Organic Syntheses, CV 6, 501
Submitted by M. N. Sheng and J. G. Zajacek
1.
Checked by William F. Fischer, Jr. and Herbert O. House.
1. Procedure
Caution!
Methyl iodide, in high concentrations for short periods or in low concentrations for long periods, can cause serious toxic effects in the central nervous system. Accordingly, the American Conference of Governmental Industrial Hygienists
2 has set 5 p.p.m., a level which cannot be detected by smell, as the highest average concentration in air to which workers should be exposed for long periods. The preparation and use of
methyl iodide should always be performed in a
well-ventilated fume hood. Since the liquid can be absorbed through the skin, care should be taken to prevent contact.
A solution of
21.3 g. (0.100 mole) of freshly distilled N,N-dimethyldodecylamine (Note
1),
9.6 g. (0.10 mole) of 94% tert-butyl hydroperoxide (Note
2), and
0.050 g. of vanadium oxyacetylacetonate (Note
3) in
27 g. (34 ml.) of tert-butyl alcohol is placed in a
250-ml., round-bottomed flask fitted with a
thermometer, a
reflux condenser, and a heating mantle. The reaction mixture is heated to approximately 65–70°, at which point an exothermic reaction begins. The heating is discontinued until the vigorous exothermic reaction subsides (about 5 minutes); the reaction mixture is then heated at reflux (the reaction mixture boils at 90°) for 25 minutes. After the resulting mixture has been cooled to room temperature,
it is analyzed (Note
4)
to establish the absence of tert-butyl hydroperoxide, then concentrated with a
rotary evaporator (30–35° bath with 30–40 mm. pressure). The crude solid residue is triturated with
50 ml. of cold (0–5°), anhydrous diethyl ether and filtered under conditions which prevent exposure of the residual amine oxide to atmospheric moisture (Note
5). The solid is washed with
50 ml. of cold (0–5°) anhydrous ether and dried under reduced pressure, leaving
12.9–15.5 g. of the crystalline amine oxide, m.p.
131–131.5°. Concentration of the mother liquors and trituration of the residual paste with
25 ml. of cold (0–5°) anhydrous ether separates another
4.9–3.4 g. of the amine oxide, m.p.
130–131°. The total yield of the crystalline amine oxide (Note
6) is
17.4–18.9 g. (
76–83%).
2. Notes
1.
N,N-Dimethyldodecylamine purchased from Eastman Organic Chemicals is approximately 90% pure. This material should be fractionally distilled with a
spinning band column to obtain the pure amine, b.p.
116–117° (4 mm.).
2.
tert-Butyl hydroperoxide purchased from the Lucidol Division, Wallace and Tiernan, Inc., is approximately 92% pure. A portion of the major impurity, water, can be removed by drying the commercial material over anhydrous
magnesium sulfate for 2 days, leaving material that is 94–97% pure.
3.
Vanadium oxyacetylacetonate may be purchased from Alfa Inorganics, Inc., Beverly, Massachusetts.
4. Although consumption of the hydroperoxide is normally complete, the absence of this peroxide in the reaction mixture should be established by testing with moist starchiodide paper or by iodometric titration.
3 The amine oxide content may be determined by titration with standard
hydrochloric acid after any amine present has reacted with
methyl iodide for 1 hour at room temperature.
4 From this volumetric analysis the submitters determined the yield of amine oxide to be
86%. The checkers found that the reaction could be followed by measuring the
1H NMR spectra in
tert-butyl alcohol solution where the
N-methyl signals of the amine (δ 2.03) and the amine oxide (δ 2.98) are readily observed.
5. The amine oxide is exceedingly hygroscopic and must be protected from atmospheric moisture during filtration. The submitters found it convenient to use a
Büchner funnel covered with a large, inverted
rubber stopper. After the mixture of amine oxide and
ether is added to the funnel, the mouth of the funnel is covered with the inverted rubber stopper, and suction is applied. The flat surface of the inverted rubber stopper forms a seal against the mouth of the funnel, preventing the entrance of moist air while the last traces of
ether are removed. The checkers employed a
sintered-glass funnel fitted to maintain a
nitrogen atmosphere above the crystalline product.
6. The hygroscopic amine oxide should be protected from moisture during storage. The checkers found that the initial product could be recrystallized from
toluene under anhydrous conditions to yield the amine oxide as white needles, m.p.
130–131°.
3. Discussion
Aqueous or alcoholic solutions of amine oxides are normally obtained by oxidizing tertiary amines with either
hydrogen peroxide or a
peracid.
5 For example,
N,N-dimethyldodecylamine oxide has been prepared by treating
N,N-dimethyldodecylamine with aqueous
hydrogen peroxide.
6 The procedure illustrated in this preparation permits the oxidation of tertiary amines with
tert-butyl hydroperoxide in organic solvents under relatively anhydrous conditions.
7 In this procedure the reaction time is short, and the method is as convenient as that with aqueous
hydrogen peroxide or a
peracid as the oxidant. Furthermore, isolation of the anhydrous amine oxide is often relatively simple.
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