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ATTEMPTED SYNTHESIS OF A NOVEL CYCLOPHANE presented by LON-TANG WILSON LIN has been accepted towards fulfillment . of the requirements for ; Ph-D- degree in lihemjstny Major professor l l I Date March 10. 1982 MS U is an Affirmative Action/Equal Opportunity Institution 0-12771 PVIESIL] RETURNING MATERIALS: M ace in book drop to LJBRARJES remove this checkout from Q‘ your record. be charged if ook is returned after the date stamped below. PART I THE SYNTHESIS AND REACTIONS OF AROMATIC COMPOUNDS c-FUSED WITH THIOPHENE PART II ATTEMPTED SYNTHESIS OF A NOVEL CYCLOPHANE BY Lon-Tang Wilson Lin A DISSERTATION Submitted to Michigan State University in partial fulfillment of the requirement for the degree of DOCTOR OF PHILOSOPHY Department of Chemistry 1982 I/73’7 _‘ 5 C ABSTRACT PART I THE SYNTHESIS AND REACTIONS OF AROMATIC COMPOUNDS C-FUSED WITH THIOPHENE PART II ATTEMPTED SYNTHESIS OF A NOVEL CYCLOPHANE BY Lon-Tang Wilson Lin I In Part I of this thesis, the synthesis and reactions of aromatic compounds condensed with c-fused thiophene were developed. All of these heterocycles possess one to three thiophene rings surrounding a six-membered carbocyclic ring. To study the effect of methyl subStituents on the benzolclthiophene skeleton, various benzoIclthiophene derivatives such as 4,5,6,7-tetramethylbenzolclthiophene, 57, 1,3-dimethylbenzo[clthiophene 60, 5,6-dimethylbenzo- [clthiopehen’ 74, and hexamethylbenzolclthiophene 65 were synthesized. The methyl substituents on the thiophene moiety in 60 increased its reactivity, whereas compound 57 and 74 with methyl substituents on the benzenoid Lon-Tang Wilson tin moiety, are more stable than benzoEclthiophene. This stability' may' be due to steric effects which slow .down bimolecular reactions. In contrast, the fully' methylated 65 readily dimerized, possibly due to peri-strains. The mechanism by which l,3-dihydrobenzo[clthiophene-Z- oxides are dehydrated by base to the corresponding thio- phenes was investigated. The reaction requires two equiva- lents of base, and proceeds via the dianion. Lithium diiso- propylamide (LDA) functions well as the base. Consistent with the proposed mechanism, 1,4,5,6,7-pentamethylbenzo[c]- thiophene and l-deuterio-4,5,6,7-tetramethylbenzo[c]thio- phene were obtained by reacting 4,5,6,7-tetramethyl-l,3- dihydrobenzo[c]-thiophene-2-oxide with LDA followed by quenching with methyl iodide or MeOD respectively. Naphtho- [1,2-clthiophene 35, naphthol2,3-c]thiophene, phenanthro- [9,lO-c]thiophene 33, and 4,5,6,7,8,9-hexamethylnaphtho [2,3-c]thiophene were synthesized by this novel method. An attempt to trap thieno[3,4-c]thiophene, generated in this way, with dimethyl acetylenedicarbokylate (DMAD) failed, but 2,5-dibromothieno[3,44c1thiophene could be trapped with DMAD. Electrophilic substitution (particularly' bromination) of certain benzo[c]thiophenes was studied. The two phenan- threne analogs benzo[1,2-c:3,4-c'ldithiophene 34 and 35, as well as the triphenylene analogsnaphtho[1,2-c:3,4- c'Jdithiophene, benzo[1,2-c:3,4-c':5,6-c"]trithiophene 30 and 33 were brominated. In,all cases, bromination occurred Lon-Tang Wilson Lin in the thiophene rather than the carbocyclic moiety. A novel reaction occurred in bromination of 33 and 35 with excess N-bromosuccinimide in acetic acid; the initial- ly formed fused-ring 2,5-dibromothiophene was further brominated at an already substituted position to give a dibromothiolactone, which ultimately hydrolyzed to a thio- anhydride. Compound 34 reacted with tetracyanoethylene (TCNE) to form first a charge-transfer (CT) complex and then a Diels-Alder adduct in which TCNE added to both thiophene moieties. Trithiophene 30 formed only a CT complex. In Part II, attempts to synthesize a novel cyclophane in which two naphthalene rings are connected in a loop by having either 1,8-positions linked to the 4 and. 4' po- sitions of two biphenyl moieties are described. l-(4'-Bromo- phenyl)naphthalene 46 and 1,8-bis(4'—halophenyl)naphtha- lenes were prepared. via. the corresponding trimethylsilyl derivatives, through replacement of the trimethylsilyl groups by electrophiles. 4,4'-Bis(l-naphthyl)biphenyl was obtained from 46 by a homocoupling reaction. 4,4'-Bis(8- phenyl-l-naphthyl)biphenyl was isolated from various homo- coupling reactions of l,8-bis(4'-halophenyl)naphthalene with different catalysts. Trace amounts of the desired target cyclophane were isolated which had the correct molecular weight by mass spectrometry, but the amounts were insufficient for unequivocal identification. ACKNOWLEDGMENTS I wish to express my deepest gratitude to Professor Harold Hart for his enthusiasm, advice and guidance through- out the course of this study. Appreciation is extended to Michigan State University, the National Science Foundation, and the National Insti- tutes of Health for financial support in the form of teach- ing and research assistantships. Finally, I thank my parents, my brother and sisters and my wife for their love, support and constant encourage- ment during these years. I also thank ‘my wife for as- sistance in the typing of this thesis. ii TABLE OF CONTENTS Chapter LIST OF TABLES . . . . . . . . . . . . . . . . LIST OF ABBREVIATIONS . . . . . . . . . . . PART I - THE SYNTHESIS AND REACTIONS OF AROMATIC COMPOUNDS c-FUSED WITH THIOPHENE . . . . . . . . . . . . INTRODUCTION . . . . . . . . . . . . . . . . . . . . RESULTS AND DISCUSSION . . . . . . . . . . . . . . . A. SYNTHESIS OF THE DERIVATIVES OF BENZOICITHIOPHENE . . . . . . . . . . . . . 1. Synthesis of 4,5,6,7-Tetramethylbenzo[c]- thiophene 57 O O O O I O O . O O O O O O O O O 2. Synthesis of 1,3-Dimethylbenzo[clthiophene 60 O O O O O I O O 0 O O O 0 O I O O O O O 3. An Approach to the Synthesis of HexamethylbenzoIclthiophene 65 . . . . 4. A Mechanistic Study of the Dehydration of Cyclic Sulfoxides with Base . . . . . . . 5. Synthesis of Hexamethylbenzo[clthiophene 65 B. APPLICATIONS OF LDA AND MeOH TO THE AROMATIZATION OF CYCLIC SULFOXIDES . . . . . 1. Synthesis of 5,6-Dimethylbenzo[c]thiophene 74 and Benzo[c]thiophene 5 with LDA and Methanol . . . . . . . . . . . . . . . 2. Synthesis of Naphtho[1,2-c]thiophene 35 and Naphthol2,3-c]thiophene 76 . . . . . . . iii Page xi 15 15 15 22 24 25 32 33 33 35 Chapter 3. Page Synthesis of 4,5,6,7,8,9-Hexamethyl naphtho[2,3-c]thiophene 83 . . . . . . . . . . 37 4. Synthesis of Phenanthrot9,10-c]thiophene 33 . 39 5. An Attempt to trap Thieno[3,4-c]thiophene l7 . 40 6. Synthesis of 3, 4-Diphenylthiophene 112 from the Sulfoxide lll . . . . . . . . . . . . 46 C. SYNTHESIS AND CHEMISTRY OF BENZO[1,2-c:3,4-c'JDITHIOPHENE 34 AND ITS BROMINATION COMPARED WITH THAT OF NAPHTHO[1,2-CJTHIOPHENE 35 . . . . . . . . . . 47 l. A New Approach to the Synthesis of Benzo[l,2-c:3,4-c']dithiophene 34 . . . . . . 47 2. Bromination, A Typical Electrophilic . Substitution Reaction of 34 . . . . . . . . . 50 3. Synthesis of 7,8-Dibromobenzo[l,2-c:3,4-c'l- dithiophene 130 and its bromination . . . . . 55 4. Metalation of 34 with two molar equivalents Of n-BuLi O O O O O O O O O O O O O O O O 0 0 s7 5. Bromination of Naphtho[1,2-c]thiophene 35 . . 59 D. SYNTHESIS OF NAPHTHOIl,2-c:3,4-c']- DITHIOPHENE 32 AND ITS BROMINATION COMPARED WITH THAT OF BENZOTRITHIOPHENE 30 AND PHENANTHROTHIOPHENE 33 . . . . . . . . 63 1. Synthesis of Naphtho[l,2-c:3,4-c']- dithiophene 32 . . . . . . . . . . . . . . . . 63 2. Bromination of 30, 32 and 33 . . . . . . . . . 64 E. COMPARISON OF THE CHEMICAL REACTIVITY OF 5, 30 AND 34 . . . . . . . . . . . . . . . 69 EXPERIMENTAL . . . . . . . . . . . . . . . . . . ._. . 72 1. General Procedures . . . . . . . . . . . . . . 72 2. 4,5, 6, 7-Tetramethyl-l ,3-dihydrobenzolcl- thiophene (55) . . . . . . . . . . . . . 72 iv Chapter Page 3. 4,5,6,7-Tetramethyl-l,3-dihydrobenzo[c]- thiophene-Z- oxide (56) . . . . . . . . . . . 73 4. 4,5,6,7-Tetramethylbenzolc]thiophene (57) . . 75 S. The adduct of 57 and TCNE . . . . . . . . . . 76 6. l-Methyl-l,3-dihydrobenzolc]thiophene- 2-oxide (58) . . . . . . . . . . . . . . . . . 76 7. 1,3-Dimethyl-1,3-dihydrobenzo[clthiophene- 2-0xide (59) O O O O O O O O O O O O O O O 0 I 77 8. l,3-Dimethy1benzo[clthiophene (60) and its adduct 61 with TCNE . . . . . . . . . . . 78 9. 1,4,5,6,7-PentamethylbenzoIc]thiophene- 2-°x1de (63) O O O O O O O O O O O O O O O O O 79 10. l-Deuterio-4,S,6,7-tetramethylbenzoIcl- thiophene (71) . . . . . . . . . . . . . . . . 80 ll. 1,4,5,6,7-Pentamethylbenzo[clthiophene (72) and its TCNE adduct . . . . . . . . . . . . . 80 12. An attempt to prepare 71 from 57 with LDA and MeOD . . . . . . . . . . . . . . 81 13. Hexamethylbenzo[clthiophene (65) and its TCNE adduct (73) . . . . . . . . . . . . . 82 14. 5,6-Dimethyl-l,3-dihydrobenzo[clthiophene (74b) . . . . . . . . . . . . . . . . . . . . 83 15. 5,6-Dimethyl-l,3-dihydrobenzolclthiophene- 2-oxide (74c) . . . . . . . . . . . . . . . . 84 16. 5,6-Dimethylbenzo[c]thiophene (74) and it TCNE adduct (74d) . . . . . . . . . . . . . 84 17. Benzolclthiophene (5) and its TCNE adduct . . 85 18. Naphtho[l,2-c1thiophene (35) . . . . . . . . . 86 19. Naphtho[2,3-c]thiophene (78) and its TCNE adduct (79) . . . . . . . . . . . . . . . 86 Chapter 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32. 33. 34. 35. 36. 37. Page 4,5,6,7,8,9-Hexamethy1-l,3-dihydronaphtho- [2,3-clthiophene (81) . . . . . . . . . . . . 87 4,5,6,7,8,9-Hexamethyl-l,3-dihydronaphtho- [2,3-clthiophene-2-oxide (82) . . . . . . . . 88 4,5,6,7,8,9-Hexamethylnaphtho[2,3-c1thiophene (83) and its TCNE adducts (84, 85) . . . . . . 88 l,3-Dihydrophenanthro[9,10-c1thiophene (88a) . 89 1,3-Dihydrophenanthro[9,10-clthiophene-Zs oxide (87) O O O O O O O O O O O O O O O O O O 90 Phenanthrot9,10-c1thiophene (33) . . . . . . . 90 3,4-Dibromo-2,5-dihydrothieno[3,4-clthiophene (97) . . . . . . . . . . . . . . . . . . . . . 91 2,5-Dihydrothieno[3,4-clthiophene (96a) . . . 91 2,5-Dihydrothieno[3,4-c1thiophene-l-oxide (96b) 0 O O O O O O O O O O O O I O O O O O O 91 An attempt to trap thieno[3,4-cJthiophene (17) With DMAD O O O O O O O O O O O O O O O O 92 3,4-Dibromo-2,5-dihydrothieno[3,4-cJ- thiophene-l-oxide (98) . . . . . . . . . . . . 93 2,5-Dibromothieno[3,4-clthiophene (99) and dimethyl 1,3-dibromobenzo[c]thiophene- 5,6-dicarboxylate(101) . . . . . . . . . . . . 93 3,4-Diphenylthiophene (112) . . . . . . . . . 94 1,3,4,6-Tetrahydrobenzo[l,2—c:3,4-c'1- dithiophene- 2,5-dioxide (121) . . . . . . . . 94 Benzo[1,2:c-3,4:c'ldithophene (34) . . . . . . 95 Bromination of 34 with bromine . . . . . . . . 96 Bromination of 34 with one equivalent of NBS O O O O O O O O I O O O I O O I O I 0 O O 96 Bromination of 34 with three equivalents Of NBS I O O O O O O O O O O O O O I O O O O O 98 vi Chapter . " Page 38. Bromination of 34 with four equivalents Of NBS O O O O O O O O O O O O O O O O O O O O 98 39. 3,4,5,6-Tetrakis(bromomethyl)—l,2- dibromobenzene (128) . . . . . . . . . . . . . 99 40. 7,8-Dibromobenzo[l,2-c:3,4-c'ldithiophene (130) O O O O O O O O O O O O O I I O O O O O 99 41. Bromination of 130 with four equivalents Of N38 0 O O O O O O O O O O O O O O O O O O O 100 42. 1,6-Diformylbenzo[1,2-c:3,4-c'ldithiophene (135) O O O O O I O O O O O O O O O O O O O O 101 43. Charge-transfer complexes of 34 . . . . . . . 101 44. Adduct of 34 and TCNE . . . . . . . . . . . . 102 45. Bromination of naphtho[1,2-c]thiophene (35) . . . . . . . . . . . . . . . . . . . . . 103 46. Conversion of 142 to 141 . . . . . . . . . . . 105 47. Hydrolysis of 141 to naphthalene-1,2- dicarboxylic acid (141a) . . . . . . . . . . . 105 48. 1,2,3,4-Tetrakis (bromomethyl)naphtha1ene (146) O O O O O O O O O O O O O O O O O O O O 105 49. Naphtho[l,2-c:3,4-c'ldithiophene (32) . . . . 106 50. Bromination of naphtho[1,2-c:3,4-c']- dithiophene (32) . . . . . . . . . . . . . . . 107 51. Bromination of phenanthrot9,10-clthiophene (33) . . . . . . . . . . . . . . . . . . . . . 107 52. Treatment of phenanthro[9,10-clthiophene- 1,3-dibromo (148) with NBS . . . . . . . . . . 108 53. Bromination of benzo[1,2-c:3,4-c':5,6-c"]- trithiophene 30 . . . . . . . . . . . . . . . 109 vii Chapter PART II - ATTEMPTED SYNTHESIS OF A NOVEL CYCLOPHANE . . . . . . . . . . . . . INTRODUCTION 0 O O O O O I O O O O O O O O O O 0 O O A. REVIEW OF SOME CYCLOPHANES . . . . . . . . . 8. REVIEW OF THE SYNTHESIS OF 1,8-DIPHENYLNAPHTHALENE . . . . . . . . RESULTS AND DISCUSSION . . . . . . . . . . . . . . . 1. Synthesis of 1-Phenylnaphthalene 5 as a model system . . . . . . . . . . . . . 2. First Attempt to synthesize 13 . . . . . . 3. Synthesis of 1-(4'-Chloropheny1)naphthalene (41) and 1,8-(di-4'-Chlorophenyl)Naphthalene (42) O O O O O O O O O O O O O O O I O O O 4. Synthesis of l,8-Bis(4'-bromopheny1)- napththalene (45) and 1-(4'-Bromophenyl)- naphthalene (46) . . . . . . . . . . . . . 5. Synthesis of 1-(4'-Bromopheny1)naphthalene 46 and Its Homocoupling Reaction . . . . . 6. Synthesis of 1,8-Bis(4'-halophenyl)- naphthalenes 45 and 55 . . . . . . . . . . . 7. Synthesis of l,8-Bis(4'-halophenyl)- naphthalenes 45 and 55 with Arylzinc Chloride Solution . . . . . . . . . . . 8. Attempts to synthesize 13 . . . . . . . 9. Another Approach . . . . . . . . . . . . EXPERIMENTAL . . . . . . . . . . . . . . . . . . l. l-Phenylnaphthalene (5) . . . 2. l,4-Bis(1'-naphthyl)benzene (39) . . . . 3. Attempt to prepare the di-Grignard reagent from 1,8-diiodonaphthalene and magnesium viii Page 111 112 112 123 131 131 132 133 134 136 138 140 143 150 153 153 154 155 Chapter Page 4. l-(4'-Chloropheny1)naphthalene (41) . . . . . 156 5. l,8-Bis(4'-Chloropheny1)naphthalene (42) . . . 156 6. 1,8-Bis(4'-bromopheny1)naphthalene (45) . . . 157 7. 1-(4'—Bromophenyl)naphthalene (46) . . . . . . 158 8. 1-(4'-Trimethylsilylphenyl)naphthalene (48) . 158 9. 1-(4'-Bromopheny1)naphthalene (46) from the electrophilic bromination of 48 . . . . . 159 10. Dimerization of l—(4'-bromopheny1)naphtha1ene (46) O O O O O O I O O O O O O O O O O O O O O 160 ll. 1,8-Bis(4'-trimethylsilylphenyl)naphthalene (51) . . . . . . . . . . . . . . . . . . . . . 160 12. l,8-Bis(4'-trimethylsilylphenyl)naphthalene (51) from the arylzinc chloride . . . . . . . 161 13. 1,8-Bis(4'-bromopheny1)naphthalene (45) from compound 51 and bromine . . . . . . . . . 162 14. 1,8-Bis(4'-iodopheny1)naphthalene (55) . . . . 162 15. The Di-Grignard Reagent of 55 . . . . . . . . 163 16. Attempt to synthesize 13 from the , di-Grignard reagent 57 . . . . . . .‘. . . . . 164 17. Preparation of 51 from 55 with n-BuLi and trimethylsilyl chloride . . . . . . . . . 166 18. Attempt to dimerize 55 with n-BuLi and CuC12 O O O O O O O O O O O O O O O O O O O O 167 19. Attempt to dimerize 55 with Ni(P 3)3 as catalyst . . . . . . . . . . . . . . . . . 167 20. l,8-Bis(4'-trimethylsilylbiphenyl)- naphthalene (66) and 1-(4'- trimethylsilylbiphenyl)naphthalene (69) . . . 168 BIBLIOGRAPHY OF PART I . . . . . . . . . . . . . . . . 170 BIBLIOGRAPHY OF PART II . . . . . . . . . . . . . . . 174 LIST OF TABLES Table Page 1. % isoindole in CDCl by NMR . . . . . . . . . . 6 3 DDQ DMAD DMF LDA NBS NPMI TCNE TCNQ TMEDA Ni(acac)2 Ni(dppp)2 LIST OF ABBREVIATIONS 2,3-Dichloro-5,6-dicyano-1,4-benzoquinone Dimethyl acetylenedicarboxylate N,N-Dimethylformamide : Flush vacuum pyrolysis Lithium diisopropylamide N-Bromosuccinimide N-Phenylmaleimide Tetracyanoethylene Tetracyanoquinodimethane N,N,N',N'-Tetramethy1ethylenediamine Nickel(II) acetylacctonate Bis(l,3-dipheny1phosphino)propanenickel(II) xi PART I THE SYNTHESIS AND REACTIONS OF AROMATIC COMPOUNDS c-FUSED with THIOPHENE INTRODUCTION w-Bxcessive heterocyclic compounds isoelectronic with naphthalene fall distinctly into two classes. The parent compounds in the so called "normal” series1 (1: x=o, benzofuran; X=S, benzo[b]thiophene; and X=NH, indole) are well known and quite stable. In contrast, the isoconjugate isomers (2 : X=I0 , isobenzofuran ; 2 X=S , benzo [ c ] thio- phene;3 and XaNB, isoindole4) are so reactive that they were not prepared until relatively recently. The extreme chemical reactivity of 2, the- o-quinoidal heterocycles, in contrast with the relative unreactivity of their stable Kekulé counterparts l is intriguing, since the two types of compounds differ only in the placement of the heteroa- tom. They both contain a bicyclic 101? electron array.5 3 Numerous studies concerned with the synthesis and reactivi- ty of the isoconjugate heterocycles have been reported. The current numbering system is as shown in 2. The quinoidal isomers are thermally unstable, air sensitive and react instantaneously with typical dieno- philes such as N-phenylmaleimide to yield Diels-Alder adducts. The dienophiles always add to the heterocyclic moiety instead of the carbocyclic ring, to regenerate the N 09° M ,X + on w HO benzenoid ring. The reactivity of 2 could be simply attributed to their polyenic or o-quinoidal character, but this seems to be inconsistent with the results of recent experimental and theoretical investigations which indicate the heteroatom lone pairs to be strongly coupled with the w -systems.6'7 Theoretical calculations performed. at. various levels of sophistication indicate that molecules of the type 2 are aromatic, but less so than the corresponding Kekulé compounds 1. In view of the historical connection between 4 aromaticity and diminished chemical reactivity, the poten- tial coexistence in this series of compounds of both aroma- ticity and high olefinic reactivity seems to present an apparent inconsistency. The most recent view of the electronic structure8 of this .series of compounds suggests that they contain a heterocyclic aromatic ring with a virtually noninteracting butadiene moiety. The aromaticity is said to arise primari- ly from the heterocyclic ring and does not extend over the entire ir system. The argument is based on the ratio9 of the vicinal coupling constants, J5,6 and J4'5, ‘which is believed to serve as an index of electron delocalization or localization. The ratio J5,6 / 04,5 in these compounds is nearly invariant at 0.72 i 0.02, which is close to the vicinal coupling ratio of the structurally similar 4. Structure 3 is claimed to be the best representation of the compounds. “3 / / ::: I45 \\ 6. 3 4 J3,4 = 0.758 J4,5 = 0.529 05,6 / 04,5 = 0.72 i 0.02 J4’5 / J3'4 = 0.70 This structural feature requires disruption of the system 5 in the heterocyclic ring and formation of a benzene ring during dienophile addition, leading to the observed hyper- reactivity. Structure 3 is able to explain the coexistence of aromaticity and high olefinic reactivity in 2. This model of 2 also provides a convenient rationalization for the reactivity in the series of o-quinoidal heterocycles. The activation energy for the Dials-Alder reaction can be con- sidered to involve two contributions: an endothermic contri- bution due to disruption of the 1r system in the five- membered heterocyclic ring, and an exothermic one due to the simultaneous formation of a benzene ring. The degree of cancellation determines the height of _. the activation barrier. The greater the resonance stabilization of the ”parent" five-membered heterocycle, the less reactive should be the bicyclic heterocycle. Thus, benzo[c]thio- phenelo is the most stable compound among them. The other argument, which considers the participation of the d orbitals of sulfur to form pd2 hybrid orbitals, suggests that the nonclassical form (6) contributes to the stabili- ty of benzo[c]thiophene (5). The d orbitals of sulfur participate to restore the aromaticity of the benzene ring in structure 6. 6 Isoindole 07) can tautomerizell to isoindolenine (8). The two forms can be distinguished by their 13 NMR spectra. The equilibrium position is markedly dependent upon the nature of the substituents and on the solvent polarity. Isoindolenine 8 is converted spontaneously and irreversible into 7, even at -40°C. The isoindole form 7 predominates in any solvent presumably because it has a resonance stabilization” energy greater than that of the isoindolenine 8, according to theoretical calcula- tions.11 In 1-arylisoindoles,12 the equilibrium position is shifted by the substituents on the aryl ring. This tendency is summarized in Table I. Electron-donating substituents in Table I. % Isoindole in the Isoindole ——-> Isoindolenine <— Equilibrium % isoindole in CDCl3 by NMR l-Phenylisoindole 91 l-(p-methoxyphenyl)isoindole 69 l-(p—dimethylaminophenyl)isoindole 50 7 the l-position shift the equilibrium toward the isoindo- lenine form. The l-position of isoindole was shown to be electron-rich by Dewar and Longuet-Higgins.13 Thus, electron-donating substituents in this position should destabilize the isoindole form. On the other hand, the 1-position of the isoindolenine form should be electron- deficient owing to the normal carbon-nitrogen double bond resonance. Thus, one would expect electron-donating substi- tuents to stabilize the isoindolenine form, as observed. The tautomeric ratio has been determined for l,3,4,7- tetramethylisoindole 9 in a variety of solvents14 by comparing the areas of the NMR signals at 56.4 and 7.0. The isoindolenine form 10 predominates, although the isoindole 064 670 11,12 The im- form has the greater resonance energy. portance of the isoindolenine form in this example is attri- buted to two effects: (i) electron-releasing groups favor the isoindolenine form and (ii) the isoindolenine ' form eliminates one of the peri-interactions present in the isoindole 9.15 8 The corresponding thiophene derivative l,3,4,7-tetra- methylbenzoEclthiophene 13, was synthesized from the O- . C: 6 HF / + s a S \ \ O 11 12 13 16 diketone 11 and 2,5-dimethylthiophene 12. The peri- -interactions in 13 were not mentioned in the literature. Peri-strain as a consequence of the Cl-C7 and C3-C4 methyls is expected to be important in 13. The first part of the thesis will describe the synthesis of a variety of methyl substituted benzo[c]thiophenes. In 1939, Schomaker and Paulingl7 suggested that an expansion of the sulfur octet could be a special factor in stabilizing the thiophene molecule. In resonance terminolo- gy, this concept can be represented by including structures with tetracovalent sulfur 14 as well as the related dipolar structure 15 in which the sulfur atom. bears a negative charge.17 8 ,‘S\ ‘ +< .87 14 15 Longuet-Higgins later' developed. this concept in {molecular 9 orbital terms, showing that the mixing of sulfur 3P2, 3dxz and 3de orbitals would provide three pd2 hybrid orbitals, two of which are nonorthogonal and capable of fl'- 18 In this way, sulfur heteroatoms can be treated overlap. as structural analogs of -C=C- units in conjugated systems. Critics of this model contend that there is no reason to suppose on the basis of stability alone that d-orbital participation is significant. Sulfur pd2 orbitals would be of too high energy and cause too much angle strain to participate effectively.19 Recent MO calculationsl’20 led to the general conclusion that sulfur d-orbital partici- pation is insignificant in the thiophene molecule. Fusion of thiophene to a benzene molecule gives rise to either of the forementioned heterocycles, benzo[b]thio- phene and benzoIclthiophene. Both of these compounds can be represented by the usual Kekulé structures. Thus, they are examples of classical condensed thiophenes. However, tetra- valent sulfur may be present in structures such as 16 and 17 where no uncharged singlet structure can be written /8\ X: S.O,N 16 17 Nw «\vs 10 other than one containing a tetravalent sulfur. Such systems represent novel structures in which the sulfur atom may' be considered. as being coaxed into using’ pd hybrid orbitals, even if this type of participation is negligible in thiophene and benzothiophenes. Naphtho[l,8-cd]thiopyran21 22 16 and its diphenyl derivative 18 have been synthesized and trapped by dienophiles as summarized in Scheme I. The substituted thieno[3,4-clthiophene with four phenyl groups 19 also has been synthesized and found to be isolable.23 The 24 initial synthesis involved acetic anhydride dehydration of 20 or reaction of 21 with P4510 in pyridine. Scheme I 11 Scheme I--cont'd ph Dh 9“ p P“ 0 Oh \ A020 \ \ P235 3 s / SO-——--> S / ,S 6—— / h h (Oh Oh Oh P“ O 20 ’ 19 2‘ However, the parent compound remains unknown.25 An attempt to prepare and trap the reactive molecule 17 (x = S) is decribed in this part of the thesis. Benzo[c]thiophene can be regarded as an ortho-xylylene (22)26 in which the two C-H bonds on the two'exocyclic carbons are replaced by C-S bonds. o-Xylylene is a member of a class of compounds called exocyclic benzenes, in which 22 2.3 2,4 25 the aromaticity of the benzene ring is interrupted by over- lapping the p-orbitals on the carbocyclic carbons with those of exocyclic carbons. Other exocyclic benzenes are 3 , 6 -dimethylene-l , 4-cyclohexadiene 23 , tetrakis (methyl- ene)cyclohexene 24 and hexaradialene 25. 'These hydro- carbons are very reactive. Hexaradialene is one member of ("I ‘3 (Y '1‘ ft {I £_l. 't 12 the class of compounds called radialenes, which are cyclic unsaturated hydrocarbons having n ring atoms and n exo- cyclic double bonds. Other examples are triradialene 26, tetraradialene 27 and pentaradialene 28. Hexaradi- alene27 is of considerable theoretical and synthetic \X [I I1 \[\ 26 27 23 interest because of its potentially stabilizing benzenoid topology as well as its possible use as a synthon for the construction of polycyclic nuclei. In contrast to the instability of the parent hexaradi- alene, hexaethylidenecyclohexane28 29 is found to be a stable compound. Stabilization of hexaradialene also can be achieved by incorporating sulfur-atoms into the cross—con- jugated system, as in benzo[l,2-c:3,4-c':5,6-c"] trithio- 29 Such a molecule may in another sense be phene 30. formally regarded as a derivative of the stable aromatic molecule triphenylene 31, in which the benzene rings have been replaced by c-fused thiophene rings. Other analogues of 31 with c-fused thiophene rings are 32 and 33.30 The synthesis of 32 and electrophilic substitution re- actions of 30, 32 and 33 are also included in this Part of the thesis. 13 31 32 33 Tetrakis(methylene)cyclohexene 24 can also be stabil- ized by the c-fused thiophene rings, as in benzoll,2-c:3,4- c'ldithiophene 34.31 In addition, structures 34 and 3532,33 can be regarded as analogues of phenanthrene 36 in which the benzene rings are replaced by thiophene rings. A new approach to the synthesis of 34 and a study [j 0 35 ’ 36 of its typical electrophilic substitution reactions are also covered in this part of the thesis. There has been current interest in the Dials-Alder reactions of thiophenes34. Because of its high aromatici- tY. it is well known that thiophene itself is inert to l4 maleic anhydride.34 However, aromatic ring fused thio- phenes such as 5 and 35 can undergo the Diels-Alder reaction easily. Thermally, 30 is the most stable among the exocyclic benzenes with c-fused thiophenes. The additional heterocyc- 1ic ring of 30 diminishes its reactivity and restores its overall aromaticity. Compound 5 naturally is the most reactive of this series of heterocycles. Benzodithiophene 34 decomposes upon overnight exposure to air. ‘The :final section of this part of the thesis will compare the reacti- vity of these thiophene derivatives towards a dienophile. RESULTS AND DISCUSSION A. SYNTHESIS OF THE DERIVATIVES OF BENZOIClTHIOPHENE 1. Synthesis of 4,5,6,7-Tetramethylbenzo[c]thiophene 57 In the literature, syntheses of the benzoIclthiophene skeleton fall into two categories. The first involves initial formation of a thiophene moiety followed by formation of the carbocyclic moiety. The synthesis of 35 benzo[c]thiophene-l-carboxylic acid 40 summarized in Scheme II is a typical example. Condensation of ethyl Scheme II 8 C023 C028 0 HSCH2002Et TSOH‘ A , EtON S ' \ S CHOEt a OEt 37 33 39 COZH 1. N BS ’1 A ._I ‘r—” S eb- ” S 2°h4€3CHNa “ - 4o 5 15 con la: III 16 mercaptoacetate with ethoxymethylenecyclohexanone 37 in the presence of sodium ethoxide yields 38 in one step. Dehydration of 38 with p-toluenesulfonic acid gives 39. Interaction of 39 with N-bromosuccinimide followed by treatment with sodium methoxide affords 40. The parent compound can be obtained in low yield through the decarboxy- lation of 40. The synthesis of 41, summarized in Scheme III,36 also falls into this category. Scheme III O / Br'2 Br I \S .9 ‘ S ' B O O Zn-Cu O 1. Base . / 4—f S 2. ESiCI “ ‘ o The other approach for making the benzoIclthiophene skeleton is to aromatize the thiophene ring in the last Step. For example, benzotclthiophene 5 initially was Prepared in low yield from the sulfide 43 by catalytic deb. 9.38 .16 564‘ (1' Al D l7 dehydrogenation at high temperature. Compound 43 can easily be obtained from 42 and ‘Nazs. Because benzo[c]- thiophene is thermally unstable, the high temperature used CI Na 8 N IE1:l ___2_—.>@ 3.3.10.8...» g—NTS CI 42 43 44 Pd/C 330°C 230°C / \ S 5 for dehydration could be responsible for the low yield. The elimination of toluenesulfonamide from 44, which can be obtained from the sulfide 43 by treatment. with. chlora- mine-T, by heating at 230°C gives benzo[c]thiophene,37 which was trapped by N-phenylmaleimide. Again the high temperature required for the elimination could be responsi- .b1e for the failure to isolate 5. Isoindoline N-oxide 45 has been shown to lose the elements of water when treated with acetic anhydride, to 5a This method has 38 affkard 2-substituted isoindoles 46. been extended to the preparation of benzo[c]thiophene. 18 O. A020 ’— .::“{R I 0 ~ NR NalO4 _. (80 A020 #migg'is 43 ' 47 tion Pumme the 48 wh neat: carri thio; ISAC‘ 19 Sodium periodate was found to allow the controlled oxida- 39 of sulfide 43 to the sulfoxide 47. The dehydra- tion tion of 47 with acetic anhydride may be viewed as a Pummerer reaction. Structures 48 and 49 are proposed as 32a The sulfoxide 47 is converted to the intermediates. 48 which then eliminates an acetate ion to give 49. The dehydration of 47 also can be achieved by using 38 The alumina dehydration method was neutral alumina. carried out in a sublimation apparatus, and the benzotcl- thiophene was collected on the cold finger. Although the reaction is a vacuum pyrolysis, the low temperature of the cold finger stabilizes the product, which can be obtained in 94% yield. Benzo[c]thiophene is a colorless low-melting solid with a strong naphthalene odor and is stable as a solid only under nitrogen for a few days at -30°C. The synthesis of stable isoindoles with methyl groups 40 The methyl on the carbocyclic system has been reported. substituted dichloride 50 was converted to the cyclized product 51 with methanesulfonamide. The elimination of methanesulfinic acid with sodium hydride gives a mixture of 52 and 53, which are tautomers. The methyl groups have a significant influence upon the stability of the tauto- meric forms. Structure 53 seems to be favored by methyl substituents at the 4,7-positions adjacent to the fused pyrrole ring. Methyl groups at the 5,6-positions probably contribute inductively to the stabilization of the struc- ture 52, which contains a benzenoid moiety. The three 20 methyl substituted compounds (53a, 53b and 53c) are more stable than the parent compound in both tautomeric forms. ”“2025Me Rn @ N—SOzMe 51 A NaH (1 F17 I ':15 R 450 z’ a’ \ - \ 53 a. R4 8 R7 = Me b. RS 8 R6 = Me c. R4 = R = R6 = R7 = Me It was believed, judging from the relative stabilities of methyl substituted isoindoles and isoindole itself, that 4,5,6,7-tetramethylbenzo[clthiophene 57 would. be more stable than the parent compound. Dehydration of the corres- ponding sulfoxide with neutral alumina seems to be the most efficient of all the methods used to synthesize the benzo[c]thiophene skeleton. C1 54 55 56 Al203 ON ON - on e:s ‘CN _ . ' 57 Dichloride 54 was easily obtained by the chloro— methylation of prehnitene. Cyclization of 54 with NaZS‘9HZO was carried out in very dilute aqueous ethanol solution. The cyclic sulfide 55 could be easily separated by recrystallization from cyclohexane and ethyl acetate. Oxidation of sulfide 55 to the cyclic sulfoxide 56 was achieved in two ways, with sodium periodate or 41 The sodium periodate oxi- with N-bromosuccinimide. dations need longer reaction times. The NBS reaction se- quence is summarized in Scheme IV. The reaction was worked Scheme IV N 88 S aq. acetone 755 .e-~._- A. 22 up after the mixture of cyclic sulfide 55 and NBS had been stirred for half an hour. The sulfoxide 56 was re- crystallized from benzene and hexane. Alumina dehydration of 56 was carried out in a subli- mation apparatus. A mixture of alumina and sulfoxide 56 was heated under 25 mm Hg pressure at 150 - 160°C to give the product 57, which was collected on a cold finger. The tetramethyl derivative of 5 is more stable than the parent compound as expected. It can be kept at room temperature for several hours without decomposition, but the colorless solid turns yellow within a day in the air. The solid can be kept at 0°C for months without any color change. Even so, 57 still undergoes cycloaddition with TCNE to restore the endocyclic aromaticity of the benzene ring. 2. Synthesis of l,3-Dimethylbenzo[clthiophene 60 The 1,3-dimethyl substituted derivative of benzo[c]- thiophene was synthesized by the same dehydration method. In order to prepare the precursor, the sulfoxide 59 was prepared by stepwise deprotonation of 47 with base follow- ed by quenching with methyl iodide. Treatment of sulfoxide 47 with one molar equivalent of LDA formed the monoanion which was trapped by methyl iodide to give monomethyl— sulfoxide 58. The same reaction was repeated on 58 to 23 give 59. Compound 59 was dehydrated with alumina to give 60. ‘ 1.1eq.LDA 1,1 , $0 + 3 eq LDA. 2. Mel (>0 2. Mel SO 47 58 59 A|203 , S \ 61 60 Although l , 3-dimethylbenzo [ c 1 thiophene 60 can be isolated at room temperature, it is not stable. It was characterized by its adduct 61 with TCNE. The TCNE adducts of all benzo[c]thiophene derivatives undergo a retro Diels-Alder reaction shown in their mass spectra. The high reactivity of 5 must be due to the low value of the delocalization energy and the very high value of the free valence at the l and 3 positions. The highly unstable isoanellated aromatic ring system can be stabiliz- 2 ed by incorporating phenyls4 at the l- and 3-positions as in 62a, or an electronegative substituent43 at any position of the skeleton, as in 62b. The inductive effect cannot explain the relative stability of the tetramethyl derivative 57 , because the electron-donating methyl 24 Ph I w 11 62a Rl - 62b R CO Me 62 groups should destabilize the skeleton. The thermal stabili- ty of 57 must be due to steric effects which slow down bimolecular reactions of 57. The inductive effect of the methyl groups in 60 may be responsible for its instabili- ty. 3. An Approach to the Synthesis of Hexamethylbenzolc]thio- phene 65 The successful synthesis of l,3-dimethylbenzo[c]thio- phene 60 from 59 encouraged us to apply the same strate- gy to the synthesis of 65, as shown in Scheme V. The sulfoxide 56 was treated with one molar equivalent of LDA to give a monoanion intermediate which was quenched by excess methyl iodide to give the pentamethylsulfoxide 63. In the mass spectrum of the crude product, the parent peak due to hexamethylsulfoxide 64 was also observed. The treatment of 56 directly with two molar equivalents of LDA at -20°C and excess methyl iodide did not give the desired precursor 64. If the base-treated solution was quenched with methanol instead of methyl iodide, 4,5,6,7- tetramethylbenzo[clthiophene 57 was isolated. That is, 25 the sulfoxide oxygen and two hydrogens were lost. Scheme V 1.1e .LDA . . I 30 q ,. SO 1.199.595» so 56 . 6.3 I 1.2eq.LDA I AI 0 2.MeOH l 2 3 1 ’ \ / 57 S \ 65 4. A Mechanistic Study of the Dehydration of Cyclic Sulfoxides with Base 44,45 In the literaure, there are only two reports concerned with the synthesis of benzo[c]thiophene and benzo[clselenophene 66 with base. Benzo[clselenophene was prepared either from the dibromide 68 or from the selenoxide 67 by treatment with 40% sodium hydroxide solution for two hours. The yield was 32%. Benzo[c]thio- phene was also prepared by this method, but in only a 4% yield. Two intermediates 69 and 70, were proposed but without evidence. H202 I ’ Se —-> SeO——' 5 7 OH- 26 HBr 27 Because the tetramethylbenzolclthiophene 57 is more stable than the parent Compound and can be isolated at room temperature, it seemed more likely that intermediates analogous to 69 and 70 could be identified during its synthesis. After treatment of the sulfoxide 56 with two molar equivalents of LDA at ~20°C, excess MeOD was added. The product was the mono-deuterium substituted tetramethyl- benzo[c]thiophene 71. When methyl iodide was added in- stead of MeOD, pentamethylbenzo[c]thiophene (72) was isolated. Its structure was characterized through its TONE adduct. . 9 SO- 1.2eq.LDA+ ’ S 2. MeOD \ 71 56 1.2eq.LDA Oz TCNE —> . S 2. Mel ‘ 28 The isolation of 71 and 72 can be rationalized by the 29 mechanism. shown on page 28, involving' two intermediates analogous to those proposed. The first Species 69a. <-—> 69b is formed after addition of two molar equivalents of LDA. It seems likely that the predominant contributor to the resonance hybrid is 69b in which one of the negative charges is predominantly on the electronegative oxygen atom. The dianion is converted to the quenched intermedi- ates (70a, 70b) by MeOD or Mel, and these in turn aroma- tize to the corresponding products (71, 72). The re- action was found to occur even at -100°C. This is a novel example of the preparation of thiophene derivatives at low temperature. A similar mechanism was also suggested in 1968 for the 6 dehydration of the fused six-membered4 ring sulfoxide 18 with phenyllithium. However, there was not enough o 8 p 5 0h Ph 9 e 9h @ PhLi 4» 18 30 evidence to support this pathway at that time. The NMR spectrum of 71 indicated a substantial iso- tope effect in the final step. The kH/kD ‘value, calcu- lated from the mass spectrum, was approximately 4.0. The product distribution is controlled by the the aromatization step. When 57 was treated with two molar equivalents of LDA followed by quenching with MeOD, deuterium: was not incorporated into the a-position of the thiophene ring. The result indicated 57 could not be formed without the inter- mediates (69 and 70). The need to form the dianion was D C ’ 1.2eq. LDA C, S —# a S ‘ 2. MeOD ‘ » * 71 57 further established by treatment of 56 with only one molar equivalent of LDA, and then excess methyl iodide or MeOH. Only compound 63 or starting material were isolated, instead of the aromatized product. Mel 56 63 MeOH 31 Elimination reactions with base have played an impor- tant role in the synthesis of isoindole and isobenzofuran derivatives.47'48 For instance, 1,4—elimination and 1,2- elimination with base as shown in Scheme VI are capable of disrupting the aromaticity of the benzene ring' to form benzo[clfuran and isoindole. The dehydration described here of the sulfoxide to prepare a benzo[c]thiophene with-LDA at Scheme VI OMe ~ H O 14-elimitn. .— I” (3 @ LDA C\ H H AKDCD h , - ' 1 © “213 12 ellmln. N base / L5 H shut low temperature is an unique reaction. It is different from the direct 1,2- and 1,4-eliminations used in the preparation of isoindole and benzo[clfuran derivatives, since it proceeds via a dianion. 32 5. Synthesis of Hexamethylbenzo[c1thiophene 65 The fully methyl substituted benzo[c]thiophene 65 remained as a target compound. Although Scheme V (p. 25) presents one possible approach, an alternate approach was to use the already prepared. pentamethylbenzoIc]thiophene 72 as the precursor of 65. The a-position of thiophenes usually is somewhat acidic, and it is possible to deproton- ate the deposition of a thiophene ring with a strong base. Pentamethylbenzo[c]thiophene, prepared in the mechanis- tic study, was dissolved in anhydrous THF. The mixture was treated with 2 molar equivalents of n-BuLi at -20°C to form a monoanion which was then trapped with excess methyl iodide. After workup, the NMR spectrum of the crude product consisted of three singlets at (52.76, 2.48 and 2.05. This spectrum indicated that 65 was formed. However, during attempted purification the compound dimerized. The NMR dimer 33 spectrum of the dimer showed the presence of a vinyl proton (66.47, 3), two tertiary protons adjacent to methyl groups (64.76, <1, J=6.9 Hz: 4.42, q, J=6.9 Hz), and eleven methyl groups. The dimer was not identified. Evidence that the target compound had formed was ob- tained by preparing its TCNE adduct 73. After 65 was prepared, TCNE was immediately added to trap it. The NMR spectrum of 73 consisted of three singlets at 62.44, 2.42 and 2.24 which are due to the methyl groups. Two factors probably destabilize 65 with respect to dimerization. These are: (i) the inductive effect of the methyl groups at the l- and 3-positions destabilizes or enhances the reactivity of the skeleton and (ii) the peri- interactions raise the energy of 65. B. APPLICATIONS OF LDA AND MeOH TO THE AROMATIZATION OF CYCLIC SULFOXIDES 1. Synthesis of 5,6-DimethylbenzoIclthiophene 74 and Benzo[c]thiophene 5 with LDA and Methanol Since dehydration of the aromatic ring fused sulfoxide ‘ 56 with LDA under argon atmosphere at -20°C gave a better yield of the aromatized product 57 than with neutral alumina, the method was extended to the synthesis of other symmetrically substituted benzo[c]thiophenes. Besides 57, 5 and 74 can be prepared by this method. 34 The sulfoxides were prepared as before and treated with two F1 R o ._y... o 16:0 R I R “$3 R mm 7.4a 1.2eq.LDA 2MeOH R N 'CN- TONE ’S a , Iv“— CN md S’RzH 74 R:Me molar equivalents of LDA at -20°C. The mixture was quench- ed with methanol at -20°C. After careful removal of the solvent, each compound could be isolated. Because they were unstable, however, TCNE4£5 was added to a benzene solution of the compounds (5, 74) to determine the yields. The yields were about 80%. The reaction conditions are very mild so that the products do not decompose. The dehydration of sulfoxide 59 under the same condi- tions was incomplete, and gave some starting material in addition to 60. The main reason is the inductive effect of the methyl groups which suppress the formation of the required dianion 75. 35 ‘1. . I @ so no LDA ' C s +S,M. 2.MeOH ‘ S 2. Synthesis of Naphtho[l,2-c1thiophene 35 and Naphtho[2,3-clthiophene 76. The dehydration of sulfoxide 76 with alumina to give 35, which is much more stable than 5, has been report- .32 The stability of 3531a is probably due to the ed aromaticity of the benzene ring. Treatment of 76 with two equivalents of LDA and methanol gave 35 in a better yield (87%) than was obtained with alumina (43%). Naphtho[2,3-cl- thiophene 78, an isomer of 35, has an extended conjugat- ed system and is very reactive due to the loss of aromatici- 32 ty in the naphthalene ring. The sublimate from the de- hydration of sulfoxide 77 with alumina did not give any 36 so / 3 / es »O‘V 43% 35 76 1. 2eq.LDA 2 MeOH 87% aromatized product 78.31a A recent report showed that 78 could be prepared by flash vacuum pyrolysis;49 it was trapped with N-phenylmaleimide in 7% yield. Dehydra- tion of 77 with LDA, followed by cycloaddition to TCNE AIO ’ oo .. «as 18 77 7 A .leN FVP 1 00 “'P“ H gave 28% of the TCNE adduct 79: TCNE added to the hetero- cyclic moiety. The isomeric TCNE adduct 79a, in which the m. m... 7 n‘d 37 _ dienophile would have added to the central moiety, was not found . 1.Zeq.L,D_A> C " 8 @ SO 2. MeOH \ 77 78 TCNE 3. Synthesis of 4,5,6,7,8,9-Hexamethylnaphtho[2,3-c1thio- phene 83. Compound 78 has resisted isolation. It was thought that methyl groups might stabilize 78 as they do the parent compound benzo[c]thiophene. The synthesis of hexa- nethylnaphtho[2,3-c]thiophene 83 is summarized in Scheme VII. The same steps are used as in the of synthesis of 57. Treatment of 86 with LDA followed by quenching with methanol gave an orange solution. Attempts to isolate 83 38 Scheme VII 00 :-—~——-oe 80 81 N88 were thwarted by its decomposition on TLC plates. TCNE was added to the orange solution to trap 83. Two adducts, 84 and 85, were isolated in an eight to one ratio. The adduct 84, in which TCNE added to the thiophene ring as usual, was the major product. The other product arose from TCNE addition to the central six-membered ring. Addition to the central ring releases peri-strain of methyl groups. 39 4. Synthesis of Phenanthro[9,10-c1thiophene 33. 30 The initial literature synthesis of 33 is sum- marized below. The diketone 86 underwent nucleophilic (NOhH 502 I S “002 » l \ D \ C02H 33 Al203 O SC) addition of diethyl thioglycolate in the presence of sodium methoxide, followed by dehydration to give the acid 86a, which was decarboxylated to' 33. Alumina dehydration50 of the sulfoxide 87 also gave 33. In order to synthesize 33 with LDA and methanol, sulfoxide 87 was required. The dibromide 88 could not be cyclized with Nazs.9HZO because of the low solubility of 88 in aqueous ethanol solution. Instead thioacetamide and potassium hydroxide in 51 benzene-ethanol solution was- used to cyclize the dibromide 88 in very dilute solution. Dehydration of 87 S 40 5 Br KOH O 88 880 NBS H20 . ’ 54.2mm» so i \ 2.MeOH O 33 87 with two molar equivalents of LDA and methanol gave 33 in 51% yield, which was better than was obtained with alumina. 5. An Attempt to trap Thieno[3,4-c]thiophene 17. Two thiophene rings can be fused together in four dif- ferent ways, giving rise to the four isomeric thienothio- phenes 89-91 and 17. Isomers 89-91 have classical structures and are known to be isolable compounds.52 Isomer 17, thieno[3,4-clthiophene, has a nonclassical structure. The symmetry of 17, which allows both sul- furs to have partial tetracovalent character, would appear 41 89 9O / / ~S S \ \S S / / 91 17 to make 17 a particularly favorable molecule for sulfur d-orbital participation in the bonding. In the absence of such participation, the molecule must either have the character of a thiocarbonyl ylide 92a or a diradical 92b. \ I / \ ' \ / \ I / \ e e . . 17 9.2a 92b 53 The first. derivative of 17 was reported in 1967. Attempts to dehydrate sulfoxide 93 with acetic anhydride ~ to give l,3-dimethylthieno[3,4-c]thiophene 94 led to no isolable product. However, dehydration of 93 with acetic anhydride in the presence of N-phenylmaleimide showed that 94 was produced as a transient intermediate, since both the endo and exo adducts 95 were isolated in reasonable yield. 42 s s s \ / A020 \ / NPMI \ / \ / S o S H O N Ph 93 h .94 -95 The parent compound 17 remains unknown, although the 5 4 The corres- related sulfide 96a has been synthesized. ponding sulfoxide 96b was prepared by the treatment of 96a with sodium periodate. Use of NBS in aqueous acetone solution to oxidize 96a resulted in a low yield of 96b, because the a-position of the thiophene derivative 96a s s S X X X . Ln-B L \ / N328 \ / U' ’ \ / _ 2.MeOH S S X X - 96a X=Br Na|O4 v S 1.2qu.DA \ / potymert 2.MeOH DMAD s 0 96b 43 was labile toward NBS. The sulfoxide 96b was treated with two molar equivalents of LDA at -70°C in the presence of dimethyl acetylenedicarboxylate. Quench with MeOH resulted in a polymeric solid. No adduct of 17 and dimethyl acety- lenedicarboxylate was found. Dehydration of the dibromosulfoxide 98, which was ob- tained from the oxidation of 9755 with NBS, with two molar equivalents of LDA at -70°C or -20°C in the pre- sence of DMAD afforded the deSulfurized product 101 in 1% or 2% yield. The isolation of 101 could be a consequence of forming the nonclassical thiophene 99 after the solu- tion was quenched with MeOH. Nonclassical thiophene 99, s x x s X s H NBS H 1.2eq.LDA \ / )- ##- 2.MeOH 3 +120 8 / 97 99 9s DMAD N%§ BrsBr XSX XSX \/ -S \/ " Q“ 6 x E E =Br E E 9 97a IOI- 100 44 formed in solution, undergoes cycloaddition with dimethyl acetylenedicarboxylate to give the intermediate 100. This species is then desulfurized to give 101. In the literature, the tetraphenyl derivative of thieno[3,4-clthiophene 104 underwent cycloaddition with dimethyl acetylenedicarboxylate in refluxing xylene. The 104 105 106 24 but lost element- initial adduct 105 was not isolable, al sulfur to give the fully aromatic benzo[c]thiophene skeleton 106. In compound 99, the two thiophene rings are not iden- tical. The electron-rich thiophene ring should be more reac- tive toward dienophiles. For example, in structure 94, -the ring with methyl groups is the electron-rich ring. Thus N-phenylmaleimide adds to this substituted moiety to form 95.56 In structure 95, the sulfur atom. is not elimi- nated because the elimination would not result in aromati- zation. On the other hand in 109, the ring with the carboxylate groups is the electron-deficient part of the 4S molecule. Therefore, the dienophile adds to the unsubstitut- ed ring to form 11056. s s \ / A020 a \ / NPMI 3 E=002Me 109' The proton NMR spectrum of 101 consisted of two singlets at 57.90 and 3.94 in a one to three ratio. Six peaks at 6167.76, 135.94, 126.51, 122.83, 107.72 and 53.44 appear in the 13C NMR spectrum. Based on these data, the isomeric structure 101a cannot be totally ruled out. av 46 6. Synthesis of 3,4-Diphenylthiophene 112 from the Sulf- oxide 111 It was hoped that this method could be extended to the synthesis of ordinary thiophene derivatives in addition to aromatic ring condensed thiophene derivatives. Sulfoxide 111, prepared according. to the literature,57 was treat- ed with two molar equivalents of LDA at -20°C. After work- up, a brown oil was obtained. The oil could not be purified on TLC. The oil mixture, when submitted to GC-mass spectral analysis, gave a molecular ion corresponding to 112. The 8 s . 0 S E\ /( LA _ 1.2eq.LDA \ / y. a 111 112 GC—mass spectrum indicated that 11258 was formed in low yield. In conclusion the use of excess LDA with sulfoxides provides a a potential route to aromatic ring fused thio- phenes. Although the method was also applicable to the aromatization of 111, a typical example of an ordinary thiophene, the low yield discouraged further work. 47 C . SYNTHESIS AND CHEMISTRY OF BEN ZOI l , 2-c: 3 , 4-c ' IDITHIO- PHENE 34 AND ITS BROMINATION COMPARED WITH THAT OF NAPHTHOI 1 , 2-C1THIOPHENE 35 l. A New Approach to the Synthesis of Benzo[l,2-c:3,4-c'1- dithiophene 34. The fusion of two thiophenes to adjacent positions of a benzene ring gives rise to six possible isomeric benzodi- thiophenes as shown below, 113-117 and 34. Of these possible isomers, compound 34 shows less formal resem- blance to phenanthrene than do any of the remaining com- pounds. Several resonance forms (34a, 34b) of 34 may I s S / S \\1 \\ 1 \ \ \s -6_ _H4 115 116 117 35,1 '8 8 4* <—* —> 4/ 7 /12 58'6 § 34 34a , 34b 48 be written in which the central ring possesses a benzenoid structure. Structure 34 would be a more critical reso- nance form than structures 34a and 34b, so the possibi- lity of electron delocalization across the 9-10 and 11-12 bonds is decreased in structure 34. In fact, benzo[l,2-c:3,4-c'Jdithiophene 34 has been 59 synthesi zed previous ly from 118 and 119 . The syntheses are summarized in Scheme VIII. They fall into the Scheme VII 5 \ \ HO ,_ H N2H4 / O I 118 s 5 . \ \ 000 + / 0 I 34 1.n—BuLi 49 first category of polycyclic thiophene derivative synthe- sis. The UV spectrum of 34 indicates that the double bond in 34 is more like. the double bond in cis-stilbene than it is like the 9-10 bond in phenanthrene. The dehydrogena- tion of 120 with DDQ to 34 has also been reported.29 This method, which improves the yield of 34, belongs to the second category of thiophene synthesis. . An alternative approach to the synthesis of 34 was sought in order to improve the yield. The dehydration of monosulfoxides with neutral alumina has been successfully applied to various thiophene derivative syntheses. Neutral alumina probably would dehydrate a disulfoxide such as 121. Compound 121 was prepared. by the oxidation of the disulfide 120 with sodium: periodate. The sulfoxide 121, mixed with neutral alumina. in. a. one to one ratio, was dehydrated in a sublimation apparatus at 25 Torr and 140- 150°C. The product was collected. on the cold finger in 63% yield. 50 An attempt to dehydrate 121 with four molar equiva- lents of LDA led to an inseparable mixture. No 34 was found among the products. The failure of this method is probably due to difficulty in forming the required inter- mediates. In the intermediate 122, the benzene ring would 122 have to bear too many negative centers. 2. Bromination, A Typical Electrophilic Substitution Reaction of 34 Bromination has been regarded as a typical electrophi- lic substitution reaction of heterocycles. For example, the bromination of 113 and 115 is summarized Scheme IX. The 51 Scheme Ix 5 \ Br \ 6. / Br2 331‘2 —-——> 5 / 113 Br 8 Eng a». / s 115 Brz 52 electrOphilic substitution does not occur at the benzenoid moiety. Compound 115 is brominated more selectively59b than compound 113. The a-positions of the thiophene ring in 115 are more reactive than the B-positions. So far there has been no report concerning the electrophilic subs- titution reactions of 34. Initially, bromine in CCl4 was used to brominate 34. The addition of bromine in CCl4 to 34 gave a purple solution. Workup resulted in decomposition of the product. NBS in acetic acid. solution has been used for 60 The bromination of brominating thiophene derivatives. 34 was performed by this modified condition. One molar equivalent of NBS was added to a solution of 34 in acetic acid at room temperature. Three products (123, 124 and 125) Jig—p decomposed product 6‘ Br 6‘ / / / / 34 1eq.NBs B+r AcOH \ \ \ s ‘ s 123 125 Br were isolated by column chromatography. Compounds 123 and 124 are the isomeric monobromination products. The NMR spectra of 123 and 124 are summarized in Fig I. i Fig I 123 7.7l(d, J-O.GHz) 7.04(dd, Jl=1OBz, J2=O.GHz) 7.18(dd, Jlaloaz, J =0.9Hz) 7.75(dd, J 23.132, 32:0.932) 7.50(d, J= .le) (dd) \ \ 7.48(d) 8.55(%d) 125- 6.95(d, J=IOHz) 7.l3(dd, Jl=lOHz, J =0.9Hz) 8.55(dd, J =3.0Hz, 32=o.9az) 7.48(d, J= .OBz) Br 6‘ 5,99 / 239(3) (d) 7.08 (dd) \ \ 746(d) S 8. 59(dd) 124 6.99(d, J =9.SBz) 7.08(dd, 5 =9.SHz, J =0.9Hz) 8.59(dd, J =2.BBz, J2=0.9Hz) 7.46(d, J: .832) 7.39(s) 1253 54 The cis vinyl protons in 123 couple each other with a coupling constant of 10 Hz. This two protons are also respectively coupled by the adjacent protons on the thio- phene rings so that they appeared as two double doublets. In 124, the vinyl proton close to the bromine atom appears as a doublet. The other vinyl proton appears as a double doublet because there is an adjacent thiophene pro- ton. The proton on the brominated thiophene ring in 124 shows as a singlet. In 123 and 124, the protons of thiophene rings couple each other with coupling constants of 3.1 Hz and 2.8 Hz. The 13 CMR spectrum of the dibromide shows ten aro- matic carbons, so there are two possible structures, 125 and 125a, for this compound. In 125a, the proton on the 3-position should be a singlet as in 124. Structure 125a is ruled out because there is no singlet appeared on the 1HMR spectrum. The proton assignments of 125 is also shown in Fig I. When 34 was brominated with three molar equivalents of NBS, isomer 126 was isolated as the only product. Com- pound 127 was isolated when 34 was treated with four molar equivalents of NBS or when 126 was further treated with NBS. The bromination did not go further when 34 was treated with excess of NBS. In the course of bromination, the typical electrophilic substitution never occurs at the vinyl positions, in sharp contrast with the bromination of phenanthrene. Thiophene is known to be more reactive than 55 Br \w \ \ Br 5 Br was Br 8 / / Br 127 benzene toward electrophiles, particularly at the -posi- tion in a condensed system, but compound 34 provides asystem to study the competition for electrophilic substi- tution between thiophene and the double bond-like moiety. 3. Synthesis of 7,8-Dibromobenzotl,2-c:3,4-c'Jdithiophene 130 and its bromination For the synthesis of hexabromide 131, compound 130 was made from 129 with DDQ as the dehydrogenation re- agent. The disulfide 129 was prepared from 128 and NaZS.9HZO by the known route.62 The 1H NMR spectrum of 130 consists of two doublets at 67.85 and 7.75 (J=3.2 Hz). 56 Br DDQ Br I / Na S ©0HBH4 2 "' ' 2 Br \ 3, \ 128 130 Br / ‘8 Br / Br Br \\ Br ‘8 132b Four molar equivalents of N88 in acetic acid was added to a solution of 130 in acetic acid and the solution was 57 stirred overnight to complete the reaction. A single penta- bromobenzodithiophene 132 was isolated. There are two possible isomeric structures for this pentabromobenzodithio- phene, 132a and 132b. The 1H NMR spectrum of 132 consisted of only one singlet at 68.72. The mass spectrum indicated a pentabromo derivative. Neither structure 132a nor 132b can be ruled out, although 132a seems the more likely, since 132b is sterically crowded. Indeed steric hinderance is probably the cause of resistance to further bromination. 4. Metalation of 34 with two molar equivalents of n-BuLi Metalation of 34 with one molar equivalent of n-BuLi and trapping with OMB have been reported.31 Monometala- tion occurred mainly on the a-positions of the thiophene moiety, and the product was trapped by DMF to give 138a and l38b. Dimetalation of 34 could result in four iso- meric dianions. By use of DMF as a trapping reagent, four isomeric dialdehydes 133, 134, ~135, and 136 could be isolated. Among the dialdehydes, compound 133 might be further used to the synthesize 137, another novel benzo- [c]thiophene. Two molar equivalents of n-BuLi were added to a solu- tion of 34 in TMEDA and then excess DMF was added to the solution. Only one of the isomers could be isolated pure, in 29% yield. The 1H NMR spectrum of this compound 58 1. 260. n-BuLj L2. ow: S // HO \ \ OHC 1'33 134 135 136 Y .9 // \ ‘ S 137 consisted of three singlets, at 610.17, 8.34 and 8.14. Structures 133 and 135 are the two possibles isomers 59 which should show three NMR singlets. In 3-formylbenzodi- 31 the vinyl protons appear as a singlet thiophene 138a, at 57.27. In structure 138b, the vinyl proton close to the formyl group shifts downfield (to 67.88) because of the proximate anisotropic effect of the formyl group at the l-position. Based on this NMR spectral analysis, the pro- duct isolated should be 135, in which the benzenoid pro- tons are shifted downfield by the adjacent formyl groups. 7.88 8' 72 1'35 . ‘ 138a 138D S. Bromination of Naphtho[l,2-clthiophene 35 The electrophilic substitution reactions of naphtho- [1,2-b]thiophene 139a and naphtho[2,1-b]thiophene l39b have been reported.“ However, the corresponding re- actions of naphtho[2,1-c]thiophene, another analogue of phenanthrene with a c-fused thiophene ring, have not been reported. Two molar equivalents of bromine in CHCl3 solution were added to 35 in CHCl3 solution. The dibromide 140 was obtained in 41% yield. The 1.H NMR spectrum of 140 60 1393 . 139b Br2 is summarized in Figure II. Under such reaction conditions, the bromine did not attack the vinyl positions. When compound 35 was brominated with two molar equi— valents of NBS in acetic acid, in addition to 140, two other compounds 141 and 142 were also isolated. When dibromide 140 was treated with NBS in acetic acid, 141 and 142 were again isolated. Compound 142 also hydrolyz- ed slowly to 141 in the air. The proton spectra of 141 and 142 are summarized in Figure II. The possible isomeric structure 142a. was ruled out for 142 by use of chemical shift reagent. The vinyl proton close to the carbonyl moiety in structure 142 was most strongly shifted downfield. The result is shown in Fig. III. 61 7‘ 323 7.95 194 (d) 8.10 809(d.J=8Hz) (d.J=8.5HZ) 14o __ _ 141 142 The formation of 141 from 140 can be rationalized as Scheme x Br / 141a 141 ‘42 62 who: Io. . «a... .I I. '.‘. “9. x D Is Im 24... 5 0.» Br 0006 Nm 0 MCAfiOUvQ 0.. 0.» Ob .. 03 O.m 0.0 O.V Ob Bot“: 3:0 o. mimocvulan 63 in Scheme X. The abnormal bromination is probably favored by restoration of the naphthalene aromaticity. As further proof of the sturcture for thioanhydride 141, it was hydrolyzed to the known diacid 141a by aqueous hydro- chloric acid. D. SYNTHESIS OF NAPHTHO11,2-c:3,4-c'1DITHIOPHENE 32 AND ITS BROMINATION COMPARED WITH THAT OF BENZOTRITHIOPHENE 30 AND PHENANTHROTHIOPHENE 33 1. Synthesis of Naphtho[l,2-c:3,4-c'1dithiophene 32 In order to compare the brominations of 30, 32 and 33, naphtho[l,2-c:3,4-c']dithiophene 32 was prepared by the same strategy29 used to synthesize 30, as follows. Treatment of 1,2,3,4-tetramethylnaphthalene 145 with four . B 145 146 147 64 molar equivalents of NBS in the presence of a trace of benzoyl peroxide in refluxing CCl4 solution gave 146 which was cyclized by NaZS.9H20 to give 147. Sulfide 147 was dehydrogenated with DDQ in refluxing chloro- benzene to yield 32 as colorless solid. The 1.H NMR spec- trum of the benzene ring protons of 32 shows two double doublets at 68.80 and 7.43 (J1 = 6.2 Hz, J 2 Hz). 2 In addition, two doublets appear at 67.91 and 7.70 (J = 3.0 Hz) due to the protons of the thiophene rings. One of the double doublets, appearing downfield at 68.80 is due to the protons at the peri positions of the naphthalene ring. The downfield shift is due to deshielding by the adjacent thiophene rings. The protons on the thiophene ring are downfield compared to the C-2 proton in thiophene ( 67.19). This downfield shift is also caused by the ad- jacent benzene and thiophene rings. 2. Bromination of 30, 32 and 33 a) Bromination of 33 Although compound 33 has been synthesized,50 there has been no report about its bromination. It is assumed that the electrophile will attack the a-position of the thiophene ring. When compound 33 was treated with 'two molar equiva- lents of NBS in acetic acid, dibromide 148 was isolated as the major product. The bromine attacked the a-position 65 of the thiophene ring as expected. It was reported50 that one molar equivalent of NBS in aqueous acetone solution at 50°C oxidized 33 to 87. Change of the reaction solvent from acetone to acetic acid led to electrophilic substitution instead of oxidation. When dibromide 148 was I 8 1eq. NBS \ acetone treated with excess NBS in acetic acid, as with 140, it gave rise to 149 and 150 in which the aromaticity of the phenanthrene ring was restored. 66 b) Bromination of 32 Canpound 32 was brominated with four molar equiva- lents of NBS. Tribromide 151 was isolated after the re- action mixture was stirred overnight..The proton NMR spec- trum of 151 consists of three multiplets at 69.22 (1H), 9.17 (1H) and 7.50 (28), and a 8189181: at 68.71 (18). Because there are three downfield shifted protons which should be close to the bromine atoms, the alternate struc- ture 151a in which there is only one proton close to bromine atom was ruled out. The protons close to bromine atoms in 148 and 153 are also shifted downfield. The NMR spectra of 148 and 153 are as summarized. 67 148 153 Treatment of 151 with NBS in acetic acid did not give the tetrabromide 152. Bromines are able to replace the two thiophene n-protons in 33. However, the bromi- nation ceases at the tribromide stage in 32. The steric hinderance in structure 151 does not allow the fourth bromine atom to be introduced. c) Bromination of 30 62 with exdess Compound 30 has been brominated bromine. Only tribromide isomers were isOlated. It was thought that NBS in acetic acid solution might be able to brominate the other positions of 30. Benzotrithiophene 30 was treated with four molar equivalents of NBS in aceticiacid. After the reaction mix- ture was stirred overnight, only tribromo isomers were isolated. Based on NMR spectral analysis, the tribromo isomers are 154 and 155 are formed in a three to one 68 Scheme XI 154 155 69 ratio, which agrees well with the statistical ratio for the formation of 154 and 155, as shown in Scheme XI. Iso- mers 154 and 155 also contain no sterically interfering bromines in the same “wedge” of the structure. E. COMPARISON OF THE CHEMICAL REACTIVITY OF 5, 30 AND 34 The c-fused thiophene moiety in condensed systems undergoes cycloaddition reactions with dienophiles. For example, 116 and 117 have been reported to serve as dienes.“ The b-fused thiophene moieties do not have this property. E E E E S I / S DMAD O O 3 / 3 / 6‘ / 116 E «E ‘8 0 j- S 70 Benzo[c]thiophene 5 is known to react with TCNE to 45 form a cycloadduct. Although 30 has three c-fused thiophenes, it does not undergo [2+4] addition with TCNE or any other dienophiles. A C-T complex29 is formed from 30 and TCNE. Compound 30 serves as an electron donor in the complex. Benzodithiophene 34, with two c-fused thiophene rings, can be considered as intermediate between S and TCNE fast TCNE ' n- C -T complex NPMI I—-—->N.Fl. TCNQ >C-T complex TCN E _——>C-T complex 71 30. It may undergo cycloadditions with dienophiles, as do 116 and 117. Various dienophiles were tried to initiate a Diels-Alder reaction with 34. N-phenylmaleimide did not undergo the cycloaddition with 34. In fact, 34 formed C-T complexes with TCNQand TCNE (2 equivalents). The com- plexes were dark blue solids. The C-T complex of 34 and TCNE was redissolved in a mixed solvent of chloroform and acetone. While the flask was heated on the water bath to evaporate the solvents under vacuum, the blue solid gradual- ly turned to a white solid. The NMR spectrum of this solid consists of a singlet ( 67.79, 2H) and two doublets (66.62, 2H and 6.30, 2H, J =- 2Hz). It is an adduct between 34 and TCNE. In Compounds 5, 116 and 117 the c-fused thio- phene ring undergoes the cycloaddition reactions with di- enophiles. The Dials-Alder reaction results in restoring the benzenoid character of the carbocyclic rings. Hence the transition state in the first Diels-Alder reaction reflects this stabilization. With 34 this stabilization is not shown until the second Diels-Alder reaction, because the driving force does not exist in the first step. And of course in the process the aromaticity' of two thiophene moieties is lost. In 30, it is required to lose the aro- maticity of the three thiophene rings for' restoring' the endocyclic aromaticity of benzene ring. Thus, the addition- al thiophene rings reduce the diene character of 30. EXPERIMENTAL 1. General Procedures 1'H NMR spectra were measured on a Varian T-60 or on a Bruker WM-250 spectrometer with chemical shifts reported in 5 -units from tetramethylsilane as the internal standard. J'3C NMR spectra were determined on a Varian GET-20 spec- trometer or on a Bruker WEI-250 spectrometer. IR spectra were recorded on a Perkin-Elmer 167 Grating Spectrophoto- meter. UV spectra were determined on a Varian Cary-219 spectrometer. Mass spectra were obtained with a Finnigan 4000 spectrometer. High resolution mass spectra were obtain-’ ed with a Varian CHS spectrometer. The melting points were determined on a Thomas Hoover Unimelt apparatus and are uncorrected. 2. 4,5,6,7-Tetramethyl-l,3-dihydrobenzolc]thiophene (55) To a boiling solution of water (50 mL) and ethanol (50 mL) in a 1000-mL three-necked flask equipped with two addi— tion funnels and a condenser, bislchloromethy1)preh- niteness (2.329, 10 mmole) in 200 mL of ethanol and 72 73 NaZS.9H20 (3.69, 15 mmole) in 200 mL of water were added through the addition funnels at equal rates over 0.5 h. The mixture was refluxed for another 6 h and cooled-to room temperature. The mixture was evaporated under vacuum until about 250 mL of the solution was left. To this mix- ture, 300 mL of ice-water was added. The white precipitate was separated from the solvent by suction filtration and dried under air. It was recrystallized from ethyl acetate and cyclohexane to give 55 (760 mg, 40%), mp 144-146°C. lawn (60 MHz, cnc1 1 64.66 (s, 4H), 2.16 (s, 128); 3 13CMR (20 MHz, .cnc131 6 136.48, 133.75, 129.41, 38.43, 17.00, 16.39; IR (KBr) 2900(m), 1490(3), 1200(w), 1050(w), 890(w), 800(w), 750 cm‘l(w); mass spectrum, r_n_/e_ (rel. intensity) 192(78), 177(100), 162(16): high resolution mass spectrum: calculated m/_e_ for (3123165 , 192 . 09728; found: g/g 192.09692. 3. 4,5,6,7-Tetramethyl-l,3-dihydrobenzo[clthiophene-Z- oxide (56) (a) Oxidation with NaIO4 To a solution of 100 mL of water and ethanol in a 1:1 ratio were added 760 mg (4 mole) of 55 and 840 mg (4 mmole) of sodium periodate at room temperature. The mixture was stirred overnight. After evaporation of most of the 74 organic solvent, the aqueous solution was extracted with 100 mL of benzene. The organic layer was washed with water and dried over M9804. The organic solvent was evaporated under vacuum to give a white solid which was recrystallized from benzene and hexane to yield 680 mg (82%) of 56, mp 160-162 °c. lHMR (60 MHz, 00013) 64.08 (br, 43), 2.10 (br, 123); 13CMR (20 MHz, cpc13) 6135.34, 130.96, 59.18, 17.23, 16.10; IR (KBR) 2900(m), 1450 (s), 1390(3), 1410(w), 1200(w), 1130(w), 1020(8), aaorm), 850 cmfllma; mass spectrum, mfg (rel. intensity) 208(34), 191(7), 177(3), 160(100); high resolution mass spectrum: calculated m/g for Cleléos, 208.09219; found: g/g 208.09134. (b) Oxidation with NBS in aqueous acetone A solution of 720 mg (4 mole) of NBS in 30 mL of acetone and 10 mL of water was added to a 50 mL aqueous acetone solution containing 760 mg (4 mole) of 55. The solution was stirred for 30 min and evaporated under vacuum to leave 20 mL of aqueous solution which was extracted with 100 mL of benzene. The organic layer was dried over 14980 4 . The solvent was evaporated under vacuum . Recrystallization from benzene and hexane gave 740 mg (89%) of 56, mp 160-161 °c. 75 4. 4,5,6,7-Tetramethylbenzolclthiophene (57) (a) Dehydration of 56 with alumina A mixture of 56 (100 mg, 0.48 mole) and neutral alumina (120 mg; activity I, 70-230 mesh) was sublimed at ISO-160°C under 25 mm Hg pressure. The sublimate consist- ed of 30 mg (33%) of 57, mp 101-102 °c. 18:48 (60 MHz, CDC1) 67.28 (8, 23), 2.40 (s, 6 H), 2.20 (3, SH); 3 130M8 (20 M82, 0°C, 00013) 6138.59, 130.25, 123.65, 114.19, 16.47, 16.13; IR (KBr) 31001211, 2900(8), 1600(w), 1500(w), 1450(m), 1390(w), 795(w), 700 cm‘lcs); mass spectrum, m/g (rel. intensity) 190(100), 175(73): high resolution mass spectrum: calculated m/g for C12H14S, 190.08162; found: m/g 190.08153. (b) Dehydration of 56 with LDA and MeOH A solution of LDA prepared from 1.01 g (11 mole) of diisopropylamine in 10 mL of THF and 5.5 mL of n-BuLi (2.0 M) was added to a solution of 10 mL of THF containing 1.04 g (5 mmole) of sulfoxide 56 under argon at -20°C. The solution was stirred for 20 min at -20°C and then 1 mL of MeOH was added. The solution was extracted with .50 mL of ether. The organic layer was washed with water and dried over M9804. Evaporation of the solvent gave 760 mg (80%) 76 of 57, mp 98-99 °c. 5. The adduct of 57 and TCNE TCNE (64 mg, 0.5 mmole) in 10 m1. of benzene was added to a solution of 10 mL of benzene containing 57 (95 mg, 0.5 mole). The mixture was refluxed for 2 h and then the solvent was evaporated under vacuum to give a white solid which was recrystallized from benzene to yield 120 mg (76%) of the adduct, mp 160°C (dec.). lHMR (60 MHz, acetone- d6) 66.10 (s, 23), 2.42(S, 6H), 2.24(s, 68); 13cm (20 M82, acetone-d6) 6137.59, 139.98, 130.59, 113.53, 111.85, 64.49, 53.75, 16.79, 16.49; IR (KBr) 2960(3), 2250(w), 1450(8), 1380(m), 1280(3), 1070(3), 820(8), 780 085118); mass spectrum, m/g (rel. intensity) 190(100), 175(33), 128(78). 6. l-Methyl-l,3-dihydrobenzo[c]thiophene-Z-oxide (58) A solution containing 5 mole of LDA in 20 mL of THF was added to a solution of 760 mg (5 mole) of sulfoxide 4732 in 50 mL of THF over 30 min at -78°C under argon. The solution was stirred for another 20 min at -78°c, then 3 mL of methyl iodide was added at ~-78°c for 2 h and warmed to room temperature. The reaction was quenched with excess MeOH and extracted with 100 mL of 77 ether. The organic layer was dried over M9804 and evapo- rated under vacuum to remove the solvent. The residue was chromatographed on silica gel with ethyl acetate as eluent to give 750 mg (90%) of 58. 13MB (60 MHz, cpc13) 6 7.18 (br, 4H), 4.36 (d, J-14 Hz, 1H) 4.26 (q, J86.0 Hz, 13 1H), 3.97 (d, J=14 Hz, 1H), 1.60 ((1, 1186.0 Hz, 381; CMR ‘(20 MHz, CDC13) 5133.18, 129.18, 128.78, 126.42, 125.23, 125.15, 66.91, 56.24, 14.94; IR (neat) 3080(w), 2960(m), 1450(3), 1400(w), 1030(3), 760 cm-l(3); mass spectrum, m/_e_ (rel. intensity) 166(50), 149(9), 135(5), 117(100); high resolution mass spectrum: calculated mfg for CngoOS, 166.04524; found: g/g 166.04580. 7. 1 1,3-Dimethy1-1,3-dihydrobenzoIclthiophene-Z-oxide (59) LDA (6 mole) in 20 mL of THF was added slowly to a solution of 58 (960 mg, 6 mole) in 20 mL of THF at -20°C under argon. The solution was stirred for 20 min at -20°C and then 2 mL of methyl iodide was added. The mix- ture was stirred at -20°C for 2 h and then quenched with MeOH. The mixture was extracted with 100 mL of ether and the organic layer was dried over M9804. The solvent was removed by vacuum. The residue was chromatographed on sili- ca gel with ethyl acetate as eluent to give 740 mg (69%) of l 59, mp 40-42°c. HMR (60 MHz, cpc13) 67.18 (m, 4H), 78 13 4.10 (q, J86.0 Hz, 2H), 1.72 (d, J=6.0 Hz, 6H); CMR (20 MHz, CDC13) y6136.28, 129.02, 124.29, 63.37, 13.76; IR (KBr) 3050(w), 2980(m), 2960(m), 1500(3), 1050 (s), 770 cm-l(s); mass spectrum, m/g (rel. intensity) 180(46), 131(48), 117(100); high resolution mass spectrum: calculat- ed 1_n_/_e_ for Cloleos, 180.06089; found g/g 180.06151. 8. l,3-Dimethy1benzo[clthiophene (60) and its adduct 61 with TCNE (a) Dehydration of 59 with alumina The sulfoxide 59 (390 mg, 2.2 mole) and neutral alumina (800 mg; activity I, 70-230 mesh) were mixed and heated in a sublimer under 25 mm Hg pressure at 140-150 0C. 1m (60 MHz, CDC13) of the sublimate showed 234.0 Hz, 28), 6.17 (dd, 2H), 2.61 (s, GB). The sublimate was not stable, so TCNE (192 57.25 (dd, 51136.0 Hz, J mg, 1.5 mmole) was added to the solution of the sublimate in 30 mL of benzene. The mixture was stirred at room temper- ature for l h and the solvent was removed by vacuum to give, a solid residue. This solid was recrystallized from chloro- form to yield 200 mg (31%) of 61, mp 160°C (dec.). 18M8 (60 M82, cpc13) 67.30 (br, 48), 2.18 (s, 6H); 13cm (20 M82, 00013) 6143.73, 130.53, 122.86, 112.82, 111.36, 72.26, 60.35, 14.76; IR (KBr) 3080(w), 2960 (m), 79 2250(w), 1500(3), 780(3), 700 cm‘1181; mass spectrum, m/g (rel. intensity) 162(100), 147(20), 128(49). (b) Dehydration with LDA and MeOH A solution of 59 (270 mg, 1.5 mmole) in 20 mL of THF was treated with 3.0' mole of LDA in 10 mL of THF at -20°C under argon. The mixture was stirred at -20°C for 20 min and quenched with 1 mL of methanol. The mixture was extracted with 50 mL of ether and washed with water. The organic layer was dried over MgSO4 and then the solvent was removed under vacuum. lHMR (60 MHZ, CDC13) indicat- ed the residue contained the starting material and the product 60 in a 4:1 ratio. 9. 1,4,5,6,7-Pentamethy1benzoIc]thiophene-Z-oxide (63) A solution of 3 mole of LDA in 10 mL of THF was added slowly to a solution of 56 (624 mg, 3 mole) in 20 mL of benzene at 0°C under argon. The mixture was stirred at 0°C for 20 min and then methyl iodide (3 mL) was added. The solution was stirred for 2 h and then quenched with 1 mL of methanol. The mixture was extracted with 50 mL of chloroform and the organic layer was dried over MgSO4. Evaporation of the solvent under vacuum gave a solid which was chromatographed on silica gel with 5% of MeOH in ethyl acetate as eluent to yield 520 mg (78%) of 63, mp 142-144 80 °c. l8M8 (250 M82, c0c13) 64.42 (q, J=7.3 82, 18), 4.26 (d, J-l6 Hz, 1H), 4.00 (d, J-16 Hz, 1H), 2.26 (s, 33), 2.23 (s, 38), 2.21 (s, 68), 1.35 (d, J=7.3 82, 38); 13CMR (20 MHz, CDC13) 6 137.84, 135.70, .135.63, .131.58, .130.93, 130.70, 67.93, 56.55, 17.38, 16.71, 16.24, 15.00; IR (KBr), 2960(3), 1450(3), 1380(3), 1030 cm-l(s); mass spectrum, m/g (rel. intensity) 222(55), 208(20), 174(100); High resolution mass spectrum; calculated 3/3 for C13H1808, 222.10784; found: 222.10829. 10. l-Deuterio-4,5,6,7-tetramethylbenzolc]thiophene (71) To a solution of 56 (208 mg, 1 mole) in 10 mL of T8? was added 2 mole of LDA in 10 mL of THF at -20°c under argon. The mixture was stirred for 20 min and then 3 mL of MeOD was added to this mixture at -20°C. The reac- tion worked up as described in the analogouslpreparation of 57 to give 133 mg (70%) of 71, mp 101-102 °c. l8M8 (60 MHz, CDC13) 67.28 (s, 1H), 2.40 (s, 6H), 2.20 (s, 6H); mass spectrum, ‘m/g (rel. intensity) 191(100), 176(71). ll. 1,4,5,6,7-Pentamethy1benzo[clthiophene (72) and its TCNE adduct To a solution of 56 (624 mg, 3 mole) was added a solution of LDA (9 mole) in 20 mL of THF at -20°C under 81 argon. The solution was stirred at -20°C for 20 min and 3 mL of methyl iodide (480 mmole) was added. Workup as described in the preparation of 57 gave 400 mg (65%) of o 1 72, mp 68-69 c. HMR (60 MHz, cuc13) 66.92 (s, 1H), 2.92 (s, 3H), 2.50 (s, 6H), 2.17 (br, SH); IR (KBr) 3100(w), 2950(8), 1600(w), 1500(w), 1450(m), 1390 cm“1 (3); mass spectrum, m/_e_ (rel. intensity) 204(100), 189(42), 171(9); high resolution mass spectrum: calculated m/g for C 204.09728;. found: g/g 204.09374. 135165' Since the product 72 was not stable, TCNE (128 mg, 1 mole) was added to a solution of benzene (10 mL) contain- ing 72 (204 mg, 1 mole). The mixture was refluxed for 30 min and the solvent was removed by vacuum to give a solid. The solid was recrystallized from chloroform to give 278 mg (83%) of the. adduct, mp 158°C (dec.). 18M8 (250 M82, DMSO-ds) 66.18 (s, 18), 2.52 (s, 3H), 2.47 (s, 38), 2.45 (s, 3H), 2.25 (s, 6H); IR (KBr) 2960(3), 1500(3), 1395(3), 1260 cm_l(w); mass spectrum, m/g (rel. intensity) 204 (100), 190(2), 128(46). 12. An attempt to prepare 71 from 57 with LDA and MeOD LDA (2 mole) in 5 mL of THF was added to a solution of 190 mg (1 mole) of 57 in 10 mL of THF under argon at -20°C. The solution was stirred for 20 min and then 2 mL 82 of MeOD was added. The solution was stirred for another 5 min and then warmed up to room temperature. Workup as described in the preparation of 71, gave 170 mg of the recovered starting material 57. The mass spectrum and l HMR spectrum indicated that no deuterium was incorporat- ed into the thiophene ring. 13. HexamethylbenzoIclthiophene (65) and its TCNE adduct (73) To a solution of 400 mg (2 mole) of 72 in 15 m1. of THF was added 2.5 mL of n-BuLi (1.6 M) at -20°C under argon. After the solution was stirred at -20°C for 20 min, 3 mL of methyl iodide was added to the solution. The mixture was stirred at -20°C for another 2 h and warmed up to room temperature. Water (10 mL) was added and the_ mixture was extracted with 50 mL of ether. The organic layer was dried over MgSO and then the solvent was remov- 4 ed by vacuum to give 240 mg (55%) of 65, mp 115-116 °C (dec.). 18M8 (60 M82, c0c1 ) 152.76 (3, 68), 2.48 (s, 3 6H), 2.05 (s, 6H); mass spectrum, mfg (rel. intensity) 218(100), 203(46); high resolution mass spectrum: calculat- ed 3/3 for c 218.11293; found: 3/3 218.11536. 143183' The product was redissolved in ether. While ether was removed under vacuum at room temperature, the product was 0 1 converted to a dimer, mp 210-212 C. HMR (250 MHz, 83 CDC13) 66.47 (s, 18), 4.76 (q, J=6.9* 82, 18), 4.42 (d, J=6.9, 82, 18); 2.53 (s, 38), 2.33 (s, 6H), 2.29 (s, 38), 2.24 (s, 38), 2.20 (s, 38), 2.17 (s, 38), 2.15 (s, 38), 1.57 (d, J-6.9 82, 38), 1.47 (d, J-6.9 82, 38); 13CM): (20 M82, CDC13) 6142.94, 141.98, 141.28, 135.73, 134.91, 129.69. 129.20, 128.76,’62.76, 46.98, 46.19, 35.16, 26.67, 24.72, 18.95, 17.17, 16.84, 16.57, 16.40; mass ‘spectrunu m/g (rel. intensity) 436(11), 421(28), 218(100). TCNE (128 mg, 1mmole) was added to a solution of 65 (180 mg, 1 mole) in 20 mL of benzene. The solution was stirred overnight. Then the solvent was removed under vacuum to give a solid which was recrystallized from chloro- form to give 248 mg (80%) of 73, mp 160°C (dec.). l8M8 (CDC13, 250 M82) 62.44 (s, 68), 2.42 (s, 6H), 13 2.24 (3, 6H); CMR (CDCl 20 MHz) 6138.58, 137.40; 3’ 130.19, 111.15, 110.26, 72.41, 54.0, 19.98, 17.08, 16.36; IR (KBr) 2940(8), 1500(8), 1390(3), 1250 cm‘lw); mass spectrum my; (rel. intensity) 218(100), 205(1.6), 128 (24). 14. 5,6-Dimethyl-l,3-dihydrobenzo[clthiophene (74b) 65 Cyclization of the dichloride 4,5-bis(chlorome- thy1)-o-xylene 74a (10.5 g, 50 mmole) with Na28.9H20 (18 g, 75 mmole) was carried out as described in the prepa- ration of 55. Steam distillation gave 2.0 g (24%) of the 84 product (74b), mp 43-44°C. lHMR (60 MHz, CDC13) 13 5 6.92 (s, 2H), 4.18 (s, 4H), 2.20 (3, SH); CMR (20 MHz, CDC13) 6137.94, 125.94, 125.44, 37.84, 19.53, IR (KBr) 3010(w), 2900(8), 900 cm'1 (3); mass spectrum, m/g (rel. intensity) 164(100), 149(89), 134(10); high reso- lution mass spectrum: calculated m/g for C103125' 164.06598; found: m/g 164.06597. 15. 5,6-Dimethyl-l,3-dihydrobenzotc]thiophene-2-oxide (74c) The oxidation of 74b (2.0 g, 12 mole) with NBS (2.0 g, 12 mmole) in aqueous acetone solution was carried out as described in the synthesis of 56 to give 800 mg (37%) of 74c, mp 112-113 °C. l8M8 (60 M82, CDC13) 87.00 (s, 28), 4.23 (d, J=16 82, 28), 3.90 (d, J-16 82, 28), 2.15 (s, 68); 13cm: (20 _M82, CDC13) 6137.04, 132.06, 127.43, 59.12, 19.68; IR (KBr) 3040(w), 2940(3), 1500(m), 1020 cm-l(s); mass spectrum, m/g (rel. intensity) 180(70), 163(4.4), 132(100); high resolution mass spectrum: calculat- ed m/g for C OS, 180.06089, found: m/g 180.06151. 10312 16. 5,6-Dimethylbenzo[c]thiophene (74) and it TCNE ad- duct (74d) The procedure for dehydration of sulfoxide 74c- (180 mg, lmmole) with LDA (2 mmole) was the same as described in 85 the preparation of 57, and gave 130 mg (80%) of 74. 18148 (60 m2, CDC13) 67.40 (s, 28), 7.32 (s, 28), 2.26 (s, 63). Since the product was not stable, TCNE (100 mg, 0.8 mmole) was added to a solution of 74 (130 mg, 0.8 mmole) in 20 mL of benzene. Evaporation of the solvent by vacuum distillation gave a solid which was recrystallized from chloroform to yield 230 mg (79%) of the adduct 1 (74d), mp 160 (dec.). HMR (60 M82, CDC13) 6 7.27 (s, 28), 5.27 (3, 28), 2.30 (s, 68); l3CMR (20 M82, cpc13) 5 138.94, 125.81, 113.95, 111.95, 65.18, 54.05, 19.90; IR (KBr) 3010 (w), 2920 (s), 2250(w), 1500 om‘l(s). l7. Benzo[c]thiophene (5) and its TCNE adduct The procedure for dehydration of sulfoxide 47 (152 mg, 1 mole) with two molar equivalents of LDA was the same as described for the preparation of 57. After removal of ~the solvent, the product 5 was dissolved in 10 mL of benzene and TCNE (128 mg, 1 mole) was added. The mixture was refluxed for 1 h and then the solvent was removed under vacuum to give a solid which was recrystalized from CHC13 45 to yield 220 mg (84%) of the adduct, mp 160°C (dec.). l8M8 (60 M82, CD CN) 67.17 (m, 48), 5.62 (s, 28). 3 86 18. Naphtho[l,2-c1thiophene (35) Dehydration of the sulfoxide 7632 (202 mg, 1 mole) with LDA (2 mole) was carried out as described for the synthesis of 57. Workup followed by chromatography on. silica gel with petroleum ether as eluent gave 160 mg (87%) 32 '110-112OC). 1am: (60 of 35, mp 108-109°C (lit. m2, CDC13) 66.90-8.00 (m, 8H); mass spectrum, _m/g (rel. intensity) 184(100), 152(7.0). 9 19. Naphtho[2,3-clthiophene (78)4 and its TCNE adduct (79) Dehydration of the sulfoxide 7749 (202 mg, l mmole) with LDA (2 mmole) as described for the synthesis of 57 gave an orange solution. To this orange solution TCNE (128 mg, 1 mole) was added. The mixture was stirred at room temperature overnight and then the solvent was evapo- rated under vacuum to give a brown solid which was chromato- graphed on silica gel with 10% petroleum ether in ethyl acetate as eluent to yield 90 mg (28%) of 79, mp 160°C (dec.). 18M8 (60 M82, acetone-d6) (58.0 (s, 28), 7.90 (m, 2H), 7.51 (m, 2H), 6.18 (s, 2H); IR (KBr) 3015(3), 2250(w), 1500(3), 890(3), 765(5), 650 cm'1(s). 87 20. 4,5,6,7,8,9-Hexamethyl-1y3-dihydronaphtho[2,3-clthio- phene (81) The dichloride 8067 (2.0 g, 6.5 mmole) in 50 mL of TH]? and Na28.9H20 (2.4 g, 10 mole) in 50 mL of water were added simulataneously with stirring over 30 min to a boiling solution of ethanol (50 mL) and water (50 mL) in a three-necked flask equipped with two addition funnels and a condenser. The nuxture was stirred at reflux overnight and then cooled to room temperature. The organic solvent was evaporated under vacuum to leave about 150 mL of the mix- ture. Water (150 mL) was added and the aqueous solution was filtered. The solid was washed'with water and dried under air. It was submitted to chromatography on silica gel with 5% of ethyl acetate in hexane as eluent. The pure product was recrystallized from methanol to give 500 mg (29%) of .81. mp 110-112 °c. lHMR (60 MHz, CDCl) 64.23 (s, 3 13C148 (20 M82, CDC13) 5137.23, 135.29, 133.53, 129.14, 126.60, 37.69, 21.66, 43), 2.44 (s, 128), 2.26 (s, 63); 21.59, 17.00; IR (KBr) 2900(8), 1480 (w), 1200(w),, 780 cm-l(w); mass spectrum, m/g (rel. intensity) 270 (100), 255(61), 240(32); high resolution mass spectrum: calculated m/g for ClBHZZS' 270.14423; found: m/g 270 .14580 . 88 21. 415,6,7,8,9-Hexamethy1-1,3-dihydronaphthol2,3-c1thio- phene-Z-oxide (82) The procedure for oxidation of 81 (810 mg, 3 mole) with NBS (540 mg, 3 mole) in aqueous acetone solution was the same as described in the preparation of 56. The crude product 82 was recrystallized from methanol to afford 570 mg (66%) of 82, mp 175-176 °c. 13MB (60 M82, CDC13 64.20 (br, 48), 2.45 (br, 128), 2.30 (s, 68); l3CMR (20 ) MHz, CDC13) 6135.86, 134.18, 131.44, 129.34, 129.00, 58.94, 22.00, 21.55, 17.04; IR (KBr) 2900(3), 1480(m), 1380(m), 1080 cm-l(s); mass spectrum, m/g (rel. inten- sity) 286(50.4), 269(26.3), 238(100); high resolution mass spectrum; calculated 81/3 for (21832208 , 286 . 13 914; found: 51/3 286 .13912 . 22. 4,516,7,8,9-Hexamethylnaphtho[2,3-c1thiophene (83) and its TCNE adducts (84, 85) Aromatization of the sulfoxide 82 (286 mg, 1 mole) with LDA (2 mole) was carried out by the same procedure as described in the synthesis of 57, and gave an orange solu- tion of 83. TCNE (128 mg, 1 mole) was added to the solu-. tion. The mixture was stirred at room temperature over- night. The solvent was evaporated under vacuum to give a residue which was chromatographed on silica gel with 50% ethyl acetate in petroleum ether. Two adducts (84, 85) 89 of TCNE were isolated in 27% yield. Compounds 84 and 85 were formed in a 8:1 ratio. For 84: mp 205°C (dec.); l8M8 (60 M82, CDC13) «57.27 (s, 23) 2.60 (S, 63), 2.55 (3, 63), 2.20 (s, 63); IR (KBr) 1 3100(w), 2920(3), 2250(w), 1000 cm- (111); mass spectrum, g/g (rel. intensity) 268(100), 255(48), 236 (31), 128 (71). For 85: mp 210°C (dec.); l8M8 (60 M82, CDC13) 65,48 (3, 28) 2.66 (s, 68), 2.48 (s, 68), 2.30 (s, 68); 13cm (20 MHz, CDC13) 6138.45, 136.75, 132.81, 131.11, 128.81, 111.76, 110.05, 63.95, 53.71, 29.78, 29.48, 22.37; IR (KBr) 2960(3), 2940(3), 2250(w), 1500(m), 1390 cm'1(m); mass spectrum, m/g (rel. intensity) 268(100), 236(43), 128 (53). 23. 1,3-Dihydrophenanthrol9,10-clthiophene (88a) A solution of potassium hydroxide (570 mg, 10 mole) in 200 mL of ethanol and 10 mL of water was added over 1 h m: a boiling solution of 88 (1.8 g, 5 mmole) and thioacet- amide (380 mg, 5 mole) in 500 mI. of benzene and 200 mL of ethanol. The solution was refluxed overnight and cooled to room temperature. The solvent was removed by vacuum and the residue was extracted with benzene (100 mL). The organic layer was washed with water and dried over MgSO Then 4. 90 the solvent was removed by evaporation under vacuum. Recrys- tallization from benzene and hexane gave 450 mg (38%) of 50 1 88a, mp l75-177°C (lit. lea-181°C). HMR (60 MHz, CDC13) 6 6.9-8.1 (m, 8H), 4.0 (s, 4H); mass spec- trum, m/g (rel. intensity) 236(100), 202(21). 24. 1,3-Dihydrophenanthro[9,10-c]thiophene-2-oxide (87) The procedure for oxidation of 88a (450 mg, 1.9 mmole) with NBS (360 mg, 2 mmole) in aqueous acetone solu- tion was the same as described for the preparation of 56. Recrystallization from benzene and hexane gave 250 mg (53%) 50 1 of 87, mp 211-214°C (lit. , 215-216°C). HMR (250 M82, CDC13) 67.3-7.9 (m, 8H), 4.65 (s, 4H); mass spectrum, m/g (rel. intensity) 252(29), 235(33.6), 204 (100). 25. PhenanthroL9,10-cIthiophene (33) The procedure for dehydration of the sulfoxide 87 (250 mg, 1 mole) with LDA (2- mole) was the same as de- scribed in the synthesis of 57. The residue obtained from workup was chromatographed on silica gel with benzene as eluent to give 120 mg (51%) of 33, mp 163-164°C (lit.50 1 168-169°C). HMR (250 M82, CDCl ) 67.20- 8.40 (m); mass 3 spectrum, m/g (rel. intensity) 234(100), 202(21). 91 26. 3,4-Dibromo-2,5-dihydrothieno[3,4-clthiophene (97) 64 The procedure for cyclization of 97a (4.3 g, 10 mole) with Na28.9H20 (3.6 g, 15 mole) in methanol (300 mL) was the same as described for the preparation of the sulfide 55. Workup gave a residue which was recrystal- lized from methanol to yield 600 mg (20%) of 97, mp 67- 55 1 68°C (lit. 67-68°C). HMR (60 M82, CDCl ) 63.84, mass 3 spectrum, m/e (rel. intensity) 302(58), 300 (100), 298(50), 221(53) , 219(54) . 27. 2,5-Dihydrothieno[3,4-c]thiophene (96a) n-BuLi (5 mL, 2.4 M) was added to a solution of 1.5 g (5 mole) of 97 in 50 mL of ether at -78°C under argon. The solution was stirred at -78°C for 20 min and quenched with 5 m1. of methanol. After being warmed up to room tem- perature, the ether layer was washed with water and dried over M9804. The solvent was removed. Recrystallization of the residue from hexane gave 650 mg (92%) of 96a, mp 60- 54 1 61°C (lit. 60-62°C). HMR (60 M82, CDCl )6 6.60 (s, 28), 3 3.86 (s, 43). 28. 2,5-Dihydrothienol3,4-clthiophene-1-oxide (96b) The procedure for oxidation of sulfide 96a (545 mg, 4 mole) with NaIO4 (856 mg, 4 mole) was the same as 92 described for the preparation of 56, and gave an oil which was chromatographed on silica gel with 5% of MeOH in ethyl acetate to yield 300 mg (48%) of 96b, mp 123- 124°C. l8M8 (60 M82, CDC13) 6 6.94 (s, 28), 4.12 (d, J-ls 82, 28), 3.71 (d, 28); 13cm (20 M82, CDC13) 6137.89, 119.62, 53.76; IR (KBr) 3100(w), 2980(w), 2900(w), 1 1370(m),, 1020(3), 800 cm- (3); mass spectrum, m/_e_ (rel. intensity) 158 (100), 141(54), 110(96); high resolu- ti on mass spectrum; calculated m/g for C H OS 66 2' 157.98601, found: p/g 157.98605. 29. An attempt to trap thieno[3,4-c]thiophene (17) with DMAD LDA (3 mole) in 20 mL of THF was added to a solution of THF (20 mL) containing the sulfoxide 96b (240 mg, 1.5 mmole) and dimethyl acetylenedicarboxylate (420 mg, 3 mole) at -78°C under argon. The mixture was stirred at -78°C for 20 min and then quenched with MeOH (2 mL). The reaction mixture was warmed up to room temperature and‘ stirred overnight. Ether (50 mL) was added and the solution was washed with water. The organic layer was dried over MgSO4 and evaporated to remove the solvent under vacuum. The residue was submitted to chromatography. No adduct of 17 and DMAD was isolated. 93 30. 3,4-Dibromo-2,5-dihydrothieno[3,4-c1thiophene-1-oxide (98) Oxidation of the sulfide 97 (1.2 g, 4 mole) with NBS (720 mg, 4 mole) in aqueous acetone solution was carr- ied out in the same way as described in the preparation of 56. Recrystallization of the crude product from methanol gave 1.2 g (95%) of 98, mp 139-140°C. lHMR (60 £2, CDC13) 64.03 (d, J=16, Hz, 28), 3.68 (d, 28); 13cm (20 M82, CDCl) 6139.68, 106.37, 55.11; IR (KBR) 2960(w), 3 1580(m), 1500(m), 1410(m), 1350(m), 1060(3), 960cm-1(m); mass spectrum, m/g (rel. intensity) 318(20.4), 316 (36), 314(17.3), m/g for C H Br 4 2OS 315 .805171; found: m/g 6 2’ 315.806058. 31. 2,5-Dibromothieno[314-c1thiophene (99) and dimethyl lyg-dibromobenzoEclthiophene-S,6-dicarboxy1ate (101) To a solution of THF (25 mL) containing the sulfoxide 98 (632 mg, 2 mole) and dimethyl acetylenedicarboxylate (l g, 7 mole) was added LDA (4 mole) in 15 mL of THF at -20°C under argon. After the solution was stirred for 20 min MeOH (2 mL) was added at -20°C. The mixture was stir- red at room temperature overnight and then extracted with CHCl (50 mL). The organic layer was washed with water 3 and dried over MgSO4. The solvent was removed undervacuum to give a solid which was chromatographed on silica gel 94 with 5% of hexane in chloroform as eluent to yield 15 mg (2%) of 101, mp 157-158°C. 1314R (60 M82, CDCl) 3 67.90 (s, 23), 3.94 (s, 6H); 13CMR (62.9 MHz, CDC13) 6167.76, 135.94, 126.51, 122.83, 107.72, 53.44; mass spec- trum, my; (rel. intensity) 410(57.1), 408 (100), 416 (47.8), 379(60), 377(93) 375(46); high resolution mass spectrum: calculated m/g for C12H8Br204s, 405.85111; found: Q/g 405.85111. 32. 3,4-Diphenylthiophene (112) Dehydration of the sulfoxide (111)57 (250 mg, 1 mole) with two equivalents of LDA at -20°C was carried out in same way as described in the synthesis of 57. Wbrk- up gave a brown oil which was submitted to GC-Mass spectro- 'metry with a 20% 5830 column at 180°C to give the mass spectrum of 112. Mass spectrum,58 m/g (rel. intensi- ty) 236 (100), 221(16), 202(17). The product was formed in low yield. 33. 143,4,6-Tetrahydrobenzo[1,2-c:3L4-c'Idithiophene- 2,5-dioxide (121) Sodium periodate (860 mg, 4 mole) in 50 mL of water was added to a solution of methanol (200 mL) containing 62 120 (400 mg, 2 mmole). The solution was stirred at 95 room temperature for 12 h and then filtered. to remove inorganic salts. The filtrate was evaporated under vacuum to give a residue which was chromatographed on silica gel with 20% methanol in ethyl acetate as eluent. The crude pro- duct was recrystallized from methanol to give 340 mg (75%) of 121, mp '202-204°C. 1HMR (250 MHz, acetone-d ) 6 67.40 (s, 28), 4.20(m, 88); l3CMR (20 M82, MeOD) 6137.7, 135.4, 127.6, 60.1, 58.8; IR (KBr) 3000(W), 2950(W), 1450 (m), 1380(m), 1020 cm-l(s); mass spectrum, my; (rel. intensity) 226(100), 208(2), 178(8); high resolution mass spectrum: calculated m/g for C103100282' 226.01223; found: m/g 226.01092. 34. Benzo[l,2:c-3,4:c'ldithophene (34) (a) Dehydration of 121 with Alumina The disulfoxide 121 (226 mg, 1 mole), mixed with neutral alumina (400 mg, activity' I, 70-230 mesh), was sublimed at 140-150°C at 25 Torr to give 120 mg (63%) of 33 1 34, mp 108-110 °C (lit. llo-111°C). HMR (60 M82, CDC13) 67.70 (d, J=2.7 Hz, 28), 7.46 (d, J=2.7 Hz, 2H), 7.11. (s, 2H); mass spectrum“ ‘m/g’ (rel. intensity) 190(100), 158(4), 145 (13). 96 (b) An attempt to aromatize 121 with LDA Treatment of the disulfoxide 121 (226 mg, 1 mole), in 15 mL of THF with LDA (4 mole) as described in the preparation of 57 gave a mixture which could not be resolved. 35. Bromination of 34 with bromine Bromine (41 mg, 0.26 mole) in 5 mL of CC14 was added to a solution of 34 (50 mg, 0.26 mmole) in 10 mL of CCl4 at 0°C to give a purple solution. The solution was stirred at 0°C for 30 min and then washed with saturated sodium bisulfite solution , sodium chloride solution , and water. The organic layer was dried over M9804 and evapo— rated to give unidentified products. 36. Bromination of 34 with one equivalent of NBS To a solution of 34 (380 mg, 2 mole) in 20 mL of acetic acid was added over 30 min a solution of acetic acid (60 mL) containing NBS (360 mg, 2 mole). The mixture was stirred at room temperature for another 30 min. Water ( 200 mL) was added and the mixture was extracted with 100 mL of ether three times. The combined organic layer was washed with sodium bicarbonate solution and water, and dried over MgSO The solvent was removed by distillation to give a 4. 97 brown solid. The solid was chromatographed on silica gel with hexane as eluent to give 42 mg (6%) of 1,3-dibromo- benzo[l,2-c:3,4-c'1dithiophene (125), mp 120-122°C. 18M8 (250 M82, CDC13) 68.55 (dd, J1=3.o 82, J2=0.9 Hz, 13), 7.48 (d, J=3.0 Hz, 13), 7.13 (dd, J1=10 Hz, 13 J2=0.9 Hz, 13), 6.95 (d, J=10 Hz, 111); CMR (62.9 MHz, CDC13) 6136.70, 130.64, 130.41, 122.29, 121, 119.53, 119.18, 118.35, 105.77, 104; IR (KBr) 3100(w), 1430(w), 1390(w), 1195(w), 1020(m), 860(w), 800 cm‘1(s); mass spec- trum, m/g (rel. intensity) 350(60), 348(100), 346(50), 269(35), 267(28); high resolution mass spectrum: calculated 111/g for C103 Br 347.80576; found: _m/_e_ 347.80645. 422' The second fraction yielded 380 mg (70%) of the mono- bromo isomers 123 and 124 in a 1:1 ratio. Pure 123 could be obtained by washing the mixture with hexane. For 123:13MR (250 M82, CDC13) 67.75 (dd, J1=3.l 82, J2=0.9 Hz, 13), 7.71 (d, J=0.6 Hz, 13), 7.50 (d, J=3.1 2=0.9 82, 18), 7.04 (dd, Jl=10 Hz, Jé=0.6 82, 18). For 124; 18M8 (250 M82, CDC13) 68.59 (dd, J1=2.8 Hz, J2=0.9 Hz, 13), 7.46 (d, J=2.8 Hz, 13), 7.39 (s, 13), 7.08 (dd, J1=9.5 Hz, 32, 13), 7.18 (dd, J1=10 Hz, J J2=0 . 9 Hz , 1H) , 6 . 99 (d, J=9 .5 Hz, 1H); mass spectrum of this mixture m/_e_ (rel. intensity) 270(100) , 268 ( 84) , 189(31); high resolution mass spectrum: calculated m/g for C H BrS 269.89969; found: m/g 269.89941. 10 5 2' 98 37. Bromination of 34 with three equivalents of NBS To a suspension of 34 (190 mg, 1 mole) in 20 mL of acetic acid was added NBS (540 mg, 3 mole). The mixture was stirred at room temperature for 30 min and then water (200 mL) was added to the mixture. A yellow solid precipi- tated and was collected on a suction funnel. Recrystalli- zation from CHC13 gave 210 mg (48%) of 126, mp 157- 158°C. l8M8 (250 MHz, CDC13) 68.51 (s, 18), 7.10 (d, J=9.5 Hz, 13), 7.03 (d, 13); IR (KBr) 3100(w), 1350(w), 1200(m), 1120(w), 1030(w), 980(w), 790 cm‘l(s); mass spec- trum, Eye (rel. intensity) 430(12), 428(30), 426(26), 424(9), 348(6), 346(13), 344(5); high resolution mass spec- trum: calculated m/_e_ for CloH Br 427.71855; found: m/g 332' 427.71691. 38. Bromination of 34 with four equivalents of NBS Tetrabromide (127) was obtained by a similar proce- dure as above but with four equivalents of NBS. Compound 34 (190 mg, 1 mole) gave 150 mg (30%) of 127, mp 208- 210°C, which was recrystallized from chloroform. 1HMR (250 MHz, CDC13) 67.00(s); IR (KBr) 3100(w), 1370(m), 1280(m), 1120(m), 1010(m), 920(m), 860(m), 790 cm'1(s); mass spectrum, m/g (rel. intensity) 510(17), 508(73), 506(99), 504(65), 502(16), 428(65),.426(100), 424(72), 422 99 (19), 348(38), 346(66), 344(33); high resolution mass spec- trum: calculated m/g for C10H23r432, 505.62942; found: m/g 505.63018. 39. 3,4,5,6-Tetrakis(bromomethyl)-l,2-dibromobenzene (128) Dibromoprehnitene (2.92 g, ‘10 mole) and bromine (6.4 g, 40 mole) in 150 mL of CC14 were irradiated with a 200 watt lamp under reflux for one day. The solution was washed successively with aqueous sodium bisulfite and sodium bi- carbonate. The organic layer was washed. with water and dried over M9804. The solvent was removed by vacuum evapo- ration to give a solid, which was recrystallized from hexane to give 5.00 g (82%) of the desired product, mp 187- 188°C. l8M8 (60 M82, CDC13) 64.70 (s, 48), 4.52 (s, 48); 13cm (20 MHz, CDC13) 6139 .46 , 137 .23 , 113.23 , 30.96, 24.91; IR (CCl ) 2960(w) , 1500 cm'1(e); mass 4 spectrum, m/g (rel. intensity) 610(0.5), 608(0.8), 606 (0.5), 533(1.4), 531(95), 529(19.1), 527(18), 529(9), 525 (1.5). 40. 7,8-Dibromobenzo[1,2-c:3,4-c')dithiophene (130) The sulfide (129) was prepared from 128 according to the method used to prepare 120. The sulfide (129) was not purified because of its low' solubility. It was directly dehydrogenated with two molar equivalents of DDQ. 100 The crude sulfide 129 ,(1 g, 3 mole) and DDQ (1.43 g, 6 mmole) were refluxed in chlorobenzene (150 mL) for 3 h. The solvent was distilled under vacuum. The brown residue was chromatographed on basic alumina with benzene as eluent to give 110 mg (11%) of 130, mp 167-169°C. lHMR (250 MHz, CDC13) 67.85 (d, J=3.2 Hz, 2H), 7.75 (d, 2H); 13CMR (62.9 M82, CDC13)6136.34, 130.46, 123.28, 118.34, 117.75; IR (KBr) 3100 cm-l(s); mass spectrum, m/_e_ (rel. intensity) 350(64.9), 348(100), 346(49.9); high reso- HBr lution mass spectrum: calculated 9/2 for C10 4 2 82, found: m/g 347.80645. 41. Bromination of 130 with four equivalents of NBS Dibromobenzodithiophene 130 (20 mg, 0.06 mole) was brominated with NBS (45 mg, 0.24 mmole) in acetic acid (20 mL) by the same procedure used for the preparation of 127. After workup, the residue was recrystallized from C8Cl3 to yield 25 mg (71%) of 132, mp 210—211°c. l8M8 (250 M82, CDC13) 68.72(s); IR (KBr) 3100 cm"1 (w); mass spectrum» ‘m/g. (rel. intensity) 590(0.20), 588 (11.6), 586(21.8), 584(22), 582(12), 580(0.24); high reso- lution mass spectrum: calculated m/g for C HBr 10 5 2' 583.53998; found: m/g 583.53613. 101 42. l,6-Diformylbenzo[l,2-c:3,4-c']dithiophene (135) To a solution of 34 (380 mg, 2 mole) in 20 mL of dry TMEDA was added n-BuLi (1.6 M, 2.5 mL) at -25°C under argon with stirring. The solution was stirred for l h at -25°C and then was quenched by DMF (5 mL) at ~25°C. Stirring was containued for another 2 h, then the mixture was warmed to room temperature. Water (10 mL) was added and the solution was extracted with ether (200 mL). The organic layer was washed with dilute hydrochloric acid and water, then dried over M9804. Evaporation of the solvent gave an orange solid which was subjected to column chromatography (silica gel) with 30% of ethyl acetate in hexane as eluent. It gave 140 mg (29%) of 135, mp l70-l7l°C. lHMR (250 MHz, CDC13) 610.17 (3, 2H), 8.34 (s, 2H), 8.14 (s, 2H); 13CMR (20 M82, CDC13) 6181.29, 136.70, 133.13, 126.83, 122.27, 119.46; IR (KBr) 3080(m), 2900(w), 1650(3), 1450 (m), 1350 (m), 1250(m), 1200(m), 1100(w), 800(m), 690 cm-l(m); mass spectrum, m/g (rel. intensity) 246 (100), 217(29), 203 (18); high resolution mass spectrum: calculated m/g for C10H60282 , 245 . 98093; found : m/g 245.98068. 43. Charge-transfer complexes of 34 To a solution of 34 (19 mg, 0.1 mmole) in 10 mL of benzene was added TCNE (25.6 mg, 0.2 mmole) in 10 mL of 102 benzene to give a blue solution. Evaporation of the solvent left a dark blue solid, mp 187-189 °C (dec.). The IR and mass spectra were a composite of the spectra of 34 and TCNE. The visible spectrum showed a C-T band (CHC13) Amax 607 um (3:45). The C-T complex of 34 with TCNQ (1 eq.) was similar- 1y prepared. The complex melted at 175-180°C (dec.) and showed a C-T band (CHC13) at lmax 627 nm ( 8=52). 44. Adduct of 34 and TCNE To a solution of 34 (190 mg, 1 mole) in 50 mL of benzene was added 256 mg (2 mole) of TCNE in 50 mL of benzene. Evaporation of the benzene gave the dark blue charge-transfer complex. Chloroform (50 mL) and acetone (50 mL) were added to the solid. The mixture was heated on steam bath till the blue color changed to yellow. The solvent was removed by vacuum distillation to give a yellow solid which was chromatographed on silica gel with 50% of chloroform in acetone as eluent to. afford 300 mg (67%) of the adduct (156), mp 160°C (dec.). l8M8 (250 M82, acetone-dG) 67.79 (s, 2H), 6.62 (d, J=l.9 Hz, 2H), 6.30 (d, 28); l3CMR (20 M82, acetone-d6) 6151.09, 144.90, 133.95, 121.38, 120.30, 120.11, 73.17, 71.20, 61.94, 61.80; IR (KBr) 3010(m), 2940(w), 2260(w), 1500(w), 810 cm‘l(s); mass spectrum, m/g (rel. intensity) 190(100), 158(4), 145(14), 128(57). 103 45. Bromination of naphtho[l,2-c1thiophene (35) (a) With bromine Bromine (320 mg, 2 mole) in 5 mL of chloroform was added to a solution of 35 (180 mg, 1 mole) in 10 ml. of chloroform. The mixture was stirred at room temperature for 2 min and then was washed with aqueous sodium bisulfite, sodium bicarbonate and water. The organic layer was dried over M9304 and the solvent was removed under vacuum. The residue was chromatographed on silica gel with 30% of benzene in hexane as eluent to give 140 mg (41%) of 140 which could be recrystalized (from hexane, mp 89-91°C. 1 HMR (250 MHz, CDCl )‘(5 9.25 (m, 13), 7.65 (In, 13), 7.52 3 (m, 23), 7.28 (d, J=10 Hz, 13), 7.27 (d, J=10 Hz, 13); 13cm (62.9 M82, CDC13) 6132, 131.53, 128.64, 128.06, 127.88, 127.59, 127.11, 127.06, 123.65, 119.41, 104.94, 103.24; mass spectrum, mpg (rel. intensity) 344(35), 342(57), 340(28); high resolution mass spectrum; calculated m/g for C1236Br28' 341.85383; found: m/g 341.85412. (b) With two equivalents of NBS NBS (360 mg, 2 mole) was added to a solution of 35 (180 mg, 1 mole) in 20 mL of acetic acid. Workup as described for the preparation of 123 gave a solid. The solid was chromatographed on silica gel with 20% of benzene 104 in hexane as eluent to give 74 mg (22%) of 140. Compound 140 was recrystallized from hexane, mp 89-91°C. In addition to 140, compounds 141 and 142 were isolated in 13% and 21% yields. 142: mp 113-114°C; l8M8 (250 M82, CDC13) 68.97 (m, 18), 8.10 (m, 18), 8.09 (d, Jae 82, 18), 7.85 (m, 28); 7.81 (d, J=8 82, 18); 13CMR (62.9 M82, CDCl) 6189.18, 3 148.42, 137.49, 133.10, 129.58, 129.52, 129.25, 127.66, 127.37, 126.70, 118.27, 44.43; IR (KBR) 3080(w), 1700(3), 1500(m), 1350 cm-l(m); mass spectrum, my; (rel. in- tensity) 360(0.78), 358(1.6), 356(0.73), 279(73.6), 177 (77.4); high resolution mass spectrum; calculated m/e for C12H6Br208, 357.84875; found: m/g 357.8460? 141; mp 115-117°C; 18148 (250 M82, CDC13) 69.17 (m,. 18), 8.23 (d, J=8.5 82, 18), 7.95 (m, 18), 7.94 (d, J=8.5 Hz, 18), 7.77 (m, 28); 13C182 (62.9 M82, CDCl) 6190.50, 3 190.04, 139.46, 136.84, 136.17, 133.55, 130.67, 129.58, 128.53, 128.14, 126.20, 118.53; IR (KBR) 3060(m), 1690(3), 1400(w), 1250 cm-l(w); mass spectrum, m/g (rel. intensi- ty) 214(79.6), 186(31), 158(20), 126(100); high resolution mass spectrum: calculated m/g for C12H6028, 214.00885; found: m/g 214.00907. 105 46. Conversion of 142 to 141 A mixture of 142 (40 mg, 0.11 mole) and NBS (20 mg, 0.11 mole) in 10 m1. of acetic acid was stirred at room temperature for 30 min and worked up as described in the previous experiment. The residue was chromatographed on silica gel with 20% of benzene in hexane as eluent to give 10 mg (43%) of 141 and 15 mg (38%) of 142. 47. Hydrolysis of 141 to naphthalene-l,2-dicarboxylic acid (141a) Compound 141 (30 mg, 0.14 mole) was suspended in 30 mL of hydrochloric acid (20%) and the mixture was reflux for 6 h. After the solution was cooled to room temperature, it was extracted with 25 mL of ether. The organic layer was washed with water .and dried over MgSO4. The solvent was evaporated to give a yellow solid which was recrystallized from chloroform to give 15 mg (50%) of 141a, mp 175- 66 17 6°C (lit . 175°C) . Mass spectrum, m/g (rel . intensity) 216(29), 198(81), 172(10), 154(65.6), 126(100). 48. 1,2,3,4-Tetrakis (bromomethyl)naphtha1ene (146) A solution of 5.5 g (30 mole) of 14567 and 22.4 g (120 mole) of NBS in 100 mL of CCl4 was refluxed with stirring overnight in the presence of a trace of benzoyl 106 peroxide. The mixture was filtered after being cooled to room temperature. The filtrate was washed with water and dried over MgSO4. The solvent was removed under vacuum to give a solid. The solid was recrystallized from hexane to yield 12 g (80%) of 146, mp 193-194°C. l8M8 (60 M82, CDC1)58.0(m, 23), 7.50 (m, 23), 4.98 (S, 43), 4.80 (s, 3 48); 13CMR (20 MHz, CDC13) 6135.23, 133.47, 131.76, 128.17, 124.59, 25.85, 25.20; IR (KBr) 3030(w), 2950(m), 1450 cm'1(s); mass spectrum m/g (rel. intensity) 502 (2.2), 500(3.7), 498(2.3), 423(1l.6), 421(38.6), 419 (37.6), 417(12.3). 49. Naphtho[l,2-c:3,4-c']dithiophene (32) 1,3,6,8-Tetrahydronaphtholl,2-c:3,4-c'Jdithiophene (147) was prepared according to the procedure described 62 for the preparation of 120. Compound 147 was dehy- drogenated directly without purification because of its low solubility in any solvent. Compound 147 (1.0 g, 4 mole) and DDQ (2.0 g, 8 mole) were refluxed in 150 mL of chlorof- benzene for 4 h. The solvent was removed under vacuum. The residue was chromatographed on basic alumina with benzene .as eluent to yield 50 mg (5.1%) of 32, mp 167-168°C. l8M8 (250 M82, CDC13) 68.80 (dd, Jl=632, J2=232, 23), 7.91 (d, J=3Hz, 23), 7.70 (d, J=3Hz, 23), 7.43 (dd, J1=GHz, J2=ZHz, 28); 13CMR (62.9 M82, CDC13) 6135.46, 130.31, 127.95, 127.35, 124.42, 117.73, 117.03; IR 107 (KBr) 3100(w), 1450(8), 750 cm‘l(s); UV(CH3CN) 1 max 288 nm (586400), 270 (sh, 6200), 250(23000), 2489 (sh, 21000), 206 (sh, 10000); mass spectrum, m/g (rel. inten- sity) 240(100), 208(6.l); high resolution mass spectrum: calculated m/g for C14H8S2, 240.00675; found: m/g 240.00823. 50. Bromination of naphtho[l,2-c:3,4-c']dithiophene (32) Compound 32 (20 mg, 0.08 mole) in 5 mL of acetic acid was treated with NBS (60 mg, 0.32 mmole) and the mix- ture was worked up as described in the preparation. of 132. The residue was recrystallized from hexane to give 35 mg (91%) of 151, mp 148-150°C. 18M8 (250 M82, CDC13)«69.22 (m, 1H), 9.17 (m, 1H), 8.71 (s, 1H), 7.50 (m, 2H); mass spectrum" .E/E. (rel. intensity) 480(17.8), 478(37.6){ 476(34.8), 474(12.1); high resolution mass spec- trum: calculated m/g for C14H5Br3 2, 475.73647; found: m/g 475.73413. 51. Bromination of phenanthro[9,10-clthiophene (33) Bromination of 33 (85 mg, 0.36 mole) with NBS (150 mg, 0.72 mmole) in 30 mL of acetic acid was carried out as described for the preparation of 151. Workup gave a solid which was recrystallized from hexane to yield 100 mg (65%) of 148, mp 170-172°c. lHMR (250 M82, CDC13) 69.33 (m, 28), 8.40 (m, 28), 7.55 (m, 48); 13CMR (62.9 M82, 108 CDC13) 6131.79, 130.55, 127.97, 127.67, 127.09, 124.32, 123.44, 105.04; IR(KBr) 3010(w), 1450(3), 1040(w), 1000(w), 750(3), 720 om'l (s) ; mass spectrum, m/_e_ (rel . intensi- ty) 394(53), 392(100), 390(51), 313(21), 311(20), 311(20); high resolution mass spectrum: calculated m/g for HBr C16 8 2S, 391.86949; found: m/g 391.87042. 52. Treatment of phenanthro[9,10-c]thiophene-1L3-dibromo (148) with NBS Compound 148 (80 mg, 0.2 mmole) was treated with NBS (36 mg, 0.2 mmole) in 20 mL of acetic acid with stirring at room temperature for 20 min. Then water (20 mL) was added and the solution was extracted three times with ether (40 mL) . The organic layer was washed with saturated NaHCO3 solution and water. The combined organic layers were dried over MgSO4 and evaporated under vacuum to give a residue. The residue was chromatographed on silica gel with 20% of benzene in hexane as eluent to. isolate 149 (62%) and 150 (15%). 149; mp 150-152°C; 131112 (250 M82, CDC1)67.90 (m, 3 28), 7.83 (m, 28), 7.76 .(m, 23), 7.73 (m, 28); 13cm: (250 M82, CDC13) 6190.07, 150.84, 134.32, 131.84, 131.85, 129.44, 129.08, 128.44, 126.61, 125.97, 125.50, 125.14, 122.79, 43.69; IR (KBr) 3030(w), 1695(5), 1495(m), 1380(m), 1080 cm-1 (111) ; mass spectrum, m/_e_ (rel . intensity) 109 410(2), 408(3.5), 406(1.8), 329(83), 327(70), 220(100); high resolution mass spectrum: calculated m/g for C6H8Br208, 407.86440; found: m/g 407.86841. 150: mp 160-162°C; 18M8 (250 M82, CDC13) 69.35 (m, 28), 8.71 (m, 28), 7.82 (m, 48); 13cm (62.9 M82, CDC13) 6191.38, 135.46, 133.87, 130.04, 129.22, 127.93, 125.81, 122.99; IR (KBr) 3020(w), 1690(3), 1500(w), 1360 -1 cm (w); mass spectrum, m/g (rel. intensity) 264(76), 236(45), 208(30), 176(100); high resolution mass spectrum: calculated m/g for C16H8028, 264.02450; found: m/e 264.02450 53. Bromination of benzo[1,2-c:3,4-c':5,6-c']trithiophene _3_9_ (a) With one equivalent of NBS Treatment of 3063 (246 mg, l mmole) with NBS (180 mg, l mmole) in 50 mL of acetic acid and workup as decribed gave a mixture which was chromatographed on silica gel with hexane as eluent to yield 153 (10%) and dibromide isomers (30%). 153: mp 110°C (dec.); l8M8 (250 M82, CDC13) 68.57 (d, J=2.7 Hz, 18), 7.67 (d, J=2.7 Hz, 1H), 7.62 (d, J=3.0 Hz, 13), 7.60 (d, 'J=3.0 Hz, 13), 7.58 (s, 13); IR (nujol) 3100(m), 870(m), 855(m), 780(3), 735 cm'1(m); 110 mass spectrum, m/g (rel. intensity) 326 (15), 324(14), 246(34), 80(100). Dibromide isomers: lHMR (250 MHz, CDC13) 68.40 (m, 2H), 7.45 (m, 2H); mass spectrum, _m/g (rel. intensity) 406 (65), 404(100), 402(45), 325(12), 323(10). (b) With four equivalents of NBS Bromination of 30 (80 mg, 0.33 mole) with NBS (240 mg, 1.32 mole) and workup as described above gave tri- bromide isomers 154 and 155 in a 3:1 ratio based on the 1HMR spectral analysis. 1 HMR (250 MHz, CDC13) 68.65 (d, J=2.9 Hz, 13), 8.62 (d, 1H), 8.58 (s, 1B). 155: 68.57 (s, 1H). mass spec- 154 trum of the mixture, m/_e_ (rel. intensity) 486(43), 484 (100), 482(94), 480(32), 405(18), 403(27), 401(13). PART II ATTEMPTED SYNTHESIS OF A NOVEL CYCLOPHANE 111 INTRODUCTION A. REVIEW OF SOME CYCLOPHANES As the structural theory of organic chemistry matured, considerable effort was directed toward strained compounds. Synthetic chemists have constructed internally stressed molecules with a tendency toward molecular collapse. And theoretical chemists are able to predict what extremes of strain might be incorporated into organic structures. Of particular interest among strained molecules are the cyclophanes, in which more than two atoms of an aro- matic ring are incorporated into a larger ring system.]"2 Such molecules provide a good model for the study of molecu- lar strain. For example, the two benzene rings in paracyclo- phanes 1 can be rigidly held face to face by methylene (CH2)m (c H2) n O 1 113 bridges in the para positions. Such molecules offer unusual opportunities to study the behavior of the benzene ring under stress.1 When 11) and n are small, a marked change in the ultraviolet absorption spectrum of 1, as compared to the open chain analogues, is produced by the proximity of the faces of the benzene rings. The strong 17-11 repulsions between the two benzene rings also bend them from planari- ty. The protons on the benzene ring are shifted upfield because of the anisotropy of the ring. Many unusual propert- 1e32'3 have been observed with paracyclophanes and these have been related to the closely held parallel aromatic ring geometries. The cyclophane bridge can be fused to ortho-positions 4 of a‘benzene ring as in 2. The two sp2 carbons of one benzene ring make one of the bridges. The other bridge 5 is made up of methylene groups. In compound 3, both bridges are made of sp2 carbons. Such a system brings the two benzene rings even closer than they are in [2,2] para- cyclophane. Naturally the interaction of the two face-to- face benzene rings is increased. 114 The compounds mentioned so far are closed systems which have two bridges to keep the two benzene rings paral- lel to each other. In compound 3a, the two toluene moieties are also forced to be face-to-face by steric cons- 5 traints. The bonds to the tolyl groups are at a 60° angle. Such a system is an open cyclophane in which the two I @\ 38 H3 H3 toluene groups are able to rotate in a concerted fashion. The NMR spectra of 3 and '3a indicate that structure 3a, with only one bridge, is not markedly different in geometry from 3. There has been considerable recent interest in the properties and structures of 1,8-disubstituted naphthalene derivatives. Such compounds are expected to exist in a state of high steric stress, owing to overcrowding of the substituents which are held in close proximity by approxi- mately parallel bonds to the relatively rigid naphthalene framework. The similar face-to-face arrangement of two benzene rings is also achieved in 1,8-dipheny1naphthalene 4.6 The phenyl rings in this molecule are perpendicular to the plane of the naphthalene ring. This leads to no 1r -orbita1 overlap between the benzene rings and the 115 naphthalene system. The NMR spectrum of 4 shows that the resonance signals at 6 6.85 from the ten protons on the phenyl rings are shifted upfield from the signal for the phenyl protons of 5. The upfield shift is comparable in direction to the difference between the aryl proton signal ' . 4 5 in [2,21paracyclophane (1, m-n=2, ca. 6 6.37) and p-xylene' (67.05) and is of the correct order of magnitude to be accounted for by having each set of phenyl protons shielded by an adjacent parallel benzene ring. Compound 4, like 3a, is an open cyclophane. In 3a, the two benzene rings are. free to rotate. Because of the steric strain in 4, the two benzene rings were initially thought to be incapable of free rotation. Expect- ing a substantial energy barrier to the rotation of the phenyl rings, cis and trans isomers of 1,8-di(meta-substi- tuted phenyl)naphtha1enes, which are illustrated by a top view of the molecule in structures 6a and 6b,7 were expected to be separable. However, NMR spectral data and dipole moment data obtained from certain of these compounds 116 my l) . 1 X 68 ' 6b suggest that equilibration of the two geometrical isomers 6ah-76b is relatively rapid in solution. The energy barrier to rotation is on the order of 10 Kcal/mole and is sufficiently low for the benzene rings to rotate at room temperature. Recent X-ray' diffraction studies of 1,8-di- phenylnaphthalene derivatives have shown that strain causes deformation of the naphthalene ring, a splaying out of the two phenyl rings and a rotation of the phenyl rings so that the nearly parallel planes of the two phenyl rings are at an angle of approximately 700 to the plane of the naphtha- lene ring. The deformation alleviates the nonbonded inter- action between the two phenyls and results in a low rota- tion barrier. The cis and trans isomers of 1,8-dilortho-substituted phenyl)naphthalene were isolated. The rotation barrier of the phenyl rings is 24 Kcal/mole.7b Other closely related open cyclophanes such as 7, 8 and 9 have also been synthesized.°’9 For the peri- tetraphenylnaphthalene 7, overcrowding of the phenyl groups occurs at both the 1,8 and the 4,5 positions. On the 117 contrary, compound 8 does not suffer from any peri-inter- action between the phenyls, because of the longer distance between the phenyl rings. All of the protons of the phenyl 7 rings are at relatively low field ( 67.1-7.9). An x-Ray 10 indicates that the two structure of crystalline 8 phenyl rings are not parallel to one another because of intermolecular interactions present in the crystal. However, compound 8 is believed to adopt a conformation with the two phenyl rings approximately parallel to one another in solution. The phenyl ring at the 9-position of 9 is in a rather special environment, geometrically favorable for interactions with the orbitals of the other two phenyl rings. Closed systems of this type, such as 10a, 10b, 11’12 A characteristic 10c and 11 have been reported. upfield shift of 0.2 ppm occurs in the 1H NMR spectrum on going from the open-chain species 4 to the bracketed 118 11 The shift is attributed to enhancement compound 10a. of the anistropic effect by the forced mutual approach of the phenyl rings. The open and closed cyclophanes mentioned have only two parallel phenyl rings, on opposite sides of the bridges. Cyclophane 12, which possesses two phenyl rings on each side of the bridges, has been synthesized.13 Trans-annular w interactions occur across the two pairs of parallel phenyl rings. One can conceive of using the peri-positions of two naphthalenes or the 1,8-positions of two anthracenes to bridge the p,p' positions of two biphenyls. This would give the novel compounds 13 and 14. These cyclic hydrocar- 2 bons contain only aromatic rings joined by spz-sp carbon-carbon bonds. Molecule 13 possesses four phenyl 119 12 rings and two naphthalene rings with six aryl-aryl carbon bonds connecting them, and 14 has a similar arrangement of rings and closed bonds. Such molecules are in a sense dimers of 4 and 8. The two pairs of parallel phenyl rings in molecule 13 should suffer greater steric strain than those in molecule 14 because of the shorter distance- between them. The dimerization of 4 to 13 should have some impact on the geometry of the molecule 13. It is believed that molecule 13 would have a higher rotational barrier than the monomer 4. The structural features of molecule 14 should not deviate very much from those of the corresponding monomer 8 but 14 would provide the interesting possibility of forming complexes with metal 120 atoms or other molecules in the molecular cavity. Conse- quently 13 and 14 provide worthwhile synthetic targets whose attempted synthesis comprises this part of the thesis. In order to synthesize 13, a. direct and. efficient method is necessary. As mentioned, 13 has six spz-sp2 carbon-carbon bonds connecting‘ the aryl rings. Major methods for making such bonds are outlined below.14 I. II. III. IV. 121 Ullman Reaction141 Cu 2ArI --—-——> Ar-Ar Scholl Reaction14j AlCl3 2ArH > Ar-Ar H+ . . . 14k Radical-mediated Coupling .1. Ar-N2 Ar-N-N-Ar + Ar'H > Ar-Ar' Ar-I, hu . . 141 Benzyne-medlated Coupling Ar-X + > Benzyne (from Ar-X) Ar-Li Ar'-Li V Ar-Ar' Grignard Homo Coupling and Aryl Lithium Homo Couplingl4e catalysts 2AngX > Ar-Ar catalysts 2ArLi > Ar-Ar (catalysts include TlBr, CoBrz, CrC13, CuCl ) 2 122 VI. Lithium Diarylcuprate and Aryl Iodide9 Ar-X + > Alf-Ar. LiAr'Cu VII. Grignard Cross Coupling with Aryl Halidel‘m-h catalysts AngX + Ar'x > Ar-Ar' Each. of these methods has a variety problems associated with it. For example, the Ullman reaction usually requires a high temperature to bring about the coupling reaction. A most serious problem is the limitation of methods I, II and V to the preparation of symmetrical aromatic hydrocarbons. The lack of regiospecificity with respect to both reactants in methods II, III and IV'results in mixtures of isomeric products. Methods VI and VII seem apriori to stand the best chance for success in an approach to 13. This part of the thesis will describe the synthesis of 13. Before describing these results, it will be useful to briefly review previous synthetic routes to 1,8-diary1- naphthalenes. 123 3. REVIEW OF THE SYNTHESIS OF 1,8-DIPHENYLNAP3THALENE The first synthesis of 1,8-diphenylnaphthalene is 6 summarized in Scheme I. Michael addition of phenylmag- nesium bromide to 15 gave 16 which was brominated to Scheme I ————-> ————-> 15 15 17 ' DDQ HBr 0. PhL) 1 HOAc 18 19 - 4 27% yield the bromide 17. Dehydrohalogenation of 17 gave the thermodynamically controlled product 18. Addition of phenyllithium to ketone 18 gave 19, which was dehydrat- ed and dehydrogenated with DDQ in boiling benzene to yield 1,8-dipheny1naphthalene 4. Similar approach15 to the synthesis of 4 reported by A.S. Bailey, et a1., is summarized in Scheme II. The strategy was to construct an alicyclic intermediate with 124 Scheme II Ph 0 Ph 0 Ph H2 \ _ 0 Ph 0 ' Ph 0 H PhLi ___,..=. no ——-».: ---> Hs SH 3 \_.l O. P“ ———-éD' -—-——-—)> the necessary carbon skeleton. Aromatization was then ac— complished by a combination of dehydration and/or dehydro- genation steps. This strategy has been used to synthesize substituted 1,8-diphenylnaphthalenes.16 For example, 1,8-bis(3'- chlorophenyl)naphtha1ene 20 was prepared as shown in Scheme III. However, the route suffers from having too many steps. In addition, House found that the dehydrogenation of 21 led not only to the desired product but also to a 17 rearrangement product. The isomeric' hydrocarbon 22 was isolated in comparable yield to 4. 125 Scheme III 0. C1 F1 <—- .0 .._ 0‘ 32% A 20 4 2'2 54% 46% In 1972, a more direct synthetic route to 4 was re- ported.18 Although the Ullman coupling reaction of 23 did not provide a useful. route to 4, coupling of the diiodide 23 with lithium diphenylcuprate was more 126 effective. The highest overall yields of 4 were obtained from the diiodide 23 by a two-stage process in which the intermediate monophenyl iodide 24 was isolated and then treated with excess diphenylcuprate. However, the reaction proved capricious when equimolar amounts of the cuprate and the iodide 24 were used; an unusually high percentage (18%) of the symertrical coupling product 25 was pro- duced. This suggests that formation of the symmetrical cuprate intermediate 25a may be favored by a special type of stabilization involving coordination of the metal with the adjacent phenyl rings. Transition-metal compounds of copper, iron, silver, rhodium, palladium and nickel have been known to catalyze the coupling reaction between Grignard reagents and orgnic 14 halides. Particularly, nickel and palladium compounds 127 Ph Ph 4 Ph .@ 25 are often used as catalysts. ,The mechanism proposed19 is shown in Scheme IV. A catalyst 26 reacts with a Grignard reagent to form the intermediate diorganometal complex 27 which is subse- quently converted to the complex 28 by an organic halide. Reaction of 28 with Grignard reagent then forms a new diorgano complex 29 from which the cross-coupling product is released by the attack of the organic halide, possibly via penta-coordinated intermediate 30, thereby regenerat- ing the original complex 28 to complete the catalytic cycle. 128 Scheme IV MX2 26 2'3ng In 1976, nickel catalysts were applied to the synthe- sis of 1,8‘--dipheny1naphthalene.14a A catalytic amount of a soluble organo-nickel complex is employed to effect the aryl Grignard-aryl halide coupling in high yield under very mild conditions. This provided a direct route to 1,8-di- phenylnaphthalenes. Both nickel(II) acetylacetonate [Ni (acac)2] and‘ dichloro-l,2-bis(diphenylphosphino)ethane nickel(II) were highly active in bringing about heteroaryl coupling. The complexes were equally effective. Reactions were found to proceed smoothly with a molar ratio of nickel catalyst:aryl halide of 1:100. Use of a 7:1 Grignard:di- iodonaphthalene ratio was necessary to give a good result. 129 Incomplete conversion occurred when only a 3:1 Grignard:di- iodonaphthalene ratio was used. The reaction was carried out at ~15°C to -10°C. Use of higher temperatures decreased the yields. The relative reactivity of aryl halides in this system toward nickel complex-catalyzed coupling with a Grignard reagent was found to be I>Br>>C1. Interestingly, the Grignard reagents of iodobenzene and bromobenzene were found to give pronounced differences in the coupling reaction. Use of phenylmagnesium bromide instead of the corresponding iodide decreased the yield of 4 by more than half. Possible strategies for the synthesis of 13, the dimer of 1,8-diphenylnaphthalene, are shown in Scheme V, based on the coupling method VII. There are three routes. Route a is the most direct. Route b, in which the molecule is broken symmetrically, is a homocoupling re- action of molecule 31 which can be prepared by cross- coupling of 32 with 33 or 34 with 35. The halide X' should be more reactive than the halide X so that in the presence of a catalyst the Grignard reagent can selectively replace the more reactive halide. Route c is a crosscoup- ling reaction between 36 and a 1,8—dihalonaphthalene. In order to synthesize 36, another cross coupling between 34 and 37 or between 32 and 38 must be carried out. RESULTS AND DISCUSSION 1. Synthesis of l-Phenylnaphthalene 5 as a model system l-Phenylnaphtnalene 5, a known compound, served as a model system for practicing strategies. Route 3 involves the cross coupling of phenylmagnesium bromide with 1-naph- thyl iodide, whereas Route b involves the same type of reaction between l-naphthylmagnesium bromide and iodo- benzene, each coupling being carried out in the presence of Ni(acac) . Both routes proved capable of preparing 5 in 2 good yield. .r + W' Ni(acac)2+ O O - + 100%1 MgBr l 131 132 2. First Attempt to synthesize 13 Treatment of 1,4-diiodobenzene with excess naphthyl- magnesium bromide in the presence of catalytic amounts of Ni(acac)2 at room temperature led to the biscoupling pro- duct 39 in 31% yield. In such a system, without any steric hindrance, the coupling reaction could be carried out smoothly. 4’ Ni (acac)2 133 di-Grignard reagent 40 and 4,4'-diiodobipheny1. However, the di-Grignard reagent 40 could not be prepared from 1,8-diiodonaphtha1ene and magnesium. Quenching the Grignard solution with methanol gave only starting material and l- iodonaphthalene. This} type of reaction of Route a in Scheme V perhaps will result in many products, so there was no special effort to make the di-Grignard reagent from 1,8- diiodonaphthalene and active magnesium powder. 3. Synthesis of 1—(4'-Chloropheny1)naphthalene (41) and 1,8-(di-4'-Chlorophenyl)naphthalene (42) The 1—(substituted phenyl)naphthalene system is used Cl‘ . o oo a» OS 41 0| Cl C1 CI 00 N i(acac)2 21% 41% 134 as a model system for the synthesis of 31 via 32 and 33. The successful cross coupling reaction between 1- iodonaphthalene and 4-chlorophenylmagnesium bromide en- couraged us to carry out the same reaction on 1,8-diiodo— naphthalene. The product 42 was obtained in a 21% yield. Besides the desired product 42, side product 41 was isolated. It arises from an exchange reaction between the intermediate 43 and the Grignard reagent. After workup, 44 was quenched by methanol to give 41. Cl ’ Cl MgBr ’ O O MeOH+.O Niexxnjz 43 44 41 4. Synthesis of 1,8-813(4'-bromophenyl)napththalene (45) and 1-(4'-Bromophenyl)naphthalene (46) Usually aryl chlorides are not as reactive as aryl bromides or iodides in Grignard-aryl halide coupling re- actions. So the same route to prepare 42 was used to prepare 1,8-bis(4'-bromopheny1)naphthalene 45. Although 135 the product 45 was formed, it was in poor yield (7%). ; r Br Br © 4408;, Ni(acac12 O 45 ‘1' DOlymer The poor _ yield might be attributed to the steric hinderance in such a system. However, when the same reac- tion was applied to the model system, the product 46 was Br 8' O O MQBF * + polymer 0 Ni(acac)2 a O 46 13% also isolated in low yield. In these two reactions, a poly- meric substance was obtained, so the para position of the Grignard reagent is sensitive to itself in the presence of the catalyst. 136 5. Synthesis of l-(4'-Bromophenyl)naphthalene 46 and Its Homocoupling Reaction Initially 4-bromophenylmagnesium. bromide was thought to attack only the more reactive 1,8-diiodonaphthalene, in the presence of nickel catalyst. However, some undissolv- able polymer was found. Thus, the coupling reaction was not entirely selective, since the Grignard reagent presumably also displaced its own 4-bromo substituent, resulting in a polymer. Therefore the para-position of the phenyl Grignard reagent should be protected and later removed by bromide or iodide. The trimethylsilyl group seemed the best choice, because it is inert to Grignard reagents and ”can easily be replaced by electrophiles. For example, in the first of the following reactions, the trimethylsilyl group can be rapid- ly removed by bromine, which serves as an electro- phile.20 In the second example, bromine selectively \si/ 0 —'———» o 00 Emmi 137 removes the two protecting groups at the 2- and 6-posi- tions in the first step.21 Scheme VI j “9 + \'- This modified process was then applied to the syn- thesis of model compound 50, as shown in Scheme VI. 138 4-Trimethysilylphenyl iodide 47 was prepared in 70% yield from 1,4—diiodobenzene with one molar equivalent of n-BuLi to form the monolithic derivative which was trapped by excess trimethylsilyl chloride. The Grignard reagent 4721 made from 47 and magnesium was added to a solution of l-iodonaphthalene and Ni(acac) in THF. Compound 48 was 2 isolated after workup by column chromatography. The protect- ing group of 48 could be easily removed by bromine to afford 46. Treatment of 46 with n-BuLi and cupric chlo- ride gave the dimer 50 in 30% yield. 3 The 13CMR spectrum of 50 contained fourteen aro- matic carbon peaks as expected. The mass spectrum of 50 showed the molecular ion (M+ a 406) of 50. 6. Synthesis of l,8-Bis(4'-halophenyl)naphthalenes 4S and 55 The Grignard reagent of 47 was added to a solution of 1,8-diiodonaphthalene with Ni(acac)2 as the catalyst. In addition to the desired 51, 48 was obtained as the major product. The low yield of 51 is due to the exchange reaction of the Grignard reagent with 49 which increased the yield of 48. The l3CMR spectrum of 51 had ten aromatic carbon peaks and one alkyl carbon peak as expected. There were four upfield shifted protons which'should be due to the protons on the phenyl rings because of the 1r interaction 139 l/ \I,’ \Si SI \' / l. \SI/ 0 .0 N322: 0 O * O O 51 48 13% 70% ¢ -s'i- A 49 between them. It is known in the literature that Grignard reagents undergo an exchange reaction22'14a with aryl halides during cross coupling reactions. For example, the amount of biphenyl, the side product which arises during the coupling reaction of phenylmagnesium iodide with 4-iodoanisole is formed by the exchange reaction of Grignard and aryl halide, and is isolated in about 16% to 25% yield.22 Particularly when steric hindrance is present, as in 1,8- diphenylnaphthalene 4, the side product 5 is formed in comparable amount by using phenylmagnesium bromide. Steric 140 Mgl 30 © MN: 4+ hindrance probably accelerates the exchange reaction be- 14a 71% 16-25% tween the Grignard reagent and the aryl iodide. PhMgBr é.“ PhMgBr Ni(acac)2. ; PhMg Br Ph Mg Br 7. Synthesis of l,8-Bis(4'-halophenyl)naphthalenes 45 and 55 with Arylzinc Chloride Solution Recently arylzinc chlorides have been used instead of the corresponding Grignard reagents for coupling reactions 141 . with aryl halides in the presence of Ni(P33)4 as the catalyst. The formation of side product due to the exchange reaction between the Grignard reagent and aryl halide is decreased. For example, the amount of biphenyl formed as a 22 by-product is reported to be only 3% in the following coupling reaction: N 39 © This modified cross coupling method was used to pre- pare Sl. Trimethylsilylphenyl iodide was treated with one \Sli, \‘i’ \Si’ —-»v —2—»m 3 Li 53 ZnCl s4 \S©i’ 142 molar equivalent of lithium metal to prepare trimethyl- silylphenyl lithium 53 which then displaced the chloride on zinc chloride to form 54. The solution of 54 was added to a THF solution of 1,8-diiodonaphthalene and Ni(P 33)4 at room .temperature. Compound 51 was formed as a major product in 40% yield. Treatment of 51 with two molar equivalents of iodine lHMR spectrum of monochloride gave the desired 55 . The 55 indicated that four protons on the phenyl rings were shifted to upfield ( 5 6.95, d, J=8.5 Hz)‘. The other four protons of the phenyl rings appeared at 67.26 (d, J=8.5 Br Br 143 Hz). There were three double doublets at 5 7.91, 7.50, and 7.31 which were due to the protons on the naphthalene ring. The upfield shift of the four protons on phenyl rings is because of the u interaction between the benzene rings. When treated with two molar equivalents of bromine, compound 51 gave dibromide 45. When compound 55 was treated with magnesium, the starting material was recovered completely. However, if ethylene dibromide was added as an entrainer to activate the magnesium surface, the di-Grig- nard reagent formed and could be quenched with methanol to give 1,8-diphenylnaphthalene 4 quantitatively. 8. Attempts to synthesize 13 (a) Coupling Reactions with 57 and 55 with Nickel Com- pounds as Catalysts The last step to 13 is a homocoupling reaction of 55. The two 4'-positions on the phenyl rings of 55 must be connected to the same positions of another molecule to prepare 13. Although this is a homocoupling reaction, which is usually easier than a cross coupling reaction, the reaction is not favorable for entropy reasons. In addition, the two phenyl rings are not exactly parallel to each other. This is a most serious problem, but the efficiency of nickel compounds for coupling reactions opens a chance to synthesize 13. 144 Since the last step is nota cross coupling reaction, the exchange reaction between the Grignard reagent and the aryl halide should not influence the reaction. A solution of di-Grignard reagent 57 was used directly without ex- change with zinc chloride. A solution of 57 was added to a solution of THF containing 55 and Ni(acac)2. The reac- tion was followed by TLC. At room temperature, no reaction occurred. Therefore the mixture was heated at reflux over- night. After workup, the residue was chromatographed on silica gel. The starting material 55 and quenched com- pound 4 were isolated in 80% yield. Additionally, the 'dimer' 58 with only one side connected was isolated in .I. I I H H ©© oo —5’-—>OQ+oo+ Ni(acac)2 55 4 ©© 58 15% yield. The eluent of the other fractions was evaporated under vacuum to give a residue. The residue was rinsed with ether and filtered to give a white solid which showed a 145 molecular ion peak at ‘m/g_ 556 for 13 ~on mass spectro- metry. The base peak ‘was at {m/g_ 278, which corresponds to the fragmentation of 13 to its half molecule. The substance was isolated in less than 3 mg. An attempt to obtain the 1H NMR spectrum of this substance failed. Since compound 58 possesses a C2 axis, the 13CMR spectrum showed twenty-two aromatic carbon peaks. In the mass spectrum, the molecular ion (M+ = 558) was shown. The base peak was at m/g 279. The main reason for the low yield of 13 can be attri- buted. to the geometry' of. the intermediates 56a. and 56b which possibly possesses the arrangement of phenyl rings analogous to those in structure 4, with the phenyl rings splayed in and out of the plane of the naphthalene ring. 563 56b 146 Ni(P33)2Cl2 was used as a catalyst, to 'try to improve the yield. However, the reaction gave the same result. Other nickel compound, Ni(dppp)2, was also used, but lead to no formation of 13. (b) Coupling Reaction of 55 with n-BuLi and CuC1223 It has been mentioned that the model molecule 46 gives the dimer 50 after treatment of 46 with n-BuLi and CuClz. This type of reaction is a modification of the Ullman reaction. Hopefully this method could be applied to the dimeriza- tion of 55. Therefore compound 55 was treated with 2.2 molar equivalents of n-BuLi and quenched with trimethyl- silyl chloride to give 51 (90%). This showed that the dilithio compound 59 was formed. l | \Si/ \si / \. 55 CUC|2 '——-> 4 + 58 50% 16% 147 To a solution of the dilithio compound 59 was added two molar equivalents of cupric chloride. Workup resulted only in the isolation of 4 (50%) and 58 (16%). (c) Coupling Reaction with Di-Grignard Reagent 57 and Cuprous Bromide 24 there is an example of the syn- In the literature thesis of a compound which is very similar to the system of 13, using a Grignard reagent and cuprous bromide in a homocoupling reaction. Along with compounds 62 and 63, dimer 61 was isolated as a minor product. 61 52 6‘3 63% L496 45% 148 Cuprous bromide was added to the solution of Grignard reagent 57. Workup as described in the literature gave only 58 (8.8%) and 4 (90%). Other salts such as RhCl3 and CuBr2 were used and led to no isolation of 13. lwgl hMfl CuBr .0 57 (d) Coupling Reaction between 55 and Ni(P33)325 Aryl halides are able to undergo homocoupling reac- tions in the presence of Ni(P 33)3 as the catalyst without the formation of the corresponding Grignard rea- gent. Even ortho substituted aryl halides can be coupled in good yield.25b This new procedure might be of value in the dimeriza- tion of 55. Therefore compound 55 was added to a solution of DMF and Ni(P¢3)3, which was prepared from 25b Ni (P ¢3)2C12, P453 and zinc . After workup, only the starting material was recovered. 149 (e) Coupling Reaction of 57 with l,4-Dichloro—2- Butyne as an Initiator26 Recently, a new method for aryl coupling using 1,4- dichloro-Z-butene and l,4-dichloro-2-butyne as the organic 26 This method was coupling promotor has been developed. applied to the coupling of 57.- However, the desired pro- duct 13 was not found. cum—5020014201 4>4+ 58 80% 5.4 % 150 9. Another Approach The third strategy, in which the last step is a cross coupling reaction of 64 and 1,8-diiodonaphthalene, is shown in Scheme VII. Connections between naphthalenes and biphenyls are the bonds which must be formed in the two cross coupling reactions. Scheme VII Lflflg_ 2.Ni°& 151 The synthesis of 66 is shown in Scheme VIII. 4,4'- Dibromobiphenyl was treated with one molar equivalent of n-BuLi and then excess trimethylsilyl chloride to prepare 67. Organozinc chloride 65 was obtained by a displace- ment reaction between zinc dichloride and the Grignard Scheme VIII 1 \Si’ ‘3? \Si/ Mg. ’ ZnC'z —> —> .0 Br MQB" ZnCl 67 68 65 \gi’ I ( \l“,' SI .. 3 152 reagnet 68, which in turn was prepared from 67 and magnesium. The solution containing 65 was added to a solu- tion of 1,8-diiodonaphthalene and Ni(P 33)4 in THF. After workup, the products were chromatographed on silica gel with hexane as eluent. Compound 66 was isolated as a minor product. Compound 69 was formed as the major product. This result is attributed to the more steric hindrance in 66 than in 51 which increases the yield of side product 69 and decreases the yield of desired pro- duct 66. The yield of 66 was too low' to continue the scheme. EXPERIMENTAL l. l-Phenylnaphthalene (5) (a) From iodobenzene and l-naphthylmagnesium bromide Magnesium turnings (0.309, 12 mole) were placed in a three-necked round-bottomed flask equipped with ' a reflux condenser, and the system was flushed with argon while the flask and metal turnings were heated with a heat gun. Approximately 10% of a solution of l-bromonaphthalene (2.07 g, 10 mole) in 20 mL of ether was added from an addition funnel. The mixture was heated to initiate the reaction. The remaining l-bromonaphthalene solution was added just rapidly enough to maintain a gentle reflux (about 15 min). The solution was refluxed for another 45 min and transfer- ed to an addition funnel. The Grignard solution was added slowly (during 1 h) to a solution of 2.04 g (10 mole) of iodobenzene and 26 mg (0.1 mole) of nickel(II) acetyl- acetonate27a in 15 mL of ether at -20°C. The mixture was stirred for an additional 5 h at this temperature and then left stirring overnight at room temperature. The mix- ture was quenched with concentrated NH4C1 solution and 153 154 the aqueous solution was extracted with ether. The combined organic layers were dried over M9804. The solvent was evaporated. Compound 56 was obtained as a colorless oil in quantitive yield. lHMR(CDC13) 68.0-7.2 (m); mass spectrum, m/g (rel. intensity) 204(100), 127(75). (b) From l-iodonaphthalene and phenylmagnesium bromide Phenylmagnesium bromide (12 mole) was prepared from bromobenzene (1.9 g, 12 mole) and Mg (0.30 g, 12 mole) in 20 mL of ether by the method described above. The Grignard solution was added to a solution of l-iodonaphthalene (2.54 g, 10 mole) and 26 mg (0.1 mole) of Ni(acac)2 in 20 mL of ether at -20°C. The solution was kept at —20°C for 5 h and left stirring overnight. Workup as described above gave a quantitative yield of 5 as an oil. 2. l,4-Bis(l'-naphthyl)benzene (39) l,4-Bis(l'-naphthyl)benzene was prepared by the same procedure as described in the synthesis of 5. From 1.65 g (5 mole) of 1,4-diiodobenzene and 11 mole of l-naphthyl- magnesium bromide in the presence of Ni(acac)2 (13 mg, 0.05 mole), compound 39 (0.51 mole, 31%) was isolated, following column chromatography on silica gel with hexane as eluent. The product could be recrystallized from hexane, 1 mp 19s-197°c. HMR (60 MHz, c0c13> 68.0-7.18 (m); 155 l3CMR (20 MHz, cnc13) 5140.03, 139.77, 133.97, 131.74, 129.98, 128.36, 127.74, 127.05, 126.11, 125.84, 125.44; IR(CC14) 3050(m), 1450(m), 725 cm-1(s); mass spectrum, m/g (rel. intensity) 330(100), 202(30), 163 (27); high resolution mass spectrum: calculated m/g for C26318’ 330.14085; found: m/g 330.14070. 3. Attempt to prepare the di-Grignard reagent from 1,8- diiodonaphthalene and magnesium. Magnesium turnings (120 mg, 5 mole) were placed in a three-necked round-bottomed flask equipped with a conden- ser. The system was flushed with argon while the flask and magnesium turnings were heated with a heat gun. 1,8-Diiodo- 14a in 20 mL of dried THF was naphthalene (1.9 g, 5 mole) added to the flask through an addition funnel. The mixture was heated to reflux to initiate the reaction. Heat was required during addition of the 1,8-diiodonaphthalene solution. The mixture was refluxed overnight in an oil bath and then was quenched with saturated NH 4Cl solution. The mixture was extracted with ether and the organic layer was dried over M9804. Evaporation of the solvent gave a resi- due which was chromatographed on silica gel with hexane as eluent to give l-iodonaphthalene (38%) and recovered start- ing material (50%). 156 4. l-(4'-Chlorophenyl)naphthalene (41) p-Chlorophenylmagnesium iodide (15 mole) prepared from p-chloroiodobenzene (3.6 g, 15 mole) and magnesium turnings (0.40 g, 17 mole) in 20 mL of ether was added to a stirred solution of l-iodonaphthalene (1.52 g, 6 mole) and Ni(acac)2 (25 mg, 0.1 mmole) in 20 mL of ether at -20°C under argon over 1.5 h. The mixture was held at -20°C for 3 h. Hydrolysis with saturated NH4C1 solution and water followed by drying over 149804 and evaporation of the solvent gave a residue. The residue was chromato- graphed on silica gel with hexane as eluent to recover 0.6 g (40%) of 1-iodonaphthalene and 0.70 g (49%) of 41.28 1mm (60 MHz, c0013) 67.78-7.00 (m); 13cm: (20 MHz, CDCl > 5139.15, 138.88, 133.79, 133.29, 131.43, 131.29. 3 128.56, 128.4l,-128.33, 127.95, 126.87, 126.20, 125.62, 125.29; mass spectrum, m/g (rel. intensity) 240(27), 238(86), 202 (100). 5. 1,8-Bis(4‘-Chlorophenyl)naphthalene (42) The same procedure for synthesizing 41 was applied to prepare compound 42. Addition of 15 mole of p-chloro- phenylmagnesium iodide to a solution of 1,8-diiodonaphtha- lene (1.14 g, 3 mole) and Ni(acac) (20 mg) in 20 mL of 2 ether at -20°C during a 2 h period, followed by addition- al 2.5 h at -20°C, afforded, after column chromatography 157 on silica gel with hexane as eluent, 225 mg (21%) of 42, mp 185-187°C, which was recrystallized from hexane. In addition, 41% of 41 was also isolated as a side product. For 42: 1mm (20 MHz, CDCl) 67.80-7.17 (m, 103), 3 6.77 (m, 481; 13CMR (20 MHz, cuc13> 6141.44, 138.95, 132.21, 131.08, 130.89, 129.04, 128.35, 127.36, 126.84, 125.23; IR(CC14) 3050(m), 1500(8), 1400(m), 1100(3), 725 cm-1 ( 3); mass spectrum, m/g (rel . intensity) 352 (1.6), 350(49), 348(76), 316(15), 314(100), 276(78). 6. 1,8-Bis(4'-bromophenyl)naphthalene (45) p-Bromophenylmagnesium bromide (15 mole) was prepared from 3.6 g (15 mole) of p-dibromobenzene and 380 mg (15 mole) of magnesium turnings in 30 mL of ether. The Grig- nard solution was added to a solution of 1,8-diiodonaphth- alene (1.1 g, 3 mole) and Ni(acac)2 (20 mg) in 15 mL of ether at -20°C. Workup by the same procedure described for the preparation of 41 gave some polymeric substance which was separated from the organic solution by filtra- tion. The filtrate was evaporated under vacuum and chromato- graphed on silica gel with hexane as eluent to isolate a trace of 45 (91 mg, 7%), mp 209-21o°c. lama (60 MHz, CDC13) 57.91-7.22 (m, 6H), 7.0 (d, J=8 Hz, 4H), 6.63(d, J=8 Hz, 4H); 13CMR (20 MHz, cnc13> 6141.86, 138.93, 131.44, 130.81, 130.37, 129.10, 127.49, 127.35, 127.07, 125.25; IR (KBr) 3010(w), 1590(w), 1490(8), 1360(3), 158 1180(m), 1080(m), 1010(8), 880(m), 810(8), 770(8), 710(W), 690 cm-1 (w); mass spectrum, m/g (rel. intensity) 440 (24), 438(48), 436(36), 357(2), 359(2), 278(60), 277(44), 276(46); high resolution mass spectrum: calculated m/g for C22H14Br2, 435.94633; found: m/g 435.94544. 7. 1-(4'-Bromophenyl)naphtha1ene (46) By the same procedure used to prepare 45, a polymer- like substance and a low yield of 46 were obtained from p-bromophenylmagnesium bromide (8 mole) and 1-iodonaphth- alene (760 mg, 3 mole) in the presence of Ni(acac)2 (10 mg). Compound 46 (87 mg, 13%) was separated on silica gel with hexane as eluent. 1HMR (60 MHz, CDCl ) 67.80-7.0 3 (m); 13cm (20 MHz, c0013) 6138.96, 133.87, 131.69, 131.44, 128.75, 128.36, 128.14, 128.03, 127.20, 126.86, 126.25, 125.91, 125.68, 125.33; IR (CC14) 3050(8), 1600 (s), 1500(s), 1410(m), 800 cm71(s); mass spectrum, m/g (rel. intensity) 284(8), 282(8); 202(100); high resolution mass spectrum: calculated m/g for C16fillBr' 282.00447; found: m/g 282.00714. 8. l-(4'-Trimethylsi1ylpheny1)naphthalene (48) p-Trimethylsi1ylpheny1maganesium iodide (11 mole) was prepared from 3.0 g (11 mole) of 4-trimethylsilyliodo- benzene and 0.30 g (13 mole) of magnesium turnings in 25 159 mL of ether. Addition of the Grignard solution to a 2.54 g (10 mmole) solution of l-iodonapththalene and Ni(acac)2 (20 mg) in 30 mL of THF at -20°C over 2 h, followed by stirring at -20°C for another 3 h gave, after column chromatography on silica gel with hexane as eluent, 1.0 g (36%) of 48. 1mm (60 MHz, 0001 ) 67.75-7.00 (m, 3 11H), 0.30 (s, 9H), 13CMR (20 MHz, c0c13> 5142.21, 141.29, 140.11, 134.86, 134.26, 132.64, 130.44, 129.24, 128.61, 127.89, 127.08, 126.97, 126.73, 126.35, 1.02; IR (CC14) 3050(m), 2950(8), 1400(w), 1250(w), 800 CIR-1(8); mass spectrum, _m/g (rel. intensity) 276(39), 261(100); high resolution mass spectrum: calculated mfg for C19H208i, 276.13343; found: _m/g 276.13528. 9. 1-(4'-Bromophenyl)naphthalene (46) from the electro- philic bromination of 48 To a solution of 552 mg (2 mole) of 48 in 10 mL of carbon tetrachloride was added 320 mg (2 mole) of bromine in 5 mL of CCl at room temperature. The solution was 4 stirred overnight and then washed with saturated NaHSO3 solution and water. After drying over MgSO4, the solvent was removed under vacuum. The residue was chromatographed on silica gel with hexane as eluent to give an oil (380 mg, 67%) of 46. The lHMR and IR were identical with those of the previously prepared sample. 160 10. Dimerization of l-(4'-bromopheny1)naphthalene (46) To a solution of dry THF (20 mL) containing 46 (280 mg, 1 mole) was added n-BuLi (2.0 M, 0.6 mL) at -78°c under argon. The solution was stirred at -78°C for 30 min and then cupric chloride (140 mg, 1 mole) was added to this solution at -78°C. The mixture was kept at -78°C for 2 h and warmed up to room temperature with stirring overnight. Ether (100 mL) was added. The mixture was washed with 4 M HCl solution and water. Evaporation of the solvent gave a residue which was chromatographed on silica gel with hexane as eluent to give 120 mg (30 %) of 4,4'-bis(a—naphth- yl)bipheny1 50, mp zoo-201°C 1m (60 MHz, cum) 3 57.95-7.20 (m); 13cm (20 MHz, cnc13> 6139.91, 139.78, 133.92, 131.68, 130.61, 128.35, 127.76, 127.51, 127.43, 126.99, 126.63, 126.09, 125.83, 125.44; IR (KBr) 3030(m), 1500(m), 1400mm, 840(m), 830(m), 800(8), 760cm-1(s); mass spectrum, m/g (rel. intensity) 406 (10.6), 202 (64), 139(100); high resolution mass spectrum: calculated m/g for C 406.17216; found: m/g 406.17412. 32522' 11. l,8-Bis(4'-trimethylsily1pheny1)naphthalene (51) 1 , 8-Bis ( 4 ' -tr imethylsi lylphenyl ) naphthalene (175 mg , 13%) was separated by chromatography on silica gel with hexane as eluent from the reaction between p-trimethylsilyl- phenylmagnesium iodide (17 mole) and 1,8-diiodonaphthalene 161 (1.1 g, 3 mole) in the presence of Ni(acac)2 (50 mg) by the same procedure used to prepare 48. For compound 51: 1 mp 113-115°C; HMR (60 MHz, cnc13) 67.70-7.20 (m, 10 H), 6.72 (br, 48), 0.30 (s, 18H); 13CMR (20 .MHz, c0013) 6144.71, 141.69, 138.13, 136.55, 133.09, 132.10, 130.35, 130.12, 129.33, 126.15, 0.99; IR (CC14) 3080(m), 2960(8), 1450 (m) , 1250(8), 800 cm-1(s); mass spectrum, m/g (rel. intensity) 424(100) 409(55); high resolution mass spectrum: calculated m/g for C28H32Si2, 424.20426; found: m/_e_ 424.20'727. In addition to 51, compound 48 was isolated in 70% yield. The NMR and IR spectra were identical with those of a previously prepared sample. 12. 1,8-Bis(4'-trimethylsilylpheny1)naphthalene (51) from the arylzinc chloride A solution of 10 mmole of p-trimethylsilylphenyl- lithium was prepared from 2.76 g (10 mole) of p-trimethyl- silyliodobenzene and excess of (lithium metal in 20 mL of ether by the same procedure used to prepare the Grignard reagent. The solution was added to a solution of ZnC12 (1.4 g, 10 mole) in 15 mL of THF and stirred for 1 h. This zinc chloride solution was added to a solution of 1,8-di- iodonaphthalene (1.1 g, 3 mole) in 20 mL of dry THF with Ni(Pds)4 (0.30 mole) as the catalyst over 2 h at room temperature. The solution was stirred overnight and 162 quenched with saturated NH 4C1 solution. The mixture was extracted with ether and the organic layer was dried over MgSO4. Evaporation of the solvent gave a residue which was submitted to chromatography (silica gel) with hexane as eluent to separate 500 mg (40%) of 51. The product could be recrystallized from hexane and ethyl acetate, mp 113- 115°C. 13. 1,8-Bis(4'-bromopheny1)naphtha1ene (45) from compound 51 and bromine To a solution of 51 (220 mg, 0.5 mmole) in 10 mL of CC14 was added a solution of' CC14 (5 mL) containing 160 mg (1 mole) of bromine at room temperature. The solution was stirred overnight and washed with saturated sodium bisulfite solution and water. Removal of the solvent under vacuum gave a residue which was recrystallized from hexane and ethyl acetate to afford 110 mg (50%) of 45, mp 210- 212°C. The lHMR and 'IR spectra were identical with those of the previously prepared compound. 14. 1,8-Bi8(4'-iodopheny1)naphthalene (55) 29 Iodine monochloride (200 mg, 1.2 mmole) in 5 mL of CC1 was added to 258 mg (0.6 mole) of 51 in 10 ml. of 4 CC1 The solution was stirred overnight and washed with 4. 163 saturated sodium thiosulfate solution and water. The sol- vent was removed under vacuum to give a yellow solid which was recrystallized from hexane and ethyl acetate to yield 166 mg (52%) of 55, mp 224-225°c. 1mm (250 MHz, CDC13) 57.91 (dd, J1=8 Hz, J J1=8.0 Hz, J 2=l.2 Hz, 23), 7.50 (dd, 221.2 Hz, 2H), 7.31 (m, 2H), 7.26 (d, J=8.5 Hz, 4H), 6.59 (d, J=8.5 Hz, 4H); 13cm (20 MHz, @013) 6142.44, 139.01, 136.41, 135.36, 131.74, 130.76, 129.09, 125.25; IR (KBr) 3010(w), 1590(w), 1580(8), 1390(8), 1360 (w), 1170(w), 1000(8), 880(m), 810(8), 770(8), 710(w), 690 cm-l(w); mass spectrum, _m/g (rel. intensity) 532(17), 405(1), 278(32), 277(35), 276(44), 139(100); high resolu- tion mass spectrum: calculated m/g for C22H14I2, 531.91887; found: m/g 531.91586. 15. The Di-Grignard Reagent of 55 A solution of ethylene dibromide (570 mg, 3 mole) in 10 ml. of THF was added dropwise to a refluxing THF (10 mL) solution containing 55 (532 mg, 1 mole) and magnesium turnings (120 mg, 5 mole). The solution was heated at reflux until all of the magnesium turnings had disappeared. Menthanol (2 mL) was added. The solution was extracted with ether (100 mL) and washed with water. The solvent was remov- ed under vacuum to give a residue which was recrystallized from hexane to gave 280 mg (100%) of 4, mp 145-147°C (111:.14a 147-148°C). 164 16. Attempt to synthesize 13 from the di-Grignard rea- gent 57 (a) With Ni(acac)2 as catalyst To a solution of 55 (532 mg, l mmole) and Ni(acac)2 (10 mg) in 10 mL of THF was added 1 mole of 57 in 20 mL of THF at room temperature under argon. The reaction was followed by TLC. No reaction occurred at room temperature. The mixture was then heated at reflux overnight. Ether (30 mL) was added and the mixture was washed with NH 4Cl solu- tion. Removal of the solvent under vacuum gave a residue which was chromatographed on silica. gel with. hexane as eluent to recover 55 (420 mg, 80%) and 4 (224 mg, 80%). Additionally , compound 4 , 4 ' -bis( a-phenylnaphthy1)biphenyl 58 was isolated in 15: yield, mp 180-181°c. lHMR (250 MHz, CDC13) 68.00-6.75 (m); J“BCMR (20 MHz, CDC13) 6140.40, 140.11, 139.72, 139.43, 137.26, 136.36, 136.19, 135.56, 132.22, 131.94, 130.98, 130.19, 129.37, 129.08, 128.78, 127.68, 127.21, 127.01, _126.51, 126.25, 125.91, 125.25; IR (KBr) 3010(s), 1580(3), 1380 cm‘lts); mass spectrum, m/g (rel. intensity) 558(51), 279(100). Evaporation of the eluent in the fractions collected tubes after 58 gave a white solid (2 mg) which was washed with ether. Mass spectrum, m/_e_ (rel. intensity) 556 (65), 278(100), 202(49), consistent with structure 13. 165 (b) With Ni(pp3_)_291_§7b as catalyst By the same procedure described above except using Ni(Pttt3)2Cl2 (20 mg) as the catalyst, 4 (80%), 55 (80%), and 58 (11%) were isolated. A trace (1 mg) of the substance whose mass spectrum showed the molecule ion of 13 was also isolated. (c) With bis(1,3-dipheny1phosphino)propanenickel(II) as catalyst 27b (11 mg) as the catalyst for the Using Ni (dppp ) 2 coupling reaction between 55 (532 mg, 1 mole) and 57 (1 mole) did not give the substance which showed the molecular ion of 13. Only compound 58 was isolated, in 12% yield. (d) With 1,4-dichloro-2-butyne as an initiator 1,4-Dichloro-2-butyne (244 mg, 2 mole) in THF (16 mL) was added dropwise at 0°C to a solution of di-Grignard reagent 57 (1 mole) prepared from 45 (1 mole) and mag- nesium turnings (120. mg, 5 mole) with ethylene dibromide (570 mg, 3 mole) as entrainer. The solution was refluxed overnight and extracted with ether. The solution was washed with water and evaporated under vacuum to afford a white solid which was chromatographed on silica gel with hexane 166 as eluent to give 224 mg (80%) of 4 and 15 mg (5.4%) of 58. (e) With cuprous bromide as an initiator Cuprous bromide (460 mg, 3.3 mmole) was added to the di-Grignard solution of 57 (1.5 mmole) in 30 mL of THF at -78°C. The solution was stirred at -78°C for an addi- tional 1 h and the solution was warmed up to room tempera- ture with stirring overnight. Methanol was added to quench the solution and chloroform was added to extract the solu-. tion. The organic layer was washed with 4N HCl solution and water. The residue from evaporation of the solvent was chromatographed on silica gel with hexane as eluent, to give 380 mg (90%) of 4 and 25 mg (8.8%) of 58. 17. Preparation of 51 from 55 with n-BuLi and trimethyl- silyl chloride n-BuLi (2.4 M, 1 mL) was added to a stirred solution of 55 (532 mg, l mmole) in 25 mL of ether at -78°C under argon. The mixture was stirred at ~78°C for 30 min and then 3 mL of trimethylsilyl chloride was added and the mixture was warmed to room temperature. The organic layer was washed with water and dried over M9804. Evaporation of the solvent gave 380 mg (90%) of 51, mp 113-115°C. 167 18. Attempt to dimerize 55 with n-BuLi and CuCl2 n-BuLi (2 M, 1.4 mL) was added to a solution of 55 (680 mg, 1.3 mmole) in 15 mL of THF at -78°C under argon. The solution was stirred for 30 min and cupric chloride (385 mg, 2.8 mole) was added. The mixture was kept at -78°C for an additional 1 h and stirred overnight at room temperature. The solution was quenched with methanol and then ether (100 mL) was added. The organic layer was washed with aqueous HCl (4 M) and water. The residue from evapora- tion of the solvent was chromatographed on silica gel with hexane as eluent to give 4 (180 mg, 50%) and 58 (45 mg, 16%). 19. Attempt to dimerize 55 with Ni(P¢3_)_3 as catalyst Ni(P¢3)3 (0.25 mmole) was prepared from Ni(P33)2C1227b (160 mg, 0.25 mole), zinc (32.5 mg, 0.5 mole) and P¢3 (52.5 mg, 0.2 mole) at 50°C in 10 mL of DMF.25b Compound 55 (300 mg, 0.56 mole) was added to the catalyst solution at 50°C. The mixture was kept at 50°C for 20 h with stirring. Then the mixture was washed with aqueous HCl (6 M) and water. Chloroform (100 mL) was added to extract the product. The organic layer was washed with water again and dried over MgSO4. Evaporation of the solvent gave recovered starting material quantitatively. 168 20. 1,8-Bi8(4'-trimethylsily1biphenyl)naphthalene (66) and 1-(4'-trimethylsily1biphenyl)naphthalene (69) A solution of 10 mmole of 4'-trimethylsilylbipheny1-4- magnesium bromide was prepared from 3.05 g of 4-bromo-4'- trimethylsilylbiphenyl and 0.24 g of magnesium in 20 mL of THF with ethylene bromide as an activator. The solution was added to 1.30 g of zinc chloride in 10 mL of THF and stirr- ed for 1 h at room temperature. This mixture was added to 1.0 g (3.0 mmole) of 1,8-diiodonaphthalene with. 10% of Ni(P (1)3)4 in 20 mL of THF. The solution was stirred over- night at room temperature under an argon atmosphere and washed with 6 M hydrochloric acid, then with water. The solution was extracted with 100 mL of ether and dried over MgSO4. After evaporation of the solvent, the mixture was chromatographed on silica gel with. hexane as (eluent to yield 339 mg (20%) of 66, mp l98-200°c and 450 mg (43%) of 69, mp 162-164°C. For 66: 1m (60 MHz, cnc1) 67.85-6.80 (m, 22H), 3 0.25 (s, 18 H); 13cm: (20 MHz, coc13) 6141.17, 139.48, 134.48, 131.92, 131.54, 131.36, 129.80, 128.58, 128.44, 127.69, 127.41,.127.19, 127.00, 126.18, 1.02, IR (KBr) 3040 (w), 2940(w), 1595(m), 1485(m), 1400(m), 1250(8), 1000(8), 800 cm-l(s); mass spectrum, m/g (rel. intensity) 576 (4), 504(5), 489(6), 450(16), 435(16), 378(32), 363(39), 73(100); high resolution mass spectrum: calculated m/e 169 for C H oSi2, 576.26687; observed: m/g 576.26708. 40 4 For 69: 1mm (60 MHz, cuc13) 67.90-7.0 (m, 15H), 0.28 (s, 98); 13cm (20 MHz, 00013) 6145.50, 142.33, 141.21, 140.96, 140.46, 134.98, 132.76, 131.58, 129.39, 128.79, 128.61, 128.45, 128.25, 128.06, 127.54, 127.14, 126.88, 126.48, 1.06; IR (KBr) 3020(w), 2940(w), 1600 (m), 1490(m), 1390(8), 1250(8), 1100(8), 800 cm-1(8); mass spectrum, mfg (rel. intensity) 352(4), 337 (100), 276(7); high resolution mass spectrum: calculated m/g for C25H24Si; m/g 352.16473; found: g/g 352.166994. BI ELI OGRAPHY 10. 11. 12. BIBLIOGRAPHY OF PART I M. J. S. Dewar, A. J. Harget, N. Trinajstic, and S. D. WOrley, Tetrahedron, 26, 4505 (1970). (a) L. F. Fieser and M. J. Haddadin, Can. J. Chem., 43, 1599 (1965); (b) R. McCulloch, A. R. Rye, and D. Wage, Tetrahedron Lett., 5231 (1969); (c) W. S. Wilson and R. N. Warrener, ibid., 5203 (1970). R. Mayer, H. Kleinert, S. Richter, and K. Gewald, J. Prakt. Chem., 20, 244 (1963). R. Kreher and J. Seubert, z. Naturforsch. B, 20, 7S (1965). (a) Isoindole: J. D. White and M. E. Mann, Adv. Heterocycl. Chem., 11, 113 (1969); (b) Benzo[c]thio- phene: B. Iddon, ibid., 14, 331 (1972); (c) Isobenzo- furan: W. Friedrichsen, ibid., 26, 135, (1978). M. H.'Pa1mer and S. M. F. Kennedy, J. Chem. Soc., Perkin trans. 2, 81 (1976). W. Rettig and J. Wirz, Helv. Chim. Acta, 59, 1054 (1976). E. Chacko, J. Bornstein, and D. J. Sardella, J. Am. Chem. Soc., 99, 8248 (1977). - P. Crews, R. R. Kinter, and H. C. Padgett, J. Org. Chem., 38, 4391 (1973). (a) J. Kopecky, J. Shields, and J. Bornstein, Tetrahedron Lett., 3669 (1969); (b) B. A. Hess, L. J. Schaad, and C. W. Holyoke, Tetrahedron, 28, 3657 (1972); (c) B. A. Hess and L. J. Schaad, Tetrahedron Lett., 535 (1977). J. Kopecky , J. E. Shields , and J. Bornstein , Tetrahedron Lett., 3669 (1967). D. F. Veber and W. Lwowski, J. Am. Chem. Soc., 86, 4152 (1964). 170 13. 14. 15. 16. 17. 18. 19. 20. 21." 22. 23. 24. 25. 26. 27. 28. 29. 30. 171 R. H. Schlessinger and I. S. Ponticello, J. Am. Chem. C. O. Bender and R. Bonnett, J. Chem. Soc. (C), 3036 (1968). C. O. Bender, R. Bonnett, and R. G. Smith, J. Chem. Soc. (C), 1251 (1970). O. Dann, M. Kokorudz, and R. Gropper, Chem. Ber., 87 140 (1954). V. Schomaker and L. Pauling, J. Am. Chem. Soc., 61, 1769 (1939). H. C. Longnet-Higgins, Trans Faraday Soc., 45, 173 (1949). A. Mangini and C. Zauli, J. Chem. Soc., 2210 (1960). D. T. Clark, Tetrahedron, 24, 2663 (1968). R. H. Schlessinger and I. S. Ponticello, J. Am. Chem. Soc., 89, 3641 (1967). R. H. Schlessinger and A. G. Schultz, J. Am. Chem. Soc., 90, 1676 (1968). M. P. Cava and G. E. M. Husbands, J. Am. Chem. Soc., 91, 3952 (1969). ' M. P. Cava, M. Behforouz and G. E. M. Husbands, J. Am. Chem. Soc., 95,2561 (1973). . M. P. Cava, and M. V. Lakshimikantham, Acc. Chem. Res., 8, 139 (1975). M. P. Cava and A. A. Deana, J. Am. Chem. Soc., 81, 4266, (1959). (a) A. J. Barkovich, E. S. Strauss and K. P. Vollhardt, J. Am. Chem. Soc., 99, 8321 (1977); (b) A. J. Barkovich, K. P. Vollhardt, J. Am. Chem. Soc., 98, 2667 (1976). (a) H. Hopff and A. K. Wick, Helv. Chim. Acta, 43, 1473 (1960); (b) ibid., 44, 19 (1961). H. Hart and M. Sasaoka, J. Am. Chem. Soc., 100, 4326 (1978). O. Hinsberg, Chem. Ber., 43, 901 (1910). 31. 32. 33. 34. 35. 36. 37. 38. 39. 40. 41. 43. 44. 45. 46. 47. 48. 49. 172 D. W. H. MacDowell and Maurice H. Maxwell, J. Org. Chem., 35, 799 (1970). M. P. Cava, N. M. Pollack, O. A. Mamer and M. J. Mitchell, J. Org. Chem., 36, 3932 (1971). D. W. H. MacDowell, A. T. Jeffries and M. B. Meyers, J. Org. Chem., 36, 1416 (1971). R. M. Acheson, "An Introduction to the Chemistry of Heterocyclic Compounds", 3rd ed, Wiley, New York, N.Y., 1967, p. 157. B. D. Tilak, H. S. Desai and S. S. Gupte, Tetrahedron Lett., 1953 (1966). E. Ghera, Y. Gaoni and D. H. Perry, J. Chem. Soc., Chem. Comm., 1034 (1974). Y. Tamuara, H. Matsushuma and M. Ikeda, Synthesis, 277 (1974). M. P. Cava and N. M. Pollack, J. Am. Chem. Soc., 88, 4112 (1966). P. Friedman and P. Allen, Jr., J. Org. Chem., 30, 780 (1965). R. Kreher and K. J. Herd, Heterocycles, 11, 409 (1978). W. Tagaki, K. KiKukawa, K. Ande, and S. an, Chem. Ind. 1624 (1964). H. Wynberg, J. Feijen, and D. J. Zwanenburg, Rec. Trav. Chim., 87, 1007 (1968). L. E. Saris and M. P. Cava, J. Am. Chem. Soc., 98, 867 (1976). . C. J. Horner, L. E. Saris, and M. P. Cava, Tetrahedron Lett., 2581 (1976). R. H. Schlessinger, G. S. Ponticello, A. G. Schultz, I. S. Ponticello, and J. M. Hoffman, Tetrahedron Lett., 3963 (1968) . K. Naito and B. Rickborn, J. Org. Chem., 45, 406 (1980). M. A. Makhlouf and B. Rickborn, J. Org. Chem., 46, 2734 (1981). J. Bornstein and R. Hardy, J. Chem. Soc., 612 (1980). 50. 51. 52. 53. 54. 55. 56. 57. 58. 59. 60. 61. 62. 63. 64. 65. 66. 67. 173 J. E. Shield, D. E. Remy, and J. Bornstein, J. Org. Chem., 40, 477 (1975). E. Hammerschmidt, W. Bieber, and F. V6gtle, Chem. Ber., 111, 2445 (1978). (a) H. Wynberg and D. J. Zwanenburg, Tetrahedron Lett., 761 (1967). (b0 F. Challenger, Science Pro- gress, 41, S93 (1953). M. P. Cava and N. M. Pallack, J. Am. Chem. Soc., 89, 3639 (1967). H. Wynberg and D. J. Zwanenburg, J. Org. Chem., 29, 1919 (1964). D. J. Zwanenberg and H. Wynberg, J. Org. Chem., 34, 333 (1969). M. P. Cava, N. M. Pollack, and G. A. Dieterle, J. Am. Chem. Soc., 95, 2558 (1973). R. M. Dodson and R. F. Sauers, J. Chem. Soc., Chem. Comm., 1189 (1967). J. R. Grunwell, D. L. Foerst and M. J. Sanders, J. Org. Chem., 42, 1142 (1977). (a) S. Gronowitz and T. Dahlgren, Chemica Scripta, 12, 56 (1979). (b) ibid, 12, 100 (1979). A. Wiersema and S. Gronowi‘tz, Acta Chem. Scand., 24, 2593 (1970). (a) K. Clarke, D. N. Gregory, and R. M. Scrowston, J. Chem. Soc., Perkin I, 2956 (1973) (b) ibid., J. Chem. Soc., C, 537 (1969). ' M. Sasaoka, Thesi8., M.S.U., (1978). E. Giovannini and H. Vuilleumier, Helv. Chim. Acta, 60, 1452 (1977). D. J. Zwanenburg and H. Wynberg, Rec. Trav. Chim., 88, 331 (1969). R. C. Fuson and C. H. McKeever, Org. Reaction, 1, 63 (1942). L. F. Fieser, J. Am. Chem. Soc., 51, 951 (1929). A. Oku, T. KaKihana, and H. Hart, J. Am. Chem. Soc., 89, 4554 (1967). 10. 11. 12. 13. BIBLIOGRAPHY OF PART II D. J. Cram and H. Steinberg, J. Am. Chem. Soc., 73, 5691 (1951). V. Boekelheide, Acc. Chem. Res., 13, 65 (1980). D. J. Cram and J. M. Cram, Acc. Chem. Res., 4, 204 (1971). F. V6gt1e and J. Griitze, Angew. Chem. Int. Ed., 14, 559 (1975). N. Jacobson and V. Boekelheide, ibid., 17, 46 (1978). H. 0. House, R. W. Magin, and H. M. Thompson, J., Org. Chem., 28, 2403 (1963). (a) H. 0. House, W. J. Campbell, and M. Gall, ibid., 35, 1815 (1970). (b) R. L. Clough and J. D. Roberts, J. Am. Chem. Soc., 98, 1018 (1976). M. Rabinovitz, I. Agranat, and E. D. Bergmann, Tet. Lett., 4133 (1965). ' H. 0. House, D. Koepsell, and W. Jaeger, J. Org. Chem., 38, 1167 (1973). R. L. Clough, W. J. Kung, R. E. Marsh, and J. D. Roberts, J. Org. Chem., 41, 3603 (1976). W. Bieber and F. V6gtle, Angew. Chem. Int. Ed., 16, 175 (1977). R. Wingen and F. Végtle, Chem. Ber., 113, 676 (1980). D. Schweitzer, K. H. Hausser, and M. W. Haenel, Chem. Phys., 29, 181 (1981). 174 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 175 (a) R. L. Clough, D. Mison, and J. D. Roberts, J. Org. Chem., 41, 2252 (1976). (b) A. Minato, K. Tamao, T. Hayashi, K. Suzuki, and M. Kumada, Tet. Lett., 845 (1980). (c) D. G. Morrel and J. K. Kochi, J. Am. Chem. Soc., 97, 7262 (1975). (d) R. C. Larock and J. Bernhardt, J. Org. Chem., 42, 1680 (1977). (e) A. McKillop, L. F. Elson, and E. C. Taylor, Tetrahedron, 26, 4041 (1970). (f) S. M. Neumann and J. K. Kochi, J. Org. Chem., 40, 599 (1975). (g) R. S. Smith and J. K. Kochi, J. Org. Chem., 41, 502 (1976). (h) K. Tamao, K. Sunitani, and M. Kumada, J. Am. Chem. Soc., 94, 4374 (1972). (i) P. E. Fanta, Chem. Rev., 64, 613 (1964). (j) G. Olah, Ed., "Friedel-Crafts and Related. Reactions", Vol. 2, Interscience, New York, N.Y., 1964, p. 979. (k) J. March, "Advanced Organic Chemistry: Reactions, mechanism and structure“, McGraw-Hill, New York, N.Y., 1968, p. 523. (1) R. W. Hoffmann, "Dehydrobenzene and cycloalkynes", Academic Press, New York, N.Y., 1967, p. 106-108. .A. S. Bailey, G. A. Dale, A. J. Schuttleworth, and D. P. weizmann, J. Chem. Soc., 5110 (1964). H. 0. House and R. W. Bashe, II, J. Org. Chem., 32, 784 (1967). H. 0. House and R. W. Bashe, II, J. Org. Chem., 30, 2942 (1965). H. 0. House, D. G. Koepsell, and W. J. Campbell, J. Org. Chem., 37, 1003 (1972). K. Tamao , K. Sumitani , Y. Kiso , M. Zembayashi , A. Fujioka , S . Kodama , I . Nakajima , A. Minato , and M. Kumada, Bull Chem. Soc. Japan, 49, 1958 (1976). C. Eaborn, D. R. M. Walton, and D. J. Young, J. Chem. Soc., B, 15 (1969). R. L. Funk and K. P. C. Vollhardt, J. Chem. Soc. Chem. Comm., 833 (1976). E. Negishi, A. 0. King, and N. Okukado, J. Org. Chem., 42, 1822 (1977). T. Kauffmann, B. Greving, J. K6nig, A. Mitschker, and A. Wolterman, Ang. Chem. Int. Ed., 14, 713 (1975). R. H. Mitchell, B. N. Ghose, and M. E. Williams, Can. J. Chem., 55, 210 (1977). (a) A. S. Kende, L. S. Liebeskind, and D. M. Braitsch, Tet. Lett., 3375 (1975). (b) M. Zembayashi, K. Tamao, J. Yoshida, and M. Kumada, Tet Lett., 4089 (1977). 26. 27. 28. 29. 176 S. K. Taylor, S. G. Bennet, K. J. Heinz, and L. K. Lashley, J. Org. Chem., 46, 2194 (1981). (a) R. A- Schunn, Inorganic Synthesis, 15, 5 (1974). (b) catalysts are purchased from Alfa products. P. S. Johnson, and W. A. Waters, J. Chem. Soc., 4652 (1962). L. F. Fieser and M. Fieser, ”Reagents for Organic Syn- thesis”, 1, 502 (1967). ”'Wllifitiigfiujlfliflhjitwillimimiliflmm‘“ 5 624