é; _ 2:: E: ,r'. 3‘ UpFLfifl can“! . .. h 3_ Muchzgaq :tam. University PLACE IN REfURN BOX to remove this checkout from your record. TO AVOID FINES return on or before date due. MAY BE RECALLED with earlier due date if requested. DATE DUE DATE DUE DATE DUE 6/01 c:/CIRCIDateDue.p65-p.15 Synthesis of Para-Hydroxy 1-1, Diphenylbutane by means of Aluminum Chloride and the Prepar- ation of Ortho-Hydroxy lél, Diphenylbutane and 1 - Phenylbutylphenylether. THESIS Submitted 'to the Faculty of Michigan State College in Partial Fulfillment of the Requirements for the Degree of Master of Science. Cflr- ~ , Mr] x“; BYXA” Harold W3) Strickl er June, 1937. ACKNOWLEDGEMENTS The writer is greatly indebted to Dr; R. C. Huston for the following investigation. Upon his suggestion the work was undertaken. I also wish to express my sincerest appreciation to him for the kindly advice and helpful suggest- ions given me during the progress of this work. TABLE OF CONTENTS Page I. Introduction 1 II. Historical Resume 3 1. Early investigations of Aluminum Chloride. 3. Early investigations of Phenol Condensations 5 in which Dehydration Occurs. 3. Condensations of Aromatic Alcohols in which ‘ A 7 water is eliminated. ‘ 4. Aluminum Chloride as a Dehydrating Agent. 8 III. Experimental . 1. Preparation of Prepylphenylcarbinol. 10 2. Condensation of Propylphenylcarbinol with Phenol 15 by Means of Aluminum Chloride. A A.Isolation of P-Hydroxy 1-1, Diphenylbutane. 19 3. Preparation of 0-Hydroxy l-l, Diphenylbutane. 33 A,Chlorination of Prepylphenylcarbinol 33 B.Identification of Phenylbutylene 35 C.Isolation of l-Phenylbutylphsnylether 36 D.Isolation of 0-Hydroxy 141, Diphenylbutane 36 4. Condensation employing Friedel 8: Crafts Method of 28 5. Synthesis. A.Identification of the P-Hydroxy 1-1,Diphenylbutane Esterifioation and Bromination of the Ortho and Para isomers. IV. Summary v. Bibliography 30 3O 34 36 INTRODUCTION Aluminum chloride as a means of effecting chemical change has had an extensive and remarkably varied application in organic chemistry. It has been the subject of a vast amount of research every since Friedel and Crafts first proposed using it in obtaining condensation products. It has been instrumental in adding to our knowledge whole classes of bodies of the most diverse kinds. ’ Syntheses accomplished by means of'aluminum chloride almost invariably give considerable quantities of resinous or gummy products. More than one group is generally introduced. The moncsubstitution products tagether with a mixture of higher substitution products being simultaneously formed. They, however, can.usually be separated by fractional distillation. The catalytic influence of aluminum chloride is not definitely understood, although many theories have been advanced attempting to explain it, i.e., intermediate aluminum organic compounds which different workers have isclated(1). 0n the other hand, the action of aluminum chloride is frequently much more complicated, inasmuch as we also find.decompositions, splitting off, internal condensations, transference of the alkyls as well as the formation of synthetic products. A tabulation of references to some of the complex reactions follows: (3)Anna1en 235 : 150 - 329 (3)Anna1en Chim. Phys. (S) 1.449 (4)Carbon Compounds — Porter, page 431 (5)0hemical Reactions - Falk, page 103 (6)0rganic Chemistry - Cohen, Vol. I, page 195 3. James F. Norris(7)thinks that aluminum chloride plays the role of a true catalyst in cases where no aluminum addition compounds exist. Quoting from his article, ”A mole~ cular attraction exists, which results from residual affinities. Two molecules when brought tOgether must exert an influence one on the other, and this must result in a change in the attract— ions betwesn the atoms within each molecule. Solvents have a marked effect on the rate at which a given reaction proceeds. From the foregoing point of view they act as true catalysts by altering the strength of affinities between atoms in the molecule. When changes set up in the affinities lead to increased react- ivity the added substance is a positive catalyst. If on the other hand, the reactivity is reduced, the substance functions as a negative catalyst“. Thus it is seen that there is considerable work yet to be done in which aluminum chloride is used as an agent in bringing about chemical changes in organic reactions. The present investigation was conducted to ascertain the products obtained by condensing propylphenylcarbinol and phenol by means of aluminum chloride (in which there occurs dehydration) and also to determine if Friedel and Crafts method could be employed in preparing the same compound, since it appears they encounteredz//T difficulty in such condensationge). It might further be stated that a comparative study of the quantities and products obtained by the above methods of synthesis may later lead to a clearer understanding of the re- actions involved. HISTORICAL RESUME 1. Early Investigations g; Aluminum Chlorid . Thirty-seven years prior to Friedel and Crafts observation that aluminum chloride could be used as an effective ‘ method of synthesis, Kuhlmam found that aluminum chloride could be used in preparing others. In 1840 Kuhlmann (9) (Untersuchungai uber die Aether— bildung) prepared a number of others by the action of anhydrous metal chlorides on mixtures of alcohols. Aluminum chloride is given as one of the metal chlorides used. It was early observed that aluminum dust served as a very effective catalyst in decomposing solutions of certain halogen aliphatic compounds. In 1876 u. u. Gladstone and Tribeuo) published two articles entitled, ”Decomposition of Solutions by Aluminum in the Presence of its Halogen Compounds'. In these articlesthsy recommended the use of a small amount of the chloride, bromide or iodide of aluminum in preference to zinc or zinc-OOpper couple in cbtaining decomposition products of alcohols. The following year Friedel and CraftsCLI) communicat— ed their experiences relative to the action of aluminum chloride can. hydrocarbon chlorides, notably on amyl chloride. They found that when a cold solution of amyl chloride and aluminum chloride were allowed to react, a vigorous reaction took place in which H01 was liberated." 'and the combustible gases form saturated condensation products which do not absorb bromine”. They found that the Irinciple hydrocarbon formed consisted of the general formula CnH.n + 3, which indicated the formation of a different hydrocarbon of the same group. When Friedel and Crafts employed this method in the presence of aromatic compounds they were able to synthesize homologues of benzene. The employment of aluminum chloride has come to be termed in organic chemistry,'Friedel and Crafts Reaction",and the salt, "Friedel and Crafts Reagent”. It appears that Friedel and Crafts encountered difficulty when they applied their procedure to alcohols and phenols. Quoting from Friedel and Crafts pub- lication(8) "We found in general that compounds containing the 1// group OH or OR, i.e., alcohols, phenols, acids and their ethers undergo decomposition with chloride of aluminum and the reactions which we have described are usually impossible in the presence of such bodies“. 3. Earlr.lnrssiisaiisna of Ehsacl.22ndsaaeiisns_ ‘ Ashleigh Qahrdrsiisa.ossura. A number of inportant cond ensations have been effected by the union between molecules with the elimination of water, but prior to 1914 the chief dehydrating agents con- sisted of concentrated sulfuric acid, acetic anhydride, zinc chloride, phosphorus pentaoxide, hydrochloric acid and occasion- ally by heating to high temperatures. In 1871 Aldolf Beeyer<13) (fiber die Phenolfarb- stoffe) condensed two molecules of phenol with one molecule of phthalic anhyiride in the presence of concentrated sulfuric acid. The following year Baeyer<13) showed that benzaldehyde and phenol could be condensed by using’concentrated sulfuric acid which eliminated water. Many other condensations are cited in this article. Thirty years later he(14) showed that triphenylcarbincl and phenol will react in the presence of glacial acetic acid and concentrated sulfuric acid to give para hydroxy tetraphenylmethane and water. Auer(15) found that phenol and absoluc alcohol L” gave ethyl phenol in the presence of zinc chloride. Mars and Weith(16) have shown that aluminum chloride acts upon phenol to give diphsnylether. Mazaara‘179 condensed isobutyl alcohol and phenol with magnesium chloride and obtained isobutylphenol (with the elimination of water). He also records obtaining a substance insoluble in potash and supposes it to be the corres- ponding isobutylic ether. (- Ipat'ev, Orlov and Petrov(13) have recently shown, that phenol and methyl alcohol will react to give ortho cresol. methylphenylether together with xanthene and other by products. They used ARCH). and heated the mixture under pressure. 3. angengatign 9;,Aromatic Alcohols in_Which ma law (/7 ' En 1873 V. Meyer and Wurster showed the first possibilities of condensing aromatic alcohols with aromatic ‘hydrocarbons. They used sulfuric acid as a dehydrating agpnt with which they condensed benzyl alcohol and benzene to diphenyl- methane, according to Baeyer's aldehyde synthesis.(13). They also report finding some by-products.oflligh boiling point. Hemilianmo) found benzhydrol (a secondary aromatic alcohol) could be condensed with benzene in the presence of phos- phorus pentaoxide to give triphenylmethane and water. He(31) ' also found that fluorenyl alcohol and benzene gave water and diphenylene-phenylmethane.lhen toluene was substituted for ben- zene diphenylene—tolylmethane and water were formed. Seven years later Ad. Liebman(33) (Synthese der Homologen Phenols) was successful in condensing isobutylalcchol,. amylalcohol and benzylalcogfifiAby using zinc chloride. Sen- kowski<33) and Ansohutz<34) later showed that the condensation 9/ products obtained by Liebman belonged to the para series. The following year Liebman(35) reinvestigated his previous work and found that small amounts of’ethers were obtained in the condensation reactions. He was also successful in condensing benzyl chloride and phenol with zinc chloride. Ree.tions in which Friedel and Crafts encountered difficulty with aluminum chloride(é). Fischer(26) found that by using zinc chloride, dehyr ation occurred when benzyl alcohol or diphenylcarbinol was f‘ndensed with dimethylaniline. 4. Aluminpm Chloride gg g Dehydrating Agent. In 1881 Merz and Weith(15) found that aluminum chloride exhibited dehydration prOperties similar to zinc chloride. They found that phenol and aluminum chloride would react at 300° to give benzene, diphenylether and methylene- diphenyl oxide. Graebe(37) in 1901 showedthat aluminum chloride was capable of effecting dehydration between a mixture of benzene and hydroxylamins with the formation of aniline. It appears that no further investigations were_ conducted in regard to the dehydration prOperties of aluminum chloride until in 1914 when Frankforter<38) and his cc-wcrkers published two articles in which they found condensation occurred with the elimination of water when chloral bromal, trioxymethy- lens and chloral hydrate were allowed toreact with certain organic compounds. In 1915(39) they published another article in which they extended their investigations to the polycyclic hydrocarbons. Huston and Friedeman(3°) were the first to investigate the dehydration prOperties of aluminum chloride upon mixtures of aromatic alcohols and aromatic compounds. In these investigations they have outlined a very important method for the preparation of synthetic compounds. In 1918(31) they extended their investigations . to experiments including the action of secondary alcohols on benzene, i.e., benzhydrol (a true secondary aromatic alcohol) methylphenylcarbinol and ethylphenylcarbinol (mixed aromatic aliphatic alcohols) in which they obtained triphenylmethane, diphenylethane and diphenylpropane respectively. They found a larger yield and smoother reaction was obtained with benzhydrol than with methylphenylcarbinol and ethylphenylcarbinol, the later having the greatest retarding effect. Hence they con- cluded the longer the parafin chain the more retarding effect it exhibits;. In 1924. Hustcn(32) found that benzyl alcohol and phenol would condense in the presence of aluminum chloride to give parabenzylphenol and that the phenolic hydroxyl group does not interfere with the substitution of the benzyl group in the benzene ring under the described conditions. The present work, as stated in the introduction, has consisted of an investigation of the condensation obtahnei when aluminum chloride is allowed to act upon a,mixture of propylphenylcarbinol and phenol. The condensation will also show the effect which the propyl group maiéfains in mixed sec- ondary aromatic alcohols of'the type R - - CHI when they are condensed with phenol. The methyl and ethyl compounds have been investigated by Huston and his co-workers(33). 10. III Experimsntal 1. Preparation p_f_ Propylphenylcarbinol. Propylphenylcarbinol can be conveniently prepared in excellent yield by means of the Grignard Reaction. The best results are obtained when heat is not applied and particularly by controlling the relative proportion of the reactants. Ethyl- phenylcarbinol has been recently investigated by Meisenheimer(34l He found that the best results ccmdd.be obtained when the Grignanl reagent and tie benzaldehyde were in the pr0portion 3 : 8, other- wise large quantities of benzyl alcohol and high boiling by- products are obtained. Rheinboldt and H Roleff(35) (Reducing Action of Organo-Magnesium Halides) showed that the reduction of Grignards reagent increases greatly with rise of temperature. H. Gilman and Roy McCracken(36) (The yield of some Grignard Reagents) have shown that the average yield of R.Mg 1 obtained from n-butyl bromide and magnesium is 91.23%. The following amount of benzaldehyde used (in order to maintain the proportion 3 : 3) was calculated upon the basis of obtaining a 90% yield of the R Hg x compound: P202111...” on flMQLWM 3 Moles N PrOpyl Bromide 368.9? gms. (in_1100 cc. of‘ 3 Holes Magnesium ribbon 78.96 .. ether) \ Ether 1000.0 cc. Benzaldehyde 265.08 gms. (in 500 cc. of ether) 11. The magnesium ribbon was thoroughly cleaned by using emery and filter paper. The ribbon (out about 1 cm. in length) was placed in:a dry clean five liter balloon flask. A small crystal of iodine was also added. The flask was closed with a three holed stopper carrying a mercury sealed stirrer, a drOpping funneland a reflux condenser to which was attached a calcium chloride tube containing calcium chloride and soda lime to exclude CO, and moisture*. Great care was observed in using anhydrous reagents. The ether used had just previously been distilled from sodium on to sodium. In order to start the reaction only 500 cc. of the ether was poured onto the magnesium through the reflux condenser. The mechanical stirrer was set in motion and the 368.9 g. of n—prOpyl bromide dissolved in 1100 cc. of ether, was slowly added through the dropping funnel. After about 100cc. of the propylbromide solution had been added a vigorous action occurred. The reacting mixture was cooled with running water to a slight visible reaction and the remainder of the other (500 cc.) was added to the magnesium ribbon. The népropyl bromide other solution was then added slowly through the drcpping ftmnel with—constant stirring at room temperature + See Gilman and Meyers in their study 9f optimum condition for preparation of R Mg X compounds 3 . 12. over a period of 8 3/4 hours’. After the propyl bromide solution had been added only traces of magnesium remained in the flask. The mixture was cooled with ice water and the benzaldehyde (previously dried over CaCl. and freshly distilled) dissolved in 500 cc. of ether was slowly added through the dropping funnel over a period of two hours. When most of the benzaldehyde had been added a whitish semi-crystaline mass appeared. After standing twentybone hours, it was poured onto finely crushed ice and shaken. An emulsion of a whitish oil appeared. The mixture stood for an additional 8 1/3 hours. It was then further decomposed by cold dilute H01 in order to facilitate extraction. The ether was distilled off and the remaining portion was subjected to fractional distillation. The third fractionation yielded: 88° - 92° at 8 mm pressure (most 90°-93°) 37.0 gms. 98° - 98° at 8 mm pressure (most 94°¥98°)393.8 ' above 98° at 6 mm pressure 1.0 ' The yield of the sac-sec portion gives 78.3% of the theoretical (based upon the amount of benzaldehyde used). The specific gravity of a portion boiling between 94°--98° at 8 mm. pressure was determined as 0.91: at 18°/40. A second preparation of the carbinol gave a very excellent yield. The same technique was employed as in the first preparation,with the exception that the benzaldehyde (freshly distilled) was not dried over CaCl. and that the I See H. Gilman and Meyers, J.Am.Chem.Soc. 45:159(1923. They find larger yields of R.lg X compounds are obtained by large quantities of anhydrous ether and slow addition at room temperature. Z .I/ ~ 13. mixture was allowed to stand twelve hours instead of eight and one half hours just prior to being decomposed with cold dilute H01. The following are the amounts that were used: Progortions gnd Agountg g; Reggentg yggd J 1 mole N-Propyl Bromide 204.4 gms (in 810 cc. of ether) ~ 1 ' Magnesium Ribbon 40.4 ' ‘ Ether 580.0 cc. Benzaldehyde 148.8 gms. (in 400 cc. of ethefl The above yielded upon fourth fractional distillation: 88°-92° at 8 mm. pressure 9.9 gms. 920-940 ' ' ' ' 8.8 ' 940-980 " " " " 188.9 ' The yield obtained in this preparation ' (sec-sec fraction) gives 81.2% of theoretical. It gave a specific gravity of 0:914 at 180/40. .A portion of the carbinol (940—960) was put into a freezing mixture. In a short time it solidified to a mass of white crystals, which melted at 14:80. This agrees with the melting point of'the carbinol prepared by Fritz Straus and Hans Grindel(38) who give M.P. 14.50 and B.P. at 19 mm. pressure 1140-1150. August K1ages<39) reports the boiling point of propylphenylcarbinol as 110° under 15rmm. pressure. He gives the specific gravity of the carbinol as 1.0212 at 180/14 and its chloride as 0.9124 at 180/49. It appears that the specific 14. gravities reported by Klages should be just the reverse. The phenylpropylcarbinol reported by Grignard(‘°) is blo 1130-115°; do a 0.997; d 4/13.? a 0.9881. This is in fair agreement with the density which I hare found, i.e., 0.974 at 180/40. I also had occasion to prepare the chloride of propylphenylcarbinol i// and found the specific gravity to be 1.0182 at 180/40. If one compares the boiling points reported by different investigators there seems to be some discrepancy. Etablissements Poulenc Fieres Fr 532, 484 Chem. Abs. 18:989 (1924) gives the boilhng point of the carbinol at 119° under 12 mm. pressure. M. Puyal and M. Montagus(41) report propyl- phenylcarbinol 1150-117o under 12 mm. pressure. The first preparation of propylphenylcarbinol appears to have been made in 1891 by T. R. Marshall and W. H. Perkin(‘3). They prepared the carbinol by the reduction of benzoyltrimsthylene. //,CH. H C.H.COCH.\\I + 3H.== C.H.C(OH)CH,.CH..CH. us They found that the carbinol distilled between 188°-170° under 100 mm. pressure and identified it by a combustion analysis. 15. 2. Com ensation 9; Propylphenxlcarbinol With Phenol p1 means 2; Aluminum Chloride, Four condensaticns were made: First andengatiggz- In the first condensation the following pro- portions and amounts of'reagents were used: ’f x~l Mole Phenylpropylcarbinol 60.0 gms..12 J1 ’“‘:c T 1 I Phenol 37.6 s “n‘if [VLNh ‘ .5 ” Aluminum chloride (anhy.) 26.7 “ Anhydrous Petrolic ether 1000.0 cc. The carbinol and phenol were dissolved in 1000 cc. of anhydrousxntrolic ether (dried over Caflla) and placed in a Jar which was fitted with a mercury sealed mechaiical stirr- ing apparatus. The jar was fitted with a four holed stopper, carrying a mercury sealed stirrer, reflux condenser, thermometer, and a tube for introducing aluminum chloride. The glass tube was tightly stcppered when not in use. A calcium chloride tube was 'used to exclude moisture. The mixture was stirred vigorously and the aluminum chloride was added in small portions over a period of one hour. Upon the first addition of aluminum chloride a milky color appeared which later turned to a.brick red color. Inside cf half an hour a pale reddish gummy substance began to deposit on the walls of the jar and thermometer. H01 gas was quite noticeable The temperature gradually rose from 20° to 28° then slowly de- clined. The mixture was stirred for one half hour longer, allowed to stand 1 3/4 hours and then stirred for 2 3/4 hours. After standing over night (10 hours) the reddish granular substance was 16, extracted with ether. The ether was distilled off and the remaining portion subjected to distillation under diminished pressure. The first distillation yielded the following? up to 102° (atmospheric pressure) discarded 85° - 125° at 6 mm. pressure 6.2 gms. 125° - 1750 ' ' ' “ 29.8 ' 175° - 250° " " " " 6.8 ' above 250° " " " " 18.5 ' Second Condensation;— The seccni ccni ensation was carried out pract- ically the same as the first, with the exception that only 400 cc. of petrolic ether was used. The time of addition of the aluminum chloride was 2 1/4 hours. The reaction appeared to proceed the same as in the first condensation. Care was not taken to use anhydrous ether or exclude moisture. The second condensation yielded the following on first distillation: up to 105° (atmospheric) discarded , 850 - 125° at 6 mm pressure 18.9 gms. Z/// 125° - 170° " " " ' 37.6 " 1700 - 220° ' " " " 28.1 " above 2200 ' ' ' ' 10.9 n f A portion of the ether extract was overl coked . . to the second condensation, and was added 17. Third Condensation:- Proportion§.§nQ_Amounts‘9;_Reagents Used. ”1 1 Hole Propylphenylcarbinol 60.0 gms. /35/».. ”\ 1.1 Moles Phenol 41.3 ' - ~/!' .56 Moles Aluminum Chloride 30.0 ' (Anhydrous) Petrolic ether 450 cc. The aluminum chloride was added over a period of 2 3/4 hours, keeping the temperature below 250. After standing for five days the residue was decomposed with ice water and extracted with ether. Its first distillation yielded: up to 1050 (atmospheric) discarded 85° - 125° at 6 mm. pressure 15.0 gms. 135° - 170° ' " ' ' 31.3 ' 170° - 330° ' ” ' ' 36.1 ” above 220° at 6 mm. pressure 17.5 ' The three above ccndensations were combined and distilled as follows. The three 85°“- 135° at 6 mm. fractions were combined and distilled at atmospheric pressure which yielded the following: ‘up to 1750 atmospheric 4.? gms. 175° to 190° atmospheric(motly phenol) 27.5 gms. above 1900 atmospheric 5.4 ' The remaining fractions were distilled under diminished pressure and after many fractional distillations (about 15) the following fractions were obtained:- 18. Final Qistillation g; the Three Condensations+ 91° - 143° at 6 mm pressure 2.4 gms. 1450 - 144 1/20 I I I 14.2 I 7 145° - 1500 I I I 6.2 I (1540 - 155° I I I 49.9 I V‘ 165° - 180° I I I 4.5 I 180° - 2100 I I I 7.4 I 2100 - 2130 I I I (most 2110) 12.0 I Q30 - 215° I I I 23.5 I 2160 — 2200 I I I 1.7 s 2200 - 2230 I I I 8.5 I 2250 - 2450 I I I 10.1 I . The 49.9 gms. boiling 154° - 156° at 5 mm. pressure, after standing overnight in the ice box solidified to a paraffin like consistency. It should be stated here that upon the third fractional distillation (prior to the above final distillation) there was fourteen grams boiling 1700 - 175° at 6 mm. pressure which also solidified to a paraffin like consistency Portions of this fourteen grams were dissolved in a number of different solvents to find a suitable medium; from which the compound could be purified by crystallization. One gram was recovered as a solid, the rest being used and a portion lost. + Note - The higher fractions from 180° to 2450 were only fractionally distilled about eight times. 19. An attempt was made to purify the above 49.9 gms. (1540-1560 at 6 mm.) in a similar manner. It was dissolved in petrolic ether and allowed to crystallize in the ice box. The compound crystallizes in long, very fine silky threads which soon takes on the appearance of a wad of absorbent cotton. Upon pressing out the petrolic ether between filter papers and allowing the remainder of the ether to evaporate in the ice box, a white compressed chalk-like mass is obtained. By following the above procedure, 5 grams of this chalk-like substance was obtained. The Br) 01> on, It is thusseen that the OH group passes the strongest influence to direct the entering group to the para or ortho position. However, in order to determine the charact- eristic difference between the ortho and para isomers, the ortho compound was prepared using Claisen's method of IRingalkylat- ion of Phenols'(49). He shows that ortho alkylation of phenols result when sodium phenolate is heated with certain alkyl halides in a non-dissociating medium. The employment of this method of comparison will furnish evidence as to which isomer is obtained in the aluminum chloride condensation.and also whether or not both isomers may be obtained. A 0 n f P o h c * Eighty grams of the carbinol (940-960 at 6 mm) were mixed with one and a half times its volume ofdry ether. Dry H01 was passed through for six hours at a temperature of 0°.- It was then.poured onto finely crushed ice, washed three times with cold water, extracted with ether and dried over anhydrous Na,SO.. The ether was distilled off and the remaining portion was fractionally distilled. After three f’References to ch orination of carbinols may be found in the bibliography 501 24. distilkiticns it yielded the following: 68° - 73° at 6 mm pressure 2.4 gms. 730—750 I I I I 79.0 a above 750 at 6 mm pressure 3.1 I The yield obtained was 89.3% of theoretical. It is a clear colorless liquid possessing a mild odor, resem- bling somewhat freshly graded orange peel. The specific gravity was determined and found to be 1.0182 at 180/40. L/I Amount; and Progggure Egg; ;p_01aisgn's andengation 10.7 gms. of Sodium 48.3 I I Phenol . I . "uf 78.5 I I cfl-Chloro pgsgylbenzene 125.0 I I Toluene The finely chipped sodium was suspended in the toluene and the phenol was added. After a few minutes a vigorous action took place Which gradually diminished in in- tensity. The mixture was heated on the water bath for two hours after which no sodium could be seen in.the flask; The mixture was cooled and the chlorinated carbinol was added. No reaction was apparent. It was heated on a water bath fer an hour (150° ~ 160° thermometer in oil) after which it stood over night. It was heated for 20 additional hours at 150 - 160o (with the exception that the temperature rose to 2000 a couple of times). The mixture was cooled, washed twice with water 35. (to free from sodiumchloride) and heated to 120° to distill off the water and toluene. The residue was dissolved in 250 cc. of Claisen's alcoholic potash solution (Ann. 442 : 224) and shaken out with 200 cc. of petrolic other using 50 cc. portions. .' The remainder was acidified with H01 (1 t 1) a and 125 cc. of water was added to dissolve the sodium chloride. It was cooled and extracted three times with diethyl ether. The above petrolic ether extract after four fractional distillations gave the following: 8.3 gms. boiling at 600—610 at 6 1/2 mm pressure 16.6 I I I 123o-1250 I 6 mm. pressure 11.8 I I above 2000 I I I -e B. Idenpificapign of Bhenylbgtylgng The 8.3 gms. portion boiling (60-610 at 6 1/2 mm.) was identified as normal phenylbutylene(51). Its boiling point was found to be 186° - 1880 (atmospheric). The specific gravity was found to be 0.9051 at l6°/4°. Its dibromide foamed in chloroform solution with the calculated amount of bromine gave long slender needles which melted 700-71°. I ‘ ' It seems reasonable to expect that some _ phenylbutylens might be obtained since Radziszewski(51) obtained. his phenylbutylene by the action of bromine on boiling phenyl- butane and then distilling at atmospheric/przfggxg: Genvresse(53) found that alpha-chloro propylbenzene could be converted into the unsaturated allylbenzene by‘boiling with KOH. 26. 0. Isolation of 1 - Phenylbutylphenylether The 16.6 gm. portion boiling 1230-1250 at 6 mm. pressure was a light mobile colorless liquid with a very faint geranium like odor. Its specific gravity was found to be leaflet 1%. I It was identified by two combustions which yielded the following: #1 Substance .2663 gms.; cc, .8278 9118.; 11.0 .1906 gne. #2 I .2480 I 00. .7708 I H20 .1765 I Calculated for 0133130 Found ( H = 8.009% #1 ( 0 =- 84.771% H = 8.020% c = 84.9061: # ( H = 7.983% 2 ( c = 84.765% According to Claisen(49) it is to be expected that some ether is formed t0gether with the ortho alkylation product. The formation of the ether probably occurs according to the following equation: C.H7 0 - 01 + NaOC) 9—9 0.H7 9- CC + N801 -H H D. Isolagion g; Ortho-Hydroxz 11, 1_Diphenylbu§ang The diethyl ether extract of the acidified alcoholic potash solution (page 20’) yielded upon four fractional distillations the following: 37. 10.4 gms. boiling at 75°—125° at 6 mm pressure(most1y phenol) 20.8 I I I l44°-l46° I I I 7.0 I I I 146°-200° I I I I 4. 7 I I above 200° I I I I The 20.8 gm. portion boiling at 1440-1460 ( 6 mm. pressure) was a light straw colored viscous oil, which would not crystallize when placed into a freezing mixture or allowed to stand in the ice box for many weeks. Two oombustions were made which gave the following results: . #1 Substance .2535 gms.; cc, .7865 gms.; 8.0 .1818 gms. #2 I .2521 I 00, .7829 I 2.0 .1817 I ' fr Calculated for 0168180 Found #1 (H:- 8.025% Ha 8.020% ( c = 84.615% 0 a 84.906% - #2 (Ha 8.065% ( c = 84.6955 28. 4. Ergparation g; Para Hydrogz 1-1, Diphenyl- butane Employing Friedel and Crafts Reaction. -0ne condensation was run in which Friedel and Crafts reaction was used, in order to determine if this method could be successfully employed in obtaining para hydroxy 1-1, diphenylbutane. Friedel and Crafts reported finding such react-5 ions as usually impossible(3). Also by comparing Huston and Friedeman's reaction with Friedel and Crafts reaction, it affords a method of determining the relative influence maintained by the hydroxyl and chloride groups in such reactions. Amounts 2;,Reagentg‘flggd \* lflfuole (irChloro propylbenzene 60.0gms. I I l/II Phenol 33 . 47 I .5 I Aluminum Chloride 23.7 I Petrolic ether (anhydrous) 500 cc. . The same apparatus was used in this condensation as was used in the preceding condensations. Anhydrous materials were used and the apparatus was fitted with a calcium chloride tube to exclude moisture. The aluminum chloride was added in small portions over a period of 2 3/4 hours. This rate of addition allowed the temperature to rise from 20° to 25° (no external cooling). After about 2/3 of the aluminum chloride had been added the temperature began slowly to fall. In this condensation when 2 to Jigrams of the aluminum chloride had been added a gummy mass appeared in the bottom of the jar. .It continually increased and toeard the end 0f the run became . R 29. semi-granular. When all of the aluminum chloride had been added it was stirred for 1 3/4 hours. It was allowed to stand 1 1/2 hours and then stirred for an additional 3 1/4 hours. After standing over night (14 1/2 hours) it was decomposed with ice water and dilute H01. It was then extracted with ether and dried over anhydrous K,00,. After heating to 100° it was fractionally distilled under diminished pressure. Firs; Distillat 19g 80° - 110° at 6 mm. pressure 8.7 grams 110° - 2000 I I I I (most 1800-200°)51.5 I 2000 - 2350 I I I I 14.1 I After six fractionations of th: last two fract- ions (above) the following was obtained: Ping; Distingt 19;; 80° — 1100 at 6 mm. pressure 8.7 gns. 145° - 1540 I I I I 4.0 I 1540 156° I I 21.1 I 165° 167° I I 6.6 I 170° 180° I I 6.7 I 1800 200° I I 2.8 I 200° 235° I I 19.7 I A Iggtificfiign p; E-Hydroxy 1:1, Diphenylbutgne The fraction boiling 154°-156° at 6 mm. pressure, when left in the ice box over night (without seeding) solidified in the manner characteristic of para hydroxy 1-1, diphenylbutane. It was further identified by the melting point of its benzoyl derivative (700-710). From this preliminary investigation it would appear that there is no great difference between the activity of the hydroxyl and chloride groups under the above conditions. Perhaps it should be pointed out that there was no fraction obtained between 110° to 1450 (6 mm. pressure) as was found in the preceding condensations. N0 high boiling fraction above 2350 at 6 mm. pressure was obtained. 5. Esggrifigation m 1119118631211 91 mg Orpho 2.32. Pagg isomgrg. The benzoyl derivatites were prepared by the Schotten-Baumann method of esterification. This serves as a means of identifying the phenolic hydroxyl group. One gram of the purified para hydroxy 1-1, diphenylbutane; obtained from the propylphenylcarbinol and phenol cond ensations, was dissolved in the calculated amount of KOH, using just sufficient water to cause solution. The calculated amount of benzoyl chloride was added. It was kept cool and after shaking well for 1/2 hour it became semi crystalline. After allowing to stand over night and washing with water to free from impurities,it was crystallized from alcohol. The long retangular crystals after purifying, melted at 70°-71°. 31. The oily residue (filtrate portion) which solidified to a jelly like sticky mass (page/7) gave a benzoyl Lz' derivative melting 700 - 71°. This fact indicates that most of the 49.9 gns. boiling 154° - 1560 (6 mm. pressure) is para hydroxy l-l, diphenylbutane. Crystallization is apparently hindered by slight impurities. The benzoyl derivative prepared from the con— densation product obtained by Friedel and Crafts method ( 21.1 ms. boiling 1540 - 156° at 6 mm. pressure) gave long rectang-/ ular crystals melting 700-710. Thus furnishing additional proof that the products obtained in the two methods of synthesis are identical. The benzoyl derivative of the ortho compound (obtained by Claisen's condensation) failed to crystallize from alcohol or dried petrolic other but remained as a sticky,gummy mass, inwhich very few crystals appeared. No further investigat- ion of this compound was made at this time. The fraction obtained from the three combined carbinol and phenol condensations 14.2 gms. boiling at 143-144 1/2° (at 6 mm. pressure) after purifying by Claisen's alcoholic potash, gays 11.5 gms. boiling 1430-1470 at 6 mm. pressure. Since this fraction corresponds closely to the boiling point of the ortho compound (Claisen's condensation) its benzoyl derivative was prepared. The product obtained consisted of a sticky, gummy mass, which from all appearances seemed to be identical with that obtained when the ortho compound was used. Thus there is an indication that there is a small amount of the 33 ortho compound formed in the carbinol and phenol condensation. In order to furnish additional evidence three brom derivatives were prepared. The following products were brominated: #1. Nine grams of the ortho hydroxy l-l, diphenylbutane obtained from Claisen's method of condensation. #2. Nine grams of'the product boiling 1430-1470 (at 6 mm. pressure) obtained in the three carbinol and phenol condensations. #3. Twelve grams of the para hydroxy 1-1, diphenylbutane obtained from the three carbinol and phenol condensations. The 12 gms. used, was the filtrate portion that solidified to a jelly like sticky mass when allowed to remain in the ice box. Each product was dissolved in chloroform. The amount of bromine added was calculated according to the probable reactions. Cu 0.57 g -C‘_‘> on + 4Br c.1372I -<:2~os + 2‘HBr O .. E) .7 .. 0,87 g-C} + 4Br carpi-QM +2551- Ebullition of HBr was quite noticeable. The brominated products were allowed to stand for several days after which the ether was distilled off. The products did not crystallize. The boiling points are as follows: #1 (above) Entire product boiled 184-185o t 6 mm. pressure. 33. #2. 7.5 gins. 184° - 185° at 6 mm. pressure. 1.5 ' 185° -— 186 1/20 I I I #3 2.5 gms. 1870 - 1880 at 6 mm. pressure 9.5 I 1930 - 189° I n w s 'M--‘—\\ From the above facts (esterification and bromination) it is very evident that both isomers are obtained in the aluminum chloride condensation. 34. SUMMARY 1. Propylphenylcarbinol can‘be prepared in excellent yield by the Grignard Reaction if heat is not applied and by controlling the relative amounts of reagents ‘used. 3 2. Propylphenylcarbinol will condense with phenol in the pr esence of aluminum chloride to give para-hydroxy 1-1, diphenylbutane t0gether with a small amount of the ortho isomer. 0 ‘ 0 0.37 g - on + Dos A101. 5 0.57 g - Q08 4 8.0 III 0 0s 0,117 $1 - on + {308 “Cl: 5 0,H7 g -0 + 8,0 3. The yield of the above para compound (18.9% of theory) substantiates the fact previously found, that the longer the paraffin chain, the greater its retarding effect in such condensations. 4. d-chlorobutylbenzene will react with sodium phenolate to give ortho hyiroxy 1-1, diphenylbutane and phenyl- butylphenylether. O - O 0 .5 0.27 c - 01 + NaOQ‘—9 0.87 c -0 + 0.87 g - 0C} a H There is also formed a.small amount of phenylbutylene under the described conditions. 35. 5. It was found that the phenolic hydroxyl group does not interfere with the preparation of para.hydroxy 1-1, diphenylbutane when Friedel and Crafts method is applied under the described conditions. 0.27 c - 01 + Cos E21, C.H7 0 - Q08 + H01 8 s 6. By comparing Huston and Friedeman's Reaction with Friedel and Crafts Reaction the relative influence of the carbinol hydroxyl and chloride groups are found to be approx- imately the same. 7. The isomers readily yield to bromination and the para compound gives a crystalline benzoyl derivative. 36 . BI BLIOGRAPHY 1. Literature :.g iving Complex Reactions involving the use of Aluminum Chloride. I (1) custayson - Ber. 11:2151(1878), 13:157(1880) I - Bull. Soc. Chim. 42:325(1884) Steele - J. Chem. Soc. 83-4 : 1470 (1903) Scheicken 4 Buttgenbach _ Jr Prakt. Chem. 105:355(1923) (2) Annalen - 235 : 150 — 229 (3) Annalen Chim. Phys. (6) I, 449 (4) Carbon Compounds - Porter, page 421 (5) Chemical Reactions - Falk, page 103 (6) Organic Chemistry - Cohen, V01. I, page 195 (7) J. F. Norris - Ind. Eng. Chem. 16 : 184 (1924) (8) Friedel 4 Crafts - J.Chem. Soc. 41:116(1882) 2. Early Investigations of Aluminum Chloride (9) Kuhlmann - Ann. 33 — 34 : 97, 204 (1840) (10) u. Gdadstonr & Tribe - Bull. Soc. Chim. 25:67, 549(1876) (11) Friedel 4 Crafts - Bull. Soc. Chim. 27:48(1877) 3. Early Investigations of Phenol Condensations (12) Baeyer - Ber. 4:658(1871) (13) Baeyer - Ber. 5:25(1872) (14) Baeyer - Ber. 35:3018(l902) (15) Auer - Ber. 17:669(1884) (16) Merz and Weith - Ber. 14:189(1881) (17) Mazzara - Gazz. 167-168(1882) (18) Ipatev, Orlov & Petrov - Ber. 60B:130(1927) (19) (20) (21) (22) (23) (34) (25) (26) (37) (28) (29) (30) (31) (32) (33) (34) (3 5) (36) (37) (38) (39) (4o) (41) (42) 37. 4. Condensations of Aromatic Alcohols Meyer & Wurster - Ber. 6:963(1873) Hemilian — Ber. 7:1203(1874) Hemilian - Ber. 11:202(1878) Ad Liebman - Ber. 14:1842(1881) Senkowski - Ber. 24:2974(1891) Anschutz - Ber. 28t407<1895) Ad Liebman — Ber. 15:150(1882) Fischer - Ann. 206-85(1880) 5. Aluminum chloride as a dehydrating Agent Ber. 34:1778(1901) Frankforter - J.Am. Chem. Soc. 36:1511, 1529(1914) Graebe _ Frankforter - J.Am.0hem. Soc. 37-385(1915) Huston & Friedeman - J.Am. Chem.Soc. 38:2527(1916) Huston & Friedeman - J. Am. Chem. Soc. 40-785(1918) Huston - J. Am. Chem. Soc. 46:2775(1924) Huston, Lewis & Grotemut — J.Am.Chem.Soc.49:1365(1927) 6. References Cited in Experimental Part Meisenheimer - Ann. 442:180(1925) Rheinboldt & H. Roleff - J.Pr.Chem.109:175(l925) H. Gilman & Roy McCracken - J.Am.0hem.Soc.45:2426(1923) Gilman & Meyers - J. Am. Chem. Soc. 45:159(1923) Fritz Straus é Han Grindel - Ann. 439:276,312(1924) August Klages - Ber. 37:2312(1904) v. Grignard - Chem. Centr (1901) ii, 622-625 M. Puyal & M. Montague - Bull. Soc. Chim.87:857(1920) Marshall 4 Perkin - J. Chem. Soc. 59:885(1891) 38. References Cited in Experimental Part (continued) (43) Koenigs and Carl - Ber. 24:3889(1891) (44) Rennie .,J. Chem. Soc. 41:37(1882) (45) Paterno - Gazz 2, I (46) Rennie - J. Chem. Soc. 41:227(1882) (47) Fischer — Ann. 206:85(1880) (48) Holleman - Chem. Rev. 1, 186 (1924) (49) Claisen - Ann. 442:210(l925) (50) Alex Crechoff - Ber. 45:861 McKenzie - J. Chem. Soc. 1031. 687, 713(1913) Levene & Mikeska.- J. Biol. Chem. 7o:355(1926) (51) Radziszewski - Ber. 9:260(1876) (52) P. Genvresse - Bull. Soc. Chim. I, 219(1893) GENERAL REFERENCES Organometallic Compounds of Zinc ami magnesium (MonOgraph) - Henry Wren Organomagnesium Compounds in Synthetic Chemistry - reprint and circular, series of the National research Council Richter's Lexicon Practical Methods of Organic Chemistry - Gatterman Determination.of Radicals in Carbon Compounds - Meyer and Tingle Qualitative Organic Analysis - Ksmm Laboratory Manual ofOrganic Chemistry — Fisher Organic Chemistry ( 3 vols.) Cohen Catalysis in Organic Chemistry - Sabatier r—- Reid Organic Chemistry — Moureu. Manual of Organic Chemical Analysis - J.F. Thorpe & M.A. Whiteley 39. as II24 ,3? 1 34990 ||l||11111III!IIIHHHIUIIIWIIHIIlll‘lltllilfllel'Hl 31293 02244 8082