March's Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, 7th Edition (2013)

Chapter 2. Delocalized Chemical Bonding

2.K. Aromatic Systems with Electron Numbers Other than Six

The special stability of benzene is well recognized, and this stability is also associated with rings that are similar, but of different sizes, (e.g., cyclobutadiene (77), cyclooctatetraene (78), cyclodecapentaene (79)²¹²,

and so on. The general name annulene is given to these compounds,²¹³ benzene being [6]annulene, and 77–79 being called, respectively, [4], [8], and [10]annulene.²¹⁴ By a naïve consideration of resonance forms, these annulenes and higher ones should be as aromatic as benzene. Yet they proved remarkably elusive. The ubiquitous benzene ring is found in thousands of natural products, in coal and petroleum, and is formed by strong treatment of many noncyclic compounds. None of the other annulene ring systems has ever been found in nature and, except for cyclooctatetraene, their synthesis is not simple. Obviously, there is something special about the number six in a cyclic system of electrons.

Hückel's rule, based on MO calculations,²¹⁵ predicts that electron rings will constitute an aromatic system only if the number of electrons in the ring is of the form 4n + 2, where n is zero or any position integer. Systems that contain 4n electrons are predicted to be nonaromatic. The rule predicts that rings of 2, 6, 10, 14, and so on, electrons will be aromatic, while rings of 4, 8, 12, and so on, will not be. This is actually a consequence of Hund's rule. The first pair of electrons in an annulene goes into the π orbital of lowest energy. After that the bonding orbitals are degenerate and occur in pairs of equal energy. When there is a total of four electrons, Hund's rule predicts that two will be in the lowest orbital, but the other two will be unpaired, so that the system will exist as a diradical rather than as two pairs. The degeneracy can be removed if the molecule is distorted from maximum molecular symmetry to a structure of lesser symmetry. For example, if 77 assumes a rectangular rather than a square shape, one of the previously degenerate orbitals has a lower energy than the other and will be occupied by two electrons. In this case, of course, the double bonds are essentially separate and the molecule is still not aromatic. Distortions of symmetry can also occur when one or more carbons are replaced by heteroatoms or in other ways.²¹⁶ The enthalpy of formation of cyclobutadiene was reported by Kass and co-workers.²¹⁷ There is a brief discussion of the importance of cyclobutadiene with respect to antiaromaticity.²¹⁸ A word of caution is in order for MO calculations in these systems. It is known that ab initio computations on benzene at electron-correlated MP2, MP3, CISD, and CCSD levels using a number of popular basis sets²¹⁹ give anomalous, nonplanar equilibrium structures. ²²⁰ The origin of these anomalies has been addressed.²²⁰

In the following sections, systems with various numbers of electrons are discussed. Any probe of aromaticity must include (1) the presence of a diamagnetic ring current; (2) equal or approximately equal bond distances, except when the symmetry of the system is disturbed by a heteroatom or in some other way; (3) planarity; (4) chemical stability; (5) the ability to undergo aromatic substitution.

2.K.i Systems of Two Electrons²²¹

Obviously, there can be no ring of two carbon atoms (a double bond may be regarded as a degenerate case). However, by analogy to the tropylium ion, a three-membered ring with a double bond and a positive charge on the third atom (the cyclopropenyl cation) is a 4n + 2 system and expected to show aromaticity. Unsubstituted 80 has been prepared,²²² as well as several derivatives, (e.g., the trichloro, diphenyl, and dipropyl derivatives), and they are stable despite bond angles of only 60°. Tripropylcyclopropenyl,²²³ tricyclopropylcyclopropenyl,²²⁴ chlorodipropylcyclopropenyl,²²⁵ and chloro-bis-dialkylaminocyclopropenyl²²⁶ cations are among the most stable carbocations known, being stable even in water solution. The tri-tert-butylcyclopropenyl cation is also very stable.²²⁷ In addition, cyclopropenone and several of its derivatives are stable compounds,²²⁸ in accord with the corresponding stability of the tropones.²²⁹ The ring system 80 is nonalternant and the corresponding radical and anion, which do not have an aromatic duet, have electrons in antibonding orbitals, so that their energies are much higher. As with 58 and 62, the equivalence of the three carbon atoms in the triphenylcyclopropenyl cation has been demonstrated by ¹⁴C labeling experiments.²³⁰ The interesting dications 81 (R = Me or Ph) have been prepared,²³¹ and they too should represent aromatic systems of two electrons.²³²

2.K.ii. Systems of Four Electrons: Antiaromaticity

The most obvious compound in which to look for a closed loop of four electrons is cyclobutadiene (77).²³³ Hückel's rule predicts no aromatic character since 4 is not a number generated from 4n + 2. There is a long history of attempts to prepare this compound and its simple derivatives, and those experiments fully bear out Hückel's prediction. Cyclobutadienes display none of the characteristics that would lead us to call them aromatic, and there is evidence that a closed loop of four electrons is actually antiaromatic.²³⁴ If such compounds simply lacked aromaticity, we would expect them to be about as stable as similar nonaromatic compounds, but both theory and experiment show that they are much less stable.²³⁵ An antiaromatic compound may be defined as a compound that is destabilized by a closed loop of electrons.

Cyclobutadiene was first prepared by Pettit and co-workers.²³⁶ It is now clear that 77 and its simple derivatives are extremely unstable compounds with very short lifetimes (they dimerize by a Diels–Alder reaction; see 15–60) unless they are stabilized in some fashion, either at ordinary temperatures embedded in the cavity of a hemicarcerand²³⁷ (see the structure of a carcerand in Sec. 3.C.iii), or in matrices at very low temperatures (generally < 35 K). In either of these cases, the cyclobutadiene molecules are forced to remain apart from each other, and other molecules cannot get in. The structures of 77 and some of its derivatives have been studied a number of times using the low-temperature matrix technique.²³⁸ The ground-state structure of 77 is a rectangular diene (not a diradical), as shown by the (Ir) spectra of 77 and deuterated 77 trapped in matrices,²³⁹ as well as by a photoelectron spectrum.²⁴⁰Molecular orbital calculations agree.²⁴¹ The same conclusion was also reached in an elegant experiment in which 1,2-dideuterocyclobutadiene was generated. If 77 is a rectangular diene, the dideutero compound should exist as two isomers, as shown.

The compound was generated (as an intermediate that was not isolated) and two isomers were indeed found.²⁴² The cyclobutadiene molecule is not static, even in the matrices. There are two forms (77a and 77b) that rapidly interconvert.²⁴³ Note that there is experimental evidence that the aromatic and antiaromatic characters of neutral and dianionic systems are measurably increased via deuteration.²⁴⁴

There are some simple cyclobutadienes that are stable at room temperature for varying periods of time. These either have bulky substituents or carry certain other stabilizing substituents, such as seen in tri-tert-butylcyclobutadiene (83).²⁴⁵ Such compounds are relatively stable because dimerization is sterically hindered. Examination of the NMR spectrum of 82 showed that the ring proton (δ = 5.38) was shifted upfield, compared with the position expected for a nonaromatic proton, (e.g., cyclopentadiene). As will be seen in Section. 2.K.vi, this indicates that the compound is antiaromatic.

The other type of stable cyclobutadiene has two electron-donating and two electron-withdrawing groups,²⁴⁶ and is stable in the absence of water.²⁴⁷ An example is 83. The stability of these compounds is generally attributed to the resonance shown, a type of resonance stabilization called the push–pull or captodative effect,²⁴⁸ although it has been concluded from a PES that second-order bond fixation is more important.²⁴⁹ An X-ray crystallographic study of 83has shown²⁵⁰ the ring to be a distorted square with bond lengths of 1.46 Å and angles of 87° and 93°.

It is clear that simple cyclobutadienes, which could easily adopt a square planar shape if that would result in aromatic stabilization, do not in fact do so and are not aromatic. The high reactivity of these compounds is not caused merely by steric strain, since the strain should be no greater than that of simple cyclopropenes, which are known compounds. It is probably caused by antiaromaticity.²⁵¹

The cyclobutadiene system can be stabilized as a η⁴-complex with metals,²⁵² as with the iron complex 84 (see Chap 3), but in these cases electron density is withdrawn from the ring by the metal and there is no aromatic quartet. In fact, these cyclobutadiene–metal complexes can be looked upon as systems containing an aromatic duet. The ring is square planar,²⁵³ the compounds undergo aromatic substitution,²⁵⁴ and NMR spectra of monosubstituted derivatives show that the C-2 and C-4 protons are equivalent.²²⁹

Other systems that have been studied as possible aromatic or antiaromatic four-electron systems include the cyclopropenyl anion (86) and the cyclopentadienyl cation (87).²⁵⁵ With respect to 86, HMO theory predicts that an unconjugated 85 (i.e., a single canonical form) is more stable than a conjugated 86,²⁵⁶ so that 85 would actually lose stability by forming a closed loop of four electrons. The HMO theory is supported by experiment. Among other evidence, it has been shown that 88 (R = COPh) loses its proton in hydrogen-exchange reactions ~ 6000 times more slowly than 89 (R = COPh).²⁵⁷ Where R = CN, the ratio is ~ 10,000.²⁵⁸ This indicates that 88 are much more reluctant to form carbanions (which would have to be cyclopropenyl carbanions) than 89, which form ordinary carbanions. Thus the carbanions of 88 are less stable than corresponding ordinary carbanions. Although derivatives of cyclopropenyl anion have been prepared as fleeting intermediates (as in the exchange reactions mentioned above), all attempts to prepare the ion or any of its derivatives as relatively stable species have so far met with failure.²⁵⁹

In the case of 87, the ion has been prepared and shown to be a diradical in the ground state,²⁶⁰ as predicted by the discussion in Section 2.K.ii.²⁶¹ Evidence that 87 is not only nonaromatic, but is antiaromatic comes from studies on 90 and 92.²⁶² When 90 is treated with silver perchlorate in propionic acid, the molecule is rapidly solvolyzed (a reaction in which the intermediate 91 is formed; see Chapters 5 and 10). Under the same conditions, 92 undergoes no solvolysis at all; that is, 87 does not form. If 87 were merely nonaromatic, it should be about as stable as 91 (which of course has no resonance stabilization at all). The fact that it is so much more reluctant to form indicates that 87 is much less stable than 91. Note that under certain conditions, 91 can be generated solvolytically.²⁶³

The fact that 86 and 87 are not aromatic while the cyclopropenyl cation (80) and the cyclopentadienyl anion (58) is strong evidence for Hückel's rule since simple resonance theory predicts no difference between 86 and 80 or 87and 58 (the same number of equivalent canonical forms can be drawn for 86 as for 80 and for 87 as for 58).

2.K.iii. Systems of Eight Electrons

Cyclooctatetraene²⁶⁴ ([8]annulene, 78a) is not planar, but tub shaped,²⁶⁵ so it is neither aromatic nor antiaromatic, since both these conditions require overlap of parallel p orbitals. The reason for the lack of planarity is that a regular octagon has angles of 135°, while sp² angles are most stable at 120°. To avoid the strain, the molecule assumes a nonplanar shape, in which orbital overlap is greatly diminished.²⁶⁶ Single- and double-bond distances in 78 are, respectively, 1.46 and 1.33 Å, which is expected for a compound made up of four individual double bonds.²⁶⁵ The Jahn–Teller effect has been invoked to explain the instability of such antiaromatic compounds.²⁶⁷ The Jahn-Teller effect arises from molecular distortions due to an electronically degenerate ground state.²⁶⁸

The reactivity is also what would be expected for a linear polyene. Reactive intermediates can be formed in solution. Dehydrohalogenation of bromocyclooctatetraene at −100 °C has been reported, for example, and trapping by immediate electron transfer gave a stable solution of the [8]annulyne anion radical.²⁶⁹

The cyclooctadiendiynes 93 and 94 are planar conjugated eight-electron systems (the four extra triple-bond electrons do not participate), which NMR evidence show to be antiaromatic.²⁷⁰ There is evidence that part of the reason for the lack of planarity in 78 itself is that a planar molecule would have to be antiaromatic.²⁷¹ The cycloheptatrienyl anion (61) also has eight electrons, but does not behave like an aromatic system.¹⁶⁷ The bond lengths for a series of molecules containing the cycloheptatrienide anion have recently been published.²⁷² The NMR spectrum of the benzocycloheptatrienyl anion (95) shows that, like 82, 93, and 94, this compound is antiaromatic.²⁷³ A new anti-aromatic compound 1,4-biphenylene quinone (96) was prepared, but it rapidly dimerizes due to instability.²⁷⁴

2.K.iv. Systems of Ten Electrons²⁷⁵

There are three possible geometrical isomers of [10]annulene: the all-cis (97), the mono-trans (98), and the cis-trans-cis-cis-trans (79). If Hückel's rule applies, they should be planar. But it is far from obvious that the

molecules would adopt a planar shape, since they must overcome considerable strain to do so. For a regular decagon (97) the angles would have to be 144°, considerably larger than the 120° required for sp² angles. Some of this strain would also be present in 98, but this kind of strain is eliminated in 79 since all the angles are 120°. However, it was pointed out by Mislow²⁷⁶ that the hydrogen atoms in the 1 and 6 positions should interfere with each other and force the molecule out of planarity. Such configurational changes are not necessarily without cost energetically. It has been determined that configurational changes in [14]annulene, for example. requires Möbius antiaromatic bond shifting.²⁷⁷

Compounds 97 and 98 have been prepared²⁷⁸ as crystalline solids at −80 °C. The NMR spectra show that all the hydrogen atoms lie in the alkene region, and it was concluded that neither compound is aromatic. Calculations on 98suggest that it may indeed be aromatic, although the other isomers are not.²⁷⁹ It is known that the Hartree–Fock (HF) method incorrectly favors bond-length-alternating structures for [10]annulene, and aromatic structures are incorrectly favored by density functional theory. Improved calculations predict that the twist conformation is lowest in energy, and the naphthalene-like and heart-shaped conformations lie higher than the twist by 1.40 and 4.24 kcal mol⁻¹(5.86 and 17.75 kJ mol⁻¹), respectively.²⁸⁰ Analysis of ¹³C and ¹H NMR spectra suggest that neither is planar. However, the preparation of several compounds that have large angles, but that are definitely planar 10-electron aromatic systems, clearly demonstrate that the angle strain is not insurmountable. Among these are the dianion 99, the anions 100 and 101, and the azonine 102.²⁸¹ Compound 99²⁸² has angles of ~ − 135°, while 100²⁸³ and 101²⁸⁴have angles of ~ 140°, which are not very far from 144°. The inner proton in 101²⁸⁵ which is the mono-trans isomer of the all-cis 100 is found far upfield in the NMR (−3.5 δ). For 97 and 98, the cost in strain energy to achieve planarity apparently outweighs the extra stability that would come from an aromatic ring. Further emphasizing the delicate balance between these factors, it is known that the oxygen analogue of 102 (X = O, oxonin) and the N-carbethoxy derivative of 102 (X = CH) are nonaromatic and nonplanar, while 102 (X = N) is aromatic and planar.²⁸⁶ Other azaannulenes are known, including Vogel's 2,7-methanoazaannulene,²⁸⁷ as well as 3,8-methanoaza[10]annulene,²⁸⁸ and the alkoxy derivative of both.²⁸⁹ Calculations for aza[10]annulene concluded that the best olefinic twist isomer is 2.1 kcal mol⁻¹ (8.8 kJ mol⁻¹) more stable than the aromatic form,²⁹⁰ and is probably the more stable form.

So far, 79 from above has not been prepared despite many attempts. However, there are various ways of avoiding the interference between the two inner protons. The approach that has been most successful involves bridging the 1 and 6 positions.²⁹¹ Thus, 1,6-methano[10]annulene (103)²⁹² and its oxygen and nitrogen analoges 104²⁹³ and 105²⁹⁴ have been prepared, and they are stable compounds, are diatropic, and undergo aromatic substitution.²⁹⁵ For example, the perimeter protons of 103 are found at 6.9–7.3 δ, while the bridge protons are at −0.5 δ. The crystal structure of 103 shows that the perimeter is nonplanar, but the bond distances are in the range 1.37–1.42 Å.²⁹⁶ It has therefore been amply demonstrated that a closed loop of 10 electrons is an aromatic system, although some molecules that could conceivably have such a system are too distorted from planarity to be aromatic. A small distortion from planarity (as in 103) does not prevent aromaticity, at least in part because the σ orbitals so distort themselves as to maximize the favorable (parallel) overlap of p orbitals to form the aromatic 10-electron loop.²⁹⁷

In 106, where 103 is fused to two benzene rings in such a way that no canonical form can be written in which both benzene rings have six electrons, the aromaticity is diminished by annellation, as shown by the fact that the molecule rapidly converts to the more stable 107, in which both benzene rings can be fully aromatic²⁹⁸ (this is similar to the cycloheptatriene–norcaradiene conversions discussed in 18–32).

Molecules can sustain significant distortion from planarity and retain their aromatic character. 1,3-Bis(trichloroacetyl)homoazulene (108) qualifies as aromatic using the geometric criterion that there is only a small average deviation from the C–C bond length in the [10]annulene perimeter.²⁹⁹ The X-ray crystal structure shows that the 1,5-bridge distorts the [10]annulene π-system away from planarity (see the 3D model) with torsion angles as large as 42.2° at the bridgehead position, but 108 does not lose its aromaticity.

2.K.v. Systems of More Than Ten Electrons: 4n + 2 Electrons³⁰⁰

Extrapolating from the discussion of [10]annulene, larger 4n + 2 systems are expected to be aromatic if they are planar. Mislow²⁷⁶ predicted that [14]annulene (109) would possess the same type of interference as 79, although to a lesser degree. This is borne out by experiment. Compound 109 is aromatic (it is diatropic; inner protons at 0.00 δ, outer protons at 7.6 δ),³⁰¹ but is highly reactive and is completely destroyed by light and air in 1 day. X-ray analysis shows that although there are no alternating single and double bonds (the molecule is not planar).³⁰² A number of stable bridged [14]annulenes have been prepared³⁰³ [e.g., trans-15,16-dimethyldihydropyrene (110),³⁰⁴syn-1,6:8,13-diimino[14]annulene (111),³⁰⁵ and syn- and anti-1,6:8,13-bismethano[14]annulene (112 and 113)].³⁰⁶ The dihydropyrene (110, and its diethyl and dipropyl homologues) is undoubtedly aromatic: The π perimeter is approximately planar,³⁰⁷ the bond distances are all 1.39–1.40 Å, and the molecule undergoes aromatic substitution³⁰⁴ as well as being diatropic.³⁰⁸ The outer protons are found at 8.14–8.67 δ, while the CH₃ protons are at −4.25 δ. Other nonplanar aromatic dihydropyrenes are known.³⁰⁹ Annulenes 111 and 112 are also diatropic,³¹⁰ although X-ray crystallography indicates that the π periphery in 111 is not quite planar.³¹¹ In 113, the geometry of the molecule greatly reduces the overlap of the p orbitals at the bridgehead positions with adjacent p orbitals, and it is definitely not aromatic,³¹² as shown by NMR spectra³⁰⁶ and X-ray crystallography, from which bond distances of 1.33–1.36 Å for the double bonds and 1.44–1.49 Å for the single bonds have been obtained.³¹³ In contrast, all the bond distances in 111 are ~ 1.38–1.40 Å.³¹¹

Another way of eliminating the hydrogen interferences of [14]annulene is to introduce one or more triple bonds into the system, as in dehydro[14]annulene (114).³¹⁴ All five known dehydro[14]annulenes are diatropic, and 87 can be nitrated or sulfonated.³¹⁵ The extra electrons of the triple bond do not form part of the

aromatic system, but it simply exists as a localized bond. There has been a debate concerning the extent of delocalization in dehydrobenzoannulenes,³¹⁶ but there is evidence for a weak, but discernible ring current.³¹⁷3,4,7,8,9,10,13,14-Octahydro[14]annulene (116) has been prepared, for example, and the evidence supported its aromaticity.³¹⁸ This study suggested that increasing benzoannelation of the parent 116 led to a step-down in aromaticity, a result of competing ring currents in the annulenic system. Note that [12]annulyne has been prepared.³¹⁹

[18]Annulene (115) is diatropic:³²⁰ the 12 outer protons are found at ~ δ = 9 and the 6 inner protons at ~ δ = −3. X-ray crystallography³²¹ shows that it is nearly planar, so that interference of the inner hydrogen atoms is not important in annulenes this large. Compound 115 is reasonably stable, being distillable at reduced pressures, and undergoes aromatic substitutions³²² (Chapter 11). The C–C bond distances are not equal, but they do not alternate. There are 12 inner bonds of ~1.38 Å and 6 outer bonds of ~1.42 Å.³²¹ Compound 115 has been estimated to have a resonance energy of ~37 kcal mol⁻¹ (155 kJ mol⁻¹), similar to that of benzene.³²³

The known bridged [18]annulenes are also diatropic,³²⁴ as are most of the known dehydro[18]annulenes.³²⁵ The dianions of open and bridged [16]annulenes³²⁶ are also 18-electron aromatic systems,³²⁷ and there are dibenzo[18]annulenes.³²⁸

[22]Annulene³²⁹ and dehydro[22]annulene³³⁰ are also diatropic. A dehydrobenzo[22]annulene has been prepared that has eight CC units, is planar, and possesses a weak induced ring current.³³¹ In the latter compound, there are 13 outer protons at 6.25–8.45 δ and 7 inner protons at 0.70–3.45 δ. Some aromatic bridged [22]annulenes are known.³³² [26]Annulene has not yet been prepared, but several dehydro[26]annulenes are aromatic.³³³ Furthermore, the dianion of 1,3,7,9,13,15,19,21-octadehydro[24]annulene is another 26-electron system that is aromatic.³³⁴ Ojima and et al.³³⁵ prepared bridged dehydro derivatives of [26], [30], and [34]annulenes. All are diatropic. The same workers prepared a bridged tetradehydro[38]annulene,³³⁵ which showed no ring current. On the other hand, the dianion of the cyclophane, (117) also has 38 perimeter electrons, and this species is diatropic.³³⁶

There is now no doubt that 4n + 2 systems are aromatic if they can be planar, although 97 and 113 among others, demonstrate that not all such systems are in fact planar enough for aromaticity. Both 109 and 111 prove that absolute planarity is not required for aromaticity, but that aromaticity decreases with decreasing planarity.

The NMR spectrum of 118 (called kekulene) showed that in a case where electrons can form either aromatic sextets or larger systems, the sextets are preferred.³³⁷ There was initial speculation that kekulene might be superaromatic, that is, it would show enhanced aromatic stabilization. Calculations suggest that there is no enhanced stabilization.³³⁸ The 48 π electrons of 118 might, in theory, prefer structure 118a, where each ring is a fused benzene ring, or 118b, which has a [30]annulene on the outside and an [18]annulene on the inside. The NMR spectrum of this compound shows three peaks at δ = 7.94, 8.37, and 10.45 in a ratio of 2:1:1. Examination of the structure shows that 118 contains three groups of protons. The peak at 7.94 δ is attributed to the 12 ortho protons and the peak at 8.37 δ to the six external para protons. The remaining peak comes from the six inner protons. If the molecule preferred 118b, this peak should be upfield, probably with a negative δ, as in the case of 115. The fact that this peak is far downfield indicates that the electrons prefer to be in benzenoid rings. Note that in the case of the dianion of 117, the opposite situation prevails. In this ion, the 38-electron system is preferred even though 24 of these must come from the six benzene rings, which therefore cannot have aromatic sextets.

Phenacenes are a family of “graphite ribbons,” where benzene rings are fused together in an alternating pattern. Phenanthrene is the simplest member of this family and other members include the 22 electron system picene (119), the 26 electron system fulminene (120) and the larger member of this family, the 30 electron [7]phenancene, with seven rings (121).³³⁹ In the series benzene to heptacene, reactivity increases although acene resonance energies per π electron are nearly constant. The inner rings of the “acenes” are more reactive, and calculations showed that those rings are more aromatic than the outer rings, and are even more aromatic than benzene itself.³⁴⁰ N-Heteroacenes are also known.³⁴¹

A super-ring molecule is formed by rolling a polyacene molecule into one ring with one edge benzene ring folding into the other. These are called cyclopolyacenes or cyclacenes.³⁴² Although the zigzag cyclohexacenes (122) are highly aromatic (this example is a 22 electron system), the linear cyclohexacenes (e.g., the 24 electron 123) are much less aromatic.³⁴³ It is possible to deform an acene by attaching bulky substituents to its periphery by single covalent bonds. The presence of these substituents, which often leads to twisting of torsion angles, is usually easier than distortion of bond angles or C-C bond lengths. Such compounds are called twisted acenes.³⁴⁴

2.K.vi. Systems of More Than 10 Electrons: 4n Electrons²⁴⁹

As seen in Section 2.K.ii, these systems are expected to be not only nonaromatic, but also antiaromatic. The [12]annulene (124) has been prepared.³⁴⁵ In solution, 124 exhibits rapid conformational mobility (as do many other annulenes),³⁴⁶ and above −150°C in this particular case, all protons are magnetically equivalent. However, at −170°C the mobility is greatly slowed and the three inner protons are found at ~ 8 δ while the nine

outer protons are at ~ 6 δ. Interaction of the ‘internal’ hydrogen atoms in annulene (124) leads to nonplanarity. Above −50°C, 124 is unstable and rearranges to 125. Several bridged and dehydro[12]annulenes are known, for example, 5-bromo-1,9-didehydro[12]annulene (126),³⁴⁷ cycl[3.3.3]azine (127),³⁴⁸s-indacene (128),³⁴⁹ and 1,7-methano[12]annulene (129).³⁵⁰s-Indacene is a planar, conjugated system perturbed by two cross links, and studies showed that the low-energy structure has localized double bonds. In these compounds, both hydrogen interference and conformational mobility are prevented. In 127–129, the bridge prevents conformational changes, while in 126the bromine atom is too large to be found inside the ring. The NMR spectra show that all four compounds are paratropic, the inner proton of 126 being found at 16.4 δ. The dication of 112³⁵¹ and the dianion of 103³⁵² are also 12-electron paratropic species. An interesting 12-electron [13]annulenone has recently been reported, 5,10-dimethyl[13]annulenone (130). This annulenone is the first monocyclic annulene larger than tropane,³⁵³ and a linearly–fused benzodehydro[12]annulene system has been reported.³⁵⁴

The results for [16]annulene are similar. The compound was synthesized in two different ways,³⁵⁵ both of which gave 131, which in solution is in equilibrium with 132. Above −50 °C there is conformational mobility, resulting in the magnetic equivalence of all protons, but at −130 °C the compound is clearly paratropic: There are 4 protons at 10.56 δ and 12 at 5.35 δ. In the solid state, where the compound exists entirely as 131, X-ray crystallography³⁵⁶shows that the molecules are nonplanar with almost complete bond alternation: The single bonds are 1.44–1.47 Å and the double bonds are 1.31–1.35 Å. A number of dehydro and bridged [16]annulenes are also paratropic,³⁵⁷ as are [20]annulene,³⁵⁸ and [24]annulene.³⁵⁹ However, a bridged tetradehydro[32]annulene was atropic.³³³

Both pyracyclene (133),³⁶⁰ which because of strain is stable only in solution, and dipleiadiene (134)³⁶¹ are paratropic, as shown by NMR spectra. These molecules might have been expected to behave like naphthalenes with outer bridges, but the outer π frameworks (12 and 16 electrons, respectively) constitute antiaromatic systems with an extra central double bond. With respect to 133, the 4n + 2 rule predicts pyracylene to be “aromatic” if it is regarded as a 10-π-electron naphthalene unit connected to two 2-π-electron etheno systems, but “antiaromatic” if it is viewed as a 12-π-electron cyclododecahexaene periphery perturbed by an internal cross-linked etheno unit.³⁶² Recent studies have concluded on energetic grounds that 133 is a “borderline” case, in terms of aromaticity–antiaromaticity character.³⁶⁰ Dipleiadiene appears to be antiaromatic.³⁶¹

The fact that many 4n systems are paratropic even though they may be nonplanar and have unequal bond distances indicates that if planarity were enforced, the ring currents might be even greater. The NMR spectrum of the dianion of 110³⁶³ (and its diethyl and dipropyl homologues)³⁶⁴ effectively illustrate this point. Recall that in 110, the outer protons were found at 8.14–8.67 δ with the methyl protons at −4.25 δ. For the dianion, however, which is forced to have approximately the same planar geometry, but now has 16 electrons, the outer protons are shifted to about −3 δ while the methyl protons are found at ~ 21 δ, a shift of ~ 25 δ! A converse shift was made when [16]annulenes that were antiaromatic were converted to 18-electron dianions that were aromatic.²⁸² In these cases, the changes in NMR chemical shifts were almost as dramatic. Heat-of-combustion measures also show that [16]annulene is much less stable than its dianion.³⁶⁵ It has also been reported that the fluorenyl cation shows substantial destabilization, suggesting that it is an antiaromatic species.³⁶⁶

It seems clear that 4n systems will be at a maximum where a molecule is constrained to be planar (as in 86 or the dianion of 110) but, where possible, the molecule will distort itself from planarity and avoid equal bond distances in order to reduce. In some cases (e.g., cyclooctatraene), the distortion and bond alternation are great enough to be completely avoided. In other cases, (e.g., 124 or 131), it is apparently not possible for the molecules to avoid at least some p orbital overlap. Such molecules show evidence of paramagnetic ring currents, although the degree of is not as great as in molecules (e.g., 86 or the dianion of 110).

The concept of “Möbius aromaticity” was conceived by Helbronner in 1964,³⁶⁷ when he suggested that large cyclic [4n]annulenes might be stabilized if the π orbitals were twisted gradually around a Möbius strip. This concept is illustrated by the diagrams labeled Hückel, which is a destabilized [4n] system, in contrast to the Möbius model, which is a stabilized [4n] system.³⁶⁸ Zimmerman generalized this idea and applied the “Hückel–Möbius concept” to the analysis of ground-state systems [e.g., barrelene (135)].³⁶⁹ In 1998, a computational reinterpretation of existing experimental evidence for (CH)₉⁺ as a Möbius aromatic cyclic annulene with 4n π-electrons was reported.³⁷⁰ This reversal of [4n]annulene antiaromaticity has been demonstrated by stacking rings into a superphane.³⁷¹ A superphane is a sixfold bridged cyclophane with all arene positions in the corresponding dimer taken up by ethylene spacers.³⁷² A recent computational study predicted several Möbius local minima for [12], [16], and [20]annulenes.³⁷³ A twisted [16]annulene has been prepared and calculations suggested it should show Möbius aromaticity.³⁷⁴ High-performance liquid chromatography (HPLC) separation of isomers gave 136, and the authors concluded it is Möbius aromatic. The synthesis and study of molecules that demonstrate Möbius aromaticity continues to be an area of interest.³⁷⁵