Synthesis of heterocycles from arylation products of unsaturated compounds: XVIII. 5-Arylfuran-2-carboxylic acids and their application in the synthesis of 1,2,4-thiadiazole, 1,3,4-oxadiazole, and [1,2,4]triazolo[3,4-b][1,3,4] thiadiazole derivatives

Article abstract of DOI:10.1134/S1070428009040125

Arylation of furan-2-carboxylic acid or its methyl ester with arenediazonium chlorides in the presence of copper(II) chloride gave the corresponding 5-arylfuran-2-carboxylic acids or methyl 5-arylfuran-2- carboxylates. 5-Arylfuran-2-carbonyl chlorides rea

Full text of DOI:10.1134/S1070428009040125

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2009, Vol. 45, No. 4, pp. 541–550. © Pleiades Publishing, Ltd., 2009.
Original Russian Text © Yu.I. Gorak, N.D. Obushak, V.S. Matiichuk, R.Z. Lytvyn, 2009, published in Zhurnal Organicheskoi Khimii, 2009, Vol. 45, No. 4,
pp. 555–563.
Synthesis of Heterocycles from Arylation Products
of Unsaturated Compounds: XVIII.* 5-Arylfuran-2-carboxylic
Acids and Their Application in the Synthesis of 1,2,4-Thiadiazole,
1,3,4-Oxadiazole, and [1,2,4]Triazolo[3,4-b][1,3,4]thiadiazole
Derivatives
Yu. I. Gorak, N. D. Obushak, V. S. Matiichuk, and R. Z. Lytvyn
Ivana Franko Lviv National University, ul. Kirilla i Mefodiya 6, Lviv, 79005 Ukraine
e-mail: obushak@in.lviv.ua
Received April 11, 2008
Abstract—Arylation of furan-2-carboxylic acid or its methyl ester with arenediazonium chlorides in the
presence of copper(II) chloride gave the corresponding 5-arylfuran-2-carboxylic acids or methyl 5-arylfuran-2-
carboxylates. 5-Arylfuran-2-carbonyl chlorides reacted with potassium thiocyanate and then with 5-methyl-1,2-
oxazol-3-amine to give 5-aryl-N-[3-(2-oxopropyl)-1,2,4-thiadiazol-5-yl]furan-2-carboxamides as a result of
recyclization of intermediate isoxazolylthiourea derivatives. The reactions of 5-arylfuran-2-carbonyl chlorides
with 5-(2-furyl)-1H-tetrazole involved opening of the tetrazole ring with elimination of nitrogen molecule and
led to the formation of 2-(5-arylfuran-2-yl)-5-(2-furyl)-1,3,4-oxadiazoles. 3-Substituted 6-(5-arylfuran-2-yl)-
[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles were obtained by condensation of 5-arylfuran-2-carboxylic acids with
5-substituted 4-amino-4H-1,2,4-triazole-3-thiols in phosphoryl chloride.
DOI: 10.1134/S1070428009040125
Interest in arylation of furan derivatives is largely
determined by prospects in searching for biologically
active substances among compounds of the furan
series. It is known than many furan derivatives are
used as medicines [2–5]. Arylfuran fragments are pres-
ent in molecules of such medical agents as Nitrafudan,
Dantrolene, Clodanolene, and Azimilide. Many aryl-
furan compounds display a broad spectrum of biologi-
cal activity [5–11].
ing 5-aryl-substituted derivatives IVa–IVj and Va–Vk
(Scheme 1) in 40–70% yields which are fairly good for
Meerwein reaction. The best yields in the arylation of
furan-2-carboxylic acid (II) were obtained with arene-
diazonium salts containing a nitro group or two halo-
gen atoms in the aromatic ring, whereas ester III was
appropriate for the arylation with monohalo-substi-
tuted and trifluoromethylbenzenediazonium chlorides.
Alkaline hydrolysis of methyl 5-arylfuran-2-carbox-
ylates Va–Vk gave the corresponding acids IVk–IVu,
and acids IVa–IVh, IVk, and IVm–IVt were con-
verted into 5-arylfuran-2-carbonyl chlorides VIa–VIh,
VIk, and VIm–VIt (Scheme 2, see table).
A convenient method for the synthesis of arylfurans
is based on catalytic arylation of furan derivatives with
arenediazonium salts according to Meerwein [1, 10–
12]. Furan-2-carboxylic acid [13–15] and its methyl
ester [10, 14] can also be subjected to arylation with
arenediazonium salts. In the present work we extended
the scope of this reaction with a view to explore syn-
thetic potential of the arylation products. Arenediazo-
nium chlorides Ia–Iu reacted with furan-2-carboxylic
acid (II) or methyl furan-2-carboxylate (III) in the
presence of copper(II) chloride to give the correspond-
Acid chlorides VI were used to synthesize hetero-
cycles having arylfuran fragments. Acyl isothiocy-
anates VIIa–VIIk generated in situ from acid chlo-
rides VIb, VIc, VIe–VIh, VIn–VIp, VIr, and VIs and
potassium thiocyanate reacted with 5-methyl-1,2-
oxazol-3-amine (VIII). The expected products of this
reaction, N-acylthioureas IXa–IXk, were not isolated,
for they underwent recyclization involving opening of
the 1,2-oxazole ring and closure of 1,2,4-thiadiazole
* For communication XVII, see [1].
541

GORAK et al.
542
Scheme 1.
COOH
N2 Cl–
O
CuCl2, H2O, Me2CO
R
R
+
COOH
O
Ia–Ij
II
IVa–IVj
COOMe
N2 Cl–
O
CuCl2, H2O, Me2CO
R
R
+
COOMe
III
O
Ik–Iu
Va–Vk
COOH
(1) KOH, H2O
(2) HCl
O
R
IVk–IVu
I, IV, R = 2-O2N (a), 3-O2N (b), 4-O2N (c), 2,3-Cl2 (d), 2,4-Cl2 (e), 2,5-Cl2 (f), 3,4-Cl2 (g), 2-Cl-4-O2N (h), 2-O2N-4-MeO (i),
2-O2N-4-Me (j), 2-F (k), 3-F (l), 4-F (m), 2-Cl (n), 3-Cl (o), 4-Cl (p), 4-Br (q), 2-F3C (r), 3-F3C (s), 2-Cl-5-F3C (t), 3-F3C-4-Cl (u);
V, R = 2-F (a), 3-F (b), 4-F (c), 2-Cl (d), 3-Cl (e), 4-Cl (f), 4-Br (g), 2-F3C (h), 3-F3C (i), 2-Cl-5-F3C (j), 3-F3C-4-Cl (k).
Scheme 2.
COCl
SOCl2, benzene
O
IVa–IVh, IVk, IVm–IVt
R
VIa–VIh, VIk, VIm–VIt
ring [16] to produce finally 5-aryl-N-[3-(2-oxopropyl)-
1,2,4-thiadiazol-5-yl]furan-2-carboxamides Xa–Xk
(Scheme 3).
We also tried to synthesize 1,3,4-oxadiazoles hav-
ing an arylfuran fragment. Derivatives of 1,3,4-oxadi-
azoles are known as biologically active substances
[2, 3] and intermediate products in the preparation of
heat-resistant polymers, scintillators, luminophores,
dyes, and photochromic materials [17]. For this pur-
pose, we followed an approach based on recyclization
of tetrazoles [17, 18]. In fact, 5-arylfuran-2-carbonyl
chlorides VIa, VIh, VIq, VIr, and VIt reacted with
Scheme 3.
O
COCl
KSCN
O
O
N
C
S
R
R
VIb, VIc, VIe–VIh, VIn–VIp, VIr, VIs
VIIa–VIIk
H2N
Me
O
Me
O
O
N
O
Me
H
N
VIII
N
O
O
HN
HN
O
R
R
N
N
S
S
IXa–IXk
Xa–Xk
VII, X, R = 3-O2N (a), 4-O2N (b), 2-Cl-4-O2N (c), 2-Cl (d), 3-Cl (e), 4-Cl (f), 2,4-Cl2 (g), 2,5-Cl2 (h), 3,4-Cl2 (i),
2-F3C (j), 3-F3C (k).
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SYNTHESIS OF HETEROCYCLES FROM ARYLATION ... XVIII.
543
Scheme 4.
··
N
N
N
N
O
R
COCl
O
N
O
N
+
N
R
O
N
H
O
VIa, VIh, VIq, VIr, VIt
XI
O
O
O
O
–N2
N
N
N
N
R
R
O
O
O
R
O
O
N
N
XIIa–XIIe
XII, R = 2-O2N (a), 2-Cl-4-O2N (b), 4-Br (c), 2-F3C (d), 2-Cl-5-F3C (e).
Scheme 5.
S
N
N
N
COOH
POCl3
N
O
O
HS
R2
N
+
N
N
R1
R1
R2
NH2
XIIIa–XIIIe
IVa–IVc, IVg, IVm, IVn, IVp, IVs
XIVa–XIVn
XIII, R2 = 2-methylfuran-3-yl (a), 2-furyl (b), Ph (c), PhCH2 (d), Pr (e); XIV, R1 = 2-O2N, R2 = 2-methylfuran-3-yl (a), Ph (b);
R1 = 3-O2N, R2 = 2-methylfuran-3-yl (c); R1 = 4-O2N, R2 = 2-methylfuran-3-yl (d), 2-furyl (e); R1 = 2-Cl, R2 = Ph (f), 2-methylfuran-
3-yl (g), PhCH2 (h); R1 = 4-Cl, R2 = Pr (i), 2-methylfuran-3-yl (j), 2-furyl (k); R1 = 4-F, R2 = 2-furyl (l); R1 = 3-F3C, R2 =
2-furyl (m); R1 = 3,4-Cl2, R2 = PhCH2 (n).
5-(2-furyl)-1H-tetrazole on heating in pyridine to give
compounds XIIa–XIIe (Scheme 4). The reactions
were accompanied by evolution of nitrogen. In the first
step, acylation of 5-(2-furyl)-1H-tetrazole (XI) with
acid chloride VI is likely to afford 2-(5-arylfuran-2-
yl)-5-(2-furyl)-2H-tetrazole, and decomposition of the
latter with elimination of nitrogen molecule and subse-
quent recyclization leads to the formation of 1,3,4-oxa-
diazoles XIIa–XIIe. Presumably, elimination of nitro-
gen molecule and oxadiazole ring closure follow
a concerted mechanism [19].
XIIIa–XIIIe with furancarboxylic acids IVa–IVc,
IVg, IVm, IVn, IVp, and IVs in POCl3 and obtained
the corresponding 6-(5-arylfuran-2-yl)[1,2,4]triazolo-
[3,4-b][1,3,4]thiadiazoles XIVa–XIVn (Scheme 5).
The results of our present study have demonstrated
that Meerwein reaction is suitable for arylation of
furan-2-carboxylic acid or its ester and that 5-aryl-
furan-2-carboxylic acids having various substituents in
the benzene ring are convenient reagents for the design
of heterocyclic compounds with an arylfuryl fragment.
It is known that fused [1,2,4]triazolo[3,4-b][1,3,4]-
thiadiazole system is a pharmacophore [20]. Biological
activity of some [1,2,4]triazolo[3,4-b][1,3,4]thiadia-
zole derivatives has stimulated further studies in the
fields of their synthesis and properties [21]. As follows
from published data [21], the most convenient method
for building up [1,2,4]triazolo[3,4-b][1,3,4]thiadiazole
system is cyclization of carboxylic acids with 4-amino-
4H-1,2,4-triazole-3-thiols. We examined reactions of
5-substituted 4-amino-4H-1,2,4-triazole-3-thiols
EXPERIMENTAL
1
The H NMR spectra were recorded on Varian
Mercury (400 MHz; compounds IV, XII, XIV) and
Bruker DRX-500 spectrometers (500 MHz; com-
pounds X) from solutions in DMSO-d6 or DMSO-d6–
CCl4 (1:3) (IV, XII). The chemical shifts were meas-
ured relative to tetramethylsilane as internal reference.
The mass spectra (chemical ionization) were obtained
on an Agilent 1100 GC–MS system.
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GORAK et al.
544
Yields and melting points of 5-arylfuran-2-carbonyl chlo-
rides VIa–VIh, VIk, and VIm–VIt
5-(3-Nitrophenyl)furan-2-carboxylic acid (IVb).
Yield 43%, mp 265–267°C (from EtOH–DMF);
published data: mp 265–268 [15], 244°C [13]. Found,
%: C 56.38; H 3.09; N 6.17. C11H7NO5. Calculated, %:
C 56.66; H 3.03; N 6.01.
Comp. no. Yield, % bp, °C (mm)
mp, °C (solvent)
VIa
VIb
VIc
VId
VIe
VIf
83
86
80
84
90
75
82
79
89
89
79
75
77
74
84
71
79
–
–
–
074–75 (benzene)
111–112 (benzene)
147–148 (benzene)
5-(4-Nitrophenyl)furan-2-carboxylic acid (IVc).
Yield 68%, mp 252–253°C (from EtOH–DMF); pub-
lished data [22]: mp 251–252°C.
177–180 (2) 083–84 (hexane)
170–175 (2) 090–91 (benzene)
175–180 (2) 129–130 (benzene)
189–194 (2) 097–98 (benzene)
5-(2,3-Dichlorophenyl)furan-2-carboxylic acid
(IVd). Yield 51%, mp 259–260°C (from EtOH–DMF);
1
published data [23]: mp 259–261°C. H NMR spec-
VIg
VIh
VIk
VIm
VIn
VIo
VIp
VIq
VIr
VIs
VIt
trum, δ, ppm: 7.20 d (1H, furan, J = 3.4 Hz), 7.24 d
(1H, furan, J = 3.4 Hz), 7.39 pseudotriplet (1H, 5′-H),
7.50 d (1H, 4′-H, J = 7.8 Hz), 7.92 d (1H, 6′-H, J =
6.8 Hz). Found, %: C 51.18; H 2.22. C11H6Cl2O3. Cal-
culated, %: C 51.39; H 2.35.
–
145–146 (benzene)
140–144 (2) 074–75 (hexane)
144–149 (2) 071–72 (hexane)
154–159 (2) 057–58 (benzene)
170–175 (2) 053–54 (benzene)
166–167 (2) 064–65 (benzene)
183–186 (2) 076–77 (benzene)
5-(2,4-Dichlorophenyl)furan-2-carboxylic acid
(IVe). Yield 49%, mp 216°C (from EtOH–DMF).
Found, %: C 51.13; H 2.47; Cl 27.65. C11H6Cl2O3.
Calculated, %: C 51.39; H 2.35; Cl 27.58.
155–158 (2)
–
5-(2,5-Dichlorophenyl)furan-2-carboxylic acid
(IVf). Yield 56%, mp 226–227°C (from EtOH–DMF).
Found, %: C 51.48; H 2.43; Cl 27.63. C11H6Cl2O3.
Calculated, %: C 51.39; H 2.35; Cl 27.58.
150–155 (2) 077–78 (hexane)
160–165 (2) 091–92 (benzene)
5-Arylfuran-2-carboxylic esters IVa–IVj and
methyl 5-arylfuran-2-carboxylates Va–Vk (general
procedure). A solution of arenediazonium chloride Ia–
Ij or Ik–Iu, prepared by diazotization (HCl, NaNO2)
of 0.21 mol of the corresponding aromatic amine, was
cooled to 0–5°C and added dropwise under stirring to
a solution of 22.4 g (0.2 mol) of furan-2-carboxylic
acid (II) or 25.2 g (0.2 mol) of methyl furan-2-car-
boxylate (III) and 2 g of copper(II) chloride dihydrate
(CuCl2·2H2O) in 80 ml of acetone. During the addi-
tion, the temperature was maintained in the range from
20 to 30°C so that the rate of evolution of nitrogen was
2–3 bubbles per second. When nitrogen no longer
evolved, the mixture was poured into 200 ml water,
and the precipitate was filtered off (compounds IVa–
IVj) or the product was isolated by vacuum distillation
(Va–Vk) and purified by recrystallization.
5-(3,4-Dichlorophenyl)furan-2-carboxylic acid
(IVg). Yield 50%, mp 237–238°C (from EtOH–DMF);
published data: mp 232–235 [15], 234–238°C [23].
5-(2-Chloro-4-nitrophenyl)furan-2-carboxylic
acid (IVh). Yield 70%, mp 257–258°C (from EtOH–
DMF); published data [24]: mp 252–254°C. Found, %:
C 49.24; H 2.30; Cl 5.15. C11H6ClNO5. Calculated, %:
C 49.37; H 2.26; N 5.23.
5-(4-Methoxy-2-nitrophenyl)furan-2-carboxylic
acid (IVi). Yield 55%, mp 184–185°C (from EtOH–
DMF); published data [25]: mp 182–184°C.
5-(4-Methyl-2-nitrophenyl)furan-2-carboxylic
acid (IVj). Yield 45%, mp 199–200°C (from EtOH–
DMF); published data [23]: mp 197–200°C.
Methyl 5-(2-fluorophenyl)furan-2-carboxylate
(Va). Yield 57%, bp 148–150°C (2 mm), mp 42–43°C
(from hexane). Found, %: C 65.26; H 4.04. C12H9FO3.
Calculated, %: C 65.46; H 4.12.
5-(2-Nitrophenyl)furan-2-carboxylic acid (IVa).
Yield 37%, mp 223–224°C (from EtOH–DMFA); pub-
lished data [14]: mp 223–224°C. 1H NMR spectrum, δ,
ppm: 6.79 d (1H, 4-H, J = 3.4 Hz), 7.19 d (1H, 3-H,
J = 3.4 Hz), 7.59 t (1H, 4′-H, J = 7.8 Hz), 7.72 t (1H,
5′-H, J = 7.8 Hz), 7.82 d (1H, 6′-H, J = 7.8 Hz), 7.89 d
(1H, 3′-H, J = 7.8 Hz). Found, %: C 56.78; H 3.15;
N 6.20. C11H7NO5. Calculated, %: C 56.66; H 3.03;
N 6.01.
Methyl 5-(3-fluorophenyl)furan-2-carboxylate
(Vb). Yield 46%, bp 151–153°C (2 mm), mp 82–83°C
(from hexane); published data [8]: mp 82°C.
Methyl 5-(4-fluorophenyl)furan-2-carboxylate
(Vc). Yield 51%, bp 148–151°C (2 mm), mp 70–71°C
(from hexane); published data [8]: mp 70°C.
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SYNTHESIS OF HETEROCYCLES FROM ARYLATION ... XVIII.
545
7.8 Hz). Mass spectrum: m/z 206 [M]+. Found, %:
C 64.27; H 3.48. C11H7FO3. Calculated, %: C 64.08;
H 3.42. M 206.18.
Methyl 5-(2-chlorophenyl)furan-2-carboxylate
(Vd). Yield 56%, bp 159–163°C (2 mm), mp 67–
68°C (from hexane); published data: mp 68°C [8],
68–69°C [14].
5-(3-Fluorophenyl)furan-2-carboxylic acid
(IVl). Yield 92%, mp 142–143°C (from EtOH); pub-
lished data [15]: mp 142–146°C.
Methyl 5-(3-chlorophenyl)furan-2-carboxylate
(Ve). Yield 41%, bp 173–176°C (2 mm), mp 77–
78°C (from hexane); published data: mp 76°C [8],
81–82°C [14].
5-(4-Fluorophenyl)furan-2-carboxylic acid
(IVm). Yield 88%, mp 198–199°C (from EtOH); pub-
lished data [23]: mp 199–202°C. Found, %: C 63.87;
H 3.34. C11H7FO3. Calculated, %: C 64.08; H 3.42.
Methyl 5-(4-chlorophenyl)furan-2-carboxylate
(Vf). Yield 45%, bp 171–175°C (2 mm), mp 130–
131°C (from hexane); published data [14]: mp 131–
132°C.
5-(2-Chlorophenyl)furan-2-carboxylic acid
(IVn). Yield 93%, mp 227–228°C (from EtOH); pub-
lished data [14]: mp 230–231°C. Found, %: C 59.19;
H 3.11. C11H7ClO3. Calculated, %: C 59.35; H 3.17.
Methyl 5-(4-bromophenyl)furan-2-carboxylate
(Vg). Yield 43%, bp 186–190°C (2 mm), mp 129–
130°C (from hexane); published data [22]: mp 128–
129°C.
5-(3-Chlorophenyl)furan-2-carboxylic acid
(IVo). Yield 89%, mp 172–173°C (from EtOH); pub-
lished data [14]: mp 170–171°C.
Methyl 5-(2-trifluoromethylphenyl)furan-2-car-
boxylate (Vh). Yield 39%, bp 159–163°C (2 mm).
Found, %: C 57.60; H 3.25. C13H9F3O3. Calculated, %:
C 57.79; H 3.36.
5-(4-Chlorophenyl)furan-2-carboxylic acid
(IVp). Yield 90%, mp 197–198°C (from EtOH); pub-
lished data [22]: mp 198–201°C. 1H NMR spectrum, δ,
ppm: 7.08 d (1H, 4-H, J = 2.9 Hz), 7.29 d (1H, 3-H,
J = 2.9 Hz), 7.46 d (2H, 3′-H, 5′-H, J = 8.8 Hz), 7.81 d
(2H, 2′-H, 6′-H, J = 8.8 Hz). Found, %: C 59.16;
H 3.14. C11H7ClO3. Calculated, %: C 59.35; H 3.17.
Methyl 5-(3-trifluoromethylphenyl)furan-2-car-
boxylate (Vi). Yield 45%, bp 155–160°C (2 mm),
mp 86–87°C (from hexane); published data [15]:
mp 89°C.
5-(4-Bromophenyl)furan-2-carboxylic acid
(IVq). Yield 87%, mp 198–199°C (from EtOH); pub-
lished data [22]: mp 198–200°C.
Methyl 5-(2-chloro-5-trifluoromethylphenyl)-
furan-2-carboxylate (Vj). Yield 44%, bp 163–167°C
(2 mm), mp 117–118°C (from EtOH). Found, %:
C 51.09; H 2.58; Cl 11.54. C13H8ClF3O3. Calculated,
%: C 51.25; H 2.65; Cl 11.64.
5-(2-Trifluoromethylphenyl)furan-2-carboxylic
acid (IVr). Yield 85%, mp 171–172°C (from EtOH).
Found, %: C 56.17; H 2.83. C12H7F3O3. Calculated, %:
C 56.26; H 2.75.
Methyl 5-(4-chloro-3-trifluoromethylphenyl)-
furan-2-carboxylate (Vk). Yield 41%, bp 180–184°C
(2 mm), mp 109–110°C (from EtOH); published data
[15]: mp 113°C. Found, %: C 51.03; H 2.55.
C13H8ClF3O3. Calculated, %: C 51.25; H 2.65.
5-(3-Trifluoromethylphenyl)furan-2-carboxylic
acid (IVs). Yield 85%, mp 203–204°C (from EtOH);
published data: mp 203–208°C [15], 208–210°C [23].
1H NMR spectrum, δ, ppm: 7.05 d (1H, 4-H, J =
3.4 Hz), 7.18 d (1H, 3-H, J = 3.4 Hz), 7.55–7.64 m
(2H, 4′-H, 5′-H), 8.00–8.07 m (2H, 2′-H, 6′-H). Mass
spectrum: m/z 256 [M]+. Found, %: C 55.94; H 2.71.
C12H7F3O3. Calculated, %: C 56.26; H 2.75. M 256.18.
5-Arylfuran-2-carboxylic acids IVk–IVu (general
procedure). A solution of 4.5 g (0.08 mol) of potassium
hydroxide in 20 ml of ethanol was added to a solution
of 0.05 mol of ester Va–Vk in 30 ml of ethanol. The
mixture was heated for 30 min under reflux, diluted
with an equal volume of water, and acidified with
dilute (1:1) hydrochloric acid. The precipitate was
filtered off, washed with water, and recrystallized from
appropriate solvent.
5-(2-Chloro-5-trifluoromethylphenyl)furan-2-
carboxylic acid (IVt). Yield 89%, mp 230–231°C
(from EtOH). Found, %: C 49.40; H 2.02; Cl 12.09.
C12H6ClF3O3. Calculated, %: C 49.59; H 2.08; Cl 12.20.
5-(4-Chloro-3-trifluoromethylphenyl)furan-2-
carboxylic acid (IVu). Yield 87%, mp 213–214°C
(from EtOH); published data [15]: mp 213–215°C.
5-(2-Fluorophenyl)furan-2-carboxylic acid
(IVk). Yield 90%, mp 179–180°C (from EtOH).
1H NMR spectrum, δ, ppm: 6.88–6.92 m (1H, 4-H),
7.15–7.22 m (2H, 3-H, C6H4), 7.26 pseudotriplet (1H,
C6H4), 7.30–7.38 m (1H, C6H4), 7.97 t (1H, C6H4, J =
5-Arylfuran-2-carbonyl chlorides VIa–VIh, VIk,
and VIm–VIt (general procedure). A mixture of
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GORAK et al.
546
5-(2-Chlorophenyl)-N-[3-(2-oxopropyl)-1,2,4-
thiadiazol-5-yl]furan-2-carboxamide (Xd). Yield
89%, mp 175–176°C (from EtOH). 1H NMR spectrum,
δ, ppm: 2.21 s (3H, CH3), 3.99 s (2H, CH2), 7.37 d
(1H, 4-H, J = 4.0 Hz), 7.41 d.t (1H, 4′-H, 4J = 1.2, 3J =
0.044 mol of acid IVa–IVh, IVk, or IVm–IVt and
3 ml of thionyl chloride in 50 ml of anhydrous benzene
was heated under reflux until it became homogeneous.
The mixture was cooled, and the precipitate was
filtered off and washed with anhydrous hexane (com-
pounds VIa–VIc and VIh); otherwise, the mixture was
evaporated, and the residue was distilled under reduced
pressure (VId–VIg, VIk, VIm–VIt).
4
3
7.6 Hz), 7.48 d.t (1H, 5′-H, J = 1.2, J = 7.6 Hz),
4
3
7.54 d.d (1H, 3′-H, J = 1.2, J = 8.0 Hz), 7.73 d
(1H, 3-H, J = 3.6 Hz), 8.31 d.d (1H, 6′-H, 4J = 1.2, 3J =
8.0 Hz), 13.63 s (1H, NH). Found, %: C 52.88; H 3.38;
N 11.68. C16H12ClN3O3S. Calculated, %: C 53.12;
H 3.34; N 11.61.
5-Aryl-N-[3-(2-oxopropyl)-1,2,4-thiadiazol-5-yl]-
furan-2-carboxamides Xa–Xk (general procedure).
Acid chloride VIb, VIc, VIe–VIh, VIn–VIp, VIr, or
VIs, 3.4 mmol, was dissolved in 10 ml of anhydrous
acetonitrile, 0.33 g (3.4 mmol) of potassium thiocy-
anate was added under stirring, the mixture was heated
for 30 min at 60°C, 0.34 g (3.4 mmol) of 5-methyl-1,2-
oxazol-3-amine (VIII) was added, and the mixture was
heated under stirring for 2 h and poured into water.
The precipitate was filtered off, washed with several
portions of water, and purified by recrystallization.
5-(3-Chlorophenyl)-N-[3-(2-oxopropyl)-1,2,4-
thiadiazol-5-yl]furan-2-carboxamide (Xe). Yield
84%, mp 169–170°C (from EtOH). 1H NMR spectrum,
δ, ppm: 2.21 s (3H, CH3), 4.05 s (2H, CH2), 7.40 d
(1H, 4-H, J = 3.6 Hz), 7.48 d (1H, 4′-H, J = 8.0 Hz),
7.53 pseudotriplet (1H, 5′-H), 7.70 d (1H, 3-H, J =
3.6 Hz), 7.99 d (1H, 6′-H, J = 7.6 Hz), 8.18 s (1H,
2′-H), 13.70 s (1H, NH). Found, %: C 53.24; H 3.22;
N 11.49. C16H12ClN3O3S. Calculated, %: C 53.12;
H 3.34; N 11.61.
5-(4-Chlorophenyl)-N-[3-(2-oxopropyl)-1,2,4-
thiadiazol-5-yl]furan-2-carboxamide (Xf). Yield
78%, mp 180–181°C (from EtOH). 1H NMR spectrum,
δ, ppm: 2.20 s (3H, CH3), 3.97 s (2H, CH2), 7.17 d
(1H, 4-H, J = 2.9 Hz), 7.37 d (2H, 3′-H, 5′-H, J =
8.8 Hz), 7.65 d (1H, 3-H, J = 2.9 Hz), 8.03 d (2H,
2′-H, 6′-H, J = 8.8 Hz), 13.54 s (1H, NH). Found, %:
C 53.27; H 3.38; N 11.75. C16H12ClN3O3S. Calculated,
%: C 53.12; H 3.34; N 11.61.
5-(3-Nitrophenyl)-N-[3-(2-oxopropyl)-1,2,4-thia-
diazol-5-yl]furan-2-carboxamide (Xa). Yield 88%,
1
mp 255–256°C (from EtOH–DMF). H NMR spec-
trum, δ, ppm: 2.17 s (3H, CH3), 3.89 s (2H, CH2),
7.16 d (1H, 4-H, J = 3.3 Hz), 7.54 d (1H, 3-H, J =
3.3 Hz), 7.61–764 m (1H, 5′-H), 8.14 d (1H, 4′-H, J =
7.5 Hz), 8.32 d (1H, 6′-H, J = 7.5 Hz), 8.92 s (1H,
2′-H), 13.49 s (1H, NH). Found, %: C 51.76; H 3.28;
N 14.94. C16H12N4O5S. Calculated, %: C 51.61;
H 3.25; N 15.05.
5-(2,4-Dichlorophenyl)-N-[3-(2-oxopropyl)-1,2,4-
thiadiazol-5-yl]furan-2-carboxamide (Xg). Yield
80%, mp 215–216°C (from EtOH–DMF). H NMR
5-(4-Nitrophenyl)-N-[3-(2-oxopropyl)-1,2,4-thia-
diazol-5-yl]furan-2-carboxamide (Xb, 1:1 complex
with DMF). Yield 85%, mp 229–230°C (from EtOH–
1
spectrum, δ, ppm: 2.20 s (3H, CH3), 4.01 s (2H, CH2),
1
DMF). H NMR spectrum, δ, ppm: 2.18 s (3H, CH3),
4
7.40 d (1H, 4-H, J = 4.0 Hz), 7.56 d.d (1H, 5′-H, J =
2.82 s and 2.95 s (3H each, DMF), 3.90 s (2H, CH2),
7.19 br.s (1H, 4-H), 7.61 d (1H, 3-H, J = 3.6 Hz),
7.90 s (1H, NCHO), 8.24 d (2H, C6H4, J = 9.0 Hz),
8.28 d (2H, C6H4, J = 9.0 Hz), 13.35 s (1H, NH).
Found, %: C 50.89; H 4.45; N 15.48. C16H12N4O5S·
C3H7NO. Calculated, %: C 51.23; H 4.30; N 15.72.
2.0, 3J = 8.8 Hz), 7.69 d (1H, 3′-H, J = 2.0 Hz), 7.72 d
(1H, 3-H, J = 4.0 Hz), 8.37 d (1H, 6′-H, J = 8.8 Hz),
13.72 s (1H, NH). Found, %: C 48.17; H 2.74;
N 10.68. C16H11Cl2N3O3S. Calculated, %: C 48.50;
H 2.80; N 10.60.
5-(2,5-Dichlorophenyl)-N-[3-(2-oxopropyl)-1,2,4-
thiadiazol-5-yl]furan-2-carboxamide (Xh). Yield
5-(2-Chloro-4-nitrophenyl)-N-[3-(2-oxopropyl)-
1,2,4-thiadiazol-5-yl]furan-2-carboxamide (Xc).
Yield 83%, mp 236–237°C (from EtOH–DMF).
1H NMR spectrum, δ, ppm: 2.18 s (3H, CH3), 3.91 s
(2H, CH2), 7.58 d (1H, furan, J = 3.6 Hz), 7.65 d (1H,
1
86%, mp 223–224°C (from EtOH–DMF). H NMR
spectrum, δ, ppm: 2.21 s (3H, CH3), 4.00 s (2H, CH2),
7.42–7.47 m (2H, 4-H, 4′-H), 7.58 d (1H, 3′-H, J =
7.5 Hz), 7.69 d (1H, 3-H, J = 3.6 Hz), 8.44 d (1H,
6′-H, J = 2.0 Hz), 13.68 s (1H, NH). Found, %:
C 48.38; H 2.67; N 10.69. C16H11Cl2N3O3S. Calculat-
ed, %: C 48.50; H 2.80; N 10.60.
4
3
furan, J = 3.6 Hz), 8.23 d.d (1H, 5′-H, J = 1.2, J =
8.5 Hz), 8.32 s (1H, 3′-H), 8.77 d (1H, 6′-H, J =
8.5 Hz), 13.49 s (1H, NH). Found, %: C 47.19; H 2.87;
N 13.69. C16H11ClN4O5S. Calculated, %: C 47.24;
H 2.73; N 13.77.
5-(3,4-Dichlorophenyl)-N-[3-(2-oxopropyl)-1,2,4-
thiadiazol-5-yl]furan-2-carboxamide (Xi). Yield
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 4 2009

SYNTHESIS OF HETEROCYCLES FROM ARYLATION ... XVIII.
547
1
87%, mp 202–203°C (from EtOH–DMF). H NMR
spectrum, δ, ppm: 2.21 s (3H, CH3), 3.99 s (2H, CH2),
7.33 d (1H, 4-H, J = 3.2 Hz), 7.63 d (1H, 3-H, J =
3.2 Hz), 7.67 d (1H, 5′-H, J = 8.8 Hz), 7.98 d.d (1H,
J = 2.4 Hz), 7.54 d (1H, 3′-H, J = 3.6 Hz), 7.65 d (1H,
4′-H, J = 3.6 Hz), 7.98 br.s (1H, 5-H), 8.22–8.33 m
(2H, 5″-H, 6″-H), 8.35 s (1H, 3″-H). Found, %:
C 53.85; H 2.30; N 11.87. C16H8ClN3O5. Calculated,
%: C 53.72; H 2.25; N 11.75.
4
3
6′-H, J = 2.0, J = 8.8 Hz), 8.33 d (1H, 2′-H, J =
2.0 Hz), 13.61 s (1H, NH). Found, %: C 48.24; H 2.73;
N 10.72. C16H11Cl2N3O3S. Calculated, %: C 48.50;
H 2.80; N 10.60.
2-[5-(4-Bromophenyl)furan-2-yl]-5-(2-furyl)-
1,3,4-oxadiazole (XIIc). Yield 79%, mp 184–185°C
1
(from EtOH–DMF). H NMR spectrum, δ, ppm:
N-[3-(2-Oxopropyl)-1,2,4-thiadiazol-5-yl]-5-(2-
6.75 d.d (1H, 4-H, J = 3.6, 1.4 Hz), 7.24 d (1H, 3′-H,
J = 3.8 Hz), 7.35 d (1H, 3-H, J = 3.6 Hz), 7.42 d (1H,
4′-H, J = 3.8 Hz), 7.62 d (2H, 3″-H, 5″-H, J = 8.6 Hz),
7.80 d (2H, 2″-H, 6″-H, J = 8.6 Hz), 7.98 d (1H, 5-H,
J = 1.4 Hz). Found, %: C 53.55; H 2.44; N 7.79.
C16H9BrN2O3. Calculated, %: C 53.81; H 2.54; N 7.84.
trifluoromethylphenyl)furan-2-carboxamide (Xj).
1
Yield 84%, mp 97–98°C (from EtOH). H NMR spec-
trum, δ, ppm: 2.20 s (3H, CH3), 3.99 s (2H, CH2),
6.98 d (1H, 4-H, J = 3.2 Hz), 7.68 pseudotriplet (1H,
4′-H), 7.75–7.85 m (2H, 3-H, 5′-H), 7.87 d (1H, 3′-H,
J = 8.0 Hz), 8.08 d (1H, 6′-H, J = 8.0 Hz), 13.58 s
(1H, NH). Found, %: C 51.40; H 3.12; N 10.74.
C17H12F3N3O3S. Calculated, %: C 51.65; H 3.06;
N 10.63.
2-(2-Furyl)-5-[5-(2-trifluoromethyl)furan-2-yl]-
1,3,4-oxadiazole (XIId). Yield 76%, mp 108–109°C
1
(from EtOH). H NMR spectrum, δ, ppm: 6.75 d.d
(1H, 4-H, J = 3.6, 1.2 Hz), 7.01 d (1H, 3′-H, J =
3.6 Hz), 7.33 d (1H, 3-H, J = 3.6 Hz), 7.46 d (1H,
4′-H, J = 3.6 Hz), 7.66 t (1H, 4″-H, J = 7.6 Hz), 7.79 t
(1H, 5″-H, J = 7.6 Hz), 7.86 d (1H, 3″-H, J = 7.6 Hz),
7.91 d (1H, 6″-H, J = 7.6 Hz), 7.98 d (1H, 5-H, J =
1.2 Hz). Found, %: C 58.71; H 2.78; N 8.01.
C17H9F3N2O3. Calculated, %: C 58.97; H 2.62; N 8.09.
N-[3-(2-Oxopropyl)-1,2,4-thiadiazol-5-yl]-5-
(3-trifluoromethylphenyl)furan-2-carboxamide
(Xk). Yield 86%, mp 233–234°C (from EtOH).
1H NMR spectrum, δ, ppm: 2.21 s (3H, CH3), 3.99 s
(2H, CH2), 7.36 d (1H, 4-H, J = 3.9 Hz), 7.65–7.73 m
(3H, 3-H, C6H4), 8.26–8.32 m (1H, C6H4), 8.35 s (1H,
2′-H), 13.60 s (1H, NH). Found, %: C 51.46; H 3.10;
N 10.50. C17H12F3N3O3S. Calculated, %: C 51.65;
H 3.06; N 10.63.
2-[5-(2-Chloro-5-trifluoromethyl)furan-2-yl]-
5-(2-furyl)-1,3,4-oxadiazole (XIIe). Yield 82%,
1
mp 169–170°C (from EtOH–DMF). H NMR spec-
2-(5-Arylfuran-2-yl)-5-(2-furyl)-1,3,4-oxadi-
azoles XIIa–XIIe (general procedure). Acid chloride
VIa, VIh, VIq, VIr, or VIt, 3.4 mmol, was dissolved
in 15 ml of anhydrous pyridine, 0.46 g (3.4 mmol) of
5-(2-furyl)-1H-tetrazole (XI) was added, and the mix-
ture was heated for 3 h on a boiling water bath. The
precipitate was filtered off, washed with several
portions of water, and recrystallized from appropriate
solvent.
trum, δ, ppm: 6.76 d.d (1H, 4-H, J = 3.6, 1.4 Hz), 7.36 d
(1H, 3-H, J = 3.6 Hz), 7.50 d (1H, 4′-H, J = 3.8 Hz),
7.51 d (1H, 3′-H, J = 3.8 Hz), 7.71 d.d (1H, 4″-H, 3J =
8.4, 4J = 1.6 Hz), 7.81 d (1H, 3″-H, J = 8.4 Hz), 7.99 d
(1H, 5-H, J = 1.4 Hz), 8.18 d (1H, 6″-H, J = 1.6 Hz).
Found, %: C 53.78; H 2.20; N 7.48. C17H8ClF3N2O3.
Calculated, %: C 53.63; H 2.12; N 7.36.
3-Substituted 6-(5-arylfuran-2-yl)[1,2,4]triazolo-
[3,4-b][1,3,4]thiadiazoles XIVa–XIVn (general
procedure). A mixture of 5 mmol of triazole XIIIa–
XIIIe, 5 mmol of acid IVa–IVc, IVg, IVm, IVn, IVp,
or IVs, and 7 ml of phosphoryl chloride was heated
under reflux until hydrogen chloride no longer evolved
and for 3 h more. The mixture was cooled and poured
onto 100 g of crushed ice, an aqueous solution of
ammonia was added to pH 8 under effective external
cooling, and the precipitate was filtered off, washed on
a filter with warm water (up to 500 ml), dried in air,
and recrystallized from appropriate solvent.
2-(2-Furyl)-5-[5-(2-nitrophenyl)furan-2-yl]-1,3,4-
oxadiazole (XIIa). Yield 73%, mp 139–140°C (from
1
EtOH–DMF). H NMR spectrum, δ, ppm: 6.75 d.d
(1H, 4-H, J = 3.6, 1.6 Hz), 7.07 d (1H, 3′-H, J =
3,8 Hz), 7.33 d (1H, 3-H, J = 3.6 Hz), 7.47 d (1H,
4′-H, J = 3.8 Hz), 7.67 pseudotriplet (1H, 4″-H),
7.80 pseudotriplet (1H, 5″-H), 7.92–7.96 m (2H, 3″-H,
6″-H), 7.98 d (1H, 5-H, J = 1.8 Hz). Found, %:
C 59.30; H 2.74; N 12.77. C16H9N3O5. Calculated, %:
C 59.45; H 2.81; N 13.00.
2-[5-(2-Chloro-4-nitrophenyl)furan-2-yl]-5-(2-
3-(2-Methylfuran-3-yl)-6-[5-(2-nitrophenyl)-
furan-2-yl][1,2,4]triazolo[3,4-b][1,3,4]thiadiazole
(XIVa). Yield 80%, mp 219–220°C (from EtOH–
furyl)-1,3,4-oxadiazole (XIIb). Yield 77%, mp 208–
1
209°C (from EtOH–DMF). H NMR spectrum, δ,
1
ppm: 6.76 pseudodoublet (1H, 4-H), 7.37 d (1H, 3-H,
DMF). H NMR spectrum, δ, ppm: 2.70 s (3H, CH3),
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 4 2009

GORAK et al.
arom, J = 7.8 Hz), 7.50 t (1H, Harom, J = 7.8 Hz), 7.55–
548
7.11 d (1H, 4-H, J = 2.0 Hz), 7.25 d (1H, 3′-H, J =
4.0 Hz), 7.65 d (1H, 4′-H, J = 4.0 Hz), 7.67–7.71 m
(2H, 5-H, 4″-H), 7.80 pseudotriplet (1H, 5″-H), 7.93–
7.98 m (2H, 3″-H, 6″-H). Found, %: C 54.30; H 2.72;
N 17.97. C18H11N5O4S. Calculated, %: C 54.96;
H 2.82; N 17.80.
H
7.62 m (4H, Harom), 7.65 d (1H, 4-H, J = 2.9 Hz),
7.91 d (1H, Harom, J = 6.8 Hz), 8.25 d (2H, Harom, J =
6.8 Hz). Found, %: C 59.97; H 2.91; N 14.87.
C19H11ClN4OS. Calculated, %: C 60.24; H 2.93;
N 14.79.
6-[5-(2-Nitrophenyl)furan-2-yl]-3-phenyl[1,2,4]-
6-[5-(2-Chlorophenyl)furan-2-yl]-3-(2-methyl-
furan-3-yl)[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole
(XIVg). Yield 70%, mp 174–175°C (from EtOH–
triazolo[3,4-b][1,3,4]thiadiazole (XIVb). Yield 85%,
1
mp 194–195°C (from EtOH–DMF). H NMR spec-
1
trum, δ, ppm: 7.33 d (1H, 3-H, J = 3.9 Hz), 7.55–
7.65 m (3H, Harom), 7.72 t (1H, Harom, J = 7.8 Hz),
7.75 d (1H, 4-H, J = 3.9 Hz), 7.84 t (1H, Harom, J =
7.8 Hz), 8.01 t (2H, Harom, J = 8.8 Hz), 8.27 d (2H,
arom, J = 7.8 Hz). Found, %: C 58.42; H 2.70;
N 17.77. C19H11N5O3S. Calculated, %: C 58.61;
H 2.85; N 17.99.
DMF). H NMR spectrum, δ, ppm: 2.67 s (3H, CH3),
7.12 br.s (1H, 4-H), 7.42 d (1H, 3′-H, J = 3.2 Hz),
7.46 t (1H, 4″-H, J = 7.6 Hz), 7.53 t (1H, 5″-H, J =
7.6 Hz), 7.63 d (1H, 3″-H, J = 8.0 Hz), 7.71 d (1H,
4′-H, J = 3.2 Hz), 7.78 br.s (1H, 5-H), 7.94 d (1H,
6″-H, J = 7.6 Hz). Found, %: C 56.68; H 2.92;
N 14.52. C18H11ClN4O2S. Calculated, %: C 56.47;
H 2.90; N 14.64.
H
3-(2-Methylfuran-3-yl)-6-[5-(3-nitrophenyl)-
furan-2-yl][1,2,4]triazolo[3,4-b][1,3,4]thiadiazole
(XIVc). Yield 77%, mp 262–263°C (from EtOH–
3-Benzyl-6-[5-(2-chlorophenyl)furan-2-yl][1,2,4]-
triazolo[3,4-b][1,3,4]thiadiazole (XIVh). Yield 74%,
1
1
DMF). H NMR spectrum, δ, ppm: 2.70 s (3H, CH3),
mp 185–186°C (from EtOH–DMF). H NMR spec-
7.20 d (1H, 4-H, J = 1.6 Hz), 7.58 d (1H, 3′-H, J =
3.8 Hz), 7.64 d (1H, 4′-H, J = 3.8 Hz), 7.69 d (1H,
5-H, J = 1.6 Hz), 7.79 t (1H, 5″-H, J = 8.0 Hz), 8.22 d
(1H, 4″-H, J = 8.0 Hz), 8.27 d (1H, 6″-H, J = 8.0 Hz),
8.60 s (1H, 2″-H). Found, %: C 54.72; H 2.88;
N 17.61. C18H11N5O4S. Calculated, %: C 54.96;
H 2.82; N 17.80.
trum, δ, ppm: 4.43 s (2H, CH2), 7.22 t (1H, Harom, J =
6.8 Hz), 7.27–7.48 m (8H, Harom, 3-H, 4-H), 7.52 d
(1H, Harom, J = 7.8 Hz), 7.94 d (1H, Harom, J = 7.8 Hz).
Found, %: C 60.78; H 3.12; N 14.02. C20H13ClN4OS.
Calculated, %: C 61.15; H 3.34; N 14.26.
6-[5-(4-Chlorophenyl)furan-2-yl]-3-propyl[1,2,4]-
triazolo[3,4-b][1,3,4]thiadiazole (XIVi). Yield 60%,
3-(2-Methylfuran-3-yl)-6-[5-(4-nitrophenyl)-
furan-2-yl][1,2,4]triazolo[3,4-b][1,3,4]thiadiazole
(XIVd). Yield 75%, mp 294–295°C (from EtOH–
1
mp 192–193°C (from EtOH–DMF). H NMR spec-
trum, δ, ppm: 1.10 t (3H, CH3, J = 7.8 Hz), 1.91–
1.97 m (2H, CH2CH3), 3.05 t (2H, 3-CH2, J = 7.8 Hz),
7.04 d (1H, 3-H, J = 3.4 Hz), 7.31 d (1H, 4-H, J =
3.4 Hz), 7.43 d (2H, 3′-H, 5′-H, J = 8.3 Hz), 7.78 d
(2H, 2′-H, 6′-H, J = 8.3 Hz). Found, %: C 55.58;
H 3.72; N 16.08. C16H13ClN4OS. Calculated, %:
C 55.73; H 3.80; N 16.25.
1
DMF). H NMR spectrum, δ, ppm: 2.71 s (3H, CH3),
7.14 br.s (1H, 4-H), 7.62 d (1H, 3′-H, J = 3.2 Hz),
7.66–7.71 m (2H, 5-H, 4′-H), 8.12 d (2H, 3″-H, 5″-H,
J = 8.4 Hz), 8.33 d (2H, 2″-H, 6″-H, J = 8.4 Hz).
Found, %: C 55.12; H 2.90; N 17.69. C18H11N5O4S.
Calculated, %: C 54.96; H 2.82; N 17.80.
6-[5-(4-Chlorophenyl)furan-2-yl]-3-(2-methyl-
furan-3-yl)[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole
(XIVj). Yield 78%, mp 263–264°C (from EtOH–
3-(2-Furyl)-6-[5-(4-nitrophenyl)furan-2-yl]-
[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole (XIVe). Yield
1
81%, mp 300–301°C (from EtOH–DMF). H NMR
1
DMF). H NMR spectrum, δ, ppm: 2.70 s (3H, CH3),
spectrum, δ, ppm: 6.78 d.d (1H, 4-H, J = 3.6, 1.4 Hz),
7.34 d (1H, 3′-H, J = 3.6 Hz), 7.64 d (1H, 3-H, J =
3.6 Hz), 7.73 d (1H, 4′-H, J = 3.6 Hz), 7.97 d (1H,
5-H, J = 1.4 Hz), 8.14 d (2H, 3″-H, 5″-H, J = 8.8 Hz),
8.35 d (2H, 2″-H, 6″-H, J = 8.8 Hz). Found, %:
C 53.61; H 2.48; N 18.53. C17H9N5O4S. Calculated, %:
C 53.83; H 2.39; N 18.46.
7.13 br.s (1H, 4-H), 7.32 d (1H, 3′-H, J = 3.2 Hz),
7.52 d (2H, 3″-H, 5″-H, J = 8.2 Hz), 7.60 d (1H, 4′-H,
J = 3.2 Hz), 7.69 br.s (1H, 5-H), 7.86 d (2H, 2″-H,
6″-H, J = 8.2 Hz). Found, %: C 56.68; H 2.82;
N 14.52. C18H11ClN4O2S. Calculated, %: C 56.47;
H 2.90; N 14.64.
6-[5-(4-Chlorophenyl)furan-2-yl]-3-(2-furyl)-
6-[5-(2-Chlorophenyl)furan-2-yl]-3-phenyl[1,2,4]-
[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole (XIVk). Yield
73%, mp 244–245°C (from EtOH–DMF). H NMR
triazolo[3,4-b][1,3,4]thiadiazole (XIVf). Yield 84%,
mp 235–236°C (from EtOH–DMF). H NMR spec-
1
1
spectrum, δ, ppm: 6.77 d.d (1H, 4-H, J = 3.6, 1.4 Hz),
trum, δ, ppm: 7.38 d (1H, 3-H, J = 2.9 Hz), 7.43 t (1H,
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7. Kort, M.E., Drizin, I., Gregg, R.J., Scanio, M.J.C.,
Shi, L., Gross, M.F., Atkinson, R.N., Johnson, M.S.,
Pacofsky, G.J., Thomas, J.B., Carroll, W.A., Kram-
bis, M.J., Liu, D., Shieh, C.-C., Zhang, X.F., Hernan-
dez, G., Mikusa, J.P., Zhong, C., Joshi, S., Honore, P.,
Roeloffs, R., Marsh, K.C., Murray, B.P., Liu, J.,
Werness, S., Faltynek, C.R., Krafte, D.S., Jarvis, M.F.,
Chapman, M.L., and Marron, B.E., J. Med. Chem.,
2008, vol. 51, p. 407.
7.31–7.34 m (2H, 3′-H, 4′-H), 7.52 d (2H, 3″-H, 5″-H,
J = 8.4 Hz), 7.64 d (1H, 3-H, J = 3.6 Hz), 7.88 d (2H,
2″-H, 6″-H, J = 8.4 Hz), 7.96 d (1H, 5-H, J = 1.4 Hz).
Found, %: C 55.07; H 2.55; N 15.32. C17H9ClN4O2S.
Calculated, %: C 55.37; H 2.46; N 15.19.
6-[5-(4-Fluorophenyl)furan-2-yl]-3-(2-furyl)-
[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole (XIVl). Yield
1
79%, mp 253–254°C (from EtOH–DMF). H NMR
8. Lee, S., Yi, K.-Y., Hwang, S.-K., Lee, B.-H., Yoo, S.-E.,
spectrum, δ, ppm: 6.77 d.d (1H, 4-H, J = 3.6, 1.2 Hz),
7.24–7.35 m (4H, 3′-H, 3″-H, 4′-H, 5″-H), 7.62 d (1H,
3-H, J = 3.6 Hz), 7.92 d.d (2H, 2″-H, 6″-H, JHH = 8.8,
and Lee, K., J. Med. Chem., 2005, vol. 48, p. 2882.
9. Pfefferkorn, J.A., Green, M.L., Nugent, R.A.,
Gross, R.J., Mitchell, M.A., Finzel, B.C., Harris, M.S.,
Wells, P.A., Shelly, J.A., Anstadt, R.A., Kilkuskie, R.E.,
Kopta, L.A., and Schwende, F.J., Bioorg. Med. Chem.
Lett., 2005, vol. 15, p. 2481.
JHF = 5.6 Hz), 7.96 d (1H, 5-H, J = 1.2 Hz). Found, %:
C 57.80; H 2.66; N 15.75. C17H9FN4O2S. Calculated,
%: C 57.95; H 2.57; N 15.90.
3-(2-Furyl)-6-[5-(3-trifluoromethyl)furan-2-yl]-
[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole (XIVm).
Yield 70%, mp 225–226°C (from EtOH–DMF).
1H NMR spectrum, δ, ppm: 6.81 br.s (1H, 4-H),
7.32 br.s (1H, 3-H), 7.55 d (1H, 3′-H, J = 3.9 Hz),
7.71 d (1H, 4′-H, J = 3.9 Hz), 7.74–7.80 m (2H, C6H4),
8.03 s (1H, 5-H), 8.12–8.16 m (2H, C6H4). Found, %:
C 55.09; H 2.03; N 13.17. C18H9F3N4O2S. Calculated,
%: C 53.73; H 2.25; N 13.92.
10. Oleinik, A.F., Vozyakova, T.I., Novitskii, K.Yu., Zyko-
va, T.N., Gus’kova, T.A., and Pershin, G.N., Khim.-
Farm. Zh., 1976, no. 4, p. 46.
11. Oleinik, A.F., Modnikova, G.A., Novitskii, K.Yu., Gus’-
kova, T.A., and Pershin, G.N., Khim.-Farm. Zh., 1974,
no. 5, p. 7; Oleinik, A.F., Novitskii, K.Yu., Vozyako-
va, T.I., Gus’kova, T.A., Pershin, G.N., and Solov’e-
va, N.P., Khim.-Farm. Zh., 1977, no. 4, p. 27; Olei-
nik, A.F., Novitskii, K.Yu., Dozorova, E.N., Solov’e-
va, N.P., Polukhina, M.M., Novitskaya, N.A., and Per-
shin, G.N., Khim.-Farm. Zh., 1980, no. 9, p. 47; Olei-
nik, A.F., Adamskaya, E.V., Okishnevich, O.V., and
Pershin, G.N., Khim.-Farm. Zh., 1983, no. 6, p. 683;
Oleinik, A.F., Vozyakova, T.I., Filitis, L.N., Okinshe-
vich, O.V., Pershin, G.N., and Shestakovskii, V.M.,
Pharm. Chem. J., 1984, vol. 18, p. 410.
3-Benzyl-6-[5-(3,4-dichlorophenyl)furan-2-yl]-
[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole (XIVn). Yield
1
79%, mp 265–266°C (from EtOH–DMF). H NMR
spectrum, δ, ppm: 4.42 s (2H, CH2), 7.22 t (1H, p-H,
C6H5, J = 7.8 Hz), 7.26–7.38 m (4H, C6H5), 7.42 d
(1H, 3-H, J = 2.9 Hz), 7.60 d (1H, C6H3, J = 7.8 Hz),
7.76 d.d (1H, C6H3, J = 8.8, 1.9 Hz), 7.90 br.s (1H,
4-H), 7.99 d (1H, C6H3, J = 1.9 Hz). Found, %:
C 55.99; H 2.85; N 12.90. C20H12Cl2N4OS. Calculated,
%: C 56.22; H 2.83; N 13.11.
12. Obushak, N.D., Lesyuk, A.I., Ganushchak, N.I., Mel’-
nik, G.M., and Zavalii, P.Yu., Zh. Org. Khim., 1986,
vol. 22, p. 2331; Pong, S.F., Pelosi, S.S., Wessels, F.L.,
Yu, C.-N., Burns, R.H., White, R.E., Anthony, D.R.,
Ellis, K.O., Wright, G.C., and White, R.L., Arzneim.-
Forsch. Drug Res. II, 1983, vol. 33, p. 1411; Dombrov-
skii, A.V., Usp. Khim., 1984, vol. 53, p. 1625; Krutoši-
kova, A., Zbořnik prac chemickotechnol. fakult. SVŠT
1979–1981, Bratislava, 1986, p. 15; Ref. Zh., Khim.,
1987, no. 6Zh218.
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