Hexamethyldisilazane silylation

Unsubstituted thieno[2,3-d]pyrimidin-4(3//)-one 2a was converted into the trimethylsilyl derivative 137 by heating in hexamethyldisilazane. Silyl derivative 137 was alkylated at N-3 with l-0-acetyl-2,3,5-tri-O-benzoyl-/3-D-ribofuranose in the presence of stannic chloride in 1,2-dichloroethane or... 

Me3Si)2NH, Me3SiCl, Pyr, 20°, 5 min, 100% yield. ROH is a carbohydrate. Hexamethyldisilazane (HMDS) is one of the most common sily-lating agents and readily silylates alcohols, acids, amines, thiols, phenols, hydroxamic acids, amides, thioamides, sulfonamides, phosphoric amides, phosphites, hydrazines, and enolizable ketones. It works best in the presence of a catalyst such as X-NH-Y, where at least one of the group X or Y is electron-withdrawing. ... 

Intramolecular cyclization of 2-phenysulfonylmethyl lactam 3 took place upon reaction with lithium hexamethyldisilazan via generating its a-sulfonyl carbanion to give a cyclized postulated intermediate that can be quenched with trimethylchlorosilane to afford the stable silyl ketal 4. The later ketal was desulfonylated by Raney-Ni and desilylated through treatment with tetrabutyl ammonium fluoride (BU4NF) to afford the carbacephem 5 (94M71) (Scheme 1). 

The JV-silyl phosphinous amides present some particularities in their reactivity that make these compounds worth commenting on separately. They are stable and can be easily prepared in the usual way by reaction of AT-silyl substituted primary amines or hexamethyldisilazane with halophosphanes [48,49,128,129] or byJV-silylation of the appropriate phosphinous amides [72, 107]. The reductive Ph-P bond cleavage in AT-silyl phosphazenes Ph3P=NSiMe3 by the action of sodium is a peculiar example of preparing Ph2PNHSiMe3 [130]. 

Whereas silylations with trimethylchlorosilane (TCS) 14 (b.p. 57 °C) demand the presence of a base to neutralize the HCl evolved, giving rise to the hydrochloride of the base, the use of hexamethyldisilazane (HMDS) 2 (b.p. 126 °C), in particular in the presence of 0.01-0.05 equivalents of acidic catalysts such as TCS 14 or ammonium sulfate, should normally be preferred as the preparative silylating reagent, because HMDS 2 ... 

It should be noted here that the lithium salt of hexamethyldisilazane li-HMDS 492 (and Na-HMDS-(486) and K-HMDS in Sections 5.1.2 and 5.1.3), which is readily obtained on treatment of a solution of HMDS 2 in hexane or THF with butyUithium at -78 °C, is not only a very useful and selective strong base, e.g. for Wittig reactions, but can also add to carbonyl groups to yield the silylated Schiff bases or nitriles (cf. Sections 4.7 and 5.1.3) or to nitriles to afford N-silylated ami-dines. Alkylation of the Li-HMDS 492, e.g. with allyl bromide, affords, furthermore, N,N-bis(trimethylsilylated) primary amines such as 43 [64]. The combina-... 

General Considerations. The following chemicals were commercially available and used as received 3,3,3-Triphenylpropionic acid (Acros), 1.0 M LiAlH4 in tetrahydrofuran (THF) (Aldrich), pyridinium dichromate (Acros), 2,6 di-tert-butylpyridine (Acros), dichlorodimethylsilane (Acros), tetraethyl orthosilicate (Aldrich), 3-aminopropyltrimethoxy silane (Aldrich), hexamethyldisilazane (Aldrich), tetrakis (diethylamino) titanium (Aldrich), trimethyl silyl chloride (Aldrich), terephthaloyl chloride (Acros), anhydrous toluene (Acros), and n-butyllithium in hexanes (Aldrich). Anhydrous ether, anhydrous THF, anhydrous dichloromethane, and anhydrous hexanes were obtained from a packed bed solvent purification system utilizing columns of copper oxide catalyst and alumina (ether, hexanes) or dual alumina columns (tetrahydrofuran, dichloromethane) (9). Tetramethylcyclopentadiene (Aldrich) was distilled over sodium metal prior to use. p-Aminophenyltrimethoxysilane (Gelest) was purified by recrystallization from methanol. Anhydrous methanol (Acros) was... 

Selective silylation. Hexamethyldisilazane alone can effect silylation, but only at elevated temperatures. Rapid silylation of amines, alcohols, and acids can be achieved at 0° in CH2C12 if chlorotrimethylsilane is also present. Selective silylation is also possible by adjustment of the proportions of HMDS and TMSCl. Thus only... 

However, treatment of (2/ ,3/ )-8-rer/-butyl-2,3-dimethyl-l,4-dioxaspiro[5.4]decane with trimethyliodosilane and hexamethyldisilazane in dichloromethane, followed by deprotection of the silyl ethers with tetrabutylammonium fluoride gives, in a combined yield of 78%, diastereomeric (S)-l-[(l) ,2/i)-2-hydroxy-l-methyl-propoxy]-4-tm-butyl-l-cyclohexene and () )-methylpropoxyl]-4- CT7-butyl-l-cyclohexene in a ratio of 20 1 (by GC)83a. 

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

Some researchers have tried to stabilize the MCM wall by a complete hydrofobization of the surface, replacing every silanol group with a trimethy Isi ly 1 group, using e.g. trimethylchlorosilane of hexamethyldisilazane [9], Although this treatment is very effective in se, it yields a surface that is completely unreactive towards subsequent grafting of transition metals. We therefore present a silylation procedure with dimethyldichlorosilane (DMDCS), which allows - upon hydrolysis - a recreation of surface silanols. 

To a solution of diacetone glucose 11 (0.4 g, 1.5 mmol) in 5 mL of pyridine were successively added 1 mL of hexamethyldisilazane and a 0.5 mL of chlorotrimethylsilane. The solution was stirred for 30 min at room temperature and evaporated to dryness. To a solution of the crude silylated ether in CH2C12 (10 mL) were added 2.5 mL of Bu4NF (1M in THF) and A iV -sulfuryldiimidazole (0.46 g, 1.5 eq.). The solution was refluxed for 4 h, diluted with CH2C12, washed twice with water, dried (Na SC ), and evaporated. Flash chromatography of the residue (ether-petroleum ether, 2 1) gave the imidazylate 12 (0.55 g, 91%) mp 98.5°-99.5°C (ether-hexane). 

The quantitative analysis was performed with the technique of gas chromato-graphy/mass spectroscopy. A radioactive sample of Cisobitan , which was labelled with 14C at the geminal methyl groups and which was hexadeuterated in the 4,4-dimethyl-siloxy position, was used for this investigation. Silylation of the metabolic products was carried out with hexamethyldisilazane. 

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