Sodium azide, displacement reactions

There are a lot of preparation methods for aliphatic diazides. The most common and convenient method is the displacement reaction of dihalogenerated hydrocarbons and sodium azide. The reaction is displayer in below general expression. 

Reaction of 5-chloro-l,2,4-triazolo[l,5-c]pyrimidines (165) with sodium hydroxide, thiourea, or hydrazine hydrate (79AJC1585) or with sodium azide (85EUP152841) also caused the displacement of the chlorine atom to... 

In the original work (72), the authors stated that heating of 42 with excess sodium iodide did not result in further exchange. The extensive studies of Stevens and co-workers (96, 97) on the displacement reactions of compounds much related to 40, indicate that the C-4 sulfonate group can indeed be displaced by various nucleophiles. In fact compound 42 and its C-4 epimer (43) (d-threo) have been subjected to displacement reactions with benzoate (38), acetate and azide (98) ions to give the corresponding C-4 inverted products. 

Nucleophilic Displacement Reactions in Carbohydrates. Part XI. Reaction of Methyl 6-Deoxy-2,3-O-isopropylidene-4-O-methyl-sulphonyl-a-L-talopyranoside with Sodium Azide A Synthesis of L-Perosamine (4-Amino-4,6-dideoxy-L-mannose) Derivatives, J. S. Brimacombe, O. A. Ching, and M. Stacey, J. Chem. Soc. C, (1969) 1270-1274. 

The aziridine aldehyde 56 undergoes a facile Baylis-Hillman reaction with methyl or ethyl acrylate, acrylonitrile, methyl vinyl ketone, and vinyl sulfone [60]. The adducts 57 were obtained as mixtures of syn- and anfz-diastereomers. The synthetic utility of the Baylis-Hillman adducts was also investigated. With acetic anhydride in pyridine an SN2 -type substitution of the initially formed allylic acetate by an acetoxy group takes place to give product 58. Nucleophilic reactions of this product with, e. g., morpholine, thiol/Et3N, or sodium azide in DMSO resulted in an apparent displacement of the acetoxy group. Tentatively, this result may be explained by invoking the initial formation of an ionic intermediate 59, which is then followed by the reaction with the nucleophile as shown in Scheme 43. 

Tetrazolium salts have found use as phase transfer catalysts in the oxidation of benzaldehyde640 and toluene193 and the displacement reaction of acid chlorides with sodium azide.639... 

With a common intermediate from the Medicinal Chemistry synthesis now in hand in enantiomerically upgraded form, optimization of the conversion to the amine was addressed, with particular emphasis on safety evaluation of the azide displacement step (Scheme 9.7). Hence, alcohol 6 was reacted with methanesul-fonyl chloride in the presence of triethylamine to afford a 95% yield of the desired mesylate as an oil. Displacement of the mesylate using sodium azide in DMF afforded azide 7 in around 85% assay yield. However, a major by-product of the reaction was found to be alkene 17, formed from an elimination pathway with concomitant formation of the hazardous hydrazoic acid. To evaluate this potential safety hazard for process scale-up, online FTIR was used to monitor the presence of hydrazoic acid in the head-space, confirming that this was indeed formed during the reaction [7]. It was also observed that the amount of hydrazoic acid in the headspace could be completely suppressed by the addition of an organic base such as diisopropylethylamine to the reaction, with the use of inorganic bases such as... 

The later publication [1] reveals that the title compound is in fact a relatively stable compound. The previously attempted preparation of the then unknown compound from trichloroacetonitrile, sodium azide and ammonium chloride (0.14 0.42 0.2 mol) by an analogous established method [2], but at lower initial temperature because of the exothermic reaction, gave, after vacuum evaporation of solvent, an oily product. When sampled with a pipette, this evolved gas and then exploded violently. It was thought that an azidomethyltetrazole may have been formed by displacement of chloro-substituent(s) by the excess azide employed [3], An alternative hypothesis which involved isomerisation of the title compound to the open chain azidoazomethine [4] was discounted, because no trace of this could be detected [1]. 

Reaction between 2,8-dichloro derivative 115 and sodium azide in DMSO does not lead to 3,9-diazido derivative 116 expected by direct displacement. Instead, the reaction gives isomeric 3,9-diazide 117, presumably by an addition-elimination sequence <1995JOC6110, 1995HAC391>. Compound 116 is available by treatment of tetra-nitro derivative 90 (z-TACOT) with LiN3 in DMSO (Scheme 11) <1967JA2626>. 

Azidodeoxy sugars are useful intermediates in the synthesis of aminodeoxy sugars. Nucleophilic-displacement reactions of sulfonate and deoxyhalo derivatives of sucrose with sodium azide have been used for the preparation of sucrose azides. The reaction of... 

The synthesis of inosamines from bromodeoxyinositols has been achieved by way of displacement reactions with sodium azide in boiling, aqueous 2-methoxyethanol or N,N-dimethylformamide.163... 

The synthesis of a triptan with a chiral side chain begins by reduction of the carboxylic acid in chiral 4-nitrophenylalanine (15-1). The two-step procedure involves conversion of the acid to its ester by the acid chloride by successive reaction with thionyl chloride and then methanol. Treatment of the ester with sodium borohy-dride then afford the alanilol (15-2). Reaction of this last intermediate with phosgene closes the ring to afford the oxazolidone (15-3) the nitro group is then reduced to the aniline (15-4). The newly obtained amine is then converted to the hydrazine (15-5). Reaction of this product with the acetal from 3-chloropropionaldehyde followed by treatment of the hydrazone with acid affords the indole (15-6). The terminal halogen on the side chain is then replaced by an amine by successive displacement by means of sodium azide followed by catalytic reduction of the azide. The newly formed amine is then methylated by reductive alkylation with formaldehyde in the presence of sodium cyanoborohydride to afford zolmitriptan (15-7) [15]. 

Nucleophilic displacement of the sulfonate groups in methyl 2,6,2, 3, 4 -penta-0-acetyl-3,6 -di-0-(methylsulfonyl)-/3-maltoside was readily achieved with sodium azide in hexamethylphosphoric triamide, to give methyl 3-azido-4-0-(6-azido-6-deoxy-a-D-gluco-pyranosyl)-3-deoxy-/3-D-allopyranoside pentaacetate.45 Catalytic hydrogenation of the 3,6 -diazide, followed by acetylation, gave the 3,6 -diacetamido derivative in high, overall yield. In a similar sequence of reactions, methyl 2,3,2, 3, 4 -penta-0-acetyl-6,6 -di-0-p-tolylsulfonyl-/3-maltoside has been transformed into the corresponding 6,6 -diac-etamido derivative.45... 

A one-pot PTC reaction procedure for the overall conversion of an alkyl halide into a primary amine via an azide is particularly illustrative.204 Thus the reduction of the azide is effected by the addition of sodium borohydride to a reaction mixture arising from the PTC displacement reaction of an alkyl halide with sodium azide (the preparation of 1-octylamine, Expt 5.193). The reaction appears to be applicable to primary and secondary alkyl halides, alkyl methane-sulphonates and benzylic halides. 

J. S. Brimacombe, J. Minshall, and L. C. N. Tucker, Nucleophilic displacement reactions in carbohydrates. 22. Formation of 1,4-anhydropyranoses from l-0-acetyl-6-deoxy-2,3-O-isopropylidene-4-O-methylsulphonyl-u-L-manno- and -talo-pyranose with sodium azide, J. Chem. Soc., Perkin Trans. 1, (1973) 2691-2694. 

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