Azide ion reactions

The nitrogen heterocycles, aziridines, can be made by displacement of an alcohol by an amine after activation. In their synthesis of the antitumour and antibiotic compound 30, whose active region is the aziridine, J. P. Michael and group opened the cyclic sulfite 28 with azide ion. Reaction occurred at the allylic position and with inversion. Activation of the alcohol as a mesylate gave 29 and reduction of the azide to an amine was followed by base-catalysed cyclisation, again with inversion.4... 

The activation entropies are mostly negative, as expected for reactions in which one species is formed from two. The differences between the values for the isomers are generally low. The most interesting feature of these values is the large increase in the activation entropy when the azide ion reaction is conducted in dimethylformamide instead of in ethanol. 

L=(2-pyridylmethyl)iminodiacetate ion] with thiocyanate and azide ions, reactions which involve replacement of the basal water molecule in a cw-position to V=0) gave data for both the rate of formation (kr) and the rate of dissociation (kd), as shown in Table An associative mechanism is favoured for the formation reactions. 

In some cases when oxidising conditions are required, milder oxidants may be needed, because the hydroxyl radical can react with the solute forming adducts as well as via electron transfer. Hydroxyl radicals can be converted into milder (one-electron) oxidants by the addition of halides, thiocyanate or azide ions (reactions 8.15-8.17). In fact, halide radical reactions occur in atmospheric chemistry, particularly in urban cloud droplets, as well as in marine water radical reactions [29]. 

The rates of 5 2 and 2 reactions of several fluorinated alkyl bromides and iodides have been measured in methanol and in DMSO using azide ion and methoxide ion as the nucleophile (base). The results demonstrate the effect of changing the nucleophile, the solvent, the leaving group, and a- and -fluorine substituents on the rates of these reactions. MP2/6-3 l-l-G(d,p)-LANL2DZ level calculated AG and transition states found for both the 5 2 and the 2 reactions are consistent with the experimental results. The azide ion reactions are almost exclusively 5 2 processes, whereas the methoxide ion reactions... 

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... 

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). 

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). 

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. 

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. ... 

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)... 

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)... 

If the intermediate is very unstable, large rate constants may be measured in this way. Thus, Amyes and Jencks studied the hydrolysis of a-azidoethers (Ns", the azide ion, being the common ion), finding (because k i had been independently measured) k2 values in the range 10 to 10 ° M s for the reaction with water. 

Azides have been shown to react with itniniutn salts to give addition products. The same product is obtained if the iminium salt is treated with azide ion or if the enamine is treated with hydrazoic acid 14). The yields of the products were all very high (85-95 %). The interest in this reaction centers on the fact that the azides react with isonitriles to give substituted tetrazoles (83) 44). 

The molecule has an almost linear N3 group and an angle C-N-N of 112.4° (Fig. II.4a).( ) The (linear) azide ion, N3", is isoelectronic with N2O, CO2, OCN", etc. and forms numerous coordination complexes by standard ligand replacement reactions. Various coordination modes have been established, including end-on bridging... 

The disulfide has a special interest as the catalyst in the carbon disulfide-catalyzed iodine-azide reaction. No perceptible nitrogen evolution will take place in a solution containing iodine and azide ions without the presence of a catalyst. Thiosulfates, sulfides, and many other sulfur compounds act as catalysts. In 1922 Browne et found that carbon disulfide is a powerful catalyst in this... 

The 5-alkylamino-l,2,3,4-thiatriazoles are cleaved by alkali into an azide ion and an isothiocyanate. The same reaction takes place to some extent also when the substituent is an aryl group, so that we have to deal with two competing reactions [Eq. (17)]. According to Lieber... 

Properties attributed to the intermediate complex from reaction of 4-nitrofluorobenzene with azide ion were found later to be due to an artifact resulting from photolytic decomposition of the... 

The effect of a substituent may be substantially modified by fast, concurrent, reversible addition of the nucleophile to an electrophilic center in the substituent. Ortho- and para-CS.0 and pam-CN groups have been found by Miller and co-workers to have a much reduced activating effect on the displacement of halogen in 2-nitrohaloben-zenes with methoxide ion [reversible formation of hemiacetal (143) and imido ester anions (144)] than with azide ion (less interaction) or thiocyanate (little, if any, interaction). Formation of 0-acyl derivatives of 0x0 derivatives or of A-oxides, hydrogen bonding to these moieties, and ionization of substituents are other examples of reversible and often relatively complete modifications under reaction conditions. If the interaction is irreversible, such as hydrolysis of a... 

Azide synthesis (Section 24.6) A method for preparing amines by S 2 reaction of an alkyl halide with azide ion, followed by reduction. 

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

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