Isoxazolium, 2-ethyl-5-

A. Carbobenzoxy-L-asparaginyl-L-lewine Methyl Ester. A mixture of 2.024 g. (0.0080 mole) of A -ethyl 5 phenylisoxazolium-3 -sulfonate [Isoxazolium, 2-ethyl-5-(3-sulfophenyl)-, hydroxide, inner salt] (Note 1) and 20 ml. of nitromethane (Note 2) is prepared in a 50-ml., glass-stoppered Erlenmeyer flask at room temperature and stirred vigorously... 

ISOXAZOLE, 3-(4-chlorophenyl)-5-(4-methoxyphenyl)-, 55, 39 Isoxazolium, 2-ethyl-5-(3-sulfophenyl)-, hydroxide, inner salt [4156-16-5], 56,88... 

Isoxazolidines, 58, 108 Isoxazolium, 2 ethyl 5 phen>l-3 -sulfonate, hydroxide, 56, 88... 

Isoxazolium, 2 ethyl-5-(4-sulfophenyl)-, hydroxide, inner salt, 56, 90... 

With the dicyclohexylcarbodiimide (DCQ reagent racemization is more pronounced in polar solvents such as DMF than in CHjCl2, for example. An efficient method for reduction of racemization in coupling with DCC is to use additives such as N-hydroxysuccinimide or l-hydroxybenzotriazole. A possible explanation for this effect of nucleophilic additives is that they compete with the amino component for the acyl group to form active esters, which in turn reaa without racemization. There are some other condensation agents (e.g. 2-ethyl-7-hydroxybenz[d]isoxazolium and l-ethoxycarbonyl-2-ethoxy-l,2-dihydroquinoline) that have been found not to lead to significant racemization. They have, however, not been widely tested in peptide synthesis. 

This isoxazolium salt (10 g.) (obtained from the Aldrich Chemical Company, Inc.) was dissolved in 45 ml. of aqueous 1 M hydrochloric acid and reprecipitated by the slow addition with swirling of 400 ml. of acetone. The salt was collected, washed with 300 ml. of acetone, and dried overnight at 25° under reduced pressure (< 1 min.) to give a fluffy product, m.p. 206-208° (decomp.). An isomeric salt, A-ethyl-5-phenylisoxazolium-4 -sulfonate, which may be obtained by the usual synthetic procedure,2 is also useful in peptide synthesis. 

Chances may be better, however, when a cyclic starting material includes the acyl group R4—CO. Here, the pathway based on Meldrum s acid was proven very useful [87JCS(P1)1177, 87TH1]. De Shong et al. started with R4-substituted isoxazoles (83JOC1149). The isoxazolium salts, obtained from ethyl bromoacetate, convert into /3-ketoamides, where best results were observed in two-phase systems. These /3-ketoamides cyclized to 3-acyI-tetramic acids by adding base. (See Fig. 13.)... 

Some reactions of 2,3,4-trisubstituted isoxazolium salts (exemplified by 70) leading to ring transformations, are summarized in Scheme 14.180 Other active methylene compounds such as ethyl acetoacetate and cyano-acetamide give analogous results to those with diethyl malonate products of base-induced ring opening by ethoxide are also obtained. When the reaction with phenylhydrazine is carried out in the presence of sodium hydroxide in ethanol the product is 71, presumably formed via the im-inoketene 72. 

C11H11N04S 2-ethyl-5-(3-sulfophenyl)isoxazolium hydroxi 4156-16-5 25.00 1.3355 2 21977 C11H13N02 DL-5-methyl-1,2,3,4-tetrahydroisoquinoline-3 151637-59-1 25.00 1.1775 2... 

Ethyl-5-(3-sulfophenyl)isoxazolium hydroxide, inner salt... 

Isoxazolium method, peptide bond formation using N-ethyl-5-phenylisoxazolium-3 -sulfonate (Woodward reagent K) forming an end ester with N-protected amino acids and peptides which reacts in situ with the amino component providing the desired product beside a water-soluble aryl sulfonate as a byproduct that is easy to separate [R. B. Woodward, R. A. Olofson. J. Am. Chem. Soc. 1961, 83,1010]. 

Pyrrolidinium acetate Piperidinium -Isoxazolium salts Trialky loxonium salt Amidinium salts Ketenimines Benzaldoxime Hy dr azobenzene Diazo compounds Diazomethane, Phenyl-diazomethane Ethyl diazoacetate K-methyldiazotate Hexamethylenetetramine Azo compds., Azobenzene Acylazo compds. Azodicarboxamide ROOC-N N-COOK Azodiisobutyronitrile Triazenes Diazonium fluoro-borates... 

Ethyl-5-(3-sulfophenyl)-isoxazolium hydroxide, inner salt Woodward s Reagent K C H N0,S 4156-16-5 253.275 dec 207 ... 

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