Download PDF
Synlett 2003(11): 1743-1745
DOI: 10.1055/s-2003-41435
LETTER
© Georg Thieme Verlag Stuttgart · New York

Sequential Cyclizations of 2-Isothiocyanatobenzonitrile with α-Amino­carboxylic Esters and Acids

Peter Langer*, Anja Bodtke
Institut für Chemie und Biochemie der Ernst-Moritz-Arndt-Universität Greifswald, Soldmannstr. 16, 17487 Greifswald, Germany
e-Mail: peter.langer@uni-greifswald.de;
Further Information

Publication History

Received 2 July 2003
Publication Date:
22 September 2003 (online)

    Permissions and Reprints All articles of this category

Abstract

The cyclization of 2-isothiocyanatobenzonitrile with α-aminocarboxylic esters and acids afforded a variety of 2-oxo-2,3,5,6-tetrahydro-5-thioxo-imidazo[1,2-c]quinazolines with very good regioselectivity.

Key words

amino acids - cyclizations - domino reactions - isothiocyanates - regioselectivity

8

Synthesis of 3-Isopropyl-2-oxo-2,3,5,6-tetrahydro-5-thioxo-imidazo[1,2-c]quinazoline(3e). Typical procedure: Isothiocyanatobenzonitrile (1.0 g, 6.4 mmol) and methyl valine ethyl ester hydrochloride (1.16 g, 6.4 mmol) were suspended in dichloromethane (40 mL). A solution of sodium carbonate (1.38 g) in water (12 mL) was added and the mixture was stirred for 10 minutes at ambient temperature and was subsequently refluxed for 20 minutes. After cooling to room temperature the organic and aqueous layer were separated and the latter was extracted twice with dichloromethane (20 mL). The combined organic layers were concentrated at reduced pressure and the residue (intermediate B) was refluxed in iso-propanol for 10 h. The product crystallized after cooling. Yield: 1.28 g (77%), colorless prisms (iso-propanol), mp 278-288 °C (decomp.). IR (KBr, cm-1): 3171 (m), 3113 (m), 3079 (m), 3027 (m), 2968 (m), 1733 (s), 1627 (s), 1557 (s), 1529 (s), 1476 (s), 1413 (m), 1348 (s), 1295 (m), 1260 (s), 1207 (s), 1149 (s), 1067 (m), 969 (m), 762 (m). UV: λmax(nm): 210.3, 247.7, 269.4, 296.3, 352.3. 1H NMR (DMSO-d 6, 300 MHz): δ 0.63 (d, J = 6.8 Hz, 3 H, CH3), 1.20 (d, J = 7.1 Hz, 3 H, CH3), 3.34-3.38 [m, 1 H, CH(CH3)2], 4.51 (d, J = 3.3 Hz, 1 H, C*H), 7.41-7.48 (m, 2 H, ArH), 7.84-8.07 (m, 2 H, ArH), 13.25 (br s, 1 H, NH). 13C NMR (DMSO-d 6, 75 MHz): δ 14.9 (CH3), 16.9 (CH3), 25.9 [CH(CH3)2], 67.9 (C-3), 110.9 (C-6a), 116.1 (Ar-CH), 125.2 (Ar-CH), 127.6 (Ar-CH), 137.1 (Ar-CH), 139.7 (C), 168.5, 168.5 (C=N, C=S), 186.5 (C=O). MS: m/z = 260 (18), 259 (M+, 100), 244 (38), 226 (23), 218 (11), 217 (70), 216 (55), 204 (36), 203 (82), 178 (36), 177 (15), 171 (11), 162 (25), 161 (59), 160 (10), 145 (19), 144 (15), 143 (19), 134 (14), 129 (15), 102 (25), 39 (10). Anal. Calcd for C13H13N3OS (259.33): C, 60.21; H, 5.05; N, 16.20. Found: C, 60.61; H, 5.48; N, 16.46. All products were obtained as racemic material. All compounds gave correct spectroscopic data and satisfactory elemental analyses and/or high resolution mass data.