View source for Benzyl group

{{short description|Chemical group (–CH₂–C₆H₅)}}
{{distinguish|benzil|benzoyl|phenyl}}
[[File:Benzyl group V.9.svg|thumb|right|500px|{{color|blue|Benzyl group and derivatives}}: Benzyl group, benzyl [[Radical (chemistry)|radical]], [[benzyl amine]], [[benzyl bromide]], [[benzyl chloroformate]], and benzyl methyl ether. R = heteroatom, [[alkyl]], [[aryl]], [[allyl]] etc. or other substituents.]]

In [[organic chemistry]], '''benzyl''' is the [[substituent]] or molecular fragment possessing the structure {{chem2|R\sCH2\sC6H5}}. Benzyl features a [[benzene]] ring ({{chem2|C6H6}}) attached to a [[methylene group]] ({{chem2|\sCH2\s}}).<ref>{{cite book|last1=Carey |first1=F. A. |last2=Sundberg |first2=R. J. |title=Advanced Organic Chemistry, Part A: Structure and Mechanisms |url=https://archive.org/details/advancedorganicc00care_636 |url-access=limited |edition= 5th |publisher=Springer |location=New York, NY |date=2008 |pages=[https://archive.org/details/advancedorganicc00care_636/page/n829 806]–808, 312–313 |isbn=9780387448978}}</ref>

==Nomenclature==
In [[IUPAC nomenclature]], the prefix '''benzyl''' refers to a {{chem2|C6H5CH2}} substituent, for example [[benzyl chloride]] or [[benzyl benzoate]]. Benzyl is not to be confused with [[phenyl]] with the formula {{chem2|C6H5}}. 
The term '''benzylic''' is used to describe the position of the first carbon bonded to a benzene or other [[aromatic]] ring. For example, {{chem2|(C6H5)(CH3)2C+}} is referred to as a "benzylic" carbocation. The benzyl [[free radical]] has the formula {{chem2|C6H5CH2•}}. The benzyl cation or phenylcarbenium ion is the [[carbocation]] with formula {{chem2|C6H5CH2+}}; the benzyl anion or phenylmethanide ion is the [[carbanion]] with the formula {{chem2|C6H5CH2-}}. 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]]s and may exist as reactive intermediates.

===Abbreviations===
Benzyl is most commonly abbreviated Bn. For example, [[benzyl alcohol]] can be represented as BnOH. Less common abbreviations are Bzl and Bz, the latter of which is ambiguous as it is also the standard abbreviation for the [[benzoyl]] group {{chem2|C6H5C(O)\s}}. Likewise, benzyl should not be confused with the phenyl group {{chem2|C6H5\s}}, abbreviated Ph.

==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 {{chem2|C6H5CH2\sH}} 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.
{| class="wikitable" style = "text-align:center"
|-
!rowspan="2" |Bond
!rowspan="2" |Bond
!colspan="2" |Bond-dissociation energy<ref>{{cite journal |doi=10.1021/acs.chemrev.6b00664|title=The Essential Role of Bond Energetics in C–H Activation/Functionalization|year=2017|last1=Xue|first1=Xiao-Song|last2=Ji|first2=Pengju|last3=Zhou|first3=Biying|last4=Cheng|first4=Jin-Pei|journal=Chemical Reviews|volume=117|issue=13|pages=8622–8648|pmid=28281752}}</ref><ref name=Bord>{{cite journal |doi=10.1021/ja00051a010|title=Homolytic bond dissociation energies of the benzylic carbon-hydrogen bonds in radical anions and radical cations derived from fluorenes, triphenylmethanes, and related compounds|year=1992|last1=Zhang|first1=Xian-Man|last2=Bordwell|first2=Frederick G.|journal=Journal of the American Chemical Society|volume=114|issue=25|pages=9787–9792}}</ref>
!rowspan="2" |Comment
|-
!(kcal/mol)
!(kJ/mol)
|-
|{{chem2|C6H5CH2\sH}}
|benzylic C−H bond
|90
|377
|akin to allylic C−H bonds<br>such bonds show enhanced reactivity
|-
|{{chem2|H3C\sH}}
|[[methyl]] C−H bond
|105
|439
|one of the strongest aliphatic C−H bonds
|-
|{{chem2|C2H5\sH}}
|[[Ethyl group|ethyl]] C−H bond
|101
|423
|slightly weaker than {{chem2|H3C\sH}}
|-
|{{chem2|C6H5\sH}}
|[[phenyl]] C−H bond
|113
|473
|comparable to vinyl radical, rare
|-
|{{chem2|CH2\dCHCH2\sH}}
|[[allylic]] C–H bond
|89
|372
|similar to benzylic C-H
|-
|{{chem2|(C6H4)2CH\sH}}
|[[fluorenyl]] C–H bond
|80
|
|more activated vs diphenylmethyle ([[pKa]] = 22.6)
|-
|{{chem2|(C6H5)2CH\sH}}
|[[Benzhydryl compounds|diphenylmethyl]] C–H bond
|82
|
|"doubly benzylic" ([[pKa]] = 32.2)
|-
|{{chem2|(C6H5)3C\sH}}
|[[trityl]] C–H bond
|81
|339
|"triply benzylic"
|-
|}

The weakness of the C−H bond reflects the stability of the benzylic radical. For related reasons, benzylic substituents exhibit enhanced reactivity, as in [[KMnO4#Organic chemistry|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]]:
:<chem>CH3C6H4CH3 + 3 O2 -> HO2CC6H4CO2H + 2 H2O</chem>
Millions of tonnes of terephthalic acid are produced annually by this method.<ref>{{Ullmann|first=Richard J. |last=Sheehan |title=Terephthalic Acid, Dimethyl Terephthalate, and Isophthalic Acid |doi=10.1002/14356007.a26_193}}</ref>

=== Functionalization at the benzylic position ===
In a few cases, these benzylic transformations occur under conditions suitable for lab synthesis.  The [[Wohl–Ziegler bromination|Wohl-Ziegler reaction]] will brominate a benzylic C–H bond: ({{chem2|ArCHR2 -> ArCBrR2}}).<ref>{{Cite book|title=Organic chemistry : structure and function|last=C.|first=Vollhardt, K. Peter|others=Schore, Neil Eric, 1948-|isbn=9781319079451|edition= 8e|location=New York|oclc=1007924903|date = 2018-01-29}}</ref>  Any non-tertiary benzylic alkyl group will be oxidized to a carboxyl group by aqueous potassium permanganate ({{chem2|KMnO4}}) or concentrated nitric acid ({{chem2|HNO3}}): ({{chem2|ArCHR2 -> ArCOOH}}).<ref>{{Cite book|title=Principles of organic synthesis.|last=Chandler)|first=Norman, R. O. C. (Richard Oswald|date=1993|publisher=Blackie Academic & Professional|others=Coxon, J. M. (James Morriss), 1941-|isbn=978-0751401264|edition= 3rd.|location=London|oclc=27813843}}</ref>  Finally, the complex of [[chromium trioxide]] and [[3,5-Dimethylpyrazole|3,5-dimethylpyrazole]] ({{chem2|CrO3\sdmpyz}}) will selectively oxidize a benzylic methylene group to a carbonyl: ({{chem2|ArCH2R -> ArC(O)R}}).<ref>{{Citation|last=Johnston|first=Jeffrey N.|title=Chromium(VI) Oxide–3,5-Dimethylpyrazole|date=2001|encyclopedia=Encyclopedia of Reagents for Organic Synthesis|publisher=American Cancer Society|language=en|doi=10.1002/047084289x.rc170|isbn=9780470842898}}</ref> [[2-Iodoxybenzoic acid|2-iodoxybenzoic acid]] in DMSO performs similarly.<ref>{{Cite journal|last1=Baran|first1=Phil S.|last2=Zhong|first2=Yong-Li|date=2001-04-01|title=Selective Oxidation at Carbon Adjacent to Aromatic Systems with IBX|journal=Journal of the American Chemical Society|volume=123|issue=13|pages=3183–3185|doi=10.1021/ja004218x|pmid=11457049|issn=0002-7863}}</ref>

==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.<ref name=":0"/>
=== Alcohol protection ===
Benzyl is commonly used in organic synthesis as a robust protecting group for [[alcohol (chemistry)|alcohol]]s and [[carboxylic acid]]s.

* Treatment of alcohol with a strong base such as powdered [[potassium hydroxide]] or [[sodium hydride]] and benzyl halide ([[benzyl chloride|BnCl]] or [[benzyl bromide|BnBr]])<ref name=":0">{{Cite book|title=Greene's Protective Groups in Organic Synthesis|edition= 4th|publisher=Wiley Online Library|last1=Wuts|first1=Peter G. M.|last2=Greene|first2=Theodora W.|doi=10.1002/0470053488|year = 2006|isbn = 9780470053485|s2cid= 83393227}}</ref><ref>{{Cite journal|last1=Fukuzawa|first1=Akio|last2=Sato|first2=Hideaki|last3=Masamune|first3=Tadashi|date=1987-01-01|title=Synthesis of (±)-prepinnaterpene, a bromoditerpene from the red alga Yamada|journal=Tetrahedron Letters|volume=28|issue=37|pages=4303–4306|doi=10.1016/S0040-4039(00)96491-8}}</ref>
*:[[File:BnProtectedalcohol.png|none|455x455px]]
* Monobenzylation of [[diol]]s can be achieved using [[silver(I) oxide|Ag<sub>2</sub>O]] in [[dimethylformamide]] (DMF) at ambient to elevated temperatures<ref>{{Cite journal|last1=Van Hijfte|first1=Luc|last2=Little|first2=R. Daniel|date=1985-10-01|title=Intramolecular 1,3-diyl trapping reactions. A formal total synthesis of (±)-coriolin|journal=The Journal of Organic Chemistry|volume=50|issue=20|pages=3940–3942|doi=10.1021/jo00220a058|issn=0022-3263}}</ref>
* [[Primary alcohol]]s can be selectively benzylated in presence of phenol functional groups using [[Metal acetylacetonates|Cu(acac)<sub>2</sub>]]<ref>{{Cite journal|last1=Sirkecioglu|first1=Okan|last2=Karliga|first2=Bekir|last3=Talinli|first3=Naciye|date=2003-11-10|title=Benzylation of alcohols by using bis[acetylacetonato]copper as catalyst|journal=Tetrahedron Letters|volume=44|issue=46|pages=8483–8485|doi=10.1016/j.tetlet.2003.09.106}}</ref>

===Deprotection methods ===
Benzyl ethers can be removed under ''[[redox|reductive]] conditions'', ''[[oxidative]] conditions'', and the use of ''Lewis acids''.<ref name=":0" />

* Removed using [[hydrogenolysis]]<ref>{{Cite journal|last1=Smith|first1=Amos B.|last2=Zhu|first2=Wenyu|last3=Shirakami|first3=Shohei|last4=Sfouggatakis|first4=Chris|last5=Doughty|first5=Victoria A.|last6=Bennett|first6=Clay S.|last7=Sakamoto|first7=Yasuharu|date=2003-03-01|title=Total Synthesis of (+)-Spongistatin 1. An Effective Second-Generation Construction of an Advanced EF Wittig Salt, Fragment Union, and Final Elaboration|journal=Organic Letters|volume=5|issue=5|pages=761–764|doi=10.1021/ol034037a|issn=1523-7060|pmid=12605509}}</ref>
*:[[File:BnEtherExample.png|none|626x626px]]
* Single electron process with [[sodium|Na]]/[[ammonia|NH<sub>3</sub>]] or [[lithium|Li]]/NH<sub>3</sub>

* Benzyl protecting groups can be removed using a wide range of oxidizing agents including:
** [[chromium trioxide|CrO<sub>3</sub>]]/[[acetic acid]] at ambient temperature
** [[Ozone]]
** [[N-Bromosuccinimide|''N''-Bromosuccinimide]] (NBS)
** [[N-Iodosuccinimide|''N''-Iodosuccinimide]] (NIS)

* [[Trimethylsilyl]] iodide (Me<sub>3</sub>SiI) in [[dichloromethane]] at ambient temperature (selectivity can be achieved under specific conditions)

===The ''p''-methoxybenzyl protecting group===
''p''-Methoxybenzyl ('''PMB''') is used as a [[protecting group]] for [[alcohols]] in [[organic synthesis]] ([[4-Methoxybenzylthiol]] is used to protect thiols).
[[File:PMB_Ether.png|thumb|The ''p''-methoxybenzyl group]]

* Strong base such as powdered [[potassium hydroxide]] or [[sodium hydride]] and ''p''-methoxybenzyl halide (chloride or bromide)<ref>{{Cite journal|last1=Marco|first1=José L.|last2=Hueso-Rodríguez|first2=Juan A.|date=1988-01-01|title=Synthesis of optically pure 1-(3-furyl)-1,2-dihydroxyethane derivatives|journal=Tetrahedron Letters|volume=29|issue=20|pages=2459–2462|doi=10.1016/S0040-4039(00)87907-1}}</ref><ref>{{Cite journal|last1=Takaku|first1=Hiroshi|last2=Kamaike|first2=Kazuo|last3=Tsuchiya|first3=Hiromichi|date=1984-01-01|title=Oligonucleotide synthesis. Part 21. Synthesis of ribooligonucleotides using the 4-methoxybenzyl group as a new protecting group for the 2′-hydroxyl group|journal=The Journal of Organic Chemistry|volume=49|issue=1|pages=51–56|doi=10.1021/jo00175a010|issn=0022-3263}}</ref>
* 4-methoxybenzyl-2,2,2-trichloroacetimidate can be used to install the PMB group in presence of:
**[[Scandium(III) trifluoromethanesulfonate|Scandium (III) triflate]] (Sc(OTf)<sub>3</sub>) in toluene at 0&nbsp;°C<ref>{{Cite journal|last1=Trost|first1=Barry M.|last2=Waser|first2=Jerome|last3=Meyer|first3=Arndt|date=2007-11-01|title=Total Synthesis of (−)-Pseudolaric Acid B|journal=Journal of the American Chemical Society|volume=129|issue=47|pages=14556–14557|doi=10.1021/ja076165q|issn=0002-7863|pmc=2535803|pmid=17985906}}</ref>
** [[Trifluoromethanesulfonic acid]] (TfOH) in [[dichloromethane]] at 0&nbsp;°C<ref>{{Cite journal|last1=Mukaiyama|first1=Teruaki|last2=Shiina|first2=Isamu|last3=Iwadare|first3=Hayato|last4=Saitoh|first4=Masahiro|last5=Nishimura|first5=Toshihiro|last6=Ohkawa|first6=Naoto|last7=Sakoh|first7=Hiroki|last8=Nishimura|first8=Koji|last9=Tani|first9=Yu-ichirou|date=1999-01-04|title=Asymmetric Total Synthesis of Taxol\R|journal=Chemistry – A European Journal|language=en|volume=5|issue=1|pages=121–161|doi=10.1002/(SICI)1521-3765(19990104)5:1<121::AID-CHEM121>3.0.CO;2-O |issn=1521-3765 |doi-access=free}}</ref>
**:[[File:PMBAlcohol.png|none|676x676px]]

==== Deprotection methods ====
* 2,3-Dichloro-5,6-dicyano-''p''-benzoquinone (DDQ)<ref>{{Cite journal|last1=Hanessian|first1=Stephen|last2=Marcotte|first2=Stéphane|last3=Machaalani|first3=Roger|last4=Huang|first4=Guobin|date=2003-11-01|title=Total Synthesis and Structural Confirmation of Malayamycin A: A Novel Bicyclic ''C''-Nucleoside from Streptomyces malaysiensis|journal=Organic Letters|volume=5|issue=23|pages=4277–4280|doi=10.1021/ol030095k|issn=1523-7060|pmid=14601979}}</ref>
*:[[File:PMBDeprotection.png|none|674x674px]]
* 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]] for [[amine]]s in [[organic synthesis]].  Other methods exist.<ref name=":0" />

* Aqueous [[potassium carbonate]] and benzyl halide ([[benzyl chloride|BnCl]], [[benzyl bromide|BnBr]]) in [[methanol]]<ref>{{Cite journal|last1=Kuehne|first1=Martin E.|last2=Xu|first2=Feng|date=1993-12-01|title=Total synthesis of strychnan and aspidospermatan alkaloids. 3. The total synthesis of (±)-strychnine|journal=The Journal of Organic Chemistry|volume=58|issue=26|pages=7490–7497|doi=10.1021/jo00078a030|issn=0022-3263}}</ref>
*:[[File:Bn_protection_with_bnbr.png|none|609x609px]]
* [[Benzaldehyde]], 6&nbsp;M [[Hydrogen chloride|HCl]] and [[Sodium cyanoborohydride|NaBH<sub>3</sub>CN]] in [[methanol]]<ref>{{Cite journal|last1=Cain|first1=Christian M.|last2=Cousins|first2=Richard P. C.|last3=Coumbarides|first3=Greg|last4=Simpkins|first4=Nigel S.|date=1990-01-01|title=Asymmetric deprotonation of prochiral ketones using chiral lithium amide bases|journal=Tetrahedron|volume=46|issue=2|pages=523–544|doi=10.1016/S0040-4020(01)85435-1}}</ref>
*:[[File:Bn_protection_with_benzaldehyde.png|none|532x532px]]

====Deprotection methods ====
* [[Hydrogenation]] in the presence of the [[palladium]] catalyst<ref>{{Cite journal|last1=Zhou|first1=Hao|last2=Liao|first2=Xuebin|last3=Cook|first3=James M.|date=2004-01-01|title=Regiospecific, Enantiospecific Total Synthesis of the 12-Alkoxy-Substituted Indole Alkaloids, (+)-12-Methoxy-Na-methylvellosimine, (+)-12-Methoxyaffinisine, and (−)-Fuchsiaefoline|journal=Organic Letters|volume=6|issue=2|pages=249–252|doi=10.1021/ol0362212|issn=1523-7060|pmid=14723540}}</ref>

[[File:QIGLEZ.svg|thumb|left|Structure of [[tetrabenzylzirconium]] with H atoms omitted for clarity.<ref name=Parkin>{{cite journal|doi=10.1021/om300820b|title=Highly Variable Zr–CH2–Ph Bond Angles in Tetrabenzylzirconium: Analysis of Benzyl Ligand Coordination Modes|journal=Organometallics|volume=31|issue=23|pages=8208–8217|year=2012|last1=Rong|first1=Yi|last2=Al-Harbi|first2=Ahmed|last3=Parkin|first3=Gerard}}</ref>]]

==See also==
* [[Benzylamine]]

==References==
{{Reflist|30em}}

==External links==
{{Commonscat}}
*{{Portal-inline|Chemistry}}
*{{wikiquote-inline}}

{{functional group|state=expanded}}

[[Category:Aryl groups]]
[[Category:Protecting groups]]