An Efficient Synthesis of Benzo[g]thiazolo[2,3‐b]quinazolin‐4‐ium and Benzo[g]benzo[4,5]thiazolo[2,3‐b]quinazolin‐14‐ium Hydroxides by a One‐pot,Three‐component Reaction under Green Conditions

A new series of benzo[g]thiazolo[2,3‐b]quinazolin‐4‐ium and benzo[g]benzo[4,5]thiazolo[2,3‐b]quinazolin‐14‐ium hydroxide derivatives have been synthesized by the one‐pot, three‐component reaction of aryl glyoxal monohydrates, 2‐hydroxy‐1,4‐naphthoquinone, and 2‐aminothiazole or 2‐aminobenzothiazole in the presence of triethylamine and p‐toluenesulfonic acid as organocatalysts in H₂O/acetone (2:1) at room temperature. This method offers mild reaction conditions, excellent yields, easy workup, and readily accessible starting materials and catalysts.     

Direct Synthesis of Trichloro‐thiazolo[3,2‐a]pyrimidine and Thiazolo[2,3‐b]quinazoline Derivatives

An efficient one‐pot method for synthesis of new biologically active thiazolo[3,2‐a ]pyrimidine and thiazolo[2,3‐b ]quinazoline derivatives is described via reaction of pentachloropyridine with fused pyrimidine‐2(5H )‐thiones or quinazoline‐2(1H )‐thiones. These reactions were carried out in the presence of potassium carbonate as a base in acetonitrile as a solvent to produce products 3a – n in good‐to‐excellent yield. Pentachloropyridine is doubly electrophilic building blocks for the formation of ring annulated thiazolo[3,2‐a ]pyrimidine and thiazolo[2,3‐b ]quinazoline products.     

Synthesis of New Derivatives of 4‐(4,7,7‐Trimethyl‐7,8‐dihydro‐6H‐benzo[b]pyrimido[5,4‐e][1,4]thiazin‐2‐yl)morpholine

Cyclocondensation of 5‐amino‐6‐methyl‐2‐morpholinopyrimidine‐4‐thiol ( 1 ) and 2‐bromo‐5,5‐dimethylcyclohexane‐1,3‐dione ( 2 ) under mild reaction condition afforded 4,7,7‐trimethyl‐2‐morpholino‐7,8‐dihydro‐5H‐benzo[b ]pyrimido[5,4‐e ][1,4]thiazin‐9(6H )‐one ( 3 ). The ¹H and ¹³C NMR data of compound ( 3 ) are demonstrated that this compound exists primarily in the enamino ketone form. Reaction of compound ( 3 ) with phosphorous oxychloride gave 4‐(9‐chloro‐4,7,7‐trimethyl‐7,8‐dihydro‐6H‐benzo[b ]pyrimido[5,4‐e ][1,4]thiazin‐2‐yl)morpholine ( 4 ). Nucleophilic substitution of chlorine atom of compound ( 4 ) with typical secondary amines in DMF and K₂CO₃ furnished the new substituted derivatives of 4‐(4,7,7‐trimethyl‐7,8‐dihydro‐6H‐benzo[b ]pyrimido[5,4‐e ][1,4]thiazin‐2‐yl)morpholine ( 5a , 5b , 5c , 5d , 5e , 5f , 5g , 5h ). All the synthesized products were characterized and confirmed by their spectroscopic and microanalytical data.     

Five closely related 4‐chloro‐6,11‐dihydro‐5H‐benzo[b]pyrimido[5,4‐f]azepines: similar molecular structures but different supramolecular assemblies

Dibenz[b,f]azepine (DBA) is a privileged 6‐7‐6 tricyclic ring system of importance in both organic and medicinal chemistry. Benzo[b]pyrimido[5,4‐f]azepines (BPAs), which also contain a privileged 6‐7‐6 ring system, are less well investigated, probably because of a lack of straightforward and versatile methods for their synthesis. A simple and versatile synthetic approach to BPAs based on intramolecular Friedel–Crafts alkylation has been developed. A group of closely‐related benzo[b]pyrimido[5,4‐f]azepine derivatives, namely (6RS)‐4‐chloro‐6,11‐dimethyl‐6,11‐dihydro‐5H‐benzo[b]pyrimido[5,4‐f]azepine, C₁₄H₁₄ClN₃, (I), (6RS)‐4‐chloro‐8‐hydroxy‐6,11‐dimethyl‐6,11‐dihydro‐5H‐benzo[b]pyrimido[5,4‐f]azepine, C₁₄H₁₄ClN₃O, (II), (6RS)‐4‐<!?tlsb=‐0.14pt>chloro‐8‐methoxy‐6,11‐dimethyl‐6,11‐dihydro‐5H‐benzo[b]pyrimido[5,4‐f]azepine, C₁₅H₁₆ClN₃O, (III), and (6RS)‐4‐chloro‐8‐methoxy‐6,11‐dimethyl‐2‐phenyl‐6,11‐dihydro‐5H‐benzo[b]pyrimido[5,4‐f]azepine, C₂₁H₂₀ClN₃O, (IV), has been prepared and their structures compared with the recently published structure [Acosta‐Quintero et al. (2015). Eur. J. Org. Chem. pp. 5360–5369] of (6RS)‐4‐chloro‐2,6,8,11‐tetramethyl‐6,11‐dihydro‐5H‐benzo[b]pyrimido[5,4‐f]azepine, (V). All five compounds crystallize as racemic mixtures and they have very similar molecular conformations, with the azepine ring adopting a boat‐type conformation in each case, although the orientation of the methoxy substituent in each of (III) and (IV) is different. The supramolecular assemblies in (II) and (IV) depend upon hydrogen bonds of the O—H...N and C—H...π(arene) types, respectively, those in (I) and (V) depend upon π–π stacking interactions involving pairs of pyrimidine rings, and that in (III) depends upon a π–π stacking interaction involving pairs of phenyl rings. Short C—Cl...π(pyrimidine) contacts are present in (I), (II) and (IV) but not in (III) or (V).     

Three‐Component Reaction for Construction of Spiro[indoline‐3,7′‐thiazolo[3,2‐a]pyridines] and Spiro[benzo[4,5]thiazolo[3,2‐a]pyridine‐3,3′‐indolines]

The three‐component reaction of thiazole (benzothiazole), dialkyl but‐2‐ynedioate, and isatinylidene malononitriles in toluene at 110–120°C in a sealed tube afforded a mixture of cis/trans‐isomers of functionalized diastereoisomeric spiro[indoline‐3,7′‐thiazolo[3,2‐a]pyridines] and spiro[benzo[4,5]thiazolo[3,2‐a]pyridine‐3,3′‐indolines] in good yields. Both cis‐isomers and trans‐isomers were successfully separated out and fully characterized with spectroscopy and single crystal determination. Under similar conditions, the three‐component reaction containing 2‐(1,3‐dioxo‐1H‐inden‐2(3H)‐ylidene)malononitrile resulted in spiro[indene‐2,7′‐thiazolo[3,2‐a]pyridine] derivatives.     

One‐pot Combinatorial Synthesis of Benzo[4,5]imidazo‐[1,2‐a]thiopyrano[3,4‐d]pyrimidin‐4(3H)‐one Derivatives

A series of novel fused tetracyclic benzo[4,5]imidazo[1,2‐a]thiopyrano[3,4‐d]pyrimidin‐4(3H)‐one derivatives were synthesized via the reaction of aryl aldehyde, 2H‐thiopyran‐3,5(4H,6H)‐dione, and 1H‐benzo[d]imidazol‐2‐amine in glacial acetic acid. This protocol features mild reaction conditions, high yields and short reaction time.     

An Efficient Synthesis of Pyrrolo[1,2‐a] or Pyrido[1,2‐a]benzo[4,5]imidazo[1,2‐c]quinazoline Derivatives in Ionic Liquids Catalyzed by Iodine

2‐(1H ‐benzo[d ]imidazol‐2‐yl)anilines reacted with haloketones including 5‐chloropentan‐2‐one and 6‐chlorohexan‐2‐one catalyzed by iodine, giving benzo[4,5]imidazo[1,2‐c ]pyrrolo[1,2‐a ]quinazoline and 6H ‐benzo[4,5]imidazo[1,2‐c ]pyrido[1,2‐a ]quinazoline derivatives, respectively. This domino‐type reaction formed two new heterocycles and three new covalent bonds in one‐pot procedure and provided a green method for the synthesis of fused pentacyclic heterocycles bearing both quinazoline and benzimidazole moieties in ionic liquids.     

Microwave-assisted synthesis of novel N-(4-phenylthiazol-2-yl)-benzo[d]thiazole-, thiazolo[4,5-b]pyridine-, thiazolo[5,4-b]pyridine- and benzo[d]oxazole-2-carboximidamides inspired by marine topsentines and nortopsentines

We report the synthesis of novel N-(4-phenylthiazol-2-yl)-substituted benzo[d]thiazole-, thiazolo[4,5-b]pyridine-, thiazolo[5,4-b]pyridine- and benzo[d]oxazole-2-carboximidamides, which were inspired by marine topsentines and nortopsentines. Condensation of 4,5-dichloro-1,2,3-dithiazolium chloride (Appel salt) with various ortho-halogenated anilines, aminopyridines and aminophenols gave the corresponding aryliminodithiazoles in good to excellent yields. Copper(I)-mediated or nucleophilic-assisted cyclization of aryliminodithiazoles furnished cyano-functionalized benzo[d]thiazoles, thiazolo[4,5-b]- and thiazolo[5,4-b]-pyridines and benzo[d]oxazoles. The latter were condensed with substituted 4-phenylthiazol-2-amines to furnish twenty seven new polyaromatic carboximidamides in moderate to good yields.     

Efficient synthesis of pyrimido[5,4‐c]pyridazines and of thiino[2,3‐d]pyrimidines based on an aza‐wittig reaction/heterocyclization strategy

A simple one‐pot and efficient method is described for the synthesis of pyrimido[5,4‐c]pyridazines 5 and of thiino[2,3‐d] pyrimidines 15 by a domino process involving an aza‐Wittig reaction/heterocyclization. The iminophosphorane 2 reacted with phenylisocyanate, followed by heterocyclization on addition of amines to give the corresponding guanidine intermediates 4 . The guanidine intermediates were cyclized in the presence of catalytic amount of sodium ethoxide to pyrimido[5,4‐c]pyridazines 5 . Similarly, iminophosphorane 12 reacted with phenylisocyanate and amines to give thiino[2,3‐d]pyrimidines 15 in moderate yields. Furthermore, pyridazino[4,3‐d]oxazines 10 and thiino[2,3‐d]oxazines 19 were synthesized by the intremolecular aza‐Wittig reaction of phosphazenes 2 and 12 , respectively, with acid chlorides followed by heterocylization via imidoyl chloride intermediates. J. Heterocyclic Chem., (2012).     

Synthesis and properties of thiazolo[5,4-d]pyrimidine 1-oxides

Synthesis and properties of hitherto unknown thiazolo[5,4-d]pyrimidine 1-oxides are described. For example, the reaction of 6-chloro-1,3-dimethyl-5-nitrouracil (I) with methyl thioglycolate in the presence of excess triethylamine afforded 2-methoxycarbonyl-4,6-dimethylthiazolo[5,4-d]pyrimidine-5,7-(4H,6H)dione 1-oxide (IIIa), which is a versatile intermediate for the preparation of various thiazolo[5,4-d]pyrimidine derivatives.     

A convenient synthesis of novel pyrido(1′,2′:1,2)imidazo[5,4‐d]‐1,2,3‐triazinones from imidazo[1,2‐a]pyridines

The imidazo[1,2‐a]pyridine system was investigated as a synthon for the building of very attractive fused triazines, a planar, angular tri‐heterocycle with potential biological activity. Thus ethyl 3‐nitroimidazo[1,2‐a]pyridine‐2‐carboxylate was treated with ammonia or with an excess of primary amines to generate the corresponding substituted nitro carboxamidoimidazopyridines. The nitro substituent in the latter products, was reduced to yield 3‐amino‐2‐carboxamidoimidazo[1,2‐a]pyridine derivatives, which in turn were treated with nitrous acid to furnish 1‐oxo‐2‐substituted pyrido(1′,2′:1,2)imidazo[5,4‐d]‐1,2,3‐triazines.     

Synthesis and Structure–Property Relationships of 2,2′‐Bis(benzo[b]phosphole) and 2,2′‐Benzo[b]phosphole–Benzo[b]heterole Hybrid π Systems

The first comprehensive study of the synthesis and structure–property relationships of 2,2′‐bis(benzo[b]phosphole)s and 2,2′‐benzo[b]phosphole–benzo[b]heterole hybrid π systems is reported. 2‐Bromobenzo[b]phosphole P‐oxide underwent copper‐assisted homocoupling (Ullmann coupling) and palladium‐catalyzed cross‐coupling (Stille coupling) to give new classes of benzo[b]phosphole derivatives. The benzo[b]phosphole–benzo[b]thiophene and ‐indole derivatives were further converted to P,X‐bridged terphenylenes (X=S, N) by a palladium‐catalyzed oxidative cycloaddition reaction with 4‐octyne through the C_β? H activation. X‐ray analyses of three compounds showed that the benzo[b]phosphole‐benzo[b]heterole derivatives have coplanar π planes as a result of the effective conjugation through inter‐ring C? C bonds. The π–π* transition energies and redox potentials of the cis and trans isomers of bis(benzo[b]phosphole) P‐oxide are very close to each other, suggesting that their optical and electrochemical properties are little affected by the relative stereochemistry at the two phosphorus atoms. The optical properties of the benzo[b]phosphole–benzo[b]heterole hybrids are highly dependent on the benzo[b]heterole subunits. Steady‐state UV/Vis absorption/fluorescence spectroscopy, fluorescence lifetime measurements, and theoretical calculations of the non‐fused and acetylene‐fused benzo[b]phosphole–benzo[b]heterole π systems revealed that their emissive excited states consist of two different conformers in rapid equilibrium.     

Synthetic Amebicides. VIII. 7,7′-[Iminobis(alkyleneimino) [bis[benz[c] acridines] and Congeneric 9-Aminoacridines, 12-Aminobenz[a] acridines, [2-Aminobenz[b] acridines,and 4-Aminoquinolines

Thirty-five 7,7′-(iminodialkylenediimino))bis[benz[c]acridines] (VII), 7,7′-(alkylene- and phenylenediimino)bis[benz[c]acridines] (VIII and IXa-c), [iminobis(alkyleneimino)]bis[acridines, benz[a]acridines, benz[b]acridines, and quinolines] (X, Xla-c, XII, XIII, and XIVa-c), and [alkylenebis(iminoalkyleneimino)]bis[acridines, benz[c]acridines, and quinolincs] (XVI, XVII, XVIIIa and b, and XIXa-c) were synthesized by the condensation of one equivalent of the appropriate alkylenediamine with two equivalents of the requisite chloroheterocycle in phenol. Many of the bis(aminoheterocyclic) compounds are highly active against Entamoeba histolytica in vitro and in experimental animals.     

An Efficient Synthesis of Chromeno[4,3‐d]isoxazolo[5,4‐b]pyridin‐6‐one Derivatives

A series of chromeno[4,3‐d]isoxazolo[5,4‐b]pyridin‐6‐one derivatives were easily and efficiently synthesized by the reaction of 3‐acyl‐2H‐chromen‐2‐ones with isoxazol‐5‐amine in acetic acid. Some synthesized compounds were evaluated for their antiproliferative properties in vitro against cancer cells, and these compounds were found to have some activities.     

Convenient Synthesis of Spiro[benzo[d]pyrrolo[2,1‐b]thiazole‐3,2′‐indenes] Derivatives via Three‐Component Reaction

The three‐component reaction of N‐phenacylbenzothiazolium bromides, aromatic aldehydes and indane‐1,3‐dione in ethanol at room temperature in the presence of triethylamine as base afforded functionalized spiro[benzo[d]pyrrolo[2,1‐b]thiazole‐3,2′‐indenes] in good yields and with high diastereoselectivity. The ¹H NMR data and single crystal structure clearly indicated that the obtained spiro compounds predominately have one diastereoisomer.     

Synthesis of substituted pyrimido[4,5‐b] and [5,4‐c]‐[1,8]naphthyridines

Ethyl 1‐ethyl‐7‐methyl‐4‐oxo‐1,4‐dihydro[1,8]naphthyridine‐3‐carboxylate ( 1 ), precursor of nalidixic acid, has been converted in two steps through ([1,8]naphthyridin‐3‐yl)carbonylguanidine derivatives into substituted pyrimido[4,5‐b] and [5,4‐c][1,8]naphthyridines.     

Synthesis of 2‐amino‐4h‐thiazolo[5,4‐b]indole and characterization of its colored conversion products with protein tyrosine phosphatase inhibitory activity

In DMSO‐solution 2‐amino‐4H‐thiazolo[5,4‐b]indole is converted into a complex mixture of colored products. The three major conversion end‐products, of which two are inhibitors of protein tyrosine phos‐phatases (PTPs), were isolated by chromatographic methods and their structures characterized by spectro‐scopic analysis, including NMR and MS combined with computer assisted structure elucidation, and, finally, confirmed by independent chemical synthesis. Synthesis of 2‐amino‐4H‐thiazolo[5,4‐b]indole as well as its N‐acetyl derivatives prepared from either oxindole or 2‐bromo‐1‐(2‐nitro‐phenyl)ethanone is described.     

Preparation of halogenated derivatives of thiazolo[5,4‐d]thiazole via direct electrophilic aromatic substitution

Chlorination and bromination reactions of thiazolo[5,4‐d]thiazole led to the generation of its mono‐ and dihalogenated derivatives. These are the first instances of successful direct electrophilic aromatic substitution in the thiazolo[5,4‐d]thiazole ring system. X‐ray analysis demonstrates that both 2‐bromothiazolo[5,4‐d]‐thiazole and 2,5‐dibromothiazolo[5,4‐d]thiazole are planar structures, with strongly manifested π‐stacking in the solid state. Theoretical analysis of the pyridine‐catalyzed halogenation (MP2/6‐31+G(d) and B3LYP/6‐31+G(d) calculations) reveals that introduction of one halogen actually leads to a slightly enhanced reactivity towards further halogenation. Several halogenation mechanisms have been investigated: 1) The direct C‐halogenation with N‐halopyridine as electrophile; 2) C‐halogenation via intermediate N‐halogenation, and 3) C‐halogenation following an addition ‐ elimination pathway, with intermediate formation of a cyclic halonium ion. The theoretical studies suggest that the direct C‐halogenation is the favored mechanism.     

Heteroarene‐fused π‐conjugated main‐chain polymers containing 4,7‐bis(4‐octylthiophen‐2‐yl)benzo[c][1,2,5]thiadiazole or 2,5‐bis(4‐octylthiophen‐2‐yl)thiazolo[5,4‐d]thiazole and their application to photovoltaic devices

Two conjugated main‐chain polymers consisting of heteroarene‐fused π‐conjuagted donor moiety alternating with 4,7‐bis(5‐bromo‐4‐octylthiophen‐2‐yl)benzo[c][1,2,5]thiadiazole (P1) or 2,5‐bis(5‐bromo‐4‐octylthiophen‐2‐yl) thiazolo[5,4‐d]thiazole (P2) units have been synthesized. They are intrinsically amorphous in nature and do not exhibit crystalline melting temperatures during thermal analysis. The effect of the fused rings on the thermal, optical, electrochemical, charge transport, and photovoltaic properties of these polymers has been investigated. The polymer (P1) containing 4,7‐bis(5‐bromo‐4‐octylthiophen‐2‐yl)benzo[c][1,2,5] thiadiazole has a broad absorption extending from 300 to 600 nm with optical bandgaps as low as 2.02 eV. The HOMO levels (5.42 to 5.29 eV) are more sensitive to the choice of acceptor. The polymers were employed to fabricate organic photovoltaic cells with methanofullerene [6,6]‐phenyl C71‐butyric acid methyl ester (PC₇₁BM). As a result, the polymer solar cell device containing P1 had the best preliminary results with an open‐circuit voltage of 0.61 V, a short‐circuit current density of 6.19 mA/cm², and a fill factor of 0.32, offering an overall power conversion efficiency of 1.21%. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2010     

On the chemistry of 5‐aryl‐2‐hydrazino‐benzo[6,7]cyclohepta[1,2‐b]pyrido[2,3‐e] pyrimidin‐4‐one

Several pyrido[2,3‐e]pyrimidine fused with other rings have been prepared by intramolecular cyclization of 5‐(4‐chlorophenyl)‐2‐hydrazino‐benzo [6,7]cyclohepta‐[1,2‐b]pyrido[2,3‐e]pyrimidine‐4‐one ( 1 ) with acids, carbon disulfide to form triazole derivatives ( 2,4 ), halo‐ketones to give triazine derivative ( 5 ), β‐ketoesters, β‐cyanoesters, and β‐diketones to yield 2‐(1‐pyrazolyl) derivatives ( 7,9,10 ), and aldehydes to form arylhydrazone derivatives ( 11a,b ) which cyclized to form triazoles ( 12a,b ). Also, acyclic N‐nucleosides are prepared by heating under reflux 2‐hydrazino‐benzo[6,7]cyclohepta[1,2‐b]pyrido[2,3‐e] pyrimidin‐4‐one ( 1 ) with xylose and glucose to give the corresponding acyclic N‐nucleosides ( 13a,b ) which are cyclized to afford the corresponding protected tetra and penta–O‐acetate C‐nucleosides ( 14a,b ). Deacetylating of the latter nucleosides afforded the free acyclic C‐nucleosides ( 15a,b ). © 2007 Wiley Periodicals, Inc. Heteroatom Chem 18:34–43, 2007; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20248