Reactions of diethyl dibromomalonate and ethyl 2,2-dichloroacetoacetate with water and carbonyl compounds (aldehydes and ketones) in the presence of pentacarbonyliron

Article abstract of DOI:10.1023/B:RUJO.0000045179.42952.58

Diethyl dibromomalonate and ethyl 2,2-dichloroacetoacetate are effectively reduced with the system pentacarbonyliron-proton-donor compound (water or butyl methyl ketone) to give the corresponding hydrodehalogenation products. These results provide a support for the previous assumption that the key reaction stage is reduction with pentacarbonyliron of initially formed radical to anion which is then involved in proton transfer.

Full text of DOI:10.1023/B:RUJO.0000045179.42952.58

Russian Journal of Organic Chemistry, Vol. 40, No. 7, 2004, pp. 924–927. Translated from Zhurnal Organicheskoi Khimii, Vol. 40, No. 7, 2004,
pp. 965–967.
Original Russian Text Copyright © 2004 by Terent’ev, Vasil’eva, Mysova, Chakhovskaya.
Reactions of Diethyl Dibromomalonate
and Ethyl 2,2-Dichloroacetoacetate with Water and Carbonyl
Compounds (Aldehydes and Ketones) in the Presence
of Pentacarbonyliron
A. B. Terent’ev, T. T. Vasil’eva, N. E. Mysova, and O. V. Chakhovskaya
Nesmeyanov Institute of Organometallic Compounds, Russian Academy of Sciences,
ul. Vavilova 28, Moscow, 117813 Russia
e-mail: terent@ineos.ac.ru
Received June 28, 2003
Abstract—Diethyl dibromomalonate and ethyl 2,2-dichloroacetoacetate are effectively reduced with the
system pentacarbonyliron–proton-donor compound (water or butyl methyl ketone) to give the corresponding
hydrodehalogenation products. These results provide a support for the previous assumption that the key
reaction stage is reduction with pentacarbonyliron of initially formed radical to anion which is then involved in
proton transfer.
differing in their proton-donor power) in the presence
of Fe(CO)5. Two main processes occurred: reduction
with replacement of one or two halogen atoms by
hydrogen and (in the presence of carbonyl compounds)
Reformatsky-type addition. The relative contributions
of these processes are determined by the reaction
conditions, the nature of reactants, and their ratio
(see table).
In the recent years, Barbier–Reformatsky-type
reactions have attracted persistent interest [1, 2]. We
previously showed that pentacarbonyliron is an effec-
tive promotor of Reformatsky-type reactions, i.e., reac-
tions of halogen-substituted carboxylic acid esters
[3, 4] and nitriles [5], as well of allyl and alkyl halides
[6], with aldehydes and ketones. A number of the
examined reactions are characterized by high selec-
tivity and good yields (up to 90%), and they do not
require inert atmosphere and anhydrous medium.
Therefore, they can be successfully used for prepara-
tive purposes. However, despite a great deal of avail-
able experimental data, the character of particular
stages in the mechanism of such reactions with
participation of Fe(CO)5 remains unclear. For example,
some reactions are accompanied by reduction of the
organohalogen substrate with replacement of the halo-
gen atom by hydrogen; the contribution of this process
depends on the reaction conditions. The reduction of
polychlorinated alkanes with the system Fe(CO)5–
proton donor (2-propanol, silanes) was described
previously [7], but it was not observed in Reformatsky
reactions even under electrochemical conditions [8].
In the recent time, much attention is given to
ecologically safe procedures for performing organic
reactions in water [9, 10]. The reaction of ester I with
Fe(CO)5 (in the absence of water and carbonyl
compound) leads to formation of a mixture of almost
equal amounts of diethyl bromomalonate (Ia) and di-
ethyl malonate (Ib) in an overall yield of 57%, i.e., the
reduction occurs via abstraction of hydrogen atoms
from the substrate itself. When the reaction was carried
out with excess water as proton donor, ester I was
reduced to Ib almost quantitatively. By decreasing the
concentration of Fe(CO)5 and water we succeeded in
obtaining mainly partial reduction product Ia (65% of
the overall yield). In the reaction of dibromomalonate I
with butyl methyl ketone (III) we obtained addition
product C4H9C(CH3)=C(COOC2H5)2 (V) (via Refor-
matsky-type reaction followed by elimination of water
molecule) and a large amount of ester Ib (43%).
Presumably, the latter originates from the presence of
In the present work we examined reactions of di-
ethyl dibromomalonate (I) and ethyl 2,2-dichloroaceto-
acetate (II) with water, butyl methyl ketone (III), and
benzaldehyde (IV) (i.e., with compounds essentially
1070-4280/04/4007-0924 © 2004 MAIK “Nauka/Interperiodica”

REACTIONS OF DIETHYL DIBROMOMALONATE
925
Reduction of diethyl dibromomalonate and ethyl 2,2-dichloroacetoacetate with water and addition to carbonyl compounds in
the presence of Fe(CO)5
Initial reactants
RCXO (1 mmol) Fe(CO)5
Products (yield, %)
Run no.
ester (1 mmol)
I or II
adduct
Ia or IIa
Ib or IIb
H2O, mmol
01
02
5
–
–
2
–
–
–
a40a
89
14
I
I
.52.5
.50.7
07
03
04
05
06
07
08
09
–
–
–
5
–
5
5
–
III
IV
–
2
–
–
–
28
30
–
32
–
25
08
43
–
I
2
I
2
2
–
I
05
65
31
64
40
II
II
II
II
–
2
–
–
–
1
18
30
–
–
.50.7
–
–
–
10
11
12
13
5 + DMF, 4
2
2
2
2
–
40
31
75
70
16
–
II
II
II
II
–
–
–
–
b61b
b17b
–
III
IV
III
IV
–
a
65% of the overall yield.
Unreacted III or IV.
b
which either adds at the C=O bond of benzaldehyde
within iron carbonyl complex C, resulting in formation
of adduct VI via elimination of OH–Br species or
abstracts a proton from proton donor (water or ketone),
yielding monobromomalonate Ia.
proton-donor groups in molecule III. As might be
expected, in the reaction with benzaldehyde (IV),
where abstraction of only neutral (radical) hydrogen
species is possible, the contribution of the reduction
process was insignificant, and the major product was
unsaturated compound VI. With dichloroacetoacetate
II as substrate, only the reduction to the corresponding
monochloro derivative IIa occurred in all cases, but
the yield of IIa strongly depended on the conditions.
No Reformatsky reaction products were detected. In
the presence of water and butyl methyl ketone (which
are fairly strong proton donors), one chlorine atom in
II was replaced by hydrogen, and ester IIa was selec-
tively formed in a good yield (65–70%). Interestingly,
ester IIa was also obtained in a high yield (75%) in
the reaction of II with benzaldehyde (IV). Probably,
benzaldehyde acts as an efficient donor of atomic
hydrogen, and the reaction follows a radical scheme.
We believe that in the first stage pentacarbonyliron
reacts with ester I to give radical A:
Fe(CO)5
A
[BrC(COOEt)2]
B
PhCHO
–HOBr
PhCH C(COOEt)2
VI
H+
BrCH(COOEt)2
Ia
X
O
Fe
C
H
C
C
Fe(CO)5
·
Br2C(COOEt)2
BrC(COOEt)2
On the other hand, radical A is capable of directly
adding at the C=O bond of aldehyde or ketone with
subsequent formation of the corresponding alcoholate;
however, this version contradicts the results of our
previous kinetic studies [4].
I
A
Radical A can react further along two pathways.
The first of these includes reduction of A to anion B
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 40 No. 7 2004

TERENT’EV et al.
926
Our experimental data show that the contribution of
Reaction of diethyl dibromomalonate and ethyl
2,2-dichloroacetoacetate with carbonyl compounds
in the presence of pentacarbonyliron. A mixture of
required amounts (see table) of halogenated ester I or
II, carbonyl compound III or IV, water, and Fe(CO)5
was dissolved in 2 ml of benzene, and the solution was
heated for 3–4 h at 80°C. The mixture was diluted with
2 ml of benzene and treated with 1 N hydrochloric
acid, and the organic phase was washed with water and
dried over MgSO4. The products were isolated by pre-
parative GLC or TLC (petroleum ether–chloroform–
ethyl acetate, 8:1:1). The yields were determined by
GLC using authentic samples as reference. The results
are collected in table.
the reduction process increases in the presence of
proton donors (water, butyl methyl ketone) and that it
is much lesser in the presence of benzaldehyde, i.e.,
initial reduction of radical A to anion B is the most
probable. In the presence of excess water (see table,
run no. 1), diethyl dibromomalonate is reduced with
almost quantitative replacement of both halogen atoms
by hydrogen while in the absence of water (run no. 3)
the yield of the reduction product is twice as low
(hydrogen atoms of the substrate are involved).
Analogous relations are observed in the reactions with
benzaldehyde and butyl methyl ketone: here, the yields
of the adducts are approximately equal (run nos. 4, 5),
but the contribution of the reduction process in the
presence of butyl methyl ketone (run no. 5) is several
times greater than in the reaction with benzaldehyde
(run no. 4). This means that the reaction also involves
reduction of radical A to anion B. A similar pattern is
typical of the reaction with ethyl 2,2-dichloroaceto-
acetate. In the presence of excess water, the yield of
ethyl 2-chloroacetoacetate is 65%, while in the absence
of water, only 31% (run nos. 6, 7). It should be noted
that the contributions of the reduction process in the
presence of both benzaldehyde and butyl methyl
ketone (run nos. 12, 13) are almost equal (70–75%).
Presumably, the rate of the reaction of radical A with
benzaldehyde, which is an efficient donor of atomic
hydrogen, considerably exceeds the rate of its reduc-
tion into anion B, provided that concurrent addition
process is lacking.
1
Diethyl bromomalonate (Ia). H NMR spectrum,
δ, ppm: 1.25 t (3H, CH3CH2, J = 8 Hz), 4.23 q (2H,
CH2, J = 6 Hz), 4.77 s (1H, CH). 13C NMR spectrum,
δC, ppm: 165.4 (COO), 63.8 (CH2O), 43.0 (CHBr),
14.5 (CH3). Mass spectrum, m/z (Irel, %): 238 [M]+ (5),
193 [M – OEt]+ (15), 166 [CH2BrCO2Et]+ (30), 138
[M – C2H3 – CO2Et]+ (75), 122 [CH2BrCO]+ (20), 29
[Et]+ (100). Found, %: C 35.7; H 4.8; Br 33.3.
C7H11BrO4. Calculated, %: C 35.2; H 4.6; Br 33.4
Diethyl benzylidenemalonate (VI). Mass spec-
trum, m/z (Irel, %): 248 [M]+ (57), 219 [M – Et]+ (20),
203 [M – OEt]+ (90), 175 [M – COOEt]+ (22), 174
[M – HCOOEt]+ (30), 158 [M – 2OEt]+ (80), 130
[M – COOEt – OEt]+ (58), 102 [M – 2COOEt]+ (100),
77 [C6H5]+ (30).
Diethyl (1-methylpentylidene)malonate (V).
Yield 30%. Mass spectrum, m/z (Irel, %): 242 [M]+
(20), 197 [M – OEt]+ (40), 196 [M – HOEt]+ (20), 150
[M – 2HOEt]+ (100), 122 [M – HCOOEt – HOCEt]+
(20), 99.
EXPERIMENTAL
1
The H and 13C NMR spectra were recorded on
1
Ethyl 2-chloroacetoacetate (IIa). H NMR spec-
a Bruker WP-200 spectrometer (200 MHz) using
CDCl3 as solvent; the chemical shifts were measured
relative to tetramethylsilane. The mass spectra were
obtained on a Finnigan Mat Magnum GC–MS system
using an Ultra-2 capillary column (25 m); oven tem-
perature programming from 30 to 220°C at 2.5°C/min.
GLC analysis was performed on an LKhM-80 chro-
matograph equipped with a thermal conductivity
detector and a 1300×3-mm steel column packed with
15% of SKTFT-50Kh on Chromaton N-AW; carrier
gas helium, flow rate 60 cm3/min; oven temperature
programming from 50 to 250°C (6 deg/min). All
organic reagents were purified by distillation; Fe(CO)5
from Fluka (purity 97%) was used without additional
purification.
trum, δ, ppm: 1.25 t (3H, CH3CH2, J = 8 Hz), 2.32 s
(3H, CH3CO), 4.23 q (2H, CH2, J = 6 Hz), 4.71 s (1H,
CH). 13C NMR spectrum, δC, ppm: 197.0 (C=O), 165.5
(COO), 63.6 and 61.9 (CH2O), 62.5 (CHCl), 26.7
(CH3CO), 14.6 (CH3CH2). Mass spectrum, m/z
(Irel, %): 164 [M]+ (10), 122 [M – CH2=CO]+ (75), 94
[M – CH2CO – C2H4]+ (72), 76 [CHCl=CO]+ (28), 43
[CH3CO]+ (100), 29 [Et]+ (74). Found, %: C 44.3;
H 5.6; Cl 20.3. C6H9ClO3. Calculated, %: C 43.7;
H 5.5; Cl 21.6.
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