Amides acylation

Many compounds contain more than one functional group Prostaglandin Ei a hormone that regulates the relaxation of smooth muscles con tains two different kinds of carbonyl groups Classify each one (aldehyde ketone carboxylic acid ester amide acyl chloride or acid anhydride) Identify the most acidic proton in prostaglandin Ei and use Table 1 7 to estimate its pK ... 

Acylation (Section 12 7 and Chapter 20) Reaction in which an acyl group becomes attached to some structural unit in a molecule Examples include the Fnedel-Crafts acylation and the conversion of amines to amides Acyl chloride (Sections 4 1 and 20 1) Compound of the type... 

The use of zeolites can also be very helpful in removing a reaction product that unfavourably influences the yield of the desired product. Thus, in the manufacture of antibiotic cefoxitin, the amide acylation results in the generation of HCI, which can be removed by the addition of molecular sieve 3 A or 4 A, which has a large capacity for HCI (Weinstock, 1986). Other examples are reactions in which products like methanol or water retard the rate and prevent the reaction to reach the desired degree of completion. Molecular sieves capture methanol or water very well. 

The inductive effects shall now be discussed specifically with regard to the various functional moieties such as amides, acyl chlorides, alkyl esters and aryl esters ... 

The Conversion of Organometallic Compounds to Ketones, Aldehydes, Carboxylic Esters, or Amides Acyl-de-metallation, etc. 

Primary amides Acyl chlorides react with hexamethyldisilazane in CH2C12 at room temperature to give, after acid hydrolysis, primary amides in 60-90% yield from the carboxylic acid. 

Peptide thioesters (Section 15.1.10) are generally prepared by coupling protected amino acids or peptides with thiols and are used for enzymatic hydrolysis. Peptide dithioesters, used to study the structures of endothiopeptides (Section 15.1.11), may be prepared by the reaction of peptide nitriles with thiols followed by thiolysis (Pinner reaction). Peptide vinyl sulfones (Section 15.1.12), inhibitors of various cysteine proteases, are prepared from N-protected C-terminal aldehydes with sulfonylphosphonates. Peptide nitriles (Section 15.1.13) prepared by dehydration of peptide amides, acylation of a-amino nitriles, or the reaction of Mannich adducts with alkali cyanides, are relatively weak inhibitors of serine proteases. 

Given the IUPAC name of a carboxylic acid, salt, ester, amide, acyl halide, or anhydride, write its structural formula, and given the structure, write the name. 

Fig. 6.21. In situ activation of a carboxylic acid—i.e., the side chain carboxyl group of protected L-aspartic acid—as the mixed anhydride (B) and its aminolysis to a Weinreb amide. How this Weinreb amide acylates an organolithium compound is shown in Figure 6.44. The acylation of an H nucleophile by a second Weinreb amide is presented in Figure 6.42 and the acylation of a di(ketone enolate) by a third Weinreb amide in Figure 13.64. Figure 6.50 also shows how Weinreb amides of carboxylic acids can be obtained by C,C bond formation.

Preparation sn2 Esterification sn2 Reductive Amidation Acylation Carbonoylation Phosphorylation Acetalization ... 

From amide-acylating reagent adducts and amines or amine derivatives... 

C2BioHi2 derivatives with, e.g., R = ester, amine, amide, acyl halide, halogen, ether, alkyl, aryl, alkenyl or alkynyF , although a dialkyne will lead to some bis-carborane ... 

Lij>(>ic add Lij><>amide Acyl group aetiv[Pg.1004]

Owing to the slow in vivo cleavage rate of the A-substituted amides, acylation of amines is generally not recommended. Better possibilities are offered by activated amides, peptides, imines and soft quaternary anunonium salts. However, the use of simple A-acyl derivatives must not systematically be discarded. The A-benzoyl- or A-pivaloyl... 

Acylaminoalcohols N-Acylcarboxylic acid amides Acyl formimidates N-Acyliminoesters Acylisocyanates Acyloximes... 

Amides Acyl ureas Acids/bases Active-H... 

Xia et al. [63] developed new acyl AAS having the general structure a-amino-(Ai-acyl)-P-alkoxypropionate. The structure-function relationship of the anionic amino-alkoxypropionates was evaluated, with an emphasis on their antimicrobial properties. The anionic amino-alkoxypropionate was synthesized, starting from propionic acid methyl ester, through alkoxylation with fatty alcohol, bromination, saponification, amidation, acylation with R OCl (acyl chloride), and saponification to obtain the final product. For the detailed procedure, see Xia et al. [63]. 

The amide acyl C atom is less electrophilic than that of the other carboxylic acid derivatives. 

The C3 amide-acyl group is critical but may be aromatic or alkyl in nature. 

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