Ring transformation of cyclohepta[b]pyrimido[5,4-d]furan-8(7H),10(9H)-dionylium ion to the corresponding pyrrole derivatives via troponeimine intermediates: photo-induced autorecycling oxidizing reactions of some amines

Ring transformation of 7,9-dimethylcyclohepta[b]pyrimido[5,4-d]furan- 8(7H),10(9H)-dionylium tetrafluoroborate 4⁺·BF₄⁻ to 7,9-dimethylcyclohepta[b]pyrimido[5,4-d]pyrrrole-8(7H),10(9H)-dionylium tetrafluoroborate 6a-d⁺·BF₄⁻ consists of the reaction of 4⁺·BF₄⁻ with amines and subsequent exchange of the counter-ion using aq. HBF₄. Reactions of 4⁺·BF₄⁻ with aniline and 4-substituted anilines afforded the corresponding pyrrole derivatives 6a-c⁺·BF₄⁻ directly in good yields. On the other hand, reaction of 4⁺·BF₄⁻ with benzylamine gave the troponeimine intermediate 9, which was not converted to 6d⁺·BF₄⁻ and reverted to 4⁺·BF₄⁻ by adding HBF₄; however, it was converted to 6d⁺·BF₄⁻ upon treatment with (COCl)₂ or SOCl₂, followed by exchange of the counter-ion. In a search for the characteristics of 9, inspection and comparison of the X-ray crystal analyses, NMR and UV-vis spectra, and CV measurement of 9 and N,N-disubstituted troponeimine derivatives 12 were carried out to suggest the remarkable structure of 12 having ionic C-O bonding between the imine-carbon atom and the oxygen atom of the barbituric acid moiety in the solid state. Thus, characteristics of 9 were ascribed to the sterically hindered and favorable conformation of N-protonated troponeimine intermediates. Furthermore, novel photo-induced oxidation reactions of a series of 4⁺·BF₄⁻, 5⁺·BF₄⁻, and 6a,e⁺·BF₄⁻ towards some amines under aerobic conditions were carried out to give the corresponding imines in 455-8362% yields [based on compounds 4⁺, 5⁺, and 6a,e⁺], suggesting the oxidation reaction occurs in an autorecycling process. Mechanistic aspects of the amine-oxidation reaction are also postulated.     

Synthesis and properties of novel 5-(cyclohepta-2′,4′,6′-trienylidene)pyrimidine-2(1H),4(3H),6(5H)-triones: methodology for synthesizing cyclohepta[b]pyrimido[5,4-d]furan-8(7H),10(9H)-dionylium tetrafluoroborates

Novel condensation reaction of tropone with N-substituted and N,N′-disubstitued barbituric acids in Ac₂O afforded 5-(cyclohepta-2′,4′,6′-trienylidene)pyrimidine-2(1H),4(3H),6(5H)-trione derivatives (8a-f) in moderate to good yields. The ¹³C NMR spectral study of 8a-f revealed that the contribution of zwitterionic resonance structures is less important as compared with that of 8,8-dicyanoheptafulvene. The rotational barriers (ΔG^‡) around the exocyclic double bond of mono-substituted derivatives 8a-c were obtained to be 14.51-15.03 kcal mol⁻¹ by the variable temperature ¹H NMR measurements. The electrochemical properties of 8a-f were also studied by CV measurement. Upon treatment with DDQ, 8a-c underwent oxidative cyclization to give two products, 7 and 9-substituted cyclohepta[b]pyrimido[5,4-d]furan-8(7H),10(9H)-dionylium tetrafluoroborates (11a-c·BF₄⁻ and 12a-c·BF₄⁻) in various ratios, while that of disubstituted derivatives 8d-f afforded 7,9-disubstituted cyclohepta[b]pyrimido[5,4-d]furan-8(7H),10(9H)-dionylium tetrafluoroborate (11d-f·BF₄⁻) in good yields. Similarly, preparation of known 5-(1′-oxocycloheptatrien-2′-yl)-pyrimidine-2(1H),4(3H),6(5H)-trione derivatives (14a-d) and novel derivatives 14e,f was carried out. Treatment of 14a-c with aq. HBF₄/Ac₂O afforded two kinds of novel products 11a-c·BF₄⁻ and 12a,c·BF₄⁻ in various ratios, respectively, while that of 14d-f afforded 11d-f. The product ratios of 11a-c·BF₄⁻ and 12a-c·BF₄⁻ observed in two kinds of cyclization reactions were rationalized on the basis of MO calculations of model compounds 20a and 21a. The spectroscopic and electrochemical properties of 11a-f·BF₄⁻ and 12a-c·BF₄⁻ were studied, and structural characterization of 11c·BF₄⁻ based on the X-ray crystal analysis and MO calculation was also performed.     

Novel synthesis and properties of 7,9-dimethylcyclohepta[b]pyrimido[5,4-d]furan-8(7H),10(9H)-dionylium tetrafluoroborate: autorecycling oxidation of some alcohols under photo-irradiation

Three-step reactions starting from 2-chlorotropone with barbituric acid afforded novel 7,9-dimethylcyclohepta[b]pyrimido[5,4-d]furan-8(7H),10(9H)-dionylium tetrafluoroborate (9·BF₄⁻), which is the isoelectronic compound of the 5-ethyl-3-methyllumiflavinium ion. The stability of cation 9 is expressed by the pK_R+ value, which was determined spectrophotometrically, as ca. 6.0. The electrochemical reduction of 9 exhibited low reduction potential at −0.58 (V vs Ag/AgNO₃), upon cyclic voltammetry (CV). In a search for the reactivity, reactions of 9·BF₄⁻ with some nucleophiles, hydroxide, hydride, amines, thiols, and methanol, were carried out to exhibit that the introduction of nucleophiles is dependent on the nucleophile itself. The photo-induced oxidation reactions of some alcohols catalyzed by 9·BF₄⁻ under aerobic conditions were carried out to give the corresponding carbonyl compounds in more than 100% yield [based on compound 9·BF₄⁻], suggesting the oxidizing function of 9·BF₄⁻ toward alcohols in the autorecycling process. The UV-vis and fluorescence spectra of 9 were studied to suggest the electron transfer from alcohols to the excited 9.     

Novel photo-induced oxidative cyclization of 1,3-dimethyl-5-(1-arylmethylidene)pyrimidine-2,4,6(1,3,5H)-triones: synthesis and properties of areno[5,6]pyrano[2,3-d]pyrimidine-2,4(1,3H)-dionylium ions and their photo-induced autorecycling oxidizing reaction toward some amines

Novel photo-induced oxidative cyclization was accomplished to synthesize areno[b]pyrimido[5,4-e]pyran-2,4(1,3H)-dionylium ions 13a-c⁺·ClO₄⁻. Furthermore, 13a-c⁺·BF₄⁻ and their phenyl-substituted derivatives 19a,b⁺·BF₄⁻ were alternatively synthesized by the reaction of salicylaldehyde and its naphthyl derivatives with barbituric acids and subsequent treatment with aq. HBF₄. Structural characteristics of 13a-c⁺ and 19a,b⁺ were clarified on inspection of the UV-vis and NMR spectral data as well as X-ray crystal analyses. The electrochemical properties were studied by the CV measurement. In a search for reactivity, reactions of 13a-c⁺·BF₄⁻ with some nucleophiles, hydride, benzylamine, and H₂O, were also carried out. The photo-induced autorecycling oxidation reactions of 13a-c⁺·BF₄⁻ toward some amines under aerobic conditions were carried out to give the corresponding imines (isolated by converting to the corresponding 2,4-dinitrophenylhydrazones) in 643-3600% yield (recycling number of 13a-c⁺·BF₄⁻: 6.4-36.0).     

Novel synthesis and properties of 7,9-dimethylcyclohepta[b]pyrimido[5,4-d]thiophen-8(7H),10(9H)-dionylium tetrafluoroborate: autorecycling oxidation of some alcohols under photo-irradiation

Three-step reactions starting from 2-chlorotropone with dimethylthiobarbituric acid afforded 7,9-dimethylcyclohepta[b]pyrimido[5,4-d]thiophen-8(7H),10(9H)-dionylium tetrafluoroborate 5·BF₄⁻, which is the isoelectronic compound of the 5-ethyl-3-methyllumiflavinium ion. The X-ray crystal analysis and MO calculation were carried out to clarify the structural characteristics of 5·BF₄⁻. The stability of cation 5 is expressed by the pK_R+ value, which was determined spectrophotometrically as 5.1. The electrochemical reduction of 5 exhibited low reduction potential at −0.53 (V vs Ag/AgNO₃), upon cyclic voltammetry (CV). In a search for the reactivity, reactions of 5·BF₄⁻ with some nucleophiles, hydride, diethylamine, thiols, and methanol, were carried out, which revealed that the introduction of nucleophiles to give regio-isomers is dependent on the nucleophile. The photo-induced oxidation reactions of 5·BF₄⁻ toward some alcohols under aerobic conditions were carried out to give the corresponding carbonyl compounds in more than 100% yield [based on compound 5·BF₄⁻], suggesting the oxidizing function of 5·BF₄⁻ toward alcohols in the autorecycling process. The UV-vis and fluorescence spectra of 5 were studied to suggest the electron transfer from alcohols to the excited 5.     

Alternative synthesis and novel oxidizing ability of 6,9-disubstituted cyclohepta[b]pyrimido[5,4-d]pyrrole-8(6H),10(9H)-dione derivatives

Synthesis of 6,9-disubstituted cyclohepta[b]pyrimido[5,4-d]pyrrole-8(6H),10(9H)-diones 7a-g was accomplished by ring opening and ring closure sequences of 9-substituted cyclohepta[b]pyrimido[5,4-d]furan-8,10(9H)-dione derivatives induced by several amines. Furthermore, alternative synthetic methodology for compounds 7a-e was also accomplished by single-step reaction of 2-chlorotropone with 6-aminouracil derivatives under mild conditions. X-ray crystal analysis of 7a was carried out to clarify the structural characteristics. The properties of 7a-e were studied by the UV-vis spectra and reduction potentials (−1.24 to −1.39 V vs Ag/AgNO₃). Novel photo-induced oxidation reaction of 7a-d toward some amines under aerobic conditions was carried out to give the corresponding imines in more than 100% yield [based on compounds 7a-d], suggesting the oxidation reaction occurs in an autorecycling process.     

Synthesis and properties of 4,9-methanoundecafulvenes and their transformation to 3-substituted 7,12-methanocycloundeca[4,5]furo[2,3-d]pyrimidine-2,4(1H,3H)-diones: photo-induced autorecycling oxidizing reaction toward amines

The synthesis and properties of 4,9-methanoundecafulvene [5-(4,9-methanocycloundeca-2′,4′,6′,8′,10′-pentaenylidene)pyrimidine-2,4,6(1,3,5H)-trione] derivatives 8a,b were studied. Their structural characteristics were investigated on the basis of the ¹H and ¹³C NMR and UV-vis spectra. The rotational barrier (ΔG^‡) around the exocyclic double bond of 8a was found to be 12.55 kcal mol⁻¹ by the variable temperature ¹H NMR measurement. The electrochemical properties of 8a,b were also studied by CV measurement. Furthermore, the transformation of 8a,b to 3-substituted 7,12-methanocycloundeca[4,5]furo[2,3-d]pyrimidine-2,4(1H,3H)-diones 16a,b was accomplished by oxidative cyclization using DDQ and subsequent ring-opening and ring-closure. The structural details and chemical properties of 16a,b were clarified. Reaction of 16a with deuteride afforded C13-adduct 19 as the single product, and thus, the methano-bridge controls the nucleophilic attack to prefer endo-selectivity. The photo-induced oxidation reaction of 16a and a vinylogous compound, 3-methylcyclohepta[4,5]furo[2,3-d]pyrimidine-2,4(3H)-dione 2a, toward some amines under aerobic conditions were carried out to give the corresponding imines (isolated by converting to the corresponding 2,4-dinitrophenylhydrazones) with the recycling number of 6.1-64.0 (for 16a) and 2.7-17.2 (for 2a), respectively.     

Synthesis and pharmacological evaluation of 6a,7-dihydro-6H,13H-pyrazino[1,2-a;4,5-a′]diindole analogs as melatonin receptor ligands

The synthesis of two melatonin-derived analogs of the novel 6a,7-dihydro-6H,13H-pyrazino[1,2-a;4,5-a′]diindole ring system is described. The non-methoxy and methoxy analogs, 4a and 4b were prepared in seven steps starting from indoline-2-carboxylic acid 5a and 5-methoxyindoline-2-carboxylic acid 5b, respectively. While 4a exhibited micromolar affinities for both melatonin receptors, the methoxy analog 4b displayed moderate affinity for MT₂ receptors (K_i=0.41 μM) being 4.4-fold higher than for the MT₁ subtype.     

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.     

Quinoxalines. Part 12: Synthesis and structural study of 1-(thiazol-2-yl)-1H-pyrazolo[3,4-b]quinoxalines—the dehydrogenative cyclization with hydroxylamine hydrochloride

Starting with 2-acetylquinoxaline a novel class of heterocyclic compounds, the 1-(thiazol-2-yl)-1H-pyrazolo[3,4-b]quinoxalines 4, were prepared by following two different synthetic procedures: 2-acetylquinoxaline reacted with thiosemicarbazide to the thiosemicarbazones 1a which was (i) cyclized with α-halogeno ketones to the thiazoles 3. These compounds were dehydrogenated in acidic medium to the title compounds 4. (ii) The thiosemicarbazone 1a could be also dehydrogenated using NH₂OH·HCl to the thioamide 5a and these, finally, were cyclized with α-halogeno ketones to the title compounds 4. Only thiazole 3a was isolated, the other thiazoles 3 were dehydrogenated in a one-pot procedure. From the thioamide 5a also both the compounds 9, by reacting with dibromodiacetyl, and 10, by treatment with dimethyl acetylenedicarboxylate, were obtained. The analysis of both the ¹H and ¹³C NMR spectra was not straightforward but could be attained finally by employing the whole arsenal of 1D and 2D NMR spectroscopy.     

Application and details of photoinduced oxidative cyclization of 5-(4′,9′-methanocycloundeca-2′,4′,6′,8′,10′-pentaenylidene)pyrimidine-2,4,6(1,3,5H)-triones and related compounds

As novel methodology for synthesizing the furan ring, a photoinduced oxidative cyclization of 5-(4′,9′-methanocycloundeca-2′,4′,6′,8′,10′-pentaenylidene)pyrimidine-2,4,6(1,3,5H)-triones (7a-c) and related compounds 9a-c was accomplished to give 5,10-methanocycloundeca[4,5]furo[2,3-d]pyrimidine-2,4(1,3H)-dionylium tetrafluoroborates (8a-c⁺·BF₄⁻) and related compounds 2a-c⁺·BF₄⁻, respectively. In the photoinduced oxidative cyclization, the molecular oxygen in air is used as oxidant and the reaction proceeds under mild conditions to give desired products without byproducts, and thus, it is interesting from the viewpoint of the green chemistry. On the reactions of the mono-substituted derivatives 7d,e and 9e,f, the selectivity of the photoinduced cyclizations were reversed as compared with those of the DDQ-promoted oxidative cyclizations. By the NMR monitoring of the reactions of 7a and deuterated compound 7a-D₂ under degassed conditions, the details of the reaction pathway were clarified and rationalized on the basis of the MO calculation by the 6-31G^∗ basis set of the MP2 levels as well.     

Preparation of new pyrido[3,4-b]thienopyrroles and pyrido[4,3-e]thienopyridazines

Two new types of pyrido-fused tris-heterocycles (1a,b and 2a,b) have been prepared from 3-aminopyridine in five/six steps. A synthetic strategy for the preparation of the novel pyrido[3,4-b]thieno[2,3- and 3,2-d]pyrroles (1a,b) and pyrido[4,3-e]thieno[2,3- and 3,2-c]pyridazines (2a,b) has been studied. The Suzuki cross coupling of the appropriate 2- and 3-thienoboronic acids (3,4) and 4-bromo-3-pyridylpivaloylamide (9) afforded the biaryl coupling products (10,11) in high yields (85%). Diazotization of the hydrolysed (2-thienyl)-coupling product (12) and azide substitution gave the 3-azido-4-(2-thienyl)pyridine intermediate (72%, 14). 3-Azido-4-(3-thienyl)pyridine (15) was prepared by exchanging the previous order of reactions. The desired β-carboline thiophene analogues (1a,b) were obtained via the nitrene by thermal decomposition of the azido precursors (14,15). By optimising conditions for intramolecular diazocoupling, the corresponding pyridazine products (72-83%, 2a,b) were afforded.     

Stabilization of (N-methyleneamino)imidoylketenes: synthesis of dipyrazolo[1,2-a;1′,2′-d][1,2,4,5]tetrazines

Thermolysis of substituted methyl 1-methyleneamino-4,5-dioxo-4,5-dihydro-1H-pyrrole-2-carboxylates 2a,b led to substituted dimethyl 3,9-dioxo-1,5,7,11-tetrahydro-1H,7H-dipyrazolo[1,2-a;1′,2′-d][1,2,4,5]tetrazine-1,7-dicarboxylates 4a,b and methyl 2,5-dihydro-5-oxo-1H-pyrazole-3-carboxylates 5a,b as minor products. The structure of compound 4a was determined by X-ray crystallography. The proposed mechanism of this conversion includes generation of (N-methyleneamino)imidoylketenes 6a,b and its intramolecular transformation to azomethine imines—5-oxo-2,5-dihydropyrazole-1-methylium-2-ides 7a,b, which undergo dimerization in head-to-tail manner yielding products 4a,b and partially hydrolyse to compounds 5a,b.     

Synthesis and properties of bis(heteroazulen-3-yl)methyl cations and bis(heteroazulen-3-yl)ketones

The synthesis and properties of a novel type of bis(heteroazulen-3-yl)methyl cations, bis(2-oxo-2H-cyclohepta[b]furan-3-yl)methyl cation salt and nitrogen analogues, (9a-c·PF₆⁻) and (9a-c·BF₄⁻), as well as bis(heteroazulen-3-yl)ketones (12a-d) are studied. The synthetic method was based on a TFA-catalyzed electrophilic aromatic substitution on the heteroazulenes (6a-d) with paraformaldehyde to afford the corresponding disubstituted methane derivatives 7a-d, followed by oxidative hydrogen abstraction with DDQ, and subsequent exchange of the counter-anion by using aq. HPF₆ or aq. HBF₄. In addition, the reaction of 7a-d with 2.2 equiv. amounts of DDQ afforded carbonyl compounds 12a-d. The delocalization of the positive charge of 9a-c was evaluated by the ¹H and ¹³C NMR spectral data. The thermodynamic stability of cations 9a-c was evaluated to be in the order 9a<9b<9c on the basis of their reduction potentials measured by cyclic voltammetry (CV) and pK_R+ values (2.6-10.3) obtained spectrophotometrically. The reduction waves of cations 9a-c were irreversible, suggesting the dimerization of the radical species generated by one-electron reduction. This was demonstrated by the reduction of 9a·BF₄⁻ with Zn powder to give dimerized product 14a. In addition, the quenching of 9a·BF₄⁻ with MeOH/NaHCO₃ gives ether derivative 15a, which is proposed for the precursor for synthesizing tris(heteroazulene)-substituted methyl cations bearing two different heteroazulene-units.     

Synthesis and photochromic behaviour of new methyl induced linear and angular thieno-2H-chromenes

New methyl induced linear and angular thieno-2H-chromenes 4, 5 and 6 were prepared by reaction of new methylated 6-hydroxybenzo[b]thiophenes 2 (a, b and c) and propargylic alcohols 3a and 3b, using acidic Alumina Brockmann I as catalyst and drying agent. Compounds 2 were prepared in good to excellent yields in a ‘one pot’ three step reaction from the corresponding bromo compounds 1. The photochromic behaviour of compounds 4, 5 and 6b was evaluated with the aid of a classical set of spectrokinetic parameters, and compared to reference compounds that are benzoannellated in the 5,6 and 6,7 positions of the chromene (naphthopyrans) and also to thieno-2H-chromenes 7 and 8, previously prepared, which are analogues of 5a. The resistance to fatigue (photodegradation) under continuous irradiation was also evaluated.     

One pot synthesis of imidazo[2,1-b]thiazoles and benzo[d]thiazolo[3,2-a]imidazoles

A series of imidazo[2,1-b]thiazole and benzo[d]thiazolo[3,2-a]imidazole analogues were synthesized by stirring an equimolar mixture of dibenzoylacetylene with imidazole/thiazole derivatives in toluene or acetonitrile at room temperature. The products were generated in good yields and characterized by standard analytical techniques such as IR, ¹H NMR, ¹³C NMR and mass spectrometry. The structure of products 19, 20, 22, 24 and 25 were also unambiguously confirmed by single crystal X-ray analysis.     

A facile approach for the synthesis of novel substituted 4H-chromenes and condensation reactions of 4H-chromenes leading to chromenopyrrolones and triazolylchromenopyrrolones

A facile method has been developed for the synthesis of 4H-chromene-3-carboxylates 3a–d by the nucleophilic substitution reaction of 2-hydroxy-2H-chromene-3-carboxylates 2a–d with triethylsilane in the presence of BF₃·O(C₂H₅)₂. Cyclocondensation of 4H-chromene-3-carboxylates 3a–d with benzylamines 4a–d afforded a series of 2,3-dihydrochromenopyrrolones 5a–p and with propargylamine afforded 2-propynyl-2,3-dihydrochromenopyrrolones 6a–d. Click reaction of 6a–d with benzyl azides 7a–d provided a series of 1H-1,2,3-triazolylmethyl-2,3-dihydrochromenopyrrolones 8a–p. Thus synthesized compounds 3a–d, 5a–p, 6a–d, and 8a–p are novel heterocyclic compounds and being reported for the first time.     

X-ray structure and multinuclear NMR studies of platinum(II) complexes with 5-methyl-1,2,4-triazolo[1,5-a]pyrimidin-7(4H)-one

New dichloride platinum(II) complexes with 5-methyl-1,2,4-triazolo[1,5-a]pyrimidin-7(4H)-one (HmtpO) have been synthesized and characterized by thermal analysis, infrared and ¹H, ¹³C, ¹⁵N, ¹⁹⁵Pt NMR spectroscopy. X-ray crystal structures of cis-PtCl₂(NH₃)(HmtpO) (1) and cis-PtCl₂(HmtpO)₂ · 4H₂O (2b) were determined to R = 0.0332 and R = 0.0802, respectively. In both complexes the Pt(II) ions have a square-planar geometry with two adjacent corners being occupied by two nitrogens of HmtpO molecules for 2b or NH₃ and HmtpO molecules for 1, whereas the remaining adjacent corners are occupied by two chloride anions. Spectroscopic data confirm the square planar geometry with N(3) bonded HmtpO, S-bonded dimethylsulfoxide and two trans chloride anions for trans-PtCl₂(dmso) · 4H₂O (3).     

A novel transformation of 1-exo-substituted 2a-aroyl-1,2,2a,8b-tetrahydro-3H-benzo[b]cyclobuta[d]pyran-3-ones with sulfoxonium ylide to highly strained 2a-(1-arylethenyl)-1,2,2a,7b-tetrahydrocyclobuta[b]benzofurans

When 1-substituted 2a-aroyl-1,2,2a,8b-tetrahydro-3H-benzo[b]cyclobuta[d]pyran-3-ones (1) were treated with dimethylsulfoxonium methylide, 1-endo isomers (endo-1) gave 1-substituted 3-aroyl-1,2,4a,9b-tetrahydrodibenzofuran-4-ols (2) exclusively as expected. On the other hand, 1-exo isomers (exo-1) underwent a novel transformation to 1-substituted 2a-(1-arylethenyl)-1,2,2a,7b-tetrahydrocyclobuta[b]benzofurans (3), together with 2.     

Probes for narcotic receptor mediated phenomena. Part 31: Synthesis of rac-(3R,6aS,11aS)-2-methyl-1,3,4,5,6,11a-hexahydro-2H-3,6a-methanobenzofuro[2,3-c]azocine-10-ol, and azocine-8-ol, the ortho-c and the para-c oxide-bridged phenylmorphan isomers

Two of the 12 possible oxide-bridged phenylmorphans, were synthesized, rac-(3R,6aS,11aS)-2-methyl-1,3,4,5,6,11a-hexahydro-2H-3,6a-methanobenzofuro[2,3-c]azocine-10-ol (7) (the ortho-c compound), and rac-(3R,6aS,11aS)-2-methyl-1,3,4,5,6,11a-hexahydro-2H-3,6a-methanobenzofuro[2,3-c]azocine-8-ol (8) (the para-c compound). Single-crystal X-ray diffraction studies indicated that the dihedral angle between the least squares planes through the phenyl ring and the atoms C₁, C_11a, C₁₂, and C₃ in the piperidine ring in both 7·CHCl₃ and 8·HBr was 6.9°. The C₁₂-C_6a-C_6b-C_10a torsion angle was found to be 139.3° for both compounds. The angular relationship between the phenolic ring and the piperidine ring in phenylmorphans that interact with specific opioid receptors as agonists or antagonists is of considerable theoretical interest.