Triazenes synthesis

An already reported example of triazene synthesis by splitting of nitrogen chains involves thermal decomposition of tetrazane (obtainable by the oxidation of hydrazine, e.g., with OH radicals) (77) ... 

Scheme 5-124. Palladium-catalyzed alkynylation reaction on triazenes synthesis of cinnolines.

The so-called transdiazotizations are mechanistically related to the introduction of diazonio groups using sulfonic acid azides. An aromatic diazonium ion forms a triazene (diazoamino compound) with an aromatic amine the triazene tautomerizes and dissociates at the Na-Np bond of the original diazonium ion. This reaction is important for the synthesis of the 4-aminobiphenyl-4,-diazonium ion, which cannot be obtained by direct (mono-)diazotization of 4,4 -diaminobiphenyl (Allan and... 

The synthesis and mechanism of formation of a triazene from an arenediazonium ion and an amine with one or two aliphatic substituents (see Scheme 13-1, R = alkyl, R = H or alkyl) will be discussed in Section 13.2. Here we will briefly mention Dimroth s method (1903, 1905 a) for synthesis of wholly aliphatic triazenes (Scheme 13-6, R and R = alkyl). Dimroth obtained these by the action of Grignard reagents on alkyl azides followed by isolation via copper(i) salts. The Grignard method can also be applied for the synthesis of triazenes with an aromatic substituent by using an aryl azide. 

The tautomeric equilibrium easily explains the old observations (Noelting and Binder, 1884 Dimroth et al., 1907) that, irrespective of which of the two combinations of arenediazonium ion and primary aromatic amine was chosen for the synthesis of an asymmetrically substituted 1,3-diaryltriazene, the same mixture of two arenediazonium ions and two aromatic amines is always obtained in the acid-catalyzed hydrolysis of a triazene. 

Triazenes obtained from arenediazonium ions with secondary aliphatic or aromatic amines are not subject to tautomerism. They are used as stable sources of arenediazonium ion in organic synthesis and in technological applications. 

A variety of cleavage conditions have been reported for the release of amines from a solid support. Triazene linker 52 prepared from Merrifield resin in three steps was used for the solid-phase synthesis of aliphatic amines (Scheme 22) [61]. The triazenes were stable to basic conditions and the amino products were released in high yields upon treatment with mild acids. Alternatively, base labile linker 53 synthesized from a-bromo-p-toluic acid in two steps was used to anchor amino functions (Scheme 23) [62]. Cleavage was accomplished by oxidation of the thioether to the sulfone with m-chloroperbenzoic acid followed by 13-elimination with a 10% solution of NH4OH in 2,2,2-trifluoroethanol. A linker based on l-(4,4 -dimethyl-2,6-dioxocyclohexylidene)ethyl (Dde) primary amine protecting group was developed for attaching amino functions (Scheme 24) [65]. Linker 54 was stable to both acidic and basic conditions and the final products were cleaved from the resin by treatment with hydrazine or transamination with ra-propylamine. 

Brase S, Kobberling J, Enders D, Lazny R, Wang M, Brandtner S. Nitrogen-based linker. 3. Triazenes as robust and simple linkers for amines in solid-phase organic synthesis. Tetrahedron Lett 1999 40 2105-2108. 

A combination of the SNAr feature and the coordination ability of a copper complex has led to the development of a new O-arylation method that makes use of a triazene as an activating and directing group (Equation (2)).32,33 This protocol, though necessitating a three-step removal sequence of the triazene moiety, has been successfully applied to the total synthesis of vancomycin1 6 and extended to a solid-phase synthesis in which the triazene unit serves as an anchor to the resin.37... 

This procedure represents the most convenient synthesis of l-methyl-3-/>-tolyltriazene. Triazenes with more complex alkyl groups may be prepared from the corresponding amine2 or Grignard reagent.3... 

To this end, the diazoimidazole carboxamide compound 32 was transformed first by methylamine to the methyl-triazene derivative 39, which was reacted with 11 (". -phosgene to give the desired product 40 <2002JME5448>. In another approach, 32 was directly cyclized to the bicyclic product by using 1 C-labeled methyl isocyanate. This route allowed the synthesis of both the C-2-labeled 40 and the (7-methyl-labeled samples 41 <1997JLR371, 2002JME5448> (Scheme 13). 

E. Carvalho, J. Iley, M. J. Perry, E. Rosa, Triazene Drug Metabolites Part 15. Synthesis and Plasma Hydrolysis of Anti cancer Triazenes Containing Amino Acid Carriers , Pharm. Res. 1998, 15, 931-935. 

Triazenes are disguised diazonium ions which can be released under very mild acidic conditions. Inspired by the use of triazenes in natural product synthesis by Nicolaou et al. [127] and the pioneering work of Moore et al. [128, 129] and Tour et al. [130] in the synthesis of triazenes on a solid support and the final detachment to give iodoarenes, a whole set of triazene-based linkers has been developed (Tab. 3.10) [131]. The arene diazonium salts generated from the triazene linkers offer diverse opportunities for multifunctional cleavage. Two linkers based on tria-... 

I 3 Organic Synthesis on Polymeric Supports Tab. 3.10 Overview of triazene-based linker. 

The chemical uses of diazoazoles can be divided into two classes. The first, actually very limited, involves the applications of the diazo compounds themselves. The second one implies the use of the diazoazoles as key intermediates for the synthesis of biologically interesting systems such as triazenes, azolo-triazines and azolo-tetrazines, and azo dyes, which are useful in photographic processes or in the texile industry. 2-Diazo-4,5-dicyanoimidazole has found application as an explosive (73USP3770764). 

Nelson, J. C. Young, J. K. Moore, J. S. Solid-Phase Synthesis of Phenylacetylene Oligomers Utilising a Novel 3-Propyl-3-(benzyl-supported) Triazene Linkage, J. Org. Chem. 1996, 61, 8160-8168. 

Efficiency of the deprotection and coupling reactions are critical to the success of any iterative solid-phase synthesis. Shown in Scheme 1 is a triad of reactions for phenylacetylene oligomer synthesis trimethylsilyl deprotection,28 29 triazene unmasking of an iodobenzene,30 and the Sonogashira coupling of a terminal acetylene with an aryl iodide.31-33 Representative procedures for each step in this sequence are included at the end of this chapter. 

The tt-propylaminomethylated tether is the best identified to date because of its versatility and ease of synthesis. Although yields tend to vary depending on the side chain, the advantage of this route is that the tether is created directly from the desired monomer thus the oligomer does not have an unsubstituted capping monomer. A protocol was developed to test that all the amino sites on the bead are converted to triazenes.15 The diazonium salt was added portionwise to the DMF-resin suspension and an aliquot was removed and quenched with diethylamine to form the 3,3-diethyltriazene. If any excess of the diazonium remained, the corresponding triazene was formed and detected by gas chromatography (GC). The reaction was complete... 

Solid-phase methods are applicable to syntheses of sequence-specific oligomers and dendritic structures. The triazene chemistry developed for this specific purpose may also be useful in other types of syntheses. Further development of solid-phase syntheses of this type into combinatorial synthesis of oligomers is the next logical step. Solid-phase methods will never completely replace solution-phase approaches to oligomers, but either technique should be considered with respect to the special characteristics and requirements for the system under investigation. 

Methylation of the triazen 262 by diazomethane in ether yields 263, the structure of which follows from its unequivocal synthesis from 264 and 265.190 In methanol, minute quantities of the isomer 266 are formed as a by-product (3%) the structure of 266 is similarly confirmed by synthesis from 267 and 268 and supported by spectral data.190... 

The synthesis of monocyclic p-lactams via the ester-enolate imine condensation route has been reported to be carried out utilizing triazene esters (Scheme 54), [141], Esters were attached to benzylamine resin by a triazene linker employing the respective diazonium salts. Immobilized ester-enolates were reacted with various imines to give polymer-bound p-lactams in different substitution patterns. Traceless cleavage from the triazene linker yielded the desired p-lactams. 

Schunk and Enders [134] disclosed the first solid-phase synthesis of (5-1 actants via ester enolate-imine condensation employing an immobilized ester enolate in a simple three-step procedure (Scheme 31). The protocol showed high purity, excellent diastereoselectivity, and good yields of the product. The substrates were attached to the polymer with a Tl-triazene linker, which was cleaved traceless. The... 

Tl-triazene linker resulted in decomposition of the sensitive p-lactams. The relative configuration of p-lactams, was determined by NOE experiments to be the trans-configuration as observed in solution-phase synthesis [137]. 

Multifunctional Linkers as an Efficient Tool for the Synthesis of Diverse Small Molecule Libraries The Triazene Anchors... 

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