Acetyl chloride with phenol

Also obtained by reaction of acetyl chloride with phenol in the presence of aluminium chloride at 120° [3953],... 

Materials. N,N-Dimethylformamide (DMF) and N-methyl-2-pyrrolidone (NMP) were stirred over powdered calcium hydride overnight, distilled under reduced pressure, and then stored over 4-A molecular sieves. 4-Aminobenzhydrazide (5) was prepared from methyl 4-aminobenzoate and hydrazine monohydrate according to the reported procedure (6). 4,4 -Thiobisbenzenthiol (6) and isophthalic acid (7) were purified by reciystdlization. Phenyl acrylate and 4-nitrophenyl acetate were prepared by the reactions of acryloyl chloride or acetyl chloride with phenol or 4-nitrophenol in the presence of triethylamine and tetahydrofuran, respectively. TrieAylamine (TEA) and tetahydrofuran (THF) were purified by the usual method. Other reagents and solvents were obtained commercially and used as received. 

Preparation by reaction of acetyl chloride with p-(trifluoro-methyl)phenol in hydrofluoric acid for 6 h to 100° under 3 atm (88%) [2476]. 

Sulfonated styrene—divinylbensene cross-linked polymers have been appHed in many of the previously mentioned reactions and also in the acylation of thiophene with acetic anhydride and acetyl chloride (209). Resins of this type (Dowex 50, Amherljte IR-112, and Permutit Q) are particularly effective catalysts in the alkylation of phenols with olefins (such as propylene, isobutylene, diisobutylene), alkyl haUdes, and alcohols (210) (see Ion exchange). Superacids. 

These can be prepared as for the benzoates using either acetic anhydride with 3N NaOH or acetyl chloride in pyridine. They are hydrolysed as described for the benzoates. This hydrolysis can also be carried out with aqueous 10% NaOH solution, completion of hydrolysis being indicated by the complete dissolution of the acetate in the aqueous alkaline solution. On steam distillation, acetic acid also distils off but in these cases the phenols (see above) are invariably solids which can be filtered off and recrystallised. 

Isotope labeling by derivative formation with deuterated reagents is useful for the preparation of analogs such as dg-acetonides, da-acetates, da-methyl ethers, dg-methyl esters, etc. The required reagents are either commercially available or can be easily prepared. (The preparation of da-methyl iodide is described in section IX-F. Various procedures are reported in the literature for the preparation of dg-acetone, da-diazometh-ane57.i63.i73 and da-acetyl chloride. ) These reactions can be carried out under the usual conditions and they need no further discussion. A convenient procedure has been reported for the da-methylation of sterically hindered or hydrogen bonded phenolic hydroxyl functions by using da-methyl iodide and sodium hydroxide in dimethyl sulfoxide solution. This procedure should be equally applicable to the preparation of estradiol da-methyl ether derivatives. 

The sulfide derivative of furocoumarin based natural products can be synthesized by treatment of a thiadiazole 107 with KO-f-Bu and an organohalide in an one-pot operation. This process presumably involves the generation of a phenolate 108 and is followed by an intramolecular proton shift and a rearrangement to give an alkynethiolate 109, which undergoes a sequence of intramolecular proton shift, cyclization and alkylation to lead to the furocoumarin product. The thiadiazole, in turn, can be prepared by reaction of the corresponding acetyl precursor with carbethoxyhydrazine, followed by treatment with thionyl chloride . 

Even the mildest pulping process, hydrotropic extraction, i.e. repeated extraction with concentrated aqueous solutions of organo-philic electrolytes such as sodium xylenesulfonate or cymenesulfonate, has failed because of an outlet for the extracted lignin, wliich is precipitated by mere dilution of the solution. Other methods based on hydrolysis of the wood with acids, e.g. HCl, HNO3, AICI3, acetic acid, acetyl chloride, SOg, or phenol, are merely of laboratory interest. 

With acetyl chloride, the carboxyl groups were acetjdated as well as the phenols (45). The resulting acetyl contents were equivalent to the NaOH neutralization. 

Acetic acid has been found to react with toluene to form p-methylace-tophenone (Simons et al., 49), to react with benzene to form acetophenone, and to react with phenol to form p-hydroxy acetophenone. Acetyl chloride also formed acetophenone with benzene and acetic anhydride reacted with toluene to form both p-methylacetophenone and 2,4-diace-tyltoluene. Valeric acid reacted with toluene to form p-tolyl-n-butyl ketone. Both benzoic acid and benzoyl chloride reacted with toluene to form p-tolylphenyl ketone. Acenaphthene with either benzoic acid or benzoyl chloride gave 3-benzoylacenaphthene (Fieser and Hershberg,... 

These hydroxyl groups in polymers are also usually determined by acetylation [9,21] or bromination [23]. However, it should be noted that acetylation with acid anhydrides and acyl chlorides that only total hydroxyl groups in these resins can be determined [7], Aromatic sulfonyl chlorides, however, react selectively with phenolic hydroxyls [26]. 

The reactions of 0-naphthol and 4-methoxyphenol with acetyl, propionyl, butyryl, 0-chloropropionyl and chloracetyl chlorides in acetonitrile produce some striking kinetic results109. The behaviour of acetyl, propionyl and n-butyryl chlorides fit reasonably well into the pattern for acetyl chloride in nitromethane and acetyl bromide in acetonitrile. However, with chloracetyl chloride the mechanism is essentially a synchronous displacement of covalently bound chlorine by the phenol and this process is powerfully catalysed by added salt with bond breaking being kinetically dominant. When no added salt is present the rate of hydrolysis of chloracetyl chloride is ca. 8000 times slower than that of acetyl chloride. Although, normally, in second-order acylation reactions, substituents with the greatest electron demand have been found to have the fastest rates, the reverse is true in this system. Satchell proposes that a route such as... 

Phenoxy-substituted 2H, 8 -naphtha [l,2,3-de]-benz[/j]-2,8-quinolinedione (IIIC, R2 = hydrogen, R3 = CH3) was synthesized by cyclization of TV-chloro-acetyl-6-aminonaphthacenequinone in pyridine to the corresponding naphthacenepyrido-nyl-3-pyridinium chloride, with the subsequent reductive elimination of the pyridi-nium residue.39 The 3-acetyl derivative was obtained by the interaction of 6-amino-ll-chloro-5,12,naphthacenequinone with acetic anhydride in phenol in the presence of anhydrous sodium carbonate.39... 

Incidental reactions that have been reported include the preparation of derivatives of 5-(hydroxymethyl)-2-furaldehyde by reaction of D-fructose in acetic or propionic acid in the presence of the respective anhydride.158 The condensation of D-glucose with phenol has been effected in acetic acid in the presence of dry hydrogen chloride, prior to resinification,157 and the reaction of sucrose with thionyl chloride in acetic acid-acetic anhydride produced partially acetylated chlorodeoxysucroses.158 Sucrose has been condensed with maleic anhydride in acetic anhydride mixed with acetic acid or formic acid, to give solid products having an undetermined structure.159... 

Alternative methods for the formation of the catechol (5) were examined, and these serve to show other methods for introduction of the hydroxy group. Nitration of triene (6) followed by reduction to the amine and diazotization in the presence of methanol gave the phenol (8), but only in poor yield. The best method developed appears to be acetylation of the triene (6) with titanium tetrachloride/acetyl chloride to give the ketone (9), followed by Baeyer-Villiger oxidation to die acetate (10), which on hydrolysis afforded the catechol (8) in 70% overall yield. 

Acetylation of phenols and anilines. These substrates can be acetylated rapidly and in generally high yield by reaction with acetyl chloride using powdered NaOH and tetrabutylammonium hydrogen sulfate in an organic solvent (CH2CI2, dioxane, THE). Even 2,6-di-f-butyI-p-cresol can be acetylated in this way in 72% yield. Selective acylation of the phenolic hydroxyl group of estradiol is possible. ... 

On treatment of 11 with palladium, an interesting disproportionation reaction takes place which yields the colorless indole derivative 14 (27,28). Reaction of betanidin with acetyl chloride in trifluoroacetic acid afforded di-C>-acetyl-betanidin (13), which could be hydrolyzed back to 1 with concentrated hydrochloric acid (5). This demonstrated the presence of two phenolic hydroxyl groups in betanidin, and from consideration of the H-NMR data formula 1 was assigned to betanidin. 

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