By the Schmidt reaction

Unlike saUcyhc acid, > -hydroxyben2oic acid does not undergo the Friedel-Crafts reaction. It can be converted in 80% yield to y -aminophenol by the Schmidt reaction, which involves treating the acid with hydra2oic acid in trichloroethylene in the presence of sulfuric acid at 40°C (47). 

The cationic species 4 thus formed reacts with water to give the iminol 5, which tautomerizes to a more stable amide tautomer, the N-substituted carboxylic amide 2. Those steps correspond to the formation of amides by the Schmidt reaction. A side reaction can give rise to the formation of nitriles. 

Ring expansion of thiochroman-4-ones to 5-oxo-2,3,4,5-tetrahydro-1,4-benzothiazepines is accomplished by the Schmidt reaction, cf. Eq. (10).64... 

For example, 2-bromoquinuclidine (80) does not form Grignard reagents and 2-aminoquinuclidine is so unstable that on hydrolysis of its urethans (81) under mild conditions ammonia is lost and polymers of dehydroquinuclidine are formed. The synthesis of 2-bromoquinuclidine (80) was achieved by the Borodin reaction,90 and the urethans (81) were obtained from quinuclidine-2-carboxhydrazide (82) by the Curtius reactions.142 The Curtius reaction with quinucli-dine-4-carboxylic acid derivatives gave 4-aminoquinuclidine (83).143 This compound (83) was also synthesized directly from quinuclidine-4-carboxylic acid by the Schmidt reaction. However, the first method is better, in spite of having more steps. 

The incorporation of [2-14C]pyruvate and [l-14C]acetate into sugars 17 and 18 was investigated.27 Oxidation of the methyl glycosides of sugar 17 with periodate yielded acetaldehyde from the 1-hydroxyethyl branch. The acetaldehyde (2,4-dinitrophenyl)hydrazone was further oxidized by Kuhn-Roth oxidation to acetic acid, which was degraded by the Schmidt reaction to methylamine and carbon dioxide. Periodate oxidation of the methyl glycosides of sugar 18 produced acetic acid from the C-acetyl branch. The acetic acid was isolated, and purified as 1-acetamidonaphthalene. 

The conversion of ketones to amides by the Schmidt reaction has been mentioned elsewhere (method 362). Since the hydrolysis of the amides so obtained proceeds readily, the two steps provide a convenient synthesis of amines from ketones. The yields are often higher than those obtained from the Beckmann rearrangement with subsequent hydrolysis (method... 

Halcomb, R L, Boyer, S H, Danishefsky, S J, Synthesis of the calicheamicin aryltetrasaccharide domain bearing a reducing terminus — coupling of fully synthetic aglycone and carbohydrate domains by the Schmidt reaction, Angew. Chem. Int. Ed. Engl, 31, 338-340, 1992. 

Aliphatic carboxylic acids, even in the case of a sterically hindered carboxylic acid such as (118), are usually converted to the corresponding amines, e.g. (119), by the Schmidt reaction (equation 45). 

More than 100 years later, Comforth, Hunter, and Popjak made use of this reaction in determining the pattern of isotope distribution in cholesterol produced by biosynthesis from labeled acetic acid. One degradation liberated ring A in the form of 2-methylcyclohexanone (1), which was converted by the Schmidt reaction into the lactam (2), which in turn was converted by hydrolysis and methylation into the... 

Schmidt reaction. By the Schmidt reaction cyclobutanecarboxylic acid (Aldrich Chem. Co.) can be converted into cyclobutylamine in one step in high yield.12 On addition of powdered sodium azide to a stirred mixture of chloroform, cyclobutanecarboxylic acid, and concentrated sulfuric acid and heating at 50° for 1.5 hrs., the... 

A novel synthesis of amphimedine 105 has been reported by Prager et al. (89H847 91AJC277). It involves an azido ring expansion of a pyridyla-zafluorenol 185, by the Schmidt reaction, to 5-(4-pyridyl)benzo[a]-... 

Part a can be accomplished by the Schmidt reaction, while part b can be accomplished by a-halogenation followed by ring closure ... 

The reactions of 3-formylchromones, e.g. (186), with various ort/io-substituted anilines (Y = S, O, or NH) provide a high-yielding route to the fused benzo-pyrano-compounds (187)." Various substituted 2,3-dihydro-l,4-benzox-azepin-5(4H )-one-7-acetic acid esters were prepared by the Schmidt reactions of chromanone derivatives." ... 

Hofmaim degradations were carried out on 5pyridine carboxylic acids are treated with sodium azide in an oleum medium, a good yield (69%) of 3-aminopyridine and poorer yields (<30%) of 2- and 4-aminopyridine are realized. 3-Amino-5-nitropyridine is similarly prepared by the Schmidt reaction using 5-nitronicotinic and hydrazoic acid. ... 

Table of Compounds Pbbpabed by the Schmidt Reaction—Continued... 

Tablp of Compounds Pkepabed by the Schmidt Reaction—CorUimted... 

The Curtius, Hofmann (see p. 267), and Schmidt (see p. 307) reactions are in that order decreasingly mild, decreasingly flexible, and increasingly expeditious. The last-named quality varies somewhat with the available starting material, whether the free acid or the ester. The Curtius reaction lends itself to the preparation of isocyanates, sym-and 08-ureas, amides, urethans, and amines at will, and provides a wide choice of experimental conditions. For synthetic purposes the Hofmann reaction can be used only to prepare sym-ureas, urethans, and amines directly, and halting the reaction at a desired intermediate is often not possible. The variety of experimental conditions is narrower and more limited. The Schmidt reaction on carboxylic acids or derivatives has been applied as a preparative method only to the production of amines although urethans and isocyanates have been prepared occasionally by this reaction, it can hardly be considered a preparative method for them. Amides can be prepared by the Schmidt reaction only from ketones. The choice of experimental conditions employable in the Schmidt reaction is narrow. 

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