Diethyl sulfate

Diethyl sulfate (DES) is a highly toxic chemical compound with formula (C2H5)2S04. It occurs as a colorless liquid with a peppermint odor. 

Diethyl sulfate is used as an alkylating agent to prepare ethyl derivatives of phenols, amines, and thiols. 

DES is best manufactured by using chlorosulfonic acid as sulfonating agent 2C,H50H +CISO3OH (C2H5)2S04 

It is important that commercial alcohol 95-96% is first distilled in a packed colunrn to 99.5% and passed through a molecular sieve to make the alcohol bone dry. The reacted mass is then distilled under vacuum in glass lined well stirred vessels to produce DES of international grade. 

A modification of the above with lower purity and yield can be achieved with sulfur trioxide being injected in the suction of the circulating pump. 

---

See the same reference in Pihkal for details on how to use ethyl iodide instead of diethyl sulfate. 

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. 

An alkah-stable dye. Direct YeUow 12 (Cl 24895) [2870-32-8] (12), is made by ethylating Direct YeUow 4 (11) with ethyl chloride or diethyl sulfate. 

Table 2. Selected Physical Properties of Dimethyl and Diethyl Sulfate...

Alcohols react readily ia alkaline solution. Conditions for pentaerythhtol are typical (13). Use of alcohoHc KOH ia dimethyl sulfoxide gives fair to good ethyl ether yields with diethyl sulfate at 50—55°C (14). 

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. 

The only commercially important dialkyl sulfates are dimethyl sulfate and diethyl sulfate. Estimated worldwide production in 1996 for dimethyl sulfate was 90,000 metric tons per year. Dimethyl sulfate was initially made by vacuum pyrolysis of methyl hydrogen sulfate ... 

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). 

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). 

Lower dialkyl sulfates were made from the alcohols in earlier work the reaction mass at ca 100°C was stripped by a recirculated inert-gas stream, and the product was recovered by passage through a partial condenser. Yields of 90% for diethyl sulfate and 85% for dimethyl sulfate were reported (98). 

Dimethyl and diethyl sulfate are available in a vahety of containers from 0.5-kg glass botdes to tank cars. Diethyl sulfate is somewhat less toxic than dimethyl sulfate and is considered noncorrosive, but dimethyl sulfate is classified as a corrosive Hquid and ICC regulations must be observed. Mild steel to 306 stainless steel is used for large-volume storage. Dimethyl sulfate is manufactured by E. I. du Pont de Nemours Co., Inc., and diethyl sulfate by Union Carbide Corporation. Other producers are Rhc ne-Poulenc and Hoechst-Celanese. 

The acute toxicities of various sulfates have been reported (126). Generally, dimethyl sulfate (LD q 440 mg/kg in rats) is more toxic than diethyl sulfate (LD q 880—1412 mg/kg in rats), which is more toxic than dibutyl sulfate (lowest observed toxic dose, 9500 mg/kg in rats). Ethylene sulfate is more toxic than dimethyl sulfate (40). 

Diethyl Sulfate, Material Safety Data Sheet, Union Carbide, New York, 1976. 

Tertiary Amine-Containing Copolymers. Copolymers based on DMAEMA (dimethylarninoethyl methacrylate) in either free amine form or quatemized with diethyl sulfate or methyl chloride have achieved commercial significance as fixatives in hair-styling formulations, especially in the weU-pubhcized "mousses" or as hair-conditioning shampoo additives. This success has occurred because the cationic charge affords substantive resins that strongly adhere to the hair (141). 

The most successful of these products contain high ratios of VP to DMAEMA and are partially quatemized with diethyl sulfate (Polyquaternium 11) (142—144). They afford very hard, clear, lustrous, nonflaking films on the hair that are easily removed by shampooing. More recendy, copolymers with methyl vinyl imidazoliiim chloride (Polyquaternium 16) (145) or MAPTAC (methacrylamidopropyltrimethyl ammonium chloride) (Polyquaternium 28) have been introduced. Replacement of the ester group in DMAEMA with an amide analog as in Polyquaternium 28 results in a resin resistant to alkaline hydrolysis and hence greater utility in alkaline permanent-wave and bleach formulations (see Quaternary ammonium compounds). 

From Diethyl Sulfate. Several processes (32—34) have been proposed for manufacture of ethyl chloride based on the following reaction ... 

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. 

Absorption of ethylene in concentrated sulfuric acid to form monoethyl sulfate (ethyl hydrogen sulfate) and diethyl sulfate ... 

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). 

A more recent concept (341) is that ether is principally derived from the reaction between diethyl sulfate and ethanol. 

Alkylations of cinnolin-4(lf/)-one (8) with methyl iodide, ethyl iodide, dimethyl and diethyl sulfates, isopropyl bromide, benzyl chloride, etc. take place predominantly at position 2 to give 2-alkyl-4-hydroxycinnolinium anhydro salts (83), together with small amounts of l-methylcinnolin-4-one (84). 

Various alkylating agents are used for the preparation of pyridazinyl alkyl sulfides. Methyl and ethyl iodides, dimethyl and diethyl sulfate, a-halo acids and esters, /3-halo acids and their derivatives, a-halo ketones, benzyl halides and substituted benzyl halides and other alkyl and heteroarylmethyl halides are most commonly used for this purpose. Another method is the addition of pyridazinethiones and pyridazinethiols to unsaturated compounds, such as 2,3(4//)-dihydropyran or 2,3(4//)-dihydrothiopyran, and to compounds with activated double bonds, such as acrylonitrile, acrylates and quinones. 

Diethyl sulfate [64-67-5] M 154.2, b 96 /15mm, 118 /40mm, d 1.177, n 1.399. Washed with aqueous 3% Na2C03 (to remove acidic material), then distilled water, dried (CaCl2), filtered and distd. Causes blisters to the skin. 

N. N-diakyl amino Ethylamme Dibiitylphosphite Dicyandiamide Diethylammo ethanol Diethyl phosphite Diethyl sulfate Diketene... 

Ethanol-OD can also be prepared by hydrolyzing diethyl carbonate in the presence of deuterium oxide and diethyl sulfate in a similar way as described in section IX-A-2. 

Diethyl aniline, 54 Diethylcarbaniazine citrate, 54 Diethyl carbamyl chloride, 54 Diethyl chlorophosphate, 54 Diethylene triamine, 54 Diethyl ether, 54 Di(2-ethylhexyl) phthalate, 54 Diethyl ketone, 54 Diethyl-p-phenylenediamine, 54 Diethyl phthalate, 54 Diethylstilbestrol, 55 Diethyl sulfate, 55 Diethyl zinc, 55 Difluoromethane chloride, 55 Digitoxin, 55 Diglycidyl ether, 55 Digoxin, 55 Diisobutyl ketone, 55 Diisopropylamine, 55 Diisopropyl ether, 55 DIKAMIN , 2,4-D, 55 DIKONIRT , 2,4-D, 55 Dimefox, 55 Dimethoate, 55 3,3 -Dimethoxybenzidine, 55 n,n-Dimethylacetamide, 56 Dimethylamine, 56 4-Dimethylaminoazobenzene, 56 Dimethylaminoethanol, 56 n,n-Dimethyl aniline, 56 7,12-Dimethylbenz[a]anthracene, 56 3,3 -Dimethylbenzidine, 56... 

---