Anomalous fluorescence spectra of benz[a]azulene derivatives

The electronic and fluorescence spectra of banz[a]azulene derivatives have been measured. the fluorescence from the second excited singlet state have been observed for these compounds. The fluorescence quantum yields (φ_f) is sensitive to the energy difference between the first excited singlet (S₁) and the second excited singlet state (S₂).     

Anomalous fluorescence spectrum of azuleno[1,2-b]pyrrole

Electronic and fluorescence spectra of azuleno[1,2-b]pyrrole, which is an iso-π-electron system of benz[a]azulene, have been measured. The an     

Benzo[a]azulenediones and 10,10′‐Bibenzo[a]azulene

The oxidation of benzo[a]azulene ( 4 ) with commercial MnO₂ in dioxane/H₂O leads to a number of products in low yield (Table 1). Treatment of 4 with ‘mild’ MnO₂ (MnO₂/C) in dioxane/5% H₂O results in the formation of 10,10′‐bibenzo[a]azulene ( 18 ) in yields of up to 59% of isolated and purified material. Compound 18 exhibits atropisomerism and can be separated by HPLC on a Chiralcel column at room temperature into its stable antipodes (Fig.).     

An Efficient Straightforward Synthesis of Benz[a]azulene

Benz[a]azulene ( 1 ) is synthesized in five steps (cf. Scheme 2) starting from commercially available 2-iodobenzyl alcohol ( 4 ) and tropylium tetrafluoroborate in an overall yield of 44%. The key step (cf. also Scheme 1) is the intramolecular Heck reaction of the 8-phenylsulfonyl-substituted heptafulvene 7 , which leads in nearly quantitative yield directly to 10-(phenylsulfonyl)benz[a]azulene ( 8 ). The desulfonylation of 8 can be accomplished by Julia's method with Na₂S₂O₄/NaHCO₃ in DMF/H₂O at 85–90°, thus leading to pure 1 in 78% yield. The phenylation of 8 with PhLi or PhCul at ?78° in THF occurs regioselectively at C(9). Dehydrogenation of the formed dihydroazulenes with o-chloroanil in toluene at room temperature gives 9-phenyl-10-(phenylsulfonyl)-benz[a]azulene ( 9 ) in 70% yield (cf. Scheme 3), which, again, can be desulfonylated with Na₂S₂O₄/NaHCO₃ in DMF/H₂O in good yields. The addition of PhLi to 1 in THF occurs at temperatures ? ?25°. Ionic dehydrogenation (1. Ph₃C⁺BF/MeCN; 2. Et₃N) of the dihydro forms leads to 3 , as the main product, and its positional isomers.     

An Analysis of the Bonding Properties of Benz[a]azulene by X-Ray,NMR, and Computational Studies

The X-ray crystal structures of 9-phenylbenz[a]azulene ( 4 ) and the corresponding non-benzannelated form, 4-phenylazulene ( 5 ), have been determined (cf. Fig.2). In contrast to 5 , the skeleton of which shows nearly equal C,C bond lengths (cf. Table 1), the seven-membered ring of 4 exhibits clearly alternating C,C bond lengths (cf. Table 1). This is in agreement with a strong accentuation of the heptafulvene substructure in 4 by the [a] benzannelation. The alternating bond lengths of 4 and of its parent structure 3 are also reflected in the corresponding variations of the ³J(H,H) and ¹J(¹³C,¹³C) values of these benz[a]azulenes (cf. Tables 4 and 5). Computations on the MP2/6-31G^* level as well as on the BP86/6-31G^* level for azulene ( 6 ), benz[a]azulene ( 3 ), and heptafulvene ( 7 ) are in good agreement with the experimental values (cf. Tables 6–8).     

Synthesis of Novel Disubstituted Pyrazolo[1,5‐a]pyrimidines,Imidazo[1,2‐a]pyrimidines,and Pyrimido[1,2‐a]benzimidazoles Containing Thioether and Aryl Moieties

A series of novel 6‐[(1,3,4‐thiadiazol‐2‐yl)sulfanyl]‐7‐phenylpyrazolo[1,5‐a]pyrimidines, 5‐phenyl‐6‐[(1,3,4‐thiadiazol‐2‐yl)sulfanyl]imidazo[1,2‐a]pyrimidines, and 2‐phenyl‐3‐[(1,3,4‐thiadiazol‐2‐yl)sulfanyl]pyrimido[1,2‐a]benzimidazoles have been synthesized in four steps starting with 2‐hydroxyacetophenone. The intermediate 3‐[(1,3,4‐thiadiazol‐2‐yl)sulfanyl]‐4H‐1‐benzopyran‐4‐ones reacted with pyrazol‐3‐amines, 5‐methylpyrazol‐3‐amine, and 1H‐imidazol‐2‐amine, 1H‐benzimidazol‐2‐amine via a cyclocondensation to give the title compounds in the presence of MeONa as base, respectively. The approach affords the target compounds in acceptable‐to‐good yields. The new compounds were characterized by their IR, NMR, and HR mass spectra.     

Optimized scale up of 3-pyrimidinylpyrazolo[1,5-a]pyridine via Suzuki coupling; a general method of accessing a range of 3-(hetero)arylpyrazolo[1,5-a]pyridines

We have developed an improved synthesis of 3-(hetero)aryl pyrazolo[1,5-a]pyridines (such as 3-(2,5-dichloropyrimidin-4-yl)pyrazolo[1,5-a]pyridine (8)) via an optimized synthesis and Suzuki coupling of 3-pyrazolo[1,5-a]pyridine boronic ester 10. These conditions are applicable to both high throughput chemistry and large scale synthesis of these medicinally important compounds. The scope of this chemistry has been further extended to include the synthesis and coupling of a novel boronic ester, 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine (43).     

Magnetic circular dichroism of azuleno[1,2-b]azulene derivatives

Both 6,12-diphenylazuleno[1,2-b] azulene and 6,12-di-p-bromophenylazuleno [1,2-b] azulene exhibit similar absorption and MCD spectra. PPP calculations reproduce the observed absorption and MCD spectra. The phenyl and p-bromophenyl groups are considered to present no obstacle in investigating the spectroscopic behavior of azuleno[1,2-b] azulene.     

Synthesis and some properties of N-unsubstituted pyrrolo[2,1-c]-1,3-diazacycloalkano[1,2-a]pyrazinones

Reactions of methyl 2-(2-formyl-1H-pyrrol-1-yl)alkanoates with unsubstituted aliphatic 1,2-, 1,3-, and 1,4-diamines gave N-unsubstituted pyrrolo[2,1-c]-1,3-diazacycloalkano[1,2-a]-pyrazinones. Some of them show ring-chain tautomerism. Transformations of these compounds led to a number of novel heterocyclic systems: 2,10-dihydro-3H,5H-imidazo[1,2-a]-pyrrolo[1,2-d]pyrazines, 2,3,4,11-tetrahydro-6H-pyrrolo[1??,2??:4,5]pyrazino[1,2-a]pyrimidines, 1,2,3,5,6,10b-hexahydroimidazo[1,2-a]pyrrolo[2,1-c]pyrazines, 1,3,4,6,7,11b-hexahydro-2H-pyrrolo[2??,1??:3,4]pyrazino[1,2-a]pyrimidines, and 2,3,4,5,6,7-hexahydro-1H-pyrrolo[2,1-c]-[1,4,7]triazacycloundecin-8(9H)-one.     

Asymmetric construction of pyrido[1,2-a]-1H-indole derivatives via a gold-catalyzed cycloisomerization

Pyrido[1,2-a]-1H-indoles are important scaffolds found in many biologically active compounds. Herein, we first developed an IPrAuCl/AgSbF₆-catalyzed cycloisomerization of N-1,3-disubstituted allenyl indoles affording pyrido[1,2-a]-1H-indoles. Then the axial-to-central chirality transfer starting from enantio-enriched N-1,3-disubstituted allenylindoles affording optically active pyrido[1,2-a]-1H-indoles has been realized in excellent yields and enantioselectivities. A mechanism has been proposed based on mechanistic studies. Synthetic applications have also been demonstrated.

We reported an IPrAuCl/AgSbF₆-catalyzed cycloisomerization of enantio-enriched N-1,3-disubstituted allenylindoles affording optically active pyrido[1,2-a]-1H-indoles in excellent yields and enantioselectivities.     

A Detailed Investigation of the Reaction of 5,9-Diphenylbenz[a]azulene with Dialkyl Acetylenedicarboxylates Leading to Dialkyl 8,12-Diphenylbenzo[a]heptalene-6,7-dicarboxylates

The synthesis of 5,9-diphenylbenz[a]azulene ( 1 ) from 1,3-diphenylcyclopent[a]indene-2,8-dione ( 4 ) and cyclopropene has been re-investigated. The reduction of the decarbonylated cycloadduct 5 with LiAlH₄/AlCl₃ in Et₂O leads not only to the expected 7,10-dihydrobenz[a]azulene 6 , but also to small amounts of the cyclopropa[b]fluorenes exo- 7 and endo- 7 (cf. Scheme 2), the structures of which have been determined by X-ray crystal-structure analysis (cf. Fig. 1). The reaction of 1 with dialkyl acetylenedicarboxylates (ADR) in MeCN at 100° in the presence of 2 mol-% of catalysts such as [RuH₂(PPh₃)₄] results mainly in the formation of the expected 8,12-diphenylbenzo[a]heptalene-6,7-dicarboxylates 3 . A thorough investigation of the reaction mixture of 1 and dimethyl acetylenedicarboxylate (ADM) revealed the presence of a number of intermediates and side products (Scheme 5). Most important was the isolation and identification of the cyclobutene intermediate 9a (cf. Fig. 4), which is formed by a zwitterionic rearrangement of the primary adduct 2a of 1 and ADM and represents the direct precursor of the heptalene-diester 3a . Compounds of type 9a have so far only been postulated as necessary intermediates in the thermal reaction of azulenes and ADR to give corresponding heptalenedicarboxylates. Compound 9a is photochemically unstable and undergoes rearrangement even under the influence of normal laboratory light into a mixture of trans- 10a and cis- 10a (Scheme 8). Both diastereoisomers are also found in the original reaction mixture of 1 and ADM, but not when the reaction is performed under exclusion of light. On heating in MeCN at 100°, or better in DMF at 150°, trans- 10a and cis- 10a undergo rearrangement to the fluoranthene-1,2-dicarboxylate 11a (Scheme 9), which is also present in the original reaction mixture of 1 and ADM. The catalysts do not accelerate the reaction of 1 and ADR, but they lead to better yields of the benzo[a]heptalene-6,7-dicarboxylates 3 , especially in the reaction of 1 with diisopropyl acetylenedicarboxylate (ADiP) (cf. Tables 1 and 2).     

Azulene–Naphthalene‐Type Rearrangements in Benz[a]azulene and Cyclohepta[b]indole

Flash vacuum pyrolysis (FVP) of benz[a]azulene yields phenanthrene and 2‐ethynylbiphenyl. FVP of cyclohepta[b]indole similarly yields phenanthridine and 2‐cyanobiphenyl. The reversibility of the reactions is demonstrated by FVP of 2‐ethynylbiphenyl and 2‐isocyanobiphenyl. All the observed reactions are in accord with the norcaradiene–vinylidene mechanism of the azulene–naphthalene rearrangement, whereas other proposed mechanisms are ruled out.     

The synthesis of 11H-1,2,4-triazolo[4,3-b]pyridazino[4,5-b]indoles,11H-tetrazolo[4,5-b]pyridazino[4,5-b]indoles and 1,2,4-triazolo[3,4-f]-1,2,4-triazino[4,5-a]indoles

This paper describes the synthesis of the previously unknown 11H-1,2,4-triazolo[4,3-b]pyridazino[4,5-b]indoles (2) and 11H-tetrazolo[4,5-b]pyridazino[4,5-b]indoles (3) from 4-hydrazino-5H-pyridazino[4,5-b]indoles (1) , as well as the synthesis of 1,2,4-triazolo[3,4-f]-1,2,4-triazino-[4,5-a]indoles (10) from 2-indolecarbohydrazide (4) . Compounds 2 were obtained by acylation of compounds 1 , followed of thermal cyclization and compounds 3 by treating compounds 1 with nitrous acid. The reactions of compound 4 with formic acid or ethyl orthoformiate gave 1,2-dihydro-1-oxo-1,2,4-triazino[4,5-a]indole (6) . Treating this last compound with phosphorus oxychloride or phosphorus pentasulfide, followed by hydrazine, gave 1-hydrazino-1,2,4-triazino-[4,5-a]indole (9) . Acylation of this last compound, followed of cyclization gave compounds 10 . All the compounds were characterized by elemental analysis and ir and ¹H-nmr spectra.     

Synthesen von basisch substituierten ([1]Benzo-)Thieno-[2,3—d]pyrimidin-Derivaten und von ([1]Benzo-)Thieno-[2,3-d]-1,2,4-triazolo[4,3-a]pyrimidin-Derivaten

Reaction of 2-methylthio-thieno[2.3-d]pyrimidin-4(3H)-ones with heterocyclic secondary amines, ethanolamine and hydrazine, resp., gave the corresponding derivatives with a basic substituent in position 2. Cyclization of the hydrazino compounds with formic acid gave derivatives of thieno[2.3-d]-1.2.4-triazolo[4.3-a]pyrimidine and [1]benzothieno[2.3-d]-1.2.4-triazolo[4.3-a]pyrimidine, two new heterocyclic systems.     

Synthesis and spectroscopic characterizations of both 4b,5-dihydro-4b-methyl-11H-isoindolo[2,1-a]benzimidazol-11-ones and 2,3,3a,4-tetrahydro-3a-methyl-1H-pyrrolo[1,2-a]benzimidazol-1-ones

The complete assignment of the ¹H and ¹³C nmr spectra of some derivatives of both 4b,5-dihydro-4b-methyl-11H-isoindolo[2,1-a]benzimidazol-11-one I and 2,3,3a,4-tetrahydro-3a-methyl-1H-pyrrolo[1,2-a]-benzimidazol-1-one II was herein reported by the combined use of one and two-dimensional nmr techniques. Eight compounds, three of which are novel, 2a, 3, 6 , were thus prepared. Their uv and ir spectra were also obtained. In addition, the mass spectra of compounds 1, 2a, 2b, 3 and 6 are reported.     

Synthesis,Antibacterial and Antifungal Activity of New 3-Aryl-5H-pyrrolo[1,2-a]imidazole and 5H-Imidazo[1,2-a]azepine Quaternary Salts

A series of novel 3-aryl-5H-pyrrolo[1,2-a]imidazole and 5H-imidazo[1,2-a]azepine quaternary salts were synthesized in 58–85% yields via the reaction of 3-aryl-6, 7-dihydro-5H-pyrrolo[1,2-a]imidazoles or 3-aryl-6,7,8,9-tetrahydro-5H-imidazo[1,2-a]azepines and various alkylating reagents. All compounds were characterized by ¹H NMR, ¹³C NMR, and LC-MS. The conducted screening studies of the in vitro antimicrobial activity of the new quaternary salts derivatives established that 15 of the 18 newly synthesized compounds show antibacterial and antifungal activity. Synthesized 3-(3,4-dichlorohenyl)-1-[(4-phenoxyphenylcarbamoyl)-methyl]-6,7-dihydro-5H-pyrrolo[1,2-a]imidazol-1-ium chloride 6c possessed a broad activity spectrum towards Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, and Cryptococcus neoformans, with a high hemolytic activity against human red blood cells and cytotoxicity against HEK-293. However, compound 6c is characterized by a low in vivo toxicity in mice (LD₅₀ > 2000 mg/kg).     

Microwave assisted synthesis of 2,3-dihydro-4H-benzo[4,5]thiazolo[3,2-a]furo[2,3-d]pyrimidin-4-ones and 6,7-dihydro-5H-furo[2,3-d]thiazolo[3,2-a]pyrimidin-5-ones using Mn(OAc)3

2-Hydroxy-4H-benzo[4,5]thiazolo[3,2-a]pyrimidin-4-one 2a and 7-hydroxy-5H-thiazolo[3,2-a]pyrimidin-5-one 2b, were obtained in high yields under mild conditions from the cyclization reactions of bis-(2,4,6-trichlorophenyl) malonate and 2-aminobenzothiazole or 2-aminothiazole, respectively. A new class of compounds, 2,3-dihydro-4H-benzo[4,5]thiazolo[3,2-a]furo[2,3-d]pyrimidin-4-ones and 6,7-dihydro-5H-furo[2,3-d]thiazolo[3,2-a]pyrimidin-5-ones, were synthesized via the microwave assisted radical addition of compounds 2a and 2b to various alkenes using manganese(III) acetate. A preliminary acetylcholine esterase (AchE) inhibition test of compound 4e showed excellent (92%) inhibitory potential, comparable with the standard drug Donapezil®.     

Imidazo- und Diazino-Anellierungen an das [1]Benzothieno[2,3—d]pyrimidin-System

Derivatives of the following six ring systems were synthesized:

1. 3,10-Dihydro-[1]benzothieno[2,3-d]imidazo[1,5-a]-pyrimidine (I)
2. 6H-[1]Benzothieno[2,3-d]pyrazino[1,2-a]pyrimidine (II)
3. 1,5-Dihydro-[1]benzothieno[2,3-d]imidazo[1,2-a]-pyrimidine (III)
4. 6H-[1]Benzothieno[2,3-d]pyrimido[1,2-a]pyrimidine (IV)
5. 1,5-Dihydro-imidazo[1,2-a]thieno[2,3-d]pyrimidine (V)
6. 4H-Pyrimido[1,2-a]thieno[2,3-d]pyrimidine (VI)

The first four types are new heterocyclic systems. 2-Aminomethyl-5,6,7,8-tetrahydro-[1]benzothieno[2,3-d]pyrimidin-4(3H)-one (5), which was used as intermediate for typesI andII, was synthesized by various methods. TypesIII andIV were prepared from 2-methylthio-5,6,7,8-tetrahydro-[1]-benzothieno[2,3-d]pyrimidin-4(3H)-one via the corresponding 2-benzylamino derivatives, followed by ring closure.     

Synthese von Thiazolo[3,2−a]thieno[2,3−d]pyrimidin-Derivaten

Derivatives of 5H-thiazolo[3.2?a]thieno[2.3?d]pyrimidine(A), 5H-[1]benzothieno[2.3?d]thiazolo[3.2?a]pyrimidine (B), 4H-thiazolo[3.2?a]thieno[3.2?e]pyrimidine (C) and 5H-[1]benzo-thieno[3.2?e]thiazolo[3.2?a]pyrimidine (D) were synthesized by various methods. Similar reactions are leading to derivatives of thieno[2′.3′∶4.5]pyrimido[2.1?b][1.3]thiazine (E) and [1]benzothieno[2′.3′∶4.5]pyrimido[2.1?b][1.3]thiazine (F).C, D, E, andF are new heterocyclic ring systems. Detailed papers will appear soon.     

Synthesis and properties of 3-arylcyclohepta[4,5]imidazo[1,2-a]-1,3,5-triazine-2,4(3H)-diones and related compounds: photo-induced autorecycling oxidation of some amines

Novel 3-phenyl- and 3-(4-nitrophenyl)cyclohepta[4,5]imidazo[1,2-a]-1,3,5-triazine-2,4(3H)-diones and the corresponding imino derivatives 5a,b and 6a,b were synthesized in modest to moderate yields by the abnormal and normal aza-Wittig reaction of 2-(1,3-diazaazulen-2-ylimino)triphenylphosphorane with aryl isocyanates and subsequent heterocyclization reaction with a second isocyanate. The related cationic compound, 1-methyl-3-phenylcyclohepta[4,5]imidazo[1,2-a]-1,3,5-triazine-2,4(3H)-dionylium tetrafluoroborate 7a, was also prepared. The electrochemical reduction of these compounds exhibited more positive reduction potentials as compared with those of the related compounds of 3,10-disubstituted cyclohepta[4,5]pyrrolo[2,3-d]pyrimidine-2,4(1H,3H)-dione systems. In a search of the oxidizing ability, compounds 5a, 6a, and 7a were demonstrated to oxidize some amines to give the corresponding imines in more than 100% yield under aerobic and photo-irradiation conditions, while even benzylamine was not oxidized under aerobic and thermal conditions at 100 °C. The oxidation reactions by cation 7a are more efficient than that by 5a and 6a. Quenching of the fluorescence of 5a was observed, and thus, the oxidation reaction by 5a probably proceeds via electron-transfer from amine to the excited singlet state of 5a. In the case of cation 7a, the oxidation reaction is proposed to proceed via formation of an amine-adduct of 7a and subsequent photo-induced radical cleavage reaction.