Mechanism of the oxidation of para-substituted 1-phenylethanols with sodium hypochlorite in acetic acid

Article abstract of DOI:10.1016/S0040-4039(00)00296-3

The ρ-value of -1.8 for the oxidation of para-substituted 1- phenylethanols by sodium hypochlorite in acetic acid suggests that ketone is formed directly from alcohol by loss of a hydride. The kinetic isotope effect is 3.0. When the disappearance of oxidant is followed by iodometric titration, 5-nonanol is oxidized about 20 times faster than 1-butylpentyl hypochlorite decomposes. However, when NaCl is added to the alkyl hypochlorite, the reaction rates are about the same. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)00296-3

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 2759–2763
Mechanism of the oxidation of para-substituted 1-phenylethanols
with sodium hypochlorite in acetic acid
Ayano Sakai, David G. Hendrickson and William H. Hendrickson ∗
Department of Chemistry, University of Dallas, Irving, TX 75062, USA
Received 10 January 2000; revised 11 February 2000; accepted 13 February 2000
Abstract
The ρ-value of −1.8 for the oxidation of para-substituted 1-phenylethanols by sodium hypochlorite in acetic
acid suggests that ketone is formed directly from alcohol by loss of a hydride. The kinetic isotope effect is 3.0.
When the disappearance of oxidant is followed by iodometric titration, 5-nonanol is oxidized about 20 times faster
than 1-butylpentyl hypochlorite decomposes. However, when NaCl is added to the alkyl hypochlorite, the reaction
rates are about the same. © 2000 Elsevier Science Ltd. All rights reserved.
Keywords: alcohols; oxidation; mechanisms; substituent effects; alkyl hypochlorite.
Sodium hypochlorite (bleach) in acetic acid provides an inexpensive and relatively non-toxic method
for alcohol oxidation.1 The previously suggested mechanism proposed the rapid formation of an alkyl
hypochlorite intermediate, which is converted to ketone in an E2 type reaction.1 Our study of substituent
effects on this reaction indicates that an alternative mechanism may be occurring.
A series of para-substituted 1-phenylethanols was treated with a limiting amount of bleach in acetic
acid.2 Since 1-phenylethanol and 1-(4-methylphenyl)ethanol gave 6 and 20% yields of ring chlorinated
products, respectively, 5-nonanol was used as the reference alcohol, and the relative reactivities were
adjusted to account for ring chlorination.3 The data is given in Table 1. A Hammett plot gives a ρ-value
of −1.80±0.06 (r=0.9878).
Alcohols also have been oxidized with bleach in a two-phase system using a phase transfer catalyst
(PTC).4 For comparison to oxidation in acetic acid, we measured substituent effects for bleach oxidations
in ethyl acetate. Since ring chlorination was not a problem in the two-phase reaction, 1-phenylethanol
was used as the reference.5 The results, shown in Table 1, give a ρ-value of +0.98±0.02 (r=0.9943). This
agrees very well with the ρ-value of +1.03 reported by Bradley for the oxidation of benzyl alcohols.6 We
have also measured kinetic isotope effects for these reactions with 1-phenylethanol-d1 using 5-nonanol
as the reference. The k.i.e. values are 3.0 in acetic acid and 3.6 in ethyl acetate. Therefore, in either
∗
Corresponding author. E-mail: hendrick@chem.udallas.edu (W. H. Hendrickson)
0040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)00296-3
tetl 16576

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Table 1
Oxidation of para-substituted 1-phenylethanol by bleach in acetic acid and ethyl acetate
solvent, the carbon–hydrogen bond is being broken in the transition state of the rate determining step but
the electronic effects of substituents are opposite.
It is apparent that these two reactions have different mechanisms. Although it has not been established,
the likely mechanism for the two-phase system is an E2 elimination of an intermediate alkyl hypochlorite.
We have shown by 1H NMR that 1-methyl-1-phenylethyl hypochlorite is rapidly formed in the dichloro-
methane–bleach–PTC reaction of 2-phenyl-2-propanol.7 An E2 type reaction should be accelerated by
electron withdrawing groups. Positive ρ-values have been reported for the formation of benzaldehyde in
the reaction of benzyl nitrate with ethoxide (ρ=+3.40)8 and for eliminations of a number of 2-substituted-
1-phenylethanes.9 If the rate determining step in the bleach/acetic acid system was elimination of HCl
from an alkyl hypochlorite, as shown in Eq. (1), the ρ-value for the reaction should be positive.
(1)
An alternate mechanism for the bleach/acetic acid oxidation consistent with the observed substituent
effects is shown in Eqs. (2) and (3). An alkyl hypochlorite intermediate is rapidly formed, but the reaction
is reversible (Eq. (2)). Chloride ions react with alkyl hypochlorites in acidic solution to give chlorine.10
While elimination of HCl from the alkyl hypochlorite is possible (Eq. (1)), we believe it is a relatively
slow reaction, and the oxidation is the result of a fast concerted reaction of alcohol with chlorine (Eq.
(3)). Although hypochlorous acid as well as chlorine could be the oxidant, earlier work by Kudesia and
Mukherjee indicates chlorine.11
(2)

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(3)
Negative ρ-values have been reported for the oxidations of benzyl alcohol with quinolinium
dichromate (ρ=−1.67)12 and for oxidations of substituted ethanols with pyridinium chlorochromate
(ρ*=−1.75).13 The proposed mechanism for these reactions is an intramolecular loss of hydride from
a chromate ester.12,14 Cyclic mechanisms as in Eq. (3) also have been suggested for the oxidations of
benzyl alcohol with benzyltrimethylammonium tribromide (ρI=−1.07, ρR=−1.36)15 and for the reaction
of 1-phenylethanol with t-butyl hypochlorite (ρ=−0.66).16 A ρ-value of −1.66 was reported for the
oxidation of benzyl alcohol with chloramine T, which forms chlorine in situ.17
For our mechanism to be correct, alkyl hypochlorite must be formed reversibly and must react
relatively slowly with water. We have followed the disappearance of oxidant by iodometric titration
for bleach reactions and for reactions of 1-butylpentyl hypochlorite (1) in the absence of bleach.18 Our
results are given in Table 2. Graphs of ln [oxidant] versus time were linear for all reactions except for the
slower reactions of 1 without added NaCl (6–8). For these slower reactions, the rate increased after an
induction period of at least 35 min;19 the reported rate constants are for the initial slow reactions.
Table 2
Rate constants for reactions of 5-nonanol and 1a
The first five entries in Table 2 show the effect of changing alcohol concentration. When alcohol is in
excess, the reaction rate is approximately first order in alcohol. For an E2 reaction of a rapidly formed
alkyl hypochlorite, the reaction rate should be independent of alcohol concentration when alcohol is in
excess. Furthermore, if Eq. (1) were the rate determining step, the decomposition of 1 in aqueous acetic
acid (6) should have the same rate constant as alcohol oxidation (5). Bleach oxidation, however, is 20
times faster than the disappearance of oxidant in the reaction of 1. The addition of sodium acetate (7),
which would be formed in the reaction of sodium hypochlorite with acetic acid, has little effect on the
rate constant for reaction of 1.
Bleach contains NaCl,20 and when NaCl is added to 1 (9,10), the rate constant is essentially the same
as that of alcohol in bleach. We believe that the added chloride ions rapidly react with 1 to give alcohol
and chlorine. When fluoride, which does not react with alkyl hypochlorites,10a is added to 1 (8), the rate

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is not increased. Furthermore, the decomposition of 1 in acetic acid without added chloride would be
expected to exhibit autocatalytic behavior; the initial reaction is slow until chloride is formed and then
the reaction accelerates.
In summary, the rate acceleration by chloride supports the reversibility of Eq. (2). The initial stability
of 1 in the absence of chloride shows that reaction of 1 with water is slower than the reaction of 5-nonanol
with bleach. The ρ-value of −1.8 is consistent with the reaction of chlorine or hypochlorous acid with
alcohol being the rate determining step. The mechanism also explains the necessity of a chlorocarbon
solvent in the preparation of alkyl hypochlorites from secondary alcohols.10b,c Extraction of the alkyl
hypochlorite, as it is formed, into the organic layer isolates it from the chloride ions in bleach and prevents
the reverse reaction.
Acknowledgements
The authors thank Robert Landolt for helpful discussions. Financial support was provided by the
Robert A. Welch Foundation through a Chemistry Departmental Research Grant (BA0015) and the
O’Hara Chemical Sciences Institute of the University of Dallas.
References
1. Mohrig, J. R.; Nienhuls, D. M.; Linck, C. F.; Zoeren, C. V.; Fox, B. B.; Mahaffy, P. G. J. Chem. Ed. 1985, 62, 519–521 and
references cited therein.
2. A 10 mL acetic acid solution containing 0.10 M 5-nonanol, 0.10 M substituted 1-phenylethanol and 0.10 M chlorobenzene
was divided into two 5.0 mL aliquots. One aliquot was stirred with 0.70 mL bleach at 21°C for 30 min. Both aliquots were
worked up by adding 10 mL of water and 10 mL of CH2Cl2. The CH2Cl2 layer was separated and washed with 10% aqueous
sodium carbonate. Relative areas were measured by GC and relative reactivities were calculated by krel=log (rel. area At/rel.
area A0)/log (rel. area Bt/rel. area B0) where A is substituted 1-phenylethanol and B is 5-nonanol.
3. The relative reactivity was corrected by kcorr=krel/[1+(rel. area of ring chlorinated compounds)/(rel. area of ketone)].
4. (a) Lee, G. A.; Freedman, H. H. Isr. J. Chem. 1985, 26, 229–234. (b) Mirafzal, G. A.; Lozeva, A. M. Tetrahedron Lett. 1998,
39, 7263–7266.
5. A 20 mL solution of bleach buffered with 0.2 M sodium carbonate at pH 9 with 0.075 mmol tetra-n-butylammonium
hydrogen sulfate was added to 15 mL ethyl acetate containing 0.05 M 1-phenyl-1-ethanol, 0.05 M chlorobenzene internal
standard and 0.05 M substituted 1-phenylethanol at 21°C. Rate constants are the slope of a graph of ln[alcohol]t versus time.
6. Bradley, L. M.; Lesica, J. M.; Albertson, K. B. React. Kinet. Catal. Lett. 1997, 62, 3–7.
7. Dailey, J. I.; Hays, R. S.; Lee, H.; Mitchell, R. M.; Ries, J. J.; Landolt, R. G.; Husmann, H. H.; Lockridge, J. B.; Hendrickson,
W. H. J. Org. Chem., in press.
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(c) Walling, C.; Clark, R. T. J. Am. Chem. Soc. 1974, 96, 4530–4534.
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14. Mahanti, M. K.; Nongkynrih, I. Bull. Chem. Soc. Jpn. 1996, 69, 1403–1407.
15. Banerji, K. K.; Kothari, S. J. Chem. Research (M) 1999, 2118–2135.
16. Milovanovic, J. N.; Vasojevic, M. J. Chem. Soc., Perkin Trans. 2 1988, 533–535.
17. Mayanna, S. M.; Uma, K. V. Int. J. Chem. Kinet. 1980, 12, 861–870.
18. In a typical preparation of 1, 0.581 g (4.03 mmol) of 5-nonanol and 0.234 g (2.08 mmol) chlorobenzene were dissolved in
10 mL of CH2Cl2 and cooled in an ice bath. Then 20 mL of bleach at pH 7.5 cooled in an ice bath was added dropwise. The
solution was stirred in the ice bath for 30 min. After washing two times with 10% aqueous sodium carbonate and drying over

2763
sodium sulfate, the organic layer was diluted to 10 mL with CH2Cl2. This stock solution of 1, analyzed by GC and iodometric
titration, was 0.35 M 1 and 0.023 M 5-nonanol. The solution was stable for several days at −78°C, but decomposed within
a few hours at room temperature. For the reactions in Table 2, 1.25 mL of the stock solution of 1 was diluted to 5.0 mL with
acetic acid and 0.70 mL water with or without added salts was added.
19. All of the faster reactions in Table 2 were at least 93% complete within 35 min.
20. Fonouni, H. E.; Krishnan, S.; Kuhn, D. G.; Hamilton, G. A. J. Am. Chem. Soc. 1983, 105, 7672–7676 reported the NaCl
concentration of bleach to be 1.2 M.