Mendeleev Communications Electronic Version, Issue 1, 1998 (pp. 1–42) Reaction of acylisothiocyanates with 5-isopropoxy-4-methyloxazole Anton V. Dudin,* Nicolai E. Agafonov and Viktor M. Zhulin N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 117913 Moscow, Russian Federation. Fax: +7 095 135 5328 Formal [3+2]-cycloaddition of acylisothiocyanates to 5-isopropoxy-4-methyloxazole gives derivatives of 5-acylimino-3-thiazoline.In recent years, extensive studies have been carried out on the formal [3+2]-cycloaddition to oxazoles 1 accompanied by opening of the oxazole ring and formation of another heterocycle 3 (Scheme 1). A series of ‘ene’ components 2 of this reaction, such as C=C,1 C=N,2 N=N,2,3 C=O2,4 and N=O5 bonds have been studied; the addition of oxazoles to the C=S group of thioaldehydes generated in situ has also been reported.6 We found that acylisothiocyanates 4a–c reacted with 5-isopropoxy- 4-methyloxazole 5 to give hitherto unknown 5-acylimino- 2-isopropoxycarbonyl-2-methyl-3-thiazolines 6a–c, i.e.the transformation occured via formal [3+2]-cycloaddition of the C=S bond of acylisothiocyanate to the 2nd and 4th atoms of the oxazole ring (Scheme 2).Thus, we show for the first time that oxazoles react by the above mechanism not only with heteroolefins but also with heterocumulenes.† The structure of adduct 6a was confirmed by X-ray diffraction analysis‡ (Figure 1), while the structures of compounds 6b,c were established by comparing their 1H and 13C NMR and mass spectra with those of compound 6a.The authors express their gratitude to L. G. Vorontsova and M. G. Kurella who performed the X-ray diffraction analysis. References 1 (a) G. Ya. Kondrat’eva, M. A. Aitzhanova, V. S. Bogdanov and O. S. Chizhov, Izv. Akad. Nauk SSSR, Ser. Khim., 1979, 1313 (Bull. Acad. Sci. USSR, Div. Chem. Sci., 1979, 28, 1228); (b) T. Ibata, Y. Isogami, H. Nakawa, H. Tamura, H. Suga, X.Shi and H. Fujieda, Bull. Chem. Soc. Jpn., 1992, 65, 1771. 2 A. Hassner and B. Fischer, Tetrahedron, 1989, 45, 3535. 3 (a) T. Ibata, H. Suga, Y. Isogami, H. Tamura and X. Shi, Bull. Chem. Soc. Jpn., 1992, 65, 2998; (b) T. Ibata, Y. Isogami and H. Tamura, Chem. Lett., 1988, 1551. 4 H. Suga, X. Shi, H. Fujieda and T. Ibata, Tetrahedron Lett., 1991, 32, 6911. 5 H. Suga and T.Ibata, Chem. Lett., 1991, 1221. 6 E. Vedejs and S. Fields, J. Org. Chem., 1988, 53, 4663. 7 R. A. Firestone, E. E. Harris and W. Reuter, Tetrahedron, 1967, 23, 943. † 5-Benzoylimino-2-isopropoxy-2-methyl-3-thiazoline 6a was obtained by refluxing oxazole 57 (1.0 g, 7.1 mmol) and isothiocyanate 4a (1.16 g, 7.1 mmol) in toluene for 7 h under argon. The resulting mixture was chromatographed on a column with SiO2 using benzene as an eluent to give 1.50 g of compound 6a as large yellow prisms, mp 84–85.5 °C (from hexane), Rf (Silufol, Et2O–benzene, 1:1) 0.53–0.56.Found (%): C 59.00, H 5.36, N 9.29, S 10.30. Calc. for C15H16N2O3S (%): C 59.19, H 5.30, N 9.21, S 10.53. 1H NMR (300 MHz, CDCl3) d: 1.23 [m, 6H, CH(CH3)2], 2.00 (s, 3H, CH3), 5.04 [m, 1H, CH(CH3)2], 7.51 (m, 3H, Ph), 8.30 (t, 3H, Ph and N=CH). 13C NMR (75.5 MHz, CDCl3) d: 21.3 [q, CH(CH3)2], 24.7 (q, CH3), 70.7 [d, CH(CH3)2], 93.7 (s, S–C–CH3), 128.5 and 130.4 (d, Ph, o- and m-CH), 133.7 (d, Ph, p-CH), 134.4 (s, Ph, quaternary C), 163.7 (d, N=CH), 167.1 (s, N=C–S), 177.6 and 178.3 (s, N–C=O and O–C=O). MS (EI, 70 eV) m/z 304 [M]+. Adducts 6b [bp 144–145 °C (1 mmHg)] and 6c (mp 99–101.5 °C) were synthesized similarly to adduct 6a. ‡ X-ray diffraction analysis.Crystals of compound 6a in the form of tetrahedral prisms were grown from pentane, triclinic, a = 10.164(1) Å, b = 9.732(1) Å, c = 7.877(1) Å, a = 96.40(1)°, b = 93.30(1)°, g = 98.92(1)°, Z = 2, space group P , C15H16N2O3S. A complete set of 1295 independent reflections with I > 2s(I) was obtained on a RED-4 four-circle automatic diffractometer (l Cu-Ka, graphite monochromator, w–q/2q scanning, q £ 60°).The structure of compound 6a was solved by a direct method. The coordinates of non-hydrogen atoms were refined by the least-squares method in an anisotropic approximation; the hydrogen atom coordinates were refined isotropically. The final value of R was 0.07. Atomic coordinates, bond lengths and thermal parameters have been deposited at the Cambridge Crystallographic Data Centre (CCDC).For details, see Notice to Authors, Mendeleev Commun., 1998, issue 1. Any request to the CCDC should quote the full literature citation and the reference number 1135/23. N O R2 R3 R1 X Y + N X Y R1 R2 COR3 Scheme 1 1 2 3 C(19) C(18) C(20) O(3) C(17) C(21) O(4) C(9) N(6) S(1) C(7) C(8) N(5) C(10) O(2) C(11) C(12) C(13) C(14) C(15) C(16) Figure 1 The structure of compound 6a.Bond lengths (Å): S(1)–C(7) 1.763(5), S(1)–C(9) 1.859(6), O(2)–C(10) 1.227(8), O(3)–C(17) 1.345(7), O(3)–C(18) 1.461(7), O(4)–C(17) 1.226(8), N(5)–C(7) 1.283(8), N(5)–C(10) 1.421(7), N(6)–C(8) 1.292(9), N(6)–C(9) 1.401(7), C(7)–C(8) 1.429(9), C(9)–C(17) 1.492(10), C(9)–C(21) 1.513(8), C(10)–C(11) 1.519(10), C(11)–C(12) 1.341(8), C(12)–C(13) 1.391(10), C(13)–C(14) 1.363(9), C(14)–C(15) 1.417(10), C(15)–C(16) 1.435(10), C(16)–C(11) 1.383(8), C(18)–C(19) 1.527(8), C(18)–C(20) 1.512(10).Bond angles (°): C(7)– S(1)–C(9) 89.3(3), S(1)–C(7)–C(8) 107.5(5), S(1)–C(7)–N(5) 128.5(5), N(5)–C(7)–C(8) 124.0(6), C(7)–C(8)–N(6) 120.6(6), C(8)–N(6)–C(9) 112.0(6), S(1)–C(9)–N(6) 110.0(5), S(1)–C(9)–C(17) 104.0(5), S(1)–C(9)– C(21) 110.9(5), N(6)–C(9)–C(17) 109.9(5), N(6)–C(9)–C(21) 111.0(5), C(17)–C(9)–C(21) 110.8(6), C(7)–N(5)–C(10) 115.7(5), O(2)–C(10)–N(5) 125.6(7), O(2)–C(10)–C(11) 120.1(7), N(5)–C(10)–C(11) 114.3(5), C(10)– C(11)–C(12) 118.9(6), C(10)–C(11)–C(16) 119.6(7), C(12)–C(11)–C(16) 121.4(7), C(11)–C(12)–C(13) 121.3(6), C(12)–C(13)–C(14) 119.3(8), C(13)–C(14)–C(15) 121.5(8), C(14)–C(15)–C(16) 117.0(6), C(15)–C(16)– C(11) 119.2(7), C(9)–C(17)–O(4) 124.9(7), O(3)–C(17)–O(4) 120.7(6), O(3)–C(17)–C(9) 114.4(5), O(3)–C(18)–C(19) 104.6(3), O(3)–C(18)–C(20) 105.8(6), C(17)–O(3)–C(18) 119.4(5), C(19)–C(18)–C(20) 110.2(6).R C O N C S + N O Me PriO N S Me COOPri CON R 4a–c 5 6aR = Ph (69%) 6b R = Me (25%) 6c R = p-NO2C6H4 (75%) Scheme 2 1 2 3 4 5 1 Received: Moscow, 18th November 1997 Cambridge, 8th January 1998; Com. 7/08938D