Synthesis and molecular structure of 3,7-dimethyl-2-[N-(4-methylpyridyl-2)-4-hydroxy-3-methyl-5-oxopyrrolen-3-yl-2]imidazo[1,2-a]pyridine

Abstract

Keywords: 1-amino-4-methylpyridine, α-chlorooxirane, α-hydroxy acid, imidazo[1,2-a]pyridine, heterocyclic carbaldehyde.The presence in α-chloroepoxides of type 1 of a potential aldehyde group -the acetal fragmentpredetermines the high reactivity of these electrophilic reagents. We have shown that acetal-containing α-chlorooxiranes [1] are suitable starting reagents for the synthesis of five-and six-membered heterocyclic carbaldehydes and their derivatives [2][3][4].To widen the synthetic potential of these substrates and to obtain polyheterocycles we have studied the condensation of α-chlorooxirane 1 with the aminopyridine 2. The reaction occurred in boiling isopropanol over 3 h to give the heterocycle 9.The very unexpected formation of compound 9, the structure of which was proved by 1 H NMR and X-ray crystallography, may occur as shown in the scheme (r.p. 1900).Heterocyclization occurs in the first step to form the acetal 3 which is easily converted into the carbaldehyde 4 in the acid medium. An unusual condensation of the polyaminal 5, formed by reaction of the aldehyde 4 with a second molecule of aminopyridine 2, with the product of the rearrangement of α-chlorooxirane -the α-chloro ketone 6 -then occurs, accompanied by the formation of a new carbon-carbon bond. In previous investigations we have shown that heterosubstituted α-chloroacetals in acid media underwent redox processes which led to the synthesis of α-hydroxy acids [5]. Evidently the intermediate α-keto acetal 7 was converted similarly to the hydroxy acid 8. The latter was transformed into the final product 9 by intramolecular condensation. __________________________________________________________________________________________

Tetrel, Chalcogen, and Charge-Assisted Hydrogen Bonds in 2-((2-Carboxy-1-(substituted)-2-hydroxyethyl)thio) Pyridin-1-ium Chlorides

“…In the 1 H NMR spectra of 5-8, the two protons at asymmetric centers (SCH and CНOH) display two doublets at δ 4.46 and 5.51 (for 5), 4.45 and 5.52 (for 6), 4.42 and 5.55 (for 7) and 4. 26…”

“…Reaction of 2-chloro-2-(diethoxy-methyl)-3-substituted-oxirane or 1-chloro-1-(substituted)-3,3diethoxypropan-2-one, which proved to be convenient reagents in the synthesis of interesting heterocyclic systems [25][26][27][28], with pyridine-2-thiol in EtOH at 25 • C yields 3-(diethoxymethyl)-3hydroxy-2-substituted-2,3-dihydro-thiazolo[3,2-a]pyridin-4-ium chlorides (1)(2)(3)(4), which subsequently, in MeCN at 85 • C, transforms into ring-opening products, 2-((2-carboxy-1-(substituted)-2hydroxyethyl)thio)pyridin-1-ium chlorides (5)(6)(7)(8), having tetrel, chalcogen, and charge-assisted hydrogen bonds (Figures 1-4). Additionally, the use of the dihalogen functionalized substrate 2-chloro-3-(4-chlorophenyl)-2-(diethoxymethyl) oxirane or 1-chloro-1-(4-chloro-phenyl)-3,3-diethoxypropan-2one leads to halogen bonding in the reaction product 6 ( Figure 5).…”

“…In the 1 H NMR spectra of 5-8, the two protons at asymmetric centers (SCH and CHOH) display two doublets at δ 4.46 and 5.51 (for 5), 4.45 and 5.52 (for 6), 4.42 and 5.55 (for 7) and 4. 26 These compounds may stabilize as synor anti-isomers, depending on the nature of the involved intermolecular noncovalent interactions (Figures 2-5). For example, 5 is stabilized as a syn-isomer whereas 6 is stabilized as an anti-isomer in the solid state.…”

“…Due to the strength and directionality of the CAHB, this type of noncovalent interaction has an impact on the synthesis of coordination compounds [9], crystal engineering [20][21][22][23], etc. In most cases, due to the additional electrostatic interactions involved, CAHBs are stronger in comparison to normal hydrogen bonds.On the other hand, α-hydroxy carboxylic acids are versatile and powerful intermediates for the synthesis of various chiral compounds with unique properties [24][25][26][27]. Furthermore, the functionalization of α-hydroxy carboxylic acids with 2-tiopyridine (expected chalcogen bond donor) moiety can increase their bioactivity, donor sites towards coordination, etc.Hence, on the basis of the above considerations, in this work we synthesized 2-tiopyridine functionalized α-hydroxy carboxylic acids (e.g., 2-((2-carboxy-2-hydroxy-1-arylethyl)thio) pyridin-1-ium chlorides (Scheme 1), having tetrel, chalcogen, and charge-assisted hydrogen bonds.…”

“…On the other hand, α-hydroxy carboxylic acids are versatile and powerful intermediates for the synthesis of various chiral compounds with unique properties [24][25][26][27]. Furthermore, the functionalization of α-hydroxy carboxylic acids with 2-tiopyridine (expected chalcogen bond donor) moiety can increase their bioactivity, donor sites towards coordination, etc.…”