Hydroxy compounds, acylation reactions

The second group of hydroxy compound derivatization reactions includes acylation of OH groups with the formation of esters. The most important are listed below (for the table of physicochemical and gas chromatographic constants of acylation reagents refer to the entry Derivatization of Amines, Amino Acids, Amides, and Imides for GC Analysis). 

The second group of hydroxy compound derivatization reactions includes acylation of OH groups with the formation of esters. The most important are listed in the Table 6. 

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). 

The results presented in Tables 3 and 4 deserve some comments. First, a variety of enzymes, including whole-cell preparations, proved suitable for the resolution of different hydroxyalkanephosphorus compounds, giving both unreacted substrates and the products of the enzymatic transformation in good yields and, in some cases, even with full stereoselectivity. Application of both methodologies, acylation of hydroxy substrates rac-41 and rac-43 or the reverse (hydrolysis of the acylated substrates rac-42 and rac-44), enables one to obtain each desired enantiomer of the product. This turned out to be particularly important in those cases when a chemical transformation OH OAc or reverse was difficult to perform. As an example, our work is shown in Scheme 3. In this case, chemical hydrolysis of the acetyl derivative 46 proved difficult due to some side reactions and therefore an enzymatic hydrolysis, using the same enzyme as that in the acylation reaction, was applied. Not only did this provide access to the desired hydroxy derivative 45 but it also allowed to improve its enantiomeric excess. In this way. 

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)...

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]. 

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... 

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... 

The reaction of acyl chlorides with hydroxy compounds and amines has already been met in previous experiments. Generally, hydroxy compounds, ROH, primary amines, RNHj, and secondary amines, R2NH, react Avith acyl chlorides, the reactive hydrogen being replaced by the acyl group ... 

E) Alcoholysis of Acyl Chlorides. Add 5 drops of acetyl chloride to 1 ml of ethanol. What is the product resulting from this reaction Can this test be used for detection of the hydroxyl group If so, try it with a less reactive hydroxy compound. 

N-(l-Alkoxyalkyl)-aniides or -carbamates (2 X = OR), most frequently used as stable precursors for A -acyliminium ions, are usually prepared by one of the following routes (equations 7-13). For five- or six-membered cyclic cases a simple acid-catalyzed solvolysis of the hydroxy compound provides the alk-oxy derivative (equation 7). A silicon-assisted approach involves the TMSOTf-catalyzed reaction of bis(trimethylsilyl)formamide with aldehydes (equation 8). /V-(l-Trimethylsilyloxyalkyl)formamides are thus formed in good yields, which on TMSOTf-catalyzed solvolysis lead to the /V-( 1-alkoxyalkyl)form-amides. A third method is based on the NaBH4 reduction of imidates (equation 9), and has proved useful for a total synthesis of the insect poison pederine. Addition of reactive acid derivatives to imines constitutes another method (equations 10 and 11). Acylation with acid chlorides followed by treatment with ethanol in the presence of base leads to N-(l-alkoxyalkyl)amides. A one-step protocol using diethyl dicarbonate provides the corresponding carbamates. 2... 

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