THE PREPARATION AND BENZYLATION or ' ORTHD-BROMOPHENOL THESIS FUR THE DEGREE OF M. S. Murel M. Ballard 1932 THE PIE-PABAT I O}! Al‘ID BESZYIAT I 011 OF 0- 3B OEOPIE; 30L. TEL-d ILL-261‘; 1x131)... ’3:- JD xBELmtl-‘IOZ; 0P O.d£~\).u\3; 1;»;1'JL by 2217131 n1. BALL}. 1.1) SUL 'I1'1'l' 1'0 1'31. FACULTY OF KISS-E GKE81'A1'13 COILLSE 0P £61.1C811‘J11; A}. D AP ‘LL DSL. 11‘1“. A3 I'm-3L3. FILE $13.53? 011‘ 231"}; Id..(;IJII’J.1£..1-'TES OF THE D.- £115.33 0 ' Lm"33'1'1.1-. 19' SCLQIICI‘L‘. .~ “2- 1A0f~-, U AI-L'J 01"“! 3m: WRITE?» name To man-.333 ms 811503-13 ugzmcunon 10 m. a. c. Husrox. WHOSE 1mm Assxsrm m ADVICE ms mm Possrm m cogmrrou or rm won ovum» IN THIS THESIS. 33 1605 C HISTORICAL DAIA OKTEETS- Preparation: of o-Brononhenol - - - - - - - - - Condensationa of’Pheno DISCUSSIOH 11c Compounds - - - - - - In. Bromination of Phenol - - - - - - - - - - - Theories involved in the Claiaen Condensation EXPEBIIEHIAL BAIL The Preparation of o-Bromophenol - - - - - - - The Hodlfled Method for Preparing o-Bromaphenol Th0 fibthod of E. H3203 n-nthodokrmgi udmtmu-------- The Emulation of o-Bromophenol - .. - - - - - Various Derivatives of achroma.6-benzy1 Phenol m1)“: of the Various Propel-guan- .3 . - . - M.------------------- Disgru- 02 Reactions 1‘ 1? 18 3? 3888333 HISTORICKL DATA. PREPARATIOE’S 0P OofiiOIJDPELI‘S'OL. my ineteneee er the preperetion of e-bronophenel eppeer in the literetm. The following ie e brief reeule ef the lethede thet here been reported. the eerlieet reeerded eerk en the preperetion er ochre-e- phenel 1e thet of Hebner end Brenten in 1873. (Ber. 6. 171). my report heving obtained the «mound. elen; with pone-.- phenel. by the direct hreeinetien of phenol dieeelved in fleeiel eoetie eeid. The reenlte er Hnbner end Brenton. heeever. were denied by Gordon. (Free. 1891. 64). who repeeted their eerk end eere led to the eenelneioe thet “the product or thie nethed ie el-eet atirely p-brenephenol'. rue nethod wee further inveetigeted by meldele end streettield. (J. Chen. See. London 73. 681. 1893). the veri- tied the reenlte of Butler end Breme. In 1884. Lellleee end Greth-enn. (Ber. 17. 2726). pre- pered the eeepound free berm. 3cm beneoie eeid. They heeted the eeid fer the te .1: m:- et 13o'c.. eds-hoe dicide eplittie; of: tree the eerberyl group end yielding e-hrenephenel. my reperted eetieteetory yielde by the u. e! the method. I . - Pitti‘ end Maser. (Ber. e. 362). end eleo Keener. (Gene. cue. Itel. d. 388). reperted the preperetien {rel O-brene- elilile by dieeetieetion end enheeqnent deeempeeitien of the “will eelt 11th eater. In 1893. 3. Beret. (Ber. 27. £957). prepared e-breeoo M by the direet breninetien of phenol et high telperetere. he reported en elnoet quentitetiwe yield. Thie nethod will be dieeneeed in here detail later. In 1898. Heldole end Streatfield node the eonpotmd tre- e-elinephenol. by repleoin‘ the enino group with bromine by diesetinetion eeoording to the Sendneyer reaction. (3. Ellen. see. mm 73. 685). ‘ ‘ ' In 1909. Oberniller. (Ber. 42. em}. obtained o-brono- phenol elou with other produete. by brominetion of euli‘enie end eerbwlie eeide or phenol with e mixture or eodinn breuide end eodinn mobronite. He believed this to be e eniteble broninatin; egent oinoe it libereted bromine elowly ellowin‘ elow brominetion or the phenol. the tendency being to uintein e eonetent eupply or the eotive bromine. In 1910. Hello-en. (K. died. Wetteneeheppen 13. 476-8). ebteined pure o~bronophenol by the distillation of the dry pierete. thin nethed wne elee need by Rinkere in 1911. (Bee. new. Chin. 30. «400). In 1912. Dineiddie end Keene. (o. A. 6. 482).. bronineted phenol by eddies en meee er bromine to phenol dieeoleed in urine eelmte eneh ee ohlererorn. eerbon tetreehloride end eerbon dienltide. They obteined nixturee of none- end dibreno- phenole. . In 1922. H. aeinee. (J. Chen. See. 121. 281002813; c.» 17. 995). eerried out the direct broninetion of phenol in eerben tetrachloride end etndied the effeet or eddies eeter to the reeetion fixture. he found that the dry reagente gene ortho. pere. or 2.4-dibrenophenol. whereee the eddition er weter eeened to fewer the tornetion or the tribrono- eta-mun. The theory involved in thie method will be “owned to none extent leter. re 1925. Tekeci tee Knteni. (J. Phern. soc. Jepen on. 8d7-2523 c. A. 20. 2669). prepered o-ehlore- end e-breneo phenol by edding the halogen elowly. et reen tenperetnre. to e eelntien or pheneldienlfonie «no. They report very good yielde in the eeee or the ehlorine deriwetiwe. Apperently the yield wee eoneidereble lower when bromine wee need. Thin hotbed will be given in lore deteil later. 1- 1927. street the scum. (m. Soe. Chin. ea. ooo). inweetinted the direet broninetion of phenol dieeolwed in pyridine. they reported u—edfi yielde e! the erthe eonpeeed by thin nethed. the neet reeent report of the inweetigetien of the treat-tutu of phenol :- that or e. v. Lithoeheretow in 1929. (I. no... out. one. s... 61. 1019-1023; c. A. at. one). the nethod ie e unique one end neee ee the broninetin; egent. e We of poteeeien broeide end diehlorenree. Ilenebrene- deriwetiwee were obteined in elneet quentitetive yielde by Iain; Ieler quentitiee of phenol end poteeeinn bromide to helt neler qnentitiee of diehlorouree. Thie ie peeeible. einee one equinlent of diehleronree reeete with two eqniweo lente eat peteeeien bro-ide. liberetinc two equinlente er bro-inn. The profit of thin prooeee in e mixture of erthoo end pere-bre-ephenel which ere eepereted by freetionel dietilletion. COMBSA’IIOHS OF PHEHOLIC CCh’Z’OUHDS. alone 3. Paterno. (Gene. Chin. Itel. l. 166. 1872). firnt prepared‘beneyl phenol. there here been innueereble inmtigntionn concerning this end einiler typee of eendenc netionn ot’phenoln end.releted compounde. While it wonld.be inpreetieel to give e eonplete reenneof theee inventigetiene. the following in denigned to present e brief outline of the develop-eat of preeeednree end theoriee that eppeer to here e dietinet beering on the problem covered in thin thenin. Peterne brought ebeut the eondeneetien of phenol end beneyl ehleride through.the agency of nine chloride. Iran the Mt .2 thin reeotion he ieoleted . compound uieting no white needlee end ulting et si". which be “me to be beneyl phenol. He elee prepared.varioue derivetiwee of thin none-Id with e view to eetebliehing ite eonetitntion. In 1874. Peter-no end it. riieti. (om. Chin. Itel. a. mom. 851-254). reported the preperetion of other deri- wetiven ot’beneyl phenol en further attempts et identifi- eetien. In 1875. theee eene werkere prepared the name beneyl phone]. in n elightly different wey. fining bonnyl eleohol in- nteed et beeeyl chloride. end bringing ebout oondeneetien by the elininetion of water. They and e nirtnre of eulfiu-ie neid end eoetie' neid en e dehydreting ezent. In addition to tb mend previously obteined. there reeulted fr- thin hthed en oil whioh they unnamed to be en ieonerie beneyl phenol. :- 107e, Peterno the We (next. Chin. Ital. 8. M30 “nut ebont the eon. ation neinn nine tnrninre. III 1880. Perkine end Hedgiineon. (J. Chem. Soc. 724). propel-ed beneyl phenol by the oondeneetion of beneyl ohlo- rib end phenyl eoetete in eneline eolntion. Their eon- potted lelted et 80.081... end nee believed to be the pore Md. In 1882. Rennie. (J. Chen. See. 41. 220). cerried out e eeriee of inventigetione in which he identified the ery- etelliee compound melting et 84' no the pore ieomer and the eil ee the ertho leaner. In the ewe yeer. Leibnenn. (Ber. 15. 152). eooonpliehed the eule condeneetion in the presence of nine chloride. In 1833. Benzene. (Gm. Chin. Itel. 12. 505-511). brought eboot the oondeneetion by the use of magneeiun chloride. In the eev'oral yeare following these investigation. there were reported my oeeee of oondeneetione which ere ee remotely releted to the present problem ee not to require dieeneeion. Prebehly the meet eetiei‘eotory end eoet widely need lethed ei’ eondeneetion of phenolic oompounde with elkyl lelidee even ite development to the work er Cleieel. W et ite invertenee. it in given here “that in deteil. The following in e my et hie nethod no reported in 1323. (1.. Algow. Chen. 36. 478-479). The phenol. dieeolved in e Iolodieeooieting medial each on toluene. wee firet con. verted to the eedinn eelt by heating with metallic Indium. mu- thie reeotion wee oompleted. en am or eubetitnted elkyl helide wee introduced and the heeting continued. The product of this reaction one found to contain not only elkyleted phenol but nice elkyl phenyl other in varying mounts. Cleieen oopnreted these by first treating the mix-- ture with alcoholic potenh solution which dieeolwed the elkyleted phenole. The elkyl phenyl other was then ertrected with petroleum ether. The residue from thie who then treeted with hydrochloric eoid which egein liberated the phenole present. Theee were then extrected with ethyl ether. aleieen also carried out other important oondenentione. (All. 442. 210-245). The work or Claieen .111 be diecueecd in more detail later. In 1927. Bosch and Knoll. (her. 603. 2543-2357). reported work on the alkyl condeneation of enbetitnted phenele in which they indicate that the preaenee of elec- tro-negntiwe monoe on the nucleon of the phenol town the formation or alkyl phenyl other. while the presence of electro-poeitiwe groups favors the tormtion of the elhy- 1eted phenol. Another type of condenention which in of great impor- tance. especially since it has been enmloyed to n. conni- derable extent in this laboratory. in that brought ebout by the catelytic notion of eluninun chloride. Since. however. the work outlined in this theoie has not been particulerly concerned with the aluminum chloride condensation. it will not be diamond in great detail. Following 1. a brief mount of ite derolopnont. ‘ Kohl-en firet employed the method. (Ann. 33-34. 97-204. 1840). in the preparation of ethere from alcohols. In 1877. Priedel end Croft. to who: hue been given not of the credit for the develop-ant of the Ithod. re- ported e greet deal of work. (3111. Son. Chel. 2?. ‘8. mt. Bond. 84. 1392-1595). particularly on the epplicetion of thin proeeee to the condensation of eliphatie compounds. In 1.881. More and Ueith. (Ber. 17. 18?). applied the fithed to dramatic condensation» In 1916. Huston end Eriedemn. (J. Amer. Chen. see. to. 2327). need eluinun chloride to bring ebont the eondenee- ‘ tie- et benzene and benzyl elcohol to diphenylnethnne. In 1918. the one non. (J. Amer. Chen. see. eo. 785- 79:). carried out condensetione neing eeoondnry eleohele. In 1924. Baotou. (J. Amer Chen. Soc. «16. 2775-2779). reported the condemnation of phenol end beneyl alcohol to p-beneyl phenol through the nee of eluninun chloride. Min; the loot few yeere e. great deal of work he been done in thie leboratory on the elunim chloride eondoneetion on well do the Oleieon oondeneetien or honeyl ehleride end ite halogen derivetivee with phenol end releted phenolic ee-ponnde. Since it eould be ueeleee teettenpt e eelplete “or! of thie work. it in thought loot edvieeble to Unit the eeope oi’ thie paper to dete directly hen-in; on the problem et head. DISCUSSION. Tile. fliOAiI 3:105 03‘ PMGL. coneidornble time one spent in the development of the nethod for preparing o-‘oromophenol. not because nethode of properetion were looking. but became none of the aethodo already available cave ontinieo tory results for preparation on o well eoele in e. student laboratory. It was desired to provide 11 eimple. dependable. fairly efficient method for preparing o-‘orowophenol from easily obtainable materiele. With the exception of the method of heroic end that of rekui end mtmi. the methode of preparation already in non involve the use of expensive material: and are therefore mentiefnetory. The method of Hero}: and that of Takegi end Entani will be discussed in some detail later. The method with which this paper in chiefly concerned m first carried out by R. Dooeer in 1931 in this leboretory. ' It was adopted from the preparation 01 2.6-di’oromophenol. (F. a. Wield. 1950). which. in turn van adapted from the preparation of 2.6-dichlorophenol. iii. Tameka and K. Kuteni. Co A. 21o 2255). - It in n roll been principle of Organic Chemistry that the hydroxyl group on a. benzene nucleus tends to direct the whetitution of bromine to the ortho and pore. poei tione. The aeolumiem of the reaction involved in thin preparation in based on the blotting of the para position by e eodinn “female group. (-eoaone) . thus leaving only the ortho position to be filled. The preparation no originally carried out by Doeeer in thin leboretory ie repreeented by the following echo-u OH. OH so my to 100‘ a + HOB T 52 4 for 35 ’ mnutes sozon 0E one + 2 3.03 (to; £30211 7‘ 1. 2 HOE \\// * $020.3 SOZONB one 33?!‘ L ’ + d "7 SOZOHa SOZONa Olin ' on Br Br 1 3203:: ‘80,! Heist)!I ~ ’ ‘ § Enzso‘ 0 can. t 802033 Very good yields were reported for this method. On repitition of the work. however. an innumerable number of trial- feiled to duplicate the results of Hr Donner. the yield at the ortho compound being. in fact. very low. The prooeol invariably resulted in the formation of higher hrono derivatives along with a. terry roeidno. To explain this lionrepaney'it In. assumed.that some important o. .I"l ..l .u-l U 10 condition 01' the process no previously carried out had not been noticed or recorded. The negative‘roeulte 1e to 5. series of. modifications of the process «ed the development of 9. method which has given. eatiefectory reeulte that may be readily duplicated. Attention is called to the {not that in phenol there are three positions. (3. 4. and 6). in which bromine may be quite readily eu‘oetituted. In the ahove process. only one. the para or 4 poei tion. is blocked leaving the tro Ortho positions open. fimoretioully it may be possible to ' stop the reecti on at such a point that only one of the” open positions is filled. n’i th bromine. but this would neo- ceeearily be difficult and indepemhble. This is believed to account for the formtion of the higher bromine derive.- tivee. It scene mre reasonable to assume. as did rehgi and Retard. {page 3). that if two PUB-{E10330 he P8378 and one ortho. were blocked. the chances for obtaining the o- hromphenol would be considerably increased. Thus it seen-ed more edvieahle to tiret for: the 2.4-dieulfonic rather the: the ivmnoeulfonie 301 d. It in further believed that the thirty minutes heating on need in the above process in not sufficient for the [ul- tonation of the phenol. this idea in supported by Tannin and Extent. who originally marked on the problem. The! hosted the reaction mixture for three hours to omrplote the enl- fonat-i on. The literature seems to indicate a number of conflict- in; opinion. in regard to haicgenetion. Magi and Mimi 11 club to hove obtdincd utiofoetory rcoulto by hroninnting the phonoldioultonic ccid directly. According to Bette and W. (J. Ann. Chen. Soc. 43. 505. 1921). chlorine. hroninc end in cone ccccc iodine. hoe been denonotrotcd to roplooc the cultonic ocid group. (-30:03). with the pre- diction of orcnatic halogen derivativco. They found thct frequently hclcgcno not only replaced the oulfonic ocid troupe. out that nonolly lore hologeno entered the ring Iith the formation of higher halogen derivetivcc. Thin they believed to be c good general method for the preparation of meson derivativec of phenolic compoundo oincc they found that replacement of onlfonic ccid group- by bromine tokco plccc readily ct ordinary tcnperetnrco in the cm of commando hevin; one or me hydroxyl groupo attached to the nuclear. If the interpretation of Dattc end Shoo-1k ore cor- rect. it nee-Io that 1'3in and Kutcni have detected their con mono in attempting to block the 2 end 4 pooitionc of phenol with cultcnic cold groupo. The otctenent of Dotto and flood! that “when bromine in flood in onoll quantitieo. only o pertiol detach-cot of the cultonic group oeonro one o hrcnocnltonic ocid io pro- «need" and that 'rcploec-ent ot the onltonio group by holo- ulo tokeo ploec noro coolly in the once of nono- then vith di- or trienlfooic ecid dcrivetivcc'. lcovoo cone poooibi- lity of the truth of the ocounptiono of retest end Eutcni. The writer ogreeo in port vith both of there vim but not in entirety with either. It in believed that the 12 evideuee indicated in the morinentel port of thie paper rill weeent acre or leee definite vieee in regard to thie die- eceelent. Bette and Bhonlik eleo etete thet 'inetead of free bre- Iine. it hee been found that e mixture of alkali bromide end “oute'. providee e better brominating agent. Thin ie in egreenent eith Oberniller. (page 2). who need I. mixture ef eodiu bromide and eodiun hypobronite. The theory involved in this proeeednre tee eetiefnetorily explained by B. Beinee. (me 2). Uh. etudied the effect of the eddition of voter to the broninetion fixture. Hie explanation eeeulee thet the _ elee reaction betveen dry phenol and dry braille ie one of direct lubetitution only. while in the presence of voter it ie one of addition. The bromine reeete with the voter preeent forming 303:. which. he believed. route in the folleving OH 80' Jr Addition of e loleoule of £03: to followd by the eplitting eff of e. uoleonle of voter leaving the bromineted product. We view wee confirmed by the direct eetien of 1103: on phenol and further eupperted by the feet thnt broninetien ie reterded by eonditione that tend to hinder the fornetion ef 1103!. N In the nethod need by Donner. the temperature of the reeetion mixture during hydrolyeie of the enlfonie eeid to , e-bronophenol. '8. minteined at 175°. According to 15 m and tilted. (J. Phnrl. Soc. Japan 541. 196. 1927). whe flret need thie proceednre. the yield ie mach better if tho telnernture of the reaction et thie point in rained to 100.- 210.. The effect of thie change will be diecueeed in the experimental part of thie paper: 14 THEOML‘S IEVGLVhD III TEE. CMISBH 6333211352103. The condeneati on of phenol and. benzyl chloride accord. in; to the nethod of Claieen nay berepreeented by the fol- lewin; eohema Obviously. the eimleet eouree of the reaction would reeult in the fomtion of A. phenyl benayl other. Thin product was expected by Claim and no found to be pree- tieally the only product when the reaction was carried out in a dieeooiatinc mediu- euch ea nethyl alcohol. When the reaction wee carried out in non-dieoocioting lediun. 15 however. it woe found that along with the other no ob- tained a ooneidcrable amount of o-benzyl phenol. The above echo. aeoounte for thie by oncoming that the beneyl chlo- rideaddeontethephenolintheunnerehown.ecdiu .ehletide then eplite off. leaving a compound of quinonio Me which enoliaee. for-ins the ortho eubetiteted phenol. Claieen baaed thie theory of the nechanien of thie reaction on the theory propoeed by Hicheal. (I. Pr. 3?. tag co. 189). regarding the reaction between eilwer cyanide and lethyl iodide. which he believed proceeded according to the following equations A. - c + I - m u: q» 3’ g! 531—» .gocx, ‘9 g-cns claieee laintained that maturated coupe eubetitnte in the ring more readily than eaturated coupe and aloe that the tendeney toward ring alkylatiu inereaeed with the “Mutation of alkyl coupe on the ring. Glaieen did not indicate the formation of a p-benayl derivative in hie preparation. however. on recent werhere have reported owideneee ef pare enbetitntion. It ie diffi- cult to explain para eubetitntion on the baeie of the above theory. ' In 1926. K. W... (Ghee. zentr. 1. zen-2m). attewted to explain the ring alkylation noted in connection with the Claieen reaction. Be euggcetcd the following three poeeibilitiee. 1. The fernation of addition producte and the cubee- enent eplitting off of ealt ae indicated by Claieen. 16 2. Oxygen alkylation. followed by rearrangement of the molecule. 3. The «motion of the metal and halogen an a hotel- ”. halide. leaving a free elkyl radical and a free cool radical. ' D, ,’O -H H .- _ 4H ' 7 The two radicale then combine to for: the alkylated phenol. The first hypotheeie ie the one noet generally accept- ted. It ie rather difficult to postulate rearrange-ant in one iodine and not in another. which would make the eeoond theory econ doubtful. The third theory ie fairly reaconable but none lcee probable than the theory ae firct advanced by Claiecn. The preeent preblcn involvee the bencylation of e-brono- phcnol according to the neth of Claiccn. From the find- inge of Bunch and Knoll. (page 6). it wee cucpeotcd that the preconoc of bro-inc attached to the nuclcue would favor the forution of the phenyl bencyl other. l? STATBZEIIT OF THE P3033131 The problem outlined in thie thesie may be considered an ccneicting of the following four partez l. The development of a eaticfaetory method of preparation of «brmphencl froze caeily obtainable mteriale. 2. The benaylation of the e-bronophenol according to the method of Olaiecn. 3. The preparation of various derivativec from the ben- cylate d e-br onophcnol. «t. The analyeie of the derivatives: prepared for the pur- poec of identification. WIREFBAL DATA TIE PEEPARATIOH OF O’BROEOPHEKOL no preparation of e-hronophenol according to the le- thod of honor wee firet carried out neing one fourth nelar quantitiee of reagente. 2d crane of phenol and 30 crane.“ alight emoeee ever theoretical). of eulfurio acid were bated on the eteal bath for thirty ninetee to for. p-phenelo elitenio acid. The mixture wae then cooled and made alka- line with 501 eodill ludrexide eolution. cooling. 1'. the eeoled Iixture no then added slowly. 40.5 arm of bruine Ihile linking. After broninaticn. the lixture wae transferred to a fleet arranged for etean dietillaticn. The mixture wae then etean dietille'd to remove an: tribronephenol that had been for-ed in the reaction. During the etean dietillation. the fleet containing the reaction mixture was heated in an .11 bath a a temperature .: 125°-1eo°. When all the tribronophenol had been renewed. the nix- tere wee cooled and acidified with concentrated enlfnrie acid. Enough acid wee added to make the eolntioe about 80% told. steam distillation wee again carried out while heating the reaction mixture at rev-175'. do the enlfonio eeid hydrolyzed. the broninated phenol woe liberated and panned ever with the eteefl. When no more oil distilled over the dietillation wee etopped. The oil in the distillate was then extracted with ethyl ether. the ether evaporated off and the residue dietillod. The following fractions were obtained: 180' . 194‘ - - - - lo crane. 19d°0200.9--- Zane. 200.0215°-~-- 5am. 315‘-235°---- agrane. 255‘ - 255° - - - - 10 gram. Pure o-broxnophenol boile at 195° at fioepheric pree- eure. The fraction boiling at 194°..ng wee aeeumed to he Ioetly the deeired compound. Throughout the euboequent ex- perilente thie ealoe fraction was caved and weighed. than furniehing a mm of comparing the yielde ee obtained in the varioue triale. he may be eeen from the above figural. there nae practically no yield of the e-hromophenol. The rather large fraction from lSO‘olDd' wee undoubtedly one obliged phenol. The large higher boiling fractione were likely higher bromine derivatives. the preparation eae repeated many time ueing the cane neonate of lateriale and following the directione ae lleeely ee peeeible. It hae not been eoneidered neeceeeary to tabe- late the reeulte tron all of theee triala. but einply to etete that. in general. they were in oloee agreement with theee obtained in the first run. and in no once one there enough of the deeired eonpound to be called a yield. It rather represented nerely the paeeing free one fraction to the nut. After ceneietent failures to obtain e-bronophencl by thie preeeednre. it became evident that the method vae at fault. Undoubtedly. lone important condition for carrying out the reaction had not been obeerved nor recorded when the lethod wee firet carried out. he a reenlt of thie conelueion. the neth was carefully etudied with a view to locate possible difficultiee. The correction of these difficultiee required a long eeriee of triele of modification of the method. Biting the deve- lopnent of the rarioue modifications. the name general ' prooeednre wae followed. attempting to etudy and drew the proper eololneione concerning each of the modification- oarried out. ' The firet difficulty obeerved was concerned with the eodiun ealt of the phenoleulfonie acid. To do thie. 50% eodinl hydroxide eolution had been need. Thie made a colu- tion eo concentrated that during hrondnation the reaction mixture eolidified and thue prevented thorough mixing. It lewd reasonable that thin should have come effect In the reeulte. The preeeednre wee then carried out in the eon way as before but using 40% eodium hydroxide eolution. since the reaction mixture etill eolidified during bromination. ‘ thie run wee not duplicated. The final dietilletion of the product eeened to chew no change. 35% eodiuze hydroxide wee uecd next. Again. einoe the nixture eolidified during breminetion. thie wee not en- plioeted. Again. the final reeulte chewed little change. 30% eediun hydroxide eolution wee next ueed. Thie tine the mixture did not eolidify during broadnatice and the material was mixed thoroughly. 0!: dietillnticn of the final product. the following fractions were obtained: 130° . 194' . . - - 11 grams. iu°czoo'---- Sam. 21 200° - 210° - - - - 6 grams. 215° - 235' - - - . 1 grams. 235‘ - 255° - - - - 12 arena. .8. duplicate trial gave the following results which check fairly'wellz 13o“ - 194° . - - - 10 grams. 194' - 200° - - - - 5 grams. 200° - 215‘ - - - - 6 grams. 215’ - 235° - - — - 6 grams. 235' - 255' - - - - 11 grams. in may be ecen. the results of this change show an increase in the fraction representing oebromophenol. The preparation wee carried out using 20% and 10% cole- tione of eodimn hydroxide. respectively. with the following reeulte in the final distillation: eoznaoa 130° - 19¢° - - - - 10 grams. 194° - 200' . - - - 4 grams. 200' - 215° . - - - 5 grams. 215°- 235° - - - - 0 grams. 235. . 255° - - - - 12 grams. 10% noon . 180’ - 194° - - - - 10 grams. 104° - 200° - ~ - - 1 gram 0 200° - 215° «- - - - 4 grams. 210’ . 235‘ - - - - a groan. 235°‘- 255° - - - — 14 grams. 22 When using the 10;?) solution the yield dropped so low that it one not eonsidered necessary to run a duplioste on it. A duplicate us run vith the 20} solution with results practically identienl with those ohm above. The results shun from changing the concentration of the sodiun hydroxide Justify rather definite e‘elusions. Apparently an increase in the amount or water present during the reaction tends to sat down the yield of e-bronophenol. increasing the amount or higher bromine derivatives. This is in accord with the rim of H Baines. (peas 2).. the advantage. however. in being able to thoroughly mix the reagents during bronination. soeounts for the higher yield of e—hrolophenol then using the 305 sodinn hydroxide. 011 the basis of the above eonelusions. 30-5 sodiu- lu- dreaide solution us need in all subsequent runs. He- this point on. s neehanieal stirrer was used «hiring the addition of the sediun hydroxide and bromine. As was stated in the discussion. (page 10). it seened legiesl to expect a greater yield of e-‘orolophenol it two rather than only one or the three open positions of phenol were bleeked. The amount of sulfurie seid used in the pre- paration up to this point was only slightly sore than the theoretiesl amount required for s nonmlfonie aeid. With the idea in mind of bleekinc tee of the poeitions. the pore end one erths. by toning aucphenoldisnlfonie acid. a series or trials of the preparstion were carried out. increasing the quantity of sultnrio acid by usrying amounts. The preparation was carried out using 24 grains of phenol together with 50 grams. 90 grams and 120 grams of sulfuric acid respectively. In other respects the condition. of the proceedure were kept the name an before. using. of course. 301 eodium.hydrozide for the fornetion of the sol- fonate. Duplicatee were run on each.of these trials. The followin¢:reprooents the results fren.fine1 distillation of products: 60 grams of 8280‘ #1. £2. 120° - 194° ~ - - 8 grams 8 green. 104' - 200° - - - 2 grams 7 grams. 200o - 215._- - - 6 grams 5 creme. 215' - 225° - - - 5 grams 5 grana. 255' - 255° - - - 7 grams 2 grams. 90 arena of 3280‘ 130‘ - 104° - - . 7 grams 7 graze. 191° . 200° - - - 9 grams 0 grams. 200° - 215° - - - 5 grams 5 creme. 215° - 235° - - - 3 graze 3 grams. 255° - 255° - - - 7 gran: 8 grams. 120 grams of 32304 100° a 194° - - - 7 stone 7 grams. 19" - 200° - - - 7 grams 5 grams. 200° - 215° - ~ - 5 grams 5 grams. 215° - 235° - - . 5 grams 6 grams. 235° . 253° ~ - - 8 gnome 3 grams. From the above figures it may be seen that an increase in the yield of o‘brozophenol resulted fron.ineroaein¢ the assent of sulfuric aoid need. up to a certain point. 390 arena of H250‘ to 24 gram; ofphencl). which doubtless represented the blocking of two positions. Kore than that amount of sulfuric acid probably resulted in the foreation of a trisuli'onio acid and. the blocking of all three poni- tions. which would not permit any brominotion. Thin it in- dicated by the fall in yield observed when 120 grams of sulfuric acid were need. The large exceee of sulfuric eeid. (three and one half moles of 141230“ to one mole of phenol). ehioh soared to give the best results was come-what ourprie- ins. It in assumed that this much exceu is necessary in order to maintain the proper equilibrium between the 8111- . {uric acid and phenol and the phenoldieulfonio acid. In the trials which followed. phenol and sulfuric acid were need in the ratio of 24 arena of phenol to 90 arm of 1580‘. The next modification had to do with the time required for formation of the eulronic acid. to was stated in the discussion. Ianaie and Katmai heated for three hour- et 100.. it eppeared that tidrty minutco heating was incuti'ioient and left a rather large amount of unchanged phenol. In order to determine the optimum length of tine for producing the anionic acid. a. ocriee of trials were carried out twins the same amounts of mteriefils as in the proceeding rune but heating tor varying lengths of time. For duplioete triels eere run. heating for one. two. three and four honre mpeotively. on the steam bath. The following is n to“. lotion of the results oi‘ distillation 01" the final product in each coco: 0-0 hour boating i1. #2. 100° 9 190° - - - - 7 gr...- 7 grams. 19¢ . 200° . ~ - . 9 gram. 10 grams. 200° - 215° - - - - 5 grnnn 4 grams. 21.5»o . 235 - - . . t 330:. 0 grunt. 1". hours heating 100° - 194' . - . - 6 grant 6 grams. 194 .2oo°..-. naturally-m. 200' - 210 - - - - 4 gram: 3 grams. 215° . 235 - - - .‘ 4 gram. 4 grams. 235° - 255° - - - - 0 grams 0 grams. 100° - 104° - - - - 0 grant 0 grant. 190° . 200° . - - - 13 crun- 12 stain. 200° - 215° - - - . 3 grului 0 art-O. ”5.08350-000 Sal-.4318“. 3359 . 255° 9 . - . 6 grunt 6 arm-I. “muting 180’ . 19" - - . . G grun- 6 gr...» 104° - 200° - - - . 13 gran. 13 granu. 300° . 215°~~ - - - s.¢zano 3 grams. m°~230°~-~§ Gum 6pm. Observation of the above figures indicate. an increase. in the yield of the dented product as the tine of heating :- 1mmd up to three hours. Heating for 0 longer period 26 of tine did not seen to affect the yield. 011 the umtion that the disuli‘onio mo given the beat :1.“ of ochre-o- m1. it appears that about three houre heating at 100° is moot effective in converting the phenol and sulfur-is sold to the phenoldisulfonis acid. In the following trials. three hour periods were need for the formation of the ell- fonie sold. In sash preparation up to this point there had been obtained. is the first stea- distillation. considerable quantities of tri‘oronophenol. It ens believed that if so.- thinc scald be dono to prevent the formation of tribe‘s-e- phenol. the yield of the owthe mound night be corres- yendincly increased. The folloein; reasoning was applied to the problem airing bromination by substitution. one mole of brains produces. along with the brouinated product. one mole of hydrobronio acid. The hydrobroaio acid liberated during the broninstion of phenol should be expected to react with th sulfonates present in the reaction mixture. oonvertil; tb sodium sulfonate group to the salfonie acid group. Aeesrdisc to Dstta and Bhounil. (page ll). the sulfonis acid group is readily replaced by halogens. while it is believed that the sedan sulfonate group is not so replaced. 11’. then. th already brominatoé phonol‘has one or both of its sodiu- silo locate groups converted to sulfonio acid groups. and these are readily reylaoed by bromine. it is easy to account for the formation of higher bromine derivatives. In other nerds. if the mebrono compound is desired. and if the sulfonio 2? acid group is easily replaced by broninc while the soditn salfonate group is not. than the sinple neutralization of the reaction nixtnro before bronination is insufficient. In order to naintain the blocking effect of the sodinn enl- feasts group. there met be added to the phenoldisulfcnie acid enough sodinn hydruide to convert all the sulfonic acid groups to snlfenato groups. all the excess sulfuric acid to sodium sulfate. all the phenolic groups to phenolate groups and all the hydrogen bronide liberated during the reaction to sodi- bro-ido. this excess alkali should not interfere in any way with the bronination since alkaline hypobro-its solution is recognised to be a good bro-lasting agent. ‘ The amount of sodiun warme- to be added to on. reaction nixture was calculated in the following way. On the basis of nolar quantities. one nolc oyphoel. when snlfonatod with three and one half nolcs of sulfuric acid. (the amount previously deter-iced by experinent to be neat satisfactory). should yield one ncle of phonoldisnlfonic acid and leave an excess of one and one half noles of col- faric acid. Also. during bronination. one mole of hydrogen bromide is liberated. Three nolcs of sodiun hydroxide are required to replace the three ionisablo hydrogons .r the phenoldisulfonic acid. three to neutralise the excess enl- fnrio acid. and one to neutralise the hydrogen bromide. This lakes a total of seven noles of sodiu- hydrcxide per hole of phenol. or. one and three fourths Iolcs for a no fsuth nelar run. 0n the basis of this reasoning. the preparation was carried out using the cans quantities of phenol and sulfuric acid and foraing the sulfcnic acid as before. This nixturo was then lads alkaline with 75 grams of sodium hydroxide. (a slight excess over one and three fourthe holes. to allow for inoculate formation of the disulfonic acid). discoltd is 118 cc. of water. Bronination was carried out as before. when the nirture was steandistillcd to resove tribronophenol. it was noted that not any appeared. whereas it had appeared in varying ancunts during previous runs. rinal distillation of the product gave the following fractions: lBO‘elN°---- egress. 10c°~200'----icgrm. coo°-zu°---- agrans. 215'-2oo'---~ agrsns. 235.4255°---- Ogre-s. These results were very satisfactory and appeared to bear out the reasoning. The writer omiders this as possibly the lost significant point in regard to the various ddifi- caticss of the preceedure. It not cnly strengthened the belief in the blocking power of the sediun culfonate group. but raised oonsidcrabldojflfit to the advisability of broninating the sulfonic acid directlle (ram: and Kutani). or of replacing sulfonio acid groups with an alkaline brcninating agent. (Bette and Bhounik). A very interesting phenomenon in connection with this proeoodnro was the evidence of a color reaction during the addition of the codius hydroxide. is the excess alkali was 29 added. there developed a pink color in the solution which disappeared abruptly. almost simultaneous with the addition of the last few cc. of the calculated amount of base. Ho attempt was made to explain this. and though it seemed to have no further significance. it furnished an almost infal- lible means of determining the right exceos of base without calculation. A number of trials were lads of this proceedurc in order to verify the reeults obtained in the first run. Though it seem unnecessary to record here all the figures obtained. it maybe stated while in one or two caees the yield of o-bronophencl was a little low. in general. it was in close agreement with'that shown above. The next modification of the proeecdure had to do with the tomcraturs of the reaction nixture during the hydro- lysis of the sulfuric acid to bronophenol. The change was lads after a review of the work of Tanaki and Entani. (page 13). who carried out the process at 175° but stated that the yield could be increaeed if the temperature of the reaction uixturc was raised to 200'.210°. 0n the basis of this information. a trial was run. using the method pre- viously described only carrying out the hydrolysis of the eulfcnio acid at 200°oaio'. The following tabulation of the results of this trial show an increase in the total bro- ainatod product and a corresponding slight increase in the fraction taken as o-brcmophenolt 1eo'-194°---- 5grnlls. 1cc'-2oo°----1c¢rm. zoo'-215°~--- barons. 215'-255’---- dgrams. 235' - 255’ - - - - 3 grams. Several repdtiticns of this proceedure verified the above results. Apparently this nodification did not in. crease the relative amount of o-hrcnophencl in the reaction mixture but brought about the increase in the final yield by allowing a more perfect hydrolysis of the brominated phenolsulfonis acid. This nodification was carried out in all subeequent proceedures. Throughout the work thus far described the thought was held that anything that mam he done to make more efficient the conversion of phenol to phenoldisulfonic acid would correspondingly increase the yield of o-bromophenol. with this in nind it was believed that stirring during the heat- ing of the sulfuric acid and phenol night result in nere smlete eulfonation. or at least out down the tine noose- sary for the maxim reaction. “to study the effect of this proceedure. a seried of duplicate runs of the preparation were carried out. stir- ring while heating the reaction nixture on a boiling water bath for one. two. three and four hour periods respectively. In other respects the method was carried cut as previously found to be lost satisfactory. Following is a tabulation of the reeults of final distillation of the various products: One hour heating #1. #2. 180°ol§4.---- agrams agrane. lfl‘ozoo'oo--lOgranlegrans. 31 800°~2l§°---- Barons tgrans. 215° - 235° - - -’- e-eran. 4 crane. 235° - 255° . - - . 11 grams 12 grams. res hours heating. ieo' - 194° - - - - 4 grass 4 grams. 194’ - zoo“ - - - - 15 green in grass. -zoo'. 215° . - - . d crane 5 crane. 215' - 255’ - . - - 5 grams d grams. 855’ . 255’ - - 9 - 6 grams 6 grams. Three hours heating ieo' - 194° - - - ~ 3 crane e arena. 194' . 200’ . - - - 19 gr... lOgrans. zoo' - 215° - - - - a green a crane. are“ - 255' - - - - 3 grams t grams. 235‘ - 255° - - - e 5 crane 6 grams. Four "hours heating 100° - 19d“ - - - - d grams 4 grans._ iot’ - 200' - - - - is crane 18 areas. 200' . 215' - - - - 2 gram. 2 grams. 215' - 235° - - - - e gram. 5 grams. 235’ - 255' - - - - 5 grams 6 grams. The above figures satisfactorily bear out the reason- ing. It was shown that stirring and heating for two hour. produced.praotically the sane yield as heating alone for three hours. It was also shown. however. that stirring and 52 heating for three hours resulted in an increase in yield. the sons proceedure carried out for a period longer than three hours seemed to be of no advantage. ' Up to this point no mention has been made concerning the temperature during bronination. It sealed possible that this night have acne bearing on the results of the prepa- ration. Ordinarily the brondnation was carried out on the oooled.ndxture but no attempt was made to maintain a defi- nite temperature. During this prooeedure the temperature usually rose to about d5'-50'. To determine the effect of tenperature on the bronination a series of duplicate trials were run. By stirring with the flask containing the reaction nixture innersed in a water bath. the temperatures in three different cases were naintained at 20.-25’. d0’-d5. and so'.as° respectively. The following results were obtained on distillation of the final product: so‘bze° #1. #2. 1ec‘ . 194° - - - - 5 grams 5 grain. 194'.2oo°o--.1e¢rm11¢rm. eoo°¥215°---- agrans agrans. 215° - 235° - - - - 3 grams 4 grams. 855.0255°o--- egress Ggrens. 1eo’-19t'--.- agrees agrans. 194‘ - 200° - - ~ 13 grams 19 grams. 200'-215°---- egress 5grens. 215' - 235' - - - - d 5.... t grams. 255 o255°---- Ggrans ogre-s. 180 -lOd‘---- dgrams 4grans. 194'- 200' - - - - 15 grams 14 grams. zoo'-215'---- 5gre1ns ogre... 215'o255'---- 5grans 4grams. 235' - 255' - - - - 7 grams e grams. As may be seen from the figures the temperature was not very critical. however. there appeared to be a slight de- crease in the yield at the higher and at the lower tempera- tures. It was difficult to explain this. Possibly at the lower tesperature broninaticn proceeds more slowly and was not given time to reach completion. At the higher tempera- ture. possibly the tendency of the bromine to vaporise and pass off without reacting is greater than the increased tendency toward reaction. These are admitted to he not very satisfactory explanations. At any rate. since it was indi- cated that the tenperature for brcninati on was not extremely critical. and since the temperature usually taken by the bronination mixture seemed to give maximum yields of the desired product. no change was made. concerning this part of the prooeedure. Only one other slight change was made. This was made. however. for the purpose of saving materials rather than for increasing the yield. It was found that if. after the first steam distillation. the open flask containing the reaction mixture was heated for a while on the oil bath and thenixture evaporated nearly to dryness. less sulfuric acid was required to take the mixture 80% acid. the right concentration for hydrolysis of the sulfonic acid. the nut ' step in the proceedurc. successive runs of the proceedure were then made. incorporating all of the various modifications and using half nolar quantities. (double the amounts previously used). it is not believed necessary to record here all the figures obtained from these runs. The following tabulation is typical: 180.9194oo-o-7crans. 194' - 200° - . - can“...~ 200’ - 215° - - - - 7 grams. 215' - 235' - - - - a grass. 235° - 255' - - - 15 grams. The yield of 38 grams of o-bromophenol represuts a yield of «.45 which appears to be very satisfactory. The rather high fraction boiling at 235"- 265' is believed to be lastly 3.d-dibrossphenel. Following are the complete directions for the prepa- ration of sobronsphensl incorporation all of the modifi- cations previously Isntioned. The materials are taken on the basis of solar quantities. 35 THE MODIFIED KETHOD FOE; PREPARIHG O-BBOXOPEEXOL Ono mole. (94 grams). of phenol and three and one half moles. (350 grams). of concentrated sulfuric acid in a two liter. thresonecked flask are heated on a boiling water bath for three hours. stirring constantly with a mechanical stir- rer. At the end of this time the reaction mixture is cooled by replacing the boiling water bath with a cold water bath. The mixture is then made alkaline by adding a solution of seven moles. (230 grams). of'sodiun hydroxide dissolved in 700 cc. of water. Thisnuet be done very slowly on account of the heat evolved by neutralization of the acid. The alkaline solution is then cooled to room temperse turs and broninated by adding slowly one male. (160 bran). sf bromine. still stirring constantly. During this operation the temperature of the reaction nixture is allowed to rise to dO.-60.. Stirring is continued for about half an hour after all the bromine has been added. The mixture should still be alkaline. ' The reaction mixture is then transferred to a three liter flask not for steam distillation. During the steel distillation the reaction mixture is heated on an oil bath to about 150°. This removes any tribronophenol which should not appear as more than a trace. As soon as no sore tribromophenol is noticed in the dis. tillate. the steam distillation is stopped and the reaction nixture. still on the oil bath is evaporated to a thick pasty gray me. This is allowed to cool and then acidified with about oeo cc. of concentrated sulfuric acid. This mat 36 be done slowly on account of the rapid evolution of hydro- gen bromide. I The mixture in again steam distilled. this time from an oil bath heated to 2000-2100. The sulfonie acid is M0 drolyssd by this prooeedure and the brominated phenols distill over as a heavy colorless or pale yellow oil. When no more oil appears in the distillate. steam distillation is stopped. The broninated phenols are then extracted with ethyl ether. the ether evaporated off and the residue distilled under ordinary pressure. The fraction boiling fro: 194. to 200° represents practically pure c-broue- phenol. The yield should be 70-75 grams. O-bronophenol is a colorless oil with a very characteristic odor. It is rather unstable and decomposes on standing. beeoning a brown or red liquid. 87 m ESTHOD OF E. ELSE. The preparation of e-brcnophenol according to the neth of 3. Kent was carried out for the purpose of for-- in a suitable basis of comparison of the method Just de- scribed. This Isthod was referred to in the historical part of this paper and consists of the direct brosination of phenol at high temerature. Reaction. 0..“ 0—H r“? .1. HB/r ‘i 8&1 The reaction was carried out in a one liter three necked flask fitted with a nechanical stirrer. reflux condenser. and a glass tube ct rather large bore for introducing the bro-inc more. One nole of phenol. (9d arena). was placed in the flask and heated on an .11 bath to rev-180°. One nole of bronins. (ieo pass). were placed in a small flash connected with the glass tube from the reaction flask. The ' bro-ins was vaporized by warning on a water bath. the we passing over and bubbling up through the heated phenol. hiring this operation the sirture was stirred vigorously. Mom bro-ids was liberated as broniaation proceeded and passed out through the reflux condenur. the preparation being carried out in the heed..8tirring was continued for half an hour after all the bromine had been introduced. The bro-insted phenol was then cooled. washed with 80% sodiu- ”druids solution. with water and than distilled. The following is s tabulation of the results of this distillation. m‘oiov- m°-2oo° - occ‘-ou°- worse“- 235° . 255° - -l5¢rase. odlcrsee. cup-ens. «Macrame. «vane-e. i'be yield at o-bronophenol. a grass boiling st 194'- 200. rspreoented s yield of 23.2}. Aoeording to the litera- ture the yieldehould here been such use». This -thod or preparation involves one difficulty which lakes it undesirable without special equipmt. The hot hydrogen bronide liberated in the reaction attscked sort and rubber connections se rigorously that it was in- poesible to keep the system from leaking. Ibis else resulted in the {creation of a considerable amount of tar. TEE E51303 0F TAKAGI 3.33 max. this nethod was also run for comparison with the pre- viously described seth and also to check the theory of blocking with sulfonic acid groups. this has already been referred to a number of tines. According to the report of this nethoda'aoo grams of melted phenol is pieced in e five liter flash. 3800 grass of sulfuric ecid is added end heated at oo’aoo" for three hours. the disulfonic «no derivative is formed. The mixture is cooled to roe. temeraturs. diluted with 750 cc. of water. and the theoretical amount of brains added. stirring. the brominotsd phenol is obtained by stee- distillation. extraction of the distillate. then distillotios of the final product'. this method was carried out in duplicate using on half hole of phenol. (47 grass). to the‘phenol was added 17. grams of sulfuris acid and the nixture heated on a bail- ing water bath for three hours. stirring. It is interestiu that the nethod up to this point is practically identical with that found previously to be host effective. This is assumed to result in the formation of phenoldisslfenie acid. The nirture was then cooled and one half sole. (.0 grass). of bronine added slowly. When bro-inticn was ecl- plets. the nixtore was stee- distilled. The follcwiu re- sults were obtained: #1. £2. lao'-lOd’----lsgrews20grane. l“°-200'-~~-l?gross15grcls. 200°o215'----dgrens stress. 40 215'.235.----23ans across. 235' - 255‘ - - - - 11 green 11 grains. a rather large residue was left in each case. These were rather poor yields of e-bronophenel. The highest. (11 crews). was calculated to be only 19.7} of the theoretical. Besides indicating the superiority of the previously described nethod for preparing o-brcnophesol. these results had as ilpcrtent significance. the beliefs of Bette and .Bhounik of the replace-ant of the snlfosie acid group by abalegeswas strengtheudwhile the eediu sulfeeate grew was indicated to be a were effective blocking agent then the sulfcnic acid group. ‘1 THE BEEZYLAIIOI 0F O-BEOHOPEEHOL. The second part of the problem was the condensation of e-bronaphenol with benzyl chloride according to the lethod of Clnieen. This method has already been briefly referred to and in given in detail in Annolen der Chenie M2. 224. The first Claisen reaction run was on half molar basis and was carried out in the following eey. 500 cc. of tol- nene were placed in a .33.. liter three necked flask fitted with a mercury sealed mechanical stirrer and a reflux eon. denser. To this was then added one half mole. (13.6 grams) .1 of clean sodim. The flask was then heeted on an oil both until the sodium melted. stirred vigorously and allowed to cool. 01: cooling. the scan: solidified in very fine gle- bules which presented pent reacting snrface. While the reaction lunar. was still at about vo°-ao°. one half hole. 66 grail; of cabronophencleee slowly added. this resulted in the formation of the sodium phenolate: I-” O‘N‘ B:N. — —> a; (H) Ihen the o-bronophenol had all been added the Iixture wee hosted to inf-150' and allowed to reflux for about tee hours. As the reaction proceeded. the dark colored sodiu- disappeared and the sodinn phenolete appeared as a thick. 'hite. pasty less. After the c-bromophenol had been completely converted ‘2 'to the corresponding phenolate. the mixture was again al- lowed to cool somewhat and one half tools. (63 grams). of benryl chloride was added. The mixture was again heated and allowed to reflux at 150.455. for eight hours. It was then let stand over night. During this time it was assumed that the ordinary Claisen reaction took place as previously discussed. the bcnayl group substituting on the ring to for: 2-brone.6-benryl phenols 04! e~ g. and on the oxygen of the phenol to fern achrcmphenyl-ben— syl other: rt .- a (in On the following day the reaction mixture was placed in a separatcry funnel and washed thoroughly to remove the se- diuu chloride that had been formed during the reaction. It was then transferred to a distilling flask and the toluene distilled off. The residue was heated to 125' to remove all traces of toluene. The residue was then treated with an excess. (300 cc.). sf Claiscn's alcoholic potash solution. This converted the phenolic substances present to alkali salts which were in- soluble in petrolie ether. which was then used to extract the bensyl ether. The nirture was extracted three tines with 200 cc. portions of petrolic ether. ‘3 The rcsidue from this extraction. containing the al- tsli salts of’the phenolic sUbstanoes.'was acidified with not. cooling. which liberated the phenols. These were then extracted three tines. using 200 so. portions of ethyl other. the petroleum ether extract. which was suspected to contain the substituted phenylbenayl ether. was transferred to a Claieen flask and the petrclsnn ether evaporated off. All traces of petroleun other and water were removed by heating up to 125' under it me. pressure. The residue was then distilled at 2 3. pressure. yielding the following fractions: up to 155' . — - . a crane. 135' - leo'o - . - a crane. 1m'ouv----m.um. 145 else ecu-tgrans. 150° . 155 - - - - 2 grams. 1:55° . zoo - - . . 2 grams. since it was believed that the large fractions between uo‘ and 150° represented the desired product. these twe fractions were combined and rsfractionated at 2 3. pressure with the following results: Upto ld0.---- Serums. lio'oltz.----dgrnns. 142' . 144' - - - - 21 grams. 1‘4' . 146' - - - - 2 grams. 145' - 160° - - - - 2 grams. 44 The fraction boiling at mean“ was assumed to be- the hmmphenyl~benryl other. Analysis for halogen content. (page 5:5). mfimd this. The ethyl ether extract. which was suspected to con- tain the 2-brono.6-bensyl phenol. was then transferred to a Claisen flask and the other evaporated off. As before. all the other and water were removed by heating to 125’ at 15 -. pressure. The residue was then distilled at 2 an. pressure with the following results: ' Upto 1350---- Saran. 1:5'-150’---- Bar-am. 150°~155°-~~-1ogrm. 155°~1cs°~~~~ Spams. 165°-200°---- Spam. m m;- fraction boiling at root-155° acute to in- dicate the desired product and was therefore refraotieuted with the following results: Uptc ldo°---- age-ans. lbO'clbh'ov-oltgrans. 158.-» --«--lgran. no fraction boiling at iso'-1oo° was seemed to be the 2-breus.d-bensyl phenol. This was also oonfirwed by analysis for halogen content. (page 5:5). The yields in the above reaction were calculated to be 18.95 ef the ether and 10.63 of the phenol. rwe nore claissn eondensations were run using the ease i5 prooeednre'withwmeler quantities of the reagents. This was for the purpose of obtaining enough of the phenol for enslysie end.the preparation of dcrivntivee. Befroctionntion. as described in connection with.the first run. gave. for these two'moler rune. the following results: ' achromnphenylobenzyl other. 2 an. #1. $2. up to leo' . . - . 3 grams 4 grams. ieo' . 142° . - - - 8 grams 8 grams. 142° a 144° - - - - 40 grams 38 arena. 14" - 145° - - - - 2 grane 2 grams. 146° - up - - ~ - 2 grams 2 grame. Scum.6-hensyl phenol. 2 m. Upto 150°---- harm agrees. 150‘-153‘----35m33¢rm. 153‘ - up - - - - a green 5 grams. ' The yields of the ether in these tee runs were. re- spectively. 15.25: and 1‘45. The yields of the phenol were 13t3% snd.lz.5%. In order to further identify the compound sesamed to he 2-bromcphenyléhensyl ether. e Cleieen condensation was run in methyl alcohol..Ls'wes pointed out in the previous discussion. the condensation eerried out in s dissociating .nediml such to methyl alcohol. yields only the oxygen elkyleted seasoned. One fourth.nolnr quantities of reagents ‘6 'were need. The first part of the yroceednre'eae identical ‘with.thnt used in the previous rune..After the reaction mixture had.heen heated and.the reaction had gone to come pletion. the alcohol was evaporated off. water added to dissolve the salt that hed been formed in the process. and the 26hronophenyldhenzyl ether was extracted three times with 100 so. portions of petroleum ether. It was not neces- sary to one Cleicen's alcoholic poteeh in thie cone since this prooeednro does not yield hensylnted phenols. The petroleun.ether armrest was then transferred.ts e Cleieee fleet. the petrolene.ether evaporated eff. end traces of the solvent end water removed as before hyihesting to l25° st 1: In. pressure. The residue wee then distilled et 2 h. pressure giving the following fractions: h up to 135° 2 grams. 155° - 140° — - - - 2 graze. 140° . 145° - -»- - 11 grams. 145° . 150° - e - . 8 grams. 150° . 155° - - - - 2 arena. 165. . 200° - - - . 3 grams. As before. the frsctiene boiling st 1.0“.1eo° were combined and refrectioneted et 2 Elk pressure with the following reeults: Up to 140' - - - - 2 grams. 140' - 112° - - - - 1 gram . 142'“- 14e° - - - - 13 grnme. O7 1«’-146'---- lgrele. “6.-., 0......0 The large fraction ie enin assumed to repreeent the 2-hronophenyl-benxyl ether. Its boiling point. 142°-1«‘ u 2 In. preeeure cheeke with that as found from the ether eondeneetione. This in believed to definitely establieh the identity of the eoupeund in qneetion ee 2-bronophenyl- hensyl ether. 94 VARIOUS BERNATIVES OP a-aaonow-mm PHEHOLo The purpoee or thie port of the prohlee wee not only to prepore verious new emonnde bet to lee thee ee e fur- ther neene of identifying the 2-broeo.6~heney1 phenol. The first derivetive prepsred wee Roe-dihreeood-beeeyl phenol. This wee done by the direct hroninetion of the honeyleted phenol eooording to the following equations 0”!" , 044 5., é- “1 i. H H X f 7 '1' 9":- '1' H3” A eoneiderehle meat of this derivetive wee node in order that 1: night he need in the preparation or other derivatives. 13.1 crane. (.05 melee) . of adorned-beers]. phenol wee dissolved in chloroform end to it wee edddd 8.8 troll. (.05 I010. plue e 10% exoeee). or bromine else dieeelved ie ehlerotorn. The reeotion mixture wee cooled with iee. When bruinetien wee ooeplete. evidenced by the dieeppeerenee e! the hroeine color. the ehlererore wee evaporeted oft. leevb in: e white solid. This compound. efter being reeryetel- lined from petroleu- ether five tines. geve e oonetent Islting point of 90.8.. identieel with the neltinc point ee deterlined for Zoe-dihroeooe-henxyl phenol by I. H. infield. (Hester'e thesie. 1930). Thus. the identity of thie end the moumbeneyl phenol tre- whioh it wee prepared were ee- teblished. mt were propered the bensoyl end toluenesnltenyl esters of the none and dihronoheneyl phenols. Thie wee done C0 by the nothod described by Porter. Stewart end Breneh. The phenol was dissolved itfinidino end to it wee edded e 10% exceee of the ecyl chloride. After stending ever night on equel vole-o of water wee edded to this reaction mixture to tenet with the excess ecyl chloride. The lixtnre wee then eeidified with eulfnrie eoid to fern e weter eolnble eelt of the pyridine end the ester wee outreotod with ethyl ether. Iveporetion of the other eolution then cove the free ester. The first ester prepared wee the boneoyl ester of Daehronooeebens’) phenol. 8 create of the phenol were die- ' solved in 20 none of pyridine end to this wee edded “0 train. (e oeleuleted 10$ excess). of bound chloride. the proceednro wee followed es described end the ester for-ed eecording to the equetion: 0°.C d-c: O ‘EQ O .9 .C Evnporotion of the other extreet geve e white solid which efter being reoryetellined fron ethyl alcohol five tines. ehowed e ecnetent Ieltin; point of 39. 5‘40“. rho p-tolneneenlfonyl ester“ of 2-bronooooboneyl phenol nepreperedintheeeleweyfre-Bgrelsof thephenolend 6.0 areas of rtelnonoenlfonyl chloride. eosording to the (/0 [Ff/Q . lei/V Rceryetellieetion of this compound five times fro. ethyl slcohol save e white crystelline compound having e oonotent melting point of 85. ”80.0 . The bennoyl ester of 2.4-dihrcnc.d-beneyl phenol wee properod in the sons wey using o trees of the phenol end 2 mile hensoyl chloride. ecoording to the following oqnetion: °\ 3-11-31 I I rive rooryetellieetions of this compound frcn ethyl elcohol cevo e white Wine compound with e constent nolting point of 102'. The p-toluenesnlfonyl ester of 2.4-dibronoydvboneyl phenol wee properod free 4 stone of the phenol and 2.9 (rem of p-tolnenosnlfonyl chloride. 0 .. a I“ at” ,\Q " o 5 ~ 0 Q 3 / z \ "’1‘ /’\ :1 Br ‘ ‘< \, t ' 1%de on) This compound. when purified by euooeoeive reoryetel- lisetions from eloohol geve e white crystelline compound hnvina e constant melting point of 119°. The nethyl and ethyl others of 2-hrmo.6-beneyl phenol were next proper-ed in the following wey: The phenol was dis- eolvod in the corresponding elcohol end the theoretical encunt of sodiun edded to fern the eodiun phenoleto. When 61 this reeoticn was complete the theoretical enount of the elkyl iodide wee edded. the nixtnre refluxed for five hours end ellowed to etend overnight. The eloohol wee then eve- poreted off end the residue weehed with weter to remove the sodium iodide forned in the reaction. The other nee «- treoted with ethyl other end wee obteined by oveporetiu off the solvent. By this method the nethyl other one prepared. using 20 trons of 2-brcno.d-benryl phenol. 1.75 grens of codinn. 10.8 arm of methyl iodide end 25 cc. of methyl eloohol. The reectione ere represented by the following equations: ‘ Vii ' 0 INA this other wee then purified by frsotionel distilletien et reduced pressure. It wee found to boil et 139'-1o1' et 2 III. pressure. The ethyl ether wee prepered in the some wey. using 20 grams of the 2-brm.d-bensyl phenol. 1.75 grams of Iodine. 11.5 none of ethyl iodide end 25 so. of ethyl eleohol. The following reecticns were involved: 52 Thie other me also purified by fractional dietilletion at reduced preeeure. n was found to boil at u1'-ua' u 2 m. pressure. AMISIS 01' mm VARIOUS PBEPARAIIOHS. The final port of thie problee ooneieted of the enelyeie of eeoh of the verione oupounde prepared free ochre-epheml for the purpeee of deter-min; their eenetitution end thee verifying their identity. The enolyeie wee node for helegen eentent. We no done by the Perr Bolt method ee deeeribed by J. Leap end H. Brodereoe. (I. leer. Chen. soe. 39. 2069. lOl'I). implicate eelplee were run on ell but two ef the eonpounde. the benreyl end telneeeeulfenyl eetere of 8.4-dibrono.6-beneyl phenol. There one only e .ll elont of theee tve compounde on bend end einee in eeeh eeee the firet enelyeie cove reeulte that oheeked very eetiefeev therily vith the theoretioel veluee. it wee not ooneidered neeeeeery to run duplieetee. Jello-inc ie e teboletiee of the reeulte of the verioue enelyeeee 2-bronophenyl benxyl other. 'vt. of eample wt. of bromine Z of bromine f of bro-lee determined by enolyeie oelenleted #1. .2021 .0603: 30.115 3.33% #2. .2110 .06381 30.24% 2-brono . 6-benryl phenol . vt. of sample wt of bromine :1 of bromine % of bromine determined by enelyeie onlouleted 51. .2013 .06079 30.20% 30.381 #2. .1952 .05934 30.26% 2.4-dibreuo.6-beney1 phenol. wt. of eemple wt of bromine :5 of bromine '5 of bromine determined by enolyeie calculated #1. .2082 .0968? on. 8% £6.75; #2. .e131 .0995: 45.52% Beneoyl eeter of 2-broeo.6-benry1 phenol no *Q 0/ .1 ‘V <3 , :4 wt. e1 couple wt. of bromine 1 ef bromine 1 of breeine (3.. deter-ined by enolyeie celeuleted #1. .1986 .04169 214% 21. 77$ #2. .2011 .ouo: ‘ 91.57: potelneneeulfenyl eeter of 2-brono.6-beney1 phenol “$70 ‘9‘) . fig wt. of emple wt. of bromine % of bromine 3 of bromine detereined by enelyeie eeleeleted #1. .2092 .03991 19.09% 18.16} #2. .2085 .03988 19.18% -—:.". O Benzoyl ester of 2.4-dibrom.6-beneyl phenol. o/‘EC C wt. of eelple wt. of bromine 1 of bromine W of bromine determined by enelyeie ficelculotcd I1. .2013 .07279 35.64% 35.84; 55 0\:C° 0c wt. of m1. wt. of bromine 5'.’ of bromineW Wof bromine by ennlyeie calcnleted p-telueneeulfonyl eeter of 2.4-dibrcno.6-benry1 phencl\ Qh‘ determined #1. .2042 .06556 32.11% 52.22% Methyl ether of 2-brm.6~bcnryl phenol. t3“ ...<\ wt. of couple wt. of bromine 1 of bromine 5‘ of brcnine determined by enalyeie celcnleted #1. .1951 .05541 28.40% ‘ 28. 85% #2. .2013 .05729 28.d6 Ethyl other of 2-brone.6-benzy1 phenol. wt. of angle wt of bromine 5 of bromine % of bromine determined by analyeie oelculntcd #1. .1903 .0519? 27. 31% 27.06% #2. .1997 .05448 27.28% In eech eeee. the etrncture thet had been eeeigned to the compound. wee verified by enelyeie. The reeulte of the work outlined in thie theuie to: be mixed in the following me A eatieraetory nothod was developed for the preparation of o-bromophenol. By oouparinon with other simple methods of preparation thie method woe ohm to be euperior. The 716?. or Betta and Shoumik. that the eultonie eoid group may be readily replaced by halogens. wee eupported. The eodimn ultono 7‘13. ehown to be euiteble for blocking the substitution of halogen. rue oxygen and carbon benzylati on products or o-bromophenol were prepared and identified in warloue we. The following new compounds were prepared: The bemyl eeter of 2-bromo. Gcbeneyl phenol. The p-toluene eultenyl eeter of 2-bromo.6-beneyl phenol. The beneoyl eeter or 2.6-dibronofi-beney1 phenol. The p-tolueneeultonyl eater ei’ 2.4-dibrono.6-beneyl phenol. The nothyl other e: 2-brone.6-beneyl phenol. The ethyl ether or 2-brofio.6—beneyl phenol. z.t-dibrono.6-beneyl phenol wee previouel: prepared and identified by 3'. H. Mold. 2-bronophewl-benzyl ether and 2.brono.6—beneyl phenol were prepared by R. Downer but were .not identified by enelyeie at that time. A 4_—_—..—.__-‘ -AA. ‘emg v A 5'! W 03‘ REACTIOHS. 9-!" -fl 50,0" 3;”!- new!“ 1",“, ———) “no" -—-’ 1e.‘——-) “10” 3’0" 0-“ N - 15' «0 Our 3,!” Cr 60;.” Dz. 09'“ (may: annual) (1.1....) 1/1, 9 u . u -« C3 °' an Hf-H'IA 1.... E- N «a. ’7 9 5' macaw“; "‘ ' ° 4"“,Cfl ‘W “a“? :\ N H .1 ”-3-” H-é‘" O O u é-N H E" .= 9 are o ' O O u 00 0:0 fio o «.0230 .8259 efigo Bmwt —|13‘/3.m“ “Inf-HIV!“ .151“? M31!“ 4" HP, "9' . . M P. “a. ‘4 m1 R “ W Il‘ M ||I Ill 'TITI‘ITMI WilUllllHlllllHt 6043 mlflwuosoe 3