Azide nucleophilic substitution

Sodium azide Nucleophilic substitution of ar. nitro groups... 

The experimental evidence obtained for the azide nucleophilic substitution in fluorides 3 and 5 suggests that the reaction follows a different mechanism in each case. a-Glucopyranosyl fluoride 3 yields die substitution product 4 with inversion of the configuration at the anomeric carbon, which is die expected result for a Sn2-type reaction (Scheme 13.5). 

Nucleophilic substitution by azide ion on an alkyl halide (Sections 8 1 8 13) Azide ion IS a very good nucleophile and reacts with primary and secondary alkyl halides to give alkyl azides Phase transfer cata lysts accelerate the rate of reaction... 

Alkyl azides prepared by nucleophilic substitution of alkyl halides by sodium azide as shown m the first entry of Table 22 3 are reduced to alkylammes by a variety of reagents including lithium aluminum hydride... 

Alkyl azides prepared by nucleophilic substitution by azide ion in primary or secondary alkyl halides are reduced to primary alkylamines by lithium aluminum hydride or by catalytic hydrogenation... 

Nucleophilic substitution of the chlorine atom in 2-chloropyrazine and 2-chloroquinoxa-lines has been effected with a variety of nucleophiles, including ammonia and amines, oxygen nucleophiles such as alkoxides, sodium azide, hydrazine, sulfur containing nucleophiles, cyanide, etc., and reactions of this type are typical of the group (see Chapter 2.02). 

Studies of the solvolysis of 1-phenylethyl chloride and its p-substituted derivatives in aqueous trifluorethanol containing azide anion as a potential nucleophile provide details relative to the mechanism of nucleophilic substitution in this system. 

Aminodebromination of 4-bromo-l//-3-benzazepin-2-amine (25) with triethylamine occurs readily and results in formation of the quaternary salt 26 (see also Section 3.2.1.5.6.), whereas attempts to effect nucleophilic substitution of bromide with primary or secondary amines gives only tarry mixtures.41 The bromo group is also resistant to displacement by azide and benz-cncthiolate but undergoes substitution with thiocyanate ion in hot dimethylformamide to give the 4-thiocyanato derivative 27 rather than the thiourea by addition at the amine function. 

Azide is widely useful as a surrogate for ammonia in nucleophilic substitution reactions, due to its high nucleophilicity, low basicity, and stability towards a variety of conditions for subsequent transformations. In particular, the azidolysis of... 

P 4] This protocol was performed identically with [P 2], with the exception of the reactants and conditions. a-Bromotoluene was nucleophilically substituted in benzene to give a-azidotoluene at 70 °C (12 h) by azide coupled to a porous polymer resin [3],... 

Tetranitro derivative 94 (y-TACOT Section 12.10.15.5) treated with sodium azide in DMSO gives 83% yield of a single symmetrical diazido dinitro derivative 81 resulting from nucleophilic substitution of an equivalent pair of nitro groups by the azide anion (Equation 5) <1996JOC5801>. 

Dichlorooxadiazolo[3,4-3]pyrazine 181 forms the tricyclic tetrazole derivative 182 on reaction with sodium azide (Equation 44). The 7-azido group readily undergoes nucleophilic substitution <1997CHE977>. 

Nucleophilic substitution of the chloropyridazine 166 with sodium azide in DMF is followed by cyclization to give the fused tetrazole 167 (Equation 41) <1997JHC39>. 

A way to introduce the primary amino group directly onto the selenophene ring is via the azido compound, obtained by nucleophilic substitution of the bromo derivative with sodium azide. Useful transformations of the azido group are shown in Scheme 12.117 The amino aldehyde (109) is a suitable starting material for the preparation of selenolo[3,2-b]pyridine (110) by the Friedlander reaction.138 Not only can the azido be reduced to an amino... 

The direct, stereoselective conversion of alkynes to A-sulfonylazetidin-2-imines 16 by the initial reaction of copper(l) acetylides with sulfonyl azides, followed, in situ, by the formal [2+2] cycloaddition of a postulated A-sulfonylketenimine intermediate with a range of imines has been described <06AG(E)3157>. The synthesis of A-alkylated 2-substituted azetidin-3-ones 17 based on a tandem nucleophilic substitution followed by intramolecular Michael reaction of primary amines with alkyl 5-bromo-4-oxopent-2-enoates has been... 

In reactions with azides, ketones are directly converted to 5-hydroxytriazolines. Ketone enolate 247, generated by treatment of norbornanone 246 with LDA at 0°C, adds readily to azides to provide hydroxytriazolines 248 in 67-93% yield. Interestingly, l-azido-3-iodopropane subjected to the reaction with enolate 247 gives tetracyclic triazoline derivative 251 in 94% yield. The reaction starts from an electrophilic attack of the azide on the ketone a-carbon atom. The following nucleophilic attack on the carbonyl group in intermediate 249 results in triazoline 250. The process is completed by nucleophilic substitution of the iodine atom to form the tetrahydrooxazine ring of product 251 (Scheme 35) <2004JOC1720>. 

It is more difficult to interpret micellar effects upon reactions of azide ion. The behavior is normal , in the sense that k /kw 1, for deacylation, an Sn2 reaction, and addition to a carbocation (Table 4) (Cuenca, 1985). But the micellar reaction is much faster for nucleophilic aromatic substitution. Values of k /kw depend upon the substrate and are slightly larger when both N 3 and an inert counterion are present, but the trends are the same. We have no explanation for these results, although there seems to be a relation between the anomalous behavior of the azide ion in micellar reactions of aromatic substrates and its nucleophilicity in water and similar polar, hydroxylic solvents. Azide is a very powerful nucleophile towards carboca-tions, based on Ritchie s N+ scale, but in water it is much less reactive towards 2,4-dinitrohalobenzenes than predicted, whereas the reactivity of other nucleophiles fits the N+ scale (Ritchie and Sawada, 1977). Therefore the large values of k /kw may reflect the fact that azide ion is unusually unreactive in aromatic nucleophilic substitution in water, rather than that it is abnormally reactive in micelles. 

Table 6 Tetrazolopyridazines, -pyrimidines, and -pyrazines prepared by nucleophilic substitution of haloazines by azide anion...

Tandem nucleophilic substitution-[2+3] cycloaddition reaction of 4-bromo- and 4-toluenesulfonyloxy aldehydes 77 with sodium azide in DMF at 50 °C affords excellent yields (>80%) of substituted pyrrolo[.2.3.4]oxatriazoles 78 (Scheme 8) <2002HAC307>. 

Lifetimes of the ionic intermediates of nucleophilic substitution are generally correlated to the pathways followed under given reaction conditions. Information on the lifetimes of ionic intermediates formed by bromine addition to olefins in methanol, as determined by the azide clock method, do not allow the different reaction pathways to be distin-... 

The activating effect of the azide makes the fluorine labile, so that there is a risk of excess azide incorporation when attempting preparation by nucleophilic substitution of bromofluorocarboxylates, giving more explosive products than anticipated. 

Azide ion is a modest leaving group in An + Dn nucleophilic substitution reactions, and at the same time a potent nucleophile for addition to the carbocation reaction intermediate. Consequently, ring-substituted benzaldehyde g m-diazides (X-2-N3) undergo solvolysis in water in reactions that are subject to strong common-ion inhibition by added azide ion from reversible trapping of an o -azido carbocation intermediate (X-2 ) by diffusion controlled addition of azide anion (Scheme... 

Onium salts, such as tetraethylammonium bromide (TEAB) and tetra-n-butylammonium bromide (TBAB), were also tested as PTCs immobilized on clay. In particular, Montmorillonite KIO modified with TBAB efficiently catalyzed the substitution reaction of a-tosyloxyketones with azide to a-azidoketones, in a biphasic CHCI3/water system (Figure 6.13). ° The transformation is a PTC reaction, where the reagents get transferred from the hquid to the solid phase. The authors dubbed the PTC-modified catalyst system surfactant pillared clay that formed a thin membrane-hke film at the interface of the chloroform in water emulsion, that is, a third liquid phase with a high affinity for the clay. The advantages over traditional nucleophilic substitution conditions were that the product obtained was very pure under these conditions and could be easily recovered without the need for dangerous distillation steps. 

Nucleophile substitution of the T1 resin synthesis of phenols, biaryls, alkyl arenes, azides, aromatic hydrazines, halides, ester, azo compounds cinnolines, benzotriazoles [129-137, 140, 141]... 

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