Acylating agents carboxyl compounds

Those polyester FBAs containing a benzoxazole group are usually prepared from the appropriate o-aminophenol and carboxylic acid (11.45 Y = OH) or one of its derivatives, as shown in Scheme 11.10. The reaction proceeds via an intermediate amide and it can be advantageous to start from an acid derivative such as the acid chloride (11.45 Y = Cl) or ester (11.45 Y = OEt), which are both more effective acylating agents. The preparation of compound 11.36, shown in Scheme 11.11, illustrates this process, but the optimum conditions for ring closure vary considerably from one structure to another. The article by Gold contains a valuable and detailed summary [4]. 

A wide range of A-acylbenzotriazoles 915 have been prepared under mild conditions in reactions of carboxylic acids with thionyl chloride in the presence of fourfold excess of benzotriazole, including R = alkyl, a-haloalkyl, a-alkoxyalkyl, alkenyl, alkinyl, aryl, and heteroaryl <2003S2795, 2004RQM275>. They represent convenient acylating agents for variety of nucleophiles. Synthetic applications of such compounds have been reviewed <2005SL1656>. 

Amino groups react very easily with aldehydes or ketones, and with aldehydes in the presence of amines, they can be acylated by the usual acylating agents, and they react with amidacetals, Vilsmeier reagents and nitroso compounds (Scheme 12). As mentioned earlier, alkylation leads mainly to AT(2)-alkylated products. The hydrazino group reacts in the same way as the amino group with aldehydes or ketones, with acyl chlorides or carboxylic anhydrides, with sulfonyl chlorides, ortho esters, carbon disulfide and with nitrous acid. The last three reactions have mainly been used for the synthesis of condensed 1,2,4-triazines. 

Support-bound phenols, oximes, and related compounds yield, upon acylation, esters that are highly susceptible to nucleophilic cleavage. These esters are often used as insoluble acylating agents for the preparation of amides or esters, but only occasionally as linkers for carboxylic acids [113]. These linkers are considered in Sections 3.3.3 and 3.5.1. 

Cs2.5 for the acylation. Anisole and /j-xylene are acylated with benzoic anhydride and acetic anhydride in the presence of Cs2.5 without the dissolution of this catalyst. Carboxylic acids are much less reactive as acylating agents than the corresponding anhydrides because of the liberation of water. But when the water is removed, the acylation proceeds smoothly 214). Although the reaction of benzene with acetic acid is attractive in prospect, there is no report of heteropoly compounds as catalysts for this reaction. 

Poor nucleophiles react with acyl isoureas B so slowly that the latter start to decompose. In some sense they acylate themselves. The N atom designated with the positional number 3 intramolecularly substitutes the O-bound leaving group that is attached to the carboxyl carbon Cl. A four-membered cyclic tetrahedral intermediate is formed. When the Cl -Ol bond in this intermediate opens up, the N-acyl urea E is produced. Because compound E is an amide derivative it is no longer an acylating agent (cf. Section 6.2). 

Most SN reactions of hydride donors, organometallic compounds, and heteroatom-stabi-lized carbanions at the carboxyl carbon follow the mechanism shown in Figure 6.2. Thus, the substitution products, i.e., the aldehydes and ketones C, form in the presence of the nucleophiles. Thus, when the nucleophile and the acylating agent are used in a 2 1 ratio, alcohols F are always produced. 

Fig. 6.40. On the chemo-selectivity of the reactions of hydride donors, organometallic compounds, and heteroatom-stabilized "carbanions with acylating agents (kM t refers to the rate constant of the addition of the nucleophile to the carboxyl carbon, and kadd2 refers to the rate constant of the addition of the nucleophile to the carbonyl carbon).

Most other carboxylic acid derivatives can acylate only ketone enolates that are formed quantitatively. In these reactions, the acylation product is a /J-diketone, i.e., an active-methylene compound. As a consequence it is so acidic that it will be deprotonated quantitatively. This deprotonation will be effected by the ketone enolate. Therefore, a complete acylation of this type can be achieved only if two equivalents of the ketone enolate are reacted with one equivalent of the acylating agent. Of course, proceeding in that manner would mean an unacceptable waste in the case of a valuable ketone. 

When carboxylic acids are treated with trifluoroacetic anhydride, mixed anhydrides (acyl trifluoroacetates) are formed. These compounds are useful acylating agents. What is the product of the reaction of an alcohol with acyl trifluoroacetate ... 

Sulfonic acids and carboxylic acids can be converted into their acid chlorides by treatment with phosphorus pentachloride or phosphorus oxychloride. Thionyl chloride, SOCl is effective for the synthesis of acyl chlorides, and sulfonyl chlorides can be prepared directly from the aromatic compound by reaction with an excess of chlorosulfonic acid. The acid chlorides are efficient Friedel-Crafts acylating agents, yielding sul-... 

Cyanuric chloride has been used for the preparation of acyl chlorides, amides, and peptides. Conversion of cyanuric chloride into 2-chloro-4,6-dimethoxy-l,3,5-triazine (CDMT, 6) leads to a reagent that upon reaction with carboxylic acids produces the highly reactive 2-acyloxy-4,6-dimethoxy-l,3,5-triazines.P l The resulting active ester is a powerful acylating agent for alcohols and amines. The activation is performed in presence of a base, preferentially NMM, which leads to intermediate formation of 4-(4,6-dimethoxy-l,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMTMM, 7)P l (Scheme 5). This addition product is readily prepared from the commercially available CDMT (6) and NMM in THF and can be stored as solid compound in the cold.P P l It offers the advantage that it can be used in a one-... 

The rate of acetylation of 0-(hydrox3Tnethyl)cellulose (and other hydroxy compounds) by mixtures of carboxylic acids and their anhydrides has been found to increase greatly in the presence of trifluoroacetic acid. The acceleration is very much less with mono- and tri-chloroacetic acids, presumably because they form unsymmetrical anhydrides which are less effective acylating agents than acyl trifluoroacetates. The exceptional acylating power of the latter anhydrides is shown by their use in the synthesis of alkyl aryl ketones from polyalkylbenzenes, phenyl ethers, furan, and thiophene under mild conditions. The principle has been extended to include acids... 

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