Organic Syntheses, CV 6, 869
Submitted by D. Seebach
1 and A. K. Beck.
Checked by A. Brossi, N. W. Gilman, and G. Walsh.
1. Procedure
A.
2-Tetradecyl-sym-trithiane. A
1-l., round-bottomed, side-armed flask containing a
magnetic stirring bar is charged with
25.0 g. (0.180 mole) of finely ground, pure, sym-trithiane (Note
1). The flask is equipped with a
three-way stopcock and a
rubber septum on the side arm. The air in the flask is replaced with dry
nitrogen (Note
2).
Tetrahydrofuran (Note 3) (350 ml.) is added by syringe, and the resulting slurry is stirred vigorously in a
cooling bath at −30° (Note
4). After the addition of
0.190 mole of n-butyllithium (1.5–2.5 molar in
n-hexane) (Note
5), the mixture is stirred for 1.5–2.5 hours, keeping the bath temperature between −25° and −15°. After this period of time the
trithiane is dissolved (Note
6), and dry ice is added (no excess!) to the bath until the temperature is about −70°. To this cooled solution is rapidly added
50.0 g. (49.5 ml., 0.180 mole) of 1-bromotetradecane (myristyl bromide) (Note
7) by syringe, and the resulting mixture is stirred overnight, during which time the bath temperature rises to 0–25° and a heavy, colorless precipitate separates. Stirring is continued for 1 hour at room temperature before the mixture is poured into a
2-l. separatory funnel containing 800 ml. of water and
500 ml. of carbon tetrachloride. After shaking, the layers are separated and the aqueous layer is shaken with two additional
500-ml. portions of carbon tetrachloride. Some undissolved
trithiane is filtered from the combined organic layers, which are washed with water and dried over anhydrous
potassium carbonate. The solvent is removed by evaporation, yielding
54–59 g. of crude, solid
2-tetradecyl-sym-trithiane, after drying under reduced pressure (Note
8).
B.
Pentadecanal dimethyl acetal. The crude material obtained from Part A is placed in a
2-l., three-necked flask fitted with an overhead
stirrer, a
reflux condenser with
drying tube, and a stopper.
Methanol (1 l., reagent grade) is added, the stirrer is started, and
40 g. (0.18 mole) of mercury(II) oxide and
100 g. (0.368 mole) of mercury(II) chloride are introduced. The mixture is heated under reflux for 4.5 hours and filtered through a
Büchner funnel after cooling. The residue is washed with
300 ml. of pentane (Note
9), and the combined organic solutions are poured into 1 l. of water. The layers are separated, and the lower aqueous layer is shaken with two
500-ml. portions of pentane. The combined organic layers are quickly washed with
10% ammonium acetate solution (Note
10) and water and dried over
sodium sulfate. The
pentane is evaporated under reduced pressure, giving
30.0–32.5 g. of the crude
acetal as a mobile, slightly yellow oil.
C.
n-Pentadecanal. The crude acetal from Part B is dissolved in
600 ml. of tetrahydrofuran, and 150 ml. of water containing
2 g. of p-toluenesulfonic acid monohydrate is added. The resulting pale mixture is heated at reflux for 1 hour and cooled. The hydrolysate is poured into 600 ml. of water and extracted with three
300-ml. portions of pentane (Note
9). The colorless
pentane extracts are combined, washed three times with saturated
sodium hydrogen carbonate solution and once with water, and dried over
sodium sulfate. Evaporation of the solvent furnishes an oil which upon distillation under reduced pressure (Note
11) yields
18.7–22.5 g. of
n-pentadecanal, b.p.
103–106° (0.2 mm.). The overall yield from
1-bromotetradecane is
47–55%. The product solidifies eventually and should be kept under an inert atmosphere in the refrigerator.
2. Notes
1. It is essential that the
sym-trithiane be of good purity. Commercial
sym-trithiane can be purified by extraction from a thimble in a hot extractor using
300 ml. of toluene for
30 g. of trithiane. After cooling the extract to 0°,
sym-trithiane is recovered by filtration and recrystallized from
toluene. In one run the checkers used
sym-trithiane as obtained from Eastman Organic Chemicals and observed a 10% decrease in yield of
n-pentadecanal.
2. This is done by evaporating and filling with dry
nitrogen three times; during the reaction a pressure of about 50 mm. is maintained against the atmosphere using a
mercury bubbler.
4. A
2-l. Dewar cylinder was used.
5. The checkers used
120 ml. of 1.6 M n-butyllithium in hexane, obtained from Foote Mineral Company.
6. If the
trithiane, apart from a few crystals, does not dissolve entirely, the workup procedure is complicated. The crude
tetradecyltrithiane must then be purified (by dissolving in
500 ml. of carbon tetrachloride at 30°, filtering, and precipitating with
1.5 l. of methanol) before conversion to the acetal.
7. A commercial product (Aldrich Chemical Company, Inc., or Matheson, Coleman and Bell) proved satisfactory without further purification. The purity should be checked by refractive index and/or GC.
9. Low-boiling
ligroin can be used as well.
10. A white precipitate is formed during the first and second washing.
11. A short-path distillation apparatus with a cold finger, but no condenser, should be used since the product may crystallize. The distillation is carried out under
nitrogen or
argon (balloon at capillary).
3. Discussion
The procedure described here provides a convenient route to aldehydes, with
trithiane serving as an inexpensive, “masked” carbonyl group.
2,3,4 The reaction is limited, however, to the use of primary alkyl halides, aldehydes, and ketones for elaboration of the carbon chain through attack on the metallated
trithiane. Examples of aldehydes synthesized by this method are given in Table I.
TABLE I
ALDEHYDES FROM 2-LITHIO-1,3,5-TRITHIANE AND ALKYL HALIDES
|
|
|
|
Aldehyde |
Halide |
2-Alkyl-1,3,5-Trithiane %a,b,c |
Aldehyde Dimethyl Acetal Yield, Yield, %a,b |
Product |
Yield, %a,e,f |
|
1-Bromopentane |
96 |
66d |
Hexanal |
43 |
(S)-(+)-1-Iodo-2-methylbutane |
98 |
67d,g |
(S)-(−)-3-Methylpentanal |
41 |
1-Bromoheptane |
100 |
60d |
Octanal |
45 |
1-Bromodecane |
100 |
99c |
Undecanal |
65 |
1-Bromohexadecane |
100 |
60c |
Heptadecanal |
32 |
Benzyl Bromide |
100 |
32d |
Phenylacetaldehyde |
20 |
|
|
b Reaction conducted on 100 mmoles scale.
|
|
|
e Reaction conducted on 5–10 mmoles scale.
|
f Yield of distilled or recrystallized product.
|
g (+)-Iodide with optical purity of 89% gave acetal with αD + 7.6° (neat, l = 100 mm.).
|
The
S-acetal is converted to the
O-acetal in anhydrous
methanol because hydrolysis of monosubstituted trithianes in aqueous
methanol furnishes a mixture of the free aldehyde and its
O-acetal derivative. It is advantageous to store aldehydes as the
O-acetal derivatives since free aldehydes are susceptible to polymerization and oxidation.
This preparation is referenced from:
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