768 |
ARYNES |
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∆H (kcal mol-1) 157.0 |
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160.3 |
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7.4 |
152.9 |
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19.8 |
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25.2 |
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28.5 |
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17.8 |
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138.0 |
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52 |
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8.5 |
135.1 |
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129.5 |
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28 |
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16 |
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65 |
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Figure 16.4. The energy profiles of the Bergman cyclization of 16 and 65 as measured by Roth et al.60,96
structure of 52). The effect of benzannellation on the energetics of the Bergman cyclization (65 ! 52) has been investigated in the gas phase by Roth et al. (Fig. 16.4).96 The barrier of 25 kcal/mol for cyclization of 65 is lower than for (Z)-16. This value is in excellent agreement with the activation parameters determined by Grissom et al.97 for the reactions 65 ! 52 (Ea ¼ 25.1 kcal/mol in solution). The reaction enthalpy for cyclization of the benzannellated system is higher, that is the reaction is more endothermic, which has been rationalized by the smaller amount of resonance energy released by formation of the second six-membered ring in naphthalene compared to benzene.96 Accordingly, the barrier for the reverse (ring-opening) reaction 52 ! 65 is lower than that for p-benzyne 28 (19.8 kcal/mol).96
In 1,5-naphthyne (53) the separation of A and S orbitals is larger than in 52, since in the former there is no through-space interaction counteracting the through-bond coupling.88 Accordingly, the singlet–triplet energy splitting is slightly enlarged in 53.
. .
52
53
Formula 16.5
Myers et al.98 were able to trap 1,5-naphthyne (53), which is formed in solution from 1,2,6,7-tetradehydro[10]annulene (66) even at 40 C.98 The intermediate
formation of the naphthyne was confirmed by formation of the 1,5-dideuterated product in deuterated solvents (Scheme 16.20). In a similar fashion, the 2,6-isomer 58 could be generated by a cyclization cascade from (Z,Z)-deca-3,7-diene-1,5,9- triene (67) by Bergman and co-workers.99
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H(D) |
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170 − 190 °C |
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+ [H/D] |
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H(D) |
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58 |
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67 |
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H(D) |
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+ [H/D] |
− 40 °C |
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66 |
. |
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H(D) |
53 |
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Scheme 16.20. Formation of naphthynes 53 and 58 by cycloaromatization of 66 and 67.98,99
The remaining two isomers 54 and 59 have not yet been observed experimentally. According to calculations, the singlet–triplet splitting in 59 is comparably large ( 3 kcal/mol), while both states are essentially degenerate in 54.88 Such
‘‘zig–zag couplings’’ for ‘‘W’’-type arrangements of orbitals are well known in NMR100 and ESR spectroscopy.88,101
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54 |
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59 |
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Formula 16.6 |
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4.2. Didehydroindenes
Interest in the didehydroindenes has been facilitated by the discovery of the neocarcinostatin cytostatics, that are closely related to the endiyne antitumor drugs (Scheme 16.21).102
770 ARYNES |
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OMe |
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H |
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O |
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OMe |
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MeHN |
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OH |
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OMe O |
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Scheme 16.21. Activation of neocarcinostatin (thiol independent pathway; see Ref. 7f for details).
Cycloaromatization of the cyclic eneyneallene (68) produces the 1,5-didehydroin- dene biradical 69, that abstracts hydrogen atoms from the DNA strand in analogy to the calicheamicins (cf. Section 3.3).
.
.
Formula 16.7
The prototype of this reaction is the Myers–Saito reaction, the rearrangement of eneyneallene (Z)-hepta-1,2,4-triene-6-yne (70) to a,3-didehydrotoluene (71). This C2 C7 cyclization yields a benzylic p-conjugated s,p-biradical and is therefore exothermic by 15 3 kcal/mol (Fig. 16.5).103 The reaction barrier was determined to be 22 kcal/mol.103 Also known in literature is the alternative C2 C6cyclization (Schmittel cyclization), which generates a less stable fulvenic structure 72.104 According to calculations, the Schmittel cyclization is endothermic by 10– 19 kcal/mol with an activation barrier of 30–35 kcal/mol.105 Replacing the
acetylenic hydrogen atoms by sterically demanding substituents, however, favors the C2 C6 over C2 C7 cyclization.104,105 Phenyl groups also reverse
the energetics by benzylic stabilization in the transition state of the Schmittel
E (kcal mol-1)
30 − 35
C2C6
Schmittel
10 − 19
H .
H
.
H
72
Figure 16.5. Myers–Saito versus Schmittel cyclization.103–105
cyclization.104,105 The activation enthalpy for the cyclization 68 ! 69 was calculated to be 18 kcal/mol; the reaction is slightly exothermic by 1 kcal/mol (in contrast to acyclic system 71, 69 does not profit from benzylic stabilization).106 The interesting a,3-didehydrotoluene biradical 71 has not yet been matrix isolated and structurally characterized. However, it could be shown experimentally by CID measurements in the gas phase that 71 (in contrast to a,2- and a,4-didehy- drotoluene) possesses a singlet ground state.107 According to these experiments the lowest triplet state is 3 kcal/mol higher in energy,107 in reasonable agreement with photoelectron spectroscopic data of Chen and co-workers (5 kcal/mol)108 and quan-
tum chemical calculations.109
The first isolation of a derivative of 71 was reported by Sander et al. in 1998.110 Irradiation of quinone diazide (73) with l > 475 nm in an argon matrix at 10 K quantitatively yields 2,6-dimethylcyclohexa-2,5-diene-1-one-4-ylidene (74). Short wavelength irradiation (l > 360 nm) converts 74 into the substituted a,3- didehydrotoluene derivative 75 (Scheme 16.22). Upon prolonged irradiation 76
and (presumably) 77 are formed by Myers cycloreversion. No evidence was found for the formation of bicyclic 78.110
Didehydroindenes have been studied in detail computationally.111 Relative enthalpies of all possible isomers are summarized in Table 16.4. The three isomers bearing the formal C C bond within the six-membered ring hardly differ in their stability and singlet–triplet gaps. This finding is in accordance with the fact that indene (in contrast to naphthalene) displays essentially no bond length alternation within the six-membered ring.111 The enthalpy of formation of the highly strained
772 |
ARYNES |
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OH |
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hν (> 475 nm) |
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hν (> 360 nm) |
CH2 |
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− N2 |
.. |
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. 75 |
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N2 |
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74 |
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73 |
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CH2 |
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78 |
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77 |
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76 |
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Scheme 16.22. The first direct detection of a derivative of a,3-didehydrotoluene.110
5,6-didehydroindene (92) is 16 kcal/mol higher. In close analogy to the corresponding naphthynes 51 and 56, the singlet–triplet gaps of 80 and 84 are significantly larger than in the 4,5-didehydroindene 90.111
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80 |
84 |
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90 |
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Formula 16.8 |
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TABLE 16.4. Relative Enthalpies (H298) and Singlet–Triplet Splittings |
of the Didehydroindenes |
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Isomer |
No. |
E(singlet) |
E(triplet) |
ESTa |
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1,2 |
79 |
0.1 |
30.2 |
30.1 |
1,3 |
80 |
13.8 |
26.6 |
13.0 |
1,4 |
81 |
18.3 |
26.2 |
7.9 |
1,5 |
69 |
21.4 |
29.0 |
7.7 |
1,6 |
82 |
27.0 |
27.5 |
0.4 |
2,3 |
83 |
0.5 |
30.2 |
29.8 |
2,4 |
84 |
14.2 |
26.9 |
12.9 |
2,5 |
85 |
28.1 |
27.7 |
0.3 |
2,6 |
86 |
26.0 |
27.9 |
1.9 |
3,4 |
87 |
0.0 |
30.6 |
30.6 |
3,5 |
88 |
28.0 |
27.8 |
0.2 |
3,6 |
89 |
26.3 |
27.5 |
1.2 |
4,5 |
90 |
27.1 |
28.6 |
1.5 |
4,6 |
91 |
27.1 |
28.0 |
0.8 |
5,6 |
92 |
15.7 |
34.9 |
19.3 |
a Calculated as difference of the singlet and triplet BSEs [CASPT2/cc-pVDZ þ ZPE(BPW91/cc-pVDZ)]. See Ref. 111. All values are in kilocalories per mole.
Apart from the 1,5 isomer, there is experimental evidence only for the intermediate formation of 1,2-didehydroindane (93), the saturated analogue of 79. The FVP of nona-1,3,8-triyne (94) yields indane (95) and indene (96), which is formed from 95 by loss of H2.112 Results from isotopic labeling suggest an unusual (1,3- diyne þ alkyne)[2 þ 4]-cycloaromatization resembling a Diels–Alder reaction, forming 1,2-didehydroindane (93, Scheme 16.23).112
600 °C |
|
+ 2 [H] |
94 |
93 |
95 |
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– H2 |
96
Scheme 16.23. Thermolysis of 94 results in formation of indane (95), presumably via intermediate formation of didehydroindane (93).112
5. HETEROCYCLIC ARYNES
Despite the fact that the history of hetarynes is older than that of the benzynes (cf. 2), physical data on these compounds are scarce. Numerous trapping experiments furnished evidence for the formation of biradicaloid intermediates in the field of five-membered heterocycles (didehydrofurans, -thiophenes, and -pyrroles).113 Direct spectroscopic data on these species, however, do not exist, which may be attributable to the increased ring strain in the five-membered o-arynes, associated with a strong tendency to undergo ring-opening reactions.
Investigations of six-membered heteroarynes concentrate on didehydropyridines, which will be dealt with exclusively in this section. The influence of the nitrogen lone pair on the structural and electronic properties of the benzynes was investigated by Cramer and Debbert.114 Relative energies of the six isomeric pyridynes
and their singlet–triplet splittings are summarized in Table 16.5.
In agreement with prior calculations26u,115 at low levels of theory, it could be
shown that 3,4-pyridyne (101) is significantly more stable than the 2,3-isomer (97).114 The formal C C triple bond length is similar in 4 and 101, while it is
markedly elongated in 97 (4: 124.1 pm; 101: 124.8 pm; 97: 126.7 pm; B3LYP/ cc-pVTZ).83,114 In addition, the singlet–triplet gap of 4 and 101 is comparable,
whereas it is reduced by 16 kcal/mol in 97. This difference is caused by a
774 ARYNES
TABLE 16.5. Relative Energies and Singlet–Triplet Splittings of the Six Pyridynes
Isomer |
No. |
E(singlet) |
E(triplet) |
ESTa |
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2,3 |
97 |
7.1 |
21.7 |
14.6 |
2,4 |
98 |
1.2 |
24.5 |
23.3 |
2,5 |
99 |
11.3 |
24.0 |
13.0 |
2,6 |
100 |
17.5 |
14.9 |
1.2 |
3,4 |
101 |
0.0 |
33.5 |
32.9 |
3,5 |
102 |
14.7 |
28.2 |
14.2 |
a Calculated as the difference of the singlet and triplet BSEs [CASPT2(8,8)/cc-pVDZ//CASSCF(8,8)/cc- pVDZ)]. See Ref. 114.
cumulative effect of both, destabilization of the singlet ground state, and stabilization of the triplet state of 97, as is evident from the calculated BSEs. The triplet state gains stability from the efficient delocalization to the third center. The calculated 14N hyperfine coupling constant of 37 G in 2,3-pyridyne is significantly larger than in the 2,4 and 2,5 isomers with 32 and 31 G, respectively. On the other hand, the singlet state of 97 is destabilized by an unfavorable three-center, four-electron interaction, which makes the major contribution to the difference in EST between 101 and 97. In addition, an anomeric effect of the nitrogen lone pair on the vicinal C C bonds is likely to be operative in 97, which leads to an elongation of the formal triple bond and causes destabilization and an increase of the biradical character.114
In 1972 Berry and co-worker116 detected 3,4-pyridyne (101) by MS. Trapping experiments also provided evidence for the existence of this intermediate, although the chemistry of 101 differs considerably from that of o-benzyne.113 Thus, neither anthracene113a nor dimethylfulvene117 form Diels–Alder adducts with 101. Nam and Leroi118 were able to generate 101 in nitrogen matrices at 13 K and characterized it by IR spectroscopy. Irradiation of 3,4-pyridinedicarboxylic anhydride (103) with l > 340 nm results in formation of 101, which upon short wavelength photolysis (l > 210 nm) fragments to buta-1,3-diyne (104) and HCN, and to acetylene (105) and cyanoacetylene (106, Scheme 16.24). The assignment of an intense
O |
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+ |
H |
H |
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hν (> 340 nm) |
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104 |
O |
hν (> 210 nm) |
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− CO, CO2 |
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Scheme 16.24. Generation and photofragmentation of 101 in a nitrogen matrix at 13 K.118
absorption at 2085 cm 1 to the C C stretching mode in 101118 might have to be revised in view of Radziszewski’s reinterpretation of the o-benzyne spectrum; ketene structures are apparently formed in this case as well (cf. Section 2.1).
2,3-Didehydropyridine (97) is less well investigated, and the existence of this intermediate is not yet established definitively. Aryne 97 has been postulated as an intermediate in the gas-phase pyrolysis of 2,3-pyridinedicarboxylic anhydride (107) at 600 C, which finally yields b-ethinyl acrylonitrile (108).119 Indirect evidence stems from trapping experiments with benzene and thiophene.113e Photolysis of matrix isolated 107 does not produce 97 (Scheme 16.25). Nam and Leroi120
O |
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600 °C |
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600 °C |
O |
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− CO, CO2 |
N |
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N |
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107 O |
97 |
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hν (> 300 nm) H |
N |
H |
− CO |
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H |
O
hν (> 300 nm)
− CO2 hν (> 300 nm) − CO
N
(E )-108
H
N+ C−
hν (> 210 nm)
O |
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hν (> 340 nm) |
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O − CO |
H |
N |
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− |
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C |
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109 |
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(Z )-108 |
107 |
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Scheme 16.25. 2,3-Pyridyne was postulated as an intermediate in the gas-phase pyrolysis of 107, finally forming 108.119 Direct proof for the existence of this species has not yet been
achieved. The above reaction scheme for the photolysis of 107 in a nitrogen matrix at 13 K was suggested by Nam and Leroi.120
suggested that loss of CO2 leads initially to the 3-acyl-2-pyridyl biradical, which ring opens to 109 significantly faster than the second radical center at the aromatic ring is formed by CO release.
So far the three isomeric m-pyridynes have eluded experimental observation,83a
although the properties of 98, 100, and 102 are of some interest from a theoretical point of view.114
776 ARYNES
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. |
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. |
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N |
N |
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N |
100 |
102 |
|
98 |
Formula 16.9
Isomer 100 is the least stable of all six pyridynes and its singlet and triplet state are essentially degenerate. It is less stable than the singlet ground state of ortho-isomer 101 by 21 kcal/mol.114 The structural flexibility of 100 is even more pronounced than in the case of the other m-arynes. In addition to monoand bicyclic structures
analogous to 13 and 18, an allylic structure with a widened C2 N C6 angle is found depending on the level of theory applied.83,114,115d The 3,5-isomer (102),
which lies energetically above 101 by 15–18 kcal/mol, is the second least stable pyridyne. The singlet–triplet gap of 102 is 18 kcal/mol, still below that of m- benzyne (13).114 The unprecedented properties of the m-pyridynes, and in particular of 100, result from a strong s-allylic interaction, as schematically depicted in Scheme 16.26.114
Scheme 16.26. s-Allylic interaction of the lone pair (n) at the nitrogen atom with the bonding (a1) and antibonding (b2) combination of the p orbitals in 100 and 102. Because of the stronger overlap, the HOMO and LUMO in 100 are essentially degenerate, which results
in a very small singlet–triplet gap. In 102 EST is decreased by only 3 kcal/mol compared to 13, since the structure can more easily distort to avoid destabilizing interactions.46,114 Note
that antibonding orbital interactions are always stronger than bonding, so that both structures are destabilized relative to 13.
2,4-Pyridyne (98) is the most stable of the three isomers, and, in contrast to 100 and 102, has a higher preference for the singlet ground state than 13. This change suggests the participation of nitrilium ion structure 98B and possibly 98C in the resonance hybrid, which is also evident from the shortening of the N C2 bond compared to the N C6 bond.
. |
− |
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− |
.. |
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.. |
.. |
. |
+ |
+ |
.. |
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N |
N |
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N |
98A |
98B |
|
98C |
Formula 16.10
An interesting route to 98 was suggested by Cramer et al.114 cyclization of isonitrile 110 could lead to 98 in a rearrangement analogous to the Bergman cyclization. The activation enthalpy for the only slightly exothermic reaction was estimated at 18 kcal/mol. However, this novel access to m-arynes could not be realized experimentally so far.
H N C− |
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+ |
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. |
H |
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N |
110 |
H |
98 |
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Formula 16.11
A three-center interaction similar to that in m-pyridynes 100 and 102 (Scheme 16.26) results in substantial stabilization in the two-electron case. 3,5- Didehydrophenyl cation (111), the classic example121 for ‘‘in-plane aromaticity,’’122 is the global minimum of the C6H3þ hypersurface.123 Remarkably, the
+ |
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111 |
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112 |
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113 |
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D3h |
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C2v |
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115 |
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