1.2.3- Triazoles substituents

Dihydrazide 231 was also used in the synthesis of thienothiophenes containing triazole substituents. For example, the reaction with phenyl isothiocyanate in ethanol produces di(A -phenylthiocarbamoyl)carbohydrazide 238, whose treatment with KOH followed by acidification affords compound 239. Diazotization of dihydrazide 231 with 10% sodium nitrite in acetic acid gives diazide 240. The reactions of the latter with compounds containing the active methylene group, viz., ethyl cyanoacetate, malononitrile or diethyl malonate, in the presence of sodium ethoxide, yield the corresponding ditriazole derivatives 241-243. 

Many chemical compounds have been described in the Hterature as fluorescent, and since the 1950s intensive research has yielded many fluorescent compounds that provide a suitable whitening effect however, only a small number of these compounds have found practical uses. Collectively these materials are aromatic or heterocycHc compounds many of them contain condensed ring systems. An important feature of these compounds is the presence of an unintermpted chain of conjugated double bonds, the number of which is dependent on substituents as well as the planarity of the fluorescent part of the molecule. Almost all of these compounds ate derivatives of stilbene [588-59-0] or 4,4 -diaminostilbene biphenyl 5-membeted heterocycles such as triazoles, oxazoles, imidazoles, etc or 6-membeted heterocycles, eg, coumarins, naphthaUmide, t-triazine, etc. 

Substituents are expected to alter the electron density at the multiply-bonded nitrogen atom, and therefore the basicity, in a manner similar to that found in the pyridine series. The rather limited data available appear to bear out these assumptions. The additional ring nitrogen atoms in triazoles, oxadiazoles, etc. are quite strongly base-weakening this is as... 

Ring substituents can have a considerable effect on the acidity of the system. In the 1,2,4-triazole series a 3-amino group decreases the acidity to 11.1, a 3-methyl group to 10.7, whereas a 3-phenyl group Increases the acidity to 9.6, and 3,5-dlchloro substitution to 5.2 (71PMH(3)1). 

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. 

Triazoles are brominated at the 4- or 5-positions, but only if there is no Af-substituent <74AHC(16)33). This also applies to 1,2,4-triazoles. Af-Halogeno derivatives are frequently isolated as intermediates (81HC(37)289). 

Discussion of these compounds is divided into isomers of aromatic compounds, and dihydro and tetrahydro derivatives. The isomers of aromatic azoles are a relatively little-studied class of compounds. Dihydro and tetrahydro derivatives with two heteroatoms are quite well-studied, but such compounds become more obscure and elusive as the number of heteroatoms increases. Thus dihydrotriazoles are rare dihydrotetrazoles and tetrahydro-triazoles and -tetrazoles are unknown unless they contain doubly bonded exocyclic substituents. 

In contrast, substituents in 1,2,4-triazoles are usually rather similar in reactivity to those in benzene although nucleophilic substitution of halogen is somewhat easier, forcing conditions are required. 

It is instructive to consider Af-substituted azoles in reverse, i.e. the azole ring as the substituent linked to some other group. Hammett and Taft cr-constant values for azoles as substituents are given in Table 11. The values show that all the azoles are rather weak net resonance donors, imidazole being the strongest. They are all rather strong inductive acceptors, with pyrazole considerably weaker in this respect than imidazole or the triazoles. 

The 1-azirines obtained from the vapor phase pyrolysis of 4,5-disubstituted 1-phthalimido-1,2,3-triazoles (157) have been found to undergo further thermal reactions (71CC1S18). Those azirines which contain a methyl group in the 2-position of the ring are cleaved to nitriles and phthalimidocarbenes, whereas those azirines which possess a phenyl substituent in the 2-position rearrange to indoles. 

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. 

Whereas most 3-amino-l,2,4-triazoles prefer the amino form 60 [76AHC (SI), p. 439,445 80KGS1414], strong electron withdrawing substituents can lead to the predominance of the imino form, as is the case of the compound 65 (R = C3F7) (80KGS1414) or to 5-amino tautomer 61 (R = H, R = CF3) [98AX(C)442]. This conclusion was based on gas-phase IR and mass-spectroscopic studies. 

Type 125 0x0 forms are characteristic for 5-hydroxy-l,2,4-triazoles [76AHC(S1), pp. 379, 388], These forms are additionally stabilized by an electron-withdrawing substituent, R = NO2 (98MRC343). Both hydroxy and 0x0 tautomers are capable of forming stable dimers owing to the in-termolecular hydrogen bonds (126 and 127 [76AHC(S1), pp. 377,379). 

Since HF calculations have a tendency to underestimate the N—N and the C—N bond lengths in triazoles [98JPC(A)620, 98JPC(A) 10348], the structural parameters should be computed at least at the DFT or MP2 levels. This is particularly true if electron-donating substituents are attached to the ring. Nitrogen NMR shielding tensors were computed for a set of methylated triazoles and tetrazoles but will be discussed in the context of tetrazoles (cf. Section IV,B). 

Benzotriazole can exist in two tautomeric forms, l-//-benzotriazole (6.46, R = H) and 2-/f-benzotriazole. If the aromatic ring contains a substituent, the 1- and 3-nitrogen atoms of the triazole are not equivalent, and therefore a 3-//-benzotri-azole derivative can also exist. The equilibrium between the 1 -H and 2-H tautomers of benzotriazoles is strongly on the side of the 1 -H tautomer, in contrast to triazole where the 2-H tautomer is dominant. Tomas et al. (1989) compared experimental data (enthalpies of solution, vaporization, sublimation, and solvation in water, methanol, and dimethylsulfoxide) with the results of ab initio theoretical calculations at the 6-31G level. 

Nevertheless, the placement of two Cl atoms on the C and C carbon atoms of the NHC skeleton, the presence of the strong SO Ar electron-withdrawing group on the aryl A-substituents, or the modification of the NHC skeleton from an imidazol-to a triazol-type, have allowed to fill the gap between the TEP of phosphines and NHCs, see Pig. 1.14. 

Results corresponding to those for the substituted N-benzoylimidazoles have been observed for a series of meta- and para-substituted /V-benzoyl-1,2,4-triazoles which, under the same conditions and over the whole range of substituents, show reaction rates about ten times faster than those of the imidazolides.[9],[10]... 

Ligands with S donors in addition to N and or O donors bound to Co11 are reasonably large in number. For example, the 4-amino-3-alkyl-l,2,4-triazole-5-thione can bind Co11 as a chelate employing the primary amine and thione substituents on the five-membered ring,510 whereas the trifluoromethyl ligand (afmt) forms [Co(afmt)2(H20)2](N03)2, defined as the A -irons isomer... 

Substituted (5R,6A,)-6-(dimethyl(phenyl)silyl)-2-phenyldihydropyrazolo[l,2- ][l,2,4]triazole-l,3(2//,5//)-dione 716, synthesized via the [3+2] annulation of a-substituted allylic silanes 715 with PTAD, were oxidized to the corresponding hydroxy substituted urazoles 717. This work shows that allylsilanes with a single substituent at the allylic carbon undergo exclusive stereoselective [3+2] annulation (Scheme 114) <2007TL6671>. 

A different result was obtained in the cycloaddition to methylenecyclo-propanes 216-218 tearing alkoxycarbonyl substituents on the cyclopropyl ring. In this instance, 1,2,3-triazoles 220 isomeric with the triazolines 219 were formed in the reaction [57]. The formation of triazoles 220 is rationalised by the intermediate formation of triazolines 219, which are unstable under the reaction conditions and undergo a rearrangement to the aromatic triazoles via a hydrogen transfer that probably occurs with the assistance of the proximal ester carbonyl (Scheme 35). The formation of triazoles 220 also confirms the regio-chemistry of the cycloaddition for the methylene unsubstituted methylene-cyclopropanes, still leaving some doubt for the substituted ones 156 and 157. 

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