Tautomerization adducts

Cinnoline-2-imine 436 with DMAD yields a mixture of the tautomeric adducts 438 and 439.426 They are clearly formed by initial cycliza-tion onto the 1-nitrogen atom (437), followed by ring scission as shown. The alternative mode of cyclization, onto carbon, although favored in the pyridazine series, is not possible here unless the resonance of both rings is disrupted. 

We conclude the proton transfer to be much faster than the rotation of the adduct, so that it cannot be affected by the high field. The reaction partners of the field-sensitive, one-step equilibrium are the hardly polar acid and base on the one hand, and the polar rapidly tautomerizing adduct on the other hand. With unequal amounts of acid and base the mechanism becomes more involved. 

The mean chemical shifts of A- unsubstituted pyrazoles have been used to determine the tautomeric equilibrium constant, but the method often leads to erroneous conclusions (76AHC(Sl)l) unless the equilibrium has been slowed down sufficiently to observe the signals of individual tautomers (Section 4.04.1.5.1). When acetone is used as solvent it is necessary to bear in mind the possibility (depending on the acidity of the pyrazole and the temperature) of observing the signals of the 1 1 adduct (55) whose formation is thermodynamically favoured by lowering the solution temperature (79MI40407). A similar phenomenon is observed when SO2 is used as solvent. 

The addition of benzonitrile oxide to cyclooctatetraene produced a monoadduct which was induced to undergo valence tautomerism to produce a tricycloisoxazoline (Scheme 104). A similar reaction with tropone gave a minimum of eight adducts from which two monoadducts were isolated (Scheme 104) (70T5113). 

Even the earliest reports discuss the use of components such as polymer syrups bearing carboxylic acid functionality as a minor component to improve adhesion [21]. Later, methacrylic acid was specifically added to adhesive compositions to increase the rate of cure [22]. Maleic acid (or dibasic acids capable of cyclic tautomerism) have also been reported to increase both cure rate and bond strength [23]. Maleic acid has also been reported to improve adhesion to polymeric substrates such as Nylon and epoxies [24]. Adducts of 2-hydroxyethyl methacrylate and various anhydrides (such as phthalic) have also been reported as acid-bearing monomers [25]. Organic acids have a specific role in the cure of some blocked organoboranes, as will be discussed later. 

Mechanism The reaction of and A -steroids with nitrosyl fluoride to form ni trimines is best discussed in conjunction with the nitrosyl chloride reaction leading tothe5a-chloro-6 -nitro steroids (33). Since nitroso alkanes are oxidized with nitrosyl chloride to nitro alkanes it is believed that 5a-chloro-6j5-nitro steroids are formed in this way from an initially formed 5a-chloro-6 -nitroso adduct. The same is true for nitrosyl fluoride up to the stage of the nitroso fluoride (56). Since NOF is a weaker oxidizing agent than NOCl the nitroso fluoride tautomerizes to the fluoro oxime (57) at a rate... 

Benz[/]isoindole 10 exists, on the basis of spectroscopic examination, predominantly in the benzenoid tautomeric form 10b, although the formation of the Diels-Alder adduct with N-phenylmaleimide suggests the presence of a small amount of the o-quinoid tautomer 10a (78JOC4469). 

An interesting example of the N(9)-C(8) prototropic tautomerism has been reported for the caffeine radical by pulse radiolysis studies in aqueous solution the transformation of the heteroatom-protonated electron adduct 25 into the carbon-protonated tautomer 26 occurred spontaneously in neutral media [95JCS(F)615]. 

Another pathway for the aromatization of the cr -adducts was found in the reactions of 3-pyrrolidino-l,2,4-triazine 4-oxide 81 with amines. Thus the treatment of 1,2,4-triazine 4-oxide 81 with ammonia leads to 5-amino-1,2,4-triazine 4-oxides 54—products of the telesubstitution reaction. In this case the cr -adduct 82 formed by the addition of ammonia at position 5 of the heterocycle undergoes a [l,5]sigmatropic shift resulting in 3,4-dihydro-1,2,4-triazine 83, which loses a molecule of pyrrolidine to yield the product 54. This mechanism was supported by the isolation of the key intermediates for the first time in such reactions—the products of the sigmatropic shift in the open-chain tautomeric form of tiiazahexa-triene 84. The structure of the latter was established by NMR spectroscopy and X-ray analysis. In spite of its open-chain character, 84 can be easily aromatized by refluxing in ethanol to form the same product 54 (99TL6099). 

Open-chain tautomerism is a general feature of 4-hydroxy-3,4-dihydro-1,2,4-triazines, including cr -adducts at position 3 of the 1,2,4-triazine 4-oxides. Thus triazahexatrienes 85 are the open-chain form of cr -adducts 86 and can be aromatized by oxidation with KMn04, yielding 3-amino-1,2,4-tiiazine 4-oxides 88 (98ZOR418). 

Van der Plas et al. (86JOC1147) demonstrated that the formation of identical tautomeric 1,2-dihydropyrimidines 46a and 46a on amination of 5-nitropyrimidine is favored at a low temperature, while ammonia addition at room temperature produces the thermodynamically more stable 1,4-dihydro adduct 46b (Scheme 15). 

The different ratios of 52/53 produced by cycloadditions performed at atmospheric and high pressure, and the forma tion of the unusual trans adducts 53, have been explained by the facts that (i) Diels-Alder reactions under atmospheric pressure are thermodynamically controlled, and (ii) the anti-endo adducts 52 are converted into the short-lived syn-endo adducts 54 which tautomerize (via a dienol or its aluminum complexes) to 53. The formation of trans compounds 53 by induced post-cycloaddition isomerization makes the method more flexible and therefore more useful in organic synthesis. 

Numbers used in this cycle AG° for hydroxide plus monomethyl sulfate, assumed to be the same as for dimethyl sulfate estimated above AG° for ionization of monomethyl sulfate AG° for tautomerization of the anionic adduct, based on pK values estimated by the method of Branch and Calvin AG° for ionization of the apically protonated adduct, based on a pK estimated by the method of Branch and Calvin.)... 

Quantum calculations on metal-assisted tautomerization indicate a substantial stabilization to protonation of the endocyclic nitrogen atoms (99). In the case of HgCHg, adducts are formed by binding at either A-N6 or C-N4, which increases the stability of the respective N1H+ or N3H+ protonated species by 10-14 kcal/mol. For Pt11 binding at C-N4 the effect is much greater at 30-34 kcal/mol. 

As described previously, the two-component coupling reaction between amidox-ime 50 and DM AD generated a mixture of Z- and E-adducts 51, which was heated in xylenes to afford hydroxypyrimidinone 55 (Scheme 6.20). The previously proposed mechanism involved tautomerization of 51 to 52, followed by a Claisen [3,3]-rearrangement to yield intermediate 53. Subsequent tautomerization of the intermediate 53 to 54, followed by cyclization would afford 55 [9a,f]. 

Later it was shown in reactions of aromatic aldehyde methylhydrazones 137a-f with benzonitrile oxide that the initially formed Z-adduct 138, depending on the reaction procedure and the substituents, undergoes either isomerization to the thermodynamically stable E-adduct 139, tautomerization to an oxatriazine 140 or irreversible cyclization to a triazole 141 (Scheme 1.28). The structure of 4-methyl-3.6-diphenyl-5,6-dihydro-4//-1,2.4,5-oxatriazinesl40a was confirmed by an X-ray study (308). 

With an electrophilic transition metal complex, it is believed that the hydration of an alkyne occurs through a trans-addition of water to an 72-alkyne metal complex (Scheme 15, path A),380 although the m-pathway via hydroxymetallation has also been proposed (path B).381,382 However, distinguishing between the two pathways is difficult due to the rapid keto-enol tautomerization that renders isolation of the initial water adduct challenging. 

Pulsed radiolysis in NO-saturated aqueous solution at a variety of wavelengths has been used to generate hydroxyl radicals and measure the rate of addition to 1,4-benzoquinones. Mechanistically, the kinetic data indicated that the first-formed adduct undergoes a rapid keto-enol tautomerism to give (56). ... 

In contrast to Nair, Bode and co-workers propose that cross-benzoin adduct LVII is formed which then undergoes an oxy-Cope rearrangement to form LVIII (Scheme 38). Tautomerization and indamolecular aldol reaction occurs following the catalytic cycle proposed by Nair. 

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