1.2.3- Triazole, oxidation

If the hydrazone is unsubstituted, dehydration with acetic anhydride gives a 2-acetyltriazole, which is readily converted into an unsubstituted triazole.Oxidation of a-diketone hydrazone oximes with cupric sulfate in aqueous pyridine leads to the formation of 2.ff-triazole-1-oxides. ... 

The oxide group mildly activates 3-substituted 1,2,3-triazole 1-oxides to electrophilic attack. Thus, 3-benzyl-1,2,3-triazole 1-oxide reacted much more rapidly than the unoxidized compound in giving the 5-bromo derivative, and there have been a number of other examples of 5-bromination and 5-chlorination of triazole oxides, including that of the 3-phenyl-l-oxide, which was not para-halogenated [87ACS(B)724]. 

Three methods for making 4,5,6,7-tetrahydrotriazoIopyridines use two fragments to form the triazole ring. The lithium derivative of A/-nitro-sopiperidine reacts with benzonitrile to give the 3-phenyl derivative 19.28 Diazonium salts react with a-amino acids to give mesoionic triazole oxides if pipecolic acid is used, the product is a tetrahydrotriazolopyridine 3-oxide... 

In peptide syntheses, where partial racemization of the chiral a-carbon centers is a serious problem, the application of 1-hydroxy-1 H-benzotriazole ( HBT") and DCC has been very successful in increasing yields and decreasing racemization (W. Kdnig, 1970 G.C. Windridge, 1971 H.R. Bosshard, 1973), l-(Acyloxy)-lif-benzotriazoles or l-acyl-17f-benzo-triazole 3-oxides are formed as reactive intermediates. If carboxylic or phosphoric esters are to be formed from the acids and alcohols using DCC, 4-(pyrrolidin-l -yl)pyridine ( PPY A. Hassner, 1978 K.M. Patel, 1979) and HBT are efficient catalysts even with tert-alkyl, choles-teryl, aryl, and other unreactive alcohols as well as with highly bulky or labile acids. 

Stilben-4-yl)naphthotriazoles (2) are prepared by diazotization of 4-amino-stilbene-2-sulfonic acid or 4-amino-2-cyano-4 -chlorostilbene, coupling with an ortho-coupling naphthylamine derivative, and finally, oxidation to the triazole. 

Most of the GA-synthesis inhibitors characterized so far affect two segments of the compHcated pathway from MVA to the many different GAs identified. The cycHzation reactions that produce / Akaurene are inhibited by the onium growth retardants, and the oxidations of /-kaurene to /-kaurenoic acid are sensitive to heterocycHc triazoles such as paclobutrazol and similar compounds. Other enzymes in the pathway are points for pathway dismption by as yet undeveloped GA biosynthesis inhibitors (236). 

When the operating temperature exceeds ca 93°C, the catalytic effects of metals become an important factor in promoting oil oxidation. Inhibitors that reduce this catalytic effect usually react with the surfaces of the metals to form protective coatings (see Metal surface treatments). Typical metal deactivators are the zinc dithiophosphates which also decompose hydroperoxides at temperatures above 93°C. Other metal deactivators include triazole and thiodiazole derivatives. Some copper salts intentionally put into lubricants counteract or reduce the catalytic effect of metals. 

Copper Corrosion Inhibitors. The most effective corrosion inhibitors for copper and its alloys are the aromatic triazoles, such as benzotriazole (BZT) and tolyltriazole (TTA). These compounds bond direcdy with cuprous oxide (CU2O) at the metal surface, forming a "chemisorbed" film. The plane of the triazole Hes parallel to the metal surface, thus each molecule covers a relatively large surface area. The exact mechanism of inhibition is unknown. Various studies indicate anodic inhibition, cathodic inhibition, or a combination of the two. Other studies indicate the formation of an insulating layer between the water surface and the metal surface. A recent study supports the idea of an electronic stabilization mechanism. The protective cuprous oxide layer is prevented from oxidizing to the nonprotective cupric oxide. This is an anodic mechanism. However, the triazole film exhibits some cathodic properties as well. 

Enamines and enolate anions react with benzofuroxan to give quinoxaline di-A -oxides (Scheme 38) (69AHC(10)1). Sydnones (274) with phenyl isocyanate give 1,2,4-triazoles (275) (76AHC(19)l), and from (276) the intermediate adduct (277) can be isolated (73JA8452). This is one of the few instances in which such primary cycloadducts have been isolated in the oxazole series of mesoionic compounds. 

Oxidative procedures have been utilized for the synthesis of both monocyclic five-membered heterocycles and their ring-fused analogs, although the ease of synthesis of the precursors for the latter ring closures results in wider application of this procedure. A variety of oxidizing agents have been used and the conversion of the benzylidene hydrazidines (221) into the 4-arylamino-l,2,4-triazole (222) was effected with mercury(II) oxide (77BCJ953). 

Oxidation of the hydrazone of 2-hydrazinopyrazole (226) with Pb(OAc)4 in CH2CI2 is a two-step reaction. The azine (227) was formed as an intermediate and this underwent ring closure to the 3H-pyrazolo[5,l-c][l,2,4]triazole (228) (79TL1567). A similar reaction applied to the benzal derivative of 2-hydrazinobenzothiazole (229) gave 3-phenyl-[l,2,4]triazolo[3,4-6]benzothiazole (230) together with a by-product (231) (72JCS(P1)1519). 

The use of an acidic solution of p-anisaldehyde in ethanol to detect aldehyde functionalities on polystyrene polymer supports has been reported (beads are treated with a freshly made solution of p-anisaldehyde (2.55 mL), ethanol (88 mL), sulfuric acid (9 mL), acetic acid (1 mL) and heated at 110°C for 4 min). The colour of the beads depends on the percentage of CHO content such that at 0% of CHO groups, the beads are colourless, -50% CHO content, the beads appear red and at 98% CHO the beads appear burgundy [Vdzquez and Albericio Tetrahedron Lett 42 6691 200]]. A different approach utilises 4-amino-3-hydrazino-5-mercapto-1,2,4-triazole (Purpald) as the visualizing agent for CHO groups. Resins containing aldehyde functionalities turn dark brown to purple after a 5 min reaction followed by a 10 minute air oxidation [Coumoyer et al. J Comb Chem 4 120 2002]. 

Bis(3,4-diethyl-2-pyrrolylmethyl)-3,4-dietliyl-l//-pyrrole (2), prepared in situ from the di-t-butylester of the 5,5 -dicarboxylic acid (/), reacts with 4//-1,2,4-triazole-3,5-dialdehyde (3) in di-chloromethane in the presence of trifluoroacetic acid and 2,3-dichloro-5,6-dicyano-/)-benzoquino-ne as an oxidation reagent. Dark blue crystals are obtained after chromatographic purification. The dark violet chloroform solution fluoresces purple at 360 nm and gives the NMR experiments 39. Which compound and which tautomer of it has been formed ... 

A mixture of 300 ml. of water, 150 ml. of concentrated nitric acid, and 0.2 g. of sodium nitrite (Note 2) is placed in a 2-1. threenecked flask equipped with a stirrer and a thermometer. The stirred mixture is warmed to 45°, and 2 g. of l,2,4-triazole-3(5)-thiol is added. When oxidation starts, as indicated by the evolution of brown fumes of nitrogen dioxide and a rise in temperature, a bath of cold water is placed under the reaction flask to provide cooling and an additional 99 g. (total, 101 g. 1 mole) of 1,2,4-triazole-3(5)-thiol is added in small portions over the course of 30-60 minutes. The rate of addition and the extent of cooling by the water bath are so regulated as to keep the temperature close to 45 7° all during the addition. The water bath is kept cold by the occasional addition of ice. 

Triazole has been prepared by the oxidation of substituted 1,2,4-triazoles, by the treatment of urazole with phosphorus pentasulfide, by heating equimolar quantities of formyl-hydrazine and formamide, by removal of the amino function of 4-amino-l,2,4-triazole, by oxidation of l,2,4-triazole-3(5)-thiol with hydrogen peroxide, by decarboxylation of 1,2,4-triazole-3(5)-carboxylic acid, by heating hydrazine salts with form-amide,by rapidly distilling hydrazine hydrate mixed with two molar equivalents of formamide, i by heating N,N -diformyl-hydrazine with excess ammonia in an autoclave at 200° for 24 hours, and by the reaction of 1,3,5-triazine and hydrazine monohydrochloride. ... 

A combination of the preceding type of synthesis and of cyclization of 4-amino-5-arylazopyrimidine can be seen in the novel procedure of Richter and Taylor. Proceeding from phenylazomalonamide-amidine hydrochloride (180), they actually close both rings in this synthesis. The pyrimidine ring (183) is closed by formamide, the triazole (181) one by oxidative cyclization in the presence of cupric sulfate. Both possible sequences of cyclization were used. The synthetic possibilities of this procedure follow from the combination of the two parts. The synthesis was used for 7-substituted 2-phenyl-l,2,3-triazolo[4,5-d]-pyrimidines (184, 185). An analogous procedure was employed to prepare the 7-amino derivatives (188) from phenylazomalondiamidine (186). 

The classical age of preparative organic chemistry saw the exploration of the extensive field of five-membered heterocyclic aromatic systems. The stability of these systems, in contrast to saturated systems, is not necessarily affected by the accumulation of neighboring heteroatoms. In the series pyrrole, pyrazole, triazole, and tetrazole an increasing stability is observed in the presence of electrophiles and oxidants, and a natural next step was to attempt the synthesis of pentazole (1). However, pentazole has eluded the manifold and continual efforts to synthesize and isolate it. 

Mendoza and Torres and later Torres alone carried out systematic studies of the consequences of replacing an isoindole ring by a 1,2,4-triazole one. A first attempt to introduce two triazole subunits gave the dihydro 20-77 ring 86 instead of the I8-77 system 87 [89JCS(P2)797]. All attempts to oxidize 86 into 87 failed. Compound 87 was calculated to be less stable than... 

Another example of this rearrangement has been used to prepare 1,2,3-triazole 146 from furazanic phenylhydrazone 147 (Scheme 84) [93JCS(P1)2491]. Interestingly, furoxanic Z-phenylhydrazones 150 underwent thermal recyclization to 1,2,3-triazole A-oxides 152, evidently through intermediate 151. Treatment of the hydrazone 150 with rerr-BuOK leads to the nitromethyl derivative 149 [OOOMIl] (Scheme 84). Lead tetraacetate oxidation of 147 with subsequent Lewis acid treatment of the initially formed intermediate afforded indazole 148 (Scheme 84) (85JHC29). 

Other examples of nucleophilic attack on a furoxan ring leading to ring opening/recyclization are the formation of 1,2,3-triazole 1-oxides 198 from 4-alkylamino-3-nitrofuroxans 197 and alkylamines (Scheme 129). 3-Amino-4-nitrofurazan was observed as by-product (95MC194, 96CHE580, 96KGS675). 

Alkylaminofurazans of type 202 were nitrosated to give the corresponding ni-trosoamino derivatives, which were cyclized to fused 1,2,3-triazole 2-oxides 203 in 70-92% yields (96TL8577) (Scheme 133). 

UV irradiation of 3-aminopyrido[4,3-e]-1,2,4-triazine 1-oxides 7 or 1,2,4-triazine 4-oxides 8 leads to deoxygenation, i.e., loss of the 7V-oxide function resulting in the corresponding 3-aminopyrido[4,3-e]-1,2,4-triazines 9 and 1,2,4-triazines 10 (76ACH327, 76LA153). At the same time, UV irradiation of the 1,2,4-triazine 4-oxides unsubstituted at the 5 position proceeds as a ring contraction to form triazoles 11 (76LA153). 

Free carbenes based on 1,2,4-triazole are not as numerous as those based on imidazole (70ZN(B)1421, 95AGE1021, 97JA6668, 98JA9100). The carbene complex 169 (Ar = Ph, p-Tol) is prepared by the [3 + 2] cycloaddition route from [W(CO)j(C+=NC-HCOOEt)]- and aryldiazonium (930M3241). Oxidative decomplexation causes tautomerization of the 1,2,4-triazole ligand, the products being 170 (Ar= Ph, i-Tol). 

Lithium 1,2,4-triazolate with [Rh2( j,-Ph2PCH2PPh2)(CO)2( j.-Cl)]PFj. gives the A-framed complex 177 (L=L = CO) (86IC4597). With one equivalent of terf-butyl isocyanide, substitution of one carbon monoxide ligand takes place to yield 177 (L = CO, L = r-BuNC), whereas two equivalents of rerr-butyl isocyanide lead to the product of complete substitution, 177 (L = L = r-BuNC). The starting complex (L = L = CO) oxidatively adds molecular iodine to give the rhodium(II)-rhodium(II) cationic species 178. 

MP2/6-31-l-G calculations in the gas phase indicate that 2//-1,2,3-triazole is about -5 kcal/mol more stable than the H isomer [92JOC3698]. The energy differences between 1-hydroxy-l,2,3-triazole 56a and its 2H (56b) and 3// (56c) tautomers were investigated up to the MP4(SDTQ)/6-31 - -G level. The 1 -hydroxy form 56a is the preferred tautomer in the gas phase, but owing to the strong polarity of the V-oxide 3// tautomer 56c, this is the most stable structure in solution (Scheme 37) [92JOC3698]. 

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