Nitroethanol

In a 5-1., three-necked, round-bottomed flask fitted with a 30-ml. dropping funnel, mechanical stirrer, and thermometer extending down into the liquid is placed a suspension of paraformaldehyde (trioxymethylene, 125 g., 4.16 moles) in freshly distilled (Note 1) nitromethane (2.5 1., 46.6 moles). The suspension is stirred vigorously, and 3N methanolic potassium hydroxide solution is added dropwise from the dropping funnel until, at an apparent pH of 6-8, but closer to pH 8 (pH paper), the paraformaldehyde begins to dissolve and the suspension assumes a clearer appearance. About 10 ml. of the alkaline solution is required, and the addition takes about 10 minutes. About 15-20 minutes after addition of the alkaline solution is complete, the paraformaldehyde dissolves completely. Shortly thereafter, the solution temperature reaches a maximum of 13-14 degrees above room temperature and then slowly drops. Stirring is continued 1 hour after addition of the alkaline solution is complete. 

Stirring is continued while the added alkali is completely neutralized by adding concentrated (361V) sulfuric acid (1 ml.) drop-wise from a medicine dropper over a period of about 3 minutes until an apparent pH of about 4 is reached (Note 2). The solution is then stirred for an hour, during which time the pH should not change (Note 3). 

The precipitated potassium sulfate is filtered by passing the solution through a 12-cm. Buchner funnel. The light-yellow or yellowish green filtrate is transferred to a 5-L, one-necked, round- 

The two-phase main fraction of the distillate is placed in a 500-ml. separatory funnel and the lower layer of crude 2-nitroethanol (185-200 g., 146-158 ml., d 1.4493-1.4513, containing about 92-94 mole % 2-nitroethanol) is drawn off. The 2-nitroethanol is then extracted in a 500-ml. separatory funnel with an 

Commercial nitromethane is sometimes quite acidic, and much more methanolic potassium hydroxide is required to initiate the reaction when such material is used. For safety, the nitromethane should be distilled at aspirator pressure instead of atmospheric pressure. 

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Distilling 2-nitroethanol gave rise to a detonation, which was explained by the accidental presence of a base in the distillation apparatus. 

Figure 5-3. Biocides bromo-2-nitropropane, 1-N-hexadecyl-1,2,4-tri-azole bromide, 3-hydroxy-4-methylthiazol-2(3H)-thione, 3-hydroxy-4-phenylthiazol-2(3H)-thione, 2,3-dibromo-1-chloro-4-thiocyanato-2-butene, 1,2-dibromo-2,4-dicyanobutane, 2,2-dibromo-2-nitroethanol.

Interaction of nitromethane and formaldehyde in presence of alkali gives not only 2-nitroethanol, but also di- and tri-condensation products. After removal of the 2-nitroethanol by vacuum distillation, the residue must be cooled before admitting air into the system to prevent a flash explosion or violent fume-off. 

An explosion occurred towards the end of vacuum distillation of a relatively small quantity of 2-nitroethanol. This was attributed to the presence of peroxides, but the presence of traces of alkali seems a possible alternative cause. 

The reaction of alkynes with nitric acid or mixed acid is generally not synthetically useful. An exception is the reaction of acetylene with mixed acid or fuming nitric acid which leads to the formation of tetranitromethane. A modification to this reaction uses a mixture of anhydrous nitric acid and mercuric nitrate to form trinitromethane (nitroform) from acetylene. Nitroform is produced industrially via this method in a continuous process in 74 % yield. " The reaction of ethylene with 95-100 % nitric acid is also reported to yield nitroform (and 2-nitroethanol). The nitration of ketene with fuming nitric acid is reported to yield tetranitromethane. Tetranitromethane is conveniently synthesized in the laboratory by leaving a mixture of fuming nitric acid and acetic anhydride to stand at room temperature for several days. ... 

The reaction of a -halocarboxylic acids with sodium nitrite has been used to synthesize ni-tromethane, nitroethane and nitropropane, although the reaction fails for higher nitroalkanes. " A number of other reactions have been reported which use nitrite anion as a nucleophile, including (1) reaction of alkyl halides with potassium nitrite in the presence of 18-crown-6, (2) reaction of alkyl halides with nitrite anion bound to amberlite resins, (3) synthesis of 2-nitroethanol from the acid-catalyzed ring opening of ethylene oxide with sodium nitrite, and (4) reaction of primary alkyl chlorides with sodium nitrite in the presence of sodium iodide. ... 

Like nitromethane, 2-nitroethanol can be used as the methylene component for addition to aldehydes, giving epimeric nitrodiols in which the carbon chains have been lengthened by two carbon atoms. This reaction has attained preparative importance for the S5mthesis of higher-carbon ketoses 43,44) heptulose-phosphates 5) and of chloramphenicol... 

For the cyclization of dialdehydes, however, its utility seems limited. Being a nitromethane addition product, it can readily undergo retro-nitromethane addition with alkali to give formaldehyde and nitromethane. Thus, it is not surprising that reaction of glutaraldehyde with 2-nitroethanol under the usual conditions (i.e. 1 molar equivalent of sodium hydroxide in aqueous ethanol) should yield 2-nitrocyclohexane-1,3-diol 5), a nitromethane cyclization product With catal5dic amounts of sodium hydroxide (pH 8—9), however, 1-hydroxymethyl-l-nitro-cyclohexane-2-6-diol (80) can be isolated in yields of 24—29%... 

The second method consists of the condensation of diacetate of the same aldehyde with nitromethane, which forms (3,4-diacetoxyphenyl)-2-nitroethanol (11.1.5). Then the nitro group is reduced and the product (11.1.6) is hydrolyzed into the desired norepinephrine (11.1.4) [4,9,13,14]. 

V.M. Bashinova, NeftepererabNeftekhim 1, 21—3 (196S)(Russ) CA 68, lO4503(1968)(Phys props of 2-Nitroethanol) 11) Ibid, ZhPriklKhim 41 (8),... 

EthanoJ,2-Nitronitrate 2-Nitroethanol Nitrate l-Nitroxy-2-nitroethane or 9-Nitroethyl Nitrate,... 

The crude Kekule oil, when freed from admixed and dissolved acid by washing with water, contd 40—50% 2-Nitroethanol Nitrate and 50—40% Nitroglycol. On shaking the oil with very dil caustic alkali, the Nitroethanol Nitrate is removed leaving pure Nitroglycol. Numerous patents have been issued for processes of procuring pure Nitroglycol from Kekule oil (Refs 4 5)... 

Ethanol, 2-NitTonitrite 2-Nitroethanol Nitrite l Nitrosoxy-2-nitroetbanol or fi-Nttraetbyl-alcohol Nitrite, O2N.CH2.CH2.ONO mw 120.065, N 23-33%, OB to C02 -26.6% not found in the open literature Refs 1) Beil, not found 2) CA, not found... 

The 2-nitroethanol obtained by this procedure is quite satisfactory for synthetic purposes, such as the preparation of nitro-ethylene. The small amount of light petroleum ether dissolved in the 2-nitroethanol can easily be removed under reduced pressure. Most of the remaining diphenyl ether can be removed by one redistillation under vacuum, since the fore-run is relatively rich in diphenyl ether. The main fraction has n-u 1.4425-1.4431. Although vacuum redistillation of 2-nitroethanol which has been freed by the present procedure from higher condensation products of formaldehyde with nitromethane is relatively safe, it is recommended that the procedure be carried out behind a safety shield or a barricade. 

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