Oxymethylation of trifluoromethanesulfonamide with paraformaldehyde in ethyl acetate

Article abstract of DOI:10.1134/s1070428008020206

Acid-catalyzed reaction of trifluoromethanesulfonamide with paraformaldehyde in ethyl acetate led to the formation of oxymethylated products that did not form in the reaction carried out in sulfuric acid. Following products were obtained: 5-trifluoromethylsulfonyl-1,3-dioxazinane, 3,7-bis-(trifluoromethylsulfonyl)-1,5,3,7-dioxadiazocane, and a complex of trifluoromethanesulfonamide with 2,4,8,10-tetraoxospiro[5,5]undecene, 1:1. The spiroring resulted from the cyclization of pentaerythritol under the action of formaldehyde. The pentaerythritol formed in its turn by oxymethylation of the methyl group of ethyl acetate with paraformaldehyde followed by the reduction of the COOEt group into CH₂ OH by the formaldehyde.

Full text of DOI:10.1134/s1070428008020206

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2008, Vol. 44, No. 2, pp. 311−316. © ©Pleiades Publishing, Ltd., 2008.
Original Russian Text © V.I. Meshcheryakov, M.Yu. Moskalik, A. Kelling, U. Schilde, I.A. Ushakov, B.A. Shainyan, 2008, published in Zhurnal
Organicheskoi Khimii, 2008, Vol. 44, No. 2, pp. 313−317.
Oxymethylation of Trifluoromethanesulfonamide
with Paraformaldehyde in Ethyl Acetate
a
a
b
b
V. I. Meshcheryakov , M. Yu. Moskalik , A. Kelling , U. Schilde ,
a
a
I. A. Ushakov , and B. A. Shainyan
aFaworsky Irkutsk Institute of Chemistry, Siberian Division, Russian Academy of Sciences, Irkutsk, 664033 Russia
e-mail: bagrat@irioch.irk.ru
.
.
b
Chemisches Institut der Universitat Potsdam, Germany
Received May 21, 2007; final version November14, 2007
Abstract—Acid-catalyzed reaction of trifluoromethanesulfonamide with paraformaldehyde in ethyl acetate led
to the formation of oxymethylated products that did not form in the reaction carried out in sulfuric acid. Following
products were obtained: 5-trifluoromethylsulfonyl-1,3-dioxazinane, 3,7-bis-(trifluoromethylsulfonyl)-1,5,3,7-
dioxadiazocane, and a complex of trifluoromethanesulfonamide with 2,4,8,10-tetraoxospiro[5,5]undecene, 1:1.
The spiroring resulted from the cyclization of pentaerythritol under the action of formaldehyde. The pentaerythritol
formed in its turn by oxymethylation of the methyl group of ethyl acetate with paraformaldehyde followed by the
reduction of the COOEt group into CH OH by the formaldehyde.
2
DOI: 10.1134/S1070428008020206
We showed formerly that the reaction of trifluoro-
according to NMR data cyclic compounds VI–VIII
1
methanesulfonamide CF SO NH (I) with paraform-
whose structure was established from the analysis of H,
3
2
2
13
19
aldehyde in sulfuric acid led to the formation of linear
C, and F NMR spectra registered from the fractions
and cyclic condensation products II–V [1].
enriched with the corresponding components by means
of column chromatography [1].
CF SO NHCH NHSO CF
3
3
2
2
2
II
CF SO N(CH NHSO CF )
3 2
O
O
O
N
O
N
3
2
2
2
N
III
SO CF
CF SO
2
SO CF3
O
2
3
3
2
VI
VII
N
N
O
O
CF SO
SO CF
2 3
3
2
IV
N
N
SO CF
3
CF SO
2
3
2
CF SO
SO CF
3
N
3
2
2
N
N
SO CF
2
3
N
VIII
SO CF
2
3
Compound VI was assigned the dioxazinane structure
V
1
13
based on the presence in its H and C spectra of signals
indicating NCH O (3.7 and 71 ppm) and OCH O (4.7
2
2
In reaction of compound II with paraformaldehyde
and 95 ppm) groups in the ratio 2:1 [1]. However in the
in a mixture ethyl acetate–sulfuric acid at heating formed
spectra of six-membered rings IV and V these groups
3
11

312
MESHCHERYAKOV et al.
appeared close to each other and in a far weaker field,
IX formed through cyclization of pentaerythritol under
the action of formaldehyde. The pentaerythritol, in its
turn, formed (analogously to its industrial production by
reaction of formaldehyde with acetaldehyde) by triple
aldol condensation of formaldehyde with the activated
methyl group of ethyl acetate followed by reduction of
the ester group in the intermediate ethyl 3-hydroxy-2,2-
bis(hydroxymethyl)propionate and oxidation of the
formaldehyde.
~
5.3 ppm [1], and this fact induced us to investigate the
structure of the previously obtained compound in more
detail.
To this end we studied the reaction of amide I with
paraformaldehyde in ethyl acetate in the presence of
sulfuric acid. It turned out that under mild conditions
(
20°C, 6 h) just 5-trifluoromethylsulfonyl-1,3-dioxazi-
nane (VI) was the main product. This is indicated by the
1
appearance in the H NMR spectrum of two singlets at
We put to test this assumption by performing a
reaction of paraformaldehyde with excess ethyl acetate
at gradual addition of concn. H SO ; the reaction mixture
1
3
5
.3 and 5.2 ppm in a ratio 2:1, and in the C NMR
spectrum, of the corresponding signals at 79 and 95 ppm;
the obtained values of the chemical shifts were close to
2
4
was maintained for 24 h at room temperature and then
heated for 7 h at 80°C. Intermittently a sampling of the
reaction mixture was done, the sample was poured into
water, extracted with ethyl acetate, the extract was dried,
the solvent was removed, and the residue was analyzed
1
the analogous figures for heterocycle IV. The H NMR
*
spectrum of dioxazinane VI is temperature-dependent
in the fashion characteristic of the six-membered
heterocycles similarly to that we have previously
observed for its close analogs IV [2] and V [3].
1
by NMR. The main signals in the H NMR spectrum
5
-Trifluoromethylsulfonyl-1,3-dioxazinane (VI) for
were the peaks of 2,4,8,10-tetraoxospiro[5,5]undecane:
singlets at 3.7 and 4.7 ppm in the ratio ~2:1, and in the
spectral measurements was isolated by vacuum
1
13
19
distillation. According to H, C, and F NMR data it
contained an impurity of trifluoromethanesulfonamide,
and also of a compound of unestablished structure
containing an ethyl and a trifluoromethanesulfonyl
groups and a fragment OCN (δ 78.8 ppm).
13
C NMR spectrum, the resonances at ~71 and 95 ppm
in the ratio 2:1, and also a signal of a quaternary carbon
at 34.4 ppm. As far as we know this is the first example
of ester group COOR reduction into alcohol CH OH
2
group effected by formaldehyde.
Under more severe conditions (80°C, 3 h) the tri-
fluoromethanesulfonamide formed a complex with
CH OH
2
2,4,8,10-tetra-oxospiro[5,5]undecene, 1:1 (IX). Complex
CH3 COOEt + 3 CH O
HOCH2 C COOEt
2
IX was isolated by column chromatography on silica gel.
CH OH
2
Its structure was confirmed by the presence in the
1
H NMR spectrum of signals from NH , CCH O, and
2
2
13
CH OH
OCH O in a ratio 2:4:8, and in the C NMR spectrum,
2
2
2CH O, 2H O
2
2
of signals corresponding to CF , CCO, OCO, and
HOCH2 C CH2OH
3
_2
_
HCOOH, EtOH
quaternary carbon atom; the final proof of the structure
was obtained by X-ray diffraction analysis (see the table).
CH OH
2
1
Just the presence in the H NMR spectrum of complex
O
2
_2
CH O
O
2
IX of signals at 3.7 and 4.7 ppm in a ratio 2:1, and in the
C NMR spectrum the corresponding signals at ~71 and
5 ppm and also of a quartet from CF group, all the sig-
nals virtually coinciding with those in the C NMR spec-
trum of dioxazinane VI, was the reason of the erroneous
conclusion on formation of compound VI in [1].
H O
2
1
3
O
O
9
3
13
A complex was described in the literature of tri-
fluoromethanesulfonamide with a heterocyclic base,
tetrahydro-N-(4H-1,2,4-triazol-4-yl)-2H-pyran-2-imine,
also 1:1, with H-bonds betweent the protons of trifluoro-
methanesulfonamide and atoms N and N of the triazole
ring of the heterocycle of the length 1.84–2.13 Å [4].
With the less basic analog of this heterocycle, tetrahydro-
The formation of a spirocyclic complex IX was
unexpected for neither of the reagents contained
a quaternary carbon atom. We suggested that complex
1
2
*
The comprehensive description of the results of experimental and
theoretical conformation study of compound VI by means of
2
H-pyran-2-one N-methyl-N-phenylhydrazone trifluoro-
dynamic NMR and quantum chemistry will be published elsewhere.
methanesulfonamide did not form an adduct [4].
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 2 2008

OXYMETHYLATION OF TRIFLUOROMETHANESULFONAMIDE
Bond lengths (l), bond (ϕ) and torsion (θ) angles in complex IX
313
Bond
l, Å
Bond
l, Å
1
1
2
3
2
3b
S –N
1.561(5)
1.766(7)
1.413(3)
1.393(9)
1.302(5)
1.01(4)
C –C (C –C )
1.525(4)
1.521(4)
1.437(4)
1.404(4)
1.400(5)
1.431(4)
1.94(3)
1
1
1
2
5
2
5b
S –C
C –C (C –C )
1
1a
2
3
S –O (O )
O –C
1
1
1
2
4
F –C
O –C
2
3
4b
F –C
O –C
1
11
1
11a
3
5
N –H (N –H
)
O –C
NH? O
Angle
φ, deg
Angle
φ, deg
1
1
1
1
3
2
4
4b
3
5
N S C
102.5(3)
109.99(17)
105.45(18)
121.5(2)
126(2)
C O C (C O C )
110.3(3)
109.8(3)
108.28(19)
109.78(17)
110.0(3)
111.6(3)
110.7(2)
150.54
1
1
1a
3
2
3b
5
N S O (O )
C C C (C )
1
1
1
1a
3
2
5b
3b
2
5
C S O (O )
C C C (C C C )
1
1
1a
3b
2
5b
O S O
C C C
1
1
11
11a
2
3
2
S N H (H
)
O C C
1
1
11a
2
4
3b
H NH
97(3)
O C O
5
2
5b
3
5
2
C C C
110.9(3)
O C C
N–H? O
Angle
θ, deg
Angle
θ, deg
1
1
1
1
2
2
1
1a
1
1
2
1
1
1 2a
N S C F
180.00
50.9(5)
64.3(4)
64.87(16)
58.2(3)
63.7(4)
63.3(4)
O S C F (O S C F )
179.4(4)
172.4(3)
57.8(3)
52.6(3)
68.0(3)
52.6(3)
68.7(3)
1
1
1
3
2
5
3
3b
2
3
2
O S C F
C C C O (C C C O )
1
1
1
4b
3
5
2
3
3
2
N S C F
C O C C
1
1
1
3b
2
5
O S C F
C C C O
4
2
3
2
5b
2
5
C O C C
C C C O
3
2
4
3b
5b
2
3
C O C O
C C C O
5
b
3b
4
2
5
2
3
2
C O C O
C C C O
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 2 2008

314
MESHCHERYAKOV et al.
By means of the column chromatography we also
separated the isomer of compound VII, 3,7-bis(trifluoro-
methylsulfonyl)-1,5,3,7-dioxadiazocane (X).
A multitude of conformers is presumable for com-
pound X, but according to the published data the most
stable for the eight-memebered rings are boat-chair
conformers [5]. Calculations on the level B3LYP/6-
O
3
11G(d,p) showed that the lowest minimum on the
potential energy surface corresponds to the 3,7-boat-chair
CF SO2
N
N SO CF3
2
3
conformer Xa with nonequivalent CF groups: one
3
O
X
exocyclic and one endocyclic. For the six-membered
rings IV and V that we previously have investigated the
most stable conformers also possess CF groups of
1
3
Its H NMR spectrum at 25°C contains two broadened
signals at ~5.0 and 5.5 ppm and a single signal in the
different orientation [2, 3, 6]. Evidently just to this
19
conformer belong two signals in the low-temperature F
13
C NMR spectrum corresponding to both proton peaks
at ~84 ppm, in the region characteristics of NCH O
groups. The temperature dependence of H and F NMR
spectra of compound X was investigated (see the figure).
F NMR spectrum at –40°C indicates the presence of
two conformers in a ratio ~6:1,; therewith in the major
conformer the trifluoromethyl groups are nonequivalent,
whereas in the minor conformer they are equivalent.
NMR spectrum at –77.5 and –78.5 ppm. Conformer Xb
2
−1
1
19
is placed by 0.83 kcal mol higher on the energy scale,
and presumably the minor signal in the 19F NMR
spectrum at –78.3 ppm corresponds to two exocyclic CF3
groups of this conformer. The energy difference between
the major and minor conformers estimated from the
19
19
experimental ratio of signals intensity in the F NMR
Temperature dependence of H (a) and 19F (b) NMR spectra of 3,7-bis(trifluoro-methylsulfonyl)-1,5,3,7-dioxadiazocane
1
(
X) in acetonitrile-d3.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 2 2008

OXYMETHYLATION OF TRIFLUOROMETHANESULFONAMIDE
CF3
315
CF3
SO2
F3C SO2
N
F3C SO2
O2S
O
N
N
N
O
O
N
O
O
N
O
O
N
N
O
SO2
SO2 CF3
SO2
CF3
SO2
CF3
F3C
Xa
Xb
Xc
Xd
spectrum by an equation ΔE = –RT lnK at T 233 K was
According to NMR data under these conditions the main
reaction product was 5-trifluoro-methylsulfonyl-1,3-
dioxazinane (VI). A half of the reaction mixture was
separated, poured into ice water, thrice extracted with
ethyl acetate, the extract was washed with NaHCO3
−1
0
.83 kcal mol and exactly coincided with the calculated
value.
The energy of conformer Xc with both endo-
cyclic CF groups exceeds that of conformer Xa by
3
solution and dried with MgSO . On removing the solvent
−1
4
3
.5 kcal mol . Conformer 1,5-boat-chair Xd notwith-
the residue (about 7 g) was distilled in a vacuum. We
obtained 3.14 g of colorless liquid of bp 73–75°C (3 mm
Hg) containing by GLC data three principal components.
We failed to obtain pure 5-trifluoromethylsulfonyl-1,3-
dioxazinane (VI) by repeated distillation or fractionation.
The sample used for spectral measurements contained
standing the orientation of the CF groups is also less
3
feasible by the energy compared with Xa (by 1.3–2.7
−
1
kcal mol ).
EXPERIMENTAL
~
70% of target compound VI, ~20% of trifluoromethyl-
NMR spectra were registered on a spectrometer
sulfonamide, and ~10% of an impurity of unknown
structure.
1
Bruker DPX-400 at operating frequencies 400 ( H), 100
(13
C), and 376 ΜHz ( F), internal reference HMDS,
19
The remaining reaction mixture was gradually heated
from 20 to 80°C within 6 h, then it was cooled, poured
into ice water, thrice extracted with ethyl acetate, the
extract was washed with NaHCO solution and dried with
MgSO , the solvent was removed, part of the residue
1
chemical shifts are reported with respect to TMS ( H,
1
3
19
C) and CCl F ( F). The reaction progress was
3
monitored by TLC on plates with silica gel 60 F-254,
eluent hexane–ether, 1:2.
3
4
X-ray diffraction analysis was performed on a dif-
fractometer IPDS-2 (Stoe) at 293 K, graphite mono-
(
1 g) was subjected to column chromatography on silica
gel using eluents of growing polarity: hexane–ether, 2: 1
(360 ml), 1: 1 (100 ml), 1:2 (100 ml), 1: 3 (100 ml),
hexane–ether–acetone, 1:2:1 (360 ml). From the fractions
obtained we succeeded to isolate complex IX characteriz-
ed by X-ray diffraction analysis, and compound X
identified by means of NMR spectroscopy.
chromator, MoK radiation. Crystals orthorhombic (from
α
a mixture ether–hexane), C H F NO S, space group
8
14
3
6
Ama2, Z 4, a 19.0293(6), b 12.0000(12), c 5.616(3) Å, V
3
3
1
282.4(7) Å , ρ 1.602 g/cm . The cell parameters were
estimated from 4038 reflections with 2.1 < θ < 25.0°.
The structure was solved by the direct method [7] and
refined in the full-matrix least-squares method in the
anisotropic approximation for nonhydrogen atoms and
in isotropic approximation for hydrogen atoms [8]. The
5
-Trifluoromethylsulfonyl-1,3-dioxazinane (VI).
1
H NMR spectrum (CD CN), δ, ppm: 5.16 s (2H,
3
13
OCH O), 5.26 s (4H, OCH N).
C NMR spectrum
2
2
19
(CD CN), δ, ppm: 78.95 (OCN), 95.28 (OCO). F NMR
3
final values of divergence factors are R 0.0399, R 0.1070
w
spectrum (CD CN), δ, ppm: –77.77 br.s.
3
for 971 reflections with I > 2σ(I). Quantum-chemical
calculations are carried out with the use of GAUSSIAN-
Complex 2,4,8,10-tetraoxospiro[5,5]undecene–
trifluoromethanesulfonamide (IX). H NMR spectrum
1
9
8 software [9].
(
CD CN), δ, ppm: 3.72 s (8H, OCH C), 4.76 s (4H,
3
2
1
3
Reaction of trifluoromethanesulfonamide with
OCH O), 6.66 br.s (2H, NH ).
C NMR spectrum
2
2
CH O in ethyl acetate. To a mixture of 5 g (0.034 mol)
(CD CN), δ, ppm: 34.44 (CCC), 70.80 (OCC), 95.02
3
2
19
of trifluoromethanesulfonamide (I) and 8 g (0.268 mol)of
paraformaldehyde in 75 ml of ethyl acetate at vigorous
stirring was slowly added 24 ml of concn. H SO , and
(OCO), 120.64 q (CF , J 318.8 Hz). F NMR spectrum
3
(CD3CN), δ, ppm: –78.99.
2
4
3,7-Bis(trifluoromethylsulfonyl)-1,5,3,7-dioxa-
1
the mixture was stirred at room temperature for 6 h.
diazocane (X). H NMR spectrum (CD CN), δ, ppm:
3
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 2 2008

316
MESHCHERYAKOV et al.
4
.98, 5.49 m (CH2). 13C NMR spectrum (CD CN), δ,
7. Sheldrick, G.M., SHELXS-97. Program for Crystal
Structure Solution, Göttingen, 1997.
3
19
ppm: 84.40 (CH ), 120.34 q (CF , J 323.4 Hz). F NMR
spectrum (CD CN), δ, ppm: –77.87 br.s.
2
3
8
. Sheldrick, G.M., SHELXL-97. Program, for Crystal
Structure Refinement, Göttingen, 1997.
3
The study was carried out under a financial support
of the Russian Foundation for Basic Research (grant no.
0
9
. Frisch, M.J., Trucks, G.W., Schlegel, H.B., Scuseria, G.E.,
Robb, M.A., Cheeseman, J.R., Zakrzewski, V.G., Montgo-
mery, J.A., Stratmann, R.E., Burant, J.C., Dapprich, S.,
Millam, J.M., Daniels, A.D., Kudin, K.N., Strain, M.C.,
Farkas, O., Tomasi, J., Barone, V., Cossi, M., Cammi, R.,
Mennucci, B., Pomelli, C., Adamo, C., Clifford, S.,
Ochterski, J., Petersson, G.A., Ayala, P.Y., Cui, Q.,
Morokuma, K., Malick, D.K., Rabuck, A.D., Raghava-
chari, K., Foresman, J.B., Cioslowski, J., Ortiz, J.V.,
Stefanov, B.B., Liu, G., Liashenko, A., Piskorz, P.,
Komaromi, I., Gomperts, R., Martin, R.L., Fox, D.J., Keith, T.,
Al-Laham, M.A., Peng, C.Y., Nana-yakkara, A., Gonza-
lez, C., Challacombe, M., Gill, P.M.W., John-son, B.,
Chen, W., Wong, M.W., Andres, J. L., Gonzalez, C., Head-
Gordon, M., Replogle, E.S., and Pople, J.A., Gaussian 98,
Revision A.6, Gaussian, Inc., Pittsburgh, PA, 1998.
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