Organic compounds -- part of the class 532-570 series – Organic compounds – Four or more ring nitrogens in the bicyclo ring system
Patent
1999-05-24
2000-02-15
Ambrose, Michael G.
Organic compounds -- part of the class 532-570 series
Organic compounds
Four or more ring nitrogens in the bicyclo ring system
544238, 560 34, 560145, 560169, C07D23724, C07D40904, C07D40504, C07D40104, C07C22922
Patent
active
060254920
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates generally to a process for making pyridazinone derivatives and a hydrazone aldehyde precursor.
2. Description of Related Art
Certain carboxy substituted 4-oxo-1,4-dihydropyridazines and carboalkoxy substituted 4-oxo-1,4-dihydropyridazines are known in the art to have plant gametocidal activity and plant growth regulatory activity. Current methods for producing the above compounds typically use expensive raw materials and/or result in low yields of product. For example, U.S. Pat. Nos. 4,707,181; 5,026,880; and 4,732,603 disclose preparing the above compounds by reacting a 2-phenylhydrazono-3-oxoglutarate with an organic acid chloride in the presence of a Grignard reagent (isopropyl magnesium chloride). The Grignard reagents are expensive and low yields are obtained. U.S. Pat. Nos. 5,189,163 and 5,010,192 also disclose using expensive raw materials, such as methyl-3-oxopentanoate, and result in low yields.
The present invention provides a more efficient process for making pyridazinone derivatives which results in higher yields of product and uses lower cost raw materials, hydrazone aldehyde and diazo acetate.
Hydrazone aldehydes are useful as precursors in the production of the carboxy substituted 4-oxo-1,4-dihydropyridazines and carboalkoxy substituted 4-oxo-1,4-dihydropyridazines mentioned above. Such hydrazone aldehydes, such as 4-chlorophenylhydrazone aldehyde (ethanedial, mono[(4-chlorophenyl)hydrazone]), have typically been made by batch processes, wherein one reactant is added to a reactor containing the other reactant. However, such batch processes lead to a lower payload (2-5%). An increase in the payload above 5% made the reaction slurry difficult to mix and thus resulted in by-product formation. In addition, the water content of the resulting solution is about 80% in a batch process, making the solution difficult to wash and handle, and causing filtration of the product to be very slow. The high water content also leads to very long drying times of the product.
An improved process to produce hydrazone aldehydes having a decreased water content would lead to a solution which is easier to handle, and decreased filtration and drying times of the product.
SUMMARY OF THE INVENTION
The present invention relates to the synthesis of a hydrazone .beta.-keto ester by the reaction of a diazo ester with a hydrazone aldehyde in the presence of a Lewis acid. In a preferred embodiment, the hydrazone .beta.-keto ester is then converted into a pyridazinone compound by the reaction with an alkyl acid chloride in the presence of a base, followed by acidification.
More particularly, the present invention relates to the synthesis of a hydrazone .beta.-keto ester having the general Formula III: ##STR1## by reacting a diazo ester with a hydrazone aldehyde in the presence of a Lewis acid.
The hydrazone .beta.-keto ester can then be reacted with an alkyl acid chloride in the presence of a base, followed by acidification to produce pyridazinone compounds having the general Formula I: ##STR2## or the general Formula II: ##STR3##
The present invention also relates to a continuous process for the production of a hydrazone aldehyde comprising contacting a hydrazine and glyoxal, wherein the hydrazine and the glyoxal are added simultaneously to a reactor at a controlled rate, preferably between about 10 mL/min and about 100 mL/min.
DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS
The present invention relates generally to a process for making pyridazinone derivatives and preferably to a process for making a compound of Formula I: ##STR4## wherein R.sub.1 is an alkyl, cycloalkyl, aryl or heteroaromatic group; R.sub.2 is an alkyl group; and R.sub.3 is an alkyl or phenyl group. Alkyl groups useful in the processes of the present invention include straight-chain, branched-chain or cyclic alkyl groups having between about 1 and 12 carbon atoms. Preferably the alkyl groups have from 1 to about 5 carbon atoms. Aryl in a given case can be phenyl and can be
REFERENCES:
patent: 4707181 (1987-11-01), Patterson
patent: 4962199 (1990-10-01), Yalamanchili
patent: 5189163 (1993-02-01), Cox et al.
Abbass, Ikhlass M. et al. (1992) "Synthesis of Pyrazolo [4,5}pyridazine and Isoxazolo [3,4d ]pyridazine Derivatives," Arch. Pharm. Res. 15(3):224-228.
Holmquist, Christopher R. et al. (1989) "A Selective Method for the Direct Conversion of Aldehydes into .beta.-Keto Esters with Ethyl Diazoacetate Catalyzed by Tin(II) Chloride," J. Org. Chem. 54(14):3258-3260.
Clark Jerry D.
Ma Yinong
Patelis Lefteris
Peterson James C.
Shah Ajit S.
Ambrose Michael G.
Monsanto Company
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