Carboxylic acid halides fluorides

Carboxylic acid fluorides, intermediates in the pathway to trifluoromethyl derivatives, are readily formed in reactions of all types of carboxylic acids with sulfur tetrafluoride derivatives (see Section 8.2.4.). Little attention has been paid to fluorination of other carboxylic acid halides. Aroyl chlorides are converted into aroyl fluorides by treatment with sulfur tetrafluoride, e.g. formation of l,41 or to (trifluoromethyl)arenes, e.g. 2 and 3. in the presence of hydrogen fluoride.45 Chlorination of the aromatic ring occurs in some cases.41... 

Carboxylic acid fluorides from carboxylic acid chlorides with formation of cyclopropanes from halides... 

Acid halides are named systematically by replacing the final ic acid of the carboxylic acid withy/halide. In practice, the names for the smaller acid halides are based upon the common names for the related acids. Thus, acetyl chloride and formyl fluoride would be understood everywhere. Formyl chloride is most unstable and efforts to make it under most conditions are rewarded only with the formation of HCl and CO. The diacid chloride of carbonic acid (Cl—CO—Cl) is known, however, and this deadly poison is called phosgene (Fig. 18.5). Throughout this... 

Notable examples of general synthetic procedures in Volume 47 include the synthesis of aromatic aldehydes (from dichloro-methyl methyl ether), aliphatic aldehydes (from alkyl halides and trimethylamine oxide and by oxidation of alcohols using dimethyl sulfoxide, dicyclohexylcarbodiimide, and pyridinum trifluoro-acetate the latter method is particularly useful since the conditions are so mild), carbethoxycycloalkanones (from sodium hydride, diethyl carbonate, and the cycloalkanone), m-dialkylbenzenes (from the />-isomer by isomerization with hydrogen fluoride and boron trifluoride), and the deamination of amines (by conversion to the nitrosoamide and thermolysis to the ester). Other general methods are represented by the synthesis of 1 J-difluoroolefins (from sodium chlorodifluoroacetate, triphenyl phosphine, and an aldehyde or ketone), the nitration of aromatic rings (with ni-tronium tetrafluoroborate), the reductive methylation of aromatic nitro compounds (with formaldehyde and hydrogen), the synthesis of dialkyl ketones (from carboxylic acids and iron powder), and the preparation of 1-substituted cyclopropanols (from the condensation of a 1,3-dichloro-2-propanol derivative and ethyl-... 

E-(P-Alkylvinyl)phenyliodonium salts react with tetra-n-butylammonium halides to yield the correspondingly substituted Z-haloethenes (80-100% for chloro-, bromo- and iodo-derivatives) [41], In contrast, in the corresponding reaction with Z-(2-benzenesulphonyl-ethenyl)phenyliodonium salts, nucleophilic substitution occurs with retention of configuration to yield the Z-2-benzenesulphonyl-l-haloethenes [42], The ammonium fluorides fail to yield the fluoroethenes, but produce the ethynes by simple elimination [41]. Where carboxylic acids have low solubility in organic solvents, their conversion into the acid chlorides is frequently difficult. Phase-transfer catalysis not only allows the conversion to be effected rapidly, it also results in high yields of a wide range of acid chlorides [43]. 

Tertiary benzylic nitriles are useful synthetic intermediates, and have been used for the preparation of amidines, lactones, primary amines, pyridines, aldehydes, carboxylic acids, and esters. The general synthetic pathway to this class of compounds relies on the displacement of an activated benzylic alcohol or benzylic halide with a cyanide source followed by double alkylation under basic conditions. For instance, 2-(2-methoxyphenyl)-2-methylpropionitrile has been prepared by methylation of (2-methoxyphenyl)acetonitrile using sodium amide and iodomethane. In the course of the preparation of a drug candidate, the submitters discovered that the nucleophilic aromatic substitution of aryl fluorides with the anion of a secondary nitrile is an effective method for the preparation of these compounds. The reaction was studied using isobutyronitrile and 2-fluoroanisole. The submitters first showed that KHMDS was the superior base for the process when carried out in either THF or toluene (Table I). For example, they found that the preparation of 2-(2-methoxyphenyl)-2-methylpropionitrile could be accomplished h... 

Monocationic acyl ions are readily prepared as persistent species in solutions of low nucleophile strength.68 These acyl ions have been thoroughly characterized by IR and NMR spectroscopy, and several acyl ion salts have been characterized by X-ray crystallography. The monocationic acyl ions are often prepared in situ from carboxylic acids, esters, or anhydrides, by the action of a strong Brpnsted acid, or the ions can be prepared from ionization of an appropriate acid halide with a strong Lewis acid. Both methods have been used to prepare acyl-centered dications, some of which can be considered distonic superelectrophiles. As described previously, dicarboxylic acids cleave to the bis-acyl ions in superacid (FSChH-SbFs) provided that the acyl cations are separated by at least three methylene units (eq 54).55 The first bis-acyl dications were reported by Olah and Comisarow, being prepared by the reactions of dicarboxylic acid fluorides with superacidic SbFs (eq 72).69... 

Transesterification has been carried out with phase-transfer catalysts, without an added solvent. Nonionic superbases (see p. 365) of the type P(RNCH2CH2)3N catalyze the transesterification of carboxylic acid esters at 25°C. ° Silyl esters (R C02SiR3) have been converted to alkyl esters (R C02R) via reaction with alkyl halides and tetrabutylammonium fluoride. Thioesters are converted to phenolic esters by treatment with triphosgene-pyridine and then phenol. 

The oxidation of primary alkyl halides to carboxylic acids is accomplished on incubation of long-chain aliphatic fluorides, chlorides, bromides, and iodides with the yeast Torulopsis gropengiesseri [1086,1087] (equation 200). The biooxidation starts at the terminal methyl groups and gives w-halogenoalkanoic acids, which are ultimately converted to a,oj-dicarboxylic... 

The thiolates, though less sensitive to basicity, are more reactive than oxygen anions over the total accessible range of basicity, but intersect the amine line at ca. pA 12. Other reactive nucleophiles which do not fall in the amine, thiolate, or oxygen anion categories are fluoride, thiosulfate, nitrite, azide, and sulfite. Halides other than fluoride, and also thiocyanate, nitrate, sulfate, and thiourea have no reactivity towards p-nitrophenyl acetate (Jencks and Carriuolo, 1960a). The total lack of reactivity of thiocyanate, iodide, bromide, and thiourea, all very polarizable nucleophiles which are reactive to sp carbon, rules out any possibility that polarizability is at all important in nucleophilic reactions at the carbonyl carbon. In general, the order of nucleophilic reactivity to p-nitrophenyl acetate correlates well with nucleophilic reactivity to other carboxylic acid derivatives (see later). Nitrite, however, shows... 

Acid anhydrides as activated derivatives of carboxylic acids have found little attention for the preparation of acid halides. Their use can be justified if they are obtained from other sources than from carboxylic acids, e.g. phthalic anhydride from the oxidation of naphthalene or o-xylene. It is, therefore, no surprise that there exist patents to convert phthalic anhydride to phthalic acid dichloride with carbonyl dichloride in the presence of catalysts. " However, there are some methods available thus a,a-di-chloromethyl methyl ether will convert acid anhydrides to acid chlorides and brenzcatechyl phosphorus tribromide will also achieve this transformation. Fluorides may be prepared similarly with the pyridine/HF mixture of 01ah. °... 

A general route to acid fluorides, chlorides, bromides and iodides is provided by the reaction of enol esters, such as isopropenyl esters, with the appropriate hydrogen halide (equation 18). Phthalic acid dichloride in the presence of chlorosulfonic acid has been proposed as a reagent for the conversion of carboxylic esters to acid chlorides in high yield, as is shown in equation (19) for the cleavage of the ethyl ester of chlorofluoroacetic acid. °... 

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