Synthesis from Acylhydrazines

Synthesis from Acylhydrazines. The condensation of acyl hydrazines and ethyl dithioacetate in boiling ethanol furnishes 5-aryl-2-methyl-l,3,4-thiadiazoles, but 1,3,4-oxadiazoles are formed as main products in some cases. Under suitable conditions, the intermediate thioacetylacylhydrazines may be isolated.  

Synthesis from -Thiocyanato-2,i diazabuta-, 3-dienes. l-Chloro-l,4-di-phenyl-2,3-diazabuta-l,3-diene (113) is readily converted by potassium thiocyanate into the corresponding 1-thiocyanato-compound (114) from which 1,3,4-thiadiazoles may be obtained. Thus, thermolysis of (114) in boiling toluene produces, in addition to much polymeric material (53%), 

2-benzylideneamino-5-phenyl-l,3,4-thiadiazole (116) (47%) by a mechanism possibly involving the intermediate (115). Acid hydrolysis of (114) produces benzaldehyde and 2-amino-5-phenyl-l,3,4-thiadiazole (117) directly (94%).  

Anthoni, C. Larsen, and P. H. Nielsen, Acta Chem. Scand., 1970, 24, 179. 

Synthesis from l,2-Dithiole 3-thiones. 5-Aryl-l,2-dithiole-3-thiones (118) react with a-chlorobenzylidenephenylhydrazine (119), with simultaneous dithiole-ring opening and formation of (A -l,3,4-thiadiazolin-2-ylidine)-thioacetophenones (120). The use of ethyl bromo(phenylhydrazono)-acetate similarly affords (5-ethoxycarbonyl-3-phenyl-A -l,3,4-thiadiazolin-2-ylidene)thioacetophenone, which is saponifiable to the corresponding 5-carboxylic acid. The reactions resemble Huisgen s synthesis of iV-(3,5-diphenyl-A -l, 3,4-thiadiazolin-2-ylidene)benzamide from (119). 

---

Substituted acylhydrazones (95), formally derivatives of 1,2-diacylhydrazines (75), also cyclize to oxadiazoles (76), with loss of HX. Imidol ethers (95a R2 = H), prepared from acylhydrazines R1CONHNH2 and ortho esters HC(OR)3, cyclize on heating to monosub-stituted oxadiazoles (76 R1 = H). This reaction is an important synthesis of monosubstituted... 

Examples of syntheses from three-membered heterocycles are the synthesis of the oxadiazolylpropylamine (122) from acylhydrazine ArCONHNH2 and 3,3-dimethyl-2-dimethylaminoazirine (78HCA2419), and the conversion of 3,3-dialkyldiaziridines into oxadiazolines (123) on heating above 150 °C with an anhydride (R3C0)20 (76MIP42300). 

Closely related are the syntheses from various sulfur-containing derivatives of 2-pyridylhydrazine by which it is possible to obtain the 3-thiol (or thione) 6180 or 3-methylaminotriazolopyridine (62).88 By use of dithio-carbamates instead of acylhydrazines, the iminoether synthesis gives the tetrahydrotriazolopyridine-3-thiol (or thione) 63.89-92 Cyclization of the amidine 64 gives 3-anilinotriazolopyridine (65).93... 

Synthesis of l,2,4-triazolo[l,5-c]quinazolines from nonquinazoline intermediates is also known. Thus, the two heterocyclic rings were formed by the reaction of acylhydrazines with 2-ureidobenzonitriles (89JPR-537), 2-ethoxycarbonylaminobenzonitriles (329) (87USP4713383), or 2-isocyanatobenzonitrile (87CZ373) to give the title compounds (e.g. 330). 

Treatment of acylhydrazines with diazonium salts gives rise to tetrazenes (199) which can be readily dehydrated with base to give 1,5-disubstituted tetrazoles (Scheme 33). The reaction is also effective with 1,2-diacylhydrazines since one of the acyl groups is cleaved during the dehydrative cyclization, which may be conveniently carried out in situ without isolation of the tetrazene. This reaction can be useful for the synthesis of 1-aryltetrazoles using 1,2-diformylhydrazine as substrate (B-67MI41300). Mesoionic tetrazolium 5-oxides (8a) are obtained on treatment of bis(alkylsulfonyl)methanes with diazonium salts. Hydra-zones of type (200) are also obtained from these reactions and the tetrazenes... 

Acid amide-triphenylphosphine dihalide adducts (4) have found wide application in organic synthesis. - Synthetic equivalents are adducts (5) from acid amides and triphenylphosphine/CCU, which are prepared in situ from the educts. - With these reagents the following transformations have been performed dehydration of amides or aldoximes to nitriles, preparation of isonitriles from secondary form-amides, preparation of imidoyl halides from amides or acylhydrazines and preparation of ketene imines from amides. Using polymer-supported triphenylphosphine the work-up procedure is much easier to achieve. Triphenylphosphine can be replaced by tris(dialkylamino)phosphines. - Instead of CCI4 hexa-chloroethane, hexabromoethane or l,l,2,2-tetrabromo-l,2-dichloroethane can be used " the adducts thus formed are assumed to be more effective than those from the triphenylphosphine/CCU system. 

---