1,2,4-Triazole, conjugative

The copper-catalyzed alkyne-azide cycloaddition is a very useful methodology for the preparation of triazole libraries. Thus, a library of triazole amphiphiles with a variety of functional polar heads and hydrophobic or superhydrophobic tails [97], a 96-product-sized library of 1,2,3-triazoles from organic azides and terminal alkynes [98], and a small hbrary of triazole-conjugated coumarins have been synthesized [99]. 

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. 

Synthesis of cross-conjugated mesomeric betaines containing l-oxo-l//-pyrazolo[l,2-tf]pyrazol-4-ium-3-olate, 1-oxo-1 //-pyrazolof 11.2,4]triazol-4-ium-3-olate, 7-oxo-7//-pyrazolo[l,2-tf][l,2,4]triazol-4-ium-5-olate, 7-oxo-7.//-pyrazolo[ 1.2-//][ 1.2.3 ]mazol-4-ium-5-olate, 3-oxo-3//-pyrazolo[l,2- ][l,2,3,5]thiatriazol-8-ium-l-olate, and 2-hydroxy-pyrazolof 1.2-//][ 1.2.5]m.izin-5-iumH-olate structures was duly covered in CHEC-II(1996) <1996CHEC-II(8)747> and... 

Reaction 60 shows the reaction of an alkyne with an azide to form a triazole ring in the presence of a Cu(I) catalyst. See Chapter 17, Section 4 for additional details on the use of this conjugation reaction. 

Figure 17.15 The small carboxylate-alkyne compound 4-pentynoic acid can be used to modify proteins at their amine groups with EDC to provide alkyne sites for click chemistry-mediated conjugation. The subsequent reaction of an azido-PEG-modified gold nanoparticle with the alkynyl-protein in the presence of Cu1+ yields the triazole-coupled protein.

Glowka et al. studied two tetrahydro[l,2,4]triazolo[4,3- ]pyrimidine derivatives 66a and 66b by X-ray diffraction <1994JCX375>. In the solid state, both molecules had the same conformation and were found to be packed in similar manner. The triazole rings proved to be planar, and the conjugation of the Jt-electrons with the lone pair of the N-8 atom was assumed to be the reason of the sofa conformation of the saturated six-membered ring. 

A.W. Grice, A. Tajbakhsh, P.L. Burn, and D.D.C. Bradley, A blue-emitting triazole-based conjugated polymer, Adv. Mater., 9 1174-1178, 1997. 

Plant. Amitrole is transformed in plants forming the conjugate p (3-amino-l,2,4-tria-zol-l-yl)-a-alanine (Humburg et ah, 1989) and/or 3-(3-amino-s-triazole-l-yl)-2-aminopropionic acid (Duke et al, 1991). Amitrole is metabolized in Canada thistle Cirsium arvense L.) to three... 

Synthesis was directed towards metabolic stability and this was found in the bis-triazole series of compounds. Metabolic stability is achieved by the relative resistance of the triazole moiety to oxidative attack, the presence of halogen functions on the phenyl grouping, another site of possible oxidative attack, and steric hindrance of the hydroxy function, a site for possible conjugation. 

Sodium azide also adds to olefins of this t3rpe to give w-triazoles in fairly good yields. A mechanism involving nucleophilic displacement of the substituent X by azide, followed by cyclization of the vinyl azide in the presence of azide ions, has been suggested. An alternative mechanism involves conjugate addition of azide to the double bond, cyclization of the resulting anion, and aromatization. 

J0rgensen [111] and Vicario [112] independently described the conjugate addition of both triazole and tetrazole based nucleophiles to a,P-unsaturated aldehyde substrates as an alternative method for C-N bond formation. These reactions were catalysed by the diarylprolinol and imidazolidinone scaffolds with equal efficiency showing the complementarity and efficacy of both these catalyst architectures. In addition, Jprgensen has also shown succinimide to be an effective Michael donor (see Sect. 2.3.5 Scheme 49 for further details) [113]. 

Different synthetic routes have been used to prepare these carbenes (Scheme 8.6). The most common procedure is the deprotonation of the conjugate acid. In early experiments, sodium or potassium hydride, in the presence of catalytic amounts of either f-BuOK or the DMSO anion were used. ° Then, Herrmann et al. showed that the deprotonation occurs much more quickly in liquid ammonia as solvent (homogeneous phase), and many carbenes of type IV have been prepared following this procedure. In 1993, Kuhn and Kratz" developed a new and versatile approach to the alkyl-substituted N-heterocyclic carbenes IV. This original synthetic strategy relied on the reduction of imidazol-2(3//)-thiones with potassium in boiling tetrahydrofuran (THF). Lastly, Enders et al." reported in 1995 that the 1,2,4-triazol-5-ylidene (Vila) could be obtained in quantitative yield from the corresponding 5-methoxy-l,3,4-triphenyl-4,5-dihydro-l//-l,2,4-triazole by thermal elimination (80 °C) of methanol in vacuo (0.1 mbar). 

The symmetrical use of a second triazole removes an asymmetric centre, so obviating the need for resolution. Triazole and hydroxyl groups keep overall lipophilicity low. The hydroxyl is sterically hindered, hence does not undergo conjugation. 

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