Organic Process Research & Development
Article
then air-dried on the filter under suction, and then to constant
weight in an oven at 40 °C, leaving behind the crude bisketal 10
(3793g, 80%) as pale beige solid, which was used in the next
step without further processing.
the resin. The methanol solution mixture was then evaporated
to dryness using a rotary evaporator (45 °C at 45 mmHg)
leaving behind the crude diester 3 (863 g) as a dark brown
solid. Purification by sublimation (100−120 °C/0.01 mmHg),
followed by recrystallization from acetonitrile furnished the
diester 3 (560 g, 30%), as a colorless solid, mp 164.5 °C (lit.
161−162 °C).47 1H NMR δ: 3.7, s, 6H 4.24, s, 6H, ring
protons. 13C NMR δ: 47.03, 51.55, 55.77, 171.89.
endo-2,4-Dibromodicyclopentadiene-1,8-dione (6). A 100
L glass reactor was charged with 98% H2SO4 (12.5 L) at
ambient temperature. The crude bisketal 10 (3793 kg, 9.3 mol)
was then added in portions over a period of 1 h, with stirring
(150 rpm), while maintaining the temperature of the reaction
mixture at 25 °C. The resulting reaction mixture was then
stirred for 30 h at 25 °C; the progress of the reaction was
ASSOCIATED CONTENT
* Supporting Information
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S
1
monitored by H NMR for the complete absence of ketal-
Analytical data of crude and purified products S2-7 UV
spectrum of dione 6 S8 DSC and TGA charts of 2 and 3 S9-10
Drawings of the photolysis rig and flow cell. This material is
proton resonances. Once judged complete, the reaction mixture
was then run out into separate vessel containing a mixture of ice
and water (40 L) while being stirred. The resultant slurry was
filtered under vacuum. The solid collected was then washed
successively with water (15 L), then air-dried on the filter under
suction, and then to constant weight in an oven at 40 °C,
affording the dione 6 (2773g, 93%) as a beige colored solid,
which was used in the next step without further processing.
Dimethyl 1,4-Cubanedicarboxylate (3). The crude dione 6
(2.7 kg, 8.5 mol) was dissolved in methanol (47 L), water (8.5
L), and sulfuric acid (66 mL, 15 mol %) in a 100 L glass reactor
(holding vessel) under an atmosphere of nitrogen, at 10 °C.
This solution was then pumped continuously, using a
diaphragm pump, at a rate of 4 L/min, through a 6.4 L
photolysis cell while being irradiated with a 2 kw medium
pressure Hg lamp, and then returned to the holding vessel, with
the average residence time per pass being 1.6 min. During this
time the temperature of the air cooled photolysis cell was
maintained between 40 and 45 °C, whereas the temperature of
the holding vessel was maintained at 25 °C. Irradiation was
continued for a total of 173 h, after which time the olefinic
AUTHOR INFORMATION
Corresponding Author
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Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank (the late) Mr. Chris Hallam for technical support,
and acknowledge the efforts of Dr. Wendy Tian (DSC and
TGA) and Mr. Anton Launikonis (UV).
REFERENCES
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(1) Alvarez, S.; Echeverría, J. J. Phys. Org. Chem. 2010, 23, 1080−
1087.
́
(2) Mlinaric-Majerski, K.; Dodziuk, H.; Gribanova, T. N.; Minkin, V.
I.; Minyaev, R. M.; Suzuki, T.; Takeda, T.; Kawai, H.; Fujiwara, K.;
Lee, V. Y.; Sekiguchi, A. In Strained Hydrocarbons; Dodziuk, H., Ed.;
Wiley-VCH Verlag GmbH & Co. KGaA, 2009; pp 33−102.
(3) Hopf, H.; Liebman, J. F.; Perks, H. M. In PATAI’S Chemistry of
Functional Groups; John Wiley & Sons, Ltd, 2009.
1
resonances of 6 were no longer visible by H NMR.
The crude photolyzed solution was then concentrated to
dryness using a rotary evaporator (45 °C at 60 mm Hg), leaving
behind the cage dione 7 (ca. 3 kg), as a gummy dark-brown
solid.
The crude cage dione 7 was then dissolved in water (23 L) and
transferred into a 100 L glass reactor, stirred (150 rpm), and
heated under reflux for 3 h, to ensure hydrolysis of any
dimethyl ketals of 7 that may have formed during photolysis,
and then cooled to ambient temperature. Solid sodium
hydroxide (6.7 kg) was then added in portions to the stirred
solution, and the resulting alkali mixture heated under reflux for
3 h, then cooled to ambient temperature.
32% aqueous HCl (15 L) was then added slowly over several
hours, with stirring (150 rpm), to the precooled (0 °C)
aqueous alkali reaction mixture; during this addition the
temperature was maintained at or below 5 °C. The acidified
mixture (pH 1−2) was left stirring overnight at room
temperature and then filtered under vacuum. The collected
solid was then dried on the filter under suction for several
hours. The solid filter cake was washed with ice-cold water (2 ×
5 L) and dried in the oven at 45 °C, until constant weight,
leaving behind the crude diacid 2 (1287 g) as a dark brown
solid.
A dry 100 L glass reactor was charged with the crude diacid 2
(1287 g), dry methanol (36 L), and Dowex ion-exchange resin
50WX8−100 (176 g) that was prewashed with 1 L of methanol.
This mixture was then stirred (150 rpm), and heated under
reflux for 18 h under an atmosphere of nitrogen. The mixture
was then cooled to room temperature and filtered to remove
(4) Yildirim, T.; Gehring, P. M.; Neumann, D. A.; Eaton, P. E.;
Emrick, T. Carbon 1998, 36, 809−815.
(5) Fleischer, E. B. J. Am. Chem. Soc. 1964, 86, 3889−3890.
(6) Chickos, J. S. J. Chem. Eng. Data 2010, 55, 1558−1563.
(7) Eaton, P. E. Angew. Chem., Int. Ed. Engl. 1992, 31, 1421−1436.
(8) Roux, M. V.; Martín-Valcarcel, G.; Notario, R.; Kini, S.; Chickos,
J. S.; Liebman, J. F. J. Chem. Eng. Data 2011, 56, 1220−1228.
́ ́
(9) Roux, M. V.; Davalos, J. Z.; Jimenez, P.; Notario, R.; Castano, O.;
̃
Chickos, J. S.; Hanshaw, W.; Zhao, H.; Rath, N.; Liebman, J. F.;
Farivar, B. S.; Bashir-Hashemi, A. J. Org. Chem. 2005, 70, 5461−5470.
(10) Li, Z.; Anderson, S. L. J. Phys. Chem. A 2003, 107, 1162−1174.
(11) Martin, H.-D.; Urbanek, T.; Pfohler, P.; Walsh, R. J. Chem. Soc.,
̈
Chem. Commun. 1985, 964−965.
(12) Maslov, M. M.; Lobanov, D. A.; Podlivaev, A. I.; Openov, L. A.
Phys. Solid State 2009, 51, 645−648.
(13) Bashir-Hashemi, A.; Chickos, J. S.; Hanshaw, W.; Zhao, H.;
Farivar, B. S.; Liebman, J. F. Thermochim. Acta 2004, 424, 91−97.
(14) White, M. A.; Wasylishen, R. E.; Eaton, P. E.; Xiong, Y.;
Pramod, K.; Nodari, N. J. Phys. Chem. 1992, 96, 421−425.
(15) Eaton, P. E.; Cole, T. W. J. Am. Chem. Soc. 1964, 86, 3157−
3158.
(16) Paquette, L. A.; Ternansky, R. J.; Balogh, D. W.; Kentgen, G. J.
Am. Chem. Soc. 1983, 105, 5446−5450.
(17) Eaton, P. E.; Cole, T. W. J. Am. Chem. Soc. 1964, 86, 962−964.
(18) Sklyarova, A. S.; Rodionov, V. N.; Parsons, C. G.; Quack, G.;
Schreiner, P. R.; Fokin, A. A. Med. Chem. Res. 2012, 22, 360−366.
(19) Gosling, J. I.; Baker, S. P.; Haynes, J. M.; Kassiou, M.; Pouton,
C. W.; Warfe, L.; White, P. J.; Scammells, P. J. ChemMedChem 2012, 7,
1191−1201.
F
dx.doi.org/10.1021/op400181g | Org. Process Res. Dev. XXXX, XXX, XXX−XXX