Azide ions

Bunton C A, Moffatt J R and Rodenas E 1982 Abnormaiiy high nucieophiiicity of miceiie-bound azide ion J. Am. Chem. Soc. 104 2653-5... 

Azide ion ( N=N=N ) Sodium azide IS a reagent used for carbon-nitrogen bond formation The product IS an alkyl azide... 

Azide ion Alkyl halide Alkyl azide Halide ion... 

Azide ion ( N=N=N ) is a good nucleophile and an even weaker base than cyanide It reacts with secondary alkyl halides mainly by substitution... 

The conjugate acid of azide ion IS called hydrazoic acid (HN3) It has a p/C of 4 6 and so IS similar to acetic acid in Its acidity... 

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... 

Nucleophilic ring opening of epoxides by ammonia (Section 16 12) The strained ring of an epoxide is opened on nucleo philic attack by ammonia and amines to give 3 ammo alcohols Azide ion also re acts with epoxides the products are p azido alcohols... 

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... 

Solvent for Displacement Reactions. As the most polar of the common aprotic solvents, DMSO is a favored solvent for displacement reactions because of its high dielectric constant and because anions are less solvated in it (87). Rates for these reactions are sometimes a thousand times faster in DMSO than in alcohols. Suitable nucleophiles include acetyUde ion, alkoxide ion, hydroxide ion, azide ion, carbanions, carboxylate ions, cyanide ion, hahde ions, mercaptide ions, phenoxide ions, nitrite ions, and thiocyanate ions (31). Rates of displacement by amides or amines are also greater in DMSO than in alcohol or aqueous solutions. Dimethyl sulfoxide is used as the reaction solvent in the manufacture of high performance, polyaryl ether polymers by reaction of bis(4,4 -chlorophenyl) sulfone with the disodium salts of dihydroxyphenols, eg, bisphenol A or 4,4 -sulfonylbisphenol (88). These and related reactions are made more economical by efficient recycling of DMSO (89). Nucleophilic displacement of activated aromatic nitro groups with aryloxy anion in DMSO is a versatile and useful reaction for the synthesis of aromatic ethers and polyethers (90). 

CPB1457), whilst with azide ion the chloro compound (107) underwent ring opening and reclosure to give the 2-tetrazolyl-3-aminopyridine (108) (74CR(C)(278)l42l). 

Halogen atoms on benzazole rings can be activated toward nucleophilic displacement by electron-withdrawing groups. Thus azide ion displaces chlorine from 5-chloro-4-nitro- and 4-chloro-7-nitro-benzofuroxan (65JCS5958). 

The reactions of 3-unsubstituted iso.xazolium salts (123) with hydroxide, alkoxide, cyanide and azide ions have also been studied, and they can in general be rationalized in terms of the ketoketenimine intermediate (124). The results of these reactions are summarized below. The application of such reactions to 3-unsubstituted isoxazolium salts bearing substituents other than alkyl and aryl groups has received little attention, but 5-aminoisoxazolium salts have been studied (74CB13). 

The 3-substituents in 3-nitro- and 3-phenylsulfonyl-2-isoxazolines were displaced by a variety of nucleophiles including thiolate, cyanide and azide ions, ammonia, hydride ions and alkoxides. The reaction is pictured as an addition-elimination sequence (Scheme 54) (72MI41605, 79JA1319, 78JOC2020). 

Apparent nucleophilic attack on large, fully unsaturated rings may occur by way of attack on a valence tautomer, such as the reaction of oxepin with azide ion. Attack on the oxanorcaradiene valence tautomer leads to ring opening of the three-membered ring, and formation of 5-azido-6-hydroxy-l,3-cyclohexadiene (Section 5.17.2.2.4). 

The commonest of these for oxirane opening are amines and azide ion [amide ions promote isomerization to allylic alcohols (Section 5.05.3.2.2)]. Reaction with azide can be used in a sequence for converting oxiranes into aziridines (Scheme 49) and this has been employed in the synthesis of the heteroannulenes (57) and (58) (80CB3127, 79AG(E)962). 

Diphenylthiirene 1-oxide reacts with hydroxylamine to give the oxime of benzyl phenyl ketone (79JA390). The reaction probably occurs by addition to the carbon-carbon double bond followed by loss of sulfur monoxide (Scheme 80). Dimethylamine adds to the double bond of 2,3-diphenylthiirene 1,1-dioxide with loss of sulfur dioxide (Scheme 81) (75JOC3189). Azide ion gives seven products, one of which involves cleavage of the carbon-carbon bond of an intermediate cycloadduct (Scheme 81) (80JOC2604). 

If it is assumed that ionization would result in complete randomization of the 0 label in the caihoxylate ion, is a measure of the rate of ionization with ion-pair return, and is a measure of the extent of racemization associated with ionization. The fact that the rate of isotope exchange exceeds that of racemization indicates that ion-pair collapse occurs with predominant retention of configuration. When a nucleophile is added to the system (0.14 Af NaN3), k y, is found to be imchanged, but no racemization of reactant is observed. Instead, the intermediate that would return with racemization is captured by azide ion and converted to substitution product with inversion of configuration. This must mean that the intimate ion pair returns to reactant more rapidly than it is captured by azide ion, whereas the solvent-separated ion pair is captured by azide ion faster than it returns to racemic reactant. 

An example with the characteristics of the coupled displacement is the reaction of azide ion with substituted 1-phenylethyl chlorides. Although the reaction exhibits second-order kinetics, it has a substantially negative p value, indicative of an electron deficiency at the transition state. The physical description of this type of activated complex is the exploded S 2 transition state. 

Table 5.7 lists the nucleophilic constants for a number of species according to this definition. It is apparent from Table 5.7 that nucleophilicity toward methyl iodide does not correlate directly with basicity. Azide ion, phenoxide ion, and bromide are all equivalent in nucleophilicity but differ greatly in basicity. Conversely, azide ion and acetate ion are... 

In fee absence of fee solvation typical of protic solvents, fee relative nucleophilicity of anions changes. Hard nucleophiles increase in reactivity more than do soft nucleophiles. As a result, fee relative reactivity order changes. In methanol, for example, fee relative reactivity order is N3 > 1 > CN > Br > CP, whereas in DMSO fee order becomes CN > N3 > CP > Br > P. In mefeanol, fee reactivity order is dominated by solvent effects, and fee more weakly solvated N3 and P ions are fee most reactive nucleophiles. The iodide ion is large and very polarizable. The anionic charge on fee azide ion is dispersed by delocalization. When fee effect of solvation is diminished in DMSO, other factors become more important. These include fee strength of fee bond being formed, which would account for fee reversed order of fee halides in fee two series. There is also evidence fiiat S( 2 transition states are better solvated in protic dipolar solvents than in protic solvents. 

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. ... 

Consider these results with respect to the mechanisms outlined in Fig. 5.6 (p. 274). Delineate the types of substituted 1-arylethyl halides which react with azide ion according to each of these mechanisms on the basis of the data given above. 

The azidohydrins obtained by azide ion opening of epoxides, except for those possessing a tertiary hydroxy group, can be readily converted to azido mesylates on treatment with pyridine/methanesulfonyl chloride. Reduction and subsequent aziridine formation results upon reaction with hydrazine/ Raney nickel, lithium aluminum hydride, or sodium borohydride/cobalt(II)... 

Replacement of one tosyloxy group m 2-fluoro-2-nitro-l,3-propanediol ditosylate by azide ion occurs easily [S5] (equation 75)... 

The preparation of a tnflate salt may include the decomposition of tnflyl azide by azide ion Tnflyl azide can be prepared by the reaction of the azide ion with tnfluoromethanesulfonyl fluonde or tnfluoromethanesulfomc anhydnde [18] (equauonlS) Anotherone stepprocedureusesaquatemaryammoniumcountenon [J9] (equation 15) This tnflate can react with primary halides to form tn fluoromethyl sulfones [19 (equation 16) (Table 7)... 

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