Thesis (B.S.)--University of Illinois, 1919.Typescript.Includes bibliographical references (leaf 19)

Gerke, Roscoe H.

English

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THE SYNTHESIS OF COUMARANEDERIVATIVES FROM SALICYLIC ACIDBYROSCOE H. GERKETHESISFor The Degree ofBACHELOR OF SCIENCEIN CHEMICAL ENGINEERINGCOLLEGE OF LIBERAL ARTS AND SCIENCESUNIVERSITY OF ILLINOIS1917UNIVERSITY OF ILLINOISFebruary 24 19P&19THIS IS TO CERTIFY THAT THE THESIS PREPARED UNDER MY SUPERVISION BYROSCOE H. GERKEENTITLED THE Sm.HESIS.._DF . COMARANS DERIVATIVES FROMSALICYLIC ACIDIS APPROVED BY ME AS FULFILLING THIS PART OF THE REQUIREMENTS FOR THEBACHELOR OF SCIENCE IN CHEMICAL ENGINEERINGDEGREE OF.Approved:Instructor in ChargeHEAD OF DEPARTMENT OF.Digitized by the Internet Archivein 2013http://archive.org/details/synthesisofcoumaOOgerkTABIE OF COlITSiJTSTheoretical DiscussionGeneral - -m- -------- Page 3Synthesis of the MethyleneCoumarane of Salicylic Acid - - - - 6Experimental- ---------------- - loAcknowledgements ---------------isBibliography - --------------- 19UlUCTHEORETICAL DISCUSSIONGENSRALUnder the direction of Dr. Roger Adams, a new method for thesynthesis of the alpha methylene derivatives of a class of compoundscalled coumaranes has been developed. These compounds have a fivemembered side ring containing one oxygen atom and are formed by thetreatment of the acetyl derivative of b, r, dibrom ortho allyl phe-nols with alcoholic potash. The experimental work ^ms commenced byMr. Hubert Moor and Mr. Louis Krug. It was continued by Mr. R. E.Rindfusz, who established the mechanism of the reaction and theproof of structure, an exhaustive account of which is included inhis thesis.To determine whether or not the reaction was general for thistype of compoiinds, it waa decided to synthesize methylene coumaraneof salicylic acid. This particular compound was chosen, to deter-mine the effect of the carboxyl and ester group, respectively, onthe reaction; furthermore it was to be expected that these deriva-tives of salicylic acid, if not of its methyl ester, would be solids,which would admit of easier and simpler methods of purificationthan the liquids obtained as derivatives from phenol.Before discussing the coumarane resulting from salicylic acidand its methyl ester, it may be well to briefly discuss the luethodby which Dr. Roger Ad-^ms and Dr. R. E. Rindfusz proved the structureof the methylene coumarane resulting from phenol.5./V //—c—c=»c—//IIO'C- c-//3C-C-Br^II I»Ir\ rrrIcQrIIc-c—//iI\oThe diagram of oompounds shows the mechanism of the reactionsand the proof of structure.The preparation and properties of all^l ether of phenoland ortho allyl phenol have been described . The ortho allylphenol was converted to the acetyl derivative (by means of aceticarJiydride) which on bromination yielded the acetyl derivative ofb, r, dibrom ortho allyl phenol. Upon treating tl.is compound withalcoholic potash, the final com.pound, methylene coumarsne of ben-zene was formed.When the free ortho allyl phenol was brominated a series ofside products were formed. The monobrom ring substituted compoundff£a, 2b, 2c, 2d, see diagram} were both reduced with zinc and hy-drochloric acid and treated with alcoholic potash. In both casesthe residues of the compounds with substituted bromine in thebenzene ring were obtained, but it v/as also found that those thatdid not reduce, did not react with alcoholic potash. These res-idues were, respectively alpha methyl coumarane and the alphamethylene coumarane of brom benzene, (2c and 3a).Alpha monobrom m.ethyl coumarane of benzene, (2d), was pre-pared by treating one mol of the acetyl derivative of dibrom allylphenol with one mol of sodium alcoholate. This was reduced withzinc and hydrochloric acid, yielding saturated alpha methyl coumarane of benzene, whose properties are in entire agreement withthose of the com.poimds containing a five membered ring with oneatom of oxygen V and not with those of the compounds having asix membered ring This monobrom compound was treated withalcoholic potash or with more sodium alcoholate and alpha meth-yleno ooumarane of iDenzene, v/liioh had been synthesized directlyfrom the acetyl derivative of dibrom orthc allyl phenol, v/asobtained.It was expected that the application of this reaction toa derivative of salicylic acid would involve some changes in thenature of the reaction. One would predict that the preparationof the acetyl derivative ortho allyl salicylic acid or its methylester would be more difficult due to steric hindrance; and thatthe bromination should be much cleaner and smoother because thesame phenomenon prevents the reaction from proceeding in the usualmarker in the case of phenols, i. e. that of the bromine reactingwith the phenolic group and then shifting into the para positionin the benzene ring.S-\Tithesis of Methylene Ooumarane of Salicylic// //// H f r fHP f—C—C—C-5.Q//— C—OA// //I I Ic—c=cIOC-OH-OHI I I— C—C-C-HII iH H HHMeta allyl salicylio acid methyl ester was prepared acoord-ing to L. Claissen ^. The aeid was raade hy saponifying its ester.(Salicylic acid could not be used as a starting point since itsortho allyl ether rearranged to ortho allyl phenol with the lossof the carhoxyl group instead of forming the meta allyl salicylicacid). The acetyl derivatives of hoth the allyl acid and itsmethyl ester were not formed hy long and vigorous action of aceticanhydride. This confirms the predictions and forms a very inter-esting illustration of the phenomenon of sterio hindrance.The meta allyl salicylic acid and its methyl ester werehrominated in an ice bath. Such conditions are not favorable forbromine substitution in the benzene ring, and in fact, only amild evolution of hydrobromic acid was noticed in the case of theester and practically none with the acid. That the product ofbromination did not contain substituted bromine in the benzenering was proven by the fact that, upon treatment with alcoholicpotash, the residue gave no test for halogen. This is anothercase of steric hindrance, the carboxyl as v/ell as the ester group7.which cover the phenol radical ortho to the allyl group, prevented,to a large extent, the hrorainat ion in the "benzene ring and theformation of side products as descrihed in the case of the freephenol.Methylene coumarane of salicylic acid v/as prepared in tv/oways, oy reflnxing the dihrom allyl salicylic acid and its methylester, respectively, with alcoholic potash. This compound gave notest for halogen and no longer responded to the ferric chloridetest for the phenol radical.The analysis checked the theoretical. It is true that oneother possibility, namely, a compound having a six memhered ringcontaining an oxygen atom, would possess the same composition outtliat it is not formed is demonstrated by the mechanism of thereaction and proof of structure of methylene coumarane of benzene.Furthermore, upon bromination of the methylene coum.arane ofsalicylic acid, a monobrom product -was formed which did not reactv/ith alcoholic potash or alcoholic silver nitrate.oo-o/yocH8.Since our bromine atom added and hydrobroraic acid did not split.out v*ien the monobrom compound was treated with alcoholic potash,the evidence is conclusive that the bromine atom is attached tothe double bonded methylene carbon atom.EXIEHDIEIITALOrtho-Allyl Ether of SalicylicAcid Methyl Ester.Molar weights of methyl salicylate and allyl bromide, withan excess of anhydrous potassium carbonate and a anall quantityof acetone were refluxed on a steam bath for five or six hoursgave the ortho-allyl ether of salicylic acid.f f-/-/^r>-C-C=CI I I/V // //O H (iPurificationWater and ethyl ether were added to the flask containingthe reaction products. The potassium salts were separated bysiphonation of the aqueous layer. More water was added and 10^sodium hydroxide solution was gradually added from beneath theether layer with continual shaking, in order to prevent the form-ation of the tenacious emulsion, which readily forms upon theaddition of concentrated alkali solutions. (The length of timerequired for the emulsion, if formed, to hreak, causes a loss inthe yield due to saponification of the ester).When the concentration of the alkali has reached approxi-mately 8 - lOfo, a portion of the ether layer was tested withalcohol and ferric chloride for the presence of any phenolic com-pounds. If none were present, the HaOH liquors were siphoned offand were then replaced "by distilled water, and finally washed hysiphonation v/ith water till the alkali was removed, when testedwith litmus paper.The ether extract is separated from the water layer in aseparatory funnel and dried for a couple of hours over anhydrouscalcium chloride. The ether was driven off the ortho-allyl etheron the steam hath. The properties of the ortho-allyl ether ofthe methyl ester of salicylic acid have heen described. 3. P.130°, 10 m.m. Ref. Ind. 1.520, 20°C.Meta-Allyl Salicylic Methyl EsterThe ortho allyl ether was placed in a flask with an airreflux condenser, attached by a ground glass connection. A ther-mometer was allowed to dip into the ortho-allyl ether. Heat wasgradually applied. (Tapors of allyl bromide were driven off ifthe product had not been previously distilled). V/hen the temper-ature reaches 240°C., an exothermic reaction commences and thetem-perature rises to 2700o and remains constant from four to fiveminutes. The temperature then begins to fall and the liquid boils10.oonstantly at S6OOO. Hef. Ind. 1.538 - 20°C.—C-C-in//////The product boils within a range of two to three degrees, vaththe exception of a srriall residue which is not collected, it colorsferric chloride deep violet and a yield of of the theoretical,computed from the quantity of methyl ester of salicylic acid used,is obtained. (The rearrangement goes almost quantitatively.)Treatment of Meta-Allyl Salicylic Acid Methyl Ester withAcetic Anhydride.One mol, 191 grams, of K-allyl calicylic methyl ester wasreflused for several, hours with an excess of acetic anhydride.The excess acetic anhydride and acetic acid, if formed, were dis-tilled off under diminished pressure. 190 grams of product werecovered, B. P. 150°- 55 mm. Ref. Ind. 1.538 - 20^0. The exper-iment has been repeated with the same results. The acetyl deri-vation had not been formed.Meta-b,r Dibrom Allyl-Ortho Hydroxy-llethyl Carboxy Benzene.A molar weight of bromine was gradually added to a mol ofm-allyl salicylic acid methyl ester, dissolved in carbon disulf id,with constant shaking, i'he reaction was cooled by an ice bath.11.HydrobromiG acid was evolved in small quantities during the additionof the hromine. The carbon disulfid was evaporated off and uponcooling and vigorous stirring, the oily mass solidified and wassucked dry on a fminel. The product crystallized from alcohol.M.P.7E.0-72.5°0. white granular crystals.Analysis.Wt. Sample V/t. Ag.Br. $^Grams Grams Bromine0.1986 0.2121 45.5Theoretical(Product could possibly have been ring brominated, but upon treat-ment with alcoholic potash, gave no test for halogen.)Methylene Ooumarane of Salicylic Acid..9 rIII',M-dibrom allyl salicylic acid methyl ester was refluxed withan excess potassium hydroxide dissolved in absolute alcoholforthree or four hours. The reaction products were diluted withwater and the resulting acid was precipitated with hydroclorioacid. M^?. of impure product 144 - 60C.A small portion of the product was dissolved in etherand12.allowed to crystalize on a watch g-lass. T^mo compoimds oould bedistinguished hy their different crystal forms; one which was moresoluble in ether tlian the other. :'he product was suhiected tofractional crystalizat ion. Six crops were obtained from a mixtureof ether and petroleum ether. The crystals from the second andthird crops melted most sharply, 152-4°C. These two crops wererecrystalized from ether and petroleum ether. These white finecrystals melted at 151 - 2°C : and when again recrystallised fromether and petroleum ether melted sharply at 152^0 . The productreorystallized from alcohol and water and readily sublimed. (Theresidue or last crop from the fractional crystallization were yel-low crystals of mercaptan or garlic like odor).Analysis.Weight of sample grams" " CCp absorbed, grams" " HgO " "" " Oarbon "" " Hydrogen "Carbon foundfo Hydrogen "fo Oarbon theoret icalHydrogen "0.28780.71510.12720.19450.014267.84.9568.24.55Bromination of Methylene Ooumarane of Salicylic Acid.13.ITo 1.5 grams of methylene Goumarane of salicylio acid dis-solved in ether were gradually added 1.6 g. oromine. The temper-ature of the reaction was kept at ahout 0°C. hy an ice hath.Such small amounts were used that no hyajrohromic acid vapors werenoticed. The ether was partly evaporated off and crystals separ-ated out. The crude crystals melted with decomposition at E16°0.The product recrystalli zed from ether and petroleum ether.Y/hite needle like crystals melted with some decomposition, atE18-22000. Crystallizing again, compound melted without decomposi-tion at 222-3°C.Analysis.Wt. Sample grams Wt. AgBr grams ^ Bromine0.1630 0.1261 32.9Theoretical ^-^'^Propert ies.The orominated product of methylene coumarane of salicylicacid was treated with alcoholic potash, no KBr separated out; itwas also treated with alcoholic silver nitrate, and the reactionhy no means was complete for, if any, only traces of AgBrwereprecipitated. Since HBr is so difficult to split out, it is veryprohaole that com.pound II is the one formed, because of the dif-ficulty to form a tripple bonded carbon.Ortho allyl ether of Salicylic Acid.To be absolutely sure that the ortho allyl ether of salicylicacid methyl ester had rearranged to meta allyl salicylic methylester, both v/ere saponified and their melting points tal^-en.14./ \— o-o-c-c/\ I I// //// //II- O—C-C ~CI I IA/ H ^i mol .48 grams of ortho allyl salicylic acid methyl ester,Ref. Ind. 1.520, was refltjxed with 20 grsms of KOH and sr.fficient95^ alcohol to hold reaction mixture in solution. The product wasprecipitated from the reaction products hy the addition of hydro-chloric acid and recrystallized by cooling a hot solution of alco-hol and water v/hich was saturated in respect to the ether acid.The ortho allyl salicylic acid crystals are shiny flakes whichIImelt at 64°0. Schichilone, gives the melting point as llS^c.The melting point is given hy Cohen and Dudley, also L. G la is sen.Meta-Allyl Salicylic Acid.ii:o// ^I I— c—c-cX/ I I I^ // /V—o/y-c-c =eI II//////59 grams of m-allyl salicylic acid methyl ester, Hef. Ind1.355, dissolved in 300 cc. of absolute alcohol, were reflu^ed with25 grams of potassium .hydroxide. After a couple of hours, t15.saponification v/as ooraplete. The prodnot was precipitated by dilut-ing the alcohol solution ¥/ith water and hy adding hydrocloric acid.It was recrystallized from ether and petrole-um ether: melted atTreatment of Meta-Allyl Salicylic Acid with Acetic Anhydrid.102 grams of m-allyl salicylic acid were refluxed with 25grams acetic anhydrid for five hours. The excess acetic anhydridand acetic acid, if formed, were distilled off at a pressure of 25m.ra. The oily residue was washed with water four or five timeswhich, upon standing, solidified.The product was crystallized from water and melted at 93^0.Sublimed product melted at 94°0. Colored ferric chloride solutionviolet. The acetyl derivitative of m-allyl salicylic acid was notformed.24 grams of m-allyl salicylic acid were dissolved in carbondisulfid. 21.6 grams of bromine were gradually added, with shakingat the temperature of stx ice bath. The bromination was smooth andMeta b,r, Dibrom Allyl Salicylic Acid.16.hardly any hydro-br ornic acid given off. At first the prodnot crys-tallized out in the carhon disulfid to such an e^itent, so that itwas necessary to add some ether to hold the reaction mixture insolution. Ahout one-half of the carhon disulfid and ether wasevaporated off and product was precipitated and then sucked dry ona filter. Crude product 160-16100. crystallized fromether andcarbon disulfid M.P. I6E-64OG. and white needle like crystals,whichalso crystallize from alcohol and water were recrystallized fromether and carbon disulfid M.P» 162.5 - 153. 5°C.Analysis.Wt. of sample grams Wt. of AgBr grams io Bromine0.3438 0.3858 47.4Theoretical 4/ .^dMethylene Coumarane Salicylic Acid from meta b,r, Dibrom AllylSalicylic Acid.10 grams Dibrom allyl salicylic acid dissolved in absolutealcohol was reflrjced with potassium hydroxide for four hours. Theproduct was purified as described before H.r. 151 Eixed H.i.152°.The writer wishes to acknowledge his indehteanessto Dr. Roger Adams and Lir. R. E. Hindfusz for theinterest shownand the helpful suggestions made during the progressof thisinvestigation.18,BIBLIOGHAPHYI. I. Olaissen EisleilD, Aimllender Cheraie 401, 21-119II. Schiohilone Gazzetta OhimicaItaliana 12, 449III. Cohen and. Dudley.Journal of the Chemical Socieiy92, 1'5'45L. Claissen, Berichte der DeutxohenChemisohen aesellschaft . 1912, 45, 3165.IV. I. Claissen. IbidV. Chemisohes Oentral-hlatt 1914, IV, 1213.TI. Harries & BusseBerichte der Deutschen GhemiscnenGesellschaft 28, 501-219UNIVERSrTY OF ILLINOIS-UHBANA3 0112 079828387

The synthesis of coumarane derivatives from salicylic acid

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The synthesis of coumarane derivatives from salicylic acid

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