Synthesis of a novel heterocyclic system: 3-Chloro-7,8-dihydro[1,4] dioxino[2″,3″:4′,5′]benzo[4,5]imidazo[1,2-c][1,2,3] thiadiazole [6]

Full text of DOI:10.1007/s10593-005-0228-y

Chemistry of Heterocyclic Compounds, Vol. 41, No. 6, 2005
SYNTHESIS OF A NOVEL HETEROCYCLIC
SYSTEM: 3-CHLORO-7,8-DIHYDRO[1,4]DIOXINO-
[2'',3'':4',5']BENZO[4,5]IMIDAZO[1,2-c][1,2,3]THIADIAZOLE
L. Labanauskas1, V. Bucinskaite1, A. Brukstus1, G. Urbelis1, and I. Sharlauskas2
Keywords: benzo[4,5]imidazo[1,2-c][1,2,3]thiadiazole, 7,8-dihydro[1,4]dioxino[2'',3'':4',5']benzo[4,5]-
imidazo[1,2-c][1,2,3]thiadiazole, thionyl chloride, condensation.
While continuing an investigation of condensed heterocycles including a benzimidazole moiety [1], by
condensation of amino alcohol 1 with thionyl chloride we synthesized 3-chloro-7,8-dihydro[1,4]dioxino-
[2'',3'':4',5']benzo[4,5]imidazo[1,2-c][1,2,3]thiadiazole (2), a representative of a previously unknown heterocyclic
system. Compound 1 was synthesized by N-amination of the starting benzimidazole 3 by hydroxylamine-O-
sulfonic acid (HASA). In the IR spectrum of thiadiazole 2, there was no vibration band from an amino group. In
the 1H NMR spectra of compounds 1 and 2, the signal from the methylene protons had the shape of a multiplet,
rather than the singlet in the 4 ppm region characteristic of the dioxinobenzimidazole 3.
O
O
O
O
N
N
N
N
OH
O
O
N
OH
Cl
SOCl2
HASA
N
H
S
N
2
NH2
1
3
The IR spectra were obtained on a Perkin–Elmer Spectrum BX II FT-IR spectrophotometer in nujol; the
NMR spectra were obtained on a Varian Unity Inova (300 MHz) in a DMSO-d6 solution, internal standard TMS.
6,7-Dihydro-1H-[1,4]dioxino[2',3':4,5]benzo[d]imidazol-2-yl methanol (3).
A
mixture of
2,3-dihydro-1,4-benzodioxin-6,7-diamine (16.6 g, 0.1 mol) and glycolic acid (8.36 g, 0.11 mol) in 4 N HCl
(200 ml) was boiled for 4 h. Then activated carbon (2 g) was added and the mixture was boiled for another
10 min, filtered, cooled, and alkalinized with concentrated NH4OH. The precipitate formed was filtered out and
washed with H2O and then recrystallized from methanol. Obtained 12.2 g (59%) of compound 3; mp 234-235°C.
IR spectrum, ν, cm-1: 3150 (NH), 3290 (OH). 1H NMR spectrum, δ, ppm (J, Hz): 4.22 (4H, s, OCH2); 4.60 (2H,
d, J = 3, CH2); 5.63 (1H, t, J = 3, OH); 6.92 (2H, br. s, ArH); 11.97 (1H, br. s, NH). Found, %: C 58.54; H 5.11;
N 13.82. C10H10N2O3. Calculated, %: C 58.25; H 4.89; N 13.59.
1-Amino-6,7-dihydro-1H-[1,4]dioxino[2',3':4,5]benzo[d]imidazol-2-ylmethanol (1). A mixture of
6,7-dihydro-1H-[1,4]dioxino[2',3':4,5]benzo[d]imidazol-2-yl methanol (0.7 g, 3.5 mmol) and potassium
hydroxide (0.8 g, 1.2 mmol) in H2O (20 ml) was heated with stirring at 50°C until a solution was obtained; then
a solution of hydroxylamine-O-sulfonic acid (1 g) in H2O (5 ml), neutralized with NaHCO3 to pH 7, was added.
__________________________________________________________________________________________
1
2
Vilnius University, Vilnius LT-03225, Lithuania; e-mail: linas.labanauskas@chf.vu.lt. Institute of
Biochemistry, Vilnius LT-08662, Lithuania. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6,
pp. 922-923, June, 2005. Original article submitted February 4, 2005.
802
0009-3122/05/4106-0802©2005 Springer Science+Business Media, Inc.

The reaction mixture was cooled with ice, keeping the temperature below 40°C. After the exothermic reaction
was complete, the mixture was heated for 30 min at 40-50°C. The precipitate formed was filtered out and
recrystallized from DMF. Obtained 0.46 g (61%) of compound 1; mp 203-204°C. IR spectrum, ν, cm-1: 3175,
3198 (NH2), 3325 (OH). 1H NMR spectrum, δ, ppm (J, Hz): 4.20-4.30 (4H, m, OCH2); 4.64 (2H, d, J = 3, CH2);
5.30 (1H, t, J = 3, OH); 5.82 (2H, s, NH2); 6.90 and 6.99 (2H, s, ArH). Found, %: C 54.24; H 4.76; N 18.88.
C10H11N3O3. Calculated, %: C 54.30; H 5.01; N 19.00.
3-Chloro-7,8-dihydro[1,4-dioxino[2'',3'':4',5']benzo[4,5]imidazo[1,2-c][1,2,3]thiadiazole (2).
A
mixture of compound 1 (0.16 g, 7 mmol) and thionyl chloride (5 ml) was boiled for 15 min and then evaporated
to dryness. The residue was dissolved in water, alkalinized with NaHCO3, and extracted with ethyl acetate. After
evaporation, the residue was fractionated chromatographically (Silica gel 60, Fluka) using a 9:1 benzene–ethyl
1
acetate mixture. Obtained 0.042 g (21%) of compound 2, decomposition temperature >180°C. H NMR
spectrum, δ, ppm: 4.36-4.45 (4H, m, OCH2); 7.37 and 7.59 (2H, s, ArH). Found, %: C 45.03; H 2.51; N 15.89.
C10H6ClN3O2S. Calculated, %: C 44.87; H 2.26; N 15.70.
REFERENCES
1.
S. Tumkevicius, L. Labanauskas, V. Bucinskaite, A. Brukstus, and G. Urbelis, Tetrahedron Lett., 44,
6635 (2003).
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