Ethyl isopropyl ether, preparation

Problem 14.55 Prepare the following ethers starting with benzene, toluene, phenol (C H OH), cyclohexanol, any aliphatic compound of three C s or less and any solvent or inorganic reagent a) dibenzyl ether, b) di-/i-butyl ether, (c) ethyl isopropyl ether, d) cyclohexyl methyl ether, (e) p-nitrophenyl ethyl ether, (/) divinyl ether (g) diphenyl ether. <... 

An unsymmetrical ether can usually be prepared by two different Williamson ether syntheses. For example, the preparation of ethyl isopropyl ether could be accomplished by the reaction of ethoxide ion (nucleophile) with isopropyl bromide (electrophile) or by the reaction of isopropoxide ion (nucleophile) with ethyl bromide (electrophile), as shown in Figure 10.2. Which of these routes is better Because alkoxide ions are strong... 

Methylsulfinyl -pentyl ketone is prepared by the reaction of the reagent (0.1 mole) and 7.2 g (0.05 mole) of ethyl caproate yielding the crude product as a pasty crystalline mass. The material is dissolved in hot isopropyl ether (20 ml), petroleum ether (30 ml) is added, and the solution cooled to -15°. Filtration yields approx. 6 g of white plates, mp 40-44°. Recrystallization from isopropyl ether affords pure product, mp 45-47°. 

Methylsulfinyl cyclohexyl ketone is prepared by reaction of the reagent (0.08 mole) with 6.24 g (0.04 mole) of ethyl cyclohexanecarboxylate yielding about 7 g of product, mp 62-63° after recrystallization from isopropyl ether. 

Preparation of 4-aza-S-(N-methyl-4-piperidyll-10,11-dihydro-SH-dibenzo[a,d]cycloheptene-S-ol Add 17.4 g of N-methyl-4-chloropiperidine to a stirred mixture containing 3.2 g of magnesium, 20 ml of anhydrous tetrahydrofuran, 1 ml of ethyl bromide and a crystal of iodine. Reflux for two hours, cool to 30°-35°C and add a solution of 13 g of 4-aza-10,11 -dihydro-5H-dibenzo[a,d] cycloheptene-5-one in 25 ml of tetrahydrofuran. Stir for five hours, remove the solvent by distillation in vacuo and add 250 ml of ether. Add 100 ml of 10% ammonium chloride solution and extract the mixture with chloroform. Concentrate the chloroform solution to a residue and recrystallize from isopropyl ether obtaining 20 g of the carbinol,... 

Preparation of 4-( -Chloroethyl)-3,3-Diphenyl-1Ethyl-2-Pyrrolidinone A solution of a,a -diphenyl-a -(1-ethyl-3-pyrrolidyl)-acetonitrile in 70% sulfuric acid was heated at 130°-140°C for 48 hours, poured onto ice, made basic with sodium hydroxide, and extracted with chloroform. The chloroform solution was acidified with hydrogen chloride gas, dried over sodium sulfate and concentrated. The residue was refluxed in 500 ml of thionyl chloride for 3 hours the resulting solution was concentrated in vacuo and the residue was crystallized from isopropyl ether. 

Methylation of alkaloids containing either phenolic hydroxy groups or secondary amine functions is the most common procedure for converting such alkaloids to known derivatives many examples are given in Section II,C. Diazomethane is the reagent of choice for O-methylation, and diazoethane for O-ethylation. It is possible to effect O-alkylation in the presence of secondary amine functions, as in the conversion of peinamine to its trideuteriomethyl ether (Section II,C,92) and of A-desmethylthalrugosidine to the O-ethyl ether (Section II,C,29). Another O-alkylation method, exemplified by the preparation of O-methyl, O-ethyl, and O-isopropyl ethers of berbamine (364), consisted of heating the alkaloid in... 

The above procedure is based on that described by Adams, Abramovitch, and Hauser.1 Ethyl a-isopropylacetoacetate has also been prepared by Hauser and B reslow2 by the reaction of ethyl acetoacetate with isopropyl ether in the presence of boron trifluoride and by Bischoff 3 by the alkylation of the sodium derivative of ethyl acetoacetate with isopropyl iodide. 

This is prepared from 4-(A -benzylamino)isoxazole by the same procedure as for A -(4-isoxazolyl)formamide above. Thus, reaction of 4-(A7-benzylamino)isoxazole (0.843 g, 4 mmol) gives, after flash chromatography [34] (ethyl acetate-isopropyl ether, 2 8), a yellow solid (0.714g, 88%), m.p. 71-73 C. 

Aliphatic Ethers. The aliphatic ethers used in industry are made usually by the action of sulfuric acid on an alcohol. Ethyl ether and isopropyl ether are thus prepared. However, more ethyl ether than the market usually absorbs is obtained as a by-product of the hydration of ethylene to alcohol. Alkyl halides react on a hydroxyl group either directly, in the presence of an alkali, or after the hydrogen of a hydroxyl group has been replaced by sodium. This is the Williamson synthesis which is particularly applicable to making mixed ethers ... 

Fig. 3 Effect of cholesteryl ethers in liposomes prepared with DOPC on the relative amount of glucose released (A) (x) cholesterol (o) cholesteryl methyl ether ( ) cholesteryl ethyl ether (v) cholesteryl-n-propyl ether ( ) cholesteryl isopropyl ether (A) cholesteryl butyl ether (B) (x) cholesterol (o) cholesteryl (2 -hydroxy)-3-ethyl ether ( ) cholesteryl methoxy methyl ether ( ) cholesteryl acetate.

Dimenhydrinate. Dimenhydrinate [523-87-5] (Dramamine) (18) is a white crystalline, odorless powder that melts between 102 and 107°C. It is sparingly soluble in water, freely soluble in ethanol and chloroform, and sparingly soluble in diethyl ether. Dimenhydrinate is prepared by combining dimethylaminoethyl ben2hydryl ester with 8-ch1orotheophy11ine and refluxing in an isopropyl alcohol solution. The crystalline precipitate of dimenhydrinate that forms on cooling is collected by filtration, washed with cold ethyl acetate, and dried. 

Anhydrous stannous chloride, a water-soluble white soHd, is the most economical source of stannous tin and is especially important in redox and plating reactions. Preparation of the anhydrous salt may be by direct reaction of chlorine and molten tin, heating tin in hydrogen chloride gas, or reducing stannic chloride solution with tin metal, followed by dehydration. It is soluble in a number of organic solvents (g/100 g solvent at 23°C) acetone 42.7, ethyl alcohol 54.4, methyl isobutyl carbinol 10.45, isopropyl alcohol 9.61, methyl ethyl ketone 9.43 isoamyl acetate 3.76, diethyl ether 0.49, and mineral spirits 0.03 it is insoluble in petroleum naphtha and xylene (2). 

N-ethyl-3-chloropiperidine was prepared according to the method of Fuson and Zirkle described in Volume 70, J. Am. them. Soc., p 2760. 12.0 g (0.0B1 mol) of N-ethyl-3-chloropiperidine was mixed with 1B.6 g (0.0B1 mol) of benzilic acid and 80 cc of anhydrous isopropyl alcohol as a solvent. The mixture was refluxed for 72 hours. The solution was then filtered and concentrated at 30 mm of mercury. The concentrate was dissolved in water, acidified with hydrochloric acid and extracted with ether to remove the unreacted benzilic acid. 

A mixture of 349 mg (1 mmol) of (3S.6S,7aS)-6-benzyl-tetrahydro-3-isopropyl-6-methyl-7a-phenylpyrro-lo[2.1 -A oxazol-5(6//)-one (9, R2 = f-Pr R4 = CH3) and 10 mL of 48% aq hydrobromic acid is heated at reflux for 24 h. After cooling to r.t., the solution is diluted with water and extracted with three portions of ethyl acetate. The combined extract is dried over anhyd Na2S04. filtered and concentrated in vacuo, and the residue is dissolved in diethyl ether. The ethereal solution is treated with excess diazomethane in diethyl ether, and the solution is filtered and concentrated. The residue is purified by preparative TLC and distilled bulb-to-bulb to give a colorless oil yield 233 mg (85%) 100% ee bp 120sC/0.07 Torr [a]D +12.8 (c = 1.2. CHC13). 

The present procedure is the best way of preparing aliphatic isocyanides boiling above ethyl isocyanide. It has been applied to the synthesis of the following isocyanides 6 isopropyl (38%), -butyl (61%), te -butyl (68%), and benzyl (56%). In preparing isopropyl isocyanide or teri-butyl isocyanide, the petroleum ether should be of boiling point 30-35°, as otherwise it is difficult to separate these low-boiling isocyanides in the indicated yield, and,... 

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