A New Synthesis of Oxazole

Abstract

then decomposes into the acetylene derivative, chloride ion, and formic acid. In an analogous manner, we obtained phenylacetylene from acetophenone via chlorocinnamaldehyde and p-methoxyphenylacetylene from p-methoxyaoetophenone via (3-chloro-p-methoxycinnamaldehyde.The new reaction makes it possible to prepare many acetylene derivatives relatively easily. Received, Dcccrnber 14th. 1962 [Z 411/240 lE] [IWe have found that primary carboxamides may be. condensed with vinylene carbonate (I) [I] in polyphosphoric acid to yield 2-substituted oxazoles (2). f 1) 12)Thus, condensation of equimolar quantities of benwmide and vinylene carbonate in polyphosphoric acid (2 hrs. at 165-170°C) gave 2-phenyloxazole (b.p. 100-101 "/12 mm.) in 34% yield [2]. The corresponding reaction with m-nitrobenzamide gave 3-nitrophenyl-2'sxazole (m.p. 99-99.5 "C) in 10% yield, and that with othlorobenzamide afforded 2chlorophenyl-2'-oxazole (b.p. 100-105 OC10.6 mm) in 6% yield. The reaction failed, however, when the following amides were employed : phenoxyacetamide, phenylacetamide, pmethylbenzamide, and salicylamide. Picolinic amide gave 2-(2'-pyridyl)oxazole in about 2 yield. The formation of the oxazole m a y be accounted for by the following mechanism:The consistently moderate yields could not so far be significantly improved when the reaction conditions were changed. Because of its simplicity, however, the present new synthesis appears to deserve further investigation. Received. December 14th. 1962 [Z 413/239 IE] [I] R. W. Addor, Ph. D. thesis (No. 1485), Ohio State University (1954); M. S. Newman and R. W. Addor, I. Amer. chem. Soc. 77, 3789 (1955). We thank Dr. H. Orth of the ClBA AG., Basel, for a specimen of this compound. 12) J . University Press Princeton, N.J., 1949, p. 704. as well as W. E. Cuss, J. Amer. chem. Soc. 64,785 (1942) give a b.p. of 223-225 "C for 2-phenyl o x~l e .Lithium triphenylstanniine Li . Sn(GHS)3 Ill was prepared readily from triphenylchlorostann:tm and lithium in tetrahydrofuran. It is an efkient nucleophilic reagent and undergoes stepwise reactions with sulfur, selenium, and tellurium in tetrahydrofuran at room temperature. n (GH&SnLi + X , + n (GH3.6n-X--Li (X = S. Se, Tc)The pure monochalkogenide (2) is difficult to isolate and is formed only in the presence of a large excess of (I) (stoichiometric quantities of reactants yield a mixture of (CaHs)3s&Li products). Solutions of (2) are very reactive and are sensitive toward air and heat (condensation to Li2S and thioether if X = S). With triphenylchlorostannane, good yields of hexaphenylditin sulfide, hexaphenylditin selenide, and hexaphenylditin telluride (m.p. 148OC) are obtainable. With benzoyl chloride, the sulfur compound readily forms Lriphenyltin thiobenzoate ( c & i )~S n -S -c o -C~H~ (m.p. I08 "C). By reaction between (2) and triplienylbrornogermanium or triphenylchlorolead : (GH&SnXLi + BrOe(C&ls)3 -b LiBr + (C&ls)3snXGe(C#s)~ such compounds as (c&t~)3SnSc;e(C6Hs)3 (m. p. 135 "C), (GH5)3 (m.p. 138OC) are obtaincd; the methyl analogues of these c...

Chemistry of oxazoles

“…33•41 Oxazoles that are substituted at only the 2 position can be prepared in poor to moderate yields by the reaction of primary amides with vinylene carbonate 186 in polyphosphoric acid at 165°. 156 The mechanism shown in eq 82 was proposed for the reaction. Although this reaction does not seem to be a general method for the synthesis of 2-substituted oxazoles, it does offer the advantage of simplicity as compared with the more general synthesis reported by Cornforth and Cornforth which involves a five-step reaction sequence.2•4 on the tetralone oxime.…”

Synthesis of Polysubstituted 5-Aminooxazoles from α- Diazocarbonyl Esters and α-Isocyanoacetamides

“…Thus, various synthetic methods of oxazole derivatives have been developed. Currently, the main synthetic methods of oxazoles include cyclodehydration reactions, oxidations of oxazolines, direct derivation of the parent oxazole, and metal-catalyzed cross-coupling reactions . The most common method for the preparation of oxazoles is the cyclodehydration, but this method provides low yields of oxazoles .…”

Biphenylsulfonamide Endothelin Receptor Antagonists. 2. Discovery of 4‘-Oxazolyl Biphenylsulfonamides as a New Class of Potent, Highly Selective ETA Antagonists

“…Method 1. 28 A mixture of 4-bromobenzenecarboxamide (4 g, 20 mmol), vinylene carbonate (1.72 g, 20 mmol) and 10 g of polyphosphoric acid was heated at 170 °C for 3 h. After cooling, the mixture was partitioned between 200 mL of water and 200 mL of ethyl acetate. The aqueous layer was extracted with ethyl acetate and the combined organic liquid was washed with water, dried and concentrated.…”