Alkyl azides preparation

Alkyl azides prepared by nucleophilic substitution of alkyl halides by sodium azide as shown m the first entry of Table 22 3 are reduced to alkylammes by a variety of reagents including lithium aluminum hydride... 

Alkyl azides prepared by nucleophilic substitution by azide ion in primary or secondary alkyl halides are reduced to primary alkylamines by lithium aluminum hydride or by catalytic hydrogenation... 

The Cunius degradation of acyl azides prepared either by treatment of acyl halides with sodium azide or trimethylsilyl azide [47] or by treatment of acyl hydrazides with nitrous acid [f J yields pnmarily alkyl isocyanates, which can be isolated when the reaction is earned out in aptotic solvents If alcohols are used as solvents, urethanes are formed Hydrolysis of the isocyanates and the urethanes yields primary amines. 

A better method for preparing primary amines is to use the azide synthesis, in which azjde ion, N3, is used for SN2 reaction with a primary or secondary alkyl halide to give an alkyl azide, RN3. Because alkyl azides are not nucleophilic, overalkylation can t occur. Subsequent reduction of the alkyl azide, either by catalytic hydrogenation over a palladium catalyst or by reaction with LiAlK4. then leads to the desired primary amine. Although the method works well, low-molecular-weight alkyl azides are explosive and must be handled carefully. 

CAUTION All azides, particularly low molecular weight acyl and alkyl azides, are explosive, and great care should be taken while preparing and handling these materials. In addition, hydrazoic acid, which is liberated from unbuffered aqueous solutions of sodium azide, is highly toxic and all operations involving its use should be carried out in an efficient fume hood. 

Alkyl azides can be prepared by treatment of the appropriate halide with azide ion. ° Phase-transfer catalysis,ultrasound,and using reactive clays as a... 

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... 

We have recently developed a general method of preparation of the heretofore relatively unknown trialkyltriazenes ( ). These substances are readily prepared by reaction of a Grignard reagent or an alkyllithium with an alkyl azide, followed by the reaction of the Intermediate dlalkyltrlazene with base, and alkylation of the resulting trlazenyl anion with an alkyl halide. 

There are also useful procedures for preparation of azides directly from alcohols. Reaction of alcohols with 2-fluoro-l-methylpyridinium iodide followed by reaction with lithium azide gives good yields of alkyl azides.75... 

In an investigation of the intramolecular Schmidt reaction of alkyl azides for the synthesis of benzo-fused l-azabicyclo[m.n.O]alkanes, the perhydrobenzo[/]pyrrolo[l,2-a] azepine 29 was prepared in 72% yield . 

Relatively few additions of the lower molecular weight alkyl azides have been performed, mainly because of their volatility and thermal sensitivity simple alkyltriazoles are normally obtained by alkylation of the w-triazoles. On the other hand, a very wide range of less volatile substituted alkyl azides has been added to acetylenes Their addition to acetylenic esters usually proceeds readily and provides a useful method of characterizing the azides. Benzyl azide has often been used because it is relatively stable (up to 150°), it is readily prepared, and the benzyl group can be removed from the resulting triazoles (Section IV, E). 

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. ... 

The method of preparation and physical properties of the alkyl azides used in the study are also presented in Table 2.1. The alkyl bromide and sodium azide in aq MeOH is denoted as A and aq EtOH and sodium azide is denoted as B. 1,2-Diazidobenzene and 1,4-diazidobenzene were synthesized using the process shown in Fig. 2.10. 1-Azidonorborniane was synthesized according to a modified literature procedure shown in Fig. 2.11. 

L abbe and co-workers have found that 4-alkyl-5-sulfonylimino-A -l,2,3,4-thiatriazolines (58) are readily prepared by reaction of the highly reactive sulfonyl isothiocyanates with alkyl azides (Equation (19)) <73JOC2916, 74JA3973). 

This method is superior to the reaction of NHj and RX for the preparation of RNHj because no polyalkylation occurs. However, alkyl azides are explosive and must be carefully handled. Rather than being isolated, they should be kept in solution and used as soon as made. 

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. 

An improved method of preparing alkyl azides has been reported wherein Carbitols are used as solvents for the interaction of an alkyl halide and commercial sodium azide [10]. The use of activated sodium azide [34] is not necessary. Sealed-tube reactions for alkyl azides are hazardous a violent explosion has been reported in an attempt to seal such a tube [35]. No reactions reported in this chapter involve sealed tubes. Table II describes the conditions and azides prepared using the Carbitol solvents. 

Preparation of Alkyl Azides from Sodium Azide, Alkyl Iodides, or Bromides, and Carbitol Solvents at 95°C for 24 hr... 

Ahad, E. (1990) Process for the preparation of alkyl azide substituted hydroxy terminated polyethers. US Patent 4,891,438 Chem. Ahstr., (1988) 109,171140u. 

Alkyl azides can be prepared by treatment of the appropriate halide with azide ion.939 Phase transfer catalysis940 and ultrasound941 have been used. Other leaving groups have also been used,942 for example, OH,943 OMs, OTs,944 and OAc.945 Epoxides react with NaN3, with HN3 in DMF,94 or with HN3-Et3Al947 to give 3-azido alcohols these are easily converted to aziridines,948 e.g.,... 

When the more reactive sulfonyl isothiocyanates are used as 1,3-dipolarophiles 4-alkyl-5-sulfonylimino-A2-l,2,3,4-thiatriazolines are readily prepared at room temperature by reaction with alkyl azides.64,65 The thiatriazolines are obtained in 50-75% yield. Their structures are deduced from NMR, IR, and mass spectral data and degradation experiments. Thus thermal decomposition at moderate temperature (45°-80°) in inert solvents (dry toluene, CC14, acetone) furnished the corresponding carbodiimides [Eq. (22)]. These were identified by their... 

Alkyl azides. Sodium azide as such is of little use for preparation of alkyl azides by nucleophilic substitution reactions because of solubility problems. The reaction can be carried out under phase-transfer conditions with methyltrioctylam-monium chloride/NaN3.3 An even more effective polymeric reagent can be obtained by reaction of NaN3 with Amberlite IR-400.4 This reagent converts alkyl bromides, iodides, or tosylates into azides at 20° in essentially quantitative yield. The solvents of choice are CH3CN, CHC13, ether, or DMF. 

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