Amide, synthesis

Interestingly, lipase-catalyzed acyl transfer onto SH-groups (corresponding to ester thiolysis in analogy to aminolysis) does not take place [289]. As a result, the resolution of sec-thiols is not feasible by this method and has to be performed via hydrolysis or alcoholysis of the corresponding thioesters [290-292]. 

Aryl-alkyl Me, Et, c-Pr Ph, p-CI-CeH4, o.p-dl-CI-CeHa, m- or p-MeO-CgH4, p-Me-CgH4, 1-naphthyl, 2-pyrldyl. 

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Dicyclohexylcarbodiimide is a solid material, the Lewis structure for which resembles that of ketene. The molecule is a widely used catalyst for amide synthesis and other dehydration reactions. 

Because FIC1 is formed during the reaction, two equivalents of the amine must be used. One equivalent reacts with the acid chloride, and one equivalent reacts with the HC1 by-product to form an ammonium chloride salt. If, however, the amine component is valuable, amide synthesis is often carried out using 1 equivalent of the amine plus 1 equivalent of an inexpensive base such as NaOH. For example, the sedative trimetozine is prepared commercially by... 

Irimescu and Kato have recently described an interesting example of enzymatic KR in ionic liquids instead of organic solvents (Scheme 7.4) [12]. The resolution with CALB is based on the fact that the reaction equilibrium was shifted toward the amide synthesis by the removal of water under reduced pressure. Nonsolvent systems have been also employed in this enantioselective amidation processes, reacting racemic amines with aliphatic acids. The best reaction conditions for the conversion of acids to amides was observed using CALB at 90 °C under vacuum. Meanwhile, no... 

Scheme 7.46 Solid-supported amide synthesis employingthe safety-catch principle.

Sauer and coworkers have presented the use of polystyrene-bound carbodiimide for convenient and rapid amide synthesis [124], An equimolar mixture of 1-methy-lindole-3-carboxylate, the requisite amine, and 1-hydroxybenzotriazole (HOBt) in... 

Scheme 7.103 Amide synthesis utilizing polymer-bound carbodiimide.

In a detailed investigation, Turner and coworkers have described the preparation and application of solid-supported cyclohexane-1,3-dione as a so-called capture and release reagent for amide synthesis, as well as its use as a novel scavenger resin [125]. Their report included a three-step synthesis of polymer-bound cyclohexane-1,3-dione (CHD resin, Scheme 7.104) from inexpensive and readily available starting materials. The key step in this reaction was microwave-assisted complete hydrolysis of 3-methoxy-cyclohexen-l-one resin to the desired CHD resin. 

Scheme 7.109 Amide synthesis utilizing a reusable polymer-supported acylation reagent.

Scheme 7.111 Recyclable polymer-supported imides for amide synthesis.

Scheme7.112 Polymer-supported Mukaiyama reagent for amide synthesis.

The first example describes the synthesis of a pyrimidine derivative. Starting from a, 3-unsaturated ketones (see Schemes 1, 8), a library of different heterocycles was prepared in research (Felder and Marzinzik 1998). In preparation for any large-scale synthesis, the availability of starting materials is always considered (Lee and Robinson 1995). For this work, we had to replace Rink amide resin B (Rink 1987), which was used by our colleagues in research for the synthesis of pyrimidine 1 due to its unavailability in large quantities (see Fig. 1). It was replaced with the Rink amide acetamido resin 4, which is well established in peptide amide synthesis (Bernatowicz et al. 1989) and easily accessible. 

Similarly, heterogeneous amide synthesis can be elegantly achieved in cartridges filled with silica functionalized with carbodiimide. The process outlined in Figure 3.16 yields quantitative conversion and 98.8% purity by reacting benzoic acid with phenylethylamine. 

Figure 3.16 Using SiliaPrep Carbodiimide for amide synthesis.

Allais C, Constantieux T, Rodriguez J (2009) Highly Efficient Synthesis of trans-beta, gamma-Unsaturated alpha-Keto Amides. Synthesis 2523-2530... 

Building blocks are amphiphiles, which have a delicate balance between the hydrophilic and hydrophobic group crucial to facilitate self-assembly. The peptide component serves to precisely control this balance, and the enzymatic reaction serves to alter it in favour of self-assembly. As illustrated in Fig. 3, the molecular switch may involve (1) phosphatase-catalysed removal of a (phosphate) group from the precursor to control the electrostatic balance (reaction (i) in Fig. 3) (2) hydrolysis of alkyl esters by hydrolases to change the amphiphilic balance (reaction (ii) in Fig. 3) or (3) condensation between two non-self-assembling precursors via a condensation reaction, e.g. involving protease-catalysed amide synthesis to alter the hydrophilic/hydrophobic balance (reaction (iii) in Fig. 3). A number of examples of each type are summarised in Table 1. 

Sodium Amide. Synthesis of j8-Keto Esters. J. Amer. chem. Soc. 66, 1768 (1944). 

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