1.2.3- Triazoles substitution

A-Substituted 4- or 5-fluoro-l,2,3-triazoles have been prepared by 1,3-cycloaddition reactions with azides. For example, reaction of perfluoropropadiene with phenylazide produces a mixture of regioisomeric 1,2,3-triazoles substituted with the phenyl, fluoro, and trifluoromethyl groups (Fig. 3.90). The major isomer was... 

S 1,2,3-Triazole-Substituted Oleanolic Acid Derivatives as Anticancer Agents... 

A related method was reported by Katritzky et al. [25], who prepared 1-alkoxy-l-(l,2,4-triazol-l-yl)allenes from the corresponding triazole-substituted alkynes, e.g. the reaction of 18 to 19 in Eq. 8.2. In this case the generated allenyl anion was trapped with methyl iodide. 

Protonation of triazole-substituted 1,2-allenyl ether 237 affords the ,/i-unsaturated... 

Other 7- substituents that have been introduced include the dialkylamino, acetamido, hydroxy, alkoxy and alkylthio groups (B-71MI11209). Acylation of the 7-amino group by heterocycles such as cyanuric chloride and its derivatives was inevitable, as was incorporation of a 7-triazole substitution pattern by diazotization of the 7-amino group and o-coupling with 2-naphthylamine followed by triazolization (94). 

Cosyn L, Palaniappan KK, Kim SK, Duong HT, Gao ZG, Jacobson KA, Van Calenbergh S (2006b) 2-Triazole-substituted adenosines a new class of selective A3 adenosine receptor agonists, partial agonists, and antagonists. J Med Chem 49(25) 7373-7383... 

Triazole-substituted adenosines a new class of selective A3 adenosine receptor agonists, partial agonists, and antagonists. J Med Chem 49 7373-7383... 

Quaternization takes place so as to maximize the distance between substituents on annular N. Thus a triazole substituted on N-1 is quaternized on N-4 and vice versa. However, quaternization of triazolinones and triazolinethiones or diquaternization of aromatic triazoles may involve N-1 and N-2. Structural proofs of quaternized compounds are simple in cases such as that of (63) ready removal of the acetyl group from N-1 leaves (65). If then (63) arose from the methylation of (66), the quaternized site is determined unambiguously. 

However, interchange reactions provided the most versatile approach to this class of compounds. Azole interchange was carried out on the dithiocarbamate-phosphorane 435a pyrazole, triazole, substituted imidazoles displaced in DMF solution the imidazolyl group, and the modified azolyl dithiocarbamates obtained in this way were cyclized to the corresponding 2-azolylpenems of formula 436a. 

Classification Triazole-substituted aromatic hydrocarbon heterocyclic Empirical CsHsN,... 

CAS 95-14-7 EINECS/ELINCS 202-394-1 Synonyms 1,2-Ami nozophenylene Azimidobenzene Azi mi nobenzene Benzene azimide Benzisotriazole Benzotriazole (INCI) 1,2,3-Benzotriazole Benztriazole BZT 2,3-Diazaindole Triazaindene 1,2,3-Triazaindene Classification Triazole-substituted aromatic hydrocarbon heterocyclic Empiricai CeHsNs... 

Synthesis and structure activity relationships of 2-triazole substituted analogs of 5 -0-[N-salicyl(sulfamoyl)]adenosine Potent antitubercular agents that target siderophore biosynthesis... 

Triazole-substituted piperazine amides mimicking )8-tum stractures were reported by the Burgess group. Fifteen piperazine amides were prepared and isolated in high yields (23, 71-96%, Scheme 10.7) and used in couplings with dichlorotriazine derivatives (tagged with fluorescein or an alkyne) to afford combinatorial libraries 24, which were... 

Saravanan C, Senthil S, Kannan P (2008) Click chemistry-assisted triazole-substituted azobenzene and fulgimide units in the pendant-based copoly(decyloxymethaciylate)s for dual-mode optical switches. J Polym Sci Part A Polym Chem 46 7843-7860 Sawamura M, Kawai K, Matsuo Y, Kanie K, Kato T, Nakamura E (2002) Stacking of conical molecules with a fullerene apex into polar columns in crystals and liquid crystals. Nature 419 702-705... 

The [4+2] cycloaddition reactions of some triazole substituted 3,5-dichloro-2(lH)-pyrazinones have been studied by Kaval et al. (2006). They developed the required intermediates from the corresponding 3,5-dichloropyrazinones, following either a nucleophilic substitution or a Sonogashira reaction to install the alkyne handle on the scaffold. The various triazole derivatives linked to the pyrazinones were synthesized through a microwave-assisted CuAAC reaction. Then [4+2] cycloaddition reactions were carried out under microwave irradiations with dimethyl acetylenedicaiboxylate (DMAD) at 180-200 °C for 10-20 min, and the corresponding highly decorated pyridine and pyridine scaffolds were isolated in good yields. 

Triazole-substituted titanocenes may be synthesized by a strain-driven 1,3-dipolar cycloadditions between azide-functionalized titanocenes and cyclooctyne. Titanocene derivative are interesting complexes since they are a promising class of cytotoxic compounds, efficient reagents and catalysts, and organometallic gelators. Azide-substituted cationic titanocenes reacted with cyclooctyne in CH2CI2 at room temperature to give the expected product with yields between 75% and 92% [84]. 

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). 

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). 

For both azole and benzazole rings the introduction of further heteroatoms into the ring affects the ease of quaternization. In series with the same number and orientation of heteroatoms, rate constants increase in the order X = 0requires stronger reagents and conditions methyl fluorosulfonate is sometimes used (78AHC(22)71). The 1-or 2-substituted 1,2,3-triazoles are difficult to alkylate, but methyl fluorosulfonate succeeds (7IACS2087). 

Thiadiazoles are quaternized to give 3- or mixtures of 2- and 3-alkyl quaternary salts. In 5-amino-1,2,4-thiadiazole, quaternization takes place at the 4-position (90) (64AHC(3il). 1-Substituted 1,2,4-triazoles are quaternized in the 4-position (91), and 4-substituted 1.2,4-triazoles are quaternized in the 1- or the 2-position (92) 64AHC(3)l). 

Halogeno-1,2,4-triazoles are more easily isolated, especially when the 3,5-positions are substituted. 

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. 

Halogeno-l-methyl-l,2,3-triazoles undergo substitution reactions with amines, but the 4-halogeno analogs do not. 5-Chloro-l,4-diphenyl-l,2,3-triazole with sodium cyanide in DMSO gives the cyano derivative (63JCS2032). 1-Substituted 3-chloro- and 5-chloro-l,2,4-triazoles both react with amines. 

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. 

Other amino substituted isoxazoles undergo ring-opening reactions on treatment with base. Thus the amidine derivative (249) gave the triazole (250) (64TL149), while the triazene (251) on reaction with ammonia gave the tetrazole (252) (64X461). 

Thieno[3,4-d][ 1,2,3]triazole, tetramethyl-synthesis, 6, 1015 Thieno[3,4-c][ 1,2,3]triazoles synthesis, 6, 1042 Thieno[3,4-d][ 1,2,3]triazoles reactions, 6, 1036 synthesis, 6, 1044 Thienyl radicals generation, 4, 832 Thiepane, 2-acetoxy-synthesis, 7, 574 Thiepane, 2-chloro-nucleophilic substitution, 7, 573 synthesis, 7, 574 Thiepane, 2-methyl-synthesis, 7, 573 Thiepane, 2-phenyl-synthesis, 7, 573 Thiepane, 3,3,6,6-tetramethyl-cycloaddition reactions, 7, 574 Thiepanes, 7, 547-592 applications, 7, 591... 

Triazole, 5-amino-acetylation, 5, 696 acylation, 5, 696 diazotization, 5, 97 4-substituted... 

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