Curt Wentrup

α-Oxoketenes - Preparation and Chemistry

This review describes the methods of generation of alpha-oxoketenes and their use in synthesis. While the ketenes are often generated in situ without direct proof for their existence, methods used for their direct observation are also emphasized. The most important classes of precursor molecules are 2-diazo-1,3-diketones, 1,3-dioxin-4-ones, 2,3-dihydrofuran-2,3-diones, and beta-ketoacid derivatives. Synthetically useful reactions are nucleophilic additions to give carboxylic acid derivatives which can be subjected to further functional group manipulation, [2 + 2] cycloadditions to give four-membered rings, and [2 + 4] cycloaddition chemistry with a wide variety of double-and triple-bonded dienophiles, resulting in numerous six-membered heterocyclic ring systems.

Hetarylnitrenes—II : Azido/tetrazoloazine tautomerisation, and evidence for nitrene formation in the gas-phase

Abstract Azide-tetrazole tautomerism in tetrazoloazines has been examined by IR, NMR and mass spectrometry. Tetrazolo[1·5-a]pyrimidines (IV) with electron donating groups in position 5 showed no pronounced tendency to tautomerize to azides. An electron withdrawing group (Cl) in position 5, by contrast, favours the azido-form (Ve) which is a metastable solid at room temperature, rearranging to the tetrazole (IVe) at the m.p.; the azide is formed again when the tetrazote melts. In the tetrazolo[1·5-c] pyrimidine/4-azidopyrimidine series (VI-VII) the exactly opposite effect has been observed; electron donating groups in positions 5 and 7 stabilize the azido-form (VII), while in position 8 they favour the tetrazole form. Contrary to general belief, “2,4-diazidopyrimidines” exist in the 5-azido-tetrazolo [1·5-a]pyrimidine form (IVf) with the isomeric 5-azido-tetrazolo[1·5-c]pyrimidine form (VIf) as a likely minor constituent. The diazido-form (Vf) is metastable at room temperature, rearranging to the tetrazoles at the m.p. Liquid SO2 was found to be a suitable solvent for preserving individual tautomers in solution. Tetrazolopyrazine (XI) isomerizes partly to the azido-form (XII) in chloroform and trifluoacetic acid, while tetrazolo[1·5-b]pyridazine (XIII) and tetrazolo[1·5--a]pyridine (I) are completely stable in the tetrazole forms in solution and at 140°. The mass spectra of the labile tetrazoles indicate that the first step in gas-phase pyrolysis is azide-tautomerization with subsequent nitrene formation. Preparation of several tetrazolo-diazines is described.

Nitrile Imines: Matrix Isolation, IR Spectra, Structures, and Rearrangement to Carbodiimides

The structures and reactivities of nitrile imines are subjects of continuing debate. Several nitrile imines were generated photochemically or thermally and investigated by IR spectroscopy in Ar matrices at cryogenic temperatures (Ph-CNN-H 6, Ph-CNN-CH(3)17, Ph-CNN-SiMe(3)23, Ph-CNN-Ph 29, Ph(3)C-CNN-CPh(3)34, and the boryl-CNN-boryl derivative 39). The effect of substituents on the structures and IR absorptions of nitrile imines was investigated computationally at the B3LYP/6-31G* level. IR spectra were analyzed in terms of calculated anharmonic vibrational spectra and were generally in very good agreement with the calculated spectra. Infrared spectra were found to reflect the structures of nitrile imines accurately. Nitrile imines with IR absorptions above 2200 cm(-1) have essentially propargylic structures, possessing a CN triple bond (typically PhCNNSiMe(3)23, PhCNNPh 29, and boryl-CNN-boryl 39). Nitrile imines with IR absorptions below ca. 2200 cm(-1) are more likely to be allenic (e.g., HCNNH 1, PhCNNH 6, HCNNPh 43, PhCNNCH(3)17, and Ph(3)C-CNN-CPh(3)34). All nitrile imines isomerize to the corresponding carbodiimides both thermally and photochemically. Monosubstituted carbodiimides isomerize thermally to the corresponding cyanamides (e.g., Ph-N═C═N-H 5 → Ph-NH-CN 8), which are therefore the thermal end products for nitrile imines of the types RCNNH and HCNNR. This tautomerization is reversible under flash vacuum thermolysis conditions.

Nitrenes, Carbenes, Diradicals, and Ylides. Interconversions of Reactive Intermediates

Rearrangements of aromatic and heteroaromatic nitrenes and carbenes can be initiated with either heat or light. The thermal reaction is typically induced by flash vacuum thermolysis, with isolation of the products at low temperatures. Photochemical experiments are conducted either under matrix isolation conditions or in solution at ambient temperature. These rearrangements are usually initiated by ring expansion of the nitrene or carbene to a seven-membered ring ketenimine, carbodiimide, or allene (that is, a cycloheptatetraene or an azacycloheptatetraene when a nitrogen is involved). Over the last few years, we have found that two types of ring opening take place as well. Type I is an ylidic ring opening that yields nitrile ylides or diazo compounds as transient intermediates. Type II ring opening produces either dienylnitrenes (for example, from 2-pyridylnitrenes) or 1,7-(1,5)-diradicals (such as those formed from 2-quinoxalinylnitrenes), depending on which of these species is better stabilized by resonance. In this Account, we describe our achievements in elucidating the nature of the ring-opened species and unraveling the connections between the various reactive intermediates. Both of these ring-opening reactions are found, at least in some cases, to dominate the subsequent chemistry. Examples include the formation of ring-opened ketenimines and carbodiimides, as well as the ring contraction reactions that form five-membered ring nitriles (such as 2- and 3-cyanopyrroles from pyridylnitrenes, N-cyanoimidazoles from 2-pyrazinyl and 4-pyrimidinylnitrenes, N-cyanopyrazoles from 2-pyrimidinylnitrenes and 3-pyridazinylnitrenes, and so forth). The mechanisms of formation of the open-chain and ring-contraction products were unknown at the onset of this study. In the course of our investigation, several reactions with three or more consecutive reactive intermediates have been unraveled, such as nitrene, seven-membered cyclic carbodiimide, and open-chain nitrile ylide. It has been possible in some cases to observe them all and determine their interrelationships by means of a combination of matrix-isolation spectroscopy, photochemistry, flash vacuum thermolysis, and computational chemistry. These studies have led to a deeper understanding of the nature of reactive intermediates and chemical reactivity. Moreover, the results indicate new directions for further exploration: ring-opening reactions of carbenes, nitrenes, and cyclic cumulenes can be expected in many other systems.

THERMOCHEMISTRY OF CARBENE AND NITRENE REARRANGEMENTS

Abstract Thermochemical estimates for aromatic carbenes and nitrenes and their interconversions are reported and allow a unifying explanation of the majority of the experimental data published to date. Chemical activation is a very important, but hitherto ignored factor in these rearrangements. This has given rise to several misinterpretations in the literature, which are now corrected.

Carbenes and Nitrenes in Heterocyclic Chemistry: Intramolecular Reactions

Publisher Summary The chapter reviews the literature of carbenes and nitrenes. It accounts for vinylnitrenes, 2H-azirines, iminocarbenes, imidoylcarbenes, 1H-azirin, oxocarbenes, oxiren, thioxocarbenes, thiirenes, selenium analog, acylnitrenes and Thio Analogs, and imidoylnitrenes and nitrilimines (Azocarbenes). The chapter discusses arylcarbenes and arylnitrenes wherein mechanism of carbine–nitrene rearrangements, matrix photochemistry, formations of azepines, o-Diamines, and pyridines are also discussed. Cyclization onto an adjacent ring is done in two ways: direct cyclization and carbine–carbene and carbine–nitrene rearrangement. Cyclization between bridged rings are carried out for methylene bridging group, sulfur bridging group, and O,N, SO2, or CO bridging groups. Undoubtedly there are still innumerable arrangements and synthetic application of carbenes and nitrenes to be discovered. This together with the flourishing chemistry of silylenes and the emerging chemistry monovalent boron and phosphorous compounds give the entire field of electron-deficient reactive intermediates enormous synthetic potential.

The Benzyne Story

The history of o-benzyne from its early beginnings as an unobservable reactive intermediate until its present status as a very well characterized but still theoretically challenging molecule with important applications in synthesis is reviewed. The m- and p-benzynes, tridehydrobenzenes, and benzdiynes are also known, and p-benzyne is a key intermediate in the action of a potent class of ene-diyne anti-tumour compounds.

Formation of Cumulenes, Triple-Bonded, and Related Compounds by Flash Vacuum Thermolysis of Five-Membered Heterocycles

Flash vacuum thermolysis of a large variety of heterocyclic compounds is a useful means of production of ketenes, ketenimines, thioketenes, allenes, iminopropadienones, bis(imino)propadienes, iminopropadienethiones, carbodiimides, isothiocyanates, acetylenes, fulminic acid, nitrile imines and nitrile ylides, nitriles, cyanamides, cyanates, and other compounds, often in preparatively useful yields.

Flash Pyrolysis of 4‐Arylmethylidene‐oxazolones and ‐isoxazolones. A Versatile Synthesis of Arylacetylenes. Preliminary communication

Flash pyrolysis of 4-benzylidene-2-phenyl-5(4H)-oxazolone (1) yields carbonmonoxide, benzene, biphenyl, diphenylacetonitrile, and 2,3-diphenylsuccinonitrile; N-benzoylphenylketenimine is implicated as the primary intermediate. The flash pyrolysis of 4-arylmethylidene-3-methyl-5(4H)-isoxazolones (3) yields carbon dioxide, acetonitrile, and phenylacetylenes substituted by alkoxy, chloro, dimethylamino, and hydroxy groups, in yields of 45–95%. Arylmethylidenecarbenes are implicated as intermediates.

Hetarylnitrenes—I : Ring contraction and fragmentation in nitrenodiazines

Abstract Gas-phase thermolysis of tetrazolo[1.5-a]pyrimidines gives 1-cyanopyrazoles by ring contraction and 2-aminopyrimidines by H-abstraction. Tetrazolo[1.5-c]pyrimidines give 1-cyanoimidazoles; 1-cyanoimidazole similarly results from pyrolysis of tetrazolo[1.5-c]pyrazine. Tetrazolo[1.5-b]pyridazine lose two molecules of N2 to form C4H3N, which isomerizes to cyanoallene, tetrolonitrile, propargyl cyanide and 2-cyanocyclopropene. It is concluded that 2-pyrimidylnitrene and 3-pyridazinylnitrene do not interconvert on the C4H3N3 energy surface via ring expansion.