- Metal-free regioselective hydrochlorination of unactivated alkenes via a combined acid catalytic system
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A combined acid HCl/DMPU-acetic acid catalytic system was used in the hydrochlorination of a wide range of unactivated alkenes. This hydrochlorination strategy is remarkably greener than previous reported methods in terms of high atom efficiency, no toxic waste generated and metal-free process. The higher efficiency, compared with other commercially available HCl reagents, was augmented by the good regioselectivity and functionality tolerance found. A stepwise mechanism for this hydrochlorination process was proposed based on kinetic studies.
- Liang, Shengzong,Hammond, Gerald B.,Xu, Bo
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supporting information
p. 680 - 684
(2018/02/14)
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- Silica gel-mediated hydrohalogenation of unactivated alkenes using hydrohalogenic acids under organic solvent-free conditions
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Silica gel-mediated hydrochlorination of unactivated alkenes using 35% hydrochloric acid under organic solvent-free conditions proceeded to give the corresponding chlorides in good yields. Hydrobromination or hydriodination using 47% hydrobromic acid or 55% hydriodic acid afforded the corresponding halides, respectively. Silica gel could be recycled five times without any significant loss of activities.
- Tanemura, Kiyoshi
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supporting information
p. 4293 - 4298
(2018/11/10)
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- Site-Selective Aliphatic C-H Chlorination Using N-Chloroamides Enables a Synthesis of Chlorolissoclimide
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Methods for the practical, intermolecular functionalization of aliphatic C-H bonds remain a paramount goal of organic synthesis. Free radical alkane chlorination is an important industrial process for the production of small molecule chloroalkanes from simple hydrocarbons, yet applications to fine chemical synthesis are rare. Herein, we report a site-selective chlorination of aliphatic C-H bonds using readily available N-chloroamides and apply this transformation to a synthesis of chlorolissoclimide, a potently cytotoxic labdane diterpenoid. These reactions deliver alkyl chlorides in useful chemical yields with substrate as the limiting reagent. Notably, this approach tolerates substrate unsaturation that normally poses major challenges in chemoselective, aliphatic C-H functionalization. The sterically and electronically dictated site selectivities of the C-H chlorination are among the most selective alkane functionalizations known, providing a unique tool for chemical synthesis. The short synthesis of chlorolissoclimide features a high yielding, gram-scale radical C-H chlorination of sclareolide and a three-step/two-pot process for the introduction of the β-hydroxysuccinimide that is salient to all the lissoclimides and haterumaimides. Preliminary assays indicate that chlorolissoclimide and analogues are moderately active against aggressive melanoma and prostate cancer cell lines.
- Quinn, Ryan K.,K?nst, Zef A.,Michalak, Sharon E.,Schmidt, Yvonne,Szklarski, Anne R.,Flores, Alex R.,Nam, Sangkil,Horne, David A.,Vanderwal, Christopher D.,Alexanian, Erik J.
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p. 696 - 702
(2016/02/03)
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- Synthesizing method of pesticide intermediate 1-methylcyclohexanecarboxylic acid
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The invention discloses a synthesizing method of a pesticide intermediate 1-methylcyclohexanecarboxylic acid. The 1-methylcyclohexanecarboxylic acid is prepared by taking 2-methylcyclohexanol, formic acid and an R-Cl halogenating reagent as the raw materials through halogenation and substitution reactions by means of a one-pot method. The synthesizing method is novel, the defects in a traditional production process can be overcome, emission of waste acid water is reduced, the production capacity is enlarged, and the synthesizing method is green and environmentally friendly.
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Paragraph 0019; 0020
(2017/06/02)
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- Kinetics and mechanism of unimolecular heterolysis of cage-like compounds: XIX. Effect of the nucleofuge nature on the activation parameters of heterolysis of 1-halo-1-methylcyclohexanes in cyclohexane. Heterolysis rate ratio in aprotic and protic solvents
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Heterolysis of 1-bromo-1-methylcyclohexane in cyclohexane (E1 reaction) involves solvation of the transition state (ΔS≠ = -81 J mol-1K-1), while heterolysis of 1-chloro-1- methylcyclohexane is characterized by desolvation of the transition state (ΔS≠ = 92 J mol-1K-1). The probability for the formation of transition state (interaction between cationoid intermediate and solvent cavity) increases in the first case due to enhanced stability of the solvated intermediate, and in the second, due to reduction in its size. The bromide/chloride heterolysis rate ratio decreases as the ionizing power of aprotic solvent decreases and that of protic solvent increases.
- Dvorko,Koshchii,Ponomareva
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- A remarkably efficient Markovnikov hydrochlorination of olefins and transformation of nitriles into imidates by use of AcCl and an alcohol
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HCl generated by mixing AcCl with EtOH brings about Markovnikov hydrochlorination of olefins in excellent yields. The products are isolated in states of high purity simply by removal of the volatile components under reduced pressure. Further, nitriles are transformed into imidate hydrochlorides on similar treatment with AcCl and an alcohol. This procedure for nitrile-imidate transformation is much more efficient than that used previously, which involved continuous passing of HCl gas into the solution of a nitrile in a solvent such as Et2O or benzene and an alcohol until one equivalent had been absorbed. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005.
- Yadav, Veejendra K.,Babu, K. Ganesh
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p. 452 - 456
(2007/10/03)
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- Reactivity of bismuth(III) halides towards alcohols. A tentative to mechanistic investigation
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The reactivity of bismuth(III) halides (BiX3; X=Cl, Br and I) towards a series of alcohols has been investigated. Three different reactions have been studied, namely: halogenation, dehydration and etherification. The behaviour of these bismuth derivatives was found to depend on the nature of the halide bonded to the bismuth atom. Their reactivities can be interpreted on the basis of the Hard and Soft Acids and Bases (HSAB) principle. A mechanism is proposed which involves the formation of a complex of the alcohol with Bi(III).
- Keramane, El Mehdi,Boyer, Bernard,Roque, Jean-Pierre
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p. 1909 - 1916
(2007/10/03)
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- Formation of three-membered rings by SHi displacement. Reverse of cyclopropyl ring opening
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The general methods, photoinitiated or peroxide-initiated free radical chain additions of halomethanes to olefins, yield 1,2-addition products at temperatures ranging from 20 to 100°C. At lower temperatures, -42 to -104°C, a competitive reaction, subsequent to the addition of CCl2X., yields alkylcyclopropanes. The reactions of 1-octene or 1-hexene and 1-methylcyclohexene with atomic hydrogen carried out in the presence of several transfer agents (CCl4, CCl3Br, CCl2Br2) initiate a radical chain addition of CCl2X. and yield cyclized materials resulting from the SHi displacement of halogen by a carbon-centered radical. The radical displacement of a halogen on carbon, the reverse of homolytic displacement on cyclopropyl carbon, is dominant at low temperatures. The rate constants for cyclization (kc) vs transfer with halomethane (kt) showed isokinetic temperatures of -46°C (CCl4, 1-hexene); -35°C (CCl4, 1-methylcyclohexene). The isokinetic temperatures for the reactions of the two substrates carried out in the presence of BrCCl3 were calculated as -204 °C (1-octene) and -109°C (1-methylcyclohexene).
- Tanner, Dennis D.,Zhang, Liying,Hu, Li Qing,Kandanarachchi, Pramod
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p. 6818 - 6824
(2007/10/03)
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- The Reaction between Acyl Halides and Alcohols: Alkyl Halide vs. Ester Formation
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In the reaction between an acyl halide and an alcohol the thermodynamically favoured products are the free carboxylic acid and the alkyl halide.The initial reaction is, generally, the formation of an ester and HHal.When the alcohol is very prone to yield an alkyl cation upon protonation by HHal, formed H2O exhibited a superior reactivity and competed successfully with the alcohol for the acyl halide making, therefore, ester formation practically confined to a triggering role.But, in those cases where the cation is less easily formed, ester formation was favoured and, consequently, became the necessary elementary step towards alkyl halide formation.Tis final product, on the other hand, might be extremely slow to form in an SN2 reaction between the protonated ester function and the halide ion.In these instances, therefore, as well as in the cases when a basic solvent competes for the proton of HHal, the ester is the final product.A notable exception of the situation above outlined, is given by α-hydroxy-α-phenylbenzeneacetic acid (2y), which appears to undergo direct chlorine-hydroxyl interchange through a quaternary intermediate (E), in the end collapsing to α-chloro-α-phenyl-benzeneacetic acid (4y).Different systems were compared using CH2Cl2 as a solvent under strictly similar conditions.Some 28 different substrates were tested for reaction with AcCl (1a), whereas the action of eight acyl halides (a) against (RS)-α-methylbenzenemethanol (2n) and α-phenylbenzenemethanol (2p), as well as the effect of five different solvents on the reaction between two alcohols (2p and 2-methyl-2-propanol, 2c) with 1a, were observed.
- Strazzolini, Paolo,Giumanini, Angelo G.,Verardo, Giancarlo
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p. 217 - 254
(2007/10/02)
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- Surface-mediated reactions. 3. Hydrohalogenation of alkenes
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Appropriately prepared silica gel and alumina have been found to mediate the addition of HCl, HBr, and HI to alkenes. The technique has been rendered even more convenient by the use of various organic and inorganic halides that undergo hydrolysis in the presence of silica gel or alumina to generate hydrogen halides in situ. Under these conditions alkenes such as cycloheptene (1), 1-octene (7), and 3,3-dimethyl-1-butene (15), which react with HCl only very slowly in solution, underwent rapid addition. 1-Octene (7) underwent ionic addition of HBr without competing radical addition. 1,2-Dimethylcyclohexane (24) afforded the syn addition product 25c, which underwent equilibration with the thermodynamically more stable isomer 25t. A mechanism for surface-mediated addition/elimination is proposed involving a stepwise transfer of H+ and X- from or to the surface in syn fashion, as shown in Scheme II.
- Kropp, Paul J.,Daus, Kimberlee A.,Tubergen, Mark W.,Kepler, Keith D.,Wilson, Vincent P.,Craig, Stephen L.,Baillargeon, Michelle M.,Breton, Gary W.
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p. 3071 - 3079
(2007/10/02)
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- Regioselective Hydrochlorination of Olefins Is Favored by an Acidic Solid Catalyst
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With thionyl chloride SOCl2 as HCl precursor, 1-methylcyclohexene is hydrochlorinated.In the absence of a solid catalyst, between half and two-thirds of the product mixture are the anti-Markovnikov adduct, trans-1-chloro-2-methylcyclohexane.Catalysis by the ZF 520 zeolite or the K 10 montmorillonite makes the reaction selective.It then affords a quantitative yield of (10:1) Markovnikov adduct 1-chloro-1-methylcyclohexane. Key Words: Markovnikov; Anti-Markovnikov; Ionic; Radical; High Yield and Selectivity
- Delaude, Lionel,Laszlo, Pierre
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p. 3705 - 3708
(2007/10/02)
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- CHLORIERENDE METHYLIERUNG VON ALDEHYD- UND KETOGRUPPEN MIT NIOB-REAGENZIEN SOWIE AUFKLAERUNG DES MECHANISMUS
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The reagents MeNbCl4 and Me2NbCl3, applied as isolated pure compounds, react with ketones in preparatively useful yields according to RR'CO -> RR'C(Cl)CH3.Whereas benzaldehyde reacts with MeNbCl4 analogously, the aliphatic aldehyde heptanal forms beside the expected product two cinechlorination products, indicating a mechanism via radicals.MeNbCl4 is highly aldehyde-vs.-ketone selective.Conversely, high ketone-vs.-aldehyde selectivity is achievable by application of MeNbCl4*PPh3 or NbCl5*PPh3 + 1.5 Me2Zn.
- Kauffmann, Thomas,Abel, Thomas,Neiteler, Gabriele,Schreer, Martin
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p. 503 - 506
(2007/10/02)
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- The Interaction of Arenesulphonyl Chlorides, Aluminium Chloride, and Saturated Alicyclic Hydrocarbons containing at least One Tertiary Hydrogen Atom
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Cycloalkanes having at least one tertiary hydrogen react with a mixture of benzenesulphonyl chloride and aluminium chloride in carbon disulphide, with reactivity decreasing in the order cis-decalin ca. cis-hexahydroindane > trans-decalin >/= dicyclohexyl > methylcyclohexane > t-butylcyclohexane > methylcyclopentane.Although hydrogen chloride was evolved and benzenesulphonyl chloride was reduced to benzenesulphinic acid in all the reactions, only cis-decalin, and, to a much smaller extent, dicyclohexyl, gave appreciable amounts of chloro- or dichloro-cycloalkanes.In other reactions the major products were hydrocarbon "dimers" and "trimers" apparently formed by attack by the carbenium ion on cycloalkenes formed in the reaction.Electron-attracting substituents in the arenesulphonyl chloride enhanced the rate of reaction with cis-decalin, and electron-donor substituents retarded the reaction, which appears to proceed via hydride-ion abstraction by the arenesulphonyl halide-aluminium halide "oxonium complex" rather than by the (+) ion.
- Ewedemi, Rotimi O.,Fields, Roy,Holt, Geoffrey
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p. 1466 - 1500
(2007/10/02)
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- Direct Geminal Dimethylation of Ketones and Exhaustive Methylation of Carboxylic Acid Chlorides Using Dichlorodimethyltitanium
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The reaction of ketones with an excess of (CH3)2TiCl2 (6) leads to the replacement of the carbonyl oxygen atom by two methyl groups.This mild method of direct geminal dimethylation involves Grignard-type addition followed by formation of tertiary carbocations which are captured by methyltitanium species.Additional functional groups such as primary alkyl chlorides, thioethers, aromatics, ethers and esters are tolerated, but not thioketals.The procedure has been applied to the synthesis of (+/-)-cuparene (44).Similarly, carboxylic acid chlorides are converted to tert-butyl derivatives.
- Reetz, Manfred T.,Westermann, Juergen,Kyung, Suk-Hun
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p. 1050 - 1057
(2007/10/02)
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- Role of Hydroperoxides in the Ozonized Oxidation of Cycloalkanes
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Rate constants have been determined for the action of ozone on cyclohexyl and 1-methylcyclohexyl hydroperoxides, which are formed by the oxidation of of cyclohexane and methylcyclohexane respectively.The reactivity of peroxy-compounds towards ozone diminishes in the sequence-cyclohexylhydroperoxide (I) > peroxydicyclohexane-1,1'-diol (IV) > 1,1'-hydroperoxycyclohexylperoxycyclohexanol (III) > peroxy-1,1'-dicyclohexane dihydroperoxide (V) > 1-methylcyclohexylhydroperoxide (II).
- Vikhorev, A. A.,Syroezhko, A. M.,Proskuryakov, V. A.,Korotkova, N. P.
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p. 251 - 253
(2007/10/02)
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- Stabilities of Carbonium Ions in Solution. 12. Heats of Formation of Alkyl Chlorides as an Entree to Heats of Solvation of Aliphatic Carbonium Ions
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Heats of formation (ΔHf) of tertiary alkyl chlorides may be calculated from measurements of the heats of hydrochlorination of appropriate olefins at -50 deg C in CH2Cl2.Since many good values for heats of formation of the olefins have been published, the heats of hydrochlorination lead directly to ΔHf for the chlorides, for which few previous values are available.The new data, when combined with previously reported heats of ionization for the chlorides, provide heats of formation for the carbonium ions.Relative values for ΔHf for the carbonium ions are remarkably similar in the gas phase and in SO2ClF, thus supporting the proposal that differential solvation of carbonium ions is small in solvents such as SO2ClF.Because solvation energies are nearly constant for carbonium ions, their relative energies as calculated from quantum theory should apply directly to nonnucleophilic condensed phase values - a situation which is drastically different from that for ammonium or oxonium ions.We have shown previously the close relationship between ionization energies for alkyl chlorides in SO2ClF and their solvolysis rates in ethanol.The present results complete the series of data which are necessary for rigorously relating theoretical calculations of carbonium ion stability to solvolysis reaction rates in solution.Thereby, they help to explain the great success of the carbonium ion theory of organic chemistry.
- Arnett, Edward M.,Pienta, Norbert J.
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p. 3329 - 3334
(2007/10/02)
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