Trimethylsilyl sodium iodide

Trimethylsilyl iodide [16029-98-4] (TMSI) is an effective reagent for cleaving esters and ethers. The reaction of hexamethyldisilane [1450-14-2] with iodine gives quantitative conversion to TMSI. A simple mixture of trimethylchlorosilane and sodium iodide can be used in a similar way to cleave esters and ethers (8), giving silylated acids or alcohols that can be Hberated by reaction with water. 

Trimethylsilyl iodide can be substituted for the trimethylsilyl triflate catalyst in the reactions of aliphatic aldehydes. TMSI can be generated conveniently in situ either from trimethylsilyl chloride and sodium iodide in acetonitrile314 or from hexamethyldisilane and iodine in dichloromethane334 or pentane.338 It is noted that neither triisopropylsilane nor PMHS is an effective reducing agent for this purpose when used with TMSI under these conditions.314,334... 

Another variation of this method involves the treatment of an acetonitrile solution of the aryl aldehyde, trimethylsilyl chloride, and either sodium iodide, if iodide products are desired, or lithium bromide, if bromide products are desired, with TMDO. After an appropriate reaction time (5-195 minutes) at a temperature in the range of —70° to 80°, the upper siloxane layer is removed and the benzyl iodide or bromide product is isolated from the remaining lower portion after precipitation of the inorganic salts by addition of dichloromethane. For example, p-anisaldehyde reacts to form /i-rnethoxybenzyl bromide in 84% isolated yield under these conditions (Eq. 200).314,356... 

Di-w -pentyl Ether [TMSI-Catalyzed Reduction of an Aldehyde to a Symmetrical Ether].314 A mixture of sodium iodide (0.15 g, 1 mmol), 1-pentanal (1.06 mL, 10 mmol), and trimethylsilyl chloride (2.0 mL, 15.4 mmol) was stirred in MeCN (5.0 mL) at room temperature for 10 minutes, after which 1,1,3,3-tetramethyldisiloxane (TMDO, 1.79 mL, 10 mmol) was added. When the exothermic reaction had ended (30 minutes), a solution of 2.5 N HF in MeOH (30 mL) was added to the reaction mixture, which was then refluxed for 5 minutes. Work-up was carried out by diluting the solution with CH2CI2 (40 mL), washing with water (30 mL) and saturated aqueous NaHC03 solution (20 mL), drying, and evaporating the solvents. Crude di-n-pentyl ether was purified by distillation 0.65 g (84%) bp 185-1897760 Torr. 

When the enone 182 was heated with trimethylsilyl chloride (TMSC) and sodium iodide in acetonitrile, a mixture of the 3,1-benzoxazines 183 and 184 in a ratio of 1 5 was formed stereospecifically. The a,/3-unsaturated ketones in TMSC/Nal first gave jS-iodoketones thereafter a tertiary carbo-cation was formed, and subsequent acetonitrile addition resulted in the oxazines 183 and 184 (89TL4741). 

Chloramine-T-Sodium iodide, 70 Iodine-Trimethylsilyl chlorochromate, 327... 

DIENES Alkylaluminum halides. 1,4-BistrimethylsiIyl-2-butyne. Chlorotnmethylsilan e-Sodium iodide. Dicyclopentadienyl( 1 triniethylsilylallyl (titanium. Dimcthylformamide dimethyl acetal. Sodium dicarbonylcyclopentadienyl ferrate. Titanium(O). Tri-/i-hutyl(iodomcthyl)tin. Trimethylsilyl-allyllitimim... 

Triethylamine Trimethylsilyl chloride Sodium iodide Palladium on carbon L-Cinchonidine Benzyl bromoacetate (trans)-4-Cyclohexyl-L-proline, hydrochloride... 

An interesting example of an application of this method pertains to the synthesis of pharmacologically active synthetic A1 -tetrahydrocannabinoids 134) of the type 267 which have a lipophilic tertiary alkyl side-chain. Equation 84 shows that organo-titanium chemistry provides a versatile means to prepare the precursors 264 (65-80 %)133). Demethylation of 264 using trimethylsilyl chloride and sodium iodide affords the resorcinol derivatives 265 ( 95%)133>. Compounds of this type have been previously condensed with 266 in the presence of acids to form the A1(6)-isomers of 267, which in turn can be converted into 267135). It should be mentioned that the meta-substitution pattern of 265 prohibits simple Friedel-Crafts alkylation of resorcinol, which is the reason why alternative multistep syntheses of 264 have had to be developed l34 136>. 

Trimethylsilyl iodide converts alcohols to iodides. The disadvantage of this method is the expensive reagent, which is avoided if trimethylsilyl chloride and sodium iodide are used instead (equation 27). Trimethylsilyl polyphosphate (PPSE), which is prepared from hexamethyldisiloxane and phosphorus pentoxide, also activates alcoholic hydroxy groups for substitutions with iodide anions (equation 28). ... 

The preparation can be performed at ambient temperature by use of trimethylsih I iodide prepared in situ from trimethylsilyl chloride and sodium iodide [68]. 

A solution of l,5-bis(4-methoxyphenyl)pentane (14.3 g, 50 mmol), trimethylsilyl chloride (10.8 g, 0.1 mol), sodium iodide (15 g, 0.1 mol) in 40 mL of acetonitrile was refluxed for 12 The mixture was cooled and taken up in benzene and water. The organic layer was washed with brine and the solvent was evaporated to give 12.7 g of crude 1,5-bis-(4-hydroxyphenyl)pentane. 

A new synthesis of 2,4,4,6-tetramethyl-4//-l,3-oxazine (155) simply involves a reductive cycloaddition of 4-methylpent-3-en-2-one and acetonitrile in the presence of trimethylsilyl chloride and sodium iodide (Scheme 42) <89TL4741>. Other cycloaddition reactions have been used previously to synthesize 4//-l,3-oxazines and this methodology has been extended to include cycloadditions between alkynes and l-oxa-3-azabuta-1,3-dienes. For example, phenylethyne and the A-benz-oylimine (156) afford 4,4-bis(trifluoromethyl)-2,6-diphenyl-4//-l,3-oxazine (157). The reaction proceeds through a Michael-type addition between the alkyne and the heterodiene giving an adduct which when heated to 80-90°C cyclizes to the oxazine (Scheme 43) <83CC945,89ZN(B)1298>. 

New ways continue to be reported of carrying out familiar transformations of pyridine A -oxides. Thus a number of pyridine A -oxides have been deoxy-genated in acetonitrile with trimethylsilyl chloride-sodium iodide and zinc. The method is not so high-yielding when electron-withdrawing substituents are present. " The complexes that are formed by pyridine A -oxides and antimony pentachloride lose hydrogen chloride on heating subsequent hydrolysis yields 2(l//)-pyridones (Scheme 23). ... 

A. Casarini, P. Denbeck, G. Reginato, A. Ricci, G. Secondi, Tetrahedron Lett. 1991, 32, 2169-2170. In a recent method for the preparation of cyanoalkynes, terminal acetylenes are coupled with cuprous cyanide in the presence of trimethylsilyl chloride water, catalytic amounts of sodium iodide and acetonitrile in DMSO at 50 C F.-T. Luo, R.-T. Wang, Tetrahedron Lett. 1993, 34, 5911-5914. 

Metallated acetylenes, obtained by hydrozirconation, hydroalumination or hydroboration, react with elemental iodine to give ( )-iodoalkene. Terminal alkynes 229 (R = octyl or decyl) add hydrogen iodide, generated from the boron triiodide/A,A-diethylaniline complex and acetic acid, in a Markovnikov sense to afford the iodoalkenes 230. cw-Addition of hydrogen iodide, produced in situ from trimethylsilyl chloride and aqueous sodium iodide, to a number of internal alkynes has been reported... 

Additions of methyl 2-bromopalmitate [5d] in the presence of sodium iodide to trimethylsilyl enol ethers [24] yielded methyl 2-alkyl-4-oxoalkanoates [25] (Scheme 11). 

In another report, catalytic transsilylation of trimethylsilyl benzoate with a number of chlorosilanes was disclosed." A, A -dimethylformamide (DMF) and sodium iodide were used as catalysts. Both DMF and sodium iodide were reported to catalyze with almost equal efficiency however, the formation of insoluble sodium chloride and discoloration of solution made sodium iodide a less suitable catalyst. Then 1 mol% of DMF was used in THF as a solvent under reflux conditions for 24 h. The silyl ester was obtained in 77% yield after removal of trimethylsilyl chloride under reduced pressure. (See Scheme 3.5.)... 

One of the more fundamental methods for generation of the o-xylylene intermediate is 1,4-elimination from o-xylene derivatives. o-Xylene di-, tri-, or tetrabromides undergo intramolecular 1,4-dehalogenation by means of sodium iodide [102], lithium [103], zinc [104], copper [105], iron [106], and chromium [107]. Hoffman degradation of (o-methylbenzyl)trimethylammonium hydroxides [108], as well as the more recently developed fluoride ion-induced elimination from [o-[a-(trimethylsilyl)alkyl]benzyl]trimethylammonium halides [109], have also been effectively utilized in the generation of 2. 

New reagents for the primary and secondary alcohol to alkyl iodide conversion, with inversion at secondary centres, are diphosphorus tetraiodide (P2I4), a well characterized and stable solid, and mixtures of triphenylphosphine with iodine and imidazole or with 2,4,5-tri-iodoimidazole. The P2I4 system also iodinates tertiary alcohols. Trimethylsilyl iodide is known to convert alcohols into iodides (2,128), and some more systems that are believed to generate trimethylsilyl iodide in situ have been found to effect the alcohol to iodide conversion (c/. 3,151). Trimethylsilyl chloride-sodium iodide in acetonitrile produces iodides from alcohols direct or from their trimethylsilyl ethers. Hexamethyldisilane-... 

Reactions.—Some examples of new methods for ether cleavage have been dealt with in an earlier section (Protection of Alcohols). Aliphatic and aromatic methyl ethers can be cleaved efficiently by an aluminium halide-ethanethiol combination the process has been rationalized according to the hard and soft acid-base principle. Several methods for the (presumed) in situ preparation of trimethylsilyl iodide, a known reagent for the cleavage of ethers (2,131), have been disclosed recently in an effort to circumvent the expense and moisture sensitivity of MeaSil. (Some of these methods have been mentioned earlier in this Report in connection with the conversion of alcohols into alkyl iodides.) Reports include two on trimethylsilyl chloride-sodium iodide, one on phenylseleno-trimethylsilane-iodine [equation (18)], and three on hexamethyldisilane-iodine [equation (jq)] 102,142,143 method has the advantage of... 

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