Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
2001-02-27
2002-08-13
Morris, Patricia L. (Department: 1625)
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
active
06433176
ABSTRACT:
FIELD OF INVENTION
The present invention relates to 8-hydroxyjulolidine and its analogous compounds and preparation thereof, especially to a one-step cyclization reaction of 3-aminophenol or 1,3-dihydroxyaniline with 1,3-dihalopropane or its analogs to prepare the desired julolidines. The 8-hydroxyjulolidine and its analogous compounds have the following chemical structure:
wherein R
1
and R
2
represent independently hydrogen, halogen, hydroxyl group or alkyl groups.
BACKGROUND OF INVENTION
Coumarins are often used as lasing dyes and fluorescent probes in bioassays, because they exhibit the beneficial properties of tunable wavelengths, high quantum yields, high absorption coefficient and little overlapping in the absorption and emission spectra. According to U.S. Pat. No. 3,873,940, U.S. Pat. No. 3,932,415, U.S. Pat. No. 4,005,092, U.S. Pat. No. 4,471,041, U.S. Pat. No. 4,736,032 and U.S. Pat. No. 4,794,184, coumarin compounds with fused and rigid nitrogen-containing rings significantly hinder the mobility of amino groups and thus reduce the energy dissipation caused by the rotation of uncyclized amino groups. Such rigid coumarins also greatly increase the dipolar moments in the excited states, and thus attain high quantum yields and emission efficiencies in lasing.
However, there are only a few methods for the preparation of 8-hydroxyjulolidine and 8,10-dihydroxyjulolidine have been disclosed. In the conventional art, method for the preparation of these compounds, such as those disclosed in U.S. Pat. No. 4,005,092 , U.S. Pat. No. 4,471,041 and
Journal of Organic Chemistry
(1987) Vol. 52, pp. 1465-1468, 8-hydroxyjulolidine and 8,10-dihydroxyjulolidine are prepared by cyclization of m-anisidine (or 3,5-dimethoxyaniline) with excess amounts of 1-bromo-3-chloropropane, followed by demethylation with strong acids. Using dimethyl sulfate for methylations of 3-aminophenol and 3,5-dihydroxyaniline is generally carried out to obtain m-anisidine and 3,5-dimethoxyaniline.
The above-mentioned methods have several disadvantages. First, in the mass production of 8-hydroxyjulolidine or 8,10-dihydroxyjulolidine, excess 1-bromo-3-chloropropane (7.6-15 molar proportions) is used. Such an approach will bring out relatively higher production costs. Secondly, in the step of demethylation corrosive strong acids such as hydrochloric acid, hydroiodic acid and boron tribromide are needed. These materials are hazardous to the environment. Thirdly, the overall yields in the above-said approaches are low (<30%) due to the need of two extra steps, prior protection of the hydroxyl group with a toxic reagent of dimethyl sulfate and removal of the protecting methyl group after the cyclization reaction.
It is thus necessary to provide a novel method for the preparation of 8-hydroxyjulolidine and its analogous compounds wherein preparation costs may be reduced.
It is also necessary to provide a method for the preparation of 8-hydroxyjulolidine and its analogous compounds wherein no hazardous material is needed.
It is also necessary to provide a method for the preparation of 8-hydroxyjulolidine and its analogous compounds wherein yields of preparation may be improved.
It is also necessary to provide a simplified method for the preparation of 8-hydroxyjulolidine and its analogous compounds.
OBJECTIVES OF INVENTION
The objective of this invention is to provide a simplified method for the preparation of 8-hydroxyjulolidine and its analogous compounds wherein only one single step reaction is needed.
Another objective of this invention is to provide a novel method for the preparation of 8-hydroxyjulolidine and its analogous compounds wherein preparation costs may be reduced.
Another objective of this invention is to provide a method for the preparation of 8-hydroxyjulolidine and its analogous compounds wherein no hazardous material is needed.
Another objective of this invention is to provide a method for the preparation of 8-hydroxyjulolidine and its analogous compounds wherein yields of preparation may be improved.
SUMMARY OF INVENTION
According to this invention, a novel method for the preparation of 8-hydroxyjulolidine and its analogous compounds is disclosed. In the invented method, desired julolidines may be easily prepared by a single-step cyclization reaction, without the need of steps such as prior protection of hydroxyl groups or removal of the methyl groups. The invented method discloses an alkylative cyclization reaction at the amino group of the reactant whereby the hydroxyl group of the reactant will not be affected. As a result, yield of the invented method may be higher than that of the conventional method. The invented method comprises the following chemical reactions:
wherein X and Y represent independently halogen, acyloxyl, sulfonyloxyl or phosphoryloxyl group, and R
1
and R
2
represent independently H, halogen, hydroxyl, or alkyl group. In the reaction solution, an organic alkali, an inorganic alkali or a phase-transfer agent may be added. Suitable additives include triethylamine, LiOH, Na
2
CO
3
, NaHCO
3
, organic ammonium salts and organic sulfonates.
The products of this invention have the following structure:
wherein R
1
and R
2
are defined as above.
The invented method comprises a cyclization reaction of 3-aminophenol or 1,3-dihydroxyaniline with 1,3-dihalopropane or its analogs.
This invention also discloses a method of recrystallization or a solid-liquid continuous extraction of 8-hydroxyjulolidine and its analogous compounds to obtain purified products.
This invention also discloses a method for the preparation of various coumarins by further treatment of the resulting 8-hydroxyjulolidine and its analogs with appropriate reagents such as malonate and acetoacetate. This invention also discloses the products and intermediates prepared therefrom.
DETAILED DESCRIPTION OF INVENTION
REFERENCES:
patent: 4005092 (1977-01-01), Reynlds
patent: 4471441 (1984-09-01), Baranyl et al.
Chen Chao-Tsen
Fang Jim-Min
Lu Ling
Tang Shao-Tzu
Allied Industrial Corp., Ltd.
Bacon & Thomas
Morris Patricia L.
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