Hazardous azides

The authors have also elaborated a microwave-enhanced one-pot procedure [90] for the Huisgen 1,3-dipolar cycloaddition reaction. In a typical procedure, a pyrazinone with a triple bond connected to the core via C - O linkage, was reacted with a suitable benzylic bromide and NaNs in presence of the Cu(I) catalyst in a t Bu0H/H20 system under microwave irradiation (Scheme 26). The cycloaddition was found to proceed cleanly and with full regioselectivity. As the azide is generated in situ, this procedure avoids the isolation and purification of hazardous azides, which is especially important when handling the ahphatic ones, which are known to be toxic and explosive in nature. 

However, the two syntheses of Tamiflu, involving two potentially hazardous azide-containing intermediates, need further improvements. A recently published short and enantioselective pathway starting from acrylic acid and 1,3-butadiene looks promising [47]. 

Chapter 2 of this volume discusses the chemical characterization, basic techniques found useful, and the problems of analysis for hazardous azides in complex media. The data presented constitute a foundation upon which much of the information presented in the other chapters must stand, and the more refined techniques described are also critical to the success of much of the fundamental research described in Volume 1. The importance can perhaps best be crystallized in the statement that unless the species profiles of samples are known, data on other properties cannot be safely ascribed to any particular substance. 

Further phenylation can be accomplished by reaction with phenylmagnesium bromide to give products only previously obtained by the potentially hazardous azide route. Sulphamic acid also reacts with phenylchlorophosphoranes in a similar way ... 

To avoid the direct manipulation with hazardous azides, methods using Cu(I)situ generation of azides were developed as one-pot procedures, for example, with substitution reaction of alkyl hahdes by NaN3 [493] or with nitrosation of aromatic primary amines by tBuONO followed by trimethylsilyl azide [494]. Vice versa, the alkyne component has been generated in situ, for example, by sequential Seyferth-Gilbert reaction (homologation of aldehydes with diazophosphonates) and reaction with azides in a Cu(l)-catalyzed cycloaddition [495]. 

Keep hazardous azides in solution as long as possible. Solvents desensitize explosives by reducing the sensitivity to mechanical stress. 

Copper-catalyzed azide-alkyne cycloaddition (CuAAC) has been widely used in the post-glycosylation of pre-formed polymers, for which the protected aUcyne monomers can be first polymerized by various LRP strategies followed by removal of trimethylsilyl (TMS) protection groups using tetrabutylammonium fluoride (TBAF)/ acetic acid for click reaction with azido functional sugars (Fig. 3) [59, 60]. This approach avoids the use of hazardous azide-functionalized monomers and utilizes the diversity of well-documented azido functional sugars [59]. 

A much greater yield can be had if the chemist uses carbitol as a solvent instead of propanol [62]. Carbitol is a really hazardous solvent and should not be breathed or placed on one s skin. The reaction proceeds exactly as before except that after 24 hours of reflux and cooling the mixture is slowly poured into 1500mL ice cold dH20. The upper solvent layer is separated and the aqueous layer extracted with 200mL ether which is then combined with that upper solvent layer. The combined solvent portions are vacuum distilled to afford safrole-azide (or phenylisopropyi-azide for amphetamine) with the yield rising to 70%. 

I. Kabek and S. Urman, "Hazards of Copper Azide ia Fuzes," ia Minutes of the 14th Annual Explosives Safety Seminar, NTIS, 1972, p. 533. 

Many investigations are reported on azides of barium, calcium, strontium, lead, copper, and silver in the range 100 to 200°C (212 to 392°F). Time exponents were 6 to 8 and activation energies of 30 to 50 kcal/g mol (54,000 to 90,000 Btu/lb mol) or so. Some difficulties with reproducibility were encountered with these hazardous materials. 

Salts. In addition to the dangers of perchlorate salts, other salts such as nitrates, azides and diazo salts can be hazardous and due care should be taken when these are dried. Large quantities should never be prepared or stored for long periods. 

Other reagents which have been found useful for the sjmthesis of t-BOC derivatives include the hazardous tert-butoxycarbonyl azide ... 

Caution/ Although the organic azide intermediates used in this procedure ham not shown any explosive hazard under the experimental conditions. 

Although several interesting nitrogen-centered nucleophiles have been developed with ARO reactions of epoxides (vide supra), kinetic resolutions with such reagents are unlikely to be of practical value for the recovery of enantioenriched terminal epoxides. This is due to the fact that these nucleophiles are too valuable to be discarded in a by-product of the resolution, are generally not atom-economical, and, particularly in the case of azide, may represent safety hazards. 

The reaction of Lead Azide (LA) with Cu (see Table) deserves special comment, Although this reaction is relatively slow, even in the presence of w, some forms of Cu Azide are so sensitive that they create a serious hazard even in minute quantities, particularly when in contact with LA. For this reason, AJ and stainless steel containers are now used exclusively. PicArsn requires that all new fuze designs contain no Cu or Cu alloys, with the possible exception of the electrical system. Even here, the Cu must be coated for protection against the formation of hydrazoic acid. Another prohibition involves the use of Pb thiocyante in contact with A1 (Refs 4, 5 6)... 

It is difficult to obtain accurate particle size analyses of primary expls because (1) consideration and acceptance of necessary safety precautions make the usually tedious job of particle size analysis even more tedious, and (2) many primary expls used in production contain particles which are non-spherical in shape and are in the subsieve size range. Dry screening Lead Azide, for instance, is hazardous and must be done remotely. Furthermore, static charges... 

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... 

Two crystallographic forms of lead azide are important, the ordinary alpha form which is orthorhombic and the beta form which is monoclinic. The densities of these forms are 4-71 and 4-93 respectively. It was for many years believed that the beta form is the more sensitive to friction and impact and accounted for detonations which have occurred in the manufacture and handling of the substance. It is now known that the beta form is in fact no more sensitive than the alpha. Even the alpha form, when present as large crystals, is very sensitive and conditions can arise (particularly when the formation of the lead azide is controlled by diffusion effects) where spontaneous detonation occurs. Although with modern knowledge these hazards can be avoided, pure lead azide is nevertheless a dangerous compound and is now made only for military purposes. 

The solid explodes when mechanically shocked or heated in a closed vessel [1], Preparative methods are hazardous because of the need to heat the explosive precursor, cyanogen azide [1,2]. 

Preparative hazard See 2,4,6-Triazido-l,3,5-triazine See other ORGANIC AZIDES... 

Perchlorate salts of the azide complexes, and also of the dichloro analogue, may present an explosion hazard. 

A solution, prepared by mixing saturated solutions of cadmium sulfate and sodium azide in a 10 ml glass tube, exploded violently several horns after preparation [1], The dry solid is extremely hazardous, exploding on heating or light friction. A violent explosion occurred with cadmium rods in contact with aqueous hydrogen azide [2], A DTA study showed a lesser thermal stability than lead azide [3], It is strongly endothermic (AH°f (s) +451 kJ/mol, 2.32 kJ/g). 

A new method of preparation from vanadium nitride and chlorine [1] is free of the explosion hazards of chlorine azide and vanadium azide tetrachloride present in an earlier method [2],... 

It is a tribute to Leslie that very little of the new information in the 5th and this edition is old stuff that he missed almost all comes from new publications. The entries on new groups range from acrylates to yeast passing through drums, fumes, mists and pnictides on the way. Familiar accidents continue to occur and new entries have been added on well-known hazards, such as nitric acid and azides. 

The products are isolated in good yield in a one-stage synthesis from starting materials that are readily available in the main. An alternative method involves the decomposition of the corresponding azides.9,12 These compounds are less readily available and are more hazardous to use than are the nitro compounds used in the present synthesis. This synthesis also gives better yields than the cyclization using ferrous oxalate, 2,13 which is performed under much harsher conditions. 

Numbers 7 and 8 in Table 3.6 represent high hazard substances such as azides, peroxides, perchlorates, and nitro compounds. The handling of such materials requires extreme care and safety precautions. 

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