Patented Dec. 13, 1949 2,490,842 UNITED STATES PATENT of FICE ANSOLE MANUEFACTURE Walter D. Smutz, Bedford, Ohio, assignor to E. I. du Pont de Nemours & Company, Wilmington, Del., a corporation of Delaware No Drawing. Application January 27, 1947, Serial No. 724,718 8 Claims. (C. 260-612) 2 This invention relates to etherification proc contain a plurality of rings, as in the case of esses and more particularly to processes for pro naphthol. There may be a plurality of hydroxy ducing methyl ethers of aromatic hydroxy com groups on the aromatic nucleus, as in the case pounds, especially anisole, in which a methyl of resorcinol. There may be substituent groups sulfate is added to a hot aqueous solution of a . On the ring, as in the case of vanillin. salt selected from the group consisting of alkali The methyl sulfate used according to a proc metal and ammonium salts of aromatic ring ess of this invention may be a sulfate having a substituted hydroxy compounds, the rate of ad methyl group directly attached to the sulfate dition being such that the methyl sulfate does radical. The methyl sulfate may also contain a not exceed its solubility in the solution, whereby 0. metal substituent on the sulfate radical, as in reaction occurs and a methyl ether of the aro the case of sodium methyl sulfate or potassium matic ring-substituted hydroxy compound is methyl sulfate, it may contain an ammonium formed, and the methyl ether is removed from substituent as in the case of ammonium methyl the reaction mixture as fast as it is formed. sulfate, or it may contain a hydrogen substituent Processes for etherifying aromatic hydroxy 15 as in the case of methyl acid sulfate. When compounds heretofore available have Suffered dimethylsulfate is the methyl sulfate used par from the disadvantage that poor yields were ob ticular advantages are achieved, because prob tained based on the amount of etherifying agent lens arising from the sparing solubility of the used. Yields as high as 75% have been consid dimethyl sulfate are overcome according to a ered to be about all that could be expected. Di 20 method of this invention. methylsulfate is often used as an etherifying The methyl Sulfate is added to an aqueous so agent and the poor yields obtained have been lution of a salt selected from the group consist explained on the premise that the first methyl ing of alkali metal and ammonium salts of the group is readily available for reaction and is aromatic ring-substituted hydroxy compound. readily converted but the second group is tena 2 5. Thus, the Solution may, for instance, contain ciously held and that even prolonged exposure Sodium, potassium, lithium, or ammonium of an etherifiable material to the action of di phenate, in which cases the ether formed will methylsulfate would not suffice to increase the be the methyl ether of phenol, anisole. The yield above the 75% maximum. aqueous Solution should remain hot, it being pre Now according to the present invention it has 30 ferred to conduct the reaction at upwards of 80° been found that yields up to almost 100% of C. It is particularly preferred to maintain the theoretical may be achieved in proceSSes for temperature at or above that at which the prod producing methyl ethers of aromatic hydroxy uct formed is steam-distilled off as fast as it is compounds by adding a methyl sulfate to a hot formed. In the case of anisole, for instance, this aqueous solution of a salt selected from the group temperature is about 106° C. consisting of alkali metal and ammonium salts It is desirable that the aqueous solution con of aromatic ring-substituted hydroxy compounds, tain a Substantial concentration of the salt of the rate of addition being such that the methyl the aromatic hydroxy compound. Particularly sulfate does not exceed its solubility in the Solu beneficial results are obtained when the concen tion, whereby reaction occurs and a methyl ether 40 tration is above about 12% by Weight of the salt of the aromatic ring-substituted hydroxy com and in the case of the manufacture of anisole pound is formed, and removing the methyl ether it is especially preferred that the solution con from the reaction mixture as fast as it is formed. tain about 23% of sodium phenate by weight. The invention will be particularly described The rate of addition of the methyl sulfate with relation to processes for producing anisole, 45 should be such that it does not exceed its solu C6H5OCH3 using dimethylsulfate as the methylat bility in the solution. When a metal methyl ing agent but it will be understood that the proc Sulfate or ammonium methyl sulfate is used the esses are applicable to the production of methyl solubility is relatively high and the rate of ad ethers of other aromatic hydroxy compounds and dition may be relatively rapid at least until the that methyl acid Sulfate may be used as the 50 Solution becomes partially saturated with the methylating agent, metal Sulfate formed by the reaction. A com By the term “aromatic hydroxy compound' is mon ion effect then occurs and the rate of addi meant any compound in Which there is a hy tion may need to be reduced. When methyl acid droxy group attached directly to an aromatic sulfate is used it may be desirable to have pres ring, such as phenol. The aromatic nucleus may 55 ent in the reaction mixture an amount of a basic 2,490,842 3 4 material sufficient to react with the acid sulfate ing-out procedure is nevertheless ordinarily eco radical. On the other hand, when dimethylsul nomically justified. fate is used the rate of addition will need to be In practice all of the foregoing operation steps relatively slow because dimethyl sulfate is only may advantageously be carried out continuously. Sparingly soluble in the reaction medium. In the case of anisole, for instance, the Sodium It is particularly preferred that the reaction phenate may be continuously formed in the re mixture be violently agitated during the addi action mixture by adding phenol and sodium hy tion of the dimethylsulfate and that the dimeth droxide in stoichiometric proportions. A slight yisulfate be added to the bottom of a volume of excess of Sodium hydroxide may be used here in the aqueous Sodium phenate solution. The di O the event that the dimethylsulfate to be used methylsulfate may be run in, for instance, through should contain free sulfuric acid. Steam distill an addition tube extending to the bottom of the lation of anisole, the separation of anisole and reaction tank and an agitator may be so disposed water from the distiliate, the removal of sodium as to create an intense Zone of agitation at the sulfate, and the Saturation of the distillate with end of this addition tube. It will be understood s the Sodium sulfate may all be carried out con that even though the Solution is not saturated tinuously with the operational advantages which with respect to dimethylsulfate the undesirable Such operation entails. condition of having undissolved dimethylsulfate The nature of this invention will be better may nevertheless result unless care is taken to understood by reference to the following illustra disperse the dimethylsulfate as it enters the re 20 tive examples. action mixture. Under the conditions above described a reac Eacample 1 tion occurs and a methyl ether of the aromatic To a reaction vessel there was added 67.2 parts ring-Substituted hydroxy compound is formed. by weight of water and 23 parts by weight of The reaction of dimethylsulfate and Sodium 25 phenol and the mixture was heated with agita phenate, for instance, proceeds according to the tion to 50° C., whereupon the phenol melted and following equation: Went into Solution. There was then added 9.8 parts by weight of sodium hydroxide pellets and 30 the mixture was stirred until the sodium hy It will be noted that this equation calls for the droxide dissolved, whereby reaction occurred and use of both of the methyl groups on the dimethyl sodium phenate was formed. This gave 100 parts Sulfate and the processes of the present invention by weight of a 28.4% sodium phenate solution. accomplish substantially this result. Heretofore This Solution was heated to 112° C., which was it has been regarded as impossible to recover more 35 approximately its boiling point. To the solution than about half of the second methyl group in there was then added, simultaneously, dimethyl the product. Sulfate and a Sodium phenate solution containing As fast as the methyl ether of the aromatic 21% by weight of Sodium phenate and .05% of ring-substituted hydroxy compound is formed it Sodium hydroxide. The purpose of the sodium should be removed from the reaction mixture. 40 hydroxide was to neutralize an equivalent free Where the conditions are right, as in the case of acidity in the dimethylsulfate. The dimethylsul anisole, this may ideally be accomplished by Steam fate was added through an addition tube extend distillation, that is, by carrying out the reaction ing to the bottom of the reaction vessel and the at a temperature Sufficiently high to effectuate reaction mixture was violently agitated, with the steam distillation of the product. The distillate 45 Zone of maximum agitation being at the point may then be condensed, separated as by gravita of delivery of the dimethylsulfate. The dimethyl tion into an anisole layer and an aqueous layer, Sulfate and additional sodium phenate solution and the aqueous layer returned to the reaction Were charged in gradually over a period of two mixture. Preferably the portion of aqueous layer hours. During the addition care was exercised to which is returned to the reaction mixture should 50 avoid adding dimethylsulfate at a high enough be taken from a point proximate to the anisole rate to exceed its solubility in the reaction mix aqueous interface because any anisole entrained ture, that is, no undissolved dimethylsulfate was in the aqueous fraction is thereby recovered. It permitted to be present. will be apparent, of course, that not all of the It was noted that upon addition of the dimeth aqueous fraction will need to be returned, but only 55 ylsulfate and Sodium phenate solution the tem that portion required to maintain the volume of perature of the mother liquor dropped from the reaction mixture substantially constant. 112 C. to 106° C. and there was immediately It will be observed from the above equation that formed a cloud in a distillation column connected sodium sulfate is a by-product of the reaction. with the reaction vessel indicating the formation This may be removed by allowing it to accumulate 60 of an anisole water vapor mixture. The tem until it exceeds its solubility and crystals are perature was maintained so that the anisole formed, the crystals being withdrawn by allowing Steam-distilled off as fast as it was formed. The them to settle out and withdrawing them through distillate was collected and allowed to separate a device Such as a salt-lock. Alternatively the re gravitationally into 2 layers. The lighter layer action mixture may continuously be withdrawn, 5 was withdrawn as product. It was found to be passed through a screen to remove the crystals, anisole of high quality. and the clarified mixture returned to the reaction The rate of dimethylsulfate addition was such vessel. In either case the crystals may be washed, that it did not exceed the rate of distillation of as with water, to avoid carry-out losses. anisole, that is, for each unit volume of dimethyl The washed crystals may be redissolved in the 70 sulfate added 2.3 volumes of anisole were dis aqueous fraction of the steam distillate, if de tilled Over. sired, to give a salting-out effect whereby the re It was noted that during the course of the covery of the aromatic ether is improved. While reaction sodium sulfate was formed and even anisole, for instance, has a very low solubility in tually exceeded its solubility so that it was present water the improvement effected by such a salt 75 in Solid form in the reaction mixture, 2,490,842. 5 6 An over-all yield of 93.6% of anisole was ob The cone bottom of the reactor is connected to tained, based on the total dimethylsulfate an inclined pipe in which is located a conveyor. charged. It should be observed, however, that screw adapted for advancing precipitated sodium after-half of the dimethylsulfate had been added sulfate up the incline to a point above the liquid the agitation was increased in intensity and the 5 level in the reactor tank and ultimately discharg yield for the last half of the addition was 98.5%. ing a drained sodium sulfate crystal. Provision It is further. to be noted that after addition of is made in the inclined pipe to wash the crystals the dimethylsulfate was completed Steam dis with Water from the above-mentioned gravi tillation was continued until a total of 80 parts metric separator. by volume of additional distillate were collected. 10 In carrying out the reaction in the above Of this volume only 12 parts was found to be described apparatus Sodium hydroxide and anisole, indicating that the anisole was steam phenol are added through their respective addi distilling out.practically as fast as formed. . tion inlets in stoichiometric proportions until a Eacample 2 predetermined volume of sodium phenate is 5 formed in the reactor. The sodium hydroxide is In this embodiment of the invention the methyl added in the form of a 50% aqueous solution and sulfate employed is methyl acid sulfate, Sufficient water to provide turbulent flow in the CH3HSO4. The procedure of Example 1 is re reaction arm is provided. Sufficient water is peated exactly except that instead of dimethyl added to the reactor to bring the level up to a sulfate there is added methyl acid sulfate and predetermined maximum whereby a solution con at the same time there is separately added an taining at least 23% of sodium phenate is pro amount of sodium hydroxide Stoichiometrically duced. Heat is then supplied through the heat equivalent to the acidity of the methyl acid Sul exchanger sufficient to bring the entire volume fate. In this way the heat of neutralization of of solution up to 112 C. Addition of dimethyl the methyl acid sulfate-sodium hydroxide re 2 5 Sulfate is started and addition of sodium hy action is formed in the reaction mixture and droxide and phenol is continued, the proportions less added heat needs to be furnished. of these reactants being stoichiometrically equiv By this method anisole of high purity and in alent with sufficient excess sodium hydroxide to good yield is obtained. avoid any build-up of acidity from the dimethyl 30 Sulfate. The Solution returning to the reactor Eacample 3 from the heat exchanger contains anisole which A continuous process for making anisole con at a temperature of 112° C. tends to steam dis tinuously on semi-works scale is described as foll till off. This tendency is restricted, as by means lows: of an orifice, until the solution enters the upper 5 portion of the reactor. There it is permitted to - The equipment in this embodiment of the in flash distill, the anisole and water vapor passing vention comprises a cone bottom reactor of such to the condenser, thence to the gravimetric sep a size that the surface vapor velocity does not arator, and the anisole product is withdrawn exceed 20 pounds per square foot per hour and Water is returned to the reactor. The flash evaporation rate at atmospheric pressure, the t distillation effects a drop in temperature to about tank being about 2 feet in diameter. The tank is 106° C. and additional heat is supplied from the a closed vessel having a side outlet consisting heat exchanger continuously to bring the tem of a 14' O. D. pipe 4 feet long connected with perature up to 112 C. After the process has a centrifugal pump, the discharge side of which been in operation for a time sodium sulfate be is connected through a heat exchanger to a re 45 gins to crystallize out in the reactor. A portion turn pipe which opens into the reactor above the of this sodium sulfate continuously settles in the liquid level in the reactor. The centrifugal pump cone bottom of the reactor and is continuously has a capacity sufficient to produce turbulent withdrawn through the inclined pipe by means flow throughout the outlet, heat eXchange, and of the screw conveyor. The crystals are washed return lines to a degree sufficient to prevent 50 as they are withdrawn by means of a counter deposition of sodium sulfate on the pipe walls current Wash using water from the gravimetric within the heat exchanger. As close as possible Separator. to the point where the outlet pipe leaves the reactor are located first, an inlet for Sodium It is seen that the foregoing process provides hydroxide solution and second, an inlet for a continuous operation for making anisole. The phenol. As close as possible to the point where 55 yields are very satisfactory being in all cases this pipe delivers into the pump is located an in upwards of 93% and under preferred conditions let for dimethylsulfate. The turbulence within being 98% or better, based on the dimethylsul the tube is sufficient to give instantaneous mix fate used. - - ing of sodium hydroxide, phenol and dimethyl sulfate, and additional intense agitation is pro 60 Eacomple 4 vided by the shearing action within the centrifu This example describes the application of a, gal pump. The heat exchanger has sufficient process of this invention to the production of heat exchange capacity to cause vaporization of Veratraldehyde from vanillin. the anisole and a quantity of water sufficient to 65 steam distill it as soon as the solution is returned The apparatus used in this example is similar to the reactor. to that of Example 3 except that the condenser From the top of the reactor a gas vapor pas and gravimetric separator are eliminated and sage connects to a condenser, the product dis the reactor is provided with means for removing charge passage from which connects to a gravi 70 molten veratraldehyde from a stagnant pool at metric separator. At the top of this separator is the top of the liquid level. a product discharge outlet and at the bottom is The reaction involved consists in treating van a water discharge outlet leading back to the illin with sodium hydroxide to form sodium van reactor through an overflow box with means for illate and methylating the sodium vanillate to maintaining a constant level in the reactor. veratraldehyde according to the equations: 2,490,842: 8. at a "temperature high enough to steam-distill vanilin sodium vanilate anisole but not substantially higher, the rate of 1. H-C-O H-C=O addition being Such that the dimethylsulfate does not exceed its solubility in the solution, whereby - NaOH - - HO reaction occurs forming anisole and Sodium Sul OCE OCH fate, as fast as anisole is formed steam-distilling OE ON, it off, condensing the distillate, separating it into (Soluble) an anisole fraction and an aqueous fraction, and 2. withdrawing the anisole fraction as product. -Cs. O H-C-O O 5. In a process for producing anisole, the steps CH3 Comprising continuously adding dinnethylsulfate N 2 -- SO - 2 -- Na2SO4. with violent agitation to the bottom of a volume OCH. cf. OCI of an aqueous Solution, containing about 23 per cent of sodium phenate by Weight at about 106 Na OCH C. under about One atmosphere absolute pressure The vanillin and sodium hydroxide are first in a reaction vessel, the rate of addition being caused to react until a substantial concentra such that the dimethylsulfate does not exceed its tion of Sodium vanillate is achieved in the circu solubility in the Solution, whereby reaction occurs lating reaction solution and the addition of forming anisole and Sodium Sulfate, as fast as dimethylsulfate is then started. Heat is sup anisole is formed steam-distilling it off, condens plied from the heat exchanger to bring the tem ing the distillate, Separating it into an anisole perature up to about 80° C. In this case how fraction and an aqueous fraction, and withdraw ever, the product formed is veratraldehyde which ing the anisole fraction as product. is not sufficiently volatile to make Steam dis 6. In a process for producing anisole, the steps tillation practicable. Therefore the reactor is comprising. Continuously adding dimethylsulfate so constructed that opportunity for gravimetric with violent agitation to the bottom of a volume separation is provided, the Veratraldehyde col of an aqueous Solution Containing about 23 per lecting as a molten, insoluble liquid at the top of cent of Sodiumphenate by weight at about 106 the liquid in the reactor. From this collection C. under about one atmosphere absolute pres point the veratraldehyde is drawn off continu 30 Sure in a reaction vessel, the rate of addition ously as product, being such that the dimethylsulfate does not ex By the foregoing process veratraldehhyde is ceed its solubility in the solution, whereby re continuously produced and in good yield. action occurs forming anisole and sodium sulfate, as fast as anisole is formed Steam-distiling it ... I claim: 35 off, condensing the distilate, separating it into i. In a process for producing anisole the steps an anisole fraction and an aqueous fraction, comprising adding a methyl sulfate with agita withdrawing the anisole fraction as product, re tion to a hot aqueous solution containing more turning to the reaction vessel aqueous fraction than about 12% by weight of a phenate Selected aS required to maintain the Volume of reaction from the group consisting of alkali metal phe 40 mixture. Substantially constant, and removing nates and ammonium phenate at a rate Such that SGdium Sulfate as crystals from the reaction the methyl sulfate does not exceed its Solubility mixture. in the solution, whereby reaction occurs to form 7. In a proceSS for producing anisole, the steps anisole, and removing the anisole from the re comprising continuously adding dimethylsulfate action mixture as fast as it is formed. with violent agitation to the bottom of a volume 2. In a process for producing anisole, the steps of an aqueous Solution containing about 23 per comprising continuously adding dimethylsulfate cent of SOdium phenate by weight at about 106 with agitation to an aqueous solution containing C. under about one atmosphere absolute pres more than about 12 per cent of Sodium phenate Sure in a reaction vessel, the rate of addition be by weight at a temperature high enough to 50 ing such that the dimethylsulfate does not ex steam-distill anisole but not substantially higher, ceed its solubility in the solution, whereby re the rate of addition being such that the dimethyl action occurs forming anisole and sodium sulfate, sulfate does not exceed its solubility in the as fast as anisole is formed steam-distilling it off, solution, whereby reaction occurs forming an Condensing the distillate, separating it into an isole, as fast as anisole is formed steam-distilling 55 anisole fraction and an aqueous fraction, with it off, and recovering anisole from the material drawing the anisole fraction as product, return so distilled. ing to the reaction vessel aqueous fraction from 3. In a process for producing anisole, the steps a point proximate to the anisole-aqueous inter comprising continuously adding dimethylsulfate face as required to maintain the volume of re with agitation to an aqueous solution containing 60 action mixture substantially constant, and re more than about 12 per cent of sodium phenate moving. Sodium Sulfate as crystals from the re by weight at a temperature high enough to action mixture. steam-distill anisole but not substantially higher, 8. In a process for producing anisole, the steps the rate of addition being such that the dinnethyl comprising continuously adding dimethylsulfate sulfate does not exceed its Solubility in the With violent agitation to the bottom of a volume solution, whereby reaction occurs forming ani of an aqueous Solution containing about 23 per sole, as fast as anisole is formed steam-distilling cent of Sodium phenate by weight at about 106 it off, condensing the distillate, separating it into C. under about one atmosphere absolute pres an anisole fraction and an aqueous fraction, and Sure. in a reaction vessel, the rate of addition withdrawing the anisole fraction as product. 70 being Such that.the dimethylsulfate does not ex 4. In a-process for producing anisole, the steps ceed its Solubility. in the solution, whereby re comprising continuously adding dimethylsulfate action occurs forming anisole and sodium sul with violent agitation to the botton of a Volume fate, as fast as anisole is formed steam-distill of an aqueous solution containing more than ing it off, condensing the distillate, removing about 12 per cent of sodium phenate by Weight 5 Sodium sulfate as crystals from the reaction mix 2,490,842 9 10 ture, Washing the crystals, dissolving then in REFERENCES CITED the condensed distillate, separating the distillate ... into an anisole fraction and an aqueous sodium s. The following references are of record in the sulfate solution fraction, withdrawing the ani file of this patent: sole fraction as product, and returning to the 5. UNITED STATES PATENTS reaction vessel aqueous fraction from a point x: Number N proximate to the anisolé-aqueous interface as Derek" al. Degas required to maintain the volume of reaction mix- 2305.395 Coleman June 26. 1940 ture substantially constant. nFwww.s/W wWawasauvais ------y i. FOREIGN PATENTS WALTER, D. SMUZ. Number Country Date 214,783 Germany ------Oct. 14, 1909