Highly pure amidoximes

Details Highly pure amidoximes Highly pure amidoximes

1990-11-09

1993-08-24

Ivy, C. Warren

Organic compounds -- part of the class 532-570 series

Organic compounds

Heterocyclic carbon compounds containing a hetero ring...

C07D40112

Patent

active

052390772

DESCRIPTION:

BRIEF SUMMARY
FIELD OF THE INVENTION

This invention relates to an improved process for preparing amidoxime derivatives. ##STR1##
In the formulae used herein, the meaning of the substituents is throughout as follows if not indicated otherwise: alkyl, aralkyl group or optionally substituted and/or condensed aromatic and/or heteroaromatic group; branched chain or cyclic and/or unsaturated C.sub.1-7 alkyl or aromatic group; cyclic and/or unsaturated C.sub.1-7 alkyl or aromatic group; or to 8-membered ring optionally containing other heteroatoms; and


BACKGROUND OF THE INVENTION

It is known that several representatives of amidoxime derivatives of the formula (I) ##STR2## are useful for the treatment of diabetic angiopathy which is practically unique to the present. Other amidoxime derivatives show a blood pressure lowering action, too and, an alpha-blocking effect may also be observed (British patent specification No. 1,582,029; U.S. Pat. Nos. 4,187,220 and 4,308,399). The possibility of the use of these compounds as therapeutic drugs demands an economical preparation which can be carried out on an industrial scale.
It is known that O-substituted derivatives of oximes are usually prepared by employing alkylating agents (Houben Weyl Vol. X/4, pages 217 to 220 (1968). The O-substituted amidoximes according to the present invention have been prepared by reacting amidoximes with epoxides (or their functional equivalents), i.e. with the epoxy compounds of the formula (IV) ##STR3## or with 1-halo-2-hydroxy-3-propanamines of the formula (III) ##STR4## or with 3-hydroxyazetidine salts of the formula (V) ##STR5## respectively. Protic solvents such as water, methanol, ethanol or mixtures of water with a water-immersible solvent, e.g. benzene were used as solvents in these reactions. The final products were isolated by extraction (sometimes after evaporation), the extract was washed several times with a concentrated alkaline solution and after solvent change it was acidified by alcoholic hydrochloric acid and carefully crystallized. The hydrochlorides of the products were obtained in yields between 6% and 50% in this way.
On reproduction and scale increase of these reactions it has surprisingly been found that the amidoximes of the formula (II) ##STR6## could not completely be transformed. After a reaction of about 60 to 70%, the reaction stopped and both an increase in the reaction temperature or use of an excess of reactant enhanced the amount of tarry side products which inhibited the isolation of the product.


DESCRIPTION OF THE INVENTION

Thus, the aim of the present invention is to provide an industrial plant process which is free from the above disadvantages.
It is known from the literature (J. Am. Chem. Soc. 80, 1257 (1958); Appl. Polym. Sci. 11, 145-8 (1967); and J. Chem. Soc. 1950, 2257-2272) that amines of the formula (III) are unstable: on standing they are reversibly transformed to a cyclic salt of the formula (V) or dimerize to a dioxane derivative of the formula (VI) ##STR7##
Concerning the synthesis, the former transformation is not a drawback since amidoximes can be reacted with salts of the formula (V) in the presence of a base. However, the latter transformation is irreversible which can cause a significant substance loss in the synthesis.
One basis of the present invention is the recognition that the compounds of the formulae (III), (IV) or (V), respectively, react also with water, alcohols and acids to give side products of the formula (IX) ##STR8## wherein
R.sup.4 and R.sup.5 stand for hydroxyl, C.sub.1-4 alkoxy, C.sub.2-8 alkanoyl or acid residue.
Depending upon the dimensions of the R.sup.4 and R.sup.5 groups, particularly in the case of a hydroxyl or lower alkoxy group, a polymerization of significant extent can also occur which can lead e.g. to compounds of the formula (XI) ##STR9##
The present invention is based also on the recognition that the appearance of these decomposition products is responsible for "stopping" of the coupling reaction. The appearance of the decomposition products is presumably favor

REFERENCES:
patent: 4187220 (1980-02-01), Takacs
Appl. Polym. Sci. 11, pp. 145-148 (1967).
Monatshefte fur Chemie, 154, pp. 118 to 131 (1894).
Houben Weyl, vol. X/4, pp. 217-220 (1968).
J. Am. Chem. Soc., vol. 80, pp. 1257-1259 (1958).
J. Chem.Soc. 1950, pp. 2257 to 2272.
J. Org. Chem. 33, (2) pp. 523-530 (1968).

Affiliated with

Also associated with

Rating

Highly pure amidoximes does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Highly pure amidoximes, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Highly pure amidoximes will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-830420