Checked by H. A. Davis, K. Abe, and S. Masamune.
1. Procedure
A.
Diethyl 2,2-diethoxyethylphosphonate (Note
1). A
2-l., three-necked, round-bottomed flask fitted with a
magnetic stirrer,
dropping funnel, and
nitrogen inlet is charged with
410 g. (2.08 moles) of bromoacetaldehyde diethyl acetal (Note
2), and a gentle stream of
nitrogen is then passed continuously through the system. To the stirred solution is added dropwise
316 g. (1.90 moles) of triethyl phosphite (Note
3) over a period of 30 minutes, at 110–120°. The mixture is then stirred for 3 hours at 160°. The
ethyl bromide evolved is trapped with a
condenser and a
receiver cooled in an
ice bath. The low-boiling material (below 100°) is distilled under reduced pressure (22 mm.). The residual oil is fractionated under reduced pressure, and the fraction boiling at
101–103° (0.8 mm.) is collected, yielding
338 g. (
70%) (Note
4).
B.
Diethyl formylmethylphosphonate (Note
5). A mixture of
192 g. (0.755 mole) of diethyl 2,2-diethoxyethylphosphonate and
670 ml. of 2% hydrochloric acid is refluxed for 10 minutes under a
nitrogen atmosphere. To the cooled (20–30°) mixture is added
240 g. of sodium chloride (Note
6). The resulting mixture is extracted with three,
500-ml. portions of dichloromethane. The combined organic extracts are washed successively with
40 ml. of 5% aqueous sodium hydrogen carbonate solution (Note
7) and 300 ml. of saturated aqueous salt solution, dried over anhydrous
sodium sulfate, and distilled under reduced pressure (35 mm.) at water bath temperatures (60–70°). The resulting residue, weighing approximately 125 g., is fractionated under reduced pressure, and the fraction boiling at
100–103° (0.8 mm.) is collected, yielding
104 g. (
76%) (Note
8) and (Note
9).
C.
Diethyl 2-(cyclohexylamino)vinylphosphonate. A
1-l., two-necked, round-bottomed flask fitted with a magnetic stirrer, dropping funnel, and nitrogen inlet is charged with
90.0 g. (0.500 mole) of diethyl formylmethylphosphonate and
400 ml. of dry methanol. Under a
nitrogen atmosphere,
49.6 g. (0.501 mole) of cyclohexylamine (Note
10) is added in portions to the stirred solution, over a period of 5 minutes. During the addition the temperature is maintained at 0–5° with an ice bath. The mixture is stirred for an additional 10 minutes at room temperature, and then the
methanol is distilled from the mixture under reduced pressure (10–35 mm.) at water bath temperatures (25–30°). The residue is dissolved in
300 ml. of dry diethyl ether (Note
11), dried over anhydrous
potassium carbonate (70 g.) (Note
12), and evaporated to dryness. The residual oil is fractionated under reduced pressure in the presence of
300 mg. of anhydrous potassium carbonate (Note
13), and the fraction boiling at
126–141° (0.08 mm.) is collected, giving
89 g. (
68%) (Note
14). The fraction above is crystallized from dry
pentane (Note
15), yielding
79 g. (
60%) of
diethyl 2-(cyclohexylamino)vinylphosphonate, m.p.
58–61° (Note
16).
2. Notes
1. This procedure is essentially the same as that described by Dawson and Burger.
3
4. The reported
3 boiling point is
128–130° (2 mm.). The checkers found the product to be pure by GC (UCW-98 at 150°). The
1H NMR spectrum had the following characteristic peaks (CDCl
3): δ 1.22, 1.34 (2t,
J = 7Hz., 12H, 4C
H3), 2.17 (d of d,
J = 19 and 6Hz., 2H, C
H2CH), 3.6 [2q,
J = 7Hz., 4H, CH(OC
H2CH
3)
2], 4.1 [2q,
J = 7Hz., 4H, (CH
3C
H2O)
2PO], 4.90 [d of t,
J = 6 and

6Hz., 1H, CH
2C
H(OC
2H
5)
2].
5. This procedure is essentially the same as that described by Dawson and Burger.
3
6. It is necessary to saturate the aqueous layer with
sodium chloride in order to extract the product effectively.
7. The checkers found that it was necessary to neutralize any excess acid to prevent polymerization of the product during the distillation.
8. There is no report of the boiling point of the product in the literature.
3 The product has an IR absorption (CCl
4 solution) at 1732 cm.
−1 (aldehyde C=O).
9. The checkers found that the product contained a 5–6% contamination of starting material [GC (UCW-98, 120°) and
1H NMR]. The
1H NMR spectrum (CDCl
3): δ 1.35 (t,
J = 7 Hz., 6H, 2C
H3), 3.11 [d of d,
J = 22 and 3.5 Hz., 2h, P(O)C
H2CH], 4.2 [2q,
J = 7 Hz., 4H, (CH
3C
H2O)
2PO], 9.70 (d of t,
J = 3 and 1 Hz., 1H, C
HO).
11. Dry
ether was used to minimize the water content of the solution.
14. The yields were
65–75% in several runs. The distilled oil was sufficiently pure for further use.
15.
Reagent grade pentane passed through
Merck anhydrous neutral alumina was used. Crystallization was carried out at 0° using
50 ml. of dry pentane. Filtration of the crystals was carried out under dry
nitrogen. The submitters succeeded in crystallizing
diethyl 2-(cyclohexylamino)vinylphosphonate only after the publication of its preparation.
4 The crystalline product is stable for several months, if stored at 0° under anhydrous conditions.
16. The checkers were not able to obtain the product in crystalline form. The
1H NMR spectrum (CDCl
3): δ 1,3 (t,
J = 7 Hz., C
H3CH
2O), 1.0–2.1 (m, cyclohexyl
H), 4.0 (quintet,
J = 7 Hz., 2 C
H3C
H2O), 4.3–5.0 (broad, N
H), 5.9–7.7 (m, -CH=CH-). The number of olefinic protons was estimated to be 1.7–1.8 by comparison of the area in the region δ 5.9–7.7 with the total area in the spectrum. Although this value is slightly low, it was found that the sample was sufficiently pure to carry out further transformations. The IR spectrum has the following absorptions (neat): 3300 (N-H str.), 1620, 1210, 1058, 1035, and 955 cm.
−1.
3. Discussion
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