Reaction of N-chloroamines with carbanions derived from ethyl acetoacetate and diethyl malonate

Article abstract of DOI:10.1134/S1070363217080072

Carbanions derived from ethyl 3-oxobutanoate and diethyl malonate reacted with an equimolar amount of N-chloro-N-ethylethanamine, N-chloromorpholine, or N-chloropiperidine to give diethyl 2,3-diacetylbutanedioate and tetraethyl ethane-1,1,2,2-tetracarboxylate in 68–83% yield. The possibility of heterocoupling of ethyl 3-oxobutanoate and diethyl malonate carbanions by the action of N-chloro-N-ethylethanamine and the effect of the molar reactant ratio on the selectivity of oxidative homo- and heterocoupling were studied.

Full text of DOI:10.1134/S1070363217080072

ISSN 1070-3632, Russian Journal of General Chemistry, 2017, Vol. 87, No. 8, pp. 1685–1688. © Pleiades Publishing, Ltd., 2017.
Original Russian Text © A.V. Zorin, A.T. Zainashev, V.V. Zorin, 2017, published in Zhurnal Obshchei Khimii, 2017, Vol. 87, No. 8, pp. 1271–1274.
Reaction of N-Chloroamines with Carbanions
Derived from Ethyl Acetoacetate and Diethyl Malonate
A. V. Zorin*, A. T. Zainashev, and V. V. Zorin
Ufa State Petroleum Technological University, ul. Kosmonavtov 1, Ufa, Bashkortostan, 450062 Russia
*e-mail: chemist.518@mail.ru
Received May 11, 2017
Abstract—Carbanions derived from ethyl 3-oxobutanoate and diethyl malonate reacted with an equimolar
amount of N-chloro-N-ethylethanamine, N-chloromorpholine, or N-chloropiperidine to give diethyl 2,3-
diacetylbutanedioate and tetraethyl ethane-1,1,2,2-tetracarboxylate in 68–83% yield. The possibility of
heterocoupling of ethyl 3-oxobutanoate and diethyl malonate carbanions by the action of N-chloro-N-
ethylethanamine and the effect of the molar reactant ratio on the selectivity of oxidative homo- and
heterocoupling were studied.
Keywords: diethyl malonate, acetoacetic ether, α-carbanions, metallation, oxidative homo- and heterocoupling,
N-chloroamines
DOI: 10.1134/S1070363217080072
Reactions of α-carbanions derived from carboxylic
acids and their esters with various aminating agents
[N-haloamines, O- and N-substituted hydroxylamines,
oxaziridines, O-(arenesulfonyl) ketone oximes, arene-
diazonium salts, azides, dialkyl azodicarboxylates,
1-chloro-1-nitrosocycloalkanes, N-(4-methylbenzenesulfo-
nyl)iminophenyl-λ3-iodane, etc.] provide a nontrivial
and attractive synthetic approach to α-amino acids [1].
dioate (4a) and tetraethyl ethane-1,1,2,2-tetracar-
boxylate (4b), respectively, in 68–83% yield (Scheme 1,
Table 1).
1
Compounds 4a and 4b were identified by H and
13C NMR and mass spectra. Their spectral parameters
satisfactorily coincided with those given in [5, 6].
Diethyl 2,3-diacetylbutanedioate (4a) was isolated as a
mixture of meso and rac diastereoisomers at a ratio of
1
The reaction of chloramine (NH2Cl) with metalated
carboxylic acids in tetrahydrofuran at –50°C was
reported to give the corresponding α-amino acids in a
very low yield [2, 3]. However, carbanions generated
by metalation of diethyl malonate and its substituted
derivatives reacted with chloramine to produce 72–
90% of diethyl 2-aminomalonates [4]. In view of the
above stated, study of the synthetic potential of this
reaction, in particular with participation of N-chloro-
dialkylamines attracts interest.
~1:5 (according to the H and 13C NMR and mass
spectral data). Signals in the 13C NMR spectra were
assigned to meso and rac diastereoisomers with account
taken of published data [7, 8]. As follows from the data
in Table 1, the reaction of N-chloro amines 3a–3c with
diethyl malonate carbanion 2b was more efficient. The
best yield of tetraethyl ethane-1,1,2,2-tetracarboxylate
(4b) was attained with the use of N-chloromorpholine
(3b). Analysis of our results and published data [5, 9,
10] suggests that oxidative homocoupling of metalated
ethyl acetoacetate or diethyl malonate by the action of
N-chloro amines 3a–3c is analogous to the reactions of
the same substrates with iodine or alkyl hypochlorites.
We have found that carbanions 2a and 2b generated
from ethyl 3-oxobutanoate (1a) and diethyl malonate
(1b) by the action of sodium ethoxide in diethyl ether
under argon react with an equimolar amount of
N-chloro-N-ethylethanamine (3a), N-chloroporpholine
(3b), or N-chloropiperidine (3c) at room temperature
(reaction time 2 h) to give the corresponding oxidative
homocoupling products, diethyl 2,3-diacetylbutane-
We presumed that both homo- and hereocoupling
products could be formed simultaneously in the
reaction of a mixture of ethyl 3-oxobutanoate and di-
ethyl malonate carbanions with N-chloro amines. The
possibility of heterocoupling was studied using
1685

1686
ZORIN et al.
Scheme 1.
O
O
O
O
O
O
O
_
C
H
O
O
O
Na+
2a
O
O
4a
R
Cl
3
1a
EtONa
O
O
O
O
O
O
O
O
_
C
H
O
O
O
O
O
O
O
O
1b
Na+
2b
4b
R = Et2N (a), morpholin-4-yl (b), piperidin-1-yl (c).
Scheme 2.
Cl
O
O
O
N
O
O
O
2a
4a
+ 2b
+ 4b +
O
5
N-chloro-N-ethylethanamine; we also examined the
effect of the molar reactant ratio on the selectivity for
homo- and heterocoupling products.
Similar results were obtained previously in the
oxidative coupling of lithium derivatives of carboxylic
acids by the action of tert-butyl hypoiodite [11], iodine
[12], 1,2-dibromoethane [13], tetrachloro- [14] and
tetrabromomethanes [15], and N-chloro- and N-bromo-
N-ethylethanamines [16].
The reaction of an equimolar mixture of carbanions
2a and 2b with N-chloro amine 3a (molar ratio
1a:1b:3a = 1:1:2) at 20–25°C in 2 h afforded a
mixture of homo- and heterocoupling products 4a, 4b,
and 5 in an overall yield of 79% (Scheme 2). The
product ratio depended on the molar ratio 2a/2b, so
that the selectivity for heterocupling product 5 can be
varied (Table 2).
Thus, no amination products are formed in the
reactions of carbanions 2a and 2b with N-chloro-
dialkylamines, but oxidative coupling of 2a and 2b
occurs instead.
Table 2. Ratios of homo- and heterocoupling products in the
reaction of mixtures of ethyl 3-oxobutanoate and diethyl
malonate carbanions 2a and 2b with N-chloro-N-ethyl-
ethanamine (3a)a
Table 1. Oxidative homocoupling of ethyl 3-oxobutanoate
and diethyl malonate carbanions 2a and 2b with N-chloro-
amines 3a–3ca
Yield, %
N-Chloroamine
Product ratio, %
2a : 2b
4a
68
74
72
4b
75
83
80
4a
17
52
69
4b
67
21
21
5
3а
3b
3c
1 : 1
2 : 1
4 : 1
16
27
10
a
Ratio 2:3 = 1:1, diethyl ether, 20–25°C, inert atmosphere
a
Diethyl ether, 20–25°C, inert atmosphere (argon), reaction time 2 h.
(argon), reaction time 2 h.
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REACTION OF N-CHLOROAMINES WITH CARBANIONS
1687
EXPERIMENTAL
[M]+, 198 (14), 173 (28), 167 (16), 145 (15), 128 (9),
127 (50), 117 (12), 99 (31), 97 (9), 43 (100).
The 13C NMR spectra were recorded on a Bruker
AM-300 spectrometer at 75.47 MHz using
tetramethylsilane as internal standard. The products
were analyzed by gas chromatography on a Khromatek-
Kristal 5000.2 instrument equipped with a flame
ionization detector (carrier gas helium, flow rate
1.1 mL/min; Restek RTX-5 capillary column,
30 m × 0.25 mm, film thickness 0.25 μm; oven
temperature programming from 50 to 270°C at a rate
of 10 deg/min). GC/MS analysis was performed with a
Shimadzu GCMS-QP2010S instrument (electron
impact, 70 eV; a.m.u. range 33–350; HP-1MS
capillary column, 30 m×0.25 mm, film thickness
0.25 μm; injector temperature 300°C, ion source
temperature 250°C; oven temperature programming
from 50 to 300°C at a rate of 20 deg/min; carrier gas
helium, flow rate 1.1 mL/min).
1
rac-4a. H NMR spectrum (CDCl3), δ, ppm: 1.25 t
(6H, CH3, J = 7.2 Hz), 2.42 s (6H, CH3CO), 4.15 q
(4H, CH2, J = 6.9 Hz), 4.48 s (2H, CH). 13C NMR
spectrum (CDCl3), δC, ppm: 13.73 (CH3), 30.79
(CH3CO), 57.77 (CH), 62.10 (CH2), 167.05 (COO),
201.56 (C=O). Mass spectrum, m/z (Irel, %): 258 (0.2)
[M]+, 198 (15), 173 (30), 167 (20), 145 (16), 128 (9),
127 (50), 117 (13), 99 (32), 97 (9), 43 (100).
Tetraethyl ethane-1,1,2,2-tetracarboxylate (4b).
1
mp 75°C. H NMR spectrum (CDCl3), δ, ppm: 1.27 t
(12H, CH3, J = 7.2 Hz), 4.13 s (2H, CH), 4.22 q (8H,
CH2, J = 6.9 Hz). 13C NMR spectrum (CDCl3), δC,
ppm: 13.91 (4C, CH3), 51.42 (2C, CH), 62.02 (4C,
CH2), 167.08 (4C, C=O). Mass spectrum, m/z (Irel, %):
319 (0.2) [M]+, 273 (17), 273 (18), 245 (26), 227 (30),
226 (16), 200 (19), 199 (47), 173 (33), 171 (33), 154
(19), 145 (16), 143 (47), 128 (12), 127 (100), 117 (17),
100 (10), 99 (93), 55 (12), 45 (10).
Reactions of ethyl-3-oxobutanoate and diethyl
malonate carbanions with N-chloro amines (general
procedure). Ethyl 3-oxobutanoate (1a) or diethyl
malonate (1b), 0.005 mol, was added with stirring at
20–25°C to a solution of sodium ethoxide prepared
from 0.0075 mol of sodium and 25 mL of anhydrous
ethanol. Sodium derivative 2a or 2b separated from the
solution. The mixture was evaporated to dryness, the
residue was dissolved in 30 mL of anhydrous diethyl
ether, the solution was cooled to 0–5°C, and a solution
of 0.005 mol of N-chloro amine 3a–3c in 15 mL of
diethyl ether was added. The mixture was stirred for
2 h at 20–25°C and treated with 30 mL of distilled
water, the organic phase was separated, the aqueous
phase was extracted with diethyl ether (3×30 mL), and
the extracts were combined with the organic phase,
dried over Na2SO4, and evaporated to isolate crys-
talline product 4a or 4b.
Triethyl 3-oxobutane-1,1,2-tricarboxylate (5).
13C NMR spectrum (CDCl3), δC, ppm: 13.76 (2C,
CH3), 13.95 (CH3), 29.72 (CH3), 51.07 (CH), 57.47
(CH), 61.56 (2C, CH2), 61.62 (CH2), 166.59 (3C,
COO), 202.89 (C=O). Mass spectrum, m/z (Irel, %):
256 (6), 241 (9), 195 (6), 185 (7), 183 (8), 167 (24),
165 (11), 143 (9), 142 (11), 141 (7), 124 (14), 115 (9),
53 (9), 44 (6), 43 (100).
ACKNOWLEDGMENTS
This study was performed under financial support
by the Ministry of Education and Science of the
Russian Federation in the framework of the base part
of state assignment in the sphere of research activity
(project no. 4.6451.2017/8.9).
The oxidative coupling of a mixture of ethyl-3-
oxobutanoate and diethyl malonate carbanions by
the action of N-chloro-N-ethylethanamine was carried
out in a similar way. A mixture of esters 4a, 4b, and 5
was isolated.
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