Pyridines with Lewis acids

Wang Z, Liu Z, Ding X, Yu X, Hou B, Yi P (2012) Comparisons of the halogen-bonded and hydrogen-bonded complexes of hiran, thiophene and pyridine with Lewis acids (CIF, HCl). Comp Theor Chem 981 1-6... 

Because of the presence of a lone pair and a vacant orbital, singlet carbenes are supposed to be able to react with both Lewis bases and acids. Transient electrophilic carbenes are known to react with Lewis bases to give normal ylides (Scheme 8.19). For example, carbene-pyridine adducts have been spectroscopically characterized and used as a proof for the formation of carbenes,and the reaction of transient dihalogenocarbenes with phosphines is even a preparative method for C-dihalogeno phosphorus ylides. Little is known about the reactivity of transient carbenes with Lewis acids. 

Allylic carboxylation. Diethyl oxomalonate (1) undergoes a thermal ene reaction with mono-, di-, and trisubstituted alkenes at 145 180°. The reaction is also subject to catalysis with Lewis acids, which can lead to a different ene product. The products are a-hydroxymalonic esters. The corresponding malonic acids are converted to carboxylic acids by bisdecarboxylation with NaI04 and a trace of pyridine- or with ceric ammonium nitrate (CAN). Diethyl oxomalonate then functions as an cnophilic equivalent of C02. 

To prove their hypothesis, Bamford and Block (51) applied the diagnostic test previously designed by Gold and Jefferson (58) in their studies of hydrolysis of carboxylic anhydrides catalysed by tertiary bases. The technique employed involves the use of a series of tertiary bases having different relative abilities to assodate with Lewis acids and to act as Bronsted bases. Pyridine, a-picoline and 2,6-lutidine form... 

Br0nsted acid sites depends on the structure of the amine. Chemisorption data for amorphous oxides (54) show that 2,6-dimethylpyridine (which contains methyl groups that hinder coordination of the nitrogen atom with Lewis acids) is a more selective reagent for the determination of Br0nsted acidity than an unhindered amine such as pyridine. Jacobs and Heylen (44) arrived at a similar conclusion on the basis of an infrared study of amines chemisorbed on Y zeolite. They also found that the poisoning effectiveness of 2,6-dimethylpyridine is much greater than that of pyridine for the catalytic titration of Y zeolite. 

Infrared spectral studies of pyridine adsorbed on alkali metal ion-exchanged faujasites have demonstrated the absence of Brpnsted acidity, as reported by Eberly (151), Ignat eva et al. (208), and Ward (156, 209-211). Pyridine is adsorbed weakly by coordination to the alkali metal ions (151, 156). Addition of small amounts of water does not result in formation of Br0nsted acid sites, indicating that the coordinate bound pyridine is not associated with Lewis acid sites in the zeolite framework (210). 

Infrared absorption can be used to estimate the relative amounts of Lewis and Bronsted acid sites on cracking catalysts. Bases complex with Lewis acid sites while proton transfer to the base occurs at Bronsted acid sites. Each has distinct, well-resolved infrared bands. For example, pyridine forms a complex with the Lewis acid site and produces an infrared absorption band at approximately 1450 cm-1. Pyridinium ions form at Bronsted sites and produce an absorption band at approximately 1540 cm-1. The relative intensities of these two bands can be used to estimate the relative amounts of Lewis vs. Bronsted acid sites. 

Examples of electrophilic attack on N-protected 1,2-dihydropyridines include bromine-mediated addition of Boc-protected-guanidine 534 to dihydropyridine 533 giving, after acid deprotection, f-2-amino-l,3a,S,7a-dihydroimidazo [4,5- ]pyridine 535 <2004OL3933> formation of 5-trichloroacetyl-l,4-dihydropyridines 536 <2003TL4711> and -formylation with the Vilsmeier reagent <20060L179>. -Aminonitriles which are formed by trapping 2,3-dihydropyr-idinium salts with cyanide ion are stable, but easily converted back into 2,3-dihydropyridinium salts with Lewis acids. 

Salicylaldehydes and 2-pyridine carboxaldehyde which cannot be normally used with Lewis acids because of their coordination to metal may be used as substrates with Lu triflate as a catalyst [156]. 

A different behavior is found when strong nucleophiles are added to a polymerization of isobutene coinitiated with Lewis acids. When the concentration of nucleophile reaches that of Lewis acid, no polymerization is observed [5,91,268]. Quite often a precipitate, identified as a complex between Lewis acid and the nucleophile, is detected. This indicates that the complexed Lewis acid is no longer capable of ionization of the covalent species. A fractional negative order (-0.3) was reported in the polymerization of isobutene initiated by alkyl chloride/TiCL with added pyridines [268]. It is possible that a small amount of pyridine complexes with the Lewis acid, reduces its concentration, and thereby additionally shifts the equilibria from the more reactive dimeric to the less reactive monomeric TiCI4. Nevertheless, a small amount of nucleophile apparently has a beneficial effect, because polymers with lower polydispersities are formed. The plausible explanation of the role of nucleophiles in these systems will be offered in Section VILE.4. 

Investigations on the trimerization of phenylcyanamide have shown that either triphenylmelamine (12) or triphenylisomelamine (13) is formed, depending on the reaction conditions.1 19,230,231 Under mild conditions (20-80°C) and in the presence of basic catalysts (e.g triethylamine, pyridine) the iso form 13 is obtained, whereas with Lewis acids [e.g., zinc(IT) chloride, titanium(IV) chloride] at 200 °C, triphenylmelamine (12) is formed. 

Within the series of Mg-Fe mixed oxides, no Bronsted acid sites are detected. Pyridine interacts essentially with Lewis acid sites and disappears almost completely after evacuation at temperatures higher than 21°C, indicating the weak nature of this bonding. The acid sites are coordinatively unsaturated Fe (octahedral) cations pairs of coordinatively unsaturated Fe in octahedral and tetrahedral coordination are also present in the samples at lower Mg/Fe atomic ratio. With increasing Mg/Fe ratio, a decrease in the total Lewis acid sites density is observed. The MgO single oxide, like the Mg/Al=2.0 mixed oxide, does not show the presence of any acid sites able to chemisorb pyridine. The acidity in the Fc203 samples was not detected because of the poor transparency of this material in the IR region. 

Pyridine-iV-oxides form stable 1 1-complexes with Lewis acids. The SbCl5 complexes 82, on thermolysis followed by hydrolysis, yield 2-pyridones by a regioselective transfer of oxygen to the a-position via 83. 

Further studies of the reaction of molybdenum and tungsten carbonyl complexes with Lewis acids have been reported and several interesting new adducts characterized. [Mg(py)4][(7r-Cp)Mo(CO)3]2 has been obtained by a metal-exchange reaction from [Hg Mo(7t-Cp)(CO)3 2] in THF, followed by recrystallization from pyridine. X-Ray crystallographic studies have shown the compound to possess the units (67), the dimensions of which suggest that an... 

Although they are not as widely used as pyridine, substituted pyridines have found their own place in the characterization of hydroxyl groups. It was proposed (470) that, for steric reasons, 2,6-dimethylpyridine (DMP, lutidine) does not interact with Lewis acid sites and is thus a proton-specific probe. Later, it was demonstrated that DMP (247,256,471-473) (as well as 2,4,6-trimethyl pyridine or collidine (474)) stiU forms coordination bonds with coordinatively unsaturated surface cations. This bond is only weakened by the steric interference of the methyl groups with the surface but not prevented. In any case, the steric hindrance leads to preferential interaction ofDMP with hydroxyl groups (471-473). DFT calculations suggest that the proton transfer is promoted by the stabilization of the lutidinium ion on the deprotonated site, rather than by the intrinsic acidity of the acid site itself (475). 

A widely used class of compounds are pyridine and alkylpyridines, including 2,6-lutidine, 2,4,6-coUidine, DTBP, quinoline, 4-methylquinohne, and 2,4-dimethyl-quinoline (565,582). These molecules interact with acidic hydroxyls through their N-atoms with formation of protonated species. Because they are strong bases, the possibility to extract protons from their original positions cannot be ruled out. An advantage (but in some cases disadvantage) of many pyri dines with bulky substituents is that, for steric reasons, they do not interact with Lewis acid sites through the N-atoms, or this interaction at least is hindered. 

Pyridines can also be constructed by the Diels-Alder reaction of azadienophiles, such as nitriles or imines, and dienes. Imines usually need to be activated with Lewis acids such as Yb(OTf)3, ZnCL, and EtzAlCl. 

Whether a Lewis acid is capable of initiating these polymerizations by itself was tested, with the aid of an early discovery. It has been known for some time that hindered bases like crowded pyridine derivatives exhibit specificity toward reactions with protons. Such bases might be used to discriminate between two types of initiating mechanisms encountered with Lewis acids. The base will not interfere with direct electrophilic additions of the Lewis acids to the monomer. On the other hand, it should prevent an initiation process by protons from taking place. If both pathways are operative, then the pyridine derivatives can only quench the protonic initiation and will offer a means of assessing the relative importance of each process. 

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