Alkylpyridine

The effect of alkyl groups in the 5-position on the reactivity of the thiazole nitrogen is analogous to that found for 3-alkylpyridines, in other words, a simple inductive effect. In passing from the unsubstituted heterocycle to the methyl derivative, the rate constant doubles a further increase in substitution produces a much less pronounced variation. 

Table III-55 shows the verification of the Taft equation. The result is analogous to that obtained for 3-alkylpyridines.

A solution of sodamicle in liquid ammonia (essentially the amide NHj ion) is a very powerful alkylation catalyst, enabling condensations to be carried out with ease and in good yield which are otherwise either impossible or pro ceed with difficulty and are accompanied by considerable by-products. Thus 3-alkylpyridines, otherwise inaccessible, are easily prepared from 3-picoline (see 3- -amylpyridine in Section V,20). Also benzyl cyanide (I) and cycZohexyl bromide give a- r/ohexylphenylacetonitrile (II) ... 

Alkylpyridines supposedly lie also along another biosynthetic route, affording pofymeric pyridinium compounds in marine haliclonid sponges the Indo-Pacific Callyspongia fibrosa (Davies-Coleman 1993), the Caribbean Amphimedon compressa (Albrizio 1995), and the Mediterranean Reniera sarai (Sep5i6 1997). 

Mar. ALKAL. 3-alkylpyridine, azirine, azacyclodecanes, p-carboline, C, or C22 bromopyrrole, guanidine, halotyrosine, (bis)imidazole, (bis)indole, imidazoiyi pyrroloazBpine, indolizidine, pept. alkal., pyridazine. high high... 

Alkylpyridines are aminated preferentially at the 2-position, but reaction is slower than in the parent system. Quinoline is difficult to aminate and only a low yield of 2-aminoquinoline (32%) is obtained from reaction with sodamide in toluene. When dimethylaniline is employed as solvent, 2-amino-3,4-dihydroquinoline (24%) becomes the major product, and the yield of 2-aminoquinoline drops to 7%. The best yields of 2-aminoquinoline (53-69%) have been obtained by using barium or potassium amide in liquid ammonia. Use of the potassium salt also produces a 10% yield of the 4-amino isomer. The... 

In a reactivity study conducted by competitive methods, the influence of 3-alkyl groups (Me and Et) has been found to be rather peculiar.135 3-Alkylpyridines are attacked at the adjacent 2-position more easily than pyridine itself in spite of the weak adverse electronic effect of the substituent. However, at the 6-position the attack occurs more slowly, as expected. Of the several possible reasons for this behavior, probably the most likely is the establishment of a weak attractive interaction between the a carbon of the 3-alkyl group and phenyllithium, which would favor orientation for attack at the 2- rather than the 6-position and overcome the small electronic effect of the group. 

The above reactions have been illustrated for 2- and 4-alkylpyridines. They generally fail if no heteroatom is a or 7, as in 3-alkylpyridines and 5-alkylpyrimidines. a- and [3-Alkyl groups in pyridine A-oxides are somewhat more reactive than those on the corresponding pyridines. In addition to the reactions already mentioned, 2-picoline 1-oxide undergoes Claisen condensation with ethyl oxalate to yield the pyruvic ester (630) (for the conversion of alkyl substituents in A-oxides into CH,OAc groups see Section 3.2.3.12.5.iv). 

Reaction of dihydropyridine 378 with aldehydes like 379 involves C(3) atom [322], but the treatment is more complicated and can lead to further transformations resulting in the formation of 3-alkylpyridines 380 (Scheme 3.100). 

Spinella, A., Alvarez, L. A., Passeggio, A., and Cimino, G., New 3-alkylpyridines from three Cephalaspidean molluscs structure, ecological role and taxonomic relevance, Tetrahedron, 49, 1307, 1993. 

There is no doubt that in these. reactions the nitrogen atom of the pyridine ring is complexed with either the lithium alkyl or aryl or with the lithium bromide which is usually present in many preparations of organolithium compounds. It has been established that, either in the presence of an excess of lithium bromide or in the total absence of this salt, phenyllithium still gives the same ortho .para ratio on reaction with 3-picoline.229 To account for the predominant formation of the 2,3-isomer in the reaction of CH3Li with 3-alkylpyridines, it was suggested261 that the transition states for these reactions were similar... 

Selenium dioxide oxidizes CH3 to CHO (662 663) and this differentiates 2- and 4-methyls from 3-methyl, e.g., Scheme 85 <2003SC475>. Conversion of 2- and 3-alkylpyridines into chiral hydroxyalkyl derivatives can be achieved with the enzyme toluene dioxygenase from the mutant soil bacterium Pseudomonas putida in high ee <2002TA2201>. 

Alkylpyridines. The reaction between ethylene and 3-alkylpyridines in the presence of alkali metal is much more complicated than similar reactions made with the corresponding 2 and 4 isomers (29). The two primary products from the reaction of 3 -ethylpyridine with ethylene in the presence of either sodium or potassium are 3-sec-butylpyridine and cyclic compound M. Further ethylation occurs with a longer reaction time to form 29. 

AKYLPYRIDINIUM AND 3-ALKYLPYRIDINE COMPOUNDS FROM MARINE SPONGES, THEIR SYNTHESIS, BIOLOGICAL ACTIVITIES AND POTENTIAL USE... 

We present an overview of the structures for 3-alkylpyridine and 3-alkylpyridinium compounds that have been isolated, taking into account the structural characterization of alkylpyridinium compounds and discussing the central role played by mass spectrometry. Concerning their synthesis, both the natural pathways and organic synthesis of pyridinium alkaloids are reviewed. Synthetic aspects of 3-alkylpyridines have been taken into account only where relevant for structural modifications or for the assignment of absolute configurations. Finally, biological activities of both 3-alkylpyridine and 3-alkylpyridinium compounds and the potential use of the latter are discussed. 

ALKYLPYRIDINE AND ALKYLPYRIDINIUM COMPOUNDS FROM MARINE ORGANISMS... 

Later, Baldwin and co-workers reported an efficient synthesis of the whole series of cyclostellettamines A-F [44]. The appropriate monomeric 3-alkylpyridine was prepared, as illustrated in Fig. (28), from 3-methylpyridine (81), or from 3-pyridin-3-ylpropanal (82) when tridecan-1,13-diol was unavailable as a commercial reagent. 

The procedure can also be applied in the case of substrates 87 and 88 bearing different chains. This is the case for the synthesis of the asymmetrical bis-pyridinium macrocycle, a precursor of haliclamine A [50]. As illustrated in Fig. (34), the 3-alkylpyridine derivatives 93 and 94, obtained by the commercially available thiophene 92, lead to the dimeric macrocycle via the Zincke procedure, which affords obtaining haliclamine A (49) by reduction. 

Table I. Cytotoxic activity of 3-alkylpyridine and 3-alkylpyridinium compounds from marine sponges on...

In the absence of an added solvent, 3-alkylpyridines, 4-alkyl-pyridines, and 3,4-dialkylpyridines all gave yields of substituted 2,2 -bipyridines that were up to three times greater than that of 2,2 -bipyridine from pyridine under similar conditions. With 3-ethyl-4-methylpyridine a marked improvement in yield was observed when the reaction was carried out at about 150°C in a vacuum, rather than at the atmospheric boiling point (195°C) of this base. This effect has also been observed with some other bases but the amount of 3,3, 5,5 -tetramethyl-2,2 -bipyridine from 3,5-lutidine could not be increased in this way, and this pyridine was as unreactive as the 2-substituted pyridines. This finding is undoubtedly related to the reluctance of 3-substituted pyridines to form 3,3 -disubstituted 2,2 -bipyridines. 

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