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Synlett 2010(12): 1859-1861  
DOI: 10.1055/s-0030-1258108
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Direct Access to Variously Substituted 2-Imino-4-thiazolines

Orazio A. Attanasi, Gianfranco Favi, Paolino Filippone, Francesca R. Perrulli, Stefania Santeusanio*
Istituto di Chimica Organica della Facoltà di Scienze e Tecnologie, Università degli Studi di Urbino ‘Carlo Bo’, Via I Maggetti 24, 61029 Urbino, Italy
e-Mail: stefania.santeusanio@uniurb.it;
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Publication History

Received 26 March 2010
Publication Date:
30 June 2010 (online)

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Abstract

1,2-Diaza-1,3-dienes readily react as Michael acceptors with thiocyanic acid generated in situ from potassium thiocyanate. The acidic medium of the reaction promotes the intramolecular ring closure of the α-thiocyanato hydrazones allowing access to novel 2-imino-4-thiazolines functionalized at positions 3, 4, and 5 in a one-pot, high-yielding process.

Key words

1,2-diaza-1,3-dienes - thiocyanation - Michael addition - ring closure - 2-imino-4-thiazoline - heterocycles

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Typical One-Pot Procedure for the Preparation of 2-Imino-4-thiazoline Derivatives 4a-k
The requisite 1,2-diaza-1,3-butadiene 1a-k (1 mmol), prepared and used as an E,E/E,Z isomer mixture,¹c was added to a solution of KSCN (106.7 mg, 1.1 mmol) in glacial AcOH (2 mL) under magnetic stirring. The consumption of 1a-k was rapid and TLC analysis indicated the presence one major product. The reaction mixture was allowed to stand at r.t. overnight to allow complete conversion of the Michael adduct into the corresponding 2-imino-4-thiazoline derivative. AcOH was removed in vacuo, the residue was dissolved in H2O, and the solution neutralized with sat. Na2CO3. Compounds 4a-c,e,g-i were obtained by extraction of the aqueous phase with Et2O. The dried organic layers were filtered and evaporated, and the crude compounds were isolated as powders or foams and purified by recrystallization or by flash chromatography on silica. Compounds 4d,f,j,k, precipitated from the aqueous medium after addition of sat. Na2CO3 and were isolated by filtration and recrystallized from an appropriate solvent mixture

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Data for tert -Butyl-2-[3-(dimethylamino)-1-methyl-3-oxo-2-thiocyanatopropylidene]hydrazinecarboxylate (3j)
White powder from EtOAc-cyclohexane; mp 139-140 ˚C (dec.). IR (KBr): 3467, 3331, 2153, 1746, 1650, 1503 cm-¹. ¹H NMR (400 MHz, DMSO-d 6): δ = 1.45 (s, 9 H, Ot-Bu), 1.86 (s, 3 H, CH3), 2.86 and 2.97 [2 s, 6 H, N(CH3)2], 5.79 (s, 1 H, CH), 10.00 (s, 1 H, NH). ¹³C NMR (100 MHz DMSO-d 6): δ = 12.3 (q), 28.0 (q), 35.9 (q), 37.1 (q), 61.0 (d), 79.8 (s), 112.4 (s), 144.9 (s), 152.6 (s), 164.7 (s). ESI-MS: m/z calcd for C12H20N4O3S: 300.4; found: 301 [M + 1].

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Data for tert -Butyl {5-[(Dimethylamino)carbonyl]-2-imino-4-methyl-1,3-thiazol-3 (2 H )-yl}carbamate (4j)
White powder from EtOAc-cyclohexane; mp 159-160 ˚C (dec.). IR (KBr): 3318, 3255, 3203, 1736, 1631, 1606 cm-¹. ¹H NMR (400 MHz, DMSO-d 6): δ = 1.38 and 1.43 (2 s, 9 H, Ot-Bu), 1.89 (s, 3 H, CH3), 2.93 [s, 6 H, N(CH3)2], 8.18 (br s, 1 H, NH), 9.64 (br s, 1 H, NH). ¹³C NMR (100 MHz DMSO-d 6): δ = 12.7 (q), 27.6 and 27.8 (2 q), 36.6 (q), 40.1 (q), 80.5 (s), 98.5 (s), 136.9 (s), 154.6 (s), 157.9 (s), 162.8 (s). ESI-MS: m/z calcd for C12H20N4O3S: 300.4; found: 301 [M + 1].