Microwave‐assisted synthesis of new regioisomeric 6,7‐dihydroindeno[1,2‐e]pyrimido[4,5‐b][1,4]diazepin‐5(5aH)‐ones

Novel 11‐amino‐6‐aryl‐6,7‐dihydroindeno[1,2‐e] pyrimido[4,5‐b][1,4]diazepin‐5(5aH)‐ones 4a‐f were prepared regioselectively by the tricomponent reaction of 4,5,6‐triaminopyrimidine 1, 1,3‐indandione 2 and aromatic aldehydes 3a‐f. The bicomponent approach, using 2,4,5,6‐tetraaminopyrimidine 5 and 2‐aryl‐ideneindandiones 6a‐f as reagents, afforded 9,11‐diamino‐6‐aryl‐6,7‐dihydroindeno[1,2‐e]pyrimido[4,5‐b]‐[1,4]diazepin‐5(5aH)‐ones 7a‐f in good yields and the regioisomeric 8,10‐diamino derivatives 8a‐c in lower yields. Both, bi‐ and tricomponent approaches were performed by microwave irradiation and all products were fully characterized by detailed NMR measurements.     

FeCl3‐Mediated Oxidative Spirocyclization of Difluorenylidene Diarylethanes Leading to Dispiro[fluorene‐9,5′‐indeno[2,1‐a]indene‐10′,9′′‐fluorene]s

A novel FeCl₃‐mediated oxidative spirocyclization for construction of a new class of di‐spirolinked π‐conjugated molecules, dispiro[fluorene‐9,5′‐indeno[2,1‐a]indene‐10′,9′′‐fluorene]s (DSFIIFs), has been reported. The combination of FeCl₃ with FeO(OH) triggered an unprecedented double one‐electron oxidation of difluorenylidene diarylethanes to afford the corresponding dispirocycles in high yields. The highest fluorescence quantum yield was up to 0.94 in solution. This protocol is also applicable to the synthesis of the non‐spirolinked dihydroindenoindenes.     

Synthesis of the Unknown Indeno[1,2‐a]fluorene Regioisomer: Crystallographic Characterization of Its Dianion

Of the five possible indenofluorene regioisomers, examples of a fully conjugated indeno[1,2‐a ]fluorene scaffold have so far remained elusive. This work reports the preparation and characterization of 7,12‐dimesitylindeno[1,2‐a ]fluorene as a highly reactive species. Experimental and computational data support the notion of a molecule with pronounced diradical character that exists in a triplet ground state. As such, both NICS and ACID calculations suggest that the indeno[1,2‐a ]fluorene scaffold is weakly Baird aromatic. Reduction of the unstable red solid with Cs metal produces the dianion of the title compound, from which single crystals could be obtained and X‐ray data acquired, thus fully corroborating the proposed indeno[1,2‐a ]fluorene hydrocarbon core.     

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.     

ortho‐, meta‐, and para‐Dihydroindenofluorene Derivatives as Host Materials for Phosphorescent OLEDs

This work reports the first structure–properties relationship study of ortho [2,1‐c]‐, meta [1,2‐a]‐, and para [1,2‐b]dihydroindenofluorenes, highlighting the influence of bridge rigidification on the electronic properties. This study has made it possible to devise an extended π‐conjugated molecule with both a high triplet state energy level and excellent thermal and morphological stability. As a proof of concept, dihydroindenofluorenes were used as the host in sky‐blue phosphorescent organic light‐emitting diodes (PhOLEDs) w ith high performance.     

Synthesis of [1,2‐a] benzimidazolo‐1,3,5‐triazin‐2‐thione, [1,2‐a] benzimidazolo‐1,3,5‐thiadiazin‐2‐thione, [1,2‐a] benzimidazolo‐1,3,5‐triazin‐2‐amine,and [1,2‐a] benzimidazol‐2‐yl amidrazone

N‐benzimidazol‐2‐yl imidate type 1 reacts with thiourea, carbon disulfide, cyanamide, and hydrazide to give, respectively, [1,2‐a] benzimidazolo‐1,3,5‐triazin‐2‐thione 2 , [1,2‐a] benzimidazolo‐1,3,5‐thiadiazin‐2‐thione 3 , [1,2‐a] benzimidazolo‐1,3,5‐triazin‐2‐amine 4 , and [1,2‐a] benzimidazol‐2‐yl amidrazone 5 with good yields. Structures elucidation of all newly synthesized heterocyclic compounds was based on the data of IR, ¹H NMR, ¹³C NMR, elemental analysis, and MS of some products. © 2010 Wiley Periodicals, Inc. Heteroatom Chem 21:279–283, 2010; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20618     

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.     

One pot synthesis of substituted dihydroindeno[1,2‐b]indoles and dihydrobenzo[a]carbazoles by photostimulated reactions of o‐iodoaniline with carbanions by the SRN1 mechanism

The photostimulated reaction of enolate anions of cyclic aromatic ketones such as substituted indan‐1‐ones and 3,4‐dihydro‐2H‐naphthalen‐1‐one with o‐iodoaniline in DMSO affords 1‐, 2‐, 3‐, and 4‐methoxy‐5,10‐dihydroindeno[1,2‐b]indoles (34‐40%), 1,2‐, 1,4‐, and 2,3‐dimethoxy‐5,10‐dihydroindeno[1,2‐b]‐indoles (31‐43%), and 1‐, 2‐, and 3‐methoxy‐5,11‐dihydro‐6H‐benzo[a]carbazoles (42‐61%) by the S_RN1 mechanism in one pot reactions.     

A New Four‐Component Reaction for the Synthesis of Spiro[4H‐indeno[1,2‐b]pyridine‐4,3′‐[3H]indoles]

A new four‐component synthesis of spiro[4H‐indeno[1,2‐b]pyridine‐4,3′‐[3H]indoles] and spiro[acenaphthylene‐1(2H),4′‐[4H‐indeno[1,2‐b]pyridines] by the reaction of indane‐1,3‐dione, 1,3‐dicarbonyl compounds, isatins (=1H‐indole‐2,3‐diones) or acenaphthylene‐1,2‐dione, and AcONH₄ in refluxing toluene in the presence of a catalytic amount of pyridine is reported.     

Modulation of the Physicochemical Properties of Donor–Spiro–Acceptor Derivatives through Donor Unit Planarisation: Phenylacridine versus Indoloacridine—New Hosts for Green and Blue Phosphorescent Organic Light‐Emitting Diodes (PhOLEDs)

This work reports a detailed structure–property relationship study of a series of efficient host materials based on the donor–spiro–acceptor (D‐spiro‐A) design for green and sky‐blue phosphorescent organic light‐emitting diodes (PhOLEDs). The electronic and physical effects of the indoloacridine (IA) fragment connected through a spiro bridge to different acceptor units, namely, fluorene, dioxothioxanthene or diazafluorene moiety, have been investigated in depth. The resulting host materials have been easily synthesised through short, efficient, low‐cost, and highly adaptable synthetic routes by using common intermediates. The dyes possess a very high triplet energy (E_T) and tuneable HOMO/LUMO levels, depending on the strength of the donor/acceptor combination. The peculiar electrochemical and optical properties of the IA moiety have been investigated though a fine comparison with their phenylacridine counterparts to study the influence of planarisation. Finally, these molecules have been incorporated as hosts in green and sky‐blue PhOLEDs. For the derivative SIA‐TXO₂ as a host, external quantum efficiencies as high as 23 and 14 % have been obtained for green and sky‐blue PhOLEDs, respectively.     

Pd‐Catalyzed Cyclocarbonylation of 2‐(2‐Bromoaryl)indoles with CO as a C1 Source: Selective Access to 6 H‐Isoindolo[2,1‐a]indol‐6‐ones and Indeno[1,2‐b]indol‐10(5 H)‐ones

A highly efficient and regioselective synthetic route to 6 H‐isoindolo[2,1‐a]indol‐6‐ones and indeno[1,2‐b]indol‐10(5 H)‐ones through the Pd‐catalyzed cyclocarbonylation of 2‐(2‐bromoaryl)indoles under atmospheric CO pressure has been achieved. Notably, the regioselectivity of the reaction was exclusively dependent on the structural characteristics of the indole substrates. With N‐unsubstituted indoles as the starting materials, the reaction afforded 6H‐isoindolo[2,1‐a]indol‐6‐ones in good‐to‐excellent yields. On the other hand, with N‐substituted indoles as the substrates, the reaction gave indeno[1,2‐b]indol‐10(5 H)‐ones in a highly regioselective manner.     

Microwave‐assisted nucleophilic cleavage of 5,7‐dimethyl‐2‐phenyl‐1‐oxo‐lH‐pyrazolo[ 1,2‐a]pyrazol‐4‐ylium‐3‐olate to α‐phenylmalonamides

Three α‐phenylmalonamides have been prepared by the selective nucleophilic cleavage of 5,7‐dimethyl‐2‐phenyl‐1‐oxo‐1H‐pyrazolo[1,2‐a]pyrazol‐4‐ylium‐3‐olate in solventless microwave syntheses. The three weak nucleophiles employed were aniline, p‐chloroaniline and m‐toluidine. The α‐phenylmalonamides of these three aniline derivatives could not be prepared using the previously reported solvent syntheses via 3‐oxopyrazolo[1,2‐a]pyrazol‐8‐ylium‐1‐olates. All products were characterised using, infrared spectroscopy, ¹H nmr and electrospray mass spectrometry. The single crystal X‐ray structures of the starting pyrazolo‐[1,2‐a]pyrazole and α‐phenylmalon‐m‐toluidide are also reported.     

Synthesis and reactions of 10,10‐dimethyl‐10H‐pyrido[1,2‐a]indol‐6‐ones

Cyclocondensation of 2,3,3‐trimefhyl‐3H‐indoles 2 with malonates 3 gives 8‐hydroxy‐10,10‐dimefhyl‐10H‐pyrido[1,2‐a]indol‐6‐ones 4 , which were halogenated in position 7, 8 and 9 with sulfuryl chloride, bromine or phosphoroxychloride to give the corresponding halo‐10,10‐dimethyl‐10H‐pyrido[1,2‐a]indoles 5, 6, 7 and 8 . Amination affords the 8‐amino‐10,10‐dimethyl‐10H‐pyrido[1,2‐a]indol‐6‐one 9 . Nitration gives either the 10,10‐dimethyl‐7‐nitro‐10H‐pyrido[1,2‐a]indoles 10 or 10,10‐dimethyl‐7‐hydroxy‐10H‐pyrido[1,2‐a]indoles 11 , depending on the conditions.     

One‐pot Sequential Reactions Featuring a Copper‐catalyzed Amination Leading to Pyrido[2′,1′:2,3]imidazo[4,5‐c]quinolines and Dihydropyrido[2′,1′:2,3]imidazo[4,5‐c]quinolines

Tetracyclic skeletons combining an imidazo[1,2‐a]pyridine moiety with a quinoline framework such as pyrido[2′,1′:2,3]imidazo[4,5‐b]quinoline are stimulating increasing interests since they are close isosteres of a series of powerful antiproliferative compounds. In this paper, we report a novel methodology for the synthesis of pyrido[2′,1′:2,3]imidazo[4,5‐c]quinolines through one‐pot sequential reactions of commercially available or readily obtainable 2‐aminopyridines, 2‐bromophenacyl bromides, aqueous ammonia, and aldehydes. Moreover, dihydropyrido[2′,1′:2,3]imidazo[4,5‐c]quinolines could also be obtained in a similar manner by using various ketones as the substrates in place of aldehydes. Notably, the whole procedure combines condensation/amination/cyclization reactions in one pot to give complex compounds in a simple and practical manner. Compared with literature methods, the synthetic strategy reported herein has the advantages of readily available starting materials, structural diversity of products, good functional group tolerance, and obviation of step‐by‐step operations.     

A versatile synthesis of 4,5‐dihydropyrrolo[1,2‐a]quinoxalines

The reaction of 1‐(2‐aminophenyl)pyrrole with aromatic or heteroaromatic aldehydes in ethanol and catalytic amounts of acetic acid leads to 4,5‐dihydropyrrolo[1,2‐a]quinoxalines in high yields. When aliphatic aldehydes were used under the same conditions, a slow oxidation to the corresponding pyrrolo[1,2‐a]quinoxalines can occur; the oxidation can be avoided by preparing in situ the 5‐acetyl derivatives of the 4,5‐dihydropyrrolo[1,2‐a]quinoxalines.     

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.     

Benzo[a]heptalenes from Heptaleno[1,2‐c]furans. Part 2

It is shown in this ‘Part 2’ that heptaleno[1,2‐c]furans 1 react thermally in a Diels–Alder‐type [4+2] cycloaddition at the furan ring with vinylene carbonate (VC), phenylsulfonylallene (PSA), α‐(acetyloxy)acrylonitrile (AAN), and (1Z)‐1,2‐bis(phenylsulfonyl)ethene (ZSE) to yield the corresponding 1,4‐epoxybenzo[d]heptalenes (cf. Schemes 1, 5, 6, and 8). The thermal reaction of 1a and 1b with VC at 130° and 150°, respectively, leads mainly to the 2,3‐endo‐cyclocarbonates 2,3‐endo‐ 2a and ‐ 2b and in minor amounts to the 2,3‐exo‐cyclocarbonates 2,3‐exo‐ 2a and ‐ 2b . In some cases, the (P*)‐ and (M*)‐configured epimers were isolated and characterized (Scheme 1). Base‐catalyzed cleavage of 2,3‐endo‐ 2 gave the corresponding 2,3‐diols 3 , which were further transformed via reductive cleavage of their dimesylates 4 into the benzo[a]heptalenes 5a and 5b , respectively (Scheme 2). In another reaction sequence, the 2,3‐diols 3 were converted into their cyclic carbonothioates 6 , which on treatment with (EtO)₃P gave the deoxygenated 1,4‐dihydro‐1,4‐epoxybenzo[d]heptalenes 7 . These were rearranged by acid catalysis into the benzo[a]heptalen‐4‐ols 8a and 8b , respectively (Scheme 2). Cyclocarbonate 2,3‐endo‐ 2b reacted with lithium diisopropylamide (LDA) at ?70° under regioselective ring opening to the 3‐hydroxy‐substituted benzo[d]heptalen‐2‐yl carbamate 2,3‐endo‐ 9b (Scheme 3). The latter was O‐methylated to 2,3‐endo‐(P*)‐ 10b . The further way, to get finally the benzo[a]heptalene 13b with MeO groups in 1,2,3‐position, could not be realized due to the fact that we found no way to cleave the carbamate group of 2,3‐endo‐(P*)‐ 10b without touching its 1,4‐epoxy bridge (Scheme 3). The reaction of 1a with PSA in toluene at 120° was successful, in a way that we found regioisomeric as well as epimeric cycloadducts (Scheme 5). Unfortunately, the attempts to rearrange the products under strong‐base catalysis as it had been shown successfully with other furan–PSA adducts were unsuccessful (Scheme 4). The thermal cycloaddition reaction of 1a and 1b with AAN yielded again regioisomeric and epimeric adducts, which could easily be transformed into the corresponding 2‐ and 3‐oxo products (Scheme 6). Only the latter ones could be rearranged with Ac₂O/H₂SO₄ into the corresponding benzo[a]heptalene‐3,4‐diol diacetates 20a and 20b , respectively, or with trimethylsilyl trifluoromethanesulfonate (TfOSiMe₃/Et₃N), followed by treatment with NH₄Cl/H₂O, into the corresponding benzo[a]heptalen‐3,4‐diols 21a and 21b (Scheme 7). The thermal cycloaddition reaction of 1 with ZSE in toluene gave the cycloadducts 2,3‐exo‐ 22a and ‐ 22b as well as 2‐exo,3‐endo‐ 22c in high yields (Scheme 8). All three adducts eliminated, by treatment with base, benzenesulfinic acid and yielded the corresponding 3‐(phenylsulfonyl)‐1,4‐epoxybenzo[d]heptalenes 25 . The latter turned out to be excellent Michael acceptors for H₂O₂ in basic media (Scheme 9). The Michael adducts lost H₂O on treatment with Ac₂O in pyridine and gave the 3‐(phenylsulfonyl)benzo[d]heptalen‐2‐ones 28a and 3‐exo‐ 28b , respectively. Rearrangement of these compounds in the presence of Ac₂O/AcONa lead to the formation of the corresponding 3‐(phenylsulfonyl)benzo[a]heptalene‐1,2‐diol diacetates 30a and 30b , which on treatment with MeONa/MeI gave the corresponding MeO‐substituted compounds 31a and 31b . The reductive elimination of the PhSO₂ group led finally to the 1,2‐dimethoxybenzo[a]heptalenes 32a and 32b . Deprotonation experiments of 32a with t‐BuLi/N,N,N′,N′‐tetramethylethane‐1,2‐diamine (tmeda) and quenching with D₂O showed that the most acid C? H bond is H? C(3) (Scheme 9). Some of the new structures were established by X‐ray crystal‐diffraction analyses (cf. Figs. 1, 3, 4, and 5). Moreover, nine of the new benzo[a]heptalenes were resolved on an anal. Chiralcel OD‐H column, and their CD spectra were measured (cf. Figs. 8 and 9). As a result, the 1,2‐dimethoxybenzo[a]heptalenes 32a and 32b showed unexpectedly new Cotton‐effect bands just below 300 nm, which were assigned to chiral exciton coupling between the heptalene and benzo part of the structurally highly twisted compounds. The PhSO₂‐substituted benzo[a]heptalenes 30b and 31b showed, in addition, a further pair of Cotton‐effect bands in the range of 275–245 nm, due to chiral exciton coupling of the benzo[a]heptalene chromophore and the phenylsulfonyl chromophore (cf. Fig. 10).     

Visible‐Light‐Promoted Generation of α‐Ketoradicals from Vinyl‐bromides and Molecular Oxygen: Synthesis of Indenones and Dihydroindeno[1,2‐c]chromenes

Ortho‐alkynylated α‐bromocinnamates can be converted by a visible‐light‐mediated photocascade reaction with molecular oxygen into either indenones or dihydroindeno[1,2‐c]chromenes. The one‐step process features key photochemical steps, that is, the initial activation of vinyl bromides through energy transfer to give α‐ketoradicals in a reaction with molecular oxygen, followed by α‐oxidation of an arene moiety by 6‐π electrocyclization, and subsequent hydroxylation by an electron‐transfer process from the same photocatalyst leads to the dihydroindeno[1,2‐c]chromenes.     

Efficient Synthesis of Pyrrolo[2,1‐a]isoquinoline and Pyrrolo[1,2‐a]quinoline Derivatives via One‐pot Two‐step Metal‐catalyzed Three‐component Reactions

A sequential one‐pot two‐step reaction for efficient synthesis of pyrrolo[2,1‐a]isoquinoline and pyrrolo[1,2‐a]quinoline derivatives in good yields has been successfully developed. The reaction included firstly Cu‐catalyzed three‐component reaction of isoquinoline (quinoline), acetylenedicarboxylate and alkynylbenzene and then Pd‐catalyzed intramolecular C(sp)‐C(sp²) coupling reaction of initially formed 1‐alkenyl‐2‐alkynyl‐1,2‐dihydroisoquinoline (1,2‐dihydroquinoline).     

Rearrangement of spiro[2H‐1‐benzopyran‐2,2′‐[2H]indoles] to pyrrolo[1,2‐a]indole derivatives

Heating of 1′‐(N‐substituted carbamoyl)methylspiro[2H‐1‐benzopyran‐2,2′‐[2H]indoles] with potassium hydroxide in ethanol yields diastereomeric 5a,13‐methano‐6H‐1,3‐benzoxazepino[3,2‐a]indole‐12‐carbox‐amides. Reduction of the latter with sodium borohydride affords 1,2,3,9a‐tetrahydro‐2‐hydroxyaryl‐9H‐pyrrolo[ 1,2‐a] indole‐3 ‐carboxamides.