A study of the Willgerodt-Kindler reaction to obtain thioamides and α-ketothioamides under solvent-less conditions

Article abstract of DOI:10.1139/v2012-030

In this paper, the results obtained in the synthesis of thioamides and α-ketothioamides by a modification of the Willgerodt-Kindler reaction, under solvent-free and noncatalyst conditions using IR energy as a source of activation, are presented. The use of IR energy in these reactions has been shown to lead to a mixture of thioamide and α-ketothioamide as the main products in most cases, with the latter predominating. The yields of α-ketothioamides from most of these reactions are better than those reported previously. To the best of our knowledge, this is the first time that IR energy has been applied to promote the Willgerodt-Kindler reaction.

Full text of DOI:10.1139/v2012-030

567
A study of the Willgerodt–Kindler reaction to
obtain thioamides and α-ketothioamides under
solvent-less conditions
José Ernesto Valdez-Rojas, Hulme Ríos-Guerra, Alma Leticia Ramírez-Sánchez,
Guadalupe García-González, Cecilio Álvarez-Toledano,
José Guadalupe López-Cortés, Rubén A. Toscano, and
José Guillermo Penieres-Carrillo
Abstract: In this paper, the results obtained in the synthesis of thioamides and a-ketothioamides by a modification of the
Willgerodt–Kindler reaction, under solvent-free and noncatalyst conditions using IR energy as a source of activation, are
presented. The use of IR energy in these reactions has been shown to lead to a mixture of thioamide and a-ketothioamide
as the main products in most cases, with the latter predominating. The yields of a-ketothioamides from most of these reac-
tions are better than those reported previously. To the best of our knowledge, this is the first time that IR energy has been
applied to promote the Willgerodt–Kindler reaction.
Key words: Willgerodt–Kindler modification, a-ketothioamides, solvent-less conditions, IR energy, noncatalyst.
Résumé : Dans ce travail, on rapporte les résultats obtenus lors de la synthèse de thioamides et de a-cétothioamides, par le
biais d’une modification de la réaction de Willgerodt–Kindler dans des conditions qui n’impliquent aucun solvant et aucun
catalyseur et qui utilisent l’énergie infrarouge comme source d’activation. On a démontré que l’utilisation de l’infrarouge
dans ces réactions conduit, dans la plupart des cas, à des mélanges contenant comme produits principaux un thioamide et
un a-cétothioamide et que ce dernier est prédominant. Les rendements en a-cétothioamides, pour la plupart des réactions,
sont meilleurs que ceux rapportés antérieurement. Au meilleur de nos connaissances, c’est la première fois que l’énergie de
l’infrarouge a été utilisée pour la promotion de la réaction de Willgerodt–Kindler.
Mots‐clés : modification de la réaction de Willgerodt-Kindler, a-cétothioamides, conditions expérimentales sans solvant,
énergie infrarouge, sans catalyseur.
[Traduit par la Rédaction]
pounds,9 but this method has some limitations, i.e., long re-
Introduction
action times are required and low yields are achieved. This
reaction is characterized by the use of alkyl aryl ketones or
aldehydes, elemental sulfur, and amines, with morpholine
being the most commonly used amine. When ketones are
used in this methodology, the carbonyl group is reduced to a
methylene group and the terminal methyl group is oxidized
to a thiocarbonyl group (I, Scheme 1).
Previous studies using thermal energy for the activation of
reactions have yielded some unexpected results, with the
most common problem being the failure to reduce the car-
bonyl group in the alkyl aryl ketone used, leading to the for-
mation of the a-ketothioamide II as a reaction byproduct.
Dauben and Rogan,10 Harris et al.11 Harrowven and Lucas,12
and Liu et al.13 encountered this problem and generated II in
yields of 3%–20% when using reaction times of 8–24 h. In
Thioamides are among the most extensively studied chal-
cogen-containing compounds. They are known to demon-
strate biological activity,1 are used as synthetic intermediates
in organic chemistry,2 have been found in natural products,
and have many applications in materials science and indus-
trial processes.3 They are also employed as insecticides4 be-
cause they are well tolerated by plants and have low toxicity
in higher animals, and they are used in medical applications,
for example, in tuberculosis treatment,5 as painkillers,6 and as
antioxidants.7
Currently, it is possible to find several methods for the
synthesis of thioamides, most of which employ Lawesson’s
reagent.8 However, there are also publications concerning the
Willgerodt–Kindler method for the generation of these com-
Received 31 October 2011. Accepted 27 March 2012. Published at www.nrcresearchpress.com/cjc on 12 June 2012.
J.E. Valdez-Rojas, H. Ríos-Guerra, A.L. Ramírez-Sánchez, G. García-González, and J.G. Penieres-Carrillo. Facultad de Estudios
Superiores Cuautitlán-Universidad Nacional Autónoma de México, Sección de Química Orgánica, FESC, Campo 1, Avenida 1 de mayo s/n,
Colonia Santa María Guadalupe Las Torres, Cuautitlán Izcalli, C. P. 54740, México.
C. Álvarez-Toledano, J.G. López-Cortés, and R.A. Toscano. Instituto de Química-Universidad Nacional Autónoma de México, Circuito
Exterior, Ciudad Universitaria, Coyoacán, México D.F, C.P. 04510, México.
Corresponding author: José Guillermo Penieres-Carrillo (e-mail: penieres@unam.mx).
Can. J. Chem. 90: 567–573 (2012)
doi:10.1139/V2012-030
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568
Can. J. Chem. Vol. 90, 2012
Scheme 1. General reaction conditions for the synthesis of thio-
amides. Dauben and Rogan:10 Acetophenone (2.0 g, 12.3 mmol),
elemental sulfur (0.40 g, 12.3 mmol), morpholine (1.08 g,
12.3 mmol); R1 = Me, R2 = Me, R3 = H, R4 = Me; yield (II) =
20%; 8 h. Harris et al.:11 Acetophenone (5.0 g, 20.4 mmol), ele-
mental sulfur (1.0 g, 31.25 mmol), morpholine (2.82 g, 32.4 mmol);
R1 = OC6H5, R2 = H, R3 = Cl, R4 = H; yield (I) = 46%, II not
isolated; 20 h. Harrowven and Lucas:12 Acetophenone (23.3 g,
142 mmol), elemental sulfur (6.8 g, 213 mmol), morpholine (18.5 g,
213 mmol); R1 = OMe, R2 = Me, R3 = H, R4 = H; yield (I) =
57%, yield (II) = 10%; 24 h. Liu et al.:13 Acetophenone (12.2 g,
100 mmol), elemental sulfur (4.8 g, 150 mmol), morpholine (11.3 g,
130 mmol); R1 = R2 = R3 = R4 = H; yield (I) = 66%, yield (II) =
3%; 20 h.
ation with IR energy at a wavelength of 1100 nm (near-IR)
for 1 h at 100 °C29 were optimal conditions for the genera-
tion of the corresponding a-ketothioamide. In this way, the
desired product was obtained exclusively in 56% yield.
This result encouraged us to study the reaction using other
acetophenones and amines, to establish this method as a gen-
eral route to synthesize a-ketothioamides 3 (Scheme 2).
We found that, under these conditions, this reaction en-
sured that the a-ketothioamides 3a–3h (Table 1) were gener-
ated as the main products in most cases, and the yields were
higher than those obtained (3%–20%) by other synthetic
methods previously reported in the literature. The Willgerodt–
Kindler products 4a–4h were also detected in yields ranging
from 0%–42% as a second product. Thus, with the method-
ology employed in this work, the outcome of the Willgerodt–
Kindler reaction can be regarded as unclassical.
The products 3a–3h were obtained in yields close to or
higher than 50%, although when 2-methylpiperidine was
used as the amine, a yield of only 20% was obtained, which
may be attributed to steric factors. In entries 1–5 of Table 1,
the products were synthesized from unsubstituted acetophe-
none, and the amine used was either morpholine, piperidine,
or methylated regioisomers of the latter.
When the reaction was carried out with p-chloroacetophenone,
a crystalline product was formed, and a single crystal could
be used for X-ray diffraction study30 (Fig. 1).
It is important to mention that the low yields of 3 shown
in entries 7 and 8 in Table 1 were due to a competitive SNAr
reaction resulting in the formation of p-morpholino- or p-(1-
piperidinyl)acetophenone31 in yields of 20% and 19%, respec-
tively, along with the corresponding thioamides from the
Willgerodt–Kindler reaction, compounds 4g and 4h
(Scheme 2; Table 1).
We also studied the reactions leading to the synthesis of
3a–3h at room temperature, to determine the influence of
temperature and energy source on their outcomes. The reac-
tions were monitored for 48 h by TLC, and the conversion
percentages were measured by gas chromatography coupled
with mass spectrometry (Table 2). More than 50% of the ace-
tophenone remained unreacted in some cases (Table 2, en-
tries 7 and 8), and the behavior of these reactions was
similar when IR energy was used. These results clearly dem-
onstrated that the reactions proceeded better when activated
with IR energy than when conducted at room temperature,
and established the importance of IR energy in the synthesis
of a-ketothioamides 3. The formation of 4a–4h was detected
and the results are summarized in Table 2.
To compare the use of thermal conditions and IR energy
for the synthesis of a-ketothioamides, we performed the reac-
tions to obtain 3a and 3b under reflux conditions. After 5 h
of reaction, with hourly monitoring by TLC, no formation of
the corresponding a-ketothioamides could be detected. This
behavior is consistent with the reported results by Liu et
al.13 for the reaction employing acetophenone, elemental sul-
fur, and morpholine at reflux temperature (83–85 °C),
whereby 3 was obtained in just 3% yield after 20 h of reac-
tion. In contrast, in the present study, the same compound
(Table 1, entry 1) was obtained in 56% yield in a reaction
time of 1 h. Moreover, Carmack et al.32 reported similar reac-
tion conditions to those used in the present paper (100 °C,
elemental sulfur, morpholine, and solvent-less conditions) for
these reports, the reactions were performed at reflux, in the
absence of solvent, employing acetophenones, elemental sul-
fur, and morpholine. However, the methodology developed in
these studies cannot be considered to be a general synthetic
route to a-ketothioamides II, because this unexpected prod-
uct of the Willgerodt–Kindler reaction was only generated in
isolated cases.
Other published routes to a-ketothioamides have employed
a-chloroketones,14 a-oxonitryl,15 thioacetomorpholides,16 pi-
nacolone (3,3-dimethyl-2-butanone),17 a-chlorosulfonyl and
trisulfane intermediates,18 or N,N-(dialkyl)aroylmethyl-
amines.19 However, like the Willgerodt–Kindler reaction,
these methodologies are not general for the synthesis of a-
ketothioamides. The reaction conditions employed are also
dangerous or require expensive reagents and long reaction
times. In general, thermal energy is used as the activation
source for the Willgerodt–Kindler reaction. The use of alter-
native energy sources such as ultrasound20 and micro-
waves21 has recently been explored, and microwave
activation has attracted particular attention. To the best of
our knowledge, however, the use of IR energy as an activa-
tion source for the Willgerodt–Kindler reaction has not yet
been reported. IR energy has been demonstrated to be use-
ful in organic synthesis,22 and has been used in the synthe-
sis of 1,3,5-trioxanes from aldehydes,23 in the Biginelli24
and Knoevenagel25 reactions, and for the synthesis of diin-
dolylmethanes26 and 3,4-dihydro-2(1H)-pyridones.27 When
investigating the synthesis of 3-caprolactam from cyclohexa-
none and hydroxylamine using bentonic clay under solvent-
less conditions, we explored the use of several energy sour-
ces for activation of the reaction and found that IR energy
performed better than thermal, microwave, or ultrasound en-
ergies.28
Results and discussion
We set out to explore the use of IR energy for the activa-
tion of the Willgerodt–Kindler reaction, employing acetophe-
none, elemental sulfur, and morpholine. After extensive
experimentation, we found that a stoichiometric ratio for the
starting materials of 1:1:1, solvent-less conditions, and irradi-
Published by NRC Research Press

Valdez-Rojas et al.
569
Table 1. Obtained results from the Willgerodt–Kindler reaction employing IR energy.
Time
(min)
60
Entry a-Ketothioamide
1
Yield(%)a
56; 3;13 58;b,14 94c,16
Willgerodt–Kindler product
Yield (%)a
Not formed; 50–8121a
2
3
4
50; 22;b,14 1119
20; 2619
67
39
60
Not formed
Not formed
150
60
5
6
48
54
Trace
60
30
Not formed
7
19; 83c,16
42; 40–5521a
60
60
8
12; 1019
11
aPurified product.
bFrom the linear synthesis (three steps); yield is for the last step.
cFrom the linear synthesis (two steps); yield is for the last step.
the reaction of linear and cyclic aliphatic ketones, using ther-
mal energy, and obtained only the Willgerodt–Kindler prod-
uct and carbonyl group isomerization products. Considering
all of these results, it is proposed that IR energy is responsi-
ble for the synthesis of 3 as the principal product, and not the
thermal heating that comes from the lamp employed in this
work (see the Supplementary data).
The use of IR energy gives very efficient heat transfer similar
Published by NRC Research Press

570
Can. J. Chem. Vol. 90, 2012
Scheme 2. Synthesis of thioamides from acetophenones, elemental sulfur, and heterocyclic amines.
1
Fig. 1. ORTEP for 1-(4-chlorophenyl)-2-piperidin-1-yl)-2-thioxo-
ethanone (3h).
commercial presentation, H and 13C NMR spectra were re-
corded by use of CDCl3 or acetone-d6 in Varian Mercury
200 and 300 MHz instruments, chemical shifts were reported
in ppm from TMS with the solvent resonance as the internal
standard, and coupling constants (J) are given in hertz, where
s was assigned to single, d for doublet, t for triplet, m for
multiple, and br for broad signals. The GC–MS analyses
were conducted with gas chromatograph model 6850 and
mass spectrometer 5975C by Agilent Technologies, employ-
ing a J&W HP-5MS capillary column. GC conditions: capil-
lary column (30 m × 0.25 mm i.d., 0.25 µm film), helium as
carrier gas at a constant flow velocity of 35 cm/s, and injec-
tor temperature 250 °C. MS data were reported as m/z (rela-
tive intensity). HRMS were recorded in an MStation JMS-
700 JEOL at 70 eV. Melting points were obtained on a
Fisher-Johns apparatus and are uncorrected. Analytical TLC
was performed using Kieselgel 60 F254 silica gel plates
(Merck, Darmstadt, Germany). A Buchi pump controller C-
610 and a Buchi pump module C-601 were employed for
flash chromatography. Elemental analyses were carried out
with an Elementar Vario EL III element analyser.
to that provided by microwave irradiation because both are
electromagnetic waves and the behavior is comparable. The
main effect produced by IR energy is thus an overheating in
the reaction mixture that favors the formation of 3. Mecha-
nistically, we are in agreement with the reaction mechanism
proposed by Darabi et al.33
IR equipment
The equipment used for irradiation with IR energy was
created by employing an empty cylindrical metal vessel in
which an Osram lamp (bulb model Thera-Therm, 250 W,
125 V) was inserted. This lamp is special short-wave IR
lamp (IR-A) for use in body care and wellness applications,
with a maximum radiation at a wavelength of about
1100 nm. The lamp instantly emits a full thermal output as
soon as it is switched on. For controlling the temperature, a
Digi-Sense variable-time power controller was used. This
time controller turned the output load on and off and then re-
peated the cycle.
Conclusion
In summary, we have described a new methodology for the
synthesis of a-ketothioamides as the principal products, em-
ploying a multicomponent reaction activated by IR energy
under solvent-less conditions. As far as we are aware, this is
the first report of the use of IR energy for activation of the
Willgerodt–Kindler reaction. We have established the utility
of this method for the generation of a-ketothioamides, a reac-
tion that could not previously be reliably accomplished by the
Willgerodt–Kindler protocol when thermal energy was used.
In all cases reported in this study, the a-ketothioamides were
produced in yields ranging from moderate to good, depending
on the substituents on the acetophenone aromatic ring.
This new methodology can be considered as a useful addi-
tion to the synthetic organic chemistry tool kit, as, to the best
of our knowledge, no method has hitherto been reported to
give a-ketothioamides in a one-pot reaction in yields better
than those reported here.
Typical procedure for the Willgerodt–Kindler reaction
employing IR energy
For the synthesis of 3a, the following were placed in a
tube: acetophenone 1a (100 mg, 0.83 mmol), elemental sul-
fur (27 mg, 0.83 mmol), and amine 2a (73 mg, 0.83 mmol).
This tube was then sealed and placed inside of the IR equip-
ment at 3–5 cm above the IR lamp. The reaction mixture was
irradiated at a wavelength of 1100 nm with IR energy at
100 °C for the appropriate time (30–150 min according to
Table 1) and monitored using TLC. The products obtained
as brown dark oils were purified using preparative plates or
flash chromatography with silica gel as a stationary phase
and a mixture of hexane – ethyl acetate as a mobile phase;
Experimental section
General
All reagents were from Sigma-Aldrich and used from its
Published by NRC Research Press

Valdez-Rojas et al.
571
Table 2. Conversion percentages using acetophenones, elemental sulfur, and heterocyclic amines at room
temperature.
Entry
Compound
Conversion (%)a
Compound
Conversion (%)a
Acetophenone (%)b
1
2
3
4
5
6
7
8
3a
3b
3c
3d
3e
3f
19
12
10
43
36
30
9
4a
4b
4c
4d
4e
4f
32
14
3
4
39
33
18
14
18
37
56
55
13
Not formed
12
10
3g
3h
4g
4h
9
aPercentage of conversion was measured by GC–MS.
bUnreacted raw material.
recrystallization processes were not necessary and pure prod-
ucts were characterized by 1H and 13C NMR and mass
spectrometry. Syntheses of 3b–3h were carried out with the
same procedure. Products 4a–4h were isolated and charac-
terized from the mixture of the reactions for the synthesis
of 3a–3h.
Hex/AcOEt, eluted twice): 0.22. IR (KBr, cm–1): 2928, 2860,
1
1737, 1667. H NMR (300 MHz, CDCl3, Me4Si) d : 8.01–
Η
7.94 (1H, m), 7.60–7.57 (2H, m), 7.51–7.46 (2H, m), 5.43–
5.39 (1H, m), 4.09 (2H, m), 3.64–3.57 (2H, m), 1.99 (2H,
m), 1.75 (2H, br), 1.25 (3H, s). 13C NMR (75 MHz, CDCl3)
dC: 194.3 (C=S), 187.5 (C=O), 134.0, 133.4, 129.6, 128.7,
56.3, 49.7, 47.5, 41.9, 30.6, 29.6, 25.9, 25.3, 18.5, 18.3,
16.4, 14.7. MS (EI) m/z: 247 (M+•, 64.37%), 142 (75), 98
(62.5), 18 (100). HRMS-EI calcd for C14H17ONS: 247.1031;
found: 247.1033.
Typical procedure for the Willgerodt–Kindler reaction at
room temperature
For the formation of 3a, elemental sulfur (184 mg,
5.7 mmol) was added to 500 mg (5.7 mmol) of amine 2a,
the reaction mixture was stirred for 2 h until the sulfur was
completely dissolved in the amine, and then acetophenone
1a (690 mg, 5.7 mmol) was added to the amine–sulfur mix-
ture and stirred at room temperature for 48 h. The reaction
was monitored by TLC and the conversion rates were deter-
mined by GC–MS. Compounds 3b–3h were obtained, replac-
ing the corresponding acetophenones 1a–1c and amines 2a–
2e following the typical procedure for 3a.
2-(3-Methylpiperidin-1-yl)-1-phenyl-2-thioxoethanone (3d)
Yield: 138 mg (67%); yellow solid, mp 45 °C. Rf (90%
Hex/AcOEt, eluted twice): 0.22. 1H NMR (300 MHz,
CDCl3, Me4Si) dΗ: 7.99–7.96 (1H, m), 7.62–7.57 (2H, m),
7.50–7.45 (2H, m), 5.33–5.21 (1H, m), 3.75–3.63 (2H, m),
3.28–3.07 (2H, m), 1.94–1.90 (2H, br), 1.82–1.68 (2H, br),
0.82–0.79 (3H, m). 13C NMR (75 MHz, CDCl3) dC: 194.4
(C=S), 187.8 (C=O), 134.0, 133.3, 129.7, 128.7, 58.9, 53.9,
52.4, 47.5, 32.5, 32.1, 31.2, 25.6, 24.4, 18.9, 18.5. HRMS-EI
calcd for C14H17ONS: 247.1031; found: 247.1030.
2-Morpholino-1-phenyl-2-thioxoethanone (3a)13,14,16
Yield: 109 mg (56%); pale yellow solid, mp 107–109 °C.
Rf (70% Hex/AcOEt): 0.42. 1H NMR (200 MHz, CDCl3,
Me4Si) dΗ: 8.01–7.97 (2H, m), 7.34–7.31 (3H, m), 4.37–
4.33 (1H, t, J = 9.8 Hz), 3.76–3.71 (1H, t, J = 9.8 Hz),
3.65–3.60 (1H, t, J = 9.6 Hz), 3.40–3.35 (1H, t, J =
9.6 Hz). 13C NMR (50 MHz, CDCl3) dC: 199.9 (C=S),
187.8 (C=O), 135.7, 128.9, 127.7, 127.1, 66.3, 50.7, 50.5,
50.1. MS (EI) m/z: 235 (M+•, 15%), 221 (100), 130 (35),
105 (5). HRMS-EI calcd for C12H13O2NS: 235.0667; found:
235.0655.
2-(4-Methylpiperidin-1-yl)-1-phenyl-2-thioxoethanone (3e)
Yield: 99 mg (48%); yellow solid, mp 53–55 °C. Rf (90%
Hex/AcOEt, eluted twice): 0.22. IR (KBr, cm–1): 2928, 2860,
1
1737, 1667. H NMR (300 MHz, CDCl3, Me4Si) dΗ: 7.98–
7.94 (1H, m), 7.60–7.54 (2H, m), 7.49–7.43 (2H, m), 5.41–
5.33 (1H, m), 3.78–3.70 (2H, m), 3.31–3.22 (2H, m), 1.96
(2H, m), 1.92–1.61 (2H, br), 1.22 (3H, s). 13C NMR
(75 MHz, CDCl3) dC: 194.4 (C=S), 187.9 (C=O), 134.0,
133.3, 129.7, 128.7, 52.0, 47.3, 34.2, 33.2, 30.7, 21.1. MS
(EI) m/z: 247 (M+•, 64.37%), 142 (75), 98 (62.5), 18 (100).
HRMS-EI calcd for C14H17ONS: 247.1031; found: 247.1032.
1-Phenyl-2-(piperidin-1-yl)-2-thioxoethanone (3b)14,19
Yield: 97 mg (50%); pale yellow solid, mp 53–55 °C. Rf
(90% Hex/AcOEt, eluted twice): 0.48. IR (KBr, cm–1): 2944,
1
2862, 1666, 1590. H NMR (300 MHz, CDCl3, Me4Si) dΗ:
1-(4-Nitrophenyl)-2-(piperidin-1-yl)-2-thioxoethanone (3f)
Yield: 91 mg (54%); yellow solid, mp 123–125 °C. Rf
(66% Hex/acetone): 0.46. 1H NMR (300 MHz, CDCl3,
7.99–7.96 (1H, m), 7.62–7.56 (2H, m), 7.50–7.44 (2H, m),
4.25–4.22 (2H, m), 3.54–3.50 (2H, m), 2.16 (2H, s), 1.82–
1.73 (2H, br), 1.62–1.60 (2H, br). 13C NMR (75 MHz,
CDCl3) dC: 194.2 (C=S), 187.9 (C=O), 134.1, 133.2, 129.6,
128.7, 52.9, 48.0, 26.3, 25.2, 23.9. MS (EI) m/z: 233 (M+•,
78.1%), 128 (100), 84 (53.1). HRMS-EI calcd for
C17H22O2N2S: 233.0874; found: 233.0873.
Me4Si) d : 7.77–7.74 (2H, m), 6.62–6.59 (2H, m), 4.43 (2H,
Η
m), 4.23 (2H, m), 3.53 (2H, m), 1.77 (2H, br), 1.74 (2H, br).
13C NMR (75 MHz, CDCl3) dC: 195.5 (C=S), 187.7 (C=O),
152.6, 132.5, 122.8, 113.9, 53.0, 48.2, 26.5, 25.4, 24.1. MS
(EI) m/z: 278 (M+•, 48%), 150 (6), 128 (100), 84 (96). Anal.
calcd for C13H14N2O3S (278.3): C 56.10, H 5.07, N 10.06;
found: C 60.49, H 6.19, N 10.23.
2-(2-Methylpiperidin-1-yl)-1-phenyl-2-thioxoethanone (3c)19
Yield: 42 mg (20%); yellow solid,. mp 65–68 °C. Rf (90%
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572
Can. J. Chem. Vol. 90, 2012
1-(4-Chlorophenyl)-2-morpholino-2-thioxoethanone (3g)16
Yield: 33 mg (19%); yellow solid, mp 150–152 °C. Rf
(73% Hex/AcOEt): 0.25. 1H NMR (300 MHz, CDCl3,
Acknowledgments
The authors want to thank to Mr. L.B. Hernández Portilla
and Dr. C.M. Flores Ortiz for GC–MS experiments done at
Unidad de Biotecnología y Prototipos Facultad de Estudios
Superiores (UBIPRO FES) - Iztacala Universidad Nacional
Autónoma de México (UNAM) and Programa de Apoyo a
Proyectos de Investigación e Innovación Tecnológica (PAPIT)
for the project support (IN207208). J.E.V.-R. would like to
thank CONACYT for support given through Ph.D. grant
No. 226777.
Me4Si) d : 7.94–7.91 (2H, d, J = 8.7 Hz), 7.48–7.45 (2H, d,
Η
J = 9 Hz), 4.33–4.30 (1H, t, J = 9.9 Hz), 3.91–3.88 (1H, t,
J = 9.9 Hz), 3.71–3.68 (1H, t, J = 9 Hz), 3.60–3.57 (1H, t,
J = 9.3 Hz). 13C NMR (50 MHz, CDCl3) dC: 194.8 (C=S),
186.3 (C=O), 140.9, 131.1, 129.2, 125.7, 66.4, 66.3, 51.9,
47.1. MS (EI) m/z: 269 (M+•, 12%), 139 (33), 130 (100), 86
(76). Anal. calcd for C12H12ClNO2S (269.7): C 53.43, H
4.48, N 5.19; found: C 53.33, H 5.47, N 4.35.
References
1-(4-Chlorophenyl)-2-(piperidin-1-yl)-2-thioxoethanone
(3h)19
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Yield: 21 mg (12%); yellow solid, 120–122 °C. Rf (70%
Hex/AcOEt): 0.18. IR (KBr, cm–1): 2949, 2858, 1665, 1586.
1H NMR (300 MHz, acetone-d6, Me4Si) dΗ: 8.00–7.97 (2H,
d, J = 9 Hz), 7.61–7.58 (2H, d, J = 8.7 Hz), 4.26 (2H, m),
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128 (36), 84 (100). Anal. calcd for C13H14ClNO2S (267.7):
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2-Phenyl-1-(piperidin-1-yl)ethanethione (4b)
Yield: 72 mg (39%); pale yellow solid, mp 55–57 °C. Rf
1
(90% Hex/AcOEt, eluted twice): 0.51. H NMR (300 MHz,
CDCl3, Me4Si) d : 7.33–7.18 (5H, m), 4.32 (2H, s), 4.26–
Η
4.23 (2H, m, J = 10.5 Hz), 3.57–3.53 (2H, m, J = 11.1 Hz),
2.02–1.97 (2H, bs), 1.64–1.61 (2H, m), 1.30–1.26 (2H, m).
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C 71.18, H 7.81, N 6.39; found: C 64.47, H 7.01, N 6.34.
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Yield: 69 mg (42%); yellow solid, mp 125–127 °C. Rf
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Supplementary data
Supplementary data are available with the article through the
journal Web site http://nrcresearchpress.com/doi/suppl/10.1139/
v2012-030. CCDC 819515 contains the X-ray data in CIF
format for this manuscript. These data can be obtained, free of
charge, via http://www.ccdc.cam.ac.uk/products/csd/request (Or
from the Cambridge Crystallographic Data Centre, 12 Union
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