Mendeleev
Communications
Mendeleev Commun., 2011, 21, 108–109
Ketenimine N-functionalization of thiazolidine-2,4-diones
with acetylenes and isocyanides
Issa Yavari,* Tayebeh Sanaeishoar, Leila Azad and Maryam Ghazvini
Department of Chemistry, Science and Research Branch, Islamic Azad University, Ponak, Tehran, Iran.
Fax: +98 21 8288 3455; e-mail: yavarisa@modares.ac.ir
DOI: 10.1016/j.mencom.2011.03.018
The zwitterionic 1:1 intermediates formed in the reaction between alkyl isocyanides and dialkyl acetylenedicarboxylates are trapped
by 2,4-thiazolidine-2,4-diones to afford N-functionalized 2,4-dioxothiazolidines containing a ketenimine moiety.
Reaction between isocyanides, electron-deficient acetylenes and
nucleophiles leading to ketenimines, as outlined in Scheme 1,
was first documented by Oakes et al.1,2 and applied to dialkyl
acetylenedicarboxylates (X = CO2R) and 1,1,1,4,4,4-hexafluoro-
but-2-yne (X = CF3) as acetylenic component and methanol as
NuH. Such interesting and promising transformation was nearly
forgotten untilYavari et al.3 extended its application to dibenzoyl-
methane as NuH. Later on, more works on such a reaction were
published differing mostly in the nature of NuH used.4–15
2,4-dione 3a or 5-arylidene-2,4-thiazolidinediones 3b–g, as a
proton source/nucleophile, affords the corresponding highly func-
tionalized ketenimines 4 in fairly good yields.†
The highly functionalized ketenimines 4 are quite stable; they
were recovered unchanged after refluxing in toluene for 3 h. The
structures of compounds 4 were deduced from their IR, 1H and
1
13C NMR spectral data. The H NMR spectrum of 4a showed
signals for methoxy (d 3.70 and 3.77 ppm), methylene (d 3.99 ppm)
and methine (d 5.99 ppm) protons, together with multiplet for the
cyclohexyl (d 1.20–1.81 and 4.14 ppm) protons. The 13C NMR
spectrum of 4a exhibited 16 resonances in agreement with the
proposed structure. 1H and 13C NMR spectra of 4b–k were similar
to those of 4a except for the side chains, which exhibited charac-
teristic resonances in the appropriate regions of the spectra. The
sp2-hybridized carbon atom of the ketenimine moiety in com-
pounds 4 appears at d 60.8–65.6 ppm, as a result of strong electron
delocalization. IR spectra of compounds 4 show strong absorp-
tion bands at 2074–2082 cm−1 for the C=C=N moieties.
X
X
N
H
+
+
NuH
R
R
N C
C
Nu
X
X
X = CO2R, CF3
Scheme 1
Here, we report on the application of such chemistry on highly
functionalized thiazolidine-2,4-diones as N-nucleophilic counter-
part (Scheme 2, Table 1). Thus, the reaction of isocyanides 1
with acetylenedicarboxylates 2 in the presence of thiazolidine-
A plausible mechanism for formation of compounds 4 is re-
presented in Scheme 3 (cf. refs.1–3). It is conceivable that the
reaction involves the initial formation of the 1:1 zwitterionic
intermediate 5 between isocyanide and the acetylenic ester. The
protonation of 5 by the NH-acidic compound and the subsequent
attack of the resulting nucleophile on the positively charged species
6 afforded ketenimine 4.
In conclusion, the three-component reaction of alkyl iso-
cyanides with dialkyl acetylenedicarboxylates in the presence of
thiazolidinediones provides a simple one-pot synthesis of stable
functionalized ketenimines of potential value. This procedure
O
O
CO2Alk
+
CO2Alk
Et2O
Z
S
Z
S
+
N
R
N
C
NH
room
temperature,
12 h
C
NR
1a,b
CO2Alk
O
O
CO2Alk
4a–k
2a,b
3a–g
Scheme 2
† Chemicals were purchased from Merck and used without further purifica-
tion. Compounds 3b–g were prepared from 3a by the reported method.16
Synthesis of compounds 4 (general procedure). Alkyl isocyanide 1
(1 mmol) in 2 ml of Et2O was added dropwise to a stirred solution of
thiazolidinedione 3 (1 mmol) and acetylenic ester 2 (1 mmol) in 5 ml
of Et2O at room temperature. After completion of the reaction [12 h;
TLC (AcOEt/hexane, 2:1)], the solvent was removed under reduced pres-
sure and the residue was purified by column chromatography [silica gel
(230–240 mesh; Merck), hexane/AcOEt, 4:1].
For 4a: pale yellow oil, yield 0.33 g (91%). IR (nmax/cm−1): 2081 (C=C=N),
1747 and 1700 (C=O). 1H NMR, d: 1.20–1.81 (m, 10H, 5CH2), 3.70 (s,
3H, MeO), 3.77 (s, 3H, MeO), 3.99 (s, 2H, CH2S), 4.14 (m, 1H, CHN),
5.99 (s, 1H, CH). 13C NMR, d: 24.2 (CH2), 25.7 (CH2), 33.4 (CH2), 33.5
(CH2), 34.1 (CH2), 35.9 (CH2S), 52.2 (CHN), 53.2 (MeO), 53.7 (MeO),
57.7 (CH), 60.8 (C=C=N), 161.1, 167.4, 170.1, 170.5 and 171.3 (C=C=N
and 4C=O). Found (%): C, 52.4; H, 5.3; N, 7.7. Calc. for C16H20N2O6S (%):
C, 52.16; H, 5.47; N, 7.60.
Table 1 Reaction of isocyanides, acetylenic esters and 2,4-thiazolidine-
diones.
Acetylenic Thiazolidine-
ester, Alk dione, Z
Yield
(%)
Isocyanide, R
Product
1a, cyclohexyl
1a, cyclohexyl
1b, Me3CCH2CMe2 2a, Me
1b, Me3CCH2CMe2 2b, Et
1a, cyclohexyl
1a, cyclohexyl
1a, cyclohexyl
1a, cyclohexyl
1a, cyclohexyl
1a, cyclohexyl
2a, Me
2b, Et
3a, CH2
3a, CH2
3a, CH2
3a, CH2
4a
4b
4c
4d
4e
91
88
90
88
88
85
87
75
80
85
77
2a, Me
2a, Me
2a, Me
2a, Me
2a, Me
2a, Me
3b, PhCH=C
3c, 4-MeC6H4CH=C 4f
3d, 3-MeC6H4CH=C 4g
3e, 4-O2NC6H4CH=C 4h
3f, 4-FC6H4CH=C
3g, 2-thienyl-CH=C 4j
3c, 4-MeC6H4CH=C 4k
4i
For characteristics of compounds 4b–k, see Online Supplementary
Materials.
1b, Me3CCH2CMe2 2a, Me
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Yavari, Issa
