Dimethyl sulfate polar

The diesters are moderately polar and therefore are miscible with most common organic solvents. SolubiHty in water is low-to-insoluble, with dimethyl sulfate having a water solubiHty of 2.8 g/100 mL at 18.0°C (2). 

With proof-of-concept on the direct methylation in hand, the optimization of the methylation with respect to regioselectivity, yield and isolation conditions was initiated to eliminate the use of 1,4-dioxane and LiH (Table 6.3). Under similar reagent/base conditions (Me2S04, LiOt-Bu), better selectivity was observed in nonpolar solvents (entries 2 and 3) than in polar (entry 1) and aprotic solvents (entries 4 and 5). Mel was a better methylation reagent than dimethyl sulfate under otherwise the same reaction conditions (entries 5 and 7). 

For maximum efficiency, methylation should be a single-phase reaction and so those methods employing aqueous alkali are most suitable for water-soluble compounds and the Purdie method for non-polar compounds. A carbohydrate which is initially soluble in water e.g., starch, dextran) may be less soluble when partially methylated and for this reason an inert solvent e.g., acetone, dioxane, carbon tetrachloride) is often introduced during the later stages of a methylation with dimethyl sulfate. It is interesting to note that methyl a-D-glucopyranoside forms a trithallium derivative which is insoluble in water and consequently the introduction of more than three methoxyl groups by the Menzies method... 

Ternary and secondary alcohols are less acidic than primary alcohols. Methylation of HOCCfCH OH with Me2S04 and alkali hydroxide in aqueous medium, analogous to die procedure for HG=CCH20CH3 (exp. 2.1), is therefore expected to give a poor result. In the aprotic DMSO, however, the concentration of the alkoxide HC=CC(CH3>20K will be sufficient, while the alkylation will proceed smoothly in this strongly polar solvent. Undoubtedly, pan of the dimethyl sulfate will react with KOH to give methanol (which may further react to dimethyl ether). Therefore, an excess of Me2S04 and KOH is used. 

Hydroxybenzo[6]thiophenes exist as oxo tautomers and are referred to as thiooxindoles. O- Alkylation of thiooxindole is favoured in polar aprotic solvents thus NaH/HMPT/Me2S04 gives a 90% yield of 2-methoxybenzo[6]thiophene. Treatment of thiooxindole with two equivalents of NaOH and dimethyl sulfate, or... 

The O-alkylation of carboxylates is a useful alternative to the acid-catalyzed esterification of carboxylic acids with alcohols. Carboxylates are weak, hard nucleophiles which are alkylated quickly by carbocations and by highly reactive, carbocation-like electrophiles (e.g. trityl or some benzhydryl halides). Suitable procedures include treatment of carboxylic acids with alcohols under the conditions of the Mitsunobu reaction [122], or with diazoalkanes. With soft electrophiles, such as alkyl iodides, alkylation of carboxylic acid salts proceeds more slowly, but in polar aprotic solvents, such as DMF, or with non-coordinating cations acceptable rates can still be achieved. Alkylating agents with a high tendency to O-alkylate carboxylates include a-halo ketones [42], dimethyl sulfate [100,123], and benzyl halides (Scheme 6.31). 

There are numerous examples of quaternizing alkylations of imidazoles using such diverse reagents as alkyl, alkenyl or aralkyl halides, ethyl chloroacetate, phenacyl bromide or dimethyl sulfate. Since water is frequently held very tenaciously by imidazole quaternary salts the compounds are often best prepared in anhydrous conditions (e.g. dry benzene solvent in a dry nitrogen atmosphere) even though the reaction is commonly slower in non-polar solvents. 

Phosgene reacts with a high temperature ionic liquid, LiF-NaF-KF, at 550 C to give a mixture of COF (70%), CO (25%), SiF (4-5%) and traces of COCIF and unreacted COClj [1978, 1979]. However, under far milder conditions, phosgene will react with anhydrous sodium fluoride in a polar solvent (t >20, e.g. ethanenitrile, nitromethane, dimethyl sulfate, ethylene carbonate or tetrahydrothiophene-1,1-dioxide) at 30 "C to give high yields (ca. 80%) of pure COF [631] ... 

To a 200-mL round-bottom flask equipped with a stirring bar and an addition funnel was added 5 g (17.7 mmol) of the diketone prepared above dissolved in 60 mL of acetone and 12 mL of dimethyl sulfate (DMS). The mixture was stirred while a solution of 20% KOH in methanol was added at the rate of 1-2 drops/10 s. TLC indicated that as the starting material was being consumed, both a more polar intermediate and a less polar product began to appear. After the addition of an additional 10 mL DMS, the reaction mixture was poured into ether and washed with water (2 X). The organic extracts were concentrated and residual DMS was removed under high vacuum. The dark oily residue that remained was chromatographed on sihca gel (flash column... 

Another environmentally friendly substance that is a promising candidate as a reagent or solvent is dimethyl carbonate, which has polar character and a relatively low boiling point (90°C). It could replace less environmentally friendly substances such as dimethyl sulfate and methyl halides as a reagent that supplies the methyl (CH3) group in reactions ... 

Similar results have been reported using a phase transfer catalyzed alkylation where dimethyl sulfate functioned as electrophile [4]. In this case, the reaction rate was sensitive to changes in the stirring rate suggesting that the reaction may be non-catal-ytic and occurring in the polar solvent (dimethyl sulfate). 

They are produced by alkylation (quatemarization) of tertiary amines with methylchloride, dimethyl-sulfate and ethylene oxide at 50-100 °C in a polar solvent, such as ethanol, within several hours or much faster under pressure with an excess of the alkylating agent. 

In a recently published paper6, on the investigation of AN copolymerization with the quartemary salt of l,2-dimethyl-5-vinylpyridinium sulfate (DMVPS) in dimethyl sulfoxide (DMSO) with 2,2 -azoisobutyronitrile as initiator, and in aqueous medium in the presence of the potassium persulfate/sodium metabisulfite oxidation-reduction system at 60 °C, the authors found the reactivity of the monomers, especially that of MVPS (methylvinylpyridin sulfate) to depend significantly on the polarity of the medium. 

The sodium and potassium salts of glutaconaldehyde are soluble only in polar solvents such as water, dimethyl sulfoxide, N,N-dimethylformamide, pyridine, and methanol. However, the stable tetrabutylammonium salt is soluble in relatively nonpolar solvents such as chloroform and ethyl acetate. It may be prepared from the potassium salt in the following manner. In a 1-1. Erlenmeyer flask equipped with a magnetic stirring bar are placed a solution of 13.6g. (0.1 mole) of crude glutaconaldehyde potassium salt in 200 ml. of water and a solution of 33.9 g. (0.1 mole) of tetrabutyl-ammonium hydrogen sulfate in 200 ml. of ice-cold water, the pH of wliich was adjusted to 10 by adding aqueous 2M sodium hydroxide. 

After selective generation of the syn- or anH -enolate of an amide, it is usually reacted with a haloalkane, often the iodide. Allylic and benzylic bromides also react satisfactorily, and dimethyl and diethyl sulfate have also been used in some cases. A solution of the alkylating agent in an ethereal solvent, usually tetrahydrofuran, is added to the enolate, usually at low temperature. A polar, aprotic cosolvent, such as hexamethylphosphoric triamide, is frequently used as an additive in the alkylation step. The use of this suspected carcinogen is prohibited in some countries, which limits the usefulness of many of the reactions described below. However, similarly effective in many cases are some ureas, such as the commercially available 1,3-dimethyl-3,4,5,6-tetrahydro-2(l//)-pyrimidinone (DMPU)12. 

---