5174
M. S. Chande, V. Suryanarayan / Tetrahedron Letters 43 (2002) 5173–5175
Scheme 2. Reaction conditions: (g) NaNH2/DMF, 28–30°C, 2 h. (h) NaOMe/MeOH, reflux, 2 h.
because the derivatives of thiazolidin-4-ones are known
to have biological activity.3 The underlying synthetic
strategy may obviously provide versatile routes for the
synthesis of spirocompounds by Michael additions.
Under similar experimental conditions, when Michael
addition of 1 was extended to acrylonitrile 10, the
adduct 117 was obtained in excellent yields. The IR
spectrum displayed a sharp band at 2245 cm−1 due to
CN. Claisen type condensation of 11 with diethyl mal-
onate 4 afforded the spiro derivatives 128 in quantita-
tive yields (Scheme 2).
In the presence of a base, the Michael addition of
methyl acrylate 2 with 1 could in principle lead to the
following results, (1) addition at C-5, (2) O-alkylation
or (3) additions to the imino or amido nitrogens.
All the compounds reported in this paper are novel
compounds. We have explored the scope and generality
of this strategy successfully to other heterocyclic sys-
tems which will be communicated in due course.
Surprisingly, bases like pyridine, piperidine, triethyl-
amine/tributylamine, hydroxides, alkoxides, fluoride
ions in combination with PTCs failed to catalyze the
addition and 1 was recovered in quantitative yield.
Acknowledgements
Sodamide in dry DMF was found to be ideal, the
reaction proceeding smoothly at room temperature
(Scheme 1). The addition was virtually free of side
reactions and excellent yields of Michael adducts were
obtained using stoichiometric amounts of reactants and
base. An important feature is that the reaction exhibits
striking regioselectivity yielding 3 as the only product.4
The authors are thankful to RSIC, IIT, Mumbai and
TIFR for measuring the NMR spectra of our
compounds.
References
In an alternative synthesis of 3, the Michael adduct 5,
obtained by the addition of diethyl malonate 4 to
methyl acrylate 2, was brominated to afford the a-
bromo derivative 6. The bromo derivative was found to
be highly unstable and was utilized immediately for
further reactions with thioureas 7 in the presence of
triethylamine/tributylamine to yield 3. The yields of the
products thus obtained were low in comparison to the
former route (Scheme 1).
1. Gawley, R. E. Synthesis 1976, 777.
2. Chande, M. S.; Ambhaikar, S. B. Indian J. Chem. 1996,
35B, 373.
3. Rao, R. P. J. Indian Chem. Soc. 1958, 35, 576.
1
4. Spectral data of 3c: H NMR (in ppm): 1.25–1.30 (t, 3H,
J=7.0 Hz, CH3 of carbethoxy), 2.33–2.60 (m, 7H, 2×CH2
and CH3 on aromatic ring), 3.65 (s, 3H, OCH3), 4.20–4.28
(q, 2H, J=7.0 Hz, CH2 of carbethoxy), 7.21–7.29 (m, 4H,
Ar-H), 7.55 (br, 1H, NHCO; D2O exchangeable). 13C
NMR (in ppm): 13.75 (CH3 of carbethoxy group), 20.93
(aromatic -CH3), 29.40 and 29.50 (2×CH2), 51.71 (OCH3),
62.85 (OCH2 of carbethoxy ester), 66.74 (chiral carbon),
123.31, 130.03, 135.48, 137.41 (six aromatic carbons),
167.55 (CꢁN), 172.35, 174.69, 180.86 (3×CꢁO carbons).
Mass: M+ 364, m/z 232, 207, 168, 159, 132, 103, 73, 44, 32.
Mol. formula C17H20N2O5S. Elemental analysis [calcd/
found %]: C, 56.03/56.01; H, 5.53/5.48; N, 7.69/7.56; S,
8.80/8.74.
Dieckmann condensation of 3 in the presence of metal-
lic sodium in dry benzene gave extremely poor yields of
cyclobutanone derivatives 85 as semi-solids (Scheme 1).
The carbonyl frequency, characteristic of the cyclobu-
tanone ring, was observed at 1798 cm−1 in the IR
spectrum. Compound 8 was found to be unstable and
to undergo decomposition with time.
Claisen type condensation of 3 with diethyl malonate 4
using molar equivalents of sodium methoxide in
methanol furnished the spiro derivative 96 in 86–94%
yield (Scheme 1).
1
5. Spectral data of 8c: H NMR (in ppm): 2.47 (s, 3H, CH3),
2.50–2.63 (m, 2H, CH2), 3.50 (s, 3H, OCH3 of carb-
methoxy group), 4.10–4.20 (dd, 1H, CH), 7.26–7.40 (m,
Chande, Madhukar S.
