Tritylation, of sucrose

Tetramolar tritylation of sucrose in pyridine for 2 days at room temperature gave, after column chromatography on silica gel, 6,6 -di-... 

Tritylation of sucrose has been explored intensively [277-282] to show the low reactivity of the primary hydroxyl group at C-l of the p-D-fructofuranosyl moiety. Monotritylation of raffinose afforded the 6 -trityl and 6"-trityl ethers in 1.7 and 9.4% yields [283], whereas the 1, 6, 6"-tri-0-trityl derivative was the major product (20%) of the trimolar tritylation [284],... 

Tritylation offers an alternative (and less expensive) to silylation. Tritylation of sucrose can be achieved by heating it with an excess of chlorotriphenylmeth-ane (TrCl), leading to l -tri-O-tritylsucrose as the only product in 79% yield.67 The 6,6 -di-(9-tritylated derivative is obtained at room temperature.64,68 If this reaction is performed with 2.0 equiv. of TrCl, a mixture of both mono- (at C-6 and C-6 ) and ditritylated (C-6,6 ) derivatives is formed, but the overall yield decreases.69 If 1.2 equiv. is used, a mixture of both monotritylated derivatives (at C-6 and C-6 ) is formed in almost equal amounts, but in only 20% overall yield (Scheme 4).63... 

The trityl group has been used widely for the blocking of primary hydroxyl groups in carbohydrate chemistry (13). Tritylation of sucrose usually is... 

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). 

StericaHy hindered silyl ethers such as ferZ-hutyl dimethyl silyl, / fZ-butyldiphenylsilyl, and tricyclohexylsilyl have been proposed as alternatives to trityl ethers. Reaction of sucrose with 3.5 molar equivalents of ferZ-hutyl dimethyl silyl chloride produces the 6,1/6 -tri-O-silyl derivative in good yield (27). 

Acetates. Because of the significant interest in selective acetylation reactions of sucrose, the need for a convenient and unambiguous method of identification has been recognized (34,35). The position of an acetyl group in a partially acetylated sucrose derivative can be ascertained by comparison of its H-nmr acetyl methyl proton resonances after per-deuterioacetylation with those of the assigned octaacetate spectmm. The synthesis of partially acetylated sucroses has generally been achieved either by way of selectively protected derivatives such as trityl ethers and cychc acetals or by direct selective acetylation and deacetylation reactions. 

When 1 mole of sucrose was treated with 2 moles of chloro-triphenylmethane in pyridine for 96 h at room temperature, it gave, after counter-current distribution and column chromatography, mono-O-tritylsucroses, di-O-tritylsucroses, and 6,l, 6 -tri-0-trityl-... 

Trityl ethers and acetals of sucrose have generally been used as precursors for the synthesis of partially acylated derivatives of sucrose. Deacetalation of 3,4,3, 4 -tetra-0-acetyl-2,l 6,6 -di-0-(diphenylsilyl)sucrose (33) and 3,3, 4, 6 -tetra-0-acetyl-2,l 4,6-di-0-isopropylidenesucrose (35) with aqueous acetic acid for 25 min at 50° gave 3,4,3, 4 -tetra-0-acetylsucrose27 (34) and 3,3, 4, 6 -tetra-0-ace-tylsucrose32 (36), respectively. Synthesis of 2,3,4,3, 4 -penta-0-acetyl-... 

The ready condensation of sucrose with excess triphenylmethyl chloride in pyridine to a tri-trityl ether is, however, more easily explained by XV or II, which have three, instead of two (c/. I), primary alcohol groups to react selectively in the condensation. Fleury and Courtois oxidized sucrose for twenty-four hours at 14° with an excess of suitably buffered periodic acid and found that three moles of the oxidant were consumed and one mole of formic acid was eliminated. This highly selective oxidant is known to cleave unsubstituted 1,2 glycols quantitatively to two carbonyl groups and to eliminate the center carbon atom... 

A. S. M. Sofian, C. K. Lee, and A. Linden, Regioselective sulfonylation of 6,l, 6 -tri-0-trityl-sucrose through dibutyl-stannylation Synthesis of 4 -0-sulfonyl derivatives of sucrose, Carbohydr. Res., 337 (2002) 2377-2381. 

For ethyl D-fructofuranoside, both anomers are formed in small proportion during the hydrogenolysis of sucrose in ethanol. When the reaction was performed at 100° in an atmosphere of argon, considerable quantities were obtained. Ethyl S-D-fructofuranoside, [ ]d —36° (in water), is readily hydrolyzed to D-fructose by invertase (and also by 0.1 N sulfuric acid) at room temperature. The same behavior was observed for a substance isolated from wheat germ. Acetylation yielded a sirupy product, but treatment with trityl chloride gave crystalline methyl 1,6-di-O-trityl-D-fructoside (m.p. 180-183°). With p-toluenesulfonyl chloride, a crystalline product is obtained, with m.p. 125-127°. Ethyl a-D-fructofuranoside ([ ]d +65°, in water) is not attacked by invertase. Tritylation, followed by acetylation, gives ethyl 3,4-di-O-acetyl-l, 6-di-O-trityl-ai-D-fructofuran-oside m.p., 142-144° and [q ]d +44.5° (in chloroform). 

Trityl ethers of sucrose are often crystalline solids which are staible under basic and other nucleophilic conditions. The trityl protecting group cam be removed under mild acidic conditions as, for exaunple, hydrogen bromide in glacial acetic acid or boiling aqueous acetic acid. 

The well-known tri-tritylation of free sucrose provided derivative 7a, benzylation of which, followed by careful deprotection, afforded 2,3,3, 4,4 -penta-0-benzylsucrose (9). The main difficulty in the synthesis of 9 was encountered during hydrolysis of fully protected... 

Benzylation of the 5-amino-5-deoxy-pentoside 3 via its 2,3-O-dibutylstannylene derivative afforded a 1 1 mixture of the 2-0- and 3-0-benzyl ethers, whereas tritylation and silylation under the same conditions generated predominantly the 2-O-protected derivative. Similarly, benzylation of the D-erythronolactone 4 via its 0-dibutylstannylene derivative gave predominantly the 2-O-benzyl ether 5 while reductive opening (TiCU, HSiEts) of the corresponding 2,3-0-benzylidene compound afforded the 3-0-benzyl ether 6. Partial benzylation (0.9 eq NaH, DMF, BnBr) of sucrose has afforded 42% of 2-0-benzyl-sucrose, isolated as its 3,4,6,r,3, 4, 6 -heptaacetate. The molecular electrostatic potential profile of sucrose apparently predicts that the 2-OH group is the most electropositive of the eight hydroxy-groups. ... 

Another scheme for selectively modifying the C-6 hydroxyl group of sucrose involves the removal of the benzilidene group from 2,3,l, 3, 4, 6 -hexa-0-benzoyl-4,6-0-benzilidene sucrose by refluxing with iodine in methanol [25]. The resulting hexa-(9-benzoyl sucrose can be tritylated at C-6 and benzoylated at... 

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