Carboxylic acid hydrazides 1,3,4-Oxadiazoles

Bisoxadiazoles are formed from bis(mono)imido ester hydrochlorides and mono(bis)carboxylic acid hydrazides when the free ester is used, an amidrazone (27) is often formed which cyclizes with the elimination of ammonia to give 28.73 The reaction proceeds in the presence of higher boiling solvents or by mixing the reactants at a temperature higher than 100°, the imido esters forming first in the reaction mixture. The reaction of semicarbazide [Eq. (2), R = NH2] with imido esters does not, of course, lead to 2-amino-1,3,4-oxadiazoles but to the isomeric l,2,4-triazolin-3-ones.72 The reaction of N-substituted imidochlorides with aromatic acid hydrazides in the... 

Reactions with mercaptoformamide chloride 1,3,4-Oxadiazoles from carboxylic acid hydrazides... 

Periluoroalkyl-1,2,4-triazoles are often formed by rearrangement of other heterocycles or by cyclization of carboxylic acid hydrazides or their analogues. In 1962 Brown and Cheng described for the first time the synthesis of 3,5-bis(perfluoroaIkyl)-l,2,4-triazoles 70 by treatment of bis(perfluoroaIkyl)-1,3,4-oxadiazoles with methylamine [71], The method for the synthesis of NH-unsubstituted 3,4-bis(perfluoropropyl)-l,2,4-triazole by the action of P2O5 on the corresponding hydrazine was also reported in this paper. Thirty years later Threadgill et al. [72] prepared 3,5-bis(trifluoromethyl)-4-(3-benzyloxypropyl)-4H-1,2,4-triazole by the reaction of 2,5-bis(trifluoromethyl)-l,3,4-oxadiazole with 3-benzyloxypropylamine in methanol (reflux, 9 days). 

Carboxylic acid hydiazides are prepared from aqueous hydrazine and tfie carboxylic acid, ester, amide, anhydride, or halide. The reaction usually goes poody with the free acid. Esters are generally satisfactory. Acyl halides are particularly reactive, even at room temperature, and form the diacyl derivatives (22), which easily undergo thermal dehydration to 1,3,4-oxadiazoles (23). Diesters give dihydtazides (24) and polyesters such as polyacrylates yield a polyhydrazide (25). The chemistry of carboxyhc hydrazides has been reviewed (83,84). 

Electrophilic substitution of the ring hydrogen atom in 1,3,4-oxadiazoles is uncommon. In contrast, several reactions of electrophiles with C-linked substituents of 1,3,4-oxadiazole have been reported. 2,5-Diaryl-l,3,4-oxadiazoles are bromi-nated and nitrated on aryl substituents. Oxidation of 2,5-ditolyl-l,3,4-oxadiazole afforded the corresponding dialdehydes or dicarboxylic acids. 2-Methyl-5-phenyl-l,3,4-oxadiazole treated with butyllithium and then with isoamyl nitrite yielded the oxime of 5-phenyl-l,3,4-oxadiazol-2-carbaldehyde. 2-Chloromethyl-5-phenyl-l,3,4-oxadiazole under the action of sulfur and methyl iodide followed by amines affords the respective thioamides. 2-Chloromethyl-5-methyl-l,3,4-oxadia-zole and triethyl phosphite gave a product, which underwent a Wittig reation with aromatic aldehydes to form alkenes. Alkyl l,3,4-oxadiazole-2-carboxylates undergo typical reactions with ammonia, amines, and hydrazines to afford amides or hydrazides. It has been shown that 5-amino-l,3,4-oxadiazole-2-carboxylic acids and their esters decarboxylate. 

As in Section 5.06.9.1, the assignments are sometimes arbitrary. Important routes to oxadiazoles, aminooxadiazoles, oxadiazolinones, and oxadiazolinethiones involving the reaction of hydrazides RCONHNH2 with carboxylic acids, acyl chlorides, alkyl esters, or trialkyl orthoesters are described in Section 5.06.9.2.1, reactions with carbon disulfide... 

The reactions of hydrazides with the respective carboxylic acids afforded oxadiazole derivatives 123 <1996JME2753>, 124 <2000BML1645>, 125 <2003JFC163>, and 126 <2004EJM535>. The reactions... 

A one-step synthesis of 1,3,4-oxadiazoles from readily available carboxylic acids and acid hydrazides was mediated by the polymer-supported reagent... 

Ring cleavage of the 2,5-dialkyl-1,3,4-oxadiazoles by either acid or base leading to carboxylic acids and hydrazine or acid hydrazides [Eq. (14)] has been known for some time.1 Investigation of the... 

Li et al. [30] gave the solvent free synthesis of 2-aryl-5-(coumarin-3 -yl)-l,3,4-oxadiazoles (xxv) in high yields by reacting the coumarin-3-carboxylic acid (xxiii) with (un)substituted benzoic acid hydrazides (xxiv) in presence of PEG supported dichlorophosphate under microwave irradiation. 

The synthesis of 5-aryl-2-(2-hydroxyphenyl)-l,3,4-oxadiazoles (xL) reacting salicylic hydrazide (xxxix) with carboxylic acids in the presence of thionyl chloride under neat conditions is described [37]. 

Recently, Demirba reported preparation of 3,6-di[(4,5-dihydro-l,2,4-triazol-l-yl)methyl]-l,4-dihydro-l,2,4,5-tet-razines 2a-e by heating of equimolar mixtures of ([l,2,4]triazol-l-yl)acetohydrazides 65a-e and carboxylic acids 66 at 130-140 °C. Formation of 1,2,4,5-tetrazines 2a-e was quite unexpected, since more stable 1,3,4-oxadiazoles or 1-amino-l,2,4-triazoles could also be formed. However, the hydrazides 65a-e did not react with the carboxylic acid 66 and underwent cyclocondensation with another molecule of hydrazide 65a-e, respectively, to furnish the corresponding tetrazines 2a-e (Scheme 16) <2004MI311>. 

The hydrazide of benzothiazole-2-carboxylic acid may be converted into compounds [1 R = C(0)NHNHC(O)Alk, C(0)NHNHC(0)Ar, C(0)NHNH-C(0)NHAlk, C(0)NHNHC(S)NHAlk, or C(0)NHNHC(S)NHAr] by standard procedures. Cyclization of the oxygen compounds with polyphosphoric acid or phosphorus oxychloride, or of the sulphur compounds with red lead or iodine in sodium hydroxide, yields the corresponding 1,3,4-oxadiazole (37 X = O). The 1,3,4-thiadiazoles (37 X = S) may be prepared by treatment of the oxygen compounds with phosphorus pentasulphide or by cyclization of the sulphur compounds with acid. Compounds (38 X = O or S Y = N) may be prepared similarly from benzothiazole-6-carboxylic acid. When compounds [1 R = C(0)NHNHC(S)NHAlk or C(0)NHNHC(S)NHAr] are cyclized with 5% aqueous sodium hydroxide or polyphosphoric acid they yield compounds (37 ... 

In the belief that the gastric irritation produced by salicylates may be partly due to the free carboxyl group. Smith, Frommel and Radouco-Thomas prepared the corresponding hydrazide XIX) and oxadiazol-2-ol XX) of salicylic acid. 

Oxadiazoles 8 [465] are obtained by acid-promoted cyclocondensation of carboxylic hydrazides (acylhydrazines) (a) with acid chlorides in the presence of P4O10 [466] and (b) with orthoesters catalyzed by alum (KA1(S04)2 12 H2O) [467] ... 

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