Oxidation of Thioamides to Amides with Tetrachloro- and Tetrabromoglycolurils

Article abstract of DOI:10.1134/S1070428019120108

Tetrabromo- and tetrachloroglycolurils have been shown to act as good oxidants capable of converting thioamides to the corresponding amides. This approach offers such advantages as good yields (81–99%), short reaction times (10–25 min), simple workup procedure, and environmental safety.

Full text of DOI:10.1134/S1070428019120108

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2019, Vol. 55, No. 12, pp. 1874–1877. © Pleiades Publishing, Ltd., 2019.
Russian Text © The Author(s), 2019, published in Zhurnal Organicheskoi Khimii, 2019, Vol. 55, No. 12, pp. 1883–1887.
Oxidation of Thioamides to Amides
with Tetrachloro- and Tetrabromoglycolurils
I. Boudebouza,* S. Arrousa, and I. V. Parunova
a National Research Tomsk State University, Tomsk, 634050 Russia
*e-mail: imene_boudebouz@yahoo.ca
Received May 31, 2019; revised July 10, 2019; accepted October 24, 2019
Abstract—Tetrabromo- and tetrachloroglycolurils have been shown to act as good oxidants capable of con-
verting thioamides to the corresponding amides. This approach offers such advantages as good yields (81–99%),
short reaction times (10–25 min), simple workup procedure, and environmental safety.
Keywords: amide, glycoluril, oxidation, tetrabromoglycoluril, tetrachloroglycoluril, thioamide, thiohydantoin.
DOI: 10.1134/S1070428019120108
The transformation of thioamides to the correspond-
ing amides is an important reaction in organic chemistry.
Undoubtedly, amides constitute a fundamental class
of organic compounds, as they can be dehydrated to
nitriles, hydrolyzed to carboxylic acids, and converted
to amines with one fewer carbon atom via the Hofmann
rearrangement. Amide derivatives are widely used as
agrochemicals and insecticides and in the synthesis
of polymers and pharmaceuticals. A huge number of
amides are used as biologically active compounds [1, 2],
constituting about 25% of commercially available
drugs [3, 4]. Thiocarbonyl compounds can be con-
verted to their oxygen analogs using such reagents as
benzeneseleninic anhydride [5], DMDO/iodine [6],
NO+-containing compounds [7], clay-supported
iron(III) nitrate [8], 4-nitrobenzaldehyde/trimethylsilyl
trifluoromethanesulfonate [9], 2-nitrobenzenesulfonyl
chloride/potassium superoxide [10], MnO2 [11],
Bu4N+IO4– [12], and wet silica-supported potassium
permanganate [13]. However, some of these methods
suffer from some drawbacks, including long reaction
time, low yield [10], toxic or expensive reagents [5, 7],
and laborious experimental procedure [5, 7, 9].
[14]. Examples are N-haloglycolurils such as tetra-
bromoglycoluril (TBG) and tetrachloroglycoluril
(TCG) where the halogen atoms are linked to nitrogens.
There are no published data on the oxidation of thio-
amides with TBG or TCG. Herein, we describe a simple
procedure for the oxidation of thioamides with TBG
and TCG at 40°C (Scheme 1).
Scheme 1.
S
O
TBG or TCG, ROH, 40°C
HN
NH
HN
NH
The oxidation of cyclic thioureas 1a–6a to the
corresponding oxo derivatives was not described in the
literature. An exception is compound 4a which was
previously subjected to desulfurization with tetrabutyl-
ammonium periodate [16] and trans-3,5-bis(hydro-
peroxy)-3,5-dimethyl-1,2-dioxolane [17]. Oxygen-con-
taining analogs 1b–6b possess a number of practically
useful properties [18–21]. We accomplished mild and
efficient transformation of cyclic thioureas 1a–6a to
ureas 1b–6b using TBG and TCG which were prepared
as described in [22, 23]. The reactions were carried
out in ethanol or methanol at 40°C for 10–25 min, and
the yields were 81–99% (Table 1). The products were
easily isolated by filtering of the reaction mixture and
removing the solvent from the filtrate.
N-Halogenated compounds are widely used in
organic synthesis and chemistry of natural compounds
Br
Br
Cl
Cl
N
N
N
N
N
O
O
O
O
N
N
N
In the oxidation of 1a with TBG, the yield of 1b
was 95% in 15 min; the oxidation of compound 5a
having two C=S groups was complete in 25 min, and
Br
Br
Cl
Cl
TBG
TCG
1874

OXIDATION OF THIOAMIDES TO AMIDES
1875
Table 1. Oxidation of cyclic thioureas 1a–6a to ureas 1b–6b with TBG and TCG
Reaction time, min
Yield, %
(TBG/TCG)
Substrate
Product
Solvent
EtOH
Reference
(TBG/TCG)
S
O
HN
Ph
NH
HN
NH
10/15
99/95
90/86
[18, 24]
Ph
O
O
Ph
1a
Ph
1b
S
O
Ph
Ph
HN
Ph
N
HN
N
EtOH
10/20
[25]
Ph
O
O
Ph
Ph
2a
2b
Ph
Ph
N
S
Ph
Ph
N
O
EtOH
EtOH
10/15
10/20
91/82
92/88
[20, 26]
[27]
NH
NH
NH
NH
N
3a
N
3b
S
O
HN
HN
O
O
O
O
4a
4b
H
N
H
N
H
N
H
N
S
S
S
S
O
O
O
O
EtOH
15/25
20/25
96/92
90/81
[28]
[28]
N
H
N
H
N
H
N
H
5a
5b
Ph
Ph
H
N
H
N
H
N
H
N
MeOH
N
H
N
H
N
H
N
H
Ph
Ph
6a
6b
the yield of 5b was 92%. Tetrabromoglycoluril ensured
higher yields (90–99%) and shorter reaction times
(10–20 min). In all cases, 0.4 mol of TBG or TCG per
mole of 1a–6a was used. The efficiency of TBG and
TCG in comparison to other reagents [16, 17] was
demonstrated in the oxidation of 2-thiobarbituric acid
(4a) to barbituric acid (4b) (Table 2).
to the corresponding oxygen analogs. Tetrabromo-
glycoluril is more effective than tetrachloroglycoluril
in terms of yield and reaction time.
EXPERIMENTAL
1
The H and 13C NMR spectra were recorded on
a Bruker Avance 400 III HD spectrometer (USA) at
400.17 and 100.63 MHz, respectively, using DMSO-d6
as solvent and tetramethylsilane as internal standard.
The IR spectra were recorded in the range 4000–
400 cm–1 on a Bruker Tensor 27 FTIR spectrometer
Thus, tetrabromo- and tetrachloroglycolurils are
highly efficient, mild, accessible, and environmentally
benign oxidants ensuring experimentally simple and
convenient transformation of thioamides and thioureas
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 55 No. 12 2019

BOUDEBOUZ et al.
Table 2. Oxidation of 2-thiobarbituric acid (4a) to barbituric acid (4b) with different oxidants
1876
Oxidant
Solvent, temperature
Reaction time, min Yield, %
TBG
TCG
EtOH, 40°C
10
20
92
88
86
85
EtOH, 40°C
Tetrabutylammonium periodate
CH2Cl2–MeCN (1:1), r.t.
MeCN, r.t.
120
10
trans-3,5-Bis(hydroperoxy)-3,5-dimethyl-1,2-dioxolane
equipped with an ATR accessory (resolution 4 cm–1;
scan number 16); samples were prepared as KBr discs.
The melting points were measured in open capillaries
with a Buchi melting point apparatus.
Pyrimidine-2,4,6(1H,3H,5H)-trione (4b). White
solid, mp 245–247°C [27]. IR spectrum, ν, cm–1:
1
3189 (NH), 1751, 1684 (C=O). H NMR spectrum, δ,
ppm: 11.12 s (2H, NH), 3.45 s (2H, CH2). 13C NMR
spectrum, δC, ppm: 168.24, 152.13, 40.47.
Tetrabromo- and tetrachloroglycolurils were pre-
pared as described in [29] by bromination or chlorina-
tion of glycoluril with molecular bromine or chlorine,
respectively.
Perhydroimidazo[4,5-d]imidazole-2,5-dione
(5b). White solid, mp >300°C [28]. IR spectrum, ν,
cm–1: 3203 (N–H), 2866 (C–H), 1679 (C=O). 1H NMR
spectrum, δ, ppm: 7.18 s (4H, NH), 5.16 s (2H, CH).
13C NMR spectrum, δC, ppm: 161.21, 65.05.
General procedure for the oxidation of thioureas
1a–6a to ureas1b–6b. Tetrabromo- and tetrachloro-
glycoluril, 0.4 mol, was added to a solution of 1 mol
of 1a–6a in 10 mL of ethanol or methanol (Table 1).
During the addition, the mixture turned light yellow.
It was stirred for 10–25 min at 40°C until the yellow
color disappeared and filtered from the precipitate of
glycoluril, the filtrate was concentrated, and the
solid product was filtered off and washed with water.
The products were identified by comparing their
physical properties and spectral characteristics
with published data. The yields of 1b–6b are given
in Table 1.
3a,6a-Diphenylperhydroimidazo[4,5-d]imid-
azole-2,5-dione (6b). White solid, mp 373–378°C [28].
IR spectrum, ν, cm–1: 3221 (N–H), 2829 (C–H), 1676
(C=O), 1491 (C=C). 1H NMR spectrum, δ, ppm: 7.75 s
(4H, NH), 7.05 m (10H, Harom). 13C NMR spectrum, δC,
ppm: 161.18, 138.73, 128.23, 127.80, 127.48, 82.24.
CONFLICT OF INTERESTS
The authors declare the absence of conflict of interests.
REFERENCES
5,5-Diphenylimidazolidine-2,4-dione (1b). White
solid, mp 293–298°C [18, 24]. IR spectrum, ν, cm–1:
3198 (N–H), 3070 (C–H), 1714, 1694 (C=O), 1493
(C=C) 1241 (C–N). 1H NMR spectrum, δ, ppm: 11.12 s
(1H, NH), 9.33 s (1H, NH), 7.32–7.42 m (10H, Harom).
13C NMR spectrum, δC, ppm: 175.29, 156.46, 140.36,
128.98, 127.04, 70.67.
1. Greenberg, A., Breneman, C.M., and Liebman, J.F., The
Amide Linkage: Structural Significance in Chemistry,
Biochemistry, and Materials Science, New York: Wiley,
2000.
2. Humphrey, J.M. and Chamberlin, A.R., Chem. Rev. 1997,
vol. 97, p. 2243.
https://doi.org/10.1021/cr950005s
3. Lundberg, H., Tinnis, F., Selander, N., and Adolfsson, H.,
Chem. Soc. Rev., 2014, vol. 43, p. 2714.
3,5,5-Triphenylimidazolidine-2,4-dione (2b).
White solid, mp 200–203°C [25]. IR spectrum, ν,
cm–1: 3178 (N–H), 3103 (C–H), 1714, 1772 (C=O),
1
https://doi.org/10.1039/C3CS60345H
1394 (C–N), 1489 (C=C). H NMR spectrum, δ, ppm:
13
4. Chaudhari, P.S., Salim, S.D., Sawant, R.V., and
Akamanchi, K.G., Green Chem., 2010, vol. 12, p. 1707.
https://doi.org/10.1039/c0gc00053a
5. Cussans, N.J., Ley, S.V., and Barton, D.H.R., J. Chem.
Soc., Perkin Trans. 1, 1980, p. 1650.
https://doi.org/10.1039/P19800001650
6. Mikolajczyk, M. and Luczak, J., Synthesis, 1975, p. 114.
https://doi.org/10.1055/s-1975-23679
7. Jorgensen, K.A., Ghattas, A.B.A.G., and Lawesson, S.O.,
Tetrahedron, 1982, vol. 38, p. 1163.
9.98 s (1H, NH), 7.39–7.51 m (15H, Harom). C NMR
spectrum, δC, ppm: 172.80, 154.68, 140.01, 132.14,
129.42, 129.17, 128.41, 127.37, 127.25, 69.62.
5,6-Diphenyl-1,2,4-triazin-3(2H)-one (3b). White
solid, mp 170–174°C [20, 26]. IR spectrum, ν, cm–1:
3197 (N–H), 1659 (C=O), 1561 (C=C), 1445 (C=N),
1
1369 (C–N). H NMR spectrum, δ, ppm: 8.75 s (1H,
NH), 7.25–7.45 m (10H, Harom). 13C NMR spectrum,
δC, ppm: 167.78, 153.87, 142.82, 136.22, 134.98,
131.30, 129.78, 129.34, 129.28, 128.66, 128.50.
https://doi.org/10.1016/0040-4020(82)85099-0
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 55 No. 12 2019

OXIDATION OF THIOAMIDES TO AMIDES
1877
8. Chalais, S., Cornelis, A., Laszlo, P., and Mathy, A.,
Tetrahedron Lett., 1985, vol. 26, p. 2327.
Poupaert, J.H., and Lambert, D.M., J. Med. Chem., 2006,
vol. 49, p. 872.
https://doi.org/10.1016/S0040-4039(00)95088-3
https://doi.org/10.1021/jm050484f
9. Ravindranathan, T., Chavan, S.P., Awachat, M.M.,
and Kelkar, S.V.A., Tetrahedron Lett., 1995, vol. 36,
p. 2277.
20. Pooja, M., Suroor, A.K., Tauseef, B., Surajpal, V.,
Darpan, K., and Ozair, A., Acta Pol. Pharm., 2009,
vol. 66, p. 379.
https://doi.org/10.1016/0040-4039(95)00189-J
21. Addiscott, T.M. and Thomas, V.H., Chem. Ind.,
10. Kim, Y.H., Chung, B.C., and Chang, H.S.,
Tetrahedron Lett., 1985, vol. 26, p. 1079.
1979, p. 29.
22. Frank, S., Alfred, H., and Irving, R., J. Org. Chem., 1960,
vol. 25, p. 660.
https://doi.org/10.1016/S0040-4039(00)98517-4
11. Radha, R.R., Rahman, M.F., and Bhalerao, U.T.,
Tetrahedron, 1992, vol. 48, p. 1953.
https://doi.org/10.1016/S0040-4020(01)88517-3
12. Pourali, A.R., Monatsh. Chem., 2005, vol. 136, p. 733.
https://doi.org/10.1021/jo01074a619
23. Yagovkin, A.Y., Bakibaev, A.A., and Filimonov, V.D.,
USSR Inventor’s Certificate no. 1675300, 1991.
24. Fernand,A.G., Salomé, S.D.K., Coco, N.K., Giulio, G.M.,
Didier, M.L., Géorges, C.A., Moudachirou, M., and
Jacques, H.P., Afr. J. Pure Appl. Chem., 2011,
vol. 5, p. 168.
25. Giulio, G.M., Johan, W., Gerhard, K.E.S., Wolfgang, P.,
Jacques, H.P., and Didier, M.L., J. Med. Chem., 2005,
vol. 48, p. 7486.
https://doi.org/10.1007/s00706-005-0289-8
13. Masoud, N.E., Majid, M., Iraj, M.B., and
Mohammad, H.B., Phosphorus, Sulfur Silicon Relat.
Elem., 2009, vol. 184, p. 141.
https://doi.org/10.1080/10426500802080865
14. Kolvari, E., Choghamarani, A.G., Salehi, P., Shirini, F.,
and Zolfigol, M.A., J. Iran. Chem. Soc., 2007, vol. 4,
p. 126.
https://doi.org/10.1007/BF03245963
15. Paterson, O., US Patent no. 3071591, 1963.
doi 10.1021/jm0503906
26. Mara, E.F.B., Hugo, T.S.B., Marciana, P.U., Carla, C.C.,
and Marcelo, S., J. Braz. Chem. Soc., 2008, vol. 19, p. 909.
https://doi.org/10.1590/S0103-50532008000500015
16. Pourali, A.R., Monatsh. Chem., 2005, vol. 136, p. 733.
27. Mohammadpoor, B., Memarian, H.R., Hajipour, A.R.,
and Bahrami, K., Bull. Korean Chem. Soc., 2003,
vol. 24, p. 1002.
https://doi.org/10.1007/s00706-005-0289-8
17. Azarifar, D. and Golbaghi, M., J. Sulfur Chem., 2016,
vol. 37, p. 1.
https://doi.org/10.5012/bkcs.2003.24.7.1002
https://doi.org/10.1080/17415993.2015.1082181
18. Abhijit, K., Sampada, J., andRajesh, O.,E-J. Chem., 2011,
vol. 8, p. S47.
28. Esmail, V., Mehdi, D.E., Zahra, A., and Morteza, R.,
Green Chem. Lett. Rev., 2014, vol. 7, p. 119.
https://doi.org/10.1080/17518253.2014.895865
https://doi.org/10.1155/2011/159430
19. Muccioli, G.G., Wouters, J., Charlier, C., Scriba, G.K.E.,
Pizza, T., Pace, P.D., Martino, P.D., Poppitz, W.,
29. Slezaka, F., Irsch, L., and Sen, I., J. Org. Chem., 1960,
vol. 25, p. 660.
https://doi.org/10.1021/jo01074a619
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 55 No. 12 2019