Azide ion reaction with

Neopentyl (2,2-dimethylpropyl) systems are resistant to nucleo diilic substitution reactions. They are primary and do not form caibocation intermediates, but the /-butyl substituent efiTectively hinders back-side attack. The rate of reaction of neopent>i bromide with iodide ion is 470 times slower than that of n-butyl bromide. Usually, tiie ner rentyl system reacts with rearrangement to the /-pentyl system, aldiough use of good nucleophiles in polar aprotic solvents permits direct displacement to occur. Entry 2 shows that such a reaction with azide ion as the nucleophile proceeds with complete inversion of configuration. The primary beiuyl system in entry 3 exhibits high, but not complete, inversiotL This is attributed to racemization of the reactant by ionization and internal return. 

Entry 4 shows that reaction of a secondary 2-octyl system with the moderately good nucleophile acetate ion occurs wifii complete inversion. The results cited in entry 5 serve to illustrate the importance of solvation of ion-pair intermediates in reactions of secondary substrates. The data show fiiat partial racemization occurs in aqueous dioxane but that an added nucleophile (azide ion) results in complete inversion, both in the product resulting from reaction with azide ion and in the alcohol resulting from reaction with water. The alcohol of retained configuration is attributed to an intermediate oxonium ion resulting from reaction of the ion pair with the dioxane solvent. This would react until water to give product of retained configuratioiL When azide ion is present, dioxane does not efiTectively conqiete for tiie ion-p intermediate, and all of the alcohol arises from tiie inversion mechanism. ... 

Curtius rearrangement (Section 24.6) The conversion of an acid chloride into an amine by reaction with azide ion, followed by heating with water. 

A number of studies have been reported concerning azide-isocyanide condensations to give tetrazoles. Early work by Beck and co-workers 18, 19) describes the addition of various isocyanides to metal azido species [Au(N3)4]", [Au(N3)2]", Au(PPh3)N3, and M(PPh3)2(N3)2, M = Pd, Pt, Hg. The products are carbon-bonded tetrazolato-metal complexes. It is not known whether metal isocyanide complexes are intermediates in these reactions. More recently inverse reactions with azide ion addition to metal isocyanide complexes were carried out, with similar results. From... 

Examples of the three mechanistic types are, respectively (a) hydrolysis of diazonium salts to phenols89 (b) reaction with azide ion to form aryl azides90 and (c) reaction with cuprous halides to form aryl chlorides or bromides.91 In the paragraphs that follow, these and other synthetically useful reactions of diazonium intermediates are considered. The reactions are organized on the basis of the group that is introduced, rather than on the mechanism involved. It will be seen that the reactions that are discussed fall into one of the three general mechanistic types. 

Absolute values of the rate constants ks (s ) and kp (s ). In most cases these rate constants were determined from the values of kaz/ks (M 1) or kaz/kp (M-1) for partitioning of the carbocation between reaction with azide ion and solvent, by using the diffusion-limited reaction of azide ion, kaz = 5 x 109m 1s, as a clock for the slower reactions of solvent.7 8 13 32 82... 

The values, ranging from 3 to 6 M are seven orders of magnitude smaller than the selectivity observed for activation limited reactions with stable cations, and can be used as evidence that the reaction with azide ion is a diffusion controlled process. Choosing a value for the rate constant for a diffusion-limited... 

The Z-alkene ( ) was subjected to the same sequence (Scheme 4). The triflate ( ) was easily obtained, but in this case reaction with azide ion gave directly the diazoester (22). Molecular models show that the triazoline corresponding to (19) has severe steric interactions and is more accessible to deprotonation (cf. ref. 23). 

The transition states for the stepwise (fej, Fig. 2.3) and concerted (fecon) reactions of (4-MeO,X)-3-Y lie at distinct well-separated positions on the More O Ferrall diagram and show different sensitivities to changes in solvent polarity, meta substituents X at the aromatic ring, and the leaving group Y. For example, in 50 50 (v/v) water/trifluoroethanol (4-MeO,H)-3-Cl reacts with azide ion exclusively by a stepwise mechanism through the primary carbocation intermediate (4-MeO,H)-3" with a selectivity for reaction with azide ion and solvent of feaz/ s = 25 However, two-thirds of the azide ion substitution product obtained from the reaction of (4-MeO,H)-3-Cl in the less polar solvent 80 20 acetone/water forms by concerted bimolecular substitution and only one-third forms by trapping of the carbocation intermediate (4-MeO,H)-3 with a selectivity of k z/h = 8 The preferred... 

Amino-substituted selenophenes are in general unstable compounds, and are conveniently isolated as IV-acetyl or iV-formyl derivatives. An ortho situated electron-attracting substituent such as acetyl, formyl or nitro renders the amino compounds stable. Derivatives of this type can be diazolized and the resulting diazonium salts converted into azides (by reaction with azide ion) (75CR(C)(281)317) and selenocyanates (by reaction with selenocyanide ion) (79BSF(2)237). 3-Acetamidoselenophene can be thiocyanated or selenocyanated in the 2-position by treatment with bromine and potassium thiocyanate or potassium selenocyanate, respectively (78TL1797). 

Some new 5-(benzylamino)thiatriazoles have been prepared by standard methods.12 5-(Tetra-0-acetyl-/T-D-glucopyranosylamino)-thia-triazole was prepared by the action of HN02 on 4-(tetra-0-acetyl-/3-D-glucopyranosyl)thiosemicarbazide as well as from hydrogen azide and tetra-0-acetyl-/J-D glucopyranosyl isothiocyanate.62 Substituted 5-aminothiatriazoles may be obtained from C-sulfonylthioformamides on reaction with azide ion.63... 

Figure 5.5 Correlation between stability, measured by solvolysis rate in 80 percent aqueous acetone, and selectivity, determined by relative rate of reaction with azide ion (kN) and water (kw), for carbocations derived from alkyl chlorides. Reprinted with permission from D. J. Raber, J. M. Harris, R. E. Hall, and P. v. R. Schleyer, J. Amer. Chem. Soc., 93, 4821 (1971). Copyright by the American Chemical Society.

Richard has also shown that intrinsic barriers for carbocation reactions depend not only on the extent of charge delocalization but to what atoms the charge is delocalized. In a case where values of pifR for calculation of A were not available, comparisons of rate constants for attack of water kH2o with equilibrium constants for nucleophilic reaction with azide ion pKAz for 65-67 showed qualitatively that delocalization to an oxygen atom leads to a lower barrier than to an azido group which is in turn lower than to a methoxyphenyl substituent.226... 

As has been discussed elsewhere, Fig. 7 demonstrates the basis for using reactions with azide ion as a clock for determining values of log kH2o in the range pATR = -5 to —15. However, the discussion above cautions against too narrow an interpretation of this figure. The correlations apply to benzhydryl cations and trityl cations and, as we have seen, other families of cations can lead to less ideal dependences of kn2o and, presumably, kAz on p/fR. 

The dilemma presented by these conflicting results was resolved by TaShma and Rappoport.265 They pointed out that the apparent dependence of kAz/ knl0 upon the reactivity of the carbocation arose because even the most stable cation reacting with azide ion did so at the limit of diffusion control. Thus while kn2o remained dependent on the stability of the cation in the manner illustrated in Fig. 7 the rate constant for the azide ion remained unchanged. Thus the most stable cation formed in the solvolysis reactions was the trityl ion, for which direct measurements of kn2o = 1 -5 x 105 s 1 and kAz = 4.1 x 109 now show that even for this ion the reaction with azide ion is diffusion controlled.22... 

Selectivity of Mesylates in Aqueous Diglyme in their Reaction with Azide Ion, Borohydride Ion and Water ... 

An addition—elimination mechanism (equation 17) appears to be operative in such reactions with azide ion, since it has been found that the Br/ ci rate ratios for a series of derivatives of ArS02CH=CHHai are very similar . This result indicates that C—bond formation precedes the C— Hal bond breaking step. The stereochemistry of the substitution depends on the specific addition—elimination pathway involved. In particular, the lifetime of a carbanionic intermediate is important in relation to the configuration of the final product and this is discussed in detail in section I1I.B.2. 

As expected, substitution by azide ion occurs more readily when the alkyl substrate bears electron-withdrawing groups. For example phenacyl bromide and its derivatives give high yields of azides when treated with sodium azide in the cold °. Secondary alkyl substrates undergo Sj,2 reactions with azide ion ° ° but with less facility than primary alkyl substrates in accordance with the normal polar influences and primary steric eflfects in reactions . Selective substitution is therefore possible and this has been effectively applied in carbohydrate and steroid synthesis (sections II.B.5,6). These effects are also exemplified in the alicyclic series where it has been reported that menthyl halides and 2-methylcyclohexyl halides afford unsatisfactory yields of azide ° . The unsubstituted alicyclic azides, however, are obtained in good yields by the procedures outlined above(Table 1). 

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