Picolinium

A) Preparation of 1-Methyl-2-Picolinium Chloride 98 ml of cx-picoline is dissolved in 200 ml of methanol, cooled and 85 ml (at -68°C) of methyl chloride is added. The solution is charged to an autoclave, sealed and the nitrogen pressure of 300 psig is established. The mixture is heated at 120° to 130°C for 2 hours, cooled and opened. The resulting solution is then evaporated to dryness in vacuo, yielding a residue of 110 g. This residue is then dissolved in 50 ml of water and extracted with two 50 ml portions of ether. The aqueous phase is then diluted to 150 ml with water and an assay for ionic chloride is performed which indicates the presence of chloride ion equivalent to 721 mg/ml of 1-methyl-2-picolinium chloride. 

B) Preparation of 2-(Hydroxyiminomethyl)-1-Methyl Pyridinium Chloride An aqueous solution of 15 ml of 1-methyl-2-picolinium chloride having a concentration of 477 mg/ml Is covered with 50 ml of benzene in an atmosphere of nitrogen and cooled to below 10°C. An aqueous solution of sodium hydroxide is added dropwise and the mixture is stirred for 5 minutes and allowed to stratify. The aqueous phase Is then drawn off and the benzene solution is added slowly to a solution of 3 ml of nitrosyl chloride in 175 ml of benzene containing 0.5 ml of dimethyl formamide at about 10°C in an atmosphere of nitrogen with good agitation. The mixture is then stirred for 1.5 hours and then extracted with four... 

We have also used j3-picolinium-p-chlorophenacylide ()3-PCPY) [15], a cycloimmonium ylide, as the radical initiator for the polymerization of MMA [18,19] at 60-70°C. (See also Table 1.) The kinetics of the system has been studied. 

Figure 14. Modification of charge density on carbon atoms of benzylpicolyl-magnesium and a-picolinium chloride calculated from C-13 NMR.

Another elegant approach to alkyl- and aryl-substituted quino-lizines involves the condensation of a-picolinium salts carrying an active methylene group on the nitrogen atom with suitable a-diketones. Westphal et al,11 have reacted 1,2-diketones, e.g. diacetyl, benzil, furil, and pyridil, with 2-methyl-A-carbethoxymethylpyridinium halides in the presence of weak bases such as dibutylamine or sodium bicarbonate and obtained the corresponding 2,3-disubstituted quino-lizinium halides [Eq. (3)]. Spontaneous hydrolysis and decarboxylation... 

N-, 0-, and S-heterocyclic ligands also form [Os(NH3)5 t)2-(C,C)-L ]2+ complexes [L = 2,6-lutidine, 2,6-lutidinium, pyridinium, N-methylpyridinium, and lV-methyl-4-picolinium (85, 167), NJV -dimethylimidazolium (90), pyrrole (90, 179), IV-methylpyrrole (90, 179), thiophene (90,179), furan (90,179), and 1,3-dimethyluracil (72, 73)]. On oxidation to Os(III), arene ligands are rapidly lost from the coordination sphere, or in the case of the substituted arene ligands with good a donors, rapid linkage isomerization reactions occur (Section V,D). 

Two intermediates, (125) and (126), were proposed for the conversion of l-phenacyl-2-picolinium bromide into a mixture of the phenylindolizines (127 R = H) (Scheme 19). The enol betaine (126) has been shown to be an intermediate by an independent synthesis. It may be noted, however, that the benzoylation of the lutidine analogue at room temperature gave the enol benzoate (128) which on treatment with base yielded the expected indolizine (127 R = Me) (72CB2344). 

Pesticides. The compound 2-picoline is a component of l-[(4 -amino-2/- f-propyl-5 -pyrimidinyl )methyl]-2-picolinium chloride hydrochloride, known as Amprolium, a broad-spectrum coccidiostat. A newer coccidiostat is 3,5-dichloro-4-hvdToxy-2,6-lnfidine and known... 

Kreutzberger and Abel36 showed that treatment of />-nitrobenzyl-a-picolinium chloride (7a) with j-triazine in pyridine gave an 8% yield of the cyclized indolizine (9), presumably via the resonance-stabilized intermediate 8 (see Scheme 3). 

In a reaction somewhat similar to that of Tschitschibabin, N-propargyl-2-picolinium bromide was cyclized by base to 2-methylin-dolizine, but the yield was poor compared to that of the 1-aza analog prepared by a similar route.37,38... 

When a highly activated methylene group is present [e.g., in the conversion of l-phenacyl-2-picolinium bromide (19) into a mixture of 3-benzoyl-2-phenylindolizine (20) and l-benzoyl-2-phenylindolizine (21) using benzoic anhydride and triethylamine] the reaction could proceed through either of two intermediates, 22 or 23 (Scheme 5). Melton and... 

Carbohydrate metabolism provides the main energy source in coccidia. Diets deficient in thiamin, riboflavin, or nicotinic acid—all cofactors in carbohydrate metabolism—result in suppression of parasitic infestation of chickens by E tenella and E acervulina. A thiamin analog, amprolium—1-[(4-amino-2-propyl-5-pyrimidinyl)-methyl]-2-picolinium chloride—has long been used as an effective anticoccidial agent in chickens and cattle with relatively low host toxicity. The antiparasitic activity of amprolium is reversible by thiamin and is recognized to involve inhibition of thiamin transport in the parasite. Unfortunately, amprolium has a rather narrow spectrum of antiparasitic activity it has poor activity against toxoplasmosis, a closely related parasitic infection. 

It has been mentioned ( 4.4.2) that nitronium tetrafluoroborate reacts with pyridine to give i-nitropyridinium tetrafluoroborate. This compound and several of its derivatives have been used to effect what is called the transfer nitration of benzene andtoluene.461 -Nitropyridinium tetrafluoroborate is only sparingly soluble in acetonitrile, but its homologues are quite soluble and can be used without isolation from the solution in which they are prepared. 1-Nitropyridinium tetrafluoroborate did nitrate toluene in boiling acetonitrile slowly, but not at 25 °. In contrast, i-nitro-2-picolinium tetrafluoroborate readily... 

Figure 3.20. Analysis of carboxylic acids and alcohols by reversed phase HPLC, with indirect UV detection, (a) Carboxylic acids. Chromatography conditions mobile phase, 3 X 10 4 M l-phenethyl-2-picolinium in acetate buffer (pH 4.6) column, ju-Bondapak phenyl detection, indirect UV absorbance at 254 nm. Peaks 1, acetic acid 2, propionic acid 3, butyric acid 4, valeric acid 5, caproic acid S, system peak, (b) Aliphatic alcohols. Chromatography conditions mobile phase, 4 x 10 4 M nicotinamide in water column. Ultrasphere ODS detection, indirect UV absorbance at 268 nm. Peaks 1, methanol 2, propylene glycol 3, ethanol 4, 2-propanol 5, 1-propanol 6, system peak 7, 2-butanol 8, 2-methyl-l-propanol 9, 1-butanol. (Redrawn from Refs. 23 and 24 with permission.)...

An efficient combinatorial solid-phase synthesis of asymmetric cyanine dyes was developed by Isacsson and Westman [17] using a Rink amide polystyrene resin. The picolinium and lepidinium salts 6 were linked to the solid-phase resin by amide coupling, then the benzothiazole derivatives 7 were subsequently condensed with the coupled picoline and lepidine moieties to give the yellow to blue (Amax ahs = 420-590 nm) asymmetric, fluorescent (Amax em = 480-650 nm) cyanine dyes 8 (Scheme 5.2, Fig. 5.3). As a consequence of restricted rotation upon intercalation, the fluorescence quantum yields increase significantly when these dyes are bound to DNA. 

Fig. 5.4 Selected aldehyde (9) and picolinium building blocks (10) for the combinatorial synthesis of stilbazolium salts.

Two other nucleophilic substitution reactions of pyridine iV-oxides deserve mention and further study to determine the effects of substituents. Pyridine N-oxide, benzoyl chloride, and the piperidine enamine of cyclohexanone give a good yield of 2-(2 -pyridyl)cyclo-hexanone (155) (63%).360 When W-methoxy-4-picolinium methyl... 

N(CH2Ph)R3 1 -R-pyridinium 1-R-picolinium 1 -PhCH--pyridinium l-PhCH -picolinium... 

Radial-Pak p Honda pa k Cig cartridge. Butanol-methanol-acetic acid-water (4 2 1 43) containing 0.15 mM-1 -phenethyl-2-picolinium bromide [3 mL/min]. UV at 254 nm Soya bean leaves. Detection limit 1 nmol [153]... 

The reaction between the perchlorate salt of 2,3,3-trimethylindolenine and crotonaldehyde involves Michael addition (at the 2-methyl group, not the N atom) and spontaneous cyclization to give 8.8,10-trimcthyl-l ()//-pyrido l,2-a indolium perchlorate (16) in 26% overall yield. This can be considered a vinylog of a Fischer s base salt (and also a 4-picolinium salt). This salt has been condensed with aromatic aldehydes to give styryl dyes, but there is no report of reaction with salicylaldehydes.26... 

Support for the constitution XXVII was obtained from the alkylation of sempervirine, which was shown to proceed with formation of Va-alkyl derivatives (90, 91). Thus, sempervirine methochloride gave, on distillation with selenium, a base which was identified as Va-methylyobyrine (90, 92). The structure XXVII is also consistent with the high dipole moment (8D) of sempervirine (91, 93). The hydrogen atom obtained in the Zerewitinow determination is now attributed to the presence in XXVII of a virtual y-substituted picolinium system (90). 

Asymmetric hydroamination using a chiral PIGIPHOS-Ni(II) complex has also been achieved in ionic liquids, as shown in Scheme 9.38.11431 A number of different imidazolium and picolinium ionic liquids were tested and relative to THF, much higher turnover numbers (300 vs. 20) were observed in the reaction between methacrylonitrile and morpholine at comparable selectivity (64% ee vs. 69%). Moreover, the catalyst in the ionic liquid solution is less sensitive to air and moisture so that non-distilled reagents can be used. 

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