1.2.4- Triazolin-3-ones

Acyl hydrazides are useful precursors for the synthesis of 1,2,4-triazoles. Reaction of acyl hydrazides 149 with imidoylbenzotriazoles 148 in the presence of catalytic amounts of acetic acid under microwave irradiation afforded 3,4,5-trisubstituted triazoles 150 <06JOC9051>. Treatment of A-substituted acetamides with oxalyl chloride generated imidoyl chlorides, which reacted readily with aryl hydrazides to give 3-aryl-5-methyl-4-substituted[ 1,2,4]triazoles <06SC2217>. 5-Methyl triazoles could be further functionalized through a-lithiation and subsequent reaction with electrophiles. ( )-A -(Ethoxymethylene)hydrazinecarboxylic acid methyl ester 152 was applied to the one-pot synthesis of 4-substituted-2,4-dihydro-3//-1,2,4-triazolin-3-ones 153 from readily available primary alkyl and aryl amines 151 <06TL6743>. An efficient synthesis of substituted 1,2,4-triazoles involved condensation of benzoylhydrazides with thioamides under microwave irradiation <06JCR293>. 

Treatment of l-benzoyl-6-methyl-l,6-dihydro-l,2,4-triazine-3,5-dione (126) with bases led to the 5-phenyl-1,2,4-triazolin-3-one (127) (03JA386). 

Synthesis of l,2,4-Triazolin-3-ones. The use of TMS-Br in the formation of carbo- and heterocycles is well known. A further example of this type of chemistry is the preparation of 1,2,4-triazolin-3-ones. Thus, when an iV-formylsemicarbazide is treated with TMS-Br in the presence of hexamethyldisilazane (HMDS) and catalytic ammonium sulfate activation takes place followed by cyclization (eq 43). The HMDS acts as both solvent and silylating agent for this reaction. After cyclization is achieved the reaction is completed by loss of bis-TMS ether. The nature of the... 

N-methyl-No structure propoxy available triazolin-one amide... 

There is a drive to develop insensitive or less sensitive munitions, ie, those less likely to accidental or sympathetic detonation. A leading candidate is 3-nitro-l,2,4-triazolin-5-one [930-33-6] (59), made by the reaction of semicarbazide and formic acid to give l,2,4-triazolin-5-one [932-64-9] foUowed by nitration of the triazolone (218). 

No definite choice between the two tautomeric forms was made in early studies of 5-mercapto-l,3,4-triazolin-2-one 244 (Scheme 84) [76AHC(S1), p. 464]. The oxo-thione form 245, similar to 241, was attributed to 2-mercapto-4-hydroxyoxazole and its derivatives based on IR-spectro-... 

Certain facts in the urazole series can also be interpreted in this way. Urazole (17) itself reacts with diazomethane quickly to yield 4-methyl-3-methoxy-l,2,4-triazolin-5-onc (18), which is more slowly converted to l,4-dimethyl-3-methoxy-l,2,4-triazolin-5-one (19). 1-Phenylurazolc gives 4-methyI-3-mcthoxy-l-plicnyl-l,2,4-triazolin-5-one (20) however, 4-phenylurazole yields the 1,2-dimethyl derivative (21). In the case of 4-methylurazole both O- and A"-methylation... 

Normal reactions are found again for systems containing C=N double bonds. An unstable triazoline is probably an intermediate product in the reaction of pteridin-7-one (117)to give a mixture of the 8-methyl (118) and 6,8-dimethyl derivatives (119). C-Methylation also occurs in the case of quinoxalin-2-one. ... 

Intramolecular dipolar azide-olefin cycloaddition of 723 took place upon heating in benzene to afford 724 (83JA3273). An alternative rearrangement process can take place upon photolysis of 724 to give 725. Mesylation of 4-(3-hydroxypropyl)-2,4,6-trimethyl-2,5-cyclohexadiene-l-one (78JA4618) and subsequent treatment with sodium azide in DMF afforded the respective azide 726 which underwent intramolecular cycloaddition to afford the triazoline 727 (83JOC2432). Irradiation of 727 gave the triazole derivative 728 (Scheme 126). 

Azides add to double bonds to give triazolines. This is one example of a large group of reactions ([3-l-2]-cycloadditions) in which five-membered heterocyclic compounds are prepared by addition of 1,3-dipolar compounds to double bonds (see Table 15.3). These are compounds that have a sequence of three atoms A—B—C,... 

Two heterocyclic phosphonates have been designed and synthesized in an attempt to identify more spatially conHned, planar analogs of glyphosate than obtained previously with the pyridine analog 111 (75). Molecular modeling experiments suggest that 5-phosphono-thiazolin-2-one 133 and 5-phosphono-l,2,4-triazolin-3-one 137 each may overlap either with glyphosate or its known competitive substrate, phosphoenolpyruvate (PEP), very well (5). 

The synthesis of 5-phosphono-l,2,4-triazolin-3-one 137 began with the low-temperature metalation and phosphorylation (77) of the f-butyldimethylsilyl (TBDMS)-protectedlV-benzyl-tiiazolinone 134. The phosphonate diester 135 was obtained ter the silyl protecting group... 

Dipolar cycloaddition of pyrido[2,l-A][l,3]thiazinium betaine 507 (R = Me) with 1-diethylamino-l-propyne afforded cycloadduct 508, from which quinolizin-4-one 509 formed by a rapid cheletropic extrusion of COS (Scheme 53) <1995T6651>. 1,4-Dipolar cycloaddition of 507 and 4-phenyl-l,2,4-triazoline-3,5-dione yielded 511 (via 510) <1995H(41)1631> and 512 <1995T6651>. 

A different result was obtained in the cycloaddition to methylenecyclo-propanes 216-218 tearing alkoxycarbonyl substituents on the cyclopropyl ring. In this instance, 1,2,3-triazoles 220 isomeric with the triazolines 219 were formed in the reaction [57]. The formation of triazoles 220 is rationalised by the intermediate formation of triazolines 219, which are unstable under the reaction conditions and undergo a rearrangement to the aromatic triazoles via a hydrogen transfer that probably occurs with the assistance of the proximal ester carbonyl (Scheme 35). The formation of triazoles 220 also confirms the regio-chemistry of the cycloaddition for the methylene unsubstituted methylene-cyclopropanes, still leaving some doubt for the substituted ones 156 and 157. 

Spiro[3H-indole-3,5(4.H)-(l,2,4)triazoline]-2-one derivatives 204 have been obtained using microwave irradiation in the reaction between imines of isatin 203 and nitrile imines generated in situ from the corresponding hydrazonyl chlorides 199 (Scheme 9.63). The yields are in the range 85-95% and the reaction is complete within 5 min [110]. Similar reactions performed under thermal conditions were complete in 6-10 h and yields decreased to 20-30%. However, when the reaction was performed at ambient temperature, the products were obtained in excellent yields but only after a prolonged reaction time (30 h). 

Cycloaddition reactions of dimethyl benzylidenemalonate 262 with azides provide triazolines 263. All compounds 263, except one with R = Ph, are stable in xylene at 110 °C. The phenyl derivative eliminates molecular nitrogen to give dimethyl l,3-diphenylaziridine-2,2-dicarboxylate 264. At elevated temperature, the aziridine system is not... 

The irradiation of 5-amino-l,2,4-oxadiazoles 60 in the presence of nucleophilic nitrogen sources (primary amines, ammonia or hydrazine) produced l,2,4-triazolin-5-ones 62, a process which proceeds via cleavage of the N-O bond and addition of the nucleophile to form the intermediate 61 (Scheme 3) <1996JOC8397>. 

When, phenylazide and 3-methyl-1-butene are mixed in benzene and kept standing for a couple of days, triazoline is formed and it gives aziridine by thermal or photodecomposition. However, when the mixture is irradiated as soon as they are mixed, the aziridine which is found in the solution is the one formed, not by the decomposition of the triazoline but, by direct photochemical reaction of phenylnitrene with 3-methy1-1-butene. 

Imines derived from ketones with an a-methylene group can react via their enamine tautomers, and mixtures of triazoles are also isolated from these systems. The triazoline adducts of the enamine tautomers are aromatized by treating with acid, and in these conditions the triazoline appears to undergo a Dimroth rearrangement before elimination of the amine, because two triazoles are obtained, one of which has... 

Treatment of the alcohol ( ) with trifluoromethylsulfonic anhydride (triflic anhydride) at -78 C afforded the ester (1 ) which could be isolated and characterized. We knew from previous experience (2J that sulfonyl esters vicinal to an isopropylidene acetal are relatively stable. The triflate T,) reacted cleanly with potassium azide and 18-crown-6 in dichloromethane at room temperature. The crystalline product [68% overall from (1 )] was not the azide ( ) but the isomeric A -triazoline ( )- Clearly the initially formed azide (18) had undergone intramolecular 1,3-cyclo-addition to the double bond of the unsaturated ester (21- ). The stereochemistry of the triazoline (1 ), determined by proton nmr spectroscopy, showed that the reaction was stereospecific. There are several known examples of this reaction ( ), including one in the carbohydrate series ( ). When the triazoline was treated with sodium ethoxide ( ) the diazoester ( ) was rapidly formed by ring-opening and was isolated in 85% yield, Hydrogenolysis of the diazo group of (M) gave the required pyrrolidine ester ( ) (90%). 

The base-catalyzed rearrangement of oxadiazolylureas 184 into ben-zoylamino-l,2,4-triazolin-5-ones 185 has been mechanistically examined by using amines as catalysts in acetonitrile and benzene, and borate buffers at various pS in dioxan-water [90JCS(P2)1289]. For the piperidine-... 

Under these conditions only one mixed [6,6]-triazoline-azahomofullerene isomer 25 was formed, which is explained by the fact that 24 behaves as a strained electron-poor vinylamine. The significantly highest Mulliken charge of 0.06 (AMI) is located at C-1 and C-6, and the lowest of-0.07 at C-2 and C-5 (Figure 10.10). The most negatively polarized N atom of the azide (AMI) is that bearing R. A kinetically controlled attack of the azide, therefore, leads predominantely to 25. 

The syntheses have been reported of la,3/3-dihydroxy-4,4-dimethylcholesta-5,7-diene (269) and its 3a-epimer, along with the ergostane analogues/ As reported in the preliminary account, 4,4-dimethylcholesta-5,7-dien-3-one underwent the ene reaction with 4-phenyl-1,2,4-triazoline-3,5-dione to give (270) rather than the normal Diels-Alder adduct.Treatment of (270) with acid gave the trienone (271). Treatment of cholecalciferyl tosylate with aq. KHCO3-... 

---