Acid halides reactivity

Mote stable catalysts ate obtained by using fluorinated graphite or fluorinated alumina as backbones, and Lewis acid halides, such as SbF, TaF, and NbF, which have a relatively low vapor pressure. These Lewis acids ate attached to the fluorinated soHd supports through fluorine bridging. They show high reactivity in Friedel-Crafts type reactions including the isomerization of straight-chain alkanes such as / -hexane. 

Acid halides are among the most reactive of carboxylic acid derivatives and can be converted into many other kinds of compounds by nucleophilic acyl substitution mechanisms. The halogen can be replaced by -OH to yield an acid, by —OCOR to yield an anhydride, by -OR to yield an ester, or by -NH2 to yield an amide. In addition, the reduction of an acid halide yields a primary alcohol, and reaction with a Grignard reagent yields a tertiary alcohol. Although the reactions we ll be discussing in this section are illustrated only for acid chlorides, similar processes take place with other acid halides. 

The reactivity of an acid derivative toward substitution depends both on the steric environment near the carbonyl group and on the electronic nature of the substituent, Y. The reactivity order is acid halide > acid anhydride > thioester > ester > amide. 

Compared with esters, acid halides and anhydrides are more reactive and are hydrolyzed more readily. It is interesting to note that there is a substantial lifetime for these acid derivatives in aqueous media. Acid halides dissolved in PhCl or in PhBr shaken at a constant rate with water shows that hydrolysis occurs at the boundary between the two liquid phases.35 The reaction of benzoyl chloride (PhCOCl) and benzoate ion with pyridine A-oxide (PNO) as the inverse phase-transfer catalyst yields both the substitution product (benzoic anhydride) and the... 

Catalytic amounts of I fCl4-AgC104 and Hf(OTf)4 are used for activation of acid halides and acid anhydrides for Friedel -Crafts acylation (Scheme 42) 178 the reactions of both reactive and unreactive aromatic substrates proceed smoothly in the presence of Hf(OTf)4. Furthermore, the Fries rearrangement179,180 and direct C-acylation of phenolic compounds181,182 take place using Hf(OTf)4. Formation of esters and Mannich-type reactions and allylation of imines have been also reported.152... 

Even though sulfuryl chloride and sulfuryl fluoride can be considered as the disubstituted acid halides of sulfuric acid, the monosubstituted derivatives are also useful compounds that undergo many reactions a result of the reactive -OH group. The monosubstituted compounds can be prepared by the following reactions ... 

Analysis of the relative yields of products in these reactions suggests that the order of reactivity towards acid halides in pyridine... 

Acid halides RCOX NA Generally insoluble, very reactive... 

The most frequently used method for the preparation of isoquinoline Reissert compounds is treatment of an isoquinoline with acyl chloride and potassium cyanide in water or in a dichloromethane-water solvent system. Though this method could be successfully applied in a great number of syntheses, it has also some disadvantages. First, the starting isoquinoline and the Reissert compound formed in the reaction are usually insoluble in water. Second, in the case of reactive acyl halides the hydrolysis of this reaction partner may became dominant. Third, the hydroxide ion present could compete with the cyanide ion as a nucleophile to produce a pseudobase instead of Reissert compound. To decrease the pseudobase formation phase-transfer catalysts have been used successfully in the case of the dichloromethane-water solvent system, resulting in considerably increased yields of the Reissert compound. To avoid the hydrolysis of reactive acid halides in some cases nonaqueous media have been applied, e.g., acetonitrile, acetone, dioxane, benzene, while utilizing hydrogen cyanide or trimethylsilyl cyanide as reactants instead of potassium cyanide. 

Acid halides and anhydrides are so reactive that they react with water under neutral conditions. This can he a potential problem for the storage if these compounds since these compounds can he air (moisture) sensitive. Hydrolysis of these compounds can he avoided hy using dry nitrogen atmospheres and anhydrous solvents and reagents. 

When maltose was treated with 8 molar equivalents of benzoyl chloride in pyridine at —40°, it afforded octa-0-benzoyl-/3-maltose, l,2,6,2, 3, 4, 6 -hepta-0-benzoyl-/3-maltose, and l,2,6,2, 3, 6 -hexa-0-benzoyl-/3-maltose in yields of 3, 79, and 12%, respectively.69 Similar treatment of methyl /3-maltoside with 7 molar proportions of benzoyl chloride in pyridine gave crystalline methyl 2,6,2, 3, 4, 6 -hexa-0-benzoyl -/3 - maltoside and methyl 2,6,2, 3, 6 -penta-O -benzoyl -/3 -maltoside in yields of 71 and 23%, respectively.69 Analysis of the relative yields of the products of these reactions suggests that, after HO-3, the 4 -hydroxyl group in maltose and methyl /3-maltoside is the most hindered. Benzoylation of methyl 4, 6 -0-benzylidene-/3-maltoside with 10 molar proportions of reagent gave 2,6,2, 3 -tetra-0-benzoyl-4, 6 -0-benzylidene-/3-maltoside (71%) and an equimolar mixture (22%) of the 2,6,2 - and 2,6,3 -tribenzoates. These results indicated that the order of reactivity of the hydroxyl groups towards acid halides in pyridine is HO-2, HO-6 > HO-2 HO-3 > HO-3. 

The conversion of carboxylic acids into corresponding acid halides (COF or COC1) involves an increase of the reactivity of organic acids and can authorize subsequent reactions not easy to perform in soft conditions with the parent acid. For example, amides and esters can be quantatively obtained by treatment of acid halide derivatives by ammonia and methanol vapor respectively ... 

Treatment of polymer films by reactive gases or reactive volatil compounds allows to easily modify polymers containing alcohols, hydroperoxides, carboxylic acids (or acids halides), double bonds or piperidine groups. New functional groups as organic nitrites, nitrates, iodides, acid halides (Cl, F), amides, esters, peresters and nitroxyl radicals can be generated by a single reaction or by combination of two consecutive treatments. The reactions are very efficient on thin films (ca 50-100 pm) and can be controlled by transmission and reflexion 1R spectroscopy. 

In contrast to the inertness of carbon halides, the halides of silicon and phosphorus are extremely reactive with water, to the extent that they must be protected from atmospheric moisture. A clue to the reactivity of these halides is provided hy the somewhat Similar reactivity of acid halides which readily react with water... 

Often the requisite THF oxonium ion is generated in situ by using a combination of reagents based on the Meerwein syntheses of trialkyl oxonium salts (150). These combinations include epichlorohydrin or a reactive halide with a Lewis acid, a reactive halide with a metal salt, or sometimes just a Lewis acid alone. The epoxide portion is often referred to as a promoter. 

Amides may be made in a number of ways. Prominent among them is the acylation of amines. The agents commonly used are, in order of reactivity, the acid halides, acid anhydrides, and esters. Such reactions are ... 

Nickel tetracarbonyl is known to dissociate into the more reactive tricarbonyl readily [step (1)] and this species is known to react readily with a variety of halides by oxidative addition presumably as shown in steps (2) and (3). Subsequent loss of CO would give an equilibrium mixture of the four complexes shown in (3). Step (4) is the well-known carbon monoxide insertion reaction. The acylnickel complex formed in this step then may re-ductively eliminate acid halide [step (5)], which then alcoholizes [step (6)] or it may react directly with alcohol to form ester and a hydridonickel complex (7), which then reacts with CO and decomposes to nickel tricarbonyl and HC1 (8) ... 

Ketene Insertions. Ketenes insert into strongly polarized or polarizable single bonds, such as reactive carbon-halogen bonds, giving acid halides (7) and into active acid halides giving halides of P-ketoacids (8) (46). Phosgene [77 14-5] (47) and thiophosgene [463-71-8] (48) also react with ketenes. 

Carboxylic acid chlorides and chloroformate esters add to tetrakis(triphenylphosphine)palladium(0) to form acylpalladium derivatives (equation 42).102 On heating, the acylpalladium complexes can lose carbon monoxide (reversibly). Attempts to employ acid halides in vinylic acylations, therefore, often result in obtaining decarbonylated products (see below). However, there are some exceptions. Acylation may occur when the alkenes are highly reactive and/or in cases where the acylpalladium complexes are resistant to decarbonylation and in situations where intramolecular reactions can form five-membered rings. 

Another interesting facet of Pd(0) oxidative insertion is the chemoselectivity of the process. The most reactive bonds are vinyl and aryl C-X bonds, whereas with most other metals these are the least reactive bond types. Palladium(O) also inserts into allylic halides and esters, acid halides, and several other bonds but reacts only sluggishly with C-X bonds to saturated carbon. Taken together these characteristics make Pd(0) chemistry nearly unique. 

Reactions of acid halides (acyl halides). Acyl halides are very reactive and easily converted to esters, anhydrides, amides, N-substituted amides, and carboxylic acids. In the following reactions, X represents any halide. 

Halonium ions are an important class of onium ions.43 The dialkylchloro, bromo, and iodohalonium ions can be prepared and even isolated as stable salts (i.e., 46), as shown by Olah et al. by reacting an excess of haloalkane with strong Lewis acid halides in solvents of low nucleophilic-ity (eq 14). In superacid solution, dialkylhalonium ions show enhanced alkylating reactivity.44 It is considered that this enhanced reactivity is due to further protolytic (or electrophilic) activation involving the non-bonded... 

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