Functional derivatives acid chlorides

Ill spectroscopy is a valuable tool for the structural analysis of acid derivatives. Acid chlorides, anhydrides, esters, and amides all show characteristic IR absorptions that can be used to identify these functional groups. 

Acylimidazoles and Nucleophiles. Acylimidazoles are readily prepared from the parent carboxylic acids by reaction of the derived acid chloride with imidazole or directly using N,N -Carbonyldiimidazole. These intermediates react smoothly with a variety of nucleophiles including Grignard reagents (eq 3), Lithium Aluminum Hydride (eq 4), and nitronates (eq 5). At —20 ""C, aroylimidazoles can be reduced to the corresponding aldehydes in the presence of an ester function. ... 

Substitution at the Alcohol Group. Acylation of the OH group by acylating agents such as acid chlorides or anhydrides is one of the important high yielding substitution reactions at the OH group of lactic acid and its functional derivatives. AUphatic, aromatic, and other substituted derivatives can be produced. 

Alkyldithio carbamates are prepared from the acid chloride (Et N, EtOAc, 0°) and amino acid, either free or as the O-silyl derivatives (70-88% yield). The N- i-propyldithio) carbamate has been used in the protection of proline during peptide synthesis. Alkyldithio carbamates can be cleaved with thiols, NaOH, Ph P/TsOH. They are stable to acid. Cleavage rates are a function of the size of the alkyl group as illustrated in the table below. 

Replacement of the carbamate function by an amide seems to be compatible with meprobamate-like activity in a compound formally derived from a 1,2-glycol. Oxidation of the commercially available aldehyde, 22, under controlled conditions affords the corresponding acid (23). This is then converted to its amide (24) via the acid chloride. Epoxidation by means of perphthalic acid affords oxanamide (25). ... 

Latentiation of ampicillin can also be achieved by tying up the proximate amino and amide functions as an acetone aminal. Inclusion of acetone in the reaction mixture allows 6-APA to be condensed directly with the acid chloride from 24. There is thus obtained directly the prodrug hetacillin (34). Although this compound has little antibiotic activity in its own right, it hydrolyzes to ampicillin in the body. The p-hydroxy derivative amoxycillin (35) shows somewhat better oral activity. A similar sequence using formaldehyde gives metampicillin (36). °... 

The most important group of derivatives for the amino function (Fig. 7-4) is the carbamate group, which can be formed by reactions with acids, acid chlorides or acid anhydrides. A series of chlorides as 2-chloroisovalerylchloride [1], chrysanthe-moylchloride [2] and especially chloride compounds of terpene derivatives (cam-phanic acid chloride [3], camphor-10-sulfonyl chloride [4]) are used. The a-methoxy-a-trifluoromethylphenylacetic acid or the corresponding acid chloride introduced by Mosher in the 1970s are very useful reagents for the derivatization of amines and alcohols [5]. 

There are some problems associated with the use of functional derivatives of carboxylic acids. Long-chain acid anhydrides are not commercially available, and one half of the acylation reagent is not utilized. Acyl chlorides require the use of tertiary base catalysts, whose double role has been explained before. Some of the intermediate acyl ammonium compounds formed are, however, insoluble in the solvent system. Examples include RCO - N+EtsCL in LiCl/DMAc, where RCO refers to the propionyl, hexanoyl, and stearoyl moiety, respectively. Hexanoyl- and stearoyl-pyridinium chlorides are also insoluble in the same solvent system [185]. 

Suitable reagents for derivatizing specific functional groups are summarized in Table 8.21. Many of the reactions and reagents are the familiar ones used in qualitative analysis for the characterization of organic compounds by physical means. Alcohols are converted to esters by reaction with an acid chloride in the presence of a base catalyst (e.g., pyridine, tertiary amine, etc). If the alcohol is to be recovered after the separation, then a derivative which is fairly easy to hydrolyze, such as p-nltrophenylcarbonate, is convenient. If the sample contains labile groups, phenylurethane derivatives can be prepared under very mild reaction conditions. Alcohols in aqueous solution can be derivatized with 3,5-dinitrobenzoyl chloride. 

Two ways of linking the PEG molecules are (1) PEG derivatives are obtained by reacting the PEG polymer with a group that is reactive with hydroxyl groups, e.g., anhydride, acid chloride, chloroformate or carbonate and (2) attachment of functional groups such as aldehydes, esters, amides etc. with the PEG polymer. 

The chlorinated intermediate 255 is eliminated and cycloadds to Cjq, yielding pyrazo-linofullerenes of the structure 257 (Scheme 4.42). The 4-nitrophenyl-group can be replaced by a 4-methoxyphenyl- or a phenyl substituent. In this reaction various aromatics and substituted aromatics are tolerated as residues R (e.g. furan, ferrocene, pyrazole or benzene and substituted benzene). The nitro group of the nitrophenyl residue can be reduced with Sn-HCl to the aniline derivative, which can be further functionalized by amide coupling with acid chlorides [311]. 

Yet another piperidine-based antipsychotic agent replaces the butyrophenone or diarylpropyl function found in earlier compounds by a benzopyrimidine group. The synthesis starts by the conversion of the carboxylic acid in piperidine (22-1) to its acid chloride. Reaction with 1,3-difluorobenzene (22-2) in the presence of aluminum chloride affords the acylated product (22-3). Reaction with hydroxylamine leads to the corresponding oxime (22-4). Treatment of that derivative with a base... 

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