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17 17 Allylic and Benzylic Reactivity

An allylic group is a group on a carbon adjacent to a double bond. A benzylic group is a group on a carbon adjacent to a benzene ring or substituted benzene ring. allylic chlorine benzylic hydroxy group

Cl OH

H2C A CH "CH CH3 "CH CH3 L L cL L allylic hydrogen benzylic hydrogen In many situations allylic and benzylic groups are unusually reactive. This chapter examines what happens when some familiar reactions occur at allylic and benzylic positions and discusses the reasons for allylic and benzylic reactivity. This chapter also presents some reac- tions that occur only at the allylic and benzylic positions. Finally, Sec. 17.6 will show that al- lylic reactivity is also important in some chemistry that occurs in living organisms.

PROBLEMS 17.1 Identify the allylic carbons in each of the following structures.

(a) (b) H %

q `w CH H 3

17.2 Identify the benzylic carbons in each of the following structures. c 0 (a) H3C CH3 (b) H3C M M L

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17.1 REACTIONS INVOLVING ALLYLIC AND BENZYLIC CARBOCATIONS 789

REACTIONS INVOLVING ALLYLIC AND 17.1 BENZYLIC CARBOCATIONS

Recall that allylic carbocations are resonance-stabilized (Sec. 15.4B). The simplest example of an allylic cation is the allyl cation itself:

H2C ACH CH| 2 H2C| CH A CH2 (17.1) resonanceL structures of the allyl cationL

These resonance structures symbolize the delocalization of electrons and electron deficiency (along with the associated positive charge) that result from the overlap of 2p orbitals to form molecular orbitals, as shown in Fig. 15.9, p. 703. Benzylic carbocations are also resonance-stabilized. The benzyl cation is the simplest ex- ample of a benzylic cation:

CH| 2 CH2 CH2 | CH2 % ( ( ( (17.2) i a | | f resonance structures of the benzyl cation

The resonance structures of the benzyl cation symbolize the overlap of 2p orbitals of the ben- zylic carbon and the benzene ring to form bonding MOs. As these structures show, the elec- tron deficiency and resulting positive charge on a benzylic carbocation are shared not only by the benzylic carbon, but also by alternate carbons of the ring. As with the allyl cation (Sec. 15.4B), the resonance structures of the benzyl cation correctly account for the distribution of positive charge that is calculated from MO theory and shown by the EPM:

* * * * = sites of partial positive charge *

EPM of benzyl cation

The resonance energy (p. 704) of the benzyl cation calculated from MO theory (over and above that of the benzene ring itself) is about 0.72b, which is about 90% of the resonance en- ergy of the allyl cation. In other words, the resonance stabilizations of the benzyl and allyl cations are about the same. The structures and stabilities of allylic and benzylic carbocations have important conse- quences for reactions in which they are involved as reactive intermediates. First, reactions in which benzylic or allylic carbocations are formed as intermediates are generally considerably faster than analogous reactions involving comparably substituted nonallylic or nonbenzylic

carbocations. This point is illustrated by the relative rates of SN1 solvolysis reactions, shown in Tables 17.1 and 17.2, p. 790. For example, the tertiary allylic alkyl halide in the first entry of Table 17.1 reacts more than 100 times faster than the tertiary nonallylic alkyl halide in the 17_BRCLoudon_pgs5-0.qxd 12/9/08 11:29 AM Page 790

790 CHAPTER 17 • ALLYLIC AND BENZYLIC REACTIVITY

TABLE 17.1 Comparison of SN1 Solvolysis Rates of Allylic and Nonallylic Alkyl Halides

44.6 °C R Cl C2H5OH H2O 50% aqueous ethanol R OC2H5 R OH HCl L ++ L ++L Alkyl chloride R—Cl Relative rate

CH3

H2C A CH" C Cl 162 LL "CH3

H3C

$C A CH CH2 Cl 38 LL H3C)

CH3

CH3CH2 "C Cl (1.00) LL "CH3

H3C

$CH CH2 CH2 Cl 0.00002 LLL < H3C)

TABLE 17.2 Comparison of SN1 Solvolysis Rates of Benzylic and Nonbenzylic Alkyl Halides

25 °C R Cl H O R OH HCl 2 90% aqueous acetone L + L + Alkyl chloride R—Cl Common name Relative rate

(CH3)3C Cl tert-butyl chloride (1.0) L Ph CH Cl a-phenethyl chloride 1.0 L L "CH3

CH3

Ph "C Cl tert-cumyl chloride 620 L L "CH3

Ph2CH Cl benzhydryl chloride 200* L Ph3C Cl trityl chloride 600,000 L > *In 80% aqueous ethanol.

third entry. A comparison of the first and third entries of Table 17.2 shows the effect of benzylic substitution. tert-Cumyl chloride, the third entry, reacts more than 600 times faster than tert-butyl chloride, the first entry. The greater reactivities of allylic and benzylic halides result from the stabilities of the car- bocation intermediates that are formed when they react. For example, tert-cumyl chloride (the third entry of Table 17.2) ionizes to a carbocation with four important resonance structures: 17_BRCLoudon_pgs5-0.qxd 12/9/08 11:29 AM Page 791

17.1 REACTIONS INVOLVING ALLYLIC AND BENZYLIC CARBOCATIONS 791

CH3

"C Cl cL L 21 3 "CH3

CH3 CH3 CH3 CH3 | C| A C A C A C Cl ) ) ) ) _ cL n | l m 3 21 3 ΄ $CH3 $CH3 $CH3 $CH3 ΄ | resonance-stabilized carbocation (17.3) Ionization of tert-butyl chloride, on the other hand, gives the tert-butyl cation, a carbocation with only one important contributing structure.

CH3 CH3

H3CC" Cl H3CC"| Cl _ (17.4) LL2 3 L 3 2 3 "CH3 2 "CH3 2 tert-butyl chloride The benzylic cation is more stable relative to its alkyl halide starting material than is the tert- butyl cation, and application of Hammond’s postulate predicts that the more stable carboca- tion should be formed more rapidly. A similar analysis explains the reactivity of allylic alkyl halides. Because of the possibility of resonance, ortho and para substituent groups on the benzene

ring that activate electrophilic aromatic substitution further accelerate SN1 reactions at the benzylic position: CH3 CH3

"C Cl CH3O "C Cl (17.5) cL L LcL L "CH3 "CH3 relative solvolysis rates 1 3400 (90% aqueous acetone, 25 °C) The carbocation derived from the ionization of the p-methoxy derivative in Eq. 17.5 not only has the same types of resonance structures as the unsubstituted compound, shown in Eq. 17.3, but also an additional structure (red) in which charge can be delocalized onto the substituent group itself:

CH3 CH3 CH3

CH3O C|) CH3O A C) CH3O AC) 21 LcL 21 Ln 21 Ll| $CH $CH $CH 3 | 3 3

CH3 CH3 | | CH3O A A C) CH3O A C) 2 l 21 L/ $CH3 $CH3 charge is shared by oxygen (17.6) Other reactions that involve carbocation intermediates are accelerated when the carbocations are allylic or benzylic. Thus, the dehydration of an alcohol (Sec. 10.1) and the reaction of an 17_BRCLoudon_pgs5-0.qxd 12/9/08 11:29 AM Page 792

792 CHAPTER 17 • ALLYLIC AND BENZYLIC REACTIVITY

alcohol with a hydrogen halide (Sec. 10.2) are also faster when the alcohol is allylic or benzylic. For example, most alcohols require forcing conditions or Lewis acid catalysts to react with HCl to give alkyl chlorides, but such conditions are unnecessary when benzylic alcohols react with HCl. The addition of hydrogen halides to conjugated dienes also reflects the stability of allylic carbocations. Recall that protonation of a conjugated diene gives the allylic carbocation rather than its nonallylic isomer because the allylic carbocation is formed more rapidly (Sec. 15.4A). A second consequence of the involvement of allylic carbocations as reactive intermediates is that in many cases more than one product can be formed. More than one product is possible because the positive charge (and electron deficiency) is shared between two carbons. Nucle- ophiles can react at either of the electron-deficient carbon atoms and, if the two carbons are not equivalent, two different products result.

(CH ) C A CH CH Cl (CH ) C A CH CH (CH ) C CHA CH Cl 3 2 2 ͫ 3 2 2 3 2 2ͬ _ L L L an allylic carbocation L +

H2O 2

(CH3)2C A CHCH2 (CH3)2C CH A CH2

+ L .. O H .. O H H H

H2O H2O

2 1 2 1 H3O.. (CH3)2C A CH CH2 (CH3)2C CHA CH2

+ L L

.. ..

.. OH.. OH (15% of product) (85% of product) (17.7) The two products are derived from one allylic carbocation that has two resonance forms. Recall that similar reasoning explains why a mixture of products (1,2- and 1,4-addition products) is ob- tained in the reactions of hydrogen halides with conjugated alkenes (Sec. 15.4A).

We might expect that several substitution products in the SN1 reactions of benzylic alkyl halides might be formed for the same reason. CH 3 CH3 CH3 CH3 H O " 2 | A A C Cl C) C) C) Cl_ cL L cL n | x "CH3 $CH3 | $CH3 $CH3

H2O

CH3 CH3 % CH3 H HCl "C OH A C) A C)

HO% + cL L + n% + " $CH3 $CH3 CH3 % OH (the only substitution H product formed) (not formed) (17.8) 17_BRCLoudon_pgs5-0.qxd 12/9/08 11:29 AM Page 793

17.2 REACTIONS INVOLVING ALLYLIC AND BENZYLIC RADICALS 793

As Eq. 17.8 shows, the products derived from the reaction of water at the ring carbons are not formed. The reason is that these products are not aromatic and thus lack the stability associ- ated with the aromatic ring. Aromaticity is such an important stabilizing factor that only the aromatic product (red) is formed.

PROBLEMS 17.3 Predict the order of relative reactivities of the compounds within each series in SN1 solvoly- sis reactions, and explain your answers carefully.

(a) Cl Cl Cl "CH CH3 $ "CH CH3 H3C "CH CH3 cL L cL L LcL L

CH3O (1) (2) (3)

(b) CH3 CH3 CH3 "C Cl $ "C Cl Cl "C Cl cL L cL L LcL L "CH "CH "CH 3 Cl 3 3 (1) (2) (3)

17.4 Give the structure of an isomer of the allylic halide reactant in Eq. 17.7 that would react with

water in an SN1 solvolysis reaction to give the same two products. Explain your reasoning. 17.5 Why is trityl chloride much more reactive than the other alkyl halides in Table 17.2?

17.2 REACTIONS INVOLVING ALLYLIC AND BENZYLIC RADICALS

An allylic radical has an unpaired electron at an allylic position. Allylic radicals are resonance-stabilized and are more stable than comparably substituted nonallylic radicals. The simplest allylic radical is the allyl radical itself:

H CA CH CH H C CH ACH 2 8 2 2 8 2 (17.9) resonanceL structures of the allyl radicalL

Similarly, a benzylic radical, which has an unpaired electron at a benzylic position, is also resonance-stabilized. The benzyl radical is the prototype:

8 CH8 2 A CH2 A CH2 A CH2 ΄ cL n 8 x / ΄ resonance8 structures of the benzyl radical (17.10) These resonance structures symbolize the delocalization (sharing) of the unpaired electron that results from overlap of carbon 2p orbitals to form molecular orbitals. The enhanced stabilities of allylic and benzylic radicals can be experimentally demonstrated with bond dissociation energies. The bond dissociation energies of allylic and nonallylic hydro-