THE PREPARATION OF 2-ALKYL AND 2-ARYL PYRIDINES AND QUINOLINES BY THE GRIGNARD REACTION¹ (PRELIMINARY)

Abstract

CH CH\Nŝ o-there is present the same-CH=N-group that occurs in the Schiff bases and is characteristic of aldehydes of the ammonia system. Furthermore, pyridine and all substances containing a pyridine nucleus also partake of the nature of acetals, since one valence of the nitrogen is attached to one side of a closed ring. Hence pyridine, quinoline and isoquinolme can be regarded in a formal sénse as cyclic ammono aldehyde acetals.4 Nevertheless, the aldehydic properties one might expect these substances to show are subordinated because of the remarkable stability of the sixmembered ring with alternate double and single bonds.5 Thus, pyridine is not appreciably oxidized by hot concentrated sulfuric or nitric acid. Quinoline may be oxidized to quinolinic acid by potassium permanganate in alkaline solution with the destruction of the benzene ring.However, if the stability of the pyridine ring of quinoline be diminished

Properties and Reactions of Thiazole

“…When the low-temperature adduct is heated in an autoclave at 90 to 170°C for 3 to 6 hr, it does not rearrange to 2-ethylthiazole (12) as is the case in the pyridine series (436). Similarly, thiazole reacts at -60°C with phenyllithium affording thiazol-2-yllithium (156) (13,437).…”

Alkylation of Pyridines at Their 4‐Positions with Styrenes plus Yttrium Reagent or Benzyl Grignard Reagents

“…For example, nucleophilic addition of organometallic reagents to pyridines takes place mostly at their 2-or 4-positions, among which the former appears more feasible, but the selectivity is often difficult to control. [1][2][3][4][5] A similar issue is also found in the alkylation of pyridines through CÀH bond activation, in which the reaction preferentially occurs at the 2-position of pyridines, [11,12] likely facilitated by the initial interaction between the metal reagents and the pyridine nitrogen. Thus, the highly regioselective substitution of pyridines at the 4-position has been less frequently encountered [4,5,12] and still calls for newer, simpler, or more dependable methods using inexpensive reagents.…”

“…As nucleophilic addition at the 2-position of pyridines is more common than that at 4-position, [1][2][3][4][5] the exclusive addition of benzylmetal species at the 4-position as shown in Scheme 2 should be synthetically quite useful.…”

“…For the benzylmetal species, we chose the convenient ones, Grignard reagents, [1][2][3][4][5] and initiated the investigation, results of which are summarized in Table 3. When 2-ethylpyridine (1 a) (1 equiv) and 1-[p-(tert-butyl)phenyl]ethylmagnesium chloride (12 a) (2 equiv) were heated at reflux in THF for 18 h (Table 3, entry 3), the desired 4-alkylated pyridine 4 h was isolated in 74 % yield.…”

“…[1] Their synthetic methods rely on traditional reactions include nucleophilic [1][2][3][4][5][6] or radical [1,7] additions to pyridines, metalation of pyridines, [1,8] and multicomponent coupling reactions from acyclic starting materials. [1,9] In addition to these, new syntheses through CÀH bond activation of pyridines have recently appeared.…”