Nucleophilic substitution with azide

In a discussion of the formation of the carbon-azide bond by nucleophilic substitution with azide ion at an electrophilic carbon centre, the consequences of mechanistic differences betv/een reactions at saturated, unsaturated and aromatic centres must be considered. 

On the other hand, triflation of 20 afforded 21, which underwent nucleophilic substitution with azide ion to give 25 (84% yield). Reduction of 25 and subsequent protection of the resulting amine afforded the carbamate 26 (72% yield). Treatment of 26 with base and then with sodium borohydride gave the unsaturated diol 27 in 55% overall yield from... 

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... 

Substituted 3,5-dihydro-4//-pyridazino[4,5-, ]indol-4-ones 50 <2001H(55)1105, 2002T10137> and 2,5-dihydro-l/7-pyridazino[4,5-7]indol-l-ones 52 <2006T121> have been synthesized from 5-(2-aminophenyl)pyridazin-3(2/0-ones 49 and 4-(2-aminophenyl)pyridazin-3(27/)-ones 51, respectively. For this purpose diazotization of the amino groups was followed by a nucleophilic substitution with sodium azide affording aryl azides. Upon heating of these compounds, the ring-closed products were obtained most probably via the formation of an electrophilic nitrene (Scheme 10). 

Ring-Substituted Cumyi Derivatives. In contrast with the sharp change in the kinetic order for nucleophilic substitution of azide ion at 1-phenyl-ethyl derivatives with changing aromatic ring substituent X (Fig. 2.2), there is no corresponding change from SnI to Sn2 nucleophilic substitution of azide ion at... 

Nucleophilic substitution of azide ion at (4-Me)-l-Cl is zero order in the concentration of azide ion [NJ] but, there is a strong bimolecular substitution reaction of azide ion with (4-Me)-l-S(Me)2 This change in the kinetic order for the reaction of azide ion shows that the pentavalent transition state... 

Nucleophilic Substitution at Benzyl Derivatives. The sharp break from a stepwise to a concerted mechanism that is observed for nucleophilic substitution of azide ion at X-l-Y (Figs. 2.2 and 2.5) is blurred for nucleophilic substitution at the primary 4-methoxybenzyl derivatives (4-MeO,H)-3-Y. For example, the secondary substrate (4-MeO)-l-Cl reacts exclusively by a stepwise mechanism through the liberated carbocation intermediate (4-MeO)-T, which shows a moderately large selectivity toward azide ion ( az/ s = 100 in 50 50 (v/v) water/ trifluoroethanol). The removal of an a-Me group from (4-MeO)-l-Cl to give (4-MeO,H)-3-Cl increases the barrier to ionization of the substrate in the stepwise reaction relative to that for the concerted bimolecular substitution of azide ion. The result is that both of these mechanisms are observed concurrently for nucleophilic substitution of azide ion at (4-MeO,H)-3-Cl in water/acetone solvents. These concurrent stepwise and concerted nucleophilic substitution reactions of azide ion with (4-MeO,H)-3-Cl show that there is no sharp borderline between mechanisms for substitution at primary benzylic carbon, but instead a region of overlap where both mechanisms are observed. 

Primary alkyl halides and some secondary alkyl halides can undergo SN2 nucleophilic substitution with an azide ion (Ny) to yield an alkyl azide. The azide can then be reduced with LiAlH4 to give a primary amine ... 

Racemic or achiral a-azido acids are synthesized by direct azide substitution on commercially available a-bromo carboxylic acids or by radical bromination of carboxylic acids followed by azide substitution. In general, azido acids are stored in the dark to avoid photolytic degradation with loss of nitrogen temperatures above 50 °C should be avoided. Radical a-bromination of a-branched carboxylic acids as required for the synthesis of a,a-dialkyl or a,a-diaryl amino acids is performed with A-bromosuccinimide. This is followed by nucleophilic substitution with sodium azide or other azide donors, e.g. tetrabutylannmonium azide, to produce achiral or racemic a-azido-a,a-diaIkyl or a-azido-a,a-diaryl carboxylic acids (Scheme 74).Synthesis of more sterically hindered a,a-disubstituted azido acids leads to hydroxy compounds when prolonged reaction times are required and not sufficient care is taken to operate under dry conditions and an inert atmosphere.t ... 

AUyl compounds are highly reactive towards nucleophiles and examples of dissociative (5 1) and associative (5 2) reactions, and nucleophilic substitution with rearrangement are well documented . Differentiation between these mechanisms when azide ion is the nucleophile is cften extremely difficult due to the possibility of rearrangement of the allylic azide resulting from substitution, and for this reason the relative nucleophilic strength of azide ion in allylic 5n reactions has not been delineated. 

To allow the further copolymerization of this macromonomer with other monomers, the chain-end iodine is extracted by nucleophilic substitution with sodium azide (NaN3). 

A more convenient procedure for the synthesis of (113) from (5) was later elaborated <9UOM(4l2)l>. It is based on the intramolecular version of the reaction of organoboranes with organic azides. The THF complex of 1-boraadamantane (5a) is treated with iodine in the presence of an excess of sodium azide. The iodine atom in the intermediately formed borabicycle (118) undergoes an easy nucleophilic substitution by azide ions. The subsequent anionotropic rearrangement in the borabicyclic azide (119) leads (after the oxidation of the reaction mixture) to aminoalcohol (120), which is smoothly converted to 1-azaadamantane (113). The yield of (113) in this synthesis is 40-45% based on (5a), or 20-22% based on triallylborane (Scheme 44). 

To put this working hypothesis on a more quantitative basis aromatic nucleophihc substitutions with azide as a nucleophile were tested for catalytic effects with 24 and 25. The corresponding transition states are even more delocalized than their aliphatic counterparts and thus higher rate augmentations should be expected. All or part of this favourable effect, however, can be anihilated due to an unfavourable activation entropy because the formation of the large transition state may suffer from the severe steric restrictions in the cavity of the host. As a corollary it was no surprise to find that the smaller tricyclic host 24 inhibited the substitution of 39 with azide in aqueous methanol The same reaction experienced a big rate acceleration in the... 

Azides from tosylates Nucleophilic substitution with retention of configuration... 

Scheme 30.17 The convergent synthesis of triazole dendrimers using CuAAC click chemistry, (a) CuAAC coupling reaction and (b) nucleophilic substitution with sodium azide. R = chain-end group, X = internal repeat unit. Reproduced with permission from Ref [112] 2004, john Wiley. Sons, Inc.

MBH acetates undergo smooth nucleophilic substitution with sodium azide in water under mild conditions to afford the corresponding ethyl 2-azido-methyl-3-phenylpropenoates 299 and 2-azidomethyl-3-phenylacrylonitriles 300 in excellent yields (Scheme 3.128). °... 

---