Silyl derivatives

Derivatives of this type are widely used in gas chromatography to obtain volatile derivatives of involatile compounds. Silyl derivatives, e.g., for the case of the TMS group donor, can be obtained in accordance with the following scheme  

When silyl derivatives are obtained, as a rule all of the functional groups of a molecule form the corresponding derivatives in one stage. Methods used to obtain silyl derivatives are discussed in detail in a book by Pierce [122] and in a review by Drozd [57], and those used for trimethylsilyl derivatives in a review by Miller and Pacakova [123]. 

Various reagents, some of which are listed in Table 1.4, are used to obtain silyl derivatives. 

For the protection of the carboxyl group methods are used that result in the formation of esters. Those used most frequently are the following. 

The ester is formed in accordance with the following reaction  

COMPARISON OF THE CHROMATOGRAPHIC PROPERTIES OF SOME ACYL DERIVATIVES OF AMINES [74] 

Conditions (A) 6 ft. x 4 mm I.D. glass column 6% QF-1 on Anakrom ABS, 60-70 mesh column temperature, 152°C carrier gas (nitrogen) flow-rate, 30 ml/min (B) column as in A temperature 155°C carrier gas (nitrogen) flow-rate, 80 ml/min. 

Amine Derivative Conditions Retention Peak Sensitivity of 

Problems with the selection of the stationary phase for the GC of acyl derivatives are similar to those associated with the GC of esters. In simple separations silicone and polyester phases are satisfactory but more complicated separations require special phases, low coatings, mixed phases, etc. Individual cases are discussed for specific types of compounds in Chapter 5. 

Many methods for the preparation of TMS derivatives have been developed. Pierce [77] reported a number of methods and their modifications depending on the type of substrate to be silylated. Commercial reagents prepared for immediate use are available. Mixtures of reagents with solvents are supplied for methods elaborated for individual substrates. Individual types of reagents can be classified into four groups (see Table 4.8)  

Another class of widely employed protecting groups is represented by silyl ethers [38, 39, 62-64],The trimethylsilyl (TMS) moiety was the silyl group originally employed [63,64], but because of the low stability of TMS ethers in acidic or basic media [66,67], many other silyl derivatives are nowadays preferred in synthetic organic chemistry. 

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Metals and Metal Derivatives, Silane reacts with alkah metals dissolved in various solvents, forming as the chief product the silyl derivative of the metal, potassium being the most commonly studied, eg, KSiH [13812-63-OJ (27—30). When 1,2-dimethoxyethane or bis(2-methoxyethyl)ether are used as solvents, two competing reactions occur, where M is an alkah metal. 

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). 

Silyl-derived protective groups are also used to mask the thiol function. A complete compilation is not given here since silyl derivatives are described in the section on alcohol protection. The formation and cleavage of silyl thioethers proceed analogously to simple alcohols. The Si—S bond is weaker than the Si—O bond, and therefore sulfur derivatives are more susceptible to hydrolysis. For the most part silyl ethers are rarely used to protect the thiol function because of their instability. Silyl ethers have been used for in situ protection of the — SH group during amide formation. ... 

Alkyldithio carbamates are prepared from the acid chloride (Et N, EtOAc, 0°) and amino acid, either free or as the O-silyl derivatives (70-88% yield). The N- i-propyldithio) carbamate has been used in the protection of proline during peptide synthesis. Alkyldithio carbamates can be cleaved with thiols, NaOH, Ph P/TsOH. They are stable to acid. Cleavage rates are a function of the size of the alkyl group as illustrated in the table below. 

An excellent review is available that discusses the selective cleavage of numerous silyl derivatives. ... 

These groups, along with a number of other trialkylsilylethyl derivatives, were examined for protection of phosphorothioates. Only the phenyl-substituted silyl derivative was useful, because simple trialkylsilyl derivatives were prone to acid-catalyzed thiono-thiolo rearrangement. Other trialkylsilylethyl derivatives also suffer from inherent instability upon storage,but the trimethylsilylethyl group has been used successfully in the synthesis of the very sensitive agrocin 84 and for intemucleotide phosphate protection with the phosphoramidite approach. 

Replacement of heterocyclic rings in nucleosides by ring systems which do not occur in nature represents another approach to compounds which may have activity against viral and neoplastic diseases. One of the early successes in this category involves replacement of a pyrimidine ring by a triazine. The synthesis starts with a now classical glycosidation of a heterocycle as its silylated derivative (146) with a protected halosugar (145), in this case a derivative of arabinose... 

Note. Anhydrous reaction conditions are generally essential since the silylated derivatives are sensitive to water in varying degrees. 

Wholly aromatic hyperbranched polyesters based on 3,5-dihydroxyisophthalic acid can be prepared either from bis(acetoxy)isophthalic acid or from its silylated derivative (Scheme 2.67). 

The hemiacetal 54 adsorbed on water-saturated silica gel gives, by MW irradiation, a 1 1 mixture of cycloadducts isolated as silyl derivatives 55 and 56. The water is probably necessary for the success of the reaction because (i) it is an efficient generator of heat in the MW process, (ii) it accelerates the cycloaddition by hydrophobic effect, and (iii) it facilitates the hemiacetal-hydroxyketone equilibrium which furnishes the dienophile moiety for the cycloaddition [42]. 

The predictions of the reactivities by the geminal bond participation have been confirmed by the bond model analysis [103-105] of the transition states and the calculations of the enthalpies of activation AH of the Diels-Alder reaction [94], the Cope rearrangement [95], the sigmatropic rearrangement [96], the Alder ene reaction [100], and the aldol reaction [101] as are illustrated by the reactions of the methyl silyl derivatives in Scheme 38 [102], The bond is more electron donating than the bond. A silyl group at the Z-position enhances the reactivity. 

The stable P-unsubstituted phosphinous amide H2PN(SiMe3)2 has been shown to suffer the nucleophilic displacement of the disilazane moiety by the action of thiols R-SH giving the phosphinous thioesters R-S-PH2 [13]. For the sake of brevity we shall not comment on other relevant reactions of AT-silyl phosphinous amides, such as the anionic P-silylation [115] and P-alkylation [22], the consecutive dialkylation of PH derivatives [18] and the fluorodesily-lation of P-fluoro-JV-silyl derivatives [140]. 

Silicon-transition metal chemistry is a relatively new area. The work of Hein and his associates (1941) on Sn—Co derivatives established the possibility of forming bonds between a Group IVB metal and a transition element 139), but it was another fifteen years before CpFe(CO)2SiMej 203), the first of many silyl derivatives, was synthesized. The interest in these compounds derives from (1) comparison with the corresponding alkyl- and Ge-, Sn-, and Pb- transition metal (M) complexes, including the role of ir-back-bonding from filled d orbitals of M into empty d orbitals on Si (or other Group IVB metal), and (2) expectation of useful catalytic properties from such heteronuclear derivatives. 

Succinimide is readily silylated by HMDS 2 to the N-silylated product 201, which seems, however, to be in equilibrium with the O-silylated derivative 202 a (cf the closely related reactive center in persilylated uridine 3) and reacts after 6-10 days at 24 °C with one equivalent of primary or secondary amines such as morpholine to give the crystalline colorless cyclic acylamidine 203 and HMDSO 7, even in the absence of any protective gas [33] (Scheme 4.12). The reaction is much faster on heating to 120 °C under argon. At these temperatures 201 and 202 a, and possibly also the acylamidine 203, are apparently partially O-silylated by HMDS 2 to the very sensitive 2,5-bis(trimethylsilyloxy)pyrrole 202b or to 2-tri-... 

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