Acylation reagents

Substitutions. The cyanamide anion is strongly nucleophilic and reacts with most alkylating or acylating reagents (4) addition to a variety of unsaturated systems occurs readily (4). In some cases, a cyanamide salt is used in others, base catalysis suffices. Ethyl iodide reacts with sodium hydrogen cyanamide [17292-62-5] to form a trisubstituted isomelamine. 

Dihydropyrroles (2-pyrrolines 231) are in tautomeric equilibrium with the corresponding 1-pyrrolines (232) the latter readily form trimers of type (233). The trimer dissociates in boiling THF to 1-pyrroline (232) trimerization is relatively slow at -78 °C and the monomer can be trapped by reaction with acylating reagents to give (V-acyl-2-pyrrolines (81JOC4791). 

Ruonnated carboxylic anhydrides and acyl halides as common acylating reagents to convert amines to amides and to acy late suitable heterocyclic nitiogen atoms have already been described in the first edition [10] Like in the acylation at oxygen, much synthetic activity was concentrated m the past few years on the denvatization of biomolecules by fluoroacylation reactions, that is, tnfluoroacetylation of amino sugars,... 

There are some problems associated with the use of functional derivatives of carboxylic acids. Long-chain acid anhydrides are not commercially available, and one half of the acylation reagent is not utilized. Acyl chlorides require the use of tertiary base catalysts, whose double role has been explained before. Some of the intermediate acyl ammonium compounds formed are, however, insoluble in the solvent system. Examples include RCO - N+EtsCL in LiCl/DMAc, where RCO refers to the propionyl, hexanoyl, and stearoyl moiety, respectively. Hexanoyl- and stearoyl-pyridinium chlorides are also insoluble in the same solvent system [185]. 

Apart from being employed solely as solvents, ILs can also be used as reagent carriers (TSlLs, task-specific ionic liquids). An efficient system that uses ILs as solvents and anchoring/acylating reagents for the CAL B-catalyzed separation of racemic alcohols is shown in Scheme 5.17 [69]. 

Ketones are converted to (3-ketoesters by acylation with diethyl carbonate or diethyl oxalate, as illustrated by Entries 4 and 5 in Scheme 2.16. Alkyl cyanoformate can be used as the acylating reagent under conditions where a ketone enolate has been formed under kinetic control.227... 

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. 

Carboxylic acid esters of thiols are considerably more reactive as acylating reagents than the esters of alcohols. Particularly reactive are esters of pyridine-2-thiol because there is an additional driving force in the formation of the more stable pyridine-2-thione tautomer. 

In all these reactions, the acylating reagent reacts with the active Pd(0) catalyst to give an acyl Pd(II) intermediate. Transmetallation by the organoboron derivative and reductive elimination generate the ketone. 

Scheme 11.4 shows some other representative Friedel-Crafts acylation reactions. Entries 1 and 2 show typical Friedel-Crafts acylation reactions using A1C13. Entries 3 and 4 are similar, but include some functionality in the acylating reagents. Entry 5 involves formation of a mixed trifluoroacetic anhydride, followed by acylation in 85% H3PO4. The reaction was conducted on a kilogram scale and provides a starting material for the synthesis of tamoxifen. Entry 6 illustrates the use of bismuth triflate as... 

Azolides as acylating reagents are, of course, of special interest where the corresponding halides and anhydrides are not available due to their instability. Since neither... 

As mentioned before for other azolide reactions, acylations can be carried out with polymer-supported azolides as acylating reagents. For example, acetic acid hydrazide can be prepared with a polymer of l-acetyl-4-vinyl-imidazole/divinylbenzene (96 4) and hydrazine (no diacylation occurs when this method is used) [122]... 

In method B, iV-trifluoroacetylimidazole and carboxylic acids are the acylating reagents. This method is also thought to proceed via a carboxylic trifluoroacetic anhydride. This second system is a very convenient reagent for obtaining aromatic ketones because of the use of free carboxylic acids [97]... 

Scheme 7.109 Amide synthesis utilizing a reusable polymer-supported acylation reagent.

Similarly, a solid-supported imide has been reported to serve as an acylating reagent under microwave conditions by Nicewonger and coworkers [130], The starting imide was immobilized on aminomethyl polystyrene and in this case benzoyl chloride was chosen to prepare the acylating reagent (Scheme 7.111). Primary amines and piperazines were smoothly acylated at room temperature, but more hindered secondary amines required more time and higher temperatures, and anilines... 

Tab. 7.6. G raphite-supported acylation of anisole (51) by use of a variety of acylating reagents (RCOX) under the action of MW irradiation3 [27, 66].

The use of polymer-supported reagents in combinatorial chemistry has received much attention in recent years, and a polymer-supported acylating reagent (supported on a ROMPGEL) has been used for the synthesis of 1,2,4-oxadiazoles in solution, (see Equation 37), <2000CCHT131>. 

Acylbenzotriazoles 162 are efficient C-acylation reagents for the regioselective conversion of ketone enolates into P-diketones . Diethyl(l-benzotriazolmethyl)phosphinate (163) was found to be a convenient reagent for the stereoselective preparation of (E)-l-(l-alkenyl)benzotriazoles <00SC1413>. The novel three-carbon synthon 1-(1//-133-... 

The /3-lactone dimer of dimethylketene reacts with alcohols, phenols, mercaptans, and amines to form derivatives of 2,2,4-trimethylvaleric acid.3 In this respect it is a more powerful acylating reagent than the normal dimer, tetramethyl-l,3-cyclo-butanedione. The preparation of 2,2,4-trimethyl-3-oxovaler-anilide, for example, is accomplished easily with the lactone dimer, but is extremely difficult with the normal dimer.8... 

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