IL26284A - Fumaramic acid derivatives - Google Patents

Description

u ACID The instant invention relates to new compositions of matter and their method of More the invention describes acids and derivatives These compounds are useful as plant growth regulants and The disubstituted radicals may be or and one of the carbons of the intermediate carbons of the fumaramic acid may contain a lower salts and esters of the fumaramic acids as well as salts of these esters with strong mineral acids are within the scope of the The fumaramic acids are prepared by the isomerization of a strong acid salt of the corresponding maleamic These latter compounds may be prepared as described in S Included within the scope of the in addition to the free are their equivalent such as the alkali alkali alkaline earth ammonium or amine methyl dimethyl trimethyl ethyl ethanol diethanol or ethanol ammonium The salts may readily be formed directly from the acid and a selected base such as an alkalimetal hydroxide or or or an amine by protonation of the disubstituted Such salts Include for example the hydrohallde and The esters of the fumaramic such as the esters having 1 to 12 carbon atoms in the and the alkenyl esters having 3 to 4 carbon atoms in esterifying radical may be used as plant growth the allyl and allyl The esters may be formed by esterifying the selected fumaramic acid with the selected or directly from the maleamic acid or maleimide component by performing the in an alcoholic the salts of these esters with strong mineral acids have been The fumaramic acids of the present invention may be represented by the general formu la wherein and each stand for an alkyl having 1 to 12 carbon atoms or and 2 compositely stand for a or and and each stand for or of and stands for hydrogen and the other stands for a lower alkyl group having 1 to 8 carbon Examples of chemicals of the present invention are DimethylaminoJ acid acid acid acid acid maramic acid Sodium Calcium Isopropyl dimeth fumaramate Ethyl hydrochloride acid Ethyl Diethanolammonium salt of acid Allyl hydrochloride ethallyl hydrochol It is well known that maleie acid and many of its simple derivatives can be rearranged to the fiimaric form by heating with catalytic amounts of halogen Lewis acids sulfu and sulfur as well as by catalytic surfaces in noble metal By using these known methods in several attempts to effect the desired arrangement in the case of no rearrangement was The use of by weight of iodine in refluxing acetonitrile resulted only in the recovery of unchanged starting Replacement of the iodine by sulfur in a similar procedure resulted in extensive decomposition and No ment was achieved when acid was refluxed in acetonitrile in the presence of by weight hydrolysis and the formation of fumaric In accordance with the it has been discovered that the pounds of the instant invention may be prepared by the rearrangement of the maleamic wherein the latter disubstitutedamino group has been protonated a The reaction must be carried out in an reaction The ted maleamic form may then be rearranged with several known maleic acid isomerization The of the disubstituted amino group of the maleamic form may be readily achieved by forming an acid salt with strong acids which do not cause adverse side effects such as or The hydrogen halide salts are the most preferable particularly the hydrogen chloride and the hydrogen Inert reaction mediums include any liquid which will not or dehydrate the Examples of these are the lower carboxyllc acids and the halosubstituted carboxyllc such as glacial acetic propionic acid and Various other solvents can be used depending on the physical ties of the particular substituted amino maleamic vative to be The are obtained with glacial acetic acid and If the desired products are the esters the the appropriate alcohol can be used as the reaction It is thus possible to effect both of the acid its imide and the this case the solvent is strictly it does permit the formation of the basic fumaramic The isomerization of the maleamic form to the fumaramic form may be carried out in the presence of maleic acid isomerization lysts which may be used include hydrohalic and aluminum The catalytic isomerization is carried out at a temperature of from 20 to preferably from to in the presence to of preferably to by The following examples serve to more specifically illustrate the instant Example I Preparation of Acid When a partial solution of of maleamic acid in 40 of glacial acetic acid was treated with anhydrous HC1 until had been there sulted complete solution of all the solid in the warm The molar excess of the HC1 served as the After heating to on a steam plate for a solid crystalline mass had This mixture was then allowed to cool to room temperature over 1 hour and then treated with 30 of The cake was broken and the resulting slurry cooleid in an ice bath for Filtration and washing with 50 of cold acetonitrile gave 17 of acid hydrochloride as colorless crystals Pound 97 This product readily dissolves in water to give a strongly acidic When a solution of 5 of this product in 10 of water was treated with concentrated aqueous until the pH of the solution had been raised to there resulted the precipitation of acid as a white tration and washing with cold water gave of less crystals of Example II To partial solution of of acid 50 of glacial acetic acid was added anhydrous HCl until had been After adding of iodine the resulting yellow solution was heated on a steam plate to for and then allowed to cool to room temperature over 2 followed by washing with gave 14 acid hydrochloride as colorless crystals of Example III To a suspension of of maleamic in 35 of glacial acetic acid was added of anhydrous To the resulting clear solution was added of anhydrous Within minutes after placing on the steam plate the contents of the flask set to a solid mass of white After allowing to at room temperature 1 hour the cake was broken and 30 of acetonitrile was followed by washing with gave of These three examples show that practicing this new process it is essential to completely neutralize the hydrazine moiet as the salt of a strong mineral acid and that the cis to trans rearrangement can subsequently be catalyzed by small amounts of maleic acid isomerization catalysts such as hydrogen Esters of acid are readily prepared by refluxing the hydrochloride salt with the appropriate alcohol to yield the ester hydrochloride from which the free ester can be liberated by the addition of base to an aqueous solution of the ester In this manner the following esters were l hydrochloride 13 Example IV Preparation of acid To a mixture of 12 of acid hydrochloride of glacial acetic acid was added of When heated to for 1 the solid initially sent soon dissolved completely and then a new solid gradually After adding 20 of trile and cooling in an ice bath for tion gave of acid drochloride as colorless crystals of of water there was gradually added sufficient aqueous ammonia to raise the pH to The solid which cipitated was collected by filtration and washed with cold There was obtained of Example V Preparation of hydrochloride To a partial solution of 03 of citraconamic acid in of glacial acetic acid was added of anhydrous As the introduction of the HC1 was all of the solid dissolved in the warm solution and then suddenly a new precipitate formed After allowing to stand for 20 15 of acetonitrile added and the mixture cooled in an ice bath for Filtration yielded of acid hydrochloride as colorless crystals of Example VI Preparation of acid When a mixture of 10 of acid and 80 of glacial acetic acid was heated to complete solution of the solid Into this hot solution was passed anhydrous HCl until had been This resulted in a rise in temperature of the mixture to and the precipitation of a small amount of the hydrochloride Heating to caused complete solution of all At this point of was This caused the rapid formation of a After continuing heating to for 15 Subsequent cooling in an ice followed b filtration and washing with gave 10 of acid hydrochloride as less crystals of This upon treatment with readily hydrolyzes to HCl and acid which precipitates as colorless crystals of Example VII This example demonstrates that fumaramlc acid hydrochloride can be prepared in one tion from 1 and anhydrous HCl without isolating the intermediate To a solution of 9 50 of maleic anhydride in 100 of glacial acetic acid was gradually added a mixture of 30 50 of 1 zine and 75 of glacial acetic This latter mixture was prepared by the gradual with of the 1 to the acetic While adding this mixture to the solution of maleic anhydride in acetic cooling was employed so that the temperature of the reaction mixture did not o exceed The resulting clear yellow solution was allowed to stand at room temperature for 15 When 19 of anhydride HCl was passed into this the temperature rapidly rose to After standing for hour the original pale yellow tion had set to a solid mass of white After standing for an additional 1 100 of acetonitrile was added and the resulting slurry The filter cake was washed with 50 of acetonitrile then with of acid hydrochloride o colorless crystals of Example VIII The rearrangement may carried out in in a manner similar to that using acetic To a suspension of of malea ic acid in 20 of acetonitrile was added mol of hydrogen chloride The mixture became warm and the solid Warming the tion on a steam bath resulted in some precipitate tion with 5 minutes Precipitate formation was complete in 15 After adding 20 ml of filtration of the slurry yielded fumaramlc acid hydrochloride identified by its infrared Example IX To a suspension of of methylaminomaleamic acid in 100 of methanol was added of hydrogen Solution of the solid occurred upon heating to After 15 of refluxing the methanol was removed having a oily This was dissolved in water and the solution then made slightly basic by the tion of dilute The resultant precipitate was filtered and identified as fumaramate l and by its infrared Example X The isomerization and esterification are ried out in one step in this example follcw s To a solution of of in 50 of ethanol was added was refluxed for hours and then concentrated by removal of the methanol reduced pressure The addition of ether caused the precipitation of an oil which There was obtained of hydrochloride identified by its infrared Example XI A suspension of of aminomaleamic acid in 25 of acetonitrile was treated with mole anhydrous hydrogen Upon initial warming on a steam bath solution After a few minutes there precipitated a solid of o Conversion of the salt to the free base yielded acid insufficientOCRQuality

Claims (1)

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