Trimethylsilyl TMS Derivatives

For gas chromatography and mass spectrometry, the addition of the TMS group(s) to polar compounds confers thermal and chemical stability in addition to enhanced volatility. Although dimethylsilyl ether derivatives are more volatile, they lack the chemical stability required for routine application [1]. The properties of the most commonly used reagents for trimethylsilylation are given below. 

BSTFA is the most widely used reagent for trimethyl-silylation. The reagent was first prepared by Stalling et al. [29], and is now available from a large number of proprietary sources, both as the pure compound and mixed with catalysts, commonly TMCS. Other catalysts that have been used with BSTFA include trifluoroacetic acid [30, 31], hydrogen chloride [32], potassium acetate [33, 34], piperidine [35, 36], O-methylhydroxylamine hydrochloride [37] and pyridine [31, 38]. Pyridine is especially useful as a solvent on account of its ability 

When derivatization does not proceed smoothly, the use of a suitable solvent can help to produce efficient silylation. As with BSTFA, the addition of TMCS (usually 1-20%) as catalyst helps to enhance the effectiveness of silylation. Although silylation reactions involving BSA are normally carried out under anhydrous conditions, it has been found that the presence of 1% of water can substantially increase the reaction rate [41, 42]. This catalytic activity was thought not to be due directly to the water, but to the trimethylsilanol formed by hydrolysis of the BSA [41]. Other catalysts that have been used with BSA include oxalic acid [43], trifluoro-acetic acid [30], hydrochloric acid [44], potassium acetate [33] and trimethylbromosilane [45]. The use of BSA together with other silylating reagents is discussed below in Section 4.1.8. 

BSA was first reported by Birkofer ef al. in 1963 [40). It is a more potent TMS donor than HMDS or TMSDEA (see below) and is one of the most commonly used silylating reagents. The reactivity of BSA is similar to that of BSTFA and MSTFA (see below), readily silylating non-sterically hindered alcohols, carboxylic acids, amino acids, amides, amines and enols. Although not as volatile as the by-products of silylation using BSTFA, those of BSA (N-trimethylsilylacetamide and acetamide) are sufficiently volatile not to interfere in the majority of GC analyses. 

TMCS was one of the first silylation reagents prepared [61]. Although continuing to find wide use in synthetic chemisty, TMCS is rarely used alone in analytical applications. The common analytical use of TMCS is in mixtures, e.g. HMDS/TMCS/pyridine or BSA/TMSIM/ TMCS, which function as very powerful broad-spectrum silylation reagents (see below). The role of TMCS as a silylation catalyst is well recognized, as already mentioned. The facile reaction of TMCS with F ions has found application to the determination of fluorides in air, exhaust gases, bone ash and water [62]. The use of TMBS and TMIS as silylation catalysts has been discussed briefly above their analytical use is discussed below in the appropriate sections. 

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Trimethylsilyl (TMS) derivatives in organic synthesis, 22 695-696 as silylating agents, 22 694 Trimethylsilyl azide, as silylating agent, 22 695-696... 

The advantage of trimethylsilyl (TMS) derivatives lies in the simplicity of the derivatization procedure, which is carried out by the addition of N,0-bis(trimethylsilyl)trifluoroacetamide (BSTFA) in acetonitrile and heating for approximately 2 h at 150 °C under anhydrous conditions in a sealed tube. However, there may be problems owing to the formation of multiple derivatives of each amino acid. Another technique involves the formation of n-butyl esters of the amino acids and their subsequent trimethylsilylation by a similar procedure. The n-butyl esters are formed by heating the amino acids for 15 min in n-butanol and HC1 and these are then converted to the A-TMS-n-butyl ester derivatives. A-acyl amino acid alkyl esters are commonly used. Acetylation of the butyl, methyl or propyl esters of amino acids,... 

Dwell time, or the time the molecule was actually in the lamp unit, and concentration were two parameters that affected the rate of degradation. Mass spectra of the trimethylsilyl (TMS) derivatives of atrazine subjected to UV-ozonation revealed a number of dehalogenated, dealkylated s -triazines, paraquat yielded the 4-picolinic acid, and 2,4-D gave oxalic acid, glycolic acid and several four-carbon oxidation products. The economics of UV-ozonation as a pretreatment for land disposal compares favorably with incineration and other options open to the small pesticide user. 

An example of gas chromatogram for the trimethylsilyl (TMS) derivative of alkali-hydrolyzed TTX is shown in Figure 4. Although a variety of peaks are seen in this chart, only the peak with a retention time of 7.8 min is associated with C -base-(TMS), as evidenced by mass spectroscopy (Figure 5). 

Determination of the monosaccharide composition by gas chromatography of alditol acetates is commonly used for cell wall analyses because the procedure gives a single peak for each sugar. An alternative is to prepare trimethylsilyl (TMS) derivatives. However, these are easily hydrolyzed by moisture in the atmosphere and therefore should be analyzed in the gas chromatograph immediately, whereas alditol acetates are relatively more stable and could be rerun on the gas chromatograph the following day if required. 

GC and thin layer chromatography (TLC) are used less frequently than HPLC for the analysis of flavonols.79-90 104 To accomplish analysis by GC, flavonols must first be hydrolyzed and converted into trimethylsilyl (TMS) derivatives to increase their volatility and thermal stability. Although this method provides high resolution and low detection limits, it should be noted that TMS derivatives can form with more than one hydroxyl group as they possess different reactivities. This often results in the production of several derivatives, which can complicate quantification. Thus, the... 

Identification and quantification Two spectral user-libraries (MS and MS/MS) were developed using injections of TMS-derivatized authentic reference compounds. The MS library recorded the retention times and normal El mass spectra of trimethylsilyl (TMS) derivatives of authentic standards under the chosen chromatographic conditions, while the MS/MS library recorded retention times and product ion spectra derived from the specifically chosen precursor ions (Table 7.3) of TMS... 

Fig. 6.1.3. Trimethylsilyl (TMS) derivatives of l-hydroxy-3-(4-hydroxy-3-methoxyphenyl)-2-propanone (Ja., Fig. 6.1.1)...

The synthesis of these nucleosides was achieved using a silylation procedure. Trimethylsilyl (TMS) derivatives of agroclavine, lysergene, elymoclavine-0-acetate, lysergol-O-acetate and 9,10-dihydrolysergol-O-acetate were prepared from N-methyl-N-(trimethylsilyl)-trifluoroacetamide in MeCN [33]. The TMS derivatives were then treated with l-0-acetyl-2,3,5-tri-0-benzoyl-)3-D-ribo-furanose. From the different reaction conditions tested, the best involved... 

The structure of anandamide was established by mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy. Additional data wereobtained from the GC-MS and CID measurements of the trimethylsilyl (TMS) derivative of the material. The results suggest that anandamide is an ethanolamide of a tetraenic C20 fatty acid. 

A range of reagents, with differing degrees of reactivity, are commonly available to make trimethylsilyl (TMS) derivatives. The silylating potential can be increased by the choice of an appropriate solvent (e.g., pyridine, DMF, acetonitrile) or by the addition of a catalyst (e.g., 1-20% TMCS).22 127... 

FIGURE 2.5 Partial GC chromatograms showing the separation of G and S thioacidolysis monomers (compounds 2-5 outlined in Figure 2.4 and analyzed as their trimethylsilylated [TMS] derivatives) recovered from (a) a one-year-old control poplar tree and (b) a one-year-old transgenic poplar tree severely depressed in COMT activity. (Based on Jouanin, L., Goujon, T., de Nadai, V., Martin, M.T., Mila, I., Vallet, C., Pollet, B., Yoshinaga, A., Chabbert, B., Petit-Conil, M., and Lapierre, C., Plant physiol., 123, 1363-1373, 2000.)... 

This paper (S4) compares the two silylating reagents bis (trimethyl-silyl) acetamide (BSA), first described by Klebe et ad. (K6), and bis-(trimethylsilyl) trifluoroacetamide (BSTFA), for the preparation of volatile trimethylsilyl (TMS) derivatives of 12 sulfur-containing amino acids. BSTFA was recommended as the reagent of choice for taurine, cysteic acid, homocystine, djenkolic acid, ethionine, methionine sulfone, L-2-thiolhistidine, cysteine, and cystine. For S-methyl-L-cysteine, methionine sulfoxide, and methionine, BSA was used as silylating reagent. 

Using bis (trimethylsilyl) acetamide (BSA), volatile trimethylsilyl (TMS) derivatives of the active components 3,5,3, 5 -tetraiodothyronine (thyroxin, TJ and 3,5,3 -triiodothyronine (T3) have been prepared as well as TMS derivatives of the nonphysiologically active components 3,3, 5 -triiodothyronine (T3 ), 3,5-diiodothyronine (T2), and 3,5-diiodo-tyrosine (DIT). Separation and quantitative estimation of these iodinated amino acids is achieved by gas-liquid chromatography. The method is... 

Fig. 1.7 shows two chromatograms of (A) compounds 1 and 2 and (B) their trimethylsilyl (TMS) derivatives obtained by treatment with N,0-bis(trimethylsilyl)acetamide (BSA). Separation was performed on a glass capillary column (3.5 m x 0.25 mm I.D.) with SE-30 as the stationary phase at 200°C. The initial compounds are not separated on a non-polar stationary phase under these conditions, but their TMS derivatives are separated satisfactorily, with the time necessary for separation decreasing approximately two-fold. 

Trimethylsilyl (TMS) derivatives are frequently used for GC-MS analysis of plant hormones. Both TMS esters and ethers are formed, but when the compound of interest has both carboxyl and hydroxyl groups, samples are often methylated prior to silylation. TMS derivatives are degraded rapidly by moisture so it is essential to ensure that samples and reagents are dry. Because of their sensitivity to water, TMSi derivatives cannot be purified readily prior to analysis. 

The EtOAc-soluble fraction of the alkaline hydrolysate of 37 containing a mixture of fatty acid units was treated with ozone followed by NaBH4 reduction. Trimethylsilyl (TMS) derivatives of the ozonolysis product were subjected to chiral CjC analysis (Chirasil-Val) to give a p identical with the TMS-derivative of (i0-l 2-propanediol. Consequently, the absolute configuration of C-9 " position of 37 was assigned as S. 

We examined a number of commercial blackbery juice concentrates by GLC of their trimethylsilyl (TMS) derivatives. Three samples were found to contain from 2.8-21.5 of total sugars as sorbitol ( ) leading us to believe that those samples were adulterated. Previously, we had examined lU authentic samples of blackberries by similar analytical procediires and no sorbitol was detected in any of those samples (6). Sorbitol is non-fermentative... 

Hedgley and Overend (151) were the first to study trimethylsilyl (TMS) derivatives of monosaccharides. The results were sufficiently en- ouraging to stimulate interest in these derivatives although, probably because of the high column temperatures initially used, the separations were not always satisfactory. Ferrier 119) improved the separation by operating at a lower temperature and Smith and Carlsson (294) assessed the potential of these derivatives for quantitative work. 

Trimethylsilyl (TMS) derivatives are among the most commonly used in GC-MS and are characterized by ease of formation, excellent GC properties [14] and useful mass spectrometric fragmentation (Figure 5a). In addition, many TMS derivative mass spectra are available as reference spectra in a number of available libraries [11, 15-20]. 

More importantly, some silylating reagents used for protection of functional groups with active hydrogen atoms can react with carbonyl fragments with the formation of trimethylsilyl (TMS) derivatives of enols. If such unpredictable mode of derivatization is undesirable, all carbonyl fragments should be protected before silylation, for example, by conversion into alkoxyimino groups (alkyl ethers of oximes, see below). 

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