Willgerodt-Kindler reaction of arylglyoxals with amines and sulfur in aqueous media: A simple and efficient synthesis of -ketothioamides

Article abstract of DOI:10.1080/17415993.2012.757614

A simple and efficient method for the synthesis of -ketothioamides via the Willgerodt-Kindler reaction is developed. Reactions were carried out between arylglyoxal hydrates, amines and elemental sulfur in water at 80°C to afford corresponding -ketothioamides in good to high yields in a short reaction time.

Full text of DOI:10.1080/17415993.2012.757614

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Willgerodt–Kindler reaction of
arylglyoxals with amines and sulfur in
aqueous media: a simple and efficient
synthesis of α-ketothioamides
Bagher Eftekhari-Sis a , Saleh Vahdati-Khajeh a , S. Motahhareh
Amini a , Maryam Zirak b & Mahnaz Saraei b
a Department of Chemistry, University of Maragheh, PO Box
55181-83111, Maragheh, Iran
b Department of Chemistry, Payame Noor University, PO Box
19395-3697, Tehran, Iran
Version of record first published: 22 Jan 2013.
To cite this article: Bagher Eftekhari-Sis , Saleh Vahdati-Khajeh , S. Motahhareh Amini , Maryam
Zirak & Mahnaz Saraei (2013): Willgerodt–Kindler reaction of arylglyoxals with amines and sulfur in
aqueous media: a simple and efficient synthesis of α-ketothioamides, Journal of Sulfur Chemistry,
DOI:10.1080/17415993.2012.757614
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Journal of Sulfur Chemistry, 2013
http://dx.doi.org/10.1080/17415993.2012.757614
Willgerodt–Kindler reaction of arylglyoxals with amines and
sulfur in aqueous media: a simple and efficient synthesis of
α-ketothioamides
Bagher Eftekhari-Sisa*, Saleh Vahdati-Khajeha, S. Motahhareh Aminia, Maryam Zirakb and
Mahnaz Saraeib
aDepartment of Chemistry, University of Maragheh, PO Box 55181-83111, Maragheh, Iran; bDepartment
of Chemistry, Payame Noor University, PO Box 19395-3697, Tehran, Iran
(Received 16 September 2012; final version received 6 December 2012)
A simple and efficient method for the synthesis of α-ketothioamides via the Willgerodt–Kindler reaction is
developed. Reactions were carried out between arylglyoxal hydrates, amines and elemental sulfur in water
at 80◦C to afford corresponding α-ketothioamides in good to high yields in a short reaction time.
Keywords: Willgerodt–Kindler reaction; α-ketothioamides; arylglyoxals; water; sulfur
1. Introduction
Carrying out organic reactions in water have attracted increasing interest in the last few decades
(1–3), not only because water is one of the most abundant and cheap solvents and makes the
reactions safer, easier to handle and environmentally amenable (4, 5), but also because reactions
inwatershow different reactivityand selectivity in comparisonwithconventionalorganicsolvents.
The Willgerodt–Kindler reaction is one of the most important methods for the construction
of thioamide moiety ((6, 8) and references cited therein, (7)), which exhibit a wide range of
biological activities such as pesticidal (9), fungicidal (10), insecticidal (11), antioxidant (12) and
antitubercular (13) activities.Also, thioamides have widely been used in the field of peptide chem-
istry (14–16), polymers (17, 18) and as building blocks in organic synthesis (19–22), especially
*Corresponding author. Emails: eftekharisis@maragheh.ac.ir; eftekhari.sis@gmail.com
© 2013 Taylor & Francis

2
B. Eftekhari-Sis et al.
for the synthesis of five- and six-membered heterocycles (23–28). A number of methods are avail-
able in the literature for the preparation of thioamides, such as thionation of amides (29–35) and
Friedel–Crafts reaction of aromatic compounds with KSCN (36). However, α-ketothioamides
were isolated in very low yields as by-products in the Willgerodt–Kindler reaction of aryl methyl
ketones (37, 38); modified Willgerodt–Kindler reaction using IR energy was reported to produce
α-ketothioamides in 12–67% yields, in which also the corresponding aryl methyl thioamides
were isolated in 0–42% yields (39). Also, α-ketothioamides were prepared by a number of other
limited different approaches (40–42), which have some disadvantages, such as limited scope of
the products, expensive reagent or catalyst, harsh reaction conditions, and toxic solvents.
In continuation of our studies on arylglyoxals chemistry (43–45), herein we wish to report the
first Willgerodt–Kindler reaction of arylglyoxal hydrates 1 with amines 2 and elemental sulfur in
water to afford α-ketothioamides 3.
2. Results and discussion
The Willgerodt–Kindler reaction in water was first studied using phenylglyoxal hydrate 1a and
piperidine 2a and elemental sulfur under different conditions and 1-phenyl-2-(piperidin-1-yl)-
2-thioxoethanone 3a was obtained in good yield (61%) when a mixture of 1a (0.5 mmol), 2a
(1 mmol) and elemental sulfur (1 mmol) in water was heated at 80◦C for 1 h (Scheme 1).
Scheme 1. Synthesis of 1-phenyl-2-(piperidin-1-yl)-2-thioxoethanone 3a.
The scope of the reaction was investigated using different arylglyoxal hydrates 1 and amines
2, which are summarized in Table 1. Reactions were carried out by heating of a mixture of 1
(0.5 mmol) with 2 (1 mmol) and sulfur (1 mmol) in 2 ml water at 80◦C for 0.6–1 h, and filtration
of the obtained solid followed by recrystallization and filtration in hot EtOH to remove unre-
acted sulfur or in situ generated ammonium polysulfide. As shown in Table 1, phenylglyoxal
and arylglyoxals with electron-withdrawing groups such as chloro and bromo worked as well as
substrates with electron-donating substituents such as methoxy group in the Willgerodt–Kindler
reaction with heterocyclic amines 2a–2c. Due to the low nucleophilicity and steric repulsion of
diethylamine 2d and benzylamine 2e, the Willgerodt–Kindler reaction did not occur, and instead
a non-identified mixture (Entries 4 and 5) was obtained. Also, the Willgerodt–Kindler reaction
of phenylglyoxal 1a with aniline 2f under similar conditions was investigated, in which corre-
sponding imine 4 was obtained without incorporation of sulfur in the reaction (Entry 6). In the
case of 4-nitrophenylglyoxal 1h, a polymeric material was produced, which can be attributed to
the reduction of nitro group to amine in the presence of elemental sulfur and then reaction with
carbonyl groups of other arylglyoxal molecules (Entry 20).
In a plausible mechanism for the Willgerodt–Kindler reaction (Scheme 2) of 1a with 2a and
elemental sulfur in water, the insoluble solid 1a in water rapidly formed a white suspension by
the addition of 2a, leading to the conclusion that rapid equilibria between 1a and iminium salts
5 were established. Nucleophilic addition of 2a to sulfur generated piperidinium sulfide 6 which
subsequently lost S7 to give intermediate 6. Intermediate 7 was then produced by nucleophilic
addition of 6 to iminium salt 5, which was converted into α-ketothioamide 3a by the elimination
of a molecule of piperidine (Scheme 2).

Journal of Sulfur Chemistry
3
Table 1. Willgerodt–Kindler reaction of arylglyoxal hydrates with amines in water.
Entry
ArCOCHO·H2O, 1
Amine, 2
Product, 3
Yield (%)a
1
61
1a
2a
2b
3a
2
50
3b
3c
3
4
5
70
–
2c
2d
2e
b
–
–
b
–
6
7
85
65
70
4(46)
2f
1b
2a
3d
8
9
2b
3e
3f
60
2c
(Continued)

4
B. Eftekhari-Sis et al.
Table 1. Continued
Entry
10
ArCOCHO·H2O, 1
Amine, 2
Product, 3
Yield (%)a
70
1c
2a
2b
3g
11
12
65
70
3h
3i
2c
13
14
75
70
1d
2a
3j
2c
3k
15
16
75
80
1e
1f
2a
3l
3m
3n
MeO
2c
17
75
2a
(Continued)

Journal of Sulfur Chemistry
5
Table 1. Continued
Entry
ArCOCHO·H2O, 1
Amine, 2
Product, 3
Yield (%)a
18
80
2c
3o
3p
19
20
80
1g
1h
2a
2a
c
–
Notes: aYields refer to isolated products.
bNon-identified mixture were obtained.
cA polymeric material was produced.
Scheme 2. Plausible mechanism for the Willgerodt–Kindler reaction of 1a with 2a and sulfur
in water.
Also, as shown in Scheme 3, the chemoselectivity of the Willgerodt–Kindler reaction of 1a
with 2a and sulfur in water at 80◦C was investigated by carrying out the reaction in the presence
of an equimolar amount of either benzaldehyde 8 or acetophenone 9, and after 1 h, only 3a was
isolated and 8 or 9 were recovered without any change.
3. Conclusion
In conclusion, we have reported a simple and efficient approach for the synthesis of α-
ketothioamides via the Willgerodt–Kindler reaction of arylglyoxal hydrates with secondary

6
B. Eftekhari-Sis et al.
Scheme 3. Chemoselectivity of the Willgerodt–Kindler reaction.
amines and elemental sulfur in water. Arylglyoxals with electron-donating and electron-
withdrawing groups worked equally well in the Willgerodt–Kindler reaction. Heterocyclic
secondary amines afforded the corresponding α-ketothioamides in good to high yields, while
reactions with secondary acyclic and primary amines produced a non-identified mixture.Also, the
reaction shows excellent chemoselectivity toward phenylglyoxal in preference to benzaldehyde
and acetophenone.
4. Experimental
Melting points were determined with an electrothermal 9100 apparatus. Fourier transform infrared
(FT-IR) spectra were recorded on a Unicam/Mattson 8700 spectrometer. 1H and 13C NMR spectra
were recorded on a Bruker 400 spectrometer in CDCl3. The chemicals used in this work were
purchased from Fluka and Mreck and were used without further purification.Arylglyoxal hydrates
were prepared by the oxidation of acetophenones using SeO2 in refluxing dioxane in the presence
of water as done in the Riley et al. (47) method.
4.1. General procedure for the Willgerodt–Kindler reaction
Arylglyoxal hydrate 1 (1 mmol) was added to a mixture of amine 2 (2 mmol) and elemental sulfur
(2 mmol) in 2 ml water and heated at 80◦C for 0.6–1 h.After completion of the reaction, monitored
byTLC(n-hexane/EtOAc:7/3), theobtainedsolidwasremovedbyfiltration.Theunreactedsulfur
was removed by adding 2 ml EtOH, heating and then hot filtration. By cooling, corresponding
α-ketothioamides were crystallized and separated by simple filtration. Further purification for
elemental analysis was carried out by recrystallization in n-hexane or EtOH. In the case of oily
products, column chromatography was used for purification. Compounds 3a, 3b, 3d, 3e and 3h
are known and were characterized using FT-IR, 1H NMR and 13C NMR spectra in comparison
with reported ones (39, 40). Unknown compounds were characterized using FT-IR, 1H NMR, 13
C
NMR and elemental analysis.
4.1.1. 1-Phenyl-2-(piperidin-1-yl)-2-thioxoethanone (3a) (39)
Yellow solid; m.p. 60–62◦C, FT-IR (KBr) (νmax cm−1): 3237, 2942 (C H), 1663 (C O),
−
=
=
=
−
−
1638 (C C), 1618, 1506 (C S), 1441 (CH2 bending), 1272 (C O), 1249 (C N), 1123
1
=
(C S). H NMR (400 MHz, CDCl3): 1.61–1.68 (2H, m, br, CH2), 1.77–1.86 (4H, m, CH2),
3.55–3.58 (2H, m, CH2–N), 4.27–4.3 (2H, m, CH2–N), 7.51 (2H, t, 3JHH = 7.6 Hz, CHAr), 7.63

Journal of Sulfur Chemistry
7
3
3
(1H, t, JHH = 7.6 Hz, CHAr), 8.01 (2H, d, JHH = 8.4 Hz, CHAr) ppm. 13C NMR (100 MHz,
=
=
CDCl3): 24.1, 25.4, 26.5, 48.1, 53.0, 128.9, 129.8, 133.4, 134.2, 188.0 (C O), 194.4 (C S) ppm.
4.1.2. 2-Morpholino-1-phenyl-2-thioxoethanone (3b) (39)
Yellow Solid; m.p. 114–116◦C, FT-IR (KBr) (νmax cm−1): 3110, 2970 (C H), 1664 (C O),
−
=
1
=
=
−
−
=
1595 (C C), 1500 (C S), 1443 (CH2 bending), 1267 (C O), 1233 (C N), 1111 (C S). H
NMR (400 MHz, CDCl3): 3.62–3.64 (2H, m, CH2–N), 3.71–3.73 (2H, m, CH2–N), 3.92–3.95
3
(2H, m, CH2–O), 4.34–4.37 (2H, m, CH2–O), 7.47 (2H, t, JHH = 7.6 Hz, CHAr), 7.57 (1H, t,
3JHH = 7.6 Hz, CHAr), 8.02 (2H, d, 3JHH = 8.4 Hz, CHAr) ppm. 13C NMR (100 MHz, CDCl3):
=
=
47.1, 51.9, 66.5, 66.8, 129.2, 130.1, 133.3, 134.5, 187.4 (C O), 195.7 (C S) ppm.
4.1.3. 1-Phenyl-2-(pyrrolidin-1-yl)-2-thioxoethanone (3c)
Yellow oil, FT-IR (KBr) (νmax cm−1): 3100, 2971 (C H), 1665 (C O), 1620 (C C), 1501 (C S),
−
=
=
=
1
−
=
1449 (CH2 bending), 1260 (C N), 1172 (C S). H NMR (400 MHz, CDCl3): 2.14–2.04 (4H,
3
m, CH2), 3.58–3.55 (2H, m, CH2–N), 3.99–3.96 (2H, m, CH2–N), 7.50 (2H, t, JHH = 7.6 Hz,
3
3
CHAr), 7.63 (1H, t, JHH = 7.2 Hz, CHAr), 8.01 (2H, d, JHH = 8.8 Hz, CHAr) ppm. 13C NMR
=
=
(100 MHz, CDCl3): 23.9, 26.1, 51.1, 51.3, 128.9, 130.1, 132.8, 134.2, 188.8 (C O), 192.8 (C S)
ppm. Anal. Calcd for C12H13NOS: C, 65.72; H, 5.97; N, 6.39%. Found: C, 65.64; H, 6.01; N,
6.87.
4.1.4. 1-(4-Chlorophenyl)-2-(piperidin-1-yl)-2-thioxoethanone (3d) (39)
Yellow solid; m.p. 108–110◦C, FT-IR (KBr) (νmax cm−1): 2940 (C H), 1665 (C O), 1586 (C C),
−
=
=
1
=
−
=
1506 (C S), 1445 (CH2 bending), 1223 (C N), 1011 (C S). H NMR (400 MHz, CDCl3): 1.58–
1.72 (2H, m, br., CH2), 1.80–1.86 (4H, m, CH2), 3.54–3.57 (2H, m, CH2–N), 4.25–4.28 (2H, m,
CH2–N), 7.65 (2H, d, 3JHH = 8.4 Hz, CHAr), 7.88 (2H, d, 3JHH = 8.4 Hz, CHAr) ppm.13C NMR
=
(100 MHz, CDCl3): 24.1, 25.4, 26.5, 48.1, 53.0, 128.9, 129.8, 133.4, 134.2, 188.0 (C O), 194.4
=
(C S) ppm.
4.1.5. 1-(4-Chlorophenyl)-2-morpholino-2-thioxoethanone (3e) (39)
Yellow solid; m.p. 130–132◦C, FT-IR (KBr) (νmax cm−1): 3100, 2990 (C H), 1655 (C O), 1617
−
=
1
=
=
−
−
=
(C C), 1568, 1498 (C S), 1437 (CH2 bending), 1274 (C O), 1235 (C N), 1113 (C S). H
NMR (400 MHz, CDCl3): 3.62–3.64 (2H, m, CH2–N), 3.73–3.75 (2H, m, CH2–N), 3.93–3.95
(2H, m, CH2–O), 4.34–4.37 (2H, m, CH2–O), 7.50 (2H, d, 3JHH = 8.4 Hz, CHAr), 7.97 (2H, d,
3JHH = 8.8 Hz, CHAr) ppm. 13C NMR (400 MHz, CDCl3): 47.2, 52.0, 66.4, 66.6, 129.4, 131.2,
=
=
131.7, 141.1, 186.5 (C O), 194.9 (C S) ppm.
4.1.6. 1-(4-Chlorophenyl)-2-(pyrrolidin-1-yl)-2-thioxoethanone (3f)
Brown yellow solid; m.p. 112–114◦C, FT-IR (KBr) (νmax cm−1): 2970 (C H), 1664 (C O),
−
=
=
=
−
=
−
1638 (C C), 1589, 1505 (C S), 1448 (CH2 bending), 1263 (C N), 1087 (C S), 620 (C Cl).
1H NMR (400 MHz, CDCl3): 2.06–2.20 (4H, m, CH2), 3.56–3.59 (2H, m, CH2–N), 4.00–3.96
(2H, m, CH2–N), 7.48 (2H, d, 3JHH = 8.8 Hz, CHAr), 7.98 (2H, d, 3JHH = 8.8 Hz, CHAr) ppm.
13
=
C NMR (100 MHz, CDCl3): 23.8, 26.1, 51.2, 51.3, 129.2, 131.4, 131.5, 140.8, 187.0 (C O),
=
192.0 (C S) ppm. Anal. Calcd for C12H12ClNOS: C, 56.80; H, 4.77; N, 5.52%. Found: C, 55.98;
H, 4.74; N, 5.03.

8
B. Eftekhari-Sis et al.
4.1.7. 1-(4-Bromophenyl)-2-(piperidin-1-yl)-2-thioxoethanone (3g)
Brown yellow solid; m.p. 119–121◦C, FT-IR (KBr) (νmax cm−1): 2932 (C H), 1663 (C O),
−
=
1
=
=
−
=
1583 (C C), 1505 (C S), 1445 (CH2 bending), 1223 (C N), 1010 (C S). H NMR (400 MHz,
CDCl3): 1.62–1.66 (2H, m, br, CH2), 1.76–1.88 (4H, m, br, CH2), 3.54–3.57 (2H, m, CH2–N),
3
3
4.25–4.28 (2H, m, CH2–N), 7.65 (2H, d, JHH = 8.4 Hz, CHAr), 7.88 (2H, d, JHH = 8.4 Hz,
CHAr) ppm. 13C NMR (100 MHz, CDCl3): 24.1, 25.4, 26.5, 48.2, 53.1, 129.2, 131.2, 131.9,
=
=
140.7, 186.5 (C O), 193.7 (C S) ppm. Anal. Calcd for C13H14BrNOS: C, 50.01; H, 4.52; N,
4.49%. Found: C, 50.30; H, 4.51; N, 4.59.
4.1.8. 1-(4-Bromophenyl)-2-morpholino-2-thioxoethanone (3h) (40)
Yellow solid; m.p. 115–117◦C, FT-IR (KBr) (νmax cm−1): 3200, 2990 (C H), 1636 (C O), 1621
−
=
1
=
=
−
−
=
(C C), 1584, 1503 (C S), 1435 (CH2 bending), 1271 (C O), 1231 (C N), 1112 (C S). H
NMR (400 MHz, CDCl3): 3.61–3.64 (2H, m, CH2–N), 3.72–3.75 (2H, m, CH2–N), 3.92–3.95
(2H, m, CH2–O), 4.34–4.37 (2H, m, CH2–O), 7.67 (2H, d, 3JHH = 8.4 Hz, CHAr), 7.89 (2H, d,
3JHH = 8.8 Hz, CHAr) ppm. 13C NMR (400 MHz, CDCl3): 47.2, 52.0, 66.4, 66.5, 129.4, 131.2,
=
=
132.3, 141.2, 188.1 (C O), 193.8 (C S) ppm.
4.1.9. 1-(4-Bromophenyl)-2-(pyrrolidin-1-yl)-2-thioxoethanone (3i)
Yellow solid; m.p. 102–104◦C, FT-IR (KBr) (νmax cm−1): 2990, 2923 (C H), 1638 (C O), 1613
−
=
1
=
=
−
=
(C C), 1498 (C S), 1453 (CH2 bending), 1260 (C N), 1080 (C S). H NMR (400 MHz,
CDCl3): 2.07–2.16 (4H, m, CH2), 3.55–3.58 (2H, m, CH2–N), 3.96–3.99 (2H, m, CH2–N),
7.63–7.66 (2H, m, CHAr), 7.88–7.93 (2H, m, CHAr) ppm. 13C NMR (100 MHz, CDCl3): 23.8,
=
=
26.1, 51.2, 51.3, 129.7, 131.6, 131.8, 132.2, 187.5 (C O), 191.9 (C S) ppm. Anal. Calcd for
C12H12BrNOS: C, 48.33; H, 4.06; N, 4.70%. Found: C, 47.88; H, 4.09; N, 5.01.
4.1.10. 1-(4-Biphenyl)-2-(piperidin-1-yl)-2-thioxoethanone (3j)
Yellow solid; m.p. 104–106◦C, FT-IR (KBr) (νmax cm−1): 2936 (C H), 1659 (C O), 1601 (C C),
−
=
=
1
=
−
=
1503 (C S), 1443 (CH2 bending), 1226 (C N), 1131 (C S). H NMR (400 MHz, CDCl3): 1.65–
1.74 (2H, m, br, CH2), 1.82–1.88 (4H, m, CH2), 3.60–3.62 (2H, m, CH2–N), 4.29–4.32 (2H, m,
3
3
CH2–N), 7.44 (1H, t, JHH = 7.2 Hz, CHph), 7.51 (2H, t, JHH = 7.4 Hz, CHph), 7.50 (2H, d,
3
3
3JHH = 7.4 Hz, CHph), 7.73 (2H, d, JHH = 8.4 Hz, CHAr), 8.05 (2H, d, JHH = 8.4 Hz, CHAr)
ppm. 13C NMR (100 MHz, CDCl3): 24.1, 25.4, 26.5, 48.2, 53.1, 127.4, 127.5, 128.5, 129.0, 130.4,
=
=
132.2, 139.7, 147.0, 187.7 (C O), 194.5 (C S) ppm. Anal. Calcd for C19H19NOS: C, 73.75; H,
6.19; N, 4.53%. Found: C, 73.25; H, 6.21; N, 4.88.
4.1.11. 1-(4-Biphenyl)-2-(pyrrolidin-1-yl)-2-thioxoethanone (3k)
Orangeyellowsolid;m.p. 120–122◦C, FT-IR(KBr)(νmax cm−1):3237, 2974(C H), 1663(C O),
−
=
1
=
=
−
=
1618 (C C), 1559, 1503 (C S), 1449 (CH2 bending), 1266 (C N), 1180 (C S). H NMR
(400 MHz, CDCl3): 2.09–2.16 (4H, m, CH2), 3.61–3.64 (2H, m, CH2–N), 3.99–4.03 (2H, m,
CH2–N), 7.45–7.47 (1H, m, CHph), 7.49–7.53 (2H, m, CHph), 7.64–7.66 (2H, m, CHph), 7.72
3
3
(2H, d, JHH = 8.4 Hz, CHAr), 8.10 (2H, d, JHH = 8.4 Hz, CHAr) ppm. 13C NMR (100 MHz,
CDCl3): 23.9, 26.1, 51.1, 51.3, 127.4, 127.5, 128.5, 129.0, 130.7, 131.6, 139.7, 147.0, 188.5
=
=
(C O), 192.8 (C S) ppm. Anal. Calcd for C18H17NOS: C, 73.19; H, 5.80; N, 4.74%. Found: C,
73.77; H, 5.83; N, 4.65.

Journal of Sulfur Chemistry
9
4.1.12. 1-(4-Methoxyphenyl)-2-(piperidin-1-yl)-2-thioxoethanone (3l)
Yellow solid; m.p. 83–85◦C, FT-IR (KBr) (νmax cm−1): 2939 (C H), 1653 (C O), 1593 (C C),
−
=
=
1
=
−
−
=
1511, 1456 (C S), 1321 (CH2 bending), 1272 (C O), 1237 (C N), 1129 (C S). H NMR
(400 MHz, CDCl3): 1.60–1.68 (2H, m, br, CH2), 1.79–1.85 (4H, m, CH2), 3.52–3.59 (2H, m,
3
br, CH2–N), 4.24–4.31 (2H, m, br, CH2–N), 6.97 (2H, d, JHH = 8.8 Hz, CHAr), 7.98 (2H, d,
3JHH = 8.8 Hz, CHAr) ppm. 13C NMR (100 MHz, CDCl3): 24.1, 25.4, 26.5, 48.1, 53.0, 55.6,
=
=
114.2, 126.3, 132.3, 164.4, 187.4 (C O), 194.9 (C S) ppm. Anal. Calcd for C14H17NO2S: C,
63.85; H, 6.51; N, 5.32%. Found: C, 63.83; H, 6.51; N, 5.23.
4.1.13. 1-(4-Methoxyphenyl)-2-(pyrrolidin-1-yl)-2-thioxoethanone (3m)
Brown yellow solid; m.p. 112–114◦C, FT-IR (KBr) (νmax cm−1): 2939 (C H), 1653 (C O),
−
=
=
=
−
−
=
1593 (C C), 1511, 1456 (C S), 1321 (CH2 bending), 1272 (C O), 1237 (C N), 1129 (C S).
1H NMR (400 MHz, CDCl3): 2.05–2.13 (4H, m, CH2), 3.55–3.59 (2H, m, CH2–N), 3.90 (3H,
s, OCH3), 3.96–4.00 (2H, m, CH2–N), 6.97 (2H, d, 3JHH = 9.2 Hz, CHAr), 8.00 (2H, d, 3JHH
=
8.8 Hz, CHAr) ppm. 13C NMR (100 MHz, CDCl3): 23.9, 26.1, 51.1, 51.2, 55.6, 114.2, 125.7,
=
=
132.6, 164.5, 188.1 (C O), 193.2 (C S) ppm. Anal. Calcd for C13H15NO2S: C, 62.62; H, 6.06;
N, 5.62%. Found: C, 62.60; H, 6.06; N, 5.77.
4.1.14. 1-(3-Methoxyphenyl)-2-(piperidin-1-yl)-2-thioxoethanone (3n)
Yellow oil, FT-IR (KBr) (νmax cm−1): 2940 (C H), 1665 (C O), 1584 (C C), 1505 (C S),
−
=
=
=
1
−
−
=
1447 (CH2 bending), 1282 (C O), 1250 (C N), 1101 (C S). H NMR (400 MHz, CDCl3):
1.61–1.68 (2H, m, br, CH2), 1.78–1.84 (4H, m, CH2), 3.54–3.56 (2H, m, CH2–N), 3.87 (3H,
3
s, OCH3), 4.24–4.27 (2H, m, CH2–N), 7.14–7.17 (1H, m, CHAr), 7.39 (1H, t, JHH = 8.0 Hz,
CHAr), 7.52–7.57 (2H, m, CHAr) ppm. 13C NMR (100 MHz, CDCl3): 24.1, 25.4, 26.4, 48.1, 53.0,
=
=
55.6, 113.3, 120.9, 122.7, 129.9, 134.8, 160.0, 187.8 (C O), 194.3 (C S) ppm. Anal. Calcd for
C14H17NO2S: C, 63.85; H, 6.51; N, 5.32%. Found: C, 63.76; H, 6.50; N, 5.18.
4.1.15. 1-(3-Methoxyphenyl)-2-(pyrrolidin-1-yl)-2-thioxoethanone (3o)
Yellow solid; m.p. 111–113◦C, FT-IR (KBr) (νmax cm−1): 3100, 2990 (C H), 1644 (C O), 1615
−
=
1
=
=
−
−
=
(C C), 1515 (C S), 1274 (C O), 1245 (C N), 1035 (C S). H NMR (400 MHz, CDCl3):
2.06–2.13 (4H, m, CH2), 3.56–3.59 (2H, m, CH2–N), 3.88 (3H, s, OCH3), 3.96–3.97 (2H, m,
CH2–N), 7.16–7.18 (1H, m, CHAr), 7.4 (1H, t, 3JHH = 8.4 Hz, CHAr), 7.52–7.58 (2H, m, CHAr)
ppm. 13C NMR (100 MHz, CDCl3): 23.9, 26.1, 51.1, 51.3, 55.6, 113.7, 121.0, 123.1, 129.9,
=
=
134.2, 160.0, 188.6 (C O), 192.7 (C S) ppm. Anal. Calcd for C13H15NO2S: C, 62.62; H, 6.06;
N, 5.62%. Found: C, 62.80; H, 6.18; N, 6.04.
4.1.16. 1-(3,4-Dimethoxyphenyl)-2-(piperidin-1-yl)-2-thioxoethanone (3p)
Brown yellow solid; m.p. 148–150◦C, FT-IR (KBr) (νmax cm−1): 2993, 2947 (C H), 1652 (C O),
−
=
=
=
−
−
=
1618 (C C), 1586, 1507 (C S), 1444, (CH2 bending), 1273 (C O), 1246 (C N), 1129 (C S).
1H NMR (400 MHz, CDCl3): 1.60–1.72 (2H, m, br, CH2), 1.80–1.85 (4H, m, CH2), 3.53–3.61
(2H, m, br, CH2–N), 3.96 (3H, s, OCH3), 3.98 (3H, s, OCH3), 4.24–4.32 (2H, m, br, CH2–
3
3
N), 6.91 (1H, d, JHH = 8.4 Hz, CHAr), 7.78 (1H, dd, JHH = 2.0, 8.4 Hz, CHAr), 7.63 (1H, d,
3JHH = 2.0 Hz, CHAr) ppm. 13C NMR (100 MHz, CDCl3): 24.1, 25.4, 26.5, 48.2, 53.0, 56.1,

10 B. Eftekhari-Sis et al.
=
=
56.2, 110.3, 111.0, 125.5, 126.4, 149.4, 154.2, 187.5 (C O), 194.8 (C S) ppm. Anal. Calcd for
C15H19NO3S: C, 61.41; H, 6.53; N, 4.77%. Found: C, 61.39; H, 6.52; N, 4.53.
Acknowledgements
This work was partially supported by the research council of the University of Maragheh. B.E.S. gratefully acknowledges
Mr Biglari (IASBS) for taking NMR spectra and Dr M. Rimaz (PNU) for preparing methoxy phenylglyoxals.
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