Beckmann rearrangement amide synthesis

A modification of this method, related to the Beckmann rearrangement, entails treatment of a ketoxime with one equivalent of CDI, then four to five equivalents of a reactive halide such as allyl bromide or methyl iodide (R3X) under reflux in acetonitrile for 0.5-1.5 h. Quatemization of the imidazole ring effectively promotes the reaction by increasing the electron-withdrawing effect. The target amides then are obtained by hydrolysis. High yields, neutral conditions, and a very simple procedure make this modification of the synthesis of amides by azolides a very useful alternative. 1243... 

The stereochemical use of the Beckmann rearrangement in assigning configuration to ketoximes has already been referred to, and it also has a large-scale application in the synthesis of the textile polymer Nylon-6 from cyclohexanone oxime (78) via the cyclic amide (lactam, 79) ... 

Acidic zeolites, K-10 clay and silica are highly active and selective catalysts for the dehydration/Beckmann rearrangement reactions of aldoxhnes (benzaldoxime and 4-methoxybenzaldoxime) for the synthesis of nitriles and amides . 

One of the most famous examples of intramolecular attack of oxygen on the nitriUnm ion intermediate was observed in the Beckmann rearrangement of Erythromycin oxime derivatives and was used in the discovery and synthesis of the commercial macrolide antibiotic Azithromycin 464. In fact, the Beckmann rearrangement of Erythromycin A 9( )-oxime 460 produced only small amounts (5%) of the expected amide 463, along with two isomeric imino ethers (461 and 462) in a fair yield (38 and 43%) (equation 198). 

Such condensation reactions are also promoted by certain trTvalent phosphorus compounds, e.g. triphenyl phosphite (2) or diphenyl ethylphosphonite (3), or to a lesser extent by pFosphonate esters, e.g. diphenyl n-butylphosphonate (3). "Bates reagent," p-oxobi s[tri s(cTi methyl ami no)phosphoni urn] bi s-tetra-f1uoroborate (2) may also be used to activate the carboxyl function towards amide bond formation during peptide synthesis (4) and to bring about the Beckmann rearrangement of ketoximes (F). 

Thermal dehydration of o- (acylamino)phenols is the method of choice for the preparation of benzoxazoles (equation 96) and other annulated oxazoles. 0,iV-Diacyl derivatives of o-aminophenols cyclize at lower temperatures than do the monoacyl compounds. The synthesis is often carried out by heating the aminophenol with the carboxylic acid or a derivative, such as the acid chloride, anhydride, an ester, amide or nitrile. The Beckmann rearrangement of oximes of o-hydroxybenzophenones leads directly to benzoxazoles (equation 97). 

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... 

His, S., Meyer, C., Cossy, J., Emeric, G., Greiner, A. Solid phase synthesis of amides by the Beckmann rearrangement of ketoxime carbonates. Tetrahedron Lett. 2003, 44, 8581-8584. 

The preparation of this oxime is the second step in this sequence to obtain the aromatic nitrile target molecule. In Experiment [E2] you are going to convert the aromatic aldehyde formed in Experiment [El] into an 0-phenylated oxime, which on treatment with base in Experiment [E3] yields the desired nitrile via an elimination reaction. Oxime formation is also involved in the well-known Beckmann rearrangement (see Experiment [6adv])/ which is used for the synthesis of amides. 

The one pot synthesis of amide 18 was accomplished within 2 min. by P205/Si02 catalyzed Beckmann rearrangement of the ketone 17 under microwave irradiation." Other ketones such as cyclohexanone, benzophenone, acetophenone and benzil furnished the rearranged products in excellent yields. 

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... 

A synthesis of riburonic acid derivatives from simple precursors is outlined in Scheme 3 resolution of the intermediate acids was effected and both d> and L-products were obtained. Other studies in the D-riburonic acid series reported the glycosyl bromide (4) and thence the corresponding azide the amide (5) led to the unusual A-heterocyclic derivative (6). Beckmann rearrangement of the oxime (7) in the presence of copper(u) acetate gave the amide (8), dehydration of which yielded the nitrile (9). ... 

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... 

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