New syntheses on the basis of ethyl 2-oxotetrahydrofuran-3-carboxylates

Article abstract of DOI:10.1134/S1070428008060122

Alkylation of 5-substituted ethyl 5-methyl-2-oxotetrahydrofuran-3- carboxylates with alkyl halides in the presence of sodium ethoxide gave the corresponding 3-alkyl derivatives which were converted into 3,5-substituted 5-methyl-N-(4-nitrophenyl)-2-oxotetr

Full text of DOI:10.1134/S1070428008060122

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2008, Vol. 44, No. 6, pp. 849–854. © Pleiades Publishing, Ltd., 2008.
Original Russian Text © T.V. Kochikyan, E.V. Arutyunyan, V.S. Arutyunyan, A.A. Avetisyan, 2008, published in Zhurnal Organicheskoi Khimii, 2008, Vol. 44,
No. 6, pp. 859–863.
New Syntheses on the Basis of Ethyl
2-Oxotetrahydrofuran-3-carboxylates
T. V. Kochikyan, E. V. Arutyunyan, V. S. Arutyunyan, and A. A. Avetisyan
Erevan State University, ul. Aleka Manukyana 1, Erevan, 375025 Armenia
Received April 6, 2007
Abstract—Alkylation of 5-substituted ethyl 5-methyl-2-oxotetrahydrofuran-3-carboxylates with alkyl halides
in the presence of sodium ethoxide gave the corresponding 3-alkyl derivatives which were converted into
3,5-substituted 5-methyl-N-(4-nitrophenyl)-2-oxotetrahydrofuran-3-carboxamides and 5-methyltetrahydro-
furan-2-ones. Reactions of the latter with hydrazine hydrate led to the formation of 4-hydroxypentanoic acid
hydrazides which were treated with isothiocyanates to obtain the corresponding thiosemicarbazides whose
intramolecular cyclization in the presence of aqueous alkali gave previously unknown 1,2,4-triazole-3-thiol
derivatives.
DOI: 10.1134/S1070428008060122
It is known that some carboxy lactone derivatives
possess a broad spectrum of useful properties. In par-
ticular, various esters derived from carboxy lactones
are used as propellant additives [1] and starting com-
pounds for the synthesis of heterocycles [2]. Some car-
bamoyl-substituted lactones exhibit antitumor activity
and inhibit Ehrlich ascites carcinoma and B-16 mela-
noma [3]. We previously developed procedures for the
preparation of carboxy lactones, in which the carboxy
group is separated from the lactone ring by one or two
methylene units [4–7] and examined their biological
properties. The strongest biological effect was found in
the series of ethyl 2-oxotetrahydrofuran-3-carboxylates
[3]. Obviously, the synthesis of various carboxy lac-
tones is an important problem.
With the goal of obtaining carboxy lactones in
which the carboxy group is directly attached to the
lactone ring, we performed alkylation of 5-substituted
ethyl 2-oxotetrahydrofuran-3-carboxylates Ia and Ib
and subsequent hydrolysis of the corresponding
3,5-substituted derivatives IIa–IId. The hydrolysis
products (carboxy lactones) turned out to be unstable;
therefore, they were converted into carbonyl chlorides
IIIa and IIIb, and the latter were treated with 4-nitro-
aniline to obtain N-(4-nitrophenyl)-2-oxotetrahydro-
furan-3-carboxamides IVa and IVb (Scheme 1).
Various carboxy lactone derivatives were synthesized
according to the above scheme and were analyzed for
structure–biologically activity relationships. As shown
previously, compounds Ia and Ib are convenient initial
Scheme 1.
R2
R2
COOEt
COOEt
O
COOH
O
HO–
Me
R1
Me
R1
Me
R1
O
O
O
O
Ia, Ib
IIa–IId
O
Pr
Pr
COCl
O
C6H4NO2-4
SOCl2
N
H
Me
R1
Me
R1
O
O
O
IIIa, IIIb
IVa, IVb
I, R1 = H (a), Me (b); II, R1 = Me (a, d), H (b, c); R2 = PhCH2 (a, b), Pr (c, d); III, IV, R1 = H (a), Me (b).
849

KOCHIKYAN et al.
850
Scheme 2.
R2
R2
O
COOH
O
HO–
N2H4
R1
NH2
IIa–IId
N
–CO2
Me
R1
Me
R1
H
O
Me
O
O
OH
R2
Va–Vc
VIa–VIc
V, VI, R1 = H (a, c), Me (b); R2 = PhCH2 (a, b), Pr (c).
Scheme 3.
R1
Me
N
N
O
H
H
R1
N
N
R3NCS
SH
VIa–VIc
N
N
R3
OH
R2
H
Me
OH
R2
VIIa–VIIe
S
R3
VIIIa–VIIIe
VII, VIII, R1 = H (a, c, d), Me (b, e); R2 = PhCH2 (a, b, d, e), Pr (c); R3 = Ph (a–c); CH2=CHCH2 (d, e).
materials for the preparation of heterocyclic lactones
[8–10]. While continuing studies in this line, we found
that substituted butanolides can be converted into deriv-
atives of γ-hydroxy acids, in particular hydrazides,
1,4-disubstituted thiosemicarbazides, and new hetero-
cyclic compounds. It should be noted that 1,2,4-tri-
azole analogs exhibit antitumor and fungicidal activity
[11, 12] and are successfully used for the synthesis of
optically active nonprotein amino acids [13, 14].
thin films (neat) or dispersed in mineral oil. Thin-layer
chromatography was performed on Silufol UV-254
plates using ethanol–benzene–hexane (3:3:10, A),
ethanol–benzene–acetone (2:1:6, B) or ethanol–ben-
zene (1:3, C) as eluent; spots were visualized by treat-
ment with iodine vapor. The melting points were deter-
mined on a Boetius hot stage.
Initial ethyl 2-oxotetrahydrofuran-3-carboxylates Ia
and Ib were synthesized according to the procedure
reported in [15].
Hydrolysis of esters IIa–IId, followed by decar-
boxylation and treatment of 2,4-disubstituted pentano-
lides Va–Vc with hydrazine hydrate gave the corre-
sponding hydrazides VIa–VId (Scheme 2). This reac-
tion sequence makes it possible to introduce various
substituents into the 2-position of γ-hydroxy acid and
thus extend the series of such compounds.
Ethyl 2-oxotetrahydrofuran-3-carboxylates IIa–
IId (general procedure). Compound Ia or Ib, 0.1 mol,
was added under stirring to a solution of sodium
ethoxide prepared by dissolution of 2.3 g (0.1 mol) of
metallic sodium in 100 ml of anhydrous ethanol. The
mixture was stirred for 1 h, and 0.1 mol of the corre-
sponding alkyl halide was added dropwise. After
30 min, the mixture was heated on a water bath until it
showed neutral reaction, and the solvent was distilled
off. The residue was cooled, treated with acidified
water to pH 3–4, and extracted with diethyl ether. The
extract was washed with water and dried over anhy-
drous magnesium sulfate, the solvent was removed,
and the residue was distilled under reduced pressure.
1,4-Disubstituted thiosemicarbazides VIIa–VIIe
were synthesized by reaction of hydrazides VIa–VIc
with isothiocyanates. The reaction was complete in
a short time, and the products were obtained in high
yields. Compounds VIIa–VIIe underwent intramolec-
ular cyclization by the action of aqueous alkali to give
the corresponding 1,2,4-triazole-3-thiols VIIIa–VIIIe
(Scheme 3).
All newly synthesized compounds were charac-
1
Ethyl 3-benzyl-5,5-dimethyl-2-oxotetrahydro-
furan-3-carboxylate (IIa). Yield 80%, mp 37–38°C,
bp 133–135°C (1 mm), Rf 0.44 (A), nD20 = 1.5050. IR
spectrum, ν, cm–1: 1762 (C=O, lactone); 1734 (C=O,
ester); 1130, 1174 (C–O–C); 1600 (C=Carom); 3030
(C–Harom). 1H NMR spectrum, δ, ppm: 0.93 t and 1.35 t
(3H each, CH3), 1.25 t (3H, CH2CH3), 2.10 d and
2.40 d (1H each, 4-H), 3.10 d and 3.30 d (1H each,
PhCH2), 4.23 q (2H, OCH2), 7.15 m (2H, Harom),
terized by physical constants and IR and H NMR
spectra, and their purity was checked by TLC.
EXPERIMENTAL
The 1H NMR spectra were measured from solutions
in CDCl3 on a Varian Mercury-300 spectrometer
(300 MHz). The IR spectra were recorded on a Nicolet
FTIR NEXUS instrument from samples prepared as
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NEW SYNTHESES ON THE BASIS OF ETHYL 2-OXOTETRAHYDROFURAN-...
851
7.23 m (2H, Harom). Found, %: C 69.45; H 7.21.
C16H20O4. Calculated, %: C 69.56; H 7.25.
(3 mm), nD20 = 1.4630, d420 = 1.1577. IR spectrum, ν,
cm–1: 1750 (C=O, lactone); 1730 (ClC=O); 1120, 1210
(C–O–C). Found, %: C 52.95; H 6.45; Cl 17.75.
C9H13ClO3. Calculated, %: C 52.81; H 6.36; Cl 17.85.
Ethyl 3-benzyl-5-methyl-2-oxotetrahydrofuran-
3-carboxylate (IIb). Yield 81%, bp 140–140°C
(2 mm), nD20 = 1.5085, d420 = 1.1368, Rf 0.46 (A). The
IR spectrum of IIb was analogous to that of IIa.
1H NMR spectrum, δ, ppm: 0.95 t (3H, CH3), 1.35 t
(3H, CH2CH3), 1.80 d (1H, 5-H), 2.20 d and 2.80 d
(1H each, 4-H), 3.00 d and 3.40 d (1H each, PhCH2),
4.15 q (2H, OCH2), 7.15 m (2H, Harom), 7.40 m (1H,
Harom), 7.65 m (2H, Harom). Found, %: C 68.56; H 6.85.
C15H18O4. Calculated, %: C 68.70; H 6.87.
5,5-Dimethyl-2-oxo-3-propyltetrahydrofuran-3-
carbonyl chloride (IIIb) was synthesized in a similar
way. Yield 81%, bp 89–90°C (1 mm), nD20 = 1.4650,
d240 = 1.1359. The IR spectrum of IIIb was analogous
to that of IIIa. Found, %: C 55.05; H 7.00; Cl 16.15.
C10H15ClO3. Calculated, %: C 54.92; H 6.87; Cl 16.25.
5,5-Dimethyl-N-(p-nitrophenyl)-2-oxo-3-propyl-
tetrahydrofuran-3-carboxamide (IVa). A solution
of 4.4 g (0.02 mol) of compound IIIb in 5 ml of
anhydrous acetone was added dropwise on cooling to
a mixture of 5.5 g (0.04 mol) of p-nitroaniline and
10 ml of anhydrous acetone. The mixture was stirred
for 1 h at room temperature and for 2 h on heating so
that to maintain it slightly boiling, the solvent was
distilled off, and the residue was cooled and treated
with water. The precipitate was filtered off, washed
with water, and dried. Yield 4.6 g (72%), mp 147–
149°C (from water–alcohol, 1:2), Rf 0.54 (A). IR spec-
trum, ν, cm–1: 1750 (C=O, lactone), 1690 (C=O,
amide); 1120, 1210 (C–O–C); 1605 (C=C); 3080
Ethyl 5-methyl-2-oxo-3-propyltetrahydrofuran-
3-carboxylate (IIc). Yield 80%, bp 89–91°C (2 mm),
nD20 = 1.4460, d420 = 1.0547, Rf 0.56 (A). IR spectrum, ν,
cm–1: 1750 (C=O, lactone); 1720 (C=O, ester); 1120,
1210 (C–O–C). 1H NMR spectrum, δ, ppm: 0.95 t (3H,
CH2CH3), 1.10 t (3H, OCH2CH3), 1.25 d (3H, 5-CH3),
1.75 d (1H, 5-H), 2.09 q (2H, CH2CH2CH3), 3.05 d
and 3.65 d (1H each, 4-H), 4.00 d (2H, OCH2), 4.20 d
(2H, 3-CH2). Found, %: C 61.80; H 8.20. C11H18O4.
Calculated, %: C 61.68; H 8.41.
Ethyl 5,5-dimethyl-2-oxo-3-propyltetrahydro-
furan-3-carboxylate (IId). Yield 78%, bp 99°C
(2 mm), nD20 = 1.4450, d420 = 1.0373, Rf 0.59 (A). The
IR spectrum of IId was analogous to that of IIc.
1H NMR spectrum, δ, ppm: 1.00 t (3H, CH2CH3),
1.20 t (3H, OCH2CH3), 1.35 d (6H, 5-CH3), 2.05 q
(2H, CH2CH2CH3), 2.20 d and 2.40 d (1H each, 4-H),
4.10 d (2H, OCH2), 4.35 d (2H, 3-CH2). Found, %:
C 63.30; H 8.65. C12H20O4. Calculated, %: C 63.16;
H 8.77.
1
(C–Harom); 3280, 3340 (NH). H NMR spectrum, δ,
ppm: 1.00 t (3H, CH2CH3), 1.25 d (6H, 5-CH3), 2.10 q
(2H, CH2CH2CH3), 2.15 d and 2.50 d (1H each, 4-H),
4.40 d (2H, 3-CH2), 7.25 m (2H, Harom), 7.50 m (2H,
Harom), 13.02 (1H, NH). Found, %: C 60.15; H 6.10;
N 8.90. C16H20N2O5. Calculated, %: C 60.00; H 6.25;
N 8.75.
5-Methyl-N-(p-nitrophenyl)-2-oxo-3-propyltetra-
hydrofuran-3-carboxamide (IVb) was synthesized in
a similar way. Yield 67%, mp 123–125°C (from water–
alcohol, 1:2), Rf 0.50 (A). The IR spectrum of IVb
5-Methyl-2-oxo-3-propyltetrahydrofuran-3-car-
bonyl chloride (IIIa). Compound IId, 16.5 g
(0.073 mol), was added to a 40% aqueous solution of
7.7 g (0.193 mol) of sodium hydroxide, and the mix-
ture was stirred for 30 min at 20–25°C and for 2 h at
70–75°C. The mixture was cooled, acidified to pH 1–2
with hydrochloric acid, and extracted with diethyl
ether. The extract was washed with water, dried over
anhydrous magnesium sulfate, and evaporated, 50 ml
of anhydrous benzene, 9.6 g (0.08 mol) of thionyl
chloride, and 0.7 ml of dimethylformamide were added
to the residue, and the mixture was left to stand for 1 h
at room temperature and was then heated to the boiling
point over a period of 3 h. The mixture was maintained
boiling for 1 h, the solvent was removed under a resi-
dual pressure of 20–30 mm, and the residue was dis-
tilled in a vacuum. Yield 12.4 g (83%), bp 113–115°C
1
was analogous to that of IVa. H NMR spectrum, δ,
ppm: 0.98 t (3H, CH2CH3), 1.10 t (3H, 5-CH3), 1.80 m
(1H, 5-H), 2.05 q (2H, CH2CH2CH3), 2.40 d and
3.10 d (1H each, 4-H), 4.35 d (2H, 3-CH2), 7.00 m
(2H, Harom), 7.35 m (2H, Harom), 13.05 (1H, NH).
Found, %: C 58.95; H 5.75; N 9.30. C15H18O5N2. Cal-
culated, %: C 58.82; H 5.88; N 9.15.
3,5-Disubstituted 5-methyl-2-oxotetrahydro-
furan-2-ones Va–Vc (general procedure). Ester IIa–
IId, 0.066 mol, was added dropwise to a 30% aqueous
solution of 6.2 g (0.0.155 mol) of sodium hydroxide,
and the mixture was stirred for 30 min at 20–25°C and
for 4 h on heating on a boiling water bath. The mixture
was cooled, acidified with hydrochloric acid to pH 1–
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KOCHIKYAN et al.
852
2, and extracted with diethyl ether. The extract was
washed with water and dried over anhydrous magne-
sium sulfate, the solvent was removed, and the residue
was distilled under reduced pressure.
NH2, OH). Found, %: C 55.05; H 10.45; N 16.15.
C8H18N2O2. Calculated, %: C 55.17; H 10.34; N 16.09.
Thiosemicarbazides VIIa–VIIe. A mixture of
0.014 mol of hydrazide VIa–VIc and 0.015 mol of
phenyl or allyl isothiocyanate in 25 ml of ethanol was
vigorously stirred on heating until it became homo-
geneous and was then heated for 1 h at 75–80°C. After
cooling, the precipitate was filtered off, washed with
ethanol, and dried.
3-Benzyl-5-methyltetrahydrofuran-2-one (Va).
Yield 88%, bp 105–106°C (1 mm), Rf 0.43 (A), nD20
=
1.5235, d240 = 1.0858. IR spectrum, ν, cm–1: 1750
(C=O, lactone); 1121, 1180 (C–O–C); 1600 (C=Carom);
1
3030 (C–Harom). H NMR spectrum, δ, ppm: 0.93 t
(3H, CH3), 1.55 m and 1.80 m (1H each, 3-H, 5-H),
2.15 d and 2.55 d (1H each, 4-H), 3.05 d and 3.35 d
(1H each, PhCH2), 7.15 m (2H, Harom), 7.40 m (1H,
2-(2-Benzyl-4-hydroxypentanoyl)-N-phenylhy-
drazinecarbothioamide (VIIa). Yield 80%, mp 150–
152°C (from ethanol), Rf 0.63 (C). IR spectrum, ν,
cm–1: 1654 (C=O); 1600 (C=Carom); 3030 (C–Harom);
Harom), 7.55 m (2H, Harom). Found, %: C 75.68; H 7.33.
1
C12H14O2. Calculated, %: C 75.79; H 7.37.
3144, 3400, 3450 (NH, OH). H NMR spectrum, δ,
ppm: 1.10 d (3H, CH3), 1.45 d and 1.80 d (1H each,
CH2), 2.60 m (1H, CH2CH), 2.90 m (CH2C6H5),
3.70 m (1H, CHOH), 4.75 s (1H, OH), 7.00–7.25 m
(2H, Harom), 7.45 m (2H, Harom), 9.35 s (2H, NH),
9.85 s (1H, NH). Found, %: C 64.00; H 6.30; N 11.86;
S 8.82. C19H23N3O2S. Calculated, %: C 63.87; H 6.44;
N 11.76; S 8.96.
3-Benzyl-5,5-dimethyltetrahydrofuran-2-one
(Vb). Yield 83%, bp 120–121°C (2 mm), mp 44–46°C,
Rf 0.52 (A). The IR spectrum of Vb was analogous to
1
that of Va. H NMR spectrum, δ, ppm: 1.35 d (6H,
5-CH3), 1.75 m (1H, 3-H), 2.05 d and 2.70 d (1H each,
4-H), 3.05 d and 3.18 d (1H each, PhCH2), 7.15 m
(2H, Harom), 7.25 m (2H, Harom). Found, %: C 76.38;
H 7.88. C13H16O2. Calculated, %: C 76.47; H 7.84.
2-(2-Benzyl-4-hydroxy-4-methylpentanoyl)-N-
phenylhydrazinecarbothioamide (VIIb). Yield 90%,
mp 142–143.5°C (from water–alcohol, 3:1), Rf 0.68
(C). The IR spectrum of VIIb was analogous to that of
5-Methyl-3-propyltetrahydrofuran-2-one (Vc).
Yield 10.7 g (75%), bp 107–108°C (13 mm). nD20
=
1.4350 [16].
1
VIIa. H NMR spectrum, δ, ppm: 1.15 d (3H, CH3),
2-Substituted 4-hydroxypentanoic acid hydra-
zides VIa–VIc (general procedure). 3,5-Substituted
5-methyltetrahydrofuran-2-one Va–Vc, 0.13 mol, was
dissolved in 35 ml of ethanol, 11.2 g of 85% hydrazine
hydrate was added, and the mixture was vigorously
stirred, left to stand for 0.5 h at 20–25°C, and heated
for 2 h on a boiling water bath. After cooling, the
precipitate was filtered off, washed with ethanol,
and dried.
2.00 d and 2.50 d (1H each, CH2), 2.70 m (1H,
CH2CH), 2.90 m (CH2C6H5), 4.70 s (1H, OH), 7.00–
7.30 m (8H, Harom), 7.60 m (2H, Harom), 9.35 s (2H,
NH), 9.95 s (1H, NH). Found, %: C 64.55; H 6.65;
N 11.45; S 8.44. C20H25N3O2S. Calculated, %:
C 64.69; H 6.74; N 11.32; S 8.62.
2-(4-Hydroxy-2-propylpentanoyl)-N-phenylhy-
drazinecarbothioamide (VIIc). Yield 91%, mp 185–
186°C (from ethanol), Rf 0.67 (C). The IR spectrum of
2-Benzyl-4-hydroxypentanehydrazide (VIa).
Yield 69%, mp 157–159°C (from ethanol), Rf 0.54 (B).
IR spectrum, ν, cm–1: 1654 (C=O), 1620 (C=Carom),
3030 (C–Harom), 3100–3400 (NH, NH2, OH). Found,
%: C 65.00; H 8.00; N 12.48. C12H18N2O2. Calculated,
%: C 64.87; H 8.11; N 12.61.
1
VIIc was analogous to that of VIIa. H NMR spec-
trum, δ, ppm: 0.92 d (3H, CH3), 1.15 t (3H, CH2CH3),
2.05 q (2H, CH2CH2CH3), 2.15 d (2H, CHCH2),
2.65 m (1H, CH), 3.40 s (1H, CHOH), 3.85 d (2H,
CH2CH2CH3), 4.20 s (1H, OH), 6.80 m (2H, Harom),
7.25 m (3H, Harom), 7.70 s (1H, NH), 9.00 s (1H, NH),
9.60 s (1H, NH). Found, %: C 58.35; H 7.56; N 13.67;
S 10.17. C15H23N3O2S. Calculated, %: C 58.25;
H 7.44; N 13.59; S 10.37.
2-Benzyl-4-hydroxy-4-methylpentanehydrazide
(VIb). Yield 70%, mp 104–106°C (from ethanol),
Rf 0.58 (C). The IR spectrum of VIb was analogous to
that of VIa. Found, %: C 65.95; H 8.60; N 11.67.
C13H20N2O2. Calculated, %: C 66.10; H 8.48; N 11.86.
N-Allyl-2-(2-benzyl-4-hydroxypentanoyl)hydra-
zinecarbothioamide (VIId). Yield 92%, mp 144–
145°C (from water–alcohol, 3:1), Rf 0.64 (C). IR spec-
trum, ν, cm–1: 1695 (C=O); 1640 (C=C); 1600
(C=Carom); 3030 (C–Harom); 3080 (=CH2); 3180, 3290,
4-Hydroxy-2-propylpentanehydrazide (VIc).
Yield 85%, mp 88–89°C (from ethanol), Rf 0.53 (A).
IR spectrum, ν, cm–1: 1654 (C=O), 3100–3400 (NH,
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NEW SYNTHESES ON THE BASIS OF ETHYL 2-OXOTETRAHYDROFURAN-...
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1
3500 (NH, OH). H NMR spectrum, δ, ppm: 1.05 d
(3H, CH3), 1.40 d and 1.65 d (1H each, CH2), 2.60 m
(1H, CH2CH), 2.85 m (CH2C6H5), 3.65 m (1H,
CHOH), 4.05 m (2H, CH2N), 4.45 s (1H, OH), 5.05 d
and 5.15 d (1H each, =CH2), 5.80 m (1H, CH=), 7.05–
7.25 m (5H, Harom), 8.95 s (2H, NH), 9.60 s (1H, NH).
Found, %: C 59.95; H 7.05; N 12.98; S 9.83.
C16H23N3O2S. Calculated, %: C 59.81; H 7.17;
N 13.08; S 9.97.
Harom), 13.43 s (1H, SH). Found, %: C 67.85; H 6.40;
N 11.77; S 8.95. C20H23N3OS. Calculated, %: C 67.99;
H 6.52; N 11.90; S 9.06.
5-(3-Hydroxy-1-propylbutyl)-4-phenyl-4H-1,2,4-
triazole-3-thiol (VIIIc). Yield 80%, mp 141–143°C
(from water–alcohol, 1:1), Rf 0.67 (C). IR spectrum, ν,
cm–1: 1570 (C=N), 1600 (C=Carom), 3030 (C–Harom),
1
3100–3300 (OH). H NMR spectrum, δ, ppm: 0.97 d
(3H, CH3), 1.15 t (3H, CH2CH3), 2.10 q (2H,
CH2CH3), 2.18 d (2H, CHCH2), 2.95 m (1H, 5-CH),
3.60 s (1H, CHOH), 4.00 d (2H, CH2CH2CH3), 4.15 s
(1H, OH), 6.80 m (2H, Harom), 7.20 m (1H, Harom),
7.35 m (2H, Harom), 13.25 s (1H, SH). Found, %:
C 61.75; H 7.15; N 14.63: S 10.77. C15H21N3OS. Cal-
culated, %: C 61.86; H 7.22; N 14.43; S 10.99.
N-Allyl-2-(2-benzyl-4-hydroxy-4-methylpenta-
noyl)hydrazinecarbothioamide (VIIe). Yield 80%,
mp 134–135°C (from water–alcohol, 3:1), Rf 0.67 (C).
The IR spectrum of VIIe was analogous to that of
1
VIId. H NMR spectrum, δ, ppm: 1.10 d (6H, CH3),
1.30 d and 1.95 d (1H each, CH2), 2.65 m (1H,
CH2CH), 2.85 m (CH2C6H5), 3.90 d and 4.20 d (1H
each, CH2N), 4.00 s (1H, OH), 5.00 d and 5.15 d (1H
each, =CH2), 5.80 m (1H, CH=), 7.10–7.25 m (5H,
4-Allyl-5-(1-benzyl-3-hydroxybutyl)-4H-1,2,4-
triazole-3-thiol (VIIId). Yield 73%, mp 128–129.5°C
(from water–alcohol, 1:1), Rf 0.65 (C). IR spectrum, ν,
cm–1: 1564 (C=N), 1600 (C=Carom), 1640 (C=C), 3030
H
arom), 7.75 s (1H, NH), 8.95 s (1H, NH), 9.65 s (1H,
1
NH). Found, %: C 61.00; H 7.35; N 12.64; S 9.36.
C17H25N3O2S. Calculated, %: C 60.90; H 7.46;
N 12.54; S 9.55.
(C–Harom), 3080 (=CH2), 3150–3360 (OH). H NMR
spectrum, δ, ppm: 1.05 d (3H, CH3), 1.65 d (2H, CH2),
2.95 m (CH2C6H5), 3.20 m (1H, CH2CH), 3.65 s (1H,
CHOH), 4.20 s (1H, OH), 4.30–4.43 m (2H, CH2N),
4.85 d and 5.00 d (1H each, =CH2), 5.60 m (1H, CH=),
7.00–7.20 m (5H, Harom), 13.30 s (1H, SH). Found, %:
C 63.25; H 7.05; N 13.62; S 10.56. C16H21N3OS. Cal-
culated, %: C 63.37; H 6.93; N 13.86; S 10.56.
4,5-Disubstituted 4H-1,2,4-triazole-3-thiols
VIIIa–VIIIe (general procedure). A mixture of a 10%
aqueous solution of sodium hydroxide (0.5 g of NaOH
in 4.5 ml of water) and 0.011 mol of thiosemicarbazide
VIIa–VIIe was heated for 4 h on a boiling water bath.
The mixture was cooled and acidified with hydro-
chloric acid to pH 1–2, and the precipitate was filtered
off, washed with water, and dried.
4-Allyl-5-(1-benzyl-3-hydroxy-3-methylbutyl)-
4H-1,2,4-triazole-3-thiol (VIIIe). Yield 75%,
mp 164–165°C (from water–alcohol, 2:3), Rf 0.62 (C).
The IR spectrum of VIIId was analogous to that of
5-(1-Benzyl-3-hydroxybutyl)-4-phenyl-4H-1,2,4-
triazole-3-thiol (VIIIa). Yield 83%, mp 207–209°C
(from water–alcohol, 1:2), Rf 0.65 (C). IR spectrum, ν,
cm–1: 1570 (C=N), 1600 (C=Carom), 3030 (C–Harom),
1
VIIIc. H NMR spectrum, δ, ppm: 1.00 d (6H, CH3),
1.65 d and 2.00 d (1H each, CH2), 2.15 m (1H,
CH2CH), 2.90 m (CH2C6H5), 4.00 br.s (1H, OH),
4.35 d and 4.50 d (2H, CH2N), 5.00 m (2H, =CH2),
5.60 m (1H, CH=), 7.05 m (2H, Harom), 7.20 m (3H,
1
3100–3300 (OH). H NMR spectrum, δ, ppm: 1.00 d
(3H, CH3), 1.63 d and 1.90 d (1H each, CH2), 2.75 m
(1H, CH2CH), 2.93 m (CH2C6H5), 3.60 s (1H,
CHOH), 4.10 s (1H, OH), 6.80 m (2H, Harom), 7.18 m
(6H, Harom), 7.40 m (2H, Harom), 13.45 s (1H, SH).
Found, %: C 67.35; H 6.30; N 12.24; S 9.31.
C19H21N3OS. Calculated, %: C 67.26; H 6.19; N 12.39;
S 9.44.
Harom), 13.43 s (1H, SH). Found, %: C 64.25; H 7.15;
N 13.00; S 9.85. C17H23N3OS. Calculated, %: C 64.35;
H 7.26; N 13.25; S 10.09.
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