Benzyl

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

Contents 1 Nomenclature 1.1 Abbreviations 2 Reactivity of benzylic centers 3 Benzyl protective groups 4 References

Nomenclature

The term benzyl refers most commonly to benzyl compounds, such as benzyl chloride or benzyl benzoate. Benzyl also refers to a free radical with the formula C₆H₅CH₂. The benzyl carbocation has the formula C₆H₅CH₂⁺. The benzyl carbanion has the formula C₆H₅CH₂^-. None of these species have significant existence under normal conditions, but they are useful references for discussion of mechanisms.

Sometimes, benzyl and phenyl are confused, but their formulas and behavior are very different. The term benzylic refers to the position on a carbon skeleton next to a phenyl or other aromatic ring.

Abbreviations

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)-.

Reactivity of benzylic centers

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

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]
• 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

1. ^ 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.
2. ^ 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
3. ^ DeSelms, R. H.; Benzyl Phenyl Ether Compounds; Enigen Science Publishing: Washington, DC, 2008.
4. ^ 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
5. ^ Protecting groups Krzysztof Jarowicki and Philip Kocienski J. Chem. Soc., Perkin Trans. 1, 1998, 4005–4037 4005 doi:10.1039/a803688h
6. ^ 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.