Recent advances in the chemistry of thieno[2,3-b]pyridines 1. Methods of synthesis of thieno[2,3-b]pyridines

Russian Chemical Bulletin - The recent data (2007–2018) on the synthesis of thieno[2,3-b]pyridines are summarized and systematized.     

Mass spectra of isomeric thieno [2,3-b]- and thieno[3,2-b]pyridines

The mass spectra of six isomeric thieno- and thionaphthenopyridines were studied for the first time, and the pathways of fragmentation of the molecular ions, which made it possible to isolate the peaks of the fragment ions that characterize the destruction of the pyridine and thiophene rings, were traced. It is shown that the character and type of conjugation of the heterorings can be distinguished by analyzing the mass-spectral data. The relationship between the intensity of the peak of the doubly charged molecular ion and the number of electrons in the system and the -donor character of the heteroring was illustrated by means of the literature data on the mass spectrometry of heteroaromatic systems with one heteroatom.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 758–761, June, 1982.     

Thieno [2,3 -b] pyridines and thieno [ 3,2 -b] pyridines by the method of gould-jacobs

Bis(2-, and 3-thienylammonium) hexachlorostannates were condensed with ethoxymethylene derivatives of active methylene compounds in pyridine. The resulting condensation products IVa-IVc and Va-Vc on heating under reflux in Dowtherm or diphenyl ether provided various 4-hydroxythieno[2,3-b] pyridines (Ia-Ic) and 7-hydroxythieno[3,2-b]pyridines (IIa-IIc). The compound Ic on further transformations gave yet other derivatives If-Ik.     

New method for the synthesis of substituted thieno[3,2-b]pyridines and 5H-pyrano[2,3-d]thieno[3,2-b]pyridines derived from them

A new highly selective method was developed for the synthesis of substituted thieno[3,2-b]-pyridines based on the domino reaction of monopotassium salt (rather than dipotassium one) of carbamoylcyanodithioacetic acid with ethyl 4-chloroacetoacetate. Substituted 5H-pyrano[2,3-d]-thieno[3,2-b]pyridines were synthesized based on these thieno[3,2-b]pyridines.     

A simple synthesis of thieno[2,3-b]pyrazine and thieno[2,3-b] pyridine

A facile synthesis of thieno[2,3-b]pyrazine (1) and thieno[2,3-b]pyridine (9) is reported. Furthermore, convenient preparations of a variety of synthetically useful compounds derived from these ring systems is also presented.     

Facile preparation of benzo[4,5]thieno[2,3-b]pyridines and naphtho[b-4,5]thieno[2,3-b]pyridines via the reaction of Barton esters and benzynes

Titled compounds were prepared in a one-pot synthesis by generating symmetrically substituted benzyne intermediates by the diazotization of anthranilic acids in the presence of Barton esters. Unsymmetrically substituted aryne either gave mixtures of regioisomers or failed. However, nitro and methyl derivatives of titled compounds could be obtained as single products using appropriately substituted Barton esters.     

2-Bromo-i-phenylethylidenemalononitrile in the synthesis of thieno[3,2-b]pyridines and thiazolo[4,5-b]pyridines

A novel regioselective synthesis of thieno[3, 2-blpyridines and thiazolo[4,5-blpyridines from 2-bromo-I-phenyl ethylidenemalononitrile is proposed. In the case of the thiazolo[4, 5-b]pyridines, the intermediate 5-(2, 2-dicyano-l-phenylvinyl)thiazoles were separated. Formation of the thiazolo(4,5-b]pyridines was confirmed by x-ray analysis.A. D. Zelinski Institute of Organic Synthesis, Russian Academy of Sciences, Moscow 117913. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 413–419, March, 1996. Original article submitted December 22, 1995.     

Synthesis and transformations of 3-(1H-pyrrol-1-yl)thieno[2,3-b]pyridines

Reactions of 2,5-dimethoxytetrahydrofuran with 3-aminothieno[2,3-b]pyridines afford a number of substituted 3-(1H-pyrrol-1-yl)thieno[2,3-b]pyridines. The possibility of the reaction and the yield of the product are determined by the character of a substituent in position 2 of thieno[2,3-b]pyridine. The Curtius rearrangement of 2-acylazido-3(1H-pyrrol-1-yl)thieno[2,3-b]pyridines yields 4,5-dihydropyrido[3",2":4,5]thieno[2,3-e]pyrrolo[1,2-a]pyrazin-4-ones. The molecular and crystal structures of ethyl 4-methoxymethyl-6-methyl-3-(1H-pyrrol-1-yl)thieno[2,3-b]pyridine-2-carboxylate were determined by X-ray diffraction analysis.     

Piperazine-mediated tandem synthesis of bis(thieno[2,3-b]pyridines): Versatile precursors for related fused [1,2,4]triazolo[4,3-a]pyrimidines

In this study, we discuss the utility of bis(cyanoacetamides) as versatile precursors to the piperazine-mediated synthesis of a wide spectrum of bis(thieno[2,3-b]pyridine) derivatives, linked to aliphatic spacers via thioethers. The proposed tandem protocol involved the reaction of bis(cyanoacetamides) with two equivalents of the appropriate cinnamonitriles in dioxane in the presence of six equivalents of piperazine at reflux for 4 hours. Then, two equivalents of the appropriate halogen-containing reagents were added and the reaction was heated at reflux for further 3 hours. The bis(thieno[2,3-b]pyridines) were taken as a key intermediates to new bis(4-oxopyrido[3′,2′:4,5]thieno[3,2-d]pyrimidines). The above derivatives were reacted with the appropriate hydrazonyl chloride derivatives in dioxane in the presence of triethylamine to yield the corresponding bis([1,2,4]triazoles) with a related fused pyridothienopyrimidine moiety. The new structures were elucidated by IR, NMR spectral data, as well as elemental analyses.     

The synthesis and chemical reactivity of thieno[2,3-c]- and thieno[3,2-c] pyridines

The syntheses and reactions of various thieno[2,3-c]- and thieno[3,2-c] pyridines are described. Molecular orbital calculations were performed on thieno[2,3-c]pyridine (1) in order to determine the most susceptible sites to electrophilic and nucleophilic attack. Superdelocalizability values, S_r- are reported for each position in this molecule to give relative orders of reactivity towards the two types of reactions. Electrophilic attack was found to occur experimentally at C-3 in all the thienopyridines studied. Peracid oxidation of thieno[2,3-c]- and thieno[3,2-c]pyridines produced only the N-oxide. The lack of reactivity of certain thienopyridines under Vilsmeier formylation and Friedel-Crafts acetylation conditions was related to their basicities. The dissociation constants of various thienopyridinium salts are reported.     

Synthesis of new condensed thieno[2,3-b]pyridines containing pyrimidine and imidazole rings

Two different convenient methods have been developed for the synthesis of condensed thieno[2,3-b]pyridines. The intramolecular cyclization of 3-amino-2-hydrazinocarbonyl-7,7-dimethyl-7,8-dihydo-5H-pyrano[3,4-e]-thieno[2,3-b]pyridine was carried out to give 7,7-dimethyl-2-oxo-1,2,6,7-tetrahydro-9H-pyrano[3′,4′-e]-imidazo[4″,5″∶2,3]thieno[5,4-b]pyridine, which is the first representative of a new heterocyclic system.     

Nitriles in heterocyclic synthesis: A novel synthesis of some thieno[2,3-d]pyrimidine and thieno[2,3-b]pyridine derivatives

A simple route to the synthesis of the pharmaceutically important thieno[2,3-d]pyrimidine derivatives and of thieno[2,3-b]pyridine derivatives via the use of 5-amino-3-phenylthiophene-2,4-dicarbonitrile (2) as a starting material is described. © 1996 John Wiley & Sons, Inc.     

Synthesis and structural characterization of substituted thieno[2,3-b]pyridines from o-chloroformyl-1,4-dihydropyridines

Novel 4,7-dihydrothieno[2,3-b]pyridines 10a-d have been prepared in a one step procedure from the readily available o-chloroformyl substituted 1,4-dihydropyridines 9a-d and ethyl mercaptoacetate in good yields. Semiempirical calculations reveal a favoured geometry with a boat conformation in the dihydropyridine system and a planar thieno ring. The calculated charge density values for the olefmic carbons (C5 and C6) are in agreement with the experimental push-pull effect observed in the ¹³C nmr.     

Chemistry of thienopyridines. IV. Syntheses of 5-substituted thieno[2,3-b] pyridines

Chemical transformations on 5-acetylthieno[2,3–6] pyridine produced 5-NH₂, 5-CO₂H, and 5-CH₂ CO₂H substituents. The 5-amino compound underwent facile diazotization (plus Sand-meyer reaction), Schiff's base formation, and acylation. Treatment of the derived 5-bromo compound with potassium amide in liquid ammonia gave a mixture of 4-amino (major) and 5-amino isomers. Nmr spectral data are reported for the 5-substituted thieno [2,3-b] pyridine system.     

Synthesis of substituted thieno[2,3-b]pyrroles

A relatively simple route for synthesis of substituted thieno[2,3-b]pyrroles from readily available starting material and data for structural assignment are reported.     

A concise synthesis of functionalized 2,3-dihydrofuro[3,2-b], [3,2-c], and [2,3-b]pyridines

A strategy for the efficient and rapid one-pot synthesis of 2-aryl-2,3-dihydrofuro[3,2-b], [3,2-c], and [2,3-b]pyridines from readily available o-nitropicolines and aromatic aldehydes is described. The key transformation involves reaction of o-nitropicolines with aromatic aldehydes in the presence of TBAF and Hünig's base giving rise to functionalized products having molecular complexity suitable for further manipulation.