Sodium azide, reaction with ketones

It is also possible to use amine surrogates in this type of reaction. When sodium azide reacted with the bromide moiety in 7.735 (see reaction 5), an a-azido-ketone was formed. This azide was reduced in situ to give ethyl 3-amino-4-oxopent-2-enoate, 1.136. ... 

The Schmidt reaction of ketones works best with aliphatic and alicyclic ketones alkyl aryl ketones and diaryl ketones are considerably less reactive. The reaction is only seldom applied to aldehydes as starting materials. The hydrazoic acid used as reagent is usually prepared in situ by treatment of sodium azide with sulfuric acid. Hydrazoic acid is highly toxic, and can detonate upon contact with hot laboratory equipment. 

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. 

Nitrilium salts, e.g., 66, prepared from the alkylation of nitriles, react with sodium azide to yield 1,5-disubstituted tetrazoles, e.g., 67 (Scheme 7).121 The Schmidt reaction,122 a versatile method for the preparation of 1,5-disubstituted tetrazoles from ketones and hydrazoic acid, can now be regarded as a special case of azide addition to nitrilium salts.123... 

Other approaches to tetrazoles were also recently published. Primary and secondary amines 195 were reacted with isothiocyanates to afford thioureas 196, which underwent mercury(II)-promoted attack of azide anion, to provide 5-aminotetrazoles 197 . A modified Ugi reaction of substituted methylisocyanoacetates 198, ketones, primary amines, and trimethylsilyldiazomethane afforded the one-pot solution phase preparation of fused tetrazole-ketopiperazines 200 via intermediate 199 <00TL8729>. Microwave-assisted preparation of aryl cyanides, prepared from aryl bromides 201, with sodium azide afforded aryl tetrazoles 202 . 

Acetylcarbazole and 9-ethyl-3-propionylcarbazole underwent normal Wilgerodt reactions. The ketone 174 reacted with sodium azide-poly-phosphoric acid with migration of the alkyl substituent generating lactam 203. ... 

The lactam (2) is obtained in 87% yield by treating cycloheptanone with sodium azide and concentrated hydrochloric acid (54JA2317). Beckmann rearrangement of cycloheptanone oxime with concentrated sulfuric acid gives (2) in 88% yield (58JA1510). Alternatively, the ketone gives (2) directly by reaction with hydroxylamine sulfonate in 95% formic acid (79S537). 

The intramolecular 1,3-dipolar cycloaddition reaction of azides has become an increasingly useful process for the construction of natural products and molecules of theoretical interest.192 193 For example, 2-substituted azido enone (238) was prepared from the corresponding bromide by treatment with sodium azide. Thermolysis of this material afforded aziridinyl ketone (240) presumably via a transient dipolar cycloadduct (239).193 Ketone (240) was subsequently converted to an intermediate previously used to prepare histrionicotoxin (241 Scheme 56). 

Recently Zbiral and Stroh reported that treatment of a-azido-ketones (obtained generally by reaction of the a-halogenoketone with sodium azide) with triphenylphosphine is a convenient route to 2,5-disubstituted pyrazines (Scheme 5). Thus, 2,5-diphenyl-, 2,5-bis(4-methoxyphenyl)-, and 2,5-diisopropylpyrazine have been obtained in 75, 45, and 44% yield, respectively. The intermediate P-iV-ylide undergoes intermolecular condensation to give a 2,5-dihydropyrazine which is subsequently aromatized.122... 

Thermal decomposition of 3-azido-2-formylfuran, -thiophene, and -selenoles has also been used to prepare furo[3,2-c]isoxazole (97), thieno[3,2-c]isoxazole (4), and selenolo[3,2-c]isoxazoles (98) (Equation (27)) <76CS165>. In contrast, some azido ketones eliminate nitrogen at ambient temperature and cyclize as exemplified in the reactions of 2-chloro-3-acetylindole (99) (Equation (28)) and 3-chloro-2-benzoylbenzothiophene dioxide (101) (Equation (29)) with sodium azide (78CB1521, 92JOC2127). 

The reaction of sodium azide with l-bromo-l-nitro-2-arylethenes takes place by a formal 1,3-cycloaddition Scheme leading to 4(5)-aryl-5(4)-nitro-l,2,3-triazoles [487-489], During the synthesis of nitrotriazoles the bromonitroarylethenes can be replaced successfully by the more readily obtainable l,2-dibromo-l-nitro-2-arylethanes [489], The intermediate product in the synthesis of 3-nitropyrazoles from 2,2-dinitroethanol and diazo ketones or diazoacetic ester is 1,1-dinitroethene [490,491] (Scheme 68). 

The reaction of alkenes with iodosobenzene in acetic acid in the presence of sodium azide offers a simple and high yield route to 1,2-diazides (Table 3)76. a-Azido ketones are side products or the exclusive product from the reaction with conjugated alkenes. Allylic azides or oxonitriles, resulting from oxidative cleavage of the C-C double bond, are alternatively obtained from trisubstituted steroid alkenes77. 

The reaction of equimolar quantities of hydrazoic acid with an acid or ketone affords a convenient method for preparing certain amines. The reaction is carried out by treating the organic compound in an inert solvent in the presence of sulfuric acid with gaseous hydrogen azide, hydrazoic acid in solution, or sodium azide directly. An excess of hydrazoic acid should be avoided in the reaction of ketones, for then tetrazoles are formed. It should be recalled that hydrazoic acid is toxic and explosive. A discussion of the method including scope and limitations, experimental conditions and procedures, and compounds prepared thereby has been presented. ... 

Azides are generally stable in the presence of bases and nucleophilic displacement of the azido group is uncommon, but displacements have been observed on a few vinyl azides. Reaction of j8-azidovinyl phenyl ketone 73 (R = H) with piperidine gave phenyl -2-piperidino-vinyl ketone (119) and reaction of the same azide with sodium hydroxide in aqueous methanol gave the dimethyl acetal 120 . 

Similarly, the 2-azidoethylene-l,l-dicarbonitriles (92) were found to react with aniline to give the corresponding anilino derivatives 121 Reaction of phenyl ethynyl ketone with sodium azide in an aqueous medium, it will be recalled, gave the isoxazole 74 (R = H). When this reaction was carried out in dimethylformamide, quite different results were found in this case the sodium salt of 4-benzoyl-1,2,3-triazole was isolated in good yield . The formation of this product... 

This azide, prepared by adding a solution of n-butyl bromide to a slurry of of sodium azide in water, cleaves ketones of the type ArCOCHjR in benzene or nitrobenzene at 70-90° in the presence of a catalytic amount of sulfuric acid to two carbonyl components. Acetophenone gives benzaldehyde (80%) and formaldehyde (83%) propiophenone gives benzaldehyde and acetaldehyde. The reaction is interpreted as involving combination of the azide with the coiyugate acid of the ketone, release of nitrogen from the diazonium cation with elimination of water, hydration, and cleavage. 

Preparation. By reaction of picryl chloride with sodium azide or by nitration of o- or p-nitroazidobenzene. Like cyanogen azide which see), the reagent (1) reacts with an olefin either to form a Schiff base (2), convertible into the corresponding ketone (3), or to form an aziridine (4). Simple olefins give Schiff bases. The reagent is much safer to handle than cyanogen azide. 

For some of the simple 4,5-dihydro-3//-pyrazoles not available by the diazoalkane-alkene route, an alternative to the hydrazine reaction discussed in the last section is oxidative cyclization of a 1,3-diamine. Hence, an alternative preparation of the ketone 1 is to react 2,4-dibromo-2,4-dimethylpentan-3-one with sodium azide, reduce the azide groups with ammonium polysul-fide " and oxidatively cyclize with sodium hypobromite. " ... 

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