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		Rhodium (Chief Bee) 09-11-01 09:08 No 212002				Easy nitroethane in quantitative yield
						US Pat 4,319,059 This patent shows an easy route from alpha-bromopropionic acid to nitroethane in excellent yield. The patent also say that Magnesium chloride, bromide or sulfate may be used instead of the magnesium methoxide, but it doesn't say if this affects yields. The reaction proceeds as follows: In the polar aprotic solvent DMSO, the alpha-bromopropionic acid reacts in an SN2 fashion with nitrite ion to give alpha-nitropropionic acid and bromide ion. The role of the Mg2+ ion in the reaction is to facilitate the decarboxylation (removal of CO2) from the intermediate nitro acid, as it forms a chelate between one of the oxygen atoms on the nitro group and the oxygen anion of the carboxylic acid. The electron-withdrawing nature of the nitro group makes the carboxylic acid group labile, and it can easily be given off as carbon dioxide. If magnesium methoxide is used in place of the other magnesium salts, the carboxylic acid is directly deprotonated, probably making the reaction go even faster. There is no workup mentioned in the patent, but I'd suggest flooding with water (or using large amounts of dilute (5%) HCl in the hydrolysis step), and then extract the nitroethane with dichloromethane, ether or possibly petroleum ether. Then the combined organic layers are washed first with water and then with a concentrated NaCl solution, followed by drying the organic phase over anhydrous MgSO4, which is then filtered off. Then the solvent is removed distilled, and the residual crude nitroethane is fractionally distilled at 114-115°C. alpha-Bromopropionic acid can be made from propionic acid and phosphorous tribromide (from red phosphorous and bromine, the Hell-Volhard-Zelinsky reaction, http://www.geocities.com/chempen_software/reactions/RXN099.htm or http://www.orgsyn.org/orgsyn/default.asp?formgroup=base_form_group&dbname=orgsyn), or by HBr bromination of lactic acid (alpha-hydroxypropionic acid). Example 1 To a mixture of magnesium methoxide (0.11 mole) and dimethyl sulfoxide (50 ml) a-bromopropionic acid (0.11 mole) was added at 20°C. with stirring. To this mixture a solution of sodium nitrite (0.145 mole) in dimethyl sulfoxide (65 ml) was added at room temperature. Then, the reaction mixture was stirred at room temperature for 6 hours and was neutralized upon addition of diluted hydrochloric acid. Analysis of the reaction mixture indicated more than 99% conversion of alpha-bromopropionic acid and 94.5% yield of nitroethane. Example 2 In the manner of Example 1, sodium nitrite, alpha-bromopropionic acid and magnesium methoxide were reacted in dimethyl sulfoxide as the aprotic solvent. The reaction time was 2 hours for one run and 22 hours for another. Reaction was conducted at room temperature. The run at 2 hours converted only 94.5% of the acid and yielded 72.7% nitroethane. The second run at 22 hours gave a conversion of > 99% and a yield of 100%. At room temperature the reaction apparently takes about 4-5 hours to go to completion. At higher temperatures of 40°C. up to about 75°C. the reaction time is shorter. Thus, one or two hours or even less time at 75°C. will completely convert the bromoacid to the intermediate which can then be decomposed to the nitroalkane. When using dimethyl sulfoxide as solvent temperatures approaching 100°C should be avoided since the solvent will volatilize and decompose at about 100°C. Other aprotic solvents may not have this disadvantage.



		Osmium (Stoni's sexual toy) 09-11-01 13:37 No 212032				Re: Easy nitroethane in quantitative yield
						Nice. Some ideas regarding the workup: Flooding with water and extracting is tedious and wasteful, and requires other solvents. Since EtNO2 forms azeotropes with all kinds of different solvents selecting the wrong one will cause a lot of headaches. I came up with the following variations, which should work theoretically: 1) When the reaction is finished neutralise with another (organic?) acid which doesn´t contain any or only a little water. Then add a solvent known to form an azeotrope with EtNO2 and distill out that azeotrope. I think the lower alcohols should work ok for this step. Then you can either separate the EtNO2 by flooding with water, extracting the EtNO2 and recycling the alcohol by distillation. Any EtNO2 not extracted will distill over with the alcohol, and by reusing it you will limit EtNO2 losses during the next workup. Well, that isn´t really an improvement over the workup suggested above, so why not simply use the alcohol/EtNO2 mixture for your desired reaction. When the azeotrope composition is high enough in EtNO2 it can be directly used in nitropropene syntheses, which often use an alcohol co-solvent anyway. 2) I think this is the best way to go: After neutralising apply vacuum and distill the EtNO2 directly out of the reaction mixture. The vacuum requirements aren´t high, all you want to do is depress the EtNO2 boiling point enough so it will be around 60-80°C. or you pull a little more vacuum and simply rotovap the EtNO2 off By using another dipolar-aprotic solvent like DMF one be able to distill the EtNO2 without vacuum. If that reaction could be made catalytic in Mg(OMe)2, it might even be possible to distill the EtNO2 out as soon as it is formed, either under vacuum or with no vacuum at all, which should speed up the reaction even more due to the elevated temperature.



		Rhodium (Chief Bee) 09-11-01 14:39 No 212043				Re: Easy nitroethane in quantitative yield
						Nitroethane does not form an azeotrope with DCM, as was pointed out by someone earlier, so I still think that would be a good idea. The nitroethane will definitely travel over to the DCM layer rather than staying in a DMSO/H2O mixture. The water/brine washes of the organic layer is to remove carried over DMSO (but that may not be necessary, just distill after drying the organic layer).