Reactive Intermediate Chemistry

748 ARYNES

− HBr

N

Br

17

− HBr

+ HNMe2

N

18

Scheme 16.7. From the observed trapping chemistry Washburn et al.38 concluded that the bicyclic intermediate 18 is formed instead of biradical 13. The question of whether 18 exists has been the subject of some controversy until recently.

The first spectroscopic evidence for a derivative of 13 was presented by Bucher et al.39 in 1992, who were able to isolate 2,4-didehydrophenol (19) in cryogenic matrices (Scheme 16.8). Irradiation of matrix isolated quinone diazide (20) with light of wavelength l ¼ 432 10 nm yields carbene (21), which is

Scheme 16.8. Didehydrophenol (19) was the first derivative of 13 that could be isolated in an argon matrix at 8 K. Comparison of measured and calculated spectra supports the assignment to a monocyclic structure 19. Evidence for bicyclic isomer 22 was not found. In contrast to 19, derivative 23 can be photochemically converted into carbene 24.39

photochemically converted into didehydrophenol (19) by long wavelength irradiation (l ¼ 575 10 nm). The existence of an OH group in 19 was confirmed by isotopic labeling using [D]1-20.39 Evidence for a bicyclic isomer 22 was not found.40 Benzannellated didehydrophenol (23) tautomerizes photochemically to carbene (24), in contrast to didehydrophenol (19), which yields ring-opened products of unknown constitution upon irradiation.39

14

Scheme 16.9. The matrix isolation and IR spectroscopic characterization of 13 was achieved starting from four different precursors.41,42

The isolation of the parent m-benzyne (13) in a cryogenic matrix was finally achieved in 1996 starting from diacetyl peroxide (25) as a thermal source and m-p-cyclophane-9,10-dione (26) as a photochemical precursor (Scheme 16.9).41 In recent work, the IR measurements were extended to the far infrared (FIR) region (>200 cm 1) and additional starting materials were used.42 In particular, it was shown that pyrolysis of 1,3-diiodobenzene at 600 C gives good yields of m- benzyne, together with (Z)- and (E)-hex-3-ene-1,5-diyne (16), the latter being formed exclusively at temperatures >650 C, in accordance with the earlier results obtained by Fisher and Lossing.12 The FVP of 1,3-dinitrobenzene also yields small amounts of 13.42 By using these four different routes to m-benzyne, all of the more intense IR absorptions of 13 were unambiguously identified. The IR spectrum of the perdeuterated isotopomer [D]4-13 was also obtained.42

The vibrational spectrum of 13 is nicely reproduced by quantum chemical calculations at the CCSD(T) level of theory,42 whereas density functional theory (DFT) shows a variable performance for 13 depending on the functional employed.43–46 This caution holds especially for the distance between the radical

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TABLE 16.1. Calculated Equilibrium Distances r(C1C3) of the Radical Centers in m-Benzynea

a References 44 and 46; distances r(C1C3) in picometers.

b Lowest energy structure calculated for (V)B3LYP/cc-pVTZ optimized geometries with constrained distances r(C1C3).

centers and the question of whether the matrix isolated species can also be assigned to the bicyclic structure 18. In more recent theoretical and experimental investigations, it was shown beyond any doubt that 13 has a monocyclic structure with a distance of 205 5 pm between the radical centers (Table 16.1).44,45 Nevertheless, the potential energy surface along the ‘‘cyclization coordinate’’ is very flat. Despite

the significant distance of the radical centers the biradical character of 13 is low (19–32%, depending on the definition of this quantity).26q,44 The electronic struc-

ture of 13 is most appropriately described as a s-allylic system, in which primarily the s*(C H) orbital, located between the dehydrocarbons, participates in the interaction of the radical lobes. Negative-ion photoelectron spectroscopy (NIPES) experiments also support a monocyclic structure for m-benzyne, although the spectra of 13 are considerably more complex than in the case of the ortho and para-isomers.22 The singlet–triplet energy splitting was determined to be 21.0 0.3 kcal/mol, confirming the low biradical character of 13.22

Scheme 16.10. The most probable pathways for the 13 ! 16 rearrangement.42

The mechanism of the rearrangement of m-benzyne (13) to hex-3-ene-1,5-diyne (16) has been elucidated recently.42 Possible isomerization pathways include ring opening to a vinylidene 27 with subsequent hydrogen-shift or rearrangement

to the para-isomer 28 followed by retro-Bergman reaction (Scheme 16.10, and Section 2.3).42,47 Experimental data obtained by Zewail and co-workers33 using

femtosecond time-resolved spectroscopy with mass spectrometric detection on the photolysis of 1,2-, 1,3-, and 1,4-dibromobenzene were interpreted by the authors in terms of a rapid equilibrium between o-, m-, and p-benzyne via quantum mechanical tunneling of hydrogen atoms, from which the para-isomer reacts to the entropically favored enediyne 16. Investigations by Sander et al.,42 however, favor an alternative mechanism of direct ring opening of 13. According to DFT calculations the vinylidene (27) does not occupy a stationary point on the potential energy surface, and ring opening and hydrogen migration occur in one step. At the

the G2M level of theory, the latter reaction requires an activation enthalpy of 60–61 kcal/mol.9b,33 The rearrangement of 13 to 30 requires 72 kcal/mol (B3LYP),42 whereas the ring opening of 18 to give biradical 29 has not yet been discussed in the literature. Rearrangement of m- to o-benzyne (4) has an activation enthalpy of 56 kcal/mol at the G2M level, although it is not entirely clear, whether

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this reaction leads initially to intermediate 9 (cf. Scheme 16.5).9b,33 Since no o- benzyne is observed under FVP conditions at 600 C, hydrogen scrambling in m- benzyne seems to be less likely than an alternative lower energy pathway (e.g., 13 ! [27] ! 16 or 13 ! [18] ! 29 ! 16). The rearrangment 13 ! 16 could also be induced photochemically.42

In summary, structure and vibrational spectrum of m-benzyne have been clarified during the last years. The (surprisingly) large variability of different quantum chemical methods in accounting for the structure and properties of 13 makes a more detailed exploration of intramolecular rearrangements of m-benzyne at more sophisticated (and coherent) levels of theory desireable. Even more complex appears to be the study of the intermolecular chemistry of 13. Almost nothing is known about thermal or photochemical reactions of m-benzyne with atoms or small molecules. A method for the investigation of (charged) m-benzyne derivatives in the gas phase using FT ion cyclotron resonance MS has recently been described by

¨ 48 48

Kenttamaa and co-workers (distonic ion approach). It could be shown that

the reactivity of m-benzyne is reduced compared to that of the phenyl radical because of strong coupling of the formally unpaired electrons. In addition, it was demonstrated that charged derivatives of 13 are reactive towards electrophiles and nucleophiles.48 Further insight into the intraand intermolecular reactivity of m- arynes can be expected in the near future, although many technical problems (concerning both experiment and theory) have to be solved, before the chemistry of these compounds can be completely clarified.

2.3. The p-Benzyne Story

Experimental access to p-benzyne 28 turned out to be even more difficult than to the meta-isomer 13. Pyrolysis of 1,4-diiodobenzene results in exclusive formation of hex-3-ene-1,5-diyne 16.12 Berry’s attempt to generate 28 by photoinitiated decomposition of benzene diazonium-4-carboxylate in the gas phase gave dubious results.34 Although the authors postulated the formation of 28, a lifetime of >2 min was measured for the product observed. Such a lifetime is incompatible with a reactive biradical, in particular since the lifetime of orthoand meta-isomers 4 and 13 are reported to be in the order of milliseconds and microseconds, respectively.34

Despite some earlier publications pointing out the intermediate formation of para-arynes,49 28 came into the focus of organic chemistry not before the classic experiments of Jones and Bergman in 1972.50 The authors observed that 1,6- [D]2-(Z)-hex-3-ene-1,5-diyne (16) rapidly reacts to a mixture of 3,4-[D]2- and 1,6-[D]2-16 at 300 C. The fact that no 1,3-[D]2- or 1,4-[D]2-16 is formed can only be explained by presumption of a cyclic, symmetrical intermediate (Scheme 16.11).50 Numerous trapping experiments supported the hypothesis of the thermal formation of p-benzyne from (Z)-16. In CCl4, for example, thermolysis of the enediyne yields 1,4-dichlorobenzene.50,51 The possibility of an alternative C1 C5 cyclization of enediyne 16 yielding fulvenediyl 30 was recently proposed by Schreiner and co-workers.52 However, the reaction is endothermic by 40 kcal/ mol, and the cyclization barrier amounts to 42 kcal/mol.52 Still, an experimental

1,3-[D]2-(Z )-16

Scheme 16.11. The Bergman cyclization.50

realization of this cyclization might be facilitated by adding sterically demanding substituents to the alkyne termini.53

While the majority of trapping experiments favors a biradicaloid structure, evidence for a bicyclic intermediate (butalene, 31) was also found.54 Breslow et al.54 reported the formation of 31 (the possible existence of which had been pointed out by Dewar before55) upon dehydrohalogenation of 3-chloro[2.2.0]bicyclohexadiene

D

Ph

Scheme 16.12. Indirect evidence for the formation of butalene upon dehydrohalogenation of 3-chlorobicyclo[2.2.0]hexadiene.52

(Scheme 16.12). The bicyclic nature of the intermediate was inferred from the observed Diels–Alder type reactivity with activated dienes.

p-benzynes have been reviewed recently and the interested reader is refered to the cited literature for further information.1,59

Detailed thermochemical data for the Bergman rearrangement were determined by Roth et al.60 from gas-phase NO trapping experiments. The activation barrier for ring opening of 28 to enediyne (Z)-16 was reported as 19.8 kcal/mol, the enthalpy of formation of (Z)-16 ( H f,298 ¼ 129.5 kcal/mol) is lower than that of p-benzyne ( H f,298 ¼ 138 1 kcal/mol) by 8.5 kcal/mol. The too low values for the enthalpy of formation of 28 determined in an earlier work by Squires and co-workers23a using collision induced dissociation (CID) measurements was corrected to 137.8 2.9 kcal/mol in a later reinvestigation, now in perfect agreement with Roth’s data.22 Problems are encountered with an exact quantum chemical treatment of biradicals (and in particular their reactions), which requires a balanced treatment of dynamic and nondynamic (near-degeneracy) contributions to the correlation energy. On the other hand, precise experimental data are available for p-benzyne and the Bergman cyclization. Thus, this reaction has become a testing ground for ab initio and DFT methods.61 Still, there is no general agreement about the performance and suitability of different quantum mechanical approximations, especially with regard to density functional theory.

In certain cases, the Bergman cyclization can be triggered photochemically, although the number of examples described in the literature is limited.62 Recently, the electronic details of the photochemical enediyne cycloaromatization were investigated computationally.63 The low-lying excited states of enediyne (16) can be described as a linear combination of the configurations of weakly interacting ethylene and acetylene units. According to this model, excitation of the ethylene fragment induces cis–trans isomerizations and hydrogen abstractions in addition to Bergman cyclization, and the photochemical cycloaromatization is most likely initiated by excitation of the acetylene unit. Moreover, the cyclization is more likely to occur on the 21A potential energy surface than from the 13B state. Although the reaction is more exothermic in the latter case ( 42 kcal/mol compared to 18 kcal/ mol at the CASMP2 level), the probability of cis–trans isomerization and hydrogenabstraction is increased concurrently.63 Consistently, Hopf et al.64 observed photochemical cis–trans isomerization of 16 in the presence of a triplet sensitizer (Michler’s ketone). Note, however, that systematic investigations of factors (substituents or sensitizers) facilitating the photochemical ring closure or inhibiting competing reaction pathways, have not been carried out yet, although this reaction is of potential interest for tumor therapy.

The first direct observation of a derivative of p-benzyne was reported by Chapman et al.65 in 1976. Irradiation of anthraquinone bisketene (32) in organic glasses at 77 K produced a new species with UV absorptions in the range from 256 to 449 nm. After subsequent warming to room temperature, anthracene was isolated from the solution. An analogous experiment in the presence of 5% CCl4 yielded 9,10-dichloroanthracene. In an argon matrix at 10 K, two IR absorptions at 710 and 760 cm 1 were observed for the new species. Based on the trapping reactions and the absence of an electron spin resonance (ESR) signal, the photolysis product was identified as 9,10-didehydroanthracene 1A1-33 (Scheme 16.13).65 In

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O

Scheme 16.13. 9,10-Didehydroanthracene (33) was generated from various precursors, but rapidly rearranges to cyclic diyne 35.

1996, Chen and co-workers investigated the photochemistry of dehydrodianthracene (34) using laser flash photolysis (LFP) and were able to identify two transients: a short lived species with a lifetime of 2.1 ms and an absorption maximum at 295 nm, and a long-lived species (500 ms) with an absorption at 335 nm. The shortlived transient was assigned to 9,10-didehydroanthracene (33), the long-lived photolysis product was identified as 3,4-benzocyclododeca-3,7,9-triene-1,5-diyne (35).66a Since the UV spectroscopic data of 33 from the LFP study were in disaccord with Chapman’s early study, Sander and co-workers67 reinvestigated the photochemistry of bisketene (32) in argon matrices. By using alternative precursors and by comparison with DFT calculated IR spectra, it could be demonstrated that 9,10-didehydroanthracene (33) is labile even under matrix isolation conditions, and that the IR absorptions observed by Chapman et al.65 belong to cyclic diyne 35. Pyrolysis of various precursors produced only 35 as well (Scheme 16.13).67,68 According to the DFT calculations and LFP measurements, the barrier for ring opening of 33 was estimated to be 10–12 kcal/mol, and diyne 35 is 6–8 kcal/ mol more stable than didehydroanthracene (33).67,68