{{Short description|Chemical group (–CH2–C6H5)}} {{distinguish|benzil|benzoyl|phenyl}} [[File:Chemical structural formulas of benzyl group.svg|thumb|right|500px|{{color|blue|Benzyl group and derivatives}}: Benzyl group, benzyl 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 mechanisms 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 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}} |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 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 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 ({{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 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 alcohols and carboxylic acids.

* Treatment of alcohol with a strong base such as powdered potassium hydroxide or sodium hydride and benzyl halide (BnCl or 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> *:none|455x455px * Monobenzylation of diols can be achieved using 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 alcohols can be selectively benzylated in presence of phenol functional groups using 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 ''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> *:none|626x626px * Single electron process with Na/NH<sub>3</sub> or Li/NH<sub>3</sub>

* Benzyl protecting groups can be removed using a wide range of oxidizing agents including: ** CrO<sub>3</sub>/acetic acid at ambient temperature ** Ozone ** ''N''-Bromosuccinimide (NBS) ** ''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). 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) 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> **: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> *: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 amines in organic synthesis. Other methods exist.<ref name=":0" />

* Aqueous potassium carbonate and benzyl halide (BnCl, 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> *:none|609x609px * Benzaldehyde, 6&nbsp;M HCl and 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> *: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