Carboxylic acid fluorides chlorides

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 ... 

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... 

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. °... 

Carboxylic acid fluorides are more stable to water and other nucleophiles. They are readily prepared by the use of cyanuric fluoride and converted to amides by siiylated amines. In contrast to the chlorides, protected amino acid fluorides exert virtually no racemization in peptide coupling. ... 

Sulfonyl fluorides are readily obtained from sulfonyl chlorides and KF or KHF2j even in an aqueous medium.801"804 Carboxylic acid fluorides are formed when the acid chlorides are heated with dry KF and can be removed continuously from the reaction mixture by distillation through a column formyl and acetyl fluorides are thus obtained when the acid is heated with benzoyl chloride and KF.805,806 Xylene or acetamide may be used as diluent. Further, a>chloro and at-bromo fatty esters, nitriles, and amides react with KF at temperatures around 100-150°. 

Carboxylic acid fluorides are not of particular preparative importance since the reactions that can be carried out with them proceed analogously with the cheaper carboxylic acid chlorides. These fluorides are very stable, even towards hydrolysis. Formyl fluoride can be kept at room temperature for several hours before it decomposes into CO and HF. The preparation of carboxylic acid fluorides from the corresponding chlorides and KF was mentioned on page 204. If butyric anhydride is heated gradually to 180° with KHF2, butyryl fluoride, b.p. 67° 1167 mm, distils off, and benzoyl fluoride, b.p. 155-156°, can be obtained analogously from benzoic anhydride at 190-240°. KF can also be used in place of KHF2. Yields are around 80-90%.1079... 

Electrochemical fluorination of carboxylic acid fluoride and chloride or alkylsulphonic acid fluoride/ chloride is carried out in anhydrous hydrofluoric acid medium at t < 19 C (or t<35°C for n-C8Hi5S02F) at a voltage of 5-12 V and electric current density of 0.02 A/m ... 

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

Carboxylic acid fluorides can be prepared from the free acids by treatment with hexafluoro-1,2-epoxypropane, and benzylidene chlorides are converted into the... 

The electrochemical fluorination of the corresponding hydrocarbon carboxylic acid fluorides or chlorides follows the general reaction scheme ... 

SO3 added during 10 min. with occasional cooling at 30-40° under dry Ng to stirred benzoyl chloride, and allowed to stand 1 hr. benzoyl chlorosulfate. Y 99%. F. e., also insertion into carboxylic acid fluorides and esters, s. C. G. Krespan and D. C. England, J. Org. Chem. 40, 2937 (1975). 

The carboxylic acid fluorides are soluble in HF, and the solutions of alkanoic acid fluorides with more than four carbon atoms are conductive. The yield of the perfluoroalkanoic acid fluoride decreases with increasing chain length of the carboxylic acid fluoride fluorinated, from as much as about 80% for acetyl fluoride to 10% for perfluorooctanoyl fluoride [34]. The yield is lower when an acyl chloride is fluorinated instead of an acyl fluoride, but aeyl chlorides are more readily available than acyl fluorides [48]. 

During electrochemical fluorination retention of important functional groups or atoms in molecules is essential. Acyl fluorides and chlorides, but not carboxylic acids and anhydrides (which decarboxylate), survive perfluorination to the perfluorinated acid fluorides, albeit with some cyclization in longer chain (>C4) species [73]. Electrochemical fluorination of acetyl fluoride produces perfluoro-acetyl fluoride in 36-45% yields [85]. Electrochemical fluorination of octanoyl chloride results in perfluorinated cyclic ethers as well as perfluorinated octanoyl fluonde. Cyclization decreases as initial substrate concentration increases and has been linked to hydrogen-bonded onium polycations [73]. Cyclization is a common phenomenon involving longer (>C4) and branched chains. a-Alkyl-substituted carboxylic acid chlorides, fluorides, and methyl esters produce both the perfluorinated cyclic five- and six-membered ring ethers as well as the perfluorinated acid... 

Theperfluoroorganozmc compounds have limited application in organic syn thesis because of their lack of reactivity However, heptafluoro I methylethylzinc iodide reacts with acyl fluorides or anhydrides of carboxylic acids in the presence of pyndine to give the corresponding ketones [7S] (equations 28 and 29) In the presence of zinc fluoride, acyl chlorides can be used as substrates [7d]... 

The next major obstacle is the successful deprotection of the fully protected palytoxin carboxylic acid. With 42 protected functional groups and eight different protecting devices, this task is by no means trivial. After much experimentation, the following sequence and conditions proved successful in liberating palytoxin carboxylic acid 32 from its progenitor 31 (see Scheme 10) (a) treatment with excess 2,3-dichloro-5,6-dicyano-l,4-benzoquinone (DDQ) in ie/t-butanol/methylene chloride/phosphate buffer pH 7.0 (1 8 1) under sonication conditions, followed by peracetylation (for convenience of isolation) (b) exposure to perchloric acid in aqueous tetrahydrofuran for eight days (c) reaction with dilute lithium hydroxide in H20-MeOH-THF (1 2 8) (d) treatment with tetra-n-butylammonium fluoride (TBAF) in tetrahydrofuran first, and then in THF-DMF and (e) exposure to dilute acetic acid in water (1 350) at 22 °C. The overall yield for the deprotection sequence (31 —>32) is ca. 35 %. 

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]. 

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