Benzylic carbons, pyridinium

Tetraphenyl-3//-azepine (2) is formed by the action of sodium hydride on 1-benzyl-2,4,6-triphenylpyridinium tetrafluoroborate (1) in refluxing toluene.37 The 3//-azepine. which arises by attack of the carbanion, generated at the benzylic carbon, at the 2-position of the pyridine ring, is also formed, unexpectedly, in the reaction of the pyridinium tetrafluoroborate with the enolate of ethyl 2-methyl-3-oxobutanoate. 

In a number of nonenzymatic reactions catalyzed by pyridoxal, a metal ion complex is formed—a combination of a multivalent metal ion such as cupric oi aluminum ion with the Schiff base formed from the combination of an amino acid and pyridoxal (I). The electrostatic effect of the metal ion, as well as the electron sink of the pyridinium ion, facilitates the removal of an a -hydrogen atom to form the tautomeric Schiff base, II. Schiff base II is capable of a number of reactions characteristic of pyridoxal systems. Since the former asymmetric center of the amino acid has lost its asymmetry, donation of a proton to that center followed by hydrolytic cleavage of the system will result in racemic amino acid. On the other hand, donation of a proton to the benzylic carbon atom followed by hydrolytic cleavage of the system will result in a transamination reaction—that is, the amino acid will be converted to a keto acid and pyridoxal will be converted to pyridoxamine. Decarboxylation of the original amino acid can occur instead of the initial loss of a proton. In either case, a pair of electrons must be absorbed by the pyridoxal system, and in each case, the electrostatic effect of the metal ion facilitates this electron movement, as well as the subsequent hydrolytic cleavage (40, 43). 

In studies of small molecules, it has been shown that only certain benzylic carbons are reactive enough to form pyridinium salts in refluxing pyridine and iodine (21). There are at least three modes of activating this carbon. 

In the first case [1] Y can be either a hydroxy, alkoxy or nitro group. The first two groups are important but variable constituents in coals and the last is probably minor or non-existent. The second active class of species are the alkyl-pyridines [2]. The final case [3] includes substituents on the benzyl carbon where X can be an ether or carbonyl functional group. The general mechanism of this reaction is most probably the base catalyzed iodination of the benzyl carbon with subsequent displacement of the iodide by the pyridine to form the pyridinium salt. In all three modes of activation, the single aromatic ring can be replaced with polycyclic rings. 

Cationic polymerizations induced by thermally and photochemically latent N-benzyl and IV-alkoxy pyridinium salts, respectively, are reviewed. IV-Benzyl pyridinium salts with a wide range of substituents of phenyl, benzylic carbon and pyridine moiety act as thermally latent catalysts to initiate the cationic polymerization of various monomers. Their initiation activities were evaluated with the emphasis on the structure-activity relationship. The mechanisms of photoinitiation by direct and indirect sensitization of IV-alkoxy pyridinium salts are presented. The indirect action can be based on electron transfer reactions between pyridinium salt and (a) photochemically generated free radicals, (b) photoexcited sensitizer, and (c) electron rich compounds in the photoexcited charge transfer complexes. IV-Alkoxy pyridinium salts also participate in ascorbate assisted redox reactions to generate reactive species capable of initiating cationic polymerization. The application of pyridinium salts to the synthesis of block copolymers of monomers polymerizable with different mechanisms are described. 

Reaction of estrone methyl ether with 2,2-dimethylpropane-l, 3-diol in the presence of a catalytic amount of acid leads to derivative 26-1, in which the ketone at 17 is protected as an acetal (Scheme 3.26). Treatment of this intermediate with pyridinium chlorochromate leads to oxidation of the Cg benzylic carbon atom to a carbonyl group (26-2). Potassium tert-butoxide abstracts a proton from the adjacent methylene at C7 alkylation of the resulting anion with 4-(A, A -dimethyl)butyl iodide gives 26-3 as a mixture of diastereomers. The carbonyl group is next reduced to an alcohol by means of sodium borohydride (26-4). Dehydration of the newly introduced hydroxyl group is arguably facilitated by the adjacent aromatic ring (26-5). Aqueous acid removes the 17-acetal to afford 26-6, which is in essence an equilinin derivative. 

The C2-symmetric epoxide 23 (Scheme 7) reacts smoothly with carbon nucleophiles. For example, treatment of 23 with lithium dimethylcuprate proceeds with inversion of configuration, resulting in the formation of alcohol 28. An important consequence of the C2 symmetry of 23 is that the attack of the organometallic reagent upon either one of the two epoxide carbons produces the same product. After simultaneous hydrogenolysis of the two benzyl ethers in 28, protection of the 1,2-diol as an acetonide ring can be easily achieved by the use of 2,2-dimethoxypropane and camphor-sulfonic acid (CSA). It is necessary to briefly expose the crude product from the latter reaction to methanol and CSA so that the mixed acyclic ketal can be cleaved (see 29—>30). Oxidation of alcohol 30 with pyridinium chlorochromate (PCC) provides alde-... 

Adogen has been shown to be an excellent phase-transfer catalyst for the per-carbonate oxidation of alcohols to the corresponding carbonyl compounds [1]. Generally, unsaturated alcohols are oxidized more readily than the saturated alcohols. The reaction is more effective when a catalytic amount of potassium dichromate is also added to the reaction mixture [ 1 ] comparable results have been obtained by the addition of catalytic amounts of pyridinium dichromate [2], The course of the corresponding oxidation of a-substituted benzylic alcohols is controlled by the nature of the a-substituent and the organic solvent. In addition to the expected ketones, cleavage of the a-substituent can occur with the formation of benzaldehyde, benzoic acid and benzoate esters. The cleavage products predominate when acetonitrile is used as the solvent [3]. 

An intriguing use of a quaternary ammonium salt in a two-phase reaction is to be found with the regeneration of 1 -benzyl-1,4-dihydronicotinamide by sodium dithionite in a biomimetic reduction of thiones to thiols [12], The use of sodium dithionite in the presence of sodium carbonate for the 1,4-reduction of the pyri-dinium salts to 1,4-dihydropyridines is well established but, as both the dithionite and the pyridinium salts are soluble in water and the dihydropyridine and the thione are insoluble in the aqueous phase and totally soluble in the organic phase, it is difficult to identify the role of the quaternary ammonium salt in the reduction cycle. It is clear, however, that in the presence of benzyltriethylammonium chloride, the pyridine system is involved in as many as ten reduction cycles during the complete conversion of the thione into the thiol. In the absence of the catalyst, the thione is recovered quantitatively from the reaction mixture. As yet, the procedure does not appear to have any synthetic utility. 

The catalysts of this ring opening polymerisation reactions are pyridinium salts (for example N-benzyl pyridinium p-toluene sulfonate [75]), p-toluene sulfonic acid [75], stannium or titanium compounds [68-74] etc. Other cyclic polymerisable cyclic carbonates are ethylene carbonate and propylene carbonate [68-74]. 

Acid-catalysed addition of primary, secondary, and tertiary alcohols to 3,4-dihy-dro-2//-pyran in dichloromethane at room temperature is the only general method currently in use for preparing THP ethers and the variations cited below concern the choice of acid. The reaction proceeds by protonation of the enol ether carbon to generate a highly electrophilic oxonium ion which is then attacked by the alcohol. Yields are generally good. Favoured acid catalysts include p-toluenesulfonic acid or camphorsulfonic acid. To protect tertiary allylic alcohols and sensitive functional groups such as epoxides, the milder acid pyridinium p-toluenesulfonate has been employed (Scheme 4.316]. A variety of other acid catalysts have been used such as phosphorus oxychloride, iodotrimethylsilane- and bis(trimethylsilyl)sulfate. but one cannot help but suspect that in all of these cases, the real catalyst is a proton derived from reaction of the putative catalysts with adventitious water. Scheme 4.317 illustrates the use of bis(trimethylsilyl)sulfate in circumstances where other traditional methods failed. - For the protection of tertiary benzylic alcohols, a transition metal catalyst, [Ru(MeCN)2(triphos)](OTf)2 (0.05 mol%) in dichloromethane at room temperature is effective. ... 

Preparation.—A quaternary ammonium anion-exchange resin, in its carbonate form, is the reagent in a new and convenient procedure for the hydrolysis of primary, allyl, and benzyl halides to the corresponding alcohols. A shortened (two-stage) sequence for the conversion of primary alkylamines to alcohols mediated by pyrilium salts (c/. 2,113 4,138) is outlined in Scheme l treatment of the intermediate pyridinium salt (1) with sodium 2-hydroxymethylbenzoate (or thiobenzoate) leads directly to isolation of the alcohol, rather than the esters obtained when sodium acetate or sodium trifluoroacetate are employed. 

Chapman et al. (1974) found that protonated heterocydes including benzthiazolium bromide (102), possessing an alkyl substituent (e.g. benzyl) on the carbon adjacent to the positive nitrogen reacted with methylvinylketone to form adduct (103) which can be converted into fused pyridinium salts (104,105) (Scheme-29) (Chapanan et al. 1974). 

Allylic and benzylic primary and secondary alcohols are more easily oxidized, and a number of reagents selective for these are in use, including freshly precipitated manganese dioxide, silver carbonate, dichlorodicyanoquinone, and potassium ferrate. 4-(Dimethylamino) pyridinium chlorochromate is mild and selective as demonstrated in Equation 6.26 [44]. 

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