N-Vinyl- and C-vinylpyrroles from azafulvenium methides. flash vacuum pyrolysis route to 5-Oxo-5H-pyrrolizines and 1-azabenzo[f]azulenes

1-Azafulvenium methides, generated from pyrrolo[1,2-c]thiazole-2,2-dioxides' thermal extrusion of sulfur dioxide, led to the synthesis of functionalized pyrroles. The intramolecular trapping of these transient 8pi 1,7-dipoles in pericyclic reactions, namely sigmatropic [1,8]H shifts and 1,7-electrocyclization, allowed the synthesis of N-vinylpyrroles and C-vinylpyrroles which, under flash vacuum pyrolysis conditions, are converted into 5-oxo-5H-pyrrolizines or 4-oxo-1,4-dihydro-1-aza-benzo[f]azulenes, respectively. These heterocycles can also be obtained directly from FVP of pyrrolo[1,2-c]thiazole 2,2-dioxides. The synthesis and X-ray structure of a new 6-oxocyclopenta[b]pyrrole derivative is also reported.     

Interconversions of aryl radicals by 1,4-shifts of hydrogen atoms. A synthesis of benzo[a]corannulene

Aryl radicals generated ortho to aryl substituents by flash vacuum pyrolysis (FVP) of the corresponding aryl chlorides are shown to be capable of transferring hydrogen atoms between the ortho and ortho' positions (1,4-shifts of hydrogen atoms). In the examples described here, the rearranged aryl radicals are trapped by subsequent radical cyclization reactions. For example, FVP of 2-(o-chlorophenyl)benzo[c]phenanthrene gives 1-phenylbenzo[ghi]fluoranthene as the major product by homolysis of the C-Cl bond, 1,4-shift of a hydrogen atom out of the sterically congested cove region to the radical center, cyclization of the rearranged radical, and rearomatization of the molecule by loss of the other cove region hydrogen. In a control experiment run under the same conditions, FVP of 2-phenylbenzo[c]phenanthrene, which lacks a radical precursor, gave primarily recovered starting material. When the FVP was repeated using 2-(2,6-dichlorophenyl)benzo[c]phenanthrene as the starting material, benzo[a]corannulene was obtained as the major product, presumably by the same cascade of events to produce 1-(o-chlorophenyl)benzo[ghi]fluoranthene, which then suffers a second radical cyclization spontaneously under the high-temperature conditions to give the geodesic polyarene.     

Temperature dependent NMR spectra of oxazepines,thiazepines, oxazocines and thiazocines

The temperature dependence of several 7-membered 5-substituted-5,11-dihydrodibenz[b,e] [1,4]oxazepines (Z = O) and thiazepines (Z = S), as well as of 8-membered 12-substituted -6,11-dihydro-12H-dibenz[b,f] [1,4]oxazocines (Z = O) and thiazocines (Z = S), has been studied by NMR spectroscopy. The average ΔF* (kcal/mol) values at coalescence temperatures are 14·0 (M = CHO), 18·2 (M = COCH₃) for oxazepines, 17·3 (M = CHO), >21 (COCH₃) for thiazepines, and 13·0 for oxazocines and 13·3 for thiazocines, respectively. These data show that replacement of oxygen by a sulfur atom raises the barrier height of ring inversion, but that this effect is greater with the 7-membered than with 8-membered heterocycles. Thus the 8-membered rings have a greater degree of flexibility than do the 7-membered ones. With the oxazepines and the thiazepines, it was also possible to measure the thermodynamics (ΔF*, ΔH* and ΔS*) of the hindered rotation around the N? CO bond by studying the temperature dependence of the formyl and acetyl proton resonances. The results suggest that the processes of conformational inversion and hindered rotation in the same molecule are independent of each other. The rate of hindered rotation is slower than the rate of conformational inversion. The conformational preferences of the compounds are also discussed.     

Thermal ring contraction of dibenz[b,f]azepin-5-yl radicals: new routes to pyrrolo[3,2,1-jk]carbazoles

Flash vacuum pyrolysis (FVP) of N-allyl- or N-benzyldibenz[b,f]azepine at temperatures from 750 to 950 degrees C gives pyrrolo[3,2,1-jk]carbazole as the major product. The mechanism of the ring contraction involves dibenzazepin-1-yl radical formation, followed by transannular attack and formation of a 2-(indol-1-yl)phenyl radical which cyclizes. The mechanism is supported by independent generation of 2-(indol-1-yl)phenyl radicals by two different methods, and the use of 1-(2-nitrophenyl)indole as a radical generator gives an optimized synthetic route to pyrrolo[3,2,1-jk]carbazole (54% overall yield in two steps from indole). The first substituted pyrrolo[3,2,1-jk]carbazoles have been synthesized by FVP methods and also by reactions of the parent compound with electrophiles, leading to a range of 4-substituted pyrrolocarbazoles.     

Synthesis of N-heterocycles via [4 + 3] cycloaddition of azomethine imine

Di, tri and tetra-nitrogen containing 7-membered heterocycles are the key building blocks for natural and medicinally active compounds. They are using as antidepressants, antiulcer, antibiotics, antiemetic and also used as herbicides and insecticides. These building blocks can be synthesized easily from [4 + 3] cycloadditon reaction of azomethine imine with the other suitable reacting partner. Research on this area is very much important as this area is not much explored till now. Hence, the synthetic literature survey towards the di-nitrogen containing heterocycles is paramount importance. Herein, we report numerous synthetic routes (metal catalyzed, metal free, asymmetric) of di-nitrogen containing 7-membered heterocycle through [4 + 3] cycloadditon reaction of the last 10 years (2011-2019).     

Reaction of tetraazathiapentalene and thiadiazolopyrimidine derivatives with heterocumulenes: Cycloaddition and elimination reactions via hypervalent sulfur intermediates

Tetraazathiapentalene derivative 1 reacts with heterocumulenes such as diphenylketene (2) and 2‐pyridylisothiocyanate (5) to give heterocycles 3, 6 and 7 with elimination of methylisothiocyanate. The reactions of thiadiazolopyrimidine derivatives 8a‐b with ethoxycarbonyl isothiocyanate (9) and carbon disulfide (11) gives heterocycles 10 and 12 via thermal decomposition of 1:1 cycloadducts C and D which have a hypervalent sulfur. The mechanistic and reactivity features of these reactions are described.     

有机磷杂环化合物研究(Ⅷ)──Lawesson试剂与合两个氨基的底物的成环反应

研究Lawesson试剂与含有两个氨基的底物的成环反应,合成了N-P-N型五元、六元磷杂环3a-3b、sa－5b及8a－8b,并讨论了成环机理．初步的生测结果表明,所合成的磷杂环具有一定的除草活性,因此LR的成环反应是合成具有生物活性的磷杂环的新方法．     

Phenyl migrations in dehydroaromatic compounds. A new mechanistic link between alternant and nonalternant hydrocarbons at high temperatures

Flash vacuum pyrolysis of benzo[b]biphenylene, an alternant polycyclic aromatic hydrocarbon (PAH), gives fluoranthene, a nonalternant PAH, as the major product at 1100 degrees C in the gas phase. The most reasonable mechanism to explain this isomerization involves equilibrating diradicals of 2-phenylnaphthalene that rearrange by the net migration of a phenyl group to give equilibrating diradicals of 1-phenylnaphthalene, one isomer of which then cyclizes to fluoranthene.     

Resolution of benzo[a]pyrene in complex mixtures of other polycyclic aromatic hydrocarbons. Comparison of two spectrofluorimetric methods applied to water samples

Two spectrofluorimetric methods, second-derivative constant-energy synchronous luminescence (SDCESL) and constant-wavelength synchronous luminescence (CWSL) in combination with multiple linear regression (MLR), for the quantification of benzo[a]pyrene (BaP) at sub-ng mL-1 levels, in the presence of benzo[b]fluoranthene (BbFt), benzo[k]fluoranthene (BkFt), benzo[ghi]perylene (BghiP) and indeno[1,2,3-cd]pyrene (IP), were developed and compared in detail. SDCESL presents lower limits of detection and quantification than CWSL/MLR and also gives more exact and precise results for levels close to the quantification limit. For BaP, SDCESL achieved quantification limits of 0.019 ng mL-1 in river waters and 0.007 ng mL-1 in drinking waters. This work offers a sensitive, precise, accurate, rapid, simple and economic methodology for monitoring BaP in waters for public consumption, meeting all the requirements of the EC Directive 98/83/CE that fixes the maximum admissible limit for this polycyclic aromatic hydrocarbon in drinking waters at of 0.010 ng mL-1.     

A thermal cascade route to pyrroloisoindolone and pyrroloimidazolones

Flash vacuum pyrolysis (FVP) of indol-1-ylacrylate derivatives 11 and 15 or the isomeric indol-3-ylacrylates 21, 22, and 24 at 925 degrees C (0.05 Torr) provides pyrrolo[1,2-a]indol-3-ones 2, 18, 28, and 29 in 53-90% yield by a cascade mechanism that involves a sigmatropic migration, elimination, electrocyclization sequence. Pyrrolo[1,2-a]imidazol-5-ones 3 and pyrrolo[1,2-c]imidazol-5-ones 4 were similarly obtained by FVP of corresponding 2,5-unsubstituted imidazol-1-ylacrylates (e.g., 33), with the former isomer predominating in ca. 80:20 ratio. Migration to the 2-position is therefore favored in the initial sigmatropic shift. FVP of 2-substituted imidazol-1-ylacrylates 35, 37, and 51 (825-875 degrees C) instead give pyrrolo[1,2-c]imidazol-5-ones 56-58 only (88-91%), and that of 4,5-disubstituted imidazol-1-ylacrylates 39 and 41 (825-850 degrees C) provide pyrrolo[1,2-a]imidazol-5-ones 59 and 60 exclusively (93-95%), and thus the selectivity of the initial shift can be controlled by the presence of substituents on the imidazole 2- and 5-positions. FVP of the benzimidazole analogues 61 and 62 at 950 degrees C gave the pyrrolo[1,2-a]benzimidazol-1-ones 6 (71%) and 63 (36%), respectively.     

Isoindolo[2,1-a]indol-6-one--a new pyrolytic synthesis and some unexpected chemical properties

Isoindolo[2,1-a]indol-6-one 1 is formed by a sigmatropic shift-elimination-cyclisation cascade by flash vacuum pyrolysis (FVP) of methyl 2-(indol-1-yl)benzoate 7 at 950 degrees C. The dihydro compound 16 is easily obtained by catalytic reduction of 1, but the reaction is very sensitive to steric effects at the 11-position. Attempted ring-opening of 1 in basic methanol provides an equilibrium of isoindolo[2,1-a]indol-6-one 1 and the ester 19. Lithium aluminium hydride reduction of 1 provides the alcohol 22 which can be dehydrated to a mixture of 23 and 24 by FVP at 800-950 degrees C.     

Synthesis and analgesic activity of novel heterocycles, [1]benzothiopyrano[3,4-b]pyrrole derivatives

In order to develop analgesic compounds possessing a sulfur atom in the alicyclic ring, novel cis-fused heterocycles, [1]benzothiopyrano[3,4-b]pyrrole derivatives (II) were synthesized via a unique cyclization reaction starting from 4-(4-methoxyphenylthio)-2-butanone (1) or 6-methoxy-3,4-dihydro-2H-1-benzothiopyran-4-one (7). The analgesic effects of benzothiopyranopyrroles (16, 18) were measured by means of the writhing test. The phenolic derivative 18 completely inhibited the appearance of writhing at the dose of 50 mg/kg, but the methoxy derivative 16 had no analgesic effect.     

Synthesis of isoindolo[2,1-a]quinoline derivatives and their effects on N2-induced hypoxia

A variety of isoindolo[2,1-a]quinoline derivatives as well as the following related heterocycles have been prepared: 11b,12-dihydro-5H-isoindolo[2,1-b][2]benzazepine-7,13-dione (8a), 7,8,14,14a-tetrahydroisoindolo[2,1-c][3]benzazocine-5, 13-dione (8b), 6a,7-dihydroisoquinolino[2,3-a]quinoline-5,12-dione (12), 2,3,3a-4-tetrahydropyrrolo[1,2-a]quinoline-1,5-dione (14), and pyrido[2',3':3,4]pyrrolo[1,2-a]quinoline-5,11(5H)-dione (17). The key synthetic step involves an intramolecular Friedel-Crafts reaction of acid chlorides such as isoindole-1-acetyl chlorides (4), the acids (3) of which were prepared starting with 2-arylisoindole-1,3(2H)-diones (2-arylphthalimides) (1). The protective effects of isoindolo[2,1-a]quinoline derivatives (19 and 20) against N2-induced hypoxia were examined. Among them, 6-(diethylaminomethyl)isoindolo[2,1-a]quinoline-5,11(5H)-dio ne (19b) showed the most potency.     

Rack-mounted chemistry IV: the thermal rearrangement of 7-oxabenzonorbornadienes into benzo[b]oxepines on and off the polycyclic rack

The thermal rearrangement of [3]polynorbornane bis-imide rack-mounted 7-oxabenzonorbornadienes has been conducted using flash vacuum pyrolysis (FVP) at 520 °C and is compared with the FVP of similar 7-oxabenzonorbornadienes off the rack. The isomerisation is considered to involve (a) C–O bond cleavage to a vinylogous 1,5-dipole, (b) formation of a benzene epoxide by nucleophilic ring-closure and (c) valence-isomerisation of the benzene epoxide to the oxepine. Competing fragmentation to the isobenzofuran by ejection of acetylene and other rearrangements become prominent pathways off the rack, whereas isomerisation to the oxepine is highly favored on the rack.     

The intramolecular sila-Pummerer cyclization: A new route to sulfur heterocycles

The generality of the intramolecular cyclization of suitable nucleophilic sites to a  S⁺CH₂ center created by a sila-Pummerer rearrangement has been investigated. Successful nucleophilic sites included the OH group (in alcohols, carboxylic acids, and hydroxylamines) and the NH group (in amines and carbamates): attempts to produce carbon-based nucleophilic sites were not effective. Successful cyclizations were achieved to produce sulfur heterocycles with 5-, 6-, and 7-membered rings.     

Cyclocondensation of 4-hydroxy-5,6-diaminopyrimidine with α,β-dihalochalcones

The condensation of 4-hydroxy-5,6-diaminopyrimidine with 1,3-diaryl-2,3-dihalopropanones and with dibenzoylacetylenes was used to obtain derivatives of 1H-pyrimido[4,5-b]-1,5-diazepine and pyrimido[4,5-b]pyrazine, respectively. Their spectral characteristics were studied, and the directions in the formation of 7- and 6-membered heterocycles were determined. The synthesized pyrimido[4,5-b]pyrazines exist in the form of two tautomeric species — enaminocarbinol and enol forms, with an intramolecular hydrogen bond of the chelate type.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1409–1414, October, 1993.     

Utilization of 2‐Chloronicotinonitrile in the Syntheses of Novel Fused Bicyclic and Polynuclear Heterocycles of Anticipated Antitumor Activity

Some of synthetic bicyclic and polynuclear heterocyclic compounds based on pyridine scaffold were tested as in vitro antitumor agents, and these compounds found to exhibit interesting activities. Fused heterocycles containing sulfur such as thienopyridine, pyridothiazine, and some related fused heterocycles as new ring systems were achieved. Bicyclic thienopyridine 6 and pyrido[3,2‐e][1,3]thiazin‐4(3H)‐one 7 exhibited good antitumor activities compared with 5‐fluorouracil.     

Synthesis and structure of a novel molybdenum imido calix[6]arene

Treatment of p-tert-butylcalix[6]areneH₆ (H₆L) with [Mo(OBu^t)₂{[2,2′-(N)-C₆H₄]₂(CH₂CH₂)}] in refluxing toluene affords, after work-up, the complex [Mo(2-NC₆H₄CH₂CH₂C₆H₄NHC(Me)NH-2^/)LH₂]·4MeCN (1), which contains an 11-membered metallocyclic ring as characterised by Synchrotron X-radiation.     

A synthesis of heteroaromatic analogues of 1-methyl-1,2,3,4-tetrahydroisoquinoline using the Pummerer-type cyclization reaction: observation of tandem cyclization reaction

The sulfoxides 7b and 7d carrying thiophene or benzothiophene as heteroaromatic nucleophiles, when treated with trifluoroacetic anhydride at room temperature (Pummerer reaction), underwent an intramolecular alkylation in an exclusive manner to yield 4,5,6,7-tetrahydro-7-methyl-4-phenylsulfanylthieno[2,3-c]pyridine-6-carbaldehyde (10) and the corresponding benzothiophene derivative (12b) in high yields, respectively. Thus, this route provides biologically interesting nitrogen heterocycles (1b) and (2b). On the other hand, the sulfoxide (7c) carrying benzofuran as a nucleophile on reaction with TFAA yielded not only the Pummerer-type cyclization product (12a), but also the diastereoisomeric tandem cyclization products (13) and (14) having a noble 11-aza-2-oxa-7-thiatricyclo[4.3.3.0(1,5)]dodecane ring system (B). The formation of these products can be readily rationalized by the intervention of the oxonium ion intermediate (21).     

A new and simple method for the synthesis of highly functionalised pyrrolizidines, indolizidines and pyrroloazepines

The reaction of 5-, 6- and 7-membered cyclic thioimidates with cyclopropenones gives access to highly functionalised pyrrolizidines, indolizidines and pyrroloazepines via a formal [3+2] cycloaddition process.