Preparation of 2-Styrylthiazoles from 2-Methylthiazoles: An improved procedure and mechanistic aspects

Tetrahedron Letters

Volumn 37, Issue 48, 1996, Pages 8659-8662

  Van Arnum, Susan D ^a   Ramig, Keith ^a,b   Stepsus, Nancy A ^a,c   Dong, Yong ^a,d   Outten, Robert A ^a  

^a HOFFMANN LA ROCHE INC   (United States)

^b BRISTOL MYERS SQUIBB   (United States)

^c Synthesis Development   (United States)

^d BOEHRINGER INGELHEIM PHARMACEUTICALS INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

THIAZOLE DERIVATIVE;

ARTICLE; CHEMICAL REACTION; SYNTHESIS;

EID: 0030602221     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(96)02003-5     Document Type: Article

References (15)

1. 2.a Williams, D. R.; Brooks, D.A.; Moore J.L.; Stewart, A.O. Tetrahedron Lett., 1996, 37, 983 and references cited therein.
2. b. Savarino, P.; Carpignano, R.; Viscardi, G.; Barni, E.; Di Modica, G. J. Heterocycl. Chem. 1988, 25, 1675.
3. c. Cantello, B. C. C.; Cawthorne, M. A.; Haigh, D.; Hindley, R. M.; Smith, S. A.; Thurlby, P. Bioorg. Med. Chem. Lett. 1994, 4, 1181.
4. 3. US 5,001,140, Field, G.; Vermeulen, J.; Zally, W. (to Hoffmann-La Roche) 1991.
5. 4. EP 219436-A, Hayasi, Y.; Oguri, T.; Shinoda, M.; Tsutsui, M.; Takahashi, K.; Miida, H. (to Mitsubishi Chem. Ind. Ltd.) 1986.
6. 5. Erlenmeyer, H.; Weber, O.; Schmidt, P.; Kung, G. Helv. Chim Acta. 1948, 31, 1142.
7. b. JP 52083742, 1977. Chem. Abstr: 88: 6863 (1978)
8. 6. Abbotto, A.; Bradamante, S.; Pagani, G. Gazz. Chim. Ital., 1994, 124, 301.
9. 7. For a review see Gschwend, H.W.; Rodriguez, H.R. Org. React. 1979, 26, 1.
10. a of 2,4-dimethylthiazole is 3.91. For a discussion see, Metzger, J.V.; Vincent, E.J. "Properties and Reactions of Thiazoles" in Chemistry of Heterocyclic Compounds, Part One (J.V. Metzger, Ed.) John Wiley & Sons: New York, 1979.
11. 9. For example 2a, the hydrobromide salt was used and neutralized in situ. It was prepared by the reaction of bromomethyl cyclobutyl ketone and thioacetamide.
12. 10. Except in the case of anisaldehyde, the excess aldehyde was removed by conversion to its bisulfite adduct.
13. 11 2a was isolated as its hydrochloride salt.
14. 1H NMR. After 17 hours, the reaction was complete and mixture was cooled. Ethyl acetate was added and the reaction was extracted with water and saturated sodium bicarbonate. Excess aldehyde was removed by extraction with saturated sodium bisulfite solution. Chromatographic purification (20% ethyl acetate/ hexane) yielded 3.45 g (80%) of 2b. An analytical sample was prepared by recrystallization with ethanol and 2b was obtained as an orange yellow solid (MP 91-93°C).
15. 13. All new compounds gave satisfactory spectral data and either correct microanalysis or high resolution mass spectral data.