Ethyl ether, reaction with diazomethane

Aleuritic acid [RX-erj Aro-9,10,16-trihydroxyhexadecanoic acid] [533-87-9] M 304.4, m 100-101 , pKsst 4.9. Crystallise this / S-acid from aqueous EtOH. It is soluble in MeOH, and forms a less soluble crystalline sodium salt. The methyl ester m 72-73°, b 235°/0.2mm, is best prepared by reaction with diazomethane and forms fine feathery needles it is soluble in MeOH, EtOH, CHCI3, Mc2CO, slightly soluble in CgH6 and insoluble in petroleum ether. The ethyl ester [6003-09-4] m 59°, crystallises in needles from EtOH. The hydrazide [6003-10-7] crystallises from EtOH and has m 139-140°. 

Methyl esters are prepared by reaction with diazomethane, dissolved in petroleum ether and added to the column. Hydrocarbons are eluted with 150-200 mL petroleum ether. Alkenesulfonates are eluted with 500 mL 90 10 petroleum ether/ ethyl ether and hydroxyalkane sulfonate and all disulfonates are eluted with 500 mL ethyl ether. Unesterified material is removed with 50 50 ethyl ether/MeOH. 

While Kakisawa et al. (87TL3981) reported formation of Wmethylpyrazole 1, Yamaguchi et al. obtained the NH derivative 2 by reaction of caryoynencins with diazomethane in ethyl acetate at 0°C (94BSJ1717 95JMC5015). The 1,3-dipolar addition was quite sensitive to the solvent employed, and a very low yield of pyrazole derivative 2 was obtained in ether or methanol (Scheme 5). 

The residue was subjected to azeotropic operation with toluene two times, and ether was added to the residue. The precipitate derived from trioxane was removed by filtration and washed with ether, and the combined ethereal solutions were concentrated under reduced pressure. The residue was dissolved in ethyl acetate, and the solution was washed with water and aqueous saturated solution of sodium chloride, was dried, and was concentrated to give 4 g of an oily material. The oily material was dissolved in 20 ml of methanol and to the solution was added 20 ml of aqueous 1 N solution of sodium hydroxide, and the mixture was stirred for 14 hours at room temperature. After removal of methanol under reduced pressure, water was added to the mixture, and this solution was acidified to pH 3 with aqueous 2 N hydrochloric acid. The mixture was extracted five times with ethyl acetate, and the ethyl acetate extract was dried and concentrated to give 3.5 g of crude crystals. After addition of ethanol to the crude crystals, the crude crystals were filtered. The filtrate was concentrated, and to the residue was added ethanol and ethyl acetate, and precipitate was collected by filtration. The combined amount of the crude crystals was 1.6 g. After the combined crude crystals were methylated with diazomethane, the reaction product was dissolved in 20 ml of ethyl acetate. To this solution was added 1.5 g of sodium acetate and 300 mg of 10% palladium-carbon, and the mixture was stirred for 2 hours under hydrogen. Then, the reaction product was filtered, and after addition of aqueous saturated solution of sodium hydrogen carbonate to the filtrate, the mixture was extracted two times with ethyl acetate. The extract was washed with an aqueous saturated solution of sodium chloride, dried, and concentrated to give 1.3 g of crude crystals. The crude crystals were recrystallized from ethyl acetate to yield 765 mg of the title compound (melting point 134-135°C, yield 43%). 

To a solution of 390 mg of 4-[3-methyl-trans-4a-cisoid-4a,5a-cis-5a-l,4a,5,5a,10b,10c-hexahydro-7-dioxino[5,4-a]cyclopenta[b]benzofuranyl] butyric acid in 5 ml of ethyl acetate cooled in an ice bath was added an excess of an ethereal solution of diazomethane, and after being stirred for 5 min the mixture was concentrated. The resulting oily material was dissolved in 3 ml of methanol, and to the solution was added 1 ml of 1 N hydrochloric acid and the mixture was stirred for 3 hours at room temperature. After concentration of the reaction mixture and addition of 1 ml of water, the mixture was extracted 3 times with each 5 ml of ethyl acetate. The combined layers of ethyl acetate were washed with 3 ml of water and 3 ml of aqueous saturated solution of sodium chloride, dried and concentrated to give 380 mg of crude crystals. The crude crystals were recrystallized from ethyl acetate-hexane to yield 200 mg of the pure captioned product (m.p. 56-57°C, yield 53%). 

Other acyl alkyl esters have been utilized only sporadically. Makita et al. [241] analysed N-isobutyloxycarbonyl methyl esters of protein amino acids. During the first step of the preparation, the amino group reacts with isobutyl chloroformate according to Scheme 5.21. The reaction is accomplished in 10 min in an aqueous medium in the presence of sodium carbonate at room temperature. Excess of the reagent is extracted with diethyl ether and the reaction mixture is saturated with NaCl, acidified with ortho-phosphoric acid to pH 1—2 and extracted with diethyl ether. Methanol is added to the ethereal extract and the carboxyl group is esterified with diazomethane at room temperature for 5 min, The solvent is removed under a stream of nitrogen at 50°C and the residue is dissolved in ethyl acetate. Arg does not provide a volatile derivative when sub-... 

The reactions of diazomethane with C- and X-substituted alkenes are much slower, and consequently there are fewer known examples. The slower rate of reaction is explained easily by the larger energy separation in the frontier orbitals (10 and 9.8 eV, respectively, in Fig. 6.34). The regioselectivity, however, is the same A -pyrazolines like 6.225 and 6.227 with the substituent at C-3 are obtained with both C- and X-substituted dipolarophiles. This at first sight surprising observation can be explained by the change from dipole-HO-control in the cases of the Z- and C-substituted alkenes 6.223 and 6.224 to dipole-LU-control 6.226 in the case of the X-substituted alkene ethyl vinyl ether. 

Different competitive processes are dependent on the diazo compound, on the unsaturated system, and on the solvent. With 1,1,1-trifluorobutan-2-one and diazomethane, the corresponding oxirane is formed almost exclusively. While methyl trifluoropyruvatc reacts with diazomethane to provide a mixture of the oxiranes, reaction of the pyruvate with ethyl diazoacetate provides a stable [3-1-2] cycloadduct.Chiral fluoroalkyl-substituted /i-oxo sulfoxide (e.g., 1) readily react with diazomethane to provide the corresponding chiral epoxides. Use of methanol as solvent favors oxirane formation over the competitive enol ether formation. 

Methylation with methyl iodide (93) or diazomethane (86) yields dl-laudaiiosine (XIII). Likewise, ethylations with ethyl iodide, ethyl sulfate (84), or diazoethane furnish 3 -ethyllaudanine. Oxidation of this ethyl ether ruptures the molecule, and Spath (86) was able to isolate 3-ethoxy-4-methoxybenzoic acid from the reaction mixture, thus locating the position of the hydroxyl group in laudanine. 

Phenyldiazomethane has been used to make benzyl esters, specifically for avoiding the risk of evaporative losses where lower esters might be too volatile. It can be made from azibenzil [64] or from N-benzyl-N-nitroso-p-toluenesulphonamide [65-69]. It is kept as a red solution, 50% in either ethyl ether or petroleum ether, and as with diazomethane, disappearance of the red colour is used to indicate the completeness of the reaction. The analogous diazobenzene can be made in much the same way from N-phenyl-N-nitrosourea [68]. It is used to make phenyl esters in the same way as benzyl esters are made with phenyldiazomethane. Finally, pentafiuoro-... 

Preparation by reaction of diazomethane with 2,4,6-trihydroxy-3-methylbenzo-phenone in ethyl ether (86%) [806]. 

Also obtained by reaction of diazomethane with 4-hydroxy-3-nitroacetophenone in ethyl ether [3938]. 

Obtained by reaction of diazomethane with 2,4,6-trihydroxy-3-(3-methyl-2-butenyl)- acetophenone in ethyl ether [4335], (90%) [4359], (20%) [4322]. Also obtained by reaction of prenyl bromide with 2-hydroxy-4,6-dimethoxyac-etophenone in the presence of potassium carbonate in refluxing acetone for 8 h [4360,4361]. 

Also obtained by decomposition of l-(2,4-diacetoxyphenyl)-2-diazoethanone in methanol with copper bronze (43%). The diazoketone (brownish yellow glassy solid) was prepared by reaction of diazomethane with 2,4-diacetoxybenzoyl chloride in ethyl ether [4820]. 

COCH2CH3 - Obtained by reaction of 2-propionyl-1,3-indandione with diazomethane in ethyl ether (66-72%) [7813]. 

Preparation by reaction of diazomethane with phloroisobutyrophenone in ethyl ether at 0° for 5 days (59%) [8051]. 

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