Organic Syntheses, Vol. 76, 189
Checked by Shino Manabe and Kenji Koga.
1. Procedure
2. Notes
1. The drying tube contains
Drierite as the drying agent.
2.
Squaric acid can be obtained from the Aldrich Chemical Company, Inc.
3.
Methanol (99.9%, 0.02% H2O) was used as received from Fisher Scientific Company.
4.
Trimethyl orthoformate (98%) was used as received from the Aldrich Chemical Company, Inc. It is important to use the 98% solution rather than the available 99.8% solution in order to avoid unwanted excess of this reagent (Note
5).
6. The temperature of the refluxing solution is approximately 56°C.
7. The initial heterogeneous mixture become homogeneous after approximately 2.5 hr under reflux conditions.
8. The purpose of this operation is to remove the by-product,
methyl formate (bp
34°C), by short path distillation.
9. The temperature of the solution after distillation is approximately 63°C.
10. All volatile components are removed under reduced pressure using a rotary evaporator; the crude product is subsequently placed under an oil pump for 2 hr.
12. The
silica gel (230-400 mesh) was purchased from East Merck Science.
13. The precipitate is very hard and difficult to remove from the flask. By redissolving in
methylene chloride/diethyl ether the product is obtained as a fluffy white solid.
14.
Anhydrous ether (99.9%, 0.002% H2O) was used as received from Fisher Scientific Company.
15. The product shows no contaminant at the baseline by TLC analysis and has the following spectral properties:
1H NMR (300 MHz, CDCl
3) δ: 4.37 (s);
13C NMR (75 MHz, CDCl
3) δ: 61.0, 184.5, 189.2.
17. For a recent review on the synthetic utility of
squaric acid and related cyclobutenones see Moore.
3
18. The synthesis of
dimethyl squarate as outlined here is a general method that can be employed for the synthesis of a variety of other alkyl squarates.
4
20.
Vinyllithium was purchased from Organometallics Inc. as a 2.35 M solution in
tetrahydrofuran and used as such. Best results are obtained when a new bottle is used, and yields are very dependent upon the quality of the reagent.
21.
Vinyllithium can also be generated in situ by the dropwise addition of 90 mL of a 1.02 N solution of
methyllithium in ether (91.48 mmol) to a solution of 4.5 mL (24.63 mmol) of
tetravinyltin (Aldrich Chemical Company, Inc.) in
tetrahydrofuran (60 mL) at 0°C. The solution is stirred at 0°C for 30 min and used directly. The checkers obtained a 93% yield of product using
vinyllithium thus prepared.
24. The water bath should not exceed 35°C because of possible decomposition.
25. The vinylcyclobutenedione
2 will elute from the column as the second yellow band.
26. Prolonged exposure to air will result in decomposition of the vinylcyclobutenedione.
27. If a solid is not initially formed the oil will solidify upon standing under vacuum.
28. Spectral properties are as follows: IR (CHCl
3) cm
−1: 2690, 1790, 1770, 1750, 1620, 1590, 1580, 1460, 1410, 1370, 1350, 1050;
1H NMR (300 MHz, CDCl
3) δ: 4.48 (s, 3 H), 5.87 (dd, 1 H, J = 10.5, 1.9), 6.50 (dd, 1 H, J = 17.6, 1.8), 6.65 (dd, 1 H, J = 17.6, 10.5);
13C NMR (500 MHz, CDCl
3) δ: 61.4, 122.1, 128.9, 173.4, 192.6, 192.8, 194.6; MS (EI), m/e (rel intensity) 138 (12), 110 (30), 95 (75), 82 (22), 67 (39), 58 (14), 53 (100). Exact mass calcd for C
7H
6O
3: 138.0317, found 138.0335.
29.
1-Hexyne (97% purity) was purchased from Lancaster Chemical Company, Inc., and used as such.
30.
Butyllithium was purchased from Aldrich Chemical Company, Inc., as a 1.6 M solution in hexane and titrated with
diphenylacetic acid to indicate a concentration of 1.1 M at the time of use.
32. The progress of the reaction can be monitored by TLC (
ethyl acetate:hexanes = 1:5).
33. The spectral properties are as follows: IR (CCl
4) cm
−1: 2959, 2783, 1655, 1448, 1321, 1215, 1143, 999, 935, 885;
1H NMR (300 MHz, CDCl
3) δ: 0.93 (t, 3 H, J = 7.0), 1.43 (m, 4 H), 2.42 (t, 2 H, J = 6.7), 4.08 (s, 3 H), 5.63 (dd, 1 H, J = 12.0, 2.4), 6.26 (dd, 1 H, J = 17.7, 2.1), 6.41 (s, 1 H), 6.70 (dd, 1 H, J = 17.7, 12.0);
13C NMR (300 MHz, CDCl
3) δ: 13.7, 22.3, 28.7, 29.9, 60.8, 124.7, 125.1, 125.4, 130.6, 149.5, 154.4, 183.8, 187.2; MS (EI) m/e (rel int) 220 (19), 177 (44), 160 (65), 135 (45), 91 (43), 79 (43), 67 (54), 53 (100); exact mass calcd for C
13H
16O
3: 220.1099, found 220.1108.
All toxic materials were disposed of in accordance with "Prudent Practices in the Laboratory"; National Academy Press; Washington, DC, 1995.
3. Discussion
Two other syntheses of
dimethyl squarate have been reported.
2 One such method involves the formation of the disilver salt of
squaric acid followed by treatment with
methyl iodide. This process, unfortunately, is laborious as well as costly. The other synthesis involves the reaction of
squaric acid with
diazomethane. This reaction not only gives a lower yield, but is inherently unsuited for large scale preparations. The synthesis presented here provides a convenient and inexpensive route to the preparation of
dimethyl squarate, and is also suitable for large scale synthesis.
4 One should take precautions when synthesizing or using dialkyl squarates, particularly
dimethyl squarate, since they are known to cause severe contact dermatitis.
5 Thus, all procedures should be carried out in the hood and protective clothing and gloves should be worn.
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