- Liquid-Phase Reactions of CCl3 Radicals with Trimethylsilane and Triethylsilane
-
The γ-radiation-induced chain reactions in liquid solution of silane (R'3SiH) in CCl4-c-C6H12(RH) mixtures were investigated over the temperature range 303-423 K for R' = Me and 335-423 K for R' = Et.In both systems the main products are R'3SiCl, CHCl3, and RCl.By kinetic analyses of product distribution, the rate constants of hydrogen abstraction from the two silanes by CCl3 radicals were competitively determined vs. hydrogen abstraction from cyclohexane.The relative rate constants combined with the known Arrhenius parameters of the reference systems gave the following Arrhenius parameters for the reaction CCl3 + R'3SiH -> CHCl3 + R'3Si: log A4 (L mol-1 s-1) = 8.49 and E4 = 8.70 kcal mol-1 when R' = Me, and log A4 = 8.62 and E4 = 8.06 when R' = Et.These results indicate that alkyl-substituted silanes are considerably more reactive than Cl3SiH in the H-atom transfer reactions with CCl3 radicals.This observation is rationalized in terms of the polar effects of the alkyl substituents.
- Baruch, G.,Horowitz, A.
-
-
Read Online
- Oxidative aromatization of olefins with dioxygen catalyzed by palladium trifluoroacetate
-
(Chemical Equation Presented) Molecular oxygen can replace sacrificial olefins as the hydrogen acceptor in the palladium trifluoroacetate catalyzed dehydrogenation of cyclohexene and related cyclic olefins into aromatics. One of the major drawbacks of the homogeneous system is the tendency of the palladium trifluoroacetate to precipitate as palladium(0) at elevated temperatures. The use of better ligands affords catalysts that can operate at higher temperatures, although they are less reactive than palladium trifluoroacetate.
- Bercaw, John E.,Hazari, Nilay,Labinger, Jay A.
-
-
Read Online
- Non-Heme-Iron-Mediated Selective Halogenation of Unactivated Carbon?Hydrogen Bonds
-
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
-
supporting information
(2021/12/09)
-
- Aerobic Partial Oxidation of Alkanes Using Photodriven Iron Catalysis
-
Photodriven oxidations of alkanes in trifluoroacetic acid using commercial and synthesized Fe(III) sources as catalyst precursors and dioxygen (O2) as the terminal oxidant are reported. The reactions produce alkyl esters and occur at ambient temperature in the presence of air, and catalytic turnover is observed for the oxidation of methane in a pure O2 atmosphere. Under optimized conditions, approximately 17% conversion of methane to methyl trifluoroacetate at more than 50% selectivity is observed. It is demonstrated that methyl trifluoroacetate is stable under catalytic conditions, and thus overoxidized products are not formed through secondary oxidation of methyl trifluoroacetate.
- Coutard, Nathan,Goldberg, Jonathan M.,Valle, Henry U.,Cao, Yuan,Jia, Xiaofan,Jeffrey, Philip D.,Gunnoe, T. Brent,Groves, John T.
-
p. 759 - 766
(2022/01/11)
-
- Enthalpy-Entropy Compensation Effect in Oxidation Reactions by Manganese(IV)-Oxo Porphyrins and Nonheme Iron(IV)-Oxo Models
-
"Enthalpy-Entropy Compensation Effect"(EECE) is ubiquitous in chemical reactions; however, such an EECE has been rarely explored in biomimetic oxidation reactions. In this study, six manganese(IV)-oxo complexes bearing electron-rich and -deficient porphyrins are synthesized and investigated in various oxidation reactions, such as hydrogen atom transfer (HAT), oxygen atom transfer (OAT), and electron-transfer (ET) reactions. First, all of the six Mn(IV)-oxo porphyrins are highly reactive in the HAT, OAT, and ET reactions. Interestingly, we have observed a reversed reactivity in the HAT and OAT reactions by the electron-rich and -deficient Mn(IV)-oxo porphyrins, depending on reaction temperatures, but not in the ET reactions; the electron-rich Mn(IV)-oxo porphyrins are more reactive than the electron-deficient Mn(IV)-oxo porphyrins at high temperature (e.g., 0 °C), whereas at low temperature (e.g., -60 °C), the electron-deficient Mn(IV)-oxo porphyrins are more reactive than the electron-rich Mn(IV)-oxo porphyrins. Such a reversed reactivity between the electron-rich and -deficient Mn(IV)-oxo porphyrins depending on reaction temperatures is rationalized with EECE; that is, the lower is the activation enthalpy, the more negative is the activation entropy, and vice versa. Interestingly, a unified linear correlation between the activation enthalpies and the activation entropies is observed in the HAT and OAT reactions of the Mn(IV)-oxo porphyrins. Moreover, from the previously reported HAT reactions of nonheme Fe(IV)-oxo complexes, a linear correlation between the activation enthalpies and the activation entropies is also observed. To the best of our knowledge, we report the first detailed mechanistic study of EECE in the oxidation reactions by synthetic high-valent metal-oxo complexes.
- Guo, Mian,Zhang, Jisheng,Zhang, Lina,Lee, Yong-Min,Fukuzumi, Shunichi,Nam, Wonwoo
-
supporting information
p. 18559 - 18570
(2021/11/22)
-
- Site Selective Chlorination of C(sp3)?H Bonds Suitable for Late-Stage Functionalization
-
C(sp3)?Cl bonds are present in numerous biologically active small molecules, and an ideal route for their preparation is by the chlorination of a C(sp3)?H bond. However, most current methods for the chlorination of C(sp3)?H bonds are insufficiently site selective and tolerant of functional groups to be applicable to the late-stage functionalization of complex molecules. We report a method for the highly selective chlorination of tertiary and benzylic C(sp3)?H bonds to produce the corresponding chlorides, generally in high yields. The reaction occurs with a mixture of an azidoiodinane, which generates a selective H-atom abstractor under mild conditions, and a readily-accessible and inexpensive copper(II) chloride complex, which efficiently transfers a chlorine atom. The reaction's exceptional functional group tolerance is demonstrated by the chlorination of >30 diversely functionalized substrates and the late-stage chlorination of a dozen derivatives of natural products and active pharmaceutical ingredients.
- Fawcett, Alexander,Keller, M. Josephine,Herrera, Zachary,Hartwig, John F.
-
supporting information
p. 8276 - 8283
(2021/03/15)
-
- Photocatalytic C-H activation and the subtle role of chlorine radical complexation in reactivity
-
The functionalization of methane, ethane, and other alkanes derived from fossil fuels is a central goal in the chemical enterprise. Recently, a photocatalytic system comprising [CeIVCl5(OR)]2- [CeIV, cerium(IV); OR, -OCH3 or -OCCl2CH3] was disclosed. The system was reportedly capable of alkane activation by alkoxy radicals (RO·) formed by CeIV-OR bond photolysis. In this work, we present evidence that the reported carbon-hydrogen (C-H) activation of alkanes is instead mediated by the photocatalyst [NEt4]2[CeCl6] (NEt4+, tetraethylammonium), and RO· are not intermediates. Spectroscopic analyses and kinetics were investigated for C-H activation to identify chlorine radical (Cl·) generation as the ratelimiting step. Density functional theory calculations support the formation of [Cl·][alcohol] adducts when alcohols are present, which can manifest a masked RO· character. This result serves as an important cautionary note for interpretation of radical trapping experiments.
- Yang, Qiaomu,Wang, Yu-Heng,Qiao, Yusen,Gau, Michael,Carroll, Patrick J.,Walsh, Patrick J.,Schelter, Eric J.
-
p. 847 - 852
(2021/05/28)
-
- Revisiting Alkane Hydroxylation with m-CPBA (m-Chloroperbenzoic Acid) Catalyzed by Nickel(II) Complexes
-
Mechanistic studies are performed on the alkane hydroxylation with m-CPBA (m-chloroperbenzoic acid) catalyzed by nickel(II) complexes, NiII(L). In the oxidation of cycloalkanes, NiII(TPA) acts as an efficient catalyst with a high yield and a high alcohol selectivity. In the oxidation of adamantane, the tertiary carbon is predominantly oxidized. The reaction rate shows first-order dependence on [substrate] and [NiII(L)] but is independent on [m-CPBA]; vobs=k2[substrate][NiII(L)]. The reaction exhibited a relatively large kinetic deuterium isotope effect (KIE) of 6.7, demonstrating that the hydrogen atom abstraction is involved in the rate-limiting step of the catalytic cycle. Furthermore, NiII(L) supported by related tetradentate ligands exhibit apparently different catalytic activity, suggesting contribution of the NiII(L) in the catalytic cycle. Based on the kinetic analysis and the significant effects of O2 and CCl4 on the product distribution pattern, possible contributions of (L)NiII?O. and the aroyloxyl radical as the reactive oxidants are discussed.
- Itoh, Mayu,Itoh, Shinobu,Kubo, Minoru,Morimoto, Yuma,Shinke, Tomoya,Sugimoto, Hideki,Wada, Takuma,Yanagisawa, Sachiko
-
p. 14730 - 14737
(2021/09/29)
-
- Aliphatic C–H hydroxylation activity and durability of a nickel complex catalyst according to the molecular structure of the bis(oxazoline) ligands
-
Applicability of the oxazoline-based compounds, bis(2-oxazolynyl)methane (BOX) and 2,6-bis(2-oxazolynyl)pyridine (PyBOX), as supporting ligands of nickel(II) complexes for the catalysis of aliphatic C–H hydroxylation with m-CPBA (meta-chloroperoxybenzoic acid) was explored. Substituent groups at the fourth and fifth positions of oxazoline rings and the bridgehead carbon atom of the BOX derivatives affected the catalytic performances toward cyclohexane hydroxylation. Presence of dioxygen led to a reduced catalytic performance of the nickel complexes, except in the case of a fully substituted BOX ligand complex.
- Hikichi, Shiro,Izumi, Takashi,Matsuba, Naki,Nakazawa, Jun
-
-
- Mechanism of Ni-catalyzed oxidations of unactivated C(sp3)-H Bonds
-
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)
-
- Thiourea-Mediated Halogenation of Alcohols
-
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
-
supporting information
p. 12901 - 12911
(2020/11/26)
-
- Efficient alkane hydroxylation catalysis of nickel(ii) complexes with oxazoline donor containing tripodal tetradentate ligands
-
Tris(oxazolynylmethyl)amine TOAR(where R denotes the substituent groups on the fourth position of the oxazoline rings) complexes of nickel(ii) have been synthesized as catalyst precursors for alkane oxidation withmeta-chloroperoxybenzoic acid (m-CPBA). The molecular structures of acetato, nitrato,meta-chlorobenzoato and chlorido complexes with TOAMe2have been determined using X-ray crystallography. The bulkiness of the substituent groups R affects the coordination environment of the nickel(ii) centers, as has been demonstrated by comparison of the molecular structures of chlorido complexes with TOAMe2and TOAtBu. The nickel(ii)-acetato complex with TOAMe2is an efficient catalyst precursor compared with the tris(pyridylmethyl)amine (TPA) analogue. Oxazolynyl donors’ strong s-electron donating ability will enhance the catalytic activity. Catalytic reaction rates and substrate oxidizing position selectivity are controlled by the structural properties of the R of TOAR. Reaction of the acetato complex with TOAMe2andm-CPBA yields the corresponding acylperoxido species, which can be detected using spectroscopy. Kinetic studies of the decay process of the acylperoxido species suggest that the acylperoxido species is a precursor of an active species for alkane oxidation.
- Hikichi, Shiro,Horii, Sena,Nakazawa, Jun,Okamura, Masaya,Terao, Ikumi
-
supporting information
p. 6108 - 6118
(2020/05/25)
-
- Ferric chloride–catalyzed deoxygenative chlorination of carbonyl compounds: A comparison of chlorodimethylsilane and dichloromethylsilane system
-
Deoxygenative chlorination of carbonyl compounds using the HMe2SiCl/FeCl3/EtOAc and HMeSiCl2/FeCl3/EtOAc systems has been systemically investigated. The HMe2SiCl-FeCl3 system showed the advantages of good substrate applicability, mild reaction conditions, simple operation, low cost, and easy availability of raw materials. Also, it provided a simple and efficient synthesis route for carbonyl deoxychlorination via a one-pot method. Using the HMeSiCl2/FeCl3/EtOAc system, the β-methylchalcone derivative could be obtained in good yields in addition to obtaining the chlorinated compound. Finally, two plausible reaction routes were proposed to describe the formation of the chlorinated compound and the β-methylchalcone derivative.
- Xing, Bing-Han,Zhao, Xuan-Xuan,Qin, Yu-Jun,Zhang, Pu,Guo, Zhi-Xin
-
p. 667 - 675
(2020/05/22)
-
- HCl and O2 co-activated bis(8-quinolinolato) oxovanadium(iv) complexes as efficient photoactive species for visible light-driven oxidation of cyclohexane to KA oil
-
This paper reports three bis(8-quinolinolato) oxovanadium(iv) complexes that are active for visible light-induced cyclohexane oxygenation under O2 (1 atm) in acetonitrile with HCl participation, achieving greater than 18% conversion and 86% selectivity for KA oil (cyclohexanone and cyclohexanol), along with a small amount of chlorinated product. Notably, these VIVOQ2 complexes are not only basically comparable to VIVO(acac)2 and some typical VV-compounds in photocatalytic activity but are also more selective for KA oil. Spectral characterizations (XPS, FT-IR and UV-vis) and DFT calculations support that VIVOQ2 complexes can be co-activated by HCl and O2 to form the VVO(OH)-containing photoactive (PA) species with one pendant ligand's phenoxyl radical and an axially coordinated chlorine, which are responsible for the present photocatalytic oxidation. Noteworthily, increasing the Cl-substituents of VIVOQ2 complexes and especially the amount of water in the reaction system obviously decelerated the generation of such PA species, which significantly improved the selectivity for KA oil.
- She, Jialuo,Lin, Xiangfeng,Fu, Zaihui,Li, Jianwei,Tang, Senpei,Lei, Ming,Zhang, Xin,Zhang, Chao,Yin, Dulin
-
p. 275 - 285
(2019/01/28)
-
- Heteroatom-induced band-reconstruction of metal vanadates for photocatalytic cyclohexane oxidation towards KA-oil selectivity
-
Structure-function correlation constitutes a central theme in the selective photocatalytic oxidation of cyclohexane with molecular oxygen, as a result of precise tailoring band-structure towards KA-oil selectivity. Herein, we comparatively and systematically investigate the correlation among optical properties, electronic structure, and photocatalytic performance of two d°-vanadate photocatalysts (BiVO4 and Cu3V2O8) using theoretical calculations and experimental techniques. Results show that BiVO4 promotes the selective oxidation pathway under visible-light irradiation with higher efficiency (TOF = 7.5 h?1, based on the molar amount of V sites) and chemoselectivity (cyclohexanone/cyclohexanol molar ratio = 3.0) than the Cu3V2O8. Meanwhile, the photocatalytic performance of BiVO4 demonstrates high photocatalytic selectivity towards KA-oil (95%), while Cu3V2O8 seems to facilitate the accommodation of chlorine promoters, leading to very different chlorocyclohexane selectivity (46%). Such the distinct photocatalytic performances of BiVO4 and Cu3V2O8 can be ascribed to their unique electronic structures to facilitate the e??h+ charge carriers and generation of reactive species during photoirradiation. The Bi3+ 6p states of BiVO4 are predominant components of the conduction band minimum (CBM) and hybridize with Bi3+ 6 s, and O2? 2p and V5+ 3d orbitals at the valence band maximum (VBM); whereas the Cu2+ 3d and V5+ 3d orbitals contribute to the CBM of Cu3V2O8, and Cu2+ 3d, O2? 2p and V5+ 3d orbitals at the VBM. So BiVO4 with s ? p matrix elements is more effective than the Cu3V2O8 in producing [rad]OH, h+ and H2O2, which can rapidly oxidize the C ? Cl band cleavage for chlorocyclohexane intermediate to regenerate newly Cl[rad] radicals in the next cycle reactions. Heteroatom-tuning of photocatalytic performance is further supported by universal evidences from experimental results by replacing Bi or Cu of the above vanadates with Ag, La, Sr, Fe or Ti atom and the study of the electrons, holes and radicals mediated reaction pathway by scavengers, respectively.
- Xiang, Liping,Fan, Jingjing,Zhong, Wenzhou,Mao, Liqiu,You, Kuiyi,Yin, Dulin
-
p. 120 - 131
(2019/02/25)
-
- N -Hydroxyphthalimide/benzoquinone-catalyzed chlorination of hydrocarbon C-H bond using N -chlorosuccinimide
-
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)
-
- Identifying Amidyl Radicals for Intermolecular C-H Functionalizations
-
Recent studies have demonstrated the capabilities of amidyl radicals to facilitate a range of intermolecular functionalizations of unactivated, aliphatic C-H bonds. Relatively little information is known regarding the important structural and electronic features of amidyl and related radicals that impart efficient reactivity. Herein, we evaluate a diverse range of nitrogen-centered radicals in unactivated, aliphatic C-H chlorinations. These studies establish the salient features of nitrogen-centered radicals critical to these reactions in order to expedite the future development of new site-selective, intermolecular C-H functionalizations.
- Tierney, Matthew M.,Crespi, Stefano,Ravelli, Davide,Alexanian, Erik J.
-
p. 12983 - 12991
(2019/10/02)
-
- Heteroleptic cobalt(iii) acetylacetonato complexes with N-heterocyclic carbine-donating scorpionate ligands: Synthesis, structural characterization and catalysis
-
Exposure of O2 to a reaction mixture containing bis(acac)cobalt(ii), a facially capping tris(N-heterocyclic carbene)borate ligand and 1-methylimidazole yields a heteroleptic cobalt(iii) complex with acac, 1-methylimidazole and tris(NHC)borate ligands. meta-Chloroperbenzoic acid is efficiently activated by this heteroleptic complex to catalytically oxidize cyclohexane at ambient temperature.
- Nishiura, Toshiki,Takabatake, Asako,Okutsu, Mariko,Nakazawa, Jun,Hikichi, Shiro
-
supporting information
p. 2564 - 2568
(2019/02/27)
-
- Organocatalytic Chlorination of Alcohols by P(III)/P(V) Redox Cycling
-
A catalytic system for the chlorination of alcohols under Appel conditions was developed. Benzotrichloride is used as a cheap and readily available chlorinating agent in combination with trioctylphosphane as the catalyst and phenylsilane as the terminal reductant. The reaction has several advantages over other variants of the Appel reaction, e.g., no additional solvent is required and the phosphane reagent is used only in catalytic amounts. In total, 27 different primary, secondary, and tertiary alkyl chlorides were synthesized in yields up to 95%. Under optimized conditions, it was also possible to convert epoxides and an oxetane to the dichlorinated products.
- Longwitz, Lars,Jopp, Stefan,Werner, Thomas
-
p. 7863 - 7870
(2019/06/27)
-
- Selective C-H halogenation over hydroxylation by non-heme iron(iv)-oxo
-
Non-heme iron based halogenase enzymes promote selective halogenation of the sp3-C-H bond through iron(iv)-oxo-halide active species. During halogenation, competitive hydroxylation can be prevented completely in enzymatic systems. However, synthetic iron(iv)-oxo-halide intermediates often result in a mixture of halogenation and hydroxylation products. In this report, we have developed a new synthetic strategy by employing non-heme iron based complexes for selective sp3-C-H halogenation by overriding hydroxylation. A room temperature stable, iron(iv)-oxo complex, [Fe(2PyN2Q)(O)]2+ was directed for hydrogen atom abstraction (HAA) from aliphatic substrates and the iron(ii)-halide [FeII(2PyN2Q)(X)]+ (X, halogen) was exploited in conjunction to deliver the halogen atom to the ensuing carbon centered radical. Despite iron(iv)-oxo being an effective promoter of hydroxylation of aliphatic substrates, the perfect interplay of HAA and halogen atom transfer in this work leads to the halogenation product selectively by diverting the hydroxylation pathway. Experimental studies outline the mechanistic details of the iron(iv)-oxo mediated halogenation reactions. A kinetic isotope study between PhCH3 and C6D5CD3 showed a value of 13.5 that supports the initial HAA step as the RDS during halogenation. Successful implementation of this new strategy led to the establishment of a functional mimic of non-heme halogenase enzymes with an excellent selectivity for halogenation over hydroxylation. Detailed theoretical studies based on density functional methods reveal how the small difference in the ligand design leads to a large difference in the electronic structure of the [Fe(2PyN2Q)(O)]2+ species. Both experimental and computational studies suggest that the halide rebound process of the cage escaped radical with iron(iii)-halide is energetically favorable compared to iron(iii)-hydroxide and it brings in selective formation of halogenation products over hydroxylation.
- Rana, Sujoy,Biswas, Jyoti Prasad,Sen, Asmita,Clémancey, Martin,Blondin, Geneviève,Latour, Jean-Marc,Rajaraman, Gopalan,Maiti, Debabrata
-
p. 7843 - 7858
(2018/10/31)
-
- Aliphatic C-H Bond Halogenation by Iron(II)-α-Keto Acid Complexes and O2: Functional Mimicking of Nonheme Iron Halogenases
-
α-Ketoglutarate-dependent nonheme halogenases catalyze the halogenation of aliphatic C-H bonds in the biosynthesis pathway of many natural products. An iron(IV)-oxo-halo species has been established as the active oxidant in the halogenation reactions. With an objective to emulate the function of the nonheme halogenases, two iron(II)-α-keto acid complexes, [(phdpa)Fe(BF)Cl] (1) and [(1,4-tpbd)Fe2(BF)2Cl2] (2) (where phdpa = N,N-bis(2-pyridylmethyl)aniline, 1,4-tpbd = N,N,N′,N'-tetrakis(2-pyridylmethyl)benzene-1,4-diamine, and BF = benzoylformate), have been prepared. The iron complexes are capable of carrying out the oxidative halogenation of aliphatic C-H bonds using O2 as the terminal oxidant. Although the complexes are not selective toward C-H bond halogenation, they are the only examples of nonheme iron(II)-α-keto acid complexes mimicking the activity of nonheme halogenases. The dinuclear complex (2) exhibits enhanced reactivity toward C-H bond halogenation/hydroxylation.
- Jana, Rahul Dev,Sheet, Debobrata,Chatterjee, Sayanti,Paine, Tapan Kanti
-
p. 8769 - 8777
(2018/08/17)
-
- Highly selective halogenation of unactivated C(sp3)-H with NaX under co-catalysis of visible light and Ag@AgX
-
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
-
p. 4729 - 4737
(2018/10/23)
-
- Experimental and theoretical studies of a greener catalytic system for saturated hydrocarbon chlorination composed by trichloroisocyanuric acid and a copper(II) compound
-
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
-
p. 150 - 158
(2018/06/14)
-
- Cobalt(II) complexes with N,N,N-scorpionates and bidentate ligands: Comparison of hydrotris(3,5-dimethylpyrazol-1-yl)borate Tp? vs. Phenyltris(4,4-dimethyloxazolin-2-yl)borate ToM to control the structural properties and reactivities of cobalt centers
-
Scorpionate ligands Tp? (hydrotris(3,5-dimethylpyrazol-1-yl)borate) and ToM (tris(4,4- dimethyloxazolin-2-yl)phenylborate) complexes of cobalt(II) with bidentate ligands were synthesized. Both Tp? and ToM coordinate to cobalt(II) in a tridentate fashion when the bidentate ligand is the less hindered acetylacetonate. In crystal structures, the geometry of cobalt(II) supported by the N3O2 donor set in the Tp? complex is a square-pyramid, whereas that in the ToM complex is close to a trigonal-bipyramid. Both Tp?- and ToM-acac complexes exhibit solvatochromic behavior, although the changing structural equilibria of these complexes in MeCN are quite different. In the bis(1-methylimidazol-2-yl)methylphenylborate (LPh) complexes, Tp? retains the tridentate (k3) mode, whereas ToM functions as the bidentate (k2) ligand, giving the tetrahedral cobalt(II) complex. The bowl-shaped cavity derived from the six methyl groups on ToM lead to susceptibility to the bulkiness of the opposite bidentate ligand. The entitled scorpionate compounds mediate hydrocarbon oxidation with organic peroxides. Allylic oxidation of cyclohexene occurs mainly on the reaction with tert-butyl hydroperoxide (TBHP), although the catalytic efficiency of the scorpionate ligand complexes is lower than that of Co(OAc)2 and Co(acac)2. On cyclohexane oxidation with meta-chloroperbenzoic acid (mCPBA), both ToM and Tp? complexes function as catalysts for hydroxylation. The higher electron-donating ToM complexes show faster initial reaction rates compared to the corresponding Tp? complexes.
- Nishiura, Toshiki,Uramoto, Takahiro,Takiyama, Yuichiro,Nakazawa, Jun,Hikichi, Shiro
-
-
- Photoreduction of Thioether Gold(III) Complexes: Mechanistic Insight and Homogeneous Catalysis
-
Complexes formed between AuCl3 and thioether ligands underwent a photoinduced reductive elimination under homogeneous conditions in dichloromethane and toluene solutions to afford the corresponding AuI complexes. All the gold(III) complexes were rapidly reduced to the gold(I) chloride complexes under 365 nm irradiation or ambient light while being thermally stable below 55 °C. The mechanism of photoreduction through Cl2 elimination is discussed based on a kinetic study and the chemical trapping of chlorine species: Cl2, radical Cl., and possibly Cl+. The catalytic activities of the gold(III) chloride complexes and the corresponding gold(I) complexes obtained by in situ reduction were evaluated in the cyclization of N-propargylic amides to oxazoles. The merits of such photoreducible complexes in homogeneous gold catalysis are illustrated by a cascade reaction catalyzed by thioether gold complexes that affords a 4H-quinolizin-4-one in high yields.
- Cao, Zhen,Bassani, Dario M.,Bibal, Brigitte
-
supporting information
p. 18779 - 18787
(2018/11/23)
-
- Copper(II) Complexes with Bulky N-Substituted Diethanolamines: High-Field Electron Paramagnetic Resonance, Magnetic, and Catalytic Studies in Oxidative Cyclohexane Amidation
-
The novel coordination compounds [Cu2(HtBuDea)2(OAc)2] (1) and [Cu2(HnBuDea)2Cl2]·nH2O (2) have been prepared through the reaction of the respective copper(II) salts with N-tert-butyldiethanolamine (H2tBuDea, for 1) or N-butyldiethanolamine (H2nBuDea, for 2) in methanol solution. Crystallographic analysis reveals that, in spite of the common binuclear {Cu2(μ-O)2} core, the supramolecular structures of the complexes are drastically different. In 1 binuclear molecules are linked together by H-bonds into 1D chains, while in 2 the neighboring pairs of binuclear molecules are H-bonded, forming tetranuclear aggregates. Variable-temperature (1.8-300 K) magnetic susceptibility measurements of 1 and 2 show a dominant antiferromagnetic behavior. Both complexes are also studied by HF-EPR spectroscopy. While the interaction between Cu(II) centers in 1 can be described by a single coupling constant J = 130.1(3) cm-1 (using H = JS1S2), the crystallographically different {Cu2(μ-O)2} pairs in 2 are expected exchange from ferro- to antiferromagnetic behavior (with J ranging from -32 to 110 cm-1, according to DFT calculations). Complexes 1 and 2 act as catalysts in the amidation of cyclohexane with benzamide, employing tBuOOtBu as oxidant. The maximum achieved conversion of benzamide (20%, after 24 h reaction time) was observed in the 1/tBuOOtBu system. In the cases of tBuOO(O)CPh or tBuOOH oxidants, no significant amidation product was observed, while for tBuOO(O)CPh, the oxidative dehydrogenation of cyclohexane occurred, giving cyclohexene, to afford the allylic ester (cyclohex-2-en-1-yl benzoate) as the main reaction product.
- Nesterova, Oksana V.,Nesterov, Dmytro S.,Jezierska, Julia,Pombeiro, Armando J. L.,Ozarowski, Andrew
-
p. 12384 - 12397
(2018/09/25)
-
- Mysterious Decomposition of Alkoxyphosphonium Chlorides: Postulated Involvement of the HCl2 Anion and Its Capture in the Solid State
-
P-Alkoxyphosphonium (AP) chlorides were generated by reacting P-chlorophosphonium chlorides with alcohols. Their well-known spontaneous Arbuzov-type collapse leading to phosphine oxides was studied and its rate found to be dependent on a number of factors in an unexpected fashion: it is inversely proportional to the initial concentration and it shows strong dependence on the acidity of the media but is not very sensitive to the presence of base. To explain these observations, we evoke a self-inhibition model with the formation of the less nucleophilic hydrodichloride anion HCl2 in solution. Detailed analysis of the kinetic data yields the association constant (K=3×102 m?1) of the putative HCl2 species in chloroform. Experimental observations for the collapse of highly enriched diastereomeric alkoxyphosphonium (DAP) chlorides are fully analogous to the achiral AP also implying the involvement of HCl2 anions. Moreover, crystallisation of a highly enriched DAP salt derived from (?)-menthol furnished, for the first time, crystals of individual (RP)-DAP hydrodichloride as confirmed by X-ray diffractometry. Importantly, the P-configuration and detailed conformation of the DAP moiety is in good agreement with DFT-level computational results. The thermal collapse of (RP)-DAP?HCl2 proceeds with complete retention of the P-configuration furnishing the phosphine oxide of exceptional enantiomeric purity.
- Nikitin, Kirill,Müller-Bunz, Helge,Muldoon, Jimmy,Gilheany, Declan G.
-
p. 4794 - 4802
(2017/04/14)
-
- A alkane halogenation method (by machine translation)
-
The invention relates to a cycloalkane of halogenation method, comprises the following steps: S1: taking inorganic hydrohalide salt M+ X- And the inorganic acid or organic acid, stirring to dissolve in water, containing the halide X- Aqueous solution; S2: light in the reactor will be put aqueous solution, add nanometer metal/semiconductor composite material photocatalyst, phase transfer catalyst and reaction substrate cycloalkane; S3: under the stirring condition, in the sunlight or 300W xenon lamp or LED light shifted to catalytic reaction; S4: reaction after the fluid is static set, filtering and recycling photocatalyst, separating and recovering the aqueous phase and then, drying the organic phase, and the dried organic phase rectification separation purification, to obtain the corresponding organic halogenated product. The present invention provides a method halide of the cycloalkanes, low cost, the apparatus is simple and easy to operate, high selectivity, easy separation, can be large-scale production, is a novel, environmental protection, high selectivity, low energy consumption of the new organic halide, viable green channels, with potential industrial application value. (by machine translation)
- -
-
Paragraph 0031-0037; 0048; 0049
(2017/07/21)
-
- A base-resistant metalloporphyrin metal-organic framework for C-H bond halogenation
-
A base-resistant porphyrin metal-organic framework (MOF), namely PCN-602 has been constructed with 12-connected LNi8(OH)4(H2O)2Pz12] (Pz = pyrazolate) cluster and a newly designed Pyrazolate-based porphyrin ligand, 5, 10, 15, 20-tetrakis(4-(pyrazolate-4-yl)-phenyl)porphyrin under the guidance of the reticular synthesis strategy. Besides its robustness in hydroxide solution, PCN-602 also shows excellent stability in aqueous solutions of F-, CO,2-, and PO43- ions. Interestingly, the Mn3+-porphyrinic PCN-602, as a recyclable MOF catalyst, presents high catalytic activity for the C-H bond halogenation reaction in a basic system, significantly outperforming its homogeneous counterpart. For the first time, a porphyrinic MOF was thus used as an efficient catalyst in a basic solution with coordinating anions, to the best of our knowledge.
- Lv, Xiu-Liang,Wang, Kecheng,Wang, Bin,Su, Jie,Zou, Xiaodong,Xie, Yabo,Li, Jian-Rong,Zhou, Hong-Cai
-
supporting information
p. 211 - 217
(2017/05/16)
-
- Visible Light-Induced Oxidative Chlorination of Alkyl sp3 C-H Bonds with NaCl/Oxone at Room Temperature
-
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)
-
- Mild Aliphatic and Benzylic Hydrocarbon C-H Bond Chlorination Using Trichloroisocyanuric Acid
-
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.
-
p. 2407 - 2413
(2017/03/11)
-
- Modeling Non-Heme Iron Halogenases: High-Spin Oxoiron(IV)-Halide Complexes That Halogenate C-H Bonds
-
The non-heme iron halogenases CytC3 and SyrB2 catalyze C-H bond halogenation in the biosynthesis of some natural products via S = 2 oxoiron(IV)-halide intermediates. These oxidants abstract a hydrogen atom from a substrate C-H bond to generate an alkyl radical that reacts with the bound halide to form a C-X bond chemoselectively. The origin of this selectivity has been explored in biological systems but has not yet been investigated with synthetic models. Here we report the characterization of S = 2 [FeIV(O)(TQA)(Cl/Br)]+ (TQA = tris(quinolyl-2-methyl)amine) complexes that can preferentially halogenate cyclohexane. These are the first synthetic oxoiron(IV)-halide complexes that serve as spectroscopic and functional models for the halogenase intermediates. Interestingly, the nascent substrate radicals generated by these synthetic complexes are not as short-lived as those obtained from heme-based oxidants and can be intercepted by O2 to prevent halogenation, supporting an emerging notion that rapid rebound may not necessarily occur in non-heme oxoiron(IV) oxidations.
- Puri, Mayank,Biswas, Achintesh N.,Fan, Ruixi,Guo, Yisong,Que, Lawrence
-
p. 2484 - 2487
(2016/03/12)
-
- Design and synthesis of a dinucleating ligand system with varying terminal donor functions that provides no bridging donor and its application to the synthesis of a series of FeIII-μ-O-FeIII complexes
-
Based on a rational ligand design for stabilizing high-valent {Fe(μ-O)2Fe} cores, a new family of dinucleating bis(tetradentate) ligands with varying terminal donor functions has been developed: redox-inert biomimetic carboxylates in H4julia, pyridines in susan, and phenolates in H4hilde Me2. Based on a retrosynthetic analysis, the ligands were synthesized and used for the preparation of their diferric complexes [(julia){Fe(OH2)(μ-O)Fe(OH2)}]·6H2O, [(julia){Fe(OH2)(μ-O)Fe(OH2)}]·7H2O, [(julia){Fe(DMSO)(μ-O)Fe(DMSO)}]·3DMSO, [(hilde Me2){Fe(μ-O)Fe}]·CH2Cl2, [(hilde Me2){FeCl}2]·2CH2Cl2, [(susan){FeCl(μ-O)FeCl}]Cl2·2H2O, [(susan){FeCl(μ-O)FeCl0.75(OCH3)0.25}](ClO4)2·0.5MeOH, and [(susan){FeCl(μ-O)FeCl}](ClO4)2·0.5EtOH, which were characterized by single-crystal X-ray diffraction, FTIR, UV-Vis-NIR, M?ssbauer, magnetic, and electrochemical measurements. The strongly electron-donating phenolates afford five-coordination, while the carboxylates and pyridines lead to six-coordination. The analysis of the ligand conformations demonstrates a strong flexibility of the ligand backbone in the complexes. The different hydrogen-bonding in the secondary coordination sphere of [(julia){Fe(OH2)(μ-O)Fe(OH2)}] influences the C-O, CO, and Fe-O bond lengths and is reflected in the FTIR spectra. The physical properties of the central {Fe(μ-O)Fe} core (d-d, μ-oxo → FeIII CT, νas(Fe-O-Fe), J) are governed by the differences in terminal ligands-FeIII bonds: strongly covalent π-donation with phenolates, less covalent π-donation with carboxylates, and π-acceptation with pyridines. Thus, [(susan){FeCl(μ-O)FeCl}]2+ is oxidized at 1.48 V vs. Fc+/Fc, which is shifted to 1.14 V vs. Fc+/Fc by methanolate substitution, while [(julia){Fe(OH2)(μ-O)Fe(OH2)}] is oxidized ≤1 V vs. Fc+/Fc. [(hilde Me2){Fe(μ-O)Fe}] is oxidized at 0.36 V vs. Fc+/Fc to a phenoxyl radical. The catalytic oxidation of cyclohexane with TONs up to 39.5 and 27.0 for [(susan){FeCl(μ-O)FeCl}]2+ and [(hilde Me2){Fe(μ-O)Fe}], respectively, indicates the potential to form oxidizing intermediates.
- Strautmann, Julia Bernhardette Hildegard,Dammers, Susanne,Limpke, Thomas,Parthier, Janine,Zimmermann, Thomas Philipp,Walleck, Stephan,Heinze-Brückner, Gabriele,Stammler, Anja,B?gge, Hartmut,Glaser, Thorsten
-
p. 3340 - 3361
(2016/03/05)
-
- A mild method for the replacement of a hydroxyl group by halogen. 1. Scope and chemoselectivity
-
α-Chloro-, bromo- and iodoenamines, which are readily prepared from the corresponding isobutyramides have been found to be excellent reagents for the transformation of a wide variety of alcohols or carboxylic acids into the corresponding halides. Yields are high and conditions are very mild thus allowing for the presence of sensitive functional groups. The reagents can be easily tuned allowing therefore the selective monohalogenation of polyhydroxylated molecules. The scope and chemoselectivity of the reactions have been studied and reaction mechanisms have been proposed.
- Munyemana, Fran?ois,George, Isabelle,Devos, Alain,Colens, Alain,Badarau, Eduard,Frisque-Hesbain, Anne-Marie,Loudet, Aurore,Differding, Edmond,Damien, Jean-Marie,Rémion, Jeanine,Van Uytbergen, Jacqueline,Ghosez, Léon
-
p. 420 - 430
(2015/12/31)
-
- Hydrogen Chloride Gas in Solvent-Free Continuous Conversion of Alcohols to Chlorides in Microflow
-
Chlorides represent a class of valuable intermediates that are utilized in the preparation of bulk and fine chemicals. An earlier milestone to convert bulk alcohols to corresponding chlorides was reached when hydrochloric acid was used instead of toxic and wasteful chlorinating agents. This paper presents the development of an intensified solvent-free continuous process by using hydrogen chloride gas only. The handling of corrosive hydrogen chloride became effortless when the operating platform was split into dry and wet zones. The dry zone is used to deliver gas and prevent corrosion, while the wet zone is used to carry out the chemical transformation. The use of gas instead of hydrochloric acid allowed a decrease in hydrogen chloride equivalents from 3 to 1.2. In 20 min residence time, full conversion of benzyl alcohol yielded 96 wt % of benzyl chloride in the product stream. According to green chemistry and engineering principles, the developed process is of an exemplary type due to its truly continuous nature, no use of solvent and formation of water as a sole byproduct.
- Borukhova, Svetlana,No?l, Timothy,Hessel, Volker
-
supporting information
p. 568 - 573
(2016/03/04)
-
- Site-Selective Aliphatic C-H Chlorination Using N-Chloroamides Enables a Synthesis of Chlorolissoclimide
-
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.
-
supporting information
p. 696 - 702
(2016/02/03)
-
- Continuous-Flow Multistep Synthesis of Cinnarizine, Cyclizine, and a Buclizine Derivative from Bulk Alcohols
-
Cinnarizine, cyclizine, buclizine, and meclizine belong to a family of antihistamines that resemble each other in terms of a 1-diphenylmethylpiperazine moiety. We present the development of a four-step continuous process to generate the final antihistamines from bulk alcohols as the starting compounds. HCl is used to synthesize the intermediate chlorides in a short reaction time and excellent yields. This methodology offers an excellent way to synthesize intermediates to be used in drug synthesis. Inline separation allows the collection of pure products and their immediate consumption in the following steps. Overall isolated yields for cinnarizine, cyclizine, and a buclizine derivative are 82, 94, and 87 %, respectively. The total residence time for the four steps is 90 min with a productivity of 2 mmol h-1. The incredible bulk: Bulk alcohols are converted continuously into chlorides using HCl in a microflow. A reaction network that consists of four steps and two inline separations leads to the continuous preparation of cinnarizine, cyclizine, and a buclizine derivative with yields of 82, 94, and 87 %, respectively. The total residence time for the four steps is 90 min with a productivity of 2 mmol h-1.
- Borukhova, Svetlana,Nol, Timothy,Hessel, Volker
-
-
- Catalytic oxidation of alkanes by a (salen)osmium(VI) nitrido complex using H2O2 as the terminal oxidant
-
The osmium(vi) nitrido complex, [OsVI(N)(L)(CH3OH)]+ (1, L = N,N′-bis(salicylidene)-o-cyclohexyldiamine dianion) is an efficient catalyst for the oxidation of alkanes under ambient conditions using H2O2 as the oxidant. Alkanes are oxidized to the corresponding alcohols and ketones, with yields up to 75% and turnover numbers up to 2230. Experimental and computational studies are consistent with a mechanism that involves O-atom transfer from H2O2 to [OsVI(N)(L)]+ to generate an [OsVIII(N)(O)(L)]+ active intermediate.
- Chen, Man,Pan, Yi,Kwong, Hoi-Ki,Zeng, Raymond J.,Lau, Kai-Chung,Lau, Tai-Chu
-
supporting information
p. 13686 - 13689
(2015/09/02)
-
- Photoinduced, Copper-Catalyzed Carbon-Carbon Bond Formation with Alkyl Electrophiles: Cyanation of Unactivated Secondary Alkyl Chlorides at Room Temperature
-
We have recently reported that, in the presence of light and a copper catalyst, nitrogen nucleophiles such as carbazoles and primary amides undergo C-N coupling with alkyl halides under mild conditions. In the present study, we establish that photoinduced, copper-catalyzed alkylation can also be applied to C-C bond formation, specifically, that the cyanation of unactivated secondary alkyl chlorides can be achieved at room temperature to afford nitriles, an important class of target molecules. Thus, in the presence of an inexpensive copper catalyst (CuI; no ligand coadditive) and a readily available light source (UVC compact fluorescent light bulb), a wide array of alkyl halides undergo cyanation in good yield. Our initial mechanistic studies are consistent with the hypothesis that an excited state of [Cu(CN)2]- may play a role, via single electron transfer, in this process. This investigation provides a rare example of a transition metal-catalyzed cyanation of an alkyl halide, as well as the first illustrations of photoinduced, copper-catalyzed alkylation with either a carbon nucleophile or a secondary alkyl chloride.
- Ratani, Tanvi S.,Bachman, Shoshana,Fu, Gregory C.,Peters, Jonas C.
-
supporting information
p. 13902 - 13907
(2016/01/15)
-
- The continuous reaction device and method of using the continuous composite (by machine translation)
-
PROBLEM TO BE SOLVED: compounds with high productivity can be generated. SOLUTION: 1 the raw material supply section 12 and a first, a second and 2 the raw material supply section 14, and a reaction part 18, the first reaction part 1 from the raw material supply section 1 and a second quantity of raw material, the raw material supply section 2 from the first reaction part 2 and a second quantity of raw material, the raw material supply section 1 from the first reaction part 1 and a second temperature of the raw material, the raw material supply section 2 from the first reaction part 2 and supplied to the temperature of the raw material, and having a control part 22, a continuous reaction device as shown in the drawing. Selected drawing: fig. 1 (by machine translation)
- -
-
Paragraph 0180
(2017/01/02)
-
- Spectroscopic Analyses on Reaction Intermediates Formed during Chlorination of Alkanes with NaOCl Catalyzed by a Nickel Complex
-
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
-
p. 10656 - 10666
(2015/11/27)
-
- Light-triggered oxy-chlorination of cyclohexane by metal chlorides
-
This paper discloses that visible light can trigger efficiently the oxy-chlorination of cyclohexane by some metal chlorides at ambient temperature under N2 atmosphere. Among the metal chlorides examined, only a few metal chlorides with easily changeable valence such as VOCl3, CuCl2·2H2O and FeCl3·6H 2O were found to be efficient chlorinating agents for this photoreaction in acetonitrile or acetone, providing mono- and di-chlorinated cyclohexane as main products, with concomitant formation of a small amount of cyclohexene, cyclohexanol and cyclohexanone. CuCl2·2H 2O was the most active chlorinating agent for this photoreaction, but provided an appreciable amount of the non-chlorinated products. FeCl 3·6H2O possessed the best selectivity for the chlorinated products. In addition, it was found that a suitable amount of concentrated HCl was capable of realizing the visible light-driven CuCl 2·2H2O or the UV-driven FeCl3· 6H2O to catalyze photo-oxy-chlorination of cyclohexane under air, providing a high chlorination efficiency (turnover number (TON), 2.46 for CuCl2·2H2O and 4.66 for FeCl3· 6H2O). This is likely because the HCl can itself be used as a chlorinating agent; on the other hand, it also efficiently promotes the photoredox cycling of CuCl2 or FeCl3, as supported by UV-vis spectra. Based on these findings, a free radical mechanism for the present photo-oxy-chlorination system was proposed.
- Wu, Wenfeng,Fu, Zaihui,Wen, Xu,Wang, Yongjun,Zou, Shuai,Meng, Yue,Liu, Yachun,Kirk, Steven Robert,Yin, Dulin
-
p. 483 - 489
(2013/12/04)
-
- Aromatic cation activation: Nucleophilic substitution of alcohols and carboxylic acids
-
A new method for the nucleophilic substitution of alcohols and carboxylic acids using aromatic tropylium cation activation has been developed. This article reports the use of chloro tropylium chloride for the rapid generation of alkyl halides and acyl chlorides under very mild reaction conditions. It demonstrates, for the first time, the synthetic potential of tropylium cations in promoting chemical transformations.
- Nguyen, Thanh V.,Bekensir, Alp
-
supporting information
p. 1720 - 1723
(2014/04/17)
-
- A convenient method for producing mono- and dichlorohydrins from glycerol
-
A new method for the transformation of glycerol into mono- and dichlorohydrins has been studied. With trimethylchlorosilane as chlorinating agent and acetic acid as catalyst, mono- and dichlorohydrins have been obtained in high yields and selectivity. In fact, under different reaction conditions, the synthesis of α-monochlorohydrin (3-chloropropan-1,2-diol) or α,γ-dichlorohydrin (1,3-dichloropropan-2-ol) as predominant product has been achieved. This process was also exploited for the valorisation of the crude mixture of glycerol and monochlorohydrin (glyceric mixture), a by-product from an earlier BioDiesel production. A reaction mechanism has been proposed based on investigations on the chlorination of different alcohols.
- Giomi, Donatella,Malavolti, Marino,Piccolo, Oreste,Salvini, Antonella,Brandi, Alberto
-
p. 46319 - 46326
(2015/02/19)
-
- Stereoretentive chlorination of cyclic alcohols catalyzed by titanium(IV) tetrachloride: Evidence for a front side attack mechanism
-
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.
-
p. 2118 - 2127
(2013/04/10)
-
- DMSO-catalyzed chlorination of alcohols using N-phenylbenzimidoyl chloride
-
N-phenylbenzimidoyl chloride has been demonstrated as an efficient chlorination reagent catalyzed by dimethyl sulfoxide (DMSO) in conversion of alcohols to corresponding chlorides. The reaction conditions were mild, and most of the substrates gave satisfactory yields. The configuration inversion of the chlorination was proved using optically active phenyl alcohols. The amount of DMSO can be as low as 0.001 eq without reducing the efficiency of the chlorination. A plausible mechanism for the reaction was proposed and proved by experiments. The reaction is stereoselective and potentially chemoselective among primary benzyl alcohols, secondary benzyl alcohols, and unactivated aliphatic alcohols.
- Wang, Qiang,Xu, Jian,Xu, Zhou-Qing,Yan, Ji-Dan
-
p. 2071 - 2076
(2013/06/05)
-
- Chlorination of hydrocarbons with CCl4 catalyzed by complexes of Mn, Mo, V, Fe
-
Catalytic chlorination of alkanes, cycloalkanes, and adamantane utilizing tetrachloromethane as the source of chlorine and applying catalysts containing manganese, molybdenum, vanadium, and iron activated with nitrile ligands, alcohols, and water was fulfilled. The optimum ratios of catalysts and reagents and the best reaction conditions were found for selective synthesis of chlorine-substituted hydrocarbons derivatives. Pleiades Publishing, Ltd., 2013.
- Khusnutdinov,Shchadneva,Bayguzina,Oshnyakova,Mayakova,Dzhemilev
-
p. 1557 - 1566
(2014/02/14)
-
- C-HALOGEN BOND FORMATION
-
Methods of halogenating a carbon containing compound having an sp3 C-H bond are provided. Methods of fluorinating a carbon containing compound comprising halogenation with Cl or Br followed by nucleophilic substitution with F are provided. Methods of direct oxidative C-H fluorination of a carbon containing compound having an sp3 C-H bond are provided. The halogenated products of the methods are provided.
- -
-
Paragraph 0111-0118
(2013/03/26)
-
- Hydration of alkenes and cycloalkenes in the presence of chromium and copper complexes
-
Chromium and copper complexes catalyzed hydration of acyclic and cyclic olefins in the presence of carbon tetrachloride at 110-160 C (4-12 h) with formation of the corresponding alcohols.
- Khusnutdinov,Oshnyakova,Shchadneva
-
p. 1428 - 1432
(2014/01/06)
-
- Introducing copper as catalyst for oxidative alkane dehydrogenation
-
The dehydrogenation of n-hexane and cycloalkanes giving n-hexene and cycloalkenes has been observed in the reaction of such hydrocarbons with hydrogen peroxide, in the presence of copper complexes bearing trispyrazolylborate ligands. This catalytic transformation provides the typical oxidation products (alcohol and ketones) with small amounts of the alkenes, a novel feature in this kind of oxidative processes. Experimental data exclude the participation of hydroxyl radicals derived from Fenton-like reaction mechanisms. DFT studies support a copper-oxo active species, which initiates the reaction by H abstraction. Spin crossover from the triplet to the singlet state, which is required to recover the catalyst, yields the major hydroxylation and minor dehydrogenation products. Further calculations suggested that the superoxo and hydroperoxo species are less reactive than the oxo. A complete mechanistic proposal in agreement with all experimental and computational data is proposed.
- Conde, Ana,Vilella, Laia,Balcells, David,Díaz-Requejo, M. Mar,Lledós, Agustí,Pérez, Pedro J.
-
p. 3887 - 3896
(2013/04/23)
-
- Metal chlorides-catalyzed selective oxidation of cyclohexane by molecular oxygen under visible light irradiation
-
The development of mild and efficient process for the selective oxidation of organic compounds with molecular oxygen can be one of the key technologies for synthesizing oxygenates. Here, a visible light-driven metal chloride to catalyze the selective oxidation of cyclohexane was carried out at ambient temperature under a pure O2 atmosphere. Among the metal salts examined, only a few metal chlorides, with easily changeable valence, such as CuCl2·2H2O, VOCl3, and FeCl 3·6H2O, were found to be active to this photo-oxidation reaction in acetonitrile or acetone, providing cyclohexanol, cyclohexanone, chlorocyclohexane, and cyclohexene as main products. This is likely because the weak coordination of these metal chlorides with solvent molecules plays key roles in absorbing visible light and realizing photoredox cycle, as supported by UV-Vis spectrum and cyclic voltammetry measurements. Among these active metal chlorides, CuCl2·2H2O showed a higher conversion and better selectivity for cyclohexanol and cyclohexanone (the oxygenated products) than the other two metal chlorides, and its activity and selectivity for chlorocyclohexane were significantly improved in the case of adding concentrated HCl, because HCl promotes the photocatalytic cycling, as supported by UV-Vis spectra. Notably, a high turnover frequency (TOF, 7.4 h-1) and an excellent selectivity for the oxygenated products (93%) were achieved upon a low concentration of CuCl 2·2H2O (0.002 mol L-1), 0.1 ml of concentrated HCl and 2 atm of O2 pressure. Based on these findings, a free radical mechanism for the present photocatalysis system was proposed.
- Wu, Wenfeng,He, Xiangling,Fu, Zaihui,Liu, Yachun,Wang, Yanlong,Gong, Xinglang,Deng, Xiaolin,Wu, Haitao,Zou, Yanhong,Yu, Ningya,Yin, Dulin
-
scheme or table
p. 6 - 12
(2012/03/11)
-
- Iron(III)-catalyzed halogenations by substitution of sulfonate esters
-
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
-
p. 963 - 972
(2011/06/20)
-
