Patented Nov. 11, 1,941‘ 2,262,262

UNITED STATES PATENT OFFICE 2,262,262 PROCESS OF MAKING MALEANILS John H. Speer, Niles Center, 111., assignor to Na tional Aniline and Chemical Company, Inc., New York, N. Y., a corporation of New York No Drawing. Application August 19, 1939, Serial No. 291,003 8 Claims. (Cl. 260-—313) This invention relates to a process of making mides is preferred. Thionyl chloride, a preferred maleanils, that is, the class of compounds rep treatment agent, has a boiling point of 78° C. resented by the general formula: Preferably the maleanilic acid to be treated is suspended in a suitable liquid medium, which is inert to the reacting materials, and while the mixture is maintained at a temperature between 160° and 200° C., the selected acidyl chloride or in which R is a substituted or unsubstituted aryl bromide treatment agent is gradually introduced radical, from the corresponding maleanilic acids, until the reaction is complete, which will be in represented by the general formula: 10 dicated when the formation of hydrogen chloride or bromide gas ceases. The treatment agent may be added directly to the mixture, or may be volatilized and mixed with a stream of dry air It is known that maleanilic acids react with or other suitable gas and the resulting stream acidyl chlorides to form chlorsuccinanils and to 15 of gas and vapor may be passed into the mixture form isomers of the maleanils. The latter may of maleanilic acid and liquid medium. be represented by the formula: I prefer to use an inert solvent which with the maleanilic acid forms a mixture boiling between 160° and 200° C., and to maintain the reaction 20 mixture automatically at a temperature within cH-ooll 2) this range by maintaining the mixture in a boil ing state. By conducting the reaction in a vessel See, for instance, Gazetta Chimica Italiana 28, provided with a re?ux condenser, loss of solvent II, pp. 189-192; Annalen der Chemie, 309, p. 347; is prevented and the hydrogen chloride or hydro and Atti della Reale Accademia dei Lincei, (5), 25 gen bromide which is evolved is expelled from 18, II, pp. 312-326. For this reason treatment of the chamber through the condenser. Commer maleanilic acids with acidyl chlorides (or with cial dichlorbenzene has been found to be very acidyl bromides) has not been applied to the preparation of maleanils. satisfactory for use as a solvent, and I prefer to use ortho-dichlorbenzene, which has a boiling or According to my invention a maleanilic acid 30 re?uxing temperature of about 180° C. Other corresponding to the desired maleanil is con examples of inert solvents having suitable re?ux verted into the latter by treatment with an or boiling temperatures are tetralin, kerosene, and ganic or inorganic acidyl chloride or acidyl bro commercial cymene. Although the character of mide at a temperature between about 160° ‘and the particular maleanilic acid being reacted and about 200° C. ‘its reaction product may alter the boiling tem I have discovered that at temperatures between perature of a solution, it is possible even in ex about 160° and about ‘200° C. maleanils are ob treme cases, by providing suf?cient solvent, to tained in substantial yields from the treatment adjust the boiling temperature of the solution of maleanilic acids with acidyl chlorides or bro to approximately that of the solvent. At the end mides, and without any accompanying substan of the reaction, continued boiling of the solvent tial production of chlorsuccinanils or bromsuc mixture under re?ux will serve to drive off the cinanils, or isomers of maleanils. At such tem remaining hydrogen chloride or hydrogen bro peratures the addition of hydrogen chloride and mide and other volatile undesired substances hydrogen bromide to the maleanil product is present, following which the solvent may be apparently inhibited and the hydrogen chloride removed by distillation under atmospheric pres or bromide formed as a reaction vproduct is sure, or in any other suitable manner. largely driven off from the reaction mixture as My invention also contemplates conducting formed. the reaction in liquid media which boil sub Examples of acidyl chlorides and acidyl bro stantially above 200° 0., for example, solutions mides are: thionyl chloride (S0012), phosphorus employing, as solvent, naphthalene or molten trichloride (P013), acetyl chloride (CI-130001), paraffin. Such solutions must be maintained at thionyl bromide, phosphorus tribromide, and a temperature below the normal boiling point in acetyl bromide. The substances listed are all order to provide a suitable reaction temperature. readily volatile, boiling below 200° C., and the By conducting the reaction under pressure su?i use of such volatile acidyl chlorides and bro cient to raise the boiling point to the desired re 2 2,262,262 action temperature, media having boiling points through the refluxing mixture of solvent and below the desired reaction temperature may be maleanilic acid. The latter gradually dissolved. used. 125 parts of the thionyl chloride were vaporized Upon completion of the reaction, the residual and introduced into the re?uxing mixture in hydrogen chloride or hydrogen bromide is driven this manner, reacting with the maleanilic acid off by continued heating, together with any ex to form maleanil, sulfur dioxide, and hydrogen cess acidyl chloride or acidyl bromide if a readily chloride, the latter two reaction products large volatile form has been used. When thionyl chlo ly passing off through the re?ux condenser. In ride or bromide is used, sulfur dioxide will be order to remove residual sulfur dioxide and hy formed as one reaction product thereof and is 10 drogen chloride from the mixture, re?uxing was readily driven off along with the hydrogen chlo continued for about one hour after the last of ride or bromide during the course of the reaction the thionyl chloride had been passed into the and during the subsequently continued heating, _ mixture. . so that no reaction products from the acidyl The bulk 'of the dichlorbenzene solvent was chloride or bromide will remain. When phos 15 then removed by distillation at atmospheric phorus trichloride or tribromide is used, a re pressure, and the resultant residual mixture was sidual amount of phosphorus-containing mate-Z ‘distilled in vacuo. Fractional distillation at 5 rial will remain and can be removed by cooling . mm. (mercury) pressure was employed for sepa the mixture and washing with a weakly alkaline . ration of the maleanil, the fraction distilling o? solution (such as an aqueous 5% to 10% sodium 20 between 140° and 155° C‘. being collected sepa-‘ carbonate solution) and then with water. rately as crude maleanil. The yield was 82 parts. The resultant solvent mixture may be freed of The crude product was a bright yellow crystal solvent by distilling off the latter at atmospheric line solid having a freezing point of 85° C. It was pressure or lower. When a solvent having a boil dissolved in and crystallized from alcohol, yield ing puri?ed maleanil which was found to have a ing point substantially in excess of 200° C. has 25 been used, care should be taken not to allow melting point of 895° C. the temperature of the mixture to greatly ex Example 2.-—-60 parts of the mono-metachlor ceed 200° C‘. for an appreciable time, as other anilide of maleic acid, having the formula: wise substantial decomposition of the maleanil will occur. 30 The distillation residue contains the maleanil product and the latter is separated out in any were suspended in 330 parts of commercial ortho dichlorbenzene, the mixture was heated to its convenient manner. For example, the residue refluxing temperature of about 180° C, and a may be subjected to fractional distillation under stream of dry air carrying the vapors from 33 vacuum (such as 4 mm. to 5 mm. mercury abso 35 lute pressure) and the fraction containing the parts of thionyl chloride was passed through the bulk of the maleanil may be isolated as the crude mixture, in the manner described in Example 1. maleanil product. The latter may be puri?ed by -After removal of the solvent dichlorbenzene by crystallization from alcohol to yield a substan distillation at atmospheric pressure, the residue was distilled in vacuo and the fraction which dis tially pure maleanil. 40 The following examples illustrate the prepa tilled between about 170° and about 183° C. at ration of typical maleanils from corresponding 5 mm. pressure was collected separately as the desired product. This product, which was sub maleanilic acids in accordance with my inven stantially 3’-chlor-l~maleanil, having the for tion. In these examples, “parts” means parts mula: by weight. ‘ Example 1.—This example illustrates the prep aration of maleanil using maleic anhydride and aniline as the raw materials to form maleanilic acid, which is then converted into maleanil by interaction with thionyl chloride, both reactions was very soluble in hot, sparingly soluble in cold, being conducted in dichlorbenzene which does alcohol. It was crystallized from an alcoholic not enter into the reactions. The reactions in solution as pale yellow prisms having a melting volved in this combined process may be repre point of 93° C. sented as follows: Example 3.—Using the same procedure as in 55 the preceding example, the mono-2',3'-methyl chloranilide of maleic acid was suspended in boiling commercial dichlorbenzene and was con verted by means of thionyl chloride to the cor responding 2'-methyl-3'-chlor-l-maleanil: 60

(Maleanil) CH—CO/11211430 | In a suitable apparatus‘ ?tted with an agita CH: 01 tor and a re?ux condenser, 98 parts of maleic 65 which was separated from the residue, after re anhydride were dissolved in 665 parts of com moval of the solvent, by distillation in vacuo. mercial ortho-dichlorbenzene (which served as The portion boiling at 4 mm. pressure between the inert solvent). The solution was rapidly agi 160° andv175° C‘. was collected separately‘ as the tated and 93 parts of aniline were slowly added, fraction containing the desired maleanil. After reacting with the maleic anhydride to form male 70 crystallizing the product from alcohol, the puri anilic acid, and the resulting slurry was then ?ed maleanil was an almost white crystalline heated to the boiling or re?uxing temperature solid having a melting point of 695° C. , ' of about 180° C. A dry stream of air was passed Example 4.—-This example illustrates ‘the use through a vessel containing thionyl chloride of phosphorustrichloride (boiling pomwso o.) warmed to‘ about 60° C. and then passed slowly 75 in place of thionyl chloride as the treatment 2,262,262 3 agent. The procedure of Example 1 was em treating said maleanilic acid with thionyl chlo ployed, the same substances and amounts being ride at a temperature of about 160—200° C‘. used except that 55 parts of phosphorus trichlo 3. A process of converting a maleanilic acid ride were used in place of 125 parts of thionyl into the corresponding maleanil, comprising chloride. When the reaction was complete and 5 treating said maleanilic acid with phosphorus substantially all the remaining hydrogen chloride trichloride at a temperature of about ISO-200° C. driven off by continued re?uxing, the dichlorben 4. A process of converting a maleanilic acid zene mixture was cooled and shaken with sev into the corresponding maleanil, comprising eral portions of a 10% by weight solution of treating said maleanilic acid with phosphorus soda ash, and then with water. The aqueous 10 tribromide at a temperature of about 160-200“ C. additions were allowed to settle and were removed 5. A process of making maleanils comprising from the oily layer. The latter was then dis contacting a solution of a maleanilic acid in an tilled under atmospheric pressure to remove the inert solvent having a reflux temperature be dichlorbenzene, and the portion containing the tween about 160° and about 200° C. and passing maleanil was isolated by fractional distillation 15 through the mixture a stream of air containing in vacuo, as described in Example 1. The yield in vapor phase a reagent of the class of volatile, of maleanil was 30 parts. chlorides and bromides the formulae of which Example 5.—-This example illustrates the use are derived by substituting at least one of the of an acidyl bromide in place of an acidyl chlo OH groups of organic and inorganic acids by ride. 20 a halogen of the group consisting of chlorine In a suitable apparatus ?tted with a re?ux and bromine, while re?uxing the mixture so as condenser and agitator, 98 parts of maleic an to maintain the mixture at a temperature be hydride were dissolved in 650 parts of commer tween about 160° and about 200° C. and so as cial ortho~dichlorbenzene. The solution was to expel hydrogen chloride or bromide substan rapidly agitated and 93 parts of aniline were tially as formed therein. slowly added. The resulting slurry of maleanilic 6. The process of making a maleanil, which acid was heated to its re?uxing temperature comprises introducing a stream of air containing (about 180° C.), and 100 parts of phosphorus thionyl chloride vapor into a solution of a ma— tribromide were added very slowly over a period leanilic acid in hot ortho-dichlorbenzene at sub of about 45 minutes. Re?uxing of the mixture stantially atmospheric pressure and at the same was continued for about two more hours to expel time re?uxing the mixture so as to maintain it substantially all hydrogen bromide. The mix at a temperature between about 160° C. and ture was then cooled to a convenient tempera about 200° C. and so as to expel hydrogen chlo ture (e. g., between about 10° and 50° C.) and ride substantially as formed. ?ltered to remove insoluble impurities such as ' 7. The process of making a maleanil, which the phenyl aspartate. The clear ?ltrate was comprises introducing a stream of air containing washed successively with water, a dilute aqueous thionyl chloride vapor into a solution of a ma sodium carbonate solution (between 5% and 10% leanilic acid in hot ortho-dichlorbenzene at sub strength), and again with water. The neutral stantially atmospheric pressure and at the same wet oil was separated, and distilled under at time re?uxing the mixture so as to maintain mospheric pressure to remove most of the di it at a temperature between about 160° C. and chlorbenzene. about 200° C. and so as to expel hydrogen chlo The residue was then distilled in vacuo. The ride substantially as formed, subsequently dis fraction distilling at 4 mm. pressure between 138° tilling off the bulk of the ortho-dichlorbenzene and 148° C. was collected separately as crude at about atmospheric pressure, and separating maleanil, and was found to be substantially the the maleanil from the residue by fractional dis same as that obtained in Examples 1 and 4. tillation in vacuo. The yield of crude maleanil was 85 parts. 8. The process of making a maleanil, which Having described several embodiments of my comprises introducing a stream of air containing invention, but without any intent to be limited * thionyl chloride vapor into a solution of a ma thereto, as various modi?cations and alternatives leanilic acid in hot ortho-dichlorbenzene at sub will be evident to those skilled in the art, what stantially atmospheric pressure and at the same I claim is as follows: time re?uxing the mixture so as to maintain 1. A process of making maleanils comprising it at a temperature between about 160° C. and treating a maleanilic acid at a temperature of about 200° C. and so as to expel hydrogen chlo about 160-200° C. with a reagent of the class of ride substantially as formed, subsequently, dis chlorides and bromides the formulae of which tilling off the bulk of the ortho-dichlorbenzene are derived by substituting at least one of the at about atmospheric pressure, separating the OH groups of organic and inorganic acids by a maleanil from the residue by fractional distilla halogen of the group consisting of chlorine and tion in vacuo, and purifying the crude maleanil bromine. by fractional crystallization. 2. A process of converting a maleanilic acid JOHN H. SPEER. into the corresponding maleanil, comprising