Thioamides from 5-arylfurfural and monosubstituted piperazine derivatives (Wilgerodt-Kindler reaction)

Article abstract of DOI:10.1134/S1070428007080180

Interaction of 5-arylfurfurals or arylaldehydes with secondary amines (monosubstituted piperazines, morpholine, piperidine) and sulfur under conditions of Wilgerodt-Kindler reaction provided N-substituted thioamides of 5-arylfuran-2-carboxylic and benzoic acids.

Full text of DOI:10.1134/S1070428007080180

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2007, Vol. 43, No. 8, pp.1190−1195. © Pleiades Publishing, Ltd., 2007.
Original Russian Text © I.S. Fedorovich, N.I. Ganushchak, V.V. Karpyak, N.D. Obushchak, A.I. Lesyuk, 2007, published in Zhurnal Organicheskoi
Khimii, 2007, Vol. 43, No. 8, pp. 1196−2000.
Thioamides from 5-Arylfurfural and Monosubstituted Piperazine
Derivatives (Wilgerodt−Kindler Reaction)
I. S. Fedorovich, N. I. Ganushchak, V. V. Karpyak, N. D. Obushchak, and A. I. Lesyuk
Ivan Franko Lvov National University, Lvov, 79005 Ukraine
e-mail: obushak@in.lviv.ua
Received September 7, 2006
Abstract—Interaction of 5-arylfurfurals or arylaldehydes with secondary amines (monosubstituted piperazines,
morpholine, piperidine) and sulfur under conditions of Wilgerodt–Kindler reaction provided N-substituted
thioamides of 5-arylfuran-2-carboxylic and benzoic acids.
DOI: 10.1134/S1070428007080180
Thioamides are reactive compounds successfully used
in organic synthesis, in particular, in the preparation of
mesoionic betaines [1], thiazole derivatives [2, 3],
rhodanine [4], and other heterocycles [5], as thioacylating
reagents [6]. Owing to their versatile properties the
thioamides are used in medicine, in rubber vulcanization
as boosters, as inhibitors of metal corrosion [7].
In the present study we investigated the interaction
of substituted benzaldehydes Ia–Ie and 5-arylfurfurals
IIa–IIj with piperazine derivatives IIIa–IIIh and sulfur
under the conditions of Wilgerodt–Kindler reaction. We
also reacted aldehydes IIa–IIj with morpholine (IVa)
and piperidine (IVb). In all events thioamides V–VII
were obtained in high or moderate yields (Scheme 1).
Thioamides are prepared by various known methods
[7, 8] based on reactions of nitriles, amidoximes, imino-
esters, and imidoyl chlorides with hydrogen sulfide or
other sulfur derivatives. Wilgerodt–Kindler reaction is
among the most common procedures for thioamides
synthesis. The reaction is carried out in various
modifications [7, 9].
Sometimes benzene was used as solvent, but the best
results were obtained in reactions carried out in DMF.
The optimum ratio aldehyde (I,II):sulfur:amine was
1:1:1.3. The reaction time and temperature was adjusted
depending on the reactivity of the reagents. The process
was more vigorous with aromatic aldehydes possessing
electron-acceptor substituents. We failed to bring into
the reaction aldehydes with alkoxy substituents. In
contrast the aldehydes containing p-dimethylamino and
p-diethylamino groups gave thioamides in good yields.
With 5-arylfurfurals IIa–IIj the character of the
substituent in the aromatic ring did not significantly affect
5-Arylfurfurals were not yet brought into the
Wilgerodt–Kindler reaction. On the other hand thio-
amides containing a piperazine ring are of interest since
many among piperazine derivatives are endowed with
a biologic action [10].
Scheme 1.
NR'
R
R
+ S +HN
NR'
_
_
DMF, 60 100oC, 2 8 h
N
O
S
_
_
_
Iа Ie
Vа Vj
IIIа IIIf
I, R = 4-t-Bu (a), 3-NO2 (b), 4-NMe2 (c), 4-Cl (d), 4-OH (e); III, R' = Ac (a), Ph (b), 2-MeC6H4 (c), 3-ClC6H4 (d),
2-O2NC6H4 (e), 1-C10H7 (f); V, R' =Ac, R = 4-t-Bu (a), 3-NO2 (b), 4-NMe2 (c); R' = Ph, R = 4-Cl (d), 4-OH (e), 4-NMe2 (f);
R = 4-NMe2, R' = 2-MeC6H4 (g), 3-ClC6H4 (h), 1-C10H7 (j); R = 4-t-Bu, R' = 2-O2NC6H (i).
1190

THIOAMIDES FROM 5-ARYLFURFURAL AND MONOSUBSTITUTED PIPERAZINE DERIVATIVES
1191
the reactivity. The unsubstituted furfural is unstable
under the reaction conditions, and the reaction mixture
suffers tarring due to the opening of the furan ring in the
presence of amine. The amine nature also affected the
yield of thioamides V–VII: The reaction took less time
at the use of more basic amines [piperidine and 4-(2-
cyanoethyl)piperazine (IIIg)] (Scheme 2).
with 3- nitrophenyldiazonium chloride [11], converting
the acid obtained into the acyl chloride and reacting the
latter with morpholine.
Hence the available 5-arylfurfurals are convenient
reagents for thioamides synthesis by Wilgerodt–Kindler
reaction.
The reaction progress was monitored by TLC (eluent
hexane–acetone, 4:1), and also by qualitative tests for
carbonyl group and H2S.
EXPERIMENTAL
1H NMR spectra were registered on spectrometers
Bruker at operating frequencies 500 (Vd–Vf), 400 (Va–
Vc, Vi, and Vj), and 300 MHz (VIa, VIc, VIe, VIh, VIIa–
VIIn). Solvents used were CDCl3 (VIe and VIh), DMSO-
d6 (Va–Vc, VId–VIf, VIi, VIj, and VIIi), and DMSO-
d6–CCl4 (the other compounds). Chemical shifts were
measured with respect to the solvent signal (DMSO,
2.50 ppm) or to the internal reference.
The structure of compounds synthesized was
1
confirmed by H NMR spectra. The structure of com-
pound VIe was also proved by transforming it into 5-(3-
nitrophenyl)-furan-2-carboxylic acid morpholide (VIII)
by treating with potassium permanganate (Scheme 3).
Compound VIII was also obtained by an independent
synthesis through arylating the furan-2-carboxylic acid
Scheme 2.
HN
X
X
RC6H4
RC6H4
IVа, IVb
N
O
O
HN NR'
S
+ S
_
VIа VIj
RC6H4
_
_
DMF, 60 100oC, 2 8 h
IIIа, IIIb,
IIIg, IIIj
O
NR'
O
_
IIа IIj
N
S
_
VIIа VIIn
II, R = 3-CF3 (a), 2-Cl (b), 4-Cl (c), 2,3-Cl2 (d), 2,4-Cl2 (e), 2,5-Cl2 (f), 3,4-Cl2 (g), 4-Br (h), 2-NO2 (i), 3-NO2 (j); III,
R' = CH2CH2CN (g), 4-MeC6H4 (h); IV, X = O (a), CH2 (b); VI, X = O, R = 2,3-Cl2 (a), 2,5-Cl2 (b), 3,4-Cl2 (c), 4-Br (d),
3-NO2 (e); X = CH2, R = 4-Cl (f), 2,4-Cl2 (g), 2,5-Cl2 (h), 4-Br (i), 3-NO2 (j); VII, R' = CH2CH2CN, R = 2,3-Cl2 (a),
2,5-Cl2 (b), 2-NO2 (c), 3-NO2 (d); R' = Ac, R = 2,5-Cl2 (e), 2-NO2 (f), 3-NO2 (g); R' = Ph, R = 3-CF3 (h), 2-Cl (i), 2,5-Cl2
(j), 2-NO2 (k); R' = 4-MeC6H4, R = 3-CF3 (l), 2,5-Cl2 (m), 2-NO2 (n).
Scheme 3.
O2N
N2Cl
O2N
CuCl2
COOH
O
+
COOH
O
O
(1) SOCl2
KMnO4
N
O
O2N
(2)HN
O
VIe
O
VIII
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FEDOROVICH et al.
1192
Initial 5-arylfurfurals were obtained by procedure
from [12]. Monosubstituted piperazines were prepared
as described in [13].
N 8.95; S 10.01. C17H17ClN2S. Calculated, %: N 8.84;
S 10.12.
(4-Hydroxyphenyl)-(4-phenylpiperazin-1-yl)-
1-(2-Cyanoethyl)piperazine (IIIg). To a mixture of
20.4 ml (0.31 mol) of acrylonitrile and 20 ml of ethanol
was added gradually at cooling while stirring 25.8 g
(0.3 mol) of anhydrous piperazine. The reaction mixture
was boiled for 3 h, the solvent was distilled off, and the
residue was subjected to fractional distillation in
a vacuum. Yield 24.7 g (59%), bp 106°C (1.5 mm Hg),
nD20 1.4909.
methanethione (Ve). Yield 56%, mp 217–218°C.
1H NMR spectrum, δ, ppm: 3.19 br.s (2H, CH2NPh),
3.38 br.s (2H, CH2NPh), 3.81 br.s (2H, CH2NC=S),
4.42 br.s (2H, CH2NC=S), 6.74 d (2H, C6H4), 6.80 t (1H,
Ph), 6.92 d (2H, Ph), 7.21 t (2H, Ph), 7.17 d (2H, C6H4),
9.61 C (1H, OH). Found, %: N 9.48; S 10.65.
C17H18N2OS. Calculated, %: N 9.39; S 10.74.
(4-Dimethylaminophenyl)-(4-phenylpiperazin-1-
yl)methanethione (Vf). Yield 71%, mp 139–140°C.
1H NMR spectrum, δ, ppm: 3.00 s (6H, Me2N), 3.29 br.s
[4H, (CH2)2NPh], 3.88 br.s (2H, CH2NC=S), 4.38 br.s
(2H, CH2NC=S), 6.65 d (2H, C6H4), 6.81 t (1H, Ph),
6.92 d (2H, Ph), 7.21 t (2H, Ph), 7.24 d (2H, C6H4).
Found, %: N 13.03; S 9.77. C19H23N3S. Calculated, %:
N 12.91; S 9.85.
Thioamides V–VII. A mixture of 0.01 mol of
aldehyde I or II, 0.013 mol of secondary amine III or
IV, and 0.32 g (0.01 mol) of fine powder of sulfur in
20 ml of DMF was heated at 60–100°C with stirring till
the end of hydrogen sulfide liberation (from 2 to 8 h).
The cooled reaction mixture was diluted with water
(100 ml), the separated precipitate was filtered off and
recrystallized from ethanol with DMF added.
(4-Dimethylaminophenyl)-[4-(2-methylphenyl)-
piperazin-1-yl]methanethione (Vg). Yield 64%, mp
145–146°C. Found, %: C 70.61; H 7.59; N 12.24; S 9.36.
C20H25N3S. Calculated, %: C 70.76; H 7.42; N 12.38;
S 9.44.
1-Acetyl-4-(4-tert-butylbenzothioyl)piperazine
(Va). Yield 74%, mp 165–166°C. 1H NMR spectrum, δ,
ppm: 1.32 s (9H, Me3C), 1.99 s + 2.07 s (3H, Me),
3.48 br.s (2H, CH2NAc), 3.59 br.s + 3.64 br.s (2H,
CH2NC=S), 3.69 br.s (2H, CH2NAc), 4.23 br.s +
4.30 br.s (2H, CH2NC=S), 7.21 d (2H, C6H4), 7.37 d
(2H, C6H4). Found, %: N 9.34; S 10.45. C17H24N2OS.
Calculated, %: N 9.20; S 10.53.
(4-Dimethylaminophenyl)-[4-(3-chlorophenyl)-
piperazin-1-yl]methanethione (Vh). Yield 68%, mp
153–154°C. Found, %: C 63.62; H 6.04; N 11.52; S 9.03.
C19H22ClN3S. Calculated, %: C 63.41; H 6.16; N 11.67;
S 8.81.
1-Acetyl-4-(3-nitrobenzothioyl)piperazine (Vb).
1
Yield 50%, mp 82–83°C. H NMR spectrum, δ, ppm:
(4-tert-Butylphenyl)-[4-(2-nitrophenyl)-piperazin-
1-yl]methanethione (Vi). Yield 65%, mp 122–123°C.
1H NMR spectrum, δ, ppm: 1.32 s (9H, Me3C), 3.07 t
(2H, CH2NAr), 3.29 t (2H, CH2NAr), 3.75 t (2H,
CH2NC=S), 4.44 t (2H, CH2NC=S), 7.16 t (1H, C6H4N),
7.23 d (2H, C6H4), 7.38 d (2H, C6H4), 7.34 d (1H,
C6H4N), 7.59 t (1H, C6H4N), 7.80 d (1H, C6H4N). Found,
%: N 11.17; S 8.28. C21H25N3O2S. Calculated, %: N 10.96;
S 8.36.
2.00 s + 2.07 s (3H, Me), 3.50 br.s (2H, CH2NAc),
3.57 br.s + 3.62 br.s (2H, CH2NC=S), 3.72 br.s (2H,
CH2NAc), 4.24 br.s + 4.31 br.s (2H, CH2NC=S), 7.63–
7.74 m (2H, C6H4), 8.12–8.22 m (2H, C6H4). Found, %:
N 14.47; S 10.82. C13H15N3O3S. Calculated, %: N 14.32;
S 10.93.
1-Acetyl-4-(4-dimethylaminobenzothioyl)-
piperazine (Vc). Yield 65%, mp 118–119°C. 1H NMR
spectrum, δ, ppm: 2.04 s (3H, Me), 2.98 C (6H, Me2N),
3.57 br.s [4H, (CH2)2NAc], 3.75 br.s (2H, CH2NC=S),
4.17 br.s (2H, CH2NC=S), 6.62 d (2H, C6H4), 7.22 d
(2H, C6H4). Found, %: N 14.53; S 10.88. C15H21N3OS.
Calculated, %: N 14.42; S 11.00.
(4-Dimethylaminophenyl)-[4-(1-naphthyl)-
piperazin-1-yl]methanethione (Vj). Yield 45%, mp
1
106–107°C. H NMR spectrum, δ, ppm: 2.99 s (6H,
Me2N), 3.15 br.s [4H, (CH2)2NAr], 4.00 br.s [4H,
(CH2)2NC=S], 6.64 d (2H, C6H4), 7.12 d (1H, C10H7),
7.25 d (2H, C6H4), 7.39 t (1H, C10H7), 7.44–7.52 m (2H,
C10H7), 7.57 d (1H, C10H7), 7.83 d (1H, C10H7), 8.19 d
(1H, C10H7). Found, %: N 11.02; S 8.68. C23H25N3S.
Calculated, %: N 11.19; S 8.54.
(4-Chlorophenyl)-(4-phenylpiperazin-1-yl)-
methanethione (Vd). Yield 46%, mp 145–146°C.
1H NMR spectrum, δ, ppm: 3.20 t (2H, CH2NPh), 3.40 t
(2H, CH2NPh), 3.73 t (2H, CH2NC=S), 4.44 t (2H,
CH2NC=S), 6.81 t (1H, Ph), 6.92 d (2H, Ph), 7.22 t (2H,
Ph), 7.33 d (2H, C6H4), 7.41 d (2H, C6H4). Found, %:
[5-(2,3-Dichlorophenyl)-2-furyl]-(morpholin-4-
yl)methanethione (VIa). Yield 78%, mp 128–129°C.
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THIOAMIDES FROM 5-ARYLFURFURAL AND MONOSUBSTITUTED PIPERAZINE DERIVATIVES
1193
1H NMR spectrum, δ, ppm: 3.79 t [4H, (CH2)2N],
4.18 br.s [4H, (CH2)2O], 7.12 d (1H, furan), 7.20 d (1H,
furan), 7.40 t (1H, C6H3), 7.52 d (1H, C6H3), 7.80 d (1H,
C6H3). Found, %: N 4.17; S 9.22. C15H13Cl2NO2S.
Calculated, %: N 4.09; S 9.37.
[5-(4-Bromophenyl)-2-furyl]-(piperidin-1-yl)-
methanethione (VIi). Yield 60%, mp 137–138°C.
Found, %: C 54.72; H 4.49; N 4.05; S 9.22. C16H16BrNOS.
Calculated, %: C 54.86; H 4.60; N 4.00; S 9.15.
[5-(3-Nitrophenyl)-2-furyl]-(piperidin-1-
yl)methanethione (VIj). Yield 75%, mp 92–93°C.
Found, %: C 60.58; H 5.02; N 8.94; S 10.32.
C16H16N2O3S. Calculated, %: C 60.74; H 5.10; N 8.85;
S 10.13.
[5-(2,5-Dichlorophenyl)-2-furyl]-(morpholin-4-yl)-
methanethione (VIb). Yield 85%, mp 145–146°C.
Found, %: C 52.40; H 4.01; N 4.15; S 9.54.
C15H13Cl2NO2S. Calculated, %: C 52.64; H 3.83; N 4.09;
S 9.37.
3-{4-[5-(2,3-Dichlorophenyl)-2-furylcarbothioyl]-
piperazin-1-yl}propionitrile (VIIa). Yield 65%, mp 87–
88°C. H NMR spectrum, δ, ppm: 2.60–2.80 m [4H,
(CH2)2CN], 2.73 s [4H, (CH2)2NAlk], 4.16 br.s [4H,
(CH2)2NC=S], 7.09 d (1H, furan), 7.20 d (1H, furan),
7.40 t (1H, C6H3), 7.53 d (1H, C6H3), 7.80 d (1H, C6H3).
Found, %: C 54.70; H 4.21; N 10.60. C18H17Cl2N3OS.
Calculated, %: C 54.83; H 4.35; N 10.66.
[5-(3,4-Dichlorophenyl)-2-furyl]-(morpholin-4-
yl)methanethione (VIc). Yield 75%, mp 134–135°C.
1H NMR spectrum, δ, ppm: 3.80 t [4H, (CH2)2N],
4.16 br.s [4H, (CH2)2O], 7.05 d (1H, furan), 7.09 d (1H,
furan), 7.55 d (1H, C6H3), 7.67 d (1H, C6H3), 7.88 s
(1H, C6H3). Found, %: N 4.26; S 9.18. C15H13Cl2NO2S.
Calculated, %: N 4.09; S 9.37.
1
3-{4-[5-(2,5-Dichlorophenyl)-2-furylcarbothioyl]-
[5-(4-Bromophenyl)-2-furyl]-(morpholin-4-yl)-
methanethione (VId). Yield 82%, mp 148–149°C.
Found, %:C51.34; H 4.12; N 3.78; S 9.22. C15H14BrNO2S.
Calculated, %: C 51.15; H 4.01; N 3.98; S 9.10.
piperazin-1-yl}propionitrile (VIIb). Yield 62%, mp
1
140–141°C. H NMR spectrum, δ, ppm: 2.63 t (2H,
CH2N), 2.75 t (2H, CH2CN), 2.70 s [4H, (CH2)2NAlk],
4.15 br.s [4H, (CH2)2NC=S], 7.06 d (1H, furan), 7.22 d
(1H, furan), 7.31 d.d (1H, C6H3), 7.50 d (1H, C6H3),
7.81 d (1H, C6H3). Found, %: C 54.97; H 4.26; N 10.82.
C18H17Cl2N3OS. Calculated, %: C 54.83; H 4.35;
N 10.66.
[5-(3-Nitrophenyl)-2-furyl]-(morpholin-4-yl)-
methanethione (V²e). Yield 82%, mp 152–153°C.
1H NMR spectrum, δ, ppm: 3.88 br.s [4H, (CH2)2N],
4.10 br.s (2H, CH2O), 4.35 br.s (2H, CH2O), 6.89 d (1H,
furan), 7.21 d (1H, furan), 7.61 t (1H, C6H4), 7.96 d (1H,
C6H4), 8.18 d (1H, C6H4), 8.48 C (1H, C6H4). Found, %:
N 8.62; S 10.28. C15H14N2O4S. Calculated, %: N 8.79;
S 10.06.
3-{4-[5-(2-Nitrophenyl)-2-furylcarbothioyl]-
piperazin-1-yl}propionitrile (VIIc). Yield 65%, mp
1
134–135°C. H NMR spectrum, δ, ppm: 2.59–2.79 m
[8H, (CH2)2CN + (CH2)2NAlk], 4.07 br.s [4H,
(CH2)2NC=S], 6.89 d (1H, furan), 7.12 d (1H, furan),
7.60 t (1H, C6H4), 7.71 t (1H, C6H4), 7.83 t (2H, C6H4).
Found, %: C 58.24; H 4.77; N 14.98. C18H18N4O3S.
Calculated, %: C 58.36; H 4.90; N 15.12.
[5-(4-Chlorophenyl)-2-furyl]-(piperidin-1-yl)-
methanethione (VIf). Yield 72%, mp 108–109°C.
Found, %: C 62.80; H 5.39; N 4.67; S 10.53.
C16H16ClNOS. Calculated, %: C 62.84; H 5.27; N 4.58;
S 10.48.
3-{4-[5-(3-Nitrophenyl)-2-furylcarbothioyl]-
[5-(2,4-Dichlorophenyl)-2-furyl]-(piperidin-1-
yl)methanethione (VIg). Yield 68%, mp 103–104°C.
Found, %: C 56.34; H 4.38; N 4.18; S 9.58.
C16H15Cl2NOS. Calculated, %: C 56.48; H 4.44; N 4.12;
S 9.42.
piperazin-1-yl}propionitrile (VIId). Yield 67%, mp
94–95°C. H NMR spectrum, δ, ppm: 2.65 t (2H,
CH2N), 2.76 t (2H, CH2CN), 2.74 s [4H, (CH2)2NAlk],
4.18 br.s [4H, (CH2)2NC=S], 7.09 d (1H, furan), 7.19 d
(1H, furan), 7.70 t (1H, C6H4), 8.14 d (2H, C6H4), 8.51
C (1H, C6H4). Found, %: C 58.50; H 4.98; N 15.31.
C18H18N4O3S. Calculated, %: C 58.36; H 4.90; N 15.12.
1
[5-(2,5-Dichlorophenyl)-2-furyl]-(piperidin-1-
yl)methanethione (VIh). Yield 78%, mp 122–123°C.
1H NMR spectrum, δ, ppm: 1.81 br.s [6H, (CH2)3],
3.87 br.s (2H, CH2N), 4.28 br.s (2H, CH2N), 7.11 d (1H,
furan), 7.18 d (1H, furan), 7.23 d.d (1H, C6H3), 7.37 d
(1H, C6H3), 7.77 d (1H, C6H3). Found, %: C 56.50; H 4.60;
N 4.25. C16H15Cl2NOS. Calculated, %: C 56.48; H 4.44;
N 4.12.
1-Acetyl-4-{[5-(2,5-dichlorophenyl)-2-furyl]-
carbothioyl}piperazine (VIIe). Yield 68%, mp 165–
1
166°C. H NMR spectrum, δ, ppm: 2.09 s (3H, Me),
3.70 t [4H, (CH2)2NAC], 4.13 br.s (2H, CH2NC=S),
4.19 br.s (2H, CH2NC=S), 7.12 d (1H, furan), 7.23 d
(1H, furan), 7.33 d.d (1H, C6H3), 7.51 d (1H, C6H3),
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FEDOROVICH et al.
1194
7.84 d (1H, C6H3). Found, %: C 53.12; H 4.38; N 7.17.
C17H16Cl2N2O2S. Calculated, %: C 53.27; H 4.21; N 7.31.
furan + 2H, Ph), 7.60 t (1H, C6H4), 7.71 t (1H, C6H4),
7.81–7.89 m (2H, C6H4). Found, %: C 64.38; H 5.03;
N 10.80. C21H19N3O3S. Calculated, %: C 64.11; H 4.87;
N 10.68.
1-Acetyl-4-{[5-(2-nitrophenyl)-2-furyl]carbothio-
yl}piperazine (VIIf). Yield 68%, mp 153–154°C.
1H NMR spectrum, δ, ppm: 2.09 s (3H, Me), 3.68 br.s
[4H, (CH2)2NAC], 4.07 br.s [4H, (CH2)2NC=S], 6.90 d
(1H, furan), 7.19 d (1H, furan), 7.60 t (1H, C6H4), 7.72 t
(1H, C6H4), 7.80–7.90 m (2H, C6H4). Found, %: C 56.70;
H 4.75; N 11.80. C17H17N3O4S. Calculated, %: C 56.81;
H 4.77; N 11.69.
{[5-(2-Trifluoromethylphenyl)-2-furyl]-[(4-
methylphenyl)piperazin-1-yl]}methanethione (VIIl).
Yield 75%, mp 128–129°C. 1H NMR spectrum, δ, ppm:
2.26 C (3H, Me), 3.33 t [4H, (CH2)2NAr], 4.30 br.s [4H,
(CH2)2NC=S], 7.12 c (2H, furan), 6.82 d (2H, C6H4N),
7.02 d (2H, C6H4N), 7.57–7.69 m (2H, C6H4), 8.01 br.s
(2H, C6H4). Found, %: C 64.26; H 4.84; N 6.38.
C23H21F3N2OS. Calculated, %: C 64.17; H 4.92; N 6.51.
1-Acetyl-4-{[5-(3-nitrophenyl)-2-furyl]carbo-
thioyl}piperazine (VIIg). Yield 65%, mp 145–146°C.
1H NMR spectrum, δ, ppm: 2.09 s (3H, Me), 3.71 br.s
[4H, (CH2)2NAC], 4.15 br.s (2H, CH2NC=S), 4.21 br.s
(2H, CH2NC=S), 7.15 d (1H, furan), 7.22 d (1H, furan),
7.71 t (1H, C6H4), 8.11–8.20 m (2H, C6H4), 8.52 C (1H,
C6H4). Found, %: C 56.94; H 4.60; N 11.54. C17H17N3O4S.
Calculated, %: C 56.81; H 4.77; N 11.69.
{[5-(2,5-Dichlorophenyl)-2-furyl]-[(4-methyl-
phenyl)piperazin-1-yl]}methanethione (VIIm). Yield
68%, mp 145–146°C. 1H NMR spectrum, δ, ppm: 2.26 s
(3H, Me), 3.31 br.s [4H, (CH2)2NAr], 4.28 br.s [4H,
(CH2)2NC=S], 7.11 d (1H, furan), 7.25 d (1H, furan),
6.81 d (2H, C6H4N), 7.02 d (2H, C6H4N), 7.33 d.d (1H,
C6H3), 7.50 d (1H, C6H3), 7.83 d (1H, C6H3). Found, %:
C 61.42; H 4.49; N 6.65. C22H20Cl2N2OS. Calculated,
%: C 61.25; H 4.67; N 6.49.
{[5-(3-Trifluoromethylphenyl)-2-furyl]-(4-phenyl-
piperazin-1-yl)}methanethione (VIIh). Yield 76%, mp
1
158–159°C. H NMR spectrum, δ, ppm: 3.41 t [4H,
{[5-(2-Nitrophenyl)-2-furyl]-[(4-methylphenyl)-
piperazin-1-yl]}methanethione (VIIn). Yield 78%, mp
146–147°C. 1H NMR spectrum, δ, ppm: 2.28 s (3H, Me),
3.29 br.s [4H, (CH2)2NAr], 4.20 br.s [4H, (CH2)2NC=S],
6.92 d (1H, furan), 7.17 d (1H, furan), 6.82 d (2H,
C6H4N), 7.03 d (2H, C6H4N), 7.60 t (1H, C6H4), 7.71 t
(1H, C6H4), 7.81–7.88 m (2H, C6H4). Found, %: C 64.71;
H 5.07; N 10.49. C22H21N3O3S. Calculated, %: C 64.85;
H 5.19; N 10.31.
(CH2)2NPh], 4.30 br.s [4H, (CH2)2NC=S], 7.12 d (1H,
furan), 7.15 d (1H, furan), 6.80 t (1H, Ph), 6.92 d (2H,
Ph), 7.22 t (2H, Ph), 7.56–7.69 m (2H, C6H4), 7.98–
8.03 m (2H, C6H4). Found, %: C 63. 59; H 4.72; N 6.85.
C22H19F3N2OS. Calculated, %: C 63.45; H 4.60; N 6.73.
{[5-(2-Chlorophenyl)-2-furyl]-(4-phenylpiperazin-
1-yl)}methanethione (VIIi). Yield 70%, mp 165–166°C.
1H NMR spectrum, δ, ppm: 3.40 br.s [4H, (CH2)2NPh],
4.29 br.s [4H, (CH2)2NC=S], 7.17 d (1H, furan), 7.22 d
(1H, furan), 6.80 t (1H, Ph), 6.95 d (2H, Ph), 7.20 t (2H,
Ph), 7.37–7.48 m (2H, C6H4), 7.53 d (1H, C6H4), 7.89 d
(1H, C6H4). Found, %: C 65.59; H 5.17; N 7.21.
C21H19ClN2OS. Calculated, %: C 65.87; H 5.00; N 7.32.
Morpholin-4-yl-[5-(3-nitrophenyl)furan-2-yl]-
methanone (VIII). a. To a solution of 1.27 g (4 mmol)
of 5-(3-nitrophenyl)-2-furylmorpholinomethanethione
(VIe) in 25 ml of methanol was added 1.42 g (9 mmol)
of KMnO4 dissolved in 25 ml of water. The mixture was
boiled for 3 h. On cooling the precipitate of
manganese(IV) oxide was filtered off, the filtrate was
neutralized with acetic acid, evaporated by half, and
extracted with ether. On distilling off the solvent we
obtained compound VIII as light-yellow crystals. Yield
40%, mp 166–167°C. Found, %: C 59.34; H 4.61; N 9.33.
C15H14N2O5. Calculated, %: C 59.60; H 4.67; N 9.27.
{[5-(2,5-Dichlorophenyl)-2-furyl]-(4-phenyl-
piperazin-1-yl)}methanethione (VIIj). Yield 69%, mp
108–109°C. 1H NMR spectrum, δ, ppm: 3.40 br.s [4H,
(CH2)2NPh], 4.30 br.s [4H, (CH2)2NC=S], 7.12 d (1H,
furan), 7.24 d (1H, furan), 6.81 t (1H, Ph), 6.91 d (2H,
Ph), 7.22 t (2H, Ph), 7.33 d.d (1H, C6H3), 7.50 d (1H,
C6H3), 7.84 d (1H, C6H3). Found, %: C 60.61; H 4.21;
N 6.62. C21H18Cl2N2OS. Calculated, %: C 60.44; H 4.35;
N 6.71.
b. To 0.5 g (2 mmol) of 5-(3-nitrophenyl)furan-2-
carbonyl chloride dissolved in 5 ml of anhydrous dioxane
was added at stirring 1 ml of triethylamine and 0.52 g
(6 mmol) of morpholine. The mixture was stirred for
1 h, the precipitate was filtered off, washed with water,
and recrystallized from ethanol. Yield 0.30 g (50%), mp
166–167°C.
{[5-(2-Nitrophenyl)-2-furyl]-(4-phenylpiperazin-
1-yl)}methanethione (VIIk). Yield 60%, mp 110–
1
111°C. H NMR spectrum, δ, ppm: 3.37 br.s [4H,
(CH2)2NPh], 4.20 br.s [4H, (CH2)2NC=S], 6.81 t (1H,
Ph), 6.90–6.97 m (1H furan + 2H, Ph), 7.17–7.27 m (1H
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THIOAMIDES FROM 5-ARYLFURFURAL AND MONOSUBSTITUTED PIPERAZINE DERIVATIVES
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