Organic compounds -- part of the class 532-570 series – Organic compounds – Carboxylic acid esters
Reexamination Certificate
1999-05-04
2001-03-06
Shah, Mukund J. (Department: 1624)
Organic compounds -- part of the class 532-570 series
Organic compounds
Carboxylic acid esters
C568S811000, C568S807000, C568S810000
Reexamination Certificate
active
06197994
ABSTRACT:
BACKGROUND OF THE INVENTION
The present invention relates to silica gel supported bis-cinchona alkaloid derivatives and a preparation method and use thereof. More particularly, the present invention relates to silica gel supported bis-cinchona alkaloid derivatives of the formula III by chemically reacting formula I as a chiral monomer with silica gel of the formula II. The present invention also relates to the use of the formula I as a catalyst in synthesizing optically-active vicinal diols by asymmetric dihydroxylation reaction of olefins.
The asymmetric dihydroxylation of olefins using catalytic amounts of osmium tetraoxide or potassium osmate dihydrate in the presence of cinchona alkaloid derivatives allows access to a wide variety of optically pure vicinal diols [(a) Johnson, R. A. and Sharpless, K. B. Catalytic Asymmetric Dihydroxylation. In Catalytic Asymmetric Synthesis; Ojima, I., Ed.; VCH publishers: New York, 1993 pp 227-272, (b) Chem. Rev., 1994, 94, 2483-2547, (c) Tetrahedron: Asymmetry, 1992, 3, 1317-1349]. However, there are limitations to performing the catalytic AD reaction in synthesizing vicinal diols on a large scale due to the toxicity and high cost of osmium tetraoxide or potassium osmate dihydrate and the cinchona derivatives. By employing the heterogeneous catalytic systems, it was expected to cost-down by using osmium tetroxide and bis-cinchona alkaloids repetitively. To this end, several polymer-bound cinchona alkaloid derivatives have been developed. However, these heterogeneous catalytic systems did not have practical applicability since most of the polymers require complicated synthetic manipulations and, moreover, their catalytic efficiency and enantioselectivity were much worse than those of the homogeneous catalytic systems [(a) Tetrahedron Lett., 1990. 31, 3003, (b) Tetrahedron Lett., 1991, 32, 5175, (c) Tetrahedron Lett., 1992, 33, 5453, (d) Tetrahedron: Asymmetry, 1993, 4, 2351, (e) Tetrahedron Lett., 1994. 35, 6559.
SUMMARY OF THE INVENTION
It is an object of the present invention to develop heterogeneous bis-cinchona alkaloid derivatives that can be prepared by simple procedures, are economical with an improved catalytic efficiency for asymmetric dihydroxylation of olefins, are reusable and have high thermal and mechanical stabilities.
It is another object of the present invention to provide the silica gel supported bis-cinchona alkaloid derivatives.
Further, another object of the present invention is to provide a method of preparing the silica gel supported bis-cinchona alkaloid derivatives.
Another object of the present invention is to provide a method of using the silica gel supported bis-cinchona derivatives as a catalyst in the asymmetric dihydroxylation of olefins.
The manner in which the foregoing and other objects of this invention are accomplished will be apparent from the accompanying specification and claims considered together with the working examples.
DETAILED DESCRIPTION OF THE INVENTION
To achieve the objects described above, new bis-cinchona derivatives represented by the formula I were developed.
(wherein Y is quininyl or quinidinyl; X is null or an unsaturated cyclic compound having 4 carbons, and thus forms pyridazine or phthalazine, respectively)
The examples of the bis-cinchona alkaloid derivatives of the formula I are 1,4-bis(9-O-quininyl)phthalazine, 1,4-bis(9-O-quinidinyl)phthalazine), 3,6-bis(9-O-quininyl)pyridazine and 3,6-bis(9-O-quinidinyl)pyridazine of the formulas 1a, 1b, 1c and 1d, respectively.
Aforementioned bis-cinchona alkaloid derivatives of the formulas 1a~1d were prepared as follows.
Pure 1,4-bis(9-O-quininyl)phthalazine of the formula 1a was obtained by refluxing 1,4-dichlorophthalazine with quinine in dry toluene in the presence of potassium carbonate and potassium hydroxide.
Pure 1,4-bis(9-O-quinidinyl)phthalazine of the formula 1b was obtained by refluxing 1,4-dichlorophthalazine with quinidine in dry toluene in the presence of potassium carbonate and potassium hydroxide.
Pure 3,6-bis(9-O-quininyl)pyridazine of the formula 1c was obtained by refluxing 3,6-dichloropyridazine with quinine in dry toluene in the presence of potassium carbonate and potassium hydroxide.
Pure 3,6-bis(9-O-quinidinyl)pyridazine of the formula 1d was obtained by refluxing 3,6-dichloropyridazine with quinidine in dry toluene in the presence of potassium carbonate and potassium hydroxide.
Following silica gel supported bis-cinchona alkaloid derivatives were prepared by the reaction of chiral monomer of the formula I with mercaptopropylsilanized silica gel of the formula II.
(wherein Y is quininyl or quinidinyl; X is null or an unsaturated cyclic compound having 4 carbons, and thus forms pyridazine or phthalazine, respectively; and R represents methoxy, ethoxy or methyl).
Detailed description of the preparation method of the silica gel supported bis-cinchona alkaloid derivatives of the formula III is as follows. One of the compounds of the formulas 1a-1d as a chiral monomer was refluxed for two days in chloroform with mercaptopropylsilanized silica gel of the formula II in the presence of 2,2′-azobisisobutyronitrile (AIBN) as a radical initiator. Pale yellow powder was obtained as a reaction product. The best equivalent weight (Eq. Wt.) ratio between the chiral monomer and the mercaptopropylsilanized silica gel is 1:2 to consider the economical aspects. Mercaptopropylsilanized silica gel of the formula II was prepared by using the similar procedure as described earlier (P. Salvadori, J. Chromatogr., 1985, 348, 79) by reacting silica gel with (3-mercaptopropyl)trimethoxysilane, (3-mercaptopropyl)triethoxysilane or (3-mercaptopropyl)methyidimethoxysilane in the 1:1 (v/v) anhydrous pyridine-toluene mixed-solvent system.
The newly prepared silica gel supported bis-cinchona alkaloid derivatives contain ca. 1 to 3% of nitrogen as indicated by elemental analysis. The mercaptopropylsilanized silica gel of the formula II can be obtained from any kind of silica gel. However, it is recommended that the adsorbed water should be removed by heating the silica gel to ca. 130~140° C. under vacuum (10~0.001 torr).
The silica gel supported bis-cinchona alkaloid derivatives of the formula III can be exemplified by the following formulas IIIa, IIIb, IlIc and IIId.
(wherein R represents methoxy, ethoxy or methyl; Me is methyl).
The chemicals represented by the formula III of the present invention, i.e., all of the newly prepared silica gel supported bis-cinchona alkaloid derivatives of the formulas Ia-Id, have excellent catalytic efficiency and high enantioselectivity in the asymmetric dihydroxylation reaction of olefins (see Table 1). Moreover, the complex between the silica gel supported bis-cinchona alkaloid derivatives of the formula III and osmium tetraoxide can be separated from the reaction mixture by filtration after the reaction. Therefore, the catalysts can be reusable since the efficiency, especially the enantioselectivity is maintained.
By utilizing the silica gel supported bis-cinchona alkaloid derivatives of the formula III as exemplified by formulas 3a-3d, the catalytic asymmetric dihydroxylation reaction of olefins provides a much simpler and more economical choice than the reaction using the conventional homogeneous catalytic systems.
REFERENCES:
S.C.Eui etal.Silica gel supported Bis-Cin.alkaloid: ahly.effi..Tetrah.Asymm.8(6),841-44. Mar. 1997.
S.C.Eui etal.Efficient & practi.polymer.cat.for hetero.asymm . . . Tetrah.Asymm.7(3),645-8,1996, Mar. 1997.
R. A. Johnson et al, “Catalytic Asymmetric Dihydroxylation” in Catalytic Asymmetric Synthesis, I. Ojima ed., VCH Publishers, New York, pp. 227-272, (1993).
H.C. Kolb et al, “Catalytic Asymmetric Dihydroxylation”,Chem. Rev., 94, pp. 2483-2547 (1994).
B.B. Lohray, “Recent Advances in the Asymmetric Dihyroxylation of Alkenes”,Tetrahedron: Asymmetry, vol. 3, No. 11, pp. 1317-1349, (1992).
B.M. Kim et al., “Heterogeneous Catalytic Asymmetric Dihydroxylation: Use of a Polymer-Bound Alkaloid”,Tetrahedron Letters, vol. 31, No. 21, pp. 3003-3006, (1990).
D. Pini et al
Song Choong Eui
Yang Jung Woon
Korea Institute of Science and Technology
Morrison & Foerster / LLP
Patel Sudhaker B.
Shah Mukund J.
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