Nitrogen Schmidt rearrangement

Our consideration of rearrangements to electron-deficient heteroatoms must be brief. In discussing migrations to electron-deficient nitrogen, we first discuss three rearrangements that occur in carbonyl derivatives, the Beckmann, Hofmann, and Schmidt rearrangements, and then consider rearrangements of nitrenium ions. 

In the Schmidt rearrangement of carboxylic acids the formation of the adduct is apparently usually not rate-determining. The evidence for this comes from studies of the comparative rate of nitrogen evolution from HN3 in the presence and in the absence of carboxylic acids When m- or />-nitrobenzoic acid is added to HN3 in H2S04, the rate of nitrogen evolution decreases. Thus HN3 must be rapidly converted to an adduct from which loss of nitrogen is slower than from HN3 itself. Moreover, the adduct, to be formed at all, must be formed more rapidly than N2 is lost from HN3.165... 

Fluorenone oxime was recovered unchanged after being heated with PPA at 120°, but at 180° it was rearranged in almost quantitative yield (Conley )- Conley found PPA to be a superior solvent-catalyst for the Schmidt rearrangement. He added sodium azide in portions to a mixture of a diaryl, aryl-alkyl, symmetrical or unsymmetrical ketones with 15-20 parts of PPA at a temperature in the range 25-75° until evolution of nitrogen ceased, and obtained amides in yields mainly of 80-90%. Doorenbos and Wu studied the conversion of cholestanone and... 

The addition of hydrazoic acid onto non-activated olefins is a difficult reaction that has been observed only in rare cases. The main problem was the prevention of subsequent decomposition of the azide formed via nitrogen release or Schmidt rearrangement due to harsh reaction conditions that are typically employed. 

The Schmidt reaction of ketones with hydrazoic acid is believed to be a similar rearrangement, again with concerted trans migration and elimination of nitrogen. 

Reactions which insert an O or NH group next to a carbonyl can be used to form heterocycles (Scheme 23). The Schmidt reaction or the Beckmann rearrangement can accomplish this for nitrogen, the Baeyer-Villiger oxidation does it for oxygen. For example, cyclohexanone is converted in this way into 2-azepinone and into 2-oxepinone cycloheptanone yields the corresponding eight-membered heterocycles. 

This reaction is related to the Hofmann and Schmidt Reactions and the Curtius Rearrangement, in that an electropositive nitrogen is formed that initiates an alkyl migration. 

The most important nitrogen insertion reactions are still the Schmidt and the Beckmann rearrangements and their modifications. Yet, a number of other nitrogen insertion reactions are known, and examples will be therefore given and discussed. 

Other Nitrogen-containing Derivatives of Ketones.—The Schmidt reaction of 6- and 7-oxo-steroids (with NaNj-polyphosphoric acid) gave the same lactams as the Beckmann rearrangements of the corresponding oximes. 

After consideration of the mechanism of the Schmidt reaction of carboxylic acids (cf. section III.A)the prediction was made and verified that the Curtins rearrangement would be subject to acid catalysis The charge and bond distribution in the substrate can almost certainly be best represented by 1 and protonation (reaction 7) was believed to form 2 in which the positive charge on the nitrogen of the... 

Degradation reactions of carboxylic acids and their derivatives to amines and their derivatives with one less carbon unit involve rearrangements of a carbon to an electron deficient nitrogen atom as key steps, namely the Hofmann Curtius (C), - Schmidt and Lessen rearrangements, as... 

The Hofmatm, Curtius, Schmidt and Lossen rearrangements generally involve nucleophilic migrations from a carbon to an electron deficient nitrogen center (Scheme 5), giving isocyanates as the initial products, which undergo further reactions as already shown in Scheme 2. 

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... 

The shortcomings of the Beckmann rearrangement at nitrogen as a method to synthesize the isomeric benzazepinones discussed above apply also to the Schmidt method. In this case, another side reaction, the formation of tetrazoles, may occur. The acidic medium used for the rearrangement plays a decisive role in directing the course of the reaction. The rearrangement may in some cases be nonstereospecific. 

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. 

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