Condensation of trifluoromethanesulfonamide with paraformaldehyde and oxamide

Article abstract of DOI:10.1134/S1070428010100052

Depending on the conditions, three-component condensation of trifluoromethanesulfonamide with paraformaldehyde and oxamide led to the formation of linear products, N-mono- and N,N'-bis[(trifluoromethylsulfonyl) aminomethyl]oxamide, bis[(trifluoromethylsulfonyl)aminomethyl] ethanedioate, as well as of hydrolysis and cyclization product, N-(4,5-dioxo-1,3-oxazolidin-3- ylmethyl)trifluoromethanesulfonamide.

Full text of DOI:10.1134/S1070428010100052

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2010, Vol. 46, No. 10, pp. 1471–1475. © Pleiades Publishing, Ltd., 2010.
Original Russian Text © V.I. Meshcheryakov, M.Yu. Moskalik, I. Starke, B.A. Shainyan, 2010, published in Zhurnal Organicheskoi Khimii, 2010, Vol. 46,
No. 10, pp. 1467–1471.
Condensation of Trifluoromethanesulfonamide
with Paraformaldehyde and Oxamide
V. I. Meshcheryakova, M. Yu. Moskalika, I. Starkeb, and B. A. Shainyana
a Favorskii Irkutsk Institute of Chemistry, Siberian Division, Russian Academy of Sciences,
ul. Favorskogo 1, Irkutsk, 664033 Russia
e-mail: bagrat@irioch.irk.ru
b Chemisches Institut der Universität Potsdam, P.O. Box 691553, Potsdam, D-14415 Germany
Received March 30, 2010
Abstract—Depending on the conditions, three-component condensation of trifluoromethanesulfonamide with
paraformaldehyde and oxamide led to the formation of linear products, N-mono- and N,N′-bis[(trifluoromethyl-
sulfonyl)aminomethyl]oxamide, bis[(trifluoromethylsulfonyl)aminomethyl] ethanedioate, as well as of hydrol-
ysis and cyclization product, N-(4,5-dioxo-1,3-oxazolidin-3-ylmethyl)trifluoromethanesulfonamide.
DOI: 10.1134/S1070428010100052
We previously studied the condensation of tri-
fluoromethanesulfonamide CF3SO2NH2 with para-
formaldehyde and three-component condensations of
trifluoromethanesulfonamide with paraformaldehyde
and various amides. Depending on the conditions,
these reactions led to the formation of various linear
and cyclic products [1–4]. In particular, the results of
condensations of dicarboxylic acid amides of the
general formula H2NCO(CH2)nCONH2 as amide com-
ponent with paraformaldehyde and trifluoromethane-
sulfonamide were determined by the number of meth-
ylene groups in the initial amide. When n = 1, the
product was spirocyclic 4,10-bis(trifluoromethylsul-
fonyl)-2,4,8,10-tetraazaspiro[5.5]undecane-1,7-dione
[3], while amides possessing two methylene groups
(n = 2) gave rise to either linear N,N-bis[(trifluoro-
methylsulfonyl)aminomethyl]succinamide or hetero-
cyclization product, N-[(trifluoromethylsulfonyl)-
aminomethyl]succinimide, depending on the condi-
tions [4]. In the present work we examined the three-
component condensation of sulfonamide I with para-
formaldehyde and the simplest dicarboxylic acid
amide, oxamide (II, n = 0). We expected formation of
linear condensation products at one (III) or both amide
groups (IV) and, probably (by analogy with our pre-
vious results), heterocyclization products.
Scheme 1.
O
H
H
N
N
CF3SO2NH2
+
CH2O
+
(CONH2)2
H2N
SO2CF3
O
I
II
III
O
O
H
H
N
H
N
F3CSO2
N
F3CSO2
O
+
+
N
N
H
SO2CF3
N
H
O
SO2CF3
H
O
O
IV
V
O
O
F3CSO2
SO2CF3
H
+
+
N
H
N
N
H
SO2CF3
O
N
VI
VII
1471

MESHCHERYAKOV et al.
1472
The reaction was carried out in concentrated sul-
in the region 3020–3120 cm–1 (intermolecular hydro-
gen bond). These data are consistent with the low-fre-
quency shift of the νNH band of trifluoromethanesul-
fonamide fragment upon formation of intermolecular
hydrogen bond, as reported in [5]. The IR spectrum of
V also contained an absorption band at 1722 cm–1 due
to asymmetric stretching vibrations νas(C=O) of the
dicarbonyl fragment, whereas the corresponding sym-
metric vibrations νs(C=O) were active in the Raman
spectrum (1672 cm–1).
furic acid or in ethyl acetate in the presence of sulfuric
acid. As we showed previously, different condensation
products can be formed in these media [2]. In fact, by
varying the conditions, we succeeded in isolating
N-[(trifluoromethylsulfonyl)aminomethyl]oxamide
(III), N,N′-bis[(trifluoromethylsulfonyl)aminomethyl]-
oxamide (IV), bis[(trifluoromethylsulfonyl)amino-
methyl] ethanedioate (V), and heterocyclization prod-
uct, N-(4,5-dioxo-1,3-oxazolidin-3-ylmethyl)trifluoro-
methanesulfonamide (VI) (Scheme 1). In addition,
N,N′-methylenedi(trifluoromethanesulfonamide) (VII)
and oxamide hydrolysis and alcoholysis products (in
the reaction carried out in ethyl acetate), oxalic acid
and diethyl oxalate, were detected. The products were
separated by column chromatography on silica gel, and
their structure was determined on the basis of their IR,
In the mass spectra of III–V we observed charac-
teristic fragment ion peaks with m/z 162 (CF3SO2NH-
CH2), 133 (CF3SO2), 78 (NSO2), and 69 (CF3).
The structure of heterocyclic compound VI is
1
confirmed by the presence in its H NMR spectrum of
signals from two nonequivalent methylene groups and
a very broad NH signal. The 13C NMR spectrum of VI
contained two signals from methylene carbon atoms
(δC 50 and 76 ppm) [1], two carbonyl carbon signals,
and a quartet from the CF3 group, and one signal was
observed in the 19F NMR spectrum of this compound.
Two carbonyl stretching vibrations bands (νC=O 1736
and 1812 cm–1) and one νNH band at 3200 cm–1 were
present in the IR spectrum of VI. The NCH2N and
1
Raman, and H and 13C NMR spectra. Monosubstitut-
1
ed product III displayed in the H NMR spectrum
a doublet from methylene protons and four NH signals
with equal intensities: two singlets due to primary
amino group CONH2, a triplet from the secondary
amide group, and a broadened singlet due to sulfon-
amide group, the latter being located most downfield.
The 13C NMR spectrum of III, apart from signals
belonging to the methylene carbon atom and CF3
group (quartet), contained two signals typical of amide
carbonyl carbon atoms. Unlike compound III, in the
1H NMR spectrum of symmetric disubstitution product
IV we observed a signal from the methylene protons
and two NH signals, one of which being a triplet
(NHCO), and the other, a broadened singlet (NHSO2).
Correspondingly, the 13C NMR spectrum of IV con-
tained signals from the CH2 and CF3 groups and only
one signal due to amide carbonyl carbon atom. Despite
formally symmetric structure, compound V showed in
the 1H NMR spectrum two signals from nonequivalent
NH protons as broadened singlets with equal intens-
ities (1H) at δ ~10 and 13 ppm. The IR and Raman
spectra indicated that one NH proton in structure V is
involved in intramolecular hydrogen bond and that the
other NH proton participates in intermolecular hydro-
gen bond. This followed from the presence in the IR
spectrum of a narrow peak at 3314 cm–1 (νNH, intra-
molecular hydrogen bond) and a broadened νNH band
1
OCH2N proton signals in the H NMR spectrum were
1
assigned on the basis of the H–13C HSQC spectrum
[6], where δ/δC cross peaks were observed at 5.45/76
and 4.86/50 ppm. The molecular ion peak of VI was
detected only in the negative ion mass spectrum, and
its relative intensity was as low as 2%. Fragmentation
of the molecular ion of VI involves cleavage of the
CH2–NH bond with charge localization on the tri-
fluoromethanesulfonamide fragment. The precise
m/z value of the [M + Na]+ ion in the TOF ESI
mass spectrum of VI corresponds to the formula
C5H5F3N2NaO5S, which is consistent with the assumed
structure.
The ratio of the condensation products strongly
depends on the reaction conditions. When the reaction
was carried out in ethyl acetate in the presence of
sulfuric acid, after removal of compound VII and
unreacted trifluoromethanesulfonamide by washing the
reaction mixture with diethyl ether–hexane (1:6) and
of diethyl oxalate by distillation, we isolated com-
pounds IV and VI at a ratio of ~6:1. By carrying out
the condensation in sulfuric acid at room temperature
we succeeded in raising the yield of heterocyclic prod-
uct VI and isolating monosubstituted compound III. In
this case the ratio VI:III was 3:1. Compound III was
formed as the major product in the condensation of
O
F3CSO2
O
H
N
O
H
O
N
·
·
·
SO2CF3
V
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 10 2010

CONDENSATION OF TRIFLUOROMETHANESULFONAMIDE
1473
Scheme 2.
O
H
N
H
CF3SO2NH2
N
IV
HO
HO
N
H
SO2CF3
O
O
CH2O, H+
H
H
N
N
H2N
SO2CF3
O
O
SO2CF3
III
N
N
H
VI
–NH4
H2N
HO
trifluoromethanesulfonamide with paraformaldehyde
and oxamide in sulfuric acid when the reaction time
was 40 min (room temperature). Under more severe
conditions, i.e., in sulfuric acid at elevated tempera-
ture, the major product was oxazolidinedione VI.
However, when a mixture of oxamide and trifluoro-
methanesulfonamide in sulfuric acid was preliminarily
heated until complete dissolution and paraformalde-
hyde was then added, we obtained bis[(trifluorometh-
ylsulfonyl)aminomethyl] ethanedioate (V).
Q-TOFmicro mass spectrometer (Waters, Manchester,
UK); a sample (20 μl/min) was introduced with the aid
of a Harvard syringe pump (capillary entrance voltage
3.2 kV, cone voltage 20–25 V). The elemental com-
position was determined by measuring the precise
molecular weight with an accuracy of ±3 ppm using
H3PO4 as reference. The progress of reactions was
monitored by TLC on silica gel 60 F-254 plates using
hexane–diethyl ether (1:2) as eluent.
Condensation of trifluoromethanesulfonamide
with paraformaldehyde and oxamide in ethyl
acetate–sulfuric acid. Oxamide, 2 g (22 mmol), tri-
fluoromethanesulfonamide, 7.45 g (50 mmol), and
paraformaldehyde, 1.5 g (50 mmol), were mixed with
42 ml of ethyl acetate, and 14 ml of 92% sulfuric acid
was added dropwise. The mixture was stirred for
2 days at room temperature, poured into a mixture of
ice with sodium chloride, and extracted with ethyl
acetate (3×70 ml). The extract was dried over MgSO4,
the solvent was distilled under reduced pressure, and
the residue (~9 g) was washed with a mixture of di-
ethyl ether–hexane (1:6) to remove unreacted tri-
fluoromethanesulfonamide and N,N′-methylenedi(tri-
fluoromethanesulfonamide) (~6.4 g). Diethyl oxalate
was removed from the residue by vacuum distillation.
The still residue (~900 mg) contained (according to the
1H and 13C NMR data) 50% of diethyl oxalate, 40%
of N,N′-bis[(trifluoromethylsulfonyl)aminomethyl]-
oxamide (IV), and 10% of N-(4,5-dioxo-1,3-oxazoli-
din-3-ylmethyl)trifluoromethanesulfonamide (VI). By
column chromatography (diethyl ether–hexane, 1:2;
diethyl ether) we isolated 300 mg of compound VI and
50 mg of IV.
These findings led us to conclude that monosub-
stitution product III is formed initially. The subsequent
hydroxymethylation of III with paraformaldehyde
either at the primary amide group, followed by con-
densation with the second trifluoromethanesulfon-
amide molecule, or at the secondary amide group,
followed by heterocyclization, yields disubstitution
product IV or 3-substituted 4,5-dioxo-1,3-oxazolidine
VI, respectively (Scheme 2). Compound VI was also
obtained as the major product by heterocyclization of
oxamide with paraformaldehyde and N,N′-methylene-
di(trifluoromethanesulfonamide) (VII) prepared by
condensation of trifluoromethanesulfonamide with
paraformaldehyde [1].
EXPERIMENTAL
The IR spectrum of compound V was recorded on
a Bruker Vertex 70 spectrometer with Fourier trans-
form, and the Raman spectrum of V was obtained on
a Varian 3100 FT-IR instrument. The NMR spectra
were measured on a Bruker DPX-400 spectrometer at
400 (1H), 100 (13C), and 376 MHz (19F); the chemical
shifts were determined relative to tetramethylsilane
(1H, 13C) and CCl3F (19F). The mass spectra (electron
impact, 70 eV) were recorded on a Trace DSQ II
instrument (Thermo Fisher Scientific GmbH, Dreieich,
Germany) with direct sample admission into the ion
source. The high-resolution mass spectrum (positive
electrospray ionization) was obtained on a Micromass
Condensation of trifluoromethanesulfonamide
with paraformaldehyde and oxamide in sulfuric
acid. a. A mixture of 2 g (22 mmol) of oxamide and
1.5 g (50 mmol) of paraformaldehyde was added to
7.45 g (50 mmol) of trifluoromethanesulfonamide in
95% sulfuric acid. The mixture was stirred for 2 days
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 10 2010

MESHCHERYAKOV et al.
1474
at room temperature, poured into a mixture of ice with
sodium chloride, and extracted with diethyl ether with
addition of propan-2-ol (3×70 ml), The extract was
dried over MgSO4, the solvent was removed under
reduced pressure, and the residue (7.5 g) was washed
with diethyl ether–hexane (1:6). The undissolved
material (~700 mg) contained (according to the NMR
data) 75% of compound VI and 25% of III. By col-
umn chromatography we isolated 50 mg of III.
b. A mixture of 3 g (34 mmol) of oxamide, 10.15 g
(68 mmol) of trifluoromethanesulfonamide, and 2.04 g
(68 mmol) of paraformaldehyde in 120 ml of
92% sulfuric acid was stirred for 40 at room tempera-
ture. The mixture was then poured into a mixture of ice
with sodium chloride, the precipitate (580 mg) was
filtered off and washed with diethyl ether–hexane
(1:6), and the undissolved material was recrystallized
from methanol. The aqueous filtrate was extracted with
ethyl acetate (4×80 ml), the extract was dried over
MgSO4, the solvent was removed under reduced pres-
sure, and the residue (9.5 g) was washed with diethyl
ether–hexane (1:6). The undissolved residue (2.5 g)
contained 80% of compound III and 20% of IV; it was
subjected to column chromatography (diethyl ether–
hexane, 3:1; diethyl ether–hexane–acetone, 2:3:1),
and compound III thus isolated was recrystallized
from methanol. Yield 2 g (24%).
90°C, cooled, poured into ice water, and extracted with
diethyl ether–propan-2-ol. The extract was dried over
MgSO4, the solvent was removed, and the residue,
compound V (3.16 g), was purified by column chroma-
tography using hexane–diethyl ether (6:1 to 1:3) as
eluent.
Reaction of oxamide with N,N′-methylenedi(tri-
fluoromethanesulfonamide) (VII) and paraformal-
dehyde. Paraformaldehyde, 0.1 g (3.2 mmol), was
added to a solution of 0.14 g (1.6 mmol) of oxamide in
5 ml of concentrated sulfuric acid, the mixture was
heated until it became homogeneous and cooled to
room temperature, and 0.5 g (1.6 mmol) of compound
VII was added under vigorous stirring. The mixture
was heated for 2–3 h at 60–90°C until compound VII
disappeared (TLC), cooled, poured into a mixture of
ice with sodium chloride, and extracted with diethyl
ether–propan-2-ol. The extract was dried over MgSO4
and evaporated to obtain ~0.5 g of a colorless crys-
talline substance which contained (according to the
NMR data), heterocyclic compound VI and a small
impurity of trifluoromethanesulfonamide.
N-[(Trifluoromethylsulfonyl)aminomethyl]ox-
1
amide (III). White crystals, mp 240–242°C. H NMR
spectrum (DMSO-d6), δ, ppm: 4.55 d (2H, NCH2N, J =
6.4 Hz), 7.86 s and 8.16 s (1H each, CONH2), 9.34 t
(1H, NHCO, J = 5.6 Hz), 10.13 br.s (1H, NHSO2).
13C NMR spectrum (DMSO-d6), δC, ppm: 48.08
(NCN), 119.32 q (CF3, J = 321.14 Hz), 160.65 s
(NH2C=O), 161.35 s (NHC=O). 19F NMR spectrum
(CD3CN): δF –77.89 ppm. Found, %: C 19.50; H 2.71;
F 23.31. C6H6F3N3O4S. Calculated, %: C 19.28;
H 2.43; F 22.87.
c. A mixture of 0.5 g (5.7 mmol) of oxamide, 2.12 g
(14.2 mmol) of trifluoromethanesulfonamide, and
0.43 g (14.2 mmol) of paraformaldehyde in 20 ml of
concentrated sulfuric acid was stirred for 4–5 h at 60°C
and for 1 h at 90–95°C. The mixture was cooled and
poured into a mixture of ice with sodium chloride, the
precipitate was filtered off, and the filtrate was
extracted first with diethyl ether–hexane (1:6) to
remove unreacted trifluoromethanesulfonamide and
compound VII and then with diethyl ether–propan-2-ol
to isolate compound VI (major product). The extracts
were dried over MgSO4, the solvent was removed, and
crude product VI (0.56 g) was purified by recrystal-
lization from propan-2-ol.
N,N′-Bis[(trifluoromethylsulfonyl)aminomethyl]-
oxamide (IV). White crystals, mp 215–217°C.
1H NMR spectrum (DMSO-d6), δ, ppm: 4.57 d (4H,
NCH2N, J = 6.23 Hz), 9.54 t (2H, NHCO, J =
6.35 Hz), 10.18 br.s (2H, NHSO2). 13C NMR spectrum
(DMSO-d6), δC, ppm: 48.05 (NCN), 119.42 q (CF3, J =
321.8 Hz), 159.63 s (C=O). 19F NMR spectrum
(CD3CN): δF –77.89 ppm. Found, %: C 18.00; H 2.56;
F 27.77; N 12.73. C6H8F6N4O6S2. Calculated, %:
C 17.57; H 1.97; F 27.78; N 13.66.
d. A mixture of 1 g (11.4 mmol) of oxamide and
5.08 g (34.1 mmol) of trifluoromethanesulfonamide in
50 ml of concentrated sulfuric acid was stirred at 60°C
until it became homogeneous. The mixture was cooled
to room temperature, and 1.02 g (34.1 mmol) of
paraformaldehyde was added in small portions (the
mixture thickened and was diluted with 20 ml of con-
centrated sulfuric acid). The mixture was then stirred
for 10 h at room temperature, for 30 min at 60°C (until
the precipitate dissolved completely), and for 2 h at
Bis[(trifluoromethylsulfonyl)aminomethyl]
ethanedioate (V). Colorless needles, mp 102–103°C.
IR spectrum (KBr), ν, cm–1: 3314, 3071, 2999, 2970,
1722, 1426, 1378, 1270, 1231, 1202, 1154, 1115, 923,
898, 679, 607, 507, 404. Raman spectrum, ν, cm–1:
3312, 2997, 2970, 1672, 1423, 1371, 1227, 1152,
1
909, 764, 566, 390, 335, 313. H NMR spectrum
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 10 2010

CONDENSATION OF TRIFLUOROMETHANESULFONAMIDE
1475
(DMSO-d6), δ, ppm: 3.90 s (4H, CH2), 10.0 br.s
(1H, NH), 12.9 br.s (1H, NH). 13C NMR spectrum
(DMSO-d6), δC, ppm: 44.03 (NCO), 119.41 q (CF3, J =
321.8 Hz), 169.72 s (CO). Found, %: C 18.05; H 1.49;
F 27.18; N 6.49; S 15.57. C5H5F3N2O5S. Calculated,
%: C 17.48; H 1.47; F 27.65; N 6.80; S 15.56.
This study was performed under financial support
by the Russian Foundation for Basic Research (project
no. 10-03-00110).
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