Hydroxy compounds, acylation

Cocatalysts of two types occur (/) proton-donor substances, such as hydroxy compounds and proton acids, and (2) cation-forming substances (other than proton), including alkyl and acyl haUdes which form carbocations and other donor substances leading to oxonium, sulfonium, halonium, etc, complexes. 

Regioselective Acylation of Hydroxy Compounds. AUphatic diols can be selectively acylated at the primary position by a number of Upases in nonaqueous solvents. For example, PPL suspended in solutions of various diols in ethyl carboxylates catalyzes transesterification in a highly regioselective manner, producing primary monoesters in up to 97% yield (93). Similarly, chloramphenicol [56-75-7] (72) (R = NO2) can be acylated by a number of Upases to produce optically pure, water-insoluble 3-0-palmitate in a highly selective manner (94). 

The A-(l-acyloxyalkyl)amides or carbamates arc easily prepared from the corresponding hydroxy compounds by conventional acylation methods, such as heating with the required carboxylic acid in the presence of a strong acid or treatment with acyl halides or acid anhydrides1. 

Studies of Trifluoroacetic Acid. Part XV. Further Investigations on the Reactions of Acyl Trifluo-roacetates with Hydroxy-compounds, E. J. Bourne, M. Stacey, J. C. Tatlow, and R. Worrall,... 

Hydroxy-L-prolin is converted into a 2-methoxypyrrolidine. This can be used as a valuable chiral building block to prepare optically active 2-substituted pyrrolidines (2-allyl, 2-cyano, 2-phosphono) with different nucleophiles and employing TiQ as Lewis acid (Eq. 21) [286]. Using these latent A -acylimmonium cations (Eq. 22) [287] (Table 9, No. 31), 2-(pyrimidin-l-yl)-2-amino acids [288], and 5-fluorouracil derivatives [289] have been prepared. For the synthesis of p-lactams a 4-acetoxyazetidinone, prepared by non-Kolbe electrolysis of the corresponding 4-carboxy derivative (Eq. 23) [290], proved to be a valuable intermediate. 0-Benzoylated a-hydroxyacetic acids are decarboxylated in methanol to mixed acylals [291]. By reaction of the intermediate cation, with the carboxylic acid used as precursor, esters are obtained in acetonitrile (Eq. 24) [292] and surprisingly also in methanol as solvent (Table 9, No. 32). Hydroxy compounds are formed by decarboxylation in water or in dimethyl sulfoxide (Table 9, Nos. 34, 35). 

Fig. 9. Biotransformation of dihydroquinidine (and acylated derivatives) to the corresponding (3S)-3-hydroxy compounds (as % observed at the reaction plateau), using various collection strains of Mucor plumbeus (ATCC American Type Culture Collection CBS Centraalbureau voor Schimmelcultures DSM Deutsche Sammlung von Mikroorganismen MMP Mycotheque of the Paris Museum of National History)...

Regioselective Acylation of Hydroxy Compounds. Aliphatic diols can be selectively acylated at the primary and secondary positions by a number of lipases in nonaqueous solvents... 

Cobalt complexes derived from Schiff bases 388 catalyzed the hydroxyacylation of electron-deficient alkenes (Fig. 90) [431, 432]. Thus, methyl acrylate 387 reacted with aliphatic aldehydes 386 in the presence of 5 mol% of the in situ generated catalyst, molecular oxygen, and acetic anhydride to 2-acyloxy-4-oxoesters 389 in 56-77% yield. When acetic anhydride was omitted, the yields of products were lower and mixtures of the free hydroxy compounds and acylated compounds resulting from Tishchenko reactions were obtained. Electron-rich alkenes did not undergo the transformation, since the addition of the acyl radical is much slower. The acylcobalt species inserts oxygen instead and acts as an epoxidation catalyst. 

In mixed trifluoroacetic anhydrides, the strong electron-withdrawing tri-fluoroacetyl group polarizes the bonds to the anhydride oxygen in such a way that it tends to split to acylium cation and trifluoroacetate anion [/0/. Generally, the products of the reaction of hydroxy compounds with acyl trifluoroacetates are esters of carboxylic acids and trifluoroacetic acid, because the acyl carbonyl is better fit for a nucleophilic attack than the carbonyl next to the trifluoromethyl group [707]. 

Action of Acyl Halides on Hydroxy Compounds RCOa + R OH - RCOjR + HCl... 

Anhydrides have been used in the acylation of hydroxy compounds containing halo, aldehyde/ keto/ and nitrd groups. 

Both the AT-hydroxy compounds and the A/ -oxides which are in tautomeric equilibrium with hydroxy compounds form O-acyl and O-aroyl compounds, and such esters can act as... 

The 3-amino substituent of various [l,2,4]triazoIo[4,3-a]pyrazines can be acylated (69JCS(C)1593) but it is inert towards normal diazotization procedures (68JHC485). The 3-hydroxy compound could not be chlorinated with phosphorus oxychloride and in the IR spectrum it appeared to exist in both the keto and enol forms (68JHC485). 

The reaction in Scheme 3 for HOR = HODhbt is accompanied by a side reaction giving rise to the formation of oxobenzotriazinyl 2-azidobenzoate 50 (Scheme 10). ] The 2-azido-benzoate originates from reaction of HODhbt (48) with addition product 49 formed by reaction of the carbodiimide with 48. It is detectable by HPLC and by the azide absorbance at 2120 cm" in the IR spectrum. It is an acylating agent and thus causes chain termination if left as a contaminant of the ester. The side reaction is completely eliminated by allowing a 5-minute activation time before addition of the hydroxy compound.0 5 l... 

Pentafluorophenyl 61 and 4-oxo-3,4-dihydrobenzotriazin-3-yl 65 esters (see Table 16) can be obtained from acid 59 and hydroxy compounds using thionyl chloride the intermediate is the Fmoc amino acid chloride 64 (Scheme 17). In the case of the pentafluorophenyl esters 61, the acid chloride 64 is generated in the absence of the nucleophile and acylation is promoted in the presence of pyridine. While in the case of the 4-oxo-3,4-dihydrobenzotriazin-3-yl esters 65, condensation is achieved by heating the reactants in refluxing dichloromethane. The method is not applicable to derivatives with acid-sensitive side-chain protectors. 

Water-dispersible lecithins are made by chemical modification, or by mixing ordinary lecithin with nonionic surfactants. Many of the products recommended in the literature and technical brochures for water-based compositions include such chemically modified, water-dispersible, lecithin compounds (e.g., hydroxy-lated, acylated, fractionated, and refined grades) (428, 431 33). Usually 0.5% to 1% modified lecithin is recommended in polyvinyl acetate-based paints, acrylic emulsions, and in butadiene—styrene emulsion paints. 

The Reaction of Acyl Trifluoroacetates with Hydroxy Compounds. 81... 

The replacement of the hydrogen atom in a hydroxyl group by the tri-fluoroacetyl group is effected by the usual acylation procedure of warming the hydroxy compound with trifluoroacetic anhydride in the presence of dry sodium trifluoroacetate under anhydrous conditions. The recovery of the ester requires, however, a modified procedure, since the usual method of destroying the excess acid anhydride by means of aqueous sodium bicarbonate simultaneously brings about hydrolysis of the alkali-labile trifluoroacetate group. In order to remove excess trifluoroacetic anhydride and the trifluoroacetic acid present under anhydrous conditions, the reaction mixture is distilled several times with dry carbon tetrachloride and... 

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