Reaction of α-carbanions of lithium acylates with 1,2-dibromoethane

Article abstract of DOI:10.1134/S1070363215060043

The reaction of 1,2-dibromoethane with α-carbanions of lithium acylates generated from acetic, butyric, isobutyric, and capronic acids with lithium diisopropylamide has been studied. Anion-radical and anionic pathways of the products formation have been discussed.

Full text of DOI:10.1134/S1070363215060043

ISSN 1070-3632, Russian Journal of General Chemistry, 2015, Vol. 85, No. 6, pp. 1382–1385. © Pleiades Publishing, Ltd., 2015.
Original Russian Text © A.V. Zorin, A.T. Zaynashev, A.R. Chanysheva, V.V. Zorin, 2015, published in Zhurnal Obshchei Khimii, 2015, Vol. 85, No. 6,
pp. 914–917.
Reaction of α-Carbanions of Lithium Acylates
with 1,2-Dibromoethane
A. V. Zorin, A. T. Zaynashev, A. R. Chanysheva, and V. V. Zorin
Ufa State Petroleum Technological University, ul. Kosmonavtov 1, Ufa, 450062 Russia
e-mail: chemist.518@mail.ru
Received February 16, 2015
Abstract—The reaction of 1,2-dibromoethane with α-carbanions of lithium acylates generated from acetic,
butyric, isobutyric, and capronic acids with lithium diisopropylamide has been studied. Anion-radical and
anionic pathways of the products formation have been discussed.
Keywords: 1,2-dibromoethane, dicarboxylic acid, enolate anion, carbanion, metalation, oxidative coupling
DOI: 10.1134/S1070363215060043
Metalated CH-acids (esters, nitriles, acylates, di-
phenylmethane, etc) are known to react with alkyl
halides and dihalides (the latter containing distant
CH2Hlg) groups via the nucleophilic substitution of the
halogen with the carbanion [1]. The interaction involv-
ing vicinal alkyl dihalide follows a more complicated
path yielding products of the halogen nucleophilic
substitution as well as of oxidative dimerization of
carbanions [1, 2]. The reaction direction depends on
structure of the carbanion, the 1,2-dihaloalkane, and
the halogen nature [1, 2].
reaction direction, the yield of the target products, and
the possible pathway of their formation.
We have earlier studied the reaction of carbanion of
lithium acetate (generated from acetic acid Ia with
lithium diisopropylamide LDA) with 1,2-dibromo-
ethane III in THF medium at 20–25°С under argon
atmosphere at the Ia : LDA : III molar ratio of 2 : 4 : 1
during 2 h [3]. The reaction yields a mixture of pro-
ducts of nucleophilic substitution of bromine with car-
banion of lithium acetate (adipic acid IV) and oxida-
tive coupling of the carbanions (succinic acid Vа).
The interaction of carbanions with 1,2-dihalo-
alkanes occurring under mild conditions with the high
product yield is of practical importance; however, its
mechanism has not been investigated so far.
The interaction of 1,2-dibromoethane with α-car-
banions of lithium acylates generated with lithium
diisopropylamide from isobutyric Ib, butyric Ic, and
capronic Id acids (under the same conditions) gave,
respectively, 2,2,3,3-tetramethylsuccinic acid Vb
(yield 37%), 2,3-diethylsuccinic acid Vc (64%), and
We studied the interaction of α-carbanions of
lithium acylates with 1,2-dibromoethane in order to
elucidate the effect of the reactants structure on the
1
2,3-dibutylsuccinic acid Vd (76%). The Н and 13C
Scheme 1.
HOOC
HOOC
COOH
Br
IV
R1
R1
R2
R1
R2
Br
Li+
(1)
2LDA
III
−
COO−Li+
COOH
Iа−Id
(2) 2H+
R1
R2
IIа−IId
COOH
R2
Vа−Vd
R1 = R2 = H (а); R1 = R2 = CH3 (b); R1 = H, R2 = C2H5 (c), C4H9 (d).
1382

REACTION OF α-CARBANIONS OF LITHIUM ACYLATES
1383
NMR spectral parameters of the products satisfactorily
coincided with the reference data [4] (Scheme 1).
1-ene X as the trap. The interaction of α-carbanions of
lithium acylates IIa–IId with 1,2-dibromoethane in the
presence of hex-1-ene yielded the dicarboxylic acids
IV and Va–Vd along with ethyl bromide IX and octyl
bromide XIII (mass spectrometry data). Compound
XII was formed via the stage of formation of the spin-
adduct XI further stabilized via hydrogen abstraction
from the solvent.
The acids Vc and Vd were formed as ≈(8–10) : 1
mixtures of the meso- and rac-diastereomers, as
1
13
followed from Н and C NMR spectroscopy as well
as chromato-mass spectrometry data.
In order to elucidate the possible reaction me-
chanism we thoroughly investigated the products
composition. Gas-liquid chromatography and mass
spectrometry studies revealed that all reaction mixtures
contained ethyl bromide IX along with the
dicarboxylic acids IV and Va–Vd. Compound IX
could be formed via the stage of electron transfer from
the α-carbanion IIa–IId to 1,2-dibromoethane III
accompanied by the formation of the lithium acylate
radical VIa–VId and the anion-radical VII.
VIII +
Br
XI
X
Br
XII
Taking into account the collected results, we
suggested the following scheme of the formation of
dicarboxylic acids Va–Vd, the formal products of
oxidative coupling of α-carbanions of lithium acylates
IIa–IId (Scheme 2).
−
.
R1(R2)CCOO−Li+ + [BrCH2CH2Br]
IIа−IId + III
VIа−VId
VII
Analysis of the gas phase of the reaction mixtures
revealed the presence of ethylene that could be formed
via bromine elimination from 2-bromoethyl radical
VIII [7] or the carbanion XIV [8, 9].
The elimination of bromide anion with anion-
radical VII to form the 2-bromoethyl radical VIII and
the stabilization of the latter via hydrogen abstraction
from the solvent finally led to ethyl bromide IX.
−
CH2CH2Br
VIII
CH2=CH2
−Br−
[H]
−Br
CH3CH2Br
VII
CH2CH2Br
XIV
−Br−
IX
Electrophilic transfer of bromine from 1,2-di-
bromoethane to α-carbanion of the lithium acylates
IIa–IId could be suggested yielding lithium salts of α-
bromocarboxylic acids; the latter were further involved
VIII
The formation of the 2-bromoethyl radical was
confirmed using the spin trap method [5, 6] with hex-
Scheme 2.
R1(R2)CCOO−Li+ + [BrCH2CH2Br]
−
.
Iа−Id + III
VIа−VId
VII
R1
R2
O−Li+
O−Li+
R1
R2
C
Li+−OC(O)
IIа−IId + VIа−VId
+ III −VII
R1
R2
R1
R1
R1
R2
2H+
COO−Li+
COOH
Li+−OC(O)
(O)
2VIа−VId
HOC
R2
R2
Vа−Vd
XIIIа−XIIId
[H]
VIа−VId
CH3CH2Br
CH2CH2Br
VIII
− Br−
IX
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 85 No. 6 2015

1384
ZORIN et al.
Yield of products of oxidative coupling and nucleophilic
substitution in the reactiona of α-carbanions of lithium
acylates IIa–IId with 1,2-dibromoethane III
Hence, even though the anion-radical mechanism of
the studied reaction was more plausible, the collected
data did not allow for the unambiguous pathway
elucidation.
Product of
oxidative
coupling
Product of
nucleophilic
substitution
Starting
compound
Yield,
%
Yield,
%
Analysis of the yields of the dicarboxylic acids led
to a conclusion that the interaction with 1,2-dibromo-
ethane was the most efficient in the cases of the
carbanions IIc–IId containing the anionic site at the
secondary α-carbon atom. Yield of the dicarboxylic
acids from the carbanions IIa, IIb was noticeably
lower (see the table).
Ia
Ib
Ic
Id
Va
Vb
Vc
Vd
40
37
64
76
IV
–
–
38
–
–
–
–
To summarize, the interaction of carbanions with
1,2-dibromoethane can be used for preparation of
dicarboxylic acids under mild conditions with satis-
factory yields.
in formation of dicarboxylic acids Va–Vd via nucleo-
philic substitution of bromine assisted by the corres-
ponding compound IIa–IId.
1
2
–
¯
BrCH2CH2Br + IIа–IId →CH2CH2Br + R (R )C(Br)COO ,
EXPERIMENTAL
2H+
R1(R2)C(Br)COO– + IIа–IId → XIIIа–XIIId
Vа–Vd.
NMR spectra of the solutions in a СDCl3–
CF3COOH mixture were recorded using a Bruker AM-
300 [300 (1Н) and 75.47 (13С) MHz] with TMS re-
ference. Chromato-mass spectral analysis was per-
formed using a GCMS-QP2010S Shimadzu instrument
(EI at 70 eV). An HP-1MS capillary column (30 m ×
0.25 mm × 0.25 µm) was used, the vaporizer
temperature was 280°C, the ionization chamber tem-
perature was 200°C. The analysis was carried out at
heating from 50 to 280°C at a rate 10 deg/min using
helium (1.1 mL/min) as carrier gas. Elemental analysis
was performed using an Hekatech Euro EA 3000
СHNS/O analyzer.
The transfer of electrophilic bromine to anionic
reactive site is a known trans-metalation reaction
[10–17]. However, this process is exclusively possible
when it is thermodynamically favorable, like in the
case of the interaction of 1,2-dibromoethane with di-
carbanions [15].
The possibility of electrophilic bromine transfer from
1,2-dibromoethane to the α-carbanion of lithium acylate
IIa–IId seems unlikely, as follows from the com-
parison of pKa values of alkanes and acylates (40–42
and 24 [18], respectively) reflecting their СН-acidity
and the carbanions proton affinity correlated to the
halogen affinity [19].
Reaction of carboxylic acids with 1,2-dibromo-
ethane. A solution of 0.02 mol of lithium diisopropyl-
amide in 30 mL of anhydrous THF was cooled to 0–5°С
under argon, and a solution of 0.01 mol of carboxylic
acid Ia–Id in 20 mL of anhydrous THF was added
dropwise at stirring. The reaction mixture was heated
to 35–40°С and stirred during 30–40 min. The mixture
was then cooled to 20–25°С, a solution of 0.005 mol
of 1,2-dibromoethane in 20 mL of anhydrous THF was
added, and the resulting mixture was stirred during 2 h.
A gas was evolved in the course of the reaction; it was
passed through a solution of bromine in tetrachloro-
methane to test for the presence of ethylene. 30 mL of
distilled water was then added to the reaction mixture.
The aqueous layer was treated with 10 wt % HCl
solution till pH 1; the reaction products were extracted
with diethyl ether (3 × 30 mL). The combined extracts
were dried over MgSO4. After the ether removal,
crystalline dicarboxylic acids IV and Va–Vd were
The appearance of the carbanion XIV in the re-
action could be confirmed by the formation of octyl
bromide from hex-1-ene involving that carbanion [11].
Aklyllithium compounds could be prepared via
direct interaction of alkyl chlorides or alkyl bromides
with lithium metal [11, 20–21]. In view of that, we
investigated the possibility of formation of octyl
bromide under the similar condition via generation of
2-bromoethyl carbanion XIV from 1,2-dibromoethane
with lithium [20] in the presence of hex-1-ene.
Noteworthily, the interaction of alkyl bromides with
lithium could occur via a single-electron transfer
giving the anion-radical VII and the radical VIII [11].
Mass spectrometry study revealed that under the
described conditions only traces of octyl bromide were
formed in the reaction mixture.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 85 No. 6 2015

REACTION OF α-CARBANIONS OF LITHIUM ACYLATES
1385
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anhydrous THF was added dropwise under argon at
stirring to a solution of 0.01 mol of lithium
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ACKNOWLEDGMENTS
This work was financially supported by the Ministry
of Education and Science of the Russian Federation in
the frame of the basic part of the governmental
contract (project no. 49).
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