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relating to benzyl
the univalent radical derived from toluene (同)benzyl_group, benzyl radical

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/10/10 13:51:35」(JST)

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Not to be confused with benzil, benzoyl, or phenyl.

The structure of the benzyl group

In organic chemistry, benzyl is the substituent or molecular fragment possessing the structure C₆H₅CH₂-. Benzyl features a benzene ring attached to a CH₂ group.^[1]

Nomenclature[edit]

In IUPAC nomenclature the prefix benzyl refers to a C₆H₅CH₂ substituent, for example benzyl chloride or benzyl benzoate. Benzyl is not to be confused with phenyl with the formula C₆H₅. The term benzylic is used to describe the position of the first carbon covalently bonded adjacent to a benzene or other aromatic ring. For example a positive charge, which is stabilized in this position, is referred to as a "benzylic" carbocation. The benzyl free radical has the formula C₆H₅CH₂. The benzyl carbocation has the formula C₆H₅CH₂⁺; the carbanion has the formula C₆H₅CH₂^-. None of these species can be formed in significant amounts under normal conditions, but they are useful referents for discussion of mechanisms.

Abbreviations[edit]

The abbreviation "Bn" is frequently used to denote benzyl groups in nomenclature and structural depictions of chemical compounds. For example, benzyl alcohol can be represented as BnOH. This abbreviation is not to be confused with "Bz", which is the abbreviation for the benzoyl group C₆H₅C(O)-, or the phenyl group C₆H₅, abbreviated "Ph".

Reactivity of benzylic centers[edit]

Benzylic positions are endowed with special reactivity, as in oxidation, free radical halogenation, or hydrogenolysis. As a practical example, in the presence of suitable catalysts, p-xylene oxidizes exclusively at the benzylic positions to give terephthalic acid:

CH₃C₆H₄CH₃ + 3 O₂ → HO₂CC₆H₄CO₂H + 2 H₂O

Millions of tonnes of terephthalic acid are produced annually by this method.^[2]

The enhanced reactivity of benzylic positions is attributed to the low bond dissociation energy for benzylic C-H bonds. Specifically, the bond C₆H₅CH₂-H is about 10-15% weaker than other kinds of C-H bonds. The neighboring aromatic ring stabilizes benzyl radicals.

Benzyl protective groups[edit]

Benzyl groups are frequently used in organic synthesis as protective group for alcohols and carboxylic acids.

Two common methods for benzyl ether protection:

reaction of alcohol with benzyl bromide and a strong base such as sodium hydride as in a Williamson ether synthesis^[3]^{[dead link]}
reaction of alcohol with an imidate such as benzyl trichloroacetimidate (C₆H₅CH₂OC(CCl₃)=NH) promoted by trifluoromethanesulfonic acid. An example forming a p-methoxybenzyl (PMB) ether in total synthesis:^[4]

The benzyl group can be removed by hydrogenation. PMB ethers can be cleaved by magnesium bromide –dimethyl sulfide, CAN or DDQ.^[5]

One study ^[6] employs a benzyloxy pyridinium salt as a benzyl transfer reagent for alcohols:

Trifluorotoluene was used as the solvent in the presence of magnesium oxide as an acid scavenger. The reaction type for this conversion is believed to be S_N1 based on the detection of trace amounts of Friedel-Crafts reaction side-products with toluene as a solvent.

References[edit]

^ Carey, F. A., and Sundberg, R. J.; Advanced Organic Chemistry, Part A: Structure and Mechanisms, 5th ed.; Springer: New York, NY, 2008. pp 806–808, 312–313.
^ Richard J. Sheehan, "Terephthalic Acid, Dimethyl Terephthalate, and Isophthalic Acid" in Ullmann's Encyclopedia of Industrial Chemistry, Wiley-VCH, Weinheim, 2002. doi:10.1002/14356007.a26_193
^ DeSelms, R. H.; Benzyl Phenyl Ether Compounds; Enigen Science Publishing: Washington, DC, 2008.
^ Total synthesis of rutamycin B via Suzuki macrocyclization James D. White, Thomas Tiller, Yoshihiro Ohba, Warren J. Porter, Randy W. Jackson, Shan Wang, and Roger Hanselmann 80 Chem. Commun., 1998 doi:10.1039/a707251a
^ Protecting groups Krzysztof Jarowicki and Philip Kocienski J. Chem. Soc., Perkin Trans. 1, 1998, 4005–4037 4005 doi:10.1039/a803688h
^ K. W. C. Poon and G. B. Dudley (2006). "Mix-and-Heat Benzylation of Alcohols Using a Bench-Stable Pyridinium Salt". J. Org. Chem. 71 (10): 3923–3927. doi:10.1021/jo0602773. PMID 16674068.

English Journal

Oxidant controlled Pd-catalysed selective oxidation of primary alcohols.

Liu C, Tang S, Lei A.SourceCollege of Chemistry and Molecular Sciences, Wuhan University, Wuhan, 430072, P. R. China. aiwenlei@whu.edu.cn.
Chemical communications (Cambridge, England).Chem Commun (Camb).2013 Feb 14;49(13):1324-6. doi: 10.1039/c2cc38086b. Epub 2013 Jan 10.
The oxidant controlled palladium catalysed selective oxidation of primary alcohols to aldehydes or esters was investigated. The electronic properties of the benzylic alcohols and the structure of the oxidant are both important factors in controlling the selectivity between aldehydes and esters. A co
PMID 23303167

Nevirapine Bioactivation and Covalent Binding in the Skin.

Sharma AM, Klarskov K, Uetrecht J.AbstractNevirapine (NVP) treatment is associated with serious skin rashes that appear to be immune-mediated. We previously developed a rat model of this skin rash that is immune-mediated and very similar to the rash in humans. Treatment of rats with the major NVP metabolite, 12-OH-NVP, also caused the rash. Most idiosyncratic drug reactions are caused by reactive metabolites; 12-OH-NVP forms a benzylic sulfate, which was detected in the blood of animals treated with NVP or 12-OH-NVP. This sulfate is presumably formed in the liver; however, the skin also has significant sulfotransferase activity. In this study, we used a serum against NVP to detect covalent binding in the skin of rats. There was a large artifact band in immunoblots of whole skin homogenates that interfered with detection of covalent binding; however, when skin was separated into dermal and epidermal fractions, covalent binding was clearly present in the epidermis, which is also the location of sulfotransferases. In contrast to rats, treatment of mice with NVP did not result in covalent binding in the skin or skin rash. Although the reaction of 12-OH-NVP sulfate with nucleophiles such as glutathione is slow, incubation of this sulfate with homogenized human and rat skin led to extensive covalent binding. Incubations of 12-OH-NVP with the soluble fraction from a 9,000xg centrifugation (S9) of rat or human skin homogenate in the presence of 3'-phosphoadenosine-5'-phosphosulfate (PAPS) produced extensive covalent binding, but no covalent binding was detected with mouse skin S9, which suggests that the reason mice do not develop a rash is that they lack the required sulfotransferase. This is the first study to report covalent binding of NVP to rat and human skin. These data provide strong evidence that covalent binding of NVP in the skin is due to 12-OH-NVP sulfate, which is likely responsible for NVP-induced skin rash. Sulfation may represent a bioactivation pathway for other drugs that cause a skin rash.
Chemical research in toxicology.Chem Res Toxicol.2013 Feb 6. [Epub ahead of print]
Nevirapine (NVP) treatment is associated with serious skin rashes that appear to be immune-mediated. We previously developed a rat model of this skin rash that is immune-mediated and very similar to the rash in humans. Treatment of rats with the major NVP metabolite, 12-OH-NVP, also caused the rash.
PMID 23387501

Synthetic studies on pseudo-dimeric lycopodium alkaloids: total synthesis of complanadine b.

Newton JN, Fischer DF, Sarpong R.SourceDepartment of Chemistry, University of California, Berkeley, Berkeley, CA 94720 (USA).
Angewandte Chemie (International ed. in English).Angew Chem Int Ed Engl.2013 Feb 4;52(6):1726-30. doi: 10.1002/anie.201208571. Epub 2013 Jan 10.
Two approaches to the total synthesis of the dimeric Lycopodium alkaloid complanadine B have been achieved. In the first approach (see scheme; route 1), a keto lycodine unit is coupled to another lycodine unit whereas in the latter approach (route 2), selective oxygenation of one of two pseudo-ben
PMID 23307758

Japanese Journal

Formation and characterization of a reactive chromium(V)–oxo complex: mechanistic insight into hydrogen-atom transfer reactions

Kotani Hiroaki,Kaida Suzue,Ishizuka Tomoya,Sakaguchi Miyuki,Ogura Takashi,Shiota Yoshihito,Yoshizawa Kazunari,Kojima Takahiko
Chemical science 6(2), 945-955, 2015-02
… One-step UV-vis spectral changes were observed in the course of the oxidation reactions of BA derivatives by 1 and a kinetic isotope effect (KIE) was observed in the oxidation reactions for deuterated BA derivatives at the benzylic position as substrates. …
NAID 120005555645

Enantioselective Addition of Diethylzinc to Aldehydes Catalyzed by Diastereomeric 1,4-Amino Alcohols with o-Xylylene Skeleton

, , , , ,
Chemistry Letters advpub(0), 2015
… The stereochemical outcome of the reactions was controlled solely by the absolute configuration of the benzylic carbon bearing amino group, and both enantiomers of 1-substituted propanol were obtained with up to 98% (S) and 96% (R) enantiomeric excesses. …
NAID 130004868412

Enantioselective Addition of Diethylzinc to Aldehydes Catalyzed by Diastereomeric 1,4-Amino Alcohols with o-Xylylene Skeleton

, , , , ,
Chemistry Letters 44(3), 345-347, 2015
… The stereochemical outcome of the reactions was controlled solely by the absolute configuration of the benzylic carbon bearing amino group, and both enantiomers of 1-substituted propanol were obtained with up to 98% (S) and 96% (R) enantiomeric excesses. …
NAID 130004868411