1.3.4- Oxadiazoles 2-amino- from

Examples include the synthesis of 3-amino-l,2,4-oxadiazoles starting from 3-acylamino-5-methyl-l,2,4-oxadiazole <2002H811> and 2-aryl-l,2,3-triazoles from l,2,4-oxadiazole-3-ketone arylhydrazones <1999T12885, 2006JOC5616>. Oximes, hydrazones, formamidines, and thioureas of the furazan series also undergo base-catalyzed mononuclear rearrangements <2004RCB1121>. Nucleophilic attack at N(3) takes place in the benzofuroxan series. For example, reaction with secondary amines leads to o-nitroarylhydrazines (Scheme 55). 

Early work of Stolle had indicated that oxidations of benzal-benzhydrazone (21) (also as the silver salt), usually by free halogen, give 2,5-diphenyl-l,3,4-oxadiazole. Apart from this, it has been almost exclusively the semicarbazones of aldehydes and of various a-keto acids that have been converted into 5-substituted 2-amino-... 

The same investigators illustrated an alternative protocol for the synthesis of 2-amino-l,3,4-oxadiazoles 104 from acylthiosemicarbazides 103 by employing IBX. Treatment of acylthiosemicarbazides with IBX-i-TEA combination promoted the cyclodesulfurization step to afford 2-amino-l,3,4-oxadiazoles in excellent yields. The acylthiosemicarbazides were easily prepared from the reaction of hydrazides 102 with various isothiocyanates 103 (Scheme 21) [37]. 

The 1,3,4-oxadiazole 113 is formed from the azo compound 112 by the action of triphenylphosphine <96SL652>. A general synthesis of 1,3.4-oxadiazolines consists in boiling an acylhydrazone with an acid anhydride (e.g., Scheme 18) <95JHC1647>. 2-Alkoxy-2-amino-l,3,4-oxadiazolines are sources of alkoxy(amino)carbenes the spiro compound 114, for instance, decomposes in boiling benzene to nitrogen, acetone and the carbene 115, which was trapped as the phenyl ether 116 in the presence of phenol <96JA4214>. 

Other non-traditional preparations of 1,2,3-triazoles have been reported. The rearrangement in dioxane/water of (Z)-arylhydrazones of 5-amino-3-benzoyl-l,2,4-oxadiazole into (2-aryl-5-phenyl-27/-l,2,3-triazol-4-yl)ureas was investigated mechanistically in terms of substituents on different pathways <06JOC5616>. A general and efficient method for the preparation of 2,4-diary 1-1,2,3-triazoles 140 from a-hydroxyacetophenones 139 and arylhydrazines is reported <06SC2461>. 5-Alkylamino-] //-], 2,3-triazoles were obtained by base-mediated cleavage of cycloadducts of azides to cyclic ketene acetals <06S1943>. Oxidation of N-... 

A direct catalytic conversion of esters, lactones, and carboxylic acids to oxazolines was efficiently achieved by treatment with amino alcohols in the presence of the tetranuclear zinc cluster Zn4(0C0CF3)60 as catalyst, essential for condensation and cyclodehydration reactions. For example, the use of (5)-valinol allowed the easy synthesis of oxazolines 125 and 126 in satisfactory yields <06CC2711>. A one-pot direct preparation of various 2-substituted oxazolines (as well as benzoxazoles and oxadiazoles) was also performed from carboxylic acids and amino alcohols (or aminophenols or benzhydrazide) using Deoxo-Fluor reagent <06TL6497>. 

Each of the routes discussed thus far in this section are reliant upon amidoxime-based methods. In a change from this paradigm, Makara etal. produced the polymer-supported benzotriazoles 294 and converted them easily into the iV-acyl-177-benzotriazole 1-carboximidamides 295. Cyclization with hydroxylamine gave the supported 3-amino-l,2,4-oxadia-zoles 296 which were cleaved with TFA to give the free 3-amino-l,2,4-oxadiazoles 297 (Scheme 49) <2002TL5043>. 

Dimerization of nitrile oxides derived from 4-amino- and 4-R-substituted l,2,5-oxadiazole-3-carbohydroximoyl chlorides 201 leads to the formation of tricyclic furoxans 200 or compound 202 (Scheme 45) <2001RJ01355>. 

In the presence of bis(acetylacetonato)nickel, a-dicarbonyl compounds readily add at the nitrile group of 4-R-substituted l,2,5-oxadiazole-3-carbonitriles 219 to form enaminofurazans 220. The adducts obtained from 4-amino-3-cyanofurazan underwent intramolecular cyclization upon heating with acetic acid in ethanol to give furazano[3,4- ]pyridine 221 derivatives in high yields (Scheme 51) <2001RCB1280>. 

Two variations of the transformation of 3-acyltetrazoles into oxadiazoles are useful from a synthetic point of view. The first transformation involves the reaction of tetrazole with diketene. In the second, the sodium salt of the tetrazole is treated with oxalyl chloride. UV irradiation of some 3-amino-l,2,4-oxadiazoles leads to the formation of the corresponding 2-amino-l,3,4-oxadiazoles <1996CHEC-II(4)268>. 

Dipolar cycloaddition of nitrile oxide at the C=N bond of indole imino esters 130, followed by elimination of the alcohol moity gives oxadiazole derivatives 131 (Scheme 1.26) (298). Reaction of N-arylbenzamidines with arenenitrile N-oxides (generated in situ from oximoyl chlorides) produce unstable 5-amino-4,5-dihydro-1,2,4-oxadiazoles which, on aqueous acidic treatment hydrolyze to open-chain N-benzoyloxy-N -arylareneamidines (299). 

Heterocyclic ring systems are also used to connect two anthraquinone groups. Typical examples include Cl Vat Red 10 (6.106), which is an oxazole derivative obtained from 2-amino-3-hydroxyanthraquinone and the appropriate acyl chloride, the similar thiazole derivative Cl Vat Blue 31 (6.107) and the oxadiazole derivative Cl Vat Blue 64 (6.108). 

Corresponding electron-transport materials have been made by replacing the amino substituents in the first shell by oxadiazole groups (29) [70, 61] or phenyl-quinoxalines (30) [60]. As in the case of the amines, dendrimer-shaped structures are obtained by repeating the substitution pattern in a second shell (31) [76], The Tg was increased from 142°C in 29 to 222° C in 31. 

From Other Heterocyclic Systems 4-Arylazoisoxazoles can rearrange to 2-aryltriazoles, and 4-amino-2//-triazoles can be prepared by reaction of 4-nitrosoimidazoles with hydrazines (Scheme 34). The hydrazones of 3-benzoyloxadiazoles are intermediates in the latter reaction.The generality of rearrangements of this type has been discussed, and a further example, involving the rearrangement of a 1,2,5-oxadiazole to a triazole, has been described. 

Amino-1,2,3-triazoles with a substituent at the 4-position have been prepared (i) from azides and active methylene nitriles (ii) from azides and ynamines (iii) from diazomethane and carbo-diimides (iv) from azides and 1,1-diaminoethenes and (v) from the rearrangement of 3-hydrazono-1,2,4-oxadiazoles. Among these, the first method, a regiospecific process, is the most versatile and convenient although it is suitable only for 5-NH2-substituted triazoles. Other methods are used to prepare 5-NHR , 5-NR R - and 5-NHCOR-substituted triazoles. Intramolecular cyclization of suitable precursors also gives 5-aminotriazoles. For example, a-imino-a-piperidyl phenylhydrazones (838), in the presence of copper acetate, give 5-piperidyl-triazoles (839) (Equation (85)) <94H(38)739>. 

Routes to benzoxadiazoles are based on approaches to the tautomeric 6-diazo-2,4-cyclo-hexadienones (Scheme 11) <9UST(247)135>. The appropriate 2-aminophenol hydrochloride is diazo-tized using either sodium nitrite or isoamyl nitrite and the diazonium chloride is then carefully neutralized with sodium carbonate or potassium carbonate. An alternative approach is from the monotosylhydrazone of the appropriate o-benzoquinone. Naphthoxadiazole (6) was prepared, in a manner analogous to the first route of Scheme 11, from 3-amino-2-naphthol <91AG(E)1476>. A slightly modified preparation is described in a later paper the method was applied to the synthesis of [9a- C]naphth[2,3-( ]-l,2,3-oxadiazole from 3-amino-[2- C]-2-naphthol <92Mi 403-03>. 

Graubaum and Martin isolated the acetylhydrazino thiatriazole (142) in approximately 50% yield from the reaction of 5-hydrazinothiatriazole (133) with acetic anhydride <85ZC136>. On heating to 40 °C, (142) extruded nitrogen and sulfur to give 2-amino-5-methyl-1,3,4-oxadiazole (143) (Scheme 29). 

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