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In
organic chemistry Organic chemistry is a subdiscipline within chemistry involving the scientific study of the structure, properties, and reactions of organic compounds and organic materials, i.e., matter in its various forms that contain carbon atoms.Clayden, J ...
, benzyl is the
substituent A substituent is one or a group of atoms that replaces (one or more) atoms, thereby becoming a moiety in the resultant (new) molecule. (In organic chemistry and biochemistry, the terms ''substituent'' and ''functional group'', as well as '' side ...
or molecular fragment possessing the structure . Benzyl features a
benzene Benzene is an organic chemical compound with the molecular formula C6H6. The benzene molecule is composed of six carbon atoms joined in a planar ring with one hydrogen atom attached to each. Because it contains only carbon and hydrogen atoms ...
ring () attached to a
methylene group In organic chemistry, a methylene group is any part of a molecule that consists of two hydrogen atoms bound to a carbon atom, which is connected to the remainder of the molecule by two single bonds. The group may be represented as , where th ...
() group.


Nomenclature

In
IUPAC nomenclature A chemical nomenclature is a set of rules to generate systematic names for chemical compounds. The nomenclature used most frequently worldwide is the one created and developed by the International Union of Pure and Applied Chemistry (IUPAC). Th ...
, the prefix benzyl refers to a substituent, for example
benzyl chloride Benzyl chloride, or α-chlorotoluene, is an organic compound with the formula C6H5CH2Cl. This colorless liquid is a reactive organochlorine compound that is a widely used chemical building block. Preparation Benzyl chloride is prepared in ...
or
benzyl benzoate Benzyl benzoate is an organic compound which is used as a medication and insect repellent. As a medication it is used to treat scabies and lice. For scabies either permethrin or malathion is typically preferred. It is applied to the skin as a ...
. Benzyl is not to be confused with phenyl with the formula . The term benzylic is used to describe the position of the first carbon bonded to a benzene or other
aromatic In chemistry, aromaticity is a chemical property of cyclic ( ring-shaped), ''typically'' planar (flat) molecular structures with pi bonds in resonance (those containing delocalized electrons) that gives increased stability compared to satur ...
ring. For example, is referred to as a "benzylic" carbocation. The benzyl free radical has the formula . The benzyl cation or phenylcarbenium ion is the
carbocation A carbocation is an ion with a positively charged carbon atom. Among the simplest examples are the methenium , methanium and vinyl cations. Occasionally, carbocations that bear more than one positively charged carbon atom are also encount ...
with formula ; the benzyl anion or phenylmethanide ion is the
carbanion In organic chemistry, a carbanion is an anion in which carbon is trivalent (forms three bonds) and bears a formal negative charge (in at least one significant resonance form). Formally, a carbanion is the conjugate base of a carbon acid: :R3 ...
with the formula . None of these species can be formed in significant amounts in the solution phase under normal conditions, but they are useful referents for discussion of
reaction mechanism In chemistry, a reaction mechanism is the step by step sequence of elementary reactions by which overall chemical change occurs. A chemical mechanism is a theoretical conjecture that tries to describe in detail what takes place at each stage o ...
s and may exist as reactive intermediates.


Abbreviations

The abbreviation "Bn" denotes benzyl. 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 In organic chemistry, benzoyl (, ) is the functional group with the formula C6H5CO-. It can be viewed as benzaldehyde missing one hydrogen. The term "benzoyl" should not be confused with benzyl, which has the formula C6H5CH2. The benzoyl group ...
group , or the phenyl group , abbreviated "Ph". Confusingly, in old literature, "Bz" was also used for benzyl.


Reactivity of benzylic centers

The enhanced reactivity of benzylic positions is attributed to the low bond dissociation energy for benzylic C−H bonds. Specifically, the bond is about 10–15% weaker than other kinds of C−H bonds. The neighboring aromatic ring stabilizes benzyl radicals. The data tabulated below compare benzylic C−H bond to related C−H bond strengths. The weakness of the C−H bond reflects the stability of the benzylic radical. For related reasons, benzylic substituents exhibit enhanced reactivity, as in
oxidation Redox (reduction–oxidation, , ) is a type of chemical reaction in which the oxidation states of substrate change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is the gain of electrons or ...
, free radical halogenation, or hydrogenolysis. As a practical example, in the presence of suitable catalysts, ''p''-
xylene In organic chemistry, xylene or xylol (; IUPAC name: dimethylbenzene) are any of three organic compounds with the formula . They are derived from the substitution of two hydrogen atoms with methyl groups in a benzene ring; which hydrogens are s ...
oxidizes exclusively at the benzylic positions to give
terephthalic acid Terephthalic acid is an organic compound with formula C6H4(CO2H)2. This white solid is a commodity chemical, used principally as a precursor to the polyester PET, used to make clothing and plastic bottles. Several million tonnes are produced an ...
: :CH3C6H4CH3 + 3 O2 -> HO2CC6H4CO2H + 2 H2O Millions of tonnes of terephthalic acid are produced annually by this method.


Functionalization at the benzylic position

In a few cases, these benzylic transformations occur under conditions suitable for lab synthesis. The Wohl-Ziegler reaction will brominate a benzylic C–H bond: (). Any non-tertiary benzylic alkyl group will be oxidized to a carboxyl group by aqueous potassium permanganate () or concentrated nitric acid (): (). Finally, the complex of
chromium trioxide Chromium trioxide (also known as chromium(VI) oxide or chromic anhydride) is an inorganic compound with the formula CrO3. It is the acidic anhydride of chromic acid, and is sometimes marketed under the same name. This compound is a dark-purple s ...
and
3,5-dimethylpyrazole 3,5-Dimethylpyrazole is an organic compound with the formula (CH3C)2CHN2H. It is one of several isomeric derivatives of pyrazole that contain two methyl substituents. The compound is unsymmetrical but the corresponding conjugate acid (pyrazoliu ...
() will selectively oxidize a benzylic methylene group to a carbonyl: (). 2-iodoxybenzoic acid in DMSO performs similarly.


As a protecting group

Benzyl groups are occasionally employed as protecting groups in organic synthesis. Their installation and especially their removal require relatively harsh conditions, so benzyl is not typically preferred for protection.


Alcohol protection

Benzyl is commonly used in organic synthesis as a robust protecting group for
alcohol Alcohol most commonly refers to: * Alcohol (chemistry), an organic compound in which a hydroxyl group is bound to a carbon atom * Alcohol (drug), an intoxicant found in alcoholic drinks Alcohol may also refer to: Chemicals * Ethanol, one of sev ...
s and
carboxylic acid In organic chemistry, a carboxylic acid is an organic acid that contains a carboxyl group () attached to an R-group. The general formula of a carboxylic acid is or , with R referring to the alkyl, alkenyl, aryl, or other group. Carboxyli ...
s. * Treatment of alcohol with a strong base such as powdered
potassium hydroxide Potassium hydroxide is an inorganic compound with the formula K OH, and is commonly called caustic potash. Along with sodium hydroxide (NaOH), KOH is a prototypical strong base. It has many industrial and niche applications, most of which exp ...
or
sodium hydride Sodium hydride is the chemical compound with the empirical formula Na H. This alkali metal hydride is primarily used as a strong yet combustible base in organic synthesis. NaH is a saline (salt-like) hydride, composed of Na+ and H− ions, in ...
and benzyl halide ( BnCl or BnBr) *: * Monobenzylation of
diol A diol is a chemical compound containing two hydroxyl groups ( groups). An aliphatic diol is also called a glycol. This pairing of functional groups is pervasive, and many subcategories have been identified. The most common industrial diol is e ...
s can be achieved using Ag2O in
dimethylformamide Dimethylformamide is an organic compound with the formula ( CH3)2NC(O)H. Commonly abbreviated as DMF (although this initialism is sometimes used for dimethylfuran, or dimethyl fumarate), this colourless liquid is miscible with water and the majo ...
(DMF) at ambient to elevated temperatures * Primary alcohols can be selectively benzylated in presence of phenol functional groups using Cu(acac)2


Deprotection methods

Benzyl ethers can be removed under '' reductive conditions'', ''
oxidative Redox (reduction–oxidation, , ) is a type of chemical reaction in which the oxidation states of substrate change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is the gain of electrons or a ...
conditions'', and the use of ''Lewis Acids''. * Removed using hydrogenolysis *: * Single electron process with Na/ NH3 or Li/NH3 * Benzyl protecting groups can be removed using a wide range of oxidizing agents including: ** CrO3/
acetic acid Acetic acid , systematically named ethanoic acid , is an acidic, colourless liquid and organic compound with the chemical formula (also written as , , or ). Vinegar is at least 4% acetic acid by volume, making acetic acid the main componen ...
at ambient temperature **
Ozone Ozone (), or trioxygen, is an inorganic molecule with the chemical formula . It is a pale blue gas with a distinctively pungent smell. It is an allotrope of oxygen that is much less stable than the diatomic allotrope , breaking down in the l ...
** ''N''-Bromosuccinimide (NBS) ** ''N''-Iodosuccinimide (NIS) *
Trimethylsilyl A trimethylsilyl group (abbreviated TMS) is a functional group in organic chemistry. This group consists of three methyl groups bonded to a silicon atom minus;Si(CH3)3 which is in turn bonded to the rest of a molecule. This structural group is ch ...
iodide (Me3SiI) in
dichloromethane Dichloromethane (DCM or methylene chloride, methylene bichloride) is an organochlorine compound with the formula . This colorless, volatile liquid with a chloroform-like, sweet odour is widely used as a solvent. Although it is not miscible wit ...
at ambient temperature (selectivity can be achieved under specific conditions)


The ''p''-methoxybenzyl protecting group

''p''-Methoxybenzyl (PMB) is used as a
protecting group A protecting group or protective group is introduced into a molecule by chemical modification of a functional group to obtain chemoselectivity in a subsequent chemical reaction. It plays an important role in multistep organic synthesis. In man ...
for
alcohols In chemistry, an alcohol is a type of organic compound that carries at least one hydroxyl () functional group bound to a saturated carbon atom. The term ''alcohol'' originally referred to the primary alcohol ethanol (ethyl alcohol), which is ...
in
organic synthesis Organic synthesis is a special branch of chemical synthesis and is concerned with the intentional construction of organic compounds. Organic molecules are often more complex than inorganic compounds, and their synthesis has developed into one o ...
( 4-Methoxybenzylthiol is used to protect thiols). * Strong base such as powdered
potassium hydroxide Potassium hydroxide is an inorganic compound with the formula K OH, and is commonly called caustic potash. Along with sodium hydroxide (NaOH), KOH is a prototypical strong base. It has many industrial and niche applications, most of which exp ...
or
sodium hydride Sodium hydride is the chemical compound with the empirical formula Na H. This alkali metal hydride is primarily used as a strong yet combustible base in organic synthesis. NaH is a saline (salt-like) hydride, composed of Na+ and H− ions, in ...
and ''p''-methoxybenzyl halide (chloride or bromide) * 4-methoxybenzyl-2,2,2-trichloroacetimidate can be used to install the PMB group in presence of: ** Scandium (III) triflate (Sc(OTf)3) in toluene at 0 °C **
Trifluoromethanesulfonic acid Triflic acid, the short name for trifluoromethanesulfonic acid, TFMS, TFSA, HOTf or TfOH, is a sulfonic acid with the chemical formula CF3SO3H. It is one of the strongest known acids. Triflic acid is mainly used in research as a catalyst for es ...
(TfOH) in
dichloromethane Dichloromethane (DCM or methylene chloride, methylene bichloride) is an organochlorine compound with the formula . This colorless, volatile liquid with a chloroform-like, sweet odour is widely used as a solvent. Although it is not miscible wit ...
at 0 °C **:


Deprotection methods

* 2,3-Dichloro-5,6-dicyano-''p''-benzoquinone (DDQ) *: * Conditions for deprotection of benzyl group are applicable for cleavage of the PMB protecting group


Amine protection

The benzyl group is occasionally used as a
protecting group A protecting group or protective group is introduced into a molecule by chemical modification of a functional group to obtain chemoselectivity in a subsequent chemical reaction. It plays an important role in multistep organic synthesis. In man ...
for
amine In chemistry, amines (, ) are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia (), wherein one or more hydrogen atoms have been replaced by a substituent ...
s in
organic synthesis Organic synthesis is a special branch of chemical synthesis and is concerned with the intentional construction of organic compounds. Organic molecules are often more complex than inorganic compounds, and their synthesis has developed into one o ...
. Other methods exist. * Aqueous potassium carbonate and benzyl halide ( BnCl, BnBr) in
methanol Methanol (also called methyl alcohol and wood spirit, amongst other names) is an organic chemical and the simplest aliphatic alcohol, with the formula C H3 O H (a methyl group linked to a hydroxyl group, often abbreviated as MeOH). It is ...
*: *
Benzaldehyde Benzaldehyde (C6H5CHO) is an organic compound consisting of a benzene ring with a formyl substituent. It is the simplest aromatic aldehyde and one of the most industrially useful. It is a colorless liquid with a characteristic almond-like odor. ...
, 6 M
HCl HCL may refer to: Science and medicine * Hairy cell leukemia, an uncommon and slowly progressing B cell leukemia * Harvard Cyclotron Laboratory, from 1961 to 2002, a proton accelerator used for research and development * Hollow-cathode lamp, a s ...
and NaBH3CN in
methanol Methanol (also called methyl alcohol and wood spirit, amongst other names) is an organic chemical and the simplest aliphatic alcohol, with the formula C H3 O H (a methyl group linked to a hydroxyl group, often abbreviated as MeOH). It is ...
*:


Deprotection methods

*
Hydrogenation Hydrogenation is a chemical reaction between molecular hydrogen (H2) and another compound or element, usually in the presence of a catalyst such as nickel, palladium or platinum. The process is commonly employed to reduce or saturate organic ...
in the presence of the
palladium Palladium is a chemical element with the symbol Pd and atomic number 46. It is a rare and lustrous silvery-white metal discovered in 1803 by the English chemist William Hyde Wollaston. He named it after the asteroid Pallas, which was itself ...
catalyst


See also

* Benzylamine


References


External links

* * {{functional group, state=expanded Aryl groups Protecting groups