Checked by Scott R. Breining and Robert K. Boeckman, Jr..
1. Procedure
B.
1-Bromo-3-(2-methoxyethoxy)propane (2). A
flame-dried, three-necked, 1000-mL flask that is equipped for magnetic stirring, and has a dry addition funnel and a thermometer, is placed under an inert atmosphere and charged with
209 mL (250 g, 0.209 mol) of a 1.0 M solution of borane-tetrahydrofuran complex (Note
2). The resulting solution is cooled to −10°C using a
dry ice/ethylene glycol bath and
3-(2-methoxyethoxy)propene (1, 60 g, 0.52 mol) is added dropwise over

1 hr keeping the internal temperature of the reaction mixture at or below 0°C.
Methanol (1.5 mL) is added to destroy any excess
borane, and the reaction mixture is stirred an additional 1 hr below 10°C.
After the reaction mixture is recooled to −15°C (internal temperature),
35 mL (107.8 g, 0.67 mol) of bromine (Br2) is added dropwise over 1 hr, keeping the reaction temperature between −10° and 0°C. The mixture is stirred a further 1.5 hr at 0°C then recooled to −15°C. While cooling is maintained,
210 mL of a 4 M solution of sodium methoxide (0.84 mol) in methanol (freshly prepared from sodium metal) is added dropwise over 1.5 hr, keeping the reaction temperature between −15° and 0°C. The resulting orange brown solution and white precipitate are slowly warmed to room temperature and stirred overnight (16 hr).
Hexane (100 mL) is added to the reaction mixture causing more white precipitate to form. The mixture is filtered by suction, and the collected solids are washed with two
50-mL portions of hexane. The combined filtrate and washings are partitioned with
200 mL of a mixture (1:3 v/v) of saturated potassium carbonate solution and water (Note
8). The aqueous phase is extracted with three
200-mL portions of hexane. The combined organic phases are partitioned with
100 mL of saturated sodium chloride, dried thoroughly over
anhydrous sodium sulfate and concentrated under reduced pressure to afford
65–75 g of crude product. A small amount of additional crude material can be isolated by continuously extracting the combined aqueous layers with
hexane for 3 hr.
Distillation of the crude product through a
6-in. Vigreux column at 0.6 mm into a
dry ice/acetone-cooled receiver affords
55–70 g of material bp
>40°C/0.6 mm that is

83% pure (as judged by gas chromatography, (Note
6)). To obtain material of greater purity (94%) suitable for further transformation, a second distillation through a
6-in. Vigreux column packed with glass beads is required to afford
53–57 g (
52–56%) of the bromide as a colorless liquid, bp
55–65°C/0.6 mm (Note
9).
C.
Tetra[3-(2-methoxyethoxy)propyl]stannane (3). A
500-mL, three-necked flask is fitted with a thermometer and a dried addition funnel, charged with
9.1 g (0.375 mol) of magnesium metal turnings (Note
2) and heated with a flame or
heat gun while purging with
argon. After the flask is cooled,
50 mL of dry tetrahydrofuran (THF) and a crystal of
iodine are added, and the addition funnel is charged with
40 mL (52 g, 0.264 mol) of 1-bromo-3-(2-methoxyethoxy)propane (
2<.htm/A>, (Note 10)). Approximately 2 mL of the bromide is added to the reaction mixture, and the internal temperature of the mixture is monitored. When the temperature rises slightly (

3°C) and the
iodine color is discharged indicating that formation of the Grignard reagent has begun, the reaction mixture is immediately cooled to −15°C in a dry ice/ethylene glycol bath,
100 mL of dry THF (Note
10) is added to the addition funnel, and
150 mL of dry THF (Note
10) is directly added to the reaction mixture. The bromide solution is added dropwise over 2 hr while keeping the reaction temperature between −15° and 5°C (Note
11).
The concentration of the Grignard reagent solution is determined by titration. An
oven-dried, 10-mL flask with septum is charged with
1 mg of phenanthroline and 3.0 mL of the reaction mixture.
2-Methylpropanol is added until the red-purple color is dissipated and a yellow endpoint is reached. The yield of Grignard reagent is 0.184 mol (70%).
A
dry, 1000-mL flask is placed under a
nitrogen atmosphere, charged with
4.9 mL (0.042 mol) of tin(IV) chloride (SnCl4, (Note 1)), and cooled to −78°C in a
dry ice/acetone bath with swirling. After the SnCl
4 solidifies on the walls of the flask, the flask is equipped for magnetic stirring. The previously prepared Grignard solution is added to the SnCl
4 as a slow stream via cannula and the reaction mixture is allowed to warm to room temperature with stirring overnight (20 hr). After the solution is stirred at room temperature for

20 hr, the addition funnel is replaced by a
reflux condenser, and the reaction mixture is heated at reflux for 4 hr by means of a heating mantle (Note
12). After the solution is cooled, the solvent is removed under reduced pressure, 300 mL of water is added, and the resulting mixture (a heavy precipitate results) is continuously extracted with
750 mL of hexane for 12–24 hr. The
hexane solution is dried over
magnesium sulfate (MgSO4), and the volatile material is removed under reduced pressure, to afford
23.6–24 g (
96–97% based on SnCl
4) of the tetraalkylstannane that is not homogeneous as judged by NMR integration. Pure stannane suitable for further transformation is obtained by removal of a low boiling impurity (bp 90–100°C/0.6 mm) under high vacuum to afford
21–23 g of purified stannane. Stannane (bp
210–215°C at 0.005 mm) of even higher purity can be obtained by short-path distillation with some loss due to decomposition (Note
13).
2. Notes
1.
Potassium hydroxide was A.C.S. reagent grade obtained from J. T. Baker Chemical Company and used as received.
2.
2-Methoxyethanol was research grade obtained from Aldrich Chemical Company, Inc., and used as received.
3. The reaction is exothermic, and temperature control is required for control of the reaction. Good agitation is essential to avoid occlusion of unreacted starting materials in the sticky precipitate.
4. Substantial amounts (grams) of CaH
2 may be required (care should be taken on addition because of foaming) if predrying with Na
2SO
4 is incomplete.
6. Analysis was performed on a
25-m fused silica capillary column with DX-3 (polymethylsiloxane) stationary phase and a temperature program from 50°C-150°C.
7. The spectra are as follows:
1H NMR (300 MHz, CDCl
3) δ: 3.39 (s, 3 H), 3.59–3.61 (m, 4 H), 4.03 (dt, 2 H, J = 5.7, 1.6), 5.18 (dq, 1 H, J = 10.3, 1.6), 5.28 (dq, 1 H, J = 17.2, 1.6),5.92 (ddt, 1 H, J
1 = 17.2, J
2 = 10.3, J
1 = 5.7 );
13C NMR (75.43 MHz, CDCl
3) δ: 58.64, 69.03, 71.70, 71.95, 116.62, 134.55.
8. Three phases may result. If three phases are present, add the minimum amount of additional water that affords two phases. Addition of large amounts of water should be avoided because of the significant water solubility of the product.
9. The spectra as as follows:
1H NMR (300 MHz, CDCl
3) δ: 2.18 (quintet, 2 H), 3.42 (s, 3 H), 3.54–3.68 (m, 8 H);
13C NMR (75.4 MHz, CDCl
3) δ: 30.57, 32.71, 58.99, 68.61, 70.23, 71.81. The checkers noted a larger variability in yield (
38–56%).
11. Inadequate temperature control leads to the formation of by-products resulting from elimination.
12. Magnetic stirring is difficult because of the formation of a sticky precipitate. A very vigorous reaction ensues upon heating the mixture to reflux if inadequate agitation occurs during addition of the Grignard reagent or if the SnCl
4 is allowed to solidify in a pool in the bottom of the flask.
13. The spectra are as follows:
1H NMR (300 MHz, CDCl
3) δ: 0.77 (m, 8 H, apparent t within a doublet), 1.78 (m, 8 H), 3.39 (s, 12 H), 3.39 (t, 8 H), 3.55 (AA'BB' m, 16 H); in
D2O, d
4-TSP ref. δ: 0.89 (m, 8 H), 1.84 (m, 8 H), 3.64 (m, 16 H), 3.53 (t, 8 H), 3.40 (s, 12 H);
13C NMR (75.4 MHz, CDCl
3) δ: 4.44, 26.69, 59.00, 69.95, 71.90, 74.82 (apparent
13C-
119Sn
1J = 322,
2J = 19,
3J = 66);
119Sn NMR 111.86 MHz (200 mg/mL) CDCl
3, Me
4Sn ref. δ: −3.8 ppm (inverse gated decoupled).
14. Discharge of the yellow color is instantaneous until >13 mL of the
bromine solution is added. A persistent yellow color was not observed until 1 equiv of
bromine had been added.
15. No unreacted tetraalkylstannane is observed when a full equivalent of
bromine is employed.
16. The bromotrialkylstannane is stable to storage under
argon in the freezer, and can be converted to the tin hydride as needed.
17. The spectra are as follows:
1H NMR (300 MHz, C
6D
6) δ: 1.38 (br t, 6 H), 1.95 (br quintet, 6 H), 3.14 (s, 9 H), 3.25 (m, 12 H), 3.35 (m, 6 H);
13C NMR (75.4 MHz, CDCl
3) δ: 15.06 ppm (apparent
13C-
119Sn
1J = 413,
3J = 64), 26.04, 58.90, 70.06, 71.71, 73.44;
119Sn NMR 111.86 MHz (200 mg/mL), Me
4Sn ref. δ: +60.0 ppm (inverse gated decoupled). CI MS with NH
3 gave peaks at m/e 471 (base peak) and m/e 433 with the isotopic distribution expected for Sn and Br.
18. The spectra are as follows:
1H NMR (300 MHz, C
6D
6) δ: 0.94 (td, 6 H, J = 8, J
HSnCH = 1.8), 1.85 (quintet, 6 H, J
avg = 7), 3.15 (s, 9 H), 3.36 (t, 6 H, J = 6.4), 3.40–3.52 (m, AA'BB', 12 H),5.17 (br septet, 1 H, J<2);
13C NMR (75.4 MHz, C
6D
6) δ: 4.87, 27.54, 58.28, 70.00, 71.97, 74.03, (apparent
13C-
119Sn
1J = 354,
2J = 22,
3J = 52, apparent
13C-
117Sn
1J = 336,
2J = 22,
3J = 52);
119Sn NMR 111.86 MHz (200 mg/mL), C
6D
6, Me
4Sn standard δ −82.4 ppm (d of septets,
1J
Sn-H = 1612,
2J
Sn-H = 55); IR (film on NaCl) cm
−1: 3500 weak, 2970–2930 strongest absorption, ν
Sn-H1 1810, 1452, 1358, 1300, 1285, 1245, 1200, 1140-1100 broad, 1040, 985, 925, 885, 850, 715, 685.
Anal: Calcd for C18H40SnO6, MW 471.19: C, 45.88; H, 8.56; Sn, 25.19. Found: C, 45.74, 45.76; H, 8.71, 8.36; Sn, 25.08, 25.17.
All toxic materials were disposed of in accordance with "Prudent Practices in the Laboratory"; National Academy Press; Washington, DC, 1995.
3. Discussion
Tributyltin hydride is a common reagent, used extensively in free radical chemistry.
2 However, it is soluble only in typical organic solvents. The tin hydride reagent prepared here
3 can be used in free radical chemistry in many solvents. It is soluble in organic media, but also has sufficient water solubility (30 mM at room temperature, more on warming) to be useful in aqueous reactions. This reagent is not only of interest for use with water-soluble biomolecules but there is also increasing interest in the special effects of water as solvent on organic reactions.
4,5,6 In addition, the reaction product of this reagent is the corresponding
tin oxide species that can be easily recovered and recycled, and that is sometimes more easily removed from organic products than is the corresponding product from
tributyltin hydride. Most notably, this reagent is non-volatile and odorless.
This procedure illustrates the bromopropylation of an alcohol by allylation and then hydroboration/bromination,
7 a clean, selective procedure compared with other approaches via 3-substituted propyl bromide derivatives. Conversion to the tetraalkyl tin, then brominative cleavage, is the standard sequence for preparation of trialkyl tin derivatives.
8 The standard
lithium aluminum hydride (LiAlH4) reduction of the tin bromide was not usable here because of contamination of the product by LiAlH
4 by-products that were not easily separated, and the polymethylhydrosiloxane reduction method
9 was not successful. However, use of NaBH
4 in
1,2-dimethoxyethane was effective and convenient.
10
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