Organic Syntheses, CV 6, 552
ALKENES
via HOFMANN ELIMINATION: USE OF ION-EXCHANGE RESIN FOR PREPARATION OF QUATERNARY AMMONIUM HYDROXIDES:
DIPHENYLMETHYL VINYL ETHER
Submitted by Carl Kaiser and Joseph Weinstock
1.
Checked by P. Müller and G. Büchi.
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
250-ml., three-necked, round-bottomed flask equipped with a sealed mechanical stirrer, a dropping funnel, and a reflux condenser is charged with
13.3 g. (0.0522 mole) of 2-(diphenylmethoxy)-N,N-dimethylethylamine (Note
1) and
50 ml. of acetone. The solution is stirred, and
8.1 g. (0.057 mole) of methyl iodide in
15 ml. of acetone is added dropwise over 5 minutes (Note
2). After the addition is complete, the mixture is stirred for 30 minutes, then cooled to 0–10° with an
ice bath. The crystalline product is filtered and washed with
15 ml. of acetone and
30 ml. of diethyl ether, yielding
20.0–20.2 g. (
97–98%) of colorless, crystalline methiodide, m.p.
194–196°.
An excess (60 g.,
ca. 0.26 equivalent) of anion exchange resin (OH
− form, (Note
3)) in a
500-ml. Erlenmeyer flask is stirred with
200 ml. of methanol (Note
4) for 5 minutes. The methanolic slurry of resin is transferred to a
6.5 cm. × 25 cm. chromatography column, using
50–100 ml. of methanol to aid in the transfer. The resin column is washed with
750 ml. of methanol, added gradually so as to maintain about a 1–2.5 cm. solvent head above the upper resin level (Note
5). About two-thirds of the resin slurry is poured from the column (using about
100 ml. of methanol to aid the transfer) into a suspension of
19.9 g. (0.0499 mole) of the methiodide in
50 ml. of methanol (Note
6). The mixture is stirred and heated gently on a
water bath, dissolving the crystalline methiodide. The resulting resin suspension is poured onto the column containing the remaining one-third of the resin. Additional
methanol (ca. 50 ml.) is required to facilitate transferral. The column is eluted with about
500 ml. of methanol until the eluent no longer affords an alkaline reaction to pH paper (Note
7). The methanolic eluent is concentrated under reduced pressure (10–25 mm.), and the residual liquid (Note
8) is gradually heated to 100° under the
water-aspirator vacuum. Following completion of thermal decomposition, as evidenced by the end of gas evolution (
ca. 5–10 minutes), the residue is dissolved in
250 ml. of ether (Note
9). The ether solution is washed with
100 ml. of 0.2 N sulfuric acid and 100 ml. of water, dried over
anhydrous magnesium sulfate, and filtered. The filtrate is concentrated, and distillation of the residue gives
8.5–9.0 g. (
81–86%) of
diphenylmethyl vinyl ether as a colorless liquid, b.p.
163–167° (18 mm.),
nD25 1.5716 (Note
10) and (Note
11).
2. Notes
1. The submitters used
2-(diphenylmethoxy)-N,N-dimethylethylamine, b.p. 150–165° (2 mm.),3 obtained from Searle Chemicals, Inc., or from the hydrochloride, m.p. 161–162°, which is available commercially from Gane's Chemical Works, Inc., New York, New York, under the generic name, diphenhydramine.
2. The reaction exotherm is just sufficient to cause moderate reflux.
3. A strongly basic, polystyrene, alkyl quaternary amine (hydroxide form) of medium porosity was employed. Research grade Rexyn 201 (OH) (purchased from Fisher Scientific Company) and Amberlite IRA-400 (purchased from Mallinckrodt Chemical Works) were found to be satisfactory. Chloride-form resins must be converted to the hydroxide form before use, as described below (Note
7).
4. It is necessary to wash the resin with
methanol prior to packing of the column. If this is not done, swelling of the resin on treatment with the solvent may cause explosion of the column.
6. Stirring of the methiodide with the anion exchange resin prior to introduction into the column is necessary, because of the insolubility of this quaternary salt in
methanol. For methanol-soluble methiodides, a solution of the salt may be added directly to the methanol-washed resin column.
7. The recovered resin can be reconverted to the hydroxide form by eluting a column of the material with
aqueous 10% sodium hydroxide until it is free of halide ion (silver nitrate–nitric acid test), then with water until the eluent is no longer alkaline to pH paper.
8. Heating should be carried out in a 1-l. (oversized) flask because decomposition is accompanied by considerable foaming.
10. The product has the following spectral properties; IR (neat) cm.
−1: 1670, 1200, 770, 710;
1H NMR (CDCl
3), δ (multiplicity, approx. coupling constant
J in Hz., number of protons): 3.97 (d of d,
JXY = 2,
JAX = 7, 1H), 4.27 (d of d,
JXY = 2,
JAY = 14, 1H), 5.7 (S, 1H), 6.36 (q,
JAX = 7,
JAY = 14, 1H), 7.2 (S, 10H). The distilled product was about 98% pure by GC analysis on a
60 cm. × 0.6 cm. aluminum column packed with 10% SE-30
silicon rubber on Gas Chrom Z, 100–200 mesh, operated at 180°. The retention time was about 2.0 minutes. Minor amounts of
benzhydrol and
diphenylmethyl methyl ether (retention times 2.5 minutes and 1.8 minutes, respectively) accounted for the remainder of the distillate. The checkers found that GC analysis on a 1.8-m. column packed with 15% SE-30 on GAW, 60–80 mesh at 180°, at an injector temperature of 250° resulted in extensive decomposition. A satisfactory analysis, however, could be performed by lowering the injector temperature to 180°.
3. Discussion
Diphenylmethyl vinyl ether has also been prepared from
benzhydrol and
acetylene under high-pressure conditions.
4 In the described method, an adaptation of the procedure of Weinstock and Boekelheide,
5 improved yields of the alkene are obtained by using more convenient experimental conditions.
The described method for converting a quaternary halide to the corresponding
hydroxide, utilizing an anion-exchange resin, has general application in the Hofmann elimination reaction.
6 It has been used extensively in the submitters' laboratories for the synthesis of a variety of alkenes
7 and for the preparation of a number of
ethyl 1-benzylcyclopropanecarboxylates
via abnormal Hofmann elimination of diethyl [2-(
N,N-dimethylamino)ethyl]benzylmalonates.
8 It offers several notable advantages over more conventional methods for preparing quaternary hydroxides. Formation of quaternary hydroxides from iodides with bases (
e.g.,
silver oxide) that form insoluble iodides has disadvantages due to the expense of the reagent and, in some instances, the oxidizing power of
silver salts in basic solution.
Thallous ethoxide has been used to avoid the oxidation effect; however, it is expensive
9,10,11 and toxic. Quaternary methosulfates may be hydrolyzed to sulfates and converted to the
hydroxide with
barium hydroxide,
12 but this method has not found general application. The described procedure of exchange of
hydroxide ion for halide is suitable for even very sensitive compounds and obviates most of the objectionable features of the precipitation methods.
5,6 In the event that
methanol is undesirable, the conversion may be carried out in water.
5
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