Hydrazoic acid with alcohols

Curtius and Rissom [41] prepared cupric azide by the action of an aqueous solution of sodium azide on an aqueous solution of cupric sulphate, obtaining the salt in a hydrated form. The anhydrous salt was prepared by Straumanis and Ciru-lis [125] in the form of dark brown, reddish sediment by reaction of lithium azide on cupric nitrate in an alcohol solution. Another method described by Curtius consists of reacting hydrazoic acid with metallic copper in an aqueous medium. 

Lead azide, which is normally stored in alcohol-water, reacts with the liberation of hydrazoic acid. It is possible to detect hydrazoic acid in the vapors over lead azide immersed in alcohol-water. With other azides, such as that of barium, water can generate hydrazoic acid readily. The normal laboratory preparation of hydrazoic acid is to acidify sodium azide and distill the hydrazoic acid with an inert gas carrier. The explosion limits of this substance have not been established with any degree of assurance however, it is known that hot spots and sparks will initiate gaseous mixtures of hydrazoic acid in air [1,2]. 

Lead azide is also obtainable from lead nitrite and hydrazoic acid [295]. Unlike simple metathesis, nitrite and azide react chemically to yield two inert gases, N2 and N2O, besides water, and the precipitated lead azide is, therefore, free of any coprecipitated ions. In practice, lead nitrite is first made by bubbling N2O3 into a suspension of lead oxide in water, and the yellow solution is then reacted with hydrazoic acid as alcoholic solution, or as gas carried with nitrogen ... 

The Schmidt reactions refer to the acid-catalyzed reactions of hydrazoic acid with electrophiles, such as carbonyl compounds, tertiary alcohols and aUcenes. These substrates undergo rearrangement and extrusion of nitrogen to furnish amines, nitriles, amides or imines. 

In the formation of tert-butyl azidoformate by the addition of phosgene to alcohols followed by the addition of Na nitride or hydrazoic acid in the presence of pyridine, reaction of phosgene with the azide can cause the formation of expl carbazide (Ref 9)... 

There are actually three reactions called by the name Schmidt reaction, involving the addition of hydrazoic acid to carboxylic acids, aldehydes and ketones, and alcohols and alkenes. The most common is the reaction with carboxylic acids, illustrated above.Sulfuric acid is the most common catalyst, but Lewis acids have also been used. Good results are obtained for aliphatic R, especially for long chains. When R is aryl, the yields are variable, being best for sterically hindered compounds like mesi-toic acid. This method has the advantage over 18-13 and 18-14 that it is just one laboratory step from the acid to the amine, but conditions are more drastic. Under the acid conditions employed, the isocyanate is virtually never isolated. 

Diphenylphosphoryl azide reacts with alcohols in the presence of triphenylphosphine and DEAD.76 Hydrazoic acid, HN3, can also serve as the azide ion source under these conditions.77 These reactions are examples of the Mitsunobu reaction. 

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... 

A one-pot procedure for the conversion of alcohols into alkylamines is by treatment of the former with hydrazoic acid in the presence of triphenylphosphine and diisopropyl azodicarboxylate addition of triphenylphosphine to the resulting azide gives an hninophosphorane, which is hydrolysed to the alkylamine by water (equation 8)35. 

Tertiary alcohols or halides react with hydrazoic acid in sulfuric acid to give imines. Under the same conditions, benzhydrol gives A-benzylidene-aniline in 90 % yield [52]. 

In the first stage of the reaction an alkoxyl anion and the nitrohydrazine cation are formed which afterwards react together to give the corresponding alcohol and nitrohydrazine. Nitrohydrazine reacts with excess hydrazine to produce tetrazene, nitrous acid and di-imid. Then the tetrazene decomposes to form ammonia and nitrogen from di-imid on the other hand tetrazene, hydrazine and nitrogen are formed. Hydrazoic acid and ammonia are then formed as decomposition products of tetrazene. 

The testosterone ester derivative (10 mmol) is dissolved in ca. 100 ml of a solution of hydrazoic acid in chloroform (0.15 M)138 and treated with stirring with a solution of 20 ml of f-butyl alcohol and N-chlorosuccinimide (2 g, 15 mmol). The reaction mixture is stirred for 8-10 hr and then added with stirring to a saturated solution of sodium bisulfite. The mixture is diluted with 200 ml of chloroform and washed with water. The chloroform layer is further washed with dilute sodium bicarbonate solution and water, dried (Na2S04) and the solvent removed in vacuo. The residual /-butyl alcohol is removed by repeatedly adding methanol to the product and concentrating to dryness in vacuo. The residue is triturated four times with Skellysolve F to separate the two isomeric adducts, (103) and (104). 

To prevent waste, the receiver should be followed by a flask containing methyl alcohol, and fitted with a calcium chloride tube. The apparatus should be placed in a hood behind a screen of thick plate-glass because anhydrous hydrazoic acid is very liable to explode violently at room temp. The hands should be protected by heavy gloves, and the face by a mask with plate-glass goggles. For phosphorus pentoxide as a desiccating agent, vide infra. 

T. Curtius and A. Darapsky prepared a basic salt, lanthanum hydroxyazide, La(0H)(N3)2l H20, by boiling a soln. of lanthanum nitrate and sodium azide. The white, slimy mass of basic lanthanum azide is obtained by evaporating the mixed soln. in vacuo, or by treatment of the soln. with a mixture of alcohol and ether. They also made rose-coloured didymium hydroxyazide, Dy(OH)(N3)2, by evaporating a soln. of didymium carbonate in hydrazoic acid. Freshly precipitated yttrium hydroxide dissolves in hydrazoic acid, forming a soluble yttrium hydroxyazide boiling a soln. of yttrium sulphate and sodium azide gives a precipitate of yttrium hydroxide. L. M. Dennis found that zirconium hydroxide is precipitated when a soln. of zirconium salt is treated with potassium azide. 

A 3 per cent solution of hydrazoic acid (synthesis 26A) is neutralized with an aqueous solution of pure potassium hydroxide. The resulting solution of potassium azide is concentrated on the steam bath to incipient crystallization. The solution is then made slightly acid with hydrazoic acid to replace the hydrogen azide lost by hydrolysis. A volume of ethyl alcohol twice that of the solution is added, and the solution is cooled in an ice bath. Since the solubility in alcohol of the alkali and alkaline earth azides is very slight (see table below), precipitation in the form of a white microcrystalline salt takes place readily. From 90 to 95 per cent recovery of the theoretical quantity of potassium azide can be effected. The precipitated azide is filtered on a Buchner funnel and washed with cold absolute alcohol and then with ether. Any traces of adhering solvent may be removed in a vacuum desiccator. In a typical run, 300 ml. of a solution of hydrazoic acid containing 8.5 g. of HN3 was neutralized with potassium hydroxide, and the isolation of potassium azide effected as indicated above. Yield 14.7 g. (91.5 per cent) KN3. 

The tetrazole analogue (341) of 7-oxocholest-5-en-3/3-yl acetate has been prepared 82 by reaction of the afi-unsaturated ketone with hydrazoic acid and boron trifluoride etherate hydrolysis of the 3)3-acetate and oxidation of the resultant alcohol furnished 7a-aza-B-homocholest-4-eno[7a,7-d]tetrazol-3-one. Cycloaddition of ethylenediamine to 2a-bromo-5a-cholestan-3-one has furnished a simple one-step route to 5 -cholestane[2,3-e]dihydro-2,3-pyrazine (342).183 Analogous cycloaddition has been achieved using 16a-bromoandrostan-17-ones. 

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