Phenacylation of 1,2,4-triazole

Effects Depending on Reaction Mechanisms 147 Tab. 4.S. Results from the phenacylation of 1,2,4-triazole. 

I 4 Nonthermal Effects of Microwaves in Organic Synthesis Tab. 4.32. Phenacylations of 1,2,4-triazole. 

Cyclization of phenacyl halogenides with Schiff bases obtained from aminothiones of 1,2,4-triazole [87JCS(P 1) 1853 ] and thiazoles (88S729) proceeds by a somewhat different course [Eq. (98)]. 

Heating to reflux a pyridine solution of 3-substituted-5-(l-aroyl-l-bromo)methylthio-4-phenylamino-4//-[l,2,4]tria-zoles 81 (available from the corresponding 1,2,4-triazoles with phenacyl bromides and subsequent ultraviolet (UV) light-induced bromination) affords 3-substituted-6-aroyl-5,6-dihydro-5-phenyl[l,2,4]triazolo[3,4-6][l,3,4]thiadiazoles 82 (Equation 19) <1993IJH135>. 

Derivatives of the type (192) have been obtained from the appropriately fused 3-amino-1,2,4-triazole and phenacyl bromide (80KGS1695). 

Amino-l-nitro-l,2,4-triazole (581), obtained by nitration of 5-amino-triazole with acetyl nitrate, rearranges, on heating, to the nitramino-triazole (582). ° The combined action of sodium hydroxide, potassium iodide, tri-ethylamine, and sodium dihydrogen phosphite on the chloro-nitro-triazole (583) results in a mixture of the rearranged triazole (584), 3-chloro-l,2,4-triazole, and the coupled product (585). The stable betaine (586) has been prepared by treatment of 4-phenyl-1,2,4-triazole with phenacyl bromide, followed by tri-ethylamine. The meso-ionic triazolium thiolate (537 X = S) reacts with chlorine to form the dichloride (587 X = SCU), which has been converted into the betaine (588) by the action of diethyl bromomalonate in the presence of triethylamine. ... 

Several reports have dealt with fused [6+5] derivatives containing sulfur atoms. Thus, the synthesis and evaluation of the antibacterial and antifungal activity of i-triazolo [3,4 b][ 13,4]thiadiazoles, s-triazolo[3,4-b][ 1,3,4 thiadiazincs and s-triazolo[3, 4 /23][ 13,4]-thiadiazino-[5,6-b]quinoxaline have been reported <01IJC(B)368>. A series of 3,6-substituted-7//-5-triazolo[3,4-6][l,3,4]thiadiazines has been prepared through condensation of suitable 3-substituted-4-amino-5-mercapto-1,2,4-triazoles with phenacyl bromides and... 

The reaction of 3-aryl-5-sulfonyl-4//[l,2,4]triazole with phenacyl bromides in methanol gives 3,5-diarylthiazolo[2,3-c][l,2,4]triazoles (46) in one step (see Section 8.05.9.1.11) (Equation (114)) <88CAT91>. 

Direct alkylation with classical heating gave a mixture of 1- and 4-alkylated triazoles together with quaternary salts resulting from alkylations at both the 1 and 4 positions. Interestingly, it has been shown that benzylation and phenacylation occurred selectively at position 1 without any base under the action of irradiation and under solvent-free conditions (Scheme 10.94) [183]. The reaction with (2,4-dichloro)phenacyl chloride was studied in particular depth (Chapter 4). This reaction has been scaled-up to more than 100 g by use of a Synthewave 1000 oven. 

By reacting 3-thiol-5-phenyl-4-pyrrolyl-1,3,4-triazole (160) with chloroacetic acid or phenacyl bromide, the 3-carboxymethylthio- (161) and 3-phenacylthiotriazole (162) were obtained, and underwent intramolecular cyclization reactions via electrophilic substitutions. The cyclization of the former in boiling ppa produced thiadiazepinone (163) (38% yield), while the latter was cyclized to the phenyl derivative (164) (50% yield), 3,9-diphenyl-l,2,4-triazolo[3,4-t]pyrazolo[l,2-d]-l,3,4-thiadiazepine, by heating with phosphorus oxychloride (Scheme 28) <82G345>. 

Aqueous PEG 400 was also used in the formation of 1-aroylmethyl-l,2,3-triazoles 82 from phenacyl bromides, sodium azide, and terminal alk5mes under the copper(II) sulfate/sodium ascorbate catalysis [75]. Similar conditions (room temperature, 30 min) were applied to the syndesis of a variety of 1-substituted 4-aryl-l,2,3-triazoles with yield of 75-90% using the copper(II) sulfate/sodium ascorbate catal5dic system in aqueous PEG 400 [76]. a-Tosyloxy ketones 83, including cyclic, were also successfully adopted as substrates for this reaction (Scheme 49) [77,78]. It was demonstrated that copper(I) iodide could be replaced by the copper(II) sulfate/sodium ascorbate system. Some of the products 84 were reported [78] to inhibit Src kinase, a valid target for the therapy of cancer, acute ischemic stroke, and other diseases. 

The partial inhibition of the hydrolysis observed at pH < 4, and the negative salt effect, may be attributed to a specific cation-anion interaction. The proposed mechanism receives further support from the observed effects on the hydrolysis rates of increased viscosity of the medium and of added inorganic nucleophiles. Hydrazine or alkylhydrazines cleave and recyclize 1,3,4-thiadiazolium salts (114) to 1,2- or l,4-dihydro-l,2,4,5-tetrazines (115) in high yield. The action of arylhydrazine results in the alternative recyclization of the probable intermediate ArNHN=CR2NR N=CR SH, to 4-amino-1,2,4-triazolium salts (116). 5-Amino-2-imino-3-phenacyl-l,3,4-thiadiazolines (117) isomerize in boiling ethanol to 5-amino-3-mercapto-l-phenacyl-l,2,4-triazoles (118). This example... 

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