Ethers trimethylsilyl

The presence of 2,3,4- and 2,4,6-tri-O-methyl-D-mannoses had been overlooked in earlier work in which the separation of the methyl mannosides had been attempted on Apiezon M. When the methyl glycosides were separated as their trimethylsilyl ethers on Carbowax 6000, resolution of the 2,3,4, 2,4,6, and 3,4,6 isomers was achieved. Bauer and coworkers have continued with the application of this method in their work on yeast mannans. 

Bhattacharjee and Gorin utilized trimethylsilyl derivatives of methyl maimosides in a model study on mannose ethers, and recommended these compounds for the separation of the dimethyl isomers in particular. Handa and Montgomery likewise used trimethylsilyl ethers in a study of the partial methylation of methyl a-o-mannopyranoside, and Choy and Unrau gave similar data for 2,3,6- and 2,4,6-tri-O-methyl-n-mannose. 

Gorin and coworkers applied this type of separation in work on yeast galactomannans and mannans, as have Srivistava and coworkers in examining a galactomannan from Sesbania grandifiora. 

In a study on the vinylation of methyl cD glucopyranoside, it was found that silylation of the O-vinylglucosides caused decomposition but, after reduction, the resulting ethyl ethers were successfully s arated as the trimethylsilyl ethers of the methyl 0-ethylglycosides.  

The problem of similar retention-times occurs not only with isomeric compounds but also in mixtures containing deoxy sugars. Thus, 2,3-di-O-methyl-L-rhamnose and 2,3,4,6-tetra-O-methyl-n-glucose are inseparable as their methyl glycosides, but, after trimethylsilylation of the mixture, resolution is readily achieved, the rhamnoside being eluted first. Larsson and Samuelson used the same principle in a study of the structure of an 0-(a-D-galactopyranosyluronic add)-L-rhamnopyranose 1,2 -r,2-dianhydride. 

Methanolysis of polysaccharides as an alternative to hydrolysis has been discussed in Section II (see p. 14). In brief, this method of depolymerization may be more convenient with glycolipids, because the fatty acids are simultaneously obtained as their methyl esters, and aminodeoxyhexoside bonds are more readily methanolyzed than hydrolyzed. An additional advantage is the increased stability of 

Several model studies on the separation of monosaccharides as their methyl glycosides have been published. These include three related papers, by Hough and coworkers,88,364,365 concerned with the determination of D-galactose, D-mannose, and L-fucose, and applied to membrane glycoproteins.366 Their method was also used in examining 

Trimethylsilyl ethers of methyl glycosides have been used in analyzing bacterial endotoxins that contain 3,6-dideoxyhexoses, and, because of the volatility of such glycosides, careful temperature-programming is essential.373 Methyl D-glucosides and analogs have been 

Trimethylsilylation has been used in studying the methanolysis of monosaccharides383,384 and the products obtained by reduction of 4-deoxyuronic acids.385 Various natural phenolic glycosides have been separated as trimethylsilyl ethers,386 as have glucosinolates.126 

Yoshida and coworkers387 have compared the retention times of 41 furanosides and pyranosides of D-glucose, D-galactose, D-mannose, and D-glucuronic acid as their O-trimethylsilyl, O-acetyl, and O-tri-fluoroacetyl derivatives. 

---

To a solution of 0.25 mol of the trimethylsilyl ether in 120 ml of dry diethyl ether was added in 20 min at -35°C 0.50 mol of ethyllithium in about 400 ml of diethyl ether (see Chapter II, Exp. 1). After an additional 30 min at -30°C the reaction mixture was poured into a solution of 40 g of ammonium chloride in 300 ml of water. After shaking, the upper layer was separated off and dried over magnesium sulfate and the aqueous layer was extracted twice with diethyl ether. The ethereal solution of the cumulenic ether was concentrated in a water-pump vacuum and the residue carefully distilled through a 30-cm Vigreux column at 1 mmHg. The product passed over at about 55°C, had 1.5118, and was obtained in a yield of 874. Distillation at water-pump pressure (b.p. 72°C/I5 mmHg) gave some losses due to polymerization. 

The most stable protected alcohol derivatives are the methyl ethers. These are often employed in carbohydrate chemistry and can be made with dimethyl sulfate in the presence of aqueous sodium or barium hydroxides in DMF or DMSO. Simple ethers may be cleaved by treatment with BCI3 or BBr, but generally methyl ethers are too stable to be used for routine protection of alcohols. They are more useful as volatile derivatives in gas-chromatographic and mass-spectrometric analyses. So the most labile (trimethylsilyl ether) and the most stable (methyl ether) alcohol derivatives are useful in analysis, but in synthesis they can be used only in exceptional cases. In synthesis, easily accessible intermediates of medium stability are most helpful. 

With appropriately substituted oxetanes, aluminum-based initiators (321) impose a degree of microstmctural control on the substituted polyoxetane stmcture that is not obtainable with a pure cationic system. A polymer having largely the stmcture of poly(3-hydroxyoxetane) has been obtained from an anionic rearrangement polymerisation of glycidol or its trimethylsilyl ether, both oxirane monomers (322). Polymerisation-induced epitaxy can produce ultrathin films of highly oriented POX molecules on, for instance, graphite (323). Theoretical studies on the cationic polymerisation mechanism of oxetanes have been made (324—326). 

Polarimetric analysis of sorbitol and mannitol in the presence of each other and of sugars is possible because of their enhanced optical rotation when molybdate complexes are formed and the higher rotation of the mannitol molybdate complex under conditions of low acidity (194). The concentration of a pure solution of sorbitol may be determined by means of the refractometer (195). Mass spectra of trimethylsilyl ethers of sugar alcohols provide unambiguous identification of tetritols, pentitols, and hexitols and permit determination of molecular weight (196). 

Me3SiNEt2- Trimethylsilyldiethylamine selectively silylates equatorial hydroxyl groups in quantitative yield (4-10 h, 25°). The report indicated no reaction at axial hydroxyl groups. In the prostaglandin series the order of reactivity of trimethylsilyldiethylamine is Cii > Ci5 C9 (no reaction). These trimethylsilyl ethers are readily hydrolyzed in aqueous methanol containing a trace of acetic acid. The reagent is also useful for the silylation of amino-acids. ... 

Trimethylsilyl ethers are quite susceptible to acid hydrolysis, but acid stability is quite dependent on the local steric environment. For example, the 17o -TMS ether of a steroid is quite difficult to hydrolyze. 

Aryl and alkyl trimethylsilyl ethers can often be cleaved by refluxing in aqueous methanol, an advantage for acid- or base-sensitive substrates. The ethers are stable... 

Trimethylsilyl ethers are readily cleaved by fluoride ion, mild acids, and bases. If the TMS derivative is somewhat hindered, it also becomes less susceptible to cleavage. A phenolic TMS ether can be cleaved in the presence of an alkyl TMS ether [Dowex lX8(IfO ), EtOH, rt, 6 h, 78% yield]. ... 

Phenyl-10-oxo)anthryl Ether (Tritylone) 43. Trimethylsilyl Ether (TMS)... 

Cyanohydrin trimethylsilyl ethers are generally useful as precursors of ctir-bonyl anion equivalents and as protected forms of aldehydes. Direct conversion of p-anisaldehyde into 0-TRIMETHYLSILYL-4-METH0XYMANDEL0-NITRILE employs a convenient in situ generation of trimethylsilyl cyanide from chlorotnmethylsilane A general synthesis of allemc esters is a variant of the Wittig reaction. Ethyl (triphenylphosphoranylidene)acetate converts pro-pionyl chloride into ETHYL 2,3-PENTADlENOATE. 

Trimethylsilyloxy-3-penten-2-one cis) (acetylacetone enol trimethylsilyl ether) [13257-81-3 M 172.3, b 66-68"/4mm, 61-63"/5mm, d4 0.917, Up 1.452. Fractionally distilled and stored in glass ampoules which are sealed under N2. It hydrolyses readily in contact with moisture giving, as likely impurities, hexamethyldisiloxane and 2,4-pentanedione. [J Am Chem Soc 80 3246 795S.]... 

Aryl and alkyl trimethylsilyl ethers can often be cleaved by refluxing in aqueous methanol, an advantage for acid- or base-sensitive substrates. The ethers are stable to Grignard and Wittig reactions and to reduction with lithium aluminum hydride at —15°. Aryl -butyldimethylsilyl ethers and other sterically more demanding silyl ethers require acid- or fluoride ion-catalyzed hydrolysis for removal. Increased steric bulk also improves their stability to a much harsher set of conditions. An excellent review of the selective deprotection of alkyl silyl ethers and aryl silyl ethers has been published. ... 

A solution whieh eontained ca. 95% of the O-deuterated 3-hydroxyfuran 22 was generated from the trimethylsilyl ether in [De]-DMS0/D20 with DCl at 32°C. After several hours it was eonverted into the keto tautomer 23 deulerated at position 2 (Seheme 9). In all solvents used (CCI4, [DgjDMSO, [Dg]aeetone, CD3OD) no detectable amount of the enol was present at equilibrium (89JA5346). 

The 0,N-dideuterated enol was formed by hydrolysis of the O-trimethylsilyl ether 123 (R = TMS) (in 80% [D6]DMSO/20% D2O with 5. lO " M DCl). N-Methylindoxyl (formed by hydrolysis of its acetate) exists in the solid state as a mixture of the enol and the keto tautomers (34% enol/66% keto). The NMR spectrum of freshly prepared solution in DMSO demonstrated signals of both enol and keto forms. However, at equilibrium (reached in 18 h at RT) the ratio of enol to ketone depends strongly on the polarity of the solvent used thus, in [Dg]DMSO the tautomeric mixture contains 92% enol, while in CDCI3 the keto form predominates (97%). A solution with 100% enol could be generated by hydrolysis of its O-trimethylsilyl ether [conditions 80% [Dfi]DMSO/20% D2O with 5 10" M DCl at 32°C (86TL3275 87PAC1577 88TL250)]. 

A mixture of d- and l- hexoses also results from the hydroboration of these 5-enes. Hydroboration results in anti-Markownikoff, cw-hydration of the double bond and the amount of each hexose formed varies according to the nature of the substituent groups. For example, hydroboration (23) of methyl 6-deoxy-a-D-ryZo-hex-5-enopyranose (3) affords methyl a-D-glucopyranoside and methyl / -L-idopyranoside in the ratio of 1 2.5 respectively whereas hydroboration of the fris-trimethylsilyl ether of 3 afforded them in the ratio 1 0.6 respectively. The hydroboration method can be used to achieve specific labelling of hexoses with tritium methyl-/ -L-idopyranoside[5-H3] and methyl a-D-glucopyranoside [5-H3] were thus prepared (23). Similarly, hydroboration of the D-Zt/ro-hex-5-eno derivative (14) with diborane-H3 followed by removal of the isopropyli-dene group, afforded methyl a-D-mannopyranoside [5-H3] and methyl / -L-gulopyranoside [5-H3] in the ratio of 1 2 respectively (23). 

Acetals are useful because they can act as protecting groups for aldehydes and ketones in the same way that trimethylsilyl ethers act as protecting groups for alcohols (Section 17.8). As we saw previously, it sometimes happens that one functional group interferes with intended chemistry elsewhere... 

Thymine, electrostatic potential map of, 1104 structure of, 1101 Thyroxine, biosynthesis of, 551 structure of. 1020 TIme-of-flight (TOP) mass spectrometry, 417-418 Titration curve, alanine, 1023 TMS, see Tetramethylsilane see Trimethylsilyl ether Tollens reagent, 701 Tollens test, 992... 

Trichloroacetic acid, pKa of. 759 Trifluoroacetic acid, pKa of, 756 Trifluoromethylbenzene, electrostatic potential map of, 565 Triglyceride, see Triacylglycerol, 1061 Trimethylamine, bond angles in, 919 bond lengths in, 919 electrostatic potential map of, 921 molecular model of, 919 Trimethylammonium chloride, IR spectrum of, 953 Trimethylsilyl ether, cleavage of, 627-628... 

Notes, fa) Rate of metallation with t-BuLi varies from case to case. Lithiation of ally] alcohol trimethylsilyl ether proceeds to completion in 2 h at -78 °C, whereas the corresponding methallyl derivative requires 3.5 h at -33°C. 

Cleavage of trimethylsilyl ethers to the parent alcohols occurs quite readily on exposure to nucleophiles such as methanol, especially in the presence of... 

---