Trimethylsilyl derivative

Conversion of sugars into their O-trimethylsilyl (Me3Si) derivatives is most commonly achieved by reaction in pyridine with hexamethyl-disilazane (1) and chlorotrimethylsilane (2) according to equation (I). 

In a typical procedure, 10 mg of a sugar is dissolved in 1 ml of pyridine, treated successively with 0.2 ml of hexamethyldisilazane and 0.1 ml of chlorotrimethylsilane, and the mixture shaken for a few seconds. Reaction is normally complete within 5 minutes. This treatment corresponds to the original procedure used by Sweeley and colleagues,5 and is the method used in the great majority of cases. Apart from the deliberate use of other trimethylsilylating reagents, most of the variations on this fundamental reaction have been designed to meet certain special conditions. 

With simple compounds, the trimethylsilylation reaction is rapid, but, if the reaction proceeds slowly, short reaction-times lead to incomplete substitution this is generally manifest on the gas chromatogram because of the presence of an unexpectedly large number of peaks.117 Maltose has been reported to require reaction for at least 30 minutes,118 and the time needed for complete trimethylsilylation of amino sugars has been examined by Oates and Schrager.36 

Ketoses appear to react slowly, and several authors have commented on the time required for complete trimethylsilylation of D-fructose. Thus five peaks were observed after trimethylsilylation for one hour, compared to three peaks when the reaction was allowed to continue for 24 hours.119-123 Sorbose reacts in a similar, slow man- 

Trimethylsilylation normally proceeds without any change in the carbohydrate, but glucosinolates have been found126 to undergo desulfation during the reaction it was also observed that, even though trimethylsilylation was conducted overnight at 105°, only 80% reaction was obtained. 

Another method for the separation of methylated compounds consists in converting the reducing, methylated sugar into the trimethylsilyl derivative or, less commonly, into the acetate. Multiple peaks can be formed, but, although these may complicate the chromatogram, their relative intensities and positions may aid in the identification. Alternatively, methylated sugars may be converted into their lactones. 

Sephton was the first to apply trimethylsilylation to the analysis of the products obtained from a methylated xylan, and he demonstrated the excellent separation obtained in this way between 2- and 3-0-methyl-xylose. This discovery was significant, as these two compounds, for example, are not separable as alditol acetates, and thus this method has been utilized in the study of other xylans.  

In a model study on the methyl ethers of n-mannose, the 2,3,4,6-and 2,3,5,6-ethers, as well as the 2,5,6- and 3,5,6-tri-O-methyl-D-mannoses, were best distinguished as the trimethylsilyl derivatives of the free sugars, and Gray and Ballou used these derivatives in their examination of a mannan from Mycobacterium phlei. 

The methylated galactoses obtained from tamarack galactan were analyzed as the per (trimethylsilyl) derivatives by Jiang and Timell, and the same derivatives were used by Larsson and Samuelson in a study of a galacturonic acid anhydride. 3-O-Methyl-n-galactose has been estimated in the hydrolyzate of a fungal heteropolysaccharide by using trimethylsilyl derivatives.  

Gorin and Magus investigated the use of the trimethylsilyl derivatives of the methyl ethers of 2-deoxy-2-(methylamino)-D-glucose and the corresponding n-galactose compounds. 

---

Similar halogenations have been done on 2-lithio-l-phenylsulfonylindole[2], 2-Lithio-l-phenylsulfonylindole is readily converted to the 2-(trimethylsilyl) derivative[2,3]. 2-Trialkylstannylindoles can also be prepared via 2-lithio-indoles[4,5], 2-Sulfonamido groups can be introduced by reaction of a 2-lithioindole with sulfur dioxide, followed by conversion of the sulfinic acid group to the sulfonyl chloride with A-chlorosuccinimide[6]. 

Etherification. The reaction of alkyl haUdes with sugar polyols in the presence of aqueous alkaline reagents generally results in partial etherification. Thus, a tetraaHyl ether is formed on reaction of D-mannitol with aHyl bromide in the presence of 20% sodium hydroxide at 75°C (124). Treatment of this partial ether with metallic sodium to form an alcoholate, followed by reaction with additional aHyl bromide, leads to hexaaHyl D-mannitol (125). Complete methylation of D-mannitol occurs, however, by the action of dimethyl sulfate and sodium hydroxide (126). A mixture of tetra- and pentabutyloxymethyl ethers of D-mannitol results from the action of butyl chloromethyl ether (127). Completely substituted trimethylsilyl derivatives of polyols, distillable in vacuo, are prepared by interaction with trim ethyl chi oro s il an e in the presence of pyridine (128). Hexavinylmannitol is obtained from D-mannitol and acetylene at 25.31 MPa (250 atm) and 160°C (129). 

Conversion to acetates, trifluoroacetates (178), butyl boronates (179) trimethylsilyl derivatives, or cycHc acetals offers a means both for identifying individual compounds and for separating mixtures of polyols, chiefly by gas—Hquid chromatography (glc). Thus, sorbitol in bakery products is converted to the hexaacetate, separated, and determined by glc using a flame ionisation detector (180) aqueous solutions of sorbitol and mannitol are similarly separated and determined (181). Sorbitol may be identified by formation of its monobensylidene derivative (182) and mannitol by conversion to its hexaacetate (183). 

In the case of indazoles the reaction of indazole, 5-nitroindazole or 6-nitroindazole with glycosyl halides and mercury(n) cyanide gives exclusively 2-glycosylindazoles (670), (673) and (675) (7QJHC1435). Similarly, the reaction of 1-trimethylsilyl derivatives of indazole, 3-cyanoindazole, 4-nitroindazole, 5-nitroindazole and 6-nitroindazole with 2,3,5-tri-O-acetyl-D-ribofuranosyl bromide gives only, or preferentially, the 2-ribofuranosyl derivatives (670)-(674) 7QJHC117, 70JHC1329). 

Me3SiNHS020SiMe3, CH2CI2, 30°, 0.5 h, 92-98% yield. Higher yields of trimethylsilyl derivatives are realized by reaction of aliphatic, aromatic, and carboxylic hydroxyl groups with A, <9-bis(trimethylsilyl)sulfamate than by reaction with N,<9-bis(trimethylsilyl)acetamide. ... 

The irradiation of 2-trimethylsilylfuran (29) gave the corresponding ring-opening product 30 in 68% yield (Scheme 12) (83JA6316). Other trimethylsilyl derivatives showed the same behavior (Scheme 12). The allene 32, obtained starting from the furan 31, can be thermally converted into 2,4-ditrimethylsilylfuran (33). 

In recent years, trimethylsilyl protection has often been used for the methine proton of the acetylenic group because of the mild reaction conditions for desilylation. As a rule, the starting pyrazole trimethylsilyl derivative is mixed up, at room temperature, with a 2 A aqueous solution of NaOH, potash, or methanol solution in ammonia. 

DETERMINATION OF SUCROSE AS ITS TRIMETHYLSILYL DERIVATIVE USING GAS-LIQUID CHROMATOGRAPHY... 

For further conversions via the titanium derivative see Section D.l. 3.3.3.8.2.3. The complex of the trimethylsilyl derivative was subjected to an X-ray structure analysis6. 

O- and N-containing heterocyclic compounds Characteristic rearrangement ion of butyrates except methyl Dinitrotoluenes Trimethylsilyl derivatives... 

Double rearrangement of protonated carboxylic acids Trimethylsilyl derivatives [CH2OSi(CH3)3]... 

Hydrochloric acid in anhydrous methanol (1 4 volume ratio) has been used to desilylate the trimethylsilyl derivatives of ferrocene, ruthenocene, and os-mocene, the rate coefficients (lO5 ) being ferrocene (5.60, 4.08), ruthenocene (261, 182), and osmocene (104, 80.2) for 0.596 M and 0.477 M hydrochloric acid, respectively, (temperature not quoted)690. 

The alkyl chain distribution of the base alcohol in alcohol sulfates is easily determined by gas chromatography. However, alcohol sulfates and alcohol ether sulfates are not volatile and require a previous hydrolysis to yield the free alcohol. The extracted free alcohol can be injected directly [306] or converted to its trimethylsilyl derivative before injection [307]. Alternatively, the alcohol sulfate can be decomposed by hydroiodic acid to yield the alkyl iodides of the starting alcohols [308]. A preferred method forms the alkyl iodides after hydrolysis of the alcohol sulfate which are analyzed after further extraction of the free alcohol, thus avoiding the formation of hydrogen sulfide. This latter method is commonly used to determine the alkyl chain distribution of alcohol ether sulfates. 

Structural Identification of Isomeric O-Trimethylsilyl Derivatives of Some Hexuronic Acids, J. F. Kennedy, S. M. Robertson, and M. Stacey, Carbohydr. Res., 57 (1977) 205-214. 

The cyclisation of naphthyl propargyl ethers occurs efficiently under microwave irradiation leading to naphthopyrans, but naphthofurans are formed in the presence of base <96JCR(S)338>. The thermal rearrangement of naphthyl 3-trimethylsilylprop-2-ynyl ethers yields the 4-trimethylsilyl derivatives of naphthopyrans <96H(43)751>. 

Other compounds identified in caramels are di-D-fructose and poly(glycosyl) dianhydrides (DFAs). DFAs were found in caramels prepared from D-fructose, D-glucose, and sucrose. The analysis was done after derivatization as TMS (per-0-trimethylsilyl) derivatives or as TMS-oxime (per-O-trimethylsilyl oxime) by... 

As an alternative, Harpp and coworkers reacted benzenesulfinyl chloride with the trimethylsilyl derivative of menthol to form the diastereomeric esters in 91% yield the epimer of configuration R could be isolated by crystallization in unspecified yield. Grossert and coworkers prepared ester 19 in 51% yield as a mixture of diastereomers by treating p-toluenesulfonyl chloride with sodium p-toluenesulfinate in DMF containing menthol. It was postulated that initial nucleophilic attack by the sulfinate oxygen on the sulfonyl sulfur atom gave the mixed sulfonate-sulfinate anhydride 21, which then reacted... 

---