Sulfuric acid reaction with diethyl sulfate

The more complex the olefin, the lower the temperature and pressure at which reaction (1) will take place. Furthermore, ethylene requires a more concentrated sulfuric acid for efficient absorption than its homologues. Both mopo- and dialkyl sulfates are formed simultaneously when ethylene or propylene is absorbed in sulfuric acid., An appreciable amount of diethyl sulfate is formed when the acid has reacted with about inole of ethylene. In addition, appreciable amounts of the corresponding ethers are produced. Ethyl ether, for example, is formed to a considerable extent by the reaction of alcohol with diethyl sulfate. Polymer formation, particularly for higher olefins, is also an undesirable side reaction. 

ILLUSTRATION 5.1 Determination of the Rate Law for Reaction of Sulfuric Acid with Diethyl Sulfate... 

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). 

In the final production preparation, a mixture of ethyl methyl(3-benzoylphenyl)cyano-acetate (48 g), concentrated sulfuric acid (125 cc) and water (125 cc) is heated under reflux under nitrogen for 4 hours, and water (180 cc) is then added. The reaction mixture is extracted with diethyl ether (300 cc) and the ethereal solution is extracted with N sodium hydroxide (300 cc). The alkaline solution is treated with decolorizing charcoal (2 g) and then acidified with concentrated hydrochloric acid (40 cc). An oil separates out, which is extracted with methylene chloride (450 cc), washed with water (100 cc) and dried over anhydrous sodium sulfate. The product is concentrated to dryness under reduced pressure (20 mm Hg) to give a brown oil (33.8 g). 

To the crude diethyl o-nitrobenzoylmalonate is added a solution of 60 ml. of glacial acetic acid, 7.6 ml. of concentrated sulfuric acid, and 40 ml. of water, and the mixture is heated under reflux for 4 hours (Note 4) or until no more carbon dioxide is evolved. The reaction mixture is chilled in an ice bath, made alkaline with 20% sodium hydroxide solution, and extracted with several portions of ether. The combined ethereal extracts are washed with water and dried with anhydrous sodium sulfate followed by Drierite, and the solvent is removed by distillation. On fractional distillation of the residue, 27.0-27.4 g. (82-83%) of light-yellow o-nitroacetophenone boiling at 158-159°/16 mm. is obtained n 1.548, wg 1.551, df 1.236) (Note 5). 

A 1-M hexane solution of di isobutyl aluminum hydride (400 mL, 0.40 mol) (Note 10) is added dropwise with stirring at 0°C oxer a 1-hr period. The solution is stirred for 2 additional hr at 0°C. To quench the reaction 200 mL of methanol is carefully added to the stirred reaction mixture, followed slowly at first then more rapidly with 400 mL of water and then 300 mL of 10 sulfuric acidt solution. After the mixture is stirred for 10 min, it is transferred to a separatory funnel and 500 mL of 10% sulfuric acid solution is added. The separatory funnel is shaken vigorously for 5 min and the organic phase 1s separated. The aqueous phase is extracted four times with 300 mL of diethyl ether. The organic phases are combined and washed twice with 300 mL of saturated sodium bicarbonate solution, twice with 300 mL of water, twice with 300 mL of brine, and dried over magnesium sulfate. Solvent removal on a rotary evaporator followed by short path distillation at reduced pressure affords 31-34 g (40-44%, based on 3-ethoxy-6-methyl-2-cyclohexen-l-one) of 4-(E-l,2-dichlorovinyl )-4-methy 1-2-cyclohexen-l-one (1) as a colorless oil, bp 75-78°C (0.1 mm) (Note 11). 

A mixt of 5g of 1 -methyl-5-aminotetrazole from above, 17ml of 96% sulfuric acid, and 300ml of w is added dropwise over 1 hr to a soln of 53g of Na nitrite in 500ml of w at 45°. The reaction mixt is stirred an additional hr at 45° and then cooled to 25°. The reaction is extracted with three 50-ml portions of methylene chloride. The methylene chloride extract is washed once with 5% Na bicarbonate and once with w. It is then dried over Mg sulfate and evapd, leaving 1.5g of yellow oil. This is combined with 6.0g of oil from another reaction, so as to have enough material for the next step, and dissolved in a minimum vol of diethyl ether. The ether soln is passed thru a neutral alumina column. The product from the column is then recrystd twice from ether to yield 3.5g of l-methyl-5-nitrotetrazole. This compd is so light sensitive that it must be stored in methylene chloride soln at 0° in the dark... 

To 1.13 g of (-)-7,8-difluoro-2,3-dihydro-3-methyl-4H-[l,4]benzoxazine was added 1.58 g of diethyl ethoxymethylenemalonate, and the mixture was stirred at 130-140°C for 70 min. The reaction mixture was subjected to column chromatography using 50 g of silica gel and eluted with chloroform to obtain 2.47 g of diethyl [(-)-7,8-difluoro-3-methyl-2,3-dihydro-4H-[l,4] benzoxazin-4-yl]methylenemalonate. This product was dissolved in 5 ml of acetic anhydride, and 10 ml of a mixture of acetic anhydride and concentrated sulfuric acid (2/1 by volume) with stirring under ice-cooling, followed by stirring at 50-60°C for 40 min. To the reaction mixture were added ice and an aqueous solution of sodium bicarbonate, and the product was extracted three times with 150 ml portions of chloroform. The combined extract was washed with water, dried over anhydrous sodium sulfate and concentrated. The precipitate was washed with a small amount of diethyl ether to yield 1.32 g of (-)-ethyl 9,10-difluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido[l,2,3-de][l,4] benzoxazine-6-carboxylate. 

A solution of 12.5 g. (0.54 gram atom) of sodium in 125 g. of absolute ethanol (p. 142) is cooled and stirred while a mixture of 36 g. (0.50 mole) of methyl ethyl ketone and 73 g. (0.50 mole) of diethyl oxalate is added slowly. The reaction mixture is allowed to stand for 17 hours, after which it is cooled and acidified with dilute sulfuric acid. The mixture is extracted with ether the ether extracts are dried over sodium sulfate and distilled. All distillate boiling up to 100°/11 mm. is collected, and then the fraction boiling at 70-80°/0.6 mm. is collected separately. Redistillation of the latter fraction gives 50 g. of ester boiling at 75-78°/0.6 mm. 

The reaction mixture was allowed to warm gradually to 50°C. The reaction was quenched by pouring into ice water. The aqueous suspension was heated to hydrolyze p-chlorobenzenesulfonyl chloride (II) to the water-soluble sulfonic acid. The desired product was filtered and washed with water until essentially neutral. Bis (4-chlorophenyl) sulfone was purified by recrystallization from benzene—m.p. 145°-147°C (4). Extremely low yields were obtained by this process. By contrast, yields in excess of 90% have been reported in processes that involve the reaction of chlorobenzene with sulfur trioxide and dimethyl or diethyl sulfate (5, 6). 

---