One triazoles

Acyl derivatives of azoles containing two different environments of nitrogen atoms can rearrange. For example, 1-acyl-1,2,3-triazoles are readily isomerized to the 2H-isomers in the presence of triethylamine or other bases the reaction is intermolecular and probably involves nucleophilic attack by N-2 of one triazole on the carbonyl group attached to another (74AHC(16)33). 

More recently, activity in the held of the preparation of phthalocyanine-like compounds useful in material science concentrated on compounds containing only one triazole subunit (triazolophthalocyanines) 89 [94JCS(CC)1525 95ICA(230)153].These aromatic compounds (without or with metals in the cavity) present a problem of annular tautomerism of triazoles, but as yet it is known only that the NH is outside the cavity. 

On the basis of the same principle, we developed a three-component synthesis of macrocycles starting from azido amide (46), aldehyde (47) and a-isocyanoaceta-mide (48) (the cx-isocyanoacetamides are easily available, see [84—86]) bearing a terminal triple bond (Scheme 11) [87]. The sequence is initiated by a nucleophilic addition of isonitrile carbon to the in situ generated imine 50 led to the nitrilium intermediate 51, which was in turn trapped by the amide oxygen to afford oxazole 52 (selected examples [88-94]). The oxazole 52, although isolable, was in situ converted to macrocycle 51 by an intramolecular [3+2] cycloaddition upon addition of Cul and diisopropylethylamine (DIPEA). In this MCR, the azido and alkyne functions were not directly involved in the three-component construction of oxazole, but reacted intramolecularly leading to macrocycle once the oxazole (52) was built up. The reaction created five chemical bonds with concurrent formation of one macrocycle, one oxazole and one triazole (Scheme 15). 

In addition, bifunctionalized carbohydrate derivatives containing simultaneously one azido and alkyne groups have been intermoleculary reacted, affording cyclic carbohydrate-containing molecule of interest that also possess more that one triazole ring in their structures. 

The progress of the reaction was again monitored by NMR spectroscopy. Our criterion for catalytic turnover was that each cucurbituril molecule would lead to the formation of more than one triazole ring. This ratio was calculated from the integration of the sum of all triazole proton resonances (encapsulated and free) divided by 1/12 of the integration arising from a cucurbituril resonance. In an exploratory effort the effect of catalyst concentration, temperature and type of solvent, as shown in Table 1.2, were investigated. ... 

Poly(triazoles) and poly(oxadiazoles), each with two hetero rings per repeat unit, are obtained by the process described in the previous section. Poly(triazoles) with one triazole residue per structural element are produced from terephthalic acid and hydrazine with subsequent cyclocondensation of... 

As an example, chloride has been shown fo be an effective template for the preparation of macrocycles incorporating heterocycles, and where the templating anion is generated in the course of the reaction. In the case of the macrocycle incorporating two imidazolium moieties and one triazole residue (Scheme 2), the yield of the product was shown to depend critically on the precursors used for the reaction. When a bis-imidazole incorporating triazole as a spacer was used with mefa-dichloroxylylene, the yield of the reaction was never >20% even in the presence of additional chloride ions. On the other hand, when a bis-imidazole with a mefa-xylylene spacer was used with bis-chloromethyl-triazole, the yield was 50%. In the presence... 

Besides being useful precursors to pyrroles pyridine-2-ones -4-ones, -4-thiones. and -4-imines 4-alkylidene-dihydropyridines thiophenes 1,2,4-triazoles thiapyrane-2-thiones, isoquinoline-3-ones isoben-zothiophenes and 4-mercaptoimidazolium hydroxide inner salts, mesoionic thiazoles are potentially useful in the construction of molecules with herbicidic (39). central nerve stimulating, and antiinflammatory properties (40,41). Application in dye synthesis has likewise been reported (42). 

Nitrogen nucleophiles used to diplace the 3 -acetoxy group include substituted pyridines, quinolines, pyrimidines, triazoles, pyrazoles, azide, and even aniline and methylaniline if the pH is controlled at 7.5. Sulfur nucleophiles include aLkylthiols, thiosulfate, thio and dithio acids, carbamates and carbonates, thioureas, thioamides, and most importandy, from a biological viewpoint, heterocycHc thiols. The yields of the displacement reactions vary widely. Two general approaches for improving 3 -acetoxy displacement have been reported. One approach involves initial, or in situ conversion of the acetoxy moiety to a more facile leaving group. The other approach utilizes Lewis or Brmnsted acid activation (87). 

Annular tautomerism (e.g. 133 134) involves the movement of a proton between two annular nitrogen atoms. For unsubstituted imidazole (133 R = H) and pyrazole (135 R = H) the two tautomers are identical, but this does not apply to substituted derivatives. For triazoles and tetrazoles, even the unsubstituted parent compounds show two distinct tautomers. Flowever, interconversion occurs readily and such tautomers cannot be separated. Sometimes one tautomeric form predominates. Thus the mesomerism of the benzene ring is greater in (136) than in (137), and UV spectral comparisons show that benzotriazole exists predominantly as (136). 

Mesoionic compounds of the type designated (76AHC(19)l) as A are capable of isomerism. In one case in the 1,2,4-triazole series, isomerism of the pair (64) (65) has been demonstrated (67TL4261). 

In azole chemistry the total effect of the several heteroatoms in one ring approximates the superposition of their separate effects. It is found that pyrazole, imidazole and isoxazole undergo nitration and sulfonation about as readily as nitrobenzene thiazole and isothiazole react less readily ica. equal to m-dinitrobenzene), and oxadiazoles, thiadiazoles, triazoles, etc. with great difficulty. In each case, halogenation is easier than the corresponding nitration or sulfonation. Strong electron-donor substituents help the reaction. 

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. 

Phenylisoxazolin-5-one condensed with anthranal to give a tricyclic isoxazolylquinoline (Scheme 72) <78CZ264). 3-Methyl-4-phenylazoisoxazoline-5-thione reacted with ethyl chloroacetate for form an intermediate isoxazolethiol, which on heating generated a 1,2,3-triazole (Scheme 73). 

H- Pyrro lo[l,2-c][l,2,4]triazol-3-ones synthesis, 6, 991 Pyrroloyl azides Curtius rearrangement, 4, 288 Pyrrolyl anions acylation, 4, 232 alkylation, 4, 235 solvent effects, 4, 236 C-alkylation... 

C=N, C=S, C=C, and N N containing substrates. Thus oxa2oles, imidazoles, thiazoles, p rrroles, and 1,2,4-triazoles have been prepared, respectively. Furthermore, p-tolylsulfonylmethyl isocyanide has found use in a one-step conversion of ketones into cyan-idea and in a two-step synthesis of a-hydroxyaldehydes from ketones. ... 

Phenylmethyltriazole Carboxylic Acid. —The mother substance of this compound is a triazole, viz., pyrro-n/ d-diazolc, which is one of four isomeric compounds ... 

Triazole 15 was mixed with polyphosphorie aeid (150 mL) and the mixture was heated until gas evolution eeased (130-180"C) (Caution It is important to note that one mole of is evolved). After eooling, the syrup was poured into iee water (2 L), and the precipitate was eolleeted, washed with H2O, heated on a steam bath with 25% ammonia (100 mL), and filtered. The produet was then washed with H2O and erystallized from pyridine to furnish 16 in 30% yield. 

For the preparation of triazolopyrimidines three main types of synthesis are in use. The first of these proceeds from a pyrimidine derivative (especially the 4,5-diamino derivatives) and closes the triazole ring. The second method proceeds, on the contrary, from derivatives of u-triazole to close the pyrimidine ring. The third method finally is one which yields the derivatives through substitution or replacement of substituents in compounds prepared by one of the first-named procedures. 

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). 

Contributions in this section are important because they provide structural information (geometries, dipole moments, and rotational constants) of individual tautomers in the gas phase. The molecular structure and tautomer equilibrium of 1,2,3-triazole (20) has been determined by MW spectroscopy [88ACSA(A)500].This case is paradigmatic since it illustrates one of the limitations of this technique the sensitivity depends on the dipole moment and compounds without a permanent dipole are invisible for MW. In the case of 1,2,3-triazole, the dipole moments are 4.38 and 0.218 D for 20b and 20a, respectively. Hence the signals for 20a are very weak. Nevertheless, the relative abundance of the tautomers, estimated from intensity measurements, is 20b/20a 1 1000 at room temperature. The structural refinement of 20a was carried out based upon the electron diffraction data (Section V,D,4). 

In NMR speetra of trialkyltin derivatives of 1,2,3-triazoles, C(4) and C(5) atoms show one eommon signal at the lowest attained temperature of solution, -50°C [77JOM(132)69]. This observation was explained by the symmetrie strueture 42c of the eompounds (R = COOMe) [77JOM(127)273]. However, rapid annular tautomerism explains this observation equally well and eannot be ruled out. 

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