Submitted by Anna Bou, Miquel A. Pericàs, Antoni Riera, and Fèlix Serratosa.
Checked by Terry Singleton, Jae Chan Park, Martin F. Semmelhack, Sean M. Kerwin, and Clayton H. Heathcock.
1. Procedure
A. (1)
Preparation of trans-2,3-dichloro-1,4-dioxane. (See (Note
1).) To a
2-L, three-necked, round-bottomed flask, equipped with two inlet tubes (with sintered-glass diffusers at the end) connected to a
chlorine cylinder, and a
reflux condenser connected to an outlet tube immersed in a
potassium hydroxide solution, are added
1200 g (13.64 mol) of anhydrous dioxane (
free of peroxides!) and
8 g (0.03 mol) of iodine. A stream of
chlorine is passed through the
dioxane/
iodine solution heated at 90°C, and the reaction is monitored by NMR spectroscopy. After 9 hr, the conversion is 50% complete (Note
2); after 33 hr, about 90% complete. At this point, the stream of
chlorine is interrupted.
Reinitiation of the chlorine stream after some hours (next morning, for example) may be dangerous because it was observed in one case the mixture inflamed spontaneously! The reaction mixture is allowed to cool to room temperature,
500 mL of ether is added, and the solution is washed with aqueous
sodium thiosulfate solution. The organic layer is separated, dried over
sodium sulfate, the
ether is evaporated under reduced pressure, and the residue is distilled through a
20-cm Vigreux column, to yield
1200–1300 g of
trans-2,3-dichloro-1,4-dioxane, bp
89°C/16 mm (lit.
1 bp
82.5°C/14 mm; mp
31°C) (Note
3).
(2)
2,3-Di-tert-butoxy-1,4-dioxane. To a
2-L, three-necked, round-bottomed flask, equipped with a
mechanical stirrer, a reflux condenser protected from moisture by a drying tube, and an inlet tube for dry
nitrogen, are added
103.6 g (0.66 mol) of trans-2,3-dichloro-1,4-dioxane,
979.1 g (13.23 mol) of anhydrous tert-butyl alcohol (distilled from CaH
2), and
365.1 g (2.64 mol) of potassium carbonate (ground with a
mortar and pestle and activated at 250°C for 3 hr) (Note
4). The mixture is stirred vigorously and heated under reflux for 24–30 hr, the progress of the reaction being monitored by
1H NMR spectroscopy. Once the singlet at δ 5.95, corresponding to the
methine protons of the starting material, has completely disappeared, the reaction mixture is allowed to cool to room temperature, and poured into
500 mL of ether, and enough water (750–850 mL) is added to dissolve all of the inorganic salts. The organic layer is separated, and the aqueous layer is extracted with two
200-mL portions of ether. The combined
ether extracts are dried over anhydrous
sodium sulfate, filtered, and concentrated under reduced pressure to give
128–147 g of an oily residue (Note
5).
Hexane (250 mL) is added and the solution is allowed to stand in a
refrigerator. The resulting crystals are separated by suction filtration and washed thoroughly with
150–250 mL of hexane. The residue of
3–6 g of crystalline product, mp
106–107°C, which remains insoluble, is identified as
trans-2-tert-butoxy-3-hydroxy-1,4-dioxane (Note
6). The filtrate (which contains approximately a 25 : 75 mixture of
cis and
trans isomers) is evaporated under reduced pressure to one-half its volume and is cooled to 0°C. Massive crystals appear, which are collected by suction filtration. The crystallization process is repeated once more to give
40–60 g of
trans-2,3-di-tert-butoxy-1,4-dioxane, mp
64–65°C. The
hexane solution is evaporated under reduced pressure and the oily residue distilled at
50–57°C/0.25 mm to give
54–84 g of a mixture of
cis- and trans-2,3-di-tert-butoxy-1,4-dioxane (
115–124 g combined;
75–81% yield) (Note
7).
B.
1,2-Di-tert-butoxy-1,2-dichloroethane. To a
250-mL, round-bottomed flask, equipped with a
pressure-equalizing dropping funnel protected from moisture by a drying tube, and a
magnetic stirring bar, are added
43.2 g (0.21 mol) of phosphorus pentachloride and
50 mL of hexane, and the flask is cooled with an
ice–salt bath. While the solution is stirred, a solution of
30 g (0.13 mol) of 2,3-di-tert-butoxy-1,4-dioxane in
100 mL of hexane is added dropwise. After the addition is complete, the cooling bath is removed and the mixture is stirred at room temperature for 90–180 min until no starting material is observed in the NMR spectrum of a sample (Note
8); the reaction mixture is then filtered through a sintered-glass filter to remove excess
phosphorus pentachloride. The resulting
hexane solution (

200 mL), which contains
1,2-di-tert-butoxy-1,2-dichloroethane,
2-chloroethyl dichlorophosphate,
1,2-dichloroethane,
phosphorus oxychloride, and traces of
phosphorus pentachloride, is transferred into a
1-L, three-necked, round-bottomed flask, equipped with a magnetic stirrer, a dry-ice condenser protected from moisture by a
potassium hydroxide tube, and a short inlet tube connected to an
ammonia cylinder. The reaction flask is cooled with a
dry ice–acetone bath and, while the solution is stirred (Note
9), a fast stream of gaseous
ammonia is introduced. A vigorous reaction takes place and a copious white precipitate forms. The stream of gaseous
ammonia is continued for 15–60 min (Note
10). The cooling bath and condenser are removed, the reaction flask is connected to an ordinary aspirator line through a
potassium hydroxide drying trap, and the
ammonia is evaporated under aspirator vacuum with efficient stirring. The ammonia-free solution is filtered through a sintered-glass filter and the precipitate is washed with
hexane. The resulting
hexane solution (400–500 mL), which contains
25–26 g (0.12 mol) of pure 1,2-di-tert-butoxy-1,2-dichloroethane, is suitable for the next operation (yields, calculated from an aliquot, are
95–97%) (Note
11).
C.
(E)-1,2-Di-tert-butoxy-1-chloroethene. The solution prepared above is placed in a
1-L, round-bottomed flask, equipped with a magnetic stirring bar and a
Liebig condenser (protected from moisture by a drying tube) and cooled with an
ice bath;
28.9 g (0.258 mol) of solid potassium tert-butoxide is added in small portions through the condenser over a 30-min period. After addition, the cooling bath is removed and stirring is continued for 90–120 min until no more starting material is detected in the
1H NMR spectrum of a sample; enough ice water is then added to just dissolve all the inorganic salts. The organic layer is separated and the aqueous layer is extracted with
hexane (2 × 100 mL). The combined
hexane extracts are dried over anhydrous
sodium sulfate, filtered, and concentrated at aspirator vacuum. The residue is distilled at
40°C/0.2 mm, with the collection flask at −78°C, to give a center cut of
(E)-1,2-di-tert-butoxy-1-chloroethene (
15.4–17.0 g,
58–63% yield from
2,3-di-tert-butoxy-1,4-dioxane) (Note
12) and (Note
13).
D.
Di-tert-butoxyethyne. In a
2-L, three-necked, round-bottomed flask, equipped with a magnetic stirring bar (Note
14), a dry-ice condenser protected from moisture by a
potassium hydroxide tube, and a
pressure-equalizing dropping funnel,
0.5 mol of sodium amide is prepared in
500 mL of liquid ammonia (Note
15), and
20 g (0.0968 mol) of (E)-1,2-di-tert-butoxy-1-chloroethene dissolved in
150 mL of anhydrous ether is added in a 5-min period with efficient stirring. After the addition, stirring is continued for 80 min. The reaction mixture is diluted with
200 mL of cold pentane (−20 to −30°C), and 400 mL of cold water is added very cautiously. The organic layer is washed with
50 mL of a 0.1 M buffered phosphate solution (NaH
2PO
4/Na
2HPO
4), dried over anhydrous
sodium sulfate (Note
16), filtered, and concentrated at aspirator vacuum without heating to give
10–12 g (
78–86% yield) of
di-tert-butoxyethyne as a pale-yellow oil. The product is sufficiently pure for further reactions (Note
17), but it may be distilled at
30°C/0.05 mm; freezing point 8.5°C.
2. Notes
1. This procedure was reported by J. J. Kucera and D. C. Carpenter.
1,2
2. These data were obtained by the checkers. The submitters report conversion of 76–80% after only 9 hr. It seems likely that the rate of the reaction may be sensitive to the dimensions and mechanical features of the
chlorine introduction system, and/or an induction period. It is easy and important to monitor the process.
3.
trans-2,3-Dichloro-1,4-dioxane has the following spectra: IR (CCl
4) cm
−1: 2990, 2940, 2885, 1455, 1385, 1375, 1337, 1160, 1115, 1032, 900, 875, 670;
1H NMR (CCl
4)
2b δ: 3.40–4.57 (AA'BB', 4 H, CH
2), 5.95 (s, 2 H, ClCHO).
4. The yields of this reaction are very sensitive to the presence of traces of moisture and to the ratio of reagents. If one works without a
nitrogen atmosphere and with
tert-butyl alcohol that has not been previously dried over
calcium hydride, with a 1 : 10 ratio of dichloro derivative/alcohol, the yields drop to
65%.
5.
Caution should be exercised in evaporation of the ether, as the di-tert-butoxy compounds are appreciably volatile at reduced pressure. If a rotary evaporator is used for the concentration, the water bath should be kept at or below room temperature, and the residue should not be pumped after it is clear that the bulk of the ether has been evaporated.
The submitters report ca.
130 g of oily residue at this stage. Treatment of the oily residue with
105 mL of ether leads to partial crystallization. During washing of the crystals in a Büchner filter with more
ether, an almost complete solubilization takes place, but eventually
0.1–0.5 g of cis-2,3,7,10-tetraoxabicyclo[4.4.0]decane remains as an insoluble residue. This compound was prepared for the first time in 1931;
3 the
cis configuration was established only in 1966.
4 It has the following properties: mp
136°C; IR (CCl
4) cm
−1: 2980, 2955, 2930, 2910, 2875, 1460, 1350, 1285, 1260, 1250, 1150, 1140, 1095, 1080, 1025, 910, 870, 780;
1H NMR (CCl
4) δ: 3.30–4.20 (AA'BB', 8 H CH
2), 4.60 (s, 2 H, OCHO).
6. The crystalline trans isomer epimerizes in
chloroform solution to give a nearly 70 : 30 mixture of
cis and
trans isomers. The
trans isomer, mp
106–107°C, shows the following spectroscopic properties: IR (KBr) cm
−1: 3450, 2980, 2935, 2890, 1445, 1390, 1370, 1335, 1280, 1260, 1200, 1135, 1105, 1060, 1045, 1035, 1020, 910, 855, 780;
1H NMR (CCl
4) δ: 1.27 (s, 9 H, CH
3), 3.33–4.13 (ABCD + OH, 4 H + 1 H) 4.57 (br, 2 H, OCHO). Anal. calcd. for C
8H
16O
4: C, 54.53; H, 9.15. Found: C, 54.53; H, 9.29.
7.
trans-2,3-di-tert-butoxy-1,4-dioxane has the following spectra: IR (CCl
4) cm
−1: 2975, 2930, 1390, 1367, 1190, 1145, 1100, 1060, 1040, 857;
1H NMR (CCl
4) δ: 1.19 (s, 18 H, CH
3), 3.05–4.20 (m, AA'BB', 4 H, CH
2), 4.30 (s, 2 H, OCHO).
cis- +
trans-2,3-Di-tert-butoxy-1,4-dioxane have the following additional signals: IR (CCl
4) cm
−1: 1170, 1130, 1120, 1080, 1020, 1000, 960, 879;
1H NMR (CCl
4) δ: 4.43 (s, 2 H, OCHO,
cis).
9. The solution is thick at −78°C. Dilution with additional
hexane may be necessary.
10. The end of the reaction can be easily detected because, when all of the
2-chloroethyl dichlorophosphate has been destroyed, the reaction mixture
does not crackle any more when condensed
ammonia drops on the stirred mixture, or, much more easily, when the reaction mixture becomes basic to pH paper.
11. The crude reaction mixture is, in fact, an approximately 30 : 70 mixture of
dl- and meso-1,2-di-tert-butoxy-1,2-dichloroethane. Although the
1H NMR spectrum at 60 MHz (CCl
4) shows only one singlet at 5.6 ppm, the 200-MHz spectrum (CDCl
3) shows two sharp singlets separated by 1.8 Hz. The pure meso compound could be isolated by crystallization and purified by sublimation at 40°C/0.05 mm; mp
77–78° (dec). The spectra are as follows: IR (CCl
4) cm
−1: 2975, 2925, 1470, 1458, 1390, 1368, 1310, 1250, 1180, 1130, 1025, 850, 650;
1H NMR at 200 MHz (CDCl
3) δ: 1.36 (s, 9 H, CH
3), 5.73 (s, 1 H, OCHCl).
12. In later fractions, small amounts (
0.2–0.5%) of
(Z)-1,2-di-tert-butoxy-1-chloroethane have been detected:
1H NMR (CCl
4) δ: 1.25 (s, 9 H, CH
3), 1.33 (s, 9, H, CH
3), 6.03 (s, 1 H, = CH).
13.
(E)-1,2-Di-tert-butoxy-1-chloroethene has the following properties:
nD25 1.4410–1.4415; UV (cylohexane): 217.7 nm (log ε = 3.7); IR (CCl
4) cm
−1: 2972, 1670, 1470, 1390, 1366, 1290, 1260, 1240, 1180, 1140, 1070, 1025, 935;
1H NMR (CCl
4) δ: 1.26 (s, 9 H, CH
3), 1.33 (s, 9 H, CH
3), 5.91 (s, 1 H, = CH).
14. The
stirring bar must be glass-covered, since
sodium in
ammonia solution attacks Teflon.
15. The method used for the preparation of
sodium amide is a modification of the procedure described by Nieuwland et al.
5 In a
3-L, three-necked, round-bottomed flask, equipped with a magnetic stirring bar (Note
14), a dry-ice condenser protected from moisture by a
potassium hydroxide tube, and an inlet tube connected to the
ammonia cylinder, is condensed 500 mL of liquid
ammonia. A slow stream of dry
oxygen is initiated through the inlet tube and 11.5 g (0.5 mol) of
sodium in small pieces is slowly introduced. The addition of
sodium requires 4–5 hr, since the blue color must be discharged before each new addition of
sodium. In this way, a completely white suspension of
sodium amide is obtained, which allows the formation of crude
di-tert-butoxyethyne, free from any
iron impurities.
17. Eventually, if a more concentrated solution of
(E)-1,2-di-tert-butoxy-1-chloroethene in
ether is used, the formation of
1,2,3-tri-tert-butoxy-3-cyano-1-propene [
1H NMR (CCl
4) δ: 6.05 (s, 1 H), 4.98 (s, 1 H), 1.28 (br, 27 H)] and
1,2,3-tri-tert-butoxy-1-cyano-1-propene [
1H NMR (CCl
4) δ: 4.03 (s, 2 H), 1.28 (b, 27 H)] is observed. The by-products may be eliminated by column chromatography on neutral
alumina (40 g, 100–125 mesh, activity 1), using a column refrigerated at 0°C and protected from the light, and eluting with
pentane under
nitrogen pressure. From the first 750 mL of eluant,
9–12 g of pure
di-tert-butoxyethyne is obtained.
18.
Di-tert-butoxyethyne has the following properties:
nD25 1.4365; IR (CCl
4) cm
−1: 2972, 2922, 1470, 1450, 1390, 1367, 1301, 1263, 1245, 1150, 825;
1H NMR (CCl
4) δ: 1.31 (s, CH
3).
3. Discussion
Appendix
Compounds Referenced (Chemical Abstracts Registry Number)
dl- and meso-1,2-di-tert-butoxy-1,2-dichloroethane
Propane, 2,2'-j[1,2-ethynediylbis(oxy)]bis[2-methyl-
ACETAL (105-57-7)
potassium carbonate (584-08-7)
acetylene (74-86-2)
ammonia (7664-41-7)
Benzene (71-43-2)
ether (60-29-7)
hydrogen (1333-74-0)
glyoxal (107-22-2)
phosphorus pentachloride (10026-13-8)
chloroform (67-66-3)
iron (7439-89-6)
sodium sulfate (7757-82-6)
oxygen (7782-44-7)
sodium thiosulfate (7772-98-7)
1,2-dichloroethane (107-06-2)
nitrogen (7727-37-9)
iodine (7553-56-2)
methine (7782-42-5)
Phosphorus Oxychloride (21295-50-1)
chlorine (7782-50-5)
potassium hydroxide (1310-58-3)
sodium (13966-32-0)
Pentane (109-66-0)
dioxane (5703-46-8)
methylene (2465-56-7)
isobutene (9003-27-4)
sodium amide (7782-92-5)
hexane (110-54-3)
tert-butyl alcohol (75-65-0)
calcium hydride (7789-78-8)
phosphate
trans-2,3-Dichloro-1,4-dioxane (3883-43-0)
2-chloroethyl dichlorophosphate (1455-05-6)
1,2-dichloro-1,2-dimethoxyethane
potassium tert-butoxide (865-47-4)
Di-tert-butoxyethyne (66478-63-5)
trans-2-tert-butoxy-3-hydroxy-1,4-dioxane
trans-2,3-di-tert-butoxy-1,4-dioxane
2,3-Di-tert-butoxy-1,4-dioxane,
cis- and trans-2,3-di-tert-butoxy-1,4-dioxane (68470-79-1)
1,2-Di-tert-butoxy-1,2-dichloroethane (68470-81-5)
(E)-1,2-Di-tert-butoxy-1-chloroethene (70525-93-8)
cis-2,3,7,10-tetraoxabicyclo[4.4.0]decane
(Z)-1,2-di-tert-butoxy-1-chloroethane
1,2,3-tri-tert-butoxy-3-cyano-1-propene
1,2,3-tri-tert-butoxy-1-cyano-1-propene
tert-butoxyketene
2,3,4-tri-tert-butoxycyclobutenone
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