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.     

Synthesis of 1,2,3,12a,12b‐Hexahydrocyclopropa‐[1,2‐d]benzo[f]pyrrolo[1,2‐b]isoquinolin‐5,7‐dione related to duocarmycins and anthramycin

Structural features of the Duocarmycins and Anthramycin were incorporated into 1,2,3,12a,12b‐hexahydro‐cyclopropa[1,2‐d]benzo[f]pyrrolo[1,2‐b]isoquinolin 5,7‐dione. The synthesis of the cis and trans diastereomers was accomplished using a benzyne Diels‐Alder reaction and an imine‐anhydride cyclization as key steps.     

Efficient New Synthesis of N‐Arylbenzo[b]furo[3,2‐d]pyrimidin‐4‐amines and Their Benzo[b]thieno[3,2‐d]pyrimidin‐4‐amine Analogues via a Microwave‐Assisted Dimroth Rearrangement

A useful and rapid access to libraries of N‐arylbenzo[b]furo[3,2‐d]pyrimidin‐4‐amines ( 1 ) and their novel benzo[b]thieno[3,2‐d]pyrimidin‐4‐amine analogues ( 2 ) was investigated for the first time. Title compounds were obtained via microwave‐accelerated condensation and Dimroth rearrangement of suitable anilines with N′‐(2‐cyanaryl)‐N,N‐dimethylformimidamides obtained by reaction of benzo[b]furane and benzo[b]thiophene precursors with N,N‐dimethylformamide dimethyl acetal. This work also demonstrates that well‐controlled parameters offer comfortable use of microwave technology and are both safe and beneficial to the environment. Some products obtained in this article exhibit interesting in vitro antiproliferative effects.     

Synthesis of Pyrido[2′,3′: 3,4]pyrazolo[1,5‐a]pyrimidine,Pyrido[2′,3′:3,4]pyrazolo[5,1‐c][1,2,4]triazine,and Pyrazolyl Oxadiazolylthieno[2,3‐b]pyridine Derivatives

6‐(2‐Thienyl)‐4‐(trifluoromethyl)‐1H‐pyrazolo[3,4‐b]pyridine‐3‐amine reacted with different active methylene compounds to afford pyridopyrazolopyrimidine derivatives. On the other hand, it reacted with some halo compounds to give the imidazo[1′,2′:1,5]pyrazolo[3,4‐b]pyridine derivatives. Also, it diazotized to give the corresponding diazonium chloride that is coupled with several active methylene compounds to give the corresponding triazine derivatives. Furthermore, compound 3‐amino‐6‐(2(thienyl)‐4‐(trifluoromethyl)thieno[2,3‐b]pyridine‐2‐carbohydrazide reacted with some β‐dicarbonyl compounds and some sulfur‐containing compounds to afford the corresponding pyrazolyl oxadiazolylthieno[2,3‐b]pyridine derivatives.     

New Synthetic Approach to Naphtho[1,2‐b]furan and 4′‐Oxo‐Substituted Spiro[cyclopropane‐1,1′(4′H)‐naphthalene] Derivatives

A one‐step synthesis of ethyl 2,3‐dihydronaphtho[1,2‐b]furan‐2‐carboxylate and/or ethyl 4′‐oxospiro[cyclopropane‐1,1′(4′H)‐naphthalene]‐2′‐carboxylate derivatives 2 and 3 , respectively, from substituted naphthalen‐1‐ols and ethyl 2,3‐dibromopropanoate is described (Scheme 1). Compounds 2 were easily aromatized (Scheme 2). In the same way, 3,4‐dibromobutan‐2‐one afforded the corresponding 1‐(2,3‐dihydronaphtho[1,2‐b]furan‐2‐yl)ethanone and/or spiro derivatives 8 and 9 , respectively (Scheme 6). A mechanism for the formation of the dihydronaphtho[1,2‐b]furan ring and of the spiro compounds 3 is proposed (Schemes 3 and 4). The structures of spiro compounds 3a and 3f were established by X‐ray structural analysis. The reactivity of compound 3a was also briefly examined (Scheme 9).     

Aktivierte Chinone: regiospezifische Synthesen von substituierten Dibenzo [b,d]pyran-6-onen und Benzo [b]naphtho [d]pyran-6-onen

Activated Quinones: Regiospecific Syntheses of Substituted Dibenzo [b, d]pyran-6-ones and Benzo[b]naphtho [d]pyran-6-ones The reaction of 2-methoxycarbonyl-1, 4-benzoquinone (1) with substituted phenols leads in an acid-catalyzed, regiospecific way to substituted dibenzo [b, d]-pyran-6-ones (compounds 3 and 6 ). The cycloaddition of 1,3-butadiene to the latter yields compounds 7. Tautomerisation of 7 and oxidation gives the benzo[b]-naphtho[d]pyran-6-ones 8 and 10 , respectively.     

Synthesis of 4-methylfuro[3′,2′:5,6]benzofuro[3,2-c]pyridine

4-Methylfuro[3′,2′:5,6]benzofuro[3,2-c]pyridine ( 3 ) was synthetized from 2-acetylfuro[3,2-f]benzo[b]furan ( 4 ) or from 2-acetyl-5,6-dihydrofuro[3,2-f]benzo[b]furan ( 10 ). The key step involves a rearrangement-cyclization of azides 6 and 12 to form 4-methylfuro[3′,2′:5,6]benzofuro[3,2-c]pyridin-1(2H) one ( 7 ) and 8,9-dihydro-4-methylfuro[3′,2′:5,6]benzofuro[3,2c]pyridin-1(2H)-one ( 13 ). Introduction of an aminoalkyl chain on carbon 1 was effected by substitution of 1-chloro-4-methylfuro[3′,2′:5,6]benzofuro[3,2-c]pyridine ( 8 ).     

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).     

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.     

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.     

Polycyclic arene sulfides. Preparation of 1a,2,3,11b-tetrahydrobenz-[5,6]anthra[1,2-b]thiirene, 6b,7a,8,9-tetrahydrobenzo[10,11]-chryseno[1,2-b]thiirene,and 7,8,8a,9a-tetrahydrobenzo-[10,11]chryseno[3,4-b]thiirene

The title compounds 5, 7 and 9 which are the first arene sulfides of 7,8-dihydrobenz[a]anthracene, 8,9-and 10,11-dihydrobenzo[a]pyrene, respectively, have been synthesized by treatment of the corresponding arene oxides 4, 6 and 8 with N,N-dimethylthioformamide in the presence of catalytic amounts of trifluoroacetic acid.     

The synthesis of novel polycyclic heterocyclic ring systems via photocyclization. 22 Dibenzo[f,h]benzothieno[2,3‐c]quinoline,dibenzo[f,h]benzothieno[2,3‐c][1,2,4]triazolo[4,3‐a]quinoline and dibenzo[f,h]naphtho[2′,1′:4,5]thieno[2,3‐c]quinoline

Photocyclization of 3‐chloro‐N‐(9‐phenanthryl)benzo[b]‐thiophene‐2‐carboxamide ( 3 ) and 3‐chloro‐N‐(9‐phenanthryl)‐naphtho[1,2‐b]thiophene‐2‐carboxamide ( 10 ) yielded dibenzo[f,h]benzothieno[2,3‐c]‐quinolin‐10(9H)‐one ( 4 ) and dibenzo[f,h]naphtho[2′,1′:4,5]thieno[2,3‐c]quinolin‐10(9H)‐one ( 11 ), respectively. Further elaboration of the lactams provided three novel unsubstituted new ring systems.     

Synthesis and reactions of 11H‐benzo[b]pyrano[3,2‐f]indolizines an pyrrolo[3,2,1‐ij]pyrano[3,2‐c]quinolines

2‐Methyl‐3H‐indoles 1 cyclize with two equivalents of ethyl malonate 2 to form 4‐hydroxy‐11H‐benzo[b]pyrano[3,2‐f]indolizin‐2,5‐diones 3, whereas 2‐mefhyl‐2,3‐dihydro‐1H‐indoles 9 give under similar conditions regioisomer 8‐hydroxy‐5‐methyl‐4,5‐dihydro‐pyrrolo[3,2,1‐ij]pyrano[3,2‐c]quinolin‐7,10‐diones 10 . The pyrone rings of 3 and 9 can be cleaved either by alkaline hydrolysis to give 7‐acetyl‐8‐hydroxy‐10H‐pyrido[1,2‐a]indol‐6‐ones 4 or 5‐acetyl‐6‐hydroxy‐2‐methyl‐1,2‐dihydro‐4H‐pyrrolo‐[3,2,1‐ij]quinolin‐4‐ones 11 , respectively. Chlorination of 3 and 9 with sulfurylchloride gives under subsequent ring opening 7‐dichloroacetyl‐8‐hydroxy‐10H‐pyrido[1,2‐a]indol‐6‐ones 5 or 5‐dichloracetyl‐6‐hydroxy‐2‐methyl‐1,2‐dihydro‐4H‐pyrrolo[3,2,1‐ij]quinolin‐4‐ones 12 . The dichloroacetyl group of 5 can be reduced with zinc to 7‐acetyl‐8‐hydroxy‐10H‐pyrido[1,2‐a]indol‐6‐ones 7. Treatment of the acetyl compounds 4, 7 and 11 with 90% sulfuric acid cleaves the acetyl group and yields 8‐hydroxy‐10H‐pyrido[1,2‐a]‐indol‐6‐ones 6 and 8 , and 6‐hydroxy‐2‐methyl‐1,2‐dihydro‐4H‐pyrrolo[3,2,1‐ij]quinolin‐4‐ones 13 . Reaction of dichloroacetyl compounds 12 with sodium azide yields 6‐hydroxy‐2‐methyl‐5‐(1H‐tetrazol‐5‐ylcarbonyl)‐1,2‐dihydro‐4H‐pyrrolo[3,2,1‐ij]quinolin‐4‐ones 14 via intermediate geminal diazides.     

Strategy to Construct Stair‐Shaped Partially Reduced Naphtho[1,2‐b]pyrano[2,3‐d]oxepines and Dinaphtho[1,2‐b,d]oxepines

A concise and efficient base‐induced synthesis of stair‐shaped, 4‐methylthio‐2‐oxo‐5,6‐dihydro‐2H‐naphtho[1,2‐b]pyran[2,3‐d]oxepine‐3‐carbonitriles ( 3 ) has been delineated by the reaction of 3,4‐dihydronaphtho[1,2‐b]oxepin‐5(2H)‐one ( 1 ) and methyl 2‐cyano‐3,3‐dimethylthioacrylate in DMSO using powdered KOH as a base at room temperature. Amination of 3 has been achieved by reaction with secondary amine in ethanol at reflux temperature to yield 4‐sec‐amino‐2‐oxo‐5,6‐dihydro‐2H‐naphtho[1,2‐b]pyran[2,3‐d]oxepine‐3‐carbonitriles ( 4 ). Reaction of 3 with aryl methyl ketone ( 5 ) in DMSO at room temperature using powdered KOH as a base produced stair‐shaped 5‐aryl‐7,8‐dihydro‐1,4‐dioxa‐2,3‐dioxodinaphtho[1,2‐b,d]oxepine ( 6 ) in good yields. However, reaction of 6‐aryl‐2H‐pyran‐2‐one‐3‐carbonitrile ( 8 ) with 3,4‐dihydronaphtho[1,2‐b]oxepin‐5(2H)‐one ( 1 ) did not give similar product, but in lieu 4‐aryl‐5,6‐dihydronaphtho[1,2‐b]oxepino[4,5‐b]pyran‐2‐ylidene)acetonitrile ( 9 ) was isolated and characterized.     

Synthesis of novel pyrido[3′,2′:4,5]thieno[3,2‐d]pyrimidines,pyrido[3″,2″:4′,5′]thieno[3′,2′:4,5]pyrimido[l,6‐a]benzimidazoles and related fused systems

3‐Amino‐4‐aryl‐5‐ethoxycarbonyl‐6‐methylthieno[2,3‐b]pyridine‐2‐carboxamides 3a‐c were prepared from ethyl 4‐aryl‐3‐cyano‐6‐methyl‐2‐thioxo‐1,2‐dihydropyridine‐5‐carbonylates 1a‐c and reacted with some carbonyl compounds to give tetrahydropyridothienopyrimidine derivatives 6a‐c, 7a‐c and 8a‐c , respectively. Treatment of compound 3c with chloroacetyl chloride led to the formation of a next key compound, ethyl 2‐chloromethyl‐4‐oxo‐3,4‐dihydropyrido[3′,2′:4,5]thieno[3,2‐d]pyrimidine‐8‐carboxylate 9 . Also, 3‐amino‐2‐benzimidazolylthieno[2,3‐b]pyridine‐5‐carboxylate 5 and 2‐(3′‐aminothieno [2,3‐b]pyridin‐2′‐yl)‐4‐oxo‐3,4‐dihydropyrido[3′,2′:4,5]thieno[3,2‐d]pyrimidine‐8‐carboxylate 17 were prepared from 1c. The compounds 5, 9 and 17 were used as good synthons for other pyridothienopyrimidines and pyridothienopyrimidobenzimidazoles as well as for related fused polyheterocyclic systems.     

Synthesis of spiro[2H-indole-2,1′-1H-isoindole]-3,3′-diones,spiro[1H-isobenzofuran-1,2′-2H-indole]-3,3′-diones and spiro[benzofuran-2,1′-isobenzofuran]-3,3′-diones via transannular reactions of eight membered ring intermediates

An auto oxidation-rearrangement product 4 was isolated from a high dilution reaction of ninhydrin with 3,4,5-trimethoxyaniline in water. A general synthesis of this compound and its derivatives 4–6 was devised by oxidation of tetrahydroindeno[1,2-b]indol-10-ones 1–3 with sodium periodate to give isoindolo[2,1-a]-indole-6,11-diones 4–6 in good yield. Compounds 4–6 can be easily transformed into spiro[1H-isobenzofuran-1,2′-2H-indole]-3,3′-diones 8–10 , spiro[2H-indole-2,1′-1H-isoindole]-3,3′-diones 11–13 and isoindole[1,2-a:2′,1′-b]pyrimidine-5,15-diones 15, 16 in high yields. Analogous reactions were performed on 3-amino-5a, 10a-dihydroxybenzo[b]indeno[2,1-d]furan-10-one ( 17 ) to give a dibenzoxocintrione 18 , spiro-[benzofuran-2,1′-isobenzofuran]-3,3′-dione 19 and an isoindol-1-one 20 .     

Synthesis of pyrazolo[1,5‐a]‐, 1,2,4‐triazolo[1,5‐a]‐ and imidazo[1,2‐a]pyrimidines related to zaleplon,a new drug for the treatment of insomnia

This paper describes the preparation of some pyrazolo[1,5‐a]‐, 1,2,4‐triazolo[1,5‐a]‐ and imidazo[1,2‐a]‐pyrimidines substituted on the pyrimidine moiety by a 4‐[(N‐acetyl‐N‐ethyl)amino]phenyl group. A new synthesis of related benzo[h]pyrazolo[1,5‐a]‐, benzo[h]pyrazolo[5,1‐b]‐ and benzo[h]1,2,4‐triazolo[1,5‐a]‐quinazolines is also reported.     

Quinolone analogues 6 [1‐5]. Synthesis of 3‐halogeno‐1‐methylpyridazino[3,4‐b]quinoxalin‐4(1H)‐ones

The reaction of the quinoxaline N‐oxides 7a,b with diethyl ethoxymethylenemalonate gave the 1‐methylpyridazino[3,4‐b]quinoxaline‐4,4‐dicarboxylates 8a,b , whose reaction with N‐bromosuccinimide or N‐chlorosuccinimide afforded the 3‐halogeno‐1‐methylpyridazino[3,4‐b]quinoxaline‐4,4‐dicarboxylates 9a‐d. The reaction of compounds 9a‐d with hydrazine hydrate resulted in hydrolysis and decarboxylation to provide the 3‐halogeno‐1‐methylpyridazino[3,4‐b]quinoxaline‐4‐carboxylates 10a‐d , whose reaction with nitrous acid effected oxidation to furnish the 3‐halogeno‐4‐hydroxy‐1‐methylpyridazino[3,4‐b]quinoxaline‐4‐carboxylates 11a‐d , respectively. The reaction of compounds 11a‐d with hydrazine hydrate afforded the 3‐halogeno‐1‐methylpyridazino[3,4‐b]quinoxalin‐4‐ols 12a‐d , whose oxidation provided the 3‐halogeno‐1‐methylpyridazino[3,4‐b]quinoxalin‐4(1H)‐ones 6a‐d , respectively. Compounds 6a‐d had antifungal activities in vitro.     

Synthesis of Imidazo[1,2‐a]pyridines and Imidazo[2,1‐b]thiazoles Attached to a Cycloalkyl or Saturated Heterocycle Containing a Tertiary Hydroxy Substitution

A new method has been developed for the synthesis of imidazo[1,2‐a]pyridines, imidazo[2,1‐b]thiazoles, and benzo[d]imidazo[2,1‐b]thiazoles attached to a cycloalkyl or saturated heterocycle containing a tertiary hydroxy substitution. Readily available substituted 2‐aminopyridines, 2‐aminothiazoles, and 2‐aminobenzothiazoles were treated with bromohydroxycycloalkyl ethanones to afford the desired products in good yields.     

Benzo[1,2‐b:4,5‐b′]dithiophene Building Block for the Synthesis of Semiconducting Polymers

This review covers the synthesis and polymerization of benzo[1,2‐b: 4,5‐b′]dithiophene (BDT) to generate semiconducting polymers used in organic field‐effect transistors (OFET) and organic solar cells applications.