Azides, from alkyl halides

Preparation of alkyl azides The azide ion (N3 ), a good nucleophile, can displace leaving groups from 1° and 2° alkyl halides. Alkyl azides are easily prepared from sodium or potassium azides and alkyl halides. The reaction mechanism resemhles the formation of nitrile. 

Primary amines can be prepared from alkyl halides by 0-44, by 0-63, by 0-61 followed by reduction of the azide (9-53), or by the Gabriel synthesis (0-58). 

As these compounds all possess a nitrogen-containing functional feature, it is worth pointing out that they arise from alkyl halides (or methanesulphonates) in the case of azides and cyanides, or from carboxylic acid chlorides (in the case of amides). 

The limitations of this approach can be seen in the reaction of a saturated solution of ammonia in 90% ethanol with ethyl bromide in a 16 1 molar ratio, under which conditions the yield of primary amine was 34.2% (at a 1 1 ratio the yield was 11.3%). Alkyl amines can be one type of substrate that does give reasonable yields of primary amine (provided a large excess of NH3 is used) are a-halo acids, which are converted to amino acids. A-Chloromethyl lactams also react with amines to give good yields to the A-aminomethyl lactam. Primary amines can be prepared from alkyl halides by 10-43, followed by reduction of the azide (19-32), or by the Gabriel synthesis (10-41). 

The yield of a 1-adamantamine decreases in the presence of a more polar compound, such as cyclohexanol, which adsorbs more readily onto TiOj particles than 1-azidoadamantane. Because azides can be produced readily from alkyl halides, photoreduction of azides on SC provides an easier alternative to amine synthesis [151]. 

Several heterogeneous catalysts have been shown to effect related multicomponent couplings. These include cross-linked polymeric ionic liquid material-supported copper (Cu-CPSIL), silica-dispersed CuO (CuO/Si02), and imidazolium-loaded Merrifield resin-supported copper (Cu-PSIL), all of which can be used in water at room temperature to arrive at 1,4-disubstituted-1,2,3-triazoles from alkyl halides, NaNs, and terminal alkynes. Each can be filtered and reused several times with minimal loss of efficacy. Multistep flow synthesis, specifically including generation of underused vinyl azides and their subsequent click conversions to vinyl triazoles, has also been reported. ... 

Unfortunately, these reactions don t stop cleanly after a single alkylation has occurred. Because ammonia and primary amines have similar reactivity, the initially formed monoalkylated substance often undergoes further reaction to yield a mixture of mono-, di-, and trialkylated products. A better method for preparing primary amines from alkyl halides is to use azide ion, N3, as the nucleophile rather than ammonia. The product is an alkyl azide, which is not nucleophilic, so overalkylation can t occur. Subsequent reduction of the alkyl azide with LiAlH4 then leads to the desired primary amine. 

Triazoks were synthesized from simple starting materials without the need for additional catalyst. Organic azides, generated in situ from alkyl halides and sodium azide, were reacted with acetylenes using the copper-catalyzed Huisgen 1,3-dipolar cydoaddition. 

Typical conditions for these processes are simply to stir an aqueous solution of the metal salt of Y with the organic substrate alone, or in a solvent such as chloroform or benzene, in the presence of 5—10 mole % of a quaternary ammonium salt as catalyst. A recent example is to be found in a synthesis of alkyl azides from alkyl iodides (or other halides) using commercially available Aliquat 336 [mainly (1)] as catalyst, and a reaction temperature of 100 °C. The conversion of alkyl methanesulphonates to alkyl halides has been used to synthesize optically active secondary fluorides, chlorides and bromides via an 5 n2 inversion mechanism (the iodides racemize before isolation). Ammonium salt (1), or phosphonium salt (2), are used to catalyse these mesylate displacements. ... 

Tertiary alkyl azides can be prepared by stirring tertiary alkyl chlorides with NaN3 and ZnCl2 in 82 ° or by treating tertiary alcohols with NaN3 and CF3-COOH or with HN3 andTiCl4 or BF3. Acyl azides, which can be used in the Curtius reaction (18-14), can be similarly prepared from acyl halides, anhydrides, " esters, or other acyl derivatives. ° Acyl azides can also be prepared... 

Mg or Ca in MeOH, " baker s yeast, Sm/l2, LiMe2NBH3, and tin complexes prepared from SnCl2 or Sn(SR)2. This reaction, combined with RX —+ RN3 (10-65), is an important way of converting alkyl halides RX to primary amines RNH2 in some cases the two procedures have been combined into one laboratory step. Sulfonyl azides (RSO2N3) have been reduced to sulfonamides (RSO2NH2) by irradiation in isopropyl alcohol and with NaH. ... 

Alkyl azides are conveniently prepared from the reaction of alkali metal azides with an alkyl halide, tosylate, mesylate, nitrate ester or any other alkyl derivative containing a good leaving group. Reactions usually work well for primary and secondary alkyl substrates and are best conducted in polar aprotic solvents like DMF and DMSO. The synthesis and chemistry of azido compounds is the subject of a functional group series. ... 

Alkyl and aryl azides are prepared by the nucleophilic displacement by azide ion on halide, sulfate, phenyldiazonium, hydroxyl, nitrate, iodoxy, alkoxy, and tosylate groups [6]. Sodium azide is the most useful and practical reagent. The use of silver azide is not necessary in most cases. Some examples from the literature [8-33] employing these methods are shown in Table I. 

Organic azides can be prepared from hydrazines and nitrous acid (Section 24-7A) and by the reaction of sodium azide with acyl halides or with alkyl halides having good SN2 reactivity ... 

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