Lithium 1,2,4-triazolate. reaction with

One representative synthesis of prothioconazole starts [95] with the addition of the Grignard derivative of 2-chlorobenzyl chloride on the carbonyl double bond of chloromethyl 1-chloro-cyclopropyl ketone (Scheme 17.19). The untouched chlorine atom of the chloromethyl group is then classically substituted with 1,2,4-triazole. From this intermediate, one way to obtain the 2,4-dihydro-3H-l,2,4-triazole-3-thione of prothioconazole is by direct lithiation of the 1,2,4-triazole at position 5 with n-butyl lithium and reaction with sulfur. The commercially available compound is a mixture of two enantiomers (chirality of the quaternary carbon bearing the hydroxy group). 

The direct lithiation of a 2-substituted 1,2,3-triazole has not been reported. Halogen-metal exchange of 4,5-dibromotriazole with n-butyllithium at — 80 °C occurs smoothly and the subsequent reaction of the lithium intermediate (244) with various electrophiles except aldehydes gives the 4-bromo-5-substituted triazoles (245) (Scheme 46). The corresponding 1-substituted 4,5-dibromo-1,2,3-triazole undergoes a similar reaction at the 5-position . 

As the number of nitrogen heteroatoms increases, the stability of lithium azoles decreases the 5-lithio derivatives of 1,2,3-triazoles 778 ring-open spontaneously. l-Methyltetrazol-5-yllithium decomposes to nitrogen and lithium methyl-cyanamide above 50 G, although it gives the expected Grignard-like reactions with bromocyanogen, esters, ketones, and sulfur at lower temperatures. 

Middleton established that reaction of 1,2-dialkylhydrazines with sulfur and reduction of sulfinylhydrazines (R2N—N=S=0) with lithium aluminium hydride yielded highly colored N-thionitrosoamines (95), which are stable at < ca. -30°C (66JA3842). However, it was deduced from spectroscopic data that these were not true RN=S species a high contribution from the dipolar resonance form accounts for their stability. Nonetheless, compound 95 will act as a 277 component in an inverse electron demand Diels-Alder reaction with a tetrazine derivative to yield triazole 96 (79CZ230). 

A dipolar intermediate is also generated from trimethylsilyl diazomethane and n-butyl lithium, which on reaction with alkyl or aryl isocyanates gives rise to the formation of 1-substituted 5-hydroxy-1,2,3-triazoles 449". ... 

Trimethylsilyldiazomethane reacts with n-butyl lithium to give Me3SiC(Li)N2, which undergoes a [3+2] cycloaddition reaction with ketenimines to give the 1,2,3-triazoles 93 in 67-82 % yields... 

Diazo(trimethylsilyl)methyl lithium (3) was found to be the reagent of choice for the synthesis of azoles from heterocumulenes (Scheme 8.43). The reaction is typically carried out in ether at 0-20 °C. Thus, alkyl- (or aryl-)substituted keteni-mines are transformed into 1,2,3-triazoles 188 (246), while C-acceptor-substituted ketenimines yield either 4-aminopyrazoles 189 or 1,2,3-triazoles, depending on the substituents (247). Isocyanates are converted into 5-hydroxy-1,2,3-triazoles 190 (248). Reaction of 3 with isothiocyanates are strongly solvent dependent. 

Diazo compounds generally do not undergo [3 + 2] cycloaddition with unactivated nitriles under purely thermal, noncatalyzed conditions. The formation of 4-R-5-trimethylsilyl-l//-l,2,3-triazoles from the reaction of diazo(trimethylsilyl)-methyl lithium and a broad range of nitriles [RCN R = alkyl, aryl, SEt, OPh, PO(OEt)2] appears to be an exception, but this reaction most likely occurs in a stepwise manner with initial nucleophilic attack at the nitrile (275). 

Reduction of triazolinones with phosphorus sulhde has been one of the early routes to triazoles (o5JCS625). Milder reactions may differentiate between conjugation of the ring double bond with C=0 (139) or the lack of it (140) as in Scheme 48 (71bsf3296). The formation of triazole in the reduction of the triazolinone (140) with lithium aluminum hydride (7ibsf3296) is explicable through the formation of a hydroxytriazoline intermediate. 

It is possible to construct tertiary alcohols in a one-step process from an a-1,2,4-triazol-1-yl ketone with a suitable carbanion (Figure 22). In this case the ester enolate generated using lithium diisopropylamide gives a much better yield than the product of the Reformatsky reaction. 

The reactions between 4-amino-1,2,4-triazoles and 2-polyfluoroacylcycloalkanone lithium salt form polycyclic nitrogen-containing heterocycles with polyfluoroalkyl substituents (99IZV562) (Scheme 111). 

Under our best conditions, tra s-A,A/ -dimethylcyclohexyl-1,2-diamine, Cul, and KOH in aqueous acetonitrile produced up to 87% solution yield of the desired isomer (2), with a 20 1 0.5 ratio of regioisomers with respect to the triazole. The potassium salt was not crystalline, and as such, had excellent solubility in the reaction medium (ca. >40mg/mL). In contrast, the lithium salt and the freebase form of azaindole 2 had <2 mg/mL solubility. Thus, to isolate the lithium salt, after extraction of the reaction mixture with aqueous KOH, we performed a salt metathesis from potassium to lithium by the simple addition of lithium bromide. This resulted in the direct crystallization of the product in excellent yield and quality. Under these conditions, the lithium salt was isolated as a potassium bromide co-crystal. This co-crystal form demonstrated greatly enhanced filtration rates versus the free-base form of 2, due to its improved crystal morphology (Scheme 29). 

When chlorotrimethylsUane [(013)3810] is treated with lithium azide (UN3) in oxacyclopentane (THF), trimethylsilylazide [(CH3)3SiN3] results. Treatment of the latter with 2-butyne (dimethylacetylene, CH3C=CCH3) results in a cycloaddition reaction (Scheme 10.64), and, what is of particular interest, the 1-trimethylsilyl-l,23-triazole that results undergoes a 1,5-sigmatropic rearrangement to generate the more stable 2-trimethylsilyl-l, 2,5-triazole. 

Lithium dicyano- 1,2,3-triazolate was reported as a useful electrolyte (38) [45]. 1-Butyl-3-methylimidazoliiun 3,5-dinitro-l,2,4-triazolate (39) (Fig. 2) (m.p. 32 °C, rmaterial Some novel ionic liquids made up of azolium cations and anions were also reported. These salts are 1-ethyl-3-methyUmidazohum 1,2,4-triazolate (40) (Tg - 76 °C, T 207 °C, 7] 60.2 cP at 25 "C) and tetrazolate (41) (Tg -89°C, t] 42.5 cP at 25 °C) (Fig. 2). Both 40 and 41 were prepared by the coupUng reactions of 1-ethyl-3-methylimidazolium hydroxide with triazole or tetrazole, respectively [50]. 

Low yields of a mixture of cis- and trons-acetylenic thiirans (18) were obtained by treatment of lithium salts of 2-propargylthiothiazolines (17) with benzaldehyde. A mechanism was proposed. Thiiran was proposed as a product, although not identified, in the reaction of oxiran with 3-/3-hydroxyethylthio-1,2,4-triazoles (19) to yield N-/3-hydroxyethyltriazo-linones (20). ... 

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