Acyl halides, from acids

Formation of Acyl Halides from Acid Derivatives... 

Formation of Acyl Halides from Acid Derivatives Halo-de-acyloxy-substitution Halo-de-halogenation... 

The formation of acyl halide-Lewis acid complexes have been observed by several methods. For example, both 1 1 and 1 2 complexes of acetyl chloride, with AICI3 can be observed by NMR spectroscopy. The existence of acylium ions has been demonstrated by X-ray diffraction studies on crystalline salts. For example, crystal structure determinations have been reported for /i-methylphenylacylium and acetylium ions as SbFg salts. There is also a good deal of evidence from NMR measurements which demonstrates that acylium ions can exist in nonnucleophilic solvents. " The positive charge on acylium ions is delocalized onto the oxygen atom. This delocalization is demonstrated in particular by the short O—C bond lengths in acylium ions, which imply a major contribution from the structure having a triple bond ... 

The A-(l-acyloxyalkyl)amides or carbamates arc easily prepared from the corresponding hydroxy compounds by conventional acylation methods, such as heating with the required carboxylic acid in the presence of a strong acid or treatment with acyl halides or acid anhydrides1. 

In addition to acyl halides and acid anhydrides, there are a number of milder and more selective acylating agents that can be readily prepared from carboxylic acids. Imidazolides, the (V-acyl derivatives of imidazole, are examples.115 Imidazolides are isolable substances and can be prepared directly from the carboxylic acid by reaction with carbonyldiimidazole. 

The polymer-supported superbase 30 was developed and used for the deprotonation and alkylation of weakly acidic nitrogen heterocycles such as indoles, phthalazinones, and pyrazoles.46 The diagram below illustrates the use of superbase 30 to alkylate a weakly basic pyrazole NH after acylation or alkylation of the more nucleophilic piperidine NH. Ami-nomethyl resin 1 was added after each step to sequester excess alkyl and/or acyl halide from the solution phase. 

The primary and secondary alcohol functionalities have different reactivities, as exemplified by the slower reaction rate for secondary hydroxyls in the formation of esters from acids and alcohols (8). 1,2-Propylene glycol undeigoes most of the typical alcohol reactions, such as reaction with a free acid, acyl halide, or acid anhydride to form an ester reaction with alkali metal hydroxide to form metal salts and reaction with aldehydes or ketones to form acetals and ketals (9,10). The most important commercial application of propylene glycol is in the manufacture of polyesters by reaction with a dibasic or polybasic acid. 

In this procedure no ptossibility of the formation of water exists at any stage of the reaction. The method has been used for the preparation of several a, olefinic acyl halides from phosphorus oxychloride, although the procedure is said to be less satisfactory than treatment of the free acid with phosphorus trichloride (method 335). ... 

The electrophile is the acylium ion, R-C +, generated by Lewis acid-catalyzed ionization of a leaving group (path Dn) from acyl halides or acid anhydrides (shown in the previous section). The proton that is lost comes from the same carbon that the electrophile attacked. The reaction fails for deactivated rings (Ai wg, meta directors). After the electrophile adds it deactivates the ring toward further attack. No rearrangement of the electrophile occurs. 

Monoacylation of 2,3-diaminoquinoxalines has been achieved by reaction with an acid anhydride in THF. Under more vigorous conditions reaction of 2,3-diaminoquinoxalines with acid anhydrides results in ring closure to an imidazo[ ]quinoxaline. Similar ring closures have been carried out with aldehydes, acyl halides, formic acid, orthoesters, and urea. Polycyclic compounds have also been prepared from 2,3-diaminoquinoxaline by reaction with 1,-2-dicarbonyl compounds and 1,2-diamines, as illustrated in Scheme 7. 

The derivatives of three classes of compounds (carboxylic acids, acyl halides and acid anhydrides) are essentially the same as those of carboxylic acids, and are prepared either directly from the acid or vta the acyl halide All of them appear therefore under the same title... 

The liquid phosphorus oxychloride, b.p. 107°, is a by-product and is removed by fractional distillation under normal pressure. Unless the b.p. of the acid chloride differs very considerably (say, <] 100°) from that of the phosphorus oxychloride, the acyl halide is liable to contain traces of the latter. In such circumstances it is preferable to use thionyl chloride for the preparation of the acid chloride. 

The acylpalladium complex formed from acyl halides undergoes intramolecular alkene insertion. 2,5-Hexadienoyl chloride (894) is converted into phenol in its attempted Rosenmund reduction[759]. The reaction is explained by the oxidative addition, intramolecular alkene insertion to generate 895, and / -elimination. Chloroformate will be a useful compound for the preparation of a, /3-unsaturated esters if its oxidative addition and alkene insertion are possible. An intramolecular version is known, namely homoallylic chloroformates are converted into a-methylene-7-butyrolactones in moderate yields[760]. As another example, the homoallylic chloroformamide 896 is converted into the q-methylene- -butyrolactams 897 and 898[761]. An intermolecular version of alkene insertion into acyl chlorides is known only with bridgehead acid chlorides. Adamantanecarbonyl chloride (899) reacts with acrylonitrile to give the unsaturated ketone 900[762],... 

Carboxylic acid hydiazides are prepared from aqueous hydrazine and tfie carboxylic acid, ester, amide, anhydride, or halide. The reaction usually goes poody with the free acid. Esters are generally satisfactory. Acyl halides are particularly reactive, even at room temperature, and form the diacyl derivatives (22), which easily undergo thermal dehydration to 1,3,4-oxadiazoles (23). Diesters give dihydtazides (24) and polyesters such as polyacrylates yield a polyhydrazide (25). The chemistry of carboxyhc hydrazides has been reviewed (83,84). 

Codeposition of silver vapor with perfluoroalkyl iodides at -196 °C provides an alternative route to nonsolvated primary perfluoroalkylsilvers [272] Phosphine complexes of trifluaromethylsilver are formed from the reaction of trimethyl-phosphme, silver acetate, and bis(trifluoromethyl)cadmium glyme [755] The per-fluoroalkylsilver compounds react with halogens [270], carbon dioxide [274], allyl halides [270, 274], mineral acids and water [275], and nitrosyl chloride [276] to give the expected products Oxidation with dioxygen gives ketones [270] or acyl halides [270] Sulfur reacts via insertion of sulfur into the carbon-silver bond [270] (equation 188)... 

The formulated mechanism is supported by the finding that no halogen from the phosphorus trihalide is transferred to the a-carbon of the carboxylic acid. For instance, the reaction of a carboxylic acid with phosphorus tribromide and chlorine yields exclusively an a-chlorinated carboxylic acid. In addition, carboxylic acid derivatives that enolize easily—e.g. acyl halides and anhydrides—do react without a catalyst present. 

Unsymmetrical as well as symmetrical anhydrides are often prepared by the treatment of an acyl halide with a carboxylic acid salt. The compound C0CI2 has been used as a catalyst. If a metallic salt is used, Na , K , or Ag are the most common cations, but more often pyridine or another tertiary amine is added to the free acid and the salt thus formed is treated with the acyl halide. Mixed formic anhydrides are prepared from sodium formate and an aryl halide, by use of a solid-phase copolymer of pyridine-l-oxide. Symmetrical anhydrides can be prepared by reaction of the acyl halide with aqueous NaOH or NaHCOa under phase-transfer conditions, or with sodium bicarbonate with ultrasound. 

These reactions are most important for the preparation of acyl fluorides. " Acyl chlorides and anhydrides can be converted to acyl fluorides by treatment with polyhydrogen fluoride-pyridine solution" or with liquid HF at — 10°C. Formyl fluoride, which is a stable compound, was prepared by the latter procedure from the mixed anhydride of formic and acetic acids. Acyl fluorides can also be obtained by reaction of acyl chlorides with KF in acetic acid or with DAST. Carboxylic esters and anhydrides can be converted to acyl halides other than fluorides by the inorganic acid halides mentioned in 10-77, as well as with PhsPXa (X = Cl or but this is seldom done. Halide exchange can be carried out in a... 

Aldehydes have been prepared from carboxylic acids or acyl halides by first converting them to certain types of amides that are easily reducible. The following are some examples ... 

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