Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Patent
1994-02-15
1996-05-14
Raymond, Richard L.
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
549 58, 564 8, 564 9, 564301, C07D33356, C07F 502
Patent
active
055169090
DESCRIPTION:
BRIEF SUMMARY
This is a 371 of PCT/US 92/05141, filed Jun. 18, 1992.
FIELD OF INVENTION
This invention relates to the production of amine-boranes. More particularly, the invention relates to the product of a stable, pure, pyridine-borane substantially free of color.
BACKGROUND OF THE INVENTION
Aromatic, aliphatic, alicyclic and aromatic heterocyclic amine-boranes are useful as reducing agents for various substrates, in reductive amination reactions, in the hydroboration of alkenes and alkynes, in procedures for the electroless plating of metals and in the synthesis of ceramic and preceramic materials.
Of particular importance in the context of this invention is the fact that pyridine-borane is a key reagent in the synthesis of zileuton [N-1(1-benzo[b]thien-2-ylethyl)-N-hydroxyurea] ##STR1##
Zileuton is a 5-lipoxygenase inhibitor devoid of cyclooxygenase and 12- and 15-lipoxygenase inhibitory activity. See, e.g., DN&P 4(1):46 et. seq. Pyridine-borane is used in the penultimate step of zileuton synthesis as shown by the following Equation I: ##STR2##
EQUATION I
The various known methods for the production of pyridine-borane are each attended by disadvantages. Pyridine-borane produced by passage of diborane through pyridine is frequently contaminated with by-products and hence unstable and of poor color. Pyridine-borane synthesis in non-aqueous systems, which require large solvent volumes with consequent low through-put also yields an unstable and impure product. Facilitation of the reactions required to produce pyridine-borane By electrolytic or mechanical agitation presents engineering difficulties and safety concerns.
The problems which attend these prior art methods create a need for a new synthesis which yields stable pyridine-borane and other amine-boranes of improved stability and color suitable for use in the synthesis of drugs such as zileuton.
SUMMARY OF THE INVENTION
This invention provides a method for the preparation of highly pure stable amine-boranes. A specific embodiment of the invention provides pure, stable pyridine-borane which is substantially free of color and hence "water white". Pursuant to the invention, pyridine is reacted with an alkali metal borohydride in a weakly acidic aqueous medium to produce a pyridine-borane containing reaction mixture. The pyridine-borane product is then stabilized with a strong base, e.g., aqueous sodium or potassium hydroxide. The pyridine-borane product is azeoptropically dried. Purity, as determined by iodometric titration, is preferably 92-96%. Yield, corrected for purity, is approximately 70-90%.
DESCRIPTION OF THE FIGURE
FIG. 1 is a schematic illustration of one form of apparatus which may be used to practice the invention.
DETAILED DESCRIPTION OF THE INVENTION
The invention entails a combination of steps which yield stable pure substantially water white amine-boranes including pyridine-borane.
Pursuant to the invention, an amine such as di or trialkyl amine, preferably pyridine is reacted with an alkali metal borohydride in a weakly acidic aqueous medium. Hydrogen evolved by the reaction may be released through an oil bubbler or otherwise disposed of.
In the preferred practice of the invention, the reaction vessel is precharged with pyridine. The alkali metal borohydride is added followed by aqueous weak acid. The temperature of the reaction mixture is controlled to maximum of about 30.degree. C. to about 35.degree. C. Evolved hydrogen is released from the system, e.g., through an oil bubbler. The aqueous acid is preferably added over a period of about 2.5 to 3 hours.
An aqueous solution of a strong, preferably inorganic base is added to increase the pH of the reaction mixture and neutralize the excess acid. The neutralized reaction mixture separates into an upper layer containing the pyridine-borane product and a lower aqueous layer which is discarded.
The pyridine-borane product layer is preferably stabilized by addition of and agitation with an aqueous solution of a strong base. The resulting lower aqueous layer is separated and discarded. Ex
REFERENCES:
patent: 3013016 (1961-12-01), Haberlaud et al.
patent: 3127448 (1964-03-01), Hinckley
patent: 4873259 (1989-10-01), Summers et al.
patent: 5036067 (1991-07-01), Girard et al.
patent: 5144032 (1992-09-01), Arduengo
Brown et al, JACS, vol. 64 (1942) pp. 325-329.
Taylor et al, JACS, vol. 77 (1955) pp. 1506-1507.
Boulder Scientific Company
Irons Edward S.
Raymond Richard L.
LandOfFree
Process for producing amine-boranes does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Process for producing amine-boranes, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Process for producing amine-boranes will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-1896871