Facile One‐pot,Three‐component Synthesis of Novel Bis‐heterocycles Incorporating 5H‐chromeno[2,3‐b]pyridine‐3‐carbonitrile Derivatives

Novel bis‐chromeno[2,3‐b ]pyridine derivatives were synthesized with good yields by a clean and efficient methodologies involving one‐pot three‐component synthesis of bis‐aldehydes, malononitrile dimer, and dimedone in the presence of piperidine as a catalyst in EtOH. Depending on the length and position of the spacer in the bis‐aldehyde derivatives 1 , the reactions proceeded to give either the bis(2,4‐diamino‐tetrahydro‐5H‐chromeno[2,3‐b ]pyridine‐3‐carbonitriles) 4 or bis(4‐amino‐2,6‐dioxo‐hexahydro‐2H‐chromeno[2,3‐b ]pyridine‐3‐carbonitriles) 5 . All of the new compounds have been characterized by spectral data.     

Synthesis of regioisomeric 2,5‐bis‐substituted‐aza‐benzothiopyranoindazoles

The synthesis of 6‐chloro‐9‐nitro‐benzothiopyranopyridin‐5‐ones 2a, 2b and 2c has been accomplished. Chemotype 2d could not be prepared since attempts to cyclize 3‐(2‐nitro‐5‐chlorophenoxy)pyridine‐2‐carboxylic acid ( 1d ) led to the decarboxylation product 3‐(2‐nitro‐5‐chlorothiophenoxy) pyridine ( 40 ). Analogues 2a, 2b or 2c on treatment with the respectively substituted hydrazine led to the 2‐(substituted)‐5‐nitro 7, 8‐ or 9‐aza substituted chemotypes 3a‐7a, 8b , and 9c‐13c . The reduction of the nitro groups of these substrates was effected by treatment with hydrogen gas (palladium catalyst) or by stannous chloride to yield the 5‐amino chemotypes 15a‐18a, 20b and 21c‐24c , respectively. The conversion of these derivatives to the 2,5‐bis (alkylamino)‐7‐, 8‐ and 9‐aza benzothiopyranoindazoles listed in Table 3 was accomplished by direct alkylations, acylations, followed by reduction of the amido group with Red‐Al or lithium aluminum hydride, or by reductive alkylations in the presence of sodium cyanoborohydride. The removal of the protective BOC‐group was effected by treatment of the appropriate substrates with anhydrous hydrogen chloride to afford the respective hydrochloride salts listed in Table 4.     

Hetarenium salts from pentafluoropyridine. Syntheses,spectroscopic properties,and applications

Reaction of pentafluoropyridine with nucleophilic heteroaromatics such as 4‐(dimethylamino)pyridine, 4‐(pyrrolidin‐1‐yl)pyridine, 4‐(morpholin‐4‐yl)pyridine, 4‐aminopyridine, and 3,4‐diaminopyridine resulted in the formation of 4‐hetarenium substituted tetrafluoropyridines. The 4‐(dimethylamino)‐pyridinium derivative underwent substitution reactions with isopropanolate, isopropanethiolate, and benzylthiolate to F²,F³,O⁴,F⁵,F⁶‐ and O²,F³,O⁴,F⁵,F⁶‐pentasubstituted pyridines as well as their sulfur analogs. N‐Propylamine, isopropylamine, and piperidine formed 4‐amino‐N²,F³,F⁵,F⁶‐pentasubstituted pyridines in the presence of sodium amide as base, whereas morpholine gave the 4‐amino‐2,6‐bis‐morpholino‐substituted 3,5‐difluoropyridine. ¹⁹F, ¹⁵N, ¹³C, and ¹H nmr spectrocopy was performed to elucidate the structures of the substitution products.     

Synthesis of New Substituted 4-Amino-3,5-dinitropyridine Derivatives

Facile synthetic routes for the preparation of some new 4-amino-3,5-dinitropyridine derivatives have been revealed. Nitration of 2-chloropyridin-4-amine （1） as a starting material, in an unexpected one-step reaction, to give dinitrated derivatives, followed by nucleophilic substitution reactions with sodium azide, potassium fluoride, ammonia, methylamine, and 4-nitroimidazol, respectively, gave substituted 4-amino-3,5-dinitropyridine derivatives. Meanwhile, its azide derivative underwent a ring closure conversion into 7-amino-6-nitro-[1,2,5]oxadiazolo[3,4-b]- pyridine-1-oxide. It is of significance that all of the nucleophilic substitution reactions were carried out under mild conditions.     

Palladium‐Catalyzed Amination of 3,5‐Dihalopyridines – a Convenient Route to New Polyazamacrocycles

Pd‐Catalyzed amination of 3,5‐dibromo‐ and 3,5‐dichloropyridine ( 1a and 1b , resp.) with linear polyamines 2 leads to the formation of a new family of pyridine‐containing macrocycles 3 with an ‘exo’‐oriented pyridine N‐atom (Schemes 1 and 2). The dependence of the macrocycle yield on the nature of the halogen atom, the length of the polyamine chain and C/N atom ratio, and the composition of the catalytic system is studied. The synthesis of mono‐ and bis(5‐halopyridin‐3‐yl)‐substituted polyamines 4, 5, 8, 9 , and of 3,5‐bis(polyamino)‐substituted pyridines 6 is described (Schemes 3 and 4), and the use of these compounds as intermediates on the way to the macrocycles 7, 16 , and 18 with larger cavity (‘cyclodimers’ and ‘cyclotrimers’) is demonstrated (Schemes 5–10).     

Synthesis of Indeno[1,2‐d]pyrimidin‐5‐Ones and Their Fluorescence in Solid State

New fluorescent compounds, 2‐substituted indeno[1,2‐d]pyrimidin‐5‐ones ( 3a , 3b , 3c , 3d ) were synthesized in good yield by the reaction of 2‐[bis(methylsulfanyl)methylene]indan‐1,3‐dione ( 1 ) with the respective amidine derivatives [guanidine carbonate ( 2a ), acetamidine hydrochloride ( 2b ), S‐methylisothiourea sulfate ( 2c ), and S‐benzylisothiourea sulfate ( 2d )]. 4‐Substituted amino‐2‐aminoindeno[1,2‐d]pyrimidin‐5‐ones ( 7b , 7c , 7d ) were synthesized by a one‐pot reaction of 1 , 2a and the respective amine compounds ( 4b , 4c , 4d ) in pyridine. These fused pyrimidine derivatives showed fluorescence in the solid state.     

Synthesis of novel substituted pyridine derivatives from 3,5‐diacetyl‐2,6‐dimethylpyridine

A series of novel (1‐acetyl‐5‐aryl‐4,5‐dihydro)‐1H‐pyrazole substituted pyridine derivatives and poly substituted [2,3′‐bipyridine]‐5‐carbonitrile derivatives were synthesized from 3,5‐diacetyl‐2,6‐dimethylpyridine. The structures of two typical 3,5‐bis[1‐acetyl‐5‐(4‐chlorophenyl)‐4,5‐dihydro‐1H‐pyrazol‐3‐yl]‐2,6‐dimethylpyridines [ 3b(1) and 3b(2) ] were confirmed by X‐ray diffraction analysis. © 2009 Wiley Periodicals, Inc. Heteroatom Chem 20:123–130, 2009; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20522     

Survey Reactivity of Some Substituted Quinazolinones with Pentafluoro(chloro)pyridine

A new series of 4‐hetroaryl substituted quinazolines were designed and synthesized by the reaction of pentafluoro(chloro)pyridine and 2‐substituted quinazolinone. The aromatic nucleophilic substitution of pentafluoro(chloro)pyridine with quinazolinone occurs at the 4‐position of pyridine ring by the oxygen site (O‐centered nucleophile) of quinazolinone. The structures of all the compounds were confirmed by IR, ¹H NMR, ¹⁹F NMR, and ¹³C NMR spectroscopy as well as elemental analysis.     

18‐Crown‐6 Catalyzed Microwave‐mediated Synthesis of Symmetric Bis‐Heterocyclic Compounds under Solvent‐free Condition

An efficient, solvent‐free and 18‐crown‐6 catalyzed method for the synthesis of N‐alkyl‐4‐(4‐(5‐(2‐(alkyl‐amino)thiazol‐4‐yl)pyridin‐3‐yl)phenyl)thiazol‐2‐amine, N‐alkyl‐4‐(5‐(2‐alkyamino)thiazol‐4‐yl)pyridine‐3‐yl)thiazol‐2‐amine, and 4,4′‐bis‐{2‐[amino]‐4‐thiazolyl}biphenyl bis‐heterocyclic derivatives via microwave accelerated cyclization is presented.     

Nitropyridines,their synthesis and reactions

Reaction of pyridine and substituted pyridines with N₂O₅ in an organic solvent gives the N‐nitropyridinium ion. When this is reacted with SO₂/HSO₃‐ in water, 3‐nitropyridine is obtained (77 % yield). With substituted pyridines the method gives good yields for 4‐substituted and moderate yields for 3‐substituted pyridines. The reaction mechanism is not an electrophilic aromatic substitution but one in which the nitro group migrates from the 1‐position to the 3‐position by a [1,5] sigmatropic shift. From 3‐nitropyridine, 5‐nitropyridine‐2‐sulfonic acid is formed in a two step reaction. From this, a series of 2‐substituted‐5‐nitropyridines has been synthesized. 3‐Nitropyridine and 4‐substituted‐3‐nitropyridines have been substituted with ammonia and amines by the vicarious nucleophilic substitution (VNS) method with ammonia and amines and by the oxidative substitution method in the position para to the nitro group. High regioselectivities and yields have been obtained in both cases to afford a series of 4‐substituted‐2‐alkylamino‐5‐nitropyridines. The VNS method has also been used in alkylation reactions with 3‐nitropyridines to form dichloromethyl‐and alkoxycarbomethyl‐β‐nitropyridines. From the appropriate substituted nitropyridines imidazopyridines and azaindoles have been formed.     

Rapid Access for the Synthesis of 1‐N‐Methyl‐spiro[2.3′]oxindole‐spiro[3.7″] (3″‐Aryl)‐5″‐methyl‐3″,3a″,4″,5″,6″,7″‐hexahydro‐2H‐pyrazolo[4,3‐c]pyridine‐4‐aryl‐pyrrolidines Through Sequential 1,3‐Dipolar Cycloaddition and Annulation

The 1,3‐dipolar cycloaddition of an azomethine ylide, generated from isatin and sarcosine by a decarboxylative route with various p‐substituted 3,5 bis(aryl methylidene)N‐methyl‐4‐piperidinones in refluxing methanol, proceeded regioselectively to give novel dispiroheterocycles. The product on subsequent annulation with hydrazine hydrate afforded 1‐N‐methyl‐spiro[2.3′]oxindole‐spiro[3.7″](3″‐aryl)‐5″‐methyl‐3″,3a″,4″,5″,6″,7″‐hexahydro‐2H‐pyrazolo[4,3‐c]pyridine‐4‐aryl‐pyrrolidines in good yield.     

Reactions with dimethylformamide‐dimethylacetal: Synthesis and reactions of several new pyridine and pyrazolo[3,4‐b]pyridine derivatives

6‐Aminopyridine‐2(1H)‐thiones 1a,b reacted with dimethylformamide‐dimethylacetal (DMF‐DMA) to give the corresponding 6‐{[(N,N‐dimethylamino)methylene]amino}pyridine derivatives 2a,b . The latter compounds reacted with hydrazine hydrate to afford the 3,6‐diamino‐1H‐pyrazolo[3,4‐b]pyridine derivative 4 and 3‐amino‐5‐hydrazino‐1H‐pyrazolo[4′,3′:5,6]pyrido[2,3‐d]pyrimidine derivative 7 , respectively. Compound 4 condensed with DMF‐DMA to yield the 3,6‐bis{[(N,N‐dimethylamino)methylene]amino}‐1H‐pyrazolo[3,4‐b]pyridine derivative 10 , which reacted with malononitrile to give the corresponding pyridopyrazolopyrimidine derivative 15 . © 2007 Wiley Periodicals, Inc. Heteroatom Chem 18:399–404, 2007; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20312     

Effect of Bulkiness on Reversible Substitution Reaction at MnII Center with Concomitant Movement of the Lattice DMF: Observation through Single‐Crystal to Single‐Crystal Fashion

The porous coordination polymer ({[Mn(L)H₂O](H₂O)_1.5(dmf)}_n, 1 ) (DMF=N,N‐dimethylformamide) exhibits variety of substitution reactions along with movement of lattice DMF molecule depending upon bulkiness of the external guest molecules. If pyridine or 4‐picoline is used as a guest, both lattice and coordinated solvent molecules are simultaneously substituted (complexes 6 and 7 , respectively). If a bulky guest like aniline is used, a partial substitution at the metal centers and full substitution at the channels takes place (complex 8 ). If the guest is 2‐picoline (by varying the position of bulky methyl group with respect to donor N atom), one Mn^II center is substituted by 2‐picoline, whereas the remaining center is substituted by a DMF molecule that migrates from the channel to the metal center (complex 9 ). Here, the lattice solvent molecules are substituted by 2‐picoline molecules. For the case of other bulky guests like benzonitrile or 2,6‐lutidine, both the metal centers are substituted by two DMF molecules, again migrating from the channel, and the lattice solvent molecules are substituted by these guest molecules (complex 10 and 11 , respectively). A preferential substitution of pyridine over benzonitrile (complex 12 ) at the metal centers is observed only when the molar ratio of PhCN:Py is 95:5 or less. For the case of an aliphatic dimethylaminoacetonitrile guest, the metal centers remain unsubstituted (complex 13 ); rather substitutions of the lattice solvents by the guest molecules take place. All these phenomena are observed through single crystal to single crystal (SC–SC) phenomena.     

Synthesis,Reactions, and Spectral Characterization of New Fused Pyrazolothienopyridine and Pyrazolopyrrolopyridine Systems

4‐Oxo‐1‐phenyl‐4,7‐dihydropyrazolo[3,4‐b ]pyridine‐5‐carbonitrile compound ( 4 ) was prepared by the reaction of 5‐amino‐3‐methyl‐1‐phenyl pyrazole ( 1 ) with ethyl 2‐cyano‐3‐ethoxyacrylate followed by cyclization using diphenyl ether. The pyrazolopyridinone compound 4 was converted to the chloropyrazolopyridine 5 by the reaction with phosphorus oxychloride. Compound 5 was used as a starting material to synthesize 3‐amino‐4‐substituted pyrazolothienopyridine derivatives 10a–f and ethyl‐3‐aminopyrazolopyrrolopyridine‐2‐carboxylate 21 , which were used as a versatile precursors for synthesis of poly‐fused heterocyclic compounds.     

Synthesis and Spectroscopic Characterization of Some Ferrocenyl Schiff Bases Containing Pyridine Moiety and Their Complexation with Cobalt,Nickel, Copper and Zinc

Three novel ferrocenyl Schiff base ligands containing pyridine moiety have been formed by 1:2 molar condensation of 1,1′‐diacetylferrocene with 2‐aminopyridine, 2‐amino‐5‐picoline or 2‐amino‐5‐chloropyridine, respectively. The ligands are 1,1′‐bis[1‐(pyridyl‐2‐imino)‐ethyl]ferrocene (L1); 1,1′‐bis[1‐(5‐methyl‐pyridyl‐2‐imino)ethyl]ferrocene (L2) and 1,1′‐bis[1‐(5‐chloropyridyl‐2‐imino)ethyl]ferrocene (L3). These ligands form 1:1 complexes with Co(II), Cu(II), Ni(II) and Zn(II) ions. The prepared ligands and their complexes have been characterized by IR, ¹H NMR, ¹³C NMR, UV/Vis spectra as well as elemental analysis. The spectral data of the ligands and their complexes are discussed in connection with the structural changes due to complexation.     

Microwave‐assisted synthesis and characterization of heterocyclic,and optically active poly(amide‐imide)s incorporating L‐amino acids

N,N′‐Pyromelliticdiimido‐di‐L ‐alanine ( 1 ), N,N′‐pyromelliticdiimido‐di‐L ‐phenylalanine ( 2 ), and N,N′‐pyromelliticdiimido‐di‐L ‐leucine ( 3 ) were prepared from the reaction of pyromellitic dianhydride with corresponding L ‐amino acids in a mixture of glacial acetic acid and pyridine solution (3/2 ratio) under refluxing conditions. The microwave‐assisted polycondensation of the corresponding diimide‐diacyl chloride monomers ( 5–7 ) with 4‐phenyl‐2,6‐bis(4‐aminophenyl) pyridine ( 10 ) or 4‐(p‐methylthiophenyl)‐2,6‐bis(4‐aminophenyl) pyridine ( 12 ) were carried out in a laboratory microwave oven. The resulting poly(amide‐imide)s were obtained in quantitative yields, and they showed admirable inherent viscosities (0.12–0.55 dlg^?1), were soluble in polar aprotic solvents, showed good thermal stability and high optical purity. The synthetic compounds were characterized by IR, MS, ¹H NMR, and ¹³C NMR spectroscopy, elemental analysis, and specific rotation. Copyright © 2008 John Wiley & Sons, Ltd.     

Efficient asymmetric addition of diethylzinc to aldehydes using C2‐novel chiral pyridine β‐amino alcohols as chiral ligands

A series of novel C₂‐symmetric chiral pyridine β‐amino alcohol ligands have been synthesized from 2,6‐pyridine dicarboxaldehyde, m‐phthalaldehyde and chiral β‐amino alcohols through a two‐step reaction. All their structures were characterized by ¹H NMR, ¹³C NMR and IR. Their enantioselective induction behaviors were examined under different conditions such as the structure of the ligands, reaction temperature, solvent, reaction time and catalytic amount. The results show that the corresponding chiral secondary alcohols can be obtained with high yields and moderate to good enantiomeric excess. The best result, up to 89% ee, was obtained when the ligand 3c (2S,2′R)‐2,2′‐((pyridine‐2,6‐diylbis(methylene))bisazanediyl))bis(4‐methyl‐1,1‐diphenylpentan‐1‐ol) was used in toluene at room temperature. The ligand 3g (2S,2′R)‐2,2′‐((1,3‐phenylenebis(methylene))bis(azanediyl))bis(4‐methyl‐1,1‐diphenylpentan‐1‐ol) was prepared in which the pyridine ring was replaced by the benzene ring compared to 3c in order to illustrate the unique role of the N atom in the pyridine ring in the inductive reaction. The results indicate that the coordination of the N atom of the pyridine ring is essential in the asymmetric induction reaction. Copyright © 2014 John Wiley & Sons, Ltd.     

On the Reaction of Thiazole‐2,4‐diamines with Isothiocyanates – Preparation and Transformation of 2,4‐Diaminothiazole‐5‐carbothioamides

In the reaction of thiazole‐2,4‐diamines 8 with isothiocyanates 1 , 2,4‐diaminothiazole‐5‐carbothioamides 9, 10, 18 , and 19 as well as thiazolo[4,5‐d]pyrimidine‐7(6H)‐thiones 21 were formed. The carbothioamides 9, 10 , and 18 were transformed by reaction with different types of monofunctional and bifunctional electrophiles into hitherto unknown acceptor‐substituted 4,4′‐([2,5′‐bithiazole]‐2′,4′‐diyl)bis[morpholines] 24 and 29 , the 2′,4′‐bis(dialkylamino)[2,5′‐bithiazol]‐4‐(5H)‐ones 30 , and the 4‐substituted 2′,4′‐bis(dialkylamino)‐2,5′‐bithiazoles 31 . From 30 and 31 new 4‐mono‐ or 4,5‐disubstituted 2′,4′‐bis(dialkylamino)‐2,5′‐bithiazoles 34, 35, 38 , and 39 as well as 5‐substituted 2′,4′‐bis(dialkylamino)[2,5′‐bithiazol]‐4(5H)‐ones 33, 36 , and 37 were prepared.     

Design,Synthesis and Antitumor Activity of Asymmetric Bis(s‐triazole Schiff‐base)s Bearing Functionalized Side‐Chain

1‐Amino‐2‐pyrid‐3‐yl‐5‐(2‐benzoylethylthio)‐s‐triazole ( 1 ) was condensed with 1‐amino‐3‐mercapto‐5‐ [(un)substituted phenyl]‐s‐triazoles and subsequently substituted with chloroacetic acid to afford bis‐s‐triazole sulfanylacetic acid mono‐Schiff bases ( 3a – 3e ), which were condensed with 9‐formylanthracene to produce asymmetric bis(s‐triazole Schiff base) sulfanylacetic acids ( 4a – 4e ). The structures of new synthesized compounds were characterized by elemental analysis and spectral data, and their in vitro antitumor activity against L1210, CHO and HL60 cell lines was evaluted via the respective IC₅₀ values by methylthiazole trazolium (MTT) assay.     

Piperidine‐mediated synthesis of thiazolyl chalcones and their derivatives as potent antimicrobial agents

A series of new thiazolyl chalcones, 1‐[2‐amino‐4‐methyl‐1, 3‐thiazol‐5‐yl]‐3‐aryl‐prop‐2‐en‐1‐one were prepared by piperidine mediated Claisen‐Schmidt condensation of thiazolyl ketone with substituted aromatic aldehyde. These chalcones on cyclization gave 2‐amino‐6‐(2‐amino‐4‐methyl‐1,3‐thiazol‐5‐yl)‐4‐aryl‐4H‐pyridine‐3‐carbonitrile and 2‐amino‐6‐(2‐amino‐4‐methyl‐1,3‐thiazol‐5‐yl)‐4‐aryl‐4H‐pyran‐3‐carbonitrile. The results showed that this skeletal framework exhibited marked potency as antimicrobial agents. The most active antibacterial agent was 2‐amino‐6‐(2‐amino‐4‐methyl‐1,3‐thiazol‐5‐yl)‐4‐(4‐chlorophenyl)‐4H‐pyran‐3‐carbonitrile while 2‐amino‐6‐(2‐amino‐4‐methyl‐1,3‐thiazol‐5‐yl)‐4‐(4‐methoyphenyl)‐4H‐pyran‐3‐carbonitrile appeared to be the most active antifungal agent. J. Heterocyclic Chem., (2011).