.. . . .. 71...... 4......a...a.p ::.-.;:f..- (...... r..:_ . . . . v... —. ...r - — a n - I G u 49:... a? . m. / , . . I ; . . , l . 5:: . LI}. 2.x... _ ......x .. £21... ... . .1. . . 2...: .... _. .92....— _ . Kai/J...’ _ (H. ... . . j J :r .Cc .. a a . , 2 , _ n..,my.....a/J. ft... . ./ fi/J . (C, .5.../4 ......4. .. {Em/.... City/1' . E ....z nun/1.x . ..l. 7!, ... ,7. ...: «“442 .4. . a... tun/ll ‘ . Ito—... .....Lx... . 7/1.? 4 ”1.1.. 4/ A A. '17.; $5770 .1. . 7, . . .. .1 4. Ix. . _. q 29/. /, _ ,3” ”W? fl? . :5, ”$7., «a ..r 4 flit»? if ~ . w . ., I 64.. ... . . 4 . 9. «Kiel/if xx ,.,'./. . y 41-. v. IfiWWW/Kt y » wiwzawwy. ,, “VA. ” . J- }.rfiI/I 1. xxx I ”6» v/ ¢ u _. 5.0 «F' u f y v If» .uafluumeMaVn, .. . yr , .J Mia. W435i“ 1.. ... . 9. , . fifffizm a , , . .zwr ;. . : . ‘ . 212.“; .52.. . 1...: ‘ . , ; a r iv?) ,. 4.1%.. fifafi. ...(nxf. LIBRARY Michigan 5'33 ‘ University ‘ . . l .4 ”5‘ “ This is to certify that find thesis entitled SYNTHETIC APPROACHES TO 6 , 9 : 19 ,22—DIIMINO- 2 , 26:13 , 15—1313 (DIMETHYLETHENO)-10, 12 :23,25- BIS (TRIMETHYLENE)—3 , 7, 8,18, 20, 21—HEXAMETHYL- 1 , 14—DIAZA[26] ANNULENE presented by Thomas Lee Bowman has been accepted towards fulfillment of the requirements for %degree in _C_h. emis tr Y Major profess r Diem ...: ' "‘5 the,“ “w" 0-7639 ‘ 5 ‘1 srnmaponrwcmsnj ‘ a +4 ABSTRACT SYNTHETIC APPROACHES To 6,9:19,22—DIIMINO-2,26:13,15- BIS (DIMETHYLETHENE )—10, 12 :23 , 25-1313 (TRIMETHYLENE )- 3,7,8,18,20,21—HEXAMETHYL—1,14—DIAZA[26]ANNULENE BY Thomas Lee Bowman Several synthetic pathways to the preparation of a substituted 1,14—diaza[26]annulene, 78 -— a potentially aromatic macrocycle -— were investigated. The 1,14— diaza[26]annulene Chosen was 29; 7:: In the course of the investigation several tri— and tetra—substituted pyrroles were synthesized for the various pathways attempted. 2,5—Bis(3—oxobutenyl)—3,4—dimethyl— Pyrrole, 9A” was prepared by a Michael addition of one equivalent of 3,4-dimethylpyrrole,QQJwith two equivalents of 3—butyn-2—one, §Zf Reduction of Q} with NaBH4 gave 2,5- biS(3-hydroxybutenyl)—3,4—dimethylpyrrole, 92; Thomas Lee Bowman 2,5-Bis(3-oxobutyl)—3,4-dimethylpyrrole, 22/ was also ob- tained by the Michael addition of §Q on methyl vinyl ketone as was 2; from §2 and gz. Ethyl 3—(3,4—dimethylpyrrol—2—yl)— propenoate, 22/ was formed by another Michael reaction of g2 on ethyl propiolate. Reduction of 22 gave ethyl 3-(3,4- dimethylpyrrol—Z—yl)propanoate, 122, which in turn reacted again with ethyl propfliate to give ethyl 3-(5-carbethoxy- ethyl-3,4—dimethylpyrrol—2—yl)propenoate, 12}, Reduction of lgl gave diethyl 3,4—dimethylpyrrole—2,5—dipropanoate, 122, Compound 122 could be converted into the N,N-dimethylamide derivative, N,N,N',N‘,3,4—hexamethylpyrrole—2,5—dipropanamide, Egg. The 3,4-dimethylpyrrole Grignard attack on fig and £22 to give 21 and 122 was unsuccessful. The Vilsmeier acylation of §Q using 122 also failed to give {23. Preparation of two new dipyrryltrimethine salts were successful. Reaction of dihydroresorcinol, 11%} with Q; gave 3,4,3‘,4‘-tetramethyl-dipyrryl—(2,2')—hexacyclotri- methine iodide, iii: Compound l9§ was reduced to 1,34bis- (3,4—dimethylpyrrol-2-yl)Cyclohexane, ligf 5,5'—Bis(oarb— ethoxyethyl)—3,4,3‘,4'~tetramethyl—dipyrryl—(2,2')—hexacyclo— trimethine iodide, le,was also prepared by the reaction of 113 with 199; Spectral data for all the above compounds and other reactions of them are given. SYNTHETIC APPROACHES TO 6, 9:19,22-DIIMINO-2 ,26:13,15— BIS (DIMETHYLETHENO) —10, 12:23,25-BIS (TRIMETHYLENE) - 3 , 7, 8, 18,20 ,21—HEXAMETHYL—1 , 14-DIAZA[26]ANNULENE BY Thomas Lee Bowman A DISSERTATION Submitted to Michigan State University in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY Department of Chemistry 1973 g 2’5 527.2, To my wife who has endured much over the past five years and has been a continuing source of encouragement; To my parents who have given me so much. ii ACKNOWLEDGMENTS I would like to thank the Department of Chemistry at Michigan State University for providing financial support in the form of teaching assistantships for the past five years, which encouraged me to seek a teaching career. I would also like to acknowledge Dr. Eugene LeGoff for his interest in and the conception of the project. Thanks also goes to my fellow graduate students, Dean Ersfeld, Ara Yeramyan, Stamatios Mylanokis, Eugene Losey, and Thomas Kowar, who made life a little easier to bear during hard times. And above all, thanks to God, who controls the particles of this world and has allowedrmeto mafipuhie them in this synthesis. TABLE OF CONTENTS INTRODUCTION . . . . . . . . . . . . . . . . . . . . Historical Development of the Concept of Aromaticity . . . . . . . . . . . . . . . . . Aromaticity in the Annulenes . . . . . . . . . Aromaticity in the Hetero—annulenes . . . . . . Purpose of Present Investigation . . . . . . . DISCUSSION AND RESULTS . . . . . . . . . . . . . . . EXPERIMENTAL . . . . . . . . . . . . . . . . . . . General Procedures . . . . . . . . . . Ethyl 3, 4— —dimethylpyrrole—2—carboxylate 83 and ethyl 4, 5-dimethylpyrrole—2—carboxylatew 84 Separation of ethyl 3 ,4-dimethylpyrrole-2—car- boxylate 83 and ethyl 4, 5— —dimethylpyrrole—2- carboxylate 84 —— ethyl 3, 4— —dimethyl— —5— iodo— pyrrole—2— —carboxylate 85 and ethyl 4, 5-dimethyl- 3-iodopyrrole-2- -carboxylate 86 . . . . . . Reduction of ethyl 3 ,4-dimethyl— —5- -iodopyrrole— 2- -carboxylate 85 and ethyl 4, 5— «dimethyl- -3— iodopyrrole—Z— Carboxylate 86 . . . . . . . 2,5—Bis(3-oxobutenyl)—3,4—dimethylpyrrole 21 . 2,5—Bis(3-hydroxybutenyl)—3,4—dimethylpyrrole 22 2,5—Bis(3—oxobutyl)—3,4-dimethylpyrrole 25 . . Ethyl 3—{3,4-dimethylpyrrol—2—yl)propenoate 22. Ethyl 3—’3, 4—dimethylpyrrol—2yl)propanoate 100. Ethyl 3— (5 —carbethoxyethyl- -3 ,4—dimethylpyrrol— 2-yl)propenoate 101 . . . . . . . . . Diethyl 3,4—dimethylpyrrole-2,5—dipropanoate 1&2 N,N,N',N',3,4—Hexamethylpyrrole—2,5—d1propanamide 0 . ~ . . u o a - 0 c o o o a . o a o . Attempted synthesm of 3,4,3',4'—tetramethyl-di— PYrryl-(2,2')—hexacyclotrimethine bromide i9§x iv Page 17 20 22 48 69 69 69 71 73 73 74 75 75 7G 77 78 78 79 TABLE OF CONTENTS (Continued) Page 3,4,3', LTetramethyl—dipyrryl—(Z,2')—hexacyclo- trimethine iodide 115 . . . . . . . . . . . . 80 liggBis(3,5-dimethy1+4—ethylpyrrol—2-yl)propane . . . . . . . . . . . . . . . . . . . . . 81 1,3—Bis(3,4—dimethylpyrrol—2-yl)cyclohexane 116 81 pm Reaction of 1 ,3—bis(3, 4 —dimethylpyrrol—2—yl)cyclo- hexane 116 with 3—butyn-2—one 87, the attempted synthesis of1119 . . . . . . . . . . . . 82 5, 5'-Bis(carbethoxyethyl)—3, 4, 3' ,4'—tetramethyl— dipyrryl— (2, 2' )-hexacyclotrimethine iodide 122’ 82 APPENDIX . . . . . . . . . . . . . . . . . . . . . . 84 BIBLIOGRAPHY . . . . . . . . . . . . . . . . . . . . 117 LIST OF TABLES TABLE Page I. Annulenes . . . . . . . . . . . . . . . . . 24 II. Hetero—annulenes . . . . . . . . . . . . . . 38 III. Mass spectrum of ethyl 3 ,4—dimethyl— —5— iodo— pyrrole-2 -carboxylate, 85 . . . . . . . . 107 IV. Mass spectrum of ethyl 4 ,5—dimethyl-3— —iodo— pyrrole-Z—carboxylate, 86 . . . . . . . . 108 V. Mass spectrum of 2,5—biS(3—oxobutenyl)—3,4— dimethylpyrrole, 91 . . . . . . . . . . . . 109 VI. Mass spectrum of 2,5-bis(3—oxobutyl)—3,4— dimethylpyrrole, 85’ . . . . . . . . . . . . 110 VII. Mass spectrum of ethyl 3—(3,4—dimethylpyrrol— 2—yl)propenoate, 82, . . . . . . . . . . . 111 VIII. Mass spectrum of ethyl 3—(3,4—dimethylpyrrol— 2-yl)propanoate, 100 . . . . . . . . . . . . 112 IX. Mass spectrum of ethyl 3—(5—carbethoxyethyl— 3,4-dimethylpyrrol—2—yl)propenoate, 101 . . 113 X. Mass spectrum of diethyl 3, 4— —dimethylpyrrole- 2 ,5 —dipropanoate, 102 . . . . . . . . . . 114 XI. Mass spectrum of 3, 4, 3' ,4'-tetramethyl- ~di— pyrryl— (2, 2' ) —hexacyclotrimethine iodide 115 115 vi FIGURE 1. 10. 11. 13. 14. LIST OF FIGURES Page Graph of delocalization energy XE number of w-electrons as calculated by HMO, PPP, and SPO methods . . . . . . . . . . . . . . . . . 11 Illustration of diamagnetic ring current effect . . . . . . . . . . . . . . . . . . . 14 Infrared spectrum of eth l 3,4—dimethylpyrrole— 2—carboxylate, 83 (CHCl3 . . . . . . . . . . 84 Infrared spectrum of ethyl 4,5-dimethylpyrrole— 2—carboxylate, 84,(CHC13).. . . . . . . . . . 85 Infrared spectrum of ethyl 3,4—dimethyl-5— iodopyrrole—2-carboxylate, 8Q (CHCls) . . . . 86 Infrared spectrum of ethyl 4,5-dimethyl—3— iodopyrrole-2-carboxylate, 86 (CHC13) . . . . 87 Infrared spectrum of 2,5—bis(3—oxobutenyl)—3,4- dimethylpyrrole, 211(KBr) . . . . . . . . . . 88 Infrared spectrum of 2,5-bis(3—hydroxybutenyl)- 3,4—dimethylpyrrole, 82’(KBr) . . . . . . . . 89 Infrared spectrum of 2,5—bis(3-oxobutyl)-3,4— dimethylpyrrole, 22 (liquid film) . . . . . . 90 Infrared spectrum of ethyl 3—(3,4—dimethylpyrrol— 2-yl)propenoate, 82 (CHCl3) . . . . . . . . . 91 Infrared spectrum of ethyl 3-(3,4—dimethylpyrrol— 2—yl)propanoate, 120 (CHCl3) . . . . . . . 92 Infrared spectrum Of ethyl 3-(5-carbethoxyethyl— 3,4—dimethylpyrrol—2—yl)propenoate, 101 (CHC13) 93 Infrared spectrum of diethyl 3,4—dimethyl— pyrrole—2,5—dipropanoate, 102,(CHC13) . . . 94 Infrared spectrum of 3,4,3',4'—tetramethyl- dipyrryl—(2,2')—hexacyclotrimeth1ne lOdlde,ll§, 9 . - - 5 (CHCla)................. vii LIST OF FIGURES (Continued) FIGURE 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. Page Infrared Spectrum of 1,3—bis(3,4—dimethyl- pyrrol-Z—yl)cyclohexane, 116 (CHC13) . . . . 96 Infrared spectrum of 5, 5'—bis(carbethoxyethyl)- 3, 4, 3' ,4'—tetramethyl—dipyrryl— (2, 2' )-hexa- cyclotrimethine iodide, 1291(CHC13 l . . . . . 97 NMR spectrum of ethyl 3,4—dimethylpyrrole—2— carboxylate, 83 (CDCl3) . . . . . . . . . . . 98 NMR Spectrum of ethyl 4, 5- -dimethylpyrrole— —2— carboxylate, 84 (CDCl3 ) . . . . . . . 98 NMR spectrum of ethyl 3,4—dimeth l—5-iodo- pyrrole—2—carboxylate, 851(CDC13 . . . . . . 99 NMR spectrum of ethyl 4,5—dimeth l-3—iodo- pyrrole—Z—carboxylate, 86 (CDCl3 . . . . . . 99 NMR Spectrum of 2,5—bis(3—oxobutenyl)-3,4— dimethylpyrrole, 91 ((CF3)C=O~1.5 H20) . . . 100 NMR Spectrum of 2,5-bis(3—hydroxybutenyl)— 3,4-dimethylpyrrole, 92,(CDC13) . . . . . . . 100 NMR spectrum of 2,5—bis(3—oxobutyl)—3,4— dimethylpyrrole, g§'(CDCl3) . . . . . . . . . 101 NMR spectrum of ethyl 3- (3, 4- -dimethylpyrrol- 2—yl)propenoate, 99'(CDC13) . . . . . . . 101 NMR spectrum of ethyl 3- (3, 4—dimethylpyrrol- 2—yl)propanoate, 100 (CD013). Insert: 100 MHz spectrum of A2B2 pattern at O 2. 66 . . . . . 102 NMR spectrum of eth l 3—(5—Carbethoxyethyl—3,4— dimethylpyrrol-Z—yl propenoate, 191/(CDC13) . 102 NMR Spectrum of diethyl 3,4—dimethylpyrrole— 2,5-dipropanoate, 102 (CDC13)- Insert: 100 MHz Spectrum of A2B2 pattern at O 2.67 . . . . . 103 NMR spectrum of 3, 4— —dimethylpyrrole-2, 5- dipropanoic acid, 104 (CDCla) . . . . . . . 103 NMR Spectrum of N,N,N',N',3,4—hexamethylpyrrole— 2,5—dipropanamide, 1251(CDC13). Insert; 100 Hz sweep width of Spectrum at 5 2.77 . . . . . . 104 viii LIST OF FIGURES (Continued) FIGURE 30. 31. 32. 33. 34. NMR Spectrum of 3,4,3“,4'—tetramethyl-di— pyrryl—(2,2')-hexacyclotrimethine iodide, 1}§,(cnc13) . . . . . . . . . . . . . . . . . NMR spectrum of 1,3—bis(3,4—dimethylpyrrol— 2-yl)cyclohexane, 1161(CDC13) . . . . . . . . NMR spectrum of biS-2—(3,5—dimethyl—4eethyl— pyrrole)trimethine bromide, 112’(CDC13) . . . NMR spectrum of 1,3—bis(3,5-dimethyl—4—ethyl— pyrrrol-2—y1)propane, 118 (CDCl3) . . . . . . NMR Spectrum of 5,5'-biS(carbethoxyethyl)— 3,4,3',4‘—tetramethyl—dipyrryl—(2,2')—hexa- cyclotrimethine iodide, 122’(CDC13) . . . . ix Page 104 105 105 106 INTRODUCTION One of the most actively investigated areas of organic chemistry over the past one hundred and eight years has been the concept of aromaticity. The metamorphosis of this con- cept is perhaps one of the best examples of the scientific method——the interaction of observable, experimental data with the theoretical explanations of that data. In 1865, Kekule proposed a cyclic array of six carbons involving three double bonds as the structure for benzene. Since then theoretical chemists have been trying to define and describe the factors in benzenoid compounds which give rise to the observations of substitution 22 rather than addition 32 the double bondS——a phenomenon which has been explained by the concept of armaticity. In the twentieth century the concept of aromaticity has been extended to non—benzenoid compounds also. In addition to the works of the theoretician, many synthetic organic chemists have tried to synthesize a wide variety of cyclic, conjugated molecules in order to better define the aromatic concept. It is in this light that the present investigation was undertaken. Prior to 1858 no clear theory of the molecular make—up of organic compounds existed. In the early 1800's the term "aromatic“ had been applied to any isolated compound which 4 2 had an aromatic odor, whether or not it contained a benzene ring. After 1830, when good combustion analysis became available, aromatic compounds were categorized according to composition——relatively high carbon to hydrogen ratio. Around the middle of the nineteenth century it was recognized that there was a nucleus common to these aromatic compounds with high carbon to hydrogen ratio, which was benzene char— acterized in 1825 by Faraday.1 Then in 1858 couper2 and Kekule3 simultaneously proposed the tetravalent character of carbon and various molecular structures based on that idea. This was the beginning of structural organic chem— istry. The first attempt to provide a structure for these aromatic compounds was made in 1858 by Couper. In 1861 Loschmidt4 put forth the idea of a cyclic structure for ben— zene but did not account for the tetravalency of carbon. He was the first to suggest that a six carbon nucleus was the basis for the aromatic compounds. Then in 1865 Kekule5 set the groundwork for the structural definition of aromatic compounds. He felt that a series of aromatic compounds analogous to the then known aliphatic series existed; the Simplest aromatic of this series had six carbons. It was in this 1865 paper that Kekule proposed the cyclic array of six carbons with alternating double and Single bonds, 1, for benzene. The remaining valences were used for bonding to atoms external to the Six-carbon nucleus. This structure accounted for the high carbon to hydrogen ratio but did not 3 satisfactorily explain the number of isomers for the substi- tuted benzene compounds. This was to be clarified in a later paper by Kekule. Erlenmeyer6 agreed with this six carbon structure pro— posed by Kekule but disagreed that benzene was the basic unit of the aromatics. He felt that the basis for the aroma- tics should not be a core of six carbons but rather their chemical behavior——substitution rather than addition. Thus was born the criterion of chemical reactivity rather than structure for a de8cription of aromatic compounds. Because of the dissymmetry of structure 1, Kekule could not account in 1865 for the limited number of substitution isomers found for benzene. He clarified this point in a paper in 1872.7 It was in this paper that Kekule suggested that due to interatomic collision of the carbons, the posi- tions of the double bonds over a period of time change. At any particular time, benzene has the structure I but at another time has structure 2. 1 ,2. Therefore, whether benzene has the structure 1 or 2 depends on when the molecule is observed. In other words, at any particular point in time, benzene may be seen as l or 2 but over a short time period, benzene is neither 1 nor 2 but a 4 combination of 1 and 2; In this way all carbon—carbon bonds become equal, the molecule becomes symmetrical, and thus the limited number of substituted isomers is observed. Note that Kekule did 29$ say that there is an equilibrium between the structures 1 and 2. Neither structure actually exists—— only a combination of the two. This idea is very close to the concept of resonance which was formulated some Sixty years later. The final structural definition of benzene by Kekule is that benzene is a planar structure consisting of a cyclic array of six carbons containing symmetrical bonds between carbons. However, Kekule's structure still did not explain why the aromatic ring reacted differently chemically from olefinic bonds. Immediately following Kekule's proposal in 1865, a plethora of structural explanations of the structure of ben— zene were put forth by such noted men of science as Erlen— meyer, claus, Ladenburg, Wichelhaus, Baeyer, and Meyer. The various proposed structures (3, 4, 5, 6, 7, and 8) did not enjoy a long life of acceptance. It was not until the 1890's Claus8 Ladenburg9 St'adeler,10 Wichelhaus11 3 4 g Meyer12 Armstrong13 Baeyer14 E 1 E that a sound attempt was made to explain the unusual chemi- cal reactivity of the aromatic compounds and relate this reactivity to the structure of the molecule and to the bonds involved. Bamberger15 in 1890 attempted to make this rela- tionship. He used the earlier proposed hexacentric struc- ture 8 and stated that the hexacentric bonds had the poten— tial for bonding. These centric bonds are held in an equilibrium state by some unknown force; this equilibrium is disrupted when the molecule reacts. Therefore, the mole— cule will rearrange or react in such a way upon disruption of this equilibrium as to restore the equflibrium position originally present. However, Bamberger's hypothesis lost favor because of the ill-defined forces which held the cen— tric valencies in equilibrium, and there was nothing at that time to confirm the exclusive use of six valencies. These valencies can be equated to today's concept of the electron. Therefore, Bamberger had in a way anticipated the electronic theory of benzene by thirty—five years. Finally in 1899 Thiele16 introduced the ideas of par— tial bonds and conjugation to explain the reduced character of some olefinic bonds to addition——for example, 1,4-addi- tion to conjugated dienes. Because of the reduced olefinic character of the double bonds due to this "conjugation",17 Thiele rationalized that the double bonds in Kekule's struc— ture of benzene are not true double bonds and therefore should not react like olefinic bonds. The use of conjuga— tion made all six carbon-carbon bonds equivalent and ex— plained the symmetry of benzene and its reduced olefinic character. This idea is used quite extensively today but was rejected at the turn of the century because in addition to the conjugation concept, Thiele stated that the only criterion for an aromatic compound was that it have alter— nating single and double bonds in a cyclic array to allow for conjugation. This latter statement was disproved and as a result Thiele's conjugation theory rejected when Will— statter was unable to synthesize cyclobutadiene18 and upon synthesizing cyclooctatetraene in 191319 a,b showed that it did not possess aromatic prOpertieS. With these results it appeared at the beginning of the twentieth century that there was a uniqueness to the "aromatic sextet” that im— parted the unique chemical reactivity to benzene. NO firm proposal existed as of 1915 which would enable the concept of aromaticity to be extended to compounds other than benzene. With the discovery of the atomic particles by Thompson, Townsend, and Millikan during the period of 1897 to 1908 and from these discoveries the development of the atomic theory by Rutherford, a new era opened up in which the concept of aromaticity was put on a broader and firmer base. With the rapid acceptance of the electronic theory of valence proposed by G. N.Lewis and others, Armit and Robinson20 in 1925 interpreted Bamberger's "potential valencies" as the idea of the "aromatic sextet". Robinson felt that the aromatic character and thus its chemical re- activity were due to the association of six valency eleg- trgns and these six electrons imparted properties to ben— zene much like the closed shell doublet of neon and the octet of the other inert gases. This "aromatic sextet" was symbolized by a circle and only meant the association of six electrons and not any particular linking of them. This con- cept of an "aromatic sextet" also afforded an explanation for the condensed benzenoid compounds. Thus, this was the first hypothesis that provided an explanation for the chemical reactivity and structure of aromatic compounds other than benzene. Every theory put forward up to and including Robinson's “aromatic sextet" was formulated in order to explain the peculiar chemical reactivity (a property of the transition state) of a class of compounds called aromatic. This ap- proach to the defining of aromatics was completely changed with the development of quantum mechanics in the 1920's and its initial use in the development of the valence bond theory by Heitler—London in 192721 and the molecular orbital theory by Hfickel in 1931.22 Both the valence bond and molecular orbital theories try to explain aromaticity on the basis of the ground state of the molecule rather than some transition state property. Both theories for the first 8 time enabled chemists to develop a theory of aromaticity to explain the basis for the chemical reactivity of aromatic compounds and also allowed them to predict aromatic charac— ter in yet unsynthesized compounds. The two theories ac- complished these things with different degrees of success because they were based on different assumptions. Valence bond theory regards a molecule as being com- posed of atoms which to a great extent retain their distinct character even when bonded. The complete atom is brought together with another atom, and in the process the orbitals overlap and the electrons interact to form the familiar two electron localized bond. In order to explain the bonding in the symmetrical benzene molecule, valence bond theory intro- duced the concept of "resonance" and "resonance energy". The idea of resonance is based on a set of wave func- tions for a molecule, each of which may be regarded as a reasonable approximation to the true wave function for the ground state. A suitably—chosen combination of these wave functions will then be an even better approximation to the true wave function.23 When this is done one obtains the wave functions which correspond to the two Kekule structures of benzene as the major contributing wave functions to the combination. Furthermore, an estimate of the energy based on the mixture of the functions will be lower than an esti- mate based on any of the individual functions making up the combination. This difference of energy between the mixture of functions and any individual function is called the 9 resonance energy. The reduced chemical reactivity of ben- zene as compared to three isolated olefinic bonds is a result of this resonance energy. The problem with the valence bond theory is that it predicts a Sizeable resonance energy per w-electron for such compounds as cyclobutadiene and cyclooctatetraene.24 This has not been observed and therefore its use as a predictive tool has been diminished. However, Linus Pauling tries to justify its use by saying: I feel that the greatest advantage of the theory of resonance, as compared to other ways (such as molecular orbital theory) of discussing the Structure of mole— cules for which a simple valence bond structure is not enough, is that it makes use of structural elements with which the chemist is familiar.25 Hfickel developed the molecular orbital theory and re— ported it in 1931. In MO theory orbitals on atoms are initially brought together and a linear combination of these atomic orbitals produces a series of molecular orbitals of differing energy. The electrons are then placed into these 1molecular orbitals starting with the lowest energy orbital ‘and filling each orbital of increasing energy according to Hund's Rule and the Pauli Exclusion Principle, until all the initially available electrons are used. Of course, this is not quite as easily visualized as the traditional idea of the two—electron localized bond. However, it provides better predictive ability than does the valence bond theory. As a consequence of Hfickel's MO theory, he was able to make a general rule which became known as Hfickel's Rule. It 10 states that "amongst fully conjugated, planar monocyclic polyolefins only those prossessing (4n + 2) v—electrons, where n is an integer, will have special aromatic stabil— ity."22 As a corollary, all similar systems with 4n F— electrons will not possess any special aromatic stability. This rule has been proven to work for many compounds with n < 3 and for some compounds where n > 3. However, there are the larger monocyclic ring systems where Hfickel's Rule and HMO theory begin to Show inconsist— encies. For example, in the larger annulenes, 2 > 4 ac- cording to HMO theory, the difference between localized (normal polyolefins) and delocalized ("aromatic”compounds) energy increases as ring size increases and the stability difference between (4n + 2) and 4n w-electron systems goes to zero at higher 2 values (see Figure 1).26 The latter statement has been shown to be true with the higher annul— enes. Those compounds which should Show aromaticity no longer do so but act like polyolefins. The former state— ment does not agree with the observed facts. The delocali— zation energy of the annulenes does not increase as the size of the ring system increases. In addition to this latter criticism, it is evident from Figure 1 that HMO theory predicts resonance stabilization for even the 4n Series. This has been shown to be untrue. The lower mem— bers of the 4n series actually Show a Sizeable destabiliza~ tion-—a negative delocalization energy.27 Thus Hfickel's Rule does give a good qualitative or relative prediction of 11 (eV‘ RE or DE —1.5P l L l 1 J,_l 1 4,.r11 1 1 I it, 4 6 8 10 12 14 18 22 26 30 W—Electrons Figure 1 aromaticity to monocyclic ring systems, but gives very poor quantitative results for delocalization energies. AS M. J. S. Dewar states: "The main value or the Huckel method lies in the facility with which it can be used to generalize chemical phenomena in a qualitative or even a semi—quanti- tative [for small values of n] manner."28 In order to remove the quantitative discrepancies of the HMO method, many theoreticians Since 1931 have sought better quantum—mechanical methods, using fewer or more logi- cal approximations in the calculations. M. J. S. Dewar published some of his work in 196526 in which he used three different methods to determine the delocalization energies Of the monocyclic, conjugated ring system known as the 12 annulenes. The results of the three methods are shown in Figure 1. The three methods were the HMO method, PPP method which is a combination of Pople's method and Pariser, Parr values, and finally the SP0 or split p-orbital method. The Hfickel method, of course, assumes a planar polygon geometry, equal carbon—carbon bond lengths, and no electron-electron repulsions and because of these assumptions gives the results previously discussed. The latter two methods were developed so as to eliminate these assumptions. The results shown agree fairly well with the available experimental data. Thus it is seen that the relative aromatic stabilities of the (4n + 2) w-electron and the 4n w—electron systems do ap— proach a common value as predicted by HMO theory and Hfickel's Rule; but contrary to HMO theory and consistent with experi— mental data, this value is not an ever-increasing delocaliza- tion energy but a value of zero delocalization energy. In addition, it accounts for the negative delocalization energies or antiaromaticity of the 4n series. The calcula— tions also show at approximately what value of n the (4n + 2) system becomes a simple polyolefin. This agrees with the observation that [22] annulene29 is Aromatic but that [30] annulenez9 is non—aromatic. Based on these results Dewar proposed the following definition for aromaticity:30 Cyclic conjugated systems are considered aromatic if cyclic delocalization of electrons makes a negative contribution to their heats of formation. It should be mentioned here that even Dewar‘s calculations 13 Show too rapid a decrease in resonance energy for the (4n + 2) w-electron system, but they have produced the closest agreement with experimental data for compounds hav- ing large n values. Figeys31 in 1970 confirmed Dewar's results by another MO method. Both Dewar's and Huckel's works were concerned with the resonance energy—~the extra stabilization imparted to the aromatic molecule by the cyclic conjugated arrangement of the double bonds. Dewar's calculations can be and in most cases have been verified by experimentally determined heats of combustion and hydrogenation. However, there is another measurable physical property of the olefinic com- pounds which has been used to categorize the aromaticity of these cyclic conjugated systems. This physical property is the diamagnetic anisotropy32133134 of the molecule, and the consequences of this property are the observed paramagnetic and diamagnetic chemical shifts in the NMR for the vinyl protons on the interior and exterior of the ring.35 This is a criterion which is concerned with the ground state of the molecule which has been perturbed very Slightly by the presence of a magnetic field. If a closed conjugated path about which w-electrons can circulate exists in a molecule, then upon being placed in a magnetic field, the field will induce a flow of the w- electrons around that circular path. The circulating elec- trons will in turn produce their own small magnetic field. If the circular path is perpendicular to the applied 14 external magnetic field, H0, then the induced magnetic field, H', of the circulating w—electrons will oppose the applied field (see Figure 2). This induced ring current and mag— netic field can be observed and has been used as a criterion for aromaticity.36 However, its direct measurement is dif— ficult and can only be done on crystalline material. As mentioned earlier, the effect of the induced ring current and magnetic field on the chemical shifts of protons in the NMR can be observed. This fact eliminates the prob— lem of using only crystalline samples; both liquids and solids can be used. Figure 2 illustrates the effect of the magnetic field on a proton externally attached to the ring and also indicates what would happen to a proton within the ring for a diamagnetic ring current. ,t— -+I~ \ / current I / \ / H \\ \\ / \ /’ \ Induced Vj/ ‘ field \\// Figure 2 15 A proton external to the ring feels the positive en- hancement of the applied magnetic field by the induced mag— netic field. Therefore, an external field, H0, smaller by the amount of the induced field, H', must be applied, and the resonance of that exterior proton will appear at a lower applied field value than for a linear olefinic proton. The reverse is true for a proton within the ring. The phenom— enon just described is due to a diamagnetic ring current. The opposite effect, exterior protons shifted up—field and interior protons shifted down—field, is caused by a para- magnetic ring current. If there is no significant shift of the olefinic protons from their normal value of 5 4—6, then there is no induced ring current present and hence no ex— tensive delocalization of w-electrons. It should be men— tioned at this point that an observed paramagentic or dia- magnetic ring current in a molecule can only give a quali— tative statement of w-electron delocalization and no quantitative statement. Sondheimer was the first to use this phenomenon exten- sively to determine the delocalization of m—electrons in the annulenes. These compounds are quite well suited for this technique because they possess both internal and external protons in different amount. So one can see both the up- field and down—field Shift of the protons when the magnetic effect is present. It has been observed by Sondheimer that the [4n] annulenes give rise to a paramagnetic ring current and that [4n + 2] annulenes cause a diamagnetic ring current. 16 It has further been observed that some of the higher annul- enes give only the chemical shifts of normal olefinic pro— tons: in other words, no w—electron delocalization. So it appears that the use of the magnetic anisotropy and NMR chem— ical shifts of molecules allows one to determine the pres— ence of w-electron delocalization and whether it is associ— ated with a 4n or (4n + 2) w—electron system. Hence, one has available a qualitative criterion for aromaticity. The results of the application of this criterion and of Dewar‘s and Hfickel's criteria to two series of monocyclic conjugated ring systems, the annulenes, and the hetero— annulenes will be presented in the next section. From this brief discussion of the history of the con— cept of aromaticity, one can see a Shift in emphasis from the use of odor and chemical reactivity in the 1800's to the use of ground state properties in the twentieth century as criteria for the definition of aromaticity; a broadening of the scope of aromaticity from benzene only to benzenoid compounds and finally to the non-benzenoid species; the use of MO theory with a variety of refinements to calculate and predict the ground state prOperties of the aromatic com— pounds; and the application of heats of combustion and hydrogenation and NMR chemical shifts to verify or nullify the calculations and predictions. 17 Aromaticity in the Annulenes Benzene is the second member of a series of moncyclic, alternant hydrocarbons with alternating double and single bonds which have either 4n or (4n + 2) out—of—plane v— electrons. This series is called the annulene series and each member is designated as either a [4n] annulene or a [4n + 2] annulene.37 Benzene is also the first member of i the [4n + 2] annulenes, and cyclobutadiene is the first mem— ; ber of the [4n] annulene series. Cyclobutadiene has re— sisted isolation to date despite many attempts and the only other annulenes which were synthesized prior to 1959 are benzene and cyclooctatetraene. Since then Sondheimer and co—workers have synthesized approximately thirty—six annulenes ranging from [12] annulene to [30] annulene. Al— though the isomer 22. of [10] annulene has not been iso— lated, probably as a result of the non-bonded hydrogen— hydrogen interactions within the ring, two other isomers (9b and 9c) have been isolated and characterized by Masamune?8 253 9,11 ‘19 Because the heats of combustion and hydrogenation for only benzene, cyclooctatetraene, and [18] annulene have been determined, quantitative confirmation for HUckel'S or Dewar's calculations can not be given, but the relative or 18 qualitative trends which their calculations predict can be observed by the NMR chemical shifts which arise as a result of the magnetic anisotropy of the molecules. This data for the annulenes and dehydroannulenes (annulenes with a triple bond) is given in Table I. It should be evident that the dehydroannulenes should still be able to sustain a ring current in a magnetic field just as the annulenes do be— cause they still have a continuous, cyclic array of out—of- plane v-electrons. It becomes apparent upon looking at the data that the [4n] annulenes Show a paramagnetic ring current as evidenced by the up—field shift of the external protons and the down— field Shift of the internal protons; the [4n + 2] annulenes Show a diamagnetic ring current as shown by the opposite shift of the corresponding protons. This phenomenon can only exist if the molecule can be planar. Any deviation from planarity will reduce correspondingly the amount of ring current. when the molecule iS quite non—planar, the ole— finic protons resonate at the normal values of T 4—6. This is evident for cyclooctatetraene and the lower members of the 4n and (4n + 2) series——compounds 9b” 93, 11, 12, £1, ii, 15, and 18: As the ring size increases above [12] annulene, the rings can become planar or nearly so, and they exhibit the necessary chemical shifts for 4n paramag- netic and (4n + 2) diamagnetic molecules. The NMR spectra are very temperature-dependent. This temperature depend- ency is the result of the flexibility imparted to the large 19 rings by the energy present at room temperature. This flexibility of the molecule allows the protons to become equivalent or nearly equivalent. As the temperature is lowered, the molecule becomes less and less flexible until it finally is rigid enough for one to observe the absorp- tions of the unique inner and outer protons. It is the s magnetic properties of the molecules at this inflexible L r 3 stage (after removal of the external effects of temperature) Q which should allow one to determine the aromatic character 5 of a molecule. According to Dewar's calculations and Hfickel's Rule, the (4n + 2) w—electron system should be aromatic and the 4n n—electron systems should be antiaromatic, the two sys- tems converging to nonaromaticity above 22 w-electrons. The NMR data verify these predictions. The [4n + 2] annulenes up to and including [22] annulene Show aromaticity; the [4n] annulenes show antiaromaticity. As expected, [24] annulene is not aromatic, but there is some ambiguity as to the aromaticity of [26] annulene. Monodehydro[26]annulene, 42, shows a small diamagnetic ring current, but 1, 9, 17—tri- dehydro[26]annulene, 43“ shows no ring current; in other words, it is polyolefinic in character. Although this ambiguity exists, the [26] annulenes appear to be almost, if not completely, polyene—like, because even though 42 shows a ring current, its effect is small. [28] Annulene has not been synthesized yet, although being a [4n] annul~ ene it might have a paramagnetic ring current providing 20 it is planar. NMR data is not available for the three im— pure [30] annulenes that have been reported by Sondheimer. However, their extreme reactivity towards decomposition seems to indicate that they are not aromatic and act like normal polyenes. From this data that is presently avail— able, it is still not certain that Dewar's prediction for disappearance of aromatic stability above 22 w—electrons is correct, at least for the annulenes. Further experimental data is needed. The hetero- annulenes discussed in the next section will provide some additional, but still incon- clusive, evidence for Dewar's predictions. Aromaticity in the Hetero—annulenes The hetero—annulenes are Species in which one or more of the carbon atoms in the annulene ring are replaced by a hetero—atom and/or the annulene ring is bridged by one or more hetero-atoms. The hetero—annulenes, porphyrins, cor— roles, and sapphyrins are examples of hetero-annulenes and are listed in Table II along with their NMR and UV spectral data. It has been shown that the perturbation of the annulene ring by the presence of the bridging nitrogen atoms and ethylenic bonds in the porphyrin ring system is quite small and these compounds do behave almost like the annulene hydrocarbons.38 Many workers (referemxs in Table II) have extended this fact to compounds with bridging atoms other than nitrogen; it appears that this extension is not un— reasonable. Because of these facts, one might expect that 21 the hetero—annulenes would possess Similar characteristics of aromaticity as do the annulenes corresponding to the presence of (4n + 2) or 4n w—electrons, providing that the molecule is planar. The effect of planarity on the aromaticity of (4n + 2) v—electrOn systems is very well illustrated by the hetero— annulenes. The attainment of aromaticity by the hetero- bridged [10] annulenes as compared to [10] annulene itself and the loss of aromaticity in the sulfur—bridged [18] an— nulenes are good examples of the importance of planarity. Isomer 92 of [10] annulene is non—planar because of the hydrogen-hydrogen interaction as stated in the previous section. Upon rem0val of those hydrogens and their replace— ment by either a —CH2- group (19), an —O- (42), or an —fiH- group (48), the molecule can become planar and the (4n + 2) v—electron system exhibits aromatic character. In the 18 #- electron system, 53” the space requirement for the three sulfur atoms is too large for the center cavity and so the molecule is non—planar and non-aromatic. For those hetero- annulenes in Table II that can become planar or nearly planar, a paramagnetic ring current for 4n systems and a diamagnetic ring current for (4n + 2) systems are observed. These observations are confirmed up to and including com- pound Zfiu a 4n w—electron system. No 26 or 28 w—electron system has been reported, so a gap in the critical area of Dewar‘s prediction exists. Finally, the 3D w-electron system, ZZ/ shows no aromaticity and acts like separate furan rings and ethylenic bonds. 22 Purpose of Present Investigation As stated in the previously presented history of aro— maticity, Dewar predicted that the loss of aromaticity and antiaromaticity for the (4n + 2) and the 4n w-electronic systems reapectively would occur above 22 v-electrons. Data from the annulenes of Sondheimer Shows good agreement up to the cut—off point of 22, but there exists some ambiguity in . , ‘EgaF-';'EXJ .- : .' PM “. the region of 26 w—electrons and higher. This ambiguity I also exists in the hetero~annulenes because no 26 or 28 n- electron systems have been reported. It is this gap in the experimental data in which a com- pound is needed to verify or refute Dewar's prediction that prompted the synthesis of a 26 w—electron system which pos— sesses bridging groups that would be expected to reduce the flexibility of the molecule and thus enhance the chances of its being planar. A molecule that might satisfy these re— quirements is compound Z83 It is a diaza [26] annulene which is bridged by two ethylenic groups and two imino groups. This molecule could conceivably be synthesized by starting with pyrrole and using reactions which have their precedence in porphyrin syntheses. Because both alpha and @323 positions in pyrrole are reactive Sites, it was de— sirable to block the beta positions; this was done by the use of methyl grOUps. A symmetrical substitution of two methyl groups was used to avoid the formation of structural isomers later in the synthesis. Upon introduction of two additional bridging groups into 18 later in the sequence, 23 the final 26 vr—electron system sought was the title compound 1%. 22, )2 mm n.oa P Aoom.m V mam mamasccm ow we mo.m u Aooo.mwe mam IflofiiocmgnmeIm.H oa inc me s.m n iooo.wov emm + Aaaooe mm mm . mamadccm o o 0 V 4 ma.w p Memo.mmv WNW IHoHiIvmaoImcmHn oH Amzv 2 o AoovIv AwnImmev “mouse mm mm .wm.v s new 2 manasccmfloHiImmflo oH Amzv , eImmsv nmm 2 o Aoovlv mom mzz .>.D oEmz ohm mucuUSHpm oeumE l IOU—1N .uoHQdoo oHQsoo n on xuoansop u p ”poamcam u m .uounmdv I g .um . I . . . . I . HmauHSE n E .HQ :0 m I Sm .oaumEOHmIcoz H o .uaumEoum H + uoflumcmmemnmm u m “DaumcmmEmao u Q “HMGMHQQOMHH M2 .mmcwasec< .H mHQMB 25 womasccmmmfigwcmfl me I InnuouIEmmImHo.mHo NH Amzv we “we wa.w e 0 sea AstH.mImm.mn Aoom.Hme ova Avaooc incnxntoHosoe ma Anema.mtAIoo.me 1am.av son mm ma AmVHv.oPAIHn.oP AwH.wv smva manasccm Amaoaov Afim.mv ammom Imoflirnnmmcao oa II Amzv as I Aws.mv nmmwm II. 0 ma “we om.o P ,mm.mv «em mu nuI ma any Hm.e u Amm.ay saw sea Asvo.mIH.m n Aww.wv mam “Naomoov n mod as ma any wn.ve as mm Asim5.mem.mt mamascnmfioaiomqnnanan Amzc mmH AEVNN.mev.NP Aoos.ofic own .suv.m.m.HImcmnnIocos OH 0 Avenue “oom.mme new mom mzz .>.D mEmZ we“ musuosuum UHMMM .Uwscflucoo .H manna 26 ma m / MI m I. \ / mamasccm r m an IfimfiiouesnmnaunIm.m.H NH 27 xx Ame me I VIA mm Ame wn.m e Aoom.wme wmm as m Awaoov chmuooomd mm1_flm.fimcxaemm.m n Sinai Mm1_mm.mmeimevm.m P r II mm MN A.m.mmv AEVNwofiu I._I GCTHSCCM \I \/ s E - IF x AmmMuwm memnwmmmwnv IflmfilouesnmemamIm H NH an A7 “awe mm" Aim .HIHC AUvmu DIP OOQA mm1_mm amefinooesm. «I Amwfic new as mm1_mm mmvxnemw. me Aoow.vme mam mm1_am.vmvxsvsv.mI Aoom.fimv van 3788 AmcmuUOOmi GCQHSGGM Io IflmfiiucmnInnumu we I 32.3; mom IemmImcmnunswnu mzv ma Ame mw.m I iooH.vmcsmwvm moa devo.mIm.m u Aoom.mmv own 3408 IwQMXQQOHomov . . II. oaumE mom mZz > D 282 ImII wusuosuum Iona .decfludoo .H magnum. 27 mamasccm on I . Aoos.v V was Ideaionnssmeocoz as imV mm innV s.oH I Aooa.s V mom as sea isVs.mIN.H P Aooo.mmV mam AmHOQOV AocmuooomHV .Wm AQEwu Ma o.oH I 30H ”MW mOH w.N p I x + A mHoooV I I EhmflpCMImm.m NE mINv.v mamasdcmfiwHV ma \\ .fl\Jfi\ we AmeEomH 03» on . mdflocommwnuoo Hum r // I m /_ I Canon CH mum mxmmmy . Tr // // I no I Amem.m t noon m V ohm AmZV mvH Amev.a H Aooo.mmV was I I o 1.9.mV AmaoooV “mamnoOOmHV mamascsw NH ImNHVOthnmpmHuou Im.s.m.HIfiwcmH>ans .UIHH Aoon.HmV ansvm InnnanmanINH.HH.e.m_ NH Hm Hm AmV we I . “oom.mmV mam hnIh. 0 sea ,stm.wIma.w e Aoom.mmV amm AoomIV AmHOQOV Auogqu mom mzz .>.D mEmZ mew ousuosnum oaumE Ion< .UQSCHuCOU .H mHQmB mm mm MNH meVom.v n HIH (U. o In P ioowaIVANmemomumoV mamascc<flmai ma AmV . IIIIIIII oooA o 7 I IoonVrmovaomw an moa imVsm.m e Aoom.ssV awn Abme AvHUUV chmuooomaV Aomm v has 22 Roam y now am Aoma W was Room.mm cos a Aoon.m V mam m mm m AoomHm V smm mImmI / Mwmm.m W WWW mamasccw ¢ mm 2 Aooo.smHV mom IfiaaionnsnnnannIm.m.H as vuquL/m AoV 8 I 2 mm ma AnV om.wa I AomH.m V men a m + mm Asymm.HImv.H p Aoom.m V Ham mm AEVHm.OImm.o n flowm.m V man 2908 AocmucodV Aoom.m V own I Aoom.mm V wmv mamasccm an we AeVms.o I Aoom.s V oHa Iflwaiounsanename.H as AQV as me AeVsm.H I Room.o V mos + mm Avam.nH e Aooo.msHV mom AmHUQUV Amcmuooomav mom mzz .>.D mEmz Iml # onsuosuum omwmm .UGSGHUCOU .H QHQMB a 29 mm & mHmEHOMCOU H. mm mumem all I . a: m AmeIV damn 30H In ncmHsccm .m . mm mm mew.mum.mw IImHIonnxrmnHIIIm.m.H eH .2 .I II in mH Aanm a I oooA an mH AEVm H I Aoom.HmV omm .= e mm IEVw.o I Room.va mIm HommV AmpIGCOHQOMV chmuooomHV am We n.v I :2: mm NM.W P LI mama mm AoowIV ooei nansccn //,.m 30H ImV ma AnImI.a I Aoom.me mam IImHIonnsamemHmIm.H mH .z mV Ms “InonH.a I Ioom.amV mwm 0 an we AanH.m I Aoom.oaV rmOIm HommV AochdouwowV AwsmuooowHV fl. mHoEHowGoo v mm mumem um mc & .AbomIV mama 30H In VII EN Apvm.m e mamasccm \ mm mm Ast.mIN.s I IHoHIOIUHLwanmIm.H mH =m : ImV mm Aanw.H I ooei 0 an mm IaVom.oI I Aooo.mmV Hmm .: mH Aano.mI I Aoom.mmV me : . AOOV Ammul mwGOumwOmV . or a; oaume mom mzz .>.D wemz IotH ousuosuum LOH< .pmchucoo .H mHQMB 30 H HGEOWH mamasccmmwfii IonnssonHIeImH.I.H mamasccmmwfigahguwe ImanlvH.mH.w.h.N.H mcwHSCCmfiwHV AomH.H V mmv “oom.wH V mam Aoom.HH V mam AOOI.NH V nwm oma.w V wIm omm.w V wen oom.m V awn ooo.omHV mmm oonNHHH «mm on oom.om W mHm ooH.mm man an a on mm Ineme.w I Woom.mm W Imm mm AEVH.mII.H I ooe.Im V mmm woomV AmHoooV AmcmpooomHV IIIIIII mes In Ham AmeV Astm.mH I AEVNI.o I mm Aoomlv I swam Aoow.Hm V was on as among w.HH Aoom.I V wow I xmmd Iooo.momV mom we mmH among H.H I AooH.m V wIm AwUImmBV chmuUOOmHV mom MZZ .>.D QEMZ wH wtfi mHWIOSH UflumE p um IOH¢ .©®SCHUCOU .H QHQmB i ii i I mamascsmflwHHOthnmo VINII mnHoquOImo :H mHsnIns Aoom.nH V mHv IHIIIIH.HH.nIHsaInE wH . I s IQV quaoIcH on wanna Ioom.aH V mam ImxeraH.mH.w.s.m.H a/Iwn& + In Hsoo mm omeHmHsnmn Aooo.ovHV Hmm . .I ,,: moI ov.I I AOOI.mm V mmm .1» 0-1 AmHoooV AmaV 1 3 omw.mH V one 22 oow.oH V mow mm ooo.mH V Iwm oooww V own oom.w W Obm HH HmEowH I II I ono.w V Imm I \ -n / ; 1%.“.me WWW 322.35: I I V083: Sm 5323.31.15. ... .1 \ / ... EV ooo.mm V mHm + woommwm V on 2 x S mm ,oon.mm W mom M“)n\r 3. saw . ....m . mm AEVa.mII.H I Ioom.om V «mm AnomV AvHUUV AoCMHOOOmHV mom mzz .>.D wEmZ leek muduoduum omwwm UwDCHuCOU .H mHnme 32 ocmHsccmflomI on 13V on o MmH AeVm.mIv.m I mI Ast.oAIVIm.mI I Aooo.esHV mam HomoHIV AwolmmBV AHwLumV om» I now oomNIHI mwm oom.mHV wIm ooa.I V mom ooo mHW Inn . n m m 5%.? .m .Mm.......e3...3 .. a an Wooo.HaV mHm I tInH mH a I m H + . oom.m V own mm m I Aoom.HmV mmm Aoom.mmV I m AwaooV “osmxmsoao oV ommwm V «Ha com «HV mam ommHmH mwm ooH.w va Voow.w mom a... 33.3 .. 3 NOOOImmw hNMlOHmuthme-IHHOQIMHINIMIH + an I . - . Moom.mmV mHm mm AeVn mIm H I ooo.mmV Ian mm ,EVH.wI3.I I ,oom.oHV mam AaooV “VHOOV chmuooomHV Mom mzz .>.D oEmZ mhfi musuosnum oaumE I , I0H< Hoom.mH V was I A V AOOI.NH V one u mm E o In I ...—I ~ . ...: . .. 11an a. .. I... E . I . I me m H m 0 Icon mHV ammom AsVI.OImm.o I Hoom wH V swm AbmeV AmnImmeV AHmsInV mm mm mwnw W wcmHDcsm xmmm IHONIOInsgwnHmIHH.H om 13V 3 mm enonn nv.OI I Aooo.aI V own 0 3 no I. xmom mm among o.HI I mooo.moHV mHm HoowIV Implmmh AmsmuooomHV ow mamasccm mmH AeVI.mIo.a I iooo.amHI mam IHomiounsamnIocoe on AMV mm AEVH.oAIVIm.mII Aoow.vm V mom HoomIV HmnImmeV “HmsIoV mom mEZ .>.D wEmZ UHMME Ih. stuosnum IOH< 34 GQQHSCCM IH3NIOIeHronocos an 13V o no I oom A msH AsVo.oIm.3 I Aooo.emHH OIm mm AeVa.OIa.NII iooo.anV mam ioomIV imHTImIV $3 In an acmHacquamI an “IV mm Im.m I Hooo.mmHH mum 0 on mm m.HAIVIm.mII Hooo.meV com AoomIV imnImmHV ImeV Aooo.m Vnmmmv Hoom.mH V was IH ion mcwmemm .aV no I Hoom.HHVamwmv mm a r a mm 1+ mI AsVom.mImm.m I Hooo.mmHV mIm mmH AeVmI.mImm.H I Aoow.wm V owm ANHUNQO AnmgumV mom mzz .>.D mEmZ men wusuosuum 0HumE Nv Aoom.mH V one Aoom.3H V mmv nemquqm mm anrmew me I Hooo.mmHH mam IHmNIOInsnmnocoe + mm AEVo.oIm.m I Hooo.HmHV OIm mmH Ast.mIH.m I Aoow.mv V Ham AoomIV AaHoNooV AImHIwV AooH.va mam Ha loom.wm Ham Room.mmV mam maanccm \sAIJI . IvaIounssmnmIoo an x . / 132V ,oon mmVnmIHm IHm.mH.mH.mH.m.I.m. \V 4/ ¢ 0 we Aooa.ImVrmIom H s 4 5 Hoov.onV mam (» 3 Amew.m I Ioom.omV mam HmoImmeV CmfimV I I n \ I \II . 5 mm m A V I “www.mmww WWW mamasccwmvNVOHowsz vm AmV E u .l o . I l I H H on INH mo n a a Aooo.mm V wmm mIInI mH mH I H I ./ I 0 ms 133V m.H I Hoom.mm V mmm _1 / A me AonwcmsHo-IV AwsmuooomHV I mom mZZ .>.D mEmZ mt” musuosnum oHumE I . IOHaflc / i1 MHfl m/Xk: co maco ._ : _I\ .r/: AHIHHHQ ImumcH o A m V nmmmnV H mHS pom mamasccmmomV om . o mammaom m mm mw>m£wn Aooo.vaV wmv m\/fl w“ W : IImHnmImcs nanomsoo 1000.33 V mam : 1. : AodmeHoV 6 3 ma *5) Aoom.mH V Has 1 E . Aooo.mHHH mwm ncmHsccmHomI _ V OI A damn Aoow.mm V oom IOInsnnnHIIIIH.m.H on ncmsHom LIHa manage ocV AOOI.mm V Ham \- Aan 3.0 m I Hooo mm V Imm ”W \\ ImHonoV IIwLInV wwm .mzZ .>.D TEMZ TIFIIII deuUflH-Iwm Oman-ME IOH< ”HmEomH HOV H8 Honda pocV mamasccm : w H H : NWWWMMMW mm 1.3.3333... .. . om Aoom.mm V me flooo.mv V Ion AwsmonoV 7 AHwEOmH HOV MW 3 r r r z AmuHHHQ ImumcH Amnsm uocV mamasccm \ r so >Hco -HomloInsrmnHHI om nmmmnV Ho . o Aooo onV How nooo.hv V omm AmcmeHoV mom mzz .>.D oEmz onsuoSHum oaumE [OMAN mm nI I oa.m I . mm Tmmks Mwmmdw MMM 9.32233: ..H ‘ EV mm.m I . V IoonoHnImH.m.e.HIc>m V + I Iooo 33H mam mm Ameo.m I Iooo.moH mom .I ma II F I s mI \ mH A mHAnemeI3 I HOOI HVnmmHm mcmHsccmHoHVnHran .: m VI mH HmmVAnanm.m I Hoes-oV mwm I®.HIHH.niocmxmn NH m.\- xsz mH AmmyAnHmI.m I Hooo.me-I3m IOHosoHnImchIquoa o mH AmeAeVIH.m I Hoom.mV mmm .1 8 AvHUUV hmcmxwLoHohoV 3 ooT< msoadccm WW mI I omo2 IHoHiquEHIo.H OH AQV mH AmVH.HH I OImI . + ma 1_mm_a.D oEwZ Iotn wHSMUSHum bond .IwHQsoe mHnson u we .ImHnson u a kInHmch u m “Inunmsa n a “InHmHIHss I s .Hnanosm u an “UHumEOHmICOG n D “UHumEOHm H + “UHumCWMEMHmm H m HUHumcmmEMHo I Q .HmcmHmIcoc H dz 5 mm mm.m I AoomIIHV wmm mcmfiscquwHVmflsp ma Asz wI Ioow.oHI vmm IIqumfiImfiuoHIIuv.H o Im.m I Aooo~wHV vow AmoumV MOON§HV mow Mm AoomIm V Ham AOONIm V OIm I Aooo.wme mmm mam scam mxo AQV mm vm.H I ,oom.¢mV mum IIIIImHImHIOMmMW¢.H wH + II I Aoom.wHV mom . 9 mm mm.H I ,oov.I V mmm 3 AOOIII V omm AIHouV AmoumV mm I }\I _ _ Ammflommm z 2 cm / cm mecHH CH GOIOHQ mamasccmflwfiVmwmmuoo ®H “:8 A19 AmV HMHHEHW C‘MLD UHwfluu I'll...” I I I I I I I IOH \fl HQ 7—. Z O mI ImsmIg IIcs.IH)V NH II a w n v m H w n. .\ /\\_ wo.m I : z/%\z AmIoooV I wmm mzz .>.D mEmZ wtfi mnsuosuum oaumE I IOHd I . I _ Im mfi mm.ou I AommIH V can I“ mm mI.o- I AommIm V Imm mcfingom H mH mm.HI I AomIIoH V m.¢vm ImeIUINNIHNIHISIm wH . AQV Hm ma Hm.H- I AoomIoH V mam -mIImIIwHIIHImHINH + mm mv.H- I AoooImmmV m.mwm mH HI.HI I AoooImHmV m.mIm A.D wEmZ mII «usuosHum UHIME I I IOH< \.\I\ an AommIH V mHo Svam VI 93 chmIommxo O a: I AommIv V m.Hmm IIUImNIHNIHILIme wH AQV Hm MI ma.o- I AomemH V m.mmv IIHIwIIIsIoEIwIwHII + mv HI.H- I AoooImme m.mIm pm mwflaoua AoooImmHVsmm.mom Iouwmzflv mm hmwlmmBV A¢mBV mt I mcHLmHOQMHLIIHN 1 Hm mm no.0 I AOImII V m.wIm IHIstIIIIIHImHIw wH AQV 4 mm 00.0 I AoowIm V mwm -HILIIEIIIIwHImHII + mm mo.ou I AoooImIHV oHv AmHoooV A.D mEmZ mkfi musuosnum oaumE I IOH< um wt mm 3V mad I u: um AwVNI.m I nomem V «Hm QIIInmIomamst mm ImeN.m I AoomIm V mam -IIIIwHImHIwIHInImE wH AoV um I AmeH.o I AOHvIw V omm -mIImIIwHINHIIIN II I: + mfi Ava.o I AowHINH V Imw mv Avem.ou I IoomIvaV mom v2 AmaoooV Im an MN Hm.OI V mCHLQHommHLI 9 mt mm «0.0. I AommIm V me -Mmmwmmmmwmwamwmwm wH AmV Q Hm mm mo.ou I AoooIHH V m.IHm . um mm mm.ou I. AoooImomV mam AmaoooV AamEV u: II om l mcflnmnom o: mm «0.0. I IMILIIwummIHNIHIgIon ma AoV mm No.0- I AOIvIv V m.mmm -IHIwIHIsImEIwIwHII Im . + Hm mm mm.oc I AoomIm V m.mmm mm II.0I I AoooImmHV mfiw u AmaoooV A.D mEmZ wIIIII wusuoswum UIIME I ; IOHAII 43 mm .m E Aooonm V mom I: I: mewmw mm 2330355 mm Awva.mH I “oomImm V wow -mHIIIngIwewxwg ma ADV I. I o wm ma ImeH.H I IoooImHHV mam ma II NH m m m z I: + mm Amem.o I AoomIoI V mwm I: 0: AnHoQoV Mm Ame.mH I . wHOHHOUMXO mm o I ma . I I I IA w I V mo.o I Aomv IN V m.mmm IwIIMmIMHmMMWMIm AQV mm AOImIoH V m.ovm + I wm.o I AoHvam V omm mm AmV vm.o I Aomon V m.wwv mm.o I AoooIomHV Ham AIHUQUV AmsflwIIImV I mm.H - mommIIH V m.Hoo mw ImIV AoowIw V Ham mHOIIoomeIc I w.H I IommImm V n.wom IINIHNIIILIIIU IQV mm mH AmVom.o I AoomIoI V m.va INHIwIHIngaIIImHII + mm Amew.o I AoomIIvIV mIm AmHUQUV ,wQHUHHIAmV mmm mzz .>.D mamz qu oIImE ®H5UUUHUW I IOH< 44 flHI N HAmVOO. NI OOHN mH.m I IN 39: gm I MN AU whom” P U HGEOMH | W wmnm W mamasccmHONV mm mN I m.D mEmz mII mHSUUSHIm oaumE IOH< 45 \(2 an oz «m «w .m m m.m I MWMHHMHW m.MMW cflnmgmmmmahsumfimucmm oz 02 Iv . m . OI I . INNINHINIIIININNIII NN AOV ON mN NN O I AONO N V N NIN ImIcmmINNIIHINHININ + mN N.OI I AOONIONNV ONI I: I: Ifimm wumHoHnonm mm .m E ANHUQUV AvOHUm &m. o\wcouwomV mH ON. OH I I IN OI I ON mw NN.OI I I AONNIv V ONO Nv.OI I ,OOIIN V N.N¢O I NI.OI I AOININHV N,NNO OIIIsmmmmmonO MN NN.O I AOHNIHHV N.NNN IIIngEIIIIIHINIIN NN AQV mN IO.OI I AOOOIwNIVN.NNw IHINIIIIIINHINIII + Iamm wumnononm mm ANHUQUV AwOHom Rm.0\®QOIoUmV Mv AmVNh.m I Q HwEOmH m N NI.N I AOOHI «NV NIN ON IN A NNV NO.N I AOON OOV NON mamasccm AONV mv AEVNN.NII.N I AOON NNV smIHN IONcoanINHIIHINII ON O mv AEVNO.NII.N I AOOH N$ NON ImonOIvHIHIIvIH AIOIONEQV ANIomoV wmm mzz .>.D mEmZ mhk musuosupm 0flumE : IOHm 46 )2 fin M¢ AvmmV WWHW w A mamasccm A V IN . w I IAIH OIOIIOIOIIIIIN NN N2 I NO I I AOOI N V NHO I I I I I O m« AOOIV IN.N I AOOOIONV INN aonO II «I O N mN AmVNN.N I AOONIONV OON ANHOOOV AImnImV MM m 2 a I. \waerAWWY/ I v P I O mw 3de mflv I ..xI o a: mH.¢ I I V mamasccm m4 2 IN mv AON.D mEmz mtfi muduUSHum UHumE mm 7 4 mm Amwaommm HmwcHH Ca mcouon HmHHEam mm memV 0. Vin. m I m HmEomHAHmLqu mamasccmaomexoam OOOIO W OOO ImucmszNIONHNN OHO IOHIOHIOHHOHIIIOIH vm vmm ¢ HoEomHAHmLumV ¢.Hlm.H I Ammflowmm Hmmcfla GI wcououm ImHHEHm :mnu AOOOIOH V anIm AOOOIOOHV NOO AOOOI OOHV Own AOONI mm V memm mamasccm AOOOI OH V OON IVONVIxommmIImI m mwmmmmhmfiwmoV:NNIOHIOHIOHHOHIIHOIH AOOOIOOHV OOO AOOOIOOHV Own AOOOIOO V OOONO IOOOIOV N.O-H.O I VOOHINH V OON a HmEOmflfluwnumV MN MO AmVOO.m I AOOOI O V IHO IO mN AmVNO.O I AOOOI OOV OOO mamasccm MO AwmmV OOHO I AOOOI OOV ngON -VNNVOIOIIxomm NN O O O I AOOOI OHV OON -III1IIIOHIHHIOHOIN AOHUQUV Auwnqu wmm mzz .>.D. GEMZ Iwhnn QHDMUSHHM OHWMM .Umscflucoo .HH mHQMH DISCUSSION AND RESULTS 3,4-Dimethylpyrrole, §QJ was chosen as the starting material for the construction of the ring system Z§ because / \ N H §g it possesses only reactive o—positions, thus preventing re— action at the y—position, and it is symmetrical, eliminating structural isomers later in the synthesis. The precursor to §Q was ethyl 3,4—dimethylpyrrole~2—carboxylate, §§x which was prepared according to the procedure of Badger,89 Scheme 1. Na.6 pH Z / \ 09 N n / \ HOAC/H o + g x + £th —-——2—> ,. 5 ~ H H E = "C02CH2CH3 8i ea :22 {51 Scheme 1 The condensation of diethyl 2—aminomalonate, which results from the reduction of fig in gitg, can give either ethyl 3.4—dimethylpyrrole-2—carboxylate, §gfl or ethyl 4,5-dimethyl- pyrrole—Z—carboxylate, §$, depending on whether the 48 49 aldehyde or the ketone group in 3-formyl—butan-2—one, QL, is attacked. Since the aldehyde group is the more reactive, one would expect compound §§ to predominate. Badger reported that §§ was the only product isolated, even though he locked for the 4,5—isomer §4f Upon repeating Badger‘s procedure, this author found, however, that there was approximately 20% of ethyl 4,5—di— methylpyrrole-2—carboxylate along with 80% of §§ in the pro- duct mixture. This was determined by integration of the peak areas of the 3-, 4-, and 5-methyl groups in the NMR Spectrum of the mixture. The 3—methyl appeared at 5 2.28, the 4— methyl at 6 2.01, and the 5—methyl at u 2.21. Recrystalliza- tion of the product mixture from isooctane as reported by Badger afforded a partial separation of the isomers but not a complete one. Pure §§ crystallized out of solution, but upon evaporation of the mother liquor, about one half of the initial amount of material remained. The NMR spectrum of this solid indicated approximately a 60:40 mixture of the 3,4— and the 4,5—isomers still remained. Chromatography of the above mixture using a variety of solvents did not give a satisfactory separation of the two isomers, although with alumina and chloroform a small amount of the 4,5-isomer §g,was isolated and verified by comparison of its melting point with that reported in the literature.90 with this result, it was decided to convert the mixture of pyrrolic esters into a compound which might have properties sufficiently different to affect a separation and yet be 50 convertible back into the pyrrolic esters after separation. It has been reported by several people that halogena— tion of the pyrrole ring can be affected by reaction of pyrrole with halogen, and it has further been shown that the halogenated pyrroles can be reduced to the dehalogenated ring in several ways.91 With this knowledge and the expecta- tion that halogenation might take place preferentially at the more reactive and accessible a—position of §§ rather than at the B—position of §gfl the iodination of the pyrrolic ester mixture was attempted using KI/HZOZ as the iodinating species. Zia; min-In + is). .85: £14. £52 :32 £1 The expected selectivity of reaction and the desired difference in adsorptivities on a chromatographic column were observed. Iodination of the mixture followed by sep- aration on a silicic acid column eluted with benzene gave a 45% yield of ethyl 3,4—dimethyl—5—iodopyrrole—2—carboxylate, fig, as the first fraction off the column. The melting point of 130.5-131.50 is in agreement with the literature value of 133-134°,92 and the infrared spectrum93 also agrees. Dehalogenation of §§ with zinc dust in acetic acid gave gg. A second fraction yielded approximately 100 mg of ethyl 4,5-dimethyl—3—iodopyrrole—Z—carboxylate, fig, as a 51 white crystalline solid whose melting point was 152.5—1550. The NMR of gg shows a quartet (J = 7Hz, 2g) at o 4.37 and a triplet (J = 7Hz, 33) at 6 1.38 correSponding to the ethyl group in the ester, and two singlets, one at o 2.28 (33) and another at 6 2.0 (SE) which correspond to the 5-methyl and 4-methyl respectively. In addition there is a lack of absorption in the region 5 6.5-7.0 where the a- or B-pyr— rolic hydrogens normally appear. The mass Spectrum of fig has a parent peak at 293 corresponding to a C9H12NOZI com- pound. Finally, reduction of fig gave ethyl 4,5—dimethyl- pyrrole—2—carboxylate, Q4” melting point 113—1150 in agree- ment with the literature, 114—1160.90 The third fraction gave 300 mg of ethyl 4,5—dimethyl— pyrrole—Z—carboxylate. Thus the results confirmed the ex- pected selectivity of reaction at the o-position, and the iodinated products did allow a chromatographic separation. Once the preparation and purification of ethyl 3,4—di— methylpyrrole—2—carboxylate, §§J was accomplished, §§ was hydrolyzed and decarboxylated according to the procedure of Badger94 to give a 97% yield of 3,4-dimethylpyrrole, §Qfl and a 5% overall yield from the sodium salt of 3—formyl- butan—2-one, gl. There are several routes for the synthesis of the ring system Z§ from §Q, The first route attempted is that shown in Scheme 2. In the first step, §Q with its two free a— positions would react, possibly by a Michael—type reaction or Grignard reaction,at carbon 1 of a three—carbon unit 52 containing a functional group "X" on the third carbon to give §§x x X R / \ + Greg—('13 ————> N R H 8.9 a 88 Y MI) {.___. a Y 2Q s: Scheme 2 In the second step, §§ with the appropriate functional group "X" could react with an additional two molecules of 80 to give Q?” CompOund §§ in turn would react with a molecule Of §§ to give 20“ a derivative of Z§x 53 Since the pyrrole ring is convertible into a Grignard Species in which the a-position is the nucleOphilic site, "X“ could be either a halogen, tosylate, or a carbonyl group. These would permit carbon-carbon bond formation to take place by nucleophilic substitution in the second step of the sequence. The three-carbon unit chosen to meet the require— ments was 3-butyn-2—one, §Zj it has been shown that the a- position of the pyrrole ring adds across the acetylenic bond95 of 3—butyn-2-one by a Michael reaction to give a monosubsti- tuted pyrrole. Thus, §Z allows attachment of the three- carbon unit to g0; It also was anticipated that §Z might add to both sides of the more nucleophilic dialkylpyrrole, fig, to give a symmetrical tetraalkylpyrrole. In addition to the above features of disubstitution by the triple bond, §Z possesses the necessary electrophilic site (or the source for an alternative reactive site) at the third carbon for reaction with a Grignard species. Treatment of 3,4-dimethyl- pyrrole, §Qfl with two equivalents of §Z,in refluxing methanol for 40 hours gave upon work—up a 54% yield of 2,5—bis(3-oxo— butenyl)—3,4—dimethylpyrrole, 21, as golden crystals melting at 241-2420. The spectral data confirms the structure of 21. o / \ + REC-34 H3 ____9 N H 8.9, :21 54 The N—H hydrogen in g; is rather acidic as a result of the extended conjugation of the ring with the carbonyl groups. Because of this, compound 21 is not suited for re- action with a strong base like the Grignard species. There— fore, 21 was reduced with NaBH4 in methanol to give a cream- colored solid. Its NMR spectrum in DMSO—d6 indicated that the desired reduction product, 22, had been formed: an ABMPS pattern (6 6.38, 6.05, and 4.33; JAB = 15Hz, J = 4H2, J BM AM 3 0, and JMP = 6H2) correSponding to 4g (5 6.38 and 6.05) and 2g (6 4.33) respectively, a doublet at o 4.72 (J = 2Hz, 2g) for the hydroxyl hydrogen, a singlet at a 1.91 (6g) for the 3,4—methyl groups, and a doublet at C 1.2 (Pof'ABMPs, JMP = 6H2, 63) for the terminal methyl groups. Upon treat— ment of this compound with tosyl chloride in pyridine to form 93, only tarry solids were obtained which did not yield any identifiable products. 55 With these negative results for the conversion of gl to 23, attention was directed toward the synthesis of the saturated diketone, 25, If the preparation of 25 could be accomplished, then direct nucleophilic attack on the carbonyl group could take place without the interference of the acidic N—H hydrogen. Treibs has reported the electrophilic substi- tution of acrylic esters on pyrrole and substituted pyrroles catalyzed by boron trifluoride etherate.96 Application of o / \ + H26=CH— N H Q3. 92 25. his procedure to the reaction of methyl vinyl ketone, 24, and §Q gave only a tar. Webb97 was able to substitute pyrrole with 24 under mild acid conditions, and following his procedure with §Q this author obtained again a viscous liquid which could not be purified. Finally, it was found that 2,5—bis(3—oxobutyl)—3,4-dimethylpyrrole, 25/ could be prepared in 87% yield by refluxing §2 and two equivalents of 23 in methanol for 4 hours. Compound 25 is a pale yellow viscous liquid boiling at 135—137°(0.15 mm). All spectral properties agree with the structure of 25. Reaction of 22 with the 3,4—dimethylpyrrole Grignard, 96, gave only an impure solid which was very air senSitive NV 56 and unstable on either silicic acid or alumina columns. Efforts to convert the magnesium alkoxide from the Grignard reaction into the acetate of the alcohol were also unsuccess- ful. It appears that if alcohol 21,i§ formed, it is very unstable. At this point, it did not seem that direct attack on the ketone carbonyl or conversion of that carbonyl to a good leaving group for participation in a nucleophilic substitu— tion reaction was going to lead to success. It was thought that perhaps the reaction of the pyrrolic Grignard on an ester, where the product would be a pyrrolic ketone, might eliminate the experienced difficulties in the previous re— actions. To this end, the sequence of reactions in Scheme 3 was carried out to prepare the diester 102. The reaction of ethyl propiolate, g§fl with §Q in re— fluxing ethanol was tried, using the previous reaction of 3‘bUtyn-2-one, 87, with §Q as an example. A pale yellow Solid melting at 50—51.50 was obtained in 76% yield. The 57 / \ R \ \ on N + Haze—cost —-—-> \ m1 H 80 2;; 99 [H] \\ \\ St 98 o \ NH 5 \\ cm 0- 08+. 101 129. [H] Scheme 3 58 spectral information and C, H analysis indicated that this compound was ethyl 3—(3,4—dimethylpyrrol—2—yl)propenoate, 22. Hydrogenation of 22 at 40—50 psi and room temperature with a Pd/C catalyst gave a quantitative yield of ethyl 3-(3,4- dimethylpyrrol-Z—yl)propanoate, 129/ in agreement with the spectra for 190, It is a pale yellow liquid boiling at 87— 90°(0.2 mm) and is unstable on a silicic acid column. A second molecule of g§ could be substituted on 122 to give ethyl 3-(5-carbethoxyethyl-3,4—dimethylpyrrol-2-yl)- propenoate, 121/ in 47% yield as a pale yellow, waxy, crys- talline solid recrystallizable from pentane and melting at 41.5-43.50. The NMR, IR, mass spectrum, UV and C, H analysis confirmed its structure. Finally, lgl,was reduced to give a quantitative yield of diethyl 3,4—dimethylpyrrole—2,5— dipropanoate, 192” as characterized by its spectral data. Once 102 had been prepared, it was treated with the 3,4—dimethylpyrrole Grignard, QEJ followed by the usual 0E1. 96 19.2, of a white solid was work—up, and a small amount (15%) 59 isolated which was recrystallized from chloroform/pentane and had a melting point of 148—1500. The NMR of the solid was inconsistent with either compound 123 or starting mater— ial, although it did indicate the presence of a free a-pyr- rolic position. The mass of the largest ion in the mass spectrum was 293 rather than the expected parent ion of 393. Upon repeating the reaction three times, no solid product could be isolated. Having had no success with the Grignard approach to the substitution of the two pyrrole rings at the ends of the three—carbon side chains, the author looked at the possible use of the Vilsmeier acylation reaction. Several groups98:99 have demonstrated that pyrrole and various substituted pyr- roles can be acylated in yields of 93% down to less than 5% by the Vilsmeier reaction. In order to utilize the Vils— meier reaction in this synthesis, the N,N-dimethylamide derivative of 102 was prepared. Hydrolysis of 192 gave ap- proximately a 94% yield of the dicarboxylic acid, 104, This green solid was then treated with triethylamine at 0—100 followed by ethyl chloroformate to give the mixed anhydride which was not isolated but reacted immediately with an ex— cess of dimethylamine to give upon work-up a tan solid, recrystallizable from cyclohexane and melting at 101—102°, The NMR for 195 was consistent for N,N,N',N',3,4—hexa— methylpyrrole—Z,5-dipropanamide. 60 104 Mmgh 105 When 195 was treated with phosphorus oxychloride in the usual way9sr99 followed by two equivalents of 3,4—dimethyl- pyrrole, g2” and worked up, no compound corresponding to 123 except a small amount of starting material was isolated after chromatography of the reaction mixture. Similar re— sults were obtained upon repetition of the reaction pro— cedure. Scheme 4 m 62 Since the several attempts to synthesize that portion of compound Z§x which possessed three of the four ”corners" and two of the ”sides" of the 26 w—electron ring, ended in dead ends, a new approach to the synthesis of the macro- cyclic ring was sought. The approach taken was to synthe- size compound 109J Scheme 4 -— a compound which incorporates two “corners“ and one "side" of the macrocycle zg. If com- pound 199 could be made, then reaction of the trialkylpyr- role rings with their free a-positions with §Z should give 129, Once 119 was synthesized, 109 and 112 could undergo the typical condensation reaction of pyrroles with aldehydes or ketones to give a hexahydro~Z§fl 111, Compound 11; could then be dehydrogenated with DDQ or possibly by just bubbling oxygen through a solution of 111 to give the decamethyl derivative of lg, 15%. The synthesis of 109 should be possible by preparing the dipyrryltrimethine salt, 19§u followed by reduction. It has been shown that trisubstituted pyrroles (where one substituent is an ester group) and disubstituted pyrroles (where the substituents are phenyl groups) condense with 1,3—dicarbonyl compounds under acid conditions to give di— pyrryltrimethine salts like lggxloollol This condensation has also been accomplished by LeGoff102 using a trialkyl— pyrrole and 1,1,3,3—tetramethoxypropane, 121” The attempts to react §Q with 191 under hydrogen bromide catalysis proved unsuccessful. The only thing observed was the forma— tion of a deep purple solution and isolation of a small 63 amount of a brownish—red solid which was insoluble in almost all solvents. Extraction in a Soxhlet with methylene chlor- ide gave a purple solution which upon evaporation of solvent gave a deep maroon—colored solid, soluble in chloroform and methylene chloride. The NMR of this solid was incompre- hensible. Upon repeating the reaction with variations in temperature, time of reaction, solvent, and mode of addition, the same results were obtained. Assuming that possibly electrophilic attack on the tri- methine bridge was taking place, a substituted bridging group was considered. This substituted bridging group would have to be a symmetrically—substituted one in order to elim- inate the problems of structural isomers later in the syn— thesis. This could be accomplished by condensing §2 with either cyclohexen—Z—one, 113” or dihydroresorcinol, 114, which would give the dipyrryltrimethine salt, 115. 113 or + / \ N H 0 us S2 115 Treibs103 had shown that reaction of either 113 or 114 with several substituted pyrroles gave (in varying yields) a trimethine salt analogous to 115. These salts all 64 absorbed at approximately 565—590 nm in the visible spectrum. Attempts at reacting llg,With 82 only led to an unpurifiable, deep maroon-colored solid which appeared as a glass on the walls of the flask upon removal of solvent. Synthesis of 115 (X = I) was successful from 114 and 82 according to all information except the NMR. A crystal- line metallic—green solid precipitates out of the red-violet reaction mixture in 30% yield. After filtration, washing with ether, and drying, the compound had a melting point of 248-2500 and had an absorption maximum in the visible range at 575 nm. The absorption maximum of analogous trimethine salts is at ~ 570 nm. The highest mass ion in the mass spectrum of 115 is m/e 266, which is the parent minus HI which is not to be unexpected. The infrared spectrum indi- cates extensive hydrogen bonding of the N—H hydrogens and a conjugated double bond system. The C, H analysis is in good agreement with a C18H23N2I molecular formula for 115; Be~ cause of the low solubility of 112 in the available NMR solvents, a 100 MHz spectrum accumulated on a time—averaging computer (CAT) was run. A satisfactory integration of the CAT spectrum could not be obtained because of a malfunction in the CAT integration capability, and there was too low a Signal-to—noise ratio to allow a good integration of a single Scan. The spectrum from the CAT and the available integra- tion shows a singlet at o 8.4 (IQ) for the vinyl hydrogen, a doublet at 5 7.64 (J = 4H2, 1g) for apparently only one d-pyrrolic hydrogen, a triplet at o 3.1 (J = 7Hz, 4g) for 65 the allylic hydrogens, singlets at 6 2.42 (65) and 2.13 (63) for the 3— and 4—methyls respectively. The two large, broad singlets at 5 1.64 and 1.32 do not fit the structure of 115. These appear to be impurities. The precedence for the reduction of li§,to 116 by catalytic hydrogenation with Pd/C in a Parr hydrogenator is found in the reduction of 117 to 118, 117 125: The NMR of 116 shows a broad singlet at 5 7.63 (23) corresponding to the N-H hydrogens, a poorly—defined doublet at 6 6.43 (23) for the a-pyrrolic hydrogens, a complex multiplet with two well—defined singlets from 6 3.03 to 1.36 (22a) corresponding to the 12 methyl hydrogens, the 8 methylene hydrogens, and the 2 methine hydrogens. From all the spectral data, except some parts of the NMR of 115” and it appears that the structure of the reduction product 116, 112,15 that shown. 66 The next step in the sequence was to react 116 with 87 to give 119. The small amount of available 116 was reacted 116 112 W with 81 and upon workup and chromatography on alumina with 10:2 benzene — methylene chloride, no identifiable product was isolated. Due to the lack of trimethine salt, 115, this reaction was not repeated. The reaction leading to the trimethine salt, 120/ was tried, using ethyl 3—(3,4—dimethylpyrrol-2—yl) propanoate, 129, as the pyrrole source. When 190 and 114 were refluxed for 3 1/2 hours with 51% HI and worked up, a green solid was obtained which was recrystallized from cyclohexane-methanol to give green needles melting at 136—1380. The NMR and the infrared spectra agree with structure 120” The NMR has a singlet at c 8.05 (1H) for the vinyl hydrogen, a quartet at 6 4.13 (J = 7Hz, 4H), and a triplet at 5 1.25 (J = 7Hz, 6H) for the two ester ethyl groups, a complex multiplet at 6 3.4—2.83 (12H) for the side chain methylenes and the \ 0131’. + 0 100 120 allylic hydrogens, and then two singlets, one at 6 2.31 (6H) for the 3,3'—methyls and 5 2.01 (broad, 8H) for the 4,4'- methyls and the symmetrically—located methylene in the six- membered ring. Its UV maximum is at 597 nm. It was with the synthesis of 129 which incorporates two "corners" and three "sides" of the 26—membered ring System that the synthesis of the title compound was termin— ated due to other commitments. However, it is evident from the last few reactions, that the synthetic approach most amenable to the successful synthesis of the title compound Or a derivative is the path utilizing an appropriately sub- Stituted trimethine salt such as 120 or the saturated 68 derivative, 116] for the cyclization to the 26-membered ring. This cyclization step will probably be the poorest step in the sequence because of the large distances between the reacting ends of the linear tetrapyrrolic species. But if the reaction is done under high dilution, a respectable yield should result without much polymerization. The final step involving oxidation to give the completely conjugated system should be a facile one. It has been observed in the porphyrin syntheses from bilanes that the oxidation which gives the porphyrin ring is accomplfimed by aeration of the reaction mixture.104 Future work should include the preparation of 119 and then condensation of it with 116. Also the condensation of 129,With 116 should be attempted. If an alternative to these two sequences is needed, then preparation of some other appropriately substituted trimethine salt ought to be investigated. EXPERIMENTAL General Procedure The melting points were determined on a Thomas Hoover Uni—melt melting point apparatus and are uncorrected. The infrared Spectra were recorded on a Perkin-Elmer Model 237B Spectrophotometer. The NMR spectra were obtained on a Varian T-60 and HA-lOO spectrometer with chemical shifts reported in é—units measured from tetramethylsilane as the internal standard. The UV spectra were recorded using a Unicam Model SP-800 spectrophotometer using 1 cm quartz cells. Mass Spectra were obtained with a Hitachi Perkin—Elmer RMU—6 mass spectrometer. Microanalyses were performed by Spang Microanalytical Laboratory, Ann Arbor, Michigan. Eghyl 3,4—dimethylpyrrole—2—carboxylate (§3) and Ethyl 4,5- dimethylpyrrole-2—carboxylate (84) A solution of 142,5 g (2.06 mole ) of sodium nitrite in 210 ml of water was added dropwise over a 20 hour period (Slowly enough to prevent evolution of nitrogen oxide gases) to a vigorously stirred solution of 120 g (0.75 mole) of diethyl malonate in 130 ml of glacial acetic acid. After 20 hours the solution was added to a separatory funnel and 69 70 allowed to separate into a lower aqueous layer and an upper organic layer for 3 hours. The layers were separated and the organic layer was added to a solution of 70 g (0.574 mole) of the sodium salt of 3-formylbutan—2-one in 250 ml of glacial acetic acid and 100 ml of water which was than heated to 95°. Upon reaching 950, 75 g (1.15 mole) of zinc dust was added at such a rate as to maintain the temperature between 95-1050. When all the zinc had been added, the mix- ture was heated at 100—1050 for one hour. The mixture was then slowly poured into approximately 2 liters of ice—water and chilled in the refrigerator overnight. The orange solid that precipitated was filtered, washed with water, and dried lg zggug over P205. The dry solid was sublimed at 780 (1 mm) to give approximately 9 g (10%) of a cream-colored solid melting at 84-900. This solid was purified by recrystalliza— tion from isooctane yielding white needles of ethyl 3,4—di— methylpyrrole-2—carboxylatez mp 91—930 (lit. value 93°).89 Some of the sublimed material was chromatographed on alumina with chloroform giving ethyl 3,4—dimethylpyrrole—2— carboxylate as the first fraction. A second fraction pro- vided a small amount of a cream-colored solid with mp 113— 1150. The melting point and infrared spectrum are identical With the literature for ethyl 4,5~dimethyl—pyrrole—2—carbox— ylate.90 The NMR spectrum of the sublimed material from Subsequent runs indicated approximately 20% of the product mixture was the 4,5 isomer. 71 Ethyl 3,4-dimethylpyrrole-Z-carboxylate —— mp 91—930; ir (CHCls) 3440 and 3275 cm‘1 (N—H), 2950, 2900, and 2840 "1 cm (C-H), 1670 cm_1 (c=o), 1575 cm—1 (C=C), and 1260, 1140 cm_1 (c—o): nmr (CDCla) 6 6.7 (d, J = 2H2, 13, a-H), 0 4.35 (q, J = 7Hz, 23, -0—c32033), a 2.28 (s, 33, 3-c33), 0 2.01 (s, 33, 4—CH3), and 0 1.35 (t, J = 7Hz, 33, —0—CH2c33). Ethyl 4,5-dimethylpyrrole-2-carboxylate —— mp 113—115°; —1 ir (c3013) 3440 and 3280 cm (N-H), 2960, 2900, and 2840 cm_1 (C-H), 1675 cm“1 (c=o), 1575 cm.1 (c=c), and 1225 cm -1 (c-o); nmr (c0c13) 5 6.72 (s, 13, B-H), 5 4.32 (q, J = 7Hz, 23, -O-C§2CH3), a 2.21 (s, 33, 5—c33), 0 2.01 (s, 33, 4—CH3), a 1.33 (t, J = 7Hz, 33, —o-CH2—c33). Sgpgration of ethyl 3, 4- -dimethylpyrrole-2— carboxylate (83) and ethyl 4, 5-dimethylpyrrole324carboxylate (847 ethyl 3, 4—dimethyl— —5— —iodopyrrole-2—carboxylate (85) and ethyl 4, 5-dimethyl—3—iodopyrrole-24carboxylate (86) To a solution of 17.0 g (102 mmole) of the pyrrolic ester mixture (33) and (33) recovered after recrystalliza— tion from isooctane, 6 g (100 mmole) acetic acid, and 11.4 g (100 mmole) of 30% H202 in 150 ml of ethanol at 80° was added drOpwise a solution of 17 g (100 mmole) potassium iodide in 75 ml of water. The solution was heated at 80° overnight, at which time the red color of the iodine had disappeared. The solution was cooled and crystallized in the refrigerator. A cream—colored solid (15.4 g) was col— lected upon filtration. The filtrant was diluted with its volume of water and again cooled. An additional 4 g was 72 obtained. The crystals were dried over P205 ;£_y§ggg. One gram of the dried material was chromatographed on silicic acid with benzene. The first fraction gave 800 mg of a white crystalline solid whose melting point corresponds to the literature value for ethyl 3,4-dimethyl-5—iodopyrrole—2— carboxylate: mp 130.5—131.5° (lit. value 133—1340);92 ir (CHC13) 3440 and 3225 cm—1 (N-H), 2975 and 2900 cm"1 (C-H), 1 ._ —1 1710, 1690, 1680 cm (c=0), 1560 cm (c=c), 1225 and 1140 cm_1 (c-o); nmr (CD013) 5 4.37 (q, J = 7Hz, 23, —o—c32-CH3), 0 2.3 (s, 33, 3—c33), 0 1.97 (s, 33, 4-033), 5 1.35 (t, J = 7Hz, 33, —O-CHZC§3); mass spectrum (70 eV) m/e 293 (parent). 3333. Calc'd for C9H12N02I: c, 36.89; H, 4.13, Found : C, 36.81: H, 4.12. The second fraction gave 100 mg of a white crystalline solid which is ethyl 4,5—dimethyl—3—iodopyrrole—2—carboxylate: mp 152.5—1550; ir (CHCl3) 3440 and 3275 cm"1 (N-H), 2950, 1 2900, and 2850 cm* (C-H), 1700, 1680 Sh, 1660 cm—1 (c=o), 1565 cm“1 (c=c), 1240 cm‘1 (C-O); nmr (CDCl3) 0 4.37 (q, J = 7Hz, 23, —o—C3ZCH3), 5 2.28 (s, 33, 5—CH3), 5 2.0 (s, 33, 4-CH3), 0 1.38 (t, J = 7Hz, 33, -o—CH2033); mass spec— trum (70 ev) m/e 293 (parent). 333;, Calc'd for C9H12NOZI: c, 36.89; H, 4.13; 1, 43.32. Found : C, 36.81; H, 4.03; I, 43.28. The third fraction gave 300 mg of ethyl 4,5-dimethyl- pyrrole—2—carboxylate. 73 ReductiOn of ethyl 3,4—dimethyl—5—iodopyrrole—2-carboxylate (85) and ethyl 4,5-dimethyl—3—iodopyrrole—2-carboxy- late (3Q) to ethyl 3,4-dimethylpyrrole—2—carboxylate (3A) and ethyl 4,5-dimethylpyrrole—2—carboxylate (33) To a solution of 300 mg (1.02 mmole) of the corresponding iodopyrrole in 5 ml of acetic acid heated to reflux was added in small portions 268 mg (4.1 mmole) of zinc dust. The mix- ture was refluxed for 30 minutes after addition of the zinc, cooled, and poured into 50 ml of water. The precipitated solid was filtered, washed with water, and dried. Recrystal- lization from ethanol gave 152 mg (90%) of the respective dehalogenated pyrrole identified by its melting point and NMR spectrum. 2,5—Bis(3—oxobutenyl)—3,4—dimethylpyrrole (3;) A mixture of 3.5 g (36.9 mmole) of 3,4—dimethylpyrrole and 5.1 g (75 mmole) of 3—butyn-2—one in 125 ml of oxygen— purged methanol was refluxed in a nitrogen atmOSphere for 40 hours. Precipitation of the diketone began after approxi— mately 5 hours. The mixture was cooled in an ice-bath and the solid filtered. The golden crystalline material was recrystallized from 95% ethanol to yield 4.6 g (54%) of product: mp 241—2420; ir (KBr) 3300 cm‘1 (N—H), 2900 cm‘1 (C-H), 1575 cm'1 (c=o, and 1630, 1615, and 1580 cm"1 (c=c); nmr ((CF3)2CO-1.5 320) 5 7.71 and 6.55 (ABq, J = 16Hz, 43, vinyl hydrogens), 0 2.46 (s, 63, -CH3 6 to c=o), and 0 2.18 (s, 63, 3,4-CH3'S): uv max (CHCla) 283 (11,700), 317 (6350), and 425 (23,500); mass Spectrum (70 eV) m/e 231 (parent). 74 Anal. Calc'd for C14H17N02: C, 72.79; H, 7.42. Found : C, 72.83; H, 7.42. 2,5—Bis(3—hydroxybutenyl)—3,4—dimethylpyrrole (33) Tozafiirred solution of 0.25 g (8.06 mmole) of 2,5-bis- (3—oxobutenyl)—3,4—dimethylpyrrole in 25 ml of methanol cooled at 10° was added in small portions a two—fold excess of NaBH4, allowing consumption of the portion before further addition. The initially orange solution changed to a pale yellow color indicating that reduction had taken place. The mixture was poured into cold water and the product was ex— tracted with ether. The ether layer was separated and dried over K2C03. The ether was removed and the resulting yellow oil was dissolved in a minimum amount of chloroform, and pentane was added until turbidity. The solution was cooled and the solid filtered, washed with pentane, and then the cream—colored solid was dried in a drying pistol. The com— pound turns green upon exposure to air and silicic acid and alumina columns. The NMR Shows an ABMP3 pattern (0 6.38, 6.05, and 4.33; J = 15Hz, J = 4H2, J 2 O, and J = AB BM AM MP 6H2), corresponding to 43_(6 6.38 and 6.05) and 23 (0 4.33) respectively, a doublet at 0 4.72 (J = 2H2, 23) for the hydroxyl hydrogen, a singlet at 0 1.91 (63) for the 3,4- methyl groups, and a doublet at 0 1.2 G of ABMP3, J : 6H2, MP 63) for the terminal methyl groups; ir (KBr) 3300 cm-1 broad (N—H, O-H), 2950, 2900, and 2840 cm‘1 (C—H), 1700 and 1570 cm‘1 (c=c). 75 2,5-Bis(3—oxobutyl)—3,4—dimethylpyrrole (23). Two grams (21.05 mmole) of 3,4-dimethylpyrrole, 3.242 g (46.31 mmole) of methyl vinyl ketone, and a trace of hydro— quinone were dissolved in 75 ml of methanol which had been purged of oxygen in a flask equipped with a reflux condensor, nitrogen bubbler, and a magnetic stirrer. The mixture was refluxed under a nitrogen atmosphere for 4 hours. The methanol was then removed on a rotary evaporator and the oily residue was distilled under vacuum to yield 4.3 g (87%) of a yellow oil: bp 135—370 (0.15 mm); ir (liquid film) 3375 cm—1 1 1 (N-H), 2940, 2900, 2850 cm‘ (C-H), 1720 cm" (c=o), 1620 cm‘1 (c=C); nmr (CDcla) 5 8.23 (s, 13, N53), 5 2.71 (s, 83, methylenes), 0 2.13 (s, 63, 3,4-CH3'S), 0 1.9 (s, 63, CH3 a tO C=O); mass spectrum (70 eV) m/e 235 (parent). 333;. Calc'd for C14H21NOZ: C, 71.55; H, 9.01. Found : C, 70.15; H, 8.68. Ethyl 3—(3,4—dimethylpyrrol—2~yl)proypenoate (32) Three grams (31.5 mmole) of 3,4—dimethylpyrrole and 4.5 g (46 mmole) of ethyl propiolate were added to 50 ml of oxygen—purged dry ethanol and refluxed under a nitrogen atmosphere for 15 hours. After removal of ethanol on a rotary evaporator, the yellow residue was chromatographed on alumina with 10:3 carbon tetrachloride-methylene chloride. The first fraction yielded 4.62 g (76%) of a pale yellow solid. This solid was sublimed at 40—450 (0.2 mm): 76 mp 50-51.5°; ir (CHCl3) 3260 cm—1 (N-H), 3025 cm"1 (olefinic 1 C—H), 2975, 2905, and 2850 cm” (C-H), 1675 cm"1 (c=o), 1590 —1 1 (c=c), and 1160 cm (c—o); nmr (CDC13) 0 6.8 and 1550 cm— and 5.47 (ABq, J = 1232, 23, vinyl hydrogens), 5 6.76 (d, 13, q-pyrrolic hydrogens), 0 4.2 (q, J = 7Hz, 23, -O-C32CH3), 5 2.11 (s, 33, 3—c33), 5 2.03 (s, 33, 4-CH3), and 5 1.3 (t, J = 7Hz, 33, -0-c32c33); uv (95% EtOH) 206 (11,980, 287 (3467), 349 (22,300); mass spectrum (70 ev) m/e 193 (parent). 3333. Calc'd for C11H15N02: c, 68.45; H, 7.83. Found : C, 68.45; H, 7.87. Ethyl 3—(3,4—dimethylpyrrol—23yl) propanoate (100). A solution of 1.0 g (5.18 mmole) of ethyl 3-(3,4—di— methylpyrrol—Z-yl)propenoate in 200 ml of 95% ethanol con— taining 0.3 g Pd/C was hydrogenated at 40-50 psi for 60 minutes at room temperature on a Parr hydrogenator. After filtration of the catalyst and removal of solvent on a rotary evaporator, a pale yellow liquid was obtained. This was distilled at 87-90° (0.2 mm) to give almost a quantita- tive yield of the desired product. The pyrrolic ester was unstable on a silicic acid column. Ir (liquid film) 3375 1 1 cm‘1 (N-H), 2975, 2940, 2900, and 2850 cm‘ (c—H), 1720 cm“ (c=o), 1595 cm‘1 (c=c), 1210 and 1180 cm-1 (C—O); nmr (CDCla) 5 8.16 (d, J = 2Hz, 13, N-H), 5 6.36 (d, J = 132, 13, q- pyrrolic hydrogen), 0 4.15 (q, J = 7Hz, 23, -O-C32CH3), 0 2.66 (A2B2 multiplet, 43, methylenes), 0 2.0 (s, 33, 4-CH3), 77 0 1.93 (s, 33, 3-CH3), and 5 1.2 (t, J - 7Hz, 3g, -o-CH2cg3); mass spectrum (70 eV) m/e 195 (parent). final. Calc'd for C11H17N02: C, 67.75; H, 8.79. Found : C, 67.81; H, 8.77. Ethyl 3-(5—carbethoxyethyl-3,4-dimethylpyrrol—2—yl)- propenoate (191). A solution of 3.9 g (20 mmole) of ethyl 3-(3,4—dimethyl— pyrrol—2-yl)propanoate and 2.94 g (30 mmole) of ethyl propiolate in 50 ml of oxygen-purged ethanol was refluxed under a nitrogen atmOSphere for 4 hours. The orange solu— tion that resulted was concentrated on a rotary evaporator and the residue chromatographed on alumina with 5:6 benzene— methylene chloride. The first fraction gave 2.74 g (47%) of a pale yellow, waxy solid which was recrystallized from pentane to yield pale yellow needles: mp 41.5—43.50; ir (CHC13) 3240 cm-1 (N-H), 2960, 2900, and 2840 cm"1 (C-H), 1 1720 and 1670 cm_1 (c=o), 1580 and 1550 cm“ (c=c), and 1160 cm‘1 (c—o); nmr (CDCls) 5 6.73 and 5.37 (ABq, J - 12Hz, 25, vinyl hydrogens), 0 4.2 (q, J - 7Hz, 23, -O-C§I_2CH3 on unsaturated ester), 0 4.16 (q, J = 7Hz, 25, —O-C§2CH3 on saturated ester), 0 2.77 (A2B2 multiplet, 4g, methylenes), c 2.05 (s, 35, 4—CH3), o 1.95 (5,311, 3—CH3), 0 1.28 (t, J = 7Hz, 3H, -O—CH2C§3 on unsaturated ester), and 3 1.23 (t, J = 7 HZ. 3H, —O—CH2C§3 on saturated ester; uv (95% EtOH) 202 (12,260), 292 (2420), 356 (21,900); mass spectrum (70 ev) m/e 293 (parent). 78 Anal. Calc'd for C16H23NO4: C, 65.58; H, 7.91. Found : C, 65.41; H, 7.83. Diethyl 3,4—dimethylpyrrole—2,5—dipropanoate (102) One gram (3.51 mmole) of ethyl 3—(5—carbethoxyethyl- 3,4—dimethylpyrrol—2-yl)propenoate was dissolved in 200 ml of 95% ethanol and 0.3 g Pd/C added. The mixture was hydrogenated at 40—50 psi for 60 minutes at room temperature on a Parr hydrogenator. After filtration of the catalyst and removal of solvent on a rotary evaporator, a yellow liquid remained. This was distilled at 144—1450 (0.2 mm) to yield almost a quantitative amount of the desired reduc— tion product. The compound was slightly air sensitive, turning an orange—yellow. Ir (CHC13) 3410 cm-1 (N—H), 3015 cm‘1 (olefinic C-H), 2960, 2900, and 2840 cm"1 (C-H), 1720 and 1675 cm“1 (c=o), 1600 and 1580 sh cm‘1 (c=c), and 1240 and 1160 cm"1 (c—o); nmr (CDc13) e 8.38 (s, 15, N-g), c 4.2 (q, J = 7Hz, 4g, -O-C§2CH3), o 2.67 (A282 multiplet, 8g, methylenes), c 1.95 (5, 6g] 3,4-CH3'S), and 5 1.28 (t, J = 7Hz, 65, -O-CHzcg3); mass spectrum (70 eV) m/e 295 (parent. Agal. Calc'd for C16H25NO4: C, 65.14; H, 8.54. Found : C, 65.03; H, 8.51. N,N,N',N',3,4—hexamethylpyrrole—2,5-dipropanamide (125) A solution of 0.5 g (1.7 mmole) of diethyl 3,4-dimethyl- pyrrole—2,5—dipropanoate, 10 ml ethanol, and 15 ml of 5% aqueous KOH was refluxed for 5 hours. The ethanol was 79 removed on a rotary evaporator and the aqueous solution acidified to pH 5 with ZMIHCl. The aqueous solution was extracted with ether and dried over Na2804. Upon removal of the ether, a green solid was obtained. An aqueous solu— tion of this solid was acidic and the NMR of the solid showed: 0 8.43 (s, 13, N—E), 0 2.68 (A232 multiplet, 8g, methylene hydrogens), and 5 1.9 (s, 6g, 3,4-CH3'S), con- sistent with 3,4-dimethylpyrrole—2,5—dipropanoic acid (104) Approximately 0.5 g (2.09 mmole) of the above acid was dissolved in 15 ml of chloroform and cooled to 0-100. To this stirred solution was added 0.4 g (3.9 mmole) of tri— ethylamine followed by 0.5 g (4.6 mmole) of ethyl chloro— formate and then stirred for 15—20 minutes at 0—100. The solution was saturated with excess dimethylamine at 0—100 and then stirred at this temperature for 15 minutes followed by 30 minutes at room temperature. The chloroform solution was washed twice with 10% aqueous NaZCO3 solution and then dried over Na2S04. The chloroform was removed and the brownish solid recrystallized from cyclohexane giving 0.5 g (96%) of a tan—colored crystalline solid: mp 101-102°; nmr (CDC13) 5 2.97 (s, 12g, all N—cgs), L 2.77 (A2132 multiplet, 83, methylene hydrogens), and 0 1.93 (s, 63, 3,4-CH3'S). Attempted synthesis of 3,4,3',4'—tetramethyl-dipyrryl- (2,2')-hexacyclotrimethine bromide (198) To a solution of 0.2 g (2.1 mmole) of 3,4-dimethyl— o pyrrole and 0.3 ml of 50% HBr in 4 ml ethanol heated at 50 was added dropwise 0.1 g (1.05 mmole) of cyclohexenone. The 80 solution slowly turned blue. The heat was removed and the mixture stirred for 6 hours. The solid which had formed was filtered and washed with 1:1 ethanol-water. A deep maroon, insoluble, rubbery solid remained. The blue fil— trant was evaporated to give a red-violet solid as a film on the flask. The solid was extracted with methylene chlor— ide (Soxhlet) giving a red—violet solution. Removal of the solvent gave a red—violet solid as a film on the flask. The NMR indicated impure material. Purification of this solid could not be accomplished. 3,4,3',4'-Tetramethyl—dipyrryl-(2,2')-hexacyclotrimethine iodide (115) A mixture of 0.25 g (2.63 mmole) of 3,4—dimethylpyrrole, 0.1467 g (1.31 mmole) of dihydroresorcinol, and 0.6 g (2.39 mmole) of 51% HI in 7 ml of ethanol was heated at 92° for 2 hours. The solution turned from a yellow to a red—violet color. The solution was cooled in the freezer for 5 hours and then filtered. The deep metallic green crystals were washed repeatedly with ether to yield, upon drying in a drying pistol over P205, 162 mg (30%) Of product recrystal- lizable from methanol: mp 248-500; ir (CHCl3) 3150 cm—1 (N—H), 2900 cm—1 (C—H), 1600, 1555, and 1520 cm-1 (CZC); nmr (CDCla) 5 8.4 (8, lg, vinyl hydrogen), 0 7.64 (d, J = 4H2, lfl, a-pyrrolic hydrogen), 0 3.1 (t, 4H, allylic hydrogens), 0 2.42 (5, 6g, 4,4'—methyls), and c 2.13 (s, 6H, 3,3'- methyls) uv (CHcls) 282 sh (4140), 291 (8270), 368 (2960), o I 81 538 sh (14,200), and 575 (88,600); mass spectrum (70 ev) m/e 266 (parent - HI). Anal. Calc'd for C18H23N2I: C, 54.87; H, 5.88. Found : C, 54.88; H, 5.82. 1,3-Bis(3,5—dimethyl-4-ethylpyrrol-2—yl)propane (118) A solution of 0.363 g (1.0 mmole) of bis—2—(3,5-di- methyl-4—ethylpyrrole)trimethine bromide (111) and 0.136 g (1.0 mmole) of sodium acetate in 100 ml of 95% ethanol con— taining 0.1 g Pd/C was hydrogenated at 40—50 psi for 3 hours at room temperature on a Parr hydrogenator. The solution was filtered through K2C03 and the ethanol removed on a rotary evaporator. The residue was dissolved in ether and filtered to remove sodium acetate. Upon removal of the ether, a greenish viscous oil remained. After further removal of solvent at 0.2 mm Hg pressure, the viscous liquid gave an NMR spectrum devoid of olefinic hydrogens and the appearance of additional alkyl hydrogens. NMR (CDCl3) 0 7.1 (s, 23, N—H), 5 2.8 - 1.5 (complex multiplet), 5 2.08 (s, 5—cga), O 1.95 (s, 3-CH_3), and 5 1.07 (t, J = 8Hz, 65, —CHzcg3). Peaks between 0 2.8 - 1.5 correSpond to 223. 1,3-Bis 3,4-dimethylpyrrol—2—yl)cyclohexane (116) A solution of 100 mg (0.5 mmole) of the correSponding trimethine iodide and 150 mg (1.83 mmole) of sodium acetate in 100 ml of ethanol containing 0.1 g Pd/C was hydrogenated at 40—50 psi at room temperature for 2 hours in a Parr 82 hydrogenator. After filtration of the catalyst over K2C03, the solvent was removed on a rotary evaporator. The residue was dissolved in a water-ether mixture and the ether separ— ated and dried over K2C03. Upon removal of the ether, a yellowish—orange viscous liquid was obtained. Any residual solvent was removed under 0.2 mm Hg pressure. The liquid was very air sensitive, turning green in the air. It was distilled at 185—1900 (0.18 mm) to give a glassy syrup. The NMR spectrum indicates that the liquid is the desired pro- duct: nmr (CDCla) 5 7.6 (s, 25, N—_I-_I_), 5 6.43 (d, J =- 2.5Hz, 2H, a—pyrrolic hydrogens), 0 3.47 — 1.2 (complex multiplet), 0 2.03 (s), 0 2.00 (5). Peaks between ) 3.47 — 1.2 cor— respond to 22H. Reaction of 1,3—bis(3,4-dimethylpyrrol-2—yl)Cyclohexane (116) with 3-butyn—2—one (81), the attempted synthesis of Egg A solution of ~ 0.5 mmole of 116 and 103 mg (1.5 mmole) of 3—butyn—2—one in 7 ml of methanol was refluxed for 4 hours. The solvent was then removed and the reddish—brown viscous liquid was chromatographed on alumina with 10:2 benzene-methylene chloride. No identifiable product could, be isolated. 5,5'-Bis(carbethoxyethyl)—3,4,3',4'—tetramethyl-dipyrryl- (2,2')-hexacyclotrimethine iodide 120 A mixture of 0.5 g (2.56 mmole) of ethyl 3-(3,4—di— methylpyrrol-Z—yl)propanoate, 0.1434 g (1.28 mmole) of di- hydroresorcinol, and 0.6 g (N 2.25 mmole) of 51% HI in 7 ml 83 of ethanol was heated at 60-800 for 3 1/2 hours. The solu- tion turned from a yellow to a deep blue color. The mixture was cooled in the refrigerator and then filtered to give a mat of green crystals. This solid was recrystallized from cyclohexane-methanol to give green needles: mp 136—1380; ir (CHCla) 3150 cm"1 (N—H), 2925 cm'1 (C-H), 1720 cm"1 (c=o), 1 1 1610, 1550, 1500 om‘ (c=c), and 1290 om‘ (c—o); nmr (CDCla) 5 8.05 (s, 13, vinyl hydrogen), 5 4.13 (q, 43, -o—cg2CH3), 0 3.4—2.83 (complex multiplet, 12H, methylenes in side chain, and allylic hydrogens), 0 2.31 (s, 6H, 3,3'-methyls), 0 2.01 (s, 8H, methylene in six—member ring and 4,4'—methyls), and 0 1.25 (t, 6H, —O-CH2CH3); uv maximum (CHC13) 597, 552 sh, 375, 297, and 282 sh. APPENDIX 84 . MICRCNS 5'0 '0 8.0 TRANSAU {TANCE ()3; 2500 2000 FREQU£NCV CM' 5.0 ' oio 7.0 80 M'CRONS 10.0 11.0 121.0 15.0 A I I .l A ‘ l ‘ A I I | I I I I I | ‘ I ‘ 4 ‘00 ,' “"1""' ‘ g 7"“r"‘f : E ’7‘77"j"‘~- -'; "“2 -; , --j 100 80 550 z < E z "240 ._ at L! r- 20 " "“"'. ' ‘ ':" .' ';" ' "i‘ V‘ . i a i ' - E | ' (:1—-——. 5 I ' : ' , . . ____ 0 2000 1800 1600 1400 1200 1000 800 fREOUENCV (CM'1 Figure 3. Infrared spectrum of ethyl 3,4—dimethylpyrrole— 2-carboxy1ate, 8’11 (CHCla). 7.5 3.0 3.5 40 M'CRONS 5.0 5.0 8.0 -... _ ’ l I l J l l l l l ' l 1 ' 1 ' ‘ 1 100T .. .. ,. i . M100 1 1 80 80 350 60 Z '4 z: .5, 240 40 < C! )— 20 , 20 0 1‘ ' ' ' i ‘ 0 4000 3500 3000 2500 2000 1500 FREQUENCY 'CM' =0 ' 5.0 7.0 80 WOW“ 10.0 11.0120 15.0 -.__ i.‘.1....l.. 1-..].1....1.1 '.‘ l0!) 1 .-- .... -....- .._.- .... 3 I . . . I . ‘ .; ;. . ' . .1. ' . ... ; ' 1 - — -s - - 1 1 : é 30' , j 1 - ' 1 .1 | Z . 1 < - 1 E .. .1... 2 1 “2' 10 ' < 1 E .1.-. _. ..-. ' : l _ 1 § 20 ——(~- ~ 1r —- , ...: 2o . i : 1 ' , 1 1 . 1 i "‘5‘ i "1 ' 1 . , . 1 1 1 ‘ 1 1 0 -__ - 1 - 1 , 1 . . -_ 0 201:0 1800 1500 1400 1200 1000 800 FREQUENCY [CM ‘) Figure 4. Infrared spectrum of ethyl 4,5—dimethylpyrrole— 2—carboxylate, 8’4] (CHC13). 4‘) HECTOIIS 5“ ()0 8.0 TRANSMITTANCE(°/b) 2500 2000 _ 1500 'P‘U'ilrll V U M 1 111.... 5.0 ' 5.0 7.0 80 M'CRONS 10.0 11.0 12.0 15.0 1 . . 1. ...1...1 »1114L.1'1 ___. so”... . - 1 I 60 o o 1 TRANSMITTANCE 1;; b O " ii 1 1 1 1 ' . 1 1 .1 3‘: ; 3' 1 .1 i 1 1 20 »- -44 i -1. 1 0 1 , - t 1 . - 2000 1800 1600 1400 1200 1000 800 moumcv (CM '1 Infrared spectrum of ethyl 3,4—dimethy1-5—iodo- Figure 5. pyrrole—Z—carboxylate, §§,(CHC13). 3.0 21.5 4.11 “@0115 50 6.0 8.0 'l l . .. ..‘. . . ' . .. . . . ... . ’3 ‘3', W U z < .— ’2 2 U) z < M 5.. _L___ 2500 2000 "‘lOUlHl V (M v 5.0 710 80 M'CRON5 10.0 11.0120 16.0 1 1 .1 .Llrilrr 41.11 J 100 -: 1 ‘ I 1 2 e ! i 1 ; : 1 I 1 : . 1 1 i ' i 80 3 ' 1 560 z < H , ...... ’: E t£40 — < ‘ 2 C2 1 : 1‘ : z i 1 . 20 ll . _ i' 1* 1 0 ‘ > ' 0 2000 1800 1600 1400 1200 1000 800 FREQUENCY 1CM'1 Figure 6. Infrared spectrum of ethyl 4,5—dimethyl—3-iodo- pyrrole-Z-carboxylate, fig (CHC13). 88 1 100 80 .‘\ TRANSMHTANCEfL; 2500 2000 "(QUINCY (CM'1 5.0 7.0 8.0 M'CRONS 10.0 11012.0 16.0 1.. n 1 1 1 1 1 1 1 ' 1 1 1 1 1 1 l 1 100.1..' .-.- .:. .:. . ..: 100 80 ~—- 360 1 - E I j a «—+— — Z . 34o __- < M .— 20 ‘2“‘— "§ . i 1 2" i i 9 ‘ . " I L ‘ 1 ' 3 2000 1800 1400 1200 100 800 FREQUENCY (CM') Figure 7. Infrared spectrum of 2,5-bis(3—oxobutenyl)-3,4— dimethylpyrrole, 2; (KBr). 89 l" 3.0 315 4,0 Inmnuwo 5.0 6.0 0.0 -_ 1 1 1 1 1 1 1 1 L I : , - ,1: 1 00‘ ’ I J ' ' ~ 1 -- 100 ' 80 60 40 20 1 20 1 1 ‘ 1 1 ‘ ‘ ' - 1 1 1 1 ; 1 1 1 (1000—m 3500 3000 2500 2000 1500 50:001.ch (MI 6.0 7.0 8.0 "WWW 10.0 11.0 12.0 16.0 “““w' “"*‘_1__'_._.:::_:1::—:'___-.r.__ "T‘T‘Tf‘f" _ ._100 00 _ ....-.Tri‘j. -__ _*“—“1 ““1 so 80 ' H : 60 60 ' '1 40 .40 - 1 1 20 20 ' -.1 | J I . 1 1 ‘ ___1__.;:_.;__;--.__;___.1-__.L_ - .__.______.1:____.;.______O_o._._. .. _- 0 20000 . fl 1300 1600 1400 1200 1000 8 “(outrun {54‘ Figure 8. Infrared spectrum of 2,5—bis(3—hydroxybutenyl)- 3,4—dimethylpyrrole, 2’2" (KBr). 90 MICRONS TRANSMITTANCE 17.1) .1.-. 2500 2000 'REQUENCV ICM '1 5.0 8.0 1111:010le 10.0 11.0 12.0 16.0 1 1 1 1 1 1 A 1 1 1 1 1 1 1 100 ‘ - - »-—-— i '__i- -.-._ - 1- _ 2|"; (:1 “1 s: 1‘°° I 1 1 1 1 80 0 O A O TRANSMITTANCE .,:. 2O _____.__i|_'____ . - - o 2%00 1800 1600 1400 1200 1000 800 FI‘QUINCV (CM'I Figure 9. Infrared spectrum of 2,5—bis(3—oxobutyl)—3,4— dimethylpyrrole, 2,5" (liquid film). 2< ' 3.0 35 4.0 'M'CRONS 5.0 6.0 8.0 ' 1 I l I I J 1 1 L ' ‘ ‘1 ' ___ 100 . . --7 - _. 1 ‘ I 1 : 1"" --.. ”.421- .. . 1 V . 2 . 1 . W100 1,: 1 1' 1 1 . 1 .' . 1 1 — ; 2 1-——A2«—— -1- - - : - 1 1 I 80"——'v\/F .11. 1 - 1 80 60 20 40000 1 __ 3500 3000 2500 2000 1500 FREQUENHV CM‘ 5.0 6.0 7.0 80 M'CRONS 10.0 11.0120 16.0 1 .1 1 111‘1‘1‘ 1111111,.1 1.11114? ' ‘00 ‘ *1"? "‘1 ' 1 l “ 1 5 1 ; ; .1 ( 1 1 . 1 1 f i 3 1 1 I ,1 I I 1 ‘ 1 1 380 1 \11; 1 _i 60 O O TRANSMITTANCE 5 O 20 40 20 i V 1 ' 1 1 ' 1 1 ' 1 1 1_.___1_-_l____.'____ 0 I 1000 800 2000 1800 1600 1400 1200 III OUENCY lCM") Infrared Spectrum of ethyl 3—(3,4-dimethylpyrrol— Figure 10. 2—yl)propenoate, 221(CHC13). 92 7. 3.0 3.5 4.0 M'Ui’l‘r’i‘ 50 6.0 8.0 .. . . ' ‘ J - .. _. r.... . _._ _ _......_._._._.__1 “:0 w; :' H ; . 1 5 ' ‘ 100 '_i 'i i a i . : .. ... ... ao ‘ I , 60 40 TRANSMH TANCE(°o) lfi!-)'A:‘.e1‘(l.\ . 5.0 6.0 7.0 80 M'CRgNS' 19.0 11.0 12.0 .160 '00 ‘r I. 'l.‘ .: ' . ..'.:l. a. ..' l.. ., .7_ .1. _. 3 . . ' . ‘ . ; , E§E.i_;:ii§.i.i';.§i l.;i .v .lg'..‘00 1;. L. .91-?! - L; i I; ‘ ! : gil- :‘9:.:;i~:-i:jé§ 80 . i . - _ HI I J-.i_ ...l I ... ‘ ; I . 80 . i i E . l c l » I 7 . i 3' , 9 ' -.<~§ s,- 5- x 60 i 9 ' so A O TRANSMITTANCE {,3} 20 20 i I l I , i i i .. . I 0 _ : V ' ‘ . I ‘ 2000 1800 1600 I400 I200 1000 800 HtOUlNCV (CM'I Infrared spectrum of ethyl 3—(3,4—dimethylpyrrol— 2—y1)propanoate, EQQ’(CHC13) Figure 11. 93 "7f”: 100 I i i i < 80 .0- -- —‘-~— <~ ’ ' ‘- 7 ' ' I 4000 350:) 3£oo 2500 2000 1500 ralnutr. v bCM'D 5.0 I 6.0 7.0 8.0 M'CRONS no.0 11.0120 16.0 . . . 1 . . . A LJ.L4. ....1...,; ‘ .1. ' 100 I ' - »- I - - . g - - . - - I ’ - I z : ; 80% I \ I : .I . 7 ' “ :I = i : I 360 i ~r‘i z ; ; ' I < I E - -; , E, I I | - Z40 -1 _- H < z i m; ‘ I' 5.. . 20.. I I I I :If " 0 - II - 3c I I ; 5 e ' II I I I I 0 2000 1800 1600 I400 1200 1000 800 FREQUENCV [CM ') Figure 12. Infrared spectrum of ethyl 3—(5-carbethoxyethyl— 3,4-dimethylpyrrol—2-yl)propenoate, 101 (CHC13). 94 l 2.5 . 3.0 3.5 4.0 M'CRONS 5.0 6.0 8.0 I l | I . l l I | I l I i] I I J | I I I I ' I ' 100 - - "‘1“: E , I" -~;—-. I 100 80 TRANSMITTANCE _',.'_I TRANSMITTANCE I75) 60 40 I ’20 0 ' I I ' ' ’ ‘ ' ' 4030 3500 3000 2500 2000 1500 "IEOUENCV CM' 5.0 ' 6.0 7.0 80 M'CRONS Io.o 11.0120 16.0 -___ . I I .. ..I.I.4 |_ I II. __ 100 . i ._ In...” .; .. _;__-‘. r13. : I" ' . ‘ E . I . . 100 ' I I‘ I z = I . ' ‘ ' a I - ". _‘I . I I a .; II ,_. ;..: I 80 I _ ' 1 60 i 60 40 ' «‘0 20 I. 20 i I 0 ..... b I L __‘_____ ‘ _— I 0 2000 1800 1600 1400 1200 1000 800 iREOUtNCV (CM ' I Infrared spectrum of diethyl 3,4-dimethylpyrrole— Figure 13. 2,5—dipropanoate, 102 (CHC13). 95 .2.5 ‘ 3.0 3.5 4.0 M'CRONS 5.0 6.0 8.0 100 i , _ Ioo so I? E’ U 260 60 E L" 5 - : : - . 340 , 4o 2 .— 20 . I '1 ' . " 20 0 ' ' I 4000 3500 3000 2500 2000 - I500 moutucv (CM ‘) ' MICRON5 ”.0 12.0 16.0 TRANSMHTANCE(%) 1800 1600 1400 1200 1000 800 neouENCV (CM '1 of 3,4,3',4'—tetramethyl-dipyr— ' , frared s ectrum _ . Flgure 14 In p lotrimethine lodlde, iii ICHC13I- ryl—(2,2')—hexacyc 96 25 3.0 3.5 4.0 MICRONS 5.0 6.0 80 60 40 TRANSA’IITTANCE(91>1 20 O ‘ . . . . 4000 3500 3000 2500 2000 1500 II (mum v 1LM') 5.0 ' 6.0 7.0 8.0 M'CRQNS I0.0 11012.0 1 ,___ + I I I I I I I I l . I I I l 100 . . r . .. . A. __ :"T . I.“ __ . . z.“ . I 1 a I I :I , II. I I i . ' 'I ‘ ; _ I r. , I 3. 9 '7; " 0 O TRANSMHTANCEifi) 8.0 100 80 60 40 20 80 60 40 2O 40 -.--_ 2o ~~ I ———— ----___ —I—:~ I :I3 é1afs ; I II _-I I“€11”Jr"'T“‘I““T“I"‘“TI* *j— = s :1; - iI?‘III§I'€II'I II‘ II 1000 800 $000 1800 1600 1400 1200 "£005ch (CW) Infrared spectrum of 1,3—bis Figure 15. 2-yl)cyclohexane, 116 (CHCla). (3,4—dimethylpyrrol— 97 3.0 3.5 4.0 M'CRONS 5.0 6.0 80.0 ‘I IIIII IlillllllJ -I'II I- I I I I I- 80 ~— I -~i— ~ —-» _—--- ~ _ 4 i_.I_._ i_ --- _- TRANSMITTANCE(%) 40 --' - — — -« . I . I i _, _ :1 . : ' ..l. {.___ _._ .__—.__ .! I i I ‘9 20 -—~I»— —---;—~< _ i -E: I __ I i» 5 -_‘—— -__—.I _ Wmumcv IrM ') 5.0 ' 6.0 7.0 8.0 M'CRONS I00 I10 12.0 16.0 I I I I I ' I I I I ' I ‘ J ' I I . I I I I I I I '°° 7 " I I: . _ E, ..— l - _ «_-i .i [_l : I :;.| .. . : !.§i;.;"1}:; I : I i I I : ‘ . I 3 . l I 80 ‘ ‘ I": ' — T " " ‘é"‘”' E ' ‘ : 'I ' If: "’ 3' ' E ‘ , : g 2 M, I I < I . . : E, I i I I E Z40 - — w -— 5 i — —~ 3 ~ 40 § I E 1 E *- I I 5 ._ _ W _3 R I“- .41 ‘ I I E 20 _ '“ "H-_ d€~~w"_ 7"7 ; I -‘ i“ “T 0 2O 2 I z I I i I 7 I § ‘ 5 i ‘ E ! 0 2%00 1800 ’ 1600 1400 1200 1000 800 rlEouEch (CM'I Figure 16. Infrared spectrum of 5,5'—bis(carbethoxyethyl)— 3,4,3',4'—tetramethyl—dipyrryl—(2,2')-hexacyclo— trimethine iodide, i20 (CHCls). I 'l l ..fifi— , .L. r '4', ..i) I 71“I I‘LIT A. I I I I I ._._;I.A..I,...I .I .....I . . . . . . . . '0 1.0 CO 6.0 "M ‘3) to 1o 7;. IAILLI ! .0 9 Figure 17. NMR spectrum of ethyl 3,4-dimethylpyrrole—2—car— boxylate, fig (CDCla). fi— - v : 1 v v vfi v I 1 Yr r ! ,Ifi' v w I v 'v v u ! w 7 vv - g 1 1, T J» .1. 3L» Jo II.) I... ”9 I l I I J Hg I . . - I . . . I . I . I . . I . . . I . I I I o o u I o 1.0 rm W «o a.» u 1.0 0 Figure 18. NMR spectrum of ethyl 4,5-dimethylpyrrole—2-car— boxylate, §g,(CDCl3). WI 1 I . I . . I I . I I ._AAI.r..I....I.r. .I....I‘AI..I. IO 10 so so "“ng an 1° no I0 0 Figure 19. NMR spectrum of ethyl 3,4—dimethyl—5—iodopyrrole- 2—carboxylate, §§I(CDC13). TI 7 rgvr [fv'l' r I—fi—Vivvl I 'l' v—V—I—fi & A k l I Am ”9 111 I C II ni‘ 4:7“ ._‘L I l I J 1I II...I....Il...I...II.I.I .Ilo r+ Q “0‘ A . Am co up my," an [an :0 . Figure 20. NMR spectrum of ethyl 4,5-dimethyl—3—iodopyrrole— 2—carboxylate, §2 (CDC13). ' I I l I I I I g 77 I I I I I I I I l I I l I I I l l I V j ‘V—l—‘ I I I .L IN 0 \. ‘\ A l \ I ’4. sols/«at '—N I I I I I I I I I PJI II III III I III .II II. III ..I I. III I II III L14 no 10 so 5.0 pm‘!‘ no so 20 m o Figure 21. NMR spectrum of 2,5—bis(3—oxobutenyl)—3,4-dimethyl— pyrrole, Ql’((CF3)2C=O°1.5 H20). h%NMwwNvaMf ' .t T t _ -... v 7'1 . Hit. filly? . . ,‘ E John-‘1 .u f ’ I I I Figure 22. I II. II II II I n 70 50 6‘0 Pr'J 9‘ ‘0 3‘0 NMR Spectrum of 2 ,5—I).LS 113/din)“ but my -, (3- dimcthylwyrrol, 93,(C9913)- I I I I. I I .IIIIIIIIIIIII IIIIIII IIllI_1_I I I I I I I no 70 6.0 5.0 "MW :0 3,0 70 1.0 a Figure 23. NMR Spectrum of 2,5—bis(3-oxobutyl)—3,4—dimethyl— pyrrole, §§,(CDC13) W ‘ ‘ A 6,0 "‘14 I! .0 7.0 60 3—(3,4—dimethylpyrrol—2—yl)— propenoate, 22,(CDC13). Figure 24. NMR Spectrum of ethyl III I [II I I I I III 1 II] II rT—F-q——Tfi & $ k I ' k 1m 0 \ t I _ \ A; A 4». II 5 I I . __I_IlI IIIIIIIIIIIIIIIIIIIII I II, no ya so ”I“ "5.3) 40 Jo :o i u.) c- Figure 25. NMR spectrum of ethyl 3—(3,4-dimethylpyrrol—2—yl)— propanoate, 122’(CDC13). Insert: 100 MHz spec— trum of A2B2 pattern até 2.55. II .1 1. .37 L' J I III 1 I 1.. :I1 I k I i k i IL I" i ' \ \ It -— I I \ ¢H—;[ id l, I M‘ "'i’t-JMM'JIWIIIIL—I I n [I] II I I I I I I J_ giI I I I I I I I I I I I I I I I I I I I I I I I I I I I I no 10 no 3,0 nyfl‘fl to Jo 20 no 0 Figure 26. NMR spectrum of ethyl 3—(5—carbethoxyethyl—3,4— dimethylpyrrol-Z—yl)propenoate, 101 (CDC13). T_l I I’ I I I I I I I I I I I I I I I 1 I v I I v L W ’—I v T I *v VVVVVVVVVVVVVVVV r l v r vifi' ' v v v v v r Y '7 ‘r I r + i IL & m 2L IL (1)“: H. I I \ on \ I I‘ll It I 'l / \_ A A A AkA N“ w Jk—M 1 L L A l L A 4‘ L A I JJJJJJJ L l AAAAAA L J A A _A I L Li A I A L 4‘ I A A J L I ‘I A A ‘ I ‘ A A A I A A A ‘ I A A A J l A A J J; I J J A A T no no so 5.0 "M (:3 0.0 10 20 H) 0 NMR spectrum of diethyl 3,4—dimethylpyrrole—2,5— dipropanoate, 102 (CDC13). Insert: 100 MHz spec— trum of A232 pattern at t 2.67. Figure 27. l I I v v I I I I fir I I I I I l l I T T I I I ‘I Ifi 1 F I I I v I r v L V 7‘7' f Yfi—v V vvvvvvvvv T V v’ I Y vvvvv V V fl v v fl I .& II .L Igf IL II It. \ on I 0 I I OH ' I I I k M A v #I _J A A. A_ A A A I r I l A A AAAAAA l A L A _L A l A A A A J A A A J. A 1 g L A I A l g. A A J A A A A I A A L l A A 4 l A_. A A A l L A A A I A A A L 210 A A A ‘0 o 00 7.0 60 so nu I" to an Figure 28. oic I ..--t-al acid, 1,qu, (cncls) NMR spectrum of 3,4—dimethylpyrrole—2,S-diprOpan— IF‘ 104 . ..l 'J ..! .. ‘! .. .l . . I ... .I '1' .. 1 rsgrfi & k k ' k ' 1m ‘~\ (C33)2 “ \ (CH3)2 A l , I J I l ._. I l . A . l . . , . A . . . . . I . l . l . I so 70 co slo "5'41” .0 1o 20 ID 0 Figure 29. NMR spectrum of N,N,N',N',3,4—hexamethylpyrrole— 2,5—dipropanamide, 105 (CDCla). Insert: 100 Hz sweep width of spectrum at 8 2.77. I I ' I ' l r I ' l l ' l I '_' T u . ‘ ‘ I I Irv Figure 30. = 1 i i . ' - i . "5 I I 3 , . . ,1 t I ‘ *5 V v ‘ I i. ! :3 fi-m i‘ E‘ 1 Ha. I .5 ‘ ' u.i . i ! ‘ I . l l l l 1 I x i 11 i I 1 1 1 ' 1 A I; 99 to 10 an I10 4.0 n 1.9 NMR 8 ectrum of 3,4,3',4'-tetramethyl-dipyrryl- (2,2' —hexacyclotrimethine iodide, 115 (CDCl3). M l l | I l l I I l l . . . l I r l l A AL no to no \ 0'0 _pj-gfiifl £0 ,. :0 20 m o Figure 31. NMR spectrum of 1,3—bis(3,4—dimethylpyrrol—2-yl)- cyclohexane, {lg (CDCla). l l l to 1.0 Go up "ufll to so Figure 32. NMR spectrum of bis—2-(3,5-dimethyl—4—ethylpyrrole)— trimethine bromide, llZ,(CDC13>' l o m r L ! I 14 I Ii..rl....l.. IA-.+1L4 1° . . . . . . . . . A i so up "MI.” ‘0 no 20 w o Figure 33. NMR Spectrum of 1,3-bis(3,5—dimethyl—4—ethylpyrrol— 2—yl)propane, ¥l§.