First synthesis of 1-aryl-4,4-dichlorobut-3-en-1-ones. The electrochemical reduction of 1-aryl-4,4,4-trichlorobut-2-en-1-ones as a key step

Article abstract of DOI:10.1016/j.tet.2006.11.054

The first method for the synthesis of 1-aryl-4,4-dichlorobut-3-en-1-ones is reported. Treatment of acetophenones with anhydrous chloral leads to 1-aryl-4,4,4-trichloro-3-hydroxybutan-1-ones in near quantitative yields. These compounds were efficiently deh

Full text of DOI:10.1016/j.tet.2006.11.054

Tetrahedron 63 (2007) 1175–1182
First synthesis of 1-aryl-4,4-dichlorobut-3-en-1-ones. The
electrochemical reduction of 1-aryl-4,4,4-trichlorobut-
2-en-1-ones as a key step
a
a
a
b,
Antonio Guirado,a, Bruno Martiz, Raquel Andreu, Delia Bautista and Jesus Galvez
*
*
ꢀ
ꢀ
aDepartamento de Quꢀımica Orgaꢀnica, Facultad de Quꢀımica, Universidad de Murcia, Campus de Espinardo,
30071 Murcia, Apartado 4021, Spain
bDepartamento de Quꢀımica Fꢀısica, Facultad de Quꢀımica, Universidad de Murcia, Campus de Espinardo,
30071 Murcia, Apartado 4021, Spain
Received 27 September 2006; revised 15 November 2006; accepted 20 November 2006
Available online 15 December 2006
Abstract—The first method for the synthesis of 1-aryl-4,4-dichlorobut-3-en-1-ones is reported. Treatment of acetophenones with anhydrous
chloral leads to 1-aryl-4,4,4-trichloro-3-hydroxybutan-1-ones in near quantitative yields. These compounds were efficiently dehydrated with
either sulfuric or p-toluenesulfonic acid to give 1-aryl-4,4,4-trichlorobut-2-en-1-ones, which were selectively converted to the title compounds
in fair to quantitative yields by electrochemical reduction. The X-ray crystallographic structure of 4,4-dichloro-1-(4-methoxyphenyl)but-3-
en-1-one has been determined. The preferential formation of b,g-unsaturated ketones with total exclusion of the corresponding a,b-unsatu-
rated isomers has been discussed with the aid of HF and B3LYP density functional theory methods.
Ó 2006 Elsevier Ltd. All rights reserved.
1. Introduction
preparing new heterocyclic compounds and synthetic inter-
mediates of significant interest.7
The synthesis of b,g-unsaturated ketones has received
considerable attention since these have significant synthetic
utility.1 Owing to a notable proclivity of these compounds to
undergo isomerization towards conjugated a,b-unsaturated
isomers,2 mild experimental conditions and exclusion of
strong acidic or basic catalysts are considered essential
factors in developing fine preparative methods on this topic.
The most usual synthetic procedures for b,g-unsaturated ke-
tones include acylation of allylic organometallics of a variety
of elements,2,3 whereas reaction between aldehydes and
some of these organometallic compounds followed by oxi-
dation of the corresponding allyl alcohols is also an exploit-
able preparative process.4 Some other less general reactions
yielding b,g-unsaturated ketones have also been described.5
As a further result of working on this project, we recently
communicated the first synthesis of 3-aryl-5-dichloro-
methyl-2-pyrazolines based on using 1-aryl-4,4-dichloro-
but-3-en-1-ones 5 as key intermediates.8 We have also
found that 5 are able to provide novel 5-dichloromethylisox-
azolines in good yields.9 In these cases compounds 5 exhibit
a chemical behaviour of a significant preparative interest
since reactions with dinucleophilic agents can promote
cyclization processes associated with a simultaneous gener-
ation of dichloromethyl groups. In this manner, pre-chlori-
nated synthons derived from chloral are highly effective in
overcoming severe obstacles of chemical incompatibility
caused by the indiscriminate action of the reagents most
used to generate dichloromethyl groups.10
Chloral is an inexpensive multipurpose starting material for
organic synthesis.6 Direct reactions of chloral with certain
compounds can provide derivatives bearing a trichloro-
methyl group of a high electrosynthetic potential. In this re-
action we recognized the starting point of different routes for
Given the synthetic interest of compounds 5, we now report
full details of this highly efficient synthetic approach as well
as spectral and X-ray crystallographic structural data for this
class of substances.
An optimal reaction route for preparing products 5 has been
established through a sequence of chemical and electro-
chemical steps, as shown in Scheme 1. Preparations of chloral-
Keywords: Electrosynthesis; Reduction; Dechlorination; Chloral; b,g-
Unsaturated ketones.
* Corresponding authors. Tel.: +34 968367490; fax: +34 968364148;
e-mail: anguir@um.es
acetophenones
2 have been described by arylation
0040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.11.054

1176
A. Guirado et al. / Tetrahedron 63 (2007) 1175–1182
OH
O
O
O
-H2O
Cl3CCHO
Ar
CCl3
Ar
Ar
CCl3
1
2
3
2e -Cl
O
Cl
Ar
O
Cl
5
Cl
H
Ar
O
Cl
4
Cl
Ar
Cl
PhCOCl
-Cl
6
Entry
Ar
a
b
c
d
e
f
C6H5
PhCOO
Ar
4-F-C6H4
4-Cl-C6H4
4-Br-C6H4
4-Me-C6H4
4-MeOC6H4
4-NO2C6H4
2,4-Me2C6H3
4-Ph-C6H4
2-C10H7
Cl
Cl
7
g
h
i
j
Scheme 1.
processes involving ring opening of b-trichloromethyl-b-
propiolactones,11 and by reaction of chloral with acetophe-
none derivatives12 such as imines and trimethylsilyl enol
ethers. A few old examples of direct reactions between chlo-
ral and acetophenones yielding products 2 were reported13
but they omit fundamental details such as experimental con-
ditions, yields and physical and analytical properties for
these products. For this reason, precise preparative experi-
mental conditions and physical and analytical data for these
compounds have been included here as Supplementary data.
had successful results on the basis of highly selective elec-
trochemical reductions of intermediates 3.
In order to prepare 1-aryl-4,4,4-trichlorobut-2-en-1-ones 3,
chloralacetophenones 2 were dehydrated with either thionyl
chloride or phosphorus pentoxide. These reactions occurred
with moderate efficiency. Their results were compared with
those arising from dehydration promoted by acidic catalysis
with either sulfuric or p-toluenesulfonic acids. These other
processes, in general, were found to be much more efficient
but in some cases yields were found to be remarkably depen-
dent on the acidic reagent used. Results are given for the
most proficient acid to provide each of the compounds 3.
2. Results and discussion
Direct preparation of chloralacetophenones 2 was attempted
by reaction between acetophenones 1 and chloral hydrate but
these processes yielded small amounts of reaction products
that were isolated and identified as the desired compounds
2. However, much more efficient were the reactions with an-
hydrous chloral, which in general, provided fair to high
yields (70–89%). In order to attempt a straightforward gen-
eration of the targeted compounds 5 from compounds 2 they
were treated with zinc metal in hot acetic acid. The forma-
tion of 5 was found to be unsatisfactory due to a conjunction
of adverse factors such as the requirement of large excess of
reducing reagent, low yields, incompatibility with the pres-
ence of nitro groups and a remarkable difficulty in the isola-
tion and purification of products. It should also be noted that
the electrochemical reduction of compounds 2 failed com-
pletely, leading to the formation of complex mixtures of un-
identifiable products instead of products 5. In the search for
an effective method for preparing the desired compounds we
Cathodic reductions of solutions of compounds 3 in aceto-
nitrile–acetic acid–lithium perchlorate at a mercury pool
cathode were carried out under a constant potential. The
electricity consumption was always 2 F/mol of 3. At the
end of the electrolyses, the catholyte solutions were checked
by TLC and GC showing a complete transformation of start-
ing materials to single products, which were easily isolated
by evaporation of the solvent under reduced pressure, addi-
tion of the residue onto cold water and filtration of the
precipitated solid. Highly pure products were isolated in
this manner and were crystallized and identified by IR,
MS, high field NMR spectroscopy and microanalyses as
1-aryl-4,4-dichlorobut-3-en-1-ones 5. Yields were almost
quantitative. Advantageously, these results were found to
be reproducible by changing the cathodic material from mer-
cury to graphite. Advantageously, it has been established
that lithium perchlorate can be replaced by sodium tetra-
fluoroborate, leading to the same results. Worthy of note is

A. Guirado et al. / Tetrahedron 63 (2007) 1175–1182
1177
evidence for the generation of species 4 was established by
carrying out the cathodic reduction of 3d in the presence of
benzoyl chloride instead of acetic acid since the formation
of the corresponding dienol benzoate 7c in high yield instead
of product 5c occurred in this case. As far as we know there
are no precedentsforhalogenated derivativesof types 5and 7.
It should be noted that the formation of products 5 can be ex-
plained by C-a protonation of intermediates 4 whereas con-
jugated products 6 would be originated in the case of C-g
protonation. However, all experiments led to the formation
of non-conjugated ketones 5 with total exclusion of their
conjugated isomers 6. In view of these peculiar results, we
focused interest on a comparative study concerning the rel-
ative stabilities of chlorinated and non-chlorinated series
of analogous compounds (Fig. 2) by applying computational
methods. With this purpose, these procedures were tested
firstly by computing fully optimized geometries obtained
by using HF and B3LYP density functional theory methods16
and compared with X-ray structural data of 5f. Table 1 shows
selected bond lengths and bond angles of crystal and calcu-
lated structures at the B3LYP/6-311++G(d,p) and HF/6-
311++G(d,p) levels of theory. An excellent agreement can
be appreciated since differences between bond lengths are
Figure 1. Molecular structure of 5f, showing the crystallographic number-
ing system used.
the total selectivity of these electrochemical processes with
the generation of conjugated isomers 6 being fully avoided.
Geometrical characteristics of compounds of type 5 were
determined by X-ray crystallography of 5f. The molecular
structure found is illustrated in Figure 1. A noteworthy fea-
ture of this structure is its near planarity.
Concerning the electrogeneration of products 5 from com-
pounds 3 (Scheme 1) it seems reasonable to postulate a
two-electron transfer process leading to dienolates 4, which
undergo specific a-protonation to give the final products. An
˚
lower than 0.03 A, whereas between bond angle differences
are less than 0.6ꢀ, which could be attributed to molecular dis-
tortion in the crystal structure forced by packing. As men-
tioned above, a peculiar feature of this structure is its near
planarity. Interplanar angles are listed in Table 2, where an-
gles between the reference plane C(1)–C(3)–C(5) and planes
in this table are lower than 3.1ꢀ. Optimized structures at the
B3LYP/6-31G(d), HF/6-31G(d) and HF/6-311+(d,p) have
also been determined, and the results for ꢀbond lengths and
O
O
O
H
H
H
Ar
Ar
Ar
H
8
H
H
9
O
O
O
O
O
O
Cl
H
Cl
H
Cl
H
˚
bond angles are within ꢁ0.01 A and ꢁ0.3 for the different
Ar
Ar
Ar
Ar
Ar
Ar
models. Next, relative energies (DE0) for isomeric ketone
pairs were computed at the B3LYP/6-311++G(d,p)//
B3LYP/6-31G(d) level of theory. The DE0-values evidence
that non-chlorinated a,b-unsaturated ketones 9 are notori-
ously more stable (DE0z5.4 kcal/mol) than their b,g-unsat-
urated isomers 8 (Fig. 3, series A). The electronic effect
exerted by the ring substituents over the corresponding
energy differences seems to be of little importance.
Cl
Cl
Cl
Cl
6
5
Cl
Cl
11
10
Figure 2. a,b-Unsaturated and b,g-unsaturated isomeric ketone pairs.
Table 1. Selected bond lengths and bond angles of crystal and calculated structures in crystal structure of 5f and their difference
a
b
˚
Crystal structure (A)
˚
Calculated structure (A)
˚
D (A)
˚
Calculated structure (A)
˚
D (A)
Bond
C(9)–C(10)
C(8)–C(9)
C(7)–C(8)
C(4)–C(7)
O(2)–C(7)
Cl(2)–C(10)
Cl(l)–C(10)
1.316(2)
1.497(2)
1.520(2)
1.487(2)
1.221(2)
1.726(2)
1.732(2)
1.327
1.499
1.532
1.489
1.218
1.750
1.745
ꢂ0.011
ꢂ0.002
ꢂ0.012
ꢂ0.002
0.003
1.312
1.503
1.523
1.492
1.192
1.735
1.731
0.004
ꢂ0.006
ꢂ0.003
ꢂ0.005
0.029
ꢂ0.024
ꢂ0.009
ꢂ0.013
0.001
Angle
Crystal structure (ꢀ)
Calculated structure (ꢀ)a
D (ꢀ)
Calculated structure (ꢀ)b
D (ꢀ)
O(2)–C(7)–C(4)
O(2)–C(7)–C(8)
C(4)–C(7)–C(8)
C(9)–C(8)–C(7)
C(10)–C(9)–C(8)
C(9)–C(10)–Cl(2)
C(9)–C(10)–Cl(1)
Cl(2)–C(10)–Cl(1)
120.80(13)
121.16(13)
118.03(12)
112.24(12)
124.29(13)
123.34(12)
122.89(12)
113.76 (8)
121.28
120.70
118.03
112.63
124.88
123.18
122.82
114.00
ꢂ0.48
0.46
0.00
ꢂ0.39
ꢂ0.59
0.16
0.07
ꢂ0.24
121.07
120.94
118.00
112.81
124.41
123.36
122.71
113.92
ꢂ0.27
0.22
0.03
ꢂ0.57
ꢂ0.12
ꢂ0.02
0.18
ꢂ0.16
a
ꢀ
Geometry optimized at the B3LYP/o-311++G(d,p) level of theory.
Geometry optimized at the HF/6-311++G(d,p) level of theory.
b

1178
A. Guirado et al. / Tetrahedron 63 (2007) 1175–1182
Table 2. Interplanar angles of crystal and calculated structures in crystal
structure of 5f and their difference
isomerization of 5e to 6e by refluxing in ethanol–pyridine
solution for a sufficient time to provide fully equilibrated
mixtures of both isomers. The result of this experiment
was the formation of a mixture of compounds 5e and 6e (ra-
tioz1:1), as expected from the calculated Gibbs free ener-
gies of the two isomeric ketones (DG0¼ꢂ0.13 kcal/mol at
the B3LYP/6-31G(d) level of theory). This conclusion also
finds support in different studies on the base-catalyzed de-
conjugation of a,b-unsaturated ketones where results point
towards kinetically controlled protonation of the involved
dienolate anion intermediates.15
Plane
Crystal
structure (ꢀ)
Calculated
D (ꢀ)
structure (ꢀ)a
C(11)–C(2)–C(6)
O(1)–C(2)–C(6)
C(7)–C(2)–C(6)
O(2)–C(2)–C(6)
C(8)–C(2)–C(6)
C(9)–C(2)–C(6)
C(10)–C(2)–C(6)
Cl(1)–C(2)–C(6)
Cl(2)–C(2)–C(6)
0.7
1.0
0.5
2.0
2.1
2.7
3.1
3.3
3.3
0.2
0.1
0.1
0.2
0.1
0.1
0.2
0.3
0.2
0.5
0.9
0.4
1.8
2.0
2.6
2.9
3.0
3.1
In conclusion, an effective method for the synthesis of
a previously unattainable family of compounds, which can
be used for preparing a variety of dichloromethylated hetero-
cyclic compounds, is reported. Versatility, good yields,
easy availability of starting materials, mildness and simple
experimental procedure are noteworthy advantages of this
synthetic methodology.
The angles are between the selected planes and the plane of reference C(1)–
C(3)–C(5).
Angles calculated from geometry optimized at the B3LYP/5-311++G(d,p)
a
level of theory.
By contrast, dichlorinated ketones 6 and 5 exhibit small
differences in energy (DE0z0.5 kcal/mol) (series C). The
electronic influence due to the ring substituents is also
unimportant. This energy equalization is understandable
considering that the +M-effect of the chlorine atoms in iso-
mers 5 compensates the ꢂM-effect of the carbonyl group in
compounds 6. The intermediate location of monochlorinated
ketone pairs 11 and 10 (DE0z2.4 kcal/mol) (Fig. 3, series
B) is fully consistent with this explanation.
3. Experimental
3.1. General
NMR spectra were determined on Bruker AV-200, Bruker
AV-300 or Bruker AV-400 with tetramethylsilane as internal
reference. Electron-impact mass spectra were obtained on
Thermoquest trace MS spectrometer under an ionizing volt-
age of 70 eV. FAB+ data were obtained on Autospec 5000
VG spectrometer. IR spectra (Nujol emulsions) were re-
corded on a Nicolet Impact 400 Spectrometer. Microanaly-
ses were performed on a Carlo Erba EA-1108 analyzer.
It should be noted that the natural14 charge-values at the b-
carbon atoms for ketones 9a (series A), 11a (series B) and
6a (series C), computed at B3LYP/6-31G(d) level of theory
are ꢂ0.108, ꢂ0.154 and ꢂ0.189 (values in electrons), re-
spectively. This means that the contribution of dipolar ca-
nonical structures to resonance hybrids placing a positive
charge density on C-b (Fig. 2) is being inhibited by interac-
tion with the vicinal electron-withdrawing groups (CH2Cl
and CHCl2).
€
Melting points were determined on a Buchi Melting point
B-540, and are uncorrected. Electrochemical experiments
were performed with an Amel 552 potentiostat coupled to
an Amel 721 integrator.
All computations were performed with the Spartan’04 pack-
age program.16 The most stable conformers were determined
by using the MMFF molecular mechanics method.17 Next,
these conformers were used as input for ab initio molecular
orbital and density functional theory calculations of geome-
try optimizations at the Hartree–Fock and B3LYP18 levels of
theory with the 6-31G(d) basis set. Selected geometry opti-
mizations were also carried out at these levels of theory with
the 6-311+G(d,p) and 6-311++G(d,p) bases. There were no
significant differences between the results obtained with
the different basis sets. Frequency calculations were per-
formed at the same level of theory as the geometry optimiza-
tions to characterize the stationary points as local minima
(equilibrium structures) and to evaluate the zero-point en-
ergy (ZPE). No scaling procedures were used. Single-point
energies were calculated with the 6-311++G(d,p) basis.
Taking into account the above results, it seems reasonable
to conclude that the observed total priority towards the for-
mation of products 5 in detriment to formation of products
6 should not be due to thermodynamic control but should
be driven by a remarkably efficient kinetic control. An evi-
dence of this was found by attempting a base-catalyzed
3.2. Preparation of 1-aryl-4,4,4-trichlorobut-2-en-1-
ones (3)
Compounds 3a–d, method A: The appropriate ketone 2
(35 mmol) in sulfuric acid (100 mL) was stirred at room
temperature for 2 h. The reaction product was isolated by
dropping the reaction mixture into ice water (400 mL) and
filtering the yellow solid precipitated, which was air-dried
and crystallized in the appropriate solvent.
Figure 3. Values of DE0¼E0(b,g-unsaturated ketone)ꢂE0(a,b-unsaturated
isomer) for the non-chlorinated (series A), monochlorinated (series B)
and dichlorinated isomeric ketone pairs (series C) computed at the
B3LYP/6-311++G(d,p)//B3LYP/6-31G(d) level of theory and including
ZPE corrections calculated at the same level as geometry optimization.

A. Guirado et al. / Tetrahedron 63 (2007) 1175–1182
1179
Compounds 3e–j, method B: The appropriate ketone 2
(33 mmol), p-toluenesulfonic acid monohydrate (17 mmol)
and toluene (300 mL) were refluxed with a Dean–Stark
water separator until a total conversion of the starting material
2 was observed by TLC (silica gel/ethyl acetate–petroleum
ether, ratio 1:9). Then the solvent was removed under re-
duced pressure, the residue was dissolved in chloroform
and washed with aqueous sodium bicarbonate and water.
The organic layer was dried over anhydrous magnesium sul-
fate and chloroform was removed in vacuo leaving a solid
residue that was crystallized in the appropriate solvent.
149 (45), 75 (36); IR (Nujol): 1662, 1621, 1578, 1398,
1322, 1278, 1101, 1069, 1006, 962, 766 cmꢂ1. Anal. Calcd
forC10H6BrCl3O:C, 36.57;H, 1.84.Found: C, 36.46;H, 1.72.
3.2.5. 4,4,4-Trichloro-1-(4-tolyl)but-2-en-1-one (3e).
Yield 89%. White plates, mp 89–90 ꢀC (ethanol). 1H NMR
d
(CDCl3, 300 MHz): 2.44 (s, 3H), 7.25 (d, 1H,
J¼14.7 Hz), 7.31 (d, 2H, J¼8.1 Hz), 7.41 (d, 1H,
J¼14.7 Hz), 7.89 (d, 2H, J¼8.1 Hz); 13C NMR d (CDCl3,
75.4 MHz): 21.85 (CH3), 93.13 (CCl3), 124.24 (CH),
128.97 (CH), 129.69 (CH), 134.39 (C), 145.07 (C), 145.21
(CH), 188.36 (CO); MS, m/z (%): 266 (M++4, 28), 264
(M++2, 75), 262 (M+, 76), 227 (24), 102 (69), 163 (70),
145 (45), 128 (39), 119 (100), 91 (74), 73 (44); IR (Nujol):
1668, 1604, 1408, 1330, 1284, 1183, 1124, 1097, 959,
1014, 959, 872, 758 cmꢂ1. Anal. Calcd for C11H9Cl3O: C,
50.13; H, 3.44. Found: C, 50.26; H, 3.41.
3.2.1. 4,4,4-Trichloro-1-phenylbut-2-en-1-one (3a). Yield
94%. White plates, mp 101–102 ꢀC (ethanol), (lit.:13b
1
mp 100 ꢀC). H NMR d (CDCl3, 400 MHz): 7.26 (d, 1H,
J¼14.5 Hz), 7.40 (d, 1H, J¼14.5 Hz), 7.51 (t, 2H,
J¼7.4 Hz), 7.62 (tt, 1H, J¼7.4 Hz, J¼1.2 Hz), 7.97 (dd, 2H,
J¼7.4 Hz, J¼1.2 Hz); 13C NMR d (CDCl3, 100.8 MHz):
93.04 (CCl3), 124.25 (CH), 128.80 (CH), 128.97 (CH),
133.91 (CH), 136.90 (C), 145.51 (CH), 188.84 (CO); MS,
m/z (%): 252 (M++4, 1), 250 (M++2, 2), 248 (M+, 2), 149
(14), 105 (100), 77 (37); IR (Nujol): 1674, 1626, 1594,
1341, 1277, 1011, 953, 876, 767, 739 cmꢂ1. Anal. Calcd
for C10H7Cl3O: C, 48.14; H, 2.83. Found: C, 48.60; H, 2.91.
3.2.6. 4,4,4-Trichloro-1-(4-methoxyphenyl)but-2-en-1-
one (3f). Yield 80%. Pale yellow prisms, mp 66–68 ꢀC (eth-
anol). 1H NMR d (CDCl3, 400 MHz): 3.89 (s, 3H), 6.99 (d,
2H, J¼8.9 Hz), 7.25 (d, 1H, J¼14.5 Hz), 7.41 (d, 1H,
J¼14.5 Hz), 7.99 (d, 2H, J¼8.9 Hz); 13C NMR d (CDCl3,
100.8 MHz): 55.65 (CH3), 93.23 (CCl3), 114.23 (CH),
124.20 (CH), 129.92 (C), 131.27 (CH), 144.87 (CH),
164.33 (C), 187.02 (CO); MS, m/z (%): 282 (M++4, 54),
280 (M++2, 54), 278 (M+, 54), 243 (24), 245 (18), 217
(74), 215 (62), 208 (25), 179 (74), 145 (60), 135 (100), 92
(74), 77 (64); IR (Nujol): 1670, 1597, 1570, 1425, 1327,
1264, 1176, 1099, 1015, 872, 840, 762, 719 cmꢂ1. Anal.
Calcd for C11H9Cl3O2: C, 47.26; H, 3.25. Found: C, 47.36;
H, 3.34.
3.2.2. 4,4,4-Trichloro-1-(4-fluorophenyl)but-2-en-1-one
(3b). Yield 95%. White plates, mp 117–119 ꢀC (hexane),
1
(lit.:13c mp 117–118 ꢀC). H NMR d (CDCl3, 200 MHz):
7.20 (t, 2H, J¼8.8 Hz), 7.27 (d, 1H, J¼14.6 Hz), 7.39 (d,
1H, J¼14.6 Hz), 8.04 (dd, 2H, J¼8.8 Hz, J¼5.4 Hz); 13C
NMR d (CDCl3, 50.4 MHz): 92.87 (CCl3), 116.22 (d,
J¼22.1 Hz) (CH), 123.71 (CH), 131.54 (d, J¼9.5 Hz)
(CH), 133.24 (d, J¼2.8 Hz) (C), 145.67 (CH), 166.25 (d,
J¼256.9 Hz) (C), 187.18 (CO); MS, m/z (%): 270 (M++4,
4), 268 (M++2, 10), 266 (M+, 11), 231 (16), 196 (12), 203
(37), 205 (27), 123 (100), 95 (53), 75 (34); IR (Nujol):
1672, 1621, 1591, 1333, 1420, 1212, 1162, 962, 880, 814,
758 cmꢂ1. Anal. Calcd for C10H6Cl3FO: C, 44.90; H, 2.26.
Found: C, 44.70; H, 2.11.
3.2.7. 4,4,4-Trichloro-1-(4-nitrophenyl)but-2-en-1-one
(3g). Yield 82%. Yellow prisms, mp 109 ꢀC (ethanol),
1
(lit.:13e mp 102–103 ꢀC). H NMR d (CDCl3, 200 MHz):
7.33 (d, 1H, J¼14.4 Hz), 7.40 (d, 1H, J¼14.4 Hz), 8.16 (d,
2H, J¼8.8 Hz), 8.38 (d, 2H, J¼8.8 Hz); 13C NMR
d (CDCl3, 50.4 MHz): 92.45 (CCl3), 123.23 (CH), 124.19
(CH), 129.80 (CH), 141.25 (C), 146.94 (CH), 150.73 (C),
187.59 (CO); MS, m/z (%): 260 (48), 258 (65), 230 (28),
184 (36), 150 (100), 104 (47), 92 (29), 76 (50); IR (Nujol):
1707, 1686, 1625, 1599, 1514, 1209, 1092, 1011, 963,
855, 780, 770 cmꢂ1. Anal. Calcd for C10H6Cl3NO3: C,
40.78; H, 2.05; N, 4.76. Found: C, 40.62; H, 1.98; N 4.67.
3.2.3. 4,4,4-Trichloro-1-(4-chlorophenyl)but-2-en-1-one
(3c). Yield 90%. Pale yellow prisms, mp 116–117 ꢀC (etha-
nol) (lit.:13c mp 115–116 ꢀC). 1H NMR d (CDCl3,
200 MHz): 7.26 (d, 1H, J¼14.6 Hz), 7.35 (d, 1H,
J¼14.6 Hz), 7.50 (d, 2H, J¼8.8 Hz), 7.93 (d, 2H,
J¼8.8 Hz); 13C NMR d (CDCl3, 50.4 MHz): 92.83 (CCl3),
123.59 (CH), 129.34 (CH), 130.19 (CH), 135.12 (C),
140.57 (C), 145.89 (CH), 187.59 (CO); MS, m/z (%): 286
(M++4, 17), 284 (M++2, 31), 282 (M+, 23), 247 (25), 249
(26), 219 (65), 221 (67), 185 (77), 139 (100), 141 (65),
111 (78), 73 (64); IR (Nujol): 1674, 1623, 1589, 1279,
1211, 1182, 1091, 1015, 961, 873, 776 cmꢂ1. Anal. Calcd
for C10H6Cl4O: C, 42.30; H, 2.13. Found: C, 42.49; H, 2.22.
3.2.8. 4,4,4-Trichloro-1-(2,4-dimethylphenyl)but-2-en-1-
one (3h). Yield 85%. Yellow plates, mp 72–73 ꢀC (cyclo-
hexane). H NMR d (CDCl3, 400 MHz): 2.38 (s, 3H), 2.49
1
(s, 3H), 7.14 (d, 1H, J¼14.7 Hz), 7.06 (d, 1H, J¼14.7 Hz),
7.11 (br s, 2H), 7.52 (d, 1H, J¼8.2 Hz); 13C NMR
d (CDCl3, 50.4 MHz): 21.55 (CH3), 21.10 (CH3), 93.03
(CCl3), 126.52 (CH), 127.70 (CH), 129.67 (CH), 132.95
(CH), 134.31 (C), 139.10 (C), 142.88 (C), 145.18 (CH),
192.39 (CO); MS, m/z (%): 177 (6), 159 (11), 146 (9), 133
(100), 105 (19), 77 (7); FAB+: 277 (M+H+); IR (Nujol):
1699, 1609, 1312, 1281, 1138, 1008, 973, 770, 760,
718 cmꢂ1. Anal. Calcd for C12H11Cl3O: C, 51.92; H, 3.99.
Found: C, 52.03; H, 4.07.
3.2.4. 1-(4-Bromophenyl)-4,4,4-trichlorobut-2-en-1-one
(3d). Yield 84%. Pale yellow needles, mp 122 ꢀC (ethanol)
1
(lit.:13c mp 119–120 ꢀC). H NMR d (CDCl3, 400 MHz):
7.27 (d, 1H, J¼14.5 Hz), 7.36 (d, 1H, J¼14.5 Hz), 7.67 (d,
2H, J¼8.6 Hz), 7.85 (d, 2H, J¼8.6 Hz); 13C NMR
d (CDCl3, 100.8 MHz): 92.81 (CCl3), 123.52 (CH), 129.35
(C), 130.24 (CH), 132.33 (CH), 135.51 (C), 145.93 (CH),
187.82 (CO); MS, m/z (%): 330 (M++4, 19), 328 (M++2,
30), 326 (M+, 15), 265 (33), 229 (14), 183 (100), 185 (98),
3.2.9. 1-(4-Biphenylyl)-4,4,4-trichlorobut-2-en-1-one
(3i). Yield 75%. Pale yellow plates, mp 120–121 ꢀC (etha-
nol). 1H NMR d (CDCl3, 400 MHz): 7.30 (d, 1H,

1180
A. Guirado et al. / Tetrahedron 63 (2007) 1175–1182
J¼14.5 Hz), 7.40–7.50 (m, 4H), 7.63 (d, 2H, J¼7.5 Hz),
7.73 (d, 2H, J¼8.3 Hz), 8.06 (d, 2H, J¼8.3 Hz); 13C NMR
d (CDCl3, 100.8 MHz): 93.08 (CCl3), 124.16 (CH), 127.37
(CH), 127.58 (CH), 128.93 (CH), 129.10 (CH), 129.45
(CH), 135.54 (C), 139.62 (C), 145.45 (CH), 146.68 (C),
188.31 (CO); MS, m/z (%): 328 (M++4, 18), 326 (M++2,
49), 324 (M+, 50), 261 (22), 225 (50), 191 (32), 181 (100),
152 (73), 127 (20); IR (Nujol): 1673, 1621, 1603, 1404,
1096, 1005, 960, 779, 772, 750, 696 cmꢂ1. Anal. Calcd for
C16H11Cl3O: C, 59.02; H, 3.41. Found: C, 58.97; H, 3.37.
3.3.1. 4,4-Dichloro-1-phenylbut-3-en-1-one (5a). Yield
95%. Pale yellow prisms, mp 50–51 ꢀC (petroleum ether).
1H NMR d (CDCl3, 200 MHz): 3.99 (d, 2H, J¼6.8 Hz),
6.34 (t, 1H, J¼6.8 Hz), 7.44–7.53 (m, 2H), 7.56–7.65 (m,
1H), 7.94–8.00 (m, 2H); 13C NMR d (CDCl3, 50.4 MHz):
39.26 (CH2), 122.61 (CH), 122.74 (CCl2), 128.23 (CH),
128.85 (CH), 133.71 (CH), 136.07 (C), 195.02 (CO); MS,
m/z (%): 105 (100), 77 (47); FAB+: 215 (M+H+); IR (Nujol):
1684, 1625, 1594, 1580, 1347, 1248, 1073, 992, 904, 814,
690, 608 cmꢂ1. Anal. Calcd for C10H8Cl2O: C, 55.84;
H, 3.75. Found: C, 55.62; H, 3.81.
3.2.10. 4,4,4-Trichloro-1-(naphthalen-2-yl)but-2-en-1-
one (3j). Yield 87%. Pale yellow plates, mp 98–99 ꢀC
(ethanol). 1H NMR d (CDCl3, 200 MHz): 7.33 (d, 1H,
J¼14.6 Hz), 7.56 (d, 1H, J¼14.6 Hz), 7.53–7.67 (m, 2H),
7.86–8.06 (m, 4H), 8.46 (br s, 1H); 13C NMR d (CDCl3,
50.4 MHz): 93.10 (CCl3), 124.07 (CH), 127.16 (CH),
127.95 (CH), 129.02 (CH), 129.13 (CH), 129.77 (CH),
130.85 (CH), 132.43 (C), 134.19 (C), 135.92 (C), 145.44
(CH), 188.55 (CO); MS, m/z (%): 302 (M++4, 17), 300
(M++2, 50), 298 (M+, 52), 235 (19), 199 (19), 181 (33),
165 (47), 155 (100), 127 (93), 77 (22); IR (Nujol): 1673,
1623, 1593, 1314, 1190, 1126, 1097, 954, 862, 776, 761,
742, 681 cmꢂ1. Anal. Calcd for C14H9Cl3O: C, 56.13;
H, 3.03. Found: C, 55.92; H, 2.97.
3.3.2. 4,4-Dichloro-1-(4-fluorophenyl)but-3-en-1-one
(5b). Yield 96%. Chromatography (silica gel/ethyl ace-
tate–hexane, ratio 1:1) gave yellow powder, mp 32–34 ꢀC.
1H NMR d (CDCl3, 400 MHz): 3.88 (d, 2H, J¼6.6 Hz),
6.33 (t, 1H, J¼6.6 Hz), 7.16 (t, 2H, J¼8.6 Hz), 8.00 (dd, 2H,
J¼8.6 Hz, J¼5.3 Hz); 13C NMR d (CDCl3, 100.8 MHz):
39.15 (CH2), 116.01 (d, J¼22.1 Hz) (CH), 122.37 (CH),
122.88 (CCl2), 130.91 (d, J¼9.3 Hz) (CH), 132.46 (d,
J¼2.9 Hz) (C), 166.01 (d, J¼255.7 Hz) (C), 193.41 (CO);
IR (Nujol): 3055, 1684, 1625, 1600, 1057, 1242, 1203,
1160, 992, 905, 841, 802, 639 cmꢂ1. Anal. Calcd for
C10H7Cl2FO: C, 51.53; H, 3.03. Found: C, 51.40; H, 3.12.
3.3.3. 4,4-Dichloro-1-(4-chlorophenyl)but-3-en-1-one
(5c). Yield 97%. Chromatography (silica gel/ethyl acetate–
hexane, ratio 1:9) gave white powder, mp 58–59 ꢀC. 1H
NMR d (CDCl3, 200 MHz): 3.87 (d, 2H, J¼6.6 Hz), 6.32 (t,
1H, J¼6.6 Hz), 7.47 (d, 2H, J¼8.6 Hz), 7.92 (d, 2H,
J¼8.6 Hz); 13C NMR d (CDCl3, 50.4 MHz): 39.22 (CH2),
122.23 (CH), 123.04 (CCl2), 129.19 (CH), 129.63 (CH),
134.37 (C), 140.23 (C), 193.79 (CO); IR (Nujol): 1673, 1630,
1590, 1341, 1210, 1093, 996, 894, 812, 788 cmꢂ1. Anal. Calcd
for C10H7Cl3O: C, 48.14; H, 2.83. Found: C, 47.82; H, 2.84.
3.3. Electrogeneration of 1-aryl-4,4-dichlorobut-3-en-1-
ones (5)
Reductive electrolyses of compounds 3 were carried out un-
der a constant cathodic potential in a concentric cylindrical
cell with two compartments separated by a circular glass
frit (medium) diaphragm. A mercury pool (diameter 5 cm;
tip of the Luggin-capillary situated on the edge of the
pool) was used as the cathode and a platinum plate as the
anode. The catholyte was magnetically stirred. The temper-
ature was kept at approximately 18 ꢀC by external cooling.
The reductions were performed in MeCN (60 mL)–AcOH
(10 mL)–LiClO4 0.47 M; 55 mL and 15 mL were placed
in the cathodic and the anodic compartments, respectively.
Sodium acetate (1 g) was placed in the anode compartment.
Solutions of 3 (5 mmol) were electrolyzed under the follow-
ing cathodic potentials,19 which were selected in order to
provide operative current intensities (close to 220 mA at
the beginning and 10 mA at the end): 3a (ꢂ0.20); 3c,d,i
(ꢂ0.30); 3g (ꢂ0.40); 3b,f (ꢂ0.50); 3j (ꢂ0.60); 3e
(ꢂ0.72); 3h (ꢂ0.80) V versus SCE. The electricity con-
sumption was 2 F/mol. Isolation of products 5 was carried
out by removing the solvent in vacuo, adding water
(150 mL) and collecting the resulting solid by filtration.20
3.3.4. 1-(4-Bromophenyl)-4,4-dichlorobut-3-en-1-one
(5d). Yield 98%. White plates, mp 79–80 ꢀC (petroleum
ether). 1H NMR d (CDCl3, 400 MHz): 3.86 (d, 2H,
J¼6.6 Hz), 6.31 (t, 1H, J¼6.6 Hz), 7.63 (d, 2H,
J¼8.6 Hz), 7.83 (d, 2H, J¼8.6 Hz); 13C NMR d (CDCl3,
100.8 MHz): 39.20 (CH2), 122.18 (CH), 123.04 (CCl2),
128.98 (C), 129.71 (CH), 132.18 (CH), 134.73 (CH),
193.98 (CO); MS, m/z (%): 183 (100), 185 (98), 157 (28),
155 (27), 76 (20), 76 (17); FAB+: 293 (M+H+); IR (Nujol):
1684, 1628, 1583, 1339, 1241, 1087, 1073, 988, 904, 792,
613 cmꢂ1. Anal. Calcd for C10H7BrCl2O: C, 40.86; H,
2.40. Found: C, 40.59; H, 2.32.
3.3.5. 4,4-Dichloro-1-(4-tolyl)but-3-en-1-one (5e). Yield
98%. White plates, mp 76–77 ꢀC (petroleum ether). 1H
NMR d (CDCl3, 200 MHz): 2.42 (s, 3H), 3.85 (d, 2H,
J¼6.0 Hz), 6.33 (t, 1H, J¼6.0 Hz), 7.27 (d, 2H,
J¼8.0 Hz), 7.86 (d, 2H, J¼8.0 Hz); 13C NMR d (CDCl3,
50.4 MHz): 21.73 (CH3), 39.13 (CH2), 122.47 (CCl2),
122.83 (CH), 128.32 (CH), 129.50 (CH), 133.59 (C),
144.60 (C), 194.59 (CO); FAB+: 229 (M+H+); IR (Nujol):
1679, 1607, 1347, 1243, 1201, 1184, 1088, 996, 991, 905,
793, 770, 638 cmꢂ1. Anal. Calcd for C11H10Cl2O: C,
57.67; H, 4.40. Found: C, 57.38; H, 4.41.
These syntheses were found to be reproducible when follow-
ing a procedure like the above but using graphite (area
12 cm2) instead of mercury as cathodic material, and plati-
num (area 8 cm2) as cathodic material with an operating
potential of ꢂ1.00 V versus SCE, except in the reduction of
3g, in which the electrolysis was carried under a potential
of ꢂ0.55 V versus SCE. The current intensity was about
100 mA at the beginning, and 20 mA at the end. The elec-
tricity consumption was 2 F/mol. Analogous results were
obtained in experiments under these electrolysis conditions
but working in MeCN (60 mL)–AcOH (10 mL)–H2O
(5 mL)–NaBF4 0.45 M.
3.3.6. 4,4-Dichloro-1-(4-methoxyphenyl)but-3-en-1-one
(5f). Yield 96%. White plates, mp 72–73 ꢀC (petroleum

A. Guirado et al. / Tetrahedron 63 (2007) 1175–1182
1181
ether). 1H NMR d (CDCl3, 300 MHz): 3.83 (d, 2H,
J¼6.6 Hz), 3.87 (s, 3H), 6.33 (t, 1H, J¼6.6 Hz), 6.95 (d,
2H, J¼8.7 Hz), 7.94 (d, 2H, J¼8.7 Hz); 13C NMR d
(CDCl3, 75.4 MHz): 38.91 (CH2), 55.54 (CH3), 113.94
(CH), 122.38 (CCl2), 123.00 (CH), 139.06 (C), 130.51
(CH), 163.91 (C), 193.51 (CO); FAB+: 245 (M+H+); IR
(Nujol): 1677, 1601, 1511, 1354, 1261, 1247, 1174, 1030,
993, 904, 833, 802 cmꢂ1. Anal. Calcd for C11H10Cl2O2:
C, 53.90; H, 4.11. Found: C, 53.69; H, 4.02.
129.06 (CH), 134.72 (C), 139.68 (C), 146.36 (C), 194.57
(CO); FAB+: 291 (M+H+); IR (Nujol): 1678, 1628, 1605,
1342, 1249, 1201, 1089, 989, 906, 804, 759, 691 cmꢂ1
.
Anal. Calcd for C16H12Cl2O: C, 66.00; H, 4.15. Found: C,
65.88; H, 4.10.
3.3.10. 4,4-Dichloro-1-(naphthalen-2-yl)but-3-en-1-one
(5j). Yield 96%. Pale yellow needles, mp 80–81 ꢀC (petro-
leum ether). H NMR d (CDCl3, 400 MHz): 4.02 (d, 2H,
1
J¼6.6 Hz), 6.39 (t, 1H, J¼6.6 Hz), 7.54–7.63 (m, 2H),
7.87 (s ancho, 1H), 7.90 (d, 1H, J¼8.7 Hz), 7.97 (d, 1H,
J¼8.0 Hz), 8.01 (dd, 1H, J¼8.7 Hz, J¼1.8 Hz), 8.47 (br s,
1H); 13C NMR d (CDCl3, 100.8 MHz): 39.34 (CH2),
112.74 (CH), 123.73 (CH), 127.73 (CH), 127.89 (CH),
128.89 (CH), 129.68 (CH), 130.06 (CH), 132.49 (C),
133.37 (C), 135.83 (C), 194.95 (CO); FAB+: 265 (M+H+);
IR (Nujol): 1679, 1624, 1360, 1336, 1172, 1126, 964, 944,
911, 804, 769, 745 cmꢂ1. Anal. Calcd for C14H10Cl2O: C,
63.42; H, 3.80. Found: C, 62.92; H, 3.75.
Crystal
a¼14.0637(9) A, b¼13.7598(9) A, c¼5.6360(4) A, a¼90 ,
dcalcd¼1.507 Mg/m3, m¼0.575 mmꢂ1, T¼100(2) K. Colour-
less block-like crystals were grown by evaporation of a solu-
tion of 5f; 6232 reflections were measured (2qmax 52.7ꢀ)
using monochromated Mo Ka radiation on a Bruker Smart
Apex CCD machine, of which 2196 were unique and used
for all calculations (program ShelXL-97, G. M. Sheldrick,
data:
˚
C11H10Cl2O2,
˚
M¼245.09,
˚
P21/c,
ꢀ
3
b¼97.9751(11)ꢀ, g¼90ꢀ, V¼1080.10(13) A , Z¼4,
˚
€
University of Gottingen). The structure was solved by direct
methods, and was refined anisotropically on F2. Hydrogen
atoms were included using a riding model or rigid methyl
group. The final wR(F2) was 0.0812 with conventional
R(F) 0.0324, for 137 parameters and 3 restraints; highest
peak 0.00239, hole ꢂ0.00325 e/pm.
3.4. Isomerization of 5e to 6e
A mixture of 4,4-dichloro-1-(4-tolyl)but-3-en-1-one 5e
(1.8 mmol), pyridine (3.9 mmol) and ethanol (15 mL) was
refluxed for 5 h. Evaporation to dryness under reduced pres-
sure yielded a crude material that was stirred in cold water
(25 mL) and extracted with ether (2ꢃ25 mL). The combined
extracts were washed with hydrochloric acid (5%; 25 mL),
water (2ꢃ20 mL) and dried with anhydrous magnesium sul-
fate. The solvent was evaporated under reduced pressure
leaving a mixture exclusively formed by the starting material
and 4,4-dichloro-1-(4-tolyl)-2-buten-1-one 6e (ratio 1:1),
which was isolated by column chromatography (silica gel/
tert-butyl methyl ether–hexane, ratio 1:19).
Tables of fractional atomic coordinates, thermal parameters,
bond lengths and angles have been deposited at the Cam-
bridge Crystallographic Center (CCDC 607589).
3.3.7. 4,4-Dichloro-1-(4-nitrophenyl)but-3-en-1-one (5g).
Yield 72%. Yellow needles, mp 103–105 ꢀC (cyclohexane).
1H NMR d (CDCl3, 400 MHz): 3.96 (d, 2H, J¼6.6 Hz), 6.32
(t, 1H, J¼6.6 Hz), 8.14 (d, 2H, J¼8.9 Hz), 8.35 (d, 2H,
J¼8.9 Hz); 13C NMR d (CDCl3, 100.8 MHz): 39.73
(CH2), 121.44 (CH), 123.76 (CCl2), 124.11 (CH), 129.30
(CH), 140.41 (C), 150.69 (C), 193.52 (CO); FAB+: 260
(M+H+); IR (Nujol): 1697, 1606, 1520, 1245, 1199, 996,
904 cmꢂ1. Anal. Calcd for C10H7Cl2NO3: C, 46.18; H,
2.71; N, 5.39. Found: C, 45.85; H, 2.66; N, 5.57.
3.4.1. 4,4-Dichloro-1-(4-tolyl)but-2-en-1-one (6e). Yield
1
45%. White needles, mp 34–35 ꢀC (petroleum ether). H
NMR d (CDCl3, 400 MHz): 2.44 (s, 3H), 6.37 (d, 1H,
J¼6.5 Hz), 7.06 (dd, 1H, J¼15.0 Hz, J¼6.5 Hz), 7.19 (d,
1H, J¼15.0 Hz), 7.30 (d, 1H, J¼8.2 Hz), 7.87 (d, 1H,
J¼8.2 Hz); 13C NMR d (CDCl3, 100.8 MHz): 21.75
(CH3), 68.82 (CHCl2), 126.06 (CH), 128.85 (CH), 129.54
(CH), 134.33 (C), 141.56 (CH), 144.71 (C), 188.72 (CO);
MS, m/z (%): 230 (M++2, 4), 228 (M+, 6), 158 (10), 145
(5), 119 (100), 91 (40), 69 (17), 65 (14); IR (Nujol): 1666,
1627, 1602, 1342, 1306, 1251, 1239, 1182, 1108, 1012,
967, 745, 700 cmꢂ1. Anal. Calcd for C11H10Cl2O: C,
57.67; H, 4.40. Found: C, 57.31; H, 4.37.
3.3.8. 4,4-Dichloro-1-(2,4-dimethylphenyl)but-3-en-1-
one (5h). Yield 97%. Chromatography (silica gel/ethyl ace-
tate–hexane, ratio 1:2) gave yellow oil. 1H NMR d (CDCl3,
400 MHz): 2.35 (s, 3H), 2.50 (s, 3H), 3.80 (d, 2H,
J¼6.8 Hz), 6.29 (t, 1H, J¼6.8 Hz), 7.07 (s, 1H), 7.09 (s,
1H), 7.61 (d, 1H, J¼8.4 Hz); 13C NMR d (CDCl3,
100.8 MHz): 21.43 (CH3), 21.78 (CH3), 41.47 (CH2),
122.38 (CCl2), 123.13 (CH), 126.52 (CH), 129.29 (CH),
133.21 (CH), 133.21 (CH), 133.46 (C), 139.48 (C), 142.80
(C), 197.58 (CO); IR (film): 3351, 3239, 3057, 3020,
2965, 2923, 1685, 1612, 1566, 1452, 1334, 1205, 985,
882, 803, 725, 633 cmꢂ1. Anal. Calcd for C12H12Cl2O: C,
59.28; H, 4.97. Found: C, 59.23; H, 5.17.
3.5. Preparation of 1-(4-bromophenyl)-4,4-dichloro-1,3-
butadien-1-yl benzoate (7d)
1-(4-Bromophenyl)-4,4,4-trichlorobut-2-en-1-one 3d (5 mmol)
was electrolyzed operating as described to generate com-
pounds 5 but with the experiment being carried out in the
presence of benzoyl chloride (30 mmol) instead of acetic
acid. The cathodic potential was ꢂ0.30 V versus SCE and
the electricity consumption was 2 F/mol. The catholyte solu-
tion was dropped onto concentrated ammonium hydroxide
(50 mL)–ice (200 g) and the mixture was extracted with
ether. The ether layers were collected and dried over anhy-
drous magnesium sulfate, concentrated to 20 mL and cooled
to ꢂ20 ꢀC for 2 h. The solid precipitate (benzamide) was
3.3.9. 1-(4-Biphenylyl)-4,4-dichlorobut-3-en-1-one (5i).
Yield 95%. Pale yellow needles, mp 113–114 ꢀC (petroleum
ether). 1H NMR d (CDCl3, 200 MHz): 3.91 (d, 2H,
J¼6.6 Hz), 6.36 (t, 1H, J¼6.6 Hz), 7.52–7.40 (m, 3H),
7.62 (dd, 2H, J¼8.4 Hz, J¼1.5 Hz), 7.69 (d, 2H,
J¼8.4 Hz), 8.03 (d, 2H, J¼8.4 Hz); 13C NMR d (CDCl3,
50.4 MHz): 39.31 (CH2), 122.67 (CCl2), 127.33 (CH),
127.49 (CH), 128.46 (CH), 128.83 (CH), 128.83 (CH),

1182
A. Guirado et al. / Tetrahedron 63 (2007) 1175–1182
5. (a) Trahanovsky, W. S.; Macaulay, D. B. J. Org. Chem. 1973,
38, 1497; (b) Schrekker, H. S.; Micskei, K.; Hajdu, C.;
Patonay, T.; Bolster, M. W. G.; Wessjohann, L. A. Adv. Synth.
Catal. 2004, 346, 731; (c) Sakurai, H.; Tanabe, K.; Narasaka,
K. Chem. Lett. 1999, 309; (d) Smit, W. A.; Semenovsky,
A. V.; Kucherov, V. F.; Chernova, T. N.; Krimer, M. Z.;
Lubinskaya, O. V. Tetrahedron Lett. 1971, 12, 3101.
removed by filtration. The filtrate was concentrated to dry-
ness under reduced pressure and the residual material was
crystallized from cool methanol.
Yield 72%. Pale yellow needles, mp 113–114 ꢀC (petroleum
ether). 1H NMR d (CDCl3, 400 MHz): 6.62 (d, 1H,
J¼10.8 Hz), 6.68 (d, 1H, J¼10.8 Hz), 7.39 (d, 2H,
J¼7.1 Hz), 7.47 (d, 2H, J¼7.1 Hz), 7.55 (t, 2H, J¼7.6 Hz),
7.69 (t, 1H, J¼7.6 Hz), 8.21 (d, 2H, J¼7.6 Hz); 13C NMR
d (CDCl3, 100.8 MHz): 112.06 (CH), 122.58 (CH), 123.67
(C), 124.26 (C), 126.44 (CH), 128.34 (C), 128.98 (CH),
130.42 (CH), 132.09 (CH), 132.95 (C), 134.34 (CH),
147.76 (C), 164.14 (CO); MS, m/z (%): 183 (2), 149 (8),
105 (100), 77 (73); FAB+: 397 (M+H+); IR (Nujol): 1734,
1585, 1253, 1240, 1172, 1082, 1064, 1005, 914, 831, 810,
713, 689 cmꢂ1. Anal. Calcd for C17H11BrCl2O2: C, 51.26;
H, 2.84. Found: C, 51.29; H, 2.79.
6. Lutniskii, F. I. Chem. Rev. 1975, 75, 259.
7. For previous papers showing the interest of this line of work
ꢀ
see: (a) Guirado, A.; Andreu, R.; Galvez, J.; Jones, P. G.
Tetrahedron 2002, 58, 9853; (b) Guirado, A.; Andreu, R.;
ꢀ
Martiz, B.; Galvez, J. Tetrahedron 2004, 60, 987; (c)
Guirado, A.; Andreu, R.; Martiz, B.; Bautista, D.; Ramırez de
ꢀ
Arellano, C.; Jones, P. G. Tetrahedron 2006, 62, 6172 and
references cited therein.
8. Guirado, A.; Martiz, B.; Andreu, R. Tetrahedron Lett. 2004, 45,
8523.
9. Unpublished results.
10. Hill, R. A. Comprehensive Organic Functional Groups
Transformations; Kirby, G. W., Katritzky, A. R., Meth-Cohn,
O., Rees, Ch. W., Eds.; Elsevier: Oxford, 1995; Vol. 4, p 11.
11. (a) Fujisawa, T.; Ito, T.; Fujimoto, K.; Shimizu, M.
Tetrahedron Lett. 1997, 38, 1593; (b) Fujisawa, T.; Shimizu,
M. Jpn. Pat. JP 09,227,441, 1997; Chem. Abstr. 1997,
127, 262526; (c) Fujisawa, Y.; Shimizu, M. Jpn. Pat. JP
1,087,547, 1998; Chem. Abstr. 1998, 128, 321379.
12. (a) Funabiki, K.; Honma, N.; Hashimoto, W.; Matsui, M. Org.
Lett. 2003, 5, 2059; (b) Miura, K.; Nakagawa, T.; Hosomi, A.
J. Am. Chem. Soc. 2002, 124, 536.
Acknowledgements
We gratefully acknowledge the financial support of the Min-
ꢀ
isterio de Educacion y Ciencia (project CTQ2004-06427)
and the Fundacion Seneca of the Comunidad Autonoma de
ꢀ
ꢀ
ꢀ
ꢀ
la Region de Murcia (project 03035/PI/05). The author
B.M. thanks the Fundacion CajaMurcia for a grant.
ꢀ
Supplementary data
13. (a) Caujolle, F.; Couturier, P.; Dulaurans, C. Bull. Soc. Chim.
Fr. 1950, 17, 19; (b) Wislicenus, J. Chem. Ber. 1893, 26, 908;
(c) Druey, J. U.S. Patent 2,659,757, 1953; (d) McDonald,
B. G. Eur. Pat. 22,321, 1980; (e) Bobylev, M. M.; Putsykin,
Y. G.; Velesevich, S. M.; Andreeva, E. I.; Sanin, M. A.; Zaikin,
B. A.; Ponomareva, E. E. SU 1,086,720, 1998; Chem. Abstr.
2000, 133, 252166.
1
X-ray structural data of compound 5f, H NMR and 13C
NMR spectra of compounds 2–5, 6e and 7d, preparative pro-
cedure for compounds 2, optimized geometries and energies.
Supplementary data associated with this article can be found
in the online version, at doi:10.1016/j.tet.2006.11.054.
14. (a) Reed, A.; Weinstock, R.; Weinhold, F. J. Chem. Phys. 1985,
83, 745; (b) Foster, J. P.; Weinhold, F. J. Am. Chem. Soc. 1980,
102, 7211.
References and notes
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ꢂ0.60 V (C) versus SCE.
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