Acetyl under acidic conditions

A-Acylations of 57/-dibenz[b,/]azepine (5) can be carried out under standard conditions,69 124 142,196 197 as exemplified below. There is some evidence to suggest that acetylation under acidic conditions is accompanied by ring contraction to yield acridones.32... 

The 4-amino group of 31 was selectively acetylated under acidic conditions using acetic anhydride (1 equiv.) and methanesulfonic acid (1 equiv.) in acetic acid and f-butylmethyl ether to give 32. Deallylation of 32 using 10% Pd/C in the presence of ethanolamine in refluxing ethanol proceeded as before to afford 1, which was converted to the phosphate salt in 70% yield with high purity (99.7%). The overall yield of 1 from epoxide 23 was 35-38%. 

In 1942, Hann, Haskins and Hudson48 reported that the di-(o-nitro-benzylidene)-dulcitol described by Tanasescu and Macovski was not oxidized by lead tetraacetate and therefore could not possess the structure (1,2 5,6) arbitrarily assigned to it by the earlier workers. In view of the fact that the diacetal gave the known l,3,4,6-tetraacetyl-2,5-diben-zoyl-dulcitol when it was benzoylated in pyridine and then acetylated under acidic conditions, they regarded it as l,3 4,6-di-(o-nitrobenzyli-dene)-dulcitol, but of course this conclusion is not unequivocal. 

Oxidation of the 2-hydroxyglycal ester (3) with w-chloroperbenzoic acid gave the anomeric hexos-2-uIose acetates (4) and (5) which, on acetylation under acidic conditions, gave the a-hexa-acetate (6). Alternatively, acetyl chloride in pyridine led to the jS-enediol penta-acetate (7) further elimination gave the 7-pyrone (8). The chemistry of these and several other reactions has been described in a lengthy paper and is outlined in Scheme 5. The chlorination of 2-hydroxyxylal esters is described in Chapter 7. 

When the phenol contains a carboxylic acid group, e.g., m- or p-hydroxy-benzoic acid, the acetylated derivative will of course remain in solution as the sodium salt, but is precipitated when the solution is subsequently acidified. Salicylic acid, however, cannot be acetylated under these conditions. 

Salicylic acid, however, cannot be acetylated under these conditions. 

For the formation of substituted THF rings (Route a, Scheme 8.1), Kishi developed a procedure based on the hydroxy-directed epoxidation of a y-alkenol [10]. Epoxidation of bishomoallylic alcohol 3 by TBHP/VO(acac)2 by this approach, followed by treatment of the intermediate epoxide 4 with acetic acid, gave the TH F derivative 5 of isolasalocid A (a 5-exo cydization Scheme 8.2) [11]. Further epoxidation of 5 (a y-alkenol) under the same conditions, followed by acetylation, afforded epoxide 6. For the synthesis of the natural product, the configuration of epoxide 6 had to be inverted before the second cydization reaction. Epoxide 6 was consequently hydrolyzed under acid conditions to the corresponding diol and was then selectively... 

A direct formation of 5-22 [e. g., of 2-amino-4-cyclopentene-l,3-diol (5-22, Nu = OH)], is observed if the photochemical reaction of 5-19 is performed under acidic conditions using HC104. After acetylation, the formed diacetate can be isolated in about 25 % yield. 

Dakin, H. D. West, R. J. Biol. Chem. 1928, 78, 91, 745, and 757. In 1928, Henry Dakin and Rudolf West, a clinician, reported on the reaction of a-amino acids with acetic anhydride to give a-acetamido ketones via azalactone intermediates. Interestingly, one year before this paper by Dakin and West, Levene and Steiger had observed both tyrosine and a-phenylananine gave abnormal products when acetylated under these conditions.Unfortunately, they were slow to identify the products and lost an opportunity to be immortalized by a name reaction. 

Finally, Lecomte and coworkers reported the synthesis of mikto-arm star-shaped aliphatic polyesters by implementing a strategy based on click chemistry (Fig. 36) [162]. Firstly, the polymerization of sCL was initiated by a diol bearing an alkyne function. The chain-ends were protected from any further undesired reaction by the esterification reaction with acetyl chloride. The alkyne was then reacted with 3-azidopropan-l-ol. The hydroxyl function located at the middle of the chain was then used to initiate the ROP of sCL and y-bromo-s-caprolactone. Finally, pendant bromides were reacted successfully with sodium azide and then with N, N-dimethylprop-2-yn-l-amine to obtain pendant amines. Under acidic conditions, pendant amines were protonated and the polymer turned out to exhibit amphiphilic properties. 

With the nitrogen atom well protected as the cyclic carbamate 105, all attempts to open the 1,6-anhydro ring under acidic conditions failed owing to the lability of the two allylic benzyl ethers present in the molecule. However, it was possible to debenzylate 105 with lithium in ammonia to form the new cyclic carbamate 108 and acetylation then gave 109. 

Condensation of the readily available N-pivaloyl ketone 259 (Scheme 77) with N-acetyl indolin-3-one (558) under acid conditions provides good yields of 1 l-azapyrido[3,4-6]carbazole 559, which represents an aza analogue of ellipticine (Scheme 168) (89JHC105). 

Unsaturated ketonucleosides have been shown to be remarkably stable under acidic conditions. 7-(3-0-Acetyl-4,6-dideoxy-/ -L-g/t/cm>-hex-3-enopyranosyl-2-ulose)theophylline (61a) proved to be stable in 0.1 M hydrochloric acid, as no glycosylic cleavage had occurred51 after 20 h. Similarly, no decomposition was observed when 7-(3,6-di-0-ace-tyl-2-deoxy-/ -D-gh/cero-hex-2-enopyranosyl-4-ulose)theophylline (66) was treated with 0.1 M sulfuric acid during 48 h at room temperature, and attempted, ionic hydrogenation with triethylsilane - trifluoroacetic acid failed.31... 

The instability of the 3-hydroxymethylindoles over a wide pH range results in the lack of success in acetylation of the hydroxy compound and also in the failure to hydrolyze the acetoxymethylindole without conversion into the bis(3-indolyl)methane (79HC(25-3)l). In contrast with the 3-isomer, 2-hydroxymethylindoles are stable to bases, but are polymerized by acids (79HC(25-3)l). Similarly, it is possible to convert 3-hydroxymethylpyrroles into their acetates and methyl ethers under basic conditions, and reaction with isocyanates yields the expected urethanes (79JMC977). Under acidic conditions, however, they produce the bis(3-pyrrolyl)methanes (B-77MI30504). 

Benzofuran-3(2/f)-ones (396) exist in the keto form but undergo ready enolization. Acetylation with acetic anhydride and sodium acetate affords 3-acetoxybenzo[6]furans, but reaction under acidic conditions usually supplies these products admixed with 3-acetoxy-2-acetylbenzo[6]furans. Alkylation usually furnishes a mixture of O- and C-alkylated products. 3-Acetoxy-6-methoxy-4-methylbenzo[6]furan, on Vilsmeier reaction, supplies the 3-chlorobenzo[6]furan-2-carbaldehyde, the product expected from an enolizable ketone (72AJC545). Benzofuran-3(2//)-ones react normally with carbonyl reagents. Grignard reagents react in the expected way and dehydration of the intermediate affords a 3-substituted benzo[6]furan. The methylene group is reactive so that self condensation, condensation with aldehydes and ketones and reaction with Michael acceptors all occur readily. 

At the outset, an a-dimethylation leads to compound 17. Reduction of the ketone to secondary alcohol 18 and acetylation of the latter provides ester 19 The ester group functions under acidic conditions as a leaving group, and it is replaced by a hydride anion with formation of compound 20. The last step is a Birch reduction These five steps were accomplished with an overall yield of 85%. 

The acetyl bromide procedure was developed by Johnson et al. (1961) to determine lignin content in small samples from woody species. This method uses acetyl bromide (4.10) to acetylate unbound hydroxyl groups in the lignin (4.11), while the hydroxyl group on the a-carbon is substituted with a bromine group. The substituted lignin derivative (4.12) is soluble under acidic conditions, and its concentration can be measured with a spectrophotometer at 280 nm. 

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