Amides intermediate

Following formation of the amide intermediate, a second nucleophilic addition of hydroxide ion to the amide carbonyl group then yields a tetrahedral alkoxide ion, which expels amide ion, NHZ-, as leaving group and gives the car-boxylate ion, thereby driving the reaction toward products. Subsequent acidification in a separate step yields the carboxylic acid. We ll look at this process in more detail in Section 21.7. 

The synthesis of (6 5 6) fused heterocycles may involve one-pot double intramolecular cyclocondensations. A typical example of this reaction is the formation of amide intermediate 247 from 246, which further cyclizes to give pyridopurine derivative 248 (Scheme 13) <1995TL4249>. 

In a deliberate attempt to trap the carbanion/amide intermediates formed en route to the homoamido inverse crown complexes, [ (TMP)(/z-Bu)(/x-TMP)NaMg(TMEDA) ] 432 (Figure 38) was isolated and characterized.440 This complex spans the superbase and inverse crown structural modalities. 

The HCN exchange itself proceeds through a trigonal bipyr-amidal intermediate [Li(NCH)5]+ reached via a late transition state. The entering HCN molecule approaches the lithium cation directly, and pushes three coordinated solvent molecules away toward the equatorial positions. In line with the experimental observation of a very fast exchange process, the computed... 

Scheme 25.2 Hydrogenation of the /tdehydro amino acid amide intermediate for MK-0431.

Commercially available hyperbranched polymer, a poly(ester-amide) is currently being marketed by DSM under the product name Hybrane [13] (Figure 8.2). It is also a hydroxyl-functionalized product, but contains both amide and ester linkages. The synthesis is accomplished in two steps cyclic anhydrides are reacted with diisopropanolamine to give an amide-intermediate, possessing two hydroxyl groups and one carboxylic acid. The subsequent polymerization takes places via an oxazolinium intermediate which results in the formation of a... 

A strain of Pseudomonas aeruginosa has been recently described, which shows the opposite enantioselectivity, converting racemic arylaminonitriles efficientiy into the D-amino acids. Again, whole-cell biocatalysis worked well, the cells being entrapped in alginate beads. It is unclear whether this biotransformation involves an amide intermediate. 

AU the products resulting from acid-catalysed solvolysis of A-acetoxy-A-butoxybenz-amides in acetonitrile-water mixtures were derived from the A-butoxy-A-hydroxybenz-amide intermediate (103), which is itself an anomeric amide and is the amide equivalent of a hemi-acetal . Decomposition reactions of 103 under acidic conditions are presented in Scheme 20. 

Construction of pyrazine rings from a-amino nitriles has been sometimes completed through multistep reactions. For example, 2-aminopyrazine 1-oxide 163 is synthesized via amide intermediate 162 formed by reaction of methyl a-aminocyanoacetate with a-oximino carboxylic acid (Scheme 45) <1994H(38)1581>. 

The magnesium bis(amide) Mg(TMP)2 (TMP = 2,2,6,6-tetramethylpiperidide) has been shown to be a useful base in the selective deprotonation of arenes to produce aryhnagne-sium amide intermediates . For example, reaction of Mg(TMP)2 with methyl benzoate... 

With an improved synthesis of the triazole fragment in hand, which would allow for its introduction much earher in the synthesis, we started searching for a direct preparation of the P-keto amide intermediate from trifluorophenylacetic acid (9). This type of transformation has been accomplished in the past using acyl Mel-drum s acid adducts [16]. This methodology involves reaction of Meldrum s acid with activated carboxyhc acids followed by decarboxylation in the presence of nucleophiles such as alcohols or amines (Scheme 5.13). The abihty of readily avail-... 

The hypothesis of a protonated amide intermediate is supported by the observation of the pH-rate maxima since once the amide is fully protonated, a further, increase in acid concentration decreases the activity of water in the medium188, the rate-determining step being the attack of a water molecule on the conjugate acid of the amide203-205. If the hydrolysis is of the form,... 

A three-site system for peptide synthesis around a cobalt(III) complex has been studied. Instead of a quadridentate ligand as used in the above experiments, Wu and Busch chose the tridentate ligand diethylenetriamine. The formation of dipeptide and tetrapeptide complexes is shown in Scheme 92.360 The ester carbonyl group in the 0-bonded amide intermediate (127) cannot be activated by coordination because it cannot reach the metal ion. Isomerization to the jV-bonded amide complex (128) occurs with base and enables coordination and therefore activation of the ester carbonyl group. 

Initial explanations in terms of an associative SN2-type reaction proved untenable, and the reaction is now thought to involve deprotonation of a co-ordinated amine (Fig. 2-17). This is the SN1 cb or Deb mechanism. The key step is the formation of the amide intermediate, [Co(NFl3)4(NH2)Cl]+, which undergoes halide loss to generate the reactive five-co-ordinate intermediate [Co(NH3)4(NH2)]2+ (2.2) (Fig. 2-18). 

The Willgerodt-Kindler reaction has been used to synthesize O-methyldauri-cine (17). The product was evidently a mixture of diastereomers (272-274). A similar approach provided stebisimine (409), obaberine (80), and isotetrandrine (236) (275). In a variation, enamine thioether 410 reacted with 411 to generate bis amide intermediates for the synthesis of 80, 236, and 409 (276). 

Salmeen, A., J.N. Andersen, M.P. Myers, T.C. Meng, J.A. Hinks, N.K. Tonks, and D. Barford. 2003. Redox regulation of protein tyrosine phosphatase IB involves a sulphenyl-amide intermediate. Nature. 423 769-73. 

In the original process using tin amides, transmetallation formed the amido intermediate. However, this synthetic method is outdated and the transfer of amides from tin to palladium will not be discussed. In the tin-free processes, reaction of palladium aryl halide complexes with amine and base generates palladium amide intermediates. One pathway for generation of the amido complex from amine and base would be reaction of the metal complex with the small concentration of amide that is present in the reaction mixtures. This pathway seems unlikely considering the two directly observed alternative pathways discussed below and the absence of benzyne and radical nucleophilic aromatic substitution products that would be generated from the reaction of alkali amide with aryl halides. 

The amide intermediate was dissolved in 10 xl CH2C12, then treated with acetyl chloride and 13 xl Af,Af-diisopropylethylamine. It was then partitioned between EtOAc and water and the organic layer isolated, then dried, and concentrated. The residue was then dissolved in water/dioxane, 1 1, followed by 10 mg K2C03 and then stirred 2 hours. The mixture was partitioned between EtOAc and the organic layer isolated. This organic layer was dried, triturated with diethyl ether, and 20 mg of product isolated. 

The initial catalyst systems described above were effective with aryl bromides and a relatively narrow array of amines, although these procedures found utility in the preparation of diaminofluorenes [22], poly(aryleneamines) [23], certain iV-aryl-aza-crown ethers [24], N -arylpiperazines [25], and diaminobenzenes [26] (Fig. 1). These original methods often proved reasonably effective in the coupling of cyclic amines. Presumably, cyclic amines are less challenging substrates for the palladium-catalyzed coupling because the cyclic palladium (II) amide intermediates are less prone to /1-H elimination compared to their acyclic counterparts. 

Presumably, the use of a bidentate ligand such as ( )-BINAP or DPPF results in the occupation of a vacant coordination site, preventing -hydride elimination of the Pd (II) amide intermediate [53]. Dissociation of the imine and C-H bond reductive elimination results in formation of the reduced aryl bromide. If this -hydride elimination is rapid relative to reductive elimination and reversible, then significant erosion of the enantiomeric excess of optically active a-substituted amines maybe observed during the reaction (Scheme 3). 

Nitrile biodegradation is performed by a variety of microorganisms and proceeds through two different enzymatic pathways direct transformation to carboxylic acids and ammonia, with some exceptions, catalyzed by a nitrilase (EC 3.5.5.1) [1-3] or a two-step reaction, the first catalyzed by nitrile hydratase (EC 4.2.1.84) that produces an amide intermediate, which is further hydrolyzed to the acid and ammonia by an amidase (EC 3.5.1.4) [4, 5],... 

Thu conditions required for alkaline hydrolysis of a nitrile arc severe (KOH, 200 C>, so the amide intermediate can sometimes be isolated if milder conditiona are used. 

Electron-rich arenes are suitable nucleophiles for this reaction as well. Thus, the addition of arenes to imines has been described in both intra- (equation 121) and intermolecular (equation 122) fashion catalyzed by AuCb/AgOTf The yields were increased in the intramolecular version by acylation of the amide intermediate to give acylamides. In... 

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