A STUDY OF SOME FIVE-MEMBERED OXYGEN HETEROCYCLES DISSERTATION Presented in Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the Graduate School of The Ohio State U n iv e rsity By CARL HENRY SNYDER, B.S. in Chem. The Ohio S ta te U n iv e rsity 1958 Approved by r 1 . A dviser1 a v» ! Department of Chemistry ACKNOWLEDGMENT I wish to thank Professor Melvin S. Newman for his suggestion of this problem and for his guidance throughout the work presented in this dissertation. My thanks are also givaa to the other members of the Chemistry Department and to my fellow graduate students for allowing me free use of their time, chemicals, and equipment. I wish to express my gratitude to the Kettering Foundation for fellowships granted during the years 1954-1957- Finally, I wish to thank my wife, Jean, for her sympathy and understanding throughout this work. i i TABLE CSP CONTENTS INTRODUCTION.......................................................... ....................................................1 HISTORICAL.......................................................................................................................7 Investigations Involving Vinylene Carbonate. 7 3”dioxolane (V) ............................................. 8 PROPOSED PLAN OP RESEARCH.............................................................................11 Investigations Involving Vinylene Carbonate. 11 4.5-Dimethylene-l,3-dioxolane (V) ........................................ 12 NOMENCLATURE...............................................................................................................15 STRUCTURE ................................................................................................................15 RESULTS AND DISCUSSION ................................................................................... 16 Investigations Involving Vinylene Carbonate. 16 4.5-Dimethlene-1,3-dioxolane (V) .......................................... 23 EXPERIMENTAL................................................................................................................52 Investigations Involving Vinylene Carbonate. 53 4.5-Dime thylene-1, 3-dioxolane .......................................................57 SUMMARY...............................................................................................................................93 AUTOBIOGRAPHY................................................................................................................95 i i i LIST OF TABLES Table 1 Results of Diels-Alder Additions of Vinylene Carbonate and F u ran .........................................................17 2 Reduction of XXI to XXII with Lithium Aluminum Hydride in Tetrahydrofuran ............................................. 35 3 Fractionation of XVI .......................................................................................... 39 4 Fractionation of XXII ....................................................... .....71 5 Fractionation of XXV .......................................................................................... 85 iv LIST OF FIGURES F ig u re 1 Synthetic Approaches and Structure Proof for 4,5-Dimethylene-1,3-dioxolane ............................................... 25 2 4>5-DImethylene-l,3-dioxolane ......................................................... 76 3 Hydrocarbon-soluble Portion of Bis- (amine oxide) (XXIII) Pyrolysate ............................... 80 4 Slower-moving Chromatographic Band ..................................................80 5 Faster-moving Chromatographic Band .................................................. 81 6 Material Extracted from Column below Lower B a n d ...............................................................................................................8l 7 Compound XXIX ( U ltr a v io le t S p ectru m ) ............................................. 84 8 Product Obtained from Pyrolysis of d- 4,5-Bis-(hydroxymethyl)-1,3-^ioxolane Diacetate . 89 9 N-Phenylmaleimide (Ultraviolet Spectrum) ...................................9° 1 0 Compound XXIX (in f r a r e d S p e c tr u m ) ...................................................91 11 N-Phenylmaleimide (infrared Spectrum) ..................................... 91 12 Compound XXVT .......................................................................................................92 13 4 ,5 -D im e th y l-l, 3-d io x o la n e ........................................................................92 v INTRODUCTION Inositols are naturally occurring 1,23 33k,5,6- hexahydroxycyclohexanes, which are capable of existence in nine stereoisomeric forms as follows (the substituent -OH is indicated by a vertical line): 1 2 3 4 5 6 7 8 The ninth configuration is the optical antipode of struc­ tu re 7 • One of the most interesting of these is mesolnositol (structure 5)* a growth stimulant for yeast. The original objective of this research was to synthesize mesolnositol. An interesting starting material for this synthesis was the DIels-Alder adduct (i) of furan and vinylene carbonate (l). (1) M. S. Newman and R. Addor.* J. Am. Chem. Soc.* 77j 3792(1955). 1 It was felt that since synthesis might involve several steps, the yield of I, reported as 3 should be improved. Furthermore, because of interest in syntheses involving vinylene carbonate, attempts were directed toward preparation of IV, an Interesting heterocyclic compound. The path chosen involved protection of the double bond of vinylene carbonate by Diels-Alder addition to anthracene, hydrolysis of the car­ bonate moiety, formal formation and pyrolytic reversal of the Diels-Alder reaction: Because of a continuing interest in Diels-Alder reactions, thought was also given toward design of a diene which might prove the most reactive Diels-Alder diene known. To satisfy conditions necessary for diene reactivity (l) the (l)M.C. Kloetzel, "Organic Reactions," Vol. 4, John Wiley and Sons, New York, 1948, p. 1. proposed diene should: 1. contain electron-donating groups adjacent to the diene moiety, 2. contain els-fused, conjugated, terminal methylene groups, and 3» be planar. The simplest structure satisfying these three criteria is 4,5-dimethylene-l,3-dloxolane (v ): CH V This planar structure contains a 1,3-butadiene moiety, cis- fused by a 5-membered ring and vinylic to the electron- donating heterocyclic oxygens. If the synthesis of V were successful, addition of the diene to di-t-butylaeetylene might prove an important step leading toward a synthesis of 3*4-di-t-butylphenol (Vi) (R represents -c(CH ) ): v 3 3 a c a cill -h R ft V Hz ° R ✓ ~~ 'OH ft VI A study of the equilibrium between VI and Its quinoidal form (VII) : a f t f t H VI VII should prove interesting since the equilibrium might favor VII for relief of steric strain caused by eclipsing of the two t-butyl groups In VI. 5 The diene (V) contains several desirable features for the synthetic route described. First, the 1,3-dioxolane moiety is actually a formal and should be hydrolyzed easily. Also, the cis-fused butadiene moiety is held in the configur­ ation necessary for Diels-Alder addition. Finally, V should offer very little steric resistance to addition. The planarity of the molecule should allow intimate approach to the dienophile for formation of an intermediate ionic com­ plex (l) , and the terminal methylene groups should be ( 1 )I b i d . sterically free to add. That steric factors are operative in the Diels-Alder reaction is borne out by the fact that perchlorocyclopentadiene, a very reactive diene, does not undergo addition with di-t-butylacetylene or a 1:1 mixture of cis- and trans-dl- 1-butylethylene ( 2) although it adds to k- (2)W. H. Puterbaugh, Thiele College, Greenville, Pa.; private communication. methyl-2-pentene and 3,3-dlmethyl-l-butene ( 3) . T his i s (_3)H. E. Ungnade and E. T. McBee, Chem. Rev., £ 8, 2^9 (1958)j C. Berger and 0. Becker, Z. Naturforsch, 9b, 584 U954). probably due to extreme steric oppositions between the two t- butyl groups and a chlorine atom of the ^CClg bridge - Since the present research involves two general areas of interest--investigations involving vinylene carbonate, and synthesis of 4, 5~dimethylene-l, 3~dioxo.lane--future dis­ cussions of this research will be in the order: 1. investigations involving vinylene car­ bonate., and 2. 4,5-dimethylene-l, 3-dioxolane. HISTORICAL Investigations Involying Vinylene Carbonate The only reported Investigation of vinylene carbonate pertinent to the present work Involves a synthesis of alioinositol (structure 3* P* l) In 20$ overall yield from vinylene carbonate and trans,trans-diacetoxybutadlene (l): (l)R. Criegee and P. Becher, Ber., 9°> 2516 (1957)* CH C Ox P., CCH CCH3 OsO, PH Bo. (OH) "L V/ alloinosltol H A reported yield of 31$ In the Diels-Alder reaction compares well with the yield reported by Newman and Addor (2) for the (2)M. S. Newman and R. Addor, loc. c it. Diels-Alder addition of vinylene carbonate and furan. Although many substituted dioxole derivatives have been reported, the parent heterocycle itself is unknown 4,5-Plmethylene-lj3-dioxolane (v) The synthesis of V by the route shown below has been r e p o r te d ( 1): (l)M. R. Radcliffe and W. G. Mayes (to Firestone Tire & Rubber Company), U. S. patent 2,445,733, July 20, 1948. CH, C| CH-OH l * CH-OH Cm Cl VIII IX V Very little evidence for the proposed structure (v) was given in the patent. Aside from a boiling point (115-116°) and a brief report of polymerization studies, the most important information supporting