[16563-14-7]  · C5H5NOS  · 4-Cyanothiolan-3-one  · (MW 127.11)

(precursor for a-substituted acrylonitriles,1 2-cyano-1,3-butadiene,2 and substituted thiophenes;3,4 building block for thienobenzodiazepines5)

Alternate Name: 4-oxothiolane-3-carbonitrile.

Physical Data: mp 71-72 °C (from diethyl ether);1,4 IR and 1H NMR spectra.1

Form Supplied in: commercially available.

Preparative Method: 1,6 can be conveniently prepared in 50% yield by cyclization of the Michael adduct of methyl thioglycolate and acrylonitrile.

Synthetic Equivalent for the a-Acrylonitrile Anion.1

Alkylation of 4-cyanothiolan-3-one with a variety of alkyl halides in the presence of Potassium Carbonate provides C-alkylated products in excellent yields. Their treatment with aqueous Sodium Hydroxide affords a-substituted acrylonitriles through tandem Dieckmann-Michael retrograde reactions (eq 1).

Synthetic Precursor for 2-Cyano-1,3-butadiene.2

This rather unstable conjugated diene can be generated and trapped in situ by dienophiles using the nicely crystalline 3-cyano-2,5-dihydrothiophene 1,1-dioxide as a suitable precursor. This precursor is derived from 4-cyanothiolan-3-one in a three-step sequence involving reduction of the carbonyl group followed by dehydration and S,S-oxidation. On heating a toluene solution of the diene in the absence of dienophiles, self-condensation takes place to afford the dimer, which has been hydrolyzed to mikanecic acid (eq 2).

3,4-Disubstituted Thiophenes.

2,5-Dihydrothiophenes, derived from enamines or enol ethers of 4-cyanothiolan-3-one, can be efficiently aromatized to the corresponding thiophene derivatives by treatment with Chloranil3,5 or Sulfuryl Chloride (eq 3).4

Building Block for Polycondensed Heterocycles.

The cyclocondensation of 4-cyanothiolan-3-one with 1,2-diaminobenzenes followed by chloranil aromatization affords biologically interesting substituted 10-amino-4H-thieno[3,4-b][1,5]benzodiazepines (1).5

Related Reagents.

Acrylonitrile; 2-(Dimethylamino)-3-butenenitrile; Lithioacetonitrile; 4-Methoxycarbonylthiolan-3-one; Methyl 3-(Dimethylamino)propionate; Methyl 3-Hydroxypropionate.

1. Baraldi, P. G.; Pollini, G. P.; Zanirato, V.; Barco, A.; Benetti, S. S 1985, 969.
2. Baraldi, P. G.; Barco, A.; Benetti, S.; Manfredini, S.; Pollini, G. P.; Simoni, D.; Zanirato, V. T 1988, 44, 6451.
3. Hromatka, O.; Binder, D.; Eichinger, K. M 1974, 105, 1164.
4. Rossy, P. A.; Hoffmann, W.; Müller, N. JOC 1980, 45, 617.
5. Chakrabarti, J. K.; Fairhurst, J.; Gutteridge, N. J. A.; Horsman, L.; Pullar; I. A.; Smith, C. W.; Steggles, D. J.; Tupper, D. E.; Wright, F. C. JMC 1980, 23, 884.
6. Georg, A. H.; Willi, M.; Heinrich, R. Dutch Patent Appl. 6 604 742, 1960 (CA 1967, 67, 21 811).

Achille Barco, Simonetta Benetti, & Gian P. Pollini

Università di Ferrara, Italy

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