Electrochemically induced Favorsky rearrangement of alkyl benzyl ketones

Article abstract of DOI:10.1023/A:1022481306531

Electrolysis of alkyl benzyl ketones in MeOH in an undivided electrolyzer in the presence of the Nal-NaOH mediator system induces the process similar to the Favorsky rearrangement to produce arylalkanecarboxylates in 80-90% yield (per substance) and with the 50-55% current efficiency.

Full text of DOI:10.1023/A:1022481306531

228
Russian Chemical Bulletin, International Edition, Vol. 52, No. 1, pp. 228—231, January, 2003
Electrochemically induced Favorsky rearrangement of alkyl benzyl ketones
M. N. Elinson,ꢀ S. K. Feducovich, A. S. Dorofeev, A. N. Vereshchagin, and G. I. Nikishin
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
47 Leninsky prosp., 119991 Moscow, Russian Federation.
Fax: +7 (095) 135 5328. Еꢀmail: elinson@ioc.ac.ru
Electrolysis of alkyl benzyl ketones in MeOH in an undivided electrolyzer in the presence
of the NaI—NaOH mediator system induces the process similar to the Favorsky rearrangement
to produce arylalkanecarboxylates in 80—90% yield (per substance) and with the 50—55%
current efficiency.
Key words: electrolysis, electrochemical oxidation, alkyl benzyl ketones, mediators, meꢀ
diator systems, arylalkanecarboxylates.
Ketone oxidation reactions are used to obtain carbꢀ
and αꢀhydroxyketals formed in significant amounts along
with esters.15
oxylic acids and their derivatives.1 The haloform reaction
is the simplest method for the preparation of carboxylic
acids or esters from methyl ketones.2,3 This method is
especially significant in syntheses of aromatic carboxylic
acids due to a much greater easiness of introduction of the
acetyl group into the aromatic ring compared to the inꢀ
troduction of the carboxylic group.4
The twoꢀcomponent NaI—NaOH mediator system
was also successfully used for the electrooxidation of cyꢀ
clic ketones.16,17 The recent use of this system made it
possible to substantially improve the electrochemical
oxidation of alkyl aryl ketones to the corresponding
αꢀhydroxyketals.18
A sharp increase in studies on the electrochemistry of
organic compounds in the last decades allowed electroꢀ
synthesis to become a competitive method of the modern
organic chemistry.5,6
However, the electrochemical oxidation of ketones
was highly selective only in particular cases.
The direct oxidation of ketones produces a mixture of
saturated and unsaturated hydrocarbons, carbon oxide and
dioxide.7—10
The purpose of the present study was to use an alkali
metal iodide—metal hydroxide system for the enhanceꢀ
ment of the efficiency and selectivity of the electrochemiꢀ
cal oxidation of alkyl benzyl ketones 1а—e to methyl
esters 2а—e (Scheme 1, Table 1).
The electrooxidation in MeCN or TFA results in the
nonselective remote functionalization of ketones due to
the subsequent transformations and decomposition of the
Scheme 1
primarily formed radical cations R1R2C=O•+ 11,12
.
In some oxidative transformations of ketones by methꢀ
ods of the classical organic chemistry, such as the haloform
reaction, the preliminary αꢀhalogenation of ketones is the
key step.13
This step is a part of the overall process of electroꢀ
chemical ketone oxidation in the presence of halide as a
mediator in the system. Under such conditions, the
electrocatalytic variant of the haloform reaction occurs:
alkyl methyl and aryl methyl ketones are transformed into
carboxylates.14
M = Na, K
Hal = Br, I
Cyclohexanone and alkyl aryl ketones were electroꢀ
oxidized to the corresponding αꢀhydroxyketals using broꢀ
mides as mediators.15 The electrooxidation of alkyl benꢀ
zyl ketones in MeOH produced arylalkanecarboxylates.
However, the latter reaction was insufficiently selective,
a: R1 = R2 = R3 = H; b: R1 = R2 = H, R3 = Me; c: R1 = R3 = H,
R
2 = Me; d: R1 = MeO, R2 = R3 = H; e: R1 = Cl, R2 = R3 = H
As mentioned above, the electrooxidation of alkyl
methyl and aryl methyl ketones in MeOH in the presence
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 216—219, January, 2003.
1066ꢀ5285/03/5201ꢀ228 $25.00 © 2003 Plenum Publishing Corporation

Favorsky rearrangement of alkyl benzyl ketones
Russ.Chem.Bull., Int.Ed., Vol. 52, No. 1, January, 2003
229
Table 1. Electrooxidation of alkyl benzyl ketones 1a—ea
Scheme 2
Entry Keꢀ Mediaꢀ
Metal
hydroxide
Amount of
electricity
/F mol–1
Yieldb
(%)
tone
tor
1
1a
1a
1a
1a
1a
1a
1b
1c
1d
1e
NaBr
NaI
NaBr
NaI
NaI
KI
NaI
NaI
NaI
NaI
—
—
7.0
6.0
4.5
3.2
3.2
3.2
3.2
3.2
3.2
3.2
2a, 61 (17)
2a, 69 (23)
2a, 71 (32)
2a, 88 (55)
2a, 81 (51)
2a, 86 (54)
2b, 87 (54)
2c, 85 (53)
2d, 79 (49)
2e, 83 (52)
2
3
4
5
6
7
8
9
NaOH
NaOH
NaOH c
KOH
NaOH
NaOH
NaOH
NaOH
cal oxidation of cyclohexanone16,17 and alkyl aryl keꢀ
tones18 in the presence of halides as mediators, we proꢀ
posed the mechanism of electrochemical rearrangement of
alkyl benzyl ketones 1a—e to arylalkylcarboxylates 2a—e.
The reactions on electrodes, which occur during the
electrochemical transformation of 1a—e into arylalkylꢀ
carboxylates 2a—e, are usual for the mediator system used
and involve the formation of halogen on the anode and
hydrogen release on the cathode with the generation of
the methoxide ions
10
a Ketone (15 mmol), mediator (10 mmol), alkali (2 mmol) in
MeOH (20 mL), Fe cathode, C anode, undivided electrolyzer,
30 °C; conversion of 1a—e is 98—100%.
b The yield per substance according to the 1H NMR spectroꢀ
scopic data; the current efficiency (%) is given in parentheses.
c NaOH (5 mmol).
of alkali metal bromides in an undivided electrolyzer reꢀ
sults in the electrocatalytic variant of the haloform reacꢀ
tion producing methyl carboxylates in which the number
of carbon atoms in the hydrocarbon chain is by one atom
less than that in the starting ketones.14
Anode:
2 Hal– – 2 e
Hal2,
2 MeO– + H2,
Cathode: 2 MeOH + 2 e
Hal = I, Br.
Then the αꢀhalogenation of ketones 1a—e occurs in a
solution, as it has previously been established for alkyl
aryl ketones, to form intermediate αꢀhaloketones of two
types: А and B (Scheme 3).
The electrolysis of alkyl benzyl ketone 1а under simiꢀ
lar conditions gave methyl 3ꢀphenylpropionate (2a) in
61% yield and with the 17% current efficiency (Table 1,
entry 1). Thus, the electrolysis of 1а in the presence of
NaBr also affords methyl carboxylate but the number of
carbon atoms in the hydrocarbon chain remains unꢀ
changed. This process is analogous to the Favorsky rearꢀ
rangement with the only difference that ketone instead of
haloketone (as in the chemical variant of the Favorsky
rearrangement) is used as the initial compound and byꢀ
product 3а forms in 32% yield (Scheme 2).
The use of the NaI mediator increases the yield and
efficiency of 2а to 69 and 23%, respectively. The use of
the NaBr—NaOH and NaI—NaOH mediator systems (enꢀ
tries 3 and 4) further enhances the yields of 2а. Under the
optimal conditions using the NaI—NaOH mediator sysꢀ
tem, ester 2a was obtained in 88% yield and with the 55%
efficiency (entry 4); byꢀproduct 3а formed in ∼6% yield.
Ketones 1b—e were transformed into esters 2b—e in
79—88% yields and with the ∼50% efficiency under the
conditions optimal for the transformation of ketone 1a
into ester 2a.
Under the action of the methoxide ion, haloketone А
undergoes intramolecular cyclization to intermediate
cyclopropanone, whose opening produces ester 2 accordꢀ
ing to the Favorsky rearrangement mechanism. The fact
that only one transformation route occurs for haloketone
А is most probably caused by the presence of an acidic
benzyl proton in this ketone. Haloketone В is characterꢀ
ized by two reaction routes. One of them is similar to the
transformation of haloketone А and also results in the
formation of ester 2. However, since the benzyl proton is
absent, haloketone В is capable of the second reaction
route: addition of the methoxide ion to the carbonyl group
followed by intramolecular cyclization to intermediate
epoxide and its opening, under the electrolysis condiꢀ
tions, to form αꢀhydroxyketal 3.
Similar transformations affording αꢀhydroxyketals
have previously been observed in the electrolysis of cycloꢀ
hexanone16,17 and alkyl aryl ketones18 in the presence of
halides.
The addition of NaOH has a substantial effect on the
process. First, its overall efficiency enhances because the
complete conversion of the initial ketone is achieved when
a smaller amount of electricity is passed. A similar result
Based on the obtained results and taking into account
the previously considered mechanisms of electrochemiꢀ

230
Russ.Chem.Bull., Int.Ed., Vol. 52, No. 1, January, 2003
Elinson et al.
Scheme 3
has earlier18 been observed for the electrochemical oxidaꢀ
tion of alkyl aryl ketones to the corresponding αꢀhydroxyꢀ
ketals and is probably caused by two factors: (1) introꢀ
duction of NaOH increases the concentration of the
methoxide ions in the solution and, thus, all processes
involving the methoxide ions are accelerated and (2) inꢀ
troduction of NaOH increases the current concentration
of the enolic form of ketone, thus accelerating the haloꢀ
genation of the initial ketone. The combined effect of
these two factors enhances the overall efficiency of
electrooxidation of initial ketones 1a—e. Second, the inꢀ
troduction of NaOH changes the ratio of ester 2 to
αꢀhydroxyketal 3 toward an increase in the amount of
ester 2. The latter is most likely due to the fact that the
most part of haloketone B is transformed into ester 2 in
the presence of NaOH. We cannot exclude the influence
of the NaOH additive on the ratio of haloketones formed
in the halogenation step and the mutual transformation of
haloketones А and В in the presence of NaOH (Scheme 4).
Halogen 1,3ꢀmigration in haloenol С occurs, most
likely, according to the principles characteristic of the
known fast allyl rearrangement.19 (Halogen 1,3ꢀmigraꢀ
tion has previously been mentioned in the rearrangement
of α,αꢀdibromoketones to α,α´ꢀdibromoketones.20)
Scheme 4

Favorsky rearrangement of alkyl benzyl ketones
Russ.Chem.Bull., Int.Ed., Vol. 52, No. 1, January, 2003
231
1H NMR, δ: 2.68 (t, 2 H, CH2, J = 7 Hz); 2.98 (t, 2 H, CH2,
J = 7 Hz); 3.70 (s, 3 H, OMe); 7.31 (m, 4 H, Ar).
Thus, the process similar to the Favorsky rearrangeꢀ
ment was carried out in an undivided electrolyzer during
the electrolysis of methanolic solutions of alkyl benzyl
ketones 1a—e in the presence of the mediator.
This process is a convenient and economic method
for the direct transformation of alkyl benzyl ketones into
the corresponding esters of arylalkanoic acids in the presꢀ
ence of the NaI—NaOH mediator system. The process
uses standard and readily available reagents, inexpensive
equipment, and an undivided electrolyzer. The proceꢀ
dures of electrolysis and isolation of final compounds are
simple and convenient to use in both laboratory setups
and larger (pilot or industrial) installations.
2,2ꢀDimethoxyꢀ1ꢀphenylpropanꢀ1ꢀol (3) was isolated by crysꢀ
tallization from the reaction mixture (see Table 1, entry 1,
ether—hexane, 1 : 1) in 21% yield, m.p. 59—61 °C (cf. Ref. 25:
m.p. 63—65 °C). 1H NMR, δ: 1.05 (s, 3 H, Me); 2.73 (s, 1 H,
ОН); 3.24 (s, 3 H, OMe); 3.33 (s, 3 H, OMe); 4.80 (s, 1 Н, CH);
7.10—7.55 (m, 5 H, Ar).
This work was financially supported by the Russian
Foundation for Basic Research (Project No. 00ꢀ03ꢀ
32913a) and the Foundation for Leading Scientific
Schools (Project No. 00ꢀ15ꢀ97328).
References
Experimental
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1
Н NMR spectra were recorded on Bruker WMꢀ250 and
Bruker AMꢀ300 instruments with working frequencies of 250
and 300 MHz, respectively, in CDCl3. Chemical shifts in the
NMR spectra were presented in the δ scale relatively to Me4Si.
GLC analysis was carried out on an LKhMꢀ80 chromatoꢀ
graph with a flameꢀionization detector using nitrogen as carrier
gas with a rate of 30 mL min–1 (column (glass) 2500×3 mm with
5% SEꢀSuperphase on Super Inerton (0.16—0.20 mm)) to moniꢀ
tor the conversion of initial ketones 1a—e.
7. W. E. Bradt and N. J. Opp, Trans. Electrochem. Soc., 1931,
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The initial ketones were commercial reagents (Reakhim and
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8. M. Yokoyama, Bull. Chem. Soc. Jpn., 1933, 8, 71.
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Electrolysis (general procedure). A solution of ketone
(15 mmol), mediator (10 mmol), and alkali (2 mmol) in MeOH
(20 mL) was electrolyzed in an undivided cell equipped with a C
anode and a Fe cathode (surface area of the electrodes was
5 cm2) at 30 °C and a constant current density of 100 mA cm–2
passing a specified amount of electricity through the solution
(see Table 1). The reaction mixture was neutralized with dilute
HCl, and the solvent was evaporated. The mixture was extracted
with Et2O. The extract was washed with an aqueous solution of
Na2S2O3 and water and dried over Na2SO4. The ether was disꢀ
tilled off, and the residue was analyzed by 1H NMR spectrosꢀ
copy. Esters 2а—е were isolated by distillation.
Methyl 3ꢀphenylpropionate (2a), 79% yield, b.p. 122—124 °C
(14 Torr) (cf. Ref. 22: b.p. 68—70 °C (2 Torr)). 1H NMR, δ:
2.67 (t, 2 H, CH2, J = 7 Hz); 2.99 (t, 2 H, CH2, J = 7 Hz); 3.70
(s, 3 H, OMe); 7.28 (m, 5 H, C6H5).
Methyl 2ꢀmethylꢀ3ꢀphenylpropionate (2b), 78% yield, b.p.
59—60 °C (0.7 Torr) (cf. Ref. 23: b.p. 90—93 °C (1 Torr)).
1H NMR, δ: 1.15 (d, 3 H, Me, J = 7 Hz); 2.66 (m, 2 H, CH2);
2.99 (m, 1 H, CH); 3.63 (s, 3 H, OMe); 7.28 (m, 5 H, Ar).
Methyl 3ꢀphenylbutanoate (2c), 76% yield, b.p. 130—132 °C
(45 Torr) (cf. Ref. 24: b.p. 74—78 °C (0.5 Torr)). 1H NMR, δ:
1.32 (d, 3 H, Me, J = 7 Hz); 2.62 (m, 2 H, CH2); 3.31 (m, 1 H,
CH); 3.67 (s, 3H, OMe); 7.28 (m, 5 H, C6H5).
Methyl 3ꢀ(4ꢀmethoxyphenyl)propionate (2d), 71% yield, b.p.
148—150 °C (14 Torr), m.p. 36—37 °C (petroleum ether) (cf.
Ref. 22: b.p. 35—36 °C). 1H NMR, δ: 2.66 (t, 2 H, CH2,
J = 7 Hz); 2.93 (t, 2 H, CH2, J = 7 Hz); 3.68 (s, 3 H, OMe); 3.81
(s, 3 H, OMe); 7.02 (d, 2 H, Ar, J = 8 Hz); 7.14 (d, 2 H, Ar,
J = 8 Hz).
24. H. O. House and M. J. Umen, J. Org. Chem., 1973, 38, 3893.
25. W. D. McPhee and E. Klingsberg, J. Am. Chem. Soc., 1944,
66, 1132.
Methyl 3ꢀ(4ꢀchlorophenyl)propionate (2e), 72% yield, b.p.
136—138 °C (14 Torr) (cf. Ref. 22: b.p. 85—86 °C (2 Torr)).
Received May 23, 2002