Benzylic Mono Research Articles

Persulfate-promoted benzylic mono- and difluorination: A mechanistic study

A systematic investigation has been conducted into the mechanism for the persulfate-promoted benzylic mono- and difluorination with Selectfluor by using density functional theory (DFT). In the monofluorination, the role of SO4− (from the substrate-assisted cleavage of S2O82− in the initiation phase) is just to trigger fluorination by producing the initial benzyl radical. The cationic N-radical from the fluorine transfer between the benzyl radical and Selectfluor can abstract hydrogen from the substrate, generating the benzyl radical to complete the reaction cycle. The difluorination contains the monofluorination and the second fluorine transfer. The benzylic CH activation in the monofluorination product can be achieved by cationic N-radical or SO4−. Whether in monofluorination or in difluorination, the rate-determining step is the generation of SO4−.

ChemInform Abstract: Transition‐Metal‐Free C—H Oxidative Activation: Persulfate‐Promoted Selective Benzylic Mono‐ and Difluorination.

ChemInformVolume 46, Issue 28 Preparative Organic Chemistry ChemInform Abstract: Transition-Metal-Free C—H Oxidative Activation: Persulfate-Promoted Selective Benzylic Mono- and Difluorination. Jing-jing Ma, Jing-jing Ma Nanjing Univ. Sci. Technol., Nanjing 210094, Peop. Rep. ChinaSearch for more papers by this authorWen-bin Yi, Wen-bin Yi Nanjing Univ. Sci. Technol., Nanjing 210094, Peop. Rep. ChinaSearch for more papers by this authorGuo-ping Lu, Guo-ping Lu Nanjing Univ. Sci. Technol., Nanjing 210094, Peop. Rep. ChinaSearch for more papers by this authorChun Cai, Chun Cai Nanjing Univ. Sci. Technol., Nanjing 210094, Peop. Rep. ChinaSearch for more papers by this author Jing-jing Ma, Jing-jing Ma Nanjing Univ. Sci. Technol., Nanjing 210094, Peop. Rep. ChinaSearch for more papers by this authorWen-bin Yi, Wen-bin Yi Nanjing Univ. Sci. Technol., Nanjing 210094, Peop. Rep. ChinaSearch for more papers by this authorGuo-ping Lu, Guo-ping Lu Nanjing Univ. Sci. Technol., Nanjing 210094, Peop. Rep. ChinaSearch for more papers by this authorChun Cai, Chun Cai Nanjing Univ. Sci. Technol., Nanjing 210094, Peop. Rep. ChinaSearch for more papers by this author First published: 25 June 2015 https://doi.org/10.1002/chin.201528039Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume46, Issue28July, 2015 RelatedInformation

Transition-metal-free C-H oxidative activation: persulfate-promoted selective benzylic mono- and difluorination.

An operationally simple and selective method for the direct conversion of benzylic C-H to C-F to obtain mono- and difluoromethylated arenes using Selectfluor™ as a fluorine source is developed. Persulfate can be used to selectively activate benzylic hydrogen atoms toward C-F bond formation without the aid of transition metal catalysts.

A theoretical study of the bowl-to-bowl inversion of sumanene derivatives

A theoretical study was conducted on the bowl-to-bowl inversion of sumanene: its benzylic mono-, di-, and trianion species and its mono-, di-, and trinaphthosumanenes. The use of B3LYP/6-311+G(2d,p) for the B3LYP/6-31G(d,p)-optimized geometries approximately reproduced the experimental values for the bowl-to-bowl inversion of sumanene, and its benzylic mono- and dianion species. The value for the trianion was estimated to be around 21 kcal/mol using the above levels. The investigation of naphthosumanenes clearly indicated a noted increase in the inversion barrier with additional fused rings. The calculated inversion barrier for mononaphthosumanene also correctly reproduced the experimental value (32.2 kcal/mol) using the above levels (31.4 kcal/mol). The calculated barrier for trinaphthosumanene reached 63.8 kcal/mol, therefore, the bowl-to-bowl inversion is less likely to occur under realistic conditions.

Quantitative Production of Compound I from a Cytochrome P450 Enzyme at Low Temperatures. Kinetics, Activation Parameters, and Kinetic Isotope Effects for Oxidation of Benzyl Alcohol

Cytochrome P450 enzymes are commonly thought to oxidize substrates via an iron(IV)-oxo porphyrin radical cation transient termed Compound I, but kinetic studies of P450 Compounds I are essentially nonexistent. We report production of Compound I from cytochrome P450 119 (CYP119) in high conversion from the corresponding Compound II species at low temperatures in buffer mixtures containing 50% glycerol by photolysis with 365 nm light from a pulsed lamp. Compound I was studied as a reagent in oxidations of benzyl alcohol and its benzylic mono- and dideuterio isotopomers. Pseudo-first-order rate constants obtained at -50 degrees C with concentrations of substrates between 1.0 and 6.0 mM displayed saturation kinetics that gave binding constants for the substrate in the Compound I species (K(bind)) and first-order rate constants for the oxidation reactions (k(ox)). Representative results are K(bind) = 214 M(-1) and k(ox) = 0.48 s(-1) for oxidation of benzyl alcohol. For the dideuterated substrate C(6)H(5)CD(2)OH, kinetics were studied between -50 and -25 degrees C, and a van't Hoff plot for complexation and an Arrhenius plot for the oxidation reaction were constructed. The H/D kinetic isotope effects (KIEs) at -50 degrees C were resolved into a large primary KIE (P = 11.9) and a small, inverse secondary KIE (S = 0.96). Comparison of values extrapolated to 22 degrees C of both the rate constant for oxidation of C(6)H(5)CD(2)OH and the KIE for the nondeuterated and dideuterated substrates to values obtained previously in laser flash photolysis experiments suggested that tunneling could be a significant component of the total rate constant at -50 degrees C.

Bowl-to-bowl inversion of sumanene derivatives

The bowl-to-bowl inversion of the non-planar bowl-shaped compounds derived from sumanene as a fullerene C3v fragment was found to be slow and tuned by a solvent, and the benzylic mono- and di-anions inverted even more slowly.

A Simple Key for Benzylic Mono- and gem-Dibromination of Primary Aromatic Amine Derivatives Using Molecular Bromine

Quantitative benzylic mono- and gem-dibromination on primary aromatic amine derivatives have been achieved using molecular bromine and by protecting the amino group as a succinimide moiety. The reactions of N-(o/m/p-tolyl)succinimides 5a-c with 1.25 equivalents of molecular bromine in CCl4 at room temperature furnished the corresponding benzylic monobrominated products 6a-c in 92-94% yields, while with 2.5 equivalents of molecular bromine in refluxing CCl4 gem-dibromo products 7a-c were obtained in 94-96% yields. It is also possible to carry out nuclear bromination in these N-protected primary aromatic amines at an alternate site by using suitably substituted aniline derivatives. Thus the reaction of 3 with 1.25 equivalents of molecular bromine in acetic acid gave the desired monobrominated product 4 in nearly 100% yield.

Side Chain Bromination of Mono and Dimethyl Heteroaromatic and Aromatic Compounds by Solid Phase N-Bromosuccinimide Reaction without Radical Initiator under Microwave

Abstract A series of side chain mono and dibromo derivatives of mono and dimethyl heteroaromatic and aromatic compounds (1–17) were synthesized by one step solid phase N-bromosuccinimide (NBS) reaction without radical initiator by microwave irradiation. The benzylic mono and dibromo products were exclusively preferred except in the case of 6-methylpyridine amides (8 and 9) where nuclear and also side chain bromination resulted. Naphthyridine systems resulted improved yields. By this method, we also report the synthesis of 2-pivaloylaminopterin-6-carbaldehyde.

Phosphane and Bis(phosphane) Ligands from Phosphinic Acids

The Boyd−Regan methodology allowed for access to various cyclic or benzylic mono- and bis(phosphinic acids) 1−6. The reduction of monophosphinic acids to secondary phosphanes 7−9 was achieved with silanes. On the other hand, reduction of the bis(phosphinic acids) with LiAlH4 led to bis(phosphanes) 12−13. Various cyclic phosphanes and bis(phosphanes) were obtained by the alkylation of these secondary phosphanes (as their borane adducts). The Michael addition of the same borane adducts to vinylic phosphonates led to phosphane−phosphonates which could be hydrolysed to new hydrosoluble phosphanes.

Phosphane and Bis(phosphane) Ligands from Phosphinic Acids

The Boyd−Regan methodology allowed for access to various cyclic or benzylic mono- and bis(phosphinic acids) 1−6. The reduction of monophosphinic acids to secondary phosphanes 7−9 was achieved with silanes. On the other hand, reduction of the bis(phosphinic acids) with LiAlH4 led to bis(phosphanes) 12−13. Various cyclic phosphanes and bis(phosphanes) were obtained by the alkylation of these secondary phosphanes (as their borane adducts). The Michael addition of the same borane adducts to vinylic phosphonates led to phosphane−phosphonates which could be hydrolysed to new hydrosoluble phosphanes.

Bioactivation of benzylic and allylic alcohols via sulfo-conjugation

Although sulfo-conjugation, in general, has been regarded as a detoxification process in the xenobiotic metabolism, there is a substantial body of data supporting that the same reaction can also lead to activation of certain types of chemical carcinogens and mutagens. Examples include some aromatic amines and amides, alkenylbenzenes, methyl-substituted polyaromatic hydrocarbons, nitrotoluenes and nitrosamines. The N- or O-hydroxy derivatives of these compounds undergo sulfonation to form extremely reactive sulfuric acid esters that can play a role as ultimate carcinogenic/mutagenic metabolites. Previous studies from several laboratories have shown that hydroxymethyl polyarenes, such as hydroxymethylbenz[ a]anthracenes, 6-hydroxymethylbenzo[ a]pyrene, and 1-hydroxymethylpyrene, are activated to reactive benzylic sulfuric acid esters, preferentially by rat hepatic hydroxysteroid sulfotransferase. Some aromatic hydrocarbons bearing the secondary benzylic hydroxy functionality can also yield electrophilic sulfate esters in the presence of hepatic sulfotransferase activity. Thus, benzylic mono- and dihydroxy derivatives of cyclopenta[ cd]pyrene form mutagenic and DNA binding species when incubated with rat liver cytosol and the sulfo-group donor, 3′-phosphoadenosine-5′-phosphosulfate. 1-Hydroxy-3-methylcholanthrene that also possesses the cyclopenta-fused ring system appears to be metabolically activated through sulfo-conjugation. Likewise, benzo[ a]pyrene tetraol might be activated through sulfuric acid esterification at one of two benzylic hydroxyl groups. Methylene-bridged polyarenols represent another potential group of cyclic secondary benzylic alcohols that can be activated by sulfotransferases. Certain non-polycyclic aromatic type benzylic alcohols have also been proposed to undergo sulfotransferase-mediated activation. Besides benzylic sulfonation, sulfuric acid esterification of certain allylic alcohols can produce reactive species.

Preparation, 13C NMR/DFT/IGLO Study of Benzylic Mono- and Dications, and Attempted Preparation of a Trication1

Substituted benzylic mono- and dications were prepared and investigated by 1H and 13C NMR spectroscopy and DFT/IGLO calculations. Combined experimental and theoretical study suggest that the struct...

Synthesis of benzylic mono(α,α-difluoromethylphosphonates) and benzylic bis(α,α-difluoromethylphosphonates) via electrophilic fluorination

A series of benzylic mono(α,α-difluoromethylphosphonates) and benzylic bis(α,α-difluoromethylphosphonates) have been prepared via electrophilic fluorination of the corresponding benzylic phosphonates.

Consecutive Cyclometalation by Platinum(II)

The mechanism of the selective formation of the new benzylic mono- and bicyclometalated platinum(II) complexes 2a,b and 3b has been studied. Monitoring the initial sp3 C−H activation of the ligand DIPPIDH (α2-(diisopropylphosphino)isodurene; 1) and (1,5-cyclooctadiene)dimethylplatinum(II) ((COD)PtMe2) at room temperature by 31P{1H} NMR reveals that, after displacement of 1,5-cyclooctadiene, the complex cis-(DIPPIDH)(DIPPID)PtMe (2a) is formed selectively by oxidative addition of a benzylic C−H bond and subsequent reductive elimination of CH4. This reaction is controlled by electronic factors. Heating of 2a results in isomerization to the thermodynamically more stable isomer trans-(DIPPIDH)(DIPPID)PtMe (2b) as well as the formation of the double-C−H activated complex trans-(DIPPID)2Pt (3b) with liberation of CH4 in parallel pathways. Continuous heating results in the quantitative formation of the thermally stable 3b. Mechanistically, the second C−H activation proceeds analogously to the first one. The mole...

ChemInform Abstract: Single and Double Reductive Cleavage of C‐O Bonds of Aromatic Dimethyl Acetals and Ketals: Generation of Benzylic Mono‐ and Dicarbanions.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Single and double reductive cleavage of CO bonds of aromatic dimethyl acetals and ketals: Generation of benzylic mono- and dicarbanions

The reductive cleavage of aromatic dimethyl acetals and ketals, 1, with Li metal in THF at low temperature allows the generation of stable α-alkoxy-α-arylsubstituted carbanions, avoiding the Wittig rearrangement. Reaction of these carbanions with various electrophiles afforded the expected products 2. Further in situ reaction of compounds 2 afforded the products of reductive electrophilic disubstitution, 3.

ChemInform Abstract: Reductive Coupling by Chromium(0) ‐ (Bibenzyl)‐ and (Stilbene)tricarbonylchromium(0) Complexes by a One‐Pot Reaction from Benzylic Halides.

AbstractReaction of benzylic mono‐ and dihalides such as (I) or (III) with Cr(CO)3(NH3)3 leads to diarylethanes and ‐ethenes such as (II) or (IV) in satisfactory yields.

Reductive Coupling by Chromium(0) – (Bibenzyl)‐ and (Stilbene)tricarbonylchromium(0) Complexes by a One‐Pot Reaction from Benzylic Halides

Reaction of Cr(CO)3(NH3)3 with benzylic mono-, di-, and trihalides leads to the formation of 1,2-diarylethanes, -ethenes, and diphenylethyne in satisfactory yields. Di(halomethyl)benzene derivatives yield product mixtures containing both reduction products and coupling products. With a higher excess in chromium(O), under otherwise unchanged reaction conditions, the corresponding (arene)tricarbonylchromium(O) complexes of the coupling products are formed in a one-pot reaction from the benzylic halides.

Highly reactive metallic nickel: reductive homocoupling reagent for benzylic mono- and polyhalides

Metallic nickel, prepared by the reduction of nickel halides with lithium in glyme using naphthalene as an electron carrier, was found to be a useful reagent for the homocoupling of benzylic mono- and polyhalides. Benzyl halides reacted with metallic nickel at room temperature to give the corresponding 1,2-diarylethanes in good to high yields and functional groups on the aromatic ring such as methoxy, chloro, bromo, nitro, cyano, and alkoxycarbonyl groups were not affected under the conditions employed. Benzylic monohalides (1-chloromethyl)- or 2-(bromomethyl)naphthalene, chlorodiphylmethane, and 9-bromofluorene) also underwent coupling reactions with metallic nickel at room temperature to give the corresponding ethane derivatives. On the other hand, benzylic di- and trihalides such as ..cap alpha..,..cap alpha..-dibromotoluene and ..cap alpha..,..cap alpha..,..cap alpha..-trichlorotoluene yielded mixtures of cis and trans isomers of substituted ethenes. The intermediate of the reaction, benzylnickel complex, was trapped with electron deficient olefins such as methyl acrylate and acrylonitrile. 52 references, 2 tables.