ; benzene) to give 15.5 g (81%) of 22, which Should be at least 95% pure (222_t.1.c. spot). Preparation Of (+)-disparlure (54), TO a one necked 500 mL round bottom flask was added 22 (10.0 g, 28.6 mmol) and 100 mL Of solvent (methylene chloride : nitromethane ; 1:1) under nitrogen. After cooling to 0°C, trimethyloxonium tetrafluoroborate108 (7.94 g, 53.7 mmol) was added, and the system allowed to vigorously stir for l h and 10 min. The solvent was then removed by distillation, with the temperature not rising above 25°C. The total reaction time should not exceed 2 h. Dichloromethane 124 (200 mL) and 0.5 N sodium hydroxide (200 mL) were then added to the reaction flask, and allowed to stir moderately vigorously for 10-12 h. The reaction mixture was allowed to separate, and the aqueous layer was extracted with dichloromethane (3 x 200 mL), and the combined extracts filtered through a 60 x 20 mm plug of silica BEFORE concentration.109 After concentration, the material was chromatographed (silica gel ; benzene) to give 4.43 g (58.4%) of 23, This material was distilled to remove a very minor yellow impurity (molecular distillation, 110°C, 0.5 mm), and the resulting disparlure determined to be at least 99% pure by t.1.c. and v.p.c. REFERENCES (7) (8) (9) (10) (ll) (12) 126 REFERENCES C.J. Pederson, J. Am. Chem. Sbc., 22, 7017 (1967). C.J. Pederson, Aldrichimica Acta, 2, 1 (1971). For some reviews of crown ether chemistry see (a) C.J. Pederson and H.K. Frensdorf, Angew. Chem., Int. Ed. EngZ., 11, 16 (1972); (b) 0.0. Christensen, D.J. Eatough, and R.M. Izatt, Chem. Rev., 22, 351 (1974); (c) 0.3. Cram and J.M. Cram, Science, 122, 803 (1974); (d) J.-M. Lehn, Structure and Bonding (Berlin), 12, 1 (1973); (e) G.W. GOkel and H.D. Durst, synthesis, 168 (1976); (f) G.W. Gokel and H.D. Durst, Aldrichimica Acta, 2, 3 (1976). 0.0. Sam and H.E. Simmons, J. Am. Chem. Soc., 22, 4024 (1972). C.L. Liotta and H.P. Harris, J. Am. Chem. 500., 22, 2250 (1974). (a) J.S. Valentine and A.B. Curtis, J. Am. Chem. Soc., 22, 224 (1975); (b) E.J. Corey, K.C. Nicolaou, M. Shibassaki, Y. Machida, and C. Shoner, Tetrahedron Lett., 83 (1975). R.A. Bartsch, Acc. Chem. Res., 2, 239 (1975). R. Boden, Synthesis, 783 (1975). (a) R.A. Bartsch, H. Chen, N.F. Haddock, P.N. Juri, J. Am. Chem. Soc., 22, 6753 (1976); (b) Samples Of crowns 2, 2, and 2, given to Dr. Bartsch have been found to inhibit the reactions of aryl diazonium salts to some degree. R. A. Bartsch, presented in part at the First and Second Symposium on Macrocyclic Compounds, Provo, Utah, August 1977 and 1978. 0.0. Cram and J.M. Cram, Acc. Chem. Res., 11, 8 (1978). 0.0. Cram, R.C. Helgeson, L.R. Sousa, J.M. Timco, M. Newcomb, P. Moreau, F. DeJong, G.W. Gokel, D.H. Hoffman, L.A. Domier, S.C. Peacock, K. Madan and L. Kaplan, Pure and Applied Chem., 22, 327 (1975). (a) L.R. Sousa and J.M. Larson, J. Am. Chem. Scc., 22, 307 (1977); (b) L.R. Sousa, J.M. Larson and H.S. Brown, submitted for publication. (13) (15) (16) (17) (l8) (19) (20) (21) 127 (a) J.M. Larson and L.R. Sousa, J. Am. Chem. 800., 122, 1943 (1978); (b) J.M. Larson and L.R. Sousa, results with crown 2_ were presented in part at the 174ED-National Meeting Of the ACS, Chicago, Illinois, August 1977; (c) J.M. Larson and L.R. Sousa, results with crowns 2, 2, and 2 were presented in part at the First Symposium on Macrocyclic Compounds, Provo, Utah, August 1978. James M. Larson, "Investigation of the Perturbation Of the Excited State Processes of Naphthalene Crown Ether Derivatives by Complexation Of the Cations Of Alkali Metal Chlorides, Barium Bromide, and Silver Triflate; Investigation Of the External Heavy Atom Perturbation of the Excited State Processes Of Naphthalene Crown Ether Derivatives by Ethyl Bromide and by Means of Complexed Haloalkylammonium Cations", Ph. D. Dissertation, Michigan State University, 1979. L.R. Sousa and M.R. Johnson, J. Am. Chem. Soc., 122, 344 (1978); (b) L.R. Sousa, M.R. Johnson and H. S. Brown, Second Symposium on Macrocyclic Compounds, Provo, Utah, August 1978. Mark R. Johnson, "Part 1: Heterocyclic Photochemistry: The Photochemical Synthesis Of B-Lactams; Part 2: The 13C NMR Spectra Of Naphthalene Crown Ether Complexes: Field Induced n- polarization and Crown Ether Conformational Changes", Ph.D. Dissertation, Michagan State University, 1978. D.L. Ward, H.S. Brown and L.R. Sousa, submitted for publication. D.L. Ward, H.S. Brown and L.R. Sousa, Acta Cryst., 222, 3537 (1977). (a) J.M. Timko, R.C. Helgeson, M. Newcomb, G.W. Gokel and D.J. Cram, J. Am. Chem. Sbc., 22, 7097 (1974); (b) D.N. Reinhoudt and R.T. Gray, Tetrahedron Lett., 2015 (1975); (C) D.N. Reinhoudt, R.T. Gray, C.J. Smit and I. Veenstra, Tetrahedron, 1161 (1976); (d) M. Newcomb, G.W. Gokel and D.J. Cram, J. Am. Chem. Soc., 22, 6810 (1974); (e) F. Voetgle and M. Zuber, Tetrahedron Lett., 561 (1972). R.N. Green, Tetrahedron Lett., 1793 (1972). H.J. Dauben, Jr. and L.L. MCCOy, J. Am. Chem. Sbc., 21, 4863 (1959). (22) (23) (24) (27) (31) (32) (33) (34) (35) (36) (37) (38) (39) 128 E.D. Bergmann and J. Szmuszkovicz, J. Am. Chem. Soc., 22, 2760 (1953). T.A. Geissman and L. Morris, J. Am. Chem. Soc., 22, 716 (1944). V.M. Micovic and M.LJ. Mihailovic, J. Org. Chem., 12, 1190 (1953). K.J. Laidler, "Chemical Kinetics", Mc Graw-Hill, Inc., New York, 1965, p89. 2en20phenone 1etracarboxy1ic 2ignhydride. A one pound sample Of this material was generously donated by Gulf Chemicals, Houston, Texas. N.L. Mosby, J. Am. Chem. Sbc., 22, 3600 (1953). This sample of l,4,5,8-tetramethyl naphthalene was provided by Mr. David Makowski in Dr. H. Hart's group. It's origin is unknown to this author, although it's preparation iS in the literature. J. Mosby, J. Am. Chem. Soc., 22, 2564 (1952). Lumilux is the brand name for a fluorescent indicator used in UV- 254 sorbants, and is currently marketed by Brinkmann Instruments. For recent reviews, see (a) N.K. Dalley, "Synthetic Multidentate Macrocyclic Compounds", Progress in Macrocyclic Chemistry, 1, Academic Press, Inc., New York, 1978, Chapter 4; (b) M.R. Truter, Structure and Bonding (Berlin). 12, 71 (1973). M.A. Busch and M.R. Truter, J.C.S. Chem. Comm., 1439 (1970). M.R. Truter, Personal Communication, August 1977, Provo, Utah. D. Live and S.I. Chen, J. Am. Chem. Soc., 22, 3769 (1976). The numbering scheme was chosen for simplicity and convenience, and is not consistent with I.U.P.A.C. nomenclature rules. Ref. 30(a), p208. 0. Bright, I.E. Maxwell, and J. deBoer, J.C.S. Perkin II, 2101 (1973). J.-B. Robert, J.S. Sherfinski, R.E. Marsh, and J.D. Roberts, J. Org. Chem., 22, 1152 (1974). J. Handal, J.G. White, R.W. Franck, Y.H. Yuh, and N.L. Allinger, J. Am. Chem. 800., 22, 3345 (1977). "Tables Of Interatomic Distances and Configuration in Molecules and Ions", Spec. Publ. NO. 18, The Chemical Society, London (1960). (46) (47) (48) (49) (50) (51) (52) (53) (54) (55) (56) (57) (53) (59) 129 M. Davis and O. Hassel, Acta Chem. seand., 12, 1181 (1963). J.D. Dunitz, M. DObler, P. Seiler, and R.P. Phizackerley, Acta Cryst., 222, 2733 (1974). (a) M. Mercer and M.R. Truter, J. Chem. Soc., Dalton Trans., 2215, (1973); (b) M. Mercer and M.R. Truter, J. Chem. Soc., Dalton Trans., 2469, (1973). (a) I. Goldberg, Acta Cryst., 221, 754 (1975); (b) I. Goldberg, Acta Cryst., 221, 2592 (1975); (c) I. Goldberg, Acta Cryst., 222, 41 (1976). K.-T. Wei and D.L. Ward, Acta Cryst., 222, 2768 (1976). G. Germain, P. Main and M.M. Woolfson, Acta Cryst., A22, 368 (l97l). C.K. Johnson, ORTEP, Report 0RNL-3794, Oak Ridge National Laboratory, Oak Ridge, Tennessee (1965). These programs were acquired from Dr. Allan Zalkin by Dr, Donald Ward, and modified for use on the MSU CDC-6500. P.A. Doyle and P.S. Turner, Acta Cryst., 222, 390 (1968). R.F. Stewart, E.R. Davidson and W.T. Simpson, J. Chem. Phg8.,fl2. 3175 (1965). 0.1. Cromer and D. Liberman, J. Chem. Phys., 22, 1891 (1970). T. Foerster, Discussions Faraday SOc., 22, 7 (1959). For a good general discussion on energy transfer, see A.A. Lamola and N.J. Turro, "Energy Transfer and Organic Photochemistry", Technique of Organic Chemistry, Volume XIV, Interscience division of John Wiley and Sons, New York, 1969. O. Schaepp and M. Levy, J. Am. Chem. soc., 22, 172 (1962). A.A. Lamola, P.A. Leermakers, G.W. Byers, and 0.5. Hammond, J. Am. Chem. Sbc., 22, 2322 (1965). H. Hart, J.L. Reilly, and J.B.-C. Jiang, J. Org. Chem., 52, 2684 (1977). These spectra are in the possession of Dr. L.R. Sousa. R.A. Keller and L.J. Dolby, J. Am. Chem. soc., 22, 2768 (1967). V.M. Berenfeld and V.A. Kroagauz, Izu. Akad. Nauk., SSSR, Ser. Fiz, 22, 1575 (1968). Sandra E. Klassen, "Synthesis of 3,4-(20-Crown-6)BenZOphenone: A Potential Selective Triplet Sensitizer", H.S. Thesis, Michigan 130 State University, 1976, p37. (60) E.J. Corey and J.W. Suggs, Tetrahedron Lett., 2647 (1975). (61) 8121'va p454. (62) T.J. Kealy and P.L.Pauson, Nature, 122, 1039 (1951). (63) S.A. Miller, J.A. Tibboth, and J.F. Tremaine, J. Chem. Soc., 632 (1952). (64) D.E. Bub1itz and K.L. Rhinehart, Jr., Organic Reactions, 12, 1 (1969), and 40 references to reviews contained therin. (65) F.A. Cotton and G. Wilkenson, "Advanced Inorganic Chemistry, Third Edition", John Wiley and Sons, New York, 1972, p737. (66) G. Wilkenson, M. Rosenblum, M.C. Whiting and R.B. Woodward, J. Am. Chem. Sbc.,‘22, 2125 (1952). (67) (a) R.B. Woodward, M. Rosenblum and M.C. Whiting, J. Am. Chem. soc., 22, 3458 (1952); (b) A.N. Nesmeyanov, E.G. Perevalouva and Z.A. Beinoravichute, Proc. Acad. Sci., USSR, 112, 439 (1957). (68) M.D. Rausch and D.J. Ciappenelli, J. Organometal. Chem., 12, 127 (1967). (69) N.M. Yoon, C.S. Pak, H.C. Brown, S. Krishnamurthy and T.P. Stocky, J. Org. Chem., 22, 2786 (1973). (70) S.I. Go1dberg, J. Org. Chem., 22, 482 (1960). (71) F.H. Stodola, J. Org. Chem., 22, 2490 (1964). (72) Some preliminary equilibrium constant measurements on 1,1'- ferrocene-lB-crown-S (22) in ethanol show the equilibrium constant with potassium tO be about 400, deSpite the fact that CPK models Show a good fit for potassium in this crown. (73) M. Rosenblum and R.B. Woodward, J. Am. Chem. Sbc., 22, 5443 (1958). (74) A.N. Nesmeyanov, E.G. Perevalova, R.V. Golovnya and 0.A. Nesmeyanova, Dokl. Akad. Nauk. SSSR, 22, 459 (1954). (75) This A/D interface was designed and built by Mr. Martin Rabb and Dr. Thomas Atkinson, Department Of Chemistry, Michigan State University. (76) "05/8 Handbook", Digital Equipment Corporation, Maynard, Massachusetts, p8-2. (77) Ref. 76, p1-108. (78) Software was written in PAL8 by Dr. Thomas Atkinson with help (79) (80) (81) (82) (83) (84) (85) (86) (92) (93) (94) (95) (95) 131 (and encouragement) from this author. The PROM was programmed on a PDPll/40 by Dr. Thomas Atkinson and Mr. Timothy Kelly. B.K. Hahn and C.G. Enke, Anal. Chem., 22, 651A (1973). P.J. Wagner, private communication. This program uses the method of J.A. POple, D.L. Beveridge, and P.A. Dobash, J. Chem. Phys., 22, 2026 (1967). M. Beroza and E.F. Knipling, science, 122, 19 (1972). F. Acree, Jr., M. Beroza, R.F. Holbrook, H.L. Haller, J. Econ. Entomol., 22, 943 (1970). B.A. Bierl, M. Beroza, and C.W. Collier, science, 122, 87 (1970). (a) H.J. Bestmann and O. Vostrowsky, Tetrathedron Lett., 207 (1974); (b) H.J. Bestmann, 0. Vostrowsky and W. Stramsky, Chem. Ber., 122, 3375 (1976). K. Kluenenberg and H.J. Schafer, Angew. Chem. Int. Ed. Engl., 12, 47 (1978). R.T. Carde, C.C. Doane, T.C. Baker, 5. Iwaki and S. Marumo, Environ. Entomol., 2, 768 (1977). For a very good review on the "Synthesis Of Chiral Components of Insect Pheromones" including disparlure, see R. Rossi, Synthesis, 413 (1978). S. Iwaki, S. Marumo, T. Saito, M. Yamada and K. Katagiri, J. Am. Chem. Sbc., 22, 7842 (1978). Structure proof through optical rotations alone were almost impossible due to the small magnitude Of the rotation compiled with the low yield Of pheremone from the insects. K. Mori, T. Takigawa and M Matsui, Tetrahedron Lett., 3953 (1976). (a) W.H. Pirkle and P.L. Rinaldi, J. Org. Chem., 22, 1025 (1979); (b) W.H. Pirkle and P.L. Rinaldi, J. Org. Chem., 22, 3803 (1978). 0.0. Farnum, T. Vesoglu, A.M. Carde, B. Duhl-Emswiler, T.A. Pancoast, T.J. Reitz, and R.T. Carde, Tetrahedron Lett., 4009 (1977). Comercially available from Pfaltz and Bauer, Inc. L. Friedman and A. Shani, J. Am. Chem. soc., 22, 7101 (1974). 132 (a) M. Tamura and J.K. Kochi, synthesis, 303 (1971); (b) J. Millon and G. Linstrume11e, Tetrahedron Lett., 1095 (1976). H.D. House, "Modern Synthetic Reactions, Second Edition", W.A. Benjamin, Inc., Menlo Park, California, 1972, p631, 672, and references cited therin. Sodium 212(methoxyethoxy)aluminum hydride is sold by Columbia Organic Chemicals as "Vite", by Aldrich Chemicals as "Red-Al", and by Eastman Organic Chemicals as "Vitride". T. H0 and C.M. Wong, Org. Prep. and Proc., 2, 163 (1975). H.D. Durst, J.W. Zubrick and G.R. Kieczykowski, Tetrahedron Lett., 1777 (1974). J.R. Shanklin, C.R. Johnson, J. Ollinger and R.M. Coates, J. Am. Chem. Sbc., 22, 3429 (1973). J.E. Baldwin, R.E. Hackler and D.P. Kelly, J. Am. Chem. Soc., 22, 4758 (1968). (a) R.W. Alder, Chem. Ind., 983 (1973); (b) Anja Carde, private communication. D.G. Farnum et al.. manuscript in preparation. M. Tamura and J. Kocki, synthesis, 303 (1972). At this point, fractions were being cut every 25 mL, and each was checked by g.c.. T.J. Caurphey, Org. syn., 21, 142 (1971). Extensive destruction Of disparlure will occur at room temperature over an eight hour period if this is not done immediately. APPENDIX A 134 LISTING OF INTEREFACE PROGRAM WRITTEN IN BASIC PAGE 1 100 PRINT PNT(26) 110 PRINT "PDP‘B HITACHI INTERFACE PROGRAM,"; 120 PRINT " VERSION 2.5-NA" 130 PRINT "FOR BASIC VERSION h. 0, OS- 8 3C" 1&0 PRINT "WRITTEN BY: HOUSTON S. BROWN" 150 PRINT " : DEPARTMENT OF CHEMISTRY" 160 PRINT " :MICHIGAN STATE UNIVERSITY" 170 PRINT " : COPYRIGHT @ 1977" 180 PRINT " : BY THE L.R. SOUSA GROUP" 190 PRINT " : AND THE BOARD OF REGENTS" 200 UDEF INI(N),PLY(Y),DLY(N),DIS(S,E,N,X) 210 UDEF SAM(C,N,P,T),CLK(R,O,S),CLW(N),ADC(N) 220 UDEF GET(M,L),PUT(M,L),DR|(N),DRO(M,N) 230 $0=1 240 J=1 250 19=1 260 DIM A(400) 270 DIM 8(10) 280 DIM C(100) 290 USE A 300 USE B 310 USE C 320 Hh=120 330 PRINT "RESTART (Y OR N)"; 340 INPUT Q$ 350 IFQ$="N” GO TO AND 360 IF Q$<>"Y" GO TO 330 370 FILE#1:"FLPO:AREAS." 380 INPUT #1:J,A1,A2 390 FOR |=1 TO J 400 INPUT #1:C(l),A1,A2 410 NEXT 1 420 CLOSE #1 430 J=J+1 440 PRINT PNT(7) 450 19=1 460 X=1Nl(0) 470 Zl=-300 480 22=-300 490 23=-300 500 A$="FLP1:" 510 B$="DATA" 520 E$=".DA" 530 D$=STR$(J) 540 PRINT "RUN # "&D$; 550 INPUT A1 560 IF A1=IO GO TO 1290 1270 |9=| 1280 IO=A(I) 1290 NEXT I 1300 FOR I=1 TO H3 1310 A(I)=A(|)-IO 1320 NEXT I 1330 19=(19/2)+H1-0.5 1340 PRINT "LOW POINT AT "&STF$(19)&" AM" 1350 JZ=I9 1360 J3=19 1370 J4=|9 1380 PRINT "START INT AT THIS LBA"&STR$(J1); 1390 INPUT A1 1400 IF A1=-100 GO TO 1380 1410 IF A1<0 GO TO 440 1420 IF A1=0 GO TO 1440 1430 Jl=A1 1440 PRINT "END INT AT THIS LBA"&STR$(02); 1450 INPUT A1 1460 IF Al=-100 GO TO 1380 1470 IF A1