REACTIONS OF COUMALINIC ACID AND PREPARATION OF ITS CHLORIDE BY BENJAMIN WEINPER THESIS FOR THE DEGREE OF BACHELOR OF SCIENCE IN CHEMICAL ENGINEERING COLLEGE OF LIBERAL ARTS AND SCIENCES UNIVERSITY OF ILLINOIS 1922 UNIVERSITY OF ILLINOIS May _ _2 5^_ 1 £12 2_ 1 9 2 THIS IS TO CERTIFY THAT THE THESIS PREPARED UNDER MY SUPERVISION BY ENTITLED 3B£T I.QtLS _ OF.il OUPAL XJ XC_ AC ID_ TI QF_I_TS_CHLORI_DE_. IS APPROVED BY ME AS FULFILLING THIS PART OF THE REQUIREMENTS FOR THE DEGREE OF BMm.PR__0F .SCIEIiCJ I L. Instructor in Charge Approved HEAD OF DEPARTMENT OF Acknowledgement . The author wishes to express his sincere thanks and gratitude to Dr. B.L. Souther for his kind suggestions and helpful encouragement during this work. Table of Contents Pag- Historical 1 Alpha Tyrones r Theoretical 0 Experimental Coumalinie Acid 8 Methyl Coumalinate 1C Methyl - Chi or o -Coumalinate 12 Furane 2:4 Di carboxylic Acid 13 Summary 14 Digitized by the Internet Archive in 2016 https://archive.org/details/reactionsofcoumaOOwein HISTORICAL Alpha Pyrones Alpha pyrones have been prepared h y several general methods. First, by the action of concentrated sulphuric acid on an aldehyde acid or a ketonie acid. For example , ooumal ini c acid (I) was prepared in the following v nner: CHOH CHOHCOOH CHp I COOK CH CH I I COOK OH ri-rr^TT # V HC uHCOOH / \ HC CGUUri -► | KOOC r. oh S / From acetoacetic acid, isodehydracetic acid (IV) was obtained and in a. similar manner ace tonedi carboxylic acid gave citra- coumalinic acid (III), Second, by the addition of B-ketonie esters and certain ketones to esters of acetylenic acids. Lesoxy benzoin added to ethyl phenylpropiolate giving 4:5:6 triphenyl alpha pyrone (XV ) . CH 0 C 6 H 5 COCoHc CC 5 H 5 CCOOC 2 H5 CC^Hn J X 'D OG ‘0 - tj V Acetylacetone and benzoylacetone in like manner gave respect- ively 4-phenyl-6-methyl-5-aceto alpha pyrone (XVI ) and 4-phenyl -5 -ben zoy 1-6-methyl alpha pyrone (XVII) or 4:6 di- phenyl-5-acetyl alpha pyrone (jtVIl) . In the latter case the formula of the compound is one of the following! HC A$; 1 1 OC^ ^CCH UL, 6 n 5 * HC ^ juL Hts / 1 I •3 on cc 6 h 5 * See table for references. 1 I The following equation expresses the reaction "between ethyl acetoacetate and ethyl phenylpropiolate , = _|_ COOCpH^ „ l •COCH3 COOC2H5CHCOCH3 r* n rTTr. HCT x fCOOCoKr OC /CCH3 4 - Ethyl -4-phenyl -6 -methyl alpha pyrone 5-carhoxylate (XVITl) , The halogen derivatives of the alpha pyrone compounds were obtained by direct chlorination or bromination of the acids and esters. In some instances , as for example, in carrying out the chlorination of methyl counalinate, solvents were used such a.s carbon tetrachloride saturated with chlorine. Coumalin (XIX) the simplest of the alpha pyrones was prepared by H.v Pechmann by the dry distillation of mercurous coumalinate in an atmosphere of hydrogen. o I EC X CCOOH 1 1 0C V J3H C M. P.205-2 10 Soluble in methyl alcohol, acetic acid, ether , water and acetone. Per. 17,2334 II HC^^CH 1 1 OGv CCOOH cr M. P.227-228 Soluble in alcohol, acetic acid, water, and acetone . J.G.S. 1901 T.Pt. 2, 1280 ITT VI CHoCOOH HC X CCOOH 1 II OC. ilCHpCOOH M.P. 185 Turns dark at 150 Soluble in water and alcohol. Annalen 261 190-208 IV >X k 3 HC x C.COOH °G .CCH, N o M.P. 50 Annalen 261 190-202 V (\ TT HG^CCOOSH* 1 1 oa jch M.P. 74 B.P-60 178 - 8 Soluble in ether, alcohol , acetone and water. Annalen 264 271 VI CH HG^ x CGOOC 2 H5 1 II OCv GH C M.P. 36 B. P.262-265 Soluble in ether, alcohol , ace tone and water. Annalen 264 26 1 -309 VII >CH HC X GH 1 II OCv .CCOOCpHc 0 M.P. 59-60 Soluble in water, and in most organic media. J . C . S . 1 90 1 T.Pt. 2 1280 VIII fITT Cl CT 13C00H 1 » °V CH M.P. 187-139 Soluble in acetic acid, alcohol and ether. Ser.37, 3329-36 IX /ITT Gl(/ X CCOOCKj, OC GH M.P. 134-136 Soluble in chloroform, acetone acetic acid, and benzol . Ber. 17, 2396-2399 X Br(X ^CCOOH 1 II °\/ H vj M.P. 17 6 Soluble in ether, alcohol , chloroform and glacial acetic acid Ber. 17, 2396-2399 XI CCH 3 Br”f TICOOH 1 II OC. .CGK 3 x> M.P . 16 1- 162 Soluble in alcohol and benzene. Ber . 26 , 746-747 XII BrC^^COOOCoHc 1 II OC /JCH^ X) M.P. 72 Ber .35, 782-790 XIII n t r ojrl BrC^ XJCOOCoHc 1 1 c v/ :H M.P. 94-95 Soluble in alcohol Annalen 331 367-364 XIV GH HC^ uH l I OC /CC^ TJ M.P. 66-68 Soluble in ether, alcohol, acetic acid and water. Ber . 27, 841-850 4 XV J \ 6 5 Her N cc,qH R 1 1 0C X /CCfiKcj 0 M.P. 245-246 Soluble in glacial acetic acid. Insoluble in water or alcohol. J . G . S . 1 9 1 0 T.457. XVI J$6*5 KCT x C(COGHq) 1 I oc. >gch 3 N o M.P. 128 J.C.S. 1899, T . 4 1 1 . XVII HCT n C(COG5H5] V CH 3 ■ I. P. 143-144 J.C.S. 1899, T . 4 1 1 XVIII HC^' N $C§OC ? He 1 1 °%/ gsh 3 M.P. 104 Ber.35, 782-790 XIX H /%H 1 I C \./" u B.?.2G6-9d l'„T T5 q B^P.30 ' 3 ° Miscible v/ith all ordinary solvents. Annalen 26 4 P.6 1 -309 theoretical Franz Feist treated bromo-isodehydraeetie acid with, potassium hydroxide and obtained a furane derivative. ,0. C CHts BrC^ X CC00H x X 3 -I- /ITT. /t ' ch 3 2:4 dime thy 1 furane - 3 - c ar boxy lie acid He then treated ethyl-bromo-isodehydracetie ester with potassium hvdroxide and obtained a cyclo propene derivative. /CCH 3 BrC^ hCOOC \.x +- L C00HC1I -p CO OH -> CH^cf +- \/ C Ch- ile thy 1-cyclo-propene di carboxylic acid \ TT on methyl-bromo-coumalinate expectng to obte ate a simpler i alpha pyrone to ob tain cy clo-propene from the e thy 1 -bromo= isodehydracetic ester. BrC^ \IC00 CHt5 4 - nun CC X CH 0 4~ \/ Instead he obtained a furane derivative. HO / > J + 3K0H °\/ H — CH,0It + Oil T - T f " : c -h 1 ,0. :ccck COOHC "CCOOH ll CK Furane 2:4 di carboxylic acid. Since methyl-chlorocoumalinate (IX) prepared n-ir o * ' - C* J . J . v.Pechmann and Mills, was never converted either into the cyclo-propene derivative nor into the furane derivative. There existed a curiousity as to which of the two derivatives it would give on treatment with potassium hydroxide, which therefore led to this investigation. 7 EXPERIMENTAL Coumalinic acid: -H.v.Pechmann prepared coumalinic acid (I) "by he* ' Lalie acid (50 grams) t ter bath with a mixture of (75 grams) concentrated sulphuric acid and (75 grams) fuming sulphuric acid containing 10-12 per cent sulphur trioxide, mien the evolution of carbon dioxide ceased in 11/2-2 hours, the solution was carefully mixed with ice (2C0 grams) and kept over night. The Precipitated acid v:r, separated by filtration, ’washed with ice water until almost free from sulphuric acid and then dried on porous piate& * The acid in the mother liquors and washings was extracted by shaking six times with ether. The total yield of tne crude product was about 80 per cent, but it contained funaric acid and traces of trimesic acid. It was purified by dissolving in water between 70-80 degrees, shaking the solution with animal charcoal, and then extracting the acid with ether. It crystallized from from methyl alcohol and glacial acetic acid in colorless prisms, and on heating turned red at 200 degrees, and melted between 2G5~81Q degrees with decompositio ° boiled at 218 degrees under a pressure of 120 mnu.viuh pa; tied. de c ompo s i t i on . As fuming sulphuric acid containing 10-12 per cent sulphur trioxide could not be obtained in tne la^Oi c,uO.. ; > fuming sulphuric acid containing 7 per cent sulphur trioxi-.e was used and the amount per 50 grams of malic acid was calculated. A mixture of (40 grains) concentrated sulphuric • cid and(1l0 grams) of fuming sulphuric acid 7 per cent su_p ' o trioxide was used, and procedure as given by v.Pechmann was carried out. An Cp per cent, yield of crude product was obtained but could not be purified according to v.Pechmann ' s method. Different methods of purification, and such solvents as alcohol, chloroform, acetone, ether, petroleum ether and ethyl acetate were tried but colorless prisms could not be obtained. By dissolving the crude acid in hot glacial acetic acid and allowing it to cool the coumalinic acid crystallized. The crystals had a yellowish color, and no definite shape. The yield of pure acid was 6 3 per cent. Methyl Coumalinate . Methyl coumaliriate ) was prepared hy H.V.Pechmann hy adding to one pa.rt of the acid 2 parts of sulphuric acid and heating for 15 minutes. Then adding one part of methyl alcohol and refluxing for one hour on a water hath . After cooling it was poured into water and filtered to remove fumaric ester and trimesic ester. The filtrate was extracted 12 times with ether, dried, the solution evaporated and the remaining substance crystallized in long needles. It was recrystallized from hot water, ether or ligroin. The yield was 75 to 35 per- cent of the weight of acid used, and the melting point was from 75-74 degrees. Four methods of preparing the ester were tried. ( 1 ) The method used hy H.V.Pechmann; (2) By passing dry hydrogen chloride into a mixture of acid and methyl alcohol; (5) "y treating the silver salt of the acid with methyl iodide; (4) By passing methyl alcohol vapors through a mixture of aci a, sulphuric acid and methyl alcohol. (1) After following v.Pechmann's method of preparation, methyl coumalinate melting from 72-73 degrees was obtained. The best yield obtained in a half dozen trails was 4a per cent of the weight of acid used. (2) One part of the acid was added to one part of methyl alcohol and dry hydrogen chloride was passed in until the solution was completely saturated. . The solution was poured into water and filtered. The filtrate was extracted 12 times with ether, washed with a dilute solution of sodium carbonate ;0 then dried with calcium chloride. The solution was evaporated and a brown sticky substance remained that could not be crystallized. Later it was concluded that if the mass were distilled under diminished pressure methyl coumalinate would be obtained. (3) 10 grams of coumalinic acid was dissolved in ammonia water, made almost neutral with nitric acid and silver nitrate added. The silver salt was filtered off and placed into a flask connected to a reflux condenser. Ether and methyl iodide were added respectively and the solution was permitted to reflux for three hours. After evaporating the ether solution a brown mass remained which could not be crystallized. (4) To 30 grams of coumalinic acid and 6 cc. sulphuric acid,60 cc. of methyl alcohol was e.dded. Absolute methyl alcohol vapors were passed through the mixture removing the water formed in the reaction. TTnen the reaction was complete , the solution was cooled, poured into water and the oil layer was separated from the water layer. The water layer was extracted twelve times with ether, made neutral by washing with a dilute solution of sodium acid carbonate , dried with calcium chloride and the ether evaporated. The resulting material was distilled under diminished pressure. Methyl coumalinate distilled over between 170-130 degrees and -0 mm. Melting point of the ester, 73-74 degrees. The oil layer on distillation gave 6 grams of methyl coumalinate. Total yield of ester was 48 per cent of the weight of acid used. ' Me thy 1 - chi or o c oumalinate To 30 grains of pure methyl coumalinate (30, the calculated amount of carbon tetrachloride saturated with 7-8 per cent chlorine was added and allowed to stand at room temperature. After two or three days hydrogen chloride started to be given off and crystals formed. The crystals were separated, and washed with ether. The crude product (25 grams) was then re crystallized from alcohol. 17 grams of pure chloro-ester melting, 134- 136 degrees was obtained. This method was tried about a dozen times with 5 to 10 grams of pure methyl coumalinate and the best yield obtained was one gram of pure methyl-— chlorocoumalinate for every 10 grams of methyl coumalinate. The crude product obtained melted between 94-103 degrees, but after re crvs tall i zing three times from alcohol, a pure product melting, 133=* 135 degrees was secured. Sulphuryl chloride was tried instead of carbon tetra- chloride but the yield was not increased. ■ I . # Furane 2:4 di carboxylic acid. Meth.yl-bromocoumalin.ate (5grams) were mixed in a cold solution containing (10 grams) potassium hydroxide in (20 grams) of water. It was heated for twenty minutes, allowed to cool and then neutralized with sulphuric acid. The whole mass was placed on a water bath to dry. The brown mass remaining was extracted with acetone. After vaporising the acetone a brown mass remained which was washed with ligroin and recrystallized from hot water. The yield was 3*7 grams , melting at 266 degrees. TIhen 2 grams of methyl-chlorocoumalimate was obtained, the procedure as given above was followed through. The brown mass obtained after vaporizing the acetone was insufficient to carry the operation any further. Lack of time prevented the preparation of more methyl-chlorocoumalinate; thus the problem had to be left without a definite conclusion. * Franz Feist, Ber. 34, 1992-1994. 13 .. - . rt rr«-ir« W ijUiVU'.iiij; lX Coumalinic acid was prepared in better yields than that recorded in the literature. The acid was esterified using sulphuric acid as a catalyst. Difficulty was experienced in preparing methyl- chloro-coumalinate in sufficient quantities to work with. One experiment, methyl-chloro-coumalinate plus potassium hydroxide gave no solid product. 14