Sulfuric acid, reaction with diethyl

Fig. 2. Synthesis of uma2enil (18). The isonitrosoacetanihde is synthesized from 4-f1iioroani1ine. Cyclization using sulfuric acid is followed by oxidization using peracetic acid to the isatoic anhydride. Reaction of sarcosine in DMF and acetic acid leads to the benzodiazepine-2,5-dione. Deprotonation, phosphorylation, and subsequent reaction with diethyl malonate leads to the diester. After selective hydrolysis and decarboxylation the resulting monoester is nitrosated and catalyticaHy hydrogenated to the aminoester. Introduction of the final carbon atom is accompHshed by reaction of triethyl orthoformate to...

Sinha and co-workers reported that the reaction of the 3-bromometh-ylquinazolines 127 and CH acid compounds 128 gave rise to 129, which were converted by heating in 2 iV sulfuric acid or in polyphosphoric acid to the pyrrolo[ 1,2-a]quinazolines 130 and 131. Reaction with diethyl malonate afforded the l-oxopyrrolo[l,2-a]quinazolines 130, whereas other CH acid compounds (128) gave the pyrrolo[l,2-a]quinazolines 131. When 129 (R = Me, R = COMe, X = O) was heated in polyphosphoric acid, the ring closure reaction was accompanied by deacetylation and led to the pyr-rolo[ 1,2-a]quinazoline 131 (R = COMe, R = H, X = O). Ring closure did not occur in acetic anhydride. ... 

When applied to the synthesis of ethers the reaction is effective only with primary alcohols Elimination to form alkenes predominates with secondary and tertiary alcohols Diethyl ether is prepared on an industrial scale by heating ethanol with sulfuric acid at 140°C At higher temperatures elimination predominates and ethylene is the major product A mechanism for the formation of diethyl ether is outlined m Figure 15 3 The individual steps of this mechanism are analogous to those seen earlier Nucleophilic attack on a protonated alcohol was encountered m the reaction of primary alcohols with hydrogen halides (Section 4 12) and the nucleophilic properties of alcohols were dis cussed m the context of solvolysis reactions (Section 8 7) Both the first and the last steps are proton transfer reactions between oxygens... 

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). 

Isoxazole was first synthesized by Claisen in 1903 from propargylaldehyde diethyl acetal and hydroxylamine (03CB3664). It has also been obtained by addition of fulminic acid to acetylene in methanol-dilute sulfuric acid solution, by acidic hydrolysis of 5-acetoxyisoxazo-line, by reaction of /S-chloroacrolein or/3-alkoxyacrolein with hydroxylamine hydrochloride... 

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). 

Diethyl ether and other simple symmetrical ethers are prepared industrially by the sulfuric acid-catalyzed dehydration of alcohols. The reaction occurs by SN2 displacement of water from a protonated ethanol molecule by the oxygen atom of a second ethanol. Unfortunately, the method is limited to use with primary alcohols because secondary and tertiary alcohols dehydrate by an El mechanism to yield alkenes (Section 17.6). 

Benzene and naphthalene compounds can be formylated under Vil-smeir conditions. The formyl compounds, with or without isolating, can be condensed with amino arenes to give leuco compounds. In this reaction, the benzhydrol intermediate is not isolated.21,79,84 86 The reaction is generally carried out in an alcohol solvent such as isopropanol, butanol, or pentanol and an acid catalyst such as hydrochloric acid, sulfuric acid, or methanesul-fonic acid.87 Acetic acid can also be used both as catalyst and as the solvent. Urea sometimes is added as catalyst.84,88 Terephthaldehyde reacts with W-diethyl-3-methylaniline89 and substituted azulenes to give a bis-triphenylmethane21 57 and 58, respectively. 

Pure parathion is a pale yellow, practically odorless oil, which crystallizes in long white needles melting at 6.0° C. (17). It is soluble in organic solvents, except kerosenes of low aromatic content, and is only slightly soluble in water (15 to 20 p.p.m. at 20° to 25° C.). Peck (35) measured its rate of hydrolysis to diethyl thiophosphate and nitro-phenate ions in alkaline solutions. He found that the reaction kinetics are first order with respect to the ester and to hydroxyl ion. In normal sulfuric acid the rate of hydrolysis was the same as in distilled water. Peck concluded that hydrolysis takes place by two mechanisms—a reaction catalyzed by hydroxyl ions and an independent uncatalyzed reaction with water. He calculated that at a pH below 10 the time for 50% hydrolysis at 25° C. is 120 days in the presence of saturated lime water the time is 8 hours. The over-all velocity constant at 25° C. is k = 0.047 [OH-] + 4 X 10-6 min.-1... 

Cyclobutylcyclopropanol [133] To a well-stirred solution of ethyl cyclobutanecarboxylate [134] (56.47 g, 0.441 mol) and titanium tetraisopropoxide (26.3 mL, 88.2 mmol, 20 mol%) in anhydrous diethyl ether (200 mL), ethylmagnesium bromide (0.980 mol, 276 mL of a 3.55 m solution in Et20) was added over a period of 3 h. The temperature was maintained at between 20 and 25 °C with a water bath. After the addition was complete, the mixture was stirred for an additional 0.5 h at the same temperature, then cooled to —5 °C, whereupon the reaction was quenched by the careful addition of ice-cold 10 % aqueous sulfuric acid (500 mL) while the temperature was maintained between —5 and 0°C with an acetone/dry ice bath. The mixture was stirred at 0°C for an additional 1 h and then the aqueous phase was extracted with Et20 (100 mL). The combined ethereal phases were washed with saturated aq. NaHC03 solution (2 X 200 mL) and brine (200 mL), dried, and concentrated at water-pump pressure at 20 °C to give 48.92 g (99%) of 1-cyclo-butylcyclopropanol. The spectroscopic data of the product were identical to those reported in the literature [135]. 

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