Pyridinium intermediate

P-gp) play an active role, and some of these function quite effectively as efflux pumps. One can, therefore, envisage a situation where brain efflux of the pyridinium intermediate competes with in situ activation by hydrolysis. 

In a rearrangement reaction, 2-hydroxy-2-phenyl-2-(3-pyridinyl)acetic hydrazide, 102, reacts with methanesulfonyl chloride to generate a mixture of pyrrolo[2,3-. ]pyridine derivatives (Equation 42) <1998JHG145>. The proposed mechanism for the rearrangement involves intramolecular attack of compound 102 on a reactive pyridinium intermediate formed during the reaction. 

The best catalyst for this transformation was AgSbFg (10 mol%), and (3-ketoesters, malonates, and silyl enol ethers have been used for the nucleophilic addition on the pyridinium intermediate DD. The dihydroisoquinolines 48 have been further used in several reactions in order to assemble the framework of various alkaloids. One example is given in the formation of dihydroisoquinoline 49, bearing a pendent a, 3-unsaturated ketone. Compound 49 can rearrange to the tetracycle 50 (related to the core structure of karachine, Scheme 5.23), using TMSOTf, via a tandem Michael addition-Mannich reaction process (intermediates EE and FF). 

An acylated pyridinium intermediate, indicating nucleophilic catalysis, can be detected in the catalysed hydrolysis of 4-nitrophenyl carboxylates by a dialkylated pyridine attached to laurylated poly(ethylenimine). ... 

In a recent example of p-lactam formation dehydration ofphenoxyacetic acid with 2-fluoro-l-methylpyridinium p-toluenesulfbnate in the presence of diaryhmines is proposed to proceed thorough the pyridinium intermediate 142 which leads to phenoxyketene, which reacts by [2 + 2] cycloaddition with the imine forming the product ds-P-lactam (Eqn (4.87)). Similahly propylphosphonic anhydride (T3P) was also successful in carboxylic acid activation (Eqn (4.88)). 

The first step is the rate limiting step of the reaction (slow reaction) leading to an acyl pyridinium intermediate (1-11), reminiscent of a covalent acyl-enzyme intermediate found in many enzymatic mechanisms. This intermediate is then rapidly trapped by water. 

Silver-mediated Tandem Cyclization to Access Polyheterocycles. A silver-mediated tandem cyclization strategy was employed to access pyrimidine-embedded poly heterocycles. ort/to-Alkynylpyrimidyl aldimines were formed from different amines and AgOTf-mediated 6-endo cyclization with the internal aUcyne furnished pyridinium intermediates. Nucleophilic addition of di-alkylmalonates with the p3uidinium intermediates followed by lactamization afforded various pyrimidine-embedded tricycles in good to excellent yields (eq 79). Grignard reagents could also be added to the pyridinium intermediate. 

Usually, organoboranes are sensitive to oxygen. Simple trialkylboranes are spontaneously flammable in contact with air. Nevertheless, under carefully controlled conditions the reaction of organoboranes with oxygen can be used for the preparation of alcohols or alkyl hydroperoxides (228,229). Aldehydes are produced by oxidation of primary alkylboranes with pyridinium chi orochrom ate (188). Chromic acid at pH < 3 transforms secondary alkyl and cycloalkylboranes into ketones pyridinium chi orochrom ate can also be used (230,231). A convenient procedure for the direct conversion of terminal alkenes into carboxyUc acids employs hydroboration with dibromoborane—dimethyl sulfide and oxidation of the intermediate alkyldibromoborane with chromium trioxide in 90% aqueous acetic acid (232,233). 

The most intensively studied oxidizing system is that developed by Pfitzner and Moflatt in which the oxidation is carried out at room temperature in the presence of dicyclohexylcarbodiimide (DCC) and a weak acid such as pyridinium trifluoroacetate or phosphoric acid. The DCC activates the DMSO which in turn reacts with the carbinol to give an oxysulfonium intermediate. This breaks down under mild base catalysis to give the desired ketone and dimethyl sulfide. 

While this reaction to pyridine 56 occurs in a single pot, it is proposed to proceed via the 1,5-diketo derivative 55 obtained by a Michael addition of the pyridinium species 53 to enone 54. Although one does not typically isolate this intermediate, it has been obtained in reactions of the isoquinolinium series. ... 

Likewise, a cis-2,6-disubstituted piperidine natural product, (-)-lobeline (98, Scheme 8.4.30) was synthesized from the chiral Af-alkyl pyridinium salt ent-80 via a sequence that included addition of a Reformatsky reagent to an intermediate oxazolidine. °... 

An intriguing application of Zincke processes occurred in Marazano s synthesis of dimeric, tetrameric, and even octameric pyridinium macrocycles, including cyclostellettamine B, a sponge-derived natural product. The same strategy produced a synthesis of haliclamine A (121, Scheme 8.4.41), a cytotoxic sponge metabolite. Intermediate 119, itself produced via a Zincke route, underwent an intramolecular Zincke reaction, providing macrocycle 120, which was reduced to the natural product. 

An interesting intermediate 30 was proposed to result from the sequential addition of pyridine to tetrachlorocyclopropene (31). Compound 30 represents an alkyl nitrogen ylide with two 1-chloroalkyl pyridinium moieties in the same molecule. Pyridines with electron-withdrawing groups and heterocycles with an electron-deficient nitrogen, for example, pyridine-3-carbaldehyde or quinoline, react with 31 to yield the corresponding mono-substituted products 32a and 32b (83JOC2629) (Scheme 8). 

Tliionyl halides and A-heteroaromatics are known to be in equilibrium with the corresponding A-(halosulhnyl)heteroarylium halides. N-(Chlorosulhnyl)pyridinium chloride (36), for example, readily reacts with a second molecule of pyridine to give the A-[l-chlorosulhnyl-l,4-dihydro-pyridine-4-yl]pyridinium chloride (37a). The intermediate 37a is probably involved in the preparation of A-(pyridine-4-yl)pyridinium chloride hydrochloride (37b). However, the authors could not detect either 37a or 37b in their experiments (91CB2013) (Scheme 10). 

Reaction of pyridinium-A -(2-pyridyl)amidine (402) and alkyl haloace-tates in the presence of K2CO3 afforded a mixture of 4-oxo-4/f-pyrido[l, 2-u]pyrimidine-2-carboxylates 407 and 2-aminopyridine derivatives 406 through intermediers 403- 05, as depicted in Scheme 15 (00TL5837). Compound 406 could be cyclized on the action of heat or silica gel into 407. The best yield was achieved in the case of ethyl bromoacetate. 

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