Dimethyl ether, protonated alkylation with

Another common solvent that contains the oxygen atom easily available for coordination with metal cations is THE. The ability of anion-radicals to remove a proton from the position 2 of THE is sometimes a problem. Dimethyl ether is more stable as a solvent its oxygen atom is also exposed and can coordinate with a metal cation with no steric hindrance from the framing alkyl groups. An added advantage of dimethyl ether is that, because of its low boiling point (-22°C), it can be readily removed after reductive metallation and replaced by the desired solvent. The use of aromatic anion-radicals in dimethyl ether (instead of THE) is well documented (Cohen et al. 2001, references therein). 

This technique was used to synthesize some cyclohexane derivatives by substitution with electrophiles specifically in the axial or equatorial position. Whereas alkylation with dimethyl sulfate occurred smoothly, alkylation with haloalkanes failed completely. Rather nonstereoselective protonation of the lithium compound, as well as dehydrogenation to enol ethers, occurred. Operation of single electron transfer processes are believed to account for these results27. 

Other proton donors (HBr, HC1, H2S, H2Se, HCN, CH3SH) can have a similar promoting effect as water (56, 61, 70, 71). For alkylation of benzene with propylene the activity of HNaX, CaX, and NaX increased on addition of C3H7C1 (72), and CCU had a similar effect on the activity of NaY, CdY, and BaY (73), but it was not understood why the activity of CaY for the same reaction decreased on addition of the same products. The activity of NaY for alkylation increases considerably by introducing dimethyl ether and n-butyraldehyde. 

The formation of the above anions ("enolate type) depend on equilibria between the carbon compounds, the base, and the solvent. To ensure a substantial concentration of the anionic synthons in solution the pA" of both the conjugated acid of the base and of the solvent must be higher than the pAT -value of the carbon compound. Alkali hydroxides in water (p/T, 16), alkoxides in the corresponding alcohols (pAT, 20), sodium amide in liquid ammonia (pATj 35), dimsyl sodium in dimethyl sulfoxide (pAT, = 35), sodium hydride, lithium amides, or lithium alkyls in ether or hydrocarbon solvents (pAT, > 40) are common combinations used in synthesis. Sometimes the bases (e.g. methoxides, amides, lithium alkyls) react as nucleophiles, in other words they do not abstract a proton, but their anion undergoes addition and substitution reactions with the carbon compound. If such is the case, sterically hindered bases are employed. A few examples are given below (H.O. House, 1972 I. Kuwajima, 1976). 

The reactions in which the methyl ketone loses a primary proton are all fast reactions, and the direction of the reaction is determined by the fact that an electron-releasing alkyl group slows down the removal of the secondary proton from the methylene group. On the other hand a slow reaction, like the base-catalyzed reaction of ketones with dimethyl sulfate in ether, gives a product corresponding to the removal of a proton from the more alkylated carbon.418... 

The red shift of the HCl stretch, listed in the last row of Table 3.28, is considerably larger than in H O HCl. Nonetheless, this shift of 170 cm is only about half of the experimental quantity of 316 cm. The same trends are observed in. solid matrix. When the proton acceptor in the H20---HC1 complex is changed to dimethyl (or diethyl) ether, the red shift of the HCl stretch increases by several hundred cm Similarly increased red shifts vv hen the base is alkylated are noted for HF and HBr as proton donors. The sulfur analogs, namely, H2S, Mc2S, and 128, obey similar patterns when paired with HF, HCl, and HBr". ... 

Reaction of estrone methyl ether with 2,2-dimethylpropane-l, 3-diol in the presence of a catalytic amount of acid leads to derivative 26-1, in which the ketone at 17 is protected as an acetal (Scheme 3.26). Treatment of this intermediate with pyridinium chlorochromate leads to oxidation of the Cg benzylic carbon atom to a carbonyl group (26-2). Potassium tert-butoxide abstracts a proton from the adjacent methylene at C7 alkylation of the resulting anion with 4-(A, A -dimethyl)butyl iodide gives 26-3 as a mixture of diastereomers. The carbonyl group is next reduced to an alcohol by means of sodium borohydride (26-4). Dehydration of the newly introduced hydroxyl group is arguably facilitated by the adjacent aromatic ring (26-5). Aqueous acid removes the 17-acetal to afford 26-6, which is in essence an equilinin derivative. 

Liquid electrolyte lithium-ion technology uses mixtures of aprotic organic solvents (which are not likely to donate a proton) because the graphite-lithium electrode is very unstable in the presence of compounds with labile hydrogen.22 The solvents used are alkyl earbonates (carbonates of ethylene, propylene, dimethyl, etc.) ethers, in which a lithium salt that... 

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