Diethyl sulfate, reaction with

Passing a stream of nitrogen at 95—100°C through a reaction mixture of ethyl ether and 30 wt % oleum prepared at 15°C results in the entrainment of diethyl sulfate. Continuous operation provides a >50% yield (96). The most economical process for the manufacture of diethyl sulfate starts with ethylene and 96 wt % sulfuric acid heated at 60°C. The resulting mixture of 43 wt % diethyl sulfate, 45 wt % ethyl hydrogen sulfate, and 12 wt % sulfuric acid is heated with anhydrous sodium sulfate under vacuum, and diethyl sulfate is obtained in 86% yield the commercial product is >99% pure (97). 

Synonyms 2-Propenoic acid, 2-methyl-2-(dimethylamino) ethyl ester, polymer and 1-ethenyl-2-pyrrolidinone, compd. with diethyl sulfate Quaternium-23 Vinylpyrrolidone/dimethylaminoethyl methacrylate copolymer/diethyl sulfate reaction product... 

In a similar way was prepared HCSCCH2OC2H5, n 1.4039, yield 74-78%. During the addition of diethyl Sulfate the temperature of the mixture was kept between 60 and 70°C. After 2 h of refluxing, the product was distilled off from the reaction mixture through a 20-cm Vigreux column. The distillate was washed with aqueous NHi,Cl. A small part was redistilled b.p. 80°C/750 mmHg. 

These reactions iavolve mostly dimethyl and diethyl sulfate. CycHc sulfates are also reactive, and several have been compared by determining reaction rates with a substituted pyridine or with water (40). In both cases, 1,2-ethylene sulfate is more reactive than 1,3-propylene sulfate or dimethyl or diethyl sulfates. 

Diethyl sulfate can be prepared by a vahety of methods. When ethyl hydrogen sulfate is heated with sodium chloride to 80°C, hydrogen chloride is hberated. The resulting reaction mixture is then distilled at 1.33—2.00 kPa (10—15 mm Hg) at a maximum ketde temperature of 190°C to give diethyl sulfate in 90% yield (95). 

O- Alkylation is comparable to A/-alkylation, but since the sodium salts are water-soluble it is most convenient to treat the phenol or naphthol in aqueous caustic solution with dimethyl sulfate or diethyl sulfate. These are comparatively expensive reagents, and therefore, alkoxy groups are introduced at a prior stage by a nucleophilic displacement reaction whenever possible. 

Diethyl ether is the principal by-product of the reaction of ethyl alcohol with diethyl sulfate. Various methods have been proposed to diminish its formation (70—72), including separation of diethyl sulfate from the reaction product. Diethyl sulfate not only causes an increase in ether formation but is also more difficult to hydroly2e to alcohol than is ethyl hydrogen sulfate. The equiUbrium constant for the hydrolysis of ethyl hydrogen sulfate is independent of temperature, and the reaction rate is proportional to the hydrogen ion concentration (73—75). 

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. 

Preparation of diethyl sulfate by the reaction of ethylene with S02 + H20 using an Ag2S04 catalyst. Other catalytic methods are also described [38]. 

Ferrocenylacetonitrile, 40, 4S Ferrous sulfate, oxidation ferf-butyl alcohol to a,a,a, a -tetramethyl tetra-methylene glycol by hydrogen peroxide and, 40, 90 Fluoboric acid as catalyst for diazomethane etherifications, 41, 9,10 Formaldehyde, reaction with diethyl malonate to form diethyl bis-(hydroxymethyl)malonate, 40, 27... 

A. 3,6-Dibromo-9-ethylcarbazole. In an oven dried, 1-L, round-bottomed flask equipped with a magnetic stir bar and a rubber septum are placed 3,6-dibromocarbazole (10.0 g, 31.0 mmol) (Note 1) and sodium hydroxide pellets (1.2 g, 30.0 mmol) in 500 mL of dry acetone (Note 2) under an argon atmosphere. Diethyl sulfate (4.1 mL, 31.0 mmol) (Note 3) is added dropwise over 15 min to the stirred reaction mixture at room temperature. After the addition, the reaction is stirred for 8 hr at which time all solids are removed by filtration and the solvent is removed under reduced pressure to give a yellow solid. The residue is dissolved in ethyl acetate (200 mL) and successively washed with aqueous saturated sodium bicarbonate (3 x 75... 

SYNTHESIS To a solution of 14.0 g 4-ethoxy-3-methoxyphenol (see the recipe for MME for the preparation of this starting material) in an equal volume of EtOH, there was added a solution of 5.3 g KOH in 100 mL hot MeOH. This was followed with 9.1 g ethyl bromide, and the mixture was held at reflux for 2 h. The first deposition of KBr was apparent in 5 min, and there was rather severe bumping by the end of the reaction. The mixture was diluted with 3 volumes H20 and 1 volume 5% NaOH, and extracted with 2x200 mL Et20. The extracts were pooled, and the solvent removed under vacuum, yielding 14.3 g of a pale amber oil that set to crystals of 2,5-diethoxyanisole with a mp of 44-45 °C. The compound had been reported in the literature from the action of diethyl sulfate on methoxyhydroquinone. 

Substituted imidazole 1-oxides 263 upon treatment with dimethyl or diethyl sulfate furnish l-alkoxy-3-subtituted imidazolium salts 283 that were converted to the tetrafluoroborate 283 (A- = BF4 ) or hexafluorophos-phates 283 (A = PF6-) by treatment with sodium tetrafluoroborate or hexa-fluorophosphate (2007ZN(A)295). The tetrafluoroborates 283 (A = BF4 ) reacted with cyanide ion to give 2-cyanoimidazoles 285 (1975JCS(P1)275). The reaction probably follows a mechanism similar to that suggested to be operative in the pyrazole series encompassing O-alkylation succeeded by nucleophilic addition and elimination of methanol (Scheme 85). 

After cooling the reaction mixture in an ice-bath, the inorganic salts were removed by filtration and washed with acetone. The combined filtrates were concentrated in vacuo. The residual syrup was diluted with saturated brine and extracted with three portions of diethyl ether. The gathered extracts were dried over anhydrous magnesium sulfate, clarified with charcoal and treated with ethereal hydrogen chloride until precipitation was complete. The solid was slurried in diethyl ether and decanted several times, filtered and air-dried to give 3.8 g (86%) of tan 4-(2-di-n-propylaminoethyl)-7-(l-phenyl-lH-tetrazol-5-yloxy)-2(3H)-indolone hydrochloride. Recrystallization from 200 cc of hot acetonitrile gave 2.6 g (59%) of microcrystalline product, m.p. 245°C. 

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