Preparation and spectral characterization of substituted 2-aminothiazoles

Abstract

As illustrated below, Rule I is useful for estimating the relative oximation rates of the various class members.Every alkanone (except 2-propanone, 2-butanone, and 3-pentanone) may be assigned to one of the 25 classes listed in Table I. According to Rule I the oxlmatlon rate of a given alkanone would be the same or lower than the rate of the first member of the class to which it has been assigned. The reactivity of a given class would therefore be defined if class members of increasing branching were prepared and tested until an alkanone of low reactivity was found. This was easily and completely realized for classes An, A12, B5, C4, C5, E, and F and partially realized for classes A9, A19, B2-B4, C1-C3, and D. The alkanones nones in class B, roughly parallel the corresponding members of class B2 (Rule lll-D). The remaining classes ,-Ag are generally very reactive and therefore represent the greatest area of uncertainty. ExperimentalUnless otherwise indicated in Table I the ketones were prepared by the following methods.Method A. A Grignard reagent was treated with an aldehyde and the resulting carbinol oxidized to the ketone according to the procedure of Sandborn ( 8).Method B. A Grignard reagent was converted into the cadmium dialkyl and treated with an acid chloride according to the procedure of Cason and Prout (3).Method C. An acid chloride was treated with a Grignard reagent and anhydrous ferric chloride catalyst according to the procedure of Cason and Kraus (2).The intermediates were prepared by the methods indicated in the footnotes to Table I. The malonic ester syntheses and Reformatsky reaction sequences were performed according to the procedures previously described (5).Analysis and rate determinations. The carbonyl percentages of new compounds and the 50% oximation times were determined by the methods previously described ( 5). An independent redetermination of the Í50% of 37 ketones gave an average precision of 3.1%. Literature Cited (1)

Synthesis and structure–activity relationship of aminoarylthiazole derivatives as correctors of the chloride transport defect in cystic fibrosis

“…To prepare the compounds we applied a known synthetic route with minor modifications. The desired target molecules were synthesized in a range of variable yields via the classic Hantzsch thiazole synthesis refluxing the appropriate haloketone with an equimolar amount of the respective N-substituted thiourea (a-f) in absolute ethanol [13,14] (Scheme 1).…”

The Chemistry of α-Haloketones and Their Utility in Heterocyclic Synthesis

“…The Hantzsch thiazole synthesis using the condensation of α-haloketones with thioureas [ 290 , 291 , 292 , 293 , 294 , 295 , 296 , 297 , 298 , 299 , 300 , 301 , 302 , 303 , 304 , 305 ] or thioamides [ 306 , 307 , 308 , 309 , 310 , 311 , 312 , 313 , 314 , 315 , 316 , 317 , 318 , 319 , 320 , 321 ] 129 was es-tablished a century ago [ 290 , 291 ]. It is well-known that during Hantzsch thiazole synthesis an intermediate 130a and/or a cyclic hydroxy isomer 130b is formed ( Scheme 36 ).…”

Review of the synthesis and biological activity of thiazoles

“…[14][15][16][17][18] The most efficient involves the condensation of equimolar parts of thiourea 17 and a-haloketones or a-haloaldehydes 14 to yield the corresponding 2-aminothiazoles 18 with no by-products (Scheme 5). [19] The cyclization of N-substituted thioureas 9 with halocarbonyl compounds 19 gives 2-monosubstituted aminothiazoles 20 (Scheme 6). [19] N,N-disubstituted thioureas 21 reacted with a-halocarbonyl 14 to yield 2-disubstituted aminothiazoles 22 but in lower yields [20][21][22][23] (30-70%) (Schemes 7 and 8).…”

“…[19] The cyclization of N-substituted thioureas 9 with halocarbonyl compounds 19 gives 2-monosubstituted aminothiazoles 20 (Scheme 6). [19] N,N-disubstituted thioureas 21 reacted with a-halocarbonyl 14 to yield 2-disubstituted aminothiazoles 22 but in lower yields [20][21][22][23] (30-70%) (Schemes 7 and 8).…”