0 I\) .‘l I“ II I I‘ lI‘ II‘ [‘III I'!‘ I I I I II I I‘l III I l I I I II ‘i'l III II II III I ‘I I (00101 REACTION OF ORTHO’ CHLOROPHENOL AND {DRTHO~ BROMOPHENOL WITH TERTIARY AM‘YI. AND TERTIARY BUTYL ALC’CHOLS IN THE PRESENCE OF ANHYDROUS ALUMINUM CHLORIDE Thesis for the Degree of MI 5.. MICHIGAN STATE COLLEGE Aubrey A. Larsen I944 ___'-_—-o- ._ _.____,. swash: ' -.'" ""CS‘\.'.::.'¢ 1 . .v '. ‘1 ..'.y .- ,". K' J (,3 .4; , fa (KW-'FPV"M'V N‘. ".5‘ m " “ '4: '5‘" "‘V.‘) 5’ ":v_.““/‘- M M..— ..,,. A I . . .I "'3‘! | y I I . .r .~ I‘lna prl .I.. I . I L. n . .L .. . t. .. o u... I . . . .aI . . .. REACTION OF ORTHO~CHLOROPHENOL AND ORTHO-BROEOPHENOL WITH TERTIARY AMYL AND TERTIARY'BUTYL ALCOHOLS IN THE PRESENCE OF ANHYDROUS ALUMINUM CHLORIDE by AUBREY A. LARSEN A THESIS submitted to the Graduate School of Michigan State College of Agriculture and Applied Science in partial fulfilment of the requirements for the degree or EASTER OF SCIENCE Department of Chemistry 1944 ACKNO FL ED011352} The writer wishes to express his appreciation for the guidance and helpful counsel given hin.in this work by Dr. R. C. Huston. (bf OHM. -' ()1gi.’ .’ _1_ :J I. II. III. IV. V. VI. rpm". .ITTN'“! *I. L‘lJODLI'VLIOiI 00000.eeeoeooeeeeeeeoeeeeeeeeeeeeee EZIhSrFORICJ.}L COOCOOOOOOOOOOOOOOOOOOOOOOO-OOOOOIOOOO C‘W‘pa" ..\. v (-4.?"15 Jiji-i.)til"(Il .SltitiL 0....0.00.00.00.00...eon-0.0.0.000. A. :zaterials OOOOOOOOCOOOOOOIQOO0.000.000... B. Condensation of Tertiary Butyl Alcohol Eith Ortho-chlorophenol ................. C. Condensation of Tertiary Amyl Alcohol With orthO’CthrothHOI ooeeeeeeeceeeeeeo D. Condensation of Tertiary Butyl and Ter- tiary Amyl Alcohols dith Pararchloro- phen01 .................................. E. Condensation of Tertiary Butyl and Ter- tiary Anyl Alcohols with Ortho—bromo- phen01 eeeeeeeooeeoeeeeeeeoeecoco-coco... l. ?reliminary Investigations ....... 2. Condensation of Tertiary butyl Alcohol with Ortho- bromophenOI oeoeeeeoeeooeeeeoeeooo 3. Condensation of Tertiary Amyl_ Alcohol Eith Ortho- bromophen01 oooeeeooeeeeeoeoeeeeoe F. Acetylation of ?henols .................. G. Derivatives 0.0.0.000...OOOOOOOOOOOOOOOOO DISCIISSIOTJ 0.0...OODIOOOOCOOOOOOOOOO00.0.0000... ‘ RY QquuA. Doeeeeoooooceoeeoeeeecoco-0.00.09.00.00. BIBLIOGRE:L.-JEIY COOOOOOOOOOOCOOOOOOIOOCOOOOOOOOOOOC 1‘) £00 12 16 17 18 '18 20 IKTRODUCTION The condensation of benzene, phenol, and of other aromatic connounds with aliphatic and Fixed aliphatic-aroma- tic alcohols, using anhydrous aluminum chloride as 8 cata- lyst, has been the subject of extensive investigations in this laboratory for a number of years. In 1957, Huston and Coleman (1), investigated the reaction of ortho- and para-chlorophenols with tertiary amyl and butyl alcohols in the presence of aluminum chloride. It was found that both alcohols condensed with o-chlorophenol to yield the p-t-alkyl-o-chlorophenols. These two tertiary alcohols failed to condense with para-chloroptenol under the conditions studied. It is the purpose of this present investigation to supplerent and to extend this work. F. I 3'? Z? I. C AL 2 The action of anhydrous aluninum chloride and of other rearents on substituted aromatic compounds, either in, or not in, the oresence of other compounds has been the sub- ject of investigation since the latter part of the last cen- tury. Perrier (2) heated ortho- and para-chlorophenols with aluminum chloride in dry carbon disulfide and obtained, upon cooling and filtering, crystalline products which ana- lyzed as (06H5001)2A12014. These compounds had definite melting points. The original phenols were regenerated by the action of water. Dumreicher (3), in 1882, found that alCls reacted with bronohenzene at elevated temperatures, 1300 0., to give largely unchanged material and some benzene, dihronohenzene, and HBr. Chlorobenzene was unaffected by alClS under simi- lar conditions. lodohenzene gave a reaction similar to that of bronobcnzene, except iodine was recovered instead of RI. Leroy (4), in 1887, observed that p-dibromobcnzcne in the presence of A1013 at 100° 0., gave tribronobenzene, nonohronobenzene, and neta—dibronobenxene. Kohn and Ruller (5) debroninated tribrononhenol, with $1013 and benzene, at 1000 C. Bromobenzene and phenol were obtained, together with unchennsd tribronoohenol. Under similar conditions, trichloronhenol was unaffected. Kohn and Bum (6) obtained Peta-hrorotoluene and phenol from tribromophenol and toluene by the action of 3 A1013 at 100° C. Similarly, p-brorophenol rave reta—broro- toluene and phenol. Kohn (7), in 1931, stoned that tribronoresorcinol was also debrominated by benzene and A1015. aromatic com- pounds, such as bronochlorobenzene and bronotoluene, also gave the corresponding debromineted compounds. Selkind, Stetzan {8) and Lohfert (9) observed that when some of the dibrononapthalenes were heated for several hours in the presence of A1013, small amounts of isomeric dibromonapthslenes, along with the original bromo compounds, were recovered. Copisarow (10) observed that when bromobenzene and 51013 were heated on the ester bath for eisht hours, a mix- ture of benzene, the three dibronobenzenes, the 1,5,5 tri~ bronobenzene, and some of the 1,2,4 isomer was obtained. Para-dibromobenzene yielded benzene, brorobenzene, a mixture of dibronobenzenes,and the l,2,4~ and the l,5,5~tribronoben— genes. Chlorobenzene was not affected by £1815. Tisration of the bromine atom was increased by continuous reroval of the benrene forced, and by carrying out the reaction in a current of 301 or H2. Berry and Reid {11) alkylated bromobenzene with ethylene in the presence of $1013 and isolated benzene, ethylbenzene, diethylbensene, and brominated ethylbenzenes. Bruce and Todd (12) obtained 1,3-diis0propyl-4- bronobenzene from the reaction of bromoben one, iSOpropyl chloride, and nlCl5 at 0° C. ho debrominated products were reported. In most of these instances of bromine migration or removal, the conditions were generally more severe in time, temperature, and in the amount of A101 then usually followh 3 ed in this laboratory. However, even under these severe conditions, the chlorc isolcgues Of these bromo compounds were not dehalogenated. Suter (13) found that when p-fluorOphenetole was refluxed with benzene and 31013, the eXpected p—fluorcphencl was obtained, plus some other phenolic product. ' weston and outer (14) later showed that this phenolic product was para- hydroxybiphenyl. Paraehydroxybiphenyl was then obtained di- rectly by the reaction of benzene and A1013 with p-fluorc- phenol. Para-chlorOphencl did not show a similar reaction with benzene and A1615. Henna (15) states that A1013 replaces fluorine readily in aliphatic or aromatic compounds. In 1939, ficrris and Turner (16), investigated the reaction of the three isomeric chlorotcluenes with A1013 and HCl, under mild conditions. They observed both disproporv tionaticn and rearrangement as a result or migration by the methyl group. There is considerable reference in the literature to the dealkylation or alkylaromatics by A1013 and other acid catalysts. It has been shown, however, that £3101:5 will remove all types of alkyl groups from an aromatic nucleus. On the other hand, Ipatiefr and Corson (17) found that 5 ferric chloride, sulfuric acid, and phosphoric acid remove only tertiary alkyl groups readily from an aromatic nucleus. Crlov and Vaisfeld (18) studied the dealkylation of xylenes and found that moist $1313 was very effective for dealkylation, $101306H20 being the most effective. Nightingale (19) gives an extensive review or both alkylation and dealkylation of benzene in the presence of A1013. filtration is, in many resoects, analOgous to al- kylation. There are innumerable references in the litera- ture where debromination was observed when bromoaromatics were nitrated. (In 1896, Jackson and Dunlap (20) obtained uni- dentified debroninated products from 2,4,6-tribronoresorcin- 01 by the action of boiling water. Baichikov and Zadbrodkin (21) obtained picric acid and bromine by the action of a nitric-sulfuric acid mixture on symmetrical tribronophenol. Without the sulfuric acid, the amount of debromination was small. Raiford and Heyl (22, 25) found that both tribromo and triiodophenol had either an ortho or a para halogen re- placed by e nitro group when these phenols were treated with sodium nitrite and acetic acid. Trichlorophenol was unaf- fected under the sane conditions. Raiford and leRosen (24) nitrated brominated fluorophenols by acetic acid and sodium nitrite. Shea 2,4,6- tribromo~3~fluor0phenol was nitrated, a bromine atom was 6 replaced by a nitro group in either the "2" or the "4" posi- tion. hhen 2-f1uoro-4,o-dibronOphenol was nitrated, the products were 2-fluoro-4-brono-6-nitrephenol and 2-fluoro-4- nitro-G-bronOphonol. The product from 2,6-dibromo-4-fluoro- phenol was 2-bromo-4-fluoro—6-nitrephenol. Similarly, Raiford and fiiller (25) studied chloro- broncphenols under like conditions and in all cases, it was the bromine that was replaced by the nitro group. Emerson, Bart, and Deutschmann (26) observed a de- bromination of tribromoaniline when refluxed with zinc, HCl, acetic acid, and formaldehyde. The resultant product was dimethyl-p-bronOphenylanine. Hodzson and Kixon (27) subjected 4-chloro—3-nitro- aniline to diazotisation with haficz and either HCl or H2304. Depending upon the acidity of the solution, the product was a 4-chloro~2~nitrobenzenediazonium.salt or 2-nitrobenzene-4- diazo oxide-l. In the case of 4-fluoro-3anitroaniline, the product was exclusively 2-nitrobenzene-4-diazo oxide-l. In this laboratory, brass and chloro compounds have been reacted in the' presence of minimum.amounts of 31013 at room temperature without any observed dehalogena- tion. Huston and Warren (28) benzylated o-chlorOphenol in the presence of £1015 to obtain both d-benzy1~2-chloro— phenol and 6-benzyl-2-chlorcphenol. Huston and Guile (29) reacted meta-chlorobenzy1~ chloride and 2,6-dichlor0phenol in the presence of AlCl3 to obtain 4-hydroxy-3-5-3'-trichlorodiphenylmethane. Para-broaobenzylchloride was reacted with both phenol and 2,6-dibrom0phonol by Euston and D'arcy- (30) to give 4-hydrozyb4'-bronodiphenylmethane and 4-hydroxyb3,5,4'- tribromodiphenylmethane. Huston and Fayerweether (31) successfully obtained 4-hydroxbe'-bromodiphenylmethane and 2-hydroxy~2'-bromodi- phenylmethane from ortho-bromobenrylchloride and phenol in the presence of A1013. Huston and Neely (32) benzyleted 2,5-dibrom0phenol with meta-bromobenzylchloride to yield 4-hydrozy~3,5,S'-tri- bromophenylmethane. Huston and strickler (33) reported the condensa- tion of n-propylphenylcarbinol and 2,6-dibrom0phenol with A101 to give 4(alpha-phenylbutyl)-2,6-dibronophenol. 3 2,6-dichlorophenol was condensed with benzyl alco- hol and £1013 by Huston and Eldridfe (34) to give 4-hydroxyb 3,5-dichlorodiphenylmothane and the corresponding ether. In 1937, Huston and Coleman (1), investigated the reaction of ortho- and para-chlorophenols with tertiary amyl and tertiary butyl alcohols in the presence of anl:5 at room temperature. Tertiary butyl and tertiary amyl alcohols both condensed with o-chlorOphenol to give the para-t-elkyl or- tho-chlorOphenols. Both of the alcohols failed to condense with para-chlorOphenol under the conditions studied. Klarmann, Shternov, and Gates (35), in 1953, 8 prepared para-t-ai"‘-ortho~clloroohunol without reporting the netted of prep ration. Fara-t-butyl-o—chlarophenol ..as prepared by 21113 (ed) by the chlorination of» mt-butyl-phenol. Jieilsrly, Llarmann, Gates, shtornov, and Cox (3 7) brosinated p-t-asyl phenol to give p~t~asyl~o~bronophenol. Kills (36), by the same procedure, obtained a sinilnr pro- ‘ duct. In 1395, Dains and Rothrock (38), prepared p-t- buty l-o-brorOpt .enol by hrorinetinc, in carbon disulfidc, the sodium as t of p-t-butylphcnol. After distillation, a dark oil v.°as left ".hich was hoe t pur ficd by steam distillation. rho oil then solidified and was identified as p-t-butyl-o- bro: Opt enol. Huston and Agett (45) bromin ted p-t-butylphenol (A >u he obtained p-t- cu,yl-3-'ro'or‘cnol. fhe reaction of para- bronophnnol with tertiary butyl alcohol in the presence of nlCls was also intestigated. Lo elhylated product was ob~ tained, 7d: of the original phenol he in: recovered. In the reaction or the tertiary b1t”l alcohol wit h n-broronhonol in the presence of phosphoric acid, 95? of the orioin l phenol WUB I‘CCG‘VG‘I'Cx o EXPERI-L¢£I‘I'PAL 9 A. Materials 1. Ortho-bromOphenol The nethod of Huston and Keeley (39) was used to prepare o-bronophenol. Three moles 282 grams) of U.S.P. phenol and eight moles (820 grams) of concentrated sulfuric acid (density, 1.84) were placed in a five liter, three neck flask, and were heated at ICC-110° 0., with stirring, for two to three hours. After the solution had cooled, 700 grams of freshly distilled nitrobenzene were added. The solution was cooled with an ice and salt bath, and 150 grams of melted, fuming sulfuric acid (403) were added, with stirring, and at such a rate that the temperature of the solution did not exceed 10° C. After bringing the solution to room temperature, 300 areas (5.8 moles), of bromine in 500 areas of freshly dis- tilled nitrobenzene were added, with stirring, over the course of three to four hours. Stirring was continued for three to six hours after all the bromine had been added. Then, sufficient NaHSO was added to reduce the excess bro- 3 nine. Enough water was added to fill the flask and the two layer system was stirred for a short tire to extract the sulfonated phenols. The water layer was then separated from the nitro- benzene layer. The water layer was then subjected to dis- tillation. shen the temperature of the water solution reach- ed 115-1250 0., the characteristic odor of o~bromophenol was lO noticeable in the distillate. at this point, the oil bath temaernture was raised to 200° 8., and suoerheated steam (230° 0.), was nasscd into the flask. The o-broaonhenol steam distilled rapidly as the sunerheated steam hydrolysed t’ he sulfonic acid grouse. The two layer distillate was extracted with ethyl ether and the resulting ether layer dried over anhydrous Ha2304, in the cold. The ether was boiled off and the phenol residue was subjected to vacuum distillation. The o-bromonhenol was distilled tsicc at reduced nreosure tarsush a so cm. glass- packed, heated column. The resulting o-hrorophenol boiled at 76-770 0., at ll mm.,, and yields of 30-35} were consis- tently obtained. analysis: Calculated for CGHSUBr. Br, 46.2. Found: Br, 45.9 - 46.4. infractive index, ago a 1.5747. 2. Crtho—chloronhcnol gastron’s shite label o-chlcrophencl was used. as with o-bronoohenol, the material hecxse colored upon stand- ing if it was not sure. The o-chloroohenol was distilled at least twice before :sinr, through a 45 cm. modified Claisen flask, and has a boiling point of 36-870 C. at 13 mm. 3. fara-chlorophcnol Ihc p~chlororhenol obtained, an oily solid, was best purified by distillation. The purified phenol bailed at 33-890 C. at 3 nm., throuch a 45 cm. rodifiad Olsisen flask. 11 4. Tertiary Butyl and Tertiary Amyl Alcohols Both of these alcohols form constant boiling mix- tures with water. Young and Fortey (40) found that tertiary butyl alcohol forms a mixture which boils at 79.90 C. at 760 mm. and contains 21.7% water. Sirilarly, Ayres (41) showed that tertiary amyl alcohol forms a nixture which boils at 87.20 C. and contains 22$ water. Both alcohols were distilled several times, the foreruns being discarded. To insure complete removal of all water, the twice distilled alcohols were again distilled over sodium, the amount of sodium.hein3 1/50 of the weight of the alcohol being distilled. In this manner, t-butyl al- cohol, boiling at 80-810 C. at 744 nm., and t—amyl alcohol, boiling at 99-100.5° C. at 737 mm., were obtained. 5. Petroleum Ether The petroleum.ether was tested for unsaturated compounds before use and was then dried over sodium. 6. aluminum Chloride Baker's analyzed, anhydrous, sublimed AlCls' was used. No difference was observed in the over-all catalytic action between the granular and the pea size lels. 7. acetic Anhydride Eastman's yellow label (practical) acetic anhy- dride was distilled and the fraction boiling from 135-157° C. at 743 mm. was used. B. Condensation of Tertiary Butyl Alcohol 12 '““ filth UrtHo-éhlorophen61 A 500 ml. three neck flask was fitted with a mer- cury seal stirrer, a condenser, and a thermometer. To the flask was added & mole (32 grams) of o—chlorophenol, t mole (18.5 grams) of t-butyl alcohol, and 150 ml. of anhydrous petroleum ether. The flask and contents were cooled to 0-100 0., the cooling was then removed, and the anhydrous A1013 was added. In host cases the temperature was not allowed to go above 30 ° C. The rate of addition of the A1013 was used as much as possible to keep below the desired temperature. As the A1013 was added, the reaction mixture went through a series of color changes, usually ending up with an orange-red color. Ten to fifteen minutes after the first A1013 had been added, a precipitate 'other than undissolved A1013 formed or settled out in the reaction mixture. The stirring was continued for five to eight hours after all of the A1013 had been added, and the reaction mixture was then left to stand overnight. Ice, water, and concentrated HCl were added to the reaction mixture. The upper petroleum ether layer, violet in color, was separated from the water layer. The water lay- er was washed three times with ethyl ether and then the ether washings were added to the original petroleum.ether layer. The combined other layers were washed three times with water, as o—halophenols cannot be washed with Nezco3, hohlleben (42), and the color of the ether layer changed from violet to brown. Then the ether layer was placed over 13 anhydrous Na2804 in the cold to dry. After drying, the ether solution was subjected to fractional distillation. The following is a representative fractionation of the other solution from the reaction. A 60 cm. glass-packed, heated column was used. 1. up to 40° c. at 738 mm. Did not decoloriie Br . ' - Gave a positive Beilsgein test. 20 40 to 500 Co at 738 We Did nOt decOlOl‘lzo Bro. Gave a positive Beilstein test. 3. so to 55° c. at 738 mm. Decolorized Br . Discharged color of neutral 1': LI; 0 0 Gave a positive Beilstein test. Positive test with alcoholic 4. 55 to 50° c. at 738 mm. Same as $3. As the oil bath temperature was raised to 180° 0., there was little or no further distillate until the pressure was reduced. 5. up to 1000 C. at 7 mm. Very little distillate was ob- tained above 60-610 0., the boiling point of o-chloro- phenol at this pressure. 6. 100 to 1100 C. at 7 mm. Bulk of the material was pet- butyl-o-chlorophenol which boiled at 105-1080 C. 7. 0n occasions,e small amount of liquid was obtained above the range of fraction six. This amount was never more than 2 or 3 milliliters. 8. Resulting residue was black and viscous and showed no signs of crystallizing after standing for six months. Above the range of the volatile distillate, there was very 14 little material other than the unreacted o-chlorOphenol and the alkylated product. ‘ The o-chlorophenol from fraction 55 became deeply colored and had to be redistilled several times before it remained clear. The alkylated chlorophcnol did not become colored in this manner. The amount of material boiling from 50-550 3., fraction J3, was always very small. If there were any un— reacted t-butyl chloride present, it would have been found in this fraction. Tertiary butyl chloride gives a positive test for unsaturation. ho material boiling from 78-830 0., the boiling range of t-butyl alcohol, was obtained. On repeated fractionation, p-t-butyl-o-chlorOphen- 01, with a boiling point of 93~94° C. at 3mm., was obtained. The diphenylurethan derivative, recrystallized from petroleum ether, had a melting point of l40-141° 0. Coleman (1) reported the melting point of this derivative as 142~143° o. Para-t-butyl-o-chloroohenol Bio : 1.090s n30 “ 1 5309 4 ’ ' B.P.745 : 238.8—239O 0. Surface Tension: 34.2 dynes/cm. (DrOp height) Surface Tension: 35.2 dynes/cm. (Du Kuoy) Analysis. Calculated for 010H13001: 01, 19.21 Found: 01, 19.37 :ills (36) reported the density of chlorOphenol as DES 2 1.009. Of filCls Eleven condensations, was varied, 15 p-t-butyl-o- in which the molar quantity were run with t-butyl alcohol and c- chlorophenol. The results of these runs are tabulated below. 4; Run , Molari Highest Per Cent .Color of doaoral Rump euan- Reaction Yield of Reaction nemarks ber . tity Tempera- P—t-hutyl- After of ture o-chloro- Addition A1013 phenol of all A101a fl. 1 1.0 40° 0. 345 light-red ;_ 2 1.0 30° 0. 525 orgnge 3 1.0 330 C. 541% orange 4 1.0 35° C, 40% orange A101 was not 5 0.60 0 violet anhydrous 6 0.60 30° C. 47% orange 0 180,?» recovery 7 0.40 34 C. 10% orange o-chlorOphenol 92% recovery 3 0.40 31° 0. 0 violet o-chlorophenol 9 0.50 30° 0. 35% orange 89% recovery 10 0.50 27° 0. O violet o-chlorophenol 11 0.60 310 C. 50% red orange C. Condensation g; Tertiary Amyl Alcohol 16 .With Ortho—chlfirogfienol The method of condensing t-amyl alcohol with o- chlorophenol was the same as that used to condense t-hutyl alcohol with o-chlorophenol. As in the previous condensa- tions, the distillation yielded sharp fractions which were easily and cleanly seoarated. The yield of p-t-amyl-o—chloronhenol varied with the molar quantity of A1013. ‘Fifty per cent yields were ob~ tained when more than 0.6 of a molar quantity of A1013 was used. Below this amount, the yields dropped off as the amount of A1013 was decreased. ‘ Para-t~amyl-o~chlor00henol has a B.P. of 119-122.U c. at 8 mm. and 103-104° c. at 1 mm. The diphenylurethan derivative, recrystallized from petroleum ether, had an m.r. of 113.5-115° 0. Coleman (1) reported the melting point or this derivative as 116-1170 0. Para-t-amyl-o-chlorOphenol 02° : 1.0305 n20 : 1.5313 B.?.745 : 257.6-2580 0. Surface Tension: 34.7 dynes/cm. (Drop Weight) Surface Tension: 35.8 dyncs/cm. (Du Nuoy) Analysis. Calculated for CllfiquCl: 01, 17.85 Found: Cl, 17.69 D. Condensation g; Tertiary Butyl 17 And Tertiary Amy 00 013 With—Para~chlorgnhen01 These two alcohols failed to condense with para- chlorophenol in the presence of A1013, either at room temp perature or at slightly elevated temperatures, 45-600 C. The general method of carrying out these reactions was the same as that used for o-chlorOphenol and t-butyl and t—amyl. alcohols. A Skellysolve was used in the place of petroleum.ether for the higher temperature runs. The amount of A1013 was varied between 0.5 and 1.0 of a molar quantity. Recovery of at least 90% or the original phenol was observed in all cases. E. Condensation of Tertiar - 18 1nd artisr" .a 1" “3.1.0:; \ rtHO-EF:); 051.1 —L{)I l. Prelir inary Investigations In view of the results obtained from the condensa- tions of e-chlorophenol with t-hutyl and t-amyl alcohols, it was decided to carry out this part of the investigation under similar conditions. at the start of this series of condensations.the removal of bronine from aromatic compounds in the presence of £1013 was known to the writer, but its significance was not appreciated. 3 quarter of a mole of o—broaOphenol and one quar- ter of‘a mole of the alcohol were added to 150 ml. of anhy- drous petroleum ether. The solution was cooled and 0.5 x i of a mole of 11013 was slowly added, at the same time keep- ing the tenoerature or the reaction mixture below 30° C. The resulting mixture was stirred, allowed to stand, and was then worked up in the usual manner. After drying the other extracts, the other was removed and the residue was distill- ed at reduced pressure. Unreacted o-bromophenol was collected. The vapor temperature rose steadily and then a solid distillate, with both t-butyl and t-anyl alcohols, was obtained. This dis- tillate solidified in the side arm of the modified Claisen flask and in the receiver. less trouble with solidification was exocrienced when a water pump nae used for obtaining the reduced pressure. The solid material loohed like a definite crystal- line substance, tozether with a smaller amount of an oily 19 liquid._ This mixture melted over a wide temperature range. Repeated distillation effected little separation of the solid materials. -hhen synthetic mixtures of p-t- alkylphenol and p-t-alkyl-o-bromophenol twere distilled, a solid material. similar to that recovered from the A1613 condensation. was obtained. Other physical methods were then tried in order to effect a separation. Among these were steam.distillation from.an alkaline solution, recrystallization from petrOlcun ether or from benzene, extraction with NaOH (and subsequent treatment of the alkaline solution with H01 and other), and extraction with boiling water. In all of these cases. p~t- alkylphenol. in varying degrees of purity, was obtained. In ‘none of these cases,howevcr, was separation selective enough to completely separate the elkylphenol from the .other pro- duct or products in the solid distillate. Acetylation of the various phenols that might be in the solid distillate material showed that the acetates could be separated by fractional distillation, and that the original phenol could be readily regenerated fron.thc ace- tate. Similarly. phenol can be separated fron.o-hnnncphenol by this method. With this means of separation, a more thor- ough investigation of the condensation of o-hromophenol with t~amy1 and t-hutyl alcohols was undertaken. 20 2. Condensation of t-Butyl Alcohol With o-BromOphenol One half a mole {86.6 grams) or o-bromophenol and one half a mole (37 grams) of t-butyl alcohol were dissolved in 200 m1. of anhydrous petroleum ether. The solution was cooled with ice. the cooling was removed, and then 40 grams (0.6 x k mole) of 11013 were slowly added, with the temperau ture of the reaction mixture being kept below 30° C. The usual color changes were observed, acid gas was given off, and a solid material settled out or the solution about tren- ty minutes after the first A1013 had been added. The mix- ture I83 left to stir. at roon.temperature. for seven hours. The reaction mixture was worked up in the usual manner and the other layers were then placed over anhydrous Nazso4 in the cold to dry. After drying, the ether was removed and the residue was separated into three main fractions by die- tillation at reduced pressure. Fraction # I 120° C. at 13 mm.. 48.9 grams Fraction # II 120 - 124° 0. at 13 mm.. 50. grams solidified in receiver. Fraction # III 107 - 110° C. at 3 mm.. 2. grams Fraction # IV Residue. Fraction #1 was redistilled and the resulting liquid, boiling at so—ae° c. at 13 mm.. was analyzed for bromine by the Carius method. Found, Bromine, 43.4%. Theo- ry for o-bromophenol, 46.2% bromine. 0n the basis that o- bromophenol was the only bromo compound present, this distillate was 93.7% o—bromophenOl. The other material 21 present was considered, without further investigation, as phenol, according to hohlleben (42). Fraction #II was analyzed for bromine by the Parr Bomb method, and was found to contain 5% bromine. 0n the basis that the bromo compound present was p~t-butyl-o-bromo- phenol. the analysis indicated that the solid distillate ma- terial contained 14% p-t-butyl-o-bromophenol. This analysis further showed that the crude yield of the p-t-butylphenol was 52% of theory and the yield of p- t-butyl-c-bromophenol was 6% of the theoretical. With the results from.the bromine analysis. frac~ tion $11 was acetylated. The resulting acetylated material was distilled at reduced pressure. Fraction # I 110-1200 0. at 3% mad. 3.4 grams. Ni?! 1.5061 Fraction # II lac-125° c. at 3% mm..36.6 grams. n59: 1.5001 Fraction #111 l30~138° c. at 3% mm., 7.8 grams. N39: 1.5227 Part of the acetylated material from fraction #II was saponitied. The resulting crystals, after recrystalli- zation.rrom.petroleum ether, were identified as p-t-butyle phenol. p-t-Butylphenol M.P. 96~97° c. _ Analysis. Calculated for 0103140: C, 79.95; H. 9.39 Found: 0. 79.12; H. 8.71 Benzoate derivative. m.P. 80-82° 0. Fraction $111 from the acetylation was saponified 22 and 3.6 grams or material, boiling at 108-1100 C. at 3 mm., were recovered. Upon standing, crystals were obtained from this distillate, which melted from. 25-450 C. Recrystallization from petroleum.ether did not improve the melting point of this material. 'The,alpha-naphthylurethan derivative of this material was made. s.P. sci-205° c. The analysis for bro. mine by the Parr Bomb method showed 19.883 bromine. Theory for OZIHZOOZNBr, 20.07% bromine. , Para—t-butyl—o-bromophenol, made by bromination or p-t-butylphenol, gave an alpha-naphthylurethan which melted at 205-2060 C. The mixed melting point of these two ure- thans was soc-205° c. ' 23 3. Condensation of t-Amyl Alcohol With o-Bromophenol One half a mole (86.6 grams) of o-bromophenol and one half a mole (44 grams) of t-amyl alcohol were added to 200 m1. of anhydrous petroleum» ether. The solution was cooled with ice, the cooling was removed, and then 40 grams (0.6 x i mole) of anhydrous A1013 were slowly added, with the temperature of the reaction mixture being kept below 30° .C. The usual phenomena were observed. The reaction mixture was left to stir for eight hours at room temperature. The reaction mixture was worked up in the usual manner, dried, and the ether was removed. The residue from the other distillation was frac- tionated at reduced pressure. Fraction 3 I . 73° C. at 9mm. Fraction # II 72° C. at 9mm. - 110° C. at 2mmn, 54.0 grams Fraction #III 1100 C. at 2mm.*- 112° C. at 2mm. 40.3 grams f Material solidified in receiver. Fraction # IV Residue Fraction #11 was redistilled and 48.7 grams of ma- terial were collected at va-ao° c. at 12 mm. This fraction was analyzed'for bromine by the Carius method. Found, 42.70% bromine. Theory for o-bromophenol, 46.2% bromine. 0n the (basis that o-bromophenol was the only bromo compound pre- sent, this distillate nas 92.5% o—bromophenol. Fraction 3111 was analyzed for bromine by the Parr Bomb method and showed 7% bromine. 24 On the basis that only. p-t-amylphenol and p-to amyl-o-bromOphenol were present, the analysis that the ma- terial was 20% p—t-amyl-o-bromophenol and the yield of this compound was 6.6% of theory. The yield of p-t-amylphenol was 39% of theory. With the results from the bromine analysis, all of fraction #111 was acetylated and the resulting acetate mix- ture was distilled at reduced pressure. Fraction # 113° 0. at 1 mm. Fraction 5 11 ll3~110° c. at 1 mm.. 25.6 grams, n30: 1.5005 Fraction #111 116-1300 C. at 1 mm., 13.0 grams, Ego! 1.5070 a part of fraction $11 from the acetylation dis- tillation was saponified. The resulting crystals, after re- crystallization, were identified as p-teamylphenol. P-t-Amylphenol k m.P. 92-92.5° 0. Analysis. Calculated for 0113160: c, 80.44; H, 9.82‘ Found: 0. 80.27: H. 9.67 , Benzoate derivative. £.P. 58-60° 0. Fraction #111 from.the acetylation was redistilled and 6.6 grams of material, boiling at 123-124° c. at i-mm., n§° 2 1.5211 were obtained. This material was saponified with aqueous NaOH and heat. Upon distillation, 4.0 grams of phenolic material, boiling at 116-1180 C. at 2 mm., were recovered. 25 p-t-Amyl-o~bromophencl as? = 1.5507 Bio : 1.3168 Analysis. Calculated for 91131503”: Br, 32.87 Found: Br, 33.20 The alpha-naphthylurethan derivative of this ma- terial had a melting point of 149-150° 0. Analysis for bro- mine showed 18.81% bromine. Theory for szfiagozflBr, 19.38% bromine. Para~t~amyl~o-bromophenol,' made by bromination of p-t-amylphenol, gave an alphaonaphthylurethan which melted at 153-154° 0. The mixed melting point of these two urethane was 149-150° C. O 26 thsical Constants 0f the Fhenols and aoetates Involved in The Condensation of Tertiary Amyl and Tertiary Butyl Alcohols With Ortho-bromophenol Compound 8:361:38 173° 02° phenylacetate 704- 72° 0. 1.5036 mm. o-bromophenylacetate 101£- :320 C. 1.5393 p-t-butylphenylacetate 1213g‘::éo C. 1.4998 1.0188 p—t-amylphenylacetate 1213- 123° 0. 1.5000 0.9948 p-t-but‘yl-o-bromophenylacetate 1241; 126° 0. 1.5295 1.5092 mm. p-t-amyl-o-bromophenylacetate 1511- 32.? 0. 1.5273 1.2790 p~t-buty1-o~brom0phen01 1083-m;:o° C. 1.5446 1.2713 p-t-anyl-o—bronophenol 1162- 118° 0. 1.5507 1.3168 Billie p-t-butylphencl amuse-97° c. p-t-amylphenol M.P. 92° C. F. Acetylation of Phenols 27 The method of Chattaway (44) was used for making the acetates of the distillate mixtures. One tenth of a mole of the phenol was dissolved in an aqueous solution containing six grams (0.15 moles) of NaOH. The NaOH had been dissolved in enough water to barely give a liquid solution of the phenolate. The phenolate solu- tion was cooled, 50 grams of crushed ice were added, follow-l ed by the addition of 12.8 grams (0.125 moles) of acetic an- hydride. The solution was stirred for a minute or less, ether was added, and the two layers were separated. The aqueous layer was washed several times with ether and the combined other layers were washed with water. As the ace- tates are easily saponificd by a basic solution, according to Fischer and Grutzner, (45), it is necessary to wash the other layer as soon as possible to remove any base present. The acetylation mixture should be alkaline after the addi- tion of the acetic anhydride. Sufficient aqueous NaOH was added if the solution was not basic. Upon distillation, yields of acetates above 75% were obtained. The original phenol was recovered from.the acetate by addition of aqueous N803 to the acetate and heating on a steam bath until a clear solution resulted. The p-alkyl- phenylacetates were hydrolyzed very easily. The p~a1ky1~o~ bromophenylacetates needed a stronger basic solution to effect saponification. tore than 70% 0f the acetate is re- covered as the corresponding phenol. G. Derivatives 28 1. Diphenylurethans The method used for preparing these derivatives was exactly the same as given by Shriner and Fuson (46). 2. Benzoates One gram.of the phenol was added to a solution of three milliliters of pyridine and one milliliter of benzoyl chloride. The mixture was heated for three to four minutes and was then added to ten milliliters of ago. The water was -extracted with ethyl ether. The other layer was washed with dilute sulfuric acid, 10% sodium carbonate, and then ‘with water. Ethyl alcohol was added to the other layer and the ester crystallized by evaporation of excess solvent‘ and cooling. 3. Alphapnaphthylurethane One gram.of the phenol was added to one milliliter of alpha-naphthylisocyanate containing a few drops of an other solution of trimethylamine. The flask was stopped with a cork, to which was attached a drying tube. The flask was shaken and was then placed on the steam.bath to heat for ten to twenty minutes. Upon cooling, the solid mass which formed was heated with fifty to sixty milliliters of petrol- eum ether. The insoluble material was filtered off, and the urethan was recovered from the filtrate by evaporation of the excess solvent. D I SOUS {SI 32-! 29 In the cases where bromine is removed or replaced by a cationoid agent, removal seems to be most easily accomr plished when the bromine is ortho or para to a strong ortho- para director. Conversely, DeCrauu (47) has reviewed the re- placement of bromine by anionoid agents, such as ~0H, -OCH3, and ~NH2, and observed that halogen removal is easiest when the halogen is nets to a strong ortho.para director, or ortho-para to a mate director. His summary further showed that the halogens are replaced in the following order: F) 1) Br) Cl by a group such as ~03 or the ~00H3 group. Though the literature contains very little con- cerning the action of a101,3 on fluorine aromatics, it would seem that fluorine, bromine, and iodine, but not chlorine, are removed by the action of A1013. For an interpretation of the removal of bromine and halogen in aromatic compounds, and especially from.o- bromophenol, the cationoid theory of substitution, as out- lined by Price (48), offers the most logical explanation. In cationoid substitution, an electron deficient reagent replaces a proton in the benzene nucleus in the following manner: +[S=]+: x 5 + : -.S+ H+(I) - ‘ I;— Ehen the benzene ring undergoing substitution al- ready has an anionoid substituent present, the ease of 30 substitution is increased, due to the greater availability of electrons within the ring. Under such conditions, two or three cationoid agents may be added to the benzene ring in positions ortho and para to the directing and activating substituent. The second step of equation #1 is not readily re- versible when an inert solvent is used and the acidity of the solution is at a minimum. When benzene is brominated in an inert solvent, the HBr liberated is not acid enough to reverse the process causing debromination. When, however, a strong acid such as A1013 or 82804 is present, the second step is reversible and debromination can occur. In a similar manner, di- and trialkylaromatics can be dealkylated in the presence of a strong acid. A1013 has been found to be the most effective for dealkylation (17). In addition to the presence of both A1013 and pro- tons in the reaction mixture, the particular structure of o-bromOphenol may lend itself to debromination. In o-bromophenol, an electron tension may arise between the two substituted carbon atoms. Both hydroxyl and bromine are ring activators, bromine much less so than hy- droxyl, and each increases the electron density in the ortho and para positions in relation to its own position. As a result, a high electron density would arise between the two substituted carbon atoms. Under these conditions, a strong acid such as A1013 could attach itself to one of the elec- tron pairs betaeen these two carbon atoms, forming a dative 51 bond. The loss of the Br+ would then restore the aromatic ring character. A proton could then replace the n1013, either during the reaction, or upon hydrolysis with water and acid, with the formation of the debroninated product. ' H 0 Aids 1- x7: . + BY Ana, ., .+.}4 "“ fi-/\H:(3 ‘— OI 8:- AlCJs : I: 03: than debromination occurs in the presence of H2504, the proton adds directly to the aromatic ring. The net result, with either A1013 or H*, is the reverse of cat- ionoid substitution. filth bronobenzene and AICls-at 100° 0., it seems necessary to assume that it is the 31317 which adds to the a ring, for under these conditions, there would be little likelihood that a sufficient concentration of protons would be present to effect dehroninution. Gopisarou (10) showed that the passage, at a slow rate, of H01 or K” through a reaction mixture containing loo . 32 one mole of bromohenzene and amounts of AlCls up to sin- tenths of a mole of A1013, increased the extent of bromine removal and migration. When phenol was added to the reaction mixture to fix the bromine, the removal of bromine from bro- mobenzene was not improved, due to the reaction of the A1015 with the hydroxyl group. The writer found, however, that both of the o—halophenols, in the presence‘ of .1101:5 and a tertiary alcohol, at room temperature 'or below, did not evolve a significant quantity of HCl until fifty to sixty minutes after the addition of the first A1013. The presence of a hydroxyl group need not necessarily hinder the removal of bromine by A1013 from an aromatic nucleus, 11’ the reactim is carried out at a temoerature low enough so that the e- volved HCl is not removed as soon as it is formed. Whether it is 31013 itself, or protons, or a comp bination of both or these, which is the active agent in of- fecting debromination, cannot be determined with the pre- sent information. It suffices to say, at this time, that the debro- mination of cabromophenol is probably the result of two fac— tors: (l) The labile character of the bromine in o-bromo— phenol, and (2) The continued contact of o-bromophenol with a strong acid. 1. 2. 3. 33 SUIHARY Tertiary amyl and tertiary butyl alcohols 'condensed with ortho-chlorophenol at room temperature, in the pre- sence of aluminum chloride, to give fifty per cent yields of the correspOnding para—tartiary-alkyl-crtho— chlorOphenols Tertiary butyl alcohol and tertiary amyl alcohol both failed to condense with para-chlorOphenol, either at room temperature or at 60° C. Tertiary amyl and tertiary butyl alcohols reacted with ortho-bromophenol, in the presence of aluminum.chloride, to give, mainly, the corresponding pare-tertiary-alkyle phenol. Small amounts or the para-tertiarybalkyl-ortho- bromophenols were recovered, together with unidentified products. 1. 2. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 17. 18. 19. 20. 21. 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