Acid anhydrides reactivity

The choice of type of derivative should be based on whether the chloride or anhydride is aliphatic or aromatic, because this factoi largely determines the reactivity. Aliphatic acid chlorides are best converted into their anilides, as in 4 above aromatic acid chloride may be similarly converted into their anilides, or they may be converted into their amides by shaking with an excess of ammonia (p, 120). (M.ps., pp. 544-545.) Aliphatic acid anhydrides should be converted into their crystalline anilides, but aromatic acid anhydrides arc best hydrolysed to the acid, which can then be converted into one of the standard derivatives (p. 349). 

Acyl cations (acylium ions) generated by treating an acyl chloride or acid anhydride with aluminum chloride attack aromatic rings to yield ketones The arene must be at least as reactive as a halobenzene Acyl cations are relatively stable and do not re arrange... 

The mechanisms of the Fischer esterification and the reactions of alcohols with acyl chlorides and acid anhydrides will be discussed m detail m Chapters 19 and 20 after some fundamental principles of carbonyl group reactivity have been developed For the present it is sufficient to point out that most of the reactions that convert alcohols to esters leave the C—O bond of the alcohol intact... 

The chemistry of the carbonyl group is probably the single most important aspect of organic chemical reactivity Classes of compounds that contain the carbonyl group include many derived from carboxylic acids (acyl chlorides acid anhydrides esters and amides) as well as the two related classes discussed m this chapter aldehydes and ketones... 

Esters Like acid anhydrides the carbonyl group of an ester is stabilized by elec tron release from oxygen Because there is only one carbonyl group versus two m anhydrides esters are stabilized more and are less reactive than anhydrides... 

After acyl halides acid anhydrides are the most reactive carboxylic acid derivatives Three of them acetic anhydride phthahc anhydride and maleic anhydride are mdus trial chemicals and are encountered far more often than others Phthahc anhydride and maleic anhydride have their anhydride function incorporated into a nng and are referred to as cyclic anhydrides... 

Acid anhydrides are more stable and less reactive than acyl chlorides Acetyl chlo ride for example undergoes hydrolysis about 100 000 times more rapidly than acetic anhydride at 25°C... 

Nucleophilic acyl substitutions at the ester carbonyl group are summarized m Table 20 5 on page 849 Esters are less reactive than acyl chlorides and acid anhydrides Nude ophilic acyl substitution m esters especially ester hydrolysis has been extensively mves tigated from a mechanistic perspective Indeed much of what we know concerning the general topic of nucleophilic acyl substitution comes from studies carried out on esters The following sections describe those mechanistic studies... 

Section 20 6 Acid anhydrides are less reactive toward nucleophilic acyl substitution than acyl chlorides but are useful reagents for preparing esters and amides... 

Amines are convert ed to amides on reaction with acyl chlorides Other acylating agents such as carboxylic acid anhydrides and esters may also be used but are less reactive... 

A series of water-soluble fiber-reactive xanthene dyes has been prepared from the reaction of ben2oxanthenedicatboxylic acid anhydride disulfonic acid with, for example, 3-aminophenyl-P-hydtoxyethyl sulfone to yield dyes, with high brilliance and good fastness properties for dyeing of or printing on leather, wool, sHk, or ceUulosic fibers (53). 

The primary and secondary alcohol functionahties 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 undergoes most of the typical alcohol reactions, such as reaction with a free acid, acyl hahde, or acid anhydride to form an ester reaction with alkaU metal hydroxide to form metal salts and reaction with aldehydes or ketones to form acetals and ketals (9,10). The most important commercial appHcation of propylene glycol is in the manufacture of polyesters by reaction with a dibasic or polybasic acid. 

Liquid crystal polyesters are made by a different route. Because they are phenoHc esters, they cannot be made by direct ester exchange between a diphenol and a lower dialkyl ester due to unfavorable reactivities. The usual method is the so-called reverse ester exchange or acidolysis reaction (96) where the phenoHc hydroxyl groups are acylated with a lower aHphatic acid anhydride, eg, acetic or propionic anhydride, and the acetate or propionate ester is heated with an aromatic dicarboxyHc acid, sometimes in the presence of a catalyst. The phenoHc polyester forms readily as the volatile lower acid distills from the reaction mixture. Many Hquid crystal polymers are derived formally from hydroxyacids (97,98) and thein acetates readily undergo self-condensation in the melt, stoichiometric balance being automatically obtained. 

The acid chlorides are generally more reactive than the corresponding acid anhydrides. In fact, the alcoholysis of acid chlorides is probably the best laboratory method for preparing esters. Frequentiy, basic materials are added during the course of the reaction to neutralize by-product hydrochloric acid. When the basic material is aqueous caustic, the procedure is referred to as the Schotten-Baumann procedure (73). Esterification of tertiary alcohols by acid chlorides is described in Reference 74. Esters of tertiary alcohols can also be formed through an intermediate /-butyl thioate group (75) ... 

Furan can also be acylated by the Vilsmeier-Haack method. Acylation of furans can also be carried out with acid anhydrides and acyl halides in the presence of Friedel-Crafts catalysts (BF3-Et20, SnCU or H3PO4). Reactive anhydrides such as trifluoroacetic anhydride, however, require no catalyst. Acetylation with acetyl p-toluenesulfonate gives high yields. 

By virtue of their fused /3-lactam-thiazolidine ring structure, the penicillins behave as acylating agents of a reactivity comparable to carboxylic acid anhydrides (see Section 5.11.2.1). This reactivity is responsible for many of the properties of the penicillins, e.g. difficult isolation due to hydrolytic instability (B-49MI51102), antibacterial activity due to irreversible transpeptidase inhibition (Section 5.11.5.1), and antigen formation via reaction with protein molecules. 

The epoxidised polybutadiene resins available to date are more viscous than the diglycidyl ethers except where volatile diluents are employed. They are less reactive with amines but have a similar reactivity with acid anhydride hardeners. Cured resins have heat distortion temperatures substantially higher than the conventional amine-cured diglycidyl ether resins. A casting made from an epoxidised polybutadiene hardened with maleic anhydride and cured for two hours at 50°C plus three hours at 155°C plus 24 hours at 200°C gave a heat... 

As with the other non-glycidyl ether resins the absence of the ether oxygen near to the epoxide group results in low reactivity with amine hardemers whereas activity with acid anhydride proceeds at reasonable rates. 

In addition to the proteins discussed above, a large number of reactive chemicals used in industry can cause asthma and rhinitis. Hypersensitivity pneumonias have also been described. Isocyanates and acid anhydrides are industrial chemicals that cause occupational asthma. Acid anhydrides, such as phthalic anhydride, seem to cause mainly type I reactions, whereas the IgE-mediated mechanism explains only a part of the sensitizations to isocyanates. Several mechanisms have been suggested, but despite intensive research no models have been generally accepted. The situation is even more obscure for other sensitizing chemicals therefore, the term specific chemical hypersensitivity is often used for chemical allergies. This term should not be confused with multiple chemical sensitivity (MCS) syndrome, which is a controversial term referring to hypersusceptibility to very low levels of environmental chemicals. ... 

The use of acid chlorides instead of acid anhydrides has also been described. Wittig and coworkers converted propiophenone 31 to chromone 32 in 50% yield with chloroacetyl chloride in the presence of sodium chloroacetate at 190 C. Despite the acid chloride s increased reactivity, a high temperature was still required. 

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. 

We ve already studied the two most general reactions of amines—alkylation and acylation. As we saw earlier in this chapter, primary, secondary, and tertiary amines can be alkylated by reaction with a primary alkyl halide. Alkylations of primary and secondary amines are difficult to control and often give mixtures of products, but tertiary amines are cleanly alkylated to give quaternary ammonium salts. Primary and secondary (but not tertiary) amines can also be acylated by nucleophilic acyl substitution reaction with an acid chloride or an acid anhydride to yield an amide (Sections 21.4 and 21.5). Note that overacylation of the nitrogen does not occur because the amide product is much less nucleophilic and less reactive than the starting amine. 

Cyclic acid anhydrides are highly reactive not only to electrophilic attack but also to nucleophilic attack. Alternating copolyesters were obtained from cyclic acid anhydrides and epoxides at high temperatures261-263. ... 

Recently, use of LiCl/DMAc and LiCl/l,3-dimethyl-2-imidazolidinone as solvent systems for acetylation of cellulose by acetic anhydride/pyridine has been compared. A DS of 1.4 was obtained the substituent distribution in the products synthesized in both solvents was found to be the same, with reactivity order Ce > C2 > C3. Therefore, the latter solvent system does not appear to be better than the much less expensive LiCl/DMAc, at least for this reaction. It appears, however, to be especially efficient for etherification reactions [178]. It is possible, however, that the effect of cellulose aggregation is more important for its reaction with the (less reactive) halides than with acid anhydrides this being the reason for the better performance of the latter solvent system in ether formation, since it is more efficient in cellulose dissolution. 

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