Desulfurizing agent for thioamides

Article abstract of DOI:10.1007/s11172-021-3096-4

Thioamides treated with thionyl chloride in an ionic liquid were successfully converted into amides.

Full text of DOI:10.1007/s11172-021-3096-4

Russian Chemical Bulletin, International Edition, Vol. 70, No. 2, pp. 383—385, February, 2021
383
Desulfurizing agent for thioamides
A. V. Polushina,a I. V. Zavarzin,a M. M. Krayushkin,a G. M. Rodionova,b and V. N. Yarovenkoa
aN. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
47 Leninsky prosp., 119991 Moscow, Russian Federation.
E-mail: yarov@ioc.ac.ru
bI. M. Sechenov First Moscow State Medical University, Ministry of Healthcare of the Russian Federation,
Build. 2, 8 ul. Trubetskaya, 119991 Moscow, Russian Federation
Thioamides treated with thionyl chloride in an ionic liquid were successfully converted
into amides.
Key words: thioamides, ionic liquids, thionyl chloride, amides.
Thioamides are widely used in the synthesis of various
compounds, including different heterocyclic structures.1,2
Desulfurization of available thioamides is one of the con-
venient approaches to the preparation of amides, which
are also known to be of considerable interest in organic
and bioorganic chemistry.
provided that the reaction atmosphere is not inert (Scheme 2).
Apparently, the process should be accelerated by electro-
philic catalysts. However, we were unable to find inform-
ation on the reactions of thionyl chloride in ionic liquids,
which prompted us to study the reaction of this agent with
thioamides.
The transformation of a thioamide group into the
amide can formally be considered as a process of oxidative
desulfurization, which begins with the attack on the sulfur
atom of the thiocarbonyl group by an electrophilic or
radical species. It is believed, for example, that in the
oxidation of thioamides with hydrogen peroxide, the form-
ation of the amide is preceded by the stage of the formation
of the sulfinyl group3 (Scheme 1).
Scheme 2
Earlier,6 we have developed a convenient method for
the synthesis of monothiooxamides, which consists in the
reaction of α-chloroacetamides with pre-prepared solu-
tions of elemental sulfur in amines, and showed the pos-
sibility to synthesize various compounds on their basis,
including arenes and pyridines 1a—d.7 The desulfurization
reaction was studied based on these products.
Scheme 1
Expanding the scope of reactions allowing the activa-
tion of an available thiocarbonyl group under the action
of an electrophilic agent in order to convert a thioamide
fragment into the amide one seems to be an attractive
problem.
We assumed that thionyl chloride in an ionic liquid
may be a convenient activating and, as a consequence,
desulfurizing reagent. There are literature data on the
reaction of thioamides with thionyl chloride in different
solvents, which leads to the mixtures of amides with other
products4 or, in some cases, is inefficient.5 In our opinion,
the reaction of the thiocarbonyl group with thionyl chlor-
ide can lead to an unstable compound A, the hydrolysis of
which results in the formation of the carbonyl group,
We have shown for the first time that the conversion
of monothiooxamides 1a—d to oxalic acid amides 2a—d
can be successfully accomplished within 2—3 min at room
temperature by treatment with thionyl chloride in the ionic
liquid 1-butyl-3-methylimidazolium hexafluorophosphate
(Scheme 3).
Note that the reaction of monothiooxamides with
thionyl chloride without using an ionic liquid or in the
presence of Lewis acids (AlCl3, SnCl4) both in solvents
(CH2Cl2, ClCH2CH2Cl) and without them does not give
oxalic acid amides, rather it leads to the formation of
multicomponent mixtures.
We have demonstrated the general nature of this
approach (Scheme 4) and extended it to the desulfuriza-
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 383—385, February, 2021.
1066-5285/21/7002-0383 © 2021 Springer Science+Business Media LLC

Polushina et al.
384
Russ. Chem. Bull., Int. Ed., Vol. 70, No. 2, February, 2021
Scheme 3
Table 1. Yields of amides 2a—d, 5a,b, 8,
11a,b, and 14a—c obtained by the reactions
of the corresponding thioamides with thio-
nyl chloride in an ionic liquid
Com-
pound
Yield
(%)
Com-
pound
Yield
(%)
2a
2b
2c
2d
5a
5b
70
73
74
70
68
57
8
75
65
69
74
67
70
1, 2
a
X
Y
NR1R2
Morpholin-4-yl
NHPh
NHPh
Morpholin-4-yl
R3
H
H
H
NO2
R4
H
Cl
H
11a
11b
14a
14b
14c
CH
CH
CH
N
NO2
NO2
NO2
H
b
c
d
H
Reagents and conditions: i. SOCl2, 1-butyl-3-methylimidazolium
hexafluorophosphate, 2—3 min, room temperature.
The yields of amides obtained by the reactions of
thioamides with thionyl chloride in the ionic liquid are
summarized in Table 1.
It can be suggested that the new desulfurizing agent
will be of interest in organic synthesis in the cases
when thioamide derivatives are more readily available
than amides, provided that the latter are the target com-
pounds.
tion of readily available thioamides 4a,b (see Ref. 8)
and 7 (see Ref. 9), as well as thiooxamides 10a,b (see
Ref. 10).
The method allows one to "remove" sulfur from the
dithioester group of thiooxamides 13a—c under mild
conditions (see Ref. 8) to form acid thioesters 14a—c
(Scheme 5).
Scheme 4
4, 5, 10, 11: NR1R2 = morpholin-4-yl (a), NHPh (b)
Scheme 5
R = H (a), Cl (b), Br (c)

Desulfurizing reagent for thioamides
Russ. Chem. Bull., Int. Ed., Vol. 70, No. 2, February, 2021
385
1H NMR, δ: 3.90 (s, 4 H, 2 CH2); 4.30 (s, 4 H, 2 CH2); 8.20
(s, 2 H, Ar); 8.40 (s, 2 H, Ar); 8.65 (s, 1 H, Ar). MS, m/z: 219 [M]+.
2-Oxo-N,2-diphenylacetamide (11b). White crystals, the yield
was 69%, m.p. 62—63 °C (cf. Ref. 15: m.p. 62—63 °C). 1H NMR,
δ: 7.35 (s, 2 H, Ar); 7.60 (s, 2 H, Ar); 7.75 (s, 1 H, Ar); 7.90
(s, 1 H, Ar); 8.30 (s, 2 H, Ar); 8.45 (s, 2 H, Ar); 10.45 (s, 1 H, NH).
MS, m/z: 225 [M]+.
S-Methyl 2-oxo-2-(phenylamino)ethanethioate (14a). White
crystals, the yield was 74%, m.p. 241—243 °C. 1H NMR, δ: 2.35
(s, 3 H, Me); 7.60 (s, 1 H, Ar); 7.85 (s, 2 H, Ar); 8.00 (s, 1 H,
Ar); 8.15 (s, 1 H, Ar); 10.70 (s, 1 H, NH). MS, m/z: 195 [M]+.
Found (%): С, 55.44; H, 4.80; N, 7.10. С9H9NO2S. Calculat-
ed (%): С, 55.37; H, 4.65; N, 7.17.
S-Methyl 2-[(4-chlorophenyl)amino]-2-oxoethanethioate
(14b). White crystals, the yield was 67%, m.p. 168—170 °C.
1H NMR, δ: 2.30 (s, 3 H, Me); 7.65 (s, 1 H, Ar); 7.80 (s, 2 H,
Ar); 8.15 (s, 1 H, Ar); 10.60 (s, 1 H, NH). MS, m/z: 230 [M]+.
Found (%): С, 47.15; H, 3.42; Сl, 15.58; N, 6.15; S, 13.79.
С9H8ClNO2S. Calculated (%): С, 47.06; H, 3.51; Cl, 15.44;
N, 6.10; S, 13.96.
S-Methyl 2-[(4-bromophenyl)amino]-2-oxoethanethioate
(14с). White crystals, the yield was 70%, m.p. 184—186 °C.
1H NMR, δ: 2.33 (s, 3 H, Me); 7.70 (s, 1 H, Ar); 7.80 (s, 2 H,
Ar); 8.20 (s, 1 H, Ar); 10.85 (s, 1 H, NH). MS, m/z: 274 [M]+.
Found (%): С, 39.36; H, 2.98; Br, 29.02; N, 5.03; S, 11.84.
С9H8BrNO2S. Calculated (%): С, 39.43; H, 2.94; Br, 29.15;
N, 5.11; S, 11.70.
Experimental
1H NMR spectra were recorded on a Bruker AC-300 spectro-
meter in DMSO-d6. Mass spectra were recorded on a Varian
MAT CH-6 instrument (70 eV) with direct sample injection into
the radiation source, control voltage 1.75 kV. Melting points were
measured on a Boetius heating stage and were not corrected.
TLC on Merck Silica gel 60 F254 plates was used to analyze all
reaction mixtures and control the purity of the isolated products.
Synthesis of oxoacetamides (general procedure). Thioamide
(0.1 mmol) was dissolved in a minimal amount of an ionic
liquid (1-butyl-3-methylimidazolium hexafluorophosphate),
followed by the addition of thionyl chloride (0.15 mmol). After
2—4 min, the mixture was extracted with benzene or diethyl
ether (3×5 mL), the organic layer was washed with water, the
solvent was evaporated in vacuo. The product was purified
on a chromatographic plate (eluent petroleum ether—ethyl
acetate, 3 : 1).
2-Morpholin-4-yl-N-(2-nitrophenyl)-2-oxoacetamide (2a).
White crystals, the yield was 70%, m.p. 147—149 °C. 1H NMR,
δ: 3.60 (d, 2 H, СH2, J = 4.6 Hz); 3.80 (d, 4 H, 2 СH2, J = 4.4 Hz);
3.90 (s, 2 H, CH2); 7.45 (s, 1 H, Ar); 7.85 (s, 2 H, Ar); 8.05
(s, 1 H, Ar); 11.25 (s, 1 H, NH). MS, m/z: 279 [M]+. Found (%):
С, 51.74; H, 4.52; N, 15.21. С12H13N3O5. Calculated (%): С, 51.61;
H, 4.69; N, 15.05.
N-(4-Chlorophenyl-2-nitro)-N´-phenylethanediamide (2b).
White crystals, the yield was 73%, m.p. 163—165 °C. 1H NMR,
δ: 7.40 (s, 1 H, Ar); 7.60 (s, 3 H, Ar); 7.90 (s, 2 H, Ar); 8.20
(s, 1 H, Ar); 8.35 (s, 1 H, Ar); 10.90 (s, 1 H, NH); 11.60 (s, 1 H,
NH). MS, m/z: 319 [M]+. Found (%): С, 52.74; H, 3.10;
N, 13.27. С14H10ClN3O4. Calculated (%): С, 52.60; H, 3.15;
N, 13.14.
The authors express their gratitude to the program for
the development of scientific schools of the N. D. Zelinsky
Institute of Organic Chemistry of the Russian Academy
of Sciences.
N-(2-Nitrophenyl)-N´-phenylethanediamide (2c). White crys-
tals, the yield was 74%, m.p. 287—289 °C. 1H NMR, δ: 7.20
(s, 1 H, Ar); 7.45 (s, 3 H, Ar); 7.85 (s, 3 H, Ar); 8.15 (s, 1 H, Ar);
8.20 (s, 1 H, Ar); 10.80 (s, 1 H, NH); 11.75 (s, 1 H, NH). MS,
m/z: 285 [M]+. Found (%): С, 58.81; H, 3.94; N, 14.62.
С14H11N3O4. Calculated (%): С, 58.95; H, 3.89; N, 14.73.
2-Morpholin-4-yl-N-(5-nitropyridin-3-yl)-2-oxoacetamide
(2d). White crystals, the yield was 70%, m.p. 188—190 °C.
1H NMR, δ: 3.80 (s, 6 H, 3 СH2); 4.20 (s, 2 H, СH2); 8.00 (s, 1 H,
HPy); 8.35 (s, 1 H, HPy); 8.55 (s, 1 H, HPy); 11.80 (s, 1 H, NH).
MS, m/z: 280 [M]+. Found (%): С, 47.03; H, 4.37; N, 19.82.
С11H12N4O5. Calculated (%): С, 47.15; H, 4.32; N, 19.99.
2-Morpholinocarbonyl-1H-benzimidazole (5a). White crys-
tals, the yield was 68%, m.p. 181—183 °C (cf. Ref. 11: m.p.
181—182 °C). 1H NMR, δ: 3.90 (s, 2 H, CH2); 4.10 (s, 2 H,
CH2); 4.25 (s, 4 H, 2 CH2); 7.40 (s, 2 H, Ar); 7.80 (s, 2 H, Ar);
10.90 (s, 1 H, NH). MS, m/z: 231 [M]+.
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Received May 7, 2020;
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accepted October 1, 2020
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