Schmidt rearrangement with ketones

Schmidt reaction of ketones, 7, 530 from thienylnitrenes, 4, 820 tautomers, 7, 492 thermal reactions, 7, 503 transition metal complexes reactivity, 7, 28 tungsten complexes, 7, 523 UV spectra, 7, 501 X-ray analysis, 7, 494 1 H-Azepines conformation, 7, 492 cycloaddition reactions, 7, 520, 522 dimerization, 7, 508 H NMR, 7, 495 isomerization, 7, 519 metal complexes, 7, 512 photoaddition reactions with oxygen, 7, 523 protonation, 7, 509 ring contractions, 7, 506 sigmatropic rearrangements, 7, 506 stability, 7, 492 N-substituted mass spectra, 7, 501 rearrangements, 7, 504 synthesis, 7, 536-537... 

In addition to the Beckmann reaction, the Schmidt rearrangement is used to generate M-alkylated lactams, too. Alkyl azides 231 react with the cyclic ketones (and aldehydes) in the presence of proton or Lewis acids. On running the inter-molecular reactions, in most cases symmetric ketals 230 have been converted... 

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

Of equal importance to the Beckmann rearrangement for the preparation of azepines and azepinones is the Schmidt reaction of ketones. Again, however, with unsymmetrically substituted cyclohexanones or with bicyclic ketones such as a-tetralone, two azepines are possible, a -Substituted cyclohexanones invariably yield the product of attack by azide ion at the least hindered side of the protonated ketone as exemplified in Scheme 19 (B-67MI51600). 

The group of rearrangements brought about by treatment of aldehydes, ketones, or carboxylic acids with hydrogen azide are known as Schmidt rearrangements. All are acid-catalyzed and all involve addition of HN3 to the carbonyl group followed by dehydration. They are shown in Equations 6.58-6.60. 

Aube and co-workers have found that enolizable ketones react with benzyl azide in triflic acid to yield /V-(phenylamino)-methylated products [Eq. (5.354)]. The transformation is an aza-Mannich reaction interpreted with the involvement of the Mannich reagent A -phenyl iminium ion 295 formed in situ in a Schmidt rearrangement. Cyclic tertiary alcohols react with alkyl azides in triflic acid to yield N-alkylamines (296, 297)983 [Eq. (5.355)]. The Schmidt rearrangement was used to transform Merrifield resin into amino-polystyrene resin by reacting the azido derivative in excess triflic acid (CH2CI2, 0°C).984... 

Nitrilium ions are generally indicated as discrete intermediates in the Beckmann rearrangement of oximes (equation 37, Y = OH2) and in the Schmidt rearrangement (equation 37, Y = N2) of ketones and aldehydes with hydrogen azide. The first stage of these reactions has been defined as an ionization by rearrangement process through a transition state of type 183 (Smith, 1963). 

Upon treatment with sodium azide in 98% sulfuric acid, ketone 79 underwent a Schmidt rearrangement, which through the intermediate 80 gave rise to the 1,3-diazocine 81 (50%) and 1,4-diazocine 82, as minor product (20%) (Scheme 19) <1995JME2946>. 

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... 

Benzaldehyde undergoes the Schmidt reaction with formation of benzonitrile in 70% yield in this case no C—>N rearrangement is involved. Ketones, including... 

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... 

An unusual Schmidt reaction has been observed with ketone (56) <95H(40)223>. When the reaction is carried out using hydroxylamine 0-sulfonic acid/formic acid, the expected ring expansion to the tetrahydropyridinones occurs. With hydrazoic acid, however, the unexpected 1,3-diazepine system is obtained (58). This observation is rationalized by the intermediate (57), formed by addition of hydrazoic acid to the initially formed lactam, which then undergoes a Huisgen rearrangement. 

Schmidt rearrangement of an azido ketone. Thus, 6,7-dimethoxy-2-tetralone (219) has been reacted with methyl ( )-7-iodo-2-heptenoate (220) affording stereoselectively the Cl-spiroketone 221 in 48% yield. After transformation of the latter to the azido derivative 222 the tetracyclic lactam 223 was obtained under ring expansion possessing the schelhammeridine core. Finally, LiAlH4 reduction smoothly provides the ( )-3-demethoxy-l,2-dihydrocomosidine base 224 (772) (Scheme 41). 

Intramolecular rearrangements of polymers with ketone groups were subjects of several studies. The Schmidt and Beckmann rearrangements were carried out on copolymers of ethylene and carbon... 

The Schmidt rearrangement of a six-membered benzo-fused ketone with sodium azide yielded benzazepinone derivatives en route to the synthesis ofa library of tubulin-polymerization inhibitors (14JME1390).The reaction of N-nitrosoaniUnes 16 with 2-vinyloxirane 17, catalyzed by rhodium (111), followed by Raney-nickel-catalyzed hydrogenation led to a series of benzazepane derivatives 18 via a reductive amination of a proposed aldehyde intermediate (140L1200). 

The Schmidt reaction of carboxylic acids with hydrazoic acid has the advantage over Curtius rearrangement that it is only one step from the acid to the amine, but the conditions are more drastic (usually sulphuric acid plus sodium azide). Under these harsh conditions, the isocyanate intermediate is rarely isolated. For these reasons, the Curtius rearrangement is frequently employed to convert acids to amines. The Schmidt reaction of ketones with hydrazoic acid is a powerful method for the synthesis of amides and lactams. TTiis process is somewhat related to the Beckmann rearrangement of oximes however, the Schmidt reaction is more succinct, allowing the conversion of ketones to amides in a single operation. Considering its widespread... 

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