Synthesis of new biheterocycles containing a 1,4-benzodioxane fragment

Article abstract of DOI:10.1134/S1070428014030233

The reaction of 1,4-benzodioxane-2-carbonyl chloride with 5-(4-aminophenyl)-1,3,4-oxa- and -thiadiazole-2-thiols afforded new biheterocyclic compounds which were converted into the corresponding S-benzyl derivatives by treatment with benzyl chloride. 5-(4

Full text of DOI:10.1134/S1070428014030233

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2014, Vol. 50, No. 3, pp. 434–438. © Pleiades Publishing, Ltd., 2014.
Original Russian Text © A.S. Avakyan, S.O. Vartanyan, A.B. Sargsyan, E.A. Markaryan, 2014, published in Zhurnal Organicheskoi Khimii, 2014, Vol. 50,
No. 3, pp. 445–449.
Synthesis of New Biheterocycles
Containing a 1,4-Benzodioxane Fragment
A. S. Avakyan, S. O. Vartanyan, A. B. Sargsyan, and E. A. Markaryan
Mndzhoyan Institute of Fine Organic Chemistry, Scientific Technological Center of Organic and Pharmaceutical Chemistry,
National Academy of Sciences of Armenia, pr. Azatutyan 26, Yerevan, 0014 Armenia
e-mail: avagal@mail.ru
Received August 28, 2013
Abstract—The reaction of 1,4-benzodioxane-2-carbonyl chloride with 5-(4-aminophenyl)-1,3,4-oxa- and -thia-
diazole-2-thiols afforded new biheterocyclic compounds which were converted into the corresponding S-benzyl
derivatives by treatment with benzyl chloride. 5-(4-Aroylaminophenyl)-1,3,4-oxa(thia)diazole-2-thiols reacted
with 2-bromomethyl-1,4-benzodioxane to give compounds in which the 1,4-benzodioxane nucleus and five-
membered heterocycle are linked through a CH2S bridge.
DOI: 10.1134/S1070428014030233
Pharmacological properties of numerous bihetero-
cyclic compounds of both synthetic and natural origin
have long attracted researchers’ attention. A large num-
ber of compounds exhibiting α2-adrenolytic, radiopro-
tective, anti-burning, antitumor, antibacterial, antidotal,
and antitubercular activity were found among bihetero-
cycles comprising a 1,4-benzodioxane nucleus. We
previously synthesized biheterocyclic compounds in
which a 1,4-benzodioxane fragment is directly linked
to five-membered heterocycles containing two or three
heteroatoms, namely thiazole, oxadiazole, thiadiazole,
and triazole. The compound containing a thiazole ring
was found to be superior to the known drug Idazoxan
in α2-adrenolytic and antihypoxic activity [1].
to 1,3,4-oxadiazole or 1,3,4-thiadiazole ring through
an aminoaryl fragment or CH2S group.
Target compounds Ia and Ib were obtained by reac-
tion of 1,4-benzodioxane-2-carbonyl chloride (III)
with 5-(4-aminophenyl)-1,3,4-oxa- and -thiadiazole-2-
thiols IVa and IVb. Treatment of amido thiols Ia and
Ib with benzyl chloride afforded the corresponding
S-benzyl derivatives IIa and IIb (Scheme 1).
Compounds VII in which the heterocyclic frag-
ments are linked through a CH2S bridge have also at-
tracted interest. With a view to synthesize such deriva-
tives we used as starting materials various N-substi-
tuted 5-(4-aminophenyl)-1,3,4-oxa- and -thiadiazole-2-
thiols Va–Ve which were prepared from oxa(thia)di-
azoles IVa and IVb and substituted benzoyl chlorides
according to Scheme 2. Compounds Va and Vb were
also synthesized independently. For this purpose, ethyl
In continuation of studies in this line, the present
work was aimed at synthesizing new biheterocyclic
compounds containing a 1,4-benzodioxane unit linked
Scheme 1.
N
N
N
O
N
O
O
COCl
O
+
SH
X
SH
X
N
H2N
H
O
III
IVa, IVb
Ia, Ib
N
O
N
O
PhCH2Cl
Ph
S
X
N
H
O
IIa, IIb
X = O (a), S (b).
434

SYNTHESIS OF NEW BIHETEROCYCLES
435
Scheme 2.
N
O
N
COCl
IVa, IVb
+
SH
X
N
H
R
R
Va–Ve
O
CS2, KOH, Δ
Va
Vb
(1) BzCl
(2) N2H4·H2O
COOEt
NH2
O
N
H
(1) CS2, KOH
(2) H2SO4
H2N
Ph
N
H
VI
R = H, X = O (a), S (b); X = O, R = 4-MeO (c), 3-Br (d); R = 3-Br, X = S (e).
Scheme 3.
O
Br
N
O
N
O
O
S
X
N
H
R
O
VIIa–VIIe
Va–Ve
N
O
N
PhCH2Cl
Ph
S
X
N
H
R
VIIIa–VIIIe
N
N
O
O
N
N
Ph
Ph
S
O
O
N
H
N
H
IX
4-aminobenzoate was initially treated with benzoyl
chloride to obtain the corresponding amido ester, and
the latter was converted into amido hydrazide VI via
reaction with hydrazine hydrate. Hydrazide VI was
then subjected to cyclization with carbon disulfide.
The yields of compounds Va and Vb synthesized by
the two methods were almost similar.
pare their pharmacological properties with those of
1,4-benzodioxane derivatives.
The structure and purity of the newly synthesized
compounds were confirmed by physicochemical meth-
ods and thin-layer chromatography.
EXPERIMENTAL
In order to obtain target products VII, thiols Va–Ve
were initially reacted with 2-chloromethyl-1,4-benzo-
dioxane in the presence of potassium hydroxide. How-
ever, this attempt was unsuccessful. Instead of expect-
ed derivative VII, in the reaction with compound Va
we isolated ~43% of symmetric biheterocycle IX con-
taining two oxadiazole rings. We succeeded in syn-
thesizing compounds VIIa–VIIe only when more
reactive 2-bromomethyl-1,4-benzodioxane was used
(Scheme 3). By treatment with benzyl chloride amido
thiols Va–Ve were converted into the corresponding
S-benzyl derivatives VIIIa–VIIIe with a view to com-
The IR spectra were measured on a Nicolet Avatar
330 FT-IR spectrometer from samples dispersed in
1
mineral oil. The H NMR spectra were recorded on
a Varian Mercury-300 instrument from solutions in
DMSO-d6 using tetramethylsilane as internal refer-
ence. The melting points were determined on a Boetius
micro hot stage. The progress of reactions and the
purity of products were monitored by thin-layer chro-
matography on Silufol UV-254 plates using benzene–
acetone (3:1) as eluent; spots were visualized by treat-
ment with iodine vapor.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 50 No. 3 2014

AVAKYAN et al.
1,4-Benzodioxane-2-carbonyl chloride (III),
436
14.36 br.s (1H, SH). Found, %: C 54.67; H 3.42;
N 11.02. C17H13N3O3S2. Calculated, %: C 54.97;
H 3.53; N 11.31.
5-(4-aminophenyl)-1,3,4-oxadiazole-2-thiol (IVa), and
N-[4-(hydrazinocarbonyl)phenyl]benzamide (VI) were
synthesized as described in [2–4].
N-[4-(5-Sulfanyl-1,3,4-oxadiazol-2-yl)phenyl]-
benzamide (Va). Yield 68% (from IVa), 64% (from
5-(4-Aminophenyl)-1,3,4-thiadiazole-2-thiol
(IVb). A solution of 2.8 g (50 mmol) of potassium
hydroxide in 15 mL of anhydrous ethanol was slowly
added to 6.0 g (40 mmol) of 4-aminobenzohydrazide
in 10 mL of anhydrous ethanol, 0.4 g (51 mmol) of
carbon disulfide was then slowly added, and the mix-
ture was heated for 3 h at 35–40°C and left overnight.
The precipitate was filtered off, washed with anhy-
drous ethanol, dried, and added in small portions to
35 mL of concentrated sulfuric acid (d = 1.98 g/cm3)
cooled to –2 to 0°C. The mixture was stirred until it
became homogeneous (~30 min) and poured onto
200 g of finely crushed ice. The crystalline material
was filtered off, washed with ice water, dried in air,
and recrystallized from anhydrous ethanol. Yield 5.2 g
1
VI); mp 304–305°C, Rf 0.49. H NMR spectrum, δ,
ppm: 7.44–7.56 m (3H) and 7.96–8.01 m (2H) (Ph),
7.86 m and 8.03 m (2H each, C6H4), 10.32 s (1H, NH),
14.30 br.s (1H, SH). Found, %: C 60.36; H 3.44;
N 13.89. C15H11N3O2S. Calculated, %: C 60.59;
H 3.73; N 14.13.
N-[4-(5-Sulfanyl-1,3,4-thiadiazol-2-yl)phenyl]-
benzamide (Vb). Yield 60%, mp 115–117°C, Rf 0.56.
1H NMR spectrum, δ, ppm: 7.43–7.56 m (3H, C6H5),
7.65 m (2H, C6H4), 7.95–8.01 m (4H, Harom), 10.29 s
(1H, NH), 14.23 br.s (1H, SH). Found, %: C 57.16;
H 3.16; N 13.07. C15H11N3OS2. Calculated, %:
C 57.49; H 3.54; N 13.41.
4-Methoxy-N-[4-(5-sulfanyl-1,3,4-oxadiazol-
2-yl)phenyl]benzamide (Vc). Yield 64%, mp 293–
295°C, Rf 0.57. 1H NMR spectrum, δ, ppm: 3.87 s (3H,
OCH3), 6.96 m (2H, C6H4O), 7.85 m and 8.01 m (2H
each, C6H4N), 7.97 m (2H, C6H4O), 10.14 s (1H, NH),
14.29 br.s (1H, SH). Found, %: C 58.54; H 3.84;
N 12.65. C16H13N3O3S. Calculated, %: C 58.70;
H 4.00; N 12.84.
1
(62%), mp 239–240°C, Rf 0.42. H NMR spectrum, δ,
ppm: 5.44 br.s (2H, NH2), 6.60 m and 7.33 m (2H
each, C6H4), 13.96 br.s (1H, SH). Found, %: C 45.56;
H 3.11; N 19.87. C8H7N3S2. Calculated, %: C 45.91;
H 3.37; N 20.08.
Amido thiols I and V (general procedure). Acid
chloride III or substituted benzoyl chloride, 50 mmol,
was added dropwise to a mixture of 50 mmol of thiol
IVa or IVb and 3.4 g (50 mmol) of pyridine in 70 mL
of anhydrous benzene. The mixture was heated for 5 h
under reflux, cooled, washed with dilute aqueous HCl
(1:1) and water, and dried over Na2SO4. The solvent
was distilled off, and the residue was crystallized from
diethyl ether and recrystallized from ethanol.
3-Bromo-N-[4-(5-sulfanyl-1,3,4-oxadiazol-2-yl)-
phenyl]benzamide (Vd). Yield 53%, mp 272–274°C,
1
Rf 0.45. H NMR spectrum, δ, ppm: 7.40 t (1H,
C6H4Br, J = 7.6 Hz), 7.69 d.d.d (1H, C6H4Br, J = 7.9,
1.8, 1.0 Hz), 7.82 m and 7.99 m (2H each, C6H4N),
8.10 d.d.d (1H, C6H4Br, J = 7.9, 1.8, 1.0 Hz), 8.20 t
(1H, C6H4Br, J = 1.8 Hz), 10.40 s (1H, NH), 14.38 br.s
(1H, SH). Found, %: C 47.48; H 2.89; N 10.93.
C15H10BrN3O2S. Calculated, %: C 47.89; H 2.68;
N 11.17.
N-[4-(5-Sulfanyl-1,3,4-oxadiazol-2-yl)phenyl]-
1,4-benzodioxane-2-carboxamide (Ia). Yield 61%,
1
mp 123–125°C, Rf 0.58. H NMR spectrum, δ, ppm:
4.28 d.d (1H, CH2, J = 11.4, 6.9 Hz), 4.47 d.d (1H,
CH2, J = 11.4, 2.7 Hz), 4.84 d.d (1H, CH, J = 6.9,
2.7 Hz), 6.81–6.88 m (3H) and 7.00 m (1H) (C6H4O),
7.85 m and 7.89 m (2H each, C6H4), 10.17 s (1H, NH),
14.30 br.s (1H, SH). Found, %: C 54.87; H 3.39;
N 11.54. C17H13N3O4S. Calculated, %: C 54.46;
H 3.69; N 11.82.
3-Bromo-N-[4-(5-sulfanyl-1,3,4-thiadiazol-2-yl)-
phenyl]benzamide (Ve). Yield 56%, mp 246–248°C,
Rf 0.39. IR spectrum, ν, cm–1: 3278 (NH), 1655 (C=O),
1
1610 (C=Carom). H NMR spectrum, δ, ppm: 7.42 t
(1H, C6H4Br, J = 7.9 Hz), 7.66 m and 7.96 m (2H
each, C6H4N), 7.67 d.d.d (1H, C6H4Br, J = 7.9, 1.8,
1.0 Hz), 7.98 d.d.d (1H, C6H4Br, J = 7.9, 1.8, 1.0 Hz),
8.18 t (1H, C6H4Br, J = 1.8 Hz), 10.38 s (1H, NH),
14.34 br.s (1H, SH). Found, %: C 45.48; H 2.89;
N 10.53. C15H10BrN3OS2. Calculated, %: C 45.92;
H 2.57; N 10.71.
S-Benzyl derivatives II and VIII (general proce-
dure). A solution of 1.7 g (30 mmol) of potassium
hydroxide in 10 mL of water was added to 30 mmol of
N-[4-(5-Sulfanyl-1,3,4-thiadiazol-2-yl)phenyl]-
1,4-benzodioxane-2-carboxamide (Ib). Yield 57%,
1
mp 220–222°C, Rf 0.53. H NMR spectrum, δ, ppm:
4.28 d.d (1H, CH2, J = 11.4, 6.9 Hz), 4.46 d.d (1H,
CH2, J = 11.4, 2.7 Hz), 4.84 d.d (1H, CH, J = 6.9,
2.7 Hz), 6.79–6.88 m (3H) and 7.00 m (1H) (C6H4O),
7.64 m and 7.83 m (2H each, C6H4), 10.16 s (1H, NH),
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 50 No. 3 2014

SYNTHESIS OF NEW BIHETEROCYCLES
437
thiol I or V, and 3.8 g (30 mmol) of benzyl chloride
was then added. The oily product was ground at room
temperature and left overnight, and the precipitate was
filtered off, washed with water and diethyl ether, dried
in air, and recrystallized from ethanol.
C6H4N), 10.13 s (1H, NH). Found, %: C 66.39;
H 4.12; N 9.78. C23H19N3O3S. Calculated, %: C 66.17;
H 4.59; N 10.07.
N-{4-[5-(Benzylsulfanyl)-1,3,4-oxadiazol-2-yl]-
phenyl}-3-bromobenzamide (VIIId). Yield 67%,
1
N-{4-[5-(Benzylsulfanyl)-1,3,4-oxadiazol-2-yl]-
mp 139–140°C, Rf 0.60. H NMR spectrum, δ, ppm:
phenyl}-1,4-benzodioxane-2-carboxamide (IIa).
4.53 s (2H, SCH2); 7.24–7.35 m (3H), 7.40–7.48 m
(3H), 7.66–7.71 m (1H), 7.88–7.93 m (2H), 7.96–
8.03 m (3H), and 8.18 t (1H, J = 1.7 Hz) (Harom);
10.40 br.s (1H, NH). Found, %: C 56.34; H 3.87;
N 9.28. C22H16BrN3O2S. Calculated, %: C 56.66;
H 3.46; N 9.01.
1
Yield 69%, mp 164–165°C, Rf 0.62. H NMR spec-
trum, δ, ppm: 4.29 d.d (1H, OCH2, J = 11.4, 6.9 Hz),
4.47 d.d (1H, OCH2, J = 11.4, 2.3 Hz), 4.53 s (2H,
SCH2), 4.85 d.d (1H, CH, J = 6.9, 2.3 Hz), 6.79–
6.89 m (3H) and 7.00 m (1H) (C6H4O), 7.23–7.36 m
(3H) and 7.42–7.49 m (2H) (C6H5), 7.82–7.94 m (4H,
C6H4N), 10.19 s (1H, NH). Found, %: C 64.45;
H 4.12; N 9.11. C24H19N3O4S. Calculated, %: C 64.71;
H 4.30; N 9.43.
N-{4-[5-(Benzylsulfanyl)-1,3,4-thiadiazol-2-yl]-
phenyl}-3-bromobenzamide (VIIIe). Yield 65%,
1
mp 205–207°C, Rf 0.54. H NMR spectrum, δ, ppm:
4.59 s (2H, SCH2); 7.22–7.36 m (3H), 7.39–7.49 m
(3H), 7.64–7.71 m (1H), 7.78–7.86 m (2H), 7.93–
8.02 m (3H), and 8.19 br.s (1H) (Harom); 10.37 br.s
(1H, NH). Found, %: C 54.48; H 3.61; N 8.59.
C22H16BrN3OS2. Calculated, %: C 54.77; H 3.34;
N 8.71.
N-{4-[5-(Benzylsulfanyl)-1,3,4-thiadiazol-2-yl]-
phenyl}-1,4-benzodioxane-2-carboxamide (IIb).
Yield 71%, mp 167–169°C, Rf 0.64. IR spectrum, ν,
cm–1: 3348 (NH), 1670 (C=O), 1580 (C=Carom).
1H NMR spectrum, δ, ppm: 4.29 d.d (1H, OCH2, J =
11.4, 6.9 Hz), 4.47 d.d (1H, OCH2, J = 11.4, 2.7 Hz),
4.58 s (2H, SCH2), 4.85 d.d (1H, CH, J = 6.9, 2.7 Hz),
6.79–6.88 m (3H) and 7.01 m (1H) (C6H4O), 7.22–
7.35 m (3H) and 7.41–7.47 m (2H) (C6H5), 7.80 m and
7.85 m (2H each, C6H4N), 10.17 s (1H, NH). Found,
%: C 62.21; H 4.00; N 8.87. C24H19N3O3S2. Calculat-
ed, %: C 62.45; H 4.15; N 9.10.
N-(4-{5-[(1,4-Benzodioxan-2-yl)methylsulfanyl]-
1,3,4-oxadiazol-2-yl}phenyl)benzamide (VIIa).
A solution of 1.7 g (30 mmol) of potassium hydroxide
in 20 mL of ethanol was added to a solution of 8.9 g
(30 mmol) of amido thiol Va in ethanol, the mixture
was stirred for 30 min at 50–60°C, and 6.9 g
(30 mmol) of 2-bromomethyl-1,4-benzodioxane [5]
was added. The mixture was heated for 2–3 h under
reflux and left overnight. The solvent was distilled off,
the residue was crystallized from water, and the precip-
itate was filtered off, washed with water and diethyl
ether, dried in air, and recrystallized from ethanol.
N-{4-[5-(Benzylsulfanyl)-1,3,4-oxadiazol-2-yl]-
phenyl}benzamide (VIIIa). Yield 68%, mp 174–
175°C, Rf 0.61. 1H NMR spectrum, δ, ppm: 4.53 s (2H,
SCH2), 7.23–7.36 m (3H, Harom), 7.44–7.57 m (5H,
H
arom), 7.88–7.93 m (2H, C6H4), 7.97–8.05 m (4H,
arom), 10.30 s (1H, NH). Found, %: C 67.86; H 4.21;
1
H
Yield 8.0 g (61%), mp 189–190°C, Rf 0.53. H NMR
N 10.58. C22H17N3O2S. Calculated, %: C 68.20;
H 4.42; N 10.85.
spectrum, δ, ppm: 3.58 d.d (1H, SCH2, J = 14.1,
7.0 Hz), 3.66 d.d (1H, SCH2, J = 14.1, 5.3 Hz),
4.13 d.d (1H, OCH2, J = 11.5, 6.4 Hz), 4.40 d.d (1H,
OCH2, J = 11.5, 2.4 Hz), 4.61 m (1H, CH), 6.74–
6.83 m (4H, C6H4O), 7.45–7.57 m (3H) and 7.97–
8.01 m (2H) (C6H5), 7.91 m and 8.03 m (2H each,
C6H4N), 10.32 s (1H, NH). Found, %: C 64.56;
H 4.12; N 9.22. C24H19N3O4S. Calculated, %: C 64.71;
H 4.30; N 9.43.
N-{4-[5-(Benzylsulfanyl)-1,3,4-thiadiazol-2-yl]-
phenyl}benzamide (VIIIb). Yield 65%, mp 222–
225°C, Rf 0.58. 1H NMR spectrum, δ, ppm: 4.58 s (2H,
SCH2), 7.22–7.37 m (3H, Harom), 7.41–7.58 m (5H,
H
arom), 7.78–7.86 m (2H, C6H4), 7.94–8.05 m (4H,
Harom), 10.28 s (1H, NH). Found, %: C 65.27; H 4.03;
N 10.19. C22H17N3OS2. Calculated, %: C 65.48;
H 4.25; N 10.41.
Amides VIIb–VIIe were synthesized in a similar
way from thiols Vb–Ve.
N-{4-[5-(Benzylsulfanyl)-1,3,4-oxadiazol-2-yl]-
phenyl}-4-methoxybenzamide (VIIIc). Yield 62%,
N-(4-{5-[(1,4-Benzodioxan-2-yl)methylsulfanyl]-
1
mp 145–147°C, Rf 0.62. H NMR spectrum, δ, ppm:
1,3,4-thiadiazol-2-yl}phenyl)benzamide (VIIb).
1
3.88 s (3H, OCH3), 4.53 s (2H, SCH2), 6.97 m and
7.97 m (2H each, C6H4O), 7.23–7.35 m (3H) and 7.44–
7.48 m (2H) (C6H5), 7.88 m and 8.01 m (2H each,
Yield 60%, mp 114–115°C, Rf 0.56. H NMR spec-
trum, δ, ppm: 3.65 d.d (1H, SCH2, J = 14.1, 6.7 Hz),
3.72 d.d (1H, SCH2, J = 14.1, 5.6 Hz), 4.12 d.d (1H,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 50 No. 3 2014

AVAKYAN et al.
438
OCH2, J = 11.5, 6.5 Hz), 4.40 d.d (1H, OCH2, J = 11.5,
2.3 Hz), 4.61 m (1H, CH), 6.74–6.85 m (4H, C6H4O),
7.44–7.56 m (3H, C6H5), 7.82 m (2H, C6H4N), 7.97–
8.02 m (4H, Harom), 10.28 s (1H, NH). Found, %:
C 62.18; H 3.95; N 8.83. C24H19N3O3S2. Calculated,
%: C 62.45; H 4.15; N 9.10.
6.76–6.83 m (4H, C6H4O), 7.41 t (1H, 5-H in C6H4Br,
J = 7.9 Hz), 7.65–7.70 m (1H, C6H4Br), 7.81–7.86 m
and 7.96–8.01 m (2H each, C6H4N), 7.95–7.99 m
(1H, C6H4Br), 8.19 t (1H, 2-H in C6H4Br, J = 1.8 Hz),
10.39 s (1H, NH). Found, %: C 54.63; H 3.47; N 8.99.
C22H16BrN3OS2. Calculated, %: C 54.77; H 3.34;
N 8.71.
N-(4-{5-[(1,4-Benzodioxan-2-yl)methylsulfanyl]-
1,3,4-oxadiazol-2-yl}phenyl)-4-methoxybenzamide
N,N′-{4,4′-[5,5′-Sulfanediyl(1,3,4-oxadiazole-5,2-
diyl)]bis(benzene-4,1-diyl)}dibenzamide (IX). Yield
1
(VIIc). Yield 65%, mp 172–174°C, Rf 0.55. H NMR
1
spectrum, δ, ppm: 3.57 d.d (1H, SCH2, J = 14.1,
7.0 Hz), 3.66 d.d (1H, SCH2, J = 14.1, 5.3 Hz), 3.87 s
(3H, OCH3), 4.13 d.d (1H, OCH2, J = 11.4, 6.3 Hz),
4.40 d.d (1H, OCH2, J = 11.4, 2.3 Hz), 4.60 m (1H,
CH), 6.73–6.82 m (4H, C6H4O2), 6.97 m (2H, C6H4O),
7.89 m and 8.01 m (2H each, C6H4N), 7.97 m (2H,
C6H4O), 10.15 s (1H, NH). Found, %: C 62.89;
H 4.12; N 8.56. C25H21N3O5S. Calculated, %: C 63.15;
H 4.45; N 8.84.
43%, mp 304–305°C. H NMR spectrum, δ, ppm:
7.43–7.55 m (6H, m-H, p-H in C6H5), 7.78–7.83 m and
7.87–7.92 m (4H each, C6H4), 7.97–8.02 m (4H, o-H
in C6H5), 10.20 s (2H, NH). Calculated, %: C 64.53;
H 3.12; N 14.78. C30H20N6O4S. Found, %: C 64.28;
H 3.60; N 14.99.
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N-(4-{5-[(1,4-Benzodioxan-2-yl)methylsulfanyl]-
1,3,4-oxadiazol-2-yl}phenyl)-3-bromobenzamide
1
(VIId). Yield 63%, mp 160–163°C, Rf 0.54. H NMR
spectrum, δ, ppm: 3.58 d.d (1H, SCH2, J = 14.1,
7.0 Hz), 3.66 d.d (1H, SCH2, J = 14.1, 5.4 Hz),
4.13 d.d (1H, OCH2, J = 11.5, 6.4 Hz), 4.40 d.d (1H,
OCH2, J = 11.5, 2.2 Hz), 4.61 m (1H, CH), 6.73–
6.83 m (4H, C6H4O), 7.43 t (1H, C6H4Br, J = 7.9 Hz),
7.67 d.d.d (1H, C6H4Br, J = 7.9, 1.7, 0.9 Hz),
7.98 d.d.d (1H, C6H4Br, J = 7.9, 1.7, 0.9 Hz), 8.19 t
(1H, C6H4Br, J = 1.7 Hz), 7.92 m and 8.01 m (2H
each, C6H4N), 10.42 s (1H, NH). Found, %: C 54.73;
H 3.23; N 7.85. C24H18BrN3O4S. Calculated, %:
C 54.97; H 3.46; N 8.01.
2. Koo, J., Avakian, S., and Martin, G., J. Am. Chem. Soc.,
N-(4-{5-[(1,4-Benzodioxan-2-yl)methylsulfanyl]-
1955, vol. 77, p. 5373.
1,3,4-thiadiazol-2-yl}phenyl)-3-bromobenzamide
3. Daoud, K.M. and Eisa, M.A.A., Iraqi Natl. J. Chem.,
1
(VIIe). Yield 55%, mp 180–182°C, Rf 0.50. H NMR
2005, no. 19, p. 405.
spectrum, δ, ppm: 3.67 d.d (1H, SCH2, J = 13.9,
6.8 Hz), 3.72 d.d (1H, SCH2, J = 13.9, 5.7 Hz),
4.13 d.d (1H, OCH2, J = 11.5, 6.4 Hz), 4.41 d.d (1H,
OCH2, J = 11.5, 2.0 Hz), 4.57–4.64 m (1H, OCH),
4. Hassan, H.M., J. Serbian Chem. Soc., 1998, vol. 63,
p. 117.
5. Koo, J. and Leonard, F., US Patent no. 3149108, 1964;
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