Pyridines, Dewar isomers

A Dewar isomer of unsubstituted pyridine was identified by Wilzbach, but it was very unstable.63 Other Dewar isomers of six-membered heterocycles, isolated and fairly stable, are substituted with perfluoroalkyl groups. However, 1,2-dihydroheterocyclic compounds such as a-pyrone or a-pyridone derivatives are easily photoisomerized to bicyclic Dewar isomers, which are useful for the synthesis of cyclobutadienes. The photochemistry of 1,2-dihydroheterocyclic compounds will be discussed, followed by those of fully aromatic compounds. 

The two examples just considered seem to suggest that the photoreaction of perfluoroalkylated pyridines would give the 1,4-bonded Dewar isomers. However, the photoreaction of 2,6-bis(heptafluoroisopropyl)-3,5-bis(penta-fluoroethyl)-4-trifluoromethylpyridine gave a product whose structure... 

Dihydropyridine is fairly unstable and susceptible to oxididation but the Dewar isomer prepared from it by photolysis is rather stable and used as masked 1,2-dihydro-pyridine (i35) 144). 

In 1977, the 2,5-bonded Dewar isomers of perfluoroalkylated pyridine were isolated by Chamber s group (145) 156). The photolysis was carried out in the gas phase. Therefore, thse isomers must be the primary products. Their distributions seems to be determined by the electronic interaction between the substituents on the double bonds and steric effects. 

A pentafluoro-Dewar-pyridine, tentatively assigned the structure (5), has been isolated in very low yield from the complex mixture obtained in about 400 photolyses of pentafluoropyridine its half-life is about 5 days at room temperature. Flash photolysis studies of pentafluoropyridine provide evidence for two aza-fulvene isomers (6) and (7), and it is suggested that an aza-benzvalene is the precursor to both the fulvenes and the Dewar isomer, although this mechanistic argument is quite speculative. The first hetero-benzvalene to be isolated and... 

The Dewar isomer, 123, of 3-methyl-4(3H)-pyrimidinone (122) was generated in argon matrices by 308 nm irradiation of the parent molecule and identified by comparison of the experimental matrix IR spectrum with spectra computed for 123 and other possible products. " For several 4(3H)-pyrimidinones not methylated at N3, two other types of matrix photoreactions were observed in addition to the isomerization to the Dewar isomer phototautomerism and ring opening. Somewhat later, matrix isolated Dewar pyridine (124) was produced by UV-irradiation of pyridine in solid argon and was identified with the aid of DFT computations. On further photolysis, 124 produced cyclobutadiene (118) and HCN. 

When pyridine derivatives 147, 148, and 149 (Scheme 45) were irradiated at 254 nm using a slow transference technique, however, the 2,5-bonded Dewar-pyridines were the major or only valence isomers formed. AH of these Dewar-pyridine isomers rearrange at 160°C to the corresponding pyridine. Preference for 2,5-bonding was also observed in the photoisomerizations of tri-t-butylpyridines 155,156, and 157 to the Dewar-pyridine 158,159, and 160 shown in Scheme 46. As expected, preference is for the 2,5-bonded Dewar isomers, in which steric interference of the three adjacent t-butyl groups is minimized. 

The steric and dipole-dipole effects of the CF3 group on valence isomerization in the Dewar pyridine-azaprismane-pyridine system have been studied. These reveal themselves in the high stability, compared to the pyridine, of the valence isomer arising out of the large activation energy for rearomatization. The transformation of a 1-Dewar to 2-Dewar pyridine was observed (89T3115). 

Kinetic studies on the quaternization reaction of pentamethylpyridine (154A, Scheme 64) and its deuterated congener suggest that there may be an equilibium between this aromatic pyridine and its valence isomer, pentamethyl-Dewar-pyridine (154B). It is known that such valence isomers are stabilized by steric factors such as encountered in pentamethylpyridine.194195 On determining conductometrically the initial rate of quaternization with methyl iodide for polymethylpyridines in acetone, it was found that all but one followed clean bimolecular kinetics. Pen-... 

Proof for the existence of benzene isomers in irradiated benzene has been obtained in several ways. These will not be discussed in detail, but they may be classified broadly as physical and chemical. Nuclear magnetic resonance has been used by Wilzbach and Kaplan to identify benzvalene.39 Prismane has also been identified by NMR and by vapor-phase chromatography. The Dewar form has been synthesized in several steps which start with ris-1,2-dihydrophthalic anhydride. Photochemically this compound yields bicyclo(2,2,0)hexa-5-ene-2,3-dicarboxylic aqid anhydride. This was followed by catalytic reduction and oxidative decarboxylation to give the Dewar form of benzene.39 The method of synthesis alone provides some basis for structure assignment but several other bits of supporting evidence were also adduced. Dewar benzene has a half-life of about 48 hr at room temperature in pyridine solution and its stability decreases rapidly as the temperature is raised. 

These examples show that the 2,5-bonded Dewar pyridine can be formed even if it is substituted with perfluoroalkyl groups. In the second example in Scheme 38 another 2,5-bonded isomer was not formed. This fact shows that a steric effect is important. 

The photolysis of substituted pyridines causes migration of the substituent, and a mechanism involving intermediate formation of a Dewar-type isomer and an aza-prismane has been proposed 148). However, the formation of these intermediates has not been confirmed so far (139). 

This result is in accordance with MO calculations according to which a 2,5-bonded Dewar pyridine is expected to be more stable than the 1,4-bonded isomer... 

The above two Dewar pyridines bear the same substituents in the 2-, 4-, and 6-position. Therefore, isomerization between these positions could not be observed. Chambers and his coworkers examined the photoreaction of a perfluoropyridine bearing three kinds of substituents and suggested that first a 2,5-bonded Dewar pyridine is formed which is subsequently isomerized to the 1,4-bonded Dewar compound although the 2,5-bonded isomer has not been observed (144)155>. 

Photolysis of highly substituted pyridines gives rise to isolable and stable valence isomers. For instance, pentakis(pentafluoroethyl)pyridine 101 is converted almost quantitatively into the symmetrical 1-aza-DEWAR pyridine 102. Further irradiation brings about its rearrangement to the corresponding azaprismane derivative 104 [59] ... 

In contrast to 101, photolysis of the highly substituted pyridine 105 leads to the formation of both possible Dewar pyridines 106 and 107 with excess of the 2-aza isomer ... 

CMe CF CF-CFs + EtaN-CiCMe-CFa-CF-CFs ss] can be found in Chapter 2 (pp. 62,72) and production of the Dewar valence-isomer of pentakis(pentafluoro-ethyl)pyridine (53) is also discussed elsewhere (p. 93). An interesting synthesis of the fluoroenamine (54 X = CF CF2) has emerged from studies on aza[I3]-... 

The Dewar and prismane isomers of perfluoropentaethylpyridine have been isolated (see p. 93). The Dewar pyridine (299) is formed photochemically from its aromatic isomer (299) forms stable complexes with palladium(ii). Tris(trifluoro-methyl)-sym-triazine, upon photolysis in hydrocarbon solution, does not undergo isomerization but yields mixtures of dihydro-compounds, adducts with the solvent, and substituted compounds. The Dewar ophen (300) (Vol. 2, p. 443)... 

Polyperfluoroalkyl substitution greatly stabilizes both Dewar-pyridine and azaprismane valence isomers. Irradiation of pentakis(pentafluoroethyl)pyridme 134 in perfluoro-n-pentane with Hght of A, >... 

It is interesting to note that these conversions indicate a strong preference for formation of the 1,4-bonded Dewar-pyridine isomer despite the prediction that the 2,5-isomer is the more stable isomer. The conversion of pyridine 145 (Scheme 44) to the 1,4-bonded Dewar-pyridine 146 is another example of this preference. ... 

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