ChemInform Abstract: An Expedient Route to 1H-Benzimidazoles and 1H-Imidazopyridines (original) (raw)
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An Expedient Route to 1H-Benzimidazoles and 1H-Imidazopyridines
Bulletin des Sociétés Chimiques Belges, 1993
ÀBSTRÀCT 1H-Benzimidazoles, LH-inidazo [ 4, 5-b]pyridines, and 1II-inidazo [ 4, 5-c]pyri.dines can be synthesized readily by reaction of unisolated N-(L-chloroalkyl)pyridinium chlorides with L,2-benzenediamines, 2,3-pyridinediamine, and 3, 4-pyridinediamine respectively.
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
Organic Letters, 2011
A base promoted cyclization of the protected N-propargylaminopyridines was shown to be an efficient method for the preparation of imidazo[1,2-a] pyridine derivatives. The reactions were carried out with a small excess of base, at room temperature or slightly above producing the heterocyclic products in moderate to good yields. The stereoelectronic properties of substituents on the pyridine ring were shown to influence the cyclization process.
Recent Developments in the Synthesis of Pyrido[1,2-a]benzimidazoles
Synthesis
Pyrido[1,2-a]benzimidazole is one of the most important azaheterocyclic compounds consisting of three fused aromatic rings. Molecules containing this core have displayed a wide range of applications in the field of medicinal chemistry. The synthesis of pyrido[1,2-a]benzimidazole and its derivatives has attracted organic chemists because of its tremendous utility in interdisciplinary branches of chemistry. In this context, this review discusses the main advances in the synthesis of pyrido[1,2-a]benzimidazoles via metal-mediated and metal-free reactions from 2000 to 2016.1 Introduction2 Synthetic Approaches to Pyrido[1,2-a]benzimidazoles2.1 Type I: Transition-Metal-Catalyzed Methods2.2 Type II: Metal-Free Approaches3 Conclusion
Efficient synthesis of imidazole and pyrimidine derivatives
Chemistry of Heterocyclic Compounds, 2020
Amidines are known reagents in some synthetic methods for obtaining heterocyclic compounds as well as they are used as suitable reagents in numerous cycloaddition processes. An example of their application is the synthesis of pyrimidines and imidazoles shown by Vidal and coauthors. 1 Also, a new efficient and convenient approach was proposed to the synthesis of pyrimidines by Cu-catalyzed and 4-HO-TEMPO-mediated [3+3] annulation of commercially available amidines with saturated ketones. 2 On the other hand, diazaheterocyclic compounds are interesting from various scientific aspects 3 and have a significant potential as modern functional materials, 4 as well as they could be considered as objects which have a significant interest from the point of view of biological activity. 5 The aim of the work was to develop on the basis of known procedures 6 a method for the synthesis of N,N'-unsubstituted α-aminoamidines and ways for their further modification to synthesize new promising imidazole-and pyrimidine-containing compounds. We proposed and optimized a convenient and affordable pathway for the synthesis of previously undescribed α-aminoamidines 4a-e starting from N-protected amino-nitriles 1a-e, which can be easily obtained by described methods (Scheme 1). 7,8 The key stage of the approach is a procedure of hydrogenation of O-acetyl-substituted amino-oximes 3a-e in the presence of palladium catalyst. 9,10 It should be noted, that our attempts to perform direct reduction of aminooximes 2a-e to aminoamidines 4a-e were unsuccessful, though such transformations for amidines had been described in literature earlier. 11-16 Therefore, we carried out preliminary O-acylation of compounds 2a-e by acetic anhydride. A convenient and affordable synthetic pathway for obtaining new α-aminoamidines starting from aminonitriles is proposed. The α-aminoamidines obtained can be applied as substrates for further transformations and synthesis of imidazole-and pyrimidine-containing building blocks.
Molecules (Basel, Switzerland), 2016
1-alkyl aryl-5-amino-4-(cyanoformimidoyl)imidazoles 4 were reacted with malononitrile and 2-amino-1,1,3-propenetricarbonitrile under mild experimental conditions, which led to 5-amino-3-(substituted benzyl)-6,7-dicyano-3H-imidazo[4,5-b]pyridines 5 and 6,8-diamino-3-(4-substituted benzyl)-3H-imidazo[4,5-b]-1,8-naphthyridine-7,9-dicarbonitrile 6, respectively, when the reaction was carried out in the absence of a base, or to 5,7-diamino-3-(4-alkyl aryl)-3H-imidazo[4,5-b]pyridine-6-carbonitrile 8, and 6,8,9-triamino-3-(4-substitutedbenzyl)-3H-imidazo[4,5-b]-1,8-naphthyridine-7-carbonitrile 10 in the presence of 1,8-diazabicyclo(5.4.0)undec-7-ene (DBU). Both reactions evolved from an adduct formed by nucleophilic attack of the malononitrile anion or 2-amino-1,1,3-propenetricarbonitrile anion to the carbon of the cyanoformimidoyl substituent. In the case of the malononitrile anion, a 5-amino-1-alkyl aryl-4-(1-amino-2,2-dicyanovinyl)imidazole 7 was isolated when this reaction was carried ...
2007
SYNTHESIS 2007, No. 17, pp 2667–2673xx.xx.2007 Advanced online publication: 08.08.2007 DOI: 10.1055/s-2007-983852; Art ID: P02607SS © Georg Thieme Verlag Stuttgart · New York Abstract: A new method for the synthesis of substituted imidazo[1,5-a]pyridines (2-azaindolizines) starting from carboxylic acid and 2-methylaminopyridine is described. The reaction of the obtained N-2-pyridylmethylamides with Lawesson’s reagent generated the target imidazopyridines, along with the corresponding thioamide intermediates. After a simple filtration on alumina, addition of mercury(II) acetate allowed for total conversion of the thioamides into the imidazopyridines. The reaction conditions, as well as the influence of the substituent in position 3 of the imidazopyridine ring were explored. We also demonstrated that this heterocyclization was racemization free in the presence of a chiral carbon in position a to the heterocycle.