Synthesis of spiranes by cyclocondensation of 2-phenacylbenzothiazole with hydrazines and o-hydroxybenzaldehydes

Article abstract of DOI:10.1023/A:1023089212894

2-Phenacylbenzothiazole reacts with hydrazines and o-hydroxybenzaldehydes to give hydrazones and and chalcones. These compounds tend to isomerize to benzothiazole-2-spiro-3′-pyrazoles and benzo[b]pyran-2-spiro-2′-benzothiazoles, respectively.

Full text of DOI:10.1023/A:1023089212894

Chemistry of Heterocyclic Compounds, Vol. 39, No. 1, 2003
SYNTHESIS OF SPIRANES BY
CYCLOCONDENSATION OF
2-PHENACYLBENZOTHIAZOLE WITH
o
HYDRAZINES AND -HYDROXY-
BENZALDEHYDES
A. V. Vypirailenko, I. B. Dzvinchuk, and M. O. Lozinskii
2-Phenacylbenzothiazole reacts with hydrazines and o-hydroxybenzaldehydes to give hydrazones and
chalcones. These compounds tend to isomerize to benzothiazole-2-spiro-3'-pyrazoles and benzo[b]-
pyran-2-spiro-2'-benzothiazoles, respectively.
Keywords: benzopyrans, benzothiazoles, hydrazones, pyrazoles, spiranes, isomerism.
We have already shown that 2-phenacylbenzimidazole condenses with hydrazines and aldehydes in the
usual manner to give the corresponding hydrazones [1] and chalcones [2]. In a study of the analogous
transformations of 2-phenacylbenzothiazole (1), we discovered cases of isomerization caused by intramolecular
condensation at the C=N bond of the benzothiazole system, which would have been difficult to predict
theoretically.
Thus, a rather stable hydrazone 2 was obtained only in the case of p-nitrophenylhydrazine. The reaction
with hydroxyethylhydrazine led to enehydrazine 3, which exists in solution as an equilibrium mixture with
tautomeric spiran form 4. Spiran 5, which does not undergo tautomerization, was obtained with hydrazine.
Condensation with p-hydroxybenzaldehyde gave expected chalcone 6. The reaction with
salicylaldehyde does not stop at the formation of chalcone 7, but rather leads to spiran 8. This product in
solution displays tautomerism with chalcone form 7. Condensation with 3,5-dibromosalicylaldehyde gave
stable spiran 9.
1
The structures of the products were established by H NMR spectroscopy using solutions in DMSO-d6
at 300 MHz. The signals for the NH group protons of spiran forms 8 and 9 at 8.56 and 8.98 ppm and of the
phenolic hydroxyl proton of tautomer 7 and 6 at 10.29 and 10.07 ppm provide the most information in the
spectra of the products of the condensation with aldehydes. The signals of the benzoyl group protons
corresponding to structures 6-9 are characteristic: o-protons at 7.95-7.98 ppm, p-protons at 7.45-7.65 ppm, and
m-protons at 7.33-7.51 ppm. Thus, the ketol–lactol isomerism characteristic for o-hydroxystyryl ketones [3] may
be excluded. According to the integral intensities, the equilibrium solutions of 3 and 8 were found to contain 20
and 78% spiran form, respectively.
__________________________________________________________________________________________
Institute of Organic Chemistry, National Academy of Sciences of Ukraine, 02094 Kiev, Ukraine; e-mail:
avpr@i.com.ua. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 131-133, January, 2003.
Original article submitted May 8, 2002.
0009-3122/03/3901-0123$25.00©2003 Plenum Publishing Corporation
123

Ph
Ph
S
S
S
NH
NH
N
Ph
N
H
N
N
H
N
H
H
N
N
H
CH2CH2OH
4
HOCH2CH2
5
3
N2H4
HO
HO
NHNH2
HO
NHNH2
NO2
S
S
CHO
S
N
Ph
N
Ph
N
Ph
H
N
N
O
O
CHO
1
6
OH
CHO
OH
Br
Br
2
O2N
Br
Br
O
S
HO
O
S
S
N
H
N
H
N
Ph
Ph
O
O
Ph
9
O
7
8

EXPERIMENTAL
p-Nitrophenylhydrazone of 2-Phenacylbenzothiazole (2).
A
mixture of
1
(10 mmol),
p-nitrophenylhydrazine (10 mmol), and acetic acid (10 ml) was stirred at 55°C for 5 min. After cooling, the
precipitate was filtered off and washed with 2-propanol and ether to give 2 in 79% yield; mp 171-173.5°C
1
(dec.). H NMR spectrum, δ, ppm (J, Hz): 4.88 (2H, s, CH2); 7.34-8.05 (9H, m, C6H5 + 4-H, 5-H, 6-H, 7-H);
7.92, 8.18 (2×2H, 2d, J = 9.0, p-C6H4); 10.86 (1H, s, NH). Found, %: C 64.75; H 4.18; N 14.50. C21H16N4O2S.
Calculated, %: C 64.93; H 4.15; N 14.42.
2-[β-(2-Hydroxyethylhydrazino)styryl]benzothiazole (3).
A
mixture of
1
(5 mmol),
hydroxyethylhydrazine (7.5 mmol), acetic acid (0.1 ml), and 2-propanol (5 ml) was heated at reflux for 1 h.
After cooling, the precipitate was filtered off and washed with 2-propanol to give 3 in 82% yield;
1
mp 135-136°C. H NMR spectrum, δ, ppm (J, Hz): signals common for forms 3 and 4: 3.77 (2H, m, CH2N);
4.14 (2H, m, CH2O); 5.40 (1H, br. s, OH); 7.28 (1H, t, J = 7.5, p-HPh); 7.36-7.42 (2H, m, m-HPh + 4-H); signals
for form 3: 4.99 (1H, br. s, NH–CH2); 6.47 (1H, s, –CH=); 6.79, 6.97, 7.13 (3×1H, 3 m, 5-H, 7-H, 6-H); 7.66
(1H, br. s, NH–C=CH); 7.79 (2H, d, J = 7.8, o-HPh); signals for form 4: 6.59 (1H, s, –CH=); 6.72, 7.08 (3×1H,
3 m, 5-H, 7-H, 6-H); 7.60 (2H, d, J = 7.8, o-HPh); 8.11, 8.60 (2×1H, 2 br. s, 2NH). Found, %: C 65.76; H 5.52;
N 13.55. C17H17N3OS. Calculated, %: C 65.57; H 5.50; N 13.49.
2,3-Dihydrobenzothiazole-2-spiro-3'-(2',3'-dihydro-5'-phenylpyrazole)
(5)
was
obtained
1
analogously to 2. Yield of 5 99%; mp 110-115°C. Mass spectrum, m/z (Irel, %): 267 [M+] (100). H NMR
spectrum, δ, ppm (J, Hz): 6.32 (1H, s, –CH=); 6.39 (1H, m, 6-H); 6.67 (1H, m, 5-H); 7.16 (1H, d, J = 7.8, 7-H);
7.31 (1H, t, J = 6.9, p-HPh); 7.38-7.44 (3H, m, 4-H + m-HPh); 7.75 (2H, d, J = 8.4, o-HPh); 8.64 (2H, br. s, 2NH).
Found, %: C 67.20; H 4.98; N 15.75. C15H13N3S. Calculated, %: C 67.39; H 4.90; N 15.72.
2-(α-Benzoyl-4-hydroxystyryl)benzothiazole (6) was obtained in 70% yield according to our previous
1
procedure [2]; mp 186-187°C. H NMR spectrum, δ, ppm (J, Hz): 6.70, 7.29 (2×2H, 2 d, J = 8.7, p-C6H4);
7.41-7.47 (2H, m, 5-H, 6-H); 7.51 (2H, dd, J1 = J2 = 7.2, m-HPh); 7.65 (1H, t, J = 7.2, p-HPh); 7.76 (1H, s, –CH=);
7.84 (1H, m, 7-H); 7.98 (2H, d, J = 7.2, o-HPh); 8.10 (1H, m, 4-H); 10.07 (1H, br. s, OH). Found, %: C 74.10;
H 4.33; N 3.97. C22H15NO2S. Calculated, %: C 73.93; H 4.23; N 3.92.
4-Benzoyl-2H-benzo[b]pyran-2-spiro-2'-(2',3'-dihydrobenzothiazole) (8) was obtained in 70% yield
1
according to our previous procedure [2]; mp 222-223°C. H NMR spectrum, δ, ppm (J, Hz): signals of form 7:
6.61-7.16 (4H, m, C6H4O); 7.87 (1H, d, J = 7.2, 7-H); 8.08 (1H, s, –CH=); 8.10 (1H, s, J = 7.2, 4-H); 10.29 (1H,
s, OH); the remaining signals are overlapped by the signals of the predominant spirane isomer 8; signals of form
8: 6.88 (1H, d, J = 8.4, 8-H); 7.02 (1H, m, 6-H); 7.27-7.36 (4H, m, 5'-H, 6'-H + m-HPh); 7.43-7.61 (5H, m, 5-H,
7-H, 4'-H, 7'-H + p-HPh); 7.94 (2H, d, J = 9.0, o-HPh); 7.98 (1H, s, 4-H); 8.56 (1H, s, NH). Found, %: C 73.95;
H 4.25; N 3.92. C22H15NO2S. Calculated, %: C 73.93; H 4.23; N 3.92.
4-Benzoyl-6,8-dibromo-2H-dihydrobenzo[b]pyran-2-spiro-2'-(2',3'-dihydrobenzothiazole) (9) was
1
obtained in 87% yield according to our previous procedure [2]; mp 221-223°C. H NMR spectrum, δ, ppm
(J, Hz): 7.34-7.39 (4H, m, 5'-H, 6'-H+m-HPh); 7.48 (1H, t, J = 8.1, p-HPh); 7.59-7.63 (2H, m, 4'-H, 7'-H); 7.77
(1H, s, 7-H); 7.87 (1H, s, 5-H); 7.96 (2H, d, J = 8.1, o-HPh); 7.99 (1H, s, 4-H); 8.98 (1H, br. s, NH). Found, %:
C 51.21; H 2.55; N 2.68. C22H13Br2NO2S. Calculated, %: C 51.29; H 2.54; N 2.72.
REFERENCES
1.
2.
I. B. Dzvinchuk, A. V. Vypirailenko, and M. O. Lozinskii, Khim. Geterotsikl. Soedin., 1195 (2001).
I. B. Dzvinchuk, A. V. Vypirailenko, M. O. Lozinskii, and T. V. Makitruk, Ukr. Khim. Zh., 65, 111
(1999).
3.
R. E. Valter, Ring–Chain Isomerism in Organic Chemistry [in Russian], Zinatne, Riga (1978), p. 93.
125