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Org. Synth. 1972, 52, 77
DOI: 10.15227/orgsyn.052.0077
2-METHYL-2-NITROSOPROPANE AND ITS DIMER
[Propane, 2-methyl 2-nitroso-]
Submitted by A. Calder, A. R. Forrester1, and S. P. Hepburn.
Checked by David S. Crumrine and Herbert O. House.
1. Procedure
A. 2-Methyl-2-nitropropane. To a well-stirred suspension of 650 g. (4.11 moles) of potassium permanganate in 3 l. of water, contained in a 5-l., three-necked flask fitted with a reflux condenser, a mechanical stirrer, a thermometer, and a 250-ml. dropping funnel, is added, dropwise and with stirring over a 10- minute period, 100 g. (1.37 moles) of tert-butylamine (Note 1). When the addition is complete, the reaction mixture is heated to 55° over a period of approximately 2 hours, and maintained at 55° with continuous stirring for 3 hours. The dropping funnel and reflux condenser are replaced with a stopper and a still head fitted for steam distillation, and the product is steam distilled from the reaction mixture (Note 2). The liquid product is separated from the denser water layer, diluted with 250 ml. of diethyl ether, and washed successively with two 50-ml. portions of 2 M hydrochloric acid and 50 ml. of water. After the ethereal solution has been dried over anhydrous magnesium sulfate, the solution is fractionally distilled at atmospheric pressure, removing the ether. The residual crude product (Note 3) totals 106–128 g. and is sufficiently pure for use in the next step. In a typical run, distillation of 124 g. of the crude product affords 110 g. (78%) of the pure 2-methyl-2-nitropropane as a colorless liquid, b.p. 127–128°, n25D 1.3992, which slowly solidifies on standing to a waxy solid, m.p. 25–26° (Note 4).
B. N-tert-Butylhydroxylamine. Caution! Since hydrogen may be liberated during the reduction with aluminum amalgam, the reaction should be conducted in a hood. Also, the aluminum amalgam may be pyrophoric. Consequently, it should be used immediately and not allowed to become dry.
Aluminum foil (30 g. or 1.1 g.-atoms, thickness 0.002–0.003 cm.) is cut into strips 5 × 25 cm., and each strip is rolled into a cylinder about 1 cm. in diameter. Each of the aluminum foil cylinders is amalgamated by immersing it in a solution of 8.0 g. (0.030 mole) of mercury(II) chloride in 400 ml. of water for 15 seconds. Each amalgamated cylinder is then rinsed successively in ethanol and ether, and added to a mixture of 1.5 l. of ether and 15 ml. of water (Note 5) contained in a 3-l., three-necked flask fitted with a dropping funnel, a mechanical stirrer, and two efficient reflux condensers in series. The reaction mixture is stirred vigorously, and 60 g. (0.58 mole) of 2-methyl-2-nitropropane is added dropwise at a rate such that the ether refluxes briskly. The reaction usually exhibits a 5- to 7-minute induction period, after which a vigorous reaction occurs and cooling with an ice bath is necessary. After addition of the nitro compound is complete, the reaction mixture is stirred for an additional 30 minutes. The stirrer is then stopped and the gelatinous precipitate is allowed to settle. The colorless reaction solution is decanted through a glass wool plug into a 2-l. separatory funnel and washed with two 250-ml. portions of 2 M aqueous sodium hydroxide (Note 6). The precipitate in the reaction flask is washed with two 500-ml. portions of ether, and these washings are combined and washed with the aqueous sodium hydroxide solution (Note 6). The combined ethereal solutions are dried over anhydrous sodium sulfate and concentrated with a rotary evaporator. The residual crystalline solid is dried under reduced pressure (10–15 mm.) at room temperature, leaving 33.7–38.7 g. (65–75%) of the crude hydroxylamine product, m.p. 59–60°, which is sufficiently pure for use in the next step. The crude product may be recrystallized from pentane, yielding the pure N-tert-butylhydroxylamine as white plates, m.p. 64–65° (Note 7).
C. 2-Methyl-2-nitrosopropane. A solution of sodium hypobromite is prepared by adding, dropwise and with stirring over a 5-minute period, 57.5 g. (18.5 ml., 0.360 mole) of bromine to a solution of 36.0 g. (0.900 mole) of sodium hydroxide in 225 ml. of water. The resulting yellow solution, contained in a 1-l., three-necked flask fitted with a mechanical stirrer, a thermometer, and an acetone–dry ice cooling bath, is cooled to −20°. A suspension of 26.7 g. (0.300 mole) of N-tert-butylhydroxylamine in 50 ml. of water is added to the reaction flask, with continuous stirring, as rapidly as possible without allowing the temperature of the reaction mixture to exceed 0°. The reaction solution is again cooled to −20° before the cooling bath is removed and the mixture is stirred for 4 hours while the reaction mixture warms to room temperature. The solid product, the nitroso dimer which has separated, is collected on a sintered glass funnel, pulverized, and washed with 1 l. of water (Note 8). The residual solid is dried at room temperature under reduced pressure (10–15 mm.), leaving 19.6–22.2 g. (75–85%) of the 2-methyl-2-nitrosopropane dimer, m.p. 80–81° (Note 9). The product is sufficiently pure to be stored (Note 10) for use as a free radical trapping reagent.
2. Notes
1. tert-Butylamine, purchased from Aldrich Chemical Company, Inc., may be used without purification.
2. Approximately 1 l. of distillate needs to be collected to remove the product from the reaction mixture.
3. The principal contaminant is residual ether.
4. The purified product exhibits IR bands (CCl4) at 1545 cm.−1 (broad) and 1355 cm.−1 (NO2) with a UV maximum (95% C2H5OH) at 279 nm (ε 24) and a 1H NMR (CCl4) singlet at δ 1.58 [(CH3)3C]. The mass spectrum has the following abundant fragment peaks: m/e (rel. int.), 57 (100), 41 (74), 39 (45), and 29 (57).
5. Since water is one of the reactants in this reduction, it is necessary that at least a stoichiometric quantity of water is present.
6. Since the hydroxylamine product is readily oxidized by air to the blue nitroso compound, these manipulations should be performed rapidly to minimize exposure of the product to atmospheric oxygen. Any nitroso compound formed at this stage will co-distil with the ether and is difficult to recover.
7. The product has IR absorption (CCl4) at 3600 cm.−1 and 3250 (broad) cm.−1 (OH and NH) with 1H NMR (CCl4) singlets at δ 1.09 [9H, C(CH3)] and 5.86 (2H, NH and OH). The mass spectrum has the following abundant peaks: m/e (rel. int.), 89 (M+, 11), 74 (96), 58 (41), 57 (100), 56 (52), 42 (41), 41 (74), 39 (34), 29 (54), and 28 (39).
8. Thorough washing to remove the last traces of alkali is essential, or the nitroso dimer will decompose to volatile products on standing.
9. When the colorless nitroso dimer is dissolved in various solvents, it partially dissociates, forming a blue solution which contains an equilibrium mixture of monomer and dimer. In C6D6 and CCl4, the 1H NMR spectrum of the initial solutions of dimer changes rapidly and equilibrium is established within 20–30 minutes. From 1H NMR measurements at about 40° the equilibrium mixtures in CCl4 and C6D6 contain 80–81% of the monomer;2 the 1H NMR singlets attributable to tert-butyl groups are observed at δ 1.24 (monomer) and 1.57 (dimer) in CCl4 and at δ 0.97 (monomer) and 1.49 (dimer) in C6D6. The IR spectrum of the equilibrated mixture (CCl4) exhibits absorption at 1565 cm.−1 attributable to the N=O group of the monomer; this peak is not observed in the IR spectrum (KBr) of the dimer. The mass spectrum of the product exhibits the following abundant fragment peaks: m/e (rel. int.), 72 (10), 57 (100), 56 (23), 55 (21), 42 (22), 41 (97), 39 (55), 30 (49), 29 (74), and 28 (53). A water solution of the dimer initially is colorless and exhibits a UV maximum at 287 nm (ε 8000). On standing, the solution slowly turns blue. A solution of the dimer in C2H5OH, after standing for 20–30 minutes, exhibits maxima at 292 nm (ε 682 dimer) and 686 nm (ε 14.5 monomer).
10. The submitters report that if the product is stored at 0° in the dark, it may be kept indefinitely.
3. Discussion
The oxidation of tert-butylamine to 2-methyl-2-nitropropane is an example of a procedure previously illustrated in Org. Synth.3 N-tert-Butylhydroxylamine has previously been prepared by acid-catalyzed hydrolysis of 2-tert-butyl-3-phenyloxazirane4 and by oxidation of tert-butylamine.5 The procedure described here is based on a method mentioned briefly by Smith and co-workers.6 2-Methyl-2-nitrosopropane has been prepared directly by oxidation of tert-butylamine,2,5 but is usually obtained by oxidation of the hydroxylamine.7 2-Methyl-2-nitrosopropane has also been prepared by electrolytic reduction8 or by zinc dust reduction9 of 2-methyl-2-nitropropane.
2-Methyl-2-nitrosopropane is an excellent scavenger of free radicals and is now widely used in "spin trapping" experiments10,11 (although it has certain disadvantages).12 In this technique, a reactive radical is trapped by the nitroso compound and identified by analysis of the e.s.r. spectrum of the so-formed stable nitroxide radical. The perdeuterated derivative of 2-methyl-2-nitrosopropane has also been recommended for this purpose.13 tert-Butylhydroxylamine, an intermediate in the present procedure, may also be used to synthesize tert-butylphenylnitrone which has been used as a "spin-trapping" reagent.11 The reaction of 2-methyl-2-nitrosopropane with aryl Grignard reagents has been used to prepare N-aryl-N-tert-butylhydroxylamines.14

References and Notes
  1. Department of Chemistry, University of Aberdeen, AB9 2UE, Old Aberdeen, Scotland.
  2. J. C. Stowell, J. Org. Chem., 36, 3055 (1971).
  3. N. Kornblum and W. J. Jones, Org. Synth., Coll. Vol. 5, 845 (1973).
  4. W. D. Emmons, J. Am. Chem. Soc., 79, 5739 (1957).
  5. E. Bamberger and R. Seligman, Ber. Dtsch. Chem. Ges., 36, 685 (1903); R. J. Holman and M. J. Perkins, J. Chem. Soc. C, 2195 (1970).
  6. P. A. S. Smith, H. R. Alul, and R. L. Baumgarten, J. Amer. Chem. Soc., 86, 1139 (1964).
  7. W. D. Emmons, J. Am. Chem. Soc., 79, 6522 (1957).
  8. P. E. Iversen and H. Lund, Tetrahedron Lett., 4027 (1967).
  9. F. D. Greene and J. F. Pazos, J. Org. Chem., 34, 2269 (1969).
  10. M. J. Perkins, P. Ward, and A. Horsfield, J. Chem. Soc. B, 395 (1970); C. Lagercrantz and S. Forshult, Acta Chem. Scand., 23, 708 (1969).
  11. O. H. Griffith and A. S. Waggoner, Acct. Chem. Res., 2, 17 (1969); E. G. Janzen, Acct. Chem. Res., 2, 279 (1969); 4, 31 (1971); M. J. Perkins, Chem. Soc., Spec. Publ., No. 24, 97 (1970).
  12. A. R. Forrester and S. P. Hepburn, J. Chem. Soc. C, 701 (1971).
  13. R. J. Holman and M. J. Perkins, J. Chem. Soc. C, 2324 (1971).
  14. A. R. Forrester and S. P. Hepburn, J. Chem. Soc. C, 1277 (1970) and other papers in this series.

Appendix
Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)

ethanol (64-17-5)

hydrochloric acid (7647-01-0)

ether,
diethyl ether (60-29-7)

hydrogen (1333-74-0)

sodium hydroxide (1310-73-2)

potassium permanganate (7722-64-7)

bromine (7726-95-6)

sodium sulfate (7757-82-6)

oxygen (7782-44-7)

aluminum (7429-90-5)

zinc (7440-66-6)

mercury(II) chloride (7487-94-7)

Pentane (109-66-0)

sodium hypobromite

magnesium sulfate (7487-88-9)

2-Methyl-2-nitropropane (594-70-7)

2-Methyl-2-nitrosopropane,
Propane, 2-methyl 2-nitroso- (6841-96-9)

N-tert-Butylhydroxylamine,
tert-Butylhydroxylamine (16649-50-6)

2-tert-Butyl-3-phenyloxazirane (7731-34-2)

tert-Butylamine (75-64-9)

tert-butylphenylnitrone