Acylation carboxylic acids

The acyl group of the carboxylic acid acyl chloride or acid anhydride is trans ferred to the oxygen of the alcohol This fact is most clearly evident m the esterification of chiral alcohols where because none of the bonds to the chirality center is broken m the process retention of configuration is observed... 

The chemistry of the carbonyl group is probably the single most important aspect of organic chemical reactivity Classes of compounds that contain the carbonyl group include many derived from carboxylic acids (acyl chlorides acid anhydrides esters and amides) as well as the two related classes discussed m this chapter aldehydes and ketones... 

The negatively charged oxygen substituent is a powerful electron donor to the carbonyl group Resonance m carboxylate anions is more effective than resonance m carboxylic acids acyl chlorides anhydrides thioesters esters and amides... 

For less hindered carboxylic acids acylation of the imidate requires only 5 minutes. With this modification the /V-(a-methoxybenzyl)amides are prepared according to the above-mentioned procedure [R = CH3, CH(CH,)2. CH(CH, )OAc, CH(C H2)OAc yield 85-88%]. 

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 ... 

C. Reactions with carboxylic acids, acyl chlorides, acid anhydrides, and W-methoxyamides to give ketones... 

Acylation reactions can be done at the nucleophilic sites on pyrimidines using activated forms of carboxylic acids. Acylation of functional groups in nucleotides typically is used for protection during synthesis (Reese, 1973). However, for bioconjugate applications, the reactivity of native groups on pyrimidines is not as great as that obtained using an amine-terminal spacer derivative, such as those described in Chapter 27, Section 2.1. Yields and reaction rates are typically low for direct acylation or alkylation of pyrimidine bases, especially in aqueous environments. 

As in Section 5.06.9.1, the assignments are sometimes arbitrary. Important routes to oxadiazoles, aminooxadiazoles, oxadiazolinones, and oxadiazolinethiones involving the reaction of hydrazides RCONHNH2 with carboxylic acids, acyl chlorides, alkyl esters, or trialkyl orthoesters are described in Section 5.06.9.2.1, reactions with carbon disulfide... 

Glycine conjugation Carboxylic acids Acyl-CoA amino acid N-transferase Glycinamide conjugates... 

Coenzyme A (see also p. 106) is a nucleotide with a complex structure (see p. 80). It serves to activate residues of carboxylic acids (acyl residues). Bonding of the carboxy group of the carboxylic acid with the thiol group of the coenzyme creates a thioester bond (-S-CO-R see p. 10) in which the acyl residue has a high chemical potential. It can therefore be transferred to other molecules in exergonic reactions. This fact plays an important role in lipid metabolism in particular (see pp. 162ff), as well as in two reactions of the tricarboxylic acid cycle (see p. 136). 

Another important part of Organic 11 is carbonyl chemistry. We look at the basics of the carbonyls in Chapter 9. It s like a family reunion where 1 (John, one of your authors) grew up in North Carolina — everybody is related. You meet aldehydes, ketones, carboxylic acids, acyl chlorides, esters, cimides, and on and on. It s a quick peek, because later we go back and examine many of these in detail. For example, in Chapter 10 you study aldehydes and ketones, along with some of the amines, while in Chapter 11 we introduce you to other carbonyl compounds, enols and enolates, along with nitroalkanes and nitriles. 

Conversion of Diazonium Salts to Aldehydes. Ketones, or Carboxylic Acids Acyl-de-diazoniation, etc. 

Nucleophilic attack on the carbonyl group of such a compound results in displacement of a good leaving group, Cl or R-COO. Nature has followed the same approach in forming from carboxylic acids acyl phosphates or acyl-CoA derivatives. 

The chroman ring system is stable to organometallic reagents, for example in the formation of the tertiary alcohol (690) in high yield (63HCA650), and to the usual interconversion of carboxylic acid, acyl chloride, carboxamide and nitrile. 

Lysine, 4-amino Carboxylic acids, acyl hahdes, Amide formation... 

Carboxylic acids, acyl chlorides, and sulfonyl chlorides used for deri-vatization of 4-aminophenylalanine and >-4-am i n op h e ny I a I a n i n e are as follows 5-hydantoinacetic acid, / ran, v - 4 - co t i n i n ec a r b o xy I i c acid, isonicotinic acid, 3-pyridinepropionic acid, 4-hydroxyphenylacetic acid, 2-butynoic acid, 2-pyrazinecarboxylic acid, cyclopropanecarboxylic acid, 3-hydroxy-2-qui-noxaline carboxylic acid, 5-bromovaleric acid, propargyl chloroformate, 3,4-dimethoxybenzoyl chloride, 2-thiophenesulfonyl chloride, 3-thiophene-carboxylic acid, 2-thiophenecarboxylic acid, 2-methylbutyric acid, 2-thio-pheneacetyl chloride, benzoic acid, furylacrylic acid, 4-nitrophenyl acetic acid, 2,5-dimethoxyphenylacetic acid, p-toluenesulfonyl chloride, 4-(di-methylamino)phenylacetic acid, 3-indolepropionic acid, phenoxyacetic acid, 3-(dimethylamino)benzoic acid, cyclohexanecarboxylic acid, naphtha-lenesulfonyl chloride, 4-bromophenylacetic acid, 4-bromobenzoic acid, 2-phenoxybutyric acid, 3,4-dichlorophenylacetic acid, (l-naphthoxy)acetic acid. 

Many organic compounds react with carboxylic acids, acyl halides, or anhydrides in the presence of certain metallic halides, metallic oxides, iodine, or inorganic acids to form carbonyl compounds. The reaction is generally applicable to aromatic hydrocarbons. Benzene, alkylbenzenes, biphenyl, fluorene, naphthalene, anthracene, acenaphthene, phenanthrene, higher aromatic ring systems, and many derivatives undergo the reaction. 

Aldehyde Ketone Carboxylic acid Acyl chloride Ester... 

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