I‘l'l 'T t GRlENTATlCN EN THE PHOSPHOPJC AGE-CATALYZED ALKYLATION OF ORTHO CRESOL Thesis for fine Degree 94‘ M. S. MICHEGAN STATE COLLEGE Edwin Alexander Hagiund “5949 This is to certify that the thesis entitled Orientation in the Phosphoric Acid-Catalyzed Alkylation of Ortho Cresol. presented by Edwin Alexander Haglund has been accepted towards fulfillment of the requirements for M. § . degree in M8117 Q Major professor Date Aug_st 22.1%9 ORIENTATION IN THE PHOSPHORIC ACID-CATALYZED.ALKYLATION OF ORTHO CRESCL BY Edwin Alexander Haglund A THISIS Submitted to the School of Graduate Studies of Michigan State College of Agriculture and Applied Science in partial fulfillment of the requirements ‘ for the degree of lmSTER OF SCIENCE Department of Chemistry 1949 gmmr mam. - '0- .' 1" r g , I. 1‘. I ' ’ p: ‘ .. “or“ / f. , ; HH-i» ACKNCWLEDGR‘ENT The subject of this problem was suggested by Doctor Harold Hart, under whose supervision and udth whose constant encouragement the work des- cribed was undertaken. The writer takes this opportunity to express his utmost appreciation. ********#* *t*#**** *****# ##1## ** :3 1218354. . . . I . . . r . n 't I i ’ ~ 1 . . t . .l n. a . i 7 I m ,l . s , o... L . OJ. TABLE OF CONTENTS INTRODUCTION.......................................... HISTORICAL............................................ EXPERIMENTAI~......................................... DISCUSSION OF RESULTS................................. SUTlfiICARYOOOOO0.0....0...OOOOOOIOOOOOOOOOOOOOO0.0.000... LITWATJRE CITEOOOOOOC0.000000IOIOOOOOOOOOO0.00...... Page 17 24 25 00.0.0.9... con-0.... . . 00.000.000.00. .0...’ ' INTRODUCTION The presence of bulky substituents ortho to the functional group has a pronounced effect upon the characteristic properties of phenols (1) and the synthesis of such substances is of considerable interest. In 1935, Chichibabin (2) reported the synthesis of thegt-butyl- ‘g-cresol by alkylation of gfcresol with Egrtfbutyl alcohol using a phosphoric acid catalyst. This resultis contrary to that obtained with other typical Friedel-Crafts catalysts, which give rise to 4etgrtfbutyl- ‘gfcresol (3, 4). It was considered of importance, therefore, to rein- vestigate the structure proposed by Chichibabin. If phosphoric acid actually does give rise to the ortho isomer, this would be an important synthetic method; if not, the error in the literature should be correct- ed. The problem was approached by using an independent, unambiguous method to synthesize 6ftggtfbutylggfcreeol. This product was then come pared with a sample of the product obtained from Chichibabin's proced- ure, with respect to physical and chemical properties and.ultradviolet absorption spectra. In this way it was possible to determine the cor- rect structure of Chichibabin's product. . .. .- . . I . . ,. , t 1”- . . ,. ’ l . ‘ I s . - ‘ “a I. o , i . I . . . . . t ’ i . s ' I . ' . - ' \ . . . ‘ , , 1 . . . r . . ' . . I . . . l r . v . vs . . I I I I . A ' I. . ' . . r . I t I ‘ ‘7 O ' '. - . a . I _ I , p . \ . I ’ l . . I I U , I ’ ‘ ‘ . II I . v w ' ‘- ‘P ~ ' . ' « . . I ‘ t x 'I I I v t ' \sa — .4 I" '3 . I ' .7 . ,- . . . I I I s: . I I ’ III . v r _ I o ' .“ , I o . ‘ \ r\ v .7 - ,_ I ‘ .'. . . , I, I I ‘ r u . 1 ‘- I I .i . HISTORICAL Since the present work is concerned with the orientation effect of phosphoric acid in Friedel-Crafts type condensations, it is well to revieW'briefly the previous use of this catalyst. In the alkylation of benzene with olefins in the presence of a sul- furic acid catalyst, excellent yields were usually obtained. In the presence of dialkyl esters of sulfuric acid which are formed during the reaction, the product could not be distilled, since decomposition occur- ed at approximately 120-130?C. As phosphoric acid catalytically decom- posed these alkyl sulphates, a quantity of the acid was added to the reaction.mixture with the result that no alkyl sulphates were found in the final product. When this process was found satisfactory, phosphoric acid was used alone by Corson and Ipatieff (5), with considerable success. A subsequent series of experiments, on the alkylation of various phenols at ordinary and superatmospheric pressures was carried out by Ipatieff, Pines and Komarewsky (5), with excellent yields of alkylated products being obtained. The phosphoric acid could be recovered un- changed and reused in the same manner; thus the phosphoric acid appeared to be a true catalyst. As phenolic ethers were also possible products, the experimental conditions were important. In general, elevated pres- sures favored ether formation. Some of the possible reactions between propylene and phenol are indicated in the following scheme: CH I 033 - CH 2 CH2 4 PO(OH)3 ———~ PO(OH)2-OC\/H 3 CH3 H ’ CH3 H — + Po(01~:)2-o-c( H —-—-—-> + PO(OH)3 CH 3 II III 'Pr OH 01 o + Clls-CH3CHZ HEPOQ @ H C iPr + CHE-CH:CHZ H'I P04 Q i r iPr In 1935, Chichibabin (2) published similar work on phosphoric acid catalyzed condensations. Some of his observations were: 1. 2. 4. 5. Phosphoric acid was an excellent condensing agent for the alkylation of phenols and their simple ethers with second- ary and tertiary alcohols, the better results being obtained with tertiary alcohols. Excellent yields were obtained even in cases where other agents gave unsatisfactory results. The only primary alcohol which gave good results was benzyl alcohol. Other primary alcohols required a temperature above that needed to cause isomerization to secondary and tertiary alcohols. . Good results were obtained using ethylenic hydrocarbons,I particularly when there was branching on the double bond. Secondary and tertiary alkyl halides may be used as alkylat- ing agents. Alkylation furnished principally the products containing the alkyl groups in the ortho position with respect to the pheno- lic hydroxyl group. At lower temperatures, only an insignifi- cant quantity of the para isomer was formed. 6. If equimolar quantities of reacting products were used, little or no dialkyl phenols were formed. 7. The presence of a substituent in the para position did not prevent the introduction of another alkyl group. 8. Ortho-cresol was alkylated very effectively by tggt-butyl alcohol. However, with benzyl alcohol, the principal product was a dibenzylfgfcresol (mixture of isomers) and a small amount of beenzyljg-cresol and still less of gfbenzylfigfcresol. 9. Small quantities of neutral products were formed, usually simple phenolic others. 10. The phosphoric acid, although it took part in the reaction, ‘was regenerated and could be recovered for future use. Though phosphoric acid is not generally considered a good catalyst for the formation of cyclic ketones, Koebner and Robinson (6) reported that 85% phosphoric acid was the best catalyst for the following cyclo- dehydration in the synthesis of x—Norequilenin.methyl ether. In 1938, Ipatieff (7) observed that the use of cyclohexane as a solvent at 2000 C. gage good yields of the alkylphenols, whereas with— out the cyclohexane, a considerable quantity of phenolic ethers were romedo Thus, propylene reacted with phenetole and phosphoric acid to form 02H5 H H / \ ~ This indicates the fact that an other is not necessarily an intermed- iate in the formation of C-alkyl phenols. Burwell and Archer condensed optically active (8) secondary butyl alcohol with benzene in the presence of phosphoric acid. The secondary butyl benzene had some Optical activity. It was noted that the rate of alky- lation was approximately equal to that of dehydration of secondary butanol in the absence of the benzene, indicating a common intermediate. Some modifications of the catalyst have been made successfully in recent years. Beyerstedt (9) added boron trifluoride to phosphoric acid, Mattox (10) and Ipatieff and Schmerling (11) used solid phos- phoric acid as a dehydrating and condensing agent. Ipatieff and Schmerling (12) later formed an alkylation catalyst by the interaction of ortho phosphoric acid and aluminum chloride in equivalent preportions. The mixture was heated to 800 C., whereupon hydrogen chloride was evolved, leaving a pale yellow powder, apparently Ulel-OPO(OH)2 plus unreacted aluminum chloride. Higher temperatures evolved more hydrogen chloride and reduced the activity. The catalyst was of the fluid type, did not form complexes with hydrocarbons and could be used for long periods without contamination. They also used solid phosphoric acid on kieselguhr, (13). ‘0 s5. Tsukervanik and Tambovtseva (14, 15) have recently used phosphorn: acid with success, even when the alkylating agents were primary alco- hols. Phenol and anisole were condensed with test-amyl alcohol at 70-800 C. , with iso-propyl and iso-butyl alcohols at {BO-100°C. and nor- mal propyl and butyl alcohols at 100-1300<3to form 80-95% of the para alkyl derivative with isomerization of the primary groups to secondary ones, and secondarngroups to tertiary. Small amounts of ortho deriva- tives were detected. Mbre recent modifications of ortho phosphoric acid catalyst in- clude gyro-phosphoric acid on kieselguhr (16), copper (or silver) pyro- phosphate‘with a supporting material, e.g. silica (l7), and mixtures of boron trifluoride with various phosphoric acids. -6- EXPERIMENTAL 4-Bromo-oeCresol (18) In a five liter, three-necked, round-bottomed flask fitted with a rubber stopper holding a mechanical stirrer, a reflux condenser, and a separatory funnel, were placed 500g. (4.63 moles) of g-cresol dissolved in 500-600 cc. of carbon disulfide. A calcium chloride tube was attached to the top of the condenser with a tube leading to a trap to take up the evolved hydrogen bromide. In the separatory funnel were placed 850 g. (5.3 moles) of bromine dissolved in 250 cc. of carbon disulfide. This was added to the reaction flask over a period of one and oneehalf-9 hours with constant stirring, the temperature being maintained at o-5°C. The carbon disulfide was distilled off on a steam.bath (care had to be taken because there was a large amount of hydrogen.bromide dissol- ved in the mixture). The residue was distilled through d Vigralx column under reduced pressure to separate the para bromo compound from the small amount of ortho bromo and dibromo derivatives of g-cresol formed. The main fraction was recrystallized three or more times from petroleum ether, with about 650 g. of white solid (m.p. 64°C.) (19) as the final product. IThis was 80% of the theoretical yield. Bromine analysis: By fusing (20) a weighed sample of the unknown with an excess of sodium peroxide in the presence of a small amount of potassium nitrate and sucrose in a "Parr" bomb, a solid mass was obtained. This was dis- solved in.water and the solution was acidified with nitric acid and heated until excess hydrogen peroxide was decomposed. An excess of standard silver nitrate solution was added and back titrated with stand- ard potassium thiocyanate using ferric alum indicator. Anal. CfilC'de for 07H BrO 3 Br, 42072 7 Found : Br, 42.75 4-Bromo-2-methylphenoxyacetic acid (21) A sample of 1.5 g. of 4-bromo-grcresol was treated with chloracetic acid in the presence of 55% sodium hydroxide and heated in a water bath for one hour. The product was separated by extraction first with ether and next with 5% sodium.carbonate. Upon acidification of the last ex- traction a white solid was separated from.the mixture. Upon recrystal- lization from ligroin a constant melting point of 122-30 C. was obtained. A weighed sample was dissolved in alcohol and titrated with standard sodium hydroxide using phenolphthalein indicator. Calc'd. for CBHBOBrCOOH : Neut. equiv., 245 Found : Neut. equiv., 245.3 Anal. Calc'd. for CQHQBrO3 : Br, 34.87 Found : Br, 34.78 4-Bromo-6-tert-butyl-o-cresol (Similar to sulfuric acid catalyzed alkylations in reference 22) For this preparation the alkylation vessel was made from an 10 inch test tube by installing a delivery tube in the bottom of it. It was similar to that shown in Fig. 1 of reference 22. With the vessel in a water bath and fitted with a stopper holding a condenser, a stirrer was extended through the condenser. Into this vessel were placed 140 g. -8- (0.75 moles) of 4-bromo-27cresol dissolved in 200 cc. of dry benzene. Five cc. of concentrated sulfuric acid were added as the catalyst. Isobutylene, which had been previously condensed in a dry ice trap, was placed in a flask with a delivery tube and the flask was sealed air- tight with beeswax. The delivery tube of the flask was connected to that of the vessel (air tight) with rubber tubing. Over a period of 5 hours, 78 g. (1.5 moles) of isobutylene were allowed to vaporize into the reaction mixture. The speed was controlled by occasionally immers- ing the flask in an ice-salt bath. The temperature of the reaction mix- ture was maintained at 65-7°C. with the water bath and high speed stir- ring maintained. Whem theladdition was completed, 50 cc. of benzene 'were added and the benzene solution was washed twice with 2% sodium hydroxide (100 ml. portions), then with sodium.chloride solutions until neutral to litmus. After drying the benzene solution over anhydrous sodium sulfate overnight, the benzene was stripped from the solution at room temperature under reduced pressure (water aspirator.) The residue was fractionated through a Vigreux column with 128 g. of product col- lected in the range 130-500. /llmm. This was 7075 of the theoretical yield based on the bromo-cresol. After several days this material (a liquid) began to crystallize. By slow tedious recrystallization from petroleum ether, a solid with a constant m.p. of 49-500C. was ob- tained. When equimolar quantities of isobutylene and bromo cresol were used, and when the gas was passed in at a greater rate (34 hours), the yield dropped to 30%. 'When a round-bottomed flask, with a capillary extending to the bottom was used, the yield was less than 10%. The prod- duct would not form anaryloxyacetic acid derivative with chloroacetic acid. -9- Anal. Calc'd. for 011H153T0 . Br. 32.89 Found . Br, 32.75 6-tert-butyl-o-cresol (Similar to preparation of o-tert- butylphenol in reference 1). In a one-liter round-bottomed flask with a reflux condenser (ground glass joints) were placed 11.1 g. (0.046 moles) of 4-bromo-6- test-butyltg-cresol, 50 cc. of ethanol and 30 g. of Haney-nickel-alumi- num alloy. Over a period of thirty to forty-five minutes, 500 cc. of 10% sodium hydroxide were added through the top of the condenser, with the mixture becoming hot enough to reflux. After the addition, the mixture was refluxed gently for one hour. The nickl} (solid residue) was removed by filtering the reaction mixture through a Buschner funnel while hot. The residual nickél in the funnel was washed once with 10% alkali and twice with benzene, and discarded. The water layer of the filtrate was cooled and slowly poured into 250 cc. of concentrated hy- drochloric acid. An oil layer formed, which was separated and added to the benzene washings from,above.' The water layer was extracted with 100 cc. of benzene which was added to the above benzene washings. This final benzene solution was dried over anhydrous sodium sulfate and the benzene was stripped at atmospheric pressure being a Vigreux column. The residue finally was distilled at 225-7° C.and a colorless liquid was obtained weighing 6.9 g. or 92% of the theoretical yield. This compound also failed to yield an aryloxyacetic acid deriva- tive under the procedure used preViously. It would not dissolve in 10% sodium hydroxide, nor give a color when treated with alcohol and ferric chloride solution. It did, however, dissolve in Claisen solution. -10- When treated with phosphomolybdic acid and ammonia it gave a greenish blue color (22) Anal. Calc'd. for C113160 3 C, 80.3 ; H, 9.80 Found : C, 80.34 H, 10.08 Rearrangement of 6-tert-Buty1-c-cresol To one cc. of S-EEEEfbutylegfcresol were added 5 drops of concen- trated sulfuric acid. The homogeneous mixture was warmed gently in a flame for two or three mdnutess then poured into cold water. The oily layer which formed was taken.up with petroleum ether, the ether layer washed with sodium carbonate solution and then dried over calcium chlor- ide. Upon evaporation of the ether, a solid remained which was soluble in 2% sodium hydroxide. It also reacted with chloracetic acid to form araryloxyacetic acid derivative. After isolation of the product and recrystallization from.ligroin, a solid derivative formed with a melt- ing point of 101.5-102° c. CEIC'd. for 0121117OCOOH 3 NWt. equiv., 222 Found : Neat. equiv., 221.1 Two cc. of Bgtgrtfbutylfg-cresol were treated with 100% phosphoric acid at 65-700 0. with constant stirring. After eight hours the mix- turerwas cooled, poured into cold water, and extracted with petroleum ether. After extraction of the other layer with 2% sodium hydroxide, the water layer was acidified and extracted with ether. The ether layer was washed with sodium carbonate, dried over calcium.chloride and the ether was slowly evaporated. The liquid residue reacted with chloracetic -11- acid in the same manner as above to form.a solid melting at 97-100o C. Upon evaporation of the original petroleum ether layer, a liquid resi- due, which did not dissolve in 10% sodium hydroxide, was left. This was assumed to be unchanged starting material. Alkylation of o-cresol; Chichibabin's Procedure (2) Into a two liter round-bottomed flask equipped with a stirrer, con- denser, separatory funnel, and a Glas-col mantle, a mixture of 54 g. (0.4 mole) of g-cresol anleO g. of 100% phosphoric acid was? placed. Into the separatory funnel, a mixture of 100 g. of 100% phosphoric acid and 40 g. (0.54 moles) of teat-butyl alcohol'wlSh placed. 'With the temperature of the mixture in the flask maintained at 600150 c. and with this mixture stirred continuously, the contents of the separatory funnel were added over a period of three hours. Then the mixture was stirred for five more hours at the same temperature. Instead of using Chichibabin's long involved methods of separation, a shorter conventional one was used. The contents of the reaction flask were cooled and poured into 2 liters of cold water, after which the mix- ture was extracted twice with 100 cc. portions of ether. The combined ether layers were then treated with 10% sodium.hydroxide and the water layer was acidified and extracted once more with ether. The other layer was dried over calcium chloride, the ether stripped slowly at atmospheric pressure. The residue was fractionated carefully at atmospheric pressure. A colorless liquid boiling at 235-7o C. was the main product. It was found to weigh 52 g. or was 62% of the theoretical yield. A higher fraction not purified was thought to be a dialkyl derivative. Upon -12- ‘1 second treatment of the first other layer with 10% sodium.hydroxide and acidification of the water layer and finally extracting this acidic solution with ether, 8 g. more of the product boiling at 255-7o C. were obtained. This product was treated with chloracetic acid in the procedure previously used and a compound was obtained with a melting point of 101.5-102o C. This solid, when mixed with a sample of the aryloxyace- tic acid derivative of the rearranged Sfitggt-butyleg-cresol, melted at 97-100° c. Calc'd. for C12H17OCOOH : Neut. equiv., 222- Found 3 Neut. equiv., 221.5 The alkylation product gave a blue color upon dissolving it in ethanol and adding ferric chloride solution. When treated with phos- phomolybdic acid and concentrated ammonium hydroxide solution, a deep blue color appeared. The ultraviolet absorption spectra were determined with a Beckman spectrophotometer, model DU, using 1 cm. quartz cells. Solutions of the following compounds in cyclohexane were run: 4-tert-butyl-o-cresol (alkylation product) §:tert-butyl-o-cresol 4,6-di-tert-buty1-o-cresol The data obtained is given in tables, I, II, and III. -13- TABLE I Ultra-Violet Absorption Spectrum of 4-tert-Butyle2-Cresol in Cyclo- hexane - 2.?55-10"4 Molar lull d e 300 0.007 30 295 0.009 - 38 290 0.037 157 288 0.089 378 286 0.217 923 285 0.303 1289 284 0.387 1647 283 0.450 1911 282 0.460 1957 281 0.437 _1860 280 0.428 1817 279 0.446 1898 278 0.482 2047 277 0.512 2179 276 0.527 2200 275 0.508 2162 274 0.497 2115 273 0.483 2051 272 0.460 1957 271 0.431 1838 270 0.407 1732 269 0.383 1630 268 0.363 1545 267 0.341 1451 266 0.313 1332 265 0.288 1221 264 0.259 1102 263 0.237 1008 262 0.214 911 261 g 0.193 821 260 0.173 736 258 0.124 529 256 0.102 434 254 0.071 302 252 0.047 200 250 0.034 145 245 0.003 21 240 0.014 60 235 0.099 421 232 0.267 1136 230 0.476 2025 228 0.772 3285 -14— TABLE II Ultra-Violet Absorption Spectrum of 6-tert-Butyl-o-cresol in Cyclo- hexane 2.67-16'4 M01ar m/u d 6 300 ' 0.001 4 295 0.003 12 290 0.008 30 288 0.013 49 286 0.024 90 285 0.038 142 284 0.055 206 283 0.084 315 282 0.128 479 281 0.188 704 280 0.268 1004 279 0.356 1337 278 0.448 1678 277 0.500 1876 276 0.497 1861 275 0.468 1757 274 0.457 1715 273 0.465 1745 272 0.479 1798 271 0.494 1850 270 0.498 1865 269 0.478 1794 268 0.474 1775 267 0.448 1678 266 0.413 1547 265 0.382 1431 264 0.356 1333 263 0.333 1247 262 0.309 1157 261 0.283 1060 260 0.258 966 258 0.206 775 256 0.161 603 254 0.117 438 252 0.081 303 250 0.058 217 245 0.012 45 240 0.003 12 235 0.045 169 232 0.132 494 230 0.253 948 228 0.465 1708 -15.. .~.. a . -7- --.. TABLE III UltraeViolet Absorption Spectrum of 446 di-tert-Butyl-o—cresol in Cyclohexane 2.37010“ Melar my: d E 300 0 0 295 0.005 22 290 0.044 186 288 0.095 397 286 0.201 886 285 0.292' 1232 284 0.381 1608 283 0.468 1979 282 0.528 2232 281 0.557 2355 280 0.565 2384 279 0.568 2397 278 0.576 2435 277 0.589 2490 276 0.602 2540 275 0.605 2557 274 0.604 2549 273 0.593 2502 272 0.572 2418 271 0.543 2291 270 0.508 2144 269 0.476 2013 268 0.447 1886 267 0.417 1760 266 0.409 1729 265 0.354 1498 264 0.326 1377 263 0.294 1249 262 0.268 1131 261 0.241 1071 260 0.218 :920 258 0.171 722 256 0.132 557 254 0.092 388 252 0.063 266 250 0.044 186 245 0.009 38 240 0.015 64 235 0.128 540 232 0.346 1464 230 0.597 2511 228 0.915 3865 -16— DISCUSSION OF RESULTS The product obtained from the phosphoric acid catalyzed alkyla- tion of g-cresol with testfbutyl alcohol has been assigned the struc- ture 6fteztfbutyljgfcresol by Chichibabin (2). 0H L“ ,/ (CH5)3 C H3 7 _ I i Compound I \\_ This is contrary to the results obtained when using other Friedel- Crafts catalysts. Baur (3), for example, obtained 4ftggt-butylfgf cresol using zinc chloride. Petty (4) obtained this same compound with an aluminum chloride catalyst. 0H 0 C(0H3)5 Compound II Compound I was synthesized according to the following scheme: H OH CH B , 3 r2 H3 isobutylene CS2 5 H2304 Br 70% Yield 80% Yield (CH3)3-C- I Raney's Alloy T—E|.O% NaOH 92% Yield With compounds similar to I, there is a tendency for the bulky group to migrate from the ortho to the para position in the presence of acid -17- catalysts. A good example of this rearrangement was shown with .gfitggtfbutylphenol (1). This rearrangement was also carried out with Compound I. As sulfuric acid or phosphoric acid catalyzed this rear- rangement, it was important that the last step of the above scheme was carried out under alkaline conditions. This unique process allowed replacement of the'bromine atom.of III by hydrogen without this migra- tion or without formation of any other undesirable side products. Compound I (Sftggtfbutyl-gfcresol) was not soluble in 10% sodium hydroxide. Upon dissolving it in alcohol and adding ferric chloride solution, no color appeared. It did not form an aryloxyacetic acid after a tratment with chloroacetic acid. The above properties are characteristics of phenols and asil did not exhibit them it was classed as a hindered (or partially hindered) phenol (22,23). Its boiling point was 100 C. below that of 4fitg£tfbutyl-2§cresol listed in the lit- erature (3). This compound, however, gave a color when dissolved in alcohol and treated on a spot plate with phosphomolybdic acid and concentrated ammonium.hydroxide. This is a very sensitive test for phenols and even 2&4,5:tri-tert-butyl phenol gave this positive test (22). This fact along with the evolution of hydrogen gas on treatment of I with metal- lic sodium indicated that I was not an ether. The ultraviolet absorp- tion spectrum (See figure I) is also very similar to that of phenol. An authentic ether of this sort was synthesized by McKinley (24). It was formed throughsreaction involving a Grignard reagent and only under extreme conditions. The yield was very low (10% or less). It -18... - 7‘ .. was shown that this ether rearranged readily to an alkyl phenol under conditions used in the preparation of Compound III. Its spectrum exhibited no peaks like those (Fig. I) characteristic of phenols. With the exception of Chichibabin's paper, no preparation of G-tgrtfbutylggfcresol appeared in the literature. However, Whitaker (a5) did report a hydrogenation of this compound to form.6fitgrtgbuty1- Z-methylcyclohexanol (B. P.--103.5-107° c./2o mm.), and Pardee and weinrich (26) reported a number of physical properties of Bert-butylfig- cresol (two different isomers were mentioned with the position of the tertfbutyl group not mentioned). However, neither of these reports indicated the source of this particular compound. Upon alkylation of g-cresol using Chichibabin's procedure (2), a product was obtained that was very soluble in 2% alkali, that gave a color when treated with ferric chloride and with phosphomolybdic acid and ammonium hydroxide. It formed an aryloxyacetic acid deriva- tive when treated with chloroacetic acid. The ultraviolet spectrum showed the shift of about 6 mp. toward the longer wavelengths (table IV a Fig. I) which is characteristic of p-alkylphenols. The boiling point 235-7° C. (atmospheric pressure) is the same as that of 4'EEEE‘ butyl-o-cresol reported by Baur (3). In the presence of either sulfuric or phosphoric acid Compound I (Setgzt-butyleg-cresol) rearranged to form a different compound. This new compound did not exhibit any of the properties of the original compound that were characteristic of hindered phenols. It was soluble in dilute alkali, formed a color with ferric chloride, and readily formed an aryloxyacetic acid derivative. This derivative was compared to the aryloxyacetic acid derivative of the above discussed alkyla- tion product and they were found to have the same melting points and neutral equivalent numbers. After a mixture of the two gave this same melting point, it was concluded that these two derivatives were identi- cal compounds. As shown above, there is a tendency for bulky groups in the ortho position to migrate to the para position (if it is open) in the presence of catalysts such as sulfuric or phosphoric acid. Thus the following equation illustrates the reaction: OH (CH5) 5CK.CH3 H P0 3 4 \ ——-—-—.> From the above fact, it can be seen that under the conditions of Chi- chibabin's alkylation, considerable rearrangement would take place if the ortho isomer were actually formed. Hence it was concluded that the alkylation product of Chichibabin is 4123£tfbutylegfcresol (Compound II) and not Setggtfbutylfgfcresol (Compound I). The peaks in the ultra-violet absorption spectra of 4722537butyl' ‘g-cresol and of GjEEEEfbutyljg-cresol are compared in Figure I. By consulting Table IV, the shift of the former can be clearly seen. This table shows the peaks of some phenols and includes examples of gfalkyl and p-alkyl substituted compounds along with phenol itself. Thus in general, gfalkyl phenols have peaks very similar to phenol, while p-alkyl phenols show an approximately 6 myz. shift toward the longer wavelengths. -20- TABLE IV Maxima in the Ultraviolet Absorption of Some Phenols Peak 1 m/u e Phenol 271 2130 gfcresol 271 2140 2:2352f8uty1phenol 271 2014 BfEEEEfButylfig-cresol 270 1865 aforesol 278 2160 pftgzthutylphenol 277 2130 4-tert-Buty1-o-cresol 276 2200 (Alkylation Product) 4,6-di-tgzt-butylg2-cresol 275 2557 Key to Fig. I 4-tert-butyl-o-cresol 6§tert-butyl-27cresol -.-.-.- 4,6-di—tert-butyl-o- ------ cresol -21... Peak 2 In}! ¢ 278 1847 278 2040 278 2018 277 1876 284 1860 283 2054 282 1957 (280) 2384 Ref. 27 Fig. I 27 Fig. I Fig. I FIGURE I 240 1 Q \.\ ‘0 \‘Ie|"-|-"‘ellu ‘‘‘‘‘‘‘‘‘‘‘‘‘‘‘‘ ‘0 \_ ............... ll ‘\ eeeeeeeeeeeeeeeee “‘ “0‘0 ‘ O, a o, ’I""' ob """""" l """" 0,. le”,"' 1 I.h"' e/eI’I ’ollo'l” .11: ll .fl” .4 f “" e\e ‘‘‘‘‘ o\ ......... 0‘ '''''''''' ‘C‘ ............. ' ‘ '0‘. ---'----“|'-'.-" I-‘II‘II. | ‘ ‘ | ‘ ‘ ‘ '0'.‘ | ' ' | 1 AU AU AU AU AV 0 0 O O ‘9 nu Ru AU AU 2 2 I I 5 A WV ”3303.300 acaponwpxo asaoz 280 300 260 . Wave length (my) Key given on previous page. -22- This shift also occurs with 4,6-diitgit-butyljg-cresol. The peaks are broader and more overlapped (Fig. I) as one would expect with a more highly substituted compound. This shift shows that the p-alkyl shift occurs even when the phenolic hydroxylgroup is sterically hind- ered by such bulky groups. -23.. SUMMARY 1. The product obtained from the phosphoric acid catalyzed alkyla- tion of aforesol with tgitfbutyl alcohol is actually 41:213'bUty1f2f cresol (compound II) and not GfiEEEE-butyl-gfcresol as claimed by Chichibabin. This was established by an independent unambigius syn- thesis of SfEZEEfbutyljg-cresol and a comparison of the physical and chemical properties of this product with that obtained by Chichibabin's direct alkylation procedure. 2. The‘ultraeviolet absorption spectra of the compounds have been determined and discussed. -24- 13. 14. 15. 16. 17. 18. REFERRJCES CITED Hart, H., J. Am. Chem. fipc:, 71, 1966 (1949). Chichibabin, A. 3., £911._90o. Chem. (5) 2 497-520, (1935); Compt. rend. 199, 1239 (1034). Rear, A., Ber. 27, 1615 (1294). Petty, R. H., Thesis for U. 3., M. S. C.; 2-7, 19-20; (1937). Ipatieff, Vladimer N., Catalytic Reactions at High Pressures and Temperatures; New York, The “homilian Company. 1936. pp. 659-673. Koebner, 4., and 3. Robinson, J. Chem. Soc., 1994 (1932). Ipatieff, V. N., H. Pines, and L. Schmerling, J. Am. Chem. Soc., eg, 1161 (1938). Burwell, R. L. Jr., and S. Archer, J. Am. Chem. Soc., 64, 1032 (1942). ”"— ‘- 3 U. 3. Pat. 2,363,222; C. A., g3, 3007 (1945). Hattox, w. J., Trans. Am. Inst. Chem. Eng:§., 41, 463 (1945). U. 3. Pat. 2,374,600; g;§., pg, 35331 (1945). . D U. 3. Pat. 2,402,051; 0.1., 39, 4959“ (1946). Ipatieff, V. N. and L. Schmerling, Ind. Eng. Ch?§;9.§§2 400 (1945). ’“’ Tsukervanik, 1., J. Gen. Chem:.(”.3.3.?:), ii, 699 (1945) (English Summary); 0.4., 40, 57073 (I946). Tamboutseva, V. and I. Tsukervanik, J. Gen. Chem. (U.S.S.R.), 12, 920 (1945); C.A., 41, 732C (1947). U. 3. Pat. 2,456,490; 0.4.. pg, 5029‘ (1925) U. 3. Pat. 2,312,229; C.A., 3;, 1u21h (19u7) Prepared by method for p-hromo phenol in Organic Synthesis, Coll. Vol. I, John Wiley and Sons, Inc., NeW'York, N.Y., 1941, p. 128. Edition II. -25... O c Q I . . I n v e to t. O . t r . v' I O ' . t .- I '. . U \ t _ . I . C u C ' V I I O I C . V ‘ o o t I ‘ $ | \ . o O I I. 9- {I O 0 g e a O . I I. C o I O Q .g o ' l p n '7 a O J p O 21. 22. 23. 24. 25. 26. 27. Heilbron, I. M., Dictionary of Organic Compounds, Oxford University Press, New York, E. Y., 1943, Vol. I, p. 284. Lemp, J. F., and H. J. Broderson, J. Am. Chem. 809., 32, 2069 (1917). Shriner, R. L. and-R. C. Fuson, The Systematic Identification of Organic Compounds; New York, W.Y., John Wiley and.Sons, Inc., (1946), p.174. Edition II. Stillson, G. H., D.‘W. Sawyer, and C. K. Hunt, J. Am. Chem. Soc., 67, 303 (1945). Coggeshall, N. D., and E. M. Lang, J. Am. Chem;_Soc., 70, 3283 (1948) "’77' ‘— MCKinley, J. 9., J. Am. Chem. Soc., 69, 1624 (1947). Whitaker, A. C., J. Am. Chem. Soc., 69, 2414 (1947). Pardee, W. A., and W. Weinrich, Ipd. Eng. Chem., 36, 595 (1944). Wolf, K. L., and'W. Herold, g: Physik. Chem., (B) 133 201 (1931). -25- 218354 Haglund Orientation in the phosphoric ac id-catalyzed alkylation of ortho cresol Mm V“ . _I ll ‘lnll l’E‘