Fast and efficient direct conversion of 2-aminopyridine into 2, 3-disubstituted imidazo [1, 2-a] pyridines (original) (raw)
Related papers
2014
Various sulfonic and carboxylic acids were tested as catalyst in a direct acid catalyzed conversion of 2aminopyridines and acetophenones into 2,3-disubstituted imidazo[1,2-a]pyridines in order to improve the reaction yield. The most effective catalyst, isoquinoline-5-sulfonic acid, was applied in the reaction between substituted aminopyridines and acetophenones. The efficiency of the catalysts and their influence on the products distribution is discussed. Several chiral acids were also used but no stereoselectivity was induced. NMR study shows existence of two different species in the solid state, differentiation between them was not possible based on the available experimental and theoretical considerations.
ACS Omega
A highly efficient, clean, and simple procedure for the synthesis of a privilege imidazo[4,5-b]pyridine scaffold from 2-chloro-3-nitropyridine in combination with environmentally benign H 2 O-IPA as a green solvent is presented. The scope of the novel method has been demonstrated through the tandem sequence of S N Ar reaction with substituted primary amines followed by the in situ nitro group reduction and subsequent heteroannulation with substituted aromatic aldehydes to obtain functionalized imidazo[4,5-b]pyridines with only one chromatographic purification step. The synthesis pathway appears to be green, simple, and superior compared with other already reported procedures, with the high abundance of reagents and great ability in expanding the structural diversity.
A revised approach to the synthesis of 3-acyl imidazo[1,2-a] pyridines
Heterocyclic Communications, 2010
3-Acyl imidazo[l,2-a]pyridines with no substituent at position 2 were obtained in moderate to good yields in an improved version of the Tisler protocol for the synthesis of imidazo[l,2-x]azines. It was found that yields are significantly improved if the reaction is carried out in the presence of DMF or in some cases in the absence of a solvent. INTRODUCTION The fused heterocyclic system imidazo[l,2-a]pyridine is an important pharmacophore, as is demonstrated by the broad variety of pharmacological activities shown by its derivatives.' The most common approach to the synthesis of the imidazo[l,2-o]pyridine ring is based on the condensation reaction of 2-aminopyridines with a-halocarbonyl compounds. 2 This methodology allows the direct construction of 2 or 2,3-substituted imidazo[l,2-a]pyridines, but is not usefiil for the synthesis of 3-acyl imidazo[l,2-a]pyridines with no substituent at position 2. The interesting aspect of 3-aroyl imidazo[l,2-a]pyridines is their potential biological activity. Thus, derivatives of 2-amino-3-aroyl imidazo [l,2-a]pyridines have been evaluated as antiviral agents. 3 A useful method of synthesis of 3-acyl imidazo[l,2-a]azines is the intramolecular cyclization of alkylated iV-heteroaryl formamidines, described by Tisler. 4,5 Direct thermal regiospecific acylation of 7-methyl imidazo[l,2-a]pyridine has also been reported. 6 Since our research program required 3-aroyl imidazo[l,2-a]pyridines unsubstituted at position 2 to carry out several studies, the Tisler method was the best option to synthesize them. However, in the Tisler protocol the related derivative 2-methyl-3-benzoylimidazo[l,2-a]pyridine 2 was obtained in only 16% yield via condensation of formamidine 1, with the corresponding α-bromoketone. The results of an adaptation of such methodology to the synthesis of 3-acyl imidazo[l,2-a]pyridines unsubstituted at position 2 are presented herein. RESULTS AND DISCUSSION The study began with a multicomponent approach to the 3-acyl imidazo[l ,2-a]pyridine heterocyclic system, employing 2-aminopyridine, 2-bromoacetophenone and formaldehyde. However, from this experiment only 2-phenylimidazo[l,2.a]pyridine was obtained. Then DMFDMA, a well known one carbon synthon useful in the synthesis of heterocycles, 7 was used in place of formaldehyde. This attempt was also unsuccessful, giving only traces of 3-(4'-chlorobenzoyl imidazo[l,2-a]pyridine. Therefore, it was decided to directly treat the jV'-pyridylformamidine 3
One-pot synthesis of substituted imino-and imidazopyridines under catalyst-free conditions
Substituted imino-and imidazopyridine derivatives were synthesized via a new one-pot, three-component reaction between benzylidenemalononitriles, malononitrile and amines under catalyst-free conditions at room temperature. When ethylenediamine was used as the amine component of the reaction, dihydro-and tetrahydroimidazopyridines were selectively obtained in good to high yields. On the other hand, the use of benzylamine led to the formation of 2imino-1,2-dihydropyridine products. The reactions were found to tolerate the presence of electron-donating and withdrawing substituents on the benzylidenemalononitrile reactants. Products of these reactions are crystalline and can be isolated by a simple procedure at room temperature in good yields and with high purity.
Recent Progress in Metal-Free Direct Synthesis of Imidazo[1,2-a]pyridines
ACS Omega
This Mini-Review highlights the most effective protocols for metal-free direct synthesis of imidazo[1,2-a]pyridines, crucial target products and key intermediates, developed in the past decade. The emphases is given on the ecological impact of the methods and on the mechanistic aspects as well. The procedures efficiently applied in the preparation of important drugs and promising drug candidates are also underlined.