Reactions with hydrazoic acid

A1( -octalone, 45, 80 N-nitioso-N-phenylglycine to N-phenylsydnone, 45, 96 Cyclobutanecarboxylic acid, reaction with hydrazoic acid, 47, 28 Cyclobutene, 1,2,3,4-tetrasiethyl-3,-4-dichloro-, 46, 34 reactions of, 46, 36 Cyclobutylamine, 47, 28 Cyclobutyl isocyanide, 46, 77 Cycloheptanone, 45, 31... 

The most general reaction for the preparation of sulphoximines from sulphoxides is simply by reaction with hydrazoic acid (equation 65)178. Highly substituted sulphoxides, such as diethyl sulphoxide with more than two chlorine substituents, do not undergo reaction to form the sulphoximine in this way. 

The mechanism is similar to those of the analogous reactions with hydrazoic acid (18-16 with ketones) and diazomethane (18-8) ... 

Carboxylic acids and esters can also be converted to amines with loss of the carbonyl group by reaction with hydrazoic acid, HN3, which is known as the Schmidt reaction,278 The mechanism is related to that of the Curtius reaction. An azido intermediate is generated by addition of hydrazoic acid to the carbonyl group. The migrating group retains its stereochemical configuration. 

The reaction with hydrazoic acid converts ketones to amides. 

Quinoneimides add hydrazoic acid in a similar manner to quinones . The equilibrium in the amide-imide prototropic shift is more one-sided than that of the keto-enol system and thus, even in the naphthalene series, reaction with hydrazoic acid affords an azide (equation 83). 

The pattern of addition in polyenes in which the double bonds are neither contiguous nor conjugated does not require special comment. Compounds with conjugated double bonds are somewhat more susceptible to electrophilic addition than simple alkenes but nevertheless there appear to be no literature reports of such compounds undergoing addition reactions with hydrazoic acid in the absence of a catalyst. 

Depazay and co-workers have described the synthesis of a series of polyhydroxylated pyrrolidine, piperidine and azepanes derived from D-mannitol as novel mimetics of somatostatin [8]. The synthesis of one piperidine 116 is shown in O Scheme 9. The authors used reaction of tr) tamine with the D-mannitol derived bis-epoxide 112 followed by protection of the indole nitrogen with a Boc group to prepare the L-gulo-piperidine 113, the azepane 114 also being formed. Selective protection of the primary alcohol followed by reaction with hydrazoic acid... 

Schmidt reaction (see review ). This reaction provides a method for the conversion of a carboxylic acid into an amine in one step. On reaction with hydrazoic acid in benzene in the presence of sulfuric acid, an acid is converted beyond the stage of the acyl azide (a) into the conjugate acid (b), which loses nitrogen more easily than the azide itself, with rearrangement to the isocyanate (d). The one-step... 

An aryl cyclopropyl ketone reacted with hydroxylamine followed by a mixture of tosyl chloride and pyridine to give the corresponding 7V-arylcyclopropanecarboxamide as the sole product in fair yield.Alkyl cyclopropyl ketones, on the other hand, afforded mixtures of the corresponding A-alkylcyclopropanecarboxamide and A7-cyclopropylalkanamide in excellent total yield on reaction with hydrazoic acid (Schmidt reaction) in the presence of sulfuric acid or trichloroacetic acid, an example is the formation of 3. When sulfuric acid was used, the amide ratio was sensitive to the acid strength of the reaction mixture. ... 

Carboxylic acids and esters can also be converted to amines with loss of the carbonyl group by reaction with hydrazoic acid, HN3. This is known as the Schmidt... 

When the Schmidt reaction is applied to a,j8-unsaturated carboxylic acids, the product of the rearrangement is an enamine, which hydrolyzes to the corresponding ketone. Entry 3 in Scheme 8.9 is an example of this type of reaction. Reaction with hydrazoic acid converts ketones to amides, and is thus an alternative method for effecting the same transformation as the Beckmann rearrangement. A drawback of... 

Finally, the Eschenmoser-Claisen rearrangement has found appUcations in drug synthesis. Mulzer s synthesis of the antidepressant (J )-rolipram serves as an example (Scheme 7.36) [84]. Rearrangement of chiral cinnamyl alcohol 104 gave unsaturated amide 105 with Uttle erosion of optical purity. Ozonolysis and reduction afforded alcohol 106 and set the stage for a subsequent Mitsunobu reaction with hydrazoic acid. Reduction of the azide function followed by intramolecular transamidation gave y-lactam 107, which was converted into (R)-rolipram in two straightforward steps. 

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