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Nitroethane Synthesis: A Compilation

by Aurelius (format & minor edits by metanoid)
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here's what available on the hive, thus far:

Nitroethane synthesis: a compilation

Method 1:   from sodium ethyl sulfate and a metal nitrite

1.5 mole sodium nitrite (103.5g) is intimately mixed with 1 mole of sodium ethyl sulfate (158g) and 0.0625 moles of K2CO3 (8.6g).   The mixture is then heated to 125-130C, at which temperature the nitroethane distills over as soon as it is formed.   The heating is discontinued when the distillation flow slackens considerably, and the crude nitroethane is washed with an equal amount of water, dried over CaCl2, and if needed, decolorized with a little activated carbon.   The nitroethane is then re-distilled, collecting the fraction between 114-116C.   Yield 46% of theory

(another ref says max.   42%)
Chemical Abstracts, Vol 49, pg 836.

Method 2:   from diethyl sulfate and sodium nitrite

Initial run - Into a stoppered bottle was placed a mixture of diethyl sulfate (120g) and sodium nitrite solution (120g in 160ml of water.) The bottle was shaken mechanically for 20 hours, the pressure being released at intervals.   The contents were then poured into a separating funnel, and the upper layer separated, dried over calcium chloride. and distilled at 14 mmHg, the distillate up to 60C being collected (the residue, ca.   230g., consisted of ethyl sulphate and was used again).   The distillate was fractionated at atmospheric pressure, and the fraction of bp 114-116C collected.   This was shaken with water, dried over calcium chloride, run through charcoal, and redistilled; bp 114-115.5C.   Yield, 17.7g.   (31%, or allowing for recovered ethyl sulfate, 43.5%).

Routine run - A second experiment was then carried out using the same quantity of ethyl sulfate as above.   The recovered nitrite solution (lower layer) from the first run was concentrated by adding approximately 16 g. of sodium nitrite per 160ml of solution.   Yield 26.4g (46%, or allowing for recovered ethyl sulphate, 65%).   For each additional subsequent run approximately 16 g. of nitrite per 160 ml of solution were added, although this represents a rather diminishing concentration in view of the increased yield of nitroethane


Method 3:   from ethyl bromide (iodide) and sodium nitrite (dmf)
32.5 grams of ethyl bromide (0.3 moles) was poured into a stirred solution of 600ml dimethylformamide and 36 grams dry NaNO2 (0.52 mole) in a beaker standing in a water bath keeping the solution at room temperature as the reaction is slightly exothermic.   Always keep the solution out of direct sunlight.   The stirring was continued for six hours.   After that, the reaction mixture was poured into a 2500 ml beaker or flask, containing 1500 ml ice-water and 100 ml of petroleum ether.   The petroleum ether layer was poured off and saved, and the aqueous phase was extracted four more times with 100 ml of petroleum ether each, where after the organic extracts were pooled, and in turn was washed with 4x75ml of water.   The remaining organic phase was dried over magnesium sulfate, filtered, and the petroleum ether was removed by distillation under reduced pressure on a water bath, which temperature was allowed to slowly rise to about 65C.   The residue, consisting of crude nitroethane was distilled under ordinary pressure (preferably with a small distillation column) to give 60% of product, boiling at 114-116C.

The ethyl bromide reacts with NaNO2, forming nitroethane and ethyl nitrite.
This method can be varied in a few ways.   Firstly, dimethyl sulfoxide (DMSO) can be substituted for the dimethylformamide (DMF) as solvent.   Ethylene glycol also works as solvent, but the reaction proceeds pretty sluggishly in this medium, allowing for side reactions, such as this: RH-NO2 + R-ONO => R-(NO)NO2 + R-OH.   KNO2 can also be used instead of NaNO2.   If NaNO2 is used in DMF, 30g (0.5 mol) of urea can also be added as nitrite scavenger to minimize side reactions, as well as simultaneously increasing the solubility of the NaNO2 and thereby significantly speeding up the reaction.

If the ethyl bromide is substituted with ethyl iodide, the required reaction time is decreased to only 2.5 h instead of 6 h.   In case ethyl iodide is employed, a slight change in the above procedure needs to be done.   The pooled pet ether extracts should be washed with 2x75ml 10% sodium thiosulfate, followed by 2x75ml water, instead of 4x75ml water as above.   This to remove small amounts of free iodine

Method 4 : from ethyl halide and silver nitrite

Cool 100 g of silver nitrite (0.65 mol) in 150 ml of dry ether to 0C in a 3 neck 500 ml flask (in a darkened room or using yellow light).   Add 0.5 moles of ethyl halide (78g ethyl iodide or 55g of ethyl bromide) dropwise over a 2 hour period while stirring constantly and maintaining the temperature at 0C and dark conditions.   Stir for 24 hours at 0C, then 24 hours at room temp if using ethyl bromide, and 48h if using ethyl bromide.   (Test for halogens to see when the reaction is completed, through adding a few drops of the reaction mixture to a test tube containing an alcoholic solution of silver nitrate and note if a precipitate appears.   If so, the reaction is not complete.   The Beilstein test can also be used, it uses a small coil of copper wire in a test tube to which a small portion of the reaction mixture is added and it is noted if reaction occurs, where elemental silver will deposit on the surface of the copper coil.) Silver iodide (or bromide) will precipitate in the solution during the course of the reaction.   Filter off the silver salt, and wash it with several portions of ether.   Evaporate the ether at room temperature.   (This may be substituted with distillation of the ether using a water bath at atmospheric pressure.   A 2x45 cm column packed with 4 mm pyrex helices is used.   A more efficient column is not used due to the instability of the ethyl nitrite formed as a by-product in the reaction.   Maintain anhydrous conditions since the ethyl nitrite will hydrolyze to ethanol and will be difficult to separate.) Then vacuum distill the residue at about 5 mmHg.   The ethyl nitrite will be the initial fraction, followed by an intermediate fraction, then the nitroethane will distill.   The yield is about 83% of theory


Method 5:   oxidation of ethyl amine with peracids(m-perbenzoicacid)

General Procedure for the Oxidation of Primary & Secondary amines using m-chloroperbenzoic acid.

m-Chloroperbenzoic acid (4.1g, 0.02mol, 85% pure) is dissloved in 30 mls of 1,2-dichloroethane in a three-neck flask equipped with a condenser and a pressure-equalising dropping funnel.   The amine (0.005 mol) in 3-5 mls of 1,2-dichloroethane solvent is added drop-wize to the refluxing m-Chloroperbenzoic acid/1,2-dichloroethane solution.   Refluxing temperature 83oC for 3 hours.
After the addition of the amine and refluxing time, the reaction mixture is cooled, filtered and washed with three 50 ml portions of 1M sodium hydroxide solution and dried over anhydrous magnesium sulphate.   The removal of the 1,2-dichloroethane solvent by distillation (rotary) gives a crude nitroalkane.   Purification of the crude crude nitroalkane with vacuum distillation.   Yields vary, approx 62 %.

Oxidation of n-propylamine and higher alkane amines give nitroalkane at approx 62 %.

[Note] Nitromethane and nitroethane form sodium water-soluable salts with 1M sodium hydroxide solution

Method 6:   oxidation of ethyl amine with potassium permanganate
Perhaps by the method in Org Synth CV 5, 845.

REFS for methods 5 + 6:


Chem.   Ber.   (1902) 35, 4294
Eur.   J.   Med.   Chem.   (1991) 26, 2, 167-178
Eur.   J.   Org.   Chem.   (1998) 4, 679-682
Heterocycles (1998) 48, 1, 181-185
J.   Amer.   Chem.   Soc.   (1954) 76, 4494
J.   Amer.   Chem.   Soc.   (1956) 78, 4003
J.   Amer.   Chem.   Soc.   (1957) 79, 5528
J.   Chem.   Soc.   Chem.   Commun.   (1995) 15, 1523-1524
J.   Org.   Chem.   (1960) 25, 2114-2126
J.   Org.   Chem.   (1979) 44, 659-661.
J.   Org.   Chem.   (1992) 57, 25, 6759-6764
J.   Org.   Chem.   (1993) 58, 5, 1118-1121
Magn.   Reson.   Chem.   (1997) 35, 2, 131-140
Org.   Synth.   (1963) 43, 87
Tetrahedron (1991) 47, 28, 5173-5184
Tetrahedron (1995) 51, 41, 11305-11318
Tetrahedron Lett.   (1981) 22, 18, 1655-1656
Tetrahedron Lett.   (1986) 27, 21, 2335-2336
Tetrahedron Lett.   (1996) 37, 6, 805-808
Z.   Naturforsch.   B (1989) 44, 11, 1475-1478

Method 7:   destructive distillation of alpha-bromopropionic acid with sodium nitrite

K2CO3 + NaNO2 + H2O + a-br-propionic acid  nitroethane 50%yield

Add 20g of the acid to a solution of K2CO3 in the amount of base that causes the solution to be basic to phenolphthalein.   The add 20g of NaNO2--there should be approx.   100ml of solution.   Place in a 250ml rb flask and distill quickly- the first 100ml will come over before the rxn takes place.   Then the nitroethane comes over.   Distill until no more product comes over.(don't distill to dryness)

V.   Auger.   Bull.   Soc.   Chim.   FrancePost no.   3, 23, 333 (1900) by the kolbe method.

Method 8:   oxidation of ethyl amine to nitroethane with dimethyldioxirane

A new synthesis of nitro compounds using dimethyldioxirane(DMDO)
Tetrahedron Letters,Vol.27,No.21,pp 2335-2336,1986

Abstract: Dimethyldioxirane oxidizes primary amines to nitro compounds in a facile, mild, high yield process.

Here we report that aliphatic and aromatic primary amines are rapidly and efficiently oxidized to nitro compounds by dimethyldioxirane, DMDO.   Indeed a survey of some general methods for the preparation of nitro compounds (2) suggests to us that the use of DMDO may be the method of choice.   The conditions used are exceedingly mild and give the nitro compound as a solution in acetone.   Table 1 summarizes our results with some representative amines.

Table 1.   Oxidation of amines with Dimethyldioxirane(DMDO)
Amine Product Yield (%) Product m.p.(C)
Aniline Nitrobenzene 91  
p-Anisidine p-Nitroanisole 94 54
n-Butylamine 1-Nitrobutane 84  
sec-Butylamine 2-Nitrobutane 81  
tert-Butylamine 2-Methyl-2-nitrobutane 90  
1-Aminoadamantane 1-Nitroadamsntane 95 159
Cyclohexylamine Nitrocyclohexane 95  
trans-Azobenzene Azoxybenzene 96 36

In a typical reaction n-butylamine (0.052g; 0.7 mmol) in 5 ml of acetone was treated with 95 ml of DMDO, in acetone solution (ca 0.05M)(4) The solution was kept at room temperature for 30 min. with the exclusion of light.   Analysis of the reaction mixture by capillary GC indicated the presence of l-nitrobutane only.   The oxidations are believed to occur by means of successive oxidations by,1.   In the aniline case the blue color of the nitroso conpound is observed immediately upon adding the solution of DMDO.   In separate experiments we have shown that both phenylhydroxylamine and nitrosobenzene are readily oxidized to nitrobenzene by DMDO.   The blue color of intermediate nitroso compound was observed in all of the amine oxidations.

Dimethyldioxirane is a powerful oxygen atom donor, which oxidizes a variety of substrates 'including hydrocarbons'.   Work is continuing on the oxidation of nitrogen-containing compounds by DMDO.

1.   Chemistry of Dioxiranes.   5.   Paper 4 of this series is J.   Am.   Chem.   Soc., in press (1986).
2.   H.   O.   Larson in The Chemistry of the Nitro and Nitroso Groups, H.   Feuer, Ed., J.   Wiley and Sons.   N.   Y.   1969.
4.   The concentration of,DMDO in acetone was determined by titrating an aliquot with phenyl methyl sulfide.   The synthesis of DMDO has been described (5).
5.   R.   W.   Murray and R.   Jeyaraman, J.   Org.   Chem., (50) 2847 (1985).
Dioxiranes:synthesis and reactions of methyldioxiranes.
J.   Org.   Chem.(1985),50(16),2847-53.

Abstract

The peroxymonosulfate-acetone system produces dimethyldioxirane under conditions permitting distn. of the dioxirane from the synthesis vessel.   The same conditions were used to prep. other methyldioxiranes.   Solns. of dimethyldioxirane prepd. in this manner were used to study its chem. and spectroscopic properties.   The caroate-acetone system was also used to study the chem. of in situ generated dimethyldioxirane.cis- And trans-stilbenes were converted stereospecifically to the corresponding epoxides with dimethyldioxirane in acetone.

Method 9:   isomerization of ethyl nitrite to nitroethane over asbestos catalyst

J.   Chem.   Soc.   109, 701 (1916)
(pass over asbestos in a tube furnace @ 120-130C for best results/best yield)

Method 10:   ethyl bromide, DMSO, NaNO2 and phloroglucinol dihydrate

By Ritter, in Strike's book- TSII.

32g or 26ml EtBr is poured into 250ml of DMSO with 36g NaNO2 and 52g phloroglucinol already present in solution.(Pglucinol is expensive but can be recycled) put on good mag. stirring and stopper the flask.   Stir for two hours in emulsion form, then dump into a 600ml of ice water and extract twice with DCM.   (2x200ml) dry the extracts withMgSO4 or CaCl2 the evap off the DCM.   Distill and collect the fraction from 113-116C--- yields about 20g of nitroethane (80%)(another ref says maybe over 90% consistently)

Other notes:catechol and resorcinol have the same nitrite scavenging abilities as phloroglucinol.   And ethylene glycol can be used as a solvent.   A simple NaOH wash of the final solution (nitroethane removed) will give the sodium salt of your phloroglucinol catalyst.   Acidification of the solution will precip the catalyst for recovery by filtration.

JACS 79, 2507 (1957)
Tetrahedron vol 46, No 21, pp 7443-57 (1990)
Ber.   11, 1332 (1878)
Ber.   12, 417 (1879)
JACS, Vol 78, 1497-1501

Method 11:   3-chloropropionic acid sodium salt, and NaNO2

ClCH2CH2COONa + NaNO2  NO2CH2CH2COONa + NaCl

NO2CH2CH2COONa + H2O heatNO2CH2CH3 + NaHCO3

Modification of Nitromethane synthesis from Organic Synthesis, Vol? Pg 401.

Method 12:   most complicated synth

CH3CH=NOH+ Cl2  CH3CH (Cl)(NO) ( gem-chloronitrosoethane)

Gem-comp + O3  CH3CH (Cl)(NO2)

CH3CH (Cl)(NO2) + NaOH + H2 + Pd/C  nitroethane (50%) + HCl

JOCS, Vol 41, pg 733-735 (1976)

Method 13:   electrochemical oxidation ---- not possible by method below

Ethyl amine is oxidized to methyl nitrile in anhydrous solvent.   In the presence of water it is oxidized to the imine, then acetaldehyde which is further oxidized to acetic acid.

Method 14:   Vapor Phase nitration of propane.

The propane is bubbled through nitric acid heated to 108C and lead into a reactor at 420C.the product is then condensed and fractionated.(26% nitroethane formed)

Industrial and Engineering Chemistry, Vol 28, Mar, 1936.   Pg 339-344.
JOC, Vol 17, pg 906-944.

Method 15:   Vapor Phase nitration of ethane.

Same as propane but at least 80% yields.

Industrial and Engineering Chemistry, Vol 28, Mar, 1936.   Pg 339-344.
JOC, Vol 17, pg 906-944.

Method 16:   Vapor Phase Nitration of Ethanol using Group II oxides or halides as a catalyst (works for methanol and propanol too)

US pat # 4431842

Method 17:   Distillation of alpha-bromopropionic acids with NaNO2 in the presence of Magnesium Sulfate in DMSO

US pat # 4319059

(the alpha-bromo acid can be obtained using propionic acid in the procedure from Org.   Synth.   CV 1, 115.)


Method 18:   Oxidation of alanine with permanganate followed by decarboxylation

Nitroethane via oxidation of alanine?

Theory

MeCH(NH2).   COOH + 3(O) --> MeCH(NO2).   COOH + H2O.

MeCH(NO2).   COOH + NaOH --> MeCH(NO2).   COONa.

MeCH(NO2).   COONa + H2O --> MeCH2(NO2) + NaHCO3.

Procedure

A solution of potassium permanganate (0.3 mol) in water was made by dissolving 47.41 g KMnO4 in 400 mL hot water in a 1 L 3-necked flask fitted with a reflux condenser, a stirbar[note 1], thermometer, and a 100-mL addition funnel.   As the solution cools to room temperature fine crystals of KMnO4 crystallise out of solution[note 2].   A solution of alanine (0.1 mol, 8.91 g) in 65 mL of water was placed in the addition funnel and added dropwise with stirring over a 20 minute period.   The temperature slowly rose.   When the addition was complete, the reaction mixture was heated to 60 over a period of approximately 2 hours.   40 mL of acetone was added [note 3] and then the reaction mixture maintained at 70-85 [the sludge was extremely viscous and the stirbar was of no use] for 2 hours.   0.1 mol sodium hydroxide in 20 mL of water was then added through the addition funnel.

Pause (to be completed).

The flask showed no sign of heating up after addition of the NaOH.   By now the black/brown sludge will not mix (with the stir-bar).   The next step is to heat to 80-100C to decarboxylate any nitro-propionic acid and then to steam distil.

Notes:

1.   An overhead stirrer is essential - the stirbar will get clogged with MnO2.

2.   KMnO4 solubility is 1 in 3.5 parts of hot water and 1 in 14 parts of cold water.

3.   The acetone was added to try to clear the sludge.   I would have added more but I had second thoughts.

Refs:

1.   Synthesis Of Aliphatic And Alicyclic Nitro Compounds; Org.   Syn. p 131-132 [The Oxidation of Amines]

2.   Organic Syntheses, Vol.   52, pp 77-82, 2-Metryl-2-Nitrosopropane and its Dimer, A.   Calder, A.   R.   Forrester and S.   P.   Hepburn.

3.   Vogel's Practical Organic Chemistry, 4th ed.   P 564 'Nitromethane'.

Questions:

1.   Is it safe to heat this mixture to 90C without a stirrer? [the next step to make sure that nitro-propionic acid is decarboxylated]

2.   Should I improvise an overhead stirrer to finish this off?

3.   Nitroethane will steam distill won't it?

4.   Should the permanganate have been buffered?

5.   I think the NaOH should have been in there from the start.   The sodium salt of alanine would have been a better idea?

6a.   Would the reaction benefit from taking place in an organic solvent?

6b.   If so, what solvents are suitable apart from acetone?

I will repeat this - with an overhead stirrer and the addition of sodium salt of alanine rather than alanine followed by NaOH.

Method 19:   Reduction of acetaldehyde oxime and oxidation of the product

Good work! An alternative method to alanine amino oxidation and decarboxylation is the reaction : CH3CHO + NH2OH ==> CH3CH=NOH,
Then carfully reduced to CH3CH2NHOH, and then oxidized as proposed by you above to get CH3CH2NO

NEWEST METHOD

Method 20:   reduction of nitroethene to nitroethane using 2-phenylbenzimidazoline

phenylbenzimidazoline.html

just thought aurelius would add it to the compilation for posterity and preservation.