1.2.4- Oxadiazoles, 3-acylamino

The reaction is illustrated by the conversion of the 1,2,4-oxadiazole oxime (504) into the 3-acylamino-l,2,5-oxadiazole (505). This irreversible rearrangement occurred on heating (504) in hydrochloric acid (81AHC(29)l4l). Isoxazoles also undergo this rearrangement and these are discussed in Chapter 4.16. 

Several 3-acylamino-l,2-benzisoxazoles such as (278) underwent rearrangement to 3-(o-hydroxyphenyl)-l,2,4-oxadiazoles (279) on heating with base. It has been questioned whether the same mechanism is operative in these last rearrangements (8lAHC(29)l4l, p. 150). 

The reaction of 3,4-diacyl-l,2,5-oxadiazole 2-oxides (furoxans) with activated nitriles in ionic liquids and in ethanol unexpectedly resulted in 3-acyl-4-acylamino-l,2,5-°xadiazoles (furazans) <2003MC230>. 3-Formyl-4-phenyl-l,2,5-oxadiazole Ar-oxide 105 is a good precursor for the synthesis of functional substituted furoxans (Scheme 28) <1999JME1941, 2000MOL520, 2000JFA2995>. 

The photochemistry of 3-amino- <2002JOC6253> and some 3-iV-alkylamino-5-perfluoroalkyl-l,2,4-oxadiazoles <2004JOC4108> was investigated. The latter reaction led to 5-perfluoroalkyl-l,3,4-oxadiazoles followed eventually by their conversion into 5-perfluoroalkyl-l,2,4-triazoles. 1,3,4-Oxadiazoles were also obtained by photochemical interconversion of 3-acylamino-l,2,5-oxadiazole derivatives. Mechanisms of these reactions were proposed <2004JOC4108>. Examples of these interconversions are shown in Scheme 37. 

Dipolar cycloaddition of diazomethane to aldehydes can successfully be used for the preparation of tetrahy-drooxadiazole derivatives. Photochemical interconversion of 3-acylamino-l,2,5-oxadiazole derivatives leads to 1,3,4-oxadiazoles, though the method suffers from lack of selectivity. Many reports concentrate only on the synthesis and applications of new 1,3,4-oxadiazoles substituted with a wide variety of groups without introducing much of new chemistry. 

Nitrosation of the 2-acylamino-1,3-dicarbonyl compound (126) affords an intermediate (127), which is spontaneously hydrolyzed to an A-acylamidoxime. Elimination of water produces the oxadiazole (128) (Scheme 57) <58CB1123>. Similar results have been obtained for some acyclic... 

Nitrosation of methyl 2-acylamino-3-(dimethylamino)propenoates 494 obtained from the corresponding oxazolones 493 effects the conversion of A -acylglycines to 5-substituted-l,2,4-oxadiazole-3-carboxylates 496 as shown in Scheme 7.157. ... 

Oxo-l-propenylamino)-l,2,4-oxadiazole lagern sich mit Natriumethanolat in Dimethyl-formamid in Ausbeuten von 60-80% in 4(5)-Acyl-2-acylamino-imidazole um392 ... 

Zur photo-katalysierlcn Ringoffnung von 3-Acylamino-furazanen in Gegenwart prim, und sek. Amine zu 3-Amino-l,2,4-oxadiazolen s.Lit 356 (z.B. 3-Methylamino-5-phenyl-l,2,4-oxadiazol, 45%, aus 4-Ben-zoylamino-3-methyl-furazan und Methylamin). 

Durch Umsetzung von 2-Hydroxy-l,3,4-oxadiazolen mit Amino-carbonsauren sind 5-substi-tuierte 3-Acylamino-2,4-dioxo-imidazolidine bequem zuganglich739. Aus 1,2-Diamino-benzol und 2-Hydroxy-5-phenyl bzw. 2-Mercapto-5-phenyl-1,3,4-oxadiazol crhalt man in guten Ausbcuten 2-Oxo- bzw. 2-Thiono-2,3-dihydro-benzimidazol1M> ... 

A particular case of a photochemical strategy towards functionalized benzimidazoles regards the synthesis of 2-acylamino derivatives 70, which can be obtained from irradiations in methanol of 3-(o-amino)phenyl-l,2,4-oxadiazoles 68. In this reaction, a photolytic cleavage of the ring O—N bond, followed by migration of the aryl substituent, leads to the carbodiimide intermediate 69, a precursor of the benzimidazole nucleus (Scheme 12.20) [47]. 

A series of 3-amino (or 3-N-substituted amino)-l,2,4-oxadiazoles 108 can be obtained in moderate to high yields by the photoinduced rearrangement of 3-acylamino-l,2,5-oxadiazoles (furazans) 106 irradiated in the presence of an excess of ammonia or aliphatic amines [64—66]. The reaction follows a fragmentation-cycloaddition route, with the initial formation of a nitrile and a nitrile-oxide the latter is attacked by a nitrogen nucleophilic reagent (ZH in Scheme 12.29), and the open-chain interme-... 

Buscemi, S., Frenna, V., Caronna, T. and Vivona, N. (1992) Photochemical behaviour of 1,2,5-oxadiazoles. Irradiation of some 3-acylamino-l,2,5-oxadiazoles in the presence of nucleophiles. Heterocycles, 34 (12), 2313-2322. 

Buscemi, S., Vivona, N. and Caronna, T. (1995) Photoinduced molecular rearrangements. Some investigations of the photochemical behaviour of 3-acylamino-l,2,5-oxadiazoles (furazans). Journal of Organic Chemistry, 60 (13), 4096—4101. 

Examples include the synthesis of 3-amino-l,2,4-oxadiazoles starting from 3-acylamino-5-methyl-l,2,4-oxadiazole <2002H811> and 2-aryl-l,2,3-triazoles from l,2,4-oxadiazole-3-ketone arylhydrazones <1999T12885, 2006JOC5616>. Oximes, hydrazones, formamidines, and thioureas of the furazan series also undergo base-catalyzed mononuclear rearrangements <2004RCB1121>. Nucleophilic attack at N(3) takes place in the benzofuroxan series. For example, reaction with secondary amines leads to o-nitroarylhydrazines (Scheme 55). 

Acylation of 2-amino-l,3,4-oxadiazoles produces 2-acylamino-1,3,4-oxadiazoles.1,63,124 125 A series of acylamino derivatives, mainly 2-arylsulfonylamido-l,3,4-oxadiazoles, has been prepared.48 As has been mentioned, the l,3,4-oxadiazolin-5-ones exist in the oxo form at least in the solid state. Acetylation proceeds with substitution of the ring nitrogen [Eq. (12)]. The possibility of O-acetylation... 

Amino-l,2,4-oxadiazolcs (11) arc excellent sources of amidines. When they are treated with 1,3-dicarbonyl derivatives they are converted into enaminones (12), which cyclize to imidtizolcs in the presence of bases (Scheme 2.2.5). This reaction utilizes the well-known general attack of a nucleophilic group in the side chain at N-2 of the oxadiazole ring. Yields of 2-acylamino-4-acylimidazoles usually lie between 60 and 80% [21]. The free amino derivatives are readily isolated after acid hydrolysis. 

---