Process for making 3,4,5,6-tetrahydrophthalimide derivatives

Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...

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562 20, C07D20948

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active

053248430

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BRIEF SUMMARY
The present invention relates to an improved process for preparing 3-(3,4,5,6-tetrahydrophthalimido)cinnamic esters of the formula I ##STR5## where R.sup.1 is hydrogen or halogen, R.sup.2 and R.sup.3 are halogen, R.sup.4 is a C-organic radical of 1 to 6 carbon atoms and R.sup.5 is hydrogen or methyl.
It is generally known that nitrocinnamic esters which, however, have no alpha halogen are reduced by iron in acetic acid (JP-A 155 358/84) or hydrogen on a palladium, platinum or Raney nickel catalyst (EP-A 345 637 and DE-A 39 31 615) to aminocinnamic esters and these are converted into tetrahydrophthalimidocinnamic esters of the type of compounds I.
However, according to Bull. Chem. Soc. Jap. 49, (1976) 2284, BE-A 855-464 and EP-A 240 659, when hydrogen is used as reducing agent there is also hydrogenation of the unsaturated side chain of an aromatic compound. EP-A 240 659 also discloses that this side reaction does not occur when platinum oxide is used as catalyst or when metals such as iron are used as reducing agents.
In addition, EP-A 369 212 and Chimia 41, (1987) 73 disclose that catalytic dehalogenation is possible with hydrogen in the presence of catalysts such as palladium, platinum and Raney nickel, and this is in fact used for preparative syntheses in these publications.
It is therefore proposed, to avoid the said competing reactions, in the earlier German Application DE-A 39 31 615 that specifically the 3-nitrocinnamic esters II which have alpha chlorine or bromine be reduced only with mild reducing agents such as tin(II) salts or with iron to the 3-amino esters III.
However, the disadvantage of this method is the problem on the industrial scale of removing and disposing of the tin and iron salts which are the byproducts of the reduction.
It is an object of the present invention to provide better access to the compounds I.
We have found that this object is achieved by a process for preparing 3-(3,4,5,6-tetrahydrophthalimido)cinnamic esters of the formula I, which comprises reducing a 3-nitrocinnamic ester of the formula II ##STR6## with hydrogen in the presence of a catalyst, and condensing the resulting 3-aminocinnamic ester of the formula III ##STR7## subsequently or simultaneously with a 3,4,5,6-tetrahydrophthalic anhydride of the formula IV ##STR8##
We have also found novel 3-nitrocinnamic esters of the formula II' ##STR9## where R.sup.1 ' is hydrogen or fluorine, R.sup.2 and R.sup.3 are halogen and R.sup.4 ' is C.sub.1 -C.sub.4 -alkyl, and novel 3-aminocinnamic esters of the formula III' ##STR10## as intermediate.
The 3-nitrocinnamic esters II used as starting materials can be prepared in a variety of ways, preferably by one of the following methods:
(a) reaction of m-nitro aldehydes IV with phosphorus ylides V ##STR11##
The Ar radicals can be identical or different and are C-organic radicals, in particular, phenyl.
The reaction is generally carried out by conventional methods (cf. EP-A 345 637) in an inert solvent or diluent, e.g. alcohols, preferably in R.sup.4 --OH, or in chlorohydrocarbons such as dichloromethane.
All the starting compounds are preferably employed in approximately the stoichiometric ratio, but an excess of one component, of up to 10 mol %, may be advisable in some cases.
The reaction is normally carried out at from 0.degree. C. to the boiling point of the solvent.
No special conditions relating to the pressure are necessary; the reaction is therefore expediently carried out under atmospheric pressure.
The starting compounds IV are known. The phosphorus ylides V can be prepared by conventional methods [e.g. Chem. Ber. 95, (1962) 3003].
(b) Nitration of cinnamic esters VI ##STR12##
The reaction is carried out by conventional methods (cf. also JP-A 155 358/84), if required in an inert solvent or diluent at from -10.degree. to 50.degree. C.
The amount of nitration reagent is not critical. It is preferable to use an excess of nitration reagent in sulfuric acid or without solvent in nitric acid.
The statements concerning the pressure made for method (a) apply. The preparation of

REFERENCES:
patent: 4933001 (1990-06-01), Plath et al.
patent: 4959098 (1990-09-01), Schwalge et al.

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