MEERWEIN Alkylation reagent

MEERWEIN Alkylation reagent 250 MEERWEIN PONNDORF - VERLEY Reduction 251... 

MEERWEIN Alkylating Reagent R30 BF4 reagent for O-alkylation of amides (see 1st edition). 

MEERWEIN Alkylation reagent R3CPBF4 reagent tor O-aikylaton of amides... 

N-Alkylations, especially of oxo-di- and tetra-hydro derivatives, e.g. (28)->(29), have been carried out readily using a variety of reagents such as (usual) alkyl halide/alkali, alkyl sulfate/alkali, alkyl halide, tosylate or sulfate/NaH, trialkyloxonium fluoroborate and other Meerwein-type reagents, alcohols/DCCI, diazoalkanes, alkyl carbonates, oxalates or malon-ates, oxosulfonium ylides, DMF dimethyl acetal, and triethyl orthoformate/AcjO. Also used have been alkyl halide/lithium diisopropylamide and in one case benzyl chloride on the thallium derivative. In neutral conditions 8-alkylation is observed and preparation of some 8-nucleosides has also been reported (78JOC828, 77JOC997, 72JOC3975, 72JOC3980). 

Meerwein s reagent, triethvloxonium tetrafluoroborate, is a powerful ethylating agent that converts alcohols into ethyl ethers at neutral pH. Show the reaction of Meerwein s Teagent with cyclohexanol, and account for the fact that trialkyloxonium salts are much more reactive alkylating agents than alkyl iodides. 

Alkylation of 1//-azepin-2(3//)-ones, e.g. 17. with Meerwein s reagent provides ready access to 2-ethoxy-3//-azepines.72,81,228... 

It is very interesting, however, that in alkane potassium diazoate alkylations with Meerwein s reagent (triethyloxonium tetrafluoroborate, Et30+BF4) in CH2C12 suspensions or with alkyl halides in hexamethylphosphoric triamide solutions, azoxy compounds (6.4) are formed, i.e., alkylation takes place at the (3-nitrogen (Moss et al., 1972). 

There are several examples of alkyl halides reacting with 1,2,3-thiadiazoles at nitrogen to yield either salts or mesoionic compounds <1996CHEC-II(4)289>. Similarly, with Meerwein s reagent, several substituted thiadiazoles yielded various 2- and 3-methylated 1,2,3-thiadiazoles (Scheme 4 Table 8) <1993JHC301>. The isomer ratios were determined by integrating the methyl singlets in the H NMR spectra and the compounds were further studied by 1SN NMR spectroscopy (Section 5.07.3.4). 

After (presumed). S-alkylation of diphenyl sulfide with Meerwein s reagent, heating the resultant material at 175°C gave a small quantity of thianthrene as a component of a complex product mixture (71JOC1513). 

Valine-derived (5)-2-ethoxy-4,5-dihydro-4-isopropyloxazole, obtained by alkylation of 4-isopropyl-2-oxazolidinone with Meerwein s reagent, has been used to convert secondary tion and alkylation occurs smoothly to give alkylated derivatives I, which can be deprotected to give tetrahydroisoquinolines 2 with recovery of the chiral auxiliary28. 

Piperazine-2,5-diones, in which both amino acid units are primary, lead to bislactim ethers on O-alkylation with Meerwein s reagents. No selectivity in this reaction has been demonstrated so far. Such bislactim ethers (171) have been prepared and extensively used by Schollkopf and his school [79AG(E)863, and later papers]. During the preparation of these bislactim ethers, neutralization of the initially formed bis-tetrafluoroborate salt is carried out with phosphate buffer to avoid racemization. 

O -Alkylations of azepin-2-ones, and benzazepin-2-ones, are most efficiently brought about by trialkyloxonium tetrafluoroborates (Meerwein s reagents) (B-69MI51600,73JOC1090, 81HCA373). S-Alkylation of the thiones is effected similarly. These oxonium salts have also proved useful for the alkylation of azepinedione precursors of azatropones and azatropolones (72JOC208) (see also Section 5.16.3.1.2). 5//-Dibenz[f>,e]azepine-6,11 -dione with triethyloxonium tetrafluoroborate O-ethylates at the amide carbonyl and not at the ketonic carbonyl as was first proposed (72AJC2421). 

In some procedures, thioacetal cleavage occurs after alkylation at the sulfur atom with a reactive alkylating reagent such as methyl iodide, tnalkyloxonium tetrafluoroborate (Meerwein salt), or ethyl trifluoromethanesulfonate to give a tnalkylsulfonium salt. 

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