Electrochemically induced transformation of 4-halomethyl-4-methylcyclohexa- 2,5-dien-1-ones into 3,4-dimethylphenol

Article abstract of DOI:10.1134/S1070363209020169

Electrochemical behavior of 4-halomethyl-4-methylcyclohexa-2,5-dien-1-ones and 2,6-dibromo-4,4-dimethylcyclohexa-2,5-dien-1-one was studied. Reductive dehalogenation of cyclohexa-2,5-dien-1-ones having a halogen atom at the neopentyl-like carbon atom give

Full text of DOI:10.1134/S1070363209020169

ISSN 1070-3632, Russian Journal of General Chemistry, 2009, Vol. 79, No. 2, pp. 264–268. © Pleiades Publishing, Ltd., 2009.
Original Russian Text © G.V. Gavrilova, A.A. Moiseeva, E.K. Beloglazkina, A.A. Gavrilov, N.V. Zyk, 2009, published in Zhurnal Obshchei Khimii, 2009,
Vol. 79, No. 2, pp. 275–279.
Electrochemically Induced Transformation
of 4-Halomethyl-4-methylcyclohexa-2,5-dien-1-ones
into 3,4-Dimethylphenol
G. V. Gavrilova, A. A. Moiseeva, E. K. Beloglazkina, A. A. Gavrilov, and N. V. Zyk
Faculty of Chemistry, Moscow State University, Vorob’evy gory 1, Moscow, 119992 Russia
e-mail: moiseeva@org.chem.msu.ru; bel@org.chem.msu.ru
Received February 28, 2008
Abstract—Electrochemical behavior of 4-halomethyl-4-methylcyclohexa-2,5-dien-1-ones and 2,6-dibromo-
4
,4-dimethylcyclohexa-2,5-dien-1-one was studied. Reductive dehalogenation of cyclohexa-2,5-dien-1-ones
having a halogen atom at the neopentyl-like carbon atom gives the corresponding carbanion which undergoes
anionic cyclopropyl–allyl rearrangement with subsequent addition of proton to form 3,4-dimethylphenol.
DOI: 10.1134/S1070363209020169
Cyclohexadienones and their analogs are
polyfunctional organic compounds that are capable of
reduction of 4-halomethyl-4-methylcyclohexa-2,5-dien-
1-ones at a glassy carbon electrode in DMF.
undergoing
various
chemical
transformations.
We previously examined electrochemical behavior
of a number of halogen-substituted cyclohexadienones
Introduction of halogen atoms into their molecules
considerably enhances their synthetic potential, and
such derivatives can be modified with the use of not
only traditional reagents but also enzymes, as well as
by the action of electric current. It is known [1–3] that
anions derived from diethyl malonate and diethyl 3-
oxopentanedioate are capable of adding at activated
unsaturated carbon–carbon bond in dienones according
to Michael. The mold fungus Aspergillus niger
promotes successive reductive dechlorination of the
[
7] and found that reductive dehalogenation of 2-
bromo-5-dibromomethyl-4-dichloromethyl-4-methyl-
cyclohexa-2,5-dien-1-one involves primarily elimina-
tion of the allylic bromine atoms. Next follows
elimination of the vinylic bromine in position 2, and
the final step is dehalogenation of the dichloromethyl
group. Elimination of the allylic and vinylic bromine
atoms occurs in a stepwise mode: in each step one
halogen atom is abstracted with simultaneous addition
of two electrons and subsequent protonation of inter-
CHCl fragment in trans-4-dichloromethyl-4-methyl-
2
3
-methylidene-3a,7a-dihydro-1-benzofuran-2,7-(3H,4H)-
dione due to the presence of iron-containing enzymes
4]. Analogous process is promoted by Bacillus mycoides
and Pseudomonas fluorescens [5]. 11β,21-Diacetoxy-
α-bromo-17α-hydroxypregna-1,4-diene-3,20-dione
+
mediate carbanion (+2e⎯, +H ). Geminal neopentyl-
idene halides undergo two-electron reductive
elimination without proton addition; in this case,
carbene-like species is formed as intermediate, and its
attack on the cyclohexadienone fragment results in
ring expansion and formation of tropones [7].
[
9
undergoes chromium(II) chloride-catalyzed transforma-
tion into 11β,21-diacetoxy-17α-hydroxy-5,9-cyclopregn-
In the present work we examined electrochemical
reduction of 4-chloromethyl-4-methylcyclohexa-2,5-
dien-1-one (I), 4-bromomethyl-4-methylcyclohexa-
1
-ene-3,20-dione. Heating of the latter in boiling
aqueous dioxane in the presence of trace amounts of an
acid or alkali leads to opening of the cyclopropane ring
with regeneration of the initial dienone [6].
2
,5-dien-1-one (II), and 2,6-dibromo-4,4-dimethyl-
cyclohexa-2,5-dien-1-one (III) in DMF in the presence
In the present work we found that the above reac-
tion sequence, i.e., reduction of the carbon–halogen
bond, intramolecular cyclopropanation, and cyclopro-
pane ring opening, is also typical of electrochemical
of Bu NClO using cyclic voltammetry (CV) at a
4
4
glassy carbon electrode and rotating disk electrode
(RDE) technique. The results are collected in table,
and cyclic voltammetry curves are shown in Figs. 1
264

ELECTROCHEMICALLY INDUCED TRANSFORMATION
265
(
(
a)
(a)
5
μA
5
μA
1
2
(
(
b)
c)
b)
1
.5 1.0 0.5 0.0 –0.5 –1.0 –1.5 –2.0 E/V
Fig. 1. Cyclic voltammograms of (a) 2,6-dibromo-4,4-
dimethylcyclohexa-2,5-dien-1-one (III) and (b) (1) 2-bromo-
4
,4-dimethylcyclohexa-2,5-dien-1-one (V) and (2) 4,4-di-
–3
methylcyclohexa-2,5-dien-1-one (VI); concentration 10 M,
glassy carbon electrode, DMF, 0.1 M Bu NClO
4
4
.
1
.0
0.0
–1.0
–2.0
E/V
Fig. 2. Cyclic voltammograms of (a) 3,4-dimethylphenol
(
(
IV), (b) 4-chloromethyl-4-methylcyclohexa-2,5-dien-1-one
and 2. None of the examined compounds (I–III) was
oxidized at a glassy electrode under the given condi-
tions, so that we were able to follow the formation of
halide ions by their reoxidation peaks upon reversal of
the potential after the corresponding cathodic peaks.
Compounds I–III displayed only two-electron reduc-
tion steps corresponding to elimination of halogen
atoms.
I), and (c) 4-bromomethyl-4-methylcyclohexa-2,5-dien-1-
–3
one (II); concentration 10 M, glassy carbon electrode,
DMF, 0.1 M Bu NClO .
4 4
Scheme 1) since no peak corresponding to reduction of
dienone VI is observed on the CV curve. In the course
of reverse potential scans, compounds I and II showed
reoxidation peak on the cathodic branch, which
completely coincided with the oxidation peak of 3,4-
dimethylphenol (IV). We found that the latter is not
reduced under the given conditions. Figure 2 shows
that the CV curves for cyclohexadienones I and II,
excluding the peaks corresponding to reductive elimina-
tion of halide ion, almost completely coincide with the
curves obtained for 3,4-dimethylphenol (IV).
Cyclic voltammetry of solutions of dibromo deriv-
ative III showed two peaks on the cathodic branch,
resulting from stepwise elimination of two halogen
atoms, and the reversible peak corresponding to the
reduction of 4,4-dimethylcyclohexa-2,5-dien-1-one
(
VI) to stable radical anion VII (Scheme 1, Fig. 1).
Obviously, as we showed previously for analogous
monobromo derivative [7], electrochemical reduction
of compounds containing two halogen atoms) gives
rise to reversible peak corresponding to the formation
of radical anion VII provided that VI is formed as
intermediate (Fig. 1).
Reduction potentials of compounds I–III according to the
cyclic voltammetry data; Ag/AgCl/KCl (sat.), glassy carbon
electrode, DMF, 0.05 M Bu
a
4
NClO
4
as supporting electrolyte
Comp. no.
E
cp, V
E1/2, V
The CV curves obtained for solutions of
cyclohexadienones I and II having one halomethyl
groups revealed only one reduction peak due to elimina-
tion of halide ion: upon reversal of the potential
b
c
c
I
–1.66/1.18 ; 1.24
–1.65 (2)
–1.55 (2)
d
II
–1.56/0.83 ; 1.24
d
d
–
–
1.37/0.84 ; –1.60/0.84 ;
1.92/–1.82
III
–1.36 (2); –1.65 (2)
reoxidation peak of chloride (E = 1.18 V) or bromide
ap
a
–1
ion (E = 0.83 V), respectively, was observed in the
E
cp is the cathodic peak potential (200 mV s )/reverse peak
ap
potential; E1/2 is the half-wave potential measured at a rotating
disk electrode (2800 rpm); the number of electrons determined
by comparing with the one-electron oxidation wave of ferrocene
is given in parentheses. Reoxidation of chloride ion. Reoxida-
tion of newly formed 3,4-dimethylphenol (IV) (irreversible
anodic region after the reduction peak (Fig. 2). Ob-
viously, carbanion A generated by reductive dehalogena-
tion is not converted into cyclohexadienone VI (pro-
duct of two-step reduction of dibromoketone III
through intermediate monobromo derivative V; see
b
c
d
oxidation potential Eap = 1.22 V). Reoxidation of bromide ion.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 79 No. 2 2009

2
66
GAVRILOVA et al.
OH
O
H
H
Me
Me
VIII
IX
+
H+
O
O
O −
OH
+H+
+
Hlg−
2e
2
−
H
Me
1
Me
CH Hlg
Me
CH2−
Me
3
2
Me
I, II
А
B
IV
+
H+
O
O
O
O−
Br
Br
Br
−
+
−
+
+
2e, −Br , +H
+2e, −Br , +H
+e
−e
(
−1.37 V )
(−1.60 V )
Me
Me
Me
Me
Me
Me
Me
Me
III
V
VI
VII
Hlg = Cl (I), Br (II).
1
2
1
3
2
3
Thus the results of our electrochemical study on 4-
structure (Fig. 3) where the C –C , C –C , and C –C
methyl-4-halomethylcyclohexa-2,5-dien-1-ones I and
II showed that their electrochemical reduction in DMF
at a glassy electrode leads to the formation of 3,4-
dimethylphenol (IV). This was also confirmed by
studying the behavior of compounds I and II in the
presence of phenol IV. Neither “doubling” nor change
of the reoxidation peak shape (as compared to
electrochemical reduction of individual compounds I
and II) was observed on the CV curves upon reversal
of the potential in the cathodic region. These findings
suggest that the system contains no oxidizable
compounds other than phenol IV.
distances are 1.525, 1.511, and 1.515 Å, respectively. It
is interesting that the rate of the transformation A → B
is higher than the rate of possible protonation of
intermediate A, which could give rise to dienone VI
(cf. the data for other halogen-substituted cyclohexadi-
enones [7]).
Examples of anionic cyclopropylcarbinyl–homo-
allyl rearrangement have been reported [6, 8]. In our
case, the isomerization process is favored by the
presence of conjugated carbonyl group in the substrate
molecule [9], as well as by the formation of
energetically favorable aromatic structure IV. Accord-
ing to the calculations, the heat of formation of phen-
Presumably, initial two-electron reduction with
elimination of halide ion from compound I or II gives
carbanion A which undergoes intramolecular Michael
addition at the β-carbon atom in the dienone system.
Protonation of bicyclo[4.2.0]heptadienone anion B
thus formed yields phenol IV. The possibility for
formation of intermediate B follows from the results of
semiempirical quantum-chemical calculations, accord-
ing to which the optimized geometry of the anion [I –
–
–1
oxide ion [IV – H] is lower by 43.4 kcal mol than
–1
that found for anion B (–62.14 and –19.54 kcal mol ,
respectively). Alternative pathway involving protona-
tion of anion B with conservation of the bicyclo[4.2.0]-
heptadienone structure should be ruled out, for dienol
VIII isomeric to IV should undergo tautomerization
into enone IX, while the latter cannot be
electrochemically inert. In addition, electrochemical
oxidation of enone IX should occur at a potential value
–
Cl] corresponds to just bicyclo[4.2.0]heptadienone
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 79 No. 2 2009

ELECTROCHEMICALLY INDUCED TRANSFORMATION
267
of higher than 1.5 V rather than at E = 1.24 V typical
ra
(a)
of phenol [10].
Thus we have shown that the behavior of halogen-
containing cyclohexadienones under electrochemical
reduction conditions is determined by the position of
halogen atom in the substrate molecule. If vinyl- or
allyl-type halogen atom (or atoms) is present, the
process occurs as successive reductive dehalogenation
with conservation of the cyclohexadienone fragment
[
7]. If the substrate molecule contains a halo- or
dihalomethyl group attached to tertiary ring carbon
atom, the reduction process is also accompanied by
dehalogenation, but the cyclohexadiene fragment is
transformed into cycloheptatrienone (dihalo deriv-
atives) [7] or phenol (one halogen atom).
(b)
–
0.598
0.332
EXPERIMENTAL
0
.074
1
13
The H and C NMR spectra were measured at 25°C
0
.105
–
0.137
0.158
0.067
from solutions in CDCl on a Varian VXR-400 spec-
3
–
0.593
trometer using tetramethylsilane as internal reference.
The IR spectra were recorded on a UR-20 instrument
from samples dispersed in mineral oil. The UV spectra
were obtained on a Specord M-40 spectro-photometer
from solutions in ethanol.
–
0
.075
–
0.119
0
.026
0.078
–0.219
0.043
–
0.052
0.018 0.019
Fig. 3. (a) Optimized structure of anion [I – Cl] and
Electrochemical studies were performed using a PI-
5
0-1.1 potentiostat coupled with a PR-8 prog-rammer.
0.045
–
A glassy carbon electrode (d = 2 mm) was used as
working electrode, supporting electrolyte was a 0.1 M
solution of Bu NClO in DMF, reference electrode was
(
b) distribution of charge density therein.
4
4
a silver chloride electrode [Ag/AgCl/KCl (sat.)], and a
platinum plate served as auxiliary electrode. The
tion metals and some second- and third-row metals.
The geometric parameters were optimized with a con-
vergence gradient of no larger than 10 cal Å mol .
–3
substrate concentration was 10
M. In cyclic
–
1
–1
voltammetry experiments, the potential scan rate was
–1
–1
2
00 mV s , and in RDE experiments, 20 mV s . The
2-Bromo-4,4-dimethylcyclohexadien-1-one
and 4,4-dimethylcyclohexa-2,5-dien-1-one [13] were
synthesized according to known procedures.
[12]
potentials are given with account taken of iR
compensation. The number of electrons transferred in
redox processes was determined by comparing the
wave limiting current in RDE experiments with the
one-electron oxidation current of ferrocene taken at the
same concentration.
4
-Chloromethyl-4-methylcyclohexa-2,5-dien-1-
one (I) was synthesized according to the procedure
described in [14]. UV spectrum: λ 233 nm (logε
max
–1
1
3
.84). IR spectrum, ν, cm : 1630, 1660. H NMR
All measurements were performed under dry argon;
samples were dissolved in preliminarily degassed
solvent. Dimethylformamide of pure grade was stirred
over freshly calcined potassium car-bonate over 4 days
and distilled under reduced pres-sure first over P O
spectrum, δ, ppm: 1.35 s (3H, 4-Me), 3.54 s (2H, 4-
3
CH ), 6.34 d (2H, 2-H, 6-H, J = 9.8 Hz), 6.83 d (2H,
2
3
13
1
3-H, 5-H, J = 9.8 Hz). C–{ H} NMR spectrum, δ ,
ppm: 23.09 (4-Me), 42.42 (C ), 63.91 (4-CH Cl),
104.21 (C , C ), 129.87 (C , C ), 152.05 (C=O).
C
4
2
2
6
3
5
2
5
and then over anhydrous CuSO4.
Found, %: C 61.59; H 5.55. C
C 61.73; H 5.75.
8 9
H ClO. Calculated, %:
Quantum-chemical calculations were performed us-
ing semiempirical SCF PM3 approximation [11] exten-
ded via inclusion of parameters of all first-row transi-
4-Bromomethyl-4-methylcyclohexa-2,5-dien-1-
one (II). The UV, IR, and mass spectra of II were
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 79 No. 2 2009

2
68
GAVRILOVA et al.
1
consistent with those reported in [14]. H NMR
Chem. Soc., 2000, vol. 65, no. 2, p. 103.
spectrum, δ, ppm: 1.36 s (3H, 4-Me), 3.41 s (2H, 4-
6. Rakhit, S. and Gut, M., J. Am. Chem. Soc., 1964, vol. 86,
3
CH Br), 6.32 d (2H, 2-H, 6-H, J = 9.7 Hz), 6.81 d
no. 7, p. 1432.
2
3
13
1
(
2H, 3-H, 5-H, J = 9.7 Hz). C–{ H} NMR spectrum,
δ , ppm: 24.26 (4-Me), 41.55 (C ), 63.89 (4-CH Br),
04.23 (C , C ), 129.77 (C , C ), 152.18 (C=O).
7
. Gavrilova, G.V., Moiseeva, A.A., Beloglazkina, E.K.,
Gavrilov, A.A., and Butin, K.P., Izv. Ross. Akad. Nauk,
Ser. Khim., 2006, no. 9, p.1558; Russ. Chem. Bull.,
4
C
2
2
6
3
5
1
2
006, vol. 55, no. 9, p. 1617.
2
,6-Dibromo-4,4-dimethylcyclohexa-2,5-dien-1-
8
9
. Stork, G. and Tsuji, J., J. Am. Chem. Soc., 1961, vol. 83,
no. 12, p. 2783.
one (III). The UV, IR, and mass spectra of III were
1
consistent with those reported in [15]. H NMR
. Reutov, O.A., Kurts, A.L., and Butin, K.P., Organi-
cheskaya khimiya (Organic Chemistry), Moscow:
Binom, 2004, vol. 4, p. 273.
spectrum, δ, ppm: 1.32 s (6H, 4-Me), 7.28 s (2H, 3-H,
1
3
1
5
-H). C–{ H} NMR spectrum, δ , ppm: 26.10 (4-
C
4
2
6
3
5
Me), 44.06 (C ), 120.48 (C , C ), 156.64 (C , C ),
72.42 (C=O).
10. Organic Electrochemistry: An Introduction and a Guide,
1
Baizer, M.M., Ed., New York: Marcel Dekker, 1973.
1
1. Gavrilova, G.V., Gavrilov, A.A., Krut’ko, D.P., and Bu-
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