Aromatic and Heteroaromatic Chemistry Volume 1

A Review of the Literature Abstracted between July 1971 and June 1972

By C. W. Bird, G. W. H. Cheeseman

The Royal Society of Chemistry

Copyright © 1973 The Chemical Society
All rights reserved.
ISBN: 978-0-85186-753-3

Contents

Chapter 1 Ring Systems of Topical Interest By C. W. Bird and G. W. H. Cheeseman,
Chapter 2 Intramolecular Cyclizations By A. Garry and S. F. Dyke,
Chapter 3 Condensation Reactions By R. C. Brown and S. F. Dyke,
Chapter 4 Cycloaddition Reactions By G. V. Boyd,
Chapter 5 Ring Interconversions By A. J. Boulton,
Chapter 6 Electrophilic Substitution on Carbon By R. Taylor,
Chapter 7 Electrophilic Substitution on Hetero-atoms By C. W. Bird and G. W. H. Cheeseman,
Chapter 8 Nucleophilic Substitution By G. B. Bar/in,
Chapter 9 Aromatic Substitution by Free Radicals, Carbenes, and N itrenes By S. R. Chai/and,
Chapter 10 Addition Reactions By G. V. Boyd,
Chapter 11 Ring-cleavage Reactions By T. L. Gilchrist,
Chapter 12 Reactions of Substituents By J. W. Barton,
Chapter 13 Porphyrins and Related Compounds By K. M. Smith,
Chapter 14 Naturally Occurring Oxygen-ring Compounds By D. E. Games,
Chapter 15 Other Naturally Occurring Aromatic Compounds By C. W. Bird and G. W. H. Cheeseman,
Author Index, 426,

CHAPTER 1

Ring Systems of Topical Interest

BY C. W. BIRD AND G. W. H. CHEESEMAN

1 Introduction

Over the past few decades theoretical views on aromaticity have led many chemists to undertake the synthesis of exotic molecules whose properties might further refine our understanding of this concept. A timely introduction to this fascinating field has recently appeared and has inevitably influenced the organization of this chapter. The recent publication of the invited lectures given at the ‘International Symposium on the Chemistry of Nonbenzenoid Aromatic Compounds’ held in Japan in 1970 provides a valuable insight into current developments. Topics covered are best illustrated by quoting the lecture titles: ‘Quantitative studies on aromaticity and antiaromaticity’; ‘ESR studies of some non-benzenoid radical ions’; ‘Structure and reactivity of polycyclic cross-conjugated π-electron systems’; ‘The theoretical design of novel stabilised systems’; ‘Aromaticity in macrocyclic polypyrrolic ring systems’; ‘Bond distortions in nonaltemant hydrocarbons’; ‘Recent advances in the chemistry of troponoids and related compounds in Japan’; ‘Cyclic cross-conjugated π-systems: (J.W-cycloaddition reactions’; ‘Recent progress in the annulene field’; ‘Aromatic and nonaromatic 14π-electron systems’; ‘Conjugated cyclic chlorocarbons: trichlorocyclopropenium ion, heptachlorotropenium ion, and octachloro-fulvalene’. A critique of the concept of aromaticity and the methods used to define it has also appeared.

2 Valence Isomers

Despite its accepted role in many photochemical reactions of benzene, the generation of appreciable quantities of benzvalene for chemical study has proved very difficult. The photochemical conversion of benzene into benzvalene (1) gives at best 1% of the latter. An attractive route to (1), based on the conversion of cyclononatetraenyl anion into isobullvalene, utilizes the reaction of lithium cyclopentadienide with dichloromethane and methyl-lithium. The compound is best handled in solution, as neat samples readily detonate. An analogous procedure applied to indene provides naphthvalene (2), which is apparently much more stable. On heating (175°C) it is converted into benzofulvene. Benzvalene has been implicated as an important intermediate in the photo-oxidation of benzene in aqueous solution to cyclopenta-1,3-diene-1-carboxaldehyde. Oxygen is not required for formation of the photoaldehyde. Two molecules of benzvalene are consumed per molecule of photoaldehyde generated. In the absence of oxygen the other benzvalene molecule is converted into cyclohexa-1,4-diene.

One of the pathways of photoracemization of optically active 6,6′-diethyl-2,2′ -dimethylbiphenyl involves reversible benzvalene formation. The decreased size of the benzvalene ring compared to the original aromatic one results in a lowered barrier for interconversion of the enantiomers.

A full account of previously reported preparations of Dewar-benzenes has appeared. This covers not only the photochemical conversion of 1,2,4-tri-t-butylbenzene into 1,2,5-tri-t-butylbicyclo[2,2,0]hexa-2,5-diene but also the generation of the parent bicyclo[2,2,0]hexa-2,5-diene (3) (Scheme 1). An extensive study of the non-aromatization reactions of (3) has also been described. 18 A new general route to these compounds is provided by the silver-perchlorate-mediated rearrangement of bicyclopropenyls (4), which proceeds via the Dewar-benzene (5) to the aromatic hydrocarbon; the first step is faster than the second.

3 Helicenes

The chemistry of this class of compounds has started to receive much more attention with the development of a facile photochemical synthesis from cis-1,2-diarylethylenes. For example, cis-1,2-di-(2-naphthyl)ethylene is converted into 4a,4b-dihydro-3,4,5,6-dibenzophenanthrene (6) on u.v. irradiation. Dehydrogenation by atomic iodine, but not molecular iodine or oxygen, converts (6) into the dibenzophenanthrene (pentahelicene) (7). The most interesting development in this area is the finding that use of circularly polarized u.v. light results in the generation of helicenes with a small preponderance of one of the two enantiomers. Thus photocyclization of (8) or (9) with right circularly polarized light provides hexahelicene (10) containing an excess of the (–)-enantiomer. The optical yield is of the order of 0.20%. Of particular interest in this respect is the demonstration by X-ray crystallography that (–)- hexahelicene has left-handed helicity. This partial asymmetric synthesis apparently results from selective reaction of enantiomeric configurations of the cis-diarylolefins. The alternative proposition that the process entails partial asymmetric destruction of hexahelicene is excluded by the demonstration that irradiation of ([+ or -])-hexahelicene with right circularly polarized light preferentially destroys the (-)-isomer. Similar partial asymmetric syntheses of hepta-, octa-, and nona-helicenes have been reported. The same basic approach has also been applied to the synthesis of heterohelicenes such as (11), (12), (13), (14), and (15). The compounds (11; Y = S), (13), and (14) give a mixture of (+) and(-) crystals and can be resolved by hand-picking. Resolution of (13) was also achieved by fractional crystallization from (–)-α-pinene. Solutions of optically active (14) racemized fairly rapidly at room temperature (t1/2 = 13 min at 25°C). The much lower optical stability of (14), relative to hexahelicene, is due to the reduced overcrowding in the former. Whereas the angle between the two formal carbon-carbon double bonds which take part in the annelation to form a helicene is 60° for a benzene ring (16), the corresponding figure for thiophen (17) is 45°. Hence a full turn of the helix (360°) requires 6 benzenoid rings or 8 thiophen rings. An unexpected feature of the hexahelicenes is the facile ring-closure, e.g. (14) to (18), which they undergo on treatment with A1Cl3 in benzene at 20°C.

Analysis of the n.m.r. and u.v. spectra of 2-substituted hexahelicenes indicates that substituents as large as t-butyl or p-tolyl have little effect on the helical conformation. However, introduction of large substituents such as t-butyl at position 1 [cf. (10)] necessitates bending of the alkyl group or distortion of the ring in order to relieve steric crowding. 2,2′-Bishexahelicyl (19) has been synthe-sized and separated chromatographically into meso and racemic forms. The 1H n.m.r. spectra suggest that the central biphenylic portion of the meso-compound is rather planar, whereas in the racemic compound the molecule is twisted around the central bond.

4 Circulenes

Reaction of the helicene (18) with maleic anhydride, followed by decarboxylation with copper powder-quinoline, provides the compound (20), which has been termed a [7]heterocirculene. Previously known compounds of the newly termed ‘circulene’ family are coronene ([6]circulene) (21) and corannulene ([5]circulene) (22).

5 Sterically Overcrowded Molecules

The reaction of 4a-azonia-anthracene salts [e.g. (23)] with keten acetals has made available a number of overcrowded molecules [e.g. (24), Scheme 2]. The u.v. and 1H n.m.r. spectra of these compounds show abnormalities which are interpreted as manifestations of ring strain. For example, the u.v. spectrum of (24) shows marked bathochromic shifts compared with the compound lacking the peri-t-butyl group. Perhaps the most convincing sign of the marked steric repulsions between the 2-pyridyl and t-butyl groups is provided by the adoption of the keto tautomeric form (25) by the product of deacetylation of (24). Analogous synthetic reactions have been used to generate, inter alia, (26) and (27). In these molecules also the spectral properties pay testimony to the molecular distortions occasioned by steric overcrowding. In the case of the mono N-methyl quaternary salt (28) it is clear from n.m.r. studies that the pentaphene is undergoing ring inversion accompanied by a synchronous rotation of both pyridine moieties. The free-energy barrier for this process is estimated at less than 17 kcal mol-1 which, since this is the energy difference between the planar transition state and the ground state, emphasizes the high energy of the latter.

6 Bridged Aromatic Ring Compounds

[2,2]Paracyclophanes. — A review of recent developments in the chemistry of this class of compounds has appeared. An ever-widening range of p-cyclophanes with new structural features are being synthesized (cf. Chapter 4, Section 2). As anticipated, all compounds show the presence of strong interactions between the aromatic rings. Effects are of course more pronounced in the triple-layered compounds than in the double-layered ones, and the aromatic protons of the former are observed at higher fields than are the corresponding ones in the latter compounds. Similarly, the u.v. spectra of the triple-layered compounds exhibit a marked bathochromic effect relative to those of the double-layered ones. The π-basicity of these cyclophanes can be evaluated from the absorption maxima of tetracyanoethylene-cyclophane complexes. Comparison of the π-basicities of layered heterophanes and their benzenoid counterparts suggests that the electronic interaction between heteroaromaticringand benzene ring is less pronounced than that between benzene rings.

A particularly interesting facet of the 1H n.m.r. study of compounds (29), (30), and (31) is the observation that the furan ring in (29) can undergo inversion at room temperature whereas rotation of the thiophen ring is not observed up to 150°C. This is probably a reflection of the differing sizes of oxygen and sulphur atoms. The inversion of the furan ring in (29) proceeds with slightly greater facility than in the case of (32).

Thermally mediated (ca. 200°C) ring inversions of [2,2]paracyclophane have previously been shown to proceed via homolytic fission of the benzyl-benzyl bond to give a biradical. Similar intermediates are formed in the photolytic racemization of (33) and (34). Although racemization is the faster process, open-chain products of the biradical are slowly accumulated. The intermediacy of biradical species receives further support from the thermal and photochemical transformations of 1-vinyl[2,2]paracyclophanes [e.g. (35)]. This compound is converted via (36) into (37). In the presence of dimethyl maleate or fumarate, biradical (36) is intercepted, yielding (38) and (39). The rate of rearrangement of (35) into (37) was unchanged in going from benzene to methanol as solvent.

Cleavage of the methylene bridge has also been observed in a study of the anion radicals of [2,2]paracyclophanes. These anion radicals are only stable at temperatures below -70°C, in direct contrast to their simple aromatic counterparts. These species readily accept another electron by disproportionation or direct reduction. This unstable 2-electron reduced species then undergoes bond scission with formation of the aryl methide anion (ArCH2-).

Despite the apparently grossly sterically unfavourable geometry, experimental evidence suggests that solvolysis of 1-tosyloxy[2,2]paracyclophane (40) proceeds via a phenonium ion. Acetolysis, methanolysis, and trifluoroacetolysis of the optically active tosylate all proceed with complete retention of configuration. The acetolysis rates are about 100 times faster than those of aliphatic secondary tosylates.

Nitroxide derivatives of [2,2]paracyclophane have been prepared for e.s.r. studies. It was found that oxidation of two of the monohydroxy-t-butylhydroxylamines (41) and (43), encountered in this work, produced the t-butylamino[2,2]paracyclophanequinones (42) and (44) by a route involving transannular oxygen migration (see Scheme 3).

[2,2]Metaparacyclophanes. — A review of the stereochemistry and chemical reactions of this class of compounds has appeared. A detailed report of the acid-catalysed isomerization of [2,2]paracyclophane into [2,2]metaparacyclophane (45) is now available. Apart from polymers, the only other characterized product is the hexahydropyrene (46). The main driving force is the decrease in strain energy of some 8 kcal mol-1 in this transformation, which is largely a result of decentering the rings with a resultant decrease in π-π repulsions. However, the p-substituted ring of (45) is more deformed than those of its precursor and the meta-substituted ring is bent into an inclined chair.

The extension of the isomerization reaction to 4-substituted paracyclophanes has been examined. No success was obtained with 4-acetyl, 4-methoxycarbonyl, or 4-cyano-derivatives, but the reaction proceeds satisfactorily with the 4-methyl and 4-bromo-compounds. Subsequently the rearrangement of optically pure (+)-(S)-4-methyl[2,2]paracyclophane into optically pure (+)-(S)-12-methyl[2,2]-metaparacyclophane has been reported.

The ring rotation of [2,2]metaparacyclophane and its derivatives has been studied. Crystallization provides only the 12-isomer (47). This isomer is also preferred at -50°C in CDC13, but at 37°C the 1H n.m.r. spectrum shows the presence of a mixture of 12-(47) and 15-isomers (48). Equilibrium constants for a series of monosubstituted compounds are reported. Observation of the aliphatic protons indicates that the meta ring rotates. The optical stability, up to 200°C, of the optically active 12-methoxycarbonyl compound indicates that the para-substituted ring does not rotate. Rotation of both rings would result in racemization.

Bromination of (45) gives 63 % of the 13-and 15-bromo-derivatives, which interconvert at room temperature, and 37% of 4-bromo-compound. Friedel-Crafts acetylation of (45) provides a mixture of 13(15)-and 4-monoacetyl derivatives, along with the tetracyclic ketone (49). In HSO3F-SO2Cl2-CH2Cl2 solution at -80 to -98°C metaparacyclophane is protonated at position 11(14). In deuteriotriftuoroacetic acid all positions of (45) undergo isotopic exchange at about the same rate except for the very hindered 8-position. Cleavage of (45) with potassium provides 3′,4-dimethylbibenzyl. Metaparacyclophane is photo-chemically isomerized into [2,2]metacyclophane. (-)-(R)-12-Methyl [2,2]-metaparacyclophane undergoes photochemical racemization at about the same rate as it rearranges into a mixture of 4-, 5-, and 8- methyl[2,2]metacyclophanes. However, the racemization appears to involve homolytic cleavage of the ethano-bridge to give a biradical species whereas the rearrangements proceed via prismane or benzvalene intermediates.

Metacyclophanes. — Another member (50) of the bridged syn-metacyclophane family has been synthesized from phenothiazine (Scheme 4). In accord with other members of this family, (50) undergoes thermal extrusion of the methyl-amino-bridge to give the phenanthrothiophen (51). A new synthetic approach to [2,2]metacyclophanes is indicated by the preparation (Scheme 5) of (52). Although [2,2]metacyclophane has a fairly rigid conformation (ΔG≠ > 27 kcal mol-1), increasing the ring size by insertion of sulphur atoms in the methylene bridges lowers the energy barrier to conformational change. Thus ΔG≠ is 13 kcal mol-1 for (53) and less than 9 kcal mol-1 for (54). In the case of (53) the value of ΔG≠ increases in the sequence sulphide

Treatment of [2,2]metacyclophanes with iodine in benzene at 60°C results in the formation of 1,2,3,3a,4,5-hexahydropyrenes [e.g. (46)]. The results of experiments using deuteriated precursors indicate the occurrence of an intermolecular hydrogen-transfer process.

Polymethylene-bridged Systems. — Several compounds of this class have been obtained by application of standard methods of ring formation to appropriately substituted cycloalkanes. Thus 3-acetylcyclononanone yields the thiophen (55) with phosphorus pentasulphide and N-arylpyrroles (56) with arylamines. The [7](2,6)pyridinophane (57) and the pyrylophanium perchlorate (58) have been prepared from cyclododecane-1,5-diones. The synthesis of the [9]2,4-pyridinophane (61) and of the [9]metacyclophane (62) from cyclododec-2-enone followed the routes shown in Scheme 6. A novel synthesis of the [7]meta-cyclophanes (59) and (60) from cyclodecane-1,4-dione has been mentioned elsewhere (Chapter 5, Section 3).

(Continues…)Excerpted from Aromatic and Heteroaromatic Chemistry Volume 1 by C. W. Bird, G. W. H. Cheeseman. Copyright © 1973 The Chemical Society. Excerpted by permission of The Royal Society of Chemistry.
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