Amides N-acylation

Die gemeinsame Condensation von Glycin-ethylester, Carbonsaure-ethylester-imiden und Carbonyl-Verbindungen ffihrt zu 4-Alkyliden- bzw. 4-Aralkyliden-5-oxo-4,5-di-hydro-imidazolen, die durch Reduktion und Hydrolyse in N-Acyl-aminosaure-amide, N-Acyl-aminosauren oder in freie a-Aminosauren fibergeffihrt werden kon-nen2 ... 

Sulfimides from sulfonic acid amides N-Acylation... 

The conversion of alcohols to esters by O-acylation and of amines to amides by N-acylation are fundamental organic reactions. These reactions are the reverse of the hydrolytic procedures discussed in the preceding sections. Section 3.4 in Part B discusses these reactions from the point of view of synthetic applications and methods. 

The second reaction that should be recalled is the aminolysis of esters (p. 479). This reaction leads to the formation of amides by N-acylation ... 

The most common O- and N-acylation procedures use acylating agents that are more reactive than caiboxylic acids or their esters. Carboxylic acid chlorides and anhydrides react rapidly with most unhindered hydroxy and amino groups to give esters and amides, respectively ... 

The modification of the Madelung indole synthesis achieved by introduction of an electron withdrawing group (EWG) at the benzylic carbon atom of the N-acylated-o-alkylanilines has been quite successful. Orlemans et al. reported that indoles were isolated in decent yields when the amides were treated with t-BuOK in THF for a period of 10 minutes at room temperature. ... 

The Bischler-Napieralski reaction involves the cyclization of phenethyl amides 1 in the presence of dehydrating agents such as P2O5 or POCI3 to afford 3,4-dihydroisoquinoline products 2. This reaction is one of the most commonly employed and versatile methods for the synthesis of the isoquinoline ring system, which is found in a large number of alkaloid natural products. The Bischler-Napieralski reaction is also frequently used for the conversion of N-acyl tryptamine derivatives 3 into p-carbolines 4 (eq 2). 

Although the initial radical formed from the reaction of Ce(rV) ion and acetylanilide (AA) and N-p-tolylacet-amide (PTA) has never been observed in the ESR studies, the presence of AA, PTA moieties in the end group of PAN obtained from initiating the CAN-AA, CAN-PTA system have been detected by the FT-IR spectra analysis method. Similar results were observed in the end group analysis of CAN-phenylcarbamate, CAN-N-acyl-N -tolylurea initiation systems. 

The low condensation of diacyl chloride and bis-orf/zo-aminophenol gave a polyhydroxy amide that was submitted to a thermal dehydration.185 187 The two functions of an aminophenol could be acylated, and the question of chemose-lective acylation has been discussed.188 The problem is not O-acylation versus N-acylation because the N-acylated product is tire more stable isomer, but the question is how to control N-monoacylation versus diacylation that could reduce the molecular weight. It has been shown that the condensation in the presence of inorganic salt (LiCl) in NMP gives selectively the N-monoacylated... 

The main application of the enzymatic hydrolysis of the amide bond is the en-antioselective synthesis of amino acids [4,97]. Acylases (EC 3.5.1.n) catalyze the hydrolysis of the N-acyl groups of a broad range of amino acid derivatives. They accept several acyl groups (acetyl, chloroacetyl, formyl, and carbamoyl) but they require a free a-carboxyl group. In general, acylases are selective for i-amino acids, but d-selective acylase have been reported. The kinetic resolution of amino acids by acylase-catalyzed hydrolysis is a well-established process [4]. The in situ racemization of the substrate in the presence of a racemase converts the process into a DKR. Alternatively, the remaining enantiomer of the N-acyl amino acid can be isolated and racemized via the formation of an oxazolone, as shown in Figure 6.34. 

N-Silylated peptide esters are acylated by the acid chloride of N-Cbo-glycine to N-acylated peptide bonds [11]. Likewise, acid chlorides, prepared by treatment of carboxylic acids with oxalyl chloride, react with HMDS 2 at 24°C in CH2CI2 to give Me3SiCl 14 and primary amides in 50-92% yield [12]. Free amino acids such as L-phenylalanine or /5-alanine are silylated by Me2SiCl2 48 in pyridine to 0,N-protected and activated cyclic intermediates, which are not isolated but reacted in situ with three equivalents of benzylamine to give, after 16 h and subsequent chro-... 

N-Acyl-a-amino acids are important compounds in both chemistry and biology. They are easily obtained in a transition metal-catalyzed, three-component domino reaction of an aldehyde, an amide, and CO. Whereas cobalt was mainly used for this process, Beller and coworkers [159] have recently shown that palladium has a... 

Rhodium-catalyzed enantioselective hydrogenation of N-acyl enamides provides access to enantioenriched amides which can be hydrolyzed to the free amines. The synthesis of the substtates is considerably less sttaightforward than that of N-acyl dehydroamino acids, which explains the smaller number of reports devoted to N-acyl enamides. 

It should be pointed out that modem spectrometric techniques, such as f.a.b.-m.s., l.d.-m.s., or even n.m.r. if applied alone, do not allow to the elucidation of the nature of amide-linked acyl groups. This problem can be solved only by using, in addition, chemical or enzymic methodologies such as the ones just described. 

The amidocarbonylation of aldehydes provides highly efficient access to N-acyl a-amino acid derivatives by the reaction of the ubiquitous and cheap starting materials aldehyde, amide, and carbon monoxide under transition metal-catalysis [1,2]. Wakamatsu serendipitously discovered this reaction when observing the formation of amino acid derivatives as by-products in the cobalt-catalyzed oxo reaction of acrylonitrile [3-5]. The reaction was further elaborated to an efficient cobalt- or palladium-catalyzed one-step synthesis of racemic N-acyl a-amino acids [6-8] (Scheme 1). Besides the range of direct applications, such as pharmaceuticals and detergents, racemic N-acetyl a-amino acids are important intermediates in the synthesis of enantiomeri-cally pure a-amino acids via enzymatic hydrolysis [9]. 

The names of AHLs listed in Table 1 are the non-IUPAC description of compounds as N-acyl derivatives of L-homoserine lactone. Alternatively, IUPAC chemical designations for the compounds can be used. These are based on the amide unit as the principal function. Thus AT-(3-oxohexanoyl)-L-homoserine lactone is named as 3-oxo-N-(tetrahydro-2-oxo-3-furanyl)hexanamide. 

A proposed mechanism for this transformation, provided in Scheme 42, is based on the identification of alcohol-carbene complexes by Movassaghi and Schmidt. Mesityl substituted imidazolinylidine carbene acts as a Brpnsted base as transesterification occurs to produce LXVII. Upon O N acyl transfer, the observed product is formed. The evidence provided for this mechanism includes the control experiment in which LXVII is resubjected to the reaction conditions and proceeds with amide formation. A similar mechanism has recently been reported in a theoretical study of transesterification by Hu and co-workers [139], In light of this work, it seems reasonable to suggest a similar that mechanism is operative in the transesterification reactions discussed throughout this section. 

The use of N-acylated-a-amino nitriles, nitrones, or a-amino amides as starting compounds have also been reported. N-Acylated-a-amino nitriles were converted into 5(477)-oxazolones 101 in the presence of ethyl chlorooxoacetate (Scheme 1.21). ... 

TABLE 7.40 N-ACYL DEHYDROAMINO ACID AMIDES FROM AMINOLYSIS OF UNSATURATED 5(4//)-OXAZOLONES, 237... 

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