Active acylation

Appaiendy a molai equivalent of catalyst (AlCl ) combines with the acyl halide, giving a 1 1 addition compound, which then acts as the active acylating agent. Reaction with aromatics gives the AlCl complex of the product ketone hberating HX ... 

In these reactions the active acylating agent is the carbamyl chloride, formed by the reaction of the isocyanate with hydrogen chloride (137) ... 

Ca.rboxyhc Acids. Esters are the main products in the reaction of chloroformates with carboxyHc acids. The intermediate mixed carboxyhc—carbonic anhydrides are very active acylating agents (25—27) but these agents may be isolated in cold temperatures for producing useful products (28). 

Under more forcing conditions with acid anhydrides, EDA can form tetraacyl derivatives (29). However, much milder conditions or less active acylating agents are needed to obtain the monoamide essentially free of the diamide (30—32). 

The active acylating agent may be the protonated mixed anhydride, or, alternatively, the anhydride m dissociate to the acylium and trifluoroacetate ions ... 

The active acylating agent is presumably the C-protonated enol ester... 

AC2O or AcCl, Pyr, DMAP, 24-80°, 1-40 h, 72-95% yield. The use of DMAP increases the rate of acylation by a factor of lO. These conditions acylate most alcohols, including tertiary alcohols. The use of DMAP (4-A,A-dimethylaminopyridine) as a catalyst to improve the rate of esterification is quite general and works for other esters as well, but it is not effective with hindered anhydrides such as pivaloic anhydride. The phosphine i (48-99% yield) and Bu3P have been developed as active acylation catalysts for acetates and benzoates. 

Replacement of chlorine on the pendant benzoyl group by azide is apparently consistent with antiinflammatory activity. Acylation of indomethacin intermediate with p-nitrobenzoyl chloride leads to the corresponding amide (7). Saponification ( ) followed by reduction of the nitro group gives the amine 9. The diazonium salt (10) obtained on treatment with nitrous acid is then reacted with sodium azide there is thus obtained zidomethacin (11). 

Very few optically active cyanohydrins, derived from ketones, are described in the literature. High diastcrcosclectivity is observed for the substrate-controlled addition of hydrocyanic acid to 17-oxosteroids27 and for the addition of trimethyl(2-propenyl)silane to optically active acyl cyanides28. The enantioselective hydrolysis of racemic ketone cyanohydrin esters with yeast cells of Pichia miso occurs with only moderate chemical yields20. 

Figure 6.45 Activated acyl donors for irreversible acylation of alcohols.

Besides allylic substitution reactions it was also shown that [Fe(CO)3(NO)] 76 is catalytically active in transesterification reactions under neutral conditions (Scheme 24) [70]. Various activated acyl donors 97 can be used to give rise to the corresponding carboxylic esters 100 in good to excellent yields. This reaction proceeds in the absence of additional ligands in nonpolar solvents, for example, hexane. Mechanistically, the reaction is assumed to proceed via a Fe-acyl-complex 98 (Scheme 24). 

Hydroxyenones have also been used in catalytic amide formation, although 1,2,4-triazole is required as a co-catalyst. Assumed protonation of the Breslow intermediate and tautomerisation generates an acylazolium intermediate, which is trapped by triazole, releasing the NHC and generating the acyltriazole 60 that is the active acylating agent for the amine (Scheme 12.11) [16]. 

Scandium triflimidate, Sc[N(S02CF3)2]3, is also a very active acylation catalyst. 

Trimethylsilyl triflate is also a powerful catalyst for acylation by anhydrides. Reactions of alcohols with a modest excess (1.5 equival) of anhydride proceed in inert solvents at 0°C. Even tertiary alcohols react rapidly.114 The active acylation reagent is presumably generated by O-silylation of the anhydride. 

Scheme 3.4. Preparation and Reactions of Active Acylating Agents...

Friedel-Crafts acylation generally involves reaction of an acyl halide and Lewis acid such as A1C13, SbF5, or BF3. Bismuth(III) triflate is also a very active acylation catalyst.46 Acid anhydrides can also be used in some cases. For example, a combination... 

Determination of Optimal pH for SC-PEG Reactivity. To triethanolamine-borate buffer (0.3 M, 1 mL) at the appropriate pH, a stock solution of N,a-acetyl-lysine (NAL) in water (50 mM, 0.1 mL) was added followed by a stock solution of SC-activated mPEG-5000 in CH3CN (50 mM active acyl, 0.1 mL). The resultant solution was vortexed and incubated at 28 °C for 1 h. A mixture of the same components but leaving out SC-PEG was used as a control. The TNBS assay version of Snyder and Sobocinski (18) was used to determine the unreacted NAL. 

Acyl-coenzyme A compounds, which, because of their high acetyl group transfer potential represent carriers of activated acyl groups in biological systems, are prepared from the corresponding carboxylic acid, CDI, and coenzyme a.[4h5],[177],[182],[183]... 

In the presence of an active acyl donor such as isopropenyl acetate, a reductive acetylation of a ketone can be performed in the presence of MPVO catalysts... 

Scheme 3.4 gives some typical examples of preparation and use of active acylating... 

Bi(0Tf)3-xH20 proved to be a superior catalyst than BiCl3 for FC acylation (Schemes 7 and 8). Its activity as a Lewis acid is restricted to acid anhydrides since with acid chlorides Bi(0Tf)3-xH20 leads to ligand exchange reactions in which mixed anhydrides (RCOOTf, see path a in Scheme 8) are the active acylating... 

It therefore appeared that a general mechanism for enzymatic esterification of phenolic acids with glucose was operative, whereas the reaction with other alcoholic moieties proceeded via carboxyl-activated acyl derivatives. [In this context it should be emphasized that glucose esters must not be confused with glucosides different enzymes are involved in the biosynthesis of these two types of phenolic glucose derivatives (36)]. 

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