1.2.4- triazolin-5-ones synthesis

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... 

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>. 

The first synthesis of the parent compound of the benzo[4,5]thieno[2,3-f]pyrrole ring system 387 <2003T1477> and its derivatives was accomplished using the same synthetic sequence (Scheme 42). Starting with 2-methyl-benzo[ ]thiophene-3-carbaldehyde 388, an intermediate 389 was obtained. Treatment of bromo compound 389 with sodium azide in ethanol led to the stable triazoline 390. 1,3-Dipolar cycloreversion of 390 was induced by a catalytic amount of />-TsOH to give the parent 2//-benzo[4,5]thieno[2,3-c]pyrrole 387. Alternatively, direct treatment of bromo compound 389 with excess ammonia furnished 387 in one step. Compound 387 was treated with di-/-butyl dicarbonate and 4-dimethylaminopyridine (DMAP) to give iV-BOC derivative 391. Reaction of 389 with... 

Irradiation of triazolines with UV light of k > 240 nm, the region of maximum absorption, constitutes one of the principal methods for the synthesis of various substituted aziridines.79 "3 The photolysis reaction is essentially independent of substituent and solvent effects in some cases aziridines are accompanied by imines.79... 

A number of other five-membered ring nitrogen heterocycles have been prepared by cyclative cleavage. The illustrative examples (Fig. 4) depict the synthesis of pyrazolones,12 succinimides and phthalimides,13 pyrrolo[3,4-h] pyridines,14 2-aminoimidazolones,15 imidazo[4,5-fr]pyridin-2-ones,16 and l,2,4-triazoline-3,5-diones.17... 

Aminoquinolines 62 have been prepared in a two-step, one-pot, three-component reaction of 2-azidobenzophenones, secondary amines and arylac-etaldehydes [110]. The microwave-assisted reaction proceeded via the initial formation of enamines 59. Subsequent addition of 2-azidobenzophenones 60 afforded the triazoline intermediates 61, which underwent thermal rearrangement and cyclocondensation to furnish 2-aminoquinolines 62 (Scheme 41). Direct comparison with conventional thermal conditions demonstrated the superiority of microwave dielectric heating in terms of yields (73% vs. 31% of heterocycle 63 after 10 min at 180 °C). Furthermore, the formation of by-products due to decomposition of azide 60 was diminished in the microwave-assisted synthesis. Purification of the products was achieved using solid-phase extraction techniques. 

Irradiation of the 5,7-diene gave the previtamin, which was isomerized and saponified to give la-hydroxy-vitamin D3. For the last synthesis of la-hydroxy-7-dehydrocholesterol recorded here, cholesta-l,4,6-triene-3-one was again used as starting steroid.122 Deconjugation of this trienone with strong base followed by immediate reduction with calcium borohydride led to the unstable 3/3-hydroxycholesta-l,5,7-triene which, without isolation, was converted into the 1,4-addition product (265) upon reaction with 4-phenyl-l,2,4-triazoline-3,5-dione. 

Of the numerous other aziridine syntheses, there are several multistep procedures from alkenes. Though not strictly within the scope of this review, the practising chemist will wish to consider their merits alongside the rect syntheses, and the main possibilities are summarized in Scheme 8. There are several good recent reviews, - and two older compilations remain very useful. - Syntheses of those intermediates of Scheme 8 accessible from alkenes are described in later sections of tiie present review, and syntheses of epoxides (Volume 6, Chapter 1.1 and Volume 7, Chapters 3.1 and 3.2) and triazolines (Volume 5, Ch ter 3.1) are described elsewhere in Comprehensive Organic Synthesis . It is important to note that by careful choice of route one can either commence with alkene (14) and retain the cisitrans stereochemistry in the resulting aziridine (16), or start with alkene (13) and change the cisitrans relatitm-ships of the substituents. 

Another synthesis of side-chain-hydroxylated cholesta-5,7-dien-3/S-ol derivatives uses the aldehyde (386), prepared by ozonolysis of the adduct of ergosteryl acetate with 4-phenyl-l,2,4-triazoline-3,5-dione. An aldol condensation between the aldehyde (386) and the pre-formed enolate of 3-methyl-3-tetrahydro-pyranyloxybutan-2-one (387) led to the enone (388), after acidic work-up. Reduc-... 

Methylhydrazino-1,4-benzodiazepine 17 reacts with acetaldehyde to yield the dihydrotriazolobenzodiazepine 18, along with a hydrazide, 19, suspected to be a secondary product from air oxidation of 18. The 1-methyl isomer (16), however, gives a Schiff base (20), similar to the one obtained in the Busch reaction (10MI1) for triazoline synthesis (Scheme 3) (79JOC2688). 

Triazolin-3-ones can be formed fromprimary amines in reaction withmethyl(ii)-iV-(ethoxymethylene) hydrazinecarboxylate, ° and the synthesis of the much-used 4-phenyl-l,2,4-triazoline-3,5-dione also starts from methyl carbazate, a final oxidation of 4-phenylurazole giving the carmine red crystalline product. ... 

The primary adducts, cyclohexadiene derivatives, formed by [4+2] cycloaddition of thiophene dioxides with dienophiles, may further undergo [4+2] cycloaddition with the dienophiles. Thus, the adducts 84 of 3,4-di-ferf-butylthiophene dioxide 83 with maleic anhydride and AT-phenylmaleimide further react with these dienophiles to give excellent yields of bis-adducts, which are composed of the endo-endo and endo-exo isomers, 85a and 85b (Scheme 49) [160]. A similar reaction was also observed with 3,4-dichlorothiophene 1,1-dioxide with N-butyl- and A-p-nitrophenylmaleimides (Scheme 50) [133]. The reaction of highly congested thiophene dioxides 87 with 4-phenyl-1,2,4-triazoline-3,5-dione provides a unique pyridazine synthesis since the bis-adducts 88 are converted into the corresponding pyridazines 89 in one pot and in good yields by treatment with KOH in methanol (Scheme 51) [174]. 

The synthesis of polyfunctional l,2,3-triazolin-5-ones was investigated somewhat earlier than the alkyl and aryl derivatives discussed in Chapter 13. For example, Curtius and his students prepared a variety of such compounds from sulfonylazides and malonic esters but failed to present evidence of the yields obtained (Eq. 1). ... 

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... 

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