Acetates acetyl migration

Trityl Ethers. Treatment of sucrose with four molar equivalents of chlorotriphenylmethyl chloride (trityl chloride) in pyridine gives, after acetylation and chromatography, 6,1, 6 -tri-O-tritylsucrose [35674-14-7] and 6,6 -di-O-tritylsucrose [35674-15-8] in 50 and 30% yield, respectively (16). Conventional acetylation of 6,1, 6 -tri-O-tritylsucrose, followed by detritylation and concomitant C-4 to C-6 acetyl migration using aqueous acetic acid, yields a pentaacetate, which on chlorination using thionyl chloride in pyridine and deacetylation produces 4,l, 6 -trichloro-4,l, 6 -trideoxygalactosucrose [56038-13-2] (sucralose), alow calorie sweetener (17). 

Orthoesters. The value of cycHc orthoesters as intermediates for selective acylation of carbohydrates has been demonstrated (73). Treatment of sucrose with trimethylorthoacetate and DMF in the presence of toluene-/)-sulfonic acid followed by acid hydrolysis gave the 6-0-acetylsucrose as the major and the 4-0-acetylsucrose [63648-80-6] as the minor component. The latter compound underwent acetyl migration from C-4 to C-6 when treated with an organic base, such as / fZ-butylamine, in DMF to give sucrose 6-acetate in >90% yield (74). When the kinetic reagent 2,2-dimethoxyethene was used,... 

Acetyl migration between neighbouring hydroxy-groups affords a mixture ca. 1 3) of the 16- (43) and 17-acetates (45) of a 16/(,17/ -diol, when either of the acetoxy-ketones (42) or (44) is reduced with borohydride. " ... 

Rhodosporidium toruloides, 54-88% yield. A number of peracetylated glycosides were hydrolyzed selectively at the 6-hydroxyl. These derivatives when treated with acetic acid undergo acetyl migration to give the C4-deprotected monosaccharide. ... 

Deprotection and sulfation was achieved by reduction of the azide to the corresponding acetamide with thioacetic acid [75] to afford III.47 (Scheme 29). Subsequent de-levulinoylation followed by acetylation gave III.48 in 64% yield over two steps. Reductive opening of the bisbenzylidene acetals with sodium cyanobo-rohydride and acid [76] afforded III.49 in 51% yield and by-product III.50, formed by acetyl migration from C3 to C4 (31%). Sulfation of III.49 was carried out with the sulfur trioxide-trimethylamine complex to give III.51 in 92% yield. Deacetylation followed by hydrogenolysis provided the target tetrasaccharide III.52. 

Monoacetates of the corticosteroid dihydroxyacetone side-chain are not ordinarily accessible because of their propensity for acetyl migration to C-21. Hydrolysis of the 17,21-orthoacetate (119) in a phthalate buffer at pH 3, however, gave the 17-acetate (120) in high yield,presumably through kinetically-controlled protonation at the more-exposed C-21 oxygen atom. 

Acetates are the most commonly used of the esters for hydroxyl protection, particularly for peracylation (Figure 2.32) [47] although selective partial acetylation can be achieved, the tendency of acetates to migrate can lead to a loss in observed selectivity. In some cases, as with silyl ethers, migration can be sufficiently reliable to be synthetically useful for example, acetate migration can be used efficiently to lead to simultaneous release of the 4-OH and protection of the 6-OH in glucose derivatives (Figure 2.33) [48]. 

Peracetylated D-glucal, D-galactal, and D-rhamnal were selectively deprotected at 04 by treatment with hydrazine acetate in DMF (see Vol.20, Chapter 13, ref.3). The possibility of initial deacetylation at the primary position followed by 4- 6 acetyl migration was excluded on the basis of experiments with deuteroacetylated starting compounds." The 4->6 acetyl migration to give the 3,6-diacetate (14) from its 3,4-isomer (13) has been studied in some detail and optimized in order to prepare (l->4)- and (l- 6)-linked disaccharides from a common carbohydrate aglycon (see Chapter 3). ... 

Acylation. Reaction conditions employed to acylate an aminophenol (using acetic anhydride in alkaU or pyridine, acetyl chloride and pyridine in toluene, or ketene in ethanol) usually lead to involvement of the amino function. If an excess of reagent is used, however, especially with 2-aminophenol, 0,A/-diacylated products are formed. Aminophenol carboxylates (0-acylated aminophenols) normally are prepared by the reduction of the corresponding nitrophenyl carboxylates, which is of particular importance with the 4-aminophenol derivatives. A migration of the acyl group from the O to the N position is known to occur for some 2- and 4-aminophenol acylated products. Whereas ethyl 4-aminophenyl carbonate is relatively stable in dilute acid, the 2-derivative has been shown to rearrange slowly to give ethyl 2-hydroxyphenyl carbamate [35580-89-3] (26). 

Analogous acyl migrations occur with dienol acetates of type (238) and (239), yielding products from the two possible recombinations—(240)/(241) and (243)/(244), respectively—besides the products of reductive acetyl elimination (see Experiment b below). 

Ion 21 can either lose a proton or combine with chloride ion. If it loses a proton, the product is an unsaturated ketone the mechanism is similar to the tetrahedral mechanism of Chapter 10, but with the charges reversed. If it combines with chloride, the product is a 3-halo ketone, which can be isolated, so that the result is addition to the double bond (see 15-45). On the other hand, the p-halo ketone may, under the conditions of the reaction, lose HCl to give the unsaturated ketone, this time by an addition-elimination mechanism. In the case of unsymmetrical alkenes, the attacking ion prefers the position at which there are more hydrogens, following Markovnikov s rule (p. 984). Anhydrides and carboxylic acids (the latter with a proton acid such as anhydrous HF, H2SO4, or polyphosphoric acid as a catalyst) are sometimes used instead of acyl halides. With some substrates and catalysts double-bond migrations are occasionally encountered so that, for example, when 1 -methylcyclohexene was acylated with acetic anhydride and zinc chloride, the major product was 6-acetyl-1-methylcyclohexene. ... 

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