Imidazole silylations

Silyl derivatives have received much attention, they can be utilized to block diverse polar groups (OH, COOH, SH, NH2, =NH). The amino group is not very reactive in silylation reactions. Silyl derivatives are either trimethyl chlorosilanes (TMS), hexamethyldisilazane (HMDS) in conjunction with TMS, silylamines such as trhnethylsilyl diethylamine and trimethylsilyl imidazole, silyl amides such as A,(9-bistrimethylsilylfluoroacetamide (BSTTFA). Example is given by sterols. Isomers with a hydroxy group in the a position are not separated from the (S isomers but when the OH group is converted into a suitable derivative (e.g., TMS) both isomers are well resolved. 

Et3SiCl, Pyr. Triethylsilyl chloride is by far the most common reagent for the introduction of the TES group. Silylation also occurs with imidazole and DMF arid with dimethylaminopyridine as a catalyst. Phenols, carboxylic acids, and amines have also been silylated with TESCl. 

TBDMSCl, imidazole, DMF, 25°, 10 h, high yields. This is the most common method for the introduction of the TBDMS group on alcohols with low steric demand. The method works best when the reactions are mn in very concentrated solutions. This combination of reagents also silylates phenols, hydroperoxides, and hydroxyl amines. Thiols, amines, and carboxylic acids are not effectively silylated under these conditions. ... 

A mixture of 40 mmol or the a-nitro alcohol 1, 48 mmol of (terf-butyldimethyl)chlorosilane or chlorotri-mcthylsilanc, 6.8 g (100 mmol) of I /(-imidazole and 10 mL of DMF is stirred at 20 C for 12 h. Water is added and the mixtnre is extracted with hexane. The combined extract is washed wilh water and sat. aq NaCl and dried over MgS04. Exaporation gives the O-silyl nitro alcohol as an oil which is distilled (bulb-to-bulb) yield 45 - 97%. If unreacled starting material is present in the distillate, it can be removed by chromatography over silica gel (30 g/ l g of product) with l,t,0/pcntanc 1 9 as eluant. 

N-silylated imines 509 react with the Li salts of tosylmethylisonitriles to give 4,5-disubstituted imidazoles in moderate yields [93]. Acetylation of N-trimethylsilyl imines 509 with acetyl chloride and triethylamine affords 72-80% of the aza-dienes 510 these undergo readily Diels-Alder reactions, e.g. with maleic anhydride at 24 °C to give 511 [94] or with dimethyl acetylenedicarboxylate to give dimethyl pyridine-3,4-dicarboxylates [94] (Scheme 5.29). 

Because silylation with HMDS 2/TCS 14 in acetonitrile at ambient temperature converts the unreactive a-chloroketone moiety of 743 into an /Z-mixture of reactive alkyl 4-chloro-3-trimethylsilyloxycrotonates 746a, b [230, 231] which can be isolated and distilled, if humidity is excluded, silylation of 743a, b in the presence of ami dine salts such as 745 gives the desired ethyl or methyl imidazole(4,5)-acetates 748a, b via IMz and 747b. The reaction of formamidine acetate with 746a,b affords 745 (with R=H) in up to 70% yield [232, 233] (Scheme 5.79). As side reactions one must, e.g., take into account the reaction of 746 with ammonia to give 755 which subsequently dimerizes to the pyrazine 756, as discussed in Section 5.5.3. 

Whereas condensation of a-hydroxy ketones such as benzoin and acetoin on heating with formamide [240] or ureas in acetic acid [239, 242] to form imidazoles such as 769 or 770 is a well known reaction, only two publications have yet discussed the amination of silylated enediols, prepared by Riihlmann-acyloin condensation of diesters [241], by sodium, in toluene, in the presence of TCS 14 [241, 242]. Thus the silylated acyloins 771 and higher homologues, derived from Riihl-... 

The O-silylated acyloins such as 1920 c and 1927 are useful synthons for preparation of five-membered aromatic heterocycles such as the substituted imidazole 1925, pyrrole 1926, and furan 1928 [119] (Scheme 12.35). 

The 0-silylation reaction of alcohols is important as a protection method of hydroxyl groups. 0-Silylations of liquid or crystalline alcohols with liquid or crystalline silyl chlorides were found to be possible in the solid state. For example, when a mixture of powdered L-menthol (26), ferf-butyldimethylsilyl chloride (27), and imidazole (28) was kept at 60 °C for 5 h, 0-tert-butyldi-methylsilyl L-menthol (29) was obtained in 97% yield [8] (Scheme 4). Similar treatments of 26 with the liquid silyl chlorides, trimethyl- (30a) and triethylsilyl chloride (30b), gave the corresponding 0-silylation products 31a (89%) and 31b (89%), respectively, in the yields indicated [8] (Scheme 4). However, 0-silylation of triisopropyl- (30c) and triphenylsilyl chloride (30d) proceeded with difficultly even at 120 °C and gave 31c (57%) and 31d (70%), respectively, in relatively low yields. Nevertheless, when the solvent-free silylation reactions at 120 °C were carried out using two equivalents of 30c and 30d, 31c (77%) and 31d (99%) were obtained, respectively, in relatively high yields. 

Further examples for the preparation of 4(5)-substituted imidazoles with AT-sulfa-moylimidazoles are given below. In these cases both the sulfamoyl and the silyl groups are used as protecting functions (bisprotection of the imidazole moiety). 163... 

From silylated iV-sulfamoyl-protected imidazoles or pyrazoles, imidazolyl or pyr-azolyl anions can be generated with the strong base CsF (carbodesilylation) and subsequently treated with electrophiles. In this way 5-substituted imidazoles or pyrazoles can be prepared after the deprotection of N(l) [181... 

The hydroxyl group was usually protected, because cyanohydrins have tendency to racemization or even decomposition. Vinyl ethers or acetal and acid catalysts furnish acetals [62]. Trialkylsilyl chlorides and imidazole are used to give silyl ethers [63]. Commonly used protective groups are silyl ether, ester, methoxy isopropyl (MIP) ether, and tetrahydro-pyranyl ether. ( -Protected cyanohydrins are tolerant to a wider range of cyanide/nitrile transformations and are utilized widely in the synthesis of compounds of synthetic relevance in organic chemistry. 

Imidazole werden durch die gangigen Silylierungsreagentien wie z. B. Hexamethyl-disilazan 1-Trimethylsilyl-imidazol 85%)885 886 oder Chlorsilan/Base [l-Dimethyl-( 1,1,2-trimethyl-pro-pyl)-silyl-imidazol (mit Triethylamin als Base 76%)887 1-Trimethylsilyl-imidazol (aus Natrium-imidazolid mit Chlor-trimethyl-silan 95%)]792 in 1-Position silyliert. 

Der Trialkylsilyl-Rest aus Trichloressigsaure-trialkylsilylestern wird mit Kaliumcarbonat unter Phasentransfer-Katalyse ebenfalls auf Imidazole iibertragen. Nach dieser Methode lassen sich z.B. 1-Trimethylsilyl-imidazol (80%) und l-(tert -Butyl-dimethyl-silyl)-imidazol (75%) herstel-len887. 

The lower stability of (phosphino)(silyl)carbene-group 13 (IIIA) element Lewis acid adducts compared to that of the corresponding imidazol-2-ylidene adducts is easily rationalized by considering the inferior ability of phosphorus to stabilize a positive charge in the ot-position. In other words, once complexed, the carbene... 

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