Organic Syntheses, CV 7, 517
Submitted by Tom Livinghouse
1
Checked by Tod Holler, Kevin J. Carlin, and G. Büchi.
1. Procedure
Caution!
Trimethylsilyl cyanide is very toxic. All reactions in this sequence should be carried out in a hood.
A.
Trimethylsilyl cyanide. A
1-L, round-bottomed flask equipped with a magnetic stirrer, nitrogen inlet, and a 60-mL addition funnel is charged with
5.0 g (0.624 mol) of lithium hydride (Note
1) and
500 mL of anhydrous tetrahydrofuran (Note
2).
The stirred suspension is cooled in an ice bath and
42.6 g of acetone cyanohydrin (45.7 mL, 0.501 mol) (Note
3) is added dropwise over 15 min. After the addition is complete, the ice bath is removed and the mixture stirred for 2 hr at room temperature (Note
4).
The magnetic stirring bar is removed and the solvent evaporated as completely as possible on a
rotary evaporator.
The white
lithium cyanide is then dried in vacuo for 3 hr (Note
5) and (Note
6).
The
lithium cyanide is freed from the sides of the flask and broken up with a spatula (Note
7).
A
250-mL round-bottomed flask equipped with an ice bath, magnetic stirrer, thermometer, and nitrogen inlet is charged with
54.32 g (63.46 ml, 0.500 mol) of trimethylchlorosilane (Note
8) and
100 mL of bis[2-(2-methoxyethoxy)ethyl] ether (Note
9).
The
lithium cyanide is added to this stirred solution over 15 min through Gooch tubing (Note
10).
After the addition is complete, the ice bath is removed and the milky suspension stirred overnight at room temperature.
The Gooch tubing and the
thermometer are then removed from the reaction flask and a stillhead equipped for downward vacuum distillation is attached.
A
100-mL, round-bottomed flask immersed halfway in an
acetone-dry ice slush bath (Note
11) is employed as the receiver.
The volatile compounds are distilled under a pressure of 50 mm (bp 25–55°C) by heating the contents of the pot using an
oil bath (Note
12).
The distillate is carefully redistilled through a
well-insulated 15-cm column packed with glass helices under an inert atmosphere.
A 25–40 mL forerun (bp 66–113°C), consisting primarily of
tetrahydrofuran and
hexamethyldisiloxane, is first collected.
The second fraction, containing
29–41 g (
59–82%) of
trimethylsilyl cyanide, bp
114–117°C,
nD25 1.3902 (Note
13), then distills.
A purity of ca. 97% was established by GC analysis (Note
14) and (Note
15); the product is suitable for synthetic use without further purification.
B.
Cyanosilylation of p-benzoquinone. A
100-mL, round-bottomed flask equipped with a magnetic stirrer, West condenser, and a nitrogen inlet is charged with
6.30 g (58.2 mmol) of p-benzoquinone (Note
16),
10 mL of dry carbon tetrachloride, and
8 mL (63.03 mmol) of trimethylsilyl cyanide.
The stirred suspension is heated to a gentle reflux by means of a heat gun to dissolve all the
p-benzoquinone.
It is then allowed to cool slowly until the crystallization of the
p-benzoquinone starts (Note
17), at which time 5 mg of the 1 : 1 complex between
potassium cyanide and 18-crown-6 (Note
18) is added through the top of the condenser.
An immediate vigorous reflux sets in and continues for 1–2 min (Note
19).
The stirred reaction mixture is permitted to cool slowly to room temperature, whereupon the condenser is removed and
3 g of Florisil (Note
20) is added.
After stirring for an additional 15 min,
10 mL of dry carbon tetrachloride is added.
The suspension is then filtered and the filtercake leached with three
5-mL portions of carbon tetrachloride.
The solvent is evaporated from the filtrate as completely as possible on a
rotary evaporator, at which point crystallization of the residue usually begins (Note
21).
The last traces of solvent and
trimethylsilyl cyanide are then removed in vacuo over 20 hr at 50 μ to afford
12.0–12.2 g of crude product.
The trimethylsilyl cyanohydrin is recrystallized by dissolving the crude material in
25 mL of hot hexane and allowing the resulting solution to cool slowly to room temperature (Note
22).
After collection by filtration the product is rinsed with two
5-mL portions of hexane and airdried to yield
7.54–9.77 g (
63%–81%) of white to buff-colored needles, mp
65–67°C (Note
23) and (Note
24).
2. Notes
1. Commercial
lithium hydride (Alfa Products, Morton Thiokol, Inc.) was used.
2. Commercial
tetrahydrofuran was distilled from
sodium benzophenone ketyl immediately before use.
3. Commercial
acetone cyanohydrin (Aldrich Chemical Company, Inc.) was used without further purification.
4. A vigorous evolution of
hydrogen gas occurs during the addition of the
acetone cyanohydrin.
Hydrogen evolution virtually ceases after stirring at room temperature for 2 hr.
5. It is essential to exclude atmospheric moisture as much as possible during this operation.
7. This operation must be performed rapidly to avoid water absorption by the hygroscopic
lithium cyanide.
10. The internal temperature is maintained at or below 35°C during this operation by periodic cooling with an ice bath.
11.
Trimethylsilyl cyanide solidifies in the receiver during the course of the distillation.
It is absolutely necessary that the receiver be immersed no more than halfway in the slush bath.
Further immersion may cause the product to solidify in the end of the condenser.
This necessitates cessation of the distillation to unclog the apparatus.
12. The temperature of the oil bath is raised from 25 to 110°C over 45 min and then maintained at the upper temperature until no more product distills.
13. The product exhibits the following properties:
1H NMR (CCl
4 with CHCl
3 internal standard) δ: 0.4 [s, Si(CH
3)
3]; IR (neat) cm
−1: 2200 (-CN).
14. The GC analysis was performed on an
8-ft column packed with 5% OV-17 on Anachrome ABS.
16.
Commercial p-benzoquinone (Matheson, Coleman, and Bell, Inc.) was recrystallized from
95% ethanol before use.
17. The initiation of crystallization indicates the optimum reaction temperature for the catalyzed cyanosilylation of
p-benzoquinone.
The use of higher temperatures results in excessive darkening of the product and a decrease in yield.
18. The 1 : 1 complex is conveniently prepared by dissolving
0.652 g (10 mmol) of pulverized potassium cyanide and
2.640 g (10 mmol) of commercial 18-crown-6 (Aldrich Chemical Company, Inc.) in
45 mL of anhydrous methanol by swirling and warming.
The
methanol is then evaporated at a
rotary evaporator and the white complex dried in vacuo over night.
19.
Caution! Extreme care must be taken during the addition of the catalyst.
The addition of too much catalyst or the use of higher reaction temperatures may result in the reaction mixture boiling over.
20.
Florisil obtained from Matheson, Coleman, and Bell, Inc. was used.
21. Crystallization of the residue may also be induced by the addition of a seed crystal or scratching with
glass rod.
22. In some instances addition of a seed crystal during cooling is necessary.
24. An analytically pure sample, mp
67–67.5°C, may be obtained by a second recrystallization from
cyclohexane:
1H NMR (CCl
4) δ: 0.30 (s, 9, CH
3), 6.30 (d, 1,
J = 10, C=CH), 6.83 (d, 1,
J = 10, C=CH); IR (CCl
4) cm
−1: 1678 (C=O), 1252, 845 (Si-CH
3).
3. Discussion
Trimethylsilyl cyanide is a useful reagent for the preparation of β-amino alcohols,
6 α-amino nitriles,
2 and α-trimethylsiloxyacrylonitriles
3 from the corresponding ketones, imines, and ketenes.
The reagent adds rapidly to the carbonyl of aldehydes at 25°C,
6 and the resulting adducts have proved useful precursors for the preparation of carbonyl anion synthons.
4 Enones give exclusively the products derived from 1,2-addition.
6
Table I illustrates the cyanosilylation of several representative ketones and aldehydes.
This preparation is referenced from:
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