Trimethyl silyl ether

The distillate was dissolved in a mixture of 350 ml of dry diethyl ether and 45 g of dry triethylamine (dried over powdered KQH). Trimethylchlorosilane (45 g) was added in 20 min with cooling at about 10°C. After standing for 1 h at room temperature the precipitate was sucked off on a dry sintered-glass funnel and rinsed with pentane. The filtrate was concentrated in a water-pump vacuum- The small amount of salt which precipitated during this operation was removed by a second suction filtration. Subsequent distillation afforded the trimethyl silyl ether, b.p. 100°C/15 mmHg, 1.4330, in 944 yield. 

Silyl Ethers. The preparation of per- O-trimethyl silyl ethers of sucrose is generally achieved by reaction with chi orotrimethyl sil ane and/or hexamethyldisila2ane in pyridine (25,26). However, this reaction is not selective and in general per-trimethyl silyl ethers are only used as derivatives for gas chromatographic studies. 

In a formal synthesis of fasicularin, the critical spirocyclic ketone intermediate 183 was obtained by use of the rearrangement reaction of the silyloxy epoxide 182, derived from the unsaturated alcohol 180. Alkene 180 was epoxidized with DMDO to produce epoxy alcohol 181 as a single diastereoisomer, which was transformed into the trimethyl silyl ether derivative 182. Treatment of 182 with HCU resulted in smooth ring-expansion to produce spiro compound 183, which was subsequently elaborated to the desired natural product (Scheme 8.46) [88]. 

Deprotection of trimethyl silyl ether has also been accomplished (88-100%) on K 10 day [43] or oxidative deavage (70-95%) in presence of day and iron(III) nitrate [44]. 

Keller S, Jahreis G (2004) Determination of underivatised sterols and bile acid trimethyl silyl ether methyl esters by gas chromatography-mass spectrometry-single ion monitoring in faeces. J Chromatogr Analyt Technol Biomed Life Sci 813 199-207... 

Trimethylsilyl ethers and esters.i The reaction of alcohols and allyltrimethyl-silane in acetonitrile with TsOH as catalyst (70 80°, 1 3 hours) results in trimethyl-silyl ethers in 85-95% yield with elimination of propene. The same reaction with carboxylic acids results in trimclhylsilyl esters. Phenols do not undergo this reaction. 

The naturally occurring amino acids are very polar, and cannot be separated as the free compounds by GC at a temperature below decomposition. If the polar groups in the molecule are chemically modified to produce a more volatile derivative a suitable temperature is then possible. Weinstein (25) reviews all the various derivatives which may be formed from amino acids and the GC conditions necessary to separate them. In actual practice only three derivatives are in popular use. These include the N-heptafluorobutyryl n-propyl ester derivatives, the N-trimethyl-silyl ether derivatives, and the n-trifluoroacetyl n-butyl ester derivatives. 

In some cases it may be desirable to block a particular functional group so as to direct lanthanide association to another site. A comparison of the effect of blocking binding at hydroxyl groups by preparing trifiuoroacetate, ferf-butyldimethylsilyl ether and trimethyl silyl ether derivatives was reported. The ferf-butyldimethylsilyl ether derivative was most effective at blocking lanthanide association. 

The TBS ether protecting group is more stable to hydrolysis than the trimethyl-silyl ether by a factor of 10" but is still readily cleaved by exposure to either n-Bu4NF in THF, HF-pyridine, CsF in DMF, or H2SiFg. Diisobutylaluminum hydride is another reagent for the deprotection of r-butyldimethylsilyl ethers under mild conditions. 

Smith and Stocklinski studied the metabolites of apomorphine (apocodeine, isoapo-codeine, norapocodeine) in urine and faeces of rats, and worked out a method for the determination of apomorphine as trimethyl silyl ether and the metabolites as free bases on an 0V-173% column. Average recovery of apocodeine and isoapocodeine was between 85 and 90 % for 500-1000 vg. 

Holmstedt et al. found that terminal primary amines condense readily with acetone, therefore a phenolic amine (serotonine) gives the corresponding trimethyl silyl ether-acetone condensation product when silylation is carried out in acetone solution. Primary amines may be entirely lost on a NGS column, but the acetone condensation products have a normal behaviour under these conditions. The relative retention times for indole bases related to tryptamine are summarized in Table 17.1. 

Acetone condensation product of serotonin 8.74 Trimethyl silyl ether of acetone condensations product ... 

Enzymatic synthesis from plant extracts. TMS=trimethyl silyl ether. 

The residue is dissolved in 2 ml of redistilled tetrahydrofuran (THF) containing 10 mg per 100 ml of coprostan-3 -ol (COP) as internal standard. (Blowout pipettes must not be used because moisture is detrimental to the formation of trimethyl silyl ethers.) The solution is transferred by capillary pipette to a 15-ml conical centrifuge tube, and the flask is rinsed out with 0.5 ml of fresh THF. Hexamethyldisilazane (0.3 ml) and trimethylchlorosilane (0.1 ml) are added. The tube is then stoppered, thoroughly mixed, and allowed to stand at room temperature overnight. 

Aldol reaction. Catalyzed by Tf2NH, the Mukaiyama aldol reaction of tris(trimethyl-silyl) ethers of enolized ketones affords products that react with Grignard reagents diasteieoselectively. 

A sensitive method for the detection and separation of micro quantities of cyclic acetals of sugars by means of gas-liquid, partition chromatography has been described by Jones and coworkers. The column packing consisted of an intimate mixture of Apiezon M grease on Cromosorb W and butanediol succinate polyester on Cromosorb W, which was packed on top of a column of SE-30 methylsilicone polymer and glass beads. The column temperatme was maintained at 200°. Some cyclic acetals of sugars have been fractionated by gas-liquid chromatography as their (trimethyl-silyl) ethers. These derivatives are conveniently prepared and the method is especially suited to the less volatile monoacetals. 

Cyclization by tandem Michael-Dieckmann reaction. Ring construction from compounds with juxtaposed ketone (or ester) and conjugated ester groups is made easy. It is rendered irreversible by trapping the alkoxide ion as a trimethyl-silyl ether. 

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