m t OQWPimSAfIQ% OF HSPTYL ALCOHOLS WlfH WEMOt Ig JgS PEISMQg OF ALtJMXfOM CBhQRIPD A3 A GATALT8T A Dissertation submitted to the faculty of Michigan State College of Agriculture and Applied Science in partial fulfillment of the requirements for the degree of Doctor of Philosophy. by Glen Willard He&rlcfc June, 193? ProQuest Number: 10008478 All rights reserved INFORMATION TO ALL USERS The quality of this reproduction is dependent upon the quality of the copy submitted. In the unlikely event that the author did not send a complete manuscript and there are missing pages, these will be noted. Also, if material had to be removed, a note will indicate the deletion. uest. ProQuest 10008478 Published by ProQuest LLC (2016). Copyright of the Dissertation is held by the Author. All rights reserved. This work is protected against unauthorized copying under Title 17, United States Code Microform Edition © ProQuest LLC. ProQuest LLC. 789 East Eisenhower Parkway P.O. Box 1346 Ann Arbor, Ml 4 8 1 0 6 -1 3 4 6 acoqwledgmert To Dr. R. 0. Bustos, the writer wishes to acknowledge his sincere appreciation of his aid and guidance during the investigation of this problem. 331633 corruffs Page 3 ft II '"|l11* * 1 ' * ! '"'m * !■ Historical* **1 1*m **,>* XXX JV 0j,® OUS 3i IT '■' "II I IftM » M < p iW HHW IM M IP 4mm* ,(W I K ip f t W I W '*■ !H # 3 C ^ © X *X * '''»"■*III >IW*»***Ml—t »maw.1 1rnm-mmn.mmmmUfa■*,«»■»w«^ " * *»< M|ii. *"W.«P'»*■*>■nwrwi1m wiiiftMw**'**"*»» '* **ijmrnmni liniw mum i »mmy »i■*»•»»»»■—■*■■■wm*m-mmm+i w m fti^ S I* Isopropyl methyl ethyl o&rbinol--- — — — 28 3. Tert.~butyl dimethyl carbinol~~— — — — ^29 3• In-p?..— ..iw»■*■iw>ftft—I«»|m ■»■■<»■w»tpftiftmnnwi.ii«w.«■■—wwMft 4. Preparation of derivatives— — **— • — — — 34 5* Iltration of the tertiary heptyl ben?,en@s-35 6. Reduction of the p~nitro tertiary alkyl 21!OB© ************** 7* Phenols fro® p-araino tertiary alkyl hens 37 3. Oxidation of p-aitro tertiary alkyl ben&enes— — — ---- — — ----- 37 1 I*T8GD0enOS In the year 1916 Huston and Frie&emann (1) discover­ ed that aromatic alcohols condense with aromatic hydrocarbons in the presence of aluminum chloride as a catalyst* Since that time much work of this type has been don© In this laboratory* In 1866 Huston and Hsleh (3) reported the condensa­ tion of some simple tertiary aliphatic alcohols with phenol. To investigate further the scope of the reaction, the tertiary hepiyl alcohols were prepared and condensed with phenol using aluminum chloride as a catalyst. a HISTORICAL Many paper® have "keen written concerning the alkylation of phenols. There are two general methods for pre- paring alkyl phenols. They are, the alkyl&tion of phenols using alkyl halide®, acyl chlorides, alcohols, and alkenes in the presence of a variety of catalysts, and the prepar­ ation of phenols by the replacement of a variety of groups . by a hydroxyl in alkyl benzene derivatives. Alkyl phenols are also prepared by the rearrangement of alkyl phenyl ethers. Only those papers dealing with the condensation of alcohols with aromatic hydrocarbons using aluminum chloride as a catalyst are mentioned in this review, As far back as 18S4 Auer (3) and Dermatedt (4), re­ ported the Interaction of simple aliphatic alcohol® and phenols to give alkyl phenols using as a catalyst a mixture of zinc and zinc chloride. A little later $©£ (S) mention­ ed the formation of diphenylmethane from benzyl alcohol and benzene in the presence of aluminum chloride. In 191© Huston and Fried©maim (1) repeated the work of Ie£*s and reported that aromatic alcohols such as benzyl alcohol reacted with benzene in the presence of aluminum chloride to give a 30 per cent yield of diphenyl methane. 3 A few years later (1924), Huston (6) condensed benzyl alcohol with phenol in a similar manner as with benzene and obtained p-benzylphenol in a 45 per cent yield* This led to a further investigation concerning the scope of the reaction* Different types of alcohols were used, as well as different aromatic hydrocarbons* Huston (0) reported the condensation of benzyl alcohol with anisole and phenetole in a 45 and 50 per cent yield respec­ tively*. In 1936 Huston and Sager (?) attempted to condense phenylethyl-and phenylpropyl alcohols with benzene. result® were negative* The They concluded that of the aroma­ tic alcohols* only those in which the hydroxyl gfoup was on the carbon atom adjacent to a ring condense. They tried methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl and isoamyl alcohols, none of which condensed. They then tried allyl alcohol which condensed to give a 16 per cent yield. From this they concluded that only those alcohols in which the alpha carbon atom was a member of a benzene ring or is double-bonded, condense ~'ith benzene. Huston and Hewmann (8) followed this work by the condensation of allyl alcohol and phenol. later Huston and co-workers (9) reported the inter­ action of benzhydrol, methylphenyl and ehtylphenyl carbinols with phenol to give good yields of the condensation products. They pointed out that the experiments gave additional evidence of the effect of unsaturation of the alpha carbon atom on the reactivity of the alcoholic hydroxyl group for benzhydrol, in which both alpha carbons are members of an unsaturated benzene ring, gave a much larger yield than did benzyl alcohol* The condensation of an aromatic tertiary alcohol as triphenyl carbinol and phenol in the presence of aluminum chloride has not yet been reported* Although Davis (10) found that triphenyl oarbinol reacted with benzene to give triphenylmethane and not tetraphenylmethane. hater Huston (11} reported the condensation of benzyl alcohol with o-cr©eol, p-oresol, and m-eresol to give two mono subetituted derivatives and one disubstituted deriva­ tive for each* Huston and Qoodmoot (13) in 1933 carried out some experiments to -how the effect of strain in cycloalkyl earbinols on their reactivity with benzene in which they condensed cyclohexyl, cyclopentyl, and eyclobutyl oarbinol with benzene* They were able to show that the earbinols show a progressive increase in activity as the number of carbon atoms of the ring is reduced from six to four. Huston and Wilsey (13) found that 1, 1 - diphenylethyl earblmol did not condense with benzene, but instead dehy­ dration occurred producing 1, 1 - diphenyl - 1 - prooene. Huston and Hradel (14) and Huston and MacComber (15) in 5 soma similar work concluded that neither diaryl-alkyl earbinols nor dialkyl-aryl earbinols condense to give the desired product* Only dehydration of the alcohol occurr­ ed, All these experiments indicated that unsaturation or strain os the alpha carbon atom* whether it be doublebonded or a member of a benzene ring favors condensation reactions of aliphatic and aromatic alcohols with aromatic hydrocarbons and phenols or their ethers in the presence of aluminum chloride, Tery reeently Huston and co-workers have directed their efforts toward the condensation of some saturated aliphatic alcohols. In 1933 Huston and Hsieh (3) were interested in preparing some p-isopropylphenol. In their work they added isopropyl alcohol to a stirred mixture of aluminum chloride in an excess of benzene and it gave a fair yield of cumone. This was followed by more condensa­ tions reported by Huston and Fox {18} using some of the simpler tertiary alcohols and benzene. Huston and Bsieh (3) were successful in condensing some tertiary alcohols with phenol* toluene, m-xylene, m-cresylmethyl ether and anisole. They also condensed isopropyl and sec-butyl alcohols* methyl n-propyl oarbinol, and methyl isopropyl oarbinol with benzene, Huston and Binder (17) condensed the tertiary heptyl alcohols with benzene, Kuston and 6 Sculati (18), and Piston and Anderson (19) condensed some tertiary octyl alcohols with benzene and phenol. Tzu^rsranik (30) recently reported the condensation of some simple secondary and tertiary alcohols with benzene and toluene obtaining the same results as Huston and Hsieh (3) but offered a different mechanism which is to be dis­ cussed later. fhe only account of the condensation of heptyl alco­ hol with phenol is cowered by a patent taken out by McKesson and Bobbins (31 )t and McGreal and liederl (33) who con­ densed n-butyl dimethyl oarbinol with phenol In the pre­ sence of zinc chloride to giwe p-tertiary heptyl phenol. THEORETICAL From previous works Huston and co-workers have shown that for the condensations of alcohols, whether aromatic or aliphatic with aromatic hydrocarbons in the presence of aluminum chloride the alpha carbon atom must he understrain. If we examine the electronic structure of such a system, as for example allyl alcohol (A) or hensyl alcohol (B) and compare it with the electronic structure of a tertiary alcohol, as tertiary butyl alcohol (0) we will see why either are capable of condensation* In all three cases we have a carbon - oxygen bond that is relatively Z k unstable. G This is borne out experimentally by the ease of replacement of the hydroxyl group by the halogen of a halogen acid and also by the ease of dehydration. By vir- tu^e of the groups present the electron pair forming the carbon to oxygen bond of the first two is attracted strong­ ly by the carbon aton- and also by the hydroxyl group, and in the third the carbon has a weak attraction but the 3 hydroxyl has a strong attraction# The result in either case leads to an unstable system which for comparison are like the bonds in a molecule of chlorine (D) and a mole­ cule of hydrogen chloride (£) respectively. * • % * 4 : ci f ci: •» h With this in ( fox; ♦* •* 0 % view it is obvious that tertiary alcohols should condense with aromatic hydrocarbons the same as benzyl, allyl* benxhydrol, and the other alcohol® that have been shown to react. there have been four possible mechanisms advanced to explain the course of the reaction* none of which have been conclusively established. In many cases the different workers have used different catalysts, temperatures, and solvents thus leading to incongruous results. Tsuffervs&lk (20) reported the alkylation of benzene and toluene by use of secondary and tertiary alcohols in the presence of anhydrous aluminum chloride as a catalyst. He offered as a mechanism the formation of hydrogen chloride and an aluminum alcoholate (I) which decomposed to for® an alkene (12). The alkene then took up the hy­ drogen chloride to form the alkyl halide (III). This in turn reacted with the hydrocarbon to give the alkylated hydrocarbon If. This is represented by equations using tertiary butyl alcohol, benzene, and aluminum chloride* , (083)300® ♦ AICI3 I II A1C120Q(CH3)3— in CH3 oh3o' - 0% » aiox3ooCohs)3 ♦ HC1 CH-z GH3d — CEg T AlOIgOS (ch3)3c - 01 » set IT «m3)3o - CX T c6% — ► (oes)3c - C6E5t hoi If Tzu^ervanlk*e conception is correct the addition of a tertiary alcohol to a mixture of aluminum chloride suspended in an inert solvent should go through the first three steps to the formation of the alkyl chloride* Then the addition of phenol should lead to an alkyl phenol* To investigate the speclousity of the mechanism this was done* Sormal butyl dimethyl oarbinol in petroleum ether was added dropwise to aluminum chloride suspended in petroleum ether* Almost instantly hydrogen chloride was evolved and heat liberated* yellow then a deep red color. The mixture turned at first After the reaction had sub­ sided, a solution of phenol in petroleum ether was added dropwise. There was no further change in color nor any evidence of a read ion. After the usual procedure of decom­ position and purification to be described later an 18$ yield of n-butyl dimethyl-p-hydroxyphenylmethane was ob­ tained. This is a much smaller yield than was obtained with this alcohol in an ordinary run using the same mol­ ecular proportions. It should be noted that in the reaction of the 10 alcohol and aluminum chloride, hydrogen chloride was given off. this cannot be interpreted as following the mechanism offered by Tzultfervanik because in that hydrogen chloride was not given off until the hydrocarbon was added. k plausible explanation for the formation of hydrogen chloride in this reaction is in the dehydration .of the alcohol, and the water then reacting with the aluminum chloride according to the equations (?) and ?I). At the same time some of the hydrogen chloride might react with the alkene (?IT), v V2 ?XI In view of this it must have been the t t ^ O B a v j j ^ O H s£a&ons«3H2 )3 3 3 *1C13 t % C U — * AlClgOE T BC1 O0L 0H3{CH2)s - 8 s 0H3^ MCI—— f GH3(0E3)3-G Z 01 Gf% alkyl halide that reacted with the phenol to give the alkyl phenol, In addition it eeeme unlikely that the formation of an aluminate I is possible in view of the fact that It is not easy to replace the hydroxyl hydrogen of a tertiary alcohol* All this seems to indicate that the hypothesis set up by Tsujftervanlk is not probable. Another mechanism is offered by McKenna and Sowa (23). They have shown that when benzene is alkylated with alco­ hols using boron fluoride as a catalyst, the alcohol is first dehydrated and then the alkene condenses with ben2en© according to the following scheme (Till)* VIII CH^QSg^QM 4 BPg > OH^CHgO - GBg + CH3QH20H They state as evidence that normal and secondary alcohols give identical products and iso- and tertiary alcohols also give identical products* likewise liederl (33) has shown that dehydration of the alcohol is the first step in the reaction for when phenylethyl alcohol and phenol are treated with sine chloride 4 - hydroxy 1, 1 - diphenyl ethane is the chief product.. More evidence in favor of such a mechanism is in the condensation of unaaturnted hydrocarbons with aromatic hydrocarbons using aluminum chloride as a catalyst. Berry and Reid (34) have shown that ethylene condenses with benzene using this catalyst. Other workers similar to this are numerous (25). Evidence against such a mechanism is slight. It must be noted that McKenna and Sows, and Uiederl used a catalyst other than aluminum chloride and a much higher temperature than is employed in the Huston method. Huston and Sager (?) have shown that primary alcohols will not 13 r m ®t with benzene in the presence of aluminum chloride* the idea of ether formation followed by rearrangement to the substituted phenol presents itself as a possible mechanism. Much has been reported on the rearrangement of mixed aromatic ethers, the ether was formed in most eases by the alkali salt of the phenol and an alkyl halide Ux). XX OgHgOKe + SOX — > OgHgOH 4 H a d Most of the workers hare used agents other than aluminum chloride. R. Am Smith (34) report® the rearrangement of m-cresylisopropyl-^ether, tertiary butyl-*, isobutyl**, secondary butyl-*, and isopropyl-phenyl ethers, and p-cresyliso butyl ethers when treated in the cold with aluminum chloride (X). Re made the ethers by the above method (IX) and X % 0 0 O 6% -— $p-r3c*c6r4oh effected rearrangement by the addition of an equal mole­ cular amount of aluminum chloride. Re stated that the ethers could not be distilled even in vaeuo without re­ arrangement. Other works similar to this are numerous (3 6 ). In view of this it seems probable that if the alkyl ethers were formed as an intermediate they might rearrange to the alkyl phenols. The only accounts recorded in the literature of the formation of an ether by a catalyst similar to aluminum chloride are those of Serz and Weith (37), and Howland (28), the former in 1881 found that aluminum chloride reacted with phenol to give a 10 to 13 per cent yield of diphenyl ether at a reflux temperature. The former treated phenol in the presence of boron flu­ oride with methyl, ethyl and isopropyl alcohols. ethers and substituted ethers were obtained. The Isopropyl alcohol and phenol gave 2, 4-1sopropylphenylIsopropyl ether and 4-isopropylphenol* They found that dehydration was the first step in the progress of the reaction. Olalsen (39) pointed out that in alkylating the alkali salt of phenol with a halide of an uasaturated alkyl the ether is not a accessary intermediate for phenyl alkyl ethers under the conditions of formation do not re­ arrange to the alkyl phenols. He noticed that alkyl phenols were always present with the ethers. He states further that carbon-alkylatioo is still further increased if alkylphenols are used, that the solvent medium is most important, and that phenols with a vacant ortho position alkylate in that position. Thus allyl bromide and sodium ph©isolate in an alcohol medium give a 90 per cent yield of the allyl.ether but in a medium of benzene there is only a 30 per cent yield of the ether and a 70 per cent yield of o—allylphenol. This work of Claisen’s is in agreement with that of 14 Baaton*e for tee teas reported the condensation of tertiary alcohols witte benzene (XI}, anisole (XII), and m-cresyl— methyl ether (2) and ttee oondensation ofbenzyl alcohol witte anisole and phenetole (4)* XI xii R2COH - Ogfi6 * R30CgH5*r HgO r 3o o h — t o6e sooi% » r 3o * c 6h 4o c h 3 * b 2o In these, there is no possibility of ether formation however ttee reaction takes place giving a good yield of the alkylated hydrocarbon. To investigate ttee possibility of ether formation that might take place according to the reaction represent­ ed by equation XIII) ttee following was done, xiii ifter ttee r3coh t 06%GS~MS&%oeH5O G % ▼ % o reaction of a condensation was completed ttee mixture was decomposed witte water, acid and ice, and extracted with ether. Ttee ether layer was then washed three times with an excess of an alcoholic potassium hydroxide solution to remove the phenols. cold. Gar© was taken to keep ttee mixture Ttee ether layer was then dried and ttee ether eva­ porated off, Ho phenyl alkyl ethers were present. This would indicate that an ether was not formed m e n as an intermediate. Huston teas given as a possible mechanism ttee clea­ vage of water, ttee hydroxyl group of ttee alcohol and ttee para hydrogen of the aromatic ring being split off as is represented in equation (XIV), Aluminum chloride then appears to be merely a dehydrating agent. XIV This scheme is B30;0H"Vji C ^ O B J & B f y R g O - G6E40H f H30 unlikely for it cannot explain ttee fact that a highly colored complex always accompanies ttee reaction. Ttee proof of ttee mechanism for this reaction is beyond ttee scope of this thesis, but another mechanism that seems reasonable suggests itself. but some evidence for it. There is little, It is known that ferric chlor­ ide forms colored compounds with phenol. may be represented by equation (XV), Such a reaction it will seem more obvious when it is compared witte the reaction for the formation of the ferric cyanide ion or its acid as in equation (XVI). If we substitute aluminum chloride for ferric chloride an hydro-alnminum phenolic acid would re­ sult as in equation (XVXI), The hydro—aluminumpteeaoXic acid then reacts witte ttee alcohol (XVIII), to form an intermediate addition complex which rearranges (XIX) to give the substituted phenol and aluminum pteenolate. Ttee water formed in ttee step (XVIII) then would react with ttee aluminum pteenolate to produce 16 ordinary phenol and aluminum hydroxide (XX)* X? X?1 Fe013 f Fe013 -r SBGn 3 # f jFe(06gfig)^ f 3EGI 3H4* * [feQn^\ 3HG1 HOI3 + m O G ^ K ^ ± 3 # * m i XVII1 XIX XX Bo theory is % A 1 (0C6% ) 6 * 3E3GGH [ 4 1 ( 0 % % ) ^ “^ 3H01 AL(GG6H5}6.t-0%)3*3H2O AlXOGgllgJg-C^OEgJg— e AX(0G6E5)3 t 3H0CgH4. C % Al(O06% ) 3 ■* 3Ha0 — ■» A1(GK)3^ 3H0O6H5 offered for the rearrangement in the step represented by the equation (XIX) although it might he by the formation of the ether (XXI), XXI U the ether then rearranges quantitative- Al(0GgHg)6* C0R3 )3 zz± A1(0G6H5)3 f SEgOOC^Hg to the phenol as is represented by equation (XI). It is diffieult to visualize what would go on in a molecule so complex. The above scheme seems unwarranted but exper­ imental evidence gives some support to such a mechanism. Huston (6), to throw some light on the mode of con­ densation of phenol with benzyl alcohol, added aluminum chloride to a petroleum ether solution of phenol in the molecular ratio of 1 to 3. They obtained a colorless, viscous mass which solidified on standing. After decompo­ sition with water and hydrochloric acid the phenol was recovered. The reaction can be represented by XXII in which aluminum phenolate would be formed leaving an excess XXII 1 A1C1S * SCgH-gOH «*** A1(0C6H 5)3 * 1/3 AIGI3 of aluminum chloride. This work was repeated using the same relative quan­ tities# The evolution of hydrogen chloride was quite vig­ orous and some heat was liberated* Instead of decompo­ sing the reaction mixture at this point, a quantity of alcohol stoehlometrically equivalent to the phenol was add­ ed dropwiee. This represented the relative quantities of the ingredients in an ordinary condensation. the alcohol was added there was no color, nor any percep­ tible evidence of a reaction. After all of After decomposition and purification a 17 per cent yield of the alkylphenol was Obtained. This would indicate that the alcohol had re- acted with aluminum phenolate in the presence of an excess of aluminum chloride* However, this does not elim­ inate the possibility of the alcohol reacting with the aluminum hexo-phenolate for it might exist in a relative­ ly small quantity* This was followed by allowing phenol and aluminum chloride to react in a 6 to 1 molecular ratio as is re­ presented by equation X?II. the phenol as above* The chloride m s added to A little heat and much hydrogen chloride was evolved but there was no color. Toward the /' \ IS end the petroleum ether layer was clear and below it was a thick viscous mass that did not solidify* It did not resemble the aluminum phenolate above in any way. After the reaction had subsided, as evidenced by no perceptible evolution of hydrocarbon chloride, alcohol was added to the mixture in the ratio of 3 to 1 compared with the chloride or 1 to 3 compared with the phenol* Again there was no evidence of a reaction nor any color. However, after decomposition a 51 per cent yield of the alkyl phenol was obtained which agrees with the yields obtained with this alcohol in m ordinary condensation* From the above It is evident that using the consti­ tuents in the ratio as is represented in the equations (XY) to (XX) inclusive favors condensation. It seems log­ ical to suggest that the mechanism in an ordinary conden­ sation follows a scheme similar to that presented above* 19 DISCUSSION fiie general procedure employed in preparing the tertheptyl phenols consisted of the preparation of the terti­ ary heptyl alcohols followed by their condensation with phenol in the presence of aluminum chloride as a catalyst (mu). XXIII 07HlsOH . c 6h s o h o 7h 1s- c 6e 7o b t % o the alcohols that were thus condensed consisted of the foilowingt 1 - I-butyl dimethyl oarbinol, 2 - Isobutyl dimethyl oarbinol. 3 ~ Sec.-butyl dimethyl oarbinol. 4 - Tert-butyl dimethyl carbinol. § - H-propyl dimethyl oarbinol. 6 - Isopropyl dimethyl oarbinol. % 7 - Triethy1 oarbinol* These all have been prepared and reported in the litera­ ture. likewise Binder (17) prepared them and reported them. I-butyl dimethyl oarbinol has been prepared by Whitmore (30) by condensing n-buty!magnesium bromide and acetone. Isobutyl dimethyl oarbinol has been prepared by Edgar and co-workers (31) from i8obutylmagnesium bromide 20 and acetone* Secondary butyl dimethyl oarbinol has been prepared by Edgar (31) from secondary butylmagneeium bro­ mide and acetone« ðyl ethy1-n-propy1 oarbinol has been prepared by Whitmore (32) from n-propylmagnesium bromide and methyl ethyl ketone* Whitmore (32) and Edgar (31) prepared tert-butyl dimethyl oarbinol from tertbut ylmagne sium chloride and acetone, fri-ethyl oarbinol was prepared from ethylmgnesium bromide and diethyl car-* bonate. Isopropyl methyl ethyl oarbinol has been prepar­ ed from isopropyl bromide and methyl ethyl ketone by Whitmore and Evers (34). The above methods were used to prepare the alcohols for condensing purposes. the halides were made from the corresponding alcohols and phosphorous tribromide (35) in all cases, with the exception of ethyl bromide and ter-butyl chloride. Ethyl bromide was purchased and tert-butyl chloride was prepar­ ed from tert-butyl alcohol and concentrated hydrochloric acid. (36) the halides were then treated with magnesium and the ketone following generally the procedure of Whitmore (32). Good yields were obtained in all cases with the ex­ ception of tert-butyl dimethyl oarbinol and isopropyl methyl ethyl earblnol. It was apparent that as the bromide used became more complex the yield of the alcohol dimin­ ished tremendously, for this reason a more complex key- tone was sought so that a simple bromide might be used. 31 T^yi-^butyl dimethyl oarbinol was prepared by treating the ethyl ester of trim©thy1 acetic acid (3?) with methylmagneslum iodide. obtained. (XXIV}, a good yield of the alcohol was However, this involved using two soles of raethylmagnesium iodide so an attempt was made to condense XXIV (CS3)3CCr~ 002fi5 t 3CI2MgI— (0H3 )3c - f 2o a - f 5 ch3 pinacolone with methylmagnesium iodide (XXV). The alcohol, which consisted of a hydrate described by Whitmore (31}, was obtained in a 70 per cent yield. The solid hydrate was condensed as such with phenol. .0 X X VC 0 3htbyl urethanes were also prepared according to Shrin e r end Fuson (41}* The urethanes thus prepared were all solids and were readily recrystallisable from llgroin with the exception of the tertiary butyl derivative which was only slightly soluble in this solvent. reason it was not purified* For this The results are summarized in table IT, By observing the properties listed in the tables I, II# III, and X¥, it is obvious that of the seven phenols prepared they are all different. This indicates that the alkyl group of the alcohol combines with the benzene nucleus of the phenol without rearrangement. dece of this is shown in their melting points. More evlIt is known that the heaping of eurogene on adjacent carbon atoms of a compound causes an increase in the melting point of the compound, This fact Is in support of the structure of these phenols for as the heaping increases there is a decided, increase in the melting point. The absolute proof of the structure was established by synthesizing the phenols by another method* Binder (1?) prepared and definitely established the structure of the seven alkyl benzenes corresponding to the phenols report­ ed in this thesis by use of the psraehor, molecular refraction, and mol ecu! r volume measurements. In all cases 23 sec-butyl dimethyl^p-hy&roxyphenylmethane was prepared from sec-butyl dimethyl carbinol and phenol (XXVIIX); iaohutyl dimethyl-p-hydroxyphenyImethane was prepared from ieobutyl dimethyl carbinol and phenol (XXIX); tert-butyl dimethyl-p-hydroxyphetiyl me thane was prepared from tertbutyl dimethyl carbinol and phenol (ill); n-propyl methyl ethy1-p-hydroxyphenylmethane was prepared fro® n-propyl methyl ethyl carbinol and phenol (XXXI); isopropyl methyl ethyl-p-hydroxyphenyl methane was prepared from isopropyl carbinol and phenol (XXXIX); and trietbyl-phydroxyphenylmethane wae prepared from triethyl carbinol and phenol (XXXIII)* XXVII CS3CH2GE2GH2- Qn ^GH * CgHgGH__^GHjjGHgCKgGE2G-clH^OH-rHgO ‘ CI3 c6h4ge*b2q XXVIII ch2 XXIX ch 3c 2o c6h4oh - e2g i - O m G eB&OM ! “ 9% Ph3 *C%-GH -0 - G6H40H4H2O 'S83 26 the observed values agree with the calculated values* The phenols were prepared from these alkyl benzenes by the method of Senkowski (42) and Malherbe (43). The alkyl benzenes \>irere nitrated with fuming nitric acid, givin the para nitre derivative* The position was establ­ ished by oxidation of a portion of the nitro derivative with dilute hitrie acid in a Carius furnace (41}* lead, in every case, to p-nitro benzoic acid. This The more complex alkyl groups, as the tert-butyl dimethyl group, were very difftcul t to oxidise. The nitro groups were then reduced with tin and con­ centrated hydrochloric acid. This gave the p-tert-heptyl phenyl amines which were diasotised and hydrolysed to the desired alkyl phenols. The general procedure is repre­ sented in the series of equations (XXIf). The results are summarized in tables ¥ and ¥X. Tert-butyl dimethyl-p-hydroxyphenylmethane was recrystallized and identified by its melting point and a mixed melting point. The other phenols were identified by their 4 -aaphthyl uytilfetitft** Mixed melting points indicat­ ed that they were identical with the urethanes made from 27 the phenols obtained In the condensations. Thus the structure of each of the seren phenols n~ butyl dimethyl, isobutyl dimethyl, eec-butyl dimethyl, tert-butyl dimethyl, n-propyl methyl ethyl, isopropyl methyl ethyl-, and triethyl-p-hydroxyphenylmethane was established* 28 SXPERIlSSSm i g w m f t aaiaaai i m Thirty-six grams (1.5 moles) of dry magnesium turn­ ings and 200 cc. of anhydrous ether were placed in a erne— liter 3 necked flask equipped with a me rcury-aeal ed stirrer, a reflux condenser and a dropping funnel. To this 153*5 g (1*5 moles) of dry* redistilled ethyl bro­ mide was added with stirring through the dropping funnel at a rate fast enough to keep the mixture refluxing gently. After the addition was complete the stirring was continued for one hour at room temperature* Then 130 g (1*5 moles) of isopropyl methyl ketone, in 200 cc. of ether was added dropwise* The ketone was prepared from tert-asuyl carbinol (38) * After the ketone was ail added stirring was contin­ ued for two hours at room temperature then the mixture was cooled in an ice bath and poured on to ice in a large beaker. Dilute hydrochloric acid was added to dissolve the magnesium hydroxide. The ether layer was separated and dried for several hours over bonate. nfcydrous sodium car­ The ether was distilled on a steam bath and the resulting alcohol m s submitted to fractional,distillation 29 using a Claisea flask with an 18 inch fractionating column. Sighty-seven grams of the alcohol, boiling at 5G°20 52° (3Qps.), n 1*4283, was obtained which was 50 per 0 cent of the theoretical yield based on the ketone, I§fJr^yJL aiaiifeXi carbinol. 1 - From pinacolon© {44}. Twenty-two gram© (,8 mole) of magnesium turnings in 100 cc. of dry ether was placed in a 500 cc. round bottomed, 3-necked flask equipped with a mercury-sealed stirrer, reflux condenser and a dropping funnel. A mix­ ture of 138 g (.9 mole) of pinacolon© in 100 cc. of an­ hydrous ether in a 500 cc. round bottomed 5-necked flask equipped as above. When the Griguard reagent was &11 add­ ed stirring was continued for one hour, after which the mixture was decomposed and purified as in the case of iso­ propyl methyl ethyl carbinol above. Seventy-five grams of the alcohol, 71 per cent of the theoretical yield based on pinacolon©, boiling at 48°—51*® (3§aa«}, was obtained. This consisted of a mix- iure of colorless crystals (H«P. 80°) and a liquid which solifled when cooled in ice. This corresponds to th© carbinol described by Whitmore (32). The alcohol was us­ ed without further purification for the condensation with phenol* 30 2 •— From the ethyl ester of trimethyl acetic acid, the general procedure is the same as above. Hinety—nine and six tenths grams (*S moles) of methylm&gnesiuiB iodide in ISO cc, of ether was added dropwise to a stirred mixture of 35 g, (.3 mole) of the ester in 1G0 cc. of ether, After the complex was hydrolyzed and purified 28 g. of al oohol, 40 per cent of the theoretical yield, was obtained which had the same physical properties as that prepared from pinacolone. OondenaationeI the alcohol© were prepared as described and conden­ sed with phenols. In as much as all the condensations were carried out in a similar manner only a typical run is described her®. It should be noted that preliminary runs were made to determine the best procedure and the best relative quantities to use. Thus, for example, th© aluminum chloride m s added to a mixture of the alcohol and phenol, or a solution of th® alcohol and phenol was added to a suspension of aluminum chloride in petroleum ether. There was no difference in the yields obtained from either method and since th© latter method w$s more convenient it was employed* A slight excess of phenol was used in every case. Twenty-nine grams (,25 mole) of n-butyl dimethyl carbinol and 28 g. (.3 mole) of phenol dissolved in 1G0 cc. 31 of petroleum ether m s added dropwise with stirring over a period of two hours to 1? g, of aluminum chloride (.125 moles) suspended in 150 cc. of petroleum ether in a 500 oo* round bottomed flask equipped with a mercury-sealed stirrer* condenser and a dropping funnel* The addition was carried out at room temperature (20°-30°). A water bath was employed to Insure that the temperature would not rise above (20°-30°). After the addition was complete the bath was removed and stirring was continued for 4 to 6 hours* During all this time hydrogen chloride was given off and a deep red brown color developed. After allowing the mixture to stand over night it was treated with ice and hydrochloric acid. The hydrolyzed product was then extracted three times with ether and dried with anhydrous potassium sulfate. The ether was removed by distillation and the residue was fractioned by a modified Ol&isen flask using reduced pressure and an 18 inch fractionating column. There were three fractions* usually & small amount boiling from 40°-?0° at 30mm* was obtained which consisted of a mixture of the uncondensed alcohol, its chloride, and unsaturated compounds obtained from the alcohol; the next fraction consists chiefly of phenol boiling from 70°-llO° at torn,; and the last fraction was the desired alkyl phenol boiling from 110°—30° at 4mm. The last fraction was distilled repeatedly yielding a colorless liquid which solidified after cooling. Thirty- 32 one grams of the phenol or a 64,6 per cent of the theore­ tical yield based on the alcohol was obtained which melt­ ed at 16° and boiled at 123-5° (4mm,), 15?o~60° {l?aim.), and 2??° (748,5mm.). This particular phenol was not recrystalltzed. In­ stead the solid was pressed between filter paper to re­ move the oil, Th© other phenols, except the a-propyl derivative, were recryetal1ized from a 50 per cent mixture of alcohol and petroleum ether after they were distilled, Th© results are tabulated in table 1. for a study concerning the mechanism the following was done - all the reactions were run at room temperature. A. Twenty-three grams (.25 mole) of phenol was suspended in 100 cc. of petroleum ether in a set-up like the above and 17 g. (.125 moles) of aluminum chloride m s added in small portions. The mixture warmed up slightly and hydrogen chloride m s given off, mixture turned to a white solid. After a while the To this 29 g. (.35 moles) of n-butyl dimethyl carbinol in 100 cc. of petroleum ether was added dropwise. action, There was no evidence of a re­ The reaction mixture remained a white solid. This mixture after standing over night was decomposed and treated as in the general directions for decomposition and purification. The following fractions were obtained. (fractions on next page) 33 10 g. B.F. 40*60° (20mm.} alcohol, chloride, alkenes. 15 g. H 80-110° (4 * 10 g. * 120*30° * ) phenol. n n-butyl dimethyl-p-hy&rexy-phenylmethane. The yield was 25.6 per cent of the theoretical based on the alcohol. B. Thirty-five and two tenths (.3? mole) of phenol was supended in 100 cc. of petroleum ether as in the above and 3.2 g. (.062 iaole$ of aluminum chloride was added in small portions* ly. Hydrogen chloride was given off vigorous­ Toward the end of theaddition the mixture was clear and almost colorless. layers appeared. After standing a few minutes two The bottom layer was viscous possessing a light yellow color. To this mixture 14.5 grams (.134 moles) of n-butyl dimethyl carbinol in 100 cc. of petro­ leum ether was added dropwise. Ho color, nor any evidence of a reaction developed, but toward the end the lower viscous layer became more viscous. stand oversight and then decomposed# tions were obtained. This was allowed to The following frac­ The yield was 51.3 per cent of the theoretical based on the alcohol. 1 g. B.P. 2? g, * 15 g, H 40*60° (30mm.) 30-110° (4mm.) phenol 120-30° * n-butyl dimethyl-phy&roxy-phesyXmethane. C. Twenty-nine grams (.25 mole) of n-butyl dimethyl 34 carbinol is SO co. of petroleum ether was added dropwiae to 1? g. (.135 moles) of aluminum chloride suspended in 100 oe* of petroleum ether in a set-up like the one above. Hydrogen chloride was evolved at the start and a yellow color followed by a deep red color developed* After the addition was complete and the evolution of hydrogen chlor­ ide stopped, 38 g* (*3 mole) of phenol in 300 co. petro­ leum ether was added slowly* of a reaction* There was little evidence The color did not change. After decompo­ sition and purification 11 g, or an 18*8 per cent of the theoretical yield based on the alcohol was obtained. The following fractions were obtained. ?b g* B.P. 40-80° (30sm*) alcohol, chloride and alkene* 19.5 g. * 80-110° (4 * 11 g« ■ 130-30° 8 8 ) phenol. n-butyl dimethyl-p-hydroxyphenylmethane. Preparation of derivatives! A. Benzoyl and o-chlorobenzoyl esters of the ©even phenols were prepared by the method described by Shriner and Fuson (40). A typical run is as foil owe i Three grams of the phenol was dissolved in a 4 cc. of pyridine and 3 cc. of the acid chloride was added. After the initial reaction the mixture was warmed over a low flame, refluxed for one hour, cooled, poured on to ice with stirring, and extracted with ether. The ether extract was washed with acid to remove the pyridine, then 35 with sodium carbonate solution* After the removal of the ether the ester was distilled under reduced pressure and cooled in the ice box. the crystals thus obtained were re­ crystallised from 85 per cent alcohol and finally from 85-90 per cent §oetlc acid* The results are in tables II and III. B. ^-faphthyl Urethanes {415i One half gram of the tertiary heptyl phenol was plac­ ed in a 50 ec. dry Erlenmeyer flash with a pinch of anhy­ drous potassium carbonate and 1 cc* of anate was added. ~ naphthyl isocy­ A calcium chloride tube was placed in the flask and the mixture was heated on the steam bath for a few minutes. After cooling* 20 cc. of ligroin (80-90°) was added to extract the urethane. It was warmed to boil­ ing, filtered hot and a fine white crystalline product separated by cooling* The urethane was recrystallised from petroleum ether. The results are tabulated in table I?. nitration of the tertiary hentyj benzenes.(IT) The nitration m a carried out according to Malherbe's (43) procedure by treating the hydrocarbon with an equal weight of fuming nitric acid {1.53}. After the reaction subsided the mixture was warmed to 90° on & steam bath for one hour, then poured on to Ice. The nitro derivative thus prepared was extracted with ether then fractionally 36 distilled, fh© tertiary butyl dimethyl derivative was a solid which was reeryst&llised from alcohol, 411 the others war# liquids, the results are tabulated in table V* BffftWttlm 3l 1M para-nttro tertiary a i m fasozenes. The reduction of the seven p-nitrc tertiary alkyl benzenes above to the corresponding p-amino tertiary alkyl benzenes was accomplished by mean® of tin and hydrochloric acid, A typical run . 1® as fallows. Thirty grams of tin was placed in a 300 oc. round bottomed flask fitted with an air condenser. From 10 to 15 grams of p«nitro tertiary alkyl benzene m s added, then 100 cc, of concentrated hydrochloric acid was added in two portions* This mixture was placed on the ©team bath after the initial reaction subsided and left there several hours. '%e amine floated on the surface as an oil which solidi­ fied by cooling. This was probably a salt of tim descri­ bed by Ipatieff (45). This was treated with a large amount of wafer {£00 cc.) and mads alkaline with 40 per cent sodium hydroxide, then steam distilled from a liter flask* The amine was extract­ ed with ether, dried with solid potassium hydroxide and finally fractionally distilled using a email flask under reduced pressure. From Z to 5 grams of the amine was thus obtained, Th@ results are summarized in table VI, 3? fhmalB fro® oara m l m o tertiary alkyl benzenes (3), A typical diasotiaatfon la as follows# The amine CS g*} obtaia«d atofs wae treated with 1.5 cc. of concen­ trated sulfuric acid in 10 no# of water* The solid salt formed was then suspended in 100 to 150 cc. of water. After cooling it down to about S°$ a 35 per cent solution of sodiu® nitrite was added dropwise from a dropping fun­ nel with vigorous stirring until a positive test for ni­ trous acid was obtained with starch potassium iodide paper. The diasotised solution was then warmed on a steam hath and subjected to steam distillation. The phenol was ex­ tracted with ether, dried with anhydrous potassium sul­ fate and distilled in vacuo* After isolation in this way the of-naphthyl urethane was prepared using half of the phenol Obtained. The melting paints were the same as • those prepared from the phenols prepared by the previous­ ly described method. Hired melting point determinations gave no decrease in the melting points indicating that the phenols were identical with the other phenols. Cteldatioa. m r a - n l t m terti^X alkyl Mnaengg.. The oxidation method was adapted from Malherbe (43). One gram of the nitre compound and 30 cc. of dilute nitric acid (6 K*) was placed in a Carius tube, sealed and placed in the daxius combustion furnace. for two to six days. It was heated up to 13-0° By that time crystals formed in the tub® after it was cooled, The tube was opened, its con­ tents cooled is ice and collected on a filter, The white solid was washed with, ether and re©rystallized several times from alcohol. Is each case the crystals had a melting point of 338-240°. A mixed melting point deter­ mination with p-sltro benzoic acid shored no depression. 39 to s s s* o * © 8 <0 * s ' in a* m <3» to * p-t CO ef®3 i® c*s ©■ •rt fa fa. © #« o b >s© ■?55 fl t £0 rt O 9 *3 o * 40 TableXI Benzoyl esters Substance om positionfound.* P-Bydroxy-pbenylm eth&nes M .P . ..C ..& _a < 4b N-propyl m e t h y l ethyl 38*39° 80,40 j 8.18 W -butyl dim ethyl 38*37° 80*91 j 8.10 Isobutyl dim ethyl 71*72° 80.42 !i 8,12 Isopropyl m ethyl ethyl 40-41° 80.61 | 8*28 4 -t.» 4 .r 0 ■ *4 ■ J iw ly See*butyl dimethyl 00,89 j 8,00 Triethyl 74*75° 81,09 | 8.19 Tert*-butyl dim ethyl | 84*84,5° ...81•“ I 8.15 ♦Calc, for C ^gB g^O gt C , ia.03$j H , 8*1.6$ T&ble 221 Q -chlorobenzoyl esters* S ubstance P-Bydrory-phenylm ethanes M . P. 25*28° B-propyl m ethyl ethyl B-butyl dim ethyl 51*52° Isobutyl dim ethyl 43*43° Isopropyl m ethyl ethyl Seo*butyl dim ethyl 67-68° frlethyl 83-85° Tert, butyl dim ethyl ♦Calc, for O xeB jggO s& s Cl, 10.73$ . 8. P . $ 10.88 177-9° 10,71 10.63 10.58 i?5-8S 10.64 10.81 } 10.62 41 Table IV flaphthyX Urethanes. P-hydroxyph enylmethan es I. P. $ H Found.* 82-83° 3.84 110-11° 3.87 Isobutyl dimethyl 114-115° 3.78 Isopropyl methyl ethyl 112—113° Sec-butyl dimethyl 132—23 0 3.79 Triethyl 133-35° 3.91 K-propyl methyl ethyl H-biityX dimethyl ! 3.92 Tert.-butyl dimethyl »$• *Galo. for CX9% 402H: H, 3187# Table V and VI ?-»itro and p-amino tert.-heptyl benzenes P-bydroxyphenylmethanes' $~n i *T 0 'ter't.- (p-amino tert.. ASVUWO 0ft*jr* Mt B.P. r w a $ 5 m .f . B.P. (741) Found** "TI7=rflu 292 1-6.31 H-propyl methyl ethyl (5mm.1 6.98 ■[,ini1"" 111-' “TlgZ'S®"1 291 j6,31 1-butyl dimethyl ClGmm*) 7.22 .i . 284 S6*25 Isobutyl dimethyl 7,06 (5m®,} .1 285 6.24 Isopropyl methyl ethyl (llmrn*) 7,OX iSSPT® 377 l a . 28 Sec-butyl dimethyl (5m®,) 6.87 .DSPS!®1 288 6.30 7.21 Triethyl (5m®.) '' k.!\ =6.33 108° — Tert.-butyl dimethyl 55-56° —j.6.9 -.——.." ♦♦Gale, for % 3H 21.K: ♦Calc* for 8* 1, 7.174 i. i t i ii . n i. i.. i l i u m . j i.i n . m i. d ,i.ji nri 43 SUMMARY 1. the aliphatic tertiary heptyl alcohols have been condensed with phenol in the presenae of aluminum chloride to give good yields of the p-tertiary heptyl phenols. -at Z+. B-butyl dlmethyl-p-hydrexyphenylaethane, isobutyl dlffiethyl-p-hy&roxyphenylmethane, sec-butyl dimethyl-p-hydroxyphenylme tbane9 tert-butyl dimethyl-p-bydroxyphenylmethane, m-propyl methyl ethyl-p-hydroxyphenylmetbanet isopropyl methyl ethyX-p-hydroxyphenylmethane and triethylp-hy&r oxyphenylmethane have been prepared in this way. 3* The benzoyl, o-chlorobenzoyl esters and the naphthyl urethanes have been prepared. 4, sis. The structures have been established by synthe­ 43 BlBUGQBAmX I* Huston and Friedeuiann - J.A.C.S. 38, 8527 (1918)* 2, Hue ton and Bsieh - J.iUG.S. Jg|, 43© (18365. 3. Auer - B e n J£* 869 (1884), 4. Ber&siedt * Ben J£, 2569 <1880) , 5, lef ~ t o . 298, 255 (1897). S, Hasto * J.A.G.S, .48, 8775 (1834), 7, Huston and Sagftr • J.A.O.S. 1955 (1926), 8* Huston and Heroasn - Masters fhesle. Michigan State College, (1933), 9, Huston, Lewie and Grotemit - J.A.0,S. 49, 1305 (1927), 10, Huston and Davis - Masters Thesis. Michigan State College, (1933), 11. Huston and others - J.A.O.S. -53, 2379 (1831); 57, 4484 (193G); §4* 1506 (1932), ~~~ 12, Huston and Goodemoot — J.A.G.S, 58. 3432 (1834.) 13. Huston and Wileey * Masters Thesis, Michigan State College, (1833). 14, Huston and Bra&el *» Masters Thesis, Michigan State College, (1934). 15. Huston and MacComber - Masters Thesis. Michigan State College, (1835), 16, Huston and Fox * Masters Thesis. Michigan State College, (1934). 17. Huston and Binder - Masters Thesis. Michigan State College, (1935), 44 Hblicgraphy (contimied } 18* Huston stud SoulatX — if&etaye fhes 18 , Michigan State College, (1936). 19. Huston and Anderson * Mmefrerg Thesis. Michigan State College, (1930). 20. TraVervanik - J. Cten, Ghera. (tJ.S.S.R.) JL 117 (1935) C. A. 30, 443 (193$). 21. McKesson and Bobbins - G. A. |§, 15$ (1932) 22. MeOreal and Iledexl - J.A.C.S. 57, 2625 (1935). -23. MCKerma and Sowa - J.A.0.S. m , 470 (1836). 24. Berry and Held » J,A,C.S. is. 3142 (1927). 25. Varet and Vienne * Coopt* rend. 164. 1375 (1S86): dine and Held - J.A.G.3. 4&, 31TST(193?){ Gopenhaver and Reid - J.A.C.S. £g* 3157 (1927); Bodroux ~ Oompt, rend* 186. 1005(1928),. 26. Hiederl and Nat elson ~ J.A.0.3, fgL> i^28 (1931); S o m and Uiewlaad - J.A.C.S. 2010 (1038); B. A* Smith - J.A.C.S. §5, 4l"l933)|Olaisen — 2. angear* ohsm. 36. 478 (1983), Ber. 58 275 01925), Ann* 418. 6S-120 (ifTS); 3-arty and Adams - J.A.C.S, 57, 371 (1935); Siewland - J.A.G.3. £5, 340~1333). 27. Mers and faith * Bar* 188 (1881) 28. Hiewland - J.A.C.S. 57, 709 (1835). 29. Olaisen - A. angew* ahem. 36, 478 (1823). 30. Whitmore and Church - J.A.0.3. fj>5« 1X8 (1933). 31* ISdgar, Calingaert and Marker - J.A.C.S, 1483 (1889). 32. Whitmore and Ba&ertscher - J.A.0,3, 55. 1559 (1833). 33. Organic Synthesis XX. 93 (1831), 34. Whitmore and Steers - J.A.C.S. 55, 812 (1033). 35. Organic Synthesis 30 (1833). 45 Bibliography (continued) 38*. Organic Synthesis (Coll, ¥ol.) 138* 37. Organ!o Synthesis (Ooll. Vol.) 1, 510; Bar. 38, 839 (1905), 40, 4370 (1907) 38, Organic Synthesis m (1933). t-v,. 39. Shriner and Fuson — fhe Systematic Identification of Organic Compounds, p. 40, (1933) Edwards Brothers, inn Arbor, Michigan. 40, Shriner and fuson - Ibid, p* 63* 41, Shriner and Fuson - Ibid, p. 83. 42. Senfcowefci - Ber, 23, 3418 (1890), 43* Malherbe *» Ber, 53, 319 (ISIS), 44. Organic Synthesis JS, 87 (1925), 45. Ipatieff * J.A.C.S. 58, 1050 (1937). THE CONDENSATION OF THE TERTIARY HEPTYL ALCOHOLS WITH PHENOL IN THE PRESENCE OF ALUMINUM CHLORIDE AS A CATALYST The alcohols were prepared using an alkyl magnesium halide and a ketone. These alcohols were condensed with phenol using AlClg as a catalyst. The quantities of the alcohol, phenol and AICI3 used were in the ratio of 1 : 1.2 :o.5 respectively. / R - I- OH + HCgH40 E Equation: * R * C - C6H 40 H ♦ HgO The proof of the structure of the phenols consisted of preparing the phenol by another method which is illu­ strated by the following equations: Sn H HC1 . t tf-C-C6H4* KH3 f(-C-06H4-0H H « /Vl> E ° * Benzoyl, O-chlorobenzoyl esters and <<-naphthyl urethanes were prepared of the seven phenols.