2.4.6- Triaryl pyridines

Isoquinolinium salts (2) derived from a-bromo-ketones undergo Michael addition to ajS-unsaturated ketones in acetic acid, in the presence of ammonium acetate, to give 2,4,6-triaryl-pyridines (3) in yields ranging from 40 to 60% (Scheme 2). ... 

In 1999, Katritzky reported a novel [3+2+1] synthesis of 2,4,6-trisubstituted pyridine derivatives that used the Michael addition of a-benzotriazolyl ketones to a,P-unsaturated carbonyl compounds. This reaction resembles the Krohnke pyridine synthesis and is an extension of Katritzky s earlier studies with benzotriazolyl derivatives that provided access to pyridones, 2-thiopyridones, 5-alkyl-2,4-diphenylpyridines and 2-aminopyridines. This approach is attractive as both components are readily synthesized or commercially available. The availability of these starting materials allows for an efficient access to structurally diverse 2,4,6-triaryl pyridines when combined with ammonium acetate in acetic acid at reflux. In addition, it is possible to access fused 2,3,4,6-tetrasubstituted pyridines from the requisite fused bicyclic ketone starting material. The preparation of the pyridine ring via benzotriazole methodology has resulted in improved yields for many compounds and the opportunity to synthesize molecules with a substitution pattern that would be difficult to prepare by other methods. 

Shafiee, M. R. M. and Moloudi, R. 2011. Solvent-free preparation of 2,4,6-triaryl pyridines using silver(I) nitrate adsorbed on silica gel nanoparticles (AgN03-nano-Si02) as an efficient catalyst. Left. Org. Ghem. 8(10) 717. 

Scheme 4 Magnesium-enabled formation of 2,4,6-triaryl pyridines.

The using of chalcones, ketones, and ammonia as substrates with magnesium methoxide as the promoter to synthesis pyridines was described in 2013 [82], Fair to good yields of the corresponding 2,4,6-triaryl pyridines have been formed in MeOH (Scheme 3.38). More recently, the combination of ceric ammonium nitrate (10mol%) and pyrrolidine (20mol%) as the catal5dic system was explored for this transformation as well [83]. 

In the presence of 70% perchloric acid at 100 °C, the acetophmiones Ar COMe (Ar = C Hs or CeFj) react with the benzaldehydes Ar CHO (Ar = C Hs or C(Fg) during 10 min to give the chalcones (72), but reaction during 2 h yields the pyiylium perchlorates (74 Ar = Ar ), which may also be obtained from the chalcones and perdiloric add or, in better yield, from the chalcones and the appropriate acetophenone Ar COMe (Ar = CfHg or C Fs) in the presence of perchloric acid. A mechanism for these condensations has been outlined (Scheme 19), and the pyrylium salts yield triaryl-pyridines (73) on treatment with ammonium carbonate in acetic acid. ... 

Values of ka and b are correlated by the Hammett equation for pyridines and for triaryl phosphines. Very large negative p values were found for pyridine reactions especially (35). Key values are highlighted in Table II. 

Triaryl esters can be prepared by a variety of methods. For example, by allowing 3 mol. of the phenol to react with 1 mol. of phosphorus oxychloride for several hours. Organic bases such as aniline, dimethylaniline and pyridine have been used to neutralize the hydrogen chloride formed in the reaction.3 Alternatively, the phenols may be converted into the sodium phenoxides4 and then allowed to react with phosphorus oxychloride. 

The sterically hindered base 2,6-bis(tert-butyl)pyridine does not inhibit cyclization triaryl-amine retards this reaction photosensibilized one-electron oxidation of a diene leads to the same products, which are formed in the presence of ammoniumyl salt. As shown, in majority of cases, only the cation-radical chain mechanism of the diene-diene cyclization is feasible (Bauld et al. 1987). Meanwhile, cyclodimerizations of 2,4-dimethylpenta-l,3-diene (Gassman and Singleton 1984) and l,4-dimethylcyclohexa-l,3- or -1,4-diene (Davies et al. 1985) proceed through both mechanisms. 

Pyrylium salts, especially the 2,4,6-triaryl substituted, react with a wide variety of nucleophiles some of which lead to the formation of rings other than benzene or pyridine. Sodium sulphide, for instance, attacks the pyrylium ring at C-2 to produce the blue-coloured dienone (78) which then cyclizes on treatment with add to the thiopyrylium salt (79) (56HCA207). 

Similar reactions have been reported for a mixture of 2,6-dimethoxyi-odobenzene, copper(I) oxide, and 1,3,5-trinitrobenzene in pyridine 21). Di- and triarylation can be effected under suitable conditions of catalyst, solvent, and temperature. No simple hypothesis can explain the experimental facts for the copper(I) oxide reactions. 

Wu and co-workers [77] have developed a novel, simple and efficient method for the synthesis of 2,4,5-triaryl-5//-chromeno[4,3-h]pyridines 37 under microwave radiation via a three-component cascade reaction of 2-hydroxyacetophenone, an aromatic aldehyde and ammonium acetate catalyzed by 2-l -methylimidazolium-3-yl-l-ethyl sulfate. When an insufficient amount of (or no) catalyst was used, solely the corresponding chalcone was formed. Nine new bonds and two new rings are generated in a one-pot process with water as the only byproduct (Scheme 26). 

Diaryl methyl- and benzyl-phosphonates are conveniently prepared in high yields by heating mixtures of triaryl phosphites, methanol or benzyl alcohol, and a trace of methyl or benzyl halide. In a reaction that is usefully complementary to the previously reported formation of pyridine-2-phosphonic acid derivatives from sodium dialkyl phosphonates and //-methoxypyridinium compounds ( Organophosphorus Chemistry , Vol. 7, p. 111), N-triphenylmethylpyridinium tetrafluoroborate affords the pyridine-4-phosphonic dialkyl ester when heated with sodium dialkyl phosphonates. ... 

Carboxylation of the potassium salt of 3-hydroxy-6-methylpyridine (145) gave the picolinic acid 146(84MI16). The Hammick condensation reaction of picolinic acid with benzaldehyde has been studied with regard to the effect of solvent, temperature, and molar ratio of reactants (85MI5). Benzoyl chloride, or benzaldehyde, and l-benzyl-4,6-diphenylpyridinium-2-carboxylate afford 2-benzoyl-4,6-diphenylpyridine (85JCS(P1)2167). Sulfur and 1,4,6-triaryl-pyridinium-2-carboxylates 147 in xylene at 140°C give the corresponding pyridine-2-thiones 148(838149). 

We have also shown that phosphites4), especially diphenyl and triaryl phosphites react non-oxidatively with carboxylic acids in the presence of pyridine to give acyl-oxy N-phosphonium salt of pyridine (5 and 6 in Scheme 2) accompanied by dephen-oxylation, which produces the corresponding amides and esters on aminolysis and alcoholysis. The structure of N-phosphonium salts such as 5 and 6 is presumed to result from the stoichiometric relationship among phosphites, pyridine, and the car-boxy component. 

Though the preparation of polypeptides directly from free amino acids is very difficult because of their tendency to give cyclic dimers (dioxopiperazines) by ordinary methods22, we have succeeded in obtaining linear polypeptides with relatively high molecular weights by the direct polycondensation of a-amino acids through the use of diphenyl and triaryl phosphites in pyridine. We have also obtained polypeptides with ordered sequences by the indirect polycondensation of activated derivatives of peptides, such as their active esters by ordinary methods, directly from unactivated dipeptides (Table 13)23. ... 

Aryl isothiocyanates cyclize with 2-amino-4,6-diarylnicotinonitriles in pyridine/dioxanc120 or potassium hydroxide/dimethylformamide90 to give 3,5,7-triaryl-2-sulfanylpyrido[2,3-r/]pyrimidin-4(3//)-imines 61, the intermediate pyridyl thioureas not being isolated. 

Diary] and triaryl or naphthyl carbamates exhibit low herbicidal activity. The substitution of the aryl radical for a heterocyclic radical gives heterocyclic alkyl and dialkyl ureas, of which many examples have been prepared in recent years. The herbicidal activity of urea derivatives containing a heterocyclic radical, such as benzthiazole, thiazole, thiadiazole, oxadiazole and pyridine, is favourable if one or two methyl groups are substituted at the N -nitrogen. The carrier of total or selective action in these derivatives is presumably the heterocyclic part of the molecule. More recently several new groups of compounds have become known, mainly in the patent literature, for which the structure-activity on relationships are still to be elucidated. 

Trimerization of nitriles, isocyanates, isothiocyanates, imidates, and carbodiimides all lead to symmetrical 2,4,6-trisubstituted 1,3,5-triazines (see Section 6.12.9.5). The use of lanthanide trifluoromethanesulfonate and ammonia as cocatalysts is claimed as a big improvement. The trisaminal of 2,4,6-triformyl-l,3,5-triazine is also useful for further derivatization to unusual structures (see Section 6.12.7.1). Treatment of a 1 1 pyridine/conc. ammonia solution of an aromatic aldehyde with excess Fremy s salt is another development. Separation of the amide coproduct was claimed to be easy. The synthesis fails with aliphatic aldehydes (see Section 6.12.9.5.4). Aminolysis of 2,4,6-triaryl-1,3,5-oxadiazinium salts gives symmetrical 1,3,5-triazines but the reactions are limited in that electron-withdrawing groups in the aromatic rings lead to instability and difficulty in separation of products (see Section 6.12.10.4). 

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