- Non-Heme-Iron-Mediated Selective Halogenation of Unactivated Carbon?Hydrogen Bonds
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Oxidation of the iron(II) precursor [(L1)FeIICl2], where L1 is a tetradentate bispidine, with soluble iodosylbenzene (sPhIO) leads to the extremely reactive ferryl oxidant [(L1)(Cl)FeIV=O]+ with a cis disposition of the chlorido and oxido coligands, as observed in non-heme halogenase enzymes. Experimental data indicate that, with cyclohexane as substrate, there is selective formation of chlorocyclohexane, the halogenation being initiated by C?H abstraction and the result of a rebound of the ensuing radical to an iron-bound Cl?. The time-resolved formation of the halogenation product indicates that this primarily results from sPhIO oxidation of an initially formed oxido-bridged diiron(III) resting state. The high yield of up to >70 % (stoichiometric reaction) as well as the differing reactivities of free Fe2+ and Fe3+ in comparison with [(L1)FeIICl2] indicate a high complex stability of the bispidine-iron complexes. DFT analysis shows that, due to a large driving force and small triplet-quintet gap, [(L1)(Cl)FeIV=O]+ is the most reactive small-molecule halogenase model, that the FeIII/radical rebound intermediate has a relatively long lifetime (as supported by experimentally observed cage escape), and that this intermediate has, as observed experimentally, a lower energy barrier to the halogenation than the hydroxylation product; this is shown to primarily be due to steric effects.
- Bleher, Katharina,Comba, Peter,Faltermeier, Dieter,Gupta, Ashutosh,Kerscher, Marion,Krieg, Saskia,Martin, Bodo,Velmurugan, Gunasekaran,Yang, Shuyi
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supporting information
(2021/12/09)
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- Mechanism of Ni-catalyzed oxidations of unactivated C(sp3)-H Bonds
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The Ni-catalyzed oxidation of unactivated alkanes, including the oxidation of polyethylenes, by meta-chloroperbenzoic acid (mCPBA) occur with high turnover numbers under mild conditions, but the mechanism of such transformations has been a subject of debate. Putative, high-valent nickel-oxo or nickel-oxyl intermediates have been proposed to cleave the C-H bond, but several studies on such complexes have not provided strong evidence to support such reactivity toward unactivated C(sp3)-H bonds. We report mechanistic investigations of Ni-catalyzed oxidations of unactivated C-H bonds by mCPBA. The lack of an effect of ligands, the formation of carbon-centered radicals with long lifetimes, and the decomposition of mCPBA in the presence of Ni complexes suggest that the reaction occurs through free alkyl radicals. Selectivity on model substrates and deuterium-labeling experiments imply that the m-chlorobenzoyloxy radical derived from mCPBA cleaves C-H bonds in the alkane to form an alkyl radical, which subsequently reacts with mCPBA to afford the alcohol product and regenerate the aroyloxy radical. This free-radical chain mechanism shows that Ni does not cleave the C(sp3)-H bonds as previously proposed; rather, it catalyzes the decomposition of mCPBA to form the aroyloxy radical.
- Qiu, Yehao,Hartwig, John F.
-
supporting information
p. 19239 - 19248
(2020/11/13)
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- Thiourea-Mediated Halogenation of Alcohols
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The halogenation of alcohols under mild conditions expedited by the presence of substoichiometric amounts of thiourea additives is presented. The amount of thiourea added dictates the pathway of the reaction, which may diverge from the desired halogenation reaction toward oxidation of the alcohol, in the absence of thiourea, or toward starting material recovery when excess thiourea is used. Both bromination and chlorination were highly efficient for primary, secondary, tertiary, and benzyl alcohols and tolerate a broad range of functional groups. Detailed electron paramagnetic resonance (EPR) studies, isotopic labeling, and other control experiments suggest a radical-based mechanism. The fact that the reaction is carried out at ambient conditions, uses ubiquitous and inexpensive reagents, boasts a wide scope, and can be made highly atom economic, makes this new methodology a very appealing option for this archetypical organic reaction.
- Mohite, Amar R.,Phatake, Ravindra S.,Dubey, Pooja,Agbaria, Mohamed,Shames, Alexander I.,Lemcoff, N. Gabriel,Reany, Ofer
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supporting information
p. 12901 - 12911
(2020/11/26)
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- N -Hydroxyphthalimide/benzoquinone-catalyzed chlorination of hydrocarbon C-H bond using N -chlorosuccinimide
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The direct chlorination of C-H bonds has received considerable attention in recent years. In this work, a metal-free protocol for hydrocarbon C-H bond chlorination with commercially available N-chlorosuccinimide (NCS) catalyzed by N-hydroxyphthalimide (NHPI) with 2,3-dicyano-5,6-dichlorobenzoquinone (DDQ) functioning as an external radical initiator is presented. Aliphatic and benzylic substituents and also heteroaromatic ones were found to be well tolerated. Both the experiments and theoretical analysis indicate that the reaction goes through a process wherein NHPI functions as a catalyst rather than as an initiator. On the other hand, the hydrogen abstraction of the C-H bond conducted by a PINO species rather than the highly reactive N-centered radicals rationalizes the high chemoselectivity of the monochlorination obtained by this protocol as the latter is reactive towards the C(sp3)-H bonds of the monochlorides. The present results could hold promise for further development of a nitroxy-radical system for the highly selective functionalization of the aliphatic and benzylic hydrocarbon C-H.
- Li, Zi-Hao,Fiser, Béla,Jiang, Biao-Lin,Li, Jian-Wei,Xu, Bao-Hua,Zhang, Suo-Jiang
-
supporting information
p. 3403 - 3408
(2019/04/01)
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- Mechanism of Hydrocarbon Functionalization by an Iodate/Chloride System: The Role of Ester Protection
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Mixtures of chloride and iodate salts for light alkane oxidation achieve >20% yield of methyl trifluoroacetate (TFA) from methane with >85% selectivity. The mechanism of this C-H oxygenation has been probed by examining adamantane as a model substrate. These recent results lend support to the involvement of free radicals. Comparative studies between radical chlorination and iodate/chloride functionalization of adamantane afford statistically identical 3°:2° selectivities (~5.2:1) and kinetic isotope effects for C-H/C-D functionalization (kH/kD = 1.6(3), 1.52(3)). Alkane functionalization by iodate/chloride in HTFA is proposed to occur through H-atom abstraction by free radical species including Cl? to give alkyl radicals. Iodine, which forms by in situ reduction of iodate, traps alkyl radicals as alkyl iodides that are subsequently converted to alkyl esters in HTFA solvent. Importantly, the alkyl ester products (RTFA) are quite stable to further oxidation under the oxidizing conditions due to the protecting nature of the ester moiety.
- Schwartz, Nichole A.,Boaz, Nicholas C.,Kalman, Steven E.,Zhuang, Thompson,Goldberg, Jonathan M.,Fu, Ross,Nielsen, Robert J.,Goddard, William A.,Groves, John T.,Gunnoe, T. Brent
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p. 3138 - 3149
(2018/04/14)
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- KOtBu as a single electron donor? Revisiting the halogenation of alkanes with CBr4 and CCl4
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The search for reactions where KOtBu and other tert-alkoxides might behave as single electron donors led us to explore their reactions with tetrahalomethanes, CX4, in the presence of adamantane. We recently reported the halogenation of adamantane under these conditions. These reactions appeared to mirror the analogous known reaction of NaOH with CBr4 under phase-transfer conditions, where initiation features single electron transfer from a hydroxide ion to CBr4. We now report evidence from experimental and computational studies that KOtBu and other alkoxide reagents do not go through an analogous electron transfer. Rather, the alkoxides form hypohalites upon reacting with CBr4 or CCl4, and homolytic decomposition of appropriate hypohalites initiates the halogenation of adamantane.
- Emery, Katie J.,Young, Allan,Arokianathar, J. Norman,Tuttle, Tell,Murphy, John A.
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supporting information
(2018/05/22)
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- Highly selective halogenation of unactivated C(sp3)-H with NaX under co-catalysis of visible light and Ag@AgX
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The direct selective halogenation of unactivated C(sp3)-H bonds into C-halogen bonds was achieved using a nano Ag/AgCl catalyst at RT under visible light or LED irradiation in the presence of an aqueous solution of NaX/HX as a halide source, in air. The halogenation of hydrocarbons provided mono-halide substituted products with 95% selectivity and yields higher than 90%, with the chlorination of toluene being 81%, far higher than the 40% conversion using dichlorine. Mechanistic studies demonstrated that the reaction is a free radical process using blue light (450-500 nm), with visible light being the most effective light source. Irradiation is proposed to cause AgCl bonding electrons to become excited and electron transfer from chloride ions induces chlorine radical formation which drives the substitution reaction. The reaction provides a potentially valuable method for the direct chlorination of saturated hydrocarbons.
- Liu, Shouxin,Zhang, Qi,Tian, Xia,Fan, Shiming,Huang, Jing,Whiting, Andrew
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p. 4729 - 4737
(2018/10/23)
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- Experimental and theoretical studies of a greener catalytic system for saturated hydrocarbon chlorination composed by trichloroisocyanuric acid and a copper(II) compound
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We are describing herein a new environmentally friendly catalytic system able to convert cyclohexane to chlorocyclohexane with 100% selectivity. The method was also applied to the chlorination of n-hexane and adamantane. The catalytic system employs thichloroisocyanuric acid (TCCA) as halogenating agent and a mononuclear copper(II) complex [Cu(BPAH)(H2O)](ClO4)2, 1, as catalyst (BPAH = 1,4-bis(propanamide)homopiperazine), whose molecular structure was solved by monocrystal X-ray diffraction. For cyclohexane, at a ratio catalyst:substrate:TCCA of 1:1000:333, the system reached a conversion of 32.0 ± 1% at 25 °C and 44.7 ± 0.4% at 50 °C, with 100% selectivity for chlorocyclohexane. With n-hexane, a similar conversion was observed at 50 °C, resulting in mixture of monochlorides. Employing adamantane as substrate, the isomers 1-chloroadamantane and 2-chloroadamante were preferentially formed, together with traces of dichloroadamantane. EPR and ESI-(+)-MS analyses indicate the formation of a Cu-hypochlorite intermediate species, which is supported by theoretical calculations.
- Melo, Isis L.,Lube, Leonardo M.,Neves, Eduardo S.,Terra, Wagner S.,Fernandes, Christiane,Matos, Carlos R.R.,Franco, Roberto W.A.,Resende, Jackson A.L.C.,Valente, Daniel C.A.,Horta, Bruno A.C.,Cardozo, Thiago M.,Horn, Adolfo
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p. 150 - 158
(2018/06/14)
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- Mild Aliphatic and Benzylic Hydrocarbon C-H Bond Chlorination Using Trichloroisocyanuric Acid
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We present the controlled monochlorination of aliphatic and benzylic hydrocarbons with only 1 equiv of substrate at 25-30 °C using N-hydroxyphthalimide (NHPI) as radical initiator and commercially available trichloroisocyanuric acid (TCCA) as the chlorine source. Catalytic amounts of CBr4 reduced the reaction times considerably due to the formation of chain-carrying ·CBr3 radicals. Benzylic C-H chlorination affords moderate to good yields for arenes carrying electron-withdrawing (50-85%) or weakly electron-donating groups (31-73%); cyclic aliphatic substrates provide low yields (24-38%). The products could be synthesized on a gram scale followed by simple purification via distillation. We report the first direct side-chain chlorination of 3-methylbenzoate affording methyl 3-(chloromethyl)benzoate, which is an important building block for the synthesis of vasodilator taprostene.
- Combe, Sascha H.,Hosseini, Abolfazl,Parra, Alejandro,Schreiner, Peter R.
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p. 2407 - 2413
(2017/03/11)
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- Visible Light-Induced Oxidative Chlorination of Alkyl sp3 C-H Bonds with NaCl/Oxone at Room Temperature
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A visible light-induced monochlorination of cyclohexane with sodium chloride (5:1) has been successfully accomplished to afford chlorocyclohexane in excellent yield by using Oxone as the oxidant in H2O/CF3CH2OH at room temperature. Other secondary and primary alkyl sp3 C-H bonds of cycloalkanes and functional branch/linear alkanes can also be chlorinated, respectively, under similar conditions. The selection of a suitable organic solvent is crucial in these efficient radical chlorinations of alkanes in two-phase solutions. It is studied further by the achievement of high chemoselectivity in the chlorination of the benzyl sp3 C-H bond or the aryl sp2 C-H bond of toluene.
- Zhao, Mengdi,Lu, Wenjun
-
supporting information
p. 4560 - 4563
(2017/09/11)
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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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supporting information
p. 696 - 702
(2016/02/03)
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- 2-Substituted and 2,2-disubstituted adamantane derivatives as models for studying substituent chemical shifts and C-Hax?Yax cyclohexane contacts - results from experimental and theoretical NMR spectroscopic chemical shifts and DFT structures
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Abstract The complete 1H and 13C NMR chemical shifts assignment for various 2-substituted and 2,2-disubstituted adamantane derivatives 1-38 in CDCl3 solution was realized on the basis of NMR experiments combined with chemical structure information and DFT-GIAO (B3LYP/6-31+G(d,p)-GIAO) calculations of chemical shifts in solution. Substituent-induced 13C NMR chemical shifts (SCS) are discussed. C-Hax?Yax contacts are a textbook prototype of steric hindrance in organic chemistry. The nature of these contacts will be further investigated in this work on basis of new adamantane derivatives, which are substituted at C-2 to provide models for 1,4-C-Hax?Yax and 1,5-C-Hax?Yax contacts. The B3LYP/6-31+G(d,p) calculations predicted the presence of NBO hyperconjugative attractive interactions between C-Hax and Yax groups along C-Hax?Yax contacts. The 1H NMR signal separation, Δδ(γ-CH2), reflects the strength of the H-bonded C-Haxa?Yax contact.
- Kolocouris, Antonios,Koch, Andreas,Kleinpeter, Erich,Stylianakis, Ioannis
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p. 2463 - 2481
(2015/03/30)
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- Spectroscopic Analyses on Reaction Intermediates Formed during Chlorination of Alkanes with NaOCl Catalyzed by a Nickel Complex
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The spectroscopic, electrochemical, and crystallographic characterization of [(Me,HPyTACN)NiII(CH3CN)2](OTf)2 (1) (Me,HPyTACN = 1-(2-pyridylmethyl)-4,7-dimethyl-1,4,7-triazacyclononane, OTf = CF3SO3) is described together with its reactivity with NaOCl. 1 catalyzes the chlorination of alkanes with NaOCl, producing only a trace amount of oxygenated byproducts. The reaction was monitored spectroscopically and by high resolution electrospray-mass spectrometry (ESI-MS) with the aim to elucidate mechanistic aspects. NaOCl reacts with 1 in acetonitrile to form the transient species [(L)NiII-OCl(S)]+ (A) (L = Me,HPyTACN, S = solvent), which was identified by ESI-MS. UV/vis absorption, electron paramagnetic resonance, and resonance Raman spectroscopy indicate that intermediate A decays to the complex [(L)NiIII-OH(S)]2+ (B) presumably through homolytic cleavage of the O-Cl bond, which liberates a Cl? atom. Hydrolysis of acetonitrile to acetic acid under the applied conditions results in the formation of [(L)NiIII-OOCCH3(S)]2+ (C), which undergoes subsequent reduction to [(L)NiII-OOCCH3(S)]2+ (D), presumably via reaction with OCl- or ClO2-. Subsequent addition of NaOCl to [(L)NiII-OOCCH3(S)]+ (D) regenerates [(L)NiIII-OH(S)]2+ (B) to a much greater extent and at a faster rate. Addition of acids such as acetic and triflic acid enhances the rate and extent of formation of [(L)NiIII-OH(S)]2+ (B) from 1, suggesting that O-Cl homolytic cleavage is accelerated by protonation. Overall, these reactions generate Cl? atoms and ClO2 in a catalytic cycle where the nickel center alternates between Ni(II) and Ni(III). Chlorine atoms in turn react with the C-H bonds of alkanes, forming alkyl radicals that are trapped by Cl? to form alkyl chlorides.
- Draksharapu, Apparao,Codolà, Zoel,Gómez, Laura,Lloret-Fillol, Julio,Browne, Wesley R.,Costas, Miquel
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p. 10656 - 10666
(2015/11/27)
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- Stereoretentive chlorination of cyclic alcohols catalyzed by titanium(IV) tetrachloride: Evidence for a front side attack mechanism
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A mild chlorination reaction of alcohols was developed using the classical thionyl chloride reagent but with added catalytic titanium(IV) chloride. These reactions proceeded rapidly to afford chlorination products in excellent yields and with preference for retention of configuration. Stereoselectivities were high for a variety of chiral cyclic secondary substrates including sterically hindered systems. Chlorosulfites were first generated in situ and converted to alkyl chlorides by the action of titanium tetrachloride which is thought to chelate the chlorosulfite leaving group and deliver the halogen nucleophile from the front face. To better understand this novel reaction pathway, an ab initio study was undertaken at the DFT level of theory using two different computational approaches. This computational evidence suggests that while the reaction proceeds through a carbocation intermediate, this charged species likely retains pyramidal geometry existing as a conformational isomer stabilized through hyperconjugation (hyperconjomers). These carbocations are then essentially "frozen" in their original configurations at the time of nucleophilic capture.
- Mondal, Deboprosad,Li, Song Ye,Bellucci, Luca,Laino, Teodoro,Tafi, Andrea,Guccione, Salvatore,Lepore, Salvatore D.
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p. 2118 - 2127
(2013/04/10)
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- A facile and green protocol for nucleophilic substitution reactions of sulfonate esters by recyclable ionic liquids [bmim][X]
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Ionic liquids [bmim][X] (X = Cl, Br, I, OAc, SCN) are highly efficient reagents for nucleophilic substitution reactions of sulfonate esters derived from primary and secondary alcohols. The counter anions (X-) of the ionic liquids, [bmim][X], effectively replace the sufonates affording the corresponding substitution products such as alkyl halides, acetates, and thiocyanides in excellent yields. The newly developed protocol is very environmentally attractive because the reactions use stoichiometric amounts of ionic liquids as sole reagents in most cases and do not require additional solvents, any other activating reagents, non-conventional equipment, or special precautions. Moreover, these ionic liquids can be readily recycled without loss of reactivity, making the whole process greener.
- Liu, Yajun,Xu, Yongnan,Jung, Sun Ho,Chae, Junghyun
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p. 2692 - 2698,7
(2012/12/12)
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- A facile and green protocol for nucleophilic substitution reactions of sulfonate esters by recyclable ionic liquids [bmim][X]
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Ionic liquids [bmim][X] (X = Cl, Br, I, OAc, SCN) are highly efficient reagents for nucleophilic substitution reactions of sulfonate esters derived from primary and secondary alcohols. The counter anions (X-) of the ionic liquids, [bmim][X], effectively replace the sufonates affording the corresponding substitution products such as alkyl halides, acetates, and thiocyanides in excellent yields. The newly developed protocol is very environmentally attractive because the reactions use stoichiometric amounts of ionic liquids as sole reagents in most cases and do not require additional solvents, any other activating reagents, non-conventional equipment, or special precautions. Moreover, these ionic liquids can be readily recycled without loss of reactivity, making the whole process greener. Georg Thieme Verlag KG Stuttgart · New York.
- Liu, Yajun,Xu, Yongnan,Jung, Sun Ho,Chae, Junghyun
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p. 2692 - 2698
(2013/01/15)
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- Iron(III)-catalyzed halogenations by substitution of sulfonate esters
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A novel halogenation reaction from sulfonates catalyzed by iron(III) is described. The reaction can be performed as a stoichiometric or a catalytic version. This reaction provides a convenient strategy for the efficient access to structurally diverse secondary chlorides, bromides and iodides. The stereochemical course of the reaction is governed by the substrate and the experimental conditions. Secondary alcohols modified as quisylates or pysylates are substantially more reactive. Aliphatic quisylates proceed with overall inversion of configuration under catalytic conditions. Chemoselectivity in bismesylates was observed in favour of the secondary mesylate. Additionally, based on the experimental results, a possible catalytic cycle for the halogenation has been proposed.
- Ortega, Nuria,Feher-Voelger, Andres,Brovetto, Margarita,Padron, Juan I.,Martin, Victor S.,Martin, Tomas
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p. 963 - 972
(2011/06/20)
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- Oxidation of alkane using Pt/Eu2O3/TiO 2/SiO2 catalyst with O2 and H2 in acetic acid under mild conditions
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A new solid catalyst of Pt/Eu2O3/TiO 2/SiO2 for oxidation of alkane was developed. Oxidation of adamantane using the multi-components supported catalyst with O2 and H2 was studied in acetic acid at 313 K. Several multi-components supported catalysts were prepared and tested the oxidation activity. It is found that loading order of Eu2O3, TiO2 and Pt on the SiO2 support strongly affected the oxidation catalysis. The active catalysts model was proposed from TEM-EDS analysis that very small Pt particles well dispersed on amorphous Eu2O3 and TiO 2 on the SiO2 support. Eu and Ti oxides concertedly activated O2 with electrons supplied from H2 on Pt, and active oxygen species efficiently oxidized adamantane and other alkanes to oxygenated compounds. Active oxygen species could not be identified but its reactivity was studied. It showed radical nature for oxidation of alkanes and a cleavage of C-H bond was the rate-determining step during the oxidation.
- Yamanaka, Ichiro,Suzuki, Yuta,Toida, Masashi
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experimental part
p. 286 - 290
(2011/01/04)
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- Chlorination of various substrates in subcritical carbon tetrachloride
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Various aliphatic hydrocarbons and the side chains of aromatic hydrocarbons were chlorinated in subcritical carbon tetrachloride. Chlorination of aromatic compounds including 1,4-disubstituted benzenes was investigated. Ketones and sulfones were stable under the employed conditions. Sulfoxides were converted into sulfides in a low to modest yields. The coupling adducts between olefins and carbon tetrachloride were obtained from the reactions of olefins.
- Tanemura, Kiyoshi,Suzuki, Tsuneo,Nishida, Yoko,Horaguchi, Takaaki
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scheme or table
p. 2881 - 2888
(2010/06/16)
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- The halogenation of aliphatic C-H bonds with peracetic acid and halide salts
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Hydrocarbons react with molar concentrations of peracetic acid and halide salts to yield predominantly monohalogenated products under optimum conditions, with chlorination being more oxidatively efficient than bromination. The alkane halogenation proceeds at ambient temperature and does not require a heavy-metal catalyst. The observed reactivity is consistent with a radical mechanism, in which the peracid initially reacts with the halide ions to yield halogen-atom radicals, which ultimately oxidize the hydrocarbon. Although the reactivity proceeds slightly more efficiently in acetonitrile, the halogenation protocol works well in water.
- He, Yu,Goldsmith, Christian R.
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supporting information; experimental part
p. 1377 - 1380
(2010/08/06)
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- Direct chlorination of alcohols with chlorodimethylsilane catalyzed by a gallium trichloride/tartrate system under neutral conditions
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The reaction of secondary alcohols 1 with chlorodimethylsilane (HSiMe 2Cl) proceeded in the presence of a catalytic amount of GaCl 3/diethyl tartrate to give the corresponding organic chlorides 3. In the catalytic cycle, the reaction of diethyl tartrate 4a with HSiMe 2Cl 2 gives the chlorosilyl ether 5 with generation of H2. Alcohol-exchange between the formed chlorosilyl ether 5 and the substrate alcohol 1 affords alkoxychlorosilane 6, which reacts with catalytic GaCl 3 to give the chlorinated product 3. The moderate Lewis acidity of GaCl3 facilitates chlorination. Strong Lewis acids did not give product due to excessive affinity for the oxy-functionalities. Although tertiary alcohols were chlorinated by this system even in the absence of diethyl tartrate, certain alcohols that are less likely to give carbocationic species were effectively chlorinated using the GaCl3/diethyl tartrate system. The Royal Society of Chemistry.
- Yasuda, Makoto,Shimizu, Kenji,Yamasaki, Satoshi,Baba, Akio
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supporting information; experimental part
p. 2790 - 2795
(2009/02/03)
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- Chlorination of aliphatic hydrocarbons, aromatic compounds, and olefins in subcritical carbon tetrachloride
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The reactions of various substrates including aliphatic hydrocarbons, aromatic compounds, and olefins were investigated in subcritical carbon tetrachloride. Ketones and sulfones were stable under the employed conditions. The coupling adducts between olefins and carbon tetrachloride were obtained from the reactions of olefins.
- Tanemura, Kiyoshi,Suzuki, Tsuneo,Nishida, Yoko,Horaguchi, Takaaki
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scheme or table
p. 6419 - 6422
(2009/04/06)
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- An efficient method for chlorination of alcohols using PPh3/Cl3CCONH2
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A new and convenient method for the chlorination of alcohols utilizing PPh3/Cl3CCONH2 is addressed. Various alcohols could smoothly be converted into their corresponding alkyl chlorides in high yield under mild conditions with short reaction times. A mechanism is disclosed with the evidence of inversion of configuration of the analogous alkyl chloride derived from R-(-)-2-octanol.
- Pluempanupat, Wanchai,Chavasiri, Warinthorn
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p. 6821 - 6823
(2007/10/03)
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- Indium-catalyzed direct chlorination of alcohols using chlorodimethylsilane-benzil as a selective and mild system
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The InCl3-catalyzed reaction of alcohols with chlorodimethylsilane (HSiMe2Cl) in the presence of benzil gave the corresponding organic chlorides under mild conditions. Benzil significantly changes the reaction course because the reducing product through dehydroxyhydration was obtained in the absence of benzil. The secondary or tertiary alcohols were effectively chlorinated. The substrates bearing acid-sensitive functional groups were also applied to this system. The highly selective chlorination of the tertiary site was observed in the competitive reaction between tertiary and primary alcohols. The highly coordinated hydrosilane generated from benzil and HSiMe2Cl is an important intermediate. Copyright
- Yasuda, Makoto,Yamasaki, Satoshi,Onishi, Yoshiyuki,Baba, Akio
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p. 7186 - 7187
(2007/10/03)
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- Nucleophilic substitution induced by electron transfer at the bridgehead of polycyclic alkanes: Competition between polar and radical pathways
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A series of 2,5(or 1,4)-dihaloadamantanes (4 and 5, X = Y = halogens) and 9,10-dihalotriptycenes (7, X = Y = halogens) as well as two 5-halo (X) adamantan-2-ones (6, Y = O,X = Br and I) have been treated with Me3SnLi in THF in the absence and presence of tert-butylamine (TBA) and dicyclohexylphosphine (DCHP). The product distributions of these reactions have been established by 13C and 119Sn NMR spectroscopy, vapor-phase chromatographic analyses, and GC/MS. The former compounds (4 and 5) appear to react exclusively by a free-radical chain process (SRN1 mechanism) to yield tin substitution products. By contrast, the triptycenes react predominantly by a polar mechanism initiated by the formation of a carbanion. In the case of the halo ketones (6, Y = O,X = Br and I), a mechanistic divergence of the reaction was unexpectedly encountered. Whereas the bromo ketone provides the substitution product (6, Y = O,X = SnMe3) in good yield (ca. 75%), apparently by a radical pathway, the iodo ketone yields a fragmentation product (ca. 95% yield) by a polar mechanism. This mechanistic switch highlights the importance of the electronegativity of the leaving group as well as substituent-induced electron delocalization as molecular factors governing the competition between radical and polar pathways.
- Adcock,Clark,Trout
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p. 3362 - 3371
(2007/10/03)
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- A novel and highly effective halogenation of alkanes with halides on oxidation with m-Chloroperbenzoic acid: Looks old, but new reaction
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The combination of tetraalkylammonium halides (Cl-. Br-) and m-chloroperbenzoic acid in CH3CN effectively halogenated alkanes accompanied by the formation of alkyl m-chlorobenzoate; for which the alkyl halides were formed via a non-photoinduced radical mechanism and the esters were derived from a non-radical process and concomitant with the formation of corresponding trialkylamine.
- Kojima, Takahiko,Matsuo, Hidenobu,Matsuda, Yoshihisa
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p. 1085 - 1086
(2007/10/03)
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- Preparative catalytic chlorination of adamantane, cyclohexane, and hexane in the system tetrachloromethane-MX2(PPh3)2 (MX2 = PdBr2, PtCl2)-acetonitrile-potassium carbonate
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Heating of saturated hydrocarbons RH (cyclohexane, adamantane, and hexane) with tetrachloromethane in the presence of acetonitrile, potassium carbonate, and catalytic amounts of dihalide triphenylphosphine complexes of palladium(II) or platinum(II), MX2(PPh)2 (MX2 = PdBr2, PtCi2), for 6-8 h at 120°C yields monochlorinated derivatives of the respective hydrocarbons in 30-55% yield. Benzene, toluene, ethylbenzene, and tetramethylsilane show low reactivity under the conditions adopted for the reaction. Relative reactivity of various bond types C-H of alkanes is in agreement with the well known sequence: tertiary > secondary > primary. A scheme is proposed assuming trichloromethyl radicals as active species, and the catalyst function consists in activating C-C1 bond of the tetrachloromethane.
- Vedernikov,Sayakhov,Zazybin,Solomonov
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p. 812 - 815
(2007/10/03)
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- Enhanced nucleophilic character of the 1-adamantyl radical in chlorine atom abstraction and in addition to electron-poor alkenes and to protonated heteroaromatic bases. Absolute rate constants and relationship with the Gif reaction
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The absolute rate constants for reactions of the 1-adamantyl radical with electron-deficient substrates have been measured by competition kinetics. Addition to electron-poor alkenes or to protonated heteroaromatic bases, as well as chlorine abstraction from CCl4 and CHCl3, are two to three orders of magnitude faster than the corresponding reactions of the tert-butyl radical. This behaviour is ascribed to the enhanced nucleophilic character of the 1-adamantyl radical compared to generic tertiary alkyl radicals; it is related to the particular stability of the 1-adamantyl cation and to the low oxidation potential of adamantane. These results contribute to the understanding of the Gif reaction mechanism; in this debate, adamantane oxidation was one of the most controversial aspects because the 1-adamantyl radical is trapped by pyridinium ions, while the 2-adamantyl radical is not. This behaviour is explained by the large difference in the reactivity of the two isomeric adamantyl radicals towards protonated pyridine.
- Recupero, Francesco,Bravo, Anna,Bjorsvik, Hans-Rene,Fontana, Francesca,Minisci, Francesco,Piredda, Mariella
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p. 2399 - 2405
(2007/10/03)
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- On the triggering of free radical reactivity of dimethyldioxirane
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Performing the reaction in the presence of CCl3Br, and/or in inert gas atmosphere, dramatically changes the reation kinetics, rate-law and product distribution of adamantane oxyfunctionalization by dimethyldioxirane (1a). The kinetics of decomposition of the dioxirane is also markedly influenced by the addition of CCl3Br and by depletion of O2 gas. The data suggest that these conditions can trigger dioxirane radical reactions; these are widely different from the straightforward, highly selective concerted O-insertion into C-H bonds which would take place in the absence of CCl3Br and of conditions inducing radical reactivity.
- Curci, Ruggero,Dinoi, Anna,Fusco, Caterina,Lillo, Maria A.
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p. 249 - 252
(2007/10/02)
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- The functionalization of saturated hydrocarbons. Part 25. Ionic substitution reactions in GoAggIV chemistry: The formation of carbon-halogen bonds
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GoAggIV chemistry (Fe (III) species, tert-butyl hydroperoxide in a mixture of pyridine and acetic acid) in the presence of LiCl can transform saturated hydrocarbons efficiently into the corresponding alkyl chlorides. The transformation into monosubstituted alkyl derivatives by "ionic trapping" reagents arising from the interception of the first intermediate of the system supports the presence of a high valent VFe-C species. Mechanistic studies suggest a possible pathway operating via an Fe-centered ligand coupling. In addition, the production of alkyl chlorides and alkyl bromides could also be achieved employing this system in the presence of halogenating reagents such as CCl4 and BrCCl3.
- Barton, Derek H. R.,Beviere, Stephane D.,Chavasiri, Warinthorn
-
-
- The Fe(II)-Fe(IV) and Fe(III)-Fe(V) manifolds in an expanded world of gif chemistry
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The species responsible for hydrocarbon activation and formation of alkyl chlorides in the Fe(II) and Fe(III)-H2O2 and tert-butyl hydroperoxide systems are identified. The importance of the Fe(II)-Fe(IV) manifold in providing a mechanism which permits the selective functionalization of saturated hydrocarbons by ionic trapping with chloride, azide, and other anions is made manifest. Comparison is made with the Fe(III)-Fe(V) manifold where ionic trapping is never seen.
- Bardin,Barton,Hu,Rojas-Wahl,Taylor
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p. 5805 - 5808
(2007/10/02)
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- The Nature of Electronic Interactions Governing the Control of Π-Facial Selectivity in the Capture of 5-Substituted(X)-2-Adamantyl Radicals: Electrostatic versus Hyperconjugative Effects
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An electrostatic rather than a hyperconjugative effect appears to be the dominant factor governing the control of Π-facial selectivity in the capture of 5-substituted(X)-2-adamantyl radicals.
- Adcock, William,Clark, Christopher I.,Trout, Neil A.
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p. 297 - 300
(2007/10/02)
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- Regio- and chemo-selectivity of adamantane halogenation by Gif-Barton and metalloporphyrin catalysis and by classical free-radical reactions
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The halogenation of adamantane by CBrCl3 with Gif-Barton and metalloporphyrin catalysis is compared with classical free-radical halogenations (Br2, NBS, t-Bu-OCl, R2NCl) and with the behaviour of simple alkanes (n-hexane, 2,3-dimethylbutane, cyclohexane); the free-radical mechanism is discussed.
- Minisci,Minisci, Francesco,Fontana,Fontana, Francesca,Zhao,Zhao, Lihua,Banfi,Banfi, Stefane,Quici,Quici, Silvio
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p. 8033 - 8036
(2007/10/02)
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- The Effect of Triphenylphosphine in the GoAgg(II) System.
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The usual formation of ketone and alcohol under GoAgg(II) conditions can be totally replaced by the formation of the corresponding mono-alkyl substituted derivatives by addition of PPh3 and alkali metal salts.
- Barton, Derek H. R.,Beviere, Stephane D.
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p. 5689 - 5692
(2007/10/02)
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- Covenient Halodeamination and Hydrodeamination of Primary Amines
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Treatment of p-toluenesulfonamides of primary amines with 2 equiv of chloroamine at room temperature in the presence of base leads to reductive deamination.If excess chloroamine is present, the corresponding alkyl or aryl halides are obtained instead in good yields.Both reactions presumably proceed via tosylhydrazine and diazene intermediates; the course of the reaction is often governed by steric hindrance.Treatment of the isolated tosylhydrazine intermediate with base and chloroamine, bromine, or iodine also leads to the corresponding halides in very good yields.
- Guziec, Frank S.,Wei, Dongchu
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p. 3772 - 3776
(2007/10/02)
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- NICKEL(SALEN) CATALYSED CHLORINATION OF SATURATED HYDROCARBONS BY SODIUM HYPOCHLORITE
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In the presence of nickel(salen) as the catalyst, basic (pH 11) aqueous solutions of sodium hypochlorite chlorinate saturated hydrocarbons under very mild conditions.
- Querci, Cecilia,Strogolo, Sauro,Ricci, Marco
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p. 6577 - 6580
(2007/10/02)
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- IMPROVED SYNTHESIS OF 1-CHLOROADAMANTANE BY HYDRIDE TRANSFER INDUCED BY TERTIARYLBUTYLCHLORIDE
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Adamantane was chlorinated, without chlorine, by tertiarybutylchloride and Lewis acids.The result with AlCl3 gives the best yield (90.5percent) and selectivity (95.4percent) in 1-chloroadamantane so far reported.The results are consistent with an hydride transfer mechanism.
- Jalal, R.,Gallo, R.
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p. 1697 - 1704
(2007/10/02)
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- A USEFUL METHOD FOR CONVERTING 2 ALCOHOLS TO THEIR CHLORIDES WITH RETENTION OF CONFIGURATION
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Xanthate esters of 2 alcohols are converted to their chlorides with retention of configuration in good yield by use of sulfuryl chloride.
- Kozikowski, A. P.,Lee, Jaemoon
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p. 3053 - 3056
(2007/10/02)
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- Kinetics of Ozonation. 6. Polycyclic Aliphatic Hydrocarbons.
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The reaction of ozone with norbornane, adamantane and bicyclooctane has been studied, including kinetics and product studies as well as the determination of activation paprameters for the ozonation of norbornane.This work was carried out to distinguish between hydride abstraction and a concerted insertion mechanism for the ozonation of C-H bonds.Kinetically, norbornane behaves like a secondary hydrocarbon and lacks the rate acceleration expected if a carbocation intermediate were involved in a hydride abstraction mechanism.We interpret this and other results as supporting a 1,3-dipolar insertion mechanism for the reaction of ozone with C-H bonds.
- Giamalva, David H.,Church, Daniel F.,Pryor, William A.
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p. 3429 - 3432
(2007/10/02)
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- Catalytic Homogeneous Functionalization of Adamantane. Influence of Electronic and Structural Features of the Metalloporphyrin Catalyst on Atom Transfer Selectivity (Oxygenation versus Azidification/Halogenation)
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Upon treatment of the two-phase systems, Mn tetraarylporphyrin, and alkane (organic phase)/Na+X- (aqueous phase), with iodosylarenes, both alcohols and alkyl azides (or halides), X- = halide or azide, are formed from the alkane substrates.The Mn porphyrin functions as a catalyst for alkane oxygenation and a phase transfer catalyst for X-.Catalytic functionalization of the exemplary caged alkane, adamantane, by a variety of these two-phase systems as function of the reaction conditions has been examined.The results reported here allow, for the first time, an assessment of the relathionship between the electronic and structural features of the metalloporphyrin catalysts and their selectivity with respect to the replacement of unactivated alkane carbon-hydrogen bonds with oxygen versus non-oxygen (halide or azide) functional groups.Of the first-row transition metal matalloporphyrins, only those of manganese are active for both the cleavage of unactivated alkane C-H bonds and replacement of these bonds by halogen or nitrogen-based groups.The oxygen donors that give the highest yields of these non-oxygenated products are the iodosylarenes.Examination of adamantane functionalization by iodosylarenes catalyzed by eight different manganese tetraphenylporphyrin derivatives, whose porphyrin ligands vary widely in electron-donating ability, establishes that the relative tertiary-secondary C-H cleavage selectivities are minimally affected by such electronic effects.In contrast, the selectivity for incorporation of the non-oxygen versus oxygen functions is substantially affected by the electron-donating ability of the catalyst porphyrin rings.The more electron withdrawing the porphyrin ring, and consequently the more anodic the potential of the ligated, S = 2, manganese(III) ion, the lower the selectivity for incorporation of the non-oxygen functions.Functionalization of adamantane catalyzed by the most electron poor manganese porphyrin complex, MnIII(F20TPP)X, is effectively selective for oxygenation.All the metalloporphyrins examined here eventually succumb to deactivation by irreversible oxidative degradation of the organic porphyrin ligand.
- Brown, Robert B.,Hill, Craig L.
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p. 5762 - 5768
(2007/10/02)
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- Cleavage of Tin-Carbon Bonds of Some Trimethylstannyl-adamantane Derivatives by Halogenating Agents
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2-Haloadamantanes (II, III) are obtained by the cleavage of Sn-C-bond of 2e-hydroxy-4e-(trimethylstannyl)adamantane (I) by PBr3/PBr5 and SOCl2.
- Islam, Md. Rabiul
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p. 576 - 577
(2007/10/02)
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- Synthese de quelques structures encombrees derivees de l'adamantane et de ses analogues par alkylation des ether d'enol trimethylsilyliques
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Alkylation of trimethylsilyl enol ethers of 2,4-dimethyl-3-pentanone, cyclopentanone and cyclohexanone has been extended to alkylating agents with a cage structure (substituted or functionalized adamantyl, diamantyl, homoadamantyl and noradamantyl chlorides or bromides).This method affords some new cage structured aliphatic and alicyclic ketones.In some cases one observes a new TiCl4 promoted reaction where the bromine in the alkylating agent is replaced by chlorine.This work is a generalization of our previous extended studies on α-alkylation of ketones with tertiary alkylating agents.
- Dubois, Jacques-Emile,Lebbar, Kadija,Lion, Claude,Dugast, Jean-Yves
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p. 905 - 910
(2007/10/02)
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- A NEW COMBINED OXIDIZING REAGENT SYSTEM, Fe(CH3CN)6(3+)-IO4(1-): OXIDATION OF PARAFFIN HYDROCARBONS
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Combined oxidizing reagent systems of Fe(AN)6ClO4)3 ( AN = acetonitrile ) with halogen oxyacids were investigated.In particular, reactions of paraffin hydrocarbons with a combined reagent system of Fe(AN)6(3+) were explored because of the high reactivity of this system in the oxidation of adamantane ( Table 1 ).Oxidation of bornane, norbornane, cyclohexane, and n-hexane gave the corresponding acetamides and acetates ( Tabla II ).These results shows that the title reagent system can efficiently oxidize organic substrates which have onset potentials of anodic current of ca. 2.7 V vs. saturated calomel electrode.Keywords - oxidation; paraffin hydrocarbon; combined reagent system; hexakisacetonitrile iron(III) perchlorate; halogen oxyacid; sodium periodate
- Kotani, Eiichi,Kobayashi, Shigeki,Ishii, Yoko,Tobinaga, Seisho
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p. 4680 - 4684
(2007/10/02)
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- High-Yield Direct Synthesis of a New Class of Tertiary Organolithium Derivatives of Polycyclic Hydrocarbons
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For the first time, 1- and 2-adamantyllithium, 1-diamantyllithium, 3,5,7-trimethyl-1-adamantyllithium, 1-twistyllithium, 3-methyl-7-noradamantyllithium, 1-triptycyllithium, and 3-homoadamantyllithium have been directly synthesized from the reaction of an organic halide and lithium metal.By use of certain experimental parameters, the phenomena at the metal-solution interface are controlled, thereby resulting in exceptionally high yields of this new class of organometallic compounds (>75percent, except in the case of 3-homoadamantyllithium).Competition between formation of the organometallic compound and formation of solvent-attack byproducts is determined by the degree of adsorption of the transient species (anion radical RX-. or radical pair R..Li) generated at the metal surface during attack by the halogenated derivative.
- Molle, G.,Bauer, P.,Dubois, J. E.
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p. 2975 - 2981
(2007/10/02)
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- MECHANISMS OF FREE-RADICAL REACTIONS. XV. SELECTIVITY OF THE FREE-RADICAL CHLORINATION OF ALIPHATIC HYDROCARBONS BY ARYLCHLOROIODONIUM CHLORIDES
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The free-radical chlorination of 2,3-dimethylbutane, 2,2,4-trimethylpentane, adamantane, and cyclohexane by arylchloroiodonium chlorides was investigated by the method of competing reactions.It was shown that the introduction of electron-withdrawing substituents into the arylchloroiodonium chloride leads to an increase in the sensitivity of the process to the polar effect of the substituents in the substrate and to a decrease of the selectivity toward variation in the dissociation energy of the C - H bond.The importance of steric effects in the reaction was noted.
- Dneprovskii, A. S.,Krainyuchenko, I. V.,Kasatochkin, A. N.
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p. 437 - 440
(2007/10/02)
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- Neighboring Group Effects in the β-Halo Amines. Synthesis and Solvolytic Reactivity of the anti-4-Substituted 2-Azaadamantyl System
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The syntheses of anti-4-chloro-2-n-propyl-2-azaadamantane (1) and 2-(2-chloroethyl)-2-azaadamantane (8) were carried out.When 1 was subjected to solvolysis in aqueous methanolic NaOH, a rate enhancement of ca. 2*106 was observed at 25 deg C, compared to that for 2-chloroadamantane (23).The solvolytic rate of 1 is comparable to that of an aliphatic β-halo amine, and because of the absence of a kinetic rate component due to solvent assistance in the adamantyl system, the observed enhancement may represent the rate-limiting case for the substituted β-chloroethylamines.The solvolysis rate of 8 was 2.5-fold less than that of 1, despite an expected decrease in activation energy.The lower rate for 8 may be due to its larger negative entropy of activation compared to that of 1.Indirect evidence was found for the existence of azridinium ion intermediates during solvolysis, but their direct observation remains to be accomplished.
- Henkel, James G.,Faith, William C.
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p. 4953 - 4959
(2007/10/02)
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- ELECTROPHILIC ATTACK OF ELEMENTAL FLUORINE ON ORGANIC HALOGENS. SYNTHESIS OF FLUOROADAMANTANES
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Elemental fluorine acts on bromo- and iodoadamantanes in an electrophilic mode to produce the corresponding fluoroadamantanes.The course of the reaction was investigated in several solvents.It was found that the best yields of the fluoroadamantanes were obtained when Freon (CFCl3) or Freon-chloroform was used.Using methylene chloride as a solvent with iodoadamantanes-but not with the bromo derivatives-resulted in considerable amounts of the corresponding chloro compounds.
- Rozen, Shlomo,Brand, Michael
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p. 733 - 736
(2007/10/02)
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- Triyclo3,7>decan (9-Homo-nor-adamantan) Synthese und Umwandlungen
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A synthesis of tricyclo3,7>decane (= 9-homo-nor-adamantane; 1), which belongs to the adamantaneland, a family of nineteen isomeric C10H16 hydrocarbons, is described, as well as derivatives thereof.Treatment of protoadamantan-5endo-ol (11) with either thionyl chloride or phosphorus pentachloride yielded under rearrangement the chloride 18, and solvolysis of the 5endo-chloroprotoadamantane (16) led to the acetate 26, 18 and 26 having both the tricyclo3,7>decane skeleton.Subsequent transformations gave the title compound 1 as well as the corresponding olefin 8.
- Jaeggi, Franz Josef,Ganter, Camille
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p. 2087 - 2095
(2007/10/02)
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