Isoxazole, 4-amino-3,5-dimethyl

The enthalpy of combustion of isoxazole was only determined several years ago (78MI41615). For isoxazole, AH°c (298.15 K) =-(1649.85 0.50) kJ mol , from which the entropy of formation in the gas phase was derived as AH tig) = 78.50 0.54 kJ moF. The enthalpies of combustion of 3-amino-5-methylisoxazole and 5-amino-3,4-dimethyl-isoxazole have also been determined (73MI41606). 

In contrast to the 3-substituted products above, 4-chloro-, 4-bromo- and 4-iodo-isoxazoles are readily prepared by direct halogenation of the corresponding isoxazoles, from 4-isoxazolediazonium salts by the Sandmeyer reaction, or by reaction of hydroxylamine with a-halo- 8-dicarbonyl compounds (62HC(l7)l, p. 66, 63AHC(2)365). 3,5-Bis(dimethyl-amino)-4-fluoroisoxazole has been synthesized by reaction of (Me2NCO)2CHF with hydroxylamine (78BSB391). 

Dimethindene maleate -Dimethylaminoethyl mercaptan HCI Echothiopate iodide Dimethylaminoisopropyl chloride Isothipendyl HCI 3,4-Dimethyl-6-amino isoxazole Sulfisoxazole... 

Under conditions of thermolysis, photolysis and hydrogenation certain isoxazoles can be converted into imidazoles. For example, merely heating 5-amino-3,4-diaUcylisoxazoles at 180-190°C gives 40-65% yields of 4,5-dialkylimidazolln-2-ones in what initially appears to be a Dimroth-type rearrangement. Compounds such as 4-mcthyl-5-propyl-, 4-butyl-5-propyl, 5-benzyl-4-methyl-, 4,5-dimethyl- and 4-ethyl-5-methylimidazoles can be formed in the same way, but only if urea is present and if the reaction is carried out in the condensed phase. Without the added urea (or an arylamine) the yields are only 40-65% with urea they reach 70-90% [29-31]. 

Tetramethylpyrazine was also formed in low yield from 5-amino-3,4-dimethyl-isoxazole and semicarbazide in ammonia (307) and 4,5-diethoxycarbonyloxazole in glycol with a little sulfuric acid at 100° gave 2,3,5,6-tetraethoxycarbonyl-pyrazine (267). 

Various other heterocycles have also been converted to pyrazines. Thus tetra-phenylpyrrole with lead tetraacetate and potassium carbonate in chloroform has been shown to give a 20% yield of tetraphenylpyrazine (498) 5-amino-3,4-dimethyl-isoxazole (117) and 50% hydrazine hydrate, when heated on a water bath and the product treated with hot concentrated hydrochloric acid, pve tetramethylpyrazine (499). Treatment of 3-amino-24iydroxy-4,4-dimethyltetrahydrofuran (118) with strong alkali gave 2,5-bis(hydroxy-f-butyl)pyrazine (119) (500) and catalytic hydrogenation of furylamines (120) over platinum at 220-225° gave alkylpyrazines (121) (500a). 

This dimer reacts as two molecules of free 5- alkyli-soxazolyl-3-isocyanate with secondary amines or with alcohols to give the corresponding ureas or carbamates useful as agrochemicals or fine chemicals intermediates. For example, 3-amino-5-tert-butyl isoxazole is a key intermediate for 3- 5-tert-butylisoxazolyl)-1,1-dimethyl urea (common name Isouron) which is useful as a herbicide for sugar cane and other crops (Ref. 180) [Scheme 127]. 

Isoxazoles. - Formation. The combined action of copper(II) nitrate and acetic anhydride on 1,2-diphenylcyclopropane leads to a mixture of 3,5 diphenylisoxazole and its 4-nitro-derivative. Dimethyl azidomaleate affords the azirine (324) on heating, whereas the azidofumaric ester yields the isoxazole (325). 5-Amino-4-ethylthio-3-methylisoxazole (326) is produced from the acrylonitrile derivative MeCBr=C(SEt)CN and hydroxyl-amine." ... 

It is prepared by condensing together / -acetamidobenzene sulphonyl chloride (ASC) with 5-amino-3,4-dimethyl isoxazole and hydrolysing the resulting product in an alkaline medium. 

Reaction of A-protected diethyl aspartate (130) or glutamate (131) with lithium trialkylphosphonoacetate in the presence of DIBALH leads to selective formation of the A-protected y-amino-a,P-unsaturated dicarboxylates (132) as the major product. 3-(Phosphonomethyl)cyclo-pentenones (133) and -hexenones (134) are the products of the reaction of dimethyl succinate and dimethyl glutarate, respectively, with excess dimethyl (lithiomethyl)phosphonate presumably via two phosphonomethylations followed by an intramolecular olefmation. Examples of the many phosphonate olefmation reactions carried out include the synthesis of (2E, 4Z)-4-aminoalkadienoates (135), 2-aryloxy-3-phenylpropenoates (136), and isoxazoles (137). ... 

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