1.2.4- Oxadiazoles hydrolysis

I-Cyano-3-phenylurea, first obtained by the alkaline hydrolysis of 5-anilino-3- -toluyl-l,2,4-oxadiazole, has been prepared by tlic condensation of phenyl isocyanate and the sodium salt of cyanamide. However, in these publications an incorrect structural assignment for the product was made. 1-Cyano-3-phenyl-urea is obtained also, together with other products, by warming gently l-cyano-3-phenylthiourea with caustic soda in the presence of ethylene chlorohydrin, or by gradually adding caustic )otash to a boiling solution of 1-phenyldithiobiuret and ethylene clilorohydrin in ethanol. ... 

The base and acid hydrolysis of. syrw-triazine mononitriles has been studied <06CHE642>. The potassium salt of 2-amino-4-methoxy-6-dinitromethyl-l,3,5-triazines 30 with N204 afforded the nitroformaldoximes 31 and the 1,2,5-oxadiazole iV-oxides 32 <06CHE1096> <06CHE557>. 

Access to oxadiazolopyrimidinium salts, for example, compound 93, was achieved via intramolecular electrophilic attack of the 2-nitrogen of the 1,2,4-oxadiazole 92 in the presence of HCIO4 (Equation 9). Competing reaction at N-4 also occurs and the products are often not isolated, but used as intermediates for hydrolysis, thereby producing pyrimidines <2006T1158>. 

As discussed previously, 1,2,4-oxadiazoles are generally considered to be resistant to hydrolysis <2001JCM209, 2004H01J(13)127>. However, extensive treatment of the 1,2,4-oxadiazole 104 (Equation 13) in DMF in the... 

The photolysis of 2-methyl-5-nitro-l//-imidazoles 132 in a water-containing solvent80 gives oxime 133, which is in turn hydrolysed to 134 followed by a dehydrative cyclization to the 1,2,4-oxadiazole 135. Light-induced hydrolysis of 135 gives 136 (equation 68). 

The chemistry of the 1,2,3-oxadiazole ring system is confined almost entirely to the mesoionic sydnones and related compounds. Sydnones are sensitive to hydrolysis, especially in basic media where they are rapidly cleaved. Nevertheless a range of useful reactions of sydnones, involving both ring cleavage and substitution with retention of the ring system, is known. Many of the publications that have appeared in the period 1982-1995 represent modifications or extensions to known reactions of sydnones. The subjects covered include the following. 

Oxadiazoles owe their importance mainly to their biological activities. A basic idea behind many developments is that the 1,2,4-oxadiazole ring is a hydrolysis resisting bioisosteric replacement for an ester functionality <90JMC1128,91JMC140,91QSAR109>. 

Phenyloxadiazole has been nitrated on the benzene nucleus without substitution occurring on the heterocycle. The hydrolysis of 3-nitrophenyl-oxadiazole has yielded a mixture of p. and m. nitrobenz-amide. 

The double bonds of the oxadiazole ring activate certain functional groups in the 5-position. For instance, when a keto group is in /S position, alkaline hydrolysis is facilitated as in the case of p diketones [50, 83, 95, 107,117), e.g. ... 

The hydrolysis or the reduction of 5-carboethoxyamino-oxa-diazoles yields the corresponding amino derivatives in good yields (61a). The synthesis starts from 5-carboethoxy-oxadiazoles and is carried out according to the following scheme ... 

However, hydrolysis of the oxime of 3-benzoyl-5-phenyl oxadiazole leads to benzoyl cyanamide (76). 

Trichloromethyl oxadiazoles can be prepared by the classical reaction from trichloracetamidoxime and acid anhydrides or chlorides. The trichloromethyl group is resistant under mild hydrolysis conditions such as hydrazine, ammonia or cold alkali treatment with boiling alkali leads to the salt of 3-carboxyoxadiazoles (see p, 845) 25a, 55b). 

Some relevant substituents are displayed in Table XV. Hydrolysis of esters or nitriles followed by thermal decarboxylation of 2-, 5-, 6-, and 7-carboxylic acids is often used for degradation reactions (61CPB883, 61JCS3046 64UP1). 5-Amino-l,2,4-triazole-3-carboxylic acid is decarbox-ylated in situ by condensation to TP (83S44) TP-5-amideoxime is cyclized to the 5-( 1,2,4-oxadiazol-3-yl) derivative (90EGP282009). 

Amino-l,3,4-oxadiazoles (205) on treatment with cr-halogeno-ketones gave intermediate quaternary salts 206 that did not cyclize directly to imidazo[2,l-6]oxadiazoles (208) with base. Hydrolysis of 206 with aqueous potassium carbonate caused ring-opening at C-2 with subsequent closure to the imidazolone 207. These latter compounds could be cyclized to 208 with phosphorus oxychloride.204c 21 246... 

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