RETURNING MATERIALS: IVIESI_J FThce in book drop to LIBRARIES remove this ChGCkOUt from “ your record. FINES win be charged if book is returned after the date stamped below. PART I SYNTHESIS OF A NEW DIARYNE EQUIVALENT AND ITS APPLICATION TO ORGANIC SYNTHESIS PART II ACID-CATALYZED AND PHOTOCHEMICAL REARRANGEMENTS OF NOVEL KETONES Dong OR A DISSERTATION Submitted to Michigan State University in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY Department of Chemistry 1985 Qil/QQ av“ ”1“ ABSTRACT PART I SYNTHESIS OF A NEI DIARYNE EQUIVALENT AND ITS APPLICATION TO ORGANIC SYNTHESIS PART II ACID-CATALYZED AND PHOTOCHEIICAL REARRANGEIENTS OF NOVEL KETONES by Dong OK In the first part of this thesis the synthesis of a new diaryne equivalent and its application to bis-annulation was investigated. Treatment of benzo[1,2-d:4,5-d']bistriazole 1 in aqueous potassium hydroxide solution at 66-68°C with hydroxylamine-O- sulfonic acid provided a mixture of 1,5- 1,6- and 1,7-diamino- benzo[1,2-d:4,5-d'Jbistriazole (2, 3, and 4) and two mono- aminated products in 45 and 48% yield respectively. The three isomers were separated in excellent purity by fractional recrystallization from ethanol. The mono-aminated products could then be recycled to give additional 2-4. Reaction of either 2 or 4 with lead tetraacetate (LTA) and two equivalents of a diene gave bis-annulation products. For example, reaction of 2 with diethyl 2,5-dimethylfuran-3, 4-dicarboxy1ate and LTA gave tetraethyl 1,4,5,8-tetrameth- yl-l,4,5,8-tetrahydroanthracene-1,4:5,8-diendoxide-2,3,6,7-te~ tracarboxylate as a single isomer in 67% yield. Similar reactions with the following symmetric dienes are also described: furan, 2,5-dimethylfuran, 1,3,4-trimethy1-2,5-di- phenylpyrrole, 2,3-bis-(methylene)-bicyclo[2.2.1]heptane, diethyl 3,4-furandicarboxy1ate. The question of regioselectivity arises when the diene is unsymmetric. Two regioisomers, as well as syn and anti stereoisomers, are possible. However, in practice only the 'trans'-type isomers were formed.*with several dienes. For example, treatment of 2 with methyl 2-furoate and LTA gave dimethyl 1,4,5,8-tetrahydroanthracene-1,4:5,8-dien- doxide-1,5-dicarboxy1ate in 47% yield. The following unsym- metrical dienes were studied: 3-bromofuran, dimethyl 4,5-di- phenylfuran-Z,3-dicarboxylate, 2,3,4,5,6,6-hexamethylcyclo- bexa-2,4-dien-1-one 5. Cycloaddition to 1,3—dipoles is also possible. v Here too the reaction was highly regioselective. For example, the reaction of 2 with N-methyl-(x-phenylnitrone and LTA gave the only the 'trans' regioisomer. The remarkable degree of regio- and stereospecificity in these cycloadditions strongly suggests that they occur in a stepwise manner, the regiochemistry being controlled by the mOno-aryne adduct. Bis-annulation has been extended to the synthesis of various polyphenyl arenes. For example, treatment of 2 with two equivalents of tetraphenylcyclopentadienone and LTA gave 1,2,3,4,5,6,7,8-octapheny1anthracene. Similarly, reaction of 2 with 1,3-diphenylisobenzofuran furnished the diadduct, 5,7,12,14-tetraphenyl-5,7,12,14-tetrahydropenta- cene-5,14,7,12-diendoxide 6 in 88% yield. Removal of the oxygen bridges from 6.by treatment with Zn-TiCl4 in boiling THF gave 5,7,12,14-tetraphenylpentacene 7 in 81% yield. Diels-Alder reaction of the pentacene 7 with dimethyl acetylenedicarboxylate or maleic anhydride gave the expected adduct at the centralaromatic ring. Part II of this thesis deals with aromatic acid-catalyzed and photochemical rearrangements of novel ketones, obtained directly or indirectly from the chemistry developed in Part I. The acid-catalyzed rearrangment of a [3,7’-unsaturated ketone, 1,3,3,4,7,8,10,12,12,13,16,17-dodecamethyl-benzo- [1,2-e:4,5-e']bisbicyclo[2.2.2]oct-7.16-dien-2,11-dione 8 (obtained from the reaction of diene 5 with 2 and LTA), in trifluroacetic acid gave an equilibrium mixture of four isomeric ketones (9-12), 1,5,6,7,8,8,10,11,12,14,17,17— dodecamethyl-benzo[1,2-c:4,5-f']bisbicyclo[3.2.1]oct-6,11-dien-2, 13-dione 9 (48%), 1,5,6,7,8,8,10,11,11,13,16,17-dodecameth- y1-benzo[1,2-c:4,5-e']bicyclo[3.2.1]octabicyclo[2.2.2]oct-6,- 16-dien-2,12-dione 10 (20%) 1,5,6,7,8,8,10,11,12,13,17,17-do- decamethyl-benzo[1,2-c:4,5-c']bisbicyclo[3.2.1]oct-6,11-di- en-2,14-dione 11 (15%) and 1,3,4,5,8,8,10,11,12,14,17,17-do- decamethyl-benzo[1,2-f:4,5-f']bisbicyclo[3.2.1]oct-3,11-di- en-2,13-dione 12 (9%). The structure determination of ketones (9-12) follows from their spectra and the results of deuterium labeling experiments. A solution of 11 in acetone was irradiated for 12 h, using a 450 watt Hanovia lamp and a Pyrex filter, to give virtually pure photoisomer, 1,2,4,7,8,8,10,11,12,12,13,15-do- decamethyl-benzo[1,2-e:4,5-e']bistricyclo[2.1.1.02v7]oct-3,14- dione 13. Irradiation of a benzene solution of syn-7,8-syn-16. 17-diepoxy-1,3,3,4,7,8,10,12,12,16,17,17-dodecamethyl-benzo[1, 2-e:,4,5-e']bisbicyclo[2.2.2]oct-2,11-dione 14, prepared in 85% yield from the reaction of 8 and m-chloroperbenzoic acid, in a similar fashion gave a decarbonylated diepoxide in quantitative yield. TO NY PARENTS ii ACKNOWLEDGEIENTS I wish to express my sincere appreciation to Professor Harold Hart for his enthusiasm, encouragement and guidance throughout the course of this study. Appreciation is extended to Michigan State University, National Science Foundation, and National Institute of Health for financial support in the form of teaching and research assistantships. Many thanks go to my parents, my sister and my wife Hyun for their support and. constant encouragement during these years. TABLE OF CONTENTS Chapter page LIST OF TABLES. . . . . . . . . . . . . . . . . . . . . . xii APPENDIX. xiii PART I. SYNTHESIS OF A NEW DIARYNE EQUIVALENT AND ITS APPLICATION TO ORGANIC SYNTHESIS. . . . . . . 1 INTRODUCTION. . . . . . . . . . . . . . . . . . . . . . . . 2 RESULTS AND DISCUSSION. . . . . . . . . . . . . . . . . . 20 A. Synthesis of Diamino-benzo[1,2-d:4,5-d'] bistriazole (DABT), A new Useful 1,4-Diben- zyne Equivalent. . . . . . . . . . . . . . . . . . 20 B. Use of a New Diaryne Equivalent, (DABT), in bis-annulation. . . . . . . . . . . . . . . . . 33 C. Preparation of Polyphenylarenes Using DART. . . . . . . . . . . . . . . . . . . . . . . 6O EXPERIEMTNAL 1. General procedures. . . . . . . . . . . . . . . . 74 2. Diethyl 2,5-diamino-1,4-benzenedi- carboxylate (44). . . . . . . . . . . . . . . . . 74 3. 1,5-Bis[acetylamino]-2,4-dinitroben- zene (51). . . . . . . . . . . . . . . . . . . . 75 4. 1,7-Diacetylbenzo[1,2-d:4,5-d']bis- triazole (53). . . . . . . . . . . . . . . . . . . 75 iv Chapter 10. 11. page Amination of benzo[1,2-d:4,5-d']bis- triazole (39) with Hydroxylamine-O- sulfonic Acid (54). . . . . . . . . . . . . . . . 76 a. 1,5-Diamino-benzo[1,2-d:4,5-d'] bistriazole (DABT) (40). . . . . . . . . . . 77 b. 1,7-Diamino-benzo[1,2-dt4,5-d'] bistriazole (41). . . . . . . . . . . . . . . 77 c. 1,6-Diamino-benzo[1,2-d:4,5-d'] bistriazole (63). . . . . . . . . . . . . . . 77 d. 1-Amino-benzo[1,2-d:4,5-d']bis- triazole (64). . . . . . . . . . . . . . . . 78 0-(2,4-Dinitropheny1)hydroxylamine (57). . . . . 78 Amination of benzo[1,2-d:4,5-d']bistri- azole with 0-(2,4-dinitrophenyl)hydrox- ylamine. . . . . . . . . . . . . . . . . . . . . 79 1,4,5,8-Tetramethyl-1,4,5,8-tetrahydro- anthracene-l,4:5,8-diendoxide (73). . . . . . . . 8O 1,4,5,8-Tetrahydroanthracene-1,4:5,8- diendoxide (71). . . . . . . . . . . . . . . . . 81 1,4,5,8-Tetramethy1-1,4,5,8-tetrahydro- anthracene-l,4:5,8-diendoxide (73) from (41). . . . . . . . . . . . . . . . . . . . . . . 32 1,4,5,8-Tetramethy1anthracene (75). . . . . . . . 32 Chapter 12. 13. 14. 15. 16. 17. 18. 19. 20. Bis-(N-methyl)-2,3,6,7-tetramethy1- 1,4,5,8-tetraphenyl-1,4,5,8-tetra- hydroanthracene-l,4:5,8-bisimine (80). Reaction of 40 with 2,3-bis(methylene)- bicyclo[2.2.1]heptane (83). Tetraethyl 1,4,5,8-tetrahydroanthra- cene-1,4:5,8-diendoxide-2,3,6,7-tetra- carboxylate (87). Tetraethyl 1,4,5,8-tetramethyl-1,4,5,8- tetrahydroanthracene-l,4:5,8-diendoxide- 2,3,6,7-tetracarboxylate (89). Dimethyl l,4,5,8-tetrahydroanthracene- 1,4:5,8-diendoxide-1,5-dicarboxylate (91). Aromatization of dimethyl 1,4,5,8- tetrahydroanthracene-l,4:5,8-dien- doxide-1,5-dicarboxylate (91). Dimethyl 2,3-diphenyl-3-hydroxy-2,3- dihydrofuran-4,5-dicarboxylate (97). Dimethyl 4,5-diphenylfuran-2,3-dicar- boxylate (98). Tetramethyl 3,4,7,8-tetraphenyl-1,4,5,8- tetrahydroanthracene-l,4:5,8-diendoxide- 1,2,5,6-tetracarboxylate (99). vi page 83 84 84 85 86 86 87 87 88 Chapter 21. 22. 23. 24. 25. 26. 27. 28. 29. 2,6-Dibromo-l,4,5,8-tetrahydroanthra- cene-1,4:5,8-diendoxide (101). Bis-[Z-Methyl-B-phenyl-Z,3-dihydro]benzo- [1,2-d:4,5-d']diisoxazole (107). N-Methyl-a- 2,4,6-trimethylphenyl- nitrone (108). Bis-[2-methyl-3-(2',4',6'-trimethyl- phenyl)-2,3-dihydro]benzo[1,2-d:4,5-d'] diisoxazole (109). Attempted synthesis of 1,4-dimethyl- 1,4,5,8-tetrahydroanthracene-l,4:5,8- diendoxide (110). Reaction of 40 with one equivalent of 2,5-dimethylfuran and one equivalent of lead tetraacetate (LTA). Attempted reaction of 1-amino-benzo [1,2-d:4,5-d']-bistriazole 64, with 2,5-dimethylfuran and lead tetraacetate. 1,3,3,4,7,8-Hexamethyl-5,6-bis(Z,Z- cyanomethylene)-bicyclo[2.2.2]oct—7- en-2-one (116). Reaction of 1,6-diamino-benzo[1,2-d:4,5-d'] bistriazole 63 with two equivalents of lead tetraacetate. vii page 89 89 90 90 . 91 92 -93 93 . 94 Chapter page 30. Reaction of l,5-diamino-benzo[1,2-d:4,5-d'] bistriazole 40 with one equivalent of lead tetraacetate. . . . . . . . . . . . . . . . . . . 94 31. Reaction of 1,5-diamino-benzo[1,2-d:4,5-d'] bistriazole 40 with lead tetraacetate in the presence of 1,1-dimethoxyethylene. . . . . . 95 32. 1,2,3,4,5,6,7,8-Octaphenylanthracene (125). . . . . . . . . . . . . . . . . . . . . . 95 33. Tetramethyl 2,3,6,7-tetraphenyl anthracene-1,4,5,8-tetracarboxylate (128). . . . . . . . . . . . . . . . . . . . . . 95 34. Bis-(N-methyl)-1,2,3,4,5,6,7,8-octa- phenyl-l,4,5,8-tetrahydroanthracene- 1,4:5,8-bisimine (130). . . . . . . . . . . . 96 35. 1,4,5,8-Tetrapheny1-1,4,5,8-tetra- hydroanthracene-1,4:5,8-dien- doxide (133). . . . . . . . . . . . . . . . . . . 97 36. 5,7,12,14-Tetraphenyl-5,7,12,14-tetra- hydropentacene-5,14:7,12-diendoxide (140). . . . . . . . . . . . . . . . . . . . . . 97 37. 5,7,12,14-Tetraphenylpentacene (141). . . . . . . 98 38. Dimethyl 5,7,12,14-tetraphenyl-6,13- dihydro-6,13-ethenopentacene-15,16- dicarboxylate (151). . . . . . . . . . . . . . . 99 viii Chapter 39. 5,7,12,14,-Tetrapheny1-6,lB-dihydro- 6,13-ethanopentacene-l5,16-dicarboxylic anhydride (153). PART II. ACID-CATALYZED AND PHOTOCHEMICAL REARRANGEMENTS OF NOVEL KETONES. INTRODUCTION. RESULTS AND DISCUSSION. A. Structure of the Bis-adduct Obtained From the Reaction of Hexamethyl-2,4-cyclohexa- dienone 9 and DABT-LTA. Acid-catalyzed Rearrangement of 1,3,3,4,7,8,10,12,12,13,16,17-Dodeca- methyl-benzo[1,2-e:4,5-e']bisbicyclo [2.2.2]oct-5,7-dien-2.ll-dione (154). Photoisomerization of 1,3,4,5,8,8,10, 11,12,14,17,17-Dodecamethyl-benzo [1,2-f:4,5-f']bisbicyclo[3.2.l]oct- 3,11-dien-2,14-dione (191). Photodecarbonylation of Syn-7,8-Syn- 16,17-Diepoxy-1,3,3,4,7,8,10,12,12,13, 16,17-dodecamethyl-benzo[1,2-e:4,5-e'] bisbicyclo[2.2.2]oct-2,11-dione (199). ix page . 100 .101 . 102 103 103 107 .120 124 Chapter Experimental. 1. 1,3,3,4,7,8,10,12,12,13,16,17-D0deca- methyl-benzo[1,2-e:4,5-e']bisbicyclo [2.2.2.]oct-7,16-dien-2,ll-dione (154). 2,4,5,6,6-Pentamethyl-3-methyl-d3- 2,4-cyclohexadienone (158). 2,4,6,6,-Tetramethyl-3,5-dimethy1-d6- 2,4-cyclohexadienone (159). 1,3,3,4,8,10,12,12,13,17-Decamethyl- 7,16-dimethyl-d6-benzo[1,2-e:4,5-e'] bisbicyclo[2.2.2]oct-7,16-dien-2,11- dione (160). 1,3,3,8,10,12,12,17-Octamethyl-4,7,13,16- tetramethyl-dlZ-benzo[1,2-e:4,5-e']bis- bicyclo[2.2.2]oct-7,16-dien-2,11-dione (161). Acid-catalyzed rearrangement of ketone 154. a. 1,5,6,7,8,8,10,11,12,14,17,17-D0deca- methyl-benzo[1,2-c:4,5-f']bisbicyclo [3.2.1]Oct-6,11-dien-2,13-dione (176). b. 1,5,6,7,8,8,10,11,11,13,16,17-Dodeca- methyl-benzo[1,2-c:4,5-e'Jbicyclo [3.2.1]oct-bicyclo[2.2.2]oct-6,16-dien- 2,12-dione (177). page 133 -133 .134 134 - 135 . 135 .136 . 136 137 Chapter page c. 1,5,6,7,8,8,10,11,12,13,17,17-Dodeca- methyl-benzo[1,2-c:4,5-c']bisbicyclo [3.2.1]oct-6,11-dien-2,14-dione (178). . . . 138 d. 1,3,4,5,8,8,10,11,12,14,17,17-D0deca- methyl-benzo[1,2-f:4,5-f']bisbicyclo [3.2.1]oct-3,11-dien-2,13-dione (179). . . . 138 7. 1,3,5,8,8,10,12,14,17,17-Decamethyl-4,11- dimethyl-da-benzo[1,2-f:4,5-f']bisbicyclo [3.2.1]oct-3,11-dien-2,13-dione (180). . . . . 139 8. 1,5,6,7,8,8,10,12,14,17,17-Undecamethy1- ll-methyl-d3-benzo[1,2-c:4,5-f']bisbicyclo [3.2.1]oct-6,11-dien-2,13-dione (181). . . . . 139 9. The equilibration of ketone 178 in TFA. . . . . .139 10. Photoisomerization of 1,3,4,5,8,8,10,11,12- 14,17,17,-dodecamethyl-benzo[1,2-f:4,5-f'] bisbicyclo[3.2.1]oct-3,11-dien-2,14-dione (179). . . . . . . . . . . . . . . . . . . . . . 140 11. Syn-7,8-syn-16,17-diepoxy-1,3,3,4,7,8,10,12, 12,13,16,17-dodecamethyl-benzo[1,2-e:4,5-e'] bisbicyclo[2.2.2]oct-2,11-dione (199). . . . . . 140 12. Syn-7,8-syn-16,17-diepoxy-1,3,3,4,8,10,12, 12,13,17-decamethyl-7,16-dimethyl-d6-benzo [1,2-e:4,5-e']bisbicyclo[2.2.2]oct-2,11- dione (200). . . . . . . . . . . . . . . . . . . 141 xi Chapter page 13. Syn-7,8-syn-16,17-diepoxy-1,3,3,8,10,12, 12,17-octamethyl-4,7,13,16-tetramethyl- d12-benzo[1,2-e:4,5-e']bisbicyclo[2.2.2] oct-2,11-dione (201). . . . . . . . . . . . . . 142 14. Photodecarbonylation of Syn-7,8-syn-16, 17-diepoxy-1,3,3,4,7,8,10,12,12,13,16, l7-dodecamethyl-benzo[1,2-e:4,5-e']bis- bicyclo[2.2.2]0ct-2,11-dione (199). . . . . . . 142 LIST OF REFERENCES. . . . . . . . . . . . . . . . . . . . 144 xii Table page LIST OF TABLES 1. Potential Diaryne Precursors. . . . . . . . . . . . . 21 2. Selected Examples of N-amination. . . . . . . . . . . 28 3. Adducts derived from Two Diaryne Equivalents with Various Dienes. . . . . . . . . . . . . . . . . 41 4. Adducts of DABT-LTA with Various Dienes with Functionalities. . . . . . . . . . . . . . . . . . . 52 5. Adducts of 1,2,3,4-tetraphenylcyclopentadienone with Various Benzyne Precursors. . . . . . . . . . . 61 6. Di-adducts of DABT-LTA with Various Dienes. . . . . . 68 7. 1H NMR Spectra of Diketones (154, 176-179). . . . . . 114 8. 13C NMR Spectra of Diketones (154, 176-179). . . . . 115 xiii Appendix page 1. 250 MHz 1H NMR of 1,5-Diamino-benzo[l,2-d:4,5-d'] bistriazole (DABT) (40). . . . . . . . . . . . . . . 152 2. 13c NMR of 1,5-Diamino-benzo[1,2-d:4,5-d'] bistriazole (DABT)(40). . . . . . . . . . . . . . . 153 3. 250 MHz in NMR of 1,7-Diamino-benzo[1,2-d:4,5-d'] bistriazole (41). . . . . . . . . . . . . . . . . . . 154 4. 13c NMR of 1,7-Diamino-benzo[1,2-d:4,5-d'] bistriazole (41). . . . . . . . . . . . . . . . . . 155 5. 250 MHz 1H NMR of 1,6-Diamino-benzo[1,2-d:4,5-d'] bistriazole (63). . . . . . . . . . . . . . . . . . 156 6. 13c NMR of 1,6-Diamino-benzo[l,2-d:4,5-d'] bistriazole (63). . . . . . . . . . . . . . . . . 157 7. 250 MHz 1H NMR of 1-Amino-benzo[1,2-d:4,5-d'] bistriazole (64). . . . . . . . . . . . . . . . . . 158 8. 13c NMR of 1-Amino-benzo[1,2-d:4,5-d'] bistriazole (64). . . . . . . . . . . . . . . . . . 159 9. 250 1H NMR of Tetraethyl 1,4,5,8-tetrahydro- anthracene-1,4:5,8-diendoxide-2,3,6,7- tetracarboxylate (87). . . . . . . . . . . . . . . 160 10. 250 MHz 1H NMR of Tetraethyl 1,4,5,8-tetra- methyl-1,4,5,8-tetrahydroanthracene-1,4:5,8- diendoxide-2,3,6,7,-tetracarboxylate (89). . . . . . 161 xiv 11. 12. 13. 14. 15. 16. 17. 18. 19. 250 MHz in NMR of Dimethyl 1,4,5,8-tetra- hydroanthracene-1,4:5,8-diendoxide-l,5- dicarboxylate (91). 250 MHz 1H NMR of Tetramethyl 3,4,7,8-tetra- pheny1-1,4,5,8-tetrahydroanthracene-l,4:5,8- diendoxide-l,2,5,6-tetracarboxylate (99). 250 MHz in NMR of 2,6-Dibromo-1,4,5,8- tetrahydroanthracene-l,4:5,8-dien- doxide (101). Page 162 163 164 250 MHz 1H NMR of Bis-[2-methy1-3-phenyl-2,3-dihydro] benzo[1,2-d:4,5-d']diisoxazole (107). 250 MHz 1H NMR of 1,3,3,4,7,8-Hexamethyl- 5,6-bis(Z,Z-cyanomethylene)-bicyclo[2.2.2] oct-7-en-2-one (116). 13c NMR of 1,3,3,4,7,8-Hexamethyl-5,6- bis(Z,Z-cyanomethylene)-bicyclo[2.2.2]oct- 7-en-2-one (116). 250 MHz in NMR of tetramethyl 2,3,6,7- tetraphenylanthracene-l,4,5,8-tetra- carboxylate (128). 250 MHz 13 NMR of 5,7,12,14-Tetraphenylpenta- cene (141). 250 MHz in NMR of Dimethyl 5,7,12,14-tetra- phenyl-6,13-dihydro-6,13-ethenopentacene-5,16- dicarboxylate (151). XV 165 166 167 168 169 170 20. 21. 22. 23. 24. 25. 26. 27. 250 MHz 1H NMR of 5,7,12,14-Tetraphenyl-6,13- dihydro-6,13-ethanopentacene-l5,16-di- carboxylic anhydride (153). 250 MHz 1H NMR of 1,3,3,4,7,8,10,12,12,13,16,17- Dodecamethyl-benzo[1,2-e:4,5-e']bisbicyclo [2.2.2]oct-7,16-dien-2,11-dione (154). 13c NMR of 1,3,3,4,7,8,10,12,12,13,16,17- Dodecamethyl-benzo[1,2-e:4,5-e']bisbicyclo [2.2.2]oct-7,16-dien-2,11-dione (154). 250 MHz in NMR of 1,3,3,4,8,10,12,12,13,17- Decamethyl-7,16-dimethy1-d6-benzo[1,2-e:4,5-e'] bisbicyclo[2.2.2]oct-7,16-dien-2,ll-dione (160). 250 MHz 1H NMR of 1,3,3,8,10,12,12,17-Octa- methyl-4,7,13,16-tetramethyl-d12-benzo [1,2-e:4,5-e']bisbicyclo[2.2.2]oct-7,16- dien-2,11-dione (161). 250 MHz 1H NMR of 1,5,6,7,8,8,10,11,12,14,17,17- Dodecamethyl-benzo[1,2-c:4,5-f']bisbicyclo [3.2.1]oct-6,11-dien-2,13-dione (176). 13c NMR of 1,5,6,7,8,8,10,11,12,14,17,17— Dodecamethyl-benzo[1,2-c:4,5-f']bisbicyclo [3.2.1]oct-6,11-dien-2,13-dione (176). 250 MNz 1H NMR of 1,5,6,7,8,8,10,11,12,13,17,17- Dodecamethyl-benzo[1,2-c:4,5-c']bisbicyclo[3.2.1] oct-6,11-dien-2,14-dione (178). xvi- page 171 172 173 -174 °175 ~176 '177 - 178 11. 12. 13. 14. 15. 16. 17. 18. 19. 250 MHz in NMR of Dimethyl 1,4,5,8-tetra- hydroanthracene-1,4:5,8-diendoxide-l,5- dicarboxylate (91). 250 MHz 1H NMR of Tetramethyl 3,4,7,8-tetra- phenyl-1,4,5,8-tetrahydroanthracene-1,4:5,8- diendoxide-1,2,5,6-tetracarboxylate (99). 250 MHz 1H NMR of 2,6-Dibromo-1,4,5,8- tetrahydroanthracene-l,4:5,8-dien- doxide (101). Page 162 163 164 250 MHz 1H NMR of Bis-[2-methyl-3-phenyl-2,3-dihydro] benzo[1,2-d:4,5-d']diisoxazole (107). 250 MHz in NMR of 1,3,3,4,7,8-Hexamethyl- 5,6-bis(Z,Z-cyanomethylene)-bicyclo[2.2.2] oct-7-en-2-one (116). 13c NMR of 1,3,3,4,7,8-Hexamethyl-5,6- bis(Z,Z-cyanomethylene)-bicyclo[2.2.2]oct- 7-en-2-one (116). 250 MHz 1H NMR of tetramethyl 2,3,6,7— tetraphenylanthracene-l,4,5,8-tetra- carboxylate (128). 250 MHz 1H NMR of 5,7,12,14-Tetraphenylpenta- cene (141). 250 MHz 1H NMR of Dimethyl 5,7,12,14-tetra- phenyl-6,13-dihydro-6,13-ethenopentacene-5,16- dicarboxylate (151). XV 165 166 167 168 169 170 20. 21. 22. 23. 24. 25. 26. 27. 250 MHz la NMR of 5,7,12,14-Tetraphenyl-6,13- dihydro-6,13-ethanopentacene-15,16-di- carboxylic anhydride (153). 250 MHz 1H NMR of 1,3,3,4,7,8,10,12,12,13,16,17- Dodecamethyl-benzo[1,2-ez4,5-e']bisbicyclo [2.2.2]oct-7,16-dien-2,11-dione (154). 13C NMR of 1,3,3,4,7,8,10,12,12,13,16,17- Dodecamethyl-benzo[1,2-e:4,5-e']bisbicyclo [2.2.2]oct-7,16-dien-2,11-dione (154). 250 MHz 1H NMR of 1,3,3,4,8,10,12,12,13,17- Decamethyl-7,16-dimethyl-d6-benzo[1,2-e:4,5-e'] bisbicyclo[2.2.2]oct-7,16-dien-2,11-dione (160). 250 MHz 1H NMR of 1,3,3,8,10,12,12,17-Octa- methyl-4,7,13,16-tetramethy1-d12-benzo [1,2-e:4,5-e']bisbicyclo[2.2.2]oct-7,16- dien-2,11-dione (161). 250 MHz 1H NMR of 1,5,6,7,8,8,10,11,12,14,17,17- Dodecamethyl-benzo[1,2-c:4,5-f']bisbicyclo [3.2.1]oct-6,11-dien-2,13-dione (176). 13c NMR of 1,5,6,7,8,8,10,11,12,14,17,17- Dodecamethyl-benzo[1,2-c:4,5-f']bisbicyclo [3.2.1]oct-6,11-dien-2,13-dione (176). 250 MNz 1H NMR of 1,5,6,7,8,8,10,11,12,13,17,17- Dodecamethyl-benzo[1,2-c:4,5-c']bisbicyclo[3.2.1] oct-6,11-dien-2,14-dione (178). xvi° page 171 172 173 ~174 -175 -176 '177 ° 178 28. 29. 30. 31. 32. 33. 34. 35. 36. 37. 38. 39. 13c NMR of 1,5,6,7,8,8,10,11,12,13,17,17- Dodecamethyl-benzo[1,2-c:4,5-c']bisbicyclo [3.2.1]oct-6,11-dien-2,14-dione (178). 250 MHz in NMR l,3,4,5,8,8,10,11,12,14,17,17- Dodecamethyl-benzo[1,2-f:4,5-f']bisbicyclo [3.2.1]oct-3,11-dien-2,13-dione (179). 13c NMR 1,3,4,5,8,8,10,11,12,14,17,17-Dodeca- methyl-benzo[1,2-f:4,5-f']bisbicyclo[3.2.l] oct-3,11-dien-2,13-dione (179). 250 MHz in NMR of ketone 189. 13C 250 130 250 250 250 250 250 NMR MHz NMR MHz MHz MHz MHz MHz of 1H ketone 189. NMR of epoxy ketone 199. epoxy ketone 199. NMR of epoxy ketone 200. NMR of epoxy ketone 201. NMR of epoxide 202. NMR of epoxide 203. NMR of epoxide 204. xvii page 179 180 181 182 183 184 185 186 187 188 189 190 PART I. SYNTHESIS OF A NEW DI-ARYNE EQUIVALENT AND ITS APPLICATION TO ORGANIC SYNTHESIS 2 Introduction This thesis deals with the preparation and chemistry of arynes. In particular, it concerns the chemistry of compounds capable of producing twoaryne units on the same aromatic ring. Hence it is pertinent, in this introduction, to briefly review some of the history of aryne chemistry, the main literature methods for preparing arynes, and some of their chemistry, particularly their cycloaddition reactions. ' The term benzyne1 denotes ortho-benzyne, also' known as 1,2-dehydrobenzene or in Chemical Abstrggtg 1,3-cyclohexadien-5-yne. The last name a is somewhat misleading, since benzyne differs from benzene in having two less hydrogens but not in the stabilization associated with delocalization of double bonds.2 It is commonly represented by any of the structures 1-3. 2 Note that the electrons in the so-called triple bond are in orbitals which to a first approximation are orthogonal to the aromatic electrons, and also that the orbitals are canted and not parallel, thus decreasing the overlap from what is present in an ordinary triple bond; hence the increased reactivity of benzyne relative to ordinary alkynes. 3 Since 1902 there have been suggestions that benzynes might be intermediates in various aromatic substitution reactions.3 Wittig was the first to put the suggestion clearly and convincingly during the 1940's.4 He studied the reaction of halobenzenes withg phenyllithium. and found that 'biphenyl was formed, but that its ratet of formation from fluorobenzene was greater than from the other halobenzenes. A direct displacement of fluoride by the phenyl anion was therefore unlikely. Wittig suggested that the inductive effect of the fluorine facilitated removal of the o-hydrogen and -its replacement by lithium. Thus an o-fluorophenyl anion was generated, which then lost fluoride to give benzyne. Phenyllithium could then react rapidly with the benzyne to give o-lithiobiphenyl, which Wittig showed to be the primary product of the reaction. ‘2 ——' (*9 .' lPhLI O Q Li In this reaction phenyllithium has a dual role: it acts as a strong base to remove the o-hydrogen, generating the o-fluorophenyl anion, and it acts as a nucleophile in its addition to benzyne. In 1953, J. D. Roberts established the presence of arynes in reactions of 1-C14 chlorobenzene ‘with. potassium amide in liquid ammonia.5 The product consisted of aniline, half of which was labeled in the. 1-position and half in the 2-position. A mechanism which can explain all the observations involves elimination followed by addition: .. NH, * I KNH T N... (50%) liq IHFQ Xx NH, (5096) Observations of the UV absorption attributable to benzyne in the vapor phase,6 evidence from time-resolved mass spectrometry,7 and more recently of the IR spectrum of benzyne in an argon matrix at very low temperatures8 leave no doubt as to the existence of benzyne as a discrete molecular species. There is .now a very extensive chemistry of ortho-benzyne and of some of its substituted derivatives (arynes), but much less is known of meta-9 and para-benzyne10 isomers. A variety of methods are described in the literature for the preparation of benzyne. However they all fall into two categories. One common way to generate benzyne is to 5 remove two adjacent substituents from an aromatic nucleus. Another useful general route to benzyne is the fragmentation of heterocyclic rings fused to the ortho positions of the aromatic system. Some of the different conditions that can be used to generate benzyne are Shown below: N; N \ \N N/ co, ”‘0‘” | NH, 613 \ OI ./ \ o ' 02‘?" 512 714 Probably the most convenient method involves thermal decomposition of the product 4 of diazotization of anthranilic acid.11 Both substituents are excellent leaving groups, one leaving with an electron pair, the other leaving without. When 4 decomposes in the presence of an added nucleophile, the benzyne intermediate is trapped by the nuclophile as it is. formed. If a conjugated diene 8 or a‘ dienone 9 is present, benzyne will react with it to give [4 + 2] cycloadduct, 10 or 11, respectively. In the absence of 6 other compounds with which it can react, benzyne will undergo [2 + 2] cycloaddition to itself to give biphenylene 12. 1217 Another route to benzynes involves organometallic compounds derived from aryl halides.12 An example is the generation of benzyne from 1-bromo-2-fluorobenzene 5 with magnesium in tetrahydrofuran. If the temperature is kept near 0°C, 2-fluorophenylmagnesium bromide is formed. At higher temperatures, magnesium halide is eliminated and benzyne results. With cyclopentadiene, the [4 + 2] cyclo- adduct 13 was obtained in 66% yield.12 However, in this Z, .3... (1.23:1 it 13 (86%) reaction, the diene may not contain carbonyl or 'similar groups that are reactive toward the Grignard reagent. In fact, the synthetic utility of benzyne reaction depends in large part on the success with which the benzyne can be generated by one reagent, but trapped by another. Oxidation of 1-aminobenzotriazole with lead tetraacetate also servesas a source of benzyne under mild conditions.18 An oxidized intermediate (nitrene) decomposes with loss oftwo molecules of nitrogen: u ' ”uh- p \ -2N2 O \\N Moxie), O'\ \N I / 6 7 Wm o NM2 L N' _ 6 Ph 0 Ph Ph 14 Ph Ph QC Ph Ph Ph 15 (95%) 8 When the oxidation was carried out in the presence of tetraphenylcyclopentadienone 14, 1,2,3,4-tetraphenylnaphtha- lene 15 was obtained in high yield.18 Another heterocycle that can serve as a benzyne precursor is benzothiadiazole-l,1-dioxide.14' With selected dienes, \ Oh / N\ I (54%) ./" é’ /‘\ O 0 +50, 7 +N2 / ‘O (36%) moderate yields of cycloadducts were obtained. The prepara- tion of this benzyne precursor is lengthy and the compound explodes at about 60°C, but it decomposes slowly at about 10°C to give benzyne, nitrogen, and sulfur dioxide. Reactions of benzyne have been used to synthesize compounds that ‘were otherwise difficultly accessible. For example, intramolecular additions to aryne intermediates 16 from 1-(2-bromobenzy1)- or 1-(3-bromobenzyl)-1,2,3,4-tetra- hydroisoquinoline derivatives are the basis of some elegant syntheses of natural products.19 In Scheme 1, paths a, b, and c define cyclizations through 2-, 4a and 8-positions Scheme 1 cup I40 C ‘CH; , 19 R 17 11,3 :ocu,o 18 52,3 =ocn-I,o 19 R,R’-7-ocn,o R—R—OCH', R=R=ocfl R=OCH,,R=H R= ocu,,R”=H 10 of the isoquinoline moiety, leading to dibenzoindolizines 17, morphinandienones 18, and aporphines 19, respectively. Bis-arynes such as 20 and 21 could be useful synthetic precursors to polysubstituted arenes or other novel structures.20 However, very few. bis-aryne equivalents, or precursors of bis-arynes,20'21 are known. Bis-arynes have been postulated in certain mass spectral fragmentations R R R l I /’ R 20 21 and to rationalize products from the copyrolyses of benzene with pyromellitic or mellophanic anhydrides.22 o o F _O - ./ A \ o o—-> I.I——> 'l J \ V / ‘0 ‘0 ‘ l-w. These reactions may not really involve a bis-aryne, however, since they could occur in a stepwise fashion. Compound 23 was synthesized, albeit in very low yield, via bis-aryne equivalent 22 by treatment with strong base.Zla 11 t-Bu Br _ K' t- + BuO % 26h Br t-Bu 22 t-Bu 23 (2%) The reaction of furan with benzyne, discovered by Wittig and Harle,23 was the earliest example of benzyne behaving as a dienophile. In a possible extension of this reaction to bis-arynes, Wittig found that with magnesium in tetrahydrofuran 24 gave mainly mono-adduct 25 (34%) and only 5% of the bis-adduct 26. With butyllithium in place of magnesium, a 15% yield of bis-adduct and no mono-adduct was obtained. CH, 3' Bf Mg . O + a - 'TIIF F F CH, 24 25’ (34%) 12 The bis-epoxide 28 ‘was synthesized in 36% yield via a di-aryne equivalent 27 by Guiles and coworkers.24 The reaction was carried out in two steps, however, since addition of the second furan molecule required a higher temperature than that of the first. Hart and coworkers have developed a much improved method ofpgenerating arynes from diaryne equivalents,20b and have improved the synthetic utility of these reactions. For example: R R Br Br ~\‘ + O «'BuLi / Br Br R . R OCH, OCH, (72 as) 13 Recently, bis-annulation of naphthalene via a 1,5-naphthodiyne synthon 29 was reported by Gribble and LeHoullier.210 0Tb Br . . x Br X OT! 29 x , PhLi fi” ‘ X X X X==Hl30%l x .,, x F|4axn N... X \\ m-CPBA CHCQ X X==IL F X===Hl853fl Fl75%l Wege and Stringer reported the preparation of some novel furan derivatives related to triphenylene (31 and 33) by a strategy involving sequential Diels-Alder additions of arynes to furan. However, the yields (30 and 32) in the key steps are low.21b 15 Much of the work in this area has been done in recent years in this laboratory. Hart and coworkers described the use of tetrahalobenzenes as di-aryne equivalents. When treated with two equivalents of an organolithium reagent in the presence of certain dienes, they readily form bis-cycloadducts. With these reagents benzenes could be converted to anthracenes or phenanthrenes in just two steps.20 For example, decamethylanthracene was prepared. in overall 54% yield.20b The para di-benzyne equivalent tetrabromo-p-xylene reacts with n-butyllithium in the presence of N-substituted pyrroles to give bis-adducts. Removal of nitrogen bridges then gives the anthracene: 8 Br. / . + II ll/. «BuLI \- TOLUNE B Br ° -78 C (5420 16 This methodology was applied to a phenanthrene synthesis: :jw-N lac Br ” O 8 L. a or u I H": 3' Toluene I “78°C Vacuum» . Hart and coworkers have developed a simple one-step synthesis of pentiptycene20d using diaryne equivalents.20d A toluene solution of anthracene and tetrabromoarene, when treated with n-butyllithium in hexane around -10°C gave pentiptycene 32 in high yield. Toluene I 3 Br fi'BULi Toluene n-BuLl -1o°c 17 Pentiptycene 34 had been prepared previously, but in low yield (10%) by Russian workers.25 The required fluorobromotriptycene 35 had to be synthesized from anthra- cene in four steps, so that the overall yield from readily available starting material was quite low. 50 Z. . 1.1.4.... 0 .. Heptiptycene 38 was synthesized using a 2,3:6,7-anthradiyne equivalent 36 in three steps via a pentiptycene intermediate 3721d. 18 1,2,4,5- and 1,2,3,4-Tetrahaloarenes are versatile synthetic equivalents of 1,4- and 1,3-diarynes (20 and 21 respectively). One -synthetic limitation of this method, however, is that the receptor diene may not contain functionality which will compete with the tetrahaloarene for the organolithium reagent. In practice this means that the diene usually must not contain carbonyl, halogen, or similar groups. Therefore it seemed worthwhile to pursue alternative ways of generating bis-benzynes to circumvent this problem. One obvious type of diaryne precursor would be the bis-diazonium carboxylates derived from appropriate diamino tere- or isophthalic acids (analogous to the 19 anthranilic acid route to arynes). We synthesiz- ed 2,5-diamino-1,4-benzenedicarboxylic acid by a modified literature procedure. So far, however, attempts to tet‘razotize this bis-anthranilic acid have failed. We also synthesized 1,5- and 1,7-diamino-benzo[1,2-d:4,5-d']bistri- azole (DABT) 40 and 41 from the known precursor 39.26 In our attempt to explore the scope of this bis-annulation technique, a variety of dienes and a 1,3-dipole (nitrone) NFl l‘ ,3, ’ N N N \ KOH / \\ er ‘\N ’1’ N“ N \N '/ H,N-OSO,H \ 'r/ H 40 "“2 39 + N / \ N/’ \‘N \\ N” l l NH, NH, 41 were used. Bromofuran, esters, dienones and nitrones, all of which are presumably incompatible with the butyllithium used to generate arynes from tetrahaloarenes gave bis-adducts in good yields. It is the purpose of this part of the thesis to describe the synthesis and synthetic applications of these new diaryne precursors. 20 Results and Discussion A. Synthesis of Diamino-benzo[1,2-d:4,5-d']bistr1azole (DABT), A New Useful 1,4-dibenzyne Equivalent. This investigation was directed toward the synthesis of the synthetic equivalent of a reactive intermediate, dibenzyne 20. The problem could be approached by the prepara- tion of an appropriate group of dibenzyne precursors, 20 and an examination of the reactivity of these compounds with members of representative classes of dienes. .The follow- ing dibenzyne precursors were chosen as worthy of study; they appeared to offer the most promising routes to arynes (Table 1). The first study began with the synthesis of 1,4-diamino- terephthalic acid, 42, that contains the anthranilic acid grouping twice. Several syntheses of 42 are reported in literature.27:28 One method involved the preparation of 42 from its corresponding diester 44, via diethyl 2,5-diamino-1,4-dihydroterephthalate 43. Aromatization of 43 by action of iodine28 according to Eremeeva and coworkers (always gave product which was contaminated with iodine. Purification of the product. was quite troublesome and therefore it was desirable to improve the preparation of 44. When compound 43 was refluxed in xylene in the presence of a catalytic amount of palladium on charcoal, the aromatic 21 Table 1. Potential Diaryne precursors Precursor Method of Generation H2" CO,H Thermal decomposition after diazotization HO,C NH, 42 l": N /" S N N l 40 ""2 Oxidative nitrogen extrusion N N . / \ N/' ‘\N \l' ”l/ compound 44 was obtained in 90% yield. Purification from ethanol afforded orange needles which had the same melting point as in the literature.28 22 ll ‘.N.OEU (:0 Et EIOH 2 Cazfit E (':H,CO t :5 NH,OAc d, cmcou 241250. ll EtO,C EtO,C 43 (95 96) o (63%) NH: Pd/C XyIOI‘. A NH, NH, co H 1- 0a. NeOH/ 2 EtOH com 2. H 0’ "02¢ ’ EtO,C H, NH 42 (89%) 2 44(90%) The diaminoterephthalic acid 42 was readily prepared by hydrolysis of 44. However, an immediate problem arose with its solubility. The compound is practically insoluble in most organic solvents, as reported in the literature.27 In fact, compound 42 is even insoluble in hot dimethylsulfox- ide. All attempts to tetrazotize 42 were unsuccessful. Some efforts were also made to prepare the corresponding mono-acid with the hope that it might serve as a diaryne equivalent in a stepwise manner. Saponification of 44 with one equivalent of sodium hydroxide, followed by acidification gave only the starting ester. At this point this approach to a diaryne equivalent was abandoned in favor of another approach. 23 The next goal was the synthesis of 1,5-diamino-benzo[1,- 2-d:4,5-d']bistriazole 40 which is analogous to 1-aminobenzo-. triazole, 6. Compound 6 had previously been prepared by two routes, either diazotization of a suitably protected o-aminoarylhydrazine 45 followed by removal of the protecting group of 46 (Scheme 2) or by direct amination of the parent triazole 47 (Scheme 3).18 As can be seen, the former method requires more steps but it provides only the desired product Scheme 2 No 21.|"|ONO”zp¢|/c NH: 2.H,C(C0:Et)z NH (cogul , H—N=C(co,£u, 45 HONO N\\N HCl . \\N 3’ I/ ' / N=ccco,£u, NH, 46 6 Scheme 3 N NH, so H N \\ o ’ > \\N + / \ —NH, ~ 2* N/ ./ L NH, 47 6 (38 96) 48 (11 96) 24 in high yield (over 54%) whereas the latter method gives a mixture of 1- and 2-‘-isomers in good yield (49%) . But in the case of diamino-benzo[1,2-d:4,5-d' ]bistriazole 40 (DABT) the direct amination method appeared more promising o, No. H,N NH: H ONO » , H,N NH, ' ‘N, Nz’ 49 50 o,N No, (Eto,c),c=N-HN NH-N=C (co,Et), because difficulties were encountered in the preparation of the required tetrazotized' intermediate 50 from the corresponding diamino compound 49. Also the desired DABT could be prepared in a single-stage synthesis by amina- tion of the known benzo[1,2-d:4,5-d']bistriazole 39 (Scheme 4)29v30 with an apprOpriate aminating agent. Several attempts to repeat the literature procedure for the preparation of 39 always gave low yields in some steps (steps 4 and 5, yields (3%). The literature procedure has been improved as described here and each step now works well. Compound 39 can be prepared in good yield (overall 54%) 'by a six-step process starting from m-dichlorobenzene. The most important improvement involves the conversion of 1,5-bis[acetylamino]-2,4-dinitrobenzene 51 to 1,7-diacetyl- 25 Scheme 4 KNo, NH,(9) ———-> ———> H,so, . O O, O 0 Sta 1 2 p (71%) 5“" 2 49 (95%) H, .. 1 HM HAc NHAc A420 A‘ O Pd/c “H 0 ———> ———> P 0 02 b H2 H2 .1 S 51 (so 94) “p ‘ 52 'I‘ NaNO /N N\\ c . H o N _____2_> N/ / at ,S 5 N/ \\N HCI \N 50% EtOH/ \\ M/ o N Step 5 Ac -c H 53 (93%) 39 (96 95) 26 benzo[1,2-d:4,5-d']bistriazole 53 where the yield has been improved from a reported 60% to 93%. The major differences from the literature procedure are as follows: 1. hydrogena- tion of 51 in ethanol instead of acetic acid using a weight ratio of 4:1 1,5-bis[acetylaminio]2,4-dinitrobenzene 51: 10% palladium on charcoal. For example, when the compound 51 (12 g, 0.0425 mol) was hydrogenated in ethanol (150 mL) over 10% palladium on charcoal (1 g) under 60 psi for 72 h, only partial reduction was observed. However, when 3 g of 10% palladium on charcoal was used under otherwise similar conditions, the reduction was complete in 3 h. The catalyst used in the reduction was recovered and recycled. 2. The diazotization of compound 52 was accomplished in H20 at 0°C instead of in acetic acid at 25°C. Many nitrogen heterocycles can be aminated on nitrogen using various aminating agents such as hydroxylamine-O-sulfonic acid 54,31 0-sulfony1 55,32 O-actyl- 5633 and O-nitro- phenylhydroxyl amines 57.34 These amines can be represented ii I O 54 55 O ‘ u y H,N-O-C H,N—CFO: 56 oz 57 27 by the general structure, NHz-X, where X is a good leaving group. The procedure involves removal of the acidic proton of the heteroaromatic compounds using' an appropriate base, followed by nucleophilic displacement on the amino group. Among the reagents listed above, hydroxylamine-O-sulfonic acid is the most easily accessible and is known to aminate Ba 5e \ NH,—X N—H *4 N 5' \ \ / / / N_NH1 benzotriazole 4718 and other analogous systems.31 For example, N-amination of benzotriazole was reported by Campbell and Rees, who treated 47 in aqueous potassium hydroxide solution at 70-75°C with hydroxylamine-O-sulfonicv acid 54 to give 1-aminobenzotriazole 6 and 2-aminobenzotriazole 48. The yields of pure» material obtained. after chromatography 'were 38 and 11%, respectively. Also, the starting benzotria- zole ‘was recovered (32%) after acidification of the ‘basic solution followed by ether extraction. 0-(2,4-Dinitrophenyl)-hydroxylamine 57 and O-mesitylene- sulfonylhydroxylamine 55 are also reported to aminate triazole systems. For example, reaction of 1H-cycloheptatriazole-6-one 58 with 57 afforded 1-aminocycloheptatrizole-6-one 59 and 28 N . \\N+57 ——>o \N'0 l/” "H’ / / \N N l NH, 59 . 60 58 the 2-amino-2H isomer 60 in a ratio of 1.7:1 in 75% yield.35 It is important to notice that amination of the triazole system, regardless of the reagent employed, always provided a mixture of 1- and 2-amino isomers. Some selected examples of N-amination with 0-substituted hydroxylamines are summarized in Table 2. Table 2. Selected Examples of N-amination Aromatic Nitrogen Compound Hydroxylamine Yield Reference (2) 0 II - § N Na 57 88 34 II 0’ Ph Ph Ph / \ P11 56 37 36 N- Na’ Although not an amination reaction, treatment of 39 with picryl fluoride belongs to this type of reaction. Thus the reaction of 39 with two equivalents of picryl fluoride gave a mixture of two dipicryl derivatives, which was resolved by extraction with hot acetone to give 1,5- and 29 1,7-dipicrylbenzo[1,2-d:4,5-d']bistriazole (61 and 62) in 56 and 44% yield, respectively.37 This reaction encouraged me to try the amination reaction. Pk il. 2 equiv ' - N /N N‘\~ "F N/flI N‘\N + N//N \\N N\\N / on F \\N N/ \lil T/ l I H pk Pk Pk 39 61 (56 96) 62 (44 %) pk = 2,4,o,—trl—nltr0phenyl Reaction of benzo[1,2-d:4,5-d']bistriazole 39 in aqueous potassium hydroxide solution at 66-68°C with hydroxyl- amine-O-sulfonic acid 54 gave the di-aminated products as a mixture of 1,5-, 1,7- and 1,6-isomers (40, 41 and 63) and two mono-aminated products (64 and 65) in 45 and 48% yields, respectively. No other products were detected from the reaction mixture. The ratio of isomers 40, 41 and 63 was determined to be 53:12:35 by integrating the peaks at 6 8.24 (1,5-isomer), 8.69, 7.71 (1,7-isomer) and 8.59, 7.96 (1,6-isomer) in the 250 MHz 1H NMR spectrum. The recover- ed mono-aminated compounds were recycled for further amination using the same reaction conditions. The three isomers were separated in excellent purity by fractional recrystallization from ethanol taking advantage of their different solubilities. The 1,6-isomer is very soluble in hot ethanol and the 1,5-isomer is less soluble than'the 1,7-isomer. The structures of 40, 41 and 63 were assigned mainly from their spectral data. Compound 40, mp 292°C (dec) gave excellent analytical values in agreement 30 N ' N\ O N/ U \N + H,N-o-g-OH KOH/H’O \\N T g 39 H H: N A \/\ + N)" \ \\N \N A / 40 H2 'Lflz NH: 41 T“ x" / + H \\ \N/ _N z 63 /I \ \ J: / + | + —NH, '\\N / INN \N/ NH, 65 31 with formula, C6H6N8 and its mass spectrum showed a parent peak at m/_e_ 190 (intensity 16), a fragmentation peak at m/g 162 (Iv-nitrogen) and a base peak at 111/; 105. The 250 MHz 1H NMR spectrum consisted of two signals at 5 8.24 and 7.18 for the aromatic and amine protons, respectively. A single peak for the aromatic protons is only consistent with the symmetry of the 1,5-isomer. The 13C NMR spectrum of 40 showed only three signals as required by symmetry, at 5144.16, 131.40 and 97.43. The infrared spectrum showed strong primary amine absorptions at 3386 and 3610 cm'l. The in NMR (250 MHz) spectrum of 41, mp 263°C, showed two equal doublets at 5 8.69 and 7.71 for the aromatic C4- and C3-protons which were mutually coupled (i = 1 Hz), whereas at 5 7.09 there was a sharp singlet for the amine protons. The 13C NMR spectrum showed four peaks at 5 142.93, 133.32, 108.42 and 87.43, consistent with the C2v symmetry of 41. The ‘unsymmetrical diamine structure 63 ‘was clear from its spectra. Thus 63, mp 271-273°C, showed six peaks in its 130 NMR spectrum at 5 143.36, 139.98, 138.87, 132.72, 104.63 and 91.08. The 250 MHz 1H NMR consisted of two equal aromatic doublets at 58.59 (C4-H, A = 1 Hz) and 7.96 (Cg-H, g,= 1 Hz) and a singlet at: 57309 for the amine protons. It was noticed that two signals (~ 5100) with higher intensity than the others in each 13C spectrum of the three isomers are notably shifted to higher field than normal aroma- tic region. On the basis of intensity, the shifted bands were suspected to be due to those carbons with hydrogen substi- 32 tuents. It was thought that a 13C off-resonance coupling NMR experiment might confirm this assignment because each shifted carbon band would be split into two by the adjacent hydrogen. The coupled 13C spectrum of 40 had four bands at 5 144.38 (1 = 1 Hz), 131.65 (._I_ = 1 Hz), 99.13 and 96.37 confirming that the band at 597.43 (decoupled) was responsible for the carbon with a hydrogen substituent. The coupled 13C spectrum of 41, with six signals at 5142.92 (4 = 1 Hz), 133.26 (g = 1 Hz), 109,78, 107.07, 88.83 and 86.04 also proved that the relatively high field bands are due to the carbons with hydrogen substituents. The ratio of the recovered mono-amines 64 and 65 was determined to be 79:21 by integrating the peaks at 58.10 (d, i = 1 Hz), 7.65 (d, ,1 = 1 Hz) and 7.99 (s) in the 250 MHz 1H NMR spectrum. The mono-amine 64 was isolated in ‘pure form by recrystallization from ethanol. The melting point of 64 is much higher 0 400°C) than those of the diamino compounds, probably due to a dipolar ion structure 66 since the amine contains both an acidic proton and a basic amine in the same molecule. The 1H NMR (250 MHz) spectrum of 64 had two equal doublets for the aromatic protons at 58.10 (,1 = 1 Hz) and 7.65 (,1 = 1 Hz) and a singlet at 5 6.83 for the amine protons. The 13C NMR spectrum showed the expected six peaks at 5 146.19, 144.96, 142.18, 130.54, 101.60 and 90.66. 33 /.-" "\\ “N7 /"l N 'r 66 ’ N ”3 Compound 65 was not isolated pure, but was always contaminated with 64. The mono-amines (64 and 65), unlike the diamino compounds (40, 41 and 63), did not readily separate on being warmed in ethanol (i.e., during recrystallization). The structure of 65 was deduced by comparing the 1H NMR spec- trum of 64 with that of the mixture of recovered mono-aminated compounds. The singlet at 5 7.99 was thought to be due to the structure 67 (dipolar ion form of 65). . N\ . “€- / /N--NH, .N \N 67 Amination of 39 with 0-(2,4-dinitrophenyl)hydroxylamine 57 was capricious and gave no better yield and more difficult workup than with hydroxylamine-O-sulfonic acid. B. Use of a New Diaryne Equivalent, (DABT).in Bis-annulation. The bis-annulation of tetrahalobenzenes with various classes of dienes including furans, pyrroles and cyclopentadi- enes with no other functionalities is now well established.20 However, similar annulation with dienes which contain carbonyl or similar groups, or with 1,3-dipoles, has not been possible with these or other diaryne precursors. This work represents 34 the first study of those dienes or of a 1,3-dipole with the new di-aryne equivalent 1,5-diaminobenzo[1,2-d:4,5-d']-bis- triazole (DABT) 40, using lead tetraacetate (LTA) as the oxidizing agent to generate an aryne. The initial study began with the development of an oxidation method for DABT 40. Generation of benzyne from 1-aminobenzotriazole was reported by Campbell and Rees and their general procedure was as follows:18 1-aminobenzotria- zole 6 was dissolved in a dry solvent such as benzene, methyl- ene chloride, toluene, acetic anhydride or carbon tetrachlo- ride and this solution was added dropwise to a stirred suspen- ”\ ii i T > ° PbCOCCH3),——) .' ° PbCO CH,),+N, hi 6 NH, I 1 sion of lead tetraacetate in the same dry solvent at room temperature. 'The reaction was always instantaneous (evolution of N2). Work-up involved filtration, evaporation of the solvent, and chromatography of the residue. The reaction pathway involves oxidative removal of the amino hydrogens from 1-aminobenzotriazole 6, producing' a nitrene» 68, 'which might be expected to fragment to benzyne 1 and two molecules of nitrogen. This framentation process could occur by a concerted process, or by a radical mechanism, or by nitrene insertion to give benzotetrazine 69, followed by decomposi- tion; or by ring Opening of 69 to produce a dipolar species 70, which could lose two nitrogen molecules. 35 ~\ ~\ 9“» ME): I N 1 f N N; 69 70 In terms of solubility, DABT is markedly different from 1-aminobenzotriazole. DABT is almost insoluble in common organic solvents such as benzene, chloroform or toluene in which 1-aminobenzotriazole is soluble, However, DABT is very slightly soluble in tetrahydrofuran (THF) at room temperature (ca. 3 mg in 100 mL). Several attempts to adapt the above method to the oxidation of DABT met with no success. For example, when DABT suspended in THF was added to a stirred suspension of lead tetraacetate in the same solvent at room temperature (or at reflux) over 1 h, no reaction took place (no evolution of N2) and the unreacted DABT was recovered quantitatively. With several other solvents, e.g., benzene, toluene, ether or dimethyl sulfoxide, similar results *were obtained. However, it was suspected that the reaction might occur by using inverse addition, since the oxidation of 1-aminoben- zotriazole with LTA is very fast. Therefore, even a small amount of DABT dissolved in THF may initiate the reaction. 36 Indeed, when LTA suspended in THF was added to a stirred suspension of DABT in the same solvent at room temperature, nitrogen evolution was almost instantaneous and ceased on completion of addition of LTA. Apparently, reaction between LTA and the DABT dissolved in THF increased the further solubility of DABT driving the equilibrium to the right. However ether, methylene chloride and toluene proved to be unsuitable solvents for the reaction due to an even lower solubility of DABT in those solvents. Throughout 'the course of this bis-annulation study, only THF was used as the reac- tion medium. The failure of the reaction when DABT was added to the LTA suspended in THF is probably due to insolubil- ity of DABT. To test the utility of DABT-LTA, simple furans were chosen aS-the dienes. The following is a general oxidation procedure for the use of DABT as a diaryne equivalent. To a mixture of 2 mmol of diene and 1 mmol of DABT in 100 mL of dry THF at room temperature was added in portions 2.2 mmol of LTA over a period of 30 min. After 10 min. additional stirring, the lead diacetate was filtered, and the filtrate was usually worked up by extraction of the adduct into methylene chloride and purification by chromatography and/or recrystallization. Reaction of 1,5-diamino[1,2-d:4,5-d']bistriazole (DABT) 40 with furan 8 and lead tetraacetate (LTA) gave the first bis-annulation example 71 derived from DABT, in 79% yield as a mixture of two stereoisomers. The ratio was determined 37 to be 77:23 by integrating the peaks at 6 7.20 and 7.19 for the aromatic hydrogens in the 250 MHz 1H NMR spectrum. The 13c NMR spectrum showed six bands indicating a mixture of two isomers. When the sequence was repeated with excess furan (ten fold), a similar yield. (80%) was obtained. With 2,5-dimethylfuran 72, the bis-adduct 73 was obtained in 81% yield. The 250 MHz 1H NMR spectrum had five singlets at 6.96, 6.78 (minor), 6.76 (major), 1.87 (major) and 1.86 (minor) indicating a mixture of two isomers in a rati0~ of 19:81 integrating the peaks at £56.78 and 6.76. The 13C NMR spectrum showed seven peaks confirming the presence of two isomers. NH, R R R \ LTA " 2 eQuiv. O 0 (:1/ THF RT ' R 0.511 R R 8 R = H 71 R=H(79%) (77:23) 72 R=CH, 73 R=CH,(81%) (81:19) Treatment of 1,7-diamino-benzo[1,2-d:4,5-d']bistriazole 41 with 2,5-dimethylfuran and LTA also afforded 73 as a mixture of two stereoisomers, in 80% yield in the same ratio as observed before, 19:81. 113(1)? 9‘1"“. 41 38 The oxygen bridges of 73 were easily removed in overall 83% yield to give l,4,5,8-tetramethylanthracene 7538 by catalytic hydrogenation of 73, followed by dehydration of the resulting 74. 3 H, HCI Pd? C EtOH Et OH The yields in these bis-annulations were quite satisfac- tory compared to other analogous examples. For example, oxidation of 1-aminobenzotriazole and LTA in furan gave, on distillation, 1,4-epoxy-1,4-dihydronaphthalene 10 in 80% N\\ \ L 1' A /" ’ ° a ‘m / . N l N yield.18 6 H, . 1o (80%) Hart and coworkers prepared similar bis-adducts (77 and 78) using tetrabromo-p-xylene 76 as a diaryne precur- sor.20b Treatment of 76 and furan 8 with n-butyllithium gave the diadduct 77 in 77% yield as a mixture of two isomers in a ratio of 53:47. When the sequence was repeated with 2,5-dimethylfuran 72, the diadduct 78 ‘was obtained in 78% yield as a mixture of two isomers, but in a slightly higher ratio (57:43). It is noteworthy that DABT with both dienes provided a higher stereoselectivity than did tetrabromo-p-xyl- 39 ene 76, and between the two dienes 2,5-dimethylfuran gave a better stereoselectivity. 3*: + (2 + » how 8 R =H 77 R = H (77%)(53:47) 72 R =CH, 78 R = CH,(78%)(57:43) . In order to explore the generality of the bis-annulation technique with 40, different classes of dienes were employed. Treatment of 40 with 1,3,4-trimethyl-2,5-diphenylpyrrole 79 and LTA gave the diadduct 80, mp, 273-275°C identified from its analytical and spectral properties. The 250 MHz 1H NMR spectrum of 80 consisted of aromatic multiplets Ph p1. Ph \ PblOAc), 40 + --N —> / Ph ' Ph Ph 79 ' so (77%) (5 7.6-7.2, 22 H) and two broad singlets (51.8, 12 H and 1.6, 6B). The 13C NMR spectrum had ten major peaks as required by a single isomer with appropriate chemical shifts. Similarly, diadduct 81 was prepared in 57% yield from the reaction of tetrabromo-p-xylene 76 and 79 with n-butyllithium as a mixture of two isomers (ratio not known).39 40 Ph Ph Ph ‘\. "'BuLi 76 4- --N ““_‘—“*’ / Ph Ph Ph 79 81 Similar treatment of 40 *with 2,3-bis-(methylene)-bi— cyclo[2.2.1]heptane 8240 afforded the bis-adduct 83 in 93% yield. The 250 MHz 1H NMR indicated a mixture of two isomers in a ratio of 91/9 integrating the two small equal singlets (syn) at 5'7.56 and 7.43 and one large singlet (anti) at 56.96. j) _.._. «.004 Apparently, more substituted dienes gave the higher stereo- selectivity regardless of precursors and the results are summarized in Table 3. Examples of benzyne cycloadditions to dienes containing carbonyl functionality are rarely found in the literature. Benzyne, generated by thermal decomposition of 152,3-benzo- thiadiazole-1,1-dioxide ‘7 added. U3 methyl cyclopentadien- yl-l-carboxylate 84 providing methyl benzonorbornadien- yl-l-carboxylate 85 in 30% yield (based on o-nitrobenzenesul- fonic acid from which the benzyne precursor was prepared).41 41 Table 3. Adducts derived from two diaryne equivalents with various dienes. Precursor Diene Bis-adduct Yield Isomer (%) Ratio N \>' <3 C’O‘D 79 77:23 C c 77 53:47 B “ 81 81:19 A / D 3 p 78 57:43 93 91:9 \ A / Ph Mainly A -N 77 single isomer h E ratio 3 E 57 not known 42 The dimerization of cyclopentadienyl-l-carboxylate 84 is very facile at 10-25°C which is necessary for the thermal decomposition. Irie and Tanida considered that a benzyne generated at a lower temperature might give a better result and used for this purpose 1-aminobenzotriazole and LTA. Thus the benzyne generated at -60°C in methylene chloride was successfully added to 84 giving 85 in 85% yield.42 93;: + See» COZCH, 85 (30) N\ >v + 84 ———> 85 (85 ) ’1‘ NH, As the first example using DABT with a carbonyl-contain- ing diene, reaction of 40 with diethyl 3,4-furandicarboxylate 8643 and LTA gave the desired bis-adduct 87 in 40% yield. This substance melted fairly sharply at 188-190°C, suggesting that it was mainly one isomer. The structure. of 87 is based on its spectral properties. The 250 MHz 1H NMR spec- trum had a two-proton aromatic singlet at 5‘7.45 and a four-proton bridgehead singlet at 5 5.90 in addition to a typical triplet and quartet for the ethoxyl group (154.30, 8H, q, .1 = 7 Hz and 1.35, 12 H, t, .1 = 7 Hz). The 13c NMR spectrum of 87 showed the seven major peaks which are required for a single isomer. The compound showed a parent 43 peak at m/e 498 and 425 (IF-ester) in its mass spectrum and had an infrared spectrum showing strong carbonyl absorption at 1695 cm‘l. R R R \ 0,51 pbcom. “02¢ 025* 40 + O :, me’O‘.’ / 0,51 5‘02 0,51 R ' R 86 R=H 87 R=H (40 9i) 33 R=CH, 89 R=CH, (67 %) Reaction of 40 with diethyl 2,5-dimethylfuran-3,4-dicar- boxylate 8844 gave the bis-adduct 89, mp 233-236°C in 67% yield. Compound 89 gave the correct analysis for a bis-ad- duct and its mass spectrum contained a parent peak at m/e 554. The 13C NMR spectrum had eight major peaks indicating that 93 was mainly a single isomer. In contrast to symmetrical dienes, a question of regio- selectivity arises when the dienes are unsymmetrically substituted. The Diels-Alder reaction of 40 with unsymmetri- cal dienes could give rise to two regiochemically distinct products each of which again jprovides two stereoisomers, syn and anti, thus resulting in four isomers altogether. It was found in practice, however, that only the "trans"-type isomer formed with several dienes. For example, treatment of 40 and methyl 2-furoate 9043 at room temperature with LTA gave the diadduct 91 in 47% yield. The structure of 91 was unequivocally determined by its spectral properties and chemical transformations. The adduct melted fairly 44 sharply at 240-242°C suggesting that it was mainly one isomer. The 250 MHz 1H NMR spectrum contained a singlet at 67.35 for the aromatic protons clearly indicating one regioisomer and four other singlets at 5 7.10, 7.08, 5.74, and 4.07 for vinyl, bridghead, and methyl protons. The adduct analyzed correctly for C18H1406 and the infrared spectrum showed the expected carbonyl band at 1760 cm'l. The 13C NMR had mainly nine peaks confirming the presence of a single isomer. 0,6H, ‘ PbCOAc), 40 + 0 :’Only / 90 not In order to prove structure 91 with certainty, it was desired to aromatize compound 91. Among many other possibilities, aromatizations by dehydration45 was adapted. The bis-adduct 91 was reduced catalytically, followed by acid treatment in refluxing ethanol with the hope that it would provide the anthracene derivative 92. However, the corresponding trans-esterified material 93 was obtained along with only a trace of aromatized product 92. Therefore 45 it was thought that more severe conditions might be required for the dehydration. When the aromatization of 93 was carried out in acetic anhydride in the presence of conc. hydrochloric acid, the desired product 94, mp 185°C [lit.46 185°C] was obtained in 81% yield. Compound 94 has a singlet for the two central aromatic protons at 5 9.67, two aromatic multiplets centered at 6 8.31 and 7.50, and typical ethyl signals at 5‘4.53 and 1.51 (J = 7 Hz) confirming the 'trans' arrangement of the ester functions. O¢CH3 H 91 ' Pd/C EtOH HCI EIOH (HazEt 93 Aczo @©© Comcfflfl 46 The Diels-Alder reaction of 40 with dimethyl 4,5-diphen- ylfuran-2,3-dicarboxylate 98 was particularly interest- ing because the diene is not only unsymmetrically substituted but also contains two electron-withdrawing (ester) groups. It should be mentioned that the vast majority of Diels-Alder reactions involve an electron-rich diene and an electron-de- ficient dienophile. The diene 98 used in this reaction was prepared in overall 34% yield by condensation of benzoin 95 with dimethyl acetylenedicarboxylate 96 and potassium carbonate, followed O,CH, OH I K2003 Ph COCH Ph—C—CH-Ph + III 1 = 95 OZCH3 Ph 7°2CH3 96 110‘ O P \ / o,CH, PH O’CHs’ 98 by dehydration of 9747. Treatment of 40 with 98 and LTA in refluxing tetrahydrofuran gave the bis-adduct 99, mp 283-287°C in 78% yield. However, when the reaction was carried out at room temperature, no bis-adduct was observed and only the starting diene was recovered quantitatively. 47 So far, this is the only diene which required vigorous T” \ )4 + 98 -——> \u 'f NH 40 ’ conditions for bis-annulation. The structure of 99 rests ' on its spectral properties and elemental analysis. The 250 MHz 1H NMR spectrum of 99 had a singlet at 58.11 for the two central aromatic protons, a broad twenty-proton aromatic multiplet (5 7.45-7.1) and two singlets at 5 3.97 and 3.61 for the two ester’ methyl groups. The infrared spectrum had two strong ester carbonyl absorptions at 1755 and 1725 cm'l. A valuable result which further demonstrates the useful- ness of the precursor 40 was obtained from the reaction with a halogen-substituted furan. Treatment of 40 with 3-bromofuran 100 furnished the bis-adduct 101, mp 115°C (decomp) in 69% yield. The 250 MHz 1H NMR spectrum of 101 revealed a singlet at 6 7.32 for the aromatic protons suggesting that the product was the 'trans' isomer, as .well as a doublet (i = 2 Hz) at 5 6.96 for the vinyl protons and a broad singlet for the bridgehead protons (a to bro- mine), and doublet (A = 2 Hz) for the other bridgehead protons ( 5 to bromine) at 5 5.69 and 5.38 respectively. Compound 101 gave the correct analysis for the bis-ad- 48 duct, and its mass spectrum had a parent peak at m/g 368 with the typical isotope pattern for two bromines, and a peak at mflg 289 (M+-bromine). 3' P b (OAc)4 Br .. . .\ gg‘g / Br 101 100 Another important group of dienes studied was the fully methyl-substituted dienone 9. 2,3,4,5,6,6-Hexamethyl- cyclohexadiene-l-one 9 formed the bis-adduct 102 with DABT-- LTA in 79% yield. Its structure determination is somewhat complicated and will be discussed in detail in a separate chapter (see page 103). 40 + 4 9 ' 102 1,3-Dipolar cycloaddition is one of the» most useful methods for preparing afive-membered heterocycles. Numerous possibilities for variations are available by changing the structures of both the dipole and dipolarophile. The cycloaddition reaction between benzyne and nitrones (azo- methine oxides) was first reported by Huisgen in 1961.48 For example, benzyne generated from benzenediazonium carbox- ylate adds to N-methyl-a-phenyl nitrone 103 to give a stable adduct 104 in quantitative yield. Similarly, cyclic nitrone 105 gave the adduct 106 with benzyne in excellent yield. H>=N\O_ Ph Ph . 103 ‘ J—CH’ e 104 100% ,2 ( ) o; ' 4 /N’ 105 O 106 (92 %) In principle, any reaction between 40 and a nitrone could give four products, i.e., two regioisomers with two stereoisomers as in the case of unsymmetrical dienes. However, regioselectivity was also observed in the dipolar cycloaddition of 40 with nitrones. The reaction of 1,5-diamino-benzo[1,2-d:4,5-d']bistriazole 40 with N-meth- yl- a-phenyl nitrone 10349 and LTA gave the only 'trans' regioisomer 107, mp 142-143°C, in 91% yield. The structure of 107 follows from its analytical and spectral properties. The 250 MHz 1H NMR spectrum had three singlets at 5 6.42, 5.04 and 2.94 for the central aromatic, benzylic and N-methyl hydrogens in a ratio of 1:1:3, and multiplets at 5 7.38-7.33 for the ten aromatic hydrogens. The mass spectrum showed 50 a parent and base peak at m/e 344 and major fragmentation peaks at m/_e_ 329 (IF-methyl) and 267 (M+-phenyl). The 13C NMR spectrum showed mainly nine peaks indicating the presence of a single isomer. 4° " ="\D ———> H.c—-N 103 107 (91 %) Similarly, the reaction of 40 with the bulky nitrone 108 at room temperature afforded the bis-adduct 109, mp 239-241°c in 78% yield. The 250 MHz 1H NMR spectrum consist- ed of six singlets showing mesityl, central aromatic and benzylic hydrogens at 5 6.85,‘ 6.14 and 5.66 in a ratio of 4:2:2 and three methyl signals at 52.96, 2.30 and 2.27 in a ratio of 6:12:6. The 13C NMR spectrum showed mainly. eleven peaks for a single isomer. The mass spectrum had a parent and base peak at m/g 428 and major fragmentation peaks at m/g 384 (84) and 309 (M+-mesityl). 40 + =N\o ————> Hp—N —-0H, 108 109 (78%) 51 The remarkable degree of regio and stereospecificity in these cycloadditions strongly suggests that they occur stepwise. The results are summarized in Table 4. It was hoped that an unsymmetrical bis-adduct could be prepared by using two different dienes in succession as trapping agents. A mixture of DABT and 1 equiv. of 2,5-dimethylfuran in THF was treated with 1 equiv. of LTA. \ 1.1 Gauiv / N\>N 2.1eqlgiv LTAy' a” ‘.m '3‘ 31mm 03 NH, 4 1equ1v LTA /\z-—z .2“ 40 110 Upon completion of the addition of LTA, furan was added to the reaction mixture followed by more LTA. The products, isolated after the usual workup, turned out to be 1,4,- 5,8-tetramethyl-1,4,5,8-tetrahydroanthracene-1,4:5,8-diendox- ide 73 and 1,4,5,8-tetrahydroanthracene-1,4,5,8-diendoxide 71 and no unsymmetrical adduct 110. Probably the intermed- iate 111 resulting from the addition of one equivalent of aryne to the diene 72 is more soluble than DABT in the solvent and reacts further to give the symmetrical adduct 73. In fact treatment of DABT and 1 equiv. of 2,5-dimethylfuran with LTA gave the bis-adduct 73 and the unsymmetrical adduct 111 was not observed. 52 Table 4. Adducts of DABT-LTA with various dienes with functionality. Diene Adduct mp , °c Yield (7.) mazEt \ (3 / 0,151 a = c0,CH,CH, o \ O,Et E lg, 233-236 67 0,51 s E=COZCHzCH3 188-190 40 o,c H, 240-242 47 115 (dec) 69 53 Table 4 (continued) ‘0 o 338 (dec) Ph Ph ..~ 283-287 7.1’ E E E==CO,lCH3 142-143 239-241 79 78 91 78 54 1"” \ 1 equilflL TA )q 40 1' 1 EQUIV. II ;’ N e / \ 111 P 73 It was thought that mono-amino compound 64 might behave as a diaryne equivalent in a stepwise process, and that it might be a useful precursor of unsymmetrical adducts. However, 1-aminobenzo[1,2-d:4,5-d']bistriazole 64 didn't seem to react with LTA in THF probably due to its insolubility; the unreacted amino compound 64 was recover- ed unchanged. H I /"' N\\ , \ LTA N\ N + 1equ1v.O ———>NO \N N/ / REACTION I NH, 64 It was quite interesting to study the oxidation of 1,6-diamino-benzol1,2-d:4,5-d']bistriazole 63 which contains 1-amino- and 2-amino-moieties in the same molecule. Unlike 1-aminobenzotriazole, 2-aminobenzotriazole 48 does not behave as a benzyne precursor.18 Iodobenzene diacetate is known 55 to oxidize 2-aminobenzotriazole 48 to cis,cis muconitrile 114 in 98% yield, presumably through the nitrenes 112 and 113.18 Compound 114: has also 'been obtained. in 64% jyield by the oxidation of o-phenylenediamine 115 with LTA, in which the nitrene 113 is a possible intermediate.50 Thus, oxidation of 48 with LTA in the presence of 1,2,3,4-tetra- phenylcyclopentadienone 14 gave no adduct and the diene [O] .. 0.. C / —NH2 ——_> C / 4:'—9 / \ \ / \ N N . 113 14 was recovered.18 48 112' T LTA NH, NH, 115 ,. o PblOAc), 43 + Ph Ph 9 N0 ADDUCT Ph ,4 Ph Oxidation of compound 63 with lead tetraacetate brought about a rapid evolution of. nitrogen, and when 2,3,4,5,- 56 6 , 6-hexamethyl-2 , 4-cyclohexadienone 9 was present as the trapping agent, 1,3,3,4,7,8-hexamethyl-5,6-bis(Z,Z-cyano- methylene)-bicyclo[2.2.2]oct-7-ene-2-one 116 was obtained in 81% yield. The infrared spectrum showed both nitrile NHZ ' I e O I 2 saw. u N I i \\ \ /HH’* 5 c 63 9 and carbonyl bands at 2215 and 1740 cm“1 respectively. The 250 MHz 1H NMR (09013) spectrum of 116 had bands at 5 1.77 and 1.70 for two homoallylically coupled methyl groups (1 = 1.0 Hz), four separate aliphatic methyl singlets at 5 1.46, 1.41, 1.09 and 0.89 and two vinyl singlets at 55.66 and 5.62. The 13C NMR spectrum showed a carbonyl carbon at 199.50, eight vinyl and nitrile carbons at 5 161.28, 155.75, 139.52, 129.98, 116.54, 115.87, 98.06 and 96.13, three quaternary carbon signals at 560.06, 52.24 and 45.71 and six methyl carbon peaks at 5 23.58 (overlap), 14.25, 13.90, 11.99 and 11.62. High resolution mass spectral analysis established the elemental composition. The mass spectrum showed a parent peak at 313/3 280, and a base peak at mfg 210 indicating a loss of dimethylketene (IN-70). In view of previous oxidation studies of 1- and 2-aminobenzotriazoles, two pathways can be suggested to account for the formation of compound 116 (Scheme 5). H u”... .. _, m a N 4 N N \ / l \ B N\ /N O N N M N /N N N .h. ,. \ m / \ / \ h P ,1 ill. IV IIV ill. 0 / \ / \ / \ 2 "(N \N N .N 1. / C N\ N m m , u , IIV 1 Mn N /N\ .W N / \ N ”w .N“ w W do w w / a , w m m , b 5 A "2 e h 2 l "NlN N m t N N N o. m P8 MIN N H"... / \\ /N\\ O c / \\ NilN \N N S N /N\ 58 It was thought that the oxidation of 63 in the absence of any trapping agent might lead to the compounds 117 and/or 118. However, the only product obtained was a polymeric oil. /CN 11 H \u 117 Nah—7 raw-— 118 It was thought that 155-diamino-benzo[1,2-d;4,5-d']bis- triazole 40, might dimerize on oxidation with only one equiva- lent of lead tetraacetate. In the oxidation of 1-aminobenzo- triazole with LTA in methylene chloride, the benzyne generated Pk§~ LTAI ” ’/.j /‘ CH,CI \ T th ‘HZ(?370 dimerized to give biphenylene 1218 in high yield. When DABT was oxidized with one equivalent of LTA, no desired biphenylene 119 or oligomer thereof was detected. It is tempting to assume that the failure of dimerization is due to further oxidation (as can be understood from the example given below) of the product 119 leading to more complicated products. 59 NH, NH, I N/N "\X 1""2‘“ N/" / I—l \ \N \\ / LTA \\ \ —-1 / 7’ ""2 119 NH: 40 1-Aminobenzotriazole is known to undergo a cross-coupling reaction with other analogous aryne precursors by cooxidation with LTA.51 Barton and Jones reported an unsymmetrical biphenylene 121xobtained from cooxidation of 1-amino-lH-naph- tho[1,2-d]triazole 120 and l-aminobenzotriazole 6.51a N971 a “ H": (j), 3:, O 120 6 NH, 121(367.) Among the cycloaddition reactions that have some general- ity and synthetic utility are the [2+2] cycloadditions of benzyne with alkenes. Benzyne generated from benzenediazonium 2-carboxylate adds to vinyl acetate in good yield.52 However, oxidative generation of benzyne in vinyl acetate gave bipheny- lene in high yield and only a trace of 1,2-adduct, benzocyclo- butenyl acetate 12218. Reaction of DABT with vinyl acetate and LTA gave no cycloadduct. An electron-rich dienophile, 1,1-dimethoxyethy1ene,53 also showed no reactivity t0ward the DABT-LTA. 60 N \>, + = LTA / r---—- N \OECH’ ——’ \ l—— NH 0 ' \OIICH’ 6 2 122 (Trace) o In conclusion, we have synthesized 1,5- and 1,7-di- amino-benzo[1,2-d;4,5-d']bistriazole (DABT) and demonstrated their utility as diaryne precursors. The most interesting aspect of the Diels-Alder reaction with unsymmetrical dienes and 1,3-dipoles is that each reaction is regiospecific in that, of the two possible orientations, only the 'trans' product is produced. The remarkable degree of regio- and stereospecificity encourage one to further study the reasons for this specificity as well as to seek out further synthetic applications of DABT. C. Preparation of Polyphenylarenes Using DABT The bis-annulation technique has been usefully extend- ed to the synthesis of various polyphenyl arenes, which are easily prepared in high yield by reaction of DABT and LTA with an appropriate diene. Among many dienes, tetraphenylcyclopentadienone 14 has always been a good candidate for testing aryne cycliza- tion as shown in Table 5. For example, 1,2,3,4-tetraphenyl- naphthalene 15 was readily synthesized by using this method. 61 Table 5. Adducts of 1,2,3,4-tetraphenylcyclopentadienone with various benzyne precursors. Precursor Product Yield Reference (1») Ph ' "a " N)“ 95 18 | , l1 ' "Hz N; 0 same 95 55 02’ 1’-Ph . same 82-90 56 0; Ph Ph \\ 30C 73 1, .(fl Ph NH, Ph 50 51b 62 Ph - Ph N\\ Pb (OM94 + o a I Ph "”2 Ph 6 14 O .. Ph 15 However, the addition of benzyne to the related dienone, 7,9-diphenyl-8-H-cyclopenta[a]acenaphthylene-8-one(acyclone, 123) in boiling xylene gave the fluorescent adduct, 7,12-di- phenylbenzo[k]fluoranthene 124 in only 8% yield, with a 50% yield of biphenylene. The low yield was due to insolubility of the dienone.18 Ph Ph 0 1, . 6 +0 6. xylene A Ph Ph 123 124 Treatment of DABT with two equivalents of 14 and LTA in boiling THF gave 1,2,3,4,5,6,7,8-octaphenylanthracene, 63 125, mp 415-417°C in 56% yield. However, when the reaction lilH, Ph Ph N N\ Pb(0Ac), P" / \ a -+ 14 r \ )A - 2 c0, T P 40 NHz‘ Ph Ph 125 was carried out at room temperature, compound 125 was obtained in only low yield (7%) in addition to much unreacted dienone. Perhaps, the low yield was due to the poor solubility of the presumed intermediate 126 at room temperature. Ph NH, 1. ,, N/ \\ N Ph 126 P“ The 250 MHz 1H NMR spectrum (d6-DMSO, 110°C) of 125 had a sharp singlet for the .central aromatic hydrogens at 57.33 and aromatic multiplets at 5 7.1-6.7. The mass spectrum of 125 showed a strong M+ peak (m/g, 786, intensity 71). Treatment of 40 with LTA and 2,5-methoxycarbonyl- 3,4-diphenylcyclopentadienone 12754 gave a yellowish green bis-adduct 128, mp 375-376°C in excellent yield (93%). The structure of 128 was based upon its chemical and spectral properties. The 250 MHz 1H NMR spectrum, with a singlet Ph Ph 64 at 5 8.55 for the two central aromatic protons, twenty-proton_ aromatic multiplets at 57.25-7.07 and a singlet at 6 3.65 for four ester methyl groups, was consistent with the structure. The 13C NMR spectrum of 128'had only ten peaks as required by symmetry with appropriate chemical shifts. The IR spectrum of 128 had a strong ester carbonyl band at 1721 cm‘l. The mass spectrum had a parent and base peak at m/g 714 and a weak fragmentation peak at _m/_e_ 683 (M+-methoxyl). O,CH, Ph Pb (0A0). 40 '1' O -2CO 02¢”: 127 128 Reaction of DABT with LTA and, N-methyl-2,3,4,5- tetraphenylpyrrole 12939 afforded the bis-adduct 130, mp 205-207°C in 88% yield. Compound 130 gave the correct analysis for a bis-adduct and its 250 MHz 1H NMR spectrum consisted of a multiplet at 57.8-6.6 for aromatic protons and a broad singlet at 5 2.12 for the methyl groups. Hart and Lai attempted to prepare a similar bis-adduct 131 from the reaction of tetrabromo-p-xylene 76 with the same diene 129 and n-BuLi. However, the bis-adduct was not formed.39 65 Ph \ “ LTA 4° " “"N / h THF ' h 129 130 B Br 0 + 129 B Br 76 131 Treatment of DABT with 2,5-diphenylfuran 132 and LTA gave a bis-adduct, 133, mp 264-265°C in 75% yield. Compound 133 gave a correct analysis. The 250 MHz 1H NMR spectrum showed an aromatic multiplet at 5 7.67-7.25 and a vinyl singlet at 5 6.74. The mass spectrum of 133 had a parent and base peak at m/g 514 and a major fragmentation peak at m/g 498 (IF-oxygen, intensity 18). Ph Ph Ph \ Pb‘OAC)‘ ‘ 40 + > . _ / 9,, Ph Ph 132 133 66 Campbell and Rees reported that the formation of benzyne adduct 135 was complicated by competing oxidation of the diene to o-dibenzoylbenzene, but with a large excess of the diene adduct 135 was obtained in reasonable yield (43%).18 The oxygen bridge of 135 was easily removed to give 9,10-diphenylanthracene 136 in 88% yield.57 Ph "\\ /" + o T / P11 NH 5 z ‘34 h135 (43%) Zn,l-l* Ph Ph 136 (88%) Similar bis-adducts were prepared in good yields in this laboratory using tetrabromobenzene derivatives (76 and 138) as diaryne equivalents.58 R f B B n'BuLi ‘1' 134 Toluene 8 Br - 78° c R 76 R =CH: 137 R=CH, (67%) . 138 R =OCH3 139 R=OCH3 (42%) 67 The reaction of DABT with diene 134 gave a diadduct 140 in much higher yield (88%) than obtained in the analogous reaction with 6. The difference in yields may be explained by the difference in reaction procedure. For the synthesis of 135 a solution of 1-aminobenzotriazole in dry benzene was added to a stirred suspension of LTA and the diene 134 at 25°C in the same solvent. In this case, LTA also oxidize the receptor diene to o-dibenzoylbenzene. On the other hand, for the. bis-annulation of DABT, an' inverse addition was always applied as described in previous chapter (i_._§;, addition of LTA to a mixture of DABT and diene). Since oxidation of DABT by LEA is very fast, the competing reaction between DABT and the diene 134 may not be possible. Compound 140 analyzed correctly. Although the 250 MHz 1H NMR spectrum showed complicated multiplets in the aromatic region ( 8.2-6.85), the 13C spectrum had mainly ten signals confirming that only one isomer was formed. All of these results are summarized in Table 6. TH: Ph Ph l" N§‘ 4- 134 .liing, K N) THF ' I NH; . . 140 The removal of the oxygen bridges of 140 was performed by treatment with Zn-TiC14 in boiling THF for 20 h to yield 81% of 5 , 7 , 12 , 14-tetraphenylpentacene 141 . 59 Pentacene 141 is very reactive, and in solution absorbs atmospheric 68 Table 6. Di-adducts of DABT-LTA with various dienes. Diene Di-adduct Yigld mp(°C) 56 415-417 93 375-376 88 205-207 75 264-265 88 306-308 69 oxygen (very rapidly in sunlight) to give the peroxide Zn TiCl 140 l ‘ THF A 20r1 141 by 142 as reported in the literature.59‘6O The deoxygenation of 137 and 139 was studied by Hart and Shamouilian.58 When compound 137 was refluxed in acetic acid with Zn dust Zn dust 143 CH,CO,H rollux Ph Ph 137 144 70 for 2 h, reaction did not proceed to give pentacene 143; rather it gave the quinonedimethide 144 in quantitative yield. However, similar treatment of 139 with Zn in acetic acid provided the expected pentacene 145. Zn dust CH,CO,H reflux 139 . It was interesting to study the Diels-Alder reactivity of the 5,7,12,14-tetraphenylpentacene 141. Biermann and Schmidt studied Diels-Alder reactivity of many polycyclic aromatic hydrocarbons with maleic anhydride.61 The struc- tures of the primary Diels-Alder adduct were deduced from the UV spectra of the reaction mixtures taken at regular intervals. Pentacenes were predicted to give adducts at the central aromatic ring as shown below: 71 Interestingly, Russian workers reported that pentacene reacted with benzoquinone to yield two adducts, of symmetrical (148) and unsymmetrical (149) structure.62 149 (15.4%) Compound 151, mp 375-376°C, previously unknown, was prepared in high yield (85%) by treatment of pentacene 141 with one equivalent of dimethyl acetylenedicarboxylate. The structure follows from its analysis and spectral prOper- ties. The infrared spectrum of 151 had a strong carbonyl band at 1715 cm'l. The.250 MHz 1H NMR spectrum had a multi- plet at 6 7.40-7.20 for the twenty phenyl protons and an AA'BB'; system‘centered at 5 7.50 and 7.13 (i = 4 Hz) for eight aromatic protons. In addition, there were two sharp singlets at 6 5.58 and 3.74 for two bridgehead protons and six ester protons, respectively. The 13C NMR spectrum showed only thirteen signals as required by symmetry. The 72 cn,o,c-csc-co,c H, 96 141 152 153 mass spectrum had a parent and base peak at r_n_/_e_ 724. Compound 153 was obtained in fair yield (46%) from the reaction of 141 and maleic anhydride 152. The 250 MHz NMR spectrum was clear-cut, with a peak for two bridgehead 1 Hz) coupled to the two hydrogens protons at 5 5.06 (g ato the carbonyl groups at 63.52 (i = 1 Hz), in addition to multiplets at 57.45-6.95 for the aromatic hydrogens. The.compound was found to be very unstable and even on mild heating underwent a retro Diels-Alder reaction. Therefore, compound 153 was isolated by washing the crude product with ethyl ether to remove impurities. Measurement 73 of the melting point was attempted in a sealed capillary tube. Above 75°C, it showed a blue color and became a blue solution on further heating, presumably due to reformation of 141. Its~ mass spectrum had a strong peak at g/g 582 (Iv-maleic anhydride, intensity 50) indicating a retro Diels-Alder reaction. In summary, it was demonstrated the diaryne equivalent 40 can be converted to polyphenyl anthracenes or pentacene in one (or two) steps. This methodology can be applied as a powerful tool to synthesize various other polyphenylated arenes . 74 Experimental 1. General Procedures. 1H NMR spectra were measured at 60 MHz (Varian T-60) or at 250 MHz on a Bruker VIM-250 spectrometer using (CH3)4Si as an internal standard. All chemical shifts are recorded in 5 units. 13C NMR spectra were measured at 62.89 MHz on a Bruker WM-250 spectrometer, IR spectra were determined on a Perkin Elmer Model 167 spectrometer. UV spectra were obtained on a Cary 219 spectrometer. Mass spectra were measured at 70 eV using a Finnigan 4000 spectrometer with the INCOS system, operated by Mr. Ernest Oliver or Mr. Richard Olson. Melting points were determined with an electro-thermal melting point appara- tus (Fisher Scientific) or a Thomas Hoover Unimelt apparatus. Microanalyses were performed by Spang Microanalytical Labora- tory, Eagle Harbor, Michigan or by Guelph Chemical Labora- tories Ltd., Guelph, Ontario, Canada. 2 . Diethyl 2 , 5-diam1no-1 , 4-benzenedicarboxylate (44) . A mixture of 20 g (78.7 mmol) of diethyl 2,5-diamino-1,4-di- hydroterephthalate 4328 and 1 g of 10% palladium on carbon in 200 mL of cumene was refluxed for 12 h. The catalyst was removed by filtration and the filtrate was concentrated under reduced pressure to provide 17.6 g (89%) of crude product which was recrystallized from ethanol, mp 168°C, orange needles [lit.28 168°C]; 1H NMR (CDC13) 5 7.2 (s, 2H), 4.3 (q, 1 = 7.1Hz, 4H), 5.4 (broad s, 4H), 1.35 (t, ,1 = 7.1Hz, 6H); mass spectrum, mfg (relative intensity) 75 252 (100), 224 (20), 207 (26), 196 (15), 178 (63), 150 (23), 132 (53), 105 (13). 3. 1,5-Bis[acetylamino]-2,4-dinitrobenzene (51). A mix- ture of 1,5-diamino-2,4-dinitrobenzene30 (99 g, 0.5 mol), acetic anhydride (100 mL) and cone. sulfuric acid (20 mL) was heated under reflux for 6 h. The clear brown solution was then allowed to cool to room temperature and poured into water (3000 mL) with stirring. After the excess acetic anhydride had hydrolyzed, the brown solid was collected by filtration, washed with water and dried to yield 128 g (90%) of crude product (51). Recrystallization from acetic acid gave pure product: mp 226°C (lit.29 mp 228°C); 1H NMR (CDC13) 510.64 (broad s, NH—), 10.32 (s, 1H), 9.22 (s, 1H), 2.1 (s, 6H); mass spectrum, mlg (relative intensi- ty), 282 (3), 236 (95), 194 (100), 168 (22), 148 (11). 4. 1,7-Diacetylbenzo[1,2-d:4,5-d']bistriazole (53). 1,5-Bis- [acetylaminOJ-Z,4-dinitrobenzene (12 g, 0.0425 mol) suspended in absolute ethanol (150 mL) was hydrogenated over 3 g of 10% Pd on C on a Parr apparatus (60 psi). After removal of the solvent by filtration, the filtrate was dissolved in 400 mL of water and the catalyst* was removed by filtration. The filtrate was treated with cone. hydrochloric acid (20 mL) and a solution of sodium nitrite (8.89 g, 0.1275 mol) in water (40 mL) at 0°C over 30 min. I"The catalyst was recycled after washing with 20% aqueous potassium hydroxide solution and water. 76 The product was collected by filtration, washed with water and dried to yield 9.6 g (93%) of pure 53: mp 205°C (recrystallized from ethyl acetate/hexane as yellow needles) (111:.29 mp 239°C); 1H NMR (250 MHz, 013013) 69.14 (d, ,1 = 1 Hz, 1 H), 8.87 (d, g = 1 Hz, 1H), 3.06 (s, 6H); mass spectrum, m/g (relative intensity), 244 (16), 202 (38), 174 (8), 160 (56), 43 (100). 5. Amination of benzo[1,2-d:4,5-d']bistriazole 39 with hydroxylamine-O-sulfonic acid (54). Benzo[1,2-d:4,5-d']bis- triazole?!9 (6 g, 0.0375 mol) was dissolved in a solution of potassium hydroxide (19.8 g, 85% purity, 0.352 mol) in water (200 mL) at 60°C. Solid hydroxylamine-O-sulfonic acid (16.95 g, 0.15 mol) was added in portions during 1 h, the temperature being maintained at 66-68°C. The mixture was then stirred for 1 h at ca. 65°C, cooled and filtered. The alkaline solution was continuously extracted with ether for 72 h. Removal of the ether gave 3.2 g (45% yield) of a separable mixture of three isomers, 1,5-, 1,7-, .and 1,6-diaminobenzo[1,2-d:4,5-d']bistriazoles in a ratio of 53:12:35. Recrystallization ,from ethanol afforded 1.4 g of pure 1,5-isomer (40) as an off-white solid. A few more) crystals (0.58» g) (a. mixture of 1,5- and 1,7-iso- mers) were obtained from the mother liquor. Concentration of the mother liquor gave mainly the 1,6-isomer (63) (1.2 g, purity )95%, determined by integrating the peak at 5 8.24 and 6 8.59, 7.96 of 1H NMR spectrum). After extraction the resulting basic solution was neutralized with 10% aqueous 77 hydrochloric acid to provide a mixture of mono-aminated products (3.2 g, 48% yield). For 1,5-Diamino-benzo[1,2-d:4,- 5-d']bistriazole (DABT) (40): mp 292°C (decomp); 1H NMR (250 MHz, d6-DMSO) 58.24 (s, aromatic H), 7.18 (s, -NH2); 130 NMR (d6-DMSO) 5 144.16, 131.40, 97.43 coupled 13c NMR (d6-DMSO) 5 144.38 (3.1 = 1 Hz), 131.65 (A = 1 Hz), 99.13, 96.37; mass spectrum, g/g (relative intensity) 190 (16), 162 (14), 133 (27), 118 (19), 105 (100), 78 (52), 63 (45), 51 (66); IR (KBr) 3386, 3610, 3020, 1600, 1520, 1440, 1310, 1040, 923 cm-1. Anal Calcd. for C6H8N3: c, 37.90; H, 3.18; N, 58.92. Found: C, 37.96; H, 3.18; N, 58.81. For 1,7-diamino-benzo[1,2-d:4,5-d']bistriazole (41): mp 263°C; 1H NMR (250 MHz, 'd6-Duso) 5 8.69 (d, 1H, 4 = 1Hz), 7.71 (d, 1H, g_= le), 7.09 (s, 4H, -NH2); 130 NMR (d6-DMSO) 5142.93,133.32, 108.42, 87.43; coupled 13c NMR (d6-DMSO) 5142.92 (,1 =1 Hz), 133.26 (,1 = 1 Hz), 109.78, 107.07, 88.83, 86.045 mass spectrum, ,m/g, (relative intensity) 190 (13), 162 (12), 147 (7), 133 (39), 105 (100), 78 (61), 63 (29), 51 (57); IR (KBr) 3320, 3275, 3160, 1635, 1375, 1310, 1278, 1262, 1180, 1090 cm‘l. High resolution mass spectrum: Calcd. for C6H6N3: 190.07154; Found: 190.07157. For 1,6-Diamino-benzo[1,2-d:4,5-d']bistriazole (63): mp 271-273°C as a light-tan solid from ethanol: 1H NMR (250 MHz, d5-DMSO) 58.59 (d, 1H, _J_ = 1H2), 7.96 (d, 1H, d = le), 7.09 (s, 4H); 130 NMR(d6-DMSO) 5143.36, 139.98, 138.87, 132.72, 104.63, 91.08, mass spectrum, n/e (relative intensity) 190 (2), 184 (6), 175 (17), 160 (74), 147 (30), 78 132 (35), 118 (26), 105 (20), 9O (39), 85 (33), 77 (58), 52 (100); IR (KBr) 3280, 3170, 1600, 1260, 970, 840 0111-1. High resolution mass spectrum: Calcd. for C6H6N8: 190.07154; Found: 190.07194. For 1-Amino-benzo[1,2-d:4,5-d']bistriazole (64): mp ) 400°C as a light-tan, solid from ethanol: 1H NMR (250 MHz, d6-DMSO) 5 8.10 (d, 1H, ,1 =1Hz), 7.65 (d, 1H, ; = 1H2), 6.83 (s, 2H); 130 NMR (d6-DMSO) 5 146.19, 144.96, 142.18, 130.54, 101.60, 90.66; mass spectrum (not available because of the high melting point of the product); IR (KBr) 3250, 1620, 1313, 1282, 1180, 1120, 875, 847, 805 cm‘l. 6. O-(2,4-Dinitrophenyl)hydroxylamine (57). The following procedure is an improvement on the method of Tamura.32° The reaction using the same procedure and scale as described by Tamura, gt. $1., always gave starting material. Conse- quently, a modified procedure was developed which is quite different in terms of material balance and reaction time. To a stirred solution of ethyl O-(2,4-dinitr0phenyl)aceto- hydroxamate32° (3 g, 11.15 mmol) in dioxane (30 mL) was added 70% of perchloric acid (20 mL, 223 mol) at 25°C over 10 min. Stirring was continued at room temperature for 20 h and the mixture was then poured into ice water to give a yellow solid which was filtered and washed with water. Recrystallization from ethanol afforded 1.45 g (65%) of 57 as pale yellow needles; mp 112-113°C (lit.32c mp 112-113°C); 1H NMR (00013) 58.7 (d, ,1 = 3 Hz, 1H), 8.4 (dd, 4 = 10 and 3 Hz), 7.9 (d, ,1 = 10 Hz, 1H), 6.9 79 (broad s, 2H, -NH2). 7. Amination of benzo[1,2-d:4,5-d']bistriazole with 0-(2,- 4-dinitrophenyl)hydroxylamine. To a solution of 6 g (37.5 mmol) of benzobistriazole 39 in 160 mL of dry dimethyl- formamide under Ar was added 3.3 g (2.2 equiv.) of 60% sodium hydride oil dispersion (NaH was freed of mineral oil by washing with dry hexane) for a period of 5 min. The mixture was then stirred at 90-100°C for 1 h. After cooling, to room temperature, 14.93 g (75 mmol) of O-(2,4-di- nitrophenyl)-hydroxylamine in 120 mL of dry DMF was added over 30 min. The mixture was stirred at room temperature for 1 h, then poured into 700 mL of dry ether. The precipi- tated yellow solid was filtered and the filtrate was concen- trated under reduced pressure to afford 8.3 g of a red oil consisting of aminated products contaminated with DMF. An aqueous potassium hydroxide solution 7(12.6 g in 100 mL H20) was added to the oil and the mixture was stirred at 70°C for 1 h. After cooling the product was obtained by continuous extraction with ether for 72 h. The ether extract was evaporated to afford a mixture of three isomeric bis-adducts in a ratio 54:9:37 of compounds 40:41:63. Several runs on this scale gave yields varying from 1.86 g to 4.6 g (26-65%). After extraction, the resulting basic solution was neutralized with 10% aqueous hydrochloric acid to give mono-aminated products which were recycled. 80 8. 1,4,5,8-Tetranethyl-1,4,5,8-tetrahydroanthracene-1,4:5,- 8-diendoxide (73). This is a representative oxidation procedure for the use of DABT 40 as a diaryne equivalent. To a mixture of 0.13 g (0.684 mmol) of DABT and 0.657 g (6.842 mmol) of 2,5-dimethy1furan in 100 mL of dry THF at room temperature was added in portions 0.667 g (1.5 mmol) of lead tetraacetate (LTA) in 30 mL of dry tetrahydro- furan (THF) over a period of 30 min. After 10 min additional stirring, the lead diacetate was filtered, the filtrate was'diluted with 500 mL of water and extracted three times with 100-mL portions of methylene chloride. The combined extracts were washed with saturated NaHCO3 solution, saturat- ed NaCl solution and dried over MgSO4. Removal of the solvent and chromatography of the remaining solid on activat- ed alumina with 1:1 chloroform:hexane gave 0.147 g (81%) of 73 as a mixture of two isomers in the ratio of 19:81 (determined by integrating the peaks at 5 6.78 and 6.76 in the 250 MHz 1H NMR spectrum); white solid, mp 229°C (decomposition).‘ The isomer mixture had the following spectral properties: 1H NMR (250 MHz, CDCl3) 5 6.96 (s, aromatic), 6.78 (s, minor, vinyl), 6.76 (s, major, vinyl), 1.87 (8, major, methyl), 1.86 (s, minor, methyl); 13C NMR (CD013) 5 151.14, 147.26 (major), 147.43 (minor), 110.62 (major), 110.32 (minor), 88.74, 15.33; mass spectrum, m/_e_ (relative intensity) 266 (5), 240 (9), 214 (7), 197 (33), 181 (18), 165 (13), 43 (100); IR (KBr) 3065, 2980, 2935, 1440, 1385, 1305, 1290, 1240, 1135 cm'l. 81 9. 1,4,5,8-Tetrahydroanthracene-1,4:5,8-diendoxide (71). In a procedure similar to that used for 73, reaction of 40 (0.2 g, 1.052 mmol) with excess furan (0.716 g, 10.52 mmol) in dry THF (50 mL) and LTA (1.03 g, 2.32 mmol) gave a crude reaction mixture. Flash chromatography of this crude product over slica gel, eluting with chloroform, gave 0.147 g (80%) of 71 as a mixture of two isomers. Separation of the (isomers was not attempted. The 250 MHz proton NMR spectrum clearly indicated the presence of two isomers in the ratio of 77:23 (determined by integrating the peaks at 5 7.20 and 7.19); white solid, mp 196—203°C (lit.21d syn, mp 191-193°C, anti, mp 245°C). The isomer mixture had the following spectral properties: 1H NMR (250 MHz, CDC13) 57.20 (3, major, aromatic H), 7.19 (s, minor, aromatic H), 7.02 (s,'4H), 5.63 (s, 4H); 13C NMR (CDC13) 5 147.82, 143.56 (minor), 143.40- (major), 114.10 (major), 113.85 (minor), 82.36; mass spectrum, m/g (relative intensity) 210 (41),153 (100), 184 (28), 128 (22); IR (KBr) 3095, 3030, 1440, 1335, 1293, 1155, 995, 860, 750 cm'l. In this experiment when 2.1 mmol .of furan was used under otherwise similar conditions, the yield of bis-adduct decreased to 79%. The reaction was also repeated as follows: To a stirred suspension of 2.57 g (5.79 mmol) of LTA and 1.8 g (26.47 mmol) of furan in 100 mL of dry THF at room temperature under argon, was added 0.5 g (2.631 mmol) of 40 suspended in the same solvent (50 mL) over 30 min (upon addition 82 no evolution of N2 was observed). After additional stirring for 1 h, 5 mL of ethylene glycol was added prior to addition of water (500 mL). Filtration and drying gave 0.5 g of unreacted 40 (quantitative recovery). 10. 1,4,5,8-Tetramethyl-1,4,5,8-tetrahydroanthracene-1,4:5,- 8-diendoxide (73) from 41. In a procedure similar to that used for the preparation of 73from 40, reaction of 1,7-di- amino-benzo[1,2-d:4,5-d']bistriazole 41 (0.31 g, 1.63 mmol) with 2,5-dimethylfuran (0.35 g, 3.64 mmol) in dry THF (100 mL) with LTA (1.59 g, 3.58 mmol) gave a crude product. Chromatography of this crude product over silica gel using 1:1 chloroform:ether as eluent provided 0.35 g (80%) of bis-adduct 73 as a mixture of the syn and anti isomers, ratio 19/81 (determined by integrating the peaks. at 6 6.78 and 6.76 in the 1H NMR spectrum), identical with the inde- pendently synthesized material from 1,5-diamino-benzo[1,2-d:- 4,5-d']bistriazole 40; mp 229°C (decomposition), white solid; 1H NMR (250 MHz, CDC13)56.96 (s, 2H), 6.78 (s, minor), 6.76 (s, major), 1.87 (s, major), 1.86 (s, minor, methyl). 11. 1,4,5,8-Tetramethylanthracene (75). A solution of 73 (0.7 g, 2.63 mmol) in 70 mL of absolute ethanol containing 0.03 g of 10% palladium on charcoal was hydrogenated at 60 psi and room temperature over 2 h. The mixture was filtered and 10 mL of concentrated hydrochloric acid was added to the colorless filtrate. The mixture was refluxed for 1 h, cooled, poured into 200 mL of water and extracted 83 twice with 50 mL of methylene chloride. The combined organic extracts were washed twice with 50 mL of saturated sodium bicarbonate solution and dried over magnesium sulfate. Removal of the solvent under reduced pressure gave crude product which was recrystallized from ethyl acetate to afford pure 75 (0.5 g 83%): mp 220°C [lit.38 221—222°C]; 1H NMR (CDC13)58.53 (s, 2H), 7.15 (s, 4H), 2.73 (s, 12H); mass spectrum, .m[g (relative intensity) 234 (100), 219 (35), 202 (13), 178' (3), 117 (1), '40 (18). 12. Bis-(N-methy1)-2,3,6,7-tetramethyl-1,4,5,8-tetraphenyl- 1,4,5,8-tetrahydroanthracene-1,4:5,8-bisimine (80). In a procedure similar to that used for 73, reaction of 40 (0.267 g, 1.4 mmol) with 2,5-dipheny1-1,3,4-trimethylpyrrole39 (0.73 g, 2.8 mmol) in dry THF (60 mL) and LTA (1.37 g, 3.08 mmol) gave, after workup, a grey residue. Chromato- graphy of this crude product over' silica gel using 2:3 chloroformzbenzene as eluent gave 0.64 g (77%) of a pure isomer (80) which was recrystallized from ethyl acetate/hex- ane; white crystals, mp 273-275°C; 1H NMR (250 MHz, CDCl3) 67.6-7.2(m, 22H), 1.8 (s, 12H), 1.6 (s, 6H); 130 NMR (CDCl3) 5130.52, 130.06, 130.02, 129.04, 128.35, 128.02, 127.72, 31.47, 29.66, 12.70; mass spectrum, ng (relative intensity) 596 (2), 542 (1), 424 (2), 113 (100), 56 (33).; IR (KBr) 3065, 3035, 2940,2860, 1600, 1495, 1450, 1295,1155 cm’l. £441.- Calcd. for C44H40N2: C, 88.55; H, 6.76; N, 4.69. Found: C, 88.23; H, 6.63; N, 4.58. 84 13. Reaction of 40 with 2,3-bis(methylene)-bicyclo[2.2.1]- heptane (83)40. In a procedure similar to that used for 73, reaction of 40 (0.28 g, 1.47 mmol) with 2,3-bis(methylene)-bicyclo[2.2.l]heptane40 (0.39 g, 3.25 mmol) suspended in 100 mL of dry THF with lead tetraacetate (1.5 g,3.38mmo1) gave a grey residue. Recrystallization of the crude product from ethyl acetate/hexane furnished 0.43 g (93%) of 83 as a mixture of the syn and anti isomers, mp 245-250°C, white solid: 1H NMR (250 MHz, CDC13) 5 7.56 (s) and 7.43 (8), (minor), 6.96 (s, major), 3.35 (s, 8H), 2.70 (m, 4H), 1.80-0.9 (m, 12H); mass spectrum, m/e (relative intensity) 314 (31), 286 (13), 253 (10), 245 (6), 229 (6), 217 (19), 179 (13), 129 (12), 115 (23); IR (KBr) 2942, 2855, 2810, 1428, 1277, 1100 cm-1. High resolution mass spectrum: Calcd. for C24H26: 314.20344; Found: 314.20368. 14. Tetraethyl 1,4,5,8-tetrahydroanthracene-1,4:5,8-diendox- ide-2,3,6,7-tetracarboxy1ate (87). In a procedure similar to that used for 73, reaction of 40 (0.68 g, 3.57 mmol) with diethyl 3,4-furandicarboxylate43 (1.52 g, 7.14 mmol) in dry THF (200 mL) and LTA (3.4 g, 7.67 mmol) gave a yellow solid. Chromatography of the crude product on silica gel with 1:1 ethyl acetatezpetroleum ether gave 0.71 g (40%) of a single bis-adduct (87); mp 188-190°C (after recrystal- lization from ethyl acetate); 1H NMR (250 MHz, CDC13) 5 7.45 (s, 2H), 5.90 (s, 4H), 4.30 (q, 8H, ,1 = 7 Hz), 1,35 (t, 12H, ,1 = 7Hz); 13C NMR (CDC13) 5162.50, 151.31, 146.52, 85 115.76, 85.18, 61.54, 14.07; mass spectrum, m/g (relative intensity) 498 (20), 425 (7), 381 (51), 350 (91), 328 (30), 254 (100), 226 (45), 158 (27), 139 (27); IR (KBr) 2983, 1695, 1628, 1465, 1442, 1395, 1290, 1215, 1125 cm'l. High resolution mass spectrum: Calcd. for C26H26010: 498.15258. Found: 498.15282. 15. Tetraethyl 1,4,5,8-tetramethy1-1,4,5,8,-tetrahydroan- thracene-l,4:5,8-diendoxide-2,3,6,7-tetracarboxylate (89). In a procedure similar to that used for 73 reaction of 40 (0.65 g, 3.42 mmol) with diethyl 2,5-dimethylfuran-3,4-di- carboxylate44 (1.642 g, 6.84 mmol) in dry THF (100 mL) and LTA (3.34 g, 7.52 mmol) gave a yellow residue. Flash chromatography of this crude product over silica gel with, 1:1 chloroformzhexane as eluent gave 1.26 g (67%) of one isomeric bis-adduct (89). An analytical sample was obtained by recrystallization from ethyl acetate; cOlorless needles, mp 233-236°C; 1H NMR (250 MHz, CDC13) 5 7.19 (s, 2H), 4.18 (q, 8H, 4 = 7 Hz), 11.95 (s, 12H), 1.29 (t, 12H, 4 = 7 Hz); 130 NMR (CDCl3) 5 163.00, 153.14, 149.81, 112.91, 112.32, 61.36, 61.24, 14.02; mass spectrum, m/g (relative intensity) 554 (10), 512 (9), 466 (8), 378 (41), 310 (5), 296 (28), 267 (9), 214 (16), 43 (100); IR (KBr) 2990, 2940, 1700, 1628, 1445, 1385, 1370, 1310, 1260, 1145 cm-1. Angl. Calcd. for C30H34010: C, 64.97; H, 6.18. Found: C, 64.86;.H, 6.15. 86 16. Dimethyl 1,4,5,8-tetrahydroanthracene-l,4:5,8-diendox- ide-1,5-dicarboxylate (91). In a procedure similar to that used for 73, reaction of 40 (1.0 g, 5.26 mmol) with methyl 2-furoate43 (1.46 g, 11.6_mmol) in dry THF (100 mL) and LTA (5.13 g, 11.6 mmol) gave a crude product which was triturated with pentane (10 mL) followed by ether (20 mL). The residue was then chromatographed over silica gel (1:3 ethyl acetatezhexane) to give 0.8 g (47%) of a pure product (91). Recrystallization from ethyl acetate gave an analytical sample; white crystals, mp 240-242°C, 1H INMR (250 MHz, CDCl3) 5 7.35) (s, 2H), 7.10 (s, 'vinyl H), 7.08 (5, vinyl H), 5.74 (s, bridgehead H), 4.07 (s, 6H); 13C NMR (CD013) 25168.05, 147.07, 144.05, 142.84, 113.96, 96.11, 82.47, 66.05, 52.82; mass spectrum, ye (relative intensity) 326 (29), 300 (25), 274 (15), 239 (25), 213 (100), 179 (34), 152 (43), 126 (15); IR (KBr) 3130, 3095, 3040, 2960, 1760,.1445, 1350, 1200, 1150 cm-1. An_a_l_. Calcd. for C13H1406: C, 66.26; H, 4.32. Found: C, 66.23; H, 4.40. 17. Aromatization of dimethyl 1,4,5,8-tetrahydroanthra- cene-1 , 4: 5 , 8-diendoxide-1 , 5-dicarboxylate (91) . Diepoxide 91 (0.21 g, 0.648 mmol) dissolved in ethanol (50 mL) was hydrogenated in the presence of 10% Pd/C (20 mg) for 2 h and the catalyst was filtered. The resulting solution was refluxed with cone. HCl (3 mL) for 12 h and cooled to room temperature. The reaction mixture was poured into 87 water (500 mL), extracted with methylene chloride (3 X 50 mL), washed with saturated aqueous sodium bicarbonate solution (3 X 100 mL), dried (MgSO4) and concentrated in vacuo to yield 0.22 g (96%) of the transesterified product 93. The diethyl ester 93 (0.22 g, 0.614 mnol) was treated with conc. HCl (3 mL) in acetic anhydride (30 mL) and reflux- ed for 2 h to afford 0.17 g (81%) of diethyl anthracene-1,5- dicarboxylate 94 as a yellow s011d: mp 185°C [lit.46 185°C); 250 MHz 1H NMR (CDC13) £59.67 (s, 2 H), 8.31 (m, 2H), 7.50 (m, 47), 4.53 (q, 4 H,.i = 7 Hz), 1.51 (t, 6 H,.i = 7 Hz). 18. Dimethyl 2,3-dipheny1-3-hydroxy-2,3-dihydrofuran-4,5-di- carboxylate (97). Benzoin (8.60 g, 40.5 mmol) and 6.9 g (48.6 mmol) of dimethyl acetylenedicarboxylate were heated at reflux for 20 h in 150 mL of acetone containing 5 g of potassium carbonate. The mixture was cooled, poured onto ice, and extracted with methylene chloride. The mixture was dried and the solvent evaporated to yield 6.2 g (40%) of crude solid which was recrystallized from methanol; white crystals, mp 116°C (lit.47 116-117°C); 1H NMR (CDC13) €57.4-7.0 (m, 10H), 4.0 (s, 3H), 3.6 (s, 3H), 3.0 (s, 1H). 19. Dimethyl. 4,5-diphenylfuran-2,3-dicarboxy1ate' (98). The dihydrofuran 97 (5 g, 14.1 mmol) from above was refluxed for l h in 200 mL of methanol containing 1 mL of conc. sulfuric acid and the mixture was poured onto ice and extracted three times with 30-mL portions of methylene chloride. The combined extracts were washed twice with 88 50-mL portions of saturated sodium bicarbonate solution, once with 50 mL of saturated sodium chloride solution and dried over anhydrous magnesium sulfate. Removal of the solvent yielded 4.25 g (85%) of 98, which was recrystallized from methanol, white crystals, mp 87-89°C (lit/17 87-89°C); 1H NMR (CDC13) 5 7.39-7.29 (m, 10H), 3.95 (s, 3H), 3.77 (s, 3H). 20. Tetramethyl 3,4,7,8-tetraphenyl-1,4,5,8-tetrahydroan- thracene-1,4:5,8-diendoxide-1,2,5,6-tetracarboxylate (99). The procedure was similar to that used for 73 except that the reaction was carried out at reflux. Reaction of 40 (0.4 g, 2.1 mmol) with dimethyl 4,5-dipheny1furan-2,3-dicar- boxylate“ (1.41 g, 4.2 mmol) in dry THF (100 mL) and LTA (2.05 g, 4.62 mmol) gave a crude product. Recrystallization from chloroform afforded 1.22 g (78%) of one isomeric bis-ad- duct (99) as colorless needles, mp 283-287°C; 1H NMR (250 MHz, CD013) 58.11 (s, 2H), 7.45-7.l (m, 20H), 3.97 (s, 6H), 3.61 (s, 6H); 13C NMR (not available because of poor solubility); mass spectrum, ,m/§_ (relative intensity) 746 (trace), 586 (5), 426 (28), 129 (29), 105 (100); IR (KBr) 3060, 2960, 1775 (C=O), 1725 (C=O), 1445, 1343, 1205, 1165, 1029 cm'l. Angi. Calcd. for C46H34010: C, 73.99; H, 4,59. Found: C, 73.79; H, 4.70. In this experiment when the reaction was carried out at room temperature, no trace (of bis-adduct was observed and the diene used as the trapping agent was recovered quantitatively. 89 21. 2,6-Dibromo-1,4,5,8-tetrahydroanthracene-1,4:5,8-dien- doxide (101). In a procedure similar to that used for 73, reaction of 40 (0.92 g, 4.842 mmol) with 3-bromofuran43 (1.565 g, 10.6 mmol) in dry THF (100 mL) and LTA (5.15 g, 11.6 mmol) gave, after the usual workup, a grey residue. Recrystallization of this crude product from chloroform afforded 1,23 g (69%) of a single bis-adduct; white crystals, mp 115°C (decomposition); 18 NMR (250 MHz, CDC13) 57.32 (s, 2H), 6.96 (d, 2H, ,1 = 2 Hz), 5.69 (broad s, 2H), 5.38 (d, 2H, 11 = 2 Hz); 13C NMR (not available because of the poor solubility of the product); mass spectrum, mflg (relative intensity) 368 (20), 289 (7), 287 (6), 262 (14), 180 (37), 152 (100), 126 (16); IR (KBr) 3090, 3020, 1573, 1335, 1237, 1210, 1122, 1028, 985 cm‘l. 11:111. Calcd. for C14HgBr202: C, 45.69; H, 2.19. Found: C, 45.55; H, 2.27. 22. Bis-[2-lethy1-3-pheny1-2,3-d1hydro]ben20[1,2-d:4,5-d']di- isoxazole (107). In a procedure similar to that used for 73, reaction of 40 (0.504 g, 2.653 mmol) with N-methyl- asphenylnitrone49 (0.717 g, 5.306 mmol) in dry THF (100 mL) and LTA (2.6 g, 5.86 mmol) gave a yellow solid. This solid was-flash chromatographed on silica gel (3:1 ethyl acetate:hexane), yielding one pure bis-adduct (107), 0.83 g, 91%). An analytical sample was obtained by preparative TLC on silica gel (1:1 ethyl acetate:hexane); white crystals, mp 142-143°C; 1H NMR (250 mHz, CDC13) 5 7.38'- 7.33 (m, phenyl 10H), 6.42 (s, central aromatic 2H), 5.04 (s, benzylic 28), 2.94 (s, N-methyl 6H); 13C NMR (CDC13) 6 151.05, 129.88 90 (overlap), 128.62, 128.26, 127.82, 103.53, 77.00, 45.94; mass spectrum, .m[g (relative intensity) 344 (100), 329 (31), 314 (83), 286 (24), 267 (49), 115 (63); IR (KBr) 3095, 3040, 2965, 2880, 2830, 1460, 1340, 1165, 1145 cm'l. £11811. Calcd for C22H20N202: C, 76.72; H, 5.85; N, 8.13. Found: C, 76.79; H, 5.85; N, 8.10. 23. N-lethyl-(1-2,4,6-trimethy1phenylnitrone (108). Freshly distilled mesitylaldehyde (10 g, 67.56 mmol) was added to a 250-mL round-bottomed flask containing N-methylhydroxylamine hydrochloride (7.05, 8.44 mmol) in methylene chloride (150 mL). Sodium bicarbonate (20 g, 238 mmol) was added to the flask, and the reaction mixture was refluxed for 12 h. When the mixture cooled, the sodium bicarbonate was filtered and washed with methylene chloride, and the solvent was removed at reduced pressure to yield 11 g (92%) of crude product (108). Recrystallization from ethyl acetate gave pure product: mp 172-173°C: 18 NMR (250 MHz, CDC13) 5 7.50 (s, vinyl, 1 H), 6.84 (s, aromatic, 2 H), 3.82 (s, N-CH3, 3H), 2.24 (s, 3 H), 2.26 (s, 68); 13C NMR (CDC13) 6138.82, 136.99, 135.08, 127.93, 125.46, 52.77, 20.71, 19.36; mass spectrum, m/e (relative intensity) 177 (9), 162 (100), 145 (24), 115 (10); IR (KBr) 3080, 2910, 1570, 1440, 1410, 1395, 1370, 1180, 1038 cm-1. m1. Calcd. for C11H15NO: C, 132.12; H, 15.12;‘N, 14.01. Found: C, 74.41; H, 8.78; N, 7.81. 24. Bis-[2-Iethyl-3-(2',4',6'-trimethylpheny1)-2,3-dihydro]- benzo[1,2-d:4,5-d']diisoxazole (109). In a procedure similar 91 to that used for 73, reaction of 40 (0.227 g, 1.194 mmol) with N-methyl-a—(2,4,6-trimethylpheny1)-nitrone 108 (0.42 g, 2.388 mmol) in dry THF (50 mL) and LTA (1.16 g, 2.616 mmol) gave a crude product which was flash chromatographed on silica gel (3:2 etherzchloroform) to provide 0.40 g (78%).of 109 (single isomer); white solid, mp 239-241°C; 1H NMR (250 MHz, CDC13) 6 6.85 (s, mesityl 4H), 6.14 (5, central aromatic 2H), 5.66 (s, benzylic 2H), 2.96 (s, N-meth- yl 6H), 2.30 (broad s, 12H), 2.27 (s, 6H); 13C NMR (CDCl3) <5 151.22, 141.70, 139.05, 138.05, 130.12, 130.09, 129.17, 101.38, 72.59, 46.45, 20,83; mass spectrum, 19./.9. (relative intensity) 428 (100), 413 (10), 384 (84), 309 (19), 160 (3), 133 (21); IR (KBr) 3010, 2960, 2920, 2860, 1610, 1475, 1440, 1315, 1160 cm’l. High resolution mass spectrum: Calcd. for C28H32N202: 428.24636; Found: 428.23901. 25. Attempted synthesis of 1,4-dimethy1—1,4,5,8-tetrahy- droanthracene-l,4:5,8-d1endoxide (110). To a stirred mixture of 40 (0.29 g, 1.5 mmol) and 2,5-dimethylfuran (0.1447 g, 1.5 mmol) (in 75 mL of dry tetrahydrofuran was added in portions LTA (0.665 g, 1.5 mmol) suspended in 30 mL of THF at room temperature for a period of 30 min. 'Upon completion of the addition of LTA, furan (0.102 g, 1.5 mmol) was added to the reaction mixture followed by addition of LTA (0.665 g, 1.5 mmol) in 30 mL of dry THF over 30 min. The reaction mixture was stirred for an additional 10 min, and the lead diacetate was filtered. The filtrate was diluted with 500 mL of water and extracted with three 92 100-mL portions of chloroform. The combined extracts were washed once with 50 mL of saturated sodium bicarbonate solution and dried over anhydrous magnesium sulfate. Removal of the solvent in vacuo affordedoa yellow oil which was chromatographed on a silica gel using 2:1 chloroformzbenzene as eluent. The first fraction, 0.12 g was 1,4,5,8-tetrameth- yl-l,4,5,8-tetrahydroanthracene-1,4:5,8-diendoxide (73). The second fraction, 0.11 g was 1,4,5,8-tetrahydroanthracene-1,4: 5,8-diendoxide (71). 26. Reaction of 40 with one equivalent of 2,5-dimethylfuran and one equivalent of lead tetraacetate (LTA). To a stirred mixture of 40 (0.37 g, 1.947 mmol) and 2,5-dimethylfuran (0.187 g, 1.947 mmol) in 100 mL of dry THF at room tempera- ture was added in portions LTA (0.86 g, 1.947 mmol) suspended in dry THF (20 mL) over 30 min. After 10 min additional stirring, lead diacetate was removed by. filtration. The filtrate was diluted with 500 mL of water and extracted with three 280-mL portions of chloroform. The combined extracts were washed once with saturated aqueous sodium bicarbonate solution and dried over anhydrous magnesium sulfate. Removal of the solvent gave a crude product which was chromatographed on silica gel using 1:1 chloroform:ether as eluent to afford 0.18 g (70%) of 73: mp 229°C (decomp) 18 NMR (250 MHz, CDCl3) 6 6.96 (s, aromatic), 6.78 (8, minor, vinyl), 6.76 (s, major, vinyl), 1.87 (8, major, methyl), 1.86 (s, minor, methyl). 93 27. Attempted reaction of 1-amino-benzo[1,2-d:4,5-d']-bis- triazole 64, with 2,5-dimethylfuran and lead tetraaCe- tate. To a stirred mixture of 1-amino-benzo[l,2-d:4,5-d']- bistriazole 64 (0.3 g, 1.71 mmol) and 2,5-dimethylfuran (0.8 g, 8.32 mmol) in 150 mL of dry THF at reflux under argon was added lead tetraacetate (1.67 g, 1.71 mmol) in portions over 30 min. After the usual work-up, removal of the solvent left a tan residue shown by 1H NMR to be unreacted 64. 28. 1,3,3,4,7,8-Hexamethyl-5,6-bis(z,Z-cyanomethylene)-bi- cyclo[2.2.2]oct-7-en-2-one (116). To a mixture of 0.62 g (3.263 mmol) of 1,6-diamino-benzo [1,2-d:4,5-d']bistri- azole, 63, and 0.58 g (3.258 mmol) of 2,3,4,5,6,6-hexamethyl- cyclohexa-2,4-dienone 9 in 100 mL of dry tetrahydrofuran (THF) at room temperature was added in portions 3.2 g (7.21 mmol) of lead tetraacetate (LTA) in 50 mL of dry THF over a period of 30 min. After 5 min additional stirring, the lead diacetate was filtered, the filtrate was diluted with 500 mL of water and extracted three times with 100-mL por- tions of methylene chloride. The combined extracts were washed with saturated aqueous sodium bicarbonate solution, saturated aqueous sodium chloride solution and dried over anhydrous magnesium sulfate. The solvent was removed in vacuo and the residue was chromatographed on silica gel using 3:1 chloroform:hexane as eluent to afford 0.74 g (81%) of 116 as a white solid, mp 368-369°C; 18 NMR (250 MHz, CDCl;,) 65.66 (s, 1H, vinyl), 5.62 (s, 18, vinyl), 94 1.77 (s, 3H, 1 = 1H2), 1.70 (s, 3H, ._J_ = 182), 1.46 (s, 3H), 1.41 (s, 38), 1.09 (s, 38), 0.89 (s, 38); 13C NMR (CDC13) 5 199.50 (C=O), 161.28, 155.75, 139.52, 129.98, 116.54, 115.87, 98.06, 96.13 (six vinyl and two nitrile carbons), 60.06, 52.24, 45.71 (three quaternary carbons), 23.58 (overlap), 14.25, 13.90, 11.99, 11.62 (six methyl carbons); mass spectrum, m/g (relative intensity) 280 (trace), 210 (100, M+-dimethylketene), 237 (1), 195 (17), 183 (9),) 168 (10), 153 (4); IR CKBr) 3025, 2970, 2930, 2870, 2215 (CN), 1740 (C=O), 1590, 1440, 1385, 1270 cm-1- High resolution mass spectrum: Calcd. for C18H20N20: 280.1575; Found: 280.1582. 29 . Reaction of 1 , 6-diamino-benzo[1 , 2-d : 4 , 5-d ' ]bistria- zole 63 with two equivalents of lead tetraacetate. To a stirred mixture of 1,6-diamino-benzo[1,2-d:4,5-d']bistria- zole 63 (0.56 g, 2.95 mmol) in 100 mL'of dry THF under argon was added lead tetraacetate (2.9 g, 6.5 mmol) in portions over 30 min. After the usual workup, removal of the solvent gave only 0.17 g of a polymeric oil. 30. Reaction of 1,5-diamino-benzo[1,2-d:4,5-—d']bistriazole 40 with one equivalent of lead tetraacetate. Lead tetra- acetate (0.7 g, 1.58 mmol) in 30 mL of dry THF was added over 20 min in portions to a stirred suspension of 40 (0.3 g, 1.58 mmol) in 50 mL THF under argon at room temperature. The solvent was removed under reduced pressure and washing of the brown residue with water left only a polymeric powder. No desired product could be isolated from the residue. 95 31. Reaction of 1,5-diamino-benzo[l,2-d:4,5-d']bistriazole 40 with lead tetraacetate in the presence of 1,1-dimethoxy- ethylene. Lead tetraacetate (3.1 g, 6.95 mmol) in 50 mL of dry THF was added over 30 min in portions to a stirred suspension of 40 (0.6 g, 3.16 mmol) and 1,1-dimethoxyethyl- ene53 (0.62 g, 6.95 mmol) in 100 mL THF under argon at room temperature. Lead diacetate formed was removed by filtration. A work up sample of the reaction mixture indi- cated the presence of the unreacted olefin (0.57 g, 95% recovery). 32 . 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8-Octapheny1anthracene (125) . In a procedure similar to that used for 73, reaction of 40 (0.018 g, 0.0947 mmol) with 1,2,3,4-tetraphenylcyclOpentadienone (0.0728 g, 0.190 mmol) in refluxing THF (300 mL) and LTA (0.093 g, 0.21 mmol) gave a crude product. Recrystallization from benzene gave 0.041 g (56%) of 125 as a yellow solid, mp 415-417°C; 18 NMR (250 MHz, d6-DMSO, 110°C)57.33 (s, 2H), 7.1-6.7 (m,- 40H); mass spectrum, 111/g (relative intensity) 786 (71), 105 (9), 44 (100); IR (KBr) 3080, 3055, 3030, 1595, 1490, 1443, 1032 cm’l- High resolution mass spectrum. Calcd for C62H42: 786.3284. Found: 786.33130 33 . Tetramethyl 2 , 3 , 6 , 7-tetraphenylanthracene-1 , 4 , 5 , 8-te— tracarboxylate (128). In a procedure similar to that used for 73, reaction of 40 (0.2 g, 1.052 mmol) with 2,5-me- thoxycarbonyl-a,4-dipheny1cyclopentadienone54 (0.732 g, ‘ 2.10 mmol) in dry THF (50 mL) and LTA (1.026 g, 2.31 mmol) gave a grey product. Flash chromatography over silica 96 gel eluting with 2:1 chloroform:hexane yielded 0.70 g (93%) of 128 which was recrystallized from ethyl acetate to give yellow crystals, mp 375-376°C; 18 NMR (250 MHz, CDC13) 68.55 (s, 28), 7.25-7.07 (m, 208), 3.65 (s, 12H); 13C NMR (CDC13) (5 168.75, 138.37, 138.13, 133.37, 130.40, 129.99, 128.34, 126.66, 52.11; mass spectrum, m/_e_ (relative intensi- ty) 714 (100), 683 (1), 619 (3), 504 (5), 476 (8), 325 (48), 237 (38); IR (KBr) 3060, 3025, 2950, 1721, 1434, 1360, 1226, 1092, 1041 cm-1. 1&1. Calcd. for C46H3403: C, 77.30; H, 4.79. Found: C, 77.33; H, 4.88. 34. Bis-(N-methyl)-1,2,3,4,5,6,7,8-octaphenyl-1,4,5,8-tetra— hydroanthracene-1,4:5,8-bisimine (130). In a procedure similar to that used for 73, reaction of 40 (0.3078 g, 1.62 mmol) with N-methyl-z,3,4,5-tetrapheny1pyrro1e40 (1.25 g, 3.24 mmol) in dry THF (100 mL) and LTA (1.58 g, 3,56 mmol) gave a yellow product which (was recrystallized from benzene to yield 1.2 g (88%) of a single isomer (130); white solid, mp 205-207°C; 18 NMR (250 MHz, CDCl3) 8 7.8-6.6 (m), 2.12 (broad s); 13C NMR (CD013) 8 134.58, 131.37, 130.98, 128.46, 128.07, 127.66, 127.31, 127.03, 126.96, 126.85, 126.62, 77.14, 31.46; mass spectrum, 181/2 (relative intensity) 844 (M+, not shown), 399 (3), 385 (8), 178 (100); IR (KBr) 3060, 3030, 2950, 1605, 1485, .1443, 1325, 1290, 1155 cm'1. Anal. Calcd for C64H48N2: C, 90.96; H, 5.72; N, 3.31. Found: C, 90.85; H, 5.70; N, 3.25. 97 35. 1,4,5,8-Tetraphenyl-1,4,5,8-tetrahydroanthracene-1,4:5,- 8-diendoxide (133). In a procedure similar to that used for 73, reaction of 40 (0.293 g, 1.54 mmol) with 2,5-di- phenylfuran (0.678 g, 3.08 mmol) in dry THF (100 mL) and LTA (1.50 g, 3.38 mmol) gave a crude product. Preparative TLC on silica gel using 4:1 benzenezhexane as the eluent yielded 0.59 g (75%) of 133 as a pale yellow solid. Although the melting point was fairly sharp, the 13C NMR analysis showed some minor extraneous peaks; mp 264-265°C; 1H1NMR (250 MHz, CDC13)6‘7.67-7.25 (m, 228), 6.74 (s, 48); 13C NMR (CDC13) 5151.02, 146.24, 144.49, 135.61, 128.70, 126.93, 113.42, 93.53; mass (spectrum, 111/2 (relative intensity) 514 (100), 498 (18), 105 (18); IR (KBr) 3035, 1605, 1495, 1450, 1425, 1350, 1105, 985 cm’l. .Agg1. Calcd. for C38H2602: C, 88.69; H, 5.09. Found: C, 88.58; H, 5.08. 36. 5,7,12,14-Tetraphenyl-5,7,12,14-tetrahydropentacene-5,- 14:7,12-diendoxide (140). In a procedure similar to that used for 73, reaction of 40 (0.097 g, 0.51 mmol) with l,3-diphenylisobenzofuran (0.276 g, 1.02 mmol) in THF (40 mL) and LTA (0.5 g , 1.12 mmol) gave a crude product'which was recrystallized from ethyl acetate/hexane to yield 0.28 g (88%) of a pure product (140); white crystals, mp 306-308°C; 18 NMR (250 MHz, CDC13) 6 8.2-6 85 (m); 13C NMR (CDC13)5149.22, 134.85, 128.80, 128.43, 126.61, 125.68, 120.36, 113.49, 113.29, 90.50; mass spectrum, m/_e_ (relative intensity) 614 (41), 493 (19), 404 (45), 105 (100), 77 (15); IR (KBr) 3065, 3040, 1600, 1495, 1450, 1425, 1340, 98 1312 cm-1. Anal. Calcd. for C46H3002: C, 89.88, H, 4.92. Found: C, 89.76; H, 4.85. 37. 5,7,12,14-Tetraphenylpentacene (141). A dry 500 mL three-necked flask, oven-dried, :equipped with a rubber septum, a magnetic stirring bar, a dropping funnel, and a reflux condenser connected to a bubbler, was under argon. The flask was covered with aluminum foil to avoid light. To a suspension of 9.0 mL (excess) of titanium tetrachloride in 200 mL of freshly distilled tetrahydrofuran at 0°C was added 10.0 g of zinc powder (excess). The steel grey suspen- sion was heated to reflux, and a solution of bis-epoxide (140) (1.8 g, 2.931 mmol) in 50 mL of THF was added dropwise over 10 min. The mixture was refluxed for 16 h, then cooled to room temperature, and poured into! dilute hydrochloric acid. The resulting deep-blue mixture was extracted twice with 100-mL portions of methylene chloride. The combined extracts were washed three times with 100-mL portions of saturated aqueous sodium bicarbonate solution, dried over anhydrous magnesium sulfate, and concentrated in vacuo to afford the crude product (all the work-up was performed in a dark hood as quickly as possible). This crude product was triturated with ethanol (20 mL) and filtered to give 1.38 g (81%) of 141 as a violet solid, mp 410-411°C (lit.56 411°C); 18 NMR (250 MHz, CDC13) 88.21 (s, 2H), 7.68-7.64 (AA', 4H), 7.43-7.26 (m, 208), 7.18-7.13 (BB', 48); 13C NMR (CDCl3) 6138.72, 131.28, 130.31,129.11, 128.78, 128.08, 127.09, 125.87, 124.80, 124.60; mass spectrum, 111/Q (relative 99 intensity) 582 (100), 507 (31), 426 (13), 303 (14), 291 (85), 253 (87), 244 (48), 231 (19), 214 (98), 207 (36) 38. Dimethyl 5,7,12,14-tetraphenyl-6,13-dihydro-6,13-etheno— pentacene-5,16.-dicarboxylate (151). A 250-mL three-necked flask was fitted with a septum, a magnetic stirring bar, a dropping funnel, and a condenser topped by an argon bubbler connection. The flask was covered with aluminum foil up to the necks to avoid light. To a stirred solution of 0.644 g (1.107 mmol) of 5,7,12,14-tetraphenylpentacene (141) in 50 mL of dry THF was added 0.157 g (1.107 mmol) of dimethyl acetylenedicarboxylate in 50 mL of THF through a dropping funnel over 10 min. The resulting solution was refluxed for 5 h, then cooled to room temperature. The reaction mixture was poured into water (200 mL) and the cloudy aqueous layer ‘was extracted three times with 30-mL portions of methylene chloride. The combined extracts were washed twice with 50-mL portions of a saturated aqueous sodium bicarbonate solution, once with a saturated aqueous sodium chloride solution and dried over anhydrous magnesium sulfate. After removal of the solvent, the grey solid was flash chromatographed on a silica gel column and eluted with 1:1 chloroformzbenzene to give 0.68 g (85%) of 151 as a white solid. An analytical sample was recrystallized from ethanol, mp 375-376°C; 18 NMR (250 MHz, CDCl3) 8 7.5 (AA', 4H), 7.4-7.2 (m, 20H), 7.13 (BB', 4H), 5.58 (s, 2H), 3.74 (s, 68); 13C NMR (CDC13) 5 146.90, 130.14, 137.02, 130.93, 130.52, 130.40, 128.16, 127.94, 127.19, 126.60, 100 125.68, 52.06, 47.12; mass spectrum, 311/; (relative intensity) 724 (100), 605 (45), 582 (52), 302 (78), 263 (48), 250 (20), 213 (22); IR (KBr) 3050, 3020, 2940, 1715 (C=O), 1630, 1592, 1485, 1432, 1370, 1325, 1260, 1230 cm‘lo 4221- Calcd. for C52H36O4: C, 86.17; H, 5.00. Found: C, 85.94; H, 5.15. 39. 5,7,12,14-Tetraphenyl-6,13-dihydro-6,13-ethanopentacene- 15,16-dicarboxylic anhydride (153). This Diels-Alder adduct was prepared by the reaction of 5,7,12,14-tetraphenyl pentacene 141 (0.484 g, 0.8314 mmol) and maleic anhydride 152 (0.0815 g, 0.8314 mmol) in dry THF as in the preparation of Diels-Alder adduct 151. The crude product was triturated with ethanol (2 X 20 mL) to give 0.26 g (46%) of 153 as a white solid. The melting point was checked in a sealed capillary tube. At 75°C, the compound turned slowly to blue and at 200 °C, complete blue solution was formed. It seems that the. compound undergoes a retro Diels-Alder reaction on heating. 18 NMR (250 MHz, CDC13) 8 7.45-6.95 (m, 28H), 5.06 (d, _.1 = 1.2 Hz, 2H), 3.52 (d, 1 = 1.2 Hz, 2H); 13C NMR (not available because of poor solubility); mass spectrum, .m/§_ (relative intensity) 680 (not shown), 582 (25), 507 (3), 426 (2), 291 (26), 253 (15), 244 (20), 213 (14), 44 (100); IR (KBr) 3050, 3020, 1766, 1490, 1440, 1373, 1225, 1070, 1030, 925 cm‘l- PART II . ACID-CATALYZ- AND PHOTOCHEIICAL REARRANGEIENTS OF NOVEL KETONES 101 102 Introduction In part II of this thesis, the structure determination of adduct 102 (page 48), obtained from the reaction of DABT- LTA sun! 2,3,4,5,6,6-hexamethylcyclohexa-2,4-dien-1-one, is presented. Also, the acid-catalyzed and photochemical rear- rangements of this and a related ketone and epoxy ketone are described. 103 Results and Discussion A. Structure of the Bis-adduct Obtained From the Reaction of Hexamethyl-2,4-cyclohexadienone 9 and DABTLTA. Hart and Gray prepared the adduct 1116 by the reaction of 2,3,4,5,- 6 , 6-hexamethylcyclohexa-2 , 4-dien-1-one 960 with benzyne generated from benzene diazonium 2-carboxylate. The 1H NMR spectrum of this adduct showed two methyl groups at 60.47and 1.06 (syn “and anti-3-methyls), a six-proton signal at 5 1.62 (bridgehead methyls), and two mutually coupled (11 = 1 Hz) methyl signals (allylic methyl) at 6 1.82 and 1.74. Dienone 9 was subjected to reaction with 40 and LTA to give an analogous bis-adduct 102, (79% yield), mp 338°C (decomp), which appeared to be one of the four possible regioisomers (154-157) as shown. Compound 102 gave the correct analysis and its 250. MHz 1H NMR spectrum showed a sharp singlet for the two aromatic protons at 6 7.00, two homoallylic methyl signals (A = 1 Hz) at 6 1.78 and 1.69, and four methyl singlets at 51.67, 1.62, 1.07 and 104 Pb(OAc), 40 + flBis-adduct /\ I \ \y / 155 157 0.49. On the basis of the 1H NMR data, two posssible struc- tures, 156 and 157 can .be excluded because they would be expected to show two different aromatic proton signals. The 13C NMR spectrum showed fifteen bands, also consistent with either structure 154 or 155. The infrared spectrum had a carbonyl band at 1710 cm“1 and a strong carbon-carbon double bond absorption at 1600 cm'l. Unfortunately, these 105 spectral data do not afford enough information to tell whether the bis-adduct is 154 or 155. From the viewpoint of product development control, structure 154: is ,preferred since the molecule may have a natural tendency to reduce its dipole moment. The ultimate structure proof for the bis-adduct must be provided by a single crystal X-ray diffraction study which is in progress. For convenience, structure 154 will be used in this discussion. In connection with the NMR methyl peak assignment of the bis-adduct, it was useful to synthesize trideutero-Q, labeled at C-3 (158) and hexadeutero-Q, labeled at C-3 and C-5 (159). These labeled dienones were prepared accord- ing to Hart and coworkers as shown below.64 CH,OD . _ 1’ 011,0 Ne DC 9 158 t-auo'K’l ouso-d, 158 > [%C [h 106 Reaction of dienones, 158 and 159 separately with DABT-LTA provided the corresponding bis-adducts 160 and 161. The 250 MHz 18 NMR spectrum of the dg-bis-adduct 160 was identical with that of 154 except that the methyl proton CD, 1.87 (1 o,c % 0’ $9 03 1.78 1J8 160 161 signal at 6 1.69 was absent and the peak at 1.78 was unsplit. The _d_12-bis-adduct 161 had a singlet for the two aromatic protons at 6 7.00 and four sharp methyl singlets at 8 1.78, 1.67, 1.07 and 0.49 in its 250 MHz 18 NMR spectrum. Consequently, the 1H NMR signals of 154 were assigned as indicated in the figure. 0 1.67 l I 0.49 (syn) 1.01(antv 1.69(Quartet) l 1.18 (Quartet (J 154 ) The mass spectrum of 154 showed a small parent peak 107 at .m[§ 430 (relative intensity 1), a weak fragmentation peak at m/g 360 (M+-dimethylketene) and a base peak at m/g 290 (M+-two dimethylketenes). In fact, the: mass spectrum of 154 was very similar to that of compound 16265 indicating that it easily loses two dimethylketene species on electron impact. 162 B. Acid-catalyzed Rearrangement of 1,3,3,4,7,8,10,12,12,13- 16,17-nodecamethy1-henzoll,2-e:4,5-e']hisbicyclol2.2.2]oct-5,7- diene-2,11-dione (154). The rearrangement of , -unsaturated ketones in acid66 has considerable potential for the synthesis of unusual b1- and tricyclic ring systems. In most examples described thus far, however, the double bond is present in a relatively strained cyclobutene ring. For example, the isomerization 163 -—§ 164 was reported to be nearly quantitative; the mixture resulting from heating 163 in benzene containing TsOH contained 92.5% of 164 and 7.5% of recovered 16367. Theser data, reflect that 163 and 164 are equilibrated by acid and the equilibrium mixture contains 108 1L 164 163 ) 90% of 164. The greater stability of 164 may result from the removal of a 1,3-methyl-methyl interaction. When the [3 ,7 unsaturation is incorporated into an aro- matic ring, aryl and/or alkyl migrations may be observed, as shown below.68‘69 The examples here are illustrative; numerous other examples are presented in Fry's review.7O %1@<.H.Lm '*. Ph P11 A ‘f" t ——:5 (DH — o A >vg *— . P . h 109 The tetralone 165 is converted into 166 by the action of Lewis acids such as aluminum chloride, ferric chloride, and hydrogen fluoride. Ketone 166 undergoes further isomer- ization to yield 167. The course of these changes is outlined in Scheme 6.71 Scheme 6 O O. 0. °‘ ._>.. __~. v- v- 165 +OE O O. ——: O. \__ 166 OE o *0: 0 0e 4... .1 167 Hart and Love discovered a more complex series of isomer- izations of 6,7-unsaturated ketones contained in bicyclo- [2.2.2]- and bicyclo[3.2.1]octane systems.72 For example, when ketone 11 was refluxed with trifluoroacetic acid (TFA) for several hours, an equilibrium mixture of 11 and 168-170 110 was obtained in the amounts shown. A possible mechanism - W "b —-—> 11 (7%) + 168 (28%) 85:3 dr 169 (59 7.) 1 70 (6 7.) for the isomerization which explains the formation of 168 before 169 is shown in Schemes 7 and 8. Isomerization of 11 to 168 involves vinyl, alkyl and aryl migrations. The acid-catalyzed interconversion of 171 and 172 occurs similarly. Scheme 7 111 Scheme 8 O 5"'“,:21§‘»¢E—- Hy" 9' Ph-shfit (flnmmfr” 170 O . . 0 Z/‘ 4—2 Z S 171 172 The closely related rearrangement of 173 to 174 and 175 was also reported.73 173 174 (48 Z) 175 (40%) 112 Since diketone 154 was readily available from the bis-- aryne studies (p. 104) it was thought of interest to study its acid-catalyzed rearrangement. This ketone is the first molecule in that contains the same (3,7 -unsaturated ketOne moieties twice, and thus the outcome of the rearrangement might be quite interesting. The acid-catalyzed rearrangement of ketone 154 in neat TFA afforded after 21 h an equilibrium mixture of four 'iso- meric ketones (176-179), with some minor unknowns (8%). These structures have been arbitrarily numbered in what is thought to be the order of their formation during the reaction. The ratio of isomers was obtained from integra- tion of the aromatic region (GS-6.7) of the crude quenched sample. Tables 7 and 8 list the NMR spectra (1H and 13C) of each of these ketones. All methyl group signals in Table 7 appear as sharp singlets with the exception of those labeled with an asterisk; these show a small (ca. 1 Hz) splitting typical of adjacent methyl groups on a carbon-carbon double bonds. It turned out that the diketones 176 and 177, with no symmetry, were predominant when equilibrium was established. The structure determination of ketones 176-179 follows from their spectra and deuterium labeling experiments when necessary. Both ketones 178 and 179 have a center of inver- sion (point group Ci) whereas ketones 176 and 177 do not. Thus, it is very clear from the 1H NMR spectra whether the ketone is symmetric or not since there will be only one 113 154 1 76 (48 78) 9° ° 178 (15 x) 114 Table 7. 1H NMR spectra of diketones (154, 176-179). Compound Aromatic Methyl mp(°C) 154 .00 .78*,1.69*,1.67 338(decomp) .62,1.07,0.49 176 .64 .88*,1.6l*,1.44(overlap) 256-257 .90 .37(overlap) .23,l.l4,l.01(overlap) .78,0.71 177 .88 .53,1.46,1.43 248-249 .83 .30,1.25,1.22 .17,1.15,1.03 .98,0.72,0.41 178 .77 .45*,1.44*,1.30 313-314 .16,1.03,0.73 179 .74 .86*1.61,1.31 335-336 .29,0.99,0.77 115 me.m .me.e me.m .mm.m mo.nHH .mm.mme oo.oH .mm.HH om.mmH .mm.mms mo.me .mm.mH oo.me .mm.me mm.omH .mm.HmH om.eH .mm.eH mH.me .mm.mm me.mmH .mm.mes mm.HmH mm.Hm .mm.mm mm.em .se.mm em.cva .om.evH Hm.ems use me.m .mo.oH .mm.os Annsso>oc oe.mHH .ee.mHH em.HH .om.mH me.mmH .mm.mm~ mm.ms .om.os me.mm .ee.cm me.HmH .Hc.eefi 98.6H .mm.eH mm.en .mm.mm eo.mvH .em.meH mm.em~ mH.Hm .me.Hm 64.56 .mm.mm mm.m¢a .mm.emH mm.mms one mH.mH mm.mH oe.m4H mo.mH .om.mH mH.me oo.mmH mm.mmH em.mm .4H.em «5.6m .me.mo em.oeH .os.mvs Hm.mmH «ma H1399: unannoudg Hunt, can Quads—0.3 occaou 6:509:00 .Ameaucee .vmev mosoeoxao we assumed msz omH .6 dance 116 Aomsao>ov em.HH mm.cHH mm.mH .oe.oH ee.mm oH.mmH .ec.mv~ mm.cH .mm.sm em.mm .mm.mc mm.omH .om.emH . mm.mmH med me.m .Ho.oH om.HmH oe.HH .mm.mH ma.mn em.omH .cm.mmH mm.eH .em.HN Hm.em .en.cm mm.evs .vm.msH oo.emH and H.399: P395983 Hunt, can owed—no.3 anon—on 6:559:00 .eozseesoo Ameeucea .vmuv monopoxso so mseooem msz one .m dunes 117 band for the aromatic protons if the structure is symmetric. The chemical shifts of the aromatic protons in 178 and 179 should be quite different from one another. Apparently, the protons in 178 are substantially deshielded by the car— bonyl group alpha to the benzene ring. The 250 MHz 1H NMR spectrum of 178 showed a sharp singlet for the two aromatic protons at 6 7.77, two coupled allylic methyl groups ( 6 1.45, 1.44; 1 = 1 Hz) and four other methyl singlets. The 13C spectrum of 178 had fifteen signals as required by symmetry. The infrared spectrum of 178 showed carbonyl absorptions at 1670 cm‘1 (KBr). The enone 178 is yellow, with an absorption maximum at 239 nm (€==2100). The infrared spectrum of 179 showed the expected carbonyl band at 1650 cm“1 (lower frequency than 178) and the ultravio- let spectrum, with the maximum at 240 nm (6:2200), was also consistent with the structure. The aromatic proton signal in the 1H NMR spectrum of 179 can be compared with that of 178. Since the signal occurs at higher field in 179 (66.74) than in 178 ( 6 7.77), it was concluded that the carbonyl group in 179 is not conjugated with the aromatic ring. Since compound 179 is a (conjugated enone, base-catalyzed labeling of 179 should occur only at the C-4 and C-11 methyls. Treatment of 179) at room temper- ature with CH3OD and approximately one equivalent of sodium gave the same dienone 180; in this case, the C-4 and C-11 allylic methyls were labeled as judged by the absence of the peak at 51.86. Also, as expected the peak at 5 1.61 had sharpened to a singlet. 118 The structure differentiation of 176 from 177 was mainly based on their infrared spectra and labeling experiments. The infrared spectrum of 176 had a strong absorption at 1655 cm"1 due to two conjugated carbonyl groups. On the other hand, compound 177 showed two carbonyl bands at 1720 and 1670 'cm‘l, respectively. Enone 176, when treated with Na/CH3OD, gave the trideuterio compound 181 which lacked the low field methyl signal at 61.88. It may be suggested that compound 182 is a possible structure which can be assigned instead of 177. In order 119 to assign the structure 177 with certainty, it was felt necessary to examine its spectra, especially 13C and mass spectrum, more closely. The 13C NMR spectrum of 177 had ten aromatic and vinyl and six quaternary carbon signals confirming structure 177 . Further evidence supporting structure 177 came from its mass spectrum. It showed a- parent peak at m/e 430, a base peak at m/e 415 (IF-methyl) and a major fragmentation peak at mfig 360 (M+-dimethylketene). Loss of a ketene moiety was found to be typical for this type of structure as discussed in the previous chapter. Lei DO 1 d The same equilibrium mixture was obtained when each of the rearranged ketones was separately subjected to the isomerization conditions. Since the same equilibrium mixture was obtained from all four ketones (176-179), the steps must be reversible. 120 C. Photoisomerization of 1,3,4,5,8,8,10,11,12,14,17,17-Dode- camethyl benzo[1,2-f:4,5-f']bisbicyclol3.2.1]oct-3,11-dien-2,- 14-dione (179). Bicyclo[3.2.1]octadienones of .type 183 have been shown to photoisomerize to ketene 184. The ketenes were detected by low-temperature infrared spectroscopy, and in all but the first example by trapping with a nucleophile. In the absence of a nucleophile, ketenes 184 recyclize to 183 or dimerize.75 " o A 17 // 183 184 X = has been an electron pair,74 or a CH2, CH=CH,75 o-C6H4, or EtOZCNNCOZEt75 group) Hart and Love demonstrated that ketene 184 (X = CH2), when completely substituted with methyl groups, reacts differ- ently from its unsubstituted analogs.77 It neither reacts with nucleophiles nor recyclizes to 183, but undergoes a facile intramolecular [2 + 2] cycloaddition. Thus, irradia- tion of 185 (1% solution in methanol, Pyrex) gave the tetra- cyclic structure 186 in 100% yield. The photOproduct 186 isomerizes thermally to 185 in carbon tetrachloride at 100°C with a half-life of 50 min. 121 186 However, the corresponding 3,4-benzooctadienones 187 were shown to undergo reversible 1,3-acyl shifts (187 $5 188).75 The other possible (i.e., 7,8-)benzoderivatives of 187 underwent a facile photoisomerization.79 Ketones of the general structure 168 can be regarded as 4-arylcyclo- hexenones, compounds whose photochemistry has been extensively studied.80'81 187 188 Rearrangement of 168 to 170 was studied with labeled 168 (the label is designated by an asterisk in the mechanistic scheme 9 shown below) and concluded to be an aryl migration mechanism. 122 Scheme 9 123 In a continued effort to explore the scope of the photoisomerization reaction described, as well as the synthesis of the interesting ring system which it generates, compound 179 was investigated. A degassed solution of 179 in spectroscopic grade ace- tone, on irradiation for 12 h through a Pyrex filter using a 450 watt Hanovia lamp, gave virtually pure photoproduct 189 contaminated with less than 2% of starting dienone 179. However, when the reaction was monitored by 1H NMR after 3th, only partial rearrangement (< 20%) occurred. The infra- 179 189 h V — 1, nyCX 450 Watt 0/ Hanovia lamp Acetone 12 h red spectrum (of 189 showed the carbonyl absorption at 1715 cm'l, whereas the starting dienone 179 had the band at 1650 cm‘l. The 250 MHz 1H NMR spectrum had a singlet for the two aromatic protons at 6 6.89 and six methyl singlets at 51.48, 1.28, 1.19, 1.14, 0.96 and 0.34. The peak at 6 0.34 was assigned to the syn methyl of the gem-dimethyl group and the signal was shifted to higher field compared to the corresponding ones (0.41 — 0.77) of its isomers (154, 176-179). This is probably due to the shielding effect 124 of the adjacent methyl group in the cyclopropane ring. The 13C NMR spectrum had a peak for the carbonyl carbon at 5 199.03, three aromatic carbon peaks at .6 136.87, 136.12 and 117.59, five quaternary carbon peaks at 6 54.70, 45.32, 42.07, 39.96 and 35.97 and six methyl peaks at 6 23.00, 17.65, 13.13, 9.96, 7.83, and 5.60. It was suspected that the dienone 179 on irradiation might lead to complicated products unlike its mono-analog 168 since chromophores of new species generated would require different energies for further conversion. Photoisomerization of general structure 168 appears to be quite interesting in affording a single product in excellent yield. D. Photodecarbonylation of syn-7,8-syn-16,17-diepoxy-1,3,3, 4,7,8,10,12,12,13,16,17-dodecamethyl-benzo[1,2-e:4,5-e'] bisbicyclo[2.2.2]oct-2,11-dione (199). Ligerature Backggound When an epoxy function is located 5, ‘7 to a carbonyl group, a Norrish type I mechanism satisfactorily rationalizes the photoproducts. The chemistry of the initially-formed acyl alkyl diradical is dominated by cleavage of the fi-carbon oxygen bond; the resulting acyl alkoxy diradical undergoes competitive reactions shown in Scheme 10.85 125 Scheme 10 423415.. 5.8: Decerbonylet Ion 0 €640 H T v \ There are two routes for lactone formation in path B, direct closure of the acyl alkoxy diradical or disproportiona- tion to a hydroxy ketene followed by intramolecular trapping. For example:83 i—h—b Ether ®+ HC—(CH,)3-g-/>-. (65 z) (10%) An attempt to understand the A vs. B competition has been made by comparison of the behavior of two diastereomeric 126 fi;Y-epoxy ketones.84 The observation was that only fi-oxygen- carbon bond breaking occurs.84 In addition, we note the possibility that disproportiona- tion of the acyl alkyl diradical could be a source of decar- bonylation product. Since the present work involves photodecarbonylation of BfY-diepoxy ketones, literature survey follows, on that tOpic. Chambers and Marples have investigated the photodecarbon- ylation of a steroidalf3-,7-epoxy ketone.85 Irradiation of an ethereal solution of the 9a,1008epoxy-6-ketone 190 in the absence of oxygen resulted in the formation of unsat- urated. epoxide 191 (20%) and lB-nor epoxide 192 (3%), and several minor products. CIHI'I 127 Hart and coworkers have studied. the jphotochemistry .of a family of;3,7-epoxy ketones which also undergo photodecar- bonylation to provide unsaturated,epoxides.86 These reactions proceeded in high chemical yield and by a mechanism clearly different from that reported by (Chambers and Marples for the decarbonylation of 190. Treatment (xf hexamethylbenzobicyclo[Z.2.2]octadienone 11 with m-chloroperbenzoic acid gave the endo epoxy ketone 193. The geometry of the epoxide oxygen was established as endo from 1H NMR chemical shifts, and the difference in chemical shifts, of the methyls at C-7 and C-8.86 m-CPBA a 193 Irradiation of an ether solution of 193 through a Corex filter with a Hanovia L 450-W lamp afforded unsaturated epoxide 194 in ca. 95% yield. 193 ’ 128 An analogous photodecarbonylation occurs with the tetra- methylepoxy ketone 195 to give 196 in 75% yield. However, irradiation of acetone solutions. of epoxy ketone 193 or hV 195 through Pyrex resulted in a much slower rate of disap- pearance of the epoxy ketone, and the formation of complex reaction mixtures. Chambers and Marples have concluded from labeling studies that the diradical 197 provides 191 by two hydrogen migra- tions, C-7 -.-—-> C-5 and C-8 --—-> C-7 (overall a formal 1,4-hydrogen shift), which may be consecutive in this order or synchronous.85 However, this mechanism does not account for the formation of 194 from 193 and 196 from 195. Ostensib- ly, 194 and 196 result from diradical 198 following formal 129 68,0 197 198 1,6-hydrogen shifts. Thus it is apparent that the Chambers and Marples mechanism is not an exclusive route for the photodecarbonylation of 3,7-epoxy ketones. Results ggd Discussion We have studied the photochemistry of symmetrical B,7-di- epoxy ketone 199, which was readily prepared (mp 308-309°C, 85% ‘yield) by the reaction of 154' and. m-chloroperbenzoic acid. The 250 MHz 1H NMR spectrum of 199 consisted of a “i mCPBA RT / 2411 154 130 singlet at 6.90 for the two aromatic protons and six methyl singlets at 5 1.62, 1.56, 1.44, 1.32, 1.16 and 0.65, indicating it was a single isomer. The 13C NMR spectrum showed a peak for the carbonyl carbon at 5 194.21, three aromatic carbon signals at 8 140.63, 133.64, and 116.99 and five quaternary carbon signals at 5 62.71, 59.36, 57.06, 48.49, and. 47.12 and. six: methyl carbon. peaks at 5 24.35, 22.54, 15.98, 13.21, 12.50 and 11.92, as required. by its Ci symmetry. The. infrared spectrum of 199 show/ed a strong carbonyl band at 1720 cm‘l. Deuterated analogs (200 and 201) of 199 were prepared in a similar fashion from the corresponding diketones (160 and 161). 200 A 72 h irradiation of ‘a benzene solution of 199 through Pyrex (Hanovia 450-W lamp) gave unsaturated epoxide 202 131 in quantitative yield. The 250 MHz 1H NMR spectrum. of 202 (mp 222-223°C) showed a singlet at 5 6.94 for the aromatic hV Benzene 450-w lamp 72 h 199 202 protons, two vinyl multiplets at 5 5.09 and 4.79, a quartet at 5 2.98 (i = 7 Hz) for the benzylic protons, a doublet at 5 1.41 for the benzylic methyls, and four methyl singlets at 5 1.56, 1.45 and 1.28 (overlap), as expected from the assigned structure. The infrared spectrum of 202 showed no carbonyl absorption. When 200 (labeled with CD3 at C7 and C16) was irradiated, the methyl signal at 5 1.45 was absent in the NMR spectrum of the product 203. When 201 (labeled with CD3 at C4, C7, C13 and C16) was used, the signals at 5 1.45 and 1.56 were absent in the 18 NMR of the product 204. This evidence permited an unambiguous 132 assignment of structures 202 to the photoproduct from 199. 'l" J-“ 2.98(q, 1:711!) H (14181.1:781) \ “ 1.45 The photoproducts obtained from 199-201 are readily accounted for by the earlier mechanism proposed by Hart and coworkers. 133 figperimental 1. 1,3,3,4,7,8,10,12,12,13,16,17-Dodecamethy1-benzo[1,2-e: 4,5-e']bisbicyclo[2.2.2]oct-7,16-dien-2,11-dione (154). In a procedure similar to that used for 73, reaction of 40 (1.1 g, 5.78 mmol) with 2,3,4,5,6,6-hexamethyl-cyclohexa- 2,4-dien-l-one (2.06 g, 11.57 mmol) in dry THF (200 mL) and LTA (5.65 g, 12.73 mmol) gave a yellow residue which was flash chromatographed over silica gel (1:1 ethyl ace- tate:hexane) to afford 1.95 g (79%) of a single bis-ad- duct. An analytical sample was obtained by recrystallization from ethanol, mp 338°C (decomposition); 18 NMR (250 MHz, CDCl3) 5 7.00 (s, aromatic, 2H), 1.78 (d, C8 and C17-CH3, 1 = 1 Hz, 6H), 1.69 (d, C7'and C16-CH3, 1.1 = 1 Hz, 6H), 1.67 (8, C1 and Clo—CH3, 6H), 1.62 (S, C4 and C13-CH3, 6H), 1.07 (5, C3 and Clz-CH3, anti, 6H), 0.49 (3, C3 and C12-CH3, syn, 6H); 13C NMR (CDCl3) 8 195.51 (C=0), 143.16, 140.34, 138.28, 132.00, 115.40 (three aromatic and two vinyl C), 58.42, 50.42, 45.19 (three quaternary C), 24.14, 23.54, 15.30, 13.08, 12.56, 12.18 '(six methyl c); mass spectrum, m[g (relative intensity) 430 (1), 360 (10, M+-di- methylketene), 290 (100, M+-twoi dimethylketene), 275 (9), 260 (3), 215 (1), 70 (23); IR (KBr) 2980, 2940, 1710, 1600, 1585, 1460, 1440, 1386, 1265 cm-1. 1111. Calcd. for C30H3302: C, 83.67; H, 8.89. Found: C, 83.59; 8, 8.79. 134 2. 2,4,5,6,6-Pentamethyl-3-methyl-d3-2,4-cyclohexadienone (158) . 64 2 , 3 , 4 , 5 , 6 , 6-Hexamethyl-2 , 4-cyclohexadienone (4g) was dissolved in 20 mL of methanol-d containing ~0.3 g of sodium. Monitoring the solution by examination of its NMR spectrum showed that the methyl signal at 5 2.05 disap- peared in less than 10 min at room temperature. No further change in the NMR spectrum occurred after several hours. The trideuterio dienone was isolated by pouring the solution into 400 mL of methylene chloride and washing with three 25-mL portions of ice water. Any residual base was removed with solid C02. The solution was dried over MgSO4 and concentrated to a yellow oil, which was purified by distil- lation on a spinning-band column, yielding 3.3 g (83%) of 158, bp 82-84°C (1.7 mm Hg) (lit.64 100-105°C at 2 mm Hg). A forerun boiling at a lower temperature was rejected. 18 NMR (250 MHz, CDC13) 81.86 (s, 6H), 1.85 (s, 3H), 1.11 (s, 6H). 3. 2,4,6,6-Tetramethyl-3,5-dimethyl-d6-2,4-cyclohexadienone (159). C3-Trideuterated dienone (2.3 g) was added to a solution of 0.68 g of potassium t-butoxide in 12. mL of dimethyl sulfoxide-dg. The NMR spectrum of the solution changed during 6 h at room temperature. The red-brown solution was poured into 600 mL of methylene chloride and worked up in the usual way. The product was purified by distillation on a spinning-band column to yield 2.0 g (87%) of 159, 68-70°C (0.2 mm Hg). 18 NMR (250 MHz, CDCl3)6 1.87 (S, allylic methyl, 3H), 1.83 (S, allylic methyl, 3H), 135 1.13 (s, gem-dimethyl, 6H). 4. 1,3,3,4,8,10,12,12,13,17-Decamethyl-7,16-dimethyl-d6-benzo [1,2-e:4,5-e']bisbicyclo[2.2.2]oct-7,16-dien-2,1l-dione (160). In a procedure similar to that used for 73, reaction of 40 (0.2 g, 1.05 mmol) with 2,4,5,6,6-pentamethyl-3-meth- yl-d3-2,4-cyclohexadienone (0.381 g, 2.1 mmol) in dry THF (40 mL) and LTA (0.886 g, 2.2 mmol) gave a yellow solid. Recrystallization of this crude product from ethyl acetate afforded 0.33 g (76%) of a, pure isomer; white needles, mp 331°C (decomposition); 18 NMR (250 MHz, CDCl3) 8 7.00 (s, aromatic 2H), 1.78 (s, C3 and C17-CH3), 1.67 (8,01 and Clo-CH3), 1.62 (8, C4 and C13-CH3), 1.07 (8, C3 and C12-CH3, anti, 6H), 0.49 (s, (x; and Clz-CH3, syn 6H); mass spectrum (CI), .m[§_ (relative intensity) 436 (91), 435 (100), 364 (19), 295 (7), 281 (8). High resolution. mass spectrum: 'Calcd- for C30H32D602: 436.32483. Found: 436.32471. 5 . 1 , 3 , 3 , 8 , 10 , 12 , 12 , 17-Octamethy1-4 , 7 , 13 , 16-tetramethy1-d12- benzo[1,2-e:4,5-d']bisbicyclo[2.2.2]oct-7,16-dien-2,11-dione (161).. In a procedure similar to that used for 73, reaction- of 40 (0.030 g, 0.1578 mmol) with 2,4,6,6-tetramethyl-3,5-di- methyl-d6-2,4-cyclohexadienone (0.058 g, 0.3157 mmol) in dry THF (25 mL) and LTA (0.154 g, 0.347 mmol) gave a grey solid. Recrystallization of the crude product from ethyl acetate yielded 0.051 g (75%) of a pure isomer; white needles, mp 327°C (decomposition); 1H NMR (250 MHz, CDCl3) 5 7.00 (s, aromatic 2H), 1.78 (s, C8 and C17-CH3), 1.67 136 (8, C1 and Clo-CH3, 6H), 1.07 (s, C3 and Clg-CH3, anti, 6H), 0.49 (s, C3 and C12-CH3, syn, 6H); mass spectrum, m/§_ (relative intensity) 442 (M+, trace), 372 (8, M+-dimethylketene), 302 (100, Mf-two dimethylketene), 70 (29). High resolution mass spectrum: Calcd. for C30H26D1202: 442.36249. Found: 442.36263. 6. Acid-catalyzed rearrangement of ketone 154. Ketone 154 (500 mg) was refluxed in neat TFA (50 mL) for 21 h and cooled to room temperature. The reaction mixture was poured into ice water and then extracted with three 100-mL portions of methylene chloride. The combined extracts were washed with three 50-mL portions of saturated aqueous sodium bicarbonate solution, dried over anhydrous magnesium sulfate and evaporated to dryness to provide rearranged products (176-179) and some unknowns. The ratio of isomers (176:177:178:179:48:20:15:9) was determined from integration of the aromatic region (<586v6.7). The crude product mixture was chromatographed on a silica gel preparative TLC plate with 4:1 chloroform:hexane (five developments) to afford 69.5 mg of 178, 38 mg of 179, 207.5 mg of 176 and 90 mg of 179 along with some unknown products. Analytical samples of 176 through 179 were obtained by recrystallization from ethanol. For 1,5,6,7,8,8,10,11,12,14,17,17-Dodecamethyl-benzo [1,2-c:4,5-f']bisbicyclo[3.2.1]oct-6,11-dien-2,13-dione»(176): mp 256-257°C, white solid; 18 NMR (250 MHz, CDCl3) 8 7.64 (s, 1H), 6.90 (s, 1H), 1.88 (d, 1 = le, 3H), 1.61 (d, ,1 = 1H2, 3H), 1.44 (s, overlap, 6H), 1.37 (s, overlap,6H), 1.23 (s, 3H), 1.14 (s, 3H), 1.01 (s, overlap, 68), 0.78 137 (s, 3H), 0.71 (s, 38); 13C NMR (CDCl3) 8 198.39 (C=O), 197.39 (C=O), 157.95, 149.93, 149.34, 148.04, 147.61, 131.45, 129.38, 125.45, 119.77, 118.70 (ten (aromatic and vinyl C), 66.52, 64.46, 62.32, 57.33, 56.47, 55.48 (six quaternary C), 21.72, 21.15, 17.92, 16.74, 16.36, 13.26, 12.50, 11.34 (overlap), 10.66, 10.06, 9.76 (twelve methyl C); mass spec- trum m/e (relative intensity) 430 (23), 415 (100), 387 (4), 360 (3), 345 (5), 237 (3), 179 (3), 165 (4); IR (KBr) 2970, 2930, 2887, 1655 (C=O), 1600, 1430, 1380, 1280, 1213, 1195 cm‘l; .UV (CHC13) )(max 246 nm (6:2700). High resolution mass spectrum: Calcd. for C30H3302: 430.28716; Found: 430.28717. For 1,5,6,7,8,8,10,11,11,13,16,17-Dodecamethyl- benzo[1,2-c:4,5-e']bicyclo[3.2.1]oct-bicyclo[2.2.2]oct-6,16- dien-2,12-dione (177): mp 248-249°C; 1H NMR (250 MHz, CDCl3) 6 7.88 (S, 1H), 6.83 (s, 1H), 1.53 (8, 3H), 1.46 (S, 3H), 1.43 (S, 3h), 1.30 (S, 3H), 1.25 (S, 3H), 1.22 (S, 3H), 1.17 (5, SH), 1.15 (8, 3H), 1.03 (S, 3H), 0.98 (s, 3H), 0.72 (s, 3H), 0.41 (s, 38); 13C NMR (CDCl3) 5197.21(C=O), 191.25 (C=O), 147.66, 146.84, 142.28, 136.78, 131.32, 130.86, 129.23, 128.80, 122.53, 117.03 (ten aromatic and Vinyl C), 66.47, 57.29, 55.36, 45.13, 42.25, 42.00 (six quaternary C), 22.96, 21.66, 17.88, 17.26, 13.66, 13.03, 11.29, 10.00, 9.92, 9.73, 7.72, 5.49 (twelve methyl C); mass spectrum, m/g (relative intensity) 430 (28), 415 (100), 360 (16), 330, (4), 275 (6), 149 (28); IR (KBr) 2968, 2930, 1720 (C=O), 1670 (C=O), 1598, 1450, 1380, 1260, 1210 cm‘l. High resolution mass spectrum: Calcd. for 138 C30H3302: 430.28716; Found: 430.28701. For 1,5,6,7,8,8,10- 11,12,13,17,l7-Dodecamethyl-benzo[1,2-c:4,5-c']bisbicyclo[3.2. 1]oct-6 , ll-dien-Z , 14-dione (178): mp 313-314°C , yellow crystals; 18 NMR (250 MHz, CDCl3) 8 7.77 (s, 28) 1.45 (S, 51 = 1, 6H), 1.44 (S, ,1 = 1‘, 6H), 1.30 (S, 6H), 1.16 (s, 68), 1.03 (s, 6H), 0.73 (s, 6H); 13C NMR (CDC13) 8197.00 (C=O), 148.34, 147.22, 132.96, 130.84, 121.90 (five aromatic and vinyl C), 66.77, 57.21, 56.19 (three quaternary.C), 21.57, 17.98, 12.35, 11.40, 10.01, 9.75 (Six methyl C); mass spectrum, m/g (relative intensity) 430 (17), 415 (100), 385 (1), 200 (22); IR (KBr) 2986, 2930, 2875, 1670 (C=O), 1440, 1400, 1376, 1272, 1185, 1158 cm‘l; UV (CDCl3) )(max 239 nm (e=2100). High resolution mass spectrum: Calcd. for C30H3302: 430.28716; Found: 430.28717. For 1,3,4,5,8,8— 10,11,12,14,17,17-Dodecamethy14benzo[l,2-f:4,5-f']bisbicyclo- [3.2.1]oct-3,11-dien-2,13-dione (179): mp 335-336°C, white solid; 18 NMR 250 MHz, CDCl3) 8 6.74 (s, 28), 1.86 (d, ,1 = 1, 68), 1.61 (d, ,1 = 1, 68), 1.31 (s, 6H), 1.29 (s, 6H), 0.99 (s, 68), 0.77 (s, 68); 13C NMR (CDCl3) 5 199.36 (C=O), 157.30, 150.29, 143.64, 125.10, 116.93 (five aromatic and vinyl C), 63.59, 62.34, 55.47 (three quaternary C), 21.26, 16.89, 16.40, 13.29, 11.34 (Overlap) (Six methyl C); mass spectrum, m/g (relative intensity) 430 (100), 415 (78), 387 (18), 361 (10), 265 (7), 251 (3), 97 (84); IR. (KBr) 3010, 2985, 2930, 2875, 1650 (C=O), 1615, 1385, 1320, 1305, 1228 cm'l; UV (CHC13) Amax 240 nm (€==2200). High resolution mass spectrum: Calcd. for 139 C30H3302: 430.28716; Found: 430.29749. 7. 1,3,5,8,8,10,12,14,17,17-Decamethyl-4,11-dimethyl-d6-ben- zo[1 ,2-1 :4 , 5-1' ]bisbicyclo[3.2.1]oct-3, 11-dien-2 , 13-dione (180). The dienone 179 (15 mg) was dissolved in 20 mL of methanol-d containing 0.1 g of sodium and refluxed for 30 h and cooled. The hexadeutero dienone was isolated by pouring the solution into 100 mL of methylene chloride and washing twice with 25 mL of water. Any residual base was removed with solid C02. Removal of the, solvent in vacuo yielded 14 mg (93%) of pure hexadeutero dienone 180. 18 NMR (250 MHz, CDCl3) 56.74(s, 2H), 1.61 (s, 6H), 1.31 (s,6H), 1.29 (s, 6H), 0.99 (S, 6H), 0.77 (S, 6H). 8. 1,5,6,7,8,8,10,12,14,17,17-Undecamethyl-11-methyl-d3-ben- zo[1,2-c:4,5-f']bisbicyclo[3.2.l]oct-6,11-dien-2,13-dione(181). In a procedure similar to that used for 180, reaction of 176 (13 mg) with 0.1 g of sodium in 20 mL of methanol-d gave after work-up pure trideutero dienone; 1H NMR (250 MHz, CDCl3) 5 7.64 (s, 1H), 6.90 (s, 1H), 1.61 (s, 3H), 1.44 (s, overlap, 6H), 1.37 (s, overlap, 6H), 1.23 (s, 3H), 1.14 (s, 3H), 1.01 (s, overlap, 6H), 0.78 (s, 3H), 0.71 (s, 3H). 9. The equilibration of ketone 178 in TFA. A 20 mg sample of ketone 178 was refluxed for 21 h in neat TFA and quenched using the procedure outlined in general quenching studies to afford 19 mg of a pale yellow solid. The 1H NMR spectrum of the sample was similar to that of a sample from the 140 rearrangement (21 h reflux) of 154 in TFA. 10. Photoisomerization of 1,3,4,5,8,8,10,11,12,14,17,17-dodeca- methyl-benzo[1,2-f:4,5-f']bisbicyclo[3.2.1]oct-3,11-dien-2,13- dione (179). A degassed solution of 179 (20 mg) in 20 mL of spectroscopic grade acetone was irradiated through a pyrex filter using a 450 watt Hanovia lamp for 21h. Removal of the solvent in vacuo gave essentially pure photoproduct 191 contaminated with less than 2% of starting dienone 179; mp 367°C (decomposition), white solid; 1H NMR (250 MHZ, CDCl3) 5 6.89 (s, 2H), 1.48 (s, 6H), 1.28 (s, 6H), 1.19 (s, 6H), 1.14 (s, 68), 0.96 (s, 6H), 0.34 (s, 68); 13C NMR (CDCl3) 5 199.03 (C=O), 136.87, 136.12, 117.59 (three aromatic C), 54.70, 45.32, 42.07, 39.96, 35.97 (five quaternary C), 23.00, 17.65, 13.13, 9.96, 7.83, 5.60 (six methyl C); mass spectrum, .m/e (relative intensity) 430 (100), 415 (84), 387 (16), 361 (12), 333 (11), 303 (10), 275 (8), 245 (9), 205 (3), 97 (57); IR (KBr) 2975, 2921, 1715, (C=O), 1460, 1387, 1323, 1270, 1048, 985 cm‘l; High resolution mass spectrum: Calcd. for C30H3802: 430.28716; Fougd: 430.28701. 11. Syn-7,8-syn-l6,l7-diepoxy-l,3,3,4,7,8,10,12,12,13,16,17- dodecamethyl-benzo[1,2-e;4,5-e']bisbicyclo[2,2,2]oct-2,ll-dione (199). A solution of 0.23 g (1.33 mmol) of 85% m-chloroper- benzoic acid in 10 mL of methylene chloride was added during 10 min to an ice-cold stirred solution of 0.22 g (0.511 mmol) of 154 in 20 mL of methylene chloride. Stirring was continued in an ice bath for 1 h and at room temperature 141 for an additional 24 h. Excess peracid was destroyed by the addition of 10% sodium sulfite until a test with starch-iodide paper was negative. The reaction mixture was washed three times with 50 mL of 5% sodium bicarbonate solution, twice with 50 mL of water, and once with 50 mL of saturated sodium chloride solution, and dried over anhydrous magnesium sulfate. Removal of the solvent provided a crude product which. was recrystallized from ethanol to yield of 0.2 g (85%) of a single isomer (199) as white needles: mp 308-309°C; 18 NMR (250 MHz, CDCl3) 8 6.90 (s, aromatic, 2H), 1.62 (S, C1 and Clo—CH3, 6H), 1.56 (S, C4 and C13-CH3, 6H), 1.44 (S, C8 and C17-CH3, 6H), 1.32 (S, C7 and C16-CH3, 6H), 1.16 (s, C3 and Clz-CH3, anti, 6H), 0.65 (3, C3 and 012-C83, syn, 6H); 13C NMR (CDCl3) 8 194.21, (C=O), 140.63, 133.64, 116.99 (three aromatic C), 62.71, 59.36, 57.06, 48.49, 47.12, (five quaternary C), 24.35, 22.54, 15.98, 13.21, 12.50, 11.92 (six methyl C); mass spectrum, m/g (relative intensity) 462 (7), 392 (8), 349 (20), 263 (36), 251 (13), 236 (22), 221 (11), 206 (8), 43 (100); IR (KBr) 2975, 1720, 1463, 1380, 1260, 1093, 1010, 873 cm‘l; UV (CHC13) >‘max 236 (6:1600). High resolution mass spectrum: Calcd. for C30H3304: 462.2770; Found: 462.2778. 12. Syn-7,8-syn-16,17-d1ep0xy-1,3,3,4,8,10,12,12,13,17-deca- methyl-7,16-dimethyl-(u;-benzo[1,2-e:4,5-e']bisbicyclo[2.2.2]- oct-2,11-dione (200). In a procedure similar to that used for 199, reaction of 160 (0.098 g, 0.224 mmol) with 85% ' m-chloroperbenzoic acid gave a crude product which was 142 recrystallized from ethanol to yield 0.089 g (85%) of .a single isomer (200) as white needles: mp 308-309°C; 1H NMR (250 MHz, CDCl3) :5 6.90 (s, aromatic, 2H), 1.62 (s, C1 and Clo-CH3, 6H), 1.56 (S, C4 and C13-CH3 6H), 1.44 (8, C3 and C17-CH3, 6H), 1.16 (s, C3 and Clz-CH3, anti, 6H), 0.65 (8, C3 and Clz-CH3, syn, 6H); mass spectrum, 111/g (rela- tive intensity) 468 (trace), 397 (6), 352 (22), 293 (10), 265 (30), 251 (27), 239 (39), 97 (23)» 43 (100). High resolution mass spectrum: Calcd for C30H32D604: 468.31465. Found: 468.31390. 13. Syn-7,8-syn-16-17-diepoxy-1,3,3,8,10,12,12,17-octamethyl- 4,7,13,16-tetramethyl-d12_benzo[1,2-e:4,5-e']bisbicyclo[2.2.2]- oct-2,11-dione (201). In a procedure similar to that used for 199, reaction of 161 (0.024 g, 0.0542 mmol) with 85% m-chloroperbenzoic acid gave a crude product which was recrystallized from ethanol to yield 0.021 g (85%) of a single isomer (201) as white needles: mp 308-309°C; 1H NMR (250 MHz, CDCl3) 8 6.90 (s, aromatic 2H), 1.62 (s, C1 and Clo-CH3, 6H), 1.44 (8, C3 and C17-CH3, 6H), 1.16 (8, C3 and C12-CH3, anti, 6H), 0.65 (8, C3 and C12-CH3, syn, 6H); mass spectrum, _m_/_e_ (relative intensity) 474 (trace), 403 (3), 358 (9), 288 (16), 271 (14), 244 (17), 70 (22), 43 (100). High resolution mass spectrum: Calcd for C30H26D1204: 474.35232; Found: 474.3522. 14. Photolysis of 199. A solution of 20 mg 'of 199 in 20 mL of benzene was irradiated at room temperature with a 143 450-watt Hanovia lamp through a Pyrex filter. Monitoring the photolysis by 250 MHz 18 NMR after 12 h irradiation showed a significant decrease in the concentration of 199 and a progressive increase in the concentration of photoproducts (two sets of vinyl peaks at 6 5.11, 4.81 (minor) and 8 5.09, 4.79 in the 250 MHz 18 NMR). Examination of the photolysis by 250 MHz 1H NMR after irradiation for 72 h indicated the presence of only a single photoproduct 202 which was recrystallized from ethylacetate: mp 222-223°C; 1H'NMR (250 MHz, CDCl3) 8 6.94 (s, 2H), 5.09 (m, 28), 4.79 (m, 2H), 2.98 (q, i = 7Hz, 2H), 1.56 (s, 6H), 1.45 (s, 6H), 1.41 (d, 1 = 7 Hz, 6H), 1.28 (s,12H);mass spectrum, m/g (relative intensity) 406 (2), 363 (3), 149 (16), 95 (17), 43 (100); IR (KBr) 3094, 2981, 2947, 1512, 1464, 1380, 1266 cm‘l. High resolution mass spectrum: Calcd. for C23H3802: 406.28716; Found: 406,28735. 10. Soc . 1975, 144 References For a review see, Hoffmann, R. W. "Dehydrobenzene and Cycloalkynes” Academic Press, New York, 1967. Bryce, M. 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Chem. 1973, 33;, 3805. 152 .Aowv Aem¢nv mHONmfiHumwnm.olm.¢nolm.Haonoonlo:HSmHQIm.H Mo maz ma am: omm .H F N n v m o n m a. _C- _LL:_- C-; L c L. c L l 131W. % l 1 «:4 A O 2 153 .Aowv Aem L +LL1— .Afiev maonafippmfinm.eun.v”num.Haouamnuoafieafinus.fi mo mzz mH us: can .m N n V m _ o h m m -- ---?p-+--L--LL_L., k.r»rrb---+--- -p--y--x»-,LL_.-r}, --_-rLL ---,b,-- , ,_,- 413:1, Aafi .1“ £2 1.86 .AH¢V OHONmfihumwnm.Uim.quIN.Haoucmnloawadfinlh.fi mo mzz OmH .v o o m 8. on. a L b b b \— r b L L L— b b L L b h L b - l‘.‘ 1 1 i’ P 1 1' II D.” F), l I J 11 1—1 11“ 14414 411 ll 4 11141411.! GOP Omw 155 156 .Amov maouafiupmflnfl.oun.euoum.HHonamn-o=HaaHoum.H mo mzz ma um: omm .m o P a n v m o s m a L . - :L ,,,,,,,,, _F_L__+_ ...... .:_tt::._: 4 5! 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L DL _ LLLLL'D 1% LL L11 L15 LL 171 .Amnnv moflnoznoa ofifihxonuwofio smH.mfinoaoompamaoaaspwumfi.mLogosnflanH.m-~m:mng«ppmeuvfi.mfl.s.m Ho mzz ma um: 0mm .om o F u n e m o A o a 1 1 1 1 1 1 p 1 1 1 J LJL T 172 .1wmflv maofiouflfl.mnamHoLmH.snpoomm.m.m1odosofin . a a a a a a a g a N oHN :mHQH.msm.enmum.H1ouamnuasnuosaooooousa.mH ma «H «H oH m s v m m H mo mzz ma a: cam o F N n V m o h a w L 1 1 LL LL 1L L L1 LL 1 LL L L1 L L.1 L L 1|L11fi1¢414 fiLL 173 .18mav ouoficuafl.muamficnmfi.supoomm.m.m1 _ofiosofinmflnm.m-m.vuoum.11ounmnuflsnpmaaooeoausfi.oH.mH.mH.mH.oH.m.s.v.m.m.H mo mzz omfi .mm c on co. _ . amp L1 L1 L 1 1 1 LL, 1 LL LL 1 1 ’DPILDII’D" jfi ( 111114 OWN .n to 174 .Acmav maofieuflfi.m-=mfiuumfi.supooam.m.m1oaosofinmfia1.mum.vnm-m.fi1 oucmnuouuasnumefiuuma.sufisnuoeaomousfl.mH.mH.mH.oH.w.v.m.m.H Ho maz ma um: omm .mm LL—bbb — L— b _ — DDLFDL bbbb F hhhh hLi-LPLLL DFDLLLLLD IDDLLDLDI DDDDDDDD’ FL DDDDDD D_DDI5LLILL L>DIDF h—L 1 L 11]] . 11L . 1112.1 "no 175 .AHoHV maownuflfi.muamfiouofi.supooHN.m.m1ofiosoHnmfinm.mum.vnmum.fi1 ouaonumfinnassumsanumpuofl.mH.s.enasapmaawoo-sfi.mfi.NH.oH.w.m.m.H Ho mzz ma as: can .wm b—E—I’LhLDLDL_LLDDIDLLbL—LLLLLLLLDbDLLFPLLD_LLLLIDLLL—LLIDLFLDDhIIDLDLDID—profilIE—I 11w ADELJ . a 176 .Amsfic maofiuumfl.muamfiuufla.mupooHH.N.m1ofiosoan Lm1n1.“no.8”oum.H1ouamnaasnpoaaomuonasa.RH.«H.NH.HH.oH.w.w.s.m.m.H mo maz mfl was com .mm o p u a v m o A a 8 L1 L L1- L L L1LLLLLLLLL1LLL LLLLL1LLLL LLLLPLLLLL LLL1LLLLL LLL1L L LLLL1 LL L1 LLL 'IIIIIIIIJIJ ll‘ Ill 3 11 1 7 177 .Aouflc maoficnmfi.muamficuafl.oupoomfi.m.m1 oHosofinmfinm.mun.vnoum.H1ouconufisnpmaaomoonuufl.sH.¢H.NH.HH.oH.m.m.L.o.m.H Ho maz omH .mm on cop omw OON L L L L b L L L L L L L L L L— L L L L L . 178 .Amuav maofiuuvfi.m-=ofiuufifl.ouuooflfl.m.mHoHo>ofinmfin L.o-m.¢noum.Haounmn-flznpmeaomnoauufl.uH.mH.mH.HH.oH.w.m.u.m.m.H Ho msz mH uz: omm .um 1:4 b fil u n v m o n o m _ _ _ LL -- _ LL x$ _ _ J4 179 .Lmbav oaofinu«fi.muamfiu-afi.mupooLH.m.mL oLoLoHnanL.o-n v oum.HLouamn-LL:pmeaomoonu>H.LH.mH.mH.HH.oH.w.m.u.o.m.H Lo msz omH .mm c on co. on. if L L L L _ L L L L _ L L L L b L L 11...,an 180 .Laufiv maofinuma.munmfioufifi.mupooLH.m.mLoHoLo -fiannL.L1m v mum.HLouconuLanmanmuonnuH.LH.¢H.NH.HH.oH.m.m.m.w.m.H msz ma um: omm o L . a n v m m L m L L» ‘» LN LLL , L L. - L L L L. .mm m L a 3i L7 L]: 181 .meav maoflnlmfi.muamficuflfi.mupooLH.m.mL oLoLoanfinL.m-m.wumum.HLouamnnLanmsaomuoauufi.LH.vH.NH.HH.oH.w.m.m.v.m.H maz umH .om on 009 omp OON L— L L L L L L L F L x— L L L L {P Lo L. L 182 o p N n 1L] ; .me occuox mo msz EH N3: omN .Hm j’.’>’?brr— ’?Db-”bbbr’FLL’P’b'LLbb""b”””’b-bl’bb”b’b’—LLLP\P I4 183 .me chvmx mo maz OmH Omw .Nm 184 .mmH occumx onam mo :22 ma LPLrVLEVLFrErrPDrP-VLLPPFFri—D'IbPDLDb—I?P|rDrpllrrerrlP'rrrr—PLPP?P?LrhrrPr*rr Nma omm .mm LrblhlrtPPLrP—D r ii: 1 w 185 Lo .mmH meopmx axoam Lo maz omH .vm on. LLL LL L L L, LL L LLL 186 .oou maouox onam Lo msz ma was com .nm 187 .Hcm muopmx onam no maz ma was com .mm m o L. o a LL L L LLL L LILLLL -L 1L 188 .Nom mufixoao Lo maz ma an: com .um o L a n v m o L. m m rrL...iIL:_ ......... Li.ZILLLICCEL_LLLLIiLL LLLLLLLLL L LLLLLLLLL LIIILZL LLLLLLLL LLL L.1 L LJJ LL j 4 189 o p N a Q .mca mofixoqm no maz ma an: omm .mm m PLPLLPPLDPr’—>PFFI*L’P—LLLPLLLLFLPFL_7*LFLLL’brk—F’IPLPL’PPL_LPLLDIL??— 1 J1 PP’D j 190 .wou mnfixono Lo maz :H was com .mm o P N n v m 0 h w m Pr—+P>P>L>*r_brrbbPP??—rPPrLDrPP—LPPPLPPP?—DPLLLLLFP—>DP>PPFLLL—PP>rPPPLP>_Prerbbhh_P*bhbprI_Pb L7 L.1 j. 4L M'CITL'I‘LLLEI’LILIIMLLLLIILLLL'LELLEFELLLLL'ILIWL‘L‘IL‘L'“ h.“ ”40%—’7‘ ‘72" ‘*' ' “‘