Amides acylation with

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]. 

Pantothenic acid, sometimes called vitamin B3, is a vitamin that makes up one part of a complex coenzyme called coenzyme A (CoA) (Figure 18.23). Pantothenic acid is also a constituent of acyl carrier proteins. Coenzyme A consists of 3, 5 -adenosine bisphosphate joined to 4-phosphopantetheine in a phosphoric anhydride linkage. Phosphopantetheine in turn consists of three parts /3-mercaptoethylamine linked to /3-alanine, which makes an amide bond with a branched-chain dihydroxy acid. As was the case for the nicotinamide and flavin coenzymes, the adenine nucleotide moiety of CoA acts as a recognition site, increasing the affinity and specificity of CoA binding to its enzymes. 

The reaction of methane tricarboxylate with indoline 342 gave the tricyclic derivative 361 which can be transformed to the amide derivatives 362 (97JHC969). Alkylation of the iV-benzyl indoline 360 with pentafluor-oacetone gave 363 which upon debenzylation and subsequent acylation with diketene followed by cyclization gave 364. Other haloacetones were used to prepare different halogenated derivatives (79BEP872311) (Scheme 63). 

Schiff s base (j ) derived by reaction of p-chloro-anil ine and borohydride followed by acylation with phenylacetyl chloride produces amide 22,. Selective hydrolysis with HBr followed by alkylation with isopropyl bromide completes the synthesis of lorcainide (20). ... 

Many aldehydes and ketones have been converted to g m-difluoro compounds with sulfur tetrafluoride (SF4), " including quinones, which give 1,1,4,4-tetra-fluorocyclohexadiene derivatives. With ketones, yields can be raised and the reaction temperature lowered, by the addition of anhydrous HF. Carboxylic acids, acyl chlorides, and amides react with SF4 to give 1,1,1-trifluorides. In these cases the first product is the acyl fluoride, which then undergoes the ge i-difluorination reaction ... 

Azolides can also be used in amide syntheses with very good results when incorporated into copolymers. For example, reactions with l-acyl-4-vinylimidazole/divinylbenzene (96 4) copolymer in solvents like 1,4-dioxane or acetonitrile provide amides in good yields within 1-4 h [1221... 

Alkylation of piperazine with the amide formed by reaction of chloroacetyl chloride with pyrrolidine gives amide 133. Acylation with 3,4,5-trimethoxy-... 

In this series, too, replacement of the N-methyl by a group such as cyclopropylmethyl leads to a compound with reduced abuse potential by virtue of mixed agonist-antagonist action. To accomplish this, reduction of 24 followed by reaction with tertiary butylmagnesium chloride gives the tertiary carbinol 27. The N-methyl group is then removed by the classic von Braun procedure. Thus, reaction with cyanogen bromide leads to the N-cyano derivative (28) hydrolysis affords the secondary amine 29. (One of the more efficient demethylation procedures, such as reaction with ethyl chloroformate would presumably be used today.) Acylation with cyclopropylcarbonyl chloride then leads to the amide 30. Reduction with lithium aluminum hydride (31) followed by demethylation of the phenolic ether affords buprenorphine (32).9... 

Acyl-transfer reactions are some of the most important conversions in organic chemistry and biochemistry. Recent work has shown that adjacent cationic groups can also activate amides in acyl-transfer reactions. Friedel-Crafts acylations are known to proceed well with carboxylic acids, acid chlorides (and other halides), and acid anhydrides, but there are virtually no examples of acylations with simple amides.19 During studies related to unsaturated amides, we observed a cyclization reaction that is essentially an intramolecular acyl-transfer reaction involving an amide (eq 15). The indanone product is formed by a cyclization involving the dicationic species (40). To examine this further, the related amides 41 and 42 were studied in superacid promoted conversions (eqs 16-17). It was found that amide 42 leads to the indanone product while 41... 

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 ... 

Aliquat is an efficient catalyst for the acetoacetylation of amines by diketene. The initially formed amides react with an excess of the diketene to form, after cyclization of the secondary product, 1-substituted 3-acetyl-4-hydroxy-6-methylpyrid-2-ones [39]. Amides react under similar conditions with diketene to form A-acyl aceto-acetamides, which react further with a second molecule of diketene to yield, after cleavage of the A-acyl group, 3-acetyl-4-hydroxy-6-methylpyrid-2-one [39]. 

In neutral or alkaline buffer solution at 37°, the hydrolytic breakdown of A-formylbenzamide (4.166, R=H) produced only benzamide (4.167). In contrast, the higher homologues were hydrolyzed at the two amide bonds, with benzamide (4.167) and benzoic acid (4.168) formed in a 3 2 ratio. Plasma-catalyzed hydrolysis occurred predominantly at the distal amide bond to produce benzamide. Under these conditions, hydrolysis was very rapid for N-formylbenzamide (80% hydrolysis in 15 min, i. e., ca. 500-fold faster than under abiotic conditions). The rate of enzymatic hydrolysis was also markedly influenced by the length of the A-acyl group, and decreased in the order H>Me>Bu>Pr>Et. 

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