Synthesis of 3-N,N-dialkylamino-5-(3,5,6-trichloro-1,4-benzoquinon-2-yl) thiazoline-2-thiones

Article abstract of DOI:10.1023/A:1017911520208

N,N-Dialkylhydrazides of S-(4,6,7-trichloro-2,5-dihydroxy-2,3-dihydrobenzo[b]-3-furanyl)dithiocarbonic acids have been obtained by the reaction of 3,4,6,7-tetrachloro-2,5-dihydroxy-2,3-dihydrobenzo[b]furan with N,N-dialkylhydrazinium salts of N,N-dialkylh

Full text of DOI:10.1023/A:1017911520208

Chemistry of Heterocyclic Compounds, Vol. 37, No. 11, 2001
SYNTHESIS OF 3-N,N-DIALKYLAMINO-
5-(3,5,6-TRICHLORO-1,4-BENZOQUINON-
2-YL)THIAZOLINE-2-THIONES*
J. Gulbis and R. Valters
N,N-Dialkylhydrazides of S-(4,6,7-trichloro-2,5-dihydroxy-2,3-dihydrobenzo[b]-3-furanyl)dithiocarbonic
acids have been obtained by the reaction of 3,4,6,7-tetrachloro-2,5-dihydroxy-2,3-
dihydrobenzo[b]furan with N,N-dialkylhydrazinium salts of N,N-dialkylhydrazides of dithiocarbonic
acids. Recyclization in boiling ethanol in the presence of conc. HCl with subsequent oxidation leads to
the formation of 3-N,N-dialkylamino-5-(3,5,6-trichloro-1,4-benzoquinon-2-yl)thiazoline-2-thiones. An
attempt at recyclization in boiling trifluoroacetic acid led to the formation of 3-N,N-dialkylamino-5,6,8-
trichloro-7-hydroxy-2,3,3a,8b-tetrahydrothiazolo[4,5-b]benzo[d]furane-2-thiones.
Keywords:
3-N,N-dialkylamino-5-(3,5,6-trichloro-1,4-benzoquinon-2-yl)thiazoline-2-thiones,
N,N-dialkylhydrazides
of
S-(4,6,7-trichloro-2,5-dihydroxy-2,3-dihydrobenzo[b]-2-furanyl)dithio-
carbonic acid, N,N-dialkyl hydrazinium salts of N,N-dialkylhydrazides of dithiocarbonic acid,
intramolecular charge transfer, oxidation, recyclization.
The present work is a continuation of investigations [1-5] on the synthesis of heteryl-substituted
trichloro-1,4-benzoquinones by the recyclization reaction of 3,4,6,7-tetrachloro-2,5-dihydroxy-2,3-
dihydrobenzo[b]furan (1) derivatives. In molecules of heteryl-substituted trichloro-1,4-benzoquinones an
intramolecular charge transfer is observed between the electron-donating heterocycle and the electron-
withdrawing benzoquinone fragment, which is reflected in their electronic spectra. To study this phenomenon it
seemed of interest to introduce heterocyclic systems possessing stronger electron-donating properties, such as
thiazolines, thiazolinethiones, and tetrathiafulvalenes. For this purpose we studied previously the reaction of
benzofuran 1 with the anions of N-methyl- and N-phenyldithiocarbamates [3], N,N-diethyldithiocarbamate [4],
butyl dithiocarbonate, and tert-butyl trithionate [5], and carried out a recyclization reaction of the products
obtained by nucleophilic substitution of the chlorine atom in position 3 of benzofuran 1.
The aim of the present work was the synthesis of N,N-dialkylhydrazides of S-(4,6,7-trichloro-2,5-
dihydroxy-2,3-dihydrobenzo[b]-2-furanyl)dithiocarbonic acids 3a-c by the interaction of benzofuran 1 with the
N,N-dialkylhydrazinium salts of N,N-dialkylhydrazides of dithiocarbonic acid 2a-c, the study of their
recyclization reactions, and the oxidation of the recyclization products. Freshly prepared salts 2a-c were used,
obtained by the reaction of carbon disulfide with N,N-dimethyl-, N,N-diethyl-, and
_______
* Dedicated to Professor E. Lukevics on his 65th birthday.
__________________________________________________________________________________________
Riga Technical University, Riga LV-1048, Latvia; e-mail: rvalters@latnet.lv. Translated from Khimiya
Geterotsiklicheskikh Soedinenii, No. 11, pp. 1556-1561, November, 2001. Original article submitted March 28,
2001.
1424
0009-3122/01/3711-1424$25.00©2001 Plenum Publishing Corporation

N,N-pentamethylenehydrazines. Based on previous investigations [3-5] the formation of four isomeric products
may be proposed from the recyclization or cyclization, viz. derivatives of thiazolinethione 4, dithiole 7, and
tricyclic compounds 6 and 8.
S
Cl
Cl
_
Cl
C
S
+
HO
Cl
R2NHNH2 R2NNHCSS HO
NHNR2
2a–c
OH
OH
O
O
Cl
Cl
1
Cl
3a–c
EtOH / HCl
CF3COOH
X
NR2
Cl
O
N
OH
S
H
N
S
HO
Cl
Cl
Cl
N
S
S
S
S
[O]
X
H
O
Cl
Cl
Cl
Cl
Cl
6a,b
O
OH
5a–c
4a–c
S
S
S
Cl
OH
O
NNR2
H
S
O
NNR2
HO
Cl
Cl
Cl
Cl
Cl
S
S
H
O
Cl
Cl
O
9
Cl
8
OH
7
2–4 a R = Me, b R = Et, c R2 = –(CH2)5–;
5, 6 a X = NMe2, b X = NEt2, c X = N(CH2)5, d X = Me
The nucleophilic substitution reaction proceeds readily in ethanolic solution (yields of compounds 3a-c
3
1
were 54-95%). The coupling constant J of about 3 Hz observed in the H NMR spectra of compounds 3a-c
between the protons in positions 2 and 3 of the 2,3-dihydrobenzo[b]furan ring confirms the cis configuration of
the 2,3 substituents (see [6]).
The recyclization of compounds 3a-c was carried out under various conditions. Prolonged boiling in
anhydrous toluene led to the formation of a difficultly separable mixture. The most successful proved to be
recyclization in boiling ethanol in the presence of conc. hydrochloric acid, leading to the formation of the
hydrochlorides of 3-N,N-dialkylamino-5-(3,4,6-trichloro-2,5-dihydroxyphenyl)thiazoline-2-thiones 4a-c·HCl.
Compounds 4a-c·HCl were soluble in water with difficulty, practically insoluble in nonpolar organic solvents,
and soluble in ethanol, DMF, and DMSO. Drying hydrochlorides 4a-c·HCl at 80°C in vacuum for 3 h leads to
loss of hydrogen chloride and the formation of bases 4a-c. In the 1H NMR spectra of compounds 4a-c a singlet
was observed for the 4-H proton at7.65-7.98 ppm which excludes the structure of tricyclic compounds 6 or 8. In
the spectra of the latter two doublets must be displayed in the range 6.2-7.5 ppm with 3J about 7 Hz (see [4,5]).
Oxidation of compounds 4a-c with 1,4-benzoquinone in aqueous methanol solution leads to the formation of
1
3-N,N-dialkylamino-5-(3,5,6-trichloro-1,4-benzoquinon-2-yl)thiazoline-2-thiones 5a-c. In the H NMR spectra
of compounds 5a-c a singlet was observed for the 4-H proton at 8.18-8.42 ppm (CDCl3). Two absorption bands
1425

TABLE 1. Chemical Shifts of the 4-H Proton and λmax (log ) for the Charge
ε
Transfer Band of Compounds 5a-c and of Model Compounds 5d and 9
1H NMR spectrum, 4-H,
UV spectrum, λmax (log )
ε
Compound
Literature
, ppm (CDCl3)
(EtOH)
δ
5а
5b
5с
5d
9
8.38
8.18
8.42
8.27
7.16
574 (3.62)
571 (3.68)
579 (3.72)
578 (3.50)
465 (3.06)
[3]
[5]
were present in the electronic spectra of benzoquinones 5a-c, an intense band at 334 nm, which was assigned to
the * transition in the 1,4-benzoquinone system, and a band in the visible portion of the spectrum at
π→π
571-579 nm, caused by an intramolecular charge transfer between the thiazoline and the benzoquinonoid
portions of the molecule. The chemical shifts of the 4-H protons and the λmax (log ) of the charge transfer band
ε
of compounds 5a-c and of the model compounds 5d and 9 synthesized previously are given in Table 1. It is easy
to be convinced that these data confirm the structure of compounds 5, consequently structure 4 for the
recyclization product is confirmed and structure 7 is disproved.
On attempting to recyclize compounds 3a,b in boiling trifluoroacetic acid solution, the cyclization
products 6a,b were obtained, viz. 3-N,N-dialkylamino-5,6,8-trichloro-7-hydroxy-2,3,3a,8b-tetrahydrothiazolo-
[4,5-b]benzo[d]furan-2-thiones. Two doublets were observed in their 1H NMR spectra at 5.7-5.8 and
6.8-6.9 ppm (3J = 8 Hz), which confirms the cis configuration of the 3a-H and 8b-H protons and is in agreement
with the data of the 1H NMR spectrum of the previously synthesized [3] 3-methyl derivative 6d [two doublets at
5.81 (8b-H) and 6.93 ppm (3a-H), 3J = 7 Hz, in DMSO-d6). An attempt to effect the cyclization of 4a,b 6a,b in
→
boiling trifluoro-acetic acid was unsuccessful. After boiling for 3 h the initial 4a,b were isolated from the
reaction mixture.
EXPERIMENTAL
The IR spectra were recorded on a Specord M 80 instrument for suspensions in nujol and in
hexachlorobutadiene. The electronic spectra were obtained on a Specord M 40 instrument for solutions in
1
ethanol (c = 5·10-5 M). The H NMR spectra were obtained on a Bruker WH 90/DS (90 MHz) instrument,
solvents were CDCl3 or DMSO-D6, internal standard was TMS. The homogeneity of compounds was checked
by TLC on plates with a bound layer of Silufol UV 254 silica gel, eluent was chloroform or toluene,
visualization was with UV light. 3,4,6,7-Tetrachloro-2,5-dihydroxy-2,3-dihydrobenzo[b]furan (1) was obtained
by the procedure of [6].
N,N-Dialkylhydrazinium Salts of N,N-Dialkylhydrazides of Dithiocarbonic Acid (2a-c). A solution
of the N,N-dialkylhydrazine (0.2 mol) in ether (15 ml) was slowly added dropwise with stirring and cooling
(0-10°C) to a solution of carbon disulfide (6 ml, 0.1 mol) in ether (100 ml). The cooling bath was removed and
the mixture stirred for 1 h at room temperature. The precipitated solid was removed, washed with ether, and
dried. The salt was dissolved in anhydrous dichloromethane (100 ml), the solution filtered, ether was added to
the filtrate until slight turbidity, then it was left at 0°C for 24 h. The colorless hygroscopic crystals were
separated. Yields were almost quantitative. The salts were soluble in alcohols, chloroform, and
dichloromethane, and insoluble in benzene, toluene, and ether.
General Procedure for Obtaining N,N-Dialkylhydrazides of S-(4,6,7-Trichloro-2,5-dihydroxy-2,3-
b
A solution of freshly prepared dialkylhydrazinium
dihydrobenzo[ ]furan-2-yl)dithiocarbonic Acid (3a-c).
salt 2a-c (6 mmol) in ethanol (30 ml) was added dropwise during 15-30 min with stirring and cooling (0-5°C) to
1426

a solution of benzofuran 1 (1.45 g, 5 mmol) in ethanol (30 ml). The reaction mixture was stirred at <10°C for a
further 1 h, then poured into 1% aqueous acetic acid solution (200 ml), and extracted with ether (2 × 80 ml).
The ether extracts were combined and dried over magnesium sulfate. The solution was evaporated to dryness,
the residue dissolved in chloroform (20 ml) and kept in the refrigerator for 24 h. The crystals of compound 3a-c
were separated, washed on the filter with a small quantity of chloroform, and dried in a vacuum desiccator.
b
N,N-Dimethylhydrazide of S-(4,6,7-Trichloro-2,5-dihydroxy-2,3-dihydrobenzo[ ]-3-furanyl)-
dithiocarbonic Acid (3a). Yield 95%; mp 173-175°C (decomp.). IR spectrum (thin film), , cm-1: 3470 and
ν
3380 (OH), 2965, 2870, 1602, 1510. 1H NMR spectrum (DMSO-d6), , ppm, J (Hz): 3.01 [6H, s, N(CH3)2]; 5.22
δ
(1H, d, 3J = 3.4, 3-H); 5.69 (1H, d d, 3J = 3.4, 3J = 8, 2-H); 7.52 (1H, d, 3J = 8, 2-OH); 10.01 (1H, s, NH); 10.11
(1H, s, OH). Found, %: C 34.23; H 2.70; Cl 27.89; N 7.18. C11H11Cl3N2O3S2. Calculated, %: C 33.90; H 2.85; Cl
27.29; N 7.19.
b
N,N-Diethylhydrazide
of
S-(4,6,7-Trichloro-2,5-dihydroxy-2,3-dihydrobenzo[ ]-3-furanyl)-
dithiocarbonic Acid (3b). Yield 57%; mp 139-141°C (decomp.). IR spectrum (thin film), , cm-1: 3459 and
ν
3115 (OH), 2975, 2839, 1606, 1510. 1H NMR spectrum (DMSO-d6), , ppm, J (Hz): 1.09 (6H, t, CH3); 3.33 (br
δ
signal overlapping signal of H2O, NCH2); 5.38 (1H, d, 3J = 3, 3-H); 5.78 (1H, dd, 3J = 3, 3J = 8, 2-H); 7.38 (1H,
3
d, J = 8, 2-OH); 10.0 (1H, s, NH); 10.18 (1H, s, OH). Found, %: C 37.36; H 3.45; Cl 26.31; N 6.77.
C13H15Cl3N2O3S2. Calculated, %: C 37.38; H 3.62; Cl 25.46; N 6.71.
b
N,N-Pentamethylenehydrazide
of
S-(4,6,7-Trichloro-2,5-dihydroxy-2,3-dihydrobenzo[ ]-3-
furanyl)dithiocarbonic Acid (3c). Yield 54%; mp 154-156°C (decomp.). IR spectrum (thin film), , cm-1: 3307
ν
(OH), 3039, 2947, 2855, 1576. 1H NMR spectrum (DMSO-d6), , ppm, J (Hz): 1.53 [6H, br. signal, –(CH2)3–];
δ3
3
3
3.42 (br signal overlapping signal of H2O, NCH2); 5.23 (1H, d, J = 3.4, 3-H); 5.74 (1H, dd, J = 3.4, J = 8,
3
2-H); 7.47 (1H, d, J = 8, 2-OH); 9.96 (1H, s, NH); 10.11 (1H, s, OH). Found, %: C 38.45; H 3.09; Cl 25.32;
N 5.72. C14H15Cl3N3O3S2. Calculated, %: C 39.13; H 3.52; Cl 24.75; N 6.52.
General
Procedure
for
Obtaining
3-N.N-Dialkylamino-5-(3,4,6-trichloro-2,5-
dihydroxyphenyl)thiazoline-2-thiones (4a-c). Conc. HCl (3 ml) was added to a solution of compound 3a-c
(2 mmol) in ethanol (15 ml) and the mixture was boiled for 4 h. After cooling, the solution was poured into
water (100 ml), the precipitated solid was separated, washed with water, dried at 40°C, and the hydrochlorides
4a-c·HCl were obtained. After drying in vacuum at 80°C for 3 h the bases 4a-c were obtained.
3-N,N-Dimethylamino-5-(3,4,6-trichloro-2,5-dihydroxyphenyl)thiazoline-2-thione (4a). Yield 85%;
mp 247-250°C (decomp.). IR spectrum (thin film), , cm-1: 3372 (OH), 2964, 1642, 1558. H NMR spectrum
1
ν
(DMSO-d6), , ppm: 2.87 (6H, s, NCH3); 7.98 (1H, s, 4-H); 9.98 (2H, br. signal, OH).
δ
Hydrochloride 4a·HCl. Found, %: Cl 33.92. C11H9Cl3N2O2S3·HCl. Calculated, %: Cl 34.76. After
drying at 80°C in vacuum for 3 h the mp is unchanged. Found, %: C 35.67; H 2.42; Cl 28.30; N 7.46.
C11H9Cl3N2O2S2. Calculated, %: C 35.55; H 2.44; Cl 28.62; N 7.54.
3-N,N-Diethylamino-5-(3,4,6-trichloro-2,5-dihydroxyphenyl)thiazoline-2-thione (4b). Yield 83%;
mp 188-192°C (decomp.). IR spectrum (thin film), , cm-1: 3381 (OH), 2972, 2840, 1621, 1540. H NMR
1
ν
spectrum (DMSO-d6), , ppm: 0.96 (6H, t, CH3); 3.36 (br signal overlapping signal of H2O, NCH2); 7.65 (1H, s,
δ
4-H); 9.94 (2H, br. signal, OH).
Hydrochloride 4b·HCl. Found, %: Cl 32.05. C13H13Cl3N2O2S2·HCl. Calculated, %: Cl 32.51. After
drying in vacuum at 80°C for 3 h the mp is unchanged. Found, %: C 39.95; H 3.30; Cl 26.31; N 6.67.
C13H13Cl3N2O2S2. Calculated, %: C 39.06; N 3.28; Cl 26.61; N 7.01.
5-(3,4,6-Trichloro-2,5-dihydroxyphenyl)-3-piperidinothiazoline-2-thione (4c). Yield 82%;
mp 225-228°C (decomp.). IR spectrum (thin film), , cm-1: 3324 (OH), 2960, 2873, 1631, 1522. H NMR
1
ν
spectrum (DMSO-d6), , ppm: 1.65 [6H, br. signal, (CH2)3]; 3.11 (br signal overlapping signal of H2O, NCH2);
δ
7.98 (1H, s, 4-H); 10.0 (2H, br. signal, OH).
Hydrochloride 4c·HCl. Found, %: Cl 30.83. C14H13Cl3N2O2S2·HCl. Calculated, %: 31.62. After drying
at 80°C in vacuum for 3 h the mp is unchanged. Found, %: C 40.32; H 3.14; Cl 24.65; N 6.68. C14H13Cl3N2O2S2.
Calculated, %: C 40.84; H 3.18; Cl 25.83; N 6.80.
1427

General Procedure for Obtaining 3-N,N-Dialkylamino-5-(3,5,6-trichloro-1,4-benzoquinon-2-
yl)thiazoline-2-thiones (5a-c). A solution of 1,4-benzoquinone (0.25 g) in methanol (10 ml) was added to a
solution of hydroquinone 4a-c (1 mmol) in methanol (10 ml) and the mixture stirred for 30 min. Distilled water
(5 ml) was added, the mixture was stirred for a further 30 min, the precipitate was separated, washed on the
filter with 70% aqueous methanol, and dried.
3-N,N-Dimethylamino-5-(3,5,6-trichloro-1,4-benzoquinon-2-yl)thiazoline-2-thione (5a). Yield 71%;
mp 190-192°C. UV spectrum (EtOH),
(log ): 334 (4.21), 574 (3.62). IR spectrum (thin film), , cm-1:
λmax
ε
ν
1
2967, 1668 (C=O), 1602, 1542, 1524. H NMR spectrum (CDCl3), , ppm: 3.12 (6H, s, NCH3); 8.38 (1H, s,
δ
4-H). Found, %: Cl 28.07. C11H7Cl3N2O2S2. Calculated, %: Cl 28.77.
3-N,N-Diethylamino-5-(3,5,6-trichloro-1.4-benzoquinon-2-yl)thiazoline-2-thione (5b). Yield 76%;
mp 173-175°C. UV spectrum (EtOH),
(log ): 334 (4.25), 571 (3.68). IR spectrum (thin film), , cm-1:
λmax
ε
ν
1
2971, 2840, 1676 and 1664 (C=O), 1562. H NMR spectrum (CDCl3), , ppm: 1.07 (6H, t, CH3); 3.02 (2H, br.
δ
signal, NCH2); 3.85 (2H, br. signal, NCH2); 8.18 (1H, s, 4-H). Found, %: C 39.39; H 2.56; Cl 26.07; N 6.86.
C13H11Cl3N2O2S2. Calculated, %: C 39.25; H 2.79; Cl 26.74; N 7.04.
5-(3,5,6-Trichloro-1,4-benzoquinon-2-yl)-3-piperidinothiazoline-2-thione (5c). Yield 71%;
mp 183-185°C. UV spectrum (EtOH),
(log ): 334 (4.26), 579 (3.72). IR spectrum (thin film), , cm-1:
λmax
ε
ν
1
2940, 2852, 1670 (C=O), 1606, 1548, 1528. H NMR spectrum (CDCl3), , ppm: 1.73 [6H, br. signal, (CH2)3];
δ
3.36 (4H, br. signal, NCH2); 8.42 (1H, s, 4-H). Found, %: C 40.84; H 2.59; Cl 25.20; N 6.77. C14H11Cl3N2O2S2.
Calculated, %: C 41.04; H 2.71; Cl 25.96; N 6.84.
b
d
5,6,8-Trichloro-3-N,N-dimethylamino-7-hydroxy-2,3,3a,8b-tetrahydrothiazolo[4,5- ]benzo[ ]furan-
2-thione (6a). A solution of compound 3a (1 mmol) in trifluoroacetic acid (15 ml) was boiled for 4 h. The
cooled solution was poured into cold water (100 ml), the precipitated solid was separated, washed with distilled
1
water, dried, and recrystallized from toluene. Yield 86%; mp 260-262°C (decomp.). H NMR spectrum
(DMSO-d6), , ppm, J (Hz): 2.91 (6H, s, CH3); 5.69 (1H, d, J = 8, 8b-H); 6.93 (1H, d, 3J = 8, 3a-H); 10.29 (1H,
δ
br. signal, OH). Found, %: C 35.30; H 2.20; Cl 28.37; N 7.28. C11H9Cl3N2O2S2. Calculated, %: C 35.55; H 2.44;
Cl 28.62; N 7.54.
b
d
5,6,8-Trichloro-3-N,N-diethylamino-7-hydroxy-2,3,3a,8b-tetrahydrothiazolo[4,5- ]benzo[ ]furan-2-
thione (6b) was obtained from compound 3b analogously to the previous method. Yield 94%; mp 161-163°C
(decomp.). 1H NMR spectrum (DMSO-d6), , ppm, J (Hz): 1.0 (6H, t, CH3); 3.42 (br. signal, overlapping signal
δ
3
of H2O, NCH2); 5.80 (1H, d, J = 8, 8b-H); 6.78 (1H, d, J = 8, 3a-H); 10.26 (1H, br. signal, OH). Found, %:
C 38.54; H 2.91; Cl 26.64; N 6.74. C13H13Cl3N2O2S2. Calculated, %: C 39.06; H 3.28; Cl 26.61; N 7.01.
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