Facile and High-Yielding Direct Synthesis of 2-Alkyliminothiazolines

Orazio A. Attanasi; Gianni Carvoli; Paolino Filippone; Francesca R. Perrulli; Stefania Santeusanio; Anna Maria Serri

doi:10.1055/s-2004-825610

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Synlett 2004(9): 1643-1645
DOI: 10.1055/s-2004-825610

LETTER

Facile and High-Yielding Direct Synthesis of 2-Alkyliminothiazolines

Orazio A. Attanasi^a, Gianni Carvoli^b, Paolino Filippone^a, Francesca R. Perrulli^a, Stefania Santeusanio*^a, Anna Maria Serri^b
^a Istituto di Chimica Organica della Facoltà di Scienze Matematiche, Fisiche e Naturali, Università degli Studi di Urbino ‘Carlo Bo’, Via Sasso 75, 61029 Urbino, Italy
Fax: +39(0722)303441; e-Mail: santeusanio@uniurb.it ;
^b Oxon Italia SpA, Via Sempione 195, 20016 Pero, Italy

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Publication History

Received 12 February 2004
Publication Date:
18 May 2004 (online)

Abstract
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Abstract

1,2-Diaza-1,3-butadienes readily react with O-alkylthiocarbamate derivatives via a hetero-Michael addition/cyclization reaction affording directly 2-alkyliminothiazolines in high yields under mild conditions.

Key words

1,2-diaza-1,3-butadienes - Michael additions - annulation - thiocarbamate - thiazolines

References

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The reagent was kindly supplied by Oxon Italia S.p.A.

8

Representative procedure for the preparation of 2-alkyliminothiazoline derivatives 5:
Preparation of 5a. O-Methyl ethylthiocarbamate (2a; 119 mg, 1 mmol) was dissolved in MeOH (6 mL) and 1,2-diaza-1,3-butadiene (1a; 247 mg, 1 mmol) was added portionwise to the solution with magnetic stirring at r.t. After 2 h the red color of the solution disappeared and TLC analysis indicated completion of the reaction. The desired product 5a was purified by flash chromatography on silica gel (cyclohexane-EtOAc) and crystallized from EtOAc-light petroleum ether mixture as a white powder. Analytical data of 5a: mp 156-158 °C. IR (nujol): 3302, 3258, 1706, 1645, 1599, 1563 cm^-1. ¹H NMR (400 MHz, DMSO-d ₆): δ = 1.14 (t, 3 H, J = 7.2 Hz, NCH₂CH ₃), 2.37 (s, 3 H, CH₃), 2.98-3.15 (m, 2 H, NCH ₂CH₃), 3.74 (s, 3 H, OCH₃), 6.99 (t, 1 H, J = 7.6 Hz, Ar), 7.27 (t, 2 H, J = 7.6 Hz, Ar), 7.44 (d, 2 H, J = 7.6 Hz, Ar), 8.89 (s, 1 H, NH, D₂O exchange), 9.32 (s, 1 H, NH, D₂O exchange). ¹³C NMR (100.65 MHz, DMSO-d ₆): δ = 12.57, 15.53, 47.91, 51.80, 94.58, 118.34, 122.23, 128.57, 138.80, 149.30, 152.55, 153.75, 161.44. MS: m/z (%) = 334 (6) [ M⁺], 242 (100), 200 (70), 172 (23). Anal. Calcd for C₁₅H₁₈N₄O₃S: C, 53.88; H, 5.43; N, 16.75. Found: C, 53.84; H, 5.47; N, 16.71.
Preparation of 5h. The reaction procedure, starting from 1b and 2b, is analogous to that of 5a and completion of the reaction occurs within 7 h. The product crystallizes from the reaction medium as a white powder. Analytical data of 5h: mp 168-170 °C (dec.). IR (nujol): 3393, 3345, 3291, 1719, 1674, 1649, 1631, 1612 cm^-1. ¹H NMR (400 MHz,
DMSO-d ₆): δ = 0.87 (t, J = 7.7 Hz, 3 H, CH₃), 1.33 (sext, J = 7.7 Hz, 2 H, NCH₂CH₂CH ₂CH₃), 1.48-1.58 (m, 2 H, NCH₂CH ₂CH₂CH₃), 2.31 (s, 3 H, CH₃), 3.00 (t, J = 6.4 Hz, 2 H, NCH ₂CH₂CH₂CH₃), 3.71 (s, 3 H, OCH₃), 6.36 (s, 2 H, NH₂, D₂O exchange), 8.68 (s, 1 H, NH, D₂O exchange). ¹³C NMR (100.65 MHz, DMSO-d ₆): δ = 12.52, 13.80, 19.95, 32.21, 51.65, 53.19, 94.15, 149.45, 152.60, 156.98, 161.46. MS: m/z (%) = 286 (25) [M⁺], 243 (53), 227 (70), 212 (60), 185 (37). Anal. Calcd for C₁₁H₁₈N₄O₃S: C, 46.14; H, 6.34; N, 19.57. Found: C, 46.18; H, 6.31; N, 19.53.