Synthesis and reactions of indane-1,3-dione-2-thiocarboxanilides with hydrazonoyl halides and active chloromethylene compounds

Article abstract of DOI:10.1002/hc.10132

A novel synthesis of thiadiazoline derivatives 12 and 14 via treatment of indane-1,3-dione-2-thiocarboxanilides (5) with hydrazonoyl halides 1 and 2 is reported. Also, active chloromethylene compounds 15 react with 5 to give thiazole derivatives 19.

Full text of DOI:10.1002/hc.10132

Heteroatom Chemistry
Volume 13, Number 7, 2002
Synthesis and Reactions of
Indane-1,3-dione-2-thiocarboxanilides
with Hydrazonoyl Halides and Active
Chloromethylene Compounds
Nehal M. Elwan, Huwaida M. Hassaneen, and Hamdi M. Hassaneen
Department of Chemistry, Faculty of Science, Cairo University, Giza 12613, Egypt
Received 29 November 2000; revised 25 April 2001
conditions. The objective of this work was to shed
ABSTRACT: A novel synthesis of thiadiazoline
more light on the actual pathway of the reactions in
derivatives 12 and 14 via treatment of indane-
question and the factors influencing it. In addition,
1,3-dione-2-thiocarboxanilides (5) with hydrazonoyl
this investigation led to a one-step synthesis of 2,3-
halides 1 and 2 is reported. Also, active chloromethy-
dihydrothiadiazole derivatives.
lene compounds 15 react with 5 to give thiazole deriva-
ꢀ
C
tives 19. 2002 Wiley Periodicals, Inc. Heteroatom Chem
13:585–591, 2002; Published online in Wiley InterScience
(www.interscience.wiley.com). DOI 10.1002/hc.10132
RESULTS AND DISCUSSION
The preparation of the starting thioanilides (5) was
accomplished by addition of each aryl isothiocyanate
(3) to a solution of indane-1,3-dione (4) in dimethyl-
formamide in the presence of potassium hydrox-
ide at room temperature, followed by acidification
with dilute hydrochloric acid. The structures of
thioanilides 5a–d were established on the basis of
INTRODUCTION
The high dipolarophilic activity of the C S double
bond towards 1,3-dipoles is known [1]. Recently,
it was indicated that the reactions of C-acyl-N-
arylnitrilimines with active methine thioanilides
yield the corresponding thiazoline derivatives [2,3].
More recently, Hassaneen et al. reported that hy-
drazonoyl halides 1 and 2 reacted with thioanilides
to give the corresponding thiadiazoles via elimina-
tion of the arylamine moiety [4–6]. Inspired by these
different results, we thought it necessary to explore
further the reactions of active methine thioanilides
with different nitrilimines. For this purpose, indane-
1,3-dione-2-thiocarboxanilides (5) were prepared
(Scheme 1) and their reactions with different ni-
trilimines were investigated under different reaction
1
elemental analysis and spectral data (IR, H NMR,
MS). For example, the mass spectrum of 5a showed
an intense molecular ion peak at m+/z 281. The IR
spectrum revealed two absorption bands at 1697 and
1664 cm−1 assignable to indane-1,3-dione carbonyl
groups and a band at 3217 cm−1 assignable to an
1
NH group. Its H NMR spectrum showed two sin-
glet signals at δ 11.7 and 14.1 assignable to NH and
SH protons, respectively, as well as a multiplet signal
due to aromatic protons at δ 7.0–7.4.
Moreover, the structures of thioanilides 5 were
confirmed by their reactions with hydrazonoyl
halides 1 and 2 and with active chloromethylene
compounds 15a–d as described later. The reac-
tion of N-phenylbenzohydrazonoyl chloride (1a)
with indane-1,3-dione-2-thiocarboxanilide (5a) in
Correspondence to: Hamdi M. Hassaneen.
2002 Wiley Periodicals, Inc.
c
ꢀ
585

586 Elwan, Hassaneen, and Hassaneen
SCHEME 1
SCHEME 2

Synthesis of Thiadiazoline Derivatives 12 and 14 587
chloroform in the presence of triethylamine afforded
a product which analyzed correctly for C23H14N2O2S.
Two possible structures can be suggested for this
product—9a and 12a (Scheme 2).
cyclization to give 11 which in turn eliminates
arylamine to afford 12. Alternatively, cycloaddi-
tion of nitrilimine (6), generated in situ from 1
by the action of triethylamine, to the C S dou-
ble bond of 5a would give 11 directly, which
upon elimination of arylamine would lead to 12a.
Similarly, hydrazonoyl halides 1b and c were re-
acted with 2-thiocarboxanilide (5) to give the
corresponding 1,3,4-thiadiazoline derivatives 12b
and c.
Next, reaction of ꢁ-ketohydrazonoyl halides 2
with thioanilide 5 was then studied to investigate
the effect of the presence of a carbonyl group on the
course of the reaction. Compound 5 reacted with
ꢁ-ketohydrazonoyl halides (2) in refluxing chlo-
roform in the presence of triethylamine to give
the corresponding thiadiazoline derivatives 14
(Scheme 3). Compound 13 was discarded from
consideration on the basis of elemental analysis and
Structure 9a was rejected for the following
reasons: (i) the reaction product was recovered
unchanged after treatment with mercuric oxide in
boiling acetic acid; (ii) the C S double bond is
known to be more reactive as a 1,3-dipolarophile
than is the C C double bond; [7] and (iii) reaction
of nitrilimines with ꢀ-ketothioanilide in the pres-
ence of triethylamine has been reported to yield
2-alkylidene-1,3,4-thiadiazoline derivatives with the
elimination of the arylamine moiety [8].
To account for the formation of 12a, two alter-
native pathways (route A and route B outlined in
Scheme 2) are proposed. In route A it was suggested
that the reaction starts with the formation of thiohy-
drazonate ester (10) followed by intramolecular
SCHEME 3

588 Elwan, Hassaneen, and Hassaneen
spectral data. For example, the IR spectra of the
product 13 would reveal only two carbonyl absorp-
tion bands of indane-1,3-dione and the absence of
the carbonyl absorption band of the aryl group; such
a band is present in the spectrum of each product
14.
at m+/z 378. The structure of 14a was further con-
firmed by an alternative synthesis. Thus, reaction of
3a with 5b or 5c or 5d gave a product identical in
all respects (mp., mmp., IR, 1H NMR, MS) with 14a
(Scheme 3).
In the course of our study of the reaction of
indane-1,3-dione-2-thiocarbox-anilides (5) with
hydrazonoyl halides 1 and 2, it was found that the
reactions proceed via elimination of an arylamine
to give 12 and 14, respectively. This finding influ-
enced us to investigate the reaction of 5 with active
chloromethylene compounds 15a–d to see if such
reactions will lead to thiazolines and/or 1,3-
oxathioles. Previous literature reports indicated that
reactions of ꢁ-halo derivatives of simple ketones and
The structures of 12 and 14 were confirmed on
the basis of elemental analyses and spectral data
(IR,1H NMR, MS). For example, the IR spectrum of
compound 14a showed absorption bands at 1742,
1697, and 1645cm−1 corresponding to the (three CO)
1
groups. Its H NMR spectrum revealed the signals
of a triplet at δ 1.5 (3H), a quartet at δ 4.5 (2H),
and a multiplet at δ 7.3–7.6 (9H). The mass spec-
trum of 14a showed an intense molecular ion peak
SCHEME 4

Synthesis of Thiadiazoline Derivatives 12 and 14 589
esters with potassium salts of acyclic thioamides
[2,3,9] afforded the thiazolines and/or 1,3-oxathioles
[10].
not with 1,3-oxathiole-2-ylidene derivative 17. To
account for the formation of 19, we suggest the
mechanism outlined in Scheme 4. The reaction is
initiated by a nucleophilic addition of the sulfur
atom of 5 to the carbonyl group of 15 to give
the ketene N,S-acetal (16). Then, 16 undergoes
cyclization to yield the intermediate 18 which then
eliminates a water molecule to afford 19 (Scheme 4).
The elemental analyses and spectral data (IR, 1H
Treatment of 5a with 15a–d in dimethylfor-
mamide afforded a single product, in each case, as
1
evidenced by TLC and H NMR spectral analyses
of the crude products. Both elemental analyses
and spectral data were found compatible with
2,3-dihydro-3-phenylthiazole derivatives 19 but
TABLE 1 Characterization Data of the Newly Synthesized Compounds
% Analysis
Calculated/Found
Comp. No.
5aa
m. p. (◦C)
135
Yield (%)
Mol. Formula [Mol. Wt.]
C16H11NO2S[281]
C
H
N
S
78
70
69
75
80
68.3
68.2
69.2
70.1
60.9
61.0
53.3
53.2
72.2
72.3
73.5
73.4
64.6
64.7
63.4
63.4
65.5
65.7
70.2
70.5
63.4
63.3
59.6
60.0
58.0
58.1
58.2
58.3
64.3
64.4
64.8
64.7
70.7
70.6
64.2
64.1
71.2
71.3
76.7
76.6
67.5
67.4
75.6
75.8
3.9
3.8
4.4
4.5
3.2
3.3
2.8
3.1
3.7
3.9
3.9
4.1
3.1
3.1
3.7
3.6
3.5
3.2
3.4
3.2
2.9
2.8
2.9
2.9
2.8
2.9
3.2
3.3
4.1
4.0
2.9
2.8
3.8
3.9
3.3
3.2
4.1
4.4
3.9
3.8
4.3
4.2
4.0
3.8
5.0
4.9
4.7
4.8
4.4
4.5
3.9
3.8
7.3
7.1
6.9
6.8
9.8
9.7
7.4
7.2
8.0
7.9
6.8
6.5
6.7
6.4
7.3
7.6
10.7
10.6
6.8
6.5
7.1
7.4
6.3
6.1
6.6
6.6
6.5
6.2
6.4
6.4
2.9
2.8
3.6
3.7
3.7
3.6
11.4
11.4
10.8
10.8
10.1
10.1
8.9
8.8
8.4
8.2
7.8
7.9
7.5
7.3
8.5
8.3
9.2
9.5
7.8
7.6
15.4
15.1
8.4
8.7
8.2
8.1
7.8
7.5
8.2
8.5
7.2
7.2
7.6
7.4
14.9
14.6
7.3
7.4
6.6
6.5
8.2
8.3
8.4
8.3
5ba
151
C17H13NO2S[295]
5ca
182
C16H10NclO2S[315.5]
C16H10NbrO2S[360]
C23H14N2O2S[382]
5da
186
12aa
310
12bb
12cb
14aa
14bb
14ca
14da
14ea
14fa
250
300
262
300
234
210
267
255
236
243
308
305
320
280
227
299
270
78
76
80
75
74
76
75
75
80
80
74
74
76
70
76
74
65
C25H16N2O2S[408]
C23H13N3O4S[427]
C20H14N2O4S[378]
C19H12N2O3S[348]
C24H14N2O3S[410]
C22H12N2O3S2[416]
C19H11N2ClO3S[382.5]
C19H11N3O5S[393]
C20H13N2ClO4S[412.5]
C21H16N2O4S[392]
C24H13N2ClO3S[444.5]
C25H16N2O3S[424]
C23H14N2O3S2[430]
C26H18N2O3S[438]
C31H19NO3S[485]
14ga
14ha
14ib
14ja
14kb
19ab
19bb
19ca
19db
C22H17NO4S[391]
C24H15NO2S[381]
aAcOH is the solvent used for the synthesis of these compounds.
bDMF is the solvent used for the synthesis of these compounds.

590 Elwan, Hassaneen, and Hassaneen
NMR, MS) of all compounds are in agreement with
the suggested structure 19. For example, the IR spec-
trum of compound 19c revealed three absorption
bands at 1718, 1690, and 1636 cm−1 assignable to
ester carbonyl and indane-1,3-dione carbonyl
Hydrazonoyl halides 1,2 [11–18] and 15b [19] were
prepared as previously reported.
Indane-1,3-dione-2-thiocarboxanilides 5a–d
1
groups, respectively. Its H NMR spectrum showed
General Procedure. To a stirred suspension
of potassium hydroxide (0.28 g, 5 mmoles) in
dimethylformamide (20 ml), indane-1,3-dione (4)
(0.73 g, 5 mmoles) was added. To the resulting
solution, the appropriate aryl isothiocyanate (3)
(5 mmoles) was added and the reaction mixture
typical ethyl pattern signals, a triplet at δ1.4 and a
quartet at δ 4.4. Also, it showed a singlet signal at
δ 2.3 (3H) in addition to a multiplet signal at δ
7.1–7.7 (9H) assignable to methyl and aromatic
protons, respectively. An intense molecular ion peak
at m+/z 391 characterized the mass spectrum of
19c.
was stirred for 24
h at room temperature.
The solution was acidified with dilute hydrochlo-
ric acid (30 ml, 10%). The solid that formed
was collected, washed with water, and crystallized
from a suitable solvent to give the corresponding
thioanilides 5a–d (Tables 1 and 2).
EXPERIMENTAL
Melting points were determined on a Gallenkamp
electrothermal apparatus and are uncorrected.
Infrared spectra (KBr) were recorded on a Pye
Unican SP-300 IR spectrophotometer and Testscan
2,3-Dihydro-1,3,4-thiadiazoles 12a–c
1
Shimadzu FT-IR 8000 series. The H NMR spectra
in CDCl3 were recorded on Varian Gemini 200 and
Varian EM 390 spectrometers with TMS as the in-
ternal standard. Mass spectra were recorded on a
GCMS-QP 1000-EX Shimadzu, Japan instrument.
Elemental analyses were carried out at the Micro-
analytical Center, University of Cairo, Giza, Egypt.
Method A. Equimolecular quantities of thio-
anilides 5, hydrazonoyl halides 1 and triethylamine
(5 mmoles each) were dissolved in chloroform
(30 ml). The reaction mixture was refluxed for 6 h.
The excess solvent was evaporated under reduced
pressure, and the residue was treated with methanol
TABLE 2 Spectral Data of the Newly Synthesized Compounds
Comp. No.
ν
(cm−1)
δH (ppm)
m/z
281
295
max
5a
5b
3217 (NH), 1697 (CO), 1664 (CO)
3239 (NH), 1680 (CO), 1660 (CO)
7.0–7.4 (m, 9H, Ar-H), 11.7 (s, 1H, NH),
14.1 (s, 1H, SH)
2.4 (s, 3H, CH3), 7.2–7.6 (m, 8H, Ar-H),
11.7 (s, 1H, NH), 14.1 (s, 1H, SH)
5c
3242 (NH), 1705 (CO), 1678 (CO)
3243(NH), 1705 (CO), 1678 (CO)
1688 (CO), 1641 (CO)
1695 (CO), 1649 (CO)
1687(CO), 1647 (CO)
1742 (CO), 1697 (CO), 1645 (CO)
1697 (CO), 1645 (CO)
1697 (CO), 1647 (CO), 1628 (CO)
1699 (CO), 1645 (CO), 1624 (CO)
1701 (CO), 1644 (CO)
1688 (CO), 1641 (CO)
1739 (CO), 1700 (CO), 1645 (CO)
1739 (CO), 1696 (CO), 1645 (CO)
7.0–7.6 (m, 8H, Ar-H), 11.8 (s, 1H, NH), 14.2 (s, 1H, SH)
7.1–7.8 (m, 8H, Ar-H), 11.6 (s, 1H, NH), 14.0 (s, 1H, SH)
315
360
382
408
427
378
348
410
416
382
393
412
392
5d
12a
12b
12c
14a
14b
14c
14d
14e
14f
7.2–7.7 (m, Ar-H)
7.3–8.5 (m, Ar-H)
1.5 (t, 3H, CH3), 4.5 (q, 2H, CH2), 7.3–7.6 (m, 9H, Ar-H)
2.6 (s, 3H, CH3), 7.7–7.9 (m, 9H, Ar-H)
7.3–8.4 (m, Ar-H)
7.3–8.5 (m, Ar-H)
2.7 (s, 3H, CH3), 7.2–7.7 (m, 8H, Ar-H)
14g
14h
1.4 (t, 3H, CH3), 4.5 (q, 2H, CH2), 7.3–7.8 (m, 8H, Ar-H)
1.4 (t, 3H, CH3), 2.5 (s, 3H, CH3), 4.5 (q, 2H, CH2),
7.0–7.8 (m, 8H, Ar-H)
14i
1697 (CO), 1631 (CO)
1696 (CO), 1647 (CO)
1698 (CO), 1646 (CO)
3308 (NH), 1684(CO), 1670, 1628 (CO)
1712 (CO), 1672(CO), 1663 (CO)
1718 (CO), 1690(CO), 1636 (CO)
444
424
430
438
485
391
14j
2.5 (s, 3H, CH3), 7.1–8.4 (m, 13H, Ar-H)
2.6 (s, 3H, CH3), 7.2–8.4 (m, 11H, Ar-H)
2.1 (s, 3H, CH3), 7.1–7.7 (m, 14H, Ar-H), 8.3 (s, 1H)
7.2–7.8 (m, Ar-H)
1.4 (t, 3H, CH3), 2.3 (s, 3H, CH3), 4.4 (q, 2H, CH2),
7.1–7.7 (m, 9H, Ar-H)
14k
19a
19b
19c
19d
1677 (CO), 1630 (CO)
381

Synthesis of Thiadiazoline Derivatives 12 and 14 591
(10 ml). The solid that formed was collected, washed
with water, and finally crystallized from a suitable
solvent to give the corresponding 1,3,4-thiadiazoles
(12a–c).
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