Novel rearrangements of fused zwitterionic heterocyclic systems

(E)-2-Chlorodimethylstannyl-3-diethylboryl-2-pentene (1) reacts with the C-lithiated azoles 2 (derived from thiazole (2a), 4-methylthiazole (2b), 1,4-dimethylimidazole (2c), benzoxazole (2d) and benzthiazole (2e)) to eliminate LiCl, giving first mixtures containing compounds with either a coordinative N--- bond (3) or the zwitterionic isomer with an Sn---N bond (4), or both, and in some cases a rearranged product (5) with a 1,2,5-azastannaborole unit is also present. The zwitterionic compounds 4 tend to rearrange into the heterocycles 5 in which the heteroaromatic system is no longer present and two new C---C bonds, a new B---C and a new B---N bond are formed. The reactions were monitored by multinuclear NMR (¹H, ¹¹B, ¹³C, ¹⁴N and ¹¹⁹Sn NMR) which also served for the characterization of the final products. In the case of 5e, the molecular structure was determined by single-crystal X-ray analysis (monoclinic; space group P2₁/n; A=11.691(2), B=12.396(2), C=13.149(2) Å; β=93.41(2)°).     

Syntheses of C12,N13 heterocyclic bridged fused indenopyrrolocarbazoles

Tandem alkylation/cyclization of indenopyrrolocarbazole 4a, a C12 carbon analogue of indolocarbazole K252c, was carried out by general solid-phase and solution-phase methods. Alkylation of fused pyrroloindenylcarbazole 4a derivatives with appropriate monoacetals of diketones afforded the corresponding C12-substituted acetal alcohols. Acid-catalyzed cyclization of these adducts yielded C12,N13-bridged tetrahydrofuran, pyran, and dioxane compounds 10-13.     

CuI mediated synthesis of heterocyclic flavone-benzofuran fused derivatives

An efficient synthetic method of heterocyclic flavone benzofuran fused derivatives is reported in good to excellent yield (75–90%) via Ullmann type coupling reaction. The protocol involves catalytic amount of CuI (10 mol%) and K₂CO₃ base for the intramolecular CO bond formation under mild reaction conditions.     

Synthesis of some fused heterocyclic systems and their nucleoside candidates

A series of pyridofuro compounds were synthesized from 4-(4-chlorophenyl)-1,2-dihydro-2-oxo-6-(thiophen-2-yl)pyridine-3-carbonitrile (1) as starting material. Alkylation of 1 with ethyl bromoacetate gave the corresponding ester 2, which was condensed with hydrazine hydrate to afford the corresponding acid hydrazide derivative 3. Thrope-Ziegler cyclization of 2 with sodium methoxide gave furo[2,3-b]pyridine derivative 4, which was reacted with thiosemicarbazide, allyl isothiocyanate, formamide or hydrazine hydrate to give furopyridine derivatives 5–8, respectively. The latter compound 8 was cyclized with acetylacetone or formic acid to give the corresponding compounds 9 and 10, respectively. Furthermore, sulfurization of 1 with P₂S₅ gave the corresponding thioxopyridine 11, which was reacted with glycosyl (or galactosyl) bromide, morpholine or piperidine to give the corresponding thioglycoside 12a,b and Mannich base 14a,b derivatives. The deacetylation of 12a,b gave the corresponding deacetylated thioglycosides 13a,b, respectively. All the newly synthesized compounds were characterized by the elemental analyses and spectroscopic evidences (IR, ¹H- and ¹³C NMR).     

Synthesis of fused purinoquinazolines. Three new heterocyclic ring systems

The Ullmann reaction of 8-aminotheophylline or 8-aminocaffeine with 2-chlorobenzoic acid and of 8-bromotheophylline with ethyl-2-aminobenzoate afforded derivatives of three new heterocyclic systems: purino[7,8-α]quinazoline-5,9,11(6H,8H,10H)-trione, purino[8,9-b]quinazoline-2,4,11(1H,3H,5H)-trione and purino[8,7-b]quinazoline-2,4,6(1H,3H,11H)-trione, respectively.     

New fused pyrazolopyrimidine derivatives; heterocyclic styling,synthesis, molecular docking and anticancer evaluation

Novel pyrazolopyrimidines and their fused derivatives derived from aminopyrazole moiety as pyrazoloquinazoline, chromenopyrazolopyrimidine, pyrazolopyrimidopyrimidine, pyrazolopyrimidotriazepine and benzoimidazopyrazolopyrimidine were designed, synthesized and evaluated for their anticancer activities. Twenty of the synthesized compounds were tested by the National Cancer Institute (NCI, Bethesda, USA) at a single high dose (10^-5 M). It was found that 5-amino-1H-pyrazole-4-carbonitrile derivative, pyrazolo[5,1-b]quinazoline-11-carbonitrile derivative and 1-amino-2,4-dihydro-5H-benzo[4,5]imidazo[1,2-c]pyrazolo[4,3-e]pyrimidin-5-one were own widely selective powerful anticancer activity towards certain cancer cell lines and this also proved through docking studies with cyclooxygenase-2 (COX-2) enzyme.     

Synthesis of fused nonaromatic heterocyclic systems based on dioxolanones and hydrazine

Transformations of N-aminooxazolidinones were studied. These transformations occur by different pathways depending on the reaction conditions and the structure of the starting compound. Heating of N-aminooxazolidinones in an acidic medium leads to the ring expansion to form 1,3,4-oxadiazin-2-ones. The treatment of N-benzoylamino-and N-benzylamino-oxazolidinones with polyphosphoric acid (PPA) affords tricyclic structures, viz., phthalazine derivatives. In the reactions with PPA, 5-(2-phenylethyl)-substituted N-aminooxazolidinones and 6-(2-phenylethyl)-substituted oxatetrahydropyridazin-2-ones undergo intramolecular amidoalkylation to form compounds containing the tetrahydronaphthalene fragment. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2156–2163, December, 2006.     

Synthesis of novel heterocyclic fused 1,3-diazabuta-1,3-dienes and accompanying rearrangements in their cycloaddition reactions with ketenes: synthesis of heterocyclic fused pyrimidinone derivatives

The reactions of 1,3-diazabuta-1,3-dienes 1 with 2-aminothiophenol have been shown to result in excellent yields of N-benzothiazol-2-yl-N′-aryl benzamidines 2. Their regioselective [4+2] cycloadditions with various ketenes are shown to yield novel benzothiazolo pyrimidinones 4. A similar and convenient protocol for the synthesis of bisthiosubstituted 1,3-diazabuta-1,3-dienes 8 and 9 and interesting rearrangements accompanying their [4+2] cycloadditions with a number of ketenes are described.     

Convenient synthesis of fused heterocycles from α-ketohydroximoyl chlorides and heterocyclic amines

Nitroso derivatives of imidazo[1,2-a]pyridine ( 11, 13, 14 ), imidazo[1,2-a]pyrimidine ( 15 ), imidazo[1,2-a]pyrazine ( 16 ), imidazo[1,2-b]pyrazole ( 17 ), and imidazo[1,2-b]-1,2,4-triazole ( 19 ) were obtained in good yields from α-ketohydroximoyl chlorides 3 and 2-aminopyridines ( 4–6 ), 2-aminopyrimidine ( 7 ), 2-aminopyrazine ( 8 ), 5-amino-3-phenylpyrazole ( 9 ), and 3-amino-2H-1,2,4-triazole ( 10 ), respectively. Under different conditions, the reaction of 3 with 3-amino-2H-1,2,4-triazole ( 10 ) and 2-aminopyrazine ( 8 ) afforded the noncyclized substitution products 18 and 22 , respectively. The structures of the products were assigned and confirmed on the basis of their elemental analyses, spectral data, and alternate synthesis wherever possible.     

Diethyl acetonedicarboxylate — a precursor for the synthesis of new substituted 4-aminoquinolines and fused 4-aminopyridines

Summary The reaction of cyclic enaminonitriles1 with diethyl acetonedicarboxylate (2) affords fused 4-amino-3-ethoxycarbonyl-2-ethoxycarbonylmethyl-pyridines4. The course of the reaction and the yield of cyclic products were promoted by tin(IV)chloride. N-substituted diethyl 3-aminoglutaconates3 seem to be intermediates of the cyclization reaction.Dedicated to Prof.Milan Kratochvil on the occasion of his 70th birthday     

N,O-ditosylethanolamine as effective reagent for the synthesis of heterocyclic tertiary amine salts

During the synthesis of N-tosylaziridine, two unexpected products were isolated: 1-(2-(p-tolylsulfonamido)ethyl)pyridinium p-tolylsulfonate (3) and N,N,O-tri-(p-tolylsulfonyl)ethanolamine (3a). The structures of 3 and 3a were investigated in solid state by X-ray analysis. A new family of related salts was obtained using an efficient and facile one-pot synthesis consisting in the interaction between various nitrogen heterocycles and N,O-ditosylethanolamine.     

An overview on the copper-promoted synthesis of five-membered heterocyclic systems

The development of novel approaches for the preparation of small-sized heterocyclic products has remained an extremely attractive but challenging proposition. Copper has been known as one of the most applicable and significant transition metals utilized in the synthesis of organic products. A couple of factors such as high earth abundance and versatile catalysis resulted in the growth of copper-promoted synthesis of five-membered heterocyclic products. Utilizations such as making coins and electrical equipment express the importance of copper, as well. Here, a comprehensive overview of the copper-catalyzed synthesis of five-membered heterocyclic products is presented, focusing on the developments over the past 4 years.     

Pot,atom and step economic synthesis of fused three heterocyclic ring compounds under microwave irradiation in water

A new series of fused three heterocyclic ring compounds, consisting of a pyrazolo (ring A), a pyridine (ring B), and a pyrimidine (ring C) core, pyrazolo[4′,3′:5,6]pyrido[2,3‐d]pyrimidine derivatives were successfully synthesized by pot, atom and step economic (PASE) method under microwave irradiation in the presence of p‐toluene sulphonic acid in water.     

Research on heterocyclic compounds. XXIII. Phenyl derivatives of fused imidazole systems

The reaction of various heteroarylamines with ethyl 2-benzoyl-2-bromoacetate was used to obtain some imidazo[1,2-a]pyridines, imidazo[1,2-a]pyrimidines, imidazo[2,1-b]thiazoles and imidazo[2,1-b]benzothiazoles characterized by the presence of a phenyl moiety on the imidazole ring. In the case of thiazole and benzothiazole derivatives, unexpected by-products were isolated and their structures elucidated.     

Regioselective synthesis of fused ring heterocyclic derivatives of ketene aminals and their biological activities

A regioselective and convenient methodology was developed to synthesize heterocyclic derivatives, bearing imidazole, piperidines, and azepines rings. The N-arylnitrones derived from 3-formylchromones were selected to react with heterocyclic ketene aminal to furnish the structurally attractive and pharmacologically important fused ring heterocycles. The N-arylnitrone moiety of 3-formylchromone was used to activate the formyl group for regioselective fused ring heterocycles synthesis, whereas, the effect of substituents at aryl functionality of nitrones were studied to improve the yield of target fused ring heterocyclic products. The synthesized compounds (10-12) were evaluated for their in vitro cytotoxic and antifungal influences. In cytotoxic (brine shrimp lethality) assay, compound 11e was found to be active with LD₅₀ = 4.1 × 10⁻⁶ μg/mL.     

An efficient non-catalytic, regioselective approach to the synthesis of angularly fused polycyclic systems

A novel approach to the synthesis of partially reduced different ring sizes of PAH analogs with sec.amino and nitrile functionalities is delineated through base-induced ring transformation of 4-sec.amino-2-oxo-5,6-dihydro-2H-benzo[h]chromene-3-carbonitriles by a carbanion, generated in situ from cyclopentanone, cyclohexanone, cycloheptanone, and cyclooctanone separately in good yields. An increase in the size of cycloalkanone ring beyond cyclooctanone restricts the ring transformation under analogous reaction conditions possibly due to bulky conformation of higher homologs. The synthetic method provides an efficient general route for the construction of angularly fused partially reduced polycyclic aromatic hydrocarbons: 5-sec.amino-2,3,6,7-tetrahydro-1H-cyclopenta[c]phenanthrene-4-carbonitriles, 6-sec.amino-2,3,4,7,8-pentahydro-1H-benzo[c]phenanthrene-5-carbonitriles, 7-sec.amino-2,3,4,5,8,9-hexahydro-1H-cyclohepta[c]phenanthrene-6-carbonitriles, and 8-sec.amino-2,3,4,5,6,9,10-heptahydro-1H-cycloocta[c]phenanthrene-7-carbonitriles.     

Aryne intermediates in the synthesis of polynuclear heterocyclic systems (Review)

Published examples of the polynuclear fused heterocyclic systems production by cycloaddition reactions involving aryne intermediates generated in situ are reviewed.     

4-Quinolone fused heterocyclic ring systems by intramolecular reactions of 4-quinolone-2-carboxamides

A versatile synthetic route to new 4-quinolone-based polycyclic systems is described. TFA-catalyzed intramolecular reaction of N-unsubstituted quinolone-2-carboxylic acid amides gives structurally diverse compounds, depending on the length of the chain. Acid treatment of β-oxoamides furnishes 3H-pyrazino[1,2-a]quinoline-4,6-diones, due to the nucleophilic attack of N-1 to the carbonyl group, whereas TFA treatment of δ- and ε-oxoamides leads to the formation of tetracyclic compounds by a tandem heteroannulation reaction.     

Syntheses of heterocyclic fused thiazolecarboxylic acids I

A number of thiazolo 5-carboxylic acid derivatives were prepared which were fused to other heterocycles such as 1,2,4-benzothiadiazine, quinazoline, and pyrimidine rings at the 2,3-position of the thiazole ring. In several instances unexpected products were obtained, depending on the reaction conditions. The chemistry of these reactions and the identification of the products are discussed.     

Use of sulfonium ylides in the synthesis of heterocyclic systems (review)

The literature on the use of sulfur ylides in the synthesis of heterocyclic systems of varied structure is reviewed. The possible preparative value of these reactions is discussed.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 147–173, February, 1990.