Displacement picoline

The alkyne ligand is not displaced by CO or ethene but is substituted by stronger (T-donor ligands like pyridine and 4-picoline, which give the paramagnetic... 

A compound that includes an aminopyrimidine ring as well as the quaternary salt present in thiamine shows preferential inhibition of absorption of that co-factor by coccidia parasites over uptake by vertebrates. The compound is thus used in poultry where coccidiosis is an economically important disease. Condensation of ethoxymethylenemalononitrile (42-1) with the amidine (42-2) leads to the aminopyrimidine (42-4), probably via the intermediate addition-elimination intermediate (42-3). The nitrile group is then reduced to the methylamino derivative (42-5) by means of hthium aluminum hydride. Exhaustive methylation, for example by reaction with formaldehyde and formic acid, followed by methyl iodide leads to the quaternary methiodide (42-6). The quaternary salt is then displaced by bromine, and the resulting benzyhc-like cylic halide (42-7) is displaced by 2-picoline (42-8). There is thus obtained amprolium (42-9) [43]. 

The reaction between heteroaromatic iV-oxides and 2-chloro, 5-dihydroimidazole 955 results in a formal ureida-tion of the heteroaryls. This reaction was extended to 2- and 4-picoline iV-oxides for the synthesis of 956 and 957, respectively (Scheme 232) <2002JHC911>. The 2-bromine of nitronyl nitroxide 958 is easily displaced with sodium azolides to give spin-labeled azoles (imidazole, pyrazole, triazole) 959 which are prone to hydrolysis to hydroxamide acid anion 960 <2004T99>. 

Displacement of the chloro substituent from pyrazines by the cyano group has not been satisfactorily accomplished (866), but many cyanopyrazines have been prepared from the bromo analogues. Karmas and Spoerri (866) prepared 11 cyanopyrazines with mono-, di-, or trialkyl or phenyl substituents from the corresponding bromo compounds and cuprous cyanide in refluxing dry 4-picoline, but the procedure was not suitable for the preparation of 2-cyanopyrazine (866). It was prepared in 29% yield when the reaction was performed in pyridine (866). Another preparation of 2-cyano-3-phenylpyrazine from the bromo analogue has also been reported (1024). 

Since the forward reaction in (29) is exothermic, the equilibrium is displaced to the left by increase in temperature this factor accounts in part for the anomalous temperature coefficient of reaction rate mentioned above. The apparent catalysis by propagating base is also explicable as acid catalysis since the carbamic acid is stoichiometrically derived from the base by reaction (29). That true base catalysis is not operative has been shown by the observation that addition of tertiary bases does not affect the reaction rate [17]. Further, the polymerization is catalysed by other weak acids such as hydrocinnamic [17] and a-picolinic acids [10, 17], which, if present in sufficient concentration under conditions of low CO2 pressure, reduce the order in initiating base to unity. Thus, under such conditions, with hydrocinnamic acid (HX) as catalyst the simple kinetic form (30) is achieved. 

A similar chelated TPP compound 60 was used by Walker to study the effect of axial ligand plane orientation on the H-NMR shifts of the pyrrole protons in iron(III) (TPP)bis(imidazole) cotnplexes In this case the tail was made shorter to study the effect of axial ligand bond strain. In addition. Walker and Benson have used mono-(o-aminophenyl)triphenylporphyrin (57) to prepare a series of derivatives 6la-e containing a pyridine ligand bound to a zinc TPP . H-NMR and visible spectroscopy were used to study the displacement of the 3-pyridyi ligand by free 3-picoline (Scheme 23),... 

The condensation of piperazine or other amines is usually accomplished without solvent or in pyridine, diisopropylethylamine, iV-methylpyrrolidinone, or P-picoline. The displacement of the chlorine atom proceeds quite regio-selectively and almost only 3 is obtained with some minor amounts of material with fluorine substitution. The analogs in the naphthyridone series have been synthetized by a different process, the introduction of the fluorine atom was the main synthetic difficulty to solve. An early synthesis of enoxacin is given in Fig. 4 [5]. 

A first-stage product resulting from the nucleophilic displacement of flie Cl atom by the pyridine N atom of a-picoline under milder reaction conditions is isolated and characterized and is then required for the formation of a spiro-compound or its... 

The formation of a rearrangement product can be represented by Scheme 6.51. According to this scheme, the initial step involves the nucleophilic displacement of the Cl atom by the pyridine N atom, which is followed by a cascade transformation. The latter involves (a) dehydrochlorination with the abstraction of a methyl H atom of a-picohne, (b) intramolecular nucleophilic addition of the methyUdene C atom of the a-picoline fragment to the azomethine C atom of the quinoxaUne system... 

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