Trityl ether

One monotrityl-D-fructose has been prepared. By treating D-fructose with an equimolecular amount of trityl chloride in pyridine for one day at room temperature, Helferich and Bredereck78 obtained a 12% yield of crystalline 1-trityl-D-fructose, m. p. 170°, [ ]d —26.2° — +4.2° in pyridine. Proof of structure of this compound depends on the preparation of fceto-D-fructose 3,4,5,6-tetraacetate, already discussed (page 63). 

Reaction of D-fructose with two molecular proportions of trityl chloride in pyridine for two days at room temperature gave a ditrityl-D-fructose (30% yield), which crystallized (m. p. 96-97°) with two molecules of pyridine. Removal of the pyridine left amorphous ditrityl-D-fructose, [a]D +17.5° in chloroform. This gave a crystalline oxime identical with that obtained by tritylating D-fructose oxime. Helferich148 designates this ditrityl derivative as 1,6-ditrityl-D-fructose without further proof. 

Trityl (triphenyl methyl) ethers are formed by reaction of the carbohydrate, usually dissolved in pyridine, with trityl chloride (triphenylchloromethane). This reagent shows a high degree of regioselectivity for reaction with primary hydroxyl groups in the presence of secondary hydroxyl groups, due to the high de- 

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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). 

These hindered silyl ethers are generally more stable to acid hydrolysis than their trityl ether equivalents and can be removed using... 

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. 

Ethers are among the most used protective groups in organic synthesis. They vary from the simplest, most robust, methyl ether to the more elaborate, substituted, trityl ethers developed for use in nucleotide synthesis. They are formed and removed under a wide variety of conditions. Some of the ethers that have been used to protect alcohols are included in Reactivity Chart 1. ... 

Triphenylmethyl ethers (trityl ethers) have been used to protect primary alcohols selectively [see (14)] , and unhindered secondary alcohols. 

As previously discussed, ethyl chlorocarbonate reacts rapidly and selectively with an equatorial 3-hydroxyl group to give the corresponding cathylate. Trityl ethers, usually employed as a selective protecting group for primary hydroxyls, can be prepared from A -3j3-ols by heating with triphenylmethyl chloride in pyridine, and from 5a-3 -alcohols by more prolonged heat-... 

Dimethoxy-3 - [A-(imidazolylethyl)carbamoyl]trityl Ether (lETr-OR) ... 

Trimethylsilylated alcohols, phenols, or carboxylic acids 13 react with trimefhyl-silylated triphenylcarbinol 792 in the presence of TMSOTf 20 to give the trityl ethers 793, in 73-98% yield, and HMDSO 7 [14] (Scheme 6.6). 

Clean removal of trityl ether groups from O-isopropylidenated furanoses by using NaHS04-Si02 was previously described by Das et al.116 and afforded the corresponding alcohols at room temperature. The chemoselective deprotection was accomplished in yields above 91% within 2-2.5 h, leaving other protective-groups intact (Scheme 27). 

Furthermore, several functionalities remained unaffected, namely the acid-labile TBDMS or PMB groups.118 Deprotection yields were in the range of 85-95% when methanol was used at room temperature as the solvent, whereas acetonitrile or dichloromethane led to very sluggish or nonexistent reactions, respectively. Cleavage of primary trityl ethers was also accomplished using the same conditions in a very rapid and effective fashion. The trityl pyranosides and furanosides assayed were selectively deprotected in 2-3 h and yields higher than 85% were achieved. This reaction was also more efficient when conducted in methanol, which acts as a nucleophile to trap the generated trityl cation. 

B. Das, G. Mahender, V. S. Kumar, and N. Chowdhury, Chemoselective deprotection of trityl ethers using silica-supported sodium hydrogen sulfate,... 

A. Agarwal and Y. D. Vankar, Selective deprotection of terminal isopropylidene acetals and trityl ethers using HCIO4 supported on silica gel, Carbohydr. Res., 340 (2005) 1661-1667. 

Because of the high stability of the triphenylmethyl carbocation, the reductive ether cleavage of trityl ethers with EtySiH/trimethylsilyl triflate (TMSOTf) is highly successful. This reaction even occurs in the presence of highly reactive sugar ketals, leaving the ketals intact (Eq. 126).269... 

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-... 

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