lHIHllWllWIHIHMI ‘. ~ E..‘-".:i;r!E {SEEMS DERWATIVE? ”LEMIYLPHENOLS 1:03 THE BEGRF‘; --—.¢l ». P": .? . .‘ . 5.4.2.11; a; peeland Fe, U;;..sm:;; 193’. LIBRARY ' f I , Stz;,-...‘:' Mmhigarl . _ ‘Univc-YSIW . g L _‘ . ‘ / i I _. *— 3033 BROfiO DERIVATIVES OF THE L”EZYLP¥EHOLS 80MB BROEO DERIVATIVES OF BE32YLPEENOLS 13" BRUCE LEELAND FEYBRWEATHER THESIS SGBHITTBD TO THE FACULTY OF MICHIGAN STATE COLLEGE OF AGRICULTURE AND APPLIED SCIEHGE AS PARTIAL FTLFILLKRYT OF THE RBQUIRDEBNT! OF TEE D?GREE 0F MASTER OF SCIEHCE. DBCEHBER 1931 AGKNOWLEDGLKENT Th6 writer IIIhOI to cxpros: hi. approaiatio: for tho kindly ‘Iniutano. and advice of Dr. R. c. Hun‘on without than. inspirstion uni guidance thin work would not htV. boon polaiblo. 331630 CONTENTS [interionl Pa;- 1. Early work on nlkylntioa of phenols 1 8. The work of 01:13.: I I. Tho work at Iriodul nnd Ornfts nnd tho 11013 condoncntion 1 The Problem Dotinod 13 Exporilontll 1. Prolininnry nut! 17 8. Propnrntion a! 3' iron 2 hydroxy di- phonyl nothano by Clainon'l nothod 10 8. AICI, condensation 31 4. Ptooi or identity of tho 8 iron bonxyl phenyl othcr 38 5. Proof of identity of the 2‘ bran z hydroxy di phenyl nothnno 4o 6. Check on identity of the 2' bran & hydroxy d1 phonyl nothanc 45 7. Fraparation of tater- 4| Sch... of Condensation GO HISTORICAL DATA 1. Early work on olkyletion of phenols. Since 5. Peterno. in 1078 (Gaza. Chin. ital. l. lee. (1878) prepared hie first benzyl phenol by hosting henzyl chloride with zinc dust and phenel, a great number of other experinenters have con- tributed to the science of chemistry e comprehen- sive and more or less conplete collection of labora- tory procedures and theories concerning the proper- ation of both the hensyl phenols and their related products. The object of this historical review it not to give e complete resume of their work but merely to trace the more important developmente along this line of organic condensetions which have. innocent- ly enough. brought forth the experimentation covered by this theeie. Paterno'e first work resulted in his isolation of hcnsyl phenol in the form of white silky needles (n.p. 84’.) He prepared various substitution pro- ducts with HHO and a sulionic acid with 3230‘s 8 In 1814. in conjunction with m. Fileti (Gena. Chin. itel. 8. 121--189, 251-~264) he prepared further derivatives with ecetyl chloride. benzoyl chloride. and bromine. Their di-bren derivative 1. 2. scene to have been held in acne doubt by later experinenters. (Zincke and Walter. Ann. 334, 801--3BI. (190%)) Again ii love. Paterno and lileti (Gaza. Chin. ital. I. :81) prepared bensyl phenol. This tine the condensation was effected by using henzyl alcohel and phenol. clan: with a mixture of 3380‘ and acetic acid to remove a molecule of water. Along with their known compound was obtained an oil which did not crystallize but was assumed to be an isomeric bensyl phenol.’ It remained for Rennie in 1882 (J. Chem. Soc.4l, 220. 1882) to prove the hensyl phenol which melted at 84' the para compound. We also one to him the identification of the oil. in Patcrno and Pileti'e exPeriment, as the ertho compound. Perkins and Hodglinscn (J. 0.5. 724, 1880) pre- pared a bensyl phenol. probably the para. iron the K03 solution of a nixture of phenyl acetate and benzyl chloride. This compound had a melting point of BO-ail‘. rurthsr condensations or this same nature were node by Leibnana (Ber. 15, 15:. 138:) using sine 3. chloride. Paterno and Haasaro (cats. Chin. ital. 8. 803-—30§. 1879) using sine turninge. and Hazarrc (Baas. Chin. ital. 12. eoo~~511. lees) using nag- neeiun‘chlorido. Bakunin (sass. Chin. ital. 33, 495--6. 190:) in the presence of zinc prepared bensyl derivatives of alpha and beta naphthol. Braun (Ber. 43. loco-~52. 1910) prepared others by boiling aromatic halogencids in the presence of H250. and alcohol. _ Johnson and Hodges prepared substituted phenols and others (I. Am. Chem. Soc. 35. 1014. 1913) by reducing the corresponding mixed hatches containing the hydroxyl or alkyloxy radicals in the benzene nucleus with zinc amalgam and hydrochloric acid. 1!. The work of Claisen. To Claieon goes credit for the development of the most satisfactory method of condensation of the alkyl halides yet devised. A resume of his work along this line is as follows (L. angew. chem. 36. d78-e9. 1923): An alkali phenolate was treated with an alkyl halide in a non dissociating medium. such . as toluene. VAfter heating. a product. principally ring substituted phenol with sons alkyl phenyl other. was obtained. The other was renored by washing with petroleum other after the mixture had been treated with alcoholic potash solution. The alcoholic potash tied up the phenols present in the tern of the potas- siun salts which were insoluble in petroleun other .and were later broken down by acidifying with 301. The production of a quantity of the ortho phenol came as a surprise since only the other was expected. Explanation of this reaction is nade by Olaisen after the manner of lichaol (J. pr. 31. 486; 40. 189) in connection with silver cyanide and methyl iodide. This is illustrated as follewos Q/‘OM’b O’NL J / \ C2 Cf' r- FZCZE-*4> (1 Cg'l4 ~—4> / \\ u l\ C” CH Q . l C40 COH ' , A ‘h l I Claieen claims unsaturated groups substitute in the ring nore readily than do saturated and that once alkylated the ring is more easily substituted .5._ .... r-~........ in than previously. Purthernors he states that in dissociating media such as alcohol the entire yield takes the ethereal fern while in non-dissociating media such as toluene and benzene yield a prepon- derance of the phenolic compound. claieon does not note the formation of any but the ortho compound in his reaction. Later investi- gators report traces of the para as well. The fact that benzyl chloride in toluene ferns others with phenols while diphenyl ohlcr methane gives only the carbon alkylated derivatives is held up by n. Busch (L. angsw. chem. 38. 1145-6. 1925) to be indicative that the tendency of bonsyl radicals toward carbon alkylation in phenols in- creases with the increasing substitution of the methane carbon atom. ' Busch and Knoll (Br. so a. 2243--57. 1921) working from phenol instead of the bonzyl group state that electro negative groups substituted in the ring of phenols favor the other formation. They also corroborate Glaisen's statement that the presence of alkyl groups in the phenol ring reduces other and favors phenol formation in future conden- satiens. 6. to are indebted to Claisen for many other contributions. In 1901 (Ann. 418. se--lzo. 1901) he rearranged allyl phenyl other to o-allyl phenol. Shorigen (Ber. 58 B. 2028. 1926) also worked on ad halogens rearrangements. Of particular interest to us is the work of Van Alphen (Rec. Trev. Chin. so. vet--312) and Short (1. Chem. 3... 131. use. 1928). The former heated bcnxyl phenyl other with zinc chloride to form the para phenol. the latter prepared both ortho and para benzyl phenol. phenol. and the di benzyl compounds from the same reaction. In 1925 Glaisen (Ann. 442. sic--46. 1926) describes several condensations along the same lines as those of his earlier work. Host important of these is his work on allyl bromide and para cresel. These most recent works of Claisen are an out- grcwth and application of a previous system of con- densation employing sodium worked out by him in 1871 (Ber. 20. see--650. 1871). K. van Auwers (Chem. Zontr. I. 2347--8. 192s) suggests three methods whereby carbon alkylation may take place. l. The method as outlined by Claissn. 2. The formation of the other and later rearrangement. 3. The separation of the metal as a metallic halide with the formation of the free alkyl and enol radicals. The enol rearranges to the kete and the radicals units. The reaction is as fallout. —0~ ’0/ '< 01" a l \/I ,. N > { v’ \ The first hypothesis is that most generally accepted for this reaction. Its possibility seens much more logical than the existence s! free alkyl and enol radicals. or the rearrangement of other in one media and not in another. III. The work of Friedel and Crafts and the 11013 condensation. While Friedel and Craft are generally given credit for being the first to utilize A1013 as a catalytic agent in the condensing of the alkyl halides. alcohols. and aromatic hydrocarbons. the first use of this condensing agent was Huhlnen (Ann. 33-¢84. 97-~804. 1840) who prepared ethers tron nixtures of alcohols thru its use. Not until 1877 did Friedel and Craft publish their observations on this type of condensation. (Bull. Soc. Chin. 27. 48. 1877: Compt. rend. 84. lees-~s. 1871). Their work at this time was en- tirely with aliphatic compounds and they go so far as to state that aromatic compounds and especially those containing the OH or 0" group can not be satisfactorily condensed by this method. They were very successful in their work with the ali- phatics but it remained for later investigation to perfect method: by :hi h the phenols. aromatic alcohols. and beneyl halides night he etfecisntly O In 1881. flers and fieith .Ber. 17. 18?) re- ported having prepared di phenyl other from the action of A1313 on phenol and indicated that 31613 here was acting as a dehydrating agent. Frieda! and Craft (Ann. Chin. Phys. 1. 489. 1654) advanced the following theory or the reaction of A1013 on an alkyl halide and benzene. 60/1’5/7’ + fl/c/j r—7/7/d +///\.CL5 /77/<:§ .» Hue --~> //'/p/.._ (Long \(H J J D) The addition product of o-chlorephencl and aluninnn chloride was isolated in 1896 by Perrier (Compt. rend. 123. l95--198. 189C). The product Inn Alzcl‘ (oc‘nzol), and use a white crystalline ' 9 powder melting at 201--ZIGP Huston and Friedenan (I. A. C. 3.. 38. 2827) in 1916 condensed benzene and benzyl alcohol te obtain di-phenyl methane. some p-dibensyl bensens. a trace of the corresponding ortho isomer. and snthracene as a by-product. In this reaction the £101, acted in the capacity of a dehydrating agent. It was found that the proportion of materials used as well as the temperature affected the fields of different products. These same men published in 1918 (J. 4.0.8.. 40. 785--93) work on the condensation of benzene with secondary alcohols. They used phenyl methyl carbinol. phenyl ethyl carbine! and di phenyl carbine] for this work. They found that as the 10. length or the paraffin chain gres. so its retard- ing effect upon the reaction inereased while the presence or the phenyl group did.not hinder the progress of the reaction. lustcn (I. s.c.s. at. sf1e--e. 1924) studied the action of £101, in the condensing of phenol and hensyl alcohol to give p-hensyl phenol. Bensyl chloride and phenol in the presence of £1013 gave so: of pohenayl phenol. The reaction mixture was carefully regulated as to tanperatnre. It eas round that eptinnn tenperatnre varied with the different conpounds being condensed. Huston and Sager (I. 5.0.Soe. 48. 195]. 11:.) applied the dehydrating street or alaninun chloride to saturated and unsaturated aliphatic and are- natie alcohols with benzene. to term the following conclusions. fl) That saturated aliphatic alcohols up to and including anyl alcohol do not react. (8) That unsaturated aliphatic alcohols. as allyl. do react. (3) That of the alcoholic derivatives of the aromatic hydrocarbons. only those having the hydrox- \ :1 group on the carbon aton adjacent to the ring react. In 1’27 hasten. Lewis and Grotenut (J. d.C. doc. 49. 1865. 19:?) extended the series ef eena densatiens of secondary aleohols with benaene to include that of secondary alcohols with phenol. in the presence of 1101;. They also observed that substitution is abetted by unsaturatien in the substituting nolecule. In 1929. Huston and lanfield (master's thesis) deternined the proportions of phenol. hensyl chlo- ride and a101, from which naninun yield ran to be obtained in 11013 condensation. This was found to be I nolar quantities phenol. l nolar quantities hentyl chloride. and {-nolar quantities 11c1,. Eldridge (Iaeter‘e thesis 1930) reports that the presence of tee chlorine stone on the phenol causes the formation of the ether in the Alcl' eon- densatien.. Es isolates and identifies the ether tron such a run for the first tine. he suggests that perhaps the ether is iorned first in all 1101, condensations and that rearrange-ant tellers. he believed that the presence of the halogen on the phenol rin; upset the valence equilibriu- of the ring causing a greater residual valence to be centralised in the oxygen nethyl ( )V/l unien of the ether thus tending toward a more stable cenpound. The nature or the way in which 1101, brings about the nany cendensaticns of which it is able renains sonewhat of a nystery. Three possibilities are allewed by the theorists on the subject. (1) catalytic actien. (3) lnternediate eenpeunde. (3) Dehydratien. The internediate eenpeunds at 51013 have been isolated. In some condensations results press it to he merely a catalyst er a dehydrating agent. IV. 'ork with breninated phenols. and bensyl hale- geneids and alcehels. The first work en the hrsninaticn oi bensyl phenol took place in 1814 when Paterno and rileti (case. Ohin. ital. s. 1:1--1ss; se1--ses. 137s) prepared a di bren derivative e: the p-phenol by treating with an excess or brenine in 68: soluti- Thoy obtained an anerpheus naterial n.p. 17!: This eonpeund has been questioned by Zinoke and Ialter. of when lore later. V Bintenie (Ann 101. sss) reports the prepara- ties of bonsyl brene phenyl ether by passing brenine into an alcoholic solution of the ether to which sons 330 has been added as a catalyst. Rennie (J. chon. Sec. 49. £08) in ices. pre- pared 8. 4. di bran d bensyl phenol altho he did not know it. A white eonpound unidentified by hin has been proven by laxfield (1'28 of this labora- tory) to be the above nentiened sonpeund. n.p. Cl, duwers (Ann 85?. coo-es. 1907) prepared tri- bron phenyl bensyl other and two di-bron derivatives. In these esperinents the tri or di bron phenol-was dissolved in alcohol and treated with the bensyl eonpound and sediun ethoxido. The nest notable contribution to this field was nade in 1’00 by Zinche and Walters (inn 38d. 861--38I. 1909). They prepared and identified di and tri brene derivatives e! p bensyl phenol. The nothed followed was that or adding the cal- eulated anount or bronine to a cold chlorofor- solution of the phenol and stirring until all brenins was in solution. They isolated an on- stable ccnpound of colorless noodles n.p. d: which changed to the stable torn of rhonbic crystals n.p. at! They gave this the iornula: Cjfigw< {LO-'5 M. H ---- --—*—/p,,' The results here do not check with the work of Paterno. The tri bron ccnpound was given the following formula: Wu “K.“ LQEK 3;” In 1920 Powell and Adana (1.1m. Ghen.8oc. d3. see-~3e. 1980) prepared p bren phenyl bensyl other by refluxing benxyl chloride. para bron phenol and potassiun carbonate in acetone solution. Van Alphen (Rec. Trav. Chen. 46. 790--818. 1921) breninated d. hydroxy tri phenyl nothane and obtained the di bron derivative. __.._,-+- _.._ *2 (“H5\g< . 50H / . l_ (VH5 o 14. 15. Iaxfield (fiaster's thesis 198’) reports that broninatien of phenol takes place in the phenol ring rather than in the bonzyl radical. He identified the two force of t-od di bren d bonzyl phenol found by Zincke and Ialters. Darcy. (master's thesis 1930) failed to isolate the ortho substitution product when p- bren benxyl chloride was condensed with phenol in presence of 5161.. He also checked and identi- fied the structure of d hydroxy. 8--d--d' tri bron di phenyl nethane as prepared by Zincts and falters (Ann 834. 367--388. 19040 His resulting conpound did not agree in physical characteris- tics with that obtained by these non. The Problen Defined. Analysis and identification are to be nads et all neneobenzyl conpounds resulting iron the 1101’ and Glaisen eondonsatiens of ortho bron benxyl chloride and phenol. is one step in the identification of the nono- benxyl phenols. a study is to be node .1 the posi- tions taken by the substituting groups in the tri bren none-hydrexyl d1 phenyl nethanos which will ‘0 prPII'Cde EXPERIEIERTAL DATA 17. l. Prelininary Verb Chlorination of c-Bron Toluene O‘l‘hrOI,-clz-o-G‘I‘Br033cl-HOl The nethod here followed is a nodification of that reported by Jacobs and Beidelberger (I. liel. on... so. see--es (1915).) They state that they passed chlorine (no anount stated) thru boil- ing e-bron toluene and distilled. This nethod was attempted with indifferent success. _It was found that while a small yield was obtained the chlorination had a tendency to go too far and introduce a second and a third chlorine atom into the nethyl group thus spoiling the reclaimed coupound for future use. By a slight modification of this method we were able to reclain all of the original conpound which was not halogenated. fer a future run. A weighed anount of e-bron toluene was placed in a weighed flash fitted with a reflux condenser and a chlorinating tube. s few crystals of rOl‘ were added as a catalyst. This flash was heated x to 1so'—-1oo' c. and chlorine bubbled slowly thru the brene toluene. The flash and contents were 18. weighed fron tine to tine until the increase in weight was just short of the calculated increase due to the roplaconent of the hydrogen in the nethyl group by the chlorine. The resulting nix- ture was distilled under reduced pressure. The e-bren toluene boiling 110'--11s° at is nn. 1. . clear colorless conpound which. however. becones cloudy on standing in sunlight. Caro nust be taken to keep even vapors of it fron coning in contact with the eyes. A typical run. Weight of flash a toluene 349.7gns. weight of onpty flash 159,1gns. Weight of toluene 100. gns. Calculated increase 30. gas. Flask weight at end of chlorination Iii. gns. Ancunt of e-bron benxyl chloride b.p. iio'--iis'--1s mm. 93.5gns. Yield 71.001 theoretical 19¢ 11. Preparation of I'bron 2 hydroxy di phenyl nethane by Olaisen's nethed. ,fiZZJ -0“ ’cflafip \"g (h. .— H {\y A,“ V “CD I p a; + e m 2 k Equinelar quantities of o-bron bensyl chlo- ride. sodiun. and phenol were used in this prepar- ation. 'Tho sodiun was cleaned of all corrosive and oxidised nattor and headed in dry toluene ever an oil bath. This was done by placing the sodiun and toluene in a three neck flash fitted with re- flux condonsor and stirring the nixture very rapid- ly Just as the toluene began to boil. The sodiu- innediately broke up into tiny globules which hard- ened as the flask was allowed to cool and stirring continued. The phenol was added over a period of two hours with constant stirring. It was found that the phenol and sodiun woald react nore cen- plotoly with one another if the phenol was added in the form of a toluene solution. In either case a white cheesy nass of sodium phenolate was forced. This was heated to'llo' for one hour with stirring and allowed to stand over night. The freshly distilled o-bren benxyl chloride 20. was then added all at once thru the condenser and the reaction nixture was heated to 100°--l00' with stirring on the oil bath for eight hours and again allowed to stand over night. i The Reel formed. was removed by washing with water. which in turn was removed thru a eoparatory ’ funnel. All renaining water and toluene was driven off by heating to 130. in a distilling flask. If all the toluene is not driven off. a cen- plete separation between the other and phenolic products can not be effected in the following step. The toluene free mixture was treated with an excess of Claiesn's alcoholic potash solution (the anount varied with the sins of the run frongloo to 500 cc.) which tied up all free hydroxyl groups present and rendered them insoluble in the petro- leun other which was new used to rencve the others present. Three washings with petroleum other were node and this extract reserved for further treatnent. The heavy oil remaining was acidified with a nixture of concentrated 301 and ice and extracted with ethyl ether. The other was driven off as far as possible on a water bath after which the extract 21. was transferred to a Claisen's flash and heated to 180’ to remove what other and water night still be present. The residual material was distilled under vacuul. It was found that results obtdned at 8 nm. using a netor were nuch better than those obtained at lbmn. with a water pump. The distillatss in the once were found to be nuch purer and to chew less signs of deconposition than in the latter. Several runs using small anounts were nads with conparatively unsatisfactory results. Dif- ferent nolar quantities of phenol and tins of heating were experimented with but the above pro- cess was found to be the nest satisfactory. Per cent yield was not calculated for these first four runs. Results of the first four Olaisen's and anounts of compounds used are below: 30 gns. e-bren bensyl chloride 3.6 ' eediun ld.d ' phenol 7! co. toluene I heated for seven hours 1 Products from distilling ethyl ether extract up to 180' 1.8 gns. leo’-zio' e.o - zlo°~ up 4.1 - residue 4. ' Second condensation 80 gns. 18 ' 4.0 ' 75 00s e-hren bensyl chloride phenol sodiu- toluene heated for six hours. Products from distilling ethyl ether extract 180. up to leo'-2lo' 210.- up residue Third condensation. so gns. 8.3 ' 18.3 ' ,3 Ode 4.4 gns. 5.0 ' 8. ' 6o ' e-bron benxyl chloride sodinn phenol toluene heated for eight heart. 32. Products fren distilling ethyl ether extract up to ieo' ieo'-zie' 810.- up residue Fourth condensation so gns. 3.8 ' 13.0 ' 76 so. heated for 8.0 gns. 3.8 ' fie. ' 3e ' eohron hensyl chloride sodiun phenol toluene eight hours. Products from distilling ethyl ether extract up to 180. ieo'-zio° 21o'- up residue 6.2 gns. 7. ' 4e‘ ' 3. ' It was found that in nest cases the fraction fron lBO‘coSlO. either solidified or became very viscous in nature. This was assumed to he the fraction desired. The four fractions were united and redistilled giving about is grane of a celer- lees conpound boiling between iss'--soo' which solidified in the ice box but returned to liquid form at reon tenperature. An attonpt was nade to purify hy crystallisation hut crystals obtained from ligroin in the cold passed back into the liquid state at roon tenperature. The conpound was returned to the hen and allowed to stand. The various fractions up to 180’ were found to be mostly phenol. while those above 210' were assumed to be the di bonsyl oonpound. The resib due was a high boiling tarlike compound which solidified on standing. into a brittle cakeliko slag. From the results of the above runs. it was decided that eight hozrs was the optimum tine of heating and that equi molecular quantities were to be preferred to excesses of any of the reacting substances. The petroleun other extracts from these four condensations were combined, the other driven off on a water bath and the remaining heavy anber oil distilled at 18 nm. The following fractions re- eulted. 24. 25., vs'- 125' ie gns. 125.- 110. 1,. s 110'- 195’ 20.2 o 195'. up 3.: - The fraction from 76°- 12!. was found to be o-brom benxyl chloridq,that from 128' to 110. was a mixture of the benxyl chloride and the other. The fraction from 170. - 195. was redistillod. the fraction from 175. - 179: some 12 gms.. coning over as a light yellow oil and solidifying in the re- ceiver. his solid was pressed between filter papers and then washed with cold alcohol. The solid diminished by half in mass but became color- less and crystalline in nature. when recrystalc _ lisod from hot alcohol. the white fluffy crystals were obtained which melted at 34° to 30: This was assumed to be the ether and analysis by the Parr sulphur bomb method gave the following result. Eght. of sample fight. of bromine 1 Br. Theoretical .3363 .07“8 31.08 ‘33:; .2104 .oeasc ’sggssll. so.s ?0,/’_7 This is conpound Number One (I) " “"" benxyl phenyl other. Two more claises's were run in order to ob- tain sufficient of the orthe compound to prepare derivatives and esters. In these runs half nolar quantities were used with the following results. Fifth condensation Ethyl ether extract at 16 mm. eo' - 1s:' 10 g... 185. - 180' .1 ' ieo‘ - ios' s.s - ioe’ - sos' 1e.o ' I 208. r up 10. ' residue 1!. ' Petroleum ether extract at is an. 00. . 125. if gns. ise' - ice. I - ivo’ - ion. so - 10'. - up 4 ' Again we found in the phenolic fractionation phenol coming over fron 96:123.. a nixture fren lZO.--180.. and lBO.--lil. and the crthe. ortho bron benxyl phenol from iso'--zosf The fraction from 203' up appeared to be di bonsyl oonponnd. This tins. however. the fraction from 198.- 803. came down as a crystalline solid which re- nninod fairly solid at room temperature. In an attenpt to further purify it it was redistillod with the corresponding fraction iron the next con- donoation. There were no solid products from the petro- loun ether extract distillation and it also was laid aside to be combined with corresponding frac- tions in the following condensation. Sixth condensation Ethyl ether extract 90' - 129' 13.: gms. iss' - 180' z. - iso' - iss‘ s.s - 19so - zoo’ is. - residue 80.? ' Petroleum other extroet eo' - 12s' is g... iss’ - 110' s s 110' - ise' si.s° 1se’ - up 1.30 The results here were very analogous to those of the preceding condensation. the sane fractions solidifying. A larger anount of charred material 3?. .__A.-.— was obtained. probably. the result of a small amount of mercury from the mechanical stirrer hav- ing worked down into the reaction minture of the flask. The presence of mercury seems to retard the reactive ability of the sodium phenolnto. Whether this is a catalytic or chemical reaction is not known but the fact remains that the yield of phenol in the presence of mercury is greatly re- duced. The four phenolic fractions 125° - 180: and 180° - 1’5: from the last two condensations were combined and distilled at 15 mm. The dietillsts up to 195° was taken off and then the fractions from 195° ~ 203° were added. on. majority of the compound came over from 196° - 198° and solidified when seeded with a crystal from the original 195'- IOI. fraction. Thirty grams of a white crystalline phenol were obtained which recrystallised from high test gasoline in small thick colorless plates hav- ing a melting point of {7° - 48: This yield rep- resents is: theoretical for the fifth condensatfibl and 132 for the sixth. 28. . .fl—‘_.‘_A_.l Analysis for bromine content was as follows: weight of Weight of 1 bromine theoretical sample bromine by analysis .2430 .0758 80.? 30.4 .8378 .07834 figg;gg_ 80.4 purg- 50 .(yo'f This is compound number two (11) and represents a 182 yield. It is 8‘ brem 1 hydroxy diphenyl methane. The phenolic compound from the earlier condon- sationo was placed in solution in petroleum ether and seeded with a crystal of the phenol just obtained. The resulting white flaky plates were filtered in the cold and dried between filter papers in the ice box. A yield of 12.2 grams was obtained with a m.p. of 44' to so! rive grams of this compound was re- crystallised slowly from gasoline and gave practi- cally a quantitative white plates melting that these two forms from a difference in of crystallisation. yield of heavy crystalline at 45' to s?! It would appear are interchangeable and result erystallising media and speed The petroleum ether extract fractions from ice. s. iso' were combined and distilled .e is mm. with 4: grams coming over between 184' - 100! \\\\ 29.§ This refused to solidify even when seeded with orthe brom benxyl phenyl other crystals. It was then re- distillod at 3 mm. pressure. Thirty seven grams came over at loo.--188. and solidified in the re- coiver as distilled. This material was recrystal- lised twice out of hot ethyl alcohol. to give a yield of 30 grams of the same other.obtainod in a previous run. (m.p. 84.--36°) III Aluminum chloride condensation. ,0" __0H JOILV OD: (flow/:59 O M 0&2; U * m .dSQ In the following condensation molar quan- tities of benxyl chloride and three molar quan- tities of phenol were placed in solution in petroleum ether and treated with } molar quan- tities of A101,. freshly distilled ortho brom benzyl chlo- ride and phenol were placed in solution in dry petroleum ether in a Jar. The Alcl3 was added over a period of two hours with efficient stirring. Care was exercised to keep the temperature of the reaction mixture down. This was accomplished. not by artificial cooling. but by a gradual addi- tion of the A101,. Iteno found that too efficient cooling was apt to spoil the run. in attempt was made to carry on a condensation at I. to 10‘ 0. lost of the phenol and benxyl chloride was re- coverod in this run and very little of the product obtained. A temperature from 20° - 80° seemed to give the maximum yield. After adding the A1013 the reaction mixture was stirred vigorously for two hours. Clouds of H01 were given off as the reaction took place. The mixture was then allowed to stand over night. The A161, complex molecule was then decomposed with a mixture of concentrated H01 and ice. and the resulting mixture treated with an excess of claisen’s alcoholic potash solution. This. as in the Claison condensation. rendered the phenolic compounds insoluble in petroleum ether and allowed the extraction of any other compounds present with this solvent. This extract use handled in the same fashion as that in the Claieen reaction. The other was driven off on a water bath and the re- maining oil fractionated under vacuum. After extracting with petroleum other. the mixture was acidified with ice and concentrated Eel. washed with water to remove the salt that was formed. and extracted with ethyl ether. The ethyl other solution of the ortho and para phenols was fractionated under vacuum. the other having first been renoved on water both. In the work of this experiment it was possible to separate the ortho from the para by pressing the mixture of oil and crystals result- ing from fractionation. between filter papers. The pars being crystalline was obtained in a fairly pure form and recrystallised. The oil was extracted from the filter papers used in pressing. and upos redistillatios also crystallised out and was later shows to be the ortho compound. Two runs using i nolar quantities or o-brel benxyl chloride were made with the following re- sults. Amounts used- phenol 141 grams 0 brom benxyl chloride 10: ' I 1101, 33 Results of fractionation or first run. Ethyl ether extract - at 15 mm. up to 18!. 75 grams ias'- 194’ 10 . iss‘ - zos' zo . zos' - sis’ is - sis' - sss‘ is - Charred saterial 88.6 ' Petroleum ether extract - 0 up to 160 iee' - iss' 155° - 195° 195° 9 up at 15 mm. 27.3 grams '24.s ' 2.9 ' 10.1 ' Results of fractionatios of second run. Ethyl other extract - at 15 me. up to 185° 155° - 194° 194° - 205° 205° - 215° 215° - 235' charred material 81.2 grams 7.8 ' 17.7 ' 16.6 ' 10.0 ' 41.9 ' Petroleum ether extract - 15 an. up to 1‘5. 165° - Les“ 0 18s - 195' 1". - up 10.3 grams 11.1 ' 0.8 ' 8.1 ' Purification and separation of fractions from A101: condossttios. The phenolic fractions in and around :00. became semi solids but it was considered best to purify further by distillation. Accordingly the fractions were redistilled as follows: The fractions from both condensatione fre- 105° to 194' were distilled at 10 mm. and frac- tions taken off up to 19': The 194. to 29., fractions were then added land the following fractions made; 19!. to 800: and 200° to 30‘: The 203’ to 21!0 fractions were then added to the distilling flask and fractions made from 204° - 201' and 207° - 2122 The final result of the fractionation is as fellows: ies° - 195° s.1 gran. in0 200° 10.7 - 2000 204‘ 15.s - 204° 201° 15.7 - 207. 21:. -10.s - 212° up 24.2 - at 15 In. All of the above solidified except ies’- ltl' fraction which remained an oil and that fraction above 212' which was an other seni- resinons oil. assumed to be the di benxyl sen- pound. The various solidified fractions were pressed between chilled filter papers and the oil . removed free them. then recrystallised. The result was 37} grass of the pars phenol. This was white is color. lee: noodles in form. had a b.p. of 201' to 108. at 15 In. and a n. p. of 71° . 7d: Parr bomb analysis of para compound is as follows: Weight of sample weight of bromine inronino Theoretical ; by analysis .8109 .08910 31.0 30.6 .8348 .07008 81.0 80.d This is conpound sunbor three (111) and rop- rooents 18 1 yield. This cowpound is 8' tron 4 hydroxy diphenyl nethano. The filter papers used is the removal of the oil were extracted with ethyl other. added to the fraction from lee. - 19s. and fractionated. This gave us about 10 grace of a white solid boiling at 19d. - 108' This was recrystallised free gas- oline and petroleum other to give a coupound very similar in appearance to our ortho compound. This compound had a Belting point of d). 0 ‘0. when crystallised from other and so. . ssi’ free case. line as conpared to that of ‘4. - dl‘ end 67. . ‘8' respectively shows by the ortho cosposed prepared by Olaison'a netted. The yield hero is 61 of theoretieal and is later proved to be eonpeuad number 11. The fractions from petroleum ether extract were redistilled is the same manuer with the following results. up to 140. 552 grams. 1oo° - 155' 10.7 - 155' - 1se' 29.9 . iea° - ioo° 15.: - 1oe° - up 4.4 - The fractions ion“ - 155° and 158’ - ise' solidified when seeded with a crystal of the knew: ether and upon recrystallisation from hot aleehel some 23 grams of the other melting at 34. - 8‘. were obtained. This is compound number one (I) and is a yield of 102. 37. IV. Proof of identity of the 2 hrs. bensyl phenyl other. is a check on the 2 bros benxyl phenyl other. a condensation in alcohol between the o bron benxyl chloride and phenol was made. Quantities need are HG“ equi nolar. 0H £19 O,L Pa ' H H (’41. 0H + *fié“) r Mad fix The phenol was put in solution in nethyl al- cohol and finally divided sodium was added slowly. This gave a clear syrupy nixture which was heated and stirred one hour at 130° and allowed to stand over night. The bonzyl chloride was then added thru the condenser and the mixture was stirred and heated to 130° for four hours. The remaining a1- cehol was then driven off on a water bath and the nixture then washed with water to remove the salt. It was then fractionated under vacuum. Quantities used in run. 12 grams phenol 25.7 ' o bron henzyl chloride 3. ' sodiun Results of fractionation. 8 mm. up to 185° 16 grams 39% 125' - ioz' . a gram. ios' - 15s“ ; ‘o . 1as° - isa’ ' 1 - ioe° - iso' s - iso’ - up deco-position The fractions fro- 152° . ll... 15" -1so2 and 158' - iso' solidified and were crystallised twice out of hot alcohol. The result was ll trans of the other. white and crystalline in fern. hav- in; melting point at 34° ~ set This 1. eenpeund nunber one (I) and represents a yield of £21. 4oi 7. Proof of identity of the 3' bron 8 hydrsny di- phenyl nethane (cospound ll). 0 Glaisen condensation was node between ortho. bron benxyl chloride and I. 4. di bren phenol. —aH CA 0” _ W! U m‘ I A? (h “533 " ° WC? Wu. H + "1“", ("I , ' 2am JC f. '_ -/“ .Léi‘g m /t/elL,{ Q / The quantities used were as follows. 50 grams 2.4. di hrom phenol d2 ' o bron benzyl chloride d.C ' sodium This condensation was run in the usual manner with the following results. Ethyl ether extract at 3 mm. up to 800. 33 grams zoo' - 220' e - sso' - zooo s 0 350. - up (Charred) 15 0 The fraction up to 200‘ was found to he the unreactod phenol and the fraction 220o - sso' was mostly decomposition products. The fraction zoo' — 220° was rodistilled at 3 nu. to give 4 grams of the 2, 4 di bron, 0 erthe hron benzyl phenol with a boiling point of 804’ - 8002 This did not solidify on long standing. In an attempt to produce crystallisation. this phenol was seeded with a enall crystal of 8. e. o0 tri bron a hydroxy di phenyl nethano. It was hoped that the similarity of the compounds night cause / 3 J crystallisation. Such was the case.for the 1. ’h- f 2’ tri bron ; hydroxy di phenyl nethano solidi- 21;; over night. This compound was recrystallised to give a yield of 3} grams of fine white crystal- line phenol. m.p. 41%. - 42%: Parr sulphur bomb analysis. fight. of fight. of Z Bron by 1 Bron by Sanple bronine analysis calculation .2007 .llell 85.! 37.1 This is compound number four (11). Petroleum ether extract. 3 an. up to 185° 80.8 grams e . 188 ~ 180 2.7 0 ' o 180 - 300 8.4 ' soo' — up ' 2.: ' The fraction up to 128. was assumed to be principally o-bron benxyl chloride. That fron lie. - 180' was found to he a nixture of e-brcn benxyl chloride and 8 bron hensyl I. d. di bron phenyl ether. That fron ioo' - soo’ solidified ‘2 .‘| in the flask and was scanned to be the other. This fraction was redistilled and gave us six era-o boiling at 113° - 195‘ at a In. On the third crystallisation from hot ethyl alcohol this gave 4} grans of white noodles with a n.p. of so? - as: Parr analysis fellows. 'ght. of fight. of 1 hr. by 1 hr. by danple bronine analysis calculation .8138 .121s 57.8. 37.1 This is eenpound number five (Y). Direct bromination of 2’ bron 2 hydroxy di- phenyl nethane. 0H 0H 0’1 5 in § The usual procedure for the A1013 condensa- tion was here followed. Quantities used were as follows. to grans 8. 6. di bron phenol zs.e ' e bron bensyl chloride s.e ' slei, In this run equi nolar quantities were used instead of the usual excess of the phenol since there was no possibility of the fornation of the di benxyl phenol due to the presence of the two brenina atoms in the s. 4. position. The result of the fractionation of the ethyl ether extract was as follows. I II. up to 300. la grans. soo' — sos’ .1 . soa’ - zos' s.s . 309. - up 4.0 ' charred naterial 6.8 ' 4m The fraction up to 200' was nostly the un- roaoted t. 0. di bron phenol. Tron 800' to 203' was a nixture of 8. e di bran phenol and 8' 3. d. tri bren d hydroxy di phenyl nothaae. The frac- tion fron 203° - 309° solidified and was accused to be the conpeund desired. This was pressed be- tween filter papers end finally recrystallised 4 M 3,5;2’ twice fron ligroin to give d.2 grans of 2. di A%¢,&umuaah Puzgfiul . . bren d o-bron onsyl phenol n.p. 18 - so. This is cenpound nunbor six (VI). Parr bonb analysis. 'ght. of Ight. of z sr.by : Br. sanple bromine analysis theoretical .8080 .1187! .7.d [7.1 .8087 .11700 56., 57.1 “”0 57-r{ Insufficient material resulted fron the petroleum ether extract to be of value. Direct bronination of the 2' bron d hydrexy di phenyl nothano. -0 ’0“ nzd\fi» O. m’lb‘v”? I r ”Hm _, ”an- 2&3 2L} rive grans of the para conpound were dissolved in ehlorcform and treated with seven grams bronine in chloroforn. Addition was nado over period of an 47. hour; to keep the tonporatnre down. and the nixture was allowed to stand over night. then evolution of the E It tunes had ceased the oonponnd was placed on the water hath and the chloroforn driven off. It did not solidify. It was distilled eoning ever at sos’ - see! It still did not solidify. It was rehroninated in chloroforn and immediately started to for. crystals around the edge of the beaker. After the chloroform was again driven off. it cane down in a solid uses which on the second crystal- lisation tron gasoline gave 3.. grans of long yellow needles. n.p. 78' - 802 this is also eon- ponnd VI. 48. VII. Preparation of esters. The method followed is below (Stewart and Branch, organic analysis). 'Diesslve 8 grams of the substance in 3 grans of_dry pyridine, add 1 gran beasoyl chloride and allow it to stand over night. Add an equal volnno of water slowly. cooling if necessary. and shake ‘ the mixture until there is no detectable odor oi honneyl chloride. Pour the mixture into cold dilute sulphuric acid. extract it with other} wash the other with cold dilute aodiun carbonate. and distill off the other. The ester is crystallised out of hot al- oohol.‘ This procedure was modified to the extent of using 5 grams of the phonol in starting and pro- portionately larger amounts of pyridine and bensoyl chloride. The following esters were node. 0- 6"ch5 E H n. n.p. . se' - eo' nonseyl ester or z' brom.z hydroxy di phenyl asthane. 49. m. p. . 64° - so‘ Bsaeeyl ester of 3' hrom 4 hydroxy di phenyl methane. (/0. yc‘chS M“ nope ~;<::::> Benxeyl ester of 3' 3. a. tri brom 4 hydroxy di- (did not solidity) phenyl methane. leheao of condensation. 6/4/30» In?) [0m O-M(NO) a.- c .— u 0' a (D By Jr e 1 - all an») file], ml: “tee" .9 ., MP. "373' 9-: cf!" N M'TITI'ITIQII'IILEJMRILiiflflflffllfil'lflfliflflfijmlfl”s