Patented Dec. 23, 1947 2432,991

UNITED STATES PATENT OFFICE

ACYLATION OF THOPHENE Howard D. Hartough, Pitman, and John J. Sar della, Woodbury, N. J., assigners to Socony Wacuum Oil Company, incorporated, a corpo ration of New York No Drawing. Application January 8, 1946, Seria No. 642.13 12 Claims, (C. 260-329) 2 This invention relates to a catalytic acylation in carbon disulfide to a suspension of aluminum process for thiophenes and, more particularly, is chloride in the same solvent. If, however, a car directed to a method for acylating thiophene and oon disulfide solution of the acid chloride was its derivatives in the presence of glauconite as a added to a suspension of thiophene and alumi catalyst. r nun chloride, much tar was formed and a low The acylation of thiophene. and thiophene de yield of ketone resulted. The acylation of thio rivatives has previously been carried out employ phene has, accordingly, been an exceedingly dif ing Organic acid anhydrides, acyl halides, and fictly reaction to carry out, the usual acylation acyl nitriles as acylating agents and in the pres catalysts causing excessive resinification of the eace of various catalysts, including aluminun thiophene reactant. The resinification usually chloride, stannic chloride, titanium tetrachloride, occurs before acylation can be effected, and if phosphorus pentoxide and 2-chloronercurithio 'the expected reaction product is formed, it is phene. Other methodis of inaking acylated thio generally only in relatively Small amounts. phene include the dry distillation of calcium It has now been discovered that acylated thio salts of thiophene carboxylic acids and the action s phenes may be obtained in an efficient manner of nitriles on thienyiragnesium iodide. by reacting thiophene or thiophene derivatives Of these processes, the catalytic methods en with an acylating agent in the presence of a Small ploying Friedel-Crafts type catalyst, such as alus amount of glauconite. It has been found that by inum chloride, stannic chloride, titanium tetra using glauconite as a catalyst, the above-men chloride and the like, have been used most ex tioned difficulties encountered in the acylation of tensively. These catalysts, although applicable thiophene have largely been overcome. Thus, by with considerable Success in the acylation of aro employing a catalyst of glauconite, the undue re ratic hydrocarbons, are only moderately Success sinification and formation of addition complexes fu where thiophene is involved. This appears formerly encountered in the catalytic acylation to be due to the relative instability of the thio ES of thiophene have been substantially eliminated, phene ring; the Friedel-Crafts catalyst, for exam the products resulting being almost entirely acyl pe aluminum chloride, attacking the sulfur and thiophenes having one or more side chains corre causing many undesirable secondary reactions sponding to that of the acylating agent, it has with concomitantly low yields of acy thiophenes, been found, in accordance with this invention, Furthermore, compounds such as aluminum chlo that glauconite effects the acylation of thiophene ride form addition complexes with the carbonyl smoothly and specifically in contrast to the more group of the resulting ketone, Substantially de conventional catalysts employed heretofore, giv creasing the yield of desired product and requir ing a substantial yield of desired ketone without ing a considerable excess of aluminum chloride accompanying formation of complex addition over the theoretical amount required for the products and resinification. The acylation of acylation process. Thus, when aluminum chlo thiophenes using glauconite as a catalyst, more ride is used as the condensing agent, the mole over, can be carried out in a direct manner with ratio of catalyst to acyl chloride or acyl nitrile out a detailed observance of experimental con is at least one and, in the case of acid anhydrides, ditions, such as is a necessary precaution to be at least two. Likewise, other Friedel-Crafts cat 40 taken when aluminum chloride is employed as alysts, such as stannic chloride, must be used in catalyst. molecular quantities with respect to the acyl hal It is, accordingly, an object of the present in ide being employed in the acylation of thiophene. vention to provide an efficient process for Syn This is probably due to the fact that acyl halides thesizing acylated thiophenes. Another obiect is form comparatively stable molecular complexes 5 to provide a process for catalytically acylating with aluminum chloride and stannic chloride, thereby diminishing their catalytic effect. thiophene and its derivatives. A still further ob Moreover, the use of aluminum chloride in the ject is to afford a process for catalytically acyl acylation of thiophene entails strict observance ating thiophene in a relatively simple and direct of detail in experimental observations. Thus, it 50 manner which can be easily carried out by using is known that thiophene and aluminum chloride an inexpensive, easily obtainable catalyst. A react vigorously in carbon disulfide suspension, very important object is to provide a process ca It has been reported that a moderately good pable of reacting thiophene or its derivatives with yield of phenylthienyl ketone is obtained by add an acylating agent in the presence of an efficient ing a solution of benzoyl chloride and thiophene 55 catalyst without undue formation of addition 2,482,991 3 complexes between the catalyst and thiophene or Thiophene or derivatives of thiophene having between the catalyst and acylating agent. one or more substituent groups, such as halogen, These and other objects which will be recog alkyl, aryl, or alkoxy groups attached to the thio nized by those skilled in the art are attained in phene ring, may be acylated in accordance with . accordance with the present invention, wherein this invention. The 2- and 5-positions in the thiophene or its derivatives are acylated by reac thiophene ring, being adjacent to the sulfur atom, tion with organic carboxylic acid anhydrides or are generally much more reactive than the 3- and acyl halides in the presence of glauconite as a 4-positions and, in acylating thiophene, the en catalyst. tering acyl group will preferably attach itself to Glauconite, also referred to as greensand, is 10 the carbon atom adjacent to the sulfur. When the well known to the art as a water softener wherein 2-position of the thiophene ring is already occupied it plays the role of an ion exchanger. It is a by a substituent group or atom, the entering acyl naturally occurring deposit found in various lo group will preferably attach itself to the 5-posi calities. Its exact composition, of course, will be tion. When the 3-position is occupied, the acyl dependent upon the area in which it is found. 15 substituent will enter for the most part at the 2 In general, the oxides of aluminum, silicon, iron, position. However, in some instances, a small potassium and magnesium will comprise the portion of the 3,5-product may be obtained. larger portion of the composition of glauconite Thiophene derivatives having substituents of a employed in the process of the present invention. highly negative character, such as carbonyl, The use of sands containing major amounts of 20 ester, nitro and cyano groups, and no activating the alkaline earth metals such as calcium should substituent, such as a hydroxy or alkoxy group, be avoided, since samples containing relatively do not acylate readily. These groups, commonly large quantities of calcium have been found to referred to as meta-directing, possess a highly have little catalytic effect in promoting the acyl electronegative character which tends to inhibit ation of thiophene. The composition of glau 25 the acylation reaction. conite may generally be defined as follows: The acylation of thiophene or its derivatives is carried out, in accordance with the process of this Per cent invention, by employing substantially equimolar - composition quantities of thiophene and acylating agent. An SiO2 ------40.00 to 53.61 30 excess of either of the reactants, as will be shown Alao.3 ------6.62 to 13.00 hereinafter, does not appear to appreciably affect FeaC3 ------15.16 to 23.43 the yield of acylated thiophene. The upper limit Fe0 ------1.32 to 10.17 of temperature at which the process is carried out MgO ------0.95 to 2.97 will be dependent upon the boiling point of the re Cao ------0.57 to 1.97 35 actants at the specific pressure of the reaction. Na2O ------0.42 to 2.6 In general, temperatures between about 80° C. K2O ------3.49 to 9.54 and about 150° C. and pressures between atmos HoO ------4.93 to 10.32 pheric and about six atmospheres have been It may be used in accordance with the present found satisfactory for effecting the acylation re invention upon mere drying to remove adhering 40 action. The effect of increased pressure, theo surface water or may be activated by acid treat retically, is toward increased reaction but, from ment and heating at an elevated temperature. a practical standpoint, this is not a very great A catalyst which had been activated by the latter effect with reactions such as those involved here treatment was found to give a higher yield of in, which go readily at normal pressures. The acylated thiophene. Glauconite is employed in temperature to be employed will depend on the the process of this invention in a finely divided time of reaction and the nature of the acylating form and in amounts between about 4 and about agent used. Ordinarily, a pressure sufficient to 25 per cent, based on the weight of the reactants. maintain the reactants in the liquid phase is emi The acylating agents to be used herein may be ployed and this is more or less dependent upon 50 the particular temperature involved. As a gen an organic carboxylic acid or an acyl, halide. eral rule, the higher the temperature, the higher Included in the former category are compounds the pressure and the lower the reaction time that such as the ketenes, having the basic structure may be needed. It is, of course, to be understood that these reaction variables are more or less in 55 terdependent. Under the conditions encountered and which yield carboxylic acids upon contact in the process of this invention, however, the re with water. These acylating agents may be de action period will generally vary from about 1 to rived by methods well known to the art from about 10 hours. - mono or dibasic organic acids which may be Acylated thiophenes produced in accordance either unsaturated or saturated. Thus, repre 80 with this invention are useful as solvents, dye in sentative acylating agents to be used in this in termediates, addition agents for petroleum frac vention include the anhydrides of saturated fatty tions, plasticizers, odorants, perfume diluents, acids, such as acetic anhydride, propionic an resin intermediates and intermediates for chemi hydride, ketene, etc.; the acyl halides of saturated cal synthesis. Long chain alkyl thienyl ketones fatty acids, such as acetyl chloride, stearyl chlo 65 may also find uses.as synthetic lubricants, waxes, ride, etc.; the acyl halides of dibasic acids, such extreme pressure additives for mineral oils and as phthalyl chloride; the anhydrides of unsatu anti-foaming agents. rated acids, such as crotonic anhydride; and the The following examples will serve to illustrate acyl halides of unsaturated acids, such as crotonyl the process of this invention without limiting the chloride. These acylating agents are given merely 70 Sale: by way of examples and are not to be construed as Eacample 1 limiting, since other acyl halides or anhydrides of carboxylic acids which will readily suggest them To a mixture of 84 grams (1 mole) of thiophene Selves to those skilled in the art may likewise be and 107 grams (1 mole) of 95% acetic anhydride employed. 75 were added 25 grams of raw glauconite previously 9,482,991 5. dried at 100° C. to remove surface water. The Ecample 5 mixture was heated to a reflux for a period of 5 To a mixture of 84 grams (1 mole) of thiophene hours, the temperature progressively rising from and 107 grams (1 mole) of 95 per cent acetican 104° to 124° C. At the end of this time, the reac hydride were added 50 grams of raw, dried glau tion mixture was cooled and the glauconite re conite. The reaction procedure of Example 1 was moved by filtration. The catalyst was washed followed and 92 grams of 2-acetylthiophene, rep with 50 milliliters of chloroform and the result resenting a 73 per cent conversion, were obtained. ant washings and filtrate were transferred to a still where chloroform, unreacted thiophene, Eacample 6 acetic acid, and unreacted acetic anhydride were 10 distilled off at atmospheric pressure. The still To a mixture of 84 grams (1 mole) of thiophene was then placed under vacuum and 57 grams of and 107 grams (1 mole) of 95 per cent acetican 2-acetylthiophene, having a boiling point of 85 hydride were added 25 grams of activated glau 88° C. at 8 millimeters pressure, were obtained. conite. The activation of glauconite was carried This represents a 45 per cent conversion to the 15 out by treating 589 parts by weight of dried glau ketone. conite with 1800 parts by weight of distilled wa Eacample 2 ter, 120 parts by weight of concentrated sulfuric acid and 120 parts by Weight of ferrous sulfate, To a mixture of 84 grams (1 mole) of thiophene and agitating the mixture at 80° C. for five hours. and 321 grams (3 moles) of 95 per cent acetic an 20 The mixture at the end of this period was allowed hydride were added 20 grams of raw glauconite to settle and the water layer decanted. The cata previously dried at 100° C. to remove surface wa alyst was then stirred with water, transferred to a ter. The mixture was heated to a reflux over a filter and washed with distilled Water until the fill period of 44 hours, the temperature progressive trate was free of acid. ly rising from 115° C. to 128° C. The reaction 25 The mixture of thiophene, acetic anhydride, mixture was then cooled and the glauconite re and activated glauconite was refluxed for 5 hours, moved by filtration. The catalyst was washed the temperature progressively rising from 105 C. with iO0 milliliters of chloroform. The result to 123° C. The reaction mixture was then treated ant washings and filtrate were transferred to a as in Example 1 and 82 grams (66 per cent con still Where chloroform, unreacted thiophene, 30 version) of 2-acetylthiophene were obtained. acetic acid, and unreacted acetic anhydride were From the above examples, it will be evident removed in order at atmospheric pressure. The that glauconite, either in its naturally occurring state or activated by acid treatment, is an effec still was then placed under vacuum and 63 grams tive, inexpensive catalyst for promoting the acyl of 2-8cetylthiophene were obtained upon distill ation of thiophenes. In the light of the prior art, lation. This represents a 50 per cent conversion the present invention is to be given a broad in to the ketone. terpretation and is not to be unduly limited ex Eacample 3 cept as hereinafter defined by the appended claims. To a mixture of 252 grams (3 moles) of thio We cairn: phene and 107 grams ( mole) of 95 per cent 1. A process for nuclear acylation of a thios acetic anhydride were added 20 grams of raw, phene comprising reacting a thiophene with an dried glauconite. The mixture was heated to re acylating agent selected from the group con fux over a period of 6 hours, the temperature sisting of acyl halides and anhydrides of car progressively rising from 87° C. to 95° C. The re boxylic acids in the presence of glauconite as a action mixture was then cooled and the glau catalyst. conite removed by filtration. The catalyst was 2. A process for nuclear acylation of a thio Washed with chloroform and the washings and phene comprising reacting a thiophene with an filtrate were distilled, yielding 63 grams of 2 acylating agent selected from the group con acetylthiophene. This represents a 50 per cent 50 sisting of acyl halides and anhydrides of car conversion to the ketOne. boxylic acids in the presence of naturally occur ring glauconite as a catalyst. Eacample 4 3. A process for nuclear acylation of a thio To a mixture of 168 grams of thiophene (2 phene comprising reacting a thiophene with an moles) and 140 grams of benzoyl chloride (1 55 acylating agent selected from the group consisting mole) were added 20 grams of raw, dried glauco of acyl halides and anhydrides of carboxylic acids nite. The mixture was heated to reflux over a in the presence of an activated glauconite as a period of 44 hours, the temperature progressive catalyst. ly rising from 85 C. to 108.5° C. The reaction 4. A process for nuclear acylation of a thio mixture was then cooled, filtered, and the glau 60 phene comprising reacting a thiophene with an conite Washed with 150 cubic centimeters of ben acylating agent selected from the group consisting Zene. The mixture of resultant washings and fil of acyl halides and anhydrides of carboxylic acids trate was treated with 100 cubic centimeters of 15 in the presence of from about 4 to about 25 per per cent potassium hydroxide solution to neu cent by weight of glauconite. tralize any unreacted benzoyl chloride. The mix 35 5. A process for nuclear acylation of a thio ture was then transferred to a separatory funnel, phene comprising reacting a thiophene with a the potassium hydroxide layer removed, and the carboxylic acid anhydride in the presence of remaining layer was transferred to a steam bath, glauconite as a catalyst. where benzene was evaporated. 177 grams of 6. A process for nuclear acylation of a thio crude product (94 per cent yield) were obtained. 70 phene comprising reacting a thiophene with an The crude product was then vacuum-distilled and acyl halide in the presence of glauconite as a 145 grams of benzothienone, having a boiling catalyst. point of 143-144° C. at 3 millimeters pressure, 7. A process for nuclear acylation of thiophene were obtained. This represents a 77 per cent reacting thiophene with a fatty acid anhydride yield of purified product. 75 in the presence of glauconite as a catalyst. 2,432,991 7 8 8. A process for nuclear acylation of thiophene between about 80 C. and about 150° C. for a reacting thiophene with acetic anhydride in the period of from about 1 to about 10 hours. presence of glauconite as a catalyst. 11. A process for nuclear acylation of a thio 9. A process for nuclear acylation of a thio phene comprising reacting a thiophene with an phene comprising reacting a thiophene with ben acyl halide in the presence of from about 4 to catalyst.zoyl chloride in the presence of glauconite as a about 25 per cent by weight of glauconite. 12. As process for nuclear acylation of a thio 10. A process for nuclear acylation of a thion phene comprising reacting a thiophene with a car phene comprising reacting a thiophene with an boxylic acid anhydride in the presence of from acylating agent selected from the group consisting 0 about 4 to about 25 per cent by weight of glauco of acyl halides and anhydrides of carboxylic acids nite. in the presence of from about 4 to about 25 per cent by weight of glauconite at a temperature HOWARD D. HARTOUGH. JOHN J. SARDELLA,