Benzoxazoles 1.2- benzisoxazoles

A large body of information on the methods of synthesis, application, structure, and properties of all known five-membered nitroazoles - pyrazoles, imidazoles, triazoles, tetrazoles, oxazoles, isoxazoles, oxadiazoles, thiazoles, isothiazoles, thiadiazoles, selenazoles, selenadiazoles, and their benzo analogs - indazoles, benzimidazoles, benzoxazoles, benzisoxazoles, benzoxadiazoles, benzothiazoles, benzoisothiazoles, benzothiadiazoles, benzotriazoles, benzoselenazoles, and ben-zoselenadiazoles has been systematized, summarized, and critically discussed in this monograph. 

The benzoxazole-benzisoxazoles family of molecules is a group of molecules where five-member rings containing both nitrogen and oxygen are fused to benzene. This family of molecules has three isomers shown in Figure 6.31. 

A route to regioisomeric benzisoxazole structures featuring a key copper-catalyzed C—O bond formation has been reported. In an intramolecular cyclization similar to that shown in Scheme 24.34 for benzoxazoles, benzisoxazoles such as 64 could be synthesized from Z-conflgured o-bromoacetophenone oximes under the action of a diamine-based copper catalyst (Scheme 24.36) [128]. A range of 3-methyl-l,2-benzisoxazoles were synthesized in good yields. 

Azoles having heteroatoms in the 1,3-orlentatlon are more reactive than those in which the arrangement is 1,2. However, the magnitude of the factor varies. Thus oxazole is 68 times more reactive than Isoxazole, whereas benzoxazole quaternlzes 26 times faster than does 1,2-benzisoxazole (78AHC(22)71). 

Electron impact fragmentation studies on 1,2-benzisoxazoles and benzoxazole indicate that isomerization takes place before degradation. Shape analysis and metastable ion abundances in the mass spectra indicate that isomerization to o-cyanophenols occurred prior to degradation by loss of CO or NCH (75BSB207). 

The photolysis of 1,2-benzisoxazole in the absence of air in acetonitrile gave salicylonitrile and benzoxazole (67AHC(8)277). When air-saturated acetonitrile was employed, 2,2 -dimeriz-ation to (38) occurred, accompanied by benzoxazole. Photolysis of the 2,2 -dimer (38) and benzoxazole did not alter the ratio, thus indicating that neither one arose from the other. Selective excitation also ruled out dimer formation from benzoxazole under the reaction conditions (Scheme 9). This dimerization is similar to that observed for benzimidazole, except that in that series no 2,2 -dimerization was observed (74TL375). 

The mechanism of thermolysis and photolysis of ethers of 3-hydroxy-1,2-benzisoxazole has also been studied. Heating of the allyl ether (43) gave minor amounts of (44) and two benzoxazoles. Photolysis of (45) in methanol gave a benzisoxazole and an iminoester, via intermediate (46). Thermolysis at 600 °C gave a benzoxazole, a benzoxazolone and cyano-phenol (Scheme 16) (71DIS(D)4483). 

The sulfonate ester of o-hydroxyacetophenone oximes, when treated with pyridine, are similarly converted into a benzoxazole, but cyclize to a 1,2-benzisoxazole when treated with aqueous KOH <73JCS(P1)2220, 71T711). 

The reaction of vinylogous amides, or ketoaldehydes, with hydroxylamine produced 4,5,6,7-tetrahydro-l,2-benzisoxazole. A side product is the 2,1-benzisoxazole (Scheme 173) (67AHC(8)277). The ring system can also be prepared by the reaction of cyclohexanone enamines with nitrile oxides (Scheme 173) (78S43, 74KGS901). Base treatment produced ring fission products and photolysis resulted in isomerization to benzoxazoles (76JOC13). 

Heterocyclic compounds Heterocyclic C=N systems, such as benzoxazole and related thia-zoles, react with complex 2b to yield the ring-expanded adducts, e. g. complexes 90 and 91, by formal C-X (X = O, S) bond cleavage and coupling with the alkyne. In the case of benzisoxazole, the alkyne is not coupled but eliminated, and ring-enlargement of the ben-zisoxazole leads to the N-bridged dimer 92 [48]. 

Benzofuranes Indolines Benzothiaphenes Benzisoxazoles Benzoxazoles Benzimidazoles Benzothiazole... 

Fio. 1. Bronsted plot for azoles reacting with methylating agents in quaternization reactions. Pyridine is the reference substrate. 1, 1-methylimidazole 2, 1-methylbenzimidazole 3, thiazole 4, 1-methylpyrazole 5, 2-methylindazole 6, benzo-thiazole 7, oxazole 8, 1-methylindazole 9, benzoxazole 10, 2,1-benzisothiazole 11, isothiazole 12, 2,1-benzisoxazole 13, isoxazole and 14, 1,2-benzisoxazole. 

Sections VI,A, B, D, and E give information about indazoles, oxazole, benzoxazole, isoxazole, benzisoxazoles, isothiazole, benziso-thiazoles, and benzothiazole. In addition, Sections II and VI,F,1 refer to quaternization reactions of isoxazole and benzisothiazoles, respectively. 

Data from Siegrist (Ref. 11) for benzoxazoles and from de Sousa and Siegrist (Ref. 54) for benzisoxazoles. 

Treatment of 2- or 4-(p-formylphenyl)-2/f-l,2,3-triazoles with p-tolyl-substituted heterocycles such as benzo[6]furans,58,63 benzol-thiophenes,56,63 benzoxazoles,63,64 benzisoxazoles,54 oxazoles,63 isoxa-zoles,63 oxadiazoles,63,65 benzotriazoles,63 and y-triazolo [ 1,5-a]-pyri-dines19 has led to the formation of a number of new stilbene derivatives some of which are shown in Table XI. 

TABLE VIII Heterocyclic Styryl Derivatives of Benzoxazoles and Benzisoxazoles... 

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