Azide ions benzyl derivatives

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. 

For the recombination of a-phenylethyl cations with strong nucleophiles, Richard and Jencks (1984a,b,c) obtained good Y-T correlations with the same r value of 1.15 as observed for the solvolysis (Fig. 35). The p value of -2.7 for the bimolecular substitution reaction of azide ion with 1-phenylethyl derivatives is significantly more positive than the value of p = -5.7 for the solvolysis reaction. This shows that there is a smaller development of positive charge in the transition state for the reaction of azide ion than for solvolysis. It is consistent with a coupled concerted reaction with a transition state in which positive charge development at the benzylic carbon is neutralized by bonding to azide ion. 

Acid-catalyzed hydrolysis of 65a yields tram diol as the only detectable product,69 and this diol product is rationalized by axial attack of water on carbocation 66a. Since the lifetime of a simple benzyl carbocation is very short, an argument might be made that the trans diol is instead formed by an A-2 mechanism. However, we have also synthesized the methoxy derivative 65b, and its acid-catalyzed hydrolysis also yields >98% trans diol.70 The lifetime of carbocation 65b is sufficiently long that it can be captured, subsequent to its rate-limiting formation, by azide ion. This result clearly shows that the trans diol product from acid-catalyzed hydrolysis 65b is formed by axial attack of water on a discrete carbocation (66b). 

Synthesis from D-glucuronolactone Synthesis of bulgecinine from D-glucuro-nolactone derivative 27 has been reported (Scheme 4). Triflation of the lactone 27 followed by nucleophilic displacement of the triflate group with azide ion and then hydrogenation and protection with benzyl chloroformate produced 28. Conversion of 28 to the unstable aldehyde 29 followed by reduction in situ by sodium borohydride afforded the crystalline diol 30, with no epimerization at C-5. Selective mesylation of 30 gave the mesylate... 

Tetra-O-benzyl-a-D-glucopyranosyl azide was obtained by nucleophilic displacement reaction of the corresponding a-glucosyl phosphate with azide ion under phase-transfer catalysis conditions. Oxidation of unprotected D-glycopyranosyl azides (with NaOQ, NaHCOj, catalytic TEMPO, H2O) afforded the corresponding D-glycopyraniuronosyl azides, which were isolated as the O-acetylated methyl ester derivatives in good yields. ... 

All nuclear nucleophilic substitutions on derivatives of compound 4 have involved the replacement of a substituent at position 7 (the equivalent of the y -position in pyridine). In the 7-chloro derivative 244, replacement is possible by methoxide ion,151 by ammonia (with some rearrangement)192 and by amines,151 and by thiourea to give the sulfide (245).151 Substituted 7-chloro derivatives undergo replacement by benzyl oxide ion to give a 7-benzyloxy derivative155,220 and by azide,153 hydrazine,216 hydrosulfide (to give the 7-thione166), and methyl thiolate.220 Some of these compounds carry D-ribofuranosyl benzoate substituents on N-2 or N-3, and methoxide ion... 

Aube and co-workers have found that enolizable ketones react with benzyl azide in triflic acid to yield /V-(phenylamino)-methylated products [Eq. (5.354)]. The transformation is an aza-Mannich reaction interpreted with the involvement of the Mannich reagent A -phenyl iminium ion 295 formed in situ in a Schmidt rearrangement. Cyclic tertiary alcohols react with alkyl azides in triflic acid to yield N-alkylamines (296, 297)983 [Eq. (5.355)]. The Schmidt rearrangement was used to transform Merrifield resin into amino-polystyrene resin by reacting the azido derivative in excess triflic acid (CH2CI2, 0°C).984... 

---