Reactions of trifluoromethanesulfonamide with amides and paraformaldehyde

Article abstract of DOI:10.1134/S1070428007060012

Two- and three-component condensations of paraformaldehyde with trifluoromethanesulfonamide, acetamide, trifluoroacetamide, 1H-benzotriazole, methanesulfonamide, and malonamide were studied. N-Hydroxymethyl derivatives of trifluoroacetamide and 1H-benzotriazole reacted with trifluoromethanesulfonamide to give N-(trifluoroacetylaminomethyl)- and N-(1H-benzotriazol-1-ylmethyl)- substituted derivatives of tri-fluoromethanesulfonamide, as well as N,N'-methylenebis(trifluoromethylsulfonamide) and N-(trifluoromethyl- sulfonylaminomethyl)trifluoroacetamide as transamination products. Three-component condensation of trifluoromethanesulfonamide with paraformaldehyde and methanesulfonamide led to the formation of 1-methylsulfonyl-3,5-bis(trifluoromethylsulfonyl)hexahydro-1,3,5-triazine, and the reaction of trifluoromethanesulfonamide with paraformaldehyde and malonamide gave 4,10-bis(trifluoromethylsulfonyl)-2,4,8,10-tetraazaspiro-[5.5]undecane-1, 7-dione whose structure was proved by X-ray analysis.

Full text of DOI:10.1134/S1070428007060012

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2007, Vol. 43, No. 6, pp. 793–800. © Pleiades Publishing, Ltd., 2007.
Original Russian Text © V.I. Meshcheryakov, Yu.S. Danilevich, M.Yu. Moskalik, N.Yu. Stetsyura, V.E. Zavodnik, V.K. Bel’skii, B.A. Shainyan, 2007,
published in Zhurnal Organicheskoi Khimii, 2007, Vol. 43, No. 6, pp. 799–805.
Reactions of Trifluoromethanesulfonamide with Amides
and Paraformaldehyde
a
a
a
a
b
V. I. Meshcheryakov , Yu. S. Danilevich , M. Yu. Moskalik , N. Yu. Stetsyura , V. E. Zavodnik ,
b
a
V. K. Bel’skii , and B. A. Shainyan
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
Karpov Research Physicochemical Institute, Moscow, Russia
Received May 24, 2006
Abstract—Two- and three-component condensations of paraformaldehyde with trifluoromethanesulfonamide,
acetamide, trifluoroacetamide, 1H-benzotriazole, methanesulfonamide, and malonamide were studied. N-Hy-
droxymethyl derivatives of trifluoroacetamide and 1H-benzotriazole reacted with trifluoromethanesulfonamide
to give N-(trifluoroacetylaminomethyl)- and N-(1H-benzotriazol-1-ylmethyl)-substituted derivatives of tri-
fluoromethanesulfonamide, as well as N,N′-methylenebis(trifluoromethylsulfonamide) and N-(trifluoromethyl-
sulfonylaminomethyl)trifluoroacetamide as transamination products. Three-component condensation of tri-
fluoromethanesulfonamide with paraformaldehyde and methanesulfonamide led to the formation of 1-methyl-
sulfonyl-3,5-bis(trifluoromethylsulfonyl)hexahydro-1,3,5-triazine, and the reaction of trifluoromethanesulfon-
amide with paraformaldehyde and malonamide gave 4,10-bis(trifluoromethylsulfonyl)-2,4,8,10-tetraazaspiro-
[
5.5]undecane-1,7-dione whose structure was proved by X-ray analysis.
DOI: 10.1134/S1070428007060012
Condensations of carboxamides RC(O)NH with
fluoromethanesulfonamide) (II) [6]. The three-com-
ponent condensation of trifluoromethanesulfonamide
with acetamide and paraformaldehyde gave a mixed
analog of II, N-(trifluoromethylsulfonylaminomethyl)-
acetamide (III) [6]. In continuation of these studies, in
the present work we examined some two- and three-
component condensations involving paraformalde-
hyde, amide I, and acetamide (IV), trifluoroacetamide
(V), 1H-benzotriazole (VI), methanesulfonamide
(VII), and malonamide (VIII).
2
formaldehyde and other aldehydes R′CHO were
shown [1–3] to give N-(α-hydroxyalkyl)amides
RC(O)NHCH(R′)OH and N,N′-alkylidenebisamides
[
RC(O)NH] CHR′. In the reversible reaction of acet-
2
amide with formaldehyde, N-(hydroxymethyl)acet-
amide CH CONHCH OH, N,N′-oxydimethylenedi-
3
2
acetamide (CH CONHCH ) O, and N,N′-methylenedi-
3
2 2
acetamide (CH CONH) CH were detected by NMR
3
2
2
spectroscopy [1, 4]. The formation of N,N′-alkylidene-
diamides is catalyzed by sulfuric [2] or trifluoro-
methanesulfonic acid [3]. N-Hydroxymethyl deriva-
tives of sulfonamides readily undergo disproportiona-
tion and polymerization [1]; however, alkane- and
arenesulfonamides smoothly react with formaldehyde
to give N-sulfonyl-substituted hexahydro-1,3,5-tri-
azines, dihydro-1,3,5-dioxazines, and tetrahydro-1,3,5-
oxadiazines [2, 5].
As shown in [6], the reaction of amide I with para-
formaldehyde is very sensitive to the temperature,
reaction time, and reactant ratio. Likewise, the results
of three-component condensation of amide I with para-
formaldehyde and acetamide (or acetonitrile) strongly
depended on the conditions. In 96% H SO (acet-
2
4
amide) or 85% H PO (acetonitrile) mixed condensa-
3
4
tion product III was obtained. When the reaction of I
with paraformaldehyde and acetamide was performed
in 92% sulfuric acid in the presence of P O (the
We previously studied the reaction of trifluoro-
methanesulfonamide (I) with paraformaldehyde and
found that, depending on the conditions, it leads to the
formation of a number of linear and cyclic products
2
5
amount of the latter corresponded to complete binding
of water present in 92% sulfuric acid; i.e., the reaction
occurred in a mixture of anhydrous sulfuric and phos-
[
6]. The major linear product is N,N′-methylenedi(tri-
793

7
94
MESHCHERYAKOV et al.
phoric acids), the major product was previously de-
scribed 1,3,5-tris(trifluoromethylsulfonyl)hexahydro-
produce cyclic compounds like IX or X, and the only
identified and isolated product was N,N′-methylenedi-
(trifluoroacetamide) (XI) (Scheme 3).
1
,3,5-triazine (IX) [6] rather than compound III
(
Scheme 1). No acetamide condensation products were
Scheme 3.
detected in the reaction mixture.
H SO
2
4
CF CONH
+
CH O
CF CONHCH NHCOCF
3 2 3
3
2
2
Scheme 1.
V
XI
CF SO NH
+
CH CONH2
+
CH O
2
3
2
2
3
I
IV
We failed to effect cyclization of compound XI by
reaction with paraformaldehyde in sulfuric acid; in-
stead, N-hydroxymethyltrifluoroacetamide (XII) was
obtained (Scheme 4). The yield of XII was poor (the
conversion was only ~50% in 3 h), but it can be readily
separated from unreacted initial bis-amide XI and pu-
rified by sublimation.
SO CF
2
3
N
H SO –H PO
4
2
4
3
N
N
CF SO
SO CF3
2
3
2
IX
Our attempt to effect cyclization of previously pre-
pared compound III via reaction with paraformalde-
hyde resulted in the formation of known symmetric
compound X instead of expected unsymmetrically sub-
stituted oxadiazine (Scheme 2). Obviously, the reaction
involves transamination with liberation of acetamide.
Scheme 4.
H SO
2 4
XI
+
CH O
CF CONHCH OH
3 2
2
XII
The synthesis of compound XII via hydroxymeth-
ylation of trifluoroacetamide was reported in [1, 9]; it
was also used as amidomethylating agent [9–13]; how-
ever, we found no published spectral parameters of this
compound. We examined the reaction of N-hydroxy-
methyltrifluoroacetamide (XII) with trifluoromethane-
sulfonamide (I) with a view to obtain N-(trifluoro-
methylsulfonylaminomethyl)trifluoroacetamide (XIII).
According to the NMR data, this reaction led to a mix-
ture of products (Scheme 5).
Scheme 2.
CF SO NHCH NHCOCH
3
2
2
3
III
O
CH O, H SO
2
2
4
–
MeCONH2
N
N
CF SO
SO CF3
3
2
2
X
O
Scheme 5.
III
N
N
H SO
4
CF SO
COCH3
2
3
2
CF CONHCH OH
+
CF CONH
I
+
II
3
2
3
2
XII
I
50%
15%
Hydroxymethylation of amides is very sensitive to
the hydroxymethylating agent [1]. N,N′-Methylene-
diacetamide (CH CONH) CH cannot be obtained by
+
IX
+
XI
+
CF SO NHCH NHCOCF
3
2
2
3
3
2
2
4
%
8%
XIII, 23%
reaction of acetamide with trioxane, chlorodimethyl
ether, or bis(chloromethyl) ether; it is formed only
Unreacted sulfonamide I and a part of bis-sul-
fonamide II were removed by washing the product
mixture with water. In keeping with the relative signal
intensities in the H ad F NMR spectra, the residue
contained ~60% of target product XIII, ~30% of XI,
when urotropin is used as source of CH O [7]. Amido-
2
methylation of arenes with urotropin in trifluoroacetic
acid is accompanied by side formation of acid decom-
position products such as trifluoroacetamide (V) and
N,N′-methylenedi(trifluoroacetamide) [8].
1
19
~
5% of IX, and ~5% of II. Compounds I, II, IX, and
With a view to compare the behavior of sulfon-
amides and carboxamides in the hydroxymethylation
processes, trifluoroacetamide (V) was brought into
reaction with paraformaldehyde at a ratio of 2:1 in
concentrated sulfuric acid. Unlike compound I [6],
trifluoroacetamide with paraformaldehyde did not
XI were identified in the product mixture by com-
1
13
19
paring the H, C, and F NMR signals with those of
authentic samples obtained in [6] and in the present
work. N-(Trifluoromethylsulfonylaminomethyl)tri-
fluoroacetamide (XIII) was identified on the basis of
1
13
almost complete coincidence of the H and C signals
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 6 2007

REACTIONS OF TRIFLUOROMETHANESULFONAMIDE WITH AMIDES
795
from the methylene group with the corresponding
signals of its closest analog, N-(trifluoromethylsul-
fonylaminomethyl)acetamide (III) [6]. The chemical
shifts of the methylene carbon atoms in compounds II,
major product was N-(1H-benzotriazol-1-ylmethyl)tri-
fluoromethanesulfonamide (XV). Hexahydrotriazine
IX is readily separated from compound XV by recrys-
tallization from methanol, where the latter is readily
soluble. Like other N-substituted trifluoromethanesul-
fonamides, N-(1H-benzotriazol-1-ylmethyl)trifluoro-
methanesulfonamide (XV) is a strong NH acid. Its pKa
value in methanol is equal to 11.08, i.e., it is almost
similar to that of trifluoromethanesulfonamide itself
IX, XI, XIII, and III are quite characteristic (δ 53.22,
C
6
1.9, 45.3, 49.3, and 49.4 ppm, respectively [6]);
therefore, the assignment based thereon seems to be
reliable.
It is known that three-component reaction of
(
pK 11.06 [15]).
a
1
H-benzotriazole with sulfonamides and aldehydes
leads to 1-(organylsulfonylaminoalkylidene)benzotri-
azoles [14]. For example, 1-(methylsulfonylamino-
methyl)-1H-benzotriazole was obtained by reaction of
methanesulfonamide with formaldehyde and 1H-ben-
zotriazole or by condensation of methanesulfonamide
with 1-hydroxymethyl-1H-benzotriazole [14]. We have
found that 1-hydroxymethyl-1H-benzotriazole (XIV)
reacts with trifluoromethanesulfonamide in a similar
way to give mixed condensation product (XV).
The formation of compound II in addition to XIII
and XV in the reactions shown in Schemes 5 and 6, as
well as of compounds IX and XI in the first of these,
seems to be surprising, for the reaction mixtures con-
tained no free formaldehyde. Obviously, both reactions
include partial transamination of initially formed com-
pounds XIII and XV, as shown in Scheme 7. Unlike
the reaction with N-hydroxymethyltrifluoroacetamide
(Scheme 5), no symmetric product like (RR′N) CH
2 2
1
According to the H NMR data, more than 30% of
(analogous to XI) was formed in the reaction with
1-hydroxymethyl-1H-benzotriazole. The reason is that
N,N′-methylenebis(trifluoromethanesulfonamide) (II)
is also formed (Scheme 6).
1
H-benzotriazole liberated during the process
(
Scheme 7) gives a salt with concentrated sulfuric acid
Scheme 6.
and is thus excluded from further reacting.
N
N
N
Mixed cyclic condensation product, 1-methylsul-
fonyl-3,5-bis(trifluoromethylsulfonyl)hexahydro-1,3,5-
triazine (XVI, a close analog of IX), was formed
together with linear product II in the reaction of
an equimolar mixture of trifluoromethanesulfonamide
AcOH
N
+
CH O
N
2
N
H
CH OH
2
VI
CF SO NH , H SO
XIV
(
I) and methanesulfonamide (VII) with paraformalde-
N
N
3
2
2
2
4
hyde in concentrated sulfuric acid (Scheme 8). The
ratio of compounds II and XVI before separation was
N
+
II
~5:1. Compound II was washed off from the product
CH NHSO CF
3
2
2
mixture with diethyl ether–hexane (2:1), and column
chromatography of the residue gave individual com-
pound XVI.
XV
The formation of compound II can be avoided by
carrying out one-pot three-component condensation of
The structure of XVI is confirmed by the presence
1
3
1
H-benzotriazole with paraformaldehyde and trifluoro-
in its C NMR spectrum of a signal at δ 41 ppm from
C
methanesulfonamide (I) on slight heating; in this case,
a small amount of compound IX was formed, and the
the CH SO group, a quartet at δ 120 ppm from the
3
2
C
CF carbon atom, and two closely located methylene
3
Scheme 7.
R'
H+
R'
CH2 CF SO NH
R'
SO CF
H+
R'
SO CF
2 3
3
2
2
2
3
N
R
OH
N
R
N
R
N
H
N
R
N
–
H O
2
H
H
XIII, XV
CF SO NHCH
CF SO NH
3
2
2
R'
CH2
CF CONH
CF SO
CH2
3
2
2
3
2
3
2
N
II
IX
N
R
XI
–H+
–H+
–
RR'NH
H
–
CF SO NH
3 2 2
R = CF CO, R' = H
3
R = CF CO
3
RR' = o-C H –N=N–
6
4
R' = H
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 6 2007

7
96
MESHCHERYAKOV et al.
Scheme 8.
at a frequency typical of linear amides. On the basis of
the above data, the product was assumed to have
a cyclic structure containing C(O)NH and CF SO N
CF SO NH
+
CH SO NH
3 2 2
3
2
2
I
VII
3
2
fragments. Its structure was finally proved by X-ray
analysis as 4,10-bis(trifluoromethylsulfonyl)-2,4,8,10-
tetraazaspiro[5.5]undecane-1,7-dione (XVII); obvious-
ly, it was formed via three-component condensation
involving not only both amide groups of initial malon-
amide but also its activated methylene group as shown
in Scheme 9.
CH O, H SO
4
2
2
(
CF SO NH) CH
3 2 2 2
II
SO CF
2
3
N
+
N
N
CF SO
SO CH
2 3
3
2
Scheme 9.
XVI
H
CH
O
2
O
carbon signals at δ 61.2 and 61.9 ppm with an in-
tensity ratio of 2:1. The H NMR spectrum recorded at
C
H
N
CH2
1
H
N
SO CF3
2
O
H
H
H
H
H
room temperature contained two signals: a singlet from
the methylsulfonyl group at δ 3.1 ppm and a very
broad singlet at δ 5.3 ppm from the methylene protons,
their intensity ratio being 1:2. Temperature variation
leads to splitting of the latter signal into separate
signals from axial and equatorial protons in the six-
membered ring; thise data indicate that heteroring XVI
O
H
CF SO
N
O
3
2
CH2
O
N
O
H
CH2
CF SO
3
2
NH
N
N
H+
4H O
(
like compound IX) is conformationally labile [16].
HN
–
2
O
Unexpectedly, in the three-component condensation
SO CF3
2
of malonamide (VIII) with trifluoromethanesulfon-
amide (I) and paraformaldehyde we isolated a high-
melting substance which showed in the H NMR spec-
XVII
1
According to the X-ray diffraction data (Fig. 1;
Tables 1, 2), the interatomic distances and bond angles
in molecule XVII correspond to standard values. Both
spiro-fused heterorings adopt almost similar unsym-
metrical chair conformations. The C , C , C , and N
atoms in the C C C N N ring lie in one plane within
.08 Å, while the N and C atoms deviate from that
plane in opposite directions by 0.66 and 0.12 Å,
respectively. In the second ring, the C , C , C , and N
atoms lie in one plane within 0.09 Å, and the N and
trum a singlet at δ 8.8 ppm from NH proton and two
1
3
AB quartets at δ 4.0 and 4.8 ppm. The C NMR spec-
trum contained two signals at δ 50–56 ppm from
C
1
2
3
2
methylene carbon atoms, a quartet signal from CF3
1
2
3
1
2
group, and a signal at δ 165 from amide carbonyl
C
1
4
carbon atom. In the IR spectrum of this compound we
0
–
1
observed a carbonyl absorption band at 1680 cm , i.e.,
1
6
7
3
1
F
4
3
3
O
F
5
C deviate from that plane by 0.26 and 0.66 Å,
6
O
8
respectively (in opposite directions). Molecules XVII
in crystal are linked through intermolecular hydrogen
bonds NH···O involving both NH groups and carbonyl
oxygen atoms; as a result, chains along the [010] axis
are formed (Fig. 2, Table 2).
C
4
1
N
S
4
6
7
F
C
C
2
4
O
O
3
N
1
N
2
F
2
5
2
S
O
C
9
1
3
C
C
C
6
4
F
C
5
EXPERIMENTAL
5
C
F
2
N
The NMR spectra were recorded on a Bruker DPX-
1
O
1
4
00 spectrometer at 400, 100, and 376 MHz for H,
1
3
19
C, and F, respectively; the chemical shifts were
Fig. 1. Structure of the molecule of 4,10-bis(trifluoromethyl-
sulfonyl)-2,4,8,10-tetraazaspiro[5.5]undecane-1,7-dione
XVII) according to the X-ray diffraction data.
measured relative to hexamethyldisiloxane (internal
1
13
19
(
reference; H, C) or CCl F ( F). The progress of
3
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 6 2007

REACTIONS OF TRIFLUOROMETHANESULFONAMIDE WITH AMIDES
797
Table 1. Bond lengths d and bond angles φ in the molecule of 4,10-bis(trifluoromethylsulfonyl)-2,4,8,10-tetraazaspiro[5.5]-
undecane-1,7-dione (XVII)
Bond
d, Å
Bond
d, Å
Bond
d, Å
Bond
d, Å
1
4
1
4
2
9
3
5
S –O
1.413(2)
1.420(2)
1.593(2)
1.834(3)
1.405(3)
1.416(3)
1.600(2)
O –C
1.224(3)
1.228(3)
1.461(4)
1.464(4)
1.318(4)
1.437(4)
1.446(4)
S –C
1.830(5)
1.315(4)
1.308(4)
1.292(4)
1.284(6)
1.308(7)
1.276(6)
N –C
1.476(3)
1.339(4)
1.445(4)
1.524(4)
1.526(3)
1.528(4)
1.547(4)
1
3
1
2
7
2
3
4
3
6
1
8
8
8
9
9
9
4
7
S –O
O –C
F –C
N –C
1
1
2
4
6
S –N
N –C
F –C
N –C
1
8
1
3
1
5
7
4
2
S –C
N –C
F –C
C –C
2
6
2
4
1
S –O
N –C
F –C
C –C
2
5
3
2
5
1
S –O
N –C
F –C
C –C
2
3
6
1
S –N
N –C
F –C
C –C
Angle
φ, deg
Angle
φ, deg
Angle
φ, deg
Angle
φ, deg
4
1
3
1
1
7
1
2
2
1
2
1
3
3
8
2
1
1
1
1
1
4
5
5
2
2
2
O S O
121.79(15)
112.74(13)
108.57(13)
103.94(16)
105.39(15)
102.17(15)
123.06(18)
108.69(15)
109.27(14)
105.1(2)00
104.4(2)00
104.7(2)00
C C C
107.5(2)
111.8(2)
109.7(2)
110.2(2)
123.5(3)
118.1(3)
118.4(2)
107.8(2)
108.5(2)
122.8(2)
119.8(2)
117.2(2)
C N C
112.9(2)00
123.81(18)
121.1(2)00
128.2(2)00
113.1(2)00
122.39(19)
121.36(18)
125.8(2)00
112.2(2)00
108.4(2)00
106.17(19)
110.7(2)00
F C F
108.9(3)
109.5(3)
107.7(3)
111.4(2)
109.9(2)
109.4(3)
110.0(5)
106.8(5)
109.4(6)
110.9(5)
110.7(4)
109.0(3)
4
1
4
1
2
1
1
1
3
3
8
O S N
C C C
C N S
F C F
3
1
1
2
3
1
2
8
O S N
N C C
C N S
F C F
4
1
8
8
8
5
2
3
1
2
4
2
3
8
O S C
N C N
C N C
F C S
3
1
1
4
6
3
5
2
8
O S C
O C N
C N C
F C S
1
1
1
4
1
1
1
3
6
3
2
2
6
1
8
N S C
O C C
C N S
F C S
6
2
2
4
5
3
6
9
O S O
N C C
C N S
F C F
6
2
3
3
3
5
7
4
6
9
O S N
N C C
C N C
F C F
5
2
4
6
5
1
7
4
4
2
4
9
O S N
N C N
C C C
F C F
6
2
9
9
9
2
7
4
5
1
6
9
O S C
O C N
C C C
F C S
5
2
2
7
1
7
1
4
9
O S C
O C C
C C C
F C S
3
2
4
7
1
5
1
5
9
N S C
N C C
C C C
F C S
Table 2. Hydrogen bonds in the crystal structure of 4,10-bis(trifluoromethylsulfonyl)-2,4,8,10-tetraazaspiro[5.5]undecane-
1
,7-dione (XVII)
D–H···A
d(D–H), Å
d(H···A), Å
d(D···A), Å
∠ DHA, deg
Symmetry operation
2
2
1
2
N –H(N ) ···O
0.87
0.86
1.95
2.26
2.802(3)
2.964(3)
166.6
139.7
1 – x, 1 – y, –z
1 – x, –y, –z
4
4
N –H(N ) ···O
reactions was monitored by TLC on silica gel 60 F-254
plates (hexane–diethyl ether, 1:2).
11.572(2), c = 11.626(2) Å; β = 103.12(3)°; V =
1669.6(6) Å ; Z = 4; ρ = 1.784 g/cm . Final divergence
3
3
factors: R = 0.045, R = 0.115 [from 3271 reflections
with I > 2σ(I)].
w
X-Ray analysis of a 0.24×0.14×0.10-mm single
crystal of compound XVII was performed on an
Enraf–Nonius CAD4 diffractometer (MoK irradiation,
N,N′-Methylenebis(trifluoroacetamide) (XI). Tri-
fluoroacetamide, 1.5 g, was dissolved in 15 ml of
concentrated sulfuric acid, and 0.2 g of paraformalde-
hyde was added in small portions under stirring. The
mixture was stirred for 3 h at room temperature,
poured onto ice, and extracted with diethyl ether. The
α
β-filter, θ/2θ scanning). No correction for absorption
was introduced. The set of experimental reflections
was treated with account taken of the Lorentz factor
and polarization. The structure was solved by the
direct method and was refined by the full-matrix least-
squares procedure in anisotropic approximation for
non-hydrogen atoms and isotropic approximation for
hydrogen atoms. C H F N O S ; colorless prisms
extract was dried over MgSO , the solvent was dis-
4
tilled off, and the residue was dried under reduced
pressure and purified by recrystallization from ethanol.
9
10
6
4
6 2
(
from methanol); monoclinic crystal system, space
Yield 1.05 g (68%), mp 196–198°C (sublimes above
1
group P2 /c; unit cell parameters: a = 12.743(3), b =
180°C [8]). H NMR spectrum (CD
3
CN), δ, ppm:
1
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 6 2007

7
98
MESHCHERYAKOV et al.
J
= 286.1 Hz), 158.26 q (CO, JCF = 36.8 Hz).
CF
1
9
F NMR spectrum (CD CN): δ –77.14 ppm. Found,
3
F
%
: C 25.89; H 2.82; N 10.24. C H F NO . Calculated,
3 4 3 2
%: C 25.19; H 2.82; N 9.79.
Reaction of 2,2,2-trifluoro-N-(hydroxymethyl)-
acetamide with trifluoromethanesulfonamide. Tri-
fluoromethanesulfonamide, 0.42 g (2.8 mmol), was
dissolved in 15 ml of concentrated sulfuric acid on
heating to 32°C, 0.4 g (2.8 mmol) of compound XII
was added in small portions under vigorous stirring,
and the mixture was stirred for 1 h at room temperature
and left overnight. It was then stirred for 1.5 h at 40°C
and for 1 h at 60–65°C, cooled, poured into an ice–salt
mixture, and extracted with diethyl ether (3×30 ml).
The extract was dried over magnesium sulfate, the sol-
vent was removed, and the solid residue (0.55 g) was
dried under reduced pressure. After removal of initial
trifluoromethanesulfonamide by washing with water,
the residue (0.15 g) contained (according to the NMR
data) ~5% of II, ~10% of IX, ~25% of XI, and ~60%
of XIII.
4
4
1
H
N
O
2
′
2
′
N
2
″
H
O
2
2
H
N
1
′
O
4
″
4″
N
H
Fig. 2. Intermolecular hydrogen bonds in the crystal struc-
ture of 4,10-bis(trifluoromethylsulfonyl)-2,4,8,10-tetraaza-
spiro[5.5]undecane-1,7-dione (XVII).
13
4
.77 m (2H, CH ), 8.15 br.s (2H, NH). C NMR spec-
2
2
,2,2-Trifluoro-N-(trifluoromethylsulfonyl-
1
trum (CD CN), δ , ppm: 45.31 (CH ), 115.74 q (CF ,
3
C
2
3
aminomethyl)acetamide (XIII). H NMR spectrum
(CD CN), δ, ppm: 4.71 t (2H, CH , J = 6.2 Hz), 7.67 s
J
= 287.8 Hz), 158.20 q (CO, JCF = 37.7 Hz).
F NMR spectrum (CD CN): δ –76.77 ppm. Found,
: C 25.24; H 1.72; N 11.90. C H F N O . Calculated,
CF
19
3
2
3
F
1
3
(
(
1H, NHSO ), 8.40 s (1H, NHCO). C NMR spectrum
CD CN), δ , ppm: 49.26 (CH ), 116.73 q (CF CO,
2
%
%
5 4 6 2 2
3
C
2
3
: C 25.22; H 1.69; N 11.77.
,2,2-Trifluoro-N-(hydroxymethyl)acetamide
XII). Paraformaldehyde, 0.73 g (0.024 mol), was
dissolved in 10 ml of concentrated sulfuric acid, 1 g
4.2 mmol) of N,N′-methylenebis(trifluoroacetamide)
was added in small portions under vigorous stirring,
and the mixture was stirred for 3 h at room temperature
and poured into an ice–salt mixture. The precipitate of
initial N,N′-methylenebis(trifluoroacetamide), 0.25 g,
was filtered off, and the filtrate was extracted with
three portions of diethyl ether, neutralized with
NaHCO , and extracted with three portions of ethyl
acetate. The organic extracts were dried over MgSO4
and evaporated to isolate 0.3 g of N,N′-methylenebis-
trifluoroacetamide) from the ether extract and 0.25 g
of amide XII from ethyl acetate. The latter was purifi-
ed by vacuum sublimation. Yield 50% (on the reacted
initial compound), mp 102–104°C; published data [2]:
mp 105°C. H NMR spectrum (CD CN), δ, ppm: 4.05 t
JCF = 287.0 Hz), 120.47 q (CF SO , J = 319.9 Hz),
3
2
19
CF
2
1
58.37 q (CO, JCF = 37.8 Hz). F NMR spectrum
(
(
CD CN): δ , ppm: –79.36 s (CF SO ), –76.99 s
3
F
3
2
(
CF CO).
3
(
N-(1H-1,2,3-Benzotriazol-1-ylmethyl)trifluoro-
methanesulfonamide (XV). a. A suspension of 2.5 g
of trifluoromethanesulfonamide and 2 g of 1-hydroxy-
methyl-1H-benzotriazole (XIV) (prepared by the
procedure described in [17]) in 20 ml of concentrated
sulfuric acid was stirred until it became thick, an addi-
tional 10 ml of concentrated sulfuric acid was added,
and the mixture was stirred for 2 h. The mixture was
then poured into a saturated solution of NaCl contain-
ing ice and extracted with diethyl ether (3×30 ml), the
extract was dried over magnesium sulfate, and the
solvent was distilled off under reduced pressure. The
residue was washed with hexane–diethyl ether to
remove N,N′-methylenebis(trifluoromethanesulfon-
amide) and recrystallized from ethanol.
3
(
1
3
(
1H, OH), 4.72 t (2H, CH ), 8.15 br.s (1H, NH). In the
2
spectra recorded at 60°C, the OH and NH signals were
located in a stronger field, at δ 3.86 and 7.99 ppm,
b. Paraformaldehyde, 1.3 g, was added in small
portions under stirring to a suspension of 5 g of benzo-
triazole and 6.3 g of trifluoromethanesulfonamide in
50 ml of concentrated sulfuric acid, the mixture was
stirred for 3 h at 70°C, cooled, and poured onto ice,
respectively, while the position of the CH signal
2
1
3
almost did not change (δ 4.76 ppm). C NMR spec-
trum (CD CN), δ , ppm: 64.42 (CH ), 117.10 q (CF ,
3
C
2
3
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 6 2007

REACTIONS OF TRIFLUOROMETHANESULFONAMIDE WITH AMIDES
799
and the precipitate was filtered off and recrystallized
from ethanol. Yield 10.5 g (90%), mp 164–166°C.
acid, 8.76 g of trifluoromethanesulfonamide was
added, and the mixture was heated to about ~60°C
until it became homogeneous. The solution was cooled
to 45°C, 2.36 g of paraformaldehyde was added in
small portions under vigorous stirring, and the mixture
was heated to 80–90°C, stirred for 5 h at that tempera-
ture, and poured into ice water. The precipitate, 4.8 g,
was filtered off, dried in air, and treated with diethyl
ether–hexane (1:2). From the organic solution we
isolated 2.52 g of N,N′-methylenebis(trifluoromethane-
sulfonamide) (II) which was identical to an authentic
sample [6]. The undissolved material was 4,10-bis(tri-
fluoromethylsulfonyl)-2,4,8,10-tetraazaspiro[5.5]un-
1
H NMR spectrum (CD CN), δ, ppm: 6.10 d (2H, CH ,
3
2
J = 6.2 Hz), 7.48 d.d.d (1H, 7-H, J = 8.2, 7.2, 0.8 Hz),
.64 d.d.d (1H, 8-H, J = 8.0, 7.4, 0.7 Hz), 7.83 d
1H, 9-H, J = 8.5 Hz), 8.07 d (1H, 6-H, J = 8.3 Hz),
7
(
8
1
3
.22 br.s (1H, NH). C NMR spectrum (CD CN), δ ,
3 C
6
ppm: 55.73 (CH ), 111.11 (C ), 120.30 q (CF , J =
3
1
2
3
CF
7
9
8
19.9 Hz), 120.46 (C ), 125.59 (C ), 129.20 (C ),
33.18 (C ), 147.34 (C ). F NMR spectrum (CD CN):
5
4
19
3
δF –79.35 ppm. Found, %: C 33.71; H 2.34; F 20.94;
N 19.04; S 12.03. C H F N O S. Calculated, %:
8
7
3
4
2
C 34.29; H 2.52; F 20.34; N 19.99; S 11.44. The
concentration of nitrogen is slightly lower than the
theoretical value due to the presence of a small impur-
ity of trifluoromethanesulfonamide (~5%, according to
decane-1,7-dione (XVII). Yield 2.27 g, mp 240–
1
242°C. H NMR spectrum (DMSO-d ), δ, ppm: 3.95 d
6
(1H, H in COCH CO), 4.14 d (1H, H in COCH CO,
A
2
B
2
1
the H NMR data) which we failed to separate.
JAB = 13.3 Hz), 4.76 d (1H, H in NCH N), 4.85 d
A′ 2
(
1H, H in NCH N, J = 11.0 Hz), 8.79 s (1H, NH);
B′ 2 AB
Reaction of trifluoromethanesulfonamide with
methanesulfonamide and paraformaldehyde. Tri-
fluoromethanesulfonamide, 3 g (0.02 mol), and
methanesulfonamide, 1.9 g (0.02 mol), were added
under stirring to 40 ml of concentrated sulfuric acid,
the mixture was heated to 40°C, 0.6 g (0.02 mol) of
paraformaldehyde was added over a period of 3 h, and
the mixture was stirred for 3 h. The mixture thickened
and was poured onto ice, and the precipitate was fil-
tered off, washed with a saturated solution of NaCl and
water, and dried under reduced pressure. The filtrate
was saturated with sodium chloride and extracted with
the H proton showed a weak coupling (J = 1.0 Hz)
with the NH proton. C NMR spectrum (DMSO-d ),
δC, ppm: 49.35 br.s (Cspiro), 56.11 (NCN), 119.28 q
(
trum (CD CN): δ –76.41 ppm. Found, %: C 24.00;
H 2.28; F 25.02; N 12.22; S 14.94. C H F N O S .
Calculated, %: C 24.11; H 2.25; F 25.43; N 12.50;
S 14.30.
A′
1
3
6
1
9
CF , J = 322.3 Hz), 165.58 (CO). F NMR spec-
3 CF
3
F
9
10
6
4
6 2
This study was performed under financial support
by the Russian Foundation for Basic Research (project
no. 07-03-00425).
diethyl ether, the extract was dried over MgSO and
4
evaporated, and the residue was dried under reduced
pressure. The residue was combined with the above
precipitate and treated with diethyl ether–hexane (2:1)
to remove compound II. The residue was subjected to
column chromatography on silica gel using solvent
mixtures with increasing polarity (hexane–diethyl
ether–acetone, 2:1:1; hexane–diethyl ether–acetone,
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:2:1; acetone; methanol) to isolate 0.5 g of 1-methyl-
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1
1
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(
(
4
(
CD CN), δ, ppm: 3.14 s (3H, CH ), 5.30 very broad s
3
3
1
3
6H, CH ). C NMR spectrum (CD CN), δ , ppm:
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2
6
4
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1
9
CF , J = 320.3 Hz). F NMR spectrum (CD CN):
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7
8
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N 9.79; S 22.54. C H F N O S . Calculated, %:
6
9
6
3
6 3
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1
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 6 2007