Publisher Summary This chapter discusses advances in oxazole chemistry. A significant interest in the chemistry of oxazole was revived in an effort to synthesize penicillin, when this fascinating antibiotic molecule was thought to contain an oxazole ring. In this way, aspects of oxazole chemistry are studied which had received little or no attention before. The chapter explores the numerous developments made in the field of oxazole chemistry from the beginning of 1955 to the end of 1972. The emphasis has been placed on methods of synthesis and reactions of the mononuclear oxazoles; therefore, only a few references are given to condensed oxazoles (such as benzoxazoles and naphthoxazoles). The formation of oxazoles generally predominates at around 130oC when slightly more than a molar quantity of formamide is used. The oxazole synthesis is about equally successful when α-halo ketones are boiled with a mixture of ammonium formate and formic acid (large excess) in place of formamide and concentrated sulfuric acid.

Advances in Oxazole Chemistry

Efficient synthesis of multi-substituted oxazoles under solvent-free microwave irradiation

Three series of several 1,2,3-triazolo[4,5-d]pyrimidine derivatives bearing various amino substituents at the 7 position and one of three lipophilic substituents at the 3 position (benzyl, phenethyl, or 2-chlorobenzyl) were prepared starting from the corresponding 7-chloro compounds, by nucleophilic substitution by the appropriate amine. Radioligand binding assays at bovine brain adenosine A1 and A2A receptors showed that some compounds possessed a high affinity and selectivity for the A1 receptor subtype. In particular the biological results suggested the compounds bearing cycloalkylamino (cyclopentyl- and cyclohexylamino) or aralkylamino (alpha-methylbenzyl- and 1-methyl-2-phenylethylamino or amphetamino) substituents at the 7 position were the most active derivatives. The best lipophilic substituent at the 3 position was the 2-chlorobenzyl (A1 affinity Ki < 50 nM) followed by the benzyl and then the phenethyl groups. This pattern of structure-activity relationship (SAR) was similar to that previously reported for analogous 1,2,3-triazolopyridazino derivatives (Biagi et al., 1994, 1995, 1996) except for the compounds bearing substituted aromatic amines which presented a generalized and strong decrease of the A1 receptor affinity. These facts allowed us to attribute to these molecules a binding mode within the A1 adenosine receptor analogous to that of the corresponding triazolopyridazines.

Novel 3-Aralkyl-7-(amino-substituted)-1,2,3-triazolo[4,5-d]pyrimidines with High Affinity toward A1 Adenosine Receptors

Reaktionen des Trifluoracetyl-carbäthoxy-carbens II. Mitteilung

A novel and direct synthesis of 2-alkyl-5-aryl disubstituted oxazoles

Die UV-Spektren verschiedener Azole werden im Zusammenhang mit ihrer Konstitution diskutiert.

Säureamid‐Reaktionen, XX. Über die UV‐Spektren verschiedener Azole

Bei der Umsetzung der isomeren Methyl-phenyl-oxazole mit Formamid entsteht 4(5)-Methyl-5(4)-phenyl-imidazol. Aus 1-Brom-1-phenyl-butanon-(2) und dem homologen 1-Brom-1-phenyl-pentanon-(2) erhalt man mit Thioharnstoff die entsprechenden 2-Amino-4-alkyl-5-phenyl-thiazole, mit anderen Thiocarbonsaureamiden die 5-Alkyl-4-benzyl-thiazole und mit Ammoniumsalzen von Carbonsauren neben den 4-Alkyl-5-phenyl-oxazolen die 5-Alkyl-4-benzyl-oxazole.

Säureamid‐Reaktionen, XIX. Über ein anomales Verhalten von α‐Bromketonen bei der Synthese von Oxazolen und Thiazolen. — Zur Existenz tautomerer Imidazole

Die Ringaufspaltung von Oxazolen mit 2.4-Dinitrophenylhydrazin zu den Osazonen von Glyoxalderivaten wird beschrieben.

Friedrich Reich

Papers

Säureamid‐Reaktionen, XX. Über die UV‐Spektren verschiedener Azole

Säureamid‐Reaktionen, XIX. Über ein anomales Verhalten von α‐Bromketonen bei der Synthese von Oxazolen und Thiazolen. — Zur Existenz tautomerer Imidazole

Ringaufspaltung von Oxazolen mit 2.4‐Dinitrophenylhydrazin