Copper-catalyzed intramolecular C–N bond formation reaction of 3-amino-2-(2-bromophenyl)dihydroquinazolinones: synthesis of indazolo[3,2-b]quinazolinones

A copper-catalyzed intramolecular C–N bond formation reaction of 3-amino-2-(2-bromophenyl)dihydroquinazolinones has been developed for the synthesis of indazolo[3,2-b]quinazolinones in moderate to good yields. The structure of the newly synthesized indazolo[3,2-b]quinazolinones was unambiguously confirmed by X-ray single-crystal diffraction analysis. Moreover, a possible mechanism for the formation of indazolo[3,2-b]quinazolinones is discussed.     

Aryne [3 + 2] cycloaddition with N-sulfonylpyridinium imides and in situ generated N-sulfonylisoquinolinium imides: a potential route to pyrido[1,2-b]indazoles and indazolo[3,2-a]isoquinolines

The aryne [3 + 2] cycloaddition process with pyridinium imides breaks the aromaticity of the pyridine ring. By equipping the imide nitrogen with a sulfonyl group, the intermediate readily eliminates a sulfinate anion to restore the aromaticity, leading to the formation of pyrido[1,2-b]indazoles. The scope and limitation of this reaction are discussed. As an extension of this chemistry, N-tosylisoquinolinium imides, generated in situ from N'-(2-alkynylbenzylidene)-tosylhydrazides via an AgOTf-catalyzed 6-endo-dig electrophilic cyclization, readily undergo aryne [3 + 2] cycloaddition to afford indazolo[3,2-a]-isoquinolines in the same pot, offering a highly efficient route to these potential anticancer agents.     

Functional derivatives of thiophene

A method is proposed for the synthesis of isatin analogs — 4,5-dioxothieno[2,3-b] pyrroles and 5,6-dioxothieno[3,2-b]pyrroles — by reaction of oxalyl chloride with amino-substituted α-amino- and Β-aminothiophene. The thiosemicarbazones of 4-ary1-5,6-dioxothieno[3,2-b]pyrroles were synthesized. n]mis|See [1] for communication X.     

Synthesis of novel 2,8-disubstituted indolo[3,2-b]carbazoles

A new synthetic pathway towards 2,8-difunctionalised indolo[3,2-b]carbazoles was investigated. The presented method offers a short and high yielding route towards 2,8-dibromo-5,11-dihexyl-6,12-diphenyl-indolo[3,2-b]carbazole. It is demonstrated that the latter compound is a versatile building block, enabling the synthesis of a number of previously unreported 5,11-dialkyl-6,12-diphenyl-indolo[3,2-b]carbazoles in moderate to good yields, using Suzuki and Sonogashira cross-coupling reaction. Furthermore it is shown that 2,8-dibromo-5,11-dihexyl-6,12-diphenyl-indolo[3,2-b]carbazole can be easily formylated, giving rise to the 2,8-diformyl-5,11-dihexyl-6,12-diphenyl-indolo-[3,2-b]carbazole. The latter compound was successfully subjected to condensation reactions.     

Donor-acceptor copolymers from cyclopentannulation polymerizations with dicyclopenta[cd,jk]pyrene and dicyclopenta[cd,lm] perylene acceptors

A series of donor-acceptor copolymers with dicyclopenta[cd,jk]pyrene and dicyclopenta[cd,lm]perylene acceptor units was prepared via palladium catalyzed cyclopenta-annulation reactions. The acceptor units were paired with diethynyl containing donor groups based on benzo[1,2-b:4,5-b’]dithiophene, thieno[3,2-b]thiophene, and 4-octyl-4H-dithieno[3,2-b:2′,3′-d]pyrrole to create six polymer variants. The cyclopentannulation polymerization resulted in copolymers with molecular weights (Mn) of 6–14 kDa and broad light absorption in the visible region with band gaps of 1.38–1.85 eV. The synthetic methodology, as well as optoelectronic properties, including thin-film absorption and cyclic voltammetry, of the donor-acceptor copolymers are presented.     

Heterocycles containing nitrogen and sulfur. Part 49. Synthesis of derivatives of new heterocyclic systems: 1,2-Dioxocyclopenta(hexa)[g]oxazolidino-[3,2-f] pyrimido[4,5-b][1,4]thiazine, 1,2-dioxocyclopenta(hexa)-[g] imidazolidino[3,2-f]pyrimido[4,5-b][1,4]thiazine, and 1,2-oxazino[5,4-g]pyrimidino[4,5-b][1,4]thiazine

The reaction of 4-methoxy-5-amino-6-mercaptopyrimidine with 2-oxo-1-chlorocyclopentyl(hexyl)glyoxalate esters gave derivatives of the previously unknown tetracyclic systems 1,2-dioxocyclopenta (hexa)[g]oxazolidino[3,2-f]pyrimido[4,5-b][1,4]thiazines, which are transformed by ammonium acetate into derivatives of 1,2-dioxocyclopenta(hexa) [g]imidazolidino[3,2-f]pyrimido[4,5-b]-[1,4] thiazines. Derivatives of the new tricyclic 1-oxazino [5,4-g]pyrimido[4,5-b][1,4]thiazine system were obrtained by reaction of 6-carbethoxy-7-acetylpyrimido [4,5-b] [1,4] thiazines with hydroxylamine.     

Synthesis, structures, and properties of disubstituted heteroacenes on one side containing both pyrrole and thiophene rings

A new series of ladder-type heteroacenes containing both pyrrole and furan rings, 5,6-disubstituted diindolo[3,2-b:4,5-b']thiophenes (DITs), were effectively synthesized from N-functionalized 3,3'-dibromo-2,2'-biindoles undergoing intramolecular cyclization with bis(phenylsulfonyl) sulfide and organolithium. Single-crystal X-ray results demonstrate that 5,6-dipropyldiindolo[3,2-b:4,5-b']thiophene (4b) forms a herringbone-type of packing motif and 5,6-di(p-tolyl)diindolo[3,2-b:4,5-b']thiophene (4d) forms a parallel packing motif. Both of them have S-S contacts, enhancing the electronic transport between molecules. Their photophysical properties suggest that the skeleton of diindolo[3,2- b:4,5-b']thiophene is more favorable to aggregate in solid than that of indolo[3,2-b]carbazole. The large band gaps and low-lying HOMO energy levels could result in much better stability.     

A new route to annulated oligothiophenes

[reaction: see text] A new convenient method for the construction of thiophene-annulated thieno[2,3-b]thiophenes has been proposed. The key step of the method is ring closure of 10H-bisthienodithiocin-10-one by strong bases. The syntheses of two previously unknown annulated oligothiophenes, thieno[2,3-b]thieno[3',2':4,5]thieno[3,2-d]thiophene (1a) and thieno[3,2-b]thieno[2',3':4,5]thieno[3,2-d]thiophene (1b), have been described to illustrate the success of the method.     

One-pot four-component domino reaction for the synthesis of bifunctionalized spiro[indazolo[3,2-b]quinazoline-7,3′-indoline hybrids: A green approach

An efficient tandem route to obtain novel spiro[indazolo[3,2-b]quinazoline-7,3′-indolines has been explored. The one-step domino reaction proceeds via in situ generation of the 1H-indazol-3-amines followed by its reaction with the cyclic 1,3-dicarbonyls and isatin derivatives to furnish complex N-fused spiro-polyheterocyclic frameworks. This protocol describes a valuable route to concisely and feasibly obtain spiro[indazolo[3,2-b]quinazoline-7,3′-indolines from isatin derivatives. The present protocol is particularly attractive because of the following features: group-assisted-purification (GAP) chemistry process, low-cost solvent, convenience of operation, excellent atom economy, and high yields.     

Direct construction of 3',4'-dihydrospiro[pyrrol-3,2'-oxindoles] through a cascade Michael/cyclization reaction of 3-aminoindolin-2-ones with enones/enals

A simple and efficient cascade Michael/cyclization reaction of 3-aminoindolin-2-ones with enones/enals was identified for the synthesis of potentially biologically active 3',4'-dihydrospiro[pyrrol-3,2'-oxindoles], using DBU as an efficient catalyst and ethylene glycol as an environmentally benign solvent. More diverse 3',4'-dihydrospiro[pyrrol-3,2'-oxindoles] analog libraries were prepared in good yields (up to 97%). The structure of 3',4'-dihydrospiro[pyrrol-3,2'-oxindoles] was confirmed by mass spectrometry analysis, NMR analysis and single crystal X-ray diffraction. The main advantages of this method include the availability of startingmaterials, simple experimental operation, short reaction time, as well as high yields observed.     

Reductive cyclization of 1-(2-nitroaryl)isoquinoline derivatives

Isoquinoline derivatives 3b and 3c were prepared and their triethyl phosphite mediated reductive cyclization reactions investigated. Only the indazolo[3,2-a]isoquinolines 4b and 4c were formed.     

Planar beta-linked oligothiophenes based on thieno[3,2-b]thiophene and dithieno[3,2-b:2',3'-d]thiophene fused units

A series of planar beta-linked oligothiophenes based on thieno[3,2-b]thiophene and dithieno[3,2-b:2',3'-d]thiophene fused units were synthesized. The optical data indicate a blue shift of the absorption maximum in comparison to the alpha-linked analogues due to cross-conjugation between fused rings. The crystal structures of 3,3'-bi(thieno[3,2-b]thiophene) and 3,3';6',3"-ter(thieno-[3,2-b]thiophene) reveal edge-to-face pi-stacked dimer motifs, whereas the crystal structure of 3,3'-bis(dithieno[3,2-b:2',3'-d]thiophene) consists of face-to-face pi-stacked molecules. [structure: see text]     

Photochromic oligothienoacene derivatives with photo-switchable luminescence properties and computational studies

Photochromic thieno[3,2-b]thiophenes and dithieno[3,2-b:2',3'-d]thiophene with photo-switchable luminescence properties have been synthesized using a Suzuki cross-coupling reaction; their electronic structures, and photochromic and luminescence behaviour have also been studied.     

Synthesis and polymerization of 2,5-dimethylene-2,5-dihydrothieno[3,2-b]thiophene derivatives: The structure and reactivity of quinonoid monomers

Novel 2,5-dimethylene-2,5-dihydrothieno[3,2-b]thiophene derivatives such as 2,5-bis[di(ethylthio)methylene]-2,5-dihydrothieno[3,2-b]thiophene ( 4b ) and 2,5-bis[cyano(ethylthio)methylene]-2,5-dihydrothieno[3,2-b]thiophene ( 4c ) were successfully synthesized as isolable crystals. Polymerization behavior of 2,5-bis(dicyanomethylene)-2,5-dihydrothieno[3,2-b]thiophene ( 4a ), 4b , and 4c was investigated. 4a , 4b , and 4c are not homopolymerizable with any initiators and also not copolymerizable with vinyl monomers such as styrene (St), methyl methacrylate, and acryronitrile except for an alternating copolymerization of 4a with St. 4a , 4b , and 4c did not copolymerize with 7,8-bis(butoxycarbonyl)-7,8-dicyanoquinodimethane (BCQ) as a highly conjugated comonomer and instead only homopolymer of BCQ was obtained, indicating that they are much less reactive than BCQ. To obtain the relative reactivity among 1c , 2c , and 4c , the rate of addition reaction of 2,2′-azobis(isobutyronitrile) (AIBN) with 4c was compared with those of AIBN with 7,8-bis(ethylthio)-7,8-dicyanoquinodimethane ( 1c ) and with 2,5-bis[cyano(ethylthio)methylene]-2,5-dihydrothiophene ( 2c ) by NMR spectroscopy and analyzed with the first-order kinetics. The relative reactivity among 1c , 2c , and 4c was found to be as follows: 1c > 4c > 2c . The relationship between structure and reactivity for the quinonoid compounds was discussed. © 1999 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 37: 3027–3039, 1999     

Total synthesis of dysiherbaine

A convergent total synthesis of the marine natural product dysiherbaine was accomplished. The key steps of the synthesis are an alkylation at the gamma-carbon of a protected glutamate with a highly substituted pyran derived from mannose, which was followed by a ring-contraction cascade reaction, which simultaneously gave the tetrasubstituted carbon and the hexahydrofuro[3,2-b]pyran ring system of the natural product.     

Mild and efficient Winterfeldt oxidation of 1,2,3,4-tetrahydro-γ-carbolines for the synthesis of dihydropyrrolo[3,2-b]-quinolones and pyrrolo[3,2-b]quinolones

The Winterfeldt oxidation (NaOH, DMF, air, rt) of substituted 1,2,3,4-tetrahydro-γ-carbolines has been developed, which provides a convenient and efficient method for the synthesis of the corresponding dihydropyrrolo[3,2-b]quinolones in moderate to excellent yields (38-94%). The generality and substrate scope of this reaction are explored and a possible mechanism is proposed. The results imply that electron-withdrawing groups on N2 of tetrahydro-γ-carbolines and N5-H are necessary. The synthesis of 5 or 7-substituted pyrrolo[3,2-b]quinolones in near quantitative yields was also achieved through deprotection and aromatization of N1-Boc-dihydropyrrolo[3,2-b]quinolones.     

Condensed isoquinolines 24. Reaction of 6,11-dihydro-13H-isoquino[3,2-<Emphasis Type="Italic">b</Emphasis>]quinazolin-13-one with carbonyl compounds

The reaction of 6,11-dihydro-13H-isoquino[3,2-b]quinazolin-13-one with carbonyl compounds occurs at the C₍₆₎ and/or N₍₅₎ atoms depending on the nature of the reagent and the conditions. Condensation with aldehydes gives 6-arylidene-6,11-dihydro-13H-isoquino[3,2-b]quinazolin-13-ones. Acylation using acid anhydrides or acid chlorides gave 5-acyl-, 6-acyl-, and 5,6-diacyl-5,11-dihydro-13H-isoquino[3,2-b]quinazolin-13-ones depending again on the reaction conditions. Acylation using chloroacetyl chloride is accompanied by an intramolecular alkylation to give 7H,8H-2a, 7a-diaza-cyclopenta[f,g]naphthacene-1,7(2H)-dione. Phenyl isocyanate gave the derivative containing a CONHPh group at position 6. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1509–1520, October, 2007.     

Design and synthesis of a novel class of CK2 inhibitors: application of copper- and gold-catalysed cascade reactions for fused nitrogen heterocycles

Two classes of fused nitrogen heterocycles were designed as CK2 inhibitor candidates on the basis of previous structure-activity relationship (SAR) studies. Various dipyrrolo[3,2-b:2',3'-e]pyridine and benzo[g]indazole derivatives were prepared using transition-metal-catalysed cascade and/or multicomponent reactions. Biological evaluation of these candidates revealed that benzo[g]indazole is a promising scaffold for potent CK2 inhibitors. The inhibitory activities on cell proliferation of these potent CK2 inhibitors are also presented.     

An efficient synthesis of novel pyridothieno-fused thiazolo[3,2-a]pyrimidinones via Pictet–Spengler reaction

An efficient method for the synthesis of novel pyrido[3',2':4',5']thieno[3',2':2,3]pyrido [4,5:d][1,3]thiazolo[3,2-a]pyrimidine-4-one derivatives (5) has been developed using a Pictet-Spengler reaction between 2-(3-aminothieno[2,3-b]pyridin-2-yl)thiazolo[3,2-a] pyrimidin-5-one (3), which could be obtained from the condensation of 7-(chloromethyl)-5H-thiazolo[3,2-a]pyrimidin-5-one (1) with 3-cyanopyridine-2-thione (2) via Thorpe-Ziegler isomerization, and aromatic aldehydes under NH₂SO₃H as catalysis in good yields.     

A concise synthesis of all four possible benzo[4,5]furopyridines via palladium-mediated reactions

[reaction: see text] By taking advantage of the alpha- and gamma-activation of chloropyridines as well as palladium-mediated reactions, all four possible benzo[4,5]furopyridine tricyclic heterocycles, benzo[4,5]furo[2,3-b]pyridine, benzo[4,5]furo[2,3-c]pyridine, benzo[4,5]furo[3,2-c]pyridine, and benzo[4,5]furo[3,2-b]pyridine, are efficiently synthesized from 2-chloro-3-iodopyridine, 3-chloro-4-stannylpyridine, 4-chloro-3-iodopyridine, and 2-chloro-3-hydroxypyridine, respectively.