Org. Synth. 1979, 59, 35
DOI: 10.15227/orgsyn.059.0035
CLEAVAGE OF METHYL ETHERS WITH IODOTRIMETHYLSILANE: CYCLOHEXANOL FROM CYCLOHEXYL METHYL ETHER
Submitted by Michael E. Jung
1 and Mark A. Lyster
12.
Checked by Joan Huguet, H. Shibuya, and S. Masamune.
1. Procedure
A. Iodotrimethylsilane. A 250-ml., two-necked, round-bottomed flask equipped with a magnetic stirring bar, an addition funnel for solids (Note 1), and a reflux condenser bearing a nitrogen inlet is charged with 5.6 g. (0.21 mole) of aluminum powder (Note 2) and 16.2 g. (0.100 mole) of hexamethyldisiloxane (Note 3) and purged with nitrogen. The mixture is stirred and heated with an oil bath at 60° as 50.8 g. (0.200 mole) of iodine is added slowly through the addition funnel over 55 minutes (Note 4). The bath temperature is raised to ca. 140°, and the mixture is heated under reflux for 1.5 hours. The reflux condenser is removed, and the flask is equipped for distillation at atmospheric pressure. The bath temperature is gradually raised from 140° to 210°, and the clear, colorless distillate is collected, yielding 32.6–35.3 g. (82–88%) of iodotrimethylsilane, b.p. 106–109° (Note 5) and (Note 6).
B. Cyclohexanol. A 25-ml., oven-dried, round-bottomed flask is charged with 1.722 g. (0.01524 mole) of cyclohexyl methyl ether (Note 7). The flask is purged with nitrogen and sealed with a rubber septum. With oven-dried syringes, 4 ml. of chloroform (Note 8), 0.5 g. (0.5 ml., 0.006 mole) of pyridine (Note 8) and (Note 9), and 4.8 g. (3.5 ml., 0.024 mole) of freshly prepared iodotrimethylsilane are injected into the flask in the order specified. When the iodotrimethylsilane is added, the solution becomes slightly yellow and a precipitate appears. The mixture is heated without stirring at 60° for 64 hours, after which the reaction is normally complete (Note 10). Anhydrous methanol (2 ml.) is added, the mixture is cooled to room temperature, and the volatile components (Note 11) are removed on a rotary evaporator. Approximately 10 ml. of anhydrous diethyl ether (Note 12) is added, and the resulting suspension is filtered, removing pyridinium hydroiodide. The flask and the filter cake are washed thoroughly with ca. 50 ml. of anhydrous ether. The ether is evaporated, and the residual oil is purified by chromatography on 70 g. of silica gel packed with anhydrous ether in a 3 × 50 cm. glass column. The column is eluted with anhydrous ether, and 5–7 ml. fractions are collected and analyzed by TLC (Note 13). Fractions containing product are combined and evaporated, affording 1.26–1.35 g. (83–89%) of cyclohexanol (Note 14).
2. Notes
1.
The submitters have used both an addition funnel with a worm gear delivery similar to those manufactured by Normag, and an
Erlenmeyer flask attached to the neck of the reaction vessel with a piece of Gooch rubber tubing. Normag addition funnels are available from Lab Glass, Inc., P. O. Box 610, Vineland, New Jersey 08360.
2.
The submitters purchased
aluminum powder from MC and B Manufacturing Chemists. The metal used by the checkers was supplied by J. T. Baker Chemical Company.
3.
Hexamethyldisiloxane is available from Aldrich Chemical Company, Inc. The reagent may also be prepared by the procedure described in the following paragraph. The submitters have used
chlorotrimethylsilane purchased from Aldrich Chemical Company, Inc., and Silar Laboratories, Inc. (10 Alplaus Road, Scotia, New York 12302) either as supplied or after distillation from
calcium hydride. No appreciable difference in yield was noted between preparations using undistilled and distilled reagent.
A 250-ml., three-necked, round-bottomed flask equipped with a magnetic stirring bar, a pressure-equalizing dropping funnel, and a reflux condenser bearing a nitrogen inlet is charged with a solution of 7 g. (0.4 mole) of water in 72.7 g. (76.0 ml., 0.601 mole) of N,N-dimethylaniline and flushed with nitrogen. Stirring is begun, and 62.49 g. (73.00 ml., 0.5754 mole) of chlorotrimethylsilane is added dropwise over 50 minutes. The mixture is heated under reflux in an oil bath at 125–130° for 1 hour. The reflux condenser is replaced by a distilling head, and the product is distilled at atmospheric pressure. The fraction boiling at 98–101° is collected, dried over anhydrous magnesium sulfate, and filtered, affording 43–44 g. (92–94%) of hexamethyldisiloxane as a clear colorless liquid.
4.
In a similar procedure for the preparation of
iodotrimethylsilane,
aluminum,
iodine, and
hexamethyldisiloxane are combined, and the mixture is heated to reflux.
3 When this procedure was attempted by the submitters, violent exothermic reactions occurred at
ca. 50–60°. The slow addition of
iodine to the warm mixture described in the present procedure leads to a controlled, reproducible reaction.
5.
The product is sometimes contaminated with a small amount of
hexamethyldisiloxane. The amount of this contaminant is minimized by using longer reaction times and by careful handling to avoid contact with atmospheric moisture. The product may become discolored during storage, in which case it may be purified by distillation from
copper powder. The
1H NMR spectrum of
iodotrimethylsilane (CDCl
3) exhibits a singlet at δ 0.71 in the presence of
benzene as internal standard.
6.
The submitters obtained
69.4 g. (
87%) of product when the scale was doubled.
7.
Cyclohexyl methyl ether was prepared by the method of Stoocknoff and Benoiton.
4 A
250-ml., two-necked, round-bottomed flask is equipped with a magnetic stirring bar, a rubber septum, and a reflux condenser mounted with a nitrogen inlet. The flask is purged with
nitrogen and charged with
8 g. (0.2 mole) of a 60% dispersion of sodium hydride in mineral oil. The
sodium hydride is washed free of mineral oil with
pentane and suspended in
75 ml. of tetrahydrofuran. After
10 g. (0.10 mole) of cyclohexanol is added by syringe, the mixture is heated under reflux for 22 hours. A
28.4-g. (12.5 ml., 0.200 mole) portion of methyl iodide is injected into the flask, and the resulting mixture is heated under reflux for 18 hours. Water and
chloroform are added to the cooled mixture. The aqueous layer is extracted with three
50-ml. portions of chloroform, the combined
chloroform extracts are dried over anhydrous
magnesium sulfate, and the solvents are evaporated. Distillation of the remaining liquid affords
7.1 g. (
62%) of
cyclohexyl methyl ether, b.p.
133–134°.
8.
Chloroform and
pyridine were dried over Linde type 4A molecular sieves.
9.
Pyridine is added to neutralize small amounts of
hydrogen iodide, often present in
iodotrimethylsilane as a result of hydrolysis by contact with moisture. The amount of by-products, including
cyclohexyl iodide, is reduced by the presence of
pyridine. Hindered
pyridine bases such as
2,6-di-tert-butyl-4-methylpyridine5 have also been used for this purpose, by the submitters. The
pyridine bases do not appear to react with
iodotrimethylsilane.
10.
The progress of the reaction may be conveniently monitored by
1H NMR spectroscopy. After 64 hours the signal at δ 3.25 for the
methoxyl group of
cyclohexyl methyl ether had usually decreased to less than 1% of its original intensity, and peaks for
cyclohexyl iodide could not be discerned. Although the submitters found that the reaction time was decreased by using larger amounts of
iodotrimethylsilane, 5–10% of
cyclohexyl iodide was also produced.
11.
The volatile components are
chloroform,
methanol,
methyl iodide,
methyl trimethylsilyl ether, and
hexamethyldisiloxane.
12.
When the submitters used
technical grade ether, the amount of iodine-containing by-products isolated from the chromatography was increased, and the yield of
cyclohexanol was somewhat lower.
13.
When an insufficient amount of
iodotrimethylsilane was used by the submitters,
cyclohexyl methyl ether remained at the end of the reaction and was eluted from the silica gel column before
cyclohexanol. When present in the crude product,
cyclohexyl iodide was also eluted from the column before
cyclohexanol.
14.
The identity and purity of the product were determined by GC, IR spectroscopy, and
1H NMR spectroscopy by both the submitters and the checkers.
3. Discussion
This procedure describes a convenient method for the preparation of
iodotrimethylsilane and illustrates the use of this reagent for ether cleavage, as in the regeneration of
cyclohexanol from
cyclohexyl methyl ether.
6 Iodotrimethylsilane was first prepared by Whitmore by the reaction of
trimethylphenysilane with
iodine.
7 The reagent has also been generated
in situ by halide exchange between
magnesium iodide and
chlorotrimethylsilane.
8 The present procedure is essentially that of Voronkov and Khudobin,
3 modified by slowly adding
iodine to a mixture of
aluminum and
hexamethyldisiloxane heated at 60° (see
(Note 4)).
The use of methyl ethers as protecting groups for aliphatic alcohols has been hampered by the difficulty of liberating the alcohol from this inert derivative.
9,10 The cleavage of methyl ethers has been previously accomplished with boron reagents such as
boron trichloride,
11,12,13,14,15 boron trifluoride in
acetic anhydride,
16,17 and
diborane or
sodium borohydride in the presence of
iodine.
18,19 Two recent modifications of early methods for cleavage of aliphatic methyl ethers utilize hydrogen iodide generated
in situ10 and
magnesium bromide in
acetic anhydride.
20 Recently described methods for the hydrolysis of methyl ethers include the use of
sodium cyanide in
dimethyl sulfoxide,
21 anhydrous
hydrogen bromide,
22 and
thiotrimethylsilanes.
23The use of
iodotrimethylsilane for this purpose provides an effective alternative to known methods. Thus, the reaction of primary and secondary methyl ethers with
iodotrimethylsilane in
chloroform or
acetonitrile at 25–60° for 2–64 hours affords the corresponding trimethylsilyl ethers in high yield.
6 The alcohols may be liberated from the trimethylsiyl ethers by methanolysis. The mechanism of the ether cleavage is presumed to involve initial formation of a trimethylsilyl oxonium ion which is coverted to the
silyl ether by nucleophilic attack of
iodide at the methyl group.
tert-Butyl, trityl, and benzyl ethers of primary and secondary alcohols are rapidly converted to trimethylsilyl ethers by the action of
iodotrimethylsilane, probably
via heterolysis of silyl oxonium ion intermediates. The cleavage of aryl methyl ethers to aryl trimethylsilyl ethers may also be effected more slowly by reaction with
iodotrimethylsilane at 25–50° in
chloroform or
sulfolane for 12–125 hours,
6 with
iodotrimethylsilane at 100–110° in the absence of solvent,
24,25 and with
iodotrimethylsilane generated
in situ from
iodine and
trimethylphenylsilane at 100°.
25,26Alkyl esters are efficiently dealkylated to trimethylsilyl esters with high concentrations of
iodotrimethylsilane either in
chloroform or
sulfolane at 25–80°
27 or without solvent at 100–110°.
24,26 Hydrolysis of the trimethylsilyl esters serves to release the carboxylic acid. Amines may be recovered from
O-methyl,
O-ethyl, and
O-benzyl carbamates after reaction with
iodotrimethylsilane in
chloroform or
sulfolane at 50–60° and subsequent methanolysis.
28 The conversion of dimethyl, diethyl, and ethylene acetals and ketals to the parent aldehydes and ketones under aprotic conditions has been accomplished with this reagent.
29 The reactions of alcohols (or the corresponding trimethylsilyl ethers) and aldehydes with
iodotrimethylsilane give alkyl iodides
30 and α-iodosilyl ethers,
31 respectively.
Iodomethyl methyl ether is obtained from cleavage of
dimethoxymethane with
iodotrimethylsilane.
32 A review by Schmidt
33 covers the applications of
iodotrimethylsilane listed above along with many more recently published examples.
Appendix
Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)
diborane
trimethylphenysilane
thiotrimethylsilanes
Benzene (71-43-2)
methanol (67-56-1)
ether,
diethyl ether (60-29-7)
acetic anhydride (108-24-7)
acetonitrile (75-05-8)
chloroform (67-66-3)
Cyclohexanol (108-93-0)
sodium cyanide (143-33-9)
hydrogen bromide (10035-10-6)
nitrogen (7727-37-9)
aluminum,
aluminum powder (7429-90-5)
copper powder (7440-50-8)
iodine (7553-56-2)
pyridine (110-86-1)
hydrogen iodide (10034-85-2)
magnesium bromide (7789-48-2)
N,N-dimethylaniline (121-69-7)
Methyl iodide (74-88-4)
Pentane (109-66-0)
Dimethoxymethane (109-87-5)
magnesium sulfate (7487-88-9)
magnesium iodide
iodide (20461-54-5)
boron trifluoride (7637-07-2)
Tetrahydrofuran (109-99-9)
sodium hydride (7646-69-7)
methoxyl (2143-68-2)
boron trichloride (10294-34-5)
dimethyl sulfoxide (67-68-5)
calcium hydride (7789-78-8)
cyclohexyl iodide (626-62-0)
sodium borohydride (16940-66-2)
sulfolane (126-33-0)
CHLOROTRIMETHYLSILANE (75-77-4)
methyl trimethylsilyl ether (1825-61-2)
hexamethyldisiloxane (107-46-0)
Iodotrimethylsilane (16029-98-4)
CYCLOHEXYL METHYL ETHER (931-56-6)
pyridinium hydroiodide
silyl ether (13597-73-4)
trimethylphenylsilane (768-32-1)
Iodomethyl methyl ether (13057-19-7)
2,6-Di-tert-butyl-4-methylpyridine (38222-83-2)
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