THE SYNTHESES OF THE ENEQTIPFEEGEECYM REE-Km §Y$WM W MEMQS SF 11% @s‘EELS-xALBER fiACTEGN Thefls ‘50.: FM Daqvce of‘ D5. Du MECEEGM‘! STATE UNEVERSETY Robert Eugene McC-Omb 196:? LIBRARY Michigan State University This is to certify that the thesis entitled THE SYNTHESIS OF THE ENDOTHIOBICYCLO RING SYSTEM BY MEANS OF THE DIELS-ALDER REACTION presented by ROBERT EUGENE MCCOMB has been accepted towards fulfillment of the requirements for M degree in _Ch_e_m_i§_tr Y fi>4 R.” /X((/:L‘ / i; ,,// ,/ ____ // 0-169 ARY 1 State ABSTRACT THE SYNTHESIS OF THE ENDOTHIOBICYCLO RING SYSTEM BY MEANS OF THE DIELS-ALDER REACTION BY Robert Eugene McComb The present investigation was undertaken with two main objectives; namely, to develop synthetic procedures for the synthesis of endothiobicyclo compounds wherein a sulfur atom bridges a six membered ring at the 1,4—positions and to investigate their chemical and physical properties. Attempts to synthesize 1-hydroxy—7-thiobicyclo[2.2.1]- heptane were unsuccessful. OH HO]. ArSOaI-Ia (C: RcoaHa gm C1 CHs-E-SH 01’ OH s-c- -CH3 s_E'.. ms + KOH ROH Robert Eugene McComb However, from this series of reaction a new compound; 4-chlorocyclohexene oxide (4-chloro-7—oxo—bicyclo[4.1.0]heptane) was obtained. Efforts to prepare 1,4-thianaphthalene[1,4—endothionaph— thalene] by the reaction of sulfur with i-nitronaphthalene by the Herzfelder method (5) were also unsuccessful. N02 The next eXperimental approach to obtaining the endo- thiobicyclo compound was by a Diels Alder type reaction using 5,4-disubstituted thiophene and thiophene with very reactive dienophiles such as tetracyanoethylene and benzyne. A number of 5,4-disubstituted thiophenes were made as inter- mediates for the series of Diels Alder reactions; 5,4- dimethyl-, 5,4-dimethoxy-, 3,4-diphenylthi0phene, 4,5,6,7- dibenzoisothionaphthalene and 4,5,6,7—tetrahydrobenzo[C]— thiOphene(5,4-tetramethy1enethiophene). The re—evaluation of thiophene as a diene in the Diels Alder reaction was undertaken. Attempts to react thiophene with acrylonitrile, acrylic acid, methyl acrylate, dimethyl acetylenedicarboxylate, acetylene dicarboxylic acid, maleic anhydride and tetracyanoethylene under a variety of reaction conditions were unsuccessful. Attempts to interact 3,4- dimethyl-, 5,4-dimethoxy-, and 3,4-diphenylthiophene with Robert Eugene McComb maleic anhydride and tetracyanoethylene under various experi— mental conditions were also unsuccessful. The 4,5,6{Fdibenzoisothionaphthalene and 4,5,6,7—tetra— hydrobenzo[C]thiophene both reacted with maleic anhydride and tetracyanoethylene to give the following products; 5,6,7,8-dibenzo—1,2,3,4-tetrahydro—1,4-endothionaphthalene- (2,5) anhydride (9), naphthalene, C49 \ I [ :‘ 6/0 . \ a \O 1,2,5,4,5,6,7,8-octahydro-1,4-endothionaphthalene(2,5)anhydride and Robert Eugene McComb 1,4,5,6,7,8-hexahydro—2,2,3,S-tetracyano—i,4—endothionaph— thalene. The last series of reactions investigated was the re— action of benzyne with thiophene and/or its derivatives; 5,4-dimethy1-, 5,4-dimethoxy-, and 3,4-diphenylthi0phene. The 5,4-disubstituted thiophenes reacted with benzyne but attempts to isolate the 2,5-disubstituted-1,4—dihydro-i,4-o endothionaphthalene products were unsuccessful. Thiophene did react with benzyne to yield several products; 2- and 5-phenylthi0phene, 2,5-, 2,4—, 2.5-, and 5,4-dipheny1thi0phenes were isolated in small yields. The 1,4-dihydro-1,4-endothionaphthalene (m.p. 78.5—80.00) was isolated (6 to 13%) and characterized. It was found to be very unstable at ambient conditions. Its stability was improved by storing it below 00 (2-5 months). The final two disubstituted thiOphenes, 4,5,6,7-dibenzo- isothionaphthalene and 4,5,6,7-tetrahydrobenzo[C]thiophene, were reacted with benzyne to give the following products, 0«we Robert Eugene McComb 6,7,8,9-dibenzo-5,10-dihydro-5,10-endothioanthracene which appears to be very stable at ambient conditions and 5,6,7,8,9,iO—hexahydro-Q,iO—endothioanthracene which also appeared to be stable at ambient conditions. THE SYNTHESIS OF THE ENDOTHIOBICYCLO RING SYSTEM BY MEANS OF THE DIELS-ALDER REACTION BY Robert Eugene McComb A THESIS Submitted to Michigan State University in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY Department of Chemistry 1969 /<7N40/ 2/ ’ ACKNOWLEDGMENTS The author would like to express his appreciation to Professor Robert D. Schuetz for his guidance, understand- ing and friendship throughout the course of this work. He wishes to express his thanks to his wife, Kathleen, for her patience, understanding and encouragement throughout this study. ii VITA Robert Eugene McComb Date and Place of Birth: April 20, 1928 in Lansing, Michigan Education: Public School, Grand Ledge, Michigan Graduated from Grand Ledge High School, June 1946 Kenyon College Gambier, Ohio Artus Bacholorius (Chemistry) June 1955 Michigan State University, East Lansing, Michigan Midland Extension 1954-1956 In Residence 1956-1957 Master of Science (Organic Chemistry) December 1957 Professional Positions Analytical Chemist, The Dow Chemical Company ‘Midland, Michigan, July 1952 to September 1956 Graduate Teaching Assistant, Michigan State University, Chemistry 1956—1959 Analytical Chemist, Michigan State Highway Research Laboratories, East Lansing, Michigan June 1959 to February 1962 Organic Chemist, Department of Biochemistry Michigan State University, February 1962 to September»1962 Senior Research Chemist, Hercules Incorporated .Allegany Ballistic Laboratories, Cumberland, (Maryland, September 1962 to July 1966 Senior Research Chemist and Senior Engineer Specialist, Goodyear Aerospace Corporation, Akron, Ohio, July 1966 to December 1967 iii Senior PrOpellant Research Chemist, Head of Solid Propellant Research, Atlantic Research Corporation, Division of Susquehanna Corporation, Alexandria Virginia, December 1967 to present. Professional and Honor Societies American Chemical Society The Society of Sigma Xi iv TABLE OF CONTENTS Page INTRODUCTION. . . . . . . . . . . . . . . . . . . . . 1 HISTORICAL. . . . . . . . . . . . . . . . . . . . . . 5 DISCUSSION. . . . . . . . . . . . . . . . . . . . . . 15 EXPERIMENTAL. . . . . . . . . . . . .... . . . . . . 56 Attempted Preparation of 1-Hydroxy-7-thiabicyclo- [2.2.1]heptane . . . . . . . . . . . . . . . . . 56 Preparation of 4-Chlorocyclohexanol (II) . . . . 57 Preparation of 4-Chlorocyclohexene (III) . . . . 57 Preparation of 4-Chlorocyclohexene Oxide (IV). . 57 The Second Preparation of 4-Chlorocyclohexene Oxide (IV) [5-Chloro-7-oxabicyclo[4.1.0]heptane) 59 Reaction of 4-Chlorocyclohexene Oxide (IV) with Thioacetic Acid. . . . . . . . . . . . . . . . . 4O Attempted Preparation of 7-Thiabicyclo[2. 2.1]- heptanol . . . . . . . . . . . . . . . . . . . 42 Attempted Preparation of 1,4-Thionaphthalene by Herzfelders Method . . . . . . . . . . . . . . . 45 Second Attempt to Prepare 1,4-Thionaphthalene. . 46 The Preparation of 5,4-Disubstituted Thiophenes. 48 Preparation of Ethyl Thioglycolate . . . . . . . 48 Preparation of Diethyl Thiodiglycolate . . . . . 49 Preparation of Disodium Salt of 2,5-Dicarbo- methoxy-S,4-dihydroxythi0phene . . . . . . . . . 49 TABLE OF CONTENTS - Continued Page Preparation of 5,4—Dimethoxy-2,5-dicarbo- methoxythiophene. . . . . . . . . . . . . . . . 49 Preparation of 5,4-Dimethoxythi0phene . . . . . 50 Preparation of 5,4-Dipheny1-2,5-dicarboxythio- phene . . . . . . . . . . . . . . . . . . . . . 50 Preparation of 5,4-DiphenylthiOphene. . . . . . 51 Preparation of 5,4-Dimethy1-2,5-dicarboxythio- phene . . . . . . . . . . . . . . . . . . . . . 51 Preparation of 5,4-Dimethylthi0phene. . . . . . 52 Preparation of 4,5,6,7-Dibenzoisothianaphtha— lane-1,5-dicarboxylic.Acid. . . . . . . . . . . 52 Preparation of 4,5,6,7-Dibenzoisothianaphtha- lene. . . . . . . . . . . . . . . . . . . . . . 55 Preparation of 4,5,6,7-Tetrahydro-1,5-dicarboxy- benzo[C]thiophene (5,4—tetramethylene—2,5- dicarboxythiophene) . . . . . . . . . . . . . . 55 Preparation of 4,5,6,7-Tetrahydrobenzo[C]thio- phene (4,5,6,7-tetrahydroisothianaphthalene). . 54 Preparation of Acetylene Dicarboxylic Acid. . . 55 Preparation of Dimethyl Acetylenedicarboxylate. 55 Preparation of Dinitroacetylene . . . . . . . . 55 Preparation of Nitryl Chloride (Nitroxyl chloride) . . . . . . . . . . . . . . . . . . . 56 Preparation of Dinitroacetylene . . . . . . . . 56 Preparation of Tetracyanoethylene . . . . . . . 58 Cyanoacetamide I. . . . . . . . . . . . . . . . 58 Malononitrile II. . . . . . . . . . . . . . . . 59 vi TABLE OF CONTENTS - Continued Page Dibromomalononitrile-potassium bromide Complex 59 III [Br2C(CN)2]4KBr. . . . . . . . . . . . . . . 59 Tetracyanoethylene IV. . . . . . . . . . . . . . 59 The Reaction of Dinitroacetylene with Thi0phene. 6O Attempted Preparation of Dimethyl 7-thiabicyclo- [2.2.1]heptadiene(2,5)dicarboxylate(2,5) . . . . 62 Attempted Preparation of 7-Thiabicyclo[2.2.1]- heptadiene(2,5)dicarboxylic(2,5)acid . . . . . . 65 Attempted Preparation of 7-Thiabicyclo[2.2.1]- heptene-S-dicarboxy(2,5)anhydride. . . . . . . . 64 Attempted Preparation of 2-Cyano-7—thiabicyclo- [2.2.1]heptene . . . . . . . . . . . . . . . . . 65 The Reaction of Tetracyanoethylene with Thio— phene. . . . . . . . . . . . . . . . . . . . . . 66 The Second Attempt to React Tetracyanoethylene with Thiophene . . . . . . . . . . . . . . . . . 67 A Third Attempt to React Tetracyanoethylene with Thi0phene. . . . . . . . . . . . . . . . . . . . 69 A Fourth Attempt to React Tetracyanoethylene with Thi0phene . . . . . . . . . . . . . . . . . 69 The Fifth Attempt to React Tetracyanoethylene with Thi0phene . . . . . . . . . . . . . . . . . 70 The Attempted Preparation of 1,2,5,4-Tetrahydro— 5,6-dimethoxy-1,4-endothi0phthalic anhydride(2,5) 70 The Attempted Preparation of 2,2,5,5-Tetracyano- 5,6-dimethoxy-1,4—dihydro-1,4-endothiobenzene. . 71 The Attempted Preparation of 1,2,5,4-Tetrahydro- 5,6-dimethyl-1,4-endothiophtha1ic anhydride(2,5) 75 The Attempted Preparation of 2,2,5,5-Tetracyano- 1,4-dihydro-5,6-dimethyl-1,4-endothiobenzene . . 74 vii TABLE OF CONTENTS - Continued Page The Attempted Preparation of 1,2,5,4-Tetrahydro- 5,6-diphenyl—1,4-endothiophthalic anhydride(2,5) 75 The Attempted Preparation of 2,2,5,5—Tetracyano 5,6-diphenyl-1,4-dihydro-1,4-endothiobenzene . . 76 The Preparation of 5,6,7,8-Dibenzo-1,2,5,4- tetrahydro-l,4-endothionaphthalene(2,5)anhydride by the Reaction of 4,5,6,7-Dibenzoisothionaph- thalene with Maleic Anhydride. . . . . . . . . . 78 The Preparation of 1,2,5,4,5,6,7,8-Octahydro—1,4- endothionaphthalene(2,5)anhydride by the Reaction of 4,5,6,7-Tetrahydrobenzo[CJthiophene with Maleic Anhydride . . . . . . . . . . . . . . . . 80 The Preparation of 5,6,7,8-Dibenzo-2,2,5,5-tetra— cyano-1,4-dihydro-1,4-endothionaphthalene by the Reaction of 4,5,6,7—Dibenzoisothionaphtha- lene with Tetracyanoethylene . . . . . . . . . . 81 The Preparation of 1,4,5,6,7,8—Hexahydro-2,2,5,5- tetracyano-i, 4- -endothionaphthalene by the Reac- tion of 4, 5, 6, 7-Tetrahydrobenzo[CJthiophene with Tetracyanoethylene . . . . . . . . . . . . . . 85 The Attempt to Prepare 1, 4-Dihydro- -L 4— endothio- naphthalene (The Reaction of Thi0phene with Benzyne) I . . . . . . . . . . . . . . . . . . . 84 Second Reaction of Thi0phene with Benzyne. . . . 86 The Third Attempt to Prepare 1,4-Dihydro—1,4- endothionaphthalene. . . . . . . . . . . . . . . 91 ~The Reaction of 5,4-Dimethylthi0phene with "Benzyne" in an Attempt to Prepare 2,5-Dimethyl- 1,4-dihydro-1,4-endothionaphthalene. . . . . . . 98 The Reaction of 5,4—Dimethoxythiophene with "Benzyne" in an Attempt to Prepare 2,5-Dimethoxy- 1,4-dihydro-1,4-endothionaphthalene. . . . . . . 104 The Reaction of 5, 4-Diphenylthi0phene with "Benzyne" in an Attempt to Prepare 2, 5-Diphenyl- 1, 4-dihydro-1, 4-endothionaphthalene. . . . . . 109 viii TABLE OF CONTENTS - Continued Page The Preparation of 6,7,8,9-Dibenzo-5,10—dihydro- 5,10-endothioanthracene by the Reaction of 4,5,6,7-Dibenzoisothionaphthalene with "Benzyne" 112 Preparation of 5,6,7,8,9,10-Hexahydro-9,10-endo— thionaphthalene by the Reaction of 4,5,6,7- Tetrahydrobenzo[C]thi0phene with "Benzyne" . . . 116 Reaction of Methanolic Hydrochloric Acid with 5,6,7,8,9,10-Hexahydro-9,10-endothioanthracene . 118 Reaction of 5,6,7,8,9,10-Hexahydro-9,10-endo— thioanthracene with Sodium Hydroxide . . . . . . 118 SUMMARY . . . . . . . . . . . . . . . . . . . . . . . 120 BIBLIOGRAPHY. . . . . . . . . . . . . . . . . . . . . 122 APPENDIX. . . . . . . . . . . . . . . . . . . . . . . 128 Experimental . . . . . . . . . . . . . . . . . . 128 Infrared Spectra . . . . . . . . . . . . . . . . 159 ix LIST OF FIGURES FIGURE I. 4—Chlorocyclohexene oxide. . . . . . . . . . . II. 5,6,7,8-Dibenzo-1,2,5,4-tetrahydro-1,4—endo- thionaphthalene(2,5)anhydride. . . . . . . . . III. L 2, 5, 4, 5, 6, 7, 8- -Octahydro-1, 4- -endothionaph- thalene(2, 5)anhydride. . . . . . . . . . . . . IV. 5,6,7,8-Dibenzo-2,2,5,5—tetracyano-1,4-dihydro- 1,4-endothionaphthalene. . . . . . . . . . . . V..1,4,5,6,7,8—Hexahydro-2,2,5,5-tetracyano—1,4- endothionaphthalene. . . . . . . . . . . . . . VI. 1,4-Dihydro-1,4-endothionaphthalene. . . . . . VII. 6, 7, 8, 9-Dibenzo-5,10——dihydro-—5,10-endothio- anthracene . . . . . . . . . . . . . . . . . VIII. 5,6,7,8,9,10-Hexahydro—9,10-endothioanthracene IX. 5-Phenylthiophene. . . . . . . . . . . . . . . X. 2-Phenylthiophene. . . . . . . . . . . . . . . XI. 2,4-Dinitrophenyl-1-naphthylthioether. . . . . XII. 2,4-Diphenylthi0phene. . . . . . . . . . . . . XIII. 2,5-Diphenylthiophene. . . . . . . . . . . . . XIV. 5,4-Diphenylthi0phene. . . . . . . . . . . . . ‘XV. 2,5-Dipheny1thiophene. . . . . . . . . . . . . XVI. 4,5,6,7-Dibenzoisothionaphthalene. . . . . . . XVII. 4,5,6,7-Tetrahydrobenzo[C]thiophene. . . . . . Page 159 140 141 142 144 145 146 147 148 149 150 151 152 155 154 ,155 INTRODUCTION The present investigation was undertaken with the dual objectives of develOping synthetic procedures to obtain bicyclic sulfur compounds, wherein the sulfur atom bridges a six membered ring at the 1,4-positions, and to investigate their chemical and physical properties. The parent structure of compounds of this general type is 7-thiabicyclo[2.2.1]heptane. Its synthesis has been reported by the late Dr. Birch and his collaborators working at the British Petroleum Institute (1). Interest in these types of bicyclic sulfur compounds was concerned with the effects of the sulfur atom on the reactivity of the bicyclo system under conditions which could give rise to a carbonium ion type of rearrangement, either classical or non—classical as in the non-hetero system, norborane s X \ \ ”RX :3: or cause the sulfur bridge to Open by hydrolysis, oxidation or other chemical reactions. It was anticipated that an investigation of the re— actions of thiobicyclic compounds would permit a determina- tion of whether their physical and chemical properties are related to d orbital overlap of the sulfur atom and/or its participation effects in the total properties of such com- pounds. To experimentally study the reactions of a thio-bicyclic compound, it should have some functional grOUp or reactive center present in its structure, e.g., unsaturation or a functional group. The reactive center should be of such a nature as to promote the formation of an ion while the func~ tional group should help elucidate the structure of the products of its reactions, and help account for any struc- tural rearrangements occurring during its reaction. ~A structure permitting an experimental approach to this problem-would be a substituted 7-thiobicyclo[2.2.1]heptane, namely, 1-hydroxy-7-thiobicyclo[2.2.1]heptane ’. 0H The presence of the hydroxyl group could be utilized to introduce a double bond into the thiobicyclo structure through the Chugaev reaction, or a simple xanthate decomposition. An alternate approach to obtaining a reactive bicylic sulfur compound seemed possible through the Diels-Alder re_ action. ‘With the renewed interest in this reaction due to the development of newer and very reactive dienOphiles, such as benzyne, tetracyanoethylene, dicyanoethylene and perfluoro~ butyne (2), it was anticipated that thiophene or some of the 5,4-disubstituted derivatives might be made to undergo the Diels-Alder type reaction and yield the thio-bicyclo type compounds, S R; R3R4 R2 R5 5 R1=R2=H, CH3-, CH30-, E::]_ R3=R4=R5=R5= -CN or R‘ pm R‘“ R2 R4 ' R3'=R4'= ‘CN, -N02, -CF3 or S R. " R2 Other possible experimental approaches suitable to obtaining the desired thio-bicyclo compounds would be the Dickman condensation of a dicarboxydihydrothiophene S S CHgCOZH COgH 1)Ketone ’ ——> reduction ’. COgH . 2)Decarboxy-a lation O Furan and its derivatives readily undergo a Diels—Alder reaction. The treatment of such adducts with thiourea or thiocyanate ion might be utilized to exchange the oxygen by sulfur in reactions similar to those reported by Van Tamlen SCN O + KSCN -—>- ; ‘ —fi> S + OK KOCN (2) and extended to O HISTORICAL Several references to thiobicyclo compounds, endothio— bridge or epithiobridge, have appeared in the chemical literature. Birch and co-workers (1) isolated and characterized, 7—thiobicyclo[2.2.1]heptane S ’ from eastern Mediterranean crude oils and in further research were able to synthesize this compound in a series of re— actions starting with cyclohexane[1,4]diol. OH OH c1 \~ CH E SH §——). ' >= 3 s» -HgO OH c1 c1 fi fi S-C-CH3 S-C-CHa + C1 C1 I II S S KOH/CH3CH20H44 ‘ + I and II Reflux ’2 I' II' A Herzfelder in 1895 reported the synthesis of 1,4— thianaphthene[1,4—Epithionaphthalene] by pyrolyzing a mixture of 1-nitronaphthalene and sulfur (5). He assigned this materi— 013 Hartough and Meisel (4) proposed that such a structure al the endo structure even if initially formed would be very unstable due to the presence of double bonds at the bridgehead carbon atoms, and that these would be readily Opened by an attack of a second sulfur atom to yield the following compounds, «D -> ' CM 31‘} S At present the existence of the proposed endothiobridged compound has not been substantiated by synthesis or proof of structure. A compound, 9-phenyl-9,10-dihydro-thio-9,10-anthracene having an epithiobridge O .// \ #0 H was reported by Bistrzycki and Brenken (5). Dufrasisse and Daniel (6) in 1957 demonstrated that the structure of this compound was actually 1,5-diphenylisothionaphthalene. C? 0 They also observed that 1,5-diphenylisothionaphthalene failed S to undergo a Diels—Alder reaction with maleic anhydride as did its oxygen analog,.1,5-diphenylisobenzofuran. In 1959, Clapp (7) reported the reaction of dinaphthy- lene-thi0phene with maleic anhydride. However the Diels- Alder adduct was never isolated due to the drastic, experi- mental conditions required to bring about the reaction. The structure of the product could only be eXplained by assuming that a Diels-Alder reaction had occurred in which the adduct loses hydrogen sulfide to form the dinaphthylene phthalic anhydride A very reasonable basis for the formation of such a product is that once the epithiobridge was formed the driving force or resonance energy gain resulting from the loss of hydrogen sulfide lead to the formation of a "new" benzene ring. Clapp found in the same investigation that thionessal would not undergo a Diels—Alder reaction with maleic anhydride. In.1945, Allen and Gates (8) in their studies of the reactivity of complex thiophene derivatives reported the formation of a compound having an epithiobridge by reacting 1,5,5,6-tetraphenylisothionaphthalene with maleic anhydride. They isolated an adduct and found that it lost hydrogen sulfide when refluxed with alcoholic hydrogen chloride. HCl ROH Reflux The postulated reason for the reaction of the substi— tuted isothionaphthalene with maleic anhydride is the locali- zation Of the double bonds in the "thiophene" ring. It has lost its aromatic characteristics. Once the thiobridge is formed, it is very reactive and by refluxing in alcoholic hydrogen chloride the bridge sulfur is Opened. The additional 10 driving force Of this reaction can be due to the formation of the "new” aromatic ring A. The reason for the tetraphenyl derivative reacting while the 1,5-diphenylderivative failed to react under Diels-Alder conditions (6) could be rational- ized as due to a decrease in the resonance energy of ring B in the starting material caused by the 5,6-diphenyl grOUps and by the formation of the new aromatic ring in the tetra- phenyl derivative whereas the 1,5-diphenylisothionaphthalene does not have these substituents on ring B to help decrease its resonance energy. Thus, these investigations all report that attempts to employ thiophenecn:isothionaphthalene(benzo[C]thiophene) in the Diels-Alder synthesis fail unless the thiophene derivative is highly substituted and that where adducts are formed the sulfur bridge is easily eliminated as hydrogen sulfide, usually during the reaction. In 1954, Dann and co-workers (9,10,11) reported the reactions of substituted isothionaphthalenes with maleic anhydride to form endothiobridged compounds. The adducts were isolated and their chemical properties studied. .Hs , H3 H\_ ‘90 CH3 3 CH3 AP / C ---C\ C S +- H o .__> liilmmllfilll \O \\ /C-—-C<; CH3 é/ CH3 CH3 H 0 H3 \\ 0 CH3 CH3 //0 y usion \\ CH3 CH3 0 11 Recently two additional thiophene derivatives have been reported in the literature and both were found to undergo a Diels-Alder reaction with reactive dienophiles. Meyer and co-workers (12) reported a study of the synthesis Of isothio— naphthalene(benzo[CJthiOphene) and its chemical properties. It undergoes a Diels—Alder reaction with maleic anhydride to form a 1,4-endothiobridged bicyclo compound. H\C _f ' C //\\S \ \\ C“ —d<() i c//0 \ \O O O Cava and Van Meter (15) in 1962 reported the synthesis of 1,5-diphenyl[5,6]benzoisothionaphthalene. This material was found to react with tetracyanoethylene to form a stable Diels-Alder adduct. The isothioanthracene did not react with maleic anhydride or n—phenylmaleamide to yield an adduct. // s + (NC)2C=C(CN)2‘—>' \\ O m.p. 268-280 c O O m.p. 198-202 C Complete literature references and reviews on the Diels- Alder reaction (14-28) are far too numerous to cite all Of them. Thus only general references concerning this reaction are given in the bibliography unless a particular article 12 had some special relevance to the present investigation. The literature references (14-28) report on numerous aSpects, such as mechanisms and kinetics, of the Diels-Alder reaction and on the great variety of dienes and dienophiles that have been employed in this very general reaction. .Diels auui others (27,28,29) have reported the failure of a Diels—Alder reaction to occur between thiOphene and its "simple" derivatives with maleic anhydride and other "low reactive" dienophiles. Thi0phene derivatives as well as benzene derivatives show a tendency to react with dienOphiles only if their de- rivatives are very complex, as was previously discussed, that is, substituted with benzo[C]thiOphene(isothionaphthalene) or when the dienophile is extremely reactive as described for benzene reacting with perfluorobytyne (29). The initially formed adduct, 5,6-bis(trifluoromethylbicyclo[2.2.2]octatriene was not isolated because it reacted with a second mole of the reactive perfluorobutyne and then rearranged to yield F3C C CF3 F3C CF3 2,5,6,7 tetrakis(trifluoromethyl)naphthalene. 15 With the advent of new reactive dienophiles such as "benzyne" (50-42), Tetracyanoethylene (45,44) and perfluoro— butyne (29) and a renewed interest in dicyanoacetylyene (45,46,48), it was anticipated that perhaps one or more Of these dienophiles would react with thiophene or one Of its 5,4-disubstituted derivatives to provide a simple direct synthetic route to the endothiobridged bicyclo compounds. Of the reactive dienophiles, tetracyanoethylene and benzyne have been studied more extensively and as they were also readily available, these were utilized in attempts to synthesize the sulfur bridged compounds. It has been reported that benzyne reacts with furan (55) to give an endo-oxo bridged compound O a“ in good yield (46%). N-methyl pyrole likewise was found to react with benzyne (58) but the simple adduct was not isolated as it reacted with a second mole of benzyne followed by rear- rangement of the product to give 14 Anthracene has been reported to react with benzyne to yield triptycene (55,57), while cyclopentadiene reacted with the same reagent to give endomethylene[1,4]dihydronaphthalene ’1 Because of this reactivity of benzyne and other examples of similar reactivity reported by Wittig, it was anticipated that benzyne would react with thiOphene or one of its derivatives, whose aromaticity had been "reduced" by substitution, in the 5,4-position, to give the desired simple bicyclic sulfur bridged structure through a Diels—Alder reaction. Further, it was also anticipated that tetracyanoethylene because of its reactivity with dienes (47) would also yield an adduct with thiOphene or one of the 5,4-disubstituted thiOphenes. DISCUSSION In order to study the reactivity of the sulfur atom in an endothiobicyclo compound, these compounds must first be Obtained. The simplest member of the series, 7-thiobicyclo- [2.2.1]heptane was synthesized by Birch and co—workers (1). Its structure contained no other functional grOUp besides the sulfur atom and for the purposes of investigating reac- tions taking place, such as ring Openings and rearrangements, it was necessary to have some other functional group on the molecule. .Following the procedures of Birch (1), 4—chlorocyclo— hexene was prepared as an intermediate in the attempted preparation of 2-hydroxy-7-thiobicyclo[2.2.1]heptane. The 4-chlorocyclohexene was converted to 4—chlorocyclohexene oxide by peracetic acid (49,50). This is the first reported preparation Of 4—chlorocyclohexene oxide. There appeared to be two fractions of material which had almost identical infrared spectra but differed in their boiling point. In a later communication, Taft (51) reported the preparation of 4-chlorocyclohexene oxide using p—nitrOperbenzoic acid and apparently obtained only one compound. This compound's infrared spectrum, boiling point and refractive index agreed 15 16 with a composite fraction of the material obtained in this study. An infrared spectrum of the latter material is shown in Figure I. -The 4—chlorocyclohexene oxide on reaction with thioacetic acid yielded more than the two expected products; 4-chloro-2- hydroxycyclohexane-1-thioacetate and 5-chloro-2-hydroxycyclo~ hexane-l-thioacetate. o [I S-C-CHs OH O ' | (Bl OH S 'é-CH3 + CH3 -C "SH —_>' + C1 C1 Gas-liquid chromatographic analyses of the reaction pro- Cl ducts indicated that five compounds were present. .Attempts to separate these by liquid chromatographic methods yielded only three fractions. Several attempts were made to separate and identify the five products. It was originally believed that the 4—chlorocyclohexene oxide was obtained as cis-trans isomers. C1 C1 These isomers, on reaction with the thioacetic acid, would yield four possible products. The fifth product was believed to be 4-chlorocyclohexane—1,2-diol. 17 Following communication from Taft (51) it was found that the previous distillation of the 4-chlorocyclohexene oxide had been in error. Therefore the five products could not be explained by cis-trans isomers. There have been references in the literature (55) on transesterification of thioacetates when adjacent to hydroxyl groups. The five products can thus be explained by the following reaction scheme. 0 CH3 -g-SH4 c-caa OH |o| OH S-C-CH3 OH + 1 Cl 1 I I, o-d-cas ‘0 O-Cl-CH3 . SH 1 c1 NO analytical proof of the above compounds could be obtained except a series of infrared spectra and sulfur analysis. Attempts were made to carry out an ester analysis of the reaction products but these gave very erratic results. The reaction product from the reaction of 4-chlorocyclo- hexene oxide and thioacetic acid, on being set aside over night, became a viscous brownish Oil. In a further attempt to prepare the 2-hydroxy-7-thiabicy- clo[2.2.1]heptane, a freshly prepared reaction product of 4-chlorocyclohexene oxide and thioacetec acid was added to a 18 refluxing ethanolic potassium hydroxide solution, which would, as reported by Birch (1), close the bridged "sulfur atom." The only product obtained by this procedure was an unidentifiable tar. The next approach tried in attempts to prepare the bridged sulfur compound was that of Herzfelder (5) reported in 1895 for the syntheses of 1,4—thionaphthalene(1,4-epithio— naphthalene). He reacted 1-nitronaphthalene with sulfur and by adding selective solvent admixtures to the reaction mixture precipitated an amorphous material (m.p. 1550) which he assigned the structure: 013 On repeating Herzfelder's procedures, no solid with a melting point of 1550 could be isolated. Making use of all known product isolation techniques, such as liquid chroma- tography, vacuum distillation, etc., the attempts to isolate the epithionaphthalene were unsuccessful. All of the com- pounds which were obtained had sulfur analyses greater than 50 per cent while the theoretical sulfur content of epithio— naphthalene is 20.2 per cent. With the failure to isolate an endothiobicyclo—ring structure by the previous two methods, and the advent Of the new very reactive dienophiles, tetracyanoethylene and "benzyne," the next approach was through the Diels-Alder 19 reaction. It was anticipated that thiOphene or one of its 5,4-disubstituted derivatives could be caused to undergo the (Diels-Alder reaction and thereby yield the endothio- bicyclo compound. For this study, a series of 5,4-disubstituted thiophenes were required as intermediates. Thus, 5,4-dimethylthiophene (52), 5,4-diphenylthi0phene (52), 5,4-dimethoxythiophene (70,75,74), 4,5,6,7—dibenzoisothionaphthalene (9) and 4,5,6,7- tetrahydrobenzo[C]thiophene were prepared by the method of Hinsberg (52). The 5,4—disubstituted thiophenes and thiophene were .allowed to interact with various dienophiles, such as tetra- cyanoethylene, "benzyne" and maleic anhydride, and the materials isolated from the reactions were analyzed for pos- sible Diels-Alder type reactions. The first in the series of these reactions was the re- evaluation Of the reactivity Of thiophene and some of the "common" dienophiles in attempts to Obtain the Diels—Alder adduct. Thiophene was mixed with a dienophile; acrylonitrile, .acrylic acid, methyl acrylate, dimethyl acetylenedicarboxylate, acetylenedicarboxylic acid, or maleic anhydride in tetra- hydrofuran. The reaction conditions were at ambient tempera— ture or at the reflux temperature of the solvent. (As had previously been reported by Alder (21,24) and others (18) no evidence of a reaction could be ascertained. 20 The 5,4-disubstituted thiophenes, 5,4-diphenyl-, 5,4-dimethyl—, and 5,4-dimethoxythiophene, were similarly treated with maleic anhydride in a tetrahydrofuran solvent and again no evidence Of a Diels-Alder reaction could be ascertained. In each case only starting materials were recovered. The last two 5,4-disubstituted thiophenes, 4,5,6,7-tetra— hydrobenzo[C]thiOphene and 4,5,6,7-dibenzoisothionaphthalene, were allowed to interact with maleic anhydride and in each of the latter cases a product was Obtained and identified. These compounds are 5,6,7,8-dibenzo-1,2,5,4-tetrahydrO-1,4— endothionaphthalene(2,5)anhydride (9), O c C!) \ /o c D \ o and 1,2,5,4,5,6,7,8-octahydro-1,4—endothionaphthalene(2,5)- .¢O \ anhydride: 0 1 C” U" \ O /’ C t. 0 Their infrared spectra were obtained and are Figures II and III respectively. Both Of these compounds were refluxed with methanolic hydrogen chloride. In the case of the dibenzotetrahydro 21 endothionaphthalic anhydride, no reaction occurred and only starting material was recovered. With the octahydroendo- thionaphthalic anhydride, a reaction did occur as evidenced by the evolution of hydrogen sulfide. The product, isolated from the reaction of octahydroendothionaphthalic anhydride with alcoholic hydrogen chloride, melted 1500 higher than the starting material and qualitative sulfur tests indicated the absence of sulfur in the product. The most probable structure for this product is tetrahydronaphthalic(2,5) acid. .The test with methanolic hydrogen chloride has been used by Dann and co-workers (9,10,11), Birch (1) and Allen and Gates (8) for Opening the 1,4—endothiobridge. Wittig and co-workers (54,55,56,58) also used the same method to open the 1,4-Oxobridge compounds. The above difference in the reactivity of the two endo— thiobridged compounds may be explained as due to the differ- ence of resonance energy gained on loss of the thiobridge. For the complex dibenzotetrahydroeqdothionaphthalic anhydride, the gain in resonance energy of the whole molecule on the loss of the sulfur atom is of the order of one or two kilo~ calories. For the simpler octahydroendothionaphthalic anhydride, the gain in resonance energy is of the order of 50 to 55 kilocalories. Therefore the octahydroendothionaph- thalic anhydride would convert to the tetrahydrophthalic acid or anhydride because of the driving force of this gain in resonance energy . 22 A sodium hydroxide fusion of each of these compounds led to the loss of the sulfur bridge and the eXpected products were Obtained. The dibenzotetrahydroendothionaph— thalic anhydride gave 5,6,7,8-dibenzonaphthalic anhydride, which was identified by its melting point and elemental analysis in agreement with the literature values (9) for this material. The product from octahydroendothionaphthalic anhydride fusion with sodium hydroxide was tentatively identified by its elemental analysis and the Observation that the melting point of this product was identical to the melting point of the product Obtained from the methanolic hydrogen chloride reaction. The above endothiobridge compounds were set aside for further study and another series of reactions was initiated with tetracyanoethylene and thiophene and its 5,4-disubsti- tuted derivatives. Tetracyanoethylene appeared to react with thiophene, 5,4-diphenylthiOphene, 5,4-dimethylthiophene or 5,4-dimethoxy— thiophene, but on the application of isolation procedures to the reaction products the only isolatable materials were the. starting materials and some tarry residues. The remaining ‘5,4-disubstituted thiophenes, 5,6,7,8-dibenzoisothionaph- thalene and 4,5,6,7-tetrahydroisothionaphthalene, were caused to react with tetracyanoethylene and both compounds gave a reaction product. 25 The 5,6,7,8-dibenzo-2,2,5,5-tetracyano-1,4—dihydro-1,4- endothionaphthalene appears to be a very stable compound at ambient conditions. .After tentative identification of the product by elemental analysis, the product was set aside for further study. The 1,2,5,6,7,8-hexahydro-2,2,5,5rtetracyano—1,4-endo— thionaphthalene was also isolated and identified by elemental analysis. However, it decomposed when kept at room temperature for two weeks. It appeared to be stable for three months at —40°. This material was set aside also for further study. .None of the previous attempts to prepare the endothio- bicyclo compounds gave a simple bridged molecule of reason- ably good stability. Therefore the last series of reactions investigated started with thiophene and the 5,4-disubstituted thiOphenes reacting with "benzyne,“ in attempts to prepare the endothiobicyclo bridge compounds. 24 The first synthesis attempt in this series was the reaction of thiophene with'benzyne. The materials isolated from this reaction indicated that benzyne had reacted with the thiOphene in a very complex reaction. During the course Of repeating the preparation it became evident that the following influenced the reaction, and type of product Obtained; (1) the type of solvent used, (2) the presence of moisture, (5) the amount of oxygen in theJnitrogen atmosphere, and (4) reaction temperature. A gas chromatographic analysis of the reaction products indicated that some twenty compounds could be present. The separation and identification of these proved to be extremely difficult if not impossible. By liquid chromatographic techniques several products were isolated and identified as: 2-phenylthiOphene (15%), naphthalene (10%), 5-phenylthiophene (5%), triphenylene (5-16%). By liquid chromatographic treatment of the vacuum distillation distillate, 2,5—diphenylthiophene (1%), 5,4- diphenylthioPhene (1%), 2,5-dipheny1thiOphene (2%), 2-4- diphenylthIOphene (1%), and many other solids and oils some of which contained sulfur, were isolated. One Of the fractions obtained from the vacuum distilla- tion was a crystalline solid which melted in the range 78.50-80.00. The infrared spectrum Of this compound was completely different from that of naphthalene and qualitative tests indicated the presence of sulfur. On Obtaining its elemental analysis, it was found to have an empirical formula, 25 .CloHes. It was believed that this compound was the expected V1,4-dihydro-1,4—endothionaphthalene OI . The infrared spectrum was Obtained, Figure VI. Upon reacting the 1,4-dihydro-1,4-endothionaphthalene with alcoholic-hydrogen chloride, the endothio bridge was SH 4"“ HCl _44 CHaoH’" Opened similarly to the Opening of the oxo bridge found by Wittig and Pohmer (56) in the furan analogs. The product 1 or a-thionaphthalene was reacted with 2,4-dinitrochlorobenzene to give the expected thioether. SH c1 5 N02 N02 + N02 + Na 5 N02 The thioether was identified by elemental analysis, mixed melting point and comparison of its infrared spectrum with that of an authentic sample of the 2,4—dinitrOphenyl-1- naphthyl thioether. 26 A reasonable explanation for the number of products and their formation in the reaction of thiophene with benzyne follows. Recently Diels-Alder reactions with thiophene and its simple derivatives have been reported (12,15,54,55,56). Fields and Meyerson (55) pyrolyzed phthalic anhydride in the presence Of thiOphene at 6900. The major products were naphthalene, benzothiophene, 2- and 5-phenylthiophene and bithenyl. Naphthalene was the major product and its formation could best be explained by the benzyne formed on pyrolysis, since it is a strong dienophile, adding 1.4- rather than 1,2- to the thiOphene and at the high temperature this product v weoeso m —! decomposes to give naphthalene and sulfur. Fields and Meyerson (55) gave a mechanism for the formation of the products they Obtained. The 2- and 5-phenylthiophene resulted from hydrogen abstraction; benzyne abstracts a hydrogen on the thiophene ring. Arnett (40) demonstrated benzyne would abstract hydrogens in a series of experiments with aliphatic and unsaturated aliphatic compounds. When thiophene was sub— jected to the same pyrolytic conditions only trace amounts of naphthalene were isolated (55). Callander et al. (54) obtained a Diels-Alder adduct from the reaction of tetrafluorobenzyne with thiophene. This 27 adduct was very unstable and decomposed to give tetrafluoro- naphthalene F F F :._. F F F F F Finally Meyer et al. (12) and Cava et al (12,15) synthesized benzo[C]thiophene and found that it would readily undergo a Diels—Alder reaction with maleic anhydride (12,56) and N-phenylmaleimide (56). Therefore the products Obtained from the relatively mild benzyne thiophene reaction in this study could be explained as hydrogen abstraction by benzyne (40,41,55) from the thiophene to yield the phenylthiophenes. Arnett (40) and Simmons (41) found this to be the case in unsaturated aliphatic hydrocarbons and Fields et al (55) found evidence of this process in the pyrolysis of phthalic anhydride in thiophene. The explanation for the formation of naphthalene and the 1,4-dihydro-1,4-endothionaphthalene found in this study resulted from a Diels-Alder type reaction, which must be a 1,4-addition of the benzyne to the thiophene and because of the unstable nature of the adduct, it decomposed to give naphthalene 28 _ If the endothionaphthalene had undergone an inverse Diels-Alder reaction to yield acetylene and benzo[C]thiOphene-— Cava (56) and Meyer (12) reported that benzo[C]thiophene is very reactive--the benzo[C]thiOphene would have in turn reacted with another benzyne molecule to give a Diels-Alder adduct / I ' | ___,, S + H-CEC-H \\ which in turn could lose sulfur to yield anthracene. A solid believed to be anthracene in trace amounts was iso— lated from this reaction. The formation of benzo[C]thiophene was not favored by Fields (55), since the loss of a sulfur atom to yield naphthalene is energetically more favorable than the loss of acetylene to yield the less stable benzo[C]- thiophene. A solid melting from 184 to 1870 isolated from the reaction mixture was believed to be thionessal (tetraphenyl- thIOphene) but an infrared spectrum comparison, and the large mixed melting point depression (168°) with an authentic 29 sample prOved the solid was not thionessal. Wittig et al. (55-58) had isolated diphenylene (m.p. 112—1140) and tri— phenylene (m.p. 191-1940) from their benzyne reactions. Diphenylene was not isolated in any Of the reactions in this study but triphenylene was isolated. The benzo[C]thiophene found by Fields and Meyerson (55) in their reaction of benzyne with thiophene was not isolated in this study but could possibly be present in the Oily substance which contained sulfur and which had been separated by liquid chromatographic techniques. The following is a scheme of products that might be Obtained from the reaction of benzyne with thiOphenee-those unlined were isolated and identified in this study. .U_U._. .UW UmQO 1mm /|\.O_ 51 Considerable effort to isolate and identify the endo- thionaphthalene resulted in the identification of many of the reaction products but left many unidentified which did not contain sulfur. Several other methods were used in attempts to obtain further proof of identity of the 1,4—dihydro-1,4-endothio— naphthalene such as the phenylazide addition compound—- n-phenyltriazole--used by Alder and Stein (24,58,59). This method did not give an identifiable reaction product. In addition alkaline permanganate oxidation (5) gave phthalic anhydride, and bromination (5) gave 1,4-dibromonaphthalene. These last two positive tests helped to substantiate that the 1,4-dihydro-1,4-endothionaphthalene had been formed. Following procedures similar to those used for thio- phene; 5,4-dimethylthiOphene, 5,4-dimethoxythiophene and 5,4-diphenylthiophene were caused to react with benzyne. Gas chromatographic analysis of the reaction products indi- cated that in each case a reaction had taken place because of the 7 to 11 absorption peaks. Some of the products iso- lated from these reactions did have sulfur as a constituent but attempts to isolate the 1,4-dihydro—2,5-disubstituted- 1,4-endothionaphthalenes were unsuccessful. To gain some insight on the assumption that the large number of reaction products in the reaction mixtures might be due to benzyne reacting with itself or o-fluorobromobenzene or some intermediate reactive species, the following reaction 52 was undertaken. Using the same eXperimental procedures as were used with thiOphene, a benzyne reaction was conducted in the absence of thiOphene. Gas chromatographic analysis of this reaction product indicated three absorption peaks. Based on discussions of Wittig and Pohmer (55) and the physical prOperties of the three compounds isolated, they were tentatively identified as triphenylene (79%), biphenylene (6%) and 0,0'-dif1uorobiphenyl (6%). Thus this information and the fact that the triphenylene isolated from the reaction of benzyne with 5,4-disubstituted thiOphenes was only 6 to 10%2 indicates that thiOphene deriva— tives had reacted but the adducts had decomposed by the loss of sulfur or had reacted with another molecule of benzyne. The last two substituted thiophenes studied in this series of reactions, 5,6,7,8-dibenzoisothionaphthalene and 4,5,6,7-tetrahydroisothionaphthalene were caused to react with benzyne. Both of these thiophenes gave an identifiable reaction product. 6,7,8,9-Dibenzo—5,10-dihydro—5,10—endothioanthracene was tentatively identified by elemental analysis. Its infrared spectrum was obtained Figure VII. Attempts to 55 make a derivative involving the sulfur of the thiobridge by Opening the bridge with methanolic—hydrogen chloride, then reacting this product with 2,4-dinitrochlorobenzene were un- successful. During refluxing the adduct with the methanolic- hydrogen chloride the molecule lost hydrogen sulfide. The product isolated from the reaction appeared to be 6,7,8,9- dibenzo-5,10-dihydroanthracene by elemental analysis. 5,6,7,8,9,10—Hexahydro-9,10—endothioanthracene 0| )0 was tentatively identified by elemental analysis and appeared to be reasonably stable at ambient conditions. Its infrared spectrum was obtained Figure VIII. Attempts to prepare a derivative of the compound by Opening the endothiobridge with methanolic-hydrogen chloride and reacting the resultant product with 2,4-dinitrochlorobenzene were also unsuccessful N02 1' because the sulfur was lost as hydrogen sulfide during reflux- ing the adduct with the methanolic—hydrogen chloride. The product from this reaction was tentatively identified as 54 hexahydroanthracene by elemental analysis. The present study with the recent reports Of the Diels- Alder type reaction of thiophene (54,55) and its derivatives (12,15,56) yields either the stable adduct or the decomposi- tion products through loss of sulfur, indicates that even under the right conditions and with a very reactive dienophile, thiOphene does undergo a Diels-Alder reaction. Most of the work in this study was spent in attempts to isolate the endothiobridged compound and very little work was done on the identification of the other reaction products. Identification of these products might have unequivocally demonstrated that the Diels-Alder reaction was the principle reaction. The other reaction products probably are the decomposition products of the adduct. Callander, Coe and Tatlow (54) established that the very reactive tetrafluorobenzyne did react with thiophene at ambient conditions and the endothiobicyclobridged product from the reactive benzyne and thiophene was unstable and decomposed to yield tetrafluoronaphthalene F F H F __ F F ‘ IT» 0053 *3 F \=—— F F F H F I By liquid chromatographic techniques these investigators did isolate compound I whose n.m.r. was consistent with the 35 structure 5,6,7,8-tetraf1uoro-1,4-dihydro-1,4-endothionaph- thalene. The principle product was the tetrafluoronaphthalene and its formation could only be accounted for by a Diels-Alder type reaction. All evidence reported in the literature and the results obtained in the present investigation indicate that benzyne reacts with thiophene and its derivatives to yield Diels-Alder type adducts. These products in some cases are‘veryhunstable and decompose to yield naphthalene derivatives (54.55.56). Further work on isolating and identifying the various other reaction products especially those from benzyne with 5,4-dimethyl-5,4-dimethoxy- and 5,4-dipheny1-thiophene will be necessary to establish that the Diels-Alder reaction did take place. Further it will be necessary to determine what electromeric effects the 5,4—disubstituents had on the reactivity of the thiOphenes. Arnett (40) and Simmons (41) in their studies of benzyne were able to demonstrate that benzyne abstracts hydrogen and yields phenyl substitution in various aliphatic systems. This is the most rational basis based on current evidence to account for the formation of the phenylthiophenes found in the reaction product of benzyne with thiOphene. EXPERIMENTAL All melting points were corrected and were determined on a micro hot stage apparatus. Attempted Preparation of 1-Hydroxy-7—thiabicyclo- j2.2.1lheptane 717 ‘ép O OOH HCl ) \ \ A, -H20 ’ Na2C03 7 NaOMe . OH C1 C1 Cis-trans ' - C18 trans III I II 4" 9| 0 CH3 -C \ S-C-CHs OH 0 SH OH s-E—CHs _ > + Cl IV Cl S V OH SVI OH KOH vm —->.E.0H “ . " H20 Cl 56 37 Preparation of 4-Chlorocyclohexanol (II) 4-Chlorocyclohexanol, 1000 g.(6.64 moles), was prepared by the method of Owens and Robins (60) from 1,4-cyclohexanediol (I, Aldrich Chemical Co.) and concentrated hydrochloric acid in a 70-79% yield, b.p. 80-900/5 mm. Hg.(literature value b.p. 96-1060/10 mm. Hg., b.p. ao-asoc/s mm (60)) n20 1.4941 D (literature value n20 1.4947 (60)). D Preparation of 4-Chlorocyclohexene (III) 4-Chlorocyclohexene, 550 g~(5.00 moles), was prepared by the method of Owens and Robins (60) from 4-chlorocyclohexanol (II) and B-naphthyl sulfonic acid in a 59-45% yield, b.p. 88-93°C/150 mm. Hg., n20 1.4814 (literature values 51% yield, D b.p. 88-980c/14o mm. Hg. n20 1.4822 (60.1)). D Preparation of g-Chlorocyclohexene Oxide (IV) In a 500 m1., three necked, round bottom flask equipped with an adapter, a reflux condenser, thermometer, stirrer, and a dropping funnel was placed 20 g.(0.171 mole) of 4-chlorocyclohexene in 100 ml. of chloroform. To this solu- tion was added a mixture of 40 g.of 40% peracetic acid solu- tion [Becco Chemical Div., FMC., 16 g.peracetic neat, 0.21 mole, corresponding to a 25% excess over the stoichiometric amount required for the reaction] (49) and 9 g.(0.11 mole) of anhydrous sodium acetate as a buffering agent. The reaction 58 mixture was kept under constant stirring during a period of 2.5 hours while maintaining the reaction mixture temperature at 50. The reaction mixture was stirred for an additional hour, until samples taken from the reaction mixture indicate no further decrease in their peracetic acid content. The 4-chlorocyclohexene oxide was isolated from the re- action mixture by adjusting the pH to 7 with anhydrous sodium carbonate and separating the chloroform layer. The aqueous layer was extracted once with 25 ml.of chloroform. The chloroform was removed by distillation and the crude 4-chlorocyclohexene oxide obtained weighed 20 g.(0.15 mole, 88%). The crude 4-chlorocyclohexane oxide was fractionally distilled using an 18" helice packed column (50 x 1.5 cm, 5/16" Pyrex helices). Two fractions were obtained, 8 g. (0.06 mole) b.p. 128-1540/150 mm. Hg.and 7 g. (0.053 mole) b.p. 140-1500/150 mm. Hg. and approximately 5 g. of a polymeric residue remained. The refractive index of the two fractions was identical, n30 = 1.4915. An infrared spectra determined between salt plates on a Model 21 Perkin Elmer double beam instrument indicated the presence of the epoxide group with a strong absorption at 11.9 u (61) and a chloro substituent with absorption in 12-14 u regions. The two Spectra were almost identical and from all appearances the two fractions were identical. .It appeared that two isomers of the epoxide were obtained, the cis-trans isomers analogous to the diols. 59 The Second Pre aration of 4-Chlorocyclohexene oxide (IV) -oxabic clo[4.1.0]heptane) Using the method of Korach et al. (62) a second prepara- tion of 4-chlorocyclohexene oxide was undertaken. To a rapidly stirred suspension of anhydrous sodium carbonate (20 g., 0.18 mole) in a solution of 4-chlorocyclo- hexene (20 g., 0.17 mole) and 200 ml. of methylene chloride was added 55 g. of 40% peracetic acid solution (0.185 mole neat). The peracetic acid solution had been previously treated with 1 g. of anhydrous sodium acetate to neutralize the sulfuric acid present. The reaction temperature was maintained at 50 during 2.5 hours it required to add the peracetic acid solution. The reaction mixture was stirred an additional hour to complete the reaction. Titration of a filtered aliquot showed all peracetic acid had been consumed. The reaction mixture was filtered and the solid filter cake of sodium acetate, sodium bicarbonate and sodium carbonate was washed three times with 50 ml portions of methylene chloride. The majority of the methylene chloride was removed by distillation (Fenske column 50 x 1.5 cm.packed with 5/16" Pyrex helices). The residue in the distillation flask was then fractionally distilled in the same equipment. Again two fractions were obtained, 7 g.(0.055 mole) b.p. 129-1550/150 mm. Hg. and 7.2 g.(0.054 mole) b.p. 144-1510/150 mm. Hg. The infrared spectras of the two fractions were identical and in turn were found to be identical to the previously 40 prepared material. The refractive index, n30 1.4878 of the fractions was different. -A sample of the combined fraction of the 4—chlorocyclo— hexene oxide was submitted for elemental analysis. Anal. calc'd. for C3H9C10: C, 54.5; H, 6.8; Cl 26.8; Found: C, 54.28, 54.55; H, 6.68, 6.74; Cl, 26.69, 26.71 (51,65,64,65). The peracetic acid was assayed by adding 0.5 ml of the peracid solution to 1 g. of potassium iodide dissolved in 10 ml. of water containing 5-5 drOps of 5 N hydrochloric acid. The liberated iodine was titrated with 0.1 N sodium thiosulfate. A 1 ml. volume of the thiosulfate was equal to 0.008 g. of active oxygen or 0.076 g. of peracetic acid neat. The degree of reaction was followed by acidifying 1 ml. of the reaction mixture with hydrochloric acid, adding potassium iodide and titrating the liberated iodine with 0.1 N sodium thiosulfate solution. Reaction of 4-Chlorocyclohexene Oxide (IV) with Thioacetic Acid 1° s-A-CH3 0H 4,0 0H S-fi-CHg + CH3 -C ——>- + SH IV V VI 41 The procedure' of Birch, Dean and Hunter (1), utilized for the reaction of 4-chlorocyclohexene with thioacetic acid was followed. To 10 g.(0.075 mole) of 4-chlorocyclohexene oxide (IV) contained in a 250 m1., three necked, round bottom flask equipped with a reflux condenser, stirrer and dropping funnel, was added 8 g.of redistilled thioacetic acid (E.K. CO., b.p. 65-85.5°/742 mm., 0.105 mole, n30 1.4645). The reaction mixture was set aside in a hood for a day, to com- plete the reaction. Various methods were tried to determine the amount of unreacted oxirane remaining. The attempts were unsuccessful due to the presence of excess thioacetic acid. The excess thioacetic acid was removed by vacuum distillation, leaving a brownish colored viscous oily residue with a disagreeable odor. A sample of the residue was dis— solved in methylene chloride and a 5 u 1. portion ‘was in- jected into a F & M gas chromatograph with a 6 ft. G. E. silicone rubber column. The chromatogram had five peaks in addition to the initial methylene chloride peak. By estimat- ing the area under the peaks, an approximate measurement show a peak at 20 and 25 min., each 25%, a peak at 55 and 58 min., each 15%, and a single peak at 60 min., corresponding to 15%. A portion of the residue was subjected to vacuum distil- lation at 150 mm. Hg. However no distillate was obtained up to a temperature of 180°. The pressure was reduced to 0.5 mm. Hg. and a viscous material distilled at 124-1400 with 42 evidence of decomposition occurring. This material gave a negative sulfur test by sodium fusion with lead acetate method. The reaction described above was repeated with 4-chloro- cyclohexene oxide and thioacetic acid (1). The gas chroma- togram obtained had five major peaks and one minor peak. The brown oily residue was stored for further study. Attempted Preparation of 7—Thiobicyclo[2.2.1]heptanol OH The brown oily product (2.8 9.) obtained above was added dropwise to an alcoholic solution of potassium hydroxide (8 9.), ethanol (50 ml., 95%), and water (50 ml.), heated to its reflux temperature in a similar method to that used by Birch et al. (1). The reaction mixture was maintained at reflux for an.additional three hours to complete the reaction (1). It was then cooled to room temperature and extracted _with n-pentane. The pentane extracts were combined and shaken with a few iodine crystals, and then with a 10% potas- sium hydroxide solution to remove any free thiol present. The pentane extract was washed with water until neutral, .and dried over anhydrous sodium sulfate. The pentane was removed by distillation under reduced pressure to obtain a 45 polymeric material which gave a negative test for sulfur by the sodium fusion--lead acetate procedure. .Attempted Preparation of 1,4—Thionaphthalene by Herzfelders Method (5) 316 Following Herzfelder's procedure (5) 150 g. of 1—nitro- naphthalene (0.86 mole) was well mixed with 50 g. of flowers of sulfur (0.94 mole). The mixture was heated until an exo- thermic reaction commenced (500°C). The reaction was very vigorous as evidenced by foaming and evolution of sulfur dioxide and 1-nitronaphthalene vapors. After the reaction had ceased.and the mixture had cooled to room temperature, the greenish black solid was pulverized to a coarse tacky powder. It was boiled with ethanol (95%, 250 ml.) to remove unreacted 1—nitronaphthalene and sulfur. The dark green residue was then boiled (15 min.) with 10 ml. of chloroform and filtered. The filtrate wasdis- carded as it appeared to contain mainly unreacted sulfur. The second residue was boiled with a liter of chloroform, at its reflux temperature for two hours and filtered while hot. The chloroform extraction procedure was repeated three times. The terminal extraction was light green in color. The re- maining solid residue was set aside. 44 Following Herzfelders' procedure (5) the combined chloro- form extracts were concentrated under reduced pressure to a liter in volume and a green tacky amorphous solid was pre— cipitated by the addition of a liter of ethanol (95%). The green colored ethanol insoluble material was dissolved in a half liter of chloroform and the solution was heated to its boiling point and the green amorphous mass was again pre- cipitated by the addition of a half liter of ethanol (95%). This solution and reprecipitation procedure was repeated three additional times. The green amorphorus mass was again extracted by boiling with 100 ml. portions of ethanol (95%) until the extract was pale green in color. .This procedure yielded a dark green intractable mass whereas Herzfelder (5) reported an amorphous green powder (m.p. 1550). The tacky mass was insoluble in diethyl ether, methyl, ethyl and iso- propyl alcohol, hydrochloric acid (IN) and sodium hydroxide (IN) which were similar to the insolubilities of Herzfelder's solid. The tacky mass was soluble in chlorinated solvents, benzene, carbon disulfide and nitrobenzene. -Attempts to sublime or steam distill samples failed to effect any separa- tion or further purification. Prolonged heating at atmospheric or pressures as low as 0.005 mm. Hg. only resulted in decomposition as evidenced by the evolution of gasseous products and charring of the sample. Sulfur analysis of the tacky green product gave 52.1, 52.7% S (literature value 27% (5)). The calculated value for 45 sulfur for 1,4-thionaphthalene is 20.2%. Reacting samples of the green colored product with mercuric chloride, mercuric acetate or lead acetate failed to give a precipitate of organic sulfur compound. Some mercuric and lead sulfide was isolated from these test reaction products. A sample of the crude green product was refluxed with .alkaline potassium permanganate to obtain 5—nitrophthalic acid, m.p. 206-210O (mixed melting point with authentic sample gave no depression of the melting point). The yield of 5- nitrOphthalic acid obtained was 14%. Another sample of the green product was treated with fuming nitric acid (90%) under reflux, to obtain several products. Among these identified were the acids, 5-nitro- phthalic acid and phthalic acid. In addition several nitro aromatic compounds were iso- lated which contained no sulfur as determined by qualitative sulfur tests. A sample of the green product was treated with bromine in chloroform until an excess of bromine was obtained. The excess bromine and chloroform were removed by sweeping the solution with a nitrogen gas stream and the crude product obtained was compared to 1,4-dibromonaphthalene (m.p. 81-820C). The product from the bromination was an oil which could not be crystallized and thus was not the 1,4-dibromonaphthalene reported by Herzfelder. 46 Second Attempt to Prepare 1,4—Thionaphthalene The above experimental procedure (1) was repeated. After the evolution of gaseous products had ceased and re- action mixture had cooled to room temperature, it was boiled with seven separate half liter portions of chloroform, until no additional material could be extracted. The combined chloroform extracts were concentrated under vacuum to obtain 71 g. of a tacky greenish black powder. A 7 g. quantity of this material was dissolved in carbon tetrachloride and transferred to a alumina chromatographic column (1" x 16", A1203 activity Broch I). The column was eluted with carbon tetrachloride and three bands separated, each having 0.5 g. of material and a fourth band containing sulfur (1.4 g.). The three bands; two blue and one a reddish blue, gave negative tests for sulfur by sodium fusion and lead acetate. The column was eluted with cyclohexane (500 ml.) and developed a light blue band (0.7 g.) which gave a negative qualitative sulfur test. The column was then eluted with benzene and four bands were obtained; yellow, red, blue and green. The yellow band material (0.2 9.) had a melting point of 55-580C and was identified as 1-nitronaphthalene (by mixed melting point). The red band material (0.1 g) and blue band material (0.1 g.) each gave a positive qualitative test for sulfur. Infrared spectra were very complex and no identi- fication of these materials was possible. The green band material (2.0 9.) gave a positive test for sulfur. This 47 material had a melting point range of 45 to 680. Sulfur analysis gave 45% S [calculated for 1,4-thionaphthalene is 20.2%]. -Attempts to recrystallize this material failed to effect the melting point range. Elution of the column with diethyl ether and acetone yielded only trace quantities of a green amorphous solid. Elution of the column with chloro— form gave a yellowish colored band (1.1 g.). The material had a melting point range of 146 to 1520. Sulfur analysis was 22% S. A sample (0.1 g.) treated with nitric acid (90%) gave phthalic acid, benzoic acid and some nitro compounds. A sample treated with bromine in chloroform did not give the expected 1,4-dibromonaphthalene (m.p. 81-820). A sample of the yellow material was reflUxed in meth- anolic hydrochloric acid in attempts to open the 1,4-endo- thiobridge if it was present and obtain a-thionaphthalene. The solid obtained did not appear to have formed the expected 2,4-dinitr0phenylthio ether. “p 1 OOH? C“ CO ”a O” CO CO b.p. 259.3° (m.p. 176-176.5°c (69)) 48 The isolated solid had a melting point in the range 118—1220C. No evidence could be obtained which indicated that the re- ported 1,4-thionaphthalene had been prepared. The Preparation of 5,4-Disubstituted Thiophenes S x , x n n / \ OH-; I I X—C—C—X + H5C202C-CH2 CHZ‘COECZHS /\ H5C202C S COZCZHS + 1) H 2) A,Cuo,_co2 X X h (I or CuCrOX S /\ x = CH3-, , CH30-, Cl, etc. Preparation of Ethyl Thioglycolate (70,71) 2000 g. ethyl thioglycolate was prepared from thio- glycolic acid (E. K. Co, No. 2249) and ethanol following the procedure of Fawcett (70) adapted from the methods of Rischner and Speir (71). The yields of ethyl thioglycolate were 65 to 75% b.p. 52-540/11 mm. Hg. It had a refractive index of n30 = 1.4570 (literature value b.p. 156-1580/760 mm. n30 1.4568 (70)). 49 Preparation of Diethyl Thiodiglycolate (70) Diethyl thiodiglycolate, 1500 g. (18.5 moles) was pre— pared from the ethyl thioglycolate and ethyl chloroacetate by the procedure of Fawcett (70) and Overberger (72) in yields of 85 to 86%, b.p..105-1080/2 mm. Hg. It has a re- fractive index of n20 = 1.4644 (literature value b.p. 1050/ D 3 mm. Hg., 1150/5 mm., 1580/15 mm., n35 1.4619 (70,72)). Preparation of Disodium Salt of 2,5-Dicarbomethoxyr 5L4:dihydroxythi0phene (70,75) The disodium salt of 2,5-dicarbomethoxy-5,4-dihydroxy- thiOphene was prepared from diethyl thiodiglycolate and dimethyloxalate in absolute methanol.and sodium methoxide, by the procedure of Fawcett (70) which had been adapted from the method of Fager (75), in yields comparable to other investigators (70,75). Preparation of 5,4—Dimethoxy-2,5-dicarbomethoxy- thiophene (70,75,74) 5,4-Dimethoxy—2,5-dicarbomethoxythiophene, 70 g. (0.269 mole), was prepared from the disodium salt of 2,5-dicarbo— methoxy-5,4-dihydroxythi0phene and dimethyl sulfate by the best procedure found by Fawcett (70) in yields of 52 to 51%. These yields were less than those found by other investi— gators (70,75,74). 50 ,. -;.4* Preparation of5,4—Dimethoxythiophene (70,75,74) 5,4-Dimethoxythiophene, 40 g. (0.512 mole), was pre— pared from the 5,4-dimethoxy-2,5-dicarbomethoxythiophene by decarboxylation using guinoline and c0pper chrominum oxide catalyst prepared by the method of Connors, Folkers and Adkins (75) and by decarboxylation using quinoline and reprecipitated copper metal as described by Overberger's method (74). Both decarboxylations gave 5,4-dimethoxythio— phene in 44% to 60% yield, b.p. 106-1150/12 mm. Hg. (litera— ture value b.p. 1100/14 mm. Hg. (74) 108-1150/12 mm. Hg. (75)). Preparation of 5,4-Diphenyl-2,S-dicarboxythigphene HOgC s COgH 5,4-Diphenyl-2,5-dicarboxythiophene was prepared from diethylthiodiglycolate and benzil in absolute methanol containing sodium methoxide as the condensing agent by the procedures of Hinsberg (76) and Backer, Bulb and Stevens (77). These procedures in this laboratory yielded 265 g. (81% yield) of the 5,4-diphenyl-2,5-dicarboxythi0phene melting at 343° with decomposition (literature value 5410 (76,77)). 51 Preparation of 5,4—Diphenylthiophene (74,76,77,78) ls' 5,4-Diphenylthiophene, 60 g. (0.255 mole), was prepared from the 5,4-diphenyl-2,5-dicarboxythi0phene described above by decarboxylation using quinoline and copper powder following Overberger's method (74,78). The 5,4-diphenylthiophene was obtained in a 50% yield. Its melting point was 110-1120 (literature value 1140 (74,78)). Preparation of 5,4-Dimethyl-2,S—dicarboxy- thiophene (76,79) CH3 CH3 I) ll HOZC S C02H 5,4-Dimethyl-2,5-dicarboxythiophene, 500 g. (1.50 moles), was prepared from the diethyl thiodiglycolate prepared above and 2,5-butanedione (diacetyl, Aldrich Chemical Co.) in absolute methanol using sodium methoxide as the condensing agent by the procedures of Seka (79) and Hinsberg (76). The 5,4-dimethyl-2,5-dicarboxythi0phene was obtained in a 55% yield, and melted at 5250 with decomposition (literature value m.p. 527o decomp (79)). 52 Preparation of 5,4—Dimethylthi0phene 5,4-Dimethylthi0phene, 250 g. (2.25 moles) was prepared CH3 from the 5,4—dimethyl-2,5-dicarboxythi0phene described above by decarboxylation using quinoline and c0pper powder follow- ing Overberger's methods (72,78). 5,4-Dimethylthiophene was obtained in an 85% yield. It had a boiling point of 81-840/ 100 mm. Hg., and a refractive index of n25 = 1.5194 (litera- D ture value b.p. 145.5-146.5°/760 mm., n55 1.5187, n30 1.5212 (80)). Preparation of 4,5L6,7-Dibenzoisothianaphthalene-l,5- dicarboxylic Acid (76,9) 40.6 / \ S COgH 4,5,6,7-Dibenzoisothianaphthalene-1,5-dicarboxylic acid, 76 g. (0.256 mole) was prepared from diethylthiodiglyco- late and phenanthraquinone in absolute methanol using sodium methoxide as the condensing agent by the methods of Hinsberg (76) and Dann et al. (9). The dibenzo-dicarboxy-isothia- naphthalene was obtained in 76 to 88% yields. It melted at 255-2550 with decomposition (literature value m.p. 249-251O (d) (9,76). 55 Anal. Calc'd for c18H1004s: c, 67.07%; H, 3.12%; s, 9.94% Found: c, 67.00%; H, 3.56%; s, 9.20% (67,64). Preperation of 4,5,6,1:Pibenzoisothianaphthalene (9,76) 4,5,6,7-Dibenzoisothianaphthalene, 55 g. (0.255 mole), was prepared from the above preparation of 4,5,6,7-dibenzo- 1,5-dicarboxy-isothianaphthalene by decarboxylation using quinoline and copper powder following Overberger's methods (72,78). The 4,5,6,7-dibenzoisothianaphthalene was obtained in a 74% yield and its melting point was 165-1670 (literature value 166.5—167.0O (9)). (Anal..Calc'd for CleHloS: c, 82.01%; H, 4.30%; 3, 13.68% Found: c, 81.91%, 81.67%; H, 4.30%, 4.26%; 8, 13.85%, 15.67% (67). Preparation of 4 5 6 7-Tetrahydro-7 L5-dicarboxyr benzo[Clthiophene 76 Wtetramethylene 2, 5-dicarboxy- thiOphene) HOgC / \ C02H ' s 54 4,5,6,7-Tetrahydro-1,5-dicarboxybenzo[CJthiOphene, 40 g. (0.177 mole) was prepared from diethyl thiodiglycolate and 1,2-cyclohexandione (Aldrich Chemical Co.) in absolute methanol using sodium methoxide as the condensing agent by the methods of Hinsberg (76) and a more recent method reported by Meyer et al. (12). The tetrahydrodicarboxybenzo[C]thi0phene was obtained in 20 to 25% yields. It melted at 545-5440 with decomposition and sublimation (literature values 5410 (d)(76)). Anal. Calc'd for C8H10048: c, 53.09%; H, 4.46%; 8, 14.17% Found: c, 53.31%; H, 4.68, 4.41%; 3, 13.44, 13.37% (67) 13.96, 14.01, 14.06% (63). Preparation of 4L5L6,7-Tetrahydrobenzo[Clthiophene (4:5,6,7-tetrahydroisothianaphthalene) /\ $/ The 4,5,6,7-tetrahydrobenzo[C]thiophene, was prepared by the decarboxylation of the tetrahydro-dicarboxy-benzo[C]- thiOphene prepared above using quinoline and copper powder following Overberger's methods (72,78). 4,5,6,7-Tetrahydro- benzo[C]thiophene was obtained in 76-82% yields b.p. 88-900/ 11 mm. Hg., 215.20/740 mm. and its refractive index was n35 = 1.5632 (literature value b.p. 205—215°/760 mm. (76)). 55 (Anal. Calc'd for CeHioS: c, 69.51%; H, 7.29%; 8, 23.19% Found: c, 70.32%, H, 6.72%; 5, 22.75, 23.01, 23.21% (67,64). Preparation of Acetylene Dicarboxylic Acid Acetylene dicarboxylic acid was prepared by neutralizing the acid potassium salt of acetylene dicarboxylic acid (Aldrich Chemical Co.) with sulfuric acid using the method of Abbott et al. (81). The acetylene dicarboxylic acid was obtained in a 55% yield. It melted at.175—174.5o with de- composition (literature value m.p. 175—176O (d) (81)). Preparation of Dimethyl Acetylenedicarboxylate The dimethyl acetylenedicarboxylate, 60 g. (0.422 mole), was prepared by esterification of the acetylene dicarboxylic acid with methanol using the method of Stark et al. (82). Dimethyl acetylenedicarboxylate was obtained in a 66% yield. It boiled in the range 95-970/15 mm. Hg. (literature value b.p. 98°/20 mm. Hg. (82)). This compodnd is a very strong lachrymator and the lit— erature describes it as having vesicatory properties similar to that of all other esters of acetylene dicarboxylic acid. Preparation of Dinitroacetylene BngCEC-MgBr + N02Cl ——>’ OaN’CEC-NOZ 56 Preparation of Nitryl Chloride (Nitroxyl chloride (85)) Caution. The laboratory Operations were conducted in a well ventilated hood which was darkened to prevent the photochemical decomposition of the product. The procedure used to obtain nitryl chloride was that of Kaplan and Shechter (85). Fuming nitric acid was mixed with fuming sulfuric acid at 00. To the cold mixture at -80° was added chlorosulfonic acid (freshly distilled). As the chlorosulfonic acid was added dr0pwise the nitryl chloride was evolved and it was collected in a dry-ice cooled "trap". This particular preparation yielded 81 g. of nitryl chloride (literature value 95-100 g. 81—91% (85)). ,Preparation of Dinitroacetylene In a 2 1, three necked flask, equipped with a stirrer, reflux condenser fitted with a calcium chloride drying tube, and a drOpping funnel fitted with a calcium chloride drying tube was placed 27.1 g. (1.15 g. at) of Grignard grade magnesium turnings and 100 ml. of sodium dried diethyl ether. »A crystal of iodine was added to catalyse the reaction. To this mixture was added 5 ml. of ethyl bromide and the reaction was initiated by gently heating. The remaining ethyl bromide (70 ml. total 111.6 g., 1.025 mole) dissolved in 250 ml. of sodium dried ether was added during 2.5 hours to the reaction flask using the drOpping funnel at 57 a rate sufficient to maintain the reaction mixture at its reflux temperature. When the ethyl bromide had been added, the mixture was kept at its reflux temperature until the majority of the magnesium had reacted. The solution was filtered, to remove the few pieces of magnesium that remained, into a clean two liter flask. A liter of benzene, redistilled from phOSphorous penta- oxide, was added to the solution of the ethyl magnesium bromide in ether, and the majority of the ether was removed by distillation. The ethyl magnesium bromide-benzene solu- tion was cooled to 50 and while being vigorously stirred a rapid stream of acetylene was passed into it, using a fritted glass gas dispersing tube, for 5 hours. A pale yellowish- grey suspension was obtained. Considerable reaction heat was liberated-and external cooling by immersion of the reaction flask in an ice bath was necessary to control the reaction (84). To the above suspension was added 162 g. (2.00 mole) of nitryl chloride dissolved in 400 ml. of sodium dried diethyl ether during a 4 hour period. The temperature of the reaction mixture was difficult to maintain at 4°. During the addition of the nitryl chloride, the reaction temperature rose rapidly to 10-150. The addition of the nitryl chloride solution had to be interrupted and the reaction mixture had to be cooled again to 4°. These rapid temperature rises occurred 5-10 minutes after each addition of a portion of the nitryl chloride solution. 58 After 4 hours of reaction, as much ether as possible was removed with a water aSpirator concentrating the reaction mixture to approximately a liter. The solution was filtered through a medium fritted glass funnel to remove the pre- cipitated white solid and the solution was cooled to -50 at which temperature the solution started to crystalize. The dinitroacetylene solution (200 g., 2.5 moles) was stored in a dry-ice chest. It is extremely explosive at room tempera- ture and will explode when heated above 28°. Preparation of Tetracyanoethylene 0 H H NC-CHg-C-OC2H5 EEAQg—a' NC-CHg—C-NHg + c2H50H I I g§%5—>- CH2(CN)2 iii—5’ [Br2C(CN)2]4KBr POCIS II III 0 NE cs III 4934». \‘c=c’/ / \ NEC CEN IV Cyanoacetamide I The cyanoacetamide, 245 g. (2.92 moles), was prepared from ethyl cyanoacetate (Eastman Kodak Co.) and ammonium hydroxide by the method of Corson et al. (85). An 82% yield of the cyanoacetamide was obtained melting in the range of 118.5-119.5° (literature value, m.p. 119-120° (85)). 59 Malononitrile II The malononitrile, 84 g. (1.27 moles), was prepared from cyanoacetamide and phosphorous pentachloride by the method of Corson et al. (86). A 70% yield was obtained and melted in the range of 29-50.5O (literature value m.p. 28-500 (86)). Malononitrile can be vacuum distilled at 1150/50 mm. Dibromomalononitrileepotassium bromide Complex III [Br 2C (CN) 2] 4KBr Due to the irratating effect of this complex on the eyes and nose, the amount of material prepared in this synthesis was not determined. The dibromomalononitrile-potassium bromide complex was prepared from malononitrile, bromine and potassium bromide using the method of Carboni (87). The orange colored solid recovered from the reaction mixture liberates bromine on exposure to the air or on contact with hands or skin. This material must be handled with rubber gldVes in a good hood. The complex had to be kept thoroughly dry or the yield of tetracyanoethylene was low. Tetreeyanoethylene IV (CN)2C=C(CN)2 60 The tetracyanoethylene, 48 g. (0.575 mole), was prepared from the dibromomalononitrile-potassium bromide complex using Carboni's method (87). The yield of tetracyanoethylene was 55% and melted in the range of 192-1970 (sealed tube) (litera- ture value 201-202.5O (sealed tube)(87)). After vacuum sub- limation through charcoal at 150-1400/1 mm. Hg. its melting point was 201-2020 (sealed capillary tube). The Reaction of Dinitroacetylene with Thi0phene Noe-CEC-NOZ + I] J ——)- N02 8 N02 To a solution of dinitroacetylene (20 g., 0.25 mole) was added a precooled (50) solution containing 20 ml. of redis- tilled thiophene in 20 ml. of dried benzene during two hours. The reaction mixture was set aside for four days (50), during which a small quantity of a white solid precipitated. The solid was recovered on a Buchner funnel using No. 1 Whatman paper. The filtrate was returned to the flask and the latter was immersed in an ice bath. The solid was transferred to a watch glass, and in the process of transferring it from the filter paper with a metal spatula the material eXploded. After the filtrate had been set aside for an additional seven days at -50, it was allowed to warm to room temperature and left at this temperature behind a barricaded wall, for an additional three days. During this time the reaction 61 mixture had taken on a red-brown coloration. The benzene and excess thiOphene were removed in a rotary evaporator under reduced pressure yielding 84 g. quantity of a very dark reddish brown colored tarry residue. >A sodium fusion test of this material (several exploded before one was obtained) indicate the presence of nitrogen and the absence of sulfur. The above reaction was repeated except that diethyl ether was used as the solvent in place of benzene. A 15 ml. volume of the reaction mixture was transferred to a watch glass and the ether was removed with a stream of nitrogen gas leaving a residual yellowish oil. This oil exploded spontaneously at about 28°. Dinitroacetylene appears to be quite hazardous to handle in the laboratory. This material is mentioned in several places in the German Rocket Literature of the second world war. .A literature search did not disclose any actual proof that the material had ever been prepared. The analytical methods applied to this material gave very erratic results. The zinc reduction of the nitro groups was the primary analytical method used. 62 Attempted Preparation of Dimethyl-7-thiabicyclo[2.2.1]- heptadiene-Z,5¢dicarboxylate(2,§l_ _ 02% I OgCHs Caution: Dimethyl acetylenedicarboxylate is a very strong lachrymator. All Operations should be done in a hood. In a 250 m1., single necked, round bottom flask, was placed 5 g. (0.055 mole) of dimethylacetylenedicarboxylate, 5 ml. (5.45 g., 0.065 mole) of redistilled thiophene and 25 ml. of tetrahydrofuran redistilled from lithium aluminum hydride. The reaction mixture was set aside for seven days at room temperature. The solvent and excess thiOphene were removed in a rotary evaporator under reduced pressure. .A viscous liquid, 4.65 g., was recovered which gave a negative sulfur test using the sodium fusion-lead acetate method. The above procedure was repeated except the reaction was refluxed for 72 hrs. The flask was cooled and the solvent and excess thiophene were removed in a rotary evaporator under reduced pressure. A tar, 5.9 g., was recovered which gave a negative sulfur test using the sodium fusion-lead acetate method. ,The above procedures were repeated except that diethyl ether was used as the solvent. Neither of these reactions gave a product containing sulfur. 65 Attempted Preparation of 7—Thiabicyclej2.2.1]— heptadienejZ,Sédicarboxylic(2,5leacid C02H IIC02H In a 250 m1., single necked, round bottom flask, was placed 4 g. (0.055 mole) of acetylene dicarboxylic acid, 5 ml. (5.45 g., 0.065 mole) of redistilled thiophene and 25 ml. of tetrahydrofuran redistilled from lithium aluminum hydride. The reaction mixture was set aside for seven days at room temperature. The solvent and excess thiophene were removed in a rotary evaporator under reduced pressure. The solid re- covered weighed 4.1 g., and melted in the range 172-1750, the melting point of acetylenedicarboxylic acid. The solid gave a negative sylfur test using the sodium fusion-lead acetate method. The above procedure was repeated except the reaction was refluxed for 72 hrs. .The reaction flask was cooled and the solvent and excess thiophene were removed in a rotary evapor- ator under reduced pressure. A solid weighing 5.7 g., melting in the range 171-1760, was recovered. The solid gave a nega- tive sulfur test using the sodium fusion—lead acetate method. The above procedure was repeated except diethyl ether - was used in place of tetrahydrofuran. Neither reaction, under reflux or being set aside at room temperature, gave a reac- tion product containing sulfur. 64 Attempted Preparepion of 7-Thiabicyclo[2.2.1]- heptenetsidicarboxy(2.57anhydride (24) (5,6-endothio-A4-tetrahydrophthalic anhydride) In a 500 ml. single necked, round bottom flask, was placed 50 ml. (54.5 g., 0.65 mole) of redistilled thiOphene, 50 g. (0.51 mole) of maleic anhydride and 200 ml. of tetra- hydrofuran redistilled from lithium aluminum hydride. The reaction mixture was set aside for seven days at room temperature with continuous stirring by a magnetic stirrer. The solvent and excess thiophene were removed in,a rotary evaporator under reduced pressure. A solid weighing 49.0 g. was recovered and gave a negative sulfur test using the sodium fusion-lead acetate method. .The above reaction was repeated except the reaction mixture was heated at its reflux temperature for 24 hrs. The reaction flask was cooled and the excess solvent.and thiophene were removed in a rotary evaporator under reduced pressure, yielding 48.5 g. of a solid. The solid gave a negative sulfur test using the sodium fusion-lead acetate method. The above reaction was repeated except diethyl ether was used as the reaction solvent. .Again the product obtained did not contain sulfur. l 65 The above reaction was repeated a third time except that 200 ml. of excess thiophene was used as the reaction solvent. .Neither reaction, being set aside at room tempera- ture or heating it at its reflux temperature for 72 hrs., gave a reaction product containing sulfur. Attempted Preparation of 2-Cyano-7—thiabieyclo[2.2.115 heptepe .CN I In a 500 m1., single necked, round bottom flask, was placed 50 ml. (54.5 g., 0365 mole) of redistilled thiophene, 50 ml. (70 g., 1.5 moles) of redistilled acrylonitrile and 200 ml. of tetrahydrofuran redistilled from lithium aluminum hydride. The reaction mixture was set aside for one week at room temperature, during which time it became yellow in color. The excess solvent was removed in a rotary evaporator under reduced pressure. The light yellow colored tacky residue was twice tested qualitatively for sulfur by the sodium fusion—lead acetate method. The test results were negative. The reaction described above was repeated with the ex- ception that it was heated at its reflux temperature for 72 hrs. on a steam bath. After cooling the reaction mixture and removing the excess solvent and reactants in a rotary evaporator, the residue was tested for sulfur using the sodium fusion-lead acetate method. The test result was nega- tive. 66 The above reaction was repeated a third time substitut-. ing diethyl ether for the tetrahydrofuran and again only negative sulfur test results were obtained. The reaction was repeated a fourth and fifth time. One was set aside at room temperature for one week and the other was heated at its reflux temperature for 72 hrs. In both reactions the only solvent used was the thiophene and acrylonitrile. Both of the residues obtained from these reactions after removing the excess reactants gave negative tests for sulfur using the sodium fusion-lead acetate method. The above general eXperimental procedures were employed using acrylic acid and methyl acrylate with thiOphene in place of the acrylonitrile in an effort to obtain the endo- thiobicyclo compound. Under the conditions used, only a polymeric material was obtained which gave a negative sulfur test using the sodium fusion-lead acetate method. The Reaction of Tetracyanoethylene (45p43) with Thiophene CN NC CN \ / ll (I + /C=C\ -—->’ CN 3 NC CN . CN CN In.a tared 500 m1., three necked, round bottom flask equipped with a stirrer, reflux condenser and a dropping funnel, was placed 85 ml. of redistilled thiophene. The flask was cooled to 40 and the stirrer was started. The 67 cooling bath was removed and 1.28 g. (0.01 mole) of tetra- cyanoethylene (45,44) was added slowly to the reaction flask. There was no apparent reaction temperature rise. The stirred reaction mixture was allowed to warm to room temperature, during which time it became very dark amber-red in color. The reaction temperature was maintained at room temperature for 4 hrs., during which the reaction mixture's color changed to a light yellow. The excess thiophene was removed by distillation under reduced pressure. The recovered light yellow solid weighed 2.4 g., m.p.158-144O (sealed tube), and the odor of cyanide ion or cyanogen was very strong. Cairns et al. (45) recrystallized their reaction products from a benzene-cyclohexane solvent system. On attempts to recrystallize the above material, the solid turned dark brown in color and the crystals remaining weighed 0.8 g. and melted at 192-1940 (sealed tube). This corresponds to the melting point of tetracyanoethylene. No additional solid was recovered from the solvent when it was removed by distillation under reduced pressure. The Second Attempp to React Tetraeyano- ethylene with Thi0phene In the same apparatus as described above was placed 1.86 g. (0.014 mole) of tetracyanoethylene in 15 ml. of tetra- hydrofuran redistilled from lithium aluminum hydride. The solution was cooled to 40 by immersion in an ice bath and 68 10 ml. (11.98 g., 0.15 mole) of thiophene, in 25 ml. of redistilled tetrahydrofuran, was added to the stirred tetra- cyanoethylene solution dufing a 50 min. period. The reaction mixture was warmed to room temperature and kept at this temperature for 4 hrs. with constant stirring. The color of the reaction mixture changed from a dark red-yellow to a light amber color. At this point the contents of the flask were transferred to a tared flask using tetrahydrofuran. The solvent and thiophene were removed in a rotary evaporator under reduced pressure. The light yellow solid recovered, weighed 2.96 g. and had a strong odor of cyanide or cyanogen. (The flask was swept with dry nitrogen gas for 2 hrs. carrying the exiting gases into a flask containing potassium iodide. Iodine was liberated by the appearance of a brownish-red color in the aqueous solution. The appearance of free iodine indicated that cyanogen was being produced. In a 50 ml. burette was placed 55 ml. of chromatographic grade alumina. The light yellow reaction solid was dis- solved in benzene. The solution, which became dark amber in color, was poured onto the chromatographic column. The sec— tion of the column, where the sample was, turned black immediately, began to evolve a gas. The glass chromatographic column became extremely hot and broke. 69 A Third Attempt to React Tetraeyanoethylene with Thiophene The experimental procedure described above was repeated. After removal of the solvents and thiOphene, the solids were transferred to a large sublimator. The sublimator was evacuated to 0.5 mm. Hg. and was heated by immersion in an oil bath. The solid darkened and began to evolve a gas. No product was collected on the water condenser of the sublimator until the temperature of the oil bath reached 110-1200. A solid was then deposited. This solid melted at 195-1960 (sealed tube). This was tetracyanoethylene since a mixed melting point with an authentic sample was not depressed. The cold trap had the odor of hydrogen sulfide. The black residue from the sublimator was taken up in diethyl ether.’ The solution was filtered to remove insoluble materials and then cautiously warmed with hydrochloric acid (IN) on a steam bath for 2 hrs. No reaction had apparently taken place. The reaction mixture was filtered and the black residue which remained failed to melt below 2500. Its infrared spectrum was too complex for structural information to be obtained from it. A Fourth Attempt to React Tetraeyanoethylene with Thiophene The experimental procedure used was the same as that employed in the second attempt to conduct this reaction. Attempts to recrystallize the reaction solids from diethyl 7O ether failed. Upon heating the ether solution, it became very dark in color. The dark solid recovered from the ether solution was sealed in a melting point tube and the melting point determined. A glass like solid sublimed and this melted at 192-1940 (tetracyanoethylene) leaving in the bottom of the tube a black charred like residue. Ehe Fifth Attempt to React Tetracyanoethylene with Thiephene The experimental procedure used was the same as that employed in the second attempt to conduct this reaction. The solid product was heated with 50 ml. of hydrochloric acid (IN). Hydrogen sulfide gas was evolved as well as a gas which had an odor like cyanide. A black polymeric resi— due remained in the reaction flask. No further attempts to react tetracyanoethylene with thiOphene were undertaken because no reaction product, or proof of a reaction, having taken place yielding the endothiobicyclo bridged compound, could be obtained. Phe Attempted Preparation of 1,2,5,4-Tetrahydro- 5,6-dimethoxy-1L4-endothi0phthalic anhydride (2,5) 3 0 fl' CH30 C \ 0 CH3 / C \ 71 rIn a 100 m1., single necked, round bottom flask, equipped with a reflux condenSer fitted with a calcium chloride drying‘ tube, was placed 2.0 g. (0.014 mole) of 5,4-dimethoxythiophene and 2.0 g. (0.020 mole) of maleic anhydride in 20 ml. of dioxane redistilled from sodium metal. The reaction mixture was heated at its reflux tempera— ture for 4 hrs. and then it was cooled to room temperature by immersion in an ice bath. .The dioxane and other volitile materials were removed by vacuum distillation. The recovered residue was recrystallized twice from cyclohexane to obtain 1.67 g. of maleic anhydride (m.p. 49.5-50.50). A mixed melt— ing point of this material with an authentic sample of the anhydride was not depressed. The cyclohexane mother liquor used for the recrystal- lization was evaporated on a steam bath to obtain 1.1 g. of a liquid residue whose infrared spectrum was found to be identical to the infrared spectrum of 5,4-dimethoxythi0phene, indicating that the expected 1,2,5,4—tetrahydro-5,6-dimethoxy- 1,4-endothiophthalic anhydride (2,5) had not been obtained. The Attempted Preparation of 2,2,5,5-Tetracyano- 5,6-dimethoxy-1,4-dihydro-1,4-endothiobenzene CN CH30 CN CN In a 100 m1., single necked, round bottom flask, equipped with a reflux condenser fitted with a calcium chloride drying 72 tube, was placed 2.0 g. (0.014 mole) of 5,4-dimethoxythio- phene, 2.0 g. (0.016 mole) of tetracyanoethylene in 50 ml. of dioxane redistilled from sodium metal. The reaction mixture was heated at its reflux temperature for 4 hrs. The color of the reaction mixture became a dark blood red during the heating and on cooling to room temperature, a solid crystallized from the reaction mixture. The reaction mixture was set aside for 16 hrs. in a refrigerator at 100. The crude solid (5.7 g.) was collected on a Buckner funnel. It was in the form of light pinkish colored plate- lets and melted in the range of 78—1500. The solid was recrystallized from 10 ml. of a 1:1 benzenezcyclohexane mix- ture to obtain 0.7 g. of tetracyanoethylene. The "mother liquor" was reduced to 5 ml. in volume by a nitrogen gas stream. On cooling this concentrated solution to 100 for 60 min. an additional quantity of solid was obtained melting in the range 72-1140. During the melting, tetracyanoethylene sublimed onto the cooler portions of the sealed capillary tube. The solid appeared to be a molecular complex, discussed by Cairns et al. (45) rather than a chemical compound. Elemental analysis for C, H, N and S gave very erratic results. Elemental analysis calc'd for C12H8N4SOZ: C, 52.9; H, 2.94; N, 20.6; S, 11.76; Found: C, 60.71, 65.14; H, 1.91, 1.45; N, 24.06, 27.54; S, 8.57, 6.65 (64,65). 75 The solid obtained on being set aside for 72 hrs. became wet in appearance and turned brown in color. Based on the analytical results the expected 2,2,5,5—tetracyano- 5,6-dimethoxy—1,4—dihydro—1,4-endothiobenzene had not been obtained. The Attempted Preparation of 1,2L5J4-tetrahydrg- 5,6-dimethyl-1,4-endothi0phthalic anhydride(2,5); H3C _. C\=O 0 H3 - / c==o In a 100 m1., single neckedtpeareshaped flask, equipped with a reflux condenser fitted with a calcium chloride drying tube, was placed 2.00 g. (0.018 mole) of 5,4-dimethylthiophene, 2.0 g. (0.020 mole) of maleic anhydride in 50 ml. of dioxane redistilled from sodium metal. The reaction mixture was heated at its reflux temperature for 4 hrs. The dioxane and other volatile materials were removed by vacuum distillation, leaving a solid residue of 1.97 g. The residue after recrystal— lization from cyclohexane melted in the range 49.5-51.0. The material was identified as maleic anhydride by a mixed melting point determination with an authentic sample of maleic anhydride and by its infrared spectrum, which showed that the expected 1,2,5,4-tetrahydro-5,6-dimethyl-1,4-endothio- phthalic anhydride (2,5) had not been obtained. 74 The Attempted Preparation of 2,2,5,5-Tetracyano- 1,4-dihydro-5,6-dimethyl-1,4-endothiobenzene 1 cu H3O CN CN In a 100 m1., single necked, pear-shaped flask, equipped with a reflux condenser fitted with a calcium chloride dry- ing tube, was placed 5.6 g. (0.052 mole) of 5,4—dimethylthio- phene, 4.1 g. (0.052 mole) of tetracyanoethylene and 50 ml. of dioxane redistilled from sodium metal. The reaction mixture was heated at its reflux temperature for 4 hrs. The color of the reaction mixture changed to a dark "blood" red coloration during heating. The reaction mixture was cooled to room temperature and a solid crystal- lized from solution in the form of large platelets. The reaction mixture was set aside in a refrigerator for 16 hrs. at 10°. The solid was collected on a Buchner funnel. It weighed 6.7 g. and was in the form of light tan crystalline, plate— lets melting in the range 68 to 1200. Attempts to recrystal- lize the solid from 60 ml. of 1:1 benzene:cyclohexane mixture yielded a solid melting at 194-1960 (sealed tube). This was identified as tetracyanoethylene by a mixed melting point with an authentic sample of tetracyanoethylene and by its identical infrared spectrum to that of tetracyanoethylene. 75 The filtrate from the above recrystallization was concen— trated to 10 ml. in volume under reduced pressure and set aside in a refrigerator for 16 hrs. at 10°. There was ob— tained a second quantity of light tan colored platelets which melted at 194-1960 (sealed tube). Thus, the expected 2,2,5,5-tetracyano—5,6-dimethyl-1,4-dihydro—1,4-endothio- benzene had not been obtained. The blood red colored solution did indicate that a re- action had occurred and further the 6.7 g. of solid which were obtained would indicate a reaction had taken place. This solid could be the molecular complex discussed by Cairns et al. (45) which on attempts to recrystallize reverts back to the aromatic compound and tetracyanoethylene. The Attempted Preparation of 1,2,5,4rTetrahydro- 5,6-diphenyl—1,4-endothi0phthalic anhydride(2,5) O 0 (Reaction of 5,4-diphenylthi0phene with maleic anhydride) 0 V. O 0 ll \0’ n- O In a 100 ml. single necked, round bottom flask, equipped with a reflux condenser fitted with a calcium chloride drying tube, was placed 2.0 9. (0.0085 mole) of 5,4-diphenylthio- phene, 1.0 g. (0.010 mole) of maleic anhydride and 50 ml. of dioxane redistilled from sodium metal. 76 The reaction mixture was heated at its reflux tempera- ture for 4 hrs. The volume of the reaction mixture was then reduced to 10 ml. and it was set aside in a refrigerator for 16 hrs. at 50. A solid crystallized from the reaction mixture and was collected on a Buchner funnel. It was recrystallized from cyclohexane to obtain 1.7 g. of 5,4-di— phenylthiophene (m.p. 112-115.50). The original dioxane mother liquor and cyclohexane mother liquor were combined and the solvents were removed by evaporation on a steam bath. The solid residue was recrystallized from diethyl ether to obtain 0.85 g. of maleic anhydride (m.p. 50.0-52.50). A mixed melting point of this material with an authentic sample of the anhydride was not depressed. Thus, the expected 1,2,5,4-tetrahydro-5,6-diphenyl-1,4- endothiophthalic anhydride (2,5) had not been obtained. The Attempted Preparation of 2,2,5,5—Tetracyano- 5,6-diphenyl—1L4-dihydro—1,4-endothiobenzene CN ‘ CN CN (Reaction of 5,4-Diphenylthiophene with Tetracyanoethylene) O, c. In a 100 ml. single necked, round bottom flask, equipped with-a reflux condenser fitted with a calcium chloride drying tube, was placed 2.2 9. (0.0095 mole) of 5,4-diphenylthiophene, 77 1.4 g. (0.011 mole) of tetracyanoethylene in 50 ml. of dioxane redistilled from sodium metal. The reaction mixture was heated at its reflux tempera- ture for 4 hrs. The color of the reaction changed from a dark red brown to a light red during the reaction. The reaction mixture was cooled to room temperature and the dioxane was removed by distillation under reduced pressure yielding 5.5 g. of a light yellow crystalline solid (m.p. 108-109.50). The crude product was recrystallized from a. 1:,1 benzene:cyclohexane miXture. There was obtained 1.1 g. of tetracyanoethylene (m.p. 197-199O sealed tube) which did not give a mixed melting point depression with an authentic sample of the tetracyanoethylene. Further the infrared spectrum of the material isolated was identical to that of an authentic sample of tetracyanoethylene. The benzene:cyclohexane mother liquor from the recrystal- lization was evaporated to dryness on a steam bath. The solid residue was recrystallized from diethyl ether, yield- ing 2.1 g. of 5,4-diphenylthiophene. A mixed melting point of this material with an authentic sample of 5,4-diphenyl- thiOphene, was not depressed. Thus, the eXpected 2,2,5,5- tetracyano-S,6-diphenyl-1,4-dihydro-1,4-endothiobenzene had not been obtained. 78 The Preparation of 5,6,7,8-Dibenzo-1,2,5L4- tetrahydro—l,4-endothionaphthalene(2,5) enhydride (9) by the Reaction of;4,5,6,7- gibenzoisothiopephthalene with Maleic Anhydride In.a 100 ml. single necked, pear-shaped flask, equipped with a reflux condenser fitted with a calcium chloride dry- ing tube was placed 2.54 g. (0.010 mole) of 4,5,6,7-dibenzo- isothionaphthalene, 1.47 g. (0.015 mole) of maleic anhydride and 25 ml. of dioxane redistilled from sodium metal. The reaction mixture was heated at its reflux temperature for 4 hrs. and allowed to cool to room temperature by immersion in an ice bath. It was then concentrated to 10 ml. and an insoluble product separated from solution. The crude product was recrystallized twice from hexane to obtain 2.5 9. (0.0075 mole, 75% yield) of 5,6,7,8-dibenzo-1,2,5,4-tetrahydro—1,4- endothionaphthalic(2,5)anhydride melting in the range 216- 2190 (literature value m.p. 219-2200 (9)). Anal. Calc'd for Caongoasz' C, 72.40; H, 5.62; S, 9.65; Found: C, 72.57, 72.44; H, 5.67, 5.58; S, 9.59, 9.65% (64). A 0.5 9. sample of the product was refluxed for 4 hrs. with 5 ml. of methanol containing 0.5 ml. of concentrated hydrochloric acid. The solid isolated from this reaction 79 was only the starting material as was evidenced by comparison of its infrared spectrum with that of the original sample and by a mixed melting point with the original sample which was not depressed (m.p. 218-2200). A 0.5 g. (0.0015 mole) sample of the dibenzoendothio- naphthalene was fused with 2 g. of sodium hydroxide at 5000 for 15 min. The reaction product was dissolved in water, neutralized with hydrochloric acid and the solid collected, was recrystallized twice from benzene to obtain 0.51 g. (0.001 mole, 66.7% yield) of 5,6,7,8-dibenzonaphthalic(2,5) anhydride melting in the range 246-2520 (d) (literature value m.p. 248-250O (d)(9)) //0 \0/0\ 0 0 Anal. Calc'd for C20H1003: C, 80.55; H, 5.55; Found: C, 76.65, 79.77; H, 5.61, 5.58 (64). This product may have some acid present in it. The elemental analysis calculated for C20H1204 is C, 75.95; H, 5.79. Apparently some saponification—hydrolysis of the anhydride has occurred during the fusion with sodium hydroxide and in the subsequent isolation. 80 The Preparation of 112,5,415,6J7,8-Octahydro-1L4-endo- thionaphthalene(2,5)anhygride by the Reaction of 4,5,6,7- Tetrahydrobenzo[thhiOphene with Maleic Anhydride /O C/ \O/ C \ \O In a 100 ml. single necked, pear-shaped flask, equipped with a reflux condenser fitted with a calcium chloride drying tube, was placed 2.00 g. (0.014 mole) of 4,5,6,7-tetrahydro- benzo[C]thiophene, 1.50 g. (0.015 mole) of maleic anhydride and 25 ml. of dioxane redistilled from sodium metal. The reaction mixture was heated at its reflux temperature for 4 hrs. and then set aside for 16 hrs. at 50 in a refriger— ator. The product was recrystallized twice from hexane to obtain 1.65 g. (0.078 mole, 54.5%) of 1,2,5,4,5,6,7,8-octahydro- 1,4-endothionaphthalene(2,5)anhydride melting in the range 83-850 (d). Anal. Calc'd for C12H12038: C, 60.99; H, 5.12; S, 15.57; Found: C, 60.15, 60.45 (64,65); H, 4.97, 5.04 (65,64); S, 15.11, 15.54 (65,64). A 0.5 g. sample of the octahydroendothionaphthalene was refluxed for 4 hrs. with 5 ml. of methanol containing 0.5 ml. of concentrated hydrochloric acid. During the reaction time hydrogen sulfide was evolved as evidenced by its odor and by blackening of lead acetate test paper. The crude product (0.5 g.) isolated from the reaction was recrystallized twice from hexane and melted at 212-2140. Its infrared spectrum indicated that the anhydride functional group was 81 absent and the carboxyl group absorption was present. The qualitative test for sulfur by the sodium fusion-lead acetate method indicated that sulfur was absent in the product. A 0.5 g. sample of the 1,2,5,4,5,6,7,8-octahydro-1,4- endothionaphthalic anhydride, was fused with 2 g. of sodium hydroxide at 5000 for 15 min. The reaction product was dissolved in water, neutralized with hydrochloric acid (6N) and the solid obtained was recrystallized twice from benzene to obtain 0.27 g. of a solid, melting at 211-2140. This was identical to the solid obtained from the reaction of methan— olic hydrochloride and octahydroendothionaphthalic anhydride, as was evidenced by no mixed melting point depression and 2 both infrared spectra were identical. It is very probable that the solid product was 5,6,7,8- tetrahydronaphthalic(2,5)acid. COgH COZH Anal. Calc'd for C12H1204: C, 65.50; H, 5.50; Found: C, 64.97, 65.15; H, 5.95, 5.61 (64). The Preparation of 5,6,7,8-Dibenzo:2,2,5.5-tetragyep9+3,4- dihydro-1,4-endothionaphthalene by the Reaction of 4L5,6L7— Dibenzoisothionaphthalene with Tetracyanoethylene o - CN 00) ., O C” 82 In.a 100 ml. single necked, pear-shaped flask equipped with a reflux condenser fitted with a calcium chloride dry— ing tube, was placed 2.5 g. (0.011 mole) of 4,5,6,7-dibenzo- isothionaphthalene, 1.8 g. (0.014 mole) of tetracyanoethylene and 25 ml. of dioxane redistilled from sodium metal. .The reaction mixture was heated at its reflux tempera— ture for 4 hrs. and cooled to room temperature. The blood red colored reaction solution was then concentrated to 10 ml. and chilled to 50. The reddish colored solid which pre— cipitated was collected on a Buchner funnel and recrystal— lized three times from a 1:1 benzene-cyclohexane solvent to obtain 2.1 g. (0.0059 mole, 55.5% yield) of a solid melting in the range 262-2710 (d) which was tentatively identified as 5,6,7,8-dibenzo-2,2,5,5-tetracyano—1,4-dihydro-1,4-endo- thionaphthalene. (Anal. Calc'd. for C22H10N4S: C, 72.90; H, 2.76; N, 15.45; S, 8.85; Found: C, 72.55 (65); H, 2.71 (65); N, 15.61, 15.87 (65,64); 5, 8.73, 8.78 (64). A 0.5 9. sample of the product was refluxed for 4 hrs. with 5 ml. of methanol containing 0.5 ml. of concentrated hydrochloric acid. The reaction mixture turned a dark brown .and-a gas evolved during the reaction. The product isolated from this reaction was recrystallized three times from hexane to obtain 0.2 g. of a solid melting in the range 218-2200. Its infrared spectrum was identical to the infrared spectrum 85 of the 5,6,7,8-dibenzo-1,2,5,4-tetrahydro—1,4—endothio- naphthalene(2,5)anhydride. A mixed melting point of the two compounds was not depressed. The Preparation of 1L4L5y6,7,8-Hexahydro-2,215L§r tetracyano-l,4-endothionaphthalene by the Reaction of 4,5,6,7-Tetrahydrobenzon]thiophene with Tetra- eyanoethylene CN CN CN CN In a 100 ml. single necked, pear-shaped flask equipped with a reflux condenser fitted with a calcium chloride dry- ing tube, was placed 2.00 g. (0.014 mole) of 4,5,6,7-tetra- hydrobenzo[C]thiOphene, 2.0 g. (0.16 mole) of tetracyano- ethylene and 25 ml. of dioxane redistilled from sodium metal. The reaction mixture was heated at its reflux tempera— ture for 4 hrs. and cooled to room temperature. The orange red colored reaction solution was concentrated to 10 ml. and chilled at 50. The reddish colored solid which precipi- tated was collected on a Buchner funnel and recrystallized twice from a-1:1 benzene-cyclohexane mixture to obtain 2.4 g. (0.009 mole, 62.5% yield) of 1,4,5,6,7,8-hexahydro-2,2,5,5— tetracyano—1,4-endothionaphthalene melting in the range 154- 162° (d). This material was tentatively identified by elemental analysis. Anal. Calc'd for C14H10N4S: C, 65.15; H, 3.757 84 N, 21.06; S, 12.05; Found: C, 61.21 (65); H, 4.14 (65); N, 19.06 (65); S, 12.70, 12.15 (64). This material decomposed on being set aside at ambient conditions for two weeks. It was stable for months when stored under nitrogen atmosphere at 00. Attempts to make derivatives of this material by treat- ing with methanolic hydrogen chloride or sodium hydroxide fusion or hydrolysis of the nitrile groups with dilute hydrochloric acid led to extensive decomposition and only unidentifiable tarry materials were recovered. The Attempt to Prepare 1,4—Dihydro-1,4-endothio- naphthalene(The Reaction of Thiophene with Penzyne) I By a procedure similar to that of Wittig and Pohmer (56), thiOphene was caused to react with benzyne in the following manner. In a 500 ml. three necked, round bottom flask, equipped with a stirrer, condenser fitted with a calcium chloride drying tube, and a parallel adapter fitted with a gas inlet tube and a dropping funnel; was placed 1.5 g. (0.062 g. at.) of Grignard grade magnesium turnings. The apparatus was 85 swept with oxygen free dry nitrogen gas, while the magnesium turnings and reaction flask were heated by a "hot air gun" to remove moisture from the system. When the system was dry and had cooled to room tempera- ture, the magnesium turnings were covered with 12 ml. of tetrahydrofuran redistilled from calcium hydride and then 4.2 g. (0.05 mole) of redistilled thiOphene was added. The stirrer was started and a small crystal of iodine was added. The reaction flask and contents were heated at 500 until the iodine color disappeared, and then a solution of 8.7 g. (6 ml. 0.05 mole) of o-fluorobromobenzene (Beckwith Chemical Co.) in 12 ml. of tetrahydrofuran, redistilled from calcium hydride, was added. The reaction was initiated by heating the reaction flask with a hot air gun until the tetrahydro— furan commenced to reflux. The reaction mixture was stirred for 96 hrs. under a nitrogen atmosphere, cooled, and filtered to remove the excess magnesium. The magnesium residue in the reaction flask was extracted with three 50 ml. portions of diethyl ether. The combined reaction mixture and ether extracts were treated first with 150 ml. of 5% hydrochloric acid and then washed with two 50 ml. portions of water. The organic layer was dried over anhydrous magnesium sulfate and the volatile materials were removed by distillation under reduced pres- sure. The remaining brown viscous residue weighed 6.0 g. and had an odor similar to an ester or flavone. 86 The residue was dissolved in 20 g. of methylene chloride. Two, 20 ul. aliquots of this solution were in- jected into a Perkin—Elmer gas chromatograph having a G. E. silicone rubber column at 1500 (helium as a carrier, 15 ml./ min.). The chromatograms gave 14 and 20 peaks of which 8 and 11, respectively, were of about the same proportions. Two, 10 ul. aliquots of this solution were injected into a F & M gas chromatograph using a G. E. silicone rubber column and temperature programmed from 150 to 5000 (helium as carrier, 25 ml./min). The temperature of the injection port was 2500 and the temperature of the flame ionization detector was 5000. The two chromatograms gave 54 and 76 peaks, respective- ly. Many of the peaks were broad indicating very probably that appreciable thermal decomposition had occurred in the chromatograming. The infrared spectrum of a solvent freed residue of the above solution was extremely complex and indicated clearly that more than a single component was present. Qualitative tests using the sodium fusion—lead acetate method indicated that sulfur was present in fairly large amounts in the crude reaction products. Pecond Reaction of ThiOphene with Benzyne In a dry 500 ml. three necked flask, equipped with a stirrer, reflux condenser fitted with a calcium chloride 87 drying tube, adapter fitted with a gas inlet tube and a dropping funnel; was placed 4.0 g. (0.16 g. at.) of Grignard grade magnesium turnings, 17.6 g. (0.21 mole) of redistilled thiOphene and 20 ml. of tetrahydrofuran redistilled from calcium hydride. The system was flushed with dry oxygen free nitrogen gas and the reaction mixture was kept under a nitrogen atmos- phere for the duration of the reaction. To the stirred thio- phene magnesium suspension was added dropwise, a solution containing 18.1 g. (0.11'mole) of o-fluorobromobenzene and 20 ml. of tetrahydrofuran redistilled from calcium hydride. At the end of four days no apparent reaction had taken place. The reaction mixture was then heated by a "hot air gun" until the solvents commenced to reflux. The reaction initiation was evidenced by’a cloudy appearance in the re- action mixture. The reaction mixture was maintained at the reflux temperature for 24 hrs. The contents in the reaction flask at this point had become a dark brown viscous liquid with a sweet ester odor. The reaction product was dissolved in 50 ml. of diethyl ether, and the unreacted magnesium was removed by filtration. The filtrate was hydrolized with three, 100 ml. portions of saturated ammonium chloride to decompose any unreacted Grignard reagent and complex magnesium salts. The organic layer was then washed with 20 ml. of hydrochloric acid solu- tion (5%) and finally with two, 25 ml. portions of water. 88 Hydrogen sulfide was evolved during these washings as evi- denced by its odor and a lead acetate test paper test. The organic layer was separated, dried over anhydrous magnesium sulfate, and filtered into a tared 500 ml. single necked flask. The solvents and excess thiOphene were re- moved in a rotary evaporator under reduced pressure. A light brown viscous residue, weighing 12.0 g., was obtained. This material had a sweet ester odor. The crude product was fractionally distilled, to obtain two fractions; 2.7 g., b.p., 105-1110/0.15 mm. Hg., 2.1 g., b.p., 140-1450/O.15 mm. Hg. There was evidence of some decomposition having occurred during the distillation by the burnt odor and the dark brown color of the distillation residue. A light yellow colored solid was recovered from the dry ice trap used in the distillation apparatus and hydrogen sulfide was also present in the trap as evidenced by its odor and a lead acetate test paper test. The distillation residue was dissolved in chloroform, decolorized with Norite, filtered and set aside in a refrig- erator for 16 hrs. at 50 in an effort to obtain a crystal- line product, but without success. On removal of the chloro- form, a viscous tarry residue remained which weighed 6.8 g. The preceding vacuum distillates were combined and chromatographed onanlaluminum oxide column (Brock Activity I) using ligroin (60—900) as the eluent. The eluent was col- lected in 50 ml. fractions, and the solvent was removed from the fractions by an air sparge. 89 The first solid fraction obtained weighed 2.5 g. and melted in the range 55.0-56.50. This was identified as 2-phenylthiophene by comparison of its infrared spectrum with a spectrum of an authentic sample of 2-phenylthi0phene and by a mixed melting point, with an authentic sample of 2-phenylthi0phene, which was not depressed. The amount of this material obtained was 2.5 g. repre— sents 0.014 mole, or a 15% yield of 2-phenylthi0phene. After recrystallization from ethanol (95%), this material melted in the range 41.0-42.5O (literature values m.p. 55-560 (88) and 40-410 (89)). The second solid fraction obtained weighed 0.8 g. and had a melting range of 88.5—90.20. -After recrystallization from methanol, it melted in the range 90.5—91.50. The solid was identified as 5-phenylthiophene by comparison of its infrared Spectrum with the spectrum of an authentic sample of 5-phenylthiophene and by a mixed melting point of this material with an authentic sample of 5—phenylthiophene which was not depressed. The 0.8 g. of pure product obtained represents 0.005 mole, or a 4.5% yield of 5-phenylthiophene. A third solid was obtained and melted in the range 191- 1940 (56). This gave a negative qualitative sulfur test using the sodium fusion-lead acetate method. This was 0.8 g. of triphenylene (0.0055 mole, 5.2%) and was identified by a mixed melting point with an authentic sample of tri- phenylene which was not depressed and by the comparison of its infrared spectrum with the spectrum of triphenylene. 90 Further elution of the column with benzene yielded 0.6 g. of a colorless oil which gave a negative qualitative sulfur test. Microdistillation of this oil gave a product with a boiling range unsuitable for identification purposes. Its infrared spectrum indicated the presence of an aromatic group and additional unsaturation. This infrared spectrum appeared to be similar to the spectrum of dihydronaphthalene. The distillation residue was treated with various organic solvents in efforts to obtain a crystalline material, but were unsuccessful. The residue was then chromatographed on an aluminum oxide column (Brock's Activity I) and eluted with ligroin (60-900). ‘The first solid obtained weighed 0.1 g. and melted in the range 85-840. This material was identified as 2,5-diphenylthiophene by its infrared spectrum and its melting point (57). The second solid obtained weighed 0.5 g. and melted in the range 107-1110. On recrystal- lization from ethanol, it had a melting point of 112-1140 (74,78). -A mixed melting point of this material with an authentic sample of 5,4-diphenylthi0phene was not depressed. Further elution using a 2:1 ligroin:benzene mixture gave a third solid, weighing 0.5 g., which melted in the range 151-1550 (57). This material was identified as 2.5- diphenylthiophene by a mixed melting point with an authentic sample of 2.5-diphenylthi0phene which was not depressed (m.p. 146-147.5O (90.91)) and by comparison of its infrared spectrum to the spectrum of an authentic sample of the 2,5- diphenylthiophene. 91 A fourth solid, weighing 0.5 g., was obtained which melted.in the range 142-1440. The solid contained sulfur as shown by the sodium fusion—lead acetate test method and by its infrared spectrum did not appear to be a phenylthio- phene. Continued elution with a 1:1 ligroin:benzene mixture and finally by benzene gave four additional solids in trace quantities ((0.1 g.) with melting point ranges of 215-2160, 250-2520, 276-2800 and 514-5200, respectively. All of these solids contained sulfur as Shown by qualitative tests. Infrared Spectra of the solids were not sufficiently informa- tive for their identification. During the elution'some oily fractions, weighing 5.0 g., were obtained. which did not contain sulfur and these were discarded. Elution with chloroform after the benzene elution yielded a solid (0.8 g.) melting in the range 195-1980, and identi- fied as triphenylene. The Third Attempt to Prepere 1,4:pihydro—1,4- endothiopephthalene A 500 m1., three necked, round bottom flask was equipped with a stirrer, and two parallel adapters; one adapter fitted with a gas inlet tube, and a 100 ml. drOpping funnel, the other fitted with.a reflux condenser protected by a calcium chloride drying tube, and a 100 ml. dropping funnel. 92 The reaction flask was charged with 4.0 g. (0.17 g. at.) of Grignard grade magnesium turnings. The apparatus was then heated byra "hot air gun“ while dry oxygen free nitrogen gas was passed through the system to remove all moisture. After the apparatus and magnesium had been dried, 20 ml. of tetrahydrofuran redistilled from calcium hydride and a small crystal of iodine were added to the reaction flask. The stirred reaction mixture was heated by the "hot air gun" until the tetrahydrofuran was gently refluxing. The heating was continued until the iodine color had disappeared to activate the magnesium. The reaction flask and its contents were cooled to room temperature by an ice bath. In the first drOpping funnel was placed 19.2 g. (0.228 mole) of redistilled thiophene in 25 ml. of tetrahydrofuran redistilled from calcium hydride. In the second drOpping funnel was placed 18.7 g3 (0.107 mole) of o—fluorobromo- benzene in 25 ml. of tetrahydrofuran redistilled from calcium hydride. A few drops of the o—fluorobromobenzene solution were added to the stirred reaction mixture and was heated by the hot air gun until the tetrahydrofuran began to reflux and a cloudiness appeared in the reaction mixture. The remaining o-fluorobromobenzene solution was added drOpwise (60 min.) Simultaneously with the thiophene solution at a rate such that the thiOphene was in excess and that the reaction was not.abated. The reaction was slow to initiate and it was necessary to heat the mixture to sustain the 95 initial reaction. After 15 mins. the reaction was exothermic enough to maintain the solvent at its reflux temperature during the remaining addition of the o-fluorobromobenzene (45 min.). During this time the color of the reaction mixture changed from colorless to dark brown and the magnesium had nearly all reacted. The stirred reaction mixture was heated at its reflux temperature for an additional 16 hrs. and then cooled to room temperature. It was filtered to remove the unreacted mag- nesium using 25 ml. of tetrahydrofuran as a transfer agent. The filtrate was diluted with 100 ml. of diethyl ether and the complex magnesium salts were hydrolyzed with three, 100 ml. portions of a saturated ammonium chloride solution. Some gas evolution occurred and a strong odor of hydrogen sulfide was in evidence. The organic layer was washed with two, 100 ml. portions of water and dried over anhydrous magnesium sulfate. The dried organic layer was transferred to a tared flask and the volatile solvents were removed by vacuum distillation, to obtain 12.4 g. of a brown viscous material which had a sweet ester like odor. -Elemental analysis for sulfur gave 12.25% (64) (calculated for 1,4—dihydro—1,4-endothionaph- thalene, ClngS, S = 20.0%). The reaction product (11.0 g.) was vacuum distilled and the fraction (4.1 g.) distilling from 50-105°/0.05 mm.ng. was collected. This material was redistilled in a micro 94 vacuum distillation apparatus with four receivers. The following fractions were collected; 0.8 g. b.p. 60-850/ 0.05 mm. Hg., (3 = 10.96, 12.06% (64.66)); 1.8 g., b.p. 85-950/0.05 mm. Hg., (s = 19.80, 19.94% (64.66)); 0.6 g., b.p. 95-1050/0.05 mm. Hg., (3 = 1.42, 1.26% (64.66)); 0.4 g., b.p. 105-1250/0.05 mm. Hg., (5 = 1.54, 2.29% (64,66)). .The second fraction, b.p. 85—950/0.05 mm. Hg. having 19.80 and 19.94% sulfur was set aside in a refrigerator for 16 hrs.-at 00, to obtain 1.4 g. of a crystalline solid melt- ing in the range 55-560. This material was recrystallized three times from pentane yielding 1.1 g. (0.0089 mole. 6.4%) of 1,4-dihydro-1,4-endothionaphthalene, a clear crystalline solid melting in the range 78.5-80.00. This solid Slowly turns greenish on standing at room temperature, but remains colorless and stable when maintained at 00. The above preparation and isolation procedure was repeated three addi— tional times yielding 5.5 g. of the above 1,4-dihydro-1,4— endothionaphthalene. For structure proof 0.5 g. (5.1 mmoles) of this solid was refluxed for 4 hrs. with 5 ml. of methanol containing 1 ml. of concentrated hydrochloric acid. Some hydrogen sul- fide was evolved as evidenced by its odor. After the solution was refluxed, it was cooled, diluted with 10 ml. of water. .and made basic (pH 10) with sodium hydroxide. .To this basic solution was added 600 mg. of 2,4-dinitrochlorobenzene in 4 ml. of methanol. This solution was refluxed for 10 minutes 95 and then filtered while hot. The solution was cooled (5°) and the thioether allowed to crystallize from solution. The solid thioether was recrystallized twice from methanol, to obtain 0.58 g. (1.16 mmole, 57%) of 2.4-dinitrOphenyl— 1-naphthylthioether melting at 172.0—175.5o (literature value 174-1760 (69)). A mixed melting point with an authentic sample of 2,4—dinitrOphenyl-1-naphthylthioether was not depressed. The infrared’spectras (65) of both thioethers were identical. Anal. Calc'd. for C15H1004N23: N02 S—H 8‘“ N02 HGCl Na0 _____> ______9 , MeOH Cl N02 N02 C, 58.88; H, 5.10; S, 9.81; Found: C, 58.1 (64); H, 2.97 (64); S, 9.65, 9.47, 9.76, 9.58 (64.68). The basic solution from the thiobridge Opening reaction was extracted with methylene chloride. On evaporation of the methylene chloride, there was obtained some crystals of an Off white colored solid. The solid was recrystallized from n-pentane twice to obtain a solid melting at 80-810. This solid was identified as naphthalene by comparison of its 96 infrared spectrum with the Spectrum of an authentic sample of naphthalene and by,a mixed melting point with an authentic sample of naphthalene which was not depressed. The 1,4-dihydro-1,4-endothionaphthalene was submitted for elemental analysis. .Anal. Calc‘d for clngs: C, 74.96; H, 5.05; S, 20.01; Found: c, 71.19, 73.93 (65.64)); H, 5.66, 5.41 (63.64)); S, 19.80, 19.94 (65.64)). .The reaction of thiOphene with benzyne has been tried in several solvents; diethyl ether, tetrahydrofuran, dioxane, dimethylether of ethylene glycol and dimethyl sulfoxide. Diethyl ether was the first solvent tried. the reaction did not appear to occur because the products formed made a tacky ball picking up the magnesium turnings causing the reaction to cease. Dimethyl sulfoxide appeared to have many side reactions and it appeared that the Grignard reagent or the benzyne had added across the sulfur oxygen bond. Tetra— hydrofuran was chosen as the best solvent because of the ease in drying it, fewer side reactions, solvates the Grignard complexes and has a low boiling point which was helpful in product isolation. There were solids and oils isolated from this reaction which did not contain sulfur. .These were not investigated because of the number of sulfur containing compounds that were separated and studied. (If these other compounds had been identified, they might have added further proof of the forma- tion of the 1.4-endothiobridge. 97 Following the procedures described by Chernois, Entrikin and Hodnett (98) a 0.5 g. (0.005 mole) sample of 1,4-dihydro- 1.4-endothionaphthalene was heated under reflux, with 1.5 9. (0.0095 mole) of potassium permanganate, 25 ml. of water, 0.5 ml. of 6 N sodium hydroxide, until the purple color had nearly disappeared. The cooled reaction mixture was neutral— ized with dilute sulfuric acid, and then heated to boiling. The mixture was cooled and the precipitated acid collected and recrystallized three times from a (1:1) ethanol water mixture to obtain 0.18 9. (0.0015 mole, 98% yield) of phthalic acid melting at 204—2070 (literature value 205-2080 (98)). -A 0.10 9. (0.0007 mole) of the phthalic acid was heated with aniline and then recrystallized three times from methanol to obtain 0.16 9. (0.00052 mole, 75% yield) of the dianilide of phthalic acid melting at 255-2540 (literature value 255-2550 (98)). This indicated that the above was phthalic acid. .Mixed melting points with an authentic sample of the dianilide of phthalic acid was not depressed. -A 0.5 g. (0.0019 mole) sample of the 1,4-dihydro-1,4- endothionaphthalene was refluxed with 0.5 ml. of hydrobromic acid for 10 min. The solid was collected and recrystallized three times from hot ethanol. A sodium fusion-silver nitrate test indicated the absence of bromide ion. The solid melted at 80.5-81.5o and a mixed melting point with an authentic sample of naphthalene was not depressed. Comparison of its infrared spectrum with an authentic sample of naphthalene also indicated that this solid was naphthalene. 98 .A 0.5 9. (0.0019 mole) sample of the 1,4-dihydro-1,4- endothionaphthalene was reacted with three drOpS of bromine in chloroform. Two materials were isolated, a-bromonaph- thalene and 1,4-dibromonaphthalene (m.p. 81.5-85.00). Their infrared spectra were identical to the spectra of these materials which had been prepared previously in this study in preparing, a-thionaphthalene. The Reaction of 5L4-Dimethylthiophene with "Benzyne" (An Attempt to Prepare 2,5-Dimethyl—1L4edihydro-1,4- endothionaphthalene) CH3 CH3 // S + I —')' CH3 CH3‘\~ A 500 ml. three necked, round bottom flask was equipped with a stirrer and two parallel adapters; one of the adapters was fitted with a gas inlet tube and a 50 ml. drOpping funnel, the other with a reflux condenser, protected by a calcium chloride drying tube, and a 50‘ml. drOpping funnel. The reaction flask was charged with 2.9 g. (0.12 g. at.) of Grignard grade magnesium turnings. The apparatus was heated with a “hot air gun" while dry oxygen free nitrogen gas was passed through the system to remove moisture. Follow- ing the drying Operation 20 ml. of tetrahydrofuran redistilled from calcium hydride and a small crystall of iodine was added to the magnesium.. The stirrer magnesium suspension was 99 heated until the iodine color had disappeared. The reaction flask and contents were cooled to room temperature by an ice water bath. In one dropping funnel was placed a solution containing 18.7 g. (0.101 mole) of o-fluorobromobenzene in 25 ml. Of tetrahydrofuran redistilled from calcium hydride. In the other dropping funnel was placed a solution containing 12.5 g. (0.111 mole) of 5,4—dimethylthiophene in 25 ml. of tetra- hydrofuran redistilled from calcium hydride. A few drops of the o-fluorobromobenzene solution were added to the stirred reaction mixture and it was heated with a “hOt air gun" until the tetrahydrofuran commenced to reflux gently and a white cloudiness appeared in the reaction mixture. The remaining o-fluorobromobenzene and 5,4-dimethylthio— phene solutions were then simultaneously added dropwise during 90 min. The reaction was slow to initiate and it was neces- sary to heat the reaction mixture to sustain the initial reaction. .After approximately a quarter of the reactants had been added the exothermic reaction was sufficient to maintain the tetrahydrofuran at its reflux temperature. During the addition of the reactants the color of the reaction mixture changed from a milky white to a reddish-brown. Following the addition of the reactants the mixture was heated at its reflux temperature for an additional hour and then stirred at room temperature for 16 hrs. It was filtered to remove unreacted magnesium using 25 ml. of tetrahydrofuran 100 as a transfer agent. "Diethyl ether (100 ml.) was added and the complex mag- nesium salts were hydrolyzed with three, 100 ml. portions of saturated ammonium chloride. Some gas evolution occurred and the Odor of hydrogen sulfide was detected. The organic layer was separated, washed with 100 ml. of water and dried with anhydrous magnesium sulfate. The solvents were removed by distillation under reduced pressure to obtain 15.7 g. of a light brown oil with a sweet ester like Odor. (Anticipated obtaining 20 g. of 2.5—di- methyl-1,4-dihydro-1,4-endothionaphthalene.) To the reaction product was added 10 ml. of diethyl ether and this mixture was set aside in a refrigerator at 50 for 16 hrs. The precipitated solid was collected on a Buchner funnel to Obtain 0.7 g. of terphenylene (m.p. 195.0- 196.50) identified by no depression of a mixed melting point (m.p. 194-1970) with an authentic sample of terphenylene and by comparison of the infrared spectrum of this solid with a spectrum of an authentic sample of terphenylene which were identical. A thin layer chromatographic analysis of 20 ug. samples of the original reaction product using ethyl acetate-chloro- form and benzene-chloroform eluents indicated that only a single component was present. Gas chromatographic analysis of a 0.01 mg. sample on a temperature programmed apparatus (150-2500, 100/min.) using a Versamide column (5') and a flame detector (He 8.5. Air 120, 101 Hz 5.0 ml./min.) gave Six major peaks (155, 157, 166, 210, 225, 2450) and four minor peaks (157, 176, 255, 2600). A 1.0 g. sample of the original product was distilled in a micro distillation apparatus. Two drops of a distillate, b.p. 60-700/0.07 mm. Hg. were collected and on continued heating some liquid appeared to be refluxing in the column at 110-1200/0.07 mm. Hg. The column was rapidly cooled in an attempt to collect a sample of the liquid. The infrared Spectrum of the distillate, liquid in the column and the dis— tillation residue appeared to be identical and no separation had occurred. The infrared spectrum of the distillation residue was identical to the original reaction produced even though it had been heated to 2500 with the exception of an absorption band at 5.6u which had disappeared during the heat- ing period. Elemental analysis for sulfur on a sample of the reaction product after removing the terphenylene gave 5.70 and 5.76% sulfur. Sulfur calculated for C;2H128 is 17%. (A 1.0 g. sample of the reaction product, was chroma— tographed on a 1/2"-8" alumina column (Broch Activity I) elut- ing with cyclohexane, to Obtain ten, 50 ml. fractions. On removing the cyclohexane, fractions 4-9 (light yellow Oils, combined weight -0.8 g.) appeared to have identical infrared Spectra and these appeared identical to the spectrum of the starting material, which indicated that the expected separa- tion had not been obtained. 102 - + CH3 H 'CH3 CH3 M°°fl CH3 A 1.0 9. sample of the original reaction product was refluxed for 4 hrs. in 10 ml. of methanol containing 2 ml. of concentrated hydrochloric acid. Hydrogen sulfide was evolved as was evidenced by its odor and by a lead acetate paper test. The solution was diluted with 10 ml. of water and made basic (pH 10) with sodium hydroxide. This solution was ex- tracted with three, 10 ml. portions of methylene chloride to remove all organic substances except the sodium salt of the mercaptan (sodium thionaphthanate). The infrared spectrum of the residue after removal of the methylene chloride from the extract (0.9 g.) appeared to be identical to the spec- trum of the original reaction product except for the appear- ance of an absorption band at 5.86 H. The basic solution obtained above possibly containing the sodium thionaphthanate was acidified with hydrochloric acid (5%) and the acid solution was extracted with three, 10 ml. portions of methylene chloride. On removal of the methylene chloride there was obtained 0.05 g. of a yellow waxy material having a "sour odor". (The infrared spectrum was different from the starting material; the 11.65 H absorption 105 band had disappeared; the 5.60 u band had disappeared and new adsorption bands at 7.9 u. 8.4 u, 10.5 u were found.) The waxy solid was dissolved in 2 ml. of methanol and made basic with sodium hydroxide (5 drops 6N) and then 0.1 g. of 2,4-dinitrochlorobenzene was added to the solution. The mixture was heated at its reflux temperature for a half hour and set aside at 50 for 2 hrs. The solid isolated was 2.4- dinitrochlorobenzene (m.p. 49.5-51.00). The expected 2,4- dinitrOphenylthioether was not found. 0 ‘ CH3 $132 ‘COZH + H02C‘C02H CH3 C02H HOgC COgH A 1.0 9. sample of the original reaction product was refluxed for 2 hrs. with 5.0 g. of potassium permanganate, 55 ml. of water and 0.5 g. of sodium carbonate (98). The reaction mixture was cooled and acidified carefully with dilute sulfuric acid (6N). The manganese dioxide and excess permanganate were destroyed with solid sodium bisulfite. The solution was cooled to 50 and filtered to remove the precipitated acidic material. The crude acid melted in the range 92-1810. The acidic solution Obtained above was extracted with three, 10 ml. portions of methylene chloride. On removal of the methylene chloride a light tan crystalline solid residue was obtained melting in the range 55-1040. 104 The two acidic solids were combined (0.61 g.) and chromatographed on a 1/5"-6“ alumina column (Broch Activity I) eluting with cyclohexane. Traces of benzoic acid were found (identified by infrared spectrum comparison and mixed melting point tests) as well as phthalic acid. In addition an acidic material (m.p. 56—590) and traces of other acidic material not in sufficient quantity to determine their melting point or structure were also found. A sample of the original reaction product, dimethyl- thiOphene and benzyne, was submitted for elemental analysis. Anal. Calc'd. for C12H1283 C, 76.7; H, 6.57; S, 17.0; Found: C, 79.1; H, 10.97; S, 5.70, 5.76; Halogen as Cl, 5.54. The reaction between 5,4-dimethylthiophene and benzyne did not yield the expected product 2,5-dimethyl-1,4-dihydro- 1,4-endothionaphthalene. The product appeared to be a com- plex mixture which was very stable. On standing at room temperature for 6-7 weeks, no apparent decomposition had occurred. The Reaction of 5,4-DimethoxythiOphene with "Benzyne" in an Attempt to Prepare 2,5-Dimethoxy-1,4-dihydro- TL4-endothionaphthalene CH O //' CH 0 ‘\~ CH30 CH30 105 This preparation was carried out in the same apparatus described above for the reaction of 5,4-dimethylthiophene with benzyne, using 2.8 g. (0.11 g. at.) of Grignard grade magnesium turnings, 15.0 g. (0.104 mole) of 5,4-dimethoxythio~ phene and 20.0 g. (0.114 mole) of o-fluorobromobenzene. The reaction product was isolated as previously described and after the solvents were removed by distillation under reduced pressure, there was obtained 19.6 g. of a brown Oily product which had a sweet ester-like odor. Elemental analysis for sulfur gave 12.5% S (64). A thin layer chromatographic separation of a 0.8 9. sample of the product in 25 ml. of ethyl acetate, using ethyl acetate and chloroform elution gave a major spot, a minor spot and two trace spots. The major and minor spots fluoresced under ultraviolet light and both turned brown after a 10 min. exposure to iodine vapors. The original product (18.5 g.) was dissolved in 20 ml. of diethyl ether and set aside in a refrigerator for 16 hrs. at -50. A crystalline solid separated from solution and was collected by filtration on a Buchner funnel, to obtain 0.7 g. (0.005 mole) of terphenylene melting at 194-1960. Its infra- red Spectrum was identical with a spectrum of an authentic sample of terphenylene and a mixed melting point with an authentic sample of terphenylene showed no depression (m.p. 193-195°). A 1.0 9. sample of the original reaction product was distilled in a short path high vacuum distillation apparatus. 106 Two fractions were collected; 0.2 g., b.p. 60-900/0.005 mm. Hg., and 0.2 g., 90—110C/0.005 mm. Hg. The infrared spectras of the two fractions appeared to be identical to the starting material. NO additional distillate was Obtained by heating the sample to 2000 (still temperature) but decomposition occurred in the still as evidenced by the residue turning black and by the burnt odor. SH “ OCH3 / ‘ OCH3 OCHs + + H25 OCHs CH3°H \ OCH3 OCH3 A 0.5 g. sample of the reaction product was refluxed for 4 hrs. with 5 ml. of methanol containing 1 ml. of concentrated hydrochloric acid. Hydrogen sulfide was evolved as evidenced by its odor and by a lead acetate paper test. The solution was diluted with 10 ml. of water, made basic (pH 10) with sodium hydroxide and extracted with three, 15 ml. portions of methylene chloride. The basic solution was labeled, B-1, and set aside. The infrared Spectrum of the residue after removal of the methylene chloride was different from the original starting material. The Spectrum did not have 5,4u absorption band (-S-) and the methoxyl group absorption could not be observed. Attempts to identify the Oily material as 2.5- dimethoxy-l,4-dihydronaphthalene or 2,5-dimethoxynaphthalene were unsuccessful. .The oily residue was refluxed with basic potassium per— manganate for 4 hrs. The excess permanganate was destroyed 107 with sodium bisulfite. (The solution was made acid with 5% hydrochloric acid and extracted with methylene chloride. The infrared spectrum of the residue after removal of the methylene chloride indicated the presence of a carboxyl group but that a methoxyl group was absent. The oxidized material was chromatographed on a 1/2"-6" alumina column and yielded traces of benzoic acid (mixed m.p. not depressed), phthalic acid (mixed m.p. not depressed) and other additional acidic materials. The basic solution, B-1, obtained by refluxing the re- action product with methanolic hydrogen chloride, was acidi— fied with 5% hydrochloric acid and extracted with methylene chloride. The methylene chloride was removed by a nitrogen sparge to obtain 0.2 g. of a light yellow waxy solid which had no definite melting point. A 50 mg. sample of this material was dissolved in methanol, made basic with sodium hydroxide, and then reacted with 100 mg. of 2,4-dinitrochlorobenzene in an unsuccessful attempt to prepare a thioether. A 0.2 g. sample of the original reaction product was fused for 15 min. with 1 g. of sodium hydroxide at 515°. The residue was dissolved in water and neutralized with 5% hydrochloric acid, but no material separated from solution. The acid solution was extracted with three, 15 ml. portions of methylene chloride. On removal of the methylene chloride, there was obtained a light yellow solid melting in the range 108 164-1820 (d) whose infrared spectrum was very complex. Recrystallization of the solid from ethanol, benzene and then chloroform failed to alter its infrared spectrum. The melting range after several recrystallizations was 186.5-188.5O (d). A sodium fusion and lead acetate test indicated the absence of sulfur. A 5 9. sample of the original reaction product was chromatographed on a 1"-12" alumina column using cyclohexane as the eluent, to obtain eighteen 100 ml. fractions. The infrared spectra's of fractions 4 through 10 were identical. These seven fractions were combined and on removal of the solvent yielded a pale yellow oil (5.1 g.). A sample of the oil was submitted for elemental analysis. Anal. Calc'd. for clngaogs: C, 65.45; H, 5.45; O, 14.54; S, 14.54. Found: c, 62.71, 63.11; H, 7.34, 6.84 0, {16.3, 17.1}; ‘0 S, 15.62, 15.96 (64). The reaction product from the reaction product of 5,4- dimethoxythiophene with "benzyne" could not be identified as the expected 2,5-dimethoxy-1,4-dihydro-1,4-endothionaphthalene. The reaction productcnlbeing set aside for a few weeks changed from a light yellow colored material to orange-brown in color and had a very disagreeable odor. The distilled fractions on being set aside for a few weeks also underwent a color change from a bright green (2 weeks) to almost black (4-5 weeks). 109 The Reaction of 5,4-Diphenylthi0phene with "Benzyne" in an Attempt to Prepare 2,5-Diphenyl-1L4-dihydro- 1J4-endothionaphthalene This preparation was carried out in the apparatus described above for the reaction of 5,4-dimethylthiophene with benzyne using 2.8 g. (0.11 g. at.) of Grignard grade magnesium turnings, 17.6 g. (0.071 mole) of 5,4-diphenyl- thiophene and.14.6 g. (0.085 mole) of o-fluorobromobenzene. The reaction product was worked up as previously described and after the solvents were removed by distillation under reduced pressure, there was obtained 22.8 g. of a brown viscous Oil with an ester odor. The oil was dissolved in 50 ml. of diethyl ether and set aside in a refrigerator (00) for 2 hrs. A solid separated from solution and was collected by filtration on a Buchner funnel. 5,4—DiphenylthiOphene, 10.6 g. (0.045 mole), was recovered and identified by a mixed melting point (m.p. 110.0-112.50) with an authentic sample of 5,4-diphenylthi0phene which was not depressed. Comparison of the infrared Spectrum of the isolated 5,4—diphenylthiOphene with that of an authentic sample indicated the two were identi— cal. The filtrate from the treatment of the reaction product with diethyl ether was concentrated to 50 ml. and set aside 110 in a refrigerator for 16 hrs. at -50. No additional 5.4- diphenylthiOphene was recovered. The ether solution was heated (400) to remove the ether and the recovered light orange viscous residue was chromatographed on an alumina column using cyclohexane as the eluent. The eluting solvent was collected in 100 ml. fractions. The fractions 5 through 7 appeared to be identical as indicated by their infrared Spectra. These fractions were combined and gave 8.6 g. of a light orange viscous oil on removal of the solvent. The oil was submitted for elemental analysis. Anal. Calc'd. for canges: C, 84.57; H, 5.16; 8, 10.27; Found: C, 82.40, 81.14; H, 4.97, 4.89; 8, 10.96, 11.51 (64). The oily product was tested for the eXpected endothio- bridge. S H Ofl. H3 0 A 0.1 9. sample of the oil was refluxed for 4 hrs. with 5 ml. of methanol containing 1 ml. of concentrated hydro— chloric acid. Hydrogen sulfide was evolved as evidenced by its Odor. The solution after refluxing was diluted with 10 ml. of water, made basic (pH 10) with sodium hydroxide and extracted with three, 10 ml. portions of methylene chloride. The infrared spectrum of the residue after removal of the methylene chloride appeared to be identical to the original product. 111 The basic solution was acidified with 5% hydrochloric acid and extracted with three, 10 ml. portions of methylene chloride. On removal of the methylene chloride a white solid was obtained melting in the range 202-2110. The infra- red spectrum of this solid indicated the presence of a carbonyl group. Attempts to prepare a 2.4-dinitrOphenyl— thioether derivative of this solid were unsuccessful. A 0.5 9. sample of the original oily product was refluxed with 2 g. of Raney nickel in 25 ml. of absolute ethanol for 24 hrs. The reaction mixture was filtered to remove the nickel residue and the ethanol was removed by distillation under reduced pressure. Qualitative tests on the residue for sulfur by the sodium fusion and lead acetate method indi- cated that sulfur was absent. The infrared spectrum, of the Raney nickel treated material, indicated the 5.4 u sulfur band had been removed. The material unfortunately could not be crystallized. Attempts to identify this residue failed to give any information other than it was a compound contain- ing both aromatic and aliphatic groups. A 0.5 g. sample of the original oily product was refluxed with basic potassium permanganate solution (98). The excess permanganate was destroyed with sodium bisulfite. The re- action mixture was made acid with 5% hydrochloric acid and extracted with three, 20 ml. portions of methylene chloride. The infrared spectrum of the "paste" residue after removal of the methylene chloride indicated the presence of a carboxyl group. Further identification was not undertaken. 112 A 0.5 9. sample of the original oily product was heated 15 min. with 2 g. of sodium hydroxide at 5150. The residue was dissolved in 25 ml. of water and neutralized with 5% hydrochloric acid. NO crystalline material separated from the acidified solution. The acidic solution was extracted with methylene chloride and on removal of the methylene chloride a "pasty residue" was Obtained which melted in the range 62-1580. The infrared spectrum of this was extremely complex and fur- ther identification work was not undertaken. The reaction between 5,4-diphenylthiophene and benzyne appeared to have taken place. A light yellow viscous Oil was isolated but could not be identified as the expected product; 2,5-diphenyl-1,4—dihydro—1,4-endothionaphthalene. The Preparation of 6,7,8,9-Dibenzo-5L10-dihydro- 5,10-endothioanthracene by the Reaction of 4,5,6,7— Pebenzoisothionaphthalene with "Benzyne" In.a 250 ml. three necked, round bottom flask, equipped with a stirrer and two parallel adapters; one equipped with a gas inlet tube and a 50 ml. drOpping funnel, the other with a reflux condenser protected by a calcium chloride dry— ing tube and a 50 ml. dropping funnel; was placed 0.5 g. (0.015 g. at.) of Grignard grade magnesium turnings. 115 The apparatus was heated with a "hot air gun" to remove moisture while dry oxygen free nitrogen gas was flowing through the apparatus. Tetrahydrofuran, 10 ml. redistilled from calcium hydride, was added to the reaction flask and a small crystal of iodine was added to catalyze the reaction. While stir- ring the magnesium suspension, the flask was heated until the iodine color disappeared. The reaction flask was then cooled to room temperature by immersion in an ice water bath. In one dropping funnel was placed 1.8 g. (0.015 mole) of o-fluorobromobenzene in 5 ml. of tetrahydrofuran redis- tilled from calcium hydride, and in the other drOpping funnel was placed 2.2 9. (0.0094 mole) of 4,5,6,7-dibenzo- isothionaphthalene in 20 ml. of tetrahydrofuran redistilled from calcium hydride. While stirring the magnesium suspen— sion, a few drops of the o-fluorobromobenzene solution were added and the reaction mixture was heated at its reflux temperature by a "hot air gun" until a white cloudiness ap- peared in the reaction mixture. The remaining o-fluorobromobenzene solution and the dibenzoisothionaphthalene solution were Simultaneously added dropwise. The reaction flask was heated occasionally to maintain the reaction temperature at 40-450. The reaction appeared to be complete in 2 hrs. after which the reaction mixture was heated to its reflux tempera— ture for 10 min. and cooled to room temperature. The mixture 114 was filtered to remove the unreacted magnesium and then diluted with an equal volume of diethyl ether. The magnesium complex was hydrolyzed with three, 10 ml. portions of saturated ammonium chloride solution. Hydrogen sulfide gas was evolved as evidenced by its odor. The organic layer was separated, dried with anhydrous magnesium sulfate and the solvents and other volatiles were removed under reduced pressure in a rotary evaporator. The tan colored product, 2.68 g., was dissolved in methylene chloride (10 ml.) and decolorized with activated charcoal. After filtering, the methylene chloride was removed by a nitrogen gas stream and the off-white product was recrystal- lized three times from cyclohexane to obtain 1.96 9. (0.0065 mole, 68.2% yield) of 6,7,8,9-dibenzo-5,10-dihydro-5,10- endothionaphthalene melting at 186-1880. Anal. Calc'd. for C22H14S: C, 85.12; H, 4.54; S, 10.52. Found: C, 84.96, 85.27 (64); H, 4.51, 4.07 (64); 8. 10.06, 10.18 (64). A 0.5 9. sample of the 6,7,8,9-dibenzo-5,10-dihydro- 5,10-endothionaphthalene was refluxed for 4 hrs. with 5 ml. of methanol containing 0.5 ml. of concentrated hydrochloric .acid. A solid reaction product was recovered melting at 176.0-177.5°. Qualitative sulfur tests on this material by the sodium fusion-lead acetate method were negative. Elemental analysis gave C, 94.55-and H, 5.44. It is very probable that the solid was dihydrodibenzoanthracene as 115 suggested by the carbon and hydrogen calculations. .000 Anal. Calc'd for dihydrodibenzoanthracene, ngng: C, 94.28; H, 5.72. -Anal. Calc'd for dibenzanthracene (a,7) or dibenz(a,c)- anthracene, C22H14: C, 94.92; H, 5.08. A 0.5 9. sample of the 6,7,8,9—dibenzo-5,10-dihydro- 5,10—endothionaphthalene was fused with 2 g. of sodium hydroxide at 5000 for 15 min. The reaction mixture was cooled to room temperature, dissolved in 10 ml. of water and neutralized with (6N) hydrochloric acid. The solid product was collected on a Buchner funnel and recrystallized from benzene. The solid reaction product melted at 199.5-202.50. Qualitative sulfur test on this material by the Sodium fusion-lead acetate method were negative. This solid prob- ably was dibenzanthracene (92,95). A mixed melting point determination with an authentic sample of dibenzanthracene was not depressed and comparison of its infrared spectrum with the spectrum of an authentic sample of dibenzanthracene indicated they were identical. 116 Preparation of 5,6,7,8,9L10-Hexahydro-9,1O- endothionaphthalene by the Reaction of 4L5.§L7- Tetrahydrobenzo[C]thiOphene with "Benzyne“ 1::0 oarfo In a 250 ml. three necked, round bottom flask, equipped with a stirrer and two parallel adapters; one equipped with a gas inlet tube and a 50 ml. drOpping funnel, the other with a reflux condenser protected by a calcium chloride drying tube and a 50 ml. drOpping funnel; was placed 0.40 g. (0.016 g. at.) of Grignard grade magnesium turnings. The apparatus was heated with a "hot air gun" to remove moisture while dry oxygen free nitrogen gas was flowing through the apparatus. After the apparatus was dry and cooled, a 10 ml. volume of tetrahydrofuran redistilled from calcium hydride was added to the flask. A small crystal of iodine was then added and the flask was heated at the reflux temperature of the tetrahydrofuran until the iodine color had disappeared to initiate the reaction. The reaction flask was cooled to room temperature by immersion in an ice water bath. In one drOpping funnel was placed 2.6 g. (0.015 mole) of o-fluorobromobenzene in 5 ml. of tetrahydrofuran redis- tilled from calcium hydride and in the other dropping funnel was placed 2.0 g. (0.015 mole) of 4,5,6,7-tetrahydrobenzo[C]- thiophene in 10 ml. of tetrahydrofuran redistilled from 117 calcium hydride. While stirring the magnesium suspension, a few drops of the o-fluorobromobenzene solution were added and the reaction flask was heated by a "hot air gun" at the reflux temperature of the tetrahydrofuran and a white cloudi- ness appeared in the reaction mixture. The remaining o-fluorobromobenzene solution and tetra- hydrobenzo[C]thiophene solution were simultaneously added dropwise. The reaction mixture was occasionally heated to maintain=the reaction temperature between 40-450. The re— action appeared to be complete after 2 hrs. The reaction mixture was then heated to its reflux temperature for 10 min., cooled to room temperature and it was filtered to remove the unreacted magnesium. .The filtrate was diluted with an equal volume of diethyl ether. (The reaction mixture was treated with three, 10 ml. portions of saturated ammonium chloride to decompose any complex magnesium Salts. Some hydrogen sulfide was evolved during this treatment as evidenced by its Odor. The organic layer was separated, dried with anhydrous magnesium sulfate and the solvents and other volatiles were removed under reduced pressure in a rotary evaporator. The light brown crystalline solid, 2.1 g., was dissolved in methylene chloride and decolorized with activated charcoal. The methylene chloride was removed by a nitrogen gas stream. The yellowish colored solid was recrystallized three times from cyclohexane to Obtain 1.64 9. (0.0076 mole, 52.8% yield) 118 of 5,6,7,8,9,10-hexahydro-9,10—endothioanthracene melting at 67.0-68.50. Anal. Calc'd. for C14H14S: C, 78.51; H, 6.54; S, 14.95; Found: C, 78.46, 78.52 (64): H, 6.41, 6.48 (64): S, 14.87, 14.81 (64). Peegtion of Methanolic Hydrochloric Acid with 5L6L7,8,9,10—Hexahydro-9y10-endothioanthracene A 0.5 g. sample of the hexahydroendothioanthracene was refluxed for 4 hrs. with 5 ml. of methanol containing 0.5 ml. of concentrated hydrochloric acid. The solid reaction product was recovered and melted at 74.0-76.50. Qualitative sulfur tests on the solid by the sodium fusion and lead acetate method were negative. It is very probable that the solid was 1,2,5,4-tetrahydroanthracene. Anal. Calc'd. for C14H14: C, 92.26; H, 7.74; Found: c, 91.71, 91.54 (64); H, 8.04, 8.26 (64). However the analysis would indicate that it was a hexahydro— anthracene, C14H15: C, 91.19; H, 8.75. Reaction of 5,6,1y8,9y10-Hexahydro-9,10-endothio— epthreeene with Sodium Hydroxide A 0.5 g. sample of the hexahydroendothioanthracene was fused with 2 g. of sodium hydroxide at 5000 for 15 min. The reaction product was dissolved in water and neutral— ized with hydrochloric acid (6N). The solid which separated was collected on a Buchner funnel and recrystallized three 119 times from cyclohexane to Obtain 0.51 g. of a solid melting in the range 75-1040. Repeated recrystallization from methanol gave a solid melting at 76.0-78.50. A qualitative test for sulfur on the product was negative. The mixed melting point of this product with the product from the reaction of methanolic hydrogen chloride with hexahydro- endothioanthracene was depressed (m.p. 64-670). The infra- red spectras of the two products appeared to be identical, .and were assumed to be 5,6,7,8,9,10-hexahydroanthracene. SUMMARY .1. The compound, 4-chlorocyclohexene oxide, an inter— mediate in the attempted preparation of 1—hydroxy-7-thio- bicyclo[2.2.1]heptane, was synthesized for the first time by the epoxidation Of 4-chlorocyclohexene with peracetic acid. 2. The Diels-Alder adduct of 1,2,5,4,5,6,7,8-octahydro- 1,4-endothionaphthalene(2,5)anhydride was synthesized for the first time from 4,5,6,7—tetrahydrobenzo[C]thiOphene. 5. Thi0phene. 5,4—dimethyl-, 5,4-dimethoxy-, or 5.4-diphenylthiOphene failed to undergo a Diels-Alder re- action with maleic anhydride or tetracyanoethylene. 4. 4,5,6,7-Tetrahydrobenzo[c]thiophene and 4,5,6,7- dibenzoisothionaphthalene both reacted with tetracyano- ethylene to give Diels-Alder adducts, reported here for the first time. These adducts are 1,4,5,6,7,8-hexahydro—2,2,5,5— tetracyano—1,4-endothionaphthalene and 5,6,7,8-dibenzo-2,2,5,5- tetracyano—l,4-dihydro-1,4-endothionaphthalene respectively. 5. 5,4-Dimethyl-, 5,4-dimethoxy-, and 5.4-diphenylthio— phene did react with benzyne but attempts to isolate the respective Diels-Alder adducts were unsuccessful. 120 121 6. Thi0phene did react with benzyne to give the Diels- Alder adduct in low yields. This is the first reported syn- thesis of 1,4-dihydro-1,4-endothionaphthalene at moderate conditions. 7. 4,5,6,7-Dibenzoisothionaphthalene and 4,5,6,7—tetra— hydrobenzo[C]thiophene did react with benzyne to give the respective Diels-Alder adducts, reported here for the first time. They are 6,7,8,9-dibenzo-5,10-dihydro-5,10-endothio- anthracene and 5,6,7,8,9,10-hexahydro-9,10-endothioanthracene. BIBLIOGRAPHY 10. 11. .12. 15. BIBLIOGRAPHY Birch, 8., Dean R., and Hunter, N., J. Org. Chem., 25, 1026 (1958). Van Tamelen, E. E., J. Am. Chem. Soc., 15, 5444 (1951); Org. 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APPENDIX APPENDIX EXPERIMENTAL Preparation of 5-Phenylthiopene I OH -C-CH3 -é-CH2CH3 + CH3CH2MgBr —>' He I2, A -H20 Y I I I \ +3.1.— "=C-H \\ // A,200 T I- S CH3 CH3 m.p. 91.5-92.0° Preparation of Methyethyl_Phenyl Carbinol Using the method of Brown and Voronkov (94) acetophenone, 152 g. (1.1 moles), was reacted with 155 g. (1.0 mole) of ethyl magnesium bromide. From product isolation procedures, there was obtained 147 g. (0.99 mole) of crude methylethyl phenyl carbinol (90% yield). 128 129 Preparation of dLB-Dimethyl Styrene Again using the method of Brown and Voronkov (94), the methylethyl phenyl carbinol, 147 g. (0.99 mole) described above was reacted with iodine (0.5 g.) at 2000. The reaction mixture was distilled to Obtain d,8-dimethylstyrene, 111 g. (0.84 mole, 85% yield, b.p. 67-70°/11 mm. Hg.). Preparation of 5-Phenyl Thiophene Again employing the method of Brown and Voronkov (94), 0.8-dimethylstyrene, 88 g. (0.66 mole) described above was reacted with sulfur (5 g. at.) at 2000 for 20 hrs. After product isolation, the crude 5-phenylthiOphene was sublimed and then recrystallized three times from methanol to obtain 21 g. (0.15 mole, 19% yield) of 5—phenylthiOphene melting at 91.0-91.5O (literature value 91.5-92.0O (94.57)). The infrared spectrum was Obtained, Figure IX. Preparation of 2-Phenyl Thiophene H //CH - c\\ - =CH-CH=O + CHg—C=0 M c--c=0 g I AcOH H / \ S\\§rJHI S\\§//NH I I NaOH COgH 12 //C Cu, A 4f a CH . - KMDOq, I Quinoline HS-C// J\ I c02H 150 Preparation of Rhodanine Adduct Using the method of Campaigne and Cline (95) cinnamalde— hyde, 59 g. (0.5 mole) and rhodanine, 40 g. (0.5 mole) were heated in a sodium acetate-glacial acetic acid mixture. After the reaction was complete, 0.5 hr., the reaction product was poured onto ice, filtered, and the solid product recovered by filtration was recrystallized twice for ethanol (95%) to obtain 50 g. (0.20 mole, 66%) of the rhodanine adduct (m.p. O 225 (95)). Preparation of Mercaptoacrylic Acid Employing the method of Campaigne and Cline (95), 50 g. (0.20 mole) of the rhodanine adduct was reacted with sodium hydroxide (90 ml., 10% solution) in 5 l. of water at 850 for 0.5 hr. After acidification of the mixture the precipitate was collected on a filter to obtain 26 g. (0.12 mole, 62%) of the crude mercaptoacrylic acid. Preperation of 2-Phenyl—5—carboxy Thi0phene Again employing the method of Campaigne and Cline (95), 21 g. (0.10 mole) of the mercaptoacrylic acid described above was reacted with 25 g. (0.2 mole) of iodine in absolute ethanol for 16 hrs. at 25°. The reaction mixture was then poured into 2 l. of water, and the excess of iodine was destroyed by sodium bisulfite and the precipitate was 151 collected on a filter. After air drying the precipitate for 16 hrs., it was dissolved in a sodium hydroxide solu- tion (5 l. of 2%) and treated with 40 g. of potassium permanganate. The excess potassium permanganate was des- troyed with sodium bisulfite and the solution was made acid with dilute hydrochloric acid. The precipitate formed was collected on.a filter and dried (1050) to obtain 12.0 g. (0.06 mole. 62%) of 2-phenyl-5-carboxythiophene melting at 182-1850 (literature value, m.p. 185-1870 (95)). Preparation of 2-Phepylthiephene Again employing the method Of Campaigne and Cline (95), the 12 g. (0.06 mole) of 2-phenyl-5—carboxthiOphene described above was reacted with 44.5 g. (0.14 mole) of mercuric acetate at 1400 for 5 hrs. The mixture was then acidified with 50 ml. Of concentrated hydrochloric acid and the 2-phenylthiOphene was recovered by steam distillation. The steam distillate was extracted with diethylether. (The ether was removed by distillation and the crude 2-phenyl- thiOphene was partially purified by sublimation. .The sub- limate was recrystallized 5 times for ethanol (95%) to obtain 6.4 g. (0.04 mole, 62%) of 2-phenylthiOphene melting at 32.0-32.5° (literature values, m.p. 35-350 (95), 43-45° (57). 40-410 (89)). .Infrared spectrum was Obtained. Figure X. .152 Preparation of d-Nephthalenethiol SH 90 Using the method of Dunigan (96) and Bost, Turner and Conn (69), 62.1 g. (0.5 mole) of 1-bromonaphthalene (K and K Laboratories) was reacted with 7.4 g. (0.51 g. at.) of Grignard grade magnesium turnings in 500 ml. of dry diethyl ether. After all of the 1-bromonaphthalene had been added the mixture was warmed in a hot water bath for a 0.5 hr. and 9.6 g. (0.5 g. at.) of sulfur was cautiously added to the reaction mixture. The reaction was exothermic and the diethylether tended to boil off. When all the sulfur had been added, the reaction mixture was warmed for an additional 0.5 hr. The mixture was then poured into 500 ml. of a saturated ammonium chloride solution. The diethyl ether layer was separated, and the aqueous layer was extracted twice with 50 ml. portions of diethyl ether. The combined ether extracts were extracted with three, 50 ml. portions of 6N sodium hydroxide. -The combined alkaline extracts were acidified with 110 ml. of 6N hydrochloric acid. The acidified solution was extracted with diethyl ether, and the ether extract was dried with anhydrous magnesium sul- fate. The ether extract and 1-thionaphthalene were trans- ferred to a distillation apparatus and the ether was removed under reduced pressure. The 1-thionaphthalene was distilled 155 and the fraction boiling at 158-1650/20 mm. Hg. was col- lected. It weighed 28.6 g. (0.18 mole, 60% yield) and had a refractive index of n30 1.6799 (literature value, b.p. 20 1.6802 (69.96)). 1610/20 mm. Hg. nD Preperation of 2,4-Dinitrephenyl—i-naphthyl Thioether N02 N02 CD Using the method of Bost, Turner and Conn (69), 6 g. (0.057 mole) of 1-thionaphthalene in 50 ml. of methanol was reacted with 1.5 g. (0.058 mole) of sodium hydroxide in 10 ml. of water. The sodium salt of thionaphthalene solution was added to 12 g. (0.06 mole) of 2,4-dinitrochlorobenzene in 40 ml. of methanol. The reaction mixture was heated at its reflux temperature for 20 min. and then filtered rapidly. The filtrate was cooled in an ice bath and the solid thio- ether was collected on a Buchner funnel. The crude thioether was recrystallized three times from methanol to obtain 5.8 g. (0.018 mole, 48%) of 2,4-dinitrOphenyl-1-naphthylthioether melting at 174.5-175.5° (literature value 176° (69)). Anal. Calc'd for C17H1004Ngs: S, 9.81 Found: 5, 9.68, 9.72, 9.55% (64). Infrared spectrum was obtained, Figure XI. ~154 Preperation of Tetraphepylthiophene (Thionessal) 0H0 USing the method of Baumann.and Fromm (91) 56 g. (0.20 mole)of trans stilbene (K and K, Laboratories) was heated at 2500 in a reflux apparatus with 10 g. (0.51 g. at.) Of sulfur until all evolution of hydrogen sulfide ceased. The crude thionessal was recrystallized five times from ethanol (95%) to obtain 20 g. (0.051 mole, 50%) of pure product melt- ing at 182.5-184.0O (literature value 178° (91)). ‘ Preparation of 2,4-Diphepylthiephene S 0 Using the method of Campaigne (97), 40 g. (0.55 mole) of acetophenone in 500 ml. of absolute ethanol was cooled to 00 by immersion in an ice bath. -Dry hydrogen chloride gas was passed into the solution until a slow rate of gas influx could be regulated and until 140 g. (5.84 moles) of hydrogen chloride (amount calculated to saturate the ethanol) had been added (approximately 6 hrs.). 155 Simultaneously, with the hydrogen chloride gas, hydrogen sulfide was passed into the solution. During the addition of the gaseous reactants the reaction mixture was kept at 00 by immersion in an ice bath. .When all of the hydrogen chloride gas had been added, the ice bath was removed and as the reaction mixture was warmed to room temperature, hydro- gen sulfide gas was passed continuously into the mixture. After the reaction mixture had been warmed to room temperature, the hydrogen sulfide was passed into it for an additional 8 hrs. The reaction mixture, after the 14 hrs. of reaction time, was set aside in a refrigerator for 16 hrs. to allow crystallization of the product. This was collected by fil- tration and was recrystallized twice from acetone to Obtain 21 g. of product melting at 107-108°. A 21 9. quantity of the product was dissolved in 500 ml. of dry xylene and 50 g. of copper powder was added to the mixture. The mixture was brought to its reflux temperature and stirred for 5 hrs. It was then cooled, filtered and the excess xylene was removed by vacuum distillation. The crude 2,4-diphenylthiOphene was recrystallized four times from boiling methanol to obtain 11 g. (0.047 mole, 28%) of 2.4-diphenylthiOphene melting at 120.5-121.0° (literature value, 121.0-121.5° (97)). The infrared spectrum was obtained, Figure XII. 156 Preparation of 2.5—Drphenylthiephene (90) U Using the method of Kapf and Paal (90), 46.5 g. (0.2 mole) of diphenacyl (K and K Laboratories, dibenzoylethane) was reacted with 25 g. (0.11 mole) of phosphorous pentasulfide at 160-1700 for 20 to 50 min. The reaction mixture was cooled and then vacuum distilled. The crude 2.5-diphenyl- thiOphene was washed with 80 ml. of 5N sodium hydroxide solu— tion and then with three, 50 ml. portions of water. The 2.5- diphenylthiophene was then recrystallized four times from boiling methanol to Obtain 26 g. (0.11 moles, 55%) Of a pure product melting at 155-1560 (literature value 1560 (90)). The infrared Spectrum was Obtained, Figure XIII. Preparation of 2y5-Diphenylthigphene H CH2 -C-CH2 -CH3 _.MgBr -CH2 —g—-—CH2CH3 0 + —-> I2 ! A 'HgO , / 0 _4,5 -CH2-— ==CH-CH3 L\~,/L~ 22A , 2000 s O m.p. 83.5-84.0 157 Preparation of Benzyl Etgyl Phenyl Carbinol Using the method of Brown and Voronkov (94), 100 g. (0.675 mole) of 1-phenyl-2-butanone (Aldrich Chemical Co.) was reacted with 0.69 moles of phenyl magnesium bromide. After product isolation procedures, there was Obtained 155 g. (0.595 mole) of crude ethylphenylbenzylcarbinol (88% yield). Preparation of d-Beneyl-fiemethyl Styrene (1,2-diphenyl-2-butene) Again employing the method Of Brown and Voronkov (94) the ethylphenylbenzylcarbinol (0.60 mole) described above was reacted with iodine (0.5 g.) at 2000. The reaction mix- ture was distilled to obtain 1,2-diphenyl-2-butene (0.46 mole, 76.5% yield, b.p. 142-150°/11 mm. Hg.) Preparation of 2,5-Diphenylthiophene Again employing the method of Brown and Voronkov (94) the 1,2-diphenyl-2-butene (95.5 g. 0.46 mole) described above was reacted with sulfur (5 g. at.) at 2000 for 20 hrs. After product isolation procedures the crude 2.5-diphenyl- thiOphene was sublimed and recrystallized five times from boiling methanol to Obtain 2,5-diphenylthiophene (42 g., 0.18 mole, 59%) melting at 85.5-84.0o (literature value m.p. 83.0-84.00 (57)). 158 Anal. Calc'd. for C16H128: C, 81.55; H, 5.08; S, 15.55; Found: C, 80.96, 81.21; H, 4.91, 4.96; S, 15.61, 15.58, 15.51 (64). The infrared spectrum was obtained, Figure XV. 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