The 3,3'-pyrrolidinyl-spirooxindole unit is a privileged heterocyclic motif that forms the core of a large family of alkaloid natural products with strong bioactivity profiles and interesting structural properties. Significant recent advances in the synthesis of this fused heterocyclic system have led to intense interest in the development of related compounds as potential medicinal agents or biological probes.

Pyrrolidinyl-spirooxindole natural products as inspirations for the development of potential therapeutic agents.

Construction of Spiro[pyrrolidine‐3,3′‐oxindoles] − Recent Applications to the Synthesis of Oxindole Alkaloids

Isolation and synthesis of biologically active carbazole alkaloids

Two-dimensionally extended, polycyclic heteroaromatic molecules (heterocyclic nanographenes) are a highly versatile class of organic materials, applicable as functional chromophores and organic semiconductors. In this Review, we discuss the rich chemistry of large heteroaromatics, focusing on their synthesis, electronic properties, and applications in materials science. This Review summarizes the historical development and current state of the art in this rapidly expanding field of research, which has become one of the key exploration areas of modern heterocyclic chemistry.

Heterocyclic Nanographenes and Other Polycyclic Heteroaromatic Compounds: Synthetic Routes, Properties, and Applications

2.5. Ionic Liquids Presented in This Review 2020 3. Cyclocondensation Reactions 2020 4. Synthesis of Three-Membered Heterocycles 2022 4.1. Aziridines 2022 5. Synthesis of Five-Membered Heterocycles 2022 5.1. Pyrroles 2022 5.2. Furans 2022 5.3. Thiophenes 2023 5.4. Pyrazoles 2024 5.5. Imidazoles 2025 5.6. Isoxazoles 2027 5.7. Oxazoles, Oxazolines, and Oxazolidinones 2027 5.8. Thiazoles and Thiazolidinones 2028 6. Synthesis of Six-Membered Heterocycles 2030 6.1. Pyridines 2030 6.2. Quinolines 2031 6.3. Acridines 2033 6.4. Pyrans 2033 6.5. Flavones 2035 6.6. Pyrimidines and Pyrimidinones 2035 6.7. Quinazolines 2037 6.8. -Carbolines 2038 6.9. Dioxanes 2039 6.10. Oxazines 2039 6.11. Benzothiazines 2040 6.12. Triazines 2040 7. Synthesis of Seven-Membered Heterocycles: Diazepines 2041

Ionic liquids in heterocyclic synthesis.

Oxidation of 2,2,5-trimethyl-5-phenylseleno-1,3-dioxan-4,6-dione with m-chloroperbenzoic acid in methylene chloride gives a solution containing 2,2-dimethylspiro[1,3-dioxan-5,2'-oxiran]-4,6-dione and the unstable 2,2-dimethyl-5-methylene-1,3-dioxan-4,6-dione, which forms stable adducts with cyclohexadiene and cyclopentadiene. Flash vacuum pyrolysis of the cyclopentadiene adduct over the temperature range 460- 570° and detection of the components present in the pyrolysate by mass spectrometry showed that cyclopentadiene, acetone, carbon dioxide and methyleneketene (CH2=C=C=O) are formed; the last breaks down into acetylene and carbon monoxide at higher temperatures (520-570°). Infrared measurements on the pyrolysis products kept at liquid nitrogen temperature showed absorption near 2100 cm-1 which is attributed to methyleneketene. Reaction of the pyrolysate with aniline vapour or methanol vapour yielded acrylanilide and methyl acrylate respectively. Pyrolysis in the absence of trapping agents gave a glassy solid on an uncooled glass surface. This solid is considered to be formed by addition of methyleneketene to 2,2-dimethyl-5-methylene-1,3-dioxan-4,6- dione. Methanolysis of the solid and esterification with diazomethane gave dimethyl 2-methoxycarbonyl-4-methylenepentanedioate.

Methyleneketenes and methylenecarbenes. VII. Evidence for the pyrolytic generation of methyleneketene (propadienone)

Flash vacuum pyrolysis (430°) of 5-benzylidene-2,2-dimethyl-1,3-dioxan- 4,6-diones gives benzylidene-ketenes which dimerize to form 2,4- bis(benzylidene)cyclobutane 1,3-diones. Diphenylmethylene-,t- butylmethylene- and isopropylidene-2,2-dimethyl-1,3-dioxan-4,6-diones similarly give the substituted methylene ketenes which dimerize to form 2,4-bis(diphenylmethylene)-, 2,4-bis(t-butylmethylene)- and 2,4- bis(isopropylidene)-cyclobutane-1,3-dione respectively. Infrared measurements on the pyrolysis products kept at liquid nitrogen temperature showed absorption near 2100 cm-1 which was attributed to the methyleneketenes. Reaction of the pyrolysates of ethylidene- and isobutylidene-2,2-dimethyl-1,3-dioxan-4,6-diones with aniline vapour yielded but-3-enanilide and 4-methylpent-3-enanilide respectively.

Methyleneketenes and methylenecarbenes. I. Formation of arylmethyleneketenes and alkylideneketenes by pyrolysis of substituted 2,2-Dimethyl-1,3-dioxan-4,6-diones

Flash vacuum pyrolysis of 1-(1?-adamantyl)acetylene[2-14C] (780°) gives recovered alkyne which contains 25% of the rearranged product, 1-(1?- adamantyl)acetylene[1-14C]. 1-Ethynyl-1-methylcyclohexane(740°) is converted into toluene and benzene, while evidence for rearrangement of 3,3-dimethylbut-1-yne[2-13C] (790°) and 3-methyl-3-phenylbut-1-yne[2- 13C] (680°) was not obtained before the onset of alternative reactions. These reactions of alkyl-substituted alkynes are discussed in terms of possible methylene carbene intermediates. Similar intermediates may possibly be involved in reactions of arylalkynes. Thus, pyrolysis of 1- ethynylnaphthalene (750°) yields acenaphthylene and of 1-ethynyl-8- methylnaphthalene (750°) yields phenalene. The pathways for the formation of 2-phenyl- and 3-phenyl-indene from (2- methylphenyl)phenylethyne (790°) and of indene from (2- methylphenyl)ethyne (740°) are obscured by facile thermal rearrangements.

Methyleneketenes and methylenecarbenes. IX. Thermal rearrangements of Alkyl-and Aryl-acetylenes involving Alkyl- and Aryl-methylenecarbenes

Cyclopent[a]indene (benzopentalene) : generation by flash vacuum pyrolysis and subsequent dimerisation.

Examination of [13C2]biphenylene formed by gas phase pyrolysis of doubly labelled benzyne precursors shows that the principal pyrolytic process leads to overall 1,2→1,3 rearrangement of the C6H4 carbon skeleton either in an intermediate C7H4O before decarbonylation or in benzyne itself. A minor process involves an apparent 1,3-hydrogen shift. [1,2-13C2]Ethyne-1,2-diylbistrimethylsilane was acylated with 3-(2,5-dihydro-1,1-dioxothien- 2-yl)propanoyl chloride and the resulting ketone was desilylated to yield 5-(2,5-dihydro-1,l-dioxo-thien-2-yl)[1,2-13C2]pent-1-yn-3-one. Thermal elimination of sulfur dioxide and cyclization followed by dehydrogenation yielded [7,7a-13C2]-2,3-dihydro-1H-inden-1-one which was oxidized and dehydrated to give [3a,4-13C2]isobenzofuran-1,3-dione. This doubly labelled phthalic anhydride was diluted to approximately 5% 13C2 and the resulting material was converted via benzenediazonium- 2-carboxylate into biphenylene at 84o, and pyrolysed at 830o to yield biphenylene, and a sample diluted to 7.5% was converted into [2a,3-13C2]benzocyclobutenedione which was pyrolysed at 650o, 750o and 830o to yield further samples of biphenylene. The biphenylene samples were examined by mass spectrometry at 20 eV to determine their isotopic composition and by 13C n.m.r. spectroscopy to determine the distribution of labelling.

Observation of 13C rearrangement in [13C2] biphenylene formed from benzyne on pyrolysis of [1,6-13C2] phthalic anhydride and [2a,3-13C2]-benzocyclobutenedione

Frank W. Eastwood

Papers

Methyleneketenes and methylenecarbenes. VII. Evidence for the pyrolytic generation of methyleneketene (propadienone)

Methyleneketenes and methylenecarbenes. I. Formation of arylmethyleneketenes and alkylideneketenes by pyrolysis of substituted 2,2-Dimethyl-1,3-dioxan-4,6-diones

Methyleneketenes and methylenecarbenes. IX. Thermal rearrangements of Alkyl-and Aryl-acetylenes involving Alkyl- and Aryl-methylenecarbenes

Cyclopent[a]indene (benzopentalene) : generation by flash vacuum pyrolysis and subsequent dimerisation.

Observation of 13C rearrangement in [13C2] biphenylene formed from benzyne on pyrolysis of [1,6-13C2] phthalic anhydride and [2a,3-13C2]-benzocyclobutenedione