Methyl-methylene tautomerism

In CHEC(1984) 1984CHEC(2)1 and CHEC-II(1996) 1996CHEC-II(6)1 , examples of keto-enol, thione-thiol, amino-imino, methyl-methylene tautomerism were given. New examples of most of these subclasses appeared since 1995. 

On the basis of H NMR, nuclear Overhauser effect (NOE) experiments, and X-ray diffraction Guard and Steel showed that earlier reported benzylidene-4,5-dihydropyridazines should be represented as aromatic pyridazine 

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Occurrence of the methyl-methylene tautomerism in azoles needs a strong electron-withdrawing substituent attached to the methyl group. 

Finally, we note that Karelson et al. [295] have used the D02 model with small cavity radii to consider aqueous solvation effects on other tautomeric equilibria of substituted pyridines. In particular, they examined methyllmethylene, amino/imino, hydroxy/oxo, and mercapto/thiono substitution at the 2-, 3, and 4-positions of pyridine. They observed methyl/methylene equilibria to be only slightly perturbed by aqueous solvation. Amino/imino equilibria were slightly more perturbed, followed by hydroxy/oxo equilibria. Mercapto/thiono equilibria were very significantly affected by aqueous solvation Karelson et al. predicted pK shifts of up to 16 units. This sensitivity of the thiono group to solvation is also discussed in the next section. Overall, the tautomeric equilibria of 3- and 4-substituted pyridines were more sensitive to aqueous solvation than were those of 2-substituted pyridines. 

Benzothiazoline, N-methyl-2-methylene-structure, 6, 238 Benzothiazolines aromatization, 6, 270 oxidation, 6, 272 structure, 6, 238 synthesis, 6, 323, 325 Benzothiazoline-2-thione, 3-methyl-in organic synthesis, 6, 329 Benzothiazoline-2(3 f/)-thiones tautomerism, 6, 248 Benzothiazolin-2-one alkylation, 6, 286 Benzothiazolin-2-one, 3-methyl-hydrazone... 

Furan, 2,3-dihydro-5-methyl-polymers, 1, 276 Furan, 2,3-dihydro-3-methylene- H NMR, 4, 577 Furan, 2,5-dihydro-2-methylene- H NMR, 4, 577 tautomerism aromaticity and, 4, 595 Furan, 2,5-dihydro-2-nitro-structure, 4, 550 Furan, 2,3-dihydroxy-tautomerism, 4, 37 Furan, 2,4-dihydroxy-tautomerism, 4, 37 Furan, 3,4-dihydroxy-tautomerism, 4, 37 Furan, 2,5-diiodo-nitration, 4, 602 synthesis, 4, 712 Furan, 3,4-diiodo-reactions, 4, 650 Furan, 2,3-dimethoxy-synthesis, 4, 625, 648 Furan, 2,5-dimethoxy-synthesis, 4, 648 Furan, 3,4-dimethoxy-cycloaddition reactions, 4, 64, 625 lithiation, 4, 651 reactions... 

Hydantoin, 5,5-diaryl-2,4-dithio-methylation, 5, 444 Hydantoin, 1,3-divinyl-polymers, 1, 280 Hydantoin, 5-methylene-polymers, 1, 280 Hydantoin, 5-phenyl-2-thio-tautomerism, 5, 370 Hydantoin, thio-... 

Oxazol-5(2H)-one, 2-benzylidene-4-methyl-tautomerism, 6, 186 Oxazol-5(2ff)-one, 2-methylene-isomerization, 6, 226 Oxazol-5(2H)-one, 2-trifluoromethyl-acylation, 6, 201 Oxazol-5(4ff)-one, 4-allyl-thermal rearrangements, 6, 199 Oxazol-5(4H)-one, 4(arylmethylene)-Friedel-Crafts reactions, 6, 205 geometrical isomerism, 6, 185 Oxazol-5(4ff)-one, 4-benzylidene-2-phenyl-configuration, 6, 185 photorearrangement, 6, 201 Oxazol-5(4ff)-one, 4-benzyl-2-methyl-Friedel-Crafts reactions, 6, 205 Oxazol-5(4ff)-one, 4-methylene-in amino acid synthesis, 6, 203 Oxazol-5(4ff) -one. 2-trifluoromethyl-hydrolysis, 6, 206 Oxazolones... 

The salts of some enamines crystallize as hydrates. In such cases it is possible that they are derived from either the tautomeric carbinolamine or the amino ketone forms. Amino ketone salts (93) ( = 5, 11) can serve as examples. The proton resonance spectra of 93 show that these salts exist in the open-chain forms in trifluoroacetic acid solution, rather than in the ring-closed forms (94, n = 5, 11). The spectrum of the 6-methylamino-l-phenylhexanone cation shows a multiplet at about 2.15 ppm for phenyl, a triplet for the N-methyl centered at 7.0 ppm and overlapped by signals for the methylene protons at about 8.2 ppm. The spectrum of 93 ( = 11) was similar. These assignments were confirmed by determination of the spectrum in deuterium oxide. Here the N-methyl group of 93 showed a sharp singlet at about 7.4 ppm since the splitting in —NDjMe was much reduced from that of the undeuterated compound. 

Heterocyclic enamines A -pyrroline and A -piperideine are the precursors of compounds containing the pyrrolidine or piperidine rings in the molecule. Such compounds and their N-methylated analogs are believed to originate from arginine and lysine (291) by metabolic conversion. Under cellular conditions the proper reaction with an active methylene compound proceeds via an aldehyde ammonia, which is in equilibrium with other possible tautomeric forms. It is necessary to admit the involvement of the corresponding a-ketoacid (12,292) instead of an enamine. The a-ketoacid constitutes an intermediate state in the degradation of an amino acid to an aldehyde. a-Ketoacids or suitably substituted aromatic compounds may function as components in active methylene reactions (Scheme 17). 

Reactions of potentially tautomeric methyl and methylene derivatives of pyridine with N-electrophiles 98KGS147. 

Quinoxalin-2-ones are in tautomeric equilibrium with 2-hydroxy-quinoxalines, but physical measurements indicate that both in solution and in the solid state they exist as cyclic amides rather than as hydroxy compounds. Thus quinoxalin-2-one and its A -methyl derivative show practically identical ultraviolet absorption and are bases of similar strength. In contrast, the ultraviolet spectra of quinoxalin-2-one and its 0-methyl derivative (2-methoxyquinoxaIine) are dissimilar. The methoxy compound is also a significantly stronger base (Table II). Similar relationships also exist between the ultraviolet absorption and ionization properties of 3-methylquinoxalin-2-one and its N- and 0-methyl derivatives. The infrared spectrum of 3- (p-methoxy-benzyl)quinoxalin-2-one (77) in methylene chloride shows bands at 3375 and 1565 cm" which are absent in the spectrum of the deuterated... 

Methyl-4-phenyl-l,2,5-thiadiazole 1,1-dioxide 21 suffers proton abstraction in basic nonaqueous media to give a resonance stabilized anion 43, neutralization of which using anhydrous TFA gives the orange tautomer 4-methylene-3-phenyl-l,2,5-thiadiazoline 1,1-dioxide 44 (Scheme 3) <2001JP0217>. The tautomeric equilibrium is practically displaced toward 21 in acetonitrile and toward 44 in DMF. 

Methylbenzofuran-3-carbaldehydes undergo ready condensation with Meldrum s acid (isopropylidene malonate) to afford arylmethylene derivatives 83. These on flash vacuum pyrolysis at 500-600 C give 3-dibenzofuranols 84 (Scheme 21). The arylmethylene derivative, e.g., 85, presumably undergoes conversion to a methylene ketene (86, Scheme 22) on pyrolysis, which undergoes a [1,5-H] shift and subsequent cyclization and tautomerization, yielding the dibenzofuranol 87. The derived methyl ether 88 has been converted by mild acetylation with acetyl chloride and aluminum chloride and subsequent boron trichloride-induced demethylation to the natural product ruscodibenzofuran (8). A limitation is imposed on this method because 3-acetyl-2-methyldibenzofurans fail to condense with Meldrum s acid so that l-methyl-3-dibenzofuranols are not available by this method. ... 

Table 11 summarizes the main results on the tautomerism of mono-hydroxy-, -mercapto-, -amino- and -methyl-azines and their benzo derivatives, in water. At first sight the equilibrium between 2-hydroxypyridine (71) and pyridin-2-one (72) is one between a benzenoid and a non-benzenoid molecule respectively (71a 72a). However, the pyridinone evidently has a continuous cyclic p- orbital system, containing six it- electrons, the usual aromatic count, if the carbonyl group contributes none. This assumption implies the formula (72b), from which by redistribution of electrons we arrive at (72c), which has the same benzenoid system as (71a). Further canonical forms (71b, 71c) can be drawn of (71) which correspond to the non-benzenoid forms of (72). The elusive property of aromaticity is therefore possessed by both tautomers, although not necessarily by both equally. When the carbonyl oxygen of (72) is replaced by less electronegative atoms, as in the imine tautomers of amino heterocycles, or the methylene tautomers of methyl derivatives, the tendency towards polarization in forms corresponding to (72b) and (72c) is considerably less, and the amino and methyl tautomers are therefore favoured in most instances. 

The tautomerism of a methyl group a or 7 to a ring nitrogen (86 87) is still less favorable than that of the amine simple valence and electronegativity considerations of the type employed above suggest much reduced aromaticity associated with the methylene tautomer (87). These tautomers are therefore present to only a very small extent at equilibrium. 

Alkyl methyl ketones undergo nitrosation at the reactive methylene group when treated with nitrous acid or an alkyl nitrite [Method (fi)]. The presence of hydrogen on the a-carbon permits tautomeric rearrangement to the oxime of a 1,2-dicarbonyl compound. Acidic hydrolysis of the oxime, which is best carried out in the presence of a hydroxylamine acceptor such as laevulinic acid,143 affords a further useful route to the 1,2-dicarbonyl system. 

H)-OxazoIones (78) are unstable with respect to the 4//-isomers (79) however, the 2-trifluoromethyl derivatives are unique in that the 2//-forms (78 R1 = CF3) are favoured (62LA(658)128). This was evident from the NMR spectra of numerous derivatives containing phenyl or alkyl groups at C(4) (64CB2023). While 2,2-disubstituted 5(2//)-oxazolones (80) have a fixed structure, the 2-methylene derivatives, such as 2-benzylidene-4-methyl-5(2H)-oxazolone (81), are in potential tautomeric equilibrium with 5(4//)-oxazolones, e.g. (82). However, compound (81) exists entirely in this form, no doubt because it is stabilized by conjugation of the phenyl group with the exocyclic double bond. 

Thermally induced rearrangement of quinazoline derivative 8 affords ethyl A -[(6-methyl-l,3-dioxolo[4,5-g]quinazolin-8-yl)methyl]carbamate (9a) in 5 /o yield. Similarly, the thermal and photochemical rearrangement of ethyl A-(6-methyl-8-methylene-l,3-dioxolo[4,5-g]quinazolin-7-yl)-A-phenylcarbamate (7b) produces ethyl A -[(6-methyl-l,3-dioxolo[4,5-g]quinazolin-8-yl)-methyl]-Ai -phenylcarbamate (9b) in 45% yield. Thermal rearrangement of 8, therefore, probably involves the tautomeric methylene base 7a (R = H) as an intermediate. 

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