Intermediates pseudobases

According to these results, it was assumed that transfer of a hydride anion from the intermediate pseudobases 22 and 23 to 16 occurs, which would explain the formation of all reaction products conclusively (79T2591). 

A(,fV-Dimethylamino)perhydro-2-thioxo-l,3-thiazin-4-one (141) reacts preferentially with many nucleophiles at the carbonyl group thus with piperidine, for example, it affords the N- N,N-dimethylamino)dithiocarbamate (142), probably via the intermediate pseudobase (143) (Scheme 26)... 

The ANR reaction involves a double reduction at the C-2 and C-3 of the anthocyanidin, allowing the inversion of C-3 stereochemistry. Xie et al. postulate four possible reaction mechanisms, proceeding via either flav-3-en-ol or flav-2-en-ol intermediates. The proposed reaction mechanisms are based on anthocyanidins (the flavylium cation forms) as the starting molecules however, as the authors acknowledge, other forms of the anthocyanidin may exist in vivo. In particular, the 3-flaven-2,3-diol pseudobase is thought to be the more likely in vivo product of the ANS. 

This result confirmed the mechanistic interpretation of the Decker oxidation suggested by Abramovith (71 JCS(B) 131). The intermediate complex 57 is oxidized to 48, which implies the introduction of the pyridone carbonyl function into the originally substituted C-2 position of the heterocycle (Scheme 12). These results have also been confirmed by Nesvadba and Kuthan (83CCC511). With increasing concentration of alkali, a C-6 pseudobase is... 

The direct substitution of the added nucleophile was described (76JA5581) for 114 with 124 as the final product two authors postulated that the dissociation of the primary adduct takes place with the intermediate formation of cation 30. Heating of the pseudobase 114 without nucleophiles leads to the acetal dimer 125. 

The existence of a deprotonated form 242 as intermediate, together with pseudobase 243, was assumed in this case, but the betaine was so shortlived that even its electronic absorbtion spectrum could not be measured. Deprotonation of the 6-hydroxyl group was preferred for salt 10 (R1 = H) having another hydroxyl group in the l-aryl substituent [75ACH(85)79], and betaine 245 was formed in spite of the possibility of alternative deprotonation, which would have conserved aromaticity in the annelated ben-zenoid ring, as in 246 (R1 = H). 

Diketones 29 are not intermediates in the formation of chrysenes because under the reaction conditions they form only a-naphthols 204, which are products of intramolecular cyclization. The real intermediate for chrysene formation is the anhydrobase 267. The key role of this compound is supported by the isolation of the dimeric pseudobase 269 (85KGS910), as well as by trapping of the latter compound with the proton sponge, which possesses pronounced basic properties (68CC723). 

The formation of acyl-chrysenes 270 from 1-methyl-substituted ben-zo[c]pyrylium salts 266 occurs not only on heating in alkaline solutions, but also in acidic nucleophilic media (cf. Section III,C,4,b,i). However, in the latter case, together with acylchrysenes 270, their deacylated analogs 273 are formed (85KGS910). Under these conditions, the same results were obtained for conversions of diketones 29, therefore it is difficult to conclude which compound (anhydrobase 267 or diketone 29) is the intermediate in the formation of chrysenes 270 and 273 from salts 266 in acidic nucleophilic medium. It was not possible to trap or detect the dimeric pseudobase 269 under these conditions. However, the latter compound, under the described conditions or on heating in acetic acid, forms the mixture of the same products (270 and 273). 

Heterocyclic cations will not easily react with electrophiles unless substituted by strongly electron-releasing groups. Alternatively, the reaction conditions are chosen in such a way that a reactive anhydro base or pseudobase intermediate is formed. Thus the thiazolo cation (336) can be nitrated at C-3 (78ZOR216) possibly via the ylide (337). The 6(8)-nitro-2,3-dihydrothiazolo[3,2-a]pyridinium salts (338) and (340) are readily brominated in hydroxylic solvents the regioselectivity and the ease of reaction are consistent with pseudobase intermediates (339) and (341) <81H(15)1349). 

Other cation-pseudobase equilibrations that have received detailed spectral investigation include quaternary isoquinoline alkaloids and related isoquinolinium derivatives,910 naphthyridinium mono- and dications,26,38,42 44 50 pyridinium cations,51,52 isobenzopyrylium (isochro-mylium) cations,53 benzothiopyrylium (thiochromylium) cations,40 and 1,3-dithiolium cations.54 PMR spectroscopy has also been useful in the identification of pseudobases as reaction intermediates in several reactions in solution.55-57 While 13C-NMR spectroscopy is also potentially useful for the assignment of pseudobase structure, at present there do not appear to... 

The following sections will emphasize those systems in which reasonable attempts have been made to conduct detailed investigations of ring-opening reactions of pseudobases in aqueous solution. In addition, there are numerous reactions of heterocyclic molecules, under a wide variety of reaction conditions, which have been postulated to proceed via ring-opening of a pseudobase intermediate.100-194-20 3... 

The 1,3-benzodithiolium and 1,3-benzoxathiolium cations undergo ring-opening reactions readily in aqueous solution. For the parent 1,3-benzodithiolium cation (90), the pseudobase intermediate (91) has been identified by PMR spectroscopy,55 with the ultimate product 93 from this cation being formed by the addition of one ring-opened thiolate anion to another cation.55,256 The 2-phenyl-1,3-benzoxathiolium cation... 

The best-studied example of this phenomenon appears to be the situation in aqueous solutions of thiazolinium cations discussed in Section V,A,4. Only C—O bond cleavage is observed for the pseudobase 104 of the Af,0-trimethylenephthalimidium cation164 although the products obtained from the tetrahedral intermediate 106 of the iminolactone 105 are... 

There are many examples in the literature of reactions of heterocyclic molecules which have been postulated to proceed via pseudobase intermediates. While most of these reaction mechanisms seem to be chemically reasonable, in most cases the participation of the pseudobase in the reaction has not been definitely established by kinetics, spectral studies, substituent... 

The bromination of various nitrogen heterocycles has been shown to proceed via pseudobase or covalent hydrate intermediates. Tee et a/ 37.100,294... 

Pseudobases have often been postulated as intermediates in the chemiluminescent oxidation of acridinium cations to acridinones.103-297 299 Both the mono- and dipseudobases (156 and 157) of lucigenin have been proposed as intermediates in the chemiluminescent oxidation of this cation in basic solutions. 

Various decomposition reactions of heterocyclic cations in aqueous solution are expected to proceed via pseudobase intermediates. These intermediates have been established for the alkaline decomposition of the pyridinium ring of nicotinamide adenine dinucleotide300 and for various solution transformations of flavin-derived cations.112,113,301-303 Nucleophilic substitution by hydroxide ion in various heteroaromatic cations almost certainly proceeds via the appropriate pseudobase tr-complexes.304,305... 

Pseudobase formation by nucleophilic addition to heteroaromatic cations is closely related to the long-known Meisenheimer complex formation by nucleophilic addition to an electron-deficient neutral aromatic molecule.20-25 In both cases nucleophilic attack on an electron-deficient aromatic ring produces a c-complex—an anionic Meisenheimer complex or a neutral pseudobase molecule. Despite the intense interest over the past few years in Meisenheimer complexes as models for er-complex intermediates in nucleophilic aromatic substitution reactions, there has been little overt recognition of the relationship between Meisenheimer complexes and pseudobases derived from heteroaromatic cations. In this regard, it is interesting that the pseudobase 165, which can be regarded as the complex intermediate that would be expected for an SNAr reaction between the l-methyl-4-iodoquinolinium cation and hydroxide ion, has been spectroscopically characterized.89... 

In aqueous media, most of the natural anthocyanins behave like pH indicators, being red at low pH, bluish at intermediate pH, and colorless at high pH. According to Brouillard (1982), in acidic and neutral media four anthocyanin structures exist in equilibrium the red flavylium cation (AH+), blue or red quinonoidal base (A), colorless carbinol pseudobase (B), and colorless chalcone (C) (Reaction 9.3). 

Afs,(V10-Dialkylisoalloxazines react with molecular oxygen to give 4a-hydroperoxides (43a), which provide, on spontaneous decomposition, 4a-pseudobases (43b). These intermediates undergo ring contraction in basic medium to yield spirohydantoins (44).87... 

In the case of azapetine (12) and nicotine (13), the iminium ion intermediate rather than the carbinolamine appears to be the form of substrate preferred by aldehyde oxidase [63-66]. On the other hand, the ring-opened aldehyde intermediate (aldophosphamide) (14) of cyclophosphamide is oxidized by the enzyme [67], although the isomeric 4-hydroxycyclophos-phamide (15) also undergoes oxidation by a soluble fraction enzyme [11]. Oxidation of the carbinolamine form to a cyclic lactam would not seem to involve nucleophilic enzyme attack, and yet we have shown that the stable pseudobase of 3-methylquinazolin-2-one (16), is an efficient substrate of aldehyde oxidase and competitively inhibits the oxidation of both quaternary and non-quatemized substrates [62]. 

A novel route to the rhoeadines starts with the readily available immonium salt 13 which was subjected to Schotten-Baumann conditions the aldehyde 15 was formed in 91% yield via the intermediate A-benzoylated pseudobase 14. Intramolecular aldol condensation of the aldehyde was induced by a strong base, thus generating the lactonic rhoeadine amide 16 in 56% yield. This short series of transformations represents a new benzazepine synthesis. 

Thiamin is unstable in alkaline solutions (Figure 5.3A) in the pH range 8-10, hydroxyl attack on C-2 of the thiazolium ring leads to the relatively slow formation of a pseudobase intermediate (compound 2 in Figure 5.3) and the... 

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