Synthesis of Benzodiazepines Through Ring Opening/Ring Closure of Benzimidazole Salts

Pyrido-benzodiazepine derivatives are undoubtedly one of the most important structural motifs in the marketed drugs and the drug candidates. Commonly synthetic methods for construction of the benzodiazepine ring derivatives are based on the condensation reactions of two highly functionalized synthons. The development of synthesis for these compounds, however, is hampered by the regioselectivity and atom economy. In this work, a one-step synthesis of pyrido-benzodiazepine backbones and its analogues is achieved through continuous ring-opening hydrolysis of benzimidazole salts and intramolecular C−H bond activation. The reaction mechanism is explored by control experiments and density functional theory (DFT) calculations.     

氧杂环丁烷的扩环反应

氧杂环丁烷是一类重要的小杂环化合物,也是重要有机合成中间体,在有机化学、药物化学和高分子化学中都有广泛的应用.作为具有较大环张力的小杂环化合物,氧杂环丁烷类化合物除可以发生开环反应外,也很容易发生扩环反应,构建含氧普通环到大环化合物.主要总结了氧杂环丁烷的扩环反应,包括重氮化合物作为卡宾前体与氧杂环丁烷的扩环反应、金属...     

Ring Enlargement of N-Heterocycles

This review describes our preliminary results of ring enlargement of N-heterocycles by N-ylide formation at a targeted site, exemplified by 55→56→58. Before development of this method, the strategy can be traced to our modified Hofmann degradation led at first to several miscarried probings on the reaction between N-halomethyl ammonium salts and halophilic reagents.     

A Facile Ring Enlargement

A series of functionalized seven to eight membered rings was prepared by a ring expansion technique involving intramolecular aldol condensation and subsequent retro-aldol cleavage.     

Ring opening of thietane

The reaction of aromatic and heterocyclic carboxylic acid chlorides with thietane yields 3-chloropropylthioesters of these acids. The presence of electron-accepting substituents in the carboxylic acid chloride results in the formation of a mixture of polymeric products.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 597–598, May, 1971     

Ring inversion in fluoro-cyclohexanes

Rates of ring inversion in some isomeric octa- and deca-fluorocyclohexanes and in perfluorocyclohexane have been determined by dynamic ¹⁹FNMR spectroscopy and compared with data for other compounds. ΔG²_cb varies over the range 39–49 kJ mol^-1. Surprisingly the barriers in the diastereomeric octafluorocyclohexanes lie at opposite ends of the range. It seems that 1,3-diaxal interactions are less important than supposed hitherto; other factors which may affect the barriers are discussed.     

Ring opening in methylenecyclopropane

The indo molecular orbital calculations on methylenecyclopropane show that the ¹A₁ state of the (90,90) configuration is the most stable one at θ = 64°. The ground state of the ring-opened trimethylenemethane is predicted to be the ³A'₂ state (D_3h symmetry), however the³A″ state of non-planar (0,90) trimethylenemethane is about 10 kcal/mole higher in energy than the planar diradical species. This suggests intermediacy of the orthogonal diradical in the degenerate thermal rearrangement of substituted methylenecyclopropane. The calculated geometry, dipole moment of methylenecyclopropane, and spin densities of trimethylenemethane are in excellent agreement with the experimental values.     

Ring Enlargement of Alkaloids

Previouspublications'fromourlaboratoryhadreportedtheringenlargementreactionofquatemaryarnrnoniumsaltSofN-methyl-tetTahydroisoquinolinefollowedbyreductivedecyanationwiththenetresuItoftheinserti0nofanextraCH2group,assh0wninSckemeI.ThemethodologyfailedwithsomenatUrallyoccurringalkaloidssuchascephalotaxineandatropine'.Onereasonisthatsomeofthequaternaryammoniumsaltsaredifficulttoprepare,theotheroneisthatsome0fthequaternaryafnmoniumsaItsunderwentHofinarineliminationorSofnmeletrearrangement'.But…     

Ring Expansion Strategies for the Synthesis of Medium Sized Ring and Macrocyclic Sulfonamides

Two new ring expansion strategies are reported for the synthesis of medium sized ring and macrocyclic sulfonamides. Both methods can be performed without using classical protecting groups, with the key ring expansion step initiated by nitro reduction and amine conjugate addition respectively. Each method can be used to make diversely functionalised cyclic sulfonamides in good to excellent yields, in a range of ring sizes. The ring size dependency of the synthetic reactions is in good agreement with the outcomes modelled by Density Functional Theory calculations.     

Noble Gas in a Ring

We have designed a new type of molecule with a noble gas (Ng = Kr and Xe) atom in a six-membered ring. Their structures and stability have been studied by density functional theory and by correlated electronic structure calculations. The results showed that the six-membered ring is planar with very short Ng–O and Ng–N polar covalent bonds. The calculated energy barriers for all the unimolecular dissociation pathways are higher than 20 and 35 kcal/mol for Ng = Kr and Xe, respectively. The current study suggests that these molecules and their derivatives might be synthesized and observable at cryogenic conditions.     

Ring test for ferrous ions

Summary When ethyl alcohol is added to an aqueous solution containing small amount of pantothenic acid, ascorbic acid and Fe(II), beautiful blue ring is formed at the junction of ethyl alcohol-water which is characteristic of ferrous ions. The visual limit of identification is 25 per ml of Fe(II). The maximum tolerable limit of various metal ions which do not interfere with the formation of blue ring is reported.

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Zusammenfassung Überschichtet man eine wäßrige Lösung von Pantothensäure, Ascorbinsäure und Eisen(II) mit Äthylalkohol, so entsteht an der Berührungsstelle der beiden flüssigen Phasen ein blauer Ring, der für Eisen (II) charakteristisch ist. Die Nachweisgrenze beträgt 25 Fe(II)/ml. Für verschiedene störende Metallionen wird die maximal tolerierbare Menge angegeben.

     

Ring cleavage rearrangement of cyclobutylmethylboranes

Boranes derived from hydroboration of methylenecyclobutane with borane/THF, 9-borabicyclo[3.3.1]nonane, and borane-methyl sulfide rearranged on heating in situ at 100–160°C to open chain structures. Products after oxidation were the unrearranged cyclobutylmethanol, and 4-penten-1-ol, 1,4-pentanediol and 1,5-pentanediol. The unsaturated alcohol was the major product in reactions with a stoichiometric ratio of alkene to BH bonds, and the diols were formed with excess borane. With borane-methyl sulfide as hydroborating reagent, the rate of rearrangement at 100°C in triglyme was not significantly dependent upon the initial alkene/borane ratio $\text{3}\text{1}$ or $\text{1.15}\text{1}$ or the presence of excess methyl sulfide. However, an equivalent amount of pyridine prevented rearrangement. Rearrangement in THF using borane/THF also occurred at comparable rates in the presence and absence of excess borane. Little or no isomerization of the boron function into the cyclobutane ring was observed. Results are interpreted on the basis of a concerted four-center mechanism which requires a vacant boron orbital.     

Ring open analogues of deoxynucleotides

The synthesis of acyclic analogues of 2′-deoxyadenosine and 2′-deoxythymidine which lack only the 2′-CH₂ of the sugar is described. The synthesis of dinucleotides from these analogues is also described.