Synthesis and tuberculostatic activity of methyl 3-isonicotinoyl-dithiocarbazate and S,S′-dimethyl dithiocarbonate isonicotinoylhydrazone, and their reactions with amines and hydrazines

Article abstract of DOI:10.1023/A:1020681604052

Methyl 3-isonicotinoyldithiocarbazates and S,S′-dimethyl dithiocarbonate isonicotinoylhydrazone were prepared. Their reactions with primary and secondary amines, diamines, and hydrazines were studied. The newly obtained derivatives did not show tuberculostatic activity in vitro.

Full text of DOI:10.1023/A:1020681604052

Chemistry of Heterocyclic Compounds, Vol. 38, No. 7, 2002
SYNTHESIS AND TUBERCULOSTATIC
ACTIVITY OF METHYL 3-ISONICOTINOYL-
DITHIOCARBAZATE AND S,S'-DIMETHYL
DITHIOCARBONATE ISONICOTINOYLHYDRAZONE,
AND THEIR REACTIONS WITH AMINES AND HYDRAZINES
H. Foks1, J. Mieczkowska1, M. Janowiec2, Z. Zwolska2, and Z. Andrzejczyk2
Methyl 3-isonicotinoyldithiocarbazates and S,S'-dimethyl dithiocarbonate isonicotinoylhydrazone were
prepared. Their reactions with primary and secondary amines, diamines, and hydrazines were studied.
The newly obtained derivatives did not show tuberculostatic activity in vitro.
Keywords: 1,3-diazacycloalkanes, 1,2-diaziridine, S,S'-dimethyl dithiocarbonates, 1,3-dithiolane,
isonicotinehydrazide, S-methyl dithiocarbazates, 1,2,4-triazoles, tuberculostatic activity.
Among the papers on synthesis and reactivity of 3-acyldithiocarbazates, Hoggart's report describing
preparation of the compounds by reaction of carbon disulfide with phenylhydrazides in ethanolic potassium
hydroxide still seems to be the most important one [1]. It was shown that reaction of 3-acyldithiocarbazates with
hydrazine gave derivatives of 4-amino-5-methylthio-3-phenyl-1,2,4-triazole, while heated in pyridine they were
transformed into 5-mercapto-2-phenyl-1,3,4-oxadiazoles. Mechanisms of the cyclizations were presented by
Young and Wood, who also found that in concentrated sulfuric acid 3-acyldithiocarbazates were transformed
into 2-substituted 5-methylthio-1,3,4-thiadiazoles [2]. Analogous reactions were performed with methyl-3-
nicotinoyl derivative by Yoshida [3]. A considerable number of alkyl esters of 2-, 3-, and 4-pyridylthiocarbazoic
acids were obtained by Kubota who studied the influence of the compounds on respiratory function of
mitochondria [4]. The highest activity was found for derivatives possessing bulky alkyl residues, and QSAR
analysis showed a good correlation of the activity with Hansch's hydrophobic constant II [5]. Possible
applications of isonicotinoyldithiocarbazoic acid esters as rubber vulcanization accelerators, insecticides,
fungicides, therapeutics, and components of light-sensitive emulsions were indicated in related patents [6, 7].
In the paper mentioned above Kubota described picolyl and isonicotinoyl derivatives of S,S'-dimethyl
dithiocarbonate, formed as by-products during synthesis of the related monoesters [4]. Similar phenyl
derivatives were obtained by Ruefenacht by methylation of methyl 3-benzoyldithiocarbazate with methyl iodide
or dimethylsulfate [8]. The chemical properties of the dithiocarbonates have not been described yet, except our
reports on the reactivity of S,S'-dialkyl dithiocarbonate pyrazinoylbenzoylhydrazones and their tuberculostatic
activity [9, 10].
__________________________________________________________________________________________
1
Department of Organic Chemistry, Medical University of Gdansk, 80-416 Gdansk, Poland; e-mail:
2
hfoks@farmacja.amg.gda.pl. Department of Microbiology, Institute of Tuberculosis Pulmonary Diseases
01-138 Warszawa, Poland. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 918-925, July,
2002. Original article submitted January 14, 2002.
810
0009-3122/02/3807-0810$27.00©2002 Plenum Publishing Corporation

The synthesis of 3-isonicotinoyldithiocarbazate (1) is known and described in two papers [4, 7]. The
compound was obtained by reaction of isonicotinehydrazide with carbon disulfide and methyl iodide in ethanol
in the presence of potassium hydroxide. It was found that the yield of the reaction was unsatisfactory, and the
process was modified by replacing the potassium hydroxide with triethylamine.
The thioester 1 was obtained in 70% yield and reacted with morpholine and ethanolamine. Products of
the reaction with morpholine depended on the reaction conditions. Reaction of equimolar amounts of the
reagents in ethanolic solution gave, despite the temperature, the salt 2 only, which after acidification was
transformed back into the starting compound. However, prolonged reflux with an excess of morpholine gave
5-(pyridin-4-yl)-1,3,4-oxadiazole-2-thiol (3). Direct heating of the compound 1 with morpholine for 5 min gave
a morpholine derivative of the thiosemicarbazide 4, while after 2 h of heating 2-morpholino-5-(pyridin-4-yl)-
1,3,4-oxadiazole (5) was isolated. Reaction of the compound 1 with ethanolamine gave a good yield of
4-(2-hydroxyethyl)-5-(pyridin-4-yl)-1,3,4-triazole-2(3H)-thione (6).
Subsequently, the synthesis and reactivity of S,S'-dimethyl dithiocarbonate isonicotinoylhydrazone were
studied. The compound was isolated earlier as a side product in synthesis of the monoester 1 [4]. To increase the
yield of the diester, the amounts of potassium hydroxide and methyl iodide were doubled and, as a result, the
S,S'-dimethyl dithioester of the methylpyridinium salt 7 was formed as the main product. The compound 7
became a sole product when the ratio of hydrazide : carbon disulfide : base (KOH or TEA) : methyl iodide was
1 : 1 : 2 : 3, respectively. The use of potassium hydroxide was advantageous, as with TEA the obtained product
was sometimes contaminated with triethylamine hydroiodide. The prepared diester 7 was reacted with several
amines, including morpholine, 4-phenylpiperazine, n-propylamine, aniline, p-chloroaniline, ethanolamine,
alkyldiamines, hydrazine, methylhydrazine, and dimethylhydrazine.
Heating of the S,S'-dithioester 7 with morpholine, phenylpiperazine, or propylamine resulted in
cyclization to 2-amino-substituted 1,3,4-oxadiazoles 8-10. The structure of the compound 9 was confirmed by
transformation of the earlier obtained oxadiazole 5 into pyridinium methiodide.
Different results were observed for reactions of the diester with aniline or p-chloroaniline. Analysis of
the NMR, IR, and MS spectra proved that in these cases products 11 and 12 were formed as a result of
replacement of one of the S-methyl group by amine.
The reaction of the diester 7 with ethanolamine gave 3-(β-hydroxyethylamino)-4-(β-hydroxyethyl)-
substituted 1,2,4-triazole 13. The product 6 treated with an excess of methyl iodide in basic medium was
transformed into methylthio derivative 14.
Short heating (approximately 10 min.) of the diester 7 with alkylenediamines in ethanol gave crystalline
derivatives of N'-(1,3-diazacycloalkane-2-ylidene)isonicotinehydrazides 15-18. 4-Amino-2-hydrazino-1,2,4-
triazole 19 was formed by heating with 100% hydrazine hydrate in ethanol. The methylhydrazine reacted with
the diester 7 to give compound 20 containing a diaziridinylidene group. Under analogous conditions
dimethylhydrazine did not react.
The diester 7 was isolated only as its pyridinium salt, while an attempted synthesis of a cyclic diester 21
by reaction with ethylene bromide gave a 1,3-dithiolane derivative, in which the pyridinium nitrogen was not
quaternized.
The compounds 7-20 were examined for their tuberculostatic activity towards Mycobaterium
tuberculosis H37Rv strain and two "wild" strains isolated from tuberculotic patients: one resistant to
p-aminosalicylic acid (PAS), isonicotinic acid hydrazide (INH), ethambutol (ETB), and rifampicine (RFP),
another fully susceptible to the drugs administered.
In vitro investigations were performed by a classical test tube method of successive dilutions with
Youman's liquid medium containing 10% of bovine serum [11].
The determined minimum concentrations inhibiting the growth of tuberculous strains (MIC) for most of
the compounds examined were within the limits 250-1000 µg/ml, which showed that the newly obtained
811

R
H
N
N
N
N
N
+
_
+
_
+
_
n
Me
N
Me
N
6
C
N
H
N
Me
N
X
N
R
N
S
Me
I
I
N
H
k
I
O
15–18
CH2CH2OH
R1
13, 19
14
l-13, m-19
S
Me
+
_
+
g
h
C
N
H
N
C(SMe)2
C
O
N
H
N
C
N
C
O
NH NH2
Me
N
Me
N
_
N
R
I
I
H
O
7
o
11, 12
S
S
a
N
NH N
C
O
h
j
21
N
N
N
N
+
c-3, e-5, f-6
i-8
N
N
C
O
NH
N
H
C
S
S
Me
N
Me
N
_
O
R
X
N
R
O
I
S
+
d
1
3, 5, 6
8–10
b
H
N
H
_
+
+
_
C
O
NH
N
C
S
O
N
x
H2N
C
N
H
N
Me
N
C
NH
N
H
C
S
N Me
I
O
Me
O
20
2
4
3
5
6
8
9
10
11
12
13
15
16
17
18
19
X
R
O
SH
—
O
N(CH2)2OH
—
—
—
—
H
—
Cl
—
—
H
—
CH2
H
CMe2
H
N
Ph
O
O
N
N
N
SH
—
NH(CH2)2Me
—
NH(CH2)2OH
(CH2)2OH
Me
—
NHNH2
NH2
R'
—
—
—
—
—
—
—
a) CS2, EtOH, Et3N, MeI; b) EtOH, morpholine; c) EtOH, 1:2,5 morpholine, boiling, H+; d) morpholine, boiling, 5 min., H+ ; e) morpholine, boiling; f) H2NCH2CH2OH, H+;
g) CS2, EtOH, 2KOH, 3MeI; h) EtOH, amines, boiling; i) MeI; j) EtOH, MeHNNH2; k) EtOH, H2N–CHR–X–CH2–NH2; l) EtOH, H2NCH2CH2OH; m) EtOH, H2NNH2·H2O;
n) EtOH, KOH, MeI; o) CS2, EtOH, 2KOH, BrCH2CH2Br

TABLE 1.Characteristics of the Newly Synthesized Compounds
Found, %
mp, °C
——————
Com-
Empirical
formula
IR, cm-1
7
1H NMR, , ppm, DMSO-d *
δ
Yield, %
(solvent for
crystallization)
Calculated, %
6
pound
C
4
H
5
N
6
1
2
3
8
9
147-149
C11H18N4O2S2
43.72
43.69
6.22
5.99
18.50 3083, 2912, 2720, 2472, 1643,
2.72 (3H, s, Me); 3.52, 4.12 (8H, 2m, morpholine);
8.1, 9.13 (4H, 2m, pyridine); 8.5 (2H, br. s, H2N+)
95
2
18.52
(EtOH/Et2O)
1515, 1440, 1232, 1055, 980,
880, 664
218-219
(H2O)
C9H10N4OS
48.41
48.63
4.63
4.53
25.15 3312, 1615, 1560, 1440, 1344,
3.74, 4.13 (4H, 2t, 2CH2); 3.96 (1H, br. s, OH);
7.83, 8.76 (4H, 2d, pyridine)
70
6
25.20
1295, 1232, 1184, 1072, 1003,
923, 864, 720
173-176
(MeOH)
C10H14IN3OS2
C12H15IN4O2
31.26
31.34
3.55
3.68
10.78 3375, 2352, 2992, 1680, 1520,
2.92 (6H, s, 2MeS); 4.85 (3H, s, MeN+);
8.85, 9.67 (4H, 2d, pyridine)
90
7
8
10.96
1483, 1263, 1135, 1092, 843
280-284
38.67
4.26
14.78 2992, 1603, 1444, 1372, 1280,
3.9 (8H, m, morpholine); 4.6 (3H, s, MeN+);
8.75, 9.37 (4H, 2d, pyridine)
38 (h)
80 (i)
38.52
4.04
14.97
(MeOH)
1184, 1135, 1072, 1024, 975,
912, 843, 730
230-232
(MeOH)
C18H20IN5O
C11H15IN4O
48.30
48.12
4.63
4.49
15.72 2992, 1600, 1500, 1280, 1232,
3.55, 4.12 (8H, 2m, 4CH2); 4.62 (3H, s, MeN+);
7.35 (5H, m, phenyl); 8.77, 9.35 (4H, 2d, pyridine)
37
38
9
15.59
1072, 975, 843
240-243
38.36
4.46
16.28 3440, 3152, 1632, 1504, 1375,
1.1 (3H, t, CH3); 1.87 (2H, m, CH2);
3.60 (2H, m, N–CH2); 4.65 (3H, s, MeN+);
8.65, 9.38 (4H, 2d, pyridine)
10
38.17
4.37
16.18
(MeOH)
1104, 1072, 1040, 815, 672
133-135
(MeOH)
C15H17IN4OS
42.21
42.05
4.18
4.00
13.31 3403, 3003, 1640, 1483, 1472,
13.08
2.9 (3H, s, MeS); 4.52 (3H, s, MeN+);
51
43
11
12
1455, 1370, 1083, 843, 720
7.9 (5H, s, phenyl); 8.1, 9.2 (4H, 2d, pyridine)
235-237
C15H16ClIN4OS
38.72
3.36
12.02 3440, 2992, 1632, 1535, 1483,
2.97 (3H, s, MeS); 4.55 (3H, s, MeN+);
38.93
3.48
12.10
(MeOH)
1440, 1312, 992, 784, 704, 592
7.97 (4H, s, phenyl); 8.17, 9.25 (4H, 2s, pyridine)

TABLE 1 (continued)
1
2
3
4
5
6
7
8
9
193-195
(MeOH)
C12H18IN5O2
36.72
36.84
4.43
4.63
18.11 3203, 1632, 1535, 1440, 1350,
17.90
3.35, 3.60 (8H, 2m, 4CH2); 4.32 (3H, s, MeN+);
5.4 (2H, br. s, 2OH); 7.58 (1H, br. s, NH);
8.46, 8.88 (4H, 2d, pyridine)
53
13
14
1232, 1104, 1055, 750, 632
178-179
(MeOH)
C11H15IN4OS
34.98
34.93
4.20
3.99
14.96 3360, 1632, 1563, 1504, 1440,
14.81
3.05 (3H, s, MeS); 4.0, 4.55 (4H, 2s, 2CH2);
4.25 (1H, s, OH); 4.72 (3H, s, MeN+);
8.9, 9.5 (4H, 2d, pyridine)
80
1375, 1280, 1184, 1043, 843
15*2
16
274-276
(EtOH)
C10H14IN5O
C11H16IN5O
C11H16IN5O
34.69
34.60
4.25
4.06
20.32 3163, 2944, 1600, 1520, 1463,
20.17
3.85 (4H, s, 2CH2); 4.5 (3H, s, MeN+);
8.7, 9.14 (4H, 2d, pyridine)
15
14
12
1083, 704, 658
260-262
36.72
4.63
19.54 3280, 1680, 1632, 1563, 1483,
1.47 (3H, d, Me); 3.4 (1H, m, CH); 4.0 (2H, m, CH2);
(MeOH)
1312, 1152, 864, 755, 675
4.5 (3H, s, MeN+); 8.67, 9.12 (4H, 2d, pyridine)
36.58
4.46
19.39
252-255
(MeOH)
36.68
36.58
4.31
4.46
19.42 3440, 3264, 1660, 1584, 1552,
2.07 (2H, m, CH2); 3.55 (4H, m, 2CH2);
4.67 (3H, s, MeN+); 8.7 (2H, s, 2NH);
8.77, 9.52 (4H, 2d, pyridine); 10.2 (1H, s, NH)
17
19.39
1360, 1264, 1215, 1152, 1072,
843, 752, 672
273-275
(MeOH)
C13H20IN5O
C8H12IN7
40.28
40.11
5.36
5.18
18.17 3200, 1632, 1552, 1504, 1295,
1.1 (6H, s, 2Me); 3.22 (4H, s, 2CH2);
30
60
45
18
17.99
1163, 672
4.52 (3H, s, MeN+); 8.73, 9.15 (4H, 2d, pyridine)
212-213
28.98
3.84
29.72 3283, 1680, 1623, 1563, 1504,
3.75 (3H, br. s, 3NH); 4.55 (3H, s, MeN+);
19
28.84
3.63
29.43
(MeOH)
1344, 1152, 1080, 752
4.9 (2H, br. s, NH2); 8.7, 9.5 (4H, 2d, pyridine)
20*3
228-229
(MeOH)
C9H12IN5O
32.63
32.45
3.81
3.63
21.23 3415, 3003, 1683, 1632, 1563,
3.5 (3H, s, MeN+); 4.6 (3H, s, MeN+);
8.7, 9.35 (4H, 2d, pyridine)
21.02
1504, 1472, 1424, 1184, 1024,
895
203-205
(MeOH)
C9H9N3OS2
45.06
45.17
3.51
3.79
17.67 3175, 1643, 1535, 1320, 1284,
3.87 (4H, s, 2CH2); 7.95, 9.0 (4H, 2d, pyridine);
12.55 (1H, s, NH)
60
21
17.56
1040, 975, 832, 683
_______
* 17 in DMSO-d6 + TFA.
*2 MS, m/z (I, %): [M+1] – 219 (4.5), 205 (24.5), 142 (100), 127 (62.3), 98 (30.1).
*3 MS, m/z (I, %): [M+1] – 205 (7.5), 191 (43.5), 142 (100), 127 (82.2), 78 (93.1).

derivatives were not active in vitro. Isonicotinic acid hydrazide (INH) transformation into these derivatives led
to a significant decrease in biological activity. MIC of the most active compound 22 was 12.5 µg/ml for H37Rv
strain and 25 µg/ml for another strains.
EXPERIMENTAL
Melting points were determined with a Boetius apparatus and are uncorrected. The IR spectra were
recorded on a Specord IR-75 spectrophotometer. The 1H NMR spectra were determined on a Tesla Spectrometer
BS-487C, 80 MHz, and the mass spectra with a Varian MAT 711 apparatus, at an electron beam energy of 70 eV.
The results of elemental analyses (% C, H, N) for all the compounds obtained were in good agreement with the
data calculated. Reaction yields and the physical constants of the compounds obtained are given in Table 1.
Methyl 3-isonicotinoyldithiocarbazate (1). To a suspension of isonicotinhydrazide (6.85 g, 50 mmol)
in ethanol (15 ml), triethylamine (5.0 g, 50 mmol) was added, and then, through a reflux condenser, CS2 (3.8 g,
50 mmol) was introduced dropwise. The reaction mixture was stirred until homogenization, and then methyl
iodide (7.1 g, 50 mmol) was added dropwise. After 30 min 150 ml of water was added, the mixture was
ice-cooled and the precipitate of ester 1 filtered off. The reaction yielded 9.5 g (83%) of 1. After
recrystallization from MeOH mp 249-252°C (decomp.), at ca. 190°C change of crystallographic system in
accordance with Ref [4].
Methyl Ester 1 Morpholine Salt (2). Compound 1 (2.27 g, 10 mmol), ethanol (10 ml), and morpholine
(0.9 g, 10 mmol) were refluxed for 15 min and allowed to stand. The product was precipitated with anhydrous diethyl
ether. The precipitate of salt 2 on dissolving in water and acidifying with acetic acid gave the compound 1 back.
5-(Pyridin-4-yl)-1,3,4-oxadiazole-2-(3H)-thione (3). Compound 1 (2.27 g, 10 mmol) and (2 ml)
morpholine dissolved in ethanol (10 ml) were refluxed for 4 h. The solvent was distilled off, then 5 ml of water
was added and the mixture acidified with acetic acid. The precipitate was collected and recrystallized. Its mp
and IR spectrum was as in Ref [3].
N'-Morpholinocarbothio-N-isonicotinoylhydrazine (4). Compound 1 (10 mmol) and morpholine
(2 ml) were refluxed for 5 min. On cooling down 10 ml of water was added and the mixture acidified with acetic
acid. The precipitate was collected and purified by recrystallization from ethanol. Its mp and IR spectrum was as
in Ref [10].
2-Morpholino-5-(pyridin-4-yl)-1,3,4-oxadiazole (5). Compound 1 (10 mmol) and morpholine (2 ml)
were refluxed for 2 h. On cooling down, water (20 ml) was added. The mixture was extracted with chloroform,
the extract dried (MgSO4), concentrated and the precipitate purified by recrystallization. Physical constants
were as in Ref. [11].
4-(2-Hydroxyethyl)-5-(pyridin-4-yl)-1,2,4-triazole (6). Compound 1 (10 mmol) and ethanolamine (3
ml, 50 mmol) were refluxed for 1 h. On cooling down, water (10 ml) and acetic acid (3.5 ml) were added. The
mixture was ice-cooled, and the precipitate collected and recrystallized.
S,S'-Dimethyl Dithiocarbonate Isonicotinoylhydrazone Methiodide (7). To a suspension of
isonicotinhydrazide (6.85 g, 50 mmol) in ethanol (15 ml) a solution of KOH (5.6 g, 100 mmol) in EtOH (20 ml)
was added, then, through the reflux condenser, CS2 (3.8 g, 50 mmol) was added portionwise. When the mixture
became homogeneous, it was cooled down with water and MeI (21.3 g, 150 mmol) was added dropwise. After
24 h the precipitate of KI was filtered off. To the filtrate 150 ml of anhydrous Et2O was added and the
precipitate filtered off; mp after crystallization from MeOH: 173-176°C. Reaction yielded 17 g (90%) of
dithioester 7.
2-Morpholino-, 2-(4-Phenylpiperazino)- and 2-Propylamino-5-(pyridin-4-yl)-1,3,4-oxadiazole
Methiodides (8-10). To a solution of dithioester 7 (1.2 g, 50 mmol) in 5 ml EtOH, 50 mmol of appropriate
amine was added and refluxed for 2 h. Upon cooling down, the precipitate was collected and recrystallized.
815

Compound 8 was obtained as well by adding 25 mmol MeI to the solution of oxadiazole 5 (25 mmol) in 3 ml
EtOH and allowing the mixture to stand for 12 h.
1-Isonicotinoyl-4-phenyl- and 4-(p-Chlorophenyl)-S-methylisothiosemicarbazide Methiodides (11
and 12). The solution of dithioester 7 (50 mmol) and aniline or p-chloroaniline (50 mmol) in EtOH (5 ml) was
refluxed for 4 h. On cooling down, Et2O was added and the oils precipitated. The ethereal solution was
decanted, then a small amount of MeOH was added to the residue. Crystallization was initiated by rubbing with
a glass rod. Products were purified by crystallization from MeOH.
3-(2-Hydroxyethylamino)-4-(2-hydroxyethyl)-5-(pyridin-4-yl)-1,2,4-triazole
Methiodide
(13).
Compound 7 (1.2 g, 5 mmol) and ethanolamine (2 ml, 30 mmol) were refluxed for 3 h. Upon cooling down, the
precipitate was collected.
4-(2-Hydroxyethyl)-3-methylthio-5-(pyridin-4-yl)-1,2,4-triazole Methiodide (14). Compound 6
(1.1 g, 5 mmol) was added to a solution of KOH (0.3 g, 5 mmol) in ethanol (15 ml), then methyl iodide (0.9 ml,
15 mmol) was added and the mixture was refluxed for 3 h. After cooling down, Et2O was added and the ethereal
solution was decanted from above the thick oil, which was treated with a small amount of MeOH.
Crystallization was initiated by rubbing with a glass rod. The precipitate was filtered off and recrystallized from
MeOH.
N'-(1,3-Diazacycloalkan-2-ylidene)isonicotinehydrazide Methiodides (15-18). Compound
7
(10 mmol), ethanol (10 ml) and an appropriate alkyldiamine (20 mmol) were refluxed for 0.5 h. After cooling
down, the precipitates were collected and recrystallized.
4-Amino-3-hydrazino-5-(pyridin-4-yl)-1,2,4-triazole Methiodide (19). A solution of compound 7
(1.9 g, 5 mmol) in EtOH (10 ml) was treated with hydrazine hydrate (0.25 ml, 5 mmol) and refluxed for 10 min.
On cooling down, the precipitate was filtered off and recrystallized.
N'-(1-Methyl-1,2-diaziridin-3-ylidene)isonicotinehydrazide Methiodide (20). Compound 7 (1.9 g,
5 mmol), ethanol (15 ml), and methylhydrazine (0.2 ml, 5 mmol) were refluxed for 10 min. On cooling down,
the precipitate was filtered off.
N'-(1,3-Dithiolan-2-ylidene)isonicotinehydrazide (21). To a solution of KOH (1.2 g, 20 mmol) in
EtOH (10 ml) isonicotinehydrazide (1.4 g, 10 mmol) was added, then CS2 (0.6 ml, 10 mmol) was introduced
dropwise through the reflux condenser. The mixture was clarified while stirring, then EtBr (0.86 ml, 10 mmol)
was added and the mixture refluxed for 5 min. After cooling with ice 50 ml of water was added. The precipitate
of compound 21 was filtered off and recrystallized from MeOH.
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