Tautomers, valence

The 2,1-benzisoxazolium salts unsubstituted in the 3-position behave in an analogous manner to their 1,2-isomers above. Particularly interesting is the reaction of the salt (134) with EtaN. Abstraction of the C(3)-proton is followed by ring opening to the iminoketene (135) which undergoes electrocyclization to its stable valence tautomer (136) in 84% yield (71JA1543). 

Apparent nucleophilic attack on large, fully unsaturated rings may occur by way of attack on a valence tautomer, such as the reaction of oxepin with azide ion. Attack on the oxanorcaradiene valence tautomer leads to ring opening of the three-membered ring, and formation of 5-azido-6-hydroxy-l,3-cyclohexadiene (Section 5.17.2.2.4). 

Concerted cycloadditions are observed with heterocyclics of all ring sizes. The heterocycles can react directly, or via a valence tautomer, and they can utilize all or just a part of unsaturated moieties in their rings. With three-membered rings, ylides are common reactive valence tautomers. Open chain 47T-systems are observed as intermediates with four-membered rings, and bicyclic valence tautomers are commonly reactive species in additions by large rings. Very often these reactive valence tautomers are formed under orbital symmetry control, both by thermal and by photochemical routes. 

The interaction of diazomethane with 1-azirines was the first example of a 1,3-dipolar cycloaddition with this ring system (64JOC3049, 68JOC4316). 1,3-Dipolar addition produces the triazoline adduct (87). This material can exist in equilibrium with its valence tautomer (88), and allylic azides (89) and (90) can be produced from these triazolines by ring cleavage. 

Reaction of the azocine (212 R = Me) with DMAD yields the fused 1-azetine (213) by Diels-Alder cycloaddition to the bicyclic valence tautomer (211 R = Me) (71JOC435, 71JA152). 

The formation of transient benzazetidinones (251) in the photolysis and thermolysis of benzotriazin-4-ones (250) is well established (76AHC215) and the highly hindered adamantyl derivative has actually been isolated from flash pyrolysis of 4-adamantylbenzotriazinone (73JCS(Pl)868). A second route to such hindered benzazetidinones involves cyclization of the iminoketene valence tautomer (252 R = Bu ), the latter being generated by deprotonation of the anthranilium salts (253) (71JA1543). 

The thermal rearrangements of methyl-substituted cycloheptatrienes have been proposed to proceed by sigmatropic migration of the norcaradiene valence tautomer. The first step is an electrocyclization analogous to those discussed in Section 11.1. 

Strained pertrifluoromethyl-substituted valence tautomers of aromatic systems, such as tetrakis(trifiuoromethyl)Dewar thiophene [87] and hexalas(tnfluorQ-methyl)benzvalene [Diels-Alder reactions with various cyclic and acyclic dienes (equations 76 and 77). 

Treatment of dimethyl sulfoxide (DMSO) is reported to lead to 2-phenylisoindole (17) in yields up to 40%. An interesting possibility in this case is involvement of the isoindole valence tautomer (67) as an intermediate. P. A. Barrelt, R. P. LinsteacI, G. A. P. Tuey, and J. M. Robertson, J. Chem. Soc. p. 1809 (1939). 

Three decades ago the preparation of oxepin represented a considerable synthetic challenge. The theoretical impetus for these efforts was the consideration that oxepin can be regarded as an analog of cyclooctatetraene in the same sense that furan is an analog of benzene. The possibility of such an electronic relationship was supported by molecular orbital calculations suggesting that oxepin might possess a certain amount of aromatic character, despite the fact that it appears to violate the [4n + 2] requirement for aromaticity. By analogy with the closely related cycloheptatriene/norcaradiene system, it was also postulated that oxepin represents a valence tautomer of benzene oxide. Other isomers of oxepin are 7-oxanorbornadiene and 3-oxaquadricyclane.1 Both have been shown to isomerize to oxepin and benzene oxide, respectively (see Section 1.1.2.1.). 

Thermolysis (115°C) or irradiation of the epoxide 3, generated from bicyclo[2.2.0]hexa-2,5-diene ( Dewar benzene") with 3-chloroperoxybenzoic acid, gives a mixture of the valence tautomers oxcpin and benzene oxide together with traces of phenol.111112... 

Treatment of methyl 6-phenyl-l,2,4-triazine-3-carboxylate (41) with cyclopropene produces methyl 6-phenyl-4//-azepine-2-carboxylate (42) in equilibrium with its bicyclic valence tautomer 43, which undergoes a second cycloaddition with cyclopropene to yield the bisadduct 44.112... 

In some instances, the azaquadricyclane is nonisolable and photolysis of the pyrrole-dimethyl acetylenedicarboxylate cycloadduct or of analogous cycloadducts gives directly the 1 //-azepine. For example, 3.6-dichloro-l-tosyl-l//-azepine (10) is produced in excellent yield by photolysis of the [4 + 2] cycloadduct 9.22 Interestingly, dichloroazepine 10 is found (by H NMR spectroscopy) to be in equilibrium with a small amount (1 % at — 67 C) of its bicyclic valence tautomer 11. 

From detailed HNMR spectroscopic analyses of 4//-azepine systems it has been concluded that 4//-azepines are energetically more favorable than their bicyclic 3-azabieyclo[4.1.0]hepLa-2,4-diene valence tautomers 85 however, the valence tautomer 10 of methyl 6-phenyl-4//-azepine-2-carboxylate (9) has been trapped as the [4 + 2] cycloadduct 11 with 3,3-dimethyl-cyclopropene.112... 

A reactivity index which accurately predicts the site selectivity of the photoisomerization of cycloheptatrienes to their bicyclic valence tautomers fails with 1//-azepines.237 For example, for methyl 2-methyl-1//-azepine-l-carboxyIatc (14), the 1-methyl isomer 16 is the predicted major product in practice the reverse is true. 

Irradiation of dimethyl ,2.7-trimethyl-l//-azcpinc-3,6-dicarboxylate (5) yields methyl 1,2,5-trimethylpyrrole-3-carboxylate (7) most probably by loss of methyl propiolate from the bicyclic valence tautomer 6 (cf. Houben-Weyl, Vol.6a, p719).239... 

Diazomethane and 1 -substituted 1 //-azepine-4,5-dicarboxylates 44 yield the C4 — C5 pyrazoline adducts, e. g. 45.234 In contrast, the 1-mesyl and the 1-tosyl derivatives yield only adducts of the benzene imine valence tautomers of the l//-azepines. 

The first reported derivative of 1,2-oxazepine was dibenz[f,/][l,2]oxazepine-ll-carbonitrile (3 a). This, together with small amounts of compounds 4 and 5, is formed when acridine-9-carbonitrile 10-oxide (la) is irradiated with UV light,6,7 It is likely that the reaction proceeds by way of the oxaziridine valence tautomer 2a, which, however, was not detected.7 Photo-isomcrization of 9-chloroacridine 10-oxide (lb) yields the 11-chlorodibenzoxazepine 3b.6,7... 

The thienodiazepine 1 is converted into the diazetothienopyrrole 2 by irradiation the isomer 3 similarly gives the valence tautomer 4.142... 

Heating the acetyltriazepine 2 in 1,2-dichlorobenzene in a sealed tube at 190-200CC for 65 hours gives yV-acetyl-5,6-dimethoxypyrazin-2-amine (4) presumably via the bicyclic valence tautomer 3.371... 

Unsymmetrically substituted formazans form a complex mixture of valence tautomers and geometric isomers with different conformations. The tautomerism is further complicated when substituents on the aryl ring are... 

When isolated, this highly strained valence tautomer of benzene exploded violently when scratched. It may be handled safely in solution in ether. 

The next debate in the literature was whether these molecules have C2v or Cs symmetry. The nuclear motion of a C2v symmetric structure would be described by a single-well potential (see Figure 10). The alternative is a rapid interconversion of two valence tautomers, each of Cs symmetry. This would occur via the C2v structure as transition state (see Figure 11). In this case the motion of the central sulfur would be described by a double-well potential, and dioxathiapentalene and trithiapentalene would be misnomers for (3//-l,2-oxathiol-3-ylidene)acetaldehyde 180 and (3/7-1,2-dithiol-3-ylidene)thioacetaldehyde 181. One advantage of C2v symmetry is aromatic stabilization from the 1071 electrons <2001CRV1247>. The alternative Cs symmetry has the advantage of avoiding a hypervalent sulfur. 

Perrin et al. probed the structures of 174 and 175 by using the 13C NMR method of isotopic perturbation of equilibrium <2001PCA11383>. The goal of this study was to measure the 13C NMR chemical-shift difference between C5 of a-deuterated molecule and C2-(5) of undeuterated molecule (see Equation 48). If 174 or 175 is a mixture of valence tautomers 180-r/ia and 180-r/]b or 181-equilibrium isotope shift (Aeq) will be observed in addition to the intrinsic isotope shift (5A0). In contrast, if 174 or 175 has C2v symmetry, then only (5A0) will contribute. 

Cyclopropenone formation should involve the bisketene 46 and its decarbonylation to the monoketene 47 (a valence tautomer of cyclopropenone 44), since photolysis in protic media like ethanol produces diethoxy diethyl tartrate 45) (meso and d,l). This method was also successful in the case of l,2-diphenyl-3,3-dichloro-cyclo-butene dione (48) giving rise to diphenyl cyclopropenone49 (but as for 44 only a moderate yield was produced) ... 

Azirines254 in principle react analogously to Schiff bases the 2,3-diphenyl pyridones-4 403 obtained from diphenyl cyclopropenone may well result from a primary betaine 401, which reorganizes to the pyridone-4-system via its valence tautomer, the ketene 402. 

Electrocyclic reactions have been performed with three of the bridged [ 11 Jan-nulenones. Both 11 and 13, which both contain a cycloheptatriene unit, undergo Diels-Alder additions with dienophiles via their norcaradiene valence tautomers 41 and 43 and yield adducts of the type 42 and 44. Annulenone 13 was found to react only with 4-phenyl-l,2,4-triazoline-3,5-dione whilst 11 underwent reaction with a variety of dienophiles. 3,8-Methano[ 11 Jannulenone 12 contains a tetraene system and undergoes addition reactions, apparently of the (8 + 2)-type, at the termini of the tetraene system. Thus with maleic anhydride the adduct 46, the valence tautomer of the initial adduct 45, was isolated. 

AP108) from the reaction of hydrazine with sodium nitrite in acetic acid. Treatment of 625 (R = Et) with sodium nitrite in acetic acid gave 656 (R = Et) through the 3-azido valence tautomer 654 (R = Et) (87API 191). 

This linear polysulflde obviously formed according to the sequence 2,5-di(thiocyano) thiophene potassium 2-mercaptido-5-thiacyanonothiophene —> (tristhio)maleic anhydride thiophene-2,5-disulfenyl biradical (the diradical valence tautomer) —> the depicted linear polymer in which the thiophene rings are connected through disulfide bridges (Scheme 8.17). 

Thiazete (156) heated with elemental sulfur gives 1,2,4-dithiazoline (158) via its ring opened valence tautomer (157) (Scheme 34) <86CZ87>. 

The meso-ionic 1,3-oxazol-S-ones show an incredible array of cycloaddition reactions. Reference has already been made to the cycloaddition reactions of the derivative 50, which are interpreted as involving cycloaddition to the valence tautomer 51. In addition, an extremely comprehensive study of the 1,3-dipolar cycloaddition reactions of meso-ionic l,3-oxazol-5-ones (66) has been undertaken by Huisgen and his co-workers. The 1,3-dipolarophiles that have been examined include alkenes, alkynes, aldehydes, a-keto esters, a-diketones, thiobenzophenone, thiono esters, carbon oxysulfide, carbon disulfide, nitriles, nitro-, nitroso-, and azo-compounds, and cyclopropane and cyclobutene derivatives. In these reactions the l,3-oxazol-5-ones (66)... 

Photolysis (2537 A) in methyl cyanide solution of the compound 243, R = Me, = Ph, gives iV-methylthiobenzamide. This reaction has been interpreted in terms of the homolysis of the valence tautomer 244, which has been detected spectroscopically ( % 2260 cm N=C=0). The l,3,4-thiadiazol-2-ones have dipole moments (243, R = R = Ph,/U = 7.75 D 243, R = Me, R = Ph, /U = 7.7 D) consistent with their meso-ionic formulation. They react with triethyloxonium tetra-fluoroborate, yielding the salts 245. The compound 243, R = Me, R = Ph, and aniline gives the semicarbazide 246. ... 

---