Schmidt reaction amide synthesis

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... 

The Schmidt reaction is closely related to the Beckmann reaction (equation 34). Acyclic and cyclic ketones are transformed to amides and lactams by treatment with hydrogen azide. With bridged bi-cyclic ketones, the regioselectivity of the migration is opposite to the direction of the Beckmann reaction. The Schmidt reaction has been applied to asymmetric synthesis starting from optically active a,a-dialkylated -keto esters. High chemical and optical yields have been obtained (equation 35). ... 

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... 

The intramolecular Schmidt reaction has provided a solution to the problem of bridgehead lactam synthesis. The bridged lactams incorporate a twisted amide unable to achieve standard planar geometry and can undergo rapid hydrolysis. Reaction of ketoazide with HBF4 in ether results in a mixture of two latams from which the desired quinoclidone 92 is isolated in 38% yield after recrystalization. ... 

Zhang and Tu employed the intramolecular Schmidt reaction as a key step in their total synthesis of ( )-maistemonine (6) and ( )-stemonamide (7) [7]. Treatment of 2,2-disubstituted cyclohexadione 4 with TiC provided the desired bicyclic amide 5 containing the central perhydroazaazulene ring system. The remarkable stereoselectivity was accounted for by invoking the preferred conformation B over A, the latter suffering from repulsive steric interaction between the allyl and the alkynyl substituents (Scheme 4.2). 

Amides are common structures and they are important and versatile synthons to prepare pharmaceuticals, agrochemicals, materials and some specialty chemicals. Many methods have been developed to synthesize primary amides, secondary amides as well as tertiary amides. The traditional process to construct amide bond is the acylation of amines with carboxylic acid or carboxylic acid daivatives such as acid chlorides as well as anhydrides [1, 2]. Furthermore, the Schmidt reaction [3] and Beckmann rearrangement [4] also have been well developed for the amide synthesis. Recently, some reviews have been well summarized the synthesis routes of these amides [5-17]. In this chapter, we will focus on the recent progresses about amide synthesis only by N, NH, or NH2 atoms incorporation nitrogenation strategy via C-H and/or C-C bond cleavage. A series of nitrogen sources such as sodium... 

Scheme 3.11 Plausible mechanism for the amide synthesis via Schmidt reaction...

The extension of the salt-acid,27 phenylhydrazide,28 and amide rules29 to the derivatives of the 2-(hydroxymethyl) sugars by Schmidt and Weber-Molster30 indicated that the configuration of C2 in hamamelonic acid is the same as that of D-ribonic acid. Finally, the d-ribo configuration of the sugar was established by the synthesis of hamamelonic acid and its C2 epimer from D-ery/ftro-pentulose31 by the cyanohydrin reaction of Fischer and Kiliani. 

Chiral crystals generated from non-chiral molecules have served as reactants for the performance of so-called absolute asymmetric synthesis. The chiral environments of such crystals exert asymmetric induction in photochemical, thermal and heterogeneous reactions [41]. Early reports on successful absolute asymmetric synthesis include the y-ray-induced isotactic polymerization of frans-frans-l,3-pentadiene in an all-frans perhydropheny-lene crystal by Farina et al. [42] and the gas-solid asymmetric bromination ofpjp -chmethyl chalcone, yielding the chiral dibromo compound, by Penzien and Schmidt [43]. These studies were followed by the 2n + 2n photodimerization reactions of non-chiral dienes, resulting in the formation of chiral cyclobutanes [44-48]. In recent years more than a dozen such syntheses have been reported. They include unimolecular di- r-methane rearrangements and the Nourish Type II photoreactions [49] of an achiral oxo- [50] and athio-amide [51] into optically active /Mactams, photo-isomerization of alkyl-cobalt complexes [52], asymmetric synthesis of two-component molecular crystals composed from achiral molecules [53] and, more recently, the conversion of non-chiral aldehydes into homochiral alcohols [54,55]. 

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