Isoxazoles and their Benzo Derivatives

Structural investigation of 3,5‐disubstituted isoxazoles by 1H‐nuclear magnetic resonance

“…In fact this reaction proceeds through an attack of hydrox- ylamine on the electrophilic center, and this is important for the subsequent ring closure to isoxazole. Since this reaction depends on the nature of R and R', all the variables which affect enolization (such as acidity or alkalinity of the medium) may influence the ratio in which the two isomers are formed [12]. According to Barnes et al [19], in the highly enolized diketones, which possess alternative H-bonded (tautomeric structures), the structure of the principal reaction product can be predicted on the basis of the more or less electrophilic character of the two carbon atoms bearing R and R'.…”

Five‐Membered Heterocycles: 1,2‐Azoles. Part 2. Isoxazoles and Isothiazoles

“…This became an important route to 4-unsubstituted or 4-substituted isoxazoles bearing the same substituent at 3-and 5-positions. 4-Monosubstituted isoxazoles 62 and unsubstituted isoxazole 61 have also been prepared from the reaction of tetraalkoxypropanes (or b-dialdehydes) with hydroxylamine (Scheme 9.1) [6,10,84,85]. This route was applied to the synthesis of 3,5-disubstituted isoxazole-4-carbaldehydes using also diketones as the three-carbon building-block in the reaction with hydroxylamine [86].…”

“…The extensive studies on isoxazoles since the 1980s are due to their versatility in the synthesis of various compounds, namely heterocycles and natural products, as well as their applications in several fields, such as agriculture, medicine and industry [1,6,8,9]. In terms of the literature on isoxazole derivatives, one can find an enormous number of references on their chemistry, physicochemical and biological properties, as well as some book chapters (in Comprehensive Heterocyclic Chemistry, 1984 [10] updated in 1996 [8], and Science of Synthesis [11][12][13]) and monographs (Isoxazoles and Related Compounds, published in 1962 by Quilico [14] and Isoxazoles -Part 1 and Part 2, published in 1991 [6] and 1999 [9] by Gr€ unanger and VitaFinzi) which collate all this information. Part 1 of the last monograph is restricted to mononuclear isoxazoles and their hydrogenated derivatives (dihydroisoxazoles and tetrahydroisoxazoles), except for the isoxazolones, while Part 2 is devoted to the chemistry of condensed isoxazoles, namely benzisoxazoles and related compounds.…”

“…Benzisothiazoles are insoluble in water, but are soluble in strong acids (salt formation) and in organic solvents [6]. Table 9.4 shows the physical properties of unsubstituted compounds, isoxazole (1) and isothiazole (2), and their fused benzo-derivatives, 1,2-and 2,1-benzisoxazole (10) and (11) and 1,2-and 2,1-benzisothiazole (17) and (18), discussed in this chapter.…”

Synthesis of substituted 3‐phenyl‐6h‐pyrazolo[4,3‐d]isoxazoles from corresponding 4‐benzoyl‐5‐hydroxypyrazoles

“…A possible explanation for the failure of ring closure with 6d and 6e is the exclusive presence of these oximes in the 'wrong' (E)-configuration being not suitable for isoxazole ring formation (see NMR-spectroscopic investigations and Figure 1). It is well known that the configuration of the starting oximes plays a crucial role in such cyclization reactions [15,21,22]. Obviously, under the applied reaction conditions with 6d and 6e isomerisation to the corresponding (Z)-isomers does not occur, with only the latter species being anticipated to be suitable for cyclization into condensed systems 3.…”