THF, CONDENSATION OF SOME DIALKYL ARYL CARBINOLS KITH BENZENE AND PHENOL IN THE PRESENCE OF ALUMINUM CHLORIDE by FRANCIS ALOYSIUS HUGHES A THESIS Submitted to the Graduate School of Michigan State College of Agriculture and Applied Science in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY Department of Chemistry 1940 ACiaiOWLKDGMENT mv,o G,Uv"w^~iQX* v^f.'ViDc’ ~ho o v n v o « o thanks to Dr. H. C. Huston for hi guidance in this work. Table of Contents Page Introduction -- _ _ _ _ _ ----- ]_ j> Theoretical 5 - Historical _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ Experimental 10 Materials--- _ _ _ _ _ _ _ _ _ _ _ ---Carbinols - - - - - - - -- _ _ _ _ 10 _ Condensations — Identification - 14 ---- --- Proof of Structure _ _ _ _ _ _ _ _ _ _ --- Synthesis of Dimers Discussion Summary 18 25 26 - _ _ _ _ Bibliography - n - --- _____ ---_ _ _ _ ----- 54 40 41 1 Introduction In this laboratory, since 1916, Huston and co—workers have worked with the condensation of alcohols with benzene and phenol in the pre­ sence of aluminum chloride. They have investigated the primary, secondary, and tertiary aliphatic alcohols. In the aromatic series of alcohols, they have also included the primary, secondary, and tertiary. In continuing the study of aluminum chloride condensations, the mixed aliphatic-aromatic alcohols are under investigation. Some di­ alkyl aryl alcohols were condensed with benzene and phenol in the presence of aluminum chloride. 2 Historical Condensation reactions, in which alcohols and various compounds combine, have been known for quite some time. brought about by the use of a catalyst. The reactions are A great number of catalysts have been employed; namely, zinc chloride, sulfuric acid, magnesium chloride, acetic acid, phosphoric acid, perchloric acid, and aluminum chloride. Aluminum chloride is the catalyst with which this paper is concerned, and its history in relation to its influence on condensation reactions between alcohols and the benzene nuclei shall be considered. In 1897, Nef (1) condensed benzyl alcohol and benzene in the pre­ sence of aluminum chloride and obtained diphenyl methane. The work was repeated by Huston and Friedmann (S) and a thirty per cent yield of diphenyl methane was reported. Since Nef’s first condensation, many have been reported. Of the primary saturated aliphatic alcohols Huston and Sager (3) tried to condense methyl, ethyl, propyl, n-butyl, iso-butyl, and iso-amyl alcohols with benzene using aluminum chloride as a catalyst; no condensation was noted. Huston and Hsieh (4) repeated and extended this work, in place of benzene they used phenol, but no condensation was noted in either case. In the unsaturated primary aliphatic series, allyl alcohol gave a sixteen per cent yield of the condensation product with benzene (3) and also condensed with phenol (5). The aliphatic secondary alcohols condense with benzene giving yields of from twenty—five to thirty per cent. Huston and Hsieh (4) condensed isopropyl and secondary butyl alcohols as well as methyl 5 propyl and methyl isopropyl carbino-L.s with benzene. Tzukervanik and co-workers (6 ) report the condensation of simple secondary alsohols with benzene and toluene. At the present time, the condensations of isopropyl, secondary butyl, the secondary amyls, and the secondary hexyl alcohols with phenol are being studied in this laboratory by Monroe, Esterdahl, and Curtis. Tertiary aliphatic alcohols condense readily with both benzene (7) and phenol. Huston and Hsieh (4) condensed tertiary butyl, tertiary amyl, and tertiary hexyl alcohols with phenol, and Huston and Fox (8 ) extended this work to include benzene. Tzukervanik (6 ) reported the condensation of tertiary alcohols with benzene and toluene obtaining similar results. The tertiary heptyl alcohols were condensed with benzene by Huston and Binder (9) and with phenol by Huston and Hedrick (10). The condensation of tertiary octyl alcohols with benzene have been reported by various authors working under Hustonj namely, Schulati (11), Anderson (12), and Breining (13). Huston and Guile have con­ densed some tertiary dimethyl amyl carbinols with phenol (14). In the aromatic alcohols, Huston and Friedmann (2) condensed benzyl alcohol v.ith benzene and later Huston (15) extended this work using phenol, anisole, and phenetole in a similar manner. and Grotemut (16) condensed phenol with diphenyl carbinol. Huston, Lewis, YJhen the tertiary alcohol, triphenyl carbinol (17), was tried with benzene, only triphenyl methane was obtained. The mixed aliphatic-aromatic alcohols have been investigated by various workers. In the secondary alcohols, methyl phenyl and ethyl phenyl carbinols have been condensed v.ith benzene by Huston and 4 Friedmann (18) and with phenol by Huston, Lewis, and Grotemut (16). Of the tertiary dialkyl aryl carbinols, dimethyl phenyl, methyl ethyl phenyl, and diethyl phenyl carbinols have been investigated by Macomber (19), and Welsh and Drake (20) have reported the condensation of dimethyl phenyl carbinol with phenol. With the tertiary diaryl alkyl alcohols, ethyl diphenyl carbinol , Huston and Wilsey (21), propyl diphenyl and isopropyl diphenyl carbinols, Huston and Hradel (22), gave only unsaturated products of the alcohols when subject to condensation with benzene. V/elsh and Drake (20) reported the condensation of methyl diphenyl carbinol with phenol. At the present time, the condensation of ethyl diphenyl, propyl diphenyl, isopropyl diphenyl, n-butyl diphenyl, isobutyl diphenyl, secondary butyl diphenyl, tertiary butyl diphenyl, and n-amyl carbinols writh phenol is being investigated in this labora­ tory by Jackson. Other alcohols have been condensed with different compounds. Huston and co-workers (25) reported condensation of halogenated benzyl alcohols with halogenated phenols, cresols, and halogenated cresols. Huston and Goodemoot (24) condensed cyclobutyl, cyclopentyl, and cyclo— hexyl alcohols with benzene. 5 Theoretical Work done by Huston and co-workers indicates that in all conden­ sations between alcohols and aromatic hydrocarbons in the presence of aluminum chloride, the alpha carbon atom must be under strain. Thus, the hydroxyl group is activated due to the ionstable bond between the carbon and oxygen atom. This bond is present in allyl alcohol (A) and benzyl alcohol (B), both of which condense with ease. H. c:c:c.O;H H' ’ H^' ceHs: c:‘ o:H H^' A B The electron pair between carbon and oxygen is attracted strongly by both-atoms, forming the same type of bond as does a molecule of chlorine . ’Cl! C l ’ . which is unstable and very reactive. In the primary (C), secondary (D), and tertiary (E) alcohols, attention is riveted on the carbon to oxygen bond. Ha . :o :h H " r ;c C r R-aS :c :o:h H RR :c :o,:H R D E This bond is unstable in tertiary alcohols, less so in secondary, and fairly stable in primary alcohols. This fact is borne out in the ease of replacing the hydroxyl group by the halogen of a halogen acid sind also the ease of dehydration. Thus, the carbon to oxygen bond of tertiary alcohols can be compared to that found in a molecule of hydro­ gen chloride H :ci.’ which is highly reactive. In view of this, ter­ tiary alcohols should condense very readily due to the active hydroxyl 6 group* while secondary alcohols should condense less readily, and pri­ mary ones only under drastic conditions. A review of the literature shows this view to be true. To explain the path of reaction in condensations, several mechan­ isms have been advanced, but none conclusively established. The data accumulated is not always comparable, as different catalysts, tempera­ tures, and solvents were used. In discussing the mechanism, a tertiary alcohol will be used with the view that the same mechanism may or may not be similar for primary and secondary alcohols. Tzukervanik and Nazarova (£5) suggested a Friedel—Craft reaction in which the alkyl halide formed from the alcohol and aluminum chloride condensed with the hydrocarbon by means of the excess aluminum chloride present. Their scheme of reaction was as follows: I - (CH3 )3COH + aici 3 ---------»A1C12 0C(CH3 )3 + HC1 CH3 II - aici2 oc(ch3 )3 ----------- »ch3- 6 =ch 2 + A1C12 0H ch 3 III - CH3- 6 - C H 2 + H C 1 ------- K C H 3 )3C'C1 IV - (CH3)3 C-C1 + C 6H 6 -------- ►(CH3 )3 C-C0H8 + HC1 In criticizing this course, note that the presence of an aluminate is highly improbable, as it is not easy to replace the hydroxyl hydrogen of a tertiary alcohol. In addition, Hedrick (10) added the tertiary alcohol, normal butyl dimethyl carbinol, to aluminum chloride suspended in petroleum ether and noted that hydrogen cixloride was given off elmost instantaneously with the generation of heat. Thus, if Tzukervanik*s idea holds, no hydrogen chloride should be evolved and condensation should give a normal yield, but the yield also aas found to be much 7 smaller than in ordinary condensations. The dehydration of the alcohol to form an alkene was offered by McKenna and Sowa (26) as the path taken in condensations using boron trifluoride as the catalyst. For normal butyl alcohol the path is: V - CH 3CH2 CH2 CH2OH ------ EEa > CH3CH2CH = CH2 + H20 _ ch3 VI - CH3CH2CH = CH2 + CeH 5 ----“ ■«----> CH3 CH2'6HC 6H 5 It can be seen that normal and secondary alcohols give identical products as do iso— and tertiary alcohols. Zinc chloride is the catalyst used by McGreal and Niederal (27) who claim a like mechanism. Y/elsh and Drake (28) use this course to explain the condensation of aryl— substituted carbinols with phenol using aluminum chloride as a catalyst. Benzyl alcohol, benzhydrol, and triphenyl carbinol, which cannot dehydrate, split water off by loosing the hydroxyl group of the alcohol and a nuclear hydrogen of the phenol. Many workers (29) have reported condensations of unsaturated hydrocarbons with aromatic hydrocarbons using aluminum chloride as a catalyst. The work done favors the alkene—formation idea. In defeat of the alkene—formation course, there is little evi­ dence. It should be noticed that different catalysts and temperatures were employed from that of Huston's, who has shown that primary alco­ hols will not react with benzene in the presence of aluminum chloride under ordinary conditions. Another plausible mechanism is the formation of an ether of phenol followed by rearrangement into the substituted phenol. Smith 8 (50) reported the rearrangement of m-cresyl isopropyl ether, tertiary butyl— , isobutyl— , secondary butyl— , isopropyl—phenyl ethers and p— cresyl isobutyl ethers when treated in the cold with eaual molecular amounts of aluminum chloride. Others (31) have reported ether re­ arrangements in a similar manner. Thus, if the ether was formed in the reaction, it might rearrange into alkyl phenols. Merz and Weith (52) did report a yield of 10 - 12 per cent of diphenyl ether from aluminum chloride and phenol at reflux temperature. Niewland (35) obtained ethers and substituted ethers, using boron fluoride with phenol and methyl, ethyl and isopropyl alcohols. Claisen (34) has pointed out that in alkylating the alkali salt of phenol with a halide of an unsaturated alkene; the ether is not a necessary intermediate, for phenyl alkyl ethers, under the conditions of formation, do not rearrange to alkyl phenols. Furthermore, Huston has reported good yields in the condensation of tertiary alcohols and benzene, anisole, and m—cresyl methyl ether (4) and the condensation of benzyl alcohol with anisole and phenetole (15) in which reactions there is no possibility of ether formation. Xn this laboratory (3 5 ) work was started on a mechanism for aluminum chloride condensations based on addition products between aluminum chloride, alcohol, and phenol. The idea is not new, as addition products with aluminum chloride (36) have been reported as well as with other catalysts (37). The theory is that a complex molecule is formed between the outer shells of electrons of aluminum chloride and the reacting substances. The compound formed is not 9 stable and rearranges to give other compounds or its starting products according to the reacting compounds and the conditions under which the experiment takes place. conclusions. The theory is still too vague to draw definite 10 Experimental Data Materials Magnesium turnings especially- prepared for Grignard reactions were used after drying in an oven at 40°C for several days. Benzene was thiophene free, C.P. grade. Petroleum ether, B.P. SO—G5°C. Acetone was dried over sodium sulfate and was of C.P. grade. Methyl ethyl ketone was dried over sodium sulfate and was of C.P. grade. Phenol was Mallinckrodt1s (crystals). Aluminum chloride was I.Ierck’s Reagent white anhydrous sublimed. Diethyl ether was anhydrous for Grignard reactions. Bromobenzene was made from bromine and benzene, B.P. 153°C. Diethyl ketone was prepared by the oxidation of Eastman’s diethyl carbinol using potassium dichromate and sulfuric acid (25), B.P. 101102°C. P-bromo anisole was prepared by the bromination of anisole, B.P. 252—235°C. 11 Dimethvlphenvl Carbinol In a dry, three-liter, three-necked, round-bottom flask fitted with a rubber-sealed stirrer, a reflux condenser with calcium chloride tube attached, and dropping funnel were placed 50 grams (2 moles) of magnesium turnings, a crystal of iodine, 100 ml. of anhydrous diethyl ether, and 14 grams of bromobenzene. The reaction started automatically and was externally cooled if too violent. After the reaction had subsided, the stirrer was started and a mix­ ture of 300 grams of bromobenzene (Total-2 moles) and one liter of an­ hydrous ether was run in at such a rate that the reaction mixture refluxed gently. When the addition was completed (about 4 hours), the mixture was stirred for two hours. To the reacted mixture was added 120 grams (2 moles) of acetone dissolved in 200 ml. of anhydrous ether: added fast enough to cause gentle refluxing. it was The resulting solution was stirred for two hours and then poured on cracked ice. The precipitate was dissolved by the addition of dilute hydrochloric acid. The ether layer was separated and the water layer was extracted once with ether. The combined ether layers were washed twice with water and then dried with anhydrous sodium sulfate. The ether was removed under reduced pressure and the resulting liquid was fractionated (no column) using an oil bath. Yield: B.P. 220 grams 77 93 - (81$). 78°C/ 3 mm. bath 115°C 94°C/l3 mm. bath 130°C 177 - 179°C/737 mm. decomposes Checks were obtained on physical constants as recorded in the 12 literature. This alcohol was previously prepared by Klages (38), Stephens (39), and Rotbart (40). Methvlethvlphenyl Carbinol The above method was used except that the acetone was replaced by 144 grams (2 moles) of methyl ethyl ketone. B.P. 83 - 84°G at Yield: 250 grams (83%). 2 mm. bath 115°C 98 — 99°C at 13 mm. bath 135°C 198 — 199°Cat 742 mm. decomposes Klages (41), Tiffeneau (42), Inglis (43), and McKenzie and Ritchie (44) have prepared this alcohol. Diethvlphenvl Carbinol This alcohol was prepared by the same method using 172 grams (2 moles) diethyl ketone in place of the acetone. B.P. 93 - 94°C at Yield: 214 grams (65%). 2 mm. bath 140°C 103 - 104°Cat 13 mm. bath 150°C 220 — 223°Cat 738 mm. decomposes This alcohol contains slight impurities of diphenyl. weretried, such as, ethyl benzoate with ethyl bromide, but this contain­ ed ethylbenzoate; benzoyl acid as the impurity. Other methods chloride with ethyl bromide gave benzoic Due to the fact that the alcohol splits off water readily (even on standing), no method was found to remove these slight impurities. Many methods have been used to prepare this alcohol. who reported the work are: The authors Grignard (45); Bayer and Company (46); Kling A 13 (47); Klages (48); Schoringin (49), and Gilmaro (50), 14 Condensations In view of the fact that all condensations were carried out in a similar manner, only a typical run is described. A. Condensations with Benzene In a 500 ml., three-necked, round-bottom flask fitted with a stirrer, calcium chloride tube, and a dropping funnel were placed 98 grams (1.25 moles) of benzene and 17.3 grams (0.13 moles) of anhydrous aluminum chloride. 34 grams (0.25 moles) of dimethylphenyl carbinol was added dropwise to the stirred suspension. The temperature was kept between 25—30°C, using a water bath when necessary. The color changed to a deep reddish-brown and generally hydrogen chloride was given off during the addition. The mixture was stirred for an additional three hours and then allowed to stand overnight. The mixture was then de­ composed by means of a crushed ice—hydrochloric acid solution (1 :1 ). After separating and washing the water layer twice with benzene, the benzene layers were united, washed once with water, dried over calcium chloride, and placed on a steam bath to remove the solvent. The resi­ due was distilled under reduced pressure using a modified Claisen (12-inch column, l/2 -inch bore). In some cases no column was used for the higher fractions. Condensations: A. Dimethylphenyl Carbinol, Benzene, and Aluminum Chloride 34 grams — 0.25 moles — carbinol 98 grams -1.25 moles - benzene 17 grams - 0.13 moles - aluminum chloride 15 Fractions: B. - 110°C/2 mm. 4 grams Diphenyl (2 ml. undetermined liquid) 110 - 115°C/2 mm. 4 grams 2 , 2-diphenyl propane (8 .2 /6) 115 - 120°C/2 mm. 4 grams 1, 1 , 5-trimethyl—5—phenyl indan 120 - 150°C/2 mm. 9 grams 1, 1, 5-trimethyl—5—phenyl indan 150 - 155°C/2 mm. 4.5 grams 4—methyl—2, 4-diphenyl-2-pentene 155 - 180°C/2 mm. 4 grams 4-methyl—2, 4—diphenyl-2-pentene Above 180°C/2 mm. 1 gram Tar Methylethylphenyl Carbinol, Benzene, and Aluminum Chloride 58 grams - 0.25 mole — carbinol 98 grams — 1.25 moles - benzene 17 grams - 0.15 mole — aluminum chloride Fractions: 58°C/2 ram. 4 grams 2 -phenyl butane 58 - 117°C/2 ram. 5 grams Diphenyl (1 ml. undetermined liquid) 117 - 122°C/2 mm. 6 grams 2, 2-diphenyl butane (11.556) 122 - 150°C/2 mm. 15 grams 1, 2, 5-trimethyl-l-ethyl-5-phenyl indan Above 150°C/2 mm. 5 grams Tar 57 - Diethylphenyl Carbinol, Benzene, and Aluminum Chloride 41 grams — 0.25 mole 98 grams - carbinol 1.25 moles - benzene 17 grams — 0.15 mole - aluminum chloride Fractions: 90 grams Benzene - 72°C/l2 mm. 72 - 80°C/l2 mm. 4 .5 grams 5 -phenyl pentane 80 - 110°C/12 mm. 5.5 grams 5 -phenyl-2 -pentene 4 16 110 - 160°C/l2 mm. 3.0 grams 1,1, 160 - 190°C/12 mm. 4.0 grams 1, 1, 3-triethyl-2-methyl-3-phenyl indan(?) 190 - 210°C/12 mm. 12.0 grams 1, 1, 3-triethyl-2-methyl-3-phenyl indan(?) 10.0 grams 1, Above 210°C/l2 mm. B. 3-triethyl-2-methyl-3-phenyl indan(?) 1, 3—triethyl—2—methyl—3—phenyl indan(?) Condensations with Phenol As with benzene the condensations here carried out are in the same manner, only the benzene was replaced by phenol dissolved in petroleum ether. Condensations: A. Dimethylphenyl Carbinol, Phenol, and Aluminum Chloride 68 grams - 0.5 mole - carbinol 57 grams — 0.6 mole — phenol 34 grams - 0.25 mole - aluminum chloride 100 ml. — petroleum ether Fractions: - 90°C/l2 mm. Phenol 80 - 115°C/ 2mm. 0.5 gram Diphenyl (l/3 ml. undetermined liquid) 115 - 125°C/ 2mm. 4.0 grams 1, 1, 3-trimethyl-3-phenyl indan 125 - 140°C/ 2 mm. 0.0 grams 140 - 160°C/ 2 mm. 82.0 grams Above 160°C/ 2mm. B. 20.0 grams 2.0 grams P-(oc,^-dimethyl benzyl)-phenol (77%) Tar Methylethylphenyl Carbinol, Phenol, and Aluminum Chloride 38 grams — 0.25 mole — carbinol 28 grams — 0.30 mole — phenol 9 grams - 0.068 mole - aluminum chloride 50 ml. — petroleum ether 17 Fractions: - 90°C/12 mm. 6.0 grams Phenol 58 — 65°C/ 2 mm. 1.0 gram 2 -phenyl—2-butene 65 — 90°C/ 2 mm. 2.0 grams Diphenyl 90 - 140°C/ 2 mm. 0.0 grams 140 - 170°C/ 2 mm. 4.5 grams P- Above 170°C/ 2 mm. 5.0 grams Tar -methyl-«c-ethyl benzyl)-phenol Diethylphenyl Carbinol, Phenol, and Aluminum Chloride 41 grams - 0.25 mole — carbinol 28 grams - 0.50 mole - phenol 17 grams - 0.125 mole - aluminum chloride 100 m l . - petroleum ether Fractions: - 70°C/l2 mm. 3.0 grams Phenol 70 - 80°C/ 2 mm. 3.5 grams 3-phenyl pentane 80 - 100°C/ 2 mm. 2.0 grams 3-phenyl—2-pentene 100 - 150°C/ 2 mm. occasionally 150 - 165°C/ 2 mm. 41.0 grams Diphenyl p-(o^joc-diethyl benzyl)-phenol (68$ • 165 - 195°C/ 2 mm. 0.0 grams Above 195°C/ 2 mm. 4.0 grams Tar 4 Identification The liquids were distilled until at least a three-degree fraction was obtained. In almost all cases, this constituted about ninety per cent of the main fraction under observation. The solids were subject to crystallization until a constant melting point was obtained from two different solvents. Diphenyl Found in the carbinols and in some condensations due to the reac­ tion between bromobenzene and phenyl magnesium bromide. M.P. 68 - 69°C (Handbook: 69 - 70°C) 2 -phenyl-butane Prepared and recorded in the literature by Schramm (51), Estreicher (52), Klages (55), and Levene and Marker (54). B.P. 37 - 38°C/ 2 mm./80°C 55 - 55°C/l2 mm./lOO°C 165 - 166°C/740 mm. D|° = 0.8640 (Dfi = 0.8634 - Klages) n ®5 = 1.4880 (nf)5 = 1*4878 - Levene) Bromination using iron as a catalyst giving 2-(P-bromo phenyl)-butane. B.P. 221 - 224°C/745 mm. (235 - 237°C/739 mm. - Schramm) 2 —ohenvl—2 -butene B.P. 55 - 57°C/ 2 mm./95°C 72 - 74°C/l2 mm./H0°C 183 - 185°C/747 mm. Reduced to 2-phenyl butane using sodium and ethyl alcohol. 19 B.P. 170 — 171°C/745 mm. — Klages (5 3 ) Perrot (55) and Tiffeneau (42) also describe this compound. 5—phenyl—pentane Described by Klages (48), Spath (56), Luginin (57), Dafert (58), and Levone (54). B.P. 50 — 53°C/ 2 rnm./90°C 74 - 76°C/l2 mm./llO°C 186 - 187°C/740 mm. Prepared by two different methods: 1. Friedel—Grafts Reaction: Fifty grams of 3-bromopentane and 150 grams of benzene were placed in a three-necked, 500 ml., round-bottom flask fitted with a stirrer, reflux condenser, and calcium chloride tube. chloride were added slowly while stirring. Ten grams of aluminum After addition, it was allowed to stir for three hours and then decomposed by the usual method. B.P. 2. 50 — 53°C/ 2 ram. Yield: 20 grams (40%) Grignard Reaction: This was run on 157 grams of bromobenzene, 27 grams of magnesium, and one liter of benzene as the solvent. 151 grams of 3-bromopentane was added and the mixture refluxed five hours. It was decomposed in the usual manner. B.P. 50 - 53°C/ 2 mm. Yield: 15 grams (10^) All three compounds were brominated as follows: Eight grams in ice, 0.9 gram ofthe compound and a pinch of powdered iron wascooled ofbromine was addeddropwise with shaking. After set­ ting two days, the solution was taken up in ether, v.rashed with water, 20 and dilute sodium carbonate, dried, and distilled. B.P. 116 - 118°C/72 mm. Yield: (42%) 240 - 242°C/738 mm. % bromine from condensation fraction: 35.20 (found) 35.17 (calculated) The compound is 3— (P—bromo phenyl)-pentane. Proof: One gram of the above compound and twenty ml. of 6 N nitric acid were sealed in a Carius tube and heated twenty hours at 180°C. A solid resulted having a M.P. of 249°C, which was P—bromobenzoic acid (M.P. 251 253°C). 5—phenyl— 2 -pentene B.P. 63 - 65°C/ 2 mm./H0°C 82 — 84°C/l2 mm./l25°C 202 - 204°C/750 mm. Nitroso chloride, M.P. 114°C % chlorine (M.P. 117°C — Klages) 16.60 (found) 16.75 (calculated) Reduced to 3—phenyl—pentane, B.P. 186 — 188°C/740 mm. Found in the literature under Klages (48), Grignard (59), and Tiffeneau (42). 2. B.P. 2 —diphenyl—propane 95 - 96°C/ 2 mm. 139 - 140°C/l2 mm. 280 - 283°C/734 mm. < 21 D £5 _ 0.9956 (Df5 = 0.9958 - Sabatier) n4 “ 1*568 (njp5 = 1.570 — Sabatier) y 2S = 29.12 Compound did not solidify as stated by Sabatier (60), but reacted as stated by Silva (61). 2 . 2 -diphenvl-butane B.P. 118 M.P. 127°C — 119°C/ 2 mm. As described by Zincke (62). P— ( oC-dimethyl ben zyl)—phenol B.P. M.P. 152 - 155°C/ 2 mm. 73°C Aryloxy acetic acid, M.P. 116°C (M.P. 117°C - Welsh). Synthesised in patents (63), (64), and synthesised and proven by Welsh and Drake (20). 4-methyl-2. 4—diphenyl—2—pentene B.P. 168 - 169°C/l2 mm./215°C M.P. 130 - 131°C Two and one-half grams of the compound, 6 grams of aluminum chloride, and 100 ml. of benzene were mixed together and shaken frequently during the course of four days. It was then decomposed by ice and dilute hydro­ chloric acid and the benzene layer evaporated. A solid, M.P. 50 - 51°C, resulted, which is 1, 1, 3-trimethyl-3phenyl indan (see below) according to Bergmann (65). Bogert and Davidson also refer to this compound (6 6 ). ( 22 1. 1. 5—trimethvl-5—phenyl—indan B.P. 163 - 165°C/24 mm. 305 - 306°C/734 mm. M.P. 51 - 52°C This data agrees with the compound described by Bergmann (65) and Bogert and Davidson (6 6 ) as well as that of Welsh and Drake (20). 23 Proof of Structure P- (^-methyl-oc-ethvl benzyl)-Phenol The chloride of methyl ethyl phenyl carbinol was prepared, accord­ ing to Klages (48), with great difficulty. The carbinol was saturated with dry hydrogen chloride and allowed to stand in an ice box for one day, the water separated, and the saturated carbinol dried with calcium chloride; the process was repeated three times. The chloride was dried again by shaking it with anhydrous sodium carbonate for two minutes and the resulting solution was distilled under vacuum. The boiling point of the chloride was 78°C/ 2 mm. Seven grams of magnesium turnings and 20 ml. of anhydrous ether were put in a three-necked, three-liter, round-bottom flask provided with a reflux condenser with calcium chloride tube attached, a stirrer, and a separatory funnel. Five grams of P-bromo-anisole was added and heat applied until the reaction started, when 45 grams of the P-bromoanisole, dissolved in 100 ml. of ether, was run in at such a rate that the solution refluxed. three hours: After addition, the solution was stirred for forty—six grams of the chloride of methyl ethyl phenyl carbinol dissolved in 100 ml. of ether was run in fast enough to cause refluxing. After the addition, the ether was removed by distillation, one liter of anhydrous benzene was added and the solution was refluxed one day on a water bath. Xt was then decomposed by dilute hydrochloric acid and ice, the benzene layer separated, washed with water, the sol­ vent removed on a steam bath and the resulting solution distilled under vacuum. The methyl ether of P— (®<—methyl—«?-ethyl benzyl)—phenol thus 24 prepared boiled at 140-142°C/ 2 mm. Yield: 15 grams (23$). The 15 grams of* methyl ether of* P— («c—methyl—oc-ethyl benzyl)—phenol were refluxed with 100 grams of phenol and 50 ml. of 48$ hydrobromic acid for four hours. Thesolution was separated from the water layer, washed with water until neutral, and distilled. After the phenol was removed, the remaining P-(of—methyl-o<-ethyl benzyl)-phenol came over at 147—148°C/ 2 mm. Yield: 8 grams (57$). Carbon and Hydrogen % Carbon % Hydrogen 84.43 7.99 Found Calculated 84.91 8.01 Benzoyl ester M.P. 55°C (benzene) Methyl ether B.P. 140-142°C/ 2 mm./l85°C Mixed melting points with the benzoyl ester of P-(«<-methyl-o<^-ethyl benzyl)-phenol, obtained from the condensation of methyl ethyl phenyl carbinol with phenol, gave no depression of the melting point. The methyl ether of P- (c-c-methyl-eC-ethyl benzyl)-phenol, obtained from the condensation of methyl ethyl phenyl carbinol with phenol, boil­ ed at 140—141°C/ 2 mm./l85°C. Physical Constants of P-^c-methyl-«c-ethyl benzyl)-Phenol B.P. 147—149°C/ 2 mm./215°C 196—197°C/l2 mm. 318°C/740 mm. a25 = 1.062 n2 S = 1.5810 4 4 y25 = 30.99 Molecular Weight 25 Found 250.0 Calculated 226.50 Carbon, and Hydrogen % Carbon % Hydrogen 84.82 7.99 Found Calculated 84.91 Benzoyl ester 8.01 M.P. 55-56°C Carbon and Hydrogen % Carbon % Hydrogen 85.62 5.95 Found Calculated 85.60 Methyl ether 6.71 B.P. 140-141°C/ 2mm./l35°C McGreal and Niederal (27) prepared this compound but gave no de­ finite proof of its structure. P— (°c. -diethyl benzyl)—Phenol The method used in the preparation of P-(oc-methyl-°c-ethyl benzyl)phenol was also used in the synthesis of this compound. Eleven grams of magnesium turnings, 85 grams of P—bromo—anisole and 85 grams of the chloride of diethyl phenyl carbinol were used to prepare the methyl ether of P-O*^, Yield: -diethyl benzyl)-phenol, which boiled at 155-158°C/ 2 mm. 20 grams (17.5^). In changing the methyl ether to the phenol, a yield of 12 grams (65.5^) was obtained. Found Calculated B.P. 142-145°C/ 2 mm. Carbon and Hydrogen % Carbon % Hydrogen 84 •92 8 •49 84.95 8.38 Methyl ether B.P. 135—138°C/ 2 mm. Benzoyl ester M.P. 99.5—100°C (benzene) 26 Phenyl urethane M.P. 112°C (ligroin) Mixed melting points with the same derivatives of the phenol from the condensation of diethyl phenyl carbinol with phenol gave no depres­ sion of the melting point. Physical Constants of P-( ch3-ch2- 6 The 140—145°C fraction from the above preparation was dissolved in 50 ml, of dry benzene and 20 grams of aluminum chloride added. The suspension was allowed to stand for a week with frequent shaking, then it was decomposed with ice and hydrochloric acid, and distilled. 126-130°C/ 2 mm. Yield; 10 grams. B.P. This compound was thought to be 1, 2, 3—trimethyl—1—ethyl—5—phenyl indans 9K3 — C-C2H 5 H-C-CH3 + AICI 3 HO-C "CH3 c»h5 it agreed in boiling point and stability towards oxidation with the dimer isolated in the methyl ethyl phenyl carbinol condensation with benzene, but differed in nitration and spectrographic behavior. This compound when nitrated did not form a solid nitro derivative. Physical Constants of the Dimer Isolated in the Methyl Ethyl Phenyl Carbinol Condensation with Benzene B.P. 127—129°C/ 2 mm. 180—182°C/l2 mm. 321°C/738 mm d* n* = 0.996 g 25 = 27.03 Molecular Weight Found 264 Calculated 264.39 = 1.5646 Found Carbon and Hydrogen % Carbon % Hydrogen 90.40 9.01 Calculated 90.85 Nitro derivatives 9.14 M.P. 192.5-193°C, 232°C Nitration of the dimer from the methyl ethyl phenyl carbinol condensation with benzene was brought about by mixing 3 grams of the compound with 7 ml. of concentrated nitric acid and 5 ml. of concen­ trated sulfuric acid and then heating for a half hour at 50°C while shaking. The mixture then was poured into water, filtered, and the solid recrystallised from ether. M.P. 192.5-195°C. Nitration, using fuming nitric acid without the aid of sulfuric acid, gave a solid. M.P. 232°C. Oxidation of the dimer with alkaline permanganate was attempted. Eight grams of the dimer, 70 grams of potassium permanganate, and 6 grams of potassium hydroxide were added to 100 ml. of water and the resulting solution was allowed to stand on the steam bath for one month, but the dimer v/as recovered unchanged. Synthesis of 1. 1. 5-triethvi-£-methyi-5-phenyl indan The ethyl ester of 3-hydroxy-2-methyl-3-ethyl pentanoic acid was prepared by means of a reaction by Reformatski according to Armond, Kon, and Leton's procedure (6 8 ). Two hundred grams of di­ ethyl ketone, 370 grams of the ethyl ester of“^-bromo propionic acid, 130 grams of zinc and 200 ml. of benzene were placed in a three—necked, three—liter, round—bottom flask fitted with a stirrer and reflux condenser with calcium chloride tube attached. The reaction 30 was kept cool by the use of cold water on the outside of the flask. After the reaction had slowed down, the mixture was heated until almost all of the zinc had disappeared. It was then poured on cracked ice and decomposed with hydrochloric acid. The oily layer was washed three times with water, dried over calcium chloride, and distilled. 100°C/l4 mm. Yield: B.P. 95- 65 grams. C00C2H5 + Zn -frytirolyaed * C2H5-C 6 - COOCoH, The ester was refluxed for an hour with 60 grams of acetic anhy­ dride, separated from it, washed once with water, and poured into 500 ml. of 5% alcoholic potassium hydroxide. The resulting solution was refluxed two hours and then poured into 500 ml. of water. The water solution was made acid with hydrochloric acid and extracted three times with ether. distilled. 9H The ether layer was then evaporated on the steam bath and B.P. 120—124°C/l2 mm. Yield: ¥ > c2h5-c = c — cooc2h5 + h2o c2h5 ch3 c2h5-<} — 9 — cooc2 h5 + (ch3co)2o c2h5 ch3 C2H5-C =■ C — COOCgHs + ale. K0H 62h 5 c h 3 47 grams. flsidify -> c2h5-c = c — C00H + C2H50H c2hs 6h3 The 2-methyl-5-ethyl—2-pentenoic acid was convei’ted to 4-methyl5-ethyl—4—hepten-3—c*e using the method described by Kon and Leton (68). Fifty grams of thionyl chloride was used to convert the acid to the chloride and the chloride was then run into an ether solution of ethyl magnesium bromide made from 9.5 grams of magnesium, 40 grams of ethyl bromide and 200 ml. of anhydrous ether. the usual manner. B.P. 82—84°C/l2 mm. The Grignard was decomposed in Yield: 30 grams. 51 C2Hs-C — 9 COOH + SOCl2-------- ► C2Hs-C = C — GOC1 + SOo + HC1 c 2h 5 c h 3 62h 5 c h 3 G2Hs~9 — 9 g 2h 5 c h 3 0001 + C2H5 MgBr — »C2H5-9 = C — COC2H5 CgH5 £H s The unsaturated ketone was dissolved in 500 ml. of anhydrous ben­ zene and, while stirring, 35 grains of aluminum chloride were added. The solution was stirred two hours and allowed to stand for a week. It was then decomposed in the usual manner and distilled. 120°C/ 2 mm. Yield: B.P. 110- 37 grams. £2^ 5-9 '— 9 goc2h5 + c6h6 + AICI3 c 2h 5 c h 3 > C6H s H c2h5-6--- 6 — coc2h5 <52h 5 6h 3 The 4—methyl—5—ethyl—5-phenyl-3-heptanone from the above prep­ aration was dissolved in 100 ml. of anhydrous ether and dropped into an ether solution of phenyl magnesium bromide prepared from 40 grams of phenyl bromide, 8 grams of magnesium, and 200 ml. of anhydrous ether. The reaction was decomposed with ice and hydrochloric acid and, after removal of the benzene, v:as distilled. 2 mm. Yield: B.P. 130—155°C/ 30 grams. C6H5 H c2h5-c — c — coc2h5 + ceH5MgBr 62h 5 6h 3 , , . hydrolyzed— 9 o H5 H c 6h 5 » c2h5- 9 -— c — c - c2hs c sh 5 c h 3 o h The above alcohol was dissolved in 50 ml. of benzene and 15 grams of aluminum chloride added. The mixture was shaken frequently during the course of a week; then decomposed by ice and hydrochloric acia, and distilled. B.P. 138-140°C/ 2 mm. Yield: 14 grams. 32 9 2 hs ^ N c-c2 h 5 H^c-CH3 H0 “9 -c2 h5 6 5 ^ + AICI3 ----- ► c2hs ^ c®h5 HpC-CHa CqH5 This compound showed the same boiling point and stability towards oxidation with the dimer isolated in the diethyl phenyl carbinol con­ densation with benzene, but did not behave the same toward nitric acid. A different attempt was made to synthesize the dimer, using the same idea as before but following a different procedure. A Reformat ski Reaction was run on 290 grams of phenyl ethyl ketone, 370 grams of the ethyl ester of®c-bromo propionic acid, 150 grams of zinc, and 200 ml. of benzene, and the fraction between 130—140°C/l2 mm. was collected. Yield: 70 grams. The ethyl ester of 3—hydroxy—2—methyl—3—phenyl pentanoic acid from the Reformatski was run into an ether solution of ethyl magnesium bromide prepared from 20 grams of magnesium, 80 grams of ethyl bromide and 200 ml. of anhydrous ether. ner. The Grignard was decomposed in the usual man­ The 120—125°C/ 2 mm. fraction was collected and weighed 15 grams. c2h5- c — oh c — cooc2h5 + 2C2 H5MgBr ch3 hyflrotoefl » c2h5-c -— oh c-— c — ch3 6h c2h5 The 3, 5 —dihydroxy—4—methyl—3—ethyl—5-phenyl heptane so prepared was dissolved in 200 ml. of benzene and 30 grams of aluminum chloride added; shaking. the solution was allowed to stand for one week with frequent It was decomposed with ice and hydrochloric acid and after re­ moval of the benzene layer, distilled. B.P. 137—141°C/ 2 mm. Yield: 8 grams. c2 h5 ^6^5 h C2 Hg ^ A „ XT A 0 — c-— c2hs + c6h6 + aici3 ---- » c2h5-c — 6Ho oh oh OH ?2^5 q — c — c2h5 + h2o ch3 CeH 5 5 5 5 V2H5 35 J ? 2S5h -C-C2 HS h^c-ch3 H0 'C^c2 h 5 fi 5 + AICI3 --------- * 92Hs f-- >-----C-C2H 5 I h-c-ch3 + h2o W - 9 ^ 2h 5 V CeHs This compound was not the same as the dimer isolated from the di­ ethyl phenyl carbinol condensation with benzene, but it was comparable to the compound described above. Physical Constants of the Dimer Isolated from the Diethyl Phenyl Carbinol Condensation with Benzene B.P. 139—140°C/ 2 mm./220°C 195-197°C/'l2 mm. 338°C/740 mm. dj5 = 1.000 n |5 = 1.5670 ar2S = 27.03 Molecular Weight Found 291 Calculated 292.44 Carbon and Hydrogen % Carbon % Hydrogen Found 90.33 9.40 Calculated 90.35 9.65 Nitration of the dimer, using a mixture of nitric and sulfuric acids, as well as fuming nitric acid, did not give a solid compound. Oxidation of the dimer with alkaline permanganate did not occur, for it was recovered unchanged as in the dimer from the methyl eohyl phenyl carbinol condensation with benzene. 34 Discussion The procedure used in this work consisted of the preparation of di­ methyl, methyl ethyl, and diethyl phenyl carbinols followed by their condensation with both benzene and phenol: all resulting products of the reactions were analyzed in order to identify them. The alcohols thus used were prepared from phenyl magnesium bromide and the ketone corresponding to the carbinol. A detailed description of their preparation, along with their constants and a review of the literature, has been given in the "Experimental" portion of this thesis. The condensations with benzene were carried out by mixing one equivalent of the carbinol with five equivalents of benzene, stirring, and gradually adding one—half equivalent of aluminum chloride; addition taking place in such a manner that the temperature was maintained between 25—30oC. The mixture was stirred for four hours, all owed to stand over­ night, and then decomposed with ice and hydrochloric acid. The benzene layer was then fractionally distilled and all fractions collected. The condensations with phenol were run in the same manner, but one and two—tenths equivalents of phenol were used in place of the benzene, and petroleum ether was used as a solvent. At first, crude fractions with a wide range of boiling points were taken and these fractions then worked upon until fractions of a three to five degree range were obtained. In most cases, the last fraction contained ninety per cent of the original wide-range fraction. The distilling was done either at 2 mm. or 12 mm. pressure followed by boiling point determinations at atmospheric pressure. 35 The f2ra.cbj.0 ns contained reasonably pure compounds. They were i— dentified, in most cases, by comparison with those already known. The comparison consisted of their physical constants and often certain derivatives were made. In four cases, the compounds had never been made: two of these four compounds were synthesized and their structures es­ tablished during the course of this work, but the other two are as yet unidentified. From the condensation of dimethyl phenyl carbinol with benzene was isolated the condensation product, 2, 2-diphenyl propane. compounds were also isolated. Two other These proved to be an unsaturated and a saturated dimer, namely, 4-methyl—2, 4-diphenyl-2-pentene and 1, 1, 3trimethyl-5-phenyl indan. CH3 c 6h5- 6 — OH ch3 The method of their synthesis probably was: A1C1, * csh 5-6 = ch2 + h2o ch3 ch3 c 6h 5- 6 = 9H 2 + II c6h5~ c- ch3 AlCla The methyl ethyl phenyl carbinol condensation with benzene gave 2-phenyl butane, 2 , 2 -diphenyl butane, the condensation product, and a dimer which was believed to be 1 , 2 , 3—trimethyl—1 —ethyl—3—phenyl indan, whereas, the diethyl phenyl carbinol reaction gave 3-phenyl pentane, 3phenyl—2 —pentene, and a dimer, but no condensation product. 36 In the phenol condensation series , dimethyl phenyl carbinol gave the saturated dimer 1, 1 , 3-trimethyl-3-phenyl indan and the condensa­ tion product P— (=<, ®C—dimethyl—benzyl)—phenol. This reaction had already been run by Welsh and Drake (20) who used a different method. The con­ densation, using methyl ethyl phenyl carbinol, gave 2 -phenyl-2 -butene and P— (<—methyl-oQ-ethyl benzyl)-phenol, the condensation. The unsatu­ rated compound, 3-phenyl-2-pentene, was isolated in the diethyl phenyl carbinol condensation, along with the saturated compound 3—phenyl pentane. The condensation, P— (<<, c<-diethyl benzyl)—phenol, was also obtained. P— (k -methyl—oC-ethyl benzyl)—phenol was presumably prepared by McGreal and Niederal (27), but not a great deal of proof was offered. In the present work the proof of P— (*—methyl-®Q-ethyl benzyl)-phenol was run according to Welsh and Drakefs method (20) . The chloride of methyl ethyl phenyl carbinol was made by saturating 2 -phenyl—2 -pentene with hydrogen chloride. The chloride was reacted with P—anisyl magnesium bromide in dry benzene. The resulting ether was decomposed by reflux— ing with phenol and hydro bromic acid, giving rise to P— ethyl benzyl)—phenol. —methyl—cx^- The equations for the reactions are: ch3 ch3 CH3- 0 -C6H4"MgBr + Cl-CC 6H 5 ---- > CH 3~ 0 -C6H4 -C C6H 5 + MgClBr c2 h5 c2 h 5 ch3 ch3 CHa-OGftH^C C 6H 5 + HBr ------- > H0-C6H4- C ---- CaHs + CH3Br C 2H 5 C2 Hs The P-(«<, oc-diethyl benzyl)-phenol was proven in the same way as p_(x-methyl-oQ-ethyl benzyl)-phenol, using the chloride of diethyl phenyl carbinol. This chloride was hard to obtain as it readily split off hydrogen chloride when distilled. It was used immediately without 37 distilling, after being dried with sodium sulfate for a short time. Attempts were made to synthesize the compound in the 122—150°C fraction of the methyl ethyl phenyl carbinol condensation with ben­ zene, as well as the 110-190°C fraction of diethyl phenyl carbinol condensation with benzene, but such attempts were futile. In view of the fact that an indan was identified in the dimethyl phenyl carbinol condensation with benzene along with 2 —phenyl propene, it appeared reasonable that an indan should also be isolated in the other two cases. The formation of the indan should take place for the methyl ethyl phenyl carbinol condensation as follows: CH3 C = £H-CH3 9h3 Aici — — ch3 9 — ch2-ch 3 c-ch3 Thus, the compound can be 1, 2, 5—trimethyl—1 —ethyl—3—phenyl indan: its molecular weight, as well as its carbon and hydrogen analysis, agree with this dimer. The attempted synthesis followed along the lines of the procedure that Bergmann (65) used in synthesizing the dimethyl phenyl carbinol indan. Homomesitone reacted with benzene in the pre­ sence of aluminum chloride: the resulting ketone then reacted with phenyl magnesium bromide and, presumably, 3, 4—dimethyl—2, 4 —diphenyl— 2-hexanol was obtained. This compound was then treated with aluminum chloride to obtain the indan, but the resulting compound did not compare 58 with the compound isolated from the condensations. The equations for the process ares CH3-CH2- C = C 9*H 5 C-CH3 + G s H6 + A1CI h Q + A1C1 The compound from the diethyl phenyl carbinol condensation with benzene was believed to be 1, 1, 3—triethyl—2-methyl—3—phenyl indan. Its synthesis was attempted using the same method as that of the methyl ethyl phenyl carbinol condensation, but the polymerization product of diethyl ketone was used instead of methyl ethyl ketone. The ketone, 4—methyl—5—ethyl—4—hepten—3—one, was made according to Kon and Leton (6 8 ) and reacted with benzene in the presence of aluminum chloride: the resulting ketone then reacted with phenyl magnesium bromide and 4—methyl 5—ethyl—3, 5—diphenyl—3—heptanol was believed produced. This alcohol was treated with aluminum chloride to obtain the indan5 however, the product obtained after synthesis was not the same as tnat from the di­ ethyl phenyl carbinol condensation. A different approach to the above synthesis was attempted by sub­ stituting phenyl ethyl ketone for diethyl ketone, along with other changes in the reactions. The procedure was: 39 H CoHs-C 0 + jjjk QJJ C00C2H 5 + Zn 3 JJ hvdrolyzed ^ c6H5-(i'---6 -— C00C2H5 + ZnBrOH g2h5 6h3 9H ? 1 -j . OH H OH C6H5 -Cc- C00C2H5 + 2C2HsMgBr -^Tdrolyzed > c6H^-9---C-— C --- C2H5 + MgBrOH C2 HS ch3 c2h5 ch3 c2h 5