Aromatic and Heteroaromatic Chemistry Volume 2

A Review of the Literature Abstracted between July 1972 and June 1973

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

The Royal Society of Chemistry

Copyright © 1974 The Chemical Society
All rights reserved.
ISBN: 978-0-85186-763-2

Contents

Chapter 1 Ring Systems of Topical Interest By C. W. Bird and G. W. H. Cheeseman, 1,
Chapter 2 lntramolecular Cyclizations By A. W. Somerville, 66,
Chapter 3 Condensation Reactions By P.A. Lowe, 106,
Chapter 4 Cycloaddition Reactions By G. V. Boyd, 135,
Chapter 5 Ring lnterconversions By A. J. Boulton, 179,
Chapter 6 Electrophilic Substitution on Carbon By R. Taylor, 217,
Chapter 7 Electrophilic Substitution on Hetero-atoms By E. F. V. Scriven, 258,
Chapter 8 Nucleophilic Substitution By G. B. Barlin, 271,
Chapter 9 Aromatic Substitution by Free Radicals, Carbenes, and N itrenes By S. R. Challand, 297,
Chapter 10 Addition Reactions By G. V. Boyd, 316,
Chapter 11 Ring-cleavage Reactions By T. L. Gilchrist, 370,
Chapter 12 Reactions of Substituents By J. W. Barton, 382,
Chapter 13 Porphyrins and Related Compounds By K. M. Smith, 423,
Chapter 14 Naturally Occurring Oxygen-ring Compounds By D. E. Games, 447,
Chapter 15 Other Naturally Occurring Compounds By R. H. Thomson, 472,
Author Index, 495,

CHAPTER 1

Ring Systems of Topical Interest

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

1 Introduction

As organic chemists attach a diversity of meanings to the term ‘aromatic’, a current article suggests that the use of this term be discontinued and be replaced by the words regenerative or meneidic. A recently published book entitled ‘The Aromatic Sextet’ is concerned mainly with polycyclic hydrocarbons and also provides a review of the author’s extensive contributions to this subject.

The use of the readily prepared 4-methyl-2,6,7-trioxabicyclo[2,2,2]octane (1) as a ring-current probe has been suggested. The 1H n.m.r. absorptions of (1) undergo pronounced upfield and downfield shifts in the proximity ofthe shielding cone and deshielding torus, respectively, ofcarbocyclic and heterocyclic molecules possessing a ring current. Thus the methyl protons of the probe molecule experience substantial upfield shifts in thiophen, tellurophen, pyrrole, and benzene, whereas a negligible shift occurs in cyclo-octatetraene. The comparable chemical shifts of the methyl group of (1) in furan and cyclopentadiene suggest that furan is only weakly aromatic. Orientational effects in highly polar solvents such as nitrobenzene are discussed.

The estimation of aromatic resonance energies from tautomeric equilibria has been further studied. The resonance energy of the benzene ring of phenol was determined as 31 [+ or -] 6 kcal mol-1 from the enthalpy differences for the cyclohexanone-cyclohexanol and the phenol-cyclohexa-2,4-dienone equilibria. Aromatic resonance energies have also been estimated for uracil, pyrrole (27 [+ or -] 4 kcal mol-1), carbazole (79 [+ or -] 9 kcal mol-1), and isoquinoline (48 [+ or -] 9 kcal mol-1).

2 Valence Isomers

A useful introductory survey of valence-bond isomers of aromatic systems has appeared.

The first synthesis of prismane (2) has been reported, cf Scheme 1. The temperature used for the photolysis of the azo-compound is important since whereas a yield of 8%of prismane is obtained at 30°C, none is obtained at -65°C. The other products of the photolysis are benzene and 1,2-diazacyclo-octatetraene. Prismane is stable at room temperature and undergoes conversion into benzene with a half-life of 11 h at 90°C.

The introduction of a chlorine or fluorine substituent at C-1 of bicyclo[2,2,0]-hexa-2,5-diene accelerates the rearrangement to halogenobenzenes by factors of ca. 90 and 370 respectively, whereas the 1,4-dichloro-compound rearranges some 620 times slower than the parent hydrocarbon. It is suggested that the effect is due to stabilization of the antiaromatic transition state, resulting from disrotatory opening, by the unsymmetrical substitution.

Hemi-Dewar naphthalene (3) has been synthesized by addition of benzene to 3,4-dichlorocyclobutene and subsequent dechlorination. The first instances of photoisomerization of naphthalenes to hemi-Dewar naphthalenes are exemplified by conversion of 1,3,8-tri-and 1,3,6,8-tetra-t-butylnaphthalenes mto (4) and (5), respectively.

3 Polybenzenenoid Compounds

K-Region oxides are probably responsible for the carcinogenic activity of the parent hydrocarbons. A new general synthesis of these compounds has been developed (Scheme 2) and applied to the synthesis of such compounds as (6) and (7).

A new and improved approach to the non-K-region oxides has also been described utilizing halohydrin trichloro-or triftuoro-acetates, cf Scheme 3. Excellent yields of naphthalene 1,2-epoxide and phenanthrene 3,4-epoxide have been obtained by this route.

Tetrabenzoperopyrene (8) is of particular interest because no Kekule structure can be written for it although it is clearly alternant. An attempt to prepare (8) by reducing condensation of naphthanthrone (9) produced instead the hydrocarbon (10), named circobiphenyl.

4 Helicenes

The absolute asymmetric synthesis of helicenes from diarylethylenes by irradiation with circularly polarized light has been further explored and it is concluded that it is due to selective excitation of the enantiomers of the parent olefins. An optically active dihydropentahelicene intermediate has been detected in the photocyclization of cis-di-β-naphthylethylene with circularly polarized light. Of course the optical yield in these cyclizations is small and pure optical isomers can still only be obtained by resolution. An original approach to this problem is indicated by the resolution of 7-methylhexahelicene. Treatment with N-bromosuccinimide gave the bromomethylhexahelicene which was further treated with trimethylphosphine, giving the quaternary phosphonium bromide. The latter was converted into the (-)-D-hydrogen dibenzoyltartrate and fractionally crystallized. The resulting pure diastereoisomeric salt was reconverted into the quaternary phosphonium bromide, which on stirring with aqueous sodium hydroxide generated (-)-7-methylhexahelicene. (+)-Pentahelicene has been shown to have the right-handed helical (P)-configuration by synthesis from (-)-(S)-2,2′-bis(bromomethyl)-1,1′-binaphthyl. The absolute configuration of hexahelicene has also been established by a chemical method. The diaryl-ethylene (12) was obtained by a Wittig reaction with the (-)-(R)-aldehyde (11). For steric reasons photochemical ring closure of (12) can only provide (13) with a left-handed helix. Comparison of the o.r.d. curves of the resulting (-)-isomer of (13) with that of (-)-hexahelicene showed that both compounds had the same chirality. [6]-, [7]-, [8]-, and [9]-helicenes undergo racemization when heated slightly above their melting points. Initial kinetic data indicate that the process does not occur by bond breaking.

The double helicene (15) has been synthesized by photochemical cyclization of (14), which was prepared by a Wittig reaction from naphthalene-2,6-dialdehyde and 3-(2-bromophenanthryl)methylenetriphenylphosphorane. Both meso-and dl-isomers of (15) resulted and configurational assignments were made by n.m.r.

5 Sterically Overcrowded Molecules

The diastereomeric biphenyl derivatives (16) and (17) have been prepared as the first examples of compounds with an axis of pseudo-asymmetry. Several instances have been reported in which optically active 2,2′-and 4,4′-dibromo-3,3′-bithienyls, on reaction with alkyl-lithium at -70°C followed by carbonation, yield racemic dicarboxylic acids which are known to have optically stable enantiomers. The classical mechanism of biaryl racemization via a cis- or trans-coplanar conformation is unlikely in this case because of the size of the substituents and the low temperature. The racemization probably results from the formation of an achiral intermediate in which the aromatic rings are coplanar (cis) and each of the two lithiums is bonded to both rings.

In 1,8-di-t-butylnaphthalenes steric interactions cause considerable twisting so that the t-butyl groups are on opposite sides of the mean plane of the naphthalene ring. The energy barrier to the flipping of these groups to give a mirror-image conformation is in excess of 24 kcal mol-1. In contrast the barrier to rotation about the t-butyl-naphthalene bonds is relatively low, ca. 6.5 kcal mol-1.

Oxidation of the overlapped pyridyl compounds (18) and (19) has provided the more highly overcrowded isoxazolium compounds (20) and (21). Whereas reaction of (20) with nucleophiles gives products resulting from addition at C-8a (BH4-,OH-, OMe-) or substitution at C-7 (CN-) through an apparent 1,6 addition-elimination, the reaction of (21) with nucleophiles gives products resulting from the more standard reduction (BH4-) or substitution (CN-) of the pyridinium ring. The differing reactivities of (20) and (21) may be caused by the intramolecular charge-transfer properties of the former compound lowering the electrophilic character of the pyridinium ring.

6 Bridged Aromatic Ring Compounds

The various methods so far used for the synthesis of [2,2]phanes have been comprehensively reviewed.

[2,2]Paracyclophanes. — A simple synthesis of this class of compound has been effected by the addition of dimethyl acetylenedicarboxylate to hexa-1,2,4,5-tetraene (cf. Chapter 4, p. 145). The pyrolysis of appropriate (p-methylaryl-methyl)trimethylammonium hydroxides has been used to prepare a number of paracyclophanes (cf. Chapter 4, pp. 145-148).

An X-ray structural determination on the tetramethyl four-layered cyclophane (22) shows that the outer benzene rings are very similar to the boat-shaped rings of [2,2]paracyclophane. The inner benzene rings are distorted into a twist shape.

Of particular interest is the extent of transannular π-π interactions in these molecules. The use of u.v.-spectroscopic studies of tetracyanoethylene complexes is shown to be ineffectual for this purpose. 33 The ratios of the two dissociation constants for the bis(tricarbonylchromium)complexes of [2,2]paracyclophane, [2,2]metacyclophane, and 2,2′-spirobi-indane have been determined as > 104, 9.0 [+ or -] 1.9, and 8.0 [+ or -] 1.5, respectively. These indicate the expected large interaction in the [2,2]paracyclophane and the absence of any appreciable interaction in [2,2]metacyclophane.

Electrophilic additions of bromine and hydrogen bromide to 1,2-dehydro[2,2]-paracyclophane (23) follow a cis stereochemical course. Acetolysis of the addition products also proceeds with retention of configuration. These observations provide additional evidence for the intervention of highly strained phenonium ion intermediates in side-chain reactions of this paracyclophane. The formolysis of the threo-tosylate (24) proceeds 68 times faster than that of the erythro-isomer (26). In the former case the exo-bridged ion (25) is an intermediate, whereas the endo-bridged ion (27) is involved in the later instance.

[2,2]Metaparacyclophanes. — Various aspects of the stereochemistry of [2,2]meta-paracyclophanes have been reviewed. The inverse conformational kinetic isotope effect for ring flipping in 8-deuterio[2,2]metaparacyclophane (28) has been determined. The unusually large value, kD/kH = 1.20, reflects the rigidity of (28), which causes a larger compression of the carbon-8-hydrogen bond than has been encountered in previously studied examples.

[2,2]Metacyclophanes. —l-Oxo[2,2]metacyclophane (29) and the axial and equatorial isomers of 1-hydroxy[2,2]metacyclophane (30) have been synthesized and resolved. The kinetic parameters for the ring inversion of the axial hydroxy-compound are ΔH≠ 31.7 [+ or -] 1.7kcal mol-1, ΔG≠150 32.9 kcal mol-1, and ΔS≠ -2.75 [+ or -] 4.0 e.u. The corresponding values for the equatorial alcohol are ΔH≠ 29.6 [+ or -] 1.7 kcal mol-1, ΔG≠150 33.2kcal mol-1, and ΔS≠ -8.5 [+ or -] 4.0 e.u. The equatorial to axial equilibrium constant is 1.49 at 151.5°C. Although inspection of molecular models indicates that the inversion process in the ketone should occur with comparable facility the kinetic parameters, ΔH≠ 10.75 [+ or -] 0.19 kcal mol-1, ΔG≠150 25.05 kcal mol-1, ΔS≠ -48.4 [+ or -] 0.6 e.u., indicate that the transition state is extraordinarily rigid.

The previously observed iodine-catalysed conversion of [2,2]metacyclophane (31) into the hexahydropyrene (32) has been extended to various alkyl-substituted derivatives. Appropriate experiments utilizing deuterium-labelled compounds show that the reaction is accompanied by intermolecular hydrogen transfer.

Despite indications that there is little transannular interaction in [2,2]meta-cyclophane, the electronic absorption spectra of the newly synthesized layered metacyclophanes (33) and (34) show features best explained on this basis.

Other Bridged-ring Systems. — The smallest paracyclophane previously known had an octamethylene bridge. Two syntheses of heptamethylene-bridged derivatives have now been effected. One utilizes the contraction of a derivative of the corresponding octamethylene compound, and the other produces [7]paracyclophane (36) by flash pyrolysis of the lithium salt of (35) in 20% yield. The electronic spectra indicate that the aromatic ring is substantially deformed.

The 1,12-dioxa[12]paracyclophane derivatives (37) and (38) have been synthe-sized as the first examples of diastereomers with a plane of pseudoasymrnetry.

Interest is developing in the synthesis of cyclophanes containing unsaturated groupings in the bridge. Several paracyclophadiynes (39; m = 2, n = 4; m = n = 3; m = 3, n = 4; m = n = 4; m = n = 5) have been generated by intramolecular oxidative coupling of the corresponding bisethynyl compounds. The abnormal electronic spectra observed for (39) with m = n = 3 and m = 3, n = 4 are attributed to transannular π-electronic interaction between the benzene nucleus and the diacetylenic unit. Quoted X-ray data for (39; m = n = 3) show inter alia that the benzene ring is less distorted than in [3,3]paracyclophane and that the atomic group C-C[equivalent to]C-C[equivalent to]C-C is forced to bend by 6-11° from its normal linear arrangement. The shortest distance between the two n-electronic systems is ca. 3.07 Å. The diacetylenic unit lies immediately over the 1-and 4-positions of the benzene ring rather than adopting a skew arrangement as suggested by models. Appreciable transannular interaction has also been observed between the benzene nucleus and hexapentaene group in (40), whose synthesis is indicated in Scheme 4.

The formation of the novel allenic furanophane (41) (Scheme 5) has been reported.

Some unexpected reactions involving cyclophanes have been encountered. Treatment of 12-bromo[6]metacyclophane (42) with butyl-lithium and subsequent quenching in deuterium oxide gave the expected (43) accompanied by the tetrahydroacenaphthene (44). No analogous cyclization reaction was observed with the heptamethylene homologue. Compound (44) also resulted from u.v. (42) irradiation of an ethanolic solution of (42). The naphthalenophane (45) failed to undergo base-catalysed elimination to (46), preferring to undergo a Stevens rearrangement leading to (47).

The conformational behaviour of cyclophanes continues to attract much attention. The energies of activation for the rotation of the benzene ring in cis-(48) and trans-[12]paracyclophanes (49) have been determined. Activation energy differences between individual cis-trans pairs are ca. 0.5 kcal mol-1. The activation energies for the dibromo-and diacetoxy-compounds are ca. 13 kcal mol-1 and those for the dihydroxy-compounds ca. 18 kcal mol-1. The higher values in the latter case are ascribed to intermolecular hydrogen-bonding. The indicated free energies of activation for the paracyclophane derivatives (50) and (51) have been measured by n.m.r. lineshape methods. Noteworthy is the rapid increase in the free-energy barrier to rotation of the benzene rings as the length of the polymethylene bridge is decreased in both (50) and (51). The thiomethyl group in (51) increases ΔG≠ for rotation of the adjacent benzene by ca. 2 kcal mol-1. Bridge inversion processes (52) [??] (53) with X = S or SO2 are observed at low temperatures and entail lower free energies of activation than are required for rotation.

The temperature dependences of the 1H n.m.r. spectra of (54) and (55) are interpreted by assuming that each of these [6]metacyclophanes can exist as two conformers which equilibrate at room temperature by pseudorotation. The estimated energy barriers are 11.l kcal mol-1 for (54) and 12.4 kcal mol-1 for (55).

(Continues…)Excerpted from Aromatic and Heteroaromatic Chemistry Volume 2 by C. W. Bird, G. W. H. Cheeseman. Copyright © 1974 The Chemical Society. Excerpted by permission of The Royal Society of Chemistry.
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